U.S. patent application number 11/051724 was filed with the patent office on 2006-03-23 for therapeutic polypeptides, nucleic acids encoding same, and methods of use.
This patent application is currently assigned to CuraGen Corporation. Invention is credited to David W. Anderson, Jason C. Baumgartner, Ferenc L. Boldog, Stacie J. Casman, Shlomit R. Edinger, Esha A. Gangolli, Valerie Gerlach, Linda Gorman, Xiaojia (Sasha) Guo, Tord Hjalt, Ramesh Kekuda, Li Li, John R. MacDougall, Uriel M. Malyankar, Isabelle Millet, Muralidhara Padigaru, Meera Patturajan, Carol E. A. Pena, Luca Rastelli, Richard A. Shimkets, Kimberly A. Spytek, David J. Stone, Corine A.M. Vernet, Edward Z. Voss, Bryan D. Zerhusen.
Application Number | 20060063200 11/051724 |
Document ID | / |
Family ID | 30119581 |
Filed Date | 2006-03-23 |
United States Patent
Application |
20060063200 |
Kind Code |
A1 |
Anderson; David W. ; et
al. |
March 23, 2006 |
Therapeutic polypeptides, nucleic acids encoding same, and methods
of use
Abstract
Disclosed herein are nucleic acid sequences that encode
G-coupled protein-receptor related polypeptides. Also disclosed are
polypeptides encoded by these nucleic acid sequences, and
antibodies, which immunospecifically-bind to the polypeptide, as
well as derivatives, variants, mutants, or fragments of the
aforementioned polypeptide, polynucleotide, or antibody. The
invention further discloses therapeutic, diagnostic and research
methods for diagnosis, treatment, and prevention of disorders
involving any one of these novel human nucleic acids and
proteins.
Inventors: |
Anderson; David W.;
(Branford, CT) ; Baumgartner; Jason C.; (New
Haven, CT) ; Boldog; Ferenc L.; (North Haven, CT)
; Casman; Stacie J.; (North Haven, CT) ; Edinger;
Shlomit R.; (New Haven, CT) ; Gangolli; Esha A.;
(Madison, CT) ; Gerlach; Valerie; (Branford,
CT) ; Gorman; Linda; (Branford, CT) ; Guo;
Xiaojia (Sasha); (Branford, CT) ; Hjalt; Tord;
(East Haven, CT) ; Kekuda; Ramesh; (Norwalk,
CT) ; Li; Li; (Branford, CT) ; MacDougall;
John R.; (Hamden, CT) ; Malyankar; Uriel M.;
(Branford, CT) ; Millet; Isabelle; (Milford,
CT) ; Padigaru; Muralidhara; (Branford, CT) ;
Patturajan; Meera; (Branford, CT) ; Pena; Carol E.
A.; (New Haven, CT) ; Rastelli; Luca;
(Guilford, CT) ; Shimkets; Richard A.; (Guilford,
CT) ; Stone; David J.; (Guilford, CT) ;
Spytek; Kimberly A.; (New Haven, CT) ; Vernet; Corine
A.M.; (Branford, CT) ; Voss; Edward Z.;
(Wallingford, CT) ; Zerhusen; Bryan D.; (Branford,
CT) |
Correspondence
Address: |
CURAGEN CORPORATION
322 EAST MAIN STREET
BRANFORD
CT
06405
US
|
Assignee: |
CuraGen Corporation
555 Long Wharf Drive 11th Floor
New Haven
CT
06511
|
Family ID: |
30119581 |
Appl. No.: |
11/051724 |
Filed: |
February 2, 2005 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10162335 |
Jun 3, 2002 |
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11051724 |
Feb 2, 2005 |
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60295607 |
Jun 4, 2001 |
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60295661 |
Jun 4, 2001 |
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60296404 |
Jun 6, 2001 |
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60296418 |
Jun 6, 2001 |
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60297414 |
Jun 11, 2001 |
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60297567 |
Jun 12, 2001 |
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60298285 |
Jun 14, 2001 |
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60298556 |
Jun 15, 2001 |
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60299949 |
Jun 21, 2001 |
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60300883 |
Jun 26, 2001 |
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60301550 |
Jun 28, 2001 |
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60311972 |
Aug 13, 2001 |
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60315069 |
Aug 27, 2001 |
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60315071 |
Aug 27, 2001 |
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60315660 |
Aug 29, 2001 |
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60322293 |
Sep 14, 2001 |
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60322706 |
Sep 17, 2001 |
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60341186 |
Dec 14, 2001 |
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60361189 |
Feb 28, 2002 |
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60363673 |
Mar 12, 2002 |
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60363676 |
Mar 12, 2002 |
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Current U.S.
Class: |
435/7.1 ;
435/320.1; 435/325; 435/69.1; 530/350; 530/388.15; 536/23.5 |
Current CPC
Class: |
A61K 38/00 20130101;
A61K 39/00 20130101; A61K 48/00 20130101; C07K 14/47 20130101 |
Class at
Publication: |
435/007.1 ;
530/350; 530/388.15; 435/069.1; 435/320.1; 435/325; 536/023.5 |
International
Class: |
G01N 33/53 20060101
G01N033/53; C07H 21/04 20060101 C07H021/04; C12P 21/06 20060101
C12P021/06; C07K 14/705 20060101 C07K014/705; C07K 16/18 20060101
C07K016/18 |
Claims
1. An isolated polypeptide comprising an amino acid sequenced
selected from the group consisting of SEQ ID NO:2n, wherein n is an
integer between 1 and 54
2. An isolated polypeptide comprising a mature form of the amino
acid sequence of claim 1.
3. (canceled)
4. An isolated polypeptide comprising an amino acid sequence having
one or more conservative substitutions in the amino acid sequence
of claim 1.
5. (canceled)
6. A composition comprising the polypeptide of claim 1 and a
carrier.
7.-19. (canceled)
20. An isolated nucleic acid molecule comprising a nucleic acid
sequence encoding the polypeptide of claim 1.
21. (canceled)
22. A nucleic acid molecule, wherein the nucleic acid molecule
differs by a single nucleotide from a nucleic acid sequence of
claim 20.
23. An isolated nucleic acid molecule encoding the polypeptide of
claim 2.
24. (canceled)
25. (canceled)
26. A vector comprising the nucleic acid molecule of claim 20.
27. (canceled)
28. A cell comprising the vector of claim 26.
29. An antibody that immunospecifically binds to the polypeptide of
claim 1.
30. The antibody of claim 29, wherein the antibody is a monoclonal
antibody.
31. The antibody of claim 29, wherein the antibody is a humanized
antibody.
32.-40. (canceled)
41. A method of producing the polypeptide of claim 1, the method
comprising culturing a cell under conditions that lead to
expression of the polypeptide, wherein said cell comprises a vector
comprising an isolated nucleic acid molecule comprising a nucleic
acid sequence selected from the group consisting of SEQ ID NO:2n-1,
wherein n is an integer between 1 and 54.
42.-45. (canceled)
46. An isolated polypeptide comprising an amino acid sequence of
SEQ ID NO: 48.
47. The isolated polypeptide of claim 46 consisting of amino acid
sequence of SEQ ID NO: 48.
48. An isolated polypeptide comprising an amino acid sequence
having one or more conservative substitutions to SEQ ID NO: 48.
49. An isolated polypeptide comprising an amino acid sequence that
is at least 95% identical to the amino acid sequence of SEQ ID NO:
48.
50. A pharmaceutical composition comprising the polypeptide of
claim 46, and a pharmaceutically acceptable carrier.
51. A pharmaceutical composition comprising the polypeptide of
claim 48, and a pharmaceutically acceptable carrier.
52. A pharmaceutical composition comprising the polypeptide of
claim 49, and a pharmaceutically acceptable carrier.
Description
RELATED APPLICATIONS
[0001] This application is a continuation application of U.S.
patent application Ser. No. 10/162,335, filed on Jun. 3, 2002,
which claims priority from Provisional Applications U.S. Ser. No.
60/295,607, filed Jun. 4, 2001; U.S. Ser. No. 60/295,661, filed
Jun. 4, 2001; U.S. Ser. No. 60/296,404, filed Jun. 6, 2001; U.S.
Ser. No. 60/296,418, filed Jun. 6, 2001; U.S. Ser. No. 60/297,414,
filed Jun. 11, 2001; U.S. Ser. No. 60/297,567, filed Jun. 12, 2001;
U.S. Ser. No. 60/298,285, filed Jun. 14, 2001; U.S. Ser. No.
60/298,556, filed Jun. 15, 2001; U.S. Ser. No. 60/299,949, filed
Jun. 21, 2001; U.S. Ser. No. 60/300,883, filed Jun. 26, 2001; U.S.
Ser. No. 60/301,550, filed Jun. 28, 2001; U.S. Ser. No. 60/311,972,
filed Aug. 13, 2001; U.S. Ser. No. 60/315,069, filed Aug. 27, 2001;
U.S. Ser. No. 60/315,071, filed Aug. 27, 2001; U.S. Ser. No.
60/315,660, filed Aug. 29, 2001; U.S. Ser. No. 60/322,293, filed
Sep. 14, 2001; U.S. Ser. No. 60/322,706, filed Sep. 17, 2001; U.S.
Ser. No. 60/341,186, filed Dec. 14, 2001; U.S. Ser. No. 60/361,189,
filed Feb. 28, 2002; U.S. Ser. No. 60/363,673, filed Mar. 12, 2002,
and U.S. Ser. No. 60/363,676, filed Mar. 12, 2002, each of which is
incorporated by reference in its entirety.
FIELD OF THE INVENTION
[0002] The present invention relates to novel polypeptides, and the
nucleic acids encoding them, having properties related to
stimulation of biochemical or physiological responses in a cell, a
tissue, an organ or an organism. More particularly, the novel
polypeptides are gene products of novel genes, or are specified
biologically active fragments or derivatives thereof. Methods of
use encompass diagnostic and prognostic assay procedures as well as
methods of treating diverse pathological conditions.
BACKGROUND OF THE INVENTION
[0003] Eukaryotic cells are characterized by biochemical and
physiological processes, which under normal conditions are
exquisitely balanced to achieve the preservation and propagation of
the cells. When such cells are components of multicellular
organisms such as vertebrates or, more particularly, organisms such
as mammals, the regulation of the biochemical and physiological
processes involves intricate signaling pathways. Frequently, such
signaling pathways include constituted of extracellular signaling
proteins, cellular receptors that bind the signaling proteins and
signal transducing components located within the cells.
[0004] Signaling proteins may be classified as endocrine effectors,
paracrine effectors or autocrine effectors. Endocrine effectors are
signaling molecules secreted by a given organ into the circulatory
system, which are then transported to a distant target organ or
tissue. The target cells include the receptors for the endocrine
effector, and when the endocrine effector binds, a signaling
cascade is induced. Paracrine effectors involve secreting cells and
receptor cells in close proximity to each other, such as two
different classes of cells in the same tissue or organ. One class
of cells secretes the paracrine effector, which then reaches the
second class of cells, for example by diffusion through the
extracellular fluid. The second class of cells contains the
receptors for the paracrine effector; binding of the effector
results in induction of the signaling cascade that elicits the
corresponding biochemical or physiological effect. Autocrine
effectors are highly analogous to paracrine effectors, except that
the same cell type that secretes the autocrine effector also
contains the receptor. Thus the autocrine effector binds to
receptors on the same cell, or on identical neighboring cells. The
binding process then elicits the characteristic biochemical or
physiological effect.
[0005] Signaling processes may elicit a variety of effects on cells
and tissues including, by way of nonlimiting example, induction of
cell or tissue proliferation, suppression of growth or
proliferation, induction of differentiation or maturation of a cell
or tissue, and suppression of differentiation or maturation of a
cell or tissue.
[0006] Many pathological conditions involve dysregulation of
expression of important effector proteins. In certain classes of
pathologies the dysregulation is manifested as diminished or
suppressed level of synthesis and secretion of protein effectors.
In other classes of pathologies the dysregulation is manifested as
increased or up-regulated level of synthesis and secretion of
protein effectors. In a clinical setting a subject may be suspected
of suffering from a condition brought on by altered or
mis-regulated levels of a protein effector of interest. Therefore
there is a need to assay for the level of the protein effector of
interest in a biological sample from such a subject, and to compare
the level with that characteristic of a nonpathological condition.
There also is a need to provide the protein effector as a product
of manufacture. Administration of the effector to a subject in need
thereof is useful in treatment of the pathological condition.
Accordingly, there is a need for a method of treatment of a
pathological condition brought on by a diminished or suppressed
levels of the protein effector of interest. In addition, there is a
need for a method of treatment of a pathological condition brought
on by a increased or up-regulated levels of the protein effector of
interest.
SUMMARY OF THE INVENTION
[0007] The invention is based in part upon the discovery of
isolated polypeptides including amino acid sequences selected from
mature forms of the amino acid sequences selected from the group
consisting of SEQ ID NO:2n, wherein n is an integer between 1 and
54. The invention also is based in part upon variants of a mature
form of the amino acid sequence selected from the group consisting
of SEQ ID NO:2n, wherein n is an integer between 1 and 54, wherein
any amino acid in the mature form is changed to a different amino
acid, provided that no more than 15% of the amino acid residues in
the sequence of the mature form are so changed. In another
embodiment, the invention includes the amino acid sequences
selected from the group consisting of SEQ ID NO:2n, wherein n is an
integer between 1 and 54. In another embodiment, the invention also
comprises variants of the amino acid sequence selected from the
group consisting of SEQ ID NO:2n, wherein n is an integer between 1
and 54 wherein any amino acid specified in the chosen sequence is
changed to a different amino acid, provided that no more than 15%
of the amino acid residues in the sequence are so changed. The
invention also involves fragments of any of the mature forms of the
amino acid sequences selected from the group consisting of SEQ ID
NO:2n, wherein n is an integer between 1 and 54, or any other amino
acid sequence selected from this group. The invention also
comprises fragments from these groups in which up to 15% of the
residues are changed.
[0008] In another embodiment, the invention encompasses
polypeptides that are naturally occurring allelic variants of the
sequence selected from the group consisting of SEQ ID NO:2n,
wherein n is an integer between 1 and 54. These allelic variants
include amino acid sequences that are the translations of nucleic
acid sequences differing by a single nucleotide from nucleic acid
sequences selected from the group consisting of SEQ ID NOS: 2n-1,
wherein n is an integer between 1 and 54. The variant polypeptide
where any amino acid changed in the chosen sequence is changed to
provide a conservative substitution.
[0009] In another embodiment, the invention comprises a
pharmaceutical composition involving a polypeptide with an amino
acid sequence selected from the group consisting of SEQ ID NO:2n,
wherein n is an integer between 1 and 54 and a pharmaceutically
acceptable carrier. In another embodiment, the invention involves a
kit, including, in one or more containers, this pharmaceutical
composition.
[0010] In another embodiment, the invention includes the use of a
therapeutic in the manufacture of a medicament for treating a
syndrome associated with a human disease, the disease being
selected from a pathology associated with a polypeptide with an
amino acid sequence selected from the group consisting of SEQ ID
NO:2n, wherein n is an integer between 1 and 54 wherein said
therapeutic is the polypeptide selected from this group.
[0011] In another embodiment, the invention comprises a method for
determining the presence or amount of a polypeptide with an amino
acid sequence selected from the group consisting of SEQ ID NO:2n,
wherein n is an integer between 1 and 54 in a sample, the method
involving providing the sample; introducing the sample to an
antibody that binds immunospecifically to the polypeptide; and
determining the presence or amount of antibody bound to the
polypeptide, thereby determining the presence or amount of
polypeptide in the sample.
[0012] In another embodiment, the invention includes a method for
determining the presence of or predisposition to a disease
associated with altered levels of a polypeptide with an amino acid
sequence selected from the group consisting of SEQ ID NO:2n,
wherein n is an integer between 1 and 54 in a first mammalian
subject, the method involving measuring the level of expression of
the polypeptide in a sample from the first mammalian subject; and
comparing the amount of the polypeptide in this sample to the
amount of the polypeptide present in a control sample from a second
mammalian subject known not to have, or not to be predisposed to,
the disease, wherein an alteration in the expression level of the
polypeptide in the first subject as compared to the control sample
indicates the presence of or predisposition to the disease.
[0013] In another embodiment, the invention involves a method of
identifying an agent that binds to a polypeptide with an amino acid
sequence selected from the group consisting of SEQ ID NO:2n,
wherein n is an integer between 1 and 54, the method including
introducing the polypeptide to the agent; and determining whether
the agent binds to the polypeptide. The agent could be a cellular
receptor or a downstream effector.
[0014] In another embodiment, the invention involves a method for
identifying a potential therapeutic agent for use in treatment of a
pathology, wherein the pathology is related to aberrant expression
or aberrant physiological interactions of a polypeptide with an
amino acid sequence selected from the group consisting of SEQ ID
NO:2n, wherein n is an integer between 1 and 54, the method
including providing a cell expressing the polypeptide of the
invention and having a property or function ascribable to the
polypeptide; contacting the cell with a composition comprising a
candidate substance; and determining whether the substance alters
the property or function ascribable to the polypeptide; whereby, if
an alteration observed in the presence of the substance is not
observed when the cell is contacted with a composition devoid of
the substance, the substance is identified as a potential
therapeutic agent.
[0015] In another embodiment, the invention involves a method for
screening for a modulator of activity or of latency or
predisposition to a pathology associated with a polypeptide having
an amino acid sequence selected from the group consisting of SEQ ID
NO:2n, wherein n is an integer between 1 and 54, the method
including administering a test compound to a test animal at
increased risk for a pathology associated with the polypeptide of
the invention, wherein the test animal recombinantly expresses the
polypeptide of the invention; measuring the activity of the
polypeptide in the test animal after administering the test
compound; and comparing the activity of the protein in the test
animal with the activity of the polypeptide in a control animal not
administered the polypeptide, wherein a change in the activity of
the polypeptide in the test animal relative to the control animal
indicates the test compound is a modulator of latency of, or
predisposition to, a pathology associated with the polypeptide of
the invention. The recombinant test animal could express a test
protein transgene or express the transgene under the control of a
promoter at an increased level relative to a wild-type test animal
The promoter may or may not b the native gene promoter of the
transgene.
[0016] In another embodiment, the invention involves a method for
modulating the activity of a polypeptide with an amino acid
sequence selected from the group consisting of SEQ ID NO:2n,
wherein n is an integer between 1 and 54, the method including
introducing a cell sample expressing the polypeptide with a
compound that binds to the polypeptide in an amount sufficient to
modulate the activity of the polypeptide.
[0017] In another embodiment, the invention involves a method of
treating or preventing a pathology associated with a polypeptide
with an amino acid sequence selected from the group consisting of
SEQ ID NO:2n, wherein n is an integer between 1 and 54, the method
including administering the polypeptide to a subject in which such
treatment or prevention is desired in an amount sufficient to treat
or prevent the pathology in the subject. The subject could be
human.
[0018] In another embodiment, the invention involves a method of
treating a pathological state in a mammal, the method including
administering to the mammal a polypeptide in an amount that is
sufficient to alleviate the pathological state, wherein the
polypeptide is a polypeptide having an amino acid sequence at least
95% identical to a polypeptide having the amino acid sequence
selected from the group consisting of SEQ ID NO:2n, wherein n is an
integer between 1 and 54 or a biologically active fragment
thereof.
[0019] In another embodiment, the invention involves an isolated
nucleic acid molecule comprising a nucleic acid sequence encoding a
polypeptide having an amino acid sequence selected from the group
consisting of a mature form of the amino acid sequence given SEQ ID
NO:2n, wherein n is an integer between 1 and 54; a variant of a
mature form of the amino acid sequence selected from the group
consisting of SEQ ID NO:2n, wherein n is an integer between 1 and
54 wherein any amino acid in the mature form of the chosen sequence
is changed to a different amino acid, provided that no more than
15% of the amino acid residues in the sequence of the mature form
are so changed; the amino acid sequence selected from the group
consisting of SEQ ID NO:2n, wherein n is an integer between 1 and
54; a variant of the amino acid sequence selected from the group
consisting of SEQ ID NO:2n, wherein n is an integer between 1 and
54, in which any amino acid specified in the chosen sequence is
changed to a different amino acid, provided that no more than 15%
of the amino acid residues in the sequence are so changed; a
nucleic acid fragment encoding at least a portion of a polypeptide
comprising the amino acid sequence selected from the group
consisting of SEQ ID NO:2n, wherein n is an integer between 1 and
54 or any variant of the polypeptide wherein any amino acid of the
chosen sequence is changed to a different amino acid, provided that
no more than 10% of the amino acid residues in the sequence are so
changed; and the complement of any of the nucleic acid
molecules.
[0020] In another embodiment, the invention comprises an isolated
nucleic acid molecule having a nucleic acid sequence encoding a
polypeptide comprising an amino acid sequence selected from the
group consisting of a mature form of the amino acid sequence given
SEQ ID NO:2n, wherein n is an integer between 1 and 54, wherein the
nucleic acid molecule comprises the nucleotide sequence of a
naturally occurring allelic nucleic acid variant.
[0021] In another embodiment, the invention involves an isolated
nucleic acid molecule including a nucleic acid sequence encoding a
polypeptide having an amino acid sequence selected from the group
consisting of a mature form of the amino acid sequence given SEQ ID
NO:2n, wherein n is an integer between 1 and 54 that encodes a
variant polypeptide, wherein the variant polypeptide has the
polypeptide sequence of a naturally occurring polypeptide
variant.
[0022] In another embodiment, the invention comprises an isolated
nucleic acid molecule having a nucleic acid sequence encoding a
polypeptide comprising an amino acid sequence selected from the
group consisting of a mature form of the amino acid sequence given
SEQ ID NO:2n, wherein n is an integer between 1 and 54, wherein the
nucleic acid molecule differs by a single nucleotide from a nucleic
acid sequence selected from the group consisting of SEQ ID NOS:
2n-1, wherein n is an integer between 1 and 54.
[0023] In another embodiment, the invention includes an isolated
nucleic acid molecule having a nucleic acid sequence encoding a
polypeptide including an amino acid sequence selected from the
group consisting of a mature form of the amino acid sequence given
SEQ ID NO:2n, wherein n is an integer between 1 and 54, wherein the
nucleic acid molecule comprises a nucleotide sequence selected from
the group consisting of the nucleotide sequence selected from the
group consisting of SEQ ID NO:2n-1, wherein n is an integer between
1 and 54; a nucleotide sequence wherein one or more nucleotides in
the nucleotide sequence selected from the group consisting of SEQ
ID NO:2n-1, wherein n is an integer between 1 and 54 is changed
from that selected from the group consisting of the chosen sequence
to a different nucleotide provided that no more than 15% of the
nucleotides are so changed; a nucleic acid fragment of the sequence
selected from the group consisting of SEQ ID NO:2n-1, wherein n is
an integer between 1 and 54; and a nucleic acid fragment wherein
one or more nucleotides in the nucleotide sequence selected from
the group consisting of SEQ ID NO:2n-1, wherein n is an integer
between 1 and 54 is changed from that selected from the group
consisting of the chosen sequence to a different nucleotide
provided that no more than 15% of the nucleotides are so
changed.
[0024] In another embodiment, the invention includes an isolated
nucleic acid molecule having a nucleic acid sequence encoding a
polypeptide including an amino acid sequence selected from the
group consisting of a mature form of the amino acid sequence given
SEQ ID NO:2n, wherein n is an integer between 1 and 54, wherein the
nucleic acid molecule hybridizes under stringent conditions to the
nucleotide sequence selected from the group consisting of SEQ ID
NO:2n-1, wherein n is an integer between 1 and 54, or a complement
of the nucleotide sequence.
[0025] In another embodiment, the invention includes an isolated
nucleic acid molecule having a nucleic acid sequence encoding a
polypeptide including an amino acid sequence selected from the
group consisting of a mature form of the amino acid sequence given
SEQ ID NO:2n, wherein n is an integer between 1 and 54, wherein the
nucleic acid molecule has a nucleotide sequence in which any
nucleotide specified in the coding sequence of the chosen
nucleotide sequence is changed from that selected from the group
consisting of the chosen sequence to a different nucleotide
provided that no more than 15% of the nucleotides in the chosen
coding sequence are so changed, an isolated second polynucleotide
that is a complement of the first polynucleotide, or a fragment of
any of them.
[0026] In another embodiment, the invention includes a vector
involving the nucleic acid molecule having a nucleic acid sequence
encoding a polypeptide including an amino acid sequence selected
from the group consisting of a mature form of the amino acid
sequence given SEQ ID NO:2n, wherein n is an integer between 1 and
54. This vector can have a promoter operably linked to the nucleic
acid molecule. This vector can be located within a cell.
[0027] In another embodiment, the invention involves a method for
determining the presence or amount of a nucleic acid molecule
having a nucleic acid sequence encoding a polypeptide including an
amino acid sequence selected from the group consisting of a mature
form of the amino acid sequence given SEQ ID NO:2n, wherein n is an
integer between 1 and 54 in a sample, the method including
providing the sample; introducing the sample to a probe that binds
to the nucleic acid molecule; and determining the presence or
amount of the probe bound to the nucleic acid molecule, thereby
determining the presence or amount of the nucleic acid molecule in
the sample. The presence or amount of the nucleic acid molecule is
used as a marker for cell or tissue type. The cell type can be
cancerous.
[0028] In another embodiment, the invention involves a method for
determining the presence of or predisposition for a disease
associated with altered levels of a nucleic acid molecule having a
nucleic acid sequence encoding a polypeptide including an amino
acid sequence selected from the group consisting of a mature form
of the amino acid sequence given SEQ ID NO:2n, wherein n is an
integer between 1 and 54 in a first mammalian subject, the method
including measuring the amount of the nucleic acid in a sample from
the first mammalian subject; and comparing the amount of the
nucleic acid in the sample of step (a) to the amount of the nucleic
acid present in a control sample from a second mammalian subject
known not to have or not be predisposed to, the disease; wherein an
alteration in the level of the nucleic acid in the first subject as
compared to the control sample indicates the presence of or
predisposition to the disease.
[0029] Unless otherwise defined, all technical and scientific terms
used herein have the same meaning as commonly understood by one of
ordinary skill in the art to which this invention belongs. Although
methods and materials similar or equivalent to those described
herein can be used in the practice or testing of the present
invention, suitable methods and materials are described below. All
publications, patent applications, patents, and other references
mentioned herein are incorporated by reference in their entirety.
In the case of conflict, the present specification, including
definitions, will control. In addition, the materials, methods, and
examples are illustrative only and not intended to be limiting.
[0030] Other features and advantages of the invention will be
apparent from the following detailed description and claims.
DETAILED DESCRIPTION OF THE INVENTION
[0031] The present invention provides novel nucleotides and
polypeptides encoded thereby. Included in the invention are the
novel nucleic acid sequences, their encoded polypeptides,
antibodies, and other related compounds. The sequences are
collectively referred to herein as "NOVX nucleic acids" or "NOVX
polynucleotides" and the corresponding encoded polypeptides are
referred to as "NOVX polypeptides" or "NOVX proteins." Unless
indicated otherwise, "NOVX" is meant to refer to any of the novel
sequences disclosed herein. Table 1 provides a summary of the NOVX
nucleic acids and their encoded polypeptides. TABLE-US-00001 TABLE
1 Sequences and Corresponding SEQ ID Numbers SEQ ID SEQ ID NO NO
NOVX Internal (nucleic (amino Assignment Identification acid) acid)
Homology Nov1a CG100488-01 1 2 Elastase 2B like homo sapiens Nov1b
CG100488-06 3 4 Elastase 2B like homo sapiens Nov1c CG100488-07 5 6
Elastase 2B like homo sapiens Nov1d CG100488-08 7 8 Elastase 2B
like homo sapiens Nov1e CG100488-09 9 10 Elastase 2B like homo
sapiens Nov1f 198353297 11 12 Elastase 2B like homo sapiens Nov1g
198353301 13 14 Elastase 2B like homo sapiens Nov1h 198353319 15 16
Elastase 2B like homo sapiens Nov1i 198362547 17 18 Elastase 2B
like homo sapiens Nov1j 198362642 19 20 Elastase 2B like homo
sapiens Nov2a CG100560-01 21 22 Leucine Rich Repeat like homo
sapiens Nov2b CG100560-02 23 24 Leucine Rich Repeat like homo
sapiens Nov3a CG101012-01 25 26 Gonadotrophin beta-subunit like
homo sapiens Nov4a CG101584-01 27 28 odorant binding protein like
homo sapiens Nov5a CG101707-01 29 30 Complement C1q Nov6a
CG101836-01 31 32 Cathepsin F like homo sapiens Nov6b CG101836-02
33 34 Cathepsin F like homo sapiens Nov7a CG102221-01 35 36 netrin
G1 like homo sapiens Nov8a CG102325-01 37 38 Secreted reprolysin
Nov9a CG102832-01 39 40 CAC37763 like homo sapiens Nov9b
CG102832-02 41 42 Ig domain-containing transmembrane protein like
homo sapiens Nov9c 197195425 43 44 Ig domain-containing
transmembrane protein like homo sapiens Nov9d 197192431 45 46 Ig
domain-containing transmembrane protein like homo sapiens Nov9e
197192437 47 48 Ig domain-containing transmembrane protein like
homo sapiens Nov9f 197192443 49 50 Ig domain-containing
transmembrane protein like homo sapiens Nov9g 197192448 51 52 Ig
domain-containing transmembrane protein like homo sapiens Nov10a
CG102942-01 53 54 lipocalin 2 like homo sapiens Nov10b CG102942-03
55 56 Neutrophil Gelatinase- Associated lipocalin like homo sapiens
Nov10c 237376776 57 58 Neutrophil Gelatinase- Associated lipocalin
like homo sapiens Nov11a CG104016-01 59 60 DENN domain containing
protein like homo sapiens Nov11b 197208336 61 62 DENN domain
containing protein like homo sapiens Nov11c 197306179 63 64 DENN
domain containing protein like homo sapiens Nov11d 219903686 65 66
DENN domain containing protein like homo sapiens Nov11e 219903690
67 68 DENN domain containing protein like homo sapiens Nov12a
CG104903-01 69 70 Kininogen Precursor like homo sapiens Nov12b
CG104903-02 71 73 Kininogen Precursor like homo sapiens Nov12c
CG104903-03 73 74 Kininogen Precursor like homo sapiens Nov12d
CG104903-05 75 76 Kininogen Precursor like homo sapiens Nov12e
CG104903-06 77 78 Kininogen Precursor like homo sapiens Nov12f
CG104903-07 79 80 Kininogen Precursor like homo sapiens Nov12g
CG104903-08 81 82 Kininogen Precursor like homo sapiens Nov12h
CG104903-09 83 84 Kininogen Precursor like homo sapiens Nov13a
CG105982-01 85 86 Serine Protease-CUB Domain Protein like homo
sapiens Nov14a CG107614-02 87 88 Hemopexin-like Nov15a CG109445-01
89 90 neuronal leucine-rich repeat protein like homo sapiens Nov16a
CG109496-01 91 92 neuronal leucine-rich repeat protein like homo
sapiens Nov17a CG109532-01 93 94 Immunoglobulin domains containing
protein like homo sapiens Nov17b 207775340 95 96 Immunoglobulin
domains containing protein like homo sapiens Nov17c 207775361 97 98
Immunoglobulin domains containing protein like homo sapiens Nov17d
207775365 99 100 Immunoglobulin domains containing protein like
homo sapiens Nov18a CG50213-01 101 102 small inducible cytokine
subfamily B member 14 (BRAK) Nov18b CG50213-02 103 104 small
inducible cytokine subfamily B member 14 (BRAK) Nov18c CG50213-03
105 106 small inducible cytokine subfamily B member 14 (BRAK)
Nov19a CG88912-02 107 108 BETA-NEOENDORPHIN- DYNORPHIN PRECURSOR
like homo sapiens
[0032] Table 1 indicates homology of NOVX nucleic acids to known
protein families. Thus, the nucleic acids and polypeptides,
antibodies and related compounds according to the invention
corresponding to a NOVX as identified in column 1 of Table 1 will
be useful in therapeutic and diagnostic applications implicated in,
for example, pathologies and disorders associated with the known
protein families identified in column 5 of Table 1.
[0033] NOVX nucleic acids and their encoded polypeptides are useful
in a variety of applications and contexts. The various NOVX nucleic
acids and polypeptides according to the invention are useful as
novel members of the protein families according to the presence of
domains and sequence relatedness to previously described proteins.
Additionally, NOVX nucleic acids and polypeptides can also be used
to identify proteins that are members of the family to which the
NOVX polypeptides belong.
[0034] Consistent with other known members of the family of
proteins, identified in column 5 of Table 1, the NOVX polypeptides
of the present invention show homology to, and contain domains that
are characteristic of, other members of such protein families.
Details of the sequence relatedness and domain analysis for each
NOVX are presented in Example A.
[0035] The NOVX nucleic acids and polypeptides can also be used to
screen for molecules, which inhibit or enhance NOVX activity or
function. Specifically, the nucleic acids and polypeptides
according to the invention may be used as targets for the
identification of small molecules that modulate or inhibit diseases
associated with the protein families listed in Table 1.
[0036] The NOVX nucleic acids and polypeptides are also useful for
detecting specific cell types. Details of the expression analysis
for each NOVX are presented in Example C. Accordingly, the NOVX
nucleic acids, polypeptides, antibodies and related compounds
according to the invention will have diagnostic and therapeutic
applications in the detection of a variety of diseases with
differential expression in normal vs. diseased tissues, e.g. a
variety of cancers.
[0037] Additional utilities for NOVX nucleic acids and polypeptides
according to the invention are disclosed herein.
[0038] NOVX Clones
[0039] NOVX nucleic acids and their encoded polypeptides are useful
in a variety of applications and contexts. The various NOVX nucleic
acids and polypeptides according to the invention are useful as
novel members of the protein families according to the presence of
domains and sequence relatedness to previously described proteins.
Additionally, NOVX nucleic acids and polypeptides can also be used
to identify proteins that are members of the family to which the
NOVX polypeptides belong.
[0040] The NOVX genes and their corresponding encoded proteins are
useful for preventing, treating or ameliorating medical conditions,
e.g., by protein or gene therapy. Pathological conditions can be
diagnosed by determining the amount of the new protein in a sample
or by determining the presence of mutations in the new genes.
Specific uses are described for each of the NOVX genes, based on
the tissues in which they are most highly expressed. Uses include
developing products for the diagnosis or treatment of a variety of
diseases and disorders.
[0041] The NOVX nucleic acids and proteins of the invention are
useful in potential diagnostic and therapeutic applications and as
a research tool. These include serving as a specific or selective
nucleic acid or protein diagnostic and/or prognostic marker,
wherein the presence or amount of the nucleic acid or the protein
are to be assessed, as well as potential therapeutic applications
such as the following: (i) a protein therapeutic, (ii) a small
molecule drug target, (iii) an antibody target (therapeutic,
diagnostic, drug targeting/cytotoxic antibody), (iv) a nucleic acid
useful in gene therapy (gene delivery/gene ablation), and (v) a
composition promoting tissue regeneration in vitro and in vivo (vi)
biological defense weapon.
[0042] In one specific embodiment, the invention includes an
isolated polypeptide comprising an amino acid sequence selected
from the group consisting of: (a) a mature form of the amino acid
sequence selected from the group consisting of SEQ ID NO:2n,
wherein n is an integer between 1 and 54; (b) a variant of a mature
form of the amino acid sequence selected from the group consisting
of SEQ ID NO:2n, wherein n is an integer between 1 and 54, wherein
any amino acid in the mature form is changed to a different amino
acid, provided that no more than 15% of the amino acid residues in
the sequence of the mature form are so changed; (c) an amino acid
sequence selected from the group consisting of SEQ ID NO:2n,
wherein n is an integer between 1 and 54; (d) a variant of the
amino acid sequence selected from the group consisting of SEQ ID
NO:2n, wherein n is an integer between 1 and 54 wherein any amino
acid specified in the chosen sequence is changed to a different
amino acid, provided that no more than 15% of the amino acid
residues in the sequence are so changed; and (e) a fragment of any
of (a) through (d).
[0043] In another specific embodiment, the invention includes an
isolated nucleic acid molecule comprising a nucleic acid sequence
encoding a polypeptide comprising an amino acid sequence selected
from the group consisting of: (a) a mature form of the amino acid
sequence given SEQ ID NO:2n, wherein n is an integer between 1 and
54; (b) a variant of a mature form of the amino acid sequence
selected from the group consisting of SEQ ID NO:2n, wherein n is an
integer between 1 and 54 wherein any amino acid in the mature form
of the chosen sequence is changed to a different amino acid,
provided that no more than 15% of the amino acid residues in the
sequence of the mature form are so changed; (c) the amino acid
sequence selected from the group consisting of SEQ ID NO:2n,
wherein n is an integer between 1 and 54; (d) a variant of the
amino acid sequence selected from the group consisting of SEQ ID
NO:2n, wherein n is an integer between 1 and 54, in which any amino
acid specified in the chosen sequence is changed to a different
amino acid, provided that no more than 15% of the amino acid
residues in the sequence are so changed; (e) a nucleic acid
fragment encoding at least a portion of a polypeptide comprising
the amino acid sequence selected from the group consisting of SEQ
ID NO:2n, wherein n is an integer between 1 and 54 or any variant
of said polypeptide wherein any amino acid of the chosen sequence
is changed to a different amino acid, provided that no more than
10% of the amino acid residues in the sequence are so changed; and
(f) the complement of any of said nucleic acid molecules.
[0044] In yet another specific embodiment, the invention includes
an isolated nucleic acid molecule, wherein said nucleic acid
molecule comprises a nucleotide sequence selected from the group
consisting of: (a) the nucleotide sequence selected from the group
consisting of SEQ ID NO:2n-1, wherein n is an integer between 1 and
54; (b) a nucleotide sequence wherein one or more nucleotides in
the nucleotide sequence selected from the group consisting of SEQ
ID NO:2n-1, wherein n is an integer between 1 and 54 is changed
from that selected from the group consisting of the chosen sequence
to a different nucleotide provided that no more than 15% of the
nucleotides are so changed; (c) a nucleic acid fragment of the
sequence selected from the group consisting of SEQ ID NO:2n-1,
wherein n is an integer between 1 and 54; and (d) a nucleic acid
fragment wherein one or more nucleotides in the nucleotide sequence
selected from the group consisting of SEQ ID NO:2n-1, wherein n is
an integer between 1 and 54 is changed from that selected from the
group consisting of the chosen sequence to a different nucleotide
provided that no more than 15% of the nucleotides are so
changed.
[0045] NOVX Nucleic Acids and Polypeptides
[0046] One aspect of the invention pertains to isolated nucleic
acid molecules that encode NOVX polypeptides or biologically active
portions thereof. Also included in the invention are nucleic acid
fragments sufficient for use as hybridization probes to identify
NOVX-encoding nucleic acids (e.g., NOVX mRNAs) and fragments for
use as PCR primers for the amplification and/or mutation of NOVX
nucleic acid molecules. As used herein, the term "nucleic acid
molecule" is intended to include DNA molecules (e.g., cDNA or
genomic DNA), RNA molecules (e.g., mRNA), analogs of the DNA or RNA
generated using nucleotide analogs, and derivatives, fragments and
homologs thereof. The nucleic acid molecule may be single-stranded
or double-stranded, but preferably is comprised double-stranded
DNA.
[0047] A NOVX nucleic acid can encode a mature NOVX polypeptide. As
used herein, a "mature" form of a polypeptide or protein disclosed
in the present invention is the product of a naturally occurring
polypeptide, precursor form, or proprotein. The naturally occurring
polypeptide, precursor or proprotein includes, by way of
nonlimiting example, the full-length gene product encoded by the
corresponding gene. Alternatively, it may be defined as the
polypeptide, precursor or proprotein encoded by an ORF described
herein. The product "mature" form arises, by way of nonlimiting
example, as a result of one or more naturally occurring processing
steps that may take place within the cell (host cell) in which the
gene product arises. Examples of such processing steps leading to a
"mature" form of a polypeptide or protein include the cleavage of
the N-terminal methionine residue encoded by the initiation codon
of an ORF or the proteolytic cleavage of a signal peptide or leader
sequence. Thus a mature form arising from a precursor polypeptide
or protein that has residues 1 to N, where residue 1 is the
N-terminal methionine, would have residues 2 through N remaining
after removal of the N-terminal methionine. Alternatively, a mature
form arising from a precursor polypeptide or protein having
residues 1 to N, in which an N-terminal signal sequence from
residue 1 to residue M is cleaved, would have the residues from
residue M+1 to residue N remaining. Further as used herein, a
"mature" form of a polypeptide or protein may arise from a
post-translational modification other than a proteolytic cleavage
event. Such additional processes include, by way of non-limiting
example, glycosylation, myristoylation or phosphorylation. In
general, a mature polypeptide or protein may result from the
operation of only one of these processes, or a combination of any
of them.
[0048] The term "probe", as utilized herein, refers to nucleic acid
sequences of variable length, preferably between at least about 10
nucleotides (nt), and 100 nt, or as many as approximately, e.g.,
6,000 nt, depending upon the specific use. Probes are used in the
detection of identical, similar, or complementary nucleic acid
sequences. Longer length probes are generally obtained from a
natural or recombinant source, are highly specific, and much slower
to hybridize than shorter-length oligomer probes. Probes may be
single- or double-stranded and designed to have specificity in PCR,
membrane-based hybridization technologies, or ELISA-like
technologies.
[0049] The term "isolated" nucleic acid molecule, as used herein,
is a nucleic acid which is separated from other nucleic acid
molecules which are present in the natural source of the nucleic
acid. Preferably, an "isolated" nucleic acid is free of sequences
which naturally flank the nucleic acid (i.e., sequences located at
the 5'- and 3'-termini of the nucleic acid) in the genomic DNA of
the organism from which the nucleic acid is derived. For example,
in various embodiments, the isolated NOVX nucleic acid molecules
can contain less than about 5 kb, 4 kb, 3 kb, 2 kb, 1 kb, 0.5 kb,
0.1 kb, or less of nucleotide sequences which naturally flank the
nucleic acid molecule in genomic DNA of the cell/tissue from which
the nucleic acid is derived (e.g., brain, heart, liver, spleen,
etc.). Moreover, an "isolated" nucleic acid molecule, such as a
cDNA molecule, can be substantially free of other cellular
material, culture medium, or of chemical precursors or other
chemicals.
[0050] A nucleic acid molecule of the invention, e.g., a nucleic
acid molecule having the nucleotide sequence SEQ ID NOS: 2n-1,
wherein n is an integer between 1 and 54, or a complement of this
nucleotide sequence, can be isolated using standard molecular
biology techniques and the sequence information provided herein.
Using all or a portion of the nucleic acid sequence of SEQ ID
NOS:2n-1, wherein n is an integer between 1 and 54, as a
hybridization probe, NOVX molecules can be isolated using standard
hybridization and cloning techniques (e.g., as described in
Sambrook, et al., (eds.), MOLECULAR CLONING: A LABORATORY MANUAL
2.sup.nd Ed., Cold Spring Harbor Laboratory Press, Cold Spring
Harbor, N.Y., 1989; and Ausubel, et al., (eds.), CURRENT PROTOCOLS
IN MOLECULAR BIOLOGY, John Wiley & Sons, New York, N.Y.,
1993).
[0051] A nucleic acid of the invention can be amplified using cDNA,
mRNA or, alternatively, genomic DNA as a template with appropriate
oligonucleotide primers according to standard PCR amplification
techniques. The nucleic acid so amplified can be cloned into an
appropriate vector and characterized by DNA sequence analysis.
Furthermore, oligonucleotides corresponding to NOVX nucleotide
sequences can be prepared by standard synthetic techniques, e.g.,
using an automated DNA synthesizer.
[0052] As used herein, the term "oligonucleotide" refers to a
series of linked nucleotide residues. A short oligonucleotide
sequence may be based on, or designed from, a genomic or cDNA
sequence and is used to amplify, confirm, or reveal the presence of
an identical, similar or complementary DNA or RNA in a particular
cell or tissue. Oligonucleotides comprise a nucleic acid sequence
having about 10 nt, 50 nt, or 100 nt in length, preferably about 15
nt to 30 nt in length. In one embodiment of the invention, an
oligonucleotide comprising a nucleic acid molecule less than 100 nt
in length would further comprise at least 6 contiguous nucleotides
of SEQ ID NOS:2n-1, wherein n is an integer between 1 and 54, or a
complement thereof. Oligonucleotides may be chemically synthesized
and may also be used as probes.
[0053] In another embodiment, an isolated nucleic acid molecule of
the invention comprises a nucleic acid molecule that is a
complement of the nucleotide sequence shown in SEQ ID NOS:2n-1,
wherein n is an integer between 1 and 54, or a portion of this
nucleotide sequence (e.g., a fragment that can be used as a probe
or primer or a fragment encoding a biologically-active portion of A
NOVX polypeptide). A nucleic acid molecule that is complementary to
the nucleotide sequence shown SEQ ID NOS:2n-1, wherein n is an
integer between 1 and 54, is one that is sufficiently complementary
to the nucleotide sequence shown SEQ ID NOS:2n-1, wherein n is an
integer between 1 and 54, that it can hydrogen bond with few or no
mismatches to the nucleotide sequence shown SEQ ID NOS:2n-1,
wherein n is an integer between 1 and 54, thereby forming a stable
duplex.
[0054] As used herein, the term "complementary" refers to
Watson-Crick or Hoogsteen base pairing between nucleotides units of
a nucleic acid molecule, and the term "binding" means the physical
or chemical interaction between two polypeptides or compounds or
associated polypeptides or compounds or combinations thereof.
Binding includes ionic, non-ionic, van der Waals, hydrophobic
interactions, and the like. A physical interaction can be either
direct or indirect. Indirect interactions may be through or due to
the effects of another polypeptide or compound. Direct binding
refers to interactions that do not take place through, or due to,
the effect of another polypeptide or compound, but instead are
without other substantial chemical intermediates.
[0055] "Fragments" provided herein are defined as sequences of at
least 6 (contiguous) nucleic acids or at least 4 (contiguous) amino
acids, a length sufficient to allow for specific hybridization in
the case of nucleic acids or for specific recognition of an epitope
in the case of amino acids, and are at most some portion less than
a full length sequence. Fragments may be derived from any
contiguous portion of a nucleic acid or amino acid sequence of
choice.
[0056] A full-length NOVX clone is identified as containing an ATG
translation start codon and an in-frame stop codon. Any disclosed
NOVX nucleotide sequence lacking an ATG start codon therefore
encodes a truncated C-terminal fragment of the respective NOVX
polypeptide, and requires that the corresponding full-length cDNA
extend in the 5' direction of the disclosed sequence. Any disclosed
NOVX nucleotide sequence lacking an in-frame stop codon similarly
encodes a truncated N-terminal fragment of the respective NOVX
polypeptide, and requires that the corresponding full-length cDNA
extend in the 3' direction of the disclosed sequence.
[0057] "Derivatives" are nucleic acid sequences or amino acid
sequences formed from the native compounds either directly, by
modification, or by partial substitution. "Analogs" are nucleic
acid sequences or amino acid sequences that have a structure
similar to, but not identical to, the native compound, e.g. they
differ from it in respect to certain components or side chains.
Analogs may be synthetic or derived from a different evolutionary
origin and may have a similar or opposite metabolic activity
compared to wild type. Homologs are nucleic acid sequences or amino
acid sequences of a particular gene that are derived from different
species.
[0058] Derivatives and analogs may be full length or other than
full length. Derivatives or analogs of the nucleic acids or
proteins of the invention include, but are not limited to,
molecules comprising regions that are substantially homologous to
the nucleic acids or proteins of the invention, in various
embodiments, by at least about 70%, 80%, or 95% identity (with a
preferred identity of 80-95%) over a nucleic acid or amino acid
sequence of identical size or when compared to an aligned sequence
in which the alignment is done by a computer homology program known
in the art, or whose encoding nucleic acid is capable of
hybridizing to the complement of a sequence encoding the proteins
of the invention under stringent, moderately stringent, or low
stringent conditions. See e.g. Ausubel, et al., CURRENT PROTOCOLS
IN MOLECULAR BIOLOGY, John Wiley & Sons, New York, N.Y., 1993,
and below.
[0059] A "homologous nucleic acid sequence" or "homologous amino
acid sequence," or variations thereof, refer to sequences
characterized by a homology at the nucleotide level or amino acid
level as discussed above. Homologous nucleotide sequences include
those sequences coding for isoforms of NOVX polypeptides. Isoforms
can be expressed in different tissues of the same organism as a
result of, for example, alternative splicing of RNA. Alternatively,
isoforms can be encoded by different genes. In the invention,
homologous nucleotide sequences include nucleotide sequences
encoding for A NOVX polypeptide of species other than humans,
including, but not limited to vertebrates, and thus can include,
e.g., frog, mouse, rat, rabbit, dog, cat, cow, horse, and other
organisms. Homologous nucleotide sequences also include, but are
not limited to, naturally occurring allelic variations and
mutations of the nucleotide sequences set forth herein. A
homologous nucleotide sequence does not, however, include the exact
nucleotide sequence encoding a human NOVX protein. Homologous
nucleic acid sequences include those nucleic acid sequences that
encode conservative amino acid substitutions (see below) in SEQ ID
NOS:2n-1, wherein n is an integer between 1 and 54, as well as a
polypeptide possessing NOVX biological activity. Various biological
activities of the NOVX proteins are described below.
[0060] A NOVX polypeptide is encoded by the open reading frame
("ORF") of a NOVX nucleic acid. An ORF corresponds to a nucleotide
sequence that could potentially be translated into a polypeptide. A
stretch of nucleic acids comprising an ORF is uninterrupted by a
stop codon. An ORF that represents the coding sequence for a full
protein begins with an ATG "start" codon and terminates with one of
the three "stop" codons, namely, TAA, TAG, or TGA. For the purposes
of this invention, an ORF may be any part of a coding sequence,
with or without a start codon, a stop codon, or both. For an ORF to
be considered as a good candidate for coding for a bona fide
cellular protein, a minimum size requirement is often set, e.g., a
stretch of DNA that would encode a protein of 50 amino acids or
more.
[0061] The nucleotide sequences determined from the cloning of the
human NOVX genes allows for the generation of probes and primers
designed for use in identifying and/or cloning NOVX homologues in
other cell types, e.g. from other tissues, as well as NOVX
homologues from other vertebrates. The probe/primer typically
comprises a substantially purified oligonucleotide. The
oligonucleotide typically comprises a region of nucleotide sequence
that hybridizes under stringent conditions to at least about 12,
25, 50, 100, 150, 200, 250, 300, 350 or 400 consecutive sense
strand nucleotide sequence of SEQ ID NOS:2n-1, wherein n is an
integer between 1 and 54; or an anti-sense strand nucleotide
sequence of SEQ ID NOS:2n-1, wherein n is an integer between 1 and
54; or of a naturally occurring mutant of SEQ ID NOS:2n-1, wherein
n is an integer between 1 and 54.
[0062] Probes based on the human NOVX nucleotide sequences can be
used to detect transcripts or genomic sequences encoding the same
or homologous proteins. In various embodiments, the probe has a
detectable label attached, e.g. the label can be a radioisotope, a
fluorescent compound, an enzyme, or an enzyme co-factor. Such
probes can be used as a part of a diagnostic test kit for
identifying cells or tissues which mis-express A NOVX protein, such
as by measuring a level of A NOVX-encoding nucleic acid in a sample
of cells from a subject e.g., detecting NOVX mRNA levels or
determining whether a genomic NOVX gene has been mutated or
deleted.
[0063] "A polypeptide having a biologically-active portion of A
NOVX polypeptide" refers to polypeptides exhibiting activity
similar, but not necessarily identical, an activity of a
polypeptide of the invention, including mature forms, as measured
in a particular biological assay, with or without dose dependency.
A nucleic acid fragment encoding a "biologically-active portion of
NOVX" can be prepared by isolating a portion SEQ ID NOS:2n-1,
wherein n is an integer between 1 and 54, that encodes a
polypeptide having A NOVX biological activity (the biological
activities of the NOVX proteins are described below), expressing
the encoded portion of NOVX protein (e.g., by recombinant
expression in vitro) and assessing the activity of the encoded
portion of NOVX.
[0064] NOVX Nucleic Acid and Polypeptide Variants
[0065] The invention further encompasses nucleic acid molecules
that differ from the nucleotide sequences shown in SEQ ID NOS:2n-1,
wherein n is an integer between 1 and 54, due to degeneracy of the
genetic code and thus encode the same NOVX proteins as that encoded
by the nucleotide sequences shown in SEQ ID NOS:2n-1, wherein n is
an integer between 1 and 54. In another embodiment, an isolated
nucleic acid molecule of the invention has a nucleotide sequence
encoding a protein having an amino acid sequence shown in SEQ ID
NOS:2n, wherein n is an integer between 1 and 54.
[0066] In addition to the human NOVX nucleotide sequences shown in
SEQ ID NOS:2n-1, wherein n is an integer between 1 and 54, it will
be appreciated by those skilled in the art that DNA sequence
polymorphisms that lead to changes in the amino acid sequences of
the NOVX polypeptides may exist within a population (e.g., the
human population). Such genetic polymorphism in the NOVX genes may
exist among individuals within a population due to natural allelic
variation. As used herein, the terms "gene" and "recombinant gene"
refer to nucleic acid molecules comprising an open reading frame
(ORF) encoding A NOVX protein, preferably a vertebrate NOVX
protein. Such natural allelic variations can typically result in
1-5% variance in the nucleotide sequence of the NOVX genes. Any and
all such nucleotide variations and resulting amino acid
polymorphisms in the NOVX polypeptides, which are the result of
natural allelic variation and that do not alter the functional
activity of the NOVX polypeptides, are intended to be within the
scope of the invention.
[0067] Moreover, nucleic acid molecules encoding NOVX proteins from
other species, and thus that have a nucleotide sequence that
differs from the human SEQ ID NOS:2n-1, wherein n is an integer
between 1 and 54, are intended to be within the scope of the
invention. Nucleic acid molecules corresponding to natural allelic
variants and homologues of the NOVX cDNAs of the invention can be
isolated based on their homology to the human NOVX nucleic acids
disclosed herein using the human cDNAs, or a portion thereof, as a
hybridization probe according to standard hybridization techniques
under stringent hybridization conditions.
[0068] Accordingly, in another embodiment, an isolated nucleic acid
molecule of the invention is at least 6 nucleotides in length and
hybridizes under stringent conditions to the nucleic acid molecule
comprising the nucleotide sequence of SEQ ID NOS:2n-1, wherein n is
an integer between 1 and 54. In another embodiment, the nucleic
acid is at least 10, 25, 50, 100, 250, 500, 750, 1000, 1500, 2000
or more nucleotides in length. In yet another embodiment, an
isolated nucleic acid molecule of the invention hybridizes to the
coding region. As used herein, the term "hybridizes under stringent
conditions" is intended to describe conditions for hybridization
and washing under which nucleotide sequences at least about 65%
homologous to each other typically remain hybridized to each
other.
[0069] Homologs (i.e., nucleic acids encoding NOVX proteins derived
from species other than human) or other related sequences (e.g.,
paralogs) can be obtained by low, moderate or high stringency
hybridization with all or a portion of the particular human
sequence as a probe using methods well known in the art for nucleic
acid hybridization and cloning.
[0070] As used herein, the phrase "stringent hybridization
conditions" refers to conditions under which a probe, primer or
oligonucleotide will hybridize to its target sequence, but to no
other sequences. Stringent conditions are sequence-dependent and
will be different in different circumstances. Longer sequences
hybridize specifically at higher temperatures than shorter
sequences. Generally, stringent conditions are selected to be about
5.degree. C. lower than the thermal melting point (Tm) for the
specific sequence at a defined ionic strength and pH. The Tm is the
temperature (under defined ionic strength, pH and nucleic acid
concentration) at which 50% of the probes complementary to the
target sequence hybridize to the target sequence at equilibrium.
Since the target sequences are generally present at excess at Tm,
50% of the probes are occupied at equilibrium. Typically, stringent
conditions will be those in which the salt concentration is less
than about 1.0 M sodium ion, typically about 0.01 to 1.0 M sodium
ion (or other salts) at pH 7.0 to 8.3 and the temperature is at
least about 30.degree. C. for short probes, primers or
oligonucleotides (e.g., 10 nt to 50 nt) and at least about
60.degree. C. for longer probes, primers and oligonucleotides.
Stringent conditions may also be achieved with the addition of
destabilizing agents, such as formamide.
[0071] Stringent conditions are known to those skilled in the art
and can be found in Ausubel, et al., (eds.), CURRENT PROTOCOLS IN
MOLECULAR BIOLOGY, John Wiley & Sons, N.Y. (1989), 6.3.1-6.3.6.
Preferably, the conditions are such that sequences at least about
65%, 70%, 75%, 85%, 90%, 95%, 98%, or 99% homologous to each other
typically remain hybridized to each other. A non-limiting example
of stringent hybridization conditions are hybridization in a high
salt buffer comprising 6.times.SSC, 50 mM Tris-HCl (pH 7.5), 1 mM
EDTA, 0.02% PVP, 0.02% Ficoll, 0.02% BSA, and 500 mg/ml denatured
salmon sperm DNA at 65.degree. C., followed by one or more washes
in 0.2.times.SSC, 0.01% BSA at 50.degree. C. An isolated nucleic
acid molecule of the invention that hybridizes under stringent
conditions to the sequences SEQ ID NOS:2n-1, wherein n is an
integer between 1 and 54, corresponds to a naturally-occurring
nucleic acid molecule. As used herein, a "naturally-occurring"
nucleic acid molecule refers to an RNA or DNA molecule having a
nucleotide sequence that occurs in nature (e.g., encodes a natural
protein).
[0072] In a second embodiment, a nucleic acid sequence that is
hybridizable to the nucleic acid molecule comprising the nucleotide
sequence of SEQ ID NOS:2n-1, wherein n is an integer between 1 and
54, or fragments, analogs or derivatives thereof, under conditions
of moderate stringency is provided. A non-limiting example of
moderate stringency hybridization conditions are hybridization in
6.times.SSC, 5.times. Denhardt's solution, 0.5% SDS and 100 mg/ml
denatured salmon sperm DNA at 55.degree. C., followed by one or
more washes in 1.times.SSC, 0.1% SDS at 37.degree. C. Other
conditions of moderate stringency that may be used are well-known
within the art. See, e.g., Ausubel, et al. (eds.), 1993, CURRENT
PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, NY, and
Kriegler, 1990; GENE TRANSFER AND EXPRESSION, A LABORATORY MANUAL,
Stockton Press, NY.
[0073] In a third embodiment, a nucleic acid that is hybridizable
to the nucleic acid molecule comprising the nucleotide sequences
SEQ ID NOS:2n-1, wherein n is an integer between 1 and 54, or
fragments, analogs or derivatives thereof, under conditions of low
stringency, is provided. A non-limiting example of low stringency
hybridization conditions are hybridization in 35% formamide,
5.times.SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.02% PVP, 0.02%
Ficoll, 0.2% BSA, 100 mg/ml denatured salmon sperm DNA, 10%
(wt/vol) dextran sulfate at 40.degree. C., followed by one or more
washes in 2.times.SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1%
SDS at 50.degree. C. Other conditions of low stringency that may be
used are well known in the art (e.g., as employed for cross-species
hybridizations). See, e.g., Ausubel, et al. (eds.), 1993, CURRENT
PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, NY, and
Kriegler, 1990, GENE TRANSFER AND EXPRESSION, A LABORATORY MANUAL,
Stockton Press, NY; Shilo and Weinberg, 1981. Proc Natl Acad Sci
USA 78: 6789-6792.
[0074] Conservative Mutations
[0075] In addition to naturally-occurring allelic variants of NOVX
sequences that may exist in the population, the skilled artisan
will further appreciate that changes can be introduced by mutation
into the nucleotide sequences SEQ ID NOS:2n-1, wherein n is an
integer between 1 and 54, thereby leading to changes in the amino
acid sequences of the encoded NOVX proteins, without altering the
functional ability of the NOVX proteins. For example, nucleotide
substitutions leading to amino acid substitutions at
"non-essential" amino acid residues can be made in the sequence SEQ
ID NOS:2n, wherein n is an integer between 1 and 54. A
"non-essential" amino acid residue is a residue that can be altered
from the wild-type sequences of the NOVX proteins without altering
their biological activity, whereas an "essential" amino acid
residue is required for such biological activity. For example,
amino acid residues that are conserved among the NOVX proteins of
the invention are predicted to be particularly non-amenable to
alteration. Amino acids for which conservative substitutions can be
made are well known within the art.
[0076] Another aspect of the invention pertains to nucleic acid
molecules encoding NOVX proteins that contain changes in amino acid
residues that are not essential for activity. Such NOVX proteins
differ in amino acid sequence from SEQ ID NOS:2n-1, wherein n is an
integer between 1 and 54, yet retain biological activity. In one
embodiment, the isolated nucleic acid molecule comprises a
nucleotide sequence encoding a protein, wherein the protein
comprises an amino acid sequence at least about 40 homologous to
the amino acid sequences SEQ ID NOS:2n, wherein n is an integer
between 1 and 54. Preferably, the protein encoded by the nucleic
acid molecule is at least about 60% homologous to SEQ ID NOS:2n,
wherein n is an integer between 1 and 54; more preferably at least
about 70% homologous SEQ ID NOS:2n, wherein n is an integer between
1 and 54; still more preferably at least about 80% homologous to
SEQ ID NOS:2n, wherein n is an integer between 1 and 54; even more
preferably at least about 90% homologous to SEQ ID NOS:2n, wherein
n is an integer between 1 and 54; and most preferably at least
about 95% homologous to SEQ ID NOS:2n, wherein n is an integer
between 1 and 54.
[0077] An isolated nucleic acid molecule encoding A NOVX protein
homologous to the protein of SEQ ID NOS:2n, wherein n is an integer
between 1 and 54, can be created by introducing one or more
nucleotide substitutions, additions or deletions into the
nucleotide sequence of SEQ ID NOS:2n-1, wherein n is an integer
between 1 and 54, such that one or more amino acid substitutions,
additions or deletions are introduced into the encoded protein.
[0078] Mutations can be introduced into SEQ ID NOS:2n-1, wherein n
is an integer between 1 and 54, by standard techniques, such as
site-directed mutagenesis and PCR-mediated mutagenesis. Preferably,
conservative amino acid substitutions are made at one or more
predicted, non-essential amino acid residues. A "conservative amino
acid substitution" is one in which the amino acid residue is
replaced with an amino acid residue having a similar side chain.
Families of amino acid residues having similar side chains have
been defined within the art. These families include amino acids
with basic side chains (e.g., lysine, arginine, histidine), acidic
side chains (e.g., aspartic acid, glutamic acid), uncharged polar
side chains (e.g., glycine, asparagine, glutamine, serine,
threonine, tyrosine, cysteine), nonpolar side chains (e.g.,
alanine, valine, leucine, isoleucine, proline, phenylalanine,
methionine, tryptophan), beta-branched side chains (e.g.,
threonine, valine, isoleucine) and aromatic side chains (e.g.,
tyrosine, phenylalanine, tryptophan, histidine). Thus, a predicted
non-essential amino acid residue in the NOVX protein is replaced
with another amino acid residue from the same side chain family.
Alternatively, in another embodiment, mutations can be introduced
randomly along all or part of A NOVX coding sequence, such as by
saturation mutagenesis, and the resultant mutants can be screened
for NOVX biological activity to identify mutants that retain
activity. Following mutagenesis SEQ ID NOS:2n-1, wherein n is an
integer between 1 and 54, the encoded protein can be expressed by
any recombinant technology known in the art and the activity of the
protein can be determined.
[0079] The relatedness of amino acid families may also be
determined based on side chain interactions. Substituted amino
acids may be fully conserved "strong" residues or fully conserved
"weak" residues. The "strong" group of conserved amino acid
residues may be any one of the following groups: STA, NEQK, NHQK,
NDEQ, QHRK, MILV, MILF, HY, FYW, wherein the single letter amino
acid codes are grouped by those amino acids that may be substituted
for each other. Likewise, the "weak" group of conserved residues
may be any one of the following: CSA, ATV, SAG, STNK, STPA, SGND,
SNDEQK, NDEQHK, NEQHRK, HFY, wherein the letters within each group
represent the single letter amino acid code.
[0080] In one embodiment, a mutant NOVX protein can be assayed for
(i) the ability to form protein:protein interactions with other
NOVX proteins, other cell-surface proteins, or biologically-active
portions thereof, (ii) complex formation between a mutant NOVX
protein and A NOVX ligand; or (iii) the ability of a mutant NOVX
protein to bind to an intracellular target protein or
biologically-active portion thereof; (e.g. avidin proteins).
[0081] In yet another embodiment, a mutant NOVX protein can be
assayed for the ability to regulate a specific biological function
(e.g., regulation of insulin release).
[0082] Antisense Nucleic Acids
[0083] Another aspect of the invention pertains to isolated
antisense nucleic acid molecules that are hybridizable to or
complementary to the nucleic acid molecule comprising the
nucleotide sequence of SEQ ID NOS:2n-1, wherein n is an integer
between 1 and 54, or fragments, analogs or derivatives thereof. An
"antisense" nucleic acid comprises a nucleotide sequence that is
complementary to a "sense" nucleic acid encoding a protein (e.g.,
complementary to the coding strand of a double-stranded cDNA
molecule or complementary to an mRNA sequence). In specific
aspects, antisense nucleic acid molecules are provided that
comprise a sequence complementary to at least about 10, 25, 50,
100, 250 or 500 nucleotides or an entire NOVX coding strand, or to
only a portion thereof. Nucleic acid molecules encoding fragments,
homologs, derivatives and analogs of A NOVX protein of SEQ ID
NOS:2n, wherein n is an integer between 1 and 54, or antisense
nucleic acids complementary to A NOVX nucleic acid sequence of SEQ
ID NOS:2n-1, wherein n is an integer between 1 and 54, are
additionally provided.
[0084] In one embodiment, an antisense nucleic acid molecule is
antisense to a "coding region" of the coding strand of a nucleotide
sequence encoding A NOVX protein. The term "coding region" refers
to the region of the nucleotide sequence comprising codons, which
are translated into amino acid residues. In another embodiment, the
antisense nucleic acid molecule is antisense to a "noncoding
region" of the coding strand of a nucleotide sequence encoding the
NOVX protein. The term "noncoding region" refers to 5' and 3'
sequences, which flank the coding region that are not translated
into amino acids (i.e., also referred to as 5' and 3' untranslated
regions).
[0085] Given the coding strand sequences encoding the NOVX protein
disclosed herein, antisense nucleic acids of the invention can be
designed according to the rules of Watson and Crick or Hoogsteen
base pairing. The antisense nucleic acid molecule can be
complementary to the entire coding region of NOVX mRNA, but more
preferably is an oligonucleotide that is antisense to only a
portion of the coding or noncoding region of NOVX mRNA. For
example, the antisense oligonucleotide can be complementary to the
region surrounding the translation start site of NOVX mRNA. An
antisense oligonucleotide can be, for example, about 5, 10, 15, 20,
25, 30, 35, 40, 45 or 50 nucleotides in length. An antisense
nucleic acid of the invention can be constructed using chemical
synthesis or enzymatic ligation reactions using procedures known in
the art. For example, an antisense nucleic acid (e.g., an antisense
oligonucleotide) can be chemically synthesized using naturally
occurring nucleotides or variously modified nucleotides designed to
increase the biological stability of the molecules or to increase
the physical stability of the duplex formed between the antisense
and sense nucleic acids (e.g., phosphorothioate derivatives and
acridine substituted nucleotides can be used).
[0086] Examples of modified nucleotides that can be used to
generate the antisense nucleic acid include: 5-fluorouracil,
5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine,
xanthine, 4-acetylcytosine, 5-(carboxyhydroxylmethyl) uracil,
beta-D-mannosylqueosine, 5-carboxymethylaminomethyl-2-thiouridine,
5-carboxymethylaminomethyluracil, dihydrouracil,
beta-D-galactosylqueosine, inosine, N6-isopentenyladenine,
1-methylguanine, 1-methylinosine, 2,2-dimethylguanine,
2-methyladenine, 2-methylguanine, 3-methylcytosine,
5-methylcytosine, N6-adenine, 7-methylguanine,
5-methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil,
5'-methoxycarboxymethyluracil, 5-methoxyuracil,
2-methylthio-N-6-isopentenyladenine, uracil-5-oxyacetic acid (v),
wybutoxosine, pseudouracil, queosine, 2-thiocytosine,
5-methyl-2-thiouracil, 2-thiouracil, 4-thiouracil, 5-methyluracil,
uracil-5-oxyacetic acid methylester, uracil-5-oxyacetic acid (v),
5-methyl-2-thiouracil, 3-(3-amino-3-N-2-carboxypropyl) uracil,
(acp3)w, and 2,6-diaminopurine. Alternatively, the antisense
nucleic acid can be produced biologically using an expression
vector into which a nucleic acid has been subcloned in an antisense
orientation (i.e., RNA transcribed from the inserted nucleic acid
will be of an antisense orientation to a target nucleic acid of
interest, described further in the following subsection).
[0087] The antisense nucleic acid molecules of the invention are
typically administered to a subject or generated in situ such that
they hybridize with or bind to cellular mRNA and/or genomic DNA
encoding A NOVX protein to thereby inhibit expression of the
protein (e.g., by inhibiting transcription and/or translation). The
hybridization can be by conventional nucleotide complementarity to
form a stable duplex, or, for example, in the case of an antisense
nucleic acid molecule that binds to DNA duplexes, through specific
interactions in the major groove of the double helix. An example of
a route of administration of antisense nucleic acid molecules of
the invention includes direct injection at a tissue site.
Alternatively, antisense nucleic acid molecules can be modified to
target selected cells and then administered systemically. For
example, for systemic administration, antisense molecules can be
modified such that they specifically bind to receptors or antigens
expressed on a selected cell surface (e.g., by linking the
antisense nucleic acid molecules to peptides or antibodies that
bind to cell surface receptors or antigens). The antisense nucleic
acid molecules can also be delivered to cells using the vectors
described herein. To achieve sufficient nucleic acid molecules,
vector constructs in which the antisense nucleic acid molecule is
placed under the control of a strong pol II or pol III promoter are
preferred.
[0088] In yet another embodiment, the antisense nucleic acid
molecule of the invention is an .alpha.-anomeric nucleic acid
molecule. A .alpha.-anomeric nucleic acid molecule forms specific
double-stranded hybrids with complementary RNA in which, contrary
to the usual .beta.-units, the strands run parallel to each other.
See, e.g., Gaultier, et al., 1987. Nucl. Acids Res. 15: 6625-6641.
The antisense nucleic acid molecule can also comprise a
2'-o-methylribonucleotide (See, e.g., Inoue, et al. 1987. Nucl.
Acids Res. 15: 6131-6148) or a chimeric RNA-DNA analogue (See,
e.g., Inoue, et al., 1987. FEBS Lett. 215: 327-330.
[0089] Ribozymes and PNA Moieties
[0090] Nucleic acid modifications include, by way of non-limiting
example, modified bases, and nucleic acids whose sugar phosphate
backbones are modified or derivatized. These modifications are
carried out at least in part to enhance the chemical stability of
the modified nucleic acid, such that they may be used, for example,
as antisense binding nucleic acids in therapeutic applications in a
subject.
[0091] In one embodiment, an antisense nucleic acid of the
invention is a ribozyme. Ribozymes are catalytic RNA molecules with
ribonuclease activity that are capable of cleaving a
single-stranded nucleic acid, such as an mRNA, to which they have a
complementary region. Thus, ribozymes (e.g., hammerhead ribozymes
as described in Haselhoff and Gerlach 1988. Nature 334: 585-591)
can be used to catalytically cleave NOVX mRNA transcripts to
thereby inhibit translation of NOVX mRNA. A ribozyme having
specificity for a NOVX-encoding nucleic acid can be designed based
upon the nucleotide sequence of A NOVX cDNA disclosed herein (i.e.,
SEQ ID NOS:2n-1, wherein n is an integer between 1 and 54). For
example, a derivative of a Tetrahymena L-19 IVS RNA can be
constructed in which the nucleotide sequence of the active site is
complementary to the nucleotide sequence to be cleaved in a
NOVX-encoding mRNA. See, e.g., U.S. Pat. No. 4,987,071 to Cech, et
al. and U.S. Pat. No. 5,116,742 to Cech, et al. NOVX mRNA can also
be used to select a catalytic RNA having a specific ribonuclease
activity from a pool of RNA molecules. See, e.g., Bartel et al.,
(1993) Science 261:1411-1418.
[0092] Alternatively, NOVX gene expression can be inhibited by
targeting nucleotide sequences complementary to the regulatory
region of the NOVX nucleic acid (e.g., the NOVX promoter and/or
enhancers) to form triple helical structures that prevent
transcription of the NOVX gene in target cells. See, e.g., Helene,
1991. Anticancer Drug Des. 6: 569-84; Helene, et al. 1992. Ann.
N.Y. Acad. Sci. 660: 27-36; Maher, 1992. Bioassays 14: 807-15.
[0093] In various embodiments, the NOVX nucleic acids can be
modified at the base moiety, sugar moiety or phosphate backbone to
improve, e.g., the stability, hybridization, or solubility of the
molecule. For example, the deoxyribose phosphate backbone of the
nucleic acids can be modified to generate peptide nucleic acids.
See, e.g., Hyrup, et al., 1996. Bioorg Med Chem 4: 5-23. As used
herein, the terms "peptide nucleic acids" or "PNAs" refer to
nucleic acid mimics (e.g., DNA mimics) in which the deoxyribose
phosphate backbone is replaced by a pseudopeptide backbone and only
the four natural nucleobases are retained. The neutral backbone of
PNAs has been shown to allow for specific hybridization to DNA and
RNA under conditions of low ionic strength. The synthesis of PNA
oligomers can be performed using standard solid phase peptide
synthesis protocols as described in Hyrup, et al., 1996. supra;
Perry-O'Keefe, et al., 1996. Proc. Natl. Acad. Sci. USA 93:
14670-14675.
[0094] PNAs of NOVX can be used in therapeutic and diagnostic
applications. For example, PNAs can be used as antisense or
antigene agents for sequence-specific modulation of gene expression
by, e.g., inducing transcription or translation arrest or
inhibiting replication. PNAs of NOVX can also be used, for example,
in the analysis of single base pair mutations in a gene (e.g., PNA
directed PCR clamping; as artificial restriction enzymes when used
in combination with other enzymes, e.g., S.sub.1 nucleases (See,
Hyrup, et al., 1996 supra); or as probes or primers for DNA
sequence and hybridization (See, Hyrup, et al., 1996, supra;
Perry-O'Keefe, et al., 1996. supra).
[0095] In another embodiment, PNAs of NOVX can be modified, e.g.,
to enhance their stability or cellular uptake, by attaching
lipophilic or other helper groups to PNA, by the formation of
PNA-DNA chimeras, or by the use of liposomes or other techniques of
drug delivery known in the art. For example, PNA-DNA chimeras of
NOVX can be generated that may combine the advantageous properties
of PNA and DNA. Such chimeras allow DNA recognition enzymes (e.g.,
RNase H and DNA polymerases) to interact with the DNA portion while
the PNA portion would provide high binding affinity and
specificity. PNA-DNA chimeras can be linked using linkers of
appropriate lengths selected in terms of base stacking, number of
bonds between the nucleobases, and orientation (see, Hyrup, et al.,
1996. supra). The synthesis of PNA-DNA chimeras can be performed as
described in Hyrup, et al., 1996. supra and Finn, et al., 1996.
Nucl Acids Res 24: 3357-3363. For example, a DNA chain can be
synthesized on a solid support using standard phosphoramidite
coupling chemistry, and modified nucleoside analogs, e.g.,
5'-(4-methoxytrityl)amino-5'-deoxy-thymidine phosphoramidite, can
be used between the PNA and the 5' end of DNA. See, e.g., Mag, et
al., 1989. Nucl Acid Res 17: 5973-5988. PNA monomers are then
coupled in a stepwise manner to produce a chimeric molecule with a
5' PNA segment and a 3' DNA segment. See, e.g., Finn, et al., 1996.
supra. Alternatively, chimeric molecules can be synthesized with a
5' DNA segment and a 3' PNA segment. See, e.g., Petersen, et al.,
1975. Bioorg. Med. Chem. Lett. 5: 1119-11124.
[0096] In other embodiments, the oligonucleotide may include other
appended groups such as peptides (e.g., for targeting host cell
receptors in vivo), or agents facilitating transport across the
cell membrane (see, e.g., Letsinger, et al., 1989. Proc. Natl.
Acad. Sci. U.S.A. 86: 6553-6556; Lemaitre, et al., 1987. Proc.
Natl. Acad. Sci. 84: 648-652; PCT Publication No. WO88/09810) or
the blood-brain barrier (see, e.g., PCT Publication No. WO
89/10134). In addition, oligonucleotides can be modified with
hybridization triggered cleavage agents (see, e.g., Krol, et al.,
1988. BioTechniques 6:958-976) or intercalating agents (see, e.g.,
Zon, 1988. Pharm. Res. 5: 539-549). To this end, the
oligonucleotide may be conjugated to another molecule, e.g., a
peptide, a hybridization triggered cross-linking agent, a transport
agent, a hybridization-triggered cleavage agent, and the like.
[0097] NOVX Polypeptides
[0098] A polypeptide according to the invention includes a
polypeptide including the amino acid sequence of NOVX polypeptides
whose sequences are provided in SEQ ID NOS:2n, wherein n is an
integer between 1 and 54. The invention also includes a mutant or
variant protein any of whose residues may be changed from the
corresponding residues shown in SEQ ID NOS:2n, wherein n is an
integer between 1 and 54, while still encoding a protein that
maintains its NOVX activities and physiological functions, or a
functional fragment thereof.
[0099] In general, A NOVX variant that preserves NOVX-like function
includes any variant in which residues at a particular position in
the sequence have been substituted by other amino acids, and
further include the possibility of inserting an additional residue
or residues between two residues of the parent protein as well as
the possibility of deleting one or more residues from the parent
sequence. Any amino acid substitution, insertion, or deletion is
encompassed by the invention. In favorable circumstances, the
substitution is a conservative substitution as defined above.
[0100] One aspect of the invention pertains to isolated NOVX
proteins, and biologically-active portions thereof, or derivatives,
fragments, analogs or homologs thereof. Also provided are
polypeptide fragments suitable for use as immunogens to raise
anti-NOVX antibodies. In one embodiment, native NOVX proteins can
be isolated from cells or tissue sources by an appropriate
purification scheme using standard protein purification techniques.
In another embodiment, NOVX proteins are produced by recombinant
DNA techniques. Alternative to recombinant expression, A NOVX
protein or polypeptide can be synthesized chemically using standard
peptide synthesis techniques.
[0101] An "isolated" or "purified" polypeptide or protein or
biologically-active portion thereof is substantially free of
cellular material or other contaminating proteins from the cell or
tissue source from which the NOVX protein is derived, or
substantially free from chemical precursors or other chemicals when
chemically synthesized. The language "substantially free of
cellular material" includes preparations of NOVX proteins in which
the protein is separated from cellular components of the cells from
which it is isolated or recombinantly-produced. In one embodiment,
the language "substantially free of cellular material" includes
preparations of NOVX proteins having less than about 30% (by dry
weight) of non-NOVX proteins (also referred to herein as a
"contaminating protein"), more preferably less than about 20% of
non-NOVX proteins, still more preferably less than about 10% of
non-NOVX proteins, and most preferably less than about 5% of
non-NOVX proteins. When the NOVX protein or biologically-active
portion thereof is recombinantly-produced, it is also preferably
substantially free of culture medium, i.e., culture medium
represents less than about 20%, more preferably less than about
10%, and most preferably less than about 5% of the volume of the
NOVX protein preparation.
[0102] The language "substantially free of chemical precursors or
other chemicals" includes preparations of NOVX proteins in which
the protein is separated from chemical precursors or other
chemicals that are involved in the synthesis of the protein. In one
embodiment, the language "substantially free of chemical precursors
or other chemicals" includes preparations of NOVX proteins having
less than about 30% (by dry weight) of chemical precursors or
non-NOVX chemicals, more preferably less than about 20% chemical
precursors or non-NOVX chemicals, still more preferably less than
about 10% chemical precursors or non-NOVX chemicals, and most
preferably less than about 5% chemical precursors or non-NOVX
chemicals.
[0103] Biologically-active portions of NOVX proteins include
peptides comprising amino acid sequences sufficiently homologous to
or derived from the amino acid sequences of the NOVX proteins
(e.g., the amino acid sequence shown in SEQ ID NOS:2n, wherein n is
an integer between 1 and 54) that include fewer amino acids than
the full-length NOVX proteins, and exhibit at least one activity of
A NOVX protein. Typically, biologically-active portions comprise a
domain or motif with at least one activity of the NOVX protein. A
biologically-active portion of A NOVX protein can be a polypeptide
which is, for example, 10, 25, 50, 100 or more amino acid residues
in length.
[0104] Moreover, other biologically-active portions, in which other
regions of the protein are deleted, can be prepared by recombinant
techniques and evaluated for one or more of the functional
activities of a native NOVX protein.
[0105] In an embodiment, the NOVX protein has an amino acid
sequence shown SEQ ID NOS:2n, wherein n is an integer between 1 and
54. In other embodiments, the NOVX protein is substantially
homologous to SEQ ID NOS:2n, wherein n is an integer between 1 and
54, and retains the functional activity of the protein of SEQ ID
NOS:2n, wherein n is an integer between 1 and 54, yet differs in
amino acid sequence due to natural allelic variation or
mutagenesis, as described in detail, below. Accordingly, in another
embodiment, the NOVX protein is a protein that comprises an amino
acid sequence at least about 45% homologous to the amino acid
sequence SEQ ID NOS:2n, wherein n is an integer between 1 and 54,
and retains the functional activity of the NOVX proteins of SEQ ID
NOS:2n, wherein n is an integer between 1 and 54.
[0106] Determining Homology Between Two or More Sequences
[0107] To determine the percent homology of two amino acid
sequences or of two nucleic acids, the sequences are aligned for
optimal comparison purposes (e.g., gaps can be introduced in the
sequence of a first amino acid or nucleic acid sequence for optimal
alignment with a second amino or nucleic acid sequence). The amino
acid residues or nucleotides at corresponding amino acid positions
or nucleotide positions are then compared. When a position in the
first sequence is occupied by the same amino acid residue or
nucleotide as the corresponding position in the second sequence,
then the molecules are homologous at that position (i.e., as used
herein amino acid or nucleic acid "homology" is equivalent to amino
acid or nucleic acid "identity").
[0108] The nucleic acid sequence homology may be determined as the
degree of identity between two sequences. The homology may be
determined using computer programs known in the art, such as GAP
software provided in the GCG program package. See, Needleman and
Wunsch, 1970. J Mol Biol 48: 443-453. Using GCG GAP software with
the following settings for nucleic acid sequence comparison: GAP
creation penalty of 5.0 and GAP extension penalty of 0.3, the
coding region of the analogous nucleic acid sequences referred to
above exhibits a degree of identity preferably of at least 70%,
75%, 80%, 85%, 90%, 95%, 98%, or 99%, with the CDS (encoding) part
of the DNA sequence shown in SEQ ID NOS:2n-1, wherein n is an
integer between 1 and 54.
[0109] The term "sequence identity" refers to the degree to which
two polynucleotide or polypeptide sequences are identical on a
residue-by-residue basis over a particular region of comparison.
The term "percentage of sequence identity" is calculated by
comparing two optimally aligned sequences over that region of
comparison, determining the number of positions at which the
identical nucleic acid base (e.g., A, T, C, G, U, or I, in the case
of nucleic acids) occurs in both sequences to yield the number of
matched positions, dividing the number of matched positions by the
total number of positions in the region of comparison (i.e., the
window size), and multiplying the result by 100 to yield the
percentage of sequence identity. The term "substantial identity" as
used herein denotes a characteristic of a polynucleotide sequence,
wherein the polynucleotide comprises a sequence that has at least
80 percent sequence identity, preferably at least 85 percent
identity and often 90 to 95 percent sequence identity, more usually
at least 99 percent sequence identity as compared to a reference
sequence over a comparison region.
[0110] Chimeric and Fusion Proteins
[0111] The invention also provides NOVX chimeric or fusion
proteins. As used herein, A NOVX "chimeric protein" or "fusion
protein" comprises A NOVX polypeptide operatively-linked to a
non-NOVX polypeptide. An "NOVX polypeptide" refers to a polypeptide
having an amino acid sequence corresponding to A NOVX protein SEQ
ID NOS:2n, wherein n is an integer between 1 and 54, whereas a
"non-NOVX polypeptide" refers to a polypeptide having an amino acid
sequence corresponding to a protein that is not substantially
homologous to the NOVX protein, e.g., a protein that is different
from the NOVX protein and that is derived from the same or a
different organism. Within A NOVX fusion protein the NOVX
polypeptide can correspond to all or a portion of A NOVX protein.
In one embodiment, A NOVX fusion protein comprises at least one
biologically active portion of A NOVX protein. In another
embodiment, A NOVX fusion protein comprises at least two
biologically active portions of A NOVX protein. In yet another
embodiment, A NOVX fusion protein comprises at least three
biologically active portions of A NOVX protein. Within the fusion
protein, the term "operatively-linked" is intended to indicate that
the NOVX polypeptide and the non-NOVX polypeptide are fused
in-frame with one another. The non-NOVX polypeptide can be fused to
the N-terminus or C-terminus of the NOVX polypeptide.
[0112] In one embodiment, the fusion protein is a GST-NOVX fusion
protein in which the NOVX sequences are fused to the C-terminus of
the GST (glutathione S-transferase) sequences. Such fusion proteins
can facilitate the purification of recombinant NOVX
polypeptides.
[0113] In another embodiment, the fusion protein is A NOVX protein
containing a heterologous signal sequence at its N-terminus. In
certain host cells (e.g., mammalian host cells), expression and/or
secretion of NOVX can be increased through use of a heterologous
signal sequence.
[0114] In yet another embodiment, the fusion protein is a
NOVX-immunoglobulin fusion protein in which the NOVX sequences are
fused to sequences derived from a member of the immunoglobulin
protein family. The NOVX-immunoglobulin fusion proteins of the
invention can be incorporated into pharmaceutical compositions and
administered to a subject to inhibit an interaction between A NOVX
ligand and A NOVX protein on the surface of a cell, to thereby
suppress NOVX-mediated signal transduction in vivo. The
NOVX-immunoglobulin fusion proteins can be used to affect the
bioavailability of A NOVX cognate ligand. Inhibition of the NOVX
ligand/NOVX interaction may be useful therapeutically for both the
treatment of proliferative and differentiative disorders, as well
as modulating (e.g. promoting or inhibiting) cell survival.
Moreover, the NOVX-immunoglobulin fusion proteins of the invention
can be used as immunogens to produce anti-NOVX antibodies in a
subject, to purify NOVX ligands, and in screening assays to
identify molecules that inhibit the interaction of NOVX with A NOVX
ligand.
[0115] A NOVX chimeric or fusion protein of the invention can be
produced by standard recombinant DNA techniques. For example, DNA
fragments coding for the different polypeptide sequences are
ligated together in-frame in accordance with conventional
techniques, e.g., by employing blunt-ended or stagger-ended termini
for ligation, restriction enzyme digestion to provide for
appropriate termini, filling-in of cohesive ends as appropriate,
alkaline phosphatase treatment to avoid undesirable joining, and
enzymatic ligation. In another embodiment, the fusion gene can be
synthesized by conventional techniques including automated DNA
synthesizers. Alternatively, PCR amplification of gene fragments
can be carried out using anchor primers that give rise to
complementary overhangs between two consecutive gene fragments that
can subsequently be annealed and reamplified to generate a chimeric
gene sequence (see, e.g., Ausubel, et al. (eds.) CURRENT PROTOCOLS
IN MOLECULAR BIOLOGY, John Wiley & Sons, 1992). Moreover, many
expression vectors are commercially available that already encode a
fusion moiety (e.g., a GST polypeptide). A NOVX-encoding nucleic
acid can be cloned into such an expression vector such that the
fusion moiety is linked in-frame to the NOVX protein.
NOVX Agonists and Antagonists
[0116] The invention also pertains to variants of the NOVX proteins
that function as either NOVX agonists (i.e., mimetics) or as NOVX
antagonists. Variants of the NOVX protein can be generated by
mutagenesis (e.g., discrete point mutation or truncation of the
NOVX protein). An agonist of the NOVX protein can retain
substantially the same, or a subset of, the biological activities
of the naturally occurring form of the NOVX protein. An antagonist
of the NOVX protein can inhibit one or more of the activities of
the naturally occurring form of the NOVX protein by, for example,
competitively binding to a downstream or upstream member of a
cellular signaling cascade, which includes the NOVX protein. Thus,
specific biological effects can be elicited by treatment with a
variant of limited function. In one embodiment, treatment of a
subject with a variant having a subset of the biological activities
of the naturally occurring form of the protein has fewer side
effects in a subject relative to treatment with the naturally
occurring form of the NOVX proteins.
[0117] Variants of the NOVX proteins that function as either NOVX
agonists (i.e., mimetics) or as NOVX antagonists can be identified
by screening combinatorial libraries of mutants (e.g., truncation
mutants) of the NOVX proteins for NOVX protein agonist or
antagonist activity. In one embodiment, a variegated library of
NOVX variants is generated by combinatorial mutagenesis at the
nucleic acid level and is encoded by a variegated gene library. A
variegated library of NOVX variants can be produced by, for
example, enzymatically ligating a mixture of synthetic
oligonucleotides into gene sequences such that a degenerate set of
potential NOVX sequences is expressible as individual polypeptides,
or alternatively, as a set of larger fusion proteins (e.g., for
phage display) containing the set of NOVX sequences therein. There
are a variety of methods, which can be used to produce libraries of
potential NOVX variants from a degenerate oligonucleotide sequence.
Chemical synthesis of a degenerate gene sequence can be performed
in an automatic DNA synthesizer, and the synthetic gene then
ligated into an appropriate expression vector. Use of a degenerate
set of genes allows for the provision, in one mixture, of all of
the sequences encoding the desired set of potential NOVX sequences.
Methods for synthesizing degenerate oligonucleotides are well known
within the art. See, e.g., Narang, 1983. Tetrahedron 39: 3;
Itakura, et al., 1984. Annu. Rev. Biochem. 53: 323; Itakura, et
al., 1984. Science 198: 1056; Ike, et al., 1983. Nucl. Acids Res.
11:477.
[0118] Polypeptide Libraries
[0119] In addition, libraries of fragments of the NOVX protein
coding sequences can be used to generate a variegated population of
NOVX fragments for screening and subsequent selection of variants
of A NOVX protein. In one embodiment, a library of coding sequence
fragments can be generated by treating a double stranded PCR
fragment of A NOVX coding sequence with a nuclease under conditions
wherein nicking occurs only about once per molecule, denaturing the
double stranded DNA, renaturing the DNA to form double-stranded DNA
that can include sense/antisense pairs from different nicked
products, removing single stranded portions from reformed duplexes
by treatment with S.sub.1 nuclease, and ligating the resulting
fragment library into an expression vector. By this method,
expression libraries can be derived which encodes N-terminal and
internal fragments of various sizes of the NOVX proteins.
[0120] Various techniques are known in the art for screening gene
products of combinatorial libraries made by point mutations or
truncation, and for screening cDNA libraries for gene products
having a selected property. Such techniques are adaptable for rapid
screening of the gene libraries generated by the combinatorial
mutagenesis of NOVX proteins. The most widely used techniques,
which are amenable to high throughput analysis, for screening large
gene libraries typically include cloning the gene library into
replicable expression vectors, transforming appropriate cells with
the resulting library of vectors, and expressing the combinatorial
genes under conditions in which detection of a desired activity
facilitates isolation of the vector encoding the gene whose product
was detected. Recursive ensemble mutagenesis (REM), a new technique
that enhances the frequency of functional mutants in the libraries,
can be used in combination with the screening assays to identify
NOVX variants. See, e.g., Arkin and Yourvan, 1992. Proc. Natl.
Acad. Sci. USA 89: 7811-7815; Delgrave, et al., 1993. Protein
Engineering 6:327-331.
[0121] NOVX Antibodies
[0122] The term "antibody" as used herein refers to immunoglobulin
molecules and immunologically active portions of immunoglobulin
(Ig) molecules, i.e., molecules that contain an antigen-binding
site that specifically binds (immunoreacts with) an antigen. Such
antibodies include, but are not limited to, polyclonal, monoclonal,
chimeric, single chain, F.sub.ab, F.sub.ab, and F.sub.(ab')2
fragments, and an F.sub.ab expression library. In general, antibody
molecules obtained from humans relates to any of the classes IgG,
IgM, IgA, IgE and IgD, which differ from one another by the nature
of the heavy chain present in the molecule. Certain classes have
subclasses as well, such as IgG.sub.1, IgG.sub.2, and others.
Furthermore, in humans, the light chain may be a kappa chain or a
lambda chain. Reference herein to antibodies includes a reference
to all such classes, subclasses and types of human antibody
species.
[0123] An isolated protein of the invention intended to serve as an
antigen, or a portion or fragment thereof, can be used as an
immunogen to generate antibodies that immunospecifically bind the
antigen, using standard techniques for polyclonal and monoclonal
antibody preparation. The full-length protein can be used or,
alternatively, the invention provides antigenic peptide fragments
of the antigen for use as immunogens. An antigenic peptide fragment
comprises at least 6 amino acid residues of the amino acid sequence
of the full length protein, such as an amino acid sequence shown in
SEQ ID NOs: 2n, wherein n is an integer between 1 and 54, and
encompasses an epitope thereof such that an antibody raised against
the peptide forms a specific immune complex with the full length
protein or with any fragment that contains the epitope. Preferably,
the antigenic peptide comprises at least 10 amino acid residues, or
at least 15 amino acid residues, or at least 20 amino acid
residues, or at least 30 amino acid residues. Preferred epitopes
encompassed by the antigenic peptide are regions of the protein
that are located on its surface; commonly these are hydrophilic
regions.
[0124] In certain embodiments of the invention, at least one
epitope encompassed by the antigenic peptide is a region of NOVX
that is located on the surface of the protein, e.g., a hydrophilic
region. A hydrophobicity analysis of the human NOVX protein
sequence will indicate which regions of a NOVX polypeptide are
particularly hydrophilic and, therefore, are likely to encode
surface residues useful for targeting antibody production. As a
means for targeting antibody production, hydropathy plots showing
regions of hydrophilicity and hydrophobicity may be generated by
any method well known in the art, including, for example, the Kyte
Doolittle or the Hopp Woods methods, either with or without Fourier
transformation. See, e.g., Hopp and Woods, 1981, Proc. Nat. Acad.
Sci. USA 78: 3824-3828; Kyte and Doolittle 1982, J. Mol. Biol. 157:
105-142, each incorporated herein by reference in their entirety.
Antibodies that are specific for one or more domains within an
antigenic protein, or derivatives, fragments, analogs or homologs
thereof, are also provided herein.
[0125] A protein of the invention, or a derivative, fragment,
analog, homolog or ortholog thereof, may be utilized as an
immunogen in the generation of antibodies that immunospecifically
bind these protein components.
[0126] Various procedures known within the art may be used for the
production of polyclonal or monoclonal antibodies directed against
a protein of the invention, or against derivatives, fragments,
analogs homologs or orthologs thereof (see, for example,
Antibodies: A Laboratory Manual, Harlow E, and Lane D, 1988, Cold
Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.,
incorporated herein by reference). Some of these antibodies are
discussed below.
[0127] Polyclonal Antibodies
[0128] For the production of polyclonal antibodies, various
suitable host animals (e.g., rabbit, goat, mouse or other mammal)
may be immunized by one or more injections with the native protein,
a synthetic variant thereof, or a derivative of the foregoing. An
appropriate immunogenic preparation can contain, for example, the
naturally occurring immunogenic protein, a chemically synthesized
polypeptide representing the immunogenic protein, or a
recombinantly expressed immunogenic protein. Furthermore, the
protein may be conjugated to a second protein known to be
immunogenic in the mammal being immunized. Examples of such
immunogenic proteins include but are not limited to keyhole limpet
hemocyanin, serum albumin, bovine thyroglobulin, and soybean
trypsin inhibitor. The preparation can further include an adjuvant.
Various adjuvants used to increase the immunological response
include, but are not limited to, Freund's (complete and
incomplete), mineral gels (e.g., aluminum hydroxide), surface
active substances (e.g., lysolecithin, pluronic polyols,
polyanions, peptides, oil emulsions, dinitrophenol, etc.),
adjuvants usable in humans such as Bacille Calmette-Guerin and
Corynebacterium parvum, or similar immunostimulatory agents.
Additional examples of adjuvants which can be employed include
MPL-TDM adjuvant (monophosphoryl Lipid A, synthetic trehalose
dicorynomycolate).
[0129] The polyclonal antibody molecules directed against the
immunogenic protein can be isolated from the mammal (e.g., from the
blood) and further purified by well known techniques, such as
affinity chromatography using protein A or protein G, which provide
primarily the IgG fraction of immune serum. Subsequently, or
alternatively, the specific antigen which is the target of the
immunoglobulin sought, or an epitope thereof, may be immobilized on
a column to purify the immune specific antibody by immunoaffinity
chromatography. Purification of immunoglobulins is discussed, for
example, by D. Wilkinson (The Scientist, published by The
Scientist, Inc., Philadelphia Pa., Vol. 14, No. 8 (Apr. 17, 2000),
pp. 25-28).
[0130] Monoclonal Antibodies
[0131] The term "monoclonal antibody" (MAb) or "monoclonal antibody
composition", as used herein, refers to a population of antibody
molecules that contain only one molecular species of antibody
molecule consisting of a unique light chain gene product and a
unique heavy chain gene product. In particular, the complementarity
determining regions (CDRs) of the monoclonal antibody are identical
in all the molecules of the population. MAbs thus contain an
antigen binding site capable of immunoreacting with a particular
epitope of the antigen characterized by a unique binding affinity
for it.
[0132] Monoclonal antibodies can be prepared using hybridoma
methods, such as those described by Kohler and Milstein, Nature
256:495 (1975). In a hybridoma method, a mouse, hamster, or other
appropriate host animal, is typically immunized with an immunizing
agent to elicit lymphocytes that produce or are capable of
producing antibodies that will specifically bind to the immunizing
agent. Alternatively, the lymphocytes can be immunized in
vitro.
[0133] The immunizing agent will typically include the protein
antigen, a fragment thereof or a fusion protein thereof. Generally,
either peripheral blood lymphocytes are used if cells of human
origin are desired, or spleen cells or lymph node cells are used if
non-human mammalian sources are desired. The lymphocytes are then
fused with an immortalized cell line using a suitable fusing agent,
such as polyethylene glycol, to form a hybridoma cell [Goding,
Monoclonal Antibodies: Principles and Practice, Academic Press,
(1986) pp. 59-103]. Immortalized cell lines are usually transformed
mammalian cells, particularly myeloma cells of rodent, bovine and
human origin. Usually, rat or mouse myeloma cell lines are
employed. The hybridoma cells can be cultured in a suitable culture
medium that preferably contains one or more substances that inhibit
the growth or survival of the unfused, immortalized cells. For
example, if the parental cells lack the enzyme hypoxanthine guanine
phosphoribosyl transferase (HGPRT or HPRT), the culture medium for
the hybridomas typically will include hypoxanthine, aminopterin,
and thymidine ("HAT medium"), which substances prevent the growth
of HGPRT-deficient cells.
[0134] Preferred immortalized cell lines are those that fuse
efficiently, support stable high level expression of antibody by
the selected antibody-producing cells, and are sensitive to a
medium such as HAT medium. More preferred immortalized cell lines
are murine myeloma lines, which can be obtained, for instance, from
the Salk Institute Cell Distribution Center, San Diego, Calif. and
the American Type Culture Collection, Manassas, Va. Human myeloma
and mouse-human heteromyeloma cell lines also have been described
for the production of human monoclonal antibodies [Kozbor, J.
Immunol., 133:3001 (1984); Brodeur et al., Monoclonal Antibody
Production Techniques and Applications, Marcel Dekker, Inc., New
York, (1987) pp. 51-63].
[0135] The culture medium in which the hybridoma cells are cultured
can then be assayed for the presence of monoclonal antibodies
directed against the antigen. Preferably, the binding specificity
of monoclonal antibodies produced by the hybridoma cells is
determined by immunoprecipitation or by an in vitro binding assay,
such as radioimmunoassay (RIA) or enzyme-linked immunoabsorbent
assay (ELISA). Such techniques and assays are known in the art. The
binding affinity of the monoclonal antibody can, for example, be
determined by the Scatchard analysis of Munson and Pollard, Anal.
Biochem., 107:220 (1980). It is an objective, especially important
in therapeutic applications of monoclonal antibodies, to identify
antibodies having a high degree of specificity and a high binding
affinity for the target antigen.
[0136] After the desired hybridoma cells are identified, the clones
can be subcloned by limiting dilution procedures and grown by
standard methods (Goding, 1986). Suitable culture media for this
purpose include, for example, Dulbecco's Modified Eagle's Medium
and RPMI-1640 medium. Alternatively, the hybridoma cells can be
grown in vivo as ascites in a mammal.
[0137] The monoclonal antibodies secreted by the subclones can be
isolated or purified from the culture medium or ascites fluid by
conventional immunoglobulin purification procedures such as, for
example, protein A-Sepharose, hydroxylapatite chromatography, gel
electrophoresis, dialysis, or affinity chromatography.
[0138] The monoclonal antibodies can also be made by recombinant
DNA methods, such as those described in U.S. Pat. No. 4,816,567.
DNA encoding the monoclonal antibodies of the invention can be
readily isolated and sequenced using conventional procedures (e.g.,
by using oligonucleotide probes that are capable of binding
specifically to genes encoding the heavy and light chains of murine
antibodies). The hybridoma cells of the invention serve as a
preferred source of such DNA. Once isolated, the DNA can be placed
into expression vectors, which are then transfected into host cells
such as simian COS cells, Chinese hamster ovary (CHO) cells, or
myeloma cells that do not otherwise produce immunoglobulin protein,
to obtain the synthesis of monoclonal antibodies in the recombinant
host cells. The DNA also can be modified, for example, by
substituting the coding sequence for human heavy and light chain
constant domains in place of the homologous murine sequences (U.S.
Pat. No. 4,816,567; Morrison, Nature 368, 812-13 (1994)) or by
covalently joining to the immunoglobulin coding sequence all or
part of the coding sequence for a non-immunoglobulin polypeptide.
Such a non-immunoglobulin polypeptide can be substituted for the
constant domains of an antibody of the invention, or can be
substituted for the variable domains of one antigen-combining site
of an antibody of the invention to create a chimeric bivalent
antibody.
[0139] Humanized Antibodies
[0140] The antibodies directed against the protein antigens of the
invention can further comprise humanized antibodies or human
antibodies. These antibodies are suitable for administration to
humans without engendering an immune response by the human against
the administered immunoglobulin. Humanized forms of antibodies are
chimeric immunoglobulins, immunoglobulin chains or fragments
thereof (such as Fv, Fab, Fab', F(ab').sub.2 or other
antigen-binding subsequences of antibodies) that are principally
comprised of the sequence of a human immunoglobulin, and contain
minimal sequence derived from a non-human immunoglobulin.
Humanization can be performed following the method of Winter and
co-workers (Jones et al., Nature, 321:522-525 (1986); Riechmann et
al., Nature, 332:323-327 (1988); Verhoeyen et al., Science
239:1534-1536 (1988)), by substituting rodent CDRs or CDR sequences
for the corresponding sequences of a human antibody. (See also U.S.
Pat. No. 5,225,539.) In some instances, Fv framework residues of
the human immunoglobulin are replaced by corresponding non-human
residues. Humanized antibodies can also comprise residues which are
found neither in the recipient antibody nor in the imported CDR or
framework sequences. In general, the humanized antibody will
comprise substantially all of at least one, and typically two,
variable domains, in which all or substantially all of the CDR
regions correspond to those of a non-human immunoglobulin and all
or substantially all of the framework regions are those of a human
immunoglobulin consensus sequence. The humanized antibody optimally
also will comprise at least a portion of an immunoglobulin constant
region (Fc), typically that of a human immunoglobulin (Jones et
al., 1986; Riechmann et al., 1988; and Presta, Curr. Op. Struct.
Biol., 2:593-596 (1992)).
[0141] Human Antibodies
[0142] Fully human antibodies essentially relate to antibody
molecules in which the entire sequence of both the light chain and
the heavy chain, including the CDRs, arise from human genes. Such
antibodies are termed "human antibodies", or "fully human
antibodies" herein. Human monoclonal antibodies can be prepared by
the trioma technique; the human B-cell hybridoma technique (see
Kozbor, et al., 1983 Immunol Today 4: 72) and the EBV hybridoma
technique to produce human monoclonal antibodies (see Cole, et al.,
1985 In: MONOCLONAL ANTIBODIES AND CANCER THERAPY, Alan R. Liss,
Inc., pp. 77-96). Human monoclonal antibodies may be utilized in
the practice of the present invention and may be produced by using
human hybridomas (see Cote, et al., 1983. Proc Natl Acad Sci USA
80: 2026-2030) or by transforming human B-cells with Epstein Barr
Virus in vitro (see Cole, et al., 1985 In: MONOCLONAL ANTIBODIES
AND CANCER THERAPY, Alan R. Liss, Inc., pp. 77-96).
[0143] In addition, human antibodies can also be produced using
additional techniques, including phage display libraries
(Hoogenboom and Winter, J. Mol. Biol., 227:381 (1991); Marks et
al., J. Mol. Biol., 222:581 (1991)). Similarly, human antibodies
can be made by introducing human immunoglobulin loci into
transgenic animals, e.g., mice in which the endogenous
immunoglobulin genes have been partially or completely inactivated.
Upon challenge, human antibody production is observed, which
closely resembles that seen in humans in all respects, including
gene rearrangement, assembly, and antibody repertoire. This
approach is described, for example, in U.S. Pat. Nos. 5,545,807;
5,545,806; 5,569,825; 5,625,126; 5,633,425; 5,661,016, and in Marks
et al. (Bio/Technology 10, 779-783 (1992)); Lonberg et al. (Nature
368 856-859 (1994)); Morrison (Nature 368, 812-13 (1994)); Fishwild
et al, (Nature Biotechnology 14, 845-51 (1996)); Neuberger (Nature
Biotechnology 14, 826 (1996)); and Lonberg and Huszar (Intern. Rev.
Immunol. 13 65-93 (1995)).
[0144] Human antibodies may additionally be produced using
transgenic nonhuman animals which are modified so as to produce
fully human antibodies rather than the animal's endogenous
antibodies in response to challenge by an antigen. (See PCT
publication WO94/02602). The endogenous genes encoding the heavy
and light immunoglobulin chains in the nonhuman host have been
incapacitated, and active loci encoding human heavy and light chain
immunoglobulins are inserted into the host's genome. The human
genes are incorporated, for example, using yeast artificial
chromosomes containing the requisite human DNA segments. An animal
which provides all the desired modifications is then obtained as
progeny by crossbreeding intermediate transgenic animals containing
fewer than the full complement of the modifications. The preferred
embodiment of such a nonhuman animal is a mouse, and is termed the
Xenomouse.TM. as disclosed in PCT publications WO 96/33735 and WO
96/34096. This animal produces B cells which secrete fully human
immunoglobulins. The antibodies can be obtained directly from the
animal after immunization with an immunogen of interest, as, for
example, a preparation of a polyclonal antibody, or alternatively
from immortalized B cells derived from the animal, such as
hybridomas producing monoclonal antibodies. Additionally, the genes
encoding the immunoglobulins with human variable regions can be
recovered and expressed to obtain the antibodies directly, or can
be further modified to obtain analogs of antibodies such as, for
example, single chain Fv molecules.
[0145] An example of a method of producing a nonhuman host,
exemplified as a mouse, lacking expression of an endogenous
immunoglobulin heavy chain is disclosed in U.S. Pat. No. 5,939,598.
It can be obtained by a method including deleting the J segment
genes from at least one endogenous heavy chain locus in an
embryonic stem cell to prevent rearrangement of the locus and to
prevent formation of a transcript of a rearranged immunoglobulin
heavy chain locus, the deletion being effected by a targeting
vector containing a gene encoding a selectable marker; and
producing from the embryonic stem cell a transgenic mouse whose
somatic and germ cells contain the gene encoding the selectable
marker.
[0146] A method for producing an antibody of interest, such as a
human antibody, is disclosed in U.S. Pat. No. 5,916,771. It
includes introducing an expression vector that contains a
nucleotide sequence encoding a heavy chain into one mammalian host
cell in culture, introducing an expression vector containing a
nucleotide sequence encoding a light chain into another mammalian
host cell, and fusing the two cells to form a hybrid cell. The
hybrid cell expresses an antibody containing the heavy chain and
the light chain.
[0147] In a further improvement on this procedure, a method for
identifying a clinically relevant epitope on an immunogen, and a
correlative method for selecting an antibody that binds
immunospecifically to the relevant epitope with high affinity, are
disclosed in PCT publication WO 99/53049.
[0148] F.sub.ab Fragments and Single Chain Antibodies
[0149] According to the invention, techniques can be adapted for
the production of single-chain antibodies specific to an antigenic
protein of the invention (see e.g., U.S. Pat. No. 4,946,778). In
addition, methods can be adapted for the construction of Fab
expression libraries (see e.g., Huse, et al., 1989 Science 246:
1275-1281) to allow rapid and effective identification of
monoclonal Fab fragments with the desired specificity for a protein
or derivatives, fragments, analogs or homologs thereof. Antibody
fragments that contain the idiotypes to a protein antigen may be
produced by techniques known in the art including, but not limited
to: (i) an F.sub.(ab')2 fragment produced by pepsin digestion of an
antibody molecule; (ii) an F.sub.ab fragment generated by reducing
the disulfide bridges of an F.sub.(ab')2 fragment; (iii) an
F.sub.ab fragment generated by the treatment of the antibody
molecule with papain and a reducing agent and (iv) F.sub.v
fragments.
[0150] Bispecific Antibodies
[0151] Bispecific antibodies are monoclonal, preferably human or
humanized, antibodies that have binding specificities for at least
two different antigens. In the present case, one of the binding
specificities is for an antigenic protein of the invention. The
second binding target is any other antigen, and advantageously is a
cell-surface protein or receptor or receptor subunit.
[0152] Methods for making bispecific antibodies are known in the
art. Traditionally, the recombinant production of bispecific
antibodies is based on the co-expression of two immunoglobulin
heavy-chain/light-chain pairs, where the two heavy chains have
different specificities (Milstein and Cuello, Nature, 305:537-539
(1983)). Because of the random assortment of immunoglobulin heavy
and light chains, these hybridomas (quadromas) produce a potential
mixture of ten different antibody molecules, of which only one has
the correct bispecific structure. The purification of the correct
molecule is usually accomplished by affinity chromatography steps.
Similar procedures are disclosed in WO 93/08829, published 13 May
1993, and in Traunecker et al., EMBO J. 10:3655-3659 (1991).
[0153] Antibody variable domains with the desired binding
specificities (antibody-antigen combining sites) can be fused to
immunoglobulin constant domain sequences. The fusion preferably is
with an immunoglobulin heavy-chain constant domain, comprising at
least part of the hinge, CH2, and CH3 regions. It is preferred to
have the first heavy-chain constant region (CH1) containing the
site necessary for light-chain binding present in at least one of
the fusions. DNAs encoding the immunoglobulin heavy-chain fusions
and, if desired, the immunoglobulin light chain, are inserted into
separate expression vectors, and are co-transfected into a suitable
host organism. For further details of generating bispecific
antibodies see, for example, Suresh et al., Methods in Enzymology,
121:210 (1986).
[0154] According to another approach described in WO 96/27011, the
interface between a pair of antibody molecules can be engineered to
maximize the percentage of heterodimers which are recovered from
recombinant cell culture. The preferred interface comprises at
least a part of the CH3 region of an antibody constant domain. In
this method, one or more small amino acid side chains from the
interface of the first antibody molecule are replaced with larger
side chains (e.g. tyrosine or tryptophan). Compensatory "cavities"
of identical or similar size to the large side chain(s) are created
on the interface of the second antibody molecule by replacing large
amino acid side chains with smaller ones (e.g. alanine or
threonine). This provides a mechanism for increasing the yield of
the heterodimer over other unwanted end-products such as
homodimers.
[0155] Bispecific antibodies can be prepared as full length
antibodies or antibody fragments (e.g. F(ab').sub.2 bispecific
antibodies). Techniques for generating bispecific antibodies from
antibody fragments have been described in the literature. For
example, bispecific antibodies can be prepared using chemical
linkage. Brennan et al., Science 229:81 (1985) describe a procedure
wherein intact antibodies are proteolytically cleaved to generate
F(ab').sub.2 fragments. These fragments are reduced in the presence
of the dithiol complexing agent sodium arsenite to stabilize
vicinal dithiols and prevent intermolecular disulfide formation.
The Fab' fragments generated are then converted to
thionitrobenzoate (TNB) derivatives. One of the Fab'-TNB
derivatives is then reconverted to the Fab'-thiol by reduction with
mercaptoethylamine and is mixed with an equimolar amount of the
other Fab'-TNB derivative to form the bispecific antibody. The
bispecific antibodies produced can be used as agents for the
selective immobilization of enzymes.
[0156] Additionally, Fab' fragments can be directly recovered from
E. coli and chemically coupled to form bispecific antibodies.
Shalaby et al., J. Exp. Med. 175:217-225 (1992) describe the
production of a fully humanized bispecific antibody F(ab').sub.2
molecule. Each Fab' fragment was separately secreted from E. coli
and subjected to directed chemical coupling in vitro to form the
bispecific antibody. The bispecific antibody thus formed was able
to bind to cells overexpressing the ErbB2 receptor and normal human
T cells, as well as trigger the lytic activity of human cytotoxic
lymphocytes against human breast tumor targets.
[0157] Various techniques for making and isolating bispecific
antibody fragments directly from recombinant cell culture have also
been described. For example, bispecific antibodies have been
produced using leucine zippers. Kostelny et al., J. Immunol.
148(5):1547-1553 (1992). The leucine zipper peptides from the Fos
and Jun proteins were linked to the Fab' portions of two different
antibodies by gene fusion. The antibody homodimers were reduced at
the hinge region to form monomers and then re-oxidized to form the
antibody heterodimers. This method can also be utilized for the
production of antibody homodimers. The "diabody" technology
described by Hollinger et al., Proc. Natl. Acad. Sci. USA
90:6444-6448 (1993) has provided an alternative mechanism for
making bispecific antibody fragments. The fragments comprise a
heavy-chain variable domain (V.sub.H) connected to a light-chain
variable domain (V.sub.L) by a linker which is too short to allow
pairing between the two domains on the same chain. Accordingly, the
V.sub.H and V.sub.L domains of one fragment are forced to pair with
the complementary V.sub.L and V.sub.H domains of another fragment,
thereby forming two antigen-binding sites. Another strategy for
making bispecific antibody fragments by the use of single-chain Fv
(sFv) dimers has also been reported. See, Gruber et al., J.
Immunol. 152:5368 (1994).
[0158] Antibodies with more than two valencies are contemplated.
For example, trispecific antibodies can be prepared. Tutt et al.,
J. Immunol. 147:60 (1991).
[0159] Exemplary bispecific antibodies can bind to two different
epitopes, at least one of which originates in the protein antigen
of the invention. Alternatively, an anti-antigenic arm of an
immunoglobulin molecule can be combined with an arm which binds to
a triggering molecule on a leukocyte such as a T-cell receptor
molecule (e.g. CD2, CD3, CD28, or B7), or Fc receptors for IgG
(Fc.gamma.R), such as Fc.gamma.RI (CD64), Fc.gamma.RII (CD32) and
Fc.gamma.RIII (CD16) so as to focus cellular defense mechanisms to
the cell expressing the particular antigen. Bispecific antibodies
can also be used to direct cytotoxic agents to cells which express
a particular antigen. These antibodies possess an antigen-binding
arm and an arm which binds a cytotoxic agent or a radionuclide
chelator, such as EOTUBE, DPTA, DOTA, or TETA. Another bispecific
antibody of interest binds the protein antigen described herein and
further binds tissue factor (TF).
[0160] Heteroconjugate Antibodies
[0161] Heteroconjugate antibodies are also within the scope of the
present invention. Heteroconjugate antibodies are composed of two
covalently joined antibodies. Such antibodies have, for example,
been proposed to target immune system cells to unwanted cells (U.S.
Pat. No. 4,676,980), and for treatment of HIV infection (WO
91/00360; WO 92/200373; EP 03089). It is contemplated that the
antibodies can be prepared in vitro using known methods in
synthetic protein chemistry, including those involving crosslinking
agents. For example, immunotoxins can be constructed using a
disulfide exchange reaction or by forming a thioether bond.
Examples of suitable reagents for this purpose include
iminothiolate and methyl-4-mercaptobutyrimidate and those
disclosed, for example, in U.S. Pat. No. 4,676,980.
[0162] Effector Function Engineering
[0163] It can be desirable to modify the antibody of the invention
with respect to effector function, so as to enhance, e.g., the
effectiveness of the antibody in treating cancer. For example,
cysteine residue(s) can be introduced into the Fc region, thereby
allowing interchain disulfide bond formation in this region. The
homodimeric antibody thus generated can have improved
internalization capability and/or increased complement-mediated
cell killing and antibody-dependent cellular cytotoxicity (ADCC).
See Caron et al., J. Exp Med., 176: 1191-1195 (1992) and Shopes, J.
Immunol., 148: 2918-2922 (1992). Homodimeric antibodies with
enhanced anti-tumor activity can also be prepared using
heterobifunctional cross-linkers as described in Wolff et al.
Cancer Research, 53: 2560-2565 (1993). Alternatively, an antibody
can be engineered that has dual Fc regions and can thereby have
enhanced complement lysis and ADCC capabilities. See Stevenson et
al., Anti-Cancer Drug Design. 3: 219-230 (1989).
[0164] Immunoconjugates
[0165] The invention also pertains to immunoconjugates comprising
an antibody conjugated to a cytotoxic agent such as a
chemotherapeutic agent, toxin (e.g., an enzymatically active toxin
of bacterial, fungal, plant, or animal origin, or fragments
thereof), or a radioactive isotope (i.e., a radioconjugate).
[0166] Chemotherapeutic agents useful in the generation of such
immunoconjugates have been described above. Enzymatically active
toxins and fragments thereof that can be used include diphtheria A
chain, nonbinding active fragments of diphtheria toxin, exotoxin A
chain (from Pseudomonas aeruginosa), ricin A chain, abrin A chain,
modeccin A chain, alpha-sarcin, Aleurites fordii proteins, dianthin
proteins, Phytolaca americana proteins (PAPI, PAPII, and PAP-S),
momordica charantia inhibitor, curcin, crotin, sapaonaria
officinalis inhibitor, gelonin, mitogellin, restrictocin,
phenomycin, enomycin, and the tricothecenes. A variety of
radionuclides are available for the production of radioconjugated
antibodies. Examples include .sup.212Bi, .sup.131I, .sup.131In,
.sup.90Y, and .sup.186Re.
[0167] Conjugates of the antibody and cytotoxic agent are made
using a variety of bifunctional protein-coupling agents such as
N-succinimidyl-3-(2-pyridyldithiol) propionate (SPDP),
iminothiolane (IT), bifunctional derivatives of imidoesters (such
as dimethyl adipimidate HCL), active esters (such as disuccinimidyl
suberate), aldehydes (such as glutareldehyde), bis-azido compounds
(such as bis (p-azidobenzoyl) hexanediamine), bis-diazonium
derivatives (such as bis-(p-diazoniumbenzoyl)-ethylenediamine),
diisocyanates (such as tolyene 2,6-diisocyanate), and bis-active
fluorine compounds (such as 1,5-difluoro-2,4-dinitrobenzene). For
example, a ricin immunotoxin can be prepared as described in
Vitetta et al., Science, 238: 1098 (1987). Carbon-14-labeled
1-isothiocyanatobenzyl-3-methyldiethylene triaminepentaacetic acid
(MX-DTPA) is an exemplary chelating agent for conjugation of
radionucleotide to the antibody. See WO94/11026.
[0168] In another embodiment, the antibody can be conjugated to a
"receptor" (such streptavidin) for utilization in tumor
pretargeting wherein the antibody-receptor conjugate is
administered to the patient, followed by removal of unbound
conjugate from the circulation using a clearing agent and then
administration of a "ligand" (e.g., avidin) that is in turn
conjugated to a cytotoxic agent.
[0169] Immunoliposomes
[0170] The antibodies disclosed herein can also be formulated as
immunoliposomes. Liposomes containing the antibody are prepared by
methods known in the art, such as described in Epstein et al.,
Proc. Natl. Acad. Sci. USA, 82: 3688 (1985); Hwang et al., Proc.
Natl. Acad. Sci. USA, 77: 4030 (1980); and U.S. Pat. Nos. 4,485,045
and 4,544,545. Liposomes with enhanced circulation time are
disclosed in U.S. Pat. No. 5,013,556.
[0171] Particularly useful liposomes can be generated by the
reverse-phase evaporation method with a lipid composition
comprising phosphatidylcholine, cholesterol, and PEG-derivatized
phosphatidylethanolamine (PEG-PE). Liposomes are extruded through
filters of defined pore size to yield liposomes with the desired
diameter. Fab' fragments of the antibody of the present invention
can be conjugated to the liposomes as described in Martin et al.,
J. Biol. Chem., 257: 286-288 (1982) via a disulfide-interchange
reaction. A chemotherapeutic agent (such as Doxorubicin) is
optionally contained within the liposome. See Gabizon et al., J.
National Cancer Inst., 81(19): 1484 (1989).
Diagnostic Applications of Antibodies Directed Against the Proteins
of the Invention
[0172] Antibodies directed against a protein of the invention may
be used in methods known within the art relating to the
localization and/or quantitation of the protein (e.g., for use in
measuring levels of the protein within appropriate physiological
samples, for use in diagnostic methods, for use in imaging the
protein, and the like). In a given embodiment, antibodies against
the proteins, or derivatives, fragments, analogs or homologs
thereof, that contain the antigen binding domain, are utilized as
pharmacologically-active compounds (see below).
[0173] An antibody specific for a protein of the invention can be
used to isolate the protein by standard techniques, such as
immunoaffinity chromatography or immunoprecipitation. Such an
antibody can facilitate the purification of the natural protein
antigen from cells and of recombinantly produced antigen expressed
in host cells. Moreover, such an antibody can be used to detect the
antigenic protein (e.g., in a cellular lysate or cell supernatant)
in order to evaluate the abundance and pattern of expression of the
antigenic protein. Antibodies directed against the protein can be
used diagnostically to monitor protein levels in tissue as part of
a clinical testing procedure, e.g., to, for example, determine the
efficacy of a given treatment regimen. Detection can be facilitated
by coupling (i.e., physically linking) the antibody to a detectable
substance. Examples of detectable substances include various
enzymes, prosthetic groups, fluorescent materials, luminescent
materials, bioluminescent materials, and radioactive materials.
Examples of suitable enzymes include horseradish peroxidase,
alkaline phosphatase, .beta.-galactosidase, or
acetylcholinesterase; examples of suitable prosthetic group
complexes include streptavidin/biotin and avidin/biotin; examples
of suitable fluorescent materials include umbelliferone,
fluorescein, fluorescein isothiocyanate, rhodamine,
dichlorotriazinylamine fluorescein, dansyl chloride or
phycoerythrin; an example of a luminescent material includes
luminol; examples of bioluminescent materials include luciferase,
luciferin, and aequorin, and examples of suitable radioactive
material include .sup.125I, .sup.131I, .sup.35S or .sup.3H.
[0174] Antibody Therapeutics
[0175] Antibodies of the invention, including polyclonal,
monoclonal, humanized and fully human antibodies, may used as
therapeutic agents. Such agents will generally be employed to treat
or prevent a disease or pathology in a subject. An antibody
preparation, preferably one having high specificity and high
affinity for its target antigen, is administered to the subject and
will generally have an effect due to its binding with the target.
Such an effect may be one of two kinds, depending on the specific
nature of the interaction between the given antibody molecule and
the target antigen in question. In the first instance,
administration of the antibody may abrogate or inhibit the binding
of the target with an endogenous ligand to which it naturally
binds. In this case, the antibody binds to the target and masks a
binding site of the naturally occurring ligand, wherein the ligand
serves as an effector molecule. Thus the receptor mediates a signal
transduction pathway for which ligand is responsible.
[0176] Alternatively, the effect may be one in which the antibody
elicits a physiological result by virtue of binding to an effector
binding site on the target molecule. In this case the target, a
receptor having an endogenous ligand which may be absent or
defective in the disease or pathology, binds the antibody as a
surrogate effector ligand, initiating a receptor-based signal
transduction event by the receptor.
[0177] A therapeutically effective amount of an antibody of the
invention relates generally to the amount needed to achieve a
therapeutic objective. As noted above, this may be a binding
interaction between the antibody and its target antigen that, in
certain cases, interferes with the functioning of the target, and
in other cases, promotes a physiological response. The amount
required to be administered will furthermore depend on the binding
affinity of the antibody for its specific antigen, and will also
depend on the rate at which an administered antibody is depleted
from the free volume other subject to which it is administered.
Common ranges for therapeutically effective dosing of an antibody
or antibody fragment of the invention may be, by way of nonlimiting
example, from about 0.1 mg/kg body weight to about 50 mg/kg body
weight. Common dosing frequencies may range, for example, from
twice daily to once a week.
[0178] Pharmaceutical Compositions of Antibodies
[0179] Antibodies specifically binding a protein of the invention,
as well as other molecules identified by the screening assays
disclosed herein, can be administered for the treatment of various
disorders in the form of pharmaceutical compositions. Principles
and considerations involved in preparing such compositions, as well
as guidance in the choice of components are provided, for example,
in Remington: The Science And Practice Of Pharmacy 19th ed.
(Alfonso R. Gennaro, et al., editors) Mack Pub. Co., Easton, Pa.:
1995; Drug Absorption Enhancement: Concepts, Possibilities,
Limitations, And Trends, Harwood Academic Publishers, Langhorne,
Pa., 1994; and Peptide And Protein Drug Delivery (Advances In
Parenteral Sciences, Vol. 4), 1991, M. Dekker, New York.
[0180] If the antigenic protein is intracellular and whole
antibodies are used as inhibitors, internalizing antibodies are
preferred. However, liposomes can also be used to deliver the
antibody, or an antibody fragment, into cells. Where antibody
fragments are used, the smallest inhibitory fragment that
specifically binds to the binding domain of the target protein is
preferred. For example, based upon the variable-region sequences of
an antibody, peptide molecules can be designed that retain the
ability to bind the target protein sequence. Such peptides can be
synthesized chemically and/or produced by recombinant DNA
technology. See, e.g., Marasco et al., Proc. Natl. Acad. Sci. USA,
90: 7889-7893 (1993). The formulation herein can also contain more
than one active compound as necessary for the particular indication
being treated, preferably those with complementary activities that
do not adversely affect each other. Alternatively, or in addition,
the composition can comprise an agent that enhances its function,
such as, for example, a cytotoxic agent, cytokine, chemotherapeutic
agent, or growth-inhibitory agent. Such molecules are suitably
present in combination in amounts that are effective for the
purpose intended.
[0181] The active ingredients can also be entrapped in
microcapsules prepared, for example, by coacervation techniques or
by interfacial polymerization, for example, hydroxymethylcellulose
or gelatin-microcapsules and poly-(methylmethacrylate)
microcapsules, respectively, in colloidal drug delivery systems
(for example, liposomes, albumin microspheres, microemulsions,
nano-particles, and nanocapsules) or in macroemulsions.
[0182] The formulations to be used for in vivo administration must
be sterile. This is readily accomplished by filtration through
sterile filtration membranes.
[0183] Sustained-release preparations can be prepared. Suitable
examples of sustained-release preparations include semipermeable
matrices of solid hydrophobic polymers containing the antibody,
which matrices are in the form of shaped articles, e.g., films, or
microcapsules. Examples of sustained-release matrices include
polyesters, hydrogels (for example,
poly(2-hydroxyethyl-methacrylate), or poly(vinylalcohol)),
polylactides (U.S. Pat. No. 3,773,919), copolymers of L-glutamic
acid and .gamma. ethyl-L-glutamate, non-degradable ethylene-vinyl
acetate, degradable lactic acid-glycolic acid copolymers such as
the LUPRON DEPOT.TM. (injectable microspheres composed of lactic
acid-glycolic acid copolymer and leuprolide acetate), and
poly-D-(-)-3-hydroxybutyric acid. While polymers such as
ethylene-vinyl acetate and lactic acid-glycolic acid enable release
of molecules for over 100 days, certain hydrogels release proteins
for shorter time periods.
[0184] ELISA Assay
[0185] An agent for detecting an analyte protein is an antibody
capable of binding to an analyte protein, preferably an antibody
with a detectable label. Antibodies can be polyclonal, or more
preferably, monoclonal. An intact antibody, or a fragment thereof
(e.g., F.sub.ab or F.sub.(ab)2) can be used. The term "labeled",
with regard to the probe or antibody, is intended to encompass
direct labeling of the probe or antibody by coupling (i.e.,
physically linking) a detectable substance to the probe or
antibody, as well as indirect labeling of the probe or antibody by
reactivity with another reagent that is directly labeled. Examples
of indirect labeling include detection of a primary antibody using
a fluorescently-labeled secondary antibody and end-labeling of a
DNA probe with biotin such that it can be detected with
fluorescently-labeled streptavidin. The term "biological sample" is
intended to include tissues, cells and biological fluids isolated
from a subject, as well as tissues, cells and fluids present within
a subject. Included within the usage of the term "biological
sample", therefore, is blood and a fraction or component of blood
including blood serum, blood plasma, or lymph. That is, the
detection method of the invention can be used to detect an analyte
mRNA, protein, or genomic DNA in a biological sample in vitro as
well as in vivo. For example, in vitro techniques for detection of
an analyte mRNA include Northern hybridizations and in situ
hybridizations. In vitro techniques for detection of an analyte
protein include enzyme linked immunosorbent assays (ELISAs),
Western blots, immunoprecipitations, and immunofluorescence. In
vitro techniques for detection of an analyte genomic DNA include
Southern hybridizations. Procedures for conducting immunoassays are
described, for example in "ELISA: Theory and Practice: Methods in
Molecular Biology", Vol. 42, J. R. Crowther (Ed.) Human Press,
Totowa, N.J., 1995; "Immunoassay", E. Diamandis and T.
Christopoulus, Academic Press, Inc., San Diego, Calif., 1996; and
"Practice and Thory of Enzyme Immunoassays", P. Tijssen, Elsevier
Science Publishers, Amsterdam, 1985. Furthermore, in vivo
techniques for detection of an analyte protein include introducing
into a subject a labeled anti-an analyte protein antibody. For
example, the antibody can be labeled with a radioactive marker
whose presence and location in a subject can be detected by
standard imaging techniques.
[0186] NOVX Recombinant Expression Vectors and Host Cells
[0187] Another aspect of the invention pertains to vectors,
preferably expression vectors, containing a nucleic acid encoding A
NOVX protein, or derivatives, fragments, analogs or homologs
thereof. As used herein, the term "vector" refers to a nucleic acid
molecule capable of transporting another nucleic acid to which it
has been linked. One type of vector is a "plasmid", which refers to
a circular double stranded DNA loop into which additional DNA
segments can be ligated. Another type of vector is a viral vector,
wherein additional DNA segments can be ligated into the viral
genome. Certain vectors are capable of autonomous replication in a
host cell into which they are introduced (e.g., bacterial vectors
having a bacterial origin of replication and episomal mammalian
vectors). Other vectors (e.g., non-episomal mammalian vectors) are
integrated into the genome of a host cell upon introduction into
the host cell, and thereby are replicated along with the host
genome. Moreover, certain vectors are capable of directing the
expression of genes to which they are operatively-linked. Such
vectors are referred to herein as "expression vectors". In general,
expression vectors of utility in recombinant DNA techniques are
often in the form of plasmids. In the present specification,
"plasmid" and "vector" can be used interchangeably as the plasmid
is the most commonly used form of vector. However, the invention is
intended to include such other forms of expression vectors, such as
viral vectors (e.g., replication defective retroviruses,
adenoviruses and adeno-associated viruses), which serve equivalent
functions.
[0188] The recombinant expression vectors of the invention comprise
a nucleic acid of the invention in a form suitable for expression
of the nucleic acid in a host cell, which means that the
recombinant expression vectors include one or more regulatory
sequences, selected on the basis of the host cells to be used for
expression, that is operatively-linked to the nucleic acid sequence
to be expressed. Within a recombinant expression vector,
"operably-linked" is intended to mean that the nucleotide sequence
of interest is linked to the regulatory sequence(s) in a manner
that allows for expression of the nucleotide sequence (e.g., in an
in vitro transcription/translation system or in a host cell when
the vector is introduced into the host cell).
[0189] The term "regulatory sequence" is intended to includes
promoters, enhancers and other expression control elements (e.g.,
polyadenylation signals). Such regulatory sequences are described,
for example, in Goeddel, GENE EXPRESSION TECHNOLOGY: METHODS IN
ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990).
Regulatory sequences include those that direct constitutive
expression of a nucleotide sequence in many types of host cell and
those that direct expression of the nucleotide sequence only in
certain host cells (e.g., tissue-specific regulatory sequences). It
will be appreciated by those skilled in the art that the design of
the expression vector can depend on such factors as the choice of
the host cell to be transformed, the level of expression of protein
desired, etc. The expression vectors of the invention can be
introduced into host cells to thereby produce proteins or peptides,
including fusion proteins or peptides, encoded by nucleic acids as
described herein (e.g., NOVX proteins, mutant forms of NOVX
proteins, fusion proteins, etc.).
[0190] The recombinant expression vectors of the invention can be
designed for expression of NOVX proteins in prokaryotic or
eukaryotic cells. For example, NOVX proteins can be expressed in
bacterial cells such as Escherichia coli, insect cells (using
baculovirus expression vectors) yeast cells or mammalian cells.
Suitable host cells are discussed further in Goeddel, GENE
EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press,
San Diego, Calif. (1990). Alternatively, the recombinant expression
vector can be transcribed and translated in vitro, for example
using T7 promoter regulatory sequences and T7 polymerase.
[0191] Expression of proteins in prokaryotes is most often carried
out in Escherichia coli with vectors containing constitutive or
inducible promoters directing the expression of either fusion or
non-fusion proteins. Fusion vectors add a number of amino acids to
a protein encoded therein, usually to the amino terminus of the
recombinant protein. Such fusion vectors typically serve three
purposes: (i) to increase expression of recombinant protein; (ii)
to increase the solubility of the recombinant protein; and (iii) to
aid in the purification of the recombinant protein by acting as a
ligand in affinity purification. Often, in fusion expression
vectors, a proteolytic cleavage site is introduced at the junction
of the fusion moiety and the recombinant protein to enable
separation of the recombinant protein from the fusion moiety
subsequent to purification of the fusion protein. Such enzymes, and
their cognate recognition sequences, include Factor Xa, thrombin
and enterokinase. Typical fusion expression vectors include pGEX
(Pharmacia Biotech Inc; Smith and Johnson, 1988. Gene 67: 31-40),
pMAL (New England Biolabs, Beverly, Mass.) and pRIT5 (Pharmacia,
Piscataway, N.J.) that fuse glutathione S-transferase (GST),
maltose E binding protein, or protein A, respectively, to the
target recombinant protein.
[0192] Examples of suitable inducible non-fusion E. coli expression
vectors include pTrc (Amrann et al., (1988) Gene 69:301-315) and
pET 11d (Studier et al., GENE EXPRESSION TECHNOLOGY: METHODS IN
ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990)
60-89).
[0193] One strategy to maximize recombinant protein expression in
E. coli is to express the protein in a host bacteria with an
impaired capacity to proteolytically cleave the recombinant
protein. See, e.g., Gottesman, GENE EXPRESSION TECHNOLOGY: METHODS
IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990)
119-128. Another strategy is to alter the nucleic acid sequence of
the nucleic acid to be inserted into an expression vector so that
the individual codons for each amino acid are those preferentially
utilized in E. coli (see, e.g., Wada, et al., 1992. Nucl. Acids
Res. 20: 2111-2118). Such alteration of nucleic acid sequences of
the invention can be carried out by standard DNA synthesis
techniques.
[0194] In another embodiment, the NOVX expression vector is a yeast
expression vector. Examples of vectors for expression in yeast
Saccharomyces cerivisae include pYepSec1 (Baldari, et al., 1987.
EMBO J. 6: 229-234), pMFa (Kuijan and Herskowitz, 1982. Cell 30:
933-943), pJRY88 (Schultz et al., 1987. Gene 54: 113-123), pYES2
(Invitrogen Corporation, San Diego, Calif.), and picZ (InVitrogen
Corp, San Diego, Calif.).
[0195] Alternatively, NOVX can be expressed in insect cells using
baculovirus expression vectors. Baculovirus vectors available for
expression of proteins in cultured insect cells (e.g., SF9 cells)
include the pAc series (Smith, et al., 1983. Mol. Cell. Biol. 3:
2156-2165) and the pVL series (Lucklow and Summers, 1989. Virology
170: 31-39).
[0196] In yet another embodiment, a nucleic acid of the invention
is expressed in mammalian cells using a mammalian expression
vector. Examples of mammalian expression vectors include pCDM8
(Seed, 1987. Nature 329: 840) and pMT2PC (Kaufinan, et al., 1987.
EMBO J. 6:187-195). When used in mammalian cells, the expression
vector's control functions are often provided by viral regulatory
elements. For example, commonly used promoters are derived from
polyoma, adenovirus 2, cytomegalovirus, and simian virus 40. For
other suitable expression systems for both prokaryotic and
eukaryotic cells see, e.g., Chapters 16 and 17 of Sambrook, et al.,
MOLECULAR CLONING: A LABORATORY MANUAL. 2nd ed., Cold Spring Harbor
Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring
Harbor, N.Y., 1989.
[0197] In another embodiment, the recombinant mammalian expression
vector is capable of directing expression of the nucleic acid
preferentially in a particular cell type (e.g., tissue-specific
regulatory elements are used to express the nucleic acid).
Tissue-specific regulatory elements are known in the art.
Non-limiting examples of suitable tissue-specific promoters include
the albumin promoter (liver-specific; Pinkert, et al., 1987. Genes
Dev. 1: 268-277), lymphoid-specific promoters (Calame and Eaton,
1988. Adv. Immunol. 43: 235-275), in particular promoters of T cell
receptors (Winoto and Baltimore, 1989. EMBO J. 8: 729-733) and
immunoglobulins (Baneiji, et al., 1983. Cell 33: 729-740; Queen and
Baltimore, 1983. Cell 33: 741-748), neuron-specific promoters
(e.g., the neurofilament promoter; Byrne and Ruddle, 1989. Proc.
Natl. Acad. Sci. USA 86: 5473-5477), pancreas-specific promoters
(Edlund, et al., 1985. Science 230: 912-916), and mammary
gland-specific promoters (e.g., milk whey promoter; U.S. Pat. No.
4,873,316 and European Application Publication No. 264,166).
Developmentally-regulated promoters are also encompassed, e.g., the
murine hox promoters (Kessel and Gruss, 1990. Science 249: 374-379)
and the .alpha.-fetoprotein promoter (Campes and Tilghman, 1989.
Genes Dev. 3: 537-546).
[0198] The invention further provides a recombinant expression
vector comprising a DNA molecule of the invention cloned into the
expression vector in an antisense orientation. That is, the DNA
molecule is operatively-linked to a regulatory sequence in a manner
that allows for expression (by transcription of the DNA molecule)
of an RNA molecule that is antisense to NOVX mRNA. Regulatory
sequences operatively linked to a nucleic acid cloned in the
antisense orientation can be chosen that direct the continuous
expression of the antisense RNA molecule in a variety of cell
types, for instance viral promoters and/or enhancers, or regulatory
sequences can be chosen that direct constitutive, tissue specific
or cell type specific expression of antisense RNA. The antisense
expression vector can be in the form of a recombinant plasmid,
phagemid or attenuated virus in which antisense nucleic acids are
produced under the control of a high efficiency regulatory region,
the activity of which can be determined by the cell type into which
the vector is introduced. For a discussion of the regulation of
gene expression using antisense genes see, e.g., Weintraub, et al.,
"Antisense RNA as a molecular tool for genetic analysis,"
Reviews-Trends in Genetics, Vol. 1(1) 1986.
[0199] Another aspect of the invention pertains to host cells into
which a recombinant expression vector of the invention has been
introduced. The terms "host cell" and "recombinant host cell" are
used interchangeably herein. It is understood that such terms refer
not only to the particular subject cell but also to the progeny or
potential progeny of such a cell. Because certain modifications may
occur in succeeding generations due to either mutation or
environmental influences, such progeny may not, in fact, be
identical to the parent cell, but are still included within the
scope of the term as used herein.
[0200] A host cell can be any prokaryotic or eukaryotic cell. For
example, NOVX protein can be expressed in bacterial cells such as
E. coli, insect cells, yeast or mammalian cells (such as Chinese
hamster ovary cells (CHO) or COS cells). Other suitable host cells
are known to those skilled in the art.
[0201] Vector DNA can be introduced into prokaryotic or eukaryotic
cells via conventional transformation or transfection techniques.
As used herein, the terms "transformation" and "transfection" are
intended to refer to a variety of art-recognized techniques for
introducing foreign nucleic acid (e.g., DNA) into a host cell,
including calcium phosphate or calcium chloride co-precipitation,
DEAE-dextran-mediated transfection, lipofection, or
electroporation. Suitable methods for transforming or transfecting
host cells can be found in Sambrook, et al. (MOLECULAR CLONING: A
LABORATORY MANUAL. 2nd ed., Cold Spring Harbor Laboratory, Cold
Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989),
and other laboratory manuals.
[0202] For stable transfection of mammalian cells, it is known
that, depending upon the expression vector and transfection
technique used, only a small fraction of cells may integrate the
foreign DNA into their genome. In order to identify and select
these integrants, a gene that encodes a selectable marker (e.g.,
resistance to antibiotics) is generally introduced into the host
cells along with the gene of interest. Various selectable markers
include those that confer resistance to drugs, such as G418,
hygromycin and methotrexate. Nucleic acid encoding a selectable
marker can be introduced into a host cell on the same vector as
that encoding NOVX or can be introduced on a separate vector. Cells
stably transfected with the introduced nucleic acid can be
identified by drug selection (e.g., cells that have incorporated
the selectable marker gene will survive, while the other cells
die).
[0203] A host cell of the invention, such as a prokaryotic or
eukaryotic host cell in culture, can be used to produce (i.e.,
express) NOVX protein. Accordingly, the invention further provides
methods for producing NOVX protein using the host cells of the
invention. In one embodiment, the method comprises culturing the
host cell of invention (into which a recombinant expression vector
encoding NOVX protein has been introduced) in a suitable medium
such that NOVX protein is produced. In another embodiment, the
method further comprises isolating NOVX protein from the medium or
the host cell.
[0204] Transgenic NOVX Animals
[0205] The host cells of the invention can also be used to produce
non-human transgenic animals. For example, in one embodiment, a
host cell of the invention is a fertilized oocyte or an embryonic
stem cell into which NOVX protein-coding sequences have been
introduced. Such host cells can then be used to create non-human
transgenic animals in which exogenous NOVX sequences have been
introduced into their genome or homologous recombinant animals in
which endogenous NOVX sequences have been altered. Such animals are
useful for studying the function and/or activity of NOVX protein
and for identifying and/or evaluating modulators of NOVX protein
activity. As used herein, a "transgenic animal" is a non-human
animal, preferably a mammal, more preferably a rodent such as a rat
or mouse, in which one or more of the cells of the animal includes
a transgene. Other examples of transgenic animals include non-human
primates, sheep, dogs, cows, goats, chickens, amphibians, etc. A
transgene is exogenous DNA that is integrated into the genome of a
cell from which a transgenic animal develops and that remains in
the genome of the mature animal, thereby directing the expression
of an encoded gene product in one or more cell types or tissues of
the transgenic animal. As used herein, a "homologous recombinant
animal" is a non-human animal, preferably a mammal, more preferably
a mouse, in which an endogenous NOVX gene has been altered by
homologous recombination between the endogenous gene and an
exogenous DNA molecule introduced into a cell of the animal, e.g.,
an embryonic cell of the animal, prior to development of the
animal.
[0206] A transgenic animal of the invention can be created by
introducing NOVX-encoding nucleic acid into the male pronuclei of a
fertilized oocyte (e.g., by microinjection, retroviral infection)
and allowing the oocyte to develop in a pseudopregnant female
foster animal. The human NOVX cDNA sequences SEQ ID NOS:2n-1,
wherein n is an integer between 1 and 54, can be introduced as a
transgene into the genome of a non-human animal. Alternatively, a
non-human homologue of the human NOVX gene, such as a mouse NOVX
gene, can be isolated based on hybridization to the human NOVX cDNA
(described further supra) and used as a transgene. Intronic
sequences and polyadenylation signals can also be included in the
transgene to increase the efficiency of expression of the
transgene. A tissue-specific regulatory sequence(s) can be
operably-linked to the NOVX transgene to direct expression of NOVX
protein to particular cells. Methods for generating transgenic
animals via embryo manipulation and microinjection, particularly
animals such as mice, have become conventional in the art and are
described, for example, in U.S. Pat. Nos. 4,736,866; 4,870,009; and
4,873,191; and Hogan, 1986. In: MANIPULATING THE MOUSE EMBRYO, Cold
Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. Similar
methods are used for production of other transgenic animals. A
transgenic founder animal can be identified based upon the presence
of the NOVX transgene in its genome and/or expression of NOVX mRNA
in tissues or cells of the animals. A transgenic founder animal can
then be used to breed additional animals carrying the transgene.
Moreover, transgenic animals carrying a transgene-encoding NOVX
protein can further be bred to other transgenic animals carrying
other transgenes.
[0207] To create a homologous recombinant animal, a vector is
prepared which contains at least a portion of A NOVX gene into
which a deletion, addition or substitution has been introduced to
thereby alter, e.g., functionally disrupt, the NOVX gene. The NOVX
gene can be a human gene (e.g., the cDNA of SEQ ID NOS:2n-1,
wherein n is an integer between 1 and 54), but more preferably, is
a non-human homologue of a human NOVX gene. For example, a mouse
homologue of human NOVX gene of SEQ ID NOS:2n-1, wherein n is an
integer between 1 and 54, can be used to construct a homologous
recombination vector suitable for altering an endogenous NOVX gene
in the mouse genome. In one embodiment, the vector is designed such
that, upon homologous recombination, the endogenous NOVX gene is
functionally disrupted (i.e., no longer encodes a functional
protein; also referred to as a "knock out" vector).
[0208] Alternatively, the vector can be designed such that, upon
homologous recombination, the endogenous NOVX gene is mutated or
otherwise altered but still encodes functional protein (e.g., the
upstream regulatory region can be altered to thereby alter the
expression of the endogenous NOVX protein). In the homologous
recombination vector, the altered portion of the NOVX gene is
flanked at its 5'- and 3'-termini by additional nucleic acid of the
NOVX gene to allow for homologous recombination to occur between
the exogenous NOVX gene carried by the vector and an endogenous
NOVX gene in an embryonic stem cell. The additional flanking NOVX
nucleic acid is of sufficient length for successful homologous
recombination with the endogenous gene. Typically, several
kilobases of flanking DNA (both at the 5'- and 3'-termini) are
included in the vector. See, e.g., Thomas, et al., 1987. Cell 51:
503 for a description of homologous recombination vectors. The
vector is ten introduced into an embryonic stem cell line (e.g., by
electroporation) and cells in which the introduced NOVX gene has
homologously-recombined with the endogenous NOVX gene are selected.
See, e.g., Li, et al., 1992. Cell 69:915.
[0209] The selected cells are then injected into a blastocyst of an
animal (e.g., a mouse) to form aggregation chimeras. See, e.g.,
Bradley, 1987. In: TERATOCARCINOMAS AND EMBRYONIC STEM CELLS: A
PRACTICAL APPROACH, Robertson, ed. IRL, Oxford, pp. 113-152. A
chimeric embryo can then be implanted into a suitable
pseudopregnant female foster animal and the embryo brought to term.
Progeny harboring the homologously-recombined DNA in their germ
cells can be used to breed animals in which all cells of the animal
contain the homologously-recombined DNA by germline transmission of
the transgene. Methods for constructing homologous recombination
vectors and homologous recombinant animals are described further in
Bradley, 1991. Curr. Opin. Biotechnol. 2: 823-829; PCT
International Publication Nos.: WO 90/11354; WO 91/01140; WO
92/0968; and WO 93/04169.
[0210] In another embodiment, transgenic non-humans animals can be
produced that contain selected systems that allow for regulated
expression of the transgene. One example of such a system is the
cre/loxP recombinase system of bacteriophage P1. For a description
of the cre/loxP recombinase system, See, e.g., Lakso, et al., 1992.
Proc. Natl. Acad. Sci. USA 89: 6232-6236. Another example of a
recombinase system is the FLP recombinase system of Saccharomyces
cerevisiae. See, O'Gorman, et al., 1991. Science 251:1351-1355. If
a cre/loxP recombinase system is used to regulate expression of the
transgene, animals containing transgenes encoding both the Cre
recombinase and a selected protein are required. Such animals can
be provided through the construction of "double" transgenic
animals, e.g., by mating two transgenic animals, one containing a
transgene encoding a selected protein and the other containing a
transgene encoding a recombinase.
[0211] Clones of the non-human transgenic animals described herein
can also be produced according to the methods described in Wilmnut,
et al., 1997. Nature 385: 810-813. In brief, a cell (e.g., a
somatic cell) from the transgenic animal can be isolated and
induced to exit the growth cycle and enter G.sub.0 phase. The
quiescent cell can then be fused, e.g., through the use of
electrical pulses, to an enucleated oocyte from an animal of the
same species from which the quiescent cell is isolated. The
reconstructed oocyte is then cultured such that it develops to
morula or blastocyte and then transferred to pseudopregnant female
foster animal. The offspring borne of this female foster animal
will be a clone of the animal from which the cell (e.g., the
somatic cell) is isolated.
[0212] Pharmaceutical Compositions
[0213] The NOVX nucleic acid molecules, NOVX proteins, and
anti-NOVX antibodies (also referred to herein as "active
compounds") of the invention, and derivatives, fragments, analogs
and homologs thereof, can be incorporated into pharmaceutical
compositions suitable for administration. Such compositions
typically comprise the nucleic acid molecule, protein, or antibody
and a pharmaceutically acceptable carrier. As used herein,
"pharmaceutically acceptable carrier" is intended to include any
and all solvents, dispersion media, coatings, antibacterial and
antifungal agents, isotonic and absorption delaying agents, and the
like, compatible with pharmaceutical administration. Suitable
carriers are described in the most recent edition of Remington's
Pharmaceutical Sciences, a standard reference text in the field,
which is incorporated herein by reference. Preferred examples of
such carriers or diluents include, but are not limited to, water,
saline, finger's solutions, dextrose solution, and 5% human serum
albumin. Liposomes and non-aqueous vehicles such as fixed oils may
also be used. The use of such media and agents for pharmaceutically
active substances is well known in the art. Except insofar as any
conventional media or agent is incompatible with the active
compound, use thereof in the compositions is contemplated.
Supplementary active compounds can also be incorporated into the
compositions.
[0214] A pharmaceutical composition of the invention is formulated
to be compatible with its intended route of administration.
Examples of routes of administration include parenteral, e.g.,
intravenous, intradermal, subcutaneous, oral (e.g., inhalation),
transdermal (i.e., topical), transmucosal, and rectal
administration. Solutions or suspensions used for parenteral,
intradermal, or subcutaneous application can include the following
components: a sterile diluent such as water for injection, saline
solution, fixed oils, polyethylene glycols, glycerine, propylene
glycol or other synthetic solvents; antibacterial agents such as
benzyl alcohol or methyl parabens; antioxidants such as ascorbic
acid or sodium bisulfite; chelating agents such as
ethylenediaminetetraacetic acid (EDTA); buffers such as acetates,
citrates or phosphates, and agents for the adjustment of tonicity
such as sodium chloride or dextrose. The pH can be adjusted with
acids or bases, such as hydrochloric acid or sodium hydroxide. The
parenteral preparation can be enclosed in ampoules, disposable
syringes or multiple dose vials made of glass or plastic.
[0215] Pharmaceutical compositions suitable for injectable use
include sterile aqueous solutions (where water soluble) or
dispersions and sterile powders for the extemporaneous preparation
of sterile injectable solutions or dispersion. For intravenous
administration, suitable carriers include physiological saline,
bacteriostatic water, Cremophor EL.TM.(BASF, Parsippany, N.J.) or
phosphate buffered saline (PBS). In all cases, the composition must
be sterile and should be fluid to the extent that easy
syringeability exists. It must be stable under the conditions of
manufacture and storage and must be preserved against the
contaminating action of microorganisms such as bacteria and fungi.
The carrier can be a solvent or dispersion medium containing, for
example, water, ethanol, polyol (for example, glycerol, propylene
glycol, and liquid polyethylene glycol, and the like), and suitable
mixtures thereof. The proper fluidity can be maintained, for
example, by the use of a coating such as lecithin, by the
maintenance of the required particle size in the case of dispersion
and by the use of surfactants. Prevention of the action of
microorganisms can be achieved by various antibacterial and
antifungal agents, for example, parabens, chlorobutanol, phenol,
ascorbic acid, thimerosal, and the like. In many cases, it will be
preferable to include isotonic agents, for example, sugars,
polyalcohols such as manitol, sorbitol, sodium chloride in the
composition. Prolonged absorption of the injectable compositions
can be brought about by including in the composition an agent which
delays absorption, for example, aluminum monostearate and
gelatin.
[0216] Sterile injectable solutions can be prepared by
incorporating the active compound (e.g., A NOVX protein or
anti-NOVX antibody) in the required amount in an appropriate
solvent with one or a combination of ingredients enumerated above,
as required, followed by filtered sterilization. Generally,
dispersions are prepared by incorporating the active compound into
a sterile vehicle that contains a basic dispersion medium and the
required other ingredients from those enumerated above. In the case
of sterile powders for the preparation of sterile injectable
solutions, methods of preparation are vacuum drying and
freeze-drying that yields a powder of the active ingredient plus
any additional desired ingredient from a previously
sterile-filtered solution thereof.
[0217] Oral compositions generally include an inert diluent or an
edible carrier. They can be enclosed in gelatin capsules or
compressed into tablets. For the purpose of oral therapeutic
administration, the active compound can be incorporated with
excipients and used in the form of tablets, troches, or capsules.
Oral compositions can also be prepared using a fluid carrier for
use as a mouthwash, wherein the compound in the fluid carrier is
applied orally and swished and expectorated or swallowed.
Pharmaceutically compatible binding agents, and/or adjuvant
materials can be included as part of the composition. The tablets,
pills, capsules, troches and the like can contain any of the
following ingredients, or compounds of a similar nature: a binder
such as microcrystalline cellulose, gum tragacanth or gelatin; an
excipient such as starch or lactose, a disintegrating agent such as
alginic acid, Primogel, or corn starch; a lubricant such as
magnesium stearate or Sterotes; a glidant such as colloidal silicon
dioxide; a sweetening agent such as sucrose or saccharin; or a
flavoring agent such as peppermint, methyl salicylate, or orange
flavoring.
[0218] For administration by inhalation, the compounds are
delivered in the form of an aerosol spray from pressured container
or dispenser which contains a suitable propellant, e.g., a gas such
as carbon dioxide, or a nebulizer.
[0219] Systemic administration can also be by transmucosal or
transdermal means. For transmucosal or transdermal administration,
penetrants appropriate to the barrier to be permeated are used in
the formulation. Such penetrants are generally known in the art,
and include, for example, for transmucosal administration,
detergents, bile salts, and fusidic acid derivatives. Transmucosal
administration can be accomplished through the use of nasal sprays
or suppositories. For transdermal administration, the active
compounds are formulated into ointments, salves, gels, or creams as
generally known in the art.
[0220] The compounds can also be prepared in the form of
suppositories (e.g., with conventional suppository bases such as
cocoa butter and other glycerides) or retention enemas for rectal
delivery.
[0221] In one embodiment, the active compounds are prepared with
carriers that will protect the compound against rapid elimination
from the body, such as a controlled release formulation, including
implants and microencapsulated delivery systems. Biodegradable,
biocompatible polymers can be used, such as ethylene vinyl acetate,
polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and
polylactic acid. Methods for preparation of such formulations will
be apparent to those skilled in the art. The materials can also be
obtained commercially from Alza Corporation and Nova
Pharmaceuticals, Inc. Liposomal suspensions (including liposomes
targeted to infected cells with monoclonal antibodies to viral
antigens) can also be used as pharmaceutically acceptable carriers.
These can be prepared according to methods known to those skilled
in the art, for example, as described in U.S. Pat. No.
4,522,811.
[0222] It is especially advantageous to formulate oral or
parenteral compositions in dosage unit form for ease of
administration and uniformity of dosage. Dosage unit form as used
herein refers to physically discrete units suited as unitary
dosages for the subject to be treated; each unit containing a
predetermined quantity of active compound calculated to produce the
desired therapeutic effect in association with the required
pharmaceutical carrier. The specification for the dosage unit forms
of the invention are dictated by and directly dependent on the
unique characteristics of the active compound and the particular
therapeutic effect to be achieved, and the limitations inherent in
the art of compounding such an active compound for the treatment of
individuals.
[0223] The nucleic acid molecules of the invention can be inserted
into vectors and used as gene therapy vectors. Gene therapy vectors
can be delivered to a subject by, for example, intravenous
injection, local administration (see, e.g., U.S. Pat. No.
5,328,470) or by stereotactic injection (see, e.g., Chen, et al.,
1994. Proc. Natl. Acad. Sci. USA 91: 3054-3057). The pharmaceutical
preparation of the gene therapy vector can include the gene therapy
vector in an acceptable diluent, or can comprise a slow release
matrix in which the gene delivery vehicle is imbedded.
Alternatively, where the complete gene delivery vector can be
produced intact from recombinant cells, e.g., retroviral vectors,
the pharmaceutical preparation can include one or more cells that
produce the gene delivery system.
[0224] The pharmaceutical compositions can be included in a
container, pack, or dispenser together with instructions for
administration.
[0225] Screening and Detection Methods
[0226] The isolated nucleic acid molecules of the invention can be
used to express NOVX protein (e.g., via a recombinant expression
vector in a host cell in gene therapy applications), to detect NOVX
mRNA (e.g., in a biological sample) or a genetic lesion in A NOVX
gene, and to modulate NOVX activity, as described further, below.
In addition, the NOVX proteins can be used to screen drugs or
compounds that modulate the NOVX protein activity or expression as
well as to treat disorders characterized by insufficient or
excessive production of NOVX protein or production of NOVX protein
forms that have decreased or aberrant activity compared to NOVX
wild-type protein (e.g.; diabetes (regulates insulin release);
obesity (binds and transport lipids); metabolic disturbances
associated with obesity, the metabolic syndrome X as well as
anorexia and wasting disorders associated with chronic diseases and
various cancers, and infectious disease(possesses anti-microbial
activity) and the various dyslipidemias. In addition, the anti-NOVX
antibodies of the invention can be used to detect and isolate NOVX
proteins and modulate NOVX activity. In yet a further aspect, the
invention can be used in methods to influence appetite, absorption
of nutrients and the disposition of metabolic substrates in both a
positive and negative fashion.
[0227] The invention further pertains to novel agents identified by
the screening assays described herein and uses thereof for
treatments as described, supra.
[0228] Screening Assays
[0229] The invention provides a method (also referred to herein as
a "screening assay") for identifying modulators, i.e., candidate or
test compounds or agents (e.g., peptides, peptidomimetics, small
molecules or other drugs) that bind to NOVX proteins or have a
stimulatory or inhibitory effect on, e.g., NOVX protein expression
or NOVX protein activity. The invention also includes compounds
identified in the screening assays described herein.
[0230] In one embodiment, the invention provides assays for
screening candidate or test compounds which bind to or modulate the
activity of the membrane-bound form of A NOVX protein or
polypeptide or biologically-active portion thereof. The test
compounds of the invention can be obtained using any of the
numerous approaches in combinatorial library methods known in the
art, including: biological libraries; spatially addressable
parallel solid phase or solution phase libraries; synthetic library
methods requiring deconvolution; the "one-bead one-compound"
library method; and synthetic library methods using affinity
chromatography selection. The biological library approach is
limited to peptide libraries, while the other four approaches are
applicable to peptide, non-peptide oligomer or small molecule
libraries of compounds. See, e.g., Lam, 1997. Anticancer Drug
Design 12: 145.
[0231] A "small molecule" as used herein, is meant to refer to a
composition that has a molecular weight of less than about 5 kD and
most preferably less than about 4 kD. Small molecules can be, e.g.,
nucleic acids, peptides, polypeptides, peptidomimetics,
carbohydrates, lipids or other organic or inorganic molecules.
Libraries of chemical and/or biological mixtures, such as fungal,
bacterial, or algal extracts, are known in the art and can be
screened with any of the assays of the invention.
[0232] Examples of methods for the synthesis of molecular libraries
can be found in the art, for example in: DeWitt, et al., 1993.
Proc. Natl. Acad. Sci. U.S.A. 90: 6909; Erb, et al., 1994. Proc.
Natl. Acad. Sci. U.S.A. 91: 11422; Zuckermann, et al., 1994. J.
Med. Chem. 37: 2678; Cho, et al., 1993. Science 261: 1303; Carrell,
et al., 1994. Angew. Chem. Int. Ed. Engl. 33: 2059; Carell, et al.,
1994. Angew. Chem. Int. Ed. Engl. 33: 2061; and Gallop, et al.,
1994. J. Med. Chem. 37: 1233.
[0233] Libraries of compounds may be presented in solution (e.g.,
Houghten, 1992. Biotechniques 13: 412-421), or on beads (Lam,
1-991. Nature 354: 82-84), on chips (Fodor, 1993. Nature 364:
555-556), bacteria (Ladner, U.S. Pat. No. 5,223,409), spores
(Ladner, U.S. Pat. No. 5,233,409), plasmids (Cull, et al., 1992.
Proc. Natl. Acad. Sci. USA 89: 1865-1869) or on phage (Scott and
Smith, 1990. Science 249: 386-390; Devlin, 1990. Science 249:
404-406; Cwirla, et al., 1990. Proc. Natl. Acad. Sci. U.S.A. 87:
6378-6382; Felici, 1991. J. Mol. Biol. 222: 301-310; Ladner, U.S.
Pat. No. 5,233,409.).
[0234] In one embodiment, an assay is a cell-based assay in which a
cell which expresses a membrane-bound form of NOVX protein, or a
biologically-active portion thereof, on the cell surface is
contacted with a test compound and the ability of the test compound
to bind to A NOVX protein determined. The cell, for example, can of
mammalian origin or a yeast cell. Determining the ability of the
test compound to bind to the NOVX protein can be accomplished, for
example, by coupling the test compound with a radioisotope or
enzymatic label such that binding of the test compound to the NOVX
protein or biologically-active portion thereof can be determined by
detecting the labeled compound in a complex. For example, test
compounds can be labeled with .sup.125I, .sup.35S, .sup.14C, or
.sup.3H, either directly or indirectly, and the radioisotope
detected by direct counting of radioemission or by scintillation
counting. Alternatively, test compounds can be
enzymatically-labeled with, for example, horseradish peroxidase,
alkaline phosphatase, or luciferase, and the enzymatic label
detected by determination of conversion of an appropriate substrate
to product. In one embodiment, the assay comprises contacting a
cell which expresses a membrane-bound form of NOVX protein, or a
biologically-active portion thereof, on the cell surface with a
known compound which binds NOVX to form an assay mixture,
contacting the assay mixture with a test compound, and determining
the ability of the test compound to interact with A NOVX protein,
wherein determining the ability of the test compound to interact
with A NOVX protein comprises determining the ability of the test
compound to preferentially bind to NOVX protein or a
biologically-active portion thereof as compared to the known
compound.
[0235] In another embodiment, an assay is a cell-based assay
comprising contacting a cell expressing a membrane-bound form of
NOVX protein, or a biologically-active portion thereof, on the cell
surface with a test compound and determining the ability of the
test compound to modulate (e.g., stimulate or inhibit) the activity
of the NOVX protein or biologically-active portion thereof.
Determining the ability of the test compound to modulate the
activity of NOVX or a biologically-active portion thereof can be
accomplished, for example, by determining the ability of the NOVX
protein to bind to or interact with A NOVX target molecule. As used
herein, a "target molecule" is a molecule with which A NOVX protein
binds or interacts in nature, for example, a molecule on the
surface of a cell which expresses A NOVX interacting protein, a
molecule on the surface of a second cell, a molecule in the
extracellular milieu, a molecule associated with the internal
surface of a cell membrane or a cytoplasmic molecule. A NOVX target
molecule can be a non-NOVX molecule or A NOVX protein or
polypeptide of the invention. In one embodiment, A NOVX target
molecule is a component of a signal transduction pathway that
facilitates transduction of an extracellular signal (e.g. a signal
generated by binding of a compound to a membrane-bound NOVX
molecule) through the cell membrane and into the cell. The target,
for example, can be a second intercellular protein that has
catalytic activity or a protein that facilitates the association of
downstream signaling molecules with NOVX.
[0236] Determining the ability of the NOVX protein to bind to or
interact with A NOVX target molecule can be accomplished by one of
the methods described above for determining direct binding. In one
embodiment, determining the ability of the NOVX protein to bind to
or interact with A NOVX target molecule can be accomplished by
determining the activity of the target molecule. For example, the
activity of the target molecule can be determined by detecting
induction of a cellular second messenger of the target (i.e.
intracellular Ca.sup.2+, diacylglycerol, IP3, etc.), detecting
catalytic/enzymatic activity of the target an appropriate
substrate, detecting the induction of a reporter gene (comprising A
NOVX-responsive regulatory element operatively linked to a nucleic
acid encoding a detectable marker, e.g., luciferase), or detecting
a cellular response, for example, cell survival, cellular
differentiation, or cell proliferation.
[0237] In yet another embodiment, an assay of the invention is a
cell-free assay comprising contacting A NOVX protein or
biologically-active portion thereof with a test compound and
determining the ability of the test compound to bind to the NOVX
protein or biologically-active portion thereof. Binding of the test
compound to the NOVX protein can be determined either directly or
indirectly as described above. In one such embodiment, the assay
comprises contacting the NOVX protein or biologically-active
portion thereof with a known compound which binds NOVX to form an
assay mixture, contacting the assay mixture with a test compound,
and determining the ability of the test compound to interact with A
NOVX protein, wherein determining the ability of the test compound
to interact with A NOVX protein comprises determining the ability
of the test compound to preferentially bind to NOVX or
biologically-active portion thereof as compared to the known
compound.
[0238] In still another embodiment, an assay is a cell-free assay
comprising contacting NOVX protein or biologically-active portion
thereof with a test compound and determining the ability of the
test compound to modulate (e.g. stimulate or inhibit) the activity
of the NOVX protein or biologically-active portion thereof.
Determining the ability of the test compound to modulate the
activity of NOVX can be accomplished, for example, by determining
the ability of the NOVX protein to bind to A NOVX target molecule
by one of the methods described above for determining direct
binding. In an alternative embodiment, determining the ability of
the test compound to modulate the activity of NOVX protein can be
accomplished by determining the ability of the NOVX protein further
modulate A NOVX target molecule. For example, the
catalytic/enzymatic activity of the target molecule on an
appropriate substrate can be determined as described, supra.
[0239] In yet another embodiment, the cell-free assay comprises
contacting the NOVX protein or biologically-active portion thereof
with a known compound which binds NOVX protein to form an assay
mixture, contacting the assay mixture with a test compound, and
determining the ability of the test compound to interact with A
NOVX protein, wherein determining the ability of the test compound
to interact with A NOVX protein comprises determining the ability
of the NOVX protein to preferentially bind to or modulate the
activity of A NOVX target molecule.
[0240] The cell-free assays of the invention are amenable to use of
both the soluble form or the membrane-bound form of NOVX protein.
In the case of cell-free assays comprising the membrane-bound form
of NOVX protein, it may be desirable to utilize a solubilizing
agent such that the membrane-bound form of NOVX protein is
maintained in solution. Examples of such solubilizing agents
include non-ionic detergents such as n-octylglucoside,
n-dodecylglucoside, n-dodecylmaltoside, octanoyl-N-methylglucamide,
decanoyl-N-methylglucamide, Triton.RTM. X-100, Triton.RTM. X-114,
Thesit.RTM., Isotridecypoly(ethylene glycol ether).sub.n,
N-dodecyl-N,N-dimethyl-3-ammonio-1-propane sulfonate,
3-(3-cholamidopropyl) dimethylamminiol-1-propane sulfonate (CHAPS),
or 3-(3-cholamidopropyl)dimethylamminiol-2-hydroxy-1-propane
sulfonate (CHAPSO).
[0241] In more than one embodiment of the above assay methods of
the invention, it may be desirable to immobilize either NOVX
protein or its target molecule to facilitate separation of
complexed from uncomplexed forms of one or both of the proteins, as
well as to accommodate automation of the assay. Binding of a test
compound to NOVX protein, or interaction of NOVX protein with a
target molecule in the presence and absence of a candidate
compound, can be accomplished in any vessel suitable for containing
the reactants. Examples of such vessels include microtiter plates,
test tubes, and micro-centrifuge tubes. In one embodiment, a fusion
protein can be provided that adds a domain that allows one or both
of the proteins to be bound to a matrix. For example, GST-NOVX
fusion proteins or GST-target fusion proteins can be adsorbed onto
glutathione sepharose beads (Sigma Chemical, St. Louis, Mo.) or
glutathione derivatized microtiter plates, that are then combined
with the test compound or the test compound and either the
non-adsorbed target protein or NOVX protein, and the mixture is
incubated under conditions conducive to complex formation (e.g., at
physiological conditions for salt and pH). Following incubation,
the beads or microtiter plate wells are washed to remove any
unbound components, the matrix immobilized in the case of beads,
complex determined either directly or indirectly, for example, as
described, supra. Alternatively, the complexes can be dissociated
from the matrix, and the level of NOVX protein binding or activity
determined using standard techniques.
[0242] Other techniques for immobilizing proteins on matrices can
also be used in the screening assays of the invention. For example,
either the NOVX protein or its target molecule can be immobilized
utilizing conjugation of biotin and streptavidin. Biotinylated NOVX
protein or target molecules can be prepared from biotin-NHS
(N-hydroxy-succinimide) using techniques well-known within the art
(e.g., biotinylation kit, Pierce Chemicals, Rockford, Ill.), and
immobilized in the wells of streptavidin-coated 96 well plates
(Pierce Chemical). Alternatively, antibodies reactive with NOVX
protein or target molecules, but which do not interfere with
binding of the NOVX protein to its target molecule, can be
derivatized to the wells of the plate, and unbound target or NOVX
protein trapped in the wells by antibody conjugation. Methods for
detecting such complexes, in addition to those described above for
the GST-immobilized complexes, include immunodetection of complexes
using antibodies reactive with the NOVX protein or target molecule,
as well as enzyme-linked assays that rely on detecting an enzymatic
activity associated with the NOVX protein or target molecule.
[0243] In another embodiment, modulators of NOVX protein expression
are identified in a method wherein a cell is contacted with a
candidate compound and the expression of NOVX mRNA or protein in
the cell is determined. The level of expression of NOVX mRNA or
protein in the presence of the candidate compound is compared to
the level of expression of NOVX mRNA or protein in the absence of
the candidate compound. The candidate compound can then be
identified as a modulator of NOVX mRNA or protein expression based
upon this comparison. For example, when expression of NOVX mRNA or
protein is greater (i.e., statistically significantly greater) in
the presence of the candidate compound than in its absence, the
candidate compound is identified as a stimulator of NOVX mRNA or
protein expression. Alternatively, when expression of NOVX mRNA or
protein is less (statistically significantly less) in the presence
of the candidate compound than in its absence, the candidate
compound is identified as an inhibitor of NOVX mRNA or protein
expression. The level of NOVX mRNA or protein expression in the
cells can be determined by methods described herein for detecting
NOVX mRNA or protein.
[0244] In yet another aspect of the invention, the NOVX proteins
can be used as "bait proteins" in a two-hybrid assay or three
hybrid assay (see, e.g., U.S. Pat. No. 5,283,317; Zervos, et al.,
1993. Cell 72: 223-232; Madura, et al., 1993. J. Biol. Chem. 268:
12046-12054; Bartel, et al., 1993. Biotechniques 14: 920-924;
Iwabuchi, et al., 1993. Oncogene 8: 1693-1696; and Brent WO
94/10300), to identify other proteins that bind to or interact with
NOVX ("NOVX-binding proteins" or "NOVX-bp") and modulate NOVX
activity. Such NOVX-binding proteins are also likely to be involved
in the propagation of signals by the NOVX proteins as, for example,
upstream or downstream elements of the NOVX pathway.
[0245] The two-hybrid system is based on the modular nature of most
transcription factors, which consist of separable DNA-binding and
activation domains. Briefly, the assay utilizes two different DNA
constructs. In one construct, the gene that codes for NOVX is fused
to a gene encoding the DNA binding domain of a known transcription
factor (e.g., GAL-4). In the other construct, a DNA sequence, from
a library of DNA sequences, that encodes an unidentified protein
("prey" or "sample") is fused to a gene that codes for the
activation domain of the known transcription factor. If the "bait"
and the "prey" proteins are able to interact, in vivo, forming A
NOVX-dependent complex, the DNA-binding and activation domains of
the transcription factor are brought into close proximity. This
proximity allows transcription of a reporter gene (e.g., LacZ) that
is operably linked to a transcriptional regulatory site responsive
to the transcription factor. Expression of the reporter gene can be
detected and cell colonies containing the functional transcription
factor can be isolated and used to obtain the cloned gene that
encodes the protein which interacts with NOVX.
[0246] The invention further pertains to novel agents identified by
the aforementioned screening assays and uses thereof for treatments
as described herein.
[0247] Detection Assays
[0248] Portions or fragments of the cDNA sequences identified
herein (and the corresponding complete gene sequences) can be used
in numerous ways as polynucleotide reagents. By way of example, and
not of limitation, these sequences can be used to: (i) map their
respective genes on a chromosome; and, thus, locate gene regions
associated with genetic disease; (ii) identify an individual from a
minute biological sample (tissue typing); and (iii) aid in forensic
identification of a biological sample. Some of these applications
are described in the subsections, below.
