Generation of single-strand circular DNA from linear self-annealing segments

Abstract

The present invention provides a method for the rapid simultaneous production of a plurality of single-stranded DNA circles having a predetermined size and nucleotide sequence using pre-designed hairpin oligonucleotides containing complementary sequences for directing ligation to form dumbbell-shaped monomers followed by heat denaturation to yield single-stranded DNA circles.

Description

[0001] This application is a divisional of U.S. application Ser. No. 09/723,685, filed 28 Nov. 2000, which claims the priority of U.S. Provisional Application Ser. No. 60/168,511, filed 2 Dec. 1999, the disclosures of which are hereby incorporated by reference in their entirety.

FIELD OF THE INVENTION

[0002] The present invention relates to a process for forming single-stranded circular DNA from single-stranded hairpin segments containing complementary sequences directing spontaneous circularization of said segments with subsequent ligation to form single circles.

BACKGROUND OF THE INVENTION

[0003] Over the past several decades, research into molecular biology has been greatly enhanced by the plethora of new methodologies made available to workers in the field. Such methods have essentially helped to create the newer area of biotechnology and facilitated its emergence onto the commercial playing field. Especially advantageous has been the methods developed for replicating and amplifying short segments of specific DNA sequences so as to facilitate both the preparation of such sequences as well as amplification for the purpose of identifying desired sequences of DNA within a larger sample.

[0004] Most important in this regard has been the development of the polymerase chain reaction (PCR) as a means of exponentially amplifying desired segments of DNA using short primers that flank larger segments whose precise nucleotide sequence is not required to be known. Despite the enormous advantages conferred by such technology, there are certain drawbacks. These include the fact that PCR generates linear duplex sequences of DNA which require denaturation to be converted into single strand as well as further processing if circles are desired. In addition, the various steps of heating and cooling and the different enzymes required for the process make it expensive, time consuming and cumbersome. To respond to these problems, other methodologies have been devised, many of which are essentially modifications of the basic PCR process.

[0005] However, PCR remains inadequate for the rapid and inexpensive production of single-stranded circular DNAs. Such DNAs have found use as probes for various so-called target sequences existing within larger segments of single-stranded DNA. Often, such circles have been synthesized with discrete probe segments complementary to the sequences of the target DNA. In such cases, the circle is first synthesized as a so-called "open circle" and permitted to anneal to complementary sequences on a target single-stranded DNA. Once hybridized, the open circle is ligated to form a so-called padlock that is then used as a means of detecting the target DNA. [See: Nilsson et al., Padlock Probes: Circularizing Oligonucleotides for Localized DNA Detection, Science, 265, 2085-2088 (1994)]

[0006] Single-stranded circular DNA has been found useful in many different areas of biotechnology, both of an experimental as well as commercial nature. One important such use is as a substrate for rolling circle DNA replication. In this procedure, a single-stranded circle of DNA is mixed with a short strand of single-stranded complementary primer DNA and the two separate strands are allowed to anneal. After addition of a DNA polymerase, such as the Klenow fragment, the intact circle is used as a template by the enzyme and then replicated from the 3'-end of the primer strand. After the enzyme has gone around the circular template, it encounters the 5'-end of the primer, which is then displaced from the template strand so that the enzyme continues to move around the circular template while a long, unbroken single strand of DNA is generated. Such single strand has been referred to as single-stranded concatenated DNA (Ruth and Driver, WO 92/01813). The single-stranded circular products of the present invention are ideally suited for use as a substrate in such processes. The product prepared by the method according to the present invention can ultimately yield single-strand concatenated DNA having numerous different sequential segments that can act as probes, detection sites or restriction sites for further processing.

[0007] Heretofore, the products of so-called "rolling circle amplification," or RCA, have been used as binding sequences for probes containing complementary sequences for specific sequences located in target DNA whose presence it was desired to detect. In essence, the result is to amplify sequences contained in the circular template to facilitate detection of sequences contained in a target.

[0008] In addition, RCA has been used (see Ruth and Driver, WO 92/01813) to produce concatenated single-stranded DNA containing repeated sequences complementary to those contained in the single-stranded circular substrates but containing restriction sites. Thus, when the concatenated DNA is treated with restriction enzymes, it is cut into short, repetitive segments which can, if desired, be ligated to form structures complementary to the original circles. With the addition of primers and DNA polymerase, such process can be repeated to form copies of the original circles. The present invention eliminates the need for such multistep processes by duplicating the desired circles at the outset, thus eliminating the need for a second round of RCA.

[0009] Another useful aspect of RCA technology has been to generate circles of different size, combine them, and use these as probes for target DNAs having different target sequences. This has been done either by generating circles of different size and mixing them, or else by running multiple RCA reactions simultaneously in the same reaction mixture, with the relative amounts of starting material determining the relative amounts of products. However, one must first generate the different sized circles to use as substrates.

[0010] The methods according to the present invention eliminate the need for such cumbersome processes by providing an easy and effective means of generating circles of any desired sizes and sequences. Thus, using the methods disclosed herein, it is a simple matter to generate circles all of which have the same size, but whose nucleotide sequences are different, or to generate circles of different size and sequence, or any other conceivable combination, all at the same time. The same DNA polymerase will replicate all of the sequences together and their relative abundance in the product will be a function of their relative abundance in the starting mixture.

[0011] One of the problems of current RCA technology is that most starting circles are synthesized chemically (to facilitate predetermination of the nucleotide sequence or sequences contained within the circles). Such synthesis has made production of circles larger than about 100 bases both costly and time consuming. Of course, circles larger than about 200 nucleotides cannot be effectively prepared using current technology. Conversely, plasmid technology has not been of much use in this area because the needed starting circles must be single-stranded whereas plasmids are normally duplex DNAs.

[0012] Once stretches of single-stranded DNA have been synthesized, the circles are formed enzymatically through the use of ligase enzymes and employing a short guide oligonucleotide. Any remaining unreacted linear oligonucleotide and guide oligonucleotide are then digested with exonucleases. The entire process involves several steps, all of which work with varying efficiencies. The yield of circles by such processes is commonly less than 50% and other, undesired, forms are always present. A simpler and more efficient process for generating such circles is therefore desirable.

BRIEF SUMMARY OF THE INVENTION

[0013] The methods according to the present invention involve a different approach from those described hereinabove. In accordance with the present invention, separate segments of single-stranded DNA, each possessing a first short sequence complementary to a second short sequence within the same oligonucleotide, are allowed to self-anneal, thereby forming a pseudo-circular, or hairpin, oligonucleotide having an overhang composed of a portion of a terminal sequence of said single-stranded DNA.

[0014] It is a further object of the present invention to provide separate pseudocircular (i.e., hairpin) single stranded DNA structures that can readily be ligated to each other to form, after heat denaturation, enlarged single-stranded circular DNAs containing predetermined nucleotide sequences formed from the sequences of the starting segments.

[0015] It is another object of the present invention to provide a method of synthesizing single-stranded circular DNA molecules of varying sizes and sequences using pseudocircular DNA segments as a starting material and without the need for multiple cycles of synthesis and ligation.

[0016] It is also an object of the present invention to produce single-stranded circular DNA having predetermined sequences that can be readily replicated without the need for any linear intermediates.

[0017] It is likewise an object of the present invention to provide a means of producing multiple copies of single-stranded DNA circles of varying sizes and of any desired sequences for subsequent mixing to yield a single reaction mixture for further rolling circle replication.

[0018] It is another object of the present invention to provide a means of synthesizing single-stranded DNA circles capable of ready use in subsequent processes, such as rolling circle amplification.

[0019] It is a still further object of the present invention to provide hairpin oligonucleotides with complementary ends (i.e., complementary overhang regions) that comprise restriction sites for endonucleases to provide, after appropriate ligating and denaturation, single stranded circles whose RCA products can be cut by the same restriction enzyme to regenerate hairpin oligonucleotides, thereby providing, inter alia, an enzymatic source of oligonucleotides for production of circles without the need of chemical synthesis.

[0020] It is also an object of the present invention to provide hairpin oligonucleotides with coherent ends for ligation to DNA restriction fragments of any desired size and sequence to form circles for amplification by RCA.

BRIEF DESCRIPTION OF THE DRAWINGS

[0021] FIG. 1 shows a schematic diagram of the overall process according to the present invention for the simple and rapid production of single stranded DNA circles. Here, two hairpin oligonucleotides, each circularized by internal complementary sequences, are permitted to anneal to each other via complementary overhangs, or coherent tail sequences (here, each with an overhang containing a pentanucleotide complementary 5'-TGTAC-3' (SEQ ID NO: 3) and 5'-GTACA-3' (SEQ ID NO: 4) sequences, or so-called "sticky-ends"). After annealing is complete, the ends of the hairpin oligonucleotides are ligated, either by chemical or enzymatic means, to provide a larger single-stranded DNA circle in the form of a "dumbbell." Of course, the sizes of the starting hairpin oligonucleotides can be pre-determined, as can be the sequences of the circles. Following ligation, the "dumbbell" shaped product is heat denatured to yield a single-stranded circular product which, due to the circular shape, does not re-anneal.

[0022] FIG. 2 shows an example of hairpin oligonucleotide ligation wherein the resulting duplex sequence forms a BamHI restriction nuclease site, with subsequent formation of a single-stranded circle.

[0023] FIG. 3 shows an example of hairpin oligonucleotides that, on ligation, form non-palindromic restriction nuclease sites, here Bbs I, and eventually forming a single-stranded DNA circle using the method disclosed herein.

[0024] FIG. 4 shows an example of ligation of hairpin oligonucleotides to a restriction enzyme fragment, or non-circular duplex DNA with strands W and C and having a single-stranded overhang at each end such that after hybridization with hairpin oligonucleotides, and subsequent ligation, the linear duplex sequences formed thereby represent restriction sites, which sites will be singular following eventual formation of a single-stranded DNA circle following annealing, ligation and heat denaturation. Such sites can then be duplexed at a later stage by hybridization with selected target sequences and used for selective attack by the corresponding restriction nuclease(s). After amplification by rolling circle amplification (RCA) such sites can be duplexed by self-annealing and then cut by the corresponding restriction nuclease(s) to regenerate the original or starting restriction enzyme fragment.

DETAILED DESCRIPTION OF THE INVENTION

[0025] The present invention is directed to a simple and rapid method of synthesizing single-stranded DNA circles of varying size and sequence. The method disclosed according to the present invention makes use of the tendency of complementary DNA sequences to anneal to each other whether present as part of a larger single DNA sequence or when present on different polynucleotides.

[0026] Current technology prepares pre-formed circles for rolling circle amplification (RCA) by ligation of a chemically synthesized oligonucleotide. For ligation, the respective 5'- and 3'-ends are brought together using a short guide oligonucleotide. Unligated linear DNA and the guide oligonucleotides are then digested with a combination of exonucleases. The entire process involves several steps that operate with varying efficiency. Additionally, the yield of circular monomers (i.e., single-stranded DNA circles) can be severely limited by competing reactions (e.g., linear and circular concatamer formation). Thus, some form of optimization is commonly required to improve yield of the monomeric circles. One often used solution is to perform the ligation step at low oligonucleotide concentration. However, this has proven useful only in small scale preparations and has been found unpractical and uneconomical for larger scale, such as commercial, preparations. Other approaches to generate longer circles (e.g., RCA itself and asymmetric PCR) also require a ligation step.

[0027] The methods disclosed herein according to the present invention rely on a more straightforward, though novel, approach. The present invention makes use of the well-known coherent end (or "sticky end") method of joining DNA segments. Briefly, each oligonucleotide is designed to form a short hairpin, or linear duplex segment, followed by an overhang such that the overhang on one hairpin oligonucleotide is complementary to the overhang on another hairpin oligonucleotide thereby resulting in a double hairpin dimer ready for closure by ligation by either enzymatic or chemical means.

[0028] In accordance with the present invention, there are provided predetermined hairpin oligonucleotide sequences containing short stretches of complementary sequences, perhaps as few as 5 or 6 nucleotides, such that these complementary stretches will anneal to provide a hairpin oligonucleotide. As used herein, the term "hairpin oligonucleotide" refers to a single stranded polynucleotide containing complementary sequences at or near each of its 5'- and 3'-ends such that said complementary sequences anneal, resulting in the formation of a circular structure held in the circularized form by the hydrogen bonded internally complementary sequences. The difference between hairpin oligonucleotides and actual single-stranded DNA circles, such as those formed by the methods disclosed herein, is that the single-stranded circles are held together by covalent bonds to form single circles with no internal hybridization and without free 5'- and 3'-ends. In addition, the starting hairpin oligonucleotides disclosed herein contain internal complementary sequences that are inverted relative to each other so that the 3'- and 5'-ends, where said sequences are located, will hybridize within the same segment to yield a short linear segment with only the non-hybridized portion of the polynucleotide forming a circular structure. In addition, only one of said complementary sequences will be located at either the 5'- or 3'-end of the polynucleotide with the other complementary sequence being displaced from the end of said polynucleotide by a short segment of nucleotides that is not complementary to any portion of the polynucleotide of which it is a part.

[0029] A hairpin oligonucleotide that is useful in the methods of the invention comprises a single-stranded oligonucleotide having a short double-stranded portion formed of two self-complementary segments having a loop at one end and a short overhanging single strand at the other so that the ends of said double-stranded portion are not blunt. Thus, for purposes of the present invention, a hairpin may be defined as a double-helical region formed by base-pairing between adjacent, inverted complementary sequences in a single-stranded DNA, preferably within the same single stranded DNA.

[0030] Thus, the present invention is directed to a process for preparing multiple copies of single-stranded circular DNA, comprising contacting 2 or more hairpin oligonucleotides, wherein each hairpin oligonucleotide contains at least one segment that does not hybridize with any segment of the same or another of said hairpin oligonucleotides, and wherein each said hairpin oligonucleotide contains a complementary terminal sequence, under conditions permitting said complementary terminal sequences to hybridize, and then ligating the resulting hybridized hairpin oligonucleotides to form single-stranded dumbbell-shaped DNA monomers (such structure is essentially a monomer comprising a double-stranded linear segment with a loop at each end). Following ligation, the single-stranded dumbbell shaped product is heat denatured by means well known in the art to form a fully open single-stranded DNA circle which, despite the presence of the complementary sequences within the circle, will now no longer anneal and thus will remain a single-stranded circle. Appropriate denaturation conditions commonly require temperatures in the range of 70.degree. C. to as much as 100.degree. C., with temperatures of about 95.degree. C., or at least 95.degree. C., being sufficient for most DNA circles.

[0031] In one embodiment of the present invention, two 100-mer (i.e., 100 base) oligonucleotides, each with a 5 base pair hairpin and a 4 nucleotide overhang, were used to prepare a 200 nucleotide single-stranded circle. In general, the longer the oligonucleotide the longer the hairpin needed to prepare a stable hairpin-loop that can be ligated. Conversely, present chemical technology does not readily facilitate the preparation of single-stranded circular oligonucleotides of longer than about 100 bases in length. Thus, efficiency in chemically synthesizing long single-stranded oligonucleotides, for example, any circles larger than about 70 nucleotides in length, is very low.

[0032] In accordance with one embodiment of the present invention, there is provided a first hairpin oligonucleotide of single-stranded DNA having a general structural arrangement as follows: TABLE-US-00001 5' |--------|-------------------------------------------------------------- --|--------|--------| 3' A B A' C

[0033] Here, A, B, A', and C represent individual segments of nucleotides within a larger polynucleotide such that segments A and A' are complementary to each other in the usual sense, or Watson-Crick sense, with adenine bases hydrogen bonding to thymine bases and guanine bases hydrogen bonding to cytosine bases. However, segments A and A' are complementary only when segment A is read in the 5' to 3' direction and segment A' is read in the 3' to 5' direction. The result of hybridization of segments A and A' is the formation of a hairpin oligonucleotide with a short stretch of linear duplex DNA at one side of the hairpin oligonucleotide with single stranded segment C extending outward from the short linear duplex and away from the rest of the circle. The resulting structure is depicted in FIG. 1.

[0034] A specific embodiment of the hairpin oligonucleotide disclosed according to the present invention may therefore have the following structure: TABLE-US-00002 5' CATGA----------------------------------------------------------TCATG---- ---3' A B A' C

[0035] Here, segment A has the sequence 5'-CATGA-3' (SEQ ID NO: 5) and segment A' has the sequence 5'-TCATG-3' (SEQ ID NO: 6). Segment C is a tail segment that has a sequence pre-selected so as to be different from the sequences complementary to either segments A or A', or even from segment B, thereby preventing any complementarity with those sequences and thus preventing unwanted internal annealing. Segment B is a segment having a pre-determined nucleotide sequence which sequence is to be incorporated into the single-stranded circular DNA formed by operation of the invention disclosed herein. Thus, the sequence of segment B is determined by the desires, inclinations and motivations of the user of the present invention, based on the single-stranded DNA circles one desires to synthesize.

[0036] Also in accordance with this embodiment of the present invention there is provided a second single-stranded DNA hairpin oligonucleotide having the same general structure as the aforementioned first single-stranded DNA hairpin oligonucleotide. In general, the sequences of the individual segments of the second hairpin oligonucleotide will be different from, and unrelated to, the sequences of the segments of the first hairpin oligonucleotide, with the exception of segment C. The sequence of segment C of the first hairpin oligonucleotide and the sequence of segment C of the second hairpin oligonucleotide are complementary to each other but only when read in opposite directions. For example, if the sequence of segment C of hairpin oligonucleotide 1 has the sequence: 5'-TGTAC-3' (SEQ ID NO: 3) then the sequence of segment C of hairpin oligonucleotide 2 will have the sequence: 5'-GTACA-3' (SEQ ID NO: 4).

[0037] In practicing the methods of the present invention it is unnecessary for segment C of each of the hairpin oligonucleotides to be at the 3'-end of the hairpin oligonucleotide but, instead, each segment C could occur at the 5'-end of each of the hairpin oligonucleotides with no effect on the success of the methods disclosed herein. The only requirement is that these segments be complementary when read in opposite directions and that they both occur at either the 3' ends of the hairpin oligonucleotides or at the 5'-ends of the hairpin oligonucleotides but, for the present invention to operate, the respective segments C must not occur at the 5'-end of the first hairpin oligonucleotide and at the 3'-end of the second hairpin oligonucleotide, or vice versa.

[0038] In accordance with the present invention, segment B of each hairpin oligonucleotide will comprise, or a portion of such segment will commonly comprise, a pre-determined nucleotide sequence to be incorporated into a single-stranded DNA circle. Said pre-determined sequence will have a nucleotide sequence dictated by the needs and desires of the user of the methods disclosed herein. Such pre-determined sequence may be a sequence derived from a naturally occurring polynucleotide, such as from a plasmid or the genome of an organism, or may be a wholly novel sequence, including a novel sequence synthesized de novo expressly for incorporation into single-stranded circles.

[0039] In keeping with one embodiment of the present invention, segment B of each of the first and second starting hairpin oligonucleotides may have the same nucleotide sequence, or similar sequences, but the sequences of these segments will commonly differ. Thus, a reaction mixture may contain one or more copies, commonly many copies, of a first hairpin oligonucleotide containing a segment B having a pre-determined nucleotide sequence, and one or more copies, commonly many copies, of a second hairpin oligonucleotide containing a segment B having the same or, commonly, a different, nucleotide sequence.

[0040] In one embodiment of the present invention, a reaction medium will contain a mixture of hairpin oligonucleotides comprised of at least two types. The first type, or population, of hairpin oligonucleotides will have the general structure already described, with a pre-determined sequence, located in segment B, that may or may not be a sequence of interest to the user. The second type, or population, of hairpin oligonucleotides will contain a segment B having a pre-determined sequence whose incorporation into single-stranded circles is desired. Further, the first and second populations of hairpin oligonucleotides will be so structured that their overhang sequences (designated segment C herein) will be complementary and will hybridize upon mixing of the two populations of hairpin oligonucleotides. Thus, segment C in any hairpin oligonucleotide from population 1 will be the same but different from the sequence of segment C from any of the hairpin oligonucleotides of population 2, and vice versa.

[0041] In a further embodiment of the present invention, a reaction medium will contain 3 or more populations of hairpin oligonucleotides, one of which will contain a segment B with a pre-determined nucleotide sequence that may, but need not, be essential to the nature of the single-stranded circular products to be formed. Conversely, the other populations of hairpin oligonucleotides will differ solely in the sequence of segment B as described herein. In one such embodiment, there may be 3 such populations wherein each will differ in the sequence of its respective segment B. In this case, hairpin oligonucleotides of population 1 will all have the same sequence for segment C whereas populations 2and 3 will all have the same sequence for segment C but this sequence will be complementary to that of segment C of population 1. Thus, upon mixing the 3 populations, hairpin oligonucleotides of population 1 will hybridize through segment C with the corresponding complementary segment C of the hairpin oligonucleotides of populations 2 and 3 to form 2 distinct populations of single stranded DNA circles, each product circle being formed from a hairpin oligonucleotide from population 1 and 2 or from population 1 and 3. Because of the identity of the sequence of segment C, hairpin oligonucleotides of population 1 cannot hybridize to other hairpin oligonucleotides of population 1. Because hairpin oligonucleotides of populations 2 and 3 have the same sequence for their own segments C, hairpin oligonucleotides from populations 2 and 3 cannot hybridize to each other but only with hairpin oligonucleotides of population 1.

[0042] In keeping with the method of the present invention, another embodiment can have 4 populations of hairpin oligonucleotides. In this case, a reaction mixture would contain, for example, many copies of hairpin oligonucleotides of population 1, containing unique DNA sequences for segments B and C. Conversely, populations 2, 3, and 4 will each contain hairpin oligonucleotides with unique sequences for their respective segments B but each will have the same sequence for their respective segments C, which sequence will be complementary to the sequence of segment C of the hairpin oligonucleotides of population 1.

[0043] By continuing with this process, all manner of combinations and permutations of the hairpin oligonucleotides disclosed according to the present invention can be used to form any desired number of unique single-stranded DNA circles.

[0044] In accordance with the present invention, the starting populations of hairpin oligonucleotides need not only differ in sequence but, of course, in size and relative concentration. Thus, for example, in the case of 5 populations of hairpin oligonucleotides, population 1 will be of whatever sequence and size is dictated by the needs, inclinations and motivations of the researcher, or other user, while populations 2, 3, 4, and 5 will likewise contain sequences, and be of whatever sizes, the researcher, or other user, desires. Further, the individual concentrations of populations 2, 3, 4, and 5 will likewise be those dictated by the exigencies of the experiments, or other procedures, requiring the synthesis of single-stranded DNA circles. Of course, the relative concentrations of the unique single-stranded DNA circular products will correspond to the relative concentrations of the unique starting hairpin oligonucleotides. In carrying out the methods disclosed herein, it will thus be essential to insure sufficient amounts of hairpin oligonucleotides of population 1 so as to secure complete reaction of the hairpin oligonucleotides of the other populations. Thus, hairpin oligonucleotides of population 1 can be essentially a kind of "universal" hairpin oligonucleotide available merely for forming a circle with other hairpin oligonucleotides whose sequences and sizes are more essential to the nature of the single-stranded DNA circles whose production is desired.

[0045] Thus, according to the method disclosed herein, the populations of hairpin oligonucleotides will differ mainly in the nucleotide sequence of their respective segments B. Thus, each pre-selected segment B, or pre-selected sequence forming a portion of segment B, may be the same or different. If all such sequences are the same, then the result of applying the method of the present invention will be to generate many copies of the same sequence with each round and give rise to multiple copies of identical single-stranded DNA circles. Alternatively, if the pre-selected sequences forming, or which are part of, segment B within the hairpin oligonucleotides of the different populations are different in sequence and/or size, the result of applying the method of the present invention will be to generate equimolar quantities of multiple copies of single-stranded DNA circles containing each of the pre-selected sequences with the circles corresponding to each of the selected segments being of either the same size but different in sequence, or different in both size and sequence. The number and nature of the products produced by the method of the present invention are therefore limited only by the desires and motivations of the user.

[0046] The hairpin oligonucleotides used as starting materials in the methods of the present invention may be prepared synthetically, using either automation or conventional chemistry, for example by attaching a starting structure to beads and adding nucleotides thereto. The hairpin oligonucleotides for use in the present invention may also be prepared by synthesizing segments or fragments thereof and then joining said segments or fragments into larger structures containing appropriate nucleotide sequences for use herein. Such segments or fragments may also be of natural origin, deriving from microorganisms in nature or the result of cloning of sequences within selected organisms and utilizing selected vectors for the cloning process. Such segments or fragments may also derive from natural vectors, such as plasmids, viruses, or the like.

[0047] The hairpin oligonucleotides for use in the present invention may also be hybrids, or chimeras, containing some segments or sequences that are of natural origin as well as segments or sequences wholly synthetic in origin. Of course, the fact that a given segment or sequence is found in nature does not prevent it from being prepared synthetically in the laboratory for use herein. Thus, the sources available for the hairpin oligonucleotides, or fragments, or segments, or portions thereof, for use in the present invention are left to the skill and imagination of the researcher, or other user of the present invention.

[0048] As used herein, the terms "portion," "segment," and "fragment," when used in relation to polynucleotides or oligonucleotides of any kind, including the hairpin oligonucleotides described herein, refer to a continuous sequence of nucleotide residues, which sequence forms a subset of a larger sequence. For example, if a polynucleotide were subjected to treatment with any of the common endonucleases, the oligonucleotides resulting from such treatment would represent portions, segments or fragments of the starting polynucleotide(s).

[0049] Following hybridization of the complementary, or cohesive, ends of hairpin oligonucleotides to form pairs like those depicted in FIG. 1, the sequences of the respective hybridized hairpin oligonucleotides are then closed using any of several forms of DNA ligation. Such ligation can involve a reaction catalyzed by an enzyme, including any of several well known, and often used, DNA ligases, such as T4 ligase or E. coli ligase, or Ampligase, or can involve no enzymes and, instead, comprise a simple chemical reaction, such as that used in DNA synthetic procedures, for example, reactions involving phosphorothioate derivatives or other reactive groups. The latter, of course, may prove more cumbersome than a simple enzyme reaction.

[0050] For ligation employing an enzyme-catalyzed reaction, a general procedure can involve combining 50 pmol (1 pmol=1 picomole or 10.sup.-12 moles) of one prepared population of hairpin oligonucleotides with 50 pmol of a second population, or any number of populations such that the total amount of DNA is about 100 pmol. The hairpin oligonucleotides are at this time suspended in ligase buffer (50 mM Tris-Cl, 1 mM MgCl.sub.2, and 1 mM dithiothreitol, 0.1 mM ATP, pH 7.6) at 0.degree. C. until addition of ligase. Hybridization of the hairpin oligonucleotides can, of course, be allowed to occur during the ligation reaction so that the enzyme ligates the cohesive, or sticky, ends as hybridization proceeds. A preferred DNA ligase is that of phage T4, which requires ATP (adenosine triphosphate) for its reaction (already contained in the above-recited ligase buffer). If E. coli ligase is used instead, NAD.sup.+ (nicotinimide adenine dinucleotide) must be used in place of ATP. If reaction volume is a total of 10 .mu.L, then the ligase reaction commences with the addition of 3 Weiss units of T4 DNA ligase, incubated at about 37.degree. C. for about 3 hours, a time period that will vary with cohesive ends and with other parameters so that this must be optimized by the researcher to obtain the best results. In any event, incubation temperatures will generally be between 4.degree. C. and about 65.degree. C. Optionally, the buffers can be prepared at higher concentration and then diluted with a suitable amount of water.

[0051] In carrying out the procedures of the present invention it is of course to be understood that reference to particular buffers, media, reagents, cells, culture conditions and the like are not intended to be limiting, but are to be read so as to include all related materials that one of ordinary skill in the art would recognize as being of interest or value in the particular context in which that discussion is presented. For example, it is often possible to substitute one buffer system or culture medium for another and still achieve similar, if not identical, results. Those of skill in the art will have sufficient knowledge of such systems and methodologies so as to be able, without undue experimentation, to make such substitutions as will optimally serve their purposes in using the methods and procedures disclosed herein.

[0052] In addition to ligation using enzymes, chemical methods are also available for use with the present invention. These include, for example, the formation of phosphorothioate derivatives of terminal nucleotide residues and subsequent ligation. Such methods are well known in the literature, being commonly used for nucleotide synthesis. [See: U.S. Pat. No. 5,859,232 and U.S. Pat. No. 5,151,510 (and references contained therein) for synthetic procedures]

[0053] Consequently, the method disclosed according to the present invention allows single-step generation of various sized circles of DNA having uniquely known (i.e., either pre-determined or pre-selected) sequences. The synthesis of such a product is therefore ideal for producing preformed circles for multiplexing RCA (rolling circle amplification). Also, because the sequences of the starting DNA are known, it is a straightforward matter to produce primers and probes specific for each of the circles. Further, circles are produced at the outset and not linear sequences of DNA that must still be ligated before proceeding further. In accordance with the present invention, enzymatic ligation can proceed at the same time, and in the same reaction mixture, as the initial hybridization step.

[0054] The circles made by the invention are frequently used for signal amplification by RCA. For example, a target DNA/RNA sequence is recognized by a bifunctional oligonucleotide which also serves as a primer for RCA using a circle made by the invention. Since many different circles are made simultaneously it is possible to detect multiple targets in a single sample at once. Many other and different uses for the single-stranded circles produced according to the methods of the invention are described in the Ruth and Driver reference cited above (WO 92/01813).

[0055] In accordance with the present invention, targets are detected by rolling circle amplification (or RCA). Such targets can be any molecules that can be detected using RCA methods, including DNA, RNA and proteins. Thus, for example, proteins can be employed by using an antibody conjugated to an oligonucleotide. DNA/RNA targets can be employed using bifunctional oligonucleotides. One arm of the bifunctional oligonucleotide recognizes and anneals to the target whereas the other arm acts as a primer for RCA. Thus, any molecule that can be tagged with an oligonucleotide can then be detected by RCA methodology using circles made according to the present invention.

[0056] The single-stranded DNA circles made according to the invention find a variety of other uses. In particular, they are substrates for further rolling circle amplification. In one such embodiment, a target DNA or RNA sequence present in a biological sample is recognized by a bifunctional oligonucleotide, which oligonucleotide then serves as a primer for rolling circle amplification using the single stranded circles made according to the invention as template. Since many different circles can be made, the methods of the invention facilitate the detection of multiple targets in a single sample (referred to as multiplexing). In this way, the relative concentration of targets in a biological sample can be detected since such molecules will serve to replicate the different single-stranded circles in proportion to the level of target in the test sample, the latter process being carried out by conventional rolling circle amplification. Such conventional rolling circle amplification can be effected by a variety of commonly available enzymes, including E. coli DNA polymerase I, Klenow fragment, T4 or T7 DNA polymerases, Taq polymerase, and others.

[0057] Also in accordance with the present invention, the double-stranded linear segment formed from the ligation of the hairpin oligonucleotides comprises at least one substrate sequence for at least one restriction endonuclease (see FIGS. 2 and 3 for specific examples).

[0058] Also in accordance with the present invention, the mixture of hairpin oligonucleotides can also comprise a non-circular DNA duplex segment, formed by direct chemical synthesis or by the action of one or more restriction nucleases on a larger circular or non-circular DNA structure and wherein said non-circular, or linear, duplex DNA segment contains at least one linear terminal sequence complementary to at least one hairpin oligonucleotide complementary terminal sequence and wherein following ligation the resulting double-stranded linear segment of the aforementioned dumbbell shaped product contains said non-circular duplex DNA between said two circular portions.

[0059] In a preferred embodiment, a non-circular DNA duplex segment has a linear terminal sequence at each end wherein each said terminal sequence is complementary to a hairpin oligonucleotide complementary terminal sequence.

[0060] In accordance with the present invention, hybridization of a hairpin oligonucleotide with a linear terminal sequence of the non-circular DNA duplex forms, or completes formation of, a restriction nuclease substrate sequence. Thus, in a preferred embodiment the double-stranded linear segment resulting from ligation of said non-circular DNA duplex segment and hairpin oligonucleotides comprises a restriction nuclease substrate sequence.

[0061] In another preferred embodiment, the double-stranded linear segment resulting from ligation of said non-circular DNA duplex segment and hairpin oligonucleotides comprises two restriction nuclease substrate sequences.

[0062] In one embodiment, hairpin oligonucleotides can be ligated to the ends of DNA restriction fragments of any desired size and sequence identity and then used to prepare circles. In a preferred embodiment, a segment of DNA is cut using a known restriction enzyme and the coherent ends used for ligation to a hairpin oligonucleotide (See FIG. 4). To avoid self-ligation, two different restriction nucleases can be used, each producing a different but known coherent end. Following the heat denaturation step of the present invention, a circle is formed. In one highly preferred embodiment, this method is used to amplify unknown sequences by RCA since the ligated hairpin oligo can be utilized for RCA priming. The only sequence information required for such a procedure is the identity of the overhangs of the restriction fragment (which are always known since these are defined by the user in choosing the restriction nucleases used to form them). Such methods can be readily used to amplify unknown genomic DNA, viral DNA, as well as cDNA libraries. RCA amplified DNA can then be used directly for sequencing or it can be cloned. In fact, the starting fragment and oligonucleotide could even be regenerated after amplification by digesting the RCA product with the original restriction enzyme(s).

[0063] Advantages of such a procedure include the fact that the sequences are replicated in proportion to their occurrence in the substrate mixture, detection of target sequences is independent of the structure of the sequence, and further that the detection of the relative amounts of multiple molecules of interest is facilitated.

[0064] Of course, for use in the methods disclosed and claimed herein, it is unnecessary for the linear segment of DNA to be produced by restriction nuclease, since direct chemical synthesis thereof is a completely suitable option for producing such segments. For example, in FIG. 4, the non-circular duplex DNA, or linear segment composed of at least partially complementary strands C and W, can be generated by application of one or more restriction nucleases to a larger segment, circular or non-circular, of DNA to form said non-circular, or linear, duplex DNA. In addition, said non-circular duplex DNA can be formed by direct chemical synthesis to form said duplex segment. Further, for use in the methods of the present invention, such non-circular duplex DNA need not necessarily incorporate any restriction nuclease sites or may optionally incorporate a restriction nuclease site other than at the ends of such non-circular duplex DNA segment, such as in the middle of such segment and wherein such structure may or may not contain one or more such sites at or near the ends of such segment.

[0065] Furthermore, the non-circular duplex DNA segments, such as is disclosed in FIG. 4, as one example, may have single-stranded overhangs at one or both ends and having selected sequences such that, when hybridized to the overhangs of other DNA segments, either other non-circular duplex DNA segments and/or hairpin oligonucleotides, will form duplex restriction nuclease sites following ligation thereof in accordance with the methods disclosed herein. It should be borne in mind that, while interaction of two hairpin oligonucleotides and a single non-circular duplex DNA segment is depicted in FIG. 4, other and different combinations will no doubt suggest themselves to those of skill in the art yet still fall within the bounds contemplated by the present invention.

[0066] While avoiding numerous disadvantages, the method of the present invention affords numerous advantages in the preparation of single-stranded circular DNAs. First, it represents a method to directly generate circles, since all current methods involve ligation (either by chemical or enzymatic means) of linear oligonucleotides. Thus, current methodology is highly inefficient and requires the use of a battery of other enzymes or chemical steps. Conversely, with the methodology disclosed herein, such circles are generated immediately and directly from a predetermined reactant with no need for further processing or enzymatic treatments. In addition, the method of the present invention affords the only means of simultaneously generating any desired number of different (in size or sequence) circles, for multiplexing and other uses, and with no size limitations on the products to be formed. For example, using the methods disclosed herein it is a simple matter to prepare single-stranded DNA circles of sizes anywhere from 50 bases to greater than 5,000 bases, and any manner of combinations in between.

[0067] In one embodiment of the present invention, there are provided hairpin oligonucleotides with complementary ends (i.e., complementary overhang regions) that comprise restriction sites for endonucleases to provide, after appropriate ligating and denaturing, single stranded circles whose RCA products can be cut by the same restriction enzyme to regenerate hairpin oligonucleotides, thereby providing, inter alia, an enzymatic source of oligonucleotides for production of circles without the need of chemical synthesis (see FIGS. 2 and 3). As opposed to the situation with hairpin oligonucleotides having phosphorothioate derivatives protecting the restriction site, the present invention provides an enzymatic factory for simultaneous RCA, cutting and ligating.

[0068] In utilizing the methods disclosed herein, all the circles will share one pair of common short sequences that combine the remnants of the terminal sequence complementary and the complementary sequence forming the hairpin region, now separated from each other in the larger circle (see FIG. 1), which can then be used for priming (for example, for RCA, or rolling circle amplification, or sequencing) using a primer complementary to one of the sequences, or a pair of complementary primers each complementary to one or the other of the sequences present in the single stranded circles.

[0069] The present invention also relates to a kit containing a sample of the aforementioned neutral or reference hairpin oligonucleotides having a defined nucleotide sequence and containing a specified terminal sequence for hybridization and ligation to hairpin oligonucleotides of pre-determined sequence and useful for forming single-stranded DNA circles. The hairpin oligonucleotides of pre-determined sequence can then be designed so as to have segment C regions with sequences complementary to the specified segment C sequences of the neutral or reference hairpin oligonucleotides. Such a kit may optionally contain a sample of T4 ligase for use in carrying out the ligation part of the methods disclosed herein. Such kit may also optionally contain a sample of ligase buffer, as disclosed herein, said buffer being present in powdered form, possibly in a concentrated state, and ready for immediate reconstitution with water. Where said buffer powder is present in a concentrated form, this may preferably be a form containing sufficient buffer salt components so that, when reconstituted with water, the resulting buffer concentration will be higher, perhaps 10 fold higher, than the concentration of said buffer components in the final reaction mixture. Such concentrated form of the buffer can thereby serve as a reservoir for adjusting the pH of said buffer solution concentrate, which concentrated solution merely awaits dilution with water to form the actual reaction mixture. In one embodiment, the method disclosed herein would be carried out by adding the appropriate amounts of the hairpin oligonucleotides to a microfuge tube, or other suitable container, adding the required number of units of ligase, suspending in 1 .mu.L of ice cold buffer concentrate and then commencing reaction by addition of the appropriate volume of distilled water at or near the desired reaction temperature so as to achieve a total volume of the aforementioned 10 .mu.L (or whatever volume is proportionately appropriate to the amounts of DNA and ligase the researcher requires).

[0070] In a further embodiment of the present invention, the neutral or reference hairpin oligonucleotide may itself be designed so as to contain specific reference, or marker, sequences of nucleotides that are subsequently incorporated into the resulting single-stranded DNA circles and can serve as marker sequences for said circles, available for a variety of uses such as providing a binding site for a universal primer sequence useful in subsequent rolling circle amplification of the single-stranded DNA circles. Thus, all of the resulting single-stranded DNA circles would be amenable to replication (i.e., amplification) using the same primer sequence (a sample of such primer may optionally be supplied with the kit). This would avoid the need for the user of the present invention to incorporate a primer target sequence in each of the preformed hairpin oligonucleotides containing the pre-selected sequences of segment B. Such primer target sequence would be incorporated into the single-stranded DNA circles via the neutral or reference or universal hairpin oligonucleotides common to the reaction with the "user-defined" hairpin oligonucleotide(s) containing the pre-selected sequence(s) of segment B.

[0071] In some cases it may be desirable to utilize more than one kind of "user-defined" hairpin oligonucleotide, such as for eventual multiplexing using the resulting single-stranded DNA circles. In such case, it would be important that the relative concentrations of the resulting single-stranded DNA circle populations reflect the relative concentrations of the starting user-defined hairpin oligonucleotides (and their contained pre-selected sequences of interest in their respective B segments). Because of the excess of neutral or reference or universal hairpin oligonucleotides, some of the latter will remain unreacted. To avoid any interference by this population of unreacted hairpin oligonucleotides, the present method, by providing circular products larger than these unreacted components, facilitates ready size separation to yield only reacted circles in direct proportion to the relative concentrations of the starting user-defined hairpin oligonucleotides.

[0072] A specific embodiment of the method of the present invention is described in the following non-limiting example. In following the procedure disclosed in the example it is to be clearly kept in mind that other and different embodiments of the methods disclosed according to the present invention will no doubt suggest themselves to those of skill in the relevant art.

EXAMPLE

[0073] TABLE-US-00003 Oligonucleotide 1 (50 n) 5'-TGAGCTGTAACTTGTCTCGTATTAAACTAAAGCT SEQ ID NO: 1 GAGATCTCACGTACA Oligonucleotide 2 (45 n) 5'-ACTCAATATAGTTCTTGGAGAAGGTGGAATCACA SEQ ID NO: 2 CTGAGTTGTAC

[0074] Oligonucleotides 1 and 2 were mixed at 5 .mu.M each in a 1 ml reaction mixture containing 50 mM Tris-HCl (pH 7.5), 10 mM MgCl.sub.2, 10 mM dithiothreitol (DTT), 1 mM adenosine triphosphate (ATP) and 25 .mu.g/ml bovine serum albumin (BSA). The mixture was heated to 65.degree. C. for 5 minutes and allowed to cool at room temperature (24.degree. C.) for 30 minutes. Ligation was initiated by adding T4 DNA ligase to a final concentration of 2,000 ligation units per ml (approximately 30 Weiss units). The ligation mixture was incubated in a water bath for 2 hours at 37.degree. C. Ligation products were analyzed and quantitated by denaturing polyacrylamide gel electrophoresis.

[0075] To purify circles, 2,000 units of Exonuclease III were added to reaction mixture and incubation continued for 2 hours at 37.degree. C. The mixture was then heated at 95.degree. C. for 5 minutes to inactivate T4 DNA ligase and Exonuclease III and melt any remaining hairpins present in the unligated, linear oligonucleotides. To complete digestion of linear oligonucleotide the reaction mixture was adjusted by adding 66 .mu.l of 1 M glycine-NaOH buffer (pH 9.5) and 8 .mu.l of 1 M DTT and 55 units of Exonuclease V were added. The reaction was incubated at 37.degree. C. for at least one hour and was then deproteinized by digestion with 50 .mu.g/ml Proteinase K for one hour at 37.degree. C. followed by extraction with 1 ml of phenol:chloroform:isoamylalcohol (25:24:1). The circle DNA was then precipitated by adding 0.5 ml of 7.5 M ammonium acetate and 3.75 ml of 100% ethanol and incubation at -20.degree. C. overnight. The circle DNA was collected by centrifugation in a microfuge at maximum speed for 20 minutes at 4.degree. C. The DNA pellet was rinsed once with 70% ice-cold ethanol and dried under vacuum. Circle DNA was finally resuspended in 10 mM Tris-HCl (pH 7.5), 1 mM EDTA to a concentration of 1-5 .mu.M. The circle DNA was heat denatured to full single stranded form by incubating at 100.degree. C. for 5 minutes followed by quick cooling to 4.degree. C. in a water/ice bath.

Sequence CWU 1

1

93 1 2981 DNA Homo sapiens CDS (202)...(2826) 1 cacgaggccg gcggcagaac gcagctgcgg cggctgcggg tctcgtgggg gcggagcggt 60 cgccgctgcc gccgcagctc gggtcgggat ttgaaagatt agaaacttcg ggtggagagg 120 gcggcggcgt tgaatgtgtg gcggaagcgc tgggggtcac ggctccgcgc gccgccggac 180 agccggcggc gtctccacag c atg aat tac ccg ggc cgc ggg tcc cca cgg 231 Met Asn Tyr Pro Gly Arg Gly Ser Pro Arg 1 5 10 agc ccc gag cat aac ggc cga ggc ggc ggc ggc ggc gcc tgg gag ctg 279 Ser Pro Glu His Asn Gly Arg Gly Gly Gly Gly Gly Ala Trp Glu Leu 15 20 25 ggc tca gac gcg agg cca gcg ttc ggc ggc ggc gtc tgc tgc ttc gag 327 Gly Ser Asp Ala Arg Pro Ala Phe Gly Gly Gly Val Cys Cys Phe Glu 30 35 40 cac ctg ccc ggc ggg gac ccg gac gac ggc gac gtg ccc ctg gcc ctg 375 His Leu Pro Gly Gly Asp Pro Asp Asp Gly Asp Val Pro Leu Ala Leu 45 50 55 ctg cgc ggg gaa ccc ggg ctg cat ttg gcg ccg ggc acc gac gac cac 423 Leu Arg Gly Glu Pro Gly Leu His Leu Ala Pro Gly Thr Asp Asp His 60 65 70 aac cac cac ctc gcg ctg gac ccc tgc ctc agt gac gag aac tat gac 471 Asn His His Leu Ala Leu Asp Pro Cys Leu Ser Asp Glu Asn Tyr Asp 75 80 85 90 ttt agc tcc gcc gag tcg ggc tcc tcg ctg cgc tac tac agc gag ggt 519 Phe Ser Ser Ala Glu Ser Gly Ser Ser Leu Arg Tyr Tyr Ser Glu Gly 95 100 105 gag agc ggc ggc ggc ggc ggc ggc agc tcc ttg tcg ctg cat ccg ccg 567 Glu Ser Gly Gly Gly Gly Gly Gly Ser Ser Leu Ser Leu His Pro Pro 110 115 120 cag cag cct ccg ctg gtc ccg acg aac tcg ggg ggc ggc ggc gcg aca 615 Gln Gln Pro Pro Leu Val Pro Thr Asn Ser Gly Gly Gly Gly Ala Thr 125 130 135 gga ggg tcc ccc ggg gaa agg aaa cgt acc cgg ctt ggc ggc ccg gcg 663 Gly Gly Ser Pro Gly Glu Arg Lys Arg Thr Arg Leu Gly Gly Pro Ala 140 145 150 gcc cgg cac cgc tat gag gta gtg acg gag ctg ggc ccg gag gag gta 711 Ala Arg His Arg Tyr Glu Val Val Thr Glu Leu Gly Pro Glu Glu Val 155 160 165 170 cgc tgg ttc tac aag gag gac aag aag acc tgg aag ccc ttc atc ggc 759 Arg Trp Phe Tyr Lys Glu Asp Lys Lys Thr Trp Lys Pro Phe Ile Gly 175 180 185 tac gac tcg ctc cgc atc gag ctc gcc ttc cgg acc ctg ctg cag acc 807 Tyr Asp Ser Leu Arg Ile Glu Leu Ala Phe Arg Thr Leu Leu Gln Thr 190 195 200 acg ggt gcc cgg ccc cag ggc ggg gac cgg gac ggc gac cat gtg tgc 855 Thr Gly Ala Arg Pro Gln Gly Gly Asp Arg Asp Gly Asp His Val Cys 205 210 215 tcc ccc acg agc cca gcc tcc agt tcc gga gaa gat gac gat gag gac 903 Ser Pro Thr Ser Pro Ala Ser Ser Ser Gly Glu Asp Asp Asp Glu Asp 220 225 230 cgc gcc tgc ggc ttc tgc cag agt acg acg ggg cac gag ccg gag atg 951 Arg Ala Cys Gly Phe Cys Gln Ser Thr Thr Gly His Glu Pro Glu Met 235 240 245 250 gtg gag ctt gtg aac atc gag cct gtg tgc gtg cgg ggc ggc ctc tac 999 Val Glu Leu Val Asn Ile Glu Pro Val Cys Val Arg Gly Gly Leu Tyr 255 260 265 gag gtg gat gtg acc caa gga gag tgc tac ccg gtg tac tgg aac cag 1047 Glu Val Asp Val Thr Gln Gly Glu Cys Tyr Pro Val Tyr Trp Asn Gln 270 275 280 gct gat aaa ata cca gta atg cgt gga cag tgg ttt att gac ggc act 1095 Ala Asp Lys Ile Pro Val Met Arg Gly Gln Trp Phe Ile Asp Gly Thr 285 290 295 tgg cag cct cta gaa gag gaa gaa agt aat tta att gag caa gaa cat 1143 Trp Gln Pro Leu Glu Glu Glu Glu Ser Asn Leu Ile Glu Gln Glu His 300 305 310 ctc aat tgt ttt agg ggc cag cag atg cag gaa aat ttc gat att gaa 1191 Leu Asn Cys Phe Arg Gly Gln Gln Met Gln Glu Asn Phe Asp Ile Glu 315 320 325 330 gtg tca aaa tcc ata gat gga aaa gat gct gtt cat agt ttc aag ttg 1239 Val Ser Lys Ser Ile Asp Gly Lys Asp Ala Val His Ser Phe Lys Leu 335 340 345 agt cga aac cat gtg gac tgg cac agt gtg gat gaa gta tat ctt tat 1287 Ser Arg Asn His Val Asp Trp His Ser Val Asp Glu Val Tyr Leu Tyr 350 355 360 agt gat gca aca aca tct aaa att gca aga aca gtt acc caa aaa ctg 1335 Ser Asp Ala Thr Thr Ser Lys Ile Ala Arg Thr Val Thr Gln Lys Leu 365 370 375 gga ttt tct aaa gca tca agt agt ggt acc aga ctt cat aga ggt tat 1383 Gly Phe Ser Lys Ala Ser Ser Ser Gly Thr Arg Leu His Arg Gly Tyr 380 385 390 gta gaa gaa gcc aca tta gaa gac aag cca tca cag act acc cat att 1431 Val Glu Glu Ala Thr Leu Glu Asp Lys Pro Ser Gln Thr Thr His Ile 395 400 405 410 gta ttt gtt gtg cat ggc att ggg cag aaa atg gac caa gga aga att 1479 Val Phe Val Val His Gly Ile Gly Gln Lys Met Asp Gln Gly Arg Ile 415 420 425 atc aaa aat aca gct atg atg aga gaa gct gca aga aaa ata gaa gaa 1527 Ile Lys Asn Thr Ala Met Met Arg Glu Ala Ala Arg Lys Ile Glu Glu 430 435 440 agg cat ttt tcc aac cat gca aca cat gtt gaa ttt ctg cct gtt gag 1575 Arg His Phe Ser Asn His Ala Thr His Val Glu Phe Leu Pro Val Glu 445 450 455 tgg cgg tca aaa ctt act ctt gat gga gac act gtt gat tcc att act 1623 Trp Arg Ser Lys Leu Thr Leu Asp Gly Asp Thr Val Asp Ser Ile Thr 460 465 470 cct gac aaa gta cga ggt tta agg gat atg ctg aac agc agt gca atg 1671 Pro Asp Lys Val Arg Gly Leu Arg Asp Met Leu Asn Ser Ser Ala Met 475 480 485 490 gac ata atg tat tat act agt cca ctt tat aga gat gaa cta gtt aaa 1719 Asp Ile Met Tyr Tyr Thr Ser Pro Leu Tyr Arg Asp Glu Leu Val Lys 495 500 505 ggc ctt cag caa gag ctg aat cga ttg tat tcc ctt ttc tgt tct cgg 1767 Gly Leu Gln Gln Glu Leu Asn Arg Leu Tyr Ser Leu Phe Cys Ser Arg 510 515 520 aat cca gac ttt gaa gaa aaa ggg ggt aaa gtc tca ata gta tca cat 1815 Asn Pro Asp Phe Glu Glu Lys Gly Gly Lys Val Ser Ile Val Ser His 525 530 535 tcc ttg gga tgt gta att act tat gac ata atg act ggc tgg aat cca 1863 Ser Leu Gly Cys Val Ile Thr Tyr Asp Ile Met Thr Gly Trp Asn Pro 540 545 550 gtt cgg ctg tat gaa cag ttg ctg caa aag gaa gaa gag ttg cct gat 1911 Val Arg Leu Tyr Glu Gln Leu Leu Gln Lys Glu Glu Glu Leu Pro Asp 555 560 565 570 gaa cga tgg atg agc tat gaa gaa cga cat ctt ctt gat gaa ctc tat 1959 Glu Arg Trp Met Ser Tyr Glu Glu Arg His Leu Leu Asp Glu Leu Tyr 575 580 585 ata aca aaa cga cgg ctg aag gaa ata gaa gaa cgg ctt cac gga ttg 2007 Ile Thr Lys Arg Arg Leu Lys Glu Ile Glu Glu Arg Leu His Gly Leu 590 595 600 aaa gca tca tct atg aca caa aca cct gcc tta aaa ttt aag gtt gag 2055 Lys Ala Ser Ser Met Thr Gln Thr Pro Ala Leu Lys Phe Lys Val Glu 605 610 615 aat ttc ttc tgt atg gga tcc cca tta gca gtt ttc ttg gcg ttg cgt 2103 Asn Phe Phe Cys Met Gly Ser Pro Leu Ala Val Phe Leu Ala Leu Arg 620 625 630 ggc atc cgc cca gga aat act gga agt caa gac cat att ttg cct aga 2151 Gly Ile Arg Pro Gly Asn Thr Gly Ser Gln Asp His Ile Leu Pro Arg 635 640 645 650 gag att tgt aac cgg tta cta aat att ttt cat cct aca gat cca gtg 2199 Glu Ile Cys Asn Arg Leu Leu Asn Ile Phe His Pro Thr Asp Pro Val 655 660 665 gct tat aga tta gaa cca tta ata ctg aaa cac tac agc aac att tca 2247 Ala Tyr Arg Leu Glu Pro Leu Ile Leu Lys His Tyr Ser Asn Ile Ser 670 675 680 cct gtc cag atc cac tgg tac aat act tca aat cct tta cct tat gaa 2295 Pro Val Gln Ile His Trp Tyr Asn Thr Ser Asn Pro Leu Pro Tyr Glu 685 690 695 cat atg aag cca agc ttt ctc aac cca gct aaa gaa cct acc tca gtt 2343 His Met Lys Pro Ser Phe Leu Asn Pro Ala Lys Glu Pro Thr Ser Val 700 705 710 tca gag aat gaa ggc att tca acc ata cca agc cct gtg acc tca cca 2391 Ser Glu Asn Glu Gly Ile Ser Thr Ile Pro Ser Pro Val Thr Ser Pro 715 720 725 730 gtt ttg tcc cgc cga cac tat gga gaa tct ata aca aat ata ggc aaa 2439 Val Leu Ser Arg Arg His Tyr Gly Glu Ser Ile Thr Asn Ile Gly Lys 735 740 745 gca agc ata tta ggg gct gct agc att gga aag gga ctt gga gga atg 2487 Ala Ser Ile Leu Gly Ala Ala Ser Ile Gly Lys Gly Leu Gly Gly Met 750 755 760 ttg ttc tca aga ttt gga cgt tca tct aca aca cag tca tct gaa aca 2535 Leu Phe Ser Arg Phe Gly Arg Ser Ser Thr Thr Gln Ser Ser Glu Thr 765 770 775 tca aaa gac tca atg gaa gat gag aag aag cca gtt gcc tca cct tct 2583 Ser Lys Asp Ser Met Glu Asp Glu Lys Lys Pro Val Ala Ser Pro Ser 780 785 790 gct acc acc gta ggg aca cag acc ctt cca cat agc agt tct ggc ttc 2631 Ala Thr Thr Val Gly Thr Gln Thr Leu Pro His Ser Ser Ser Gly Phe 795 800 805 810 ctc gat tct gca ttg gag ttg gat cac agg att gat ttt gaa ctc aga 2679 Leu Asp Ser Ala Leu Glu Leu Asp His Arg Ile Asp Phe Glu Leu Arg 815 820 825 gaa ggc ctt gtg gag agc cgc tat tgg tca gct gtc acg tcg cat act 2727 Glu Gly Leu Val Glu Ser Arg Tyr Trp Ser Ala Val Thr Ser His Thr 830 835 840 gcc tat tgg tca tcc ttg gat gtt gcc ctt ttt ctt tta acc ttc atg 2775 Ala Tyr Trp Ser Ser Leu Asp Val Ala Leu Phe Leu Leu Thr Phe Met 845 850 855 tat aaa cat gag cac gat gat gat gca aaa ccc aat tta gat cca atc 2823 Tyr Lys His Glu His Asp Asp Asp Ala Lys Pro Asn Leu Asp Pro Ile 860 865 870 tga actcttgaag gacatgaatg gcctaaaact gatttttttt tttttccgtt 2876 * aaaatgtgtg tgtcaagata cggagatttc agggttaaag tatatttcag ttttctttag 2936 ggcaacatat atttgaattt aaaagcactt tatttaaaaa aaaaa 2981 2 874 PRT Homo sapiens 2 Met Asn Tyr Pro Gly Arg Gly Ser Pro Arg Ser Pro Glu His Asn Gly 1 5 10 15 Arg Gly Gly Gly Gly Gly Ala Trp Glu Leu Gly Ser Asp Ala Arg Pro 20 25 30 Ala Phe Gly Gly Gly Val Cys Cys Phe Glu His Leu Pro Gly Gly Asp 35 40 45 Pro Asp Asp Gly Asp Val Pro Leu Ala Leu Leu Arg Gly Glu Pro Gly 50 55 60 Leu His Leu Ala Pro Gly Thr Asp Asp His Asn His His Leu Ala Leu 65 70 75 80 Asp Pro Cys Leu Ser Asp Glu Asn Tyr Asp Phe Ser Ser Ala Glu Ser 85 90 95 Gly Ser Ser Leu Arg Tyr Tyr Ser Glu Gly Glu Ser Gly Gly Gly Gly 100 105 110 Gly Gly Ser Ser Leu Ser Leu His Pro Pro Gln Gln Pro Pro Leu Val 115 120 125 Pro Thr Asn Ser Gly Gly Gly Gly Ala Thr Gly Gly Ser Pro Gly Glu 130 135 140 Arg Lys Arg Thr Arg Leu Gly Gly Pro Ala Ala Arg His Arg Tyr Glu 145 150 155 160 Val Val Thr Glu Leu Gly Pro Glu Glu Val Arg Trp Phe Tyr Lys Glu 165 170 175 Asp Lys Lys Thr Trp Lys Pro Phe Ile Gly Tyr Asp Ser Leu Arg Ile 180 185 190 Glu Leu Ala Phe Arg Thr Leu Leu Gln Thr Thr Gly Ala Arg Pro Gln 195 200 205 Gly Gly Asp Arg Asp Gly Asp His Val Cys Ser Pro Thr Ser Pro Ala 210 215 220 Ser Ser Ser Gly Glu Asp Asp Asp Glu Asp Arg Ala Cys Gly Phe Cys 225 230 235 240 Gln Ser Thr Thr Gly His Glu Pro Glu Met Val Glu Leu Val Asn Ile 245 250 255 Glu Pro Val Cys Val Arg Gly Gly Leu Tyr Glu Val Asp Val Thr Gln 260 265 270 Gly Glu Cys Tyr Pro Val Tyr Trp Asn Gln Ala Asp Lys Ile Pro Val 275 280 285 Met Arg Gly Gln Trp Phe Ile Asp Gly Thr Trp Gln Pro Leu Glu Glu 290 295 300 Glu Glu Ser Asn Leu Ile Glu Gln Glu His Leu Asn Cys Phe Arg Gly 305 310 315 320 Gln Gln Met Gln Glu Asn Phe Asp Ile Glu Val Ser Lys Ser Ile Asp 325 330 335 Gly Lys Asp Ala Val His Ser Phe Lys Leu Ser Arg Asn His Val Asp 340 345 350 Trp His Ser Val Asp Glu Val Tyr Leu Tyr Ser Asp Ala Thr Thr Ser 355 360 365 Lys Ile Ala Arg Thr Val Thr Gln Lys Leu Gly Phe Ser Lys Ala Ser 370 375 380 Ser Ser Gly Thr Arg Leu His Arg Gly Tyr Val Glu Glu Ala Thr Leu 385 390 395 400 Glu Asp Lys Pro Ser Gln Thr Thr His Ile Val Phe Val Val His Gly 405 410 415 Ile Gly Gln Lys Met Asp Gln Gly Arg Ile Ile Lys Asn Thr Ala Met 420 425 430 Met Arg Glu Ala Ala Arg Lys Ile Glu Glu Arg His Phe Ser Asn His 435 440 445 Ala Thr His Val Glu Phe Leu Pro Val Glu Trp Arg Ser Lys Leu Thr 450 455 460 Leu Asp Gly Asp Thr Val Asp Ser Ile Thr Pro Asp Lys Val Arg Gly 465 470 475 480 Leu Arg Asp Met Leu Asn Ser Ser Ala Met Asp Ile Met Tyr Tyr Thr 485 490 495 Ser Pro Leu Tyr Arg Asp Glu Leu Val Lys Gly Leu Gln Gln Glu Leu 500 505 510 Asn Arg Leu Tyr Ser Leu Phe Cys Ser Arg Asn Pro Asp Phe Glu Glu 515 520 525 Lys Gly Gly Lys Val Ser Ile Val Ser His Ser Leu Gly Cys Val Ile 530 535 540 Thr Tyr Asp Ile Met Thr Gly Trp Asn Pro Val Arg Leu Tyr Glu Gln 545 550 555 560 Leu Leu Gln Lys Glu Glu Glu Leu Pro Asp Glu Arg Trp Met Ser Tyr 565 570 575 Glu Glu Arg His Leu Leu Asp Glu Leu Tyr Ile Thr Lys Arg Arg Leu 580 585 590 Lys Glu Ile Glu Glu Arg Leu His Gly Leu Lys Ala Ser Ser Met Thr 595 600 605 Gln Thr Pro Ala Leu Lys Phe Lys Val Glu Asn Phe Phe Cys Met Gly 610 615 620 Ser Pro Leu Ala Val Phe Leu Ala Leu Arg Gly Ile Arg Pro Gly Asn 625 630 635 640 Thr Gly Ser Gln Asp His Ile Leu Pro Arg Glu Ile Cys Asn Arg Leu 645 650 655 Leu Asn Ile Phe His Pro Thr Asp Pro Val Ala Tyr Arg Leu Glu Pro 660 665 670 Leu Ile Leu Lys His Tyr Ser Asn Ile Ser Pro Val Gln Ile His Trp 675 680 685 Tyr Asn Thr Ser Asn Pro Leu Pro Tyr Glu His Met Lys Pro Ser Phe 690 695 700 Leu Asn Pro Ala Lys Glu Pro Thr Ser Val Ser Glu Asn Glu Gly Ile 705 710 715 720 Ser Thr Ile Pro Ser Pro Val Thr Ser Pro Val Leu Ser Arg Arg His 725 730 735 Tyr Gly Glu Ser Ile Thr Asn Ile Gly Lys Ala Ser Ile Leu Gly Ala 740 745 750 Ala Ser Ile Gly Lys Gly Leu Gly Gly Met Leu Phe Ser Arg Phe Gly 755 760 765 Arg Ser Ser Thr Thr Gln Ser Ser Glu Thr Ser Lys Asp Ser Met Glu 770 775 780 Asp Glu Lys Lys Pro Val Ala Ser Pro Ser Ala Thr Thr Val Gly Thr 785 790 795 800 Gln Thr Leu Pro His Ser Ser Ser Gly Phe Leu Asp Ser Ala Leu Glu 805 810 815 Leu Asp His Arg Ile Asp Phe Glu Leu Arg Glu Gly Leu Val Glu Ser 820 825 830 Arg Tyr Trp Ser Ala Val Thr Ser His Thr Ala Tyr Trp Ser Ser Leu 835 840 845 Asp Val Ala Leu Phe Leu Leu Thr Phe Met Tyr Lys His Glu His Asp 850 855 860 Asp Asp Ala Lys Pro Asn Leu Asp Pro Ile 865 870 3 2622 DNA Homo sapiens CDS (1)...(2622) 3 atg aat tac ccg ggc cgc ggg tcc cca cgg agc ccc gag cat aac ggc 48 Met Asn Tyr Pro Gly Arg Gly Ser Pro Arg Ser Pro Glu His Asn Gly 1 5 10 15 cga ggc ggc ggc ggc ggc gcc tgg gag ctg ggc tca gac gcg agg cca 96 Arg Gly Gly Gly Gly Gly Ala Trp Glu Leu Gly Ser Asp Ala Arg Pro 20 25 30 gcg ttc ggc ggc ggc gtc tgc tgc ttc gag cac ctg ccc ggc ggg gac 144 Ala Phe Gly Gly Gly Val Cys Cys Phe Glu His Leu Pro Gly Gly Asp 35 40 45 ccg gac gac ggc gac gtg ccc ctg gcc ctg ctg cgc ggg gaa ccc

