COMPOSITION FOR THE DIAGNOSIS, PREVENTION OR TREATMENT OF DISEASES RELATED TO CELLS EXPRESSING IL-8 OR GRO-ALPHA, COMPRISING UCB-MSCs

Chang; Jong Wook ;   et al.

Patent Application Summary

U.S. patent application number 13/680995 was filed with the patent office on 2013-07-25 for composition for the diagnosis, prevention or treatment of diseases related to cells expressing il-8 or gro-alpha, comprising ucb-mscs. This patent application is currently assigned to Medipost Co., Ltd.. The applicant listed for this patent is Medipost Co., Ltd.. Invention is credited to Jong Wook Chang, Dal Soo Kim, Won II Oh, Yoon-Sun Yang.

Application Number20130189189 13/680995
Document ID /
Family ID40388015
Filed Date2013-07-25

United States Patent Application 20130189189
Kind Code A1
Chang; Jong Wook ;   et al. July 25, 2013

COMPOSITION FOR THE DIAGNOSIS, PREVENTION OR TREATMENT OF DISEASES RELATED TO CELLS EXPRESSING IL-8 OR GRO-ALPHA, COMPRISING UCB-MSCs

Abstract

Provided is a gene therapy composition for transferring one of a therapeutical gene, a maker gene, or a mixture thereof to a cell that expresses interleukin-8(IL-8) or GRO-.alpha. and induces tropism of mesenchymal stem cells isolated from umbilical cord blood and/or the mesenchymal stem cells expanded from said mesenchymal stem cells (UCB-MSCs), wherein the cell-treating composition includes UCB-MSCs. Provided is a composition for treating disease related to a cell expressing IL-8 or GRO-.alpha., that is, a brain tumor in gene therapy, by using UCB-MSCs. Provided is a composition or kit for diagnosing brain tumors, preventing brain tumors, treating brain tumors, or monitoring brain tumor treatment progression by using UCB-MSCs.


Inventors: Chang; Jong Wook; (Seoul, KR) ; Kim; Dal Soo; (Seoul, KR) ; Yang; Yoon-Sun; (Seoul, KR) ; Oh; Won II; (Seoul, KR)
Applicant:
Name City State Country Type

Medipost Co., Ltd.;

Seoul

KR
Assignee: Medipost Co., Ltd.
Seoul
KR

Family ID: 40388015
Appl. No.: 13/680995
Filed: November 19, 2012

Related U.S. Patent Documents

Application Number Filing Date Patent Number
12633622 Dec 8, 2009
13680995
PCT/KR2008/005026 Aug 27, 2008
12633622
61089733 Aug 18, 2008
60972966 Sep 17, 2007

Current U.S. Class: 424/9.34 ; 424/9.1; 424/9.6; 424/93.21
Current CPC Class: A61K 35/44 20130101; A61K 48/00 20130101; A61K 49/08 20130101; A61K 49/0002 20130101; A61K 49/0017 20130101; A61P 35/00 20180101
Class at Publication: 424/9.34 ; 424/93.21; 424/9.1; 424/9.6
International Class: A61K 49/08 20060101 A61K049/08; A61K 49/00 20060101 A61K049/00; A61K 48/00 20060101 A61K048/00

Foreign Application Data

Date Code Application Number
Aug 29, 2007 KR 1020070087228
Jul 10, 2008 KR 1020080067247

Claims



1. A method of preventing or treating a tumor comprising administering to a subject an effective dose of a composition comprising mesenchymal stem cells derived from umbilical cord blood (UCB-MSC).

2. The method of claim 1, wherein a cell of the tumor expresses at least one gene selected from a group of a gene encoding IL-8 and a gene encoding GRO-.alpha..

3. The method of claim 1, wherein the tumor is selected from the group consisting of a brain tumor, a liver hepatoma, a breast cancer, a colon cancer and a B-cell neoplasm.

4. The method of claim 1, wherein an anti-tumor agent gene is introduced into the UCB-MSC.

5. The method of claim 4, wherein the anti-tumor agent gene is selected from the group consisting of a tumor suppressor gene, an apoptosis-inducing factor gene, a cell cycle regulatory factor gene and an angiogenesis inhibitor gene.

6. The method of claim 5, wherein the tumor suppressor gene is selected from the group consisting of a gene encoding phosphatase and tensin homolog (PTEN), a gene encoding Maspin, a gene encoding RUNX3, a gene encoding Caveolin-1, a gene encoding nm23, a gene encoding Rb protein, a gene encoding Brush-1, a gene encoding inhibitor of tumor growth (ING-4), a gene encoding survivin, a gene encoding X chromosome linked inhibitor apoptosis protein (XIAP), a gene encoding neural apoptosis inhibitory protein (NAIP) and genes encoding proteins related to regulation of said genes.

7. The method of claim 5, wherein the apoptosis inducing factor gene is selected from the group consisting of a gene encoding cytokine, a gene encoding interleukin, a gene encoding a tumor necrosis factor (TNF), a gene encoding interferon (INF-.alpha., INF-.beta., INF-.gamma.), a gene encoding a colony stimulating factor (CSFs), a gene encoding p53, a gene encoding Apaf-1, a gene encoding TRAIL, a gene encoding Caspase, a gene encoding Bax, a gene encoding Bad, a gene encoding FADD, a gene encoding JNK, a gene encoding p38 kinase and genes encoding proteins related to regulation of said genes.

8. The method of claim 7, wherein the cell cycle regulatory factor gene is selected from the group consisting of a gene encoding cdc2, a gene encoding Cyclin (Cyclin A, Cyclin D, Cyclin E), a gene encoding cdc25C, a gene encoding WAF, a gene encoding INK4, a gene encoding CDK (CDK1, CDK2, CDK4, CDK6), a gene encoding Rb protein, a gene encoding E2F, an antisense or siRNA thereof and genes encoding proteins related to the regulation of said genes.

9. The method of claim 5, wherein the angiogenesis inhibitor gene is selected from the group consisting of a gene encoding thrombospondin-1, a gene encoding endostatin, a gene encoding tumstatin, a gene encoding canstatin, a gene encoding vastatin, a gene encoding restin, a gene encoding a vascular endothelial growth factor inhibitor, a gene encoding maspin, a gene encoding angiopoietins, a gene encoding 16-kd prolactin fragment and a gene encoding endorepellin.

10. The method of claim 1, wherein a prodrug converting enzyme gene is introduced to the UCB-MSC.

11. The method of claim 10, wherein the method further comprises administering a prodrug of an anticancer drug.

12. The method of claim 10, wherein the prodrug converting enzyme gene is selected from cytosine deaminase gene and CYP2B 1 gene.

13. The method of claim 1, wherein an antisense or siRNA of a gene related to brain tumor is introduced to the UCB-MSC.

14. The method of claim 13, wherein the gene related to brain tumor is selected from the group consisting of a gene encoding a Ras family protein, a gene encoding c-myc, a gene encoding abl, a gene encoding erbB-1, a gene encoding EGFR, a gene encoding Bax, a gene encoding Apaf-1 interacting protein (APIP), a gene encoding Wnt-1-induced secreted protein 1 (WISP-1), a gene encoding Wnt, a gene encoding Raf-1, a gene encoding Src, a gene encoding Akt, a gene encoding Erk-1, 2 and a gene encoding BcL-2.

15. The method of claim 1, wherein an oncolytic virus is introduced to the UCB-MSC.

16. The method of claim 15, wherein the oncolytic virus is selected from Herpes simplex virus and Reovirus type 3.

17. The method of claim 3, wherein the brain tumor is selected from the group consisting of astrocytoma, pilocytic astrocytoma, low-grade astrocytoma, anaplastic astrocytoma, glioblastoma multiforme, brain stem cell glioma, ependymoma, subependymoma, ganglioneuroma, mixed glioma, oligodendroglioma, optic nerve glioma, acoustic neuroma, chordoma, CNS lymphoma, craniopharyngioma, hemangioblastoma, medulloblastoma, meningioma, pineal tumors, pituitary tumors, primitive neuroectodermal tumors, rhabdoid tumors, schwannoma, cysts, neurofibromatosis, pseudotumor cerebri and tuberous sclerosis.

18. The method of claim 1, further comprises enhancing the expression level of at least one gene selected from the group consisting of a gene encoding IL-8 receptor and a gene encoding GRO-.alpha. receptor at the USC-MSC.

19. The method of claim 18, wherein the IL-8 receptor is selected from a group consisting of CXCR1 and CXCR2.

20. The method of claim 18, wherein the GRO-.alpha. receptor CXCR2.

21. The method of claim 18, wherein the enhancement of the expression is achieved by at least one selected from the group consisting of activating the endogenous gene and introducing an exogenous gene.

22. A kit for identifying the location and the size of a brain tumor, comprising UCB-MSC, said UCB-MSC being labeled with a detectable marker.

23. The kit of claim 22, wherein the detectable marker is selected from luciferase-containing enzyme-based fluorescent detector and Tat peptide-derivatized magnetic nanoparticles.

24. A method of identifying the location and the size of a brain tumor of a subject, wherein the method comprises: (a) administering to the subject UCB-MSC; (b) identifying the location and the size of the distribution of the administered UCB-MSC.

25. The method of claim 24, wherein the UCB-MSC are labeled with a detectable marker.

26. The method of claim 24, wherein the detectable marker is selected from luciferase-containing enzyme-based fluorescent detector and Tat peptide-derivatized magnetic nanoparticles.