[0249] Chromosome Mapping
[0250] Once the sequence (or a portion of the sequence) of a gene
has been isolated, this sequence can be used to map the location of
the gene on a chromosome. This process is called chromosome
mapping. Accordingly, portions or fragments of the NOVX sequences,
SEQ ID NOS:2n-1, wherein n is an integer between 1 and 54, or
fragments or derivatives thereof, can be used to map the location
of the NOVX genes, respectively, on a chromosome. The mapping of
the NOVX sequences to chromosomes is an important first step in
correlating these sequences with genes associated with disease.
[0251] Briefly, NOVX genes can be mapped to chromosomes by
preparing PCR primers (preferably 15-25 bp in length) from the NOVX
sequences. Computer analysis of the NOVX, sequences can be used to
rapidly select primers that do not span more than one exon in the
genomic DNA, thus complicating the amplification process. These
primers can then be used for PCR screening of somatic cell hybrids
containing individual human chromosomes. Only those hybrids
containing the human gene corresponding to the NOVX sequences will
yield an amplified fragment.
[0252] Somatic cell hybrids are prepared by fusing somatic cells
from different mammals (e.g., human and mouse cells). As hybrids of
human and mouse cells grow and divide, they gradually lose human
chromosomes in random order, but retain the mouse chromosomes. By
using media in which mouse cells cannot grow, because they lack a
particular enzyme, but in which human cells can, the one human
chromosome that contains the gene encoding the needed enzyme will
be retained. By using various media, panels of hybrid cell lines
can be established. Each cell line in a panel contains either a
single human chromosome or a small number of human chromosomes, and
a full set of mouse chromosomes, allowing easy mapping of
individual genes to specific human chromosomes. See, e.g.,
D'Eustachio, et al., 1983. Science 220: 919-924. Somatic cell.
hybrids containing only fragments of human chromosomes can also be
produced by using human chromosomes with translocations and
deletions.
[0253] PCR mapping of somatic cell hybrids is a rapid procedure for
assigning a particular sequence to a particular chromosome. Three
or more sequences can be assigned per day using a single thermal
cycler. Using the NOVX sequences to design oligonucleotide primers,
sub-localization can be achieved with panels of fragments from
specific chromosomes.
[0254] Fluorescence in situ hybridization (FISH) of a DNA sequence
to a metaphase chromosomal spread can further be used to provide a
precise chromosomal location in one step. Chromosome spreads can be
made using cells whose division has been blocked in metaphase by a
chemical like colcemid that disrupts the mitotic spindle. The
chromosomes can be treated briefly with trypsin, and then stained
with Giemsa. A pattern of light and dark bands develops on each
chromosome, so that the chromosomes can be identified individually.
The FISH technique can be used with a DNA sequence as short as 500
or 600 bases. However, clones larger than 1,000 bases have a higher
likelihood of binding to a unique chromosomal location with
sufficient signal intensity for simple detection. Preferably 1,000
bases, and more preferably 2,000 bases, will suffice to get good
results at a reasonable amount of time. For a review of this
technique, see, Verma, et al., HUMAN CHROMOSOMES: A MANUAL OF BASIC
TECHNIQUES (Pergamon Press, New York 1988).
[0255] Reagents for chromosome mapping can be used individually to
mark a single chromosome or a single site on that chromosome, or
panels of reagents can be used for marking multiple sites and/or
multiple chromosomes. Reagents corresponding to noncoding regions
of the genes actually are preferred for mapping purposes. Coding
sequences are more likely to be conserved within gene families,
thus increasing the chance of cross hybridizations during
chromosomal mapping.
[0256] Once a sequence has been mapped to a precise chromosomal
location, the physical position of the sequence on the chromosome
can be correlated with genetic map data. Such data are found, e.g.,
in McKusick, MENDELIAN INHERITANCE IN MAN, available on-line
through Johns Hopkins University Welch Medical Library). The
relationship between genes and disease, mapped to the same
chromosomal region, can then be identified through linkage analysis
(co-inheritance of physically adjacent genes), described in, e.g.,
Egeland, et al., 1987. Nature, 325: 783-787.
[0257] Moreover, differences in the DNA sequences between
individuals affected and unaffected with a disease associated with
the NOVX gene, can be determined. If a mutation is observed in some
or all of the affected individuals but not in any unaffected
individuals, then the mutation is likely to be the causative agent
of the particular disease. Comparison of affected and unaffected
individuals generally involves first looking for structural
alterations in the chromosomes, such as deletions or translocations
that are visible from chromosome spreads or detectable using PCR
based on that DNA sequence. Ultimately, complete sequencing of
genes from several individuals can be performed to confirm the
presence of a mutation and to distinguish mutations from
polymorphisms.
[0258] Tissue Typing
[0259] The NOVX sequences of the invention can also be used to
identify individuals from minute biological samples. In this
technique, an individual's genomic DNA is digested with one or more
restriction enzymes, and probed on a Southern blot to yield unique
bands for identification. The sequences of the invention are useful
as additional DNA markers for RFLP ("restriction fragment length
polymorphisms," described in U.S. Pat. No. 5,272,057).
[0260] Furthermore, the sequences of the invention can be used to
provide an alternative technique that determines the actual
base-by-base DNA sequence of selected portions of an individual's
genome. Thus, the NOVX sequences described herein can be used to
prepare two PCR primers from the 5'- and 3'-termini of the
sequences. These primers can then be used to amplify an
individual's DNA and subsequently sequence it.
[0261] Panels of corresponding DNA sequences from individuals,
prepared in this manner, can provide unique individual
identifications, as each individual will have a unique set of such
DNA sequences due to allelic differences. The sequences of the
invention can be used to obtain such identification sequences from
individuals and from tissue. The NOVX sequences of the invention
uniquely represent portions of the human genome. Allelic variation
occurs to some degree in the coding regions of these sequences, and
to a greater degree in the noncoding regions. It is estimated that
allelic variation between individual humans occurs with a frequency
of about once per each 500 bases. Much of the allelic variation is
due to single nucleotide polymorphisms (SNPs), which include
restriction fragment length polymorphisms (RFLPs).
[0262] Each of the sequences described herein can, to some degree,
be used as a standard against which DNA from an individual can be
compared for identification purposes. Because greater numbers of
polymorphisms occur in the noncoding regions, fewer sequences are
necessary to differentiate individuals. The noncoding sequences can
comfortably provide positive individual identification with a panel
of perhaps 10 to 1,000 primers that each yield a noncoding
amplified sequence of 100 bases. If predicted coding sequences,
such as those in SEQ ID NOS:2n-1, wherein n is an integer between 1
and 54, are used, a more appropriate number of primers for positive
individual identification would be 500-2,000.
[0263] Predictive Medicine
[0264] The invention also pertains to the field of predictive
medicine in which diagnostic assays, prognostic assays,
pharmacogenomics, and monitoring clinical trials are used for
prognostic (predictive) purposes to thereby treat an individual
prophylactically. Accordingly, one aspect of the invention relates
to diagnostic assays for determining NOVX protein and/or nucleic
acid expression as well as NOVX activity, in the context of a
biological sample (e.g., blood, serum, cells, tissue) to thereby
determine whether an individual is afflicted with a disease or
disorder, or is at risk of developing a disorder, associated with
aberrant NOVX expression or activity. The disorders include
metabolic disorders, diabetes, obesity, infectious disease,
anorexia, cancer-associated cachexia, cancer, neurodegenerative
disorders, Alzheimer's Disease, Parkinson's Disorder, immune
disorders, and hematopoietic disorders, and the various
dyslipidemias, metabolic disturbances associated with obesity, the
metabolic syndrome X and wasting disorders associated with chronic
diseases and various cancers. The invention also provides for
prognostic (or predictive) assays for determining whether an
individual is at risk of developing a disorder associated with NOVX
protein, nucleic acid expression or activity. For example,
mutations in A NOVX gene can be assayed in a biological sample.
Such assays can be used for prognostic or predictive purpose to
thereby prophylactically treat an individual prior to the onset of
a disorder characterized by or associated with NOVX protein,
nucleic acid expression, or biological activity.
[0265] Another aspect of the invention provides methods for
determining NOVX protein, nucleic acid expression or activity in an
individual to thereby select appropriate therapeutic or
prophylactic agents for that individual (referred to herein as
"pharmacogenomics"). Pharmacogenomics allows for the selection of
agents (e.g., drugs) for therapeutic or prophylactic treatment of
an individual based on the genotype of the individual (e.g., the
genotype of the individual examined to determine the ability of the
individual to respond to a particular agent.) Yet another aspect of
the invention pertains to monitoring the influence of agents (e.g.,
drugs, compounds) on the expression or activity of NOVX in clinical
trials.
[0266] These and other agents are described in further detail in
the following sections.
[0267] Diagnostic Assays
[0268] An exemplary method for detecting the presence or absence of
NOVX in a biological sample involves obtaining a biological sample
from a test subject and contacting the biological sample with a
compound or an agent capable of detecting NOVX protein or nucleic
acid (e.g., mRNA, genomic DNA) that encodes NOVX protein such that
the presence of NOVX is detected in the biological sample. An agent
for detecting NOVX mRNA or genomic DNA is a labeled nucleic acid
probe capable of hybridizing to NOVX mRNA or genomic DNA. The
nucleic acid probe can be, for example, a full-length NOVX nucleic
acid, such as the nucleic acid of SEQ ID NOS:2n-1, wherein n is an
integer between 1 and 54, or a portion thereof, such as an
oligonucleotide of at least 15, 30, 50, 100, 250 or 500 nucleotides
in length and sufficient to specifically hybridize under stringent
conditions to NOVX mRNA or genomic DNA. Other suitable probes for
use in the diagnostic assays of the invention are described
herein.
[0269] An agent for detecting NOVX protein is an antibody capable
of binding to NOVX protein, preferably an antibody with a
detectable label. Antibodies can be polyclonal, or more preferably,
monoclonal. An intact antibody, or a fragment thereof (e.g., Fab or
F(ab').sub.2) can be used. The term "labeled", with regard to the
probe or antibody, is intended to encompass direct labeling of the
probe or antibody by coupling (i.e., physically linking) a
detectable substance to the probe or antibody, as well as indirect
labeling of the probe or antibody by reactivity with another
reagent that is directly labeled. Examples of indirect labeling
include detection of a primary antibody using a
fluorescently-labeled secondary antibody and end-labeling of a DNA
probe with biotin such that it can be detected with
fluorescently-labeled streptavidin. The term "biological sample" is
intended to include tissues, cells and biological fluids isolated
from a subject, as well as tissues, cells and fluids present within
a subject. That is, the detection method of the invention can be
used to detect NOVX mRNA, protein, or genomic DNA in a biological
sample in vitro as well as in vivo. For example, in vitro
techniques for detection of NOVX mRNA include Northern
hybridizations and in situ hybridizations. In vitro techniques for
detection of NOVX protein include enzyme linked immunosorbent
assays (ELISAs), Western blots, immunoprecipitations, and
immunofluorescence. In vitro techniques for detection of NOVX
genomic DNA include Southern hybridizations. Furthermore, in vivo
techniques for detection of NOVX protein include introducing into a
subject a labeled anti-NOVX antibody. For example, the antibody can
be labeled with a radioactive marker whose presence and location in
a subject can be detected by standard imaging techniques.
[0270] In one embodiment, the biological sample contains protein
molecules from the test subject. Alternatively, the biological
sample can contain mRNA molecules from the test subject or genomic
DNA molecules from the test subject. A preferred biological sample
is a peripheral blood leukocyte sample isolated by conventional
means from a subject.
[0271] In another embodiment, the methods further involve obtaining
a control biological sample from a control subject, contacting the
control sample with a compound or agent capable of detecting NOVX
protein, mRNA, or genomic DNA, such that the presence of NOVX
protein, mRNA or genomic DNA is detected in the biological sample,
and comparing the presence of NOVX protein, mRNA or genomic DNA in
the control sample with the presence of NOVX protein, mRNA or
genomic DNA in the test sample.
[0272] The invention also encompasses kits for detecting the
presence of NOVX in a biological sample. For example, the kit can
comprise: a labeled compound or agent capable of detecting NOVX
protein or mRNA in a biological sample; means for determining the
amount of NOVX in the sample; and means for comparing the amount of
NOVX in the sample with a standard. The compound or agent can be
packaged in a suitable container. The kit can further comprise
instructions for using the kit to detect NOVX protein or nucleic
acid.
[0273] Prognostic Assays
[0274] The diagnostic methods described herein can furthermore be
utilized to identify subjects having or at risk of developing a
disease or disorder associated with aberrant NOVX expression or
activity. For example, the assays described herein, such as the
preceding diagnostic assays or the following assays, can be
utilized to identify a subject having or at risk of developing a
disorder associated with NOVX protein, nucleic acid expression or
activity. Alternatively, the prognostic assays can be utilized to
identify a subject having or at risk for developing a disease or
disorder. Thus, the invention provides a method for identifying a
disease or disorder associated with aberrant NOVX expression or
activity in which a test sample is obtained from a subject and NOVX
protein or nucleic acid (e.g., mRNA, genomic DNA) is detected,
wherein the presence of NOVX protein or nucleic acid is diagnostic
for a subject having or at risk of developing a disease or disorder
associated with aberrant NOVX expression or activity. As used
herein, a "test sample" refers to a biological sample obtained from
a subject of interest. For example, a test sample can be a
biological fluid (e.g., serum), cell sample, or tissue.
[0275] Furthermore, the prognostic assays described herein can be
used to determine whether a subject can be administered an agent
(e.g., an agonist, antagonist, peptidomimetic, protein, peptide,
nucleic acid, small molecule, or other drug candidate) to treat a
disease or disorder associated with aberrant NOVX expression or
activity. For example, such methods can be used to determine
whether a subject can be effectively treated with an agent for a
disorder. Thus, the invention provides methods for determining
whether a subject can be effectively treated with an agent for a
disorder associated with aberrant NOVX expression or activity in
which a test sample is obtained and NOVX protein or nucleic acid is
detected (e.g., wherein the presence of NOVX protein or nucleic
acid is diagnostic for a subject that can be administered the agent
to treat a disorder associated with aberrant NOVX expression or
activity).
[0276] The methods of the invention can also be used to detect
genetic lesions in A NOVX gene, thereby determining if a subject
with the lesioned gene is at risk for a disorder characterized by
aberrant cell proliferation and/or differentiation. In various
embodiments, the methods include detecting, in a sample of cells
from the subject, the presence or absence of a genetic lesion
characterized by at least one of an alteration affecting the
integrity of a gene encoding A NOVX-protein, or the misexpression
of the NOVX gene. For example, such genetic lesions can be detected
by ascertaining the existence of at least one of: (i) a deletion of
one or more nucleotides from A NOVX gene; (ii) an addition of one
or more nucleotides to A NOVX gene; (iii) a substitution of one or
more nucleotides of A NOVX gene, (iv) a chromosomal rearrangement
of A NOVX gene; (v) an alteration in the level of a messenger RNA
transcript of A NOVX gene, (vi) aberrant modification of A NOVX
gene, such as of the methylation pattern of the genomic DNA, (vii)
the presence of a non-wild-type splicing pattern of a messenger RNA
transcript of A NOVX gene, (viii) a non-wild-type level of A NOVX
protein, (ix) allelic loss of A NOVX gene, and (x) inappropriate
post-translational modification of A NOVX protein. As described
herein, there are a large number of assay techniques known in the
art which can be used for detecting lesions in A NOVX gene. A
preferred biological sample is a peripheral blood leukocyte sample
isolated by conventional means from a subject. However, any
biological sample containing nucleated cells may be used,
including, for example, buccal mucosal cells.
[0277] In certain embodiments, detection of the lesion involves the
use of a probe/primer in a polymerase chain reaction (PCR) (see,
e.g., U.S. Pat. Nos. 4,683,195 and 4,683,202), such as anchor PCR
or RACE PCR, or, alternatively, in a ligation chain reaction (LCR)
(see, e.g., Landegran, et al., 1988. Science 241: 1077-1080; and
Nakazawa, et al., 1994. Proc. Natl. Acad. Sci. USA 91: 360-364),
the latter of which can be particularly useful for detecting point
mutations in the NOVX-gene (see, Abravaya, et al., 1995. Nucl.
Acids Res. 23: 675-682). This method can include the steps of
collecting a sample of cells from a patient, isolating nucleic acid
(e.g., genomic, mRNA or both) from the cells of the sample,
contacting the nucleic acid sample with one or more primers that
specifically hybridize to A NOVX gene under conditions such that
hybridization and amplification of the NOVX gene (if present)
occurs, and detecting the presence or absence of an amplification
product, or detecting the size of the amplification product and
comparing the length to a control sample. It is anticipated that
PCR and/or LCR may be desirable to use as a preliminary
amplification step in conjunction with any of the techniques used
for detecting mutations described herein.
[0278] Alternative amplification methods include: self sustained
sequence replication (see, Guatelli, et al., 1990. Proc. Natl.
Acad. Sci. USA 87: 1874-1878), transcriptional amplification system
(see, Kwoh, et al., 1989. Proc. Natl. Acad. Sci. USA 86:
1173-1177); Q.beta.Replicase (see, Lizardi, et al, 1988.
BioTechnology 6: 1197), or any other nucleic acid amplification
method, followed by the detection of the amplified molecules using
techniques well known to those of skill in the art. These detection
schemes are especially useful for the detection of nucleic acid
molecules if such molecules are present in very low numbers.
[0279] In an alternative embodiment, mutations in A NOVX gene from
a sample cell can be identified by alterations in restriction
enzyme cleavage patterns. For example, sample and control DNA is
isolated, amplified (optionally), digested with one or more
restriction endonucleases, and fragment length sizes are determined
by gel electrophoresis and compared. Differences in fragment length
sizes between sample and control DNA indicates mutations in the
sample DNA. Moreover, the use of sequence specific ribozymes (see,
e.g., U.S. Pat. No. 5,493,531) can be used to score for the
presence of specific mutations by development or loss of a ribozyme
cleavage site.
[0280] In other embodiments, genetic mutations in NOVX can be
identified by hybridizing a sample and control nucleic acids, e.g.,
DNA or RNA, to high-density arrays containing hundreds or thousands
of oligonucleotides probes. See, e.g., Cronin, et al., 1996. Human
Mutation 7: 244-255; Kozal, et al., 1996. Nat. Med. 2: 753-759. For
example, genetic mutations in NOVX can be identified in two
dimensional arrays containing light-generated DNA probes as
described in Cronin, et al., supra. Briefly, a first hybridization
array of probes can be used to scan through long stretches of DNA
in a sample and control to identify base changes between the
sequences by making linear arrays of sequential overlapping probes.
This step allows the identification of point mutations. This is
followed by a second hybridization array that allows the
characterization of specific mutations by using smaller,
specialized probe arrays complementary to all variants or mutations
detected. Each mutation array is composed of parallel probe sets,
one complementary to the wild-type gene and the other complementary
to the mutant gene.
[0281] In yet another embodiment, any of a variety of sequencing
reactions known in the art can be used to directly sequence the
NOVX gene and detect mutations by comparing the sequence of the
sample NOVX with the corresponding wild-type (control) sequence.
Examples of sequencing reactions include those based on techniques
developed by Maxim and Gilbert, 1977. Proc. Natl. Acad. Sci. USA
74: 560 or Sanger, 1977. Proc. Natl. Acad. Sci. USA 74: 5463. It is
also contemplated that any of a variety of automated sequencing
procedures can be utilized when performing the diagnostic assays
(see, e.g., Naeve, et al., 1995. Biotechniques 19: 448), including
sequencing by mass spectrometry (see, e.g., PCT International
Publication No. WO 94/16101; Cohen, et al., 1996. Adv.
Chromatography 36: 127-162; and Griffin, et al., 1993. Appl.
Biochem. Biotechnol. 38: 147-159).
[0282] Other methods for detecting mutations in the NOVX gene
include methods in which protection from cleavage agents is used to
detect mismatched bases in RNA/RNA or RNA/DNA heteroduplexes. See,
e.g., Myers, et al., 1985. Science 230: 1242. In general, the art
technique of "mismatch cleavage" starts by providing heteroduplexes
of formed by hybridizing (labeled) RNA or DNA containing the
wild-type NOVX sequence with potentially mutant RNA or DNA obtained
from a tissue sample. The double-stranded duplexes are treated with
an agent that cleaves single-stranded regions of the duplex such as
which will exist due to basepair mismatches between the control and
sample strands. For instance, RNA/DNA duplexes can be treated with
RNase and DNA/DNA hybrids treated with S.sub.1 nuclease to
enzymatically digesting the mismatched regions. In other
embodiments, either DNA/DNA or RNA/DNA duplexes can be treated with
hydroxylamine or osmium tetroxide and with piperidine in order to
digest mismatched regions. After digestion of the mismatched
regions, the resulting material is then separated by size on
denaturing polyacrylamide gels to determine the site of mutation.
See, e.g., Cotton, et al., 1988. Proc. Natl. Acad. Sci. USA 85:
4397; Saleeba, et al., 1992. Methods Enzymol. 217: 286-295. In an
embodiment, the control DNA or RNA can be labeled for
detection.
[0283] In still another embodiment, the mismatch cleavage reaction
employs one or more proteins that recognize mismatched base pairs
in double-stranded DNA (so called "DNA mismatch repair" enzymes) in
defined systems for detecting and mapping point mutations in NOVX
cDNAs obtained from samples of cells. For example, the mutY enzyme
of E. coli cleaves A at G/A mismatches and the thymidine DNA
glycosylase from HeLa cells cleaves T at G/T mismatches. See, e.g.,
Hsu, et al., 1994. Carcinogenesis 15: 1657-1662. According to an
exemplary embodiment, a probe based on A NOVX sequence, e.g., a
wild-type NOVX sequence, is hybridized to a cDNA or other DNA
product from a test cell(s). The duplex is treated with a DNA
mismatch repair enzyme, and the cleavage products, if any, can be
detected from electrophoresis protocols or the like. See, e.g.,
U.S. Pat. No. 5,459,039.
[0284] In other embodiments, alterations in electrophoretic
mobility will be used to identify mutations in NOVX genes. For
example, single strand conformation polymorphism (SSCP) may be used
to detect differences in electrophoretic mobility between mutant
and wild type nucleic acids. See, e.g., Orita, et al., 1989. Proc.
Natl. Acad. Sci. USA: 86: 2766; Cotton, 1993. Mutat. Res. 285:
125-144; Hayashi, 1992. Genet. Anal. Tech. Appl. 9: 73-79.
Single-stranded DNA fragments of sample and control NOVX nucleic
acids will be denatured and allowed to renature. The secondary
structure of single-stranded nucleic acids varies according to
sequence, the resulting alteration in electrophoretic mobility
enables the detection of even a single base change. The DNA
fragments may be labeled or detected with labeled probes. The
sensitivity of the assay may be enhanced by using RNA (rather than
DNA), in which the secondary structure is more sensitive to a
change in sequence. In one embodiment, the subject method utilizes
heteroduplex analysis to separate double stranded heteroduplex
molecules on the basis of changes in electrophoretic mobility. See,
e.g., Keen, et al., 1991. Trends Genet. 7: 5.
[0285] In yet another embodiment, the movement of mutant or
wild-type fragments in polyacrylamide gels containing a gradient of
denaturant is assayed using denaturing gradient gel electrophoresis
(DGGE). See, e.g., Myers, et al., 1985. Nature 313: 495. When DGGE
is used as the method of analysis, DNA will be modified to insure
that it does not completely denature, for example by adding a GC
clamp of approximately 40 bp of high-melting GC-rich DNA by PCR. In
a further embodiment, a temperature gradient is used in place of a
denaturing gradient to identify differences in the mobility of
control and sample DNA. See, e.g., Rosenbaum and Reissner, 1987.
Biophys. Chem. 265: 12753.
[0286] Examples of other techniques for detecting point mutations
include, but are not limited to, selective oligonucleotide
hybridization, selective amplification, or selective primer
extension. For example, oligonucleotide primers may be prepared in
which the known mutation is placed centrally and then hybridized to
target DNA under conditions that permit hybridization only if a
perfect match is found. See, e.g., Saiki, et al., 1986. Nature 324:
163; Saiki, et al., 1989. Proc. Natl. Acad. Sci. USA 86: 6230. Such
allele specific oligonucleotides are hybridized to PCR amplified
target DNA or a number of different mutations when the
oligonucleotides are attached to the hybridizing membrane and
hybridized with labeled target DNA.
[0287] Alternatively, allele specific amplification technology that
depends on selective PCR amplification may be used in conjunction
with the instant invention. Oligonucleotides used as primers for
specific amplification may carry the mutation of interest in the
center of the molecule (so that amplification depends on
differential hybridization; see, e.g., Gibbs, et al., 1989. Nucl.
Acids Res. 17: 2437-2448) or at the extreme 3'-terminus of one
primer where, under appropriate conditions, mismatch can prevent,
or reduce polymerase extension (see, e.g., Prossner, 1993. Tibtech.
11: 238). In addition it may be desirable to introduce a novel
restriction site in the region of the mutation to create
cleavage-based detection. See, e.g., Gasparini, et al., 1992. Mol.
Cell Probes 6: 1. It is anticipated that in certain embodiments
amplification may also be performed using Taq ligase for
amplification. See, e.g., Barany, 1991. Proc. Natl. Acad. Sci. USA
88: 189. In such cases, ligation will occur only if there is a
perfect match at the 3'-terminus of the 5' sequence, making it
possible to detect the presence of a known mutation at a specific
site by looking for the presence or absence of amplification.
[0288] The methods described herein may be performed, for example,
by utilizing pre-packaged diagnostic kits comprising at least one
probe nucleic acid or antibody reagent described herein, which may
be conveniently used, e.g., in clinical settings to diagnose
patients exhibiting symptoms or family history of a disease or
illness involving A NOVX gene.
[0289] Furthermore, any cell type or tissue, preferably peripheral
blood leukocytes, in which NOVX is expressed may be utilized in the
prognostic assays described herein. However, any biological sample
containing nucleated cells may be used, including, for example,
buccal mucosal cells.
[0290] Pharmacogenomics
[0291] Agents, or modulators that have a stimulatory or inhibitory
effect on NOVX activity (e.g., NOVX gene expression), as identified
by a screening assay described herein can be administered to
individuals to treat (prophylactically or therapeutically)
disorders (The disorders include metabolic disorders, diabetes,
obesity, infectious disease, anorexia, cancer-associated cachexia,
cancer, neurodegenerative disorders, Alzheimer's Disease,
Parkinson's Disorder, immune disorders, and hematopoietic
disorders, and the various dyslipidemias, metabolic disturbances
associated with obesity, the metabolic syndrome X and wasting
disorders associated with chronic diseases and various cancers.) In
conjunction with such treatment, the pharmacogenomics (i.e., the
study of the relationship between an individual's genotype and that
individual's response to a foreign compound or drug) of the
individual may be considered. Differences in metabolism of
therapeutics can lead to severe toxicity or therapeutic failure by
altering the relation between dose and blood concentration of the
pharmacologically active drug. Thus, the pharmacogenomics of the
individual permits the selection of effective agents (e.g., drugs)
for prophylactic or therapeutic treatments based on a consideration
of the individual's genotype. Such pharmacogenomics can further be
used to determine appropriate dosages and therapeutic regimens.
Accordingly, the activity of NOVX protein, expression of NOVX
nucleic acid, or mutation content of NOVX genes in an individual
can be determined to thereby select appropriate agent(s) for
therapeutic or prophylactic treatment of the individual.
[0292] Pharmacogenomics deals with clinically significant
hereditary variations in the response to drugs due to altered drug
disposition and abnormal action in affected persons. See e.g.,
Eichelbaum, 1996. Clin. Exp. Pharmacol. Physiol., 23: 983-985;
Linder, 1997. Clin. Chem., 43: 254-266. In general, two types of
pharmacogenetic conditions can be differentiated. Genetic
conditions transmitted as a single factor altering the way drugs
act on the body (altered drug action) or genetic conditions
transmitted as single factors altering the way the body acts on
drugs (altered drug metabolism). These pharmacogenetic conditions
can occur either as rare defects or as polymorphisms. For example,
glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common
inherited enzymopathy in which the main clinical complication is
hemolysis after ingestion of oxidant drugs (anti-malarials,
sulfonamides, analgesics, nitrofurans) and consumption of fava
beans.
[0293] As an illustrative embodiment, the activity of drug
metabolizing enzymes is a major determinant of both the intensity
and duration of drug action. The discovery of genetic polymorphisms
of drug metabolizing enzymes (e.g., N-acetyltransferase 2 (NAT 2)
and cytochrome Pregnancy Zone Protein Precursor enzymes CYP2D6 and
CYP2C19) has provided an explanation as to why some patients do not
obtain the expected drug effects or show exaggerated drug response
and serious toxicity after taking the standard and safe dose of a
drug. These polymorphisms are expressed in two phenotypes in the
population, the extensive metabolizer (EM) and poor metabolizer
(PM). The prevalence of PM is different among different
populations. For example, the gene coding for CYP2D6 is highly
polymorphic and several mutations have been identified in PM, which
all lead to the absence of functional CYP2D6. Poor metabolizers of
CYP2D6 and CYP2C19 quite frequently experience exaggerated drug
response and side effects when they receive standard doses. If a
metabolite is the active therapeutic moiety, PM show no therapeutic
response, as demonstrated for the analgesic effect of codeine
mediated by its CYP2D6-formed metabolite morphine. At the other
extreme are the so called ultra-rapid metabolizers who do not
respond to standard doses. Recently, the molecular basis of
ultra-rapid metabolism has been identified to be due to CYP2D6 gene
amplification.
[0294] Thus, the activity of NOVX protein, expression of NOVX
nucleic acid, or mutation content of NOVX genes in an individual
can be determined to thereby select appropriate agent(s) for
therapeutic or prophylactic treatment of the individual. In
addition, pharmacogenetic studies can be used to apply genotyping
of polymorphic alleles encoding drug-metabolizing enzymes to the
identification of an individual's drug responsiveness phenotype.
This knowledge, when applied to dosing or drug selection, can avoid
adverse reactions or therapeutic failure and thus enhance
therapeutic or prophylactic efficiency when treating a subject with
A NOVX modulator, such as a modulator identified by one of the
exemplary screening assays described herein.
[0295] Monitoring of Effects During Clinical Trials
[0296] Monitoring the influence of agents (e.g., drugs, compounds)
on the expression or activity of NOVX (e.g., the ability to
modulate aberrant cell proliferation and/or differentiation) can be
applied not only in basic drug screening, but also in clinical
trials. For example, the effectiveness of an agent determined by a
screening assay as described herein to increase NOVX gene
expression, protein levels, or upregulate NOVX activity, can be
monitored in clinical trails of subjects exhibiting decreased NOVX
gene expression, protein levels, or downregulated NOVX activity.
Alternatively, the effectiveness of an agent determined by a
screening assay to decrease NOVX gene expression, protein levels,
or downregulate NOVX activity, can be monitored in clinical trails
of subjects exhibiting increased NOVX gene expression, protein
levels, or upregulated NOVX activity. In such clinical trials, the
expression or activity of NOVX and, preferably, other genes that
have been implicated in, for example, a cellular proliferation or
immune disorder can be used as a "read out" or markers of the
immune responsiveness of a particular cell.
[0297] By way of example, and not of limitation, genes, including
NOVX, that are modulated in cells by treatment with an agent (e.g.,
compound, drug or small molecule) that modulates NOVX activity
(e.g., identified in a screening assay as described herein) can be
identified. Thus, to study the effect of agents on cellular
proliferation disorders, for example, in a clinical trial, cells
can be isolated and RNA prepared and analyzed for the levels of
expression of NOVX and other genes implicated in the disorder. The
levels of gene expression (i.e., a gene expression pattern) can be
quantified by Northern blot analysis or RT-PCR, as described
herein, or alternatively by measuring the amount of protein
produced, by one of the methods as described herein, or by
measuring the levels of activity of NOVX or other genes. In this
manner, the gene expression pattern can serve as a marker,
indicative of the physiological response of the cells to the agent.
Accordingly, this response state may be determined before, and at
various points during, treatment of the individual with the
agent.
[0298] In one embodiment, the invention provides a method for
monitoring the effectiveness of treatment of a subject with an
agent (e.g., an agonist, antagonist, protein, peptide,
peptidomimetic, nucleic acid, small molecule, or other drug
candidate identified by the screening assays described herein)
comprising the steps of (i) obtaining a pre-administration sample
from a subject prior to administration of the agent; (ii) detecting
the level of expression of A NOVX protein, mRNA, or genomic DNA in
the preadministration sample; (iii) obtaining one or more
post-administration samples from the subject; (iv) detecting the
level of expression or activity of the NOVX protein, mRNA, or
genomic DNA in the post-administration samples; (v) comparing the
level of expression or activity of the NOVX protein, mRNA, or
genomic DNA in the pre-administration sample with the NOVX protein,
mRNA, or genomic DNA in the post administration sample or samples;
and (vi) altering the administration of the agent to the subject
accordingly. For example, increased administration of the agent may
be desirable to increase the expression or activity of NOVX to
higher levels than detected, i.e., to increase the effectiveness of
the agent. Alternatively, decreased administration of the agent may
be desirable to decrease expression or activity of NOVX to lower
levels than detected, i.e., to decrease the effectiveness of the
agent.
[0299] Methods of Treatment
[0300] The invention provides for both prophylactic and therapeutic
methods of treating a subject at risk of (or susceptible to) a
disorder or having a disorder associated with aberrant NOVX
expression or activity. The disorders include cardiomyopathy,
atherosclerosis, hypertension, congenital heart defects, aortic
stenosis, atrial septal defect (ASD), atrioventricular (A-V) canal
defect, ductus arteriosus, pulmonary stenosis, subaortic stenosis,
ventricular septal defect (VSD), valve diseases, tuberous
sclerosis, scleroderma, obesity, transplantation,
adrenoleukodystrophy, congenital adrenal hyperplasia, prostate
cancer, neoplasm; adenocarcinoma, lymphoma, uterus cancer,
fertility, hemophilia, hypercoagulation, idiopathic
thrombocytopenic purpura, immunodeficiencies, graft versus host
disease, AIDS, bronchial asthma, Crohn's disease; multiple
sclerosis, treatment of Albright Hereditary Ostoeodystrophy, and
other diseases, disorders and conditions of the like.
[0301] These methods of treatment will be discussed more fully,
below.
[0302] Diseases and Disorders
[0303] Diseases and disorders that are characterized by increased
(relative to a subject not suffering from the disease or disorder)
levels or biological activity may be treated with Therapeutics that
antagonize (i.e., reduce or inhibit) activity. Therapeutics that
antagonize activity may be administered in a therapeutic or
prophylactic manner. Therapeutics that may be utilized include, but
are not limited to: (i) an aforementioned peptide, or analogs,
derivatives, fragments or homologs thereof; (ii) antibodies to an
aforementioned peptide; (iii) nucleic acids encoding an
aforementioned peptide; (iv) administration of antisense nucleic
acid and nucleic acids that are "dysfunctional" (i.e., due to a
heterologous insertion within the coding sequences of coding
sequences to an aforementioned peptide) that are utilized to
"knockout" endogenous function of an aforementioned peptide by
homologous recombination (see, e.g., Capecchi, 1989. Science 244:
1288-1292); or (v) modulators (i.e., inhibitors, agonists and
antagonists, including additional peptide mimetic of the invention
or antibodies specific to a peptide of the invention) that alter
the interaction between an aforementioned peptide and its binding
partner.
[0304] Diseases and disorders that are characterized by decreased
(relative to a subject not suffering from the disease or disorder)
levels or biological activity may be treated with Therapeutics that
increase (i.e., are agonists to) activity. Therapeutics that
upregulate activity may be administered in a therapeutic or
prophylactic manner. Therapeutics that may be utilized include, but
are not limited to, an aforementioned peptide, or analogs,
derivatives, fragments or homologs thereof; or an agonist that
increases bioavailability.
[0305] Increased or decreased levels can be readily detected by
quantifying peptide and/or RNA, by obtaining a patient tissue
sample (e.g., from biopsy tissue) and assaying it in vitro for RNA
or peptide levels, structure and/or activity of the expressed
peptides (or mRNAs of an aforementioned peptide). Methods that are
well-known within the art include, but are not limited to,
immunoassays (e.g., by Western blot analysis, immunoprecipitation
followed by sodium dodecyl sulfate (SDS) polyacrylamide gel
electrophoresis, immunocytochemistry, etc.) and/or hybridization
assays to detect expression of mRNAs (e.g., Northern assays, dot
blots, in situ hybridization, and the like).
[0306] Prophylactic Methods
[0307] In one aspect, the invention provides a method for
preventing, in a subject, a disease or condition associated with an
aberrant NOVX expression or activity, by administering to the
subject an agent that modulates NOVX expression or at least one
NOVX activity. Subjects at risk for a disease that is caused or
contributed to by aberrant NOVX expression or activity can be
identified by, for example, any or a combination of diagnostic or
prognostic assays as described herein. Administration of a
prophylactic agent can occur prior to the manifestation of symptoms
characteristic of the NOVX aberrancy, such that a disease or
disorder is prevented or, alternatively, delayed in its
progression. Depending upon the type of NOVX aberrancy, for
example, A NOVX agonist or NOVX antagonist agent can be used for
treating the subject. The appropriate agent can be determined based
on screening assays described herein. The prophylactic methods of
the invention are further discussed in the following
subsections.
[0308] Therapeutic Methods
[0309] Another aspect of the invention pertains to methods of
modulating NOVX expression or activity for therapeutic purposes.
The modulatory method of the invention involves contacting a cell
with an agent that modulates one or more of the activities of NOVX
protein activity associated with the cell. An agent that modulates
NOVX protein activity can be an agent as described herein, such as
a nucleic acid or a protein, a naturally-occurring cognate ligand
of A NOVX protein, a peptide, A NOVX peptidomimetic, or other small
molecule. In one embodiment, the agent stimulates one or more NOVX
protein activity. Examples of such stimulatory agents include
active NOVX protein and a nucleic acid molecule encoding NOVX that
has been introduced into the cell. In another embodiment, the agent
inhibits one or more NOVX protein activity. Examples of such
inhibitory agents include antisense NOVX nucleic acid molecules and
anti-NOVX antibodies. These modulatory methods can be performed in
vitro (e.g., by culturing the cell with the agent) or,
alternatively, in vivo (e.g., by administering the agent to a
subject). As such, the invention provides methods of treating an
individual afflicted with a disease or disorder characterized by
aberrant expression or activity of A NOVX protein or nucleic acid
molecule. In one embodiment, the method involves administering an
agent (e.g., an agent identified by a screening assay described
herein), or combination of agents that modulates (e.g.,
up-regulates or down-regulates) NOVX expression or activity. In
another embodiment, the method involves administering A NOVX
protein or nucleic acid molecule as therapy to compensate for
reduced or aberrant NOVX expression or activity.
[0310] Stimulation of NOVX activity is desirable in situations in
which NOVX is abnormally downregulated and/or in which increased
NOVX activity is likely to have a beneficial effect. One example of
such a situation is where a subject has a disorder characterized by
aberrant cell proliferation and/or differentiation (e.g., cancer or
immune associated disorders). Another example of such a situation
is where the subject has a gestational disease (e.g.,
preclampsia).
[0311] Determination of the Biological Effect of the
Therapeutic
[0312] In various embodiments of the invention, suitable in vitro
or in vivo assays are performed to determine the effect of a
specific Therapeutic and whether its administration is indicated
for treatment of the affected tissue.
[0313] In various specific embodiments, in vitro assays may be
performed with representative cells of the type(s) involved in the
patient's disorder, to determine if a given Therapeutic exerts the
desired effect upon the cell type(s). Compounds for use in therapy
may be tested in suitable animal model systems including, but not
limited to rats, mice, chicken, cows, monkeys, rabbits, and the
like, prior to testing in human subjects. Similarly, for in vivo
testing, any of the animal model system known in the art may be
used prior to administration to human subjects.
[0314] Prophylactic and Therapeutic Uses of the Compositions of the
Invention
[0315] The NOVX nucleic acids and proteins of the invention are
useful in potential prophylactic and therapeutic applications
implicated in a variety of disorders including, but not limited to:
metabolic disorders, diabetes, obesity, infectious disease,
anorexia, cancer-associated cancer, neurodegenerative disorders,
Alzheimer's Disease, Parkinson's Disorder, immune disorders,
hematopoietic disorders, and the various dyslipidemias, metabolic
disturbances associated with obesity, the metabolic syndrome X and
wasting disorders associated with chronic diseases and various
cancers.
[0316] As an example, a cDNA encoding the NOVX protein of the
invention may be useful in gene therapy, and the protein may be
useful when administered to a subject in need thereof. By way of
non-limiting example, the compositions of the invention will have
efficacy for treatment of patients suffering from: metabolic
disorders, diabetes, obesity, infectious disease, anorexia,
cancer-associated cachexia, cancer, neurodegenerative disorders,
Alzheimer's Disease, Parkinson's Disorder, immune disorders,
hematopoietic disorders, and the various dyslipidemias.
[0317] Both the novel nucleic acid encoding the NOVX protein, and
the NOVX protein of the invention, or fragments thereof, may also
be useful in diagnostic applications, wherein the presence or
amount of the nucleic acid or the protein are to be assessed. A
further use could be as an anti-bacterial molecule (i.e., some
peptides have been found to possess anti-bacterial properties).
These materials are further useful in the generation of antibodies,
which immunospecifically-bind to the novel substances of the
invention for use in therapeutic or diagnostic methods.
[0318] The invention will be further described in the following
examples, which do not limit the scope of the invention described
in the claims.
EXAMPLES
Example A
Polynucleotide And Polypeptide Sequences, And Homology Data
Example 1
[0319] The NOV1 clone was analyzed, and the nucleotide and encoded
polypeptide sequences are shown in Table 1A. TABLE-US-00002 TABLE
1A NOV1 Sequence Analysis SEQ ID NO: 1 1239 bp NOV1a,
AACCAGGGCCTTATCCAGGGCCACGCTTACAGAACTCCCACGGACACACCATGATTAG
CG100488-01
GACCCTGCTGCTGTCCACTTTGGTGGCCCTCAGTTGTGGGGTCTCCACTTACGCGCCT DNA
GATATGTCTAGGATGCTTGGAGGTGAAGAAGCGAGGCCCAACAGCTGGCCCTGGCAGG Sequence
TGAGTCTGCAGTACAGCTCCAATGGCCAGTGGTACCACACCTGCGGAGGGTCCCTGAT
AGCCAACAGCTGGGTCCTGACGGCTGCCCACTGCATCAGCTCCTCCGGGATCTACCGC
GTGATGCTGGGCCAGCATAACCTCTACGTTGCAGAGTCCGGCTCGCTGGCCGTCAGTG
TCTCTAAGATTGTGGTGCACAAGGACTGGAACTCCGACCAGGTCTCCAAAGGGAACGA
CATTGCCCTGCTCAAACTGGCTAACCCCGTCTCCCTCACCGACAAGATCCAGCTGGCC
TGCCTCCCTCCTGCCGGCACCATTCTACCCAACAACTACCCCTGCTACGTCACGGGCT
GGGGAAGGCTGCAGAGTAACGGGGCTCTCCCTGATGACCTGAAGCAGGGCCAGTTGCT
GGTTGTGGACTATGCCACCTGCTCCAGCTCTGGCTGGTGGGGCAGCACCGTGAAGACG
AATATGATCTGTGCTGGGGGTGATGGCGTGATATGCACCTGCAACGGAGACTCCGGTG
GGCCGCTGAACTGTCAGGCATCTGACGGCCGGTGGGAGGTGCATGGCATCGGCAGCCT
CACGTCGGTCCTTGGTTGCAACTACTACTACAAGCCCTCCATCTTCACGCGGGTCTCC
AACTACAACGACTGGATCAATTCGGTAAGAACCGGAGCAGCCCTGAGCCCCAAGGCAC
TGACCTGCTCACCTGGCCTCGGGAGTGCCATGCCCACCTGGCGACTGAGAACCCCCTC
CTTCCTCTTGAGAGCTAGATGGGAACCCCTTGGAGGAGGCTGCAGACCTTGGCAACTG
CTGAGTCCCCCATGGGTCCCCAAAATTTCTGTGTGGGTAAAGCTGAGTGAAAAGGAAC
ATGAGAGTATGGCCTTGTCCAAAGACGTTGGACACTCCTCAGGTACGTTAAGAGTGAG
TTCCACAGGAATGATTTTATTTTTGTGTATTTGTGTGTGGCCCAGACTCTACCATCCA
GTGCTATAAATGGGTATATGTCTGCAAAACCCAAAACCTGATACTTTGAGACCCCCAT
AGCATTAATTATTGGAAATTA ORF Start: ATG at 51 ORF Stop: TAA at 1167
SEQ ID NO: 2 372 aa MW at 40287.8kD NOV1a,
MIRTLLLSTLVALSCGVSTYAPDMSRMLGGEEARPNSWPWQVSLQYSSNGQWYRTCGG
CG100488-01
SLIANSWVLTAAHCISSSGIYRVMLGQHNLYVAESGSLAVSVSKIVVHKDWNSDQVSK Protein
GNDIALLKLANFVSLTDKIQLACLPPAGTILPNNYPCYVTGWGRLQSNGALPDDLKQG Sequence
QLLVVDYATCSSSGWWGSTVKTNMICAGGDGVICTCNGDSGGPLNCQASDGRWEVHGI
GSLTSVLGCNYYYKPSIFTRVSNYNDWINSVRTGAALSPKALTCSPGLGSAMPTWRLR
TPSFLLRARWEPLGGGCRPWQLLSPPWVPKISVWVKLSEKEHESMALSKDVGHSSGTL
RVSSTGMILFLCICVWPRLYHPVL SEQ ID NO: 3 1188 bp NOV1b,
ATGATTAGGACCCTGCTGCTGTCCACTTTGGTGGCTGGAGCCCTCAGTTGTGGGGTCT
CG100488-06
CCACTTACGCGCCTGATATGTCTAGGATGCTTGGAGGTGAAGAAGCGAGGCCCAACAG DNA
CTGGCCCTGGCAGGTGAGTCTGCAGTACAGCTCCAATGGCCAGTGGTACCACACCTGC Sequence
GGAGGGTCCCTGATAGCCAACAGCTGGGTCCTGACGGCTGCCCACTGCATCAGCTCCT
CCGGGATCTACCGCGTGATGCTGGGCCAGCATAACCTCTACGTTGCAGAGTCCGGCTC
GCTGGCCGTCAGTGTCTCTAAGATTGTGGTGCACAAGGACTGGAACTCCGACCAGGTC
TCCAAAGGGAACGACATTGCCCTGCTCAAACTGGCTAACCCCGTCTCCCTCACCGACA
AGATCCAGCTGGCCTGCCTCCCTCCTGCCGGCACCATTCTACCCAACAACTAGCCCTG
CTACGTCACGGGCTGGGGAAGGCTGCAGACCAACGGGGCTCTCCCTGATGACCTGAAG
CAGGGCCAGTTGCTGGTTGTGGACTATGCCACCTGCTCCAGCTCTGGCTGGTGGGGCA
GCACCGTGAAGACGAATATGATCTGTGCTGGGGGTAATGGCGTGATATGCACCTGCAA
CGGAGACTCTGGCGGGCCACTGAACTGTCAGGCGTCTGACGGCCGGTGGCAGGTGCAC
GGCATCGTCAGCTTCGGGTCTCGCCTCGGCTGCAACTACTACCACAAGCCCTCCGTCT
TCACGCGGGTCTCCAATTACATCGACTGGATCAATTCGGTAAGAACCGGACCAGCCTT
GAGCCCCAAGGCACTACCCTGCTCACCTGGCCTCGGGAGTGCCATGCCCACCTGGTGA
CTGAGAATCCCCTCCTTCCTCTTGAGAGCTAGATGGGAACCCCTTGGAGGAGGCTGCA
GACCTGAGTAACTGCTGGGCCTGCCATGGGTCCCCCAAATTTCTGTGTGGATAAAGCT
GAGTGAAAAGGAACATAGAGGGTGGCCTTGTCCAAAGAGGTTGGACACTCCTCAGGCA
TATGAAGAGTGAGTTCCGCTGGGCGCCGTGGCTCATGCCTGTAATCCCAGCTCTTTGG
GAGGCCAAGGCGGGCAGATCACGAGGTCAGAAGTTCAAGACCAGCCTGACCAACCTGG
CAAAACCCCATGTCTACTAAAAAAATCC ORF Start: ATG at 1 ORF Stop: TGA at
868 SEQ ID NO: 4 289 aa MW at 30820.8kD NOV1b,
MIRTLLLSTLVAGALSCGVSTYAPDMSRMLGGEEARPNSWPWQVSLQYSSNGQWYHTC
CG100488-06
GGSLIANSWVLTAAHCISSSGIYRVMLGQHNLYVAESGSLAVSVSKIVVHKDWNSDQV Protein
SKGNDIALLKLANPVSLTDKIQLACLPPAGTILPNNYPCYVTGWGRLQTNGALPDDLK Sequence
QGQLLVVDYATCSSSGWWGSTVKTNMICAGGNGVICTCNGDSGGPLNCQASDGRWQVH
GIVSFGSRLGCNYYHKPSVFTRVSNYIDWINSVRTGPALSPKALPCSPGLGSAMPTW SEQ ID
NO: 5 889 bp NOV1c,
ATGATTAGGACCCTGCTGCTGTCCACTTTGGTGGCTGGAGCCCTCAGTTGTGGGGTCT
CG100488-07
CCACTTACGCGCCTGATATGTCTAGGATGCTTGGAGGTGAAGAAGCGAGGCCCAACAG DNA
CTGGCCCTGGCAGGTGAGTCTGCAGTACAGCTCCAATGGCCAGTGGTACCACACCTGC Sequence
GGAGGGTCCCTGATAGCCAACAGCTGGGTCCTGACGGCTGCCCACTGCATCAGCTCCT
CCGGGATCTACCGCGTGATGCTGGGCCAGCATAACCTCTACGTTGCAGAGTCCGGCTC
GCTGGCCGTCAGTGTCTCTAAGATTGTGGTGCACAAGGACTGGAACTCCGACCAGGTC
TCCAAAGGGAACGACATTGCCCTGCTCAAACTGGCTAACCCCGTCTCCCTCACCGACA
AGATCCAGCTGGCCTGCCTCCCTCCTGCCGGCACCATTCTACCCAACAACTACCCCTG
CTACGTCACGGGCTGGGGAAGGCTGCAGACCAACGGGGCTCTCCCTGATGACCTGAAG
CAGGGCCAGTTGCTGGTTGTGGACTATGCCACCTGCTCCAGCTCTGGCTGGTGGGGCA
GCACCGTGAAGACGAATATGATCTGTGCTGGGGGTAATGGCGTGATATGCACCTGCAA
CGGAGACTCTGGCGGGCCACTGAACTGTCAGGCGTCTGACGGCCGGTGGCAGGTGCAC
GGCATCGTCAGCTTCGGGTCTCGCCTCGGCTGCAACTACTACCACAAGCCCTCCGTCT
TCACGCGGGTCTCCAATTACATCGACTGGATGATTGCAAATAACTAACCAAAAGAAGT
CCCTGGGACTGTTTCAGACTTGGAAAGGTCACGGAAGGAAAATAATATAATAAAGTGG
CAACTATGCAAAAAAAAAA ORF Start: ATG at 1 ORF Stop: TAA at 799 SEQ ID
NO: 6 266 aa MW at 28573.2kD NOV1c,
MIRTLLLSTLVAGALSCGVSTYAPDMSRNLGGEEARPNSWPWQVSLQYSSNGQWYHTC
CG100488-07
GGSLIANSWVLTAAHCISSSGIYRVMLGQHNLYVAESGSLAVSVSKIVVHKDWNSDQV Protein
SKGNDIALLKLANPVSLTDKIQLACLPPAGTILPNNYPCYVTGWGRLQTNGALPDDLK Sequence
QGQLLVVDYATCSSSGWWGSTVKTNMICAGGNGVICTCNGDSGGPLNCQASDGRWQVH
GIVSFGSRLGCNYYHKPSVFTRVSNYIDWMIANN SEQ ID NO: 7 1188 bp NOV1d,
ATGATTAGGACCCTGCTGCTGTCCACTTTGGTGGCTGGAGCCCTCAGTTGTGGGGACC
CG100488-08
CCACTTACCCACCTTATGTGACTAGGGTGGTTGGCGGTGAAGAAGCGAGGCCCAACAG DNA
CTGGCCCTGGCAGGTGAGTCTGCAGTACAGCTCCAATGGCCAGTGGTACCACACCTGC Sequence
GGAGGGTCCCTGATAGCCAACAGCTGGGTCCTGACGGCTGCCCACTGCATCAGCTCCT
CCGGGATCTACCGCGTGATGCTGGGCCAGCATAACCTCTACGTTGCAGAGTCCGGCTC
GCTGGCCGTCAGTGTCTCTAAGATTGTGGTGCACAAGGACTGGAACTCCGACCAGGTC
TCCAAAGGGAACGACATTGCCCTGCTCAAACTGGCTAACCCCGTCTCCCTCACCGACA
AGATCCAGCTGGCCTGCCTCCCTCCTGCCGGCACCATTCTACCCAACAACTACCCCTG
CTACGTCACGGGCTGGGGAAGGCTGCAGGCCAACGGGGCTCTCCCTGATGACCTGAAG
CAGGGCCAGTTGCTGGTTGTGGACTATGCCACCTGCTCCAGCTCTGGCTGGTGGGGCA
GCACCGTGAAGACGAATATGATCTGTGCTGGGGGTAATGGCGTGATATGCACCTGCAA
CGGAGACTCTGGCGGGCCACTGAACTGTCAGGCGTCTGACGGCCGGTGGCAGGTGCAC
GGCATCGTCAGCTTCGGGTCTCGCCTCGGCTGCAACTACTACCACAAGCCCTCCGTCT
TCACGCGGGTCTCCAATTACATCGACTGGATCAATTCGGTAAGAACCGGACCAGCCTT
GAGCCCCAAGGCACTACCCTGCTCACCTGGCCTCGGGAGTGCCATGCCCACCTGGTGA
CTGAGAATCCCCTCCTTCCTCTTGAGAGCTAGATGGGAACCCCTTGGAGGAGGCTGCA
GACCTGAGTAACTGCTGGGCCTGCCATGGGTCCCCCAAATTTCTGTGTGGATAAAGCT
GAGTGAAAAGGAACATAGAGGGTGGCCTTGTCCAAAGAGGTTGGACACTCCTCAGGCA
TATGAAGAGTGAGTTCCGCTGGGCGCCGTGGCTCATGCCTGTAATCCCAGCTCTTTGG
GAGGCCAAGGCGGGCAGATCACGAGGTCAGAAGTTCAAGACCAGCCTGACCAACCTGG
CAAAACCCCATGTCTACTAAAAAAATCC ORF Start: ATG at 1 ORF Stop: TGA at
868 SEQ ID NO: 8 289 aa MW at 30826.8kD NOV1d,
MIRTLLLSTLVAGALSCGDPTYPPYVTRVVGGEEARPNSWPWQVSLQYSSNGQWYHTC
CG100488-08
GGSLIANSWVLTAAHCISSSGIYRVMLGQHNLYVAESGSLAVSVSKIVVHKDWNSDQV Protein
SKGNDIALLKLANPVSLTDKIQLACLPPAGTILPNNYPCYVTGWGRLQANGALPDDLK Sequence
QGQLLVVDYATCSSSGWWGSTVKTNMICAGGNGVICTCNGDSGGPLNCQASDGRWQVH
GIVSFGSRLGCNYYHKFSVFTRVSNYIDWINSVRTGPALSPKALPCSPGLGSANPTW SEQ ID
NO: 9 889 bp NOV1e,
ATGATTAGGACCCTGCTGCTGTCCACTTTGGTGGCTGGAGCCCTCAGTTGTGGGGACC
CG100488-09
CCACTTACCCACCTTATGTGACTAGGGTGGTTGGCGGTGAAGAAGCGAGGCCCAACAG DNA
CTGGCCCTGGCAGGTGAGTCTGCAGTACAGCTCCAATGGCCAGTGGTACCACACCTGC Sequence
GGAGGGTCCCTGATAGCCAACAGCTGGGTCCTGACGGCTGCCCACTGCATCAGCTCCT
CCGGGATCTACCGCGTGATGCTGGGCCAGCATAACCTCTACGTTGCAGAGTCCGGCTC
GCTGGCCGTCAGTGTCTCTAAGATTGTGGTGCACAAGGACTGGAACTCCGACCAGGTC
TCCAAAGGGAACGACATTGCCCTGCTCAAACTGGCTAACCCCGTCTCCCTCACCGACA
AGATCCAGCTGGCCTGCCTCCCTCCTGCCGGCACCATTCTACCCAACAACTACCCCTG
CTACGTCACGGGCTGGGGAAGGCTGCAGGCCAACGGGGCTCTCCCTGATGACCTGAAG
CAGGGCCAGTTGCTGGTTGTGGACTATGCCACCTGCTCCAGCTCTGGCTGGTGGGGCA
GCACCGTGAAGACGAATATGATCTGTGCTGGGGGTAATGGCGTGATATGCACCTGCAA
CGGAGACTCTGGCGGGCCACTGAACTGTCAGGCGTCTGACGGCCGGTGGCAGGTGCAC
GGCATCGTCAGCTTCGGGTCTCGCCTCGGCTGCAACTACTACCACAAGCCCTCCGTCT
TCACGCGGGTCTCCAATTACATCGACTGGATGATTGCAAATAACTAACCAAAAGAAGT
CCCTGGGACTGTTTCAGACTTGGAAAGGTCACGGAAGGAAAATAATATAATAAAGTGG
CAACTATGCAAAAAAAAAA ORF Start: ATG at 1 ORF Stop: TAA at 799 SEQ ID
NO: 10 1266 aa MW at 28579.2kD NOV1e,
MIRTLLLSTLVAGALSCGDFTYPPYVTRVVGGEEARPNSWPWQVSLQYSSNGQWYHTC
CG100488-09
GGSLIANSWVLTAAHCISSSGIYRVMLGQHNLYVAESGSLAVSVSKIVVHKDWNSDQV Protein
SKGNDIALLKLANPVSLTDKIQLACLPPAGTILPNNYFCYVTGWGRLQANGALPDDLK Sequence
QGQLLVVDYATCSSSGWWGSTVKTNMICAGGNGVICTCNGDSGGFLNCQASDGRWQVH
GIVSFGSRLGCNYYHKPSVFTRVSNYIDWMIANN SEQ ID NO: 11 1080 bp NOV1f
GGATCCGTCTCCACTTACGCGCCTGATATGTCTAGGATGCTTGGAGGTGAAGAAGCGA
198353297
GGCCCAACAGCTGGCCCTGGCAGATCTCCCTGCAGTACAGCTCCAATGGCCAGTGGTA DNA
CCACACCTGCGGAGGGTCCCTGATAGCCAACAGCTGGGTCCTGACGGCTGCCCACTGC Sequence
ATCAGCTCCTCCGGGATCTACCGCGTGATGCTGGGCCAGCATAACCTCTACGTTGCAG
AGTCCGGCTCGCTGGCCGTCAGTGTCTCTAAGATTGTGGTGCACAAGGACTGGAACTC
CGACCAGGTCTCCAAAGGGAACGACATTGCCCTGCTCAAACTGGCTAACCCCGTCTCC
CTCGCCGACAAGATCCAGCTGGCCTGCCTCCCTCCTGCCGGCACCATTCTACCCAACA
ACTACCCCTGCTACGTCACGGGCTGGGGAAGGCTGCAGACCAACGGGGCTCTCCCTGA
TGACCTGAAGCAGGGCCGGTTGCTGGTTGTGGACTATGCCACCTGCTCCAGCTCTGGC
TGGTGGGGCAGCACCGTGAAGACGAATATGATCTGTGCTGGGGGTGATGGCGTGATAT
GCACCTGCAACGGAGACTCCGGTGGGCCGCTGAACTGTCAGGCATCTGACGGCCGGTG
GGAGGTGCATGGCATCGGCAGCCTCACGTCGGTCCTTGGTTGCAACTACTACTACAAG
CCCTCCATCTTCACGCGGGTCTCCAACTACAACGACTGGATCAATTCGGTAAGAACCG
GAGCAGCCCTGAGCCCCAAGGCACTGACCTGCTCACCTGGCCTCGGGAGTGCCATGCC
CACCTGGCGACTGAGAACCCCCTCCTTCCTCTTGAGAGCTAGATGGGAACCCCTTGGA
GGAGGCTGCAGACCTTGGCAACTGCTGAGTCCCCCATGGGTCCCCAAAATTTCTGTGT
GGGTAAAGCTGAGTGAAAAGGAACATGAGAGTATGGCCTTGTCCAAAGACGTTGGACA
CTCCTCAGGTACGTTAAGAGTGAGTTCCACAGGAATGATTTTATTTTTGTGTATTTGT
GTGTGGCCCAGACTCTACCATCCAGTGCTACTCGAG ORF Start: at 1 ORF Stop: end
of sequence SEQ ID NO: 12 360 aa MW at 39027.2kD NOV1f,
GSVSTYAPDMSRNLGGEEARPNSWPWQISLQYSSNGQWYHTCGGSLIANSWVLTAAHC
198353297
ISSSGIYRVMLGQHNLYVAESGSLAVSVSKIVVHKDWNSDQVSKGNDIALLKLANPVS Protein
LADKIQLACLPPAGTILPNNYPCYVTGWGRLQTNGALPDDLKQGRLLVVDYATCSSSG Sequence
WWGSTVKTNMICAGGDGVICTCNGDSGGPLNCQASDGRWEVHGIGSLTSVLGCNYYYK
PSIFTRVSNYNDWINSVRTGAALSPKALTCSPGLGSAMPTWRLRTPSFLLRARWEPLG
GGCRPWQLLSPFWVPKISVWVKLSEKEHESMALSKDVGHSSGTLRVSSTGMILFLCIC
VWPRLYHPVLLE SEQ ID NO: 13 1080 bp NOV1g,
GGATCCGTCTCCACTTACGCGCCTGATATGTCTAGGATGCGTGGAGGTGAAGAAGCGA
198353301
GGCCCAACAGCTGGCCCTGGCAGGTCTCCCTGCAGTACAGCTCCAATGGCCAGTGGTA DNA
CCACACCTGCGGAGGGTCCCTGATAGCCAACAGCTGGGTCCTGACGGCTGCCCACTGC Sequence
ATCAGCTCCTCCGGGATCTACCGCGTGATGCTGGGCCAGCATAACCTCTACGTTGCAG
AGTCCGGCTCGCTGGCCGTCAGTGTCTCTAAGATTGTGGTGCACAAGGACTGGAACTC
CGACCAGGTCTCCAAAGGGAACGACATTGCCCTGCTCAAACTGGCTAACCCCGTCTCC
CTCACCGACAAGATCCAGCTGGCCTGCCTCCCTCCTGCCGGCACCATTCTACCCAACA
ACTACCCCTGCTACGTCACGGGCTGGGGAAGGCTGCAGACCAACGGGGCTCTCCCTGA
TGACCTGAAGCAGGGCCGGTTGCTGGTTGTGGACTATGCCACCTGCTCCAGCTCTGGC
TGGTGGGGCAGCACCGTGAAGACGAATATGATCTGTGCTGGGGGTGATGGCGTGATAT
GCACCTGCAACGGAGACTCCGGTGGGCCGCTGAACTGCCAGGCATCTGACGGCCGGTG
GGAGGTGCATGGCATCGGCAGCCTCACGTCGGTCCTTGGTTGCAACTACTACTACAAG
CCCTCCATCTTCACGCGGGTCTCCAACTACAACGACTGGATCAATTCGGTAAGAACCG
GAGCAGCCCTGAGTCCCAAGGCACTGCCCTGCTCACCTGGCCTCGGGAGTGCCATGCC
CACCTGGCGACTGAGAACCCCCTCCTTCCTCTTGAGAGCTAGATGGGAACCCCTTGGA
GGAGGCTGCAGACCTTGGCAACTGCTGAGTCCCCCATGGGTCCCCAAAATTTCTGTGT
GGGTAAAGCTGAGTGAAAAGGAACATGAGAGTATGGCCTTGTCCAAAGACGTTGGACA
CTCCTCAGGTATGTTAAGAGTGAGTTCCACAGGAATGATTTTATTTTTGTGTATTTGT
GAATGGCCCAGACTCTACCATCCAGTGCTACTCGAG ORF Start: at 1 ORF Stop: end
of sequence SEQ ID NO: 14 360 aa MW at 39142.3kD NOV1g,
GSVSTYAPDMSRMRGGEEARFNSWPWQVSLQYSSNGQWYHTCGGSLIANSWVLTAAHC
198353301
ISSSGIYRVMLGQHNLYVAESGSLAVSVSKIVVHKDWNSDQVSKGNDIALLKLANPVS Protein
LTDKIQLACLPPAGTILFNNYPCYVTGWGRLQTNGALPDDLKQGRLLVVDYATCSSSG Sequence
WWGSTVKTNMICAGGDGVICTCNGDSGGPLNCQASDGRWEVHGIGSLTSVLGCNYYYK
PSIFTRVSNYNDWINSVRTGAALSPKALPCSPGLGSANPTWRLRTPSFLLRARWEPLG
GGCRPWQLLSPPWVPKISVWVKLSEKEHESMALSKDVGHSSGMLRVSSTGMILFLCIC
EWFRLYHPVLLE SEQ ID NO: 15 1080 bp NOV1h,
GGATCCGTCTCCACTTACGCGCCTGATATGTCTAGGATGCTTGGAGGTGAAGAAGCGA
198353319
GGCCCAACAGCTGGCCCTGGCAGGTCTCCCTGCAGTACAGCTCCAATGGCCAGTGGTA DNA
CCACACCTGCGGAGGGTCCCTGATAGCCAACAGCTGGGTCCTGACGGCTGCCCACTGC Sequence
ATCAGCTCCTCCAGGATCTACCGCGTGATGCTGGGCCAGCATAACCTCTACGTTGCAG
AGTCCGGCTCGCTAGCCGTCAGTGTCTCTAAGATTGTGGTGCACAAGGACTGGAACTC
CAACCAGGTCTCCAAAGGGAACGACATTGCCCTGCTCAAACTGGCTAACCCCGTCTCC
CTCACCGACAAGATCCAGCTGGCCTGCCTCCCTCCTGCCGGCACCATTCTACCCAACA
ACTACCCCTGCTACGTCACAGGCTGGGGAAGGCTGCAGACCAACGGGGCTCTCCCTGA
TGACCTGAAGCAGGGCCGGTTGCTGGTTGTGGACTATGCCACCTGCTCCAGCTCTGGC
TGGTGGGGCAGCACCGTGAAGACGAATATGATTTGTGCTGGGGGTGATGGCGTGATAT
GCACCTGCAACGGAGACTCCGGTGGGCCGCTGAACTGTCAGGCATCTGACGGCCGGTG
GGAGGTGCATGGCATCGGCAGCCTCACGTCGGTCCTTGGTTGCAACTACTACTACAAG
CCCTCCATCTTCACGCGGGTCTCCAACTACAACGACTGGATCAATTCGGTAAGAACCG
GAGCAGCCCTGAGCCCCAAGGCACTGACCTGCTCACCTGGCCTCGGGAGTGCCATGCC
CACCTGGCGACTGAGAACCCCCTCCTTCCTCTTGAGAGCTAGATGGGAACCCCTTGGA
GGAGGCTGCAGACCTTGGCAACTGCTGAGTCCCCCATGGGTCCCCAAAATTTCTGTGT
GGGTAAAGCTGAGTGAAAAGGAACATGAGAGTATGGCCTTGTCCAAAGACGTTGGACA
CTCCTCAGGTATGTTAAGAGTGAGTTCCACAGGAATGATTTTATTTTTGTGTATTTGT
GTGTGGCCCAGACTCTACCATCCAGTGCTACTCGAG ORF Start: at 1 ORF Stop: end
of sequence SEQ ID NO: 16 360 aa MW at 39171.4kD NOV1h,
GSVSTYAPDMSRNLGGEEARPNSWPWQVSLQYSSNGQWYHTCGGSLIANSWVLTAAHC
198353319
ISSSRIYRVMLGQHNLYVAESGSLAVSVSKIVVHKDWNSNQVSKGNDIALLKLANPVS Protein
LTDKIQLACLPPAGTILFNNYPCYVTGWGRLQTNGALFDDLKQGRLLVVDYATCSSSG Sequence
WWGSTVKTNMICAGGDGVICTCNGDSGGPLNCQASDGRWEVHGIGSLTSVLGCNYYYK
PSIFTRVSNYNDWINSVRTGAALSPKALTCSPGLGSAMPTWRLRTPSFLLRARWEFLG
GGCRPWQLLSPPWVFKISVWVKLSEKEHESMALSKDVGHSSGMLRVSSTGMILFLCIC
VWPRLYHPVLLE SEQ ID NO: 17 1081 bp NOV1i,
GGATCCGTCTCCACTTACGCGCCTGATATGTCTAGGATGCTTGGAGGTGAAGAAGCGA
198362547
GGCCCAACAGCTGGCCCTGGCAGGTCTCCCTGCAGTACAGCTCCAATGGCCAGTGGTA DNA
CCAGACCTGCGGAGGGTCCCTGATAGCCAACAGCTGGGTCCTGACGGCTGCCCACTGC Sequence
ATCAGCTCCTCCGGGATCTACCGCGTGATGCTGGGCCAGCATAACCTCTACGTTGCAG
AGTCCGGCTCGCTGGCCGTCAGTGTCTCTAAGATTGTGGTGCACAAGGACTGGAACTC
CGACCAGGTCTCCAAAGGGAACGACATTGCCCTGCTCAAACTGGCTAACCCCGTCTCC
CTCACCGACAAGATCCAGCTGGCCTGCCTCCCTCCTGCCGGCACCATTCTACCCAACA
ACTACCCCTGCTACGTCACGGGCTGGGGAAGGCTGCAGACCAACGGGGCTCTCCCTGA
TGACCTGAAGCAGGGCCGGTTGCTGGTTGTGGACTATGCCACCTGCTCCAGCTCTGGC
TGGTGGGGCAGCACCGTGAAGACGAATATGATCTGTGCTGGGGGTGATGGCGTGATAT
GCACCTGCAACGGAGACTCCGGTGGGCCGCTGAACTGTCAGGCATCTGACGGCCGGTG
GGAGGTGCATGGCATCGGCAGCCTCACGTCGGTCCTTGGTTGCAACTACTACTACAAG
CCCTCCATCTTCACGCGGGTCTCCAACTACAACGACTGGATCAATTCGGTAAGAACCG
GAGCAGCCCTGAGCCCCAAGGCACTGCCCTGCTCACCTGGCCTCGGGAGTGCCATGCC
CACCTGGCGACTGAGAACCCCCTCCTTCCTCTTGAGAGCTAGATGGGAACCCCTTGGA
GGAGGCTGCAGACCTTGGCAACTGCTGAGTCCCCCATGGGTCCCCAAAATTTCTGTGT
GGGTAAAGCTGAGTGAAAAGGAACATGAGAGTATGGCCTTGTCCAAAGACGTTGGACA
CTCCTCAGGTATGTTAAGAGTGAGTTCCACAGGAATGATTTTATTTTTGTGTATTTGT
GTGTGGCCCAGACTCTACCATCCAGTGCTACTCGAG ORF Start: at 1 ORF Stop: end
of sequence SEQ ID NO: 18 360 aa MW at 39069.3kD NOV1i,
GSVSTYAPDMSRNLGGEEARPNSWPWQVSLQYSSNGQWYHTCGGSLIANSWVLTAAHC
198362547
ISSSGIYRVMLGQHNLYVAESGSLAVSVSKIVVHKDWNSDQVSKGNDIALLKLANPVS Protein
LTDKIQLACLPPAGTILPNNYPCYVTGWGRLQTNGALFDDLKQGRLLVVDYATCSSSG Sequence
WWGSTVKTNMICAGGDGVICTCNGDSGGPLNCQASDGRWEVHGIGSLTSVLGCNYYYK
PSIFTRVSNYNDWINSVRTGAALSPKALPCSFGLGSANPTWRLRTPSFLLRARWEPLG
GGCRPWQLLSPPWVPKISVWVKLSEKEHESMALSKDVGHSSGMLRVSSTGMILFLCIC
VWPRLYHPVLLE SEQ ID NO: 19 1023 bp NOV1j,
GGATCCGTCTCCACTTACGCGCCTGATATGTCTAGGATGCTTGGAGGTGAAGAAGCGA
198362642
GGCCCAACAGCCGGCCCTGGCAGGTCTCCCTGCAGTACAGCTCCAATGGCCAGTGGTA DNA
CCACACCTGCGGAGGGTCCCTGATAGCCAACAGCTGGGTCCTGACGGCTGCCCACTGC Sequence
ATCAGCTCCTCCGGGATCTACCGCGTGATGCTGGGCCAGCATAACCTCTACGTTGCAG
AGTCCGGCTCGCTGGCCGTCAGTGTCTCTAAGATTGTGGTGCACAAGGACTGGAACTC
CGACCAGGTCTCCAAAGGGAACGACATTGCCCTGCTCAAACTGGCTAACCCCGTCTCC
CTCACCGACAAGATCCAGCTGGCCTGCCTCCCTCCTGCCGGCACCATTCTACCCAACA
ACTACCCCTGCTACGTCACGGGCTGGGGAAGGCTGCAGACCAACGGGGCTCTCCCTGA
TGACCTGAAGCAGGGCCGGTTGCTGGTTGTGGACTATGCCACCTGCTCCAACTCTGGC
TGGTGGGGCAGCACCGTGAAGACGAATATGATCTGTGCTGGGGGTGATGGCGTGATAT
GCACCTGCAACGGAGACTCCGGTGGGCCGCTGAACTGTCAGGCATCTGACGGCCGGTG
GGAGGTGCATGGCATCGGCAGCCTCACGTCGGTCCTTGGTTGCAACTACTACTACAAG
CCCTCCATCTTCACGCGGGTCTCCAACTACAACGACTGGATCAATTCGGTAAGAACCG
GAGCAGCCCTGAGCCCCAAGGCACTGACCTGCTCACCTGGCCTCGGGAGTGCCATGCC
CACCTGGCGACTGAGAACCCCCTCCTTCCTCTTGAGAACTAGATGGGAACCCCTTGGA
GGAGGCTGCAGACCTTGGCAACTGCTGAGTCCCCCATGGGTCCCCAAAATTTCTGTGT
GGGTAAAGCTGAGTGAAAAGGAACATGAGAGTATGGCCTTGTCCAAAGACGTTGGACA
CTCCTCAGGTACGTTAAGAGTGAGTTCCACACTCGAG ORF Start: at 1 ORF Stop: end
of sequence SEQ ID NO: 20 341 aa MW at 36814.4kD NOV1j,
GSVSTYAPDMSRMLGGEEARPNSRPWQVSLQYSSNGQWYHTCGGSLIANSWVLTAAHC
198362642
ISSSGIYRVMLGQHNLYVAESGSLAVSVSKIVVHKDWNSDQVSKGNDIALLKLANPVS Protein
LTDKIQLACLPFAGTILFNNYPCYVTGWGRLQTNGALPDDLKQGRLLVVDYATCSNSG Sequence
WWGSTVKTNMICAGGDGVICTCNGDSGGPLNCQASDGRWEVHGIGSLTSVLGCNYYYK
PSIFTRVSNYNDWINSVRTGAALSPKALTCSFGLGSAMPTWRLRTPSFLLRTRWEPLG
GGCRPWQLLSFPWVPKISVWVKLSEKEHESMALSKDVGHSSGTLRVSSTLE
[0320] Sequence comparison of the above protein sequences yields
the following sequence relationships shown in Table 1B.
TABLE-US-00003 TABLE 1B Comparison of NOV1a against NOV1b through
NOV1j. Protein NOV1a Residues/ Identities/Similarities for the
Sequence Match Residues Matched Region NOV1b 1 . . . 287 275/289
(95%) 1 . . . 289 280/289 (96%) NOV1c 1 . . . 260 249/262 (95%) 1 .
. . 262 255/262 (97%) NOV1d 1 . . . 287 267/289 (92%) 1 . . . 289
276/289 (95%) NOV1e 1 . . . 260 241/262 (91%) 1 . . . 262 251/262
(94%) NOV1f 17 . . . 372 352/356 (98%) 3 . . . 358 355/356 (98%)
NOV1g 17 . . . 372 350/356 (98%) 3 . . . 358 352/356 (98%) NOV1h 17
. . . 372 351/356 (98%) 3 . . . 358 354/356 (98%) NOV1i 17 . . .
372 352/356 (98%) 3 . . . 358 354/356 (98%) NOV1j 17 . . . 353
332/337 (98%) 3 . . . 339 335/337 (98%)
[0321] Further analysis of the NOV1a protein yielded the following
properties shown in Table 1C. TABLE-US-00004 TABLE 1C Protein
Sequence Properties NOV1a PSort 0.5469 probability located in
outside; 0.1000 probability analysis: located in endoplasmic
reticulum (membrane); 0.1000 probability located in endoplasmic
reticulum (lumen); 0.1000 probability located in lysosome (lumen)
SignalP Cleavage site between residues 17 and 18 analysis:
[0322] A search of the NOV1a protein against the Geneseq database,
a proprietary database that contains sequences published in patents
and patent publication, yielded several homologous proteins shown
in Table 1D. TABLE-US-00005 TABLE 1D Geneseq Results for NOV1a
NOV1a Identities/ Residues/ Similarities for Geneseq
Protein/Organism/Length Match the Matched Expect Identifier [Patent
#, Date] Residues Region Value AAM78338 Human protein SEQ ID NO
1000 - 1 . . . 277 261/279 (93%) e-156 homo sapiens, 1052 aa. 1 . .
. 279 268/279 (95%) [WO200157190-A2, 09-AUG- 2001] AAP70760 Human
pancreas elastase-2 - Sus 1 . . . 263 259/265 (97%) e-155 scrofa,
269 aa. [JP62000276-A, 06- 1 . . . 265 262/265 (98%) JAN-1987]
AAP60059 Sequence of human pancreatic 15 . . . 263 245/249 (98%)
e-149 elastase IIB - Homo sapiens, 253 1 . . . 249 248/249 (99%)
aa. [EP198645-A, 22-OCT-1986] AAP60062 Sequence of human pancreatic
1 . . . 263 230/265 (86%) e-137 elastase IIA encoded on pH2E2 - 1 .
. . 265 248/265 (92%) Homo sapiens, 269 aa. [EP198645- A,
22-OCT-1986] AAP61723 Human elastase II - Homo sapiens, 1 . . . 263
229/265 (86%) e-135 269 aa. [JP61192288-A, 26-AUG- 1 . . . 265
246/265 (92%) 1986]
[0323] In a BLAST search of public sequence datbases, the NOV1a
protein was found to have homology to the proteins shown in the
BLASTP data in Table 1E. TABLE-US-00006 TABLE 1E Public BLASTP
Results for NOV1a NOV1a Identities/ Protein Residues/ Similarities
for Accession Match the Matched Number Protein/Organism/Length
Residues Portion Expect Value Q96QV5 BA265F14.3 (ELASTASE 2B) - 1 .
. . 263 262/265 (98%) e-157 Homo sapiens (Human), 269 aa. 1 . . .
265 263/265 (98%) P08218 Elastase 2B precursor (EC 1 . . . 263
259/265 (97%) e-155 3.4.21.71) - Homo sapiens 1 . . . 265 262/265
(98%) (Human), 269 aa. P08217 Elastase 2A precursor (EC 1 . . . 263
230/265 (86%) e-137 3.4.21.71) - Homo sapiens 1 . . . 265 248/265
(92%) (Human), 269 aa. P08419 Elastase 2 precursor (EC 1 . . . 263
204/265 (76%) e-122 3.4.21.71) - Sus scrofa (Pig), 269 1 . . . 265
230/265 (85%) aa. Q29461 Elastase 2 precursor (EC 1 . . . 263
202/265 (76%) e-121 3.4.21.71) - Bos taurus (Bovine), 1 . . . 265
231/265 (86%) 269 aa.
[0324] PFam analysis predicts that the NOV1a protein contains the
domains shown in the Table 1F. TABLE-US-00007 TABLE 1F Domain
Analysis of NOV1a NOV1a Identities/ Match Similarities Pfam Domain
Region for the Matched Region Expect Value trypsin 27 . . . 260
120/261 (46%) 1.3e-87 192/261 (74%)
Example 2
[0325] The NOV2 clone was analyzed, and the nucleotide and encoded
polypeptide sequences are shown in Table 2A. TABLE-US-00008 TABLE
2A NOV2 Sequence Analysis SEQ ID NO: 21 1800 bp NOV2a,
GAGCCTCTCTTCACCATGTGCTTCGTCCCCCTGGTGTGCTGGGTGGTGTGTACCTGCC
CG100560-01
TCCAGCAGCAGCTGGAGGGTGGGGGGCTGTTGAGACAGACGTCCAGGACCACCACTGC DNA
AGTGTACATGCTCTACCTGCTGAGTCTGATGCAACCCAAGCCGGGGGCCCCGCGCCTC Sequence
CAGCCCCCACCCAACCAGAGAGGGTTGTGCTCCTTGGCGGCAGATGGGCTCTGGAATC
AGAAAATCCTATTTGAGGAGCAGGACCTCCGGAAGCACGGCCTAGACGGGGAAGACGT
CTCTGCCTTCCTCAACATGAACATCTTCCAGAAGGACATCAACTGTGAGAGGTACTAC
AGCTTCATCCACTTGAGTTTCCAGGAATTCTTTGCAGCTATGTACTATATCCTGGACG
AGGGGGAGGGCGGGGCAGGCCCAGACCAGGACGTGACCAGGCTGTTGACCGAGTACGC
GTTTTCTGAAAGGAGGTTCCTGGCACTCACCAGCCGCTTCCTGTTTGGACTCCTGAAC
GAGGAGACCAGGAGCCACCTGGAGAAGAGTCTCTGCTGGAAGGTCTCGCCGCACATCA
AGATGGACCTGTTGCAGTGGATCCAAAGCAAAGCTCAGAGCGACGGCTCCACCCTGCA
GCAGGGCTCCTTGGAGTTCTTCAGCTGCTTGTACGAGATCCAGGAGGAGGAGTTTATC
CAGCAGGCCCTGAGCCACTTCCAGGTGATCGTGGTCAGCAACATTGCCTCCAAGATGG
AGCACATGGTCTCCTCGTTCTGTCTGAAGCGCTGCAGGAGCGCCCAGGTGCTGCACTT
GTATGGCGCCACCTACAGCGCGGACGGGGAAGACCGCGCGAGGTGCTCCGCAGGAGCG
CACACGCTGTTGGTGCAGCTGAGACCAGAGAGGACCGTTCTGCTGGACGCCTACAGTG
AACATCTGGCAGCGGCCCTGTGCACCAATCCAAACCTGATAGAGCTGTCTCTGTACCG
AAATGCCCTGGGCAGCCGGGGGGTGAAGCTGCTCTGTCAAGGACTCAGACACCCCAAC
TGCAAACTTCAGAACCTGAGGAGGCTGAAGAGGTGCCGCATCTCCAGCTCAGCCTGCG
AGGACCTCTCTGCAGCTCTCATAGCCAATAAGAATTTGACAAGGATGGATCTCAGTGG
CAACGGCGTTGGATTCCCAGGCATGATGCTGCTTTGCGAGGGCCTGCGGCATCCCCAG
TGCAGGCTGCAGATGATTCAGTTGAGGAAGTGTCAGCTGGAGTCCGGGGCTTGTCAGG
AGATGGCTTCTGTGCTCGGCACCAACCCACATCTGGTTGAGTTGGACCTGACAGGAAA
TGCACTGGAGGATTTGGGCCTGAGGTTACTATGCCAGGGACTGAGGCACCCAGTCTGC
AGACTACGGACTTTGTGGTGCAGGCTGAAGATCTGCCGCCTCACTGCTGCTGCCTGTG
ACGAGCTGGCCTCAACTCTCAGTGTGAACCAGAGCCTGAGAGAGCTGGACCTGAGCCT
GAATGAGCTGGGGGACCTCGGGGTGCTGCTGCTGTGTGAGGGCCTCAGGCATCCCACG
TGCAAGCTCCAGACCCTGCGGAGGTTGGGCATCTGCCGGCTGGGCTCTGCCGCCTGTG
AGGGTCTTTCTGTGGTGCTCCAGGCCAACCACAACCTCCGGGAGCTGGACTTGAGTTT
CAACGACCTGGGAGACTGGGGCCTGTGGTTGCTGGCTGAGGGGCTGCAACATCCCGCC
TGCAGACTCCAGAAACTGTGGTGAGCATCGGGGAGTGACGGGGTGGCAGTGGTCACGT TT ORF
Start: ATG at 16 ORF Stop: TGA at 1762 SEQ ID NO: 22 582aa MW at
65280.8kD NOV2a,
MCFVPLVCWVVCTCLQQQLEGGGLLRQTSRTTTAVYMLYLLSLMQPKPGAPRLQPPPN
CG100560-01
QRGLCSLAADGLWNQKILFEEQDLRKHGLDGEDVSAFLNMNIFQKDINCERYYSFIHL Protein
SFQEFFAAMYYILDEGEGGAGPDQDVTRLLTEYAFSERSFLALTSRFLFGLLNEETRS Sequence
HLEKSLCWKVSPHIKMDLLQWIQSKAQSDGSTLQQGSLEFFSCLYEIQEEEFIQQALS
HFQVIVVSNIASKMEHMVSSFCLKRCRSAQVLHLYGATYSADGEDRARCSAGAHTLLV
QLRPERTVLLDAYSEHLAAALCTNPNLIELSLYRNALGSRGVKLLCQGLRHPNCKLQN
LRRLKRCRISSSACEDLSAALIANKNLTRMDLSGNGVGFPGMMLLCEGLRHPQCRLQM
IQLRKCQLESGACQEMASVLGTNPHLVELDLTGNALEDLGLRLLCQGLRHPVCRLRTL
WCRLKICRLTAAACDELASTLSVNQSLRELDLSLNELGDLGVLLLCEGLRHPTCKLQT
LRRLGICRLGSAACEGLSVVLQANHNLRELDLSFNDLGDWGLWLLAEGLQHPACRLQK LW SEQ
ID NO: 23 1683 bp NOV2b,
GCGCGCCTCTCTTCACCATGTGCTTCGTCCCCCTGGTGTGCTGGGTGGTGTGTACCTG
CG100560-02
CCTCCAGCAGCAGCTGGAGGGTGGGGGGCTGTTGAGACAGACGTCCAGGACCACCACT DNA
GCAGTGTACATGCTCTACCTGCTGAGTCTGATGCAACCCAAGCCGGGGGCCCCGCGCC Sequence
TCCAGCCCCCACCCAACCAGAGAGGGTTGTGCTCCTTGGCGGCAGATGGGCTCTGGAA
TCAGAAAATCCTATTTGAGGAGCAGGACCTCCGGAAGCACGGCCTAGACGGGGAAGAC
GTCTCTGCCTTCCTCAACATGAACATCTTCCAGAAGGACATCAACTGTGAGAGGTACT
ACAGCTTCATCCACTTGAGTTTCCAGGAATTCTTTGCAGCTATGTACTATATCCTGGA
CGAGGGGGAGGGCGGGGCAGGCCCAGACCAGGACGTGACCAGGCTGTTGACCGAGTAC
GCGTTTTCTGAAAGGAGCTTCCTGGCACTCACCAGCCGCTTCCTGTTTGGACTCCTGA
ACGAGGAGACCAGGAGCCACCTGGAGAAGAGTCTCTGCTGGAAGGTCTCGCCGCACAT
CAAGATGGACCTGTTGCAGTGGATCCAAAGCAAAGCTCAGAGCGACGGCTCCACCCTG
CAGCAGGGCTCCTTGGAGTTCTTCAGCTGCTTGTACGAGATCCAGGAGGAGGAGTTTA
TCCAGCAGGCCCTGAGCCACTTCCAGGTGATCGTGGTCAGCAACATTGCCTCCAAGAT
GGAGCACATGGTCTCCTCGTTCTGTCTGAAGCGCTGCAGGAGCGCCCAGGTGCTGCAC
TTGTATGGCGCCACCTACAGCGCGGACGGGGAAGACCGCGCGAGGTGCTCCGCAGGAG
CGCACACGCTGTTGGTGCAGCTCAGACCAGAGAGGACCGTTCTGCTGGACGCCTACAG
TGAACATCTGGCAGCGGCCCTGTGCACCAATCCAAACCTGATAGAGCTGTCTCTGTAC
CGAAATGCCCTGGGCAGCCGGGGGGTGAAGCTGCTCTGTCAAGGACTCAGACACCCCA
ACTGCAAACTTCAGAACCTGAGGCTGAAGAGGTGCCGCATCTCCAGCTCAGCCTGCGA
GGACCTCTCTGCAGCTCTCATAGCCAATAAGAATTTGACAAGGATGGATCTCAGTGGC
AACGGCGTTGGATTCCCAGGCATGATGCTGCTTTGCGAGGGCCTGCGGCATCCCCAAT
GCAGGCTGCAGATGATTCAGCTGAAGATCTGCCGCCTCACTGCTGCTGCCTGTGACGA
GCTGGCCTCAACTCTCAGTGTGAACCAGAGCCTGAGAGAGCTGGACCTGAGCCTGAAT
GAGCTGGGGGACCTCGGGGTGCTGCTGCTGTGTGAGGGCCTCAGGCATCCCACGTGCA
AGCTCCAGACCCTGCGGTTGGGCATCTGCCGGCTGGGCTCTGCCGCCTGTGAGGGTCT
TTCTGTGGTGCTCCAGGCCAACCACAACCTCCGGGAGCTGGACTTGAGTTTCAACGAC
CTGGGAGACTGGGGCCTGTGGTTGCTGGCTGAGGGGCTGCAACATCCCGCCTGCAGAC
TCCAGAAACTGTGGTGAGCATCGGGGAGTGACGGGGTGGCAGTGGTCACGTTTGGACA
GTGGAAGCGCCTTCTCATCCTTCATTTTTCTATTTATGAACTATCCTGCTTCACTACA A ORF
Start: ATG at 18 ORF Stop: TGA at 1581 SEQ ID NO: 24 521 aa MW at
58384.7kD NOV2b,
MCFVPLVCWVVCTCLQQQLEGGGLLRQTSRTTTAVYMLYLLSLMQPKPGAPRLQPPPN
CG100560-02
QRGLCSLAADGLWNQKILFEEQDLRKHGLDGEDVSAFLNMNIFQKDINCERYYSFIHL Protein
SFQEFFAAMYYILDEGEGGAGFDQDVTRLLTEYAFSERSFLALTSRFLFGLLNEETRS Sequence
HLEKSLCWKVSPHIKMDLLQWIQSKAQSDGSTLQQGSLEFFSCLYEIQEEEFIQQALS
HFQVIVVSNIASKMEHMVSSFCLKRCRSAQVLHLYGATYSADGEDRARCSAGAHTLLV
QLRPERTVLLDAYSEHLAAALCTNPNLIELSLYRNALGSRGVKLLCQGLRHPNCKLQN
LRLKRCRISSSACEDLSAALIANKNLTPNDLSGNGVGFPGMMLLCEGLRHPQCRLQMI
QLKICRLTAAACDELASTLSVNQSLRELDLSLNELGDLGVLLLCEGLRHPTCKLQTLR
LGICRLGSAACEGLSVVLQANHNLRELDLSFNDLGDWGLWLLAEGLQHPACRLQKLW
[0326] Sequence comparison of the above protein sequences yields
the following sequence relationships shown in Table 2B.
TABLE-US-00009 TABLE 2B Comparison of NOV2a against NOV2b. NOV2a
Residues/ Identities/Similarities for the Protein Sequence Match
Residues Matched Region NOV2b 1 . . . 523 450/523 (86%) 1 . . . 520
464/523 (88%)
[0327] Further analysis of the NOV2a protein yielded the following
properties shown in Table 2C. TABLE-US-00010 TABLE 2C Protein
Sequence Properties NOV2a PSort 0.3700 probability located in
outside; 0.1900 probability analysis: located in lysosome (lumen);
0.1000 probability located in endoplasmic reticulum (membrane);
0.1000 probability located in endoplasmic reticulum (lumen) SignalP
Cleavage site between residues 50 and 51 analysis:
[0328] A search of the NOV2a protein against the Geneseq database,
a proprietary database that contains sequences published in patents
and patent publication, yielded several homologous proteins shown
in Table 2D. TABLE-US-00011 TABLE 2D Geneseq Results for NOV2a
NOV2a Identities/ Residues/ Similarities for Geneseq
Protein/Organism/Length [Patent Match the Matched Expect Identifier
#, Date] Residues Region Value AAU01067 Human secreted protein
sequence 1 . . . 581 275/602 (45%) e-143 encoded by gene #28 - Homo
1 . . . 596 380/602 (62%) sapiens, 630 aa. [WO200123402- A1,
05-APR-2001] AAE07514 Human PYRIN-1 protein - Homo 1 . . . 581
275/602 (45%) e-143 sapiens, 1034 aa. [WO200161005- 406 . . . 1001
380/602 (62%) A2, 23-AUG-2001] AAU01096 Gene 28 Human secreted
protein 1 . . . 523 236/532 (44%) e-123 homologous amino acid
sequence - 1 . . . 482 324/532 (60%) Homo sapiens, 484 aa.
[WO200123402-A1, 05-APR-2001] AAY39778 CBDAKD01 protein sequence -
1 . . . 464 210/487 (43%) e-106 Homo sapiens, 514 aa. 1 . . . 481
298/487 (61%) [WO9946290-A1, 16-SEP-1999] ABG04570 Novel human
diagnostic protein 156 . . . 324 167/169 (98%) 5e-90 #4561 - Homo
sapiens, 168 aa. 1 . . . 168 167/169 (98%) [WO200175067-A2,
11-OCT-2001]
[0329] In a BLAST search of public sequence datbases, the NOV2a
protein was found to have homology to the proteins shown in the
BLASTP data in Table 2E. TABLE-US-00012 TABLE 2E Public BLASTP
Results for NOV2a NOV2a Identities/ Protein Residues/ Similarities
for Accession Match the Matched Expect Number
Protein/Organism/Length Residues Portion Value AAH28069
HYPOTHETICAL 120.2 KDA 1 . . . 582 577/582 (99%) 0.0 PROTEIN - Homo
sapiens (Human), 400 . . . 976 577/582 (99%) 1061 aa. Q96P20 Cold
autoinflammatory syndrome 1 1 . . . 581 275/602 (45%) e-143 protein
(Cryopyrin) (NACHT-, LRR- 406 . . . 1001 380/602 (62%) and
PYD-containing protein 3) (PYRIN-containing APAF1-like protein 1)
(Angiotensin/vasopressin receptor AII/AVP-like) - Homo sapiens
(Human), 1034 aa. AAL78632 NALP3 LONG ISOFORM - Homo 1 . . . 581
275/602 (45%) e-143 sapiens (Human), 1036 aa. 408 . . . 1003
379/602 (62%) AAL90874 MAST CELL MATURATION 1 . . . 581 274/603
(45%) e-140 INDUCIBLE PROTEIN 1 - Mus 404 . . . 1000 372/603 (61%)
musculus (Mouse), 1033 aa. AAL12498 CRYOPYRIN - Homo sapiens 1 . .
. 464 220/485 (45%) e-115 (Human), 920 aa. 406 . . . 887 310/485
(63%)
[0330] PFam analysis predicts that the NOV2a protein contains the
domains shown in the Table 2F. TABLE-US-00013 TABLE 2F Domain
Analysis of NOV2a Identities/ NOV2a Match Similarities for Pfam
Domain Region the Matched Region Expect Value
Example 3
[0331] The NOV3 clone was analyzed, and the nucleotide and encoded
polypeptide sequences are shown in Table 3A. TABLE-US-00014 TABLE
3A NOV3 Sequence Analysis SEQ ID NO: 25 1481 bp NOV3a,
CTTGTCTTGTTCCAGTTCTCAGAGGGAATGCTTTCAATTTTTCTCTATTCAGTATTAT
CG101012-01
GTTGGCTGTGGGTTTGTCATAGATTGTGTGCCGTGAGGGAGTTTACTTTCCTGGCCAA DNA
GAAGCCAGGCTGCAGGGGCCTTCGGATCACCACGGATGCCTGCTGGGGTCGCTGTGAG Sequence
ACCTTCTATCTATGGGGACAGAAACCCATTCTGGAACCCCCCTATATTGAAGCCCATC
ATCGAGTCTGTACCTACAACGAGACCAAACAGGTGACTGTCAAGCTGCCCAACTGTGC
CCCGGGAGTCGACCCCTTCTACACCTATCCCGTGGCCATCCGCTGTGACTGCGGAGCC
TGCTCCACTGCCACCACGGAGTGTGAGACCATCTGAGGCCGCTAGCTGCTCTCTGCAG
ACCCACCTGTGTGAGCAGCACATGCAGTTATACTTCCTGGATGCAAGACTGTTTAATT
TCGACCACACCCATGGA ORF Start: ATG at 28 ORF Stop: TGA at 382 SEQ ID
NO: 26 118 aa MW at 13491.6kD NOV3a,
MLSIFLYSVLCWLWVCHRLCAVREFTFLAKKPGCRGLRITTDACWGRCETFYLWGQKP
CG101012-01
ILEPPYIEAHHRVCTYNETKQVTVKLPNCAPGVDPFYTYPVAIRCDCGACSTATTECE Protein
TI Sequence
[0332] TABLE-US-00015 TABLE 3B Protein Sequence Properties NOV3a
PSort 0.5500 probability located in endoplasmic reticulum analysis:
(membrane); 0.1900 probability located in lysosome (lumen); 0.1449
probability located in microbody (peroxisome); 0.1000 probability
located in endoplasmic reticulum (lumen) SignalP Cleavage site
between residues 22 and 23 analysis:
[0333] A search of the NOV3a protein against the Geneseq database,
a proprietary database that contains sequences published in patents
and patent publication, yielded several homologous proteins shown
in Table 3C. TABLE-US-00016 TABLE 3C Geneseq Results for NOV3a
Identities/ NOV3a Similarities Residues/ for the Geneseq
Protein/Organism/Length [Patent Match Matched Expect Identifier #,
Date] Residues Region Value AAU10366 Human beta-like glycoprotein
20 . . . 118 93/99 (93%) 7e-53 hormone, Beta10 - Homo sapiens, 36 .
. . 130 95/99 (95%) 130 aa. [WO200173034-A2, 04- OCT-2001] AAG64065
Human anterior pituitary hormone- 20 . . . 118 93/99 (93%) 7e-53
related polypeptide #2 - Homo 12 . . . 106 95/99 (95%) sapiens, 106
aa. [WO200144475-A1, 21-JUN-2001] AAG64064 Human anterior pituitary
hormone- 20 . . . 118 93/99 (93%) 7e-53 related polypeptide - Homo
sapiens, 36 . . . 130 95/99 (95%) 130 aa. [WO200144475-A1, 21-
JUN-2001] AAG63211 Amino acid sequence of a human 20 . . . 118
93/99 (93%) 7e-53 cystine knot polypeptide - Homo 36 . . . 130
95/99 (95%) sapiens, 130 aa. [WO200153346-A1, 26-JUL-2001] AAE09440
Human sbghGTa protein - Homo 20 . . . 118 93/99 (93%) 7e-53
sapiens, 130 aa. [WO200160850-A1, 36 . . . 130 95/99 (95%)
23-AUG-2001]
[0334] In a BLAST search of public sequence datbases, the NOV3a
protein was found to have homology to the proteins shown in the
BLASTP data in Table 3D. TABLE-US-00017 TABLE 3D Public BLASTP
Results for NOV3a Identities/ NOV3a Similarities Protein Residues/
for the Accession Match Matched Expect Number
Protein/Organism/Length Residues Portion Value Q9I997
FOLLICLE-STIMULATING 2 . . . 118 49/119 (41%) 8e-20 HORMONE
PRECURSOR - 3 . . . 116 66/119 (55%) Acipenser baerii (Siberian
sturgeon), 128 aa. Q98849 Gonadotropin beta-II chain precursor 4 .
. . 115 43/117 (36%) 8e-16 (GTH-II-beta) (Luteinizing hormone- 9 .
. . 120 63/117 (53%) like GTH) - Carassius auratus (Goldfish), 140
aa. Q90ZK1 FOLLICLE STIMULATING 5 . . . 115 46/112 (41%) 2e-15
HORMONE BETA SUBUNIT 1 . . . 108 59/112 (52%) PRECURSOR - Rana
ridibunda (Laughing frog) (Marsh frog), 123 aa (fragment). P01235
Gonadotropin beta-II chain precursor 26 . . . 115 37/91 (40%) 2e-15
(GTH-II-beta) (Luteinizing hormone- 39 . . . 124 54/91 (58%) like
GTH) - Cyprinus carpio (Common carp), 144 aa. Q98TY3 LUTEINIZING
HORMONE BETA 1 . . . 115 44/118 (37%) 2e-15 SUBUNIT -
Mylopharyngodon 8 . . . 120 62/118 (52%) piceus, 140 aa.
[0335] PFam analysis predicts that the NOV3a protein contains the
domains shown in the Table 3E. TABLE-US-00018 TABLE 3E Domain
Analysis of NOV3a Identities/ NOV3a Similarities for Pfam Domain
Match Region the Matched Region Expect Value Cys_knot 29 . . . 116
36/92 (39%) 2.5e-14 62/92 (67%)
Example 4
[0336] The NOV4 clone was analyzed, and the nucleotide and encoded
polypeptide sequences are shown in Table 4A. TABLE-US-00019 TABLE
4A NOV4 Sequence Analysis SEQ ID NO: 27 682 bp NOV4a,
ATGAAGACCCTGTTCCTGGGTGTCACGCTCGGCCTGGCCGCTGCCCTGTCCTTCACCC
CG101584-01
TGGAGGAGGAGGATGTGCATCCAGAAGAAAATCCTGATGCGGAATGGGGGCAGGAAGC DNA
TCATGTACCTGCAGGAGCTGCCCAGGAGGGACCACTACATCTTTTACTGCAAAGACCA Sequence
GCACCATGGGGGCCTGCTCCACATGGGAAAGCTTGTGGGTGCTCCCTGCAGGGCCGTG
CCGCTGTCCCCACGTCGGCTCACCTGGCCACCTCACCTGCAGGTAGGAATTCTGATAC
CAACCGGGAGGCCCTGGAAGAATTTAAGAAATTGGTGCAGCGCAAGGGACTCTCGGAG
GAGGACATTTTCACGCCCCTGCAGACGGGTGAGGATGGCTGTGCCCAGTCCCCTGTGT
CCCTCTGCTGTGTCTGTCTGCTATCTCCAGTGTCCCATGACCCCCATGTCCTCCCATG
TCCCCCGCATTCCCCATGTGCCCCGAGTCTCCTCGCAGGGGCTCCCGGGCCCTGTTTA
GCGTCCTCCTCATTGGAGGCTCTGTGCTCTGGGCTGCGATGGGGTCTGGGGCTCCGCG
CTCTGGGCTGCGATGGGGTCTGGGGCTCCGCACTCTGGGCTGCGATGGGGTCTGGGGC
TCCGCGCTCTGGGCTGCGATGGGCTCTGGGGCTCTGAGCTCTGG ORF Start: ATG at 1
ORF Stop: TGA at 673 SEQ ID NO: 28 224 aa MW at 23172.1kD NOV4a,
MKTLFLGVTLGLAAALSFTLEEEDVHPEENFDAEWGQEAHVPAGAAQEGPLHLLLQRP
CG101584-01
AFWGPAPHGKACGCSLQGRAAVPTSAHLATSPAGRNSDTNREALEEFKKLVQRKGLSE Protein
EDIFTPLQTGEDGCAQSPVSLCCVCLLSPVSHDPHVLPCPPHSPCAPSLLAGAPGPCL Sequence
ASSSLEALCSGLRWGLGLRALGCDGVWGSALWAAMGSGAPRSGLRWALGL
[0337] Further analysis of the NOV4a protein yielded the following
properties shown in Table 4B. TABLE-US-00020 TABLE 4B Protein
Sequence Properties NOV4a PSort 0.7571 probability located in
outside; 0.1000 probability analysis: located in endoplasmic
reticulum (membrane); 0.1000 probability located in endoplasmic
reticulum (lumen); 0.1000 probability located in microbody
(peroxisome) SignalP Cleavage site between residues 16 and 17
analysis:
[0338] A search of the NOV4a protein against the Geneseq database,
a proprietary database that contains sequences published in patents
and patent publication, yielded several homologous proteins shown
in Table 4C. TABLE-US-00021 TABLE 4C Geneseq Results for NOV4a
NOV4a Identities/ Residues/ Similarities for Geneseq
Protein/Organism/Length [Patent Match the Matched Expect Identifier
#, Date] Residues Region Value AAB67741 Amino acid sequence of
odorant 1 . . . 126 115/141 (81%) 1e-56 binding polypeptide
OBPIIa-delta - 1 . . . 141 119/141 (83%) Homo sapiens, 147 aa.
[WO200112806-A2, 22-FEB-2001] AAB67744 Amino acid sequence of
odorant 1 . . . 71 70/85 (82%) 7e-33 binding polypeptide OBPIIb- 1
. . . 85 71/85 (83%) gamma - Homo sapiens, 85 aa. [WO200112806-A2,
22-FEB-2001] AAB67743 Amino acid sequence of odorant 31 . . . 71
38/41 (92%) 1e-17 binding polypeptide OBPIIb-beta - 139 . . . 179
38/41 (92%) Homo sapiens, 179 aa. [WO200112806-A2, 22-FEB-2001]
ABG11867 Novel human diagnostic protein 92 . . . 154 46/74 (62%)
3e-13 #11858 - Homo sapiens, 200 aa. 130 . . . 198 47/74 (63%)
[WO200175067-A2, 11-OCT-2001] ABG11867 Novel human diagnostic
protein 92 . . . 154 46/74 (62%) 3e-13 #11858 - Homo sapiens, 200
aa. 130 . . . 198 47/74 (63%) [WO200175067-A2, 11-OCT-2001]
[0339] In a BLAST search of public sequence datbases, the NOV4a
protein was found to have homology to the proteins shown in the
BLASTP data in Table 4D. TABLE-US-00022 TABLE 4D Public BLASTP
Results for NOV4a NOV4a Identities/ Protein Residues/ Similarities
for Accession Match the Matched Expect Number
Protein/Organism/Length Residues Portion Value Q9NY54 PUTATIVE
ODORANT 1 . . . 126 115/141 (81%) 3e-56 BINDING PROTEIN AD - Homo 1
. . . 141 119/141 (83%) sapiens (Human), 147 aa. Q9NY51 PUTATIVE
ODORANT 1 . . . 71 70/85 (82%) 2e-32 BINDING PROTEIN BG - Homo 1 .
. . 85 71/85 (83%) sapiens (Human), 85 aa. CAC33327 SEQUENCE 11
FROM PATENT 31 . . . 71 38/41 (92%) 3e-17 WO0112806 - Homo sapiens
139 . . . 179 38/41 (92%) (Human), 179 aa (fragment). Q9NY52
PUTATIVE ODORANT- 31 . . . 71 38/41 (92%) 3e-17 BINDING PROTEIN BB
- Homo 125 . . . 165 38/41 (92%) sapiens (Human), 165 aa. Q9NPH6
Odorant-binding protein 2b 92 . . . 126 35/35 (100%) 3e-12
precursor (OBPIIb) - Homo 130 . . . 164 35/35 (100%) sapiens
(Human), 170 aa.
[0340] PFam analysis predicts that the NOV4a protein contains the
domains shown in the Table 4E. TABLE-US-00023 TABLE 4E Domain
Analysis of NOV4a Identities/ NOV4a Match Similarities for Pfam
Domain Region the Matched Region Expect Value lipocalin 92 . . .
128 13/37 (35%) 0.00022 31/37 (84%)
Example 5
[0341] The NOV5 clone was analyzed, and the nucleotide and encoded
polypeptide sequences are shown in Table 5A. TABLE-US-00024 TABLE
5A NOV5 Sequence Analysis SEQ ID NO: 29 1178 bp NOV5a, GGGATG;
GGAAAACTATGCCTGGGGCCGACGCTCTGCCCGGCTGCTGCCGCTGAGGAAA CG101707-01
GCCGGGACGCGGAGCCCCGCCGAGAGCTTCTTTGCTCCGGACGCCCCTGGACGTGGCG DNA
GGCAGCCGCGAGGGTAACCACCATGATCCCCTGGGTGCTCCTGGCCTGTGCCCTCCCC Sequence
TGTGCTGCTGACCCACTGCTTGGCGCCTTTGCTCGCAGGGACTTCCGGAAAGGCTCCC
CTCAACTGGTCTGCAGCCTGCCTGGCCCCCAGGGCCCACCCGGCCCCCCAGGAGCCCC
AGGGCCCTCAGGAATGATGGGACGAATGGGCTTTCCTGGCAAAGACGGCCAAGATGGA
CACGACGGCGACCGGGGGGACAGCGGAGAGGAAGGTCCACCTGGCCGGACAGGTAACC
GGGGAAAGCCAGGACCAAAGGGCAAAGCCGGGGCCATTGGGCGGGCTGGCCCCCGTGG
CCCCAAGGGGGTCAACGGTACCCCCGGGAAGCATGGCACACCAGGCAAGAAGGGGCCC
AAGGGCAAGAAGGGGGAGCCAGGCCTCCCAGGCCCCTGCAGCTGTGGCAGTGGCCATA
CCAAGTCAGCTTTCTCGGTGGCAGTGACCAAGAGCTACCCACGGGAGCGGCTGCCCAT
CAAGTTTGACAAGATTCTGATGAACGAGGGTGGCCACTACAATGCTTCCAGCGGCAAG
TTCGTCTGCGGCGTGCCTGGGATCTACTACTTCACCTACGACATCACGCTGGCCAACA
AGCACCTGGCCATCGGCCTGGTGCACAACGGCCAGTACCGCATCCGGACCTTTGATGC
CAACACCGGCAACCACGATGTGGCCTCAGGCTCCACCATCCTGGCTCTCAAGCAGGGT
GACGAAGTTTGGCTGCAGATCTTCTACTCAGAGCAGAACGGGCTCTTCTATGACCCTT
ACTGGACAGACAGCCTCTTTACGGGCTTCCTAATCTATGCCGACCAGGATGACCCCAA
CGAGGTATAGACATGCCACGGCGGTCCTCCAGGCAGGGAACAAGCTTCTGGACTTGGG
CTTACAGAGCAAGACCCCACAACTGTAGGCTGGGGGTGGGGGGTCGAGTGAGCGGTTC
TAGCCTCAGGCTCACCTCCTCCGCCTCTTTTTTTTCCCCTTCATTAAATCCAAACCTT
TTTATTCATCCAAAAAAA ORF Start: ATG at 4 ORF Stop: TAG at 994 SEQ ID
NO: 30 330 aa MW at 34833.2kD NOV5a,
MGKLCLGPTLCPAAAAEESRDAEPRRELLCSGRPWTWRAAARVTTMIPWVLLACALPC
CG101707-01
AADPLLGAFARRDFRKGSPQLVCSLPGPQGPPGPFGAPGPSGMMGRMGFPGKDGQDGH Protein
DGDRGDSGEEGPPGRTGNRGKPGPKGKAGAIGRAGPRGPKGVNGTPGKHGTPGKKGPK Sequence
GKKGEPGLPGPCSCGSGHTKSAFSVAVTKSYPRERLPIKFDKILMNEGGHYNASSGKF
VCGVPGIYYFTYDITLANKHLAIGLVHNGQYRIRTFDANTGNHDVASGSTILALKQGD
EVWLQIFYSEQNGLFYDPYWTDSLFTGFLIYADQDDPNEV
[0342] Further analysis of the NOV5a protein yielded the following
properties shown in Table 5B. TABLE-US-00025 TABLE 5B Protein
Sequence Properties NOV5a PSort 0.7900 probability located in
plasma membrane; analysis: 0.4043 probability located in microbody
(peroxisome); 0.3000 probability located in Golgi body; 0.2000
probability located in endoplasmic reticulum (membrane) SignalP
Cleavage site between residues 61 and 62 analysis:
[0343] A search of the NOV5a protein against the Geneseq database,
a proprietary database that contains sequences published in patents
and patent publication, yielded several homologous proteins shown
in Table 5C. TABLE-US-00026 TABLE 5C Geneseq Results for NOV5a
NOV5a Identities/ Residues/ Similarities for Geneseq
Protein/Organism/Length Match the Matched Expect Identifier [Patent
#, Date] Residues Region Value AAU19557 Human diagnostic and
therapeutic 1 . . . 330 329/330 (99%) 0.0 polypeptide (DITHP) #143
- Homo 2 . . . 331 329/330 (99%) sapiens, 331 aa. [WO200162927- A2,
30-AUG-2001] AAB50374 Human adipocyte complement 46 . . . 330
285/285 (100%) e-177 related protein homologue zacrp2 - 1 . . . 285
285/285 (100%) Homo sapiens, 285 aa. [WO200073448-A1, 07-DEC- 2000]
AAY54321 A polypeptide designated 46 . . . 330 285/285 (100%) e-177
ACRP30R1L which is a 1 . . . 285 285/285 (100%) homologue of ACRP30
- Homo sapiens, 285 aa. [WO9959618-A1, 25-NOV-1999] AAB30232 Human
adipocyte complement 46 . . . 330 285/285 (100%) e-177 related
protein homologue zacrp2 - 1 . . . 285 285/285 (100%) Homo sapiens,
285 aa. [WO200063376-A1, 26-OCT- 2000] ABB72178 Rat protein
isolated from skin cells 42 . . . 330 271/289 (93%) e-168 SEQ ID
NO: 294 - Rattus sp, 294 6 . . . 294 278/289 (95%) aa.
[WO200190357-A1, 29-NOV- 2001]
[0344] In a BLAST search of public sequence datbases, the NOV5a
protein was found to have homology to the proteins shown in the
BLASTP data in Table 5D. TABLE-US-00027 TABLE 5D Public BLASTP
Results for NOV5a NOV5a Identities/ Protein Residues/ Similarities
for Accession Match the Matched Expect Number
Protein/Organism/Length Residues Portion Value Q9BXJ5
Complement-c1q tumor necrosis 46 . . . 330 285/285 (100%) e-177
factor-related protein 2 precursor - 1 . . . 285 285/285 (100%)
Homo sapiens (Human), 285 aa. Q9D8U4 1810033K05RIK PROTEIN- 42 . .
. 330 272/289 (94%) e-168 Mus musculus (Mouse), 294 aa. 6 . . . 294
279/289 (96%) CAC21967 SEQUENCE 14 FROM PATENT 76 . . . 325 160/250
(64%) 1e-96 WO0073448 - Mus musculus 29 . . . 278 191/250 (76%)
(Mouse), 289 aa. CAC21966 SEQUENCE 1 FROM PATENT 76 . . . 325
159/250 (63%) 3e-96 WO0073448 - Homo sapiens 43 . . . 292 192/250
(76%) (Human), 303 aa. Q9BXJ2 Complement-c1q tumor necrosis 76 . .
. 325 159/250 (63%) 3e-96 factor-related protein 7 precursor - 29 .
. . 278 192/250 (76%) Homo sapiens (Human), 289 aa.
[0345] PFam analysis predicts that the NOV5a protein contains the
domains shown in the Table 5E. TABLE-US-00028 TABLE 5E Domain
Analysis of NOV5a Identities/ Similarities for Pfam the Matched
Expect Domain NOV5a Match Region Region Value Collagen 83 . . . 141
32/60 (53%) 3.3e-05 40/60 (67%) Collagen 142 . . . 201 23/60 (38%)
0.0014 37/60 (62%) C1q 196 . . . 320 45/138 (33%) 2.3e-38 93/138
(67%)
Example 6
[0346] The NOV6 clone was analyzed, and the nucleotide and encoded
polypeptide sequences are shown in Table 6A. TABLE-US-00029 TABLE
6A NOV6 Sequence Analysis SEQ ID NO: 31 1611 bp NOV6a,
GGAGCGTCTGTTGGGTCCGGGCCGCCGGCTTCGCCCTCGCCATGGCGCCCTGGCTGCA
CG101836-01
GCTCCTGTCGCTGCTGGGGCTGCTCCCGGGCGCAGTGGCCGCCCCCGCCCAGCCCCGA DNA
GCCGCCAGCTTTCAGGCCTGGGGGCCGCCGTCCCCGCAGCTGCTGGCGCCCACCCGCT Sequence
TCGCGCTGGAGATGTTCAACCGCGGCCGGGCTGCGGGGACGCGGGCCGTGCTGGGCCT
TGTGCGCGACCGTCCGCGCCTCACCTACTCCTCTCTCCAGGCGGGCCAGGGGTCGCTG
TACTCCCTGGAGGCCACCCTGGAGGAGCCACCCTGCAACGACCCCATGGTGTGCCGGC
TCCCCGTGTCCAAGAAAACCCTGGTGACTTTCAAAGTCCTGGATGAGCTCGGGGGGCG
CGTGCTGCTGCGGAAGGACTGTGGCCCAGTGGACACCAAGGTTCCAGGTGCTGGGGAG
CCCAAGTCAGCCTTCACTCAGGGCTCAGCCATGATTTCTTCTCTGTCCCAAAACCATC
CAGACAACAGAAACGAGACTTTCAGCTCAGTCATTTCCCTGTTGAATGAGGATCCCCT
GTCCCAGGACTTGCCTGTGAAGATGGCTTCAATCTTCAAGAACTTTGTCATTACCTAT
AACCGGACATATGAGTCAAAGGAAGAAGCCCGGTGGCGCCTGTCCGTCTTTGTCAATA
ACATGGTGCGAGCACAGAAGATCCAGGCCCTGGACCGTGGCACAGCTCAGTATGGAGT
CACCAAGTTCAGTGATCTCACAGAGGAGGAGTTCCGCACTATCTACCTGAATACTCTC
CTGAGAAAAGAGCCTGGCAACAAGATGAAGCAAGCCAAGTCTGTGGGTGACCTCGCCC
CACCTGAATGGGACTGGAGGAGTAAGGGGGCTGTCACAAAAGTCAAAGACGAGGGCAT
GTGTGGCTCCTGCTGGGCCTTCTCAGTCACAGGCAATGTGGAGGGCCAGTGGTTTCTC
AACCAGGGGACCCTGCTCTCCCTCTCTGAACAGGAGCTCTTGGACTGTGACAAGATGG
ACAAGGCCTGCATGGGCGGCTTGCCCTCCAATGCCTACTCGGCCATAAAGAATTTGGG
AGGGCTGGAGACAGAGGATGACTACAGCTACCAGGGTCACATGCAGTCCTGCAACTTC
TCAGCAGAGAAGGCCAAGGTCTACATCAATGACTCCGTGGAGCTGAGCCAGAACGAGC
AGGAGCTGGCAGCCTGGCTGGCCAAGAGAGGCCCAATCTCCGTGGCCATCAATGCCTT
TGGCATGCAGTTTTACCGCCACGGGATCTCCCGCCCTCTCCGGCCCCTCTGCAGCCCT
TGCGTCATTGACCATGCGGTGTTGCTTGTGGGCTACGGAACCGTGAGTTCTGACGTTC
CCTTTTGGGCCATCAAGAACAGCTGGGGCACTGACTGGGGTGAGAAGGGTTACTACTA
CTTGCATCGCGGGTCCGGGGCATGTGGCGTGAACACCATGGCCAGCTCGGCGGTGGTG
GACTGAAGAGGGGCCCCCAGCTCGGGACCTGGTGCTGATCAGAGTGGCTGCTGCCCCA
GCCTGACATGTGTCCAGGCCCCTCCCCGGGAGGTACAGCTGGCAG ORF Start: ATG at 42
ORF Stop: TGA at 1512 SEQ ID NO: 32 490 aa MW at 53794.7kD NOV6a,
MAPWLQLLSLLGLLPGAVAAPAQPRAASFQAWGPPSPQLLAPTRFALEMFNRGRAAGT
CG101836-01
DELGGRVLLRKDCGPVDTKVPGAGEPKSAFTQGSANISSLSQNHPDNRNETFSSVISL Protein
LNEDPLSQDLPVKMASIFKNFVITYNRTYESKEEARWRLSVFVNNMVRAQKIQALDRG Sequence
TAQYGVTKFSDLTEEEFRTIYLNTLLRKEPGNKMKQAKSVGDLAPPEWDWRSKGAVTK
VKDQGMCGSCWAFSVTGNVEGQWFLNQGTLLSLSEQELLDCDKMDKACMGGLPSNAYS
AIKNLGGLETEDDYSYQGHMQSCNFSAEKAKVYINDSVELSQNEQELAAWLAKRGPIS
VAINAFGMQFYRHGISRPLRPLCSPCVIDHAVLLVGYGTVSSDVPFWAIKNSWGTDWG
EKGYYYLHRGSGACGVNTMASSAVVD SEQ ID NO: 33 1226 bp NOV6b,
GCTTCGCCCTCGCCATGGCGCCCTGGCTGCAGCTCCTGTCGCTGCTGGGGCTGCTCCC
CG101836-02
GGGCGCAGTGGCCGCCCCCGCCCAGCCCCAAGTCCTGGATGAGCTCGGAAGACACGTG DNA
CTGCTGCGGAAGGACTGTGGCCCAGTGGACACCAAGGTTCCAGGTGCTGGGGAGCCCA Sequence
AGTCAGCCTTCACTCAGGGCTCAGCCATGATTTCTTCTCTGTCCCAAAACCATCCAGA
CAACAGAAACGAGACTTTCAGCTCAGTCATTTCCCTGTTGAATGAGGATCCCCTGTCC
CAGGACTTGCCTGTGAAGATGGCTTCAATCTTCAAGAACTTTGTCATTACCTATAACC
GGACATATGAGTCAAAGGAAGAAGCCCGGTGGCGCCTGTCCGTCTTTGTCAATAACAT
GGTGCGAGCACAGAAGATCCAGGCCCTGGACCGTGGCACAGCTCAGTATGGAGTCACC
AAGTTCAGTGATCTCACAGAGGAGGAGTTCCGCACTATCTACCTGAATACTCTCCTGA
GGAAAGAGCCTGGCAACAAGATGAAGCAAGCCAAGTCTGTGGGTGACCTCGCCCCACC
TGAATGGGACTGGAGGAGTAAGGGGGCTGTCACAAAAGTCAAAGACCAGGGCATGTGT
GGCTCCTGCTGGGCCTTCTCAGTCACAGGCAATGTGGAGGGCCAGTGGTTTCTCAACC
AGGGGACCCTGCTCTCCCTCTCTGAACAGGAGCTCTTGGACTGTGACAAGATGGACAA
GGCCTGCATGGGCGGCTTGCCCTCCAATGCCTACTCGGCCATAAAGAATTTGGGAGGG
CTGGAGACAGAGGATGACTACAGCTACCAGGGTCACATGCAGTCCTGCAACTTCTCAG
CAGAGAAGGCCAAGGTCTACATCAATGACTCCGTGGAGCTGAGCCAGAACGAGCAGAA
GCTGGCAGCCTGGCTGGCCAAGAGAGGCCCAATCTCCGTGGCCATCAATGCCTTTGGC
ATGCAGTTTTACCGCCACGGGATCTCCCGCCCTCTCCGGCCCCTCTGCAGCCCTTGGC
TCATTGACCATGCGGTGTTGCTTGTGGGCTACGGCAACCGCTCTGACGTTCCCTTTTG
GGCCATCAAGAACAGCTGGGGCACTGACTGGGGTGAGAAGGGTTACTACTACTTGCAT
CGCGGGTCCGGGGCCTGTGGCGTGAACACCATGGCCAGCTCGGCGGTGGTGGACTGAA GAGGGGCC
ORF Start: ATG at 15 ORE Stop: TGA at 1215 SEQ ID NO: 34 400 aa MW
at 44237.8kD NOV6b,
MAPWLQLLSLLGLLPGAVAAPAQPQVLDELGRHVLLRKDCGPVDTKVPGAGEPKSAFT
CG101836-02
QGSAMISSLSQNHPDNRNETFSSVISLLNEDPLSQDLFVKMASIFKNFVITYNRTYES Protein
KEEARWRLSVFVNNMVRAQKIQALDRGTAQYGVTKFSDLTEEEFRTIYLNTLLRKEPG Sequence
NKMKQAKSVGDLAPPEWDWRSKGAVTKVKDQGMCGSCWAFSVTGNVEGQWFLNQGTLL
SLSEQELLDCDKMDKACMGGLPSNAYSAIKNLGGLETEDDYSYQGHMQSCNFSAEKAK
VYINDSVELSQNEQKLAAWLAKRGFISVAINAFGMQFYRHGISRPLRPLCSPWLIDHA
VLLVGYGNRSDVPFWAIKNSWGTDWGEKGYYYLHRGSGACGVNTMASSAVVD
[0347] Sequence comparison of the above protein sequences yields
the following sequence relationships shown in Table 6B.
TABLE-US-00030 TABLE 6B Comparison of NOV6a against NOV6b.
Identities/ Protein NOV6a Residues/ Similarities for Sequence Match
Residues the Matched Region NOV6b 117 . . . 490 366/374 (97%) 28 .
. . 400 368/374 (97%)
[0348] Further analysis of the NOV6a protein yielded the following
properties shown in Table 6C. TABLE-US-00031 TABLE 6C Protein
Sequence Properties NOV6a PSort 0.4514 probability located in
outside; 0.1900 probability analysis: located in lysosome (lumen);
0.1000 probability located in endoplasmic reticulum (membrane);
0.1000 probability located in endoplasmic reticulum (lumen) SignalP
Cleavage site between residues 20 and 21 analysis:
[0349] A search of the NOV6a protein against the Geneseq database,
a proprietary database that contains sequences published in patents
and patent publication, yielded several homologous proteins shown
in Table 6D. TABLE-US-00032 TABLE 6D Geneseq Results for NOV6a
Identities/ Similarities for Geneseq Protein/Organism/Length NOV6a
Residues/ the Matched Expect Identifier [Patent #, Date] Match
Residues Region Value AAB11960 Human cathepsin Y - 1 . . . 490
469/491 (95%) 0.0 Homo sapiens, 484 aa. 1 . . . 484 476/491 (96%)
[JP2000157263-A, 13-JUN-2000] AAW53200 Human spleen-derived
cysteine 99 . . . 490 381/393 (96%) 0.0 protease - Homo sapiens,
392 aa. 1 . . . 392 386/393 (97%) [JP10099084-A, 21-APR-1998]
AAW37957 Amino acid sequence of human 99 . . . 490 378/393 (96%)
0.0 cathepsin polypeptide-1 - 1 . . . 392 384/393 (97%) Homo
sapiens, 392 aa. [WO9813484-A1, 02-APR-1998] AAY45041 Human Apop2
protein - 152 . . . 490 333/339 (98%) 0.0 Homo sapiens, 338 aa. 1 .
. . 338 335/339 (98%) [WO200007545-A2, 17-FEB-2000] AAB51802 Gene
26 human secreted protein 256 . . . 490 229/235 (97%) e-135
homologous amino acid sequence 1 . . . 234 231/235 (97%) #131 -
Homo sapiens, 234 aa. [WO200061625-A1, 19-OCT-2000]
[0350] In a BLAST search of public sequence datbases, the NOV6a
protein was found to have homology to the proteins shown in the
BLASTP data in Table 6E. TABLE-US-00033 TABLE 6E Public BLASTP
Results for NOV6a NOV6a Identities/ Protein Residues/ Similarities
for Accession Match the Matched Expect Number
Protein/Organism/Length Residues Portion Value Q9UBX1 Cathepsin F
precursor 1 . . . 490 469/491 (95%) 0.0 (EC 3.4.22.41) (CATSF) - 1
. . . 484 476/491 (96%) Homo sapiens (Human), 484 aa. Q9R013
Cathepsin F precursor 1 . . . 490 350/493 (70%) 0.0 (EC 3.4.22.41)
- Mus musculus 1 . . . 462 401/493 (80%) (Mouse), 462 aa. Q9ES93
CATHEPSIN F - Mus musculus 1 . . . 490 348/493 (70%) 0.0 (Mouse),
462 aa. 1 . . . 462 399/493 (80%) T46294 hypothetical protein 166 .
. . 444 276/279 (98%) e-161 DKFZp434F0610.1 - human, 308 1 . . .
279 278/279 (98%) aa (fragment). Q99KQ9 SIMILAR TO CATHEPSIN F -
188 . . . 490 249/303 (82%) e-153 Mus musculus (Mouse), 302 aa. 1 .
. . 302 281/303 (92%)
[0351] PFam analysis predicts that the NOV6a protein contains the
domains shown in the Table 6F. TABLE-US-00034 TABLE 6F Domain
Analysis of NOV6a Identities/ Similarities for the Matched Expect
Pfam Domain NOV6a Match Region Region Value gpdh 404 . . . 413 5/10
(50%) 0.35 8/10 (80%) Peptidase_C1 276 . . . 488 102/337 (30%)
1.8e-104 184/337 (55%)
Example 7
[0352] The NOV7 clone was analyzed, and the nucleotide and encoded
polypeptide sequences are shown in Table 7A. TABLE-US-00035 TABLE
7A NOV7 Sequence Analysis SEQ ID NO: 35 1704 bp NOV7a,
TGGTAGATGTGGCATTTGCATGCTGAGGCCGCGAGTCCCGGCTGACCCCGTCGGTGCC
CG102221-01
TCTCCAGGGCTTCTCTGGGCCGCGCCTCTGCAGACTGCGCAGCCATGCTGCATCTGCT DNA
GGCGCTCTTCCTGCACTGCCTCCCTCTGGCCTCTGGGGACTATGACATCTGCAAATCC Sequence
TGGGTGACCACAGATGAGGGCCCCACCTGGGAGTTCTACGCCTGCCAGCCCAAGGTGA
TGCGCCTGAAGGACTACGTCAAGGTGAAGGTGGAGCCCTCAGGCATCACATGTGGAGA
CCCCCCTGAGAGGTTCTGCTCCCATCCCTACCTATGCAGCAACGAGTGTGACGCCTCC
AACCCGGACCTGGCCCACCCGCCCAGGCTCATGTTCGACAAGGAGGAGGAGGGCCTGG
CCACCTACTGGCAGAGCATCACCTGGAGCCGCTACCCCAGCCCGCTGGAAGCCAACAT
CACCCTTTCGTGGAACAAGACCGTGGAGCTGACCGACGACGTGGTGATGACCTTCGAG
TACGGCCGGCCCACGGTCATGGTCCTGGAGAAGTCCCTGGACAACGGGCGCACCTGGC
AGCCCTACCAGTTCTACGCCGAGGACTGCATGGAGGCCTTCGGTATGTCCGCCCGCCG
GGCCCGCGACATGTCATCCTCCAGCGCGCACCGCGTGCTCTGCACCGAGGAGTACTCG
CGCTGGGCAGGCTCCAAGAAGGAGAAGCACGTGCGCTTCGAGGTGCGGGACCGCTTCG
CCATCTTTGCCGGCCCCGACCTGCGCAACATGGACAACCTCTACACGCGGCTGGAGAG
CGCCAAGGGCCTCAAGGAGTTCTTCACCCTCACCGACCTGCGCATGCGGCTGCTGCGC
CCGGCGCTGGGCGGCACCTATGTGCAGCGGGAGAACCTCTACAAGTACTTCTACGCCA
TCTCCAACATCGAGGTCATCGGCAGGTGCAAGTGCAACCTGCACGCCAACCTGTGCTC
CATGCGCGAGGGCAGCCTGCAGTGCGAGTGCGAGCACAACACCACCGGCCCCGACTGC
GGCAAGTGCAAGAAGAATTTCCGCACCCGGTCCTGGCGGGCCGGCTCCTACCTGCCGC
TGCCCCATGGCTCTCCCAACGCCTGTGACTGCGAATGCTACGGTCACTCCAACCGCTG
CAGCTACATTGACTTCCTGAATGTGGTGACCTGCGTCAGCTGCAAGCACAACACGCGA
GGTCAGCACTGCCAGCACTGCCGGCTGGGCTACTACCGCAACGGCTCGGCAGAGCTGG
ATGATGAGAACGTCTGCATTGAGTGTAACTGCAACCAGATAGGCTCCGTGCACGACCG
GTGCAACGAGACCGGCTTCTGCGAGTGCCGCGAGGGCGCGGCGGGCCCCAAGTGCGAC
GACTGCCTCCCCACGCACTACTGGCGCCAGGGCTGCTACCCCAACGTGTGCGACGACG
ACCAGCTGCTGTGCCAGAACGGAGGCACCTGCCTGCAGAACCAGCGCTGCGCCTGCCC
GCGCGGCTACACCGGCGTGCGCTGCGAGCAGCCCCGCTGCGACCCCGCCGACGATGAC
GGCGGTCTGGACTGCGACCGCGCGCCCGGGGCCGCCCCGCGCCCCGCCACCCTGCTCG
GCTGCCTGCTGCTGCTGGGGCTGGCCGCCCGCCTGGGCCGCTGAGCCCCGCCCGGAGG
ACGCTCCCCGCACCCGGAGGCC ORF Start: ATG at 103 ORE Stop: TGA at 1666
SEQ ID NO: 36 521 aa MW at 58964.0kD NOV7a,
MLHLLALFLHCLPLASGDYDICKSWVTTDEGPTWEFYACQPKVMRLKDYVKVKVEPSG
CG102221-01
ITCGDFPERFCSHPYLCSNECDASNPDLAHPPRLMFDKEEEGLATYWQSITWSRYPSP Protein
LEANITLSWNKTVELTDDVVMTFEYGRPTVMVLEKSLDNGRTWQPYQFYAEDCMEAFG Sequence
MSARRARDMSSSSAHRVLCTEEYSRWAGSKKEKHVRFEVRDRFAIFAGPDLRNMDNLY
TRLESAKGLKEFFTLTDLRNRLLRPALGGTYVQRENLYKYFYAISNIEVIGRCKCNLH
ANLCSMREGSLQCECEHNTTGPDCGKCKKNFRTRSWRAGSYLPLPHGSPNACDCECYG
HSNRCSYIDFLNVVTCVSCKHNTRGQHCQHCRLGYYRNGSAELDDENVCIECNCNQIG
SVHDRCNETGFCECREGAAGPKCDDCLPTHYWRQGCYPNVCDDDQLLCQNGGTCLQNQ
RCACPRGYTGVRCEQPRCDPADDDGGLDCDRAPGAAPRPATLLGCLLLLGLAARLGR
[0353] Further analysis of the NOV7a protein yielded the following
properties shown in Table 7B. TABLE-US-00036 TABLE 7B Protein
Sequence Properties NOV7a PSort 0.7000 probability located in
plasma membrane; 0.3000 analysis: probability located in microbody
(peroxisome); 0.2000 probability located in endoplasmic reticulum
(membrane); 0.1000 probability located in mitochondrial inner
membrane SignalP Cleavage site between residues 18 and 19
analysis:
[0354] A search of the NOV7a protein against the Geneseq database,
a proprietary database that contains sequences published in patents
and patent publication, yielded several homologous proteins shown
in Table 7C. TABLE-US-00037 TABLE 7C Geneseq Results for NOV7a
NOV7a Identities/ Residues/ Similarities for Geneseq
Protein/Organism/Length Match the Matched Expect Identifier [Patent
#, Date] Residues Region Value ABB53284 Human polypeptide #24 - 1 .
. . 521 521/533 (97%) 0.0 Homo sapiens, 1 . . . 533 521/533 (97%)
533 aa. [WO200181363-A1, 01-NOV-2001] ABB05418 Mouse membrane bound
type 17 . . . 519 308/515 (59%) 0.0 netrin protein SEQ ID NO: 8 -
28 . . . 537 379/515 (72%) Mus musculus, 539 aa. [JP2001327289-A,
27-NOV-2001] ABB53283 Human polypeptide #23 - 1 . . . 284 284/286
(99%) e-170 Homo sapiens, 286 aa. 1 . . . 286 284/286 (99%)
[WO200181363-A1, 01-NOV-2001] ABB05419 Mouse membrane bound type 17
. . . 427 220/438 (50%) e-124 netrin protein SEQ ID NO: 10 - 28 . .
. 461 277/438 (63%) Mus musculus, 483 aa. [JP2001327289-A,
27-NOV-2001] AAB65181 Human PRO1133 (UNQ571) protein 13 . . . 427
210/419 (50%) e-123 sequence SEQ ID NO: 129 - 24 . . . 416 274/419
(65%) Homo sapiens, 438 aa. [WO200073454-A1, 07-DEC-2000]
[0355] In a BLAST search of public sequence datbases, the NOV7a
protein was found to have homology to the proteins shown in the
BLASTP data in Table 7D. TABLE-US-00038 TABLE 7D Public BLASTP
Results for NOV7a NOV7a Identities/ Protein Residues/ Similarities
for Accession Match the Matched Expect Number
Protein/Organism/Length Residues Portion Value BAB47486 KIAA1857
PROTEIN - 1 . . . 521 520/530 (98%) 0.0 Homo sapiens 20 . . . 549
521/530 (98%) (Human), 549 aa (fragment). Q96CW9 HYPOTHETICAL 59.8
KDA 1 . . . 521 520/530 (98%) 0.0 PROTEIN - Homo sapiens 1 . . .
530 521/530 (98%) (Human), 530 aa. Q8VIP8 NETRIN-G2A - Mus musculus
1 . . . 519 493/529 (93%) 0.0 (Mouse), 530 aa. 1 . . . 528 505/529
(95%) AAL84788 LAMINET-2A - Mus musculus 1 . . . 519 492/529 (93%)
0.0 domesticus (western European 1 . . . 528 504/529 (95%) house
mouse), 530 aa. Q96JH0 KIAA1857 PROTEIN - 1 . . . 342 342/344 (99%)
0.0 Homo sapiens (Human), 438 aa 20 . . . 363 342/344 (99%)
(fragment).
[0356] PFam analysis predicts that the NOV7a protein contains the
domains shown in the Table 7E. TABLE-US-00039 TABLE 7E Domain
Analysis of NOV7a NOV7a Identities/ Match Similarities Pfam Domain
Region for the Matched Region Expect Value laminin_Nterm 39 . . .
283 79/282 (28%) 5.9e-12 134/282 (48%) laminin_EGF 285 . . . 342
15/68 (22%) 1.5e-06 38/68 (56%) laminin_EGF 344 . . . 397 18/63
(29%) 0.00013 39/63 (62%) laminin_EGF 400 . . . 442 20/59 (34%)
8.3e-09 35/59 (59%) EGF 447 . . . 477 16/47 (34%) 0.00014 22/47
(47%)
Example 8
[0357] The NOV8 clone was analyzed, and the nucleotide and encoded
polypeptide sequences are shown in Table 8A. TABLE-US-00040 TABLE
8A NOV8 Sequence Analysis SEQ ID NO: 37 910 bp NOV8a,
GGTCCGGGGGGGCTGCCGGTCCCGGGTACCATGTGTGACGGCGCCCTGCTGCCTCCGC
CG102325-01
TCGTCCTGCCCGTGCTGCTGCTGCTGGTTTGGGGACTGGACCCGGGCACAGCTGTCGG DNA
CGACGCGGCGGCCGACGTGGAGGTGGTGCTCCCGTGGCGGGTGCGCCCCGACGACGTG Sequence
CACCTGCCGCCGCTGCCCGCAGCCCCCGGGCCCCGACGGCGGCGACGCCCCCGCACGC
CCCCAGCCGCCCCGCGCGCCCGGCCCGGAGAGCGCGCCCTGCTGCTGCACCTGCCGGC
CTTCGGGCGCGAGCTGTACCTTCAGCTGCGCCGCGACCTGCGCTTCCTGTCCCGAGGC
TTCGAGGTGGAGGAGGCGGGCGCGGCCCGGCGCCGCGGGCGCCCCGCCGAGCTGTGCT
TCTACTCGGGCCGTGTGCTCGGCCACCCCGGCTCCCTCGTCTCGCTCAGCGCCTGCGG
CGCCGCCGGCGGCCTGGTACTGCCCGCGCCACCTCCGGGTCGGCCCGTCCGGTCTGTT
GCGACGCAGAGTGGTCGCCGTGGAGGGTGGGGGTGGGGCGCCTCTGCTGGAAGTCCAG
CCTCCAGGGGAACCGGAGGGAACCCCCTGCCTTTCCACCTCTCCCCATCCCCCACCCC
GGCCTTCGGTACCCTCTATAGGCAAAGGGGGTGGGAGGGGCAGCATCCCAGTCCAGCG
CCTCTGCAGCCCGTGGAACCCGCGCGGAGCTGGGGTTGCGTGGGGGTATACGCCGCCC
GCTCTAGGGAGCGCAGATCTGGCAGGGATGAAACTGTCAGGGCCCTGGACAGAGGCGC
CTTGGCCCCAATGTAGAGAACACTGCATCTGCACCGCCGTGTCAAAGTGTATGTCACG
GGAGTACCTGTGTACGTGTAGGTGTTATGTTCTTGGACTT ORF Start: ATG at 31 ORF
Stop: TAG at 826 SEQ ID NO: 38 265aa MW at 28223.0kD NOV8a,
MCDGALLPPLVLPVLLLLVWGLDPGTAVGDAAADVEVVLPWRVRPDDVHLPPLPAAPG
CG102325-01
PRRRRRPRTPPAAPRARPGERALLLHLPAFGRDLYLQLRRDLRFLSRGFEVEEAGAAR Protein
RRGRPAELCFYSGRVLGHPGSLVSLSACGAAGGLVLPAPPPGRFVRSVATQSGRRGGW Sequence
GWGASAGSPASRGTGGNPLPFHLSPSPTFAFGTLYRQRGWEGQHFSPAPLQPVEPARS
WGCVGVYAARSRERRSGRDETVRALDRGALAPM
[0358] Further analysis of the NOV8a protein yielded the following
properties shown in Table 8B. TABLE-US-00041 TABLE 8B Protein
Sequence Properties NOV8a PSort 0.8200 probability located in
outside; 0.1000 probability analysis: located in endoplasmic
reticulum (membrane); 0.1000 probability located in endoplasmic
reticulum (lumen); 0.1000 probability located in lysosome (lumen)
SignalP Cleavage site between residues 28 and 29 analysis:
[0359] A search of the NOV8a protein against the Geneseq database,
a proprietary database that contains sequences published in patents
and patent publication, yielded several homologous proteins shown
in Table 8C. TABLE-US-00042 TABLE 8C Geneseq Results for NOV8a
NOV8a Identities/ Residues/ Similarities for Geneseq
Protein/Organism/Length Match the Matched Expect Identifier [Patent
#, Date] Residues Region Value AAE10350 Human ADAMTS-J1.4 variant 1
. . . 151 151/151 (100%) 6e-85 protein - Homo sapiens, 891 aa. 1 .
. . 151 151/151 (100%) [EP1134286-A2, 19-SEP-2001] AAE10348 Human
ADAMTS-J1.2 variant 1 . . . 151 151/151 (100%) 6e-85 protein - Homo
sapiens, 635 aa. 1 . . . 151 151/151 (100%) [EP1134286-A2,
19-SEP-2001] AAE10347 Human ADAMTS-J1.1 variant 1 . . . 151 151/151
(100%) 6e-85 protein - Homo sapiens, 745 aa. 1 . . . 151 151/151
(100%) [EP1134286-A2, 19-SEP-2001] AAU72894 Human metalloprotease
partial 27 . . . 151 125/125 (100%) 1e-68 protein sequence #6 -
Homo 434 . . . 558 125/125 (100%) sapiens, 1428 aa. [WO200183782-
A2, 08-NOV-2001] AAU72900 Human metalloprotease partial 51 . . .
151 52/112 (46%) 3e-15 protein sequence #12 - Homo 142 . . . 244
59/112 (52%) sapiens, 1094 aa. [WO200183782- A2, 08-NOV-2001]
[0360] In a BLAST search of public sequence datbases, the NOV8a
protein was found to have homology to the proteins shown in the
BLASTP data in Table 8D. TABLE-US-00043 TABLE 8D Public BLASTP
Results for NOV8a NOV8a Identities/ Protein Residues/ Similarities
for Accession Match the Matched Expect Number
Protein/Organism/Length Residues Portion Value CAC86016
METALLOPROTEASE 1 . . . 151 151/151 (100%) 1e-84 DISINTEGRIN 17,
WITH 1 . . . 151 151/151 (100%) THROMBOSPONDIN DOMAINS - Homo
sapiens (Human), 1095 aa. CAC84565 ADAMTS-19 - Homo sapiens 51 . .
. 151 51/112 (45%) 1e-14 (Human), 1207 aa. 142 . . . 244 59/112
(52%) CAC86014 METALLOPROTEASE 25 . . . 259 72/248 (29%) 5e-08
DISINTEGRIN 15 WITH 13 . . . 218 100/248 (40%) THROMBOSPONDIN
DOMAINS - Homo sapiens (Human), 950 aa. Q9WUQ1 ADAMTS-1 precursor
(EC 3.4.24.--) 69 . . . 149 35/90 (38%) 1e-06 (A disintegrin and
metalloproteinase 66 . . . 153 46/90 (50%) with thrombospondin
motifs 1) (ADAM-TS 1) (ADAM-TS1) - Rattus norvegicus (Rat), 967 aa.
Q9UP79 ADAMTS-8 precursor (EC 3.4.24.--) 52 . . . 187 52/167 (31%)
3e-06 (A disintegrin and metalloproteinase 3 . . . 165 65/167 (38%)
with thrombospondin motifs 8) (ADAM-TS 8) (ADAM-TS8) (METH-2)
(METH-8) - Homo sapiens (Human), 890 aa.
[0361] PFam analysis predicts that the NOV8a protein contains the
domains shown in the Table 8E. TABLE-US-00044 TABLE 8E Domain
Analysis of NOV8a NOV8a Identities/ Match Similarities Expect Pfam
Domain Region for the Matched Region Value Pep_M12B_propep 95 . . .
192 26/119 (22%) 0.021 60/119 (50%)
Example 9
[0362] The NOV9 clone was analyzed, and the nucleotide and encoded
polypeptide sequences are shown in Table 9A. TABLE-US-00045 TABLE
9A NOV9 Sequence Analysis SEQ ID NO: 39 958 bp NOV9a,
GCAGCACCCGCAGCCAGAGCCGCGCTCGGCATGATGCCCGGGGCGCCGCTCCTGCGGC
CG102832-01
TGCTGACCGCGGTCTCTGCGGCAGTGGCAGTGGCAGTGGCCGGGGCGCCCGGGACGGT DNA
AATGCCCCCCACCACGGGGGACGCCACCCTGGCCTTCGTCTTCGACGTCACCGGCTCC Sequence
ATGTGGGACGAACTGATGCAGGTGATCGATGGCGCCTCGCGCATTCTGGAACGCAGTC
TGAGCGGCCGCAGCCAGGCCATCGCCAACTACGCGCTGGTGCCCTTCCACGACCCAGA
TATTGGCCCAGTGACCCTCACGGCGGACCCCACAGTGTTTCAGAGGGAGCTGAGAGAA
CTCTACGTGCAGGGAGGTGGTGACTGCCCGGAGATGAGTGTGGGGGCCATTAAGGCTG
CCGTGGAGGTTGCCAACCCCGGATCCTTCATCTACGTCTTTTCGGATGCCCGCGCCAA
AGACTATCACAAGAAGGAAGAGCTGCTGCGGCTCCTGCAGCTCAAGCAATCACAGGTG
GTCTTTGTGCTGACGGGGGACTGTGGCGACCGCACCCATCCTGGCTACCTGGCTTATG
AGGAGATCGCTGCCACCAGCTCTGGGCAGGTGTTCCACCTGGACAAGCAGCAAGTGAC
AGAGGTGCTGAAGTGGGTGGAGTCAGCGATCCAGGCCTCCAAGGTGCACCTGCTGTCC
ACAGACCACGAGGAGGAGGGGGAGCACACATGGAGACTCCCCTTTGACCCCAGCCTGA
AGGAGGTCACCATCTCATTGAGTGGGCCAGGGCCTGAGATTGAAGTCCAAGATCCGCT
GGGTATGGACCACCCCGGGGCTGGCCTCCTCTTTGGCCCCAAGACTGAGGTGGAAGCC
CAGGATGGGACAAAGAAAGAGACCAAGGGTGACAGGGCTTCAGACATGAGGCTCCAGG
AATAGGGAAATATGGGGTGGGGGGGACACG ORF Start: ATG at 31 ORF Stop: TAG
at 931 SEQ ID NO: 40 300 aa MW at 32481.5kD NOV9a,
MMPGAPLLRLLTAVSAAVAVAVAGAPGTVMPPTTGDATLAFVFDVTGSMWDELMQVID
CG102832-01
GASRILERSLSRRSQAIANYALVPFHDPDIGPVTLTADPTVFQRELRELYVQGGGDCP Protein
EMSVGAIKAAVEVANPGSFIYVFSDARAKDYHKKEELLRLLQLKQSQVVFVLTGDCGD Sequence
RTHPGYLAYEEIAATSSGQVFHLDKQQVTEVLKWVESAIQASKVHLLSTDHEEEGEHT
WRLPFDPSLKEVTISLSGPGPEIEVQDPLGMDHFGAGLLFGPKTEVEAQDGTKKETKG
DRASDMRLQE SEQ ID NO: 41 2916 bp NOV9b,
GCAGCACCCGCAGCCAGAGCCGCGCTCGGCATGATGCCCGGGGCGCCGCTCCTGCGGC
CG102832-02
TGCTGACCGCGGTCTCTGCGGCAGTGGCAGTGGCAGTGGCCGGGGCGCCCGGGACGGT DNA
AATGCCCCCCACCACGGGGGACGCCACCCTGGCCTTCGTCTTCGACGTCACCGGCTCC Sequence
ATGTGGGACGAACTGATGCAGGTGATCGATGGCGCCTCGCGCATTCTGGAACGCAGTC
TGAGCCGCCGCAGCCAGGCCATCGCCAACTACGCGCTGGTGCCCTTCCACGACCCAGA
TATTGGCCCAGTGACCCTCACGGCGGACCCCACAGTGTTTCAGAGGGAGCTGAGAGAA
CTCTACGTGCAGGGAGGTGGTGACTGCCCGGAGATGAGTGTGGGGGCCATTAAGGCTG
CCGTGGAGGTTGCCAACCCCGGATCCTTCATCTACGTCTTTTCGGATGCCCGCGCCAA
AGACTATCACAAGAAGGAAGAGCTGCTGCGGCTCCTGCAGCTCAAGCAATCACAGGTG
GTCTTTGTGCTGACGGGGGACTGTGGCGACCGCACCCATCCTGGCTACCTGGCTTATG
AGGAGATCGCTGCCACCAGCTCTGGGCAGGTGTTCCACCTGGACAAGCAGCAAGTGAC
AGAGGCAGGTGCTTCCGTGTTTCCAGGCAAAATTGTGCAGGAGCACAGGATCCTTTCA
GGGGCCAGCTGGGAAATGATGAACAACGCTCTCTCTGGAAAGGACAAGCACACCCATT
TCCGTGGTATAAATGCTCCCACCTCGGCTGATTCCAAGTCAGAGTTGGGAAGTGACGC
TGACACTCAGCTTTCCGGAGCCTACACAAGTGGCTCCCACACACCACTGGATCCCGCA
CAGGCACCTCTCACCGCCAGTTGGGTTAACGAGAGCCCCTACCTGGTGCTGAAGTGGG
TGGAGTCAGCGATCCAGGCCTCCAAGGTGCACCTGCTGTCCACAGACCACGAGGAGGA
GGGGGAGCACACATGGAGACTCCCCTTTGACCCCAGCCTGAAGGAGGTCACCATCTCA
TTGAGTGGGCCAGGGCCTGAGATTGAAGTCCAAGATCCGCTGGGTATGGACCACCCCG
GGGCTGGCCTCCTCTTTGGCCCCAAGACTGAGGTGGAAGCCCAGGATGGGACAAAGAA
AGAGACCAAGGGGAGGATCCTGCAGGAGGACGAGGGCCTCAACGTGCTTCTCAACATC
CCTGACTCGGCCAAGGTCGTAGCCTTTAAGCCTGAGCATCCGGGGCTGTGGTCCATCA
AGGTCTATAGCAGTGGCCGCCATTCAGTGAGGATCACAGGCGTCAGCAACATTGACTT
CCGAGCCGGCTTCTCCACTCAGCCCTTGCTGGACCTCAACCACACCCTCGAGTGGCCC
TTGCAAGGAGTCCCCATCTCCCTGGTGATCAATTCCACGGGCCTGAAGGCACCCGGCC
GCCTAGACTCGGTGGAGCTGGCACAAAGCTCAGGGAAGCCCCTCCTGACTCTGCCCAC
GAAGCCCCTCTCCAATGGCTCCACCCATCAGCTGTGGGGCGGGCCGCCCTTCCACACC
CCCAAGGAGCGCTTCTACCTCAAGGTGAAGGGCAAGGACCATGAGGGAAACCCCCTCC
TTCGTGTCTCTGGAGTGTCCTACAGTGGGGTGGCCCCAGGCGCTCCCCTCGTCAGCAT
GGCCCCCAGGATCCATGGCTACCTGCACCAGCCCCTGCTGGTCTCCTGCTCGGTGCAC
AGTGCCCTTCCCTTCCGGCTGCAGCTGCGGCGAGGTGAAGCCAGGCTGGGCGAAGAGA
GGCACTTTCAGGAGTCGGGAAACAGCAGCTGGGAGATCCTGCGGGCCTCCAAGGCCGA
GGAGGGCACGTACGAGTGCACAGCCGTCAGCAGGGCTGGGACCGGGCGAGCAAAGGCC
CAGATTGTTGTCACCCTGCACCTCAGGGTGGGGTTCGGGGCAGCACCAGGGCTTGCAC
GAAGACCCCCTCCCTTGCCTCAGCTCCTTGGTTCCTCCTGTGCTCATGTCCCTGCAGA
CCCCCCGCCGCAGCTGGTCCCTGCTCCCAACGTGACCGTGTCCCCAGGGGAGACTGCC
GTCCTATCCTGCCGGGTCCTAGGCGAGGCCCCCTACAACCTGACGTGGGTCCGGGACT
GGCGAGTCCTGCCGGCCTCGACGGGCCGAGTTGCCCAGCTGGCTGACCTGTCCCTGGA
GATCAGTGGCATCATCCCCACAGACGGCGGGAGGTACCAGTGTGTGGCCAGCAATGCC
AATGGGGTCACAAGGGCATCCGTCTGGCTCCTGGTGCGAGAGGCCCCACAGGTCAGCA
TCCACACCAGCTCCCAGCACTTCTCCCAAGGTGTGGAGGTGAAGGTCAGCTGCTCAGC
CTCTGGATACCCCACACCCCACATCTCCTGGAGCCGTGAGAGCCAAGCCCTACAAGAG
GACAGCAGAATCCATGTGGACGCACAGGGAACCCTGATTATTCAGGGGGTAGCCCCAG
AGGATGCTGGGAATTACAGCTGCCAGGCGACTAATGAGGTTGGCACTGACCAGGAGAC
GGTCACCCTCTACTACACAGACCCACCGTCGGTCTCTGCTGTAAATGCCGTGGTGCTG
GTGGCCGTTGGGGAGGAGGCTGTGTTGGTGTGTGAGGCATCTGGGGTTCCCCCGCCCC
GAGTCATCTGGTATCGAGGGGGTCTTGAAATGATCCTGGCCCCTGAGGGCTCCAGCTC
TGGGAAGCTGCGGATCCCGGCGGCTCAGGAGAGGGATGCTGGCACCTACACCTGCCGG
GCTGTCAATGAGTTGGGTGACGCCTCTGCAGAAATCCAGCTGGCGGTTGGACATGCGC
CCCAGCTGACGGAGCTGCCCCGGGATGTCACTGTGGAACTGGGGAGGAGTGCCCAGCT
GCGGCGTGGGACTTAA ORF Start: ATG at 31 ORF Stop: TAA at 2914 SEQ ID
NO: 42 961 aa MW at 102789.2kD NOV9b,
MMPGAPLLRLLTAVSAAVAVAVAGAPGTVMPPTTGDATLAFVFDVTGSMWDELMQVID
CG102832-02
GASRILERSLSRRSQAIANYALVPFHDPDIGPVTLTADPTVFQRELRELYVQGGGDCP Protein
EMSVGAIKAAVEVANPGSFIYVFSDARAKDYHKKEELLRLLQLKQSQVVFVLTGDCGD Sequence
RTHPGYLAYEEIAATSSGQVFHLDKQQVTEAGASVFPGKIVQEHRILSGASWEMMNNA
LSGKDKHTHFRGINAFTSADSKSELGSDADTQLSGAYTSGSHTPLDPAQAPLTASWVN
ESPYLVLKWVESAIQASKVHLLSTDHEEEGEHTWRLPFDPSLKEVTISLSGPGPEIEV
QDPLGMDHPGAGLLFGPKTEVEAQDGTKKETKGRILQEDEGLNVLLNIPDSAKVVAFK
PEHPGLWSIKVYSSGRHSVRITGVSNIDFRAGFSTQPLLDLNHTLEWPLQGVPISLVI
NSTGLKAPGRLDSVELAQSSGKPLLTLPTKPLSNGSTHQLWGGPPFHTPKERFYLKVK
GKDBEGNPLLRVSGVSYSGVAPGAPLVSMAPRIHGYLHQPLLVSCSVHSALPFRLQLR
RGEARLGEERHFQESGNSSWEILRASKAEEGTYECTAVSRAGTGRAKAQIVVTLHLRV
GFGAAPGLARRPPPLPQLLGSSCAHVPADPPPQLVPAPNVTVSPGETAVLSCRVLGEA
PYNLTWVRDWRVLFASTGRVAQLADLSLEISGIIPTDGGRYQCVASNANGVTRASVWL
LVREAPQVSIHTSSQHFSQGVEVKVSCSASGYPTPHISWSRESQALQEDSRIHVDAQG
TLIIQGVAPEDAGNYSCQATNEVGTDQETVTLYYTDPPSVSAVNAVVLVAVGEEAVLV
CEASGVPPPRVIWYRGGLEMILAPEGSSSGKLRIPAAQERDAGTYTCRAVNELGDASA
EIQLAVGHAPQLTELPRDVTVELGRSAQLRRGT SEQ ID NO: 43 1023 bp NOV9c,
CTCGAGTGTGGAACTCACTCTTAACGTACCTGAGGAGTGTCCAACGTCTTTGGACAAG
197195425
GCCATACTCTCATGTTCCTTTTCACTCAGCTTTACCCACACAGAAATTTTGGGGACCC DNA
ATGGGGGACTCAGCAGTTGCCAAGGTCTGCAGCCTCCTCCAAGGGGTTCCCATCTAGT Sequence
TCTCAAGAGGAAGGAGGGGGTTCTCAGTCGCCAGGTGGGCATGGCACTCCCGAGGCCA
GGTGAGCAGGTCAGTGCCTTGGGGCTCAGGGCTGCTCCGGTTCTTACCGAATTGATCC
AGTCGTTGTAGTTGGAGACCCGCGTGAAGATGGAGGGCTTGTAGTAGTAGTTGCAACC
AAGGACCGACGTGAGGCTGCCGATGCCATGCACCTCCCACCGGCCGTCAGATGCCTGA
CAGTTCAGCGGCCCACCGGAGTCTCCGTTGCAGGTGCATATCACGCCATCACCCCCAG
CACAGATCATATTCGTCTTCACGGTGCTGCCCCACCAGCCAGAGTTGGAGCAGGTGGC
ATAGTCCACAACCAGCAACCGGCCCTGCTTCAGGTCATCAGGGAGAGCCCCGTTGGTC
TGCAGCCTTCCCCAGCCCGTGACGTAGCAGGGGTAGTTGTTGGGTAGAATGGTGCCGG
CAGGAGGGAGGCAGGCCAGCTGGATCTTGTCGGTGAGGGAGACGGGGTTAGCCAGTTT
GAGCAGGGCAATGTCGTTCCCTTTGGAGACCTGGTCGGAGTTCCAGTCCTTGTGCACC
ACAATCTTAGAGACACTGACGGCCAGCGAGCCGGACTCTGCAACGTAGAGGTTATGCT
GGCCCAGCATCACGCGGTAGATCCCGGAGGAGCTGATGCAGTGGGCAGCCGTCAGGAC
CCAGCTGTTGGCTATCAGGGACCCTCCGCAGGTGTGGTACCACTGGCCATTGGAGCTG
TACTGCAGGGAGACCTGCCAGGGCCGGCTGTTGGGCCTCGCTTCTTCACCTCCAAGCA
TCCTAGACATATCAGGCGCGTAAGTGGAGACGGATCC ORF Start: at 628 ORF Stop:
end of sequence SEQ ID NO: 44 132 aa MW at 13513.0kD NOV9c,
NGAGRREAGQLDLVGEGDGVSQFEQGNVVPFGDLVGVPVLVHHNLRDTDGQRAGLCNV
197195425
EVMLAQHHAVDPGGADAVGSRQDPAVGYQGPSAGVVPLAIGAVLQGDLPGPAVGPRFF Protein
TSKHPRHIRRVSGDGS Sequence SEQ ID NO: 45 2058 bp NOV9d,
AAGCTTGTGGCAGTGGCCGGGGCGCCCGGGACGGTAATGCCCCCCACCACGGGGGACG
197192431
CCACCCTGGCCTTCGTCTTCGACGTCACCGGCTCCATGTGGGACGAACTGATGCAGGT DNA
GATCGATGGCGCCTCGCGCATTCTGGAACGCAGTCTGAGCCGCCGCAGCCAGGCCATC Sequence
GCCAACTACGCGCTGGTGCCCTTCCACGACCCAGATATTGGCCCAGTGACCCTCACGG
CGGACCCCACAGTGTTTCAGAGGGAGCTGAGAGAACTCTACGTGCAGGGAGGTGGTGA
CTGCCCGGAGATGAGTGTGGGGGCCATTAAGGCTGCCGTGGAGGTTGCCAACCCCGGA
TCCTTCATCTACGTCTTTTCGGATGCCCGCGCCAAAGACTATCACAAGAAGGAAGAGC
TGCTGCGGCTCCTGCAGGTCAAGCAATCACAGGTGGTCTTTGTGCTGACGGGGGACTG
TGGCGACCACACCCATCCTGGCTACCTGGCTTATGAGGAGATCGCTGCCACCAGCTCT
GGGCAGGTGTTCCACCTGGACAAGCAGCAAGTGACAGAGGTGCTGAAGTGGGTGGAGT
CAGCGATCCAGGCCTCCAAGGTGCACCTGCTGTCCACAGACCACGAGGAGGAGGGGGA
GCACACATGGAGACTCCCCTTTGACCCCAGCCTGAAGGAGGTCACCATCTCATTGAGT
GGGCCAGGGCCTGAGATTGAAGTCCAAGATCCGCTGGGGAGGATCCTGCAGGAGGACG
AGGGCCTCAACGTGCTTCTCAACATCCCTGACTCGGCCAAGGTCGTAGCCTTTAAGCC
TGAGCATCCGGGGCTGTGGTCCATCAAGGTCTATAGCAGTGGCCGCCATTCAGTGAGG
ATCACAGGCGTCAGCAACATTGACTTCCGAGCCGGCTTCTCCACTCAGCCCTTGCTGG
ACCTCAACCACACCCTCGAGTGGGCCTTGCAAGGAGTCCCCATCTCCCTGGTGATCAA
TTCCACGGGCCTGAAGGCACCCGGCCGCCTAGACTCGGTGGAGCTGGCACAAAGCTCA
GGGAAGCCCCTCCTGACTCTGCCCACGAAGCCCCTCTCCAATGGCTCCACCCATCAGC
TGTGGGGCGGGCCACCCTTCCACACCCCCAAGGAGCGCTTCTACCTCAAGGTGAAGGG
CAAGGACCATGAGGGAAACCCCCTCCTTCGTGTCTCTGGAGTGTCCTACAGTGGGGTG
GCCCCAGGCGCTCCCCTCGTCAGCATGGTCCCCAGGATCCATGGCTACCTGCACCAGC
CCCTGCTGGTCTCCTGCTCGGTGCACAGTGCCCTTCCCTTCCGGCTGCAGCTGCGGCG
AGGTGAAGCCAGGCTGGGCGAAGAGAGGCACTTTCAGGAGTCGGGAAACAGTAGCTGG
GAGATCCTGCGGGCCTCCAAGGCCGAGGAGGGCACGTACGAGTGCACAGCCGTCAGCA
GGGCTGGGACCGGGCGAGCAAAGGCCCAGATTGTTGTCACAGACCCCCCGCCGCAGCT
GGTCCCTGCTCCCAACGTGACCGTGTCCCCAGGGGAGACTGCCGTCCTATCCTGCCGG
GTCCTAGGCGAGGCCCCCTACAACCTGACGTGGGTCCGGGACTGGCGAGTCCTGCCGG
CCTCGACGGGCCGAGTTGCCCAGCTGGCTGACCTGTCCCTGGAGATCAGTGGCATCAT
CCCCACAGACGGCGGGAGGTACCAGTGTGTGGCCAGCAATGCCAATGGGGTCACAAGG
GCATCCGTCTGGCTCCTGGTGCGAGAGGTCCCACAGGTCAGCATCCACACCAGCTCCC
AGCACTTCTCCCAAGGTGTGGAGGTGAAGGTCAGCTGCTCAGCCTCTGGATACCCCAC
ACCCCACATCTCCTGGAGCCGTGAGAGCCAAGCCCTACAAGAGGACAGCAGAATCCAT
GTGGAGGCACAGGGAACCCTGATTATTCAGGGGGTAGCCCCAGAGGATGCTGGGAATT
ACAGCTGCCAGGCGACTAATGAGGTTGGCACTGACCAGGAGACGGTCACCCTCTACTA
CACAGACCCACCGTCGGTCTCTGTCGAC ORF Start: at 1 ORF Stop: end of
sequence SEQ ID NO: 46 686 aa MW at 74318.2kD NOV9d,
KLVAVAGAPGTVMPPTTGDATLAFVFDVTGSMWDELMQVIDGASRILERSLSRRSQAI
197192431
ANYALVPFHDPDIGPVTLTADPTVFQRELRELYVQGGGDCPEMSVGAIKAAVEVANPG Protein
SFIYVFSDARAKDYHKKEELLRLLQLKQSQVVFVLTGDCGDHTHPGYLAYEEIAATSS Sequence
GQVFHLDKQQVTEVLKWVESAIQASKVHLLSTDHEEEGEHTWRLPFDPSLKEVTISLS
GPGPEIEVQDPLGRILQEDEGLNVLLNIPDSAKVVAFKPEHPGLWSIKVYSSGRHSVR
ITGVSNIDFRAGFSTQFLLDLNHTLEWPLQGVPISLVINSTGLKAPGRLDSVELAQSS
GKPLLTLPTKPLSNGSTHQLWGGPPFHTPKERFYLKVKGKDHEGNPLLRVSGVSYSGV
APGAPLVSMVPRIHGYLHQPLLVSCSVHSALPFRLQLRRGEARLGEERHFQESGNSSW
EILRASKAEEGTYECTAVSRAGTGRAKAQIVVTDPFPQLVPAPNVTVSPGETAVLSCR
VLGEAPYNLTWVRDWRVLPASTGRVAQLADLSLEISGIIFTDGGRYQCVASNANGVTR
ASVWLLVREVFQVSIHTSSQHFSQGVEVKVSCSASGYPTFHISWSRESQALQEDSRIH
VDAQGTLIIQGVAPEDAGNYSCQATNEVGTDQETVTLYYTDPPSVSVD SEQ ID NO: 47 2058
bp NOV9e,
AAGCTTGTGGCAGTGGCCGGGGCGCCCGGGACGGTAATGCCCCCCACCACGGGGGACG
197192437
CCACCCTGGCCTTCGTCTTCGACGTCACCGGCTCCATGTGGGACGAACTGATGCAGGT DNA
GATCGATGGCGCCTCGCGCATTCTGGAACGCAGTCTGAGCCGCCGCAGCCAGGCCATC Sequence
GCCAACTACGCGCTGGTGCCCTTCCACGACCCAGATATTGGCCCAGTGACCCTCACGG
CGGACCCCACAGTGTTTCAGAGGGAGCTGAGAGAACTCTACGTGCAGGGAGGTGGTGA
CTGCCCGGAGATGAGTGTGGGGGCCATTAAGGCTGCCGTGGAGGTTGCCAACCCCGGA
TCCTTCATCTACGTCTTTTCGGATGCCCGCGCCAAAGACTATCACAAGAAGGAAGAGC
TGCTGCGGCTCCTGCAGCTCAAGCAATCACAGGTGGTCTTTGTGCTGACGGGGGACTG
TGGCGACCACACCCATCCTGGCTACCTGGCTTATGAGGAGATCGCTGCCACCAGCTCT
GGGCAGGTGTTCCACCTGGACAAGCAGCAAGTGACAGAGGTGCTGAAGTGGGTGGAGT
CAGCGATCCAGGCCTCCAAGGTGCACCTGCTGTCCACAGACCACGAGGAGGAGGGGGA
GCACACATGGAGACTCCCCTTTGACCCCAGCCTGAAGGAGGTCACCATCTCATTGAGT
GGGCCAGGGCCTGAGATTGAAGTCCAAGATCCGCTGGGGAGGATCCTGCAGGAGGACG
AGGGCCTCAACGTGCTTCTCAACATCCCTGACTCGGCCAAGGTCGTAGCCTTTAAGCC
TGAGCATCCGGGGCTGTGGTCCATCAAGGTCTATAGCAGTGGCCGCCATTCAGTGAGG
ATCACAGGCGTCAGCAACATTGACTTGCGAGCCGGCTTCTCCACTCAGCCCTTGCTGG
ACCTCAACCACACCCTCGAGTGGCCCTTGCAAGGAGTCCCCATCTCCCTGGTGATCAA
TTCCACGGGCCTGAAGGCACCCGGCCGCCTAGACTCGGTGGAGCTGGCACAAAGCTCA
GGGAAGCCCCTCCTGACTCTGCCCACGAAGCCCCTCTCCAATGGCTCCACCCATCAGC
TGTGGGGCGGGCCGCCCTTCCACACCCCCAAGGAGCGCTTCTACCTCAAGGTGAAGGG
CAAGGACCATGAGGGAAACCCCCTCCTTCGTGTCTCTGGAGTGTCCTACAGTGGGGTG
GCCCCAGGCGCTCCCCTCGTCAGCATGGCCCCCAGGATCCATGGCTACCTGCACCAGC
CCCTGCTGGTCTCCTGCTCGGTGCACAGTGCCCTTCCCTTCCGGCTGCAGCTGCGGCG
AGGTGAAGCCAGGCTGGGCGAAGAGAGGCACTTTCAGGAGTCGGGAAACAGCAGCTGG
GAGATCCTGCGGGCCTCCAAGGCCGAGGAGGGCACGTACGAGTGCACAGCCGTCAGCA
GGGCTGGGACCGGGCGAGCAAAGGCCCAGATTGTTGTCACAGACCCCCCGCCGCAGCT
GGTCCCTGCTCCCAACGTGACCGTGTCCCCAGGGGAGACTGCCGTCCTATCCTGCCGG
GTCCTAGGCGAGGCCCCCTACAACCTGACGTGGGTCCGGGACTGGCGAGTCCTGCCGG
CCTCGACGGGCCGAGTTGCCCAGCTGGCTGACCTGTCCCTGGAGATCAGTGGCATCAT
CCCCACAGACGGCGGGAGGTACCAGTGTGTGGCCAGCAATGCCAATGGGGTCACAAGG
GCATCCGTCTGGCTCCTGGTGCGAGAGGCCCCACAGGTCAGCATCCACACCAGCTCCC
AGCACTTCTCCCAAGGTGTGGAGGTGAAGGTCAGCTGCTCAGCCTCTGGATACCCCAC
ACCCCACATCTCCTGGAGCCGTGAGAGCCAAGCCCTACAAGAGGACAGCAGAATCCAT
GTGGACGCACAGGGAACCCTGATTATTCAGGGGGTAGCCCCAGAGGATGCTGGGAATT
ACAGCTGCCAGGCGACTAATGAGGTTGGCACTGACCAGGAGACGGTCACCCTCTACGA
CACAGACCCACCGTCGGTCTCTGTCGAC ORF Start: at 1 ORF Stop: end of
sequence SEQ ID NO: 48 686 aa MW at 74214.0kD NOV9e,
KLVAVAGAPGTVMPPTTGDATLAFVFDVTGSMWDELMQVIDGASRILERSLSRRSQAI
197192437
ANYALVPFHDPDIGPVTLTADPTVFQRELRELYVQGGGDCPEMSVGAIKAAVEVANPG Protein
SFIYVFSDARAKDYHKKEELLRLLQLKQSQVVFVLTGDCGDHTHFGYLAYEEIAATSS Sequence
GQVFHLDKQQVTEVLKWVESAIQASKVHLLSTDHEEEGEHTWRLFFDPSLKEVTISLS
GPGPEIEVQDPLGRILQEDEGLNVLLNIPDSAKVVAFKPEHPGLWSIKVYSSGRHSVR
ITGVSNIDFRAGFSTQPLLDLNHTLEWPLQGVPISLVINSTGLKAPGRLDSVELAQSS
GKPLLTLPTKPLSNGSTHQLWGGPPFHTPKERFYLKVKGKDHEGNPLLRVSGVSYSGV
APGAPLVSMAPRIHGYLHQPLLVSCSVHSALPFRLQLRRGEARLGEERHFQESGNSSW
EILRASKAEEGTYECTAVSRAGTGRAKAQIVVTDPPPQLVPAPNVTVSPGETAVLSCR
VLGEAPYNLTWVRDWRVLPASTGRVAQLADLSLEISGIIPTDGGRYQCVASNANGVTR
ASVWLLVREAPQVSIHTSSQHFSQGVEVKVSCSASGYPTPHISWSRESQALQEDSRIH
VDAQGTLIIQGVAPEDAGNYSCQATNEVGTDQETVTLYIJTDPPSVSVD SEQ ID NO: 49
2058 bp NOV9f,
AAGCTTGTGGCAGTGGCCGGGGCGCCGGGGACGGTAATGCCCCCCACCACGGGGGACG
197192443
CCACCCTGGCCTTCGTCTTCGACGTCACCGGCTCCATGTGGGACGAACTGATGCAGGT DNA
GATCGATGGCGCCTCGCGCATTCTGGAACGCAGTCTGAGCCGCCGCAGCCAGGCCATC Sequence
GCCAACTACGCGCTGGTGCCCTTCCACGACCCAGATATTGGCCCAGTGACCCTCACGG
CGGACCCCACAGTGTTTCAGAGGGAGCTGAGAGAACTCTACGTGCAGGGAGGTGGTGA
CTGCCCGGAGATGAGTGTGGGGGCCATTAAGGCTGCCGTGGAGGTTGCCAACCCCGGA
TCCTTCATCTACGTCTTTTCGGATGCCCGCGCCAAAGACTATCACAAGAAGGAAGAGC
TGCTGCGGCTCCTGCAGCTCAAGCAATCACAGGTGGTCTTTGTGCTGACGGGGGACTG
TGGCGACCACACCCATCCTGGCTACCTGGCTTATGAGGAGATCGCTGCCACCAGCTCT
GGGCAGGTGTTCCACCTGGACAAGCAGCAAGTGACAGAGGTGCTGAAGTGGGTGGAGT
CAGCGATCCAGGCCTCCAAGGTGCACCTGCTGTCCACAGACCACGAGGAGGAGGGGGA
GCACACATGGAGACTCCCCTTTGACCCCAGCCTGAAGGAGGTCACCATCTCATTGAGT
GGGCCAGGGCCTGAGATTGAAGTCCAAGATCCGCTGGGGAGGATCCTGCAGGAGGACG
AGGGCCTCAACGTGCTTCTCAACATCCCTGACTCGGCCAAGGTCGTAGCCTTTAAGCC
TGAGCATCCGGGGCTGTGGTCCATCAAGGTCTATAGCAGTGGCCGCCATTCAGTGAGG
ATCACAGGCGTCAGCAACATTGACTTCCGAGCCGGCTTCTCCACTCAGCCCTTGCTGG
ACCTCAACCACACCCTCGAGTGGCCCTTGCAAGGAGTCCCCATCTCCCTGGTGATCAA
TTCCACGGGCCTGAAGGCACCCGGCCGCCTAGACTCGGTGGAGCTGGCACAAAGCTCA
GGGAAGCCCCTCCTGACTCTGCCCACGAAGCCCCTCTCCAATGGCTCCACCCATCAGC
TGTGGGGCGGGCCGCCCTTCCACACCCCCAAGGAGCGCTTCTACCTCAAGGTGAAGGG
CAAGGACCATGAGGGAAACCCCCTCCTTCGTGTCTCTGGAGTGTCCTACAGTGGGGTG
GCCCCAGGCGCTCCCCTCGTCAGCATGGCCCCCAGGATCCATGGCTACCTGCACCAGC
CCCTGCTGGTCTCCTGCTCGGTGCACAGTGCCCTTCCCTTCCGGCTGCAGCTGCGGCG
AGGTGAAGCCAGGCTGGGCGAAGAGAGGCACTTTCAGGAGTCGGGAAACAGCAGCTGG
GAGATCCTGCGGGCCTCCAAGGCCGAGGAGGGCACGTACGAGTGCACAGCCGTCAGCA
GGGCTGGGACCGGGCGAGCAAAGGCCCAGATTGTTGTCACAGACCCCCCGCCGCAGCT
GGTCCCTGCTCCCAACGTGACCGTGTCCCCAGGGGAGGCTGCCGTCCTATCCTGCCGG
GTCCTAGGCGAGGCCCCCTACAACCTGACGTGGGTCCGGGACTGGCGAGTCCTGCCGG
CCTCGACGGGCCGAGTTGCCCAGCTGGCTGACCTGTCCCTGGAGATCAGTGGCATCAT
CCCCACAGACGGCGGGAGGTACCAGTGTGTGGCCAGCAATGCCAATGGGGTCACAAGG
GCATCCGTCTGGCTCCTGGTGCGAGAGGCCCCACAGGTCAGCATCCACACCAGCTCCC
AGCACTTCTCGCAAGGTGTGGAGGTGAAGGTCAGCTGCTCAGCCTCTGGATACCCCAC
ACCCCACATCTCCTGGAGCCGTGAGAGCCAAGCCCTACAAGAGGACAGCAGAATCCAT
GTGGACGCACAGGGAACCCTGATTATTCAGGGGGTAGCCCCAGAGGATGCTGGGAATT
ACAGCTGCCAGGCGACTAATGAGGTTGGCACTGACCAGGAGACGGTCACCCTCTACTA
CACAGACCCACCGTCGGTCTCTGTCGAC ORF Start: at 1 ORF Stop: end of
sequence SEQ ID NO: 50 686 aa MW at 74232.1kD NOV9f,
KLVAVAGAPGTVMPPTTGDATLAFVFDVTGSMWDELMQVIDGASRILERSLSRRSQAI
197192443
ANYALVPFHDPDIGPVTLTADPTVFQRELRELYVQGGGDCPEMSVGAIKAAVEVANPG Protein
SFIYVFSDARAKDYHKKEELLRLLQLKQSQVVFVLTGDCGDHTHPGYLAYEEIAATSS Sequence
GQVFHLDKQQVTEVLKWVESAIQASKVHLLSTDHEEEGEHTWRLPFDPSLKEVTISLS
GPGPEIEVQDPLGRILQEDEGLNVLLNIPDSAKVVAFKPEHPGLWSIKVYSSGRHSVR
ITGVSNIDFRAGFSTQPLLDLNHTLEWPLQGVPISLVINSTGLKAPGRLDSVELAQSS
GKPLLTLPTKPLSNGSTHQLWGGPPFHTPKERFYLKVKGKDHEGNPLLRVSGVSYSGV
APGAPLVSMAFRIBGYLHQPLLVSCSVHSALPFRLQLRRGEARLGEERHFQESGNSSW
EILRASKAEEGTYECTAVSRAGTGRAKAQIVVTDFPPQLVPAPNVTVSPGEAAVLSCR
VLGEAPYNLTWVRDWRVLPASTGRVAQLADLSLEISGIIFTDGGRYQCVASNANGVTR
ASVWLLVREAPQVSIHTSSQHFSQGVEVKVSCSASGYPTPHISWSRESQALQEDSRIH
VDAQGTLIIQGVAPEDAGNYSCQATNEVGTDQETVTLYYTDPPSVSVD SEQ ID NO: 51 2058
bp NOV9g,
AAGCTTGTGGCAGTGGCCGGGGCGCCCGGGACGGTAATGCCCCCCACCACGGGGGACG
197192448
CCACCCTGGCCTTCGTCTTCGACGTCACCGGCTCCATGTGGGACGAACTGATGCAGGT DNA
GATCGATGGCGCCTCGCGCATTCTGGAACGCAGTCTGAGCCGCCGCAGCCAGGCCATC Sequence
GCCAACTACGCGCTGGTGCCCTTCCACGACCCAGATATTGGCCCAGTGACCCTCACGG
CGGACCCCACAGTGTTTCAGAGGGAGCTGAGAGAACTCTACGTGCAGGGAGGTGGTGA
CTGCCCGGAGATGAGTGTGGGGGCCATTAAGGCTGCCGTGGAGGTTGCCAACCCCGGA
TCCTTCATCTACGTCTTTTCGGATGCCCGCGCCAAAGACTATCACAAGAAGGAAGAGC
TGCTGCGGCTCCTGCAGCTCAAGCAATCACAGGTGGTCTTTGTGCTGACGGGGGACTG
TGGCGACCACACCCATCCTGGCTACCTGGCTTATGAGGAGATCGCTGCCACCAGCTCT
GGGCAGGTGTTCCACCTGGACAAGCAGCAAGTGACAGAGGTGCTGAAGTGGGTGGAGT
CAGCGATCCAGGCCTCCAAGGTGCACCTGCTGTCCACAGACCACGAGGAGGAGGGGGA
GCACACATGGAGACTCCCCTTTGACCCCAGCCTGAAGGAGGTCACCATCTCATTGAGT
GGGCCAGGGCCTGAGATTGAAGTCCAAGATCCGCTGGGGAGGATCCTGCAGGAGGACG
AGGGCCTCAACGTGCTTCTCAACATCCCTGACTCGGCCAAGGTCGTAGCCTTTAAGCC
TGAGCATCCGGGGCTGTGGTCCATCAAGGTCTATAGCAGTGGCCGCCATTCAGTGAGG
ATCACAGGCGTCAGCAACATTGACTTCCGAGCCGGCTTCTCCACTCAGCCCTTGCTGG
ACCTCAACCACACCCTCGAGTGGCCCTTGCAAGGAGTCCCCATCTCCCTGGTGATCAA
TTCCACGGGCCTGAAGGCACCCGGCCGCCTAGACTCGGTGGAGCTGGCACAAAGCTCA
GGGAAGCCCCTCCTGACTCTGCCCACGAAGCCCCTCTCCAATGGCTCCACCCATCAGC
TGTGGGGCGGGCCGCCCTTCCACACCCCCAAGGAGCGCTTCTACCTCAAGGTGAAGGG
CAAGGACCATGAGGGAAACCCCCTCCTTCGTGTCTCTGGAGTGTCCTACAGTGGGGTG
GCCCCAGGCGCTCCCCTCGTCAGCATGGCCCCCAGGATCCATGGCTACCTGCACCAGC
CCCTGCTGGTCTCCTGCTCGGTGCACAGTGCCCTTCCCTTCCGGCTGCAGCTGCGGCG
AGGTGAAGCCAGGCTGGGCGAAGAGAGGCACTTTCAGGAGTCGGGAAACAGCAGCTGG
GAGATCCTGCGGGCCTCCAAGGCCGAGGAGGGCACGTACGAGTGCACAGCCGTCAGCA
GGGCTGGGACCGGGCGAGCAAAGGCCCAGATTGTTGTCACAGACCCCCCGCCGCAGCT
GGTCCCTGCTCCCAACGTGACCGTGTCCCCAGGGGAGACTGCCGTCCTATCCTGCCGG
GTCCTAGGCGAGGCCCCCTACAACCTGACGTGGGTCCGGGACTGGCGAGTCCTGCCGG
CCTCGACGGGCCGAGTTGCCCAGCTGGCTGACCTGTCCCTGGAGATCAGTGGCATCAT
CCCCACAGACGGCGGGAGGTACCAGTGTGTGGCCAGCAATGCCAATGGGGTCACAAGG
ACATCCGTCTGGCTCCTGGTGCGAGAGGCCCCACAGGTCAGCATCCACACCAGCTCCC
AGCACTTCTCCCAAGGTGTGGAGGTGAAGGTCAGCTGCTCAGCCTCTGGATACCCCAC
ACCCCACATCTCCTGGAGCCGTGAGAGCCAAGCCCTACAAGAGGACAGCAGAATCCAT
GTGGACGCACAGGGAACCCTGATTATTCAGGGGGTAGCCCCAGAGGATGCTGGGAATT
ACAGCTGCCAGGCGACTAATGAGGTTGGCACTGACCAGGAGACGGTCACCGTCTACTA
CACAGACCCACCGTCGGTCTCTGTCGAC ORE Start: at 1 ORF Stop: end of
sequence SEQ ID NO: 52 686 aa MW at 74292.1kD NOV9g,
KLVAVAGAPGTVMPPTTGDATLAFVFDVTGSMWDELMQVIDGASRILERSLSRRSQAI
197192448
ANYALVPFHDPDIGPVTLTADPTVFQRELRELYVQGGGDCPEMSVGAIKAAVEVANPG Protein
SFIYVFSDARAKDYHKKEELLRLLQLKQSQVVFVLTGDCGDHTHPGYLAYEEIAATSS Sequence
GQVFHLDKQQVTEVLKWVESAIQASKVHLLSTDHEEEGEHTWRLPFDPSLKEVTISLS
GPGPEIEVQDPLGRILQEDEGLNVLLNIPDSAKVVAFKPEHFGLWSIKVYSSGRHSVR
ITGVSNIDFRAGFSTQPLLDLNHTLEWPLQGVPISLVINSTGLKAPGRLDSVELAQSS
GKPLLTLPTKPLSNGSTHQLWGGPPFHTPKERFYLKVKGKDHEGNPLLRVSGVSYSGV
AFGAPLVSMAPRIHGYLHQPLLVSCSVHSALPFRLQLRRGEARLGEERHFQESGNSSW
EILRASKAEEGTYECTAVSRAGTGRAKAQIVVTDPPPQLVPAPNVTVSPGETAVLSCR
VLGEAPYNLTWVRDWRVLPASTGRVAQLADLSLEISGIIPTDGGRYQCVASNANGVTR
TSVWLLVREAPQVSIHTSSQHFSQGVEVKVSCSASGYFTPHISWSRESQALQEDSRIH
VDAQGTLIIQGVAPEDAGNYSCQATNEVGTDQETVTLYYTDPPSVSVD
[0363] Sequence comparison of the above protein sequences yields
the following sequence relationships shown in Table 9B.