ggg 192 Pro Asp Asp Gly Asp Val Pro Leu Ala Leu Leu Arg Gly Glu Pro Gly 50 55 60 ctg cat ttg gcg ccg ggc acc gac gac cac aac cac cac ctc gcg ctg 240 Leu His Leu Ala Pro Gly Thr Asp Asp His Asn His His Leu Ala Leu 65 70 75 80 gac ccc tgc ctc agt gac gag aac tat gac ttt agc tcc gcc gag tcg 288 Asp Pro Cys Leu Ser Asp Glu Asn Tyr Asp Phe Ser Ser Ala Glu Ser 85 90 95 ggc tcc tcg ctg cgc tac tac agc gag ggt gag agc ggc ggc ggc ggc 336 Gly Ser Ser Leu Arg Tyr Tyr Ser Glu Gly Glu Ser Gly Gly Gly Gly 100 105 110 ggc ggc agc tcc ttg tcg ctg cat ccg ccg cag cag cct ccg ctg gtc 384 Gly Gly Ser Ser Leu Ser Leu His Pro Pro Gln Gln Pro Pro Leu Val 115 120 125 ccg acg aac tcg ggg ggc ggc ggc gcg aca gga ggg tcc ccc ggg gaa 432 Pro Thr Asn Ser Gly Gly Gly Gly Ala Thr Gly Gly Ser Pro Gly Glu 130 135 140 agg aaa cgt acc cgg ctt ggc ggc ccg gcg gcc cgg cac cgc tat gag 480 Arg Lys Arg Thr Arg Leu Gly Gly Pro Ala Ala Arg His Arg Tyr Glu 145 150 155 160 gta gtg acg gag ctg ggc ccg gag gag gta cgc tgg ttc tac aag gag 528 Val Val Thr Glu Leu Gly Pro Glu Glu Val Arg Trp Phe Tyr Lys Glu 165 170 175 gac aag aag acc tgg aag ccc ttc atc ggc tac gac tcg ctc cgc atc 576 Asp Lys Lys Thr Trp Lys Pro Phe Ile Gly Tyr Asp Ser Leu Arg Ile 180 185 190 gag ctc gcc ttc cgg acc ctg ctg cag acc acg ggt gcc cgg ccc cag 624 Glu Leu Ala Phe Arg Thr Leu Leu Gln Thr Thr Gly Ala Arg Pro Gln 195 200 205 ggc ggg gac cgg gac ggc gac cat gtg tgc tcc ccc acg agc cca gcc 672 Gly Gly Asp Arg Asp Gly Asp His Val Cys Ser Pro Thr Ser Pro Ala 210 215 220 tcc agt tcc gga gaa gat gac gat gag gac cgc gcc tgc ggc ttc tgc 720 Ser Ser Ser Gly Glu Asp Asp Asp Glu Asp Arg Ala Cys Gly Phe Cys 225 230 235 240 cag agt acg acg ggg cac gag ccg gag atg gtg gag ctt gtg aac atc 768 Gln Ser Thr Thr Gly His Glu Pro Glu Met Val Glu Leu Val Asn Ile 245 250 255 gag cct gtg tgc gtg cgg ggc ggc ctc tac gag gtg gat gtg acc caa 816 Glu Pro Val Cys Val Arg Gly Gly Leu Tyr Glu Val Asp Val Thr Gln 260 265 270 gga gag tgc tac ccg gtg tac tgg aac cag gct gat aaa ata cca gta 864 Gly Glu Cys Tyr Pro Val Tyr Trp Asn Gln Ala Asp Lys Ile Pro Val 275 280 285 atg cgt gga cag tgg ttt att gac ggc act tgg cag cct cta gaa gag 912 Met Arg Gly Gln Trp Phe Ile Asp Gly Thr Trp Gln Pro Leu Glu Glu 290 295 300 gaa gaa agt aat tta att gag caa gaa cat ctc aat tgt ttt agg ggc 960 Glu Glu Ser Asn Leu Ile Glu Gln Glu His Leu Asn Cys Phe Arg Gly 305 310 315 320 cag cag atg cag gaa aat ttc gat att gaa gtg tca aaa tcc ata gat 1008 Gln Gln Met Gln Glu Asn Phe Asp Ile Glu Val Ser Lys Ser Ile Asp 325 330 335 gga aaa gat gct gtt cat agt ttc aag ttg agt cga aac cat gtg gac 1056 Gly Lys Asp Ala Val His Ser Phe Lys Leu Ser Arg Asn His Val Asp 340 345 350 tgg cac agt gtg gat gaa gta tat ctt tat agt gat gca aca aca tct 1104 Trp His Ser Val Asp Glu Val Tyr Leu Tyr Ser Asp Ala Thr Thr Ser 355 360 365 aaa att gca aga aca gtt acc caa aaa ctg gga ttt tct aaa gca tca 1152 Lys Ile Ala Arg Thr Val Thr Gln Lys Leu Gly Phe Ser Lys Ala Ser 370 375 380 agt agt ggt acc aga ctt cat aga ggt tat gta gaa gaa gcc aca tta 1200 Ser Ser Gly Thr Arg Leu His Arg Gly Tyr Val Glu Glu Ala Thr Leu 385 390 395 400 gaa gac aag cca tca cag act acc cat att gta ttt gtt gtg cat ggc 1248 Glu Asp Lys Pro Ser Gln Thr Thr His Ile Val Phe Val Val His Gly 405 410 415 att ggg cag aaa atg gac caa gga aga att atc aaa aat aca gct atg 1296 Ile Gly Gln Lys Met Asp Gln Gly Arg Ile Ile Lys Asn Thr Ala Met 420 425 430 atg aga gaa gct gca aga aaa ata gaa gaa agg cat ttt tcc aac cat 1344 Met Arg Glu Ala Ala Arg Lys Ile Glu Glu Arg His Phe Ser Asn His 435 440 445 gca aca cat gtt gaa ttt ctg cct gtt gag tgg cgg tca aaa ctt act 1392 Ala Thr His Val Glu Phe Leu Pro Val Glu Trp Arg Ser Lys Leu Thr 450 455 460 ctt gat gga gac act gtt gat tcc att act cct gac aaa gta cga ggt 1440 Leu Asp Gly Asp Thr Val Asp Ser Ile Thr Pro Asp Lys Val Arg Gly 465 470 475 480 tta agg gat atg ctg aac agc agt gca atg gac ata atg tat tat act 1488 Leu Arg Asp Met Leu Asn Ser Ser Ala Met Asp Ile Met Tyr Tyr Thr 485 490 495 agt cca ctt tat aga gat gaa cta gtt aaa ggc ctt cag caa gag ctg 1536 Ser Pro Leu Tyr Arg Asp Glu Leu Val Lys Gly Leu Gln Gln Glu Leu 500 505 510 aat cga ttg tat tcc ctt ttc tgt tct cgg aat cca gac ttt gaa gaa 1584 Asn Arg Leu Tyr Ser Leu Phe Cys Ser Arg Asn Pro Asp Phe Glu Glu 515 520 525 aaa ggg ggt aaa gtc tca ata gta tca cat tcc ttg gga tgt gta att 1632 Lys Gly Gly Lys Val Ser Ile Val Ser His Ser Leu Gly Cys Val Ile 530 535 540 act tat gac ata atg act ggc tgg aat cca gtt cgg ctg tat gaa cag 1680 Thr Tyr Asp Ile Met Thr Gly Trp Asn Pro Val Arg Leu Tyr Glu Gln 545 550 555 560 ttg ctg caa aag gaa gaa gag ttg cct gat gaa cga tgg atg agc tat 1728 Leu Leu Gln Lys Glu Glu Glu Leu Pro Asp Glu Arg Trp Met Ser Tyr 565 570 575 gaa gaa cga cat ctt ctt gat gaa ctc tat ata aca aaa cga cgg ctg 1776 Glu Glu Arg His Leu Leu Asp Glu Leu Tyr Ile Thr Lys Arg Arg Leu 580 585 590 aag gaa ata gaa gaa cgg ctt cac gga ttg aaa gca tca tct atg aca 1824 Lys Glu Ile Glu Glu Arg Leu His Gly Leu Lys Ala Ser Ser Met Thr 595 600 605 caa aca cct gcc tta aaa ttt aag gtt gag aat ttc ttc tgt atg gga 1872 Gln Thr Pro Ala Leu Lys Phe Lys Val Glu Asn Phe Phe Cys Met Gly 610 615 620 tcc cca tta gca gtt ttc ttg gcg ttg cgt ggc atc cgc cca gga aat 1920 Ser Pro Leu Ala Val Phe Leu Ala Leu Arg Gly Ile Arg Pro Gly Asn 625 630 635 640 act gga agt caa gac cat att ttg cct aga gag att tgt aac cgg tta 1968 Thr Gly Ser Gln Asp His Ile Leu Pro Arg Glu Ile Cys Asn Arg Leu 645 650 655 cta aat att ttt cat cct aca gat cca gtg gct tat aga tta gaa cca 2016 Leu Asn Ile Phe His Pro Thr Asp Pro Val Ala Tyr Arg Leu Glu Pro 660 665 670 tta ata ctg aaa cac tac agc aac att tca cct gtc cag atc cac tgg 2064 Leu Ile Leu Lys His Tyr Ser Asn Ile Ser Pro Val Gln Ile His Trp 675 680 685 tac aat act tca aat cct tta cct tat gaa cat atg aag cca agc ttt 2112 Tyr Asn Thr Ser Asn Pro Leu Pro Tyr Glu His Met Lys Pro Ser Phe 690 695 700 ctc aac cca gct aaa gaa cct acc tca gtt tca gag aat gaa ggc att 2160 Leu Asn Pro Ala Lys Glu Pro Thr Ser Val Ser Glu Asn Glu Gly Ile 705 710 715 720 tca acc ata cca agc cct gtg acc tca cca gtt ttg tcc cgc cga cac 2208 Ser Thr Ile Pro Ser Pro Val Thr Ser Pro Val Leu Ser Arg Arg His 725 730 735 tat gga gaa tct ata aca aat ata ggc aaa gca agc ata tta ggg gct 2256 Tyr Gly Glu Ser Ile Thr Asn Ile Gly Lys Ala Ser Ile Leu Gly Ala 740 745 750 gct agc att gga aag gga ctt gga gga atg ttg ttc tca aga ttt gga 2304 Ala Ser Ile Gly Lys Gly Leu Gly Gly Met Leu Phe Ser Arg Phe Gly 755 760 765 cgt tca tct aca aca cag tca tct gaa aca tca aaa gac tca atg gaa 2352 Arg Ser Ser Thr Thr Gln Ser Ser Glu Thr Ser Lys Asp Ser Met Glu 770 775 780 gat gag aag aag cca gtt gcc tca cct tct gct acc acc gta ggg aca 2400 Asp Glu Lys Lys Pro Val Ala Ser Pro Ser Ala Thr Thr Val Gly Thr 785 790 795 800 cag acc ctt cca cat agc agt tct ggc ttc ctc gat tct gca ttg gag 2448 Gln Thr Leu Pro His Ser Ser Ser Gly Phe Leu Asp Ser Ala Leu Glu 805 810 815 ttg gat cac agg att gat ttt gaa ctc aga gaa ggc ctt gtg gag agc 2496 Leu Asp His Arg Ile Asp Phe Glu Leu Arg Glu Gly Leu Val Glu Ser 820 825 830 cgc tat tgg tca gct gtc acg tcg cat act gcc tat tgg tca tcc ttg 2544 Arg Tyr Trp Ser Ala Val Thr Ser His Thr Ala Tyr Trp Ser Ser Leu 835 840 845 gat gtt gcc ctt ttt ctt tta acc ttc atg tat aaa cat gag cac gat 2592 Asp Val Ala Leu Phe Leu Leu Thr Phe Met Tyr Lys His Glu His Asp 850 855 860 gat gat gca aaa ccc aat tta gat cca atc 2622 Asp Asp Ala Lys Pro Asn Leu Asp Pro Ile 865 870 4 3065 DNA Homo sapiens CDS (202)...(2910) 4 cacgaggccg gcggcagaac gcagctgcgg cggctgcggg tctcgtgggg gcggagcggt 60 cgccgctgcc gccgcagctc gggtcgggat ttgaaagatt agaaacttcg ggtggagagg 120 gcggcggcgt tgaatgtgtg gcggaagcgc tgggggtcac ggctccgcgc gccgccggac 180 agccggcggc gtctccacag c atg aat tac ccg ggc cgc ggg tcc cca cgg 231 Met Asn Tyr Pro Gly Arg Gly Ser Pro Arg 1 5 10 agc ccc gag cat aac ggc cga ggc ggc ggc ggc ggc gcc tgg gag ctg 279 Ser Pro Glu His Asn Gly Arg Gly Gly Gly Gly Gly Ala Trp Glu Leu 15 20 25 ggc tca gac gcg agg cca gcg ttc ggc ggc ggc gtc tgc tgc ttc gag 327 Gly Ser Asp Ala Arg Pro Ala Phe Gly Gly Gly Val Cys Cys Phe Glu 30 35 40 cac ctg ccc ggc ggg gac ccg gac gac ggc gac gtg ccc ctg gcc ctg 375 His Leu Pro Gly Gly Asp Pro Asp Asp Gly Asp Val Pro Leu Ala Leu 45 50 55 ctg cgc ggg gaa ccc ggg ctg cat ttg gcg ccg ggc acc gac gac cac 423 Leu Arg Gly Glu Pro Gly Leu His Leu Ala Pro Gly Thr Asp Asp His 60 65 70 aac cac cac ctc gcg ctg gac ccc tgc ctc agt gac gag aac tat gac 471 Asn His His Leu Ala Leu Asp Pro Cys Leu Ser Asp Glu Asn Tyr Asp 75 80 85 90 ttt agc tcc gcc gag tcg ggc tcc tcg ctg cgc tac tac agc gag ggt 519 Phe Ser Ser Ala Glu Ser Gly Ser Ser Leu Arg Tyr Tyr Ser Glu Gly 95 100 105 gag agc ggc ggc ggc ggc ggc ggc agc tcc ttg tcg ctg cat ccg ccg 567 Glu Ser Gly Gly Gly Gly Gly Gly Ser Ser Leu Ser Leu His Pro Pro 110 115 120 cag cag cct ccg ctg gtc ccg acg aac tcg ggg ggc ggc ggc gcg aca 615 Gln Gln Pro Pro Leu Val Pro Thr Asn Ser Gly Gly Gly Gly Ala Thr 125 130 135 gga ggg tcc ccc ggg gaa agg aaa cgt acc cgg ctt ggc ggc ccg gcg 663 Gly Gly Ser Pro Gly Glu Arg Lys Arg Thr Arg Leu Gly Gly Pro Ala 140 145 150 gcc cgg cac cgc tat gag gta gtg acg gag ctg ggc ccg gag gag gta 711 Ala Arg His Arg Tyr Glu Val Val Thr Glu Leu Gly Pro Glu Glu Val 155 160 165 170 cgc tgg ttc tac aag gag gac aag aag acc tgg aag ccc ttc atc ggc 759 Arg Trp Phe Tyr Lys Glu Asp Lys Lys Thr Trp Lys Pro Phe Ile Gly 175 180 185 tac gac tcg ctc cgc atc gag ctc gcc ttc cgg acc ctg ctg cag acc 807 Tyr Asp Ser Leu Arg Ile Glu Leu Ala Phe Arg Thr Leu Leu Gln Thr 190 195 200 acg ggt gcc cgg ccc cag ggc ggg gac cgg gac ggc gac cat gtg tgc 855 Thr Gly Ala Arg Pro Gln Gly Gly Asp Arg Asp Gly Asp His Val Cys 205 210 215 tcc ccc acg agc cca gcc tcc agt tcc gga gaa gat gac gat gag gac 903 Ser Pro Thr Ser Pro Ala Ser Ser Ser Gly Glu Asp Asp Asp Glu Asp 220 225 230 cgc gcc tgc ggc ttc tgc cag agt acg acg ggg cac gag ccg gag atg 951 Arg Ala Cys Gly Phe Cys Gln Ser Thr Thr Gly His Glu Pro Glu Met 235 240 245 250 gtg gag ctt gtg aac atc gag cct gtg tgc gtg cgg ggc ggc ctc tac 999 Val Glu Leu Val Asn Ile Glu Pro Val Cys Val Arg Gly Gly Leu Tyr 255 260 265 gag gtg gat gtg acc caa gga gag tgc tac ccg gtg tac tgg aac cag 1047 Glu Val Asp Val Thr Gln Gly Glu Cys Tyr Pro Val Tyr Trp Asn Gln 270 275 280 gct gat aaa ata cca gta atg cgt gga cag tgg ttt att gac ggc act 1095 Ala Asp Lys Ile Pro Val Met Arg Gly Gln Trp Phe Ile Asp Gly Thr 285 290 295 tgg cag cct cta gaa gag gaa gaa agt aat tta att gag caa gaa cat 1143 Trp Gln Pro Leu Glu Glu Glu Glu Ser Asn Leu Ile Glu Gln Glu His 300 305 310 ctc aat tgt ttt agg ggc cag cag atg cag gaa aat ttc gat att gaa 1191 Leu Asn Cys Phe Arg Gly Gln Gln Met Gln Glu Asn Phe Asp Ile Glu 315 320 325 330 gtg tca aaa tcc ata gat gga aaa gat gct gtt cat agt ttc aag ttg 1239 Val Ser Lys Ser Ile Asp Gly Lys Asp Ala Val His Ser Phe Lys Leu 335 340 345 agt cga aac cat gtg gac tgg cac agt gtg gat gaa gta tat ctt tat 1287 Ser Arg Asn His Val Asp Trp His Ser Val Asp Glu Val Tyr Leu Tyr 350 355 360 agt gat gca aca aca tct aaa att gca aga aca gtt acc caa aaa ctg 1335 Ser Asp Ala Thr Thr Ser Lys Ile Ala Arg Thr Val Thr Gln Lys Leu 365 370 375 gga ttt tct aaa gca tca agt agt ggt acc aga ctt cat aga ggt tat 1383 Gly Phe Ser Lys Ala Ser Ser Ser Gly Thr Arg Leu His Arg Gly Tyr 380 385 390 gta gaa gaa gcc aca tta gaa gac aag cca tca cag act acc cat att 1431 Val Glu Glu Ala Thr Leu Glu Asp Lys Pro Ser Gln Thr Thr His Ile 395 400 405 410 gta ttt gtt gtg cat ggc att ggg cag aaa atg gac caa gga aga att 1479 Val Phe Val Val His Gly Ile Gly Gln Lys Met Asp Gln Gly Arg Ile 415 420 425 atc aaa aat aca gct atg atg aga gaa gct gca aga aaa ata gaa gaa 1527 Ile Lys Asn Thr Ala Met Met Arg Glu Ala Ala Arg Lys Ile Glu Glu 430 435 440 agg cat ttt tcc aac cat gca aca cat gtt gaa ttt ctg cct gtt gag 1575 Arg His Phe Ser Asn His Ala Thr His Val Glu Phe Leu Pro Val Glu 445 450 455 tgg cgg tca aaa ctt act ctt gat gga gac act gtt gat tcc att act 1623 Trp Arg Ser Lys Leu Thr Leu Asp Gly Asp Thr Val Asp Ser Ile Thr 460 465 470 cct gac aaa gta cga ggt tta agg gat atg ctg aac agc agt gca atg 1671 Pro Asp Lys Val Arg Gly Leu Arg Asp Met Leu Asn Ser Ser Ala Met 475 480 485 490 gac ata atg tat tat act agt cca ctt tat aga gat gaa cta gtt aaa 1719 Asp Ile Met Tyr Tyr Thr Ser Pro Leu Tyr Arg Asp Glu Leu Val Lys 495 500 505 ggc ctt cag caa gag ctg aat cga ttg tat tcc ctt ttc tgt tct cgg 1767 Gly Leu Gln Gln Glu Leu Asn Arg Leu Tyr Ser Leu Phe Cys Ser Arg 510 515 520 aat cca gac ttt gaa gaa aaa ggg ggt aaa gtc tca ata gta tca cat 1815 Asn Pro Asp Phe Glu Glu Lys Gly Gly Lys Val Ser Ile Val Ser His 525 530 535 tcc ttg gga tgt gta att act tat gac ata atg act ggc tgg aat cca 1863 Ser Leu Gly Cys Val Ile Thr Tyr Asp Ile Met Thr Gly Trp Asn Pro 540 545 550 gtt cgg ctg tat gaa cag ttg ctg caa aag gaa gaa gag ttg cct gat 1911 Val Arg Leu Tyr Glu Gln Leu Leu Gln Lys Glu Glu Glu Leu Pro Asp 555 560 565 570 gaa cga tgg atg agc tat gaa gaa cga cat ctt ctt gat gaa ctc tat 1959 Glu Arg Trp Met Ser Tyr Glu Glu Arg His Leu Leu Asp Glu Leu Tyr 575 580 585 ata aca aaa cga cgg ctg aag gaa ata gaa gaa cgg ctt cac gga ttg 2007 Ile Thr Lys Arg Arg Leu Lys Glu Ile Glu Glu Arg Leu His Gly Leu 590 595 600 aaa gca tca tct atg aca caa aca cct gcc tta aaa ttt aag gtt gag 2055 Lys Ala Ser Ser Met Thr Gln Thr Pro Ala Leu Lys Phe Lys Val Glu 605 610 615 aat ttc ttc tgt atg gga tcc cca tta gca gtt ttc ttg gcg ttg cgt 2103 Asn Phe Phe Cys Met Gly Ser Pro Leu Ala Val Phe Leu Ala Leu Arg 620 625 630 ggc atc cgc cca gga aat act gga agt caa gac cat att ttg cct aga 2151 Gly Ile Arg Pro Gly Asn Thr Gly Ser Gln Asp His Ile Leu Pro Arg 635 640 645 650 gag att tgt aac cgg tta cta aat att ttt cat cct aca gat cca gtg 2199 Glu Ile Cys Asn Arg Leu Leu Asn Ile Phe His Pro Thr Asp Pro Val 655 660 665 gct tat aga tta gaa cca tta ata ctg aaa cac tac agc aac att tca

2247 Ala Tyr Arg Leu Glu Pro Leu Ile Leu Lys His Tyr Ser Asn Ile Ser 670 675 680 cct gtc cag atc cac tgg tac aat act tca aat cct tta cct tat gaa 2295 Pro Val Gln Ile His Trp Tyr Asn Thr Ser Asn Pro Leu Pro Tyr Glu 685 690 695 cat atg aag cca agc ttt ctc aac cca gct aaa gaa cct acc tca gtt 2343 His Met Lys Pro Ser Phe Leu Asn Pro Ala Lys Glu Pro Thr Ser Val 700 705 710 tca gag aat gaa ggc att tca acc ata cca agc cct gtg acc tca cca 2391 Ser Glu Asn Glu Gly Ile Ser Thr Ile Pro Ser Pro Val Thr Ser Pro 715 720 725 730 gtt ttg tcc cgc cga cac tat gga gaa tct ata aca aat ata ggc aaa 2439 Val Leu Ser Arg Arg His Tyr Gly Glu Ser Ile Thr Asn Ile Gly Lys 735 740 745 gca agc ata tta ggg gct gct agc att gga aag gga ctt gga gga atg 2487 Ala Ser Ile Leu Gly Ala Ala Ser Ile Gly Lys Gly Leu Gly Gly Met 750 755 760 ttg ttc tca aga ttt gga cgt tca tct aca aca cag tca tct gaa aca 2535 Leu Phe Ser Arg Phe Gly Arg Ser Ser Thr Thr Gln Ser Ser Glu Thr 765 770 775 tca aaa gac tca atg gaa gat gag aag aag cca gtt gcc tca cct tct 2583 Ser Lys Asp Ser Met Glu Asp Glu Lys Lys Pro Val Ala Ser Pro Ser 780 785 790 gct acc acc gta ggg aca cag acc ctt cca cat agc agt tct ggc ttc 2631 Ala Thr Thr Val Gly Thr Gln Thr Leu Pro His Ser Ser Ser Gly Phe 795 800 805 810 ctc gat tct gca tat ttc aga ctt caa gaa tcg ttc ttt aat ctc cca 2679 Leu Asp Ser Ala Tyr Phe Arg Leu Gln Glu Ser Phe Phe Asn Leu Pro 815 820 825 caa ctt ctt ttt ccg gaa aat gta atg cag aat aaa gat aat gcc ctc 2727 Gln Leu Leu Phe Pro Glu Asn Val Met Gln Asn Lys Asp Asn Ala Leu 830 835 840 gtg gag ttg gat cac agg att gat ttt gaa ctc aga gaa ggc ctt gtg 2775 Val Glu Leu Asp His Arg Ile Asp Phe Glu Leu Arg Glu Gly Leu Val 845 850 855 gag agc cgc tat tgg tca gct gtc acg tcg cat act gcc tat tgg tca 2823 Glu Ser Arg Tyr Trp Ser Ala Val Thr Ser His Thr Ala Tyr Trp Ser 860 865 870 tcc ttg gat gtt gcc ctt ttt ctt tta acc ttc atg tat aaa cat gag 2871 Ser Leu Asp Val Ala Leu Phe Leu Leu Thr Phe Met Tyr Lys His Glu 875 880 885 890 cac gat gat gat gca aaa ccc aat tta gat cca atc tga actcttgaag 2920 His Asp Asp Asp Ala Lys Pro Asn Leu Asp Pro Ile * 895 900 gacatgaatg gcctaaaact gatttttttt tttttccgtt aaaatgtgtg tgtcaagata 2980 cggagatttc agggttaaag tatatttcag ttttctttag ggcaacatat atttgaattt 3040 aaaagcactt tatttaaaaa aaaaa 3065 5 902 PRT Homo sapiens 5 Met Asn Tyr Pro Gly Arg Gly Ser Pro Arg Ser Pro Glu His Asn Gly 1 5 10 15 Arg Gly Gly Gly Gly Gly Ala Trp Glu Leu Gly Ser Asp Ala Arg Pro 20 25 30 Ala Phe Gly Gly Gly Val Cys Cys Phe Glu His Leu Pro Gly Gly Asp 35 40 45 Pro Asp Asp Gly Asp Val Pro Leu Ala Leu Leu Arg Gly Glu Pro Gly 50 55 60 Leu His Leu Ala Pro Gly Thr Asp Asp His Asn His His Leu Ala Leu 65 70 75 80 Asp Pro Cys Leu Ser Asp Glu Asn Tyr Asp Phe Ser Ser Ala Glu Ser 85 90 95 Gly Ser Ser Leu Arg Tyr Tyr Ser Glu Gly Glu Ser Gly Gly Gly Gly 100 105 110 Gly Gly Ser Ser Leu Ser Leu His Pro Pro Gln Gln Pro Pro Leu Val 115 120 125 Pro Thr Asn Ser Gly Gly Gly Gly Ala Thr Gly Gly Ser Pro Gly Glu 130 135 140 Arg Lys Arg Thr Arg Leu Gly Gly Pro Ala Ala Arg His Arg Tyr Glu 145 150 155 160 Val Val Thr Glu Leu Gly Pro Glu Glu Val Arg Trp Phe Tyr Lys Glu 165 170 175 Asp Lys Lys Thr Trp Lys Pro Phe Ile Gly Tyr Asp Ser Leu Arg Ile 180 185 190 Glu Leu Ala Phe Arg Thr Leu Leu Gln Thr Thr Gly Ala Arg Pro Gln 195 200 205 Gly Gly Asp Arg Asp Gly Asp His Val Cys Ser Pro Thr Ser Pro Ala 210 215 220 Ser Ser Ser Gly Glu Asp Asp Asp Glu Asp Arg Ala Cys Gly Phe Cys 225 230 235 240 Gln Ser Thr Thr Gly His Glu Pro Glu Met Val Glu Leu Val Asn Ile 245 250 255 Glu Pro Val Cys Val Arg Gly Gly Leu Tyr Glu Val Asp Val Thr Gln 260 265 270 Gly Glu Cys Tyr Pro Val Tyr Trp Asn Gln Ala Asp Lys Ile Pro Val 275 280 285 Met Arg Gly Gln Trp Phe Ile Asp Gly Thr Trp Gln Pro Leu Glu Glu 290 295 300 Glu Glu Ser Asn Leu Ile Glu Gln Glu His Leu Asn Cys Phe Arg Gly 305 310 315 320 Gln Gln Met Gln Glu Asn Phe Asp Ile Glu Val Ser Lys Ser Ile Asp 325 330 335 Gly Lys Asp Ala Val His Ser Phe Lys Leu Ser Arg Asn His Val Asp 340 345 350 Trp His Ser Val Asp Glu Val Tyr Leu Tyr Ser Asp Ala Thr Thr Ser 355 360 365 Lys Ile Ala Arg Thr Val Thr Gln Lys Leu Gly Phe Ser Lys Ala Ser 370 375 380 Ser Ser Gly Thr Arg Leu His Arg Gly Tyr Val Glu Glu Ala Thr Leu 385 390 395 400 Glu Asp Lys Pro Ser Gln Thr Thr His Ile Val Phe Val Val His Gly 405 410 415 Ile Gly Gln Lys Met Asp Gln Gly Arg Ile Ile Lys Asn Thr Ala Met 420 425 430 Met Arg Glu Ala Ala Arg Lys Ile Glu Glu Arg His Phe Ser Asn His 435 440 445 Ala Thr His Val Glu Phe Leu Pro Val Glu Trp Arg Ser Lys Leu Thr 450 455 460 Leu Asp Gly Asp Thr Val Asp Ser Ile Thr Pro Asp Lys Val Arg Gly 465 470 475 480 Leu Arg Asp Met Leu Asn Ser Ser Ala Met Asp Ile Met Tyr Tyr Thr 485 490 495 Ser Pro Leu Tyr Arg Asp Glu Leu Val Lys Gly Leu Gln Gln Glu Leu 500 505 510 Asn Arg Leu Tyr Ser Leu Phe Cys Ser Arg Asn Pro Asp Phe Glu Glu 515 520 525 Lys Gly Gly Lys Val Ser Ile Val Ser His Ser Leu Gly Cys Val Ile 530 535 540 Thr Tyr Asp Ile Met Thr Gly Trp Asn Pro Val Arg Leu Tyr Glu Gln 545 550 555 560 Leu Leu Gln Lys Glu Glu Glu Leu Pro Asp Glu Arg Trp Met Ser Tyr 565 570 575 Glu Glu Arg His Leu Leu Asp Glu Leu Tyr Ile Thr Lys Arg Arg Leu 580 585 590 Lys Glu Ile Glu Glu Arg Leu His Gly Leu Lys Ala Ser Ser Met Thr 595 600 605 Gln Thr Pro Ala Leu Lys Phe Lys Val Glu Asn Phe Phe Cys Met Gly 610 615 620 Ser Pro Leu Ala Val Phe Leu Ala Leu Arg Gly Ile Arg Pro Gly Asn 625 630 635 640 Thr Gly Ser Gln Asp His Ile Leu Pro Arg Glu Ile Cys Asn Arg Leu 645 650 655 Leu Asn Ile Phe His Pro Thr Asp Pro Val Ala Tyr Arg Leu Glu Pro 660 665 670 Leu Ile Leu Lys His Tyr Ser Asn Ile Ser Pro Val Gln Ile His Trp 675 680 685 Tyr Asn Thr Ser Asn Pro Leu Pro Tyr Glu His Met Lys Pro Ser Phe 690 695 700 Leu Asn Pro Ala Lys Glu Pro Thr Ser Val Ser Glu Asn Glu Gly Ile 705 710 715 720 Ser Thr Ile Pro Ser Pro Val Thr Ser Pro Val Leu Ser Arg Arg His 725 730 735 Tyr Gly Glu Ser Ile Thr Asn Ile Gly Lys Ala Ser Ile Leu Gly Ala 740 745 750 Ala Ser Ile Gly Lys Gly Leu Gly Gly Met Leu Phe Ser Arg Phe Gly 755 760 765 Arg Ser Ser Thr Thr Gln Ser Ser Glu Thr Ser Lys Asp Ser Met Glu 770 775 780 Asp Glu Lys Lys Pro Val Ala Ser Pro Ser Ala Thr Thr Val Gly Thr 785 790 795 800 Gln Thr Leu Pro His Ser Ser Ser Gly Phe Leu Asp Ser Ala Tyr Phe 805 810 815 Arg Leu Gln Glu Ser Phe Phe Asn Leu Pro Gln Leu Leu Phe Pro Glu 820 825 830 Asn Val Met Gln Asn Lys Asp Asn Ala Leu Val Glu Leu Asp His Arg 835 840 845 Ile Asp Phe Glu Leu Arg Glu Gly Leu Val Glu Ser Arg Tyr Trp Ser 850 855 860 Ala Val Thr Ser His Thr Ala Tyr Trp Ser Ser Leu Asp Val Ala Leu 865 870 875 880 Phe Leu Leu Thr Phe Met Tyr Lys His Glu His Asp Asp Asp Ala Lys 885 890 895 Pro Asn Leu Asp Pro Ile 900 6 2706 DNA Homo sapiens CDS (1)...(2706) 6 atg aat tac ccg ggc cgc ggg tcc cca cgg agc ccc gag cat aac ggc 48 Met Asn Tyr Pro Gly Arg Gly Ser Pro Arg Ser Pro Glu His Asn Gly 1 5 10 15 cga ggc ggc ggc ggc ggc gcc tgg gag ctg ggc tca gac gcg agg cca 96 Arg Gly Gly Gly Gly Gly Ala Trp Glu Leu Gly Ser Asp Ala Arg Pro 20 25 30 gcg ttc ggc ggc ggc gtc tgc tgc ttc gag cac ctg ccc ggc ggg gac 144 Ala Phe Gly Gly Gly Val Cys Cys Phe Glu His Leu Pro Gly Gly Asp 35 40 45 ccg gac gac ggc gac gtg ccc ctg gcc ctg ctg cgc ggg gaa ccc ggg 192 Pro Asp Asp Gly Asp Val Pro Leu Ala Leu Leu Arg Gly Glu Pro Gly 50 55 60 ctg cat ttg gcg ccg ggc acc gac gac cac aac cac cac ctc gcg ctg 240 Leu His Leu Ala Pro Gly Thr Asp Asp His Asn His His Leu Ala Leu 65 70 75 80 gac ccc tgc ctc agt gac gag aac tat gac ttt agc tcc gcc gag tcg 288 Asp Pro Cys Leu Ser Asp Glu Asn Tyr Asp Phe Ser Ser Ala Glu Ser 85 90 95 ggc tcc tcg ctg cgc tac tac agc gag ggt gag agc ggc ggc ggc ggc 336 Gly Ser Ser Leu Arg Tyr Tyr Ser Glu Gly Glu Ser Gly Gly Gly Gly 100 105 110 ggc ggc agc tcc ttg tcg ctg cat ccg ccg cag cag cct ccg ctg gtc 384 Gly Gly Ser Ser Leu Ser Leu His Pro Pro Gln Gln Pro Pro Leu Val 115 120 125 ccg acg aac tcg ggg ggc ggc ggc gcg aca gga ggg tcc ccc ggg gaa 432 Pro Thr Asn Ser Gly Gly Gly Gly Ala Thr Gly Gly Ser Pro Gly Glu 130 135 140 agg aaa cgt acc cgg ctt ggc ggc ccg gcg gcc cgg cac cgc tat gag 480 Arg Lys Arg Thr Arg Leu Gly Gly Pro Ala Ala Arg His Arg Tyr Glu 145 150 155 160 gta gtg acg gag ctg ggc ccg gag gag gta cgc tgg ttc tac aag gag 528 Val Val Thr Glu Leu Gly Pro Glu Glu Val Arg Trp Phe Tyr Lys Glu 165 170 175 gac aag aag acc tgg aag ccc ttc atc ggc tac gac tcg ctc cgc atc 576 Asp Lys Lys Thr Trp Lys Pro Phe Ile Gly Tyr Asp Ser Leu Arg Ile 180 185 190 gag ctc gcc ttc cgg acc ctg ctg cag acc acg ggt gcc cgg ccc cag 624 Glu Leu Ala Phe Arg Thr Leu Leu Gln Thr Thr Gly Ala Arg Pro Gln 195 200 205 ggc ggg gac cgg gac ggc gac cat gtg tgc tcc ccc acg agc cca gcc 672 Gly Gly Asp Arg Asp Gly Asp His Val Cys Ser Pro Thr Ser Pro Ala 210 215 220 tcc agt tcc gga gaa gat gac gat gag gac cgc gcc tgc ggc ttc tgc 720 Ser Ser Ser Gly Glu Asp Asp Asp Glu Asp Arg Ala Cys Gly Phe Cys 225 230 235 240 cag agt acg acg ggg cac gag ccg gag atg gtg gag ctt gtg aac atc 768 Gln Ser Thr Thr Gly His Glu Pro Glu Met Val Glu Leu Val Asn Ile 245 250 255 gag cct gtg tgc gtg cgg ggc ggc ctc tac gag gtg gat gtg acc caa 816 Glu Pro Val Cys Val Arg Gly Gly Leu Tyr Glu Val Asp Val Thr Gln 260 265 270 gga gag tgc tac ccg gtg tac tgg aac cag gct gat aaa ata cca gta 864 Gly Glu Cys Tyr Pro Val Tyr Trp Asn Gln Ala Asp Lys Ile Pro Val 275 280 285 atg cgt gga cag tgg ttt att gac ggc act tgg cag cct cta gaa gag 912 Met Arg Gly Gln Trp Phe Ile Asp Gly Thr Trp Gln Pro Leu Glu Glu 290 295 300 gaa gaa agt aat tta att gag caa gaa cat ctc aat tgt ttt agg ggc 960 Glu Glu Ser Asn Leu Ile Glu Gln Glu His Leu Asn Cys Phe Arg Gly 305 310 315 320 cag cag atg cag gaa aat ttc gat att gaa gtg tca aaa tcc ata gat 1008 Gln Gln Met Gln Glu Asn Phe Asp Ile Glu Val Ser Lys Ser Ile Asp 325 330 335 gga aaa gat gct gtt cat agt ttc aag ttg agt cga aac cat gtg gac 1056 Gly Lys Asp Ala Val His Ser Phe Lys Leu Ser Arg Asn His Val Asp 340 345 350 tgg cac agt gtg gat gaa gta tat ctt tat agt gat gca aca aca tct 1104 Trp His Ser Val Asp Glu Val Tyr Leu Tyr Ser Asp Ala Thr Thr Ser 355 360 365 aaa att gca aga aca gtt acc caa aaa ctg gga ttt tct aaa gca tca 1152 Lys Ile Ala Arg Thr Val Thr Gln Lys Leu Gly Phe Ser Lys Ala Ser 370 375 380 agt agt ggt acc aga ctt cat aga ggt tat gta gaa gaa gcc aca tta 1200 Ser Ser Gly Thr Arg Leu His Arg Gly Tyr Val Glu Glu Ala Thr Leu 385 390 395 400 gaa gac aag cca tca cag act acc cat att gta ttt gtt gtg cat ggc 1248 Glu Asp Lys Pro Ser Gln Thr Thr His Ile Val Phe Val Val His Gly 405 410 415 att ggg cag aaa atg gac caa gga aga att atc aaa aat aca gct atg 1296 Ile Gly Gln Lys Met Asp Gln Gly Arg Ile Ile Lys Asn Thr Ala Met 420 425 430 atg aga gaa gct gca aga aaa ata gaa gaa agg cat ttt tcc aac cat 1344 Met Arg Glu Ala Ala Arg Lys Ile Glu Glu Arg His Phe Ser Asn His 435 440 445 gca aca cat gtt gaa ttt ctg cct gtt gag tgg cgg tca aaa ctt act 1392 Ala Thr His Val Glu Phe Leu Pro Val Glu Trp Arg Ser Lys Leu Thr 450 455 460 ctt gat gga gac act gtt gat tcc att act cct gac aaa gta cga ggt 1440 Leu Asp Gly Asp Thr Val Asp Ser Ile Thr Pro Asp Lys Val Arg Gly 465 470 475 480 tta agg gat atg ctg aac agc agt gca atg gac ata atg tat tat act 1488 Leu Arg Asp Met Leu Asn Ser Ser Ala Met Asp Ile Met Tyr Tyr Thr 485 490 495 agt cca ctt tat aga gat gaa cta gtt aaa ggc ctt cag caa gag ctg 1536 Ser Pro Leu Tyr Arg Asp Glu Leu Val Lys Gly Leu Gln Gln Glu Leu 500 505 510 aat cga ttg tat tcc ctt ttc tgt tct cgg aat cca gac ttt gaa gaa 1584 Asn Arg Leu Tyr Ser Leu Phe Cys Ser Arg Asn Pro Asp Phe Glu Glu 515 520 525 aaa ggg ggt aaa gtc tca ata gta tca cat tcc ttg gga tgt gta att 1632 Lys Gly Gly Lys Val Ser Ile Val Ser His Ser Leu Gly Cys Val Ile 530 535 540 act tat gac ata atg act ggc tgg aat cca gtt cgg ctg tat gaa cag 1680 Thr Tyr Asp Ile Met Thr Gly Trp Asn Pro Val Arg Leu Tyr Glu Gln 545 550 555 560 ttg ctg caa aag gaa gaa gag ttg cct gat gaa cga tgg atg agc tat 1728 Leu Leu Gln Lys Glu Glu Glu Leu Pro Asp Glu Arg Trp Met Ser Tyr 565 570 575 gaa gaa cga cat ctt ctt gat gaa ctc tat ata aca aaa cga cgg ctg 1776 Glu Glu Arg His Leu Leu Asp Glu Leu Tyr Ile Thr Lys Arg Arg Leu 580 585 590 aag gaa ata gaa gaa cgg ctt cac gga ttg aaa gca tca tct atg aca 1824 Lys Glu Ile Glu Glu Arg Leu His Gly Leu Lys Ala Ser Ser Met Thr 595 600 605 caa aca cct gcc tta aaa ttt aag gtt gag aat ttc ttc tgt atg gga 1872 Gln Thr Pro Ala Leu Lys Phe Lys Val Glu Asn Phe Phe Cys Met Gly 610 615 620 tcc cca tta gca gtt ttc ttg gcg ttg cgt ggc atc cgc cca gga aat 1920 Ser Pro Leu Ala Val Phe Leu Ala Leu Arg Gly Ile Arg Pro Gly Asn 625 630 635 640 act gga agt caa gac cat att ttg cct aga gag att tgt aac cgg tta 1968 Thr Gly Ser Gln Asp His Ile Leu Pro Arg Glu Ile Cys Asn Arg Leu 645 650 655 cta aat att ttt cat cct aca gat cca gtg gct tat aga tta gaa cca 2016 Leu Asn Ile Phe His Pro Thr Asp Pro Val Ala Tyr Arg Leu Glu Pro 660 665 670 tta ata ctg aaa cac tac agc aac att tca cct gtc cag atc cac tgg 2064 Leu Ile Leu Lys His Tyr Ser Asn Ile Ser Pro Val Gln Ile His Trp 675 680 685 tac aat act tca aat cct tta cct tat gaa cat atg aag cca agc ttt 2112 Tyr Asn Thr Ser Asn Pro Leu Pro Tyr Glu His Met Lys Pro Ser Phe 690 695 700 ctc aac cca gct aaa

gaa cct acc tca gtt tca gag aat gaa ggc att 2160 Leu Asn Pro Ala Lys Glu Pro Thr Ser Val Ser Glu Asn Glu Gly Ile 705 710 715 720 tca acc ata cca agc cct gtg acc tca cca gtt ttg tcc cgc cga cac 2208 Ser Thr Ile Pro Ser Pro Val Thr Ser Pro Val Leu Ser Arg Arg His 725 730 735 tat gga gaa tct ata aca aat ata ggc aaa gca agc ata tta ggg gct 2256 Tyr Gly Glu Ser Ile Thr Asn Ile Gly Lys Ala Ser Ile Leu Gly Ala 740 745 750 gct agc att gga aag gga ctt gga gga atg ttg ttc tca aga ttt gga 2304 Ala Ser Ile Gly Lys Gly Leu Gly Gly Met Leu Phe Ser Arg Phe Gly 755 760 765 cgt tca tct aca aca cag tca tct gaa aca tca aaa gac tca atg gaa 2352 Arg Ser Ser Thr Thr Gln Ser Ser Glu Thr Ser Lys Asp Ser Met Glu 770 775 780 gat gag aag aag cca gtt gcc tca cct tct gct acc acc gta ggg aca 2400 Asp Glu Lys Lys Pro Val Ala Ser Pro Ser Ala Thr Thr Val Gly Thr 785 790 795 800 cag acc ctt cca cat agc agt tct ggc ttc ctc gat tct gca tat ttc 2448 Gln Thr Leu Pro His Ser Ser Ser Gly Phe Leu Asp Ser Ala Tyr Phe 805 810 815 aga ctt caa gaa tcg ttc ttt aat ctc cca caa ctt ctt ttt ccg gaa 2496 Arg Leu Gln Glu Ser Phe Phe Asn Leu Pro Gln Leu Leu Phe Pro Glu 820 825 830 aat gta atg cag aat aaa gat aat gcc ctc gtg gag ttg gat cac agg 2544 Asn Val Met Gln Asn Lys Asp Asn Ala Leu Val Glu Leu Asp His Arg 835 840 845 att gat ttt gaa ctc aga gaa ggc ctt gtg gag agc cgc tat tgg tca 2592 Ile Asp Phe Glu Leu Arg Glu Gly Leu Val Glu Ser Arg Tyr Trp Ser 850 855 860 gct gtc acg tcg cat act gcc tat tgg tca tcc ttg gat gtt gcc ctt 2640 Ala Val Thr Ser His Thr Ala Tyr Trp Ser Ser Leu Asp Val Ala Leu 865 870 875 880 ttt ctt tta acc ttc atg tat aaa cat gag cac gat gat gat gca aaa 2688 Phe Leu Leu Thr Phe Met Tyr Lys His Glu His Asp Asp Asp Ala Lys 885 890 895 ccc aat tta gat cca atc 2706 Pro Asn Leu Asp Pro Ile 900 7 2625 DNA Bos taurus 7 atgaattacc cgggccatgg gtctccgcgg agctccgagc gtaacggcgg ccggggcggc 60 gacggcgccg cctgggagct gggctcggac acggaacccg cgttcggggg cagcgtctgc 120 cgcttcgacc acctgccagt cggggagcct ggcgatgacg aggtgcccct ggccctgctg 180 cgcggggagc ccgggctgca cttggcgccg ggagcggagg accacaacca tcacctggcg 240 ctggacccct gcctcagtga cgataactat gacttcagct cggccgagtc gggctcctcg 300 ctgcgctact acagcgaggg cgagagtgga ggcggcggca gctcctcgtc gctgcacccg 360 cctcagcagc cgctggtccc gtcgaactcg gggggcggcg gggcggctgg aggaggcccc 420 ggtgagagga agcgcacccg gcccggcggc gcggccgccc ggcacagata cgaggtggtg 480 acggagctgg gcccggagga ggtgcgctgg ttctacaagg aggacaagaa gacctggaag 540 cccttcatcg gctacgactc gctccgcatc gagcttgcct tccgaacgct actgcaggcc 600 acgggggccc gagcccgggc ccaagacccg gacggcgacc atgtgtgcgg cccggcctca 660 cccgcgggtc cggcctccag ctccgtggag gacgaagacg aggaccgcgt ctgcggcttc 720 tgcccgcgca ttgcgggcca cgggcgcgag atggaggagc tggtgaacat cgagcgggtg 780 tgtgtgcggg gcggcctcta cgaggtggat gtgacccaag gagaatgcta cccggtgtac 840 tggaaccagt ctgataaaat accagtaatg cgtggacagt ggtttattga tggtacctgg 900 cagccactag aagaagaaga aagtaattta attgagcaag aacatcttag ccgttttaga 960 ggacagcaga tgcaggaaag ttttgatatt gaagtgtcga aacccataga tggaaaagat 1020 gctattcata gtttcaaatt gagtcgaaac cacgtggact ggcacagtgt ggatgaagta 1080 tatctttata gtgatgcaac aacatccaaa attgcaagaa cagttactca aaaactggga 1140 ttttctaaag catcaagtag tgggaccaga cttcatagag gttatgtaga agaagcgaca 1200 ttagaagaca agccatctca gactacccat atcgtatttg ttgtgcatgg cattggacag 1260 aaaatggacc aaggaagaat tatcaaaaat actgccatga tgagagaggc tgcaagaaaa 1320 atagaagaaa ggcatttttc caaccatgca acacatgttg aatttctgcc tgttgagtgg 1380 cggtcaaaac ttactcttga tggagacact gttgattcca ttactccaga caaagtgcga 1440 ggtttaaggg atatgttaaa cagcagtgca atggacataa tgtattatac tagcccactg 1500 tatagagatg aactagttaa aggccttcag caagagctca atcgattata ttcccttttc 1560 tgttcccgga atccaaactt tgaggaaaaa gggggtaaag tctcaatagt gtcacattcc 1620 ttgggatgtg tgatcactta tgacataatg actggctgga atccagttcg actctatgaa 1680 cagttgctgc agaaggaaga agagttgcct gatgaacgat ggatgagcta cgaagaacgt 1740 catcttcttg atgaactcta tataacaaaa cgacggctac gagaaattga agaacggcta 1800 catggattga aagcatcatc tatgacacaa acacctgcct taaaatttaa ggttgaaaat 1860 ttcttctgta tgggatcccc actagcagtt tttttggcac tgcgtggcat ccgcccagga 1920 aacactggaa gtcaagacca tattttgccc agagagattt gtaaccgatt actaaacatt 1980 ttccatccaa cagatccagt ggcttataga ttagaaccat taatactgaa acactacagc 2040 aacatttcac ctgtgcagat ccactggtat aatacatcca atcctctacc ttatgagtat 2100 atgaagccaa gctttcttca cccagcgaaa gatcctacct caatttcaga gaatgaaggc 2160 atctcaacaa taccaagccc tgtgacttcg ccagtcttgt ctcgccgaca ctatggggaa 2220 tctataacaa atataggcaa agcaagcata ttaggggctg caagcattgg aaagggactt 2280 ggaggaatgt tgttctcaag atttggacgt tcatctgcat cacagccatc tgagacatca 2340 agggactcca tagaagacga gaagaagcca gttgcctccc cgcccatgac caccgtggca 2400 acgcagaccc ttccacacag cagttctggc tttcttgact ctgcattgga actggatcac 2460 agaattgact ttgaactcag agaaggcctt gtggagagcc gctattggtc agctgtcacg 2520 tcgcatactg cctattggtc atccttggat gttgccctct tcctgttaac cttcatgtac 2580 aaacacgagc acgataataa tgtgaaaccc agtttagatc cagtc 2625 8 875 PRT Bos taurus 8 Met Asn Tyr Pro Gly His Gly Ser Pro Arg Ser Ser Glu Arg Asn Gly 1 5 10 15 Gly Arg Gly Gly Asp Gly Ala Ala Trp Glu Leu Gly Ser Asp Thr Glu 20 25 30 Pro Ala Phe Gly Gly Ser Val Cys Arg Phe Asp His Leu Pro Val Gly 35 40 45 Glu Pro Gly Asp Asp Glu Val Pro Leu Ala Leu Leu Arg Gly Glu Pro 50 55 60 Gly Leu His Leu Ala Pro Gly Ala Glu Asp His Asn His His Leu Ala 65 70 75 80 Leu Asp Pro Cys Leu Ser Asp Asp Asn Tyr Asp Phe Ser Ser Ala Glu 85 90 95 Ser Gly Ser Ser Leu Arg Tyr Tyr Ser Glu Gly Glu Ser Gly Gly Gly 100 105 110 Gly Ser Ser Ser Ser Leu His Pro Pro Gln Gln Pro Leu Val Pro Ser 115 120 125 Asn Ser Gly Gly Gly Gly Ala Ala Gly Gly Gly Pro Gly Glu Arg Lys 130 135 140 Arg Thr Arg Pro Gly Gly Ala Ala Ala Arg His Arg Tyr Glu Val Val 145 150 155 160 Thr Glu Leu Gly Pro Glu Glu Val Arg Trp Phe Tyr Lys Glu Asp Lys 165 170 175 Lys Thr Trp Lys Pro Phe Ile Gly Tyr Asp Ser Leu Arg Ile Glu Leu 180 185 190 Ala Phe Arg Thr Leu Leu Gln Ala Thr Gly Ala Arg Ala Arg Ala Gln 195 200 205 Asp Pro Asp Gly Asp His Val Cys Gly Pro Ala Ser Pro Ala Gly Pro 210 215 220 Ala Ser Ser Ser Val Glu Asp Glu Asp Glu Asp Arg Val Cys Gly Phe 225 230 235 240 Cys Pro Arg Ile Ala Gly His Gly Arg Glu Met Glu Glu Leu Val Asn 245 250 255 Ile Glu Arg Val Cys Val Arg Gly Gly Leu Tyr Glu Val Asp Val Thr 260 265 270 Gln Gly Glu Cys Tyr Pro Val Tyr Trp Asn Gln Ser Asp Lys Ile Pro 275 280 285 Val Met Arg Gly Gln Trp Phe Ile Asp Gly Thr Trp Gln Pro Leu Glu 290 295 300 Glu Glu Glu Ser Asn Leu Ile Glu Gln Glu His Leu Ser Arg Phe Arg 305 310 315 320 Gly Gln Gln Met Gln Glu Ser Phe Asp Ile Glu Val Ser Lys Pro Ile 325 330 335 Asp Gly Lys Asp Ala Ile His Ser Phe Lys Leu Ser Arg Asn His Val 340 345 350 Asp Trp His Ser Val Asp Glu Val Tyr Leu Tyr Ser Asp Ala Thr Thr 355 360 365 Ser Lys Ile Ala Arg Thr Val Thr Gln Lys Leu Gly Phe Ser Lys Ala 370 375 380 Ser Ser Ser Gly Thr Arg Leu His Arg Gly Tyr Val Glu Glu Ala Thr 385 390 395 400 Leu Glu Asp Lys Pro Ser Gln Thr Thr His Ile Val Phe Val Val His 405 410 415 Gly Ile Gly Gln Lys Met Asp Gln Gly Arg Ile Ile Lys Asn Thr Ala 420 425 430 Met Met Arg Glu Ala Ala Arg Lys Ile Glu Glu Arg His Phe Ser Asn 435 440 445 His Ala Thr His Val Glu Phe Leu Pro Val Glu Trp Arg Ser Lys Leu 450 455 460 Thr Leu Asp Gly Asp Thr Val Asp Ser Ile Thr Pro Asp Lys Val Arg 465 470 475 480 Gly Leu Arg Asp Met Leu Asn Ser Ser Ala Met Asp Ile Met Tyr Tyr 485 490 495 Thr Ser Pro Leu Tyr Arg Asp Glu Leu Val Lys Gly Leu Gln Gln Glu 500 505 510 Leu Asn Arg Leu Tyr Ser Leu Phe Cys Ser Arg Asn Pro Asn Phe Glu 515 520 525 Glu Lys Gly Gly Lys Val Ser Ile Val Ser His Ser Leu Gly Cys Val 530 535 540 Ile Thr Tyr Asp Ile Met Thr Gly Trp Asn Pro Val Arg Leu Tyr Glu 545 550 555 560 Gln Leu Leu Gln Lys Glu Glu Glu Leu Pro Asp Glu Arg Trp Met Ser 565 570 575 Tyr Glu Glu Arg His Leu Leu Asp Glu Leu Tyr Ile Thr Lys Arg Arg 580 585 590 Leu Arg Glu Ile Glu Glu Arg Leu His Gly Leu Lys Ala Ser Ser Met 595 600 605 Thr Gln Thr Pro Ala Leu Lys Phe Lys Val Glu Asn Phe Phe Cys Met 610 615 620 Gly Ser Pro Leu Ala Val Phe Leu Ala Leu Arg Gly Ile Arg Pro Gly 625 630 635 640 Asn Thr Gly Ser Gln Asp His Ile Leu Pro Arg Glu Ile Cys Asn Arg 645 650 655 Leu Leu Asn Ile Phe His Pro Thr Asp Pro Val Ala Tyr Arg Leu Glu 660 665 670 Pro Leu Ile Leu Lys His Tyr Ser Asn Ile Ser Pro Val Gln Ile His 675 680 685 Trp Tyr Asn Thr Ser Asn Pro Leu Pro Tyr Glu Tyr Met Lys Pro Ser 690 695 700 Phe Leu His Pro Ala Lys Asp Pro Thr Ser Ile Ser Glu Asn Glu Gly 705 710 715 720 Ile Ser Thr Ile Pro Ser Pro Val Thr Ser Pro Val Leu Ser Arg Arg 725 730 735 His Tyr Gly Glu Ser Ile Thr Asn Ile Gly Lys Ala Ser Ile Leu Gly 740 745 750 Ala Ala Ser Ile Gly Lys Gly Leu Gly Gly Met Leu Phe Ser Arg Phe 755 760 765 Gly Arg Ser Ser Ala Ser Gln Pro Ser Glu Thr Ser Arg Asp Ser Ile 770 775 780 Glu Asp Glu Lys Lys Pro Val Ala Ser Pro Pro Met Thr Thr Val Ala 785 790 795 800 Thr Gln Thr Leu Pro His Ser Ser Ser Gly Phe Leu Asp Ser Ala Leu 805 810 815 Glu Leu Asp His Arg Ile Asp Phe Glu Leu Arg Glu Gly Leu Val Glu 820 825 830 Ser Arg Tyr Trp Ser Ala Val Thr Ser His Thr Ala Tyr Trp Ser Ser 835 840 845 Leu Asp Val Ala Leu Phe Leu Leu Thr Phe Met Tyr Lys His Glu His 850 855 860 Asp Asn Asn Val Lys Pro Ser Leu Asp Pro Val 865 870 875 9 5 PRT Artificial Sequence Consensus amino acid sequence 9 Ser His Ser Leu Gly 1 5 10 5 PRT Artificial Sequence Consensus amino acid sequence VARIANT (1)...(2) Xaa = Any Amino Acid VARIANT (4)...(4) Xaa = Any Amino Acid 10 Xaa Xaa Ser Xaa Gly 1 5 11 1921 DNA Homo sapiens CDS (33)...(1391) 11 cctgttgctg atgctgccgt gcggtacttg tc atg gag ctg gca ctg cgg cgc 53 Met Glu Leu Ala Leu Arg Arg 1 5 tct ccc gtc ccg cgg tgg ttg ctg ctg ctg ccg ctg ctg ctg ggc ctg 101 Ser Pro Val Pro Arg Trp Leu Leu Leu Leu Pro Leu Leu Leu Gly Leu 10 15 20 aac gca gga gct gtc att gac tgg ccc aca gag gag ggc aag gaa gta 149 Asn Ala Gly Ala Val Ile Asp Trp Pro Thr Glu Glu Gly Lys Glu Val 25 30 35 tgg gat tat gtg acg gtc cgc aag gat gcc tac atg ttc tgg tgg ctc 197 Trp Asp Tyr Val Thr Val Arg Lys Asp Ala Tyr Met Phe Trp Trp Leu 40 45 50 55 tat tat gcc acc aac tcc tgc aag aac ttc tca gaa ctg ccc ctg gtc 245 Tyr Tyr Ala Thr Asn Ser Cys Lys Asn Phe Ser Glu Leu Pro Leu Val 60 65 70 atg tgg ctt cag ggc ggt cca ggc ggt tct agc act gga ttt gga aac 293 Met Trp Leu Gln Gly Gly Pro Gly Gly Ser Ser Thr Gly Phe Gly Asn 75 80 85 ttt gag gaa att ggg ccc ctt gac agt gat ctc aaa cca cgg aaa acc 341 Phe Glu Glu Ile Gly Pro Leu Asp Ser Asp Leu Lys Pro Arg Lys Thr 90 95 100 acc tgg ctc cag gct gcc agt ctc cta ttt gtg gat aat ccc gtg ggc 389 Thr Trp Leu Gln Ala Ala Ser Leu Leu Phe Val Asp Asn Pro Val Gly 105 110 115 act ggg ttc agt tat gtg aat ggt agt ggt gcc tat gcc aag gac ctg 437 Thr Gly Phe Ser Tyr Val Asn Gly Ser Gly Ala Tyr Ala Lys Asp Leu 120 125 130 135 gct atg gtg gct tca gac atg atg gtt ctc ctg aag acc ttc ttc agt 485 Ala Met Val Ala Ser Asp Met Met Val Leu Leu Lys Thr Phe Phe Ser 140 145 150 tgc cac aaa gaa ttc cag aca gtt cca ttc tac att ttc tca gag tcc 533 Cys His Lys Glu Phe Gln Thr Val Pro Phe Tyr Ile Phe Ser Glu Ser 155 160 165 tat gga gga aaa atg gca gct ggc att ggt cta gag ctt tat aag gcc 581 Tyr Gly Gly Lys Met Ala Ala Gly Ile Gly Leu Glu Leu Tyr Lys Ala 170 175 180 att cag cga ggg acc atc aag tgc aac ttt gcg ggg gtt gcc ttg ggt 629 Ile Gln Arg Gly Thr Ile Lys Cys Asn Phe Ala Gly Val Ala Leu Gly 185 190 195 gat tcc tgg atc tcc ccc gtg gat tcg gtg ctc tcc tgg gga cct tac 677 Asp Ser Trp Ile Ser Pro Val Asp Ser Val Leu Ser Trp Gly Pro Tyr 200 205 210 215 ctg tac agc atg tct ctt ctc gaa gac aaa ggt ctg gca gag gtg tct 725 Leu Tyr Ser Met Ser Leu Leu Glu Asp Lys Gly Leu Ala Glu Val Ser 220 225 230 aag gtt gca gag caa gta ctg aat gcc gta aat aag ggg ctc tac aga 773 Lys Val Ala Glu Gln Val Leu Asn Ala Val Asn Lys Gly Leu Tyr Arg 235 240 245 gag gcc aca gag ctg tgg ggg aaa gca gaa atg atc att gaa cag aac 821 Glu Ala Thr Glu Leu Trp Gly Lys Ala Glu Met Ile Ile Glu Gln Asn 250 255 260 aca gat ggg gtg aac ttc tat aac atc tta act aaa agc act ccc acg 869 Thr Asp Gly Val Asn Phe Tyr Asn Ile Leu Thr Lys Ser Thr Pro Thr 265 270 275 tct aca atg gag tcg agt cta gaa ttc aca cag agc cac cta gtt tgt 917 Ser Thr Met Glu Ser Ser Leu Glu Phe Thr Gln Ser His Leu Val Cys 280 285 290 295 ctt tgt cag cgc cac gtg aga cac cta caa cga gat gcc tta agc cag 965 Leu Cys Gln Arg His Val Arg His Leu Gln Arg Asp Ala Leu Ser Gln 300 305 310 ctc atg aat ggc ccc atc aga aag aag ctc aaa att att cct gag gat 1013 Leu Met Asn Gly Pro Ile Arg Lys Lys Leu Lys Ile Ile Pro Glu Asp 315 320 325 caa tcc tgg gga ggc cag gct acc aac gtc ttt gtg aac atg gag gag 1061 Gln Ser Trp Gly Gly Gln Ala Thr Asn Val Phe Val Asn Met Glu Glu 330 335 340 gac ttc atg aag cca gtc att agc att gtg gac gag ttg ctg gag gca 1109 Asp Phe Met Lys Pro Val Ile Ser Ile Val Asp Glu Leu Leu Glu Ala 345 350 355 ggg atc aac gtg acg gtg tat aat gga cag ctg gat ctc atc gta gat 1157 Gly Ile Asn Val Thr Val Tyr Asn Gly Gln Leu Asp Leu Ile Val Asp 360 365 370 375 acc atg ggt cag gag gcc tgg gtg cgg aaa ctg aag tgg cca gaa ctg 1205 Thr Met Gly Gln Glu Ala Trp Val Arg Lys Leu Lys Trp Pro Glu Leu 380 385 390 cct aaa ttc agt cag ctg aag tgg aag gcc ctg tac agt gac cct aaa 1253 Pro Lys Phe Ser Gln Leu Lys Trp Lys Ala Leu Tyr Ser Asp Pro Lys 395 400 405 tct ttg gaa aca tct gct ttt gtc aag tcc tac aag aac ctt gct ttc 1301 Ser Leu Glu Thr Ser Ala Phe Val Lys Ser Tyr Lys Asn Leu Ala Phe 410 415 420 tac tgg att ctg aaa gct ggt cat atg gtt cct tct gac caa ggg gac 1349 Tyr Trp Ile Leu Lys Ala Gly His Met Val Pro Ser Asp Gln Gly Asp 425 430 435 atg gct ctg aag atg atg aga ctg gtg act cag caa gaa tag 1391 Met Ala Leu Lys Met Met Arg Leu Val Thr Gln Gln Glu * 440 445 450 gatggatggg gctggagatg agctggtttg gccttggggc acagagctga gctgaggccg 1451 ctgaagctgt aggaagcgcc attcttccct gtatctaact ggggctgtga tcaagaaggt 1511 tctgaccagc ttctgcagag gataaaatca ttgtctctgg aggcaatttg gaaattattt 1571 ctgcttctta