27. A method of monitoring a progression of a tumor treatment in a subject who is received the brain tumor treatment, wherein the method comprises: (a) first administering to the subject UCB-MSC; (b) identifying the location and the size of the distribution of the first administered UCB-MSC in the subject; (c) second administering to the subject UCB-MSC; (d) identifying the location and the size of the distribution of the second administered UCB-MSC in the subject; (e) comparing the location and the size of the distribution identified by (b) and (d), wherein the subject receives a treatment of the tumor during the period starting from the first administration of the UCB-MSC to the second administration of the UCB-MSC.

28. The method of claim 27, wherein the UCB-MSC are labeled with a detectable marker.

29. The method of claim 28, wherein the detectable marker is selected from luciferase-containing enzyme-based fluorescent detector and Tat peptide-derivatized magnetic nanoparticles.

30. A method for delivering a therapeutic gene to a site of a subject, the site comprising cells expressing at least one selected from the group consisting of IL-8 and GRO-.alpha. and inducing tropism of UCB-MSC toward the cells, wherein the method comprises the step of administering to the subject an effective dose of the UCB-MSC.

31. The method of claim 30, wherein the therapeutic gene is introduced into the UCB-MSC.

32. The method of claim 30, wherein the therapeutic gene is selected from the group consisting of a tumor suppressor gene, an apoptosis-inducing factor gene, a cell cycle regulatory gene and an angiogenesis inhibitor gene.

33. The method of claim 32, wherein the tumor suppressor gene is selected from the group consisting of a gene encoding phosphatase and tensin homolog (PTEN), a gene encoding Maspin, a gene encoding RUNX3, a gene encoding Caveolin-1, a gene encoding nm23, a gene encoding Rb protein, a gene encoding Brush-1, a gene encoding inhibitor of tumor growth (ING-4), a gene encoding survivin, a gene encoding X chromosome linked inhibitor apoptosis protein (XIAP), a gene encoding neural apoptosis inhibitory protein (NAIP), and genes encoding proteins related to the regulation of said genes.

34. The method of claim 32, wherein the apoptosis-inducing factor gene is selected from the group consisting of a gene encoding cytokine, a gene encoding interleukin, a gene encoding a tumor necrosis factor (TNF), a gene encoding interferon (INF-.alpha., INF-.beta., INF-.gamma.), a gene encoding a colony stimulating factor (CSFs), a gene encoding p53, a gene encoding Apaf-1, a gene encoding TRAIL, a gene encoding Caspase, a gene encoding Bax, a gene encoding Bad, a gene encoding FADD, a gene encoding JNK, a gene encoding p38 kinase, and genes encoding proteins related to the regulation of said genes.

35. The method of claim 32, wherein the cell cycle regulatory factor gene is selected from the group consisting of a gene encoding cdc2, a gene encoding Cyclin Cyclin A, Cyclin D, Cyclin E), a gene encoding cdc25C, a gene encoding WAF, a gene encoding INK4, a gene encoding CDK (CDK1, CDK2, CDK4, CDK6), a gene encoding Rb protein, a gene encoding E2F, an antisense or SiRNA thereof, and genes encoding proteins related to the regulation of said genes.

36. The method of claim 32, wherein the angiogenesis inhibitor gene is selected from the group consisting of a gene encoding thrombospondin-1, a gene encoding endostatin, a gene encoding tumstatin, a gene encoding canstatin, a gene encoding vastatin, a gene encoding restin, a gene encoding a vascular endothelial growth factor inhibitor, a gene encoding maspin, a gene encoding angiopoietins, a gene encoding 16-kd prolactin fragment and a gene encoding endorepellin.

37. The method of claim 30, wherein a prodrug converting enzyme gene is introduced to the UCB-MSC.

38. The method of claim 30, wherein the method further comprises administering a prodrug of an anticancer drug.

39. The method of claim 37, wherein the prodrug converting enzyme gene is selected from the group consisting of cytosine deaminase gene and a CYP2B 1 gene.

40. The method of claim 30, wherein an antisense or siRNA of a gene related to tumor is introduced to the UCB-MSC.

41. The method of claim 40, wherein the gene related to tumor is selected from the group consisting of a gene encoding Ras family protein, a gene encoding c-myc, a gene encoding abl, a gene encoding erbB-1, a gene encoding EGF-R, a gene encoding Bax, a gene encoding an Apaf-1 interacting protein (APIP), a gene encoding Wnt-1-induced secreted protein 1 (WISP-1), a gene encoding Wnt, a gene encoding Raf-1, a gene encoding Src, a gene encoding Akt, a gene encoding Erk-1,2 and a gene encoding BcL-2.

42. The method of claim 30, wherein an oncolytic virus is introduced to the UCB-MSC.

43. The method of claim 42, wherein the oncolytic virus is selected from the group consisting of Herpes simplex virus and Reovirus type 3.

44. The method of claim 30, wherein the cell expressing at least one selected from the group consisting of IL-8 and GRO-.alpha. is selected from the group consisting of a brain tumor cell, a hepatoma cell, a breast cancer cell, a lung cell with an acute respiratory distress syndrome, a colon cancer cell and a B-cell neoplasm cell.

45. The method of claim 44, wherein the B-cell neoplasm cell is selected from the group consisting of a common B acute lymphoblastic leukemia cell, a precursor B acute lymphoblastic leukemia cell, a B-cell chronic lymphocytic leukemia cell, a mantle cell lymphoma cell, a Burkitt's lymphoma cell and a Follicular lymphoma cell.

46. A kit for identifying the location and the size of a site of a subject, the site comprising cells expressing at least one selected from the group consisting of IL-8 and GRO-.alpha. and inducing tropism of UCB-MSC toward the cells, wherein the kit comprises UCB-MSC, the UCB-MSC are labeled with a detectable marker.

47. The kit of claim 46, wherein the detectable marker is selected from luciferase-containing enzyme-based fluorescent detector and Tat peptide-derivatized magnetic nanoparticles.

48. The kit of claim 46, wherein the cell expressing at least one selected from the group consisting of IL-8 and GRO-.alpha. is selected from the group consisting of a brain tumor cell, a hepatoma cell, a breast cancer cell, a lung cell with an acute respiratory distress syndrome, a colon cancer cell and a B-cell neoplasm cell.

49. The kit of claim 48, wherein the B-cell neoplasm cell is selected from the group consisting of a common B acute lymphoblastic leukemia cell, a precursor B acute lymphoblastic leukemia cell, a B-cell chronic lymphocytic leukemia cell, a mantle cell lymphoma cell, a Burkitt's lymphoma cell and a Follicular lymphoma cell.

50. A method of identifying the location and the size of a site of a subject, the site comprising cells expressing at least one selected from the group consisting of IL-8 and GRO-.alpha. and inducing tropism of UCB-MSC toward the cells, wherein the method comprises: (a) administering to the subject UCB-MSC; (b) identifying the location and the size of the distribution of the administered UCB-MSC.

51. The method of claim 50, wherein the UCB-MSC are labeled with a detectable marker.

52. The method of claim 51, wherein the detectable marker is selected from luciferase-containing enzyme-based fluorescent detector and Tat peptide-derivatized magnetic nanoparticles.

53. The method of claim 50, wherein the cell expressing at least one selected from the group consisting of IL-8 and GRO-.alpha. is selected from the group consisting of a brain tumor cell, a hepatoma cell, a breast cancer cell, a lung cell with an acute respiratory distress syndrome, a colon cancer cell and a B-cell neoplasm cell.

54. The method of claim 53, wherein the B-cell neoplasm cell is selected from the group consisting of a common B acute lymphoblastic leukemia cell, a precursor B acute lymphoblastic leukemia cell, a B-cell chronic lymphocytic leukemia cell, a mantle cell lymphoma cell, a Burkitt's lymphoma cell and a Follicular lymphoma cell.

55. A method of monitoring treatment progression of a disease occurred in a site of a subject, the site comprising cells expressing at least one selected from groups consisting of IL-8 and GRO-.alpha. and inducing tropism of UCB-MSC, wherein the method comprises: (a) first administering to the subject UCB-MSC; (b) identifying the location and the size of the distribution of the first administered UCB-MSC in the subject; (a) second administering to the subject UCB-MSC; (b) identifying the location and the size of the distribution of the second administered UCB-MSC in the subject; and (c) comparing the location and the size of the distribution identified by (b) and (d), wherein the subject receives a treatment of the tumor during the period starting from the first administration of the UCB-MSC to the second administration of the UCB-MSC.

56. The method of claim 55, wherein the UCB-MSC are labelled with a detectable marker.

57. The method of claim 56, wherein the detectable marker is selected from luciferase-containing enzyme-based fluorescent detector and Tat peptide-derivatized magnetic nanoparticles.

58. The method of claim 55, wherein the cell expressing at least one selected from the group consisting of IL-8 and GRO-.alpha. is selected from the group consisting of a brain tumor cell, a hepatoma cell, a breast cancer cell, a lung cell with an acute respiratory distress syndrome, a colon cancer cell and a B-cell neoplasm cell.

59. The method of claim 56, wherein the B-cell neoplasm cell is selected from the group consisting of a common B acute lymphoblastic leukemia cell, a precursor B acute lymphoblastic leukemia cell, a B-cell chronic lymphocytic leukemia cell, a mantle cell lymphoma cell, a Burkitt's lymphoma cell and a Follicular lymphoma cell.