TABLE-US-00046 TABLE 9B Comparison of NOV9a against NOV9b through
NOV9g. Identities/ NOV9a Residues/ Similarities for the Protein
Sequence Match Residues Matched Region NOV9b 1 . . . 204 166/204
(81%) 1 . . . 204 166/204 (81%) NOV9c 80 . . . 133 15/54 (27%) 28 .
. . 71 21/54 (38%) NOV9d 20 . . . 262 217/243 (89%) 3 . . . 245
217/243 (89%) NOV9e 20 . . . 262 217/243 (89%) 3 . . . 245 217/243
(89%) NOV9f 20 . . . 262 217/243 (89%) 3 . . . 245 217/243 (89%)
NOV9g 20 . . . 262 217/243 (89%) 3 . . . 245 217/243 (89%)
[0364] Further analysis of the NOV9a protein yielded the following
properties shown in Table 9C. TABLE-US-00047 TABLE 9C Protein
Sequence Properties NOV9a PSort 0.8200 probability located in
outside; 0.1000 probability analysis: located in endoplasmic
reticulum (membrane); 0.1000 probability located in endoplasmic
reticulum (lumen); 0.1000 probability located in lysosome (lumen)
SignalP Cleavage site between residues 17 and 18 analysis:
[0365] A search of the NOV9a protein against the Geneseq database,
a proprietary database that contains sequences published in patents
and patent publication, yielded several homologous proteins shown
in Table 9D. TABLE-US-00048 TABLE 9D Geneseq Results for NOV9a
NOV9a Identities/ Residues/ Similarities for Geneseq
Protein/Organism/Length Match the Matched Expect Identifier [Patent
#, Date] Residues Region Value AAB83147 Rat secreted factor encoded
by 1 . . . 271 231/272 (84%) e-129 clone P00210D09 - Rattus sp, 275
1 . . . 272 241/272 (87%) aa. [WO200123419-A2, 05-APR- 2001]
AAY53667 Sequence gi/3328186 from an 34 . . . 262 119/234 (50%)
1e-64 alignment with protein 608 - 32 . . . 265 168/234 (70%)
Unidentified, 3117 aa. [WO9960164-A1, 25-NOV-1999] AAU75886 Human
adhesion molecule protein 34 . . . 263 72/239 (30%) 1e-21
AD4/AAD21820.1 - Homo 311 . . . 547 119/239 (49%) sapiens, 852 aa.
[WO200208423- A2, 31-JAN-2002] AAU75884 Human adhesion molecule
protein 34 . . . 263 72/239 (30%) 1e-21 AD2/G7c - Homo sapiens, 536
aa. 13 . . . 249 119/239 (49%) [WO200208423-A2, 31-JAN- 2002]
AAM79854 Human protein SEQ ID NO 3500 - 34 . . . 263 72/239 (30%)
1e-21 Homo sapiens, 836 aa. 311 . . . 547 119/239 (49%)
[WO200157190-A2, 09-AUG- 2001]
[0366] In a BLAST search of public sequence datbases, the NOV9a
protein was found to have homology to the proteins shown in the
BLASTP data in Table 9E. TABLE-US-00049 TABLE 9E Public BLASTP
Results for NOV9a NOV9a Identities/ Protein Residues/ Similarities
for Accession Match the Matched Expect Number
Protein/Organism/Length Residues Portion Value CAC37763 SEQUENCE 2
FROM PATENT 1 . . . 271 231/272 (84%) e-128 WO0123419 - Rattus
norvegicus 1 . . . 272 241/272 (87%) (Rat), 275 aa. Q96RW7
HEMICENTIN - Homo sapiens 35 . . . 262 169/228 (74%) 3e-97 (Human),
5636 aa. 38 . . . 265 199/228 (87%) T20992 hypothetical protein
F15G9.4a - 34 . . . 262 119/234 (50%) 3e-64 Caenorhabditis elegans,
5175 aa. 32 . . . 265 168/234 (70%) O76518 HEMICENTIN PRECURSOR -
34 . . . 262 119/234 (50%) 3e-64 Caenorhabditis elegans, 5198 aa.
32 . . . 265 168/234 (70%) Q96QC8 G7C PROTEIN - Homo sapiens 34 . .
. 263 72/239 (30%) 3e-21 (Human), 852 aa. 311 . . . 547 119/239
(49%)
[0367] PFam analysis predicts that the NOV9a protein contains the
domains shown in the Table 9F. TABLE-US-00050 TABLE 9F Domain
Analysis of NOV9a Identities/ Pfam NOV9a Similarities Domain Match
Region for the Matched Region Expect Value
Example 10
[0368] The NOV10 clone was analyzed, and the nucleotide and encoded
polypeptide sequences are shown in Table 10A. TABLE-US-00051 TABLE
10A NOV10 Sequence Analysis SEQ ID NO: 53 621 bp NOV10a,
ATCATGCCCCTAGGTCTCCTGTGGCTGGGCCTAGCCCTGTTGGGGGCTCTGCATGCCC
CG102942-01
AGGCCCAGGACTCCACCTCAGACCTGATCCCAGCCCCACCTCTGAGCAAGGTCCCTCT DNA
GCAGCAGAACTTCCAGGACAACCAATTCCAGGGGAAGTGGTATGTGGTAGGCCTGGCA Sequence
GGGAATGCAATTCTCAGAGAAGACAAAGACCCGCAAAAGATGTATGCCACCATCTATG
AGCTGAAAGAAGACAAGAGCTACAATGTCACCTCCGTCCTGTTTAGGAAAAAGAAGTG
TGACTACTGGATCAGGACTTTTGTTCCAGGTTGCCAGCCCGGCGAGTTCACGCTGGGC
AACATTAAGAGTTACCCTGGATTAACGAGTTACCTCGTCCGAGTGGTGAGCACCAACT
ACAACCAGCATGCTATGGTGTTCTTCAAGAAAGTTTCTCAAAACAGGGAGTACTTCAA
GATCACCCTCTACGGTAGAACCAAGGAGCTGACTTCGGAACTAAAGGAGAACTTCATC
CGCTTCTCCAAATCTCTGGGCCTCCCTGAAAACCACATCGTCTTCCCTGTCCCAATCG
GTAATGGCCAGTCTGGATGAGGGGACGGGGACATGGGGACT ORF Start: ATG at 4 ORF
Stop: TGA at 598 SEQ ID NO: 54 198 aa MW at 22456.7kD NOV10a,
MPLGLLWLGLALLGALHAQAQDSTSDLIPAPPLSKVPLQQNFQDNQFQGKWYVVGLAG
CG102942-01
NAILREDKDPQKMYATIYELKEDKSYNVTSVLFRKKKCDYWIRTFVPGCQPGEFTLGN Protein
IKSYPGLTSYLVRVVSTNYNQHANVFFKKVSQNREYFKITLYGRTKELTSELKENFIR Sequence
FSKSLGLPENHIVFPVPIGNGQSG SEQ ID NO: 55 609 bp NOV10b
ATCATGCCCCTAGGTCTCCTGTGGCTGGGCCTAGCCCTGTTGGGGGCTCTGCATGCCC
CG102942-03
AGGCCCAGGACTCCACCTCAGACCTGATCCCAGCCCCACCTCTGAGCAAGGTCCCTCT DNA
GCAGCAGAACTTCCAGGACAACCAATTCCAGGGGAAGTGGTATGTGGTAGGCCTGGCA Sequence
GGGAATGCAATTCTCAGAGAAGACAAAGACCCGCAAAAGATGTATGCCACCATCTATG
AGCTGAAAGAAGACAAGAGCTACAATGTCACCTCCGTCCTGTTTAGGAAAAAGAAGTG
TGACTACTGGATCAGGACTTTTGTTCCAGGTTGCCAGCCCGGCGAGTTCACGCTGGGC
AACATTAAGAGTTACCCTGGATTAACGAGTTACCTCGTCCGAGTGGTGAGCACCAACT
ACAACCAGCATGCTATGGTGTTCTTCAAGAAAGTTTCTCAAAACAGGGAGTACTTCAA
GATCACCCTCTACGGGAGAACCAAGGAGCTGACTTCGGAACTAAAGGAGAACTTCATC
CGCTTCTCCAAATCTCTGGGCCTCCCTGAAAACCACATCGTCTTCCCTGTCCCAATCG
GTAATGGCCAGTCTGGATGAGGGGACGGG ORF Start: ATG at 4 ORE Stop: TGA at
598 SEQ ID NO: 56 198 aa MW at 22456.7kD NOV10b,
MPLGLLWLGLALLGALHAQAQDSTSDLIPAPPLSKVPLQQNFQDNQFQGKWYVVGLAG
CG102942-03
NAILREDKDPQKMYATIYELKEDKSYNVTSVLFRKKKCDYWIRTFVPGCQPGEFTLGN Protein
IKSYPGLTSYLVRVVSTNYNQHANVFFKKVSQNREYFKITLYGRTKELTSELKENFIR Sequence
FSKSLGLPENHIVFPVPIGNGQSG SEQ ID NO: 57 477bp NOV10c,
CGCGGATCCCAATTCCAGGGGAAGTGGTATGTGGTAGGCCTGGCAGGGAATGCAATTC
237376776
TCAGAGGAGACAAAGACCCGCAAAAGATGTATGCCACCATCTATGAGCTGAAAGAAGA DNA
CAAGAGCTACAATGTCACCTCCGTCCTGTTTAGGAAAAAGAAGTGTGACTACTGGATC Sequence
AGGACTTTTGTTCCAGGTTGCCAGCCCGGCGAGTTCACGCTGGGCAACATTAAGAGTT
ACCCTGGATTAACGAGTTACCTCGTCCGAGTGGTGAGCACCAACTACAACCAGCATGC
TATGGTGTTCTTCAAGAAAGTTTCTCAAAACAGGGAGTACTTCAAGATCACCCTCTAC
GGGAGAACCAAGGAGCTGACTTCGGAACTAAAGGAGAACTTCATCCGCTTCTCCAAAT
CTCTGGGCCTCCCTGAAAACCACATCGTCTTCCCTGTCCCAATCGGTAATGGCCAGTC
TGGACTCGAGGCG ORF Start: at 1 ORF Stop: end of sequence +TL,44 SEQ
ID NO: 58 159 aa MW at 18222.8kD NOV10c,
RGSQFQGKWYVVGLAGNAILRGDKDPQKMYATIYELKEDKSYNVTSVLFRKKKCDYWI
237376776
RTFVPGCQPGEFTLGNIKSYPGLTSYLVRVVSTNYNQHANVFFKKVSQNREYFKITLY Protein
GRTKELTSELKENFIRFSKSLGLPENHIVFPVPIGNGQSGLEA Sequence
[0369] Sequence comparison of the above protein sequences yields
the following sequence relationships shown in Table 10B.
TABLE-US-00052 TABLE 10B Comparison of NOV10a against NOV10b and
NOV10c. Identities/ NOV10a Residues/ Similarities for Protein
Sequence Match Residues the Matched Region NOV10b 19 . . . 198
180/180 (100%) 19 . . . 198 180/180 (100%) NOV10c 45 . . . 198
152/154 (98%) 3 . . . 156 153/154 (98%)
[0370] Further analysis of the NOV10a protein yielded the following
properties shown in Table 10C. TABLE-US-00053 TABLE 10C Protein
Sequence Properties NOV10a PSort 0.4658 probability located in
outside; 0.1134 probability analysis: located in microbody
(peroxisome); 0.1000 probability located in endoplasmic reticulum
(membrane); 0.1000 probability located in endoplasmic reticulum
(lumen) SignalP Cleavage site between residues 21 and 22
analysis:
[0371] A search of the NOV10a protein against the Geneseq database,
a proprietary database that contains sequences published in patents
and patent publication, yielded several homologous proteins shown
in Table 10D. TABLE-US-00054 TABLE 10D Geneseq Results for NOV10a
NOV10a Identities/ Residues/ Similarities for Geneseq
Protein/Organism/Length Match the Matched Expect Identifier [Patent
#, Date] Residues Region Value AAG74315 Human colon cancer antigen
1 . . . 192 192/192 (100%) e-110 protein SEQ ID NO: 5079 - 57 . . .
248 192/192 (100%) Homo sapiens, 254 aa. [WO200122920-A2,
05-APR-2001] AAY71470 Human neutrophil gelatinase 1 . . . 192
192/192 (100%) e-110 associated protein (NGAL) - 1 . . . 192
192/192 (100%) Homo sapiens, 198 aa. [WO200029576-A1, 25-MAY-2000]
AAB43668 Human cancer associated protein 1 . . . 192 192/192 (100%)
e-110 sequence SEQ ID NO: 1113 - 57 . . . 248 192/192 (100%) Homo
sapiens, 254 aa. [WO200055350-A1, 21-SEP-2000] AAW49088 Human NGAL
protein - Homo sapiens, 1 . . . 192 189/192 (98%) e-107 197 aa.
[WO9830907-A1, 16-JUL-1998] 1 . . . 191 190/192 (98%) AAW18203
Human NGAL protein - Homo sapiens, 1 . . . 192 189/192 (98%) e-107
197 aa. [U.S. Pat. No. 5627034-A, 06-MAY-1997] 1 . . . 191 190/192
(98%)
[0372] In a BLAST search of public sequence datbases, the NOV10a
protein was found to have homology to the proteins shown in the
BLASTP data in Table 10E. TABLE-US-00055 TABLE 10E Public BLASTP
Results for NOV10a NOV10a Identities/ Protein Residues/
Similarities for Accession Match the Matched Expect Number
Protein/Organism/Length Residues Portion Value P80188 Neutrophil
gelatinase-associated 1 . . . 192 192/192 (100%) e-110 lipocalin
precursor (NGAL) (P25) 1 . . . 192 192/192 (100%) (25 kDa
alpha-2-microglobulin- related subunit of MMP-9) (Lipocalin 2)
(Oncogene 24p3) - Homo sapiens (Human), 198 aa. JC2339 neutrophil
gelatinase-associated 1 . . . 192 189/192 (98%) e-107 lipocalin
precursor - human, 197 aa. 1 . . . 191 190/192 (98%) Q9QVP7
NEU-RELATED LIPOCALIN - 1 . . . 191 121/191 (63%) 1e-66 Rattus sp,
198 aa. 1 . . . 191 150/191 (78%) P30152 Neutrophil
gelatinase-associated 1 . . . 191 120/191 (62%) 1e-65 lipocalin
precursor (NGAL) (P25) 1 . . . 191 148/191 (76%)
(Alpha-2-microglobulin-related protein) (Alpha-2U globulin- related
protein) (Lipocalin 2) - Rattus norvegicus (Rat), 198 aa. Q60842
CHROMOSOME 24P3 - Mus musculus 1 . . . 194 119/196 (60%) 3e-64
(Mouse), 283 aa (fragment). 8 . . . 203 154/196 (77%)
[0373] PFam analysis predicts that the NOV10a protein contains the
domains shown in the Table 10F. TABLE-US-00056 TABLE 10F Domain
Analysis of NOV10a Identities/ Pfam NOV10a Similarities for Expect
Domain Match Region the Matched Region Value lipocalin 46 . . . 189
42/152 (28%) 5.4e-34 115/152 (76%)
Example 11
[0374] The NOV11 clone was analyzed, and the nucleotide and encoded
polypeptide sequences are shown in Table 11A. TABLE-US-00057 TABLE
11A NOV11 Sequence Analysis SEQ ID NO: 59 2210 bp NOV11a,
ATGACAATTTTAAGAGTGTTTAACCAAGACTGTTCCTTTAAATGTGTTCTTTTGCTGC
CG104016-01
TGTTTAATTATACATGTCAATTATTTACAGATCCTGTGGTATTGTGGAAATTCCCAGA DNA
GGACTTTGGAGACCAGGAAATACTACAGAGTGTGCCAAAGTTCTGTTTTCCCTTTGAC Sequence
GTTGAAAGGTACAGTATAAGTCAAGTTGGACAGCACTTTACCTTTGTACTGACAGACA
TTGAAAGTAAACAGAGATTTGGATTCTGCAGACTGACGTCAGGAGGCACAATTTGTTT
ATGCATCCTTAGTTACCTTCCCTGGTTTGAAGTGTATTACAAGCTTCTAAATACTCTT
GCAGATTACTTGGCTAAGCATTCCTACTTCATTGCCCCTGATGTAACTGGACTCCCAA
CAATACCCGAGAGTAGAAATCTTACAGAATATTTTGTTGCCGTGGATGTGAACAACAT
GCTGCAGCTGTATGCCAGTATGCTGCATGAAAGGCGCATCGTGATTATCTCGAGCAAA
TTAAGCACTTTAACTGCCTGTATCCATGGATCAGCTGCTCTTCTATACCCAATGTATT
GGCAACACATATACATCCCAGTGCTTCCTCCACACCTGCTGGACTACTGCAGTGCCCC
AATGCCATACCTGATTGGAATACACTCCAGCCTCATAGAGAGAGTGAAAAACAAATCA
TTGGAAGATGTTGTTATGTTAAATGTTGATACAAACACATTAGAATCACCATTTAGTG
ACTTGAACAACCTACCAAGTGATGTGGTAAGTGCCTTGAAAAATAAACTGAAGAAGCA
GTCTACAGCTACGGGTGATGGAGTAGCTAGGGCCTTTCTTAGAGCACAGGCTGCTTTG
TTTGGATCCTACAGAGATGCACTGAGATACAAACCTGGTGAGCCCATCACTTTCTGTG
AGGAGAGTTTTGTAAAGCACCGCTCAAGCGTGATGAAACAGTTCCTGGAAACTGCCAT
TAACCTCCAGCTTTTTAAGCAGGTATTTATCGATGGTCGACTGGCAAAACTAAATGCA
GGAAGGGGTTTCTCTGATGTATTTGAAGAAGAGATCACTTCAGGTGGCTTTTGTGGAG
GTAAAGACAAGTTACAATATAAATATGTTTCTGTTTTTCTTTTGCAGAAAGGAGGTGC
ACTGTTCAACACAGCAATGACCAAAGCAACCCCTGCTGTACGGACAGCATATAAATTT
GCAAAAAATCATGCAAAGCTGGGACTAAAGGAAGTGAAGAGTAAACTAAAACACAAGG
AAAATGAAGAAGATTATGGGACCTGTTCTAGTTCTGTACAATATACACCAGTTTACAA
ATTACACAATGAAAAGGGAGGAAACTCAGAAAAGCGTAAGCTTGCTCAGGCACGCTTA
AAAAGGCCTCTTAAGAGCCTTGATGGTGCTCTATATGATGATGAAGATGATGATGACA
TTGAAAGAGCAAGCAAGTTATCTTCTGAAGATGGTGAAGAAGCTTCTGCTTATCTCTA
TGAGAGTGATGACTCTGTTGAAACAAGAGTGAAGACTCCTTACTCAGGTGAAATGGAC
TTACTAGGAGAGATTCTTGATACATTGAGCACACACAGCTCAGATCAGGGGAAGCTGG
CAGCTGCAAAGAGCTTGGATTTCTTTAGATCAATGGATGACATTGATTACAAACCTAC
GAATAAATCTAATGCTCCTAGTGAGAATAACCTGGCTTTCCTCTGTGGTGGTTCTGGT
GACCAAGCAGAGTGGAATCTTGGGCAAGACGATAGTGCCCTCCATGGCAAACACCTCC
CTCCATCTCCTAGGAAGCGGGTTTCCTCTAGTGGTTTGACAGATTCTCTGTTTATCCT
GAGAGAGGAAAACAGTAACAAGCACCTCGGTGCTGACAATGTGAGTGACCCTACTTCA
GGACTGGATTTCCAACTCACTTCCCCTGAAGTTTCCCAGACTGATAAAGGAAAAACAG
AAAAGAGGGAAACACTAAGCCAGATTTCAGATGATCTGCTTATACCCGGTCTTGGGCG
GCATTCATCGACTTTTGTTCCTTGGGAGAAAGAAGGGAAAGAAGCCAAAGAGACTTCA
GAAGATATTGGACTGCTCCATGAAGTAGTGTCATTATGTCATATGACATCTGACTTCC
AACAAAGCTTGAACATTTCAGACAAAAACACAAATGGAAACCAAACTTAAATCTTGCA TCCAAG
ORF Start: ATG at 1 ORF Stop: TAA at 2194 SEQ ID NO: 60 731 aa MW
at 81769.5kD NOV11a,
MTILRVFNQDCSFKCVLLLLFNYTCQLFTDPVVLWKFPEDFGDQEILQSVPKFCFFFD
CG104016-01
VERYSISQVGQHFTFVLTDIESKQRFGFCRLTSGGTICLCILSYLPWFEVYYKLLNTL Protein
ADYLAKHSYFIAPDVTGLPTIPESRNLTEYFVAVDVNNMLQLYASMLHERRIVIISSK Sequence
LSTLTACIHGSAALLYPMYWQHIYIPVLFPHLLDYCSAPMPYLIGIHSSLIERVKNKS
LEDVVMLNVDTNTLESPFSDLNNLPSDVVSALKNKLKKQSTATGDGVARAFLRAQAAL
FGSYRDALRYKPGEPITFCEESFVKHRSSVMKQFLETAINLQLFKQVFIDGRLAKLNA
GRGFSDVFEEEITSGGFCGGKDKLQYKYVSVFLLQKGGALFNTAMTKATPAVRTAYKF
AKNHAKLGLKEVKSKLKHKENEEDYGTCSSSVQYTPVYKLHNEKGGNSEKRKLAQARL
KRPLKSLDGALYDDEDDDDIERASKLSSEDGEEASAYLYESDDSVETRVKTPYSGEMD
LLGEILDTLSTHSSDQGKLAAAKSLDFFRSMDDIDYKPTNKSNAPSENNLAFLCGGSG
DQAEWNLGQDDSALHGKHLPPSPRKRVSSSGLTDSLFILREENSNKHLGADNVSDPTS
GLDFQLTSPEVSQTDKGKTEKRETLSQISDDLLIPGLGRHSSTFVPWEKEGKEAKETS
EDIGLLHEVVSLCHMTSDFQQSLNISDKNTNGNQT SEQ ID NO: 61 2256 bp NOV11b,
AGATCTGATCCTGTGGTATTGTGGAAATTCCCAGAGGACTTTGGAGACCAGGAAATAC
197208336
TACAGAGTGTGCCAAAGTTCTGTTTTCCCTTTGACGTTGAAAGGGTGTCTCAGAATCA DNA
AGTTGGACAGCACTTTACCTTTGTACTGACAGACATTGAAAGTAAACAGAGATTTGGA Sequence
TTCTGCAGACTGACGTCAGGAGGCACAATTTGTTTATGCATCCTTAGTTACCTTCCCT
GGTTTGAAGTGTATTACAAGCTTCTAAATACTCTTGCAGATTACTTGGCTAAGGAACT
GGAAAATGATTTGAATGAAACTCTCAGATCACTGTATAACCACCCAGTACCAAAGGCA
AATACTCCTGTAAATTTGAGTGTGAACCAAGAGATATTTATTACCTGTGAGCAAGTTC
TGAAAGATCAGCCTGCTCTACTACCGCATTCCTACTTCATTGCCCCTGATGTAACTGG
ACTCCCAACAATACCCGAGAGTAGAAATCTTACAGAATATTTTGTTGCCGTGGATGTG
AACAACATGCTGCAGCTGTATGCCAGTATGCTGCATGAAAGGCGCATCGTGATTATCT
CGAGCAAATTAAGCACTTTAACTGCCTGTATCCATGGATCAGCTGCTCTTCTATACCC
AATGTATTGGCAACACATATACATCCCAGTGCTTCCTCCACACCTGCTGGACTACTGC
TGTGCCCCAATGCCATACCTGATTGGAATACACTCCAGCCTCATAGAGAGAGTGAAAA
ACAAATCATTGGAAGATGTTGTTATGTTAAATGTTGATACAAACACATTAGAATCACC
ATTTAGTGACTTGAACAACCTACCAAGTGATGTGGTCTCGGCCTTGAAAAATAAACTG
AAGAAGCAGTCTACAGCTACGGGTGATGGAGTAGCTAGGGCCTTTCTTAGAGCACAGG
CTGCTTTGTTTGGATCCTACAGAGATGCACTGAGATACAAACCTGGTGAGCCCATCAC
TTTCTGTGAGGAGAGTTTTGTAAAGCACCGCTCAAGCGTGATGAAACAGTTCCTGGAA
ACTGCCATTAACCTCCAGCTTTTTAAGCAGTTTATCGATGGTCGACTGGCAAAACTAA
ATGCAGGAAGGGGTTTCTCTGATGTATTTGAAGAAGAGATCACTTCAGGTGGCTTTTG
TGGAGGGAACCCGAGGTCATATCAACAATGGGTGCATACAGTCAAGAAAGGAGGTGCA
CTGTTCAACACAGCAATGACCAAAGCAACCCCTGCTGTACGGACAGCATATAAATTTG
CAAAAAATCATGCAAAGCTGGGACTAAAGGAAGTGAAGAGTAAACTAAAACACAAGGA
AAATGAAGAAGATTATGGGACCTGTTCTAGTTCTGTACAATATACACCAGTTTACAAA
TTACACAATGAAAAGGGAGGAAACTCAGAAAAGCGTAAGCTTGCTCAGGCACGCTTAA
AAAGGCCTCTTAAGAGCCTTGATGGTGCTCTATATGATGATGAAGATGATGATGACAT
TGAAAGAGCAAGCAAGTTATCTTCTGAAGATGGTGAAGAAGCTTCTGCTTATCTCTAT
GAGAGTGATGACTCTGTTGAAACAAGAGTGAAGACTCCTTACTCAGGTGAAATGGACT
TACTAGGAGAGATTCTTGATACATTGAGCACACACAGCTCAGATCAGGGGAGGCTGGC
AGCTGCAAAGAGCTTGGATTTCTTTAGATCAATGGACGACATTGATTACAAACCTACG
AATAAATCTAATGCTCCTAGTGAGAATAACCTGGCTTTCCTCTGTGGTGGTTCTGGTG
ACCAAGCAGAGTGGAATGTTGGGCAAGACGATAGTGCCCTCCATGGCAAACACCTCCC
TCCATCTCCTAGGAAGCGGGTTTCCTCTAGTGGTTTGACAGATTCTCTGTTTATCCTG
AAAGAGGAAAACAGTAACAAGCACCTCGGTGCTGACAATGTGAGTGACCCTACTTCAG
GACTGGATTTCCAACTCACTTCCCCTGAAGTTTCCCAGACTGATAAAGGAAAAACAGA
AAAGAGGGAAACACTAAGCCAGATTTCAGATGATCTGCTTATACCCGGTCTTGGGCGG
CATTGATCGACTTTTGTTCCTTGGGAGAAAGAAGGGAAAGAAGCCAAAGAGACTTCAG
AAGATATTGGACTGCTCCATGAAGTAGTGTCATTATGTCATATGACATCTGACTTCCA
ACAAAGCTTGAACATTTCAGACAAAAACACAAATGGAAACCAAACTAGATCT ORF Start: at
1 ORF Stop: end of sequence SEQ ID NO: 62 752 aa MW at 84005.6kD
NOV11b, RSDPVVLWKFPEDFGDQEILQSVPKFCFPFDVERVSQNQVGQHFTFVLTDIESKQRFG
197208336
FCRLTSGGTICLCILSYLPWFEVYYKLLNTLADYLAKELENDLNETLRSLYNHFVPKA Protein
NTPVNLSVNQEIFITCEQVLKDQPALLPHSYFIAPDVTGLPTIPESRNLTEYFVAVDV Sequence
NNMLQLYASMLHERRIVIISSKLSTLTACIHGSAALLYPMYWQHIYIPVLPPHLLDYC
CAPMPYLIGIHSSLIERVKNKSLEDVVMLNVDTNTLESPFSDLNNLPSDVVSALKNKL
KKQSTATGDGVARAFLRAQAALFGSYRDALRYKPGEPITFCEESFVKHRSSVMKQFLE
TAINLQLFKQFIDGRLAKLNAGRGFSDVFEEEITSGGFCGGNPRSYQQWVHTVKKGGA
LFNTAMTKATPAVRTAYKFAKNHAKLGLKEVKSKLKHKENEEDYGTCSSSVQYTPVYK
LHNEKGGNSEKRKLAQARLKRPLKSLDGALYDDEDDDDIERASKLSSEDGEEASAYLY
ESDDSVETRVKTPYSGEMDLLGEILDTLSTHSSDQGRLAAAKSLDFFRSMDDIDYKPT
NKSNAPSENNLAFLCGGSGDQAEWNLGQDDSALHGKHLPPSPRKRVSSSGLTDSLFIL
KEENSNKHLGADNVSDPTSGLDFQLTSPEVSQTDKGKTEKRETLSQISDDLLIPGLGR
HSSTFVPWEKEGKEAKETSEDIGLLHEVVSLCHMTSDFQQSLNISDKNTNGNQTRS SEQ ID NO:
63 2256 bp NOV11c,
AGATCTGATCCTGTGGTATTGTGGAAATTCCCAGAGGACTTTGGAGACCAGGAAATAC
197306179
TACAGAGTGTGCCAAAGTTCTGTTTTCCCTTTGACGTTGAAAGGGTGTCTCAGAATCA DNA
AGTTGGACAGCACTTTACCTTTGTACTGACAGACATTGAAAGTAAACAGAGATTTGGA Sequence
TTCTGCAGACTGACGTCAGGAGGCACAATTTGTTTATGCATCCTTAGTTACCTTCCCT
GGTTTGAAGTGTATTACAAGCTTCTAATACTCTTGCAGATTACCTTGGCTAAGGAACT
GGAAAATGATTTGAATGAAACTCTCAGATCACTGTATAACCACCCAGTACCAAAGGCA
AATACTCCTGTAAATTTGAGTGTGAACCAAGAGATATTTATTACCTGTGAGCAAGTTC
TGAAAGATCAGCCTGCTCTACTACCGCATTCCTACTTCATTGCCCCTGATGTAACTGG
ACTCCCAACAATACCCGAGAGTAGAAATCTTACAGAATATTTTGTTGCCGTGGATGTG
AACAACATGCTGCAGCTGTATGCCAGTATGCTGCATGAAAGGCGCATCGTGATTATCT
CGAGCAAATTAAGCACTTTAACTGCCTGTATCCATGGATCAGCTGCTCTTCTATACCC
AATGTATTGGCAACACATATACATCCCAGTGCTTCCTCCACACCTGCTGGACTACTGC
TGTGCCCCAATGCCATACCTGATTGGAATACACTCCAGCCTCATAGAGAGAGTGAAAA
ACAAATCATTGGAAGATGTTGTTATGTTAAATGTTGATACAAACACATTAGAATCACC
ATTTAGTGACTTGAACAACCTACCAAGTGATGTGGTCTCGGCCTTGAAAAATAAACTG
AAGAAGCAGTCTACAGCTACGGGTGATGGAGTAGCTAGGGCCTTTCTTAGAGCACAGG
CTGCTTTGTTTGGATCCTACAGAGATGCACTGAGATACAAACCTGGTGAGCCCATCAC
TTTCTGTGAGGAGAGTTTTGTAAAGCACCGCTCAAGCGTGATGAAACAGTTCCTGGAA
ACTGCCATTAACCTCCAGCTTTTTAAGCAGTTTATCGATGGTCGACTGGCAAAACTAA
ATGCAGGAAGGGGTTTCTCTGATGTATTTGAAGAAGAGATCACTTCAGGTGGCTTTTG
TGGAGGGAACCCGAGGTCATATCAACAATGGGTGCATACAGTCAAGAAAGGAGGTGCA
CTGTTCAACACAGCAATGACCAAAGCAACCCCTGCTGTACGGACAGCATATAAATTTG
CAAAAAATCATGCAAAGCTGGGACTAAAGGAAGTGAAGAGTAAACTAAAACACAAGGA
AAATGAAGAAGATTATGGGACCTGTTCTAGTTCTGTACAATATACACCAGTTTACAAA
TTACACAATGAAAAGGGAGGAAACTCAGAAAAGCGTAAGCTTGCTCAGGCACGCTTAA
AAAGGCCTCTTAAGAGCCTTGATGGTGCTCTATATGATGATGAAGATGATGATGACAT
TGAAAGAGCAAGCAAGTTATCTTCTGAAGATGGTGAAGAAGCTTCTGCTTATCTCTAT
GAGAGTGATGACTCTGTTGAAACAAGAGTGAAGACTCCTTACTCAGGTGAAATGGACT
TACTAGGAGAGATTCTTGATACATTGAGCACACACAGCTCAGATCAGGGGAGGCTGGC
AGCTGCAAAGAGCTTGGATTTCTTTAGATCAATGGACGACATTGATTACAAACCTACG
AATAAATCTAATGCTCCTAGTGAGAATAACCTGGCTTTCCTCTGTGGTGGTTCTGGTG
ACCAAGCAGAGTGGAATCTTGGGCAAGACGATAGTGCCCTCCATGGCAAACACCTCCC
TCCATCTCCTAGGAAGCGGGTTTCCTCTAGTGGTTTGACAGATTCTCTGTTTATCCTG
AAAGAGGAAAACAGTAACAAGCACCTCGGTGCTGACAATGTGAGTGACCCTACTTCAG
GACTGGATTTCCAACTCACTTCCCCTGAAGTTTCCCAGACTGATAAAGGAAAAACAGA
AAAGAGGGAAACACTAAGCCAGATTTCAGATGATCTGCTTATACCCGGTCTTGGGCGG
CATTCATCGACTTTTGTTCCTTGGGAGAAAGAAGGGAAAGAAGCCAAAGAGACTTCAG
AAGATATTGGACTGCTCCATGAAGTAGTGTCATTATGTCATATGACATCTGACTTCCA
ACAAAGCTTGAACATTTCAGACAAAAACACAAATGGAAACCAAACTAGATCT ORF Start: at
1 ORF Stop: end of sequence SEQ ID NO: 64 752 aa MW at 84005.6kD
NOV11c, RSDPVVLWKFPEDFGDQEILQSVPKFCFPFDVERVSQNQVGQHFTFVLTDIESKQRFG
197306179
FCRLTSGGTICLCILSYLPWFEVYYKLLNTLADYLAKELENDLNETLRSLYNHPVPKA Protein
NTPVNLSVNQEIFITCEQVLKDQFALLPHSYFIAPDVTGLFTIPESRNLTEYFVAVDV Sequence
NNMLQLYASMLHERRIVIISSKLSTLTACIHGSAALLYPMYWQHIYIPVLPPHLLDYC
CAPMPYLIGIHSSLIERVKNKSLEDVVMLNVDTNTLESPFSDLNNLPSDVVSALKNKL
KKQSTATGDGVARAFLRAQAALFGSYRDALRYKPGEPITFCEESFVKHRSSVMKQFLE
TAINLQLFKQFIDGRLAKLNAGRGFSDVFEEEITSGGFCGGNPRSYQQWVHTVKKGGA
LFNTAMTKATPAVRTAYKFAKNHAKLGLKEVKSKLKHKENEEDYGTCSSSVQYTPVYK
LHNEKGGNSEKRKLAQARLKRPLKSLDGALYDDEDDDDIERASKLSSEDGEEASAYLY
ESDDSVETRVKTPYSGEMDLLGEILDTLSTHSSDQGRLAAAKSLDFFRSMDDIDYKPT
NKSNAPSENNLAFLCGGSGDQAEWNLGQDDSALHGKHLPPSPRKRVSSSGLTDSLFIL
KEENSNKHLGADNVSDPTSGLDFQLTSPEVSQTDKGKTEKRETLSQISDDLLIPGLGR
HSSSTFVPWEKEGKEAKETSEDIGLLHEVVSLCHMTSDFQQSLNISDKNTNGNQTRS SEQ ID
NO: 65 2259 bp NOV11d,
AGATCTGATCCTGTGGTATTGTGGAAATTCCCAGAGGACTTTGGAGACCAGGAAATAC
219903686
TACAGAGTGTGCCAAAGTTCTGTTTTCCCTTTGACGTTGAAAGGGTGTCTCAGAATCA DNA
AGTTGGACAGCACTTTACCTTTGTACTGACAGACATTGAAAGTAAACAGAGATTTGGA Sequence
TTCTGCAGACTGACGTCAGGAGGCACAATTTGTTTATGCATCCTTAGTTACCTTCCCT
GGTTTGAAGTGTATTACAAGCTTCTAAATACTCTTGCAGATTACTTGGCTAAGGAACT
GGAAAATGATTTGAATGAAACTCTCAGATCACTGTATAACCACCCAGTACCAAAGGCA
AATACTCCTGTAAATTTGAGTGTGAACCAAGAGATATTTATTGCCTGTGAGCAAGTTC
TGAAAGATCAGCCTGCTCTAGTACCGCATTCCTACTTCATTGCCCCTGATGTAACTGG
ACTCCCAACAATACCCGAGAGTAGAAATCTTACAGAATATTTTGTTGCCGTGGATGTG
AACAACATGCTGCAGCTGTATGCCAGTATGCTGCATGAAAGGCGCATCGTGATTATCT
CGAGCAAATTAAGCACTTTAACTGCCTGTATCCATGGATCAGCTGCTCTTCTATACCC
AATGTATTGGCAACACATATACATCCCAGTGCTTCCTCCACACCTGCTGGACTACTGC
TGTGCCCCAATGCCATACCTGATTGGAATACACTCCAGCCTCATAGAGAGAGTGAAAA
ACAAATCATTGGAAGATGTTGTTATGTTAAATGTTGATACAAACACATTAGAATCACC
ATTTAGTGACTTGAACAACCTACCAAGTGATGTGGTCTCGGCCTTGAAAAATAAACTG
AAGAAGCAGTCTACAGCTACGGGTGATGGAGTAGCTAGGGCCTTTCTTAGAGCACAGG
CTGCTTTGTTTGGATCCTACAGAGATGCACTGAGATACAAACCTGGTGAGCCCATCAC
TTTCTGTGAGGAGAGTTTTGTAAAGCACCGCTCAAGCGTGATGAAACAGTTCCTGGAA
ACTGCCATTAACCTCCAGCTTTTTAAGCAGTTTATCGATGGTCGACTGGCAAAACTAA
ATGCAGGAAGGGGTTTCTCTGATGTATTTGAAGAAGAGATCACTTCAGGTGGCTTTTG
TGGAGGGAACCCGAGGTCATATCAACAATGGGTGCATACAGTCAAGAAAGGAGGTGCA
CTGTTCAACACAGCAATGACCAAAGCAACCCCTGCTGTACGGACAGCATATAAATTTG
CAAAAAATCATGCAAAGCTGGGACTAAAGGAAGTGAAGAGTAAACTAAAACACAAGGA
AAATGAAGAAGATTATGGGACCTGTTCTAGTTCTGTACAATATACACCAGTTTACAAA
TTACACAATGAAAAGGGAGGAAACTCAGAAAAGCGTAAGCTTGCTCAGGCACGCTTAA
AAAGGCCTCTTAAGAGCCTTGATGGTGCTCTATATGATGATGAAGATGATGATGACAT
TGAAAGAGCAAGCAAGTTATCTTCTGAAGATGGTGAAGAAGCTTCTGCTTATCTCTAT
GAGAGTGATGACTCTGTTGAAACAAGAGTGAAGACTCCTTACTCAGGTGAAATGGACT
TACTAGGAGAGATTCTTGATACATTGAGCACACACAGCTCAGATCAGGGGAAGCTGGC
AGCTGCAAAGAGCTTGGATTTCTTTAGATCAATGGATGACATTGATTACAAACCTACG
AATAAATCTAATGCTCCTAGTGAGAATAACCTGGCTTTCCTCTGTAGTGGTTCTGGTG
ACCAAGCAGAGTGGAATCTTGGGCAAGACGATAGTGCCCTCCATGGCAAACACCTCCC
TCCATCTCCTAGGAAGCGGGTTTCCTCTAGTGGTTTGACAGATTCTCTGTCTATCCTG
AAAGAGGAAAACAGTAACAAGCACCTCGGTGCTGACAATGTGAGTGACCCTACTTCAG
GACTGGATTTCCAACTCACTTCCCCTGAAGTTTCCCAGACTGATAAAGGAAAAACAGA
AAAGAGGGAAACACTAAGCCAGATTTCAGATGATCTGCTTATACCCGGTCTTGGGCGG
CATTCATCGACTTTTGTTCCTTGGGAGAAAGAAGGGAAAGAAGCCAAAGAGACTTCAG
AAGATATTGGACTGCTCCATGAAGTAGTGTCATTATGTCATATGACATCTGACTTGCA
AGCTAAAGCTTGGAACATTTCAGACAAAAACACAAATGGAAACCAAACTAGATCT ORF Start:
at 1 ORF Stop: end of sequence SEQ ID NO: 66 753 aa MW at 84031.7kD
NOV11d, RSDPVVLWKFPEDFGDQEILQSVPKFCFPFDVERVSQNQVGQHFTFVLTDIESKQRFG
219903686
FCRLTSGGTICLCILSYLPWFEVYYKLLNTLADYLAKELENDLNETLRSLYNHPVPKA Protein
NTPVNLSVNQEIFIACEQVLKDQPALVPHSYFIAFDVTGLFTIPESRNLTEYFVAVDV Sequence
NNMLQLYASMLHERRIVIISSKLSTLTACIHGSAALLYPMYWQHIYIPVLPPHLLDYC
CAPMPYLIGIHSSLIERVKNKSLEDVVMLNVDTNTLESPFSDLNNLPSDVVSALKNKL
KKQSTATGDGVARAFLRAQAALFGSYRDALRYKPGEPITFCEESFVKHRSSVMKQFLE
TAINLQLFKQFIDGRLAKLNAGRGFSDVFEEEITSGGFCGGNPRSYQQWVHTVKKGGA
LFNTAMTKATPAVRTAYKFAKNHAKLGLKEVKSKLKHKENEEDYGTCSSSVQYTPVYK
LHNEKGGNSEKRKLAQARLKRPLKSLDGALYDDEDDDDIERASKLSSEDGEEASAYLY
ESDDSVETRVKTPYSGEMDLLGEILDTLSTHSSDQGKLAAAKSLDFFRSMDDIDYKPT
NKSNAPSENNLAFLCSGSGDQAEWNLGQDDSALHGKHLPPSPRKRVSSSGLTDSLSIL
KEENSNKHLGADNVSDPTSGLDFQLTSPEVSQTDKGKTEKRETLSQISDDLLIPGLGR
HSSTFVPWEKEGKEAKETSEDIGLLHEVVSLCHMTSDFQAKAWNISDKNTNGNQTRS SEQ ID
NO: 67 2256 bp NOV11e,
AGATCTGATCCTGTGGTATTGTGGAAATTCCCAGAGGACTTTGGAGACCAGGAAATAC
219903690
TACAGAGTGTGCCAAAGTTCTGTTTTCCCTTTGACGTTGAAAGGGTGTCTCAGAATCA DNA
AGTTGGACAGCACTTTACCTTTGTACTGACAGACATTGAAAGTAAACAGAGATTTGGA Sequence
TTCTGCAGACTGACGTCAGGAGGCACAATTTGTTTATGCATCCTTAGTTACCTTCCCT
GGTTTGAAGTGTATTACAAGCTTCTAAATACTCTTGCAGATTACTTGGCTAAGGAACT
GGAAAATGATTTGAATGAAACTCTCAGATCACTGTATAACCACCCAGTACCAAAGGCA
AATACTCCTGTAAATTTGAGTGTGAACCAAGAGATATTTATTGCCTGTGAGCAAGTTC
TGAAAGATCAGCCTGCTCTAGTACCGCATTCCTACTTCATTGCCCCTGATGTAACTGG
ACTCCCAACAATACCCGAGAGTAGAAATCTTACAGAATATTTTGTTGCCGTGGATGTG
AACAACATGCTGCAGCTGTATGCCAGTATGCTGCATGAAAGGCGCATCGTGATTATCT
CGAGCAAATTAAGCACTTTAACTGCCTGTATCCATGGATCAGCTGCTCTTCTATACCC
AATGTATTGGCAACACATATACATCCCAGTGCTTCCTCCACACCTGCTGGACTACTGC
TGTGCCCCAATGCCATACCTGATTGGAATACACTCCAGCCTCATAGAGAGAGTGAAAA
ACAAATCATTGGAAGATGTTGTTATGTTAAATGTTGATACAAACACATTAGAATCACC
ATTTAGTGACTTGAACAACCTACCAAGTGATGTGGTCTCGGCCTTGAAAAATAAACTG
AAGAAGCAGTCTACAGCTACGGGTGATGGAGTAGCTAGGGCCTTTCTTAGAGCACAGG
CTGCTTTGTTTGGATCCTACAGAGATGCACTGAGATACAAACCTGGTGAGCCCATCAC
TTTCTGTGAGGAGAGTTTTGTAAAGCACCGCTCAAGCGTGATGAAACAGTTCCTGGAA
ACTGCCATTAACCTCCAGCTTTTTAAGCAGTTTATCGATGGTCGACTGGCAAAACTAA
ATGCAGGAAGGGGTTTCTCTGATGTATTTGAAGAAGAGATCACTTCAGGTGGCTTTTG
TGGAGGGAACCCGAGGTCATATCAACAATGGGTGCATACAGTCAAGAAAGGAGGTGCA
CTGTTCAACACAGCAATGACCAAAGCAACCCCTGCTGTACGGACAGCATATAAATTTG
CAAAAAATCATGCAAAGCTGGGACTAAAGGAAGTGAAGAGTAAACTAAAACACAAGGA
AAATGAAGAAGATTATGGGACCTGTTCTAGTTCTGTACAATATACACCAGTTTACAAA
TTACACAATGAAAAGGGAGGAAACTCAGAAAAGCGTAAGCTTGCTCAGGCACGCTTAA
AAAGGCCTCTTAAGAGCCTTGATGGTGCTCTATATGATGATGAAGATGATGATGACAT
TGAAAGAGCAAGCAAGTTATCTTCTGAAGATGGTGAAGAAGCTTCTGCTTATCTCTAT
GAGAGTGATGACTCTGTTGAAACAAGAGTGAAGACTCCTTACTCAGGTGAAATGGACT
TACTAGGAGAGATTCTTGATACATTGAGCACACACAGCTCAGATCAGGGGAAGCTGGC
AGCTGCAAAGAGCTTGGATTTCTTTAGATCAATGGATGACATTGATTACAAACCTACG
AATAAATCTAATGCTCCTAGTGAGAATAACCTGGCTTTCCTCTGTGGTGGTTCTGGTG
ACCAAGCAGAGTGGAATCTTGGGCAAGACGATAGTGCCCTCCATGGCAAACACCTCCC
TCCATCTCCTAGGAAGCGGGTTTCCTCTAGTGGTTTGACAGATTCTCTGTTTATCCTG
AAAGAGGAAAACAGTAACAAGCACCTCGGTGCTGACAATGTGAGTGACCCTACTTCAG
GACTGGATTTCCAACTCACTTCCCCTGAAGTTTCCCAGACTGATAAAGGAAAAACAGA
AAAGAGGGAAACACTAAGCCAGATTTCAGATGATCTGCTTATACCCGGTCTTGGGCGG
CATTCATCGACTTTTGTTCCTTGGGAGAAAGAAGGGAAAGAAGCCAAAGAGACTTCAG
AAGATATTGGACTGCTCCATGAAGTAGTGTCATTATGTCATATGACATCTGACTTCCA
ACAAAGCTTGAACATTTCAGACAAAAACACAAATGGAAACCAAACTAGATCT ORF Start: at
1 ORF Stop: end of sequence SEQ ID NO: 68 752 aa MW at 83933.6kD
NOV11e, RSDPVVLWKFPEDFGDQEILQSVPKFCFPFDVERVSQNQVGQHFTFVLTDIESKQRFG
219903690
FCRLTSGGTICLCILSYLPWFEVYYKLLNTLADYLAKELENDLNETLRSLYNHPVFKA Protein
NTPVNLSVNQEIFIACEQVLKDQPALVPHSYFIAPDVTGLFTIPESRNLTEYFVAVDV Sequence
NNMLQLYASMLHERRIVIISSKLSTLTACIHGSAALLYFMYWQHIYIPVLPPHLLDYC
CAPMPYLIGIHSSLIERVKNKSLEDVVMLNVDTNTLESPFSDLNNLPSDVVSALKNKL
KKQSTATGDGVARAFLRAQAALFGSYRDALRYKPGEPITFCEESFVKHRSSVMKQFLE
TAINLQLFKQFIDGRLAKLNAGRGFSDVFEEEITSGGFCGGNPRSYQQWVHTVKKGGA
LFNTAMTKATPAVRTAYKFAKNHAKLGLKEVKSKLKHKENEEDYGTCSSSVQYTPVYK
LHNEKGGNSEKRKLAQARLKRPLKSLDGALYDDEDDDDIERASKLSSEDGEEASAYLY
ESDDSVETRVKTPYSGEMDLLGEILDTLSTHSSDQGKLAAAKSLDFFRSMDDIDYKPT
NKSNAPSENNLAFLCGGSGDQAEWNLGQDDSALHGKHLPPSPRKRVSSSGLTDSLFIL
KEENSNKHLGADNVSDPTSGLDFQLTSPEVSQTDKGKTEKRETLSQISDDLLIPGLGR
HSSTFVPWEKEGKEAKETSEDIGLLHEVVSLCHMTSDFQQSLNISDKNTNGNQTRS
[0375] Sequence comparison of the above protein sequences yields
the following sequence relationships shown in Table 11B.
TABLE-US-00058 TABLE 11B Comparison of NOV11a against NOV11b
through NOV11e. Identities/ NOV11a Residues/ Similarities for
Protein Sequence Match Residues the Matched Region NOV11b 29 . . .
731 662/752 (88%) 2 . . . 750 671/752 (89%) NOV11c 29 . . . 731
662/752 (88%) 2 . . . 750 671/752 (89%) NOV11d 29 . . . 731 658/753
(87%) 2 . . . 751 668/753 (88%) NOV11e 29 . . . 731 663/752 (88%) 2
. . . 750 671/752 (89%)
[0376] Further analysis of the NOV11a protein yielded the following
properties shown in Table 11C. TABLE-US-00059 TABLE 11C Protein
Sequence Properties NOV11a PSort 0.3700 probability located in
outside; 0.1900 probability analysis: located in lysosome (lumen);
0.1304 probability located in microbody (peroxisome); 0.1000
probability located in endoplasmic reticulum (membrane) SignalP
Cleavage site between residues 30 and 31 analysis:
[0377] A search of the NOV11a protein against the Geneseq database,
a proprietary database that contains sequences published in patents
and patent publication, yielded several homologous proteins shown
in Table 11D. TABLE-US-00060 TABLE 11D Geneseq Results for NOV11a
NOV11a Identities/ Residues/ Similarities for Geneseq
Protein/Organism/Length Match the Matched Expect Identifier [Patent
#, Date] Residues Region Value AAU82007 Human secreted protein
SECP33 - 8 . . . 430 289/454 (63%) e-163 Homo sapiens, 559 aa. 8 .
. . 457 351/454 (76%) [WO200198353-A2, 27-DEC-2001] AAM39715 Human
polypeptide SEQ ID NO 2860 - 8 . . . 430 289/454 (63%) e-163 Homo
sapiens, 559 aa. 8 . . . 457 351/454 (76%) [WO200153312-A1,
26-JUL-2001] AAM41501 Human polypeptide SEQ ID NO 6432 - 8 . . .
406 275/430 (63%) e-154 Homo sapiens, 545 aa. 13 . . . 438 330/430
(75%) [WO200153312-A1, 26-JUL-2001] ABG03235 Novel human diagnostic
protein #3226 - 188 . . . 378 137/192 (71%) 4e-75 Homo sapiens, 196
aa. 1 . . . 190 164/192 (85%) [WO200175067-A2, 11-OCT-2001]
ABG03235 Novel human diagnostic protein #3226 - 188 . . . 378
137/192 (71%) 4e-75 Homo sapiens, 196 aa. 1 . . . 190 164/192 (85%)
[WO200175067-A2, 11-OCT-2001]
[0378] In a BLAST search of public sequence datbases, the NOV11a
protein was found to have homology to the proteins shown in the
BLASTP data in Table 11E. TABLE-US-00061 TABLE 11E Public BLASTP
Results for NOV11a NOV11a Identities/ Protein Residues/
Similarities for Accession Match the Matched Expect Number
Protein/Organism/Length Residues Portion Value Q9NXU2 CDNA FLJ20054
FIS, CLONE 393 . . . 731 339/339 (100%) 0.0 COL00849 - Homo sapiens
1 . . . 339 339/339 (100%) (Human), 339 aa. AAH22561 HYPOTHETICAL
45.0 KDA 27 . . . 376 340/379 (89%) 0.0 PROTEIN - Homo sapiens 15 .
. . 392 344/379 (90%) (Human), 396 aa. Q9D5B9 4930571B16RIK PROTEIN
- 337 . . . 731 298/407 (73%) e-167 Mus musculus (Mouse), 499 aa.
96 . . . 499 337/407 (82%) AAH27786 SIMILAR TO KIAA1608 8 . . . 623
342/680 (50%) e-166 PROTEIN - Mus musculus 8 . . . 676 439/680
(64%) (Mouse), 1016 aa. Q9H796 CDNA: FLJ21129 FIS, CLONE 8 . . .
426 288/450 (64%) e-162 CAS06266 - Homo sapiens 8 . . . 453 349/450
(77%) (Human), 559 aa.
[0379] PFam analysis predicts that the NOV11a protein contains the
domains shown in the Table 11F. TABLE-US-00062 TABLE 11F Domain
Analysis of NOV11a Identities/ Similarities for Pfam NOV11a the
Matched Expect Domain Match Region Region Value DENN 129 . . . 244
48/120 (40%) 6.4e-35 84/120 (70%)
Example 12
[0380] The NOV12 clone was analyzed, and the nucleotide and encoded
polypeptide sequences are shown in Table 12A. TABLE-US-00063 TABLE
12A NOV12 Sequence Analysis SEQ ID NO: 69 1357 bp NOV12a,
ATGAAACTAATTACCATCCTTTTCCTCTGCTCCAGGCTACTACTAAGTTTAACCCAGG
CG104903-01
AATCACAGTCCGAGGAAATTGATGACTGCAATGACAAGGATTTATTTAAAGCTGTGGA DNA
TGCTGCTCTGAAGAAATATAACAGTCAAAACCAAAGTAACAACCAGTTTGTATTGTAC Sequence
CGCAAAACCTGGCAGGACTGTGAGTACAAGGATGCTGCAAAAGCAGCCACTGGAGAAT
GCACAGCAACCGTGGGGAAGAGGAGCAGTACGAAATTCTCCGTGGCTACCCAGACCTG
CCAGATTACTCCAGCCGAGGGCCCTGTGGTGACAGCCCAGTACGACTGCCTCGGCTGT
GTGCATCCTATATCAACGCAGAGCCCAGACCTGGAGCCCATTCTGAGACACGGCATTC
AGTACTTTAACAACAACACTCAACATTCCTCCCTCTTCACGCTTAATGAAGTAAAACG
GGCCCAAAGACAGGTGGTGGCTGGATTGAACTTTCGAATTACCTACTCAATTGTGCAA
ACGAATTGTTCCAAAGAGAATTTTCTGTTCTTAACTCCAGACTGCAAGTCCCTTTGGA
ATGGTGATACCGGTGAATGTACAGATAATGCATACATCGATATTCAGCTACGAATTGC
TTCCTTCTCACAGAACTGTGACATTTATCCAGGGAAGGATTTTGTACAACCACCTACC
AAGATTTGCGTGGGCTGCCCCAGAGATATACCCACCAACAGCCCAGAGCTGGAGGAGA
CACTGACTCACACCATCACAAAGCTTAATGCAGAGAATAACGCAACTTTCTATTTCAA
GATTGACAATGTGAAAAAAGCAAGAGTACAGGTGGTGGCTGGCAAGAAATATTTTATT
GACTTCGTGGCCAGGGAAACCACATGTTCCAAGGAAAGTAATGAAGAGTTGACCGAAA
GCTGTGAGACCAAAAAACTTGGCCAAAGCCTAGATTGCAACGCTGAAGTTTATGTGGT
ACCCTGGGAGAAAAAAATTTACCCTACTGTCAACTGTCAACCACTGGGAATGATCTCA
CTGATGAAAAGGCCTCCAGGTTTTTCACCTTTCCGATCATCACGAATAGGGGAAATAA
AAGAAGAAACAACTAGTCACCTAAGGTCCTGCGAGTACAAGGGTCGACCCCCAAAGGC
AGGGGCAGAGCCAGCATCTGAGAGGGAGGTCTCTTGACCAATGGGCAGAATCTTCACT
CCAGGCACATAGCCCCAACCACCTCTGCCAGCAACCTTGAGAGGAAGGACAAGAAGAA
AGATGGGATAGAATTTAAATAGAGAAGAATGCCATTTTATCACTCTGCCTCTGGGTGA
AATAAAGATCAGTCTTGATGTTC ORF Start: ATG at 1 ORF Stop: TGA at 1195
SEQ ID NO: 70 398 aa MW at 44684.1kD NOV12a,
MKLITILFLCSRLLLSLTQESQSEEIDDCNDKDLFKAVDAALKKYNSQNQSNNQFVLY
CG104903-01
RKTWQDCEYKDAAKAATGECTATVGKRSSTKFSVATQTCQITPAEGPVVTAQYDCLGC Protein
VHPISTQSPDLEPILRHGIQYFNNNTQHSSLFTLNEVKRAQRQVVAGLNFRITYSIVQ Sequence
TNCSKENFLFLTPDCKSLWNGDTGECTDNAYIDIQLRIASFSQNCDIYPGKDFVQPPT
KICVGCPRDIPTNSPELEETLTHTITKLNAENNATFYFKIDNVKKARVQVVAGKKYFI
DFVARETTCSKESNEELTESCETKKLGQSLDCNAEVYVVPWEKKIYPTVNCQPLGMIS
LMKRPPGFSPFRSSRIGEIKEETTSHLRSCEYKGRPPKAGAEPASEREVS SEQ ID NO: 71
1848bp NOV12b,
ATGAAACTAATTACCATCCTTTTCCTCTGCTCCAGGCTACTACTAAGTTTAACCCAGG
CG104903-02
AATCACAGTCCGAGGAAATTGATGACTGCAATGACAAGGATTTATTTAAAGCTGTGGA DNA
TGCTGCTCTGAAGAAATATAACAGTCAPAACCAAAGTAACAACCAGTTTGTATTGTAC Sequence
CGCAAAACCTGGCAGGACTGTGAGTACAAGGATGCTGCAAAAGCAGCCACTGGAGAAT
GCACAGCAACCGTGGGGAAGAGGAGCAGTACGAAATTCTCCGTGGCTACCCAGACCTG
CCAGATTACTCCAGCCGAGGGCCCTGTGGTGACAGCCCAGTACGACTGCCTCGGCTGT
GTGCATCCTATATCAACGCAGAGCCCAGACCTGGAGCCCATTCTGAGACACGGCATTC
AGTACTTTAACAACAACACTCAACATTCCTCCCTCTTCACGCTTAATGAAGTAAAACG
GGCCCAAAGACAGGTGGTGGCTGGATTGAACTTTCGAATTACCTACTCAATTGTGCAA
ACGAATTGTTCCAAAGAGAATTTTCTGTTCTTAACTCCAGACTGCAAGTCCCTTTGGA
ATGGTGATACCGGTGAATGTACAGATAATGCATACATCGATATTCAGCTACGAATTGC
TTCCTTCTCACAGAACTGTGACATTTATCCAGGGAAGGATTTTGTACAACCACCTACC
AAGATTTGCGTGGGCTGCCCCAGAGATATACCCACCAACAGCCCAGAGCTGGAGGAGA
CACTGACTCACACCATCACAAAGCTTAATGCAGAGAATAACGCAACTTTCTATTTCAA
GATTGACAATGTGAAAAAAGCAAGAGTACAGGTGGTGGCTGGCAAGAAATATTTTATT
GACTTCGTGGCCAGGGAAACCACATGTTCCAAGGAAAGTAATGAAGAGTTGACCGAAA
GCTGTGAGACCAAAAAACTTGGCCAAAGCCTAGATTGCAACGCTGAAGTTTATGTGGT
ACCCTGGGAGAAAAAAATTTACCCTACTGTCAACTGTCAACCACTGGGAATGATCTCA
CTGATGAAAAGGCCTCCAGGTTTTTCACCTTTCCGATCATCACGAATAGGGGAAATAA
AAGAAGAAACAACTGTAAGTCCACCCCACACTTCCATGGCACCTGCACAAGATGAAGA
GCGGGATTCAGGAAAAGAACAAGGGCATACTCGTAGACATGACTGGGGCCATGAAAAA
CAAAGAAAACATAATCTTGGCCATGGCCATAAACATGAACGTGACCAAGGGCATGGGC
ACCAAAGAGGACATGGCCTTGGCCATGGACACGAACAACAGCATGGTCTTGGTCATGG
ACATAAGTTCAAACTTGATGATGATCTTGAACACCAAGGGGGCCATGTCCTTGACCAT
GGACATAAGCATAAGCATGGTCATGGCCACGGAAAACATAAAAATAAAGGCAAAAAGA
ATGGAAAGCACAATGGTTGGAAAACAGAGCATTTGGCAAGCTCTTCTGAAGACAGTAC
TACACCTTCTGCACAGACACAAGAGAAGACAGAAGGGCCAACACCCATCCCTTCCCTA
GCCAAGCCAGGTGTAACAGTTACCTTTTCTGACTTTCAGGACTCTGATCTCATTGCAA
CTATGATGCCTCCTATATCACCAGCTCCCATACAGAGTGATGACGATTGGATCCCTGA
TATCCAGACAGACCCAAATGGCCTTTCATTTAACCCAATATCAGATTTTCCAGACACG
ACCTCCCCAAAATGTCCTGGACGCCCCTGGAAGTCAGTTAGTGAAATTAATCCAACCA
CACAAATGAAAGAATCTTATTATTTCGATCTCACTGATGGCCTTTCTTAA ORF Start: ATG
at 1 ORF Stop: TAA at 1846 SEQ ID NO: 72 615 aa MW at 68746.1kD
NOV12b, MKLITILFLCSRLLLSLTQESQSEEIDDCNDKDLFKAVDAALKKYNSQNQSNNQFVLY
CG104903-02
RKTWQDCEYKDAAKAATGECTATVGKRSSTKFSVATQTCQITPAEGPVVTAQYDCLGC Protein
VHPISTQSPDLEPILRHGIQYFNNNTQHSSLFTLNEVKRAQRQVVAGLNFRITYSIVQ Sequence
TNCSKENFLFLTPDCKSLWNGDTGECTDNAYIDIQLRIASFSQNCDIYPGKDFVQPFT
KICVGCPRDIPTNSFELEETLTHTITKLNAENNATFYFKIDNVKKARVQVVAGKKYFI
DFVARETTCSKESNEELTESCETKKLGQSLDCNAEVYVVPWEKKIYPTVNCQPLGMIS
LMKRPPGFSPFRSSRIGEIKEETTVSPPHTSMAPAQDEERDSGKEQGHTRRHDWGHEK
QRKHNLGHGHKHERDQGHGHQRGHGLGHGHEQQBGLGHGHKFKLDDDLEHQGGHVLDH
GHKHKHGHGHGKHKNKGKKNGKHNGWKTEHLASSSEDSTTPSAQTQEKTEGPTPIPSL
AKPGVTVTFSDFQDSDLIATMMPFISPAPIQSDDDWIPDIQTDPNGLSFNPISDFPDT
TSPKCPGRPWKSVSEINPTTQMKESYYFDLTDGLS SEQ ID NO: 73 1981 bp NOV12c,
AATTCCGGTTGAAACCATCCCTCAGCTCCTAGAGGGAGATTGTTAGATCATGAAACTA
CG104903-03
ATTACCATCCTTTTCCTCTGCTCCAGGCTACTACTAAGTTTAACCCAGGAATCACAGT DNA
CCGAGGAAATTGACTGCAATGACAAGGATTTATTTAAAGCTGTGGATGCTGCTCTGAA Sequence
GAAATATAACAGTCAAAACCAAAGTAACAACCAGTTTGTATTGTACCGCATAACTGAA
GCCACTAAGACGGTTGGCTCTGACACGTTTTATTCCTTCAAGTACGAAATCAAGGAGG
GGGATTGTCCTGTTCAAAGTGGCAAAACCTGGCAGGACTGTGAGTACAAGGATGCTGC
AAAAGCAGCCACTGGAGAATGCACGGCAACCGTGGGGAAGAGGAGCAGTACGAAATTC
TCCGTGGCTACCCAGACCTGCCAGATTACTCCAGCCGAGGGCCCTGTGGTGACAGCCC
AGTACGACTGCCTCGGCTGTGTGCATCCTATATCAACGCAGAGCCCAGACCTGGAGCC
CATTCTGAGACACGGCATTCAGTACTTTAACAACAACACTCAACATTCCTCCCTCTTC
ATGCTTAATGAAGTAAAACGGGCCCAAAGACAGGTGGTGGCTGGATTGAACTTTCGAA
TTACCTACTCAATTGTGCAAACGAATTGTTCCAAAGAGAATTTTCTGTTCTTAACTCC
AGACTGCAAGTCCCTTTGGAATGGTGATACCGGTGAATGTACAGATAATGCATACATC
GATATTCAGCTACGAATTGCTTCCTTCTCACAGAACTGTGACATTTATCCAGGGAAGG
ATTTTGTACAACCACCTACCAAGATTTGCGTGGGCTGCCCCAGAGATATACCCACCAA
CAGCCCAGAGCTGGAGGAGACACTGACTCACACCATCACAAAGCTTAATGCAGAGAAT
AACGCAACTTTCTATTTCAAGATTGACAATGTGAAAAAAGCAAGAGTACAGGTGGTGG
CTGGCAAGAAATATTTTATTGACTTCGTGGCCAGGGAAACCACATGTTCCAAGGAAAG
TAATGAAGAGTTGACCGAAAGCTGTGAGACCAAAAAAGTTGGCCAAAGCCTAGATTGC
AACGCTGAAGTTTATGTGGTACCCTGGGAGAAAAAAATTTACCCTACTGTCAACTGTC
AACCACTGGGAATGATCTCACTGATGAAAAGGCCTCCAGGTTTTTCACCTTTCCGATC
ATCACGAATAGGGGAAATAAAAGAAGAAACAACTGTAAGTCCACCCCACACTTCCATG
GCACCTGCACAAGATGAAGAGCGGGATTCAGGAAAAGAACAAGGGCATACTCGTAGAC
ATGACTGGGGCCATGAAAAACAAAGAAAACATAATCTTGGCCATGGCCATAAACATGA
ACGTGACCAAGGGCATGGGCACCAAAGAGGACATGGCCTTGGCCATGGACACGAACAA
CAGCATGGTCTTGGTCATGGACATAAGTTCAAACTTGATGATGATCTTGAACACCAAG
GGGGCCATGTCCTTGACCATGGACATAAGCATAAGCATGGTCATGGCCACGGAAAACA
TAAAAATAAAGGCAAAAAGAATGGAAAGCACAATGGTTGGAAAACAGAGCATTTGGCA
AGCTCTTCTGAAGACAGTACTACACCTTCTGCACAGACACAAGAGAAGACAGAAGGGC
CAACACCCATCCCTTCCCTAGCCAAGCCAGGTGTAACAGTTACCTTTTCTGACTTTCA
GGACTCTGATCTCATTGCAACTATGATGCCTCCTATATCAGCAGCTCCCATACAGAGT
GATGACGATTGGATCCCTGATATCCAGATAGACCCAAATGGCCTTTCATTTAACCCAA
TATCAGATTTTCCAGACACGACCTCCCCAAAATGTCCTGGACGCCCCTGGAAGTCAGT
TAGTGAAATTAATCCAACCACACAAATGAAAGAATCTTATTATTTCGATCTCACTGAT
GGCCTTTCT ORF Start: ATG at 50 ORF Stop: end of sequence SEQ ID NO:
74 644 aa MW at 71956.8kD NOV12c,
MKLITILFLCSRLLLSLTQESQSEEIDCNDKDLFKAVDAALKKYNSQNQSNNQFVLYR
GG104903-03
ITEATKTVGSDTFYSFKYEIKEGDCPVQSGKTWQDCEYKDAAKAATGECTATVGKRSS Protein
TKFSVATQTCQITPAEGPVVTAQYDCLGCVHPISTQSPDLEPILRHGIQYFNNNTQHS Sequence
SLFMLNEVKRAQRQVVAGLNFRITYSIVQTNCSKENFLFLTPDCKSLWNGDTGECTDN
AYIDIQLRIASFSQNCDIYPGKDFVQPPTKICVGCPRDIPTNSPELEETLTHTITKLN
AENNATFYFKIDNVKKARVQVVAGKKYFIDFVARETTCSKESNEELTESCETKKLGQS
LDCNAEVYVVPWEKKIYPTVNCQPLGMTSLMKRPPGFSPFRSSRIGEIKEETTVSPPH
TSMAPAQDEERDSGKEQGHTRRHDWGHEKQRKHNLGHGHKHERDQGHGHQRGHGLGHG
HEQQHGLGHGHKFKLDDDLEHQGGHVLDHGHKHKBGHGHGKHKNKGKKNGKHNGWKTE
HLASSSEDSTTPSAQTQEKTEGPTPIPSLAKPGVTVTFSDFQDSDLIATMMPPISPAP
IQSDDDWIPDIQIDPNGLSFNPISDFPDTTSPKCPGRPWKSVSEINPTTQMKESYYFD LTDGLS
SEQ ID NO: 75 1297 bp NOV12d,
AATTCCGGTTGAAACCATCCCTCAGCTCCTAGAGGGAGATTGTTAGATCATGAAACTA
CG104903-05
ATTACCATCCTTTTCCTCTGCTCCAGGCTACTACTAAGTTTAACCCAGGAATCACAGT DNA
CCGAGGAAATTGACTGCAATGACAAGGATTTATTTAAAGCTGTGGATGCTGCTCTGAA Sequence
GAAATATAACAGTCAAAACCAAAGTAACAACCAGTTTGTATTGTACCGCATAACTGAA
GCCACTAAGACGGTTGGCTCTGACACGTTTTATTCCTTCAAGTACGAAATCAAGGAGG
GGGATTGTCCTGTTCAAAGTGGCAAAACCTGGCAGGACTGTGAGTACAAGGATGCTGC
AAAAGCAGCCACTGGAGAATGCACAGCAACCGTGGGGAAGAGGAGCAGTACGAAATTC
TCCGTGGCTACCCAGACCTGCCAGATTACTCCAGCCGAGGGCCCTGTGGTGACAGCCC
AGTACGACTGCCTCGGCTGTGTGCATCCTATATCAACGCAGAGCCCAGGTTTTTCACC
TTTCCGATCATCACGAATAGGGGAAATAAAAGAAGAAACAACTGTAAGTCCACCCCAC
ACTTCCATGGCACCTGCACAAGATGAAGAGCGGGATTCAGGAAAAGAACAAGGGCATA
CTCGTAGACATGACTGGGGCCATGAAAAACAAAGAAAACATAATCTTGGCCATGGCCA
TAAACATGAACGTGACCAAGGGCATGGGCACCAAAGAGGACATGGCCTTGGCCATGGA
CACGAACAACAGCATGGTCTTGGTCATGGACATAAGTTCAAACTTGATGATGATCTTG
AACACCAAGGGGGCCATGTCCTTGACCATGGACATAAGCATAAGCATGGTCATGGCCA
CGGAAAACATAAAAATAAAGGCAAAAAGAATGGAAAGCACAATGGTTGGAAAACAGAG
CATTTGGCAAGCTCTTCTGAAGACAGTACTACACCTTCTGCACAGACACAAGAGAAGA
CAGAAGGGCCAACACCCATCCCTTCCCTAGCCAAGCCAGGTGTAACAGTTACCTTTTC
TGACTTTCAGGACTCTGATCTCATTGCAACTATGATGCCTCCTATATCACCAGCTCCC
ATACAGAGTGATGACGATTGGATCCCTGATATCCAGATAGACCCAAATGGCCTTTCAT
TTAACCCAATATCAGATTTTCCAGACACGACCTCCCCAAAATGTCCTGGACGCCCCTG
GAAGTCAGTTAGTGAAATTAATCCAACCACACAAATGAAAGAATCTTATTATTTCGAT
CTCACTGATGGCCTTTCTTAA ORF Start: ATG at 50 ORF Stop: TAA at 1295
SEQ ID NO: 76 415 aa MW at 45897.3kD NOV12d,
MKLITILFLCSRLLLSLTQESQSEEIDCNDKDLFKAVDAALKKYNSQNQSNNQFVLYR
CG104903-05
ITEATKTVGSDTFYSFKYEIKEGDCPVQSGKTWQDCEYKDAAKAATGECTATVGKRSS Protein
TKFSVATQTCQITPAEGPVVTAQYDCLGCVHPISTQSPGFSPFRSSRIGEIKEETTVS Sequence
PPHTSMAPAQDEERDSGKEQGHTRRHDWGHEKQRKHNLGHGHKHERDQGHGHQRGHGL
GHGHEQQHGLGHGHKFKLDDDLEHQGGHVLDHGHKHKHGHGHGKHKNKGKKNGKHNGW
KTEHLASSSEDSTTPSAQTQEKTEGPTPIPSLAKPGVTVTFSDFQDSDLIATMMPFIS
PAPIQSDDDWIPDIQIDPNGLSFNPISDFPDTTSPKCPGRPWKSVSEINPTTQMKESY
YFDLTDGLS SEQ ID NO: 77 1892 bp NOV12e,
AATTCCGGTTGAAACCATCCCTCAGCTCCTAGAGGGAGATTGTTAGATCATGAAACTA
CG104903-06
ATTACCATCCTTTTCCTCTGCTCCAGGCTACTACTAAGTTTAACCCAGGAATCACAGT DNA
CCGAGGAAATTGACTGCAATGACAAGGATTTATTTAAAGCTGTGGATGCTGCTCTGAA Sequence
GAAATATAACAGTCAAAACCAAAGTAACAACCAGTTTGTATTGTACCGCATAACTGAA
GCCACTAAGACGGTTGGCTCTGACACGTTTTATTCCTTCAAGTACGAAATCAAGGAGG
GGGATTGTCCTGTTCAAAGTGGCAAAACCTGGCAGGACTGTGAGTACAAGGATGCTGC
AAAAGCAGCCACTGGAGAATGCACAGCAACCGTGGGAAGAGGAGCAGTACGAAATTCT
CCGTGGCTACCCAGACCTGGAGCCCATTCTGAGACACGGCATTCAGTACTTTAACAAC
AACACTCAACATTCCTCCCTCTTCACGCTTAATGAAGTAAAACGGGCCCAAAGACAGG
TGGTGGCTGGATTGAACTTTCGAATTACCTACTCAATTGTGCAAACGAATTGTTCCAA
AGAGAATTTTCTGTTCTTAACTCCAGACTGCAAGTCCCTTTGGAATGGTGATACCGGT
GAATGTACAGATAATGCATACATCGATATTCAGCTACGAATTGCTTGCTTCTCACAGA
ACTGTGACATTTATCCAGGGAAGGATTTTGTACAACCACCTACCAAGATTTGCGTGGG
CTGCCCCAGAGATATACCCACCAACAGCCCAGAGCTGGAGGAGACACTGACTCACACC
ATCACAAAGCTTAATGCAGAGAATAACGCAACTTTCTATTTCAAGATTGACAATGTGA
AAAAAGCAAGAGTACAGGTGGTGGCTGGCAAGAAATATTTTATTGACTTCGTGGCCAG
GGAAACCACATGTTCCAAGGAAAGTAATGAAGAGTTGACCGAAAGCTGTGAGACCAAA
AAACTTGGCCAAAGCCTAGATTGCAACGCTGAAGTTTATGTGGTACCCTGGGAGAAAA
AAATTTACCCTACTGTCAACTGTCAACCACTGGGAATGATCTCACTGATGAAAAGGCC
TCCAGGTTTTTCACCTTTCCGATCATCACGAATAGGGGAAATAAAAGAAGAAACAACT
GTAAGTCCACCCCACACTTCCATGGCACCTGCACAAGATGAAGAGCGGGATTCAGGAA
AAGAACAAGGGCATACTCGTAGACATGACTGGGGCCATGAAAAACAAAGAAAACATAA
TCTTGGCCATGGCCATAAACATGAACGTGACCAAGGGCATGGGCACCAAAGAGGACAT
GGCCTTGGCCATGGACACGAACAACAGCATGGTCTTGGTCATGGACATAAGTTCAAAC
TTGATGATGATCTTGAACACCAAGGGGGCCATGTCCTTGACCATGGACATAAGCATAA
GCATGGTCATGGCCACGGAAAACATAAAAATAAAGGCAAAAAGAATGGAAAGCACAAT
GGTTGGAAAACAGAGCATTTGGCAAGCTCTTCTGAAGACAGTACTACACCTTCTGCAC
AGACACAAGAGAAGACAGAAGGGCCAACACCCATCCCTTCCCTAGCCAAGCCAGGTGT
AACAGTTACCTTTTCTGACTTTCAGGACTCTGATCTCATTGCAACTATGATGCCTCCT
ATATCACCAGCTCCCATACAGAGTGATGACGATTGGATCCCTGATATCCAGATAGACC
CAAATGGCCTTTCATTTAACCCAATATCAGATTTTCCAGACACGACCTCCCCAAAATG
TCCTGGACGCCCCTGGAAGTCAGTTAGTGAAATTAATCCAACCACACAAATGAAAGAA
TCTTATTATTTCGATCTCACTGATGGCCTTTCTTAA ORF Start: ATG at 50 ORF Stop:
TAA at 458 SEQ ID NO: 78 136 aa MW at 15218.9kD NOV12e,
MKLITILFLCSRLLLSLTQESQSEEIDCNDKDLFKAVDAALKKYNSQNQSNNQFVLYR
CG104903-06
ITEATKTVGSDTFYSFKYEIKEGDCPVQSGKTWQDCEYKDAAKAATGECTATVGRGAV Protein
RNSPWLPRPGAHSETRHSVL Sequence SEQ ID NO: 79 670 bp NOV12f,
ATGAAACTAATTACCATCCTTTTCCTCTGCTCCAGGCTACTACTAAGTTTAACCCAGG
CG104903-07
AATCACAGTCCGAGGAAATTGATGACTGCAATGACAAGGATTTATTTAAAGCTGTGGA DNA
TGCTGCTCTGAAGAAATATAACAGTCAAAACCAAAGTAACAACCAGTTTGTATTGTAC Sequence
CGCAAAACCTGGCAGGACTGTGAGTACAAGGATGCTGCAAAAGCAGCCACTGGAGAAT
GCACAGCAACCGTGGGGAAGAGGAGCAGTACGAAATTCTCCGTGGCTACCCAGACCTG
CCAGATTACTCCAGCCGAGGGCCCTGTGGTGACAGCCCAGTACGACTGCCTCGGCTGT
GTGCATCCTATATCAACGCAGAGCCCAGGTTTTTCACCTTTCCGATCATCACGAATAG
GGGAAATAAAAGAAGAAACAACTAGTCACCTAAGGTCCTGCGAGTACAAGGGTCGACC
CCCAAAGGCAGGGGCAGAGCCAGCATCTGAGAGGGAGGTCTCTTGACCAATGGGCAGA
ATCTTCACTCCAGGCACATAGCCCCAACCACCTCTGCCAGCAACCTTGAGAGGAAGGA
CAAGAAGAAAGATGGGATAGAATTTAAATAGAGAAGAATGCCATTTTATCACTCTGCC
TCTGGGTGAAATAAAGATCAGTCTTGATGTTC ORF Start: ATG at 1 ORF Stop: TGA
at 508 SEQ ID NO: 80 169 aa MW at 18654.7kD NOV12f,
IMKLITILFLCSRLLLSLTQESQSEEIDDCNKDLFKAVDAALKKYNSQNQSNNQFVLY
CG104903-07
RKTWQDCEYKDAAKAATGECTATVGKRSSTKFSVATQTCQITPAEGPVVTAQYDCLGC Protein
VHPISTQSPGFSPFRSSRIGEIKEETTSHLRSCEYKGRPPKAGAEPASEREVS Sequence SEQ
ID NO: 81 1193 bp NOV12g,
ATGAAACTAATTACCATCCTTTTCCTCTGCTCCAGGCTACTACTAAGTTTAACCCAGG
CG104903-08
AATCACAGTCCGAGGAAATTGACTGCAATGACAAGGATTTATTTAAAGCTGTGGATGC DNA
TGCTCTGAAGAAATATAACAGTCAAAACCAAAGTAACAACCAGTTTGTATTGTACCGC Sequence
ATAACTGAAGCCACTAAGACGGCCACTGGAGAATGCACGGCAACCGTGGGGAAGAGGA
GCAGTACGAAATTCTCCGTGGCTACCCAGACCTGCCAGATTACTCCAGCCGAGGGCCC
TGTGGTGACAGCCCAGTACGACTGCCTCGGCTGTGTGCATCCTATATCAACGCAGAGC
CCAGACCTGGAGCCCATTCTGAGACACGGCATTCAGTACTTTAACAACAACACTCAAC
ATTCCTCCCTCTTCACGCTTAATGAAGTAAAACGGGCCCAAAGACAGGTGGTGGCTGG
ATTGAACTTTCGAATTACCTACTCAATTGTGCAAACGAATTGTTCCAAAGAGAATTTT
CTGTTCTTAACTCCAGACTGCGAGTCCCTTTGGAATGGTGATACCGGTGAATGTACAG
ATAATGCATACATCGATATTCAGCTACGAATTGCTTCCTTCTCACAGAACTGTGACAT
TTATCCAGGGAAGGATTTTGTACAACCACCTACCAAGATTTGCGTGGGCTGCCCCAGA
GATATACCCACCAACAGCCCAGAGCTGGAGGAGACACTGACTCACACCATCACAAAGC
TTAATGCAGAGAATAACGCAACTTTCTATTTCAAGATTGACAATGTGAAAAAAGCAAG
AGTACAGGTGGTGGCTGGCAAGAAATATTTTATTGACTTCGTGGCCAGGGAAACCACA
TGTTCCAAGGAAAGTAATGAAGAGTTGACCGAAAGCTGTGAGACCAAAAAACTTGGCC
AAAGCCTAGATTGCAACGCTGAAGTTTATGTGGTACCCTGGGAGAAAAAAATTTACCC
TACTGTCAACTGTCAACCACTGGGAATGATCTCACTGATGAAAAGGCCTCCAGGTTTT
TCACCTTTCCGATCATCACGAATAGGGGAAATAAAAGAAGAAACAACTAGTCACCTAA
GGTCCTGCGAGTACAAGGGTCGACCCCCAAAGGCAGGGGCAGAGCCAGTATCTGAGAG
GGAGGTCTCTTGACCAATGGGCAGAATCTTCAC ORF Start: ATG at 1 ORF Stop: TGA
at 1171 SEQ ID NO: 82 390 aa MW at 43704.0kD NOV12g,
MKLITILFLCSRLLLSLTQESQSEEIDCNDKDLFKAVDAALKKYNSQNQSNNQFVLYR
CG104903-08
ITEATKTATGECTATVGKRSSTKFSVATQTCQITPAEGPVVTAQYDCLGCVHPISTQS Protein
PDLEPILRHGIQYFNNNTQHSSLFTLNEVKRAQRQVVAGLNFRITYSIVQTNCSKENF Sequence
LFLTPDCESLWNGDTGECTDNAYIDIQLRIASFSQNCDIYPGKDFVQPPTKICVGCPR
DIPTNSPELEETLTHTITKLNAENNATFYFKIDNVKKARVQVVAGKKYFIDFVARETT
CSKESNEELTESCETKKLGQSLDCNAEVYVVPWEKKIYPTVNCQPLGMISLMKRPPGF
SPFRSSRIGEIKEETTSHLRSCEYKGRPPKAGAEPVSEREVS SEQ ID NO: 83 1984 bp
NOV12h, AATTCCGGTTGAAACCATCCCTCAGCTCCTAGAGGGAGATTGTTAGATCATGAAACTA
CG104903-09
ATTACCATCCTTTTCCTCTGCTCCAGGCTACTACTAAGTTTAACCCAGGAATCACAGT DNA
CCGAGGAAATTGACTGCAATGACAAGGATTTATTTAAAGCTGTGGATGCTGCTCTGAA Sequence
GAAATATAACAGTCAAAACCAAAGTAACAACCAGTTTGTATTGTACCGCATAACTGAA
GCCACTAAGACGGTTGGCTCTGACACGTTTTATTCCTTCAAGTACGAAATCAAGGAGG
GGGATTGTCCTGTTCAAAGTGGCAAAACCTGGCAGGACTGTGAGTACAAGGATGCTGC
AAAAGCAGCCACTGGAGAATGCACGGCAACCGTGGGGAAGAGGAGCAGTACGAAATTC
TCCGTGGCTACCCAGACCTGCCAGATTACTCCAGCCGAGGGCCCTGTGGTGACAGCCC
AGTACGACTGCCTCGGCTGTGTGCATCCTATATCAACGCAGAGCCCAGACCTGGAGCC
CATTCTGAGACACGGCATTCAGTACTTTAACAACAACACTCAACATTCCTCCCTCTTC
ATGCTTAATGAAGTAAAACGGGCCCAAAGACAGGTGGTGGCTGGATTGAACTTTCGAA
TTACCTACTCAATTGTGCAAACGAATTGTTCCAAAGAGAATTTTCTGTTCTTAACTCC
AGACTGCAAGTCCCTTTGGAATGGTGATACCGGTGAATGTACAGATAATGCATACATC
GATATTCAGCTACGAATTGCTTCCTTCTCACAGAACTGTGACATTTATCCAGGGAAGG
ATTTTGTACAACCACCTACCAAGATTTGCGTGGGCTGCCCCAGAGATATACCCACCAA
CAGCCCAGAGCTGGAGGAGACACTGACTCACACCATCACAAAGCTTAATGCAGAGAAT
AACGCAACTTTCTATTTCAAGATTGACAATGTGAAAAAAGCAAGAGTACAGGTGGTGG
CTGGCAAGAAATATTTTATTGACTTCGTGGCCAGGGAAACCACATGTTCCAAGGAAAG
TAATGAAGAGTTGACGGAAAGCTGTGAGACCAAAAAACTTGGCCAAAGCCTAGATTGC
AACGCTGAAGTTTATGTGGTACCCTGGGAGAAAAAAATTTACCCTACTGTCAACTGTC
AACCACTGGGAATGATCTCACTGATGAAAAGGCCTCCAGGTTTTTCACCTTTCCGATC
ATCACGAATAGGGGAAATAAAAGAAGAAACAACTGTAAGTCCACCCCACACTTCCATG
GCACCTGCACAAGATGAAGAGCGGGATTCAGGAAAAGAACAAGGGCATACTCGTAGAC
ATGACTGGGGCCATGAAAAACAAAGAAAACATAATCTTGGCCATGGCCATAAACATGA
ACGTGACCAAGGGCATGGGCACCAAAGAGGACATGGCCTTGGCCATGGACACGAACAA
CAGCATGGTCTTGGTCATGGACATAAGTTCAAACTTGATGATGATCTTGAACACCAAG
GGGGCCATGTCCTTGACCATGGACATAAGCATAAGCATGGTCATGGCCACGGAAAACA
TAAAAATAAAGGCAAAAAGAATGGAAAGCACAATGGTTGGAAAACAGAGCATTTGGCA
AGCTCTTCTGAAGACAGTACTACACCTTCTGCACAGACACAAGAGAAGACAGAAGGGC
CAACACCCATCCCTTCCCTAGCCAAGCCAGGTGTAACAGTTACCTTTTCTGACTTTCA
GGACTCTGATCTCATTGCAACTATGATGCCTCCTATATCACCAGCTCCCATACAGAGT
GATGACGATTGGATCCCTGATATCCAGATAGACCCAAATGGCCTTTCATTTAACCCAA
TATCAGATTTTCCAGACACGACCTCCCCAAAATGTCCTGGACGCCCCTGGAAGTCAGT
TAGTGAAATTAATCCAACCACACAAATGAAAGAATCTTATTATTTCGATCTCACTGAT
GGCCTTTCTTAA ORF Start: ATG at 50 ORF Stop: TAA at 1982 SEQ ID NO:
84 644 aa MW at 71956.8kD NOV12h,
MKLITILFLCSRLLLSLTQESQSEEIDCNDKDLFKAVDAALKKYNSQNQSNNQFVLYR
CG104903-09
ITEATKTVGSDTFYSFKYEIKEGDCPVQSGKTWQDCEYKDAAKAATGECTATVGKRSS Protein
TKFSVATQTCQITPAEGPVVTAQYDCLGCVHPISTQSPDLEPILRHGIQYFNNNTQHS Sequence
SLFMLNEVKRAQRQVVAGLNFRITYSIVQTNCSKENFLFLTPDCKSLWNGDTGECTDN
AYIDIQLRIASFSQNCDIYPGKDFVQPPTKICVGCPRDIPTNSPELEETLTHTITKLN
AENNATFYFKIDNVKKARVQVVAGKKYFIDFVARETTCSKESNEELTESCETKKLGQS
LDCNAEVYVVPWEKKIYPTVNCQPLGMISLMKRPPGFSPFRSSRIGEIKEETTVSPPH
TSMAPAQDEERDSGKEQGHTRRHDWGHEKQRKHNLGHGHKHERDQGHGHQRGHGLGHG
HEQQHGLGHGHKFKLDDDLEHQGGHVLDHGHKHKHGHGHGKHKNKGKKNGKHNGWKTE
HLASSSEDSTTPSAQTQEKTEGPTPIPSLAKPGVTVTFSDFQDSDLIATMMPPISPAP
IQSDDDWIPDIQIDPNGLSFNPISDFPDTTSPKCPGRPWKSVSEINPTTQMKESYYFD
LTDGLS
[0381] Sequence comparison of the above protein sequences yields
the following sequence relationships shown in Table 12B.
TABLE-US-00064 TABLE 12B Comparison of NOV12a against NOV12b
through NOV12h. NOV12a Identities/ Protein Residues/Match
Similarities for Sequence Residues the Matched Region NOV12b 26 . .
. 396 343/371 (92%) 26 . . . 387 344/371 (92%) NOV12c 28 . . . 396
340/399 (85%) 27 . . . 416 341/399 (85%) NOV12d 28 . . . 129 90/132
(68%) 27 . . . 158 90/132 (68%) NOV12e 28 . . . 84 47/87 (54%) 27 .
. . 113 48/87 (55%) NOV12f 26 . . . 129 92/104 (88%) 26 . . . 129
92/104 (88%) NOV12g 28 . . . 398 349/371 (94%) 27 . . . 390 351/371
(94%) NOV12h 28 . . . 396 340/399 (85%) 27 . . . 416 341/399
(85%)
[0382] Further analysis of the NOV12a protein yielded the following
properties shown in Table 12C. TABLE-US-00065 TABLE 12C Protein
Sequence Properties NOV12a PSort 0.5135 probability located in
outside; 0.1900 analysis: probability located in lysosome (lumen);
0.1000 probability located in endoplasmic reticulum (membrane);
0.1000 probability located in endoplasmic reticulum (lumen) SignalP
Cleavage site between residues 24 and 25 analysis:
[0383] A search of the NOV12a protein against the Geneseq database,
a proprietary database that contains sequences published in patents
and patent publication, yielded several homologous proteins shown
in Table 12D. TABLE-US-00066 TABLE 12D Geneseq Results for NOV12a
NOV12a Identities/ Geneseq Protein/Organism/Length Residues/Match
Similarities for Expect Identifier [Patent #, Date] Residues the
Matched Region Value ABG21101 Novel human diagnostic protein 1 . .
. 396 375/426 (88%) 0.0 #21092 - Homo sapiens, 644 aa. 1 . . . 416
376/426 (88%) [WO200175067-A2, 11-OCT-2001] ABG21101 Novel human
diagnostic protein 1 . . . 396 375/426 (88%) 0.0 #21092 - Homo
sapiens, 644 aa. 1 . . . 416 376/426 (88%) [WO200175067-A2,
11-OCT-2001] ABG21105 Novel human diagnostic protein 1 . . . 398
377/435 (86%) 0.0 #21096 - Homo sapiens, 435 aa. 2 . . . 435
380/435 (86%) [WO200175067-A2, 11-OCT-2001] ABG21105 Novel human
diagnostic protein 1 . . . 398 377/435 (86%) 0.0 #21096 - Homo
sapiens, 435 aa. 2 . . . 435 380/435 (86%) [WO200175067-A2,
11-OCT-2001] AAP40257 Bradykinin protein precursor: 1 . . . 398
297/428 (69%) e-174 type I (pKG13, pKG59), 436 aa. 1 . . . 426
343/428 (79%) [JP59125896-A, 20-JUL-1984]
[0384] In a BLAST search of public sequence datbases, the NOV12a
protein was found to have homology to the proteins shown in the
BLASTP data in Table 12E. TABLE-US-00067 TABLE 12E Public BLASTP
Results for NOV12a Protein NOV12a Identities/ Accession
Residues/Match Similarities for Expect Number
Protein/Organism/Length Residues the Matched Portion Value KGHUL1
kininogen, LMW precursor 1 . . . 398 396/428 (92%) 0.0 [validated]
- human, 427 aa. 1 . . . 427 396/428 (92%) P01042 Kininogen
precursor 1 . . . 396 375/426 (88%) 0.0 (Alpha-2-thiol proteinase 1
. . . 416 376/426 (88%) inhibitor) [Contains: Bradykinin] - Homo
sapiens (Human), 644 aa. P01046 Kininogen, LMW I precursor 1 . . .
398 297/428 (69%) e-173 (Thiol proteinase inhibitor) 1 . . . 426
343/428 (79%) [Contains: Bradykinin] - Bos taurus (Bovine), 436 aa.
P01047 Kininogen, LMW II precursor 1 . . . 398 292/428 (68%) e-170
(Thiol proteinase inhibitor) 1 . . . 424 340/428 (79%) [Contains:
Bradykinin] - Bos taurus (Bovine), 434 aa. P01044 Kininogen, HMW I
precursor 1 . . . 375 280/405 (69%) e-161 (Thiol proteinase
inhibitor) 1 . . . 403 321/405 (79%) [Contains: Bradykinin] - Bos
taurus (Bovine), 621 aa.
[0385] PFam analysis predicts that the NOV12a protein contains the
domains shown in the Table 12F. TABLE-US-00068 TABLE 12F Domain
Analysis of NOV12a Identities/ Pfam NOV12a Similarities for Expect
Domain Match Region the Matched Region Value cystatin 21 . . . 59
11/40 (28%) 1.9e-06 35/40 (88%) cystatin 60 . . . 97 14/40 (35%)
4e-07 30/40 (75%) cystatin 115 . . . 219 28/113 (25%) 5e-35 92/113
(81%) cystatin 237 . . . 341 32/113 (28%) 3.4e-39 94/113 (83%)
Example 13
[0386] The NOV13 clone was analyzed, and the nucleotide and encoded
polypeptide sequences are shown in Table 13A. TABLE-US-00069 TABLE
13A NOV13 Sequence Analysis SEQ ID NO: 85 1272 bp NOV13a,
CTTCCCCAGGACTCCAGGAGACATAAAACTTGAAACGGGAGACTTCGTGCAAATCCTG
CG105982-01
CTCCGGACGCTGCTGAAGCTCAGATTTCTCCCACTGCCTGCACAGGGTGCTGCCTGCT DNA
GGCGAATGTGACTCTCCTCCTGTTCACCCACAAGGCTGATTTTTCCGTGTTCCTCCTC Sequence
TGGAAAGAGCATTGCTTTCTCTCTTCCAGCACTTTACCTACATTCATGTCTTTCAGGT
GGCTGCTTCTCTATTATGCTCTGTGCTTCTCCCTGTCAAAGGCTTCAGCCCACACCGT
GGAGCTAAACAATATGTTTGGCCAGATCCAGTCGCCTGGTTATCCAGACTCCTATCCC
AGTGATTCAGAGGTGACTTGGAATATCACTGTCCCAGATGGGTTTCGGATCAAGCTTT
ACTTCATGCACTTCAACTTGGAATCCTCCTACCTTTGTGAATATGACTATGTGAAGGT
AGAAACTGAGGACACTTCGAGAGTGCCAAATGACAAGTGGTTTGGGAGTGGGGCCCTG
CTCTCTGCGTCCTGGATCCTCACAGCAGCTCATGTGCTGCGCTCCCAGCGTAGAGACA
CCACGGTGATACCAGTCTCCAAGGAGCATGTCACCGTCTACCTGGGCTTGCATGATGT
GCGAGACAAATCGGGGGCAGTCAACAGCTCAGCTGCCCGAGTGGTGCTCCACCCAGAC
TTCAACATCCAAAACTACAACCACGATATAGCTCTGGTGCAGCTGCAGGAGCCTGTGC
CCCTGGGACCCCACGTTATGCCTGTCTGCCTGCCAAGGCTTGAGCCTGAAGGCCCGGC
CCCCCACATGCTGGGCCTGGTGGCCGGCTGGGGCATCTCCAATCCCAATGTGACAGTG
GATGAGATCATCAGCAGTGGCACACGGACCTTGTCAGATGTCCTGCAGTATGTCAAGT
TACCCGTGGTGCCTCACGCTGAGTGCAAAACTAGCTATGAGTCCCGGTCGGGCAATTA
CAGCGTCACGGAGAACATGTTCTGTGCTGGCTACTACGAGGGCGGCAAAGACACGTGC
CTTGGAGATAGCGGTGGGGCCTTTGTCATCTTTGATGACTTGAGCCAGCGCTGGGTGG
TGCAAGGCCTGGTGTCCTGGGGGGGACCTGAAGAATGCGGCAGCAAGCAGGTCTATGG
AGTCTACACAAAGGTCTCCAATTACGTGGACTGGGTGTGGGAGCAGATGGGCTTACCA
CAAAGTGTTGTGGAGCCCCAGGTGGAACGGTGAGCTGACTTACTTCCTCGCGGG ORF Start:
ATG at 220 ORF Stop: TGA at 1249 SEQ ID NO: 86 343 aa MW at
38275.9kD NOV13a,
MSFRWLLLYYALCFSLSKASAHTVELNNMFGQIQSPGYPDSYPSDSEVTWNITVPDGF
CG105982-01
RIKLYFMHFNLESSYLCEYDYVKVETEDTSRVPNDKWFGSGALLSASWILTAAHVLRS Protein
QRRDTTVIPVSKEHVTVYLGLHDVRDKSGAVNSSAARVVLHPDFNIQNYNHDIALVQL Sequence
QEPVPLGPHVMPVCLPRLEPEGPAPHMLGLVAGWGISNPNVTVDEIISSGTRTLSDVL
QYVKLPVVPHAECKTSYESRSGNYSVTENMFCAGYYEGGKDTCLGDSGGAFVIFDDLS
QRWVVQGLVSWGGPEECGSKQVYGVYTKVSNYVDWVWEQMGLPQSVVEPQVER
[0387] Further analysis of the NOV13a protein yielded the following
properties shown in Table 13B. TABLE-US-00070 TABLE 13B Protein
Sequence Properties NOV13a PSort 0.3700 probability located in
outside; 0.1900 analysis: probability located in lysosome (lumen);
0.1000 probability located in endoplasmic reticulum (membrane);
0.1000 probability located in endoplasmic reticulum (lumen) SignalP
Cleavage site between residues 22 and 23 analysis:
[0388] A search of the NOV13a protein against the Geneseq database,
a proprietary database that contains sequences published in patents
and patent publication, yielded several homologous proteins shown
in Table 13C. TABLE-US-00071 TABLE 13C Geneseq Results for NOV13a
NOV13a Identities/ Geneseq Protein/Organism/Length Residues/Match
Similarities for Expect Identifier [Patent #, Date] Residues the
Matched Region Value AAB85060 Human serine protease MASP-3 82 . . .
343 259/262 (98%) e-154 polypeptide - Homo sapiens, 728 467 . . .
728 260/262 (98%) aa. [WO200140451-A2, 07-JUN-2001] AAB47559
Protease PRTS-1 - Homo sapiens, 82 . . . 343 258/262 (98%) e-153
728 aa. [WO200171004-A2, 467 . . . 728 259/262 (98%) 27-SEP-2001]
AAB84203 Amino acid sequence of a human 82 . . . 332 248/251 (98%)
e-148 serine protease designated Zfaix1 - 19 . . . 269 249/251
(98%) Homo sapiens, 269 aa. [WO200138501-A2, 31-MAY-2001] AAG00221
Human secreted protein, SEQ ID 4 . . . 82 79/79 (100%) 3e-42 NO:
4302 - Homo sapiens, 97 aa. 2 . . . 80 79/79 (100%) [EP1033401-A2,
06-SEP-2000] AAB60935 Horseshoe crab recombinant Factor 92 . . .
326 90/244 (36%) 2e-37 C #2 - Carcinoscorpius 787 . . . 1015
127/244 (51%) rotundicauda, 1019 aa. [WO200127289-A2,
19-APR-2001]
[0389] In a BLAST search of public sequence datbases, the NOV13a
protein was found to have homology to the proteins shown in the
BLASTP data in Table 13D. TABLE-US-00072 TABLE 13D Public BLASTP
Results for NOV13a Protein NOV13a Identities/ Accession
Residues/Match Similarities for Expect Number
Protein/Organism/Length Residues the Matched Portion Value CAC42682
SEQUENCE 1 FROM PATENT 82 . . . 343 259/262 (98%) e-154 WO0140451 -
Homo sapiens 467 . . . 728 260/262 (98%) (Human), 728 aa. Q96RS4
COMPLEMENT FACTOR MASP-3 - 82 . . . 343 259/262 (98%) e-154 Homo
sapiens (Human), 728 aa. 467 . . . 728 260/262 (98%) CAC42545
SEQUENCE 1 FROM PATENT 82 . . . 332 248/251 (98%) e-147 WO0138501 -
Homo sapiens 19 . . . 269 249/251 (98%) (Human), 269 aa (fragment).
Q920S0 MBL-ASSOCIATED SERINE 82 . . . 343 236/262 (90%) e-141
PROTEASE-3 - Mus musculus 472 . . . 733 247/262 (94%) (Mouse), 733
aa. Q9PVY2 MANNOSE-BINDING LECTIN- 82 . . . 330 158/251 (62%) 9e-93
ASSOCIATED SERINE 465 . . . 714 198/251 (77%) PROTEASE - Triakis
scyllium (Leopard shark) (Triakis scyllia), 719 aa.
[0390] PFam analysis predicts that the NOV13a protein contains the
domains shown in the Table 13E. TABLE-US-00073 TABLE 13E Domain
Analysis of NOV13a Identities/ Pfam NOV13a Similarities for Expect
Domain Match Region the Matched Region Value CUB 22 . . . 134
37/127 (29%) 1.5e-05 75/127 (59%) Trypsin 94 . . . 326 86/258 (33%)
2.2e-66 192/258 (74%)
Example 14
[0391] The NOV14 clone was analyzed, and the nucleotide and encoded
polypeptide sequences are shown in Table 14A. TABLE-US-00074 TABLE
14A NOV14 Sequence Analysis SEQ ID NO: 87 861 bp NOV14a,
CAGCTCAGCATGGCTAGGGTACTGGGAGCACCCGTTGCACTGGGGTTGTGGAGCCTAT
CG107614-02
GCTGGTCTCTGGCCATTGCCACCCCTCTTCCTCCGACTAGTGCCCATGGGAATGTTGC DNA
TGAAGGCGAGACCAAGCCAGACCCAGACGTGACTGAACGCTGCTCAGATGGCTGGAGC Sequence
TTTGATGCTACCACCCTGGATGACAATGGAACCATGCTGTTTTTTAAAGGGACCCACT
ACTGGCGTCTGGACACCAGCCGGGATGGCTGGCATAGCTGGCCCATTGCTCATCAGTG
GCCCCAGGGTCCTTCAGCAGTGGATGCTGCCTTTTCCTGGGAAGAAAAACTCTATCTG
GTCCAGGGCACCCAGGTATATGTCTTCCTGACAAAGGGAGGCTATACCCTAGTAAGCG
GTTATCCGAAGCGGCTGGAGAAGGAAGTCGGGACCCCTCATGGGATTATCCTGGACTC
TGTGGATGCGGCCTTTATCTGCCCTGGGTCTTCTCGGCTCCATATCATGGCAGGACGG
CGGCTGTGGTGGCTGGAGCTGAAGTCAGGAGCCCAAGCCACGTGGACAGAGCTTCCTT
GGCCCCATGAGAAGGTAGACGGAGCCTTGTGTATGGAAAAGTCCCTTGGCCCTAACTC
ATGTTCCGCCAATGGTCCCGGCTTGTACCTCATCCATGGTCCCAATTTGTACTGCTAC
AGTGATGTGGAGAAACTGAATGCAGCCAAGGCCCTTCCGCAACCCCAGAATGTGACCA
GTCTCCTGGGCTGCACTCACTGAGGGGCCTTCTGACATGAGTCTGGCCTGGCCCCACC
TCCTAGTTCCTCATAATAAAGACAGATTGCTTCTTCGCTTCTCACTGAG ORF Start: ATG at
10 ORF Stop: TGA at 775 SEQ ID NO: 88 255 aa MW at 27921.4kD
NOV14a, MARVLGAPVALGLWSLCWSLAIATPLPPTSAHGNVAEGETKPDPDVTERCSDGWSFDA
CG107614-02
TTLDDNGTMLFFKGTHYWRLDTSRDGWHSWPIAHQWPQGPSAVDAAFSWEEKLYLVQG Protein
TQVYVFLTKGGYTLVSGYPKRLEKEVGTPHGIILDSVDAAFICPGSSRLHIMAGRRLW Sequence
WLDLKSGAQATWTELPWPHEKVDGALCMEKSLGPNSCSANGPGLYLIHGPNLYCYSDV
EKLNAAKALPQPQNVTSLLGCTH
[0392] Further analysis of the NOV14a protein yielded the following
properties shown in Table 14B. TABLE-US-00075 TABLE 14B Protein
Sequence Properties NOV14a PSort 0.4586 probability located in
lysosome (lumen); 0.4323 analysis: probability located in outside;
0.3077 probability located in microbody (peroxisome); 0.1000
probability located in endoplasmic reticulum (membrane) SignalP
Cleavage site between residues 32 and 33 analysis:
[0393] A search of the NOV14a protein against the Geneseq database,
a proprietary database that contains sequences published in patents
and patent publication, yielded several homologous proteins shown
in Table 14C. TABLE-US-00076 TABLE 14C Geneseq Results for NOV14a
NOV14a Identities/ Residues/ Similarities for Geneseq
Protein/Organism/Length Match the Matched Expect Identifier [Patent
#, Date] Residues Region Value AAM23933 Human EST encoded protein
SEQ ID 30 . . . 255 197/226 (87%) e-116 NO: 1458 - Homo sapiens,
462 aa. 242 . . . 462 201/226 (88%) [WO200154477-A2, 02-AUG-2001]
AAG00304 Human secreted protein, SEQ ID 1 . . . 77 73/77 (94%)
5e-39 NO: 4385 - Homo sapiens, 83 aa. 1 . . . 77 74/77 (95%)
[EP1033401-A2, 06-SEP-2000] AAP93630 Sequence of rat transin - 43 .
. . 179 45/142 (31%) 2e-08 Rattus rattus, 463 aa. 270 . . . 401
68/142 (47%) [GB2209526-A, 17-MAY-1989] AAM48977 Human matrix
metalloproteinase 30 . . . 177 38/150 (25%) 4e-07 13 (collagenase
3) - Homo sapiens, 264 . . . 406 68/150 (45%) 471 aa.
[WO200206294-A2, 24- JAN-2002] AAB84615 Amino acid sequence of
matrix 30 . . . 177 38/150 (25%) 4e-07 metalloproteinase-13 - 264 .
. . 406 68/150 (45%) Homo sapiens, 471 aa. [WO200149309-A2,
12-JUL-2001]
[0394] In a BLAST search of public sequence datbases, the NOV14a
protein was found to have homology to the proteins shown in the
BLASTP data in Table 14D. TABLE-US-00077 TABLE 14D Public BLASTP
Results for NOV14a NOV14a Identities/ Protein Residues/
Similarities for Accession Match the Matched Expect Number
Protein/Organism/Length Residues Portion Value P02790 Hemopexin
precursor (Beta-1B- 30 . . . 255 197/226 (87%) e-116 glycoprotein)
- Homo sapiens 242 . . . 462 201/226 (88%) (Human), 462 aa. OQRB
hemopexin precursor - rabbit, 28 . . . 255 167/228 (73%) e-100 459
aa. 233 . . . 459 186/228 (81%) P20058 Hemopexin precursor - 28 . .
. 255 167/228 (73%) e-100 Oryctolagus cuniculus (Rabbit), 234 . . .
460 186/228 (81%) 460 aa. P20059 Hemopexin precursor - 30 . . . 254
159/225 (70%) 7e-96 Rattus norvegicus (Rat), 460 aa. 242 . . . 459
183/225 (80%) P50828 Hemopexin precursor 48 . . . 253 152/206 (73%)
2e-95 (Hyaluronidase) (EC 3.2.1.35) - 248 . . . 453 175/206 (84%)
Sus scrofa (Pig), 459 aa.
[0395] PFam analysis predicts that the NOV14a protein contains the
domains shown in the Table 14E. TABLE-US-00078 TABLE 14E Domain
Analysis of NOV14a Identities/ Similarities for the Matched Expect
Pfam Domain NOV14a Match Region Region Value hemopexin 56 . . . 99
17/50 (34%) 1.4e-09 31/50 (62%) hemopexin 101 . . . 146 14/50 (28%)
4.5e-07 37/50 (74%)
Example 15
[0396] The NOV15 clone was analyzed, and the nucleotide and encoded
polypeptide sequences are shown in Table 15A. TABLE-US-00079 TABLE
15A NOV15 Sequence Analysis SEQ ID NO: 89 2671 bp NOV15a,
CCCGCCGGGCGAGCATGGGGCGCCTGGCCTCGAGGCCGCTGCTGCTGGCGCTCCTGTC
CG109445-01
GTTGGCTCTTTGCCGAGGGCGTGTGGTGAGAGTCCCCACAGCGACCCTGGTTCGAGTG DNA
GTGGGCACTGAGCTGGTCATCCCCTGCAACGTCAGTGACTATGATGGCCCCAGCGAGC Sequence
AAAACTTTGACTGGAGCTTCTCATCTTTGGGGAGCAGCTTTGTGGAGCTTGCAAGCAC
CTGGGAGGTGGGGTTCCCAGCCCAACTGTACCAGGAGCGGCTGCAGAGGGGCGAGATC
CTGTTAAGGCGGACTGCCAACGACGCCGTGGAGCTCCACATAAAGAACGTCCAGCCTT
CAGACCAAGGCCACTACAAATGTTCAAGCCCCAGCACAGATGCCACTGTCCAGGGAAA
CTATGAGGACACAGTGCAGGTTAAAGTGCTGGCCGACTCCCTGCACGTGGGCCCCAGC
GCGCGGCCCCCGCCGAGCCTGAGCCTGCGGGAGGGGGAGCCCTTCGAGCTGCGCTGCA
CCGCCGCCTCCGCCTCGCCGCTGCACACGCACCTGGCGCTGCTGTGGGAGGTGCACCG
CGGCCCGGCCAGGCGGAGCGTCCTCGCCCTGACCCACGAGGGCAGGTTCCACCCGGGC
CTGGGGTACGAGCAGCGCTACCACAGTGGGGACGTGCGCCTCGACACCGTGGGCAGCG
ACGCCTACCGCCTCTCAGTGTCCCGGGCTCTGTCTGCCGACCAGGGCTCCTACAGGTG
TATCGTCAGCGAGTGGATCGCCGAGCAGGGCAACTGGCAGGAAATCCAAGAAAAGGCC
GTGGAAGTTGCCACCGTGGTGATCCAGCCGACAGTTCTGCGAGCAGCCGTGCCCAAGA
ATGTGTCTGTGGCTGAAGGAAAGGAACTGGACCTGACCTGTAACATCACAACAGACCG
AGCCGATGACGTCCGGCCCGAGGTGACGTGGTCCTTCAGCAGGATGCCTGACAGCACC
CTACCTGGCTCCCGCGTGTTGGCGCGGCTTGACCGTGATTCCCTGGTGCACAGCTCGC
CTCATGTTGCTTTGAGTCATGTGGATGCACGCTCCTACCATTTACTGGTTCGGGATGT
TAGCAAAGAAAACTCTGGCTACTATTACTGCCACGTGTCCCTGTGGGCACCCGGACAC
AACAGGAGCTGGCACAAAGTGGCAGAGGCCGTGTCTTCCCCAGCTGGTGTGGGTGTGA
CCTGGCTAGAACCAGACTACCAGGTGTACCTGAATGCTTCCAAGGTCCCCGGGTTTGC
GGATGACCCCACAGAGCTGGCATGCCGGGTGGTGGACACGAAGAGTGGGGAGGCGAAT
GTCCGATTCACGGTTTCGTGGTACTACAGGATGAACCGGCGCAGCGACAATGTGGTGA
CCAGCGAGCTGCTTGCAGTCATGGACGGGGACTGGACGCTAAAATATGGAGAGAGGAG
CAAGCAGCGGGCCCAGGATGGAGACTTTATTTTTTCTAAGGAACATACAGACACGTTC
AATTTCCGGATCCAAAGGACTACAGAGGAAGACAGAGGCAATTATTACTGTGTTGTGT
CTGCCTGGACCAAACAGCGGAACAACAGCTGGGTGAAAAGCAAGGATGTCTTCTCCAA
GCCTGTTAACATATTTTGGGCATTAGAAGATTCCGTGCTTGTGGTGAAGGCGAGGCAG
CCAAAGCCTTTCTTTGCTGCCGGAAATACATTTGAGATGACTTGCAAAGTATCTTCCA
AGAATATTAAGTCGCCACGCTACTCTGTTCTCATCATGGCTGAGAAGCCTGTCGGCGA
CCTCTCCAGTCCCAATGAAACGAAGTACATCATCTCTCTGGACCAGGATTCTGTGGTG
AAGCTGGAGAATTGGACAGATGCATCACGGGTGGATGGCGTTGTTTTAGAAAAAGTGC
AGGAGGATGAGTTCCGCTATCGAATGTACCAGACTCAGGTCTCAGACGCAGGGCTGTA
CCGCTGCATGGTGACAGCCTGGTCTCCTGTCAGGGGCAGCCTTTGGCGAGAAGCAGCA
ACCAGTCTCTCCAATCCTATTGAGATAGACTTCCAAACCTCAGGTCCTATATTTAATG
CTTCTGTGCATTCAGACACACCATCAGTAATTCGGGGAGATCTGATCAAATTGTTCTG
TATCATCACTGTCGAGGGAGCAGCACTGGATCCAGATGACATGGCCTTTGATGTGTCC
TGGTTTGCGGTGCACTCTTTTGGCCTGGACAAGGCTCCTGTGCTCCTGTCTTCCCTGG
ATCGGAAGGGCATCGTGACCACCTCCCGGAGGGACTGGAAGAGCGACCTCAGCCTGGA
GCGCGTGAGTGTGCTGGAATTCTTGCTGCAAGTGCATGGCTCCGAGGACCAGGACTTT
GGCAACTACTACTGTTCCGTGACTCCATGGGTGAAGTCACCAACAGGTTCCTGGCAGA
AGGAGGCAGAGATCCACTCCAAGCCCGTTTTTATAACTGTGAAGATGGATGTGCTGAA
CGCCTTCAAGTATCCCTTGCTGATCGGCGTCGGTCTGTCCACGGTCATCGGGCTCCTG
TCCTGTCTCATCGGGTACTGCAGCTCCCACTGGTGTTGTAAGAAGGAGGTTCAGGAGA
CACGGCGCGAGCGCCGCAGGCTCATGTCGATGGAGATGGACTAGGCTGGCCCGGGAGG GGA ORF
Start: ATG at 15 ORF Stop: TAG at 2652 SEQ ID NO: 90 879 aa MW at
98569.4kD NOV15a,
MGRLASRPLLLALLSLALCRGRVVRVPTATLVRVVGTELVIPCNVSDYDGPSEQNFDW
CG109445-01
SFSSLGSSFVELASTWEVGFPAQLYQERLQRGETLLRRTANDAVELHIKNVQPSDQGH Protein
YKCSTPSTDATVQGNYEDTVQVKVLADSLHVGPSARPPPSLSLREGEPFELRCTAASA Sequence
SPLHTHLALLWEVHRGPARRSVLALTHEGRFHFGLGYEQRYHSGDVRLDTVGSDAYRL
SVSRALSADQGSYRCIVSEWIAEQGNWQEIQEKAVEVATVVIQPTVLRAAVPKNVSVA
EGKELDLTCNITTDRADDVRPEVTWSFSRMPDSTLPGSRVLARLDRDSLVHSSPEVAL
SHVDARSYHLLVRDVSKENSGYYYCHVSLWAPGHNRSWHKVAEAVSSPAGVGVTWLEP
DYQVYLNASKVPGFADDPTELACRVVDTKSGEANVRFTVSWYYRMNRRSDNVVTSELL
AVMDGDWTLKYGERSKQRAQDGDFIFSKEHTDTFNFRIQRTTEEDRGNYYCVVSAWTK
QRNNSWVKSKDVFSKPVNIFWALEDSVLVVKARQPKPFFAAGNTFEMTCKVSSKNIKS
PRYSVLIMAEKPVGDLSSPNETKYIISLDQDSVVKLENWTDASRVDGVVLEKVQEDEF
RYRNYQTQVSDAGLYRCMVTAWSPVRGSLWREAATSLSNFIEIDFQTSGPIFNASVHS
DTPSVIRGDLIKLFCIITVEGAALDPDDMAFDVSWFAVHSFGLDKAPVLLSSLDRKGI
VTTSRRDWKSDLSLERVSVLEFLLQVHGSEDQDFGNYYCSVTPWVKSPTGSWQKEAEI
HSKPVFITVKMDVLNAFKYPLLIGVGLSTVIGLLSCLIGYCSSHWCCKKEVQETRRER
RRLMSMEMD
[0397] Further analysis of the NOV15a protein yielded the following
properties shown in Table 15B. TABLE-US-00080 TABLE 15B Protein
Sequence Properties NOV15a PSort 0.6800 probability located in
lysosome (membrane); 0.5140 analysis: probability located in plasma
membrane; 0.1760 probability located in microbody (peroxisome);
0.1000 probability located in endoplasmic reticulum (membrane)
SignalP Cleavage site between residues 26 and 27 analysis:
[0398] A search of the NOV15a protein against the Geneseq database,
a proprietary database that contains sequences published in patents
and patent publication, yielded several homologous proteins shown
in Table 15C. TABLE-US-00081 TABLE 15C Geneseq Results for NOV15a
NOV15a Identities/ Residues/ Similarities for Geneseq
Protein/Organism/Length Match the Matched Expect Identifier [Patent
#, Date] Residues Region Value AAM93277 Human polypeptide, SEQ ID
NO: 1 . . . 863 862/863 (99%) 0.0 2751 - Homo sapiens, 863 aa. 1 .
. . 863 862/863 (99%) [EP1130094-A2, 05-SEP-2001] ABB11196 Human PG
F2a receptor regulator 236 . . . 372 131/137 (95%) 7e-70 homologue,
SEQ ID NO: 1566 - 2 . . . 138 132/137 (95%) Homo sapiens, 138 aa.
[WO200157188-A2, 09-AUG-2001] ABB10996 Human prostaglandin receptor
500 . . . 625 117/126 (92%) 3e-60 regulator homologue, SEQ ID NO: 1
. . . 126 118/126 (92%) 1366 - Homo sapiens, 126 aa.
[WO200157188-A2, 09-AUG-2001] AAB90544 Human secreted protein, SEQ
ID 6 . . . 542 163/565 (28%) 2e-59 NO: 82 - Homo sapiens, 613 aa.
12 . . . 571 260/565 (45%) [WO200121658-A1, 29-MAR-2001] AAM24248
Human EST encoded protein SEQ ID 6 . . . 542 163/565 (28%) 2e-59
NO: 1773 - Homo sapiens, 613 aa. 12 . . . 571 260/565 (45%)
[WO200154477-A2, 02-AUG-2001]
[0399] In a BLAST search of public sequence datbases, the NOV15a
protein was found to have homology to the proteins shown in the
BLASTP data in Table 15D. TABLE-US-00082 TABLE 15D Public BLASTP
Results for NOV15a NOV15a Identities/ Protein Residues/
Similarities for Accession Match the Matched Expect Number
Protein/Organism/Length Residues Portion Value Q9P2B2 KIAA1436
PROTEIN - 1 . . . 879 878/879 (99%) 0.0 Homo sapiens (Human), 924
46 . . . 924 879/879 (99%) aa (fragment). Q9WV91 F2 ALPHA
PROSTOGLANDIN 1 . . . 879 786/879 (89%) 0.0 REGULATORY PROTEIN - 1
. . . 879 830/879 (94%) Mus musculus (Mouse), 879 aa. Q62786
Prostaglandin F2-alpha receptor 1 . . . 879 784/879 (89%) 0.0
regulatory protein precursor 1 . . . 879 834/879 (94%)
(Prostaglandin F2-alpha receptor associated protein) - Rattus
norvegicus (Rat), 879 aa. Q9H3U3 SMAP-6 - Homo sapiens (Human), 694
. . . 879 186/186 (100%) e-106 186 aa (fragment). 1 . . . 186
186/186 (100%) O02834 ADIPOCYTE MEMBRANE 690 . . . 879 184/190
(96%) e-105 PROTEIN - Sus scrofa (Pig), 1 . . . 190 186/190 (97%)
190 aa (fragment).
[0400] PFam analysis predicts that the NOV15a protein contains the
domains shown in the Table 15E. TABLE-US-00083 TABLE 15E Domain
Analysis of NOV15a Identities/ Similarities for Pfam the Matched
Expect Domain NOV15a Match Region Region Value ig 36 . . . 121
15/87 (17%) 0.0013 52/87 (60%) ig 162 . . . 249 13/89 (15%) 0.00048
60/89 (67%) ig 292 . . . 375 16/85 (19%) 5.8e-07 58/85 (68%) ig 422
. . . 517 16/97 (16%) 2.3e-06 72/97 (74%) ig 564 . . . 65 7 12/97
(12%) 1.2e-05 64/97 (66%) ig 704 . . . 795 11/93 (12%) 0.19 55/93
(59%)
Example 16
[0401] The NOV16 clone was analyzed, and the nucleotide and encoded
polypeptide sequences are shown in Table 16A. TABLE-US-00084 TABLE
16A NOV16 Sequence Analysis SEQ ID NO: 91 1565bp NOV16a,
GGAATGCTCTCCCGCCTGAGCCTGCTCCAGGAATTGGACCTCAGCTACAACCAGCTCT
CG109496-01
CAACCCTTGAGCCTGGGGCCTTCCATGGCCTACAAAGCCTACTCACCCTGAGGCTGCA DNA
GGGCAATCGGCTCAGAATCATGGGGCCTGGGGTCTTCTCAGGCCTCTCTGCTCTGACC Sequence
CTGCTGGACCTCCGCCTCAACCAGATTGTTCTCTTCCTAGATGGAGCTTTTGGGGAGC
TAGGCAGCCTCCAGAAGCTGGAGGTTGGGGACAACCACCTGGTATTTGTGGCTCCGGG
GGCCTTTGCAGGGCTAGCCAAGTTGAGCACCCTCACCCTGGAGCGCTGCAACCTCAGC
ACAGTGCCTGGCCTAGCCCTTGCCCGTCTCCCGGCACTAGTGGCCCTAAGGCTTAGAG
AACTGGATATTGGGAGGCTGCCAGCTGGGGCCCTGCGGGGGCTGGGGCAGCTCAAGGA
GCTGGAGATCCACCTCTGGCCATCTCTGGAGGCTCTGGACCCTGGGAGCCTGGTTGGG
CTCAATCTCAGCAGCCTGGCCATCACTCGCTGCAATCTGAGCTCGGTGCCCTTCCAAG
CACTGTACCACCTCAGCTTCCTCAGGGTCCTGGATCTGTCCCAGAATCCCATCTCAGC
CATCCCAGCCCGAAGGCTCAGCCCCCTGGTGCGGCTCCAGGAGCTACGCCTGTCAGGG
GCATGCCTCACCTCCATTGCTGCCCATGCCTTCCATGGCTTGACTGCCTTCCACCTCC
TGGATGTGGCAGATAACGCCCTTCAGACACTAGAGGAAACAGCTTTCCCTTCTCCAGA
CAAACTGGTCACCTTGAGGCTGTCTGGCAACCCCCTAACCTGTGACTGCCGCCTCCTC
TGGCTGCTCCGGCTCCGCCGCCACCTGGACTTTGGCATGTCCCCCCCTGCCTGTGCTG
GCCCCCATCATGTCCAGGGGAAGAGCCTGAAGGAGTTTTCAGACATCCTGCCTCCAGG
GCACTTCACCTGCAAACCAGCCCTGATCCGAAAGTCGGGGCCTCGATGGGTCATTGCA
GAGGAGGGCGGGCATGCGGTTTTCTCCTGCTCTGGAGATGGAGACCCAGCCCCCACTG
TCTCCTGGATGAGGCCTCATGGGGCTTGGCTGGGCAGGGCTGGGAGAGTAAGGGTCCT
AGAGGATGGGACACTGGAGATCCGCTCAGTGCAGCTACGGGACAGAGGGGCCTATGTC
TGTGTGGTTAGCAATGTCGCTGGGAATGACTCCCTGAGGACCTGGCTGGAAGTCATCC
AGGTGGAACCACCAAACGGCACACTTTCTGACCCCAACATCACCGTGCCAGGGATCCC
AGGGCCTTTTTTTCTGGATAGCAGAGGTGTGGCCATGGTGCTGGCAGTGGGCTTCCTC
CCCTTCCTCACCTCAGTGACCCTCTGCTTTGGCCTGATTGCCCTTTGGAGCAAGGGCA
AAGGTCGGGTCAAACATCACATGACCTTTGACTTTGTGGCACCTCGGCCCTCTGGGGA
TAAAAACTCTGGGGGTAACCGGGTCACTGCCAAGCTCTTCTGACCTTTCCTTCCCCA ORF
Start: ATG at 4 ORF Stop: TGA at 1549 SEQ ID NO: 92 515 aa MW at
55659.0kD NOV16a,
MLSRLSLLQELDLSYNQLSTLEPGAFHGLQSLLTLRLQGNRLRIMGPGVFSGLSALTL
CG109496-01
LDLRLNQIVLFLDGAFGELGSLQKLEVGDNHLVFVAPGAFAGLAKLSTLTLERCNLST Protein
VPGLALARLPALVALRLRELDIGRLPAGALRGLGQLKELEIHLWPSLEALDPGSLVGL Sequence
NLSSLAITRCNLSSVPFQALYHLSFLRVLDLSQNPISAIPARRLSPLVRLQELRLSGA
CLTSIAAHAFHGLTAFHLLDVADNALQTLEETAFPSPDKLVTLRLSGNPLTCDCRLLW
LLRLRRHLDFGMSPPACAGPHHVQGKSLKEFSDILPPGHFTCKPALIRKSGPRWVIAE
EGGHAVFSCSGDGDPAPTVSWMRPHGAWLGRAGRVRVLEDGTLEIRSVQLRDRGAYVC
VVSNVAGNDSLRTWLEVIQVEPPNGTLSDPNITVPGIPGPFFLDSRGVAMVLAVGFLP
FLTSVTLCFGLIALWSKGKGRVKHHMTFDFVAPRPSGDKNSGGNRVTAKLF
[0402] Further analysis of the NOV16a protein yielded the following
properties shown in Table 16B. TABLE-US-00085 TABLE 16B Protein
Sequence Properties NOV16a PSort 0.7000 probability located in
plasma membrane; 0.5204 analysis: probability located in
mitochondrial inner membrane; 0.4430 probability located in
microbody (peroxisome); 0.2217 probability located in mitochondrial
intermembrane space SignalP No Known Signal Sequence Predicted
analysis:
[0403] A search of the NOV16a protein against the Geneseq database,
a proprietary database that contains sequences published in patents
and patent publication, yielded several homologous proteins shown
in Table 16C. TABLE-US-00086 TABLE 16C Geneseq Results for NOV16a
NOV16a Identities/ Residues/ Similarities for Geneseq
Protein/Organism/Length Match the Matched Expect Identifier [Patent
#, Date] Residues Region Value AAW84596 Amino acid sequence of the
human 8 . . . 500 229/509 (44%) e-116 Tango-79 protein - Homo
sapiens, 91 . . . 596 312/509 (60%) 614 aa. [WO9906427-A1, 11-FEB-
1999] AAB74705 Human membrane associated protein 8 . . . 500
228/509 (44%) e-116 MEMAP-11 - Homo sapiens, 620 aa. 97 . . . 602
312/509 (60%) [WO2001 12662-A2, 22-FEB-2001] AAB80225 Human PRO227
protein - 8 . . . 500 227/509 (44%) e-115 Homo sapiens, 620 aa. 97
. . . 602 311/509 (60%) [WO200104311-Al, 18-JAN-2001] AAU12333
Human PRO227 polypeptide sequence - 8 . . . 500 227/509 (44%) e-115
Homo sapiens, 620 aa. 97 . . . 602 311/509 (60%) [WO200140466-A2,
07-JUN-2001] AAY13357 Amino acid sequence of protein 8 . . . 500
227/509 (44%) e-115 PRO227 - Homo sapiens, 620 aa. 97 . . . 602
311/509 (60%) [WO9914328-A2, 25-MAR-1999]
[0404] In a BLAST search of public sequence datbases, the NOV16a
protein was found to have homology to the proteins shown in the
BLASTP data in Table 16D. TABLE-US-00087 TABLE 16D Public BLASTP
Results for NOV16a NOV16a Identities/ Protein Residues/
Similarities for Accession Match the Matched Expect Number
Protein/Organism/Length Residues Portion Value Q9N008 HYPOTHETICAL
69.2 KDA 8 . . . 500 228/509 (44%) e-115 PROTEIN - Macaca
fascicularis 91 . . . 596 312/509 (60%) (Crab eating macaque)
(Cynomolgus monkey), 614 aa. Q96FE5 UNKNOWN (PROTEIN FOR 8 . . .
500 228/509 (44%) e-115 MGC: 17422) - Homo sapiens 91 . . . 596
312/509 (60%) (Human), 614 aa. Q9D1T0 ADULT MALE TESTIS CDNA, 8 . .
. 500 228/509 (44%) e-115 RIKEN FULL-LENGTH ENRICHED 91 . . . 596
312/509 (60%) LIBRARY, CLONE: 4930471K13, FULL INSERT SEQUENCE -
Mus musculus (Mouse), 614 aa. Q9BZ20 BA438B23.1 (NEURONAL 7 . . .
501 224/507 (44%) e-113 LEUCINE-RICH REPEAT 82 . . . 588 311/507
(61%) PROTEIN) (CDNA FLJ31810 FIS, CLONE NT2RI2009289, WEAKLY
SIMILAR TO CARBOXYPEPTIDASE N 83 KDA CHAIN) - Homo sapiens (Human),
606 aa. CAC34918 SEQUENCE 1 FROM PATENT 7 . . . 501 197/505 (39%)
3e-89 WO0075358 - Homo sapiens 82 . . . 530 278/505 (55%) (Human),
548 aa.
[0405] PFam analysis predicts that the NOV16a protein contains the
domains shown in the Table 16E. TABLE-US-00088 TABLE 16E Domain
Analysis of NOV16a NOV16a Identities/ Match Similarities Pfam
Domain Region for the Matched Region Expect Value LRR 7 . . . 30
13/25 (52%) 3.8e-05 22/25 (88%) LRR 31 . . . 54 8/25 (32%) 0.64
19/25 (76%) LRR 199 . . . 222 9/25 (36%) 0.27 16/25 (64%) LRR 223 .
. . 246 9/25 (36%) 0.32 19/25 (76%) LRRCT 280 . . . 333 19/58 (33%)
3.1e-07 42/58 (72%) ig 350 . . . 408 19/62 (31%) 9.1e-09 41/62
(66%)
Example 17
[0406] The NOV17 clone was analyzed, and the nucleotide and encoded
polypeptide sequences are shown in Table 17A. TABLE-US-00089 TABLE
17A NOV17 Sequence Analysis SEQ ID NO: 93 1780 bp NOV17a,
CCAACCCTCTGCCCGGCCGGTGCCCATGCTTCTGTGGCTGCTGCTGCTGATCCTGACT
CG109532-01
CCTGGAAGAGAACAATCAGGGGTGGCCCCAAAAGCTGTACTTCTCCTCAATCCTCCAT DNA
GGTCCACAGCCTTCAAAGGAGAAAAAGTGGCTCTCATATGCAGCAGCATATCACATTC Sequence
CCTAGCCCAGGGAGACACATATTGGTATCACGATGAGAAGTTGTTGAAAATAAAACAT
GACAAGATCCAAATTACAGAGCCTGGAAATTACCAATGTAAGACCCGAGGATCCTCCC
TCAGTGATGCCGTGCATGTGGAATTTTCACCTGACTGGGTGATCCTGCAGGCTTTACA
TCCTGTCTTTGAAGGAGACAATGTCATTCTGAGATGTCAGGGGAAAGACAACAAAAAC
ACTCATCAAAAGGTTTACTACAAGGATGGAAAACAGCTTCCTAATAGTTATAATTTAG
AGAAGATCACAGTGAATTCAGTCTCCAGGGATAATAGCAAATATCATTGTACTGCTTA
TAGGAAGTTTTACATACTTGACATTGAAGTAACTTCAAAACCCCTAAATATCCAAGTT
CAAGAGCTGTTTCTACATCCTGTGCTGAGAGCCAGCTCTTCCACGCCCATAGAGGGGA
GTCCCATGACCCTGACCTGTGAGACCCAGCTCTCTCCACAGAGGCCAGATGTCCAGCT
GCAATTCTCCCTCTTCAGAGATAGCCAGACCCTCGGATTGGGCTGGAGCAGGTCCCCC
AGACTCCAGATCCCTGCCATGTGGACTGAAGACTCAGGGTCTTACTGGTGTGAGGTGG
AGACAGTGACTCACAGCATCAAAAAAAGGAGCCTGAGATCTCAGATACGTGTACAGAG
AGTCCCTGTGTCTAATGTGAATCTAGAGATCCGGCCCACCGGAGGGCAGCTGATTGAA
GGAGAAAATATGGTCCTTATTTGCTCAGTAGCCCAGGGTTCAGGGACTGTCACATTCT
CCTGGCACAAAGAAGGAAGAGTAAGAAGCCTGGGTAGAAAGACCCAGCGTTCCCTGTT
GGCAGAGCTGCATGTTCTCACCGTGAAGGAGAGTGATGCAGGGAGATACTACTGTGCA
GCTGATAACGTTCACAGCCCCATCCTCAGCACGTGGATTCGAGTCACCGTGAGAATTC
CGGTATGTCACCCTGTCCTCACCTTCAGGGCTCCCAGGGCCCACACTGTGGTGGGGGA
CCTGCTGGAGCTTCACTGTGAGTCCCTGAGAGGCTCTCCCCCGATCCTGTACCGATTT
TATCATGAGGATGTCACCCTGGGGAACAGCTCAGCCCCCTCTGGAGGAGGAGCCTCCT
TCAACCTCTCTCTGACTGCAGAACATTCTGGAAACTACTCCTGTGATGCAGACAATGG
CCTGGGGGCCCAGCACAGTCATGGAGTGAGTCTCAGGGTCACAGTTCCGGTGTCTCGC
CCCGTCCTCACCCTCAGGGCTCCCGGGGCCCAGGCTGTGGTGGGGGACCTGCTGGAGC
TTCACTGTGAGTCCCTGAGAGGCTCCTTCCCGATCCTGTACTGGTTTTATCACGAGGA
TGACACCTTGGGGAACATCTCGGCCCACTCTGGAGGAGGGGCATCCTTCAACCTCTCT
CTGACTACAGAACATTCTGGAAACTACTCATGTGAGGCTGACAATGGCCTGGGGGCCC
AGCACAGTAAAGTGGTGACACTCAATGTTACAGGTGTGTTAATAGTACCTGGGCTAGA
GGTCACAGTTATGGTAAATAAAATAGTTATCTGACAGATT ORF Start: ATG at 26 ORE
Stop: TGA at 1772 SEQ ID NO: 94 582 aa MW at 64270.5kD NOV17a,
MLLWLLLLILTFGREQSGVAPKAVLLLNPPWSTAFKGEKVALICSSISHSLAQGDTYW
CG109532-01
YHDEKLLKIKHDKIQITEPGNYQCKTRGSSLSDAVHVEFSPDWLILQALHPVFEGDNV Protein
ILRCQGKDNKNTHQKVYYKDGKQLPNSYNLEKITVNSVSRDNSKYHCTAYRKFYILDI Sequence
EVTSKPLNIQVQELFLHFVLRASSSTPIEGSPMTLTCETQLSPQRPDVQLQFSLFRDS
QTLGLGWSRSPRLQIPANWTEDSGSYWCEVETVTHSIKKRSLRSQIRVQRVPVSNVNL
EIRPTGGQLIEGENMVLICSVAQGSGTVTFSWHKEGRVRSLGRKTQRSLLAELHVLTV
KESDAGRYYCAADNVHSPILSTWIRVTVRIPVSHPVLTFRAPRAHTVVGDLLELHCES
LRGSPPILYRFYHEDVTLGNSSAPSGGGASFNLSLTAEHSGNYSCDADNGLGAQHSHG
VSLRVTVFVSRPVLTLRAPGAQAVVGDLLELHCESLRGSFPILYWFYHEDDTLGNISA
HSGGGASFNLSLTTEHSGNYSCEADNGLGAQHSKVVTLNVTGVLIVPGLEVTVMVNKI VI SEQ
ID NO: 95 1263 bp NOV17b,
AAGCTTGGAGAAAAAGTGGCTCTCATATGCAGCAGCATATCACATTCCCTAGCCCAGG
207775340
GAGACACATATTGGTATCACGATGAGAAGTTGTTGAAAATAAAACATGACAAGATCCA DNA
AATTACAGAGCCTGGAAATTACCAATGTAAGACCCGAGGATCCTCCCTCAGTGATGCC Sequence
GTGCATGTGGAATTTTCACCTGACTGGCTGATCCTGCAGGCTTTACATCCTGTCTTTG
AAGGAGACAATGTCATTCTGAGATGTCAGGGGAAAGACAACAAAAACACTCATCAAAA
GGTTTACTACAAGGATGGAAAACAGCTTCCTAATAGTTATAATTTAGAGAAGATCACA
GTGAATTCAGTCTCCAGGGATAATAGCAAATATCATTGTACTGCTTATAGGAAGTTTT
ACATACTTGACATTGAAGTAACTTCAAAACCCCTAAATATCCAAGTTCAAGAGCTGTT
TCTACATCCTGTGCTGAGAGCCAGCTCTTCCACGCCCATAGAGGGGAGTCCCATGACC
CTGACCTGTGAGACCCAGCTCTCTCCACAGAGGCCAGATGTCCAGCTGCAATTCTCCC
TCTTCAGAGATAGCCAGACCCTCGGATTGGGCTGGAGTAGGTCCCCCAGACTCCAGAT
CCCTGCCATGTGGACTGAAGACTCAGGGTCTTACTGGTGTGAGGTGGAGACAGTGACT
CACAGCATCAAAAAAAGGAGCCTGAGATCTCAGATACGTGTACAGAGAGTCCCTGTGT
CTAATGTGAATCTAGAGATCCGGCCCACCGGAGGGCAGCTGATTGAAGGAGAAAATAT
GGTCCTTATTTGCTCAGTAGCCCAGGGTTCAGGGACTGTCACATTCTCCTGGCACAAA
GAAGGAAGAGTAAGAAGCCTGGGTAGAAAGACCCAGCGTTCCCTGTTGGCAGAGCTGC
ATGTTCTCACCGTGAAGGAGAGTGATGCAGGGAGATACTACTGTGCAGCTGATAACGT
TCACAGCCCCATCCTCAGCACGTGGATTCGAGTCACCGTGAGAATTCCGGTATCTCAC
CCTGTCCTCACCTTCAGGGCTCCCAGGGCCCACACTGTGGTGGGGGACCTGCTGGAGC
TTCACTGTGAGTCCCTGAGAGGCTCTCCCCCGATCCTGTACCGATTTTATCATGAGGA
TGTCACCCTGGGGAACAGCTCAGCCCCCTCTGGAGGAGGAGCCTCCTTCAACCTCTCT
CTGACTGCAGAACATTCTGGAAACTACTCATGTGAGGCTCTCGAG ORF Start: at 1 ORF
Stop: end of sequence SEQ ID NO: 96 421 aa MW at 47243.1kD NOV17b,
KLGEKVALICSSISHSLAQGDTYWYHDEKLLKIKHDKIQITEPGNYQCKTRGSSLSDA
207775340
VHVEFSPDWLILQALHPVFEGDNVILRCQGKDNKNTHQKVYYKDGKQLPNSYNLEKIT Protein
VNSVSRDNSKYHCTAYRKFYILDIEVTSKPLNIQVQELFLHPVLRASSSTPIEGSFMT Sequence
LTCETQLSPQRPDVQLQFSLFRDSQTLGLGWSRSPRLQIPANWTEDSGSYWCEVETVT
HSIKKRSLRSQIRVQRVPVSNVNLEIRPTGGQLIEGENMVLICSVAQGSGTVTFSWHK
EGRVRSLGRKTQRSLLAELHVLTVKESDAGRYYCAADNVHSPILSTWIRVTVRIPVSH
PVLTFRAPRAHTVVGDLLELHCESLRGSPPILYRFYHEDVTLGNSSAPSGGGASFNLS
LTAEHSGNYSCEALE SEQ ID NO: 97 1263 bp NOV17c,
AAGCTTGGAGAAAAAGTGGCTCTCATATGCAGCAGCATATCACATTCCCTAGCCCAGG
207775361
GAGACACATATTGGTATCACGATGAGAAGTTGTTGAAAATAAAACATGACAAGATCCA DNA
AATTACAGAGCCTGGAAATTACCAATGTAAGACCCGAGGATCCTCCCTCAGTGATGCC Sequence
GTGCATGTGGAATTTTCACCTGACTGGCTGATCCTGCAGGCTTTACATCCTGTCTTTG
AAGGAGACAATGTCATTCTGAGATGTCAGGGGAAAGACAACAAAAACACTCATCAAAA
GGTTTACTACAAGGATGGAAAACAGCTTCCTAATAGTTATAATTTAGAGAAGATCACA
GTGAATTCAGTCTCCAGGGATAATAGCAAATATCATTGTACTGCTTATAGGAAGTTTT
ACATACTTGACATTGAAGTAACTTCAAAACCCCTAAATATCCAAGTTCAAGAGCTGTT
TCTACATCCTGTGCTGAGAGCCAGCTCTTCCACGCCCATAGAGGGGAGTCCCATGACC
CTGACCTGTGAGACCCAGCTCTCTCCACAGAGGCCAGATGTCCAGCTGCAATTCTCCC
TCTTCAGAGATAGCCAGACCCTCGGATTGGGCTGGAGCAGGTCCCCCAGACTCCAGAT
CCCTGCCATGTGGACTGAAGACTCAGGGTCTTACTGGTGTGAGGTGGAGACAGTGACT
CACAGCATCAAAAAAAGGAGCCTGAGATCTCAGATACGTGTACAGAGAGTCCCTGTGT
CTAATGTGAATCTAGAGATCCGGCCCACCGGAGGGCAGCTGATTGAAGGAGAAAATAT
GGTCCTTATTTGCTCAGTAGCCCAGGGTTCAGGGACTGTCACATTCTCCTGGCACAAA
GAAGGAAGAGTAAGAAGCCTGGGTAGAAAGACCCAGCGTTCCCTGTTGGCAGAGCTGC
ATGTTCTCACCGTGAAGGAGAGTGATGCAGGGAGATACTACTGTGCAGCTGATAACGT
TCACAGCCCCATCCTCAGCACGTGGATTCGAGTCACCGTGAGAATTCCGGTATCTCAC
CCTGTCCTCACCTTCAGGGCTCCCAGGGCCCACACTGTGGTGGGGGACCTGCTGGAGC
TTCACTGTGAGTCCCTGAGAGGCTCTCCCCCGATCCTGTACCGATTTTATCATGAGGA
TGTCACCCTGGGGAACAGCTCAGCCCCCTCTGGAGGAGGAGCCTCCTTCAACCTCTCT
CTGACTGCAGAACATTCTGGAAACTACTCATGTGAGGCTCTCGAG ORF Start: at 1 ORF
Stop: end of sequence SEQ ID NO: 98 421 aa MW at 47243.1kD NOV17c,
KLGEKVALICSSISHSLAQGDTYWYHDEKLLKIKHDKIQITEFGNYQCKTRGSSLSDA
207775361
VHVEFSPDWLILQALHPVFEGDNVILRCQGKDNKNTHQKVYYKDGKQLPNSYNLEKIT Protein
VNSVSRDNSKYHCTAYRKFYILDIEVTSKPLNIQVQELFLHPVLRASSSTPIEGSPMT Sequence
LTCETQLSPQRPDVQLQFSLFRDSQTLGLGWSRSPRLQIPAMWTEDSGSYWCEVETVT
HSIKKRSLRSQIRVQRVPVSNVNLEIRPTGGQLIEGENMVLICSVAQGSGTVTFSWHK
EGRVRSLGRKTQRSLLAELHVLTVKESDAGRYYCAADNVHSPILSTWIRVTVRIPVSH
PVLTFRAPRAHTVVGDLLELHCESLRGSPPILYRFYHEDVTLGNSSAPSGGGASFNLS
LTAEHSGNYSCEALE SEQ ID NO: 99 1263bp NOV17d,
AAGCTTGGAGAAAAAGTGGCTCTCATATGCAGCAGCATATCACATTCCCTAGCCCAGG
207775365
GAGACACATATTGGTATCACGATGAGAAGTTGTTGAAAATAAAACATGACAAGATCCA DNA
AATTACAGAGCCTGGAAATTACCAATGTAAGACCCGAGGATCCTCCCTCAGTGATGCC Sequence
GTGCATGTGGAATTTTCACCTGACTGGCTGATCCTGCAGGCTTTACATCCTGTCTTTG
AAGGAGACAATGTCATTCTGAGATGTCAGGGGAAAGACAACAAAAACACTCATCAAAA
GGTTTACTACAAGGATGGAAAACAGCTTCCTAATAGTTATAATTTAGAGAAGATCACA
GTGAATTCAGTCTCCAGGGATAATAGCAAATATCATTGTACTGCTTATAGGAAGTTTT
ACATACTTGACATTGAAGTAACTTCAAAACCCCTAAATATCCAAGTTCAGGAGCTGTT
TCTACATCCTGTGCTGAGAGCCAGCTCTTCCACGCCCATAGAGGGGAGTCCCATGACC
CTGACCTGTGAGACCCAGCTCTCTCCACAGAGGCCAGATGTCCAGCTGCAATTCTCCC
TCTTCAGAGATAGCCAGACCCCCGGATTGGGCTGGAGCAGGTCCCCCAGACTCCAGAT
CCCTGCCATGTGGACTGAAGACTCAGGGTCTTACTGGTGTGAGGTGGAGACAGTGACT
CACAGCATCAAAAAAAGGAGCCTGAGATCTCAGATACGTGTACAGAGAGTCCCTGTGT
CTAATGTGAATCTAGAGATCCGGCCCACCGGAGGGCAGCTGATTGAAGGAGAAAATAT
GGTCCTTATTTGCTCAGTAGCCCAGGGTTCAGGGACTGTCACATTCTCCTGGCACAAA
GAAGGAAGAGTAAGAAGCCTGGGTAGAAAGACCCAGCGTTCCCTGTTGGCAGAGCTGC
ATGTTCTCACCGTGAAGGAGAGTGATGCAGGGAGATACTACTGTGCAGCTGATAACGT
TCACAGCCCCATCCTCAGCACGTGGATTCGAGTCACCGTGAGAATTCCGGTATCTCAC
CCTGTCCCCACCTTCAGGGCTCCCAGGGCCCACACTGTGGTGGGGGACCTGCTGGAGC
TTCACTGTGAGTCCCTGAGAGGCTCTCCCCCGATCCTGTACCGATTTTATCATGAGGA
TGTCACCCTGGGGAACAGCTCAGCCCCCTCTGGAGGAGGAGACTCCTTCAACCTCTCT
CTGACTGCAGAACATTCTGGAAACTACTCATGTGAGGCTCTCGAG ORF Start: at 1 ORF
Stop: end of sequence SEQ ID NO: 100 421 aa MW at 47255.0kD NOV17d,
KLGEKVALICSSISHSLAQGDTYWYHDEKLLKIKHDKIQITEPGNYQCKTRGSSLSDA
207775365
VHVEFSPDWLILQALHPVFEGDNVILRCQGKDNKNTHQKVYYKDGKQLPNSYNLEKIT Protein
VNSVSRDNSKYHCTAYRKFYILDIEVTSKPLNIQVQELFLHPVLRASSSTPIEGSPMT Sequence
LTCETQLSPQRPDVQLQFSLFRDSQTPGLGWSRSPRLQIPAMWTEDSGSYWCEVETVT
HSIKKRSLRSQIRVQRVPVSNVNLEIRPTGGQLIEGENMVLICSVAQGSGTVTFSWHK
EGRVRSLGRKTQRSLLAELHVLTVKESDAGRYYCAADNVHSPILSTWIRVTVRIPVSH
PVPTFRAPRAHTVVGDLLELHCESLRGSPPILYRFYHEDVTLGNSSAPSGGGDSFNLS
LTAEHSGNYSCEALE
[0407] Sequence comparison of the above protein sequences yields
the following sequence relationships shown in Table 17B.
TABLE-US-00090 TABLE 17B Comparison of NOV17a against NOV17b
through NOV17d. NOV17a Residues/ Identities/Similarities for the
Protein Sequence Match Residues Matched Region NOV17b 37 . . . 453
404/417 (96%) 3 . . . 419 405/417 (96%) NOV17c 37 . . . 453 404/417
(96%) 3 . . . 419 405/417 (96%) NOV17d 37 . . . 453 413/417 (99%) 3
. . . 419 414/417 (99%)
[0408] Further analysis of the NOV17a protein yielded the following
properties shown in Table 17C. TABLE-US-00091 TABLE 17C Protein
Sequence Properties NOV17a PSort 0.5374 probability located in
outside; 0.1900 probability analysis: located in lysosome (lumen);
0.1000 probability located in endoplasmic reticulum (membrane);
0.1000 probability located in endoplasmic reticulum (lumen) SignalP
Cleavage site between residues 18 and 19 analysis:
[0409] A search of the NOV17a protein against the Geneseq database,
a proprietary database that contains sequences published in patents
and patent publication, yielded several homologous proteins shown
in Table 17D. TABLE-US-00092 TABLE 17D Geneseq Results for NOV17a
NOV17a Identities/ Residues/ Similarities for Geneseq
Protein/Organism/Length Match the Matched Expect Identifier [Patent
#, Date] Residues Region Value AAB82316 Human immunoglobulin
receptor 1 . . . 564 564/564 (100%) 0.0 IRTA3 protein - Homo
sapiens, 1 . . . 564 564/564 (100%) 734 aa. [WO200138490-A2, 31-
MAY-2001] AAB82314 Human immunoglobulin receptor 1 . . . 564
259/568 (45%) e-130 isoform IRTA2b - Homo sapiens, 1 . . . 561
334/568 (58%) 592 aa. [WO200138490-A2, 31- MAY-2001] AAB82315 Human
immunoglobulin receptor 1 . . . 575 261/579 (45%) e-129 isoform
IRTA2c - Homo sapiens, 1 . . . 572 338/579 (58%) 977 aa.
[WO200138490-A2, 31- MAY-2001] AAB82313 Human immunoglobulin
receptor 1 . . . 575 261/579 (45%) e-129 isoform IRTA2a - Homo
sapiens, 1 . . . 572 338/579 (58%) 759 aa. [WO200138490-A2, 31-
MAY-2001] AAB82317 Human immunoglobulin receptor 100 . . . 472
227/374 (60%) e-129 IRTA4 protein - Homo sapiens, 18 . . . 389
280/374 (74%) 508 aa. [WO200138490-A2, 31- MAY-2001]
[0410] In a BLAST search of public sequence datbases, the NOV17a
protein was found to have homology to the proteins shown in the
BLASTP data in Table 17E. TABLE-US-00093 TABLE 17E Public BLASTP
Results for NOV17a NOV17a Identities/ Protein Residues/
Similarities for Accession Match the Matched Expect Number
Protein/Organism/Length Residues Portion Value Q96LA4 FC
RECEPTOR-LIKE PROTEIN 1 . . . 564 564/564 (100%) 0.0 3 - Homo
sapiens (Human), 734 aa. 1 . . . 564 564/564 (100%) Q96P31 SH2
DOMAlN-CONTAINING 1 . . . 564 564/564 (100%) 0.0 PHOSPHATASE ANCHOR
1 . . . 564 564/564 (100%) PROTEIN 2A - Homo sapiens (Human), 734
aa. Q96P29 SH2 DOMAIN-CONTAINING 1 . . . 564 563/570 (98%) 0.0
PHOSPHATASE ANCHOR 1 . . . 570 564/570 (98%) PROTEIN 2C - Homo
sapiens (Human), 740 aa. CAC05323 BA367J7.2.1 (NOVEL 1 . . . 548
548/548 (100%) 0.0 IMMUNOGLOBULIN DOMAINS 1 . . . 548 548/548
(100%) CONTAINING PROTEIN (ISOFORM 1)) - Homo sapiens (Human), 548
aa (fragment). Q96P30 SH2 DOMAlN-CONTAINING 111 . . . 564 318/457
(69%) e-167 PHOSPHATASE ANCHOR 35 . . . 469 347/457 (75%) PROTEIN
2B - Homo sapiens (Human), 639 aa.
[0411] PFam analysis predicts that the NOV17a protein contains the
domains shown in the Table 17F. TABLE-US-00094 TABLE 17F Domain
Analysis of NOV17a NOV17a Identities/ Match Similarities Pfam
Domain Region for the Matched Region Expect Value ig 37 . . . 84
12/52 (23%) 0.84 29/52 (56%) ig 113 . . . 165 12/57 (21%) 0.52
38/57 (67%) ig 204 . . . 262 18/61 (30%) 2.3e-08 43/61 (70%) ig 302
. . . 360 15/61 (25%) 8.2e-10 46/61 (75%) ig 397 . . . 453 13/59
(22%) 0.0004 45/59 (76%) ig 490 . . . 546 13/60 (22%) 1.7e-05 43/60
(72%)
Example 18
[0412] The NOV18 clone was analyzed, and the nucleotide and encoded
polypeptide sequences are shown in Table 18A. TABLE-US-00095 TABLE
18A NOV18 Sequence Analysis SEQ ID NO: 101 360 bp NOV18a
CGCTGCTCCTGCTGCTGCTGGCGCTGTACACCGCGCGTGTGGACGGGTCCAAATGCAA
CG50213-01
GTGCTCCCGGAAGGGACCCAAGATCCGCTACAGCGACGTGAAGAAGCTGGAAATGAAG DNA
CCAAAGTACCCGCACTGCGAGGAGAAGATGGTTATCATCACCACCAAGAGCGTGTCCA Sequence
GGTACCGAGGTCAGGAGCACTGCCTGCACCCCAAGCTGCAGAGCACCAAGCGCTTCAT
CAAGTGGTACAACGCCTGGAACGAGAAGCGCAGGGTCTACGAAGAATAGGGTGAAAAA
CCTCAGAAGGGAAAACTCCAAACCAGTTGGGAGACTTGTGCAAAGGACTTTGCAGATT
AAAAAAAAAAAA ORF Start: at 3 ORF Stop: TAG at 279 SEQ ID NO: 102 92
aa MW at 11045.0kD NOV18a,
LLLLLLALYTARVDGSKCKCSRKGPKIRYSDVKKLEMKPKYPHCEEKMVIITTKSVSR
CG50213-01 YRGQEHCLHPKLQSTKRFIKWYNAWNEKRRVYEE Protein Sequence SEQ
ID NO: 103 228 bp NOV18b,
AAATGCAAGTGCTCCCGGAAGGGACCCAAGATCCGCTACAGCGACGTGAAGAAGCTGG
CG50213-02
AAATGAAGCCAAAGTACCCGCACTGCGAGGAGAAGATGGTTATCATCACCACCAAGAG DNA
CGTGTCCAGGTACCGAGGTCAGGAGCACTGCCTGCACCCCAAGCTGCAGAGCACCAAG Sequence
CGCTTCATCAAGTGGTACAACGCCTGGAACGAGAAGCGCAGGGTCTACGAAGAA ORF Start:
at 1 ORF Stop: end of sequence SEQ ID NO: 104 76 aa MW at 9331.9kD
NOV18b, KCKCSRKGPKIRYSDVKKLEMKPKYPHCEEKMVIITTKSVSRYRGQEHCLHPKLQSTK
CG50213-02 RFIKWYNAWNEKRRVYEE Protein Sequence SEQ ID NO: 105 228
bp NOV18c,
AAATGCAAGTGCTCCCGGAAGGGACCCAAGATCCGCTACAGCGACGTGAAGAAGCTGG
CG50213-03
AAATGAAGCCAAAGTACCCGCACTGCGAGGAGAAGATGGTTATCATCACCACCAAGAG DNA
CGTGTCCAGGTACCGAGGTCAGGAGCACTGCCTGCACCCCAAGCTGCAGAGCACCAAG Sequence
CGCTTCATCAAGTGGTACAACGCCTGGAACGAGAAGCGCAGGGTCTACGAAGAA ORF Start:
at 1 ORF Stop: end of sequence SEQ ID NO: 106 76 aa MW at 9331.9kD
NOV18c, KCKCSRKGPKIRYSDVKKLEMKPKYPHCEEKMVIITTKSVSRYRGQEHCLHPKLQSTK
CG50213-03 RFIKWYNAWNEKRRVYEE Protein Sequence
[0413] Sequence comparison of the above protein sequences yields
the following sequence relationships shown in Table 18B.
TABLE-US-00096 TABLE 18B Comparison of NOV18a against NOV18b and
NOV18c. NOV18a Residues/ Identities/ Similarities for the Protein
Sequence Match Residues Matched Region NOV18b 17 . . . 92 76/76
(100%) 1 . . . 76 76/76 (100%) NOV18c 17 . . . 92 76/76 (100%) 1 .
. . 76 76/76 (100%)
[0414] Further analysis of the NOV18a protein yielded the following
properties shown in Table 18C. TABLE-US-00097 TABLE 18C Protein
Sequence Properties NOV18a PSort 0.3700 probability located in
outside; 0.1800 probability analysis: located in nucleus; 0.1000
probability located in endoplasmic reticulum (membrane); 0.1000
probability located in endoplasmic reticulum (lumen) SignalP
Cleavage site between residues 16 and 17 analysis:
[0415] A search of the NOV18a protein against the Geneseq database,
a proprietary database that contains sequences published in patents
and patent publication, yielded several homologous proteins shown
in Table 18D. TABLE-US-00098 TABLE 18D Geneseq Results for NOV18a
NOV18a Identities/ Residues/ Similarities for Geneseq
Protein/Organism/Length [Patent Match the Matched Expect Identifier
#, Date] Residues Region Value ABB72228 Human protein isolated from
skin 1 . . . 92 92/92 (100%) 1e-50 cells SEQ ID NO: 344 - Homo 4 .
. . 95 92/92 (100%) sapiens, 95 aa. [WO200190357-A1, 29-NOV-2001]
AAB56028 Skin cell protein, SEQ ID NO: 344 - 1 . . . 92 92/92
(100%) 1e-50 Homo sapiens, 95 aa. 4 . . . 95 92/92 (100%)
[WO200069884-A2, 23-NOV-2000] AAB88478 Human membrane or secretory
1 . . . 92 92/92 (100%) 1e-50 protein clone PSEC0212 - Homo 20 . .