aaaaaaccta agatttttta aaaaattgat ttgttttgat caaaataaag 1631 gatgataata gatattattt tttcttatga cagaagcaaa tgatgtgatt tatagaaaaa 1691 ctgggaaata caggtaccca aagagtaaat caacatctgt ataccccctt cccaggggta 1751 agcactgtta ccaatttagc atatgtcctt gcagaatttt tttttctata tatacatata 1811 tattttttac caaaatgaat cattactcta tgttgtttta ctatttgttt gacatatcag 1871 tatatctgaa acaccttttc atgtcaataa atgttcttct ctaacattaa 1921 12 452 PRT Homo sapiens 12 Met Glu Leu Ala Leu Arg Arg Ser Pro Val Pro Arg Trp Leu Leu Leu 1 5 10 15 Leu Pro Leu Leu Leu Gly Leu Asn Ala Gly Ala Val Ile Asp Trp Pro 20 25 30 Thr Glu Glu Gly Lys Glu Val Trp Asp Tyr Val Thr Val Arg Lys Asp 35 40 45 Ala Tyr Met Phe Trp Trp Leu Tyr Tyr Ala Thr Asn Ser Cys Lys Asn 50 55 60 Phe Ser Glu Leu Pro Leu Val Met Trp Leu Gln Gly Gly Pro Gly Gly 65 70 75 80 Ser Ser Thr Gly Phe Gly Asn Phe Glu Glu Ile Gly Pro Leu Asp Ser 85 90 95 Asp Leu Lys Pro Arg Lys Thr Thr Trp Leu Gln Ala Ala Ser Leu Leu 100 105 110 Phe Val Asp Asn Pro Val Gly Thr Gly Phe Ser Tyr Val Asn Gly Ser 115 120 125 Gly Ala Tyr Ala Lys Asp Leu Ala Met Val Ala Ser Asp Met Met Val 130 135 140 Leu Leu Lys Thr Phe Phe Ser Cys His Lys Glu Phe Gln Thr Val Pro 145 150 155 160 Phe Tyr Ile Phe Ser Glu Ser Tyr Gly Gly Lys Met Ala Ala Gly Ile 165 170 175 Gly Leu Glu Leu Tyr Lys Ala Ile Gln Arg Gly Thr Ile Lys Cys Asn 180 185 190 Phe Ala Gly Val Ala Leu Gly Asp Ser Trp Ile Ser Pro Val Asp Ser 195 200 205 Val Leu Ser Trp Gly Pro Tyr Leu Tyr Ser Met Ser Leu Leu Glu Asp 210 215 220 Lys Gly Leu Ala Glu Val Ser Lys Val Ala Glu Gln Val Leu Asn Ala 225 230 235 240 Val Asn Lys Gly Leu Tyr Arg Glu Ala Thr Glu Leu Trp Gly Lys Ala 245 250 255 Glu Met Ile Ile Glu Gln Asn Thr Asp Gly Val Asn Phe Tyr Asn Ile 260 265 270 Leu Thr Lys Ser Thr Pro Thr Ser Thr Met Glu Ser Ser Leu Glu Phe 275 280 285 Thr Gln Ser His Leu Val Cys Leu Cys Gln Arg His Val Arg His Leu 290 295 300 Gln Arg Asp Ala Leu Ser Gln Leu Met Asn Gly Pro Ile Arg Lys Lys 305 310 315 320 Leu Lys Ile Ile Pro Glu Asp Gln Ser Trp Gly Gly Gln Ala Thr Asn 325 330 335 Val Phe Val Asn Met Glu Glu Asp Phe Met Lys Pro Val Ile Ser Ile 340 345 350 Val Asp Glu Leu Leu Glu Ala Gly Ile Asn Val Thr Val Tyr Asn Gly 355 360 365 Gln Leu Asp Leu Ile Val Asp Thr Met Gly Gln Glu Ala Trp Val Arg 370 375 380 Lys Leu Lys Trp Pro Glu Leu Pro Lys Phe Ser Gln Leu Lys Trp Lys 385 390 395 400 Ala Leu Tyr Ser Asp Pro Lys Ser Leu Glu Thr Ser Ala Phe Val Lys 405 410 415 Ser Tyr Lys Asn Leu Ala Phe Tyr Trp Ile Leu Lys Ala Gly His Met 420 425 430 Val Pro Ser Asp Gln Gly Asp Met Ala Leu Lys Met Met Arg Leu Val 435 440 445 Thr Gln Gln Glu 450 13 1359 DNA Homo sapiens CDS (1)...(1359) 13 atg gag ctg gca ctg cgg cgc tct ccc gtc ccg cgg tgg ttg ctg ctg 48 Met Glu Leu Ala Leu Arg Arg Ser Pro Val Pro Arg Trp Leu Leu Leu 1 5 10 15 ctg ccg ctg ctg ctg ggc ctg aac gca gga gct gtc att gac tgg ccc 96 Leu Pro Leu Leu Leu Gly Leu Asn Ala Gly Ala Val Ile Asp Trp Pro 20 25 30 aca gag gag ggc aag gaa gta tgg gat tat gtg acg gtc cgc aag gat 144 Thr Glu Glu Gly Lys Glu Val Trp Asp Tyr Val Thr Val Arg Lys Asp 35 40 45 gcc tac atg ttc tgg tgg ctc tat tat gcc acc aac tcc tgc aag aac 192 Ala Tyr Met Phe Trp Trp Leu Tyr Tyr Ala Thr Asn Ser Cys Lys Asn 50 55 60 ttc tca gaa ctg ccc ctg gtc atg tgg ctt cag ggc ggt cca ggc ggt 240 Phe Ser Glu Leu Pro Leu Val Met Trp Leu Gln Gly Gly Pro Gly Gly 65 70 75 80 tct agc act gga ttt gga aac ttt gag gaa att ggg ccc ctt gac agt 288 Ser Ser Thr Gly Phe Gly Asn Phe Glu Glu Ile Gly Pro Leu Asp Ser 85 90 95 gat ctc aaa cca cgg aaa acc acc tgg ctc cag gct gcc agt ctc cta 336 Asp Leu Lys Pro Arg Lys Thr Thr Trp Leu Gln Ala Ala Ser Leu Leu 100 105 110 ttt gtg gat aat ccc gtg ggc act ggg ttc agt tat gtg aat ggt agt 384 Phe Val Asp Asn Pro Val Gly Thr Gly Phe Ser Tyr Val Asn Gly Ser 115 120 125 ggt gcc tat gcc aag gac ctg gct atg gtg gct tca gac atg atg gtt 432 Gly Ala Tyr Ala Lys Asp Leu Ala Met Val Ala Ser Asp Met Met Val 130 135 140 ctc ctg aag acc ttc ttc agt tgc cac aaa gaa ttc cag aca gtt cca 480 Leu Leu Lys Thr Phe Phe Ser Cys His Lys Glu Phe Gln Thr Val Pro 145 150 155 160 ttc tac att ttc tca gag tcc tat gga gga aaa atg gca gct ggc att 528 Phe Tyr Ile Phe Ser Glu Ser Tyr Gly Gly Lys Met Ala Ala Gly Ile 165 170 175 ggt cta gag ctt tat aag gcc att cag cga ggg acc atc aag tgc aac 576 Gly Leu Glu Leu Tyr Lys Ala Ile Gln Arg Gly Thr Ile Lys Cys Asn 180 185 190 ttt gcg ggg gtt gcc ttg ggt gat tcc tgg atc tcc ccc gtg gat tcg 624 Phe Ala Gly Val Ala Leu Gly Asp Ser Trp Ile Ser Pro Val Asp Ser 195 200 205 gtg ctc tcc tgg gga cct tac ctg tac agc atg tct ctt ctc gaa gac 672 Val Leu Ser Trp Gly Pro Tyr Leu Tyr Ser Met Ser Leu Leu Glu Asp 210 215 220 aaa ggt ctg gca gag gtg tct aag gtt gca gag caa gta ctg aat gcc 720 Lys Gly Leu Ala Glu Val Ser Lys Val Ala Glu Gln Val Leu Asn Ala 225 230 235 240 gta aat aag ggg ctc tac aga gag gcc aca gag ctg tgg ggg aaa gca 768 Val Asn Lys Gly Leu Tyr Arg Glu Ala Thr Glu Leu Trp Gly Lys Ala 245 250 255 gaa atg atc att gaa cag aac aca gat ggg gtg aac ttc tat aac atc 816 Glu Met Ile Ile Glu Gln Asn Thr Asp Gly Val Asn Phe Tyr Asn Ile 260 265 270 tta act aaa agc act ccc acg tct aca atg gag tcg agt cta gaa ttc 864 Leu Thr Lys Ser Thr Pro Thr Ser Thr Met Glu Ser Ser Leu Glu Phe 275 280 285 aca cag agc cac cta gtt tgt ctt tgt cag cgc cac gtg aga cac cta 912 Thr Gln Ser His Leu Val Cys Leu Cys Gln Arg His Val Arg His Leu 290 295 300 caa cga gat gcc tta agc cag ctc atg aat ggc ccc atc aga aag aag 960 Gln Arg Asp Ala Leu Ser Gln Leu Met Asn Gly Pro Ile Arg Lys Lys 305 310 315 320 ctc aaa att att cct gag gat caa tcc tgg gga ggc cag gct acc aac 1008 Leu Lys Ile Ile Pro Glu Asp Gln Ser Trp Gly Gly Gln Ala Thr Asn 325 330 335 gtc ttt gtg aac atg gag gag gac ttc atg aag cca gtc att agc att 1056 Val Phe Val Asn Met Glu Glu Asp Phe Met Lys Pro Val Ile Ser Ile 340 345 350 gtg gac gag ttg ctg gag gca ggg atc aac gtg acg gtg tat aat gga 1104 Val Asp Glu Leu Leu Glu Ala Gly Ile Asn Val Thr Val Tyr Asn Gly 355 360 365 cag ctg gat ctc atc gta gat acc atg ggt cag gag gcc tgg gtg cgg 1152 Gln Leu Asp Leu Ile Val Asp Thr Met Gly Gln Glu Ala Trp Val Arg 370 375 380 aaa ctg aag tgg cca gaa ctg cct aaa ttc agt cag ctg aag tgg aag 1200 Lys Leu Lys Trp Pro Glu Leu Pro Lys Phe Ser Gln Leu Lys Trp Lys 385 390 395 400 gcc ctg tac agt gac cct aaa tct ttg gaa aca tct gct ttt gtc aag 1248 Ala Leu Tyr Ser Asp Pro Lys Ser Leu Glu Thr Ser Ala Phe Val Lys 405 410 415 tcc tac aag aac ctt gct ttc tac tgg att ctg aaa gct ggt cat atg 1296 Ser Tyr Lys Asn Leu Ala Phe Tyr Trp Ile Leu Lys Ala Gly His Met 420 425 430 gtt cct tct gac caa ggg gac atg gct ctg aag atg atg aga ctg gtg 1344 Val Pro Ser Asp Gln Gly Asp Met Ala Leu Lys Met Met Arg Leu Val 435 440 445 act cag caa gaa tag 1359 Thr Gln Gln Glu * 450 14 209 PRT Homo sapiens VARIANT (22)...(24) Xaa = Any Amino Acid 14 Tyr Leu Thr Val Asn Asp Thr His Gly Lys Asn Leu Phe Tyr Trp Phe 1 5 10 15 Phe Glu Ser Arg Asn Xaa Xaa Xaa Asp Pro Lys Gln Asp Pro Val Val 20 25 30 Leu Trp Leu Asn Gly Gly Pro Gly Cys Ser Ser Leu Leu Phe Tyr Glu 35 40 45 Asn Gly Pro Phe Ser Ile Ser Ser Asp Gly Ser Lys Ser Leu Pro Ser 50 55 60 Leu Ser Leu Asn Pro Tyr Ser Trp Asn Asn Val Ala Asn Met Ile Tyr 65 70 75 80 Leu Asp Gln Pro Val Gly Val Gly Phe Ser Tyr Ser Asp Ser Asp Asp 85 90 95 Asp Tyr Thr Thr Thr Asn Asp Val Glu Ala Ala Lys Asp Leu Tyr Asn 100 105 110 Phe Leu Gln Asp Phe Phe Gln Leu Phe Pro Glu Leu Leu Lys Asn Asp 115 120 125 Phe Tyr Ile Ala Gly Glu Ser Tyr Ala Gly His Tyr Ile Pro Thr Phe 130 135 140 Ala Ser Glu Ile Val Gln Gly Asn Lys Lys Asn Pro Gly Pro Asn Ile 145 150 155 160 Asn Leu Lys Gly Leu Ala Ile Gly Asn Gly Leu Thr Asp Pro Leu Ile 165 170 175 Gln Tyr Asn Ala Tyr Val Pro Phe Ala Tyr Glu His Gly Gly Glu Leu 180 185 190 Ser Val Leu Ile Ser Glu Glu Tyr Ser Lys Ile Ser Lys Ser Phe Pro 195 200 205 Arg 15 119 PRT Homo sapiens 15 Val Tyr Gln Lys Phe Leu Asp Thr Gly Asp Trp Met Arg Ser Phe Leu 1 5 10 15 Val Lys Leu Leu Ser Leu Leu Glu Gln Gly Tyr Arg Val Leu Ile Tyr 20 25 30 Ala Gly Asp Leu Asp Met Ile Cys Asn Trp Leu Gly Asn Glu Ala Trp 35 40 45 Val Asn Ser Leu Glu Trp Ser Gly Lys Lys Gln Phe Gln Ala Ser Ser 50 55 60 Trp Arg Pro Trp Leu Val Asp Gly Ala Asp Ser Glu Gln Val Ala Gly 65 70 75 80 Phe Val Lys Thr Tyr Glu Lys His Leu Thr Phe Leu Thr Val Arg Gly 85 90 95 Ala Gly His Met Val Pro Tyr Asp Lys Pro Gln Ala Ala Leu Gln Met 100 105 110 Val Lys Arg Trp Ile Ala Gly 115 16 8 PRT Artificial Sequence Consensus amino acid sequence VARIANT (1)...(1) Xaa at postion 1 can be L, I, V or M VARIANT (2)...(2) Xaa = Any Amino Acid VARIANT (3)...(3) Xaa at postion 3 can be G, T or A VARIANT (7)...(7) Xaa at position 7 can be A or G VARIANT (8)...(8) Xaa at position 8 can be G or S 16 Xaa Xaa Xaa Glu Ser Tyr Xaa Xaa 1 5 17 18 PRT Artificial Sequence Consensus amino acid sequence VARIANT (1)...(1) Xaa at position 1 can be L, I, V or F VARIANT (2)...(3) Xaa = Any Amino Acid VARIANT (4)...(4) Xaa at position 4 can be L, I, V, S, T or A VARIANT (5)...(5) Xaa = Any Amino Acid VARIANT (6)...(6) Xaa at position 6 can be I, V, P, S or T VARIANT (7)...(7) Xaa = Any Amino Acid VARIANT (8)...(8) Xaa at position 8 can be G, S, D, N, Q or L VARIANT (9)...(9) Xaa at position 9 can be S, A, G or V VARIANT (10)...(10) Xaa at position 9 can be S or G VARIANT (12)...(12) Xaa = Any Amino Acid VARIANT (13)...(13) Xaa at position 9 can be I, V, A or Q VARIANT (15)...(17) Xaa = Any Amino Acid VARIANT (18)...(18) Xaa at position 18 can be P, S or A 17 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa His Xaa Xaa Pro Xaa Xaa 1 5 10 15 Xaa Xaa 18 8 PRT Artificial Sequence Consensus amino acid sequence 18 Ile Phe Ser Glu Ser Tyr Gly Gly 1 5 19 14 PRT Artificial Sequence Consensus amino acid sequence 19 Leu Ala Phe Tyr Trp Ile Leu Lys Ala Gly His Met Val Pro 1 5 10 20 980 DNA Homo sapiens CDS (18)...(800) 20 cctgtggtcg ccccagg atg ctg aac cga atg gtg ggc ggg cag gac acg 50 Met Leu Asn Arg Met Val Gly Gly Gln Asp Thr 1 5 10 cag gag ggc gag tgg ccc tgg caa gtc agc atc cag cgc aac gga agc 98 Gln Glu Gly Glu Trp Pro Trp Gln Val Ser Ile Gln Arg Asn Gly Ser 15 20 25 cac ttc tgc ggg ggc agc ctc atc gcg gag cag tgg gtc ctg acg gct 146 His Phe Cys Gly Gly Ser Leu Ile Ala Glu Gln Trp Val Leu Thr Ala 30 35 40 gcg cac tgc ttc cgc aac acc tct gag acg tcc ctg tac cag gtc ctg 194 Ala His Cys Phe Arg Asn Thr Ser Glu Thr Ser Leu Tyr Gln Val Leu 45 50 55 ctg ggg gca agg cag cta gtg cag ccg gga cca cac gct atg tat gcc 242 Leu Gly Ala Arg Gln Leu Val Gln Pro Gly Pro His Ala Met Tyr Ala 60 65 70 75 cgg gtg agg cag gtg gag agc aac ccc ctg tac cag ggc acg gcc tcc 290 Arg Val Arg Gln Val Glu Ser Asn Pro Leu Tyr Gln Gly Thr Ala Ser 80 85 90 agc gct gac gtg gcc ctg gtg gag ctg gag gca cca gtg ccc ttc acc 338 Ser Ala Asp Val Ala Leu Val Glu Leu Glu Ala Pro Val Pro Phe Thr 95 100 105 aat tac atc ctc ccc gtg tgc ctg cct gac ccc tcg gtg atc ttt gag 386 Asn Tyr Ile Leu Pro Val Cys Leu Pro Asp Pro Ser Val Ile Phe Glu 110 115 120 acg ggc atg aac tgc tgg gtc act ggc tgg ggc agc ccc agt gag gaa 434 Thr Gly Met Asn Cys Trp Val Thr Gly Trp Gly Ser Pro Ser Glu Glu 125 130 135 gac ctc ctg ccc gaa ccg cgg atc ctg cag aaa ctc gct gtg ccc atc 482 Asp Leu Leu Pro Glu Pro Arg Ile Leu Gln Lys Leu Ala Val Pro Ile 140 145 150 155 atc gac aca ccc aag tgc aac ctg ctc tac agc aaa gac acc gag ttt 530 Ile Asp Thr Pro Lys Cys Asn Leu Leu Tyr Ser Lys Asp Thr Glu Phe 160 165 170 ggc tac caa ccc aaa acc atc aag aat gac atg ctg tgc gcc ggc ttc 578 Gly Tyr Gln Pro Lys Thr Ile Lys Asn Asp Met Leu Cys Ala Gly Phe 175 180 185 gag gag ggc aag aag gat gcc tgc aag ggc gac tcg ggc ggc ccc ctg 626 Glu Glu Gly Lys Lys Asp Ala Cys Lys Gly Asp Ser Gly Gly Pro Leu 190 195 200 gtg tgc ctc gtg ggt cag tcg tgg ctg cag gcg ggg gtg atc agc tgg 674 Val Cys Leu Val Gly Gln Ser Trp Leu Gln Ala Gly Val Ile Ser Trp 205 210 215 ggt gag ggc tgt gcc cgc cag aac cgc cca ggt gtc tac atc cgt gtc 722 Gly Glu Gly Cys Ala Arg Gln Asn Arg Pro Gly Val Tyr Ile Arg Val 220 225 230 235 acc gcc cac cac aac tgg atc cat cgg atc atc ccc aaa ctg cag ttc 770 Thr Ala His His Asn Trp Ile His Arg Ile Ile Pro Lys Leu Gln Phe 240 245 250 cag cca gcg agg ttg ggc ggc cag aag tga gacccccggg gccaggagcc 820 Gln Pro Ala Arg Leu Gly Gly Gln Lys * 255 260 ccttgagcag agctctgcac ccagcctgcc cgcccacacc atcctgctgg tcctcccagc 880 gctgctgttg cacctgtgag ccccaccaga ctcatttgta aatagcgctc cttcctcccc 940 tctcaaatac ccttatttta tttatgtttc tcccaataaa 980 21 260 PRT Homo sapiens 21 Met Leu Asn Arg Met Val Gly Gly Gln Asp Thr Gln Glu Gly Glu Trp 1 5 10 15 Pro Trp Gln Val Ser Ile Gln Arg Asn Gly Ser His Phe Cys Gly Gly 20 25 30 Ser Leu Ile Ala Glu Gln Trp Val Leu Thr Ala Ala His Cys Phe Arg 35 40 45 Asn Thr Ser Glu Thr Ser Leu Tyr Gln Val Leu Leu Gly Ala Arg Gln 50 55 60 Leu Val Gln Pro Gly Pro His Ala Met Tyr Ala Arg Val Arg Gln Val 65 70 75 80 Glu Ser Asn Pro Leu Tyr Gln Gly Thr Ala Ser Ser Ala Asp Val Ala 85 90 95 Leu Val Glu Leu Glu Ala Pro Val Pro Phe Thr Asn Tyr Ile Leu Pro 100 105 110 Val Cys Leu Pro Asp Pro Ser Val Ile Phe Glu Thr Gly Met Asn Cys 115 120 125 Trp Val Thr Gly Trp Gly Ser Pro Ser Glu Glu Asp Leu Leu Pro Glu 130 135 140 Pro Arg Ile Leu Gln Lys Leu Ala Val Pro Ile Ile Asp Thr Pro Lys 145 150 155 160 Cys Asn Leu Leu Tyr Ser Lys Asp Thr Glu Phe Gly Tyr Gln Pro Lys 165 170 175 Thr Ile Lys Asn Asp Met Leu Cys Ala Gly Phe Glu

Glu Gly Lys Lys 180 185 190 Asp Ala Cys Lys Gly Asp Ser Gly Gly Pro Leu Val Cys Leu Val Gly 195 200 205 Gln Ser Trp Leu Gln Ala Gly Val Ile Ser Trp Gly Glu Gly Cys Ala 210 215 220 Arg Gln Asn Arg Pro Gly Val Tyr Ile Arg Val Thr Ala His His Asn 225 230 235 240 Trp Ile His Arg Ile Ile Pro Lys Leu Gln Phe Gln Pro Ala Arg Leu 245 250 255 Gly Gly Gln Lys 260 22 783 DNA Homo sapiens CDS (1)...(783) 22 atg ctg aac cga atg gtg ggc ggg cag gac acg cag gag ggc gag tgg 48 Met Leu Asn Arg Met Val Gly Gly Gln Asp Thr Gln Glu Gly Glu Trp 1 5 10 15 ccc tgg caa gtc agc atc cag cgc aac gga agc cac ttc tgc ggg ggc 96 Pro Trp Gln Val Ser Ile Gln Arg Asn Gly Ser His Phe Cys Gly Gly 20 25 30 agc ctc atc gcg gag cag tgg gtc ctg acg gct gcg cac tgc ttc cgc 144 Ser Leu Ile Ala Glu Gln Trp Val Leu Thr Ala Ala His Cys Phe Arg 35 40 45 aac acc tct gag acg tcc ctg tac cag gtc ctg ctg ggg gca agg cag 192 Asn Thr Ser Glu Thr Ser Leu Tyr Gln Val Leu Leu Gly Ala Arg Gln 50 55 60 cta gtg cag ccg gga cca cac gct atg tat gcc cgg gtg agg cag gtg 240 Leu Val Gln Pro Gly Pro His Ala Met Tyr Ala Arg Val Arg Gln Val 65 70 75 80 gag agc aac ccc ctg tac cag ggc acg gcc tcc agc gct gac gtg gcc 288 Glu Ser Asn Pro Leu Tyr Gln Gly Thr Ala Ser Ser Ala Asp Val Ala 85 90 95 ctg gtg gag ctg gag gca cca gtg ccc ttc acc aat tac atc ctc ccc 336 Leu Val Glu Leu Glu Ala Pro Val Pro Phe Thr Asn Tyr Ile Leu Pro 100 105 110 gtg tgc ctg cct gac ccc tcg gtg atc ttt gag acg ggc atg aac tgc 384 Val Cys Leu Pro Asp Pro Ser Val Ile Phe Glu Thr Gly Met Asn Cys 115 120 125 tgg gtc act ggc tgg ggc agc ccc agt gag gaa gac ctc ctg ccc gaa 432 Trp Val Thr Gly Trp Gly Ser Pro Ser Glu Glu Asp Leu Leu Pro Glu 130 135 140 ccg cgg atc ctg cag aaa ctc gct gtg ccc atc atc gac aca ccc aag 480 Pro Arg Ile Leu Gln Lys Leu Ala Val Pro Ile Ile Asp Thr Pro Lys 145 150 155 160 tgc aac ctg ctc tac agc aaa gac acc gag ttt ggc tac caa ccc aaa 528 Cys Asn Leu Leu Tyr Ser Lys Asp Thr Glu Phe Gly Tyr Gln Pro Lys 165 170 175 acc atc aag aat gac atg ctg tgc gcc ggc ttc gag gag ggc aag aag 576 Thr Ile Lys Asn Asp Met Leu Cys Ala Gly Phe Glu Glu Gly Lys Lys 180 185 190 gat gcc tgc aag ggc gac tcg ggc ggc ccc ctg gtg tgc ctc gtg ggt 624 Asp Ala Cys Lys Gly Asp Ser Gly Gly Pro Leu Val Cys Leu Val Gly 195 200 205 cag tcg tgg ctg cag gcg ggg gtg atc agc tgg ggt gag ggc tgt gcc 672 Gln Ser Trp Leu Gln Ala Gly Val Ile Ser Trp Gly Glu Gly Cys Ala 210 215 220 cgc cag aac cgc cca ggt gtc tac atc cgt gtc acc gcc cac cac aac 720 Arg Gln Asn Arg Pro Gly Val Tyr Ile Arg Val Thr Ala His His Asn 225 230 235 240 tgg atc cat cgg atc atc ccc aaa ctg cag ttc cag cca gcg agg ttg 768 Trp Ile His Arg Ile Ile Pro Lys Leu Gln Phe Gln Pro Ala Arg Leu 245 250 255 ggc ggc cag aag tga 783 Gly Gly Gln Lys * 260 23 271 PRT Artificial Sequence Consensus amino acid sequence of trypsin-like domain VARIANT (21)...(26) Xaa = Any Amino Acid VARIANT (44)...(53) Xaa = Any Amino Acid VARIANT (96)...(100) Xaa = Any Amino Acid VARIANT (184)...(202) Xaa = Any Amino Acid VARIANT (231)...(236) Xaa = Any Amino Acid 23 Arg Ile Val Gly Gly Ser Glu Ala Lys Ile Gly Ser Phe Pro Trp Gln 1 5 10 15 Val Ser Leu Gln Xaa Xaa Xaa Xaa Xaa Xaa Cys Gly Gly Ser Leu Ile 20 25 30 Ser Pro Arg Trp Val Leu Thr Ala Ala His Cys Xaa Xaa Xaa Xaa Xaa 35 40 45 Xaa Xaa Xaa Xaa Xaa Arg Val Arg Leu Gly Ser His Asp Leu Ser Ser 50 55 60 Gly Glu Glu Thr Glu Gly Gly Pro Arg Leu Asp Ser Pro Gly Gly Gln 65 70 75 80 Val Ile Lys Val Ser Lys Ile Ile Glu Val His Pro Asn Tyr Asn Xaa 85 90 95 Xaa Xaa Xaa Xaa Asn Asp Ile Ala Leu Leu Lys Leu Lys Glu Pro Val 100 105 110 Thr Leu Ser Asp Ser Asn Thr Val Arg Pro Ile Cys Leu Pro Ser Ser 115 120 125 Asn Glu Ile Lys Thr Ser Glu Gly Asn Thr Val Pro Ala Gly Thr Thr 130 135 140 Cys Thr Val Ser Gly Trp Gly Arg Thr Ser Glu Gly Pro Glu Glu Ser 145 150 155 160 Gly Gly Gly Ser Leu Pro Asp Val Leu Gln Glu Val Asn Val Pro Ile 165 170 175 Val Ser Asn Glu Thr Cys Arg Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 180 185 190 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Met Leu Cys Ala Gly Tyr 195 200 205 Leu Glu Gly Gly Asn Thr Pro Gly Gly Lys Asp Ala Cys Gln Gly Asp 210 215 220 Gly Gly Pro Leu Val Cys Xaa Xaa Xaa Xaa Xaa Xaa Val Leu Val Gly 225 230 235 240 Ile Val Ser Trp Gly Ser Ser Ser Leu Tyr Gly Cys Ala Arg Pro Asn 245 250 255 Lys Pro Gly Val Tyr Thr Arg Val Ser Ser Tyr Leu Asp Trp Ile 260 265 270 24 7 PRT Artificial Sequence Consensus amino acid sequence 24 Gly Asp Ser Gly Gly Pro Leu 1 5 25 7220 DNA Homo sapiens CDS (129)...(2900) 25 agcggcgagc cgcgaaccag gcagtccggg gcatccagac tgcaggccgc gcccaggccg 60 cgcccaggct gcgccgcccg cctgcctccc gcgctgccgc gtcgccagtg ctagcgctcc 120 tctccagc atg ctg cgg cgg ggc agc cag gcg ctc cgg cgc ttc tcc act 170 Met Leu Arg Arg Gly Ser Gln Ala Leu Arg Arg Phe Ser Thr 1 5 10 ggc cgg gtt tat ttc aaa aac aag ctg aag ttg gca cta att ggc cag 218 Gly Arg Val Tyr Phe Lys Asn Lys Leu Lys Leu Ala Leu Ile Gly Gln 15 20 25 30 agc ctc ttt gga caa gaa gtc tat agc cac ctc cgc aaa gag ggc cac 266 Ser Leu Phe Gly Gln Glu Val Tyr Ser His Leu Arg Lys Glu Gly His 35 40 45 cga gta gta ggg gtg ttc aca gtt cca gac aag gat gga aaa gct gac 314 Arg Val Val Gly Val Phe Thr Val Pro Asp Lys Asp Gly Lys Ala Asp 50 55 60 cct ctg gct ttg gct gca gag aaa gat ggg acc cct gtg ttc aag ctt 362 Pro Leu Ala Leu Ala Ala Glu Lys Asp Gly Thr Pro Val Phe Lys Leu 65 70 75 cct aaa tgg agg gtc aag ggc aag acc atc aaa gaa gtg gca gaa gcc 410 Pro Lys Trp Arg Val Lys Gly Lys Thr Ile Lys Glu Val Ala Glu Ala 80 85 90 tac aga tcc gtg ggt gca gag cta aat gtg ctc cct ttc tgc act cag 458 Tyr Arg Ser Val Gly Ala Glu Leu Asn Val Leu Pro Phe Cys Thr Gln 95 100 105 110 ttc att ccc atg gat ata att gat agt cca aag cac ggc tct atc att 506 Phe Ile Pro Met Asp Ile Ile Asp Ser Pro Lys His Gly Ser Ile Ile 115 120 125 tat cac cca tcc atc ctg ccc agg cac aga gga gcc tct gct atc aat 554 Tyr His Pro Ser Ile Leu Pro Arg His Arg Gly Ala Ser Ala Ile Asn 130 135 140 tgg act cta att atg gga gat aag aaa gct ggg ttt tct gtt ttc tgg 602 Trp Thr Leu Ile Met Gly Asp Lys Lys Ala Gly Phe Ser Val Phe Trp 145 150 155 gct gat gat ggc ttg gat aca gga ccc atc ctt ctt cag aga tca tgt 650 Ala Asp Asp Gly Leu Asp Thr Gly Pro Ile Leu Leu Gln Arg Ser Cys 160 165 170 gat gtt gaa ccc aat gat aca gtg gat gca ctt tat aat cgg ttt ctt 698 Asp Val Glu Pro Asn Asp Thr Val Asp Ala Leu Tyr Asn Arg Phe Leu 175 180 185 190 ttt cct gaa gga atc aag gcc atg gta gaa gct gtc caa ctc ata gct 746 Phe Pro Glu Gly Ile Lys Ala Met Val Glu Ala Val Gln Leu Ile Ala 195 200 205 gat gga aaa gct cct cgt ata ccc cag cca gaa gaa ggg gca aca tat 794 Asp Gly Lys Ala Pro Arg Ile Pro Gln Pro Glu Glu Gly Ala Thr Tyr 210 215 220 gaa ggt atc cag aaa aag gaa aat gct gag att tct tgg gac cag tct 842 Glu Gly Ile Gln Lys Lys Glu Asn Ala Glu Ile Ser Trp Asp Gln Ser 225 230 235 gcc gaa gtt tta cat aac tgg att cga ggt cat gat aaa gtc cct gga 890 Ala Glu Val Leu His Asn Trp Ile Arg Gly His Asp Lys Val Pro Gly 240 245 250 gct tgg aca gag ata aat gga cag atg gtc act ttc tat ggc tcg aca 938 Ala Trp Thr Glu Ile Asn Gly Gln Met Val Thr Phe Tyr Gly Ser Thr 255 260 265 270 tta ctg aat agc tct gtg cct cct gga gaa cca ctg gaa att aaa ggt 986 Leu Leu Asn Ser Ser Val Pro Pro Gly Glu Pro Leu Glu Ile Lys Gly 275 280 285 gcc aag aag cct ggt ctc gtt acc aaa aat gga ctt gtt ctt ttt ggt 1034 Ala Lys Lys Pro Gly Leu Val Thr Lys Asn Gly Leu Val Leu Phe Gly 290 295 300 aac gat gga aaa gca ctg acg gtg aga aat ctg cag ttt gaa gat gga 1082 Asn Asp Gly Lys Ala Leu Thr Val Arg Asn Leu Gln Phe Glu Asp Gly 305 310 315 aaa atg atc cct gcc tct cag tac ttt tca acg ggt gag acg tca gtg 1130 Lys Met Ile Pro Ala Ser Gln Tyr Phe Ser Thr Gly Glu Thr Ser Val 320 325 330 gta gaa ctg aca gct gaa gag gtg aaa gtg gca gag acc atc aag gtc 1178 Val Glu Leu Thr Ala Glu Glu Val Lys Val Ala Glu Thr Ile Lys Val 335 340 345 350 atc tgg gct gga att tta agc aat gtc ccc att att gaa gac tca aca 1226 Ile Trp Ala Gly Ile Leu Ser Asn Val Pro Ile Ile Glu Asp Ser Thr 355 360 365 gac ttc ttt aaa tct gga gca agc tca atg gat gtt gcc agg ctg gtt 1274 Asp Phe Phe Lys Ser Gly Ala Ser Ser Met Asp Val Ala Arg Leu Val 370 375 380 gaa gag atc aga cag aaa tgt ggt ggg ctt cag ttg cag aat gaa gat 1322 Glu Glu Ile Arg Gln Lys Cys Gly Gly Leu Gln Leu Gln Asn Glu Asp 385 390 395 gtc tat atg gcc acc aag ttt gaa ggc ttt atc caa aag gtc gtg agg 1370 Val Tyr Met Ala Thr Lys Phe Glu Gly Phe Ile Gln Lys Val Val Arg 400 405 410 aaa ctg aga gga gaa gat caa gag gtg gag ctg gtt gta gat tat att 1418 Lys Leu Arg Gly Glu Asp Gln Glu Val Glu Leu Val Val Asp Tyr Ile 415 420 425 430 tca aag gag gtc aat gaa atc atg gta aaa atg cca tac cag tgt ttc 1466 Ser Lys Glu Val Asn Glu Ile Met Val Lys Met Pro Tyr Gln Cys Phe 435 440 445 ata aat gga cag ttc aca gat gca gac gat gga aag act tac gac act 1514 Ile Asn Gly Gln Phe Thr Asp Ala Asp Asp Gly Lys Thr Tyr Asp Thr 450 455 460 atc aac cca aca gat gga tct aca ata tgc aaa gta tcc tac gct tct 1562 Ile Asn Pro Thr Asp Gly Ser Thr Ile Cys Lys Val Ser Tyr Ala Ser 465 470 475 ttg gcg gat gtt gat aaa gca gta gca gca gca aaa gat gct ttt gaa 1610 Leu Ala Asp Val Asp Lys Ala Val Ala Ala Ala Lys Asp Ala Phe Glu 480 485 490 aac ggt gaa tgg gga aga atg aat gca aga gaa aga gga aga ttg atg 1658 Asn Gly Glu Trp Gly Arg Met Asn Ala Arg Glu Arg Gly Arg Leu Met 495 500 505 510 tat aga ctt gca gac cta ctg gaa gag aac caa gaa gag ctg gca act 1706 Tyr Arg Leu Ala Asp Leu Leu Glu Glu Asn Gln Glu Glu Leu Ala Thr 515 520 525 att gaa gcc ctt gat tca ggg gct gtc tat acc ttg gcc ctg aag aca 1754 Ile Glu Ala Leu Asp Ser Gly Ala Val Tyr Thr Leu Ala Leu Lys Thr 530 535 540 cac att gga atg tct gtg caa aca ttc aga tat ttt gct ggc tgg tgc 1802 His Ile Gly Met Ser Val Gln Thr Phe Arg Tyr Phe Ala Gly Trp Cys 545 550 555 gac aaa att cag ggt tct act att cca atc aac cag gcc cgt cca aat 1850 Asp Lys Ile Gln Gly Ser Thr Ile Pro Ile Asn Gln Ala Arg Pro Asn 560 565 570 cgc aat ctg acc ttc acc aag aaa gag cca ctc ggt gtc tgt gcc att 1898 Arg Asn Leu Thr Phe Thr Lys Lys Glu Pro Leu Gly Val Cys Ala Ile 575 580 585 590 att att ccc tgg aac tac ccg ctg atg atg ctg gca tgg aag agt gct 1946 Ile Ile Pro Trp Asn Tyr Pro Leu Met Met Leu Ala Trp Lys Ser Ala 595 600 605 gcg tgt ttg gca gca ggc aat acc tta gtg ctc aag cca gca cag gtc 1994 Ala Cys Leu Ala Ala Gly Asn Thr Leu Val Leu Lys Pro Ala Gln Val 610 615 620 acg ccc ttg act gct ttg aag ttt gca gaa ctg tct gtg aaa gca ggc 2042 Thr Pro Leu Thr Ala Leu Lys Phe Ala Glu Leu Ser Val Lys Ala Gly 625 630 635 ttt cca aag ggg gtc atc aac atc att cca ggc tca ggt ggc ata gca 2090 Phe Pro Lys Gly Val Ile Asn Ile Ile Pro Gly Ser Gly Gly Ile Ala 640 645 650 gga caa cgt ctg tct gaa cat cct gac atc cgc aaa ctt ggt ttc act 2138 Gly Gln Arg Leu Ser Glu His Pro Asp Ile Arg Lys Leu Gly Phe Thr 655 660 665 670 gga tcc act cct att ggc aaa cag atc atg aag agc tgt gct gtt agc 2186 Gly Ser Thr Pro Ile Gly Lys Gln Ile Met Lys Ser Cys Ala Val Ser 675 680 685 aac ttg aag aaa gtt tcc ctt gag ctt ggt ggc aag tct cca ctt ata 2234 Asn Leu Lys Lys Val Ser Leu Glu Leu Gly Gly Lys Ser Pro Leu Ile 690 695 700 ata ttt aat gac tgt gaa ctt gac aag gct gtg cga atg ggc atg gga 2282 Ile Phe Asn Asp Cys Glu Leu Asp Lys Ala Val Arg Met Gly Met Gly 705 710 715 gca gta ttt ttc aac aaa gga gag aac tgt att gct gct ggg cgg ttg 2330 Ala Val Phe Phe Asn Lys Gly Glu Asn Cys Ile Ala Ala Gly Arg Leu 720 725 730 ttc gtg gaa gaa tcc atc cac gac gaa ttt gtg aca aga gtg gta gaa 2378 Phe Val Glu Glu Ser Ile His Asp Glu Phe Val Thr Arg Val Val Glu 735 740 745 750 gaa att aaa aag atg aaa att ggt gat cca ctt gac aga tcc act gat 2426 Glu Ile Lys Lys Met Lys Ile Gly Asp Pro Leu Asp Arg Ser Thr Asp 755 760 765 cat ggg ccc caa aat cat aag gct cat ctg gaa aag ctg ctg caa tac 2474 His Gly Pro Gln Asn His Lys Ala His Leu Glu Lys Leu Leu Gln Tyr 770 775 780 tgt gaa act gga gtg aaa gaa ggg gcc act ttg gtg tac ggg gga aga 2522 Cys Glu Thr Gly Val Lys Glu Gly Ala Thr Leu Val Tyr Gly Gly Arg 785 790 795 caa gtc caa agg cca ggc ttt ttc atg gag ccg acc gtg ttc aca gat 2570 Gln Val Gln Arg Pro Gly Phe Phe Met Glu Pro Thr Val Phe Thr Asp 800 805 810 gtg gaa gac tac atg tac ctc gcc aaa gag gaa tcc ttt ggg cct att 2618 Val Glu Asp Tyr Met Tyr Leu Ala Lys Glu Glu Ser Phe Gly Pro Ile 815 820 825 830 atg gtc att tct aaa ttc caa aat ggg gac atc gat gga gtg ttg cag 2666 Met Val Ile Ser Lys Phe Gln Asn Gly Asp Ile Asp Gly Val Leu Gln 835 840 845 cga gca aat agt aca gag tat ggt ttg gcc tca ggg gtt ttt aca aga 2714 Arg Ala Asn Ser Thr Glu Tyr Gly Leu Ala Ser Gly Val Phe Thr Arg 850 855 860 gac ata aac aaa gct atg tat gtg agt gaa aaa ctg gaa gca gga act 2762 Asp Ile Asn Lys Ala Met Tyr Val Ser Glu Lys Leu Glu Ala Gly Thr 865 870 875 gtt ttt att aac aca tac aac aag aca gat gtg gcg gcc cca ttt ggc 2810 Val Phe Ile Asn Thr Tyr Asn Lys Thr Asp Val Ala Ala Pro Phe Gly 880 885 890 gga gtt aaa caa tct ggc ttt gga aaa gac tta ggt gag gaa gct cta 2858 Gly Val Lys Gln Ser Gly Phe Gly Lys Asp Leu Gly Glu Glu Ala Leu 895 900 905 910 aat gaa tat ctc aaa acc aag acg gtg aca ctg gaa tat tag 2900 Asn Glu Tyr Leu Lys Thr Lys Thr Val Thr Leu Glu Tyr * 915 920 agcaacacca tcatcaggaa agccttgaca gacagccctt tacaactctg gacacactta 2960 agaagattgg gtgtgttgag gcaggaggtg tcagccacaa accaaaaaat acacagatgg 3020 accatgaaga gggccaggcc atgttaaagc atttacacat gtgcctgagt attttctaat 3080 acaccttcca gtgatttgga gttgttgcat tttgactatg ttgtatatca tacgtatttc 3140 taaaatacca agctgtttct cccctaccta gacaaatcta ttcatggttc ccatcttgaa 3200 gatgtcagta ccatgcagtt ataatacaca aggtgcattt attggaaact ttgtataata 3260 tgtacaggtt tttaacctct gaactataca tagggggtta ttaaaaagat tttctataag 3320 tcttctaagg aacagtataa cctgtaagga atgtgaaggt agttcttttt tagtatttgg 3380 aaataagata catctttgtg cctttgatat tccatttttt aacccactgt gatgggtgat 3440 caacctagaa acattatctt gagtacctac