60. A method of delivering an anti-tumor agent to a site of a tumor in a subject, which comprises administering mesenchymal stem cells together with the anti-tumor agent to the site, wherein the mesenchymal stem cells (MSCs) are umbilical cord blood-derived MSCs ("UCB-MSC").

61. The method according to claim 60, wherein the MSCs are used in an amount of 1.times.10.sup.4-1.times.10.sup.7 cells/kg body weight.

62. The method according to claim 60, wherein the anti-tumor agent is selected from the group consisting of a tumor suppressor gene, an apoptosis-inducing factor gene, a cell cycle regulatory factor gene and an angiogenesis inhibitor gene.

63. The method according to claim 60, wherein the anti-tumor agent is admixed with the UCB-MSCs.

64. The method according to claim 60, wherein the anti-tumor agent is carried within the UCB-MSCs.

65. The method according to claim 60, wherein the tumor is a brain tumor.

66. The method according to claim 62, wherein the tumor suppressor gene is selected from the group consisting of phosphatase and tensin homolog gene (PTEN), Maspin gene, RUNX3 gene, Caveolin-1 gene, nm23 gene, Rb protein gene, Brush-1 gene, a gene encoding an inhibitor of tumor growth (ING-4), surviving gene, X chromosome linked inhibitor apoptosis protein (XIAP) gene, neural apoptosis inhibitory protein (NAIP) gene and genes encoding a protein related to regulating said genes.

67. The method according to claim 62, wherein the apoptosis inducing factor gene is selected from the group consisting of a gene encoding cytokine, a gene encoding interleukin, a gene encoding a tumor necrosis factor (TNF), a gene encoding interferon (INF-.alpha., INF-.beta., INF-.gamma.), a gene encoding a colony stimulating factor (CSFs), a gene encoding p53, a gene encoding Apaf-1, a gene encoding TRAIL, a gene encoding Caspase, a gene encoding Bax, a gene encoding Bad, a gene encoding FADD, a gene encoding JNK, a gene encoding p38 kinase and genes encoding proteins related to regulating said genes.

68. The method according to claim 62, wherein the cell cycle regulatory factor gene is selected from the group consisting of a gene encoding cdc2, a gene encoding Cyclin (Cyclin A, Cyclin D, Cyclin E), a gene encoding cdc25C, a gene encoding WAF, a gene encoding INK4, a gene encoding CDK (CDK1, CDK2, CDK4, CDK6), a gene encoding Rb protein, a gene encoding E2F, an antisense or siRNA thereof and genes encoding proteins related to regulating said genes.

69. The method according to claim 62, wherein the angiogenesis inhibitor gene is selected from the group consisting of a gene encoding thrombospondin-1, a gene encoding endostatin, a gene encoding tumstatin, a gene encoding canstatin, a gene encoding vastatin, a gene encoding restin, a gene encoding a vascular endothelial growth factor inhibitor, a gene encoding maspin, a gene encoding angiopoietins, a gene encoding 16-kd prolactin fragment and a gene encoding endorepellin.

70. The method according to claim 60, wherein the anti-tumor agent is a prodrug converting enzyme gene.

71. The method according to claim 60, wherein the anti-tumor agent is an antisense or siRNA of a gene related to a brain tumor.

72. The method according to claim 71, wherein the gene related to brain tumor is selected from the group consisting of a gene encoding Ras family, a gene encoding c-myc, a gene encoding abl, a gene encoding erbB-1, a gene encoding EGF-R, a gene encoding Bax, a gene encoding Apaf-1 interacting protein (APIP), a gene encoding Wnt-1-induced secreted protein 1 (WISP-1), a gene encoding Wnt, a gene encoding Raf-1, a gene encoding Src, a gene encoding Akt, a gene encoding Erk-1,2 and a gene encoding BcL-2.

73. The method according to claim 60, wherein the anti-tumor agent is an oncolytic virus.

74. The method according to claim 73, wherein the oncolytic virus is selected from Herpes simplex virus and Reovirus type 3.

75. The method according to claim 74, wherein the brain tumor is selected from the group consisting of astrocytoma, pilocytic astrocytoma, low-grade astrocytoma, anaplastic astrocytoma, glioblastoma multiforme, brain stem glioma, ependymoma, subependymoma, ganglioneuroma, mixed glioma, oligodendroglioma, optic nerve glioma, acoustic neuroma, chordoma, CNS lymphoma, craniopharyngioma, hemangioblastoma, medulloblastoma, meningioma, pineal tumors, pituitary tumors, primitive neuroectodermal tumors, rhabdoid tumors, schwannoma, cysts, neurofibromatosis, pseudotumor cerebri and tuberous sclerosis.
Description



TECHNICAL FIELD

[0001] The present invention relates to a gene therapy composition for transferring a therapeutical gene, a marker gene, or a product thereof to a cell that expresses interleukin-8(IL-8) or GRO-.alpha. and induces tropism of umbilical cord blood-derived mesenchymal stem cells or mesenchymal stem cells isolated from umbilical cord blood and/or the mesenchymal stem cells expanded from said mesenchymal stem cells (UCB-MSCs), wherein the gene therapy composition includes UCB-MSCs.

[0002] The present invention also relates to preventing or treating disease related to a cell expressing IL-8 or GRO-.alpha., or brain tumors in gene therapy, using the composition includes UCB-MSCs.

[0003] The present invention also relates to a composition or kit for diagnosing brain tumors, preventing brain tumors, treating brain tumors, or monitoring brain tumor treatment progression, using UCB-MSCs.

BACKGROUND ART

[0004] It is known that stem cells migrate toward sites of pathology. Recently, it was found that bone marrow-derived mesenchymal stem cells (BM-MSCs) have a tropism for tumors and migrate toward tumor sites. Such BM-MSCs that can migrate to sites of specific tumors may prove to be a useful tool in gene therapy. For example, BM-MSCs having a tropism for tumors can be used as vehicles for transferring a therapeutic suicide gene to tumor sites [see Ponte A. L. et al., Stem Cells, 25, 1737-1745 (2005); Kahler C. M. et al., Respir Res 8, 50 (2007)]. Despite this interesting phenomenon, the molecular mechanisms regulating MSCs trafficking to tumor are unclear.

[0005] Growing evidence over several years indicates that induction of BM-MSCs migration seems to be stimulated by several soluble factors. Recently, monocyte chemoattractant protein-1 (MCP-1) secreted from breast cancer cells has been shown to stimulate BM-MSCs migration [see Dwyer R. M. et al. Clin Cancer Res 13, 5020-5027 (2007)]. Furthermore, chemokine ligand2 (CCL2) and chemokine ligand10 (CCL-10) can induce the migration of neural progenitor cells to sites damaged within the middle

cerebral artery occlusion (MCAo) stroke model [see J Neurosci Res 85, 2120-2125 (2007)]. An insulin-like growth factor-1 (IGF-1) markedly increased the rat BM-MSCs migratory response [see Li Y. et al. Biochem Biophys Res Commun 356, 780-784 (2007)]. Therefore, identifying the soluble factors that affect migration events of MSCs is important for understanding-how MSCs migrate toward tumors or damaged tissues.

[0006] Genes introduced to BM-MSCs are over-expressed in vivo and show bioactivity. For example, BM-MSCs to which a human hAng1 gene is introduced stimulate generation of blood to vessels in an infarction site of an acute myocardial infarction model animal [see Sun L. et al., Biochemical Biophysical Research Communication 357 (2007) 779-784], BM-MSCs overexpressing Akt surprisingly treat myocardial infarction and improve functions of heart [see Nicolas N. et al., Molecular Therapy 14(6), 840-850, 2006], Bcl-2 gene-modified BM-MSCs prevent apoptosis and improve functions of heart [see Stem Cells 25, 2118-2127 (2007)], and BM-MSCs overexpressing endothelial nitric oxide synthase recovers the damage of right ventricular caused by pulmonary hypertension [see Sachiko et al., Circulation, 114[suppl I]:I-181.about.I-185]. These results indicate that MSCs to which genes are introduced can be used as a tool in gene therapy.

[0007] Meanwhile, in general, cells of the central nervous system are well regulated, wherein the central nervous system consists of a brain and a spinal cord. However, when this regulation collapses, cells are continuously divided and tumors are formed. Tumors can be categorized as benign tumors or malignant tumors. The central nervous system has neurons, and glia cells that support and protect the neurons. Tumors generated in glia cells are known as glioma. Glioma accounts for 50% of primary brain tumors and accounts for 15% of primary spinal cord tumors. In addition, brain tumors include neural tumors, blood vessel tumors, and gland tumors. There is also a secondary brain tumor caused by other tumors developed in other sites of the body. The secondary brain tumor is the most common type of brain tumor.

[0008] Treating brain tumors are difficult due to the sites of the tumors. Brain tumors can be treated by physical surgery or chemotherapy. For physical surgery, when tumor sites are completely removed, complications are likely to occur. For chemotherapy, a high-concentration anticancer drug needs to be injected due to a brain-blood barrier, and thus, it seriously damages other organs. Recently, gene therapy has been used to treat brain tumors. In gene therapy, a gene is introduced for suppressing growth of cancer cells by using a virus vector. Since the virus vector does not have a selective migration capability toward a target cancer site, the virus vector is surface-modified to obtain such capability. However, there is a limit to migrate a sufficient amount of virus vectors to the target cancer site.