. 111 92/92 (100%) sapiens, 111 aa. [EP1067182-A2, 10-JAN-2001]
AAE05371 Human huKS1 protein - Homo 1 . . . 92 92/92 (100%) 1e-50
sapiens, 95 aa. [WO200148192-A1, 4 . . . 95 92/92 (100%)
05-JUL-2001] AAY76089 Human CXC chemokine homologue 1 . . . 92
92/92 (100%) 1e-50 huKS1, SEQ ID NO: 344 - Homo 4 . . . 95 92/92
(100%) sapiens, 95 aa. [WO9955865-A1, 04-NOV-1999]
[0416] In a BLAST search of public sequence datbases, the NOV18a
protein was found to have homology to the proteins shown in the
BLASTP data in Table 18E. TABLE-US-00099 TABLE 18E Public BLASTP
Results for NOV18a NOV18a Identities/ Protein Residues/
Similarities for Accession Match the Matched Expect Number
Protein/Organism/Length Residues Portion Value JG0182 chemokine
BRAK - human, 99 aa. 1 . . . 92 92/92 (100%) 2e-50 8 . . . 99 92/92
(100%) Q9BTR1 SMALL INDUCIBLE CYTOKINE 1 . . . 92 92/92 (100%)
2e-50 SUBFAMILY B (CYS-X-CYS), 20 . . . 111 92/92 (100%) MEMBER 14
(BRAK) - Homo sapiens (Human), 111 aa. O95715 Small inducible
cytokine B14 1 . . . 92 92/92 (100%) 2e-50 precursor (Chemokine
BRAK) - 8 . . . 99 92/92 (100%) Homo sapiens (Human), 99 aa. Q9NS21
CHEMOKINE MIP-2 GAMMA - 1 . . . 92 91/92 (98%) 9e-50 Homo sapiens
(Human), 111 aa. 20 . . . 111 91/92 (98%) Q91V02 MIP2GAMMA - Mus
musculus 1 . . . 92 87/92 (94%) 7e-48 (Mouse), 95 aa (fragment). 4
. . . 95 90/92 (97%)
[0417] PFam analysis predicts that the NOV18a protein contains the
domains shown in the Table 18F. TABLE-US-00100 TABLE 18F Domain
Analysis of NOV18a Identities/ NOV18a Similarities for Pfam Domain
Match Region the Matched Region Expect Value
Example 19
[0418] The NOV19 clone was analyzed, and the nucleotide and encoded
polypeptide sequences are shown in Table 19A. TABLE-US-00101 TABLE
19A NOV19 Sequence Analysis SEQ ID NO: 107 619 bp NOV19a,
GCTGCCTGCCTCCTCATGTTCCCCTCCACCACAGCGGACTGCCTGTCGCGGTGCTCCT
CG88912-02
TGTGTGCTGTAAAGACCCAGGATGGTCCCAAACCTATCAATCCCCTGATTTGCTCCCT DNA
GCAATGCCAGGCTGCCCTGCTGCCCTCTGAGGAATGGGAGAGATGCCAGAGCTTTCTG Sequence
TCTTTTTTCACCCCCTCCACCCTTGGGCTCAATGACAAGGAGGACTTGGGGAGCAAGT
CGGTTGGGGAAGGGCCCTACAGTGAGCTGGCCAAGCTCTCTGGGTCATTCCTGAAGGA
GCTGAACGATGGTGCCATGGAGACTGGCACACTCTATCTCGCTGAGGAGGACCCCAAG
GAGCAGGTCAAACGCTATGGGGGCTTTTTGCGCAAATACCCCAAGAGGAGCTCAGAGG
TGGCTGGGGAGGGGGACGGGGATAGCATGGGCCATGAGGACCTGTACAAACGCTATGG
GGGCTTCTTGCGGCGCATTCGTCCCAAGCTCAAGTGGGACAACCAGAAGCGCTATGGC
GGTTTTCTCCGGCGCCAGTTCAAGGTGGTGACTCGGTCTCAGGAAGATCCGAATGCTT
ACTCTGGAGAGCTTTTTGATGCATAAGCACTTCTTTTCA ORF Start: at 1 ORF Stop:
TAA at 604 SEQ ID NO: 108 201 aa MW at 22447.1kD NOV19a,
AACLLMFPSTTADCLSRCSLCAVKTQDGPKFINPLICSLQCQAALLPSEEWERCQSFL
CG88912-02
SFFTPSTLGLNDKEDLGSKSVGEGPYSELAKLSGSFLKELNDGAMETGTLYLAEEDPK Protein
EQVKRYGGFLRKYPKRSSEVAGEGDGDSMGHEDLYKRYGGFLRRIRPKLKWDNQKRYG Sequence
GFLRRQFKVVTRSQEDPNAYSGELFDA
[0419] Further analysis of the NOV19a protein yielded the following
properties shown in Table 19B. TABLE-US-00102 TABLE 19B Protein
Sequence Properties NOV19a PSort 0.7562 probability located in
mitochondrial matrix space; analysis: 0.4352 probability located in
mitochondrial inner membrane; 0.4352 probability located in
mitochondrial intermembrane space; 0.4352 probability located in
mitochondrial outer membrane SignalP Cleavage site between residues
13 and 14 analysis:
[0420] A search of the NOV19a protein against the Geneseq database,
a proprietary database that contains sequences published in patents
and patent publication, yielded several homologous proteins shown
in Table 19C. TABLE-US-00103 TABLE 19C Geneseq Results for NOV19qa
NOV19a Identities/ Residues/ Similarities for Geneseq
Protein/Organism/Length [Patent Match the Matched Expect Identifier
#, Date] Residues Region Value AAM79544 Human protein SEQ ID NO
3190 - 1 . . . 201 201/246 (81%) e-110 Homo sapiens, 256 aa. 11 . .
. 256 201/246 (81%) [WO200157190-A2, 09-AUG- 2001] AAM78560 Human
protein SEQ ID NO 1222 - 1 . . . 201 201/246 (81%) e-110 Homo
sapiens, 254 aa. 9 . . . 254 201/246 (81%) [WO200157190-A2, 09-AUG-
2001] AAM05438 Peptide #4120 encoded by probe 135 . . . 201 67/67
(100%) 2e-34 for measuring breast gene 1 . . . 67 67/67 (100%)
expression - Homo sapiens, 67 aa. [WO200157270-A2, 09-AUG- 2001]
AAM30301 Peptide #4338 encoded by probe 135 . . . 201 67/67 (100%)
2e-34 for measuring placental gene 1 . . . 67 67/67 (100%)
expression - Homo sapiens, 67 aa. [WO200157272-A2, 09-AUG- 2001]
AAM17791 Peptide #4225 encoded by probe 135 . . . 201 67/67 (100%)
2e-34 for measuring cervical gene 1 . . . 67 67/67 (100%)
expression - Homo sapiens, 67 aa. [WO200157278-A2, 09-AUG-
2001]
[0421] In a BLAST search of public sequence datbases, the NOV19a
protein was found to have homology to the proteins shown in the
BLASTP data in Table 19D. TABLE-US-00104 TABLE 19D Public BLASTP
Results for NOV19a NOV19a Identities/ Protein Residues/
Similarities for Accession Match the Matched Expect Number
Protein/Organism/Length Residues Portion Value P01213
Beta-neoendorphin-dynorphin 1 . . . 201 201/246 (81%) e-110
precursor (Proenkephalin B) 9 . . . 254 201/246 (81%)
(Preprodynorphin) [Contains: Beta- neoendorphin; Dynorphin; Leu-
Enkephalin; Rimorphin; Leumorphin] - Homo sapiens (Human), 254 aa.
P01214 Beta-neoendorphin-dynorphin 1 . . . 200 164/247 (66%) 2e-84
precursor (Proenkephalin B) 9 . . . 255 171/247 (68%)
(Preprodynorphin) [Contains: Beta- neoendorphin; Dynorphin; Leu-
Enkephalin; Rimorphin; Leumorphin] - Sus scrofa (Pig), 256 aa.
Q95104 Beta-neoendorphin-dynorphin 1 . . . 200 155/249 (62%) 7e-79
precursor (Proenkephalin B) 9 . . . 257 170/249 (68%)
(Preprodynorphin) [Contains: Beta- neoendorphin; Dynorphin; Leu-
Enkephalin; Rimorphin; Leumorphin] - Bos taurus (Bovine), 258 aa.
Q60478 Beta-neoendorphin-dynorphin 1 . . . 200 153/238 (64%) 3e-77
precursor (Proenkephalin B) 9 . . . 244 165/238 (69%)
(Preprodynorphin) [Contains: Beta- neoendorphin; Dynorphin; Leu-
Enkephalin; Rimorphin; Leumorphin] - Cavia porcellus (Guinea pig),
245 aa. O35852 PREPRODYNORPHIN - Mus 1 . . . 198 140/238 (58%)
4e-69 musculus (Mouse), 248 aa 9 . . . 246 157/238 (65%)
(fragment).
[0422] PFam analysis predicts that the NOV19a protein contains the
domains shown in the Table 19E. TABLE-US-00105 TABLE 19E Domain
Analysis of NOV19a Identities/ NOV19a Similarities for the Pfam
Domain Match Region Matched Region Expect Value Opiods_neuropep 1 .
. . 201 145/267 (54%) 1.3e-115 197/267 (74%)
Example B
Sequencing Methodology and Identification of NOVX Clones
[0423] 1. GeneCalling.TM. Technology: This is a proprietary method
of performing differential gene expression profiling between two or
more samples developed at CuraGen and described by Shimkets, et
al., "Gene expression analysis by transcript profiling coupled to a
gene database query" Nature Biotechnology 17:198-803 (1999). cDNA
was derived from various human samples representing multiple tissue
types, normal and diseased states, physiological states, and
developmental states from different donors. Samples were obtained
as whole tissue, primary cells or tissue cultured primary cells or
cell lines. Cells and cell lines may have been treated with
biological or chemical agents that regulate gene expression, for
example, growth factors, chemokines or steroids. The cDNA thus
derived was then digested with up to as many as 120 pairs of
restriction enzymes and pairs of linker-adaptors specific for each
pair of restriction enzymes were ligated to the appropriate end.
The restriction digestion generates a mixture of unique cDNA gene
fragments. Limited PCR amplification is performed with primers
homologous to the linker adapter sequence where one primer is
biotinylated and the other is fluorescently labeled. The doubly
labeled material is isolated and the fluorescently labeled single
strand is resolved by capillary gel electrophoresis. A computer
algorithm compares the electropherograms from an experimental and
control group for each of the restriction digestions. This and
additional sequence-derived information is used to predict the
identity of each differentially expressed gene fragment using a
variety of genetic databases. The identity of the gene fragment is
confirmed by additional, gene-specific competitive PCR or by
isolation and sequencing of the gene fragment.
[0424] 2. SeqCalling.TM. Technology: cDNA was derived from various
human samples representing multiple tissue types, normal and
diseased states, physiological states, and developmental states
from different donors. Samples were obtained as whole tissue,
primary cells or tissue cultured primary cells or cell lines. Cells
and cell lines may have been treated with biological or chemical
agents that regulate gene expression, for example, growth factors,
chemokines or steroids. The cDNA thus derived was then sequenced
using CuraGen's proprietary SeqCalling technology. Sequence traces
were evaluated manually and edited for corrections if appropriate.
cDNA sequences from all samples were assembled together, sometimes
including public human sequences, using bioinformatic programs to
produce a consensus sequence for each assembly. Each assembly is
included in CuraGen Corporation's database. Sequences were included
as components for assembly when the extent of identity with another
component was at least 95% over 50 bp. Each assembly represents a
gene or portion thereof and includes information on variants, such
as splice forms single nucleotide polymorphisms (SNPs), insertions,
deletions and other sequence variations.
3. PathCalling.TM. Technology:
[0425] The NOVX nucleic acid sequences are derived by laboratory
screening of cDNA library by the two-hybrid approach. cDNA
fragments covering either the full length of the DNA sequence, or
part of the sequence, or both, are sequenced. In silico prediction
was based on sequences available in CuraGen Corporation's
proprietary sequence databases or in the public human sequence
databases, and provided either the full length DNA sequence, or
some portion thereof.
[0426] The laboratory screening was performed using the methods
summarized below:
[0427] cDNA libraries were derived from various human samples
representing multiple tissue types, normal and diseased states,
physiological states, and developmental states from different
donors. Samples were obtained as whole tissue, primary cells or
tissue cultured primary cells or cell lines. Cells and cell lines
may have been treated with biological or chemical agents that
regulate gene expression, for example, growth factors, chemokines
or steroids. The cDNA thus derived was then directionally cloned
into the appropriate two-hybrid vector (Gal4-activation domain
(Gal4-AD) fusion). Such cDNA libraries as well as commercially
available cDNA libraries from Clontech (Palo Alto, Calif.) were
then transferred from E. coli into a CuraGen Corporation
proprietary yeast strain (disclosed in U.S. Pat. Nos. 6,057,101 and
6,083,693, incorporated herein by reference in their
entireties).
[0428] Gal4-binding domain (Gal4-BD) fusions of a CuraGen
Corportion proprietary library of human sequences was used to
screen multiple Gal4-AD fusion cDNA libraries resulting in the
selection of yeast hybrid diploids in each of which the Gal4-AD
fusion contains an individual cDNA. Each sample was amplified using
the polymerase chain reaction (PCR) using non-specific primers at
the cDNA insert boundaries. Such PCR product was sequenced;
sequence traces were evaluated manually and edited for corrections
if appropriate. cDNA sequences from all samples were assembled
together, sometimes including public human sequences, using
bioinformatic programs to produce a consensus sequence for each
assembly. Each assembly is included in CuraGen Corporation's
database. Sequences were included as components for assembly when
the extent of identity with another component was at least 95% over
50 bp. Each assembly represents a gene or portion thereof and
includes information on variants, such as splice forms single
nucleotide polymorphisms (SNPs), insertions, deletions and other
sequence variations.
[0429] Physical clone: the cDNA fragment derived by the screening
procedure, covering the entire open reading frame is, as a
recombinant DNA, cloned into pACT2 plasmid (Clontech) used to make
the cDNA library. The recombinant plasmid is inserted into the host
and selected by the yeast hybrid diploid generated during the
screening procedure by the mating of both CuraGen Corporation
proprietary yeast strains N.sub.1O.sub.6' and YULH (U.S. Pat. Nos.
6,057,101 and 6,083,693).
[0430] 4. RACE: Techniques based on the polymerase chain reaction
such as rapid amplification of cDNA ends (RACE), were used to
isolate or complete the predicted sequence of the cDNA of the
invention. Usually multiple clones were sequenced from one or more
human samples to derive the sequences for fragments. Various human
tissue samples from different donors were used for the RACE
reaction. The sequences derived from these procedures were included
in the SeqCalling Assembly process described in preceding
paragraphs.
[0431] 5. Exon Linking: The NOVX target sequences identified in the
present invention were subjected to the exon linking process to
confirm the sequence. PCR primers were designed by starting at the
most upstream sequence available, for the forward primer, and at
the most downstream sequence available for the reverse primer. In
each case, the sequence was examined, walking inward from the
respective termini toward the coding sequence, until a suitable
sequence that is either unique or highly selective was encountered,
or, in the case of the reverse primer, until the stop codon was
reached. Such primers were designed based on in silico predictions
for the full length cDNA, part (one or more exons) of the DNA or
protein sequence of the target sequence, or by translated homology
of the predicted exons to closely related human sequences from
other species. These primers were then employed in PCR
amplification based on the following pool of human cDNAs: adrenal
gland, bone marrow, brain--amygdala, brain--cerebellum,
brain--hippocampus, brain--substantia nigra, brain--thalamus,
brain--whole, fetal brain, fetal kidney, fetal liver, fetal lung,
heart, kidney, lymphoma--Raji, mammary gland, pancreas, pituitary
gland, placenta, prostate, salivary gland, skeletal muscle, small
intestine, spinal cord, spleen, stomach, testis, thyroid, trachea,
uterus. Usually the resulting amplicons were gel purified, cloned
and sequenced to high redundancy. The PCR product derived from exon
linking was cloned into the pCR2.1 vector from Invitrogen. The
resulting bacterial clone has an insert covering the entire open
reading frame cloned into the pCR2.1 vector. The resulting
sequences from all clones were assembled with themselves, with
other fragments in CuraGen Corporation's database and with public
ESTs. Fragments and ESTs were included as components for an
assembly when the extent of their identity with another component
of the assembly was at least 95% over 50 bp. In addition, sequence
traces were evaluated manually and edited for corrections if
appropriate. These procedures provide the sequence reported
herein.
[0432] 6. Physical Clone: Exons were predicted by homology and the
intron/exon boundaries were determined using standard genetic
rules. Exons were further selected and refined by means of
similarity determination using multiple BLAST (for example,
tBlastN, BlastX, and BlastN) searches, and, in some instances,
GeneScan and Grail. Expressed sequences from both public and
proprietary databases were also added when available to further
define and complete the gene sequence. The DNA sequence was then
manually corrected for apparent inconsistencies thereby obtaining
the sequences encoding the full-length protein.
[0433] The PCR product derived by exon linking, covering the entire
open reading frame, was cloned into the pCR2.1 vector from
Invitrogen to provide clones used for expression and screening
purposes.
Example C
Quantitative Expression Analysis of Clones in Various Cells and
Tissues
[0434] The quantitative expression of various clones was assessed
using microtiter plates containing RNA samples from a variety of
normal and pathology-derived cells, cell lines and tissues using
real time quantitative PCR (RTQ PCR). RTQ PCR was performed on an
Applied Biosystems ABI PRISM.RTM. 7700 or an ABI PRISM.RTM. 7900 HT
Sequence Detection System. Various collections of samples are
assembled on the plates, and referred to as Panel 1 (containing
normal tissues and cancer cell lines), Panel 2 (containing samples
derived from tissues from normal and cancer sources), Panel 3
(containing cancer cell lines), Panel 4 (containing cells and cell
lines from normal tissues and cells related to inflammatory
conditions), Panel 5D/5I (containing human tissues and cell lines
with an emphasis on metabolic diseases), AI_comprehensive_panel
(containing normal tissue and samples from autoinflammatory
diseases), Panel CNSD.01 (containing samples from normal and
diseased brains) and CNS_neurodegeneration_panel (containing
samples from normal and Alzheimer's diseased brains).
[0435] RNA integrity from all samples is controlled for quality by
visual assessment of agarose gel electropherograms using 28S and
18S ribosomal RNA staining intensity ratio as a guide (2:1 to 2.5:1
28s:18s) and the absence of low molecular weight RNAs that would be
indicative of degradation products. Samples are controlled against
genomic DNA contamination by RTQ PCR reactions run in the absence
of reverse transcriptase using probe and primer sets designed to
amplify across the span of a single exon.
[0436] First, the RNA samples were normalized to reference nucleic
acids such as constitutively expressed genes (for example,
.beta.-actin and GAPDH). Normalized RNA (5 ul) was converted to
cDNA and analyzed by RTQ-PCR using One Step RT-PCR Master Mix
Reagents (Applied Biosystems; Catalog No. 4309169) and
gene-specific primers according to the manufacturer's
instructions.
[0437] In other cases, non-normalized RNA samples were converted to
single strand cDNA (sscDNA) using Superscript II (Invitrogen
Corporation; Catalog No. 18064-147) and random hexamers according
to the manufacturer's instructions. Reactions containing up to 100
.mu.g of total RNA were performed in a volume of 20 .mu.l and
incubated for 60 minutes at 42.degree. C. This reaction can be
scaled up to 50 .mu.g of total RNA in a final volume of 100 .mu.l.
sscDNA samples are then normalized to reference nucleic acids as
described previously, using 1.times. TaqMan.RTM. Universal Master
mix (Applied Biosystems; catalog No. 4324020), following the
manufacturer's instructions.
[0438] Probes and primers were designed for each assay according to
Applied Biosystems Primer Express Software package (version I for
Apple Computer's Macintosh Power PC) or a similar algorithm using
the target sequence as input. Default settings were used for
reaction conditions and the following parameters were set before
selecting primers: primer concentration=250 nM, primer melting
temperature (Tm) range=58.degree.-60.degree. C., primer optimal
Tm=59.degree. C., maximum primer difference=2.degree. C., probe
does not have 5'G, probe Tm must be 10.degree. C. greater than
primer Tm, amplicon size 75 bp to 100 bp. The probes and primers
selected (see below) were synthesized by Synthegen (Houston, Tex.,
USA). Probes were double purified by HPLC to remove uncoupled dye
and evaluated by mass spectroscopy to verify coupling of reporter
and quencher dyes to the 5' and 3' ends of the probe, respectively.
Their final concentrations were: forward and reverse primers, 900
nM each, and probe, 200 nM.
[0439] PCR conditions: When working with RNA samples, normalized
RNA from each tissue and each cell line was spotted in each well of
either a 96 well or a 384-well PCR plate (Applied Biosystems). PCR
cocktails included either a single gene specific probe and primers
set, or two multiplexed probe and primers sets (a set specific for
the target clone and another gene-specific set multiplexed with the
target probe). PCR reactions were set up using TaqMan.RTM. One-Step
RT-PCR Master Mix (Applied Biosystems, Catalog No. 4313803)
following manufacturer's instructions. Reverse transcription was
performed at 48.degree. C. for 30 minutes followed by
amplification/PCR cycles as follows: 95.degree. C. 10 min, then 40
cycles of 95.degree. C. for 15 seconds, 60.degree. C. for 1 minute.
Results were recorded as CT values (cycle at which a given sample
crosses a threshold level of fluorescence) using a log scale, with
the difference in RNA concentration between a given sample and the
sample with the lowest CT value being represented as 2 to the power
of delta CT. The percent relative expression is then obtained by
taking the reciprocal of this RNA difference and multiplying by
100.
[0440] When working with sscDNA samples, normalized sscDNA was used
as described previously for RNA samples. PCR reactions containing
one or two sets of probe and primers were set up as described
previously, using 1.times. TaqMan.RTM. Universal Master mix
(Applied Biosystems; catalog No. 4324020), following the
manufacturer's instructions. PCR amplification was performed as
follows: 95.degree. C. 10 min, then 40 cycles of 95.degree. C. for
15 seconds, 60.degree. C. for 1 minute. Results were analyzed and
processed as described previously.
[0441] Panels 1, 1.1, 1.2, and 1.3D
[0442] The plates for Panels 1, 1.1, 1.2 and 1.3D include 2 control
wells (genomic DNA control and chemistry control) and 94 wells
containing cDNA from various samples. The samples in these panels
are broken into 2 classes: samples derived from cultured cell lines
and samples derived from primary normal tissues. The cell lines are
derived from cancers of the following types: lung cancer, breast
cancer, melanoma, colon cancer, prostate cancer, CNS cancer,
squamous cell carcinoma, ovarian cancer, liver cancer, renal
cancer, gastric cancer and pancreatic cancer. Cell lines used in
these panels are widely available through the American Type Culture
Collection (ATCC), a repository for cultured cell lines, and were
cultured using the conditions recommended by the ATCC. The normal
tissues found on these panels are comprised of samples derived from
all major organ systems from single adult individuals or fetuses.
These samples are derived from the following organs: adult skeletal
muscle, fetal skeletal muscle, adult heart, fetal heart, adult
kidney, fetal kidney, adult liver, fetal liver, adult lung, fetal
lung, various regions of the brain, the spleen, bone marrow, lymph
node, pancreas, salivary gland, pituitary gland, adrenal gland,
spinal cord, thymus, stomach, small intestine, colon, bladder,
trachea, breast, ovary, uterus, placenta, prostate, testis and
adipose.
[0443] In the results for Panels 1, 1.1, 1.2 and 1.3D, the
following abbreviations are used: [0444] ca.=carcinoma, [0445]
*=established from metastasis, [0446] met=metastasis, [0447] s cell
var=small cell variant, [0448] non-s=non-sm=non-small, [0449]
squam=squamous, [0450] pl. eff=pl effusion=pleural effusion, [0451]
glio=glioma, [0452] astro=astrocytoma, and [0453]
neuro=neuroblastoma.
[0454] General_screening_panel_v1.4, v1.5 and v1.6
[0455] The plates for Panels 1.4, 1.5, and 1.6 include 2 control
wells (genomic DNA control and chemistry control) and 94 wells
containing cDNA from various samples. The samples in Panels 1.4,
1.5, and 1.6 are broken into 2 classes: samples derived from
cultured cell lines and samples derived from primary normal
tissues. The cell lines are derived from cancers of the following
types: lung cancer, breast cancer, melanoma, colon cancer, prostate
cancer, CNS cancer, squamous cell carcinoma, ovarian cancer, liver
cancer, renal cancer, gastric cancer and pancreatic cancer. Cell
lines used in Panels 1.4, 1.5, and 1.6 are widely available through
the American Type Culture Collection (ATCC), a repository for
cultured cell lines, and were cultured using the conditions
recommended by the ATCC. The normal tissues found on Panels 1.4,
1.5, and 1.6 are comprised of pools of samples derived from all
major organ systems from 2 to 5 different adult individuals or
fetuses. These samples are derived from the following organs: adult
skeletal muscle, fetal skeletal muscle, adult heart, fetal heart,
adult kidney, fetal kidney, adult liver, fetal liver, adult lung,
fetal lung, various regions of the brain, the spleen, bone marrow,
lymph node, pancreas, salivary gland, pituitary gland, adrenal
gland, spinal cord, thymus, stomach, small intestine, colon,
bladder, trachea, breast, ovary, uterus, placenta, prostate, testis
and adipose. Abbreviations are as described for Panels 1, 1.1, 1.2,
and 1.3D.
[0456] Panels 2D, 2.2, 2.3 and 2.4
[0457] The plates for Panels 2D, 2.2, 2.3 and 2.4 generally include
2 control wells and 94 test samples composed of RNA or cDNA
isolated from human tissue procured by surgeons working in close
cooperation with the National Cancer Institute's Cooperative Human
Tissue Network (CHTN) or the National Disease Research Initiative
(NDRI) or from Ardais or Clinomics). The tissues are derived from
human malignancies and in cases where indicated many malignant
tissues have "matched margins" obtained from noncancerous tissue
just adjacent to the tumor. These are termed normal adjacent
tissues and are denoted "NAT" in the results below. The tumor
tissue and the "matched margins" are evaluated by two independent
pathologists (the surgical pathologists and again by a pathologist
at NDRI/CHTN/Ardais/Clinomics). Unmatched RNA samples from tissues
without malignancy (normal tissues) were also obtained from Ardais
or Clinomics. This analysis provides a gross histopathological
assessment of tumor differentiation grade. Moreover, most samples
include the original surgical pathology report that provides
information regarding the clinical stage of the patient. These
matched margins are taken from the tissue surrounding (i.e.
immediately proximal) to the zone of surgery (designated "NAT", for
normal adjacent tissue, in Table RR). In addition, RNA and cDNA
samples were obtained from various human tissues derived from
autopsies performed on elderly people or sudden death victims
(accidents, etc.). These tissues were ascertained to be free of
disease and were purchased from various commercial sources such as
Clontech (Palo Alto, Calif.), Research Genetics, and
Invitrogen.
[0458] HASS Panel v 1.0
[0459] The HASS panel v 1.0 plates are comprised of 93 cDNA samples
and two controls. Specifically, 81 of these samples are derived
from cultured human cancer cell lines that had been subjected to
serum starvation, acidosis and anoxia for different time periods as
well as controls for these treatments, 3 samples of human primary
cells, 9 samples of malignant brain cancer (4 medulloblastomas and
5 glioblastomas) and 2 controls. The human cancer cell lines are
obtained from ATCC (American Type Culture Collection) and fall into
the following tissue groups: breast cancer, prostate cancer,
bladder carcinomas, pancreatic cancers and CNS cancer cell lines.
These cancer cells are all cultured under standard recommended
conditions. The treatments used (serum starvation, acidosis and
anoxia) have been previously published in the scientific
literature. The primary human cells were obtained from Clonetics
(Walkersville, Md.) and were grown in the media and conditions
recommended by Clonetics. The malignant brain cancer samples are
obtained as part of a collaboration (Henry Ford Cancer Center) and
are evaluated by a pathologist prior to CuraGen receiving the
samples. RNA was prepared from these samples using the standard
procedures. The genomic and chemistry control wells have been
described previously.
[0460] Panel 3D and 3.1
[0461] The plates of Panel 3D and 3.1 are comprised of 94 cDNA
samples and two control samples. Specifically, 92 of these samples
are derived from cultured human cancer cell lines, 2 samples of
human primary cerebellar tissue and 2 controls. The human cell
lines are generally obtained from ATCC (American Type Culture
Collection), NCI or the German tumor cell bank and fall into the
following tissue groups: Squamous cell carcinoma of the tongue,
breast cancer, prostate cancer, melanoma, epidermoid carcinoma,
sarcomas, bladder carcinomas, pancreatic cancers, kidney cancers,
leukemias/lymphomas, ovarian/uterine/cervical, gastric, colon, lung
and CNS cancer cell lines. In addition, there are two independent
samples of cerebellum. These cells are all cultured under standard
recommended conditions and RNA extracted using the standard
procedures. The cell lines in panel 3D, 3.1 and 1.3D are of the
most common cell lines used in the scientific literature.
[0462] Panels 4D, 4R, and 4.1D
[0463] Panel 4 includes samples on a 96 well plate (2 control
wells, 94 test samples) composed of RNA (Panel 4R) or cDNA (Panels
4D/4.1D) isolated from various human cell lines or tissues related
to inflammatory conditions. Total RNA from control normal tissues
such as colon and lung (Stratagene, La Jolla, Calif.) and thymus
and kidney (Clontech) was employed. Total RNA from liver tissue
from cirrhosis patients and kidney from lupus patients was obtained
from BioChain (Biochain Institute, Inc., Hayward, Calif.).
Intestinal tissue for RNA preparation from patients diagnosed as
having Crohn's disease and ulcerative colitis was obtained from the
National Disease Research Interchange (NDR1) (Philadelphia,
Pa.).
[0464] Astrocytes, lung fibroblasts, dermal fibroblasts, coronary
artery smooth muscle cells, small airway epithelium, bronchial
epithelium, microvascular dermal endothelial cells, microvascular
lung endothelial cells, human pulmonary aortic endothelial cells,
human umbilical vein endothelial cells were all purchased from
Clonetics (Walkersville, Md.) and grown in the media supplied for
these cell types by Clonetics. These primary cell types were
activated with various cytokines or combinations of cytokines for 6
and/or 12-14 hours, as indicated. The following cytokines were
used; IL-1 beta at approximately 1-5 ng/ml, TNF alpha at
approximately 5-10 ng/ml, IFN gamma at approximately 20-50 ng/ml,
IL-4 at approximately 5-10 ng/ml, IL-9 at approximately 5-10 ng/ml,
IL-13 at approximately 5-10 ng/ml. Endothelial cells were sometimes
starved for various times by culture in the basal media from
Clonetics with 0.1% serum.
[0465] Mononuclear cells were prepared from blood of employees at
CuraGen Corporation, using Ficoll. LAK cells were prepared from
these cells by culture in DMEM 5% FCS (Hyclone), 100 .mu.M non
essential amino acids (GibcoALife Technologies, Rockville, Md.), 1
mM sodium pyruvate (Gibco), mercaptoethanol 5.5.times.10.sup.-5M
(Gibco), and 10 mM Hepes (Gibco) and Interleukin 2 for 4-6 days.
Cells were then either activated with 10-20 ng/ml PMA and 1-2
.mu.g/ml ionomycin, IL-12 at 5-10 ng/ml, IFN gamma at 20-50 ng/ml
and IL-18 at 5-10 ng/ml for 6 hours. In some cases, mononuclear
cells were cultured for 4-5 days in DMEM 5% FCS (Hyclone), 100
.mu.M non essential amino acids (Gibco), 1 mM-sodium pyruvate
(Gibco), mercaptoethanol 5.5.times.10.sup.-5M (Gibco), and 10 mM
Hepes (Gibco) with PHA (phytohemagglutinin) or PWM (pokeweed
mitogen) at approximately 5 .mu.g/ml. Samples were taken at 24, 48
and 72 hours for RNA preparation. MLR (mixed lymphocyte reaction)
samples were obtained by taking blood from two donors, isolating
the mononuclear cells using Ficoll and mixing the isolated
mononuclear cells 1:1 at a final concentration of approximately
2.times.10.sup.6 cells/ml in DMEM 5% FCS (Hyclone), 100 .mu.M non
essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco),
mercaptoethanol (5.5.times.10.sup.5M) (Gibco), and 10 mM Hepes
(Gibco). The MLR was cultured and samples taken at various time
points ranging from 1-7 days for RNA preparation.
[0466] Monocytes were isolated from mononuclear cells using CD14
Miltenyi Beads, +ve VS selection columns and a Vario Magnet
according to the manufacturer's instructions. Monocytes were
differentiated into dendritic cells by culture in DMEM 5% fetal
calf serum (FCS) (Hyclone, Logan, Utah), 100 .mu.M non essential
amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol
5.5.times.10.sup.-5M (Gibco), and 10 mM Hepes (Gibco), 50 ng/ml
GMCSF and 5 ng/ml IL-4 for 5-7 days. Macrophages were prepared by
culture of monocytes for 5-7 days in DMEM 5% FCS (Hyclone), 100
.mu.M non essential amino acids (Gibco), 1 mM sodium pyruvate
(Gibco), mercaptoethanol 5.5.times.10.sup.-5M (Gibco), 10 mM Hepes
(Gibco) and 10% AB Human Serum or MCSF at approximately 50 ng/ml.
Monocytes, macrophages and dendritic cells were stimulated for 6
and 12-14 hours with lipopolysaccharide (LPS) at 100 ng/ml.
Dendritic cells were also stimulated with anti-CD40 monoclonal
antibody (Pharmingen) at 10 .mu.g/ml for 6 and 12-14 hours.
[0467] CD4 lymphocytes, CD8 lymphocytes and NK cells were also
isolated from mononuclear cells using CD4, CD8 and CD56 Miltenyi
beads, positive VS selection columns and a Vario Magnet according
to the manufacturer's instructions. CD45RA and CD45RO CD4
lymphocytes were isolated by depleting mononuclear cells of CD8,
CD56, CD14 and CD19 cells using CD8, CD56, CD14 and CD19 Miltenyi
beads and positive selection. CD45RO beads were then used to
isolate the CD45RO CD4 lymphocytes with the remaining cells being
CD45RA CD4 lymphocytes. CD45RA CD4, CD45RO CD4 and CD8 lymphocytes
were placed in DMEM 5% FCS (Hyclone), 100 .mu.M non essential amino
acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol
5.5.times.10.sup.-5M (Gibco), and mM Hepes (Gibco) and plated at
10.sup.6 cells/ml onto Falcon 6 well tissue culture plates that had
been coated overnight with 0.5 .mu.g/ml anti-CD28 (Pharmingen) and
3 .mu.g/ml anti-CD3 (OKT3, ATCC) in PBS. After 6 and 24 hours, the
cells were harvested for RNA preparation. To prepare chronically
activated CD8 lymphocytes, we activated the isolated CD8
lymphocytes for 4 days on anti-CD28 and anti-CD3 coated plates and
then harvested the cells and expanded them in DMEM 5% FCS
(Hyclone), 100 .mu.M non essential amino acids (Gibco), 1 mM sodium
pyruvate (Gibco), mercaptoethanol 5.5.times.10.sup.-5M (Gibco), and
10 mM Hepes (Gibco) and IL-2. The expanded CD8 cells were then
activated again with plate bound anti-CD3 and anti-CD28 for 4 days
and expanded as before. RNA was isolated 6 add 24 hours after the
second activation and after 4 days of the second expansion culture.
The isolated NK cells were cultured in DMEM 5% FCS (Hyclone), 100
.mu.M non essential amino acids (Gibco), 1 mM sodium pyruvate
(Gibco), mercaptoethanol 5.5.times.10.sup.-5M (Gibco), and 10 mM
Hepes (Gibco) and IL-2 for 4-6 days before RNA was prepared.
[0468] To obtain B cells, tonsils were procured from NDRI. The
tonsil was cut up with sterile dissecting scissors and then passed
through a sieve. Tonsil cells were then spun down and resupended at
10.sup.6 cells/ml in DMEM 5% FCS (Hyclone), 100 .mu.M non essential
amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol
5.5.times.10.sup.-5M (Gibco), and 10 mM Hepes (Gibco). To activate
the cells, we used PWM at 5 .mu.g/ml or anti-CD40 (Pharmingen) at
approximately 10 .mu.g/ml and IL-4 at 5-10 ng/ml. Cells were
harvested for RNA preparation at 24,48 and 72 hours.
[0469] To prepare the primary and secondary Th1/Th2 and Tr1 cells,
six-well Falcon plates were coated overnight with 10 .mu.g/ml
anti-CD28 (Pharmingen) and 2 .mu.g/ml OKT3 (ATCC), and then washed
twice with PBS. Umbilical cord blood CD4 lymphocytes (Poietic
Systems, German Town, Md.) were cultured at 10.sup.5-10.sup.6
cells/ml in DMEM 5% FCS (Hyclone), 100 .mu.M non essential amino
acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol
5.5.times.10.sup.-5M (Gibco), 10 mM Hepes (Gibco) and IL-2 (4
ng/ml). IL-12 (5 ng/ml) and anti-IL4 (1 .mu.g/ml) were used to
direct to Th1, while IL-4 (5 ng/ml) and anti-IFN gamma (1 .mu.g/ml)
were used to direct to Th2 and IL-10 at 5 ng/ml was used to direct
to Tr1. After 4-5 days, the activated Th1, Th2 and Tr1 lymphocytes
were washed once in DMEM and expanded for 4-7 days in DMEM 5% FCS
(Hyclone), 100 .mu.M non essential amino acids (Gibco), 1 mM sodium
pyruvate (Gibco), mercaptoethanol 5.5.times.10.sup.-5M (Gibco), 10
mM Hepes (Gibco) and IL-2 (1 ng/ml). Following this, the activated
Th1, Th2 and Tr1 lymphocytes were re-stimulated for 5 days with
anti-CD28/OKT3 and cytokines as described above, but with the
addition of anti-CD95L (1 .mu.g/ml) to prevent apoptosis. After 4-5
days, the Th1, Th2 and Tr1 lymphocytes were washed and then
expanded again with IL-2 for 4-7 days. Activated Th1 and Th2
lymphocytes were maintained in this way for a maximum of three
cycles. RNA was prepared from primary and secondary Th1, Th2 and
Tr1 after 6 and 24 hours following the second and third activations
with plate bound anti-CD3 and anti-CD28 mAbs and 4 days into the
second and third expansion cultures in Interleukin 2.
[0470] The following leukocyte cells lines were obtained from the
ATCC: Ramos, EOL-1, KU-812. EOL cells were further differentiated
by culture in 0.1 mM dbcAMP at 5.times.10.sup.5 cells/ml for 8
days, changing the media every 3 days and adjusting the cell
concentration to 5.times.10.sup.5 cells/ml. For the culture of
these cells, we used DMEM or RPMI (as recommended by the ATCC),
with the addition of 5% FCS (Hyclone), 100 .mu.M non essential
amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol
5.5.times.10.sup.-5M (Gibco), 10 mM Hepes (Gibco). RNA was either
prepared from resting cells or cells activated with PMA at 10 ng/ml
and ionomycin at 1 .mu.g/ml for 6 and 14 hours. Keratinocyte line
CCD106 and an airway epithehal tumor line NCI-H292 were also
obtained from the ATCC. Both were cultured in DMEM 5% FCS
(Hyclone), 100 .mu.M non essential amino acids (Gibco), 1 mM sodium
pyruvate (Gibco), mercaptoethanol 5.5.times.10.sup.-5M (Gibco), and
mM Hepes (Gibco). CCD1106 cells were activated for 6 and 14 hours
with approximately 5 ng/ml TNF alpha and 1 ng/ml IL-1 beta, while
NCI-H292 cells were activated for 6 and 14 hours with the following
cytokines: 5 ng/ml IL-4, 5 ng/ml IL-9, 5 ng/ml IL-13 and 25 ng/ml
IFN gamma.
[0471] For these cell lines and blood cells, RNA was prepared by
lysing approximately 10.sup.7 cells/ml using Trizol (Gibco BRL).
Briefly, 1/10 volume of bromochloropropane (Molecular Research
Corporation) was added to the RNA sample, vortexed and after 10
minutes at room temperature, the tubes were spun at 14,000 rpm in a
Sorvall SS34 rotor. The aqueous phase was removed and placed in a
15 ml Falcon Tube. An equal volume of isopropanol was added and
left at -20.degree. C. overnight. The precipitated RNA was spun
down at 9,000 rpm for 15 min in a Sorvall SS34 rotor and washed in
70% ethanol. The pellet was redissolved in 300 .mu.l of RNAse-free
water and 35 .mu.l buffer (Promega) 5 .mu.l DTT, 7 .mu.l RNAsin and
8 .mu.l DNAse were added. The tube was incubated at 37.degree. C.
for 30 minutes to remove contaminating genomic DNA, extracted once
with phenol chloroform and re-precipitated with 1/10 volume of 3M
sodium acetate and 2 volumes of 100% ethanol. The RNA was spun down
and placed in RNAse free water. RNA was stored at -80.degree.
C.
[0472] AI_comprehensive panel_v1.0
[0473] The plates for AI_comprehensive panel_v1.0 include two
control wells and 89 test samples comprised of cDNA isolated from
surgical and postmortem human tissues obtained from the Backus
Hospital and Clinomics (Frederick, Md.). Total RNA was extracted
from tissue samples from the Backus Hospital in the Facility at
CuraGen. Total RNA from other tissues was obtained from
Clinomics.
[0474] Joint tissues including synovial fluid, synovium, bone and
cartilage were obtained from patients undergoing total knee or hip
replacement surgery at the Backus Hospital. Tissue samples were
immediately snap frozen in liquid nitrogen to ensure that isolated
RNA was of optimal quality and not degraded. Additional samples of
osteoarthritis and rheumatoid arthritis joint tissues were obtained
from Clinomics. Normal control tissues were supplied by Clinomics
and were obtained during autopsy of trauma victims.
[0475] Surgical specimens of psoriatic tissues and adjacent matched
tissues were provided as total RNA by Clinomics. Two male and two
female patients were selected between the ages of 25 and 47. None
of the patients were taking prescription drugs at the time samples
were isolated.
[0476] Surgical specimens of diseased colon from patients with
ulcerative colitis and Crohns disease and adjacent matched tissues
were obtained from Clinomics. Bowel tissue from three female and
three male Crohn's patients between the ages of 41-69 were used.
Two patients were not on prescription medication while the others
were taking dexamethasone, phenobarbital, or tylenol. Ulcerative
colitis tissue was from three male and four female patients. Four
of the patients were taking lebvid and two were on
phenobarbital.
[0477] Total RNA from post mortem lung tissue from trauma victims
with no disease or with emphysema, asthma or COPD was purchased
from Clinomics. Emphysema patients ranged in age from 40-70 and all
were smokers, this age range was chosen to focus on patients with
cigarette-linked emphysema and to avoid those patients with alpha-1
anti-trypsin deficiencies. Asthma patients ranged in age from
36-75, and excluded smokers to prevent those patients that could
also have COPD. COPD patients ranged in age from 35-80 and included
both smokers and non-smokers. Most patients were taking
corticosteroids, and bronchodilators.
[0478] In the labels employed to identify tissues in the
Al_comprehensive panel.sub.--v1.0 panel, the following
abbreviations are used: [0479] AI=Autoimmunity [0480] Syn=Synovial
[0481] Normal=No apparent disease [0482] Rep22/Rep20=individual
patients [0483] RA=Rheumatoid arthritis [0484] Backus=From Backus
Hospital [0485] OA=Osteoarthritis [0486] (SS)(BA)(MF)=Individual
patients [0487] Adj=Adjacent tissue [0488] Match control=adjacent
tissues [0489] -M=Male [0490] -F=Female [0491] COPD=Chronic
obstructive pulmonary disease
[0492] Panels 5D and 5I
[0493] The plates for Panel 5D and 5I include two control wells and
a variety of cDNAs isolated from human tissues and cell lines with
an emphasis on metabolic diseases. Metabolic tissues were obtained
from patients enrolled in the Gestational Diabetes study. Cells
were obtained during different stages in the differentiation of
adipocytes from human mesenchymal stem cells. Human pancreatic
islets were also obtained.
[0494] In the Gestational Diabetes study subjects are young (18-40
years), otherwise healthy women with and without gestational
diabetes undergoing routine (elective) Caesarean section. After
delivery of the infant, when the surgical incisions were being
repaired/closed, the obstetrician removed a small sample (<1 cc)
of the exposed metabolic tissues during the closure of each
surgical level. The biopsy material was rinsed in sterile saline,
blotted and fast frozen within 5 minutes from the time of removal.
The tissue was then flash frozen in liquid nitrogen and stored,
individually, in sterile screw-top tubes and kept on dry ice for
shipment to or to be picked up by CuraGen. The metabolic tissues of
interest include uterine wall (smooth muscle), visceral adipose,
skeletal muscle (rectus) and subcutaneous adipose. Patient
descriptions are as follows: [0495] Patient 2: Diabetic Hispanic,
overweight, not on insulin [0496] Patient 7-9: Nondiabetic
Caucasian and obese (BMI>30) [0497] Patient 10: Diabetic
Hispanic, overweight, on insulin [0498] Patient 11: Nondiabetic
African American and overweight [0499] Patient 12: Diabetic
Hispanic on insulin
[0500] Adiocyte differentiation was induced in donor progenitor
cells obtained from Osirus (a division of Clonetics/BioWhittaker)
in triplicate, except for Donor 3U which had only two replicates.
Scientists at Clonetics isolated, grew and differentiated human
mesenchymal stem cells (HuMSCs) for CuraGen based on the published
protocol found in Mark F. Pittenger, et al., Multilineage Potential
of Adult Human Mesenchymal Stem Cells Science Apr. 2, 1999:
143-147. Clonetics provided Trizol lysates or frozen pellets
suitable for mRNA isolation and ds cDNA production. A general
description of each donor is as follows: [0501] Donor 2 and 3 U:
Mesenchymal Stem cells, Undifferentiated Adipose [0502] Donor 2 and
3 AM: Adipose, AdiposeMidway Differentiated [0503] Donor 2 and 3
AD: Adipose, Adipose Differentiated
[0504] Human cell lines were generally obtained from ATCC (American
Type Culture Collection), NCI or the German tumor cell bank and
fall into the following tissue groups: kidney proximal convoluted
tubule, uterine smooth muscle cells, small intestine, liver HepG2
cancer cells, heart primary stromal cells, and adrenal cortical
adenoma cells. These cells are all cultured under standard
recommended conditions and RNA extracted using the standard
procedures. All samples were processed at CuraGen to produce single
stranded cDNA.
[0505] Panel 5I contains all samples previously described with the
addition of pancreatic islets from a 58 year old female patient
obtained from the Diabetes Research Institute at the University of
Miami School of Medicine. Islet tissue was processed to total RNA
at an outside source and delivered to CuraGen for addition to panel
5I.
[0506] In the labels employed to identify tissues in the 5D and 5I
panels, the following abbreviations are used: [0507] GO
Adipose=Greater Omentum Adipose [0508] SK=Skeletal Muscle [0509]
UT=Uterus [0510] PL=Placenta [0511] AD=Adipose Differentiated
[0512] AM=Adipose Midway Differentiated [0513] U=Undifferentiated
Stem Cells
[0514] Panel CNSD.01
[0515] The plates for Panel CNSD.01 include two control wells and
94 test samples comprised of cDNA isolated from postmortem human
brain tissue obtained from the Harvard Brain Tissue Resource
Center. Brains are removed from calvaria of donors between 4 and 24
hours after death, sectioned by neuroanatomists, and frozen at
-80.degree. C. in liquid nitrogen vapor. All brains are sectioned
and examined by neuropathologists to confirm diagnoses with clear
associated neuropathology.
[0516] Disease diagnoses are taken from patient records. The panel
contains two brains from each of the following diagnoses:
Alzheimer's disease, Parkinson's disease, Huntington's disease,
Progressive Supernuclear Palsy, Depression, and "Normal controls".
Within each of these brains, the following regions are represented:
cingulate gyrus, temporal pole, globus palladus, substantia nigra,
Brodman Area 4 (primary motor strip), Brodman Area 7 (parietal
cortex), Brodman Area 9 (prefrontal cortex), and Brodman area 17
(occipital cortex). Not all brain regions are represented in all
cases; e.g., Huntington's disease is characterized in part by
neurodegeneration in the globus palladus, thus this region is
impossible to obtain from confirmed Huntington's cases. Likewise
Parkinson's disease is characterized by degeneration of the
substantia nigra making this region more difficult to obtain.
Normal control brains were examined for neuropathology and found to
be free of any pathology consistent with neurodegeneration.
[0517] In the labels employed to identify tissues in the CNS panel,
the following abbreviations are used: [0518] PSP=Progressive
supranuclear palsy [0519] Sub Nigra=Substantia nigra [0520] Glob
Palladus=Globus palladus [0521] Temp Pole=Temporal pole [0522] Cing
Gyr=Cingulate gyrus [0523] BA 4=Brodman Area 4
[0524] Panel CNS_Neurodegeneration_V1.0
[0525] The plates for Panel CNS_Neurodegeneration_V1.0 include two
control wells and 47 test samples comprised of cDNA isolated from
postmortem human brain tissue obtained from the Harvard Brain
Tissue Resource Center (McLean Hospital) and the Human Brain and
Spinal Fluid Resource Center (VA Greater Los Angeles Healthcare
System). Brains are removed from calvaria of donors between 4 and
24 hours after death, sectioned by neuroanatomists, and frozen at
-80.degree. C. in liquid nitrogen vapor. All brains are sectioned
and examined by neuropathologists to confirm diagnoses with clear
associated neuropathology.
[0526] Disease diagnoses are taken from patient records. The panel
contains six brains from Alzheimer's disease (AD) patients, and
eight brains from "Normal controls" who showed no evidence of
dementia prior to death. The eight normal control brains are
divided into two categories: Controls with no dementia and no
Alzheimer's like pathology (Controls) and controls with no dementia
but evidence of severe Alzheimer's like pathology, (specifically
senile plaque load rated as level 3 on a scale of 0-3; 0=no
evidence of plaques, 3=severe AD senile plaque load). Within each
of these brains, the following regions are represented:
hippocampus, temporal cortex (Brodman Area 21), parietal cortex
(Brodman area 7), and occipital cortex (Brodman area 17). These
regions were chosen to encompass all levels of neurodegeneration in
AD. The hippocampus is a region of early and severe neuronal loss
in AD; the temporal cortex is known to show neurodegeneration in AD
after the hippocampus; the parietal cortex shows moderate neuronal
death in the late stages of the disease; the occipital cortex is
spared in AD and therefore acts as a "control" region within AD
patients. Not all brain regions are represented in all cases.
[0527] In the labels employed to identify tissues in the
CNS_Neurodegeneration_V1.0 panel, the following abbreviations are
used: [0528] AD=Alzheimer's disease brain; patient was demented and
showed AD-like pathology upon autopsy [0529] Control=Control
brains; patient not demented, showing no neuropathology [0530]
Control (Path)=Control brains; pateint not demented but showing
sever AD-like pathology [0531] SupTemporal Ctx=Superior Temporal
Cortex [0532] Inf Temporal Ctx=Inferior Temporal Cortex
[0533] A. NOV2A and NOV2B: LRR Protein
[0534] Expression of gene NOV2A and full length physical clone
NOV2B was assessed using the primer-probe sets Ag4180, Ag6318,
Ag6602, Ag6659 and Ag6702, described in Tables AA, AB, AC, AD and
AE. Please note that NOV2A is recognized by primer-probe set Ag4180
only. Results of the RTQ-PCR runs are shown in Tables AF, AG, AH,
AI, AJ and AK. TABLE-US-00106 TABLE AA Probe Name Ag4180 Start SEQ
ID Primers Sequences Length Position No Forward
5'-tcttccagaaggacatcaactg-3' 22 1347 109 Probe
TET-5'-cagcttcatccacttgagtttccagg-3'- 26 1309 110 TAMRA Reverse
5'-cccctcgtccaggatatagtac-3' 22 1271 111
[0535] TABLE-US-00107 TABLE AB Probe Name Ag6318 Start SEQ ID
Primers Sequences Length Position No Forward
5'-gtagtgaagcaggatagttcataaatagaa-3' 30 3 112 Probe
TET-5'-agtggaagcgccttctcatccttcat-3'- 26 35 113 TAMRA Reverse
5'-gcagtggtcacgtttgga-3' 18 62 114
[0536] TABLE-US-00108 TABLE AC Probe Name Ag6602 Start SEQ Posi- ID
Primers Sequences Length tion No Forward 5'-gtgaggcggcagatcttc-3'
18 426 115 Probe TET-5'- 25 444 116 agctgaatcatctgcagcctgcatt-
3'-TAMRA Reverse 5'-attcccaggcatgatgct-3' 18 495 117
[0537] TABLE-US-00109 TABLE AD Probe Name Ag6659 Start SEQ Posi- ID
Primers Sequences Length tion No Forward 5'-gtgaggcggcagatcttc-3'
18 426 118 Probe TET-5'- 25 444 119 agctgaatcatctgcagcctgcatt-
3'-TAMRA Reverse 5'-attcccaggcatgatgct-3' 18 495 120
[0538] TABLE-US-00110 TABLE AE Probe Name Ag6702 Start SEQ Posi- ID
Primers Sequences Length tion No Forward 5'-gtgaggcggcagatcttc-3'
18 426 121 Probe TET-5'- 25 444 122 agctgaatcatctgcagcctgcatt-
3'-TAMRA Reverse 5'-attcccaggcatgatgct-3' 18 495 123
[0539] TABLE-US-00111 TABLE AF AI_comprehensive panel_v1.0 Rel.
Exp.(%) Rel. Exp.(%) Rel. Exp.(%) Rel. Exp.(%) Ag6318, Run Ag6659,
Run Ag6318, Run Ag6659, Run Tissue Name 275481201 275481281 Tissue
Name 275481201 275481281 110967 COPD-F 5.2 0.0 112427 Match 10.5
0.0 Control Psoriasis-F 110980 COPD-F 0.5 0.0 112418 11.7 0.0
Psoriasis-M 110968 COPD-M 2.5 1.6 112723 Match 0.0 0.0 Control
Psoriasis-M 110977 COPD-M 4.5 4.9 112419 10.7 5.1 Psoriasis-M
110989 5.4 2.1 112424 Match 5.2 0.0 Emphysema-F Control Psoriasis-M
110992 1.4 0.0 112420 8.4 0.0 Emphysema-F Psoriasis-M 110993 2.9
0.0 112425 Match 2.0 0.0 Emphysema-F Control Psoriasis-M 110994 6.1
0.0 104689 (MF) 3.9 18.4 Emphysema-F OA Bone- Backus 110995 2.3 0.0
104690 (MF) 5.5 5.4 Emphysema-F Adj "Normal" Bone-Backus 110996 4.2
0.0 104691 (MF) 8.9 19.3 Emphysema-F OA Synovium- Backus 110997 2.2
0.0 104692 (BA) 1.3 0.0 Asthma-M OA Cartilage- Backus 111001 4.7
2.1 104694 (BA) 6.7 4.5 Asthma-F OA Bone- Backus 111002 6.3 0.0
104695 (BA) 7.1 10.8 Asthma-F Adj "Normal" Bone-Backus 111003
Atopic 4.5 0.0 104696 (BA) 5.0 15.5 Asthma-F OA Synovium- Backus
111004 Atopic 5.4 0.0 104700 (SS) 100.0 100.0 Asthma-F OA Bone-
Backus 111005 Atopic 1.3 0.0 104701 (SS) 8.5 0.0 Asthma-F Adj
"Normal" Bone-Backus 111006 Atopic 0.0 0.0 104702 (SS) 7.0 3.0
Asthma-F OA Synovium- Backus 111417 1.5 0.0 117093 OA 0.8 0.0
Allergy-M Cartilage Rep7 112347 0.5 0.0 112672 OA 8.1 7.6 Allergy-M
Bone5 112349 0.3 0.0 112673 OA 9.7 2.3 Normal Lung-F Synovium5
112357 6.7 10.4 112674 OA 8.2 1.9 Normal Lung-F Synovial Fluid
cells5 112354 2.9 0.0 117100 OA 1.8 0.0 Normal Lung-M Cartilage
Rep14 112374 9.4 3.8 112756 OA 0.2 0.0 Crohns-F Bone9 112389 Match
1.2 0.0 112757 OA 6.3 0.0 Control Synovium9 Crohns-F 112375 2.1 2.6
112758 OA 6.1 6.5 Crohns-F Synovial Fluid Cells9 112732 Match 1.3
0.0 117125 RA 2.9 0.0 Control Cartilage Crohns-F Rep2 112725 3.5
0.0 113492 Bone2 18.7 5.1 Crohns-M RA 112387 Match 0.7 0.0 113493
9.0 2.2 Control Synovium2 Crohns-M RA 112378 1.3 0.0 113494 Syn
15.5 0.0 Crohns-M Fluid Cells RA 112390 Match 5.1 0.0 113499 14.6
1.6 Control Cartilage4 RA Crohns-M 112726 0.6 0.0 113500 Bone4 16.4
0.0 Crohns-M RA 112731 Match 6.2 0.0 113501 14.0 0.0 Control
Synovium4 Crohns-M RA 112380 Ulcer 0.0 0.0 113502 Syn 6.2 0.0 Col-F
Fluid Cells4 RA 112734 Match 17.2 22.8 113495 16.2 2.5 Control
Ulcer Cartilage3 RA Col-F 112384 Ulcer 7.2 0.0 113496 Bone3 20.0
4.3 Col-F RA 112737 Match 3.0 0.0 113497 10.4 1.6 Control Ulcer
Synovium3 Col-F RA 112386 Ulcer 5.3 0.0 113498 Syn 13.9 8.3 Col-F
Fluid Cells3 RA 112738 Match 0.7 0.0 117106 1.1 0.0 Control Ulcer
Normal Col-F Cartilage Rep20 112381 Ulcer 0.0 0.0 113663 Bone3 0.0
0.0 Col-M Normal 112735 Match 0.5 0.0 113664 0.0 0.0 Control Ulcer
Synovium3 Col-M Normal 112382 Ulcer 2.6 0.0 113665 Syn 0.9 0.0
Col-M Fluid Cells3 Normal 112394 Match 2.2 0.0 117107 0.8 0.0
Control Ulcer Normal Col-M Cartilage Rep22 112383 Ulcer 0.7 0.0
113667 Bone4 1.4 0.0 Col-M Normal 112736 Match 1.6 0.0 113668 4.4
0.0 Control Ulcer Synovium4 Col-M Normal 112423 16.7 1.9 113669 Syn
2.0 0.0 Psoriasis-F Fluid Cells4 Normal
[0540] TABLE-US-00112 TABLE AG CNS_neurodegeneration_v1.0 Rel.
Exp.(%) Rel. Exp.(%) Ag4180, Ag4180, Run Run Tissue Name 215539679
Tissue Name 215539679 AD 1 Hippo 7.1 Control (Path) 3 0.0 Temporal
Ctx AD 2 Hippo 0.0 Control (Path) 4 45.4 Temporal Ctx AD 3 Hippo
0.0 AD 1 Occipital 0.0 Ctx AD 4 Hippo 0.0 AD 2 Occipital 0.0 Ctx
(Missing) AD 5 hippo 52.1 AD 3 Occipital 13.3 Ctx AD 6 Hippo 57.0
AD 4 Occipital 15.4 Ctx Control 2 Hippo 17.4 AD 5 Occipital 33.0
Ctx Control 4 Hippo 14.3 AD 6 Occipital 40.9 Ctx Control (Path) 3
14.8 Control 1 55.5 Hippo Occipital Ctx AD 1 Temporal Ctx 16.7
Control 2 0.0 Occipital Ctx AD 2 Temporal Ctx 0.0 Control 3 19.3
Occipital Ctx AD 3 Temporal Ctx 0.0 Control 4 19.1 Occipital Ctx AD
4 Temporal Ctx 0.0 Control (Path) 1 38.4 Occipital Ctx AD 5 Inf
Temporal 25.0 Control (Path) 2 0.0 Ctx Occipital Ctx AD 5
SupTemporal 51.4 Control (Path) 3 0.0 Ctx Occipital Ctx AD 6 Inf
Temporal 0.0 Control (Path) 4 0.0 Ctx Occipital Ctx AD 6 Sup
Temporal 58.6 Control 1 Parietal 0.0 Ctx Ctx Control 1 Temporal
77.9 Control 2 Parietal 0.0 Ctx Ctx Control 2 Temporal 0.0 Control
3 Parietal 0.0 Ctx Ctx Control 3 Temporal 12.7 Control (Path) 1
19.3 Ctx Parietal Ctx Control 4 Temporal 0.0 Control (Path) 2 0.0
Ctx Parietal Ctx Control (Path) 1 16.2 Control (Path) 3 16.7
Temporal Ctx Parietal Ctx Control (Path) 2 0.0 Control (Path) 4
100.0 Temporal Ctx Parietal Ctx
[0541] TABLE-US-00113 TABLE AH General_screening_panel_v1.4 Rel.
Exp.(%) Rel. Exp.(%) Ag4180, Ag4180, Run Run Tissue Name 221118503
Tissue Name 221118503 Adipose 5.1 Renal ca. TK-10 0.9 Melanoma* 0.0
Bladder 0.0 Hs688(A).T Melanoma* 0.4 Gastric ca. (liver met.) 0.0
Hs688(B).T NCI-N87 Melanoma* M14 0.0 Gastric ca. KATO III 0.3
Melanoma* 0.0 Colon ca. SW-948 1.2 LOXIMVI Melanoma* SK- 0.0 Colon
ca. SW480 3.3 MEL-5 Squamous cell 0.0 Colon ca.* (SW480 0.0
carcinoma SCC-4 met) SW620 Testis Pool 8.0 Colon ca. HT29 0.0
Prostate ca.* (bone 1.0 Colon ca. HCT-116 1.1 met) PC-3 Prostate
Pool 0.9 Colon ca. CaCo-2 36.3 Placenta 6.2 Colon cancer tissue 6.3
Uterus Pool 0.0 Colon ca. SW1116 0.0 Ovarian ca. 5.0 Colon ca.
Colo-205 0.0 OVCAR-3 Ovarian ca. SK- 1.1 Colon ca. SW-48 0.0 OV-3
Ovarian ca. 2.4 Colon Pool 3.3 OVCAR-4 Ovarian ca. 1.0 Small
Intestine Pool 0.0 OVCAR-5 Ovarian ca. 1.1 Stomach Pool 2.0 IGROV-1
Ovarian ca. 1.1 Bone Marrow Pool 0.8 OVCAR-8 Ovary 2.1 Fetal Heart
3.9 Breast ca. MCF-7 0.0 Heart Pool 0.0 Breast ca. MDA- 0.0 Lymph
Node Pool 1.8 MB-231 Breast ca. BT 549 0.9 Fetal Skeletal Muscle
0.5 Breast ca. T47D 1.3 Skeletal Muscle Pool 0.0 Breast ca. MDA-N
1.2 Spleen Pool 18.4 Breast Pool 1.7 Thymus Pool 3.5 Trachea 0.0
CNS cancer 100.0 (glio/astro) U87-MG Lung 0.0 CNS cancer 0.0
(glio/astro) U-118-MG Fetal Lung 12.9 CNS cancer 0.0 (neuro; met)
SK-N-AS Lung ca. NCI-N417 0.0 CNS cancer (astro) 0.0 SF-539 Lung
ca. LX-1 0.0 CNS cancer (astro) 0.5 SNB-75 Lung ca. NCI-H146 0.0
CNS cancer (glio) 0.5 SNB-19 Lung ca. SHP-77 0.0 CNS cancer (glio)
SF- 7.0 295 Lung ca. A549 1.0 Brain (Amygdala) 0.0 Pool Lung ca.
NCI-H526 0.0 Brain (cerebellum) 0.0 Lung ca. NCI-H23 0.7 Brain
(fetal) 4.5 Lung ca. NCI-H460 0.0 Brain (Hippocampus) 0.0 Pool Lung
ca. HOP-62 0.0 Cerebral Cortex Pool 0.0 Lung ca. NCI-H522 2.2 Brain
(Substantia 1.0 nigra) Pool Liver 3.0 Brain (Thalamus) Pool 0.0
Fetal Liver 3.1 Brain (whole) 0.0 Liver ca. HepG2 0.0 Spinal Cord
Pool 0.0 Kidney Pool 5.7 Adrenal Gland 4.1 Fetal Kidney 2.8
Pituitary gland Pool 0.0 Renal ca. 786-0 0.0 Salivary Gland 0.6
Renal ca. A498 0.9 Thyroid (female) 7.5 Renal ca. ACHN 0.0
Pancreatic ca. 0.0 CAPAN2 Renal ca. UO-31 0.8 Pancreas Pool 3.0
[0542] TABLE-US-00114 TABLE AI General_screening_panel_v1.5 Rel.
Exp.(%) Rel. Exp.(%) Ag6318, Ag6318, Run Run Tissue Name 259139880
Tissue Name 259139880 Adipose 0.0 Renal ca. TK-10 0.0 Melanoma* 0.0
Bladder 3.1 Hs688(A).T Melanoma* 0.0 Gastric ca. (liver met.) 0.0
Hs688(B).T NCI-N87 Melanoma* M14 0.0 Gastric ca. KATO III 0.0
Melanoma* 0.0 Colon ca. SW-948 0.0 LOXIMVI Melanoma* SK- 0.0 Colon
ca. SW480 2.8 MEL-5 Squamous cell 0.0 Colon ca.* (SW480 0.0
carcinoma SCC-4 met) SW620 Testis Pool 1.0 Colon ca. HT29 0.0
Prostate ca.* (bone 0.0 Colon ca. HCT-116 0.0 met) PC-3 Prostate
Pool 0.5 Colon ca. CaCo-2 77.9 Placenta 1.7 Colon cancer tissue 0.4
Uterus Pool 0.7 Colon ca. SW1116 100.0 Ovarian ca. 0.0 Colon ca.
Colo-205 0.0 OVCAR-3 Ovarian ca. SK- 1.1 Colon ca. SW-48 0.0 OV-3
Ovarian ca. 0.0 Colon Pool 1.2 OVCAR-4 Ovarian ca. 0.0 Small
Intestine Pool 0.0 OVCAR-5 Ovarian ca. 0.0 Stomach Pool 0.0 IGROV-1
Ovarian ca. 0.0 Bone Marrow Pool 0.0 OVCAR-8 Ovary 0.0 Fetal Heart
0.0 Breast ca. MCF-7 0.0 Heart Pool 0.0 Breast ca. MDA- 0.0 Lymph
Node Pool 0.0 MB-231 Breast ca. BT 549 0.0 Fetal Skeletal Muscle
0.4 Breast ca. T47D 0.0 Skeletal Muscle Pool 0.0 Breast ca. MDA-N
0.0 Spleen Pool 0.0 Breast Pool 0.0 Thymus Pool 0.5 Trachea 0.0 CNS
cancer 2.9 (glio/astro) U87-MG Lung 0.0 CNS cancer 0.0 (glio/astro)
U-118-MG Fetal Lung 1.4 CNS cancer 0.0 (neuro; met) SK-N-AS Lung
ca. NCI-N417 0.0 CNS cancer (astro) 0.0 SF-539 Lung ca. LX-1 0.0
CNS cancer (astro) 0.0 SNB-75 Lung ca. NCI-H146 0.0 CNS cancer
(glio) 0.0 SNB-19 Lung ca. SHP-77 0.0 CNS cancer (glio) SF- 0.0 295
Lung ca. A549 0.0 Brain (Amygdala) 0.0 Pool Lung ca. NCI-H526 0.0
Brain (cerebellum) 0.0 Lung ca. NCI-H23 0.0 Brain (fetal) 0.5 Lung
ca. NCI-H460 0.0 Brain (Hippocampus) 0.0 Pool Lung ca. HOP-62 0.0
Cerebral Cortex Pool 1.0 Lung ca. NCI-H522 0.0 Brain (Substantia
0.0 nigra) Pool Liver 0.0 Brain (Thalamus) Pool 0.0 Fetal Liver 0.5
Brain (whole) 0.0 Liver ca. HepG2 0.0 Spinal Cord Pool 0.4 Kidney
Pool 0.5 Adrenal Gland 0.0 Fetal Kidney 1.0 Pituitary gland Pool
0.0 Renal ca. 786-0 0.0 Salivary Gland 0.0 Renal ca. A498 0.0
Thyroid (female) 0.0 Renal ca. ACHN 0.0 Pancreatic ca. 0.9 CAPAN2
Renal ca. UO-31 0.0 Pancreas Pool 0.0
[0543] TABLE-US-00115 TABLE AJ Panel 4.1D Rel. Exp.(%) Rel. Exp.(%)
Ag4180, Ag6318, Rel. Exp.(%) Run Run Ag6602, Run Tissue Name
173607813 259196823 274219626 Secondary Th1 act 0.0 0.0 0.0
Secondary Th2 act 0.0 0.0 0.0 Secondary Tr1 act 0.0 0.0 0.0
Secondary Th1 rest 0.0 0.0 0.0 Secondary Th2 rest 0.0 0.0 0.0
Secondary Tr1 rest 0.0 0.0 0.0 Primary Th1 act 0.0 0.0 0.0 Primary
Th2 act 0.0 0.0 0.0 Primary Tr1 act 0.0 1.7 0.0 Primary Th1 rest
0.0 0.0 0.0 Primary Th2 rest 0.0 0.0 0.0 Primary Tr1 rest 0.2 0.0
0.0 CD45RA CD4 0.3 0.0 0.0 lymphocyte act CD45RO CD4 0.0 0.0 0.0
lymphocyte act CD8 lymphocyte 0.0 0.0 0.0 act Secondary CD8 0.0 0.0
0.0 lymphocyte rest Secondary CD8 0.0 0.0 0.0 lymphocyte act CD4
lymphocyte 0.0 0.0 0.0 none 2ry 0.0 0.0 0.0 Th1/Th2/Tr1_anti- CD95
CH11 LAK cells rest 4.8 3.1 0.6 LAK cells IL-2 0.0 0.0 0.0 LAK
cells IL-2 + IL- 0.0 0.0 0.0 12 LAK cells IL- 0.1 0.0 0.0 2 + IFN
gamma LAK cells IL-2 + IL- 0.0 0.0 0.0 18 LAK cells 1.1 1.0 0.0
PMA/ionomycin NK Cells IL-2 rest 0.3 0.0 0.0 Two Way MLR 3 0.4 1.4
0.0 day Two Way MLR 5 0.0 0.0 0.0 day Two Way MLR 7 0.0 0.0 0.0 day
PBMC rest 23.7 3.1 3.3 PBMC PWM 0.0 0.0 0.0 PBMC PHA-L 0.2 0.0 0.0
Ramos (B cell) 0.0 0.0 0.0 none Ramos (B cell) 0.0 0.0 0.0
ionomycin B lymphocytes 0.0 0.0 0.0 PWM B lymphocytes 0.0 0.0 0.0
CD40L and IL-4 EOL-1 dbcAMP 5.7 2.8 0.4 EOL-1 dbcAMP 0.0 1.3 0.0
PMA/ionomycin Dendritic cells none 4.1 0.6 2.3 Dendritic cells LPS
0.3 0.0 0.0 Dendritic cells anti- 2.4 0.0 0.3 CD40 Monocytes rest
100.0 11.0 7.4 Monocytes LPS 6.4 0.0 1.4 Macrophages rest 0.9 0.0
0.0 Macrophages LPS 0.0 0.0 0.0 HUVEC none 0.0 0.0 0.0 HUVEC
starved 0.0 0.0 0.0 HUVEC IL-1beta 0.0 0.0 0.0 HUVEC IFN 0.0 0.0
0.7 gamma HUVEC TNF alpha + IFN 0.0 0.0 0.0 gamma HUVEC TNF alpha +
IL4 0.0 0.0 0.0 HUVEC IL-11 0.0 0.0 0.0 Lung 0.0 0.0 0.0
Microvascular EC none Lung 0.0 0.0 0.0 Microvascular EC TNF alpha +
IL- 1beta Microvascular 0.0 0.0 0.0 Dermal EC none Microsvasular
0.0 0.0 0.0 Dermal EC TNF alpha + IL- 1beta Bronchial 0.0 0.0 0.0
epithelium TNF alpha + IL1beta Small airway 0.0 0.0 0.0 epithelium
none Small airway 0.0 0.0 0.0 epithelium TNF alpha + IL- 1beta
Coronery artery 0.0 0.0 0.0 SMC rest Coronery artery 0.3 0.0 0.0
SMC TNF alpha + IL- 1beta Astrocytes rest 0.0 0.0 0.0 Astrocytes
0.0 1.9 0.0 TNF alpha + IL- 1beta KU-812 (Basophil) 0.0 0.0 0.0
rest KU-812 (Basophil) 0.0 2.1 0.0 PMA/ionomycin CCD1106 0.0 0.0
0.0 (Keratinocytes) none CCD1106 0.0 0.0 0.0 (Keratinocytes) TNF
alpha + IL- 1beta Liver cirrhosis 0.2 1.0 0.0 NCI-H292 none 0.0 0.0
0.0 NCI-H292 IL-4 0.0 0.0 0.0 NCI-H292 IL-9 0.0 2.7 0.0 NCI-H292
IL-13 0.2 0.0 0.0 NCI-H292 IFN 0.0 0.0 0.0 gamma HPAEC none 0.0 0.0
0.0 HPAEC TNF alpha + IL- 0.0 1.4 0.0 1beta Lung fibroblast 0.0 0.0
0.0 none Lung fibroblast 0.1 0.0 0.0 TNF alpha + IL-1beta Lung
fibroblast IL-4 0.0 0.0 0.0 Lung fibroblast IL-9 0.0 0.0 0.0 Lung
fibroblast IL- 0.0 0.0 0.0 13 Lung fibroblast IFN 0.0 0.0 0.0 gamma
Dermal fibroblast 0.6 0.0 0.0 CCD1070 rest Dermal fibroblast 0.0
0.0 0.0 CCD1070 TNF alpha Dermal fibroblast 0.2 0.0 0.0 CCD1070
IL-1beta Dermal fibroblast 1.9 0.0 0.0 IFN gamma Dermal fibroblast
4.5 0.0 0.0 IL-4 Dermal Fibroblasts 1.2 0.0 0.0 rest Neutrophils
23.8 11.6 17.8 TNFa + LPS Neutrophils rest 68.8 100.0 100.0 Colon
1.0 0.0 0.0 Lung 1.0 1.4 0.0 Thymus 1.9 0.0 0.0 Kidney 17.6 1.2
0.0
[0544] TABLE-US-00116 TABLE AK General oncology screening
panel_v_2.4 Rel. Exp.(%) Rel. Exp.(%) Ag4180, Ag4180, Run Run
Tissue Name 268695204 Tissue Name 268695204 Colon cancer 1 46.0
Bladder cancer NAT 2 0.0 Colon cancer 9.1 Bladder cancer NAT 3 0.0
NAT 1 Colon cancer 2 55.9 Bladder cancer NAT 4 0.0 Colon cancer
11.9 Adenocarcinoma of the 0.0 NAT 2 prostate 1 Colon cancer 3 22.4
Adenocarcinoma of the 4.1 prostate 2 Colon cancer 6.7
Adenocarcinoma of the 0.0 NAT 3 prostate 3 Colon malignant 49.7
Adenocarcinoma of the 1.7 cancer 4 prostate 4 Colon normal 0.0
Prostate cancer NAT 5 0.0 adjacent tissue 4 Lung cancer 1 100.0
Adenocarcinoma of the 0.0 prostate 6 Lung NAT 1 13.8 Adenocarcinoma
of the 3.5 prostate 7 Lung cancer 2 11.9 Adenocarcinoma of the 0.0
prostate 8 Lung NAT 2 5.7 Adenocarcinoma of the 16.0 prostate 9
Squamous cell 10.3 Prostate cancer NAT 0.0 carcinoma 3 10 Lung NAT
3 6.3 Kidney cancer 1 44.1 metastatic 32.8 KidneyNAT 1 3.9 melanoma
1 Melanoma 2 4.1 Kidney cancer 2 65.1 Melanoma 3 2.7 Kidney NAT 2
2.1 metastatic 48.3 Kidney cancer 3 0.0 melanoma 4 metastatic 51.8
Kidney NAT 3 0.0 melanoma 5 Bladder cancer 1 9.2 Kidney cancer 4
47.6 Bladder cancer 0.0 Kidney NAT 4 33.0 NAT 1 Bladder cancer 2
0.0
[0545] AI_comprehensive panel_v1.0 Summary: Ag6318/Ag6659 Two
experiments with two different probe and primer sets that are
specific to the NOV2B variant produce results that are in
reasonable agreement. Highest expression of this gene is seen in
bone from an OA patient (CTs=30-34). Expression levels in the other
samples in the Ag6659 experiment are below the threshold of
reliable detection. In the experiment using probe and primer set
Ag6318, low but significant levels of expression are seen in many
of the samples on this panel, including bone, synovium, synovial
fluid and cartilage from OA and RA patients. These results confirm
expression of this gene in samples related to the autoimmune
response. Thus, therapeutic modulation of the expression or
function of this gene or gene product may be useful in the
treatment of OA.
[0546] CNS_neurodegeneration_v1.0 Summary: Ag4180 This panel does
not show differential expression of this gene in Alzheimer's
disease. However, this expression profile confirms the presence of
this gene in the brain. This gene encodes a leucine-rich repeat
protein. Leucine rich repeats (LRR) mediate reversible
protein-protein interactions and have diverse cellular functions,
including cellular adhesion and signaling. Several of these
proteins, such as connectin, slit, chaoptin, and Toll have pivotal
roles in neuronal development in Drosophila and may play
significant but distinct roles in neural development and in the
adult nervous system of humans (Battye R. (2001) J. Neurosci. 21:
4290-4298. Itoh A. (1998) Brain Res. Mol. Brain Res. 62: 175-186).
In Drosophilia, the LRR region of axon guidance proteins has been
shown to be critical for their function (especially in axon
repulsion). Since the leucine-rich-repeat protein encoded by this
gene shows high expression in the cerebral cortex, it is an
excellent candidate neuronal guidance protein for axons, dendrites
and/or growth cones in general. Therefore, therapeutic modulation
of the levels of this protein, or possible signaling via this
protein, may be of utility in enhancing/directing compensatory
synaptogenesis and fiber growth in the CNS in response to neuronal
death (stroke, head trauma), axon lesion (spinal cord injury), or
neurodegeneration (Alzheimer's, Parkinson's, Huntington's, vascular
dementia or any neurodegenerative disease). A second experiment
with Ag6318 shows low/undetectable levels of expression in all
samples on this panel. (CTS>35). (Data not shown.)
[0547] General_screening_panel_v1.4 Summary: Ag4180 Highest
expression of this gene is seen in a brain cancer cell line
(CT=30.8). Low but significant expression is also seen in colon
cancer. Thus, expression of this gene could be used to
differentiate between these samples and other samples on this panel
and as a marker to detect the presence of these cancers. Members of
the leucine rich superfamily have been shown to be upregulated in
some brain cancers (Almeida A, Oncogene 1998 Jun. 11; 16
(23):2997-3002) Therefore, therapeutic modulation of the expression
or function of this gene may be effective in the treatment of brain
and colon cancer.
[0548] Low but significant expression is also seen in the thyroid.
The extracellular domains of receptors for glycoprotein hormones
that influence the development and function of the thyroid are
members of the leucine-rich repeat (LRR) protein superfamily and
are responsible for the high-affinity binding. (Jiang X. (1995)
Structure 3: 1341-1353.) Thus, therapeutic modulation of this gene
product may aid in the treatment of metabolic and neuroendocrine
disorders.
[0549] General_screening_panel_v1.5 Summary: Ag6318 This probe and
primer set is specific for the NOV2B variant only and produces a
different expression profile than in Panel 1.4. In this panel,
expression is exclusive to colon cancer cell lines (CTs=32). Thus,
expression of this gene could be used to differentiate between this
sample and other samples on this panel and as a marker to detect
the presence of colon cancer. Furthermore, therapeutic modulation
of the expression or function of this gene may be effective in the
treatment of colon cancer.
[0550] General_screening_panel_v1.6 Summary: Ag6702 Expression is
low/undetectable in all samples on this panel. (CTs>35). (Data
not shown.)
[0551] Panel 4.1D Summary: Ag4180 Expression of this gene is
highest in resting monocytes (CT=28.7). Moderate levels of
expression are seen in resting PBMCs, resting neutrophils
(CT=29.2), TNF-a and LPS treated neutrophils (CT=30.7), and normal
kidney. Low but significant levels of expression are seen in
activated dermal fibroblasts, resting LAK cells, LPS treated
monocytes, eosinophils and treated dendritic cells.
[0552] Two experiments with the probe and primer sets Ag6318 and
Ag6602, both specific to NOV2B, show expression in resting
neutrophils only (CTs=31-32).
[0553] The expression of this transcript in LPS treated monocytes,
cells that play a crucial role in linking innate immunity to
adaptive immunity, suggests a role for this gene product in
initiating inflammatory reactions. Therefore, modulation of the
expression or activity of the NOV2A gene may reduce or prevent
early stages of inflammation and reduce the severity of
inflammatory diseases such as psoriasis, asthma, inflammatory bowel
disease, rheumatoid arthritis, osteoarthritis and other lung
inflammatory diseases.
[0554] General oncology screening panel_v.sub.--2.4 Summary: Ag4180
Highest expression of this gene is seen in lung cancer (CT=33.5).
In addition, expression is higher in lung, colon and kidney cancers
when compared to expression in the corresponding normal adjacent
tissue. Thus, expression of this gene could be as a marker to
detect the presence of these cancers. Furthermore, therapeutic
modulation of the expression or function of this gene may be
effective in the treatment of lung, colon and kidney cancer.
[0555] B. NOV3A: Gonadotrophin Beta-Subunit
[0556] Expression of gene NOV3A was assessed using the primer-probe
sets Ag338 and Ag74, described in Tables BA and BB. Results of the
RTQ-PCR runs are shown in Table BC. TABLE-US-00117 TABLE BA Probe
Name Ag338 Start SEQ ID Primers Sequences Length Position No
Forward 5'-acaacgagaccaaacaggtgact-3' 23 248 124 Probe
TET-5'-tcaagctgcccaactgtgcccc-3'- 22 272 125 TAMRA Reverse
5'-ggccacgggataggtgtaga-3' 20 308 126
[0557] TABLE-US-00118 TABLE BB Probe Name Ag74 Start SEQ ID Primers
Sequences Length Position No Forward 5'-acaacgagaccaaacaggtgact-3'
23 248 127 Probe TET-5'-caactgtgccccgggagtcgac-3'- 22 282 128 TAMRA
Reverse 5'-ggccacgggataggtgtaga-3' 20 308 129
[0558] TABLE-US-00119 TABLE BC Panel 1 Rel. Exp.(%) Rel. Exp.(%)
Ag338, Ag74, Tissue Name Run 97805375 Run 87354633 Endothelial
cells 0.0 0.0 Endothelial cells (treated) 0.0 0.0 Pancreas 0.0 0.0
Pancreatic ca. CAPAN 2 0.0 0.0 Adrenal gland 0.0 0.0 Thyroid 0.0
0.0 Salivary gland 0.0 0.0 Pituitary gland 0.0 0.0 Brain (fetal)
0.0 0.0 Brain (whole) 0.5 0.0 Brain (amygdala) 0.6 0.0 Brain
(cerebellum) 0.3 24.8 Brain (hippocampus) 0.0 0.0 Brain (substantia
nigra) 0.0 0.0 Brain (thalamus) 0.1 0.0 Brain (hypothalamus) 0.0
0.0 Spinal cord 0.0 0.0 glio/astro U87-MG 0.0 0.0 glio/astro
U-118-MG 0.0 0.0 astrocytoma SW1783 0.0 0.0 neuro*; met SK-N-AS 0.0
0.0 astrocytoma SF-539 0.0 0.0 astrocytoma SNB-75 0.0 0.0 glioma
SNB-19 0.0 0.0 glioma U251 0.0 0.0 glioma SF-295 0.0 0.0 Heart 0.0
0.0 Skeletal muscle 0.0 0.0 Bone marrow 0.0 0.0 Thymus 0.0 0.0
Spleen 0.0 0.0 Lymph node 0.0 0.0 Colon (ascending) 23.2 40.3
Stomach 0.0 0.0 Small intestine 0.0 0.0 Colon ca. SW480 0.0 0.0
Colon ca.* SW620 (SW480 met) 0.0 0.0 Colon ca. HT29 0.0 0.0 Colon
ca. HCT-116 0.0 0.0 Colon ca. CaCo-2 0.0 0.0 Colon ca. HCT-15 1.7
0.0 Colon ca. HCC-2998 0.0 0.0 Gastric ca.* (liver met) NCI-N87 0.0
0.0 Bladder 0.0 0.0 Trachea 0.0 0.0 Kidney 0.0 0.0 Kidney (fetal)
0.0 0.0 Renal ca. 786-0 0.0 0.0 Renal ca. A498 0.0 0.0 Renal ca.
RXF 393 0.0 0.0 Renal ca. ACHN 0.0 0.0 Renal ca. UO-31 0.0 0.0
Renal ca. TK-10 0.0 0.0 Liver 0.0 0.0 Liver (fetal) 0.0 0.0 Liver
ca. (hepatoblast) HepG2 0.0 0.0 Lung 0.0 0.0 Lung (fetal) 0.0 0.0
Lung ca. (small cell) LX-1 0.0 0.0 Lung ca. (small cell) NCI-H69
8.4 4.6 Lung ca. (s. cell var.) SHP-77 0.0 0.0 Lung ca. (large
cell) NCI-H460 0.0 0.0 Lung ca. (non-sm. cell) A549 0.4 0.0 Lung
ca. (non-s. cell) NCI-H23 0.0 0.0 Lung ca. (non-s. cell) HOP-62 0.0
0.0 Lung ca. (non-s. cl) NCI-H522 0.0 0.0 Lung ca. (squam.) SW 900
0.0 0.0 Lung ca. (squam.) NCI-H596 1.8 0.0 Mammary gland 0.0 0.0
Breast ca.* (pl. ef) MCF-7 0.0 0.0 Breast ca.* (pl. ef) MDA-MB-231
0.0 0.0 Breast ca.* (pl. ef) T47D 1.1 18.6 Breast ca. BT-549 0.0
0.0 Breast ca. MDA-N 0.0 0.0 Ovary 0.0 0.0 Ovarian ca. OVCAR-3 0.0
0.0 Ovarian ca. OVCAR-4 0.0 0.0 Ovarian ca. OVCAR-5 10.3 4.8
Ovarian ca. OVCAR-8 0.0 0.0 Ovarian ca. IGROV-1 1.5 0.0 Ovarian ca.
(ascites) SK-OV-3 0.0 0.0 Uterus 0.0 0.0 Placenta 0.0 0.0 Prostate
0.0 0.0 Prostate ca.* (bone met) PC-3 0.5 0.0 Testis 5.8 100.0
Melanoma Hs688(A).T 0.0 0.0 Melanoma* (met) Hs688(B).T 0.0 0.0
Melanoma UACC-62 0.0 0.0 Melanoma M14 0.0 1.0 Melanoma LOX IMVI 0.0
0.0 Melanoma* (met) SK-MEL-5 0.0 0.0 Melanoma SK-MEL-28 100.0
0.0
[0559] CNS_neurodegeneration_v1.0 Summary: Ag338 Results from one
experiment with the NOV3A gene are not included. The amp plot
indicates that there were experimental difficulties with this
run.
[0560] Panel 1 Summary: Ag338 Highest expression of the NOV3A gene
is detected in a melanoma SK-MEL-28 cell line (CT=27.8). Thus,
expression of this gene may be used to distinguish this sample from
other samples used in this panel. In addition, low to moderate
expression of this gene is also seen in lung cancer, breast cancer
and ovarian cancer cell lines. Therefore, therapeutic modulation of
this gene product may be useful in the treatment of these
cancers.
[0561] Low expression of this gene is also seen in testis and
colon. Therefore, therapeutic modulation of this gene product may
be useful in the treatment of diseases associated testis and colon
such as fertility, hypogonadism, inflammatory bowel diseases,
cancers.
[0562] Ag74 Highest expression of the NOV3A gene is detected in
testis (CT=31.4). Thus, expression of this gene can be used to
distinguish this sample from other samples in this panel. In
addition, moderate expression of this gene is also seen in colon
and brain (cerebellum). Therefore, therapeutic modulation of this
gene product may be useful in the treatment of neurological
disorders and diseases associated with testis and colon.
[0563] Panel 4D Summary: Ag338 Expression of the NOV3A gene is
low/undetectable (CTs>35) across all of the samples on this
panel (data not shown).
[0564] General oncology screening panel_v.sub.--2.4 Summary: Ag338
Expression of the NOV3A gene is low/undetectable (CTs>35) across
all of the samples on this panel (data not shown).
[0565] C. NOV4A: Odorant Binding Protein
[0566] Expression of gene NOV4A was assessed using the primer-probe
sets Ag4218 and Ag4261, described in Tables CA and CB. Results of
the RTQ-PCR runs are shown in Tables CC and CD. TABLE-US-00120
TABLE CA Probe Name Ag4218 Start SEQ ID Primers Sequences Length
Position No Forward 5'-actctcggaggaggacatttt3' 21 339 130 Probe
TET-5'-cagtcccctgtgtccctctgctg-3'- 23 394 131 TAMRA Reverse
5'-cactggagatagcagacagaca-3' 22 417 132
[0567] TABLE-US-00121 TABLE CB Probe Name Ag4261 Start SEQ ID
Primers Sequences Length Position No Forward
5'-actctcggaggaggacatttt-3' 21 339 133 Probe
TET-5'-cagtcccctgtgtccctctgctg-3'- 23 394 134 TAMRA Reverse
5'-cactggagatagcagacagaca-3' 22 417 135
[0568] TABLE-US-00122 TABLE CC General_screening_panel_v1.4 Rel.
Exp.(%) Rel. Exp.(%) Ag4261, Ag4261, Run Run Tissue Name 222523498
Tissue Name 222523498 Adipose 0.0 Renal ca. TK-10 0.0 Melanoma* 0.0
Bladder 0.0 Hs688(A).T Melanoma* 0.0 Gastric ca. (liver met.) 2.5
Hs688(B).T NCI-N87 Melanoma* M14 0.0 Gastric ca. KATO III 100.0
Melanoma* 0.0 Colon ca. SW-948 1.5 LOXIMVI Melanoma* SK- 0.0 Colon
ca. SW480 0.0 MEL-5 Squamous cell 0.0 Colon ca.* (SW480 0.0
carcinoma SCC-4 met) SW620 Testis Pool 0.0 Colon ca. HT29 0.0
Prostate ca.* (bone 0.0 Colon ca. HCT-116 0.0 met) PC-3 Prostate
Pool 0.0 Colon ca. CaCo-2 0.0 Placenta 0.0 Colon cancer tissue 0.0
Uterus Pool 0.0 Colon ca. SW1116 0.0 Ovarian ca. 0.0 Colon ca.
Colo-205 0.0 OVCAR-3 Ovarian ca. SK- 13.4 Colon ca. SW-48 0.0 OV-3
Ovarian ca. 0.0 Colon Pool 7.0 OVCAR-4 Ovarian ca. 0.0 Small
Intestine Pool 5.7 OVCAR-5 Ovarian ca. 0.0 Stomach Pool 0.9 IGROV-1
Ovarian ca. 0.0 Bone Marrow Pool 8.4 OVCAR-8 Ovary 0.0 Fetal Heart
0.4 Breast ca. MCF-7 0.0 Heart Pool 0.0 Breast ca. MDA- 0.0 Lymph
Node Pool 0.0 MB-231 Breast ca. BT 549 0.0 Fetal Skeletal Muscle
0.0 Breast ca. T47D 0.0 Skeletal Muscle Pool 0.0 Breast ca. MDA-N
0.0 Spleen Pool 0.0 Breast Pool 0.0 Thymus Pool 0.0 Trachea 0.0 CNS
cancer 0.0 (glio/astro) U87-MG Lung 0.0 CNS cancer 0.0 (glio/astro)
U-118-MG Fetal Lung 2.6 CNS cancer 0.0 (neuro; met) SK-N-AS Lung
ca. NCI-N417 0.0 CNS cancer (astro) 0.0 SF-539 Lung ca. LX-1 4.2
CNS cancer (astro) 0.0 SNB-75 Lung ca. NCI-H146 0.0 CNS cancer
(glio) 0.0 SNB-19 Lung ca. SHP-77 0.0 CNS cancer (glio) 0.0 SF-295
Lung ca. A549 0.0 Brain (Amygdala) 0.0 Pool Lung ca. NCI-H526 0.0
Brain (cerebellum) 0.0 Lung ca. NCI-H23 0.0 Brain (fetal) 0.0 Lung
ca. NCI-H460 0.0 Brain (Hippocampus) 0.0 Pool Lung ca. HOP-62 0.0
Cerebral Cortex Pool 0.0 Lung ca. NCI-H522 0.0 Brain (Substantia
0.0 nigra) Pool Liver 0.0 Brain (Thalamus) Pool 0.0 Fetal Liver 0.0
Brain (whole) 0.0 Liver ca. HepG2 0.0 Spinal Cord Pool 0.0 Kidney
Pool 0.0 Adrenal Gland 0.0 Fetal Kidney 1.9 Pituitary gland Pool
0.0 Renal ca. 786-0 0.0 Salivary Gland 0.0 Renal ca. A498 0.0
Thyroid (female) 0.0 Renal ca. ACHN 0.0 Pancreatic ca. 0.0 CAPAN2
Renal ca. UO-31 0.0 Pancreas Pool 0.0
[0569] TABLE-US-00123 TABLE CD Panel 4.1D Rel. Exp.(%) Rel. Exp.(%)
Ag4218, Run Ag4218, Run Tissue Name 174261203 Tissue Name 174261203
Secondary Th1 act 0.0 HUVEC IL-1beta 0.0 Secondary Th2 act 0.0
HUVEC IFN gamma 0.0 Secondary Tr1 act 0.0 HUVEC TNF alpha + IFN 1.4
gamma Secondary Th1 rest 0.0 HUVEC TNF alpha + IL4 0.0 Secondary
Th2 rest 0.0 HUVEC IL-11 0.0 Secondary Tr1 rest 0.0 Lung
Microvascular EC 0.0 none Primary Th1 act 2.0 Lung Microvascular EC
0.0 TNF alpha + IL-1beta Primary Th2 act 0.0 Microvascular Dermal
0.0 EC none Primary Tr1 act 0.0 Microsvasular Dermal 0.0 EC TNF
alpha + IL-1beta Primary Th1 rest 0.0 Bronchial epithelium 2.3 TNF
alpha + IL1beta Primary Th2 rest 0.0 Small airway epithelium 0.0
none Primary Tr1 rest 0.9 Small airway epithelium 0.0 TNF alpha +
IL-1beta CD45RA CD4 0.0 Coronery artery SMC 0.0 lymphocyte act rest
CD45RO CD4 0.9 Coronery artery SMC 0.0 lymphocyte act TNF alpha +
IL-1beta CD8 lymphocyte act 0.0 Astrocytes rest 0.0 Secondary CD8
1.0 Astrocytes TNF alpha + IL- 0.0 lymphocyte rest 1beta Secondary
CD8 0.0 KU-812 (Basophil) rest 1.3 lymphocyte act CD4 lymphocyte
none 0.0 KU-812 (Basophil) 0.0 PMA/ionomycin 2ry Th1/Th2/Tr1_anti-
0.0 CCD1106 0.0 CD95 CH11 (Keratinocytes) none LAK cells rest 0.0
CCD1106 0.0 (Keratinocytes) TNF alpha + IL-1beta LAK cells IL-2 0.0
Liver cirrhosis 0.0 LAK cells IL-2 + IL-12 0.0 NCI-H292 none 2.4
LAK cells IL-2 + IFN 0.0 NCI-H292 IL-4 0.0 gamma LAK cells IL-2 +
IL-18 0.0 NCI-H292 IL-9 0.0 LAK cells 0.0 NCI-H292 IL-13 0.0
PMA/ionomycin NK Cells IL-2 rest 0.0 NCI-H292 IFN gamma 0.0 Two Way
MLR 3 day 0.0 HPAEC none 0.0 Two Way MLR 5 day 0.0 HPAEC TNF alpha
+ IL- 0.0 1beta Two Way MLR 7 day 0.0 Lung fibroblast none 0.0 PBMC
rest 0.0 Lung fibroblast TNF 0.0 alpha + IL-1beta PBMC PWM 0.0 Lung
fibroblast IL-4 0.0 PBMC PHA-L 0.0 Lung fibroblast IL-9 0.0 Ramos
(B cell) none 0.0 Lung fibroblast IL-13 2.5 Ramos (B cell) 0.0 Lung
fibroblast IFN 0.0 ionomycin gamma B lymphocytes PWM 0.0 Dermal
fibroblast 0.0 CCD1070 rest B lymphocytes CD40L 0.0 Dermal
fibroblast 0.0 and IL-4 CCD1070 TNF alpha EOL-1 dbcAMP 0.0 Dermal
fibroblast 0.0 CCD1070 IL-1beta EOL-1 dbcAMP 0.0 Dermal fibroblast
IFN 0.0 PMA/ionomycin gamma Dendritic cells none 0.0 Dermal
fibroblast IL-4 1.4 Dendritic cells LPS 0.0 Dermal Fibroblasts rest
1.3 Dendritic cells anti- 3.4 Neutrophils TNFa + LPS 0.0 CD40
Monocytes rest 0.0 Neutrophils rest 0.0 Monocytes LPS 0.0 Colon 0.0
Macrophages rest 0.0 Lung 3.1 Macrophages LPS 0.0 Thymus 14.9 HUVEC
none 0.0 Kidney 100.0 HUVEC starved 0.0
[0570] CNS_neurodegeneration_v1.0 Summary: Ag4218 Expression of the
NOV4A gene is low/undetectable in all samples on this panel
(CTs>35). (Data not shown.)
[0571] General_screening_panel_v1.4 Summary: Ag4218 Expression of
the NOV4A gene is restricted to a sample derived from a gastric
cancer cell line (CT=32). Thus, expression of this gene could be
used to differentiate between this sample and other samples on this
panel and as a marker to detect the presence of gastric cancer.
Furthermore, therapeutic modulation of the expression or function
of this gene may be effective in the treatment of gastric
cancer.
[0572] Panel 4.1D Summary: Ag4218 Expression of the NOV4A gene is
limited to the kidney and thymus (CTs=30-33). Therefore,
therapeutic modulation of the expression or function of this gene
may modulate kidney and thymus function and be important in the
treatment of inflammatory or autoimmune diseases that affect these
organs, including lupus and glomerulonephritis.
[0573] General oncology screening panel_v.sub.--2.4 Summary: Ag4218
Expression of the NOV4A gene is low/undetectable in all samples on
this panel (CTs>35). (Data not shown.)
[0574] D. NOV6B: Cathepsin F Precursor
[0575] Expression of gene NOV6B, representing a full-length
physical clone, was assessed using the primer-probe set Ag6946,
described in Table DA. Results of the RTQ-PCR runs are shown in
Table DB. TABLE-US-00124 TABLE DA Probe Name Ag6946 Start SEQ ID
Primers Sequences Length Position No Forward
5'-ccagccccaagtcctggat-3' 19 80 136 Probe
TET-5'-aaccttggtgtccactgggccaca-3'- 24 132 137 TAMRA Reverse
5'-atcatggctgagccctgagt-3' 20 186 138
[0576] TABLE-US-00125 TABLE DB General_screening_panel_v1.6 Rel.
Exp.(%) Rel. Exp.(%) Ag6946, Ag6946, Run Run Tissue Name 278388882
Tissue Name 278388882 Adipose 11.4 Renal ca. TK-10 0.0 Melanoma*
21.0 Bladder 10.2 Hs688(A).T Melanoma* 13.4 Gastric ca. (liver
met.) 5.2 Hs688(B).T NCI-N87 Melanoma* M14 26.1 Gastric ca. KATO
III 0.0 Melanoma* 1.4 Colon ca. SW-948 1.4 LOXIMVI Melanoma* SK-
18.7 Colon ca. SW480 0.0 MEL-5 Squamous cell 3.4 Colon ca.* (SW480
0.0 carcinoma SCC-4 met) SW620 Testis Pool 29.7 Colon ca. HT29 0.0
Prostate ca.* (bone 17.0 Colon ca. HCT-116 0.0 met) PC-3 Prostate
Pool 12.4 Colon ca. CaCo-2 0.0 Placenta 12.3 Colon cancer tissue
3.3 Uterus Pool 7.2 Colon ca. SW1116 0.0 Ovarian ca. 36.6 Colon ca.
Colo-205 0.0 OVCAR-3 Ovarian ca. SK- 18.8 Colon ca. SW-48 0.1 OV-3
Ovarian ca. 2.2 Colon Pool 23.8 OVCAR-4 Ovarian ca. 7.9 Small
Intestine Pool 23.0 OVCAR-5 Ovarian ca. 10.8 Stomach Pool 13.4
IGROV-1 Ovarian ca. 20.7 Bone Marrow Pool 6.8 OVCAR-8 Ovary 32.8
Fetal Heart 3.5 Breast ca. MCF-7 1.5 Heart Pool 11.1 Breast ca.
MDA- 22.2 Lymph Node Pool 19.1 MB-231 Breast ca. BT 549 53.2 Fetal
Skeletal Muscle 2.8 Breast ca. T47D 15.3 Skeletal Muscle Pool 4.5
Breast ca. MDA-N 26.8 Spleen Pool 6.2 Breast Pool 22.8 Thymus Pool
11.1 Trachea 14.9 CNS cancer 7.0 (glio/astro) U87-MG Lung 5.1 CNS
cancer 1.2 (glio/astro) U-118-MG Fetal Lung 10.5 CNS cancer 7.4
(neuro; met) SK-N-AS Lung ca. NCI-N417 1.1 CNS cancer (astro) 1.8
SF-539 Lung ca. LX-1 0.2 CNS cancer (astro) 36.9 SNB-75 Lung ca.
NCI-H146 1.4 CNS cancer (glio) 11.0 SNB-19 Lung ca. SHP-77 11.4 CNS
cancer (glio) SF- 62.4 295 Lung ca. A549 15.0 Brain (Amygdala) 20.9
Pool Lung ca. NCI-H526 4.8 Brain (cerebellum) 100.0 Lung ca.
NCI-H23 35.4 Brain (fetal) 17.9 Lung ca. NCI-H460 10.7 Brain
(Hippocampus) 24.1 Pool Lung ca. HOP-62 30.6 Cerebral Cortex Pool
35.4 Lung ca. NCI-H522 0.0 Brain (Substantia 25.0 nigra) Pool Liver
13.6 Brain (Thalamus) Pool 33.2 Fetal Liver 4.9 Brain (whole) 26.1
Liver ca. HepG2 0.0 Spinal Cord Pool 28.1 Kidney Pool 50.0 Adrenal
Gland 25.7 Fetal Kidney 11.2 Pituitary gland Pool 6.2 Renal ca.
786-0 0.0 Salivary Gland 18.4 Renal ca. A498 8.9 Thyroid (female)
12.2 Renal ca. ACHN 0.0 Pancreatic ca. 6.0 CAPAN2 Renal ca. UO-31
10.7 Pancreas Pool 4.8
[0577] General_screening_panel_v1.6 Summary: Ag6946 Highest
expression of the NOV6B gene is seen in the cerebellum (CT=28.3).
In addition, moderate levels of expression are also seen in all
regions of the CNS examined. This gene encodes a homolog of
cathepsin that has been shown to be deficient in neurodegenerative
lysosomal disorder galactosialidosis, which produces nephropathy,
ataxia, and premature death. Expression of cathepsin in the brain
has been shown to delay the onset of the neuronal degeneration and
to correct the ataxia associated with this disease. (Leimig T.
Blood 2002 May 1; 99 (9):3169-78). Thus, based on the expression of
this gene in the CNS and the homology that this gene shows to
cathepsin, modulation of this gene could be used in the treatment
of this disorder, diseases that affect the cerebellum such as
autism and the ataxias, Alzheimer's disease, Parkinson's disease,
schizophrenia, multiple sclerosis, stroke and epilepsy.
[0578] Moderate levels of expression are also seen in cell lines
derived from ovarian cancer, lung cancer and breast cancer. Thus,
therapeutic modulation of the expression or function of this gene
may be effective in the treatment of these cancers.
[0579] Among tissues with metabolic function, this gene is
expressed at moderate to low levels in pituitary, adipose, adrenal
gland, pancreas, thyroid, and adult and fetal skeletal muscle,
heart, and liver. This widespread expression among these tissues
suggests that this gene product may play a role in normal
neuroendocrine and metabolic function and that disregulated
expression of this gene may contribute to neuroendocrine disorders
or metabolic diseases, such as obesity and diabetes.
[0580] E. NOV7A: Netrin G1
[0581] Expression of gene NOV7A was assessed using the primer-probe
set Ag4235, described in Table EA. Results of the RTQ-PCR runs are
shown in Tables EB, EC, ED, EE and EF. TABLE-US-00126 TABLE EA
Probe Name Ag4235 Start SEQ ID Primers Sequences Length Position No
Forward 5'-ggtcatggtcctggagaagt-3' 20 537 139 Probe
TET-5'-acctggcagccctaccagttctacg-3'- 25 574 140 TAMRA Reverse
5'-acataccgaaggcctccat-3' 19 610 141
[0582] TABLE-US-00127 TABLE EB CNS_neurodegeneration_v1.0 Rel.
Exp.(%) Rel. Exp.(%) Ag4235, Run Ag4235, Run Tissue Name 224078156
230510266 AD 1 Hippo 11.7 30.1 AD 2 Hippo 26.8 47.0 AD 3 Hippo 5.0
16.8 AD 4 Hippo 4.6 17.0 AD 5 Hippo 27.5 77.9 AD 6 Hippo 16.3 68.8
Control 2 Hippo 14.3 37.6 Control 4 Hippo 14.2 51.4 Control (Path)
3 Hippo 4.5 0.0 AD 1 Temporal Ctx 7.5 9.1 AD 2 Temporal Ctx 15.0
39.2 AD 3 Temporal Ctx 4.8 12.9 AD 4 Temporal Ctx 9.2 10.8 AD 5 Inf
Temporal Ctx 31.6 100.0 AD 5 Sup Temporal Ctx 22.4 89.5 AD 6 Inf
Temporal Ctx 18.0 58.2 AD 6 Sup Temporal Ctx 17.7 55.1 Control 1
Temporal Ctx 7.2 13.5 Control 2 Temporal Ctx 18.6 55.5 Control 3
Temporal Ctx 8.4 29.9 Control 3 Temporal Ctx 12.7 38.2 Control
(Path) 1 49.0 67.4 Temporal Ctx Control (Path) 2 14.8 50.0 Temporal
Ctx Control (Path) 3 9.5 14.5 Temporal Ctx Control (Path) 4 26.4
59.9 Temporal Ctx AD 1 Occipital Ctx 6.1 15.2 AD 2 Occipital Ctx
0.0 0.0 (Missing) AD 3 Occipital Ctx 5.6 11.0 AD 4 Occipital Ctx
6.7 20.7 AD 5 Occipital Ctx 14.7 39.8 AD 6 Occipital Ctx 4.0 4.8
Control 1 Occipital Ctx 3.2 13.3 Control 2 Occipital Ctx 15.0 50.0
Control 3 Occipital Ctx 7.4 24.8 Control 4 Occipital Ctx 4.9 16.4
Control (Path) 1 33.9 81.2 Occipital Ctx Control (Path) 2 7.1 0.5
Occipital Ctx Control (Path) 3 3.2 6.6 Occipital Ctx Control (Path)
4 15.3 41.5 Occipital Ctx Control 1 Parietal Ctx 6.9 21.9 Control 2
Parietal Ctx 26.4 79.6 Control 3 Parietal Ctx 8.7 7.3 Control
(Path) 1 Parietal 100.0 75.8 Ctx Control (Path) 2 Parietal 9.3 35.6
Ctx Control (Path) 3 Parietal 3.2 9.0 Ctx Control (Path) 4 Parietal
31.2 41.8 Ctx
[0583] TABLE-US-00128 TABLE EC General_screening_panel_v1.4 Rel.
Exp.(%) Rel. Exp.(%) Ag4235, Ag4235, Run Run Tissue Name 221994384
Tissue Name 221994384 Adipose 0.6 Renal ca. TK-10 0.8 Melanoma* 3.4
Bladder 2.7 Hs688(A).T Melanoma* 3.6 Gastric ca. (liver met.) 0.0
Hs688(B).T NCI-N87 Melanoma* M14 0.2 Gastric ca. KATO III 0.0
Melanoma* 0.0 Colon ca. SW-948 0.0 LOXIMVI Melanoma* SK- 0.2 Colon
ca. SW480 0.9 MEL-5 Squamous cell 0.2 Colon ca.* (SW480 0.0
carcinoma SCC-4 met) SW620 Testis Pool 1.1 Colon ca. HT29 0.0
Prostate ca.* (bone 1.5 Colon ca. HCT-116 0.1 met) PC-3 Prostate
Pool 6.2 Colon ca. CaCo-2 0.0 Placenta 0.4 Colon cancer tissue 3.4
Uterus Pool 0.0 Colon ca. SW1116 100.0 Ovarian ca. 0.1 Colon ca.
Colo-205 0.0 OVCAR-3 Ovarian ca. SK- 0.1 Colon ca. SW-48 0.0 OV-3
Ovarian ca. 0.0 Colon Pool 0.4 OVCAR-4 Ovarian ca. 0.9 Small
Intestine Pool 0.6 OVCAR-5 Ovarian ca. 3.4 Stomach Pool 0.3 IGROV-1
Ovarian ca. 5.1 Bone Marrow Pool 0.0 OVCAR-8 Ovary 0.2 Fetal Heart
0.0 Breast ca. MCF-7 0.0 Heart Pool 0.3 Breast ca. MDA- 6.1 Lymph
Node Pool 0.6 MB-231 Breast ca. BT 549 0.0 Fetal Skeletal Muscle
0.2 Breast ca. T47D 1.7 Skeletal Muscle Pool 0.4 Breast ca. MDA-N
0.0 Spleen Pool 2.7 Breast Pool 0.2 Thymus Pool 0.7 Trachea 1.1 CNS
cancer 6.4 (glio/astro) U87-MG Lung 0.2 CNS cancer 2.1 (glio/astro)
U-118-MG Fetal Lung 0.6 CNS cancer 0.2 (neuro; met) SK-N-AS Lung
ca. NCI-N417 1.3 CNS cancer (astro) 2.4 SF-539 Lung ca. LX-1 0.0
CNS cancer (astro) 2.9 SNB-75 Lung ca. NCI-H146 0.4 CNS cancer
(glio) 4.1 SNB-19 Lung ca. SHP-77 2.7 CNS cancer (glio) SF- 14.2
295 Lung ca. A549 1.4 Brain (Amygdala) 55.5 Pool Lung ca. NCI-H526
3.2 Brain (cerebellum) 10.6 Lung ca. NCI-H23 3.3 Brain (fetal) 21.2
Lung ca. NCI-H460 17.4 Brain (Hippocampus) 20.7 Pool Lung ca.
HOP-62 5.1 Cerebral Cortex Pool 14.4 Lung ca. NCI-H522 3.2 Brain
(Substantia 47.0 nigra) Pool Liver 0.0 Brain (Thalamus) Pool 36.1
Fetal Liver 0.0 Brain (whole) 18.9 Liver ca. HepG2 0.0 Spinal Cord
Pool 18.8 Kidney Pool 0.2 Adrenal Gland 0.8 Fetal Kidney 0.5
Pituitary gland Pool 0.0 Renal ca. 786-0 2.0 Salivary Gland 0.2
Renal ca. A498 0.4 Thyroid (female) 0.0 Renal ca. ACHN 0.3
Pancreatic ca. 0.0 CAPAN2 Renal ca. UO-31 0.0 Pancreas Pool 0.5
[0584] TABLE-US-00129 TABLE ED Panel 4.1D Rel. Exp.(%) Rel. Exp.(%)
Ag4235, Run Ag4235, Run Tissue Name 175226633 Tissue Name 175226633
Secondary Th1 act 3.0 HUVEC IL-1beta 0.0 Secondary Th2 act 9.9
HUVEC IFN gamma 0.0 Secondary Tr1 act 3.8 HUVEC TNF alpha + IFN 0.0
gamma Secondary Th1 rest 16.0 HUVEC TNF alpha + IL4 0.0 Secondary
Th2 rest 21.3 HUVEC IL-11 0.0 Secondary Tr1 rest 18.2 Lung
Microvascular EC 0.0 none Primary Th1 act 0.0 Lung Microvascular EC
0.0 TNF alpha + IL-1beta Primary Th2 act 5.4 Microvascular Dermal
0.0 EC none Primary Tr1 act 0.0 Microsvasular Dermal 6.0 EC TNF
alpha + IL-1beta Primary Th1 rest 1.9 Bronchial epithelium 0.0 TNF
alpha + IL1beta Primary Th2 rest 1.6 Small airway epithelium 2.9
none Primary Tr1 rest 5.5 Small airway epithelium 0.0 TNF alpha +
IL-1beta CD45RA CD4 1.2 Coronery artery SMC 0.0 lymphocyte act rest
CD45RO CD4 0.0 Coronery artery SMC 2.1 lymphocyte act TNF alpha +
IL-1beta CD8 lymphocyte act 5.8 Astrocytes rest 5.5 Secondary CD8
3.0 Astrocytes TNF alpha + IL- 13.6 lymphocyte rest 1beta Secondary
CD8 26.2 KU-812 (Basophil) rest 0.0 lymphocyte act CD4 lymphocyte
none 3.8 KU-812 (Basophil) 0.0 PMA/ionomycin 2ry Th1/Th2/Tr1_anti-
24.1 CCD1106 0.0 CD95 CH11 (Keratinocytes) none LAK cells rest 0.0
CCD1106 1.3 (Keratinocytes) TNF alpha + IL-1beta LAK cells IL-2
19.8 Liver cirrhosis 0.0 LAK cells IL-2 + IL-12 0.0 NCI-H292 none
1.2 LAK cells IL-2 + IFN 10.2 NCI-H292 IL-4 0.0 gamma LAK cells
IL-2 + IL-18 1.5 NCI-H292 IL-9 0.8 LAK cells 1.3 NCI-H292 IL-13 0.0
PMA/ionomycin NK Cells IL-2 rest 13.3 NCI-H292 IFN gamma 0.0 Two
Way MLR 3 day 3.5 HPAEC none 0.0 Two Way MLR 5 day 2.0 HPAEC TNF
alpha + IL- 0.0 1beta Two Way MLR 7 day 3.3 Lung fibroblast none
1.9 PBMC rest 18.8 Lung fibroblast TNF 17.7 alpha + IL-1beta PBMC
PWM 4.9 Lung fibroblast IL-4 3.3 PBMC PHA-L 1.4 Lung fibroblast
IL-9 3.9 Ramos (B cell) none 0.0 Lung fibroblast IL-13 4.8 Ramos (B
cell) 0.0 Lung fibroblast IFN 2.6 ionomycin gamma B lymphocytes PWM
0.0 Dermal fibroblast 1.3 CCD1070 rest B lymphocytes CD40L 1.9
Dermal fibroblast 2.7 and IL-4 CCD1070 TNF alpha EOL-1 dbcAMP 15.4
Dermal fibroblast 0.0 CCD1070 IL-1beta EOL-1 dbcAMP 18.8 Dermal
fibroblast IFN 0.5 PMA/ionomycin gamma Dendritic cells none 0.0
Dermal fibroblast IL-4 3.8 Dendritic cells LPS 0.0 Dermal
Fibroblasts rest 0.0 Dendritic cells anti- 0.0 Neutrophils TNFa +
LPS 28.9 CD40 Monocytes rest 12.9 Neutrophils rest 56.3 Monocytes
LPS 0.0 Colon 5.4 Macrophages rest 5.1 Lung 10.9 Macrophages LPS
1.6 Thymus 27.0 HUVEC none 0.0 Kidney 100.0 HUVEC starved 0.0
[0585] TABLE-US-00130 TABLE EE Panel CNS_1 Rel. Exp.(%) Rel.
Exp.(%) Ag4235, Ag4235, Run Run Tissue Name 181012601 Tissue Name
181012601 BA4 Control 7.1 BA17 PSP 10.3 BA4 Control2 17.3 BA17 PSP2
3.6 BA4 7.0 Sub Nigra Control 11.7 Alzheimer's2 BA4 Parkinson's
16.3 Sub Nigra Control2 7.5 BA4 64.2 Sub Nigra 4.3 Parkinson's2
Alzheimer's2 BA4 13.2 Sub Nigra 22.7 Huntington's Parkinson's2 BA4
8.2 Sub Nigra 43.5 Huntington's2 Huntington's BA4 PSP 7.1 Sub Nigra
6.5 Huntington's2 BA4 PSP2 9.0 Sub Nigra PSP2 5.6 BA4 Depression
100.0 Sub Nigra 2.7 Depression BA4 5.8 Sub Nigra 0.8 Depression2
Depression2 BA7 Control 12.2 Glob Palladus 7.6 Control BA7 Control2
22.8 Glob Palladus 6.9 Control2 BA7 3.5 Glob Palladus 4.5
Alzheimer's2 Alzheimer's BA7 Parkinson's 17.7 Glob Palladus 7.8
Alzheimer's2 BA7 27.7 Glob Palladus 54.0 Parkinson's2 Parkinson's
BA7 21.6 Glob Palladus 5.5 Huntington's Parkinson's2 BA7 22.2 Glob
Palladus PSP 5.4 Huntington's2 BA7 PSP 9.2 Glob Palladus PSP2 3.4
BA7 PSP2 6.7 Glob Palladus 0.5 Depression BA7 Depression 5.2 Temp
Pole Control 8.5 BA9 Control 7.6 Temp Pole Control2 27.0 BA9
Control2 29.1 Temp Pole 4.6 Alzheimer's BA9 9.4 Temp Pole 5.6
Alzheimer's Alzheimer's2 BA9 4.5 Temp Pole 15.4 Alzheimer's2
Parkinson's BA9 Parkinson's 21.5 Temp Pole 24.0 Parkinson's2 BA9
17.1 Temp Pole 21.5 Parkinson's2 Huntington's BA9 14.1 Temp Pole
PSP 4.0 Huntington's BA9 15.9 Temp Pole PSP2 3.9 Huntington's2 BA9
PSP 7.3 Temp Pole 13.8 Depression2 BA9 PSP2 2.2 Cing Gyr Control
15.6 BA9 Depression 5.5 Cing Gyr Control2 14.9 BA9 4.7 Cing Gyr 5.6
Depression2 Alzheimer's BA17 Control 15.7 Cing Gyr 6.6 Alzheimer's2
BA17 Control2 18.0 Cing Gyr 18.7 Parkinson's BA17 5.9 Cing Gyr 20.9
Alzheimer's2 Parkinson's2 BA17 25.9 Cing Gyr 30.4 Parkinson's
Huntington's BA17 24.0 Cing Gyr 8.0 Parkinson's2 Huntington's2 BA17
17.4 Cing Gyr PSP 6.3 Huntington's BA17 14.6 Cing Gyr PSP2 0.4
Huntington's2 BA17 8.9 Cing Gyr 5.8 Depression Depression BA17 15.8
Cing Gyr 10.1 Depression2 Depression2
[0586] TABLE-US-00131 TABLE EF general oncology screening
panel_v_2.4 Rel. Exp.(%) Rel. Exp.(%) Ag4235, Ag4235, Run Run
Tissue Name 268624980 Tissue Name 268624980 Colon cancer 1 13.6
Bladder cancer NAT 2 0.0 Colon NAT 1 4.0 Bladder cancer NAT 3 0.0
Colon cancer 2 5.7 Bladder cancer NAT 4 12.1 Colon cancer 0.0
Adenocarcinoma of the 13.4 NAT 2 prostate 1 Colon cancer 3 4.1
Adenocarcinoma of the 29.7 prostate 2 Colon cancer 4.5
Adenocarcinoma of the 96.6 NAT 3 prostate 3 Colon malignant 9.0
Adenocarcinoma of the 5.8 cancer 4 prostate 4 Colon normal 0.0
Prostate cancer NAT 5 5.2 adjacent tissue 4 Lung cancer 1 12.4
Adenocarcinoma of the 13.2 prostate 6 Lung NAT 1 7.5 Adenocarcinoma
of the 41.8 prostate 7 Lung cancer 2 3.3 Adenocarcinoma of the 12.2
prostate 8 Lung NAT 2 18.6 Adenocarcinoma of the 27.9 prostate 9
Squamous cell 9.1 Prostate cancer NAT 5.6 carcinoma 3 10 Lung NAT 3
0.0 Kidney, cancer 1 13.8 metastatic 2.3 KidneyNAT 1 7.3 Melanoma 1
Melanoma 2 0.0 Kidney cancer 2 100.0 Melanoma 3 0.0 Kidney NAT 2
9.0 metastatic 10.7 Kidney cancer 3 18.6 melanoma 4 metastatic 8.1
Kidney NAT 3 0.0 melanoma 5 Bladder cancer 1 0.0 Kidney cancer 4
52.9 Bladder cancer 0.0 Kidney NAT 4 0.0 NAT 1 Bladder cancer 2
9.5
[0587] CNS_neurodegeneration_v1.0 Summary: Ag4235 Two experiments
with same probe and primer sets are in excellent agreements. These
results confirm the expression of the NOV7A gene at moderate to low
levels in the brain in an independent group of individuals. This
gene is downregulated in the temporal cortex of Alzheimer's disease
patients when compared with non-demented controls (p=0.0024; p=0.01
when analyzed by Ancova, estimate of total cDNA loaded per well
used asa covariate). Thus, therapeutic modulation of this gene or
its protein product, may be of use in reversing the dementia,
memory loss, and neuronal death associated with this disease.
[0588] General_screening_panel_v1.4 Summary: Ag4235 Highest
expression of the NOV7A gene is seen in a colon cancer cell line
(CT=28.6). Moderate levels of expression are also seen in cell
lines derived from brain cancer, lung cancer, ovarian cancer,
breast cancer, and melanoma. Thus, expression of this gene could be
used to differentiate between this sample and other samples on this
panel and as a marker to detect the presence of colon cancer.
Furthermore, therapeutic modulation of the expression or function
of this gene may be effective in the treatment of colon, brain,
lung, ovarian, breast and melanoma cancers.
[0589] This gene is prominently expressed at high to moderate
levels in all regions of the CNS examined, including the
hippocampus, thalamus, substantia nigra, amygdala, cerebellum and
cerebral cortex. This gene encodes a protein with homology to
netrins, a family of soluble chemotropic factors that have been
implicated in axon guidance and neuron survival during development.
(Llambi F. EMBO J. 20 (11):2715-22; Braisted J E, J. Neurosci.
20:5792-801) Netrin may be involved in the regenerative capacity of
adult retinal ganglion cells (Ellezam B. Exp Neurol 168 (1):105-15)
Therefore, therapeutic modulation of the expression or function of
this gene product may be of use in enhancing or directing
compensatory synatogenesis and axon/dendritic outgrowth in response
to neuronal death (stroke, head trauma) neurodegeneration
(Alzheiemr's, Parkinson's, Huntington's, spinocerebellar ataxia,
progressive supranuclear palsy) or spinal cord injury.
[0590] Among tissues with metabolic function, this gene is
expressed at low but significant levels in adipose, adrenal gland,
pancreas, and skeletal muscle. This expression suggests that this
gene product may play a role in normal neuroendocrine and metabolic
function and that disregulated expression of this gene may
contribute to neuroendocrine disorders or metabolic diseases, such
as obesity and diabetes.
[0591] Panel 4.1D Summary: Ag4235 Highest expression of the NOV7A
gene is seen in the kidney (CT=31.3). Low but significant levels of
expression of this gene are also seen in other samples, including
resting and activated neutrophils and eosinophils, TNF-alpha and
IL-1 beta activated lung fibroblasts and astrocytes, resting PBMCs,
monocytes, and chronically stimulated T cells, and normal thymus
and lung. This expression profile suggests that this gene product
may be involved in kidney function and in the treatment of
inflammatory or autoimmune diseases that affect the kidney,
including lupus and glomerulonephritis.
[0592] Panel CNS.sub.--1 Summary: Ag4235 This panel confirms the
presence of the CG102221-021 gene in the brain, with highest
expression in Brodman Area 4 of a patient with depression
(CT=30.4). Please see Panel 1.4 for discussion of utility of this
gene in the central nervous system.
[0593] general oncology screening panel_v.sub.--2.4 Summary: Ag4235
Highest expression of the NOV7A gene is seen in kidney cancer
(CT=33.8). Thus, expression of this gene could be used to
differentiate between this sample and other samples on this panel
and as a marker to detect the presence of kidney cancer. This gene
is also expressed at a low level in prostate cancer compared to
normal prostate.
[0594] It may be used as a diagnostic marker of kidney and prostate
cancer and therapeutic modulation of the activity of the protein
may be useful in the treatment of these cancers.
[0595] F. NOV8A: Secreted Reprolysin
[0596] Expression of gene NOV8A was assessed using the primer-probe
set Ag4236, described in Table FA. Results of the RTQ-PCR runs are
shown in Tables FB, FC, FD and FE. TABLE-US-00132 TABLE FA Probe
Name Ag4236 Start SEQ ID Primers Sequences Length Position No
Forward 5'-ggcagggatgaaactgtca-3' 19 775 142 Probe
TET-5'-ccttggccccaatgtagagaacactg-3'- 26 812 143 TAMRA Reverse
5'-ctcccgtgacatacactttgac-3' 22 853 144
[0597] TABLE-US-00133 TABLE FB General_screening_panel_v1.4 Rel.
Exp.(%) Rel. Exp.(%) Ag4236, Ag4236, Run Run Tissue Name 222100995
Tissue Name 222100995 Adipose 13.7 Renal ca. TK-10 0.0 Melanoma*
0.0 Bladder 21.2 Hs688(A).T Melanoma* 0.0 Gastric ca. (liver met.)
0.0 Hs688(B).T NCI-N87 Melanoma* M14 43.8 Gastric ca. KATO III 44.1
Melanoma* 0.0 Colon ca. SW-948 12.8 LOXIMVI Melanoma* SK- 0.0 Colon
ca. SW480 100.0 MEL-5 Squamous cell 0.0 Colon ca.* (SW480 11.9
carcinoma SCC-4 met) SW620 Testis Pool 0.0 Colon ca. HT29 0.0
Prostate ca.* (bone 19.2 Colon ca. HCT-116 18.2 met) PC-3 Prostate
Pool 0.0 Colon ca. CaCo-2 0.0 Placenta 0.0 Colon cancer tissue 0.0
Uterus Pool 0.0 Colon ca. SW1116 0.0 Ovarian ca. 0.0 Colon ca.
Colo-205 37.4 OVCAR-3 Ovarian ca. SK- 40.3 Colon ca. SW-48 3.3 OV-3
Ovarian ca. 4.3 Colon Pool 0.0 OVCAR-4 Ovarian ca. 12.2 Small
Intestine Pool 11.6 OVCAR-5 Ovarian ca. 0.0 Stomach Pool 0.0
IGROV-1 Ovarian ca. 0.0 Bone Marrow Pool 7.8 OVCAR-8 Ovary 5.6
Fetal Heart 0.0 Breast ca. MCF-7 12.7 Heart Pool 0.0 Breast ca.
MDA- 0.0 LymPh Node Pool 11.3 MB-231 Breast ca. BT 549 3.8 Fetal
Skeletal Muscle 5.1 Breast ca. T47D 12.9 Skeletal Muscle Pool 29.3
Breast ca. MDA-N 0.0 Spleen Pool 0.0 Breast Pool 9.2 Thymus Pool
20.6 Trachea 11.3 CNS cancer 0.0 (glio/astro) U87-MG Lung 0.0 CNS
cancer 0.0 (glio/astro) U-118-MG Fetal Lung 15.3 CNS cancer 7.9
(neuro; met) SK-N-AS Lung ca. NCI-N417 0.0 CNS cancer (astro) 0.0
SF-539 Lung ca. LX-1 13.3 CNS cancer (astro) 0.0 SNB-75 Lung ca.
NCI-H146 42.6 CNS cancer (glio) 0.0 SNB-19 Lung ca. SHP-77 0.0 CNS
cancer (glio) 0.0 SF-295 Lung ca. A549 0.0 Brain (Amygdala) 0.0
Pool Lung ca. NCI-H526 0.0 Brain (cerebellum) 0.0 Lung ca. NCI-H23
0.0 Brain (fetal) 7.3 Lung ca. NCI-H460 0.0 Brain (Hippocampus) 0.0
Pool Lung ca. HOP-62 0.0 Cerebral Cortex Pool 0.0 Lung ca. NCI-H522
0.0 Brain (Substantia 5.4 nigra) Pool Liver 0.0 Brain (Thalamus)
Pool 9.5 Fetal Liver 0.0 Brain (whole) 0.0 Liver ca. HepG2 0.0
Spinal Cord Pool 11.1 Kidney Pool 22.2 Adrenal Gland 5.8 Fetal
Kidney 0.0 Pituitary gland Pool 0.0 Renal ca. 786-0 0.0 Salivary
Gland 12.2 Renal ca. A498 0.0 Thyroid (female) 0.0 Renal ca. ACHN
2.1 Pancreatic ca. 0.0 CAPAN2 Renal ca. UO-31 0.0 Pancreas Pool
12.3
[0598] TABLE-US-00134 TABLE FC General_screening_panel_v1.6 Rel.
Exp.(%) Rel. Ag4236, Run Exp.(%) Ag4236, Run Tissue Name 277231326
Tissue Name 277231326 Adipose 11.5 Renal ca. TK-10 0.0 Melanoma*
0.0 Bladder 10.1 Hs688(A).T Melanoma* 0.0 Gastric ca. (liver met.)
0.0 Hs688(B).T NCI-N87 Melanoma* M14 30.8 Gastric ca. KATO III 50.0
Melanoma* 0.0 Colon ca. SW-948 0.0 LOXIMVI Melanoma* SK- 39.0 Colon
ca. SW480 100.0 MEL-5 Squamous cell 0.0 Colon ca.* (SW480 18.6
carcinoma SCC-4 met) SW620 Testis Pool 0.0 Colon ca. HT29 10.3
Prostate ca.* (bone 45.4 Colon ca. HCT-116 27.0 met) PC-3 Prostate
Pool 5.5 Colon ca. CaCo-2 0.0 Placenta 0.0 Colon cancer tissue 3.0
Uterus Pool 0.0 Colon ca. SW1116 0.0 Ovarian ca. 0.0 Colon ca.
Colo-205 20.9 OVCAR-3 Ovarian ca. SK- 41.8 Colon ca. SW-48 0.0 OV-3
Ovarian ca. 5.9 Colon Pool 6.0 OVCAR-4 Ovarian ca. 26.8 Small
Intestine Pool 9.6 OVCAR-5 Ovarian ca. 0.0 Stomach Pool 24.7
IGROV-1 Ovarian ca. 0.0 Bone Marrow Pool 5.5 OVCAR-8 Ovary 21.6
Fetal Heart 0.0 Breast ca. MCF-7 5.8 Heart Pool 8.6 Breast ca. MDA-
10.1 Lymph Node Pool 7.2 MB-231 Breast ca. BT 549 0.0 Fetal
Skeletal Muscle 0.0 Breast ca. T47D 0.0 Skeletal Muscle Pool 20.9
Breast ca. MDA-N 0.0 Spleen Pool 12.4 Breast Pool 9.0 Thymus Pool
21.0 Trachea 2.9 CNS cancer 0.0 (glio/astro) U87-MG Lung 0.0 CNS
cancer 0.0 (glio/astro) U-118-MG Fetal Lung 17.2 CNS cancer 5.9
(neuro; met) SK-N-AS Lung ca. NCI-N417 0.0 CNS cancer (astro) SF-
0.0 539 Lung ca. LX-1 17.3 CNS cancer (astro) 0.0 SNB-75 Lung ca.
NCI-H146 14.7 CNS cancer (glio) 3.9 SNB-19 Lung ca. SHP-77 0.0 CNS
cancer (glio) SF- 0.0 295 Lung ca. A549 10.7 Brain (Amygdala) 0.0
Pool Lung ca. NCI-H526 4.4 Brain (cerebellum) 9.9 Lung ca. NCI-H23
0.0 Brain (fetal) 7.0 Lung ca. NCI-H460 7.2 Brain (Hippocampus) 0.0
Pool Lung ca. HOP-62 0.0 Cerebral Cortex Pool 0.0 Lung ca. NCI-H522
0.0 Brain (Substantia 6.2 nigra) Pool Liver 0.0 Brain (Thalamus)
Pool 4.6 Fetal Liver 0.0 Brain (whole) 9.7 Liver ca. HepG2 0.0
Spinal Cord Pool 3.9 Kidney Pool 6.2 Adrenal Gland 5.4 Fetal Kidney
5.6 Pituitary gland Pool 0.0 Renal ca. 786-0 0.0 Salivary Gland 5.3
Renal ca. A498 0.0 Thyroid (female) 0.0 Renal ca. ACHN 0.0
Pancreatic ca. 0.0 CAPAN2 Renal ca. UO-31 0.0 Pancreas Pool
18.6
[0599] TABLE-US-00135 TABLE FD Panel 4.1D Rel. Exp.(%) Rel. Exp.(%)
Ag4236, Run Ag4236, Run Tissue Name 175226753 Tissue Name 175226753
Secondary Th1 act 0.0 HUVEC IL-1beta 0.0 Secondary Th2 act 0.0
HUVEC IFN gamma 0.0 Secondary Tr1 act 0.0 HUVEC TNF alpha + IFN 0.0
gamma Secondary Th1 rest 5.3 HUVEC TNF alpha + IL4 0.0 Secondary
Th2 rest 0.0 HUVEC IL-11 0.0 Secondary Tr1 rest 0.0 Lung
Microvascular EC 0.0 none Primary Th1 act 1.0 Lung Microvascular EC
0.0 TNF alpha + IL-1beta Primary Th2 act 2.8 Microsvasular Dermal
0.0 EC none Primary Tr1 act 1.2 Microsvasular Dermal 0.9 EC TNF
alpha + IL-1beta Primary Th1 rest 1.4 Bronchial epithelium 0.0 TNF
alpha + IL1beta Primary Th2 rest 4.0 Small airway epithelium 0.0
none Primary Tr1 rest 12.5 Small airway epithelium 0.0 TNF alpha +
IL-1beta CD45RA CD4 0.0 Coronery artery SMC 0.0 lymphocyte act rest
CD45RO CD4 0.0 Coronery artery SMC 0.0 lymphocyte act TNF alpha +
IL-1beta CD8 lymphocyte act 0.0 Astrocytes rest 0.0 Secondary CD8
1.9 Astrocytes TNF alpha + IL- 0.0 lymphocyte rest 1beta Secondary
CD8 0.0 KU-812 (Basophil) rest 0.0 lymphocyte act CD4 lymphocyte
none 5.1 KU-812 (Basophil) 0.0 PMA/ionomycin 2ry Th1/Th2/Tr1_anti-
0.0 CCD1106 0.0 CD95 CH11 (Keratinocytes) none LAK cells rest 0.0
CCD1106 0.0 (Keratinocytes) TNF alpha + IL-1beta LAK cells IL-2 0.0
Liver cirrhosis 1.5 LAK cells IL-2 + IL-12 0.0 NCI-H292 none 0.0
LAK cells IL-2 + IFN 1.8 NCI-H292 IL-4 0.0 gamma LAK cells IL-2 +
IL-18 9.2 NCI-H292 IL-9 0.0 LAK cells 0.0 NCI-H292 IL-13 0.0
PMA/ionomycin NK Cells IL-2 rest 2.5 NCI-H292 IFN gamma 3.3 Two Way
MLR 3 day 1.9 HPAEC none 0.0 Two Way MLR 5 day 0.0 HPAEC TNF alpha
+ IL- 0.0 1beta Two Way MLR 7 day 0.0 Lung fibroblast none 0.0 PBMC
rest 4.3 Lung fibroblast TNF 0.0 alpha + IL-1beta PBMC PWM 2.3 Lung
fibroblast IL-4 0.0 PBMC PHA-L 0.0 Lung fibroblast IL-9 0.0 Ramos
(B cell) none 0.0 Lung fibroblast IL-13 3.4 Ramos (B cell) 0.0 Lung
fibroblast IFN 2.1 ionomycin gamma B lymphocytes PWM 0.0 Dermal
fibroblast 0.0 CCD1070 rest B lymphocytes CD40L 0.0 Dermal
fibroblast 0.0 and IL-4 CCD1070 TNF alpha EOL-1 dbcAMP 0.0 Dermal
fibroblast 0.0 CCD1070 IL-1beta EOL-1 dbcAMP 0.0 Dermal fibroblast
IFN 0.0 PMA/ionomycin gamma Dendritic cells non 0.0 Dermal
fibroblast IL-4 0.0 Dendritic cells LPS 0.0 Dermal Fibroblasts rest
0.0 Dendritic cells anti- 0.0 Neutrophils TNFa + LPS 0.0 CD40
Monocytes rest 0.0 Neutrophils rest 3.0 Monocytes LPS 0.0 Colon 0.8
Macrophages rest 0.0 Lung 1.1 Macrophages LPS 0.0 Thymus 20.9 HUVEC
none 0.0 Kidney 100.0 HUVEC starved 0.0
[0600] TABLE-US-00136 TABLE FE general oncology screening
panel_v_2.4 Rel. Exp.(%) Rel. Exp.(%) Ag4236, Ag4236, Run Run
Tissue Name 268664312 Tissue Name 268664312 Colon cancer 1 44.4
Bladder cancer NAT 2 0.0 Colon cancer 0.0 Bladder cancer NAT 3 0.0
NAT 1 Colon cancer 2 0.0 Bladder cancer NAT 4 0.0 Colon cancer 0.0
Adenocarcinoma of the 34.6 NAT 2 prostate 1 Colon cancer 3 0.0
Adenocarcinoma of the 0.0 prostate 2 Colon cancer 0.0
Adenocarcinoma of the 0.0 NAT 3 prostate 3 Colon malignant 0.0
Adenocarcinoma of the 0.0 cancer 4 prostate 4 Colon normal 0.0
Prostate cancer NAT 5 20.6 adjacent tissue 4 Lung cancer 1 9.0
Adenocarcinoma of the 0.0 prostate 6 Lung NAT 1 0.0 Adenocarcinoma
of the 0.0 prostate 7 Lung cancer 2 39.0 Adenocarcinoma of the 0.0
prostate 8 Lung NAT 2 19.2 Adenocarcinoma of the 0.0 prostate 9
Squamous cell 0.0 Prostate cancer NAT 0.0 carcinoma 3 10 Lung NAT 3
17.2 Kidney cancer 1 0.0 metastatic 0.0 KidneyNAT 1 0.0 melanoma 1
Melanoma 2 30.8 Kidney cancer 2 100.0 Melanoma 3 24.5 Kidney NAT 2
61.1 metastatic 17.3 Kidney cancer 3 0.0 melanoma 4 metastatic 48.0
Kidney NAT 3 0.0 melanoma 5 Bladder cancer 1 0.0 Kidney cancer 4
0.0 Bladder cancer 0.0 Kidney NAT 4 9.9 NAT 1 Bladder cancer 2
0.0
[0601] CNS_neurodegeneration_v1.0 Summary: Ag4236 Expression of the
NOV8A gene is low/undetectable (CTs>35) across all of the
samples on this panel (data not shown).
[0602] General_screening_panel_v1.4 Summary: Ag4236 Highest
expression of the NOV8A gene is detected in a colon cancer SW480
cell line (CT=33). In addition, low expression of this gene is also
seen in a number of cancer cell lines including colon, gastric,
lung, ovarian and melanoma cancer cell lines. Therefore, expression
of this gene can be used as diagnostic markers for these cancers
and also, therapeutic modulation of this gene product may be
beneficial in the treatment of these cancers.
[0603] Low expression of this gene is also seen in skeletal muscle.
Therefore, therapeutic modulation of this gene may be useful in the
treatment of muscle related diseases.
[0604] General_screening_panel_v1.6 Summary: Ag4236 Highest
expression of the NOV8A gene is detected in a colon cancer cell
line (CT=33), in agreement with results in Panel 1.4. In addition,
low but significant levels of expression are seen in melanoma,
prostate, ovarian and gastric cancer cell lines. Therefore,
expression of this gene may be useful as diagnostic marker for
colon cancer and therapeutic modulation of this gene product may be
beneficial in the treatment of these cancers.
[0605] Panel 4.1D Summary: Ag4236 Highest expression of the NOV8A
gene is detected in kidney. Therefore, expression of this gene can
be used to distinguish kidney sample from other samples used in
this panel. In addition, low expression of this gene is also seen
in thymus and resting primary Tr1 cells. Therefore, therapeutic
modulation of this gene product may be useful in the treatment of
autoimmune and inflammatory diseases that affect kidney including
lupus and glomerulonephritis. Expression of this gene in a second
experiment (run 268719696) is low/undetectable (CTs>35) across
all of the samples on this panel (data not shown).
[0606] General oncology screening panel_v.sub.--2.4 Summary: Ag4236
Highest expression of the NOV8A gene is detected in kidney cancer
sample (CT=34.7). Therefore, expression of this gene may be useful
as diagnostic marker and therapeutic modulation of this gene
product may be beneficial in the treatment of kidney cancer.
[0607] G. NOV9A and NOV9B: Ig-domain Containing Transmembrane
Protein
[0608] Expression of gene NOV9A and variant NOV9B was assessed
using the primer-probe sets Ag4244 and Ag4324, described in Tables
GA and GB. Please note that NOV9A is recognized by primer-probe set
Ag4244 only. Results of the RTQ-PCR runs are shown in Tables GC and
GD. TABLE-US-00137 TABLE GA Probe Name Ag4244 Start SEQ ID Primers
Srquences Length Position No Forward 5'-catggagactcccctttgac-3' 20
998 145 Probe TET-5'-cctgaaggaggtcaccatctcattga-3'- 26 1023 146
TAMRA Reverse 5'-cggatcttggacttcaatctc-3' 21 1063 147
[0609] TABLE-US-00138 TABLE GB Probe Name Ag4324 Start SEQ ID
Primers Sequences Length Position No Forward
5'-tgggacaaagaaagagaccaa-3' 21 1149 148 Probe
TET-5'-ttgctgacgcctgtgatcctcact-3' 24 1302 149 TAMRA Reverse
5'-caagggctgagtggagaag-3' 19 1344 150
[0610] TABLE-US-00139 TABLE GC General_screening_panel_v1.4 Rel.
Exp.(%) Ag4244, Run Rel. Exp.(%) Ag4244, Run Tissue Name 222018688
Tissue Name 222018688 Adipose 3.2 Renal ca. TK-10 0.2 Melanoma* 0.0
Bladder 3.2 Hs688(A).T Melanoma* 0.0 Gastric ca. (liver met.) 0.0
Hs688(B).T NCI-N87 Melanoma* M14 0.0 Gastric ca. KATO III 0.0
Melanoma* 0.0 Colon ca. SW-948 0.0 LOXIMVI Melanoma* SK- 0.0 Colon
ca. SW480 0.0 MEL-5 Squamous cell 0.0 Colon ca.* (SW480 0.0
carcinoma SCC-4 met) SW620 Testis Pool 10.2 Colon ca. HT29 0.0
Prostate ca.* (bone 0.0 Colon ca. HCT-116 0.0 met) PC-3 Prostate
Pool 7.5 Colon ca. CaCo-2 0.0 Placenta 1.5 Colon cancer tissue 3.4
Uterus Pool 10.8 Colon ca. SW1116 0.0 Ovarian ca. 0.0 Colon ca.
Colo-205 0.0 OVCAR-3 Ovarian ca. SK- 0.1 Colon ca. SW-48 0.0 OV-3
Ovarian ca. 0.0 Colon Pool 39.8 OVCAR-4 Ovarian ca. 0.0 Small
Intestine Pool 38.7 OVCAR-5 Ovarian ca. 0.2 Stomach Pool 18.2
IGROV-1 Ovarian ca. 0.6 Bone Marrow Pool 22.8 OVCAR-8 Ovary 2.1
Fetal Heart 6.9 Breast ca. MCF-7 0.1 Heart Pool 22.4 Breast ca.
MDA- 0.0 Lymph Node Pool 55.5 MB-231 Breast ca. BT 549 0.0 Fetal
Skeletal Muscle 29.1 Breast ca. T47D 0.0 Skeletal Muscle Pool 44.8
Breast ca. MDA-N 0.0 Spleen Pool 0.7 Breast Pool 29.5 Thymus Pool
18.6 Trachea 7.3 CNS cancer 0.0 (glio/astro) U87-MG Lung 6.5 CNS
cancer 0.8 (glio/astro) U-118-MG Fetal Lung 26.2 CNS cancer 10.7
(neuro; met) SK-N-AS Lung ca. NCI-N417 0.0 CNS cancer (astro) SF-
0.0 539 Lung ca. LX-1 0.0 CNS cancer (astro) 0.7 SNB-75 Lung ca.
NCI-H146 0.9 CNS cancer (glio) 0.0 SNB-19 Lung ca. SHP-77 0.6 CNS
cancer (glio) SF- 0.0 295 Lung ca. A549 0.0 Brain (Amygdala) 0.2
Pool Lung ca. NCI-H526 0.0 Brain (cerebellum) 0.4 Lung ca. NCI-H23
0.0 Brain (fetal) 1.0 Lung ca. NCI-H460 0.0 Brain (Hippocampus) 0.3
Pool Lung ca. HOP-62 0.0 Cerebral Cortex Pool 0.1 Lung ca. NCI-H522
0.0 Brain (Substantia 0.2 nigra) Pool Liver 0.3 Brain (Thalamus)
Pool 0.4 Fetal Liver 2.6 Brain (whole) 0.7 Liver ca. HepG2 0.0
Spinal Cord Pool 0.6 Kidney Pool 100.0 Adrenal Gland 2.3 Fetal
Kidney 2.5 Pituitary gland Pool 0.7 Renal ca. 786-0 0.1 Salivary
Gland 0.9 Renal ca. A498 0.2 Thyroid (female) 3.1 Renal ca. ACHN
0.2 Pancreatic ca. 0.0 CAPAN2 Renal ca. UO-31 0.0 Pancreas Pool
58.6
[0611] TABLE-US-00140 TABLE GD General oncology screening
panel_v_2.4 Rel. Exp.(%) Rel. Exp.(%) Ag4244, Ag4244, Run Run
Tissue Name 268664319 Tissue Name 268664319 Colon cancer 1 1.0
Bladder cancer NAT 2 0.0 Colon NAT 1 3.8 Bladder cancer NAT 3 0.0
Colon cancer 2 0.4 Bladder cancer NAT 4 1.0 Colon cancer 1.5
Adenocarcinoma of the 0.1 NAT 2 prostate 1 Colon cancer 3 0.6
Adenocarcinoma of the 0.2 prostate 2 Colon cancer 8.0
Adenocarcinoma of the 0.5 NAT 3 prostate 3 Colon malignant 0.2
Adenocarcinoma of the 0.3 cancer 4 prostate 4 Colon normal 0.5
Prostate cancer NAT 5 1.2 adjacent tissue 4 Lung cancer 1 0.1
Adenocarcinoma of the 0.1 prostate 6 Lung NAT 1 0.1 Adenocarcinoma
of the 0.0 prostate 7 Lung cancer 2 1.8 Adenocarcinoma of the 0.1
prostate 8 Lung NAT 2 1.1 Adenocarcinoma of the 2.8 prostate 9
Squamous cell 0.9 Prostate cancer NAT 0.1 carcinoma 3 10 Lung NAT 3
0.0 Kidney cancer 1 1.4 metastatic 0.8 KidneyNAT 1 0.5 melanoma 1
Melanoma 2 0.4 Kidney cancer 2 2.0 Melanoma 3 0.3 Kidney NAT 2
100.0 metastatic 2.4 Kidney cancer 3 0.4 melanoma 4 metastatic 1.1
Kidney NAT 3 0.6 melanoma 5 Bladder cancer 1 0.1 Kidney cancer 4
0.7 Bladder cancer 0.0 Kidney NAT 4 0.3 NAT 1 Bladder cancer 2
0.1
[0612] CNS_neurodegeneration_v1.0 Summary: Ag4244/Ag4324 Expression
of this gene is low/undetectable in all samples on this panel
(CTs>35). (Data not shown.)
[0613] General_screening_panel_v1.4 Summary: Ag4244 Highest
expression of the NOV9A gene is seen in the kidney (CT=28.3).
Expression in fetal kidney is significantly lower (CT=33). Thus,
expression of this gene could be used to differentiate between
fetal and adult kidney. Overall, this gene appears to be expressed
in normal tissues and may be involved in the normal function of the
kidney.
[0614] Among tissues with metabolic function, this gene is
expressed at moderate to low levels in adipose, adrenal gland,
pancreas, thyroid, fetal liver and adult and fetal skeletal muscle
and heart. This expression among these tissues suggests that this
gene product may play a role in normal neuroendocrine and metabolic
function and that disregulated expression of this gene may
contribute to neuroendocrine disorders or metabolic diseases, such
as obesity and diabetes.
[0615] A second experiment with the probe and primer set Ag4324,
which is specific to NOV9B, shows low/undetectable levels of
expression (CTs>35). (Data not shown.)
[0616] General oncology screening panel_V.sub.--2.4 Summary: Ag4244
Highest expression of the NOV9A gene is seen in the kidney
(CT=26.7). This expression is consistent with expression seen in
the previous panels. Thus, expression of this gene could be used as
a marker of kidney tissue.
[0617] H. NOV10A and NOV10B: Novel Lipocalin 2
[0618] Expression of gene NOV10A and variant NOV10B was assessed
using the primer-probe sets Ag4254 and Ag6132, described in Tables
HA and HB. Results of the RTQ-PCR runs are shown in Tables HC, HD
and HE. Please note that NOV10B represents a full-length physical
clone, validating the prediction of the gene sequence.
TABLE-US-00141 TABLE HA Probe Name Ag4254 Start SEQ ID Primers
Sequences Length Position No Forward 5'cttcatccgcttctccaaat-3' 20
516 151 Probe TET-5'-cctgaaaaccacatcgtcttccctgt-3'- 26 547 152
TAMRA Reverse 5'-ctcatccagactggccattac-3' 21 581 153
[0619] TABLE-US-00142 TABLE HB Probe Name Ag6132 Start SEQ ID
Primers Sequences Length Position No Forward
5'-ggagaacttcatccgcttct-3' 20 510 154 Probe
TET-5'-cctgaaaaccacatcgtcttccctgt-3'- 26 547 155 TAMRA Reverse
5'-ctcatccagactggccattac-3'21 581 156
[0620] TABLE-US-00143 TABLE HC A1_comprehensive panel_v1.0 Rel.
Exp.(%) Ag6132, Run Rel. Exp.(%) Ag6132, Run Tissue Name 255326117
Tissue Name 255326117 110967 COPD-F 1.0 112427 Match Control 0.5
Psoriasis-F 110980 COPD-F 0.0 112418 Psoriasis-M 0.0 110968 COPD-M
0.0 112723 Match Control 0.0 Psoriasis-M 110977 COPD-M 1.9 112419
Psoriasis-M 0.4 110989 Emphysema-F 0.0 112424 Match Control 0.0
Psoriasis-M 110992 Emphysema-F 0.9 112420 Psoriasis-M 1.4 110993
Emphysema-F 0.0 112425 Match Control 0.8 Psoriasis-M 110994
Emphysema-F 0.0 104689 (MF) OA 0.0 Bone-Backus 110995 Emphysema-F
2.8 104690 (MF) Adj 0.0 "Normal" Bone- Backus 110996 Emphysema-F
0.0 104691 (MF) OA 0.0 Synovium-Backus 110997 Asthma-M 4.1 104692
(BA) OA 0.0 Cartilage-Backus 111001 Asthma-F 0.0 104695 (BA) OA 1.8
Bone Backus 111002 Asthma-F 0.8 104695 (BA) Adj 0.0 "Normal" Bone-
Backus 111003 Atopic 0.0 104696 (BA) OA 0.0 Asthma-F
Synovium-Backus 111004 Atopic 1.6 104700 (SS) OA 27.4 Asthma-F
Bone-Backus 111005 Atopic 0.0 104701 (SS) Adj 1.2 Asthma-F "Normal"
Bone- Backus 111006 Atopic 0.0 104702 (SS) OA 1.0 Asthma-F
Synovium-Backus 111417 Allergy-M 0.0 117093 OA Cartilage 0.9 Rep7
112347 Allergy-M 0.3 112672 OA Bone5 0.0 112349 Normal 0.3 112673
OA 0.0 Lung-F Synovium5 112357 Normal 0.0 112674 OA Synovial 0.0
Lung-F Fluid cells5 112354 Normal 0.0 117100 OA Cartilage 0.0
Lung-M Rep14 112374 Crohns-F 0.0 112756 OA Bone9 0.0 112389 Match
100.0 112757 OA 0.0 Control Crohns-F Synovium9 112375 Crohns-F 0.0
112758 OA Synovial 0.0 Fluid Cells9 112732 Match 28.3 117125 RA
Cartilage 0.8 Control Crohns-F Rep2 112725 Crohns-M 0.9 113492
Bone2 RA 9.6 112387 Match 0.0 113493 Synovium2 1.5 Control Crohns-M
RA 112378 Crohns-M 0.4 113494 Syn Fluid 2.4 Cells RA 112390 Match
0.0 113499 Cartilage4 RA 0.0 Control Crohns-M 112726 Crohns-M 0.0
113500 Bone4 RA 0.9 112731 Match 9.0 113501 Synovium4 0.0 Control
Crohns-M RA 112380 Ulcer Col-F 0.0 113502 Syn Fluid 1.0 Cells4 RA
112734 Match 98.6 113495 Cartilage3 RA 0.9 Control Ulcer Col-F
112384 Ulcer Col-F 0.5 113496 Bone3 RA 1.4 112737 Match 0.0 113497
Synovium3 2.3 Control Ulcer Col-F RA 112386 Ulcer Col-F 0.0 113498
Syn Fluid 2.9 Cells3 RA 112738 Match 16.3 117106 Normal 0.0 Control
Ulcer Col-F Cartilage Rep20 112381 Ulcer Col-M 0.0 113663 Bone3
Normal 1.1 112735 Match 0.0 113664 Synovium3 0.0 Control Ulcer
Col-M Normal 112382 Ulcer Col-M 16.4 113665 Syn Fluid 0.0 Cells3
Normal 112394 Match 0.0 117107 Normal 0.0 Control Ulcer Col-M
Cartilage Rep22 112383 Ulcer Col-M 5.1 113667 Bone4 Normal 0.3
112736 Match 30.4 113668 Synovium4 1.2 Control Ulcer Col-M Normal
112423 Psoriasis-F 0.0 113669 Syn Fluid 5.8 Cells4 Normal
[0621] TABLE-US-00144 TABLE HD General_screening_panel_v1.6 Rel.
Exp.(%) Rel. Exp.(%) Ag6132, Ag6132, Run Run Tissue Name 277231849
Tissue Name 277231849 Adipose 0.0 Renal ca. TK-10 3.7 Melanoma* 0.0
Bladder 6.1 Hs688(A).T Melanoma* 0.0 Gastric ca. (liver met.) 100.0
Hs688(B).T NCI-N87 Melanoma* M14 0.0 Gastric ca. KATO III 4.4
Melanoma* 0.0 Colon ca. SW-948 0.2 LOXIMVI Melanoma* SK- 0.0 Colon
ca. SW480 1.0 MEL-5 Squamous cell 3.3 Colon ca.* (SW480 0.1
carcinoma SCC-4 met) SW620 Testis Pool 0.1 Colon ca. HT29 1.7
Prostate ca.* (bone 0.0 Colon ca. HCT-116 0.1 met) PC-3 Prostate
Pool 0.1 Colon ca. CaCo-2 0.0 Placenta 0.0 Colon cancer tissue 30.6
Uterus Pool 0.2 Colon ca. SW1116 0.0 Ovarian ca. 0.2 Colon ca.
Colo-205 0.1 OVCAR-3 Ovarian ca. SK- 0.1 Colon ca. SW-48 0.0 OV-3
Ovarian ca. 0.0 Colon Pool 0.0 OVCAR-4 Ovarian ca. 21.9 Small
Intestine Pool 0.2 Renal ca. ACHN 0.0 Pancreatic ca. 14.9 CAPAN2
Renal ca. UO-31 1.7 Pancreas Pool 1.5
[0622] TABLE-US-00145 TABLE HE Panel 4.1D Rel. Exp.(%) Rel. Exp.(%)
Ag6132, Run Ag6132, Run Tissue Name 254398390 Tissue Name 254398390
Secondary Th1 act 0.0 HUVEC IL-1beta 0.0 Secondary Th2 act 0.0
HUVEC IFN gamma 0.0 Secondary Tr1 act 0.0 HUVEC TNF alpha + IFN 0.0
gamma Secondary Th1 rest 0.0 HUVEC TNF alpha + IL4 0.0 Secondary
Th2 rest 0.0 HUVEC IL-11 0.0 Secondary Tr1 rest 0.0 Lung
Microvascular EC 0.0 none Primary Th1 act 0.0 Lung Microvascular EC
0.0 TNF alpha + IL-1beta Primary Th2 act 0.0 Microvascular Dermal
0.0 EC none Primary Tr1 act 0.0 Microsvasular Dermal 0.0 EC TNF
alpha + IL-1beta Primary Th1 rest 0.0 Bronchial epithelium 5.8 TNF
alpha + IL1beta Primary Th2 rest 0.0 Small airway epithelium 14.2
none Primary Tr1 rest 0.0 Small airway epithelium 100.0 TNF alpha +
IL-1beta CD45RA CD4 0.0 Coronery artery SMC 0.0 lymphocyte act rest
CD45RO CD4 0.0 Coronery artery SMC 0.0 lymphocyte act TNF alpha +
IL-1beta CD8 lymphocyte act 0.0 Astrocytes rest 0.0 Secondary CD8
0.0 Astrocytes TNF alpha + IL- 1.9 lymphocyte rest 1beta Secondary
CD8 0.0 KU-812 (Basophil) rest 0.0 lymphocyte act CD4 lymphocyte
none 0.0 KU-812 (Basophil) 0.0 PMA/ionomycin 2ry Th1/Th2/Tr1_anti-
0.0 CCD1106 0.5 CD95 CH11 (Keratinocytes) none LAK cells rest 0.0
CCD1106 0.0 (Keratinocytes) TNF alpha + IL-1beta LAK cells IL-2 0.0
Liver cirrhosis 3.5 LAK cells IL-2 + IL-12 0.0 NCI-H292 none 23.2
LAK cells IL-2 + IFN 0.0 NCI-H292 IL-4 15.2 gamma LAK cells IL-2 +
IL-18 0.0 NCI-H292 IL-9 29.1 LAK cells 0.0 NCI-H292 IL-13 26.4
PMA/ionomycin NK Cells IL-2 rest 0.0 NCI-H292 IFN gamma 2.9 Two Way
MLR 3 day 0.0 HPAEC none 0.0 Two Way MLR 5 day 0.0 HPAEC TNF alpha
+ IL- 0.0 1beta Two Way MLR 7 day 0.0 Lung fibroblast none 0.0 PBMC
rest 0.0 Lung fibroblast TNF 0.0 alpha + IL-1beta PBMC PWM 0.0 Lung
fibroblast IL-4 0.0 PBMC PHA-L 0.0 Lung fibroblast IL-9 0.0 Ramos
(B cell) none 0.0 Lung fibroblast IL-13 0.0 Ramos (B cell) 0.0 Lung
fibroblast IFN 0.0 ionomycin gamma B lymphocytes PWM 0.0 Dermal
fibroblast 0.0 CCD1070 rest B lymphocytes CD40L 0.0 Dermal
fibroblast 0.0 and IL-4 CCD1070 TNF alpha EOL-1 dbcAMP 0.8 Dermal
fibroblast 0.0 CCD1070 IL-1beta EOL-1 dbcAMP 0.0 Dermal fibroblast
IFN 0.0 PMA/ionomycin gamma Dendritic cells none 0.0 Dermal
fibroblast IL-4 0.0 Dendritic cells LPS 0.0 Dermal Fibroblasts rest
0.0 Dendritic cells anti- 0.0 Neutrophils TNFa + LPS 0.0 CD40
Monocytes rest 0.0 Neutrophils rest 0.0 Monocytes LPS 0.0 Colon 0.0
Macrophages rest 0.0 Lung 0.0 Macrophages LPS 0.0 Thymus 0.0 HUVEC
none 0.0 Kidney 0.4 HUVEC starved 0.0
[0623] AI_comprehensive_panel_v1.0 Summary: Ag6132 Highest
expression of the NOV10A gene is detected in match Crohns and
ulcerative colitis control samples (CTs=30.4). Interestingly,
expression of this gene is higher in the matched control colon
samples as compared to diseased (Crohns and ulcerative colitis)
samples. Low expression of this gene is also seen in synovial
fluid, bone sample from orthoarthritis and rheumatide arthritis
patients. Therefore, therapeutic modulation of this gene may be
beneficial in the treatment of inflammatory bowel diseases and
arthritis.
[0624] The NOV10A gene codes for a variant of neutrophil
gelatinase-associated lipocalin precursor (NGAL). NGAL is a 25-kDa
lipocalin originally purified from human neutrophils. Besides
neutrophils, NGAL is expressed in most tissues normally exposed to
microorganisms, and its synthesis is induced in epithelial cells
during inflammation (Kjeldsen et al., 2000, Biochim Biophys Acta
1482(1-2):272-83, PMID: 11058768). Thus, NGAL may serve an
important anti-inflammatory function as a scavenger of bacterial
products.
[0625] CNS_neurodegeneration_v1.0 Summary: Ag4254 Expression of the
NOV10A gene is low/undetectable (CTs>35) across all of the
samples on this panel (data not shown).
[0626] General_screening_panel_v1.4 Summary: Ag4254 Expression of
the NOV10A gene is low/undetectable (CTs>35) across all of the
samples on this panel (data not shown).
[0627] General_screening_panel_v1.6 Summary: Ag6132 Expression of
this gene appears to be associated with cancer cell lines in this
panel, with highest expression in a gastric cancer cell line
(CT=26.3). Moderate levels of expression are also seen in cell
lines derived from pancreatic, colon, ovarian and squamous cell
cancers. Thus, expression of this gene could be used to
differentiate between the gastric cancer cell line and other
samples on this panel and as a marker of gastric cancer.
Furthermore, therapeutic modulation of the expression or function
of this protein may be effective in the treatment of gastric,
pancreatic, colon, ovarian and squamous cell cancers.
[0628] Panel 4.1D Summary: Ag6132 Highest expression of the NOV10A
gene is detected in TNFalpha+IL-1beta treated small airway
epithelium (CTs=30.4). In addition, significant expression of this
gene is also seen in resting and cytokine treated NCI-H292 cells, a
human airway epithelial cell line that produces mucins and
TNFalpha+IL1beta treated bronchial epithelium. Mucus overproduction
is an important feature of bronchial asthma and chronic obstructive
pulmonary disease samples. Therefore, therapeutics designed with
the protein encoded by the gene may reduce or eliminate symptoms
caused by inflammation in lung epithelia in chronic obstructive
pulmonary disease, asthma, allergy, and emphysema. Please see
AI_comprehensive panel_v1.0 for further discussion of the potential
utility of this gene.
[0629] Ag4254 Expression of this gene is low/undetectable
(CTs>35) across all of the samples on this panel (data not
shown).
[0630] General oncology screening panel_v.sub.--2.4 Summary: Ag4254
Expression of the NOV10A gene is low/undetectable (CTs>35)
across all of the samples on this panel (data not shown).
[0631] I. NOV11A: DENN Domain Containing Protein
[0632] Expression of gene NOV11A was assessed using the
primer-probe set Ag4266, described in Table IA. Results of the
RTQ-PCR runs are shown in Table IB. TABLE-US-00146 TABLE IA Probe
Name Ag4266 Start SEQ ID Primers Sequences Length Position No
Forward 5'-cctttgacgttgaaaggtacag-3' 22 167 157 Probe
TET-5'-tcaagttggacagcactttacctttg-3'- 26 195 158 TAMRA Reverse
5'-tctgcagaatccaaatctctgt-3' 22 243 159
[0633] TABLE-US-00147 TABLE IB CNS_neurodegeneration_v1.0 Rel.
Exp.(%) Rel. Exp.(%) Ag4266, Run Ag4266, Run Tissue Name 224076199
Tissue Name 224076199 AD 1 Hippo 0.0 Control (Path) 3 13.6 Temporal
Ctx AD 2 Hippo 17.2 Control (Path) 4 25.7 Temporal Ctx AD 3 Hippo
7.8 AD 1 Occipital 9.5 Ctx AD 4 Hippo 5.8 AD 2 Occipital 0.0 Ctx
(Missing) AD 5 hippo 23.2 AD 3 Occipital 12.6 Ctx AD 6 Hippo 100.0
AD 4 Occipital 13.0 Ctx Control 2 Hippo 2.3 AD 5 Occipital 33.2 Ctx
Control 4 Hippo 12.2 AD 6 Occipital 6.3 Ctx Control (Path) 3 4.0
Control 1 0.0 Hippo Occipital Ctx AD 1 Temporal Ctx 10.3 Control 2
19.2 Occipital Ctx AD 2 Temporal Ctx 8.7 Control 3 7.9 Occipital
Ctx AD 3 Temporal Ctx 3.9 Control 4 3.9 Occipital Ctx AD 4 Temporal
Ctx 12.0 Control (Path) 1 9.2 Occipital Ctx AD 5 Inf Temporal 47.6
Control (Path) 2 5.8 Ctx Occipital Ctx AD 5 SupTemporal 21.9
Control (Path) 3 0.0 Ctx Occipital Ctx AD 6 Inf Temporal 60.7
Control (Path) 4 2.6 Ctx Occipital Ctx AD 6 Sup Temporal 60.7
Control 1 Parietal 13.1 Ctx Ctx Control 1 Temporal 0.0 Control 2
Parietal 24.3 Ctx Ctx Control 2 Temporal 2.6 Control 3 Parietal
11.0 Ctx Ctx Control 3 Temporal 15.8 Control (Path) 1 7.7 Ctx
Parietal Ctx Control 4 Temporal 0.0 Control (Path) 2 18.7 Ctx
Parietal Ctx Control (Path) 1 13.8 Control (Path) 3 5.0 Temporal
Ctx Parietal Ctx Control (Path) 2 18.7 Control (Path) 4 23.0
Temporal Ctx Parietal Ctx
[0634] CNS_neurodegeneration_v1.0 Summary: Ag4266 This panel
confirms the expression of the NOV11A gene at low levels in the
brains of an independent group of individuals. However, no
differential expression of this gene was detected between
Atzheimer's diseased postmortem brains and those of non-demented
controls in this experiment. Low expression of this gene in the
brain suggests that this gene may play a role in central nervous
system and therapeutic modulation of this gene product may be
useful in the treatment of CNS disorders such as Alzheimer's
disease, Parkinson's disease, epilepsy, multiple sclerosis,
schizophrenia and depression.
[0635] General_screening_panel_v1.4 Summary: Ag4266 Expression of
the NOV11A gene is low/undetectable (CTs>35) across all of the
samples on this panel (data not shown).
[0636] Panel 4.1D Summary: Ag4266 Expression of the NOV11A gene is
low/undetectable (CTs>35) across all of the samples on this
panel (data not shown).
[0637] J. NOV12A and NOV12F: Kininogen Precursor
[0638] Expression of gene NOV12A and variant NOV12F was assessed
using the primer-probe sets Ag3374, Ag4279 and Ag5114, described in
Tables JA, JB and JC. The NOV12A gene is recognized by primer-probe
sets Ag3374 and Ag4279, whereas variant NOV12F is recognized by
primer-probe sets Ag3374 and Ag5114. Results of the RTQ-PCR runs
are shown in Tables JD, JE, JF, and JG. TABLE-US-00148 TABLE JA
Probe Name Ag3374 Start SEQ ID Primers Sequences Length Position No
Forward 5'gattgcaacgctgaagtttatg-3' 22 961 160 Probe
TET-5'-ctgtcaactgtcaaccactgggaatg-3'- 26 1013 161 TAMRA Reverse
5'-gaggccttttcatcagtgagat-3' 22 1039 162
[0639] TABLE-US-00149 TABLE JB Probe Name Ag4279 Start SEQ ID
Primers Sequences Length Position No Forward
5'-aatcttcactccaggcacatag-3' 22 1209 163 Probe
TET-5'-acctctgccagcaaccttgagagg-3'- 24 1239 164 Probe TAMRA Reverse
5'-tcccatctttcttcttgtcctt-3' 22 1263 165
[0640] TABLE-US-00150 TABLE JC Probe Name Ag5114 Start SEQ ID
Primers Sequences Length Position No Forward
5'-acgcagagcccaggtttt-3' 18 364 166 Probe
TET-5'-tcacctttccgatcatcacgaataggg-3'- 27 382 167 TAMRA Reverse
5'-cgcaggaccttaggtgactagt-3' 22 427 168
[0641] TABLE-US-00151 TABLE JD Panel 1.3D Rel. Exp.(%) Ag3374, Run
Rel. Exp.(%) Ag3374, Run Tissue Name 165678152 Tissue Name
165678152 Liver adenocarcinoma 0.0 Kidney (fetal) 6.0 Pancreas 0.0
Renal ca. 786-0 0.0 Pancreatic ca. CAPAN 2 0.0 Renal ca. A498 0.0
Adrenal gland 0.0 Renal ca. RXF 393 0.0 Thyroid 0.0 Renal ca. ACHN
0.0 Salivary gland 0.0 Renal ca. UO-31 0.0 Pituitary gland 0.0
Renal ca. TK-10 0.0 Brain (fetal) 0.0 Liver 100.0 Brain (whole) 0.1
Liver (fetal) 32.1 Brain (amygdala) 0.0 Liver ca. 0.0 (hepatoblast)
HepG2 Brain (cerebellum) 0.0 Lung 0.0 Brain (hippocampus) 0.0 Lung
(fetal) 0.0 Brain (substantia nigra) 0.0 Lung ca. (small cell) 0.0
LX-1 Brain (thalamus) 0.0 Lung ca. (small cell) 0.0 NCI-H69
Cerebral Cortex 0.0 Lung ca. (s. cell var.) 0.0 SHP-77 Spinal cord
0.0 Lung ca. (large 0.0 cell)NCI-H460 glio/astro U87-MG 0.0 Lung
ca. (non-sm. 0.0 cell) A549 glio/astro U-118-MG 0.0 Lung ca.
(non-s. cell) 0.0 NCI-H23 astrocytoma SW1783 0.0 Lung ca. (non-s.
cell) 0.0 HOP-62 neuro*; met SK-N-AS 0.0 Lung ca. (non-s. cl) 0.0
NCI-H522 astrocytoma SF-539 0.0 Lung ca. (squam.) 0.0 SW 900
astrocytoma SNB-75 0.0 Lung ca. (squam.) 0.0 NCI-H596 glioma SNB-19
0.0 Mammary gland 0.0 glioma U251 0.0 Breast ca.* (pl.ef) 0.0 MCF-7
glioma SF-295 0.0 Breast ca.* (pl.ef) 0.0 MDA-MB-231 Heart (fetal)
0.0 Breast ca.* (pl.ef) 0.0 T47D Heart 0.0 Breast ca. BT-549 0.0
Skeletal muscle (fetal) 0.0 Breast ca. MDA-N 0.0 Skeletal muscle
0.0 Ovary 0.0 Bone marrow 0.0 Ovarian ca. 0.0 OVCAR-3 Thymus 0.0
Ovarian ca. 0.0 OVCAR-4 Spleen 0.0 Ovarian ca. 0.0 OVCAR-5 Lymph
node 0.0 Ovarian ca. 0.0 OVCAR-8 Colorectal 0.0 Ovarian ca. IGROV-1
0.0 Stomach 0.0 Ovarian ca.* 0.0 (ascites) SK-OV-3 Small intestine
0.0 Uterus 0.0 Colon ca. SW480 0.0 Placenta 0.0 Colon ca.* 0.0
Prostate 0.0 SW620(SW480 met) Colon ca. HT29 0.0 Prostate ca.*
(bone 0.0 met)PC-3 Colon ca. HCT-116 0.0 Testis 0.0 Colon ca.