taggtaccag gtactatatt atgttctgag 3500 gagtatagag aatttaatga tatgatggct ggcccccaca tagtttaaat tttagtaaat 3560 agcttttgaa gcaaatttta catatgatat agtagaaggc tgatccctgg tcgtatcata 3620 ccatcttcct atctatgtaa ctttgggaaa ctctcgcaac tcctctgagc ctctgcttcc 3680 ctatgtgtaa aacagggata gtaaatgcct tcctcaggac ccttaatagg agaattcatt 3740 gcagtaatgt aagtaaagca cctcacatta atgctttgct catggtaagt actcaaattt 3800 aactctgatt tcctccgtca ccattcttaa aagatattga gatagtttaa ttaactagat 3860 gaattcattt cccacaaccc ttttcaatca tcaattccta gatatttttc tcatccattg 3920 ttctgacaca atgcctgata cagcagcact gaaaaatgcc acacaatgaa aaatggcaat 3980 agtacaagga aaaggggtgc ttttctttgg gcagctcgct cgtccttcat gggacatctt 4040 actttccatt tttctaccta ttggttctgc tgttcactgg ctgtgtgatc ttgggcaaga 4100 tagtaatcta atatctcaga gcctaggttg agtatctata aaatgaaaat caaatctcta 4160 tctcagtagg tgttgcaagg attcagtgag ataatataca taatgcactt aacaaggcgt 4220 ttggaccata gcattgaaga aatggaaact attaacagcc catttcccat tggcagacag 4280 aagtagtcag gtgagtaaat tttcaccatc tatgtgtgac tagaaggcgg caaatttctg 4340 aatcacatga gtctccaaaa gatagccaga aagttaaatt ctattaatcc tcctttaaaa 4400 ataaaatttc agtaaacatt cctttttctt tggctttgaa gaagccttag ggaatatttg 4460 tcattttgga gacttggcag aataacatga ggggattgta gggaatcaat aaaaactaaa 4520 caacaaaatc agagtcagag aacattttca aaaggaagaa taggaggttt gatcccagca 4580 tgataaacag agcgaatttg gcctggaagc acttttgatt atactatagc tcatttacca 4640 tcccagagtt tggcacagct gaaattttaa gttggaatga atattcactg ggcccaaaat 4700 gacagttcat atttgaataa aagtgacaaa agccttttta taagtaatca cttttaagtg 4760 aaatgtttta actgatttca tgtgatttag aatatgattt aatcaaatta ttttaatgat 4820 agatggaatg gcagacaaaa acatgcctgt ccttctagac tgattttact ttaccctcta 4880 atattcatct cagtagcagt gttttaaata ttctctgggc tgcaaaactc tttgggaatc 4940 tgataaaagc tatgaacact ccctgtgtcc cgcttctacc cccaaaattc atgtgcacac 5000 acacaattct gcaagtatct tcaaagggtt cacagacctc ccaaaggcca tgcttgggcc 5060 ccagattaag aactcctttc tccatagcaa gttttaaaca tttcttacca gcttacattt 5120 ttagatctgg ctgatcagaa tcaaaggctc tgtgtaatac ataaagttac caagtgaact 5180 ggaattggaa catcaccctc cccagcctgc taggtgattt acttaacaca tagagtaata 5240 aaatcatcgc tgttgcttta gatcacggat tattttgcta ataatgctaa ggatgaagct 5300 gtgatcttat tatcacctga atcgggaggt gtggacactt taagcagttc cactttcctt 5360 ctaattcccc atccccatgc ctttgctaaa gctgtccctt ttgctctaac acccttcctg 5420 gaccttccta ccctagctgg gctaagtgtt tctcctcagc gttcccactt gtttcaaaca 5480 tagcacttac cacttgtact aaaattactt gccttcttaa ttagatatga acaaccctcc 5540 ccaactccag tatgggcctt ctgtcaataa taatacgata tgacagctac catttattaa 5600 gggcctcctg tatgaaagac cttaggctaa gcatgtttta aatgttattt aatcttcaca 5660 atctctgaaa aaaatgaaga aatcaacgtg cttttcttac tacctctacc cctaagccat 5720 tattactttt tttttttttt tgagacagag ttttgctctt gttgcccagg ctgcagtgca 5780 gtggtgcaat cttggctcac tgcaacctct gcctcttggg ttcaagcgat tgtcatgcct 5840 tagccttcca agtagctggg attacaggtg tgtgccacta cacctggcta agtagagatg 5900 gggtttcgcc atgttggcca ggctggtctt gaactcctga cctcaagtga tccacctgcc 5960 tccgcctccc aaagtgctgg gattacaggc atgaaccact gcacctggcc tgttacctct 6020 ttcctacaat tttgctcaag tctcccaact ggtcttctgg attcctctct tctgcggtcc 6080 tgttcaaagc ttaagtcaga cagtgtcact tcactcgtct gtttaaaacc tttcaatggc 6140 ccccatttca cgtagaccaa agtccaacgt atttacctgg cctactgatc ttgctcctag 6200 ctacctctga cctcatctcc tgtcaatttc cctctcattc tgttccacca tcctgactgc 6260 cttgacttcc tcaacagaac aagcctgctc ctgcctcagg gcctctgtcc ttattcttcc 6320 tcttcccagg ggtgtgctgg taaaatattt aacaaatagt tctccgggac gggggagaaa 6380 accctcattt gtagcatttg caggtatcta tgtgtaaata ctctcatcaa ggctattttt 6440 gagccactaa tttgccttca ctgaatacag agtttgggaa gagatgcatg ccatcagaac 6500 aaatgcaagc cagcaccagc acaccactgc ctcttcctgc aactcttgtc catacacaac 6560 ctcatggctg gctggctcac ttcctgcagg tctctcctca aatatcatct gatgagagac 6620 acattccctg actatgcttt ctaaaatagg ccatatgccc ccacattcat accccatctg 6680 ctgtcattct ttattctttt tataagtgca ttattttcat agcacttatc actacctgtt 6740 gtatattaat caatgatctt ttcccattag aatgtaagtt tcatgaacag gtacttgttt 6800 taatactgta tctccagtcc taatgtgtaa caggagccca ataaatgttt gctttcaaat 6860 ggagaggtta agtaacctgc tcaaatcaca cagctattaa gtggcagaac aggttttcaa 6920 gcaatgcatc tggtggtttt aactaagtcg agatagtttt tattcctaat gcctaaatca 6980 gggcctaggt agtgagctgt gggcacatat taagtattgg ttaaactaaa aataataagc 7040 aaaatggaca ttatctataa aagcttttgt ggaaatggct agagctaggg taaggaaaca 7100 aatttggttc cccatacctg cccttcaaga aaataaagct gtcaaggaaa attgggctaa 7160 gagtaggata tgagggatga tggataaggc atgagacatg agaaaataag ggggattaaa 7220 26 923 PRT Homo sapiens 26 Met Leu Arg Arg Gly Ser Gln Ala Leu Arg Arg Phe Ser Thr Gly Arg 1 5 10 15 Val Tyr Phe Lys Asn Lys Leu Lys Leu Ala Leu Ile Gly Gln Ser Leu 20 25 30 Phe Gly Gln Glu Val Tyr Ser His Leu Arg Lys Glu Gly His Arg Val 35 40 45 Val Gly Val Phe Thr Val Pro Asp Lys Asp Gly Lys Ala Asp Pro Leu 50 55 60 Ala Leu Ala Ala Glu Lys Asp Gly Thr Pro Val Phe Lys Leu Pro Lys 65 70 75 80 Trp Arg Val Lys Gly Lys Thr Ile Lys Glu Val Ala Glu Ala Tyr Arg 85 90 95 Ser Val Gly Ala Glu Leu Asn Val Leu Pro Phe Cys Thr Gln Phe Ile 100 105 110 Pro Met Asp Ile Ile Asp Ser Pro Lys His Gly Ser Ile Ile Tyr His 115 120 125 Pro Ser Ile Leu Pro Arg His Arg Gly Ala Ser Ala Ile Asn Trp Thr 130 135 140 Leu Ile Met Gly Asp Lys Lys Ala Gly Phe Ser Val Phe Trp Ala Asp 145 150 155 160 Asp Gly Leu Asp Thr Gly Pro Ile Leu Leu Gln Arg Ser Cys Asp Val 165 170 175 Glu Pro Asn Asp Thr Val Asp Ala Leu Tyr Asn Arg Phe Leu Phe Pro 180 185 190 Glu Gly Ile Lys Ala Met Val Glu Ala Val Gln Leu Ile Ala Asp Gly 195 200 205 Lys Ala Pro Arg Ile Pro Gln Pro Glu Glu Gly Ala Thr Tyr Glu Gly 210 215 220 Ile Gln Lys Lys Glu Asn Ala Glu Ile Ser Trp Asp Gln Ser Ala Glu 225 230 235 240 Val Leu His Asn Trp Ile Arg Gly His Asp Lys Val Pro Gly Ala Trp 245 250 255 Thr Glu Ile Asn Gly Gln Met Val Thr Phe Tyr Gly Ser Thr Leu Leu 260 265 270 Asn Ser Ser Val Pro Pro Gly Glu Pro Leu Glu Ile Lys Gly Ala Lys 275 280 285 Lys Pro Gly Leu Val Thr Lys Asn Gly Leu Val Leu Phe Gly Asn Asp 290 295 300 Gly Lys Ala Leu Thr Val Arg Asn Leu Gln Phe Glu Asp Gly Lys Met 305 310 315 320 Ile Pro Ala Ser Gln Tyr Phe Ser Thr Gly Glu Thr Ser Val Val Glu 325 330 335 Leu Thr Ala Glu Glu Val Lys Val Ala Glu Thr Ile Lys Val Ile Trp 340 345 350 Ala Gly Ile Leu Ser Asn Val Pro Ile Ile Glu Asp Ser Thr Asp Phe 355 360 365 Phe Lys Ser Gly Ala Ser Ser Met Asp Val Ala Arg Leu Val Glu Glu 370 375 380 Ile Arg Gln Lys Cys Gly Gly Leu Gln Leu Gln Asn Glu Asp Val Tyr 385 390 395 400 Met Ala Thr Lys Phe Glu Gly Phe Ile Gln Lys Val Val Arg Lys Leu 405 410 415 Arg Gly Glu Asp Gln Glu Val Glu Leu Val Val Asp Tyr Ile Ser Lys 420 425 430 Glu Val Asn Glu Ile Met Val Lys Met Pro Tyr Gln Cys Phe Ile Asn 435 440 445 Gly Gln Phe Thr Asp Ala Asp Asp Gly Lys Thr Tyr Asp Thr Ile Asn 450 455 460 Pro Thr Asp Gly Ser Thr Ile Cys Lys Val Ser Tyr Ala Ser Leu Ala 465 470 475 480 Asp Val Asp Lys Ala Val Ala Ala Ala Lys Asp Ala Phe Glu Asn Gly 485 490 495 Glu Trp Gly Arg Met Asn Ala Arg Glu Arg Gly Arg Leu Met Tyr Arg 500 505 510 Leu Ala Asp Leu Leu Glu Glu Asn Gln Glu Glu Leu Ala Thr Ile Glu 515 520 525 Ala Leu Asp Ser Gly Ala Val Tyr Thr Leu Ala Leu Lys Thr His Ile 530 535 540 Gly Met Ser Val Gln Thr Phe Arg Tyr Phe Ala Gly Trp Cys Asp Lys 545 550 555 560 Ile Gln Gly Ser Thr Ile Pro Ile Asn Gln Ala Arg Pro Asn Arg Asn 565 570 575 Leu Thr Phe Thr Lys Lys Glu Pro Leu Gly Val Cys Ala Ile Ile Ile 580 585 590 Pro Trp Asn Tyr Pro Leu Met Met Leu Ala Trp Lys Ser Ala Ala Cys 595 600 605 Leu Ala Ala Gly Asn Thr Leu Val Leu Lys Pro Ala Gln Val Thr Pro 610 615 620 Leu Thr Ala Leu Lys Phe Ala Glu Leu Ser Val Lys Ala Gly Phe Pro 625 630 635 640 Lys Gly Val Ile Asn Ile Ile Pro Gly Ser Gly Gly Ile Ala Gly Gln 645 650 655 Arg Leu Ser Glu His Pro Asp Ile Arg Lys Leu Gly Phe Thr Gly Ser 660 665 670 Thr Pro Ile Gly Lys Gln Ile Met Lys Ser Cys Ala Val Ser Asn Leu 675 680 685 Lys Lys Val Ser Leu Glu Leu Gly Gly Lys Ser Pro Leu Ile Ile Phe 690 695 700 Asn Asp Cys Glu Leu Asp Lys Ala Val Arg Met Gly Met Gly Ala Val 705 710 715 720 Phe Phe Asn Lys Gly Glu Asn Cys Ile Ala Ala Gly Arg Leu Phe Val 725 730 735 Glu Glu Ser Ile His Asp Glu Phe Val Thr Arg Val Val Glu Glu Ile 740 745 750 Lys Lys Met Lys Ile Gly Asp Pro Leu Asp Arg Ser Thr Asp His Gly 755 760 765 Pro Gln Asn His Lys Ala His Leu Glu Lys Leu Leu Gln Tyr Cys Glu 770 775 780 Thr Gly Val Lys Glu Gly Ala Thr Leu Val Tyr Gly Gly Arg Gln Val 785 790 795 800 Gln Arg Pro Gly Phe Phe Met Glu Pro Thr Val Phe Thr Asp Val Glu 805 810 815 Asp Tyr Met Tyr Leu Ala Lys Glu Glu Ser Phe Gly Pro Ile Met Val 820 825 830 Ile Ser Lys Phe Gln Asn Gly Asp Ile Asp Gly Val Leu Gln Arg Ala 835 840 845 Asn Ser Thr Glu Tyr Gly Leu Ala Ser Gly Val Phe Thr Arg Asp Ile 850 855 860 Asn Lys Ala Met Tyr Val Ser Glu Lys Leu Glu Ala Gly Thr Val Phe 865 870 875 880 Ile Asn Thr Tyr Asn Lys Thr Asp Val Ala Ala Pro Phe Gly Gly Val 885 890 895 Lys Gln Ser Gly Phe Gly Lys Asp Leu Gly Glu Glu Ala Leu Asn Glu 900 905 910 Tyr Leu Lys Thr Lys Thr Val Thr Leu Glu Tyr 915 920 27 2772 DNA Homo sapiens CDS (1)...(2772) 27 atg ctg cgg cgg ggc agc cag gcg ctc cgg cgc ttc tcc act ggc cgg 48 Met Leu Arg Arg Gly Ser Gln Ala Leu Arg Arg Phe Ser Thr Gly Arg 1 5 10 15 gtt tat ttc aaa aac aag ctg aag ttg gca cta att ggc cag agc ctc 96 Val Tyr Phe Lys Asn Lys Leu Lys Leu Ala Leu Ile Gly Gln Ser Leu 20 25 30 ttt gga caa gaa gtc tat agc cac ctc cgc aaa gag ggc cac cga gta 144 Phe Gly Gln Glu Val Tyr Ser His Leu Arg Lys Glu Gly His Arg Val 35 40 45 gta ggg gtg ttc aca gtt cca gac aag gat gga aaa gct gac cct ctg 192 Val Gly Val Phe Thr Val Pro Asp Lys Asp Gly Lys Ala Asp Pro Leu 50 55 60 gct ttg gct gca gag aaa gat ggg acc cct gtg ttc aag ctt cct aaa 240 Ala Leu Ala Ala Glu Lys Asp Gly Thr Pro Val Phe Lys Leu Pro Lys 65 70 75 80 tgg agg gtc aag ggc aag acc atc aaa gaa gtg gca gaa gcc tac aga 288 Trp Arg Val Lys Gly Lys Thr Ile Lys Glu Val Ala Glu Ala Tyr Arg 85 90 95 tcc gtg ggt gca gag cta aat gtg ctc cct ttc tgc act cag ttc att 336 Ser Val Gly Ala Glu Leu Asn Val Leu Pro Phe Cys Thr Gln Phe Ile 100 105 110 ccc atg gat ata att gat agt cca aag cac ggc tct atc att tat cac 384 Pro Met Asp Ile Ile Asp Ser Pro Lys His Gly Ser Ile Ile Tyr His 115 120 125 cca tcc atc ctg ccc agg cac aga gga gcc tct gct atc aat tgg act 432 Pro Ser Ile Leu Pro Arg His Arg Gly Ala Ser Ala Ile Asn Trp Thr 130 135 140 cta att atg gga gat aag aaa gct ggg ttt tct gtt ttc tgg gct gat 480 Leu Ile Met Gly Asp Lys Lys Ala Gly Phe Ser Val Phe Trp Ala Asp 145 150 155 160 gat ggc ttg gat aca gga ccc atc ctt ctt cag aga tca tgt gat gtt 528 Asp Gly Leu Asp Thr Gly Pro Ile Leu Leu Gln Arg Ser Cys Asp Val 165 170 175 gaa ccc aat gat aca gtg gat gca ctt tat aat cgg ttt ctt ttt cct 576 Glu Pro Asn Asp Thr Val Asp Ala Leu Tyr Asn Arg Phe Leu Phe Pro 180 185 190 gaa gga atc aag gcc atg gta gaa gct gtc caa ctc ata gct gat gga 624 Glu Gly Ile Lys Ala Met Val Glu Ala Val Gln Leu Ile Ala Asp Gly 195 200 205 aaa gct cct cgt ata ccc cag cca gaa gaa ggg gca aca tat gaa ggt 672 Lys Ala Pro Arg Ile Pro Gln Pro Glu Glu Gly Ala Thr Tyr Glu Gly 210 215 220 atc cag aaa aag gaa aat gct gag att tct tgg gac cag tct gcc gaa 720 Ile Gln Lys Lys Glu Asn Ala Glu Ile Ser Trp Asp Gln Ser Ala Glu 225 230 235 240 gtt tta cat aac tgg att cga ggt cat gat aaa gtc cct gga gct tgg 768 Val Leu His Asn Trp Ile Arg Gly His Asp Lys Val Pro Gly Ala Trp 245 250 255 aca gag ata aat gga cag atg gtc act ttc tat ggc tcg aca tta ctg 816 Thr Glu Ile Asn Gly Gln Met Val Thr Phe Tyr Gly Ser Thr Leu Leu 260 265 270 aat agc tct gtg cct cct gga gaa cca ctg gaa att aaa ggt gcc aag 864 Asn Ser Ser Val Pro Pro Gly Glu Pro Leu Glu Ile Lys Gly Ala Lys 275 280 285 aag cct ggt ctc gtt acc aaa aat gga ctt gtt ctt ttt ggt aac gat 912 Lys Pro Gly Leu Val Thr Lys Asn Gly Leu Val Leu Phe Gly Asn Asp 290 295 300 gga aaa gca ctg acg gtg aga aat ctg cag ttt gaa gat gga aaa atg 960 Gly Lys Ala Leu Thr Val Arg Asn Leu Gln Phe Glu Asp Gly Lys Met 305 310 315 320 atc cct gcc tct cag tac ttt tca acg ggt gag acg tca gtg gta gaa 1008 Ile Pro Ala Ser Gln Tyr Phe Ser Thr Gly Glu Thr Ser Val Val Glu 325 330 335 ctg aca gct gaa gag gtg aaa gtg gca gag acc atc aag gtc atc tgg 1056 Leu Thr Ala Glu Glu Val Lys Val Ala Glu Thr Ile Lys Val Ile Trp 340 345 350 gct gga att tta agc aat gtc ccc att att gaa gac tca aca gac ttc 1104 Ala Gly Ile Leu Ser Asn Val Pro Ile Ile Glu Asp Ser Thr Asp Phe 355 360 365 ttt aaa tct gga gca agc tca atg gat gtt gcc agg ctg gtt gaa gag 1152 Phe Lys Ser Gly Ala Ser Ser Met Asp Val Ala Arg Leu Val Glu Glu 370 375 380 atc aga cag aaa tgt ggt ggg ctt cag ttg cag aat gaa gat gtc tat 1200 Ile Arg Gln Lys Cys Gly Gly Leu Gln Leu Gln Asn Glu Asp Val Tyr 385 390 395 400 atg gcc acc aag ttt gaa ggc ttt atc caa aag gtc gtg agg aaa ctg 1248 Met Ala Thr Lys Phe Glu Gly Phe Ile Gln Lys Val Val Arg Lys Leu 405 410 415 aga gga gaa gat caa gag gtg gag ctg gtt gta gat tat att tca aag 1296 Arg Gly Glu Asp Gln Glu Val Glu Leu Val Val Asp Tyr Ile Ser Lys 420 425 430 gag gtc aat gaa atc atg gta aaa atg cca tac cag tgt ttc ata aat 1344 Glu Val Asn Glu Ile Met Val Lys Met Pro Tyr Gln Cys Phe Ile Asn 435 440 445 gga cag ttc aca gat gca gac gat gga aag act tac gac act atc aac 1392 Gly Gln Phe Thr Asp Ala Asp Asp Gly Lys Thr Tyr Asp Thr Ile Asn 450 455 460 cca aca gat gga tct aca ata tgc aaa gta tcc tac gct tct ttg gcg 1440 Pro Thr Asp Gly Ser Thr Ile Cys Lys Val Ser Tyr Ala Ser Leu Ala 465 470 475 480 gat gtt gat aaa gca gta gca gca gca aaa gat gct ttt gaa aac ggt 1488 Asp Val Asp Lys Ala Val Ala Ala Ala Lys Asp Ala Phe Glu Asn Gly 485 490 495 gaa tgg gga aga atg aat gca aga gaa aga gga aga ttg atg tat aga 1536 Glu Trp Gly Arg Met Asn Ala Arg Glu Arg Gly Arg Leu Met Tyr Arg 500 505 510 ctt gca gac cta ctg gaa gag aac caa gaa gag ctg gca act att gaa 1584 Leu Ala Asp Leu Leu Glu Glu Asn Gln Glu Glu Leu Ala Thr Ile Glu 515 520 525 gcc ctt gat tca ggg gct gtc tat acc ttg gcc ctg aag aca cac att 1632 Ala Leu Asp Ser Gly Ala Val Tyr Thr Leu Ala Leu Lys Thr His Ile 530 535 540 gga atg tct gtg caa aca ttc aga tat ttt gct ggc tgg tgc gac aaa 1680 Gly Met Ser Val Gln Thr Phe Arg Tyr Phe Ala Gly Trp Cys Asp Lys 545 550 555 560 att cag ggt tct act att cca atc aac cag gcc cgt cca aat

cgc aat 1728 Ile Gln Gly Ser Thr Ile Pro Ile Asn Gln Ala Arg Pro Asn Arg Asn 565 570 575 ctg acc ttc acc aag aaa gag cca ctc ggt gtc tgt gcc att att att 1776 Leu Thr Phe Thr Lys Lys Glu Pro Leu Gly Val Cys Ala Ile Ile Ile 580 585 590 ccc tgg aac tac ccg ctg atg atg ctg gca tgg aag agt gct gcg tgt 1824 Pro Trp Asn Tyr Pro Leu Met Met Leu Ala Trp Lys Ser Ala Ala Cys 595 600 605 ttg gca gca ggc aat acc tta gtg ctc aag cca gca cag gtc acg ccc 1872 Leu Ala Ala Gly Asn Thr Leu Val Leu Lys Pro Ala Gln Val Thr Pro 610 615 620 ttg act gct ttg aag ttt gca gaa ctg tct gtg aaa gca ggc ttt cca 1920 Leu Thr Ala Leu Lys Phe Ala Glu Leu Ser Val Lys Ala Gly Phe Pro 625 630 635 640 aag ggg gtc atc aac atc att cca ggc tca ggt ggc ata gca gga caa 1968 Lys Gly Val Ile Asn Ile Ile Pro Gly Ser Gly Gly Ile Ala Gly Gln 645 650 655 cgt ctg tct gaa cat cct gac atc cgc aaa ctt ggt ttc act gga tcc 2016 Arg Leu Ser Glu His Pro Asp Ile Arg Lys Leu Gly Phe Thr Gly Ser 660 665 670 act cct att ggc aaa cag atc atg aag agc tgt gct gtt agc aac ttg 2064 Thr Pro Ile Gly Lys Gln Ile Met Lys Ser Cys Ala Val Ser Asn Leu 675 680 685 aag aaa gtt tcc ctt gag ctt ggt ggc aag tct cca ctt ata ata ttt 2112 Lys Lys Val Ser Leu Glu Leu Gly Gly Lys Ser Pro Leu Ile Ile Phe 690 695 700 aat gac tgt gaa ctt gac aag gct gtg cga atg ggc atg gga gca gta 2160 Asn Asp Cys Glu Leu Asp Lys Ala Val Arg Met Gly Met Gly Ala Val 705 710 715 720 ttt ttc aac aaa gga gag aac tgt att gct gct ggg cgg ttg ttc gtg 2208 Phe Phe Asn Lys Gly Glu Asn Cys Ile Ala Ala Gly Arg Leu Phe Val 725 730 735 gaa gaa tcc atc cac gac gaa ttt gtg aca aga gtg gta gaa gaa att 2256 Glu Glu Ser Ile His Asp Glu Phe Val Thr Arg Val Val Glu Glu Ile 740 745 750 aaa aag atg aaa att ggt gat cca ctt gac aga tcc act gat cat ggg 2304 Lys Lys Met Lys Ile Gly Asp Pro Leu Asp Arg Ser Thr Asp His Gly 755 760 765 ccc caa aat cat aag gct cat ctg gaa aag ctg ctg caa tac tgt gaa 2352 Pro Gln Asn His Lys Ala His Leu Glu Lys Leu Leu Gln Tyr Cys Glu 770 775 780 act gga gtg aaa gaa ggg gcc act ttg gtg tac ggg gga aga caa gtc 2400 Thr Gly Val Lys Glu Gly Ala Thr Leu Val Tyr Gly Gly Arg Gln Val 785 790 795 800 caa agg cca ggc ttt ttc atg gag ccg acc gtg ttc aca gat gtg gaa 2448 Gln Arg Pro Gly Phe Phe Met Glu Pro Thr Val Phe Thr Asp Val Glu 805 810 815 gac tac atg tac ctc gcc aaa gag gaa tcc ttt ggg cct att atg gtc 2496 Asp Tyr Met Tyr Leu Ala Lys Glu Glu Ser Phe Gly Pro Ile Met Val 820 825 830 att tct aaa ttc caa aat ggg gac atc gat gga gtg ttg cag cga gca 2544 Ile Ser Lys Phe Gln Asn Gly Asp Ile Asp Gly Val Leu Gln Arg Ala 835 840 845 aat agt aca gag tat ggt ttg gcc tca ggg gtt ttt aca aga gac ata 2592 Asn Ser Thr Glu Tyr Gly Leu Ala Ser Gly Val Phe Thr Arg Asp Ile 850 855 860 aac aaa gct atg tat gtg agt gaa aaa ctg gaa gca gga act gtt ttt 2640 Asn Lys Ala Met Tyr Val Ser Glu Lys Leu Glu Ala Gly Thr Val Phe 865 870 875 880 att aac aca tac aac aag aca gat gtg gcg gcc cca ttt ggc gga gtt 2688 Ile Asn Thr Tyr Asn Lys Thr Asp Val Ala Ala Pro Phe Gly Gly Val 885 890 895 aaa caa tct ggc ttt gga aaa gac tta ggt gag gaa gct cta aat gaa 2736 Lys Gln Ser Gly Phe Gly Lys Asp Leu Gly Glu Glu Ala Leu Asn Glu 900 905 910 tat ctc aaa acc aag acg gtg aca ctg gaa tat tag 2772 Tyr Leu Lys Thr Lys Thr Val Thr Leu Glu Tyr * 915 920 28 492 PRT Artificial Sequence Aldehyde dehydrogenase Pfam consensus sequence 28 Glu Trp Val Asp Ser Ala Ser Gly Lys Thr Phe Glu Val Val Asn Pro 1 5 10 15 Ala Asn Lys Gly Glu Val Ile Gly Arg Val Pro Glu Ala Thr Ala Glu 20 25 30 Asp Val Asp Ala Ala Val Lys Ala Ala Lys Glu Ala Phe Lys Ser Gly 35 40 45 Pro Trp Trp Ala Lys Val Pro Ala Ser Glu Arg Ala Arg Ile Leu Arg 50 55 60 Lys Leu Ala Asp Leu Ile Glu Glu Arg Glu Asp Glu Leu Ala Ala Leu 65 70 75 80 Glu Thr Leu Asp Leu Gly Lys Pro Leu Ala Glu Ala Lys Gly Asp Thr 85 90 95 Glu Val Gly Arg Ala Ile Asp Glu Ile Arg Tyr Tyr Ala Gly Trp Ala 100 105 110 Arg Lys Leu Met Gly Glu Arg Arg Val Ile Pro Ser Leu Ala Thr Asp 115 120 125 Gly Asp Glu Glu Leu Asn Tyr Thr Arg Arg Glu Pro Leu Gly Val Val 130 135 140 Gly Val Ile Ser Pro Trp Asn Phe Pro Leu Leu Leu Ala Leu Trp Lys 145 150 155 160 Leu Ala Pro Ala Leu Ala Ala Gly Asn Thr Val Val Leu Lys Pro Ser 165 170 175 Glu Gln Thr Pro Leu Thr Ala Leu Leu Leu Ala Glu Leu Ile Glu Glu 180 185 190 Ala Gly Ala Asn Asn Leu Pro Lys Gly Val Val Asn Val Val Pro Gly 195 200 205 Phe Gly Ala Glu Val Gly Gln Ala Leu Leu Ser His Pro Asp Ile Asp 210 215 220 Lys Ile Ser Phe Thr Gly Ser Thr Glu Val Gly Lys Leu Ile Met Glu 225 230 235 240 Ala Ala Ala Ala Lys Asn Leu Lys Lys Val Thr Leu Glu Leu Gly Gly 245 250 255 Lys Ser Pro Val Ile Val Phe Asp Asp Ala Asp Leu Asp Lys Ala Val 260 265 270 Glu Arg Ile Val Phe Gly Ala Phe Gly Asn Ala Gly Gln Val Cys Ile 275 280 285 Ala Pro Ser Arg Leu Leu Val His Glu Ser Ile Tyr Asp Glu Phe Val 290 295 300 Glu Lys Leu Lys Glu Arg Val Lys Lys Leu Lys Leu Ile Gly Asp Pro 305 310 315 320 Leu Asp Ser Asp Thr Asn Ile Tyr Gly Pro Leu Ile Ser Glu Gln Gln 325 330 335 Phe Asp Arg Val Leu Ser Tyr Ile Glu Asp Gly Lys Glu Glu Gly Ala 340 345 350 Lys Val Leu Cys Gly Gly Glu Arg Asp Glu Ser Lys Glu Tyr Leu Gly 355 360 365 Gly Gly Tyr Tyr Val Gln Pro Thr Ile Phe Thr Asp Val Thr Pro Asp 370 375 380 Met Lys Ile Met Lys Glu Glu Ile Phe Gly Pro Val Leu Pro Ile Ile 385 390 395 400 Lys Phe Lys Asp Leu Asp Glu Ala Ile Glu Leu Ala Asn Asp Thr Glu 405 410 415 Tyr Gly Leu Ala Ala Tyr Val Phe Thr Lys Asp Ile Leu Ala Arg Ala 420 425 430 Phe Arg Val Ala Lys Ala Leu Glu Ala Gly Ile Val Trp Val Asn Asp 435 440 445 Val Cys Val His Ala Ala Glu Pro Gln Leu Pro Phe Gly Gly Val Lys 450 455 460 Gln Ser Ser Gly Ile Gly Arg Glu His Gly Gly Lys Tyr Gly Leu Glu 465 470 475 480 Glu Tyr Thr Glu Ile Lys Thr Val Thr Ile Arg Leu 485 490 29 3513 DNA Homo sapiens CDS (82)...(3150) 29 cgcacccagt caccagcgtt cgggagcctg tcgcagcggg accgacggaa tccggagcag 60 gcgacagggc gcagaagcgg g atg tac ttc tgt tgg ggc gcc gac tcc agg 111 Met Tyr Phe Cys Trp Gly Ala Asp Ser Arg 1 5 10 gag ctg cag cgc cgg agg acg gcg ggc agc ccc ggg gct gag cta ctg 159 Glu Leu Gln Arg Arg Arg Thr Ala Gly Ser Pro Gly Ala Glu Leu Leu 15 20 25 cag gcg gcc agc ggg gag cgc cac tct ctg ctg ctg ctg acc aac cac 207 Gln Ala Ala Ser Gly Glu Arg His Ser Leu Leu Leu Leu Thr Asn His 30 35 40 agg gtc ctc tcg tgc gga gac aac agc agg ggt cag ctg ggc cgc agg 255 Arg Val Leu Ser Cys Gly Asp Asn Ser Arg Gly Gln Leu Gly Arg Arg 45 50 55 ggc gcg cag cgc ggg gag ctg cca gaa cca att cag gca ttg gaa acc 303 Gly Ala Gln Arg Gly Glu Leu Pro Glu Pro Ile Gln Ala Leu Glu Thr 60 65 70 cta att gtt gat ctc gtg agc tgc ggg aag gag cac tcc ctg gct gtg 351 Leu Ile Val Asp Leu Val Ser Cys Gly Lys Glu His Ser Leu Ala Val 75 80 85 90 tgc cac aaa gga agg gtc ttc gca tgg gga gct ggt tct gaa ggg cag 399 Cys His Lys Gly Arg Val Phe Ala Trp Gly Ala Gly Ser Glu Gly Gln 95 100 105 ctg ggg att gga gaa ttc aag gaa ata agt ttc aca cct aag aaa ata 447 Leu Gly Ile Gly Glu Phe Lys Glu Ile Ser Phe Thr Pro Lys Lys Ile 110 115 120 atg act ctg aat gat ata aaa ata ata caa gtt tcc tgt gga cac tac 495 Met Thr Leu Asn Asp Ile Lys Ile Ile Gln Val Ser Cys Gly His Tyr 125 130 135 cac tcc ctg gca tta tca aaa gat agc caa gtg ttt tcg tgg gga aag 543 His Ser Leu Ala Leu Ser Lys Asp Ser Gln Val Phe Ser Trp Gly Lys 140 145 150 aac agc cat ggg cag ctg ggc ttg ggg aag gag ttc ccc tcc caa gcc 591 Asn Ser His Gly Gln Leu Gly Leu Gly Lys Glu Phe Pro Ser Gln Ala 155 160 165 170 agc ccg cag agg gtg agg tcc ctg gag ggg atc cca ctg gct cag gtg 639 Ser Pro Gln Arg Val Arg Ser Leu Glu Gly Ile Pro Leu Ala Gln Val 175 180 185 gct gcc gga ggg gct cac agc ttt gcc ctg tct ctc tgt ggg act tcg 687 Ala Ala Gly Gly Ala His Ser Phe Ala Leu Ser Leu Cys Gly Thr Ser 190 195 200 ttt ggc tgg gga agt aac agt gcc ggg cag ctg gcc ctc agt ggg cgt 735 Phe Gly Trp Gly Ser Asn Ser Ala Gly Gln Leu Ala Leu Ser Gly Arg 205 210 215 aat gtc cca gtg caa agc aac aag cct ctc tca gtc ggt gca ctg aag 783 Asn Val Pro Val Gln Ser Asn Lys Pro Leu Ser Val Gly Ala Leu Lys 220 225 230 aat cta ggt gtg gtt tat atc agc tgt ggt gat gca cac act gcg gtg 831 Asn Leu Gly Val Val Tyr Ile Ser Cys Gly Asp Ala His Thr Ala Val 235 240 245 250 ctt acc cag gac ggg aaa gtg ttc aca ttt gga gac aat cgc tct gga 879 Leu Thr Gln Asp Gly Lys Val Phe Thr Phe Gly Asp Asn Arg Ser Gly 255 260 265 cag ctg gga tac agc ccc act cct gag aag aga ggt cca caa ctt gtg 927 Gln Leu Gly Tyr Ser Pro Thr Pro Glu Lys Arg Gly Pro Gln Leu Val 270 275 280 gaa aga att gat ggc cta gtt tcg cag ata gat tgt gga agt tat cac 975 Glu Arg Ile Asp Gly Leu Val Ser Gln Ile Asp Cys Gly Ser Tyr His 285 290 295 acc ctg gca tat gtg cac acc act ggt cag gtg gta tct ttt ggt cat 1023 Thr Leu Ala Tyr Val His Thr Thr Gly Gln Val Val Ser Phe Gly His 300 305 310 gga cca agt gac aca agc aag cca act cat ccg gag gcc ctg aca gag 1071 Gly Pro Ser Asp Thr Ser Lys Pro Thr His Pro Glu Ala Leu Thr Glu 315 320 325 330 aac ttt gac att agc tgc ctg att tct gct gaa gac ttc gtg gat gtt 1119 Asn Phe Asp Ile Ser Cys Leu Ile Ser Ala Glu Asp Phe Val Asp Val 335 340 345 caa gtc aaa cac att ttt gct gga aca tat gcc aac ttt gtg aca act 1167 Gln Val Lys His Ile Phe Ala Gly Thr Tyr Ala Asn Phe Val Thr Thr 350 355 360 cat cag gat act agt tcc aca cgt gct ccc ggg aaa acc ctg cca gaa 1215 His Gln Asp Thr Ser Ser Thr Arg Ala Pro Gly Lys Thr Leu Pro Glu 365 370 375 ata agc cga att agc cag tcc atg gca gaa aaa tgg ata gca gtg aaa 1263 Ile Ser Arg Ile Ser Gln Ser Met Ala Glu Lys Trp Ile Ala Val Lys 380 385 390 aga aga agt act gaa cat gaa atg gct aaa agt gaa att aga atg ata 1311 Arg Arg Ser Thr Glu His Glu Met Ala Lys Ser Glu Ile Arg Met Ile 395 400 405 410 ttt tca tct cct gct tgt ctg act gca agt ttt tta aag aaa aga gga 1359 Phe Ser Ser Pro Ala Cys Leu Thr Ala Ser Phe Leu Lys Lys Arg Gly 415 420 425 act gga gaa acg act tcc att gat gtg gac tta gaa atg gca aga gat 1407 Thr Gly Glu Thr Thr Ser Ile Asp Val Asp Leu Glu Met Ala Arg Asp 430 435 440 acc ttc aag aag tta aca aaa aag gaa tgg att tct tcc atg ata act 1455 Thr Phe Lys Lys Leu Thr Lys Lys Glu Trp Ile Ser Ser Met Ile Thr 445 450 455 acg tgt ctc gag gat gat ctg ctc aga gct ctt cca tgc cat tct cca 1503 Thr Cys Leu Glu Asp Asp Leu Leu Arg Ala Leu Pro Cys His Ser Pro 460 465 470 cac caa gaa gct tta tca gtt ttc ctc ctg ctc cca gaa tgt cct gtg 1551 His Gln Glu Ala Leu Ser Val Phe Leu Leu Leu Pro Glu Cys Pro Val 475 480 485 490 atg cat gat tct aag aac tgg aag aac ctg gtg gtt cca ttt gca aag 1599 Met His Asp Ser Lys Asn Trp Lys Asn Leu Val Val Pro Phe Ala Lys 495 500 505 gct gtg tgt gaa atg agt aaa caa tct ttg caa gtc cta aag aag tgt 1647 Ala Val Cys Glu Met Ser Lys Gln Ser Leu Gln Val Leu Lys Lys Cys 510 515 520 tgg gca ttt ttg caa gaa tct tct ctg aat ccg ctg atc cag atg ctt 1695 Trp Ala Phe Leu Gln Glu Ser Ser Leu Asn Pro Leu Ile Gln Met Leu 525 530 535 aaa gca gcc atc atc tct cag ctg ctt cat cag act aaa acc gaa cag 1743 Lys Ala Ala Ile Ile Ser Gln Leu Leu His Gln Thr Lys Thr Glu Gln 540 545 550 gat cac tgt aat gtt aaa gct ctt tta gga atg atg aaa gaa ctg cat 1791 Asp His Cys Asn Val Lys Ala Leu Leu Gly Met Met Lys Glu Leu His 555 560 565 570 aag gta aac aaa gct aac tgt cga cta cca gaa aat act ttc aac ata 1839 Lys Val Asn Lys Ala Asn Cys Arg Leu Pro Glu Asn Thr Phe Asn Ile 575 580 585 aat gaa ctc tcc aac tta tta aac ttt tat ata gat aga gga aga cag 1887 Asn Glu Leu Ser Asn Leu Leu Asn Phe Tyr Ile Asp Arg Gly Arg Gln 590 595 600 ctc ttt cgg gat aac cac ctg ata cct gca gaa acc ccc agt cct gtt 1935 Leu Phe Arg Asp Asn His Leu Ile Pro Ala Glu Thr Pro Ser Pro Val 605 610 615 att ttc agt gat ttt cca ttt atc ttt aat tcg cta tcc aaa att aaa 1983 Ile Phe Ser Asp Phe Pro Phe Ile Phe Asn Ser Leu Ser Lys Ile Lys 620 625 630 tta ttg caa gct gat tca cat ata aag atg cag atg tca gaa aag aaa 2031 Leu Leu Gln Ala Asp Ser His Ile Lys Met Gln Met Ser Glu Lys Lys 635 640 645 650 gca tac atg ctt atg cat gaa aca att ctg caa aaa aag gat gaa ttt 2079 Ala Tyr Met Leu Met His Glu Thr Ile Leu Gln Lys Lys Asp Glu Phe 655 660 665 cct cca tca ccc aga ttt ata ctt aga gtc aga cga agt cgc ctg gtt 2127 Pro Pro Ser Pro Arg Phe Ile Leu Arg Val Arg Arg Ser Arg Leu Val 670 675 680 aaa gat gct ctg cgt caa tta agt caa gct gaa gct act gac ttc tgc 2175 Lys Asp Ala Leu Arg Gln Leu Ser Gln Ala Glu Ala Thr Asp Phe Cys 685 690 695 aaa gta tta gtg gtt gaa ttt att aat gaa att tgt cct gag tct gga 2223 Lys Val Leu Val Val Glu Phe Ile Asn Glu Ile Cys Pro Glu Ser Gly 700 705 710 ggg gtt agt tca gag ttc ttc cac tgt atg ttt gaa gag atg acc aag 2271 Gly Val Ser Ser Glu Phe Phe His Cys Met Phe Glu Glu Met Thr Lys 715 720 725 730 cca gaa tat gga atg ttc atg tat cct gaa atg ggt tcc tgc atg tgg 2319 Pro Glu Tyr Gly Met Phe Met Tyr Pro Glu Met Gly Ser Cys Met Trp 735 740 745 ttt cct gcc aag cct aaa cct gag aag aaa aga tat ttc ctc ttt gga 2367 Phe Pro Ala Lys Pro Lys Pro Glu Lys Lys Arg Tyr Phe Leu Phe Gly 750 755 760 atg ctg tgt gga ctc tcc tta ttc aat tta aat gtt gct aac ctt cct 2415 Met Leu Cys Gly Leu Ser Leu Phe Asn Leu Asn Val Ala Asn Leu Pro 765 770 775 ttc cca ctg gct ctg tat aaa aaa ctt ctg gac caa aag cca tca ttg 2463 Phe Pro Leu Ala Leu Tyr Lys Lys Leu Leu Asp Gln Lys Pro Ser Leu 780 785 790 gaa gat tta aaa gaa ctc agt cct cgg ttg ggg aag agt ttg caa gaa 2511 Glu Asp Leu Lys Glu Leu Ser Pro Arg Leu Gly Lys Ser Leu Gln Glu 795 800 805 810 gtt cta gat gat gct gct gat gac att gga gat gcg ctc tgc ata cgc 2559 Val Leu Asp Asp Ala Ala Asp Asp Ile Gly Asp Ala Leu Cys Ile Arg 815 820 825 ttt tct ata cac tgg gac caa aat gat gtt gac tta att cca aat ggg 2607 Phe

Ser Ile His Trp Asp Gln Asn Asp Val Asp Leu Ile Pro Asn Gly 830 835 840 atc tcc ata cct gtg gac caa acc aac aag aga gac tat gtt tct aag 2655 Ile Ser Ile Pro Val Asp Gln Thr Asn Lys Arg Asp Tyr Val Ser Lys 845 850 855 tat att gat tac att ttc aac gtc tct gta aaa gca gtt tat gag gaa 2703 Tyr Ile Asp Tyr Ile Phe Asn Val Ser Val Lys Ala Val Tyr Glu Glu 860 865 870 ttt cag aga gga ttt tat aga gtc tgt gag aag gag ata ctt aga cat 2751 Phe Gln Arg Gly Phe Tyr Arg Val Cys Glu Lys Glu Ile Leu Arg His 875 880 885 890 ttc tac cct gaa gaa cta atg aca gca atc att gga aat act gat tat 2799 Phe Tyr Pro Glu Glu Leu Met Thr Ala Ile Ile Gly Asn Thr Asp Tyr 895 900 905 gac tgg aaa cag ttt gaa cag aat tca aag tat gag caa gga tac caa 2847 Asp Trp Lys Gln Phe Glu Gln Asn Ser Lys Tyr Glu Gln Gly Tyr Gln 910 915 920 aaa tca cat cct act ata cag ttg ttt tgg aag gct ttc cac aaa cta 2895 Lys Ser His Pro Thr Ile Gln Leu Phe Trp Lys Ala Phe His Lys Leu 925 930 935 acc ttg gat gaa aag aaa aaa ttc ctc ttt ttc ctt aca gga cgt gat 2943 Thr Leu Asp Glu Lys Lys Lys Phe Leu Phe Phe Leu Thr Gly Arg Asp 940 945 950 agg ctg cat gca aga ggc ata cag aaa atg gaa ata gta ttt cgc tgt 2991 Arg Leu His Ala Arg Gly Ile Gln Lys Met Glu Ile Val Phe Arg Cys 955 960 965 970 cct gaa act ttc agt gaa aga gat cac cca aca tca ata act tgt cat 3039 Pro Glu Thr Phe Ser Glu Arg Asp His Pro Thr Ser Ile Thr Cys His 975 980 985 aat att ctc tcc ctc cct aag tat tct aca atg gaa aga atg gag gaa 3087 Asn Ile Leu Ser Leu Pro Lys Tyr Ser Thr Met Glu Arg Met Glu Glu 990 995 1000 gca ctt caa gta gcc atc aac aac aac aga gga ttt gtc tca ccc atg 3135 Ala Leu Gln Val Ala Ile Asn Asn Asn Arg Gly Phe Val Ser Pro Met 1005 1010 1015 ctc aca cag tca taa tcacctctga gagactcagg gtgggctttc tcacacttgg 3190 Leu Thr Gln Ser * 1020 atccttctgt tcttccttac acctaaataa tacaagagat taatgaatag tggttagaag 3250 tagttgaggg agagattggg ggaatgggga gatgatgatg atggtcaaag ggtgcaaaat 3310 ctcacacaag actgaggcag gagaataggg tacagagata gggatctaag gatgacttgg 3370 acacactccc tggcactgaa gagtctgaac actggcctgt gattggtcca ttccaggacc 3430 ttcatttgca taaggtatca aaccacatca gcctctgatt ggccatgggc cagacctgca 3490 ctctggccaa tgattggttc att 3513 30 1022 PRT Homo sapiens 30 Met Tyr Phe Cys Trp Gly Ala Asp Ser Arg Glu Leu Gln Arg Arg Arg 1 5 10 15 Thr Ala Gly Ser Pro Gly Ala Glu Leu Leu Gln Ala Ala Ser Gly Glu 20 25 30 Arg His Ser Leu Leu Leu Leu Thr Asn His Arg Val Leu Ser Cys Gly 35 40 45 Asp Asn Ser Arg Gly Gln Leu Gly Arg Arg Gly Ala Gln Arg Gly Glu 50 55 60 Leu Pro Glu Pro Ile Gln Ala Leu Glu Thr Leu Ile Val Asp Leu Val 65 70 75 80 Ser Cys Gly Lys Glu His Ser Leu Ala Val Cys His Lys Gly Arg Val 85 90 95 Phe Ala Trp Gly Ala Gly Ser Glu Gly Gln Leu Gly Ile Gly Glu Phe 100 105 110 Lys Glu Ile Ser Phe Thr Pro Lys Lys Ile Met Thr Leu Asn Asp Ile 115 120 125 Lys Ile Ile Gln Val Ser Cys Gly His Tyr His Ser Leu Ala Leu Ser 130 135 140 Lys Asp Ser Gln Val Phe Ser Trp Gly Lys Asn Ser His Gly Gln Leu 145 150 155 160 Gly Leu Gly Lys Glu Phe Pro Ser Gln Ala Ser Pro Gln Arg Val Arg 165 170 175 Ser Leu Glu Gly Ile Pro Leu Ala Gln Val Ala Ala Gly Gly Ala His 180 185 190 Ser Phe Ala Leu Ser Leu Cys Gly Thr Ser Phe Gly Trp Gly Ser Asn 195 200 205 Ser Ala Gly Gln Leu Ala Leu Ser Gly Arg Asn Val Pro Val Gln Ser 210 215 220 Asn Lys Pro Leu Ser Val Gly Ala Leu Lys Asn Leu Gly Val Val Tyr 225 230 235 240 Ile Ser Cys Gly Asp Ala His Thr Ala Val Leu Thr Gln Asp Gly Lys 245 250 255 Val Phe Thr Phe Gly Asp Asn Arg Ser Gly Gln Leu Gly Tyr Ser Pro 260 265 270 Thr Pro Glu Lys Arg Gly Pro Gln Leu Val Glu Arg Ile Asp Gly Leu 275 280 285 Val Ser Gln Ile Asp Cys Gly Ser Tyr His Thr Leu Ala Tyr Val His 290 295 300 Thr Thr Gly Gln Val Val Ser Phe Gly His Gly Pro Ser Asp Thr Ser 305 310 315 320 Lys Pro Thr His Pro Glu Ala Leu Thr Glu Asn Phe Asp Ile Ser Cys 325 330 335 Leu Ile Ser Ala Glu Asp Phe Val Asp Val Gln Val Lys His Ile Phe 340 345 350 Ala Gly Thr Tyr Ala Asn Phe Val Thr Thr His Gln Asp Thr Ser Ser 355 360 365 Thr Arg Ala Pro Gly Lys Thr Leu Pro Glu Ile Ser Arg Ile Ser Gln 370 375 380 Ser Met Ala Glu Lys Trp Ile Ala Val Lys Arg Arg Ser Thr Glu His 385 390 395 400 Glu Met Ala Lys Ser Glu Ile Arg Met Ile Phe Ser Ser Pro Ala Cys 405 410 415 Leu Thr Ala Ser Phe Leu Lys Lys Arg Gly Thr Gly Glu Thr Thr Ser 420 425 430 Ile Asp Val Asp Leu Glu Met Ala Arg Asp Thr Phe Lys Lys Leu Thr 435 440 445 Lys Lys Glu Trp Ile Ser Ser Met Ile Thr Thr Cys Leu Glu Asp Asp 450 455 460 Leu Leu Arg Ala Leu Pro Cys His Ser Pro His Gln Glu Ala Leu Ser 465 470 475 480 Val Phe Leu Leu Leu Pro Glu Cys Pro Val Met His Asp Ser Lys Asn 485 490 495 Trp Lys Asn Leu Val Val Pro Phe Ala Lys Ala Val Cys Glu Met Ser 500 505 510 Lys Gln Ser Leu Gln Val Leu Lys Lys Cys Trp Ala Phe Leu Gln Glu 515 520 525 Ser Ser Leu Asn Pro Leu Ile Gln Met Leu Lys Ala Ala Ile Ile Ser 530 535 540 Gln Leu Leu His Gln Thr Lys Thr Glu Gln Asp His Cys Asn Val Lys 545 550 555 560 Ala Leu Leu Gly Met Met Lys Glu Leu His Lys Val Asn Lys Ala Asn 565 570 575 Cys Arg Leu Pro Glu Asn Thr Phe Asn Ile Asn Glu Leu Ser Asn Leu 580 585 590 Leu Asn Phe Tyr Ile Asp Arg Gly Arg Gln Leu Phe Arg Asp Asn His 595 600 605 Leu Ile Pro Ala Glu Thr Pro Ser Pro Val Ile Phe Ser Asp Phe Pro 610 615 620 Phe Ile Phe Asn Ser Leu Ser Lys Ile Lys Leu Leu Gln Ala Asp Ser 625 630 635 640 His Ile Lys Met Gln Met Ser Glu Lys Lys Ala Tyr Met Leu Met His 645 650 655 Glu Thr Ile Leu Gln Lys Lys Asp Glu Phe Pro Pro Ser Pro Arg Phe 660 665 670 Ile Leu Arg Val Arg Arg Ser Arg Leu Val Lys Asp Ala Leu Arg Gln 675 680 685 Leu Ser Gln Ala Glu Ala Thr Asp Phe Cys Lys Val Leu Val Val Glu 690 695 700 Phe Ile Asn Glu Ile Cys Pro Glu Ser Gly Gly Val Ser Ser Glu Phe 705 710 715 720 Phe His Cys Met Phe Glu Glu Met Thr Lys Pro Glu Tyr Gly Met Phe 725 730 735 Met Tyr Pro Glu Met Gly Ser Cys Met Trp Phe Pro Ala Lys Pro Lys 740 745 750 Pro Glu Lys Lys Arg Tyr Phe Leu Phe Gly Met Leu Cys Gly Leu Ser 755 760 765 Leu Phe Asn Leu Asn Val Ala Asn Leu Pro Phe Pro Leu Ala Leu Tyr 770 775 780 Lys Lys Leu Leu Asp Gln Lys Pro Ser Leu Glu Asp Leu Lys Glu Leu 785 790 795 800 Ser Pro Arg Leu Gly Lys Ser Leu Gln Glu Val Leu Asp Asp Ala Ala 805 810 815 Asp Asp Ile Gly Asp Ala Leu Cys Ile Arg Phe Ser Ile His Trp Asp 820 825 830 Gln Asn Asp Val Asp Leu Ile Pro Asn Gly Ile Ser Ile Pro Val Asp 835 840 845 Gln Thr Asn Lys Arg Asp Tyr Val Ser Lys Tyr Ile Asp Tyr Ile Phe 850 855 860 Asn Val Ser Val Lys Ala Val Tyr Glu Glu Phe Gln Arg Gly Phe Tyr 865 870 875 880 Arg Val Cys Glu Lys Glu Ile Leu Arg His Phe Tyr Pro Glu Glu Leu 885 890 895 Met Thr Ala Ile Ile Gly Asn Thr Asp Tyr Asp Trp Lys Gln Phe Glu 900 905 910 Gln Asn Ser Lys Tyr Glu Gln Gly Tyr Gln Lys Ser His Pro Thr Ile 915 920 925 Gln Leu Phe Trp Lys Ala Phe His Lys Leu Thr Leu Asp Glu Lys Lys 930 935 940 Lys Phe Leu Phe Phe Leu Thr Gly Arg Asp Arg Leu His Ala Arg Gly 945 950 955 960 Ile Gln Lys Met Glu Ile Val Phe Arg Cys Pro Glu Thr Phe Ser Glu 965 970 975 Arg Asp His Pro Thr Ser Ile Thr Cys His Asn Ile Leu Ser Leu Pro 980 985 990 Lys Tyr Ser Thr Met Glu Arg Met Glu Glu Ala Leu Gln Val Ala Ile 995 1000 1005 Asn Asn Asn Arg Gly Phe Val Ser Pro Met Leu Thr Gln Ser 1010 1015 1020 31 3069 DNA Homo sapiens CDS (1)...(3069) 31 atg tac ttc tgt tgg ggc gcc gac tcc agg gag ctg cag cgc cgg agg 48 Met Tyr Phe Cys Trp Gly Ala Asp Ser Arg Glu Leu Gln Arg Arg Arg 1 5 10 15 acg gcg ggc agc ccc ggg gct gag cta ctg cag gcg gcc agc ggg gag 96 Thr Ala Gly Ser Pro Gly Ala Glu Leu Leu Gln Ala Ala Ser Gly Glu 20 25 30 cgc cac tct ctg ctg ctg ctg acc aac cac agg gtc ctc tcg tgc gga 144 Arg His Ser Leu Leu Leu Leu Thr Asn His Arg Val Leu Ser Cys Gly 35 40 45 gac aac agc agg ggt cag ctg ggc cgc agg ggc gcg cag cgc ggg gag 192 Asp Asn Ser Arg Gly Gln Leu Gly Arg Arg Gly Ala Gln Arg Gly Glu 50 55 60 ctg cca gaa cca att cag gca ttg gaa acc cta att gtt gat ctc gtg 240 Leu Pro Glu Pro Ile Gln Ala Leu Glu Thr Leu Ile Val Asp Leu Val 65 70 75 80 agc tgc ggg aag gag cac tcc ctg gct gtg tgc cac aaa gga agg gtc 288 Ser Cys Gly Lys Glu His Ser Leu Ala Val Cys His Lys Gly Arg Val 85 90 95 ttc gca tgg gga gct ggt tct gaa ggg cag ctg ggg att gga gaa ttc 336 Phe Ala Trp Gly Ala Gly Ser Glu Gly Gln Leu Gly Ile Gly Glu Phe 100 105 110 aag gaa ata agt ttc aca cct aag aaa ata atg act ctg aat gat ata 384 Lys Glu Ile Ser Phe Thr Pro Lys Lys Ile Met Thr Leu Asn Asp Ile 115 120 125 aaa ata ata caa gtt tcc tgt gga cac tac cac tcc ctg gca tta tca 432 Lys Ile Ile Gln Val Ser Cys Gly His Tyr His Ser Leu Ala Leu Ser 130 135 140 aaa gat agc caa gtg ttt tcg tgg gga aag aac agc cat ggg cag ctg 480 Lys Asp Ser Gln Val Phe Ser Trp Gly Lys Asn Ser His Gly Gln Leu 145 150 155 160 ggc ttg ggg aag gag ttc ccc tcc caa gcc agc ccg cag agg gtg agg 528 Gly Leu Gly Lys Glu Phe Pro Ser Gln Ala Ser Pro Gln Arg Val Arg 165 170 175 tcc ctg gag ggg atc cca ctg gct cag gtg gct gcc gga ggg gct cac 576 Ser Leu Glu Gly Ile Pro Leu Ala Gln Val Ala Ala Gly Gly Ala His 180 185 190 agc ttt gcc ctg tct ctc tgt ggg act tcg ttt ggc tgg gga agt aac 624 Ser Phe Ala Leu Ser Leu Cys Gly Thr Ser Phe Gly Trp Gly Ser Asn 195 200 205 agt gcc ggg cag ctg gcc ctc agt ggg cgt aat gtc cca gtg caa agc 672 Ser Ala Gly Gln Leu Ala Leu Ser Gly Arg Asn Val Pro Val Gln Ser 210 215 220 aac aag cct ctc tca gtc ggt gca ctg aag aat cta ggt gtg gtt tat 720 Asn Lys Pro Leu Ser Val Gly Ala Leu Lys Asn Leu Gly Val Val Tyr 225 230 235 240 atc agc tgt ggt gat gca cac act gcg gtg ctt acc cag gac ggg aaa 768 Ile Ser Cys Gly Asp Ala His Thr Ala Val Leu Thr Gln Asp Gly Lys 245 250 255 gtg ttc aca ttt gga gac aat cgc tct gga cag ctg gga tac agc ccc 816 Val Phe Thr Phe Gly Asp Asn Arg Ser Gly Gln Leu Gly Tyr Ser Pro 260 265 270 act cct gag aag aga ggt cca caa ctt gtg gaa aga att gat ggc cta 864 Thr Pro Glu Lys Arg Gly Pro Gln Leu Val Glu Arg Ile Asp Gly Leu 275 280 285 gtt tcg cag ata gat tgt gga agt tat cac acc ctg gca tat gtg cac 912 Val Ser Gln Ile Asp Cys Gly Ser Tyr His Thr Leu Ala Tyr Val His 290 295 300 acc act ggt cag gtg gta tct ttt ggt cat gga cca agt gac aca agc 960 Thr Thr Gly Gln Val Val Ser Phe Gly His Gly Pro Ser Asp Thr Ser 305 310 315 320 aag cca act cat ccg gag gcc ctg aca gag aac ttt gac att agc tgc 1008 Lys Pro Thr His Pro Glu Ala Leu Thr Glu Asn Phe Asp Ile Ser Cys 325 330 335 ctg att tct gct gaa gac ttc gtg gat gtt caa gtc aaa cac att ttt 1056 Leu Ile Ser Ala Glu Asp Phe Val Asp Val Gln Val Lys His Ile Phe 340 345 350 gct gga aca tat gcc aac ttt gtg aca act cat cag gat act agt tcc 1104 Ala Gly Thr Tyr Ala Asn Phe Val Thr Thr His Gln Asp Thr Ser Ser 355 360 365 aca cgt gct ccc ggg aaa acc ctg cca gaa ata agc cga att agc cag 1152 Thr Arg Ala Pro Gly Lys Thr Leu Pro Glu Ile Ser Arg Ile Ser Gln 370 375 380 tcc atg gca gaa aaa tgg ata gca gtg aaa aga aga agt act gaa cat 1200 Ser Met Ala Glu Lys Trp Ile Ala Val Lys Arg Arg Ser Thr Glu His 385 390 395 400 gaa atg gct aaa agt gaa att aga atg ata ttt tca tct cct gct tgt 1248 Glu Met Ala Lys Ser Glu Ile Arg Met Ile Phe Ser Ser Pro Ala Cys 405 410 415 ctg act gca agt ttt tta aag aaa aga gga act gga gaa acg act tcc 1296 Leu Thr Ala Ser Phe Leu Lys Lys Arg Gly Thr Gly Glu Thr Thr Ser 420 425 430 att gat gtg gac tta gaa atg gca aga gat acc ttc aag aag tta aca 1344 Ile Asp Val Asp Leu Glu Met Ala Arg Asp Thr Phe Lys Lys Leu Thr 435 440 445 aaa aag gaa tgg att tct tcc atg ata act acg tgt ctc gag gat gat 1392 Lys Lys Glu Trp Ile Ser Ser Met Ile Thr Thr Cys Leu Glu Asp Asp 450 455 460 ctg ctc aga gct ctt cca tgc cat tct cca cac caa gaa gct tta tca 1440 Leu Leu Arg Ala Leu Pro Cys His Ser Pro His Gln Glu Ala Leu Ser 465 470 475 480 gtt ttc ctc ctg ctc cca gaa tgt cct gtg atg cat gat tct aag aac 1488 Val Phe Leu Leu Leu Pro Glu Cys Pro Val Met His Asp Ser Lys Asn 485 490 495 tgg aag aac ctg gtg gtt cca ttt gca aag gct gtg tgt gaa atg agt 1536 Trp Lys Asn Leu Val Val Pro Phe Ala Lys Ala Val Cys Glu Met Ser 500 505 510 aaa caa tct ttg caa gtc cta aag aag tgt tgg gca ttt ttg caa gaa 1584 Lys Gln Ser Leu Gln Val Leu Lys Lys Cys Trp Ala Phe Leu Gln Glu 515 520 525 tct tct ctg aat ccg ctg atc cag atg ctt aaa gca gcc atc atc tct 1632 Ser Ser Leu Asn Pro Leu Ile Gln Met Leu Lys Ala Ala Ile Ile Ser 530 535 540 cag ctg ctt cat cag act aaa acc gaa cag gat cac tgt aat gtt aaa 1680 Gln Leu Leu His Gln Thr Lys Thr Glu Gln Asp His Cys Asn Val Lys 545 550 555 560 gct ctt tta gga atg atg aaa gaa ctg cat aag gta aac aaa gct aac 1728 Ala Leu Leu Gly Met Met Lys Glu Leu His Lys Val Asn Lys Ala Asn 565 570 575 tgt cga cta cca gaa aat act ttc aac ata aat gaa ctc tcc aac tta 1776 Cys Arg Leu Pro Glu Asn Thr Phe Asn Ile Asn Glu Leu Ser Asn Leu 580 585 590 tta aac ttt tat ata gat aga gga aga cag ctc ttt cgg gat aac cac 1824 Leu Asn Phe Tyr Ile Asp Arg Gly Arg Gln Leu Phe Arg Asp Asn His 595 600 605 ctg ata cct gca gaa acc ccc agt cct gtt att ttc agt gat ttt cca 1872 Leu Ile Pro Ala Glu Thr Pro Ser Pro Val Ile Phe Ser Asp Phe Pro 610 615 620 ttt atc ttt aat tcg cta tcc aaa att aaa tta ttg caa gct gat tca 1920 Phe Ile Phe Asn Ser Leu Ser Lys Ile Lys Leu Leu Gln Ala Asp Ser 625 630 635 640 cat ata aag atg cag atg tca gaa aag aaa gca tac atg ctt atg cat 1968 His Ile Lys Met Gln Met Ser Glu Lys Lys