[0009] Research results on a homing effect, which is a phenomenon in which stem cells migrate toward a disease site, have been disclosed, indicating that stem cells can be useful delivery media for treating brain tumors. However, mechanisms regulating stem cells trafficking to tumors are unclear. It is known that neural stem cells have a tropism for a type of brain tumor, that is, malignant glioma. Based on this theory, research into a method of transferring genes to a brain tumor site by using neural stem cells that function as a vehicle is being conducted (see Yip S et al., The Cancer J 9(3), 189-204, 2003; Kim S K et al., Clin Cancer Res 12(18), 5550-5556, 2006). Yip et al. found that brain tumors can be treated with neural stem cells carrying an immune regulatory gene, an apoptosis promoting gene, a pro-drug converting enzyme, an oncolytic virus, etc. Brown et al. identified that brain tumors can be effectively treated by injecting a cytosine deaminase gene-containing vector into the brain, wherein the cytosine deaminase gene changes 5-fluorocytosine (5-FC) into 5-fluorouracil (5-FU), wherein 5-FU is an anticancer drug and 5-FC is a prodrug of 5-FU (see Brown A B et al., Human Gene Ther. 14(18), 1777-1785, 2003). Ehtesham et al. reported that growth of brain tumors was decreased by injecting neural stem cells treated for delivering interleukin-12 or a tumor necrosis factor-related apoptosis-inducing ligand (Cancer Res 62, 5657-5663, 2002; Cancer Res 62, 7170-7174, 2002). However, using neural stem cell in clinical experiments causes ethical problems related to how neural stem cells are taken, and immunological rejection caused by allogenic transplantation. Accordingly, there is a need to find other types of stem cells that do not cause these problems and can be easily obtained.

[0010] Akira et al. disclosed that BM-MSCs have a tropism for brain tumors (see Cancer Res 65(8), 3307-3316, 2005). BM-MSCs can be taken from patients. When BM-MSCs are injected through autologous transplantation, immunological rejection does not occur, which is an advantage for a clinical use. In a study, human BM-MSCs were injected into nude mice having skulls transplanted with human glioma cell lines through a carotid artery. As a result, the human BM-MSCs were found only in glioma and not in a normal part of the brain adjacent to glioma. In addition, even when human BM-MSCs were transplanted into a skull, human BM-MSCs migrated toward glioma. When human BM-MSCs were infected with an adenovirus vector containing cDNA of an IFN-beta gene and then the resultant vector was injected into a glioma-transplanted skull of a nude mouse through a carotid artery, the lifetime of the nude mouse was increased. WO07/037,653A1 discloses a composition for treating cancer, comprising BM-MSCs expressing a cytosine deaminase gene. In this case, however, since BM-MSCs are taken through a plurality of complex processes, subjects from which the BM-MSCs are taken suffer from mental and physical stress for a long period of time. Accordingly, there is a need to find other types of stem cells.

[0011] Unlike bone marrow, umbilical cord blood (UCB) having many MSCs can be easily taken from umbilical cords which were discarded in delivery processes. Also, the UCB storage industry is well established and thus, it is easy to find donors. Even when MSCs taken from other human-induced UCB are used, immunological rejection does not occur after transplantation. Accordingly, high immunological stability can be obtained. Therefore, it is very important to identify whether a disease such as a brain tumor can be treated based on tropisom of UCB MSCs. However, such attempts for identifying availability of UCB-MSCs have not yet been made. All the references cited in the present specification are incorporated by reference in their entity. Also, all the information disclosed in the present specification is used only to help understanding of the background of the present inventive concept and cannot be prior art.

DETAILED DESCRIPTION OF THE INVENTION

Technical Problem

[0012] Target gene therapy recently developed uses specific migration characteristics of mesenchymal stem cells (MSCs), in which therapeutical genes are introduced to MSCs and then the resultant MSCs are migrated to a disease site and the disease is treated. To develop gene therapy using tropism of MSCs, a molecular mechanism regulating the migration of MSCs toward disease site, for example tumors should be completely understood. However, the molecular mechanism has not yet been determined. Accordingly, the present inventive concept is to find out the molecular mechanism of UCB-MSCs migrating toward a disease site cell, for example, tumor cell and uses the molecular mechanism in gene therapy.

[0013] Although research into whether a disease condition, for example, tumor, including brain tumors can be treated with neural stem cells or bone marrow-derived mesenchymal stem cells (BM-MSCs) are being conducted, collecting neural stem cells and BM-MSCs may lead to ethical problems, immunological rejection, and mental and physical stress of a subject from which BM-MSCs are taken. Accordingly, the present inventive concept also provides a stem cell that can be taken without these problems described above and have better tropism for disease site for example, tumors such as brain tumors.

Technical Solution

[0014] The inventors of the present invention have conducted research in order to solve these problems, and found that mesenchymal stem cells isolated from umbilical cord blood and/or the mesenchymal stem cells expanded from said mesenchymal stem cells (UCB-MSCs) have a tropism for a cell expressing at least one selected from the group consisting of IL-8 and GRO-.alpha., for example a tumor cell such as brain tumor cells and that UCB-MSCs have a stronger migration capability than mesenchymal stem cells isolated from bone marrow and/or the mesenchymal stem cells expanded from said mesenchymal stem cells (BM-MSCs). The inventors have provided a therapeutical application for treating a disease condition, for example a tumor cell such as brain tumor using UCB-MSCs.

[0015] Also, the inventors of the present invention found the tropism of UCB-MSCs is affected by interleukin-8 (IL-8) or GRO-.alpha.. Based on this finding, the inventors of the present invention provide a method of delivering a therapeutical gene or a product thereof to a cell that expresses IL-8 or GRO-.alpha. and induces the tropism of UCB-MSCs, and a therapeutical application thereof.

Advantageous Effects

[0016] Umbilical cord blood derived mesenchymal stem cells (UCB-MSCs) in the composition according to the present invention has a selective tropism for cells that express IL-8 or GRO-.alpha. and thus induce the tropism of UCB-MSCs or brain tumor cells. The tropism capability of the UCB-MSCs is better than that of other stem cells and thus, therapeutical genes or a product thereof can be more effectively delivered than when other conventional stem cells are used. Accordingly, a pharmaceutical composition or a kit comprising UCB-MSCs according to the present invention can be used to diagnose, prevent, and treat diseases related to cells expressing interleukin (IL)-8 or GRO-.alpha. or brain tumors.

MODE OF INVENTIONS

[0017] The inventors of the present invention have studied stem cells having an effective tropism for tumors, and surprisingly found that umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) have a strong tropism for brain tumors, specifically a stronger tropism for brain tumors than bone marrow-derived mesenchymal stem cells (BM-MSCs), which has never been known before. Also, the inventors found that at least one selected from the group consisting of interleukin (IL)-8 and GRO-.alpha. relates to the tropism of UCB-MSCs.

[0018] The inventors co-cultured UCB-MSCs and representative tumor cell lines to identify characteristics of the tropism of UCB-MSCs and cytokine related to those tumor cell lines. Specifically, UCB-MSCs, and one selected from human brain tumor cell lines, such as U-87 MG, LN18, U138, or U251 cells; human rectal cancer cell line such as LS-174T; human B lymphocyte such as NC37; mouse's fibroblast (NIH3T3); a gastric cancer cell line such as KATO III; a lung cancer cell line such as A549, and a liver cancer cell line such as PLC/PRF5 were co-cultured in a transwell chamber to measure mobility of UCB-MSCs. As a result, it was found that UCB-MSCs have a strong tropism for U-87 MG, LN18, U138, and U251 cells which are brain tumor cells (see FIGS. 3 and 4). UCB-MSCs also had tropism for a conditioned media that did not include U-87 MG cells and was obtained by culturing U-87 MG (see FIG. 4).

[0019] Also, the tropism for a brain tumor cell line of UCB-MSCs was compared with that of BM-MSCs that is currently used as a source of stem cells. As a result, it was found that UCB-MSCs have a stronger tropism for a brain tumor cell line than BM-MSCs (FIG. 5). Also, the chemotactic index of UCB-MSCs was largest with respect to the brain tumor cell line among various cancer cell lines (FIG. 6). Such a high chemotactic index with respect to the brain tumor cell is an additional advantage of UCB-MSCs, in addition to the fact that UCB-MSCs can be obtained more easily and have more immunological stability than BM-MSCs, proving that UCB-MSCs are a very suitable medium for gene therapy of a brain tumor because a therapeutical gene can be efficiently transferred to the inside or neighboring portions of the brain tumor.

[0020] The tropism of UCB-MSCs in the transwell chamber may be derived by cytokines that are derived to be secreted in the co-culture of two cells. Thus, two cells were co-cultured in a transwell chamber to prepare a medium and then, the medium was analyzed using the cytokine array. As a result, it was identified that high levels of cytokines, such as IL-8 or GRO-.alpha., were secreted in a medium in which UCB-MSCs and U87 MG had been co-cultured (see FIG. 7). Accordingly, it is highly likely that these cytokines may derive a tropism of the UCB-MSCs.