CaCo-2 1.4 Melanoma 0.0 Hs688(A).T Colon ca. 0.0 Melanoma* (met)
0.0 tissue(ODO3866) Hs688(B).T Colon ca. HCC-2998 0.0 Melanoma
UACC- 0.0 62 Gastric ca.* (liver met) 0.0 Melanoma M14 0.0 NCI-N87
Bladder 0.0 Melanoma LOX 0.0 IMVI Trachea 0.0 Melanoma* (met) 0.0
SK-MEL-5 Kidney 32.3 Adipose 0.0
[0642] TABLE-US-00152 TABLE JE Panel 2D Rel. Exp.(%) Rel. Exp.(%)
Ag3374, Run Ag3374, Run Tissue Name 170858346 Tissue Name 170858346
Normal Colon 0.7 Kidney Margin 4.2 8120608 CC Well to Mod Diff 0.0
Kidney Cancer 0.1 (ODO3866) 8120613 CC Margin (ODO3866) 0.0 Kidney
Margin 3.1 8120614 CC Gr.2 rectosigmoid 0.0 Kidney Cancer 0.0
(ODO3868) 9010320 CC Margin (ODO3868) 0.0 Kidney Margin 4.4 9010321
CC Mod Diff 0.0 Normal Uterus 0.0 (ODO3920) CC Margin (ODO3920) 0.0
Uterus Cancer 0.1 064011 CC Gr.2 ascend colon 0.0 Normal Thyroid
0.0 (ODO3921) CC Margin (ODO3921) 0.0 Thyroid Cancer 0.0 064010 CC
from Partial 6.8 Thyroid Cancer 0.0 Hepatectomy (ODO4309) Mets
A302152 Liver Margin 100.0 Thyroid Margin 0.0 (ODO4309) A302153
Colon mets to lung 0.0 Normal Breast 0.0 (OD04451-01) Lung Margin
0.0 Breast Cancer 0.0 (OD04451-02) (OD04566) Normal Prostate 6546-1
0.0 Breast Cancer 0.0 (OD04590-01) Prostate Cancer 0.0 Breast
Cancer Mets 0.0 (OD04410) (OD04590-03) Prostate Margin 0.0 Breast
Cancer 0.0 (OD04410) Metastasis (OD04655-05) Prostate Cancer 0.0
Breast Cancer 0.3 (OD04720-01) 064006 Prostate Margin (OD04720-02)
0.0 Breast Cancer 1024 0.0 Normal Lung 061010 0.1 Breast Cancer 0.0
9100266 Lung Met to Muscle 0.0 Breast Margin 0.0 (ODO4286) 9100265
Muscle Margin 0.0 Breast Cancer 0.0 (ODO4286) A209073 Lung
Malignant Cancer 0.0 Breast Margin 0.0 (OD03126) A209073 Lung
Margin 0.0 Normal Liver 60.7 (OD03126) Lung Cancer (OD04404) 0.0
Liver Cancer 064003 78.5 Lung Margin 0.0 Liver Cancer 1025 42.6
(OD04404) Lung Cancer (OD04565) 0.0 Liver Cancer 1026 19.2 Lung
Margin 0.0 Liver Cancer 6004-T 36.9 (OD04565) Lung Cancer
(OD04237-01) 0.0 Liver Tissue 6004-N 3.6 Lung Margin 0.0 Liver
Cancer 6005-T 17.1 (OD04237-02) Ocular Mel Met to Liver 0.0 Liver
Tissue 6005-N 8.6 (ODO4310) Liver Margin 76.3 Normal Bladder 0.0
(ODO4310) Melanoma Mets to Lung 0.0 Bladder Cancer 1023 0.0
(OD04321) Lung Margin 0.0 Bladder Cancer 0.0 (OD04321) A302173
Normal Kidney 48.6 Bladder Cancer 0.0 (OD04718-01) Kidney Ca,
Nuclear 1.6 Bladder Normal 0.0 grade 2 (OD04338) Adjacent (OD04718-
03) Kidney Margin 24.3 Normal Ovary 0.0 (OD04338) Kidney Ca Nuclear
0.0 Ovarian Cancer 0.0 grade 1/2 (OD04339) 064008 Kidney Margin
28.3 Ovarian Cancer 0.0 (OD04339) (OD04768-07) Kidney Ca, Clear
cell 0.0 Ovary Margin 0.0 type (OD04340) (OD04768-08) Kidney Margin
(OD04340) 26.8 Normal Stomach 0.0 Kidney Ca, Nuclear 0.0 Gastric
Cancer 0.0 grade 3 (OD04348) 9060358 Kidney Margin 17.2 Stomach
Margin 0.0 (OD04348) 9060359 Kidney Cancer 0.0 Gastric Cancer 0.0
(OD04622-01) 9060395 Kidney Margin 2.6 Stomach Margin 0.0
(OD04622-03) 9060394 Kidney Cancer 0.0 Gastric Cancer 0.0
(OD04450-01) 9060397 Kidney Margin 32.1 Stomach Margin 0.0
(OD04450-03) 9060396 Kidney Cancer 8120607 0.0 Gastric Cancer 0.0
064005
[0643] TABLE-US-00153 TABLE JF Panel 3D Rel. Exp.(%) Rel. Exp.(%)
Ag3374, Run Ag3374, Run Tissue Name 165039071 Tissue Name 165039071
Daoy-Medulloblastoma 0.0 Ca Ski-Cervical epidermoid 0.0 carcinoma
(metastasis) TE671- 0.0 ES-2-Ovarian clear cell 0.0 Medulloblastoma
carcinoma D283 Med- 0.0 Ramos-Stimulated with 2.3 Medulloblastoma
PMA/ionomycin 6 h PFSK-1-Primitive 0.0 Ramos-Stimulated with 0.0
Neuroectodermal PMA/ionomycin 14 h XF-498-CNS 0.0 MEG-01-Chronic
0.0 myelogenous leukemia (megokaryoblast) SNB-78-Glioma 0.0
Raji-Burkitt's lymphoma 0.0 SF-268-Glioblastoma 0.0 Daudi-Burkitt's
lymphoma 0.0 T98G-Glioblastoma 0.0 U266-B-cell plasmacytoma 0.0
SK-N-SH- 0.0 CA46-Burkitt's lymphoma 0.0 Neuroblastoma (metastasis)
SF-295-Glioblastoma 0.0 RL-non-Hodgkin's B-cell 0.0 lymphoma
Cerebellum 0.0 JM1-pre-B-cell lymphoma 0.0 Cerebellum 0.0 Jurkat-T
cell leukemia 0.0 NCI-H292- 0.0 TF-1-Erythroleukemia 0.0
Mucoepidermoid lung carcinoma DMS-114-Small cell 0.0 HUT 78-T-cell
lymphoma 0.0 lung cancer DMS-79-Small cell 0.0 U937-Histiocytic 0.0
lung cancer lymphoma NCI-H146-Small cell 0.0 KU-812-Myelogenous 0.0
lung cancer leukemia NCI-H526-Small cell 0.0 769-P-Clear cell renal
0.0 lung cancer carcinoma NCI-N417-Small cell 0.0 Caki-2-Clear cell
renal 0.0 lung cancer carcinoma NCI-H82-Small cell 0.0 SW 839-Clear
cell renal 0.0 lung cancer carcinoma NCI-H157-Squamous 0.0
G401-Wilms' tumor 0.0 cell lung cancer (metastasis) NCI-H1155-Large
cell 0.0 Hs766T-Pancreatic 0.0 lung cancer carcinoma (LN
metastasis) NCI-H1299-Large cell 0.0 CAPAN-1-Pancreatic 0.0 lung
cancer adenocarcinoma (liver metastasis) NCI-H727-Lung 0.0
SU86.86-Pancreatic 0.0 carcinoid carcinoma (liver metastasis)
NCI-UMC-11-Lung 0.0 BxPC-3-Pancreatic 0.0 carcinoid adenocarcinoma
LX-1-Small cell lung 0.0 HPAC-Pancreatic 0.0 cancer adenocarcinoma
Colo-205-Colon cancer 0.0 MIA PaCa-2-Pancreatic 0.0 carcinoma
KM12-Colon cancer 0.0 CFPAC-1-Pancreatic ductal 0.0 adenocarcinoma
KM20L2-Colon cancer 0.0 PANC-1-Pancreatic 0.0 epithelioid ductal
carcinoma NCI-H716-Colon 0.0 T24-Bladder carcinma 0.0 cancer
(transitional cell) SW-48-Colon 100.0 5637-Bladder carcinoma 0.0
adenocarcinoma SW1116-Colon 0.0 HT-1197-Bladder 0.0 adenocarcinoma
carcinoma LS 174T-Colon 79.6 UM-UC-3-Bladder 0.0 adenocarcinoma
carcinma (transitional cell) SW-948-Colon 0.0 A204-Rhabdomyosarcoma
0.0 adenocarcinoma SW-480-Colon 0.0 HT-1080-Fibrosarcoma 0.0
adenocarcinoma NCI-SNU-5-Gastric 0.0 MG-63-Osteosarcoma 0.0
carcinoma KATO III-Gastric 4.2 SK-LMS-1- 0.0 carcinoma
Leiomyosarcoma (vulva) NCI-SNU-16-Gastric 0.0 SJRH30- 0.0 carcinoma
Rhabdomyosarcoma (met to bone marrow) NCI-SNU-1-Gastric 0.0
A431-Epidermoid 0.0 carcinoma carcinoma RF-1-Gastric 0.0
WM266-4-Melanoma 0.0 adenocarcinoma RF-48-Gastric 0.0 DU
145-Prostate carcinoma 0.0 adenocarcinoma (brain metastasis)
MKN-45-Gastric 0.0 MDA-MB-468-Breast 0.0 carcinoma adenocarcinoma
NCI-N87-Gastric 0.0 SCC-4-Squamous cell 0.0 carcinoma carcinoma of
tongue OVCAR-5-Ovarian 0.0 SCC-9-Squamous cell 0.0 carcinoma
carcinoma of tongue RL95-2-Uterine 0.0 SCC-15-Squamous cell 0.0
carcinoma carcinoma of tongue HelaS3-Cervical 0.0 CAL 27-Squamous
cell 0.0 adenocarcinoma carcinoma of tongue
[0644] TABLE-US-00154 TABLE JG Panel 4D Rel. Exp.(%) Rel. Exp.(%)
Ag3374, Run Ag3374, Run Tissue Name 165296618 Tissue Name 165296618
Secondary Th1 act 0.0 HUVEC IL-1beta 0.0 Secondary Th2 act 0.0
HUVEC IFN gamma 0.0 Secondary Tr1 act 0.0 HUVEC TNF alpha + IFN 0.0
gamma Secondary Th1 rest 0.0 HUVEC TNF alpha + IL4 0.0 Secondary
Th2 rest 0.0 HUVEC IL-11 0.0 Secondary Tr1 rest 0.0 Lung
Microvascular EC 0.0 none Primary Th1 act 0.0 Lung Microvascular EC
0.0 TNF alpha + IL-1beta Primary Th2 act 0.0 Microvascular Dermal
0.0 EC none Primary Tr1 act 0.0 Microvasular Dermal 0.0 EC TNF
alpha + IL-1beta Primary Th1 rest 0.0 Bronchial epithelium 0.0 TNF
alpha + IL1beta Primary Th2 rest 0.0 Small airway epithelium 0.0
none Primary Tr1 rest 0.0 Small airway epithelium 0.0 TNF alpha +
IL-1beta CD45RA CD4 0.0 Coronery artery SMC 0.0 lymphocyte act rest
CD45RO CD4 0.0 Coronery artery SMC 0.0 lymphocyte act TNF alpha +
IL-1beta CD8 lymphocyte act 0.0 Astrocytes rest 0.0 Secondary CD8
0.0 Astrocytes TNF alpha + IL- 0.0 lymphocyte rest 1beta Secondary
CD8 0.0 KU-812 (Basophil) rest 0.0 lymphocyte act CD4 lymphocyte
none 0.0 KU-812 (Basophil) 0.0 PMA/ionomycin 2ry Th1/Th2/Tr1_anti-
0.0 CCD1106 0.0 CD95 CH11 (Keratinocytes) none LAK cells rest 0.0
CCD1106 0.0 (Keratinocytes) TNF alpha + IL-1beta LAK cells IL-2 0.0
Liver cirrhosis 11.6 LAK cells IL-2 + IL-12 0.0 Lupus kidney 0.7
LAK cells IL-2 + IFN 0.0 NCI-H292 none 0.0 gamma LAK cells IL-2 +
IL-18 0.0 NCI-H292 IL-4 0.0 LAK cells 0.0 NCI-H292 IL-9 0.0
PMA/ionomycin NK Cells IL-2 rest 0.0 NCI-H292 IL-13 0.0 Two Way MLR
3 day 0.0 NCI-H292 IFN gamma 0.0 Two Way MLR 5 day 0.0 HPAEC none
0.0 Two Way MLR 7 day 0.0 HPAEC TNF alpha + IL- 0.0 1beta PBMC rest
0.0 Lung fibroblast none 0.0 PBMC PWM 0.0 Lung fibroblast TNF 0.0
alpha + IL-1beta PBMC PHA-L 0.0 Lung fibroblast IL-4 0.0 Ramos (B
cell) none 0.0 Lung fibroblast IL-9 0.0 Ramos (B cell) 0.0 Lung
fibroblast IL-13 0.0 ionomycin B lymphocytes PWM 0.0 Lung
fibroblast IFN 0.0 gamma B lymphocytes CD40L 0.0 Dermal fibroblast
0.0 and IL-4 CCD1070 rest EOL-1 dbcAMP 0.0 Dermal fibroblast 0.0
CCD1070 TNF alpha EOL-1 dbcAMP 0.0 Dermal fibroblast 0.0
PMA/ionomycin CCD1070 IL-1beta Dendritic cells none 0.0 Dermal
fibroblast IFN 0.0 gamma Dendritic cells LPS 0.0 Dermal fibroblast
IL-4 0.0 Dendritic cells anti- 0.0 IBD Colitis 2 0.0 CD40 Monocytes
rest 0.0 IBD Crohn's 0.0 Monocytes LPS 0.0 Colon 0.0 Macrophages
rest 0.0 Lung 0.0 Macrophages LPS 0.0 Thymus 100.0 HUVEC none 0.0
Kidney 0.0 HUVEC starved 0.0
[0645] CNS_neurodegeneration_v1.0 Summary: Ag5114 Expression of the
NOV12F gene is low/undetectable (CTs>35) in all samples on this
panel (data not shown).
[0646] General_screening_panel_v1.5 Summary: Ag5114 Expression of
the NOV12F gene is low/undetectable (CTs>35) in all samples on
this panel (data not shown).
[0647] Panel 1.3D Summary: Ag3374 Expression of this gene is
restricted to a few samples, with highest expression in liver
(CT=24.1), fetal liver, and kidney. Moderate expression is seen in
fetal kidney and low levels of expression are seen in a colon
cancer cell line. This expression profile suggests that this gene
could be used to differentiate between liver and other samples on
this panel and as a marker of liver and kidney tissue.
[0648] Panel 2D Summary: Ag3374 Highest expression of this gene is
seen in liver derived tissue (CT=23.9), with expression in this
panel restricted to liver and kidney derived tissue. This
expression is in agreement with expression seen in Panel 1.3D. In
addition, this gene is more highly expressed in kidney tissue when
compared to normal adjacent tissue. This gene encodes a putative
kininogen, which has been shown to inhibit angiogenesis (Colman R.
Blood. 95:543; Guo Y. Arterioscler Thromb Vasc Biol. September
2001, pg. 1427). The expressed protein can also be used in the
treatment of kidney cancers as it is not expressed in kidney
cancers compared to the adjacent normal tissues and inhibition of
its activity using antibodies or small molecule drugs may be useful
in treating liver cancer. Thus, therapeutic modulation of the
expression or function of this gene could be effective in the
treatment of liver and kidney cancers.
[0649] Panel 3D Summary: Ag3374 Expression in this panel is
restricted to samples derived from colon cancer cell lines
(CTs=34-35). Thus, expression of this gene could be used to
differentiate between this sample and other samples on this panel
and as a marker to detect the presence of colon cancer.
Furthermore, therapeutic modulation of the expression or function
of this gene may be effective in the treatment of colon cancer. A
second experiment with probe and primer set Ag4269 shows
low/undetectable levels of expression (CTs>35). (Data not
shown.)
[0650] Panel 4D Summary: Ag3374 This transcript is most highly
expressed in the thymus (CT=24.3). The protien encoded by this gene
could therefore play an important role in T cell development. Thus,
therapeutic modulation of the expression or function of this gene
may modulate immune function (T cell development) and be important
for organ transplant, AIDS treatment or post chemotherapy immune
reconstitution.
[0651] In addition, moderate levels of expression are seen in liver
cirrhosis and lupus kidney, in agreement with previous panels that
showed expression in liver and kidney derived tissues.
[0652] Panel 4.1D Summary: Ag5114 Expression of the NOV12F gene is
low/undetectable (CTs>35) in all samples on this panel (data not
shown).
[0653] General oncology screening panel_v.sub.--2.4 Summary: Ag5114
Expression of the NOV12F gene is low/undetectable (CTs>35) in
all samples on this panel (data not shown).
[0654] K. NOV12B, NOV12C, NOV12D, NOV12E, NOV12G and CG104903-09:
Kininogen Precursor
[0655] Expression of gene NOV12B and variants NOV12C, NOV12D,
NOV12E, NOV12G and NOV12H was assessed using the primer-probe sets
Ag3374, Ag4269, Ag5115 and Ag5116, described in Tables KA, KB, KC
and KD. The correspondence of primer-probe sets to the various
variants is described in Table KE. These sequences are variants of
NOV12A described in the previous section (section J). Results of
the RTQ-PCR runs are shown in Tables KE, KF, KG, KH, KI, KJ, KK,
KL, KM, KN and KO. Please note that NOV12G represents a full-length
physical clone. In addition, NOV12H represents a full-length
physical clone that validates the prediction of the NOV12C
sequence. TABLE-US-00155 TABLE KA Probe Name Ag3374 Start SEQ ID
Primers Sequences Length Position No Forward
5'-gattgcaacgctgaagtttatg-3' 22 1005 169 Probe
TET-5'-ctgtcaactgtcaaccactgggaatg-3'- 26 1057 170 TAMRA Reverse
5'-gaggccttttcatcagtgagat-3' 22 1083 171
[0656] TABLE-US-00156 TABLE KB Probe Name Ag4269 Start SEQ ID
Primers Sequences Length Position No Forward
5'-acagagcatttggcaagct-3' 19 1518 172 Probe TET-5'-
cagtactacaccttctgcacagacaca-3'- 27 1547 173 TAMRA Reverse
5'-gttggcccttctgtcttctc-3' 20 1575 174
[0657] TABLE-US-00157 TABLE KC Probe Name Ag5115 Start SEQ ID
Primers Sequences Length Position No Forward
5'-cagccactggagaatgca-3' 18 354 175 Probe
TET-5'-agcagtacgaaattctccgtggctacc-3'- 27 391 176 TAMRA Reverse
5'-gaatgggctccaggtctg-3' 18 418 177
[0658] TABLE-US-00158 TABLE KD Probe Name Ag5116 Start SEQ ID
Primers Sequences Length Position No Forward
5'-acgcagagcccaggtttt-3' 18 500 178 Probe
TET-5'-cacctttccgatcatcacgaatagggg-3'- 27 519 179 TAMRA Reverse
5'-gggtggacttacagttgtttcttct-3' 25 553 180
[0659] TABLE-US-00159 TABLE KE Probe Name Ag3374 NOV12B NOV12C
NOV12D NOV12E NOV12G NOV12H Ag3374 X X X X X Ag4269 X X X X Ag5115
X Ag5116 X
[0660] TABLE-US-00160 TABLE KF CNS_neurodegeneration_v1.0 Rel.
Exp.(%) Rel. Exp.(%) Rel. Exp.(%) Rel. Exp.(%) Tissue Ag4269, Run
Ag5115, Run Tissue Ag4269, Run Ag5115, Run Name 217215423 226443863
Name 217215423 226443863 AD 1 Hippo 0.0 0.0 Control 0.0 0.0 (Path)
3 Temporal Ctx AD 2 Hippo 0.0 3.1 Control 13.9 11.5 (Path) 4
Temporal Ctx AD 3 Hippo 0.0 0.0 AD 1 26.8 4.9 Occipital Ctx AD 4
Hippo 39.5 0.0 AD 2 0.0 0.0 Occipital Ctx (Missing) AD 5 Hippo
100.0 100.0 AD 3 0.0 0.0 Occipital Ctx AD 6 Hippo 0.0 0.0 AD 4 8.1
9.2 Occipital Ctx Control 2 0.0 0.0 AD 5 24.8 3.6 Hippo Occipital
Ctx Control 4 0.0 0.0 AD 6 0.0 98.6 Hippo Occipital Ctx Control 0.0
0.0 Control 1 0.0 0.0 (Path) 3 Occipital Hippo Ctx AD 1 0.0 0.0
Control 2 57.8 85.9 Temporal Occipital Ctx Ctx AD 2 12.9 7.9
Control 3 24.0 4.0 Temporal Occipital Ctx Ctx AD 3 0.0 0.0 Control
4 0.0 0.0 Temporal Occipital Ctx Ctx AD 4 30.4 2.9 Control 79.0
54.0 Temporal (Path) 1 Ctx Occipital Ctx AD 5 Inf 28.9 12.8 Control
42.0 5.3 Temporal (Path) 2 Ctx Occipital Ctx AD 5 Sup 0.0 0.0
Control 0.0 0.0 Temporal (Path) 3 Ctx Occipital Ctx AD 6 Inf 0.0
2.3 Control 34.6 12.4 Temporal (Path) 4 Ctx Occipital Ctx AD 6 Sup
35.1 3.8 Control 1 0.0 0.0 Temporal Parietal Ctx Ctx Control 1 0.0
0.0 Control 2 0.0 6.7 Temporal Parietal Ctx Ctx Control 2 17.6 4.0
Control 3 7.2 6.4 Temporal Parietal Ctx Ctx Control 3 14.2 0.0
Control 16.4 63.3 Temporal (Path) 1 Ctx Parietal Ctx Control 3 0.0
0.0 Control 32.8 20.0 Temporal (Path) 2 Ctx Parietal Ctx Control
27.2 13.1 Control 1.1 0.0 (Path) 1 (Path) 3 Temporal Parietal Ctx
Ctx Control 26.4 12.9 Control 86.5 35.4 (Path) 2 (Path) 4 Temporal
Parietal Ctx Ctx
[0661] TABLE-US-00161 TABLE KG General_screening_panel_v1.4 Rel.
Exp.(%) Rel. Exp.(%) Ag4269, Run Ag4269, Run Tissue Name 217044119
Tissue Name 217044119 Adipose 0.0 Renal ca. TK-10 0.0 Melanoma*
Hs688(A).T 0.0 Bladder 0.1 Melanoma* Hs688(B).T 0.0 Gastric ca.
(liver met.) 0.0 NCI-N87 Melanoma* M14 0.0 Gastric ca. KATO III 0.0
Melanoma* LOXIMVI 0.0 Colon ca. SW-948 0.0 Melanoma* SK-MEL-5 0.1
Colon ca. SW480 0.0 Squamous cell 0.0 Colon ca.* (SW480 0.0
carcinoma SCC-4 met) SW620 Testis Pool 0.0 Colon ca. HT29 0.0
Prostate ca.* (bone 0.0 Colon ca. HCT-116 0.0 met) PC-3 Prostate
Pool 0.0 Colon ca. CaCo-2 5.8 Placenta 0.0 Colon cancer tissue 0.2
Uterus Pool 0.0 Colon ca. SW1116 0.0 Ovarian ca. 0.0 Colon ca.
Colo-205 0.0 OVCAR-3 Ovarian ca. SK-OV-3 0.0 Colon ca. SW-48 0.0
Ovarian ca. 0.0 Colon Pool 0.1 OVCAR-4 Ovarian ca. 0.1 Small
Intestine Pool 0.0 OVCAR-5 Ovarian ca. 0.0 Stomach Pool 0.1 IGROV-1
Ovarian ca. 0.0 Bone Marrow Pool 0.0 OVCAR-8 Ovary 0.0 Fetal Heart
0.0 Breast ca. MCF-7 0.0 Heart Pool 0.0 Breast ca. MDA- 0.0 Lymph
Node Pool 0.0 MB-231 Breast ca. BT 549 0.0 Fetal Skeletal Muscle
0.0 Breast ca. T47D 0.0 Skeletal Muscle Pool 0.0 Breast ca. MDA-N
0.0 Spleen Pool 0.0 Breast Pool 0.1 Thymus Pool 0.0 Trachea 0.0 CNS
cancer 0.0 (glio/astro) U87-MG Lung 0.0 CNS cancer 0.0 (glio/astro)
U-118-MG Fetal Lung 0.8 CNS cancer 0.0 (neuro; met) SK-N-AS Lung
ca. NCI-N417 0.0 CNS cancer (astro) SF-539 0.0 Lung ca. LX-1 0.1
CNS cancer (astro) SNB-75 0.0 Lung ca. NCI-H146 0.0 CNS cancer
(glio) SNB-19 0.0 Lung ca. SHP-77 0.0 CNS cancer (glio) SF-295 0.0
Lung ca. A549 0.1 Brain (Amygdala) Pool 0.0 Lung ca. NCI-H526 0.0
Brain (cerebellum) 0.0 Lung ca. NCI-H23 0.0 Brain (fetal) 0.0 Lung
ca. NCI-H460 0.0 Brain (Hippocampus) Pool 0.0 Lung ca. HOP-62 0.0
Cerebral Cortex Pool 0.1 Lung ca. NCI-H522 0.0 Brain (Substantia
0.0 nigra) Pool Liver 20.0 Brain (Thalamus) Pool 0.0 Fetal Liver
100.0 Brain (whole) 1.3 Liver ca. HepG2 0.2 Spinal Cord Pool 0.0
Kidney Pool 0.0 Adrenal Gland 0.1 Fetal Kidney 12.0 Pituitary gland
Pool 0.0 Renal ca. 786-0 0.0 Salivary Gland 0.0 Renal ca. A498 0.0
Thyroid (female) 0.0 Renal ca. ACHN 0.0 Pancreatic ca. 0.0 CAPAN2
Renal ca. UO-31 0.0 Pancreas Pool 0.1
[0662] TABLE-US-00162 TABLE KH General_screening_panel_v1.5 Rel.
Exp.(%) Rel. Exp.(%) Ag5115, Run Ag5115, Run Tissue Name 228738881
Tissue Name 228738881 Adipose 0.0 Renal ca. TK-10 0.0 Melanoma*
Hs688(A).T 0.0 Bladder 0.1 Melanoma* 0.0 Gastric ca. (liver met.)
0.0 Hs688(B).T NCI-N87 Melanoma* M14 0.0 Gastric ca. KATO III 0.0
Melanoma* LOXIMVI 0.0 Colon ca. SW-948 0.0 Melanoma* SK-MEL-5 0.0
colon ca. SW480 0.0 Squamous cell 0.0 Colon ca.* (SW480 0.0
carcinoma SCC-4 0.0 met) SW620 Testis Pool 0.0 Colon ca. HT29 0.0
Prostate ca.* (bone 0.0 Colon ca. HCT-116 0.0 met) PC-3 Prostate
Pool 0.0 Colon ca. CaCo-2 5.4 Placenta 0.0 Colon cancer tissue 0.0
Uterus Pool 0.0 Colon ca. SW1116 0.0 Ovarian ca. 0.0 Colon ca.
Colo-205 0.0 OVCAR-3 Ovarian ca. SK-OV-3 0.0 Colon ca. SW-48 0.0
Ovarian ca. 0.0 Colon Pool 0.0 OVCAR-4 Ovarian ca. 0.0 Small
Intestine Pool 0.0 OVCAR-5 Ovarian ca. 0.0 Stomach Pool 0.0 IGROV-1
Ovarian ca. 0.0 Bone Marrow Pool 0.0 OVCAR-8 Ovary 0.0 Fetal Heart
0.0 Breast ca. MCF-7 0.0 Heart Pool 0.0 Breast ca. MDA- 0.0 Lymph
Node Pool 0.0 MB-231 Breast ca. BT 549 0.0 Fetal Skeletal Muscle
0.0 Breast ca. T47D 0.0 Skeletal Muscle Pool 0.0 Breast ca. MDA-N
0.0 Spleen Pool 0.0 Breast Pool 0.1 Thymus Pool 0.0 Trachea 0.0 CNS
cancer 0.0 (glio/astro) U87-MG Lung 0.0 CNS cancer 0.0 (glio/astro)
U-118-MG Fetal Lung 0.8 CNS cancer 0.0 (neuro; met) SK-N-AS Lung
ca. NCI-N417 0.0 CNS cancer (astro) SF-539 0.0 Lung ca. LX-1 0.0
CNS cancer (astro) 0.0 SNB-75 Lung ca. NCI-H146 0.0 CNS cancer
(glio) 0.0 SNB-19 Lung ca. SHP-77 0.0 CNS cancer (glio) SF-295 0.0
Lung ca. A549 0.0 Brain (Amygdala) Pool 0.0 Lung ca. NCI-H526 0.0
Brain (cerebellum) 0.0 Lung ca. NCI-H23 0.0 Brain (fetal) 0.0 Lung
ca. NCI-H460 0.0 Brain (Hippocampus) Pool 0.2 Lung ca. HOP-62 0.0
Cerebral Cortex Pool 0.1 Lung ca. NCI-H522 0.0 Brain (Substantia
0.0 nigra) Pool Liver 27.7 Brain (Thalamus) Pool 0.1 Fetal Liver
100.0 Brain (whole) 1.3 Liver ca. HepG2 0.0 Spinal Cord Pool 0.0
Kidney Pool 0.0 Adrenal Gland 0.0 Fetal Kidney 13.8 Pituitary gland
Pool 0.0 Renal ca. 786-0 0.0 Salivary Gland 0.0 Renal ca. A498 0.0
Thyroid (female) 0.0 Renal ca. ACHN 0.0 Pancreatic ca. 0.0 CAPAN2
Renal ca. UO-31 0.0 Pancreas Pool 0.0
[0663] TABLE-US-00163 TABLE KI Panel 1.3D Rel. Exp.(%) Rel. Exp.(%)
Ag3374, Run Ag3374, Run Tissue Name 165678152 Tissue Name 165678152
Liver adenocarcinoma 0.0 Kidney (fetal) 6.0 Pancreas 0.0 Renal ca.
786-0 0.0 Pancreatic ca. CAPAN 2 0.0 Renal ca. A498 0.0 Adrenal
gland 0.0 Renal ca. RXF 393 0.0 Thyroid 0.0 Renal ca. ACHN 0.0
Salivary gland 0.0 Renal ca. UO-31 0.0 Pituitary gland 0.0 Renal
ca. TK-10 0.0 Brain (fetal) 0.0 Liver 100.0 Brain (whole) 0.1 Liver
(fetal) 32.1 Brain (amygdala) 0.0 Liver ca. 0.0 (hepatoblast) HepG2
Brain (cerebellum) 0.0 Lung 0.0 Brain (hippocampus) 0.0 Lung
(fetal) 0.0 Brain (substantia nigra) 0.0 Lung ca. (small cell) LX-1
0.0 Brain (thalamus) 0.0 Lung ca. (small cell) NCI-H69 0.0 Cerebral
Cortex 0.0 Lung ca. (s. cell var.) SHP-77 0.0 Spinal cord 0.0 Lung
ca. (large 0.0 cell)NCI-H460 glio/astro U87-MG 0.0 Lung ca.
(non-sm. cell) A549 0.0 glio/astro U-118-MG 0.0 Lung ca. (non-s.
cell) 0.0 NCI-H23 astrocytoma SW1783 0.0 Lung ca. (non-s. cell) 0.0
HOP-62 neuro*; met SK-N-AS 0.0 Lung ca. (non-s. cl) 0.0 NCI-H522
astrocytoma SF-539 0.0 Lung ca. (squam.) 0.0 SW 900 astrocytoma
SNB-75 0.0 Lung ca. (squam.) 0.0 NCI-H596 glioma SNB-19 0.0 Mammary
gland 0.0 glioma U251 0.0 Breast ca.* (pl.ef) 0.0 MCF-7 glioma
SF-295 0.0 Breast ca.* (pl.ef) 0.0 MDA-MB-231 Heart (fetal) 0.0
Breast ca.* (pl.ef) 0.0 T47D Heart 0.0 Breast ca. BT-549 0.0
Skeletal muscle (fetal) 0.0 Breast ca. MDA-N 0.0 Skeletal muscle
0.0 Ovary 0.0 Bone marrow 0.0 Ovarian ca. 0.0 OVCAR-3 Thymus 0.0
Ovarian ca. 0.0 OVCAR-4 Spleen 0.0 Ovarian ca. 0.0 OVCAR-5 Lymph
node 0.0 Ovarian ca. 0.0 OVCAR-8 Colorectal 0.0 Ovarian ca. IGROV-1
0.0 Stomach 0.0 Ovarian ca.* 0.0 (ascites) SK-OV-3 Small intestine
0.0 Uterus 0.0 Colon ca. SW480 0.0 Placenta 0.0 Colon ca.* 0.0
Prostate 0.0 SW620(SW480 met) Colon ca. HT29 0.0 Prostate ca.*
(bone 0.0 met)PC-3 Colon ca. HCT-116 0.0 Testis 0.0 Colon ca.
CaCo-2 1.4 Melanoma 0.0 Hs688(A).T Colon ca. 0.0 Melanoma* (met)
0.0 tissue(ODO3866) Hs688(B).T Colon ca. HCC-2998 0.0 Melanoma
UACC-62 0.0 Gastric ca.* (liver met) 0.0 Melanoma M14 0.0 NCI-N87
Bladder 0.0 Melanoma LOX 0.0 IMVI Trachea 0.0 Malanoma* (met) 0.0
SK-MEL-5 Kidney 32.3 Adipose 0.0
[0664] TABLE-US-00164 TABLE KJ Panel 2.2 Rel. Rel. Rel. Rel.
Exp.(%) Exp.(%) Exp.(%) Exp.(%) Ag3374, Run Ag3374, Run Ag3374, Run
Ag3374, Run Tissue Name 176283594 184372611 Tissue Name 176283594
184372611 Normal Colon 0.2 0.3 Kidney Margin 38.4 14.2 (OD04348)
Colon cancer 0.0 0.0 Kidney 0.0 0.0 (OD06064) malignant cancer
(OD06204B) Colon Margin 0.0 0.0 Kidney normal 4.5 4.7 (OD06064)
adjacent tissue (OD06204E) Colon cancer 0.0 0.0 Kidney Cancer 0.0
0.0 (OD06159) (OD04450-01) Colon Margin 0.0 0.0 Kidney Margin 17.9
41.2 (OD06159) (OD04450-03) Colon cancer 0.0 0.0 Kidney Cancer 0.0
0.0 (OD06297-04) 8120613 Colon Margin 0.1 0.0 Kidney Margin 2.9 1.8
(OD06297-05) 8120614 CC Gr.2 ascend 0.0 0.0 Kidney Cancer 2.4 0.0
colon 9010320 (ODO3921) CC Margin 0.0 0.0 Kidney Margin 1.3 1.8
(ODO3921) 9010321 Colon cancer 0.0 0.0 Kidney Cancer 0.0 0.0
metastasis 8120607 (OD06104) Lung Margin 0.0 0.0 Kidney Margin 2.1
2.6 (OD06104) 8120608 Colon mets to 0.0 0.0 Normal Uterus 0.0 0.0
lung (OD04451-01) Lung Margin 0.1 0.0 Uterine Cancer 0.0 0.0
(OD04451-02) 064011 Normal 0.0 0.0 Normal 0.0 0.0 Prostate Thyroid
Prostate Cancer 0.0 0.0 Thyroid Cancer 0.0 0.0 (OD04410) 064010
Prostate Margin 0.0 0.0 Thyroid Cancer 0.0 0.0 (OD04410) A302152
Normal Ovary 0.0 0.0 Thyroid 0.0 0.0 Margin A302153 Ovarian cancer
0.0 0.0 Normal Breast 0.0 0.0 (OD06283-03) Ovarian Margin 0.0 0.0
Breast Cancer 1.3 0.0 (OD06283-07) (OD04566) Ovarian Cancer 1.5 0.0
Breast Cancer 1.6 0.0 064008 1024 Ovarian cancer 5.8 0.0 Breast
Cancer 0.1 0.0 (OD06145) (OD04590-01) Ovarian Margin 1.4 0.0 Breast
Cancer 0.0 0.0 (OD06145) Mets (OD04590-03) Ovarian cancer 0.2 0.0
Breast Cancer 0.0 0.0 (OD06455-03) Metastasis (OD04655-05) Ovarian
Margin 0.0 0.0 Breast Cancer 0.1 0.3 (OD06455-07) 064006 Normal
Lung 0.0 0.0 Breast Cancer 0.0 0.0 9100266 Invasive poor 0.0 0.0
Breast Margin 0.0 0.0 diff. lung adeno 9100265 (ODO4945-01 Lung
Margin 0.0 0.0 Breast Cancer 0.0 0.0 (ODO4945-03) A209073 Lung
Malignant 0.0 0.0 Breast Margin 0.0 0.0 Cancer A2090734 (OD03126)
Lung Margin 0.0 0.0 Breast cancer 0.0 0.0 (OD03126) (OD06083) Lung
Cancer 0.0 0.0 Breast cancer 0.0 0.0 (OD05014A) node metastasis
(OD06083) Lung Margin 0.1 0.0 Normal Liver 57.8 94.6 (OD05014B)
Lung cancer 0.0 0.0 Liver Cancer 8.1 15.1 (OD06081) 1026 Lung
Margin 0.0 0.0 Liver Cancer 47.0 60.3 (OD06081) 1025 Lung Cancer
0.0 0.0 Liver Cancer 23.3 44.8 (OD04237-01) 6004-T Lung Margin 0.0
0.0 Liver Tissue 1.8 1.1 (OD04237-02) 6004-N Ocular 0.0 0.0 Liver
Cancer 21.8 20.7 Melanoma 6005-T Metastasis Ocular 49.7 100.0 Liver
Tissue 31.6 27.0 Melanoma 6005-N Margin (Liver) Melanoma 0.0 0.0
Liver Cancer 100.0 92.7 Metastasis 064003 Melanoma 0.0 0.0 Normal
0.0 0.0 Margin (Lung) Bladder Normal Kidney 8.8 13.6 Bladder Cancer
0.0 0.0 1023 Kidney Ca, 27.9 26.1 Bladder Cancer 0.0 0.0 Nuclear
grade 2 A302173 (OD04338) Kidney Margin 0.2 1.4 Normal 0.2 0.0
(OD04338) Stomach Kidney Ca 0.4 0.0 Gastric Cancer 0.0 0.0 Nuclear
grade 9060397 1/2 (OD04339) Kidney Margin 12.5 15.1 Stomach 0.0 0.0
(OD04339) Margin 9060396 Kidney Ca, 0.0 0.0 Gastric Cancer 0.0 0.0
Clear cell type 9060395 (OD04340) Kidney Margin 17.8 12.4 Stomach
0.0 0.0 (OD04340) Margin 9060394 Kidney Ca, 0.0 0.0 Gastric Cancer
0.0 0.0 Nuclear grade 3 064005 (OD04348)
[0665] TABLE-US-00165 TABLE KK Panel 2D Rel. Exp.(%) Rel. Exp.(%)
Ag3374, Run Ag3374, Run Tissue Name 170858346 Tissue Name 170858346
Normal Colon 0.7 Kidney Margin 4.2 8120608 CC Well to Mod Diff 0.0
Kidney Cancer 0.1 (ODO3866) 8120613 CC Margin (ODO3866) 0.0 Kidney
Margin 3.1 8120614 CC Gr.2 rectosigmoid 0.0 Kidney Cancer 0.0
(ODO3868) 9010320 CC Margin (ODO3868) 0.0 Kidney Margin 4.4 9010321
CC Mod Diff 0.0 Normal Uterus 0.0 (ODO3920) CC Margin (ODO3920) 0.0
Uterus Cancer 0.1 064011 CC Gr.2 ascend colon 0.0 Normal Thyroid
0.0 (ODO3921) CC Margin (ODO3921) 0.0 Thyroid Cancer 0.0 064010 CC
from Partial 6.8 Thyroid Cancer 0.0 Hepatectomy (ODO4309) Mets
A302152 Liver Margin 100.0 Thyroid Margin 0.0 (ODO4309) A302153
Colon mets to lung 0.0 Normal Breast 0.0 (OD04451-01) Lung Margin
0.0 Breast Cancer 0.0 (OD04451-02) (OD04566) Normal Prostate 6546-1
0.0 Breast Cancer 0.0 (OD04590-01) Prostate Cancer 0.0 Breast
Cancer Mets 0.0 (OD04410) (OD04590-03) Prostate Margin 0.0 Breast
Cancer 0.0 (OD04410) Metastasis (OD04655-05) Prostate Cancer 0.0
Breast Cancer 0.3 (OD04720-01) 064006 Prostate Margin 0.0 Breast
Cancer 1024 0.0 (OD04720-02) Normal Lung 061010 0.1 Breast Cancer
0.0 9100266 Lung Met to Muscle 0.0 Breast Margin 0.0 (ODO4286)
9100265 Muscle Margin 0.0 Breast Cancer 0.0 (ODO4286) A209073 Lung
Malignant Cancer 0.0 Breast Margin 0.0 (OD03126) A209073 Lung
Margin (OD03126) 0.0 Normal Liver 60.7 Lung Cancer (OD04404) 0.0
Liver Cancer 064003 78.5 Lung Margin (OD04404) 0.0 Liver Cancer
1025 42.6 Lung Cancer (OD04565) 0.0 Liver Cancer 1026 19.2 Lung
Margin (OD04565) 0.0 Liver Cancer 6004-T 36.9 Lung Cancer
(OD04237-01) 0.0 Liver Tissue 6004-N 3.6 Lung Margin 0.0 Liver
Cancer 6005-T 17.1 (OD04237-02) Ocular Mel Met to Liver 0.0 Liver
Tissue 6005-N 8.6 (ODO4310) Liver Margin (ODO4310) 76.3 Normal
Bladder 0.0 Melanoma Mets to Lung 0.0 Bladder Cancer 1023 0.0
(OD04321) Lung Margin 0.0 Bladder Cancer 0.0 (OD04321) A302173
Normal Kidney 48.6 Bladder Cancer 0.0 (OD04718-01) Kidney Ca,
Nuclear 1.6 Bladder Normal 0.0 grade 2(OD04338) Adjacent
(OD04718-03) 0.0 Kidney Margin (OD04338) 24.3 Normal Ovary 0.0
Kidney Ca Nuclear 0.0 Ovarian Cancer 0.0 grade 1/2 (OD04339)
(OD04768-07) Kidney Margin 28.3 Ovarian Cancer 0.0 (OD04339)
(OD04768-07) Kidney Ca, Clear cell 0.0 Ovary Margin 0.0 type
(OD04340) (OD04768-08) Kidney Margin (OD04340) 26.8 Normal Stomach
0.0 Kidney Ca, Nuclear 0.0 Gastric Cancer 0.0 grade 3 (OD04348)
9060358 Kidney Margin 17.2 Stomach Margin 0.0 (OD04348) 9060359
Kidney Cancer 0.0 Gastric Cancer 0.0 (OD04622-01) 9060395 Kidney
Margin 2.6 Stomach Margin 0.0 (OD04622-03) 9060394 Kidney Cancer
0.0 Gastric Cancer 0.0 (OD04450-01) 9060397 Kidney Margin 32.1
Stomach Margin 0.0 (OD04450-03) 9060396 Kidney Cancer 8120607 0.0
Gastric Cancer 0.0 064005
[0666] TABLE-US-00166 TABLE KL Panel 3D Rel. Exp.(%) Rel. Exp.(%)
Ag3374, Run Ag3374, Run Tissue Name 165039071 Tissue Name 165039071
Daoy- 0.0 Ca Ski-Cervical epidermoid 0.0 Medulloblastoma carcinoma
(metastasis) TE671- 0.0 ES-2-Ovarian clear cell 0.0 Medulloblastoma
carcinoma D283 Med- 0.0 Ramos-Stimulated with 2.3 Medulloblastoma
PMA/ionomycin 6 h PFSK-1-Primitive 0.0 Ramos-Stimulated with 0.0
Neuroectodermal PMA/ionomycin 14 h XF-498-CNS 0.0 MEG-01-Chronic
0.0 myelogenous leukemia (megokaryoblast) SNB-78-Giloma 0.0
Raji-Burkitt's lymphoma 0.0 SF-268-Glioblastoma 0.0 Daudi-Burkitt's
lymphoma 0.0 T98G-Glioblastoma 0.0 U266-B-cell plasmacytoma 0.0
SK-N-SH 0.0 CA46-Burkitt's lymphoma 0.0 Neuroblastoma (metastasis)
SF-295-Glioblastoma 0.0 RL-non-Hodgkin's B-cell 0.0 lymphoma
Cerebellum 0.0 JM1-pre-B-cell lymphoma 0.0 Cerebellum 0.0 Jurkat-T
cell leukemia 0.0 NCI-H292- 0.0 TF-1-Erythroleukemia 0.0
Mucoepidermoid lung carcinoma DMS-114-Small cell 0.0 HUT 78-T-cell
lymphoma 0.0 lung cancer DMS-79-Small cell 0.0 U937-Histiocytic 0.0
lung cancer lymphoma NCI-H146-Small cell 0.0 KU-812-Myelogenous 0.0
lung cancer leukemia NCI-H526-Small cell 0.0 769-P-Clear cell renal
0.0 lung cancer carcinoma NCI-N417-Small cell 0.0 Caki-2-Clear cell
renal 0.0 lung cancer carcinoma NCI-H82-Small cell 0.0 SW 839-Clear
cell renal 0.0 lung cancer carcinoma NCI-H157-Squamous 0.0
G401-Wilms' tumor 0.0 cell lung cancer (metastasis) NCI-H1155-Large
cell 0.0 Hs766T-Pancreatic 0.0 lung cancer carcinoma (LN
metastasis) NCI-H1299-Large cell 0.0 CAPAN-1-Pancreatic 0.0 lung
cancer adenocarcinoma (liver metastasis) NCI-H727-Lung 0.0
SU86.86-Pancreatic 0.0 carcinoid carcinoma (liver metastasis)
NCI-UMC-11-Lung 0.0 BxPC-3-Pancreatic 0.0 carcinoid adenocarcinoma
LX-1-Small cell lung 0.0 HPAC-Pancreatic 0.0 cancer adenocarcinoma
Colo-205-Colon 0.0 MIA PaCa-2-Pancreatic 0.0 cancer carcinoma
KM12-Colon cancer 0.0 CFPAC-1-Pancreatic ductal 0.0 adenocarcinoma
KM20L2-Colon cancer 0.0 PANC-1-Pancreatic 0.0 epithelioid ductal
carcinoma NCI-H716-Colon 0.0 T24-Bladder carcinma 0.0 cancer
(transitional cell) SW-48-Colon 100.0 5637-Bladder carcinoma 0.0
adenocarcinoma SW1116-Colon 0.0 HT-1197-Bladder 0.0 adenocarcinoma
carcinoma LS 174T-Colon 79.6 UM-UC-3-Bladder 0.0 adenocarcinoma
carcinma (transitional cell) SW-948-Colon 0.0 A204-Rhabdomyosarcoma
0.0 adenocarcinoma SW-480-Colon 0.0 HT-1080-Fibrosarcoma 0.0
adenocarcinoma NCI-SNU-5-Gastric 0.0 MG-63-Osteosarcoma 0.0
carcinoma KATO III-Gastric 4.2 SK-LMS-1- 0.0 carcinoma
Leiomyosarcoma (vulva) NCI-SNU-16-Gastric 0.0 SJRH30- 0.0 carcinoma
Rhabdomyosarcoma (met to bone marrow) NCI-SNU-1-Gastric 0.0
A431-Epidermoid 0.0 carcinoma carcinoma RF-1-Gastric 0.0
WM266-4-Melanoma 0.0 adenocarcinoma RF-48-Gastric 0.0 DU
145-Prostate carcinoma 0.0 adenocarcinoma (brain metastasis)
MKN-45-Gastric 0.0 MDA-MB-468-Breast 0.0 carcinoma adenocarcinoma
NCI-N87-Gastric 0.0 SCC-4-Squamous cell 0.0 carcinoma carcinoma of
tongue OVCAR-5-Ovarian 0.0 SCC-9-Squamous cell 0.0 carcinoma
carcinoma of tongue RL95-2-Uterine 0.0 SCC-15-Squamous cell 0.0
carcinoma carcinoma of tongue HelaS3-Cervical 0.0 CAL 27-Squamous
cell 0.0 adenocarcinoma carcinoma of tongue
[0667] TABLE-US-00167 TABLE KM Panel 4.1D Rel. Rel. Rel. Rel.
Exp.(%) Exp.(%) Exp.(%) Exp.(%) Ag4269, Ag5115, Ag4269, Ag5115, Run
Run Run Run Tissue Name 182243380 226444771 Tissue Name 182243380
226444771 Secondary Th1 act 0.4 0.0 HUVEC IL-1beta 0.0 0.0
Secondary Th2 act 0.4 0.0 HUVEC IFN 0.1 0.0 gamma Secondary Tr1 act
0.0 0.0 HUVEC TNF 0.0 0.0 alpha + IFN gamma Secondary Th1 rest 0.0
0.0 HUVEC TNF 0.0 0.0 alpha + IL4 Secondary Th2 rest 0.1 0.0 HUVEC
IL-11 0.2 0.0 Secondary Tr1 rest 0.2 0.0 Lung 0.2 0.0 Microvascular
EC none Primary Th1 act 0.3 0.0 Lung 0.0 0.0 Microvascular EC TNF
alpha + IL- 1beta Primary Th2 act 0.3 0.0 Microvascular 0.1 0.0
Dermal EC none Primary Tr1 act 0.1 0.0 Microvascular 0.0 0.0 Dermal
EC TNF alPha + IL- 1beta Primary Th1 rest 0.1 0.0 Bronchial 0.0 0.0
epithelium TNF alpha + IL1beta Primary Th2 rest 0.1 0.0 Small
airway 0.0 0.0 epithelium none Primary Tr1 rest 0.2 0.0 Small
airway 0.0 0.0 epithelium TNF alpha + IL- 1beta CD45RA CD4 0.0 0.0
Coronery artery 0.1 0.0 lymphocyte act SMC rest CD45RO CD4 0.5 0.0
Coronery artery 0.0 0.0 lymphocyte act SMC TNF alpha + IL- 1beta
CD8 lymphocyte 0.4 0.0 Astrocytes rest 0.0 0.0 act Secondary CD8
0.5 0.0 Astrocytes 0.0 0.0 lymphocyte rest TNF alpha + IL- 1beta
Secondary CD8 1.1 0.0 KU-812 0.0 0.0 lymphocyte act (Basophil) rest
CD4 lymphocyte 0.1 0.0 KU-812 0.0 0.0 none (Basophil) PMA/ionomycin
2ry 0.0 0.0 CCD1106 0.0 0.0 Th1/Th2/Tr1_anti- (Keratinocytes) CD95
CH11 none LAK cells rest 0.1 0.0 CCD1106 0.0 0.0 (Keratinocytes)
TNF alpha + IL- 1beta LAK cells IL-2 0.4 0.0 Liver cirrhosis 26.4
20.3 LAK cells IL- 0.2 0.0 NCI-H292 none 0.0 0.0 2 + IL-12 LAK
cells IL- 0.3 0.0 NCI-H292 IL-4 0.0 0.0 2 + IFN gamma LAK cells
IL-2 + IL- 0.4 0.0 NCI-H292 IL-9 0.1 0.0 18 LAK cells 0.5 0.0
NCI-H292 IL-13 0.0 0.0 PMA/ionomycin NK Cells IL-2 rest 0.4 0.0
NCI-H292 IFN 0.0 0.0 gamma Two Way MLR 3 0.0 0.0 HPAEC none 0.0 0.0
day Two way MLR 5 0.1 0.0 HPAEC TNF 0.0 0.0 day alpha + IL-1beta
Two Way MLR 7 0.1 0.0 Lung fibroblast 0.1 0.0 day none PBMC rest
0.0 0.0 Lung fibroblast 0.3 0.1 TNF alpha + IL- 1beta PBMC PWM 0.5
0.0 Lung fibroblast 0.0 0.0 IL-4 PBMC PHA-L 0.4 0.0 Lung fibroblast
0.1 0.1 IL-9 Ramos (B cell) 0.3 0.0 Lung fibroblast 0.1 0.1 none
IL-13 Ramos (B cell) 0.0 0.0 Lung fibroblast 0.1 0.0 ionomycin IFN
gamma B lymphocytes 0.5 0.0 Dermal fibroblast 0.0 0.0 PWM CCD1070
rest B lymphocytes 0.0 0.0 Dermal fibroblast 0.3 0.0 CD40L and IL-4
CCD1070 TNF alpha EOL-1 dbcAMP 0.1 0.0 Dermal fibroblast 0.0 0.0
CCD1070 IL- 1beta EOL-1 dbcAMP 0.0 0.0 Dermal fibroblast 0.6 0.2
PMA/ionomycin IFN gamma Dendritic cells 0.0 0.0 Dermal fibroblast
0.1 0.1 none IL-4 Dendritic cells LPS 0.0 0.0 Dermal 0.9 0.4
Fibroblasts rest Dendritic cells 0.0 0.0 Neutrophils 0.5 0.1
anti-CD40 TNFa + LPS Monocytes rest 0.0 0.0 Neutrophils rest 0.3
0.4 Monocytes LPS 0.0 0.0 Colon 0.8 0.5 Macrophages rest 0.0 0.0
Lung 1.8 1.1 Macrophages LPS 0.0 0.0 Thymus 8.8 8.1 HUVEC none 0.0
0.0 Kidney 100.0 100.0 HUVEC starved 0.0 0.0
[0668] TABLE-US-00168 TABLE KN Panel 4D Rel. Exp.(%) Rel. Exp.(%)
Ag3374, Run Ag3374, Run Tissue Name 165296618 Tissue Name 165296618
Secondary Th1 act 0.0 HUVEC IL-1beta 0.0 Secondary Th2 act 0.0
HUVEC IFN gamma 0.0 Secondary Tr1 act 0.0 HUVEC TNF alpha + IFN 0.0
gamma Secondary Th1 rest 0.0 HUVEC TNF alpha + IL4 0.0 Secondary
Th2 rest 0.0 HUVEC IL-11 0.0 Secondary Tr1 rest 0.0 Lung
Microvascular EC 0.0 none Primary Th1 act 0.0 Lung Microvascular EC
0.0 TNF alpha + IL-1beta Primary Th2 act 0.0 Microvascular Dermal
0.0 EC none Primary Tr1 act 0.0 Microsvasular Dermal 0.0 EC TNF
alpha + IL-1beta Primary Th1 rest 0.0 Bronchial epithelium 0.0 TNF
alpha + IL1beta Primary Th2 rest 0.0 Small airway epithelium 0.0
none Primary Tr1 rest 0.0 Small airway epithelium 0.0 TNF alpha +
IL-1beta CD45RA CD4 0.0 Coronery artery SMC 0.0 lymphocyte act rest
CD45RO CD4 0.0 Coronery artery SMC 0.0 lymphocyte act TNF alpha +
IL-1beta CD8 lymphocyte act 0.0 Astrocytes rest 0.0 Secondary CD8
0.0 Astrocytes TNF alpha + IL- 0.0 lymphocyte rest 1beta Secondary
CD8 0.0 KU-812 (Basophil) rest 0.0 lymphocyte act CD4 lymphocyte
none 0.0 KU-812 (Basophil) 0.0 PMA/ionomycin 2ry Th1/Th2/Tr1_anti-
0.0 CCD1106 0.0 CD95 CH11 (Keratinocytes) none LAK cells rest 0.0
CCD1106 0.0 (Keratinocytes) TNF alpha + IL-1beta LAK cells IL-2 0.0
Liver cirrhosis 11.6 LAK cells IL-2 + IL-12 0.0 Lupus kidney 0.7
LAK cells IL-2 + IFN 0.0 NCI-H292 none 0.0 gamma LAK cells IL-2 +
IL-18 0.0 NCI-H292 IL-4 0.0 LAK cells 0.0 NCI-H292 IL-9 0.0
PMA/ionomycin NK Cells IL-2 rest 0.0 NCI-H292 IL-13 0.0 Two Way MLR
3 day 0.0 NCI-H292 IFN gamma 0.0 Two Way MLR 5 day 0.0 HPAEC none
0.0 Two Way MLR 7 day 0.0 HPAEC TNF alpha + IL- 0.0 1beta PBMC rest
0.0 Lung fibroblast none 0.0 PBMC PWM 0.0 Lung fibroblast TNF 0.0
alpha + IL-1beta PBMC PHA-L 0.0 Lung fibroblast IL-4 0.0 Ramos (B
cell) none 0.0 Lung fibroblast IL-9 0.0 Ramos (B cell) 0.0 Lung
fibroblast IL-13 0.0 ionomycin B lymphocytes PWM 0.0 Lung
fibroblast IFN 0.0 gamma B lymphocytes CD40L 0.0 Dermal fibroblast
0.0 and IL-4 CCD1070 rest EOL-1 dbcAMP 0.0 Dermal fibroblast 0.0
CCD1070 TNF alpha EOL-1 dbcAMP 0.0 Dermal fibroblast 0.0
PMA/ionomycin CCD1070 IL-1beta Dendritic cells none 0.0 Dermal
fibroblast IFN 0.0 gamma Dendritic cells LPS 0.0 Dermal fibroblast
IL-4 0.0 Dendritic cells anti- 0.0 IBD Colitis 2 0.0 CD40 Monocytes
rest 0.0 IBD Crohn's 0.0 Monocytes LPS 0.0 Colon 0.0 Macrophages
rest 0.0 Lung 0.0 Macrophages LPS 0.0 Thymus 100.0 HUVEC none 0.0
Kidney 0.0 HUVEC starved 0.0
[0669] TABLE-US-00169 TABLE KO General oncology screening
panel_v_2.4 Rel. Rel. Exp.(%) Exp.(%) Ag5115, Ag5115, Run Run
Tissue Name 260280407 Tissue Name 260280407 Colon cancer 1 0.0
Bladder cancer NAT 2 0.0 Colon cancer 0.0 Bladder cancer NAT 3 0.0
NAT 1 Colon cancer 2 0.0 Bladder cancer NAT 4 0.0 Colon cancer 0.0
Adenocarcinoma of the 0.0 NAT 2 prostate 1 Colon cancer 3 0.1
Adenocarcinoma of the 0.0 prostate 1 Colon cancer 0.1
Adenocarcinoma of the 0.0 NAT 3 prostate 3 Colon malignant 0.0
Adenocarcinoma of the 0.0 cancer 4 prostate 4 Colon normal 0.0
Prostate cancer NAT 5 0.0 adjacent tissue 4 Lung cancer 1 0.0
Adenocarcinoma of the 0.0 prostate 6 Lung NAT 1 0.0 Adenocarcinoma
of the 0.0 prostate 7 Lung cancer 2 0.0 Adenocarcinoma of the 0.0
prostate 8 Lung NAT 2 0.0 Adenocarcinoma of the 0.0 prostate 9
Squamous cell 0.0 Prostate cancer NAT 0.0 carcinoma 3 10 Lung NAT 3
0.0 Kidney cancer 1 0.0 metastatic 0.0 KidneyNAT 1 4.4 melanoma 1
Melanoma 2 0.0 Kidney cancer 2 2.0 Melanoma 3 0.0 Kidney NAT 2
100.0 metastatic 0.0 Kidney cancer 3 0.0 melanoma 4 metastatic 0.0
Kidney NAT 3 24.3 melanoma 5 Bladder cancer 1 0.0 Kidney cancer 4
0.0 Bladder cancer 0.0 Kidney NAT 4 12.9 NAT 1 Bladder cancer 2
0.0
[0670] CNS_neurodegeneration_v1.0 Summary: Ag4269/Ag5115 These
panels do not show differential expression of this gene in
Alzheimer's disease. However, this expression profile shows that
this gene is expressed at low levels in the CNS, including the
hippocampus and cortex. Therefore, therapeutic modulation of the
expression or function of this gene may be useful in the treatment
of neurologic disorders, such as Alzheimer's disease, Parkinson's
disease, schizophrenia, multiple sclerosis, stroke and
epilepsy.
[0671] General_screening panel_v1.4 Summary: Ag4269 Highest
expression is seen in fetal liver (CT=25). Moderate to low levels
of expression are seen in liver, fetal kidney, and cell lines
derived from colon and liver cancer. This expression is in
agreement with expression in Panel 1.3D, where expression is seen
in kidney and liver derived tissues. Thus, expression of this gene
could be used as a marker of these tissues.
[0672] General_screening_panel_v1.5 Summary: Ag5115 Highest
expression of the NOV12E gene is seen in fetal liver (CT=25.2) and
liver. Moderate levels of expression are seen in the whole brain, a
colon cancer cell line and fetal kidney. Low but significant levels
of expression are seen in the hippocampus and fetal lung. This
expression is in agreement with expression seen in other panels.
However, the NOV12E gene is also detected in fetal lung. Ag5116
This experiment shows low/undetectable levels (CTs>35) of
expression in all samples on this panel (data not shown).
[0673] Panel 1.3D Summary: Ag3374 Expression of this gene is
restricted to a few samples, with highest expression in liver
(CT=24.1), fetal liver, and kidney. Moderate expression is seen in
fetal kidney and low levels of expression are seen in a colon
cancer cell line. This expression profile suggests that this gene
could be used to differentiate between liver and other samples on
this panel and as a marker of liver and kidney tissue.
[0674] Panel 2.2 Summary: See Panel 2D for discussion. Panel 2.2
confirms the results in 2D.
[0675] Panel 2D Summary: Ag3374 Highest expression of this gene is
seen in liver derived tissue (CT=23.9), with expression in this
panel restricted to liver and kidney derived tissue. This
expression is in agreement with expression seen in Panel 1.3D. In
addition, this gene is more highly expressed in kidney tissue when
compared to normal adjacent tissue. This gene encodes a putative
kininogen, which has been shown to inhibit angiogenesis (Colman R.
Blood. 95:543; Guo Y. Arterioscler Thromb Vasc Biol. September
2001, pg. 1427). The expressed protein can also be used in the
treatment of kidney cancers as it is not expressed in kidney
cancers compared to the adjacent normal tissues and inhibition of
its activity using antibodies or small molecule drugs may be useful
in treating liver cancer. Thus, therapeutic modulation of the
expression or function of this gene could be effective in the
treatment of liver and kidney cancers.
[0676] Panel 3D Summary: Ag3374 Expression in this panel is
restricted to samples derived from colon cancer cell lines
(CTs=34-35). Thus, expression of this gene could be used to
differentiate between this sample and other samples on this panel
and as a marker to detect the presence of colon cancer.
Furthermore, therapeutic modulation of the expression or function
of this gene may be effective in the treatment of colon cancer. A
second experiment with probe and primer set Ag4269 shows
low/undetectable levels of expression (CTs>35). (Data not
shown.)
[0677] Panel 4.1D Summary: Ag5115/Ag4269 Two experiments with two
different probe and primer sets are in good agreement with highest
expression of the NOV12E in the kidney (CTs=27). In addition,
moderate levels of expression of this gene are also seen in thymus,
lung and colon. The probe and primer sets for Ag5115 are specific
to NOV12E. In a second experiment with Ag4269 low levels of
expression of this gene is also seen in selected samples, including
T cells, neutrophils, and activated dermal fibroblasts.
[0678] Panel 4D Summary: Ag3374 This transcript is most highly
expressed in the thymus (CT=24.3). The protein encoded by this gene
could therefore play an important role in T cell development. Thus,
therapeutic modulation of the expression or function of this gene
may modulate immune function (T cell development) and be important
for organ transplant, AIDS treatment or post chemotherapy immune
reconstitution.
[0679] In addition, moderate levels of expression are seen in liver
cirrhosis and lupus kidney, in agreement with previous panels that
showed expression in liver and kidney derived tissues.
[0680] General oncology screening panel_v.sub.--2.4 Summary: Ag5115
Expression of the NOV12E is restricted to kidney-derived tissue
(highest CT=26). In addition, expression is higher in normal tissue
than in adjacent tumor. Thus, expression of this gene could be used
as a marker of kidney tissue. Furthermore, therapeutic modulation
of this putative kininogen may be effective in the treatment of
kidney cancer as a protein therapeutic. Ag5116 This experiment
shows low/undetectable levels (CTs>35) of expression in all
samples on this panel (data not shown).
[0681] L. NOV13A: Serine Protease-CUB Domain Protein
[0682] Expression of gene NOV13A, representing a full-length
physical clone, was assessed using the primer-probe set Ag6855,
described in Table LA. Results of the RTQ-PCR runs are shown in
Table LB. TABLE-US-00170 TABLE LA Probe Name Ag6855 Start SEQ ID
Primers Sequences Length Position No Forward
5'-ctttacttcatgcacttcaacttg-3' 24 403 181 Probe
TET-5'-cctcctacctttgtgaatatgactatgtga- 30 431 182 3'-TAMRA Reverse
5'-actctcgaagtgtcctcagtttc-3' 23 466 183
[0683] TABLE-US-00171 TABLE LB General_screening_panel_v1.6 Rel.
Exp.(%) Rel. Exp.(%) Ag6855, Ag6855, Run Run Tissue Name 278020605
Tissue Name 278020605 Adipose 0.0 Renal ca. TK-10 10.6 Melanoma*
23.3 Bladder 0.0 Hs688(A).T Melanoma* 22.7 Gastric ca. (liver met.)
0.0 Hs688(B).T NCI-N87 Melanoma* M14 0.0 Gastric ca. KATO III 0.0
Melanoma* 0.0 Colon ca. SW-948 0.0 LOXIMVI Melanoma* SK- 0.0 Colon
ca. SW480 0.0 MEL-5 Squamous cell 0.0 Colon ca.* (SW480 0.0
carcinoma SCC-4 met) SW620 Testis Pool 0.0 Colon ca. HT29 0.0
Prostate ca.* (bone 0.0 Colon ca. HCT-116 0.0 met) PC-3 Prostate
Pool 7.0 Colon ca. CaCo-2 0.0 Placenta 0.0 Colon cancer tissue 0.0
Uterus Pool 27.4 Colon ca. SW1116 0.0 Ovarian ca. 0.0 Colon ca.
Colo-205 0.0 OVCAR-3 Ovarian ca. SK- 0.0 Colon ca. SW-48 0.0 OV-3
Ovarian ca. 0.0 Colon Pool 37.1 OVCAR-4 Ovarian ca. 0.0 Small
Intestine Pool 77.9 OVCAR-5 Ovarian ca. 0.0 Stomach Pool 16.0
IGROV-1 Ovarian ca. 0.0 Bone Marrow Pool 23.0 OVCAR-8 Ovary 5.8
Fetal Heart 73.2 Breast ca. MCF-7 0.0 Heart Pool 43.8 Breast ca.
MDA- 0.0 Lymph Node Pool 41.5 MB-231 Breast ca. BT 549 0.0 Fetal
Skeletal Muscle 11.5 Breast ca. T47D 0.0 Skeletal Muscle Pool 9.5
Breast ca. MDA-N 0.0 Spleen Pool 0.0 Breast Pool 27.5 Thymus Pool
22.7 Trachea 9.9 CNS cancer 0.0 (glio/astro) U87-MG Lung 0.0 CNS
cancer 47.3 (glio/astro) U-118-MG Fetal Lung 8.8 CNS cancer 0.0
(neuro; met) SK-N-AS Lung ca. NCI-N417 0.0 CNS cancer (astro) 0.0
SF-539 Lung ca. LX-1 0.0 CNS cancer (astro) 0.0 SNB-75 Lung ca.
NCI-H146 0.0 CNS cancer (glio) 0.0 SNB-19 Lung ca. SHP-77 0.0 CNS
cancer (glio) SF- 32.1 295 Lung ca. A549 0.0 Brain (Amygdala) 0.0
Pool Lung ca. NCI-H526 0.0 Brain (cerebellum) 21.3 Lung ca. NCI-H23
0.0 Brain (fetal) 46.0 Lung ca. NCI-H460 0.0 Brain (Hippocampus)
14.0 Pool Lung ca. HOP-62 0.0 Cerebral Cortex Pool 4.9 Lung ca.
NCI-H522 0.0 Brain (Substantia 6.3 nigra) Pool Liver 94.0 Brain
(Thalamus) pool 7.2 Fetal Liver 100.0 Brain (whole) 9.9 Liver ca.
HepG2 25.7 Spinal Cord Pool 46.7 Kidney Pool 86.5 Adrenal Gland
10.9 Fetal Kidney 0.0 Pituitary gland Pool 0.0 Renal ca. 786-0 0.0
Salivary Gland 0.0 Renal ca. A498 0.0 Thyroid (female) 0.0 Renal
ca. ACHN 0.0 Pancreatic ca. 0.0 CAPAN2 Renal ca. UO-31 0.0 Pancreas
Pool 0.0
[0684] General_screening panel_v1.6 Summary: Ag6855 Expression of
the NOV13A gene is limited to the fetal liver (CT=34.9). Thus,
expression of this gene may be used as a marker of this tissue.
[0685] M. NOV14A: Hemopexin
[0686] Expression of gene NOV14A, representing a full-length
physical clone, was assessed using the primer-probe set Ag6949,
described in Table MA. Results of the RTQ-PCR runs are shown in
Table MB. TABLE-US-00172 TABLE MA Probe Name Ag6949 Start SEQ ID
Primers Sequences Length Position No Forward
5'-ttttaaagggacccactactgg-3' 22 625 184 Probe
TET-5'-ctggcatagctggcccattgctcat-3'- 25 577 185 TAMRA Reverse
5'-gaaaaggcagcatccactg-3' 19 536 186
[0687] TABLE-US-00173 TABLE MB General_screening_panel_v1.6 Rel.
Exp.(%) Rel. Exp.(%) Ag6949, Ag6949, Run Run Tissue Name 279032765
Tissue Name 279032765 Adipose 0.0 Renal ca. TK-10 0.2 Melanoma* 0.0
Bladder 0.2 Hs688(A).T Melanoma* 0.1 Gastric ca. (liver met.) 0.1
Hs688(B).T NCI-N87 Melanoma* M14 0.1 Gastric ca. KATO III 0.0
Melanoma* 0.0 Colon ca. SW-948 0.0 LOXIMVI Melanoma* SK- 0.0 Colon
ca. SW480 0.0 MEL-5 Squamous cell 0.0 Colon ca.* (SW480 0.1
carcinoma SCC-4 met) SW620 Testis Pool 0.1 Colon ca. HT29 0.0
Prostate ca.* (bone 0.1 Colon ca. HCT-116 0.2 met) PC-3 Prostate
Pool 0.1 Colon ca. CaCo-2 3.3 Placenta 0.0 Colon cancer tissue 0.1
Uterus Pool 0.0 Colon ca. SW1116 0.0 Ovarian ca. 0.1 Colon ca.
Colo-205 0.0 OVCAR-3 Ovarian ca. SK- 0.1 Colon ca. SW-48 0.0 OV-3
Ovarian ca. 0.0 Colon Pool 0.1 OVCAR-4 Ovarian ca. 0.5 Small
Intestine Pool 0.1 OVCAR-5 Ovarian ca. 0.0 Stomach Pool 0.1 IGROV-1
Ovarian ca. 0.0 Bone Marrow Pool 0.0 OVCAR-8 Ovary 0.1 Fetal Heart
0.1 Breast ca. MCF-7 0.3 Heart Pool 0.0 Breast ca. MDA- 0.0 Lymph
Node Pool 0.1 MB-231 Breast ca. BT 549 0.1 Fetal Skeletal Muscle
0.0 Breast ca. T47D 0.2 Skeletal Muscle Pool 0.0 Breast ca. MDA-N
0.0 Spleen Pool 0.0 Breast Pool 0.1 Thymus Pool 0.1 Trachea 0.1 CNS
cancer 0.0 (glio/astro) U87-MG Lung 0.1 CNS cancer 0.1 (glio/astro)
U-118-MG Fetal Lung 0.4 CNS cancer 0.1 (neuro; met) SK-N-AS Lung
ca. NCI-N417 0.0 CNS cancer (astro) 0.0 SF-539 Lung ca. LX-1 0.0
CNS cancer (astro) 0.2 SNB-75 Lung ca. NCI-H146 0.0 CNS cancer
(glio) 0.0 SNB-19 Lung ca. SHP-77 0.0 CNS cancer (glio) SF- 0.2 295
Lung ca. A549 0.1 Brain (Amygdala) 0.0 Pool Lung ca. NCI-H526 0.0
Brain (cerebellum) 0.4 Lung ca. NCI-H23 0.1 Brain (fetal) 0.4 Lung
ca. NCI-H460 0.0 Brain (Hippocampus) 0.0 Pool Lung ca. HOP-62 0.1
Cerebral Cortex Pool 0.0 Lung ca. NCI-H522 0.0 Brain (Substantia
0.0 nigra) Pool Liver 100.0 Brain (Thalamus) pool 0.0 Fetal Liver
87.7 Brain (whole) 1.7 Liver ca. HepG2 0.2 Spinal Cord Pool 0.0
Kidney Pool 0.2 Adrenal Gland 0.0 Fetal Kidney 0.1 Pituitary gland
Pool 0.0 Renal ca. 786-0 0.0 Salivary Gland 0.0 Renal ca. A498 0.0
Thyroid (female) 0.0 Renal ca. ACHN 0.0 Pancreatic ca. 0.0 CAPAN2
Renal ca. UO-31 0.1 Pancreas Pool 0.0
[0688] General_screening_panel_v1.6 Summary: Ag6949 Highest
expression of the NOV14A gene is seen in the liver (CT=23). This
gene encodes a homolog of hemopexin, a heme binding glycoprotein
synthesized in the liver that has been implicated in the transport
of heme into liver cells. Thus, expression of this gene could be
used as a marker of liver tissue and to differentiate these liver
derived samples from other samples on this panel.
[0689] Orthologues of hemopexin appear to be upregulated in
hepatocellular carcinoma cells infected with woodchuck hepatitis B
(Darabi A. Cancer Lett 1995 Aug. 16;95(1-2): 153-9). Thus, based on
the preferential expression of this gene in liver and the homology
of this gene to hemopexin, therapeutic modulation of the expression
or function of this gene may be effective in the treatment of liver
cancer.
[0690] N. NOV15A: F2 Alpha Prostoglandin Regulatory PROTEIN
[0691] Expression of gene NOV15A was assessed using the
primer-probe set Ag4383, described in Table NA. Results of the
RTQ-PCR runs are shown in Tables NB, NC, ND and NE. TABLE-US-00174
TABLE NA Probe Name Ag4383 Start SEQ ID Primers Sequences Length
Position No Forward 5'-agaccaaggccactacaaatgt-3' 22 350 187 Probe
TET-5'-cacagatgccactgtccagggaa-3'- 23 383 188 TAMRA Reverse
5'-acctgcactgtgtcctcatagt-3' 22 406 189
[0692] TABLE-US-00175 TABLE NB CNS_neurodegeneration_v1.0 Rel.
Exp.(%) Rel. Exp.(%) Ag4383, Ag4383, Run Run Tissue Name 224502235
Tissue Name 224502235 AD 1 Hippo 12.9 Control (Path) 3 7.0 Temporal
Ctx AD 2 Hippo 23.8 Control (Path) 4 34.9 Temporal Ctx AD 3 Hippo
3.4 AD 1 Occipital Ctx 7.4 AD 4 Hippo 6.1 AD 2 Occipital Ctx 0.0
(Missing) AD 5 Hippo 67.4 AD 3 Occipital Ctx 2.7 AD 6 Hippo 41.8 AD
4 Occipital Ctx 19.5 Control 2 Hippo 22.8 AD 5 Occipital Ctx 46.7
Control 4 Hippo 16.5 AD 6 Occipital Ctx 9.7 Control (Path) 3 6.7
Control 1 Occipital 3.7 Hippo Ctx AD 1 Temporal 16.0 Control 2
Occipital 46.3 Ctx Ctx AD 2 Temporal 17.0 Control 3 Occipital 12.8
Ctx Ctx AD 3 Temporal 5.8 Control 4 Occipital 8.2 Ctx Ctx AD 4
Temporal 19.5 Control (Path) 1 83.5 Ctx Occipital Ctx AD 5 Inf
Temporal 72.7 Control (Path) 2 7.1 Ctx Occipital Ctx AD 5 Sup 31.2
Control (Path) 3 1.6 Temporal Ctx Occipital Ctx AD 6 Inf Temporal
38.2 Control (Path) 4 10.8 Ctx Occipital Ctx AD 6 Sup 47.6 Control
1 Parietal 8.7 Temporal Ctx Ctx Control 1 9.8 Control 2 Parietal
36.9 Temporal Ctx Ctx Control 2 59.5 Control 3 Parietal 15.8
Temporal Ctx Ctx Control 3 9.7 Control (Path) 1 100.0 Temporal Ctx
Parietal Ctx Control 3 16.3 Control (Path) 2 18.3 Temporal Ctx
Parietal Ctx Control (Path) 1 67.8 Control (Path) 3 5.5 Temporal
Ctx Parietal Ctx Control (Path) 2 44.1 Control (Path) 4 45.1
Temporal Ctx Parietal Ctx
[0693] TABLE-US-00176 TABLE NC General_screening_panel_v1.4 Rel.
Exp.(%) Rel. Exp.(%) Ag4383, Ag4383, Run Run Tissue Name 222567780
Tissue Name 222567780 Adipose 1.0 Renal ca. TK-10 12.2 Melanoma*
10.4 Bladder 4.8 Hs688(A).T Melanoma* 11.9 Gastric ca. (liver met.)
7.3 Hs688(B).T NCI-N87 Melanoma* M14 31.6 Gastric ca. KATO III 24.8
Melanoma* 0.0 Colon ca. SW-948 5.5 LOXIMVI Melanoma* SK- 4.1 Colon
ca. SW480 11.3 MEL-5 Squamous cell 16.4 Colon ca.* (SW480 3.9
carcinoma SCC-4 met) SW620 Testis Pool 2.0 Colon ca. HT29 3.4
Prostate ca.* (bone 1.3 Colon ca. HCT-116 16.4 met) PC-3 Prostate
Pool 1.7 Colon ca. CaCo-2 2.8 Placenta 5.3 Colon cancer tissue 8.2
Uterus Pool 1.7 Colon ca. SW1116 3.7 Ovarian ca. 10.2 Colon ca.
Colo-205 3.0 OVCAR-3 Ovarian ca. SK- 9.0 Colon ca. SW-48 6.9 OV-3
Ovarian ca. 3.4 Colon Pool 8.0 OVCAR-4 Ovarian ca. 15.8 Small
Intestine Pool 7.5 OVCAR-5 Ovarian ca. 10.2 Stomach Pool 4.1
IGROV-1 Ovarian ca. 10.0 Bone Marrow Pool 2.5 OVCAR-8 Ovary 5.1
Fetal Heart 3.7 Breast ca. MCF-7 3.7 Heart Pool 5.0 Breast ca. MDA-
0.4 Lymph Node Pool 11.3 MB-231 Breast ca. BT 549 0.3 Fetal
Skeletal Muscle 2.8 Breast ca. T47D 30.8 Skeletal Muscle Pool 0.7
Breast ca. MDA-N 6.0 Spleen Pool 0.9 Breast Pool 9.0 Thymus Pool
3.5 Trachea 5.4 CNS cancer 20.7 (glio/astro) U87-MG Lung 0.2 CNS
cancer 12.9 (glio/astro) U-118-MG Fetal Lung 5.3 CNS cancer 6.8
(neuro; met) SK-N-AS Lung ca. NCI-N417 4.7 CNS cancer (astro) 17.1
SF-539 Lung ca. LX-1 7.3 CNS cancer (astro) 100.0 SNB-75 Lung ca.
NCI-H146 2.4 CNS cancer (glio) 8.7 SNB-19 Lung ca. SHP-77 6.9 CNS
cancer (glio) SF- 13.9 295 Lung ca. A549 9.3 Brain (Amygdala) 0.9
Pool Lung ca. NCI-H526 6.3 Brain (cerebellum) 0.9 Lung ca. NCI-H23
1.9 Brain (fetal) 6.7 Lung ca. NCI-H460 6.3 Brain (Hippocampus) 1.0
Pool Lung ca. HOP-62 1.7 Cerebral Cortex Pool 1.6 Lung ca. NCI-H522
0.6 Brain (Substantia 1.6 nigra) Pool Liver 0.3 Brain (Thalamus)
Pool 2.0 Fetal Liver 1.8 Brain (whole) 1.9 Liver ca. HepG2 3.4
Spinal Cord Pool 0.8 Kidney Pool 15.3 Adrenal Gland 6.2 Fetal
Kidney 1.5 Pituitary gland Pool 0.4 Renal ca. 786-0 34.4 Salivary
Gland 3.3 Renal ca. A498 7.7 Thyroid (female) 1.4 Renal ca. ACHN
3.2 Pancreatic ca. 1.5 CAPAN2 Renal ca. UO-31 15.6 Pancreas Pool
10.1
[0694] TABLE-US-00177 TABLE ND Panel CNS_1 Rel. Exp.(%) Rel.
Ag4383, Exp.(%) Ag4383, Run Run Tissue Name 190323005 Tissue Name
190323005 BA4 Control 34.2 BA17 PSP 4.4 BA4 Control2 28.9 BA17 PSP2
10.9 BA4 0.0 Sub Nigra Control 21.5 Alzheimer's2 BA4 Parkinson's
22.7 Sub Nigra Control2 24.5 BA4 50.0 Sub Nigra 6.8 Parkinson's2
Alzheimer's2 BA4 11.9 Sub Nigra 29.7 Huntington's Parkinson's2 BA4
12.4 Sub Nigra 42.3 Huntington's2 Huntington's BA4 PSP 3.3 Sub
Nigra 23.3 Huntington's2 BA4 PSP2 18.6 Sub Nigra PSP2 3.1 BA4
Depression 12.3 Sub Nigra 0.0 Depression BA4 3.4 Sub Nigra 10.6
Depression2 Depression2 BA7 Control 33.4 Glob Palladus 9.2 Control
BA7 Control2 45.4 Glob Palladus 3.4 Control2 BA7 3.1 Glob Palladus
20.7 Alzheimer's2 Alzheimer's BA7 Parkinson's 14.8 Glob Palladus
3.0 Alzheimer's2 BA7 33.2 Glob Palladus 40.1 Parkinson's2
Parkinson's BA7 30.8 Glob Palladus 11.6 Huntington's Parkinson's2
BA7 73.2 Glob Palladus PSP 1.5 Huntington's2 BA7 PSP 12.0 Glob
Palladus PSP2 6.5 BA7 PSP2 20.6 Glob Palladus 0.0 Depression BA7
Depression 0.0 Temp Pole Control 17.9 BA9 Control 20.0 Temp Pole
Control2 48.0 BA9 Control2 43.2 Temp Pole 0.0 Alzheimer's BA9 3.1
Temp Pole 2.7 Alzheimer's Alzheimer's2 BA9 9.2 Temp Pole 13.6
Alzheimer's2 Parkinson's BA9 Parkinson's 3.8 Temp Pole 36.9
Parkinson's2 BA9 41.2 Temp Pole 33.4 Parkinson's2 Huntington's BA9
36.6 Temp Pole PSP 0.0 Huntington's BA9 11.2 Temp Pole PSP2 0.0
Huntington's2 BA9 PSP 10.7 Temp Pole 3.2 Depression2 BA9 PSP2 8.0
Cing Gyr Control 100.0 BA9 Depression 2.2 Cing Gyr Control2 31.0
BA9 9.6 Cing Gyr 31.2 Depression2 Alzheimer's BA17 Control 32.5
Cing Gyr 3.5 Alzheimer's2 BA17 Control2 41.5 Cing Gyr 40.3
Parkinson's BA17 10.8 Cing Gyr 24.8 Alzheimer's2 Parkinson's2 BA17
8.7 Cing Gyr 47.6 Parkinson's Huntington's BA17 25.9 Cing Gyr 22.2
Parkinson's2 Huntington's2 BA17 37.4 Cing Gyr PSP 0.0 Huntington's
BA17 16.7 Cing Gyr PSP2 0.0 Huntington's2 BA17 5.2 Cing Gyr 6.8
Depression Depression BA17 12.1 Cing Gyr 6.4 Depression2
Depression2
[0695] TABLE-US-00178 TABLE NE Panel CNS_1.1 Rel. Exp.(%) Rel.
Ag4383, Exp.(%) Ag4383, Run Run Tissue Name 190028010 Tissue Name
190028010 Cing Gyr 7.8 BA17 PSP2 4.2 Depression2 Cing Gyr 0.0 BA17
PSP 15.8 Depression Cing Gyr PSP2 3.9 BA17 2.3 Huntington's2 Cing
Gyr PSP 16.8 BA17 30.8 Huntington's Cing Gyr 14.6 BA17 43.5
Huntington's2 Parkinson's2 Cing Gyr 46.7 BA17 11.4 Huntington's
Parkinson's Cing Gyr 26.1 BA17 8.3 Parkinson's2 Alzheimer's2 Cing
Gyr 26.4 BA17 Control2 60.7 Parkinson's Cing Gyr 29.9 BA17 Control
35.1 Alzheimer's2 Cing Gyr 12.2 BA9 0.0 Alzheimer's Depression2
Cing Gyr Control2 20.0 BA9 Depression 15.5 Cing Gyr Control 92.0
BA9 PSP2 3.5 Temp Pole 14.3 BA9 PSP 7.9 Depression2 Temp Pole PSP2
6.0 BA9 52.1 Huntington's2 Temp Pole PSP 2.3 BA9 65.1 Huntington's
Temp Pole 57.8 BA9 100.0 Huntington's Parkinson's2 Temp Pole 50.3
BA9 Parkinson's 51.4 Parkinson's2 Temp Pole 44.8 BA9 12.0
Parkinson's Alzheimer's2 Temp Pole 7.5 BA9 3.8 Alzheimer's2
Alzheimer's Temp Pole 3.8 BA9 Control2 91.4 Alzheimer's Temp Pole
Control2 48.6 BA9 Control 7.7 Temp Pole Control 22.8 BA7 Depression
4.1 Glob Palladus 0.0 BA7 PSP2 24.0 Depression Glob Palladus PSP2
0.0 BA7 PSP 21.5 Glob Palladus PSP 0.0 BA7 54.3 Huntington's2 Glob
Palladus 3.5 BA7 82.9 Parkinson's2 Huntington's Glob Palladus 83.5
BA7 42.6 Parkinson's Parkinson's2 Glob Palladus 6.5 BA7 Parkinson's
31.0 Alzheimer's2 Glob Palladus 8.5 BA7 4.1 Alzheimer's
Alzheimer's2 Glob Palladus 4.0 BA7 Control2 46.3 Control2 Glob
Palladus 3.5 BA7 Control 48.3 Control Sub Nigra 3.6 BA4 0.0
Depression2 Depression2 0.0 Sub Nigra 0.0 BA4 Depression 0.0
Depression Sub Nigra PSP2 6.1 BA4 PSP2 32.8 Sub Nigra 30.4 BA4 PSP
7.4 Huntington's2 Sub Nigra 59.5 BA4 1.6 Huntington's Huntington's2
Sub Nigra 36.9 BA4 30.6 Parkinson's2 Huntington's Sub Nigra 0.0 BA4
59.5 Alzheimer's2 Parkinson's2 Sub Nigra Control2 10.4 BA4
Parkinson's 62.0 Sub Nigra Control 40.6 BA4 11.0 Alzheimer's2 BA17
Depression2 6.0 BA4 Control2 32.5 BA17 Depression 12.1 BA4 Control
28.9
[0696] CNS_neurodegeneration_v1.0 Summary: Ag4383 This panel
confirms the expression of the NOV15A gene at low levels in the
brains of an independent group of individuals. This gene is found
to be slightly down-regulated in the temporal cortex of Alzheimer's
disease patients when analyzed by ANCOVA (p=0.0087). Therefore,
treatment with antagonists or agonists may prevent or delay the
onset of AD.
[0697] General_screening_panel_v1.4 Summary: Ag4383 Highest
expression of the NOV15A gene is detected in a CNS cancer cell line
(CT=24.5). In addition, significant expression of this gene is seen
in cluster of cancer cell lines including CNS, pancreatic, colon,
gastric, renal, lung, breast, ovarian, squamous cell carcinoma and
melanoma cancer cell lines. Therefore, therapeutic modulation of
this gene product may be beneficial in the treatment of these
cancers.
[0698] Among tissues with metabolic or endocrine function, this
gene is expressed at high to moderate levels in pancreas, adipose,
adrenal gland, thyroid, pituitary gland, skeletal muscle, heart,
liver and the gastrointestinal tract. Therefore, therapeutic
modulation of the activity of this gene may prove useful in the
treatment of endocrine/metabolically related diseases, such as
obesity and diabetes.
[0699] In addition, this gene is expressed at moderate levels in
all regions of the central nervous system examined, including
amygdala, hippocampus, substantia nigra, thalamus, cerebellum,
cerebral cortex, and spinal cord. Therefore, this gene may play a
role in central nervous system disorders such as Alzheimer's
disease, Parkinson's disease, epilepsy, multiple sclerosis,
schizophrenia and depression.
[0700] The NOV15A gene codes for a homologue of mouse F2 alpha
prostaglandin regulatory protein (FPRP). FPRP, a cell-surface Ig
superfamily protein, associates specifically with CD81 or with CD81
and CD9, but not with integrins or other TM4SF proteins (Stipp et
al., 2001, J Biol Chem 276(7):4853-62, PMID: 11087758). CD81 is a
critical regulator of neuron-induced astrocytic differentiation
(Kelic et al., 2001, Mol Cell Neurosci 17(3):551-60, PMID:
11273649). Therefore, FPRP encoded by this gene may play a role in
astrocyte differentiation and brain development.
[0701] Panel 4.1D Summary: Ag4383 Results from one experiment with
the NOV15A gene are not included. The amp plot indicates that there
were experimental difficulties with this run (data not shown).
[0702] Panel CNS.sub.--1 Summary: Ag4383 This panel confirms the
expression of the NOV15A gene at low levels in the brains of an
independent group of individuals. Please see Panel 1.4 for a
discussion of the potential utility of this gene in treatment of
central nervous system disorders.
[0703] Panel CNS.sub.--1.1 Summary: Ag4383 This panel confirms the
expression of the NOV15A gene at low levels in the brains of an
independent group of individuals. Please see Panel 1.4 for a
discussion of the potential utility of this gene in treatment of
central nervous system disorders.
[0704] O. NOV16A: Neuronal Leucine-Rich Repeat Protein
[0705] Expression of gene NOV16A was assessed using the
primer-probe sets Ag4386 and Ag6885, described in Tables OA and OB.
Results of the RTQ-PCR runs are shown in Tables OC, OD, OE and OF.
TABLE-US-00179 TABLE OA Probe Name Ag4386 Start SEQ ID Primers
Sequences Length Position No Forward 5'-tcacatgacctttgactttgtg-3'
22 1467 190 Probe TET-5'-acctggccctctggggataaaa-3'- 23 1491 191
TAMRA Reverse 5'-gaaggaaaggtcagaagagctt-3' 22 1540 192
[0706] TABLE-US-00180 TABLE OB Probe Name Ag6885 Start SEQ ID
Primers Sequences Length Position No Forward
5'-cctcaaggtgaccagtttgtc-3' 21 811 193 Probe
TET-5'-cgcccttcagacactagaggaaacag-3'- 26 771 194 TAMRA Reverse
5'-ctcctggatgtggcagataa-3' 20 751 195
[0707] TABLE-US-00181 TABLE OC CNS_neurodegeneration_v1.0 Rel.
Exp.(%) Rel. Ag4386, Exp.(%) Ag4386, Run Run Tissue Name 224502238
Tissue Name 224502238 AD 1 Hippo 6.8 Control (Path) 3 0.0 Temporal
Ctx AD 2 Hippo 11.4 Control (Path) 4 11.7 Temporal Ctx AD 3 Hippo
6.3 AD 1 Occipital 11.3 Ctx AD 4 Hippo 0.0 AD 2 Occipital 0.0 Ctx
(Missing) AD 5 hippo 100.0 AD 3 Occipital 3.0 Ctx AD 6 Hippo 24.5
AD 4 Occipital 7.7 Ctx Control 2 Hippo 10.8 AD 5 Occipital 7.2 Ctx
Control 4 Hippo 0.0 AD 6 Occipital 7.8 Ctx Control (Path) 3 0.0
Control 1 0.0 Hippo Occipital Ctx AD 1 Temporal Ctx 12.3 Control 2
33.4 Occipital Ctx AD 2 Temporal Ctx 6.3 Control 3 13.6 Occipital
Ctx AD 3 Temporal Ctx 0.0 Control 4 0.0 Occipital Ctx AD 4 Temporal
Ctx 5.8 Control (Path) 1 21.3 Occipital Ctx AD 5 Inf Temporal 37.9
Control (Path) 2 3.8 Ctx Occipital Ctx AD 5 SupTemporal 25.9
Control (Path) 3 0.0 Ctx Occipital Ctx AD 6 Inf Temporal 19.9
Control (Path) 4 4.4 Ctx Occipital Ctx AD 6 Sup Temporal 18.0
Control 1 Parietal 8.1 Ctx Ctx Control 1 Temporal 0.0 Control 2
Parietal 8.7 Ctx Ctx Control 2 Temporal 5.9 Control 3 Parietal 5.6
Ctx Ctx Control 3 Temporal 0.0 Control (Path) 1 8.9 Ctx Parietal
Ctx Control 4 Temporal 0.0 Control (Path) 2 0.0 Ctx Parietal Ctx
Control (Path) 1 7.9 Control (Path) 3 0.0 Temporal Ctx Parietal Ctx
Control (Path) 2 12.4 Control (Path) 4 11.3 Temporal Ctx Parietal
Ctx
[0708] TABLE-US-00182 TABLE OD General_screening_panel_v1.4 Rel.
Exp.(%) Rel. Exp.(%) Ag4386, Ag4386, Run Run Tissue Name 222567010
Tissue Name 222567010 Adipose 0.1 Renal ca. TK-10 0.2 Melanoma* 0.0
Bladder 1.0 Hs688(A).T Melanoma* 0.0 Gastric ca. (liver met.) 0.4
Hs688(B).T NCI-N87 Melanoma* M14 0.0 Gastric ca. KATO III 0.0
Melanoma* 0.0 Colon ca. SW-948 0.0 LOXIMVI Melanoma* SK- 0.0 Colon
ca. SW480 0.3 MEL-5 squamous cell 0.0 Colon ca.* (SW480 0.3
carcinoma SCC-4 met) SW620 Testis Pool 1.7 Colon ca. HT29 0.1
Prostate ca.* (bone 0.0 Colon ca. HCT-116 0.0 met) PC-3 Prostate
Pool 0.5 Colon ca. CaCo-2 0.0 Placenta 0.0 Colon cancer tissue 0.0
Uterus Pool 0.0 Colon ca. SW1116 0.0 Ovarian ca. 0.0 Colon ca.
Colo-205 0.1 OVCAR-3 Ovarian ca. SK- 0.0 Colon ca. SW-48 0.3 OV-3
Ovarian ca. 0.0 Colon Pool 0.1 OVCAR-4 Ovarian ca. 1.5 Small
Intestine Pool 0.2 OVCAR-5 Ovarian ca. 0.1 Stomach Pool 0.1 IGROV-1
Ovarian ca. 0.2 Bone Marrow Pool 0.1 OVCAR-8 Ovary 0.0 Fetal Heart
0.0 Breast ca. MCF-7 1.8 Heart Pool 0.1 Breast ca. MDA- 0.3 Lymph
Node Pool 0.2 MB-231 Breast ca. BT 549 0.1 Fetal Skeletal Muscle
0.9 Breast ca. T47D 2.4 Skeletal Muscle Pool 22.5 Breast ca. MDA-N
0.0 Spleen Pool 0.4 Breast Pool 0.1 Thymus Pool 0.7 Trachea 0.9 CNS
cancer 0.1 (glio/astro) U87-MG Lung 0.0 CNS cancer 0.1 (glio/astro)
U-118-MG Fetal Lung 1.6 CNS cancer 0.3 (neuro; met) SK-N-AS Lung
ca. NCI-N417 0.0 CNS cancer (astro) 0.0 SF-539 Lung ca. LX-1 0.4
CNS cancer (astro) 0.0 SNB-75 Lung ca. NCI-H146 0.0 CNS cancer
(glio) 0.0 SNB-19 Lung ca. SHP-77 0.2 CNS cancer (glio) SF- 0.0 295
Lung ca. A549 0.0 Brain (Amygdala) 0.3 Pool Lung ca. NCI-H526 0.1
Brain (cerebellum) 100.0 Lung ca. NCI-H23 0.1 Brain (fetal) 0.1
Lung ca. NCI-H460 0.1 Brain (Hippocampus) 0.1 Pool Lung ca. HOP-62
0.0 Cerebral Cortex Pool 0.0 Lung ca. NCI-H522 0.0 Brain
(Substantia 0.1 nigra) Pool Liver 0.7 Brain (Thalamus) Pool 1.1
Fetal Liver 0.2 Brain (whole) 1.6 Liver ca. HepG2 0.0 Spinal Cord
Pool 4.2 Kidney Pool 0.2 Adrenal Gland 1.4 Fetal Kidney 0.1
Pituitary gland Pool 0.9 Renal ca. 786-0 0.2 Salivary Gland 1.3
Renal ca. A498 0.0 Thyroid (female) 0.7 Renal ca. ACHN 0.1
Pancreatic ca. 0.1 CAPAN2 Renal ca. UO-31 0.1 Pancreas Pool 0.9
[0709] TABLE-US-00183 TABLE OE General_screening_panel_v1.6 Rel.
Exp.(%) Rel. Exp.(%) Ag6885, Ag6885, Run Run Tissue Name 278388126
Tissue Name 278388126 Adipose 0.5 Renal ca. TK-10 0.0 Melanoma* 0.0
Bladder 0.7 Hs688(A).T Melanoma* 0.0 Gastric ca. (liver met.) 1.0
Hs688(B).T NCI-N87 Melanoma* M14 0.0 Gastric ca. KATO III 0.0
Melanoma* 0.0 Colon ca. SW-948 0.3 LOXIMVI Melanoma* SK- 0.0 Colon
ca. SW480 0.6 MEL-5 Squamous cell 0.0 Colon ca.* (SW480 0.1
carcinoma SCC-4 met) SW620 Testis Pool 2.8 Colon ca. HT29 0.1
Prostate ca.* (bone 0.0 Colon ca. HCT-116 0.0 met) PC-3 Prostate
Pool 0.7 Colon ca. CaCo-2 0.0 Placenta 0.0 Colon cancer tissue 0.0
Uterus Pool 0.0 Colon ca. SW1116 0.0 Ovarian ca. 0.1 Colon ca.
Colo-205 0.1 OVCAR-3 Ovarian ca. SK- 0.1 Colon ca. SW-48 0.0 OV-3
Ovarian ca. 0.1 Colon Pool 0.1 OVCAR-4 Ovarian ca. 0.8 Small
Intestine Pool 0.3 OVCAR-5 OVarian ca. 0.0 Stomach Pool 0.4 IGROV-1
Ovarian ca. 0.1 Bone Marrow Pool 0.3 OVCAR-8 Ovary 0.1 Fetal Heart
0.2 Breast ca. MCF-7 0.9 Heart Pool 0.5 Breast ca. MDA- 0.0 Lymph
Node Pool 0.1 MB-231 Breast ca. BT 549 0.1 Fetal Skeletal Muscle
1.1 Breast ca. T47D 1.0 Skeletal Muscle Pool 8.2 Breast ca. MDA-N
0.0 Spleen Pool 0.5 Breast Pool 0.2 Thymus Pool 1.5 Trachea 1.0 CNS
cancer 0.0 (glio/astro) U87-MG Lung 0.0 CNS cancer 0.2 (glio/astro)
U-118-MG Fetal Lung 1.2 CNS cancer 0.5 (neuro; met) SK-N-AS Lung
ca. NCI-N417 0.1 CNS cancer (astro) 0.0 SF-539 Lung ca. LX-1 1.3
CNS cancer (astro) 0.1 SNB-75 Lung ca. NCI-H146 0.0 CNS cancer
(glio) 0.0 SNB-19 Lung ca. SHP-77 0.1 CNS cancer (glio) SF- 0.1 295
Lung ca. A549 0.1 Brain (Amygdala) 0.1 Pool Lung ca. NCI-H526 0.0
Brain (cerebellum) 100.0 Lung ca. NCI-H23 0.0 Brain (fetal) 0.1
Lung ca. NCI-H460 0.0 Brain (Hippocampus) 0.3 Pool Lung ca. HOP-62
0.0 Cerebral Cortex Pool 0.3 Lung ca. NCI-H522 0.1 Brain
(Substantia 0.3 nigra) Pool Liver 1.0 Brain (Thalamus) Pool 0.5
Fetal Liver 0.0 Brain (whole) 1.7 Liver ca. HepG2 0.0 Spinal Cord
Pool 3.8 Kidney Pool 0.2 Adrenal Gland 2.6 Fetal Kidney 0.5
Pituitary gland Pool 1.6 Renal ca. 786-0 0.0 Salivary Gland 2.2
Renal ca. A498 0.1 Thyroid (female) 2.4 Renal ca. ACHN 0.1
Pancreatic ca. 0.1 CAPAN2 Renal ca. UO-31 0.0 Pancreas Pool 0.6
[0710] TABLE-US-00184 TABLE OF Panel 4.1D Rel. Exp.(%) Rel. Exp.(%)
Ag4386, Run Ag4386, Run Tissue Name 186506628 Tissue Name 186506628
Secondary Th1 act 0.0 HUVEC IL-1beta 0.0 Secondary Th2 act 0.0
HUVEC IFN gamma 0.0 Secondary Tr1 act 1.3 HUVEC TNF alpha + IFN 0.0
gamma Secondary Th1 rest 0.0 HUVEC TNF alpha + IL4 0.4 Secondary
Th2 rest 0.5 HUVEC IL-11 0.0 Secondary Tr1 rest 0.0 Lung
Microvascular EC 0.5 none Primary Th1 act 0.0 Lung Microvascular EC
0.0 TNF alpha + IL-1beta Primary Th2 act 0.8 Microvascular Dermal
0.0 EC none Primary Tr1 act 0.0 Microsvasular Dermal 0.0 EC TNF
alpha + IL-1beta Primary Th1 rest 0.8 Bronchial epithelium 1.0 TNF
alpha + IL1beta Primary Th2 rest 0.6 Small airway epithelium 0.0
none Primary Tr1 rest 0.0 Small airway epithelium 0.0 TNF alpha +
IL-1beta CD45RA CD4 1.0 Coronery artery SMC 0.5 lymphocyte act rest
CD45RO CD4 4.8 Coronery artery SMC 0.0 lymphocyte act TNF alpha +
IL-1beta CD8 lymphocyte act 2.0 Astrocytes rest 1.0 Secondary CD8
4.7 Astrocytes TNF alpha + IL- 0.0 lymphocyte rest 1beta Secondary
CD8 0.4 KU-812 (Basophil) rest 0.0 lymphocyte act CD4 lymphocyte
none 0.0 KU-812 (Basophil) 0.0 PMA/ionomycin 2ry Th1/Th2/Tr1_anti-
0.5 CCD1106 0.0 CD95 CH11 (Keratinocytes) none LAK cells rest 0.5
CCD1106 0.0 (Keratinocytes) TNF alpha + IL-1beta LAK cells IL-2 0.0
Liver cirrhosis 1.0 LAK cells IL-2 + IL-12 0.0 NCI-H292 none 1.9
LAK cells IL-2 + IFN 2.4 NCI-H292 IL-4 0.7 gamma LAK cells IL-2 +
IL-18 0.0 NCI-H292 IL-9 0.6 LAK cells 3.6 NCI-H292 IL-13 0.0
PMA/ionomycin NK Cells IL-2 rest 3.7 NCI-H292 IFN gamma 0.0 Two Way
MLR 3 day 1.2 HPAEC none 0.0 Two Way MLR 5 day 0.5 HPAEC TNF alpha
+ IL- 0.7 1beta Two Way MLR 7 day 0.0 Lung fibroblast none 0.0 PBMC
rest 0.0 Lung fibroblast TNF 0.0 alpha + IL-1beta PBMC PWM 14.9
Lung fibroblast IL-4 0.0 PBMC PHA-L 5.0 Lung fibroblast IL-9 0.0
Ramos (B cell) none 0.0 Lung fibroblast IL-13 0.0 Ramos (B cell)
0.5 Lung fibroblast IFN 0.0 ionomycin gamma B lymphocytes PWM 1.5
Dermal fibroblast 0.0 CCD1070 rest B lymphocytes CD40L 0.4 Dermal
fibroblast 0.0 and IL-4 CCD1070 TNF alpha EOL-1 dbcAMP 0.0 Dermal
fibroblast 0.5 CCD1070 IL-1beta EOL-1 dbcAMP 0.0 Dermal fibroblast
IFN 1.0 PMA/ionomycin gamma Dendritic cells none 0.0 Dermal
fibroblast IL-4 0.3 Dendritic cells LPS 0.0 Dermal Fibroblasts rest
1.3 Dendritic cells anti- 0.0 Neutrophils TNFa + LPS 0.0 CD40
Monocytes rest 0.0 Neutrophils rest 0.0 Monocytes LPS 0.0 Colon 2.4
Macrophages rest 0.0 Lung 5.8 Macrophages LPS 0.0 Thymus 15.2 HUVEC
none 0.0 Kidney 100.0 HUVEC starved 0.0
[0711] CNS_neurodegeneration_v1.0 Summary: Ag4386 This panel
confirms the expression of the NOV16A gene at low levels in the
brains with highest expression in hippocampus of an Alzheimer
patient (CT=34.6). Therefore, therapeutic modulation of this gene
may be beneficial in the treatment of Alzheimer's disease.
[0712] General_screening_panel_v1.4 Summary: Ag4386 Highest
expression of the NOV16A gene is detected in brain (cerebellum)
(CT=27.4). In addition, moderate expression of this gene is also
detected thalamus, whole brain and spinal cord. Therefore,
therapeutic modulation of this gene product may be beneficial in
the treatment of neurological disorders such as Alzheimer's
disease, Parkinson's disease, epilepsy, multiple sclerosis,
schizophrenia and depression.
[0713] The NOV16A gene encodes a homolog of neuronal leucine rich
repeat protein (NLRR). In zebra fish the NLRR functions as a
neuronal-specific adhesion molecule or soluble ligand binding
receptor, primarily during restoration of the nervous system after
injury (Bormann et al., 1999, Mol Cell Neurosci 13 (3):167-79,
PMID: 10328879). Thus, NLRR encoded by this gene may also play
similar role in restoration of nervous system after injury.
[0714] Among tissues with metabolic or endocrine function, this
gene is expressed at low to moderate levels in pancreas, adrenal
gland, thyroid, pituitary gland, skeletal muscle, and liver.
Therefore, therapeutic modulation of the activity of this gene may
prove useful in the treatment of endocrine/metabolically related
diseases, such as obesity and diabetes.
[0715] Interestingly, this gene is expressed at much higher levels
in adult (CT=29.5) when compared to fetal skeletal muscle
(CT=34.3). This observation suggests that expression of this gene
can be used to distinguish fetal from adult skeletal muscle.
[0716] General_screening_panel_v1.6 Summary: Ag4386 Highest
expression of this gene is seen in the cerebellum (CT=26.7). This
is in agreement with expression seen in Panel 1.4. Overall,
expression in this panel is in agreement with expression in Panel
1.5. Please see that panel for further description and utility of
this gene in metabolic and CNS disorders.
[0717] Panel 4.1D Summary: Ag4386 Highest expression of the NOV16A
gene is detected in kidney (CT=30.7). Thus, expression of this gene
may be used to distinguish kidney sample from other samples in this
panel. In addition, low expression of this gene is also seen in
lung, thymus and PWM treated PBMC cells. Therefore, therapeutic
modulation of this gene product may be useful in the treatment of
inflammatory and autoimmune diseases affecting kidney and lung such
as lupus, glomerulonephritis, asthma, allergy, and COPD.
[0718] P. NOV17A: Immunoglobulin Domains Containing Protein
[0719] Expression of gene NOV17A was assessed using the
primer-probe set Ag4389, described in Table PA. Results of the
RTQ-PCR runs are shown in Tables PB, PC and PD. TABLE-US-00185
TABLE PA Probe Name Ag4389 Start SEQ ID Primers Sequences Length
Positions No Forward 5'-agagcctggaaattaccaatgt-3' 22 250 196 Probe
TET-5'-agacccgaggatcctccctcagtgat-3'- 26 273 197 TAMRA Reverse
5'-cagtcaggtgaaaattccacat-3' 22 306 198
[0720] TABLE-US-00186 TABLE PB General_screening_panel_v1.4 Rel.
Exp.(%) Rel. Exp.(%) Ag4389, Ag4389, Run Run Tissue Name 222641235
Tissue Name 222641235 Adipose 6.3 Renal ca. TK-10 0.0 Melanoma* 0.0
Bladder 4.0 Hs688(A).T Melanoma* 0.0 Gastric ca. (liver met.) 0.0
Hs688(B).T NCI-N87 Melanoma* M14 0.0 Gastric ca. KATO III 0.0
Melanoma* 0.0 Colon ca. SW-948 0.0 LOXIMVI Melanoma* SK- 0.5 Colon
ca. SW480 0.0 MEL-5 Squamous cell 0.2 Colon ca.* (SW480 0.0
carcinoma SCC-4 met) SW620 Testis Pool 0.9 Colon ca. HT29 0.0
Prostate ca.* (bone 0.0 Colon ca. HCT-116 0.0 met) PC-3 Prostate
Pool 0.7 Colon ca. CaCo-2 0.0 Placenta 1.0 Colon cancer tissue 1.4
Uterus Pool 0.6 Colon ca. SW1116 0.0 Ovarian ca. 0.0 Colon ca.
Colo-205 0.0 OVCAR-3 Ovarian ca. SK- 0.0 Colon ca. SW-48 0.0 OV-3
Ovarian ca. 0.0 Colon Pool 0.5 OVCAR-4 Ovarian ca. 1.7 Small
Intestine Pool 1.0 OVCAR-5 Ovarian ca. 0.0 Stomach Pool 1.5 IGROV-1
Ovarian ca. 0.0 Bone Marrow Pool 0.7 OVCAR-8 Ovary 0.0 Fetal Heart
0.2 Breast ca. MCF-7 0.0 Heart Pool 0.2 Breast ca. MDA- 0.0 Lymph
Node Pool 1.2 MB-231 Breast ca. BT 549 0.0 Fetal Skeletal Muscle
0.0 Breast ca. T47D 2.0 Skeletal Muscle Pool 0.3 Breast ca. MDA-N
0.0 Spleen Pool 100.0 Breast Pool 0.4 Thymus Pool 14.9 Trachea 6.8
CNS cancer 0.0 (glio/astro) U87-MG Lung 0.0 CNS cancer 0.2
(glio/astro) U-118-MG Fetal Lung 8.5 CNS cancer 0.4 (neuro; met)
SK-N-AS Lung ca. NCI-N417 0.0 CNS cancer (astro) 0.0 SF-539 Lung
ca. LX-1 0.0 CNS cancer (astro) 0.0 SNB-75 Lung ca. NCI-H146 0.0
CNS cancer (glio) 0.0 SNB-19 Lung ca. SHP-77 0.0 CNS cancer (glio)
SF- 0.0 295 Lung ca. A549 0.0 Brain (Amygdala) 0.0 Pool Lung ca.
NCI-H526 0.0 Brain (cerebellum) 0.0 Lung ca. NCI-H23 0.0 Brain
(fetal) 0.7 Lung ca. NCI-H460 0.0 Brain (Hippocampus) 0.0 Pool Lung
ca. HOP-62 0.0 Cerebral Cortex Pool 0.2 Lung ca. NCI-H522 0.0 Brain
(Substantia 0.0 nigra) Pool Liver 0.7 Brain (Thalamus) Pool 0.5
Fetal Liver 2.0 Brain (whole) 0.5 Liver ca. HepG2 0.0 Spinal Cord
Pool 0.0 Kidney Pool 1.4 Adrenal Gland 0.6 Fetal Kidney 0.0
Pituitary gland Pool 0.0 Renal ca. 786-0 0.0 Salivary Gland 1.5
Renal ca. A498 0.0 Thyroid (female) 0.2 Renal ca. ACHN 0.0
Pancreatic ca. 0.0 CAPAN2 Renal ca. UO-31 0.0 Pancreas Pool 0.5
[0721] TABLE-US-00187 TABLE PC Panel 4.1D Rel. Exp.(%) Rel. Exp.(%)
Ag4389, Run Ag4389, Run Tissue Name 186502087 Tissue Name 186502087
Secondary Th1 act 0.0 HUVEC IL-1beta 0.0 Secondary Th2 act 0.1
HUVEC IFN gamma 0.0 Secondary Tr1 act 0.1 HUVEC TNF alpha + IFN 0.0
gamma Secondary Th1 rest 0.7 HUVEC TNF alpha + IL4 0.0 Secondary
Th2 rest 5.5 HUVEC IL-11 0.5 Secondary Tr1 rest 0.0 Lung
Microvascular EC 0.0 none Primary Th1 act 1.0 Lung Microvascular EC
0.0 TNF alpha + IL-1beta Primary Th2 act 4.5 Microvascular Dermal
0.1 EC none Primary Tr1 act 0.5 Microsvasular Dermal 0.1 EC TNF
alpha + IL-1beta Primary Th1 rest 0.3 Bronchial epithelium 0.0 TNF
alpha + IL1beta Primary Th2 rest 1.5 Small airway epithelium 0.0
none Primary Tr1 rest 0.0 Small airway epithelium 0.0 TNF alpha +
IL-1beta CD45RA CD4 3.8 Coronery artery SMC 0.0 lymphocyte act rest
CD45RO CD4 7.0 Coronery artery SMC 0.0 lymphocyte act TNF alpha +
IL-1beta CD8 lymphocyte act 14.4 Astrocytes rest 0.0 Secondary CD8
2.3 Astrocytes TNF alpha + IL- 0.0 lymphocyte rest 1beta Secondary
CD8 5.9 KU-812 (Basophil) rest 0.0 lymphocyte act CD4 lymphocyte
none 6.9 KU-812 (Basophil) 0.0 PMA/ionomycin 2ry Th1/Th2/Tr1_anti-
1.4 CCD1106 0.0 CD95 CH11 (Keratinocytes) none LAK cells rest 15.1
CCD1106 0.0 (Keratinocytes) TNF alpha + IL-1beta LAK cells IL-2
26.8 Liver cirrhosis 1.0 LAK cells IL-2 + IL-12 12.2 NCI-H292 none
0.0 LAK cells IL-2 + IFN 16.0 NCI-H292 IL-4 0.0 gamma LAK cells
IL-2 + IL-18 15.9 NCI-H292 IL-9 0.0 LAK cells 26.8 NCI-H292 IL-13
0.0 PMA/ionomycin NK Cells IL-2 rest 59.5 NCI-H292 IFN gamma 0.0
Two Way MLR 3 day 31.2 HPAEC none 0.1 Two Way MLR 5 day 8.4 HPAEC
TNF alpha + IL- 0.0 1beta Two Way MLR 7 day 5.6 Lung fibroblast
none 0.0 PBMC rest 17.1 Lung fibroblast TNF 0.0 alpha + IL-1beta
PBMC PWM 5.5 Lung fibroblast IL-4 0.0 PBMC PHA-L 2.5 Lung
fibroblast IL-9 0.0 Ramos (B cell) none 1.8 Lung fibroblast IL-13
0.0 Ramos (B cell) 4.0 Lung fibroblast IFN 0.0 ionomycin gamma B
lymphocytes PWM 8.5 Dermal fibroblast 0.6 CCD1070 rest B
lymphocytes CD40L 100.0 Dermal fibroblast 0.7 and IL-4 CCD1070 TNF
alpha EOL-1 dbcAMP 0.0 Dermal fibroblast 0.0 CCD1070 IL-1beta EOL-1
dbcAMP 0.1 Dermal fibroblast IFN 0.5 PMA/ionomycin gamma Dendritic
cells none 7.3 Dermal fibroblast IL-4 0.0 Dendritic cells LPS 1.0
Dermal Fibroblasts rest 0.0 Dendritic cells anti- 0.2 Neutrophils
TNFa + LPS 1.4 CD40 Monocytes rest 2.8 Neutrophils rest 2.0
Monocytes LPS 3.7 Colon 8.0 Macrophages rest 19.1 Lung 1.4
Macrophages LPS 0.3 Thymus 7.3 HUVEC none 0.0 Kidney 25.9 HUVEC
starved 0.0
[0722] TABLE-US-00188 TABLE PD Panel CNS_1.1 Rel. Exp.(%) Rel.
Exp.(%) Ag4389, Ag4389, Run Run Tissue Name 190028469 Tissue Name
190028469 Cing Gyr 0.0 BA17 PSP2 0.0 Depression2 Cing Gyr 0.0 BA17
PSP 0.0 Depression Cing Gyr PSP2 0.0 BA17 0.0 Huntington's2 Cing
Gyr PSP 0.0 BA17 1.2 Huntington's Cing Gyr 0.0 BA17 0.0
Huntington's2 Parkinson's2 Cing Gyr 0.0 BA17 0.0 Huntington's
Parkinson's Cing Gyr 0.0 BA17 4.2 Parkinson's2 Alzheimer's2 Cing
Gyr 0.0 BA17 Control2 0.0 Parkinson's Cing Gyr 0.0 BA17 Control 0.0
Alzheimer's2 Cing Gyr 0.0 BA9 0.0 Alzheimer's Depression2 Cing Gyr
Control2 0.0 BA9 Depression 0.0 Cing Gyr Control 0.0 BA9 PSP2 0.0
Temp Pole 0.0 BA9 PSP 0.0 Depression2 Temp Pole PSP2 0.0 BA9 6.0
Huntington's2 Temp Pole PSP 0.0 BA9 0.0 Huntington's Temp Pole 0.0
BA9 0.0 Huntington's Parkinson's2 Temp Pole 0.0 BA9 Parkinson's 0.0
Parkinson's2 Temp Pole 0.0 BA9 0.0 Parkinson's Alzheimer's2 Temp
Pole 0.0 BA9 0.0 Alzheimer's2 Alzheimer's Temp Pole 0.0 BA9
Control2 5.4 Alzheimer's Temp Pole Control2 0.0 BA9 Control 0.0
Temp Pole Control 0.0 BA7 Depression 0.0 Glob Palladus 0.0 BA7 PSP2
0.0 Depression Glob Palladus PSP2 0.0 BA7 PSP 0.0 Glob Palladus PSP
0.0 BA7 0.0 Huntington's2 Glob Palladus 0.0 BA7 0.0 Parkinson's2
Huntington's Glob Palladus 0.0 BA7 0.0 Parkinson's Parkinson's2
Glob Palladus 0.0 BA7 Parkinson's 100.0 Alzheimer's2 Glob Palladus
0.0 BA7 0.0 Alzheimer's Alzheimer's2 Glob Palladus 0.0 BA7 Control2
0.0 Control2 Glob Palladus 0.0 BA7 Control 0.0 Control Sub Nigra
0.0 BA4 0.0 Depression2 Depression2 Sub Nigra 0.0 BA4 Depression
0.0 Depression Sub Nigra PSP2 0.0 BA4 PSP2 0.0 Sub Nigra 0.0 BA4
PSP 0.0 Huntington's2 Sub Nigra 0.0 BA4 0.0 Huntington's
Huntington's2 Sub Nigra 0.0 BA4 0.0 Parkinson's2 Huntington's Sub
Nigra 0.0 BA4 0.0 Alzheimer's2 Parkinson's2 Sub Nigra Control2 0.0
BA4 Parkinson's 0.0 Sub Nigra Control 0.0 BA4 0.0 Alzheimer's2 BA17
Depression2 0.0 BA4 Control2 0.0 BA17 Depression 0.0 BA4 Control
0.0
[0723] CNS_neurodegeneration_v1.0 Summary: Ag4389 Expression of the
NOV17A gene is low/undetectable (CTs>35) across all of the
samples on this panel (data not shown).
[0724] General_screening_panel_v1.4 Summary: Ag4389 Highest
expression of the NOV17A gene is detected in spleen (CT=29).
Moderate expression of this gene is also detected in thymus. The
NOV17A gene encodes a protein similar to the immunoglobulin
receptor translocation associated (IRTA) protein. IRTA proteins are
immunoreceptors implicated in B cell development and
lymphomagenesis (Hatzivassiliou et al., 2001, Immunity 14
(3):277-89, PMID: 11290337). Therefore, therapeutic modulation of
IRTA-like protein encoded by this gene may be beneficial in the
treatment of diseases associated with B cells including B-cell
non-Hodgkin lymphoma and multiple myeloma.
[0725] In addition, low expression of this gene is also seen in
adipose, and fetal liver. Therefore, therapeutic modulation of the
activity of this gene may prove useful in the treatment of
endocrine/metabolically related diseases, such as obesity and
diabetes.
[0726] Significant expression of this gene is also detected in
fetal lung (CT=32.6). Interestingly, this gene is expressed at much
higher levels in fetal when compared to adult lung (CT=40). This
observation suggests that expression of this gene can be used to
distinguish fetal from adult lung. In addition, the relative
overexpression of this gene in fetal lung suggests that the protein
product may enhance lung growth or development in the fetus and
thus may also act in a regenerative capacity in the adult.
Therefore, therapeutic modulation of the protein encoded by this
gene could be useful in treatment of lung related diseases.
[0727] Panel 4.1D Summary: Ag4389 Highest expression of the NOV17A
gene is detected in CD40L and IL-4 treated B lymphocytes (CT=28.5).
In addition, significant expression of this gene is also seen in
monocytes, resting macrophages, PWM treated B lymphocytes, Ramos B
cells, LAK cells, Two Way MLR cells, IL2 treated NK cells, PWM/PHA
treated and resting PBMC cells, CD4 and CD8 lymphocytes, primary
and secondary Th2 cells and in normal tissues represented by colon,
lung, thymus and kidney. Therefore, therapeutic modulation of this
gene product may be beneficial in the treatment of autoimmune and
inflammatory diseases in which B and Th2 cells play a part in the
initiation or progression of the disease process, such as systemic
lupus erythematosus, Crohn's disease, ulcerative colitis, multiple
sclerosis, chronic obstructive pulmonary disease, asthma,
emphysema, rheumatoid arthritis, or psoriasis.
[0728] Panel CNS.sub.--1 Summary: Ag4389 Expression of the NOV17A
gene is low/undetectable (CTs>35) across all of the samples on
this panel (data not shown).
[0729] Panel CNS.sub.--1.1 Summary: Ag4389 This panel confirms the
expression of the NOV17A gene at very low levels in the brain of an
independent group of individuals, with highest expression in a
sample from Parkinson's patient. Therefore, therapeutic modulation
of this gene product may be beneficial in the treatment of
Parkinson's disease.
[0730] Q. NOV18A, NOV18B and NOV18C: Small Inducible Cytokine B14
Precursor (Chemokine BRAK)
[0731] Expression of gene NOV18A and variants NOV18B and NOV18C was
assessed using the primer-probe set Ag953, described in Table QA.
Results of the RTQ-PCR runs are shown in Tables QB, QC, QD and QE.
Please note that NOV18A and NOV18C represent full-length physical
clones. TABLE-US-00189 TABLE QA Probe Name Ag953 Start SEQ ID
Primers Sequences Length Position No Forward
5'-ccaagagcgtgtccaggta-3' 19 110 199 Probe
TET-5'-agagcaccaagcgcttcatcaagtg-3'- 25 164 200 TAMRA Reverse
5'-ctcgttccaggcgttgtac-3' 19 189 201
[0732] TABLE-US-00190 TABLE QB A1_comprehensive panel_v1.0 Rel.
Exp.(%) Rel. Exp.(%) Ag953, Run Ag953, Run Tissue Name 247834379
Tissue Name 247834379 110967 COPD-F 0.0 112427 Match Control 0.2
Psoriasis-F 110980 COPD-F 0.2 112418 Psoriasis-M 0.1 110968 COPD-M
0.0 112723 Match Control 0.0 Psoriasis-M 110977 COPD-M 0.2 112419
Psoriasis-M 0.1 110989 0.1 112424 Match Control 0.2 Emphysema-F
Psoriasis-M 110992 42.3 112420 Psoriasis-M 1.1 Emphysema-F 110993
0.1 112425 Match Control 0.1 Emphysema-F Psoriasis-M 110994 0.1
104689 (MF) OA 5.0 Emphysema-F Bone-Backus 110995 100.0 104690 (MF)
Adj 4.4 Emphysema-F "Normal" Bone- Backus 110996 22.7 104691 (MF)
OA 12.1 Emphysema-F Synovium-Backus 110997 Asthma-M 6.8 104692 (BA)
OA 2.5 Cartilage-Backus 111001 Asthma-F 0.5 104694 (BA) OA 3.9
Bone-Backus 111002 Asthma-F 0.4 104695 (BA) Adj 1.0 "Normal" Bone-
Backus 111003 Atopic 0.2 104696 (BA) OA 31.6 Asthma-F
Synovium-Backus 111004 Atopic 0.3 104700 (SS) OA 2.6 Asthma-F
Bone-Backus 111005 Atopic 0.2 104701 (SS) Adj 4.0 Asthma-F "Normal"
Bone- Backus 111006 Atopic 0.0 104702 (SS) OA 14.2 Asthma-F
Synovium-Backus 111417 Allergy-M 0.1 117093 OA Cartilage 0.6 Rep7
112347 Allergy-M 0.1 112672 OA Bone5 0.1 112349 Normal 0.2 112673
OA 0.0 Lung-F Synovium5 112357 Normal 0.1 112674 OA Synovial 0.0
Lung-F Fluid cells5 112354 Normal 0.7 117100 OA Cartilage 0.1
Lung-M Rep14 112374 Crohns-F 1.5 112756 OA Bone9 0.0 112389 Match
15.3 112757 OA 3.1 Control Crohns-F Synovium9 112375 Crohns-F 1.2
112758 OA Synovial 1.3 Fluid Cells9 112732 Match 2.6 117125 RA
Cartilage 0.1 Control Crohns-F Rep2 112725 Crohns-M 0.1 113492
Bone2 RA 0.6 112387 Match 0.9 113493 Synovium2 0.4 Control Crohns-M
RA 112378 Crohns-M 0.2 113494 Syn Fluid 0.6 Cells RA 112390 Match
0.2 113499 Cartilage4 RA 0.2 Control Crohns-M 112726 Crohns-M 2.5
113500 Bone4 RA 0.2 112731 Match 3.0 113501 Synovium4 0.1 Control
Crohns-M RA 112380 Ulcer Col-F 0.1 113502 Syn Fluid 0.1 Cells4 RA
112734 Match 7.1 113495 Cartilage3 RA 0.1 Control Ulcer Col-F
112384 Ulcer Col-F 48.3 113496 Bone3 RA 0.1 112737 Match 2.2 113497
Synovium3 0.0 Control Ulcer Col-F RA 112386 Ulcer Col-F 1.1 113498
Syn Fluid 0.1 Cells3 RA 112738 Match 1.3 117106 Normal 0.0 Control
Ulcer Col-F Cartilage Rep20 112381 Ulcer Col- 1.0 113663 Bone3
Normal 0.1 M 112735 Match 0.8 113664 Synovium3 0.0 Control Ulcer
Col- Normal M 112382 Ulcer Col- 11.5 113665 Syn Fluid 0.0 M Cells3
Normal 112394 Match 1.0 117107 Normal 0.2 Control Ulcer Col-
Cartilage Rep22 M 112383 Ulcer Col- 35.4 113667 Bone4 Normal 0.5 M
112736 Match 8.4 113668 Synovium4 0.7 Control Ulcer Col- Normal M
112423 Psoriasis-F 0.3 113669 Syn Fluid 0.7 Cells4 Normal
[0733] TABLE-US-00191 TABLE QC Panel 2D Rel. Exp.(%) Rel. Exp.(%)
Ag953, Run Ag953, Run Tissue Name 170849612 Tissue Name 170849612
Normal Colon 36.6 Kidney Margin 43.8 8120608 CC Well to Mod Diff
0.4 Kidney Cancer 0.1 (ODO3866) 8120613 CC Margin 8.3 Kidney Margin
43.8 (ODO3866) 8120614 CC Gr.2 rectosigmoid 1.3 Kidney Cancer 3.1
(ODO3868) 9010320 CC Margin 0.3 Kidney Margin 81.2 (ODO3868)
9010321 CC Mod Diff 4.4 Normal Uterus 0.1 (ODO3920) CC Margin 1.6
Uterus Cancer 2.2 (ODO3920) 064011 CC Gr.2 ascend colon 28.3 Normal
Thyroid 3.7 (ODO3921) CC Margin 4.3 Thyroid Cancer 0.1 (ODO3921)
064010 CC from Partial 2.3 Thyroid Cancer 1.1 Hepatectomy A302152
(ODO4309) Mets Liver Margin 3.1 Thyroid Margin 1.6 (ODO4309)
A302153 Colon mets to lung 0.2 Normal Breast 17.2 (OD04451-01) Lung
Margin 0.0 Breast Cancer 43.8 (OD04451-02) (OD04566) Normal
Prostate 2.8 Breast Cancer 9.0 6546-1 (OD04590-01) Prostate Cancer
8.7 Breast Cancer Mets 14.9 (OD04410) (OD04590-03) Prostate Margin
0.5 Breast Cancer 4.1 (OD04410) Metastasis (OD04655-05) Prostate
Cancer 3.0 Breast Cancer 28.7 (OD04720-01) 064006 Prostate Margin
1.8 Breast Cancer 1024 14.4 (OD04720-02) Normal Lung 061010 5.2
Breast Cancer 16.5 9100266 Lung Met to Muscle 0.1 Breast Margin
20.7 (ODO4286) 9100265 Muscle Margin 22.8 Breast Cancer 10.5
(ODO4286) A209073 Lung Malignant 3.9 Breast Margin 10.4 Cancer
(OD03126) A209073 Lung Margin 0.5 Normal Liver 4.6 (OD03126) Lung
Cancer 27.4 Liver Cancer 0.1 (OD04404) 064003 Lung Margin 3.0 Liver
Cancer 1025 3.5 (OD04404) Lung Cancer 27.2 Liver Cancer 1026 0.7
(OD04565) Lung Margin 0.0 Liver Cancer 4.5 (OD04565) 6004-T Lung
Cancer 7.5 Liver Tissue 0.3 (OD04237-01) 6004-N Lung Margin 0.2
Liver Cancer 0.5 (OD04237-02) 6005-T Ocular Mel Met to 0.0 Liver
Tissue 1.2 Liver (ODO4310) 6005-N Liver Margin 2.5 Normal Bladder
2.8 (ODO4310) Melanoma Mets to 0.2 Bladder Cancer 1.6 Lung
(OD04321) 1023 Lung Margin 0.5 Bladder Cancer 45.4 (OD04321)
A302173 Normal Kidney 63.3 Bladder Cancer 0.1 (OD04718-01) Kidney
Ca, Nuclear 23.2 Bladder Normal 12.3 grade 2 (OD04338) Adjacent
(OD04718-03) Kidney Margin 22.2 Normal Ovary 0.2 (OD04338) Kidney
Ca Nuclear 20.4 Ovarian Cancer 21.5 grade 1/2 (OD04339) 064008
Kidney Margin 100.0 Ovarian Cancer 0.0 (OD04339) (OD04768-07)
Kidney Ca, Clear cell 39.8 Ovary Margin 2.3 type (OD04340)
(OD04768-08) Kidney Margin 26.6 Normal Stomach 8.9 (OD04340) Kidney
Ca, Nuclear 1.0 Gastric Cancer 3.5 grade 3 (OD04348) 9060358 Kidney
Margin 12.1 Stomach Margin 10.6 (OD04348) 9060359 Kidney Cancer
32.1 Gastric Cancer 3.1 (OD04622-01) 9060395 Kidney Margin 6.3
Stomach Margin 11.4 (OD04622-03) 9060394 Kidney Cancer 9.0 Gastric
Cancer 12.9 (OD04450-01) 9060397 Kidney Margin 31.6 Stomach Margin
4.0 (OD04450-03) 9060396 Kidney Cancer 1.2 Gastric Cancer 6.3
8120607 064005
[0734] TABLE-US-00192 TABLE QD Panel 3D Rel. Exp.(%) Rel. Exp.(%)
Ag953, Ag953, Tissue Name Run 168032587 Tissue Name Run 168032587
Daoy-Medulloblastoma 0.7 Ca Ski-Cervical epidermoid 0.0 carcinoma
(metastasis) TE671- 0.0 ES-2-Ovarian clear cell 0.0 Medulloblastoma
carcinoma D283 Med- 0.0 Ramos-Stimulated with 0.0 Medulloblastoma
PMA/ionomycin 6 h PFSK-1-Primitive 0.0 Ramos-Stimulated with 0.0
Neuroectodermal PMA/ionomycin 14 h XF-498-CNS 0.5 MEG-01-Chronic
1.6 myelogenous leukemia (megokaryoblast) SNB-78-Glioma 0.0
Raji-Burkitt's lymphoma 0.0 SF-268-Glioblastoma 0.0 Daudi-Burkitt's
lymphoma 0.0 T98G-Glioblastoma 4.0 U266-B-cell plasmacytoma 0.0
SK-N-SH- 0.0 CA46-Burkitt's lymphoma 0.1 Neuroblastoma (metastasis)
SF-295-Glioblastoma 0.0 RL-non-Hodgkin's B-cell 0.0 lymphoma
Cerebellum 2.6 JM1-pre-B-cell lymphoma 0.0 Cerebellum 2.4 Jurkat-T
cell leukemia 0.0 NCI-H292- 0.0 TF-1-Erythroleukemia 1.7
Mucoepidermoid lung carcinoma DMS-114-Small cell 0.0 HUT 78-T-cell
lymphoma 0.1 lung cancer DMS-79-Small cell 1.2 U937-Histiocytic
lymphoma 0.1 lung cancer NCI-H146-Small cell 9.7 KU-812-Myelogenous
1.9 lung cancer leukemia NCI-H526-Small cell 0.4 769-P-Clear cell
renal 0.3 lung cancer carcinoma NCI-N417-Small cell 0.5
Caki-2-Clear cell renal 0.0 lung cancer carcinoma NCI-H82-Small
cell 0.2 SW 839-Clear cell renal 0.1 lung cancer carcinoma
NCI-H157-Squamous 0.0 G401-Wilms' tumor 0.0 cell lung cancer
(metastasis) NCI-H1155-Large cell 0.0 Hs766T-Pancreatic 0.0 lung
cancer carcinoma (LN metastasis) NCI-H1299-Large cell 0.0
CAPAN-1-Pancreatic 0.0 lung cancer adenocarcinoma (liver
metastasis) NCI-H727-Lung 0.0 SU86.86-Pancreatic 0.1 carcinoid
carcinoma (liver metastasis) NCI-UMC-11-Lung 0.0 BxPC-3-Pancreatic
4.1 carcinoid adenocarcinoma LX-1-Small cell lung 0.0
HPAC-Pancreatic 100.0 cancer adenocarcinoma Colo-205-Colon cancer
0.0 MIA PaCa-2-Pancreatic 0.1 carcinoma KM12-Colon cancer 0.0
CFPAC-1-Pancreatic ductal 74.2 adenocarcinoma KM20L2-Colon cancer
0.0 PANC-1-Pancreatic 0.0 epithelioid ductal carcinoma
NCI-H716-Colon 0.0 T24-Bladder carcinma 0.0 cancer (transitional
cell) SW-48-Colon 11.2 5637-Bladder carcinoma 0.0 adenocarcinoma
SW1116-Colon 0.0 HT-1197-Bladder 0.0 adenocarcinoma carcinoma LS
174T-Colon 76.3 UM-UC-3-Bladder 0.0 adenocarcinoma carcinma
(transitional cell) SW-948-Colon 0.0 A204-Rhabdomyosarcoma 0.0
adenocarcinoma SW-480-Colon 0.0 HT-1080-Fibrosarcoma 0.0
adenocarcinoma NCI-SNU-5-Gastric 0.9 MG-63-Osteosarcoma 0.7
carcinoma KATO III-Gastric 0.0 SK-LMS-1- 0.0 carcinoma
Leiomyosarcoma (vulva) NCI-SNU-16-Gastric 0.0 SJRH30- 0.0 carcinoma
Rhabdomyosarcoma (met to bone marrow) NCI-SNU-1-Gastric 0.0
A431-Epidermoid 0.0 carcinoma carcinoma RF-1-Gastric 0.0
WM266-4-Melanoma 0.3 adenocarcinoma RF-48-Gastric 0.0 DU
145-Prostate carcinoma 0.0 adenocarcinoma (brain metastasis)
MKN-45-Gastric 0.0 MDA-MB-468-Breast 0.0 carcinoma adenocarcinoma
NCI-N87-Gastric 0.8 SCC-4-Squamous cell 0.0 carcinoma carcinoma of
tongue OVCAR-5-Ovarian 0.0 SCC-9-Squamous cell 0.0 carcinoma
carcinoma of tongue RL95-2-Uterine 0.0 SCC-15-Squamous cell 0.0
carcinoma carcinoma of tongue HelaS3-Cervical 0.0 CAL 27-Squamous
cell 0.4 adenocarcinoma carcinoma of tongue
[0735] TABLE-US-00193 TABLE QE Panel 4D Rel. Exp.(%) Rel. Exp.(%)
Ag953, Ag953, Tissue Name Run 168033522 Tissue Name Run 168033522
Secondary Th1 act 0.0 HUVEC IL-1beta 0.0 Secondary Th2 act 0.0
HUVEC IFN gamma 0.0 Secondary Tr1 act 0.0 HUVEC TNF alpha + IFN 0.0
gamma Secondary Th1 rest 0.0 HUVEC TNF alpha + IL4 0.0 Secondary
Th2 rest 0.0 HUVEC IL-11 0.0 Secondary Tr1 rest 0.0 Lung
Microvascular EC 0.0 none Primary Th1 act 0.0 Lung Microvascular EC
0.0 TNF alpha + IL-1beta Primary Th2 act 0.0 Microvascular Dermal
0.0 EC none Primary Tr1 act 0.0 Microsvasular Dermal 0.0 EC TNF
alpha + IL-1beta Primary Th1 rest 0.0 Bronchial epithelium 5.4 TNF
alpha + IL1beta Primary Th2 rest 0.0 Small airway epithelium 1.9
none Primary Tr1 rest 0.0 Small airway epithelium 10.2 TNF alpha +
IL-1beta CD45RA CD4 0.0 Coronery artery SMC rest 0.0 lymphocyte act
CD45RO CD4 0.0 Coronery artery SMC 0.0 lymphocyte act TNF alpha +
IL-1beta CD8 lymphocyte act 0.0 Astrocytes rest 1.7 Secondary CD8
0.0 Astrocytes TNF alpha + IL- 0.4 lymphocyte rest 1beta Secondary
CD8 0.0 KU-812 (Basophil) rest 0.4 lymphocyte act CD4 lymphocyte
none 0.0 KU-812 (Basophil) 0.4 PMA/ionomycin 2ry Th1/Th2/Tr1_anti-
0.0 CCD1106 0.1 CD95 CH11 (Keratinocytes) none LAK cells rest 0.0
CCD1106 0.3 (Keratinocytes) TNF alpha + IL-1beta LAK cells IL-2 0.0
Liver cirrhosis 0.8 LAK cells IL-2 + IL-12 0.0 Lupus kidney 5.1 LAK
cells IL-2 + IFN 0.0 NCI-H292 none 0.0 gamma LAK cells IL-2 + IL-18
0.0 NCI-H292 IL-4 0.0 LAK cells 0.0 NCI-H292 IL-9 0.0 PMA/ionomycin
NK Cells IL-2 rest 0.0 NCI-H292 IL-13 0.0 Two Way MLR 3 day 0.0
NCI-H292 IFN gamma 0.0 Two Way MLR 5 day 0.0 HPAEC none 0.0 Two Way
MLR 7 day 0.0 HPAEC TNF alpha + IL- 0.0 1beta PBMC rest 0.0 Lung
fibroblast none 0.0 PBMC PWM 0.0 Lung fibroblast TNF 0.0 alpha +
IL-1beta PBMC PHA-L 0.0 Lung fibroblast IL-4 0.1 Ramos (B cell)
none 0.0 Lung fibroblast IL-9 0.0 Ramos (B cell) 0.0 Lung
fibroblast IL-13 0.0 ionomycin B lymphocytes PWM 0.0 Lung
fibroblast IFN 0.0 gamma B lymphocytes CD40L 0.0 Dermal fibroblast
0.9 and IL-4 CCD1070 rest EOL-1 dbcAMP 0.0 Dermal fibroblast 0.6
CCD1070 TNF alpha EOL-1 dbcAMP 0.0 Dermal fibroblast 0.3
PMA/ionomycin CCD1070 IL-1beta Dendritic cells none 0.0 Dermal
fibroblast IFN 0.0 gamma Dendritic cells LPs 0.0 Dermal fibroblast
IL-4 0.1 Dendritic cells anti- 0.0 IBD Colitis 2 1.4 CD40 Monocytes
rest 0.0 IBD Crohn's 1.1 Monocytes LPS 0.0 Colon 21.0 Macrophages
rest 0.0 Lung 1.3 Macrophages LPS 0.0 Thymus 100.0 HUVEC none 0.0
Kidney 5.0 HUVEC starved 0.0
[0736] AI_comprehensive_panel_v1.0 Summary: Ag953 Highest
expression of the NOV18B gene is seen in emphysema (CT=23).
Moderate levels of expression are seen in many of the samples on
this panel suggesting a role for this protein product in the immune
system. Please see Panel 4D for disscussion of utility of this gene
in autoimmunity.
[0737] Panel 1.3D Summary: Ag953 Results from one experiment with
the CG56003-01 gene are not included. The amp plot indicates that
there were experimental difficulties with this run (data not
shown).
[0738] Panel 2D Summary: Ag953 Highest expression of the CG51213-02
gene is seen in normal kidney adjacent to a tumor (CT=24.8). In
addition, this gene appears to be overexpressed in normal kidney
when compared to expression in adjacent tumor. In contrast,
expression of this gene appears to be higher in lung and colon
cancer than in the adjacent tissue. High levels of expression are
also seen in bladder and ovarian cancers. This gene encodes a
protein with homology to cytokines which are molecular growth
factors involved in the regulation of cell proliferation. Thus,
this gene product may potentially be involved in the growth
regulation of cancer cells. Since blockade of the action of this
factor may interfere with cancer cell proliferation, therapeutic
targeting with a human monoclonal antibody may be beneficial
especially in those cancers where the gene is overexpressed in the
tumor compared to the normal adjacent tissue. Additionally,
application of the protein encoded by this gene may be useful as a
therapeutic for cancers where the gene is overexpressed in the
normal adjacent tissue compared to the tumor.
[0739] Panel 3D Summary: Ag953 Highest expression of the CG51213-02
gene is seen in a pancreatic cancer cell line (CT=28.1). Moderate
levels of expression are also seen in a colon cancer and a lung
cell line. Thus, expression of this gene could be used to
differentiate these samples from other samples on this panel.
[0740] Panel 4D Summary: Ag953 High expression of the CG51213-02
gene is seen the thymus (CT=25) and colon. Moderate levels of
expression are seen in kidney, lung, Crohn's, colitis, resting
dermal fibroblasts, lupus kidney, resting astrocytes, activated
bronchial epithelium, and treated and untreated small airway
epithelium. Low but significant levels of expression are seen in
activated dermal fibroblasts and astrocytes, and treated and
untreated basophils and keratinocytes. The high levels of
expression in the thymus suggest that expression of this could be
used to differentiate this sample from other samples and as a
marker of thymic tissue. Therapeutic modulation of the protein
encoded by this gene could potentially be utilized to modulate
immune function (T cell development) and be important for organ
transplant, AIDS treatment or post chemotherapy immune
reconstitution.
Example D
Identification of Single Nucleotide Polymorphisms in NOVX Nucleic
Acid Sequences
[0741] Variant sequences are also included in this application. A
variant sequence can include a single nucleotide polymorphism
(SNP). A SNP can, in some instances, be referred to as a "cSNP" to
denote that the nucleotide sequence containing the SNP originates
as a cDNA. A SNP can arise in several ways. For example, a SNP may
be due to a substitution of one nucleotide for another at the
polymorphic site. Such a substitution can be either a transition or
a transversion. A SNP can also arise from a deletion of a
nucleotide or an insertion of a nucleotide, relative to a reference
allele. In this case, the polymorphic site is a site at which one
allele bears a gap with respect to a particular nucleotide in
another allele. SNPs occurring within genes may result in an
alteration of the amino acid encoded by the gene at the position of
the SNP. Intragenic SNPs may also be silent, when a codon including
a SNP encodes the same amino acid as a result of the redundancy of
the genetic code. SNPs occurring outside the region of a gene, or
in an intron within a gene, do not result in changes in any amino
acid sequence of a protein but may result in altered regulation of
the expression pattern. Examples include alteration in temporal
expression, physiological response regulation, cell type expression
regulation, intensity of expression, and stability of transcribed
message.
[0742] SeqCalling assemblies produced by the exon linking process
were selected and extended using the following criteria. Genomic
clones having regions with 98% identity to all or part of the
initial or extended sequence were identified by BLASTN searches
using the relevant sequence to query human genomic databases. The
genomic clones that resulted were selected for further analysis
because this identity indicates that these clones contain the
genomic locus for these SeqCalling assemblies. These sequences were
analyzed for putative coding regions as well as for similarity to
the known DNA and protein sequences. Programs used for these
analyses include Grail, Genscan, BLAST, HMMER, FASTA, Hybrid and
other relevant programs.
[0743] Some additional genomic regions may have also been
identified because selected SeqCalling assemblies map to those
regions. Such SeqCalling sequences may have overlapped with regions
defined by homology or exon prediction. They may also be included
because the location of the fiagment was in the vicinity of genomic
regions identified by similarity or exon prediction that had been
included in the original predicted sequence. The sequence so
identified was manually assembled and then may have been extended
using one or more additional sequences taken from CuraGen
Corporation's human SeqCalling database. SeqCalling fragments
suitable for inclusion were identified by the CuraTools.TM. program
SeqExtend or by identifying SeqCalling fragments mapping to the
appropriate regions of the genomic clones analyzed.
[0744] The regions defined by the procedures described above were
then manually integrated and corrected for apparent inconsistencies
that may have arisen, for example, from miscalled bases in the
original fragments or from discrepancies between predicted exon
junctions, EST locations and regions of sequence similarity, to
derive the final sequence disclosed herein. When necessary, the
process to identify and analyze SeqCalling assemblies and genomic
clones was reiterated to derive the full length sequence (Alderbom
et al., Determination of Single Nucleotide Polymorphisms by
Real-time Pyrophosphate DNA Sequencing. Genome Research. 10 (8)
1249-1265, 2000).
[0745] Variants are reported individually but any combination of
all or a select subset of variants are also included as
contemplated NOVX embodiments of the invention.
NOV3a SNP Data:
[0746] NOV3a has one SNP variant, whose variant positions for its
nucleotide and amino acid sequences is numbered according to SEQ ID
NOs:25 and 26, respectively. The nucleotide sequence of the NOV3a
variant differs as shown in Table 20A. TABLE-US-00194 TABLE 20A
data for NOV3a Nucleotides Amino Acids Variant Position Initial
Modified Position Initial Modified 13379134 370 T C 115 Cys Arg
NOV5a SNP Data:
[0747] NOV5a has three SNP variants, whose variant positions for
its nucleotide and amino acid sequences is numbered according to
SEQ ID NOs:29 and 30, respectively. The nucleotide sequence of the
NOV5a variant differs as shown in Table 20B. TABLE-US-00195 TABLE
20B data for NOV5a Nucleotides Amino Acids Variant Position Initial
Modified Position Initial Modified 13379138 534 G A 177 Lys Lys
13379139 560 G T 186 Cys Phe 13379140 1124 C T 0
NOV10a SNP Data:
[0748] NOV10a has three SNP variants, whose variant positions for
its nucleotide and amino acid sequences is numbered according to
SEQ ID NOs:53 and 54, respectively. The nucleotide sequence of the
NOV10a variant differs as shown in Table 20C. TABLE-US-00196 TABLE
20C data for NOV10a Nucleotides Amino Acids Variant Position
Initial Modified Position Initial Modified 13379143 172 G C 57 Ala
Pro 13379142 197 A G 65 Asp Gly 13379141 398 G A 132 Ser Asn
NOV12a SNP Data:
[0749] NOV12a has seven SNP variants, whose variant positions for
its nucleotide and amino acid sequences is numbered according to
SEQ ID NOs:69 and 70, respectively. The nucleotide sequence of the
NOV12a variant differs as shown in Table 20D. TABLE-US-00197 TABLE
20D data for NOV12a Nucleotides Amino Acids Variant Position
Initial Modified Position Initial Modified 13379160 237 A G 79 Thr
Thr 13379161 446 C T 149 Thr Met 13376279 636 T G 212 Ile Met
13379162 710 G A 237 Gly Asp 13376278 893 C T 298 Thr Ile 13375449
1177 T C 393 Ser Pro 13379150 1194 T C 398 Ser Ser
NOV13a SNP Data:
[0750] NOV13a has one SNP variant, whose variant positions for its
nucleotide and amino acid sequences is numbered according to SEQ ID
NOs:85 and 86, respectively. The nucleotide sequence of the NOV13a
variant differs as shown in Table 20E. TABLE-US-00198 TABLE 20E
data for NOV13a Nucleotides Amino Acids Variant Position Initial
Modified Position Initial Modified 13379144 915 G A 232 Leu Leu
NOV14a SNP Data:
[0751] NOV14a has four SNP variants, whose variant positions for
its nucleotide and amino acid sequences is numbered according to
SEQ ID NOs:87 and 88, respectively. The nucleotide sequence of the
NOV14a variant differs as shown in Table 20F. TABLE-US-00199 TABLE
20F data for NOV14a Nucleotides Amino Acids Variant Position
Initial Modified Position Initial Modified 13379164 33 C T 8 Pro
Pro 13379165 117 T C 36 Ala Ala 13379167 575 T C 189 Leu Pro
13379168 686 T C 226 Leu Ser
NOV17a SNP Data:
[0752] NOV17a has four SNP variants, whose variant positions for
its nucleotide and amino acid sequences is numbered according to
SEQ ID NOs:93 and 94, respectively. The nucleotide sequence of the
NOV17a variant differs as shown in Table 20G. TABLE-US-00200 TABLE
20G data for NOV17a Nucleotides Amino Acids Variant Position
Initial Modified Position Initial Modified 13377348 521 T C 166 Tyr
His 13377349 1731 C A 569 Pro His
NOV18b SNP Data:
[0753] NOV18b has two SNP variants, whose variant positions for its
nucleotide and amino acid sequences is numbered according to SEQ ID
NOs:93 and 94, respectively. The nucleotide sequence of the NOV18b
variant differs as shown in Table 20H. TABLE-US-00201 TABLE 20H
data for NOV18b Nucleotides Amino Acids Variant Position Initial
Modified Position Initial Modified 13379152 114 G T 38 Lys Asn
13379151 222 C T 74 Tyr Tyr
NOV19a SNP Data:
[0754] NOV19a has one SNP variant, whose variant positions for its
nucleotide and amino acid sequences is numbered according to SEQ ID
NOs:107 and 108, respectively. The nucleotide sequence of the
NOV19a variant differs as shown in Table 201. TABLE-US-00202 TABLE
20I data for NOV19a Nucleotides Amino Acids Variant Position
Initial Modified Position Initial Modified 13379148 441 T C 147 His
His
OTHER EMBODIMENTS
[0755] Although particular embodiments have been disclosed herein
in detail, this has been done by way of example for purposes of
illustration only, and is not intended to be limiting with respect
to the scope of the appended claims, which follow. In particular,
it is contemplated by the inventors that various substitutions,
alterations, and modifications may be made to the invention without
departing from the spirit and scope of the invention as defined by
the claims. The choice of nucleic acid starting material, clone of
interest, or library type is believed to be a matter of routine for
a person of ordinary skill in the art with knowledge of the
embodiments described herein. Other aspects, advantages, and
modifications considered to be within the scope of the following
claims. The claims presented are representative of the inventions
disclosed herein. Other, unclaimed inventions are also
contemplated. Applicants reserve the right to pursue such
inventions in later claims.