Ala Tyr Met Leu Met His 645 650 655 gaa aca att ctg caa aaa aag gat gaa ttt cct cca tca ccc aga ttt 2016 Glu Thr Ile Leu Gln Lys Lys Asp Glu Phe Pro Pro Ser Pro Arg Phe 660 665 670 ata ctt aga gtc aga cga agt cgc ctg gtt aaa gat gct ctg cgt caa 2064 Ile Leu Arg Val Arg Arg Ser Arg Leu Val Lys Asp Ala Leu Arg Gln 675 680 685 tta agt caa gct gaa gct act gac ttc tgc aaa gta tta gtg gtt gaa 2112 Leu Ser Gln Ala Glu Ala Thr Asp Phe Cys Lys Val Leu Val Val Glu 690 695 700 ttt att aat gaa att tgt cct gag tct gga ggg gtt agt tca gag ttc 2160 Phe Ile Asn Glu Ile Cys Pro Glu Ser Gly Gly Val Ser Ser Glu Phe 705 710 715 720 ttc cac tgt atg ttt gaa gag atg acc aag cca gaa tat gga atg ttc 2208 Phe His Cys Met Phe Glu Glu Met Thr Lys Pro Glu Tyr Gly Met Phe 725 730 735 atg tat cct gaa atg ggt tcc tgc atg tgg ttt cct gcc aag cct aaa 2256 Met Tyr Pro Glu Met Gly Ser Cys Met Trp Phe Pro Ala Lys Pro Lys 740 745 750 cct gag aag aaa aga tat ttc ctc ttt gga atg ctg tgt gga ctc tcc 2304 Pro Glu Lys Lys Arg Tyr Phe Leu Phe Gly Met Leu Cys Gly Leu Ser 755 760 765 tta ttc aat tta aat gtt gct aac ctt cct ttc cca ctg gct ctg tat 2352 Leu Phe Asn Leu Asn Val Ala Asn Leu Pro Phe Pro Leu Ala Leu Tyr 770 775 780 aaa aaa ctt ctg gac caa aag cca tca ttg gaa gat tta aaa gaa ctc 2400 Lys Lys Leu Leu Asp Gln Lys Pro Ser Leu Glu Asp Leu Lys Glu Leu 785 790 795 800 agt cct cgg ttg ggg aag agt ttg caa gaa gtt cta gat gat gct gct 2448 Ser Pro Arg Leu Gly Lys Ser Leu Gln Glu Val Leu Asp Asp Ala Ala 805 810 815 gat gac att gga gat gcg ctc tgc ata cgc ttt tct ata cac tgg gac 2496 Asp Asp Ile Gly Asp Ala Leu Cys Ile Arg Phe Ser Ile His Trp Asp 820 825 830 caa aat gat gtt gac tta att cca aat ggg atc tcc ata cct gtg gac 2544 Gln Asn Asp Val Asp Leu Ile Pro Asn Gly Ile Ser Ile Pro Val Asp 835 840 845 caa acc aac aag aga gac tat gtt tct aag tat att gat tac att ttc 2592 Gln Thr Asn Lys Arg Asp Tyr Val Ser Lys Tyr Ile Asp Tyr Ile Phe 850 855 860 aac gtc tct gta aaa gca gtt tat gag gaa ttt cag aga gga ttt tat 2640 Asn Val Ser Val Lys Ala Val Tyr Glu Glu Phe Gln Arg Gly Phe Tyr 865 870 875 880 aga gtc tgt gag aag gag ata ctt aga cat ttc tac cct gaa gaa cta 2688 Arg Val Cys Glu Lys Glu Ile Leu Arg His Phe Tyr Pro Glu Glu Leu 885 890 895 atg aca gca atc att gga aat act gat tat gac tgg aaa cag ttt gaa 2736 Met Thr Ala Ile Ile Gly Asn Thr Asp Tyr Asp Trp Lys Gln Phe Glu 900 905 910 cag aat tca aag tat gag caa gga tac caa aaa tca cat cct act ata 2784 Gln Asn Ser Lys Tyr Glu Gln Gly Tyr Gln Lys Ser His Pro Thr Ile 915 920 925 cag ttg ttt tgg aag gct ttc cac aaa cta acc ttg gat gaa aag aaa 2832 Gln Leu Phe Trp Lys Ala Phe His Lys Leu Thr Leu Asp Glu Lys Lys 930 935 940 aaa ttc ctc ttt ttc ctt aca gga cgt gat agg ctg cat gca aga ggc 2880 Lys Phe Leu Phe Phe Leu Thr Gly Arg Asp Arg Leu His Ala Arg Gly 945 950 955 960 ata cag aaa atg gaa ata gta ttt cgc tgt cct gaa act ttc agt gaa 2928 Ile Gln Lys Met Glu Ile Val Phe Arg Cys Pro Glu Thr Phe Ser Glu 965 970 975 aga gat cac cca aca tca ata act tgt cat aat att ctc tcc ctc cct 2976 Arg Asp His Pro Thr Ser Ile Thr Cys His Asn Ile Leu Ser Leu Pro 980 985 990 aag tat tct aca atg gaa aga atg gag gaa gca ctt caa gta gcc atc 3024 Lys Tyr Ser Thr Met Glu Arg Met Glu Glu Ala Leu Gln Val Ala Ile 995 1000 1005 aac aac aac aga gga ttt gtc tca ccc atg ctc aca cag tca taa 3069 Asn Asn Asn Arg Gly Phe Val Ser Pro Met Leu Thr Gln Ser * 1010 1015 1020 32 70 PRT Artificial Sequence Consensus sequence 32 Asp Gly Arg Val Tyr Ser Leu Gly Cys Phe Arg Gly Glu Asn Gly Gln 1 5 10 15 Leu Gly Leu Gly Glu Glu Val Glu Glu Ser Lys Gly Gly Arg Gln Gly 20 25 30 Leu Glu Arg Leu Leu Val Pro Val Leu Val Met Leu Lys Ser Thr Ser 35 40 45 Ser Ser Leu Ser Glu Lys Val Val Ser Val Ala Ser Gly Gly Gln His 50 55 60 Thr Val Ala Leu Thr Lys 65 70 33 358 PRT Artificial Sequence Consensus sequence 33 Phe Leu Val Ser Lys Glu Met Phe Asn Pro Met Tyr Gly Leu Phe Phe 1 5 10 15 Tyr Ser Pro Glu Ser Asp Arg Tyr Thr Leu Tyr Ile Asp Pro Asn Ser 20 25 30 Asp Asp Lys Thr Thr Leu Leu Phe Pro Glu Pro Leu Asn Pro Phe Lys 35 40 45 Ala Asn Glu Glu His Leu Glu Tyr Phe Lys Phe Ile Gly Arg Val Val 50 55 60 Gly Leu Ala Leu Leu His Asn Arg Leu Leu Asp Leu Phe Phe Ala Arg 65 70 75 80 Ala Phe Tyr Lys Lys Leu Leu Arg Lys Ser Ile Lys Phe Val Thr Thr 85 90 95 Val Pro Ser Asp Val Glu Thr Ser Phe His Asp Leu Glu Ser Val Asp 100 105 110 Pro Glu Leu Tyr Asn Ser Leu Ile Lys Ile Leu Glu Asn Thr Glu Asp 115 120 125 Lys Glu Phe Glu Glu Val Ile Asn Leu Thr Asp Leu Thr Phe Ser Ile 130 135 140 Asp Leu Glu Glu Phe Gly Asn Asp Glu Lys Val Ser Lys Glu Tyr Val 145 150 155 160 Thr Val Glu Leu Ile Pro Asn Gly Arg Asn Ile Val Val Thr Lys Ser 165 170 175 Asn Lys Lys Glu Tyr Val His Leu Val Ile Gln Trp Arg Leu Val Lys 180 185 190 Arg Ile Glu Lys Gln Leu Lys Ala Phe Lys Glu Gly Phe Ser Glu Val 195 200 205 Ile Pro Glu Cys Asn Leu Ile Lys Ile Phe Asn Glu Glu Glu Leu Glu 210 215 220 Leu Leu Ile Gly Gly Val Glu Glu Glu Gly Asp Ile Asp Val Asp Asp 225 230 235 240 Leu Lys Ser Asn Thr Glu Tyr Glu Asp Glu Ser Ser Glu Gly Tyr Ser 245 250 255 Glu Asp Ser Gln Val Ile Gln Trp Phe Trp Glu Ile Val Glu Glu Phe 260 265 270 Asp Lys Glu Glu Arg Ala Lys Leu Leu Gln Phe Val Thr Gly Ser Pro 275 280 285 Arg Leu Pro Leu Gln Gly Phe Lys Ser Leu Glu Gly Ser Asn Gly Ile 290 295 300 Pro Lys Phe Thr Ile Glu Lys Ala Gly Thr Glu Asp Glu Arg Leu Pro 305 310 315 320 Thr Ala His Thr Cys Phe Asn Arg Leu Asp Leu Pro Lys Tyr Ser Ser 325 330 335 Lys Glu Ile Leu Arg Ser Lys Leu Leu Leu Ala Ile Glu Glu Cys Gly 340 345 350 Glu Gly Phe Gly Leu Val 355 34 11 PRT Artificial Sequence Conserved RCC1_2 pattern VARIANT (1)...(1) Xaa at position 1 can be L, I, V, M, F or A VARIANT (2)...(3) Xaa at positions 2 and 3 can be S, T, A, G or C VARIANT (5)...(6) Xaa = any amino acid VARIANT (8)...(8) Xaa at position 8 can be S, T, A, G, L or I VARIANT (9)...(9) Xaa at position 9 can be L, I, V, M, F or A VARIANT (10)...(10) Xaa = any amino acid VARIANT (11)...(11) Xaa at position 11 can be L, I, V or M 34 Xaa Xaa Xaa Gly Xaa Xaa His Xaa Xaa Xaa Xaa 1 5 10 35 3633 DNA Homo sapiens CDS (23)...(3415) 35 cgcaagcggg acactgtggt gg atg caa ttc ccc tcg cct cca gcc gcg agg 52 Met Gln Phe Pro Ser Pro Pro Ala Ala Arg 1 5 10 agc tcc ccg gcg ccg cag gca gcg tcc tcc tcc gaa gca gct gca cct 100 Ser Ser Pro Ala Pro Gln Ala Ala Ser Ser Ser Glu Ala Ala Ala Pro 15 20 25 gca act ggg cag cct gga ccc tcg tgc cct gtt ccc ggg acc tcg cgc 148 Ala Thr Gly Gln Pro Gly Pro Ser Cys Pro Val Pro Gly Thr Ser Arg 30 35 40 agg ggg cgc ccc ggg aca ccc cct gcg ggc cgg gtg gag gag gaa gag 196 Arg Gly Arg Pro Gly Thr Pro Pro Ala Gly Arg Val Glu Glu Glu Glu 45 50 55 gag gag gag gaa gaa gac gtg gac aag gac ccc cat cct acc cag aac 244 Glu Glu Glu Glu Glu Asp Val Asp Lys Asp Pro His Pro Thr Gln Asn 60 65 70 acc tgc ctg cgc tgc cgc cac ttc tct tta agg gag agg aaa aga gag 292 Thr Cys Leu Arg Cys Arg His Phe Ser Leu Arg Glu Arg Lys Arg Glu 75 80 85 90 cct agg aga acc atg ggg ggc tgc gaa gtc cgg gaa ttt ctt ttg caa 340 Pro Arg Arg Thr Met Gly Gly Cys Glu Val Arg Glu Phe Leu Leu Gln 95 100 105 ttt ggt ttc ttc ttg cct ctg ctg aca gcg tgg cca ggc gac tgc agt 388 Phe Gly Phe Phe Leu Pro Leu Leu Thr Ala Trp Pro Gly Asp Cys Ser 110 115 120 cac gtc tcc aac aac caa gtt gtg ttg ctt gat aca aca act gta ctg 436 His Val Ser Asn Asn Gln Val Val Leu Leu Asp Thr Thr Thr Val Leu 125 130 135 gga gag cta gga tgg aaa aca tat cca tta aat ggg tgg gat gcc atc 484 Gly Glu Leu Gly Trp Lys Thr Tyr Pro Leu Asn Gly Trp Asp Ala Ile 140 145 150 act gaa atg gat gaa cat aat agg ccc att cac aca tac cag gta tgt 532 Thr Glu Met Asp Glu His Asn Arg Pro Ile His Thr Tyr Gln Val Cys 155 160 165 170 aat gta atg gaa cca aac caa aac aac tgg ctt cgt aca aac tgg atc 580 Asn Val Met Glu Pro Asn Gln Asn Asn Trp Leu Arg Thr Asn Trp Ile 175 180 185 tcc cgt gat gca gct cag aaa att tat gtg gaa atg aaa ttc aca cta 628 Ser Arg Asp Ala Ala Gln Lys Ile Tyr Val Glu Met Lys Phe Thr Leu 190 195 200 agg gat tgt aac agc atc cca tgg gtc ttg ggg act tgc aaa gaa aca 676 Arg Asp Cys Asn Ser Ile Pro Trp Val Leu Gly Thr Cys Lys Glu Thr 205 210 215 ttt aat ctg ttt tat atg gaa tca gat gag tcc cac gga att aaa ttc 724 Phe Asn Leu Phe Tyr Met Glu Ser Asp Glu Ser His Gly Ile Lys Phe 220 225 230 aag cca aac cag tat aca aag atc gac aca att gct gct gat gag agt 772 Lys Pro Asn Gln Tyr Thr Lys Ile Asp Thr Ile Ala Ala Asp Glu Ser 235 240 245 250 ttt acc cag atg gat ttg ggt gat cgc atc ctc aaa ctc aac act gaa 820 Phe Thr Gln Met Asp Leu Gly Asp Arg Ile Leu Lys Leu Asn Thr Glu 255 260 265 att cgt gag gtg ggg cct ata gaa agg aaa gga ttt tat ctg gct ttt 868 Ile Arg Glu Val Gly Pro Ile Glu Arg Lys Gly Phe Tyr Leu Ala Phe 270 275 280 caa gac att ggg gcg tgc att gcc ctg gtt tca gtc cgt gtt ttc tac 916 Gln Asp Ile Gly Ala Cys Ile Ala Leu Val Ser Val Arg Val Phe Tyr 285 290 295 aag aaa tgc ccc ttc act gtt cgt aac ttg gcc atg ttt cct gat acc 964 Lys Lys Cys Pro Phe Thr Val Arg Asn Leu Ala Met Phe Pro Asp Thr 300 305 310 att cca agg gtt gat tcc tcc tct ttg gtt gaa gta cgg ggt tct tgt 1012 Ile Pro Arg Val Asp Ser Ser Ser Leu Val Glu Val Arg Gly Ser Cys 315 320 325 330 gtg aag agt gct gaa gag cgt gac act cct aaa ctg tat tgt gga gct 1060 Val Lys Ser Ala Glu Glu Arg Asp Thr Pro Lys Leu Tyr Cys Gly Ala 335 340 345 gat gga gat tgg ctg gtt cct ctt gga agg tgc atc tgc agt aca gga 1108 Asp Gly Asp Trp Leu Val Pro Leu Gly Arg Cys Ile Cys Ser Thr Gly 350 355 360 tat gaa gaa att gag ggt tct tgc cat gct tgc aga cca gga ttc tat 1156 Tyr Glu Glu Ile Glu Gly Ser Cys His Ala Cys Arg Pro Gly Phe Tyr 365 370 375 aaa gct ttt gct ggg aac aca aaa tgt tct aaa tgt cct cca cac agt 1204 Lys Ala Phe Ala Gly Asn Thr Lys Cys Ser Lys Cys Pro Pro His Ser 380 385 390 tta aca tac atg gaa gca act tct gtc tgt cag tgt gaa aag ggt tat 1252 Leu Thr Tyr Met Glu Ala Thr Ser Val Cys Gln Cys Glu Lys Gly Tyr 395 400 405 410 ttc cga gct gaa aaa gac cca cct tct atg gca tgt acc agg cca cct 1300 Phe Arg Ala Glu Lys Asp Pro Pro Ser Met Ala Cys Thr Arg Pro Pro 415 420 425 tca gct cct agg aat gtg gtt ttt aac atc aat gaa aca gcc ctt att 1348 Ser Ala Pro Arg Asn Val Val Phe Asn Ile Asn Glu Thr Ala Leu Ile 430 435 440 ttg gaa tgg agc cca cca agt gac aca gga ggg aga aaa gat ctc aca 1396 Leu Glu Trp Ser Pro Pro Ser Asp Thr Gly Gly Arg Lys Asp Leu Thr 445 450 455 tac agt gta atc tgt aag aaa tgt ggc tta gac acc agc cag tgt gag 1444 Tyr Ser Val Ile Cys Lys Lys Cys Gly Leu Asp Thr Ser Gln Cys Glu 460 465 470 gac tgt ggt gga gga ctc cgc ttc atc cca aga cat aca ggc ctg atc 1492 Asp Cys Gly Gly Gly Leu Arg Phe Ile Pro Arg His Thr Gly Leu Ile 475 480 485 490 aac aat tcc gtg ata gta ctt gac ttt gtg tct cac gtg aat tac acc 1540 Asn Asn Ser Val Ile Val Leu Asp Phe Val Ser His Val Asn Tyr Thr 495 500 505 ttt gaa ata gaa gca atg aat gga gtt tct gag ttg agt ttt tct ccc 1588 Phe Glu Ile Glu Ala Met Asn Gly Val Ser Glu Leu Ser Phe Ser Pro 510 515 520 aag cca ttc aca gct att aca gtg acc acg gat caa gat gca cct tcc 1636 Lys Pro Phe Thr Ala Ile Thr Val Thr Thr Asp Gln Asp Ala Pro Ser 525 530 535 ctg ata ggt gtg gta agg aag gac tgg gca tcc caa aat agc att gcc 1684 Leu Ile Gly Val Val Arg Lys Asp Trp Ala Ser Gln Asn Ser Ile Ala 540 545 550 cta tca tgg caa gca cct gct ttt tcc aat gga gcc att ctg gac tac 1732 Leu Ser Trp Gln Ala Pro Ala Phe Ser Asn Gly Ala Ile Leu Asp Tyr 555 560 565 570 gag atc aag tac tat gag aag gaa cat gag cag ctg acc tac tct tcc 1780 Glu Ile Lys Tyr Tyr Glu Lys Glu His Glu Gln Leu Thr Tyr Ser Ser 575 580 585 aca agg tcc aaa gcc ccc agt gtc atc atc aca ggt ctt aag cca gcc 1828 Thr Arg Ser Lys Ala Pro Ser Val Ile Ile Thr Gly Leu Lys Pro Ala 590 595 600 acc aaa tat gta ttt cac atc cga gtg aga act gcg aca gga tac agt 1876 Thr Lys Tyr Val Phe His Ile Arg Val Arg Thr Ala Thr Gly Tyr Ser 605 610 615 ggc tac agt cag aaa ttt gaa ttt gaa aca gga gat gaa act tct gac 1924 Gly Tyr Ser Gln Lys Phe Glu Phe Glu Thr Gly Asp Glu Thr Ser Asp 620 625 630 atg gca gca gaa caa gga cag att ctc gtg ata gcc acc gcc gct gtt 1972 Met Ala Ala Glu Gln Gly Gln Ile Leu Val Ile Ala Thr Ala Ala Val 635 640 645 650 ggc gga ttc act ctc ctc gtc atc ctc act tta ttc ttc ttg atc act 2020 Gly Gly Phe Thr Leu Leu Val Ile Leu Thr Leu Phe Phe Leu Ile Thr 655 660 665 ggg aga tgt cag tgg tac ata aaa gcc aag atg aag tca gaa gag aag 2068 Gly Arg Cys Gln Trp Tyr Ile Lys Ala Lys Met Lys Ser Glu Glu Lys 670 675 680 aga aga aac cac tta cag aat ggg cat ttg cgc ttc ccg gga att aaa 2116 Arg Arg Asn His Leu Gln Asn Gly His Leu Arg Phe Pro Gly Ile Lys 685 690 695 act tac att gat cca gat aca tat gaa gac cca tcc cta gca gtc cat 2164 Thr Tyr Ile Asp Pro Asp Thr Tyr Glu Asp Pro Ser Leu Ala Val His 700 705 710 gaa ttt gca aag gag att gat ccc tca aga att cgt att gag aga gtc 2212 Glu Phe Ala Lys Glu Ile Asp Pro Ser Arg Ile Arg Ile Glu Arg Val 715 720 725 730 att ggg gca ggt gaa ttt gga gaa gtc tgt agt ggg cgt ttg aag aca 2260 Ile Gly Ala Gly Glu Phe Gly Glu Val Cys Ser Gly Arg Leu Lys Thr 735 740 745 cca ggg aaa aga gag atc cca gtt gcc att aaa act ttg aaa ggt ggc 2308 Pro Gly Lys Arg Glu Ile Pro Val Ala Ile Lys Thr Leu Lys Gly Gly 750 755 760 cac atg gat cgg caa aga aga gat ttt cta aga gaa gct agt atc atg 2356 His Met Asp Arg Gln Arg Arg Asp Phe Leu Arg Glu Ala Ser Ile Met 765 770 775 ggc cag ttt gac cat cca aac atc att cgc cta gaa ggg gtt gtc acc 2404 Gly Gln Phe Asp His Pro Asn Ile Ile Arg Leu Glu Gly Val Val Thr 780 785 790 aaa aga tcc ttc ccg gcc att ggg gtg gag gcg ttt tgc ccc agc ttc 2452 Lys Arg Ser Phe Pro Ala Ile Gly Val Glu Ala Phe Cys Pro Ser Phe 795 800 805 810 ctg agg gca ggg ttt tta aat agc atc cag gcc ccg cat cca gtg cca 2500 Leu Arg Ala Gly Phe Leu Asn

Ser Ile Gln Ala Pro His Pro Val Pro 815 820 825 ggg gga gga tct ttg ccc ccc agg att cct gct ggc aga cca gta atg 2548 Gly Gly Gly Ser Leu Pro Pro Arg Ile Pro Ala Gly Arg Pro Val Met 830 835 840 att gtg gtg gaa tat atg gag aat gga tcc cta gac tcc ttt ttg cgg 2596 Ile Val Val Glu Tyr Met Glu Asn Gly Ser Leu Asp Ser Phe Leu Arg 845 850 855 aag cat gat ggc cac ttc aca gtc atc cag ttg gtc gga atg ctc cga 2644 Lys His Asp Gly His Phe Thr Val Ile Gln Leu Val Gly Met Leu Arg 860 865 870 ggc att gca tca ggc atg aag tat ctt tct gat atg ggt tat gtt cat 2692 Gly Ile Ala Ser Gly Met Lys Tyr Leu Ser Asp Met Gly Tyr Val His 875 880 885 890 cga gac cta gcg gct cgg aat ata ctg gtc aat agc aac tta gta tgc 2740 Arg Asp Leu Ala Ala Arg Asn Ile Leu Val Asn Ser Asn Leu Val Cys 895 900 905 aaa gtt tct gat ttt ggt ctc tcc aga gtg ctg gaa gat gat cca gaa 2788 Lys Val Ser Asp Phe Gly Leu Ser Arg Val Leu Glu Asp Asp Pro Glu 910 915 920 gct gct tat aca aca act ggt gga aaa atc ccc ata agg tgg aca gcc 2836 Ala Ala Tyr Thr Thr Thr Gly Gly Lys Ile Pro Ile Arg Trp Thr Ala 925 930 935 cca gaa gcc atc gcc tac aga aaa ttc tcc tca gca agc gat gca tgg 2884 Pro Glu Ala Ile Ala Tyr Arg Lys Phe Ser Ser Ala Ser Asp Ala Trp 940 945 950 agc tat ggc att gtc atg tgg gag gtc atg tcc tat gga gag aga cct 2932 Ser Tyr Gly Ile Val Met Trp Glu Val Met Ser Tyr Gly Glu Arg Pro 955 960 965 970 tat tgg gaa atg tct aac caa gat gtc att ctg tcc att gaa gaa ggg 2980 Tyr Trp Glu Met Ser Asn Gln Asp Val Ile Leu Ser Ile Glu Glu Gly 975 980 985 tac aga ctt cca gct ccc atg ggc tgt cca gca tct cta cac cag ctg 3028 Tyr Arg Leu Pro Ala Pro Met Gly Cys Pro Ala Ser Leu His Gln Leu 990 995 1000 atg ctc cac tgc tgg cag aag gag aga aat cac aga cca aaa ttt act 3076 Met Leu His Cys Trp Gln Lys Glu Arg Asn His Arg Pro Lys Phe Thr 1005 1010 1015 gac att gtc agc ttc ctt gac aaa ctg atc cga aat ccc agt gcc ctt 3124 Asp Ile Val Ser Phe Leu Asp Lys Leu Ile Arg Asn Pro Ser Ala Leu 1020 1025 1030 cac acc ctg gtg gag gac atc ctt gta atg cca gag tcc cct ggt gaa 3172 His Thr Leu Val Glu Asp Ile Leu Val Met Pro Glu Ser Pro Gly Glu 1035 1040 1045 1050 gtt ccg gaa tat cct ttg ttt gtc aca gtt ggt gac tgg cta gat tct 3220 Val Pro Glu Tyr Pro Leu Phe Val Thr Val Gly Asp Trp Leu Asp Ser 1055 1060 1065 ata aag atg ggg caa tac aag aat aac ttc gtg gca gca ggg ttt aca 3268 Ile Lys Met Gly Gln Tyr Lys Asn Asn Phe Val Ala Ala Gly Phe Thr 1070 1075 1080 aca ttt gac ctg att tca aga atg agc att gat gac att aga aga att 3316 Thr Phe Asp Leu Ile Ser Arg Met Ser Ile Asp Asp Ile Arg Arg Ile 1085 1090 1095 gga gtc ata ctt att gga cac cag aga cga ata gtc agc agc ata cag 3364 Gly Val Ile Leu Ile Gly His Gln Arg Arg Ile Val Ser Ser Ile Gln 1100 1105 1110 act tta cgt tta cac atg atg cac ata cag gag aag gga ttt cat gta 3412 Thr Leu Arg Leu His Met Met His Ile Gln Glu Lys Gly Phe His Val 1115 1120 1125 1130 tga aagtaccaca agcacctgtg ttttgtgcct cagcatttct aaaatgaacg 3465 * atatcctctc tactactctc tcttctgatt ctccaaacat cacttcacaa actgcagtct 3525 tctgttcaga ctataggcac acaccttatg tttatgcttc caaccaggat tttaaaatca 3585 tgctacataa atccgttctg aataacctgc aactaaaaaa aaaaaaaa 3633 36 1130 PRT Homo sapiens 36 Met Gln Phe Pro Ser Pro Pro Ala Ala Arg Ser Ser Pro Ala Pro Gln 1 5 10 15 Ala Ala Ser Ser Ser Glu Ala Ala Ala Pro Ala Thr Gly Gln Pro Gly 20 25 30 Pro Ser Cys Pro Val Pro Gly Thr Ser Arg Arg Gly Arg Pro Gly Thr 35 40 45 Pro Pro Ala Gly Arg Val Glu Glu Glu Glu Glu Glu Glu Glu Glu Asp 50 55 60 Val Asp Lys Asp Pro His Pro Thr Gln Asn Thr Cys Leu Arg Cys Arg 65 70 75 80 His Phe Ser Leu Arg Glu Arg Lys Arg Glu Pro Arg Arg Thr Met Gly 85 90 95 Gly Cys Glu Val Arg Glu Phe Leu Leu Gln Phe Gly Phe Phe Leu Pro 100 105 110 Leu Leu Thr Ala Trp Pro Gly Asp Cys Ser His Val Ser Asn Asn Gln 115 120 125 Val Val Leu Leu Asp Thr Thr Thr Val Leu Gly Glu Leu Gly Trp Lys 130 135 140 Thr Tyr Pro Leu Asn Gly Trp Asp Ala Ile Thr Glu Met Asp Glu His 145 150 155 160 Asn Arg Pro Ile His Thr Tyr Gln Val Cys Asn Val Met Glu Pro Asn 165 170 175 Gln Asn Asn Trp Leu Arg Thr Asn Trp Ile Ser Arg Asp Ala Ala Gln 180 185 190 Lys Ile Tyr Val Glu Met Lys Phe Thr Leu Arg Asp Cys Asn Ser Ile 195 200 205 Pro Trp Val Leu Gly Thr Cys Lys Glu Thr Phe Asn Leu Phe Tyr Met 210 215 220 Glu Ser Asp Glu Ser His Gly Ile Lys Phe Lys Pro Asn Gln Tyr Thr 225 230 235 240 Lys Ile Asp Thr Ile Ala Ala Asp Glu Ser Phe Thr Gln Met Asp Leu 245 250 255 Gly Asp Arg Ile Leu Lys Leu Asn Thr Glu Ile Arg Glu Val Gly Pro 260 265 270 Ile Glu Arg Lys Gly Phe Tyr Leu Ala Phe Gln Asp Ile Gly Ala Cys 275 280 285 Ile Ala Leu Val Ser Val Arg Val Phe Tyr Lys Lys Cys Pro Phe Thr 290 295 300 Val Arg Asn Leu Ala Met Phe Pro Asp Thr Ile Pro Arg Val Asp Ser 305 310 315 320 Ser Ser Leu Val Glu Val Arg Gly Ser Cys Val Lys Ser Ala Glu Glu 325 330 335 Arg Asp Thr Pro Lys Leu Tyr Cys Gly Ala Asp Gly Asp Trp Leu Val 340 345 350 Pro Leu Gly Arg Cys Ile Cys Ser Thr Gly Tyr Glu Glu Ile Glu Gly 355 360 365 Ser Cys His Ala Cys Arg Pro Gly Phe Tyr Lys Ala Phe Ala Gly Asn 370 375 380 Thr Lys Cys Ser Lys Cys Pro Pro His Ser Leu Thr Tyr Met Glu Ala 385 390 395 400 Thr Ser Val Cys Gln Cys Glu Lys Gly Tyr Phe Arg Ala Glu Lys Asp 405 410 415 Pro Pro Ser Met Ala Cys Thr Arg Pro Pro Ser Ala Pro Arg Asn Val 420 425 430 Val Phe Asn Ile Asn Glu Thr Ala Leu Ile Leu Glu Trp Ser Pro Pro 435 440 445 Ser Asp Thr Gly Gly Arg Lys Asp Leu Thr Tyr Ser Val Ile Cys Lys 450 455 460 Lys Cys Gly Leu Asp Thr Ser Gln Cys Glu Asp Cys Gly Gly Gly Leu 465 470 475 480 Arg Phe Ile Pro Arg His Thr Gly Leu Ile Asn Asn Ser Val Ile Val 485 490 495 Leu Asp Phe Val Ser His Val Asn Tyr Thr Phe Glu Ile Glu Ala Met 500 505 510 Asn Gly Val Ser Glu Leu Ser Phe Ser Pro Lys Pro Phe Thr Ala Ile 515 520 525 Thr Val Thr Thr Asp Gln Asp Ala Pro Ser Leu Ile Gly Val Val Arg 530 535 540 Lys Asp Trp Ala Ser Gln Asn Ser Ile Ala Leu Ser Trp Gln Ala Pro 545 550 555 560 Ala Phe Ser Asn Gly Ala Ile Leu Asp Tyr Glu Ile Lys Tyr Tyr Glu 565 570 575 Lys Glu His Glu Gln Leu Thr Tyr Ser Ser Thr Arg Ser Lys Ala Pro 580 585 590 Ser Val Ile Ile Thr Gly Leu Lys Pro Ala Thr Lys Tyr Val Phe His 595 600 605 Ile Arg Val Arg Thr Ala Thr Gly Tyr Ser Gly Tyr Ser Gln Lys Phe 610 615 620 Glu Phe Glu Thr Gly Asp Glu Thr Ser Asp Met Ala Ala Glu Gln Gly 625 630 635 640 Gln Ile Leu Val Ile Ala Thr Ala Ala Val Gly Gly Phe Thr Leu Leu 645 650 655 Val Ile Leu Thr Leu Phe Phe Leu Ile Thr Gly Arg Cys Gln Trp Tyr 660 665 670 Ile Lys Ala Lys Met Lys Ser Glu Glu Lys Arg Arg Asn His Leu Gln 675 680 685 Asn Gly His Leu Arg Phe Pro Gly Ile Lys Thr Tyr Ile Asp Pro Asp 690 695 700 Thr Tyr Glu Asp Pro Ser Leu Ala Val His Glu Phe Ala Lys Glu Ile 705 710 715 720 Asp Pro Ser Arg Ile Arg Ile Glu Arg Val Ile Gly Ala Gly Glu Phe 725 730 735 Gly Glu Val Cys Ser Gly Arg Leu Lys Thr Pro Gly Lys Arg Glu Ile 740 745 750 Pro Val Ala Ile Lys Thr Leu Lys Gly Gly His Met Asp Arg Gln Arg 755 760 765 Arg Asp Phe Leu Arg Glu Ala Ser Ile Met Gly Gln Phe Asp His Pro 770 775 780 Asn Ile Ile Arg Leu Glu Gly Val Val Thr Lys Arg Ser Phe Pro Ala 785 790 795 800 Ile Gly Val Glu Ala Phe Cys Pro Ser Phe Leu Arg Ala Gly Phe Leu 805 810 815 Asn Ser Ile Gln Ala Pro His Pro Val Pro Gly Gly Gly Ser Leu Pro 820 825 830 Pro Arg Ile Pro Ala Gly Arg Pro Val Met Ile Val Val Glu Tyr Met 835 840 845 Glu Asn Gly Ser Leu Asp Ser Phe Leu Arg Lys His Asp Gly His Phe 850 855 860 Thr Val Ile Gln Leu Val Gly Met Leu Arg Gly Ile Ala Ser Gly Met 865 870 875 880 Lys Tyr Leu Ser Asp Met Gly Tyr Val His Arg Asp Leu Ala Ala Arg 885 890 895 Asn Ile Leu Val Asn Ser Asn Leu Val Cys Lys Val Ser Asp Phe Gly 900 905 910 Leu Ser Arg Val Leu Glu Asp Asp Pro Glu Ala Ala Tyr Thr Thr Thr 915 920 925 Gly Gly Lys Ile Pro Ile Arg Trp Thr Ala Pro Glu Ala Ile Ala Tyr 930 935 940 Arg Lys Phe Ser Ser Ala Ser Asp Ala Trp Ser Tyr Gly Ile Val Met 945 950 955 960 Trp Glu Val Met Ser Tyr Gly Glu Arg Pro Tyr Trp Glu Met Ser Asn 965 970 975 Gln Asp Val Ile Leu Ser Ile Glu Glu Gly Tyr Arg Leu Pro Ala Pro 980 985 990 Met Gly Cys Pro Ala Ser Leu His Gln Leu Met Leu His Cys Trp Gln 995 1000 1005 Lys Glu Arg Asn His Arg Pro Lys Phe Thr Asp Ile Val Ser Phe Leu 1010 1015 1020 Asp Lys Leu Ile Arg Asn Pro Ser Ala Leu His Thr Leu Val Glu Asp 1025 1030 1035 1040 Ile Leu Val Met Pro Glu Ser Pro Gly Glu Val Pro Glu Tyr Pro Leu 1045 1050 1055 Phe Val Thr Val Gly Asp Trp Leu Asp Ser Ile Lys Met Gly Gln Tyr 1060 1065 1070 Lys Asn Asn Phe Val Ala Ala Gly Phe Thr Thr Phe Asp Leu Ile Ser 1075 1080 1085 Arg Met Ser Ile Asp Asp Ile Arg Arg Ile Gly Val Ile Leu Ile Gly 1090 1095 1100 His Gln Arg Arg Ile Val Ser Ser Ile Gln Thr Leu Arg Leu His Met 1105 1110 1115 1120 Met His Ile Gln Glu Lys Gly Phe His Val 1125 1130 37 3393 DNA Homo sapiens CDS (1)...(3393) 37 atg caa ttc ccc tcg cct cca gcc gcg agg agc tcc ccg gcg ccg cag 48 Met Gln Phe Pro Ser Pro Pro Ala Ala Arg Ser Ser Pro Ala Pro Gln 1 5 10 15 gca gcg tcc tcc tcc gaa gca gct gca cct gca act ggg cag cct gga 96 Ala Ala Ser Ser Ser Glu Ala Ala Ala Pro Ala Thr Gly Gln Pro Gly 20 25 30 ccc tcg tgc cct gtt ccc ggg acc tcg cgc agg ggg cgc ccc ggg aca 144 Pro Ser Cys Pro Val Pro Gly Thr Ser Arg Arg Gly Arg Pro Gly Thr 35 40 45 ccc cct gcg ggc cgg gtg gag gag gaa gag gag gag gag gaa gaa gac 192 Pro Pro Ala Gly Arg Val Glu Glu Glu Glu Glu Glu Glu Glu Glu Asp 50 55 60 gtg gac aag gac ccc cat cct acc cag aac acc tgc ctg cgc tgc cgc 240 Val Asp Lys Asp Pro His Pro Thr Gln Asn Thr Cys Leu Arg Cys Arg 65 70 75 80 cac ttc tct tta agg gag agg aaa aga gag cct agg aga acc atg ggg 288 His Phe Ser Leu Arg Glu Arg Lys Arg Glu Pro Arg Arg Thr Met Gly 85 90 95 ggc tgc gaa gtc cgg gaa ttt ctt ttg caa ttt ggt ttc ttc ttg cct 336 Gly Cys Glu Val Arg Glu Phe Leu Leu Gln Phe Gly Phe Phe Leu Pro 100 105 110 ctg ctg aca gcg tgg cca ggc gac tgc agt cac gtc tcc aac aac caa 384 Leu Leu Thr Ala Trp Pro Gly Asp Cys Ser His Val Ser Asn Asn Gln 115 120 125 gtt gtg ttg ctt gat aca aca act gta ctg gga gag cta gga tgg aaa 432 Val Val Leu Leu Asp Thr Thr Thr Val Leu Gly Glu Leu Gly Trp Lys 130 135 140 aca tat cca tta aat ggg tgg gat gcc atc act gaa atg gat gaa cat 480 Thr Tyr Pro Leu Asn Gly Trp Asp Ala Ile Thr Glu Met Asp Glu His 145 150 155 160 aat agg ccc att cac aca tac cag gta tgt aat gta atg gaa cca aac 528 Asn Arg Pro Ile His Thr Tyr Gln Val Cys Asn Val Met Glu Pro Asn 165 170 175 caa aac aac tgg ctt cgt aca aac tgg atc tcc cgt gat gca gct cag 576 Gln Asn Asn Trp Leu Arg Thr Asn Trp Ile Ser Arg Asp Ala Ala Gln 180 185 190 aaa att tat gtg gaa atg aaa ttc aca cta agg gat tgt aac agc atc 624 Lys Ile Tyr Val Glu Met Lys Phe Thr Leu Arg Asp Cys Asn Ser Ile 195 200 205 cca tgg gtc ttg ggg act tgc aaa gaa aca ttt aat ctg ttt tat atg 672 Pro Trp Val Leu Gly Thr Cys Lys Glu Thr Phe Asn Leu Phe Tyr Met 210 215 220 gaa tca gat gag tcc cac gga att aaa ttc aag cca aac cag tat aca 720 Glu Ser Asp Glu Ser His Gly Ile Lys Phe Lys Pro Asn Gln Tyr Thr 225 230 235 240 aag atc gac aca att gct gct gat gag agt ttt acc cag atg gat ttg 768 Lys Ile Asp Thr Ile Ala Ala Asp Glu Ser Phe Thr Gln Met Asp Leu 245 250 255 ggt gat cgc atc ctc aaa ctc aac act gaa att cgt gag gtg ggg cct 816 Gly Asp Arg Ile Leu Lys Leu Asn Thr Glu Ile Arg Glu Val Gly Pro 260 265 270 ata gaa agg aaa gga ttt tat ctg gct ttt caa gac att ggg gcg tgc 864 Ile Glu Arg Lys Gly Phe Tyr Leu Ala Phe Gln Asp Ile Gly Ala Cys 275 280 285 att gcc ctg gtt tca gtc cgt gtt ttc tac aag aaa tgc ccc ttc act 912 Ile Ala Leu Val Ser Val Arg Val Phe Tyr Lys Lys Cys Pro Phe Thr 290 295 300 gtt cgt aac ttg gcc atg ttt cct gat acc att cca agg gtt gat tcc 960 Val Arg Asn Leu Ala Met Phe Pro Asp Thr Ile Pro Arg Val Asp Ser 305 310 315 320 tcc tct ttg gtt gaa gta cgg ggt tct tgt gtg aag agt gct gaa gag 1008 Ser Ser Leu Val Glu Val Arg Gly Ser Cys Val Lys Ser Ala Glu Glu 325 330 335 cgt gac act cct aaa ctg tat tgt gga gct gat gga gat tgg ctg gtt 1056 Arg Asp Thr Pro Lys Leu Tyr Cys Gly Ala Asp Gly Asp Trp Leu Val 340 345 350 cct ctt gga agg tgc atc tgc agt aca gga tat gaa gaa att gag ggt 1104 Pro Leu Gly Arg Cys Ile Cys Ser Thr Gly Tyr Glu Glu Ile Glu Gly 355 360 365 tct tgc cat gct tgc aga cca gga ttc tat aaa gct ttt gct ggg aac 1152 Ser Cys His Ala Cys Arg Pro Gly Phe Tyr Lys Ala Phe Ala Gly Asn 370 375 380 aca aaa tgt tct aaa tgt cct cca cac agt tta aca tac atg gaa gca 1200 Thr Lys Cys Ser Lys Cys Pro Pro His Ser Leu Thr Tyr Met Glu Ala 385 390 395 400 act tct gtc tgt cag tgt gaa aag ggt tat ttc cga gct gaa aaa gac 1248 Thr Ser Val Cys Gln Cys Glu Lys Gly Tyr Phe Arg Ala Glu Lys Asp 405 410 415 cca cct tct atg gca tgt acc agg cca cct tca gct cct agg aat gtg 1296 Pro Pro Ser Met Ala Cys Thr Arg Pro Pro Ser Ala Pro Arg Asn Val 420 425 430 gtt ttt aac atc aat gaa aca gcc ctt att ttg gaa tgg agc cca cca 1344 Val Phe Asn Ile Asn Glu Thr Ala Leu Ile Leu Glu Trp Ser Pro Pro 435 440 445 agt gac aca gga ggg aga aaa gat ctc aca tac agt gta atc tgt aag 1392 Ser Asp Thr Gly Gly Arg Lys Asp Leu Thr Tyr Ser Val Ile Cys Lys 450 455 460 aaa tgt ggc tta gac acc agc cag tgt gag gac tgt ggt gga gga ctc 1440 Lys Cys Gly Leu Asp Thr Ser Gln Cys Glu Asp Cys Gly Gly Gly Leu

465 470 475 480 cgc ttc atc cca aga cat aca ggc ctg atc aac aat tcc gtg ata gta 1488 Arg Phe Ile Pro Arg His Thr Gly Leu Ile Asn Asn Ser Val Ile Val 485 490 495 ctt gac ttt gtg tct cac gtg aat tac acc ttt gaa ata gaa gca atg 1536 Leu Asp Phe Val Ser His Val Asn Tyr Thr Phe Glu Ile Glu Ala Met 500 505 510 aat gga gtt tct gag ttg agt ttt tct ccc aag cca ttc aca gct att 1584 Asn Gly Val Ser Glu Leu Ser Phe Ser Pro Lys Pro Phe Thr Ala Ile 515 520 525 aca gtg acc acg gat caa gat gca cct tcc ctg ata ggt gtg gta agg 1632 Thr Val Thr Thr Asp Gln Asp Ala Pro Ser Leu Ile Gly Val Val Arg 530 535 540 aag gac tgg gca tcc caa aat agc att gcc cta tca tgg caa gca cct 1680 Lys Asp Trp Ala Ser Gln Asn Ser Ile Ala Leu Ser Trp Gln Ala Pro 545 550 555 560 gct ttt tcc aat gga gcc att ctg gac tac gag atc aag tac tat gag 1728 Ala Phe Ser Asn Gly Ala Ile Leu Asp Tyr Glu Ile Lys Tyr Tyr Glu 565 570 575 aag gaa cat gag cag ctg acc tac tct tcc aca agg tcc aaa gcc ccc 1776 Lys Glu His Glu Gln Leu Thr Tyr Ser Ser Thr Arg Ser Lys Ala Pro 580 585 590 agt gtc atc atc aca ggt ctt aag cca gcc acc aaa tat gta ttt cac 1824 Ser Val Ile Ile Thr Gly Leu Lys Pro Ala Thr Lys Tyr Val Phe His 595 600 605 atc cga gtg aga act gcg aca gga tac agt ggc tac agt cag aaa ttt 1872 Ile Arg Val Arg Thr Ala Thr Gly Tyr Ser Gly Tyr Ser Gln Lys Phe 610 615 620 gaa ttt gaa aca gga gat gaa act tct gac atg gca gca gaa caa gga 1920 Glu Phe Glu Thr Gly Asp Glu Thr Ser Asp Met Ala Ala Glu Gln Gly 625 630 635 640 cag att ctc gtg ata gcc acc gcc gct gtt ggc gga ttc act ctc ctc 1968 Gln Ile Leu Val Ile Ala Thr Ala Ala Val Gly Gly Phe Thr Leu Leu 645 650 655 gtc atc ctc act tta ttc ttc ttg atc act ggg aga tgt cag tgg tac 2016 Val Ile Leu Thr Leu Phe Phe Leu Ile Thr Gly Arg Cys Gln Trp Tyr 660 665 670 ata aaa gcc aag atg aag tca gaa gag aag aga aga aac cac tta cag 2064 Ile Lys Ala Lys Met Lys Ser Glu Glu Lys Arg Arg Asn His Leu Gln 675 680 685 aat ggg cat ttg cgc ttc ccg gga att aaa act tac att gat cca gat 2112 Asn Gly His Leu Arg Phe Pro Gly Ile Lys Thr Tyr Ile Asp Pro Asp 690 695 700 aca tat gaa gac cca tcc cta gca gtc cat gaa ttt gca aag gag att 2160 Thr Tyr Glu Asp Pro Ser Leu Ala Val His Glu Phe Ala Lys Glu Ile 705 710 715 720 gat ccc tca aga att cgt att gag aga gtc att ggg gca ggt gaa ttt 2208 Asp Pro Ser Arg Ile Arg Ile Glu Arg Val Ile Gly Ala Gly Glu Phe 725 730 735 gga gaa gtc tgt agt ggg cgt ttg aag aca cca ggg aaa aga gag atc 2256 Gly Glu Val Cys Ser Gly Arg Leu Lys Thr Pro Gly Lys Arg Glu Ile 740 745 750 cca gtt gcc att aaa act ttg aaa ggt ggc cac atg gat cgg caa aga 2304 Pro Val Ala Ile Lys Thr Leu Lys Gly Gly His Met Asp Arg Gln Arg 755 760 765 aga gat ttt cta aga gaa gct agt atc atg ggc cag ttt gac cat cca 2352 Arg Asp Phe Leu Arg Glu Ala Ser Ile Met Gly Gln Phe Asp His Pro 770 775 780 aac atc att cgc cta gaa ggg gtt gtc acc aaa aga tcc ttc ccg gcc 2400 Asn Ile Ile Arg Leu Glu Gly Val Val Thr Lys Arg Ser Phe Pro Ala 785 790 795 800 att ggg gtg gag gcg ttt tgc ccc agc ttc ctg agg gca ggg ttt tta 2448 Ile Gly Val Glu Ala Phe Cys Pro Ser Phe Leu Arg Ala Gly Phe Leu 805 810 815 aat agc atc cag gcc ccg cat cca gtg cca ggg gga gga tct ttg ccc 2496 Asn Ser Ile Gln Ala Pro His Pro Val Pro Gly Gly Gly Ser Leu Pro 820 825 830 ccc agg att cct gct ggc aga cca gta atg att gtg gtg gaa tat atg 2544 Pro Arg Ile Pro Ala Gly Arg Pro Val Met Ile Val Val Glu Tyr Met 835 840 845 gag aat gga tcc cta gac tcc ttt ttg cgg aag cat gat ggc cac ttc 2592 Glu Asn Gly Ser Leu Asp Ser Phe Leu Arg Lys His Asp Gly His Phe 850 855 860 aca gtc atc cag ttg gtc gga atg ctc cga ggc att gca tca ggc atg 2640 Thr Val Ile Gln Leu Val Gly Met Leu Arg Gly Ile Ala Ser Gly Met 865 870 875 880 aag tat ctt tct gat atg ggt tat gtt cat cga gac cta gcg gct cgg 2688 Lys Tyr Leu Ser Asp Met Gly Tyr Val His Arg Asp Leu Ala Ala Arg 885 890 895 aat ata ctg gtc aat agc aac tta gta tgc aaa gtt tct gat ttt ggt 2736 Asn Ile Leu Val Asn Ser Asn Leu Val Cys Lys Val Ser Asp Phe Gly 900 905 910 ctc tcc aga gtg ctg gaa gat gat cca gaa gct gct tat aca aca act 2784 Leu Ser Arg Val Leu Glu Asp Asp Pro Glu Ala Ala Tyr Thr Thr Thr 915 920 925 ggt gga aaa atc ccc ata agg tgg aca gcc cca gaa gcc atc gcc tac 2832 Gly Gly Lys Ile Pro Ile Arg Trp Thr Ala Pro Glu Ala Ile Ala Tyr 930 935 940 aga aaa ttc tcc tca gca agc gat gca tgg agc tat ggc att gtc atg 2880 Arg Lys Phe Ser Ser Ala Ser Asp Ala Trp Ser Tyr Gly Ile Val Met 945 950 955 960 tgg gag gtc atg tcc tat gga gag aga cct tat tgg gaa atg tct aac 2928 Trp Glu Val Met Ser Tyr Gly Glu Arg Pro Tyr Trp Glu Met Ser Asn 965 970 975 caa gat gtc att ctg tcc att gaa gaa ggg tac aga ctt cca gct ccc 2976 Gln Asp Val Ile Leu Ser Ile Glu Glu Gly Tyr Arg Leu Pro Ala Pro 980 985 990 atg ggc tgt cca gca tct cta cac cag ctg atg ctc cac tgc tgg cag 3024 Met Gly Cys Pro Ala Ser Leu His Gln Leu Met Leu His Cys Trp Gln 995 1000 1005 aag gag aga aat cac aga cca aaa ttt act gac att gtc agc ttc ctt 3072 Lys Glu Arg Asn His Arg Pro Lys Phe Thr Asp Ile Val Ser Phe Leu 1010 1015 1020 gac aaa ctg atc cga aat ccc agt gcc ctt cac acc ctg gtg gag gac 3120 Asp Lys Leu Ile Arg Asn Pro Ser Ala Leu His Thr Leu Val Glu Asp 1025 1030 1035 1040 atc ctt gta atg cca gag tcc cct ggt gaa gtt ccg gaa tat cct ttg 3168 Ile Leu Val Met Pro Glu Ser Pro Gly Glu Val Pro Glu Tyr Pro Leu 1045 1050 1055 ttt gtc aca gtt ggt gac tgg cta gat tct ata aag atg ggg caa tac 3216 Phe Val Thr Val Gly Asp Trp Leu Asp Ser Ile Lys Met Gly Gln Tyr 1060 1065 1070 aag aat aac ttc gtg gca gca ggg ttt aca aca ttt gac ctg att tca 3264 Lys Asn Asn Phe Val Ala Ala Gly Phe Thr Thr Phe Asp Leu Ile Ser 1075 1080 1085 aga atg agc att gat gac att aga aga att gga gtc ata ctt att gga 3312 Arg Met Ser Ile Asp Asp Ile Arg Arg Ile Gly Val Ile Leu Ile Gly 1090 1095 1100 cac cag aga cga ata gtc agc agc ata cag act tta cgt tta cac atg 3360 His Gln Arg Arg Ile Val Ser Ser Ile Gln Thr Leu Arg Leu His Met 1105 1110 1115 1120 atg cac ata cag gag aag gga ttt cat gta tga 3393 Met His Ile Gln Glu Lys Gly Phe His Val * 1125 1130 38 2466 DNA Homo sapiens CDS (437)...(1981) misc_feature (1)...(2466) n = A,T,C or G 38 gtccttctct aaggcgagct gcccttgggc gcgcctgggg ctgcacctgg gtcacgtggg 60 cgccgttgtg catgccggca cctcccggnc aaccccgcgg cttggagaag gggctttgca 120 cccgccgccg ctgtttgtcc tcgcgcggcc cccgtccact gccctgcggt tgctctgcgg 180 gctgaaaagt ttctcccggt gcagaattcc gggctcagcg acagcctgcg ccgagtgtgc 240 gcacctgtcg gagacccgcc agtccgccgg ccgcgctctc acgtgtgaat atgtgtctag 300 tgcatcctta acctgaggac ttcaccagtt cgaaattaca gttttcacca tcaactacct 360 tatccttttt ggtctggttt tcttcctcaa acagtggaaa catttttaaa gttgcttttg 420 ttgcagagtt aaacaa atg gct gat agt ggc tta gat aaa aaa tcc aca aaa 472 Met Ala Asp Ser Gly Leu Asp Lys Lys Ser Thr Lys 1 5 10 tgc ccc gac tgt tca tct gct tct cag aaa gat gta ctt tgt gta tgt 520 Cys Pro Asp Cys Ser Ser Ala Ser Gln Lys Asp Val Leu Cys Val Cys 15 20 25 tcc agc aaa aca agg gtt cct cca gtt ttg gtg gtg gaa atg tca cag 568 Ser Ser Lys Thr Arg Val Pro Pro Val Leu Val Val Glu Met Ser Gln 30 35 40 aca tca agc att ggt agt gca gaa tct tta att tca ctg gag aga aaa 616 Thr Ser Ser Ile Gly Ser Ala Glu Ser Leu Ile Ser Leu Glu Arg Lys 45 50 55 60 aaa gaa aaa aat atc aac aga gat ata acc tcc agg aaa gat ttg ccc 664 Lys Glu Lys Asn Ile Asn Arg Asp Ile Thr Ser Arg Lys Asp Leu Pro 65 70 75 tca aga acc tca aat gta gag aga aaa gca tct cag caa caa tgg ggt 712 Ser Arg Thr Ser Asn Val Glu Arg Lys Ala Ser Gln Gln Gln Trp Gly 80 85 90 cgg ggc aac ttt aca gaa gga aaa gtt cct cac ata agg att gag aat 760 Arg Gly Asn Phe Thr Glu Gly Lys Val Pro His Ile Arg Ile Glu Asn 95 100 105 gga gct gct att gag gaa atc tat acc ttt gga aga ata ttg gga aaa 808 Gly Ala Ala Ile Glu Glu Ile Tyr Thr Phe Gly Arg Ile Leu Gly Lys 110 115 120 ggg agc ttt gga ata gtc att gaa gcg aca gac aag gaa aca gaa acg 856 Gly Ser Phe Gly Ile Val Ile Glu Ala Thr Asp Lys Glu Thr Glu Thr 125 130 135 140 aag tgg gca att aaa aaa gtg aac aaa gaa aag gct gga agc tct gct 904 Lys Trp Ala Ile Lys Lys Val Asn Lys Glu Lys Ala Gly Ser Ser Ala 145 150 155 gtg aag tta ctt gaa cga gag gtg aac att ctg aaa agt gta aaa cat 952 Val Lys Leu Leu Glu Arg Glu Val Asn Ile Leu Lys Ser Val Lys His 160 165 170 gaa cac atc ata cat ctg gaa caa gta ttt gaa acg cca aag aaa atg 1000 Glu His Ile Ile His Leu Glu Gln Val Phe Glu Thr Pro Lys Lys Met 175 180 185 tac ctt gtg atg gag ctt tgt gag gat gga gaa ctc aaa gaa att ctg 1048 Tyr Leu Val Met Glu Leu Cys Glu Asp Gly Glu Leu Lys Glu Ile Leu 190 195 200 gat agg aaa ggg cat ttc tca gag aat gag aca agg tgg atc att caa 1096 Asp Arg Lys Gly His Phe Ser Glu Asn Glu Thr Arg Trp Ile Ile Gln 205 210 215 220 agt ctc gca tca gct ata gca tat ctt cac aat aat gat att gta cat 1144 Ser Leu Ala Ser Ala Ile Ala Tyr Leu His Asn Asn Asp Ile Val His 225 230 235 aga gat ctg aaa ctg gaa aat ata atg gtt aaa agc agt ctt att gat 1192 Arg Asp Leu Lys Leu Glu Asn Ile Met Val Lys Ser Ser Leu Ile Asp 240 245 250 gat aac aat gaa ata aac tta aac ata aag gtg act gat ttt ggc tta 1240 Asp Asn Asn Glu Ile Asn Leu Asn Ile Lys Val Thr Asp Phe Gly Leu 255 260 265 gcg gtg aag aag caa agt agg agt gaa gcc atg ctg cag gcc aca tgt 1288 Ala Val Lys Lys Gln Ser Arg Ser Glu Ala Met Leu Gln Ala Thr Cys 270 275 280 ggg act cct atc tat atg gcc cct gaa gtt atc agt gcc cac gac tat 1336 Gly Thr Pro Ile Tyr Met Ala Pro Glu Val Ile Ser Ala His Asp Tyr 285 290 295 300 agc cag cag tgt gac att tgg agc ata ggc gtc gta atg tac atg tta 1384 Ser Gln Gln Cys Asp Ile Trp Ser Ile Gly Val Val Met Tyr Met Leu 305 310 315 tta cgt gga gaa cca ccc ttt ttg gca agc tca gaa gag aag ctt ttt 1432 Leu Arg Gly Glu Pro Pro Phe Leu Ala Ser Ser Glu Glu Lys Leu Phe 320 325 330 gag tta ata aga aaa gga gaa cta cat ttt gaa aat gca gtc tgg aat 1480 Glu Leu Ile Arg Lys Gly Glu Leu His Phe Glu Asn Ala Val Trp Asn 335 340 345 tcc ata agt gac tgt gct aaa agt gtt ttg aaa caa ctt atg aaa gta 1528 Ser Ile Ser Asp Cys Ala Lys Ser Val Leu Lys Gln Leu Met Lys Val 350 355 360 gat cct gct cac aga atc aca gct aag gaa cta cta gat aac cag tgg 1576 Asp Pro Ala His Arg Ile Thr Ala Lys Glu Leu Leu Asp Asn Gln Trp 365 370 375 380 tta aca ggc aat aaa ctt tct tcg gtg aga cca acc aat gta tta gag 1624 Leu Thr Gly Asn Lys Leu Ser Ser Val Arg Pro Thr Asn Val Leu Glu 385 390 395 atg atg aag gaa tgg aaa aat aac cca gaa agt gtt gag gaa aac aca 1672 Met Met Lys Glu Trp Lys Asn Asn Pro Glu Ser Val Glu Glu Asn Thr 400 405 410 aca gaa gag aag aat aag ccg tcc act gaa gaa aag ttg aaa agt tac 1720 Thr Glu Glu Lys Asn Lys Pro Ser Thr Glu Glu Lys Leu Lys Ser Tyr 415 420 425 caa ccc tgg gga aat gtc cct gat gcc aat tac act tca gat gaa gag 1768 Gln Pro Trp Gly Asn Val Pro Asp Ala Asn Tyr Thr Ser Asp Glu Glu 430 435 440 gag gaa aaa cag tct act gct tat gaa aag caa ttt cct gca acc agt 1816 Glu Glu Lys Gln Ser Thr Ala Tyr Glu Lys Gln Phe Pro Ala Thr Ser 445 450 455 460 aag gac aac ttt gat atg tgc agt tca agt ttc aca tct agc aaa ctc 1864 Lys Asp Asn Phe Asp Met Cys Ser Ser Ser Phe Thr Ser Ser Lys Leu 465 470 475 ctt cca gct gaa atc aag gga gaa atg gag aaa acc cct gtg act cca 1912 Leu Pro Ala Glu Ile Lys Gly Glu Met Glu Lys Thr Pro Val Thr Pro 480 485 490 agc caa gga aca gca acc aag tac cct gct aaa tcc ggc gcc ctg tcc 1960 Ser Gln Gly Thr Ala Thr Lys Tyr Pro Ala Lys Ser Gly Ala Leu Ser 495 500 505 aga acc aaa aag aaa ctc taa ggttccctcc agtgttggac agtacaaaaa 2011 Arg Thr Lys Lys Lys Leu * 510 caaagctgct cttgttagca ctttgatgag ggggtaggag gggaagaaga cagccctatg 2071 ctgagcttgt agccttttag ctccacagag ccccgccatg tgtttgcacc agcttaaaat 2131 tgaagctgct tatctccaaa gcagcataag ctgcacatgg cattaaagga cagccaccag 2191 taggcttggc agtgggctgc agtggaaatc aactcaagat gtacacgaag gttttttagg 2251 ggggcagata ccttcaattt aaggctgtgg gcacacttgc tcatttttac ttcaaattct 2311 tatgtttagg cacagctatt tataggggaa aacaagaggc caaatatagt aatggaggtg 2371 ccaaataatt atgtgcactt tgcactagaa gactttgtta gaaaattact aataaacttg 2431 ccatacgtat tacaaaaaaa aaaaaaaaaa aaaaa 2466 39 514 PRT Homo sapiens 39 Met Ala Asp Ser Gly Leu Asp Lys Lys Ser Thr Lys Cys Pro Asp Cys 1 5 10 15 Ser Ser Ala Ser Gln Lys Asp Val Leu Cys Val Cys Ser Ser Lys Thr 20 25 30 Arg Val Pro Pro Val Leu Val Val Glu Met Ser Gln Thr Ser Ser Ile 35 40 45 Gly Ser Ala Glu Ser Leu Ile Ser Leu Glu Arg Lys Lys Glu Lys Asn 50 55 60 Ile Asn Arg Asp Ile Thr Ser Arg Lys Asp Leu Pro Ser Arg Thr Ser 65 70 75 80 Asn Val Glu Arg Lys Ala Ser Gln Gln Gln Trp Gly Arg Gly Asn Phe 85 90 95 Thr Glu Gly Lys Val Pro His Ile Arg Ile Glu Asn Gly Ala Ala Ile 100 105 110 Glu Glu Ile Tyr Thr Phe Gly Arg Ile Leu Gly Lys Gly Ser Phe Gly 115 120 125 Ile Val Ile Glu Ala Thr Asp Lys Glu Thr Glu Thr Lys Trp Ala Ile 130 135 140 Lys Lys Val Asn Lys Glu Lys Ala Gly Ser Ser Ala Val Lys Leu Leu 145 150 155 160 Glu Arg Glu Val Asn Ile Leu Lys Ser Val Lys His Glu His Ile Ile 165 170 175 His Leu Glu Gln Val Phe Glu Thr Pro Lys Lys Met Tyr Leu Val Met 180 185 190 Glu Leu Cys Glu Asp Gly Glu Leu Lys Glu Ile Leu Asp Arg Lys Gly 195 200 205 His Phe Ser Glu Asn Glu Thr Arg Trp Ile Ile Gln Ser Leu Ala Ser 210 215 220 Ala Ile Ala Tyr Leu His Asn Asn Asp Ile Val His Arg Asp Leu Lys 225 230 235 240 Leu Glu Asn Ile Met Val Lys Ser Ser Leu Ile Asp Asp Asn Asn Glu 245 250 255 Ile Asn Leu Asn Ile Lys Val Thr Asp Phe Gly Leu Ala Val Lys Lys 260 265 270 Gln Ser Arg Ser Glu Ala Met Leu Gln Ala Thr Cys Gly Thr Pro Ile 275 280 285 Tyr Met Ala Pro Glu Val Ile Ser Ala His Asp Tyr Ser Gln Gln Cys 290 295 300 Asp Ile Trp Ser Ile Gly Val Val Met Tyr Met Leu Leu Arg Gly Glu 305 310 315 320 Pro Pro Phe Leu Ala Ser Ser Glu Glu Lys Leu Phe Glu Leu Ile Arg 325 330 335 Lys Gly Glu Leu His Phe Glu Asn Ala Val Trp Asn Ser Ile Ser Asp 340 345 350 Cys Ala Lys Ser Val Leu Lys Gln Leu Met Lys Val Asp Pro Ala His 355 360 365 Arg Ile Thr Ala Lys Glu Leu Leu Asp Asn Gln Trp Leu Thr Gly Asn 370 375 380 Lys Leu Ser Ser Val