[0021] The inventors of the present invention cultured UCB-MSCs alone, cultured U-87 MG alone, and co-cultured UCB-MSCs and U-87 MG, and then analyzed IL-8 mRNA levels of these cells using RT-PCR. As a result, UCB-MSCs did not express IL-8 in either the presence or absence of U-87 MG cells. However, U-87 MG expressed IL-8 constitutively in both the presence and absence of UCB-MSCs (see FIG. 8). Treatment of UCB-MSCs with IL-8 significantly enhanced its migration when compared to untreated cells (see (A) of FIG. 9). However, when UCB-MSCs were pre-incubated with anti-CXCR1 antibodies that are antibodies with respect to an IL-8 receptor and recombinant IL-8 was applied to UCB-MSCs, IL-8 mediated migration of UCB-MSCs were reduced in a dose-dependent manner by anti-CXCR1 treatment ((B) of FIG. 9). Anti-CXCR2 treatment also showed the same effect. Similarly, GRO-.alpha. treatment also enhanced UCB-MSCs migration when compared to untreated UCB-MSCs ((C) of FIG. 9). In contrast, there were no significant differences in UCB-MSCs migration in cultures treated with MCP-1 ((D) of FIG. 9). This data indicates that IL-8 and GRO-.alpha. participate in UCB-MSCs migration toward U-87 MG cells.

[0022] The co-relationship between the concentration of IL-8 secreted by each cancer cell and UCB-MSCs migration was measured. As a result, U-87 MG, which migrated the highest concentration of UCB-MSCs, showed the highest IL-8 production (FIG. 10A). The inventor also measured IL-8 secretion level in various glioma cells. All tested glioma cell lines which were target cells of UCB-MSC tropism also showed high secretion level of IL-8 ((B) of FIG. 10). This data suggested that UCB-MSCs had a strong migration attraction toward IL-8 secreting cells. In order to identify this, IL-8 was artificially overexpressed in A549 that is a low level of IL-8 expressing human lung cancer cells and then, A549 overexpressing IL-8 and UCB-MSCs were co-cultured. As a result, it was found that although the UCB-MSCs had a poor migration attraction toward A549, UCB-MSCs had a strong migration attraction toward A549 overexpressing IL-8. Therefore, IL-8 could be a strong inducer of UCB-MSCs (see FIG. 10C).

[0023] The inventors of the present invention compared migration characteristics of BM-MSCs and UCB-MSCs with respect to U-87 MG cells or IL-8. As a result, it was found that UCB-MSCs migrate more strongly toward U-87 MG cells or IL-8 than BM-MSCs. UCB-MSCs migration is enhanced dramatically in response to IL-8 treatment, but BM-MSCs migration is weak in response to IL-8 treatment (see FIG. 11).

[0024] Expression levels of CXC chemokine receptor 1 (CXCR1) and CXC chemokine receptor 2 (CXCR2) in UCB-MSCs and BM-MSCs were compared by measuring mRNA and protein (see FIG. 12). RT-PCR analysis using total RNA isolated from UCB-MSCs and BM-MSCs reveal that the PCR product of both CXCR1 and CXCR2 has a higher intensity in UCB-MSCs when compared to BM-MSCs. In regard of protein expression of CXCR1 and CXCR2, CXCR1 and CXCR2 are highly expressed both in UCB-MSCs and BM-MSCs. Since IL-8 has a high affinity to CXCR1 and CXCR2, increased UCB-MSCs migration toward U-87 MG may be due to up-regulated expression of CXCR1 and CXCR2.

[0025] The inventors of the present invention performed an experiment of introducing a gene coding green fluorescent protein (GFP) into UCB-MSCs. As a result, it was found that GFP was successfully introduced and expressed (see FIG. 13). Also, it was found that UCB-MSCs overexpressing the gene coding GFP also have a tropism for U87 MG (see FIG. 14). Such results show that UCB-MSCs to which a gene or a product thereof is introduced can be transferred to cells secreting IL-8 or GRO-.alpha..

[0026] Based on the results described above, the present invention relates to a method of transferring a gene or product thereof to a cell expressing IL-8 or GRO-.alpha. by using UCB-MSCs. The present invention also relates to UCB-MSCs containing a therapeutical composition for transferring a therapeutical or marker gene or a product thereof to a cell that expresses IL-8 or GRO-.alpha. and drives tropism of UCB-MSCs. The present invention also relates to a therapeutical pharmaceutical composition, a kit, a use for preventing or treating brain tumors, and a treatment method of brain tumors, using UCB-MSCs. The present invention also relates to a composition, a kit for diagnosing brain tumors or monitoring the progression of brain tumor treatment and a diagnosing method of brain tumor or monitoring method of the progression of brain tumor treatment, using UCB-MSCs.

[0027] Specifically, the present inventive concept relates to:

[0028] [1] a pharmaceutical composition for preventing or treating brain tumors, wherein the pharmaceutical composition comprises a UCB-MSC;

[0029] [2] a pharmaceutical composition for preventing or treating brain tumors, wherein the pharmaceutical composition comprises a UCB-MSC, wherein the UCB-MSC functions as a carrier for gene therapy for brain tumors;

[0030] [3] a pharmaceutical composition for preventing or treating brain tumors, wherein the pharmaceutical composition comprises a UCB-MSC, wherein an anti-tumor gene is introduced to the UCB-MSC;

[0031] [4] a pharmaceutical composition for preventing or treating brain tumors, wherein the pharmaceutical composition comprises a UCB-MSC, wherein an anti-tumor gene is introduced to the UCB-MSC, wherein the anti-tumor gene is selected from a tumor suppressor gene, an apoptosis-inducing factor gene, a cell cycle regulatory gene, and an angiogenesis inhibitor gene;

[0032] [5] a pharmaceutical composition for preventing or treating brain tumors, wherein the pharmaceutical composition comprises a UCB-MSC, wherein an anti-tumor gene is introduced to the UCB-MSC, wherein the anti-tumor gene is selected from a tumor suppressor gene, an apoptosis inducing factor gene, a cell cycle regulatory gene, and an angiogenesis inhibitor gene, wherein the tumor suppressor gene may be selected from the group consisting of a gene of phosphatase and tensin homolog (PTEN), a gene of Maspin, a gene of RUNX3, a gene of Caveolin-1, a gene of nm23, a gene of Rb protein, a gene of Brush-1, a gene of inhibitor of tumor growth (ING-4), a gene of survivin, a gene of X chromosome linked inhibitor apoptosis protein (XIAP), a gene of neural apoptosis inhibitory protein (NAIP), and genes of proteins regulating these genes;

[0033] [6] a pharmaceutical composition for preventing or treating brain tumors, wherein the pharmaceutical composition comprises a UCB-MSC, wherein an anti-tumor gene is introduced to the UCB-MSC, wherein the anti-tumor gene is selected from a tumor suppressor gene, an apoptosis-inducing factor gene, a cell cycle regulatory gene, and an angiogenesis inhibitor gene, wherein the apoptosis-inducing factor gene may be selected from the group consisting of a gene of cytokine, a gene of interleukin, a gene of a tumor necrosis factor (TNF), a gene of interferon (INF-.alpha., INF-.beta., INF-.gamma.), a gene of a colony stimulating factor (CSFs), a gene of p53, a gene of Apaf-1, a gene of TRAIL, a gene of Caspase, a gene of Bax, a gene of Bad, a gene of FADD, a gene of JNK, a gene of p38 kinase, and genes of proteins regulating these genes;

[0034] [7] a pharmaceutical composition for preventing or treating brain tumors, wherein the pharmaceutical composition comprises a UCB-MSC, wherein an anti-tumor gene is introduced to the UCB-MSC, wherein the anti-tumor gene is selected from a tumor suppressor gene, an apoptosis-inducing factor gene, a cell cycle regulatory gene, and an angiogenesis inhibitor gene, wherein the cell cycle regulatory gene may be selected from the group consisting of a gene of cdc2, a gene of Cyclin (Cyclin A, Cyclin D, Cyclin E), a gene of cdc25C, a gene of WAF, a gene of INK4, a gene of CDK (CDK1, CDK2, CDK4, CDK6), a gene of Rb protein, a gene of E2F, an antisense or SiRNA thereof, and genes of proteins regulating these genes;

[0035] [8] a pharmaceutical composition for preventing or treating brain tumors, wherein the pharmaceutical composition comprises a UCB-MSC, wherein an anti-tumor gene is introduced to the UCB-MSC, wherein the anti-tumor gene is selected from a tumor suppressor gene, an apoptosis-inducing factor gene, a cell cycle regulatory gene, and an angiogenesis inhibitor gene, wherein the angiogenesis inhibitor gene may be selected from the group consisting of a gene of thrombospondin-1, a gene of endostatin, a gene of tumstatin, a gene of canstatin, a gene of vastatin, a gene of restin, a gene of a vascular endothelial growth inhibitor, a gene of maspin, a gene of angiopoietins, a gene of 16-kd prolactin fragment, and a gene of endorepellin;

[0036] [9] a pharmaceutical composition for preventing or treating brain tumors, wherein the pharmaceutical composition comprises a UCB-MSC, wherein a prodrug converting enzyme gene is introduced to the UCB-MSC;

[0037] [10] a pharmaceutical composition for preventing or treating brain tumors, wherein the pharmaceutical composition comprises a UCB-MSC, wherein a prodrug converting enzyme gene is introduced to the UCB-MSC, wherein the prodrug converting enzyme gene is selected from cytosine deaminase and CYP2B1 gene;

[0038] [11] a pharmaceutical composition for preventing or treating brain tumors, wherein the pharmaceutical composition comprises a UCB-MSC, wherein an antisense or SiRNA of a gene related to a brain tumor is introduced to the UCB-MSC;