Sequence CWU 1
1
201 1 1239 DNA Homo sapiens CDS (51)..(1167) 1 aaccagggcc
ttatccaggg ccacgcttac agaactccca cggacacacc atg att 56 Met Ile 1
agg acc ctg ctg ctg tcc act ttg gtg gcc ctc agt tgt ggg gtc tcc 104
Arg Thr Leu Leu Leu Ser Thr Leu Val Ala Leu Ser Cys Gly Val Ser 5
10 15 act tac gcg cct gat atg tct agg atg ctt gga ggt gaa gaa gcg
agg 152 Thr Tyr Ala Pro Asp Met Ser Arg Met Leu Gly Gly Glu Glu Ala
Arg 20 25 30 ccc aac agc tgg ccc tgg cag gtg agt ctg cag tac agc
tcc aat ggc 200 Pro Asn Ser Trp Pro Trp Gln Val Ser Leu Gln Tyr Ser
Ser Asn Gly 35 40 45 50 cag tgg tac cac acc tgc gga ggg tcc ctg ata
gcc aac agc tgg gtc 248 Gln Trp Tyr His Thr Cys Gly Gly Ser Leu Ile
Ala Asn Ser Trp Val 55 60 65 ctg acg gct gcc cac tgc atc agc tcc
tcc ggg atc tac cgc gtg atg 296 Leu Thr Ala Ala His Cys Ile Ser Ser
Ser Gly Ile Tyr Arg Val Met 70 75 80 ctg ggc cag cat aac ctc tac
gtt gca gag tcc ggc tcg ctg gcc gtc 344 Leu Gly Gln His Asn Leu Tyr
Val Ala Glu Ser Gly Ser Leu Ala Val 85 90 95 agt gtc tct aag att
gtg gtg cac aag gac tgg aac tcc gac cag gtc 392 Ser Val Ser Lys Ile
Val Val His Lys Asp Trp Asn Ser Asp Gln Val 100 105 110 tcc aaa ggg
aac gac att gcc ctg ctc aaa ctg gct aac ccc gtc tcc 440 Ser Lys Gly
Asn Asp Ile Ala Leu Leu Lys Leu Ala Asn Pro Val Ser 115 120 125 130
ctc acc gac aag atc cag ctg gcc tgc ctc cct cct gcc ggc acc att 488
Leu Thr Asp Lys Ile Gln Leu Ala Cys Leu Pro Pro Ala Gly Thr Ile 135
140 145 cta ccc aac aac tac ccc tgc tac gtc acg ggc tgg gga agg ctg
cag 536 Leu Pro Asn Asn Tyr Pro Cys Tyr Val Thr Gly Trp Gly Arg Leu
Gln 150 155 160 agt aac ggg gct ctc cct gat gac ctg aag cag ggc cag
ttg ctg gtt 584 Ser Asn Gly Ala Leu Pro Asp Asp Leu Lys Gln Gly Gln
Leu Leu Val 165 170 175 gtg gac tat gcc acc tgc tcc agc tct ggc tgg
tgg ggc agc acc gtg 632 Val Asp Tyr Ala Thr Cys Ser Ser Ser Gly Trp
Trp Gly Ser Thr Val 180 185 190 aag acg aat atg atc tgt gct ggg ggt
gat ggc gtg ata tgc acc tgc 680 Lys Thr Asn Met Ile Cys Ala Gly Gly
Asp Gly Val Ile Cys Thr Cys 195 200 205 210 aac gga gac tcc ggt ggg
ccg ctg aac tgt cag gca tct gac ggc cgg 728 Asn Gly Asp Ser Gly Gly
Pro Leu Asn Cys Gln Ala Ser Asp Gly Arg 215 220 225 tgg gag gtg cat
ggc atc ggc agc ctc acg tcg gtc ctt ggt tgc aac 776 Trp Glu Val His
Gly Ile Gly Ser Leu Thr Ser Val Leu Gly Cys Asn 230 235 240 tac tac
tac aag ccc tcc atc ttc acg cgg gtc tcc aac tac aac gac 824 Tyr Tyr
Tyr Lys Pro Ser Ile Phe Thr Arg Val Ser Asn Tyr Asn Asp 245 250 255
tgg atc aat tcg gta aga acc gga gca gcc ctg agc ccc aag gca ctg 872
Trp Ile Asn Ser Val Arg Thr Gly Ala Ala Leu Ser Pro Lys Ala Leu 260
265 270 acc tgc tca cct ggc ctc ggg agt gcc atg ccc acc tgg cga ctg
aga 920 Thr Cys Ser Pro Gly Leu Gly Ser Ala Met Pro Thr Trp Arg Leu
Arg 275 280 285 290 acc ccc tcc ttc ctc ttg aga gct aga tgg gaa ccc
ctt gga gga ggc 968 Thr Pro Ser Phe Leu Leu Arg Ala Arg Trp Glu Pro
Leu Gly Gly Gly 295 300 305 tgc aga cct tgg caa ctg ctg agt ccc cca
tgg gtc ccc aaa att tct 1016 Cys Arg Pro Trp Gln Leu Leu Ser Pro
Pro Trp Val Pro Lys Ile Ser 310 315 320 gtg tgg gta aag ctg agt gaa
aag gaa cat gag agt atg gcc ttg tcc 1064 Val Trp Val Lys Leu Ser
Glu Lys Glu His Glu Ser Met Ala Leu Ser 325 330 335 aaa gac gtt gga
cac tcc tca ggt acg tta aga gtg agt tcc aca gga 1112 Lys Asp Val
Gly His Ser Ser Gly Thr Leu Arg Val Ser Ser Thr Gly 340 345 350 atg
att tta ttt ttg tgt att tgt gtg tgg ccc aga ctc tac cat cca 1160
Met Ile Leu Phe Leu Cys Ile Cys Val Trp Pro Arg Leu Tyr His Pro 355
360 365 370 gtg cta taaatgggta tatgtctgca aaacccaaaa cctgatactt
tgagaccccc 1216 Val Leu atagcattaa ttattggaaa tta 1239 2 372 PRT
Homo sapiens 2 Met Ile Arg Thr Leu Leu Leu Ser Thr Leu Val Ala Leu
Ser Cys Gly 1 5 10 15 Val Ser Thr Tyr Ala Pro Asp Met Ser Arg Met
Leu Gly Gly Glu Glu 20 25 30 Ala Arg Pro Asn Ser Trp Pro Trp Gln
Val Ser Leu Gln Tyr Ser Ser 35 40 45 Asn Gly Gln Trp Tyr His Thr
Cys Gly Gly Ser Leu Ile Ala Asn Ser 50 55 60 Trp Val Leu Thr Ala
Ala His Cys Ile Ser Ser Ser Gly Ile Tyr Arg 65 70 75 80 Val Met Leu
Gly Gln His Asn Leu Tyr Val Ala Glu Ser Gly Ser Leu 85 90 95 Ala
Val Ser Val Ser Lys Ile Val Val His Lys Asp Trp Asn Ser Asp 100 105
110 Gln Val Ser Lys Gly Asn Asp Ile Ala Leu Leu Lys Leu Ala Asn Pro
115 120 125 Val Ser Leu Thr Asp Lys Ile Gln Leu Ala Cys Leu Pro Pro
Ala Gly 130 135 140 Thr Ile Leu Pro Asn Asn Tyr Pro Cys Tyr Val Thr
Gly Trp Gly Arg 145 150 155 160 Leu Gln Ser Asn Gly Ala Leu Pro Asp
Asp Leu Lys Gln Gly Gln Leu 165 170 175 Leu Val Val Asp Tyr Ala Thr
Cys Ser Ser Ser Gly Trp Trp Gly Ser 180 185 190 Thr Val Lys Thr Asn
Met Ile Cys Ala Gly Gly Asp Gly Val Ile Cys 195 200 205 Thr Cys Asn
Gly Asp Ser Gly Gly Pro Leu Asn Cys Gln Ala Ser Asp 210 215 220 Gly
Arg Trp Glu Val His Gly Ile Gly Ser Leu Thr Ser Val Leu Gly 225 230
235 240 Cys Asn Tyr Tyr Tyr Lys Pro Ser Ile Phe Thr Arg Val Ser Asn
Tyr 245 250 255 Asn Asp Trp Ile Asn Ser Val Arg Thr Gly Ala Ala Leu
Ser Pro Lys 260 265 270 Ala Leu Thr Cys Ser Pro Gly Leu Gly Ser Ala
Met Pro Thr Trp Arg 275 280 285 Leu Arg Thr Pro Ser Phe Leu Leu Arg
Ala Arg Trp Glu Pro Leu Gly 290 295 300 Gly Gly Cys Arg Pro Trp Gln
Leu Leu Ser Pro Pro Trp Val Pro Lys 305 310 315 320 Ile Ser Val Trp
Val Lys Leu Ser Glu Lys Glu His Glu Ser Met Ala 325 330 335 Leu Ser
Lys Asp Val Gly His Ser Ser Gly Thr Leu Arg Val Ser Ser 340 345 350
Thr Gly Met Ile Leu Phe Leu Cys Ile Cys Val Trp Pro Arg Leu Tyr 355
360 365 His Pro Val Leu 370 3 1188 DNA Homo sapiens CDS (1)..(868)
3 atg att agg acc ctg ctg ctg tcc act ttg gtg gct gga gcc ctc agt
48 Met Ile Arg Thr Leu Leu Leu Ser Thr Leu Val Ala Gly Ala Leu Ser
1 5 10 15 tgt ggg gtc tcc act tac gcg cct gat atg tct agg atg ctt
gga ggt 96 Cys Gly Val Ser Thr Tyr Ala Pro Asp Met Ser Arg Met Leu
Gly Gly 20 25 30 gaa gaa gcg agg ccc aac agc tgg ccc tgg cag gtg
agt ctg cag tac 144 Glu Glu Ala Arg Pro Asn Ser Trp Pro Trp Gln Val
Ser Leu Gln Tyr 35 40 45 agc tcc aat ggc cag tgg tac cac acc tgc
gga ggg tcc ctg ata gcc 192 Ser Ser Asn Gly Gln Trp Tyr His Thr Cys
Gly Gly Ser Leu Ile Ala 50 55 60 aac agc tgg gtc ctg acg gct gcc
cac tgc atc agc tcc tcc ggg atc 240 Asn Ser Trp Val Leu Thr Ala Ala
His Cys Ile Ser Ser Ser Gly Ile 65 70 75 80 tac cgc gtg atg ctg ggc
cag cat aac ctc tac gtt gca gag tcc ggc 288 Tyr Arg Val Met Leu Gly
Gln His Asn Leu Tyr Val Ala Glu Ser Gly 85 90 95 tcg ctg gcc gtc
agt gtc tct aag att gtg gtg cac aag gac tgg aac 336 Ser Leu Ala Val
Ser Val Ser Lys Ile Val Val His Lys Asp Trp Asn 100 105 110 tcc gac
cag gtc tcc aaa ggg aac gac att gcc ctg ctc aaa ctg gct 384 Ser Asp
Gln Val Ser Lys Gly Asn Asp Ile Ala Leu Leu Lys Leu Ala 115 120 125
aac ccc gtc tcc ctc acc gac aag atc cag ctg gcc tgc ctc cct cct 432
Asn Pro Val Ser Leu Thr Asp Lys Ile Gln Leu Ala Cys Leu Pro Pro 130
135 140 gcc ggc acc att cta ccc aac aac tac ccc tgc tac gtc acg ggc
tgg 480 Ala Gly Thr Ile Leu Pro Asn Asn Tyr Pro Cys Tyr Val Thr Gly
Trp 145 150 155 160 gga agg ctg cag acc aac ggg gct ctc cct gat gac
ctg aag cag ggc 528 Gly Arg Leu Gln Thr Asn Gly Ala Leu Pro Asp Asp
Leu Lys Gln Gly 165 170 175 cag ttg ctg gtt gtg gac tat gcc acc tgc
tcc agc tct ggc tgg tgg 576 Gln Leu Leu Val Val Asp Tyr Ala Thr Cys
Ser Ser Ser Gly Trp Trp 180 185 190 ggc agc acc gtg aag acg aat atg
atc tgt gct ggg ggt aat ggc gtg 624 Gly Ser Thr Val Lys Thr Asn Met
Ile Cys Ala Gly Gly Asn Gly Val 195 200 205 ata tgc acc tgc aac gga
gac tct ggc ggg cca ctg aac tgt cag gcg 672 Ile Cys Thr Cys Asn Gly
Asp Ser Gly Gly Pro Leu Asn Cys Gln Ala 210 215 220 tct gac ggc cgg
tgg cag gtg cac ggc atc gtc agc ttc ggg tct cgc 720 Ser Asp Gly Arg
Trp Gln Val His Gly Ile Val Ser Phe Gly Ser Arg 225 230 235 240 ctc
ggc tgc aac tac tac cac aag ccc tcc gtc ttc acg cgg gtc tcc 768 Leu
Gly Cys Asn Tyr Tyr His Lys Pro Ser Val Phe Thr Arg Val Ser 245 250
255 aat tac atc gac tgg atc aat tcg gta aga acc gga cca gcc ttg agc
816 Asn Tyr Ile Asp Trp Ile Asn Ser Val Arg Thr Gly Pro Ala Leu Ser
260 265 270 ccc aag gca cta ccc tgc tca cct ggc ctc ggg agt gcc atg
ccc acc 864 Pro Lys Ala Leu Pro Cys Ser Pro Gly Leu Gly Ser Ala Met
Pro Thr 275 280 285 tgg tgactgagaa tcccctcctt cctcttgaga gctagatggg
aaccccttgg 917 Trp aggaggctgc agacctgagt aactgctggg cctgccatgg
gtcccccaaa 967 tttctgtgtg gataaagctg agtgaaaagg aacatagagg
gtggccttgt 1017 ccaaagaggt tggacactcc tcaggcatat gaagagtgag
ttccgctggg 1067 cgccgtggct catgcctgta atcccagctc tttgggaggc
caaggcgggc 1117 agatcacgag gtcagaagtt caagaccagc ctgaccaacc
tggcaaaacc 1167 ccatgtctac taaaaaaatc c 1188 4 289 PRT Homo sapiens
4 Met Ile Arg Thr Leu Leu Leu Ser Thr Leu Val Ala Gly Ala Leu Ser 1
5 10 15 Cys Gly Val Ser Thr Tyr Ala Pro Asp Met Ser Arg Met Leu Gly
Gly 20 25 30 Glu Glu Ala Arg Pro Asn Ser Trp Pro Trp Gln Val Ser
Leu Gln Tyr 35 40 45 Ser Ser Asn Gly Gln Trp Tyr His Thr Cys Gly
Gly Ser Leu Ile Ala 50 55 60 Asn Ser Trp Val Leu Thr Ala Ala His
Cys Ile Ser Ser Ser Gly Ile 65 70 75 80 Tyr Arg Val Met Leu Gly Gln
His Asn Leu Tyr Val Ala Glu Ser Gly 85 90 95 Ser Leu Ala Val Ser
Val Ser Lys Ile Val Val His Lys Asp Trp Asn 100 105 110 Ser Asp Gln
Val Ser Lys Gly Asn Asp Ile Ala Leu Leu Lys Leu Ala 115 120 125 Asn
Pro Val Ser Leu Thr Asp Lys Ile Gln Leu Ala Cys Leu Pro Pro 130 135
140 Ala Gly Thr Ile Leu Pro Asn Asn Tyr Pro Cys Tyr Val Thr Gly Trp
145 150 155 160 Gly Arg Leu Gln Thr Asn Gly Ala Leu Pro Asp Asp Leu
Lys Gln Gly 165 170 175 Gln Leu Leu Val Val Asp Tyr Ala Thr Cys Ser
Ser Ser Gly Trp Trp 180 185 190 Gly Ser Thr Val Lys Thr Asn Met Ile
Cys Ala Gly Gly Asn Gly Val 195 200 205 Ile Cys Thr Cys Asn Gly Asp
Ser Gly Gly Pro Leu Asn Cys Gln Ala 210 215 220 Ser Asp Gly Arg Trp
Gln Val His Gly Ile Val Ser Phe Gly Ser Arg 225 230 235 240 Leu Gly
Cys Asn Tyr Tyr His Lys Pro Ser Val Phe Thr Arg Val Ser 245 250 255
Asn Tyr Ile Asp Trp Ile Asn Ser Val Arg Thr Gly Pro Ala Leu Ser 260
265 270 Pro Lys Ala Leu Pro Cys Ser Pro Gly Leu Gly Ser Ala Met Pro
Thr 275 280 285 Trp 5 889 DNA Homo sapiens CDS (1)..(799) 5 atg att
agg acc ctg ctg ctg tcc act ttg gtg gct gga gcc ctc agt 48 Met Ile
Arg Thr Leu Leu Leu Ser Thr Leu Val Ala Gly Ala Leu Ser 1 5 10 15
tgt ggg gtc tcc act tac gcg cct gat atg tct agg atg ctt gga ggt 96
Cys Gly Val Ser Thr Tyr Ala Pro Asp Met Ser Arg Met Leu Gly Gly 20
25 30 gaa gaa gcg agg ccc aac agc tgg ccc tgg cag gtg agt ctg cag
tac 144 Glu Glu Ala Arg Pro Asn Ser Trp Pro Trp Gln Val Ser Leu Gln
Tyr 35 40 45 agc tcc aat ggc cag tgg tac cac acc tgc gga ggg tcc
ctg ata gcc 192 Ser Ser Asn Gly Gln Trp Tyr His Thr Cys Gly Gly Ser
Leu Ile Ala 50 55 60 aac agc tgg gtc ctg acg gct gcc cac tgc atc
agc tcc tcc ggg atc 240 Asn Ser Trp Val Leu Thr Ala Ala His Cys Ile
Ser Ser Ser Gly Ile 65 70 75 80 tac cgc gtg atg ctg ggc cag cat aac
ctc tac gtt gca gag tcc ggc 288 Tyr Arg Val Met Leu Gly Gln His Asn
Leu Tyr Val Ala Glu Ser Gly 85 90 95 tcg ctg gcc gtc agt gtc tct
aag att gtg gtg cac aag gac tgg aac 336 Ser Leu Ala Val Ser Val Ser
Lys Ile Val Val His Lys Asp Trp Asn 100 105 110 tcc gac cag gtc tcc
aaa ggg aac gac att gcc ctg ctc aaa ctg gct 384 Ser Asp Gln Val Ser
Lys Gly Asn Asp Ile Ala Leu Leu Lys Leu Ala 115 120 125 aac ccc gtc
tcc ctc acc gac aag atc cag ctg gcc tgc ctc cct cct 432 Asn Pro Val
Ser Leu Thr Asp Lys Ile Gln Leu Ala Cys Leu Pro Pro 130 135 140 gcc
ggc acc att cta ccc aac aac tac ccc tgc tac gtc acg ggc tgg 480 Ala
Gly Thr Ile Leu Pro Asn Asn Tyr Pro Cys Tyr Val Thr Gly Trp 145 150
155 160 gga agg ctg cag acc aac ggg gct ctc cct gat gac ctg aag cag
ggc 528 Gly Arg Leu Gln Thr Asn Gly Ala Leu Pro Asp Asp Leu Lys Gln
Gly 165 170 175 cag ttg ctg gtt gtg gac tat gcc acc tgc tcc agc tct
ggc tgg tgg 576 Gln Leu Leu Val Val Asp Tyr Ala Thr Cys Ser Ser Ser
Gly Trp Trp 180 185 190 ggc agc acc gtg aag acg aat atg atc tgt gct
ggg ggt aat ggc gtg 624 Gly Ser Thr Val Lys Thr Asn Met Ile Cys Ala
Gly Gly Asn Gly Val 195 200 205 ata tgc acc tgc aac gga gac tct ggc
ggg cca ctg aac tgt cag gcg 672 Ile Cys Thr Cys Asn Gly Asp Ser Gly
Gly Pro Leu Asn Cys Gln Ala 210 215 220 tct gac ggc cgg tgg cag gtg
cac ggc atc gtc agc ttc ggg tct cgc 720 Ser Asp Gly Arg Trp Gln Val
His Gly Ile Val Ser Phe Gly Ser Arg 225 230 235 240 ctc ggc tgc aac
tac tac cac aag ccc tcc gtc ttc acg cgg gtc tcc 768 Leu Gly Cys Asn
Tyr Tyr His Lys Pro Ser Val Phe Thr Arg Val Ser 245 250 255 aat tac
atc gac tgg atg att gca aat aac taaccaaaag aagtccctgg 818 Asn Tyr
Ile Asp Trp Met Ile Ala Asn Asn 260 265 gactgtttca gacttggaaa
ggtcacggaa ggaaaataat ataataaagt 868 ggcaactatg caaaaaaaaa a 889 6
266 PRT Homo sapiens 6 Met Ile Arg Thr Leu Leu Leu Ser Thr Leu Val
Ala Gly Ala Leu Ser 1 5 10 15 Cys Gly Val Ser Thr Tyr Ala Pro Asp
Met Ser Arg Met Leu Gly Gly 20 25 30 Glu Glu Ala Arg Pro Asn Ser
Trp Pro Trp Gln Val Ser Leu Gln Tyr 35 40 45 Ser Ser Asn Gly Gln
Trp Tyr His Thr Cys Gly Gly Ser Leu Ile Ala 50 55 60 Asn Ser Trp
Val Leu Thr Ala Ala His Cys Ile Ser Ser Ser Gly Ile 65 70 75 80 Tyr
Arg Val Met Leu Gly Gln His Asn Leu Tyr Val Ala Glu Ser Gly 85 90
95 Ser Leu Ala Val Ser Val Ser Lys Ile Val Val His Lys Asp Trp Asn
100 105 110 Ser Asp Gln Val Ser Lys Gly Asn Asp Ile Ala Leu Leu Lys
Leu Ala 115 120 125 Asn Pro Val Ser Leu Thr Asp Lys Ile Gln Leu Ala
Cys Leu Pro Pro 130 135
140 Ala Gly Thr Ile Leu Pro Asn Asn Tyr Pro Cys Tyr Val Thr Gly Trp
145 150 155 160 Gly Arg Leu Gln Thr Asn Gly Ala Leu Pro Asp Asp Leu
Lys Gln Gly 165 170 175 Gln Leu Leu Val Val Asp Tyr Ala Thr Cys Ser
Ser Ser Gly Trp Trp 180 185 190 Gly Ser Thr Val Lys Thr Asn Met Ile
Cys Ala Gly Gly Asn Gly Val 195 200 205 Ile Cys Thr Cys Asn Gly Asp
Ser Gly Gly Pro Leu Asn Cys Gln Ala 210 215 220 Ser Asp Gly Arg Trp
Gln Val His Gly Ile Val Ser Phe Gly Ser Arg 225 230 235 240 Leu Gly
Cys Asn Tyr Tyr His Lys Pro Ser Val Phe Thr Arg Val Ser 245 250 255
Asn Tyr Ile Asp Trp Met Ile Ala Asn Asn 260 265 7 1188 DNA Homo
sapiens CDS (1)..(868) 7 atg att agg acc ctg ctg ctg tcc act ttg
gtg gct gga gcc ctc agt 48 Met Ile Arg Thr Leu Leu Leu Ser Thr Leu
Val Ala Gly Ala Leu Ser 1 5 10 15 tgt ggg gac ccc act tac cca cct
tat gtg act agg gtg gtt ggc ggt 96 Cys Gly Asp Pro Thr Tyr Pro Pro
Tyr Val Thr Arg Val Val Gly Gly 20 25 30 gaa gaa gcg agg ccc aac
agc tgg ccc tgg cag gtg agt ctg cag tac 144 Glu Glu Ala Arg Pro Asn
Ser Trp Pro Trp Gln Val Ser Leu Gln Tyr 35 40 45 agc tcc aat ggc
cag tgg tac cac acc tgc gga ggg tcc ctg ata gcc 192 Ser Ser Asn Gly
Gln Trp Tyr His Thr Cys Gly Gly Ser Leu Ile Ala 50 55 60 aac agc
tgg gtc ctg acg gct gcc cac tgc atc agc tcc tcc ggg atc 240 Asn Ser
Trp Val Leu Thr Ala Ala His Cys Ile Ser Ser Ser Gly Ile 65 70 75 80
tac cgc gtg atg ctg ggc cag cat aac ctc tac gtt gca gag tcc ggc 288
Tyr Arg Val Met Leu Gly Gln His Asn Leu Tyr Val Ala Glu Ser Gly 85
90 95 tcg ctg gcc gtc agt gtc tct aag att gtg gtg cac aag gac tgg
aac 336 Ser Leu Ala Val Ser Val Ser Lys Ile Val Val His Lys Asp Trp
Asn 100 105 110 tcc gac cag gtc tcc aaa ggg aac gac att gcc ctg ctc
aaa ctg gct 384 Ser Asp Gln Val Ser Lys Gly Asn Asp Ile Ala Leu Leu
Lys Leu Ala 115 120 125 aac ccc gtc tcc ctc acc gac aag atc cag ctg
gcc tgc ctc cct cct 432 Asn Pro Val Ser Leu Thr Asp Lys Ile Gln Leu
Ala Cys Leu Pro Pro 130 135 140 gcc ggc acc att cta ccc aac aac tac
ccc tgc tac gtc acg ggc tgg 480 Ala Gly Thr Ile Leu Pro Asn Asn Tyr
Pro Cys Tyr Val Thr Gly Trp 145 150 155 160 gga agg ctg cag gcc aac
ggg gct ctc cct gat gac ctg aag cag ggc 528 Gly Arg Leu Gln Ala Asn
Gly Ala Leu Pro Asp Asp Leu Lys Gln Gly 165 170 175 cag ttg ctg gtt
gtg gac tat gcc acc tgc tcc agc tct ggc tgg tgg 576 Gln Leu Leu Val
Val Asp Tyr Ala Thr Cys Ser Ser Ser Gly Trp Trp 180 185 190 ggc agc
acc gtg aag acg aat atg atc tgt gct ggg ggt aat ggc gtg 624 Gly Ser
Thr Val Lys Thr Asn Met Ile Cys Ala Gly Gly Asn Gly Val 195 200 205
ata tgc acc tgc aac gga gac tct ggc ggg cca ctg aac tgt cag gcg 672
Ile Cys Thr Cys Asn Gly Asp Ser Gly Gly Pro Leu Asn Cys Gln Ala 210
215 220 tct gac ggc cgg tgg cag gtg cac ggc atc gtc agc ttc ggg tct
cgc 720 Ser Asp Gly Arg Trp Gln Val His Gly Ile Val Ser Phe Gly Ser
Arg 225 230 235 240 ctc ggc tgc aac tac tac cac aag ccc tcc gtc ttc
acg cgg gtc tcc 768 Leu Gly Cys Asn Tyr Tyr His Lys Pro Ser Val Phe
Thr Arg Val Ser 245 250 255 aat tac atc gac tgg atc aat tcg gta aga
acc gga cca gcc ttg agc 816 Asn Tyr Ile Asp Trp Ile Asn Ser Val Arg
Thr Gly Pro Ala Leu Ser 260 265 270 ccc aag gca cta ccc tgc tca cct
ggc ctc ggg agt gcc atg ccc acc 864 Pro Lys Ala Leu Pro Cys Ser Pro
Gly Leu Gly Ser Ala Met Pro Thr 275 280 285 tgg tgactgagaa
tcccctcctt cctcttgaga gctagatggg aaccccttgg 917 Trp aggaggctgc
agacctgagt aactgctggg cctgccatgg gtcccccaaa 967 tttctgtgtg
gataaagctg agtgaaaagg aacatagagg gtggccttgt 1017 ccaaagaggt
tggacactcc tcaggcatat gaagagtgag ttccgctggg 1067 cgccgtggct
catgcctgta atcccagctc tttgggaggc caaggcgggc 1117 agatcacgag
gtcagaagtt caagaccagc ctgaccaacc tggcaaaacc 1167 ccatgtctac
taaaaaaatc c 1188 8 289 PRT Homo sapiens 8 Met Ile Arg Thr Leu Leu
Leu Ser Thr Leu Val Ala Gly Ala Leu Ser 1 5 10 15 Cys Gly Asp Pro
Thr Tyr Pro Pro Tyr Val Thr Arg Val Val Gly Gly 20 25 30 Glu Glu
Ala Arg Pro Asn Ser Trp Pro Trp Gln Val Ser Leu Gln Tyr 35 40 45
Ser Ser Asn Gly Gln Trp Tyr His Thr Cys Gly Gly Ser Leu Ile Ala 50
55 60 Asn Ser Trp Val Leu Thr Ala Ala His Cys Ile Ser Ser Ser Gly
Ile 65 70 75 80 Tyr Arg Val Met Leu Gly Gln His Asn Leu Tyr Val Ala
Glu Ser Gly 85 90 95 Ser Leu Ala Val Ser Val Ser Lys Ile Val Val
His Lys Asp Trp Asn 100 105 110 Ser Asp Gln Val Ser Lys Gly Asn Asp
Ile Ala Leu Leu Lys Leu Ala 115 120 125 Asn Pro Val Ser Leu Thr Asp
Lys Ile Gln Leu Ala Cys Leu Pro Pro 130 135 140 Ala Gly Thr Ile Leu
Pro Asn Asn Tyr Pro Cys Tyr Val Thr Gly Trp 145 150 155 160 Gly Arg
Leu Gln Ala Asn Gly Ala Leu Pro Asp Asp Leu Lys Gln Gly 165 170 175
Gln Leu Leu Val Val Asp Tyr Ala Thr Cys Ser Ser Ser Gly Trp Trp 180
185 190 Gly Ser Thr Val Lys Thr Asn Met Ile Cys Ala Gly Gly Asn Gly
Val 195 200 205 Ile Cys Thr Cys Asn Gly Asp Ser Gly Gly Pro Leu Asn
Cys Gln Ala 210 215 220 Ser Asp Gly Arg Trp Gln Val His Gly Ile Val
Ser Phe Gly Ser Arg 225 230 235 240 Leu Gly Cys Asn Tyr Tyr His Lys
Pro Ser Val Phe Thr Arg Val Ser 245 250 255 Asn Tyr Ile Asp Trp Ile
Asn Ser Val Arg Thr Gly Pro Ala Leu Ser 260 265 270 Pro Lys Ala Leu
Pro Cys Ser Pro Gly Leu Gly Ser Ala Met Pro Thr 275 280 285 Trp 9
889 DNA Homo sapiens CDS (1)..(799) 9 atg att agg acc ctg ctg ctg
tcc act ttg gtg gct gga gcc ctc agt 48 Met Ile Arg Thr Leu Leu Leu
Ser Thr Leu Val Ala Gly Ala Leu Ser 1 5 10 15 tgt ggg gac ccc act
tac cca cct tat gtg act agg gtg gtt ggc ggt 96 Cys Gly Asp Pro Thr
Tyr Pro Pro Tyr Val Thr Arg Val Val Gly Gly 20 25 30 gaa gaa gcg
agg ccc aac agc tgg ccc tgg cag gtg agt ctg cag tac 144 Glu Glu Ala
Arg Pro Asn Ser Trp Pro Trp Gln Val Ser Leu Gln Tyr 35 40 45 agc
tcc aat ggc cag tgg tac cac acc tgc gga ggg tcc ctg ata gcc 192 Ser
Ser Asn Gly Gln Trp Tyr His Thr Cys Gly Gly Ser Leu Ile Ala 50 55
60 aac agc tgg gtc ctg acg gct gcc cac tgc atc agc tcc tcc ggg atc
240 Asn Ser Trp Val Leu Thr Ala Ala His Cys Ile Ser Ser Ser Gly Ile
65 70 75 80 tac cgc gtg atg ctg ggc cag cat aac ctc tac gtt gca gag
tcc ggc 288 Tyr Arg Val Met Leu Gly Gln His Asn Leu Tyr Val Ala Glu
Ser Gly 85 90 95 tcg ctg gcc gtc agt gtc tct aag att gtg gtg cac
aag gac tgg aac 336 Ser Leu Ala Val Ser Val Ser Lys Ile Val Val His
Lys Asp Trp Asn 100 105 110 tcc gac cag gtc tcc aaa ggg aac gac att
gcc ctg ctc aaa ctg gct 384 Ser Asp Gln Val Ser Lys Gly Asn Asp Ile
Ala Leu Leu Lys Leu Ala 115 120 125 aac ccc gtc tcc ctc acc gac aag
atc cag ctg gcc tgc ctc cct cct 432 Asn Pro Val Ser Leu Thr Asp Lys
Ile Gln Leu Ala Cys Leu Pro Pro 130 135 140 gcc ggc acc att cta ccc
aac aac tac ccc tgc tac gtc acg ggc tgg 480 Ala Gly Thr Ile Leu Pro
Asn Asn Tyr Pro Cys Tyr Val Thr Gly Trp 145 150 155 160 gga agg ctg
cag gcc aac ggg gct ctc cct gat gac ctg aag cag ggc 528 Gly Arg Leu
Gln Ala Asn Gly Ala Leu Pro Asp Asp Leu Lys Gln Gly 165 170 175 cag
ttg ctg gtt gtg gac tat gcc acc tgc tcc agc tct ggc tgg tgg 576 Gln
Leu Leu Val Val Asp Tyr Ala Thr Cys Ser Ser Ser Gly Trp Trp 180 185
190 ggc agc acc gtg aag acg aat atg atc tgt gct ggg ggt aat ggc gtg
624 Gly Ser Thr Val Lys Thr Asn Met Ile Cys Ala Gly Gly Asn Gly Val
195 200 205 ata tgc acc tgc aac gga gac tct ggc ggg cca ctg aac tgt
cag gcg 672 Ile Cys Thr Cys Asn Gly Asp Ser Gly Gly Pro Leu Asn Cys
Gln Ala 210 215 220 tct gac ggc cgg tgg cag gtg cac ggc atc gtc agc
ttc ggg tct cgc 720 Ser Asp Gly Arg Trp Gln Val His Gly Ile Val Ser
Phe Gly Ser Arg 225 230 235 240 ctc ggc tgc aac tac tac cac aag ccc
tcc gtc ttc acg cgg gtc tcc 768 Leu Gly Cys Asn Tyr Tyr His Lys Pro
Ser Val Phe Thr Arg Val Ser 245 250 255 aat tac atc gac tgg atg att
gca aat aac taaccaaaag aagtccctgg 818 Asn Tyr Ile Asp Trp Met Ile
Ala Asn Asn 260 265 gactgtttca gacttggaaa ggtcacggaa ggaaaataat
ataataaagt 868 ggcaactatg caaaaaaaaa a 889 10 266 PRT Homo sapiens
10 Met Ile Arg Thr Leu Leu Leu Ser Thr Leu Val Ala Gly Ala Leu Ser
1 5 10 15 Cys Gly Asp Pro Thr Tyr Pro Pro Tyr Val Thr Arg Val Val
Gly Gly 20 25 30 Glu Glu Ala Arg Pro Asn Ser Trp Pro Trp Gln Val
Ser Leu Gln Tyr 35 40 45 Ser Ser Asn Gly Gln Trp Tyr His Thr Cys
Gly Gly Ser Leu Ile Ala 50 55 60 Asn Ser Trp Val Leu Thr Ala Ala
His Cys Ile Ser Ser Ser Gly Ile 65 70 75 80 Tyr Arg Val Met Leu Gly
Gln His Asn Leu Tyr Val Ala Glu Ser Gly 85 90 95 Ser Leu Ala Val
Ser Val Ser Lys Ile Val Val His Lys Asp Trp Asn 100 105 110 Ser Asp
Gln Val Ser Lys Gly Asn Asp Ile Ala Leu Leu Lys Leu Ala 115 120 125
Asn Pro Val Ser Leu Thr Asp Lys Ile Gln Leu Ala Cys Leu Pro Pro 130
135 140 Ala Gly Thr Ile Leu Pro Asn Asn Tyr Pro Cys Tyr Val Thr Gly
Trp 145 150 155 160 Gly Arg Leu Gln Ala Asn Gly Ala Leu Pro Asp Asp
Leu Lys Gln Gly 165 170 175 Gln Leu Leu Val Val Asp Tyr Ala Thr Cys
Ser Ser Ser Gly Trp Trp 180 185 190 Gly Ser Thr Val Lys Thr Asn Met
Ile Cys Ala Gly Gly Asn Gly Val 195 200 205 Ile Cys Thr Cys Asn Gly
Asp Ser Gly Gly Pro Leu Asn Cys Gln Ala 210 215 220 Ser Asp Gly Arg
Trp Gln Val His Gly Ile Val Ser Phe Gly Ser Arg 225 230 235 240 Leu
Gly Cys Asn Tyr Tyr His Lys Pro Ser Val Phe Thr Arg Val Ser 245 250
255 Asn Tyr Ile Asp Trp Met Ile Ala Asn Asn 260 265 11 1080 DNA
Homo sapiens CDS (1)..(1080) 11 gga tcc gtc tcc act tac gcg cct gat
atg tct agg atg ctt gga ggt 48 Gly Ser Val Ser Thr Tyr Ala Pro Asp
Met Ser Arg Met Leu Gly Gly 1 5 10 15 gaa gaa gcg agg ccc aac agc
tgg ccc tgg cag atc tcc ctg cag tac 96 Glu Glu Ala Arg Pro Asn Ser
Trp Pro Trp Gln Ile Ser Leu Gln Tyr 20 25 30 agc tcc aat ggc cag
tgg tac cac acc tgc gga ggg tcc ctg ata gcc 144 Ser Ser Asn Gly Gln
Trp Tyr His Thr Cys Gly Gly Ser Leu Ile Ala 35 40 45 aac agc tgg
gtc ctg acg gct gcc cac tgc atc agc tcc tcc ggg atc 192 Asn Ser Trp
Val Leu Thr Ala Ala His Cys Ile Ser Ser Ser Gly Ile 50 55 60 tac
cgc gtg atg ctg ggc cag cat aac ctc tac gtt gca gag tcc ggc 240 Tyr
Arg Val Met Leu Gly Gln His Asn Leu Tyr Val Ala Glu Ser Gly 65 70
75 80 tcg ctg gcc gtc agt gtc tct aag att gtg gtg cac aag gac tgg
aac 288 Ser Leu Ala Val Ser Val Ser Lys Ile Val Val His Lys Asp Trp
Asn 85 90 95 tcc gac cag gtc tcc aaa ggg aac gac att gcc ctg ctc
aaa ctg gct 336 Ser Asp Gln Val Ser Lys Gly Asn Asp Ile Ala Leu Leu
Lys Leu Ala 100 105 110 aac ccc gtc tcc ctc gcc gac aag atc cag ctg
gcc tgc ctc cct cct 384 Asn Pro Val Ser Leu Ala Asp Lys Ile Gln Leu
Ala Cys Leu Pro Pro 115 120 125 gcc ggc acc att cta ccc aac aac tac
ccc tgc tac gtc acg ggc tgg 432 Ala Gly Thr Ile Leu Pro Asn Asn Tyr
Pro Cys Tyr Val Thr Gly Trp 130 135 140 gga agg ctg cag acc aac ggg
gct ctc cct gat gac ctg aag cag ggc 480 Gly Arg Leu Gln Thr Asn Gly
Ala Leu Pro Asp Asp Leu Lys Gln Gly 145 150 155 160 cgg ttg ctg gtt
gtg gac tat gcc acc tgc tcc agc tct ggc tgg tgg 528 Arg Leu Leu Val
Val Asp Tyr Ala Thr Cys Ser Ser Ser Gly Trp Trp 165 170 175 ggc agc
acc gtg aag acg aat atg atc tgt gct ggg ggt gat ggc gtg 576 Gly Ser
Thr Val Lys Thr Asn Met Ile Cys Ala Gly Gly Asp Gly Val 180 185 190
ata tgc acc tgc aac gga gac tcc ggt ggg ccg ctg aac tgt cag gca 624
Ile Cys Thr Cys Asn Gly Asp Ser Gly Gly Pro Leu Asn Cys Gln Ala 195
200 205 tct gac ggc cgg tgg gag gtg cat ggc atc ggc agc ctc acg tcg
gtc 672 Ser Asp Gly Arg Trp Glu Val His Gly Ile Gly Ser Leu Thr Ser
Val 210 215 220 ctt ggt tgc aac tac tac tac aag ccc tcc atc ttc acg
cgg gtc tcc 720 Leu Gly Cys Asn Tyr Tyr Tyr Lys Pro Ser Ile Phe Thr
Arg Val Ser 225 230 235 240 aac tac aac gac tgg atc aat tcg gta aga
acc gga gca gcc ctg agc 768 Asn Tyr Asn Asp Trp Ile Asn Ser Val Arg
Thr Gly Ala Ala Leu Ser 245 250 255 ccc aag gca ctg acc tgc tca cct
ggc ctc ggg agt gcc atg ccc acc 816 Pro Lys Ala Leu Thr Cys Ser Pro
Gly Leu Gly Ser Ala Met Pro Thr 260 265 270 tgg cga ctg aga acc ccc
tcc ttc ctc ttg aga gct aga tgg gaa ccc 864 Trp Arg Leu Arg Thr Pro
Ser Phe Leu Leu Arg Ala Arg Trp Glu Pro 275 280 285 ctt gga gga ggc
tgc aga cct tgg caa ctg ctg agt ccc cca tgg gtc 912 Leu Gly Gly Gly
Cys Arg Pro Trp Gln Leu Leu Ser Pro Pro Trp Val 290 295 300 ccc aaa
att tct gtg tgg gta aag ctg agt gaa aag gaa cat gag agt 960 Pro Lys
Ile Ser Val Trp Val Lys Leu Ser Glu Lys Glu His Glu Ser 305 310 315
320 atg gcc ttg tcc aaa gac gtt gga cac tcc tca ggt acg tta aga gtg
1008 Met Ala Leu Ser Lys Asp Val Gly His Ser Ser Gly Thr Leu Arg
Val 325 330 335 agt tcc aca gga atg att tta ttt ttg tgt att tgt gtg
tgg ccc aga 1056 Ser Ser Thr Gly Met Ile Leu Phe Leu Cys Ile Cys
Val Trp Pro Arg 340 345 350 ctc tac cat cca gtg cta ctc gag 1080
Leu Tyr His Pro Val Leu Leu Glu 355 360 12 360 PRT Homo sapiens 12
Gly Ser Val Ser Thr Tyr Ala Pro Asp Met Ser Arg Met Leu Gly Gly 1 5
10 15 Glu Glu Ala Arg Pro Asn Ser Trp Pro Trp Gln Ile Ser Leu Gln
Tyr 20 25 30 Ser Ser Asn Gly Gln Trp Tyr His Thr Cys Gly Gly Ser
Leu Ile Ala 35 40 45 Asn Ser Trp Val Leu Thr Ala Ala His Cys Ile
Ser Ser Ser Gly Ile 50 55 60 Tyr Arg Val Met Leu Gly Gln His Asn
Leu Tyr Val Ala Glu Ser Gly 65 70 75 80 Ser Leu Ala Val Ser Val Ser
Lys Ile Val Val His Lys Asp Trp Asn 85 90 95 Ser Asp Gln Val Ser
Lys Gly Asn Asp Ile Ala Leu Leu Lys Leu Ala 100 105 110 Asn Pro Val
Ser Leu Ala Asp Lys Ile Gln Leu Ala Cys Leu Pro Pro 115 120 125 Ala
Gly Thr Ile Leu Pro Asn Asn Tyr Pro Cys Tyr Val Thr Gly Trp 130 135
140 Gly Arg Leu Gln Thr Asn Gly Ala Leu Pro Asp Asp Leu Lys Gln Gly
145 150 155 160 Arg Leu Leu Val Val Asp Tyr Ala Thr Cys Ser Ser Ser
Gly
Trp Trp 165 170 175 Gly Ser Thr Val Lys Thr Asn Met Ile Cys Ala Gly
Gly Asp Gly Val 180 185 190 Ile Cys Thr Cys Asn Gly Asp Ser Gly Gly
Pro Leu Asn Cys Gln Ala 195 200 205 Ser Asp Gly Arg Trp Glu Val His
Gly Ile Gly Ser Leu Thr Ser Val 210 215 220 Leu Gly Cys Asn Tyr Tyr
Tyr Lys Pro Ser Ile Phe Thr Arg Val Ser 225 230 235 240 Asn Tyr Asn
Asp Trp Ile Asn Ser Val Arg Thr Gly Ala Ala Leu Ser 245 250 255 Pro
Lys Ala Leu Thr Cys Ser Pro Gly Leu Gly Ser Ala Met Pro Thr 260 265
270 Trp Arg Leu Arg Thr Pro Ser Phe Leu Leu Arg Ala Arg Trp Glu Pro
275 280 285 Leu Gly Gly Gly Cys Arg Pro Trp Gln Leu Leu Ser Pro Pro
Trp Val 290 295 300 Pro Lys Ile Ser Val Trp Val Lys Leu Ser Glu Lys
Glu His Glu Ser 305 310 315 320 Met Ala Leu Ser Lys Asp Val Gly His
Ser Ser Gly Thr Leu Arg Val 325 330 335 Ser Ser Thr Gly Met Ile Leu
Phe Leu Cys Ile Cys Val Trp Pro Arg 340 345 350 Leu Tyr His Pro Val
Leu Leu Glu 355 360 13 1080 DNA Homo sapiens CDS (1)..(1080) 13 gga
tcc gtc tcc act tac gcg cct gat atg tct agg atg cgt gga ggt 48 Gly
Ser Val Ser Thr Tyr Ala Pro Asp Met Ser Arg Met Arg Gly Gly 1 5 10
15 gaa gaa gcg agg ccc aac agc tgg ccc tgg cag gtc tcc ctg cag tac
96 Glu Glu Ala Arg Pro Asn Ser Trp Pro Trp Gln Val Ser Leu Gln Tyr
20 25 30 agc tcc aat ggc cag tgg tac cac acc tgc gga ggg tcc ctg
ata gcc 144 Ser Ser Asn Gly Gln Trp Tyr His Thr Cys Gly Gly Ser Leu
Ile Ala 35 40 45 aac agc tgg gtc ctg acg gct gcc cac tgc atc agc
tcc tcc ggg atc 192 Asn Ser Trp Val Leu Thr Ala Ala His Cys Ile Ser
Ser Ser Gly Ile 50 55 60 tac cgc gtg atg ctg ggc cag cat aac ctc
tac gtt gca gag tcc ggc 240 Tyr Arg Val Met Leu Gly Gln His Asn Leu
Tyr Val Ala Glu Ser Gly 65 70 75 80 tcg ctg gcc gtc agt gtc tct aag
att gtg gtg cac aag gac tgg aac 288 Ser Leu Ala Val Ser Val Ser Lys
Ile Val Val His Lys Asp Trp Asn 85 90 95 tcc gac cag gtc tcc aaa
ggg aac gac att gcc ctg ctc aaa ctg gct 336 Ser Asp Gln Val Ser Lys
Gly Asn Asp Ile Ala Leu Leu Lys Leu Ala 100 105 110 aac ccc gtc tcc
ctc acc gac aag atc cag ctg gcc tgc ctc cct cct 384 Asn Pro Val Ser
Leu Thr Asp Lys Ile Gln Leu Ala Cys Leu Pro Pro 115 120 125 gcc ggc
acc att cta ccc aac aac tac ccc tgc tac gtc acg ggc tgg 432 Ala Gly
Thr Ile Leu Pro Asn Asn Tyr Pro Cys Tyr Val Thr Gly Trp 130 135 140
gga agg ctg cag acc aac ggg gct ctc cct gat gac ctg aag cag ggc 480
Gly Arg Leu Gln Thr Asn Gly Ala Leu Pro Asp Asp Leu Lys Gln Gly 145
150 155 160 cgg ttg ctg gtt gtg gac tat gcc acc tgc tcc agc tct ggc
tgg tgg 528 Arg Leu Leu Val Val Asp Tyr Ala Thr Cys Ser Ser Ser Gly
Trp Trp 165 170 175 ggc agc acc gtg aag acg aat atg atc tgt gct ggg
ggt gat ggc gtg 576 Gly Ser Thr Val Lys Thr Asn Met Ile Cys Ala Gly
Gly Asp Gly Val 180 185 190 ata tgc acc tgc aac gga gac tcc ggt ggg
ccg ctg aac tgc cag gca 624 Ile Cys Thr Cys Asn Gly Asp Ser Gly Gly
Pro Leu Asn Cys Gln Ala 195 200 205 tct gac ggc cgg tgg gag gtg cat
ggc atc ggc agc ctc acg tcg gtc 672 Ser Asp Gly Arg Trp Glu Val His
Gly Ile Gly Ser Leu Thr Ser Val 210 215 220 ctt ggt tgc aac tac tac
tac aag ccc tcc atc ttc acg cgg gtc tcc 720 Leu Gly Cys Asn Tyr Tyr
Tyr Lys Pro Ser Ile Phe Thr Arg Val Ser 225 230 235 240 aac tac aac
gac tgg atc aat tcg gta aga acc gga gca gcc ctg agt 768 Asn Tyr Asn
Asp Trp Ile Asn Ser Val Arg Thr Gly Ala Ala Leu Ser 245 250 255 ccc
aag gca ctg ccc tgc tca cct ggc ctc ggg agt gcc atg ccc acc 816 Pro
Lys Ala Leu Pro Cys Ser Pro Gly Leu Gly Ser Ala Met Pro Thr 260 265
270 tgg cga ctg aga acc ccc tcc ttc ctc ttg aga gct aga tgg gaa ccc
864 Trp Arg Leu Arg Thr Pro Ser Phe Leu Leu Arg Ala Arg Trp Glu Pro
275 280 285 ctt gga gga ggc tgc aga cct tgg caa ctg ctg agt ccc cca
tgg gtc 912 Leu Gly Gly Gly Cys Arg Pro Trp Gln Leu Leu Ser Pro Pro
Trp Val 290 295 300 ccc aaa att tct gtg tgg gta aag ctg agt gaa aag
gaa cat gag agt 960 Pro Lys Ile Ser Val Trp Val Lys Leu Ser Glu Lys
Glu His Glu Ser 305 310 315 320 atg gcc ttg tcc aaa gac gtt gga cac
tcc tca ggt atg tta aga gtg 1008 Met Ala Leu Ser Lys Asp Val Gly
His Ser Ser Gly Met Leu Arg Val 325 330 335 agt tcc aca gga atg att
tta ttt ttg tgt att tgt gaa tgg ccc aga 1056 Ser Ser Thr Gly Met
Ile Leu Phe Leu Cys Ile Cys Glu Trp Pro Arg 340 345 350 ctc tac cat
cca gtg cta ctc gag 1080 Leu Tyr His Pro Val Leu Leu Glu 355 360 14
360 PRT Homo sapiens 14 Gly Ser Val Ser Thr Tyr Ala Pro Asp Met Ser
Arg Met Arg Gly Gly 1 5 10 15 Glu Glu Ala Arg Pro Asn Ser Trp Pro
Trp Gln Val Ser Leu Gln Tyr 20 25 30 Ser Ser Asn Gly Gln Trp Tyr
His Thr Cys Gly Gly Ser Leu Ile Ala 35 40 45 Asn Ser Trp Val Leu
Thr Ala Ala His Cys Ile Ser Ser Ser Gly Ile 50 55 60 Tyr Arg Val
Met Leu Gly Gln His Asn Leu Tyr Val Ala Glu Ser Gly 65 70 75 80 Ser
Leu Ala Val Ser Val Ser Lys Ile Val Val His Lys Asp Trp Asn 85 90
95 Ser Asp Gln Val Ser Lys Gly Asn Asp Ile Ala Leu Leu Lys Leu Ala
100 105 110 Asn Pro Val Ser Leu Thr Asp Lys Ile Gln Leu Ala Cys Leu
Pro Pro 115 120 125 Ala Gly Thr Ile Leu Pro Asn Asn Tyr Pro Cys Tyr
Val Thr Gly Trp 130 135 140 Gly Arg Leu Gln Thr Asn Gly Ala Leu Pro
Asp Asp Leu Lys Gln Gly 145 150 155 160 Arg Leu Leu Val Val Asp Tyr
Ala Thr Cys Ser Ser Ser Gly Trp Trp 165 170 175 Gly Ser Thr Val Lys
Thr Asn Met Ile Cys Ala Gly Gly Asp Gly Val 180 185 190 Ile Cys Thr
Cys Asn Gly Asp Ser Gly Gly Pro Leu Asn Cys Gln Ala 195 200 205 Ser
Asp Gly Arg Trp Glu Val His Gly Ile Gly Ser Leu Thr Ser Val 210 215
220 Leu Gly Cys Asn Tyr Tyr Tyr Lys Pro Ser Ile Phe Thr Arg Val Ser
225 230 235 240 Asn Tyr Asn Asp Trp Ile Asn Ser Val Arg Thr Gly Ala
Ala Leu Ser 245 250 255 Pro Lys Ala Leu Pro Cys Ser Pro Gly Leu Gly
Ser Ala Met Pro Thr 260 265 270 Trp Arg Leu Arg Thr Pro Ser Phe Leu
Leu Arg Ala Arg Trp Glu Pro 275 280 285 Leu Gly Gly Gly Cys Arg Pro
Trp Gln Leu Leu Ser Pro Pro Trp Val 290 295 300 Pro Lys Ile Ser Val
Trp Val Lys Leu Ser Glu Lys Glu His Glu Ser 305 310 315 320 Met Ala
Leu Ser Lys Asp Val Gly His Ser Ser Gly Met Leu Arg Val 325 330 335
Ser Ser Thr Gly Met Ile Leu Phe Leu Cys Ile Cys Glu Trp Pro Arg 340
345 350 Leu Tyr His Pro Val Leu Leu Glu 355 360 15 1080 DNA Homo
sapiens CDS (1)..(1080) 15 gga tcc gtc tcc act tac gcg cct gat atg
tct agg atg ctt gga ggt 48 Gly Ser Val Ser Thr Tyr Ala Pro Asp Met
Ser Arg Met Leu Gly Gly 1 5 10 15 gaa gaa gcg agg ccc aac agc tgg
ccc tgg cag gtc tcc ctg cag tac 96 Glu Glu Ala Arg Pro Asn Ser Trp
Pro Trp Gln Val Ser Leu Gln Tyr 20 25 30 agc tcc aat ggc cag tgg
tac cac acc tgc gga ggg tcc ctg ata gcc 144 Ser Ser Asn Gly Gln Trp
Tyr His Thr Cys Gly Gly Ser Leu Ile Ala 35 40 45 aac agc tgg gtc
ctg acg gct gcc cac tgc atc agc tcc tcc agg atc 192 Asn Ser Trp Val
Leu Thr Ala Ala His Cys Ile Ser Ser Ser Arg Ile 50 55 60 tac cgc
gtg atg ctg ggc cag cat aac ctc tac gtt gca gag tcc ggc 240 Tyr Arg
Val Met Leu Gly Gln His Asn Leu Tyr Val Ala Glu Ser Gly 65 70 75 80
tcg cta gcc gtc agt gtc tct aag att gtg gtg cac aag gac tgg aac 288
Ser Leu Ala Val Ser Val Ser Lys Ile Val Val His Lys Asp Trp Asn 85
90 95 tcc aac cag gtc tcc aaa ggg aac gac att gcc ctg ctc aaa ctg
gct 336 Ser Asn Gln Val Ser Lys Gly Asn Asp Ile Ala Leu Leu Lys Leu
Ala 100 105 110 aac ccc gtc tcc ctc acc gac aag atc cag ctg gcc tgc
ctc cct cct 384 Asn Pro Val Ser Leu Thr Asp Lys Ile Gln Leu Ala Cys
Leu Pro Pro 115 120 125 gcc ggc acc att cta ccc aac aac tac ccc tgc
tac gtc aca ggc tgg 432 Ala Gly Thr Ile Leu Pro Asn Asn Tyr Pro Cys
Tyr Val Thr Gly Trp 130 135 140 gga agg ctg cag acc aac ggg gct ctc
cct gat gac ctg aag cag ggc 480 Gly Arg Leu Gln Thr Asn Gly Ala Leu
Pro Asp Asp Leu Lys Gln Gly 145 150 155 160 cgg ttg ctg gtt gtg gac
tat gcc acc tgc tcc agc tct ggc tgg tgg 528 Arg Leu Leu Val Val Asp
Tyr Ala Thr Cys Ser Ser Ser Gly Trp Trp 165 170 175 ggc agc acc gtg
aag acg aat atg att tgt gct ggg ggt gat ggc gtg 576 Gly Ser Thr Val
Lys Thr Asn Met Ile Cys Ala Gly Gly Asp Gly Val 180 185 190 ata tgc
acc tgc aac gga gac tcc ggt ggg ccg ctg aac tgt cag gca 624 Ile Cys
Thr Cys Asn Gly Asp Ser Gly Gly Pro Leu Asn Cys Gln Ala 195 200 205
tct gac ggc cgg tgg gag gtg cat ggc atc ggc agc ctc acg tcg gtc 672
Ser Asp Gly Arg Trp Glu Val His Gly Ile Gly Ser Leu Thr Ser Val 210
215 220 ctt ggt tgc aac tac tac tac aag ccc tcc atc ttc acg cgg gtc
tcc 720 Leu Gly Cys Asn Tyr Tyr Tyr Lys Pro Ser Ile Phe Thr Arg Val
Ser 225 230 235 240 aac tac aac gac tgg atc aat tcg gta aga acc gga
gca gcc ctg agc 768 Asn Tyr Asn Asp Trp Ile Asn Ser Val Arg Thr Gly
Ala Ala Leu Ser 245 250 255 ccc aag gca ctg acc tgc tca cct ggc ctc
ggg agt gcc atg ccc acc 816 Pro Lys Ala Leu Thr Cys Ser Pro Gly Leu
Gly Ser Ala Met Pro Thr 260 265 270 tgg cga ctg aga acc ccc tcc ttc
ctc ttg aga gct aga tgg gaa ccc 864 Trp Arg Leu Arg Thr Pro Ser Phe
Leu Leu Arg Ala Arg Trp Glu Pro 275 280 285 ctt gga gga ggc tgc aga
cct tgg caa ctg ctg agt ccc cca tgg gtc 912 Leu Gly Gly Gly Cys Arg
Pro Trp Gln Leu Leu Ser Pro Pro Trp Val 290 295 300 ccc aaa att tct
gtg tgg gta aag ctg agt gaa aag gaa cat gag agt 960 Pro Lys Ile Ser
Val Trp Val Lys Leu Ser Glu Lys Glu His Glu Ser 305 310 315 320 atg
gcc ttg tcc aaa gac gtt gga cac tcc tca ggt atg tta aga gtg 1008
Met Ala Leu Ser Lys Asp Val Gly His Ser Ser Gly Met Leu Arg Val 325
330 335 agt tcc aca gga atg att tta ttt ttg tgt att tgt gtg tgg ccc
aga 1056 Ser Ser Thr Gly Met Ile Leu Phe Leu Cys Ile Cys Val Trp
Pro Arg 340 345 350 ctc tac cat cca gtg cta ctc gag 1080 Leu Tyr
His Pro Val Leu Leu Glu 355 360 16 360 PRT Homo sapiens 16 Gly Ser
Val Ser Thr Tyr Ala Pro Asp Met Ser Arg Met Leu Gly Gly 1 5 10 15
Glu Glu Ala Arg Pro Asn Ser Trp Pro Trp Gln Val Ser Leu Gln Tyr 20
25 30 Ser Ser Asn Gly Gln Trp Tyr His Thr Cys Gly Gly Ser Leu Ile
Ala 35 40 45 Asn Ser Trp Val Leu Thr Ala Ala His Cys Ile Ser Ser
Ser Arg Ile 50 55 60 Tyr Arg Val Met Leu Gly Gln His Asn Leu Tyr
Val Ala Glu Ser Gly 65 70 75 80 Ser Leu Ala Val Ser Val Ser Lys Ile
Val Val His Lys Asp Trp Asn 85 90 95 Ser Asn Gln Val Ser Lys Gly
Asn Asp Ile Ala Leu Leu Lys Leu Ala 100 105 110 Asn Pro Val Ser Leu
Thr Asp Lys Ile Gln Leu Ala Cys Leu Pro Pro 115 120 125 Ala Gly Thr
Ile Leu Pro Asn Asn Tyr Pro Cys Tyr Val Thr Gly Trp 130 135 140 Gly
Arg Leu Gln Thr Asn Gly Ala Leu Pro Asp Asp Leu Lys Gln Gly 145 150
155 160 Arg Leu Leu Val Val Asp Tyr Ala Thr Cys Ser Ser Ser Gly Trp
Trp 165 170 175 Gly Ser Thr Val Lys Thr Asn Met Ile Cys Ala Gly Gly
Asp Gly Val 180 185 190 Ile Cys Thr Cys Asn Gly Asp Ser Gly Gly Pro
Leu Asn Cys Gln Ala 195 200 205 Ser Asp Gly Arg Trp Glu Val His Gly
Ile Gly Ser Leu Thr Ser Val 210 215 220 Leu Gly Cys Asn Tyr Tyr Tyr
Lys Pro Ser Ile Phe Thr Arg Val Ser 225 230 235 240 Asn Tyr Asn Asp
Trp Ile Asn Ser Val Arg Thr Gly Ala Ala Leu Ser 245 250 255 Pro Lys
Ala Leu Thr Cys Ser Pro Gly Leu Gly Ser Ala Met Pro Thr 260 265 270
Trp Arg Leu Arg Thr Pro Ser Phe Leu Leu Arg Ala Arg Trp Glu Pro 275
280 285 Leu Gly Gly Gly Cys Arg Pro Trp Gln Leu Leu Ser Pro Pro Trp
Val 290 295 300 Pro Lys Ile Ser Val Trp Val Lys Leu Ser Glu Lys Glu
His Glu Ser 305 310 315 320 Met Ala Leu Ser Lys Asp Val Gly His Ser
Ser Gly Met Leu Arg Val 325 330 335 Ser Ser Thr Gly Met Ile Leu Phe
Leu Cys Ile Cys Val Trp Pro Arg 340 345 350 Leu Tyr His Pro Val Leu
Leu Glu 355 360 17 1080 DNA Homo sapiens CDS (1)..(1080) 17 gga tcc
gtc tcc act tac gcg cct gat atg tct agg atg ctt gga ggt 48 Gly Ser
Val Ser Thr Tyr Ala Pro Asp Met Ser Arg Met Leu Gly Gly 1 5 10 15
gaa gaa gcg agg ccc aac agc tgg ccc tgg cag gtc tcc ctg cag tac 96
Glu Glu Ala Arg Pro Asn Ser Trp Pro Trp Gln Val Ser Leu Gln Tyr 20
25 30 agc tcc aat ggc cag tgg tac cac acc tgc gga ggg tcc ctg ata
gcc 144 Ser Ser Asn Gly Gln Trp Tyr His Thr Cys Gly Gly Ser Leu Ile
Ala 35 40 45 aac agc tgg gtc ctg acg gct gcc cac tgc atc agc tcc
tcc ggg atc 192 Asn Ser Trp Val Leu Thr Ala Ala His Cys Ile Ser Ser
Ser Gly Ile 50 55 60 tac cgc gtg atg ctg ggc cag cat aac ctc tac
gtt gca gag tcc ggc 240 Tyr Arg Val Met Leu Gly Gln His Asn Leu Tyr
Val Ala Glu Ser Gly 65 70 75 80 tcg ctg gcc gtc agt gtc tct aag att
gtg gtg cac aag gac tgg aac 288 Ser Leu Ala Val Ser Val Ser Lys Ile
Val Val His Lys Asp Trp Asn 85 90 95 tcc gac cag gtc tcc aaa ggg
aac gac att gcc ctg ctc aaa ctg gct 336 Ser Asp Gln Val Ser Lys Gly
Asn Asp Ile Ala Leu Leu Lys Leu Ala 100 105 110 aac ccc gtc tcc ctc
acc gac aag atc cag ctg gcc tgc ctc cct cct 384 Asn Pro Val Ser Leu
Thr Asp Lys Ile Gln Leu Ala Cys Leu Pro Pro 115 120 125 gcc ggc acc
att cta ccc aac aac tac ccc tgc tac gtc acg ggc tgg 432 Ala Gly Thr
Ile Leu Pro Asn Asn Tyr Pro Cys Tyr Val Thr Gly Trp 130 135 140 gga
agg ctg cag acc aac ggg gct ctc cct gat gac ctg aag cag ggc 480 Gly
Arg Leu Gln Thr Asn Gly Ala Leu Pro Asp Asp Leu Lys Gln Gly 145 150
155 160 cgg ttg ctg gtt gtg gac tat gcc acc tgc tcc agc tct ggc tgg
tgg 528 Arg Leu Leu Val Val Asp Tyr Ala Thr Cys Ser Ser Ser Gly Trp
Trp 165 170 175 ggc agc acc gtg aag acg aat atg atc tgt gct ggg ggt
gat ggc gtg 576 Gly Ser Thr Val Lys Thr Asn Met Ile Cys Ala Gly Gly
Asp Gly Val 180 185 190 ata tgc acc tgc aac gga gac tcc ggt ggg ccg
ctg aac tgt cag gca 624 Ile Cys Thr Cys Asn Gly Asp Ser Gly Gly Pro
Leu Asn Cys Gln Ala 195 200 205 tct gac ggc
cgg tgg gag gtg cat ggc atc ggc agc ctc acg tcg gtc 672 Ser Asp Gly
Arg Trp Glu Val His Gly Ile Gly Ser Leu Thr Ser Val 210 215 220 ctt
ggt tgc aac tac tac tac aag ccc tcc atc ttc acg cgg gtc tcc 720 Leu
Gly Cys Asn Tyr Tyr Tyr Lys Pro Ser Ile Phe Thr Arg Val Ser 225 230
235 240 aac tac aac gac tgg atc aat tcg gta aga acc gga gca gcc ctg
agc 768 Asn Tyr Asn Asp Trp Ile Asn Ser Val Arg Thr Gly Ala Ala Leu
Ser 245 250 255 ccc aag gca ctg ccc tgc tca cct ggc ctc ggg agt gcc
atg ccc acc 816 Pro Lys Ala Leu Pro Cys Ser Pro Gly Leu Gly Ser Ala
Met Pro Thr 260 265 270 tgg cga ctg aga acc ccc tcc ttc ctc ttg aga
gct aga tgg gaa ccc 864 Trp Arg Leu Arg Thr Pro Ser Phe Leu Leu Arg
Ala Arg Trp Glu Pro 275 280 285 ctt gga gga ggc tgc aga cct tgg caa
ctg ctg agt ccc cca tgg gtc 912 Leu Gly Gly Gly Cys Arg Pro Trp Gln
Leu Leu Ser Pro Pro Trp Val 290 295 300 ccc aaa att tct gtg tgg gta
aag ctg agt gaa aag gaa cat gag agt 960 Pro Lys Ile Ser Val Trp Val
Lys Leu Ser Glu Lys Glu His Glu Ser 305 310 315 320 atg gcc ttg tcc
aaa gac gtt gga cac tcc tca ggt atg tta aga gtg 1008 Met Ala Leu
Ser Lys Asp Val Gly His Ser Ser Gly Met Leu Arg Val 325 330 335 agt
tcc aca gga atg att tta ttt ttg tgt att tgt gtg tgg ccc aga 1056
Ser Ser Thr Gly Met Ile Leu Phe Leu Cys Ile Cys Val Trp Pro Arg 340
345 350 ctc tac cat cca gtg cta ctc gag 1080 Leu Tyr His Pro Val
Leu Leu Glu 355 360 18 360 PRT Homo sapiens 18 Gly Ser Val Ser Thr
Tyr Ala Pro Asp Met Ser Arg Met Leu Gly Gly 1 5 10 15 Glu Glu Ala
Arg Pro Asn Ser Trp Pro Trp Gln Val Ser Leu Gln Tyr 20 25 30 Ser
Ser Asn Gly Gln Trp Tyr His Thr Cys Gly Gly Ser Leu Ile Ala 35 40
45 Asn Ser Trp Val Leu Thr Ala Ala His Cys Ile Ser Ser Ser Gly Ile
50 55 60 Tyr Arg Val Met Leu Gly Gln His Asn Leu Tyr Val Ala Glu
Ser Gly 65 70 75 80 Ser Leu Ala Val Ser Val Ser Lys Ile Val Val His
Lys Asp Trp Asn 85 90 95 Ser Asp Gln Val Ser Lys Gly Asn Asp Ile
Ala Leu Leu Lys Leu Ala 100 105 110 Asn Pro Val Ser Leu Thr Asp Lys
Ile Gln Leu Ala Cys Leu Pro Pro 115 120 125 Ala Gly Thr Ile Leu Pro
Asn Asn Tyr Pro Cys Tyr Val Thr Gly Trp 130 135 140 Gly Arg Leu Gln
Thr Asn Gly Ala Leu Pro Asp Asp Leu Lys Gln Gly 145 150 155 160 Arg
Leu Leu Val Val Asp Tyr Ala Thr Cys Ser Ser Ser Gly Trp Trp 165 170
175 Gly Ser Thr Val Lys Thr Asn Met Ile Cys Ala Gly Gly Asp Gly Val
180 185 190 Ile Cys Thr Cys Asn Gly Asp Ser Gly Gly Pro Leu Asn Cys
Gln Ala 195 200 205 Ser Asp Gly Arg Trp Glu Val His Gly Ile Gly Ser
Leu Thr Ser Val 210 215 220 Leu Gly Cys Asn Tyr Tyr Tyr Lys Pro Ser
Ile Phe Thr Arg Val Ser 225 230 235 240 Asn Tyr Asn Asp Trp Ile Asn
Ser Val Arg Thr Gly Ala Ala Leu Ser 245 250 255 Pro Lys Ala Leu Pro
Cys Ser Pro Gly Leu Gly Ser Ala Met Pro Thr 260 265 270 Trp Arg Leu
Arg Thr Pro Ser Phe Leu Leu Arg Ala Arg Trp Glu Pro 275 280 285 Leu
Gly Gly Gly Cys Arg Pro Trp Gln Leu Leu Ser Pro Pro Trp Val 290 295
300 Pro Lys Ile Ser Val Trp Val Lys Leu Ser Glu Lys Glu His Glu Ser
305 310 315 320 Met Ala Leu Ser Lys Asp Val Gly His Ser Ser Gly Met
Leu Arg Val 325 330 335 Ser Ser Thr Gly Met Ile Leu Phe Leu Cys Ile
Cys Val Trp Pro Arg 340 345 350 Leu Tyr His Pro Val Leu Leu Glu 355
360 19 1023 DNA Homo sapiens CDS (1)..(1023) 19 gga tcc gtc tcc act
tac gcg cct gat atg tct agg atg ctt gga ggt 48 Gly Ser Val Ser Thr
Tyr Ala Pro Asp Met Ser Arg Met Leu Gly Gly 1 5 10 15 gaa gaa gcg
agg ccc aac agc cgg ccc tgg cag gtc tcc ctg cag tac 96 Glu Glu Ala
Arg Pro Asn Ser Arg Pro Trp Gln Val Ser Leu Gln Tyr 20 25 30 agc
tcc aat ggc cag tgg tac cac acc tgc gga ggg tcc ctg ata gcc 144 Ser
Ser Asn Gly Gln Trp Tyr His Thr Cys Gly Gly Ser Leu Ile Ala 35 40
45 aac agc tgg gtc ctg acg gct gcc cac tgc atc agc tcc tcc ggg atc
192 Asn Ser Trp Val Leu Thr Ala Ala His Cys Ile Ser Ser Ser Gly Ile
50 55 60 tac cgc gtg atg ctg ggc cag cat aac ctc tac gtt gca gag
tcc ggc 240 Tyr Arg Val Met Leu Gly Gln His Asn Leu Tyr Val Ala Glu
Ser Gly 65 70 75 80 tcg ctg gcc gtc agt gtc tct aag att gtg gtg cac
aag gac tgg aac 288 Ser Leu Ala Val Ser Val Ser Lys Ile Val Val His
Lys Asp Trp Asn 85 90 95 tcc gac cag gtc tcc aaa ggg aac gac att
gcc ctg ctc aaa ctg gct 336 Ser Asp Gln Val Ser Lys Gly Asn Asp Ile
Ala Leu Leu Lys Leu Ala 100 105 110 aac ccc gtc tcc ctc acc gac aag
atc cag ctg gcc tgc ctc cct cct 384 Asn Pro Val Ser Leu Thr Asp Lys
Ile Gln Leu Ala Cys Leu Pro Pro 115 120 125 gcc ggc acc att cta ccc
aac aac tac ccc tgc tac gtc acg ggc tgg 432 Ala Gly Thr Ile Leu Pro
Asn Asn Tyr Pro Cys Tyr Val Thr Gly Trp 130 135 140 gga agg ctg cag
acc aac ggg gct ctc cct gat gac ctg aag cag ggc 480 Gly Arg Leu Gln
Thr Asn Gly Ala Leu Pro Asp Asp Leu Lys Gln Gly 145 150 155 160 cgg
ttg ctg gtt gtg gac tat gcc acc tgc tcc aac tct ggc tgg tgg 528 Arg
Leu Leu Val Val Asp Tyr Ala Thr Cys Ser Asn Ser Gly Trp Trp 165 170
175 ggc agc acc gtg aag acg aat atg atc tgt gct ggg ggt gat ggc gtg
576 Gly Ser Thr Val Lys Thr Asn Met Ile Cys Ala Gly Gly Asp Gly Val
180 185 190 ata tgc acc tgc aac gga gac tcc ggt ggg ccg ctg aac tgt
cag gca 624 Ile Cys Thr Cys Asn Gly Asp Ser Gly Gly Pro Leu Asn Cys
Gln Ala 195 200 205 tct gac ggc cgg tgg gag gtg cat ggc atc ggc agc
ctc acg tcg gtc 672 Ser Asp Gly Arg Trp Glu Val His Gly Ile Gly Ser
Leu Thr Ser Val 210 215 220 ctt ggt tgc aac tac tac tac aag ccc tcc
atc ttc acg cgg gtc tcc 720 Leu Gly Cys Asn Tyr Tyr Tyr Lys Pro Ser
Ile Phe Thr Arg Val Ser 225 230 235 240 aac tac aac gac tgg atc aat
tcg gta aga acc gga gca gcc ctg agc 768 Asn Tyr Asn Asp Trp Ile Asn
Ser Val Arg Thr Gly Ala Ala Leu Ser 245 250 255 ccc aag gca ctg acc
tgc tca cct ggc ctc ggg agt gcc atg ccc acc 816 Pro Lys Ala Leu Thr
Cys Ser Pro Gly Leu Gly Ser Ala Met Pro Thr 260 265 270 tgg cga ctg
aga acc ccc tcc ttc ctc ttg aga act aga tgg gaa ccc 864 Trp Arg Leu
Arg Thr Pro Ser Phe Leu Leu Arg Thr Arg Trp Glu Pro 275 280 285 ctt
gga gga ggc tgc aga cct tgg caa ctg ctg agt ccc cca tgg gtc 912 Leu
Gly Gly Gly Cys Arg Pro Trp Gln Leu Leu Ser Pro Pro Trp Val 290 295
300 ccc aaa att tct gtg tgg gta aag ctg agt gaa aag gaa cat gag agt
960 Pro Lys Ile Ser Val Trp Val Lys Leu Ser Glu Lys Glu His Glu Ser
305 310 315 320 atg gcc ttg tcc aaa gac gtt gga cac tcc tca ggt acg
tta aga gtg 1008 Met Ala Leu Ser Lys Asp Val Gly His Ser Ser Gly
Thr Leu Arg Val 325 330 335 agt tcc aca ctc gag 1023 Ser Ser Thr
Leu Glu 340 20 341 PRT Homo sapiens 20 Gly Ser Val Ser Thr Tyr Ala
Pro Asp Met Ser Arg Met Leu Gly Gly 1 5 10 15 Glu Glu Ala Arg Pro
Asn Ser Arg Pro Trp Gln Val Ser Leu Gln Tyr 20 25 30 Ser Ser Asn
Gly Gln Trp Tyr His Thr Cys Gly Gly Ser Leu Ile Ala 35 40 45 Asn
Ser Trp Val Leu Thr Ala Ala His Cys Ile Ser Ser Ser Gly Ile 50 55
60 Tyr Arg Val Met Leu Gly Gln His Asn Leu Tyr Val Ala Glu Ser Gly
65 70 75 80 Ser Leu Ala Val Ser Val Ser Lys Ile Val Val His Lys Asp
Trp Asn 85 90 95 Ser Asp Gln Val Ser Lys Gly Asn Asp Ile Ala Leu
Leu Lys Leu Ala 100 105 110 Asn Pro Val Ser Leu Thr Asp Lys Ile Gln
Leu Ala Cys Leu Pro Pro 115 120 125 Ala Gly Thr Ile Leu Pro Asn Asn
Tyr Pro Cys Tyr Val Thr Gly Trp 130 135 140 Gly Arg Leu Gln Thr Asn
Gly Ala Leu Pro Asp Asp Leu Lys Gln Gly 145 150 155 160 Arg Leu Leu
Val Val Asp Tyr Ala Thr Cys Ser Asn Ser Gly Trp Trp 165 170 175 Gly
Ser Thr Val Lys Thr Asn Met Ile Cys Ala Gly Gly Asp Gly Val 180 185
190 Ile Cys Thr Cys Asn Gly Asp Ser Gly Gly Pro Leu Asn Cys Gln Ala
195 200 205 Ser Asp Gly Arg Trp Glu Val His Gly Ile Gly Ser Leu Thr
Ser Val 210 215 220 Leu Gly Cys Asn Tyr Tyr Tyr Lys Pro Ser Ile Phe
Thr Arg Val Ser 225 230 235 240 Asn Tyr Asn Asp Trp Ile Asn Ser Val
Arg Thr Gly Ala Ala Leu Ser 245 250 255 Pro Lys Ala Leu Thr Cys Ser
Pro Gly Leu Gly Ser Ala Met Pro Thr 260 265 270 Trp Arg Leu Arg Thr
Pro Ser Phe Leu Leu Arg Thr Arg Trp Glu Pro 275 280 285 Leu Gly Gly
Gly Cys Arg Pro Trp Gln Leu Leu Ser Pro Pro Trp Val 290 295 300 Pro
Lys Ile Ser Val Trp Val Lys Leu Ser Glu Lys Glu His Glu Ser 305 310
315 320 Met Ala Leu Ser Lys Asp Val Gly His Ser Ser Gly Thr Leu Arg
Val 325 330 335 Ser Ser Thr Leu Glu 340 21 1800 DNA Homo sapiens
CDS (16)..(1762) 21 gagcctctct tcacc atg tgc ttc gtc ccc ctg gtg
tgc tgg gtg gtg 48 Met Cys Phe Val Pro Leu Val Cys Trp Val Val 1 5
10 tgt acc tgc ctc cag cag cag ctg gag ggt ggg ggg ctg ttg aga cag
96 Cys Thr Cys Leu Gln Gln Gln Leu Glu Gly Gly Gly Leu Leu Arg Gln
15 20 25 acg tcc agg acc acc act gca gtg tac atg ctc tac ctg ctg
agt ctg 144 Thr Ser Arg Thr Thr Thr Ala Val Tyr Met Leu Tyr Leu Leu
Ser Leu 30 35 40 atg caa ccc aag ccg ggg gcc ccg cgc ctc cag ccc
cca ccc aac cag 192 Met Gln Pro Lys Pro Gly Ala Pro Arg Leu Gln Pro
Pro Pro Asn Gln 45 50 55 aga ggg ttg tgc tcc ttg gcg gca gat ggg
ctc tgg aat cag aaa atc 240 Arg Gly Leu Cys Ser Leu Ala Ala Asp Gly
Leu Trp Asn Gln Lys Ile 60 65 70 75 cta ttt gag gag cag gac ctc cgg
aag cac ggc cta gac ggg gaa gac 288 Leu Phe Glu Glu Gln Asp Leu Arg
Lys His Gly Leu Asp Gly Glu Asp 80 85 90 gtc tct gcc ttc ctc aac
atg aac atc ttc cag aag gac atc aac tgt 336 Val Ser Ala Phe Leu Asn
Met Asn Ile Phe Gln Lys Asp Ile Asn Cys 95 100 105 gag agg tac tac
agc ttc atc cac ttg agt ttc cag gaa ttc ttt gca 384 Glu Arg Tyr Tyr
Ser Phe Ile His Leu Ser Phe Gln Glu Phe Phe Ala 110 115 120 gct atg
tac tat atc ctg gac gag ggg gag ggc ggg gca ggc cca gac 432 Ala Met
Tyr Tyr Ile Leu Asp Glu Gly Glu Gly Gly Ala Gly Pro Asp 125 130 135
cag gac gtg acc agg ctg ttg acc gag tac gcg ttt tct gaa agg agc 480
Gln Asp Val Thr Arg Leu Leu Thr Glu Tyr Ala Phe Ser Glu Arg Ser 140
145 150 155 ttc ctg gca ctc acc agc cgc ttc ctg ttt gga ctc ctg aac
gag gag 528 Phe Leu Ala Leu Thr Ser Arg Phe Leu Phe Gly Leu Leu Asn
Glu Glu 160 165 170 acc agg agc cac ctg gag aag agt ctc tgc tgg aag
gtc tcg ccg cac 576 Thr Arg Ser His Leu Glu Lys Ser Leu Cys Trp Lys
Val Ser Pro His 175 180 185 atc aag atg gac ctg ttg cag tgg atc caa
agc aaa gct cag agc gac 624 Ile Lys Met Asp Leu Leu Gln Trp Ile Gln
Ser Lys Ala Gln Ser Asp 190 195 200 ggc tcc acc ctg cag cag ggc tcc
ttg gag ttc ttc agc tgc ttg tac 672 Gly Ser Thr Leu Gln Gln Gly Ser
Leu Glu Phe Phe Ser Cys Leu Tyr 205 210 215 gag atc cag gag gag gag
ttt atc cag cag gcc ctg agc cac ttc cag 720 Glu Ile Gln Glu Glu Glu
Phe Ile Gln Gln Ala Leu Ser His Phe Gln 220 225 230 235 gtg atc gtg
gtc agc aac att gcc tcc aag atg gag cac atg gtc tcc 768 Val Ile Val
Val Ser Asn Ile Ala Ser Lys Met Glu His Met Val Ser 240 245 250 tcg
ttc tgt ctg aag cgc tgc agg agc gcc cag gtg ctg cac ttg tat 816 Ser
Phe Cys Leu Lys Arg Cys Arg Ser Ala Gln Val Leu His Leu Tyr 255 260
265 ggc gcc acc tac agc gcg gac ggg gaa gac cgc gcg agg tgc tcc gca
864 Gly Ala Thr Tyr Ser Ala Asp Gly Glu Asp Arg Ala Arg Cys Ser Ala
270 275 280 gga gcg cac acg ctg ttg gtg cag ctg aga cca gag agg acc
gtt ctg 912 Gly Ala His Thr Leu Leu Val Gln Leu Arg Pro Glu Arg Thr
Val Leu 285 290 295 ctg gac gcc tac agt gaa cat ctg gca gcg gcc ctg
tgc acc aat cca 960 Leu Asp Ala Tyr Ser Glu His Leu Ala Ala Ala Leu
Cys Thr Asn Pro 300 305 310 315 aac ctg ata gag ctg tct ctg tac cga
aat gcc ctg ggc agc cgg ggg 1008 Asn Leu Ile Glu Leu Ser Leu Tyr
Arg Asn Ala Leu Gly Ser Arg Gly 320 325 330 gtg aag ctg ctc tgt caa
gga ctc aga cac ccc aac tgc aaa ctt cag 1056 Val Lys Leu Leu Cys
Gln Gly Leu Arg His Pro Asn Cys Lys Leu Gln 335 340 345 aac ctg agg
agg ctg aag agg tgc cgc atc tcc agc tca gcc tgc gag 1104 Asn Leu
Arg Arg Leu Lys Arg Cys Arg Ile Ser Ser Ser Ala Cys Glu 350 355 360
gac ctc tct gca gct ctc ata gcc aat aag aat ttg aca agg atg gat
1152 Asp Leu Ser Ala Ala Leu Ile Ala Asn Lys Asn Leu Thr Arg Met
Asp 365 370 375 ctc agt ggc aac ggc gtt gga ttc cca ggc atg atg ctg
ctt tgc gag 1200 Leu Ser Gly Asn Gly Val Gly Phe Pro Gly Met Met
Leu Leu Cys Glu 380 385 390 395 ggc ctg cgg cat ccc cag tgc agg ctg
cag atg att cag ttg agg aag 1248 Gly Leu Arg His Pro Gln Cys Arg
Leu Gln Met Ile Gln Leu Arg Lys 400 405 410 tgt cag ctg gag tcc ggg
gct tgt cag gag atg gct tct gtg ctc ggc 1296 Cys Gln Leu Glu Ser
Gly Ala Cys Gln Glu Met Ala Ser Val Leu Gly 415 420 425 acc aac cca
cat ctg gtt gag ttg gac ctg aca gga aat gca ctg gag 1344 Thr Asn
Pro His Leu Val Glu Leu Asp Leu Thr Gly Asn Ala Leu Glu 430 435 440
gat ttg ggc ctg agg tta cta tgc cag gga ctg agg cac cca gtc tgc
1392 Asp Leu Gly Leu Arg Leu Leu Cys Gln Gly Leu Arg His Pro Val
Cys 445 450 455 aga cta cgg act ttg tgg tgc agg ctg aag atc tgc cgc
ctc act gct 1440 Arg Leu Arg Thr Leu Trp Cys Arg Leu Lys Ile Cys
Arg Leu Thr Ala 460 465 470 475 gct gcc tgt gac gag ctg gcc tca act
ctc agt gtg aac cag agc ctg 1488 Ala Ala Cys Asp Glu Leu Ala Ser
Thr Leu Ser Val Asn Gln Ser Leu 480 485 490 aga gag ctg gac ctg agc
ctg aat gag ctg ggg gac ctc ggg gtg ctg 1536 Arg Glu Leu Asp Leu
Ser Leu Asn Glu Leu Gly Asp Leu Gly Val Leu 495 500 505 ctg ctg tgt
gag ggc ctc agg cat ccc acg tgc aag ctc cag acc ctg 1584 Leu Leu
Cys Glu Gly Leu Arg His Pro Thr Cys Lys Leu Gln Thr Leu 510 515 520
cgg agg ttg ggc atc tgc cgg ctg ggc tct gcc gcc tgt gag ggt ctt
1632 Arg Arg Leu Gly Ile Cys Arg Leu Gly Ser Ala Ala Cys Glu Gly
Leu 525 530 535 tct gtg gtg ctc cag gcc aac cac aac ctc cgg gag ctg
gac ttg agt 1680 Ser Val Val Leu Gln Ala Asn His Asn Leu Arg Glu
Leu Asp Leu Ser 540 545 550 555 ttc aac gac ctg gga gac tgg ggc ctg
tgg ttg ctg gct gag ggg ctg 1728 Phe Asn Asp Leu Gly Asp Trp Gly
Leu Trp Leu Leu Ala Glu Gly Leu 560
565 570 caa cat ccc gcc tgc aga ctc cag aaa ctg tgg tgagcatcgg 1771
Gln His Pro Ala Cys Arg Leu Gln Lys Leu Trp 575 580 ggagtgacgg
ggtggcagtg gtcacgttt 1800 22 582 PRT Homo sapiens 22 Met Cys Phe
Val Pro Leu Val Cys Trp Val Val Cys Thr Cys Leu Gln 1 5 10 15 Gln
Gln Leu Glu Gly Gly Gly Leu Leu Arg Gln Thr Ser Arg Thr Thr 20 25
30 Thr Ala Val Tyr Met Leu Tyr Leu Leu Ser Leu Met Gln Pro Lys Pro
35 40 45 Gly Ala Pro Arg Leu Gln Pro Pro Pro Asn Gln Arg Gly Leu
Cys Ser 50 55 60 Leu Ala Ala Asp Gly Leu Trp Asn Gln Lys Ile Leu
Phe Glu Glu Gln 65 70 75 80 Asp Leu Arg Lys His Gly Leu Asp Gly Glu
Asp Val Ser Ala Phe Leu 85 90 95 Asn Met Asn Ile Phe Gln Lys Asp
Ile Asn Cys Glu Arg Tyr Tyr Ser 100 105 110 Phe Ile His Leu Ser Phe
Gln Glu Phe Phe Ala Ala Met Tyr Tyr Ile 115 120 125 Leu Asp Glu Gly
Glu Gly Gly Ala Gly Pro Asp Gln Asp Val Thr Arg 130 135 140 Leu Leu
Thr Glu Tyr Ala Phe Ser Glu Arg Ser Phe Leu Ala Leu Thr 145 150 155
160 Ser Arg Phe Leu Phe Gly Leu Leu Asn Glu Glu Thr Arg Ser His Leu
165 170 175 Glu Lys Ser Leu Cys Trp Lys Val Ser Pro His Ile Lys Met
Asp Leu 180 185 190 Leu Gln Trp Ile Gln Ser Lys Ala Gln Ser Asp Gly
Ser Thr Leu Gln 195 200 205 Gln Gly Ser Leu Glu Phe Phe Ser Cys Leu
Tyr Glu Ile Gln Glu Glu 210 215 220 Glu Phe Ile Gln Gln Ala Leu Ser
His Phe Gln Val Ile Val Val Ser 225 230 235 240 Asn Ile Ala Ser Lys
Met Glu His Met Val Ser Ser Phe Cys Leu Lys 245 250 255 Arg Cys Arg
Ser Ala Gln Val Leu His Leu Tyr Gly Ala Thr Tyr Ser 260 265 270 Ala
Asp Gly Glu Asp Arg Ala Arg Cys Ser Ala Gly Ala His Thr Leu 275 280
285 Leu Val Gln Leu Arg Pro Glu Arg Thr Val Leu Leu Asp Ala Tyr Ser
290 295 300 Glu His Leu Ala Ala Ala Leu Cys Thr Asn Pro Asn Leu Ile
Glu Leu 305 310 315 320 Ser Leu Tyr Arg Asn Ala Leu Gly Ser Arg Gly
Val Lys Leu Leu Cys 325 330 335 Gln Gly Leu Arg His Pro Asn Cys Lys
Leu Gln Asn Leu Arg Arg Leu 340 345 350 Lys Arg Cys Arg Ile Ser Ser
Ser Ala Cys Glu Asp Leu Ser Ala Ala 355 360 365 Leu Ile Ala Asn Lys
Asn Leu Thr Arg Met Asp Leu Ser Gly Asn Gly 370 375 380 Val Gly Phe
Pro Gly Met Met Leu Leu Cys Glu Gly Leu Arg His Pro 385 390 395 400
Gln Cys Arg Leu Gln Met Ile Gln Leu Arg Lys Cys Gln Leu Glu Ser 405
410 415 Gly Ala Cys Gln Glu Met Ala Ser Val Leu Gly Thr Asn Pro His
Leu 420 425 430 Val Glu Leu Asp Leu Thr Gly Asn Ala Leu Glu Asp Leu
Gly Leu Arg 435 440 445 Leu Leu Cys Gln Gly Leu Arg His Pro Val Cys
Arg Leu Arg Thr Leu 450 455 460 Trp Cys Arg Leu Lys Ile Cys Arg Leu
Thr Ala Ala Ala Cys Asp Glu 465 470 475 480 Leu Ala Ser Thr Leu Ser
Val Asn Gln Ser Leu Arg Glu Leu Asp Leu 485 490 495 Ser Leu Asn Glu
Leu Gly Asp Leu Gly Val Leu Leu Leu Cys Glu Gly 500 505 510 Leu Arg
His Pro Thr Cys Lys Leu Gln Thr Leu Arg Arg Leu Gly Ile 515 520 525
Cys Arg Leu Gly Ser Ala Ala Cys Glu Gly Leu Ser Val Val Leu Gln 530
535 540 Ala Asn His Asn Leu Arg Glu Leu Asp Leu Ser Phe Asn Asp Leu
Gly 545 550 555 560 Asp Trp Gly Leu Trp Leu Leu Ala Glu Gly Leu Gln
His Pro Ala Cys 565 570 575 Arg Leu Gln Lys Leu Trp 580 23 1683 DNA
Homo sapiens CDS (18)..(1581) 23 gcgcgcctct cttcacc atg tgc ttc gtc
ccc ctg gtg tgc tgg gtg gtg 50 Met Cys Phe Val Pro Leu Val Cys Trp
Val Val 1 5 10 tgt acc tgc ctc cag cag cag ctg gag ggt ggg ggg ctg
ttg aga cag 98 Cys Thr Cys Leu Gln Gln Gln Leu Glu Gly Gly Gly Leu
Leu Arg Gln 15 20 25 acg tcc agg acc acc act gca gtg tac atg ctc
tac ctg ctg agt ctg 146 Thr Ser Arg Thr Thr Thr Ala Val Tyr Met Leu
Tyr Leu Leu Ser Leu 30 35 40 atg caa ccc aag ccg ggg gcc ccg cgc
ctc cag ccc cca ccc aac cag 194 Met Gln Pro Lys Pro Gly Ala Pro Arg
Leu Gln Pro Pro Pro Asn Gln 45 50 55 aga ggg ttg tgc tcc ttg gcg
gca gat ggg ctc tgg aat cag aaa atc 242 Arg Gly Leu Cys Ser Leu Ala
Ala Asp Gly Leu Trp Asn Gln Lys Ile 60 65 70 75 cta ttt gag gag cag
gac ctc cgg aag cac ggc cta gac ggg gaa gac 290 Leu Phe Glu Glu Gln
Asp Leu Arg Lys His Gly Leu Asp Gly Glu Asp 80 85 90 gtc tct gcc
ttc ctc aac atg aac atc ttc cag aag gac atc aac tgt 338 Val Ser Ala
Phe Leu Asn Met Asn Ile Phe Gln Lys Asp Ile Asn Cys 95 100 105 gag
agg tac tac agc ttc atc cac ttg agt ttc cag gaa ttc ttt gca 386 Glu
Arg Tyr Tyr Ser Phe Ile His Leu Ser Phe Gln Glu Phe Phe Ala 110 115
120 gct atg tac tat atc ctg gac gag ggg gag ggc ggg gca ggc cca gac
434 Ala Met Tyr Tyr Ile Leu Asp Glu Gly Glu Gly Gly Ala Gly Pro Asp
125 130 135 cag gac gtg acc agg ctg ttg acc gag tac gcg ttt tct gaa
agg agc 482 Gln Asp Val Thr Arg Leu Leu Thr Glu Tyr Ala Phe Ser Glu
Arg Ser 140 145 150 155 ttc ctg gca ctc acc agc cgc ttc ctg ttt gga
ctc ctg aac gag gag 530 Phe Leu Ala Leu Thr Ser Arg Phe Leu Phe Gly
Leu Leu Asn Glu Glu 160 165 170 acc agg agc cac ctg gag aag agt ctc
tgc tgg aag gtc tcg ccg cac 578 Thr Arg Ser His Leu Glu Lys Ser Leu
Cys Trp Lys Val Ser Pro His 175 180 185 atc aag atg gac ctg ttg cag
tgg atc caa agc aaa gct cag agc gac 626 Ile Lys Met Asp Leu Leu Gln
Trp Ile Gln Ser Lys Ala Gln Ser Asp 190 195 200 ggc tcc acc ctg cag
cag ggc tcc ttg gag ttc ttc agc tgc ttg tac 674 Gly Ser Thr Leu Gln
Gln Gly Ser Leu Glu Phe Phe Ser Cys Leu Tyr 205 210 215 gag atc cag
gag gag gag ttt atc cag cag gcc ctg agc cac ttc cag 722 Glu Ile Gln
Glu Glu Glu Phe Ile Gln Gln Ala Leu Ser His Phe Gln 220 225 230 235
gtg atc gtg gtc agc aac att gcc tcc aag atg gag cac atg gtc tcc 770
Val Ile Val Val Ser Asn Ile Ala Ser Lys Met Glu His Met Val Ser 240
245 250 tcg ttc tgt ctg aag cgc tgc agg agc gcc cag gtg ctg cac ttg
tat 818 Ser Phe Cys Leu Lys Arg Cys Arg Ser Ala Gln Val Leu His Leu
Tyr 255 260 265 ggc gcc acc tac agc gcg gac ggg gaa gac cgc gcg agg
tgc tcc gca 866 Gly Ala Thr Tyr Ser Ala Asp Gly Glu Asp Arg Ala Arg
Cys Ser Ala 270 275 280 gga gcg cac acg ctg ttg gtg cag ctc aga cca
gag agg acc gtt ctg 914 Gly Ala His Thr Leu Leu Val Gln Leu Arg Pro
Glu Arg Thr Val Leu 285 290 295 ctg gac gcc tac agt gaa cat ctg gca
gcg gcc ctg tgc acc aat cca 962 Leu Asp Ala Tyr Ser Glu His Leu Ala
Ala Ala Leu Cys Thr Asn Pro 300 305 310 315 aac ctg ata gag ctg tct
ctg tac cga aat gcc ctg ggc agc cgg ggg 1010 Asn Leu Ile Glu Leu
Ser Leu Tyr Arg Asn Ala Leu Gly Ser Arg Gly 320 325 330 gtg aag ctg
ctc tgt caa gga ctc aga cac ccc aac tgc aaa ctt cag 1058 Val Lys
Leu Leu Cys Gln Gly Leu Arg His Pro Asn Cys Lys Leu Gln 335 340 345
aac ctg agg ctg aag agg tgc cgc atc tcc agc tca gcc tgc gag gac
1106 Asn Leu Arg Leu Lys Arg Cys Arg Ile Ser Ser Ser Ala Cys Glu
Asp 350 355 360 ctc tct gca gct ctc ata gcc aat aag aat ttg aca agg
atg gat ctc 1154 Leu Ser Ala Ala Leu Ile Ala Asn Lys Asn Leu Thr
Arg Met Asp Leu 365 370 375 agt ggc aac ggc gtt gga ttc cca ggc atg
atg ctg ctt tgc gag ggc 1202 Ser Gly Asn Gly Val Gly Phe Pro Gly
Met Met Leu Leu Cys Glu Gly 380 385 390 395 ctg cgg cat ccc caa tgc
agg ctg cag atg att cag ctg aag atc tgc 1250 Leu Arg His Pro Gln
Cys Arg Leu Gln Met Ile Gln Leu Lys Ile Cys 400 405 410 cgc ctc act
gct gct gcc tgt gac gag ctg gcc tca act ctc agt gtg 1298 Arg Leu
Thr Ala Ala Ala Cys Asp Glu Leu Ala Ser Thr Leu Ser Val 415 420 425
aac cag agc ctg aga gag ctg gac ctg agc ctg aat gag ctg ggg gac
1346 Asn Gln Ser Leu Arg Glu Leu Asp Leu Ser Leu Asn Glu Leu Gly
Asp 430 435 440 ctc ggg gtg ctg ctg ctg tgt gag ggc ctc agg cat ccc
acg tgc aag 1394 Leu Gly Val Leu Leu Leu Cys Glu Gly Leu Arg His
Pro Thr Cys Lys 445 450 455 ctc cag acc ctg cgg ttg ggc atc tgc cgg
ctg ggc tct gcc gcc tgt 1442 Leu Gln Thr Leu Arg Leu Gly Ile Cys
Arg Leu Gly Ser Ala Ala Cys 460 465 470 475 gag ggt ctt tct gtg gtg
ctc cag gcc aac cac aac ctc cgg gag ctg 1490 Glu Gly Leu Ser Val
Val Leu Gln Ala Asn His Asn Leu Arg Glu Leu 480 485 490 gac ttg agt
ttc aac gac ctg gga gac tgg ggc ctg tgg ttg ctg gct 1538 Asp Leu
Ser Phe Asn Asp Leu Gly Asp Trp Gly Leu Trp Leu Leu Ala 495 500 505
gag ggg ctg caa cat ccc gcc tgc aga ctc cag aaa ctg tgg 1580 Glu
Gly Leu Gln His Pro Ala Cys Arg Leu Gln Lys Leu Trp 510 515 520
tgagcatcgg ggagtgacgg ggtggcagtg gtcacgtttg gacagtggaa 1630
gcgccttctc atccttcatt tttctattta tgaactatcc tgcttcacta 1680 caa
1683 24 521 PRT Homo sapiens 24 Met Cys Phe Val Pro Leu Val Cys Trp
Val Val Cys Thr Cys Leu Gln 1 5 10 15 Gln Gln Leu Glu Gly Gly Gly
Leu Leu Arg Gln Thr Ser Arg Thr Thr 20 25 30 Thr Ala Val Tyr Met
Leu Tyr Leu Leu Ser Leu Met Gln Pro Lys Pro 35 40 45 Gly Ala Pro
Arg Leu Gln Pro Pro Pro Asn Gln Arg Gly Leu Cys Ser 50 55 60 Leu
Ala Ala Asp Gly Leu Trp Asn Gln Lys Ile Leu Phe Glu Glu Gln 65 70
75 80 Asp Leu Arg Lys His Gly Leu Asp Gly Glu Asp Val Ser Ala Phe
Leu 85 90 95 Asn Met Asn Ile Phe Gln Lys Asp Ile Asn Cys Glu Arg
Tyr Tyr Ser 100 105 110 Phe Ile His Leu Ser Phe Gln Glu Phe Phe Ala
Ala Met Tyr Tyr Ile 115 120 125 Leu Asp Glu Gly Glu Gly Gly Ala Gly
Pro Asp Gln Asp Val Thr Arg 130 135 140 Leu Leu Thr Glu Tyr Ala Phe
Ser Glu Arg Ser Phe Leu Ala Leu Thr 145 150 155 160 Ser Arg Phe Leu
Phe Gly Leu Leu Asn Glu Glu Thr Arg Ser His Leu 165 170 175 Glu Lys
Ser Leu Cys Trp Lys Val Ser Pro His Ile Lys Met Asp Leu 180 185 190
Leu Gln Trp Ile Gln Ser Lys Ala Gln Ser Asp Gly Ser Thr Leu Gln 195
200 205 Gln Gly Ser Leu Glu Phe Phe Ser Cys Leu Tyr Glu Ile Gln Glu
Glu 210 215 220 Glu Phe Ile Gln Gln Ala Leu Ser His Phe Gln Val Ile
Val Val Ser 225 230 235 240 Asn Ile Ala Ser Lys Met Glu His Met Val
Ser Ser Phe Cys Leu Lys 245 250 255 Arg Cys Arg Ser Ala Gln Val Leu
His Leu Tyr Gly Ala Thr Tyr Ser 260 265 270 Ala Asp Gly Glu Asp Arg
Ala Arg Cys Ser Ala Gly Ala His Thr Leu 275 280 285 Leu Val Gln Leu
Arg Pro Glu Arg Thr Val Leu Leu Asp Ala Tyr Ser 290 295 300 Glu His
Leu Ala Ala Ala Leu Cys Thr Asn Pro Asn Leu Ile Glu Leu 305 310 315
320 Ser Leu Tyr Arg Asn Ala Leu Gly Ser Arg Gly Val Lys Leu Leu Cys
325 330 335 Gln Gly Leu Arg His Pro Asn Cys Lys Leu Gln Asn Leu Arg
Leu Lys 340 345 350 Arg Cys Arg Ile Ser Ser Ser Ala Cys Glu Asp Leu
Ser Ala Ala Leu 355 360 365 Ile Ala Asn Lys Asn Leu Thr Arg Met Asp
Leu Ser Gly Asn Gly Val 370 375 380 Gly Phe Pro Gly Met Met Leu Leu
Cys Glu Gly Leu Arg His Pro Gln 385 390 395 400 Cys Arg Leu Gln Met
Ile Gln Leu Lys Ile Cys Arg Leu Thr Ala Ala 405 410 415 Ala Cys Asp
Glu Leu Ala Ser Thr Leu Ser Val Asn Gln Ser Leu Arg 420 425 430 Glu
Leu Asp Leu Ser Leu Asn Glu Leu Gly Asp Leu Gly Val Leu Leu 435 440
445 Leu Cys Glu Gly Leu Arg His Pro Thr Cys Lys Leu Gln Thr Leu Arg
450 455 460 Leu Gly Ile Cys Arg Leu Gly Ser Ala Ala Cys Glu Gly Leu
Ser Val 465 470 475 480 Val Leu Gln Ala Asn His Asn Leu Arg Glu Leu
Asp Leu Ser Phe Asn 485 490 495 Asp Leu Gly Asp Trp Gly Leu Trp Leu
Leu Ala Glu Gly Leu Gln His 500 505 510 Pro Ala Cys Arg Leu Gln Lys
Leu Trp 515 520 25 481 DNA Homo sapiens CDS (28)..(382) 25
cttgtcttgt tccagttctc agaggga atg ctt tca att ttt ctc tat tca 51
Met Leu Ser Ile Phe Leu Tyr Ser 1 5 gta tta tgt tgg ctg tgg gtt tgt
cat aga ttg tgt gcc gtg agg gag 99 Val Leu Cys Trp Leu Trp Val Cys
His Arg Leu Cys Ala Val Arg Glu 10 15 20 ttt act ttc ctg gcc aag
aag cca ggc tgc agg ggc ctt cgg atc acc 147 Phe Thr Phe Leu Ala Lys
Lys Pro Gly Cys Arg Gly Leu Arg Ile Thr 25 30 35 40 acg gat gcc tgc
tgg ggt cgc tgt gag acc ttc tat cta tgg gga cag 195 Thr Asp Ala Cys
Trp Gly Arg Cys Glu Thr Phe Tyr Leu Trp Gly Gln 45 50 55 aaa ccc
att ctg gaa ccc ccc tat att gaa gcc cat cat cga gtc tgt 243 Lys Pro
Ile Leu Glu Pro Pro Tyr Ile Glu Ala His His Arg Val Cys 60 65 70
acc tac aac gag acc aaa cag gtg act gtc aag ctg ccc aac tgt gcc 291
Thr Tyr Asn Glu Thr Lys Gln Val Thr Val Lys Leu Pro Asn Cys Ala 75
80 85 ccg gga gtc gac ccc ttc tac acc tat ccc gtg gcc atc cgc tgt
gac 339 Pro Gly Val Asp Pro Phe Tyr Thr Tyr Pro Val Ala Ile Arg Cys
Asp 90 95 100 tgc gga gcc tgc tcc act gcc acc acg gag tgt gag acc
atc 381 Cys Gly Ala Cys Ser Thr Ala Thr Thr Glu Cys Glu Thr Ile 105
110 115 tgaggccgct agctgctctc tgcagaccca cctgtgtgag cagcacatgc 431
agttatactt cctggatgca agactgttta atttcgacca cacccatgga 481 26 118
PRT Homo sapiens 26 Met Leu Ser Ile Phe Leu Tyr Ser Val Leu Cys Trp
Leu Trp Val Cys 1 5 10 15 His Arg Leu Cys Ala Val Arg Glu Phe Thr
Phe Leu Ala Lys Lys Pro 20 25 30 Gly Cys Arg Gly Leu Arg Ile Thr
Thr Asp Ala Cys Trp Gly Arg Cys 35 40 45 Glu Thr Phe Tyr Leu Trp
Gly Gln Lys Pro Ile Leu Glu Pro Pro Tyr 50 55 60 Ile Glu Ala His
His Arg Val Cys Thr Tyr Asn Glu Thr Lys Gln Val 65 70 75 80 Thr Val
Lys Leu Pro Asn Cys Ala Pro Gly Val Asp Pro Phe Tyr Thr 85 90 95
Tyr Pro Val Ala Ile Arg Cys Asp Cys Gly Ala Cys Ser Thr Ala Thr 100
105 110 Thr Glu Cys Glu Thr Ile 115 27 682 DNA Homo sapiens CDS
(1)..(673) 27 atg aag acc ctg ttc ctg ggt gtc acg ctc ggc ctg gcc
gct gcc ctg 48 Met Lys Thr Leu Phe Leu Gly Val Thr Leu Gly Leu Ala
Ala Ala Leu 1 5 10 15 tcc ttc acc ctg gag gag gag gat gtg cat cca
gaa gaa aat cct gat 96 Ser Phe Thr Leu Glu Glu Glu Asp Val His Pro
Glu Glu Asn Pro Asp 20 25 30 gcg gaa tgg ggg cag gaa gct cat gta
cct gca gga gct gcc cag gag 144 Ala Glu Trp Gly Gln Glu Ala
His Val Pro Ala Gly Ala Ala Gln Glu 35 40 45 gga cca cta cat ctt
tta ctg caa aga cca gca cca tgg ggg cct gct 192 Gly Pro Leu His Leu
Leu Leu Gln Arg Pro Ala Pro Trp Gly Pro Ala 50 55 60 cca cat ggg
aaa gct tgt ggg tgc tcc ctg cag ggc cgt gcc gct gtc 240 Pro His Gly
Lys Ala Cys Gly Cys Ser Leu Gln Gly Arg Ala Ala Val 65 70 75 80 ccc
acg tcg gct cac ctg gcc acc tca cct gca ggt agg aat tct gat 288 Pro
Thr Ser Ala His Leu Ala Thr Ser Pro Ala Gly Arg Asn Ser Asp 85 90
95 acc aac cgg gag gcc ctg gaa gaa ttt aag aaa ttg gtg cag cgc aag
336 Thr Asn Arg Glu Ala Leu Glu Glu Phe Lys Lys Leu Val Gln Arg Lys
100 105 110 gga ctc tcg gag gag gac att ttc acg ccc ctg cag acg ggt
gag gat 384 Gly Leu Ser Glu Glu Asp Ile Phe Thr Pro Leu Gln Thr Gly
Glu Asp 115 120 125 ggc tgt gcc cag tcc cct gtg tcc ctc tgc tgt gtc
tgt ctg cta tct 432 Gly Cys Ala Gln Ser Pro Val Ser Leu Cys Cys Val
Cys Leu Leu Ser 130 135 140 cca gtg tcc cat gac ccc cat gtc ctc cca
tgt ccc ccg cat tcc cca 480 Pro Val Ser His Asp Pro His Val Leu Pro
Cys Pro Pro His Ser Pro 145 150 155 160 tgt gcc ccg agt ctc ctc gca
ggg gct ccc ggg ccc tgt tta gcg tcc 528 Cys Ala Pro Ser Leu Leu Ala
Gly Ala Pro Gly Pro Cys Leu Ala Ser 165 170 175 tcc tca ttg gag gct
ctg tgc tct ggg ctg cga tgg ggt ctg ggg ctc 576 Ser Ser Leu Glu Ala
Leu Cys Ser Gly Leu Arg Trp Gly Leu Gly Leu 180 185 190 cgc gct ctg
ggc tgc gat ggg gtc tgg ggc tcc gca ctc tgg gct gcg 624 Arg Ala Leu
Gly Cys Asp Gly Val Trp Gly Ser Ala Leu Trp Ala Ala 195 200 205 atg
ggg tct ggg gct ccg cgc tct ggg ctg cga tgg gct ctg ggg ctc 672 Met
Gly Ser Gly Ala Pro Arg Ser Gly Leu Arg Trp Ala Leu Gly Leu 210 215
220 tgagctctgg 682 28 224 PRT Homo sapiens 28 Met Lys Thr Leu Phe
Leu Gly Val Thr Leu Gly Leu Ala Ala Ala Leu 1 5 10 15 Ser Phe Thr
Leu Glu Glu Glu Asp Val His Pro Glu Glu Asn Pro Asp 20 25 30 Ala
Glu Trp Gly Gln Glu Ala His Val Pro Ala Gly Ala Ala Gln Glu 35 40
45 Gly Pro Leu His Leu Leu Leu Gln Arg Pro Ala Pro Trp Gly Pro Ala
50 55 60 Pro His Gly Lys Ala Cys Gly Cys Ser Leu Gln Gly Arg Ala
Ala Val 65 70 75 80 Pro Thr Ser Ala His Leu Ala Thr Ser Pro Ala Gly
Arg Asn Ser Asp 85 90 95 Thr Asn Arg Glu Ala Leu Glu Glu Phe Lys
Lys Leu Val Gln Arg Lys 100 105 110 Gly Leu Ser Glu Glu Asp Ile Phe
Thr Pro Leu Gln Thr Gly Glu Asp 115 120 125 Gly Cys Ala Gln Ser Pro
Val Ser Leu Cys Cys Val Cys Leu Leu Ser 130 135 140 Pro Val Ser His
Asp Pro His Val Leu Pro Cys Pro Pro His Ser Pro 145 150 155 160 Cys
Ala Pro Ser Leu Leu Ala Gly Ala Pro Gly Pro Cys Leu Ala Ser 165 170
175 Ser Ser Leu Glu Ala Leu Cys Ser Gly Leu Arg Trp Gly Leu Gly Leu
180 185 190 Arg Ala Leu Gly Cys Asp Gly Val Trp Gly Ser Ala Leu Trp
Ala Ala 195 200 205 Met Gly Ser Gly Ala Pro Arg Ser Gly Leu Arg Trp
Ala Leu Gly Leu 210 215 220 29 1178 DNA Homo sapiens CDS (4)..(994)
29 ggg atg gga aaa cta tgc ctg ggg ccg acg ctc tgc ccg gct gct gcc
48 Met Gly Lys Leu Cys Leu Gly Pro Thr Leu Cys Pro Ala Ala Ala 1 5
10 15 gct gag gaa agc cgg gac gcg gag ccc cgc cga gag ctt ctt tgc
tcc 96 Ala Glu Glu Ser Arg Asp Ala Glu Pro Arg Arg Glu Leu Leu Cys
Ser 20 25 30 gga cgc ccc tgg acg tgg cgg gca gcc gcg agg gta acc
acc atg atc 144 Gly Arg Pro Trp Thr Trp Arg Ala Ala Ala Arg Val Thr
Thr Met Ile 35 40 45 ccc tgg gtg ctc ctg gcc tgt gcc ctc ccc tgt
gct gct gac cca ctg 192 Pro Trp Val Leu Leu Ala Cys Ala Leu Pro Cys
Ala Ala Asp Pro Leu 50 55 60 ctt ggc gcc ttt gct cgc agg gac ttc
cgg aaa ggc tcc cct caa ctg 240 Leu Gly Ala Phe Ala Arg Arg Asp Phe
Arg Lys Gly Ser Pro Gln Leu 65 70 75 gtc tgc agc ctg cct ggc ccc
cag ggc cca ccc ggc ccc cca gga gcc 288 Val Cys Ser Leu Pro Gly Pro
Gln Gly Pro Pro Gly Pro Pro Gly Ala 80 85 90 95 cca ggg ccc tca gga
atg atg gga cga atg ggc ttt cct ggc aaa gac 336 Pro Gly Pro Ser Gly
Met Met Gly Arg Met Gly Phe Pro Gly Lys Asp 100 105 110 ggc caa gat
gga cac gac ggc gac cgg ggg gac agc gga gag gaa ggt 384 Gly Gln Asp
Gly His Asp Gly Asp Arg Gly Asp Ser Gly Glu Glu Gly 115 120 125 cca
cct ggc cgg aca ggt aac cgg gga aag cca gga cca aag ggc aaa 432 Pro
Pro Gly Arg Thr Gly Asn Arg Gly Lys Pro Gly Pro Lys Gly Lys 130 135
140 gcc ggg gcc att ggg cgg gct ggc ccc cgt ggc ccc aag ggg gtc aac
480 Ala Gly Ala Ile Gly Arg Ala Gly Pro Arg Gly Pro Lys Gly Val Asn
145 150 155 ggt acc ccc ggg aag cat ggc aca cca ggc aag aag ggg ccc
aag ggc 528 Gly Thr Pro Gly Lys His Gly Thr Pro Gly Lys Lys Gly Pro
Lys Gly 160 165 170 175 aag aag ggg gag cca ggc ctc cca ggc ccc tgc
agc tgt ggc agt ggc 576 Lys Lys Gly Glu Pro Gly Leu Pro Gly Pro Cys
Ser Cys Gly Ser Gly 180 185 190 cat acc aag tca gct ttc tcg gtg gca
gtg acc aag agc tac cca cgg 624 His Thr Lys Ser Ala Phe Ser Val Ala
Val Thr Lys Ser Tyr Pro Arg 195 200 205 gag cgg ctg ccc atc aag ttt
gac aag att ctg atg aac gag ggt ggc 672 Glu Arg Leu Pro Ile Lys Phe
Asp Lys Ile Leu Met Asn Glu Gly Gly 210 215 220 cac tac aat gct tcc
agc ggc aag ttc gtc tgc ggc gtg cct ggg atc 720 His Tyr Asn Ala Ser
Ser Gly Lys Phe Val Cys Gly Val Pro Gly Ile 225 230 235 tac tac ttc
acc tac gac atc acg ctg gcc aac aag cac ctg gcc atc 768 Tyr Tyr Phe
Thr Tyr Asp Ile Thr Leu Ala Asn Lys His Leu Ala Ile 240 245 250 255
ggc ctg gtg cac aac ggc cag tac cgc atc cgg acc ttt gat gcc aac 816
Gly Leu Val His Asn Gly Gln Tyr Arg Ile Arg Thr Phe Asp Ala Asn 260
265 270 acc ggc aac cac gat gtg gcc tca ggc tcc acc atc ctg gct ctc
aag 864 Thr Gly Asn His Asp Val Ala Ser Gly Ser Thr Ile Leu Ala Leu
Lys 275 280 285 cag ggt gac gaa gtt tgg ctg cag atc ttc tac tca gag
cag aac ggg 912 Gln Gly Asp Glu Val Trp Leu Gln Ile Phe Tyr Ser Glu
Gln Asn Gly 290 295 300 ctc ttc tat gac cct tac tgg aca gac agc ctc
ttt acg ggc ttc cta 960 Leu Phe Tyr Asp Pro Tyr Trp Thr Asp Ser Leu
Phe Thr Gly Phe Leu 305 310 315 atc tat gcc gac cag gat gac ccc aac
gag gta tagacatgcc 1003 Ile Tyr Ala Asp Gln Asp Asp Pro Asn Glu Val
320 325 330 acggcggtcc tccaggcagg gaacaagctt ctggacttgg gcttacagag
1053 caagacccca caactgtagg ctgggggtgg ggggtcgagt gagcggttct 1103
agcctcaggc tcacctcctc cgcctctttt ttttcccctt cattaaatcc 1153
aaaccttttt attcatccaa aaaaa 1178 30 330 PRT Homo sapiens 30 Met Gly
Lys Leu Cys Leu Gly Pro Thr Leu Cys Pro Ala Ala Ala Ala 1 5 10 15
Glu Glu Ser Arg Asp Ala Glu Pro Arg Arg Glu Leu Leu Cys Ser Gly 20
25 30 Arg Pro Trp Thr Trp Arg Ala Ala Ala Arg Val Thr Thr Met Ile
Pro 35 40 45 Trp Val Leu Leu Ala Cys Ala Leu Pro Cys Ala Ala Asp
Pro Leu Leu 50 55 60 Gly Ala Phe Ala Arg Arg Asp Phe Arg Lys Gly
Ser Pro Gln Leu Val 65 70 75 80 Cys Ser Leu Pro Gly Pro Gln Gly Pro
Pro Gly Pro Pro Gly Ala Pro 85 90 95 Gly Pro Ser Gly Met Met Gly
Arg Met Gly Phe Pro Gly Lys Asp Gly 100 105 110 Gln Asp Gly His Asp
Gly Asp Arg Gly Asp Ser Gly Glu Glu Gly Pro 115 120 125 Pro Gly Arg
Thr Gly Asn Arg Gly Lys Pro Gly Pro Lys Gly Lys Ala 130 135 140 Gly
Ala Ile Gly Arg Ala Gly Pro Arg Gly Pro Lys Gly Val Asn Gly 145 150
155 160 Thr Pro Gly Lys His Gly Thr Pro Gly Lys Lys Gly Pro Lys Gly
Lys 165 170 175 Lys Gly Glu Pro Gly Leu Pro Gly Pro Cys Ser Cys Gly
Ser Gly His 180 185 190 Thr Lys Ser Ala Phe Ser Val Ala Val Thr Lys
Ser Tyr Pro Arg Glu 195 200 205 Arg Leu Pro Ile Lys Phe Asp Lys Ile
Leu Met Asn Glu Gly Gly His 210 215 220 Tyr Asn Ala Ser Ser Gly Lys
Phe Val Cys Gly Val Pro Gly Ile Tyr 225 230 235 240 Tyr Phe Thr Tyr
Asp Ile Thr Leu Ala Asn Lys His Leu Ala Ile Gly 245 250 255 Leu Val
His Asn Gly Gln Tyr Arg Ile Arg Thr Phe Asp Ala Asn Thr 260 265 270
Gly Asn His Asp Val Ala Ser Gly Ser Thr Ile Leu Ala Leu Lys Gln 275
280 285 Gly Asp Glu Val Trp Leu Gln Ile Phe Tyr Ser Glu Gln Asn Gly
Leu 290 295 300 Phe Tyr Asp Pro Tyr Trp Thr Asp Ser Leu Phe Thr Gly
Phe Leu Ile 305 310 315 320 Tyr Ala Asp Gln Asp Asp Pro Asn Glu Val
325 330 31 1611 DNA Homo sapiens CDS (42)..(1512) 31 ggagcgtctg
ttgggtccgg gccgccggct tcgccctcgc c atg gcg ccc tgg 53 Met Ala Pro
Trp 1 ctg cag ctc ctg tcg ctg ctg ggg ctg ctc ccg ggc gca gtg gcc
gcc 101 Leu Gln Leu Leu Ser Leu Leu Gly Leu Leu Pro Gly Ala Val Ala
Ala 5 10 15 20 ccc gcc cag ccc cga gcc gcc agc ttt cag gcc tgg ggg
ccg ccg tcc 149 Pro Ala Gln Pro Arg Ala Ala Ser Phe Gln Ala Trp Gly
Pro Pro Ser 25 30 35 ccg cag ctg ctg gcg ccc acc cgc ttc gcg ctg
gag atg ttc aac cgc 197 Pro Gln Leu Leu Ala Pro Thr Arg Phe Ala Leu
Glu Met Phe Asn Arg 40 45 50 ggc cgg gct gcg ggg acg cgg gcc gtg
ctg ggc ctt gtg cgc gac cgt 245 Gly Arg Ala Ala Gly Thr Arg Ala Val
Leu Gly Leu Val Arg Asp Arg 55 60 65 ccg cgc ctc acc tac tcc tct
ctc cag gcg ggc cag ggg tcg ctg tac 293 Pro Arg Leu Thr Tyr Ser Ser
Leu Gln Ala Gly Gln Gly Ser Leu Tyr 70 75 80 tcc ctg gag gcc acc
ctg gag gag cca ccc tgc aac gac ccc atg gtg 341 Ser Leu Glu Ala Thr
Leu Glu Glu Pro Pro Cys Asn Asp Pro Met Val 85 90 95 100 tgc cgg
ctc ccc gtg tcc aag aaa acc ctg gtg act ttc aaa gtc ctg 389 Cys Arg
Leu Pro Val Ser Lys Lys Thr Leu Val Thr Phe Lys Val Leu 105 110 115
gat gag ctc ggg ggg cgc gtg ctg ctg cgg aag gac tgt ggc cca gtg 437
Asp Glu Leu Gly Gly Arg Val Leu Leu Arg Lys Asp Cys Gly Pro Val 120
125 130 gac acc aag gtt cca ggt gct ggg gag ccc aag tca gcc ttc act
cag 485 Asp Thr Lys Val Pro Gly Ala Gly Glu Pro Lys Ser Ala Phe Thr
Gln 135 140 145 ggc tca gcc atg att tct tct ctg tcc caa aac cat cca
gac aac aga 533 Gly Ser Ala Met Ile Ser Ser Leu Ser Gln Asn His Pro
Asp Asn Arg 150 155 160 aac gag act ttc agc tca gtc att tcc ctg ttg
aat gag gat ccc ctg 581 Asn Glu Thr Phe Ser Ser Val Ile Ser Leu Leu
Asn Glu Asp Pro Leu 165 170 175 180 tcc cag gac ttg cct gtg aag atg
gct tca atc ttc aag aac ttt gtc 629 Ser Gln Asp Leu Pro Val Lys Met
Ala Ser Ile Phe Lys Asn Phe Val 185 190 195 att acc tat aac cgg aca
tat gag tca aag gaa gaa gcc cgg tgg cgc 677 Ile Thr Tyr Asn Arg Thr
Tyr Glu Ser Lys Glu Glu Ala Arg Trp Arg 200 205 210 ctg tcc gtc ttt
gtc aat aac atg gtg cga gca cag aag atc cag gcc 725 Leu Ser Val Phe
Val Asn Asn Met Val Arg Ala Gln Lys Ile Gln Ala 215 220 225 ctg gac
cgt ggc aca gct cag tat gga gtc acc aag ttc agt gat ctc 773 Leu Asp
Arg Gly Thr Ala Gln Tyr Gly Val Thr Lys Phe Ser Asp Leu 230 235 240
aca gag gag gag ttc cgc act atc tac ctg aat act ctc ctg aga aaa 821
Thr Glu Glu Glu Phe Arg Thr Ile Tyr Leu Asn Thr Leu Leu Arg Lys 245
250 255 260 gag cct ggc aac aag atg aag caa gcc aag tct gtg ggt gac
ctc gcc 869 Glu Pro Gly Asn Lys Met Lys Gln Ala Lys Ser Val Gly Asp
Leu Ala 265 270 275 cca cct gaa tgg gac tgg agg agt aag ggg gct gtc
aca aaa gtc aaa 917 Pro Pro Glu Trp Asp Trp Arg Ser Lys Gly Ala Val
Thr Lys Val Lys 280 285 290 gac cag ggc atg tgt ggc tcc tgc tgg gcc
ttc tca gtc aca ggc aat 965 Asp Gln Gly Met Cys Gly Ser Cys Trp Ala
Phe Ser Val Thr Gly Asn 295 300 305 gtg gag ggc cag tgg ttt ctc aac
cag ggg acc ctg ctc tcc ctc tct 1013 Val Glu Gly Gln Trp Phe Leu
Asn Gln Gly Thr Leu Leu Ser Leu Ser 310 315 320 gaa cag gag ctc ttg
gac tgt gac aag atg gac aag gcc tgc atg ggc 1061 Glu Gln Glu Leu
Leu Asp Cys Asp Lys Met Asp Lys Ala Cys Met Gly 325 330 335 340 ggc
ttg ccc tcc aat gcc tac tcg gcc ata aag aat ttg gga ggg ctg 1109
Gly Leu Pro Ser Asn Ala Tyr Ser Ala Ile Lys Asn Leu Gly Gly Leu 345
350 355 gag aca gag gat gac tac agc tac cag ggt cac atg cag tcc tgc
aac 1157 Glu Thr Glu Asp Asp Tyr Ser Tyr Gln Gly His Met Gln Ser
Cys Asn 360 365 370 ttc tca gca gag aag gcc aag gtc tac atc aat gac
tcc gtg gag ctg 1205 Phe Ser Ala Glu Lys Ala Lys Val Tyr Ile Asn
Asp Ser Val Glu Leu 375 380 385 agc cag aac gag cag gag ctg gca gcc
tgg ctg gcc aag aga ggc cca 1253 Ser Gln Asn Glu Gln Glu Leu Ala
Ala Trp Leu Ala Lys Arg Gly Pro 390 395 400 atc tcc gtg gcc atc aat
gcc ttt ggc atg cag ttt tac cgc cac ggg 1301 Ile Ser Val Ala Ile
Asn Ala Phe Gly Met Gln Phe Tyr Arg His Gly 405 410 415 420 atc tcc
cgc cct ctc cgg ccc ctc tgc agc cct tgc gtc att gac cat 1349 Ile
Ser Arg Pro Leu Arg Pro Leu Cys Ser Pro Cys Val Ile Asp His 425 430
435 gcg gtg ttg ctt gtg ggc tac gga acc gtg agt tct gac gtt ccc ttt
1397 Ala Val Leu Leu Val Gly Tyr Gly Thr Val Ser Ser Asp Val Pro
Phe 440 445 450 tgg gcc atc aag aac agc tgg ggc act gac tgg ggt gag
aag ggt tac 1445 Trp Ala Ile Lys Asn Ser Trp Gly Thr Asp Trp Gly
Glu Lys Gly Tyr 455 460 465 tac tac ttg cat cgc ggg tcc ggg gca tgt
ggc gtg aac acc atg gcc 1493 Tyr Tyr Leu His Arg Gly Ser Gly Ala
Cys Gly Val Asn Thr Met Ala 470 475 480 agc tcg gcg gtg gtg gac
tgaagagggg cccccagctc gggacctggt 1541 Ser Ser Ala Val Val Asp 485
490 gctgatcaga gtggctgctg ccccagcctg acatgtgtcc aggcccctcc 1591
ccgggaggta cagctggcag 1611 32 490 PRT Homo sapiens 32 Met Ala Pro
Trp Leu Gln Leu Leu Ser Leu Leu Gly Leu Leu Pro Gly 1 5 10 15 Ala
Val Ala Ala Pro Ala Gln Pro Arg Ala Ala Ser Phe Gln Ala Trp 20 25
30 Gly Pro Pro Ser Pro Gln Leu Leu Ala Pro Thr Arg Phe Ala Leu Glu
35 40 45 Met Phe Asn Arg Gly Arg Ala Ala Gly Thr Arg Ala Val Leu
Gly Leu 50 55 60 Val Arg Asp Arg Pro Arg Leu Thr Tyr Ser Ser Leu
Gln Ala Gly Gln 65 70 75 80 Gly Ser Leu Tyr Ser Leu Glu Ala Thr Leu
Glu Glu Pro Pro Cys Asn 85 90 95 Asp Pro Met Val Cys Arg Leu Pro
Val Ser Lys Lys Thr Leu Val Thr 100 105 110 Phe Lys Val Leu Asp Glu
Leu Gly Gly Arg Val Leu Leu Arg Lys Asp 115 120 125 Cys Gly Pro Val
Asp Thr Lys Val Pro Gly Ala Gly Glu Pro Lys Ser 130 135 140 Ala Phe
Thr Gln Gly Ser Ala Met Ile Ser Ser Leu Ser Gln Asn His 145 150
155
160 Pro Asp Asn Arg Asn Glu Thr Phe Ser Ser Val Ile Ser Leu Leu Asn
165 170 175 Glu Asp Pro Leu Ser Gln Asp Leu Pro Val Lys Met Ala Ser
Ile Phe 180 185 190 Lys Asn Phe Val Ile Thr Tyr Asn Arg Thr Tyr Glu
Ser Lys Glu Glu 195 200 205 Ala Arg Trp Arg Leu Ser Val Phe Val Asn
Asn Met Val Arg Ala Gln 210 215 220 Lys Ile Gln Ala Leu Asp Arg Gly
Thr Ala Gln Tyr Gly Val Thr Lys 225 230 235 240 Phe Ser Asp Leu Thr
Glu Glu Glu Phe Arg Thr Ile Tyr Leu Asn Thr 245 250 255 Leu Leu Arg
Lys Glu Pro Gly Asn Lys Met Lys Gln Ala Lys Ser Val 260 265 270 Gly
Asp Leu Ala Pro Pro Glu Trp Asp Trp Arg Ser Lys Gly Ala Val 275 280
285 Thr Lys Val Lys Asp Gln Gly Met Cys Gly Ser Cys Trp Ala Phe Ser
290 295 300 Val Thr Gly Asn Val Glu Gly Gln Trp Phe Leu Asn Gln Gly
Thr Leu 305 310 315 320 Leu Ser Leu Ser Glu Gln Glu Leu Leu Asp Cys
Asp Lys Met Asp Lys 325 330 335 Ala Cys Met Gly Gly Leu Pro Ser Asn
Ala Tyr Ser Ala Ile Lys Asn 340 345 350 Leu Gly Gly Leu Glu Thr Glu
Asp Asp Tyr Ser Tyr Gln Gly His Met 355 360 365 Gln Ser Cys Asn Phe
Ser Ala Glu Lys Ala Lys Val Tyr Ile Asn Asp 370 375 380 Ser Val Glu
Leu Ser Gln Asn Glu Gln Glu Leu Ala Ala Trp Leu Ala 385 390 395 400
Lys Arg Gly Pro Ile Ser Val Ala Ile Asn Ala Phe Gly Met Gln Phe 405
410 415 Tyr Arg His Gly Ile Ser Arg Pro Leu Arg Pro Leu Cys Ser Pro
Cys 420 425 430 Val Ile Asp His Ala Val Leu Leu Val Gly Tyr Gly Thr
Val Ser Ser 435 440 445 Asp Val Pro Phe Trp Ala Ile Lys Asn Ser Trp
Gly Thr Asp Trp Gly 450 455 460 Glu Lys Gly Tyr Tyr Tyr Leu His Arg
Gly Ser Gly Ala Cys Gly Val 465 470 475 480 Asn Thr Met Ala Ser Ser
Ala Val Val Asp 485 490 33 1226 DNA Homo sapiens CDS (15)..(1215)
33 gcttcgccct cgcc atg gcg ccc tgg ctg cag ctc ctg tcg ctg ctg ggg
50 Met Ala Pro Trp Leu Gln Leu Leu Ser Leu Leu Gly 1 5 10 ctg ctc
ccg ggc gca gtg gcc gcc ccc gcc cag ccc caa gtc ctg gat 98 Leu Leu
Pro Gly Ala Val Ala Ala Pro Ala Gln Pro Gln Val Leu Asp 15 20 25
gag ctc gga aga cac gtg ctg ctg cgg aag gac tgt ggc cca gtg gac 146
Glu Leu Gly Arg His Val Leu Leu Arg Lys Asp Cys Gly Pro Val Asp 30
35 40 acc aag gtt cca ggt gct ggg gag ccc aag tca gcc ttc act cag
ggc 194 Thr Lys Val Pro Gly Ala Gly Glu Pro Lys Ser Ala Phe Thr Gln
Gly 45 50 55 60 tca gcc atg att tct tct ctg tcc caa aac cat cca gac
aac aga aac 242 Ser Ala Met Ile Ser Ser Leu Ser Gln Asn His Pro Asp
Asn Arg Asn 65 70 75 gag act ttc agc tca gtc att tcc ctg ttg aat
gag gat ccc ctg tcc 290 Glu Thr Phe Ser Ser Val Ile Ser Leu Leu Asn
Glu Asp Pro Leu Ser 80 85 90 cag gac ttg cct gtg aag atg gct tca
atc ttc aag aac ttt gtc att 338 Gln Asp Leu Pro Val Lys Met Ala Ser
Ile Phe Lys Asn Phe Val Ile 95 100 105 acc tat aac cgg aca tat gag
tca aag gaa gaa gcc cgg tgg cgc ctg 386 Thr Tyr Asn Arg Thr Tyr Glu
Ser Lys Glu Glu Ala Arg Trp Arg Leu 110 115 120 tcc gtc ttt gtc aat
aac atg gtg cga gca cag aag atc cag gcc ctg 434 Ser Val Phe Val Asn
Asn Met Val Arg Ala Gln Lys Ile Gln Ala Leu 125 130 135 140 gac cgt
ggc aca gct cag tat gga gtc acc aag ttc agt gat ctc aca 482 Asp Arg
Gly Thr Ala Gln Tyr Gly Val Thr Lys Phe Ser Asp Leu Thr 145 150 155
gag gag gag ttc cgc act atc tac ctg aat act ctc ctg agg aaa gag 530
Glu Glu Glu Phe Arg Thr Ile Tyr Leu Asn Thr Leu Leu Arg Lys Glu 160
165 170 cct ggc aac aag atg aag caa gcc aag tct gtg ggt gac ctc gcc
cca 578 Pro Gly Asn Lys Met Lys Gln Ala Lys Ser Val Gly Asp Leu Ala
Pro 175 180 185 cct gaa tgg gac tgg agg agt aag ggg gct gtc aca aaa
gtc aaa gac 626 Pro Glu Trp Asp Trp Arg Ser Lys Gly Ala Val Thr Lys
Val Lys Asp 190 195 200 cag ggc atg tgt ggc tcc tgc tgg gcc ttc tca
gtc aca ggc aat gtg 674 Gln Gly Met Cys Gly Ser Cys Trp Ala Phe Ser
Val Thr Gly Asn Val 205 210 215 220 gag ggc cag tgg ttt ctc aac cag
ggg acc ctg ctc tcc ctc tct gaa 722 Glu Gly Gln Trp Phe Leu Asn Gln
Gly Thr Leu Leu Ser Leu Ser Glu 225 230 235 cag gag ctc ttg gac tgt
gac aag atg gac aag gcc tgc atg ggc ggc 770 Gln Glu Leu Leu Asp Cys
Asp Lys Met Asp Lys Ala Cys Met Gly Gly 240 245 250 ttg ccc tcc aat
gcc tac tcg gcc ata aag aat ttg gga ggg ctg gag 818 Leu Pro Ser Asn
Ala Tyr Ser Ala Ile Lys Asn Leu Gly Gly Leu Glu 255 260 265 aca gag
gat gac tac agc tac cag ggt cac atg cag tcc tgc aac ttc 866 Thr Glu
Asp Asp Tyr Ser Tyr Gln Gly His Met Gln Ser Cys Asn Phe 270 275 280
tca gca gag aag gcc aag gtc tac atc aat gac tcc gtg gag ctg agc 914
Ser Ala Glu Lys Ala Lys Val Tyr Ile Asn Asp Ser Val Glu Leu Ser 285
290 295 300 cag aac gag cag aag ctg gca gcc tgg ctg gcc aag aga ggc
cca atc 962 Gln Asn Glu Gln Lys Leu Ala Ala Trp Leu Ala Lys Arg Gly
Pro Ile 305 310 315 tcc gtg gcc atc aat gcc ttt ggc atg cag ttt tac
cgc cac ggg atc 1010 Ser Val Ala Ile Asn Ala Phe Gly Met Gln Phe
Tyr Arg His Gly Ile 320 325 330 tcc cgc cct ctc cgg ccc ctc tgc agc
cct tgg ctc att gac cat gcg 1058 Ser Arg Pro Leu Arg Pro Leu Cys
Ser Pro Trp Leu Ile Asp His Ala 335 340 345 gtg ttg ctt gtg ggc tac
ggc aac cgc tct gac gtt ccc ttt tgg gcc 1106 Val Leu Leu Val Gly
Tyr Gly Asn Arg Ser Asp Val Pro Phe Trp Ala 350 355 360 atc aag aac
agc tgg ggc act gac tgg ggt gag aag ggt tac tac tac 1154 Ile Lys
Asn Ser Trp Gly Thr Asp Trp Gly Glu Lys Gly Tyr Tyr Tyr 365 370 375
380 ttg cat cgc ggg tcc ggg gcc tgt ggc gtg aac acc atg gcc agc tcg
1202 Leu His Arg Gly Ser Gly Ala Cys Gly Val Asn Thr Met Ala Ser
Ser 385 390 395 gcg gtg gtg gac tgaagagggg cc 1226 Ala Val Val Asp
400 34 400 PRT Homo sapiens 34 Met Ala Pro Trp Leu Gln Leu Leu Ser
Leu Leu Gly Leu Leu Pro Gly 1 5 10 15 Ala Val Ala Ala Pro Ala Gln
Pro Gln Val Leu Asp Glu Leu Gly Arg 20 25 30 His Val Leu Leu Arg
Lys Asp Cys Gly Pro Val Asp Thr Lys Val Pro 35 40 45 Gly Ala Gly
Glu Pro Lys Ser Ala Phe Thr Gln Gly Ser Ala Met Ile 50 55 60 Ser
Ser Leu Ser Gln Asn His Pro Asp Asn Arg Asn Glu Thr Phe Ser 65 70
75 80 Ser Val Ile Ser Leu Leu Asn Glu Asp Pro Leu Ser Gln Asp Leu
Pro 85 90 95 Val Lys Met Ala Ser Ile Phe Lys Asn Phe Val Ile Thr
Tyr Asn Arg 100 105 110 Thr Tyr Glu Ser Lys Glu Glu Ala Arg Trp Arg
Leu Ser Val Phe Val 115 120 125 Asn Asn Met Val Arg Ala Gln Lys Ile
Gln Ala Leu Asp Arg Gly Thr 130 135 140 Ala Gln Tyr Gly Val Thr Lys
Phe Ser Asp Leu Thr Glu Glu Glu Phe 145 150 155 160 Arg Thr Ile Tyr
Leu Asn Thr Leu Leu Arg Lys Glu Pro Gly Asn Lys 165 170 175 Met Lys
Gln Ala Lys Ser Val Gly Asp Leu Ala Pro Pro Glu Trp Asp 180 185 190
Trp Arg Ser Lys Gly Ala Val Thr Lys Val Lys Asp Gln Gly Met Cys 195
200 205 Gly Ser Cys Trp Ala Phe Ser Val Thr Gly Asn Val Glu Gly Gln
Trp 210 215 220 Phe Leu Asn Gln Gly Thr Leu Leu Ser Leu Ser Glu Gln
Glu Leu Leu 225 230 235 240 Asp Cys Asp Lys Met Asp Lys Ala Cys Met
Gly Gly Leu Pro Ser Asn 245 250 255 Ala Tyr Ser Ala Ile Lys Asn Leu
Gly Gly Leu Glu Thr Glu Asp Asp 260 265 270 Tyr Ser Tyr Gln Gly His
Met Gln Ser Cys Asn Phe Ser Ala Glu Lys 275 280 285 Ala Lys Val Tyr
Ile Asn Asp Ser Val Glu Leu Ser Gln Asn Glu Gln 290 295 300 Lys Leu
Ala Ala Trp Leu Ala Lys Arg Gly Pro Ile Ser Val Ala Ile 305 310 315
320 Asn Ala Phe Gly Met Gln Phe Tyr Arg His Gly Ile Ser Arg Pro Leu
325 330 335 Arg Pro Leu Cys Ser Pro Trp Leu Ile Asp His Ala Val Leu
Leu Val 340 345 350 Gly Tyr Gly Asn Arg Ser Asp Val Pro Phe Trp Ala
Ile Lys Asn Ser 355 360 365 Trp Gly Thr Asp Trp Gly Glu Lys Gly Tyr
Tyr Tyr Leu His Arg Gly 370 375 380 Ser Gly Ala Cys Gly Val Asn Thr
Met Ala Ser Ser Ala Val Val Asp 385 390 395 400 35 1704 DNA Homo
sapiens CDS (103)..(1666) 35 tggtagatgt ggcatttcca tgctgaggcc
gcgagtcccg cctgaccccg 50 tcgctgcctc tccagggctt ctctgggccg
cgcctctgca gactgcgcag 100 cc atg ctg cat ctg ctg gcg ctc ttc ctg
cac tgc ctc cct ctg gcc 147 Met Leu His Leu Leu Ala Leu Phe Leu His
Cys Leu Pro Leu Ala 1 5 10 15 tct ggg gac tat gac atc tgc aaa tcc
tgg gtg acc aca gat gag ggc 195 Ser Gly Asp Tyr Asp Ile Cys Lys Ser
Trp Val Thr Thr Asp Glu Gly 20 25 30 ccc acc tgg gag ttc tac gcc
tgc cag ccc aag gtg atg cgc ctg aag 243 Pro Thr Trp Glu Phe Tyr Ala
Cys Gln Pro Lys Val Met Arg Leu Lys 35 40 45 gac tac gtc aag gtg
aag gtg gag ccc tca ggc atc aca tgt gga gac 291 Asp Tyr Val Lys Val
Lys Val Glu Pro Ser Gly Ile Thr Cys Gly Asp 50 55 60 ccc cct gag
agg ttc tgc tcc cat ccc tac cta tgc agc aac gag tgt 339 Pro Pro Glu
Arg Phe Cys Ser His Pro Tyr Leu Cys Ser Asn Glu Cys 65 70 75 gac
gcc tcc aac ccg gac ctg gcc cac ccg ccc agg ctc atg ttc gac 387 Asp
Ala Ser Asn Pro Asp Leu Ala His Pro Pro Arg Leu Met Phe Asp 80 85
90 95 aag gag gag gag ggc ctg gcc acc tac tgg cag agc atc acc tgg
agc 435 Lys Glu Glu Glu Gly Leu Ala Thr Tyr Trp Gln Ser Ile Thr Trp
Ser 100 105 110 cgc tac ccc agc ccg ctg gaa gcc aac atc acc ctt tcg
tgg aac aag 483 Arg Tyr Pro Ser Pro Leu Glu Ala Asn Ile Thr Leu Ser
Trp Asn Lys 115 120 125 acc gtg gag ctg acc gac gac gtg gtg atg acc
ttc gag tac ggc cgg 531 Thr Val Glu Leu Thr Asp Asp Val Val Met Thr
Phe Glu Tyr Gly Arg 130 135 140 ccc acg gtc atg gtc ctg gag aag tcc
ctg gac aac ggg cgc acc tgg 579 Pro Thr Val Met Val Leu Glu Lys Ser
Leu Asp Asn Gly Arg Thr Trp 145 150 155 cag ccc tac cag ttc tac gcc
gag gac tgc atg gag gcc ttc ggt atg 627 Gln Pro Tyr Gln Phe Tyr Ala
Glu Asp Cys Met Glu Ala Phe Gly Met 160 165 170 175 tcc gcc cgc cgg
gcc cgc gac atg tca tcc tcc agc gcg cac cgc gtg 675 Ser Ala Arg Arg
Ala Arg Asp Met Ser Ser Ser Ser Ala His Arg Val 180 185 190 ctc tgc
acc gag gag tac tcg cgc tgg gca ggc tcc aag aag gag aag 723 Leu Cys
Thr Glu Glu Tyr Ser Arg Trp Ala Gly Ser Lys Lys Glu Lys 195 200 205
cac gtg cgc ttc gag gtg cgg gac cgc ttc gcc atc ttt gcc ggc ccc 771
His Val Arg Phe Glu Val Arg Asp Arg Phe Ala Ile Phe Ala Gly Pro 210
215 220 gac ctg cgc aac atg gac aac ctc tac acg cgg ctg gag agc gcc
aag 819 Asp Leu Arg Asn Met Asp Asn Leu Tyr Thr Arg Leu Glu Ser Ala
Lys 225 230 235 ggc ctc aag gag ttc ttc acc ctc acc gac ctg cgc atg
cgg ctg ctg 867 Gly Leu Lys Glu Phe Phe Thr Leu Thr Asp Leu Arg Met
Arg Leu Leu 240 245 250 255 cgc ccg gcg ctg ggc ggc acc tat gtg cag
cgg gag aac ctc tac aag 915 Arg Pro Ala Leu Gly Gly Thr Tyr Val Gln
Arg Glu Asn Leu Tyr Lys 260 265 270 tac ttc tac gcc atc tcc aac atc
gag gtc atc ggc agg tgc aag tgc 963 Tyr Phe Tyr Ala Ile Ser Asn Ile
Glu Val Ile Gly Arg Cys Lys Cys 275 280 285 aac ctg cac gcc aac ctg
tgc tcc atg cgc gag ggc agc ctg cag tgc 1011 Asn Leu His Ala Asn
Leu Cys Ser Met Arg Glu Gly Ser Leu Gln Cys 290 295 300 gag tgc gag
cac aac acc acc ggc ccc gac tgc ggc aag tgc aag aag 1059 Glu Cys
Glu His Asn Thr Thr Gly Pro Asp Cys Gly Lys Cys Lys Lys 305 310 315
aat ttc cgc acc cgg tcc tgg cgg gcc ggc tcc tac ctg ccg ctg ccc
1107 Asn Phe Arg Thr Arg Ser Trp Arg Ala Gly Ser Tyr Leu Pro Leu
Pro 320 325 330 335 cat ggc tct ccc aac gcc tgt gac tgc gaa tgc tac
ggt cac tcc aac 1155 His Gly Ser Pro Asn Ala Cys Asp Cys Glu Cys
Tyr Gly His Ser Asn 340 345 350 cgc tgc agc tac att gac ttc ctg aat
gtg gtg acc tgc gtc agc tgc 1203 Arg Cys Ser Tyr Ile Asp Phe Leu
Asn Val Val Thr Cys Val Ser Cys 355 360 365 aag cac aac acg cga ggt
cag cac tgc cag cac tgc cgg ctg ggc tac 1251 Lys His Asn Thr Arg
Gly Gln His Cys Gln His Cys Arg Leu Gly Tyr 370 375 380 tac cgc aac
ggc tcg gca gag ctg gat gat gag aac gtc tgc att gag 1299 Tyr Arg
Asn Gly Ser Ala Glu Leu Asp Asp Glu Asn Val Cys Ile Glu 385 390 395
tgt aac tgc aac cag ata ggc tcc gtg cac gac cgg tgc aac gag acc
1347 Cys Asn Cys Asn Gln Ile Gly Ser Val His Asp Arg Cys Asn Glu
Thr 400 405 410 415 ggc ttc tgc gag tgc cgc gag ggc gcg gcg ggc ccc
aag tgc gac gac 1395 Gly Phe Cys Glu Cys Arg Glu Gly Ala Ala Gly
Pro Lys Cys Asp Asp 420 425 430 tgc ctc ccc acg cac tac tgg cgc cag
ggc tgc tac ccc aac gtg tgc 1443 Cys Leu Pro Thr His Tyr Trp Arg
Gln Gly Cys Tyr Pro Asn Val Cys 435 440 445 gac gac gac cag ctg ctg
tgc cag aac gga ggc acc tgc ctg cag aac 1491 Asp Asp Asp Gln Leu
Leu Cys Gln Asn Gly Gly Thr Cys Leu Gln Asn 450 455 460 cag cgc tgc
gcc tgc ccg cgc ggc tac acc ggc gtg cgc tgc gag cag 1539 Gln Arg
Cys Ala Cys Pro Arg Gly Tyr Thr Gly Val Arg Cys Glu Gln 465 470 475
ccc cgc tgc gac ccc gcc gac gat gac ggc ggt ctg gac tgc gac cgc
1587 Pro Arg Cys Asp Pro Ala Asp Asp Asp Gly Gly Leu Asp Cys Asp
Arg 480 485 490 495 gcg ccc ggg gcc gcc ccg cgc ccc gcc acc ctg ctc
ggc tgc ctg ctg 1635 Ala Pro Gly Ala Ala Pro Arg Pro Ala Thr Leu
Leu Gly Cys Leu Leu 500 505 510 ctg ctg ggg ctg gcc gcc cgc ctg ggc
cgc tgagccccgc ccggaggacg 1685 Leu Leu Gly Leu Ala Ala Arg Leu Gly
Arg 515 520 ctccccgcac ccggaggcc 1704 36 521 PRT Homo sapiens 36
Met Leu His Leu Leu Ala Leu Phe Leu His Cys Leu Pro Leu Ala Ser 1 5
10 15 Gly Asp Tyr Asp Ile Cys Lys Ser Trp Val Thr Thr Asp Glu Gly
Pro 20 25 30 Thr Trp Glu Phe Tyr Ala Cys Gln Pro Lys Val Met Arg
Leu Lys Asp 35 40 45 Tyr Val Lys Val Lys Val Glu Pro Ser Gly Ile
Thr Cys Gly Asp Pro 50 55 60 Pro Glu Arg Phe Cys Ser His Pro Tyr
Leu Cys Ser Asn Glu Cys Asp 65 70 75 80 Ala Ser Asn Pro Asp Leu Ala
His Pro Pro Arg Leu Met Phe Asp Lys 85 90 95 Glu Glu Glu Gly Leu
Ala Thr Tyr Trp Gln Ser Ile Thr Trp Ser Arg 100 105 110 Tyr Pro Ser
Pro Leu Glu Ala Asn Ile Thr Leu Ser Trp Asn Lys Thr 115 120 125 Val
Glu Leu Thr Asp Asp Val Val Met Thr Phe Glu Tyr Gly Arg Pro 130 135
140 Thr Val Met Val Leu Glu Lys Ser Leu Asp Asn Gly Arg Thr Trp Gln
145 150 155 160 Pro Tyr Gln Phe Tyr Ala Glu
Asp Cys Met Glu Ala Phe Gly Met Ser 165 170 175 Ala Arg Arg Ala Arg
Asp Met Ser Ser Ser Ser Ala His Arg Val Leu 180 185 190 Cys Thr Glu
Glu Tyr Ser Arg Trp Ala Gly Ser Lys Lys Glu Lys His 195 200 205 Val
Arg Phe Glu Val Arg Asp Arg Phe Ala Ile Phe Ala Gly Pro Asp 210 215
220 Leu Arg Asn Met Asp Asn Leu Tyr Thr Arg Leu Glu Ser Ala Lys Gly
225 230 235 240 Leu Lys Glu Phe Phe Thr Leu Thr Asp Leu Arg Met Arg
Leu Leu Arg 245 250 255 Pro Ala Leu Gly Gly Thr Tyr Val Gln Arg Glu
Asn Leu Tyr Lys Tyr 260 265 270 Phe Tyr Ala Ile Ser Asn Ile Glu Val
Ile Gly Arg Cys Lys Cys Asn 275 280 285 Leu His Ala Asn Leu Cys Ser
Met Arg Glu Gly Ser Leu Gln Cys Glu 290 295 300 Cys Glu His Asn Thr
Thr Gly Pro Asp Cys Gly Lys Cys Lys Lys Asn 305 310 315 320 Phe Arg
Thr Arg Ser Trp Arg Ala Gly Ser Tyr Leu Pro Leu Pro His 325 330 335
Gly Ser Pro Asn Ala Cys Asp Cys Glu Cys Tyr Gly His Ser Asn Arg 340
345 350 Cys Ser Tyr Ile Asp Phe Leu Asn Val Val Thr Cys Val Ser Cys
Lys 355 360 365 His Asn Thr Arg Gly Gln His Cys Gln His Cys Arg Leu
Gly Tyr Tyr 370 375 380 Arg Asn Gly Ser Ala Glu Leu Asp Asp Glu Asn
Val Cys Ile Glu Cys 385 390 395 400 Asn Cys Asn Gln Ile Gly Ser Val
His Asp Arg Cys Asn Glu Thr Gly 405 410 415 Phe Cys Glu Cys Arg Glu
Gly Ala Ala Gly Pro Lys Cys Asp Asp Cys 420 425 430 Leu Pro Thr His
Tyr Trp Arg Gln Gly Cys Tyr Pro Asn Val Cys Asp 435 440 445 Asp Asp
Gln Leu Leu Cys Gln Asn Gly Gly Thr Cys Leu Gln Asn Gln 450 455 460
Arg Cys Ala Cys Pro Arg Gly Tyr Thr Gly Val Arg Cys Glu Gln Pro 465
470 475 480 Arg Cys Asp Pro Ala Asp Asp Asp Gly Gly Leu Asp Cys Asp
Arg Ala 485 490 495 Pro Gly Ala Ala Pro Arg Pro Ala Thr Leu Leu Gly
Cys Leu Leu Leu 500 505 510 Leu Gly Leu Ala Ala Arg Leu Gly Arg 515
520 37 910 DNA Homo sapiens CDS (31)..(826) 37 ggtccggggg
ggctgccggt cccgggtacc atg tgt gac ggc gcc ctg ctg 51 Met Cys Asp
Gly Ala Leu Leu 1 5 cct ccg ctc gtc ctg ccc gtg ctg ctg ctg ctg gtt
tgg gga ctg gac 99 Pro Pro Leu Val Leu Pro Val Leu Leu Leu Leu Val
Trp Gly Leu Asp 10 15 20 ccg ggc aca gct gtc ggc gac gcg gcg gcc
gac gtg gag gtg gtg ctc 147 Pro Gly Thr Ala Val Gly Asp Ala Ala Ala
Asp Val Glu Val Val Leu 25 30 35 ccg tgg cgg gtg cgc ccc gac gac
gtg cac ctg ccg ccg ctg ccc gca 195 Pro Trp Arg Val Arg Pro Asp Asp
Val His Leu Pro Pro Leu Pro Ala 40 45 50 55 gcc ccc ggg ccc cga cgg
cgg cga cgc ccc cgc acg ccc cca gcc gcc 243 Ala Pro Gly Pro Arg Arg
Arg Arg Arg Pro Arg Thr Pro Pro Ala Ala 60 65 70 ccg cgc gcc cgg
ccc gga gag cgc gcc ctg ctg ctg cac ctg ccg gcc 291 Pro Arg Ala Arg
Pro Gly Glu Arg Ala Leu Leu Leu His Leu Pro Ala 75 80 85 ttc ggg
cgc gac ctg tac ctt cag ctg cgc cgc gac ctg cgc ttc ctg 339 Phe Gly
Arg Asp Leu Tyr Leu Gln Leu Arg Arg Asp Leu Arg Phe Leu 90 95 100
tcc cga ggc ttc gag gtg gag gag gcg ggc gcg gcc cgg cgc cgc ggc 387
Ser Arg Gly Phe Glu Val Glu Glu Ala Gly Ala Ala Arg Arg Arg Gly 105
110 115 cgc ccc gcc gag ctg tgc ttc tac tcg ggc cgt gtg ctc ggc cac
ccc 435 Arg Pro Ala Glu Leu Cys Phe Tyr Ser Gly Arg Val Leu Gly His
Pro 120 125 130 135 ggc tcc ctc gtc tcg ctc agc gcc tgc ggc gcc gcc
ggc ggc ctg gta 483 Gly Ser Leu Val Ser Leu Ser Ala Cys Gly Ala Ala
Gly Gly Leu Val 140 145 150 ctg ccc gcg cca cct ccg ggt cgg ccc gtc
cgg tct gtt gcg acg cag 531 Leu Pro Ala Pro Pro Pro Gly Arg Pro Val
Arg Ser Val Ala Thr Gln 155 160 165 agt ggt cgc cgt gga ggg tgg ggg
tgg ggc gcc tct gct gga agt cca 579 Ser Gly Arg Arg Gly Gly Trp Gly
Trp Gly Ala Ser Ala Gly Ser Pro 170 175 180 gcc tcc agg gga acc gga
ggg aac ccc ctg cct ttc cac ctc tcc cca 627 Ala Ser Arg Gly Thr Gly
Gly Asn Pro Leu Pro Phe His Leu Ser Pro 185 190 195 tcc ccc acc ccg
gcc ttc ggt acc ctc tat agg caa agg ggg tgg gag 675 Ser Pro Thr Pro
Ala Phe Gly Thr Leu Tyr Arg Gln Arg Gly Trp Glu 200 205 210 215 ggg
cag cat ccc agt cca gcg cct ctg cag ccc gtg gaa ccc gcg cgg 723 Gly
Gln His Pro Ser Pro Ala Pro Leu Gln Pro Val Glu Pro Ala Arg 220 225
230 agc tgg ggt tgc gtg ggg gta tac gcc gcc cgc tct agg gag cgc aga
771 Ser Trp Gly Cys Val Gly Val Tyr Ala Ala Arg Ser Arg Glu Arg Arg
235 240 245 tct ggc agg gat gaa act gtc agg gcc ctg gac aga ggc gcc
ttg gcc 819 Ser Gly Arg Asp Glu Thr Val Arg Ala Leu Asp Arg Gly Ala
Leu Ala 250 255 260 cca atg tagagaacac tgcatctgca ccgccgtgtc
aaagtgtatg tcacgggagt 875 Pro Met 265 acctgtgtac gtgtaggtgt
tatgttcttg gactt 910 38 265 PRT Homo sapiens 38 Met Cys Asp Gly Ala
Leu Leu Pro Pro Leu Val Leu Pro Val Leu Leu 1 5 10 15 Leu Leu Val
Trp Gly Leu Asp Pro Gly Thr Ala Val Gly Asp Ala Ala 20 25 30 Ala
Asp Val Glu Val Val Leu Pro Trp Arg Val Arg Pro Asp Asp Val 35 40
45 His Leu Pro Pro Leu Pro Ala Ala Pro Gly Pro Arg Arg Arg Arg Arg
50 55 60 Pro Arg Thr Pro Pro Ala Ala Pro Arg Ala Arg Pro Gly Glu
Arg Ala 65 70 75 80 Leu Leu Leu His Leu Pro Ala Phe Gly Arg Asp Leu
Tyr Leu Gln Leu 85 90 95 Arg Arg Asp Leu Arg Phe Leu Ser Arg Gly
Phe Glu Val Glu Glu Ala 100 105 110 Gly Ala Ala Arg Arg Arg Gly Arg
Pro Ala Glu Leu Cys Phe Tyr Ser 115 120 125 Gly Arg Val Leu Gly His
Pro Gly Ser Leu Val Ser Leu Ser Ala Cys 130 135 140 Gly Ala Ala Gly
Gly Leu Val Leu Pro Ala Pro Pro Pro Gly Arg Pro 145 150 155 160 Val
Arg Ser Val Ala Thr Gln Ser Gly Arg Arg Gly Gly Trp Gly Trp 165 170
175 Gly Ala Ser Ala Gly Ser Pro Ala Ser Arg Gly Thr Gly Gly Asn Pro
180 185 190 Leu Pro Phe His Leu Ser Pro Ser Pro Thr Pro Ala Phe Gly
Thr Leu 195 200 205 Tyr Arg Gln Arg Gly Trp Glu Gly Gln His Pro Ser
Pro Ala Pro Leu 210 215 220 Gln Pro Val Glu Pro Ala Arg Ser Trp Gly
Cys Val Gly Val Tyr Ala 225 230 235 240 Ala Arg Ser Arg Glu Arg Arg
Ser Gly Arg Asp Glu Thr Val Arg Ala 245 250 255 Leu Asp Arg Gly Ala
Leu Ala Pro Met 260 265 39 958 DNA Homo sapiens CDS (31)..(931) 39
gcagcacccg cagccagagc cgcgctcggc atg atg ccc ggg gcg ccg ctc 51 Met
Met Pro Gly Ala Pro Leu 1 5 ctg cgg ctg ctg acc gcg gtc tct gcg gca
gtg gca gtg gca gtg gcc 99 Leu Arg Leu Leu Thr Ala Val Ser Ala Ala
Val Ala Val Ala Val Ala 10 15 20 ggg gcg ccc ggg acg gta atg ccc
ccc acc acg ggg gac gcc acc ctg 147 Gly Ala Pro Gly Thr Val Met Pro
Pro Thr Thr Gly Asp Ala Thr Leu 25 30 35 gcc ttc gtc ttc gac gtc
acc ggc tcc atg tgg gac gaa ctg atg cag 195 Ala Phe Val Phe Asp Val
Thr Gly Ser Met Trp Asp Glu Leu Met Gln 40 45 50 55 gtg atc gat ggc
gcc tcg cgc att ctg gaa cgc agt ctg agc cgc cgc 243 Val Ile Asp Gly
Ala Ser Arg Ile Leu Glu Arg Ser Leu Ser Arg Arg 60 65 70 agc cag
gcc atc gcc aac tac gcg ctg gtg ccc ttc cac gac cca gat 291 Ser Gln
Ala Ile Ala Asn Tyr Ala Leu Val Pro Phe His Asp Pro Asp 75 80 85
att ggc cca gtg acc ctc acg gcg gac ccc aca gtg ttt cag agg gag 339
Ile Gly Pro Val Thr Leu Thr Ala Asp Pro Thr Val Phe Gln Arg Glu 90
95 100 ctg aga gaa ctc tac gtg cag gga ggt ggt gac tgc ccg gag atg
agt 387 Leu Arg Glu Leu Tyr Val Gln Gly Gly Gly Asp Cys Pro Glu Met
Ser 105 110 115 gtg ggg gcc att aag gct gcc gtg gag gtt gcc aac ccc
gga tcc ttc 435 Val Gly Ala Ile Lys Ala Ala Val Glu Val Ala Asn Pro
Gly Ser Phe 120 125 130 135 atc tac gtc ttt tcg gat gcc cgc gcc aaa
gac tat cac aag aag gaa 483 Ile Tyr Val Phe Ser Asp Ala Arg Ala Lys
Asp Tyr His Lys Lys Glu 140 145 150 gag ctg ctg cgg ctc ctg cag ctc
aag caa tca cag gtg gtc ttt gtg 531 Glu Leu Leu Arg Leu Leu Gln Leu
Lys Gln Ser Gln Val Val Phe Val 155 160 165 ctg acg ggg gac tgt ggc
gac cgc acc cat cct ggc tac ctg gct tat 579 Leu Thr Gly Asp Cys Gly
Asp Arg Thr His Pro Gly Tyr Leu Ala Tyr 170 175 180 gag gag atc gct
gcc acc agc tct ggg cag gtg ttc cac ctg gac aag 627 Glu Glu Ile Ala
Ala Thr Ser Ser Gly Gln Val Phe His Leu Asp Lys 185 190 195 cag caa
gtg aca gag gtg ctg aag tgg gtg gag tca gcg atc cag gcc 675 Gln Gln
Val Thr Glu Val Leu Lys Trp Val Glu Ser Ala Ile Gln Ala 200 205 210
215 tcc aag gtg cac ctg ctg tcc aca gac cac gag gag gag ggg gag cac
723 Ser Lys Val His Leu Leu Ser Thr Asp His Glu Glu Glu Gly Glu His
220 225 230 aca tgg aga ctc ccc ttt gac ccc agc ctg aag gag gtc acc
atc tca 771 Thr Trp Arg Leu Pro Phe Asp Pro Ser Leu Lys Glu Val Thr
Ile Ser 235 240 245 ttg agt ggg cca ggg cct gag att gaa gtc caa gat
ccg ctg ggt atg 819 Leu Ser Gly Pro Gly Pro Glu Ile Glu Val Gln Asp
Pro Leu Gly Met 250 255 260 gac cac ccc ggg gct ggc ctc ctc ttt ggc
ccc aag act gag gtg gaa 867 Asp His Pro Gly Ala Gly Leu Leu Phe Gly
Pro Lys Thr Glu Val Glu 265 270 275 gcc cag gat ggg aca aag aaa gag
acc aag ggt gac agg gct tca gac 915 Ala Gln Asp Gly Thr Lys Lys Glu
Thr Lys Gly Asp Arg Ala Ser Asp 280 285 290 295 atg agg ctc cag gaa
tagggaaata tggggtgggg gggacacg 958 Met Arg Leu Gln Glu 300 40 300
PRT Homo sapiens 40 Met Met Pro Gly Ala Pro Leu Leu Arg Leu Leu Thr
Ala Val Ser Ala 1 5 10 15 Ala Val Ala Val Ala Val Ala Gly Ala Pro
Gly Thr Val Met Pro Pro 20 25 30 Thr Thr Gly Asp Ala Thr Leu Ala
Phe Val Phe Asp Val Thr Gly Ser 35 40 45 Met Trp Asp Glu Leu Met
Gln Val Ile Asp Gly Ala Ser Arg Ile Leu 50 55 60 Glu Arg Ser Leu
Ser Arg Arg Ser Gln Ala Ile Ala Asn Tyr Ala Leu 65 70 75 80 Val Pro
Phe His Asp Pro Asp Ile Gly Pro Val Thr Leu Thr Ala Asp 85 90 95
Pro Thr Val Phe Gln Arg Glu Leu Arg Glu Leu Tyr Val Gln Gly Gly 100
105 110 Gly Asp Cys Pro Glu Met Ser Val Gly Ala Ile Lys Ala Ala Val
Glu 115 120 125 Val Ala Asn Pro Gly Ser Phe Ile Tyr Val Phe Ser Asp
Ala Arg Ala 130 135 140 Lys Asp Tyr His Lys Lys Glu Glu Leu Leu Arg
Leu Leu Gln Leu Lys 145 150 155 160 Gln Ser Gln Val Val Phe Val Leu
Thr Gly Asp Cys Gly Asp Arg Thr 165 170 175 His Pro Gly Tyr Leu Ala
Tyr Glu Glu Ile Ala Ala Thr Ser Ser Gly 180 185 190 Gln Val Phe His
Leu Asp Lys Gln Gln Val Thr Glu Val Leu Lys Trp 195 200 205 Val Glu
Ser Ala Ile Gln Ala Ser Lys Val His Leu Leu Ser Thr Asp 210 215 220
His Glu Glu Glu Gly Glu His Thr Trp Arg Leu Pro Phe Asp Pro Ser 225
230 235 240 Leu Lys Glu Val Thr Ile Ser Leu Ser Gly Pro Gly Pro Glu
Ile Glu 245 250 255 Val Gln Asp Pro Leu Gly Met Asp His Pro Gly Ala
Gly Leu Leu Phe 260 265 270 Gly Pro Lys Thr Glu Val Glu Ala Gln Asp
Gly Thr Lys Lys Glu Thr 275 280 285 Lys Gly Asp Arg Ala Ser Asp Met
Arg Leu Gln Glu 290 295 300 41 2916 DNA Homo sapiens CDS
(31)..(2914) 41 gcagcacccg cagccagagc cgcgctcggc atg atg ccc ggg
gcg ccg ctc 51 Met Met Pro Gly Ala Pro Leu 1 5 ctg cgg ctg ctg acc
gcg gtc tct gcg gca gtg gca gtg gca gtg gcc 99 Leu Arg Leu Leu Thr
Ala Val Ser Ala Ala Val Ala Val Ala Val Ala 10 15 20 ggg gcg ccc
ggg acg gta atg ccc ccc acc acg ggg gac gcc acc ctg 147 Gly Ala Pro
Gly Thr Val Met Pro Pro Thr Thr Gly Asp Ala Thr Leu 25 30 35 gcc
ttc gtc ttc gac gtc acc ggc tcc atg tgg gac gaa ctg atg cag 195 Ala
Phe Val Phe Asp Val Thr Gly Ser Met Trp Asp Glu Leu Met Gln 40 45
50 55 gtg atc gat ggc gcc tcg cgc att ctg gaa cgc agt ctg agc cgc
cgc 243 Val Ile Asp Gly Ala Ser Arg Ile Leu Glu Arg Ser Leu Ser Arg
Arg 60 65 70 agc cag gcc atc gcc aac tac gcg ctg gtg ccc ttc cac
gac cca gat 291 Ser Gln Ala Ile Ala Asn Tyr Ala Leu Val Pro Phe His
Asp Pro Asp 75 80 85 att ggc cca gtg acc ctc acg gcg gac ccc aca
gtg ttt cag agg gag 339 Ile Gly Pro Val Thr Leu Thr Ala Asp Pro Thr
Val Phe Gln Arg Glu 90 95 100 ctg aga gaa ctc tac gtg cag gga ggt
ggt gac tgc ccg gag atg agt 387 Leu Arg Glu Leu Tyr Val Gln Gly Gly
Gly Asp Cys Pro Glu Met Ser 105 110 115 gtg ggg gcc att aag gct gcc
gtg gag gtt gcc aac ccc gga tcc ttc 435 Val Gly Ala Ile Lys Ala Ala
Val Glu Val Ala Asn Pro Gly Ser Phe 120 125 130 135 atc tac gtc ttt
tcg gat gcc cgc gcc aaa gac tat cac aag aag gaa 483 Ile Tyr Val Phe
Ser Asp Ala Arg Ala Lys Asp Tyr His Lys Lys Glu 140 145 150 gag ctg
ctg cgg ctc ctg cag ctc aag caa tca cag gtg gtc ttt gtg 531 Glu Leu
Leu Arg Leu Leu Gln Leu Lys Gln Ser Gln Val Val Phe Val 155 160 165
ctg acg ggg gac tgt ggc gac cgc acc cat cct ggc tac ctg gct tat 579
Leu Thr Gly Asp Cys Gly Asp Arg Thr His Pro Gly Tyr Leu Ala Tyr 170
175 180 gag gag atc gct gcc acc agc tct ggg cag gtg ttc cac ctg gac
aag 627 Glu Glu Ile Ala Ala Thr Ser Ser Gly Gln Val Phe His Leu Asp
Lys 185 190 195 cag caa gtg aca gag gca ggt gct tcc gtg ttt cca ggc
aaa att gtg 675 Gln Gln Val Thr Glu Ala Gly Ala Ser Val Phe Pro Gly
Lys Ile Val 200 205 210 215 cag gag cac agg atc ctt tca ggg gcc agc
tgg gaa atg atg aac aac 723 Gln Glu His Arg Ile Leu Ser Gly Ala Ser
Trp Glu Met Met Asn Asn 220 225 230 gct ctc tct gga aag gac aag cac
acc cat ttc cgt ggt ata aat gct 771 Ala Leu Ser Gly Lys Asp Lys His
Thr His Phe Arg Gly Ile Asn Ala 235 240 245 ccc acc tcg gct gat tcc
aag tca gag ttg gga agt gac gct gac act 819 Pro Thr Ser Ala Asp Ser
Lys Ser Glu Leu Gly Ser Asp Ala Asp Thr 250 255 260 cag ctt tcc gga
gcc tac aca agt ggc tcc cac aca cca ctg gat ccc 867 Gln Leu Ser Gly
Ala Tyr Thr Ser Gly Ser His Thr Pro Leu Asp Pro 265 270 275 gca cag
gca cct ctc acc gcc agt tgg gtt aac gag agc ccc tac ctg 915 Ala Gln
Ala Pro Leu Thr Ala Ser Trp Val Asn Glu Ser Pro Tyr Leu 280 285 290
295 gtg ctg aag tgg gtg gag tca gcg atc cag gcc tcc aag gtg cac ctg
963 Val Leu Lys Trp Val Glu Ser Ala Ile Gln Ala Ser Lys Val His Leu
300 305 310 ctg tcc aca gac cac gag gag gag ggg gag cac aca tgg aga
ctc ccc 1011 Leu Ser Thr Asp His Glu Glu Glu Gly Glu His Thr Trp
Arg Leu Pro 315
320 325 ttt gac ccc agc ctg aag gag gtc acc atc tca ttg agt ggg cca
ggg 1059 Phe Asp Pro Ser Leu Lys Glu Val Thr Ile Ser Leu Ser Gly
Pro Gly 330 335 340 cct gag att gaa gtc caa gat ccg ctg ggt atg gac
cac ccc ggg gct 1107 Pro Glu Ile Glu Val Gln Asp Pro Leu Gly Met
Asp His Pro Gly Ala 345 350 355 ggc ctc ctc ttt ggc ccc aag act gag
gtg gaa gcc cag gat ggg aca 1155 Gly Leu Leu Phe Gly Pro Lys Thr
Glu Val Glu Ala Gln Asp Gly Thr 360 365 370 375 aag aaa gag acc aag
ggg agg atc ctg cag gag gac gag ggc ctc aac 1203 Lys Lys Glu Thr
Lys Gly Arg Ile Leu Gln Glu Asp Glu Gly Leu Asn 380 385 390 gtg ctt
ctc aac atc cct gac tcg gcc aag gtc gta gcc ttt aag cct 1251 Val
Leu Leu Asn Ile Pro Asp Ser Ala Lys Val Val Ala Phe Lys Pro 395 400
405 gag cat ccg ggg ctg tgg tcc atc aag gtc tat agc agt ggc cgc cat
1299 Glu His Pro Gly Leu Trp Ser Ile Lys Val Tyr Ser Ser Gly Arg
His 410 415 420 tca gtg agg atc aca ggc gtc agc aac att gac ttc cga
gcc ggc ttc 1347 Ser Val Arg Ile Thr Gly Val Ser Asn Ile Asp Phe
Arg Ala Gly Phe 425 430 435 tcc act cag ccc ttg ctg gac ctc aac cac
acc ctc gag tgg ccc ttg 1395 Ser Thr Gln Pro Leu Leu Asp Leu Asn
His Thr Leu Glu Trp Pro Leu 440 445 450 455 caa gga gtc ccc atc tcc
ctg gtg atc aat tcc acg ggc ctg aag gca 1443 Gln Gly Val Pro Ile
Ser Leu Val Ile Asn Ser Thr Gly Leu Lys Ala 460 465 470 ccc ggc cgc
cta gac tcg gtg gag ctg gca caa agc tca ggg aag ccc 1491 Pro Gly
Arg Leu Asp Ser Val Glu Leu Ala Gln Ser Ser Gly Lys Pro 475 480 485
ctc ctg act ctg ccc acg aag ccc ctc tcc aat ggc tcc acc cat cag
1539 Leu Leu Thr Leu Pro Thr Lys Pro Leu Ser Asn Gly Ser Thr His
Gln 490 495 500 ctg tgg ggc ggg ccg ccc ttc cac acc ccc aag gag cgc
ttc tac ctc 1587 Leu Trp Gly Gly Pro Pro Phe His Thr Pro Lys Glu
Arg Phe Tyr Leu 505 510 515 aag gtg aag ggc aag gac cat gag gga aac
ccc ctc ctt cgt gtc tct 1635 Lys Val Lys Gly Lys Asp His Glu Gly
Asn Pro Leu Leu Arg Val Ser 520 525 530 535 gga gtg tcc tac agt ggg
gtg gcc cca ggc gct ccc ctc gtc agc atg 1683 Gly Val Ser Tyr Ser
Gly Val Ala Pro Gly Ala Pro Leu Val Ser Met 540 545 550 gcc ccc agg
atc cat ggc tac ctg cac cag ccc ctg ctg gtc tcc tgc 1731 Ala Pro
Arg Ile His Gly Tyr Leu His Gln Pro Leu Leu Val Ser Cys 555 560 565
tcg gtg cac agt gcc ctt ccc ttc cgg ctg cag ctg cgg cga ggt gaa
1779 Ser Val His Ser Ala Leu Pro Phe Arg Leu Gln Leu Arg Arg Gly
Glu 570 575 580 gcc agg ctg ggc gaa gag agg cac ttt cag gag tcg gga
aac agc agc 1827 Ala Arg Leu Gly Glu Glu Arg His Phe Gln Glu Ser
Gly Asn Ser Ser 585 590 595 tgg gag atc ctg cgg gcc tcc aag gcc gag
gag ggc acg tac gag tgc 1875 Trp Glu Ile Leu Arg Ala Ser Lys Ala
Glu Glu Gly Thr Tyr Glu Cys 600 605 610 615 aca gcc gtc agc agg gct
ggg acc ggg cga gca aag gcc cag att gtt 1923 Thr Ala Val Ser Arg
Ala Gly Thr Gly Arg Ala Lys Ala Gln Ile Val 620 625 630 gtc acc ctg
cac ctc agg gtg ggg ttc ggg gca gca cca ggg ctt gca 1971 Val Thr
Leu His Leu Arg Val Gly Phe Gly Ala Ala Pro Gly Leu Ala 635 640 645
cga aga ccc cct ccc ttg cct cag ctc ctt ggt tcc tcc tgt gct cat
2019 Arg Arg Pro Pro Pro Leu Pro Gln Leu Leu Gly Ser Ser Cys Ala
His 650 655 660 gtc cct gca gac ccc ccg ccg cag ctg gtc cct gct ccc
aac gtg acc 2067 Val Pro Ala Asp Pro Pro Pro Gln Leu Val Pro Ala
Pro Asn Val Thr 665 670 675 gtg tcc cca ggg gag act gcc gtc cta tcc
tgc cgg gtc cta ggc gag 2115 Val Ser Pro Gly Glu Thr Ala Val Leu
Ser Cys Arg Val Leu Gly Glu 680 685 690 695 gcc ccc tac aac ctg acg
tgg gtc cgg gac tgg cga gtc ctg ccg gcc 2163 Ala Pro Tyr Asn Leu
Thr Trp Val Arg Asp Trp Arg Val Leu Pro Ala 700 705 710 tcg acg ggc
cga gtt gcc cag ctg gct gac ctg tcc ctg gag atc agt 2211 Ser Thr
Gly Arg Val Ala Gln Leu Ala Asp Leu Ser Leu Glu Ile Ser 715 720 725
ggc atc atc ccc aca gac ggc ggg agg tac cag tgt gtg gcc agc aat
2259 Gly Ile Ile Pro Thr Asp Gly Gly Arg Tyr Gln Cys Val Ala Ser
Asn 730 735 740 gcc aat ggg gtc aca agg gca tcc gtc tgg ctc ctg gtg
cga gag gcc 2307 Ala Asn Gly Val Thr Arg Ala Ser Val Trp Leu Leu
Val Arg Glu Ala 745 750 755 cca cag gtc agc atc cac acc agc tcc cag
cac ttc tcc caa ggt gtg 2355 Pro Gln Val Ser Ile His Thr Ser Ser
Gln His Phe Ser Gln Gly Val 760 765 770 775 gag gtg aag gtc agc tgc
tca gcc tct gga tac ccc aca ccc cac atc 2403 Glu Val Lys Val Ser
Cys Ser Ala Ser Gly Tyr Pro Thr Pro His Ile 780 785 790 tcc tgg agc
cgt gag agc caa gcc cta caa gag gac agc aga atc cat 2451 Ser Trp
Ser Arg Glu Ser Gln Ala Leu Gln Glu Asp Ser Arg Ile His 795 800 805
gtg gac gca cag gga acc ctg att att cag ggg gta gcc cca gag gat
2499 Val Asp Ala Gln Gly Thr Leu Ile Ile Gln Gly Val Ala Pro Glu
Asp 810 815 820 gct ggg aat tac agc tgc cag gcg act aat gag gtt ggc
act gac cag 2547 Ala Gly Asn Tyr Ser Cys Gln Ala Thr Asn Glu Val
Gly Thr Asp Gln 825 830 835 gag acg gtc acc ctc tac tac aca gac cca
ccg tcg gtc tct gct gta 2595 Glu Thr Val Thr Leu Tyr Tyr Thr Asp
Pro Pro Ser Val Ser Ala Val 840 845 850 855 aat gcc gtg gtg ctg gtg
gcc gtt ggg gag gag gct gtg ttg gtg tgt 2643 Asn Ala Val Val Leu
Val Ala Val Gly Glu Glu Ala Val Leu Val Cys 860 865 870 gag gca tct
ggg gtt ccc ccg ccc cga gtc atc tgg tat cga ggg ggt 2691 Glu Ala
Ser Gly Val Pro Pro Pro Arg Val Ile Trp Tyr Arg Gly Gly 875 880 885
ctt gaa atg atc ctg gcc cct gag ggc tcc agc tct ggg aag ctg cgg
2739 Leu Glu Met Ile Leu Ala Pro Glu Gly Ser Ser Ser Gly Lys Leu
Arg 890 895 900 atc ccg gcg gct cag gag agg gat gct ggc acc tac acc
tgc cgg gct 2787 Ile Pro Ala Ala Gln Glu Arg Asp Ala Gly Thr Tyr
Thr Cys Arg Ala 905 910 915 gtc aat gag ttg ggt gac gcc tct gca gaa
atc cag ctg gcg gtt gga 2835 Val Asn Glu Leu Gly Asp Ala Ser Ala
Glu Ile Gln Leu Ala Val Gly 920 925 930 935 cat gcg ccc cag ctg acg
gag ctg ccc cgg gat gtc act gtg gaa ctg 2883 His Ala Pro Gln Leu
Thr Glu Leu Pro Arg Asp Val Thr Val Glu Leu 940 945 950 ggg agg agt
gcc cag ctg cgg cgt ggg act taa 2916 Gly Arg Ser Ala Gln Leu Arg
Arg Gly Thr 955 960 42 961 PRT Homo sapiens 42 Met Met Pro Gly Ala
Pro Leu Leu Arg Leu Leu Thr Ala Val Ser Ala 1 5 10 15 Ala Val Ala
Val Ala Val Ala Gly Ala Pro Gly Thr Val Met Pro Pro 20 25 30 Thr
Thr Gly Asp Ala Thr Leu Ala Phe Val Phe Asp Val Thr Gly Ser 35 40
45 Met Trp Asp Glu Leu Met Gln Val Ile Asp Gly Ala Ser Arg Ile Leu
50 55 60 Glu Arg Ser Leu Ser Arg Arg Ser Gln Ala Ile Ala Asn Tyr
Ala Leu 65 70 75 80 Val Pro Phe His Asp Pro Asp Ile Gly Pro Val Thr
Leu Thr Ala Asp 85 90 95 Pro Thr Val Phe Gln Arg Glu Leu Arg Glu
Leu Tyr Val Gln Gly Gly 100 105 110 Gly Asp Cys Pro Glu Met Ser Val
Gly Ala Ile Lys Ala Ala Val Glu 115 120 125 Val Ala Asn Pro Gly Ser
Phe Ile Tyr Val Phe Ser Asp Ala Arg Ala 130 135 140 Lys Asp Tyr His
Lys Lys Glu Glu Leu Leu Arg Leu Leu Gln Leu Lys 145 150 155 160 Gln
Ser Gln Val Val Phe Val Leu Thr Gly Asp Cys Gly Asp Arg Thr 165 170
175 His Pro Gly Tyr Leu Ala Tyr Glu Glu Ile Ala Ala Thr Ser Ser Gly
180 185 190 Gln Val Phe His Leu Asp Lys Gln Gln Val Thr Glu Ala Gly
Ala Ser 195 200 205 Val Phe Pro Gly Lys Ile Val Gln Glu His Arg Ile
Leu Ser Gly Ala 210 215 220 Ser Trp Glu Met Met Asn Asn Ala Leu Ser
Gly Lys Asp Lys His Thr 225 230 235 240 His Phe Arg Gly Ile Asn Ala
Pro Thr Ser Ala Asp Ser Lys Ser Glu 245 250 255 Leu Gly Ser Asp Ala
Asp Thr Gln Leu Ser Gly Ala Tyr Thr Ser Gly 260 265 270 Ser His Thr
Pro Leu Asp Pro Ala Gln Ala Pro Leu Thr Ala Ser Trp 275 280 285 Val
Asn Glu Ser Pro Tyr Leu Val Leu Lys Trp Val Glu Ser Ala Ile 290 295
300 Gln Ala Ser Lys Val His Leu Leu Ser Thr Asp His Glu Glu Glu Gly
305 310 315 320 Glu His Thr Trp Arg Leu Pro Phe Asp Pro Ser Leu Lys
Glu Val Thr 325 330 335 Ile Ser Leu Ser Gly Pro Gly Pro Glu Ile Glu
Val Gln Asp Pro Leu 340 345 350 Gly Met Asp His Pro Gly Ala Gly Leu
Leu Phe Gly Pro Lys Thr Glu 355 360 365 Val Glu Ala Gln Asp Gly Thr
Lys Lys Glu Thr Lys Gly Arg Ile Leu 370 375 380 Gln Glu Asp Glu Gly
Leu Asn Val Leu Leu Asn Ile Pro Asp Ser Ala 385 390 395 400 Lys Val
Val Ala Phe Lys Pro Glu His Pro Gly Leu Trp Ser Ile Lys 405 410 415
Val Tyr Ser Ser Gly Arg His Ser Val Arg Ile Thr Gly Val Ser Asn 420
425 430 Ile Asp Phe Arg Ala Gly Phe Ser Thr Gln Pro Leu Leu Asp Leu
Asn 435 440 445 His Thr Leu Glu Trp Pro Leu Gln Gly Val Pro Ile Ser
Leu Val Ile 450 455 460 Asn Ser Thr Gly Leu Lys Ala Pro Gly Arg Leu
Asp Ser Val Glu Leu 465 470 475 480 Ala Gln Ser Ser Gly Lys Pro Leu
Leu Thr Leu Pro Thr Lys Pro Leu 485 490 495 Ser Asn Gly Ser Thr His
Gln Leu Trp Gly Gly Pro Pro Phe His Thr 500 505 510 Pro Lys Glu Arg
Phe Tyr Leu Lys Val Lys Gly Lys Asp His Glu Gly 515 520 525 Asn Pro
Leu Leu Arg Val Ser Gly Val Ser Tyr Ser Gly Val Ala Pro 530 535 540
Gly Ala Pro Leu Val Ser Met Ala Pro Arg Ile His Gly Tyr Leu His 545