Arg Pro Thr Asn Val Leu Glu Met Met Lys Glu 385 390 395 400 Trp Lys Asn Asn Pro Glu Ser Val Glu Glu Asn Thr Thr Glu Glu Lys 405 410 415 Asn Lys Pro Ser Thr Glu Glu Lys Leu Lys Ser Tyr Gln Pro Trp Gly 420 425 430 Asn Val Pro Asp Ala Asn Tyr Thr Ser Asp Glu Glu Glu Glu Lys Gln 435 440 445 Ser Thr Ala Tyr Glu Lys Gln Phe Pro Ala Thr Ser Lys Asp Asn Phe 450 455 460 Asp Met Cys Ser Ser Ser Phe Thr Ser Ser Lys Leu Leu Pro Ala Glu 465 470 475 480 Ile Lys Gly Glu Met Glu Lys Thr Pro Val Thr Pro Ser Gln Gly Thr 485 490 495 Ala Thr Lys Tyr Pro Ala Lys Ser Gly Ala Leu Ser Arg Thr Lys Lys 500 505 510 Lys Leu 40 1545 DNA Homo sapiens CDS (1)...(1545) 40 atg gct gat agt ggc tta gat aaa aaa tcc aca aaa tgc ccc gac tgt 48 Met Ala Asp Ser Gly Leu Asp Lys Lys Ser Thr Lys Cys Pro Asp Cys 1 5 10 15 tca tct gct tct cag aaa gat gta ctt tgt gta tgt tcc agc aaa aca 96 Ser Ser Ala Ser Gln Lys Asp Val Leu Cys Val Cys Ser Ser Lys Thr 20 25 30 agg gtt cct cca gtt ttg gtg gtg gaa atg tca cag aca tca agc att 144 Arg Val Pro Pro Val Leu Val Val Glu Met Ser Gln Thr Ser Ser Ile 35 40 45 ggt agt gca gaa tct tta att tca ctg gag aga aaa aaa gaa aaa aat 192 Gly Ser Ala Glu Ser Leu Ile Ser Leu Glu Arg Lys Lys Glu Lys Asn 50 55 60 atc aac aga gat ata acc tcc agg aaa gat ttg ccc tca aga acc tca 240 Ile Asn Arg Asp Ile Thr Ser Arg Lys Asp Leu Pro Ser Arg Thr Ser 65 70 75 80 aat gta gag aga aaa gca tct cag caa caa tgg ggt cgg ggc aac ttt 288 Asn Val Glu Arg Lys Ala Ser Gln Gln Gln Trp Gly Arg Gly Asn Phe 85 90 95 aca gaa gga aaa gtt cct cac ata agg att gag aat gga gct gct att 336 Thr Glu Gly Lys Val Pro His Ile Arg Ile Glu Asn Gly Ala Ala Ile 100 105 110 gag gaa atc tat acc ttt gga aga ata ttg gga aaa ggg agc ttt gga 384 Glu Glu Ile Tyr Thr Phe Gly Arg Ile Leu Gly Lys Gly Ser Phe Gly 115 120 125 ata gtc att gaa gcg aca gac aag gaa aca gaa acg aag tgg gca att 432 Ile Val Ile Glu Ala Thr Asp Lys Glu Thr Glu Thr Lys Trp Ala Ile 130 135 140 aaa aaa gtg aac aaa gaa aag gct gga agc tct gct gtg aag tta ctt 480 Lys Lys Val Asn Lys Glu Lys Ala Gly Ser Ser Ala Val Lys Leu Leu 145 150 155 160 gaa cga gag gtg aac att ctg aaa agt gta aaa cat gaa cac atc ata 528 Glu Arg Glu Val Asn Ile Leu Lys Ser Val Lys His Glu His Ile Ile 165 170 175 cat ctg gaa caa gta ttt gaa acg cca aag aaa atg tac ctt gtg atg 576 His Leu Glu Gln Val Phe Glu Thr Pro Lys Lys Met Tyr Leu Val Met 180 185 190 gag ctt tgt gag gat gga gaa ctc aaa gaa att ctg gat agg aaa ggg 624 Glu Leu Cys Glu Asp Gly Glu Leu Lys Glu Ile Leu Asp Arg Lys Gly 195 200 205 cat ttc tca gag aat gag aca agg tgg atc att caa agt ctc gca tca 672 His Phe Ser Glu Asn Glu Thr Arg Trp Ile Ile Gln Ser Leu Ala Ser 210 215 220 gct ata gca tat ctt cac aat aat gat att gta cat aga gat ctg aaa 720 Ala Ile Ala Tyr Leu His Asn Asn Asp Ile Val His Arg Asp Leu Lys 225 230 235 240 ctg gaa aat ata atg gtt aaa agc agt ctt att gat gat aac aat gaa 768 Leu Glu Asn Ile Met Val Lys Ser Ser Leu Ile Asp Asp Asn Asn Glu 245 250 255 ata aac tta aac ata aag gtg act gat ttt ggc tta gcg gtg aag aag 816 Ile Asn Leu Asn Ile Lys Val Thr Asp Phe Gly Leu Ala Val Lys Lys 260 265 270 caa agt agg agt gaa gcc atg ctg cag gcc aca tgt ggg act cct atc 864 Gln Ser Arg Ser Glu Ala Met Leu Gln Ala Thr Cys Gly Thr Pro Ile 275 280 285 tat atg gcc cct gaa gtt atc agt gcc cac gac tat agc cag cag tgt 912 Tyr Met Ala Pro Glu Val Ile Ser Ala His Asp Tyr Ser Gln Gln Cys 290 295 300 gac att tgg agc ata ggc gtc gta atg tac atg tta tta cgt gga gaa 960 Asp Ile Trp Ser Ile Gly Val Val Met Tyr Met Leu Leu Arg Gly Glu 305 310 315 320 cca ccc ttt ttg gca agc tca gaa gag aag ctt ttt gag tta ata aga 1008 Pro Pro Phe Leu Ala Ser Ser Glu Glu Lys Leu Phe Glu Leu Ile Arg 325 330 335 aaa gga gaa cta cat ttt gaa aat gca gtc tgg aat tcc ata agt gac 1056 Lys Gly Glu Leu His Phe Glu Asn Ala Val Trp Asn Ser Ile Ser Asp 340 345 350 tgt gct aaa agt gtt ttg aaa caa ctt atg aaa gta gat cct gct cac 1104 Cys Ala Lys Ser Val Leu Lys Gln Leu Met Lys Val Asp Pro Ala His 355 360 365 aga atc aca gct aag gaa cta cta gat aac cag tgg tta aca ggc aat 1152 Arg Ile Thr Ala Lys Glu Leu Leu Asp Asn Gln Trp Leu Thr Gly Asn 370 375 380 aaa ctt tct tcg gtg aga cca acc aat gta tta gag atg atg aag gaa 1200 Lys Leu Ser Ser Val Arg Pro Thr Asn Val Leu Glu Met Met Lys Glu 385 390 395 400 tgg aaa aat aac cca gaa agt gtt gag gaa aac aca aca gaa gag aag 1248 Trp Lys Asn Asn Pro Glu Ser Val Glu Glu Asn Thr Thr Glu Glu Lys 405 410 415 aat aag ccg tcc act gaa gaa aag ttg aaa agt tac caa ccc tgg gga 1296 Asn Lys Pro Ser Thr Glu Glu Lys Leu Lys Ser Tyr Gln Pro Trp Gly 420 425 430 aat gtc cct gat gcc aat tac act tca gat gaa gag gag gaa aaa cag 1344 Asn Val Pro Asp Ala Asn Tyr Thr Ser Asp Glu Glu Glu Glu Lys Gln 435 440 445 tct act gct tat gaa aag caa ttt cct gca acc agt aag gac aac ttt 1392 Ser Thr Ala Tyr Glu Lys Gln Phe Pro Ala Thr Ser Lys Asp Asn Phe 450 455 460 gat atg tgc agt tca agt ttc aca tct agc aaa ctc ctt cca gct gaa 1440 Asp Met Cys Ser Ser Ser Phe Thr Ser Ser Lys Leu Leu Pro Ala Glu 465 470 475 480 atc aag gga gaa atg gag aaa acc cct gtg act cca agc caa gga aca 1488 Ile Lys Gly Glu Met Glu Lys Thr Pro Val Thr Pro Ser Gln Gly Thr 485 490 495 gca acc aag tac cct gct aaa tcc ggc gcc ctg tcc aga acc aaa aag 1536 Ala Thr Lys Tyr Pro Ala Lys Ser Gly Ala Leu Ser Arg Thr Lys Lys 500 505 510 aaa ctc taa 1545 Lys Leu * 41 2711 DNA Homo sapiens CDS (198)...(1883) misc_feature (1)...(2711) n = A,T,C or G 41 cgcgtccgaa aaaaaaaaaa aaaaaaaaaa aangggctgn gctcsrcgmt yccggcccca 60 gcgaggcggt ggggcggggc ggggcggggc ggggcgcgca gcaggagcga gtggggccgc 120 cgccgggccg cggacactgt cgcccggcgc ccaggttccc aacaaggcta cgcagaagaa 180 cccccttgac tgaagca atg gag ggg ggt cca gct gtc tgc tgc cag gat 230 Met Glu Gly Gly Pro Ala Val Cys Cys Gln Asp 1 5 10 cct cgg gca gag ctg gta gaa cgg gtg gca gcc atc gat gtg act cac 278 Pro Arg Ala Glu Leu Val Glu Arg Val Ala Ala Ile Asp Val Thr His 15 20 25 ttg gag gag gca gat ggt ggc cca gag cct act aga aac ggt gtg gac 326 Leu Glu Glu Ala Asp Gly Gly Pro Glu Pro Thr Arg Asn Gly Val Asp 30 35 40 ccc cca cca cgg gcc aga gct gcc tct gtg atc cct ggc agt act tca 374 Pro Pro Pro Arg Ala Arg Ala Ala Ser Val Ile Pro Gly Ser Thr Ser 45 50 55 aga ctg ctc cca gcc cgg cct agc ctc tca gcc agg aag ctt tcc cta 422 Arg Leu Leu Pro Ala Arg Pro Ser Leu Ser Ala Arg Lys Leu Ser Leu 60 65 70 75 cag gag cgg cca gca gga agc tat ctg gag gcg cag gct ggg cct tat 470 Gln Glu Arg Pro Ala Gly Ser Tyr Leu Glu Ala Gln Ala Gly Pro Tyr 80 85 90 gcc acg ggg cct gcc agc cac atc tcc ccc cgg gcc tgg cgg agg ccc 518 Ala Thr Gly Pro Ala Ser His Ile Ser Pro Arg Ala Trp Arg Arg Pro 95 100 105 acc atc gag tcc cac cac gtg gcc atc tca gat gca gag gac tgc gtg 566 Thr Ile Glu Ser His His Val Ala Ile Ser Asp Ala Glu Asp Cys Val 110 115 120 cag ctg aac cag tac aag ctg cag agt gag att ggc aag ggt gcc tac 614 Gln Leu Asn Gln Tyr Lys Leu Gln Ser Glu Ile Gly Lys Gly Ala Tyr 125 130 135 ggt gtg gtg agg ctg gcc tac aac gaa agt gaa gac aga cac tat gca 662 Gly Val Val Arg Leu Ala Tyr Asn Glu Ser Glu Asp Arg His Tyr Ala 140 145 150 155 atg aaa gtc ctt tcc aaa aag aag tta ctg aag cag tat ggc ttt cca 710 Met Lys Val Leu Ser Lys Lys Lys Leu Leu Lys Gln Tyr Gly Phe Pro 160 165 170 cgt cgc cct ccc cca aga ggg tcc cag gct gcc cag gga gga cca gcc 758 Arg Arg Pro Pro Pro Arg Gly Ser Gln Ala Ala Gln Gly Gly Pro Ala 175 180 185 aag cag ctg ctg ccc ctg gag cgg gtg tac cag gag att gcc atc ctg 806 Lys Gln Leu Leu Pro Leu Glu Arg Val Tyr Gln Glu Ile Ala Ile Leu 190 195 200 aag aag ctg gac cac gtg aat gtg gtc aaa ctg atc gag gtc ctg gat 854 Lys Lys Leu Asp His Val Asn Val Val Lys Leu Ile Glu Val Leu Asp 205 210 215 gac cca gct gag gac aac ctc tat ttg gtg ttt gac ctc ctg aga aag 902 Asp Pro Ala Glu Asp Asn Leu Tyr Leu Val Phe Asp Leu Leu Arg Lys 220 225 230 235 ggg ccc gtc atg gaa gtg ccc tgt gac aag ccc ttc tcg gag gag caa 950 Gly Pro Val Met Glu Val Pro Cys Asp Lys Pro Phe Ser Glu Glu Gln 240 245 250 gct cgc ctc tac ctg cgg gac gtc atc ctg ggc ctc gag tac ttg cac 998 Ala Arg Leu Tyr Leu Arg Asp Val Ile Leu Gly Leu Glu Tyr Leu His 255 260 265 tgc cag aag atc gtc cac agg gac atc aag cca tcc aac ctg ctc ctg 1046 Cys Gln Lys Ile Val His Arg Asp Ile Lys Pro Ser Asn Leu Leu Leu 270 275 280 ggg gat gat ggg cac gtg aag atc gcc gac ttt ggc gtc agc aac cag 1094 Gly Asp Asp Gly His Val Lys Ile Ala Asp Phe Gly Val Ser Asn Gln 285 290 295 ttt gag ggg aac gac gct cag ctg tcc agc acg gcg gga acc cca gca 1142 Phe Glu Gly Asn Asp Ala Gln Leu Ser Ser Thr Ala Gly Thr Pro Ala 300 305 310 315 ttc atg gcc ccc gag gcc att tct gat tcc ggc cag agc ttc agt ggg 1190 Phe Met Ala Pro Glu Ala Ile Ser Asp Ser Gly Gln Ser Phe Ser Gly 320 325 330 aag gcc ttg gat gta tgg gcc act ggc gtc acg ttg tac tgc ttt gtc 1238 Lys Ala Leu Asp Val Trp Ala Thr Gly Val Thr Leu Tyr Cys Phe Val 335 340 345 tat ggg aag tgc ccg ttc atc gac gat ttc atc ctg gcc ctc cac agg 1286 Tyr Gly Lys Cys Pro Phe Ile Asp Asp Phe Ile Leu Ala Leu His Arg 350 355 360 aag atc aag aat gag ccc gtg gtg ttt cct gag ggg cca gaa atc agc 1334 Lys Ile Lys Asn Glu Pro Val Val Phe Pro Glu Gly Pro Glu Ile Ser 365 370 375 gag gag ctc aag gac ctg atc ctg aag atg tta gac aag aat ccc gag 1382 Glu Glu Leu Lys Asp Leu Ile Leu Lys Met Leu Asp Lys Asn Pro Glu 380 385 390 395 acg aga att ggg gtg cca gac atc aag ttg cac cct tgg gtg acc aag 1430 Thr Arg Ile Gly Val Pro Asp Ile Lys Leu His Pro Trp Val Thr Lys 400 405 410 aac ggg gag gag ccc ctt cct tcg gag gag gag cac tgc agc gtg gtg 1478 Asn Gly Glu Glu Pro Leu Pro Ser Glu Glu Glu His Cys Ser Val Val 415 420 425 gag gtg aca gag gag gag gtt aag aac tca gtc agg ctc atc ccc agc 1526 Glu Val Thr Glu Glu Glu Val Lys Asn Ser Val Arg Leu Ile Pro Ser 430 435 440 tgg acc acg gtg atc ctg gtg aag tcc atg ctg agg aag cgt tcc ttt 1574 Trp Thr Thr Val Ile Leu Val Lys Ser Met Leu Arg Lys Arg Ser Phe 445 450 455 ggg aac ccg ttt gag ccc caa gca cgg agg gaa gag cga tcc atg tct 1622 Gly Asn Pro Phe Glu Pro Gln Ala Arg Arg Glu Glu Arg Ser Met Ser 460 465 470 475 gct cca gga aac cta ctg gtg aaa gaa ggg ttt ggt gaa ggg ggc aag 1670 Ala Pro Gly Asn Leu Leu Val Lys Glu Gly Phe Gly Glu Gly Gly Lys 480 485 490 agc cca gag ctc ccc ggc gtc cag gct tac cac aac gga aga gac ctc 1718 Ser Pro Glu Leu Pro Gly Val Gln Ala Tyr His Asn Gly Arg Asp Leu 495 500 505 ccg ctg ggg ccg ggc agg cct ggc tca gct gcc aca ggc ata tgg tgg 1766 Pro Leu Gly Pro Gly Arg Pro Gly Ser Ala Ala Thr Gly Ile Trp Trp 510 515 520 aga ggg ggg tac cct gcc cac ctt ggg gtg gtg gca cca gag ctc ttg 1814 Arg Gly Gly Tyr Pro Ala His Leu Gly Val Val Ala Pro Glu Leu Leu 525 530 535 tct att cag acg ctg gta tgg ggg ctc gga ccc ctc act ggg gac agg 1862 Ser Ile Gln Thr Leu Val Trp Gly Leu Gly Pro Leu Thr Gly Asp Arg 540 545 550 555 gcc agt gtt gga gaa ttc tga ttcctttttt gttgtctttt acttttgttt 1913 Ala Ser Val Gly Glu Phe * 560 ttaacctggg ggttcgggga gaggccctgc ttgggaacat ctcacgagct ttcctacatc 1973 ttccgtggtt cccagcacag cccaagatta tttggcagcc aagtggatgg aactaacttt 2033 cctggactgt gtttcgcatt cggcgttatc tggaaagtgg actgaacgga atcaagctct 2093 gagcagaggc ctgaagcgga agcaccacat cgtccctgcc catctcactc tctcccttga 2153 tgatgcccct agagctgagg ctggagaaga caccagggct gactttgacc gagggccatg 2213 gacgcgacag gcctgtggcc ctgcgcatgc tgaaataact ggaacccagc ctctcctcct 2273 acaccggcct acccatctgg gcccaagagc tgcactcaca ctcctacaac gaaggacaaa 2333 ctgtccaggt cggagggatc acgagacaca gaacctggag gggtgtgcac gctggcaggt 2393 ggcctctgcg gcaattgcct caccctgagg acatcagcag tcagcctgct tcagaagcgg 2453 nggtgctgga gcgccgtgca gacacaagct ttttcggagc aggccttcac cttctctntg 2513 ggatcaagtg tcccggctgg cccgacgtgg catttgctga cccgaatgct tatagaggtt 2573 gacccccaac agggtcaccg cangactcgg gacactgccc tggaaaacat ggatggacaa 2633 ggggcttttg gccacaggtg tgggtgtcct gttggaggan ggctttgttt ggagaangga 2693 ggcttgctgg gggagaaa 2711 42 561 PRT Homo sapiens 42 Met Glu Gly Gly Pro Ala Val Cys Cys Gln Asp Pro Arg Ala Glu Leu 1 5 10 15 Val Glu Arg Val Ala Ala Ile Asp Val Thr His Leu Glu Glu Ala Asp 20 25 30 Gly Gly Pro Glu Pro Thr Arg Asn Gly Val Asp Pro Pro Pro Arg Ala 35 40 45 Arg Ala Ala Ser Val Ile Pro Gly Ser Thr Ser Arg Leu Leu Pro Ala 50 55 60 Arg Pro Ser Leu Ser Ala Arg Lys Leu Ser Leu Gln Glu Arg Pro Ala 65 70 75 80 Gly Ser Tyr Leu Glu Ala Gln Ala Gly Pro Tyr Ala Thr Gly Pro Ala 85 90 95 Ser His Ile Ser Pro Arg Ala Trp Arg Arg Pro Thr Ile Glu Ser His 100 105 110 His Val Ala Ile Ser Asp Ala Glu Asp Cys Val Gln Leu Asn Gln Tyr 115 120 125 Lys Leu Gln Ser Glu Ile Gly Lys Gly Ala Tyr Gly Val Val Arg Leu 130 135 140 Ala Tyr Asn Glu Ser Glu Asp Arg His Tyr Ala Met Lys Val Leu Ser 145 150 155 160 Lys Lys Lys Leu Leu Lys Gln Tyr Gly Phe Pro Arg Arg Pro Pro Pro 165 170 175 Arg Gly Ser Gln Ala Ala Gln Gly Gly Pro Ala Lys Gln Leu Leu Pro 180 185 190 Leu Glu Arg Val Tyr Gln Glu Ile Ala Ile Leu Lys Lys Leu Asp His 195 200 205 Val Asn Val Val Lys Leu Ile Glu Val Leu Asp Asp Pro Ala Glu Asp 210 215 220 Asn Leu Tyr Leu Val Phe Asp Leu Leu Arg Lys Gly Pro Val Met Glu 225 230 235 240 Val Pro Cys Asp Lys Pro Phe Ser Glu Glu Gln Ala Arg Leu Tyr Leu 245 250 255 Arg Asp Val Ile Leu Gly Leu Glu Tyr Leu His Cys Gln Lys Ile Val 260 265 270 His Arg Asp Ile Lys Pro Ser Asn Leu Leu Leu Gly Asp Asp Gly His 275 280 285 Val Lys Ile Ala Asp Phe Gly Val Ser Asn Gln Phe Glu Gly Asn Asp 290 295 300 Ala Gln Leu Ser Ser Thr Ala Gly Thr Pro Ala Phe Met Ala Pro Glu 305 310 315 320 Ala Ile Ser Asp Ser Gly Gln Ser Phe Ser Gly Lys Ala Leu Asp Val 325 330 335 Trp Ala Thr Gly Val Thr Leu Tyr Cys Phe Val Tyr Gly Lys Cys Pro 340 345 350 Phe Ile Asp Asp Phe Ile Leu Ala Leu His Arg Lys Ile Lys Asn Glu 355 360 365 Pro Val Val Phe Pro Glu Gly Pro Glu Ile Ser Glu Glu Leu Lys Asp 370 375

380 Leu Ile Leu Lys Met Leu Asp Lys Asn Pro Glu Thr Arg Ile Gly Val 385 390 395 400 Pro Asp Ile Lys Leu His Pro Trp Val Thr Lys Asn Gly Glu Glu Pro 405 410 415 Leu Pro Ser Glu Glu Glu His Cys Ser Val Val Glu Val Thr Glu Glu 420 425 430 Glu Val Lys Asn Ser Val Arg Leu Ile Pro Ser Trp Thr Thr Val Ile 435 440 445 Leu Val Lys Ser Met Leu Arg Lys Arg Ser Phe Gly Asn Pro Phe Glu 450 455 460 Pro Gln Ala Arg Arg Glu Glu Arg Ser Met Ser Ala Pro Gly Asn Leu 465 470 475 480 Leu Val Lys Glu Gly Phe Gly Glu Gly Gly Lys Ser Pro Glu Leu Pro 485 490 495 Gly Val Gln Ala Tyr His Asn Gly Arg Asp Leu Pro Leu Gly Pro Gly 500 505 510 Arg Pro Gly Ser Ala Ala Thr Gly Ile Trp Trp Arg Gly Gly Tyr Pro 515 520 525 Ala His Leu Gly Val Val Ala Pro Glu Leu Leu Ser Ile Gln Thr Leu 530 535 540 Val Trp Gly Leu Gly Pro Leu Thr Gly Asp Arg Ala Ser Val Gly Glu 545 550 555 560 Phe 43 1686 DNA Homo sapiens CDS (1)...(1686) 43 atg gag ggg ggt cca gct gtc tgc tgc cag gat cct cgg gca gag ctg 48 Met Glu Gly Gly Pro Ala Val Cys Cys Gln Asp Pro Arg Ala Glu Leu 1 5 10 15 gta gaa cgg gtg gca gcc atc gat gtg act cac ttg gag gag gca gat 96 Val Glu Arg Val Ala Ala Ile Asp Val Thr His Leu Glu Glu Ala Asp 20 25 30 ggt ggc cca gag cct act aga aac ggt gtg gac ccc cca cca cgg gcc 144 Gly Gly Pro Glu Pro Thr Arg Asn Gly Val Asp Pro Pro Pro Arg Ala 35 40 45 aga gct gcc tct gtg atc cct ggc agt act tca aga ctg ctc cca gcc 192 Arg Ala Ala Ser Val Ile Pro Gly Ser Thr Ser Arg Leu Leu Pro Ala 50 55 60 cgg cct agc ctc tca gcc agg aag ctt tcc cta cag gag cgg cca gca 240 Arg Pro Ser Leu Ser Ala Arg Lys Leu Ser Leu Gln Glu Arg Pro Ala 65 70 75 80 gga agc tat ctg gag gcg cag gct ggg cct tat gcc acg ggg cct gcc 288 Gly Ser Tyr Leu Glu Ala Gln Ala Gly Pro Tyr Ala Thr Gly Pro Ala 85 90 95 agc cac atc tcc ccc cgg gcc tgg cgg agg ccc acc atc gag tcc cac 336 Ser His Ile Ser Pro Arg Ala Trp Arg Arg Pro Thr Ile Glu Ser His 100 105 110 cac gtg gcc atc tca gat gca gag gac tgc gtg cag ctg aac cag tac 384 His Val Ala Ile Ser Asp Ala Glu Asp Cys Val Gln Leu Asn Gln Tyr 115 120 125 aag ctg cag agt gag att ggc aag ggt gcc tac ggt gtg gtg agg ctg 432 Lys Leu Gln Ser Glu Ile Gly Lys Gly Ala Tyr Gly Val Val Arg Leu 130 135 140 gcc tac aac gaa agt gaa gac aga cac tat gca atg aaa gtc ctt tcc 480 Ala Tyr Asn Glu Ser Glu Asp Arg His Tyr Ala Met Lys Val Leu Ser 145 150 155 160 aaa aag aag tta ctg aag cag tat ggc ttt cca cgt cgc cct ccc cca 528 Lys Lys Lys Leu Leu Lys Gln Tyr Gly Phe Pro Arg Arg Pro Pro Pro 165 170 175 aga ggg tcc cag gct gcc cag gga gga cca gcc aag cag ctg ctg ccc 576 Arg Gly Ser Gln Ala Ala Gln Gly Gly Pro Ala Lys Gln Leu Leu Pro 180 185 190 ctg gag cgg gtg tac cag gag att gcc atc ctg aag aag ctg gac cac 624 Leu Glu Arg Val Tyr Gln Glu Ile Ala Ile Leu Lys Lys Leu Asp His 195 200 205 gtg aat gtg gtc aaa ctg atc gag gtc ctg gat gac cca gct gag gac 672 Val Asn Val Val Lys Leu Ile Glu Val Leu Asp Asp Pro Ala Glu Asp 210 215 220 aac ctc tat ttg gtg ttt gac ctc ctg aga aag ggg ccc gtc atg gaa 720 Asn Leu Tyr Leu Val Phe Asp Leu Leu Arg Lys Gly Pro Val Met Glu 225 230 235 240 gtg ccc tgt gac aag ccc ttc tcg gag gag caa gct cgc ctc tac ctg 768 Val Pro Cys Asp Lys Pro Phe Ser Glu Glu Gln Ala Arg Leu Tyr Leu 245 250 255 cgg gac gtc atc ctg ggc ctc gag tac ttg cac tgc cag aag atc gtc 816 Arg Asp Val Ile Leu Gly Leu Glu Tyr Leu His Cys Gln Lys Ile Val 260 265 270 cac agg gac atc aag cca tcc aac ctg ctc ctg ggg gat gat ggg cac 864 His Arg Asp Ile Lys Pro Ser Asn Leu Leu Leu Gly Asp Asp Gly His 275 280 285 gtg aag atc gcc gac ttt ggc gtc agc aac cag ttt gag ggg aac gac 912 Val Lys Ile Ala Asp Phe Gly Val Ser Asn Gln Phe Glu Gly Asn Asp 290 295 300 gct cag ctg tcc agc acg gcg gga acc cca gca ttc atg gcc ccc gag 960 Ala Gln Leu Ser Ser Thr Ala Gly Thr Pro Ala Phe Met Ala Pro Glu 305 310 315 320 gcc att tct gat tcc ggc cag agc ttc agt ggg aag gcc ttg gat gta 1008 Ala Ile Ser Asp Ser Gly Gln Ser Phe Ser Gly Lys Ala Leu Asp Val 325 330 335 tgg gcc act ggc gtc acg ttg tac tgc ttt gtc tat ggg aag tgc ccg 1056 Trp Ala Thr Gly Val Thr Leu Tyr Cys Phe Val Tyr Gly Lys Cys Pro 340 345 350 ttc atc gac gat ttc atc ctg gcc ctc cac agg aag atc aag aat gag 1104 Phe Ile Asp Asp Phe Ile Leu Ala Leu His Arg Lys Ile Lys Asn Glu 355 360 365 ccc gtg gtg ttt cct gag ggg cca gaa atc agc gag gag ctc aag gac 1152 Pro Val Val Phe Pro Glu Gly Pro Glu Ile Ser Glu Glu Leu Lys Asp 370 375 380 ctg atc ctg aag atg tta gac aag aat ccc gag acg aga att ggg gtg 1200 Leu Ile Leu Lys Met Leu Asp Lys Asn Pro Glu Thr Arg Ile Gly Val 385 390 395 400 cca gac atc aag ttg cac cct tgg gtg acc aag aac ggg gag gag ccc 1248 Pro Asp Ile Lys Leu His Pro Trp Val Thr Lys Asn Gly Glu Glu Pro 405 410 415 ctt cct tcg gag gag gag cac tgc agc gtg gtg gag gtg aca gag gag 1296 Leu Pro Ser Glu Glu Glu His Cys Ser Val Val Glu Val Thr Glu Glu 420 425 430 gag gtt aag aac tca gtc agg ctc atc ccc agc tgg acc acg gtg atc 1344 Glu Val Lys Asn Ser Val Arg Leu Ile Pro Ser Trp Thr Thr Val Ile 435 440 445 ctg gtg aag tcc atg ctg agg aag cgt tcc ttt ggg aac ccg ttt gag 1392 Leu Val Lys Ser Met Leu Arg Lys Arg Ser Phe Gly Asn Pro Phe Glu 450 455 460 ccc caa gca cgg agg gaa gag cga tcc atg tct gct cca gga aac cta 1440 Pro Gln Ala Arg Arg Glu Glu Arg Ser Met Ser Ala Pro Gly Asn Leu 465 470 475 480 ctg gtg aaa gaa ggg ttt ggt gaa ggg ggc aag agc cca gag ctc ccc 1488 Leu Val Lys Glu Gly Phe Gly Glu Gly Gly Lys Ser Pro Glu Leu Pro 485 490 495 ggc gtc cag gct tac cac aac gga aga gac ctc ccg ctg ggg ccg ggc 1536 Gly Val Gln Ala Tyr His Asn Gly Arg Asp Leu Pro Leu Gly Pro Gly 500 505 510 agg cct ggc tca gct gcc aca ggc ata tgg tgg aga ggg ggg tac cct 1584 Arg Pro Gly Ser Ala Ala Thr Gly Ile Trp Trp Arg Gly Gly Tyr Pro 515 520 525 gcc cac ctt ggg gtg gtg gca cca gag ctc ttg tct att cag acg ctg 1632 Ala His Leu Gly Val Val Ala Pro Glu Leu Leu Ser Ile Gln Thr Leu 530 535 540 gta tgg ggg ctc gga ccc ctc act ggg gac agg gcc agt gtt gga gaa 1680 Val Trp Gly Leu Gly Pro Leu Thr Gly Asp Arg Ala Ser Val Gly Glu 545 550 555 560 ttc tga 1686 Phe * 44 178 PRT Artificial Sequence Consensus amino acid sequence 44 Glu Val Thr Leu Leu Asp Thr Lys Thr Ala Thr Gly Glu Leu Gly Trp 1 5 10 15 Leu Thr Tyr Pro Val Pro Ser Gly Trp Glu Glu Val Ser Gly Leu Asp 20 25 30 Glu Asn Asn Arg Pro Ile Arg Thr Tyr Gln Val Cys Asn Val Met Glu 35 40 45 Pro Asn Gln Asn Asn Trp Leu Arg Thr Asn Trp Ile Glu Arg Arg Gly 50 55 60 Ala Gln Arg Val Tyr Val Glu Leu Lys Phe Thr Val Arg Asp Cys Asn 65 70 75 80 Ser Leu Pro Gly Val Leu Gly Thr Cys Lys Glu Thr Phe Asn Leu Tyr 85 90 95 Tyr Tyr Glu Ser Asp Glu Asp Val Gly Thr Ala Leu Pro Ala Trp Arg 100 105 110 Glu Asn Gln Tyr Ile Lys Val Asp Thr Ile Ala Ala Asp Glu Ser Phe 115 120 125 Thr Gln Val Asp Leu Gly Asp Arg Val Leu Lys Leu Asn Thr Glu Val 130 135 140 Arg Ser Val Gly Pro Leu Ser Lys Lys Gly Phe Tyr Leu Ala Phe Gln 145 150 155 160 Asp Val Gly Ala Cys Ile Ala Leu Val Ser Val Arg Val Phe Tyr Lys 165 170 175 Lys Cys 45 273 PRT Artificial Sequence Consensus amino acid sequence 45 Tyr Glu Leu Leu Glu Lys Leu Gly Glu Gly Ser Phe Gly Lys Val Tyr 1 5 10 15 Lys Ala Lys His Lys Thr Gly Lys Ile Val Ala Val Lys Ile Leu Lys 20 25 30 Lys Glu Ser Leu Ser Leu Arg Glu Ile Gln Ile Leu Lys Arg Leu Ser 35 40 45 His Pro Asn Ile Val Arg Leu Leu Gly Val Phe Glu Asp Thr Asp Asp 50 55 60 His Leu Tyr Leu Val Met Glu Tyr Met Glu Gly Gly Asp Leu Phe Asp 65 70 75 80 Tyr Leu Arg Arg Asn Gly Pro Leu Ser Glu Lys Glu Ala Lys Lys Ile 85 90 95 Ala Leu Gln Ile Leu Arg Gly Leu Glu Tyr Leu His Ser Asn Gly Ile 100 105 110 Val His Arg Asp Leu Lys Pro Glu Asn Ile Leu Leu Asp Glu Asn Gly 115 120 125 Thr Val Lys Ile Ala Asp Phe Gly Leu Ala Arg Leu Leu Glu Lys Leu 130 135 140 Thr Thr Phe Val Gly Thr Pro Trp Tyr Met Met Ala Pro Glu Val Ile 145 150 155 160 Leu Glu Gly Arg Gly Tyr Ser Ser Lys Val Asp Val Trp Ser Leu Gly 165 170 175 Val Ile Leu Tyr Glu Leu Leu Thr Gly Gly Pro Leu Phe Pro Gly Ala 180 185 190 Asp Leu Pro Ala Phe Thr Gly Gly Asp Glu Val Asp Gln Leu Ile Ile 195 200 205 Phe Val Leu Lys Leu Pro Phe Ser Asp Glu Leu Pro Lys Thr Arg Ile 210 215 220 Asp Pro Leu Glu Glu Leu Phe Arg Ile Lys Lys Arg Arg Leu Pro Leu 225 230 235 240 Pro Ser Asn Cys Ser Glu Glu Leu Lys Asp Leu Leu Lys Lys Cys Leu 245 250 255 Asn Lys Asp Pro Ser Lys Arg Pro Gly Ser Ala Thr Ala Lys Glu Ile 260 265 270 Leu 46 180 PRT Artificial Sequence Consensus amino acid sequence 46 Glu Val Thr Leu Leu Asp Thr Lys Thr Val Gln Gly Glu Leu Gly Trp 1 5 10 15 Ile Thr Tyr Pro Pro Gln Asn Gly Gly Trp Glu Glu Val Ser Gly Met 20 25 30 Asp Glu Asn Asn Thr Pro Ile Arg Thr Tyr Gln Val Cys Asn Val Met 35 40 45 Glu Pro His Asn Gln Asn Asn Trp Leu Arg Thr Asn Trp Ile Pro Arg 50 55 60 Arg Gly Ala Gln Arg Ile Tyr Val Glu Leu Lys Phe Thr Val Arg Asp 65 70 75 80 Cys Asn Ser Leu Pro Gly Val Ala Gly Thr Cys Lys Glu Thr Phe Asn 85 90 95 Leu Tyr Tyr Tyr Glu Ser Asp Glu Asp Thr Gly Thr Ala Thr Ser Pro 100 105 110 Asn Trp Arg Glu Asn Gln Tyr Val Lys Ile Asp Thr Ile Ala Ala Asp 115 120 125 Glu Ser Phe Thr Gln Met Asp Leu Gly Asp Arg Val Met Lys Leu Asn 130 135 140 Thr Glu Val Arg Ser Ile Gly Pro Leu Ser Lys Lys Gly Phe Tyr Leu 145 150 155 160 Ala Phe Gln Asp Val Gly Ala Cys Ile Ala Leu Ile Ser Val Arg Val 165 170 175 Tyr Tyr Lys Lys 180 47 127 PRT Artificial Sequence Consensus amino acid sequence 47 Tyr Arg Ala Pro Ser Asp Pro Pro Ser Met Pro Cys Thr Arg Pro Pro 1 5 10 15 Ser Ala Pro Arg Asn Leu Ile Ser Asn Phe Val Asn Glu Thr Ser Val 20 25 30 Met Leu Glu Trp Ser Pro Pro Ala Asp Thr Gly Gly Arg Ser Asp Ile 35 40 45 Thr Tyr Asn Val Ile Cys Lys Lys Cys Arg Ser Trp Gly Asp Lys Gly 50 55 60 Lys Cys Asn Pro Cys Gly Asp Asn Val His Phe Ser Pro Arg Gln Thr 65 70 75 80 Gly Leu Thr Glu Thr Arg Val Thr Val Thr Asp Leu Glu Pro His Thr 85 90 95 Asn Tyr Thr Phe Glu Val Glu Ala Val Asn Gly Val Ser Asp Leu Ser 100 105 110 Pro Ser Pro Pro Gln Tyr Ala Ser Val Asn Val Thr Thr Asn Gln 115 120 125 48 50 PRT Artificial Sequence Consensus amino acid sequence 48 Glu Gly Val Val Thr Lys Arg Ser Phe Pro Ala Ile Gly Val Glu Ala 1 5 10 15 Phe Cys Pro Ser Phe Leu Arg Ala Gly Phe Leu Asn Gly Ile Gln Ala 20 25 30 Pro His Pro Val Pro Gly Gly Gly Ser Leu Pro Pro Arg Ile Pro Ala 35 40 45 Gly Arg 50 49 59 PRT Artificial Sequence Consensus amino acid sequence 49 Leu Gly Lys Cys Lys Cys Lys Ala Gly Tyr Glu Pro Asn Glu Asn Asn 1 5 10 15 Lys Thr Cys Gln Ala Cys Pro Pro Gly Thr Tyr Lys Ala Glu Ala Gly 20 25 30 Asp Ser Ser Cys Ser Pro Cys Pro Pro His Ser Thr Thr Thr Ser Glu 35 40 45 Gly Ser Thr Thr Cys Thr Cys Glu Cys Gly Tyr 50 55 50 178 PRT Artificial Sequence Consensus amino acid sequence 50 Met Val Gln Glu Tyr Val Arg Tyr Gly Pro Leu Asp Leu Phe Leu His 1 5 10 15 Lys Asn Lys Pro Asn Val Thr Leu His Trp Lys Leu Asp Val Ala Lys 20 25 30 Gln Leu Ala Arg Ala Met His Tyr Leu Glu Asp Lys Lys Leu Val His 35 40 45 Gly Asn Val Cys Cys Lys Asn Ile Leu Val Thr Arg Glu Gly Pro Glu 50 55 60 Lys Asn Ser Tyr Pro Pro Phe Ile Lys Leu Ser Asp Pro Gly Ile Pro 65 70 75 80 Ile Thr Val Leu Thr Arg Glu Tyr Arg Val Glu Arg Ile Pro Trp Ile 85 90 95 Pro Pro Glu Cys Ile Glu Asn Pro Gln Asn Leu Lys Thr Asp Gln Phe 100 105 110 Ala Asp Lys Trp Ser Phe Gly Thr Thr Leu Trp Glu Ile Cys Ser Asn 115 120 125 Gly Glu Glu Pro Leu Ser Thr Leu Arg Gln Glu Glu Leu Lys Glu Arg 130 135 140 Phe Tyr Glu Asp Arg His Gln Leu Pro Ala Pro Lys Trp Lys Glu Leu 145 150 155 160 Ala Asn Leu Ile Asn His Cys Met Asp Tyr Asp Pro Thr Gln Arg Pro 165 170 175 Phe Phe 51 55 PRT Artificial Sequence Consensus amino acid sequence 51 Arg Arg Lys Gly Tyr Ser Lys Ala Glu Gln Glu Tyr Asp Glu Lys Lys 1 5 10 15 Gln His Tyr His Asn Gly His Leu Lys Ala Pro Gly Val Lys Thr Tyr 20 25 30 Ile Asp Pro Phe Thr Tyr Glu Asp Pro Asn Gln Ala Val Arg Glu Phe 35 40 45 Ala Lys Glu Ile Asp Val Ser 50 55 52 278 PRT Artificial Sequence Consensus amino acid sequence 52 Tyr Glu Leu Leu Glu Lys Leu Gly Glu Gly Ser Phe Gly Lys Val Tyr 1 5 10 15 Lys Ala Lys His Lys Thr Gly Lys Ile Val Ala Val Lys Ile Leu Lys 20 25 30 Lys Glu Ser Leu Ser Leu Arg Glu Ile Gln Ile Leu Lys Arg Leu Ser 35 40 45 His Pro Asn Ile Val Arg Leu Leu Gly Val Phe Glu Asp Thr Asp Asp 50 55 60 His Leu Tyr Leu Val Met Glu Tyr Met Glu Gly Gly Asp Leu Phe Asp 65 70 75 80 Tyr Leu Arg Arg Asn Gly Pro Leu Ser Glu Lys Glu Ala Lys Lys Ile 85 90 95 Ala Leu Gln Ile Leu Arg Gly Leu Glu Tyr Leu His Ser Asn Gly Ile 100 105 110 Val His Arg Asp Leu Lys Pro Glu Asn Ile Leu Leu Asp Glu Asn Gly 115 120 125 Thr Val Lys Ile Ala Asp Phe Gly Leu Ala Arg Leu Leu Glu Lys Leu 130 135 140 Thr Thr Phe Val Gly Thr Pro Trp Tyr Met Met Ala Pro Glu Val Ile 145 150 155 160 Leu Glu Gly Arg Gly Tyr Ser Ser Lys Val Asp Val Trp Ser Leu Gly 165

170 175 Val Ile Leu Tyr Glu Leu Leu Thr Gly Gly Pro Leu Phe Pro Gly Ala 180 185 190 Asp Leu Pro Ala Phe Thr Gly Gly Asp Glu Val Asp Gln Leu Ile Ile 195 200 205 Phe Val Leu Lys Leu Pro Phe Ser Asp Glu Leu Pro Lys Thr Arg Ile 210 215 220 Asp Pro Leu Glu Glu Leu Phe Arg Ile Lys Lys Arg Arg Leu Pro Leu 225 230 235 240 Pro Ser Asn Cys Ser Glu Glu Leu Lys Asp Leu Leu Lys Lys Cys Leu 245 250 255 Asn Lys Asp Pro Ser Lys Arg Pro Gly Ser Ala Thr Ala Lys Glu Ile 260 265 270 Leu Asn His Pro Trp Phe 275 53 48 PRT Artificial Sequence Consensus amino acid sequence 53 Gly Thr Arg Trp Tyr Met Ala Pro Glu Val Leu Met Gly Ser Ser Tyr 1 5 10 15 Gly Gln Tyr Ser Glu Lys Ser Asp Val Trp Ser Phe Gly Val Ile Leu 20 25 30 Tyr Glu Leu Leu Thr Gly Lys Pro Pro Phe Phe Pro Gly Ser Ser Glu 35 40 45 54 100 PRT Artificial Sequence Consensus amino acid sequence 54 Glu Met Met Glu Lys Leu Gln Lys Gln Ser Met Ser Glu Lys Lys Met 1 5 10 15 Glu Glu Met Ser Trp Val Ser Gln Leu Met Lys Ile Ala Tyr Gln Ile 20 25 30 Ala Lys Gly Leu Glu Tyr Leu His Ser Lys Ser Asn Lys Gln Asn Ile 35 40 45 Ile His Arg Asp Leu Lys Pro Glu Asn Ile Leu Leu Asp Asn Asn Met 50 55 60 Val Ala Lys Gly Asp Ser Glu Ile Lys Val Val Lys Ile Ala Asp Phe 65 70 75 80 Gly Leu Ala Arg Met Ile Glu Glu Ser Ser Glu Glu Ser Ser Ser Ser 85 90 95 Ser Ser Ser Thr 100 55 134 PRT Artificial Sequence Consensus amino acid sequence 55 Lys Ala Ala Thr Lys Val Ala Val Lys Lys Lys Met Lys Glu Glu Glu 1 5 10 15 Lys Lys Glu Ser Lys Thr Ser Met Arg Glu Glu Glu Met Gln Met Met 20 25 30 Met Glu Ile Glu Thr His Pro Asn Ile Met Ile Ile Arg His Val Asn 35 40 45 Leu Val Val Val Met Gly Tyr Cys Thr Tyr Glu Glu Ser Glu Glu Glu 50 55 60 Asp Glu Asn Lys Leu Tyr Ile Val Met Glu Tyr Met Asn Gly Gly Ser 65 70 75 80 Leu Glu Asp Tyr Leu Glu Met Met Glu Lys Leu Gln Lys Gln Ser Met 85 90 95 Ser Glu Lys Lys Met Glu Glu Met Ser Trp Val Ser Gln Leu Met Lys 100 105 110 Ile Ala Tyr Gln Ile Ala Lys Gly Leu Glu Tyr Leu His Ser Lys Ser 115 120 125 Asn Lys Gln Asn Ile Ile 130 56 40 PRT Artificial Sequence Consensus amino acid sequence 56 Glu Glu Leu Ser Ala His Glu Ile Lys Gln His Pro Trp Phe Arg Lys 1 5 10 15 Arg Asp Ser Phe Ser Asp Met His Ser Val Gly Tyr Met Met Tyr Glu 20 25 30 Met Met Ser Gly Gln Pro Pro Phe 35 40 57 80 PRT Artificial Sequence Consensus amino acid sequence 57 Tyr Glu Leu Leu Lys Lys Leu Gly Glu Gly Ser Phe Gly Lys Val Tyr 1 5 10 15 Lys Ala Arg His Lys Val Val Tyr Lys Ala Lys Asp Lys Ser Lys Glu 20 25 30 Thr Tyr Ala Ala Lys Val Val Ala Lys Leu Lys Val Leu Lys Ala Ala 35 40 45 Thr Lys Val Ala Val Lys Lys Lys Met Lys Glu Glu Glu Lys Lys Glu 50 55 60 Ser Lys Thr Ser Met Arg Glu Glu Glu Met Gln Met Met Met Glu Ile 65 70 75 80 58 27 PRT Artificial Sequence Consensus amino acid sequence 58 Ser Glu Ala Val Lys Asp Leu Ile Lys Lys Cys Trp Gln Lys Asp Pro 1 5 10 15 Glu Lys Arg Pro Thr Phe Ala Gln Val Val Glu 20 25 59 162 PRT Artificial Sequence Consensus amino acid sequence 59 Ser Leu Gly Val Cys Ile Phe Val Met Ala Thr Gly Ser Cys Pro Phe 1 5 10 15 Ile Leu Glu Ser Arg Asn Thr Met Met Glu Ser Ile Gln Ala Gly Ile 20 25 30 Leu Gly Ser Pro Val Leu Ala Ser Asp Lys Ile Gln Ser Leu Val Glu 35 40 45 Gln Leu Ile His Val Asn Pro Ser Glu Arg Met Ser Leu Lys Ser Leu 50 55 60 Ile Glu Asp Asp Trp Met Thr Ser Asp Leu Val Trp Asn Tyr Phe Ile 65 70 75 80 Ser Cys His Glu Asp Leu Ile Arg Glu Leu Pro Val Val Asp Arg Phe 85 90 95 Ile Pro Ala Glu Ser Leu Glu Lys Ser Thr Val Gln Arg Asp Gly Ser 100 105 110 Glu Ile Ser Ile Glu Thr Leu Asp Glu Gly Tyr Lys Ser Val Ala Ser 115 120 125 Asp His Pro Glu Glu Pro Ala Val Ser Gly Glu Gln Gln Val Leu Thr 130 135 140 Glu Pro Val Pro Lys Lys Tyr His Lys Lys Phe Ala Val Phe Ala Met 145 150 155 160 Glu Asn 60 141 PRT Artificial Sequence Consensus amino acid sequence 60 Ile Ala Ser Gly Arg Phe Gly Thr Val Phe Leu Gly Thr Ile Thr Asp 1 5 10 15 Ser Met Leu Gln Val Ala Ile Lys Glu Tyr His Glu Thr Phe His Asp 20 25 30 Ala Val Leu Thr Ala His Asp Glu Gly Ser Thr Leu Gln Lys Ile Ile 35 40 45 Ser Ile Glu His Pro Ala Ile Val Gln Thr Phe Ser Val Ser His Phe 50 55 60 Gln Asp Ile Val Tyr Lys Val Met Glu Phe His Ser Trp Thr Leu His 65 70 75 80 Glu Lys Arg Val Tyr Phe Glu Lys Ile Asp Arg Thr Asn Asn Asp Ile 85 90 95 Leu Asp Lys Gly Lys Tyr Asp Glu Ser Gln Thr Lys Leu Val Leu Val 100 105 110 Gln Ala Thr Arg Ala Leu Glu Tyr Leu His Ala Gln Asn Leu Cys His 115 120 125 Gly Thr Leu His Thr Lys Asn Ile Phe Leu Gln Glu Asn 130 135 140 61 278 PRT Artificial Sequence Consensus amino acid sequence 61 Tyr Glu Leu Leu Glu Lys Leu Gly Glu Gly Ser Phe Gly Lys Val Tyr 1 5 10 15 Lys Ala Lys His Lys Thr Gly Lys Ile Val Ala Val Lys Ile Leu Lys 20 25 30 Lys Glu Ser Leu Ser Leu Arg Glu Ile Gln Ile Leu Lys Arg Leu Ser 35 40 45 His Pro Asn Ile Val Arg Leu Leu Gly Val Phe Glu Asp Thr Asp Asp 50 55 60 His Leu Tyr Leu Val Met Glu Tyr Met Glu Gly Gly Asp Leu Phe Asp 65 70 75 80 Tyr Leu Arg Arg Asn Gly Pro Leu Ser Glu Lys Glu Ala Lys Lys Ile 85 90 95 Ala Leu Gln Ile Leu Arg Gly Leu Glu Tyr Leu His Ser Asn Gly Ile 100 105 110 Val His Arg Asp Leu Lys Pro Glu Asn Ile Leu Leu Asp Glu Asn Gly 115 120 125 Thr Val Lys Ile Ala Asp Phe Gly Leu Ala Arg Leu Leu Glu Lys Leu 130 135 140 Thr Thr Phe Val Gly Thr Pro Trp Tyr Met Met Ala Pro Glu Val Ile 145 150 155 160 Leu Glu Gly Arg Gly Tyr Ser Ser Lys Val Asp Val Trp Ser Leu Gly 165 170 175 Val Ile Leu Tyr Glu Leu Leu Thr Gly Gly Pro Leu Phe Pro Gly Ala 180 185 190 Asp Leu Pro Ala Phe Thr Gly Gly Asp Glu Val Asp Gln Leu Ile Ile 195 200 205 Phe Val Leu Lys Leu Pro Phe Ser Asp Glu Leu Pro Lys Thr Arg Ile 210 215 220 Asp Pro Leu Glu Glu Leu Phe Arg Ile Lys Lys Arg Arg Leu Pro Leu 225 230 235 240 Pro Ser Asn Cys Ser Glu Glu Leu Lys Asp Leu Leu Lys Lys Cys Leu 245 250 255 Asn Lys Asp Pro Ser Lys Arg Pro Gly Ser Ala Thr Ala Lys Glu Ile 260 265 270 Leu Asn His Pro Trp Phe 275 62 80 PRT Artificial Sequence Consensus amino acid sequence 62 Met Glu Arg Ser Pro Ala Val Cys Cys Gln Asp Pro Arg Ala Glu Leu 1 5 10 15 Val Glu Arg Val Ala Ala Ile Ser Val Ala His Leu Glu Glu Ala Glu 20 25 30 Glu Gly Pro Glu Pro Ala Ser Asn Gly Val Asp Pro Pro Pro Arg Ala 35 40 45 Arg Ala Ala Ser Val Ile Pro Gly Ser Ala Ser Arg Pro Thr Pro Val 50 55 60 Arg Pro Ser Leu Ser Ala Arg Lys Phe Ser Leu Gln Glu Arg Pro Ala 65 70 75 80 63 61 PRT Artificial Sequence Consensus amino acid sequence 63 Leu Lys Thr His Lys Trp Val Thr Arg His Gly Glu Glu Pro Leu Pro 1 5 10 15 Ser Glu Glu Glu Asn Cys Thr Leu Val Glu Val Thr Glu Glu Glu Val 20 25 30 Glu Asn Ser Val Lys His Ile Pro Ser Leu Thr Thr Val Ile Leu Val 35 40 45 Lys Thr Met Leu Arg Lys Arg Ser Phe Gly Asn Pro Phe 50 55 60 64 47 PRT Artificial Sequence Consensus amino acid sequence VARIANT (1)...(47) Xaa = Any Amino Acid 64 Gly Xaa Cys Leu Gly Ala Gln Val Gly Pro Tyr Ser Thr Gly Pro Ala 1 5 10 15 Ser His Met Cys Pro Arg Ser Trp Arg Arg Pro Thr Ile Glu Ser His 20 25 30 Arg Val Ala Ile Ser Asp Thr Glu Asp Cys Val Gln Leu Asn Gln 35 40 45 65 36 PRT Artificial Sequence Consensus amino acid sequence 65 Glu Pro Gln Ala Arg Arg Glu Glu Arg Ser Met Ser Ala Pro Gly Asn 1 5 10 15 Leu Leu Leu Lys Glu Gly Cys Gly Glu Gly Gly Lys Ser Pro Glu Leu 20 25 30 Pro Gly Val Gln 35 66 17 PRT Artificial Sequence Consensus amino acid sequence VARIANT (1)...(1) Xaa at position 1 can be L, I or V VARIANT (3)...(3) Xaa at position 3 can be any amino acid except P VARIANT (5)...(5) Xaa at position 5 can be any amino acid except P VARIANT (6)...(6) Xaa at position 6 can be F, Y, W, M, G, S, T, N or H VARIANT (7)...(7) Xaa at position 7 can be S, G or A VARIANT (8)...(8) Xaa at position 8 can be any amino acid except P or W VARIANT (9)...(9) Xaa at position 9 can be L, I, V, C, A or T VARIANT (10)...(10) Xaa at position 10 can be any amino acid except P or D VARIANT (11)...(11) Xaa = Any Amino Acid VARIANT (12)...(12) Xaa at position 12 can be G, S, T, A, C, L, I, V, M, F or Y VARIANT (13)...(13) Xaa at position 13 can be 5 to 18 of any amino acid VARIANT (14)...(14) Xaa at position 14 can be L, I, V, M, F, Y, W, C, S, T, A or R VARIANT (15)...(15) Xaa at position 15 can be A, I, V or P VARIANT (16)...(16) Xaa at position 9 can be L, I, V, M, F, A, G, C, K or R 66 Xaa Gly Xaa Gly Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 1 5 10 15 Lys 67 13 PRT Artificial Sequence Consensus amino acid sequence VARIANT (1)...(1) Xaa at position 1 can be L, I, V, M, F, Y or C VARIANT (2)...(2) Xaa = Any Amino Acid VARIANT (3)...(3) Xaa at position 3 can be H or Y VARIANT (4)...(4) Xaa = Any Amino Acid VARIANT (6)...(6) Xaa at position 6 can be L, I, V, M, F or Y VARIANT (7)...(7) Xaa at position 7 can be R, S, T, A or C VARIANT (8)...(9) Xaa = Any Amino Acid VARIANT (11)...(13) Xaa at positions 11 to 13 can be L, I, V, M, F, Y or C 67 Xaa Xaa Xaa Xaa Asp Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa 1 5 10 68 13 PRT Artificial Sequence Consensus amino acid sequence VARIANT (1)...(1) Xaa at position 1 can be L, I, V, M, F, Y or C VARIANT (2)...(2) Xaa = Any Amino Acid VARIANT (3)...(3) Xaa at position 3 can be H or Y, VARIANT (4)...(4) Xaa = Any Amino Acid VARIANT (6)...(6) Xaa at position 6 can be L, I, V, M, F or Y VARIANT (80)...(9) Xaa = Any Amino Acid VARIANT (11)...(13) Xaa at positions 11 to 13 can be L, I, V, M, F, Y, C or T 68 Xaa Xaa Xaa Xaa Asp Xaa Lys Xaa Xaa Asn Xaa Xaa Xaa 1 5 10 69 21 PRT Artificial Sequence Consensus amino acid sequence VARIANT (2)...(2) Xaa = Any Amino Acid VARIANT (3)...(3) Xaa at position 3 can be D or N VARIANT (4)...(4) Xaa = Any Amino Acid VARIANT (5)...(5) Xaa at position 5 can be G, A or W VARIANT (6)...(6) Xaa at position 6 can be G or A VARIANT (8)...(8) Xaa at position 8 can be L, I, V or M VARIANT (9)...(9) Xaa at position 9 can be S or A VARIANT (10)...(11) Xaa at positions 10 to 11 can be L, I, V or M VARIANT (12)...(12) Xaa at position 12 can be S or A VARIANT (13)...(13) Xaa at position 13 can be L or V VARIANT (14)...(14) Xaa at position 14 can be K, R, H or Q VARIANT (15)...(15) Xaa at position 15 can be L, I, V or A VARIANT (16)...(18) Xaa = Any Amino Acid VARIANT (19)...(19) Xaa at position 19 can be K or R VARIANT (21)...(21) Xaa at position 21 can be P, S, A or W 69 Phe Xaa Xaa Xaa Xaa Xaa Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 1 5 10 15 Xaa Xaa Xaa Cys Xaa 20 70 20 PRT Artificial Sequence Consensus amino acid sequence VARIANT (2)...(3) Xaa = Any Amino Acid VARIANT (4)...(4) Xaa at position 4 can be D or E VARIANT (6)...(6) Xaa at position 6 can be D, E or Q VARIANT (8)...(8) Xaa at position 8 can be 2 to 3 residues of any amino acid VARIANT (9)...(9) Xaa at position 9 can be P, A or Q VARIANT (10)...(10) Xaa at position 10 can be L, I, V, M or T VARIANT (11)...(11) Xaa at position 11 can be G or T VARIANT (12)...(12) Xaa = Any Amino Acid VARIANT (14)...(14) Xaa = Any Amino Acid VARIANT (16)...(17) Xaa = Any Amino Acid VARIANT (19)...(19) Xaa at position 19 can be H, F or Y VARIANT (20)...(20) Xaa at position 20 can be E or Q 70 Cys Xaa Xaa Xaa Gly Xaa Trp Xaa Xaa Xaa Xaa Xaa Cys Xaa Cys Xaa 1 5 10 15 Xaa Gly Xaa Xaa 20 71 9 PRT Artificial Sequence Consensus amino acid sequence VARIANT (2)...(2) Xaa = Any Amino Acid VARIANT (4)...(5) Xaa = Any Amino Acid VARIANT (6)...(6) Xaa at position 6 can be G or P VARIANT (7)...(7) Xaa at position 7 can be F, Y or W VARIANT (8)...(8) Xaa at position 8 can be 4 to 8 residues of any amino acid 71 Cys Xaa Cys Xaa Xaa Xaa Xaa Xaa Cys 1 5 72 8 PRT Artificial Sequence Consensus amino acid sequence VARIANT (1)...(1) Xaa at position 1 can be A or G VARIANT (2)...(5) Xaa = Any Amino Acid VARIANT (8)...(8) Xaa at position 8 can be S or T 72 Xaa Xaa Xaa Xaa Xaa Gly Lys Xaa 1 5 73 1154 DNA Homo sapiens CDS (22)...(870) 73 cggacgcgtg ggtccgtgac c atg aag gtc aag gtc atc ccc gtg ctc gag 51 Met Lys Val Lys Val Ile Pro Val Leu Glu 1 5 10 gac aac tac atg tac ctg gtc atc gag gag ctc acg cgc gag gcg gtg 99 Asp Asn Tyr Met Tyr Leu Val Ile Glu Glu Leu Thr Arg Glu Ala Val 15 20 25 gcc gtg gac gtg gct gtg ccc aag agg ctg ctg gag atc gtg ggc cgg 147 Ala Val Asp Val Ala Val Pro Lys Arg Leu Leu Glu Ile Val Gly Arg 30 35 40 gag ggg gtg tct ctg acc gct gtg ctg acc acc cac cat cac tgg gac 195 Glu Gly Val Ser Leu Thr Ala Val Leu Thr Thr His His His Trp Asp 45 50 55 cac gcg cgg gga aac ccg gag ctg gcg cgg ctt cgt ccc ggg ctg gcg 243 His Ala Arg Gly Asn Pro Glu Leu Ala Arg Leu Arg Pro Gly Leu Ala 60 65 70 gtg ctg ggc gcg gac gag cgc atc ttc tcg ctg acg cgc agg ctg gcg 291 Val Leu Gly Ala Asp Glu Arg Ile Phe Ser Leu Thr Arg Arg Leu Ala 75 80 85 90 cac ggc gag gag ctg cgg ttc ggg gcc atc cac gtg cgt tgc ctc ctg 339 His Gly Glu Glu Leu Arg Phe Gly Ala Ile His Val Arg Cys Leu Leu 95 100 105 acg ccc ggc cac acc gcc ggc cac atg agc tac ttc ctg tgg gag gac 387 Thr Pro Gly His Thr Ala Gly His Met Ser Tyr Phe Leu Trp Glu Asp 110 115 120 gat tgc ccg gac cca ccc gcc ctg ttc tcg ggc gac gcg ctg tcg gtg 435 Asp Cys Pro Asp Pro Pro Ala Leu Phe Ser Gly Asp Ala Leu Ser Val 125 130 135 gcc ggc tgc ggc tcg tgc ctg gag ggc agc gcc cag cag atg tac cag 483 Ala Gly Cys Gly Ser Cys Leu Glu Gly Ser Ala Gln Gln Met Tyr Gln 140 145 150 agc ctg gcc gag ctg ggt acc ctg ccc ccc gag acg aag gtg ttc tgc 531 Ser Leu Ala Glu Leu Gly Thr Leu Pro Pro Glu Thr Lys Val Phe Cys 155 160 165 170 ggc cac gag cac acg ctt agc aac ctg gag ttt gcc cag aaa gtg gag 579 Gly His Glu His Thr Leu Ser Asn Leu Glu Phe Ala Gln Lys Val Glu 175 180 185 ccc tgc aac gac cac gtg aga gcc aag ctg tcc tgg gct aag aag agg 627 Pro Cys Asn Asp His Val Arg Ala Lys Leu Ser Trp Ala Lys Lys Arg