[0039] [12] a pharmaceutical composition for preventing or treating brain tumors, wherein the pharmaceutical composition comprises a UCB-MSC, wherein an antisense or SiRNA of a gene related to a brain tumor is introduced to the UCB-MSC, wherein the gene related to a brain tumor may be selected from the group consisting of a gene of Ras family, a gene of c-myc, a gene of abl, a gene of erbB-1, a gene of EGF-R, a gene of Bax, a gene of Apaf-1 interacting protein (APIP), a gene of Wnt-1-induced secreted protein 1 (WISP-1), a gene of Wnt, a gene of Raf-1, a gene of Src, a gene of Akt, a gene of Erk-1,2 and a gene of BcL-2;

[0040] [13] a pharmaceutical composition for preventing or treating brain tumors, wherein the pharmaceutical composition comprises a UCB-MSC, wherein an oncolytic virus is introduced to the UCB-MSC;

[0041] [14] a pharmaceutical composition for preventing or treating brain tumors, wherein the pharmaceutical composition comprises a UCB-MSC, wherein an oncolytic virus is introduced to the UCB-MSC, wherein the oncolytic virus is selected from Herpes simplex virus and Reovirus type 3;

[0042] [15] any one of the pharmaceutical compositions for preventing or treating brain tumors described above, wherein the brain tumor is selected from the group consisting of Astrocytoma, Pilocytic astrocytoma, Low-grade Astrocytoma, Anaplastic Astrocytoma, Glioblastoma Multiforme, Brain Stem Glioma, Ependymoma, Subependymoma, Ganglioneuroma, Mixed Glioma, Oligodendroglioma, Optic Nerve Glioma, Acoustic Neuroma, Chordoma, CNS Lymphoma, Craniopharyngioma, Hemangioblastoma, Medulloblastoma, Meningioma, Pineal Tumors, Pituitary Tumors, Primitive Neuroectodermal Tumors, Rhabdoid Tumors, Schwannoma, Cysts, Neurofibromatosis, Pseudotumor Cerebri and Tuberous Sclerosis;

[0043] [16] a composition for diagnosing brain tumors or monitoring brain tumor treatment progression, wherein the composition includes a UCB-MSC;

[0044] [17] a composition for diagnosing brain tumors or monitoring brain tumor treatment progression, wherein the composition includes a UCB-MSC, wherein the UCB-MSC is labeled with a detectable marker;

[0045] [18] a composition for diagnosing brain tumors or monitoring brain tumor treatment progression, wherein the composition includes a UCB-MSC, wherein the UCB-MSC is labeled to with a detectable marker, wherein the detectable marker is selected from luciferase-containing enzyme-based fluorescent detector and Tat peptide-derivatized magnetic nanoparticles;

[0046] [19] any one of the compositions for diagnosing brain tumors or monitoring brain tumor treatment progression, wherein the brain tumor is selected from the group consisting of Astrocytoma, Pilocytic astrocytoma, Low-grade Astrocytoma, Anaplastic Astrocytoma, Glioblastoma Multiforme, Brain Stem Glioma, Ependymoma, Subependymoma, Ganglioneuroma, Mixed Glioma, Oligodendroglioma, Optic Nerve Glioma, Acoustic Neuroma, Chordoma, CNS Lymphoma, Craniopharyngioma, Hemangioblastoma, Medulloblastoma, Meningioma, Pineal Tumors, Pituitary Tumors, Primitive Neuroectodermal Tumors, Rhabdoid Tumors, Schwannoma, Cysts, Neurofibromatosis, Pseudotumor Cerebri, and Tuberous Sclerosis;

[0047] [20] a kit for treating brain tumors, including: an expression vector having a prodrug converting enzyme gene; an UCB-MSC; and an prodrug of anticancer drug;

[0048] [21] a kit for treating brain tumors, including: an expression vector having a prodrug converting enzyme gene; an UCB-MSC; and an prodrug of anticancer drug, wherein the prodrug converting enzyme gene is selected from a cytosine deaminase gene and a CYP2B1 gene;

[0049] [22] a kit for treating brain tumors, including: an expression vector having a prodrug converting enzyme gene; an UCB-MSC; and an prodrug of anticancer drug, wherein the prodrug converting enzyme gene is selected from a cytosine deaminase gene and a CYP2B1 gene, wherein the UCB-MSC is transfected with the expression vector having a prodrug converting enzyme gene;

[0050] [23] any one of the kits described above, wherein the brain tumor is selected from the group consisting of Astrocytoma, Pilocytic astrocytoma, Low-grade Astrocytoma, Anaplastic Astrocytoma, Glioblastoma Multiforme, Brain Stem Glioma, Ependymoma, Subependymoma, Ganglioneuroma, Mixed Glioma, Oligodendroglioma, Optic Nerve Glioma, Acoustic Neuroma, Chordoma, CNS Lymphoma, Craniopharyngioma, Hemangioblastoma, Medulloblastoma, Meningioma, Pineal Tumors, Pituitary Tumors, Primitive Neuroectodermal Tumors, Rhabdoid Tumors, Schwannoma, Cysts, Neurofibromatosis, Pseudotumor Cerebri and Tuberous Sclerosis;

[0051] [24] a gene therapy composition for transferring a therapeutical gene or product thereof to a cell, wherein the gene therapy composition includes a UCB-MSC, wherein the cell expresses IL-8 or GRO-.alpha. and induces tropism of the UCB-MSC;

[0052] [25] a gene therapy composition for transferring a therapeutical gene or product thereof to a cell, wherein the gene therapy composition includes a UCB-MSC, wherein the cell expresses IL-8 or GRO-.alpha. and induces tropism of the UCB-MSC, wherein the UCB-MSC function as a to carrier for gene therapy;

[0053] [26] a gene therapy composition for transferring a therapeutical gene or product thereof to a cell, wherein the gene therapy composition includes a UCB-MSC, wherein the cell expresses IL-8 or GRO-.alpha. and induces tropism of the UCB-MSC, wherein an anti-tumor gene is introduced to the UCB-MSC;

[0054] [27] a gene therapy composition for transferring a therapeutical gene or product thereof to a cell, wherein the gene therapy composition includes a UCB-MSC, wherein the cell expresses IL-8 or GRO-.alpha. and induces a tropism of the UCB-MSC, wherein an anti-tumor gene is introduced to the UCB-MSC, wherein the anti-tumor gene is selected from the group consisting of a tumor suppressor gene, an apoptosis-inducing factor gene, a cell cycle regulatory gene, and an angiogenesis inhibitor gene;

[0055] [28] a gene-treating composition for transferring a therapeutical gene or product thereof to a cell, wherein the gene therapy composition includes a UCB-MSC, wherein the cell expresses IL-8 or GRO-.alpha. and induces a tropism of the UCB-MSC, wherein an anti-tumor gene is introduced to the UCB-MSC, wherein the anti-tumor gene is selected from the group consisting of a tumor suppressor gene, an apoptosis-inducing factor gene, a cell cycle regulatory gene, and an angiogenesis inhibitor gene, wherein the tumor suppressor gene may be selected from the group consisting of a gene of phosphatase and tensin homolog (PTEN), a gene of Maspin, a gene of RUNX3, a gene of Caveolin-1, a gene of nm23, a gene of Rb protein, a gene of Brush-1, a gene of inhibitor of tumor growth (ING-4), a gene of survivin, a gene of X chromosome linked inhibitor apoptosis protein (XIAP), a gene of neural apoptosis inhibitory protein (NAIP), and genes of proteins regulating these genes;

[0056] [29] a gene therapy composition for transferring a therapeutical gene or product thereof to a cell, wherein the gene therapy composition includes a UCB-MSC, wherein the cell expresses IL-8 or GRO-.alpha. and induces a tropism of the UCB-MSC, wherein an anti-tumor gene is introduced to the UCB-MSC, wherein the anti-tumor gene is selected from the group consisting of a tumor suppressor gene, an apoptosis-inducing factor gene, a cell cycle regulatory gene, and an angiogenesis inhibitor gene, wherein the apoptosis-inducing factor gene may be selected from the group consisting of a gene of cytokine, a gene of interleukin, a gene of a tumor necrosis factor (TNF), a gene of interferon (INF-.alpha., INF-.beta., INF-.gamma.), a gene of a colony stimulating factor (CSFs), a gene of p53, a gene of Apaf-1, a gene of TRAIL, a gene of Caspase, a gene of Bax, a gene of Bad, a gene of FADD, a gene of JNK, a gene of p38 kinase, and genes of proteins regulating these genes;

[0057] [30] a gene therapy composition for transferring a therapeutical gene or product thereof to a cell, wherein the gene therapy composition includes a UCB-MSC, wherein the cell expresses IL-8 or GRO-.alpha. and induces tropism of the UCB-MSC, wherein an anti-tumor gene is introduced to the UCB-MSC, wherein the anti-tumor gene is selected from the group consisting of a tumor suppressor gene, an apoptosis-inducing factor gene, a cell cycle regulatory gene, and an antiogenesis inhibitor gene, wherein the cell cycle regulatory gene may be selected from the group consisting of a gene of cdc2, a gene of Cyclin (Cyclin A, Cyclin D, Cyclin E), a gene of cdc25C, a gene of WAF, a gene of INK4, a gene of CDK (CDK1, CDK2, CDK4, CDK6), a gene of Rb protein, a gene of E2F, an antisense or SiRNA thereof, and genes of proteins regulating these genes;