550 555 560 Gln Pro Leu Leu Val Ser Cys Ser Val His Ser Ala Leu Pro
Phe Arg 565 570 575 Leu Gln Leu Arg Arg Gly Glu Ala Arg Leu Gly Glu
Glu Arg His Phe 580 585 590 Gln Glu Ser Gly Asn Ser Ser Trp Glu Ile
Leu Arg Ala Ser Lys Ala 595 600 605 Glu Glu Gly Thr Tyr Glu Cys Thr
Ala Val Ser Arg Ala Gly Thr Gly 610 615 620 Arg Ala Lys Ala Gln Ile
Val Val Thr Leu His Leu Arg Val Gly Phe 625 630 635 640 Gly Ala Ala
Pro Gly Leu Ala Arg Arg Pro Pro Pro Leu Pro Gln Leu 645 650 655 Leu
Gly Ser Ser Cys Ala His Val Pro Ala Asp Pro Pro Pro Gln Leu 660 665
670 Val Pro Ala Pro Asn Val Thr Val Ser Pro Gly Glu Thr Ala Val Leu
675 680 685 Ser Cys Arg Val Leu Gly Glu Ala Pro Tyr Asn Leu Thr Trp
Val Arg 690 695 700 Asp Trp Arg Val Leu Pro Ala Ser Thr Gly Arg Val
Ala Gln Leu Ala 705 710 715 720 Asp Leu Ser Leu Glu Ile Ser Gly Ile
Ile Pro Thr Asp Gly Gly Arg 725 730 735 Tyr Gln Cys Val Ala Ser Asn
Ala Asn Gly Val Thr Arg Ala Ser Val 740 745 750 Trp Leu Leu Val Arg
Glu Ala Pro Gln Val Ser Ile His Thr Ser Ser 755 760 765 Gln His Phe
Ser Gln Gly Val Glu Val Lys Val Ser Cys Ser Ala Ser 770 775 780 Gly
Tyr Pro Thr Pro His Ile Ser Trp Ser Arg Glu Ser Gln Ala Leu 785 790
795 800 Gln Glu Asp Ser Arg Ile His Val Asp Ala Gln Gly Thr Leu Ile
Ile 805 810 815 Gln Gly Val Ala Pro Glu Asp Ala Gly Asn Tyr Ser Cys
Gln Ala Thr 820 825 830 Asn Glu Val Gly Thr Asp Gln Glu Thr Val Thr
Leu Tyr Tyr Thr Asp 835 840 845 Pro Pro Ser Val Ser Ala Val Asn Ala
Val Val Leu Val Ala Val Gly 850 855 860 Glu Glu Ala Val Leu Val Cys
Glu Ala Ser Gly Val Pro Pro Pro Arg 865 870 875 880 Val Ile Trp Tyr
Arg Gly Gly Leu Glu Met Ile Leu Ala Pro Glu Gly 885 890 895 Ser Ser
Ser Gly Lys Leu Arg Ile Pro Ala Ala Gln Glu Arg Asp Ala 900 905 910
Gly Thr Tyr Thr Cys Arg Ala Val Asn Glu Leu Gly Asp Ala Ser Ala 915
920 925 Glu Ile Gln Leu Ala Val Gly His Ala Pro Gln Leu Thr Glu Leu
Pro 930 935 940 Arg Asp Val Thr Val Glu Leu Gly Arg Ser Ala Gln Leu
Arg Arg Gly 945 950 955 960 Thr 43 1023 DNA Homo sapiens CDS
(628)..(1023) 43 ctcgagtgtg gaactcactc ttaacgtacc tgaggagtgt
ccaacgtctt 50 tggacaaggc catactctca tgttcctttt cactcagctt
tacccacaca 100 gaaattttgg ggacccatgg gggactcagc agttgccaag
gtctgcagcc 150 tcctccaagg ggttcccatc tagttctcaa gaggaaggag
ggggttctca 200 gtcgccaggt gggcatggca ctcccgaggc caggtgagca
ggtcagtgcc 250 ttggggctca gggctgctcc ggttcttacc gaattgatcc
agtcgttgta 300 gttggagacc cgcgtgaaga tggagggctt gtagtagtag
ttgcaaccaa 350 ggaccgacgt gaggctgccg atgccatgca cctcccaccg
gccgtcagat 400 gcctgacagt tcagcggccc accggagtct ccgttgcagg
tgcatatcac 450 gccatcaccc ccagcacaga tcatattcgt cttcacggtg
ctgccccacc 500 agccagagtt ggagcaggtg gcatagtcca caaccagcaa
ccggccctgc 550 ttcaggtcat cagggagagc cccgttggtc tgcagccttc
cccagcccgt 600 gacgtagcag gggtagttgt tgggtag aat ggt gcc ggc agg
agg gag gca 651 Asn Gly Ala Gly Arg Arg Glu Ala 1 5 ggc cag ctg gat
ctt gtc ggt gag gga gac ggg gtt agc cag ttt gag 699 Gly Gln Leu Asp
Leu Val Gly Glu Gly Asp Gly Val Ser Gln Phe Glu 10 15 20 cag ggc
aat gtc gtt ccc ttt gga gac ctg gtc gga gtt cca gtc ctt 747 Gln Gly
Asn Val Val Pro Phe Gly Asp Leu Val Gly Val Pro Val Leu 25 30 35 40
gtg cac cac aat ctt aga gac act gac ggc cag cga gcc gga ctc tgc 795
Val His His Asn Leu Arg Asp Thr Asp Gly Gln Arg Ala Gly Leu Cys 45
50 55 aac gta gag gtt atg ctg gcc cag cat cac gcg gta gat ccc gga
gga 843 Asn Val Glu Val Met Leu Ala Gln His His Ala Val Asp Pro Gly
Gly 60 65 70 gct gat gca gtg ggc agc cgt cag gac cca gct gtt ggc
tat cag gga 891 Ala Asp Ala Val Gly Ser Arg Gln Asp Pro Ala Val Gly
Tyr Gln Gly 75 80 85 ccc tcc gca ggt gtg gta cca ctg gcc att gga
gct gta ctg cag gga 939 Pro Ser Ala Gly Val Val Pro Leu Ala Ile Gly
Ala Val Leu Gln Gly 90 95 100 gac ctg cca ggg ccg gct gtt ggg cct
cgc ttc ttc acc tcc aag cat 987 Asp Leu Pro Gly Pro Ala Val Gly Pro
Arg Phe Phe Thr Ser Lys His 105 110 115 120 cct aga cat atc agg cgc
gta agt gga gac gga tcc 1023 Pro Arg His Ile Arg Arg Val Ser Gly
Asp Gly Ser 125 130 44 132 PRT Homo sapiens 44 Asn Gly Ala Gly Arg
Arg Glu Ala Gly Gln Leu Asp Leu Val Gly Glu 1 5 10 15 Gly Asp Gly
Val Ser Gln Phe Glu Gln Gly Asn Val Val Pro Phe Gly 20 25 30 Asp
Leu Val Gly Val Pro Val Leu Val His His Asn Leu Arg Asp Thr 35 40
45 Asp Gly Gln Arg Ala Gly Leu Cys Asn Val Glu Val Met Leu Ala Gln
50 55 60 His His Ala Val Asp Pro Gly Gly Ala Asp Ala Val Gly Ser
Arg Gln 65 70 75 80 Asp Pro Ala Val Gly Tyr Gln Gly Pro Ser Ala Gly
Val Val Pro Leu 85 90 95 Ala Ile Gly Ala Val Leu Gln Gly Asp Leu
Pro Gly
Pro Ala Val Gly 100 105 110 Pro Arg Phe Phe Thr Ser Lys His Pro Arg
His Ile Arg Arg Val Ser 115 120 125 Gly Asp Gly Ser 130 45 2058 DNA
Homo sapiens CDS (1)..(2058) 45 aag ctt gtg gca gtg gcc ggg gcg ccc
ggg acg gta atg ccc ccc acc 48 Lys Leu Val Ala Val Ala Gly Ala Pro
Gly Thr Val Met Pro Pro Thr 1 5 10 15 acg ggg gac gcc acc ctg gcc
ttc gtc ttc gac gtc acc ggc tcc atg 96 Thr Gly Asp Ala Thr Leu Ala
Phe Val Phe Asp Val Thr Gly Ser Met 20 25 30 tgg gac gaa ctg atg
cag gtg atc gat ggc gcc tcg cgc att ctg gaa 144 Trp Asp Glu Leu Met
Gln Val Ile Asp Gly Ala Ser Arg Ile Leu Glu 35 40 45 cgc agt ctg
agc cgc cgc agc cag gcc atc gcc aac tac gcg ctg gtg 192 Arg Ser Leu
Ser Arg Arg Ser Gln Ala Ile Ala Asn Tyr Ala Leu Val 50 55 60 ccc
ttc cac gac cca gat att ggc cca gtg acc ctc acg gcg gac ccc 240 Pro
Phe His Asp Pro Asp Ile Gly Pro Val Thr Leu Thr Ala Asp Pro 65 70
75 80 aca gtg ttt cag agg gag ctg aga gaa ctc tac gtg cag gga ggt
ggt 288 Thr Val Phe Gln Arg Glu Leu Arg Glu Leu Tyr Val Gln Gly Gly
Gly 85 90 95 gac tgc ccg gag atg agt gtg ggg gcc att aag gct gcc
gtg gag gtt 336 Asp Cys Pro Glu Met Ser Val Gly Ala Ile Lys Ala Ala
Val Glu Val 100 105 110 gcc aac ccc gga tcc ttc atc tac gtc ttt tcg
gat gcc cgc gcc aaa 384 Ala Asn Pro Gly Ser Phe Ile Tyr Val Phe Ser
Asp Ala Arg Ala Lys 115 120 125 gac tat cac aag aag gaa gag ctg ctg
cgg ctc ctg cag ctc aag caa 432 Asp Tyr His Lys Lys Glu Glu Leu Leu
Arg Leu Leu Gln Leu Lys Gln 130 135 140 tca cag gtg gtc ttt gtg ctg
acg ggg gac tgt ggc gac cac acc cat 480 Ser Gln Val Val Phe Val Leu
Thr Gly Asp Cys Gly Asp His Thr His 145 150 155 160 cct ggc tac ctg
gct tat gag gag atc gct gcc acc agc tct ggg cag 528 Pro Gly Tyr Leu
Ala Tyr Glu Glu Ile Ala Ala Thr Ser Ser Gly Gln 165 170 175 gtg ttc
cac ctg gac aag cag caa gtg aca gag gtg ctg aag tgg gtg 576 Val Phe
His Leu Asp Lys Gln Gln Val Thr Glu Val Leu Lys Trp Val 180 185 190
gag tca gcg atc cag gcc tcc aag gtg cac ctg ctg tcc aca gac cac 624
Glu Ser Ala Ile Gln Ala Ser Lys Val His Leu Leu Ser Thr Asp His 195
200 205 gag gag gag ggg gag cac aca tgg aga ctc ccc ttt gac ccc agc
ctg 672 Glu Glu Glu Gly Glu His Thr Trp Arg Leu Pro Phe Asp Pro Ser
Leu 210 215 220 aag gag gtc acc atc tca ttg agt ggg cca ggg cct gag
att gaa gtc 720 Lys Glu Val Thr Ile Ser Leu Ser Gly Pro Gly Pro Glu
Ile Glu Val 225 230 235 240 caa gat ccg ctg ggg agg atc ctg cag gag
gac gag ggc ctc aac gtg 768 Gln Asp Pro Leu Gly Arg Ile Leu Gln Glu
Asp Glu Gly Leu Asn Val 245 250 255 ctt ctc aac atc cct gac tcg gcc
aag gtc gta gcc ttt aag cct gag 816 Leu Leu Asn Ile Pro Asp Ser Ala
Lys Val Val Ala Phe Lys Pro Glu 260 265 270 cat ccg ggg ctg tgg tcc
atc aag gtc tat agc agt ggc cgc cat tca 864 His Pro Gly Leu Trp Ser
Ile Lys Val Tyr Ser Ser Gly Arg His Ser 275 280 285 gtg agg atc aca
ggc gtc agc aac att gac ttc cga gcc ggc ttc tcc 912 Val Arg Ile Thr
Gly Val Ser Asn Ile Asp Phe Arg Ala Gly Phe Ser 290 295 300 act cag
ccc ttg ctg gac ctc aac cac acc ctc gag tgg ccc ttg caa 960 Thr Gln
Pro Leu Leu Asp Leu Asn His Thr Leu Glu Trp Pro Leu Gln 305 310 315
320 gga gtc ccc atc tcc ctg gtg atc aat tcc acg ggc ctg aag gca ccc
1008 Gly Val Pro Ile Ser Leu Val Ile Asn Ser Thr Gly Leu Lys Ala
Pro 325 330 335 ggc cgc cta gac tcg gtg gag ctg gca caa agc tca ggg
aag ccc ctc 1056 Gly Arg Leu Asp Ser Val Glu Leu Ala Gln Ser Ser
Gly Lys Pro Leu 340 345 350 ctg act ctg ccc acg aag ccc ctc tcc aat
ggc tcc acc cat cag ctg 1104 Leu Thr Leu Pro Thr Lys Pro Leu Ser
Asn Gly Ser Thr His Gln Leu 355 360 365 tgg ggc ggg cca ccc ttc cac
acc ccc aag gag cgc ttc tac ctc aag 1152 Trp Gly Gly Pro Pro Phe
His Thr Pro Lys Glu Arg Phe Tyr Leu Lys 370 375 380 gtg aag ggc aag
gac cat gag gga aac ccc ctc ctt cgt gtc tct gga 1200 Val Lys Gly
Lys Asp His Glu Gly Asn Pro Leu Leu Arg Val Ser Gly 385 390 395 400
gtg tcc tac agt ggg gtg gcc cca ggc gct ccc ctc gtc agc atg gtc
1248 Val Ser Tyr Ser Gly Val Ala Pro Gly Ala Pro Leu Val Ser Met
Val 405 410 415 ccc agg atc cat ggc tac ctg cac cag ccc ctg ctg gtc
tcc tgc tcg 1296 Pro Arg Ile His Gly Tyr Leu His Gln Pro Leu Leu
Val Ser Cys Ser 420 425 430 gtg cac agt gcc ctt ccc ttc cgg ctg cag
ctg cgg cga ggt gaa gcc 1344 Val His Ser Ala Leu Pro Phe Arg Leu
Gln Leu Arg Arg Gly Glu Ala 435 440 445 agg ctg ggc gaa gag agg cac
ttt cag gag tcg gga aac agt agc tgg 1392 Arg Leu Gly Glu Glu Arg
His Phe Gln Glu Ser Gly Asn Ser Ser Trp 450 455 460 gag atc ctg cgg
gcc tcc aag gcc gag gag ggc acg tac gag tgc aca 1440 Glu Ile Leu
Arg Ala Ser Lys Ala Glu Glu Gly Thr Tyr Glu Cys Thr 465 470 475 480
gcc gtc agc agg gct ggg acc ggg cga gca aag gcc cag att gtt gtc
1488 Ala Val Ser Arg Ala Gly Thr Gly Arg Ala Lys Ala Gln Ile Val
Val 485 490 495 aca gac ccc ccg ccg cag ctg gtc cct gct ccc aac gtg
acc gtg tcc 1536 Thr Asp Pro Pro Pro Gln Leu Val Pro Ala Pro Asn
Val Thr Val Ser 500 505 510 cca ggg gag act gcc gtc cta tcc tgc cgg
gtc cta ggc gag gcc ccc 1584 Pro Gly Glu Thr Ala Val Leu Ser Cys
Arg Val Leu Gly Glu Ala Pro 515 520 525 tac aac ctg acg tgg gtc cgg
gac tgg cga gtc ctg ccg gcc tcg acg 1632 Tyr Asn Leu Thr Trp Val
Arg Asp Trp Arg Val Leu Pro Ala Ser Thr 530 535 540 ggc cga gtt gcc
cag ctg gct gac ctg tcc ctg gag atc agt ggc atc 1680 Gly Arg Val
Ala Gln Leu Ala Asp Leu Ser Leu Glu Ile Ser Gly Ile 545 550 555 560
atc ccc aca gac ggc ggg agg tac cag tgt gtg gcc agc aat gcc aat
1728 Ile Pro Thr Asp Gly Gly Arg Tyr Gln Cys Val Ala Ser Asn Ala
Asn 565 570 575 ggg gtc aca agg gca tcc gtc tgg ctc ctg gtg cga gag
gtc cca cag 1776 Gly Val Thr Arg Ala Ser Val Trp Leu Leu Val Arg
Glu Val Pro Gln 580 585 590 gtc agc atc cac acc agc tcc cag cac ttc
tcc caa ggt gtg gag gtg 1824 Val Ser Ile His Thr Ser Ser Gln His
Phe Ser Gln Gly Val Glu Val 595 600 605 aag gtc agc tgc tca gcc tct
gga tac ccc aca ccc cac atc tcc tgg 1872 Lys Val Ser Cys Ser Ala
Ser Gly Tyr Pro Thr Pro His Ile Ser Trp 610 615 620 agc cgt gag agc
caa gcc cta caa gag gac agc aga atc cat gtg gac 1920 Ser Arg Glu
Ser Gln Ala Leu Gln Glu Asp Ser Arg Ile His Val Asp 625 630 635 640
gca cag gga acc ctg att att cag ggg gta gcc cca gag gat gct ggg
1968 Ala Gln Gly Thr Leu Ile Ile Gln Gly Val Ala Pro Glu Asp Ala
Gly 645 650 655 aat tac agc tgc cag gcg act aat gag gtt ggc act gac
cag gag acg 2016 Asn Tyr Ser Cys Gln Ala Thr Asn Glu Val Gly Thr
Asp Gln Glu Thr 660 665 670 gtc acc ctc tac tac aca gac cca ccg tcg
gtc tct gtc gac 2058 Val Thr Leu Tyr Tyr Thr Asp Pro Pro Ser Val
Ser Val Asp 675 680 685 46 686 PRT Homo sapiens 46 Lys Leu Val Ala
Val Ala Gly Ala Pro Gly Thr Val Met Pro Pro Thr 1 5 10 15 Thr Gly
Asp Ala Thr Leu Ala Phe Val Phe Asp Val Thr Gly Ser Met 20 25 30
Trp Asp Glu Leu Met Gln Val Ile Asp Gly Ala Ser Arg Ile Leu Glu 35
40 45 Arg Ser Leu Ser Arg Arg Ser Gln Ala Ile Ala Asn Tyr Ala Leu
Val 50 55 60 Pro Phe His Asp Pro Asp Ile Gly Pro Val Thr Leu Thr
Ala Asp Pro 65 70 75 80 Thr Val Phe Gln Arg Glu Leu Arg Glu Leu Tyr
Val Gln Gly Gly Gly 85 90 95 Asp Cys Pro Glu Met Ser Val Gly Ala
Ile Lys Ala Ala Val Glu Val 100 105 110 Ala Asn Pro Gly Ser Phe Ile
Tyr Val Phe Ser Asp Ala Arg Ala Lys 115 120 125 Asp Tyr His Lys Lys
Glu Glu Leu Leu Arg Leu Leu Gln Leu Lys Gln 130 135 140 Ser Gln Val
Val Phe Val Leu Thr Gly Asp Cys Gly Asp His Thr His 145 150 155 160
Pro Gly Tyr Leu Ala Tyr Glu Glu Ile Ala Ala Thr Ser Ser Gly Gln 165
170 175 Val Phe His Leu Asp Lys Gln Gln Val Thr Glu Val Leu Lys Trp
Val 180 185 190 Glu Ser Ala Ile Gln Ala Ser Lys Val His Leu Leu Ser
Thr Asp His 195 200 205 Glu Glu Glu Gly Glu His Thr Trp Arg Leu Pro
Phe Asp Pro Ser Leu 210 215 220 Lys Glu Val Thr Ile Ser Leu Ser Gly
Pro Gly Pro Glu Ile Glu Val 225 230 235 240 Gln Asp Pro Leu Gly Arg
Ile Leu Gln Glu Asp Glu Gly Leu Asn Val 245 250 255 Leu Leu Asn Ile
Pro Asp Ser Ala Lys Val Val Ala Phe Lys Pro Glu 260 265 270 His Pro
Gly Leu Trp Ser Ile Lys Val Tyr Ser Ser Gly Arg His Ser 275 280 285
Val Arg Ile Thr Gly Val Ser Asn Ile Asp Phe Arg Ala Gly Phe Ser 290
295 300 Thr Gln Pro Leu Leu Asp Leu Asn His Thr Leu Glu Trp Pro Leu
Gln 305 310 315 320 Gly Val Pro Ile Ser Leu Val Ile Asn Ser Thr Gly
Leu Lys Ala Pro 325 330 335 Gly Arg Leu Asp Ser Val Glu Leu Ala Gln
Ser Ser Gly Lys Pro Leu 340 345 350 Leu Thr Leu Pro Thr Lys Pro Leu
Ser Asn Gly Ser Thr His Gln Leu 355 360 365 Trp Gly Gly Pro Pro Phe
His Thr Pro Lys Glu Arg Phe Tyr Leu Lys 370 375 380 Val Lys Gly Lys
Asp His Glu Gly Asn Pro Leu Leu Arg Val Ser Gly 385 390 395 400 Val
Ser Tyr Ser Gly Val Ala Pro Gly Ala Pro Leu Val Ser Met Val 405 410
415 Pro Arg Ile His Gly Tyr Leu His Gln Pro Leu Leu Val Ser Cys Ser
420 425 430 Val His Ser Ala Leu Pro Phe Arg Leu Gln Leu Arg Arg Gly
Glu Ala 435 440 445 Arg Leu Gly Glu Glu Arg His Phe Gln Glu Ser Gly
Asn Ser Ser Trp 450 455 460 Glu Ile Leu Arg Ala Ser Lys Ala Glu Glu
Gly Thr Tyr Glu Cys Thr 465 470 475 480 Ala Val Ser Arg Ala Gly Thr
Gly Arg Ala Lys Ala Gln Ile Val Val 485 490 495 Thr Asp Pro Pro Pro
Gln Leu Val Pro Ala Pro Asn Val Thr Val Ser 500 505 510 Pro Gly Glu
Thr Ala Val Leu Ser Cys Arg Val Leu Gly Glu Ala Pro 515 520 525 Tyr
Asn Leu Thr Trp Val Arg Asp Trp Arg Val Leu Pro Ala Ser Thr 530 535
540 Gly Arg Val Ala Gln Leu Ala Asp Leu Ser Leu Glu Ile Ser Gly Ile
545 550 555 560 Ile Pro Thr Asp Gly Gly Arg Tyr Gln Cys Val Ala Ser
Asn Ala Asn 565 570 575 Gly Val Thr Arg Ala Ser Val Trp Leu Leu Val
Arg Glu Val Pro Gln 580 585 590 Val Ser Ile His Thr Ser Ser Gln His
Phe Ser Gln Gly Val Glu Val 595 600 605 Lys Val Ser Cys Ser Ala Ser
Gly Tyr Pro Thr Pro His Ile Ser Trp 610 615 620 Ser Arg Glu Ser Gln
Ala Leu Gln Glu Asp Ser Arg Ile His Val Asp 625 630 635 640 Ala Gln
Gly Thr Leu Ile Ile Gln Gly Val Ala Pro Glu Asp Ala Gly 645 650 655
Asn Tyr Ser Cys Gln Ala Thr Asn Glu Val Gly Thr Asp Gln Glu Thr 660
665 670 Val Thr Leu Tyr Tyr Thr Asp Pro Pro Ser Val Ser Val Asp 675
680 685 47 2058 DNA Homo sapiens CDS (1)..(2058) 47 aag ctt gtg gca
gtg gcc ggg gcg ccc ggg acg gta atg ccc ccc acc 48 Lys Leu Val Ala
Val Ala Gly Ala Pro Gly Thr Val Met Pro Pro Thr 1 5 10 15 acg ggg
gac gcc acc ctg gcc ttc gtc ttc gac gtc acc ggc tcc atg 96 Thr Gly
Asp Ala Thr Leu Ala Phe Val Phe Asp Val Thr Gly Ser Met 20 25 30
tgg gac gaa ctg atg cag gtg atc gat ggc gcc tcg cgc att ctg gaa 144
Trp Asp Glu Leu Met Gln Val Ile Asp Gly Ala Ser Arg Ile Leu Glu 35
40 45 cgc agt ctg agc cgc cgc agc cag gcc atc gcc aac tac gcg ctg
gtg 192 Arg Ser Leu Ser Arg Arg Ser Gln Ala Ile Ala Asn Tyr Ala Leu
Val 50 55 60 ccc ttc cac gac cca gat att ggc cca gtg acc ctc acg
gcg gac ccc 240 Pro Phe His Asp Pro Asp Ile Gly Pro Val Thr Leu Thr
Ala Asp Pro 65 70 75 80 aca gtg ttt cag agg gag ctg aga gaa ctc tac
gtg cag gga ggt ggt 288 Thr Val Phe Gln Arg Glu Leu Arg Glu Leu Tyr
Val Gln Gly Gly Gly 85 90 95 gac tgc ccg gag atg agt gtg ggg gcc
att aag gct gcc gtg gag gtt 336 Asp Cys Pro Glu Met Ser Val Gly Ala
Ile Lys Ala Ala Val Glu Val 100 105 110 gcc aac ccc gga tcc ttc atc
tac gtc ttt tcg gat gcc cgc gcc aaa 384 Ala Asn Pro Gly Ser Phe Ile
Tyr Val Phe Ser Asp Ala Arg Ala Lys 115 120 125 gac tat cac aag aag
gaa gag ctg ctg cgg ctc ctg cag ctc aag caa 432 Asp Tyr His Lys Lys
Glu Glu Leu Leu Arg Leu Leu Gln Leu Lys Gln 130 135 140 tca cag gtg
gtc ttt gtg ctg acg ggg gac tgt ggc gac cac acc cat 480 Ser Gln Val
Val Phe Val Leu Thr Gly Asp Cys Gly Asp His Thr His 145 150 155 160
cct ggc tac ctg gct tat gag gag atc gct gcc acc agc tct ggg cag 528
Pro Gly Tyr Leu Ala Tyr Glu Glu Ile Ala Ala Thr Ser Ser Gly Gln 165
170 175 gtg ttc cac ctg gac aag cag caa gtg aca gag gtg ctg aag tgg
gtg 576 Val Phe His Leu Asp Lys Gln Gln Val Thr Glu Val Leu Lys Trp
Val 180 185 190 gag tca gcg atc cag gcc tcc aag gtg cac ctg ctg tcc
aca gac cac 624 Glu Ser Ala Ile Gln Ala Ser Lys Val His Leu Leu Ser
Thr Asp His 195 200 205 gag gag gag ggg gag cac aca tgg aga ctc ccc
ttt gac ccc agc ctg 672 Glu Glu Glu Gly Glu His Thr Trp Arg Leu Pro
Phe Asp Pro Ser Leu 210 215 220 aag gag gtc acc atc tca ttg agt ggg
cca ggg cct gag att gaa gtc 720 Lys Glu Val Thr Ile Ser Leu Ser Gly
Pro Gly Pro Glu Ile Glu Val 225 230 235 240 caa gat ccg ctg ggg agg
atc ctg cag gag gac gag ggc ctc aac gtg 768 Gln Asp Pro Leu Gly Arg
Ile Leu Gln Glu Asp Glu Gly Leu Asn Val 245 250 255 ctt ctc aac atc
cct gac tcg gcc aag gtc gta gcc ttt aag cct gag 816 Leu Leu Asn Ile
Pro Asp Ser Ala Lys Val Val Ala Phe Lys Pro Glu 260 265 270 cat ccg
ggg ctg tgg tcc atc aag gtc tat agc agt ggc cgc cat tca 864 His Pro
Gly Leu Trp Ser Ile Lys Val Tyr Ser Ser Gly Arg His Ser 275 280 285
gtg agg atc aca ggc gtc agc aac att gac ttc cga gcc ggc ttc tcc 912
Val Arg Ile Thr Gly Val Ser Asn Ile Asp Phe Arg Ala Gly Phe Ser 290
295 300 act cag ccc ttg ctg gac ctc aac cac acc ctc gag tgg ccc ttg
caa 960 Thr Gln Pro Leu Leu Asp Leu Asn His Thr Leu Glu Trp Pro Leu
Gln 305 310 315 320 gga gtc ccc atc tcc ctg gtg atc aat tcc acg ggc
ctg aag gca ccc 1008 Gly Val Pro Ile Ser Leu Val Ile Asn Ser Thr
Gly Leu Lys Ala Pro 325 330 335 ggc cgc cta gac tcg gtg gag ctg gca
caa agc tca ggg aag ccc ctc 1056 Gly Arg Leu Asp Ser Val Glu Leu
Ala Gln Ser Ser Gly Lys Pro Leu 340 345 350 ctg act ctg ccc acg aag
ccc ctc tcc aat ggc tcc acc cat cag ctg 1104 Leu Thr Leu Pro Thr
Lys Pro Leu Ser Asn Gly Ser Thr His Gln Leu 355 360 365 tgg ggc ggg
ccg ccc ttc cac acc ccc aag gag cgc ttc tac ctc aag 1152 Trp Gly
Gly Pro Pro Phe His Thr Pro Lys Glu Arg Phe Tyr Leu
Lys 370 375 380 gtg aag ggc aag gac cat gag gga aac ccc ctc ctt cgt
gtc tct gga 1200 Val Lys Gly Lys Asp His Glu Gly Asn Pro Leu Leu
Arg Val Ser Gly 385 390 395 400 gtg tcc tac agt ggg gtg gcc cca ggc
gct ccc ctc gtc agc atg gcc 1248 Val Ser Tyr Ser Gly Val Ala Pro
Gly Ala Pro Leu Val Ser Met Ala 405 410 415 ccc agg atc cat ggc tac
ctg cac cag ccc ctg ctg gtc tcc tgc tcg 1296 Pro Arg Ile His Gly
Tyr Leu His Gln Pro Leu Leu Val Ser Cys Ser 420 425 430 gtg cac agt
gcc ctt ccc ttc cgg ctg cag ctg cgg cga ggt gaa gcc 1344 Val His
Ser Ala Leu Pro Phe Arg Leu Gln Leu Arg Arg Gly Glu Ala 435 440 445
agg ctg ggc gaa gag agg cac ttt cag gag tcg gga aac agc agc tgg
1392 Arg Leu Gly Glu Glu Arg His Phe Gln Glu Ser Gly Asn Ser Ser
Trp 450 455 460 gag atc ctg cgg gcc tcc aag gcc gag gag ggc acg tac
gag tgc aca 1440 Glu Ile Leu Arg Ala Ser Lys Ala Glu Glu Gly Thr
Tyr Glu Cys Thr 465 470 475 480 gcc gtc agc agg gct ggg acc ggg cga
gca aag gcc cag att gtt gtc 1488 Ala Val Ser Arg Ala Gly Thr Gly
Arg Ala Lys Ala Gln Ile Val Val 485 490 495 aca gac ccc ccg ccg cag
ctg gtc cct gct ccc aac gtg acc gtg tcc 1536 Thr Asp Pro Pro Pro
Gln Leu Val Pro Ala Pro Asn Val Thr Val Ser 500 505 510 cca ggg gag
act gcc gtc cta tcc tgc cgg gtc cta ggc gag gcc ccc 1584 Pro Gly
Glu Thr Ala Val Leu Ser Cys Arg Val Leu Gly Glu Ala Pro 515 520 525
tac aac ctg acg tgg gtc cgg gac tgg cga gtc ctg ccg gcc tcg acg
1632 Tyr Asn Leu Thr Trp Val Arg Asp Trp Arg Val Leu Pro Ala Ser
Thr 530 535 540 ggc cga gtt gcc cag ctg gct gac ctg tcc ctg gag atc
agt ggc atc 1680 Gly Arg Val Ala Gln Leu Ala Asp Leu Ser Leu Glu
Ile Ser Gly Ile 545 550 555 560 atc ccc aca gac ggc ggg agg tac cag
tgt gtg gcc agc aat gcc aat 1728 Ile Pro Thr Asp Gly Gly Arg Tyr
Gln Cys Val Ala Ser Asn Ala Asn 565 570 575 ggg gtc aca agg gca tcc
gtc tgg ctc ctg gtg cga gag gcc cca cag 1776 Gly Val Thr Arg Ala
Ser Val Trp Leu Leu Val Arg Glu Ala Pro Gln 580 585 590 gtc agc atc
cac acc agc tcc cag cac ttc tcc caa ggt gtg gag gtg 1824 Val Ser
Ile His Thr Ser Ser Gln His Phe Ser Gln Gly Val Glu Val 595 600 605
aag gtc agc tgc tca gcc tct gga tac ccc aca ccc cac atc tcc tgg
1872 Lys Val Ser Cys Ser Ala Ser Gly Tyr Pro Thr Pro His Ile Ser
Trp 610 615 620 agc cgt gag agc caa gcc cta caa gag gac agc aga atc
cat gtg gac 1920 Ser Arg Glu Ser Gln Ala Leu Gln Glu Asp Ser Arg
Ile His Val Asp 625 630 635 640 gca cag gga acc ctg att att cag ggg
gta gcc cca gag gat gct ggg 1968 Ala Gln Gly Thr Leu Ile Ile Gln
Gly Val Ala Pro Glu Asp Ala Gly 645 650 655 aat tac agc tgc cag gcg
act aat gag gtt ggc act gac cag gag acg 2016 Asn Tyr Ser Cys Gln
Ala Thr Asn Glu Val Gly Thr Asp Gln Glu Thr 660 665 670 gtc acc ctc
tac gac aca gac cca ccg tcg gtc tct gtc gac 2058 Val Thr Leu Tyr
Asp Thr Asp Pro Pro Ser Val Ser Val Asp 675 680 685 48 686 PRT Homo
sapiens 48 Lys Leu Val Ala Val Ala Gly Ala Pro Gly Thr Val Met Pro
Pro Thr 1 5 10 15 Thr Gly Asp Ala Thr Leu Ala Phe Val Phe Asp Val
Thr Gly Ser Met 20 25 30 Trp Asp Glu Leu Met Gln Val Ile Asp Gly
Ala Ser Arg Ile Leu Glu 35 40 45 Arg Ser Leu Ser Arg Arg Ser Gln
Ala Ile Ala Asn Tyr Ala Leu Val 50 55 60 Pro Phe His Asp Pro Asp
Ile Gly Pro Val Thr Leu Thr Ala Asp Pro 65 70 75 80 Thr Val Phe Gln
Arg Glu Leu Arg Glu Leu Tyr Val Gln Gly Gly Gly 85 90 95 Asp Cys
Pro Glu Met Ser Val Gly Ala Ile Lys Ala Ala Val Glu Val 100 105 110
Ala Asn Pro Gly Ser Phe Ile Tyr Val Phe Ser Asp Ala Arg Ala Lys 115
120 125 Asp Tyr His Lys Lys Glu Glu Leu Leu Arg Leu Leu Gln Leu Lys
Gln 130 135 140 Ser Gln Val Val Phe Val Leu Thr Gly Asp Cys Gly Asp
His Thr His 145 150 155 160 Pro Gly Tyr Leu Ala Tyr Glu Glu Ile Ala
Ala Thr Ser Ser Gly Gln 165 170 175 Val Phe His Leu Asp Lys Gln Gln
Val Thr Glu Val Leu Lys Trp Val 180 185 190 Glu Ser Ala Ile Gln Ala
Ser Lys Val His Leu Leu Ser Thr Asp His 195 200 205 Glu Glu Glu Gly
Glu His Thr Trp Arg Leu Pro Phe Asp Pro Ser Leu 210 215 220 Lys Glu
Val Thr Ile Ser Leu Ser Gly Pro Gly Pro Glu Ile Glu Val 225 230 235
240 Gln Asp Pro Leu Gly Arg Ile Leu Gln Glu Asp Glu Gly Leu Asn Val
245 250 255 Leu Leu Asn Ile Pro Asp Ser Ala Lys Val Val Ala Phe Lys
Pro Glu 260 265 270 His Pro Gly Leu Trp Ser Ile Lys Val Tyr Ser Ser
Gly Arg His Ser 275 280 285 Val Arg Ile Thr Gly Val Ser Asn Ile Asp
Phe Arg Ala Gly Phe Ser 290 295 300 Thr Gln Pro Leu Leu Asp Leu Asn
His Thr Leu Glu Trp Pro Leu Gln 305 310 315 320 Gly Val Pro Ile Ser
Leu Val Ile Asn Ser Thr Gly Leu Lys Ala Pro 325 330 335 Gly Arg Leu
Asp Ser Val Glu Leu Ala Gln Ser Ser Gly Lys Pro Leu 340 345 350 Leu
Thr Leu Pro Thr Lys Pro Leu Ser Asn Gly Ser Thr His Gln Leu 355 360
365 Trp Gly Gly Pro Pro Phe His Thr Pro Lys Glu Arg Phe Tyr Leu Lys
370 375 380 Val Lys Gly Lys Asp His Glu Gly Asn Pro Leu Leu Arg Val
Ser Gly 385 390 395 400 Val Ser Tyr Ser Gly Val Ala Pro Gly Ala Pro
Leu Val Ser Met Ala 405 410 415 Pro Arg Ile His Gly Tyr Leu His Gln
Pro Leu Leu Val Ser Cys Ser 420 425 430 Val His Ser Ala Leu Pro Phe
Arg Leu Gln Leu Arg Arg Gly Glu Ala 435 440 445 Arg Leu Gly Glu Glu
Arg His Phe Gln Glu Ser Gly Asn Ser Ser Trp 450 455 460 Glu Ile Leu
Arg Ala Ser Lys Ala Glu Glu Gly Thr Tyr Glu Cys Thr 465 470 475 480
Ala Val Ser Arg Ala Gly Thr Gly Arg Ala Lys Ala Gln Ile Val Val 485
490 495 Thr Asp Pro Pro Pro Gln Leu Val Pro Ala Pro Asn Val Thr Val
Ser 500 505 510 Pro Gly Glu Thr Ala Val Leu Ser Cys Arg Val Leu Gly
Glu Ala Pro 515 520 525 Tyr Asn Leu Thr Trp Val Arg Asp Trp Arg Val
Leu Pro Ala Ser Thr 530 535 540 Gly Arg Val Ala Gln Leu Ala Asp Leu
Ser Leu Glu Ile Ser Gly Ile 545 550 555 560 Ile Pro Thr Asp Gly Gly
Arg Tyr Gln Cys Val Ala Ser Asn Ala Asn 565 570 575 Gly Val Thr Arg
Ala Ser Val Trp Leu Leu Val Arg Glu Ala Pro Gln 580 585 590 Val Ser
Ile His Thr Ser Ser Gln His Phe Ser Gln Gly Val Glu Val 595 600 605
Lys Val Ser Cys Ser Ala Ser Gly Tyr Pro Thr Pro His Ile Ser Trp 610
615 620 Ser Arg Glu Ser Gln Ala Leu Gln Glu Asp Ser Arg Ile His Val
Asp 625 630 635 640 Ala Gln Gly Thr Leu Ile Ile Gln Gly Val Ala Pro
Glu Asp Ala Gly 645 650 655 Asn Tyr Ser Cys Gln Ala Thr Asn Glu Val
Gly Thr Asp Gln Glu Thr 660 665 670 Val Thr Leu Tyr Asp Thr Asp Pro
Pro Ser Val Ser Val Asp 675 680 685 49 2058 DNA Homo sapiens CDS
(1)..(2058) 49 aag ctt gtg gca gtg gcc ggg gcg ccc ggg acg gta atg
ccc ccc acc 48 Lys Leu Val Ala Val Ala Gly Ala Pro Gly Thr Val Met
Pro Pro Thr 1 5 10 15 acg ggg gac gcc acc ctg gcc ttc gtc ttc gac
gtc acc ggc tcc atg 96 Thr Gly Asp Ala Thr Leu Ala Phe Val Phe Asp
Val Thr Gly Ser Met 20 25 30 tgg gac gaa ctg atg cag gtg atc gat
ggc gcc tcg cgc att ctg gaa 144 Trp Asp Glu Leu Met Gln Val Ile Asp
Gly Ala Ser Arg Ile Leu Glu 35 40 45 cgc agt ctg agc cgc cgc agc
cag gcc atc gcc aac tac gcg ctg gtg 192 Arg Ser Leu Ser Arg Arg Ser
Gln Ala Ile Ala Asn Tyr Ala Leu Val 50 55 60 ccc ttc cac gac cca
gat att ggc cca gtg acc ctc acg gcg gac ccc 240 Pro Phe His Asp Pro
Asp Ile Gly Pro Val Thr Leu Thr Ala Asp Pro 65 70 75 80 aca gtg ttt
cag agg gag ctg aga gaa ctc tac gtg cag gga ggt ggt 288 Thr Val Phe
Gln Arg Glu Leu Arg Glu Leu Tyr Val Gln Gly Gly Gly 85 90 95 gac
tgc ccg gag atg agt gtg ggg gcc att aag gct gcc gtg gag gtt 336 Asp
Cys Pro Glu Met Ser Val Gly Ala Ile Lys Ala Ala Val Glu Val 100 105
110 gcc aac ccc gga tcc ttc atc tac gtc ttt tcg gat gcc cgc gcc aaa
384 Ala Asn Pro Gly Ser Phe Ile Tyr Val Phe Ser Asp Ala Arg Ala Lys
115 120 125 gac tat cac aag aag gaa gag ctg ctg cgg ctc ctg cag ctc
aag caa 432 Asp Tyr His Lys Lys Glu Glu Leu Leu Arg Leu Leu Gln Leu
Lys Gln 130 135 140 tca cag gtg gtc ttt gtg ctg acg ggg gac tgt ggc
gac cac acc cat 480 Ser Gln Val Val Phe Val Leu Thr Gly Asp Cys Gly
Asp His Thr His 145 150 155 160 cct ggc tac ctg gct tat gag gag atc
gct gcc acc agc tct ggg cag 528 Pro Gly Tyr Leu Ala Tyr Glu Glu Ile
Ala Ala Thr Ser Ser Gly Gln 165 170 175 gtg ttc cac ctg gac aag cag
caa gtg aca gag gtg ctg aag tgg gtg 576 Val Phe His Leu Asp Lys Gln
Gln Val Thr Glu Val Leu Lys Trp Val 180 185 190 gag tca gcg atc cag
gcc tcc aag gtg cac ctg ctg tcc aca gac cac 624 Glu Ser Ala Ile Gln
Ala Ser Lys Val His Leu Leu Ser Thr Asp His 195 200 205 gag gag gag
ggg gag cac aca tgg aga ctc ccc ttt gac ccc agc ctg 672 Glu Glu Glu
Gly Glu His Thr Trp Arg Leu Pro Phe Asp Pro Ser Leu 210 215 220 aag
gag gtc acc atc tca ttg agt ggg cca ggg cct gag att gaa gtc 720 Lys
Glu Val Thr Ile Ser Leu Ser Gly Pro Gly Pro Glu Ile Glu Val 225 230
235 240 caa gat ccg ctg ggg agg atc ctg cag gag gac gag ggc ctc aac
gtg 768 Gln Asp Pro Leu Gly Arg Ile Leu Gln Glu Asp Glu Gly Leu Asn
Val 245 250 255 ctt ctc aac atc cct gac tcg gcc aag gtc gta gcc ttt
aag cct gag 816 Leu Leu Asn Ile Pro Asp Ser Ala Lys Val Val Ala Phe
Lys Pro Glu 260 265 270 cat ccg ggg ctg tgg tcc atc aag gtc tat agc
agt ggc cgc cat tca 864 His Pro Gly Leu Trp Ser Ile Lys Val Tyr Ser
Ser Gly Arg His Ser 275 280 285 gtg agg atc aca ggc gtc agc aac att
gac ttc cga gcc ggc ttc tcc 912 Val Arg Ile Thr Gly Val Ser Asn Ile
Asp Phe Arg Ala Gly Phe Ser 290 295 300 act cag ccc ttg ctg gac ctc
aac cac acc ctc gag tgg ccc ttg caa 960 Thr Gln Pro Leu Leu Asp Leu
Asn His Thr Leu Glu Trp Pro Leu Gln 305 310 315 320 gga gtc ccc atc
tcc ctg gtg atc aat tcc acg ggc ctg aag gca ccc 1008 Gly Val Pro
Ile Ser Leu Val Ile Asn Ser Thr Gly Leu Lys Ala Pro 325 330 335 ggc
cgc cta gac tcg gtg gag ctg gca caa agc tca ggg aag ccc ctc 1056
Gly Arg Leu Asp Ser Val Glu Leu Ala Gln Ser Ser Gly Lys Pro Leu 340
345 350 ctg act ctg ccc acg aag ccc ctc tcc aat ggc tcc acc cat cag
ctg 1104 Leu Thr Leu Pro Thr Lys Pro Leu Ser Asn Gly Ser Thr His
Gln Leu 355 360 365 tgg ggc ggg ccg ccc ttc cac acc ccc aag gag cgc
ttc tac ctc aag 1152 Trp Gly Gly Pro Pro Phe His Thr Pro Lys Glu
Arg Phe Tyr Leu Lys 370 375 380 gtg aag ggc aag gac cat gag gga aac
ccc ctc ctt cgt gtc tct gga 1200 Val Lys Gly Lys Asp His Glu Gly
Asn Pro Leu Leu Arg Val Ser Gly 385 390 395 400 gtg tcc tac agt ggg
gtg gcc cca ggc gct ccc ctc gtc agc atg gcc 1248 Val Ser Tyr Ser
Gly Val Ala Pro Gly Ala Pro Leu Val Ser Met Ala 405 410 415 ccc agg
atc cat ggc tac ctg cac cag ccc ctg ctg gtc tcc tgc tcg 1296 Pro
Arg Ile His Gly Tyr Leu His Gln Pro Leu Leu Val Ser Cys Ser 420 425
430 gtg cac agt gcc ctt ccc ttc cgg ctg cag ctg cgg cga ggt gaa gcc
1344 Val His Ser Ala Leu Pro Phe Arg Leu Gln Leu Arg Arg Gly Glu
Ala 435 440 445 agg ctg ggc gaa gag agg cac ttt cag gag tcg gga aac
agc agc tgg 1392 Arg Leu Gly Glu Glu Arg His Phe Gln Glu Ser Gly
Asn Ser Ser Trp 450 455 460 gag atc ctg cgg gcc tcc aag gcc gag gag
ggc acg tac gag tgc aca 1440 Glu Ile Leu Arg Ala Ser Lys Ala Glu
Glu Gly Thr Tyr Glu Cys Thr 465 470 475 480 gcc gtc agc agg gct ggg
acc ggg cga gca aag gcc cag att gtt gtc 1488 Ala Val Ser Arg Ala
Gly Thr Gly Arg Ala Lys Ala Gln Ile Val Val 485 490 495 aca gac ccc
ccg ccg cag ctg gtc cct gct ccc aac gtg acc gtg tcc 1536 Thr Asp
Pro Pro Pro Gln Leu Val Pro Ala Pro Asn Val Thr Val Ser 500 505 510
cca ggg gag gct gcc gtc cta tcc tgc cgg gtc cta ggc gag gcc ccc
1584 Pro Gly Glu Ala Ala Val Leu Ser Cys Arg Val Leu Gly Glu Ala
Pro 515 520 525 tac aac ctg acg tgg gtc cgg gac tgg cga gtc ctg ccg
gcc tcg acg 1632 Tyr Asn Leu Thr Trp Val Arg Asp Trp Arg Val Leu
Pro Ala Ser Thr 530 535 540 ggc cga gtt gcc cag ctg gct gac ctg tcc
ctg gag atc agt ggc atc 1680 Gly Arg Val Ala Gln Leu Ala Asp Leu
Ser Leu Glu Ile Ser Gly Ile 545 550 555 560 atc ccc aca gac ggc ggg
agg tac cag tgt gtg gcc agc aat gcc aat 1728 Ile Pro Thr Asp Gly
Gly Arg Tyr Gln Cys Val Ala Ser Asn Ala Asn 565 570 575 ggg gtc aca
agg gca tcc gtc tgg ctc ctg gtg cga gag gcc cca cag 1776 Gly Val
Thr Arg Ala Ser Val Trp Leu Leu Val Arg Glu Ala Pro Gln 580 585 590
gtc agc atc cac acc agc tcc cag cac ttc tcc caa ggt gtg gag gtg
1824 Val Ser Ile His Thr Ser Ser Gln His Phe Ser Gln Gly Val Glu
Val 595 600 605 aag gtc agc tgc tca gcc tct gga tac ccc aca ccc cac
atc tcc tgg 1872 Lys Val Ser Cys Ser Ala Ser Gly Tyr Pro Thr Pro
His Ile Ser Trp 610 615 620 agc cgt gag agc caa gcc cta caa gag gac
agc aga atc cat gtg gac 1920 Ser Arg Glu Ser Gln Ala Leu Gln Glu
Asp Ser Arg Ile His Val Asp 625 630 635 640 gca cag gga acc ctg att
att cag ggg gta gcc cca gag gat gct ggg 1968 Ala Gln Gly Thr Leu
Ile Ile Gln Gly Val Ala Pro Glu Asp Ala Gly 645 650 655 aat tac agc
tgc cag gcg act aat gag gtt ggc act gac cag gag acg 2016 Asn Tyr
Ser Cys Gln Ala Thr Asn Glu Val Gly Thr Asp Gln Glu Thr 660 665 670
gtc acc ctc tac tac aca gac cca ccg tcg gtc tct gtc gac 2058 Val
Thr Leu Tyr Tyr Thr Asp Pro Pro Ser Val Ser Val Asp 675 680 685 50
686 PRT Homo sapiens 50 Lys Leu Val Ala Val Ala Gly Ala Pro Gly Thr
Val Met Pro Pro Thr 1 5 10 15 Thr Gly Asp Ala Thr Leu Ala Phe Val
Phe Asp Val Thr Gly Ser Met 20 25 30 Trp Asp Glu Leu Met Gln Val
Ile Asp Gly Ala Ser Arg Ile Leu Glu 35 40 45 Arg Ser Leu Ser Arg
Arg Ser Gln Ala Ile Ala Asn Tyr Ala Leu Val 50 55 60 Pro Phe His
Asp Pro Asp Ile Gly Pro Val Thr Leu Thr Ala Asp Pro 65 70 75 80 Thr
Val Phe Gln Arg Glu Leu Arg Glu Leu Tyr Val Gln Gly Gly Gly 85 90
95 Asp Cys Pro Glu Met Ser Val Gly Ala Ile Lys Ala Ala Val Glu Val
100 105 110 Ala Asn Pro Gly Ser Phe Ile Tyr Val Phe Ser Asp Ala Arg
Ala Lys 115 120 125 Asp Tyr His Lys Lys Glu Glu Leu Leu Arg Leu Leu
Gln Leu Lys Gln 130 135 140 Ser Gln
Val Val Phe Val Leu Thr Gly Asp Cys Gly Asp His Thr His 145 150 155
160 Pro Gly Tyr Leu Ala Tyr Glu Glu Ile Ala Ala Thr Ser Ser Gly Gln
165 170 175 Val Phe His Leu Asp Lys Gln Gln Val Thr Glu Val Leu Lys
Trp Val 180 185 190 Glu Ser Ala Ile Gln Ala Ser Lys Val His Leu Leu
Ser Thr Asp His 195 200 205 Glu Glu Glu Gly Glu His Thr Trp Arg Leu
Pro Phe Asp Pro Ser Leu 210 215 220 Lys Glu Val Thr Ile Ser Leu Ser
Gly Pro Gly Pro Glu Ile Glu Val 225 230 235 240 Gln Asp Pro Leu Gly
Arg Ile Leu Gln Glu Asp Glu Gly Leu Asn Val 245 250 255 Leu Leu Asn
Ile Pro Asp Ser Ala Lys Val Val Ala Phe Lys Pro Glu 260 265 270 His
Pro Gly Leu Trp Ser Ile Lys Val Tyr Ser Ser Gly Arg His Ser 275 280
285 Val Arg Ile Thr Gly Val Ser Asn Ile Asp Phe Arg Ala Gly Phe Ser
290 295 300 Thr Gln Pro Leu Leu Asp Leu Asn His Thr Leu Glu Trp Pro
Leu Gln 305 310 315 320 Gly Val Pro Ile Ser Leu Val Ile Asn Ser Thr
Gly Leu Lys Ala Pro 325 330 335 Gly Arg Leu Asp Ser Val Glu Leu Ala
Gln Ser Ser Gly Lys Pro Leu 340 345 350 Leu Thr Leu Pro Thr Lys Pro
Leu Ser Asn Gly Ser Thr His Gln Leu 355 360 365 Trp Gly Gly Pro Pro
Phe His Thr Pro Lys Glu Arg Phe Tyr Leu Lys 370 375 380 Val Lys Gly
Lys Asp His Glu Gly Asn Pro Leu Leu Arg Val Ser Gly 385 390 395 400
Val Ser Tyr Ser Gly Val Ala Pro Gly Ala Pro Leu Val Ser Met Ala 405
410 415 Pro Arg Ile His Gly Tyr Leu His Gln Pro Leu Leu Val Ser Cys
Ser 420 425 430 Val His Ser Ala Leu Pro Phe Arg Leu Gln Leu Arg Arg
Gly Glu Ala 435 440 445 Arg Leu Gly Glu Glu Arg His Phe Gln Glu Ser
Gly Asn Ser Ser Trp 450 455 460 Glu Ile Leu Arg Ala Ser Lys Ala Glu
Glu Gly Thr Tyr Glu Cys Thr 465 470 475 480 Ala Val Ser Arg Ala Gly
Thr Gly Arg Ala Lys Ala Gln Ile Val Val 485 490 495 Thr Asp Pro Pro
Pro Gln Leu Val Pro Ala Pro Asn Val Thr Val Ser 500 505 510 Pro Gly
Glu Ala Ala Val Leu Ser Cys Arg Val Leu Gly Glu Ala Pro 515 520 525
Tyr Asn Leu Thr Trp Val Arg Asp Trp Arg Val Leu Pro Ala Ser Thr 530
535 540 Gly Arg Val Ala Gln Leu Ala Asp Leu Ser Leu Glu Ile Ser Gly
Ile 545 550 555 560 Ile Pro Thr Asp Gly Gly Arg Tyr Gln Cys Val Ala
Ser Asn Ala Asn 565 570 575 Gly Val Thr Arg Ala Ser Val Trp Leu Leu
Val Arg Glu Ala Pro Gln 580 585 590 Val Ser Ile His Thr Ser Ser Gln
His Phe Ser Gln Gly Val Glu Val 595 600 605 Lys Val Ser Cys Ser Ala
Ser Gly Tyr Pro Thr Pro His Ile Ser Trp 610 615 620 Ser Arg Glu Ser
Gln Ala Leu Gln Glu Asp Ser Arg Ile His Val Asp 625 630 635 640 Ala
Gln Gly Thr Leu Ile Ile Gln Gly Val Ala Pro Glu Asp Ala Gly 645 650
655 Asn Tyr Ser Cys Gln Ala Thr Asn Glu Val Gly Thr Asp Gln Glu Thr
660 665 670 Val Thr Leu Tyr Tyr Thr Asp Pro Pro Ser Val Ser Val Asp
675 680 685 51 2058 DNA Homo sapiens CDS (1)..(2058) 51 aag ctt gtg
gca gtg gcc ggg gcg ccc ggg acg gta atg ccc ccc acc 48 Lys Leu Val
Ala Val Ala Gly Ala Pro Gly Thr Val Met Pro Pro Thr 1 5 10 15 acg
ggg gac gcc acc ctg gcc ttc gtc ttc gac gtc acc ggc tcc atg 96 Thr
Gly Asp Ala Thr Leu Ala Phe Val Phe Asp Val Thr Gly Ser Met 20 25
30 tgg gac gaa ctg atg cag gtg atc gat ggc gcc tcg cgc att ctg gaa
144 Trp Asp Glu Leu Met Gln Val Ile Asp Gly Ala Ser Arg Ile Leu Glu
35 40 45 cgc agt ctg agc cgc cgc agc cag gcc atc gcc aac tac gcg
ctg gtg 192 Arg Ser Leu Ser Arg Arg Ser Gln Ala Ile Ala Asn Tyr Ala
Leu Val 50 55 60 ccc ttc cac gac cca gat att ggc cca gtg acc ctc
acg gcg gac ccc 240 Pro Phe His Asp Pro Asp Ile Gly Pro Val Thr Leu
Thr Ala Asp Pro 65 70 75 80 aca gtg ttt cag agg gag ctg aga gaa ctc
tac gtg cag gga ggt ggt 288 Thr Val Phe Gln Arg Glu Leu Arg Glu Leu
Tyr Val Gln Gly Gly Gly 85 90 95 gac tgc ccg gag atg agt gtg ggg
gcc att aag gct gcc gtg gag gtt 336 Asp Cys Pro Glu Met Ser Val Gly
Ala Ile Lys Ala Ala Val Glu Val 100 105 110 gcc aac ccc gga tcc ttc
atc tac gtc ttt tcg gat gcc cgc gcc aaa 384 Ala Asn Pro Gly Ser Phe
Ile Tyr Val Phe Ser Asp Ala Arg Ala Lys 115 120 125 gac tat cac aag
aag gaa gag ctg ctg cgg ctc ctg cag ctc aag caa 432 Asp Tyr His Lys
Lys Glu Glu Leu Leu Arg Leu Leu Gln Leu Lys Gln 130 135 140 tca cag
gtg gtc ttt gtg ctg acg ggg gac tgt ggc gac cac acc cat 480 Ser Gln
Val Val Phe Val Leu Thr Gly Asp Cys Gly Asp His Thr His 145 150 155
160 cct ggc tac ctg gct tat gag gag atc gct gcc acc agc tct ggg cag
528 Pro Gly Tyr Leu Ala Tyr Glu Glu Ile Ala Ala Thr Ser Ser Gly Gln
165 170 175 gtg ttc cac ctg gac aag cag caa gtg aca gag gtg ctg aag
tgg gtg 576 Val Phe His Leu Asp Lys Gln Gln Val Thr Glu Val Leu Lys
Trp Val 180 185 190 gag tca gcg atc cag gcc tcc aag gtg cac ctg ctg
tcc aca gac cac 624 Glu Ser Ala Ile Gln Ala Ser Lys Val His Leu Leu
Ser Thr Asp His 195 200 205 gag gag gag ggg gag cac aca tgg aga ctc
ccc ttt gac ccc agc ctg 672 Glu Glu Glu Gly Glu His Thr Trp Arg Leu
Pro Phe Asp Pro Ser Leu 210 215 220 aag gag gtc acc atc tca ttg agt
ggg cca ggg cct gag att gaa gtc 720 Lys Glu Val Thr Ile Ser Leu Ser
Gly Pro Gly Pro Glu Ile Glu Val 225 230 235 240 caa gat ccg ctg ggg
agg atc ctg cag gag gac gag ggc ctc aac gtg 768 Gln Asp Pro Leu Gly
Arg Ile Leu Gln Glu Asp Glu Gly Leu Asn Val 245 250 255 ctt ctc aac
atc cct gac tcg gcc aag gtc gta gcc ttt aag cct gag 816 Leu Leu Asn
Ile Pro Asp Ser Ala Lys Val Val Ala Phe Lys Pro Glu 260 265 270 cat
ccg ggg ctg tgg tcc atc aag gtc tat agc agt ggc cgc cat tca 864 His
Pro Gly Leu Trp Ser Ile Lys Val Tyr Ser Ser Gly Arg His Ser 275 280
285 gtg agg atc aca ggc gtc agc aac att gac ttc cga gcc ggc ttc tcc
912 Val Arg Ile Thr Gly Val Ser Asn Ile Asp Phe Arg Ala Gly Phe Ser
290 295 300 act cag ccc ttg ctg gac ctc aac cac acc ctc gag tgg ccc
ttg caa 960 Thr Gln Pro Leu Leu Asp Leu Asn His Thr Leu Glu Trp Pro
Leu Gln 305 310 315 320 gga gtc ccc atc tcc ctg gtg atc aat tcc acg
ggc ctg aag gca ccc 1008 Gly Val Pro Ile Ser Leu Val Ile Asn Ser
Thr Gly Leu Lys Ala Pro 325 330 335 ggc cgc cta gac tcg gtg gag ctg
gca caa agc tca ggg aag ccc ctc 1056 Gly Arg Leu Asp Ser Val Glu
Leu Ala Gln Ser Ser Gly Lys Pro Leu 340 345 350 ctg act ctg ccc acg
aag ccc ctc tcc aat ggc tcc acc cat cag ctg 1104 Leu Thr Leu Pro
Thr Lys Pro Leu Ser Asn Gly Ser Thr His Gln Leu 355 360 365 tgg ggc
ggg ccg ccc ttc cac acc ccc aag gag cgc ttc tac ctc aag 1152 Trp
Gly Gly Pro Pro Phe His Thr Pro Lys Glu Arg Phe Tyr Leu Lys 370 375
380 gtg aag ggc aag gac cat gag gga aac ccc ctc ctt cgt gtc tct gga
1200 Val Lys Gly Lys Asp His Glu Gly Asn Pro Leu Leu Arg Val Ser
Gly 385 390 395 400 gtg tcc tac agt ggg gtg gcc cca ggc gct ccc ctc
gtc agc atg gcc 1248 Val Ser Tyr Ser Gly Val Ala Pro Gly Ala Pro
Leu Val Ser Met Ala 405 410 415 ccc agg atc cat ggc tac ctg cac cag
ccc ctg ctg gtc tcc tgc tcg 1296 Pro Arg Ile His Gly Tyr Leu His
Gln Pro Leu Leu Val Ser Cys Ser 420 425 430 gtg cac agt gcc ctt ccc
ttc cgg ctg cag ctg cgg cga ggt gaa gcc 1344 Val His Ser Ala Leu
Pro Phe Arg Leu Gln Leu Arg Arg Gly Glu Ala 435 440 445 agg ctg ggc
gaa gag agg cac ttt cag gag tcg gga aac agc agc tgg 1392 Arg Leu
Gly Glu Glu Arg His Phe Gln Glu Ser Gly Asn Ser Ser Trp 450 455 460
gag atc ctg cgg gcc tcc aag gcc gag gag ggc acg tac gag tgc aca
1440 Glu Ile Leu Arg Ala Ser Lys Ala Glu Glu Gly Thr Tyr Glu Cys
Thr 465 470 475 480 gcc gtc agc agg gct ggg acc ggg cga gca aag gcc
cag att gtt gtc 1488 Ala Val Ser Arg Ala Gly Thr Gly Arg Ala Lys
Ala Gln Ile Val Val 485 490 495 aca gac ccc ccg ccg cag ctg gtc cct
gct ccc aac gtg acc gtg tcc 1536 Thr Asp Pro Pro Pro Gln Leu Val
Pro Ala Pro Asn Val Thr Val Ser 500 505 510 cca ggg gag act gcc gtc
cta tcc tgc cgg gtc cta ggc gag gcc ccc 1584 Pro Gly Glu Thr Ala
Val Leu Ser Cys Arg Val Leu Gly Glu Ala Pro 515 520 525 tac aac ctg
acg tgg gtc cgg gac tgg cga gtc ctg ccg gcc tcg acg 1632 Tyr Asn
Leu Thr Trp Val Arg Asp Trp Arg Val Leu Pro Ala Ser Thr 530 535 540
ggc cga gtt gcc cag ctg gct gac ctg tcc ctg gag atc agt ggc atc
1680 Gly Arg Val Ala Gln Leu Ala Asp Leu Ser Leu Glu Ile Ser Gly
Ile 545 550 555 560 atc ccc aca gac ggc ggg agg tac cag tgt gtg gcc
agc aat gcc aat 1728 Ile Pro Thr Asp Gly Gly Arg Tyr Gln Cys Val
Ala Ser Asn Ala Asn 565 570 575 ggg gtc aca agg aca tcc gtc tgg ctc
ctg gtg cga gag gcc cca cag 1776 Gly Val Thr Arg Thr Ser Val Trp
Leu Leu Val Arg Glu Ala Pro Gln 580 585 590 gtc agc atc cac acc agc
tcc cag cac ttc tcc caa ggt gtg gag gtg 1824 Val Ser Ile His Thr
Ser Ser Gln His Phe Ser Gln Gly Val Glu Val 595 600 605 aag gtc agc
tgc tca gcc tct gga tac ccc aca ccc cac atc tcc tgg 1872 Lys Val
Ser Cys Ser Ala Ser Gly Tyr Pro Thr Pro His Ile Ser Trp 610 615 620
agc cgt gag agc caa gcc cta caa gag gac agc aga atc cat gtg gac
1920 Ser Arg Glu Ser Gln Ala Leu Gln Glu Asp Ser Arg Ile His Val
Asp 625 630 635 640 gca cag gga acc ctg att att cag ggg gta gcc cca
gag gat gct ggg 1968 Ala Gln Gly Thr Leu Ile Ile Gln Gly Val Ala
Pro Glu Asp Ala Gly 645 650 655 aat tac agc tgc cag gcg act aat gag
gtt ggc act gac cag gag acg 2016 Asn Tyr Ser Cys Gln Ala Thr Asn
Glu Val Gly Thr Asp Gln Glu Thr 660 665 670 gtc acc ctc tac tac aca
gac cca ccg tcg gtc tct gtc gac 2058 Val Thr Leu Tyr Tyr Thr Asp
Pro Pro Ser Val Ser Val Asp 675 680 685 52 686 PRT Homo sapiens 52
Lys Leu Val Ala Val Ala Gly Ala Pro Gly Thr Val Met Pro Pro Thr 1 5
10 15 Thr Gly Asp Ala Thr Leu Ala Phe Val Phe Asp Val Thr Gly Ser
Met 20 25 30 Trp Asp Glu Leu Met Gln Val Ile Asp Gly Ala Ser Arg
Ile Leu Glu 35 40 45 Arg Ser Leu Ser Arg Arg Ser Gln Ala Ile Ala
Asn Tyr Ala Leu Val 50 55 60 Pro Phe His Asp Pro Asp Ile Gly Pro
Val Thr Leu Thr Ala Asp Pro 65 70 75 80 Thr Val Phe Gln Arg Glu Leu
Arg Glu Leu Tyr Val Gln Gly Gly Gly 85 90 95 Asp Cys Pro Glu Met
Ser Val Gly Ala Ile Lys Ala Ala Val Glu Val 100 105 110 Ala Asn Pro
Gly Ser Phe Ile Tyr Val Phe Ser Asp Ala Arg Ala Lys 115 120 125 Asp
Tyr His Lys Lys Glu Glu Leu Leu Arg Leu Leu Gln Leu Lys Gln 130 135
140 Ser Gln Val Val Phe Val Leu Thr Gly Asp Cys Gly Asp His Thr His
145 150 155 160 Pro Gly Tyr Leu Ala Tyr Glu Glu Ile Ala Ala Thr Ser
Ser Gly Gln 165 170 175 Val Phe His Leu Asp Lys Gln Gln Val Thr Glu
Val Leu Lys Trp Val 180 185 190 Glu Ser Ala Ile Gln Ala Ser Lys Val
His Leu Leu Ser Thr Asp His 195 200 205 Glu Glu Glu Gly Glu His Thr
Trp Arg Leu Pro Phe Asp Pro Ser Leu 210 215 220 Lys Glu Val Thr Ile
Ser Leu Ser Gly Pro Gly Pro Glu Ile Glu Val 225 230 235 240 Gln Asp
Pro Leu Gly Arg Ile Leu Gln Glu Asp Glu Gly Leu Asn Val 245 250 255
Leu Leu Asn Ile Pro Asp Ser Ala Lys Val Val Ala Phe Lys Pro Glu 260
265 270 His Pro Gly Leu Trp Ser Ile Lys Val Tyr Ser Ser Gly Arg His
Ser 275 280 285 Val Arg Ile Thr Gly Val Ser Asn Ile Asp Phe Arg Ala
Gly Phe Ser 290 295 300 Thr Gln Pro Leu Leu Asp Leu Asn His Thr Leu
Glu Trp Pro Leu Gln 305 310 315 320 Gly Val Pro Ile Ser Leu Val Ile
Asn Ser Thr Gly Leu Lys Ala Pro 325 330 335 Gly Arg Leu Asp Ser Val
Glu Leu Ala Gln Ser Ser Gly Lys Pro Leu 340 345 350 Leu Thr Leu Pro
Thr Lys Pro Leu Ser Asn Gly Ser Thr His Gln Leu 355 360 365 Trp Gly
Gly Pro Pro Phe His Thr Pro Lys Glu Arg Phe Tyr Leu Lys 370 375 380
Val Lys Gly Lys Asp His Glu Gly Asn Pro Leu Leu Arg Val Ser Gly 385
390 395 400 Val Ser Tyr Ser Gly Val Ala Pro Gly Ala Pro Leu Val Ser
Met Ala 405 410 415 Pro Arg Ile His Gly Tyr Leu His Gln Pro Leu Leu
Val Ser Cys Ser 420 425 430 Val His Ser Ala Leu Pro Phe Arg Leu Gln
Leu Arg Arg Gly Glu Ala 435 440 445 Arg Leu Gly Glu Glu Arg His Phe
Gln Glu Ser Gly Asn Ser Ser Trp 450 455 460 Glu Ile Leu Arg Ala Ser
Lys Ala Glu Glu Gly Thr Tyr Glu Cys Thr 465 470 475 480 Ala Val Ser
Arg Ala Gly Thr Gly Arg Ala Lys Ala Gln Ile Val Val 485 490 495 Thr
Asp Pro Pro Pro Gln Leu Val Pro Ala Pro Asn Val Thr Val Ser 500 505
510 Pro Gly Glu Thr Ala Val Leu Ser Cys Arg Val Leu Gly Glu Ala Pro
515 520 525 Tyr Asn Leu Thr Trp Val Arg Asp Trp Arg Val Leu Pro Ala
Ser Thr 530 535 540 Gly Arg Val Ala Gln Leu Ala Asp Leu Ser Leu Glu
Ile Ser Gly Ile 545 550 555 560 Ile Pro Thr Asp Gly Gly Arg Tyr Gln
Cys Val Ala Ser Asn Ala Asn 565 570 575 Gly Val Thr Arg Thr Ser Val
Trp Leu Leu Val Arg Glu Ala Pro Gln 580 585 590 Val Ser Ile His Thr
Ser Ser Gln His Phe Ser Gln Gly Val Glu Val 595 600 605 Lys Val Ser
Cys Ser Ala Ser Gly Tyr Pro Thr Pro His Ile Ser Trp 610 615 620 Ser
Arg Glu Ser Gln Ala Leu Gln Glu Asp Ser Arg Ile His Val Asp 625 630
635 640 Ala Gln Gly Thr Leu Ile Ile Gln Gly Val Ala Pro Glu Asp Ala
Gly 645 650 655 Asn Tyr Ser Cys Gln Ala Thr Asn Glu Val Gly Thr Asp
Gln Glu Thr 660 665 670 Val Thr Leu Tyr Tyr Thr Asp Pro Pro Ser Val
Ser Val Asp 675 680 685 53 621 DNA Homo sapiens CDS (4)..(598) 53
atc atg ccc cta ggt ctc ctg tgg ctg ggc cta gcc ctg ttg ggg gct 48
Met Pro Leu Gly Leu Leu Trp Leu Gly Leu Ala Leu Leu Gly Ala 1 5 10
15 ctg cat gcc cag gcc cag gac tcc acc tca gac ctg atc cca gcc cca
96 Leu His Ala Gln Ala Gln Asp Ser Thr Ser Asp Leu Ile Pro Ala Pro
20 25 30 cct ctg agc aag gtc cct ctg cag cag aac ttc cag gac aac
caa ttc 144 Pro Leu Ser Lys Val Pro Leu Gln Gln Asn Phe Gln Asp Asn
Gln Phe 35 40 45 cag ggg aag tgg tat gtg gta ggc ctg gca ggg aat
gca att ctc aga 192 Gln Gly Lys Trp Tyr Val Val Gly Leu Ala
Gly Asn Ala Ile Leu Arg 50 55 60 gaa gac aaa gac ccg caa aag atg
tat gcc acc atc tat gag ctg aaa 240 Glu Asp Lys Asp Pro Gln Lys Met
Tyr Ala Thr Ile Tyr Glu Leu Lys 65 70 75 gaa gac aag agc tac aat
gtc acc tcc gtc ctg ttt agg aaa aag aag 288 Glu Asp Lys Ser Tyr Asn
Val Thr Ser Val Leu Phe Arg Lys Lys Lys 80 85 90 95 tgt gac tac tgg
atc agg act ttt gtt cca ggt tgc cag ccc ggc gag 336 Cys Asp Tyr Trp
Ile Arg Thr Phe Val Pro Gly Cys Gln Pro Gly Glu 100 105 110 ttc acg
ctg ggc aac att aag agt tac cct gga tta acg agt tac ctc 384 Phe Thr
Leu Gly Asn Ile Lys Ser Tyr Pro Gly Leu Thr Ser Tyr Leu 115 120 125
gtc cga gtg gtg agc acc aac tac aac cag cat gct atg gtg ttc ttc 432
Val Arg Val Val Ser Thr Asn Tyr Asn Gln His Ala Met Val Phe Phe 130
135 140 aag aaa gtt tct caa aac agg gag tac ttc aag atc acc ctc tac
ggt 480 Lys Lys Val Ser Gln Asn Arg Glu Tyr Phe Lys Ile Thr Leu Tyr
Gly 145 150 155 aga acc aag gag ctg act tcg gaa cta aag gag aac ttc
atc cgc ttc 528 Arg Thr Lys Glu Leu Thr Ser Glu Leu Lys Glu Asn Phe
Ile Arg Phe 160 165 170 175 tcc aaa tct ctg ggc ctc cct gaa aac cac
atc gtc ttc cct gtc cca 576 Ser Lys Ser Leu Gly Leu Pro Glu Asn His
Ile Val Phe Pro Val Pro 180 185 190 atc ggt aat ggc cag tct gga
tgaggggacg gggacatggg gact 621 Ile Gly Asn Gly Gln Ser Gly 195 54
198 PRT Homo sapiens 54 Met Pro Leu Gly Leu Leu Trp Leu Gly Leu Ala
Leu Leu Gly Ala Leu 1 5 10 15 His Ala Gln Ala Gln Asp Ser Thr Ser
Asp Leu Ile Pro Ala Pro Pro 20 25 30 Leu Ser Lys Val Pro Leu Gln
Gln Asn Phe Gln Asp Asn Gln Phe Gln 35 40 45 Gly Lys Trp Tyr Val
Val Gly Leu Ala Gly Asn Ala Ile Leu Arg Glu 50 55 60 Asp Lys Asp
Pro Gln Lys Met Tyr Ala Thr Ile Tyr Glu Leu Lys Glu 65 70 75 80 Asp
Lys Ser Tyr Asn Val Thr Ser Val Leu Phe Arg Lys Lys Lys Cys 85 90
95 Asp Tyr Trp Ile Arg Thr Phe Val Pro Gly Cys Gln Pro Gly Glu Phe
100 105 110 Thr Leu Gly Asn Ile Lys Ser Tyr Pro Gly Leu Thr Ser Tyr
Leu Val 115 120 125 Arg Val Val Ser Thr Asn Tyr Asn Gln His Ala Met
Val Phe Phe Lys 130 135 140 Lys Val Ser Gln Asn Arg Glu Tyr Phe Lys
Ile Thr Leu Tyr Gly Arg 145 150 155 160 Thr Lys Glu Leu Thr Ser Glu
Leu Lys Glu Asn Phe Ile Arg Phe Ser 165 170 175 Lys Ser Leu Gly Leu
Pro Glu Asn His Ile Val Phe Pro Val Pro Ile 180 185 190 Gly Asn Gly
Gln Ser Gly 195 55 609 DNA Homo sapiens CDS (4)..(598) 55 atc atg
ccc cta ggt ctc ctg tgg ctg ggc cta gcc ctg ttg ggg gct 48 Met Pro
Leu Gly Leu Leu Trp Leu Gly Leu Ala Leu Leu Gly Ala 1 5 10 15 ctg
cat gcc cag gcc cag gac tcc acc tca gac ctg atc cca gcc cca 96 Leu
His Ala Gln Ala Gln Asp Ser Thr Ser Asp Leu Ile Pro Ala Pro 20 25
30 cct ctg agc aag gtc cct ctg cag cag aac ttc cag gac aac caa ttc
144 Pro Leu Ser Lys Val Pro Leu Gln Gln Asn Phe Gln Asp Asn Gln Phe
35 40 45 cag ggg aag tgg tat gtg gta ggc ctg gca ggg aat gca att
ctc aga 192 Gln Gly Lys Trp Tyr Val Val Gly Leu Ala Gly Asn Ala Ile
Leu Arg 50 55 60 gaa gac aaa gac ccg caa aag atg tat gcc acc atc
tat gag ctg aaa 240 Glu Asp Lys Asp Pro Gln Lys Met Tyr Ala Thr Ile
Tyr Glu Leu Lys 65 70 75 gaa gac aag agc tac aat gtc acc tcc gtc
ctg ttt agg aaa aag aag 288 Glu Asp Lys Ser Tyr Asn Val Thr Ser Val
Leu Phe Arg Lys Lys Lys 80 85 90 95 tgt gac tac tgg atc agg act ttt
gtt cca ggt tgc cag ccc ggc gag 336 Cys Asp Tyr Trp Ile Arg Thr Phe
Val Pro Gly Cys Gln Pro Gly Glu 100 105 110 ttc acg ctg ggc aac att
aag agt tac cct gga tta acg agt tac ctc 384 Phe Thr Leu Gly Asn Ile
Lys Ser Tyr Pro Gly Leu Thr Ser Tyr Leu 115 120 125 gtc cga gtg gtg
agc acc aac tac aac cag cat gct atg gtg ttc ttc 432 Val Arg Val Val
Ser Thr Asn Tyr Asn Gln His Ala Met Val Phe Phe 130 135 140 aag aaa
gtt tct caa aac agg gag tac ttc aag atc acc ctc tac ggg 480 Lys Lys
Val Ser Gln Asn Arg Glu Tyr Phe Lys Ile Thr Leu Tyr Gly 145 150 155
aga acc aag gag ctg act tcg gaa cta aag gag aac ttc atc cgc ttc 528
Arg Thr Lys Glu Leu Thr Ser Glu Leu Lys Glu Asn Phe Ile Arg Phe 160
165 170 175 tcc aaa tct ctg ggc ctc cct gaa aac cac atc gtc ttc cct
gtc cca 576 Ser Lys Ser Leu Gly Leu Pro Glu Asn His Ile Val Phe Pro
Val Pro 180 185 190 atc ggt aat ggc cag tct gga tgaggggacg gg 609
Ile Gly Asn Gly Gln Ser Gly 195 56 198 PRT Homo sapiens 56 Met Pro
Leu Gly Leu Leu Trp Leu Gly Leu Ala Leu Leu Gly Ala Leu 1 5 10 15
His Ala Gln Ala Gln Asp Ser Thr Ser Asp Leu Ile Pro Ala Pro Pro 20
25 30 Leu Ser Lys Val Pro Leu Gln Gln Asn Phe Gln Asp Asn Gln Phe
Gln 35 40 45 Gly Lys Trp Tyr Val Val Gly Leu Ala Gly Asn Ala Ile
Leu Arg Glu 50 55 60 Asp Lys Asp Pro Gln Lys Met Tyr Ala Thr Ile
Tyr Glu Leu Lys Glu 65 70 75 80 Asp Lys Ser Tyr Asn Val Thr Ser Val
Leu Phe Arg Lys Lys Lys Cys 85 90 95 Asp Tyr Trp Ile Arg Thr Phe
Val Pro Gly Cys Gln Pro Gly Glu Phe 100 105 110 Thr Leu Gly Asn Ile
Lys Ser Tyr Pro Gly Leu Thr Ser Tyr Leu Val 115 120 125 Arg Val Val
Ser Thr Asn Tyr Asn Gln His Ala Met Val Phe Phe Lys 130 135 140 Lys
Val Ser Gln Asn Arg Glu Tyr Phe Lys Ile Thr Leu Tyr Gly Arg 145 150
155 160 Thr Lys Glu Leu Thr Ser Glu Leu Lys Glu Asn Phe Ile Arg Phe
Ser 165 170 175 Lys Ser Leu Gly Leu Pro Glu Asn His Ile Val Phe Pro
Val Pro Ile 180 185 190 Gly Asn Gly Gln Ser Gly 195 57 477 DNA Homo
sapiens CDS (1)..(477) 57 cgc gga tcc caa ttc cag ggg aag tgg tat
gtg gta ggc ctg gca ggg 48 Arg Gly Ser Gln Phe Gln Gly Lys Trp Tyr
Val Val Gly Leu Ala Gly 1 5 10 15 aat gca att ctc aga gga gac aaa
gac ccg caa aag atg tat gcc acc 96 Asn Ala Ile Leu Arg Gly Asp Lys
Asp Pro Gln Lys Met Tyr Ala Thr 20 25 30 atc tat gag ctg aaa gaa
gac aag agc tac aat gtc acc tcc gtc ctg 144 Ile Tyr Glu Leu Lys Glu
Asp Lys Ser Tyr Asn Val Thr Ser Val Leu 35 40 45 ttt agg aaa aag
aag tgt gac tac tgg atc agg act ttt gtt cca ggt 192 Phe Arg Lys Lys
Lys Cys Asp Tyr Trp Ile Arg Thr Phe Val Pro Gly 50 55 60 tgc cag
ccc ggc gag ttc acg ctg ggc aac att aag agt tac cct gga 240 Cys Gln
Pro Gly Glu Phe Thr Leu Gly Asn Ile Lys Ser Tyr Pro Gly 65 70 75 80
tta acg agt tac ctc gtc cga gtg gtg agc acc aac tac aac cag cat 288
Leu Thr Ser Tyr Leu Val Arg Val Val Ser Thr Asn Tyr Asn Gln His 85
90 95 gct atg gtg ttc ttc aag aaa gtt tct caa aac agg gag tac ttc
aag 336 Ala Met Val Phe Phe Lys Lys Val Ser Gln Asn Arg Glu Tyr Phe
Lys 100 105 110 atc acc ctc tac ggg aga acc aag gag ctg act tcg gaa
cta aag gag 384 Ile Thr Leu Tyr Gly Arg Thr Lys Glu Leu Thr Ser Glu
Leu Lys Glu 115 120 125 aac ttc atc cgc ttc tcc aaa tct ctg ggc ctc
cct gaa aac cac atc 432 Asn Phe Ile Arg Phe Ser Lys Ser Leu Gly Leu
Pro Glu Asn His Ile 130 135 140 gtc ttc cct gtc cca atc ggt aat ggc
cag tct gga ctc gag gcg 477 Val Phe Pro Val Pro Ile Gly Asn Gly Gln
Ser Gly Leu Glu Ala 145 150 155 58 159 PRT Homo sapiens 58 Arg Gly
Ser Gln Phe Gln Gly Lys Trp Tyr Val Val Gly Leu Ala Gly 1 5 10 15
Asn Ala Ile Leu Arg Gly Asp Lys Asp Pro Gln Lys Met Tyr Ala Thr 20
25 30 Ile Tyr Glu Leu Lys Glu Asp Lys Ser Tyr Asn Val Thr Ser Val
Leu 35 40 45 Phe Arg Lys Lys Lys Cys Asp Tyr Trp Ile Arg Thr Phe
Val Pro Gly 50 55 60 Cys Gln Pro Gly Glu Phe Thr Leu Gly Asn Ile
Lys Ser Tyr Pro Gly 65 70 75 80 Leu Thr Ser Tyr Leu Val Arg Val Val
Ser Thr Asn Tyr Asn Gln His 85 90 95 Ala Met Val Phe Phe Lys Lys
Val Ser Gln Asn Arg Glu Tyr Phe Lys 100 105 110 Ile Thr Leu Tyr Gly
Arg Thr Lys Glu Leu Thr Ser Glu Leu Lys Glu 115 120 125 Asn Phe Ile
Arg Phe Ser Lys Ser Leu Gly Leu Pro Glu Asn His Ile 130 135 140 Val
Phe Pro Val Pro Ile Gly Asn Gly Gln Ser Gly Leu Glu Ala 145 150 155
59 2210 DNA Homo sapiens CDS (1)..(2194) 59 atg aca att tta aga gtg
ttt aac caa gac tgt tcc ttt aaa tgt gtt 48 Met Thr Ile Leu Arg Val
Phe Asn Gln Asp Cys Ser Phe Lys Cys Val 1 5 10 15 ctt ttg ctg ctg
ttt aat tat aca tgt caa tta ttt aca gat cct gtg 96 Leu Leu Leu Leu
Phe Asn Tyr Thr Cys Gln Leu Phe Thr Asp Pro Val 20 25 30 gta ttg
tgg aaa ttc cca gag gac ttt gga gac cag gaa ata cta cag 144 Val Leu
Trp Lys Phe Pro Glu Asp Phe Gly Asp Gln Glu Ile Leu Gln 35 40 45
agt gtg cca aag ttc tgt ttt ccc ttt gac gtt gaa agg tac agt ata 192
Ser Val Pro Lys Phe Cys Phe Pro Phe Asp Val Glu Arg Tyr Ser Ile 50
55 60 agt caa gtt gga cag cac ttt acc ttt gta ctg aca gac att gaa
agt 240 Ser Gln Val Gly Gln His Phe Thr Phe Val Leu Thr Asp Ile Glu
Ser 65 70 75 80 aaa cag aga ttt gga ttc tgc aga ctg acg tca gga ggc
aca att tgt 288 Lys Gln Arg Phe Gly Phe Cys Arg Leu Thr Ser Gly Gly
Thr Ile Cys 85 90 95 tta tgc atc ctt agt tac ctt ccc tgg ttt gaa
gtg tat tac aag ctt 336 Leu Cys Ile Leu Ser Tyr Leu Pro Trp Phe Glu
Val Tyr Tyr Lys Leu 100 105 110 cta aat act ctt gca gat tac ttg gct
aag cat tcc tac ttc att gcc 384 Leu Asn Thr Leu Ala Asp Tyr Leu Ala
Lys His Ser Tyr Phe Ile Ala 115 120 125 cct gat gta act gga ctc cca
aca ata ccc gag agt aga aat ctt aca 432 Pro Asp Val Thr Gly Leu Pro
Thr Ile Pro Glu Ser Arg Asn Leu Thr 130 135 140 gaa tat ttt gtt gcc
gtg gat gtg aac aac atg ctg cag ctg tat gcc 480 Glu Tyr Phe Val Ala
Val Asp Val Asn Asn Met Leu Gln Leu Tyr Ala 145 150 155 160 agt atg
ctg cat gaa agg cgc atc gtg att atc tcg agc aaa tta agc 528 Ser Met
Leu His Glu Arg Arg Ile Val Ile Ile Ser Ser Lys Leu Ser 165 170 175
act tta act gcc tgt atc cat gga tca gct gct ctt cta tac cca atg 576
Thr Leu Thr Ala Cys Ile His Gly Ser Ala Ala Leu Leu Tyr Pro Met 180
185 190 tat tgg caa cac ata tac atc cca gtg ctt cct cca cac ctg ctg
gac 624 Tyr Trp Gln His Ile Tyr Ile Pro Val Leu Pro Pro His Leu Leu
Asp 195 200 205 tac tgc agt gcc cca atg cca tac ctg att gga ata cac
tcc agc ctc 672 Tyr Cys Ser Ala Pro Met Pro Tyr Leu Ile Gly Ile His
Ser Ser Leu 210 215 220 ata gag aga gtg aaa aac aaa tca ttg gaa gat
gtt gtt atg tta aat 720 Ile Glu Arg Val Lys Asn Lys Ser Leu Glu Asp
Val Val Met Leu Asn 225 230 235 240 gtt gat aca aac aca tta gaa tca
cca ttt agt gac ttg aac aac cta 768 Val Asp Thr Asn Thr Leu Glu Ser
Pro Phe Ser Asp Leu Asn Asn Leu 245 250 255 cca agt gat gtg gta agt
gcc ttg aaa aat aaa ctg aag aag cag tct 816 Pro Ser Asp Val Val Ser
Ala Leu Lys Asn Lys Leu Lys Lys Gln Ser 260 265 270 aca gct acg ggt
gat gga gta gct agg gcc ttt ctt aga gca cag gct 864 Thr Ala Thr Gly
Asp Gly Val Ala Arg Ala Phe Leu Arg Ala Gln Ala 275 280 285 gct ttg
ttt gga tcc tac aga gat gca ctg aga tac aaa cct ggt gag 912 Ala Leu
Phe Gly Ser Tyr Arg Asp Ala Leu Arg Tyr Lys Pro Gly Glu 290 295 300
ccc atc act ttc tgt gag gag agt ttt gta aag cac cgc tca agc gtg 960
Pro Ile Thr Phe Cys Glu Glu Ser Phe Val Lys His Arg Ser Ser Val 305
310 315 320 atg aaa cag ttc ctg gaa act gcc att aac ctc cag ctt ttt
aag cag 1008 Met Lys Gln Phe Leu Glu Thr Ala Ile Asn Leu Gln Leu
Phe Lys Gln 325 330 335 gta ttt atc gat ggt cga ctg gca aaa cta aat
gca gga agg ggt ttc 1056 Val Phe Ile Asp Gly Arg Leu Ala Lys Leu
Asn Ala Gly Arg Gly Phe 340 345 350 tct gat gta ttt gaa gaa gag atc
act tca ggt ggc ttt tgt gga ggt 1104 Ser Asp Val Phe Glu Glu Glu
Ile Thr Ser Gly Gly Phe Cys Gly Gly 355 360 365 aaa gac aag tta caa
tat aaa tat gtt tct gtt ttt ctt ttg cag aaa 1152 Lys Asp Lys Leu
Gln Tyr Lys Tyr Val Ser Val Phe Leu Leu Gln Lys 370 375 380 gga ggt
gca ctg ttc aac aca gca atg acc aaa gca acc cct gct gta 1200 Gly
Gly Ala Leu Phe Asn Thr Ala Met Thr Lys Ala Thr Pro Ala Val 385 390
395 400 cgg aca gca tat aaa ttt gca aaa aat cat gca aag ctg gga cta
aag 1248 Arg Thr Ala Tyr Lys Phe Ala Lys Asn His Ala Lys Leu Gly
Leu Lys 405 410 415 gaa gtg aag agt aaa cta aaa cac aag gaa aat gaa
gaa gat tat ggg 1296 Glu Val Lys Ser Lys Leu Lys His Lys Glu Asn
Glu Glu Asp Tyr Gly 420 425 430 acc tgt tct agt tct gta caa tat aca
cca gtt tac aaa tta cac aat 1344 Thr Cys Ser Ser Ser Val Gln Tyr
Thr Pro Val Tyr Lys Leu His Asn 435 440 445 gaa aag gga gga aac tca
gaa aag cgt aag ctt gct cag gca cgc tta 1392 Glu Lys Gly Gly Asn
Ser Glu Lys Arg Lys Leu Ala Gln Ala Arg Leu 450 455 460 aaa agg cct
ctt aag agc ctt gat ggt gct cta tat gat gat gaa gat 1440 Lys Arg
Pro Leu Lys Ser Leu Asp Gly Ala Leu Tyr Asp Asp Glu Asp 465 470 475
480 gat gat gac att gaa aga gca agc aag tta tct tct gaa gat ggt gaa
1488 Asp Asp Asp Ile Glu Arg Ala Ser Lys Leu Ser Ser Glu Asp Gly
Glu 485 490 495 gaa gct tct gct tat ctc tat gag agt gat gac tct gtt
gaa aca aga 1536 Glu Ala Ser Ala Tyr Leu Tyr Glu Ser Asp Asp Ser
Val Glu Thr Arg 500 505 510 gtg aag act cct tac tca ggt gaa atg gac
tta cta gga gag att ctt 1584 Val Lys Thr Pro Tyr Ser Gly Glu Met
Asp Leu Leu Gly Glu Ile Leu 515 520 525 gat aca ttg agc aca cac agc
tca gat cag ggg aag ctg gca gct gca 1632 Asp Thr Leu Ser Thr His
Ser Ser Asp Gln Gly Lys Leu Ala Ala Ala 530 535 540 aag agc ttg gat
ttc ttt aga tca atg gat gac att gat tac aaa cct 1680 Lys Ser Leu
Asp Phe Phe Arg Ser Met Asp Asp Ile Asp Tyr Lys Pro 545 550 555 560
acg aat aaa tct aat gct cct agt gag aat aac ctg gct ttc ctc tgt
1728 Thr Asn Lys Ser Asn Ala Pro Ser Glu Asn Asn Leu Ala Phe Leu
Cys 565 570 575 ggt ggt tct ggt gac caa gca gag tgg aat ctt ggg caa
gac gat agt 1776 Gly Gly Ser Gly Asp Gln Ala Glu Trp Asn Leu Gly
Gln Asp Asp Ser 580 585 590 gcc ctc cat ggc aaa cac ctc cct cca tct
cct agg aag cgg gtt tcc 1824 Ala Leu His Gly Lys His Leu Pro Pro
Ser Pro Arg Lys Arg Val Ser 595 600 605 tct agt ggt ttg aca gat tct
ctg ttt atc ctg aga gag gaa aac agt 1872 Ser Ser Gly Leu Thr Asp
Ser Leu Phe Ile Leu Arg Glu Glu Asn Ser 610 615 620 aac aag cac ctc
ggt gct gac aat gtg agt gac cct act tca gga ctg 1920 Asn Lys His
Leu Gly Ala Asp Asn Val Ser Asp Pro Thr Ser Gly Leu 625 630 635 640
gat ttc caa ctc act tcc cct gaa gtt tcc cag act gat aaa gga aaa
1968 Asp Phe Gln Leu Thr Ser Pro Glu Val Ser Gln Thr Asp Lys Gly
Lys 645 650 655 aca gaa aag agg
gaa aca cta agc cag att tca gat gat ctg ctt ata 2016 Thr Glu Lys
Arg Glu Thr Leu Ser Gln Ile Ser Asp Asp Leu Leu Ile 660 665 670 ccc
ggt ctt ggg cgg cat tca tcg act ttt gtt cct tgg gag aaa gaa 2064
Pro Gly Leu Gly Arg His Ser Ser Thr Phe Val Pro Trp Glu Lys Glu 675
680 685 ggg aaa gaa gcc aaa gag act tca gaa gat att gga ctg ctc cat
gaa 2112 Gly Lys Glu Ala Lys Glu Thr Ser Glu Asp Ile Gly Leu Leu
His Glu 690 695 700 gta gtg tca tta tgt cat atg aca tct gac ttc caa
caa agc ttg aac 2160 Val Val Ser Leu Cys His Met Thr Ser Asp Phe
Gln Gln Ser Leu Asn 705 710 715 720 att tca gac aaa aac aca aat gga
aac caa act taaatcttgc 2203 Ile Ser Asp Lys Asn Thr Asn Gly Asn Gln
Thr 725 730 atccaag 2210 60 731 PRT Homo sapiens 60 Met Thr Ile Leu
Arg Val Phe Asn Gln Asp Cys Ser Phe Lys Cys Val 1 5 10 15 Leu Leu
Leu Leu Phe Asn Tyr Thr Cys Gln Leu Phe Thr Asp Pro Val 20 25 30
Val Leu Trp Lys Phe Pro Glu Asp Phe Gly Asp Gln Glu Ile Leu Gln 35
40 45 Ser Val Pro Lys Phe Cys Phe Pro Phe Asp Val Glu Arg Tyr Ser
Ile 50 55 60 Ser Gln Val Gly Gln His Phe Thr Phe Val Leu Thr Asp
Ile Glu Ser 65 70 75 80 Lys Gln Arg Phe Gly Phe Cys Arg Leu Thr Ser
Gly Gly Thr Ile Cys 85 90 95 Leu Cys Ile Leu Ser Tyr Leu Pro Trp
Phe Glu Val Tyr Tyr Lys Leu 100 105 110 Leu Asn Thr Leu Ala Asp Tyr
Leu Ala Lys His Ser Tyr Phe Ile Ala 115 120 125 Pro Asp Val Thr Gly
Leu Pro Thr Ile Pro Glu Ser Arg Asn Leu Thr 130 135 140 Glu Tyr Phe
Val Ala Val Asp Val Asn Asn Met Leu Gln Leu Tyr Ala 145 150 155 160
Ser Met Leu His Glu Arg Arg Ile Val Ile Ile Ser Ser Lys Leu Ser 165
170 175 Thr Leu Thr Ala Cys Ile His Gly Ser Ala Ala Leu Leu Tyr Pro
Met 180 185 190 Tyr Trp Gln His Ile Tyr Ile Pro Val Leu Pro Pro His
Leu Leu Asp 195 200 205 Tyr Cys Ser Ala Pro Met Pro Tyr Leu Ile Gly
Ile His Ser Ser Leu 210 215 220 Ile Glu Arg Val Lys Asn Lys Ser Leu
Glu Asp Val Val Met Leu Asn 225 230 235 240 Val Asp Thr Asn Thr Leu
Glu Ser Pro Phe Ser Asp Leu Asn Asn Leu 245 250 255 Pro Ser Asp Val
Val Ser Ala Leu Lys Asn Lys Leu Lys Lys Gln Ser 260 265 270 Thr Ala
Thr Gly Asp Gly Val Ala Arg Ala Phe Leu Arg Ala Gln Ala 275 280 285
Ala Leu Phe Gly Ser Tyr Arg Asp Ala Leu Arg Tyr Lys Pro Gly Glu 290
295 300 Pro Ile Thr Phe Cys Glu Glu Ser Phe Val Lys His Arg Ser Ser
Val 305 310 315 320 Met Lys Gln Phe Leu Glu Thr Ala Ile Asn Leu Gln
Leu Phe Lys Gln 325 330 335 Val Phe Ile Asp Gly Arg Leu Ala Lys Leu
Asn Ala Gly Arg Gly Phe 340 345 350 Ser Asp Val Phe Glu Glu Glu Ile
Thr Ser Gly Gly Phe Cys Gly Gly 355 360 365 Lys Asp Lys Leu Gln Tyr
Lys Tyr Val Ser Val Phe Leu Leu Gln Lys 370 375 380 Gly Gly Ala Leu
Phe Asn Thr Ala Met Thr Lys Ala Thr Pro Ala Val 385 390 395 400 Arg
Thr Ala Tyr Lys Phe Ala Lys Asn His Ala Lys Leu Gly Leu Lys 405 410
415 Glu Val Lys Ser Lys Leu Lys His Lys Glu Asn Glu Glu Asp Tyr Gly
420 425 430 Thr Cys Ser Ser Ser Val Gln Tyr Thr Pro Val Tyr Lys Leu
His Asn 435 440 445 Glu Lys Gly Gly Asn Ser Glu Lys Arg Lys Leu Ala
Gln Ala Arg Leu 450 455 460 Lys Arg Pro Leu Lys Ser Leu Asp Gly Ala
Leu Tyr Asp Asp Glu Asp 465 470 475 480 Asp Asp Asp Ile Glu Arg Ala
Ser Lys Leu Ser Ser Glu Asp Gly Glu 485 490 495 Glu Ala Ser Ala Tyr
Leu Tyr Glu Ser Asp Asp Ser Val Glu Thr Arg 500 505 510 Val Lys Thr
Pro Tyr Ser Gly Glu Met Asp Leu Leu Gly Glu Ile Leu 515 520 525 Asp
Thr Leu Ser Thr His Ser Ser Asp Gln Gly Lys Leu Ala Ala Ala 530 535
540 Lys Ser Leu Asp Phe Phe Arg Ser Met Asp Asp Ile Asp Tyr Lys Pro
545 550 555 560 Thr Asn Lys Ser Asn Ala Pro Ser Glu Asn Asn Leu Ala
Phe Leu Cys 565 570 575 Gly Gly Ser Gly Asp Gln Ala Glu Trp Asn Leu
Gly Gln Asp Asp Ser 580 585 590 Ala Leu His Gly Lys His Leu Pro Pro
Ser Pro Arg Lys Arg Val Ser 595 600 605 Ser Ser Gly Leu Thr Asp Ser
Leu Phe Ile Leu Arg Glu Glu Asn Ser 610 615 620 Asn Lys His Leu Gly
Ala Asp Asn Val Ser Asp Pro Thr Ser Gly Leu 625 630 635 640 Asp Phe
Gln Leu Thr Ser Pro Glu Val Ser Gln Thr Asp Lys Gly Lys 645 650 655
Thr Glu Lys Arg Glu Thr Leu Ser Gln Ile Ser Asp Asp Leu Leu Ile 660
665 670 Pro Gly Leu Gly Arg His Ser Ser Thr Phe Val Pro Trp Glu Lys
Glu 675 680 685 Gly Lys Glu Ala Lys Glu Thr Ser Glu Asp Ile Gly Leu
Leu His Glu 690 695 700 Val Val Ser Leu Cys His Met Thr Ser Asp Phe
Gln Gln Ser Leu Asn 705 710 715 720 Ile Ser Asp Lys Asn Thr Asn Gly
Asn Gln Thr 725 730 61 2256 DNA Homo sapiens CDS (1)..(2256) 61 aga
tct gat cct gtg gta ttg tgg aaa ttc cca gag gac ttt gga gac 48 Arg
Ser Asp Pro Val Val Leu Trp Lys Phe Pro Glu Asp Phe Gly Asp 1 5 10
15 cag gaa ata cta cag agt gtg cca aag ttc tgt ttt ccc ttt gac gtt
96 Gln Glu Ile Leu Gln Ser Val Pro Lys Phe Cys Phe Pro Phe Asp Val
20 25 30 gaa agg gtg tct cag aat caa gtt gga cag cac ttt acc ttt
gta ctg 144 Glu Arg Val Ser Gln Asn Gln Val Gly Gln His Phe Thr Phe
Val Leu 35 40 45 aca gac att gaa agt aaa cag aga ttt gga ttc tgc
aga ctg acg tca 192 Thr Asp Ile Glu Ser Lys Gln Arg Phe Gly Phe Cys
Arg Leu Thr Ser 50 55 60 gga ggc aca att tgt tta tgc atc ctt agt
tac ctt ccc tgg ttt gaa 240 Gly Gly Thr Ile Cys Leu Cys Ile Leu Ser
Tyr Leu Pro Trp Phe Glu 65 70 75 80 gtg tat tac aag ctt cta aat act
ctt gca gat tac ttg gct aag gaa 288 Val Tyr Tyr Lys Leu Leu Asn Thr
Leu Ala Asp Tyr Leu Ala Lys Glu 85 90 95 ctg gaa aat gat ttg aat
gaa act ctc aga tca ctg tat aac cac cca 336 Leu Glu Asn Asp Leu Asn
Glu Thr Leu Arg Ser Leu Tyr Asn His Pro 100 105 110 gta cca aag gca
aat act cct gta aat ttg agt gtg aac caa gag ata 384 Val Pro Lys Ala
Asn Thr Pro Val Asn Leu Ser Val Asn Gln Glu Ile 115 120 125 ttt att
acc tgt gag caa gtt ctg aaa gat cag cct gct cta cta ccg 432 Phe Ile
Thr Cys Glu Gln Val Leu Lys Asp Gln Pro Ala Leu Leu Pro 130 135 140
cat tcc tac ttc att gcc cct gat gta act gga ctc cca aca ata ccc 480
His Ser Tyr Phe Ile Ala Pro Asp Val Thr Gly Leu Pro Thr Ile Pro 145
150 155 160 gag agt aga aat ctt aca gaa tat ttt gtt gcc gtg gat gtg
aac aac 528 Glu Ser Arg Asn Leu Thr Glu Tyr Phe Val Ala Val Asp Val
Asn Asn 165 170 175 atg ctg cag ctg tat gcc agt atg ctg cat gaa agg
cgc atc gtg att 576 Met Leu Gln Leu Tyr Ala Ser Met Leu His Glu Arg
Arg Ile Val Ile 180 185 190 atc tcg agc aaa tta agc act tta act gcc
tgt atc cat gga tca gct 624 Ile Ser Ser Lys Leu Ser Thr Leu Thr Ala
Cys Ile His Gly Ser Ala 195 200 205 gct ctt cta tac cca atg tat tgg
caa cac ata tac atc cca gtg ctt 672 Ala Leu Leu Tyr Pro Met Tyr Trp
Gln His Ile Tyr Ile Pro Val Leu 210 215 220 cct cca cac ctg ctg gac
tac tgc tgt gcc cca atg cca tac ctg att 720 Pro Pro His Leu Leu Asp
Tyr Cys Cys Ala Pro Met Pro Tyr Leu Ile 225 230 235 240 gga ata cac
tcc agc ctc ata gag aga gtg aaa aac aaa tca ttg gaa 768 Gly Ile His
Ser Ser Leu Ile Glu Arg Val Lys Asn Lys Ser Leu Glu 245 250 255 gat
gtt gtt atg tta aat gtt gat aca aac aca tta gaa tca cca ttt 816 Asp
Val Val Met Leu Asn Val Asp Thr Asn Thr Leu Glu Ser Pro Phe 260 265
270 agt gac ttg aac aac cta cca agt gat gtg gtc tcg gcc ttg aaa aat
864 Ser Asp Leu Asn Asn Leu Pro Ser Asp Val Val Ser Ala Leu Lys Asn
275 280 285 aaa ctg aag aag cag tct aca gct acg ggt gat gga gta gct
agg gcc 912 Lys Leu Lys Lys Gln Ser Thr Ala Thr Gly Asp Gly Val Ala
Arg Ala 290 295 300 ttt ctt aga gca cag gct gct ttg ttt gga tcc tac
aga gat gca ctg 960 Phe Leu Arg Ala Gln Ala Ala Leu Phe Gly Ser Tyr
Arg Asp Ala Leu 305 310 315 320 aga tac aaa cct ggt gag ccc atc act
ttc tgt gag gag agt ttt gta 1008 Arg Tyr Lys Pro Gly Glu Pro Ile
Thr Phe Cys Glu Glu Ser Phe Val 325 330 335 aag cac cgc tca agc gtg
atg aaa cag ttc ctg gaa act gcc att aac 1056 Lys His Arg Ser Ser
Val Met Lys Gln Phe Leu Glu Thr Ala Ile Asn 340 345 350 ctc cag ctt
ttt aag cag ttt atc gat ggt cga ctg gca aaa cta aat 1104 Leu Gln
Leu Phe Lys Gln Phe Ile Asp Gly Arg Leu Ala Lys Leu Asn 355 360 365
gca gga agg ggt ttc tct gat gta ttt gaa gaa gag atc act tca ggt
1152 Ala Gly Arg Gly Phe Ser Asp Val Phe Glu Glu Glu Ile Thr Ser
Gly 370 375 380 ggc ttt tgt gga ggg aac ccg agg tca tat caa caa tgg
gtg cat aca 1200 Gly Phe Cys Gly Gly Asn Pro Arg Ser Tyr Gln Gln
Trp Val His Thr 385 390 395 400 gtc aag aaa gga ggt gca ctg ttc aac
aca gca atg acc aaa gca acc 1248 Val Lys Lys Gly Gly Ala Leu Phe
Asn Thr Ala Met Thr Lys Ala Thr 405 410 415 cct gct gta cgg aca gca
tat aaa ttt gca aaa aat cat gca aag ctg 1296 Pro Ala Val Arg Thr
Ala Tyr Lys Phe Ala Lys Asn His Ala Lys Leu 420 425 430 gga cta aag
gaa gtg aag agt aaa cta aaa cac aag gaa aat gaa gaa 1344 Gly Leu
Lys Glu Val Lys Ser Lys Leu Lys His Lys Glu Asn Glu Glu 435 440 445
gat tat ggg acc tgt tct agt tct gta caa tat aca cca gtt tac aaa
1392 Asp Tyr Gly Thr Cys Ser Ser Ser Val Gln Tyr Thr Pro Val Tyr
Lys 450 455 460 tta cac aat gaa aag gga gga aac tca gaa aag cgt aag
ctt gct cag 1440 Leu His Asn Glu Lys Gly Gly Asn Ser Glu Lys Arg
Lys Leu Ala Gln 465 470 475 480 gca cgc tta aaa agg cct ctt aag agc
ctt gat ggt gct cta tat gat 1488 Ala Arg Leu Lys Arg Pro Leu Lys
Ser Leu Asp Gly Ala Leu Tyr Asp 485 490 495 gat gaa gat gat gat gac
att gaa aga gca agc aag tta tct tct gaa 1536 Asp Glu Asp Asp Asp
Asp Ile Glu Arg Ala Ser Lys Leu Ser Ser Glu 500 505 510 gat ggt gaa
gaa gct tct gct tat ctc tat gag agt gat gac tct gtt 1584 Asp Gly
Glu Glu Ala Ser Ala Tyr Leu Tyr Glu Ser Asp Asp Ser Val 515 520 525
gaa aca aga gtg aag act cct tac tca ggt gaa atg gac tta cta gga
1632 Glu Thr Arg Val Lys Thr Pro Tyr Ser Gly Glu Met Asp Leu Leu
Gly 530 535 540 gag att ctt gat aca ttg agc aca cac agc tca gat cag
ggg agg ctg 1680 Glu Ile Leu Asp Thr Leu Ser Thr His Ser Ser Asp
Gln Gly Arg Leu 545 550 555 560 gca gct gca aag agc ttg gat ttc ttt
aga tca atg gac gac att gat 1728 Ala Ala Ala Lys Ser Leu Asp Phe
Phe Arg Ser Met Asp Asp Ile Asp 565 570 575 tac aaa cct acg aat aaa
tct aat gct cct agt gag aat aac ctg gct 1776 Tyr Lys Pro Thr Asn
Lys Ser Asn Ala Pro Ser Glu Asn Asn Leu Ala 580 585 590 ttc ctc tgt
ggt ggt tct ggt gac caa gca gag tgg aat ctt ggg caa 1824 Phe Leu
Cys Gly Gly Ser Gly Asp Gln Ala Glu Trp Asn Leu Gly Gln 595 600 605
gac gat agt gcc ctc cat ggc aaa cac ctc cct cca tct cct agg aag
1872 Asp Asp Ser Ala Leu His Gly Lys His Leu Pro Pro Ser Pro Arg
Lys 610 615 620 cgg gtt tcc tct agt ggt ttg aca gat tct ctg ttt atc
ctg aaa gag 1920 Arg Val Ser Ser Ser Gly Leu Thr Asp Ser Leu Phe
Ile Leu Lys Glu 625 630 635 640 gaa aac agt aac aag cac ctc ggt gct
gac aat gtg agt gac cct act 1968 Glu Asn Ser Asn Lys His Leu Gly
Ala Asp Asn Val Ser Asp Pro Thr 645 650 655 tca gga ctg gat ttc caa
ctc act tcc cct gaa gtt tcc cag act gat 2016 Ser Gly Leu Asp Phe
Gln Leu Thr Ser Pro Glu Val Ser Gln Thr Asp 660 665 670 aaa gga aaa
aca gaa aag agg gaa aca cta agc cag att tca gat gat 2064 Lys Gly
Lys Thr Glu Lys Arg Glu Thr Leu Ser Gln Ile Ser Asp Asp 675 680 685
ctg ctt ata ccc ggt ctt ggg cgg cat tca tcg act ttt gtt cct tgg
2112 Leu Leu Ile Pro Gly Leu Gly Arg His Ser Ser Thr Phe Val Pro
Trp 690 695 700 gag aaa gaa ggg aaa gaa gcc aaa gag act tca gaa gat
att gga ctg 2160 Glu Lys Glu Gly Lys Glu Ala Lys Glu Thr Ser Glu
Asp Ile Gly Leu 705 710 715 720 ctc cat gaa gta gtg tca tta tgt cat
atg aca tct gac ttc caa caa 2208 Leu His Glu Val Val Ser Leu Cys
His Met Thr Ser Asp Phe Gln Gln 725 730 735 agc ttg aac att tca gac
aaa aac aca aat gga aac caa act aga tct 2256 Ser Leu Asn Ile Ser
Asp Lys Asn Thr Asn Gly Asn Gln Thr Arg Ser 740 745 750 62 752 PRT
Homo sapiens 62 Arg Ser Asp Pro Val Val Leu Trp Lys Phe Pro Glu Asp
Phe Gly Asp 1 5 10 15 Gln Glu Ile Leu Gln Ser Val Pro Lys Phe Cys
Phe Pro Phe Asp Val 20 25 30 Glu Arg Val Ser Gln Asn Gln Val Gly
Gln His Phe Thr Phe Val Leu 35 40 45 Thr Asp Ile Glu Ser Lys Gln
Arg Phe Gly Phe Cys Arg Leu Thr Ser 50 55 60 Gly Gly Thr Ile Cys
Leu Cys Ile Leu Ser Tyr Leu Pro Trp Phe Glu 65 70 75 80 Val Tyr Tyr
Lys Leu Leu Asn Thr Leu Ala Asp Tyr Leu Ala Lys Glu 85 90 95 Leu
Glu Asn Asp Leu Asn Glu Thr Leu Arg Ser Leu Tyr Asn His Pro 100 105
110 Val Pro Lys Ala Asn Thr Pro Val Asn Leu Ser Val Asn Gln Glu Ile
115 120 125 Phe Ile Thr Cys Glu Gln Val Leu Lys Asp Gln Pro Ala Leu
Leu Pro 130 135 140 His Ser Tyr Phe Ile Ala Pro Asp Val Thr Gly Leu
Pro Thr Ile Pro 145 150 155 160 Glu Ser Arg Asn Leu Thr Glu Tyr Phe
Val Ala Val Asp Val Asn Asn 165 170 175 Met Leu Gln Leu Tyr Ala Ser
Met Leu His Glu Arg Arg Ile Val Ile 180 185 190 Ile Ser Ser Lys Leu
Ser Thr Leu Thr Ala Cys Ile His Gly Ser Ala 195 200 205 Ala Leu Leu
Tyr Pro Met Tyr Trp Gln His Ile Tyr Ile Pro Val Leu 210 215 220 Pro
Pro His Leu Leu Asp Tyr Cys Cys Ala Pro Met Pro Tyr Leu Ile 225 230
235 240 Gly Ile His Ser Ser Leu Ile Glu Arg Val Lys Asn Lys Ser Leu
Glu 245 250 255 Asp Val Val Met Leu Asn Val Asp Thr Asn Thr Leu Glu
Ser Pro Phe 260 265 270 Ser Asp Leu Asn Asn Leu Pro Ser Asp Val Val
Ser Ala Leu Lys Asn 275 280 285 Lys Leu Lys Lys Gln Ser Thr Ala Thr
Gly Asp Gly Val Ala Arg Ala 290 295 300 Phe Leu Arg Ala Gln Ala Ala
Leu Phe Gly Ser Tyr Arg Asp Ala Leu 305 310 315 320 Arg Tyr Lys Pro
Gly Glu Pro Ile Thr Phe Cys Glu Glu Ser Phe Val 325 330 335 Lys His
Arg Ser Ser Val Met Lys Gln Phe Leu Glu Thr Ala Ile Asn 340 345 350
Leu Gln Leu Phe Lys Gln Phe Ile Asp Gly Arg Leu Ala Lys Leu Asn
355
360 365 Ala Gly Arg Gly Phe Ser Asp Val Phe Glu Glu Glu Ile Thr Ser
Gly 370 375 380 Gly Phe Cys Gly Gly Asn Pro Arg Ser Tyr Gln Gln Trp
Val His Thr 385 390 395 400 Val Lys Lys Gly Gly Ala Leu Phe Asn Thr
Ala Met Thr Lys Ala Thr 405 410 415 Pro Ala Val Arg Thr Ala Tyr Lys
Phe Ala Lys Asn His Ala Lys Leu 420 425 430 Gly Leu Lys Glu Val Lys
Ser Lys Leu Lys His Lys Glu Asn Glu Glu 435 440 445 Asp Tyr Gly Thr
Cys Ser Ser Ser Val Gln Tyr Thr Pro Val Tyr Lys 450 455 460 Leu His
Asn Glu Lys Gly Gly Asn Ser Glu Lys Arg Lys Leu Ala Gln 465 470 475
480 Ala Arg Leu Lys Arg Pro Leu Lys Ser Leu Asp Gly Ala Leu Tyr Asp
485 490 495 Asp Glu Asp Asp Asp Asp Ile Glu Arg Ala Ser Lys Leu Ser
Ser Glu 500 505 510 Asp Gly Glu Glu Ala Ser Ala Tyr Leu Tyr Glu Ser
Asp Asp Ser Val 515 520 525 Glu Thr Arg Val Lys Thr Pro Tyr Ser Gly
Glu Met Asp Leu Leu Gly 530 535 540 Glu Ile Leu Asp Thr Leu Ser Thr
His Ser Ser Asp Gln Gly Arg Leu 545 550 555 560 Ala Ala Ala Lys Ser
Leu Asp Phe Phe Arg Ser Met Asp Asp Ile Asp 565 570 575 Tyr Lys Pro
Thr Asn Lys Ser Asn Ala Pro Ser Glu Asn Asn Leu Ala 580 585 590 Phe
Leu Cys Gly Gly Ser Gly Asp Gln Ala Glu Trp Asn Leu Gly Gln 595 600
605 Asp Asp Ser Ala Leu His Gly Lys His Leu Pro Pro Ser Pro Arg Lys
610 615 620 Arg Val Ser Ser Ser Gly Leu Thr Asp Ser Leu Phe Ile Leu
Lys Glu 625 630 635 640 Glu Asn Ser Asn Lys His Leu Gly Ala Asp Asn
Val Ser Asp Pro Thr 645 650 655 Ser Gly Leu Asp Phe Gln Leu Thr Ser
Pro Glu Val Ser Gln Thr Asp 660 665 670 Lys Gly Lys Thr Glu Lys Arg
Glu Thr Leu Ser Gln Ile Ser Asp Asp 675 680 685 Leu Leu Ile Pro Gly
Leu Gly Arg His Ser Ser Thr Phe Val Pro Trp 690 695 700 Glu Lys Glu
Gly Lys Glu Ala Lys Glu Thr Ser Glu Asp Ile Gly Leu 705 710 715 720
Leu His Glu Val Val Ser Leu Cys His Met Thr Ser Asp Phe Gln Gln 725
730 735 Ser Leu Asn Ile Ser Asp Lys Asn Thr Asn Gly Asn Gln Thr Arg
Ser 740 745 750 63 2256 DNA Homo sapiens CDS (1)..(2256) 63 aga tct
gat cct gtg gta ttg tgg aaa ttc cca gag gac ttt gga gac 48 Arg Ser
Asp Pro Val Val Leu Trp Lys Phe Pro Glu Asp Phe Gly Asp 1 5 10 15
cag gaa ata cta cag agt gtg cca aag ttc tgt ttt ccc ttt gac gtt 96
Gln Glu Ile Leu Gln Ser Val Pro Lys Phe Cys Phe Pro Phe Asp Val 20
25 30 gaa agg gtg tct cag aat caa gtt gga cag cac ttt acc ttt gta
ctg 144 Glu Arg Val Ser Gln Asn Gln Val Gly Gln His Phe Thr Phe Val
Leu 35 40 45 aca gac att gaa agt aaa cag aga ttt gga ttc tgc aga
ctg acg tca 192 Thr Asp Ile Glu Ser Lys Gln Arg Phe Gly Phe Cys Arg
Leu Thr Ser 50 55 60 gga ggc aca att tgt tta tgc atc ctt agt tac
ctt ccc tgg ttt gaa 240 Gly Gly Thr Ile Cys Leu Cys Ile Leu Ser Tyr
Leu Pro Trp Phe Glu 65 70 75 80 gtg tat tac aag ctt cta aat act ctt
gca gat tac ttg gct aag gaa 288 Val Tyr Tyr Lys Leu Leu Asn Thr Leu
Ala Asp Tyr Leu Ala Lys Glu 85 90 95 ctg gaa aat gat ttg aat gaa
act ctc aga tca ctg tat aac cac cca 336 Leu Glu Asn Asp Leu Asn Glu
Thr Leu Arg Ser Leu Tyr Asn His Pro 100 105 110 gta cca aag gca aat
act cct gta aat ttg agt gtg aac caa gag ata 384 Val Pro Lys Ala Asn
Thr Pro Val Asn Leu Ser Val Asn Gln Glu Ile 115 120 125 ttt att acc
tgt gag caa gtt ctg aaa gat cag cct gct cta cta ccg 432 Phe Ile Thr
Cys Glu Gln Val Leu Lys Asp Gln Pro Ala Leu Leu Pro 130 135 140 cat
tcc tac ttc att gcc cct gat gta act gga ctc cca aca ata ccc 480 His
Ser Tyr Phe Ile Ala Pro Asp Val Thr Gly Leu Pro Thr Ile Pro 145 150
155 160 gag agt aga aat ctt aca gaa tat ttt gtt gcc gtg gat gtg aac
aac 528 Glu Ser Arg Asn Leu Thr Glu Tyr Phe Val Ala Val Asp Val Asn
Asn 165 170 175 atg ctg cag ctg tat gcc agt atg ctg cat gaa agg cgc
atc gtg att 576 Met Leu Gln Leu Tyr Ala Ser Met Leu His Glu Arg Arg
Ile Val Ile 180 185 190 atc tcg agc aaa tta agc act tta act gcc tgt
atc cat gga tca gct 624 Ile Ser Ser Lys Leu Ser Thr Leu Thr Ala Cys
Ile His Gly Ser Ala 195 200 205 gct ctt cta tac cca atg tat tgg caa
cac ata tac atc cca gtg ctt 672 Ala Leu Leu Tyr Pro Met Tyr Trp Gln
His Ile Tyr Ile Pro Val Leu 210 215 220 cct cca cac ctg ctg gac tac
tgc tgt gcc cca atg cca tac ctg att 720 Pro Pro His Leu Leu Asp Tyr
Cys Cys Ala Pro Met Pro Tyr Leu Ile 225 230 235 240 gga ata cac tcc
agc ctc ata gag aga gtg aaa aac aaa tca ttg gaa 768 Gly Ile His Ser
Ser Leu Ile Glu Arg Val Lys Asn Lys Ser Leu Glu 245 250 255 gat gtt
gtt atg tta aat gtt gat aca aac aca tta gaa tca cca ttt 816 Asp Val
Val Met Leu Asn Val Asp Thr Asn Thr Leu Glu Ser Pro Phe 260 265 270
agt gac ttg aac aac cta cca agt gat gtg gtc tcg gcc ttg aaa aat 864
Ser Asp Leu Asn Asn Leu Pro Ser Asp Val Val Ser Ala Leu Lys Asn 275
280 285 aaa ctg aag aag cag tct aca gct acg ggt gat gga gta gct agg
gcc 912 Lys Leu Lys Lys Gln Ser Thr Ala Thr Gly Asp Gly Val Ala Arg
Ala 290 295 300 ttt ctt aga gca cag gct gct ttg ttt gga tcc tac aga
gat gca ctg 960 Phe Leu Arg Ala Gln Ala Ala Leu Phe Gly Ser Tyr Arg
Asp Ala Leu 305 310 315 320 aga tac aaa cct ggt gag ccc atc act ttc
tgt gag gag agt ttt gta 1008 Arg Tyr Lys Pro Gly Glu Pro Ile Thr
Phe Cys Glu Glu Ser Phe Val 325 330 335 aag cac cgc tca agc gtg atg
aaa cag ttc ctg gaa act gcc att aac 1056 Lys His Arg Ser Ser Val
Met Lys Gln Phe Leu Glu Thr Ala Ile Asn 340 345 350 ctc cag ctt ttt
aag cag ttt atc gat ggt cga ctg gca aaa cta aat 1104 Leu Gln Leu
Phe Lys Gln Phe Ile Asp Gly Arg Leu Ala Lys Leu Asn 355 360 365 gca
gga agg ggt ttc tct gat gta ttt gaa gaa gag atc act tca ggt 1152
Ala Gly Arg Gly Phe Ser Asp Val Phe Glu Glu Glu Ile Thr Ser Gly 370
375 380 ggc ttt tgt gga ggg aac ccg agg tca tat caa caa tgg gtg cat
aca 1200 Gly Phe Cys Gly Gly Asn Pro Arg Ser Tyr Gln Gln Trp Val
His Thr 385 390 395 400 gtc aag aaa gga ggt gca ctg ttc aac aca gca
atg acc aaa gca acc 1248 Val Lys Lys Gly Gly Ala Leu Phe Asn Thr
Ala Met Thr Lys Ala Thr 405 410 415 cct gct gta cgg aca gca tat aaa
ttt gca aaa aat cat gca aag ctg 1296 Pro Ala Val Arg Thr Ala Tyr
Lys Phe Ala Lys Asn His Ala Lys Leu 420 425 430 gga cta aag gaa gtg
aag agt aaa cta aaa cac aag gaa aat gaa gaa 1344 Gly Leu Lys Glu
Val Lys Ser Lys Leu Lys His Lys Glu Asn Glu Glu 435 440 445 gat tat
ggg acc tgt tct agt tct gta caa tat aca cca gtt tac aaa 1392 Asp
Tyr Gly Thr Cys Ser Ser Ser Val Gln Tyr Thr Pro Val Tyr Lys 450 455
460 tta cac aat gaa aag gga gga aac tca gaa aag cgt aag ctt gct cag
1440 Leu His Asn Glu Lys Gly Gly Asn Ser Glu Lys Arg Lys Leu Ala
Gln 465 470 475 480 gca cgc tta aaa agg cct ctt aag agc ctt gat ggt
gct cta tat gat 1488 Ala Arg Leu Lys Arg Pro Leu Lys Ser Leu Asp
Gly Ala Leu Tyr Asp 485 490 495 gat gaa gat gat gat gac att gaa aga
gca agc aag tta tct tct gaa 1536 Asp Glu Asp Asp Asp Asp Ile Glu
Arg Ala Ser Lys Leu Ser Ser Glu 500 505 510 gat ggt gaa gaa gct tct
gct tat ctc tat gag agt gat gac tct gtt 1584 Asp Gly Glu Glu Ala
Ser Ala Tyr Leu Tyr Glu Ser Asp Asp Ser Val 515 520 525 gaa aca aga
gtg aag act cct tac tca ggt gaa atg gac tta cta gga 1632 Glu Thr
Arg Val Lys Thr Pro Tyr Ser Gly Glu Met Asp Leu Leu Gly 530 535 540
gag att ctt gat aca ttg agc aca cac agc tca gat cag ggg agg ctg
1680 Glu Ile Leu Asp Thr Leu Ser Thr His Ser Ser Asp Gln Gly Arg
Leu 545 550 555 560 gca gct gca aag agc ttg gat ttc ttt aga tca atg
gac gac att gat 1728 Ala Ala Ala Lys Ser Leu Asp Phe Phe Arg Ser
Met Asp Asp Ile Asp 565 570 575 tac aaa cct acg aat aaa tct aat gct
cct agt gag aat aac ctg gct 1776 Tyr Lys Pro Thr Asn Lys Ser Asn
Ala Pro Ser Glu Asn Asn Leu Ala 580 585 590 ttc ctc tgt ggt ggt tct
ggt gac caa gca gag tgg aat ctt ggg caa 1824 Phe Leu Cys Gly Gly
Ser Gly Asp Gln Ala Glu Trp Asn Leu Gly Gln 595 600 605 gac gat agt
gcc ctc cat ggc aaa cac ctc cct cca tct cct agg aag 1872 Asp Asp
Ser Ala Leu His Gly Lys His Leu Pro Pro Ser Pro Arg Lys 610 615 620
cgg gtt tcc tct agt ggt ttg aca gat tct ctg ttt atc ctg aaa gag
1920 Arg Val Ser Ser Ser Gly Leu Thr Asp Ser Leu Phe Ile Leu Lys
Glu 625 630 635 640 gaa aac agt aac aag cac ctc ggt gct gac aat gtg
agt gac cct act 1968 Glu Asn Ser Asn Lys His Leu Gly Ala Asp Asn
Val Ser Asp Pro Thr 645 650 655 tca gga ctg gat ttc caa ctc act tcc
cct gaa gtt tcc cag act gat 2016 Ser Gly Leu Asp Phe Gln Leu Thr
Ser Pro Glu Val Ser Gln Thr Asp 660 665 670 aaa gga aaa aca gaa aag
agg gaa aca cta agc cag att tca gat gat 2064 Lys Gly Lys Thr Glu
Lys Arg Glu Thr Leu Ser Gln Ile Ser Asp Asp 675 680 685 ctg ctt ata
ccc ggt ctt ggg cgg cat tca tcg act ttt gtt cct tgg 2112 Leu Leu
Ile Pro Gly Leu Gly Arg His Ser Ser Thr Phe Val Pro Trp 690 695 700
gag aaa gaa ggg aaa gaa gcc aaa gag act tca gaa gat att gga ctg
2160 Glu Lys Glu Gly Lys Glu Ala Lys Glu Thr Ser Glu Asp Ile Gly
Leu 705 710 715 720 ctc cat gaa gta gtg tca tta tgt cat atg aca tct
gac ttc caa caa 2208 Leu His Glu Val Val Ser Leu Cys His Met Thr
Ser Asp Phe Gln Gln 725 730 735 agc ttg aac att tca gac aaa aac aca
aat gga aac caa act aga tct 2256 Ser Leu Asn Ile Ser Asp Lys Asn
Thr Asn Gly Asn Gln Thr Arg Ser 740 745 750 64 752 PRT Homo sapiens
64 Arg Ser Asp Pro Val Val Leu Trp Lys Phe Pro Glu Asp Phe Gly Asp
1 5 10 15 Gln Glu Ile Leu Gln Ser Val Pro Lys Phe Cys Phe Pro Phe
Asp Val 20 25 30 Glu Arg Val Ser Gln Asn Gln Val Gly Gln His Phe
Thr Phe Val Leu 35 40 45 Thr Asp Ile Glu Ser Lys Gln Arg Phe Gly
Phe Cys Arg Leu Thr Ser 50 55 60 Gly Gly Thr Ile Cys Leu Cys Ile
Leu Ser Tyr Leu Pro Trp Phe Glu 65 70 75 80 Val Tyr Tyr Lys Leu Leu
Asn Thr Leu Ala Asp Tyr Leu Ala Lys Glu 85 90 95 Leu Glu Asn Asp
Leu Asn Glu Thr Leu Arg Ser Leu Tyr Asn His Pro 100 105 110 Val Pro
Lys Ala Asn Thr Pro Val Asn Leu Ser Val Asn Gln Glu Ile 115 120 125
Phe Ile Thr Cys Glu Gln Val Leu Lys Asp Gln Pro Ala Leu Leu Pro 130
135 140 His Ser Tyr Phe Ile Ala Pro Asp Val Thr Gly Leu Pro Thr Ile
Pro 145 150 155 160 Glu Ser Arg Asn Leu Thr Glu Tyr Phe Val Ala Val
Asp Val Asn Asn 165 170 175 Met Leu Gln Leu Tyr Ala Ser Met Leu His
Glu Arg Arg Ile Val Ile 180 185 190 Ile Ser Ser Lys Leu Ser Thr Leu
Thr Ala Cys Ile His Gly Ser Ala 195 200 205 Ala Leu Leu Tyr Pro Met
Tyr Trp Gln His Ile Tyr Ile Pro Val Leu 210 215 220 Pro Pro His Leu
Leu Asp Tyr Cys Cys Ala Pro Met Pro Tyr Leu Ile 225 230 235 240 Gly
Ile His Ser Ser Leu Ile Glu Arg Val Lys Asn Lys Ser Leu Glu 245 250
255 Asp Val Val Met Leu Asn Val Asp Thr Asn Thr Leu Glu Ser Pro Phe
260 265 270 Ser Asp Leu Asn Asn Leu Pro Ser Asp Val Val Ser Ala Leu
Lys Asn 275 280 285 Lys Leu Lys Lys Gln Ser Thr Ala Thr Gly Asp Gly
Val Ala Arg Ala 290 295 300 Phe Leu Arg Ala Gln Ala Ala Leu Phe Gly
Ser Tyr Arg Asp Ala Leu 305 310 315 320 Arg Tyr Lys Pro Gly Glu Pro
Ile Thr Phe Cys Glu Glu Ser Phe Val 325 330 335 Lys His Arg Ser Ser
Val Met Lys Gln Phe Leu Glu Thr Ala Ile Asn 340 345 350 Leu Gln Leu
Phe Lys Gln Phe Ile Asp Gly Arg Leu Ala Lys Leu Asn 355 360 365 Ala
Gly Arg Gly Phe Ser Asp Val Phe Glu Glu Glu Ile Thr Ser Gly 370 375
380 Gly Phe Cys Gly Gly Asn Pro Arg Ser Tyr Gln Gln Trp Val His Thr
385 390 395 400 Val Lys Lys Gly Gly Ala Leu Phe Asn Thr Ala Met Thr
Lys Ala Thr 405 410 415 Pro Ala Val Arg Thr Ala Tyr Lys Phe Ala Lys
Asn His Ala Lys Leu 420 425 430 Gly Leu Lys Glu Val Lys Ser Lys Leu
Lys His Lys Glu Asn Glu Glu 435 440 445 Asp Tyr Gly Thr Cys Ser Ser
Ser Val Gln Tyr Thr Pro Val Tyr Lys 450 455 460 Leu His Asn Glu Lys
Gly Gly Asn Ser Glu Lys Arg Lys Leu Ala Gln 465 470 475 480 Ala Arg
Leu Lys Arg Pro Leu Lys Ser Leu Asp Gly Ala Leu Tyr Asp 485 490 495
Asp Glu Asp Asp Asp Asp Ile Glu Arg Ala Ser Lys Leu Ser Ser Glu 500
505 510 Asp Gly Glu Glu Ala Ser Ala Tyr Leu Tyr Glu Ser Asp Asp Ser
Val 515 520 525 Glu Thr Arg Val Lys Thr Pro Tyr Ser Gly Glu Met Asp
Leu Leu Gly 530 535 540 Glu Ile Leu Asp Thr Leu Ser Thr His Ser Ser
Asp Gln Gly Arg Leu 545 550 555 560 Ala Ala Ala Lys Ser Leu Asp Phe
Phe Arg Ser Met Asp Asp Ile Asp 565 570 575 Tyr Lys Pro Thr Asn Lys
Ser Asn Ala Pro Ser Glu Asn Asn Leu Ala 580 585 590 Phe Leu Cys Gly
Gly Ser Gly Asp Gln Ala Glu Trp Asn Leu Gly Gln 595 600 605 Asp Asp
Ser Ala Leu His Gly Lys His Leu Pro Pro Ser Pro Arg Lys 610 615 620
Arg Val Ser Ser Ser Gly Leu Thr Asp Ser Leu Phe Ile Leu Lys Glu 625
630 635 640 Glu Asn Ser Asn Lys His Leu Gly Ala Asp Asn Val Ser Asp
Pro Thr 645 650 655 Ser Gly Leu Asp Phe Gln Leu Thr Ser Pro Glu Val
Ser Gln Thr Asp 660 665 670 Lys Gly Lys Thr Glu Lys Arg Glu Thr Leu
Ser Gln Ile Ser Asp Asp 675 680 685 Leu Leu Ile Pro Gly Leu Gly Arg
His Ser Ser Thr Phe Val Pro Trp 690 695 700 Glu Lys Glu Gly Lys Glu
Ala Lys Glu Thr Ser Glu Asp Ile Gly Leu 705 710 715 720 Leu His Glu
Val Val Ser Leu Cys His Met Thr Ser Asp Phe Gln Gln 725 730 735 Ser
Leu Asn Ile Ser Asp Lys Asn Thr Asn Gly Asn Gln Thr Arg Ser 740 745
750 65 2259 DNA Homo sapiens CDS (1)..(2259) 65 aga tct gat cct gtg
gta ttg tgg aaa ttc cca gag gac ttt gga gac 48 Arg Ser Asp Pro Val
Val Leu Trp Lys Phe Pro Glu Asp Phe Gly Asp 1 5 10 15 cag gaa ata
cta cag agt gtg cca aag ttc tgt ttt ccc ttt gac gtt 96 Gln Glu Ile
Leu Gln Ser Val Pro Lys Phe Cys Phe Pro Phe Asp Val 20 25 30 gaa
agg gtg tct cag aat caa gtt gga cag cac ttt acc ttt gta ctg 144 Glu
Arg Val Ser Gln Asn Gln Val Gly Gln His Phe Thr Phe Val Leu 35 40
45 aca gac att gaa agt aaa cag
aga ttt gga ttc tgc aga ctg acg tca 192 Thr Asp Ile Glu Ser Lys Gln
Arg Phe Gly Phe Cys Arg Leu Thr Ser 50 55 60 gga ggc aca att tgt
tta tgc atc ctt agt tac ctt ccc tgg ttt gaa 240 Gly Gly Thr Ile Cys
Leu Cys Ile Leu Ser Tyr Leu Pro Trp Phe Glu 65 70 75 80 gtg tat tac
aag ctt cta aat act ctt gca gat tac ttg gct aag gaa 288 Val Tyr Tyr
Lys Leu Leu Asn Thr Leu Ala Asp Tyr Leu Ala Lys Glu 85 90 95 ctg
gaa aat gat ttg aat gaa act ctc aga tca ctg tat aac cac cca 336 Leu
Glu Asn Asp Leu Asn Glu Thr Leu Arg Ser Leu Tyr Asn His Pro 100 105
110 gta cca aag gca aat act cct gta aat ttg agt gtg aac caa gag ata
384 Val Pro Lys Ala Asn Thr Pro Val Asn Leu Ser Val Asn Gln Glu Ile
115 120 125 ttt att gcc tgt gag caa gtt ctg aaa gat cag cct gct cta
gta ccg 432 Phe Ile Ala Cys Glu Gln Val Leu Lys Asp Gln Pro Ala Leu
Val Pro 130 135 140 cat tcc tac ttc att gcc cct gat gta act gga ctc
cca aca ata ccc 480 His Ser Tyr Phe Ile Ala Pro Asp Val Thr Gly Leu
Pro Thr Ile Pro 145 150 155 160 gag agt aga aat ctt aca gaa tat ttt
gtt gcc gtg gat gtg aac aac 528 Glu Ser Arg Asn Leu Thr Glu Tyr Phe
Val Ala Val Asp Val Asn Asn 165 170 175 atg ctg cag ctg tat gcc agt
atg ctg cat gaa agg cgc atc gtg att 576 Met Leu Gln Leu Tyr Ala Ser
Met Leu His Glu Arg Arg Ile Val Ile 180 185 190 atc tcg agc aaa tta
agc act tta act gcc tgt atc cat gga tca gct 624 Ile Ser Ser Lys Leu
Ser Thr Leu Thr Ala Cys Ile His Gly Ser Ala 195 200 205 gct ctt cta
tac cca atg tat tgg caa cac ata tac atc cca gtg ctt 672 Ala Leu Leu
Tyr Pro Met Tyr Trp Gln His Ile Tyr Ile Pro Val Leu 210 215 220 cct
cca cac ctg ctg gac tac tgc tgt gcc cca atg cca tac ctg att 720 Pro
Pro His Leu Leu Asp Tyr Cys Cys Ala Pro Met Pro Tyr Leu Ile 225 230
235 240 gga ata cac tcc agc ctc ata gag aga gtg aaa aac aaa tca ttg
gaa 768 Gly Ile His Ser Ser Leu Ile Glu Arg Val Lys Asn Lys Ser Leu
Glu 245 250 255 gat gtt gtt atg tta aat gtt gat aca aac aca tta gaa
tca cca ttt 816 Asp Val Val Met Leu Asn Val Asp Thr Asn Thr Leu Glu
Ser Pro Phe 260 265 270 agt gac ttg aac aac cta cca agt gat gtg gtc
tcg gcc ttg aaa aat 864 Ser Asp Leu Asn Asn Leu Pro Ser Asp Val Val
Ser Ala Leu Lys Asn 275 280 285 aaa ctg aag aag cag tct aca gct acg
ggt gat gga gta gct agg gcc 912 Lys Leu Lys Lys Gln Ser Thr Ala Thr
Gly Asp Gly Val Ala Arg Ala 290 295 300 ttt ctt aga gca cag gct gct
ttg ttt gga tcc tac aga gat gca ctg 960 Phe Leu Arg Ala Gln Ala Ala
Leu Phe Gly Ser Tyr Arg Asp Ala Leu 305 310 315 320 aga tac aaa cct
ggt gag ccc atc act ttc tgt gag gag agt ttt gta 1008 Arg Tyr Lys
Pro Gly Glu Pro Ile Thr Phe Cys Glu Glu Ser Phe Val 325 330 335 aag
cac cgc tca agc gtg atg aaa cag ttc ctg gaa act gcc att aac 1056
Lys His Arg Ser Ser Val Met Lys Gln Phe Leu Glu Thr Ala Ile Asn 340
345 350 ctc cag ctt ttt aag cag ttt atc gat ggt cga ctg gca aaa cta
aat 1104 Leu Gln Leu Phe Lys Gln Phe Ile Asp Gly Arg Leu Ala Lys
Leu Asn 355 360 365 gca gga agg ggt ttc tct gat gta ttt gaa gaa gag
atc act tca ggt 1152 Ala Gly Arg Gly Phe Ser Asp Val Phe Glu Glu
Glu Ile Thr Ser Gly 370 375 380 ggc ttt tgt gga ggg aac ccg agg tca
tat caa caa tgg gtg cat aca 1200 Gly Phe Cys Gly Gly Asn Pro Arg
Ser Tyr Gln Gln Trp Val His Thr 385 390 395 400 gtc aag aaa gga ggt
gca ctg ttc aac aca gca atg acc aaa gca acc 1248 Val Lys Lys Gly
Gly Ala Leu Phe Asn Thr Ala Met Thr Lys Ala Thr 405 410 415 cct gct
gta cgg aca gca tat aaa ttt gca aaa aat cat gca aag ctg 1296 Pro
Ala Val Arg Thr Ala Tyr Lys Phe Ala Lys Asn His Ala Lys Leu 420 425
430 gga cta aag gaa gtg aag agt aaa cta aaa cac aag gaa aat gaa gaa
1344 Gly Leu Lys Glu Val Lys Ser Lys Leu Lys His Lys Glu Asn Glu
Glu 435 440 445 gat tat ggg acc tgt tct agt tct gta caa tat aca cca
gtt tac aaa 1392 Asp Tyr Gly Thr Cys Ser Ser Ser Val Gln Tyr Thr
Pro Val Tyr Lys 450 455 460 tta cac aat gaa aag gga gga aac tca gaa
aag cgt aag ctt gct cag 1440 Leu His Asn Glu Lys Gly Gly Asn Ser
Glu Lys Arg Lys Leu Ala Gln 465 470 475 480 gca cgc tta aaa agg cct
ctt aag agc ctt gat ggt gct cta tat gat 1488 Ala Arg Leu Lys Arg
Pro Leu Lys Ser Leu Asp Gly Ala Leu Tyr Asp 485 490 495 gat gaa gat
gat gat gac att gaa aga gca agc aag tta tct tct gaa 1536 Asp Glu
Asp Asp Asp Asp Ile Glu Arg Ala Ser Lys Leu Ser Ser Glu 500 505 510
gat ggt gaa gaa gct tct gct tat ctc tat gag agt gat gac tct gtt
1584 Asp Gly Glu Glu Ala Ser Ala Tyr Leu Tyr Glu Ser Asp Asp Ser
Val 515 520 525 gaa aca aga gtg aag act cct tac tca ggt gaa atg gac
tta cta gga 1632 Glu Thr Arg Val Lys Thr Pro Tyr Ser Gly Glu Met
Asp Leu Leu Gly 530 535 540 gag att ctt gat aca ttg agc aca cac agc
tca gat cag ggg aag ctg 1680 Glu Ile Leu Asp Thr Leu Ser Thr His
Ser Ser Asp Gln Gly Lys Leu 545 550 555 560 gca gct gca aag agc ttg
gat ttc ttt aga tca atg gat gac att gat 1728 Ala Ala Ala Lys Ser
Leu Asp Phe Phe Arg Ser Met Asp Asp Ile Asp 565 570 575 tac aaa cct
acg aat aaa tct aat gct cct agt gag aat aac ctg gct 1776 Tyr Lys
Pro Thr Asn Lys Ser Asn Ala Pro Ser Glu Asn Asn Leu Ala 580 585 590
ttc ctc tgt agt ggt tct ggt gac caa gca gag tgg aat ctt ggg caa
1824 Phe Leu Cys Ser Gly Ser Gly Asp Gln Ala Glu Trp Asn Leu Gly
Gln 595 600 605 gac gat agt gcc ctc cat ggc aaa cac ctc cct cca tct
cct agg aag 1872 Asp Asp Ser Ala Leu His Gly Lys His Leu Pro Pro
Ser Pro Arg Lys 610 615 620 cgg gtt tcc tct agt ggt ttg aca gat tct
ctg tct atc ctg aaa gag 1920 Arg Val Ser Ser Ser Gly Leu Thr Asp
Ser Leu Ser Ile Leu Lys Glu 625 630 635 640 gaa aac agt aac aag cac
ctc ggt gct gac aat gtg agt gac cct act 1968 Glu Asn Ser Asn Lys
His Leu Gly Ala Asp Asn Val Ser Asp Pro Thr 645 650 655 tca gga ctg
gat ttc caa ctc act tcc cct gaa gtt tcc cag act gat 2016 Ser Gly
Leu Asp Phe Gln Leu Thr Ser Pro Glu Val Ser Gln Thr Asp 660 665 670
aaa gga aaa aca gaa aag agg gaa aca cta agc cag att tca gat gat
2064 Lys Gly Lys Thr Glu Lys Arg Glu Thr Leu Ser Gln Ile Ser Asp
Asp 675 680 685 ctg ctt ata ccc ggt ctt ggg cgg cat tca tcg act ttt
gtt cct tgg 2112 Leu Leu Ile Pro Gly Leu Gly Arg His Ser Ser Thr
Phe Val Pro Trp 690 695 700 gag aaa gaa ggg aaa gaa gcc aaa gag act
tca gaa gat att gga ctg 2160 Glu Lys Glu Gly Lys Glu Ala Lys Glu
Thr Ser Glu Asp Ile Gly Leu 705 710 715 720 ctc cat gaa gta gtg tca
tta tgt cat atg aca tct gac ttc caa gct 2208 Leu His Glu Val Val
Ser Leu Cys His Met Thr Ser Asp Phe Gln Ala 725 730 735 aaa gct tgg
aac att tca gac aaa aac aca aat gga aac caa act aga 2256 Lys Ala
Trp Asn Ile Ser Asp Lys Asn Thr Asn Gly Asn Gln Thr Arg 740 745 750
tct 2259 Ser 66 753 PRT Homo sapiens 66 Arg Ser Asp Pro Val Val Leu
Trp Lys Phe Pro Glu Asp Phe Gly Asp 1 5 10 15 Gln Glu Ile Leu Gln
Ser Val Pro Lys Phe Cys Phe Pro Phe Asp Val 20 25 30 Glu Arg Val
Ser Gln Asn Gln Val Gly Gln His Phe Thr Phe Val Leu 35 40 45 Thr
Asp Ile Glu Ser Lys Gln Arg Phe Gly Phe Cys Arg Leu Thr Ser 50 55
60 Gly Gly Thr Ile Cys Leu Cys Ile Leu Ser Tyr Leu Pro Trp Phe Glu
65 70 75 80 Val Tyr Tyr Lys Leu Leu Asn Thr Leu Ala Asp Tyr Leu Ala
Lys Glu 85 90 95 Leu Glu Asn Asp Leu Asn Glu Thr Leu Arg Ser Leu
Tyr Asn His Pro 100 105 110 Val Pro Lys Ala Asn Thr Pro Val Asn Leu
Ser Val Asn Gln Glu Ile 115 120 125 Phe Ile Ala Cys Glu Gln Val Leu
Lys Asp Gln Pro Ala Leu Val Pro 130 135 140 His Ser Tyr Phe Ile Ala
Pro Asp Val Thr Gly Leu Pro Thr Ile Pro 145 150 155 160 Glu Ser Arg
Asn Leu Thr Glu Tyr Phe Val Ala Val Asp Val Asn Asn 165 170 175 Met
Leu Gln Leu Tyr Ala Ser Met Leu His Glu Arg Arg Ile Val Ile 180 185
190 Ile Ser Ser Lys Leu Ser Thr Leu Thr Ala Cys Ile His Gly Ser Ala
195 200 205 Ala Leu Leu Tyr Pro Met Tyr Trp Gln His Ile Tyr Ile Pro
Val Leu 210 215 220 Pro Pro His Leu Leu Asp Tyr Cys Cys Ala Pro Met
Pro Tyr Leu Ile 225 230 235 240 Gly Ile His Ser Ser Leu Ile Glu Arg
Val Lys Asn Lys Ser Leu Glu 245 250 255 Asp Val Val Met Leu Asn Val
Asp Thr Asn Thr Leu Glu Ser Pro Phe 260 265 270 Ser Asp Leu Asn Asn
Leu Pro Ser Asp Val Val Ser Ala Leu Lys Asn 275 280 285 Lys Leu Lys
Lys Gln Ser Thr Ala Thr Gly Asp Gly Val Ala Arg Ala 290 295 300 Phe
Leu Arg Ala Gln Ala Ala Leu Phe Gly Ser Tyr Arg Asp Ala Leu 305 310
315 320 Arg Tyr Lys Pro Gly Glu Pro Ile Thr Phe Cys Glu Glu Ser Phe
Val 325 330 335 Lys His Arg Ser Ser Val Met Lys Gln Phe Leu Glu Thr
Ala Ile Asn 340 345 350 Leu Gln Leu Phe Lys Gln Phe Ile Asp Gly Arg
Leu Ala Lys Leu Asn 355 360 365 Ala Gly Arg Gly Phe Ser Asp Val Phe
Glu Glu Glu Ile Thr Ser Gly 370 375 380 Gly Phe Cys Gly Gly Asn Pro
Arg Ser Tyr Gln Gln Trp Val His Thr 385 390 395 400 Val Lys Lys Gly
Gly Ala Leu Phe Asn Thr Ala Met Thr Lys Ala Thr 405 410 415 Pro Ala
Val Arg Thr Ala Tyr Lys Phe Ala Lys Asn His Ala Lys Leu 420 425 430
Gly Leu Lys Glu Val Lys Ser Lys Leu Lys His Lys Glu Asn Glu Glu 435
440 445 Asp Tyr Gly Thr Cys Ser Ser Ser Val Gln Tyr Thr Pro Val Tyr
Lys 450 455 460 Leu His Asn Glu Lys Gly Gly Asn Ser Glu Lys Arg Lys
Leu Ala Gln 465 470 475 480 Ala Arg Leu Lys Arg Pro Leu Lys Ser Leu
Asp Gly Ala Leu Tyr Asp 485 490 495 Asp Glu Asp Asp Asp Asp Ile Glu
Arg Ala Ser Lys Leu Ser Ser Glu 500 505 510 Asp Gly Glu Glu Ala Ser
Ala Tyr Leu Tyr Glu Ser Asp Asp Ser Val 515 520 525 Glu Thr Arg Val
Lys Thr Pro Tyr Ser Gly Glu Met Asp Leu Leu Gly 530 535 540 Glu Ile
Leu Asp Thr Leu Ser Thr His Ser Ser Asp Gln Gly Lys Leu 545 550 555
560 Ala Ala Ala Lys Ser Leu Asp Phe Phe Arg Ser Met Asp Asp Ile Asp
565 570 575 Tyr Lys Pro Thr Asn Lys Ser Asn Ala Pro Ser Glu Asn Asn
Leu Ala 580 585 590 Phe Leu Cys Ser Gly Ser Gly Asp Gln Ala Glu Trp
Asn Leu Gly Gln 595 600 605 Asp Asp Ser Ala Leu His Gly Lys His Leu
Pro Pro Ser Pro Arg Lys 610 615 620 Arg Val Ser Ser Ser Gly Leu Thr
Asp Ser Leu Ser Ile Leu Lys Glu 625 630 635 640 Glu Asn Ser Asn Lys
His Leu Gly Ala Asp Asn Val Ser Asp Pro Thr 645 650 655 Ser Gly Leu
Asp Phe Gln Leu Thr Ser Pro Glu Val Ser Gln Thr Asp 660 665 670 Lys
Gly Lys Thr Glu Lys Arg Glu Thr Leu Ser Gln Ile Ser Asp Asp 675 680
685 Leu Leu Ile Pro Gly Leu Gly Arg His Ser Ser Thr Phe Val Pro Trp
690 695 700 Glu Lys Glu Gly Lys Glu Ala Lys Glu Thr Ser Glu Asp Ile
Gly Leu 705 710 715 720 Leu His Glu Val Val Ser Leu Cys His Met Thr
Ser Asp Phe Gln Ala 725 730 735 Lys Ala Trp Asn Ile Ser Asp Lys Asn
Thr Asn Gly Asn Gln Thr Arg 740 745 750 Ser 67 2256 DNA Homo
sapiens CDS (1)..(2256) 67 aga tct gat cct gtg gta ttg tgg aaa ttc
cca gag gac ttt gga gac 48 Arg Ser Asp Pro Val Val Leu Trp Lys Phe
Pro Glu Asp Phe Gly Asp 1 5 10 15 cag gaa ata cta cag agt gtg cca
aag ttc tgt ttt ccc ttt gac gtt 96 Gln Glu Ile Leu Gln Ser Val Pro
Lys Phe Cys Phe Pro Phe Asp Val 20 25 30 gaa agg gtg tct cag aat
caa gtt gga cag cac ttt acc ttt gta ctg 144 Glu Arg Val Ser Gln Asn
Gln Val Gly Gln His Phe Thr Phe Val Leu 35 40 45 aca gac att gaa
agt aaa cag aga ttt gga ttc tgc aga ctg acg tca 192 Thr Asp Ile Glu
Ser Lys Gln Arg Phe Gly Phe Cys Arg Leu Thr Ser 50 55 60 gga ggc
aca att tgt tta tgc atc ctt agt tac ctt ccc tgg ttt gaa 240 Gly Gly
Thr Ile Cys Leu Cys Ile Leu Ser Tyr Leu Pro Trp Phe Glu 65 70 75 80
gtg tat tac aag ctt cta aat act ctt gca gat tac ttg gct aag gaa 288
Val Tyr Tyr Lys Leu Leu Asn Thr Leu Ala Asp Tyr Leu Ala Lys Glu 85
90 95 ctg gaa aat gat ttg aat gaa act ctc aga tca ctg tat aac cac
cca 336 Leu Glu Asn Asp Leu Asn Glu Thr Leu Arg Ser Leu Tyr Asn His
Pro 100 105 110 gta cca aag gca aat act cct gta aat ttg agt gtg aac
caa gag ata 384 Val Pro Lys Ala Asn Thr Pro Val Asn Leu Ser Val Asn
Gln Glu Ile 115 120 125 ttt att gcc tgt gag caa gtt ctg aaa gat cag
cct gct cta gta ccg 432 Phe Ile Ala Cys Glu Gln Val Leu Lys Asp Gln
Pro Ala Leu Val Pro 130 135 140 cat tcc tac ttc att gcc cct gat gta
act gga ctc cca aca ata ccc 480 His Ser Tyr Phe Ile Ala Pro Asp Val
Thr Gly Leu Pro Thr Ile Pro 145 150 155 160 gag agt aga aat ctt aca
gaa tat ttt gtt gcc gtg gat gtg aac aac 528 Glu Ser Arg Asn Leu Thr
Glu Tyr Phe Val Ala Val Asp Val Asn Asn 165 170 175 atg ctg cag ctg
tat gcc agt atg ctg cat gaa agg cgc atc gtg att 576 Met Leu Gln Leu
Tyr Ala Ser Met Leu His Glu Arg Arg Ile Val Ile 180 185 190 atc tcg
agc aaa tta agc act tta act gcc tgt atc cat gga tca gct 624 Ile Ser
Ser Lys Leu Ser Thr Leu Thr Ala Cys Ile His Gly Ser Ala 195 200 205
gct ctt cta tac cca atg tat tgg caa cac ata tac atc cca gtg ctt 672
Ala Leu Leu Tyr Pro Met Tyr Trp Gln His Ile Tyr Ile Pro Val Leu 210
215 220 cct cca cac ctg ctg gac tac tgc tgt gcc cca atg cca tac ctg
att 720 Pro Pro His Leu Leu Asp Tyr Cys Cys Ala Pro Met Pro Tyr Leu
Ile 225 230 235 240 gga ata cac tcc agc ctc ata gag aga gtg aaa aac
aaa tca ttg gaa 768 Gly Ile His Ser Ser Leu Ile Glu Arg Val Lys Asn
Lys Ser Leu Glu 245 250 255 gat gtt gtt atg tta aat gtt gat aca aac
aca tta gaa tca cca ttt 816 Asp Val Val Met Leu Asn Val Asp Thr Asn
Thr Leu Glu Ser Pro Phe 260 265 270 agt gac ttg aac aac cta cca agt
gat gtg gtc tcg gcc ttg aaa aat 864 Ser Asp Leu Asn Asn Leu Pro Ser
Asp Val Val Ser Ala Leu Lys Asn 275 280 285 aaa ctg aag aag cag tct
aca gct acg ggt gat gga gta gct agg gcc 912 Lys Leu Lys Lys Gln Ser
Thr Ala Thr Gly Asp Gly Val Ala Arg Ala 290 295 300 ttt ctt aga gca
cag gct gct ttg ttt gga tcc tac aga gat gca ctg 960 Phe Leu Arg Ala
Gln Ala Ala Leu Phe Gly Ser Tyr Arg Asp Ala Leu 305 310 315 320 aga
tac aaa cct ggt gag ccc atc act ttc tgt gag gag agt ttt gta 1008
Arg Tyr Lys Pro Gly Glu Pro Ile Thr Phe Cys Glu Glu Ser Phe Val 325
330 335 aag cac cgc tca agc gtg atg aaa cag ttc ctg gaa
act gcc att aac 1056 Lys His Arg Ser Ser Val Met Lys Gln Phe Leu
Glu Thr Ala Ile Asn 340 345 350 ctc cag ctt ttt aag cag ttt atc gat
ggt cga ctg gca aaa cta aat 1104 Leu Gln Leu Phe Lys Gln Phe Ile
Asp Gly Arg Leu Ala Lys Leu Asn 355 360 365 gca gga agg ggt ttc tct
gat gta ttt gaa gaa gag atc act tca ggt 1152 Ala Gly Arg Gly Phe
Ser Asp Val Phe Glu Glu Glu Ile Thr Ser Gly 370 375 380 ggc ttt tgt
gga ggg aac ccg agg tca tat caa caa tgg gtg cat aca 1200 Gly Phe
Cys Gly Gly Asn Pro Arg Ser Tyr Gln Gln Trp Val His Thr 385 390 395
400 gtc aag aaa gga ggt gca ctg ttc aac aca gca atg acc aaa gca acc
1248 Val Lys Lys Gly Gly Ala Leu Phe Asn Thr Ala Met Thr Lys Ala
Thr 405 410 415 cct gct gta cgg aca gca tat aaa ttt gca aaa aat cat
gca aag ctg 1296 Pro Ala Val Arg Thr Ala Tyr Lys Phe Ala Lys Asn
His Ala Lys Leu 420 425 430 gga cta aag gaa gtg aag agt aaa cta aaa
cac aag gaa aat gaa gaa 1344 Gly Leu Lys Glu Val Lys Ser Lys Leu
Lys His Lys Glu Asn Glu Glu 435 440 445 gat tat ggg acc tgt tct agt
tct gta caa tat aca cca gtt tac aaa 1392 Asp Tyr Gly Thr Cys Ser
Ser Ser Val Gln Tyr Thr Pro Val Tyr Lys 450 455 460 tta cac aat gaa
aag gga gga aac tca gaa aag cgt aag ctt gct cag 1440 Leu His Asn
Glu Lys Gly Gly Asn Ser Glu Lys Arg Lys Leu Ala Gln 465 470 475 480
gca cgc tta aaa agg cct ctt aag agc ctt gat ggt gct cta tat gat
1488 Ala Arg Leu Lys Arg Pro Leu Lys Ser Leu Asp Gly Ala Leu Tyr
Asp 485 490 495 gat gaa gat gat gat gac att gaa aga gca agc aag tta
tct tct gaa 1536 Asp Glu Asp Asp Asp Asp Ile Glu Arg Ala Ser Lys
Leu Ser Ser Glu 500 505 510 gat ggt gaa gaa gct tct gct tat ctc tat
gag agt gat gac tct gtt 1584 Asp Gly Glu Glu Ala Ser Ala Tyr Leu
Tyr Glu Ser Asp Asp Ser Val 515 520 525 gaa aca aga gtg aag act cct
tac tca ggt gaa atg gac tta cta gga 1632 Glu Thr Arg Val Lys Thr
Pro Tyr Ser Gly Glu Met Asp Leu Leu Gly 530 535 540 gag att ctt gat
aca ttg agc aca cac agc tca gat cag ggg aag ctg 1680 Glu Ile Leu
Asp Thr Leu Ser Thr His Ser Ser Asp Gln Gly Lys Leu 545 550 555 560
gca gct gca aag agc ttg gat ttc ttt aga tca atg gat gac att gat
1728 Ala Ala Ala Lys Ser Leu Asp Phe Phe Arg Ser Met Asp Asp Ile
Asp 565 570 575 tac aaa cct acg aat aaa tct aat gct cct agt gag aat
aac ctg gct 1776 Tyr Lys Pro Thr Asn Lys Ser Asn Ala Pro Ser Glu
Asn Asn Leu Ala 580 585 590 ttc ctc tgt ggt ggt tct ggt gac caa gca
gag tgg aat ctt ggg caa 1824 Phe Leu Cys Gly Gly Ser Gly Asp Gln
Ala Glu Trp Asn Leu Gly Gln 595 600 605 gac gat agt gcc ctc cat ggc
aaa cac ctc cct cca tct cct agg aag 1872 Asp Asp Ser Ala Leu His
Gly Lys His Leu Pro Pro Ser Pro Arg Lys 610 615 620 cgg gtt tcc tct
agt ggt ttg aca gat tct ctg ttt atc ctg aaa gag 1920 Arg Val Ser
Ser Ser Gly Leu Thr Asp Ser Leu Phe Ile Leu Lys Glu 625 630 635 640
gaa aac agt aac aag cac ctc ggt gct gac aat gtg agt gac cct act
1968 Glu Asn Ser Asn Lys His Leu Gly Ala Asp Asn Val Ser Asp Pro
Thr 645 650 655 tca gga ctg gat ttc caa ctc act tcc cct gaa gtt tcc
cag act gat 2016 Ser Gly Leu Asp Phe Gln Leu Thr Ser Pro Glu Val
Ser Gln Thr Asp 660 665 670 aaa gga aaa aca gaa aag agg gaa aca cta
agc cag att tca gat gat 2064 Lys Gly Lys Thr Glu Lys Arg Glu Thr
Leu Ser Gln Ile Ser Asp Asp 675 680 685 ctg ctt ata ccc ggt ctt ggg
cgg cat tca tcg act ttt gtt cct tgg 2112 Leu Leu Ile Pro Gly Leu
Gly Arg His Ser Ser Thr Phe Val Pro Trp 690 695 700 gag aaa gaa ggg
aaa gaa gcc aaa gag act tca gaa gat att gga ctg 2160 Glu Lys Glu
Gly Lys Glu Ala Lys Glu Thr Ser Glu Asp Ile Gly Leu 705 710 715 720
ctc cat gaa gta gtg tca tta tgt cat atg aca tct gac ttc caa caa
2208 Leu His Glu Val Val Ser Leu Cys His Met Thr Ser Asp Phe Gln
Gln 725 730 735 agc ttg aac att tca gac aaa aac aca aat gga aac caa
act aga tct 2256 Ser Leu Asn Ile Ser Asp Lys Asn Thr Asn Gly Asn
Gln Thr Arg Ser 740 745 750 68 752 PRT Homo sapiens 68 Arg Ser Asp
Pro Val Val Leu Trp Lys Phe Pro Glu Asp Phe Gly Asp 1 5 10 15 Gln
Glu Ile Leu Gln Ser Val Pro Lys Phe Cys Phe Pro Phe Asp Val 20 25
30 Glu Arg Val Ser Gln Asn Gln Val Gly Gln His Phe Thr Phe Val Leu
35 40 45 Thr Asp Ile Glu Ser Lys Gln Arg Phe Gly Phe Cys Arg Leu
Thr Ser 50 55 60 Gly Gly Thr Ile Cys Leu Cys Ile Leu Ser Tyr Leu
Pro Trp Phe Glu 65 70 75 80 Val Tyr Tyr Lys Leu Leu Asn Thr Leu Ala
Asp Tyr Leu Ala Lys Glu 85 90 95 Leu Glu Asn Asp Leu Asn Glu Thr
Leu Arg Ser Leu Tyr Asn His Pro 100 105 110 Val Pro Lys Ala Asn Thr
Pro Val Asn Leu Ser Val Asn Gln Glu Ile 115 120 125 Phe Ile Ala Cys
Glu Gln Val Leu Lys Asp Gln Pro Ala Leu Val Pro 130 135 140 His Ser
Tyr Phe Ile Ala Pro Asp Val Thr Gly Leu Pro Thr Ile Pro 145 150 155
160 Glu Ser Arg Asn Leu Thr Glu Tyr Phe Val Ala Val Asp Val Asn Asn
165 170 175 Met Leu Gln Leu Tyr Ala Ser Met Leu His Glu Arg Arg Ile
Val Ile 180 185 190 Ile Ser Ser Lys Leu Ser Thr Leu Thr Ala Cys Ile
His Gly Ser Ala 195 200 205 Ala Leu Leu Tyr Pro Met Tyr Trp Gln His
Ile Tyr Ile Pro Val Leu 210 215 220 Pro Pro His Leu Leu Asp Tyr Cys
Cys Ala Pro Met Pro Tyr Leu Ile 225 230 235 240 Gly Ile His Ser Ser
Leu Ile Glu Arg Val Lys Asn Lys Ser Leu Glu 245 250 255 Asp Val Val
Met Leu Asn Val Asp Thr Asn Thr Leu Glu Ser Pro Phe 260 265 270 Ser
Asp Leu Asn Asn Leu Pro Ser Asp Val Val Ser Ala Leu Lys Asn 275 280
285 Lys Leu Lys Lys Gln Ser Thr Ala Thr Gly Asp Gly Val Ala Arg Ala
290 295 300 Phe Leu Arg Ala Gln Ala Ala Leu Phe Gly Ser Tyr Arg Asp
Ala Leu 305 310 315 320 Arg Tyr Lys Pro Gly Glu Pro Ile Thr Phe Cys
Glu Glu Ser Phe Val 325 330 335 Lys His Arg Ser Ser Val Met Lys Gln
Phe Leu Glu Thr Ala Ile Asn 340 345 350 Leu Gln Leu Phe Lys Gln Phe
Ile Asp Gly Arg Leu Ala Lys Leu Asn 355 360 365 Ala Gly Arg Gly Phe
Ser Asp Val Phe Glu Glu Glu Ile Thr Ser Gly 370 375 380 Gly Phe Cys
Gly Gly Asn Pro Arg Ser Tyr Gln Gln Trp Val His Thr 385 390 395 400
Val Lys Lys Gly Gly Ala Leu Phe Asn Thr Ala Met Thr Lys Ala Thr 405
410 415 Pro Ala Val Arg Thr Ala Tyr Lys Phe Ala Lys Asn His Ala Lys
Leu 420 425 430 Gly Leu Lys Glu Val Lys Ser Lys Leu Lys His Lys Glu
Asn Glu Glu 435 440 445 Asp Tyr Gly Thr Cys Ser Ser Ser Val Gln Tyr
Thr Pro Val Tyr Lys 450 455 460 Leu His Asn Glu Lys Gly Gly Asn Ser
Glu Lys Arg Lys Leu Ala Gln 465 470 475 480 Ala Arg Leu Lys Arg Pro
Leu Lys Ser Leu Asp Gly Ala Leu Tyr Asp 485 490 495 Asp Glu Asp Asp
Asp Asp Ile Glu Arg Ala Ser Lys Leu Ser Ser Glu 500 505 510 Asp Gly
Glu Glu Ala Ser Ala Tyr Leu Tyr Glu Ser Asp Asp Ser Val 515 520 525
Glu Thr Arg Val Lys Thr Pro Tyr Ser Gly Glu Met Asp Leu Leu Gly 530
535 540 Glu Ile Leu Asp Thr Leu Ser Thr His Ser Ser Asp Gln Gly Lys
Leu 545 550 555 560 Ala Ala Ala Lys Ser Leu Asp Phe Phe Arg Ser Met
Asp Asp Ile Asp 565 570 575 Tyr Lys Pro Thr Asn Lys Ser Asn Ala Pro
Ser Glu Asn Asn Leu Ala 580 585 590 Phe Leu Cys Gly Gly Ser Gly Asp
Gln Ala Glu Trp Asn Leu Gly Gln 595 600 605 Asp Asp Ser Ala Leu His
Gly Lys His Leu Pro Pro Ser Pro Arg Lys 610 615 620 Arg Val Ser Ser
Ser Gly Leu Thr Asp Ser Leu Phe Ile Leu Lys Glu 625 630 635 640 Glu
Asn Ser Asn Lys His Leu Gly Ala Asp Asn Val Ser Asp Pro Thr 645 650
655 Ser Gly Leu Asp Phe Gln Leu Thr Ser Pro Glu Val Ser Gln Thr Asp
660 665 670 Lys Gly Lys Thr Glu Lys Arg Glu Thr Leu Ser Gln Ile Ser
Asp Asp 675 680 685 Leu Leu Ile Pro Gly Leu Gly Arg His Ser Ser Thr
Phe Val Pro Trp 690 695 700 Glu Lys Glu Gly Lys Glu Ala Lys Glu Thr
Ser Glu Asp Ile Gly Leu 705 710 715 720 Leu His Glu Val Val Ser Leu
Cys His Met Thr Ser Asp Phe Gln Gln 725 730 735 Ser Leu Asn Ile Ser
Asp Lys Asn Thr Asn Gly Asn Gln Thr Arg Ser 740 745 750 69 1357 DNA
Homo sapiens CDS (1)..(1195) 69 atg aaa cta att acc atc ctt ttc ctc
tgc tcc agg cta cta cta agt 48 Met Lys Leu Ile Thr Ile Leu Phe Leu
Cys Ser Arg Leu Leu Leu Ser 1 5 10 15 tta acc cag gaa tca cag tcc
gag gaa att gat gac tgc aat gac aag 96 Leu Thr Gln Glu Ser Gln Ser
Glu Glu Ile Asp Asp Cys Asn Asp Lys 20 25 30 gat tta ttt aaa gct
gtg gat gct gct ctg aag aaa tat aac agt caa 144 Asp Leu Phe Lys Ala
Val Asp Ala Ala Leu Lys Lys Tyr Asn Ser Gln 35 40 45 aac caa agt
aac aac cag ttt gta ttg tac cgc aaa acc tgg cag gac 192 Asn Gln Ser
Asn Asn Gln Phe Val Leu Tyr Arg Lys Thr Trp Gln Asp 50 55 60 tgt
gag tac aag gat gct gca aaa gca gcc act gga gaa tgc aca gca 240 Cys
Glu Tyr Lys Asp Ala Ala Lys Ala Ala Thr Gly Glu Cys Thr Ala 65 70
75 80 acc gtg ggg aag agg agc agt acg aaa ttc tcc gtg gct acc cag
acc 288 Thr Val Gly Lys Arg Ser Ser Thr Lys Phe Ser Val Ala Thr Gln
Thr 85 90 95 tgc cag att act cca gcc gag ggc cct gtg gtg aca gcc
cag tac gac 336 Cys Gln Ile Thr Pro Ala Glu Gly Pro Val Val Thr Ala
Gln Tyr Asp 100 105 110 tgc ctc ggc tgt gtg cat cct ata tca acg cag
agc cca gac ctg gag 384 Cys Leu Gly Cys Val His Pro Ile Ser Thr Gln
Ser Pro Asp Leu Glu 115 120 125 ccc att ctg aga cac ggc att cag tac
ttt aac aac aac act caa cat 432 Pro Ile Leu Arg His Gly Ile Gln Tyr
Phe Asn Asn Asn Thr Gln His 130 135 140 tcc tcc ctc ttc acg ctt aat
gaa gta aaa cgg gcc caa aga cag gtg 480 Ser Ser Leu Phe Thr Leu Asn
Glu Val Lys Arg Ala Gln Arg Gln Val 145 150 155 160 gtg gct gga ttg
aac ttt cga att acc tac tca att gtg caa acg aat 528 Val Ala Gly Leu
Asn Phe Arg Ile Thr Tyr Ser Ile Val Gln Thr Asn 165 170 175 tgt tcc
aaa gag aat ttt ctg ttc tta act cca gac tgc aag tcc ctt 576 Cys Ser
Lys Glu Asn Phe Leu Phe Leu Thr Pro Asp Cys Lys Ser Leu 180 185 190
tgg aat ggt gat acc ggt gaa tgt aca gat aat gca tac atc gat att 624
Trp Asn Gly Asp Thr Gly Glu Cys Thr Asp Asn Ala Tyr Ile Asp Ile 195
200 205 cag cta cga att gct tcc ttc tca cag aac tgt gac att tat cca
ggg 672 Gln Leu Arg Ile Ala Ser Phe Ser Gln Asn Cys Asp Ile Tyr Pro
Gly 210 215 220 aag gat ttt gta caa cca cct acc aag att tgc gtg ggc
tgc ccc aga 720 Lys Asp Phe Val Gln Pro Pro Thr Lys Ile Cys Val Gly
Cys Pro Arg 225 230 235 240 gat ata ccc acc aac agc cca gag ctg gag
gag aca ctg act cac acc 768 Asp Ile Pro Thr Asn Ser Pro Glu Leu Glu
Glu Thr Leu Thr His Thr 245 250 255 atc aca aag ctt aat gca gag aat
aac gca act ttc tat ttc aag att 816 Ile Thr Lys Leu Asn Ala Glu Asn
Asn Ala Thr Phe Tyr Phe Lys Ile 260 265 270 gac aat gtg aaa aaa gca
aga gta cag gtg gtg gct ggc aag aaa tat 864 Asp Asn Val Lys Lys Ala
Arg Val Gln Val Val Ala Gly Lys Lys Tyr 275 280 285 ttt att gac ttc
gtg gcc agg gaa acc aca tgt tcc aag gaa agt aat 912 Phe Ile Asp Phe
Val Ala Arg Glu Thr Thr Cys Ser Lys Glu Ser Asn 290 295 300 gaa gag
ttg acc gaa agc tgt gag acc aaa aaa ctt ggc caa agc cta 960 Glu Glu
Leu Thr Glu Ser Cys Glu Thr Lys Lys Leu Gly Gln Ser Leu 305 310 315
320 gat tgc aac gct gaa gtt tat gtg gta ccc tgg gag aaa aaa att tac
1008 Asp Cys Asn Ala Glu Val Tyr Val Val Pro Trp Glu Lys Lys Ile
Tyr 325 330 335 cct act gtc aac tgt caa cca ctg gga atg atc tca ctg
atg aaa agg 1056 Pro Thr Val Asn Cys Gln Pro Leu Gly Met Ile Ser
Leu Met Lys Arg 340 345 350 cct cca ggt ttt tca cct ttc cga tca tca
cga ata ggg gaa ata aaa 1104 Pro Pro Gly Phe Ser Pro Phe Arg Ser
Ser Arg Ile Gly Glu Ile Lys 355 360 365 gaa gaa aca act agt cac cta
agg tcc tgc gag tac aag ggt cga ccc 1152 Glu Glu Thr Thr Ser His
Leu Arg Ser Cys Glu Tyr Lys Gly Arg Pro 370 375 380 cca aag gca ggg
gca gag cca gca tct gag agg gag gtc tct 1194 Pro Lys Ala Gly Ala
Glu Pro Ala Ser Glu Arg Glu Val Ser 385 390 395 tgaccaatgg
gcagaatctt cactccaggc acatagcccc aaccacctct 1244 gccagcaacc
ttgagaggaa ggacaagaag aaagatggga tagaatttaa 1294 atagagaaga
atgccatttt atcactctgc ctctgggtga aataaagatc 1344 agtcttgatg ttc
1357 70 398 PRT Homo sapiens 70 Met Lys Leu Ile Thr Ile Leu Phe Leu
Cys Ser Arg Leu Leu Leu Ser 1 5 10 15 Leu Thr Gln Glu Ser Gln Ser
Glu Glu Ile Asp Asp Cys Asn Asp Lys 20 25 30 Asp Leu Phe Lys Ala
Val Asp Ala Ala Leu Lys Lys Tyr Asn Ser Gln 35 40 45 Asn Gln Ser
Asn Asn Gln Phe Val Leu Tyr Arg Lys Thr Trp Gln Asp 50 55 60 Cys
Glu Tyr Lys Asp Ala Ala Lys Ala Ala Thr Gly Glu Cys Thr Ala 65 70
75 80 Thr Val Gly Lys Arg Ser Ser Thr Lys Phe Ser Val Ala Thr Gln
Thr 85 90 95 Cys Gln Ile Thr Pro Ala Glu Gly Pro Val Val Thr Ala
Gln Tyr Asp 100 105 110 Cys Leu Gly Cys Val His Pro Ile Ser Thr Gln
Ser Pro Asp Leu Glu 115 120 125 Pro Ile Leu Arg His Gly Ile Gln Tyr
Phe Asn Asn Asn Thr Gln His 130 135 140 Ser Ser Leu Phe Thr Leu Asn
Glu Val Lys Arg Ala Gln Arg Gln Val 145 150 155 160 Val Ala Gly Leu
Asn Phe Arg Ile Thr Tyr Ser Ile Val Gln Thr Asn 165 170 175 Cys Ser
Lys Glu Asn Phe Leu Phe Leu Thr Pro Asp Cys Lys Ser Leu 180 185 190
Trp Asn Gly Asp Thr Gly Glu Cys Thr Asp Asn Ala Tyr Ile Asp Ile 195
200 205 Gln Leu Arg Ile Ala Ser Phe Ser Gln Asn Cys Asp Ile Tyr Pro
Gly 210 215 220 Lys Asp Phe Val Gln Pro Pro Thr Lys Ile Cys Val Gly
Cys Pro Arg 225 230 235 240 Asp Ile Pro Thr Asn Ser Pro Glu Leu Glu
Glu Thr Leu Thr His Thr 245 250 255 Ile Thr Lys Leu Asn Ala Glu Asn
Asn Ala Thr Phe Tyr Phe Lys Ile 260 265 270 Asp Asn Val Lys Lys Ala
Arg Val Gln Val Val Ala Gly Lys Lys Tyr 275 280 285 Phe Ile Asp Phe
Val Ala Arg Glu Thr Thr Cys Ser Lys Glu Ser Asn 290 295 300 Glu Glu
Leu Thr Glu Ser Cys Glu Thr Lys Lys Leu Gly Gln Ser Leu 305 310 315
320 Asp Cys Asn Ala Glu Val Tyr Val Val Pro Trp Glu Lys Lys Ile Tyr
325 330 335 Pro
Thr Val Asn Cys Gln Pro Leu Gly Met Ile Ser Leu Met Lys Arg 340 345
350 Pro Pro Gly Phe Ser Pro Phe Arg Ser Ser Arg Ile Gly Glu Ile Lys
355 360 365 Glu Glu Thr Thr Ser His Leu Arg Ser Cys Glu Tyr Lys Gly
Arg Pro 370 375 380 Pro Lys Ala Gly Ala Glu Pro Ala Ser Glu Arg Glu
Val Ser 385 390 395 71 1848 DNA Homo sapiens CDS (1)..(1846) 71 atg
aaa cta att acc atc ctt ttc ctc tgc tcc agg cta cta cta agt 48 Met
Lys Leu Ile Thr Ile Leu Phe Leu Cys Ser Arg Leu Leu Leu Ser 1 5 10
15 tta acc cag gaa tca cag tcc gag gaa att gat gac tgc aat gac aag
96 Leu Thr Gln Glu Ser Gln Ser Glu Glu Ile Asp Asp Cys Asn Asp Lys
20 25 30 gat tta ttt aaa gct gtg gat gct gct ctg aag aaa tat aac
agt caa 144 Asp Leu Phe Lys Ala Val Asp Ala Ala Leu Lys Lys Tyr Asn
Ser Gln 35 40 45 aac caa agt aac aac cag ttt gta ttg tac cgc aaa
acc tgg cag gac 192 Asn Gln Ser Asn Asn Gln Phe Val Leu Tyr Arg Lys
Thr Trp Gln Asp 50 55 60 tgt gag tac aag gat gct gca aaa gca gcc
act gga gaa tgc aca gca 240 Cys Glu Tyr Lys Asp Ala Ala Lys Ala Ala
Thr Gly Glu Cys Thr Ala 65 70 75 80 acc gtg ggg aag agg agc agt acg
aaa ttc tcc gtg gct acc cag acc 288 Thr Val Gly Lys Arg Ser Ser Thr
Lys Phe Ser Val Ala Thr Gln Thr 85 90 95 tgc cag att act cca gcc
gag ggc cct gtg gtg aca gcc cag tac gac 336 Cys Gln Ile Thr Pro Ala
Glu Gly Pro Val Val Thr Ala Gln Tyr Asp 100 105 110 tgc ctc ggc tgt
gtg cat cct ata tca acg cag agc cca gac ctg gag 384 Cys Leu Gly Cys
Val His Pro Ile Ser Thr Gln Ser Pro Asp Leu Glu 115 120 125 ccc att
ctg aga cac ggc att cag tac ttt aac aac aac act caa cat 432 Pro Ile
Leu Arg His Gly Ile Gln Tyr Phe Asn Asn Asn Thr Gln His 130 135 140
tcc tcc ctc ttc acg ctt aat gaa gta aaa cgg gcc caa aga cag gtg 480
Ser Ser Leu Phe Thr Leu Asn Glu Val Lys Arg Ala Gln Arg Gln Val 145
150 155 160 gtg gct gga ttg aac ttt cga att acc tac tca att gtg caa
acg aat 528 Val Ala Gly Leu Asn Phe Arg Ile Thr Tyr Ser Ile Val Gln
Thr Asn 165 170 175 tgt tcc aaa gag aat ttt ctg ttc tta act cca gac
tgc aag tcc ctt 576 Cys Ser Lys Glu Asn Phe Leu Phe Leu Thr Pro Asp
Cys Lys Ser Leu 180 185 190 tgg aat ggt gat acc ggt gaa tgt aca gat
aat gca tac atc gat att 624 Trp Asn Gly Asp Thr Gly Glu Cys Thr Asp
Asn Ala Tyr Ile Asp Ile 195 200 205 cag cta cga att gct tcc ttc tca
cag aac tgt gac att tat cca ggg 672 Gln Leu Arg Ile Ala Ser Phe Ser
Gln Asn Cys Asp Ile Tyr Pro Gly 210 215 220 aag gat ttt gta caa cca
cct acc aag att tgc gtg ggc tgc ccc aga 720 Lys Asp Phe Val Gln Pro
Pro Thr Lys Ile Cys Val Gly Cys Pro Arg 225 230 235 240 gat ata ccc
acc aac agc cca gag ctg gag gag aca ctg act cac acc 768 Asp Ile Pro
Thr Asn Ser Pro Glu Leu Glu Glu Thr Leu Thr His Thr 245 250 255 atc
aca aag ctt aat gca gag aat aac gca act ttc tat ttc aag att 816 Ile
Thr Lys Leu Asn Ala Glu Asn Asn Ala Thr Phe Tyr Phe Lys Ile 260 265
270 gac aat gtg aaa aaa gca aga gta cag gtg gtg gct ggc aag aaa tat
864 Asp Asn Val Lys Lys Ala Arg Val Gln Val Val Ala Gly Lys Lys Tyr
275 280 285 ttt att gac ttc gtg gcc agg gaa acc aca tgt tcc aag gaa
agt aat 912 Phe Ile Asp Phe Val Ala Arg Glu Thr Thr Cys Ser Lys Glu
Ser Asn 290 295 300 gaa gag ttg acc gaa agc tgt gag acc aaa aaa ctt
ggc caa agc cta 960 Glu Glu Leu Thr Glu Ser Cys Glu Thr Lys Lys Leu
Gly Gln Ser Leu 305 310 315 320 gat tgc aac gct gaa gtt tat gtg gta
ccc tgg gag aaa aaa att tac 1008 Asp Cys Asn Ala Glu Val Tyr Val
Val Pro Trp Glu Lys Lys Ile Tyr 325 330 335 cct act gtc aac tgt caa
cca ctg gga atg atc tca ctg atg aaa agg 1056 Pro Thr Val Asn Cys
Gln Pro Leu Gly Met Ile Ser Leu Met Lys Arg 340 345 350 cct cca ggt