190 195 200 gat gag gat gac gtg ccc act gtg ccg tcg act ctg ggc gag gag cgc 675 Asp Glu Asp Asp Val Pro Thr Val Pro Ser Thr Leu Gly Glu Glu Arg 205 210 215 ctc tac aac ccc ttc ctg cgg gtg gca gag gag ccg gtg cgc aag ttc 723 Leu Tyr Asn Pro Phe Leu Arg Val Ala Glu Glu Pro Val Arg Lys Phe 220 225 230 acg ggc aag gcg gtc ccc gcc gac gtc ctg gag gcg cta tgc aag gag 771 Thr Gly Lys Ala Val Pro Ala Asp Val Leu Glu Ala Leu Cys Lys Glu 235 240 245 250 cgg gcg cgc ttc gaa cag gcg ggc gag ccg cgg cag cca cag gcg cgg 819 Arg Ala Arg Phe Glu Gln Ala Gly Glu Pro Arg Gln Pro Gln Ala Arg 255 260 265 gcc ctc ctt gcg ctg cag tgg ggg ctc ctg agt gca gcc cca cac gac 867 Ala Leu Leu Ala Leu Gln Trp Gly Leu Leu Ser Ala Ala Pro His Asp 270 275 280 tga gccacccaga ccctcacagg gctggggcct gcgtccctcc tcgtgacctc 920 * ggccagctgg acccacatga gggccacctc tggaaccttc ttcgaggccc tggccagcca 980 tctgcccagc ctcggagggt gggcaacctg gtgcttcccg ggtggacaca caggaccact 1040 cagtggggcc tgtgtgggcg ccgagacctg ggtgtctggg aagtggggca cacggggcct 1100 ccgaactatg aataaagctt tgaaagccgt tgtcaaaaaa aaaaaaaaaa aaaa 1154 74 282 PRT Homo sapiens 74 Met Lys Val Lys Val Ile Pro Val Leu Glu Asp Asn Tyr Met Tyr Leu 1 5 10 15 Val Ile Glu Glu Leu Thr Arg Glu Ala Val Ala Val Asp Val Ala Val 20 25 30 Pro Lys Arg Leu Leu Glu Ile Val Gly Arg Glu Gly Val Ser Leu Thr 35 40 45 Ala Val Leu Thr Thr His His His Trp Asp His Ala Arg Gly Asn Pro 50 55 60 Glu Leu Ala Arg Leu Arg Pro Gly Leu Ala Val Leu Gly Ala Asp Glu 65 70 75 80 Arg Ile Phe Ser Leu Thr Arg Arg Leu Ala His Gly Glu Glu Leu Arg 85 90 95 Phe Gly Ala Ile His Val Arg Cys Leu Leu Thr Pro Gly His Thr Ala 100 105 110 Gly His Met Ser Tyr Phe Leu Trp Glu Asp Asp Cys Pro Asp Pro Pro 115 120 125 Ala Leu Phe Ser Gly Asp Ala Leu Ser Val Ala Gly Cys Gly Ser Cys 130 135 140 Leu Glu Gly Ser Ala Gln Gln Met Tyr Gln Ser Leu Ala Glu Leu Gly 145 150 155 160 Thr Leu Pro Pro Glu Thr Lys Val Phe Cys Gly His Glu His Thr Leu 165 170 175 Ser Asn Leu Glu Phe Ala Gln Lys Val Glu Pro Cys Asn Asp His Val 180 185 190 Arg Ala Lys Leu Ser Trp Ala Lys Lys Arg Asp Glu Asp Asp Val Pro 195 200 205 Thr Val Pro Ser Thr Leu Gly Glu Glu Arg Leu Tyr Asn Pro Phe Leu 210 215 220 Arg Val Ala Glu Glu Pro Val Arg Lys Phe Thr Gly Lys Ala Val Pro 225 230 235 240 Ala Asp Val Leu Glu Ala Leu Cys Lys Glu Arg Ala Arg Phe Glu Gln 245 250 255 Ala Gly Glu Pro Arg Gln Pro Gln Ala Arg Ala Leu Leu Ala Leu Gln 260 265 270 Trp Gly Leu Leu Ser Ala Ala Pro His Asp 275 280 75 849 DNA Homo sapiens CDS (1)...(849) 75 atg aag gtc aag gtc atc ccc gtg ctc gag gac aac tac atg tac ctg 48 Met Lys Val Lys Val Ile Pro Val Leu Glu Asp Asn Tyr Met Tyr Leu 1 5 10 15 gtc atc gag gag ctc acg cgc gag gcg gtg gcc gtg gac gtg gct gtg 96 Val Ile Glu Glu Leu Thr Arg Glu Ala Val Ala Val Asp Val Ala Val 20 25 30 ccc aag agg ctg ctg gag atc gtg ggc cgg gag ggg gtg tct ctg acc 144 Pro Lys Arg Leu Leu Glu Ile Val Gly Arg Glu Gly Val Ser Leu Thr 35 40 45 gct gtg ctg acc acc cac cat cac tgg gac cac gcg cgg gga aac ccg 192 Ala Val Leu Thr Thr His His His Trp Asp His Ala Arg Gly Asn Pro 50 55 60 gag ctg gcg cgg ctt cgt ccc ggg ctg gcg gtg ctg ggc gcg gac gag 240 Glu Leu Ala Arg Leu Arg Pro Gly Leu Ala Val Leu Gly Ala Asp Glu 65 70 75 80 cgc atc ttc tcg ctg acg cgc agg ctg gcg cac ggc gag gag ctg cgg 288 Arg Ile Phe Ser Leu Thr Arg Arg Leu Ala His Gly Glu Glu Leu Arg 85 90 95 ttc ggg gcc atc cac gtg cgt tgc ctc ctg acg ccc ggc cac acc gcc 336 Phe Gly Ala Ile His Val Arg Cys Leu Leu Thr Pro Gly His Thr Ala 100 105 110 ggc cac atg agc tac ttc ctg tgg gag gac gat tgc ccg gac cca ccc 384 Gly His Met Ser Tyr Phe Leu Trp Glu Asp Asp Cys Pro Asp Pro Pro 115 120 125 gcc ctg ttc tcg ggc gac gcg ctg tcg gtg gcc ggc tgc ggc tcg tgc 432 Ala Leu Phe Ser Gly Asp Ala Leu Ser Val Ala Gly Cys Gly Ser Cys 130 135 140 ctg gag ggc agc gcc cag cag atg tac cag agc ctg gcc gag ctg ggt 480 Leu Glu Gly Ser Ala Gln Gln Met Tyr Gln Ser Leu Ala Glu Leu Gly 145 150 155 160 acc ctg ccc ccc gag acg aag gtg ttc tgc ggc cac gag cac acg ctt 528 Thr Leu Pro Pro Glu Thr Lys Val Phe Cys Gly His Glu His Thr Leu 165 170 175 agc aac ctg gag ttt gcc cag aaa gtg gag ccc tgc aac gac cac gtg 576 Ser Asn Leu Glu Phe Ala Gln Lys Val Glu Pro Cys Asn Asp His Val 180 185 190 aga gcc aag ctg tcc tgg gct aag aag agg gat gag gat gac gtg ccc 624 Arg Ala Lys Leu Ser Trp Ala Lys Lys Arg Asp Glu Asp Asp Val Pro 195 200 205 act gtg ccg tcg act ctg ggc gag gag cgc ctc tac aac ccc ttc ctg 672 Thr Val Pro Ser Thr Leu Gly Glu Glu Arg Leu Tyr Asn Pro Phe Leu 210 215 220 cgg gtg gca gag gag ccg gtg cgc aag ttc acg ggc aag gcg gtc ccc 720 Arg Val Ala Glu Glu Pro Val Arg Lys Phe Thr Gly Lys Ala Val Pro 225 230 235 240 gcc gac gtc ctg gag gcg cta tgc aag gag cgg gcg cgc ttc gaa cag 768 Ala Asp Val Leu Glu Ala Leu Cys Lys Glu Arg Ala Arg Phe Glu Gln 245 250 255 gcg ggc gag ccg cgg cag cca cag gcg cgg gcc ctc ctt gcg ctg cag 816 Ala Gly Glu Pro Arg Gln Pro Gln Ala Arg Ala Leu Leu Ala Leu Gln 260 265 270 tgg ggg ctc ctg agt gca gcc cca cac gac tga 849 Trp Gly Leu Leu Ser Ala Ala Pro His Asp * 275 280 76 2853 DNA Homo sapiens CDS (1)...(2853) 76 atg ctt ctg ctg ggc atc cta acc ctg gct ttc gcc ggg cga acc gct 48 Met Leu Leu Leu Gly Ile Leu Thr Leu Ala Phe Ala Gly Arg Thr Ala 1 5 10 15 gga ggc tct gag cca gag cgg gag gta gtc gtt ccc atc cga ctg gac 96 Gly Gly Ser Glu Pro Glu Arg Glu Val Val Val Pro Ile Arg Leu Asp 20 25 30 ccg gac att aac ggc cgc cgc tac tac tgg cgg ggt ccc gag gac tcc 144 Pro Asp Ile Asn Gly Arg Arg Tyr Tyr Trp Arg Gly Pro Glu Asp Ser 35 40 45 ggg gat cag gga ctc att ttt cag atc aca gca ttt cag gag gac ttt 192 Gly Asp Gln Gly Leu Ile Phe Gln Ile Thr Ala Phe Gln Glu Asp Phe 50 55 60 tac cta cac ctg acg ccg gat gct cag ttc ttg gct ccc gcc ttc tcc 240 Tyr Leu His Leu Thr Pro Asp Ala Gln Phe Leu Ala Pro Ala Phe Ser 65 70 75 80 act gag cat ctg ggc gtc ccc ctc cag ggg ctc acc ggg ggc tct tca 288 Thr Glu His Leu Gly Val Pro Leu Gln Gly Leu Thr Gly Gly Ser Ser 85 90 95 gac ctg cga cgc tgc ttc tat tct ggg gac gtg aac gcc gag ccg gac 336 Asp Leu Arg Arg Cys Phe Tyr Ser Gly Asp Val Asn Ala Glu Pro Asp 100 105 110 tcg ttc gct gct gtg agc ctg tgc ggg ggg ctc cgc gga gcc ttt ggc 384 Ser Phe Ala Ala Val Ser Leu Cys Gly Gly Leu Arg Gly Ala Phe Gly 115 120 125 tac cga ggc gcc gag tat gtc att agc ccg ctg ccc aat gct agc gcg 432 Tyr Arg Gly Ala Glu Tyr Val Ile Ser Pro Leu Pro Asn Ala Ser Ala 130 135 140 ccg gcg gcg cag cgc aac agc cag ggc gca cac ctt ctc cag cgc cgg 480 Pro Ala Ala Gln Arg Asn Ser Gln Gly Ala His Leu Leu Gln Arg Arg 145 150 155 160 ggt gtt ccg ggc ggg cct tcc gga gac ccc acc tct cgc tgc ggg gtg 528 Gly Val Pro Gly Gly Pro Ser Gly Asp Pro Thr Ser Arg Cys Gly Val 165 170 175 gcc tcg ggc tgg aac ccc gcc atc cta cgg gcc ctg gac cct tac aag 576 Ala Ser Gly Trp Asn Pro Ala Ile Leu Arg Ala Leu Asp Pro Tyr Lys 180 185 190 ccg cgg cgg gcg ggc ttc ggg gag agt cgt agc cgg cgc agg tct ggg 624 Pro Arg Arg Ala Gly Phe Gly Glu Ser Arg Ser Arg Arg Arg Ser Gly 195 200 205 cgc gcc aag cgt ttc gtg tct atc ccg cgg tac gtg gag acg ctg gtg 672 Arg Ala Lys Arg Phe Val Ser Ile Pro Arg Tyr Val Glu Thr Leu Val 210 215 220 gtc gcg gac gag tca atg gtc aag ttc cac ggc gcg gac ctg gaa cat 720 Val Ala Asp Glu Ser Met Val Lys Phe His Gly Ala Asp Leu Glu His 225 230 235 240 tat ctg ctg acg ctg ctg gca acg gcg gcg cga ctc tac cgc cat ccc 768 Tyr Leu Leu Thr Leu Leu Ala Thr Ala Ala Arg Leu Tyr Arg His Pro 245 250 255 agc atc ctc aac ccc atc aac atc gtt gtg gtc aag gtg ctg ctt ctt 816 Ser Ile Leu Asn Pro Ile Asn Ile Val Val Val Lys Val Leu Leu Leu 260 265 270 aga gat cgt gac tcc ggg ccc aag gtc acc ggc aat gcg gcc ctg acg 864 Arg Asp Arg Asp Ser Gly Pro Lys Val Thr Gly Asn Ala Ala Leu Thr 275 280 285 ctg cgc aac ttc tgt gcc tgg cag aag aag ctg aac aaa gtg agt gac 912 Leu Arg Asn Phe Cys Ala Trp Gln Lys Lys Leu Asn Lys Val Ser Asp 290 295 300 aag cac ccc gag tac tgg gac act gcc atc ctc ttc acc agg cag gac 960 Lys His Pro Glu Tyr Trp Asp Thr Ala Ile Leu Phe Thr Arg Gln Asp 305 310 315 320 ctg tgt gga gcc acc acc tgt gac acc ctg ggc atg gct gat gtg ggt 1008 Leu Cys Gly Ala Thr Thr Cys Asp Thr Leu Gly Met Ala Asp Val Gly 325 330 335 acc atg tgt gac ccc aag aga agc tgc tct gtc att gag gac gat ggg 1056 Thr Met Cys Asp Pro Lys Arg Ser Cys Ser Val Ile Glu Asp Asp Gly 340 345 350 ctt cca tca gcc ttc acc act gcc cac gag ctg ggc cac gtg ttc aac 1104 Leu Pro Ser Ala Phe Thr Thr Ala His Glu Leu Gly His Val Phe Asn 355 360 365 atg ccc cat gac aat gtg aaa gtc tgt gag gag gtg ttt ggg aag ctc 1152 Met Pro His Asp Asn Val Lys Val Cys Glu Glu Val Phe Gly Lys Leu 370 375 380 cga gcc aac cac atg atg tcc ccg acc ctc atc cag atc gac cgt gcc 1200 Arg Ala Asn His Met Met Ser Pro Thr Leu Ile Gln Ile Asp Arg Ala 385 390 395 400 aac ccc tgg tca gcc tgc agt gct gcc atc atc acc gac ttc ctg gac 1248 Asn Pro Trp Ser Ala Cys Ser Ala Ala Ile Ile Thr Asp Phe Leu Asp 405 410 415 agc ggg cac ggt gac tgc ctc ctg gac caa ccc agc aag ccc atc tcc 1296 Ser Gly His Gly Asp Cys Leu Leu Asp Gln Pro Ser Lys Pro Ile Ser 420 425 430 ctg ccc gag gat ctg ccg ggc gcc agc tac acc ctg agc cag cag tgc 1344 Leu Pro Glu Asp Leu Pro Gly Ala Ser Tyr Thr Leu Ser Gln Gln Cys 435 440 445 gag ctg gct ttt ggc gtg ggc tcc aag ccc tgt cct tac atg cag tac 1392 Glu Leu Ala Phe Gly Val Gly Ser Lys Pro Cys Pro Tyr Met Gln Tyr 450 455 460 tgc acc aag ctg tgg tgc acc ggg aag gcc aag gga cag atg gtg tgc 1440 Cys Thr Lys Leu Trp Cys Thr Gly Lys Ala Lys Gly Gln Met Val Cys 465 470 475 480 cag acc cgc cac ttc ccc tgg gcc gat ggc acc agc tgt ggc gag ggc 1488 Gln Thr Arg His Phe Pro Trp Ala Asp Gly Thr Ser Cys Gly Glu Gly 485 490 495 aag ctc tgc ctc aaa ggg gcc tgc gtg gag aga cac aac ctc aac aag 1536 Lys Leu Cys Leu Lys Gly Ala Cys Val Glu Arg His Asn Leu Asn Lys 500 505 510 cac agg gtg gat ggt tcc tgg gcc aaa tgg gat ccc tat ggc ccc tgc 1584 His Arg Val Asp Gly Ser Trp Ala Lys Trp Asp Pro Tyr Gly Pro Cys 515 520 525 tcg cgc aca tgt ggt ggg ggc gtg cag ctg gcc agg agg cag tgc acc 1632 Ser Arg Thr Cys Gly Gly Gly Val Gln Leu Ala Arg Arg Gln Cys Thr 530 535 540 aac ccc acc cct gcc aac ggg ggc aag tac tgc gag gga gtg agg gtg 1680 Asn Pro Thr Pro Ala Asn Gly Gly Lys Tyr Cys Glu Gly Val Arg Val 545 550 555 560 aaa tac cga tcc tgc aat ctg gag ccc tgc ccc agc tca gcc tcc gga 1728 Lys Tyr Arg Ser Cys Asn Leu Glu Pro Cys Pro Ser Ser Ala Ser Gly 565 570 575 aag agc ttc cgg gag gag cag tgt gag gct ttc aac ggc tac aac cac 1776 Lys Ser Phe Arg Glu Glu Gln Cys Glu Ala Phe Asn Gly Tyr Asn His 580 585 590 agc acc aac cgg ctc act ctc gcc gtg gca tgg gtg ccc aag tac tcc 1824 Ser Thr Asn Arg Leu Thr Leu Ala Val Ala Trp Val Pro Lys Tyr Ser 595 600 605 ggc gtg tct ccc cgg gac aag tgc aag ctc atc tgc cga gcc aat ggc 1872 Gly Val Ser Pro Arg Asp Lys Cys Lys Leu Ile Cys Arg Ala Asn Gly 610 615 620 act ggc tac ttc tat gtg ctg gca ccc aag gtg gtg gac ggc acg ctg 1920 Thr Gly Tyr Phe Tyr Val Leu Ala Pro Lys Val Val Asp Gly Thr Leu 625 630 635 640 tgc tct cct gac tcc acc tcc gtc tgt gtc caa ggc aag tgc atc aag 1968 Cys Ser Pro Asp Ser Thr Ser Val Cys Val Gln Gly Lys Cys Ile Lys 645 650 655 gct ggc tgt gat ggg aac ctg ggc tcc aag aag aga ttc gac aag tgt 2016 Ala Gly Cys Asp Gly Asn Leu Gly Ser Lys Lys Arg Phe Asp Lys Cys 660 665 670 ggg gtg tgt ggg gga gac aat aag agc tgc aag aag gtg act gga ctc 2064 Gly Val Cys Gly Gly Asp Asn Lys Ser Cys Lys Lys Val Thr Gly Leu 675 680 685 ttc acc aag ccc atg cat ggc tac aat ttc gtg gtg gcc atc ccc gca 2112 Phe Thr Lys Pro Met His Gly Tyr Asn Phe Val Val Ala Ile Pro Ala 690 695 700 ggc gcc tca agc atc gac atc cgc cag cgc ggt tac aaa ggg ctg atc 2160 Gly Ala Ser Ser Ile Asp Ile Arg Gln Arg Gly Tyr Lys Gly Leu Ile 705 710 715 720 ggg gat gac aac tac ctg gct ctg aag aac agc caa ggc aag tac ctg 2208 Gly Asp Asp Asn Tyr Leu Ala Leu Lys Asn Ser Gln Gly Lys Tyr Leu 725 730 735 ctc aac ggg cat ttc gtg gtg tcg gcg gtg gag cgg gac ctg gtg gtg 2256 Leu Asn Gly His Phe Val Val Ser Ala Val Glu Arg Asp Leu Val Val 740 745 750 aag ggc agt ctg ctg cgg tac agc ggc acg ggc aca gcg gtg gag agc 2304 Lys Gly Ser Leu Leu Arg Tyr Ser Gly Thr Gly Thr Ala Val Glu Ser 755 760 765 ctg cag gct tcc cgg ccc atc ctg gag ccg ctg acc gtg gag gtc ctc 2352 Leu Gln Ala Ser Arg Pro Ile Leu Glu Pro Leu Thr Val Glu Val Leu 770 775 780 tcc gtg ggg aag atg aca ccg ccc cgg gtc cgc tac tcc ttc tat ctg 2400 Ser Val Gly Lys Met Thr Pro Pro Arg Val Arg Tyr Ser Phe Tyr Leu 785 790 795 800 ccc aaa gag cct cgg gag gac aag tcc tct cat ccc aag gac ccc cgg 2448 Pro Lys Glu Pro Arg Glu Asp Lys Ser Ser His Pro Lys Asp Pro Arg 805 810 815 gga ccc tct gtc ttg cac aac agc gtc ctc agc ctc tcc aac cag gtg 2496 Gly Pro Ser Val Leu His Asn Ser Val Leu Ser Leu Ser Asn Gln Val 820 825 830 gag cag ccg gac gac agg ccc cct gca cgc tgg gtg gct ggc agc tgg 2544 Glu Gln Pro Asp Asp Arg Pro Pro Ala Arg Trp Val Ala Gly Ser Trp 835 840 845 ggg ccg tgc tcc gcg agc tgc ggc agt ggc ctg cag aag cgg gcg gtg 2592 Gly Pro Cys Ser Ala Ser Cys Gly Ser Gly Leu Gln Lys Arg Ala Val 850 855 860 gac tgc cgg ggc tcc gcc ggg cag cgc acg gtc cct gcc tgt gat gca 2640 Asp Cys Arg Gly Ser Ala Gly Gln Arg Thr Val Pro Ala Cys Asp Ala 865 870 875 880 gcc cat cgg ccc gtg gag aca caa gcc tgc ggg gag ccc tgc ccc acc 2688 Ala His Arg Pro Val Glu Thr Gln Ala Cys Gly Glu Pro Cys Pro Thr 885 890 895 tgg gag ctc agc gcc tgg tca ccc tgc tcc aag agc tgc ggc cgg gga 2736 Trp Glu Leu Ser Ala Trp Ser Pro Cys Ser Lys Ser Cys Gly Arg Gly 900 905 910 ttt cag agg cgc tca ctc aag tgt gtg ggc cac gga ggc cgg ctg ctg 2784 Phe Gln Arg Arg Ser Leu Lys Cys Val Gly His Gly Gly Arg Leu Leu 915 920 925 gcc cgg gac cag tgc aac ttg cac cgc aag ccc cag gag ctg gac ttc 2832 Ala Arg Asp Gln Cys Asn Leu

His Arg Lys Pro Gln Glu Leu Asp Phe 930 935 940 tgc gtc ctg agg ccg tgc tga 2853 Cys Val Leu Arg Pro Cys * 945 950 77 950 PRT Homo sapiens 77 Met Leu Leu Leu Gly Ile Leu Thr Leu Ala Phe Ala Gly Arg Thr Ala 1 5 10 15 Gly Gly Ser Glu Pro Glu Arg Glu Val Val Val Pro Ile Arg Leu Asp 20 25 30 Pro Asp Ile Asn Gly Arg Arg Tyr Tyr Trp Arg Gly Pro Glu Asp Ser 35 40 45 Gly Asp Gln Gly Leu Ile Phe Gln Ile Thr Ala Phe Gln Glu Asp Phe 50 55 60 Tyr Leu His Leu Thr Pro Asp Ala Gln Phe Leu Ala Pro Ala Phe Ser 65 70 75 80 Thr Glu His Leu Gly Val Pro Leu Gln Gly Leu Thr Gly Gly Ser Ser 85 90 95 Asp Leu Arg Arg Cys Phe Tyr Ser Gly Asp Val Asn Ala Glu Pro Asp 100 105 110 Ser Phe Ala Ala Val Ser Leu Cys Gly Gly Leu Arg Gly Ala Phe Gly 115 120 125 Tyr Arg Gly Ala Glu Tyr Val Ile Ser Pro Leu Pro Asn Ala Ser Ala 130 135 140 Pro Ala Ala Gln Arg Asn Ser Gln Gly Ala His Leu Leu Gln Arg Arg 145 150 155 160 Gly Val Pro Gly Gly Pro Ser Gly Asp Pro Thr Ser Arg Cys Gly Val 165 170 175 Ala Ser Gly Trp Asn Pro Ala Ile Leu Arg Ala Leu Asp Pro Tyr Lys 180 185 190 Pro Arg Arg Ala Gly Phe Gly Glu Ser Arg Ser Arg Arg Arg Ser Gly 195 200 205 Arg Ala Lys Arg Phe Val Ser Ile Pro Arg Tyr Val Glu Thr Leu Val 210 215 220 Val Ala Asp Glu Ser Met Val Lys Phe His Gly Ala Asp Leu Glu His 225 230 235 240 Tyr Leu Leu Thr Leu Leu Ala Thr Ala Ala Arg Leu Tyr Arg His Pro 245 250 255 Ser Ile Leu Asn Pro Ile Asn Ile Val Val Val Lys Val Leu Leu Leu 260 265 270 Arg Asp Arg Asp Ser Gly Pro Lys Val Thr Gly Asn Ala Ala Leu Thr 275 280 285 Leu Arg Asn Phe Cys Ala Trp Gln Lys Lys Leu Asn Lys Val Ser Asp 290 295 300 Lys His Pro Glu Tyr Trp Asp Thr Ala Ile Leu Phe Thr Arg Gln Asp 305 310 315 320 Leu Cys Gly Ala Thr Thr Cys Asp Thr Leu Gly Met Ala Asp Val Gly 325 330 335 Thr Met Cys Asp Pro Lys Arg Ser Cys Ser Val Ile Glu Asp Asp Gly 340 345 350 Leu Pro Ser Ala Phe Thr Thr Ala His Glu Leu Gly His Val Phe Asn 355 360 365 Met Pro His Asp Asn Val Lys Val Cys Glu Glu Val Phe Gly Lys Leu 370 375 380 Arg Ala Asn His Met Met Ser Pro Thr Leu Ile Gln Ile Asp Arg Ala 385 390 395 400 Asn Pro Trp Ser Ala Cys Ser Ala Ala Ile Ile Thr Asp Phe Leu Asp 405 410 415 Ser Gly His Gly Asp Cys Leu Leu Asp Gln Pro Ser Lys Pro Ile Ser 420 425 430 Leu Pro Glu Asp Leu Pro Gly Ala Ser Tyr Thr Leu Ser Gln Gln Cys 435 440 445 Glu Leu Ala Phe Gly Val Gly Ser Lys Pro Cys Pro Tyr Met Gln Tyr 450 455 460 Cys Thr Lys Leu Trp Cys Thr Gly Lys Ala Lys Gly Gln Met Val Cys 465 470 475 480 Gln Thr Arg His Phe Pro Trp Ala Asp Gly Thr Ser Cys Gly Glu Gly 485 490 495 Lys Leu Cys Leu Lys Gly Ala Cys Val Glu Arg His Asn Leu Asn Lys 500 505 510 His Arg Val Asp Gly Ser Trp Ala Lys Trp Asp Pro Tyr Gly Pro Cys 515 520 525 Ser Arg Thr Cys Gly Gly Gly Val Gln Leu Ala Arg Arg Gln Cys Thr 530 535 540 Asn Pro Thr Pro Ala Asn Gly Gly Lys Tyr Cys Glu Gly Val Arg Val 545 550 555 560 Lys Tyr Arg Ser Cys Asn Leu Glu Pro Cys Pro Ser Ser Ala Ser Gly 565 570 575 Lys Ser Phe Arg Glu Glu Gln Cys Glu Ala Phe Asn Gly Tyr Asn His 580 585 590 Ser Thr Asn Arg Leu Thr Leu Ala Val Ala Trp Val Pro Lys Tyr Ser 595 600 605 Gly Val Ser Pro Arg Asp Lys Cys Lys Leu Ile Cys Arg Ala Asn Gly 610 615 620 Thr Gly Tyr Phe Tyr Val Leu Ala Pro Lys Val Val Asp Gly Thr Leu 625 630 635 640 Cys Ser Pro Asp Ser Thr Ser Val Cys Val Gln Gly Lys Cys Ile Lys 645 650 655 Ala Gly Cys Asp Gly Asn Leu Gly Ser Lys Lys Arg Phe Asp Lys Cys 660 665 670 Gly Val Cys Gly Gly Asp Asn Lys Ser Cys Lys Lys Val Thr Gly Leu 675 680 685 Phe Thr Lys Pro Met His Gly Tyr Asn Phe Val Val Ala Ile Pro Ala 690 695 700 Gly Ala Ser Ser Ile Asp Ile Arg Gln Arg Gly Tyr Lys Gly Leu Ile 705 710 715 720 Gly Asp Asp Asn Tyr Leu Ala Leu Lys Asn Ser Gln Gly Lys Tyr Leu 725 730 735 Leu Asn Gly His Phe Val Val Ser Ala Val Glu Arg Asp Leu Val Val 740 745 750 Lys Gly Ser Leu Leu Arg Tyr Ser Gly Thr Gly Thr Ala Val Glu Ser 755 760 765 Leu Gln Ala Ser Arg Pro Ile Leu Glu Pro Leu Thr Val Glu Val Leu 770 775 780 Ser Val Gly Lys Met Thr Pro Pro Arg Val Arg Tyr Ser Phe Tyr Leu 785 790 795 800 Pro Lys Glu Pro Arg Glu Asp Lys Ser Ser His Pro Lys Asp Pro Arg 805 810 815 Gly Pro Ser Val Leu His Asn Ser Val Leu Ser Leu Ser Asn Gln Val 820 825 830 Glu Gln Pro Asp Asp Arg Pro Pro Ala Arg Trp Val Ala Gly Ser Trp 835 840 845 Gly Pro Cys Ser Ala Ser Cys Gly Ser Gly Leu Gln Lys Arg Ala Val 850 855 860 Asp Cys Arg Gly Ser Ala Gly Gln Arg Thr Val Pro Ala Cys Asp Ala 865 870 875 880 Ala His Arg Pro Val Glu Thr Gln Ala Cys Gly Glu Pro Cys Pro Thr 885 890 895 Trp Glu Leu Ser Ala Trp Ser Pro Cys Ser Lys Ser Cys Gly Arg Gly 900 905 910 Phe Gln Arg Arg Ser Leu Lys Cys Val Gly His Gly Gly Arg Leu Leu 915 920 925 Ala Arg Asp Gln Cys Asn Leu His Arg Lys Pro Gln Glu Leu Asp Phe 930 935 940 Cys Val Leu Arg Pro Cys 945 950 78 2853 DNA Homo sapiens CDS (1)...(2853) 78 atg ctt ctg ctg ggc atc cta acc ctg gct ttc gcc ggg cga acc gct 48 Met Leu Leu Leu Gly Ile Leu Thr Leu Ala Phe Ala Gly Arg Thr Ala 1 5 10 15 gga ggc tct gag cca gag cgg gag gta gtc gtt ccc atc cga ctg gac 96 Gly Gly Ser Glu Pro Glu Arg Glu Val Val Val Pro Ile Arg Leu Asp 20 25 30 ccg gac att aac ggc cgc cgc tac tac tgg cgg ggt ccc gag gac tcc 144 Pro Asp Ile Asn Gly Arg Arg Tyr Tyr Trp Arg Gly Pro Glu Asp Ser 35 40 45 ggg gat cag gga ctc att ttt cag atc aca gca ttt cag gag gac ttt 192 Gly Asp Gln Gly Leu Ile Phe Gln Ile Thr Ala Phe Gln Glu Asp Phe 50 55 60 tac cta cac ctg acg ccg gat gct cag ttc ttg gct ccc gcc ttc tcc 240 Tyr Leu His Leu Thr Pro Asp Ala Gln Phe Leu Ala Pro Ala Phe Ser 65 70 75 80 act gag cat ctg ggc gtc ccc ctc cag ggg ctc acc ggg ggc tct tca 288 Thr Glu His Leu Gly Val Pro Leu Gln Gly Leu Thr Gly Gly Ser Ser 85 90 95 gac ctg cga cgc tgc ttc tat tct ggg gac gtg aac gcc gag ccg gac 336 Asp Leu Arg Arg Cys Phe Tyr Ser Gly Asp Val Asn Ala Glu Pro Asp 100 105 110 tcg ttc gct gct gtg agc ctg tgc ggg ggg ctc cgc gga gcc ttt ggc 384 Ser Phe Ala Ala Val Ser Leu Cys Gly Gly Leu Arg Gly Ala Phe Gly 115 120 125 tac cga ggc gcc gag tat gtc att agc ccg ctg ccc aat gct agc gcg 432 Tyr Arg Gly Ala Glu Tyr Val Ile Ser Pro Leu Pro Asn Ala Ser Ala 130 135 140 ccg gcg gcg cag cgc aac agc cag ggc gca cac ctt ctc cag cgc cgg 480 Pro Ala Ala Gln Arg Asn Ser Gln Gly Ala His Leu Leu Gln Arg Arg 145 150 155 160 ggt gtt ccg ggc ggg cct tcc gga gac ccc acc tct cgc tgc ggg gtg 528 Gly Val Pro Gly Gly Pro Ser Gly Asp Pro Thr Ser Arg Cys Gly Val 165 170 175 gcc tcg ggc tgg aac ccc gcc atc cta cgg gcc ctg gac cct tac aag 576 Ala Ser Gly Trp Asn Pro Ala Ile Leu Arg Ala Leu Asp Pro Tyr Lys 180 185 190 ccg cgg cgg gcg ggc ttc ggg gag agt cgt agc cgg cgc agg tct ggg 624 Pro Arg Arg Ala Gly Phe Gly Glu Ser Arg Ser Arg Arg Arg Ser Gly 195 200 205 cgc gcc aag cgt ttc gtg tct atc ccg cgg tac gtg gag acg ctg gtg 672 Arg Ala Lys Arg Phe Val Ser Ile Pro Arg Tyr Val Glu Thr Leu Val 210 215 220 gtc gcg gac gag tca atg gtc aag ttc cac ggc gcg gac ctg gaa cat 720 Val Ala Asp Glu Ser Met Val Lys Phe His Gly Ala Asp Leu Glu His 225 230 235 240 tat ctg ctg acg ctg ctg gca acg gcg gcg cga ctc tac cgc cat ccc 768 Tyr Leu Leu Thr Leu Leu Ala Thr Ala Ala Arg Leu Tyr Arg His Pro 245 250 255 agc atc ctc aac ccc atc aac atc gtt gtg gtc aag gtg ctg ctt ctt 816 Ser Ile Leu Asn Pro Ile Asn Ile Val Val Val Lys Val Leu Leu Leu 260 265 270 aga gat cgt gac tcc ggg ccc aag gtc acc ggc aat gcg gcc ctg acg 864 Arg Asp Arg Asp Ser Gly Pro Lys Val Thr Gly Asn Ala Ala Leu Thr 275 280 285 ctg cgc aac ttc tgt gcc tgg cag aag aag ctg aac aaa gtg agt gac 912 Leu Arg Asn Phe Cys Ala Trp Gln Lys Lys Leu Asn Lys Val Ser Asp 290 295 300 aag cac ccc gag tac tgg gac act gcc atc ctc ttc acc agg cag gac 960 Lys His Pro Glu Tyr Trp Asp Thr Ala Ile Leu Phe Thr Arg Gln Asp 305 310 315 320 ctg tgt gga gcc acc acc tgt gac acc ctg ggc atg gct gat gtg ggt 1008 Leu Cys Gly Ala Thr Thr Cys Asp Thr Leu Gly Met Ala Asp Val Gly 325 330 335 acc atg tgt gac ccc aag aga agc tgc tct gtc att gag gac gat ggg 1056 Thr Met Cys Asp Pro Lys Arg Ser Cys Ser Val Ile Glu Asp Asp Gly 340 345 350 ctt cca tca gcc ttc acc act gcc cac gag ctg ggc cac gtg ttc aac 1104 Leu Pro Ser Ala Phe Thr Thr Ala His Glu Leu Gly His Val Phe Asn 355 360 365 atg ccc cat gac aat gtg aaa gtc tgt gag gag gtg ttt ggg aag ctc 1152 Met Pro His Asp Asn Val Lys Val Cys Glu Glu Val Phe Gly Lys Leu 370 375 380 cga gcc aac cac atg atg tcc ccg acc ctc atc cag atc gac cgt gcc 1200 Arg Ala Asn His Met Met Ser Pro Thr Leu Ile Gln Ile Asp Arg Ala 385 390 395 400 aac ccc tgg tca gcc tgc agt gct gcc atc atc acc gac ttc ctg gac 1248 Asn Pro Trp Ser Ala Cys Ser Ala Ala Ile Ile Thr Asp Phe Leu Asp 405 410 415 agc ggg cac ggt gac tgc ctc ctg gac caa ccc agc aag ccc atc tcc 1296 Ser Gly His Gly Asp Cys Leu Leu Asp Gln Pro Ser Lys Pro Ile Ser 420 425 430 ctg ccc gag gat ctg ccg ggc gcc agc tac acc ctg agc cag cag tgc 1344 Leu Pro Glu Asp Leu Pro Gly Ala Ser Tyr Thr Leu Ser Gln Gln Cys 435 440 445 gag ctg gct ttt ggc gtg ggc tcc aag ccc tgt cct tac atg cag tac 1392 Glu Leu Ala Phe Gly Val Gly Ser Lys Pro Cys Pro Tyr Met Gln Tyr 450 455 460 tgc acc aag ctg tgg tgc acc ggg aag gcc aag gga cag atg gtg tgc 1440 Cys Thr Lys Leu Trp Cys Thr Gly Lys Ala Lys Gly Gln Met Val Cys 465 470 475 480 cag acc cgc cac ttc ccc tgg gcc gat ggc acc agc tgt ggc gag ggc 1488 Gln Thr Arg His Phe Pro Trp Ala Asp Gly Thr Ser Cys Gly Glu Gly 485 490 495 aag ctc tgc ctc aaa ggg gcc tgc gtg gag aga cac aac ctc aac aag 1536 Lys Leu Cys Leu Lys Gly Ala Cys Val Glu Arg His Asn Leu Asn Lys 500 505 510 cac agg gtg gat ggt tcc tgg gcc aaa tgg gat ccc tat ggc ccc tgc 1584 His Arg Val Asp Gly Ser Trp Ala Lys Trp Asp Pro Tyr Gly Pro Cys 515 520 525 tcg cgc aca tgt ggt ggg ggc gtg cag ctg gcc agg agg cag tgc acc 1632 Ser Arg Thr Cys Gly Gly Gly Val Gln Leu Ala Arg Arg Gln Cys Thr 530 535 540 aac ccc acc cct gcc aac ggg ggc aag tac tgc gag gga gtg agg gtg 1680 Asn Pro Thr Pro Ala Asn Gly Gly Lys Tyr Cys Glu Gly Val Arg Val 545 550 555 560 aaa tac cga tcc tgc aat ctg gag ccc tgc ccc agc tca gcc tcc gga 1728 Lys Tyr Arg Ser Cys Asn Leu Glu Pro Cys Pro Ser Ser Ala Ser Gly 565 570 575 aag agc ttc cgg gag gag cag tgt gag gct ttc aac ggc tac aac cac 1776 Lys Ser Phe Arg Glu Glu Gln Cys Glu Ala Phe Asn Gly Tyr Asn His 580 585 590 agc acc aac cgg ctc act ctc gcc gtg gca tgg gtg ccc aag tac tcc 1824 Ser Thr Asn Arg Leu Thr Leu Ala Val Ala Trp Val Pro Lys Tyr Ser 595 600 605 ggc gtg tct ccc cgg gac aag tgc aag ctc atc tgc cga gcc aat ggc 1872 Gly Val Ser Pro Arg Asp Lys Cys Lys Leu Ile Cys Arg Ala Asn Gly 610 615 620 act ggc tac ttc tat gtg ctg gca ccc aag gtg gtg gac ggc acg ctg 1920 Thr Gly Tyr Phe Tyr Val Leu Ala Pro Lys Val Val Asp Gly Thr Leu 625 630 635 640 tgc tct cct gac tcc acc tcc gtc tgt gtc caa ggc aag tgc atc aag 1968 Cys Ser Pro Asp Ser Thr Ser Val Cys Val Gln Gly Lys Cys Ile Lys 645 650 655 gct ggc tgt gat ggg aac ctg ggc tcc aag aag aga ttc gac aag tgt 2016 Ala Gly Cys Asp Gly Asn Leu Gly Ser Lys Lys Arg Phe Asp Lys Cys 660 665 670 ggg gtg tgt ggg gga gac aat aag agc tgc aag aag gtg act gga ctc 2064 Gly Val Cys Gly Gly Asp Asn Lys Ser Cys Lys Lys Val Thr Gly Leu 675 680 685 ttc acc aag ccc atg cat ggc tac aat ttc gtg gtg gcc atc ccc gca 2112 Phe Thr Lys Pro Met His Gly Tyr Asn Phe Val Val Ala Ile Pro Ala 690 695 700 ggc gcc tca agc atc gac atc cgc cag cgc ggt tac aaa ggg ctg atc 2160 Gly Ala Ser Ser Ile Asp Ile Arg Gln Arg Gly Tyr Lys Gly Leu Ile 705 710 715 720 ggg gat gac aac tac ctg gct ctg aag aac agc caa ggc aag tac ctg 2208 Gly Asp Asp Asn Tyr Leu Ala Leu Lys Asn Ser Gln Gly Lys Tyr Leu 725 730 735 ctc aac ggg cat ttc gtg gtg tcg gcg gtg gag cgg gac ctg gtg gtg 2256 Leu Asn Gly His Phe Val Val Ser Ala Val Glu Arg Asp Leu Val Val 740 745 750 aag ggc agt ctg ctg cgg tac agc ggc acg ggc aca gcg gtg gag agc 2304 Lys Gly Ser Leu Leu Arg Tyr Ser Gly Thr Gly Thr Ala Val Glu Ser 755 760 765 ctg cag gct tcc cgg ccc atc ctg gag ccg ctg acc gtg gag gtc ctc 2352 Leu Gln Ala Ser Arg Pro Ile Leu Glu Pro Leu Thr Val Glu Val Leu 770 775 780 tcc gtg ggg aag atg aca ccg ccc cgg gtc cgc tac tcc ttc tat ctg 2400 Ser Val Gly Lys Met Thr Pro Pro Arg Val Arg Tyr Ser Phe Tyr Leu 785 790 795 800 ccc aaa gag cct cgg gag gac aag tcc tct cat ccc aag gac ccc cgg 2448 Pro Lys Glu Pro Arg Glu Asp Lys Ser Ser His Pro Lys Asp Pro Arg 805 810 815 gga ccc tct gtc ttg cac aac agc gtc ctc agc ctc tcc aac cag gtg 2496 Gly Pro Ser Val Leu His Asn Ser Val Leu Ser Leu Ser Asn Gln Val 820 825 830 gag cag ccg gac gac agg ccc cct gca cgc tgg gtg gct ggc agc tgg 2544 Glu Gln Pro Asp Asp Arg Pro Pro Ala Arg Trp Val Ala Gly Ser Trp 835 840 845 ggg ccg tgc tcc gcg agc tgc ggc agt ggc ctg cag aag cgg gcg gtg 2592 Gly Pro Cys Ser Ala Ser Cys Gly Ser Gly Leu Gln Lys Arg Ala Val 850 855 860 gac tgc cgg ggc tcc gcc ggg cag cgc acg gtc cct gcc tgt gat gca 2640 Asp Cys Arg Gly Ser Ala Gly Gln Arg Thr Val Pro Ala Cys Asp Ala 865 870 875 880 gcc cat cgg ccc gtg gag aca caa gcc tgc ggg gag ccc tgc ccc acc 2688 Ala His Arg Pro Val Glu Thr Gln Ala Cys Gly Glu Pro Cys Pro Thr 885 890 895 tgg gag ctc agc gcc tgg tca ccc tgc tcc aag agc tgc ggc cgg gga 2736 Trp Glu Leu Ser Ala Trp Ser Pro Cys Ser Lys Ser Cys Gly Arg Gly

900 905 910 ttt cag agg cgc tca ctc aag tgt gtg ggc cac gga ggc cgg ctg ctg 2784 Phe Gln Arg Arg Ser Leu Lys Cys Val Gly His Gly Gly Arg Leu Leu 915 920 925 gcc cgg gac cag tgc aac ttg cac cgc aag ccc cag gag ctg gac ttc 2832 Ala Arg Asp Gln Cys Asn Leu His Arg Lys Pro Gln Glu Leu Asp Phe 930 935 940 tgc gtc ctg agg ccg tgc tga 2853 Cys Val Leu Arg Pro Cys * 945 950 79 119 PRT Artificial Sequence Consensus amino acid sequence 79 His Leu Glu Lys Asn Arg Ser Leu Leu Ala Pro Asp Phe Thr Val Thr 1 5 10 15 Thr Tyr Asp Glu Asp Gly Thr Leu Val Thr Glu Glu Pro Leu Ile Gln 20 25 30 Asp Asp His Cys Tyr Tyr Gln Gly Tyr Val Glu Gly Tyr Pro Asn Ser 35 40 45 Ala Val Ser Leu Ser Thr Cys Ser Gly Gly Leu Arg Gly Ile Leu Gln 50 55 60 Leu Glu Asn Leu Ser Tyr Gly Ile Glu Pro Leu Glu Ser Ser Asp Gly 65 70 75 80 Phe Glu His Ile Ile Tyr Gln Ile Glu Asn Asp Lys Thr Glu Pro Ser 85 90 95 Pro Cys Gly Glu Cys Gly Ser Leu Ser Thr Ser Thr Asp Ser Ser Tyr 100 105 110 Gly Ile Arg Ser Ala Ser Pro 115 80 203 PRT Artificial Sequence Consensus amino acid sequence 80 Arg Tyr Ile Glu Leu Val Ile Val Val Asp His Gly Met Tyr Thr Lys 1 5 10 15 Tyr Gly Ser Asp Leu Asn Lys Ile Arg Gln Arg Val His Gln Ile Val 20 25 30 Asn Leu Val Asn Glu Ile Tyr Arg Pro Gln Leu Asn Ile Arg Val Val 35 40 45 Leu Val Gly Leu Glu Ile Trp Ser Asp Gly Asp Lys Ile Asn Val Gln 50 55 60 Ser Asp Ala Asn Asp Thr Leu His Ser Phe Gly Glu Trp Arg Glu Thr 65 70 75 80 Asp Leu Leu Lys Arg Lys Ser His Asp Asn Ala Gln Leu Leu Thr Gly 85 90 95 Ile Asp Phe Asp Gly Asn Thr Ile Gly Ala Ala Tyr Val Gly Gly Met 100 105 110 Cys Ser Pro Lys Arg Ser Val Gly Val Val Gln Asp His Ser Pro Ile 115 120 125 Val Leu Leu Val Ala Val Thr Met Ala His Glu Leu Gly His Asn Leu 130 135 140 Gly Met Thr His Asp Asp Lys Asn Lys Asp Gly Cys Thr Cys Pro Gly 145 150 155 160 Gly Gly Ser Cys Ile Met Asn Pro Val Ala Ser Ser Ser Pro Ser Lys 165 170 175 Lys Lys Phe Ser Asn Cys Ser Lys Asp Asp Tyr Gln Lys Phe Leu Thr 180 185 190 Lys Gln Lys Pro Gln Cys Leu Leu Asn Lys Pro 195 200 81 54 PRT Artificial Sequence Consensus amino acid sequence 81 Ser Pro Trp Ser Glu Trp Ser Pro Cys Ser Val Thr Cys Gly Lys Gly 1 5 10 15 Ile Arg Thr Arg Gln Arg Thr Cys Asn Ser Pro Ala Pro Gln Lys Lys 20 25 30 Gly Gly Lys Pro Cys Thr Gly Asp Ala Gln Glu Glu Thr Glu Ala Cys 35 40 45 Asp Met Met Asp Lys Cys 50 82 968 PRT Mus musculus 82 Met Gln Pro Lys Val Pro Leu Gly Ser Arg Lys Gln Lys Pro Cys Ser 1 5 10 15 Asp Met Gly Asp Val Gln Arg Ala Ala Arg Ser Arg Gly Ser Leu Ser 20 25 30 Ala His Met Leu Leu Leu Leu Leu Ala Ser Ile Thr Met Leu Leu Cys 35 40 45 Ala Arg Gly Ala His Gly Arg Pro Thr Glu Glu Asp Glu Glu Leu Val 50 55 60 Leu Pro Ser Leu Glu Arg Ala Pro Gly His Asp Ser Thr Thr Thr Arg 65 70 75 80 Leu Arg Leu Asp Ala Phe Gly Gln Gln Leu His Leu Lys Leu Gln Pro 85 90 95 Asp Ser Gly Phe Leu Ala Pro Gly Phe Thr Leu Gln Thr Val Gly Arg 100 105 110 Ser Pro Gly Ser Glu Ala Gln His Leu Asp Pro Thr Gly Asp Leu Ala 115 120 125 His Cys Phe Tyr Ser Gly Thr Val Asn Gly Asp Pro Gly Ser Ala Ala 130 135 140 Ala Leu Ser Leu Cys Glu Gly Val Arg Gly Ala Phe Tyr Leu Gln Gly 145 150 155 160 Glu Glu Phe Phe Ile Gln Pro Ala Pro Gly Val Ala Thr Glu Arg Leu 165 170 175 Ala Pro Ala Val Pro Glu Glu Glu Ser Ser Ala Arg Pro Gln Phe His 180 185 190 Ile Leu Arg Arg Arg Arg Arg Gly Ser Gly Gly Ala Lys Cys Gly Val 195 200 205 Met Asp Asp Glu Thr Leu Pro Thr Ser Asp Ser Arg Pro Glu Ser Gln 210 215 220 Asn Thr Arg Asn Gln Trp Pro Val Arg Asp Pro Thr Pro Gln Asp Ala 225 230 235 240 Gly Lys Pro Ser Gly Pro Gly Ser Ile Arg Lys Lys Arg Phe Val Ser 245 250 255 Ser Pro Arg Tyr Val Glu Thr Met Leu Val Ala Asp Gln Ser Met Ala 260 265 270 Asp Phe His Gly Ser Gly Leu Lys His Tyr Leu Leu Thr Leu Phe Ser 275 280 285 Val Ala Ala Arg Phe Tyr Lys His Pro Ser Ile Arg Asn Ser Ile Ser 290 295 300 Leu Val Val Val Lys Ile Leu Val Ile Tyr Glu Glu Gln Lys Gly Pro 305 310 315 320 Glu Val Thr Ser Asn Ala Ala Leu Thr Leu Arg Asn Phe Cys Asn Trp 325 330 335 Gln Lys Gln His Asn Ser Pro Ser Asp Arg Asp Pro Glu His Tyr Asp 340 345 350 Thr Ala Ile Leu Phe Thr Arg Gln Asp Leu Cys Gly Ser His Thr Cys 355 360 365 Asp Thr Leu Gly Met Ala Asp Val Gly Thr Val Cys Asp Pro Ser Arg 370 375 380 Ser Cys Ser Val Ile Glu Asp Asp Gly Leu Gln Ala Ala Phe Thr Thr 385 390 395 400 Ala His Glu Leu Gly His Val Phe Asn Met Pro His Asp Asp Ala Lys 405 410 415 His Cys Ala Ser Leu Asn Gly Val Thr Gly Asp Ser His Leu Met Ala 420 425 430 Ser Met Leu Ser Ser Leu Asp His Ser Gln Pro Trp Ser Pro Cys Ser 435 440 445 Ala Tyr Met Val Thr Ser Phe Leu Asp Asn Gly His Gly Glu Cys Leu 450 455 460 Met Asp Lys Pro Gln Asn Pro Ile Lys Leu Pro Ser Asp Leu Pro Gly 465 470 475 480 Thr Leu Tyr Asp Ala Asn Arg Gln Cys Gln Phe Thr Phe Gly Glu Glu 485 490 495 Ser Lys His Cys Pro Asp Ala Ala Ser Thr Cys Thr Thr Leu Trp Cys 500 505 510 Thr Gly Thr Ser Gly Gly Leu Leu Val Cys Gln Thr Lys His Phe Pro 515 520 525 Trp Ala Asp Gly Thr Ser Cys Gly Glu Gly Lys Trp Cys Val Ser Gly 530 535 540 Lys Cys Val Asn Lys Thr Asp Met Lys His Phe Ala Thr Pro Val His 545 550 555 560 Gly Ser Trp Gly Pro Trp Gly Pro Trp Gly Asp Cys Ser Arg Thr Cys 565 570 575 Gly Gly Gly Val Gln Tyr Thr Met Arg Glu Cys Asp Asn Pro Val Pro 580 585 590 Lys Asn Gly Gly Lys Tyr Cys Glu Gly Lys Arg Val Arg Tyr Arg Ser 595 600 605 Cys Asn Ile Glu Asp Cys Pro Asp Asn Asn Gly Lys Thr Phe Arg Glu 610 615 620 Glu Gln Cys Glu Ala His Asn Glu Phe Ser Lys Ala Ser Phe Gly Asn 625 630 635 640 Glu Pro Thr Val Glu Trp Thr Pro Lys Tyr Ala Gly Val Ser Pro Lys 645 650 655 Asp Arg Cys Lys Leu Thr Cys Glu Ala Lys Gly Ile Gly Tyr Phe Phe 660 665 670 Val Leu Gln Pro Lys Val Val Asp Gly Thr Pro Cys Ser Pro Asp Ser 675 680 685 Thr Ser Val Cys Val Gln Gly Gln Cys Val Lys Ala Gly Cys Asp Arg 690 695 700 Ile Ile Asp Ser Lys Lys Lys Phe Asp Lys Cys Gly Val Cys Gly Gly 705 710 715 720 Asn Gly Ser Thr Cys Lys Lys Met Ser Gly Ile Val Thr Ser Thr Arg 725 730 735 Pro Gly Tyr His Asp Ile Val Thr Ile Pro Ala Gly Ala Thr Asn Ile 740 745 750 Glu Val Lys His Arg Asn Gln Arg Gly Ser Arg Asn Asn Gly Ser Phe 755 760 765 Leu Ala Ile Arg Ala Ala Asp Gly Thr Tyr Ile Leu Asn Gly Asn Phe 770 775 780 Thr Leu Ser Thr Leu Glu Gln Asp Leu Thr Tyr Lys Gly Thr Val Leu 785 790 795 800 Arg Tyr Ser Gly Ser Ser Ala Ala Leu Glu Arg Ile Arg Ser Phe Ser 805 810 815 Pro Leu Lys Glu Pro Leu Thr Ile Gln Val Leu Met Val Gly His Ala 820 825 830 Leu Arg Pro Lys Ile Lys Phe Thr Tyr Phe Met Lys Lys Lys Thr Glu 835 840 845 Ser Phe Asn Ala Ile Pro Thr Phe Ser Glu Trp Val Ile Glu Glu Trp 850 855 860 Gly Glu Cys Ser Lys Thr Cys Gly Ser Gly Trp Gln Arg Arg Val Val 865 870 875 880 Gln Cys Arg Asp Ile Asn Gly His Pro Ala Ser Glu Cys Ala Lys Glu 885 890 895 Val Lys Pro Ala Ser Thr Arg Pro Cys Ala Asp Leu Pro Cys Pro His 900 905 910 Trp Gln Val Gly Asp Trp Ser Pro Cys Ser Lys Thr Cys Gly Lys Gly 915 920 925 Tyr Lys Lys Arg Thr Leu Lys Cys Val Ser His Asp Gly Gly Val Leu 930 935 940 Ser Asn Glu Ser Cys Asp Pro Leu Lys Lys Pro Lys His Tyr Ile Asp 945 950 955 960 Phe Cys Thr Leu Thr Gln Cys Ser 965 83 10 PRT Homo sapiens VARIANT (1)...(1) Xaa position one can be G or S or T or A or L or I or V or N VARIANT (2)...(3) Xaa = Any Amino Acid VARIANT (6)...(6) Xaa at position 6 can be L or I or V or M or F or Y or W VARIANT (7)...(7) Xaa at position 7 can be A, Q, N, L, G, S, V, T, I, M, F, Y, C, or W VARIANT (9)...(9) Xaa = Any Amino Acid VARIANT (10)...(10) Xaa at position 10 can be L or I or V or M or F or Y or W or G or S or P or Q 83 Xaa Xaa Xaa His Glu Xaa Xaa His Xaa Xaa 1 5 10 84 5 PRT Artificial Sequence Consensus amino acid sequence VARIANT (3)...(4) Xaa = Any Amino Acid 84 His Glu Xaa Xaa His 1 5 85 22 PRT Artificial Sequence Consensus amino acid sequence VARIANT (2)...(7) Xaa = Any Amino Acid VARIANT (9)...(14) Xaa = Any Amino Acid VARIANT (16)...(21) Xaa = Any Amino Acid 85 Leu Xaa Xaa Xaa Xaa Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa Xaa Leu Xaa 1 5 10 15 Xaa Xaa Xaa Xaa Xaa Leu 20 86 3445 DNA Homo sapiens CDS (83)...(3328) 86 cggccgcgga aagaatgcgc gccgcccgtg cgctccgcct gccgcgtctg gccacccgca 60 gccgccgcgt ccgcacctga cc atg gag tgc gcc ctc ctg ctc gcg tgt gcc 112 Met Glu Cys Ala Leu Leu Leu Ala Cys Ala 1 5 10 ttc ccg gct gcg ggt tcg ggc ccg ccg agg ggc ctg gcg gga ctg ggg 160 Phe Pro Ala Ala Gly Ser Gly Pro Pro Arg Gly Leu Ala Gly Leu Gly 15 20 25 cgc gtg gcc aag gcg ctc cag ctg tgc tgc ctc tgc tgt gcg tcg gtc 208 Arg Val Ala Lys Ala Leu Gln Leu Cys Cys Leu Cys Cys Ala Ser Val 30 35 40 gcc gcg gcc tta gcc agt gac agc agc agc ggc gcc agc gga tta aat 256 Ala Ala Ala Leu Ala Ser Asp Ser Ser Ser Gly Ala Ser Gly Leu Asn 45 50 55 gat gat tac gtc ttt gtc acg cca gta gaa gta gac tca gcc ggg tca 304 Asp Asp Tyr Val Phe Val Thr Pro Val Glu Val Asp Ser Ala Gly Ser 60 65 70 tat att tca cac gac att ttg cac aac ggc agg aaa aag cga tcg gcg 352 Tyr Ile Ser His Asp Ile Leu His Asn Gly Arg Lys Lys Arg Ser Ala 75 80 85 90 cag aat gcc aga agc tcc ctg cac tac cga ttt tca gca ttt gga cag 400 Gln Asn Ala Arg Ser Ser Leu His Tyr Arg Phe Ser Ala Phe Gly Gln 95 100 105 gaa ctg cac tta gaa ctt aag ccc tcg gcg att ttg agc agt cac ttt 448 Glu Leu His Leu Glu Leu Lys Pro Ser Ala Ile Leu Ser Ser His Phe 110 115 120 att gtc cag gta ctt gga aaa gat ggt gct tca gag act cag aaa ccc 496 Ile Val Gln Val Leu Gly Lys Asp Gly Ala Ser Glu Thr Gln Lys Pro 125 130 135 gag gtg cag caa tgc ttc tat cag gga ttt atc aga aat gac agc tcc 544 Glu Val Gln Gln Cys Phe Tyr Gln Gly Phe Ile Arg Asn Asp Ser Ser 140 145 150 tcc tct gtc gct gtg tct acg tgt gct ggc ttg tca ggt tta ata agg 592 Ser Ser Val Ala Val Ser Thr Cys Ala Gly Leu Ser Gly Leu Ile Arg 155 160 165 170 aca cga aaa aat gaa ttc ctc atc tcg cca tta cct cag ctt ctg gcc 640 Thr Arg Lys Asn Glu Phe Leu Ile Ser Pro Leu Pro Gln Leu Leu Ala 175 180 185 cag gaa cac aac tac agc tcc cct gcg ggt cac cat cct cac gta ctg 688 Gln Glu His Asn Tyr Ser Ser Pro Ala Gly His His Pro His Val Leu 190 195 200 tac aaa agg aca gca gag gag aag atc cag cgg tac cgt ggc tac ccc 736 Tyr Lys Arg Thr Ala Glu Glu Lys Ile Gln Arg Tyr Arg Gly Tyr Pro 205 210 215 ggc tct ggc cgg aat tat cct ggt tac tcc cca agt cac att ccc cat 784 Gly Ser Gly Arg Asn Tyr Pro Gly Tyr Ser Pro Ser His Ile Pro His 220 225 230 gca tct cag agt cga gag aca gag tat cac cat cga agg ttg caa aag 832 Ala Ser Gln Ser Arg Glu Thr Glu Tyr His His Arg Arg Leu Gln Lys 235 240 245 250 cag cat ttt tgt gga cga cgc aag aaa tat gct ccc aag cct ccc aca 880 Gln His Phe Cys Gly Arg Arg Lys Lys Tyr Ala Pro Lys Pro Pro Thr 255 260 265 gag gac acc tat cta agg ttt gat gaa tat ggg agc tct ggg cga ccc 928 Glu Asp Thr Tyr Leu Arg Phe Asp Glu Tyr Gly Ser Ser Gly Arg Pro 270 275 280 aga aga tca gct gga aaa tca caa aag ggc ctc aat gtg gaa acc ctc 976 Arg Arg Ser Ala Gly Lys Ser Gln Lys Gly Leu Asn Val Glu Thr Leu 285 290 295 gtg gtg gca gac aag aaa atg gtg gaa aag cat ggc aag gga aat gtc 1024 Val Val Ala Asp Lys Lys Met Val Glu Lys His Gly Lys Gly Asn Val 300 305 310 acc aca tac att ctc aca gta atg aag gtt tct ggc cta ttt aaa gat 1072 Thr Thr Tyr Ile Leu Thr Val Met Lys Val Ser Gly Leu Phe Lys Asp 315 320 325 330 ggg act att gga agt gac ata aac gtg gtt gtg gtg agc cta att ctt 1120 Gly Thr Ile Gly Ser Asp Ile Asn Val Val Val Val Ser Leu Ile Leu 335 340 345 ctg gaa caa gaa cct gga gga tta ttg atc aac cat cat gca gac cag 1168 Leu Glu Gln Glu Pro Gly Gly Leu Leu Ile Asn His His Ala Asp Gln 350 355 360 tct ctg aat agt ttt tgt caa tgg cag tct gcc ctc att gga aag aat 1216 Ser Leu Asn Ser Phe Cys Gln Trp Gln Ser Ala Leu Ile Gly Lys Asn 365 370 375 ggc aag aga cat gat cat gcc atc tta cta aca gga ttt gat att tgt 1264 Gly Lys Arg His Asp His Ala Ile Leu Leu Thr Gly Phe Asp Ile Cys 380 385 390 tct tgg aag aat gaa cca tgt gac act cta ggg ttt gcc ccc acc agt 1312 Ser Trp Lys Asn Glu Pro Cys Asp Thr Leu Gly Phe Ala Pro Thr Ser 395 400 405 410 gga atg tgc tct aag tac cga agt tgt acc atc aat gag gac aca gga 1360 Gly Met Cys Ser Lys Tyr Arg Ser Cys Thr Ile Asn Glu Asp Thr Gly 415 420 425 ctt ggc ctt gcc ttc acc atc gct cat gag tca ggg cac aac ttt ggt 1408 Leu Gly Leu Ala Phe Thr Ile Ala His Glu Ser Gly His Asn Phe Gly 430 435 440 atg att cac gac gga gaa ggg aat ccc tgc aga aag gct gaa ggc aat 1456 Met Ile His Asp Gly Glu Gly Asn Pro Cys Arg Lys Ala Glu Gly Asn 445 450 455 atc atg tct ccc aca ctg acc gga aac aat gga gtg ttt tca tgg tct 1504 Ile Met Ser Pro Thr Leu Thr Gly Asn Asn Gly Val Phe Ser Trp Ser 460 465 470 tcc tgc agc cgc cag tat ctc aag aaa ttc ctc agc aca cct cag gcg 1552 Ser Cys Ser Arg Gln Tyr Leu Lys Lys Phe Leu Ser Thr Pro Gln Ala 475 480 485 490 ggg tgt cta gtg gat gag ccc aag caa gca gga cag tat aaa tat ccg 1600 Gly Cys Leu Val Asp Glu Pro Lys Gln Ala Gly Gln Tyr Lys Tyr Pro 495 500 505 gac aaa cta cca gga cag att tat gat gct gac aca cag tgt aaa tgg 1648 Asp Lys Leu Pro Gly Gln Ile Tyr Asp Ala Asp Thr Gln Cys Lys Trp 510 515