[0058] [31] a gene therapy composition for transferring a therapeutical gene or product thereof to a cell, wherein the gene therapy composition includes a UCB-MSC, wherein the cell expresses IL-8 or GRO-.alpha. and induces a tropism of the UCB-MSC, wherein an anti-tumor gene is introduced to the UCB-MSC, wherein the anti-tumor gene is selected from the group consisting of a tumor suppressor gene, an apoptosis-inducing factor gene, a cell cycle regulatory gene, and an antiogenesis inhibitor gene, wherein the angiogenesis inhibitor gene may be selected from the group consisting of a gene of thrombospondin-1, a gene of endostatin, a gene of tumstatin, a gene of canstatin, a gene of vastatin, a gene of restin, a gene of a vascular endothelial growth inhibitor, a gene of maspin, a gene of angiopoietins, a gene of 16-kd prolactin fragment, and a gene of endorepellin;

[0059] [32] a gene therapy composition for transferring a therapeutical gene or product thereof to a cell, wherein the gene therapy composition includes a UCB-MSC, wherein the cell expresses IL-8 or GRO-.alpha. and induces a tropism of the UCB-MSC, wherein a prodrug converting enzyme gene is introduced to the UCB-MSC;

[0060] [33] a gene therapy composition for transferring a therapeutical gene or product thereof to a cell, wherein the gene therapy composition includes a UCB-MSC, wherein the cell expresses IL-8 or GRO-.alpha. and induces a tropism of the UCB-MSC, wherein a prodrug converting enzyme gene is introduced to the UCB-MSC, wherein the prodrug converting enzyme gene is selected from the group consisting of cytosine deaminase gene and a CYP2B1 gene;

[0061] [34] a gene therapy composition for transferring a therapeutical gene or product thereof to a cell, wherein the gene therapy composition includes a UCB-MSC, wherein the cell expresses IL-8 or GRO-.alpha. and induces a tropism of the UCB-MSC, wherein an antisense or SiRNA of a gene related to a tumor is introduced to the UCB-MSC;

[0062] [35] a gene therapy composition for transferring a therapeutical gene or product thereof to a cell, wherein the gene therapy composition includes a UCB-MSC, wherein the cell expresses IL-8 or GRO-.alpha. and induces a tropism of the UCB-MSC, wherein an antisense or SiRNA of a gene related to a tumor is introduced to the UCB-MSC, wherein the gene related to a tumor may be selected from the group consisting of a gene of Ras family, a gene of c-myc, a gene of abl, a gene of erbB-1, a gene of EGF-R, a gene of Bax, a gene of an Apaf-1 interacting protein (APIP), a gene of Wnt-1-induced secreted protein 1 (WISP-1), a gene of Wnt, a gene of Raf-1, a gene of Src, a gene of Akt, a gene of Erk-1,2 and a gene of BcL-2;

[0063] [36] a gene therapy composition for transferring a therapeutical gene or product thereof to a cell, wherein the gene-treating composition includes a UCB-MSC, wherein the cell expresses IL-8 or GRO-.alpha. and induces a tropism of the UCB-MSC, wherein an oncolytic virus is introduced to the UCB-MSC;

[0064] [37] a gene therapy composition for transferring a therapeutical gene or product thereof to a cell, wherein the gene therapy composition includes a UCB-MSC, wherein the cell expresses IL-8 or GRO-.alpha. and induces a tropism of the UCB-MSC, wherein a oncolytic virus is introduced to the UCB-MSC, wherein the oncolytic virus is selected from the group consisting of Herpes simplex virus and Reovirus type 3;

[0065] [38] a composition for diagnosing a disease occurring in a site including a cell or monitoring treatment progression of the disease, wherein the composition includes a UCB-MSC, wherein the cell expresses IL-8 or GRO-.alpha. and induces a tropism of the UCB-MSC;

[0066] [39] a composition for diagnosing a disease occurring in a site including a cell or monitoring treatment progression of the disease, wherein the composition includes a UCB-MSC, wherein the cell expresses IL-8 or GRO-.alpha. and induces a tropism of the UCB-MSC, wherein the UCB-MSC is labeled with a detectable marker; and

[0067] [40] a composition for diagnosing a disease occurring in a site including a cell or monitoring treatment progression of the disease, wherein the composition includes a UCB-MSC, wherein the cell expresses IL-8 or GRO-.alpha. and induces a tropism of the UCB-MSC, wherein the UCB-MSC is labeled with a detectable marker, wherein the detectable marker may be selected from the group consisting of a luciferase-containing enzyme based fluorescent detector and Tat peptide-derivatized magnetic nanoparticles.

[0068] An aspect of the present invention provides a method of preventing or treating a tumor comprising administering to a subject an effective dose of a composition comprising mesenchymal stem cells derived from umbilical cord blood (UCB-MSC).

[0069] In the method, the administration may be made by using any known method in the art. The administration may be made for example, by a parenteral administration. The parenteral administration includes an injection. The injection may be made intravascullary, intramuscularly, subcutaneously, intradermally, or intrathecally. the administration may be made systemically or locally. The local administration may include direct administration to the tumor tissue. The composition may be administered into the subject alone or in combination with any anti-cancer drug or prodrug known in the art.

[0070] Since UCB-MSCs do not express HLA-DR (Major Histocompatibility Complex class II) that is a major cause for immunological rejection when a tissue or organ is transplanted (see Le Blanc, K C, Exp Hematol, 31:890-896, 2003; and Tse W T et al., Transplantation, 75:389-397, 2003), immunological reactions, such as rejection, which are major problems of transplantation do not occur or can be minimized. Accordingly, UCB-MSCs included in the pharmaceutical composition or used in the method according to the present invention can be taken from, in addition to a self-derived UCB, another subject-derived UCB. According to the present invention, UCB-MSCs can be used after being cryopreserved.

[0071] The UCB-MSCs-containing pharmaceutical composition for gene therapy or for preventing or treating diseases according to the present invention may further include pharmaceutically acceptable additives, in addition to the effective component. The UCB-MSCs-containing pharmaceutical composition may be formed into a suitable formulation that can be administered to a body. The suitable formulation may be a non-oral administration formulation, such as an injectable formulation or a locally administrable formulation. For example, a sterilized solution or suspension that includes water or a pharmaceutically acceptable solvent can be non-orally administered in an injectable form. Specifically, water or the pharmaceutically acceptable solvent is appropriately combined with a pharmaceutically acceptable carrier or medium, thereby forming an injectable formulation in a conventionally acceptable unit dosage. Examples of the pharmaceutically acceptable carrier or medium may include sterile water, saline, vegetable oils, emulsifier, suspension, surfactant, stabilizer, excipient, vehicle, an antiseptic substance, a binder, etc.

[0072] The injectable formulation described above can be non-orally administered, specifically directly administered to a site of disease, by using a conventional method. Alternatively, the injectable formulation described above can be administered through a cerebrospinal fluid, a vein, or an artery supplying blood to the site of disease, preferably directly administered to neighboring portions of the site of disease in the brain or the spinal cord or the opposite portions thereto. For example, the injectable formulation described can be administered using a clinical method developed by Douglas Kondziolka in Pittsburgh in 1998. That is, a skull of a subject to be administered is cut to a diameter of about 1 cm, the size of a pea, and then a MSC solution mixed with a Hank's balanced salt solution (HBSS) is injected thereto. In this regard, the injecting the MSC solution is performed using an injector including a long needle and a stereotactic frame for accurately injecting the MSC solution into the brain.

[0073] The daily dose of UCB-MSCs may be 1.times.10.sup.4 to 1.times.10.sup.7 cells/kg body weight, preferably 5.times.10.sup.5 to 5.times.10.sup.6 cells/kg body weight. The daily dose may be administered at once or be divided for several treatments. However, according to the present invention, the administration dose of UCB-MSCs may vary according to the kinds of diseases to be treated, the severity of disease to be treated, administration routes, and the weight, age, and gender of a patient. Accordingly, the administration dose described above does not limit the scope of the present invention.

[0074] In the method, the UCB-MSC may be obtained by any known method in the art. For example, to isolate a monocyte including a MSC from an UCB, any known method such as the method disclosed in Korean Registered Patent No. 489248 filed by the applicant of the present application and registered can be used. For example, the isolating method may be a ficoll-Hypaque density gradient method, but is not limited thereto. Specifically, UCB taken from an umbilical vein after delivery and before the placenta is separated is centrifuged with a ficoll-hypaque gradient to obtain a monocyte, and then the monocyte is washed several times to remove impurities therefrom. The resultant monocyte can be directly used for isolation or culture of MSCs, or cryo preserved for a long period of time.

[0075] A MSC can be isolated from UCB and cultured using any known method (see Pittinger M F et al. Science, 284: 143-7, 1999; and Lazarus H M et al. Bone Marrow Transplant, 16: 557-64, 1995), such as a method disclosed in Korean Publicated Patent No. 2003-0069115.

[0076] First, the isolated UCB may be centrifuged with, for example, a ficoll-Hypaque gradient to separate monocytes including a hematopoietic cell and a MSC, and then, the monocyte may be washed several times to remove impurities therefrom. Then, monocytes may be seeded in an appropriate concentration in a culture dish to grow cells in a form of a single layer. These cells may be identified with a phase-contrast microscope. In the phase-contrast microscopic image, colonies of cells having a homogeneous spindle shape are MSCs. Then, when cells are cultured and grow, cells are sub-cultured and then multiplied until the number of the cells reaches a desired number.

[0077] The UCB-MSCs included in the composition or used in the method according to the present invention can be cryopreserved using known methods (see Campos et al., Cryobiology 35:921-924, 1995). A medium for the cryoporeserving process may include 10.about.20% fetal bovine serum (FBS) and 10% dimethylsulfoxide (DMSO). The cells may be suspended in the medium until the concentration of cells is about 1.times.10.sup.6 to 5.times.10.sup.6 cells per 1 mL of medium.