ttt tca cct ttc cga tca tca cga ata ggg gaa ata aaa 1104 Pro Pro
Gly Phe Ser Pro Phe Arg Ser Ser Arg Ile Gly Glu Ile Lys 355 360 365
gaa gaa aca act gta agt cca ccc cac act tcc atg gca cct gca caa
1152 Glu Glu Thr Thr Val Ser Pro Pro His Thr Ser Met Ala Pro Ala
Gln 370 375 380 gat gaa gag cgg gat tca gga aaa gaa caa ggg cat act
cgt aga cat 1200 Asp Glu Glu Arg Asp Ser Gly Lys Glu Gln Gly His
Thr Arg Arg His 385 390 395 400 gac tgg ggc cat gaa aaa caa aga aaa
cat aat ctt ggc cat ggc cat 1248 Asp Trp Gly His Glu Lys Gln Arg
Lys His Asn Leu Gly His Gly His 405 410 415 aaa cat gaa cgt gac caa
ggg cat ggg cac caa aga gga cat ggc ctt 1296 Lys His Glu Arg Asp
Gln Gly His Gly His Gln Arg Gly His Gly Leu 420 425 430 ggc cat gga
cac gaa caa cag cat ggt ctt ggt cat gga cat aag ttc 1344 Gly His
Gly His Glu Gln Gln His Gly Leu Gly His Gly His Lys Phe 435 440 445
aaa ctt gat gat gat ctt gaa cac caa ggg ggc cat gtc ctt gac cat
1392 Lys Leu Asp Asp Asp Leu Glu His Gln Gly Gly His Val Leu Asp
His 450 455 460 gga cat aag cat aag cat ggt cat ggc cac gga aaa cat
aaa aat aaa 1440 Gly His Lys His Lys His Gly His Gly His Gly Lys
His Lys Asn Lys 465 470 475 480 ggc aaa aag aat gga aag cac aat ggt
tgg aaa aca gag cat ttg gca 1488 Gly Lys Lys Asn Gly Lys His Asn
Gly Trp Lys Thr Glu His Leu Ala 485 490 495 agc tct tct gaa gac agt
act aca cct tct gca cag aca caa gag aag 1536 Ser Ser Ser Glu Asp
Ser Thr Thr Pro Ser Ala Gln Thr Gln Glu Lys 500 505 510 aca gaa ggg
cca aca ccc atc cct tcc cta gcc aag cca ggt gta aca 1584 Thr Glu
Gly Pro Thr Pro Ile Pro Ser Leu Ala Lys Pro Gly Val Thr 515 520 525
gtt acc ttt tct gac ttt cag gac tct gat ctc att gca act atg atg
1632 Val Thr Phe Ser Asp Phe Gln Asp Ser Asp Leu Ile Ala Thr Met
Met 530 535 540 cct cct ata tca cca gct ccc ata cag agt gat gac gat
tgg atc cct 1680 Pro Pro Ile Ser Pro Ala Pro Ile Gln Ser Asp Asp
Asp Trp Ile Pro 545 550 555 560 gat atc cag aca gac cca aat ggc ctt
tca ttt aac cca ata tca gat 1728 Asp Ile Gln Thr Asp Pro Asn Gly
Leu Ser Phe Asn Pro Ile Ser Asp 565 570 575 ttt cca gac acg acc tcc
cca aaa tgt cct gga cgc ccc tgg aag tca 1776 Phe Pro Asp Thr Thr
Ser Pro Lys Cys Pro Gly Arg Pro Trp Lys Ser 580 585 590 gtt agt gaa
att aat cca acc aca caa atg aaa gaa tct tat tat ttc 1824 Val Ser
Glu Ile Asn Pro Thr Thr Gln Met Lys Glu Ser Tyr Tyr Phe 595 600 605
gat ctc act gat ggc ctt tct taa 1848 Asp Leu Thr Asp Gly Leu Ser
610 615 72 615 PRT Homo sapiens 72 Met Lys Leu Ile Thr Ile Leu Phe
Leu Cys Ser Arg Leu Leu Leu Ser 1 5 10 15 Leu Thr Gln Glu Ser Gln
Ser Glu Glu Ile Asp Asp Cys Asn Asp Lys 20 25 30 Asp Leu Phe Lys
Ala Val Asp Ala Ala Leu Lys Lys Tyr Asn Ser Gln 35 40 45 Asn Gln
Ser Asn Asn Gln Phe Val Leu Tyr Arg Lys Thr Trp Gln Asp 50 55 60
Cys Glu Tyr Lys Asp Ala Ala Lys Ala Ala Thr Gly Glu Cys Thr Ala 65
70 75 80 Thr Val Gly Lys Arg Ser Ser Thr Lys Phe Ser Val Ala Thr
Gln Thr 85 90 95 Cys Gln Ile Thr Pro Ala Glu Gly Pro Val Val Thr
Ala Gln Tyr Asp 100 105 110 Cys Leu Gly Cys Val His Pro Ile Ser Thr
Gln Ser Pro Asp Leu Glu 115 120 125 Pro Ile Leu Arg His Gly Ile Gln
Tyr Phe Asn Asn Asn Thr Gln His 130 135 140 Ser Ser Leu Phe Thr Leu
Asn Glu Val Lys Arg Ala Gln Arg Gln Val 145 150 155 160 Val Ala Gly
Leu Asn Phe Arg Ile Thr Tyr Ser Ile Val Gln Thr Asn 165 170 175 Cys
Ser Lys Glu Asn Phe Leu Phe Leu Thr Pro Asp Cys Lys Ser Leu 180 185
190 Trp Asn Gly Asp Thr Gly Glu Cys Thr Asp Asn Ala Tyr Ile Asp Ile
195 200 205 Gln Leu Arg Ile Ala Ser Phe Ser Gln Asn Cys Asp Ile Tyr
Pro Gly 210 215 220 Lys Asp Phe Val Gln Pro Pro Thr Lys Ile Cys Val
Gly Cys Pro Arg 225 230 235 240 Asp Ile Pro Thr Asn Ser Pro Glu Leu
Glu Glu Thr Leu Thr His Thr 245 250 255 Ile Thr Lys Leu Asn Ala Glu
Asn Asn Ala Thr Phe Tyr Phe Lys Ile 260 265 270 Asp Asn Val Lys Lys
Ala Arg Val Gln Val Val Ala Gly Lys Lys Tyr 275 280 285 Phe Ile Asp
Phe Val Ala Arg Glu Thr Thr Cys Ser Lys Glu Ser Asn 290 295 300 Glu
Glu Leu Thr Glu Ser Cys Glu Thr Lys Lys Leu Gly Gln Ser Leu 305 310
315 320 Asp Cys Asn Ala Glu Val Tyr Val Val Pro Trp Glu Lys Lys Ile
Tyr 325 330 335 Pro Thr Val Asn Cys Gln Pro Leu Gly Met Ile Ser Leu
Met Lys Arg 340 345 350 Pro Pro Gly Phe Ser Pro Phe Arg Ser Ser Arg
Ile Gly Glu Ile Lys 355 360 365 Glu Glu Thr Thr Val Ser Pro Pro His
Thr Ser Met Ala Pro Ala Gln 370 375 380 Asp Glu Glu Arg Asp Ser Gly
Lys Glu Gln Gly His Thr Arg Arg His 385 390 395 400 Asp Trp Gly His
Glu Lys Gln Arg Lys His Asn Leu Gly His Gly His 405 410 415 Lys His
Glu Arg Asp Gln Gly His Gly His Gln Arg Gly His Gly Leu 420 425 430
Gly His Gly His Glu Gln Gln His Gly Leu Gly His Gly His Lys Phe 435
440 445 Lys Leu Asp Asp Asp Leu Glu His Gln Gly Gly His Val Leu Asp
His 450 455 460 Gly His Lys His Lys His Gly His Gly His Gly Lys His
Lys Asn Lys 465 470 475 480 Gly Lys Lys Asn Gly Lys His Asn Gly Trp
Lys Thr Glu His Leu Ala 485 490 495 Ser Ser Ser Glu Asp Ser Thr Thr
Pro Ser Ala Gln Thr Gln Glu Lys 500 505 510 Thr Glu Gly Pro Thr Pro
Ile Pro Ser Leu Ala Lys Pro Gly Val Thr 515 520 525 Val Thr Phe Ser
Asp Phe Gln Asp Ser Asp Leu Ile Ala Thr Met Met 530 535 540 Pro Pro
Ile Ser Pro Ala Pro Ile Gln Ser Asp Asp Asp Trp Ile Pro 545 550 555
560 Asp Ile Gln Thr Asp Pro Asn Gly Leu Ser Phe Asn Pro Ile Ser Asp
565 570 575 Phe Pro Asp Thr Thr Ser Pro Lys Cys Pro Gly Arg Pro Trp
Lys Ser 580 585 590 Val Ser Glu Ile Asn Pro Thr Thr Gln Met Lys Glu
Ser Tyr Tyr Phe 595 600 605 Asp Leu Thr Asp Gly Leu Ser 610 615 73
1981 DNA Homo sapiens CDS (50)..(1981) 73 aattccggtt gaaaccatcc
ctcagctcct agagggagat tgttagatc atg aaa 55 Met Lys 1 cta att acc
atc ctt ttc ctc tgc tcc agg cta cta cta agt tta acc 103 Leu Ile Thr
Ile Leu Phe Leu Cys Ser Arg Leu Leu Leu Ser Leu Thr 5 10 15 cag gaa
tca cag tcc gag gaa att gac tgc aat gac aag gat tta ttt 151 Gln Glu
Ser Gln Ser Glu Glu Ile Asp Cys Asn Asp Lys Asp Leu Phe 20 25 30
aaa gct gtg gat gct gct ctg aag aaa tat aac agt caa aac caa agt 199
Lys Ala Val Asp Ala Ala Leu Lys Lys Tyr Asn Ser Gln Asn Gln Ser 35
40 45 50 aac aac cag ttt gta ttg tac cgc ata act gaa gcc act aag
acg gtt 247 Asn Asn Gln Phe Val Leu Tyr Arg Ile Thr Glu Ala Thr Lys
Thr Val 55 60 65 ggc tct gac acg ttt tat tcc ttc aag tac gaa atc
aag gag ggg gat 295 Gly Ser Asp Thr Phe Tyr Ser Phe Lys Tyr Glu Ile
Lys Glu Gly Asp 70 75 80 tgt cct gtt caa agt ggc aaa acc tgg cag
gac tgt gag tac aag gat 343 Cys Pro Val Gln Ser Gly Lys Thr Trp Gln
Asp Cys Glu Tyr Lys Asp 85 90 95 gct gca aaa gca gcc act gga gaa
tgc acg gca acc gtg ggg aag agg 391 Ala Ala Lys Ala Ala Thr Gly Glu
Cys Thr Ala Thr Val Gly Lys Arg 100 105 110 agc agt acg aaa ttc tcc
gtg gct acc cag acc tgc cag att act cca 439 Ser Ser Thr Lys Phe Ser
Val Ala Thr Gln Thr Cys Gln Ile Thr Pro 115 120 125 130 gcc gag ggc
cct gtg gtg aca gcc cag tac gac tgc ctc ggc tgt gtg 487 Ala Glu Gly
Pro Val Val Thr Ala Gln Tyr Asp Cys Leu Gly Cys Val 135 140 145 cat
cct ata tca acg cag agc cca gac ctg gag ccc att ctg aga cac 535 His
Pro Ile Ser Thr Gln Ser Pro Asp Leu Glu Pro Ile Leu Arg His 150 155
160 ggc att cag tac ttt aac aac aac act caa cat tcc tcc ctc ttc atg
583 Gly Ile Gln Tyr Phe Asn Asn Asn Thr Gln His Ser Ser Leu Phe Met
165 170 175 ctt aat gaa gta aaa cgg gcc caa aga cag gtg gtg gct gga
ttg aac 631 Leu Asn Glu Val Lys Arg Ala Gln Arg Gln Val Val Ala Gly
Leu Asn 180 185 190 ttt cga att acc tac tca att gtg caa acg aat tgt
tcc aaa gag aat 679 Phe Arg Ile Thr Tyr Ser Ile Val Gln Thr Asn Cys
Ser Lys Glu Asn 195 200 205 210 ttt ctg ttc tta act cca gac tgc aag
tcc ctt tgg aat ggt gat acc 727 Phe Leu Phe Leu Thr Pro Asp Cys Lys
Ser Leu Trp Asn Gly Asp Thr 215 220 225 ggt gaa tgt aca gat aat gca
tac atc gat att cag cta cga att gct 775 Gly Glu Cys Thr Asp Asn Ala
Tyr Ile Asp Ile Gln Leu Arg Ile Ala 230 235 240 tcc ttc tca cag aac
tgt gac att tat cca ggg aag gat ttt gta caa 823 Ser Phe Ser Gln Asn
Cys Asp Ile Tyr Pro Gly Lys Asp Phe Val Gln 245 250 255 cca cct acc
aag att tgc gtg ggc tgc ccc aga gat ata ccc acc aac 871 Pro Pro Thr
Lys Ile Cys Val Gly Cys Pro Arg Asp Ile Pro Thr Asn 260 265 270 agc
cca gag ctg gag gag aca ctg act cac acc atc aca aag ctt aat 919 Ser
Pro Glu Leu Glu Glu Thr Leu Thr His Thr Ile Thr Lys Leu Asn 275 280
285 290 gca gag aat aac gca act ttc tat ttc aag att gac aat gtg aaa
aaa 967 Ala Glu Asn Asn Ala Thr Phe Tyr Phe Lys Ile Asp Asn Val Lys
Lys 295 300 305 gca aga gta cag gtg gtg gct ggc aag aaa tat ttt att
gac ttc gtg 1015 Ala Arg Val Gln Val Val Ala Gly Lys Lys Tyr Phe
Ile Asp Phe Val 310 315 320 gcc agg gaa acc aca tgt tcc aag gaa agt
aat gaa gag ttg acc gaa 1063 Ala Arg Glu Thr Thr Cys Ser Lys Glu
Ser Asn Glu Glu Leu Thr Glu 325 330 335 agc tgt gag acc aaa aaa ctt
ggc caa agc cta gat tgc aac gct gaa 1111 Ser Cys Glu Thr Lys Lys
Leu Gly Gln Ser Leu Asp Cys Asn Ala Glu 340 345 350 gtt tat gtg gta
ccc tgg gag aaa aaa att tac cct act gtc aac tgt 1159 Val Tyr Val
Val Pro Trp Glu Lys Lys Ile Tyr Pro Thr Val Asn Cys 355 360 365 370
caa cca ctg gga atg atc tca ctg atg aaa agg cct cca ggt ttt tca
1207 Gln Pro Leu Gly Met Ile Ser Leu Met Lys Arg Pro Pro Gly Phe
Ser 375 380 385 cct ttc cga tca tca cga ata ggg gaa ata aaa gaa gaa
aca act gta 1255 Pro Phe Arg Ser Ser Arg Ile Gly Glu Ile Lys Glu
Glu Thr Thr Val 390 395 400 agt cca ccc cac act tcc atg gca cct gca
caa gat gaa gag cgg gat 1303 Ser Pro Pro His Thr Ser Met Ala Pro
Ala Gln Asp Glu Glu Arg Asp 405 410 415 tca gga aaa gaa caa ggg cat
act cgt aga cat gac tgg ggc cat gaa 1351 Ser Gly Lys Glu Gln Gly
His Thr Arg Arg His Asp Trp Gly His Glu 420 425 430 aaa caa aga aaa
cat aat ctt ggc cat ggc cat aaa cat gaa cgt gac 1399 Lys Gln Arg
Lys His Asn Leu Gly His Gly His Lys His Glu Arg Asp 435 440 445 450
caa ggg cat ggg cac caa aga gga cat ggc ctt ggc cat gga cac gaa
1447 Gln Gly His Gly His Gln Arg Gly His Gly Leu Gly His Gly
His Glu 455 460 465 caa cag cat ggt ctt ggt cat gga cat aag ttc aaa
ctt gat gat gat 1495 Gln Gln His Gly Leu Gly His Gly His Lys Phe
Lys Leu Asp Asp Asp 470 475 480 ctt gaa cac caa ggg ggc cat gtc ctt
gac cat gga cat aag cat aag 1543 Leu Glu His Gln Gly Gly His Val
Leu Asp His Gly His Lys His Lys 485 490 495 cat ggt cat ggc cac gga
aaa cat aaa aat aaa ggc aaa aag aat gga 1591 His Gly His Gly His
Gly Lys His Lys Asn Lys Gly Lys Lys Asn Gly 500 505 510 aag cac aat
ggt tgg aaa aca gag cat ttg gca agc tct tct gaa gac 1639 Lys His
Asn Gly Trp Lys Thr Glu His Leu Ala Ser Ser Ser Glu Asp 515 520 525
530 agt act aca cct tct gca cag aca caa gag aag aca gaa ggg cca aca
1687 Ser Thr Thr Pro Ser Ala Gln Thr Gln Glu Lys Thr Glu Gly Pro
Thr 535 540 545 ccc atc cct tcc cta gcc aag cca ggt gta aca gtt acc
ttt tct gac 1735 Pro Ile Pro Ser Leu Ala Lys Pro Gly Val Thr Val
Thr Phe Ser Asp 550 555 560 ttt cag gac tct gat ctc att gca act atg
atg cct cct ata tca cca 1783 Phe Gln Asp Ser Asp Leu Ile Ala Thr
Met Met Pro Pro Ile Ser Pro 565 570 575 gct ccc ata cag agt gat gac
gat tgg atc cct gat atc cag ata gac 1831 Ala Pro Ile Gln Ser Asp
Asp Asp Trp Ile Pro Asp Ile Gln Ile Asp 580 585 590 cca aat ggc ctt
tca ttt aac cca ata tca gat ttt cca gac acg acc 1879 Pro Asn Gly
Leu Ser Phe Asn Pro Ile Ser Asp Phe Pro Asp Thr Thr 595 600 605 610
tcc cca aaa tgt cct gga cgc ccc tgg aag tca gtt agt gaa att aat
1927 Ser Pro Lys Cys Pro Gly Arg Pro Trp Lys Ser Val Ser Glu Ile
Asn 615 620 625 cca acc aca caa atg aaa gaa tct tat tat ttc gat ctc
act gat ggc 1975 Pro Thr Thr Gln Met Lys Glu Ser Tyr Tyr Phe Asp
Leu Thr Asp Gly 630 635 640 ctt tct 1981 Leu Ser 74 644 PRT Homo
sapiens 74 Met Lys Leu Ile Thr Ile Leu Phe Leu Cys Ser Arg Leu Leu
Leu Ser 1 5 10 15 Leu Thr Gln Glu Ser Gln Ser Glu Glu Ile Asp Cys
Asn Asp Lys Asp 20 25 30 Leu Phe Lys Ala Val Asp Ala Ala Leu Lys
Lys Tyr Asn Ser Gln Asn 35 40 45 Gln Ser Asn Asn Gln Phe Val Leu
Tyr Arg Ile Thr Glu Ala Thr Lys 50 55 60 Thr Val Gly Ser Asp Thr
Phe Tyr Ser Phe Lys Tyr Glu Ile Lys Glu 65 70 75 80 Gly Asp Cys Pro
Val Gln Ser Gly Lys Thr Trp Gln Asp Cys Glu Tyr 85 90 95 Lys Asp
Ala Ala Lys Ala Ala Thr Gly Glu Cys Thr Ala Thr Val Gly 100 105 110
Lys Arg Ser Ser Thr Lys Phe Ser Val Ala Thr Gln Thr Cys Gln Ile 115
120 125 Thr Pro Ala Glu Gly Pro Val Val Thr Ala Gln Tyr Asp Cys Leu
Gly 130 135 140 Cys Val His Pro Ile Ser Thr Gln Ser Pro Asp Leu Glu
Pro Ile Leu 145 150 155 160 Arg His Gly Ile Gln Tyr Phe Asn Asn Asn
Thr Gln His Ser Ser Leu 165 170 175 Phe Met Leu Asn Glu Val Lys Arg
Ala Gln Arg Gln Val Val Ala Gly 180 185 190 Leu Asn Phe Arg Ile Thr
Tyr Ser Ile Val Gln Thr Asn Cys Ser Lys 195 200 205 Glu Asn Phe Leu
Phe Leu Thr Pro Asp Cys Lys Ser Leu Trp Asn Gly 210 215 220 Asp Thr
Gly Glu Cys Thr Asp Asn Ala Tyr Ile Asp Ile Gln Leu Arg 225 230 235
240 Ile Ala Ser Phe Ser Gln Asn Cys Asp Ile Tyr Pro Gly Lys Asp Phe
245 250 255 Val Gln Pro Pro Thr Lys Ile Cys Val Gly Cys Pro Arg Asp
Ile Pro 260 265 270 Thr Asn Ser Pro Glu Leu Glu Glu Thr Leu Thr His
Thr Ile Thr Lys 275 280 285 Leu Asn Ala Glu Asn Asn Ala Thr Phe Tyr
Phe Lys Ile Asp Asn Val 290 295 300 Lys Lys Ala Arg Val Gln Val Val
Ala Gly Lys Lys Tyr Phe Ile Asp 305 310 315 320 Phe Val Ala Arg Glu
Thr Thr Cys Ser Lys Glu Ser Asn Glu Glu Leu 325 330 335 Thr Glu Ser
Cys Glu Thr Lys Lys Leu Gly Gln Ser Leu Asp Cys Asn 340 345 350 Ala
Glu Val Tyr Val Val Pro Trp Glu Lys Lys Ile Tyr Pro Thr Val 355 360
365 Asn Cys Gln Pro Leu Gly Met Ile Ser Leu Met Lys Arg Pro Pro Gly
370 375 380 Phe Ser Pro Phe Arg Ser Ser Arg Ile Gly Glu Ile Lys Glu
Glu Thr 385 390 395 400 Thr Val Ser Pro Pro His Thr Ser Met Ala Pro
Ala Gln Asp Glu Glu 405 410 415 Arg Asp Ser Gly Lys Glu Gln Gly His
Thr Arg Arg His Asp Trp Gly 420 425 430 His Glu Lys Gln Arg Lys His
Asn Leu Gly His Gly His Lys His Glu 435 440 445 Arg Asp Gln Gly His
Gly His Gln Arg Gly His Gly Leu Gly His Gly 450 455 460 His Glu Gln
Gln His Gly Leu Gly His Gly His Lys Phe Lys Leu Asp 465 470 475 480
Asp Asp Leu Glu His Gln Gly Gly His Val Leu Asp His Gly His Lys 485
490 495 His Lys His Gly His Gly His Gly Lys His Lys Asn Lys Gly Lys
Lys 500 505 510 Asn Gly Lys His Asn Gly Trp Lys Thr Glu His Leu Ala
Ser Ser Ser 515 520 525 Glu Asp Ser Thr Thr Pro Ser Ala Gln Thr Gln
Glu Lys Thr Glu Gly 530 535 540 Pro Thr Pro Ile Pro Ser Leu Ala Lys
Pro Gly Val Thr Val Thr Phe 545 550 555 560 Ser Asp Phe Gln Asp Ser
Asp Leu Ile Ala Thr Met Met Pro Pro Ile 565 570 575 Ser Pro Ala Pro
Ile Gln Ser Asp Asp Asp Trp Ile Pro Asp Ile Gln 580 585 590 Ile Asp
Pro Asn Gly Leu Ser Phe Asn Pro Ile Ser Asp Phe Pro Asp 595 600 605
Thr Thr Ser Pro Lys Cys Pro Gly Arg Pro Trp Lys Ser Val Ser Glu 610
615 620 Ile Asn Pro Thr Thr Gln Met Lys Glu Ser Tyr Tyr Phe Asp Leu
Thr 625 630 635 640 Asp Gly Leu Ser 75 1297 DNA Homo sapiens CDS
(50)..(1295) 75 aattccggtt gaaaccatcc ctcagctcct agagggagat
tgttagatc atg aaa 55 Met Lys 1 cta att acc atc ctt ttc ctc tgc tcc
agg cta cta cta agt tta acc 103 Leu Ile Thr Ile Leu Phe Leu Cys Ser
Arg Leu Leu Leu Ser Leu Thr 5 10 15 cag gaa tca cag tcc gag gaa att
gac tgc aat gac aag gat tta ttt 151 Gln Glu Ser Gln Ser Glu Glu Ile
Asp Cys Asn Asp Lys Asp Leu Phe 20 25 30 aaa gct gtg gat gct gct
ctg aag aaa tat aac agt caa aac caa agt 199 Lys Ala Val Asp Ala Ala
Leu Lys Lys Tyr Asn Ser Gln Asn Gln Ser 35 40 45 50 aac aac cag ttt
gta ttg tac cgc ata act gaa gcc act aag acg gtt 247 Asn Asn Gln Phe
Val Leu Tyr Arg Ile Thr Glu Ala Thr Lys Thr Val 55 60 65 ggc tct
gac acg ttt tat tcc ttc aag tac gaa atc aag gag ggg gat 295 Gly Ser
Asp Thr Phe Tyr Ser Phe Lys Tyr Glu Ile Lys Glu Gly Asp 70 75 80
tgt cct gtt caa agt ggc aaa acc tgg cag gac tgt gag tac aag gat 343
Cys Pro Val Gln Ser Gly Lys Thr Trp Gln Asp Cys Glu Tyr Lys Asp 85
90 95 gct gca aaa gca gcc act gga gaa tgc aca gca acc gtg ggg aag
agg 391 Ala Ala Lys Ala Ala Thr Gly Glu Cys Thr Ala Thr Val Gly Lys
Arg 100 105 110 agc agt acg aaa ttc tcc gtg gct acc cag acc tgc cag
att act cca 439 Ser Ser Thr Lys Phe Ser Val Ala Thr Gln Thr Cys Gln
Ile Thr Pro 115 120 125 130 gcc gag ggc cct gtg gtg aca gcc cag tac
gac tgc ctc ggc tgt gtg 487 Ala Glu Gly Pro Val Val Thr Ala Gln Tyr
Asp Cys Leu Gly Cys Val 135 140 145 cat cct ata tca acg cag agc cca
ggt ttt tca cct ttc cga tca tca 535 His Pro Ile Ser Thr Gln Ser Pro
Gly Phe Ser Pro Phe Arg Ser Ser 150 155 160 cga ata ggg gaa ata aaa
gaa gaa aca act gta agt cca ccc cac act 583 Arg Ile Gly Glu Ile Lys
Glu Glu Thr Thr Val Ser Pro Pro His Thr 165 170 175 tcc atg gca cct
gca caa gat gaa gag cgg gat tca gga aaa gaa caa 631 Ser Met Ala Pro
Ala Gln Asp Glu Glu Arg Asp Ser Gly Lys Glu Gln 180 185 190 ggg cat
act cgt aga cat gac tgg ggc cat gaa aaa caa aga aaa cat 679 Gly His
Thr Arg Arg His Asp Trp Gly His Glu Lys Gln Arg Lys His 195 200 205
210 aat ctt ggc cat ggc cat aaa cat gaa cgt gac caa ggg cat ggg cac
727 Asn Leu Gly His Gly His Lys His Glu Arg Asp Gln Gly His Gly His
215 220 225 caa aga gga cat ggc ctt ggc cat gga cac gaa caa cag cat
ggt ctt 775 Gln Arg Gly His Gly Leu Gly His Gly His Glu Gln Gln His
Gly Leu 230 235 240 ggt cat gga cat aag ttc aaa ctt gat gat gat ctt
gaa cac caa ggg 823 Gly His Gly His Lys Phe Lys Leu Asp Asp Asp Leu
Glu His Gln Gly 245 250 255 ggc cat gtc ctt gac cat gga cat aag cat
aag cat ggt cat ggc cac 871 Gly His Val Leu Asp His Gly His Lys His
Lys His Gly His Gly His 260 265 270 gga aaa cat aaa aat aaa ggc aaa
aag aat gga aag cac aat ggt tgg 919 Gly Lys His Lys Asn Lys Gly Lys
Lys Asn Gly Lys His Asn Gly Trp 275 280 285 290 aaa aca gag cat ttg
gca agc tct tct gaa gac agt act aca cct tct 967 Lys Thr Glu His Leu
Ala Ser Ser Ser Glu Asp Ser Thr Thr Pro Ser 295 300 305 gca cag aca
caa gag aag aca gaa ggg cca aca ccc atc cct tcc cta 1015 Ala Gln
Thr Gln Glu Lys Thr Glu Gly Pro Thr Pro Ile Pro Ser Leu 310 315 320
gcc aag cca ggt gta aca gtt acc ttt tct gac ttt cag gac tct gat
1063 Ala Lys Pro Gly Val Thr Val Thr Phe Ser Asp Phe Gln Asp Ser
Asp 325 330 335 ctc att gca act atg atg cct cct ata tca cca gct ccc
ata cag agt 1111 Leu Ile Ala Thr Met Met Pro Pro Ile Ser Pro Ala
Pro Ile Gln Ser 340 345 350 gat gac gat tgg atc cct gat atc cag ata
gac cca aat ggc ctt tca 1159 Asp Asp Asp Trp Ile Pro Asp Ile Gln
Ile Asp Pro Asn Gly Leu Ser 355 360 365 370 ttt aac cca ata tca gat
ttt cca gac acg acc tcc cca aaa tgt cct 1207 Phe Asn Pro Ile Ser
Asp Phe Pro Asp Thr Thr Ser Pro Lys Cys Pro 375 380 385 gga cgc ccc
tgg aag tca gtt agt gaa att aat cca acc aca caa atg 1255 Gly Arg
Pro Trp Lys Ser Val Ser Glu Ile Asn Pro Thr Thr Gln Met 390 395 400
aaa gaa tct tat tat ttc gat ctc act gat ggc ctt tct taa 1297 Lys
Glu Ser Tyr Tyr Phe Asp Leu Thr Asp Gly Leu Ser 405 410 415 76 415
PRT Homo sapiens 76 Met Lys Leu Ile Thr Ile Leu Phe Leu Cys Ser Arg
Leu Leu Leu Ser 1 5 10 15 Leu Thr Gln Glu Ser Gln Ser Glu Glu Ile
Asp Cys Asn Asp Lys Asp 20 25 30 Leu Phe Lys Ala Val Asp Ala Ala
Leu Lys Lys Tyr Asn Ser Gln Asn 35 40 45 Gln Ser Asn Asn Gln Phe
Val Leu Tyr Arg Ile Thr Glu Ala Thr Lys 50 55 60 Thr Val Gly Ser
Asp Thr Phe Tyr Ser Phe Lys Tyr Glu Ile Lys Glu 65 70 75 80 Gly Asp
Cys Pro Val Gln Ser Gly Lys Thr Trp Gln Asp Cys Glu Tyr 85 90 95
Lys Asp Ala Ala Lys Ala Ala Thr Gly Glu Cys Thr Ala Thr Val Gly 100
105 110 Lys Arg Ser Ser Thr Lys Phe Ser Val Ala Thr Gln Thr Cys Gln
Ile 115 120 125 Thr Pro Ala Glu Gly Pro Val Val Thr Ala Gln Tyr Asp
Cys Leu Gly 130 135 140 Cys Val His Pro Ile Ser Thr Gln Ser Pro Gly
Phe Ser Pro Phe Arg 145 150 155 160 Ser Ser Arg Ile Gly Glu Ile Lys
Glu Glu Thr Thr Val Ser Pro Pro 165 170 175 His Thr Ser Met Ala Pro
Ala Gln Asp Glu Glu Arg Asp Ser Gly Lys 180 185 190 Glu Gln Gly His
Thr Arg Arg His Asp Trp Gly His Glu Lys Gln Arg 195 200 205 Lys His
Asn Leu Gly His Gly His Lys His Glu Arg Asp Gln Gly His 210 215 220
Gly His Gln Arg Gly His Gly Leu Gly His Gly His Glu Gln Gln His 225
230 235 240 Gly Leu Gly His Gly His Lys Phe Lys Leu Asp Asp Asp Leu
Glu His 245 250 255 Gln Gly Gly His Val Leu Asp His Gly His Lys His
Lys His Gly His 260 265 270 Gly His Gly Lys His Lys Asn Lys Gly Lys
Lys Asn Gly Lys His Asn 275 280 285 Gly Trp Lys Thr Glu His Leu Ala
Ser Ser Ser Glu Asp Ser Thr Thr 290 295 300 Pro Ser Ala Gln Thr Gln
Glu Lys Thr Glu Gly Pro Thr Pro Ile Pro 305 310 315 320 Ser Leu Ala
Lys Pro Gly Val Thr Val Thr Phe Ser Asp Phe Gln Asp 325 330 335 Ser
Asp Leu Ile Ala Thr Met Met Pro Pro Ile Ser Pro Ala Pro Ile 340 345
350 Gln Ser Asp Asp Asp Trp Ile Pro Asp Ile Gln Ile Asp Pro Asn Gly
355 360 365 Leu Ser Phe Asn Pro Ile Ser Asp Phe Pro Asp Thr Thr Ser
Pro Lys 370 375 380 Cys Pro Gly Arg Pro Trp Lys Ser Val Ser Glu Ile
Asn Pro Thr Thr 385 390 395 400 Gln Met Lys Glu Ser Tyr Tyr Phe Asp
Leu Thr Asp Gly Leu Ser 405 410 415 77 1892 DNA Homo sapiens CDS
(50)..(458) 77 aattccggtt gaaaccatcc ctcagctcct agagggagat
tgttagatc atg aaa 55 Met Lys 1 cta att acc atc ctt ttc ctc tgc tcc
agg cta cta cta agt tta acc 103 Leu Ile Thr Ile Leu Phe Leu Cys Ser
Arg Leu Leu Leu Ser Leu Thr 5 10 15 cag gaa tca cag tcc gag gaa att
gac tgc aat gac aag gat tta ttt 151 Gln Glu Ser Gln Ser Glu Glu Ile
Asp Cys Asn Asp Lys Asp Leu Phe 20 25 30 aaa gct gtg gat gct gct
ctg aag aaa tat aac agt caa aac caa agt 199 Lys Ala Val Asp Ala Ala
Leu Lys Lys Tyr Asn Ser Gln Asn Gln Ser 35 40 45 50 aac aac cag ttt
gta ttg tac cgc ata act gaa gcc act aag acg gtt 247 Asn Asn Gln Phe
Val Leu Tyr Arg Ile Thr Glu Ala Thr Lys Thr Val 55 60 65 ggc tct
gac acg ttt tat tcc ttc aag tac gaa atc aag gag ggg gat 295 Gly Ser
Asp Thr Phe Tyr Ser Phe Lys Tyr Glu Ile Lys Glu Gly Asp 70 75 80
tgt cct gtt caa agt ggc aaa acc tgg cag gac tgt gag tac aag gat 343
Cys Pro Val Gln Ser Gly Lys Thr Trp Gln Asp Cys Glu Tyr Lys Asp 85
90 95 gct gca aaa gca gcc act gga gaa tgc aca gca acc gtg gga aga
gga 391 Ala Ala Lys Ala Ala Thr Gly Glu Cys Thr Ala Thr Val Gly Arg
Gly 100 105 110 gca gta cga aat tct ccg tgg cta ccc aga cct gga gcc
cat tct gag 439 Ala Val Arg Asn Ser Pro Trp Leu Pro Arg Pro Gly Ala
His Ser Glu 115 120 125 130 aca cgg cat tca gta ctt taacaacaac
actcaacatt cctccctctt 487 Thr Arg His Ser Val Leu 135 cacgcttaat
gaagtaaaac gggcccaaag acaggtggtg gctggattga 537 actttcgaat
tacctactca attgtgcaaa cgaattgttc caaagagaat 587 tttctgttct
taactccaga ctgcaagtcc ctttggaatg gtgataccgg 637 tgaatgtaca
gataatgcat acatcgatat tcagctacga attgcttcct 687 tctcacagaa
ctgtgacatt tatccaggga aggattttgt acaaccacct 737 accaagattt
gcgtgggctg ccccagagat atacccacca acagcccaga 787 gctggaggag
acactgactc acaccatcac aaagcttaat gcagagaata 837 acgcaacttt
ctatttcaag attgacaatg tgaaaaaagc aagagtacag 887 gtggtggctg
gcaagaaata ttttattgac ttcgtggcca gggaaaccac 937 atgttccaag
gaaagtaatg aagagttgac cgaaagctgt gagaccaaaa 987 aacttggcca
aagcctagat tgcaacgctg aagtttatgt ggtaccctgg 1037 gagaaaaaaa
tttaccctac tgtcaactgt caaccactgg gaatgatctc 1087 actgatgaaa
aggcctccag gtttttcacc tttccgatca tcacgaatag 1137
gggaaataaa agaagaaaca actgtaagtc caccccacac ttccatggca 1187
cctgcacaag atgaagagcg ggattcagga aaagaacaag ggcatactcg 1237
tagacatgac tggggccatg aaaaacaaag aaaacataat cttggccatg 1287
gccataaaca tgaacgtgac caagggcatg ggcaccaaag aggacatggc 1337
cttggccatg gacacgaaca acagcatggt cttggtcatg gacataagtt 1387
caaacttgat gatgatcttg aacaccaagg gggccatgtc cttgaccatg 1437
gacataagca taagcatggt catggccacg gaaaacataa aaataaaggc 1487
aaaaagaatg gaaagcacaa tggttggaaa acagagcatt tggcaagctc 1537
ttctgaagac agtactacac cttctgcaca gacacaagag aagacagaag 1587
ggccaacacc catcccttcc ctagccaagc caggtgtaac agttaccttt 1637
tctgactttc aggactctga tctcattgca actatgatgc ctcctatatc 1687
accagctccc atacagagtg atgacgattg gatccctgat atccagatag 1737
acccaaatgg cctttcattt aacccaatat cagattttcc agacacgacc 1787
tccccaaaat gtcctggacg cccctggaag tcagttagtg aaattaatcc 1837
aaccacacaa atgaaagaat cttattattt cgatctcact gatggccttt 1887 cttaa
1892 78 136 PRT Homo sapiens 78 Met Lys Leu Ile Thr Ile Leu Phe Leu
Cys Ser Arg Leu Leu Leu Ser 1 5 10 15 Leu Thr Gln Glu Ser Gln Ser
Glu Glu Ile Asp Cys Asn Asp Lys Asp 20 25 30 Leu Phe Lys Ala Val
Asp Ala Ala Leu Lys Lys Tyr Asn Ser Gln Asn 35 40 45 Gln Ser Asn
Asn Gln Phe Val Leu Tyr Arg Ile Thr Glu Ala Thr Lys 50 55 60 Thr
Val Gly Ser Asp Thr Phe Tyr Ser Phe Lys Tyr Glu Ile Lys Glu 65 70
75 80 Gly Asp Cys Pro Val Gln Ser Gly Lys Thr Trp Gln Asp Cys Glu
Tyr 85 90 95 Lys Asp Ala Ala Lys Ala Ala Thr Gly Glu Cys Thr Ala
Thr Val Gly 100 105 110 Arg Gly Ala Val Arg Asn Ser Pro Trp Leu Pro
Arg Pro Gly Ala His 115 120 125 Ser Glu Thr Arg His Ser Val Leu 130
135 79 670 DNA Homo sapiens CDS (1)..(508) 79 atg aaa cta att acc
atc ctt ttc ctc tgc tcc agg cta cta cta agt 48 Met Lys Leu Ile Thr
Ile Leu Phe Leu Cys Ser Arg Leu Leu Leu Ser 1 5 10 15 tta acc cag
gaa tca cag tcc gag gaa att gat gac tgc aat gac aag 96 Leu Thr Gln
Glu Ser Gln Ser Glu Glu Ile Asp Asp Cys Asn Asp Lys 20 25 30 gat
tta ttt aaa gct gtg gat gct gct ctg aag aaa tat aac agt caa 144 Asp
Leu Phe Lys Ala Val Asp Ala Ala Leu Lys Lys Tyr Asn Ser Gln 35 40
45 aac caa agt aac aac cag ttt gta ttg tac cgc aaa acc tgg cag gac
192 Asn Gln Ser Asn Asn Gln Phe Val Leu Tyr Arg Lys Thr Trp Gln Asp
50 55 60 tgt gag tac aag gat gct gca aaa gca gcc act gga gaa tgc
aca gca 240 Cys Glu Tyr Lys Asp Ala Ala Lys Ala Ala Thr Gly Glu Cys
Thr Ala 65 70 75 80 acc gtg ggg aag agg agc agt acg aaa ttc tcc gtg
gct acc cag acc 288 Thr Val Gly Lys Arg Ser Ser Thr Lys Phe Ser Val
Ala Thr Gln Thr 85 90 95 tgc cag att act cca gcc gag ggc cct gtg
gtg aca gcc cag tac gac 336 Cys Gln Ile Thr Pro Ala Glu Gly Pro Val
Val Thr Ala Gln Tyr Asp 100 105 110 tgc ctc ggc tgt gtg cat cct ata
tca acg cag agc cca ggt ttt tca 384 Cys Leu Gly Cys Val His Pro Ile
Ser Thr Gln Ser Pro Gly Phe Ser 115 120 125 cct ttc cga tca tca cga
ata ggg gaa ata aaa gaa gaa aca act agt 432 Pro Phe Arg Ser Ser Arg
Ile Gly Glu Ile Lys Glu Glu Thr Thr Ser 130 135 140 cac cta agg tcc
tgc gag tac aag ggt cga ccc cca aag gca ggg gca 480 His Leu Arg Ser
Cys Glu Tyr Lys Gly Arg Pro Pro Lys Ala Gly Ala 145 150 155 160 gag
cca gca tct gag agg gag gtc tct tgaccaatgg gcagaatctt 527 Glu Pro
Ala Ser Glu Arg Glu Val Ser 165 cactccaggc acatagcccc aaccacctct
gccagcaacc ttgagaggaa 577 ggacaagaag aaagatggga tagaatttaa
atagagaaga atgccatttt 627 atcactctgc ctctgggtga aataaagatc
agtcttgatg ttc 670 80 169 PRT Homo sapiens 80 Met Lys Leu Ile Thr
Ile Leu Phe Leu Cys Ser Arg Leu Leu Leu Ser 1 5 10 15 Leu Thr Gln
Glu Ser Gln Ser Glu Glu Ile Asp Asp Cys Asn Asp Lys 20 25 30 Asp
Leu Phe Lys Ala Val Asp Ala Ala Leu Lys Lys Tyr Asn Ser Gln 35 40
45 Asn Gln Ser Asn Asn Gln Phe Val Leu Tyr Arg Lys Thr Trp Gln Asp
50 55 60 Cys Glu Tyr Lys Asp Ala Ala Lys Ala Ala Thr Gly Glu Cys
Thr Ala 65 70 75 80 Thr Val Gly Lys Arg Ser Ser Thr Lys Phe Ser Val
Ala Thr Gln Thr 85 90 95 Cys Gln Ile Thr Pro Ala Glu Gly Pro Val
Val Thr Ala Gln Tyr Asp 100 105 110 Cys Leu Gly Cys Val His Pro Ile
Ser Thr Gln Ser Pro Gly Phe Ser 115 120 125 Pro Phe Arg Ser Ser Arg
Ile Gly Glu Ile Lys Glu Glu Thr Thr Ser 130 135 140 His Leu Arg Ser
Cys Glu Tyr Lys Gly Arg Pro Pro Lys Ala Gly Ala 145 150 155 160 Glu
Pro Ala Ser Glu Arg Glu Val Ser 165 81 1193 DNA Homo sapiens CDS
(1)..(1171) 81 atg aaa cta att acc atc ctt ttc ctc tgc tcc agg cta
cta cta agt 48 Met Lys Leu Ile Thr Ile Leu Phe Leu Cys Ser Arg Leu
Leu Leu Ser 1 5 10 15 tta acc cag gaa tca cag tcc gag gaa att gac
tgc aat gac aag gat 96 Leu Thr Gln Glu Ser Gln Ser Glu Glu Ile Asp
Cys Asn Asp Lys Asp 20 25 30 tta ttt aaa gct gtg gat gct gct ctg
aag aaa tat aac agt caa aac 144 Leu Phe Lys Ala Val Asp Ala Ala Leu
Lys Lys Tyr Asn Ser Gln Asn 35 40 45 caa agt aac aac cag ttt gta
ttg tac cgc ata act gaa gcc act aag 192 Gln Ser Asn Asn Gln Phe Val
Leu Tyr Arg Ile Thr Glu Ala Thr Lys 50 55 60 acg gcc act gga gaa
tgc acg gca acc gtg ggg aag agg agc agt acg 240 Thr Ala Thr Gly Glu
Cys Thr Ala Thr Val Gly Lys Arg Ser Ser Thr 65 70 75 80 aaa ttc tcc
gtg gct acc cag acc tgc cag att act cca gcc gag ggc 288 Lys Phe Ser
Val Ala Thr Gln Thr Cys Gln Ile Thr Pro Ala Glu Gly 85 90 95 cct
gtg gtg aca gcc cag tac gac tgc ctc ggc tgt gtg cat cct ata 336 Pro
Val Val Thr Ala Gln Tyr Asp Cys Leu Gly Cys Val His Pro Ile 100 105
110 tca acg cag agc cca gac ctg gag ccc att ctg aga cac ggc att cag
384 Ser Thr Gln Ser Pro Asp Leu Glu Pro Ile Leu Arg His Gly Ile Gln
115 120 125 tac ttt aac aac aac act caa cat tcc tcc ctc ttc acg ctt
aat gaa 432 Tyr Phe Asn Asn Asn Thr Gln His Ser Ser Leu Phe Thr Leu
Asn Glu 130 135 140 gta aaa cgg gcc caa aga cag gtg gtg gct gga ttg
aac ttt cga att 480 Val Lys Arg Ala Gln Arg Gln Val Val Ala Gly Leu
Asn Phe Arg Ile 145 150 155 160 acc tac tca att gtg caa acg aat tgt
tcc aaa gag aat ttt ctg ttc 528 Thr Tyr Ser Ile Val Gln Thr Asn Cys
Ser Lys Glu Asn Phe Leu Phe 165 170 175 tta act cca gac tgc gag tcc
ctt tgg aat ggt gat acc ggt gaa tgt 576 Leu Thr Pro Asp Cys Glu Ser
Leu Trp Asn Gly Asp Thr Gly Glu Cys 180 185 190 aca gat aat gca tac
atc gat att cag cta cga att gct tcc ttc tca 624 Thr Asp Asn Ala Tyr
Ile Asp Ile Gln Leu Arg Ile Ala Ser Phe Ser 195 200 205 cag aac tgt
gac att tat cca ggg aag gat ttt gta caa cca cct acc 672 Gln Asn Cys
Asp Ile Tyr Pro Gly Lys Asp Phe Val Gln Pro Pro Thr 210 215 220 aag
att tgc gtg ggc tgc ccc aga gat ata ccc acc aac agc cca gag 720 Lys
Ile Cys Val Gly Cys Pro Arg Asp Ile Pro Thr Asn Ser Pro Glu 225 230
235 240 ctg gag gag aca ctg act cac acc atc aca aag ctt aat gca gag
aat 768 Leu Glu Glu Thr Leu Thr His Thr Ile Thr Lys Leu Asn Ala Glu
Asn 245 250 255 aac gca act ttc tat ttc aag att gac aat gtg aaa aaa
gca aga gta 816 Asn Ala Thr Phe Tyr Phe Lys Ile Asp Asn Val Lys Lys
Ala Arg Val 260 265 270 cag gtg gtg gct ggc aag aaa tat ttt att gac
ttc gtg gcc agg gaa 864 Gln Val Val Ala Gly Lys Lys Tyr Phe Ile Asp
Phe Val Ala Arg Glu 275 280 285 acc aca tgt tcc aag gaa agt aat gaa
gag ttg acc gaa agc tgt gag 912 Thr Thr Cys Ser Lys Glu Ser Asn Glu
Glu Leu Thr Glu Ser Cys Glu 290 295 300 acc aaa aaa ctt ggc caa agc
cta gat tgc aac gct gaa gtt tat gtg 960 Thr Lys Lys Leu Gly Gln Ser
Leu Asp Cys Asn Ala Glu Val Tyr Val 305 310 315 320 gta ccc tgg gag
aaa aaa att tac cct act gtc aac tgt caa cca ctg 1008 Val Pro Trp
Glu Lys Lys Ile Tyr Pro Thr Val Asn Cys Gln Pro Leu 325 330 335 gga
atg atc tca ctg atg aaa agg cct cca ggt ttt tca cct ttc cga 1056
Gly Met Ile Ser Leu Met Lys Arg Pro Pro Gly Phe Ser Pro Phe Arg 340
345 350 tca tca cga ata ggg gaa ata aaa gaa gaa aca act agt cac cta
agg 1104 Ser Ser Arg Ile Gly Glu Ile Lys Glu Glu Thr Thr Ser His
Leu Arg 355 360 365 tcc tgc gag tac aag ggt cga ccc cca aag gca ggg
gca gag cca gta 1152 Ser Cys Glu Tyr Lys Gly Arg Pro Pro Lys Ala
Gly Ala Glu Pro Val 370 375 380 tct gag agg gag gtc tct tgaccaatgg
gcagaatctt cac 1193 Ser Glu Arg Glu Val Ser 385 390 82 390 PRT Homo
sapiens 82 Met Lys Leu Ile Thr Ile Leu Phe Leu Cys Ser Arg Leu Leu
Leu Ser 1 5 10 15 Leu Thr Gln Glu Ser Gln Ser Glu Glu Ile Asp Cys
Asn Asp Lys Asp 20 25 30 Leu Phe Lys Ala Val Asp Ala Ala Leu Lys
Lys Tyr Asn Ser Gln Asn 35 40 45 Gln Ser Asn Asn Gln Phe Val Leu
Tyr Arg Ile Thr Glu Ala Thr Lys 50 55 60 Thr Ala Thr Gly Glu Cys
Thr Ala Thr Val Gly Lys Arg Ser Ser Thr 65 70 75 80 Lys Phe Ser Val
Ala Thr Gln Thr Cys Gln Ile Thr Pro Ala Glu Gly 85 90 95 Pro Val
Val Thr Ala Gln Tyr Asp Cys Leu Gly Cys Val His Pro Ile 100 105 110
Ser Thr Gln Ser Pro Asp Leu Glu Pro Ile Leu Arg His Gly Ile Gln 115
120 125 Tyr Phe Asn Asn Asn Thr Gln His Ser Ser Leu Phe Thr Leu Asn
Glu 130 135 140 Val Lys Arg Ala Gln Arg Gln Val Val Ala Gly Leu Asn
Phe Arg Ile 145 150 155 160 Thr Tyr Ser Ile Val Gln Thr Asn Cys Ser
Lys Glu Asn Phe Leu Phe 165 170 175 Leu Thr Pro Asp Cys Glu Ser Leu
Trp Asn Gly Asp Thr Gly Glu Cys 180 185 190 Thr Asp Asn Ala Tyr Ile
Asp Ile Gln Leu Arg Ile Ala Ser Phe Ser 195 200 205 Gln Asn Cys Asp
Ile Tyr Pro Gly Lys Asp Phe Val Gln Pro Pro Thr 210 215 220 Lys Ile
Cys Val Gly Cys Pro Arg Asp Ile Pro Thr Asn Ser Pro Glu 225 230 235
240 Leu Glu Glu Thr Leu Thr His Thr Ile Thr Lys Leu Asn Ala Glu Asn
245 250 255 Asn Ala Thr Phe Tyr Phe Lys Ile Asp Asn Val Lys Lys Ala
Arg Val 260 265 270 Gln Val Val Ala Gly Lys Lys Tyr Phe Ile Asp Phe
Val Ala Arg Glu 275 280 285 Thr Thr Cys Ser Lys Glu Ser Asn Glu Glu
Leu Thr Glu Ser Cys Glu 290 295 300 Thr Lys Lys Leu Gly Gln Ser Leu
Asp Cys Asn Ala Glu Val Tyr Val 305 310 315 320 Val Pro Trp Glu Lys
Lys Ile Tyr Pro Thr Val Asn Cys Gln Pro Leu 325 330 335 Gly Met Ile
Ser Leu Met Lys Arg Pro Pro Gly Phe Ser Pro Phe Arg 340 345 350 Ser
Ser Arg Ile Gly Glu Ile Lys Glu Glu Thr Thr Ser His Leu Arg 355 360
365 Ser Cys Glu Tyr Lys Gly Arg Pro Pro Lys Ala Gly Ala Glu Pro Val
370 375 380 Ser Glu Arg Glu Val Ser 385 390 83 1984 DNA Homo
sapiens CDS (50)..(1982) 83 aattccggtt gaaaccatcc ctcagctcct
agagggagat tgttagatc atg aaa 55 Met Lys 1 cta att acc atc ctt ttc
ctc tgc tcc agg cta cta cta agt tta acc 103 Leu Ile Thr Ile Leu Phe
Leu Cys Ser Arg Leu Leu Leu Ser Leu Thr 5 10 15 cag gaa tca cag tcc
gag gaa att gac tgc aat gac aag gat tta ttt 151 Gln Glu Ser Gln Ser
Glu Glu Ile Asp Cys Asn Asp Lys Asp Leu Phe 20 25 30 aaa gct gtg
gat gct gct ctg aag aaa tat aac agt caa aac caa agt 199 Lys Ala Val
Asp Ala Ala Leu Lys Lys Tyr Asn Ser Gln Asn Gln Ser 35 40 45 50 aac
aac cag ttt gta ttg tac cgc ata act gaa gcc act aag acg gtt 247 Asn
Asn Gln Phe Val Leu Tyr Arg Ile Thr Glu Ala Thr Lys Thr Val 55 60
65 ggc tct gac acg ttt tat tcc ttc aag tac gaa atc aag gag ggg gat
295 Gly Ser Asp Thr Phe Tyr Ser Phe Lys Tyr Glu Ile Lys Glu Gly Asp
70 75 80 tgt cct gtt caa agt ggc aaa acc tgg cag gac tgt gag tac
aag gat 343 Cys Pro Val Gln Ser Gly Lys Thr Trp Gln Asp Cys Glu Tyr
Lys Asp 85 90 95 gct gca aaa gca gcc act gga gaa tgc acg gca acc
gtg ggg aag agg 391 Ala Ala Lys Ala Ala Thr Gly Glu Cys Thr Ala Thr
Val Gly Lys Arg 100 105 110 agc agt acg aaa ttc tcc gtg gct acc cag
acc tgc cag att act cca 439 Ser Ser Thr Lys Phe Ser Val Ala Thr Gln
Thr Cys Gln Ile Thr Pro 115 120 125 130 gcc gag ggc cct gtg gtg aca
gcc cag tac gac tgc ctc ggc tgt gtg 487 Ala Glu Gly Pro Val Val Thr
Ala Gln Tyr Asp Cys Leu Gly Cys Val 135 140 145 cat cct ata tca acg
cag agc cca gac ctg gag ccc att ctg aga cac 535 His Pro Ile Ser Thr
Gln Ser Pro Asp Leu Glu Pro Ile Leu Arg His 150 155 160 ggc att cag
tac ttt aac aac aac act caa cat tcc tcc ctc ttc atg 583 Gly Ile Gln
Tyr Phe Asn Asn Asn Thr Gln His Ser Ser Leu Phe Met 165 170 175 ctt
aat gaa gta aaa cgg gcc caa aga cag gtg gtg gct gga ttg aac 631 Leu
Asn Glu Val Lys Arg Ala Gln Arg Gln Val Val Ala Gly Leu Asn 180 185
190 ttt cga att acc tac tca att gtg caa acg aat tgt tcc aaa gag aat
679 Phe Arg Ile Thr Tyr Ser Ile Val Gln Thr Asn Cys Ser Lys Glu Asn
195 200 205 210 ttt ctg ttc tta act cca gac tgc aag tcc ctt tgg aat
ggt gat acc 727 Phe Leu Phe Leu Thr Pro Asp Cys Lys Ser Leu Trp Asn
Gly Asp Thr 215 220 225 ggt gaa tgt aca gat aat gca tac atc gat att
cag cta cga att gct 775 Gly Glu Cys Thr Asp Asn Ala Tyr Ile Asp Ile
Gln Leu Arg Ile Ala 230 235 240 tcc ttc tca cag aac tgt gac att tat
cca ggg aag gat ttt gta caa 823 Ser Phe Ser Gln Asn Cys Asp Ile Tyr
Pro Gly Lys Asp Phe Val Gln 245 250 255 cca cct acc aag att tgc gtg
ggc tgc ccc aga gat ata ccc acc aac 871 Pro Pro Thr Lys Ile Cys Val
Gly Cys Pro Arg Asp Ile Pro Thr Asn 260 265 270 agc cca gag ctg gag
gag aca ctg act cac acc atc aca aag ctt aat 919 Ser Pro Glu Leu Glu
Glu Thr Leu Thr His Thr Ile Thr Lys Leu Asn 275 280 285 290 gca gag
aat aac gca act ttc tat ttc aag att gac aat gtg aaa aaa 967 Ala Glu
Asn Asn Ala Thr Phe Tyr Phe Lys Ile Asp Asn Val Lys Lys 295 300 305
gca aga gta cag gtg gtg gct ggc aag aaa tat ttt att gac ttc gtg
1015 Ala Arg Val Gln Val Val Ala Gly Lys Lys Tyr Phe Ile Asp Phe
Val 310 315 320 gcc agg gaa acc aca tgt tcc aag gaa agt aat gaa gag
ttg acc gaa 1063 Ala Arg Glu Thr Thr Cys Ser Lys Glu Ser Asn Glu
Glu Leu Thr Glu 325 330 335 agc tgt gag acc aaa aaa ctt ggc caa agc
cta gat tgc aac gct gaa 1111 Ser Cys Glu Thr Lys Lys Leu Gly Gln
Ser Leu Asp Cys Asn Ala Glu 340 345 350 gtt tat gtg gta ccc tgg gag
aaa aaa att tac cct act gtc aac tgt 1159 Val Tyr Val Val Pro Trp
Glu Lys Lys Ile Tyr Pro Thr Val Asn Cys 355 360 365 370 caa cca ctg
gga atg atc tca ctg atg aaa agg cct cca ggt ttt tca 1207 Gln Pro
Leu Gly Met Ile Ser Leu Met Lys Arg Pro Pro Gly
Phe Ser 375 380 385 cct ttc cga tca tca cga ata ggg gaa ata aaa gaa
gaa aca act gta 1255 Pro Phe Arg Ser Ser Arg Ile Gly Glu Ile Lys
Glu Glu Thr Thr Val 390 395 400 agt cca ccc cac act tcc atg gca cct
gca caa gat gaa gag cgg gat 1303 Ser Pro Pro His Thr Ser Met Ala
Pro Ala Gln Asp Glu Glu Arg Asp 405 410 415 tca gga aaa gaa caa ggg
cat act cgt aga cat gac tgg ggc cat gaa 1351 Ser Gly Lys Glu Gln
Gly His Thr Arg Arg His Asp Trp Gly His Glu 420 425 430 aaa caa aga
aaa cat aat ctt ggc cat ggc cat aaa cat gaa cgt gac 1399 Lys Gln
Arg Lys His Asn Leu Gly His Gly His Lys His Glu Arg Asp 435 440 445
450 caa ggg cat ggg cac caa aga gga cat ggc ctt ggc cat gga cac gaa
1447 Gln Gly His Gly His Gln Arg Gly His Gly Leu Gly His Gly His
Glu 455 460 465 caa cag cat ggt ctt ggt cat gga cat aag ttc aaa ctt
gat gat gat 1495 Gln Gln His Gly Leu Gly His Gly His Lys Phe Lys
Leu Asp Asp Asp 470 475 480 ctt gaa cac caa ggg ggc cat gtc ctt gac
cat gga cat aag cat aag 1543 Leu Glu His Gln Gly Gly His Val Leu
Asp His Gly His Lys His Lys 485 490 495 cat ggt cat ggc cac gga aaa
cat aaa aat aaa ggc aaa aag aat gga 1591 His Gly His Gly His Gly
Lys His Lys Asn Lys Gly Lys Lys Asn Gly 500 505 510 aag cac aat ggt
tgg aaa aca gag cat ttg gca agc tct tct gaa gac 1639 Lys His Asn
Gly Trp Lys Thr Glu His Leu Ala Ser Ser Ser Glu Asp 515 520 525 530
agt act aca cct tct gca cag aca caa gag aag aca gaa ggg cca aca
1687 Ser Thr Thr Pro Ser Ala Gln Thr Gln Glu Lys Thr Glu Gly Pro
Thr 535 540 545 ccc atc cct tcc cta gcc aag cca ggt gta aca gtt acc
ttt tct gac 1735 Pro Ile Pro Ser Leu Ala Lys Pro Gly Val Thr Val
Thr Phe Ser Asp 550 555 560 ttt cag gac tct gat ctc att gca act atg
atg cct cct ata tca cca 1783 Phe Gln Asp Ser Asp Leu Ile Ala Thr
Met Met Pro Pro Ile Ser Pro 565 570 575 gct ccc ata cag agt gat gac
gat tgg atc cct gat atc cag ata gac 1831 Ala Pro Ile Gln Ser Asp
Asp Asp Trp Ile Pro Asp Ile Gln Ile Asp 580 585 590 cca aat ggc ctt
tca ttt aac cca ata tca gat ttt cca gac acg acc 1879 Pro Asn Gly
Leu Ser Phe Asn Pro Ile Ser Asp Phe Pro Asp Thr Thr 595 600 605 610
tcc cca aaa tgt cct gga cgc ccc tgg aag tca gtt agt gaa att aat
1927 Ser Pro Lys Cys Pro Gly Arg Pro Trp Lys Ser Val Ser Glu Ile
Asn 615 620 625 cca acc aca caa atg aaa gaa tct tat tat ttc gat ctc
act gat ggc 1975 Pro Thr Thr Gln Met Lys Glu Ser Tyr Tyr Phe Asp
Leu Thr Asp Gly 630 635 640 ctt tct taa 1984 Leu Ser 84 644 PRT
Homo sapiens 84 Met Lys Leu Ile Thr Ile Leu Phe Leu Cys Ser Arg Leu
Leu Leu Ser 1 5 10 15 Leu Thr Gln Glu Ser Gln Ser Glu Glu Ile Asp
Cys Asn Asp Lys Asp 20 25 30 Leu Phe Lys Ala Val Asp Ala Ala Leu
Lys Lys Tyr Asn Ser Gln Asn 35 40 45 Gln Ser Asn Asn Gln Phe Val
Leu Tyr Arg Ile Thr Glu Ala Thr Lys 50 55 60 Thr Val Gly Ser Asp
Thr Phe Tyr Ser Phe Lys Tyr Glu Ile Lys Glu 65 70 75 80 Gly Asp Cys
Pro Val Gln Ser Gly Lys Thr Trp Gln Asp Cys Glu Tyr 85 90 95 Lys
Asp Ala Ala Lys Ala Ala Thr Gly Glu Cys Thr Ala Thr Val Gly 100 105
110 Lys Arg Ser Ser Thr Lys Phe Ser Val Ala Thr Gln Thr Cys Gln Ile
115 120 125 Thr Pro Ala Glu Gly Pro Val Val Thr Ala Gln Tyr Asp Cys
Leu Gly 130 135 140 Cys Val His Pro Ile Ser Thr Gln Ser Pro Asp Leu
Glu Pro Ile Leu 145 150 155 160 Arg His Gly Ile Gln Tyr Phe Asn Asn
Asn Thr Gln His Ser Ser Leu 165 170 175 Phe Met Leu Asn Glu Val Lys
Arg Ala Gln Arg Gln Val Val Ala Gly 180 185 190 Leu Asn Phe Arg Ile
Thr Tyr Ser Ile Val Gln Thr Asn Cys Ser Lys 195 200 205 Glu Asn Phe
Leu Phe Leu Thr Pro Asp Cys Lys Ser Leu Trp Asn Gly 210 215 220 Asp
Thr Gly Glu Cys Thr Asp Asn Ala Tyr Ile Asp Ile Gln Leu Arg 225 230
235 240 Ile Ala Ser Phe Ser Gln Asn Cys Asp Ile Tyr Pro Gly Lys Asp
Phe 245 250 255 Val Gln Pro Pro Thr Lys Ile Cys Val Gly Cys Pro Arg
Asp Ile Pro 260 265 270 Thr Asn Ser Pro Glu Leu Glu Glu Thr Leu Thr
His Thr Ile Thr Lys 275 280 285 Leu Asn Ala Glu Asn Asn Ala Thr Phe
Tyr Phe Lys Ile Asp Asn Val 290 295 300 Lys Lys Ala Arg Val Gln Val
Val Ala Gly Lys Lys Tyr Phe Ile Asp 305 310 315 320 Phe Val Ala Arg
Glu Thr Thr Cys Ser Lys Glu Ser Asn Glu Glu Leu 325 330 335 Thr Glu
Ser Cys Glu Thr Lys Lys Leu Gly Gln Ser Leu Asp Cys Asn 340 345 350
Ala Glu Val Tyr Val Val Pro Trp Glu Lys Lys Ile Tyr Pro Thr Val 355
360 365 Asn Cys Gln Pro Leu Gly Met Ile Ser Leu Met Lys Arg Pro Pro
Gly 370 375 380 Phe Ser Pro Phe Arg Ser Ser Arg Ile Gly Glu Ile Lys
Glu Glu Thr 385 390 395 400 Thr Val Ser Pro Pro His Thr Ser Met Ala
Pro Ala Gln Asp Glu Glu 405 410 415 Arg Asp Ser Gly Lys Glu Gln Gly
His Thr Arg Arg His Asp Trp Gly 420 425 430 His Glu Lys Gln Arg Lys
His Asn Leu Gly His Gly His Lys His Glu 435 440 445 Arg Asp Gln Gly
His Gly His Gln Arg Gly His Gly Leu Gly His Gly 450 455 460 His Glu
Gln Gln His Gly Leu Gly His Gly His Lys Phe Lys Leu Asp 465 470 475
480 Asp Asp Leu Glu His Gln Gly Gly His Val Leu Asp His Gly His Lys
485 490 495 His Lys His Gly His Gly His Gly Lys His Lys Asn Lys Gly
Lys Lys 500 505 510 Asn Gly Lys His Asn Gly Trp Lys Thr Glu His Leu
Ala Ser Ser Ser 515 520 525 Glu Asp Ser Thr Thr Pro Ser Ala Gln Thr
Gln Glu Lys Thr Glu Gly 530 535 540 Pro Thr Pro Ile Pro Ser Leu Ala
Lys Pro Gly Val Thr Val Thr Phe 545 550 555 560 Ser Asp Phe Gln Asp
Ser Asp Leu Ile Ala Thr Met Met Pro Pro Ile 565 570 575 Ser Pro Ala
Pro Ile Gln Ser Asp Asp Asp Trp Ile Pro Asp Ile Gln 580 585 590 Ile
Asp Pro Asn Gly Leu Ser Phe Asn Pro Ile Ser Asp Phe Pro Asp 595 600
605 Thr Thr Ser Pro Lys Cys Pro Gly Arg Pro Trp Lys Ser Val Ser Glu
610 615 620 Ile Asn Pro Thr Thr Gln Met Lys Glu Ser Tyr Tyr Phe Asp
Leu Thr 625 630 635 640 Asp Gly Leu Ser 85 1272 DNA Homo sapiens
CDS (220)..(1249) 85 cttccccagg actccaggag acataaaact tgaaacggga
gacttcgtgc 50 aaatcctgct ccggacgctg ctgaagctca gatttctccc
actgcctgca 100 cagggtgctg cctgctggcg aatgtgactc tcctcctgtt
cacccacaag 150 gctgattttt ccgtgttcct cctctggaaa gagcattgct
ttctctcttc 200 cagcacttta cctacattc atg tct ttc agg tgg ctg ctt ctc
tat tat 249 Met Ser Phe Arg Trp Leu Leu Leu Tyr Tyr 1 5 10 gct ctg
tgc ttc tcc ctg tca aag gct tca gcc cac acc gtg gag cta 297 Ala Leu
Cys Phe Ser Leu Ser Lys Ala Ser Ala His Thr Val Glu Leu 15 20 25
aac aat atg ttt ggc cag atc cag tcg cct ggt tat cca gac tcc tat 345
Asn Asn Met Phe Gly Gln Ile Gln Ser Pro Gly Tyr Pro Asp Ser Tyr 30
35 40 ccc agt gat tca gag gtg act tgg aat atc act gtc cca gat ggg
ttt 393 Pro Ser Asp Ser Glu Val Thr Trp Asn Ile Thr Val Pro Asp Gly
Phe 45 50 55 cgg atc aag ctt tac ttc atg cac ttc aac ttg gaa tcc
tcc tac ctt 441 Arg Ile Lys Leu Tyr Phe Met His Phe Asn Leu Glu Ser
Ser Tyr Leu 60 65 70 tgt gaa tat gac tat gtg aag gta gaa act gag
gac act tcg aga gtg 489 Cys Glu Tyr Asp Tyr Val Lys Val Glu Thr Glu
Asp Thr Ser Arg Val 75 80 85 90 cca aat gac aag tgg ttt ggg agt ggg
gcc ctg ctc tct gcg tcc tgg 537 Pro Asn Asp Lys Trp Phe Gly Ser Gly
Ala Leu Leu Ser Ala Ser Trp 95 100 105 atc ctc aca gca gct cat gtg
ctg cgc tcc cag cgt aga gac acc acg 585 Ile Leu Thr Ala Ala His Val
Leu Arg Ser Gln Arg Arg Asp Thr Thr 110 115 120 gtg ata cca gtc tcc
aag gag cat gtc acc gtc tac ctg ggc ttg cat 633 Val Ile Pro Val Ser
Lys Glu His Val Thr Val Tyr Leu Gly Leu His 125 130 135 gat gtg cga
gac aaa tcg ggg gca gtc aac agc tca gct gcc cga gtg 681 Asp Val Arg
Asp Lys Ser Gly Ala Val Asn Ser Ser Ala Ala Arg Val 140 145 150 gtg
ctc cac cca gac ttc aac atc caa aac tac aac cac gat ata gct 729 Val
Leu His Pro Asp Phe Asn Ile Gln Asn Tyr Asn His Asp Ile Ala 155 160
165 170 ctg gtg cag ctg cag gag cct gtg ccc ctg gga ccc cac gtt atg
cct 777 Leu Val Gln Leu Gln Glu Pro Val Pro Leu Gly Pro His Val Met
Pro 175 180 185 gtc tgc ctg cca agg ctt gag cct gaa ggc ccg gcc ccc
cac atg ctg 825 Val Cys Leu Pro Arg Leu Glu Pro Glu Gly Pro Ala Pro
His Met Leu 190 195 200 ggc ctg gtg gcc ggc tgg ggc atc tcc aat ccc
aat gtg aca gtg gat 873 Gly Leu Val Ala Gly Trp Gly Ile Ser Asn Pro
Asn Val Thr Val Asp 205 210 215 gag atc atc agc agt ggc aca cgg acc
ttg tca gat gtc ctg cag tat 921 Glu Ile Ile Ser Ser Gly Thr Arg Thr
Leu Ser Asp Val Leu Gln Tyr 220 225 230 gtc aag tta ccc gtg gtg cct
cac gct gag tgc aaa act agc tat gag 969 Val Lys Leu Pro Val Val Pro
His Ala Glu Cys Lys Thr Ser Tyr Glu 235 240 245 250 tcc cgc tcg ggc
aat tac agc gtc acg gag aac atg ttc tgt gct ggc 1017 Ser Arg Ser
Gly Asn Tyr Ser Val Thr Glu Asn Met Phe Cys Ala Gly 255 260 265 tac
tac gag ggc ggc aaa gac acg tgc ctt gga gat agc ggt ggg gcc 1065
Tyr Tyr Glu Gly Gly Lys Asp Thr Cys Leu Gly Asp Ser Gly Gly Ala 270
275 280 ttt gtc atc ttt gat gac ttg agc cag cgc tgg gtg gtg caa ggc
ctg 1113 Phe Val Ile Phe Asp Asp Leu Ser Gln Arg Trp Val Val Gln
Gly Leu 285 290 295 gtg tcc tgg ggg gga cct gaa gaa tgc ggc agc aag
cag gtc tat gga 1161 Val Ser Trp Gly Gly Pro Glu Glu Cys Gly Ser
Lys Gln Val Tyr Gly 300 305 310 gtc tac aca aag gtc tcc aat tac gtg
gac tgg gtg tgg gag cag atg 1209 Val Tyr Thr Lys Val Ser Asn Tyr
Val Asp Trp Val Trp Glu Gln Met 315 320 325 330 ggc tta cca caa agt
gtt gtg gag ccc cag gtg gaa cgg tgagctgact 1258 Gly Leu Pro Gln Ser
Val Val Glu Pro Gln Val Glu Arg 335 340 tacttcctcg cggg 1272 86 343
PRT Homo sapiens 86 Met Ser Phe Arg Trp Leu Leu Leu Tyr Tyr Ala Leu
Cys Phe Ser Leu 1 5 10 15 Ser Lys Ala Ser Ala His Thr Val Glu Leu
Asn Asn Met Phe Gly Gln 20 25 30 Ile Gln Ser Pro Gly Tyr Pro Asp
Ser Tyr Pro Ser Asp Ser Glu Val 35 40 45 Thr Trp Asn Ile Thr Val
Pro Asp Gly Phe Arg Ile Lys Leu Tyr Phe 50 55 60 Met His Phe Asn
Leu Glu Ser Ser Tyr Leu Cys Glu Tyr Asp Tyr Val 65 70 75 80 Lys Val
Glu Thr Glu Asp Thr Ser Arg Val Pro Asn Asp Lys Trp Phe 85 90 95
Gly Ser Gly Ala Leu Leu Ser Ala Ser Trp Ile Leu Thr Ala Ala His 100
105 110 Val Leu Arg Ser Gln Arg Arg Asp Thr Thr Val Ile Pro Val Ser
Lys 115 120 125 Glu His Val Thr Val Tyr Leu Gly Leu His Asp Val Arg
Asp Lys Ser 130 135 140 Gly Ala Val Asn Ser Ser Ala Ala Arg Val Val
Leu His Pro Asp Phe 145 150 155 160 Asn Ile Gln Asn Tyr Asn His Asp
Ile Ala Leu Val Gln Leu Gln Glu 165 170 175 Pro Val Pro Leu Gly Pro
His Val Met Pro Val Cys Leu Pro Arg Leu 180 185 190 Glu Pro Glu Gly
Pro Ala Pro His Met Leu Gly Leu Val Ala Gly Trp 195 200 205 Gly Ile
Ser Asn Pro Asn Val Thr Val Asp Glu Ile Ile Ser Ser Gly 210 215 220
Thr Arg Thr Leu Ser Asp Val Leu Gln Tyr Val Lys Leu Pro Val Val 225
230 235 240 Pro His Ala Glu Cys Lys Thr Ser Tyr Glu Ser Arg Ser Gly
Asn Tyr 245 250 255 Ser Val Thr Glu Asn Met Phe Cys Ala Gly Tyr Tyr
Glu Gly Gly Lys 260 265 270 Asp Thr Cys Leu Gly Asp Ser Gly Gly Ala
Phe Val Ile Phe Asp Asp 275 280 285 Leu Ser Gln Arg Trp Val Val Gln
Gly Leu Val Ser Trp Gly Gly Pro 290 295 300 Glu Glu Cys Gly Ser Lys
Gln Val Tyr Gly Val Tyr Thr Lys Val Ser 305 310 315 320 Asn Tyr Val
Asp Trp Val Trp Glu Gln Met Gly Leu Pro Gln Ser Val 325 330 335 Val
Glu Pro Gln Val Glu Arg 340 87 861 DNA Homo sapiens CDS (10)..(775)
87 cagctcagc atg gct agg gta ctg gga gca ccc gtt gca ctg ggg ttg 48
Met Ala Arg Val Leu Gly Ala Pro Val Ala Leu Gly Leu 1 5 10 tgg agc
cta tgc tgg tct ctg gcc att gcc acc cct ctt cct ccg act 96 Trp Ser
Leu Cys Trp Ser Leu Ala Ile Ala Thr Pro Leu Pro Pro Thr 15 20 25
agt gcc cat ggg aat gtt gct gaa ggc gag acc aag cca gac cca gac 144
Ser Ala His Gly Asn Val Ala Glu Gly Glu Thr Lys Pro Asp Pro Asp 30
35 40 45 gtg act gaa cgc tgc tca gat ggc tgg agc ttt gat gct acc
acc ctg 192 Val Thr Glu Arg Cys Ser Asp Gly Trp Ser Phe Asp Ala Thr
Thr Leu 50 55 60 gat gac aat gga acc atg ctg ttt ttt aaa ggg acc
cac tac tgg cgt 240 Asp Asp Asn Gly Thr Met Leu Phe Phe Lys Gly Thr
His Tyr Trp Arg 65 70 75 ctg gac acc agc cgg gat ggc tgg cat agc
tgg ccc att gct cat cag 288 Leu Asp Thr Ser Arg Asp Gly Trp His Ser
Trp Pro Ile Ala His Gln 80 85 90 tgg ccc cag ggt cct tca gca gtg
gat gct gcc ttt tcc tgg gaa gaa 336 Trp Pro Gln Gly Pro Ser Ala Val
Asp Ala Ala Phe Ser Trp Glu Glu 95 100 105 aaa ctc tat ctg gtc cag
ggc acc cag gta tat gtc ttc ctg aca aag 384 Lys Leu Tyr Leu Val Gln
Gly Thr Gln Val Tyr Val Phe Leu Thr Lys 110 115 120 125 gga ggc tat
acc cta gta agc ggt tat ccg aag cgg ctg gag aag gaa 432 Gly Gly Tyr
Thr Leu Val Ser Gly Tyr Pro Lys Arg Leu Glu Lys Glu 130 135 140 gtc
ggg acc cct cat ggg att atc ctg gac tct gtg gat gcg gcc ttt 480 Val
Gly Thr Pro His Gly Ile Ile Leu Asp Ser Val Asp Ala Ala Phe 145 150
155 atc tgc cct ggg tct tct cgg ctc cat atc atg gca gga cgg cgg ctg
528 Ile Cys Pro Gly Ser Ser Arg Leu His Ile Met Ala Gly Arg Arg Leu
160 165 170 tgg tgg ctg gac ctg aag tca gga gcc caa gcc acg tgg aca
gag ctt 576 Trp Trp Leu Asp Leu Lys Ser Gly Ala Gln Ala Thr Trp Thr
Glu Leu 175 180 185 cct tgg ccc cat gag aag gta gac gga gcc ttg tgt
atg gaa aag tcc 624 Pro Trp Pro His Glu Lys Val Asp Gly Ala Leu Cys
Met Glu Lys Ser 190 195 200 205 ctt ggc cct aac tca tgt tcc gcc aat
ggt ccc ggc ttg tac ctc atc 672 Leu Gly Pro Asn Ser Cys Ser Ala Asn
Gly Pro Gly Leu Tyr Leu Ile 210 215 220 cat ggt ccc aat ttg tac tgc
tac agt gat gtg gag aaa ctg aat gca 720 His Gly Pro Asn Leu Tyr Cys
Tyr Ser Asp Val Glu Lys Leu Asn Ala 225 230 235 gcc aag gcc ctt ccg
caa ccc cag aat gtg acc agt ctc ctg ggc tgc 768 Ala Lys Ala Leu Pro
Gln
Pro Gln Asn Val Thr Ser Leu Leu Gly Cys 240 245 250 act cac
tgaggggcct tctgacatga gtctggcctg gccccacctc ctagttcctc 824 Thr His
255 ataataaaga cagattgctt cttcgcttct cactgag 861 88 255 PRT Homo
sapiens 88 Met Ala Arg Val Leu Gly Ala Pro Val Ala Leu Gly Leu Trp
Ser Leu 1 5 10 15 Cys Trp Ser Leu Ala Ile Ala Thr Pro Leu Pro Pro
Thr Ser Ala His 20 25 30 Gly Asn Val Ala Glu Gly Glu Thr Lys Pro
Asp Pro Asp Val Thr Glu 35 40 45 Arg Cys Ser Asp Gly Trp Ser Phe
Asp Ala Thr Thr Leu Asp Asp Asn 50 55 60 Gly Thr Met Leu Phe Phe
Lys Gly Thr His Tyr Trp Arg Leu Asp Thr 65 70 75 80 Ser Arg Asp Gly
Trp His Ser Trp Pro Ile Ala His Gln Trp Pro Gln 85 90 95 Gly Pro
Ser Ala Val Asp Ala Ala Phe Ser Trp Glu Glu Lys Leu Tyr 100 105 110
Leu Val Gln Gly Thr Gln Val Tyr Val Phe Leu Thr Lys Gly Gly Tyr 115
120 125 Thr Leu Val Ser Gly Tyr Pro Lys Arg Leu Glu Lys Glu Val Gly
Thr 130 135 140 Pro His Gly Ile Ile Leu Asp Ser Val Asp Ala Ala Phe
Ile Cys Pro 145 150 155 160 Gly Ser Ser Arg Leu His Ile Met Ala Gly
Arg Arg Leu Trp Trp Leu 165 170 175 Asp Leu Lys Ser Gly Ala Gln Ala
Thr Trp Thr Glu Leu Pro Trp Pro 180 185 190 His Glu Lys Val Asp Gly
Ala Leu Cys Met Glu Lys Ser Leu Gly Pro 195 200 205 Asn Ser Cys Ser
Ala Asn Gly Pro Gly Leu Tyr Leu Ile His Gly Pro 210 215 220 Asn Leu
Tyr Cys Tyr Ser Asp Val Glu Lys Leu Asn Ala Ala Lys Ala 225 230 235
240 Leu Pro Gln Pro Gln Asn Val Thr Ser Leu Leu Gly Cys Thr His 245
250 255 89 2671 DNA Homo sapiens CDS (15)..(2652) 89 cccgccgggc
gagc atg ggg cgc ctg gcc tcg agg ccg ctg ctg ctg gcg 50 Met Gly Arg
Leu Ala Ser Arg Pro Leu Leu Leu Ala 1 5 10 ctc ctg tcg ttg gct ctt
tgc cga ggg cgt gtg gtg aga gtc ccc aca 98 Leu Leu Ser Leu Ala Leu
Cys Arg Gly Arg Val Val Arg Val Pro Thr 15 20 25 gcg acc ctg gtt
cga gtg gtg ggc act gag ctg gtc atc ccc tgc aac 146 Ala Thr Leu Val
Arg Val Val Gly Thr Glu Leu Val Ile Pro Cys Asn 30 35 40 gtc agt
gac tat gat ggc ccc agc gag caa aac ttt gac tgg agc ttc 194 Val Ser
Asp Tyr Asp Gly Pro Ser Glu Gln Asn Phe Asp Trp Ser Phe 45 50 55 60
tca tct ttg ggg agc agc ttt gtg gag ctt gca agc acc tgg gag gtg 242
Ser Ser Leu Gly Ser Ser Phe Val Glu Leu Ala Ser Thr Trp Glu Val 65
70 75 ggg ttc cca gcc caa ctg tac cag gag cgg ctg cag agg ggc gag
atc 290 Gly Phe Pro Ala Gln Leu Tyr Gln Glu Arg Leu Gln Arg Gly Glu
Ile 80 85 90 ctg tta agg cgg act gcc aac gac gcc gtg gag ctc cac
ata aag aac 338 Leu Leu Arg Arg Thr Ala Asn Asp Ala Val Glu Leu His
Ile Lys Asn 95 100 105 gtc cag cct tca gac caa ggc cac tac aaa tgt
tca acc ccc agc aca 386 Val Gln Pro Ser Asp Gln Gly His Tyr Lys Cys
Ser Thr Pro Ser Thr 110 115 120 gat gcc act gtc cag gga aac tat gag
gac aca gtg cag gtt aaa gtg 434 Asp Ala Thr Val Gln Gly Asn Tyr Glu
Asp Thr Val Gln Val Lys Val 125 130 135 140 ctg gcc gac tcc ctg cac
gtg ggc ccc agc gcg cgg ccc ccg ccg agc 482 Leu Ala Asp Ser Leu His
Val Gly Pro Ser Ala Arg Pro Pro Pro Ser 145 150 155 ctg agc ctg cgg
gag ggg gag ccc ttc gag ctg cgc tgc acc gcc gcc 530 Leu Ser Leu Arg
Glu Gly Glu Pro Phe Glu Leu Arg Cys Thr Ala Ala 160 165 170 tcc gcc
tcg ccg ctg cac acg cac ctg gcg ctg ctg tgg gag gtg cac 578 Ser Ala
Ser Pro Leu His Thr His Leu Ala Leu Leu Trp Glu Val His 175 180 185
cgc ggc ccg gcc agg cgg agc gtc ctc gcc ctg acc cac gag ggc agg 626
Arg Gly Pro Ala Arg Arg Ser Val Leu Ala Leu Thr His Glu Gly Arg 190
195 200 ttc cac ccg ggc ctg ggg tac gag cag cgc tac cac agt ggg gac
gtg 674 Phe His Pro Gly Leu Gly Tyr Glu Gln Arg Tyr His Ser Gly Asp
Val 205 210 215 220 cgc ctc gac acc gtg ggc agc gac gcc tac cgc ctc
tca gtg tcc cgg 722 Arg Leu Asp Thr Val Gly Ser Asp Ala Tyr Arg Leu
Ser Val Ser Arg 225 230 235 gct ctg tct gcc gac cag ggc tcc tac agg
tgt atc gtc agc gag tgg 770 Ala Leu Ser Ala Asp Gln Gly Ser Tyr Arg
Cys Ile Val Ser Glu Trp 240 245 250 atc gcc gag cag ggc aac tgg cag
gaa atc caa gaa aag gcc gtg gaa 818 Ile Ala Glu Gln Gly Asn Trp Gln
Glu Ile Gln Glu Lys Ala Val Glu 255 260 265 gtt gcc acc gtg gtg atc
cag ccg aca gtt ctg cga gca gcc gtg ccc 866 Val Ala Thr Val Val Ile
Gln Pro Thr Val Leu Arg Ala Ala Val Pro 270 275 280 aag aat gtg tct
gtg gct gaa gga aag gaa ctg gac ctg acc tgt aac 914 Lys Asn Val Ser
Val Ala Glu Gly Lys Glu Leu Asp Leu Thr Cys Asn 285 290 295 300 atc
aca aca gac cga gcc gat gac gtc cgg ccc gag gtg acg tgg tcc 962 Ile
Thr Thr Asp Arg Ala Asp Asp Val Arg Pro Glu Val Thr Trp Ser 305 310
315 ttc agc agg atg cct gac agc acc cta cct ggc tcc cgc gtg ttg gcg
1010 Phe Ser Arg Met Pro Asp Ser Thr Leu Pro Gly Ser Arg Val Leu
Ala 320 325 330 cgg ctt gac cgt gat tcc ctg gtg cac agc tcg cct cat
gtt gct ttg 1058 Arg Leu Asp Arg Asp Ser Leu Val His Ser Ser Pro
His Val Ala Leu 335 340 345 agt cat gtg gat gca cgc tcc tac cat tta
ctg gtt cgg gat gtt agc 1106 Ser His Val Asp Ala Arg Ser Tyr His
Leu Leu Val Arg Asp Val Ser 350 355 360 aaa gaa aac tct ggc tac tat
tac tgc cac gtg tcc ctg tgg gca ccc 1154 Lys Glu Asn Ser Gly Tyr
Tyr Tyr Cys His Val Ser Leu Trp Ala Pro 365 370 375 380 gga cac aac
agg agc tgg cac aaa gtg gca gag gcc gtg tct tcc cca 1202 Gly His
Asn Arg Ser Trp His Lys Val Ala Glu Ala Val Ser Ser Pro 385 390 395
gct ggt gtg ggt gtg acc tgg cta gaa cca gac tac cag gtg tac ctg
1250 Ala Gly Val Gly Val Thr Trp Leu Glu Pro Asp Tyr Gln Val Tyr
Leu 400 405 410 aat gct tcc aag gtc ccc ggg ttt gcg gat gac ccc aca
gag ctg gca 1298 Asn Ala Ser Lys Val Pro Gly Phe Ala Asp Asp Pro
Thr Glu Leu Ala 415 420 425 tgc cgg gtg gtg gac acg aag agt ggg gag
gcg aat gtc cga ttc acg 1346 Cys Arg Val Val Asp Thr Lys Ser Gly
Glu Ala Asn Val Arg Phe Thr 430 435 440 gtt tcg tgg tac tac agg atg
aac cgg cgc agc gac aat gtg gtg acc 1394 Val Ser Trp Tyr Tyr Arg
Met Asn Arg Arg Ser Asp Asn Val Val Thr 445 450 455 460 agc gag ctg
ctt gca gtc atg gac ggg gac tgg acg cta aaa tat gga 1442 Ser Glu
Leu Leu Ala Val Met Asp Gly Asp Trp Thr Leu Lys Tyr Gly 465 470 475
gag agg agc aag cag cgg gcc cag gat gga gac ttt att ttt tct aag
1490 Glu Arg Ser Lys Gln Arg Ala Gln Asp Gly Asp Phe Ile Phe Ser
Lys 480 485 490 gaa cat aca gac acg ttc aat ttc cgg atc caa agg act
aca gag gaa 1538 Glu His Thr Asp Thr Phe Asn Phe Arg Ile Gln Arg
Thr Thr Glu Glu 495 500 505 gac aga ggc aat tat tac tgt gtt gtg tct
gcc tgg acc aaa cag cgg 1586 Asp Arg Gly Asn Tyr Tyr Cys Val Val
Ser Ala Trp Thr Lys Gln Arg 510 515 520 aac aac agc tgg gtg aaa agc
aag gat gtc ttc tcc aag cct gtt aac 1634 Asn Asn Ser Trp Val Lys
Ser Lys Asp Val Phe Ser Lys Pro Val Asn 525 530 535 540 ata ttt tgg
gca tta gaa gat tcc gtg ctt gtg gtg aag gcg agg cag 1682 Ile Phe
Trp Ala Leu Glu Asp Ser Val Leu Val Val Lys Ala Arg Gln 545 550 555
cca aag cct ttc ttt gct gcc gga aat aca ttt gag atg act tgc aaa
1730 Pro Lys Pro Phe Phe Ala Ala Gly Asn Thr Phe Glu Met Thr Cys
Lys 560 565 570 gta tct tcc aag aat att aag tcg cca cgc tac tct gtt
ctc atc atg 1778 Val Ser Ser Lys Asn Ile Lys Ser Pro Arg Tyr Ser
Val Leu Ile Met 575 580 585 gct gag aag cct gtc ggc gac ctc tcc agt
ccc aat gaa acg aag tac 1826 Ala Glu Lys Pro Val Gly Asp Leu Ser
Ser Pro Asn Glu Thr Lys Tyr 590 595 600 atc atc tct ctg gac cag gat
tct gtg gtg aag ctg gag aat tgg aca 1874 Ile Ile Ser Leu Asp Gln
Asp Ser Val Val Lys Leu Glu Asn Trp Thr 605 610 615 620 gat gca tca
cgg gtg gat ggc gtt gtt tta gaa aaa gtg cag gag gat 1922 Asp Ala
Ser Arg Val Asp Gly Val Val Leu Glu Lys Val Gln Glu Asp 625 630 635
gag ttc cgc tat cga atg tac cag act cag gtc tca gac gca ggg ctg
1970 Glu Phe Arg Tyr Arg Met Tyr Gln Thr Gln Val Ser Asp Ala Gly
Leu 640 645 650 tac cgc tgc atg gtg aca gcc tgg tct cct gtc agg ggc
agc ctt tgg 2018 Tyr Arg Cys Met Val Thr Ala Trp Ser Pro Val Arg
Gly Ser Leu Trp 655 660 665 cga gaa gca gca acc agt ctc tcc aat cct
att gag ata gac ttc caa 2066 Arg Glu Ala Ala Thr Ser Leu Ser Asn
Pro Ile Glu Ile Asp Phe Gln 670 675 680 acc tca ggt cct ata ttt aat
gct tct gtg cat tca gac aca cca tca 2114 Thr Ser Gly Pro Ile Phe
Asn Ala Ser Val His Ser Asp Thr Pro Ser 685 690 695 700 gta att cgg
gga gat ctg atc aaa ttg ttc tgt atc atc act gtc gag 2162 Val Ile
Arg Gly Asp Leu Ile Lys Leu Phe Cys Ile Ile Thr Val Glu 705 710 715
gga gca gca ctg gat cca gat gac atg gcc ttt gat gtg tcc tgg ttt
2210 Gly Ala Ala Leu Asp Pro Asp Asp Met Ala Phe Asp Val Ser Trp
Phe 720 725 730 gcg gtg cac tct ttt ggc ctg gac aag gct cct gtg ctc
ctg tct tcc 2258 Ala Val His Ser Phe Gly Leu Asp Lys Ala Pro Val
Leu Leu Ser Ser 735 740 745 ctg gat cgg aag ggc atc gtg acc acc tcc
cgg agg gac tgg aag agc 2306 Leu Asp Arg Lys Gly Ile Val Thr Thr
Ser Arg Arg Asp Trp Lys Ser 750 755 760 gac ctc agc ctg gag cgc gtg
agt gtg ctg gaa ttc ttg ctg caa gtg 2354 Asp Leu Ser Leu Glu Arg
Val Ser Val Leu Glu Phe Leu Leu Gln Val 765 770 775 780 cat ggc tcc
gag gac cag gac ttt ggc aac tac tac tgt tcc gtg act 2402 His Gly
Ser Glu Asp Gln Asp Phe Gly Asn Tyr Tyr Cys Ser Val Thr 785 790 795
cca tgg gtg aag tca cca aca ggt tcc tgg cag aag gag gca gag atc
2450 Pro Trp Val Lys Ser Pro Thr Gly Ser Trp Gln Lys Glu Ala Glu
Ile 800 805 810 cac tcc aag ccc gtt ttt ata act gtg aag atg gat gtg
ctg aac gcc 2498 His Ser Lys Pro Val Phe Ile Thr Val Lys Met Asp
Val Leu Asn Ala 815 820 825 ttc aag tat ccc ttg ctg atc ggc gtc ggt
ctg tcc acg gtc atc ggg 2546 Phe Lys Tyr Pro Leu Leu Ile Gly Val
Gly Leu Ser Thr Val Ile Gly 830 835 840 ctc ctg tcc tgt ctc atc ggg
tac tgc agc tcc cac tgg tgt tgt aag 2594 Leu Leu Ser Cys Leu Ile
Gly Tyr Cys Ser Ser His Trp Cys Cys Lys 845 850 855 860 aag gag gtt
cag gag aca cgg cgc gag cgc cgc agg ctc atg tcg atg 2642 Lys Glu
Val Gln Glu Thr Arg Arg Glu Arg Arg Arg Leu Met Ser Met 865 870 875
gag atg gac taggctggcc cgggagggga 2671 Glu Met Asp 90 879 PRT Homo
sapiens 90 Met Gly Arg Leu Ala Ser Arg Pro Leu Leu Leu Ala Leu Leu
Ser Leu 1 5 10 15 Ala Leu Cys Arg Gly Arg Val Val Arg Val Pro Thr
Ala Thr Leu Val 20 25 30 Arg Val Val Gly Thr Glu Leu Val Ile Pro
Cys Asn Val Ser Asp Tyr 35 40 45 Asp Gly Pro Ser Glu Gln Asn Phe
Asp Trp Ser Phe Ser Ser Leu Gly 50 55 60 Ser Ser Phe Val Glu Leu
Ala Ser Thr Trp Glu Val Gly Phe Pro Ala 65 70 75 80 Gln Leu Tyr Gln
Glu Arg Leu Gln Arg Gly Glu Ile Leu Leu Arg Arg 85 90 95 Thr Ala
Asn Asp Ala Val Glu Leu His Ile Lys Asn Val Gln Pro Ser 100 105 110
Asp Gln Gly His Tyr Lys Cys Ser Thr Pro Ser Thr Asp Ala Thr Val 115
120 125 Gln Gly Asn Tyr Glu Asp Thr Val Gln Val Lys Val Leu Ala Asp
Ser 130 135 140 Leu His Val Gly Pro Ser Ala Arg Pro Pro Pro Ser Leu
Ser Leu Arg 145 150 155 160 Glu Gly Glu Pro Phe Glu Leu Arg Cys Thr
Ala Ala Ser Ala Ser Pro 165 170 175 Leu His Thr His Leu Ala Leu Leu
Trp Glu Val His Arg Gly Pro Ala 180 185 190 Arg Arg Ser Val Leu Ala
Leu Thr His Glu Gly Arg Phe His Pro Gly 195 200 205 Leu Gly Tyr Glu
Gln Arg Tyr His Ser Gly Asp Val Arg Leu Asp Thr 210 215 220 Val Gly
Ser Asp Ala Tyr Arg Leu Ser Val Ser Arg Ala Leu Ser Ala 225 230 235
240 Asp Gln Gly Ser Tyr Arg Cys Ile Val Ser Glu Trp Ile Ala Glu Gln
245 250 255 Gly Asn Trp Gln Glu Ile Gln Glu Lys Ala Val Glu Val Ala
Thr Val 260 265 270 Val Ile Gln Pro Thr Val Leu Arg Ala Ala Val Pro
Lys Asn Val Ser 275 280 285 Val Ala Glu Gly Lys Glu Leu Asp Leu Thr
Cys Asn Ile Thr Thr Asp 290 295 300 Arg Ala Asp Asp Val Arg Pro Glu
Val Thr Trp Ser Phe Ser Arg Met 305 310 315 320 Pro Asp Ser Thr Leu
Pro Gly Ser Arg Val Leu Ala Arg Leu Asp Arg 325 330 335 Asp Ser Leu
Val His Ser Ser Pro His Val Ala Leu Ser His Val Asp 340 345 350 Ala
Arg Ser Tyr His Leu Leu Val Arg Asp Val Ser Lys Glu Asn Ser 355 360
365 Gly Tyr Tyr Tyr Cys His Val Ser Leu Trp Ala Pro Gly His Asn Arg
370 375 380 Ser Trp His Lys Val Ala Glu Ala Val Ser Ser Pro Ala Gly
Val Gly 385 390 395 400 Val Thr Trp Leu Glu Pro Asp Tyr Gln Val Tyr
Leu Asn Ala Ser Lys 405 410 415 Val Pro Gly Phe Ala Asp Asp Pro Thr
Glu Leu Ala Cys Arg Val Val 420 425 430 Asp Thr Lys Ser Gly Glu Ala
Asn Val Arg Phe Thr Val Ser Trp Tyr 435 440 445 Tyr Arg Met Asn Arg
Arg Ser Asp Asn Val Val Thr Ser Glu Leu Leu 450 455 460 Ala Val Met
Asp Gly Asp Trp Thr Leu Lys Tyr Gly Glu Arg Ser Lys 465 470 475 480
Gln Arg Ala Gln Asp Gly Asp Phe Ile Phe Ser Lys Glu His Thr Asp 485
490 495 Thr Phe Asn Phe Arg Ile Gln Arg Thr Thr Glu Glu Asp Arg Gly
Asn 500 505 510 Tyr Tyr Cys Val Val Ser Ala Trp Thr Lys Gln Arg Asn
Asn Ser Trp 515 520 525 Val Lys Ser Lys Asp Val Phe Ser Lys Pro Val
Asn Ile Phe Trp Ala 530 535 540 Leu Glu Asp Ser Val Leu Val Val Lys
Ala Arg Gln Pro Lys Pro Phe 545 550 555 560 Phe Ala Ala Gly Asn Thr
Phe Glu Met Thr Cys Lys Val Ser Ser Lys 565 570 575 Asn Ile Lys Ser
Pro Arg Tyr Ser Val Leu Ile Met Ala Glu Lys Pro 580 585 590 Val Gly
Asp Leu Ser Ser Pro Asn Glu Thr Lys Tyr Ile Ile Ser Leu 595 600 605
Asp Gln Asp Ser Val Val Lys Leu Glu Asn Trp Thr Asp Ala Ser Arg 610
615 620 Val Asp Gly Val Val Leu Glu Lys Val Gln Glu Asp Glu Phe Arg
Tyr 625 630 635 640 Arg Met Tyr Gln Thr Gln Val Ser Asp Ala Gly Leu
Tyr Arg Cys Met 645 650 655 Val Thr Ala Trp Ser Pro Val Arg Gly Ser
Leu Trp Arg Glu Ala Ala 660 665 670 Thr Ser Leu Ser Asn Pro Ile Glu
Ile Asp Phe Gln Thr Ser Gly Pro 675 680 685 Ile Phe Asn Ala Ser Val
His Ser Asp Thr Pro Ser Val Ile Arg Gly 690 695 700 Asp Leu Ile Lys
Leu Phe Cys Ile Ile Thr Val Glu Gly Ala Ala Leu 705 710 715
720 Asp Pro Asp Asp Met Ala Phe Asp Val Ser Trp Phe Ala Val His Ser
725 730 735 Phe Gly Leu Asp Lys Ala Pro Val Leu Leu Ser Ser Leu Asp
Arg Lys 740 745 750 Gly Ile Val Thr Thr Ser Arg Arg Asp Trp Lys Ser
Asp Leu Ser Leu 755 760 765 Glu Arg Val Ser Val Leu Glu Phe Leu Leu
Gln Val His Gly Ser Glu 770 775 780 Asp Gln Asp Phe Gly Asn Tyr Tyr
Cys Ser Val Thr Pro Trp Val Lys 785 790 795 800 Ser Pro Thr Gly Ser
Trp Gln Lys Glu Ala Glu Ile His Ser Lys Pro 805 810 815 Val Phe Ile
Thr Val Lys Met Asp Val Leu Asn Ala Phe Lys Tyr Pro 820 825 830 Leu
Leu Ile Gly Val Gly Leu Ser Thr Val Ile Gly Leu Leu Ser Cys 835 840
845 Leu Ile Gly Tyr Cys Ser Ser His Trp Cys Cys Lys Lys Glu Val Gln
850 855 860 Glu Thr Arg Arg Glu Arg Arg Arg Leu Met Ser Met Glu Met
Asp 865 870 875 91 1565 DNA Homo sapiens CDS (4)..(1549) 91 gga atg
ctc tcc cgc ctg agc ctg ctc cag gaa ttg gac ctc agc tac 48 Met Leu
Ser Arg Leu Ser Leu Leu Gln Glu Leu Asp Leu Ser Tyr 1 5 10 15 aac
cag ctc tca acc ctt gag cct ggg gcc ttc cat ggc cta caa agc 96 Asn
Gln Leu Ser Thr Leu Glu Pro Gly Ala Phe His Gly Leu Gln Ser 20 25
30 cta ctc acc ctg agg ctg cag ggc aat cgg ctc aga atc atg ggg cct
144 Leu Leu Thr Leu Arg Leu Gln Gly Asn Arg Leu Arg Ile Met Gly Pro
35 40 45 ggg gtc ttc tca ggc ctc tct gct ctg acc ctg ctg gac ctc
cgc ctc 192 Gly Val Phe Ser Gly Leu Ser Ala Leu Thr Leu Leu Asp Leu
Arg Leu 50 55 60 aac cag att gtt ctc ttc cta gat gga gct ttt ggg
gag cta ggc agc 240 Asn Gln Ile Val Leu Phe Leu Asp Gly Ala Phe Gly
Glu Leu Gly Ser 65 70 75 ctc cag aag ctg gag gtt ggg gac aac cac
ctg gta ttt gtg gct ccg 288 Leu Gln Lys Leu Glu Val Gly Asp Asn His
Leu Val Phe Val Ala Pro 80 85 90 95 ggg gcc ttt gca ggg cta gcc aag
ttg agc acc ctc acc ctg gag cgc 336 Gly Ala Phe Ala Gly Leu Ala Lys
Leu Ser Thr Leu Thr Leu Glu Arg 100 105 110 tgc aac ctc agc aca gtg
cct ggc cta gcc ctt gcc cgt ctc ccg gca 384 Cys Asn Leu Ser Thr Val
Pro Gly Leu Ala Leu Ala Arg Leu Pro Ala 115 120 125 cta gtg gcc cta
agg ctt aga gaa ctg gat att ggg agg ctg cca gct 432 Leu Val Ala Leu
Arg Leu Arg Glu Leu Asp Ile Gly Arg Leu Pro Ala 130 135 140 ggg gcc
ctg cgg ggg ctg ggg cag ctc aag gag ctg gag atc cac ctc 480 Gly Ala
Leu Arg Gly Leu Gly Gln Leu Lys Glu Leu Glu Ile His Leu 145 150 155
tgg cca tct ctg gag gct ctg gac cct ggg agc ctg gtt ggg ctc aat 528
Trp Pro Ser Leu Glu Ala Leu Asp Pro Gly Ser Leu Val Gly Leu Asn 160
165 170 175 ctc agc agc ctg gcc atc act cgc tgc aat ctg agc tcg gtg
ccc ttc 576 Leu Ser Ser Leu Ala Ile Thr Arg Cys Asn Leu Ser Ser Val
Pro Phe 180 185 190 caa gca ctg tac cac ctc agc ttc ctc agg gtc ctg
gat ctg tcc cag 624 Gln Ala Leu Tyr His Leu Ser Phe Leu Arg Val Leu
Asp Leu Ser Gln 195 200 205 aat ccc atc tca gcc atc cca gcc cga agg
ctc agc ccc ctg gtg cgg 672 Asn Pro Ile Ser Ala Ile Pro Ala Arg Arg
Leu Ser Pro Leu Val Arg 210 215 220 ctc cag gag cta cgc ctg tca ggg
gca tgc ctc acc tcc att gct gcc 720 Leu Gln Glu Leu Arg Leu Ser Gly
Ala Cys Leu Thr Ser Ile Ala Ala 225 230 235 cat gcc ttc cat ggc ttg
act gcc ttc cac ctc ctg gat gtg gca gat 768 His Ala Phe His Gly Leu
Thr Ala Phe His Leu Leu Asp Val Ala Asp 240 245 250 255 aac gcc ctt
cag aca cta gag gaa aca gct ttc cct tct cca gac aaa 816 Asn Ala Leu
Gln Thr Leu Glu Glu Thr Ala Phe Pro Ser Pro Asp Lys 260 265 270 ctg
gtc acc ttg agg ctg tct ggc aac ccc cta acc tgt gac tgc cgc 864 Leu
Val Thr Leu Arg Leu Ser Gly Asn Pro Leu Thr Cys Asp Cys Arg 275 280
285 ctc ctc tgg ctg ctc cgg ctc cgc cgc cac ctg gac ttt ggc atg tcc
912 Leu Leu Trp Leu Leu Arg Leu Arg Arg His Leu Asp Phe Gly Met Ser
290 295 300 ccc cct gcc tgt gct ggc ccc cat cat gtc cag ggg aag agc
ctg aag 960 Pro Pro Ala Cys Ala Gly Pro His His Val Gln Gly Lys Ser
Leu Lys 305 310 315 gag ttt tca gac atc ctg cct cca ggg cac ttc acc
tgc aaa cca gcc 1008 Glu Phe Ser Asp Ile Leu Pro Pro Gly His Phe
Thr Cys Lys Pro Ala 320 325 330 335 ctg atc cga aag tcg ggg cct cga
tgg gtc att gca gag gag ggc ggg 1056 Leu Ile Arg Lys Ser Gly Pro
Arg Trp Val Ile Ala Glu Glu Gly Gly 340 345 350 cat gcg gtt ttc tcc
tgc tct gga gat gga gac cca gcc ccc act gtc 1104 His Ala Val Phe
Ser Cys Ser Gly Asp Gly Asp Pro Ala Pro Thr Val 355 360 365 tcc tgg
atg agg cct cat ggg gct tgg ctg ggc agg gct ggg aga gta 1152 Ser
Trp Met Arg Pro His Gly Ala Trp Leu Gly Arg Ala Gly Arg Val 370 375
380 agg gtc cta gag gat ggg aca ctg gag atc cgc tca gtg cag cta cgg
1200 Arg Val Leu Glu Asp Gly Thr Leu Glu Ile Arg Ser Val Gln Leu
Arg 385 390 395 gac aga ggg gcc tat gtc tgt gtg gtt agc aat gtc gct
ggg aat gac 1248 Asp Arg Gly Ala Tyr Val Cys Val Val Ser Asn Val
Ala Gly Asn Asp 400 405 410 415 tcc ctg agg acc tgg ctg gaa gtc atc
cag gtg gaa cca cca aac ggc 1296 Ser Leu Arg Thr Trp Leu Glu Val
Ile Gln Val Glu Pro Pro Asn Gly 420 425 430 aca ctt tct gac ccc aac
atc acc gtg cca ggg atc cca ggg cct ttt 1344 Thr Leu Ser Asp Pro
Asn Ile Thr Val Pro Gly Ile Pro Gly Pro Phe 435 440 445 ttt ctg gat
agc aga ggt gtg gcc atg gtg ctg gca gtc ggc ttc ctc 1392 Phe Leu
Asp Ser Arg Gly Val Ala Met Val Leu Ala Val Gly Phe Leu 450 455 460
ccc ttc ctc acc tca gtg acc ctc tgc ttt ggc ctg att gcc ctt tgg
1440 Pro Phe Leu Thr Ser Val Thr Leu Cys Phe Gly Leu Ile Ala Leu
Trp 465 470 475 agc aag ggc aaa ggt cgg gtc aaa cat cac atg acc ttt
gac ttt gtg 1488 Ser Lys Gly Lys Gly Arg Val Lys His His Met Thr
Phe Asp Phe Val 480 485 490 495 gca cct cgg ccc tct ggg gat aaa aac
tct ggg ggt aac cgg gtc act 1536 Ala Pro Arg Pro Ser Gly Asp Lys
Asn Ser Gly Gly Asn Arg Val Thr 500 505 510 gcc aag ctc ttc
tgacctttcc ttcccca 1565 Ala Lys Leu Phe 515 92 515 PRT Homo sapiens
92 Met Leu Ser Arg Leu Ser Leu Leu Gln Glu Leu Asp Leu Ser Tyr Asn
1 5 10 15 Gln Leu Ser Thr Leu Glu Pro Gly Ala Phe His Gly Leu Gln
Ser Leu 20 25 30 Leu Thr Leu Arg Leu Gln Gly Asn Arg Leu Arg Ile
Met Gly Pro Gly 35 40 45 Val Phe Ser Gly Leu Ser Ala Leu Thr Leu
Leu Asp Leu Arg Leu Asn 50 55 60 Gln Ile Val Leu Phe Leu Asp Gly
Ala Phe Gly Glu Leu Gly Ser Leu 65 70 75 80 Gln Lys Leu Glu Val Gly
Asp Asn His Leu Val Phe Val Ala Pro Gly 85 90 95 Ala Phe Ala Gly
Leu Ala Lys Leu Ser Thr Leu Thr Leu Glu Arg Cys 100 105 110 Asn Leu
Ser Thr Val Pro Gly Leu Ala Leu Ala Arg Leu Pro Ala Leu 115 120 125
Val Ala Leu Arg Leu Arg Glu Leu Asp Ile Gly Arg Leu Pro Ala Gly 130
135 140 Ala Leu Arg Gly Leu Gly Gln Leu Lys Glu Leu Glu Ile His Leu
Trp 145 150 155 160 Pro Ser Leu Glu Ala Leu Asp Pro Gly Ser Leu Val
Gly Leu Asn Leu 165 170 175 Ser Ser Leu Ala Ile Thr Arg Cys Asn Leu
Ser Ser Val Pro Phe Gln 180 185 190 Ala Leu Tyr His Leu Ser Phe Leu
Arg Val Leu Asp Leu Ser Gln Asn 195 200 205 Pro Ile Ser Ala Ile Pro
Ala Arg Arg Leu Ser Pro Leu Val Arg Leu 210 215 220 Gln Glu Leu Arg
Leu Ser Gly Ala Cys Leu Thr Ser Ile Ala Ala His 225 230 235 240 Ala
Phe His Gly Leu Thr Ala Phe His Leu Leu Asp Val Ala Asp Asn 245 250
255 Ala Leu Gln Thr Leu Glu Glu Thr Ala Phe Pro Ser Pro Asp Lys Leu
260 265 270 Val Thr Leu Arg Leu Ser Gly Asn Pro Leu Thr Cys Asp Cys
Arg Leu 275 280 285 Leu Trp Leu Leu Arg Leu Arg Arg His Leu Asp Phe
Gly Met Ser Pro 290 295 300 Pro Ala Cys Ala Gly Pro His His Val Gln
Gly Lys Ser Leu Lys Glu 305 310 315 320 Phe Ser Asp Ile Leu Pro Pro
Gly His Phe Thr Cys Lys Pro Ala Leu 325 330 335 Ile Arg Lys Ser Gly
Pro Arg Trp Val Ile Ala Glu Glu Gly Gly His 340 345 350 Ala Val Phe
Ser Cys Ser Gly Asp Gly Asp Pro Ala Pro Thr Val Ser 355 360 365 Trp
Met Arg Pro His Gly Ala Trp Leu Gly Arg Ala Gly Arg Val Arg 370 375
380 Val Leu Glu Asp Gly Thr Leu Glu Ile Arg Ser Val Gln Leu Arg Asp
385 390 395 400 Arg Gly Ala Tyr Val Cys Val Val Ser Asn Val Ala Gly
Asn Asp Ser 405 410 415 Leu Arg Thr Trp Leu Glu Val Ile Gln Val Glu
Pro Pro Asn Gly Thr 420 425 430 Leu Ser Asp Pro Asn Ile Thr Val Pro
Gly Ile Pro Gly Pro Phe Phe 435 440 445 Leu Asp Ser Arg Gly Val Ala
Met Val Leu Ala Val Gly Phe Leu Pro 450 455 460 Phe Leu Thr Ser Val
Thr Leu Cys Phe Gly Leu Ile Ala Leu Trp Ser 465 470 475 480 Lys Gly
Lys Gly Arg Val Lys His His Met Thr Phe Asp Phe Val Ala 485 490 495
Pro Arg Pro Ser Gly Asp Lys Asn Ser Gly Gly Asn Arg Val Thr Ala 500
505 510 Lys Leu Phe 515 93 1780 DNA Homo sapiens CDS (26)..(1772)
93 ccaaccctct gcccggccgg tgccc atg ctt ctg tgg ctg ctg ctg ctg atc
52 Met Leu Leu Trp Leu Leu Leu Leu Ile 1 5 ctg act cct gga aga gaa
caa tca ggg gtg gcc cca aaa gct gta ctt 100 Leu Thr Pro Gly Arg Glu
Gln Ser Gly Val Ala Pro Lys Ala Val Leu 10 15 20 25 ctc ctc aat cct
cca tgg tcc aca gcc ttc aaa gga gaa aaa gtg gct 148 Leu Leu Asn Pro
Pro Trp Ser Thr Ala Phe Lys Gly Glu Lys Val Ala 30 35 40 ctc ata
tgc agc agc ata tca cat tcc cta gcc cag gga gac aca tat 196 Leu Ile
Cys Ser Ser Ile Ser His Ser Leu Ala Gln Gly Asp Thr Tyr 45 50 55
tgg tat cac gat gag aag ttg ttg aaa ata aaa cat gac aag atc caa 244
Trp Tyr His Asp Glu Lys Leu Leu Lys Ile Lys His Asp Lys Ile Gln 60
65 70 att aca gag cct gga aat tac caa tgt aag acc cga gga tcc tcc
ctc 292 Ile Thr Glu Pro Gly Asn Tyr Gln Cys Lys Thr Arg Gly Ser Ser
Leu 75 80 85 agt gat gcc gtg cat gtg gaa ttt tca cct gac tgg ctg
atc ctg cag 340 Ser Asp Ala Val His Val Glu Phe Ser Pro Asp Trp Leu
Ile Leu Gln 90 95 100 105 gct tta cat cct gtc ttt gaa gga gac aat
gtc att ctg aga tgt cag 388 Ala Leu His Pro Val Phe Glu Gly Asp Asn
Val Ile Leu Arg Cys Gln 110 115 120 ggg aaa gac aac aaa aac act cat
caa aag gtt tac tac aag gat gga 436 Gly Lys Asp Asn Lys Asn Thr His
Gln Lys Val Tyr Tyr Lys Asp Gly 125 130 135 aaa cag ctt cct aat agt
tat aat tta gag aag atc aca gtg aat tca 484 Lys Gln Leu Pro Asn Ser
Tyr Asn Leu Glu Lys Ile Thr Val Asn Ser 140 145 150 gtc tcc agg gat
aat agc aaa tat cat tgt act gct tat agg aag ttt 532 Val Ser Arg Asp
Asn Ser Lys Tyr His Cys Thr Ala Tyr Arg Lys Phe 155 160 165 tac ata
ctt gac att gaa gta act tca aaa ccc cta aat atc caa gtt 580 Tyr Ile
Leu Asp Ile Glu Val Thr Ser Lys Pro Leu Asn Ile Gln Val 170 175 180
185 caa gag ctg ttt cta cat cct gtg ctg aga gcc agc tct tcc acg ccc
628 Gln Glu Leu Phe Leu His Pro Val Leu Arg Ala Ser Ser Ser Thr Pro
190 195 200 ata gag ggg agt ccc atg acc ctg acc tgt gag acc cag ctc
tct cca 676 Ile Glu Gly Ser Pro Met Thr Leu Thr Cys Glu Thr Gln Leu
Ser Pro 205 210 215 cag agg cca gat gtc cag ctg caa ttc tcc ctc ttc
aga gat agc cag 724 Gln Arg Pro Asp Val Gln Leu Gln Phe Ser Leu Phe
Arg Asp Ser Gln 220 225 230 acc ctc gga ttg ggc tgg agc agg tcc ccc
aga ctc cag atc cct gcc 772 Thr Leu Gly Leu Gly Trp Ser Arg Ser Pro
Arg Leu Gln Ile Pro Ala 235 240 245 atg tgg act gaa gac tca ggg tct
tac tgg tgt gag gtg gag aca gtg 820 Met Trp Thr Glu Asp Ser Gly Ser
Tyr Trp Cys Glu Val Glu Thr Val 250 255 260 265 act cac agc atc aaa
aaa agg agc ctg aga tct cag ata cgt gta cag 868 Thr His Ser Ile Lys
Lys Arg Ser Leu Arg Ser Gln Ile Arg Val Gln 270 275 280 aga gtc cct
gtg tct aat gtg aat cta gag atc cgg ccc acc gga ggg 916 Arg Val Pro
Val Ser Asn Val Asn Leu Glu Ile Arg Pro Thr Gly Gly 285 290 295 cag
ctg att gaa gga gaa aat atg gtc ctt att tgc tca gta gcc cag 964 Gln
Leu Ile Glu Gly Glu Asn Met Val Leu Ile Cys Ser Val Ala Gln 300 305
310 ggt tca ggg act gtc aca ttc tcc tgg cac aaa gaa gga aga gta aga
1012 Gly Ser Gly Thr Val Thr Phe Ser Trp His Lys Glu Gly Arg Val
Arg 315 320 325 agc ctg ggt aga aag acc cag cgt tcc ctg ttg gca gag
ctg cat gtt 1060 Ser Leu Gly Arg Lys Thr Gln Arg Ser Leu Leu Ala
Glu Leu His Val 330 335 340 345 ctc acc gtg aag gag agt gat gca ggg
aga tac tac tgt gca gct gat 1108 Leu Thr Val Lys Glu Ser Asp Ala
Gly Arg Tyr Tyr Cys Ala Ala Asp 350 355 360 aac gtt cac agc ccc atc
ctc agc acg tgg att cga gtc acc gtg aga 1156 Asn Val His Ser Pro
Ile Leu Ser Thr Trp Ile Arg Val Thr Val Arg 365 370 375 att ccg gta
tct cac cct gtc ctc acc ttc agg gct ccc agg gcc cac 1204 Ile Pro
Val Ser His Pro Val Leu Thr Phe Arg Ala Pro Arg Ala His 380 385 390
act gtg gtg ggg gac ctg ctg gag ctt cac tgt gag tcc ctg aga ggc
1252 Thr Val Val Gly Asp Leu Leu Glu Leu His Cys Glu Ser Leu Arg
Gly 395 400 405 tct ccc ccg atc ctg tac cga ttt tat cat gag gat gtc
acc ctg ggg 1300 Ser Pro Pro Ile Leu Tyr Arg Phe Tyr His Glu Asp
Val Thr Leu Gly 410 415 420 425 aac agc tca gcc ccc tct gga gga gga
gcc tcc ttc aac ctc tct ctg 1348 Asn Ser Ser Ala Pro Ser Gly Gly
Gly Ala Ser Phe Asn Leu Ser Leu 430 435 440 act gca gaa cat tct gga
aac tac tcc tgt gat gca gac aat ggc ctg 1396 Thr Ala Glu His Ser
Gly Asn Tyr Ser Cys Asp Ala Asp Asn Gly Leu 445 450 455 ggg gcc cag
cac agt cat gga gtg agt ctc agg gtc aca gtt ccg gtg 1444 Gly Ala
Gln His Ser His Gly Val Ser Leu Arg Val Thr Val Pro Val 460 465 470
tct cgc ccc gtc ctc acc ctc agg gct ccc ggg gcc cag gct gtg gtg
1492 Ser Arg Pro Val Leu Thr Leu Arg Ala Pro Gly Ala Gln Ala Val
Val 475 480 485 ggg gac ctg ctg gag ctt cac tgt gag tcc ctg aga ggc
tcc ttc ccg 1540 Gly Asp Leu Leu Glu Leu His Cys Glu Ser Leu Arg
Gly Ser Phe Pro 490 495 500 505 atc ctg tac tgg ttt tat cac gag gat
gac acc ttg ggg aac atc tcg 1588 Ile Leu Tyr Trp Phe Tyr His Glu
Asp Asp Thr Leu Gly Asn Ile Ser 510 515 520 gcc cac tct gga gga ggg
gca tcc ttc aac ctc tct ctg act aca gaa 1636 Ala His Ser Gly Gly
Gly Ala Ser Phe Asn Leu Ser Leu Thr Thr Glu 525 530 535 cat tct gga
aac tac tca tgt gag gct gac aat ggc ctg ggg gcc cag 1684 His Ser
Gly Asn Tyr Ser Cys Glu Ala Asp Asn Gly Leu Gly Ala Gln 540 545 550
cac agt aaa gtg gtg aca ctc aat gtt aca ggt gtg tta ata gta cct
1732 His Ser Lys Val Val Thr Leu Asn Val Thr Gly Val
Leu Ile Val Pro 555 560 565 ggg cta gag gtc aca gtt atg gta aat aaa
ata gtt atc tgacagatt 1780 Gly Leu Glu Val Thr Val Met Val Asn Lys
Ile Val Ile 570 575 580 94 582 PRT Homo sapiens 94 Met Leu Leu Trp
Leu Leu Leu Leu Ile Leu Thr Pro Gly Arg Glu Gln 1 5 10 15 Ser Gly
Val Ala Pro Lys Ala Val Leu Leu Leu Asn Pro Pro Trp Ser 20 25 30
Thr Ala Phe Lys Gly Glu Lys Val Ala Leu Ile Cys Ser Ser Ile Ser 35
40 45 His Ser Leu Ala Gln Gly Asp Thr Tyr Trp Tyr His Asp Glu Lys
Leu 50 55 60 Leu Lys Ile Lys His Asp Lys Ile Gln Ile Thr Glu Pro
Gly Asn Tyr 65 70 75 80 Gln Cys Lys Thr Arg Gly Ser Ser Leu Ser Asp
Ala Val His Val Glu 85 90 95 Phe Ser Pro Asp Trp Leu Ile Leu Gln
Ala Leu His Pro Val Phe Glu 100 105 110 Gly Asp Asn Val Ile Leu Arg
Cys Gln Gly Lys Asp Asn Lys Asn Thr 115 120 125 His Gln Lys Val Tyr
Tyr Lys Asp Gly Lys Gln Leu Pro Asn Ser Tyr 130 135 140 Asn Leu Glu
Lys Ile Thr Val Asn Ser Val Ser Arg Asp Asn Ser Lys 145 150 155 160
Tyr His Cys Thr Ala Tyr Arg Lys Phe Tyr Ile Leu Asp Ile Glu Val 165
170 175 Thr Ser Lys Pro Leu Asn Ile Gln Val Gln Glu Leu Phe Leu His
Pro 180 185 190 Val Leu Arg Ala Ser Ser Ser Thr Pro Ile Glu Gly Ser
Pro Met Thr 195 200 205 Leu Thr Cys Glu Thr Gln Leu Ser Pro Gln Arg
Pro Asp Val Gln Leu 210 215 220 Gln Phe Ser Leu Phe Arg Asp Ser Gln
Thr Leu Gly Leu Gly Trp Ser 225 230 235 240 Arg Ser Pro Arg Leu Gln
Ile Pro Ala Met Trp Thr Glu Asp Ser Gly 245 250 255 Ser Tyr Trp Cys
Glu Val Glu Thr Val Thr His Ser Ile Lys Lys Arg 260 265 270 Ser Leu
Arg Ser Gln Ile Arg Val Gln Arg Val Pro Val Ser Asn Val 275 280 285
Asn Leu Glu Ile Arg Pro Thr Gly Gly Gln Leu Ile Glu Gly Glu Asn 290
295 300 Met Val Leu Ile Cys Ser Val Ala Gln Gly Ser Gly Thr Val Thr
Phe 305 310 315 320 Ser Trp His Lys Glu Gly Arg Val Arg Ser Leu Gly
Arg Lys Thr Gln 325 330 335 Arg Ser Leu Leu Ala Glu Leu His Val Leu
Thr Val Lys Glu Ser Asp 340 345 350 Ala Gly Arg Tyr Tyr Cys Ala Ala
Asp Asn Val His Ser Pro Ile Leu 355 360 365 Ser Thr Trp Ile Arg Val
Thr Val Arg Ile Pro Val Ser His Pro Val 370 375 380 Leu Thr Phe Arg
Ala Pro Arg Ala His Thr Val Val Gly Asp Leu Leu 385 390 395 400 Glu
Leu His Cys Glu Ser Leu Arg Gly Ser Pro Pro Ile Leu Tyr Arg 405 410
415 Phe Tyr His Glu Asp Val Thr Leu Gly Asn Ser Ser Ala Pro Ser Gly
420 425 430 Gly Gly Ala Ser Phe Asn Leu Ser Leu Thr Ala Glu His Ser
Gly Asn 435 440 445 Tyr Ser Cys Asp Ala Asp Asn Gly Leu Gly Ala Gln
His Ser His Gly 450 455 460 Val Ser Leu Arg Val Thr Val Pro Val Ser
Arg Pro Val Leu Thr Leu 465 470 475 480 Arg Ala Pro Gly Ala Gln Ala
Val Val Gly Asp Leu Leu Glu Leu His 485 490 495 Cys Glu Ser Leu Arg
Gly Ser Phe Pro Ile Leu Tyr Trp Phe Tyr His 500 505 510 Glu Asp Asp
Thr Leu Gly Asn Ile Ser Ala His Ser Gly Gly Gly Ala 515 520 525 Ser
Phe Asn Leu Ser Leu Thr Thr Glu His Ser Gly Asn Tyr Ser Cys 530 535
540 Glu Ala Asp Asn Gly Leu Gly Ala Gln His Ser Lys Val Val Thr Leu
545 550 555 560 Asn Val Thr Gly Val Leu Ile Val Pro Gly Leu Glu Val
Thr Val Met 565 570 575 Val Asn Lys Ile Val Ile 580 95 1263 DNA
Homo sapiens CDS (1)..(1263) 95 aag ctt gga gaa aaa gtg gct ctc ata
tgc agc agc ata tca cat tcc 48 Lys Leu Gly Glu Lys Val Ala Leu Ile
Cys Ser Ser Ile Ser His Ser 1 5 10 15 cta gcc cag gga gac aca tat
tgg tat cac gat gag aag ttg ttg aaa 96 Leu Ala Gln Gly Asp Thr Tyr
Trp Tyr His Asp Glu Lys Leu Leu Lys 20 25 30 ata aaa cat gac aag
atc caa att aca gag cct gga aat tac caa tgt 144 Ile Lys His Asp Lys
Ile Gln Ile Thr Glu Pro Gly Asn Tyr Gln Cys 35 40 45 aag acc cga
gga tcc tcc ctc agt gat gcc gtg cat gtg gaa ttt tca 192 Lys Thr Arg
Gly Ser Ser Leu Ser Asp Ala Val His Val Glu Phe Ser 50 55 60 cct
gac tgg ctg atc ctg cag gct tta cat cct gtc ttt gaa gga gac 240 Pro
Asp Trp Leu Ile Leu Gln Ala Leu His Pro Val Phe Glu Gly Asp 65 70
75 80 aat gtc att ctg aga tgt cag ggg aaa gac aac aaa aac act cat
caa 288 Asn Val Ile Leu Arg Cys Gln Gly Lys Asp Asn Lys Asn Thr His
Gln 85 90 95 aag gtt tac tac aag gat gga aaa cag ctt cct aat agt
tat aat tta 336 Lys Val Tyr Tyr Lys Asp Gly Lys Gln Leu Pro Asn Ser
Tyr Asn Leu 100 105 110 gag aag atc aca gtg aat tca gtc tcc agg gat
aat agc aaa tat cat 384 Glu Lys Ile Thr Val Asn Ser Val Ser Arg Asp
Asn Ser Lys Tyr His 115 120 125 tgt act gct tat agg aag ttt tac ata
ctt gac att gaa gta act tca 432 Cys Thr Ala Tyr Arg Lys Phe Tyr Ile
Leu Asp Ile Glu Val Thr Ser 130 135 140 aaa ccc cta aat atc caa gtt
caa gag ctg ttt cta cat cct gtg ctg 480 Lys Pro Leu Asn Ile Gln Val
Gln Glu Leu Phe Leu His Pro Val Leu 145 150 155 160 aga gcc agc tct
tcc acg ccc ata gag ggg agt ccc atg acc ctg acc 528 Arg Ala Ser Ser
Ser Thr Pro Ile Glu Gly Ser Pro Met Thr Leu Thr 165 170 175 tgt gag
acc cag ctc tct cca cag agg cca gat gtc cag ctg caa ttc 576 Cys Glu
Thr Gln Leu Ser Pro Gln Arg Pro Asp Val Gln Leu Gln Phe 180 185 190
tcc ctc ttc aga gat agc cag acc ctc gga ttg ggc tgg agt agg tcc 624
Ser Leu Phe Arg Asp Ser Gln Thr Leu Gly Leu Gly Trp Ser Arg Ser 195
200 205 ccc aga ctc cag atc cct gcc atg tgg act gaa gac tca ggg tct
tac 672 Pro Arg Leu Gln Ile Pro Ala Met Trp Thr Glu Asp Ser Gly Ser
Tyr 210 215 220 tgg tgt gag gtg gag aca gtg act cac agc atc aaa aaa
agg agc ctg 720 Trp Cys Glu Val Glu Thr Val Thr His Ser Ile Lys Lys
Arg Ser Leu 225 230 235 240 aga tct cag ata cgt gta cag aga gtc cct
gtg tct aat gtg aat cta 768 Arg Ser Gln Ile Arg Val Gln Arg Val Pro
Val Ser Asn Val Asn Leu 245 250 255 gag atc cgg ccc acc gga ggg cag
ctg att gaa gga gaa aat atg gtc 816 Glu Ile Arg Pro Thr Gly Gly Gln
Leu Ile Glu Gly Glu Asn Met Val 260 265 270 ctt att tgc tca gta gcc
cag ggt tca ggg act gtc aca ttc tcc tgg 864 Leu Ile Cys Ser Val Ala
Gln Gly Ser Gly Thr Val Thr Phe Ser Trp 275 280 285 cac aaa gaa gga
aga gta aga agc ctg ggt aga aag acc cag cgt tcc 912 His Lys Glu Gly
Arg Val Arg Ser Leu Gly Arg Lys Thr Gln Arg Ser 290 295 300 ctg ttg
gca gag ctg cat gtt ctc acc gtg aag gag agt gat gca ggg 960 Leu Leu
Ala Glu Leu His Val Leu Thr Val Lys Glu Ser Asp Ala Gly 305 310 315
320 aga tac tac tgt gca gct gat aac gtt cac agc ccc atc ctc agc acg
1008 Arg Tyr Tyr Cys Ala Ala Asp Asn Val His Ser Pro Ile Leu Ser
Thr 325 330 335 tgg att cga gtc acc gtg aga att ccg gta tct cac cct
gtc ctc acc 1056 Trp Ile Arg Val Thr Val Arg Ile Pro Val Ser His
Pro Val Leu Thr 340 345 350 ttc agg gct ccc agg gcc cac act gtg gtg
ggg gac ctg ctg gag ctt 1104 Phe Arg Ala Pro Arg Ala His Thr Val
Val Gly Asp Leu Leu Glu Leu 355 360 365 cac tgt gag tcc ctg aga ggc
tct ccc ccg atc ctg tac cga ttt tat 1152 His Cys Glu Ser Leu Arg
Gly Ser Pro Pro Ile Leu Tyr Arg Phe Tyr 370 375 380 cat gag gat gtc
acc ctg ggg aac agc tca gcc ccc tct gga gga gga 1200 His Glu Asp
Val Thr Leu Gly Asn Ser Ser Ala Pro Ser Gly Gly Gly 385 390 395 400
gcc tcc ttc aac ctc tct ctg act gca gaa cat tct gga aac tac tca
1248 Ala Ser Phe Asn Leu Ser Leu Thr Ala Glu His Ser Gly Asn Tyr
Ser 405 410 415 tgt gag gct ctc gag 1263 Cys Glu Ala Leu Glu 420 96
421 PRT Homo sapiens 96 Lys Leu Gly Glu Lys Val Ala Leu Ile Cys Ser
Ser Ile Ser His Ser 1 5 10 15 Leu Ala Gln Gly Asp Thr Tyr Trp Tyr
His Asp Glu Lys Leu Leu Lys 20 25 30 Ile Lys His Asp Lys Ile Gln
Ile Thr Glu Pro Gly Asn Tyr Gln Cys 35 40 45 Lys Thr Arg Gly Ser
Ser Leu Ser Asp Ala Val His Val Glu Phe Ser 50 55 60 Pro Asp Trp
Leu Ile Leu Gln Ala Leu His Pro Val Phe Glu Gly Asp 65 70 75 80 Asn
Val Ile Leu Arg Cys Gln Gly Lys Asp Asn Lys Asn Thr His Gln 85 90
95 Lys Val Tyr Tyr Lys Asp Gly Lys Gln Leu Pro Asn Ser Tyr Asn Leu
100 105 110 Glu Lys Ile Thr Val Asn Ser Val Ser Arg Asp Asn Ser Lys
Tyr His 115 120 125 Cys Thr Ala Tyr Arg Lys Phe Tyr Ile Leu Asp Ile
Glu Val Thr Ser 130 135 140 Lys Pro Leu Asn Ile Gln Val Gln Glu Leu
Phe Leu His Pro Val Leu 145 150 155 160 Arg Ala Ser Ser Ser Thr Pro
Ile Glu Gly Ser Pro Met Thr Leu Thr 165 170 175 Cys Glu Thr Gln Leu
Ser Pro Gln Arg Pro Asp Val Gln Leu Gln Phe 180 185 190 Ser Leu Phe
Arg Asp Ser Gln Thr Leu Gly Leu Gly Trp Ser Arg Ser 195 200 205 Pro
Arg Leu Gln Ile Pro Ala Met Trp Thr Glu Asp Ser Gly Ser Tyr 210 215
220 Trp Cys Glu Val Glu Thr Val Thr His Ser Ile Lys Lys Arg Ser Leu
225 230 235 240 Arg Ser Gln Ile Arg Val Gln Arg Val Pro Val Ser Asn
Val Asn Leu 245 250 255 Glu Ile Arg Pro Thr Gly Gly Gln Leu Ile Glu
Gly Glu Asn Met Val 260 265 270 Leu Ile Cys Ser Val Ala Gln Gly Ser
Gly Thr Val Thr Phe Ser Trp 275 280 285 His Lys Glu Gly Arg Val Arg
Ser Leu Gly Arg Lys Thr Gln Arg Ser 290 295 300 Leu Leu Ala Glu Leu
His Val Leu Thr Val Lys Glu Ser Asp Ala Gly 305 310 315 320 Arg Tyr
Tyr Cys Ala Ala Asp Asn Val His Ser Pro Ile Leu Ser Thr 325 330 335
Trp Ile Arg Val Thr Val Arg Ile Pro Val Ser His Pro Val Leu Thr 340
345 350 Phe Arg Ala Pro Arg Ala His Thr Val Val Gly Asp Leu Leu Glu
Leu 355 360 365 His Cys Glu Ser Leu Arg Gly Ser Pro Pro Ile Leu Tyr
Arg Phe Tyr 370 375 380 His Glu Asp Val Thr Leu Gly Asn Ser Ser Ala
Pro Ser Gly Gly Gly 385 390 395 400 Ala Ser Phe Asn Leu Ser Leu Thr
Ala Glu His Ser Gly Asn Tyr Ser 405 410 415 Cys Glu Ala Leu Glu 420
97 1263 DNA Homo sapiens CDS (1)..(1263) 97 aag ctt gga gaa aaa gtg
gct ctc ata tgc agc agc ata tca cat tcc 48 Lys Leu Gly Glu Lys Val
Ala Leu Ile Cys Ser Ser Ile Ser His Ser 1 5 10 15 cta gcc cag gga
gac aca tat tgg tat cac gat gag aag ttg ttg aaa 96 Leu Ala Gln Gly
Asp Thr Tyr Trp Tyr His Asp Glu Lys Leu Leu Lys 20 25 30 ata aaa
cat gac aag atc caa att aca gag cct gga aat tac caa tgt 144 Ile Lys
His Asp Lys Ile Gln Ile Thr Glu Pro Gly Asn Tyr Gln Cys 35 40 45
aag acc cga gga tcc tcc ctc agt gat gcc gtg cat gtg gaa ttt tca 192
Lys Thr Arg Gly Ser Ser Leu Ser Asp Ala Val His Val Glu Phe Ser 50
55 60 cct gac tgg ctg atc ctg cag gct tta cat cct gtc ttt gaa gga
gac 240 Pro Asp Trp Leu Ile Leu Gln Ala Leu His Pro Val Phe Glu Gly
Asp 65 70 75 80 aat gtc att ctg aga tgt cag ggg aaa gac aac aaa aac
act cat caa 288 Asn Val Ile Leu Arg Cys Gln Gly Lys Asp Asn Lys Asn
Thr His Gln 85 90 95 aag gtt tac tac aag gat gga aaa cag ctt cct
aat agt tat aat tta 336 Lys Val Tyr Tyr Lys Asp Gly Lys Gln Leu Pro
Asn Ser Tyr Asn Leu 100 105 110 gag aag atc aca gtg aat tca gtc tcc
agg gat aat agc aaa tat cat 384 Glu Lys Ile Thr Val Asn Ser Val Ser
Arg Asp Asn Ser Lys Tyr His 115 120 125 tgt act gct tat agg aag ttt
tac ata ctt gac att gaa gta act tca 432 Cys Thr Ala Tyr Arg Lys Phe
Tyr Ile Leu Asp Ile Glu Val Thr Ser 130 135 140 aaa ccc cta aat atc
caa gtt caa gag ctg ttt cta cat cct gtg ctg 480 Lys Pro Leu Asn Ile
Gln Val Gln Glu Leu Phe Leu His Pro Val Leu 145 150 155 160 aga gcc
agc tct tcc acg ccc ata gag ggg agt ccc atg acc ctg acc 528 Arg Ala
Ser Ser Ser Thr Pro Ile Glu Gly Ser Pro Met Thr Leu Thr 165 170 175
tgt gag acc cag ctc tct cca cag agg cca gat gtc cag ctg caa ttc 576
Cys Glu Thr Gln Leu Ser Pro Gln Arg Pro Asp Val Gln Leu Gln Phe 180
185 190 tcc ctc ttc aga gat agc cag acc ctc gga ttg ggc tgg agc agg
tcc 624 Ser Leu Phe Arg Asp Ser Gln Thr Leu Gly Leu Gly Trp Ser Arg
Ser 195 200 205 ccc aga ctc cag atc cct gcc atg tgg act gaa gac tca
ggg tct tac 672 Pro Arg Leu Gln Ile Pro Ala Met Trp Thr Glu Asp Ser
Gly Ser Tyr 210 215 220 tgg tgt gag gtg gag aca gtg act cac agc atc
aaa aaa agg agc ctg 720 Trp Cys Glu Val Glu Thr Val Thr His Ser Ile
Lys Lys Arg Ser Leu 225 230 235 240 aga tct cag ata cgt gta cag aga
gtc cct gtg tct aat gtg aat cta 768 Arg Ser Gln Ile Arg Val Gln Arg
Val Pro Val Ser Asn Val Asn Leu 245 250 255 gag atc cgg ccc acc gga
ggg cag ctg att gaa gga gaa aat atg gtc 816 Glu Ile Arg Pro Thr Gly
Gly Gln Leu Ile Glu Gly Glu Asn Met Val 260 265 270 ctt att tgc tca
gta gcc cag ggt tca ggg act gtc aca ttc tcc tgg 864 Leu Ile Cys Ser
Val Ala Gln Gly Ser Gly Thr Val Thr Phe Ser Trp 275 280 285 cac aaa
gaa gga aga gta aga agc ctg ggt aga aag acc cag cgt tcc 912 His Lys
Glu Gly Arg Val Arg Ser Leu Gly Arg Lys Thr Gln Arg Ser 290 295 300
ctg ttg gca gag ctg cat gtt ctc acc gtg aag gag agt gat gca ggg 960
Leu Leu Ala Glu Leu His Val Leu Thr Val Lys Glu Ser Asp Ala Gly 305
310 315 320 aga tac tac tgt gca gct gat aac gtt cac agc ccc atc ctc
agc acg 1008 Arg Tyr Tyr Cys Ala Ala Asp Asn Val His Ser Pro Ile
Leu Ser Thr 325 330 335 tgg att cga gtc acc gtg aga att ccg gta tct
cac cct gtc ctc acc 1056 Trp Ile Arg Val Thr Val Arg Ile Pro Val
Ser His Pro Val Leu Thr 340 345 350 ttc agg gct ccc agg gcc cac act
gtg gtg ggg gac ctg ctg gag ctt 1104 Phe Arg Ala Pro Arg Ala His
Thr Val Val Gly Asp Leu Leu Glu Leu 355 360 365 cac tgt gag tcc ctg
aga ggc tct ccc ccg atc ctg tac cga ttt tat 1152 His Cys Glu Ser
Leu Arg Gly Ser Pro Pro Ile Leu Tyr Arg Phe Tyr 370 375 380 cat gag
gat gtc acc ctg ggg aac agc tca gcc ccc tct gga gga gga 1200 His
Glu Asp Val Thr Leu Gly Asn Ser Ser Ala Pro Ser Gly Gly Gly 385 390
395 400 gcc tcc ttc aac ctc tct ctg act gca gaa cat tct gga aac tac
tca 1248 Ala Ser Phe Asn Leu Ser Leu Thr Ala Glu His Ser Gly Asn
Tyr Ser 405 410 415 tgt gag gct ctc gag 1263 Cys Glu Ala Leu Glu
420 98 421 PRT Homo sapiens 98 Lys Leu Gly Glu Lys Val Ala Leu Ile
Cys Ser Ser Ile Ser His Ser 1 5 10 15 Leu Ala Gln Gly Asp Thr Tyr
Trp Tyr His Asp Glu Lys Leu Leu Lys
20 25 30 Ile Lys His Asp Lys Ile Gln Ile Thr Glu Pro Gly Asn Tyr
Gln Cys 35 40 45 Lys Thr Arg Gly Ser Ser Leu Ser Asp Ala Val His
Val Glu Phe Ser 50 55 60 Pro Asp Trp Leu Ile Leu Gln Ala Leu His
Pro Val Phe Glu Gly Asp 65 70 75 80 Asn Val Ile Leu Arg Cys Gln Gly
Lys Asp Asn Lys Asn Thr His Gln 85 90 95 Lys Val Tyr Tyr Lys Asp
Gly Lys Gln Leu Pro Asn Ser Tyr Asn Leu 100 105 110 Glu Lys Ile Thr
Val Asn Ser Val Ser Arg Asp Asn Ser Lys Tyr His 115 120 125 Cys Thr
Ala Tyr Arg Lys Phe Tyr Ile Leu Asp Ile Glu Val Thr Ser 130 135 140
Lys Pro Leu Asn Ile Gln Val Gln Glu Leu Phe Leu His Pro Val Leu 145
150 155 160 Arg Ala Ser Ser Ser Thr Pro Ile Glu Gly Ser Pro Met Thr
Leu Thr 165 170 175 Cys Glu Thr Gln Leu Ser Pro Gln Arg Pro Asp Val
Gln Leu Gln Phe 180 185 190 Ser Leu Phe Arg Asp Ser Gln Thr Leu Gly
Leu Gly Trp Ser Arg Ser 195 200 205 Pro Arg Leu Gln Ile Pro Ala Met
Trp Thr Glu Asp Ser Gly Ser Tyr 210 215 220 Trp Cys Glu Val Glu Thr
Val Thr His Ser Ile Lys Lys Arg Ser Leu 225 230 235 240 Arg Ser Gln
Ile Arg Val Gln Arg Val Pro Val Ser Asn Val Asn Leu 245 250 255 Glu
Ile Arg Pro Thr Gly Gly Gln Leu Ile Glu Gly Glu Asn Met Val 260 265
270 Leu Ile Cys Ser Val Ala Gln Gly Ser Gly Thr Val Thr Phe Ser Trp
275 280 285 His Lys Glu Gly Arg Val Arg Ser Leu Gly Arg Lys Thr Gln
Arg Ser 290 295 300 Leu Leu Ala Glu Leu His Val Leu Thr Val Lys Glu
Ser Asp Ala Gly 305 310 315 320 Arg Tyr Tyr Cys Ala Ala Asp Asn Val
His Ser Pro Ile Leu Ser Thr 325 330 335 Trp Ile Arg Val Thr Val Arg
Ile Pro Val Ser His Pro Val Leu Thr 340 345 350 Phe Arg Ala Pro Arg
Ala His Thr Val Val Gly Asp Leu Leu Glu Leu 355 360 365 His Cys Glu
Ser Leu Arg Gly Ser Pro Pro Ile Leu Tyr Arg Phe Tyr 370 375 380 His
Glu Asp Val Thr Leu Gly Asn Ser Ser Ala Pro Ser Gly Gly Gly 385 390
395 400 Ala Ser Phe Asn Leu Ser Leu Thr Ala Glu His Ser Gly Asn Tyr
Ser 405 410 415 Cys Glu Ala Leu Glu 420 99 1263 DNA Homo sapiens
CDS (1)..(1263) 99 aag ctt gga gaa aaa gtg gct ctc ata tgc agc agc
ata tca cat tcc 48 Lys Leu Gly Glu Lys Val Ala Leu Ile Cys Ser Ser
Ile Ser His Ser 1 5 10 15 cta gcc cag gga gac aca tat tgg tat cac
gat gag aag ttg ttg aaa 96 Leu Ala Gln Gly Asp Thr Tyr Trp Tyr His
Asp Glu Lys Leu Leu Lys 20 25 30 ata aaa cat gac aag atc caa att
aca gag cct gga aat tac caa tgt 144 Ile Lys His Asp Lys Ile Gln Ile
Thr Glu Pro Gly Asn Tyr Gln Cys 35 40 45 aag acc cga gga tcc tcc
ctc agt gat gcc gtg cat gtg gaa ttt tca 192 Lys Thr Arg Gly Ser Ser
Leu Ser Asp Ala Val His Val Glu Phe Ser 50 55 60 cct gac tgg ctg
atc ctg cag gct tta cat cct gtc ttt gaa gga gac 240 Pro Asp Trp Leu
Ile Leu Gln Ala Leu His Pro Val Phe Glu Gly Asp 65 70 75 80 aat gtc
att ctg aga tgt cag ggg aaa gac aac aaa aac act cat caa 288 Asn Val
Ile Leu Arg Cys Gln Gly Lys Asp Asn Lys Asn Thr His Gln 85 90 95
aag gtt tac tac aag gat gga aaa cag ctt cct aat agt tat aat tta 336
Lys Val Tyr Tyr Lys Asp Gly Lys Gln Leu Pro Asn Ser Tyr Asn Leu 100
105 110 gag aag atc aca gtg aat tca gtc tcc agg gat aat agc aaa tat
cat 384 Glu Lys Ile Thr Val Asn Ser Val Ser Arg Asp Asn Ser Lys Tyr
His 115 120 125 tgt act gct tat agg aag ttt tac ata ctt gac att gaa
gta act tca 432 Cys Thr Ala Tyr Arg Lys Phe Tyr Ile Leu Asp Ile Glu
Val Thr Ser 130 135 140 aaa ccc cta aat atc caa gtt cag gag ctg ttt
cta cat cct gtg ctg 480 Lys Pro Leu Asn Ile Gln Val Gln Glu Leu Phe
Leu His Pro Val Leu 145 150 155 160 aga gcc agc tct tcc acg ccc ata
gag ggg agt ccc atg acc ctg acc 528 Arg Ala Ser Ser Ser Thr Pro Ile
Glu Gly Ser Pro Met Thr Leu Thr 165 170 175 tgt gag acc cag ctc tct
cca cag agg cca gat gtc cag ctg caa ttc 576 Cys Glu Thr Gln Leu Ser
Pro Gln Arg Pro Asp Val Gln Leu Gln Phe 180 185 190 tcc ctc ttc aga
gat agc cag acc ccc gga ttg ggc tgg agc agg tcc 624 Ser Leu Phe Arg
Asp Ser Gln Thr Pro Gly Leu Gly Trp Ser Arg Ser 195 200 205 ccc aga
ctc cag atc cct gcc atg tgg act gaa gac tca ggg tct tac 672 Pro Arg
Leu Gln Ile Pro Ala Met Trp Thr Glu Asp Ser Gly Ser Tyr 210 215 220
tgg tgt gag gtg gag aca gtg act cac agc atc aaa aaa agg agc ctg 720
Trp Cys Glu Val Glu Thr Val Thr His Ser Ile Lys Lys Arg Ser Leu 225
230 235 240 aga tct cag ata cgt gta cag aga gtc cct gtg tct aat gtg
aat cta 768 Arg Ser Gln Ile Arg Val Gln Arg Val Pro Val Ser Asn Val
Asn Leu 245 250 255 gag atc cgg ccc acc gga ggg cag ctg att gaa gga
gaa aat atg gtc 816 Glu Ile Arg Pro Thr Gly Gly Gln Leu Ile Glu Gly
Glu Asn Met Val 260 265 270 ctt att tgc tca gta gcc cag ggt tca ggg
act gtc aca ttc tcc tgg 864 Leu Ile Cys Ser Val Ala Gln Gly Ser Gly
Thr Val Thr Phe Ser Trp 275 280 285 cac aaa gaa gga aga gta aga agc
ctg ggt aga aag acc cag cgt tcc 912 His Lys Glu Gly Arg Val Arg Ser
Leu Gly Arg Lys Thr Gln Arg Ser 290 295 300 ctg ttg gca gag ctg cat
gtt ctc acc gtg aag gag agt gat gca ggg 960 Leu Leu Ala Glu Leu His
Val Leu Thr Val Lys Glu Ser Asp Ala Gly 305 310 315 320 aga tac tac
tgt gca gct gat aac gtt cac agc ccc atc ctc agc acg 1008 Arg Tyr
Tyr Cys Ala Ala Asp Asn Val His Ser Pro Ile Leu Ser Thr 325 330 335
tgg att cga gtc acc gtg aga att ccg gta tct cac cct gtc ccc acc
1056 Trp Ile Arg Val Thr Val Arg Ile Pro Val Ser His Pro Val Pro
Thr 340 345 350 ttc agg gct ccc agg gcc cac act gtg gtg ggg gac ctg
ctg gag ctt 1104 Phe Arg Ala Pro Arg Ala His Thr Val Val Gly Asp
Leu Leu Glu Leu 355 360 365 cac tgt gag tcc ctg aga ggc tct ccc ccg
atc ctg tac cga ttt tat 1152 His Cys Glu Ser Leu Arg Gly Ser Pro
Pro Ile Leu Tyr Arg Phe Tyr 370 375 380 cat gag gat gtc acc ctg ggg
aac agc tca gcc ccc tct gga gga gga 1200 His Glu Asp Val Thr Leu
Gly Asn Ser Ser Ala Pro Ser Gly Gly Gly 385 390 395 400 gac tcc ttc
aac ctc tct ctg act gca gaa cat tct gga aac tac tca 1248 Asp Ser
Phe Asn Leu Ser Leu Thr Ala Glu His Ser Gly Asn Tyr Ser 405 410 415
tgt gag gct ctc gag 1263 Cys Glu Ala Leu Glu 420 100 421 PRT Homo
sapiens 100 Lys Leu Gly Glu Lys Val Ala Leu Ile Cys Ser Ser Ile Ser
His Ser 1 5 10 15 Leu Ala Gln Gly Asp Thr Tyr Trp Tyr His Asp Glu
Lys Leu Leu Lys 20 25 30 Ile Lys His Asp Lys Ile Gln Ile Thr Glu
Pro Gly Asn Tyr Gln Cys 35 40 45 Lys Thr Arg Gly Ser Ser Leu Ser
Asp Ala Val His Val Glu Phe Ser 50 55 60 Pro Asp Trp Leu Ile Leu
Gln Ala Leu His Pro Val Phe Glu Gly Asp 65 70 75 80 Asn Val Ile Leu
Arg Cys Gln Gly Lys Asp Asn Lys Asn Thr His Gln 85 90 95 Lys Val
Tyr Tyr Lys Asp Gly Lys Gln Leu Pro Asn Ser Tyr Asn Leu 100 105 110
Glu Lys Ile Thr Val Asn Ser Val Ser Arg Asp Asn Ser Lys Tyr His 115
120 125 Cys Thr Ala Tyr Arg Lys Phe Tyr Ile Leu Asp Ile Glu Val Thr
Ser 130 135 140 Lys Pro Leu Asn Ile Gln Val Gln Glu Leu Phe Leu His
Pro Val Leu 145 150 155 160 Arg Ala Ser Ser Ser Thr Pro Ile Glu Gly
Ser Pro Met Thr Leu Thr 165 170 175 Cys Glu Thr Gln Leu Ser Pro Gln
Arg Pro Asp Val Gln Leu Gln Phe 180 185 190 Ser Leu Phe Arg Asp Ser
Gln Thr Pro Gly Leu Gly Trp Ser Arg Ser 195 200 205 Pro Arg Leu Gln
Ile Pro Ala Met Trp Thr Glu Asp Ser Gly Ser Tyr 210 215 220 Trp Cys
Glu Val Glu Thr Val Thr His Ser Ile Lys Lys Arg Ser Leu 225 230 235
240 Arg Ser Gln Ile Arg Val Gln Arg Val Pro Val Ser Asn Val Asn Leu
245 250 255 Glu Ile Arg Pro Thr Gly Gly Gln Leu Ile Glu Gly Glu Asn
Met Val 260 265 270 Leu Ile Cys Ser Val Ala Gln Gly Ser Gly Thr Val
Thr Phe Ser Trp 275 280 285 His Lys Glu Gly Arg Val Arg Ser Leu Gly
Arg Lys Thr Gln Arg Ser 290 295 300 Leu Leu Ala Glu Leu His Val Leu
Thr Val Lys Glu Ser Asp Ala Gly 305 310 315 320 Arg Tyr Tyr Cys Ala
Ala Asp Asn Val His Ser Pro Ile Leu Ser Thr 325 330 335 Trp Ile Arg
Val Thr Val Arg Ile Pro Val Ser His Pro Val Pro Thr 340 345 350 Phe
Arg Ala Pro Arg Ala His Thr Val Val Gly Asp Leu Leu Glu Leu 355 360
365 His Cys Glu Ser Leu Arg Gly Ser Pro Pro Ile Leu Tyr Arg Phe Tyr
370 375 380 His Glu Asp Val Thr Leu Gly Asn Ser Ser Ala Pro Ser Gly
Gly Gly 385 390 395 400 Asp Ser Phe Asn Leu Ser Leu Thr Ala Glu His
Ser Gly Asn Tyr Ser 405 410 415 Cys Glu Ala Leu Glu 420 101 360 DNA
Homo sapiens CDS (3)..(279) 101 cg ctg ctc ctg ctg ctg ctg gcg ctg
tac acc gcg cgt gtg gac ggg 47 Leu Leu Leu Leu Leu Leu Ala Leu Tyr
Thr Ala Arg Val Asp Gly 1 5 10 15 tcc aaa tgc aag tgc tcc cgg aag
gga ccc aag atc cgc tac agc gac 95 Ser Lys Cys Lys Cys Ser Arg Lys
Gly Pro Lys Ile Arg Tyr Ser Asp 20 25 30 gtg aag aag ctg gaa atg
aag cca aag tac ccg cac tgc gag gag aag 143 Val Lys Lys Leu Glu Met
Lys Pro Lys Tyr Pro His Cys Glu Glu Lys 35 40 45 atg gtt atc atc
acc acc aag agc gtg tcc agg tac cga ggt cag gag 191 Met Val Ile Ile
Thr Thr Lys Ser Val Ser Arg Tyr Arg Gly Gln Glu 50 55 60 cac tgc
ctg cac ccc aag ctg cag agc acc aag cgc ttc atc aag tgg 239 His Cys
Leu His Pro Lys Leu Gln Ser Thr Lys Arg Phe Ile Lys Trp 65 70 75
tac aac gcc tgg aac gag aag cgc agg gtc tac gaa gaa tagggtgaaa 288
Tyr Asn Ala Trp Asn Glu Lys Arg Arg Val Tyr Glu Glu 80 85 90
aacctcagaa gggaaaactc caaaccagtt gggagacttg tgcaaaggac 338
tttgcagatt aaaaaaaaaa aa 360 102 92 PRT Homo sapiens 102 Leu Leu
Leu Leu Leu Leu Ala Leu Tyr Thr Ala Arg Val Asp Gly Ser 1 5 10 15
Lys Cys Lys Cys Ser Arg Lys Gly Pro Lys Ile Arg Tyr Ser Asp Val 20
25 30 Lys Lys Leu Glu Met Lys Pro Lys Tyr Pro His Cys Glu Glu Lys
Met 35 40 45 Val Ile Ile Thr Thr Lys Ser Val Ser Arg Tyr Arg Gly
Gln Glu His 50 55 60 Cys Leu His Pro Lys Leu Gln Ser Thr Lys Arg
Phe Ile Lys Trp Tyr 65 70 75 80 Asn Ala Trp Asn Glu Lys Arg Arg Val
Tyr Glu Glu 85 90 103 228 DNA Homo sapiens CDS (1)..(228) 103 aaa
tgc aag tgc tcc cgg aag gga ccc aag atc cgc tac agc gac gtg 48 Lys
Cys Lys Cys Ser Arg Lys Gly Pro Lys Ile Arg Tyr Ser Asp Val 1 5 10
15 aag aag ctg gaa atg aag cca aag tac ccg cac tgc gag gag aag atg
96 Lys Lys Leu Glu Met Lys Pro Lys Tyr Pro His Cys Glu Glu Lys Met
20 25 30 gtt atc atc acc acc aag agc gtg tcc agg tac cga ggt cag
gag cac 144 Val Ile Ile Thr Thr Lys Ser Val Ser Arg Tyr Arg Gly Gln
Glu His 35 40 45 tgc ctg cac ccc aag ctg cag agc acc aag cgc ttc
atc aag tgg tac 192 Cys Leu His Pro Lys Leu Gln Ser Thr Lys Arg Phe
Ile Lys Trp Tyr 50 55 60 aac gcc tgg aac gag aag cgc agg gtc tac
gaa gaa 228 Asn Ala Trp Asn Glu Lys Arg Arg Val Tyr Glu Glu 65 70
75 104 76 PRT Homo sapiens 104 Lys Cys Lys Cys Ser Arg Lys Gly Pro
Lys Ile Arg Tyr Ser Asp Val 1 5 10 15 Lys Lys Leu Glu Met Lys Pro
Lys Tyr Pro His Cys Glu Glu Lys Met 20 25 30 Val Ile Ile Thr Thr
Lys Ser Val Ser Arg Tyr Arg Gly Gln Glu His 35 40 45 Cys Leu His
Pro Lys Leu Gln Ser Thr Lys Arg Phe Ile Lys Trp Tyr 50 55 60 Asn
Ala Trp Asn Glu Lys Arg Arg Val Tyr Glu Glu 65 70 75 105 228 DNA
Homo sapiens CDS (1)..(228) 105 aaa tgc aag tgc tcc cgg aag gga ccc
aag atc cgc tac agc gac gtg 48 Lys Cys Lys Cys Ser Arg Lys Gly Pro
Lys Ile Arg Tyr Ser Asp Val 1 5 10 15 aag aag ctg gaa atg aag cca
aag tac ccg cac tgc gag gag aag atg 96 Lys Lys Leu Glu Met Lys Pro
Lys Tyr Pro His Cys Glu Glu Lys Met 20 25 30 gtt atc atc acc acc
aag agc gtg tcc agg tac cga ggt cag gag cac 144 Val Ile Ile Thr Thr
Lys Ser Val Ser Arg Tyr Arg Gly Gln Glu His 35 40 45 tgc ctg cac
ccc aag ctg cag agc acc aag cgc ttc atc aag tgg tac 192 Cys Leu His
Pro Lys Leu Gln Ser Thr Lys Arg Phe Ile Lys Trp Tyr 50 55 60 aac
gcc tgg aac gag aag cgc agg gtc tac gaa gaa 228 Asn Ala Trp Asn Glu
Lys Arg Arg Val Tyr Glu Glu 65 70 75 106 76 PRT Homo sapiens 106
Lys Cys Lys Cys Ser Arg Lys Gly Pro Lys Ile Arg Tyr Ser Asp Val 1 5
10 15 Lys Lys Leu Glu Met Lys Pro Lys Tyr Pro His Cys Glu Glu Lys
Met 20 25 30 Val Ile Ile Thr Thr Lys Ser Val Ser Arg Tyr Arg Gly
Gln Glu His 35 40 45 Cys Leu His Pro Lys Leu Gln Ser Thr Lys Arg
Phe Ile Lys Trp Tyr 50 55 60 Asn Ala Trp Asn Glu Lys Arg Arg Val
Tyr Glu Glu 65 70 75 107 619 DNA Homo sapiens CDS (1)..(604) 107
gct gcc tgc ctc ctc atg ttc ccc tcc acc aca gcg gac tgc ctg tcg 48
Ala Ala Cys Leu Leu Met Phe Pro Ser Thr Thr Ala Asp Cys Leu Ser 1 5
10 15 cgg tgc tcc ttg tgt gct gta aag acc cag gat ggt ccc aaa cct
atc 96 Arg Cys Ser Leu Cys Ala Val Lys Thr Gln Asp Gly Pro Lys Pro
Ile 20 25 30 aat ccc ctg att tgc tcc ctg caa tgc cag gct gcc ctg
ctg ccc tct 144 Asn Pro Leu Ile Cys Ser Leu Gln Cys Gln Ala Ala Leu
Leu Pro Ser 35 40 45 gag gaa tgg gag aga tgc cag agc ttt ctg tct
ttt ttc acc ccc tcc 192 Glu Glu Trp Glu Arg Cys Gln Ser Phe Leu Ser
Phe Phe Thr Pro Ser 50 55 60 acc ctt ggg ctc aat gac aag gag gac
ttg ggg agc aag tcg gtt ggg 240 Thr Leu Gly Leu Asn Asp Lys Glu Asp
Leu Gly Ser Lys Ser Val Gly 65 70 75 80 gaa ggg ccc tac agt gag ctg
gcc aag ctc tct ggg tca ttc ctg aag 288 Glu Gly Pro Tyr Ser Glu Leu
Ala Lys Leu Ser Gly Ser Phe Leu Lys 85 90 95 gag ctg aac gat ggt
gcc atg gag act ggc aca ctc tat ctc gct gag 336 Glu Leu Asn Asp Gly
Ala Met Glu Thr Gly Thr Leu Tyr Leu Ala Glu 100 105 110 gag gac ccc
aag gag cag gtc aaa cgc tat ggg ggc ttt ttg cgc aaa 384 Glu Asp Pro
Lys Glu Gln Val Lys Arg Tyr Gly Gly Phe Leu Arg Lys 115 120 125 tac
ccc aag agg agc tca gag gtg gct ggg gag ggg gac ggg gat agc 432 Tyr
Pro Lys Arg Ser Ser Glu Val Ala Gly Glu Gly Asp Gly Asp Ser 130 135
140 atg ggc cat gag gac ctg tac aaa cgc tat ggg ggc ttc ttg cgg cgc
480 Met Gly
His Glu Asp Leu Tyr Lys Arg Tyr Gly Gly Phe Leu Arg Arg 145 150 155
160 att cgt ccc aag ctc aag tgg gac aac cag aag cgc tat ggc ggt ttt
528 Ile Arg Pro Lys Leu Lys Trp Asp Asn Gln Lys Arg Tyr Gly Gly Phe
165 170 175 ctc cgg cgc cag ttc aag gtg gtg act cgg tct cag gaa gat
ccg aat 576 Leu Arg Arg Gln Phe Lys Val Val Thr Arg Ser Gln Glu Asp
Pro Asn 180 185 190 gct tac tct gga gag ctt ttt gat gca taagcacttc
ttttca 619 Ala Tyr Ser Gly Glu Leu Phe Asp Ala 195 200 108 201 PRT
Homo sapiens 108 Ala Ala Cys Leu Leu Met Phe Pro Ser Thr Thr Ala
Asp Cys Leu Ser 1 5 10 15 Arg Cys Ser Leu Cys Ala Val Lys Thr Gln
Asp Gly Pro Lys Pro Ile 20 25 30 Asn Pro Leu Ile Cys Ser Leu Gln
Cys Gln Ala Ala Leu Leu Pro Ser 35 40 45 Glu Glu Trp Glu Arg Cys
Gln Ser Phe Leu Ser Phe Phe Thr Pro Ser 50 55 60 Thr Leu Gly Leu
Asn Asp Lys Glu Asp Leu Gly Ser Lys Ser Val Gly 65 70 75 80 Glu Gly
Pro Tyr Ser Glu Leu Ala Lys Leu Ser Gly Ser Phe Leu Lys 85 90 95
Glu Leu Asn Asp Gly Ala Met Glu Thr Gly Thr Leu Tyr Leu Ala Glu 100
105 110 Glu Asp Pro Lys Glu Gln Val Lys Arg Tyr Gly Gly Phe Leu Arg
Lys 115 120 125 Tyr Pro Lys Arg Ser Ser Glu Val Ala Gly Glu Gly Asp
Gly Asp Ser 130 135 140 Met Gly His Glu Asp Leu Tyr Lys Arg Tyr Gly
Gly Phe Leu Arg Arg 145 150 155 160 Ile Arg Pro Lys Leu Lys Trp Asp
Asn Gln Lys Arg Tyr Gly Gly Phe 165 170 175 Leu Arg Arg Gln Phe Lys
Val Val Thr Arg Ser Gln Glu Asp Pro Asn 180 185 190 Ala Tyr Ser Gly
Glu Leu Phe Asp Ala 195 200 109 22 DNA Artificial Sequence
Description of Artificial Sequence Forward Primer 109 tcttccagaa
ggacatcaac tg 22 110 26 DNA Artificial Sequence Description of
Artificial Sequence probe 110 cagcttcatc cacttgagtt tccagg 26 111
22 DNA Artificial Sequence Description of Artificial Sequence
Reverse Primer 111 cccctcgtcc aggatatagt ac 22 112 30 DNA
Artificial Sequence Description of Artificial Sequence Forward
Primer 112 gtagtgaagc aggatagttc ataaatagaa 30 113 26 DNA
Artificial Sequence Description of Artificial Sequence probe 113
agtggaagcg ccttctcatc cttcat 26 114 18 DNA Artificial Sequence
Description of Artificial Sequence Reverse Primer 114 gcagtggtca
cgtttgga 18 115 18 DNA Artificial Sequence Description of
Artificial Sequence Forward Primer 115 gtgaggcggc agatcttc 18 116
25 DNA Artificial Sequence Description of Artificial Sequence probe
116 agctgaatca tctgcagcct gcatt 25 117 18 DNA Artificial Sequence
Description of Artificial Sequence Reverse Primer 117 attcccaggc
atgatgct 18 118 18 DNA Artificial Sequence Description of
Artificial Sequence Forward Primer 118 gtgaggcggc agatcttc 18 119
25 DNA Artificial Sequence Description of Artificial Sequence probe
119 agctgaatca tctgcagcct gcatt 25 120 18 DNA Artificial Sequence
Description of Artificial Sequence Reverse Primer 120 attcccaggc
atgatgct 18 121 18 DNA Artificial Sequence Description of
Artificial Sequence Forward Primer 121 gtgaggcggc agatcttc 18 122
25 DNA Artificial Sequence Description of Artificial Sequence probe
122 agctgaatca tctgcagcct gcatt 25 123 18 DNA Artificial Sequence
Description of Artificial Sequence Reverse Primer 123 attcccaggc
atgatgct 18 124 23 DNA Artificial Sequence Description of
Artificial Sequence Forward Primer 124 acaacgagac caaacaggtg act 23
125 22 DNA Artificial Sequence Description of Artificial Sequence
probe 125 tcaagctgcc caactgtgcc cc 22 126 20 DNA Artificial
Sequence Description of Artificial Sequence Reverse Primer 126
ggccacggga taggtgtaga 20 127 23 DNA Artificial Sequence Description
of Artificial Sequence Forward Primer 127 acaacgagac caaacaggtg act
23 128 22 DNA Artificial Sequence Description of Artificial
Sequence probe 128 caactgtgcc ccgggagtcg ac 22 129 20 DNA
Artificial Sequence Description of Artificial Sequence Reverse
Primer 129 ggccacggga taggtgtaga 20 130 21 DNA Artificial Sequence
Description of Artificial Sequence Forward Primer 130 actctcggag
gaggacattt t 21 131 23 DNA Artificial Sequence Description of
Artificial Sequence probe 131 cagtcccctg tgtccctctg ctg 23 132 22
DNA Artificial Sequence Description of Artificial Sequence Reverse
Primer 132 cactggagat agcagacaga ca 22 133 21 DNA Artificial
Sequence Description of Artificial Sequence Forward Primer 133
actctcggag gaggacattt t 21 134 23 DNA Artificial Sequence
Description of Artificial Sequence probe 134 cagtcccctg tgtccctctg
ctg 23 135 22 DNA Artificial Sequence Description of Artificial
Sequence Reverse Primer 135 cactggagat agcagacaga ca 22 136 19 DNA
Artificial Sequence Description of Artificial Sequence Forward
Primer 136 ccagccccaa gtcctggat 19 137 24 DNA Artificial Sequence
Description of Artificial Sequence probe 137 aaccttggtg tccactgggc
caca 24 138 20 DNA Artificial Sequence Description of Artificial
Sequence Reverse Primer 138 atcatggctg agccctgagt 20 139 20 DNA
Artificial Sequence Description of Artificial Sequence Forward
Primer 139 ggtcatggtc ctggagaagt 20 140 25 DNA Artificial Sequence
Description of Artificial Sequence probe 140 acctggcagc cctaccagtt
ctacg 25 141 19 DNA Artificial Sequence Description of Artificial
Sequence Reverse Primer 141 acataccgaa ggcctccat 19 142 19 DNA
Artificial Sequence Description of Artificial Sequence Forward
Primer 142 ggcagggatg aaactgtca 19 143 26 DNA Artificial Sequence
Description of Artificial Sequence probe 143 ccttggcccc aatgtagaga
acactg 26 144 22 DNA Artificial Sequence Description of Artificial
Sequence Reverse Primer 144 ctcccgtgac atacactttg ac 22 145 20 DNA
Artificial Sequence Description of Artificial Sequence Forward
Primer 145 catggagact cccctttgac 20 146 26 DNA Artificial Sequence
Description of Artificial Sequence probe 146 cctgaaggag gtcaccatct
cattga 26 147 21 DNA Artificial Sequence Description of Artificial
Sequence Reverse Primer 147 cggatcttgg acttcaatct c 21 148 21 DNA
Artificial Sequence Description of Artificial Sequence Forward
Primer 148 tgggacaaag aaagagacca a 21 149 24 DNA Artificial
Sequence Description of Artificial Sequence probe 149 ttgctgacgc
ctgtgatcct cact 24 150 19 DNA Artificial Sequence Description of
Artificial Sequence Reverse Primer 150 caagggctga gtggagaag 19 151
20 DNA Artificial Sequence Description of Artificial Sequence
Forward Primer 151 cttcatccgc ttctccaaat 20 152 26 DNA Artificial
Sequence Description of Artificial Sequence probe 152 cctgaaaacc
acatcgtctt ccctgt 26 153 21 DNA Artificial Sequence Description of
Artificial Sequence Reverse Primer 153 ctcatccaga ctggccatta c 21
154 20 DNA Artificial Sequence Description of Artificial Sequence
Forward Primer 154 ggagaacttc atccgcttct 20 155 26 DNA Artificial
Sequence Description of Artificial Sequence probe 155 cctgaaaacc
acatcgtctt ccctgt 26 156 21 DNA Artificial Sequence Description of
Artificial Sequence Reverse Primer 156 ctcatccaga ctggccatta c 21
157 22 DNA Artificial Sequence Description of Artificial Sequence
Forward Primer 157 cctttgacgt tgaaaggtac ag 22 158 26 DNA
Artificial Sequence Description of Artificial Sequence probe 158
tcaagttgga cagcacttta cctttg 26 159 22 DNA Artificial Sequence
Description of Artificial Sequence Reverse Primer 159 tctgcagaat
ccaaatctct gt 22 160 22 DNA Artificial Sequence Description of
Artificial Sequence Forward Primer 160 gattgcaacg ctgaagttta tg 22
161 26 DNA Artificial Sequence Description of Artificial Sequence
probe 161 ctgtcaactg tcaaccactg ggaatg 26 162 22 DNA Artificial
Sequence Description of Artificial Sequence Reverse Primer 162
gaggcctttt catcagtgag at 22 163 22 DNA Artificial Sequence
Description of Artificial Sequence Forward Primer 163 aatcttcact
ccaggcacat ag 22 164 24 DNA Artificial Sequence Description of
Artificial Sequence probe 164 acctctgcca gcaaccttga gagg 24 165 22
DNA Artificial Sequence Description of Artificial Sequence Reverse
Primer 165 tcccatcttt cttcttgtcc tt 22 166 18 DNA Artificial
Sequence Description of Artificial Sequence Forward Primer 166
acgcagagcc caggtttt 18 167 27 DNA Artificial Sequence Description
of Artificial Sequence probe 167 tcacctttcc gatcatcacg aataggg 27
168 22 DNA Artificial Sequence Description of Artificial Sequence
Reverse Primer 168 cgcaggacct taggtgacta gt 22 169 22 DNA
Artificial Sequence Description of Artificial Sequence Forward
Primer 169 gattgcaacg ctgaagttta tg 22 170 26 DNA Artificial
Sequence Description of Artificial Sequence probe 170 ctgtcaactg
tcaaccactg ggaatg 26 171 22 DNA Artificial Sequence Description of
Artificial Sequence Reverse Primer 171 gaggcctttt catcagtgag at 22
172 19 DNA Artificial Sequence Description of Artificial Sequence
Forward Primer 172 acagagcatt tggcaagct 19 173 27 DNA Artificial
Sequence Description of Artificial Sequence probe 173 cagtactaca
ccttctgcac agacaca 27 174 20 DNA Artificial Sequence Description of
Artificial Sequence Reverse Primer 174 gttggccctt ctgtcttctc 20 175
18 DNA Artificial Sequence Description of Artificial Sequence
Forward Primer 175 cagccactgg agaatgca 18 176 27 DNA Artificial
Sequence Description of Artificial Sequence probe 176 agcagtacga
aattctccgt ggctacc 27 177 18 DNA Artificial Sequence Description of
Artificial Sequence Reverse Primer 177 gaatgggctc caggtctg 18 178
18 DNA Artificial Sequence Description of Artificial Sequence
Forward Primer 178 acgcagagcc caggtttt 18 179 27 DNA Artificial
Sequence Description of Artificial Sequence probe 179 cacctttccg
atcatcacga atagggg 27 180 25 DNA Artificial Sequence Description of
Artificial Sequence Reverse Primer 180 gggtggactt acagttgttt cttct
25 181 24 DNA Artificial Sequence Description of Artificial
Sequence Forward Primer 181 ctttacttca tgcacttcaa cttg 24 182 30
DNA Artificial Sequence Description of Artificial Sequence probe
182 cctcctacct ttgtgaatat gactatgtga 30 183 23 DNA Artificial
Sequence Description of Artificial Sequence Reverse Primer 183
actctcgaag tgtcctcagt ttc 23 184 22 DNA Artificial Sequence
Description of Artificial Sequence Forward Primer 184 ttttaaaggg
acccactact gg 22 185 25 DNA Artificial Sequence Description of
Artificial Sequence probe 185 ctggcatagc tggcccattg ctcat 25 186 19
DNA Artificial Sequence Description of Artificial Sequence Reverse
Primer 186 gaaaaggcag catccactg 19 187 22 DNA Artificial Sequence
Description of Artificial Sequence Forward Primer 187 agaccaaggc
cactacaaat gt 22 188 23 DNA Artificial Sequence Description of
Artificial Sequence probe 188 cacagatgcc actgtccagg gaa 23 189 22
DNA Artificial Sequence Description of Artificial Sequence Reverse
Primer 189 acctgcactg tgtcctcata gt 22 190 22 DNA Artificial
Sequence Description of Artificial Sequence Forward Primer 190
tcacatgacc tttgactttg tg 22 191 23 DNA Artificial Sequence
Description of Artificial Sequence probe 191 acctcggccc tctggggata
aaa 23 192 22 DNA Artificial Sequence Description of Artificial
Sequence Reverse Primer 192 gaaggaaagg tcagaagagc tt 22 193 21 DNA
Artificial Sequence Description of Artificial Sequence Forward
Primer 193 cctcaaggtg accagtttgt c 21 194 26 DNA Artificial
Sequence Description of Artificial Sequence probe 194 cgcccttcag
acactagagg aaacag 26 195 20 DNA Artificial Sequence Description of
Artificial Sequence Reverse Primer 195 ctcctggatg tggcagataa 20 196
22 DNA Artificial Sequence Description of Artificial Sequence
Forward Primer 196 agagcctgga aattaccaat gt 22 197 26 DNA
Artificial Sequence Description of Artificial Sequence probe 197
agacccgagg atcctccctc agtgat 26 198 22 DNA Artificial Sequence
Description of Artificial Sequence Reverse Primer 198 cagtcaggtg
aaaattccac at 22 199 19 DNA Artificial Sequence Description of
Artificial Sequence Forward Primer 199 ccaagagcgt gtccaggta 19 200
25 DNA Artificial Sequence Description of Artificial Sequence probe
200 agagcaccaa gcgcttcatc aagtg 25 201 19 DNA Artificial Sequence
Description of Artificial Sequence Reverse Primer 201 ctcgttccag
gcgttgtac 19
* * * * *