520 caa ttt gga gca aaa gcc aag tta tgc agc ctt ggt ttt gtg aag gat 1696 Gln Phe Gly Ala Lys Ala Lys Leu Cys Ser Leu Gly Phe Val Lys Asp 525 530 535 att tgc aaa tca ctt tgg tgc cac cga gta ggc cac agg tgt gag acc 1744 Ile Cys Lys Ser Leu Trp Cys His Arg Val Gly His Arg Cys Glu Thr 540 545 550 aag ttt atg ccc gca gca gaa ggg acc gtt tgt ggc ttg agt atg tgg 1792 Lys Phe Met Pro Ala Ala Glu Gly Thr Val Cys Gly Leu Ser Met Trp 555 560 565 570 tgt cgg caa ggc cag tgc gta aag ttt ggg gag ctc ggg ccc cgg ccc 1840 Cys Arg Gln Gly Gln Cys Val Lys Phe Gly Glu Leu Gly Pro Arg Pro 575 580 585 atc cac ggc cag tgg tcc gcc tgg tcg aag tgg tca gaa tgt tcc cgg 1888 Ile His Gly Gln Trp Ser Ala Trp Ser Lys Trp Ser Glu Cys Ser Arg 590 595 600 aca tgt ggt gga gga gtc aag ttc cag gag aga cac tgc aat aac ccc 1936 Thr Cys Gly Gly Gly Val Lys Phe Gln Glu Arg His Cys Asn Asn Pro 605 610 615 aag cct cag tat ggt ggc ata ttc tgt cca ggt tct agc cgt att tat 1984 Lys Pro Gln Tyr Gly Gly Ile Phe Cys Pro Gly Ser Ser Arg Ile Tyr 620 625 630 cag ctg tgc aat att aac cct tgc aat gaa aat agc ttg gat ttt cgg 2032 Gln Leu Cys Asn Ile Asn Pro Cys Asn Glu Asn Ser Leu Asp Phe Arg 635 640 645 650 gct caa cag tgt gca gaa tat aac agc aaa cct ttc cgt gga tgg ttc 2080 Ala Gln Gln Cys Ala Glu Tyr Asn Ser Lys Pro Phe Arg Gly Trp Phe 655 660 665 tac cag tgg aaa ccc tat aca aaa gtg gaa gag gaa gat cga tgc aaa 2128 Tyr Gln Trp Lys Pro Tyr Thr Lys Val Glu Glu Glu Asp Arg Cys Lys 670 675 680 ctg tac tgc aag gct gag aac ttt gaa ttt ttt ttt gca atg tcc ggc 2176 Leu Tyr Cys Lys Ala Glu Asn Phe Glu Phe Phe Phe Ala Met Ser Gly 685 690 695 aaa gtg aaa gat gga act ccc tgc tcc cca aac aaa aat gat gtt tgt 2224 Lys Val Lys Asp Gly Thr Pro Cys Ser Pro Asn Lys Asn Asp Val Cys 700 705 710 att gac ggg gtt tgt gaa cta gtg gga tgt gat cat gaa cta ggc tct 2272 Ile Asp Gly Val Cys Glu Leu Val Gly Cys Asp His Glu Leu Gly Ser 715 720 725 730 aaa gca gtt tca gat gct tgt ggc gtt tgc aaa ggt gat aat tca act 2320 Lys Ala Val Ser Asp Ala Cys Gly Val Cys Lys Gly Asp Asn Ser Thr 735 740 745 tgc aag ttt tat aaa ggc ctg tac ctc aac cag cat aaa gca aat gaa 2368 Cys Lys Phe Tyr Lys Gly Leu Tyr Leu Asn Gln His Lys Ala Asn Glu 750 755 760 tat tat ccg gtg gtc ctc att cca gct ggc gcc cga agc atc gaa atc 2416 Tyr Tyr Pro Val Val Leu Ile Pro Ala Gly Ala Arg Ser Ile Glu Ile 765 770 775 cag gag ctg cag gtt tcc tcc agt tac ctc gca gtt cga agc ctc agt 2464 Gln Glu Leu Gln Val Ser Ser Ser Tyr Leu Ala Val Arg Ser Leu Ser 780 785 790 caa aag tat tac ctc acc ggg ggc tgg agc atc gac tgg cct ggg gag 2512 Gln Lys Tyr Tyr Leu Thr Gly Gly Trp Ser Ile Asp Trp Pro Gly Glu 795 800 805 810 ttc ccc ttc gct ggg acc acg ttt gaa tac cag cgc tct ttc aac cgc 2560 Phe Pro Phe Ala Gly Thr Thr Phe Glu Tyr Gln Arg Ser Phe Asn Arg 815 820 825 ccg gaa cgt ctg tac gcg cca ggg ccc aca aat gag acg ctg gtc ttt 2608 Pro Glu Arg Leu Tyr Ala Pro Gly Pro Thr Asn Glu Thr Leu Val Phe 830 835 840 gaa att ctg atg caa ggc aaa aat cca ggg ata gct tgg aag tat gca 2656 Glu Ile Leu Met Gln Gly Lys Asn Pro Gly Ile Ala Trp Lys Tyr Ala 845 850 855 ctt ccc aag gtc atg aat gga act cca cca gcc aca aaa aga cct gcc 2704 Leu Pro Lys Val Met Asn Gly Thr Pro Pro Ala Thr Lys Arg Pro Ala 860 865 870 tat acc tgg agt atc gtg cag tca gag tgc tcc gtc tcc tgt ggt gga 2752 Tyr Thr Trp Ser Ile Val Gln Ser Glu Cys Ser Val Ser Cys Gly Gly 875 880 885 890 ggt tac ata aat gta aag gcc att tgc ttg cga gat caa aat act caa 2800 Gly Tyr Ile Asn Val Lys Ala Ile Cys Leu Arg Asp Gln Asn Thr Gln 895 900 905 gtc aat tcc tca ttc tgc agt gca aaa acc aag cca gta act gag ccc 2848 Val Asn Ser Ser Phe Cys Ser Ala Lys Thr Lys Pro Val Thr Glu Pro 910 915 920 aaa atc tgc aac gct ttc tcc tgc ccg gct tac tgg atg cca ggt gaa 2896 Lys Ile Cys Asn Ala Phe Ser Cys Pro Ala Tyr Trp Met Pro Gly Glu 925 930 935 tgg agt aca tgc agc aag tcc tgt gct gga ggc cag cag agc cga aag 2944 Trp Ser Thr Cys Ser Lys Ser Cys Ala Gly Gly Gln Gln Ser Arg Lys 940 945 950 atc cag tgt gtg caa aag aag ccc ttc caa aag gag gaa gca gtg ttg 2992 Ile Gln Cys Val Gln Lys Lys Pro Phe Gln Lys Glu Glu Ala Val Leu 955 960 965 970 cat tct ctc tgt cca gta agc aca ccc act cag gtc caa gcc tgc aac 3040 His Ser Leu Cys Pro Val Ser Thr Pro Thr Gln Val Gln Ala Cys Asn 975 980 985 agc cat gcc tgc cct cca caa tgg agc ctt gga ccc tgg tct cag tgt 3088 Ser His Ala Cys Pro Pro Gln Trp Ser Leu Gly Pro Trp Ser Gln Cys 990 995 1000 tcc aag acc tgt gga cga ggg gtg agg aag cgt gaa ctc ctc tgc aag 3136 Ser Lys Thr Cys Gly Arg Gly Val Arg Lys Arg Glu Leu Leu Cys Lys 1005 1010 1015 ggc tct gcc gca gaa acc ctc ccc gag agc cag tgt acc agt ctc ccc 3184 Gly Ser Ala Ala Glu Thr Leu Pro Glu Ser Gln Cys Thr Ser Leu Pro 1020 1025 1030 aga cct gag ctg cag gag ggc tgt gtg ctt gga cga tgt ccc aag aac 3232 Arg Pro Glu Leu Gln Glu Gly Cys Val Leu Gly Arg Cys Pro Lys Asn 1035 1040 1045 1050 agc cgg cta cag tgg gtc gct tct tcg tgg agc gag gta tgg att aga 3280 Ser Arg Leu Gln Trp Val Ala Ser Ser Trp Ser Glu Val Trp Ile Arg 1055 1060 1065 agt cac tgc tgg gtc agg aga ttg aga cca tcc tgg cta aca cag tga 3328 Ser His Cys Trp Val Arg Arg Leu Arg Pro Ser Trp Leu Thr Gln * 1070 1075 1080 aaccctgtct ctactaaaaa tacaaaaaat tagccaggca aggtggcagg cgcctgtagt 3388 ctgatctact ggggctgtag tctgatctac tggggctgtt cttgggacat cgtcggg 3445 87 1081 PRT Homo sapiens 87 Met Glu Cys Ala Leu Leu Leu Ala Cys Ala Phe Pro Ala Ala Gly Ser 1 5 10 15 Gly Pro Pro Arg Gly Leu Ala Gly Leu Gly Arg Val Ala Lys Ala Leu 20 25 30 Gln Leu Cys Cys Leu Cys Cys Ala Ser Val Ala Ala Ala Leu Ala Ser 35 40 45 Asp Ser Ser Ser Gly Ala Ser Gly Leu Asn Asp Asp Tyr Val Phe Val 50 55 60 Thr Pro Val Glu Val Asp Ser Ala Gly Ser Tyr Ile Ser His Asp Ile 65 70 75 80 Leu His Asn Gly Arg Lys Lys Arg Ser Ala Gln Asn Ala Arg Ser Ser 85 90 95 Leu His Tyr Arg Phe Ser Ala Phe Gly Gln Glu Leu His Leu Glu Leu 100 105 110 Lys Pro Ser Ala Ile Leu Ser Ser His Phe Ile Val Gln Val Leu Gly 115 120 125 Lys Asp Gly Ala Ser Glu Thr Gln Lys Pro Glu Val Gln Gln Cys Phe 130 135 140 Tyr Gln Gly Phe Ile Arg Asn Asp Ser Ser Ser Ser Val Ala Val Ser 145 150 155 160 Thr Cys Ala Gly Leu Ser Gly Leu Ile Arg Thr Arg Lys Asn Glu Phe 165 170 175 Leu Ile Ser Pro Leu Pro Gln Leu Leu Ala Gln Glu His Asn Tyr Ser 180 185 190 Ser Pro Ala Gly His His Pro His Val Leu Tyr Lys Arg Thr Ala Glu 195 200 205 Glu Lys Ile Gln Arg Tyr Arg Gly Tyr Pro Gly Ser Gly Arg Asn Tyr 210 215 220 Pro Gly Tyr Ser Pro Ser His Ile Pro His Ala Ser Gln Ser Arg Glu 225 230 235 240 Thr Glu Tyr His His Arg Arg Leu Gln Lys Gln His Phe Cys Gly Arg 245 250 255 Arg Lys Lys Tyr Ala Pro Lys Pro Pro Thr Glu Asp Thr Tyr Leu Arg 260 265 270 Phe Asp Glu Tyr Gly Ser Ser Gly Arg Pro Arg Arg Ser Ala Gly Lys 275 280 285 Ser Gln Lys Gly Leu Asn Val Glu Thr Leu Val Val Ala Asp Lys Lys 290 295 300 Met Val Glu Lys His Gly Lys Gly Asn Val Thr Thr Tyr Ile Leu Thr 305 310 315 320 Val Met Lys Val Ser Gly Leu Phe Lys Asp Gly Thr Ile Gly Ser Asp 325 330 335 Ile Asn Val Val Val Val Ser Leu Ile Leu Leu Glu Gln Glu Pro Gly 340 345 350 Gly Leu Leu Ile Asn His His Ala Asp Gln Ser Leu Asn Ser Phe Cys 355 360 365 Gln Trp Gln Ser Ala Leu Ile Gly Lys Asn Gly Lys Arg His Asp His 370 375 380 Ala Ile Leu Leu Thr Gly Phe Asp Ile Cys Ser Trp Lys Asn Glu Pro 385 390 395 400 Cys Asp Thr Leu Gly Phe Ala Pro Thr Ser Gly Met Cys Ser Lys Tyr 405 410 415 Arg Ser Cys Thr Ile Asn Glu Asp Thr Gly Leu Gly Leu Ala Phe Thr 420 425 430 Ile Ala His Glu Ser Gly His Asn Phe Gly Met Ile His Asp Gly Glu 435 440 445 Gly Asn Pro Cys Arg Lys Ala Glu Gly Asn Ile Met Ser Pro Thr Leu 450 455 460 Thr Gly Asn Asn Gly Val Phe Ser Trp Ser Ser Cys Ser Arg Gln Tyr 465 470 475 480 Leu Lys Lys Phe Leu Ser Thr Pro Gln Ala Gly Cys Leu Val Asp Glu 485 490 495 Pro Lys Gln Ala Gly Gln Tyr Lys Tyr Pro Asp Lys Leu Pro Gly Gln 500 505 510 Ile Tyr Asp Ala Asp Thr Gln Cys Lys Trp Gln Phe Gly Ala Lys Ala 515 520 525 Lys Leu Cys Ser Leu Gly Phe Val Lys Asp Ile Cys Lys Ser Leu Trp 530 535 540 Cys His Arg Val Gly His Arg Cys Glu Thr Lys Phe Met Pro Ala Ala 545 550 555 560 Glu Gly Thr Val Cys Gly Leu Ser Met Trp Cys Arg Gln Gly Gln Cys 565 570 575 Val Lys Phe Gly Glu Leu Gly Pro Arg Pro Ile His Gly Gln Trp Ser 580 585 590 Ala Trp Ser Lys Trp Ser Glu Cys Ser Arg Thr Cys Gly Gly Gly Val 595 600 605 Lys Phe Gln Glu Arg His Cys Asn Asn Pro Lys Pro Gln Tyr Gly Gly 610 615 620 Ile Phe Cys Pro Gly Ser Ser Arg Ile Tyr Gln Leu Cys Asn Ile Asn 625 630 635 640 Pro Cys Asn Glu Asn Ser Leu Asp Phe Arg Ala Gln Gln Cys Ala Glu 645 650 655 Tyr Asn Ser Lys Pro Phe Arg Gly Trp Phe Tyr Gln Trp Lys Pro Tyr 660 665 670 Thr Lys Val Glu Glu Glu Asp Arg Cys Lys Leu Tyr Cys Lys Ala Glu 675 680 685 Asn Phe Glu Phe Phe Phe Ala Met Ser Gly Lys Val Lys Asp Gly Thr 690 695 700 Pro Cys Ser Pro Asn Lys Asn Asp Val Cys Ile Asp Gly Val Cys Glu 705 710 715 720 Leu Val Gly Cys Asp His Glu Leu Gly Ser Lys Ala Val Ser Asp Ala 725 730 735 Cys Gly Val Cys Lys Gly Asp Asn Ser Thr Cys Lys Phe Tyr Lys Gly 740 745 750 Leu Tyr Leu Asn Gln His Lys Ala Asn Glu Tyr Tyr Pro Val Val Leu 755 760 765 Ile Pro Ala Gly Ala Arg Ser Ile Glu Ile Gln Glu Leu Gln Val Ser 770 775 780 Ser Ser Tyr Leu Ala Val Arg Ser Leu Ser Gln Lys Tyr Tyr Leu Thr 785 790 795 800 Gly Gly Trp Ser Ile Asp Trp Pro Gly Glu Phe Pro Phe Ala Gly Thr 805 810 815 Thr Phe Glu Tyr Gln Arg Ser Phe Asn Arg Pro Glu Arg Leu Tyr Ala 820 825 830 Pro Gly Pro Thr Asn Glu Thr Leu Val Phe Glu Ile Leu Met Gln Gly 835 840 845 Lys Asn Pro Gly Ile Ala Trp Lys Tyr Ala Leu Pro Lys Val Met Asn 850 855 860 Gly Thr Pro Pro Ala Thr Lys Arg Pro Ala Tyr Thr Trp Ser Ile Val 865 870 875 880 Gln Ser Glu Cys Ser Val Ser Cys Gly Gly Gly Tyr Ile Asn Val Lys 885 890 895 Ala Ile Cys Leu Arg Asp Gln Asn Thr Gln Val Asn Ser Ser Phe Cys 900 905 910 Ser Ala Lys Thr Lys Pro Val Thr Glu Pro Lys Ile Cys Asn Ala Phe 915 920 925 Ser Cys Pro Ala Tyr Trp Met Pro Gly Glu Trp Ser Thr Cys Ser Lys 930 935 940 Ser Cys Ala Gly Gly Gln Gln Ser Arg Lys Ile Gln Cys Val Gln Lys 945 950 955 960 Lys Pro Phe Gln Lys Glu Glu Ala Val Leu His Ser Leu Cys Pro Val 965 970 975 Ser Thr Pro Thr Gln Val Gln Ala Cys Asn Ser His Ala Cys Pro Pro 980 985 990 Gln Trp Ser Leu Gly Pro Trp Ser Gln Cys Ser Lys Thr Cys Gly Arg 995 1000 1005 Gly Val Arg Lys Arg Glu Leu Leu Cys Lys Gly Ser Ala Ala Glu Thr 1010 1015 1020 Leu Pro Glu Ser Gln Cys Thr Ser Leu Pro Arg Pro Glu Leu Gln Glu 1025 1030 1035 1040 Gly Cys Val Leu Gly Arg Cys Pro Lys Asn Ser Arg Leu Gln Trp Val 1045 1050 1055 Ala Ser Ser Trp Ser Glu Val Trp Ile Arg Ser His Cys Trp Val Arg 1060 1065 1070 Arg Leu Arg Pro Ser Trp Leu Thr Gln 1075 1080 88 3246 DNA Homo sapiens CDS (1)...(3246) 88 atg gag tgc gcc ctc ctg ctc gcg tgt gcc ttc ccg gct gcg ggt tcg 48 Met Glu Cys Ala Leu Leu Leu Ala Cys Ala Phe Pro Ala Ala Gly Ser 1 5 10 15 ggc ccg ccg agg ggc ctg gcg gga ctg ggg cgc gtg gcc aag gcg ctc 96 Gly Pro Pro Arg Gly Leu Ala Gly Leu Gly Arg Val Ala Lys Ala Leu 20 25 30 cag ctg tgc tgc ctc tgc tgt gcg tcg gtc gcc gcg gcc tta gcc agt 144 Gln Leu Cys Cys Leu Cys Cys Ala Ser Val Ala Ala Ala Leu Ala Ser 35 40 45 gac agc agc agc ggc gcc agc gga tta aat gat gat tac gtc ttt gtc 192 Asp Ser Ser Ser Gly Ala Ser Gly Leu Asn Asp Asp Tyr Val Phe Val 50 55 60 acg cca gta gaa gta gac tca gcc ggg tca tat att tca cac gac att 240 Thr Pro Val Glu Val Asp Ser Ala Gly Ser Tyr Ile Ser His Asp Ile 65 70 75 80 ttg cac aac ggc agg aaa aag cga tcg gcg cag aat gcc aga agc tcc 288 Leu His Asn Gly Arg Lys Lys Arg Ser Ala Gln Asn Ala Arg Ser Ser 85 90 95 ctg cac tac cga ttt tca gca ttt gga cag gaa ctg cac tta gaa ctt 336 Leu His Tyr Arg Phe Ser Ala Phe Gly Gln Glu Leu His Leu Glu Leu 100 105 110 aag ccc tcg gcg att ttg agc agt cac ttt att gtc cag gta ctt gga 384 Lys Pro Ser Ala Ile Leu Ser Ser His Phe Ile Val Gln Val Leu Gly 115 120 125 aaa gat ggt gct tca gag act cag aaa ccc gag gtg cag caa tgc ttc 432 Lys Asp Gly Ala Ser Glu Thr Gln Lys Pro Glu Val Gln Gln Cys Phe 130 135 140 tat cag gga ttt atc aga aat gac agc tcc tcc tct gtc gct gtg tct 480 Tyr Gln Gly Phe Ile Arg Asn Asp Ser Ser Ser Ser Val Ala Val Ser 145 150 155 160 acg tgt gct ggc ttg tca ggt tta ata agg aca cga aaa aat gaa ttc 528 Thr Cys Ala Gly Leu Ser Gly Leu Ile Arg Thr Arg Lys Asn Glu Phe 165 170 175 ctc atc tcg cca tta cct cag ctt ctg gcc cag gaa cac aac tac agc 576 Leu Ile Ser Pro Leu Pro Gln Leu Leu Ala Gln Glu His Asn Tyr Ser 180 185 190 tcc cct gcg ggt cac cat cct cac gta ctg tac aaa agg aca gca gag 624 Ser Pro Ala Gly His His Pro His Val Leu Tyr Lys Arg Thr Ala Glu 195 200 205 gag aag atc cag cgg tac cgt ggc tac ccc ggc tct ggc cgg aat tat 672 Glu Lys Ile Gln Arg Tyr Arg Gly Tyr Pro Gly Ser Gly Arg Asn Tyr 210 215 220 cct ggt tac tcc cca agt cac att ccc cat gca tct cag agt cga gag 720 Pro Gly Tyr Ser Pro Ser His Ile Pro His Ala Ser Gln Ser Arg Glu 225 230 235 240 aca gag tat cac cat cga agg ttg caa aag cag cat ttt tgt gga cga 768 Thr Glu Tyr His His Arg Arg Leu Gln Lys Gln His Phe Cys Gly Arg 245 250 255 cgc aag aaa tat gct ccc aag cct ccc aca gag gac acc tat cta agg 816 Arg Lys Lys Tyr Ala Pro Lys Pro Pro Thr Glu Asp Thr Tyr Leu Arg

260 265 270 ttt gat gaa tat ggg agc tct ggg cga ccc aga aga tca gct gga aaa 864 Phe Asp Glu Tyr Gly Ser Ser Gly Arg Pro Arg Arg Ser Ala Gly Lys 275 280 285 tca caa aag ggc ctc aat gtg gaa acc ctc gtg gtg gca gac aag aaa 912 Ser Gln Lys Gly Leu Asn Val Glu Thr Leu Val Val Ala Asp Lys Lys 290 295 300 atg gtg gaa aag cat ggc aag gga aat gtc acc aca tac att ctc aca 960 Met Val Glu Lys His Gly Lys Gly Asn Val Thr Thr Tyr Ile Leu Thr 305 310 315 320 gta atg aag gtt tct ggc cta ttt aaa gat ggg act att gga agt gac 1008 Val Met Lys Val Ser Gly Leu Phe Lys Asp Gly Thr Ile Gly Ser Asp 325 330 335 ata aac gtg gtt gtg gtg agc cta att ctt ctg gaa caa gaa cct gga 1056 Ile Asn Val Val Val Val Ser Leu Ile Leu Leu Glu Gln Glu Pro Gly 340 345 350 gga tta ttg atc aac cat cat gca gac cag tct ctg aat agt ttt tgt 1104 Gly Leu Leu Ile Asn His His Ala Asp Gln Ser Leu Asn Ser Phe Cys 355 360 365 caa tgg cag tct gcc ctc att gga aag aat ggc aag aga cat gat cat 1152 Gln Trp Gln Ser Ala Leu Ile Gly Lys Asn Gly Lys Arg His Asp His 370 375 380 gcc atc tta cta aca gga ttt gat att tgt tct tgg aag aat gaa cca 1200 Ala Ile Leu Leu Thr Gly Phe Asp Ile Cys Ser Trp Lys Asn Glu Pro 385 390 395 400 tgt gac act cta ggg ttt gcc ccc acc agt gga atg tgc tct aag tac 1248 Cys Asp Thr Leu Gly Phe Ala Pro Thr Ser Gly Met Cys Ser Lys Tyr 405 410 415 cga agt tgt acc atc aat gag gac aca gga ctt ggc ctt gcc ttc acc 1296 Arg Ser Cys Thr Ile Asn Glu Asp Thr Gly Leu Gly Leu Ala Phe Thr 420 425 430 atc gct cat gag tca ggg cac aac ttt ggt atg att cac gac gga gaa 1344 Ile Ala His Glu Ser Gly His Asn Phe Gly Met Ile His Asp Gly Glu 435 440 445 ggg aat ccc tgc aga aag gct gaa ggc aat atc atg tct ccc aca ctg 1392 Gly Asn Pro Cys Arg Lys Ala Glu Gly Asn Ile Met Ser Pro Thr Leu 450 455 460 acc gga aac aat gga gtg ttt tca tgg tct tcc tgc agc cgc cag tat 1440 Thr Gly Asn Asn Gly Val Phe Ser Trp Ser Ser Cys Ser Arg Gln Tyr 465 470 475 480 ctc aag aaa ttc ctc agc aca cct cag gcg ggg tgt cta gtg gat gag 1488 Leu Lys Lys Phe Leu Ser Thr Pro Gln Ala Gly Cys Leu Val Asp Glu 485 490 495 ccc aag caa gca gga cag tat aaa tat ccg gac aaa cta cca gga cag 1536 Pro Lys Gln Ala Gly Gln Tyr Lys Tyr Pro Asp Lys Leu Pro Gly Gln 500 505 510 att tat gat gct gac aca cag tgt aaa tgg caa ttt gga gca aaa gcc 1584 Ile Tyr Asp Ala Asp Thr Gln Cys Lys Trp Gln Phe Gly Ala Lys Ala 515 520 525 aag tta tgc agc ctt ggt ttt gtg aag gat att tgc aaa tca ctt tgg 1632 Lys Leu Cys Ser Leu Gly Phe Val Lys Asp Ile Cys Lys Ser Leu Trp 530 535 540 tgc cac cga gta ggc cac agg tgt gag acc aag ttt atg ccc gca gca 1680 Cys His Arg Val Gly His Arg Cys Glu Thr Lys Phe Met Pro Ala Ala 545 550 555 560 gaa ggg acc gtt tgt ggc ttg agt atg tgg tgt cgg caa ggc cag tgc 1728 Glu Gly Thr Val Cys Gly Leu Ser Met Trp Cys Arg Gln Gly Gln Cys 565 570 575 gta aag ttt ggg gag ctc ggg ccc cgg ccc atc cac ggc cag tgg tcc 1776 Val Lys Phe Gly Glu Leu Gly Pro Arg Pro Ile His Gly Gln Trp Ser 580 585 590 gcc tgg tcg aag tgg tca gaa tgt tcc cgg aca tgt ggt gga gga gtc 1824 Ala Trp Ser Lys Trp Ser Glu Cys Ser Arg Thr Cys Gly Gly Gly Val 595 600 605 aag ttc cag gag aga cac tgc aat aac ccc aag cct cag tat ggt ggc 1872 Lys Phe Gln Glu Arg His Cys Asn Asn Pro Lys Pro Gln Tyr Gly Gly 610 615 620 ata ttc tgt cca ggt tct agc cgt att tat cag ctg tgc aat att aac 1920 Ile Phe Cys Pro Gly Ser Ser Arg Ile Tyr Gln Leu Cys Asn Ile Asn 625 630 635 640 cct tgc aat gaa aat agc ttg gat ttt cgg gct caa cag tgt gca gaa 1968 Pro Cys Asn Glu Asn Ser Leu Asp Phe Arg Ala Gln Gln Cys Ala Glu 645 650 655 tat aac agc aaa cct ttc cgt gga tgg ttc tac cag tgg aaa ccc tat 2016 Tyr Asn Ser Lys Pro Phe Arg Gly Trp Phe Tyr Gln Trp Lys Pro Tyr 660 665 670 aca aaa gtg gaa gag gaa gat cga tgc aaa ctg tac tgc aag gct gag 2064 Thr Lys Val Glu Glu Glu Asp Arg Cys Lys Leu Tyr Cys Lys Ala Glu 675 680 685 aac ttt gaa ttt ttt ttt gca atg tcc ggc aaa gtg aaa gat gga act 2112 Asn Phe Glu Phe Phe Phe Ala Met Ser Gly Lys Val Lys Asp Gly Thr 690 695 700 ccc tgc tcc cca aac aaa aat gat gtt tgt att gac ggg gtt tgt gaa 2160 Pro Cys Ser Pro Asn Lys Asn Asp Val Cys Ile Asp Gly Val Cys Glu 705 710 715 720 cta gtg gga tgt gat cat gaa cta ggc tct aaa gca gtt tca gat gct 2208 Leu Val Gly Cys Asp His Glu Leu Gly Ser Lys Ala Val Ser Asp Ala 725 730 735 tgt ggc gtt tgc aaa ggt gat aat tca act tgc aag ttt tat aaa ggc 2256 Cys Gly Val Cys Lys Gly Asp Asn Ser Thr Cys Lys Phe Tyr Lys Gly 740 745 750 ctg tac ctc aac cag cat aaa gca aat gaa tat tat ccg gtg gtc ctc 2304 Leu Tyr Leu Asn Gln His Lys Ala Asn Glu Tyr Tyr Pro Val Val Leu 755 760 765 att cca gct ggc gcc cga agc atc gaa atc cag gag ctg cag gtt tcc 2352 Ile Pro Ala Gly Ala Arg Ser Ile Glu Ile Gln Glu Leu Gln Val Ser 770 775 780 tcc agt tac ctc gca gtt cga agc ctc agt caa aag tat tac ctc acc 2400 Ser Ser Tyr Leu Ala Val Arg Ser Leu Ser Gln Lys Tyr Tyr Leu Thr 785 790 795 800 ggg ggc tgg agc atc gac tgg cct ggg gag ttc ccc ttc gct ggg acc 2448 Gly Gly Trp Ser Ile Asp Trp Pro Gly Glu Phe Pro Phe Ala Gly Thr 805 810 815 acg ttt gaa tac cag cgc tct ttc aac cgc ccg gaa cgt ctg tac gcg 2496 Thr Phe Glu Tyr Gln Arg Ser Phe Asn Arg Pro Glu Arg Leu Tyr Ala 820 825 830 cca ggg ccc aca aat gag acg ctg gtc ttt gaa att ctg atg caa ggc 2544 Pro Gly Pro Thr Asn Glu Thr Leu Val Phe Glu Ile Leu Met Gln Gly 835 840 845 aaa aat cca ggg ata gct tgg aag tat gca ctt ccc aag gtc atg aat 2592 Lys Asn Pro Gly Ile Ala Trp Lys Tyr Ala Leu Pro Lys Val Met Asn 850 855 860 gga act cca cca gcc aca aaa aga cct gcc tat acc tgg agt atc gtg 2640 Gly Thr Pro Pro Ala Thr Lys Arg Pro Ala Tyr Thr Trp Ser Ile Val 865 870 875 880 cag tca gag tgc tcc gtc tcc tgt ggt gga ggt tac ata aat gta aag 2688 Gln Ser Glu Cys Ser Val Ser Cys Gly Gly Gly Tyr Ile Asn Val Lys 885 890 895 gcc att tgc ttg cga gat caa aat act caa gtc aat tcc tca ttc tgc 2736 Ala Ile Cys Leu Arg Asp Gln Asn Thr Gln Val Asn Ser Ser Phe Cys 900 905 910 agt gca aaa acc aag cca gta act gag ccc aaa atc tgc aac gct ttc 2784 Ser Ala Lys Thr Lys Pro Val Thr Glu Pro Lys Ile Cys Asn Ala Phe 915 920 925 tcc tgc ccg gct tac tgg atg cca ggt gaa tgg agt aca tgc agc aag 2832 Ser Cys Pro Ala Tyr Trp Met Pro Gly Glu Trp Ser Thr Cys Ser Lys 930 935 940 tcc tgt gct gga ggc cag cag agc cga aag atc cag tgt gtg caa aag 2880 Ser Cys Ala Gly Gly Gln Gln Ser Arg Lys Ile Gln Cys Val Gln Lys 945 950 955 960 aag ccc ttc caa aag gag gaa gca gtg ttg cat tct ctc tgt cca gta 2928 Lys Pro Phe Gln Lys Glu Glu Ala Val Leu His Ser Leu Cys Pro Val 965 970 975 agc aca ccc act cag gtc caa gcc tgc aac agc cat gcc tgc cct cca 2976 Ser Thr Pro Thr Gln Val Gln Ala Cys Asn Ser His Ala Cys Pro Pro 980 985 990 caa tgg agc ctt gga ccc tgg tct cag tgt tcc aag acc tgt gga cga 3024 Gln Trp Ser Leu Gly Pro Trp Ser Gln Cys Ser Lys Thr Cys Gly Arg 995 1000 1005 ggg gtg agg aag cgt gaa ctc ctc tgc aag ggc tct gcc gca gaa acc 3072 Gly Val Arg Lys Arg Glu Leu Leu Cys Lys Gly Ser Ala Ala Glu Thr 1010 1015 1020 ctc ccc gag agc cag tgt acc agt ctc ccc aga cct gag ctg cag gag 3120 Leu Pro Glu Ser Gln Cys Thr Ser Leu Pro Arg Pro Glu Leu Gln Glu 1025 1030 1035 1040 ggc tgt gtg ctt gga cga tgt ccc aag aac agc cgg cta cag tgg gtc 3168 Gly Cys Val Leu Gly Arg Cys Pro Lys Asn Ser Arg Leu Gln Trp Val 1045 1050 1055 gct tct tcg tgg agc gag gta tgg att aga agt cac tgc tgg gtc agg 3216 Ala Ser Ser Trp Ser Glu Val Trp Ile Arg Ser His Cys Trp Val Arg 1060 1065 1070 aga ttg aga cca tcc tgg cta aca cag tga 3246 Arg Leu Arg Pro Ser Trp Leu Thr Gln * 1075 1080 89 119 PRT Artificial Sequence Consensus amino acid sequence 89 His Leu Glu Lys Asn Arg Ser Leu Leu Ala Pro Asp Phe Thr Val Thr 1 5 10 15 Thr Tyr Asp Glu Asp Gly Thr Leu Val Thr Glu Glu Pro Leu Ile Gln 20 25 30 Asp Asp His Cys Tyr Tyr Gln Gly Tyr Val Glu Gly Tyr Pro Asn Ser 35 40 45 Ala Val Ser Leu Ser Thr Cys Ser Gly Gly Leu Arg Gly Ile Leu Gln 50 55 60 Leu Glu Asn Leu Ser Tyr Gly Ile Glu Pro Leu Glu Ser Ser Asp Gly 65 70 75 80 Phe Glu His Ile Ile Tyr Gln Ile Glu Asn Asp Lys Thr Glu Pro Ser 85 90 95 Pro Cys Gly Glu Cys Gly Ser Leu Ser Thr Ser Thr Asp Ser Ser Tyr 100 105 110 Gly Ile Arg Ser Ala Ser Pro 115 90 187 PRT Artificial Sequence Consensus amino acid sequence 90 Tyr Gly Ser Asp Leu Asn Lys Ile Arg Gln Arg Val His Gln Ile Val 1 5 10 15 Asn Leu Val Asn Glu Ile Tyr Arg Pro Gln Leu Asn Ile Arg Val Val 20 25 30 Leu Val Gly Leu Glu Ile Trp Ser Asp Gly Asp Lys Ile Asn Val Gln 35 40 45 Ser Asp Ala Asn Asp Thr Leu His Ser Phe Gly Glu Trp Arg Glu Thr 50 55 60 Asp Leu Leu Lys Arg Lys Ser His Asp Asn Ala Gln Leu Leu Thr Gly 65 70 75 80 Ile Asp Phe Asp Gly Asn Thr Ile Gly Ala Ala Tyr Val Gly Gly Met 85 90 95 Cys Ser Pro Lys Arg Ser Val Gly Val Val Gln Asp His Ser Pro Ile 100 105 110 Val Leu Leu Val Ala Val Thr Met Ala His Glu Leu Gly His Asn Leu 115 120 125 Gly Met Thr His Asp Asp Lys Asn Lys Asp Gly Cys Thr Cys Glu Gly 130 135 140 Gly Gly Ser Cys Ile Met Asn Pro Val Ala Ser Ser Ser Pro Ser Lys 145 150 155 160 Lys Lys Phe Ser Asn Cys Ser Lys Asp Asp Tyr Gln Lys Phe Leu Thr 165 170 175 Lys Gln Lys Pro Gln Cys Leu Leu Asn Lys Pro 180 185 91 1311 PRT Homo sapiens 91 Met Arg Leu Leu Leu Leu Val Pro Leu Leu Leu Ala Pro Ala Pro Gly 1 5 10 15 Ser Ser Ala Pro Lys Val Arg Arg Gln Ser Asp Thr Trp Gly Pro Trp 20 25 30 Ser Gln Trp Ser Pro Cys Ser Arg Thr Cys Gly Gly Gly Val Ser Phe 35 40 45 Arg Glu Arg Pro Cys Tyr Ser Gln Arg Arg Asp Gly Gly Ser Ser Cys 50 55 60 Val Gly Pro Ala Arg Ser His Arg Ser Cys Arg Thr Glu Ser Cys Pro 65 70 75 80 Asp Gly Ala Arg Asp Phe Arg Ala Glu Gln Cys Ala Glu Phe Asp Gly 85 90 95 Ala Glu Phe Gln Gly Arg Arg Tyr Arg Trp Leu Pro Tyr Tyr Ser Ala 100 105 110 Pro Asn Lys Cys Glu Leu Asn Cys Ile Pro Lys Gly Glu Asn Phe Tyr 115 120 125 Tyr Lys His Arg Glu Ala Val Val Asp Gly Thr Pro Cys Glu Pro Gly 130 135 140 Lys Arg Asp Val Cys Val Asp Gly Ser Cys Arg Val Val Gly Cys Asp 145 150 155 160 His Glu Leu Asp Ser Ser Lys Gln Glu Asp Lys Cys Leu Arg Cys Gly 165 170 175 Gly Asp Gly Thr Cys Tyr Pro Val Ala Gly Thr Phe Asp Ala Asn Asp 180 185 190 Leu Ser Arg Gly Tyr Asn Gln Ile Leu Ile Val Pro Met Gly Ala Thr 195 200 205 Ser Ile Leu Ile Asp Glu Ala Ala Ala Ser Arg Asn Phe Leu Ala Val 210 215 220 Lys Asn Val Arg Gly Glu Tyr Tyr Leu Asn Gly His Trp Thr Ile Glu 225 230 235 240 Ala Ala Arg Ala Leu Pro Ala Ala Ser Thr Ile Leu His Tyr Glu Arg 245 250 255 Gly Ala Glu Gly Asp Leu Ala Pro Glu Arg Leu His Ala Arg Gly Pro 260 265 270 Thr Ser Glu Pro Leu Val Ile Glu Leu Ile Ser Gln Glu Pro Asn Pro 275 280 285 Gly Val His Tyr Glu Tyr His Leu Pro Leu Arg Arg Pro Ser Pro Gly 290 295 300 Phe Ser Trp Ser His Gly Ser Trp Ser Asp Cys Ser Ala Glu Cys Gly 305 310 315 320 Gly Gly His Gln Ser Arg Leu Val Phe Cys Thr Ile Asp His Glu Ala 325 330 335 Tyr Pro Asp His Met Cys Gln Arg Gln Pro Arg Pro Ala Asp Arg Arg 340 345 350 Ser Cys Asn Leu His Pro Cys Pro Glu Thr Lys Arg Thr Ser Tyr Leu 355 360 365 His Arg Pro Gly Ala Trp Arg Leu Ala Gly Ala Gln Arg Val Cys Gly 370 375 380 Asn Ser Trp Lys Ala Gly Pro Trp Ala Pro Cys Ser Ala Ser Cys Gly 385 390 395 400 Gly Gly Ser Gln Ser Arg Ser Val Tyr Cys Ile Ser Ser Asp Gly Ala 405 410 415 Gly Ile Gln Glu Ala Val Glu Glu Ala Glu Cys Ala Gly Leu Pro Gly 420 425 430 Lys Pro Pro Ala Ile Gln Ala Cys Asn Leu Gln Arg Cys Ala Ala Trp 435 440 445 Ser Pro Glu Pro Trp Gly Glu Cys Ser Val Ser Cys Gly Val Gly Val 450 455 460 Arg Lys Arg Ser Val Thr Cys Arg Gly Glu Arg Gly Ser Leu Leu His 465 470 475 480 Thr Ala Ala Cys Ser Leu Glu Asp Arg Pro Pro Leu Thr Glu Pro Cys 485 490 495 Val His Glu Asp Cys Pro Leu Leu Ser Asp Gln Ala Trp His Val Gly 500 505 510 Thr Trp Gly Leu Cys Ser Lys Ser Cys Ser Ser Gly Thr Arg Arg Arg 515 520 525 Gln Val Ile Cys Ala Ile Gly Pro Pro Ser His Cys Gly Ser Leu Gln 530 535 540 His Ser Lys Pro Val Asp Val Glu Pro Cys Asn Thr Gln Pro Cys His 545 550 555 560 Leu Pro Gln Glu Val Pro Ser Met Gln Asp Val His Thr Pro Ala Ser 565 570 575 Asn Pro Trp Met Pro Leu Gly Pro Gln Glu Ser Pro Ala Ser Ala Ala 580 585 590 Pro Ile Pro Ala Thr Pro Ala Val Gly Leu Arg Ala Pro Arg Leu Gln 595 600 605 Thr Gln Ser Ser Arg Val Leu Pro Arg Trp Pro His Gly Ile Ser Arg 610 615 620 Ala Ser Val Ala Arg Leu Pro Trp Gly Pro Leu Ser Ala Glu Gln Val 625 630 635 640 His Asn Thr His Gln Pro Gln Ala Gln Gln Asn Glu Pro Ser Glu Cys 645 650 655 Arg Gly Asp Thr Tyr Leu Arg Phe Asp Glu Tyr Gly Ser Ser Gly Arg 660 665 670 Pro Arg Arg Ser Ala Gly Lys Ser Gln Lys Gly Leu Asn Val Glu Thr 675 680 685 Leu Val Val Ala Asp Lys Lys Met Val Glu Lys His Gly Lys Gly Ser 690 695 700 Gln Phe Gly Cys Cys Tyr Asp Asn Val Ala Thr Ala Ala Gly Pro Leu 705 710 715 720 Gly Glu Gly Cys Val Gly Gln Pro Ser His Ala Tyr Pro Val Arg Cys 725 730 735 Leu Leu Pro Ser Ala His Gly Ser Cys Ala Asp Trp Ala Ala Arg Trp 740 745 750 Tyr Phe Val Ala Ser Val Gly Gln Cys Asn Arg Phe Trp Tyr Gly Gly 755 760 765 Cys His Gly Asn Ala Asn Asn Phe Ala Ser Glu Gln Glu Cys Met Ser 770 775 780 Ser Cys Gln Gly Ser Leu His Gly Pro Arg Arg Pro Gln Pro Gly Ala 785 790 795 800 Ser Gly Arg Ser Thr His Thr Asp Gly Gly Gly Ser Ser Pro

Ala Gly 805 810 815 Glu Gln Glu Pro Ser Gln His Arg Thr Gly Ala Ala Val Gln Arg Lys 820 825 830 Pro Trp Pro Ser Gly Gly Leu Trp Arg Gln Asp Gln Gln Pro Gly Pro 835 840 845 Gly Glu Ala Pro His Thr Gln Ala Phe Gly Glu Trp Pro Trp Gly Gln 850 855 860 Glu Leu Gly Ser Arg Ala Pro Gly Leu Gly Gly Asp Ala Arg Ser Pro 865 870 875 880 Ala Pro Pro Lys Asn Gly Lys Arg His Asp His Ala Ile Leu Leu Thr 885 890 895 Gly Phe Asp Ile Cys Ser Trp Lys Asn Glu Pro Cys Asp Thr Leu Gly 900 905 910 Phe Ala Pro Phe His Ser Ser Ser Tyr Arg Ile Ser Leu Ala Gly Val 915 920 925 Glu Pro Ser Leu Val Gln Ala Ala Leu Gly Gln Leu Val Arg Leu Ser 930 935 940 Cys Ser Asp Asp Thr Ala Pro Glu Ser Gln Ala Ala Trp Gln Lys Asp 945 950 955 960 Gly Gln Pro Ile Ser Ser Asp Arg His Arg Leu Gln Phe Asp Gly Ser 965 970 975 Leu Ile Ile His Pro Leu Gln Ala Glu Asp Ala Gly Thr Tyr Ser Cys 980 985 990 Gly Ser Thr Arg Pro Gly Arg Asp Ser Gln Lys Ile Gln Leu Arg Ile 995 1000 1005 Ile Gly Leu Cys Pro His Pro Ile His His Ser His Leu Val Ser Pro 1010 1015 1020 Gly Leu Met Thr Gly Gly Asp Met Ala Val Leu Ser Glu Ala Glu Leu 1025 1030 1035 1040 Ser Arg Phe Pro Gln Pro Arg Asp Pro Ala Gln Asp Phe Gly Gln Ala 1045 1050 1055 Gly Ala Ala Gly Pro Leu Gly Ala Ile Pro Ser Ser His Pro Gln Pro 1060 1065 1070 Ala Asn Arg Leu Arg Leu Asp Gln Asn Gln Pro Arg Val Val Asp Ala 1075 1080 1085 Ser Pro Gly Gln Arg Ile Arg Met Thr Cys Arg Ala Glu Gly Phe Pro 1090 1095 1100 Pro Pro Ala Ile Glu Trp Gln Arg Asp Gly Gln Pro Val Ser Ser Pro 1105 1110 1115 1120 Arg His Gln Leu Gln Pro Asp Gly Ser Leu Val Ile Ser Arg Val Ala 1125 1130 1135 Val Glu Asp Gly Gly Phe Tyr Thr Cys Val Ala Phe Asn Gly Gln Asp 1140 1145 1150 Arg Asp Gln Arg Trp Val Gln Leu Arg Val Leu Gly Glu Leu Thr Ile 1155 1160 1165 Ser Gly Leu Pro Pro Thr Val Thr Val Pro Glu Gly Asp Thr Ala Arg 1170 1175 1180 Leu Leu Cys Val Val Ala Gly Glu Ser Val Asn Ile Arg Trp Ser Arg 1185 1190 1195 1200 Asn Gly Leu Pro Val Gln Ala Asp Gly His Arg Val His Gln Ser Pro 1205 1210 1215 Asp Gly Thr Leu Leu Ile Tyr Asn Leu Arg Ala Arg Asp Glu Gly Ser 1220 1225 1230 Tyr Thr Cys Ser Ala Tyr Gln Gly Ser Gln Ala Val Ser Arg Ser Thr 1235 1240 1245 Glu Val Lys Val Val Ser Pro Ala Pro Thr Ala Gln Pro Arg Asp Pro 1250 1255 1260 Gly Arg Asp Cys Val Asp Gln Pro Glu Leu Ala Asn Cys Asp Leu Ile 1265 1270 1275 1280 Leu Gln Ala Gln Leu Cys Gly Asn Glu Tyr Tyr Ser Ser Phe Cys Cys 1285 1290 1295 Ala Ser Cys Ser Arg Phe Gln Pro His Ala Gln Pro Ile Trp Gln 1300 1305 1310 92 10 PRT Artificial Sequence Consensus amino acid sequence VARIANT (1)...(1) Xaa at position 1 can be G or S or T or A or L or I or V or N VARIANT (2)...(3) Xaa = any amino acid VARIANT (6)...(6) Xaa at position 6 can be L or I or V or M or F or Y or W VARIANT (7)...(7) Xaa at position 7 can be A, Q, N, L, G, S, V, T, I, M, F, Y, C, or W VARIANT (9)...(9) Xaa = any amino acid VARIANT (10)...(10) Xaa at position 10 can be L, I, V, M, F, Y, W, G, S, P or Q 92 Xaa Xaa Xaa His Glu Xaa Xaa His Xaa Xaa 1 5 10 93 11 PRT Artificial Sequence Consensus amino acid sequence 93 His Glu Leu Gly His Asn Leu Gly Met Lys His 1 5 10

Claims

1-20. (canceled)

21. A method for simultaneous synthesis of multiple copies of different single-stranded circular DNA molecules, comprising: (a) contacting a plurality of universal hairpin oligonucleotides with at least two different target hairpin oligonucleotides, wherein each said hairpin oligonucleotide contains a segment that does not hybridize with any segment of the same or another of said hairpin oligonucleotides and wherein each of said hairpin oligonucleotides comprises a single stranded terminal non-palindromic sequence (segment C) such that said segment C of each universal hairpin oligonucleotide is complementary to the segment C of each target hairpin oligonucleotide but said segment C of any target oligonucleotide is not complementary to segment C of the same or another target hairpin oligonucleotide, and wherein said contacting occurs under conditions promoting said contacting and promoting hybridization of said segments C, (b) ligating the resulting hybridized hairpin oligonucleotides to form a population of monomers each comprising a duplex linear segment with a single-stranded loop at each end.

22. The method of claim 21 further comprising amplifying the monomers via rolling circle amplification.

23. The method of claim 22 wherein said duplex linear segment of step (b) comprises at least one endonuclease restriction site, the method further comprising contacting the product of rolling circle amplification with an endonuclease specific for said endonuclease restriction site to form a new set of hairpin oligonucleotides and then repeating steps (a) through (c) using said new set of hairpin oligonucleotides.

24. The method of claim 21 wherein the target hairpin oligonucleotides of step (a) are of different sizes.

25. The method of claim 21 wherein at least one of the hairpin oligonucleotides contains a pre-selected nucleotide sequence.

26. The method of claim 21 wherein said duplex linear segment of step (b) comprises at least one endonuclease restriction site.

27. The method of claim 26 wherein the endonuclease restriction site contains a phosphorothioate derivative.

28. The process of claim 21 wherein said restriction site is a BamHI restriction site and said endonuclease is Bam HI.

29. The method of claim 21 wherein the ligation step employs an enzyme.

30. The method of claim 29 wherein the enzyme is selected from the group consisting of T4 ligase, Ampligase and E. coli ligase.

31. The method of claim 21 further comprising ligation at a temperature of between 4.degree. C. to 65.degree. C.

32. The method of claim 21 wherein the ligation step is non-enzymatic.

33. The process of claim 32 wherein the ligation step requires the formation of a phosphorothioate derivative of a hairpin oligonucleotide.

34. The method of claim 21 wherein said double-stranded linear segment formed in step (b) comprises at least two endonuclease restriction sites.

35. The method of claim 21 wherein said single-stranded circular DNA molecules are produced in a ratio equal to that of the respective starting target hairpin oligonucleotides used to form said circular DNA molecules.

36. The method of claim 21 wherein at least 3 different target hairpin oligonucleotides are contacted with said universal hairpin oligonucleotides.

37. The method of claim 21 wherein at least 4 different target hairpin oligonucleotides are contacted with said universal hairpin oligonucleotides.

38. A method for simultaneous synthesis of multiple copies of different single-stranded circular DNA molecules, comprising: (a) contacting a plurality of universal hairpin oligonucleotides with at least two different target hairpin oligonucleotides, wherein each said hairpin oligonucleotide contains a segment that does not hybridize with any segment of the same or another of said hairpin oligonucleotides and wherein each of said hairpin oligonucleotides comprises a single stranded terminal non-palindromic sequence (segment C) such that said segment C of each universal hairpin oligonucleotide is complementary to the segment C of each target hairpin oligonucleotide but said segment C of any target oligonucleotide is not complementary to segment C of the same or another target hairpin oligonucleotide, and wherein said contacting occurs under conditions promoting said contacting and promoting hybridization of said segments C, (b) ligating the resulting hybridized hairpin oligonucleotides to form a population of monomers each comprising a duplex linear segment with a single-stranded loop at each end, (c) contacting said monomers with a plurality of deoxynucleoside triphosphates (dNTPs), multiple primer oligonucleotides comprising at least one oligonucleotide complementary to at least one segment of each of the monomers and a DNA polymerase capable of supporting rolling circle amplification (RCA), said contacting occurring under conditions promoting said contacting and promoting said rolling circle amplification to form an RCA product, thereby simultaneously generating multiple copies of different single-stranded circular DNA molecules.