[0078] The cell suspension may be divided and each part may be loaded onto a glass or plastic ample for cryopreservation, and then, the sample may be sealed and loaded into a temperature-controlled programmed freezer. Cells may be frozen using a freezing program providing a temperature change of -1.degree. C./minute so that damage to cells can be reduced when frozen cells are thawed. When the temperature of the sample reaches -90.degree. C. or lower, the sample is moved to a liquid nitrogen storage tank having a temperature of -150.degree. C. or lower.

[0079] When the frozen cells are thawed, the sample is quickly moved from the liquid nitrogen storage tank to a water bath having a controlled temperature of 37.degree. C. The thawed content in the ample is immediately moved to a culture dish containing a culture medium in a stabilized condition.

[0080] A culture medium for isolating and culturing a MSC may be a cell culture medium containing 10% to 30% of FBS. The cell culture medium may be any cell culture medium that is conventionally used in the art. Examples of the cell culture medium may include a medium selected from the group consisting of a DMEM medium, an MEM medium, a .alpha.-MEM medium, a McCoys 5A medium, an eagle's basal medium, a CMRL medium, a Glasgow minimum necessarily medium, a (Ham's) F-12 medium, an iscove's modified Dulbecco's medium (IMDM), a (Liebovitz') L-15 medium, a RPMI 1640 medium and a combination thereof. For example, the cell culture medium may be the DMEM medium. During culturing, cells may be suspended so that the concentration of cells is about 5.times.10.sup.3 to 2.times.10.sup.4 cells per 1 mL of the medium.

[0081] Also, the cell culture medium may further include one or more additives, if required. The additives may include at least one material selected from the group consisting of: a serum of fetal calf, horse or human; a penicillin G for preventing microorganism contamination; antibiotics such as streptomycin sulfate or gentamycin; antifungal agents such as amphotericin B or nystatin; and mixtures of at least two materials selected from the forgoing.

[0082] In the method, the UCB-MSCs may be genetically engineered so as to transfer a therapeutic drug for substantially inhibiting growth of brain tumor cells. Also, the UCB-MSCs may be genetically engineered so as to transfer a therapeutical gene or product thereof to cells secreting IL-8 or GRO-.alpha.. In this regard, the term "inhibiting" refers to inhibiting cell is proliferation and growth, in addition necrosis and apoptosis. The therapeutical gene may be, for example, an anti-tumor gene, a gene of an enzyme converting a prodrug into a drug, an antisense or SiRNA of a gene related to a tumor, or oncolytic virus (see Yip S et al., The Cancer J. 9(3), 189-204, 2003).

[0083] The UCB-MSC may be for example, an UCB-MSC that an anti-tumor agent gene is introduced thereinto. The anti-tumor agent gene may be for example, an agent selected from the group consisting of a tumor suppressor gene, an apoptosis-inducing factor gene, a cell cycle regulatory factor gene and an angiogenesis inhibitor gene. The tumor suppressor gene may be a gene selected from the group consisting of a gene encoding phosphatase and tensin homolog (PTEN), a gene encoding Maspin, a gene encoding RUNX3, a gene encoding Caveolin-1, a gene encoding nm23, a gene encoding Rb protein, a gene encoding Brush-1, a gene encoding inhibitor of tumor growth (ING-4), a gene encoding survivin, a gene encoding X chromosome linked inhibitor apoptosis protein (XIAP), a gene encoding neural apoptosis inhibitory protein (NAIP), genes encoding proteins related to regulation of said genes and a combination thereof.

[0084] The PTEN gene was identified as a tumor suppressor that is mutated in a large number of cancers at high frequency. The protein encoded this gene is a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It contains a tensin like domain as well as a catalytic domain similar to that of the dual specificity protein tyrosine phosphatases. Unlike most of the protein tyrosine phosphatases, this protein preferentially dephosphorylates phosphoinositide substrates. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating AKT/PKB signaling pathway. The PTEN may have an amino acid sequence of SEQ ID NO: 9. The PTEN gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 9.

[0085] Maspin (mammary serine proteinase inhibitor), a member of the serpin superfamily, has a multitude of effects on cells and tissues at an assortment of developmental stages. Maspin has tumor suppressing activity against breast and prostate cancer. The Maspin may have an amino acid sequence of SEQ ID NO: 10. The Maspin gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 10.

[0086] RUNX3 (RUNT-related transcription factor 3) gene encodes a member of the runt domain-containing family of transcription factors. A heterodimer of this protein and a beta subunit forms a complex that binds to the core DNA sequence 5'-PYGPYGGT-3' found in a number of enhancers and promoters, and can either activate or suppress transcription. It also interacts with other transcription factors. It functions as a tumor suppressor, and the gene is frequently deleted or transcriptionally silenced in cancer. Multiple transcript variants encoding different isoforms have been found for this gene. The RUNX3 may have an amino acid sequence of SEQ ID NO: 11 (isoform 1) or 12 (isoform 2). The RUNX3 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 11 or 12.

[0087] Caveolin 1 (CAV1), a scaffolding protein, is the main component of the caveolae plasma membranes found in most cell types. The protein links integrin subunits to the tyrosine kinase FYN, an initiating step in coupling integrins to the Ras-ERK pathway and promoting cell cycle progression. The gene is a tumor suppressor gene candidate and a negative regulator of the Ras-p42/44 MAP kinase cascade. CAV1 and CAV2 are located next to each other on chromosome 7 and express colocalizing proteins that form a stable hetero-oligomeric complex. By using alternative initiation codons in the same reading frame, two isoforms (alpha and beta) are encoded by a single transcript from caveolin 1 gene. The CAVEOLIN 1 may have an amino acid sequence of SEQ ID NO: 13. The CAVEOLIN 1 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 13.

[0088] NM23 gene (NME1; nonmetastatic cells 1, protein expressed in) was identified because of its reduced mRNA transcript levels in highly metastatic cells. Nucleoside diphosphate kinase (NDK) exists as a hexamer composed of `A` (encoded by this gene) and `B` (encoded by NME2) isoforms. Mutations in this gene have been identified in aggressive neuroblastomas. Two transcript variants encoding different isoforms have been found for this gene. Co-transcription of this gene and the neighboring downstream gene (NME2) generates naturally-occurring transcripts (NME1-NME2), which encodes a fusion protein comprised of sequence sharing identity with each individual gene product. The NM23 may have an amino acid sequence of SEQ ID NO: 14 (isoform A) or 15 (isoform B). The NM23 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 14 or 15.

[0089] The protein encoded by Rb (Retinoblastoma; Rb1) gene is a negative regulator of the cell cycle and was the first tumor suppressor gene found. The encoded protein also stabilizes constitutive heterochromatin to maintain the overall chromatin structure. The active, hypophosphorylated form of the protein binds transcription factor E2F1. Defects in this gene are a cause of childhood cancer retinoblastoma (RB), bladder cancer, and osteogenic sarcoma. The Rb may have an amino acid sequence of SEQ ID NO: 16. The Rb gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 16.

[0090] The protein encoded by Brush-1 (Myosin IA; MYOIA; BBMI) gene belongs to the myosin superfamily. Myosins are molecular motors that, upon interaction with actin filaments, utilize energy from ATP hydrolysis to generate mechanical force. Each myosin has a conserved N-terminal motor domain that contains both ATP-binding and actin-binding sequences. Following the motor domain is a light-chain-binding `neck` region containing 1-6 copies of a repeat element, the IQ motif, that serves as a binding site for calmodulin or other members of the EF-hand superfamily of calcium-binding proteins. At the C-terminus, each myosin class has a distinct tail domain that serves in dimerization, membrane binding, protein binding, and/or enzymatic activities and targets each myosin to its particular subcellular location. The kidney epithelial cell line, LLC-PK1-CL4 (CL4), forms a well ordered brush border (BB) on its apical surface. Experiments indicate that the brush border population of the encoded protein turns over rapidly, while its head and tail domains interact transiently with the core actin and plasma membrane, respectively. A rapidly exchanging pool of the protein encoded by this gene envelops an actin core bundle that, by comparison, is static in structure. The Brush-1 may have an amino acid sequence of SEQ ID NO: 17. The Brush-1 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 17.

[0091] ING4 (inhibitor of growth 4) gene encodes a tumor suppressor protein that contains a PHD-finger, which is a common motif in proteins involved in chromatin remodeling. This protein can bind TP53 and EP300/p300, a component of the histone acetyl transferase complex, suggesting its involvement in the TP53-dependent regulatory pathway. Multiple alternatively spliced transcript variants have been observed that encode distinct proteins. The ING4 may have an amino acid sequence of SEQ ID NO: 18 (isoform 1), 19 (isoform 3), 20 (isoform 4), 21 (isoform 5), 22 (isoform 6) or 23 (isoform 9). The ING4 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 18, 19, 20, 21, 22 or 23.

[0092] Survivin (Baculoviral IAP repeat-containing protein 5; BIRC5) gene is a member of the inhibitor of apoptosis (IAP) gene family, which encodes negative regulatory proteins that prevent apoptotic cell death. IAP family members usually contain multiple baculovirus IAP repeat (BIR) domains, but this gene encodes proteins with only a single BIR domain. The encoded proteins also lack a C-terminus RING finger domain. Gene expression is high during fetal development and in most tumors yet low in adult tissues. Antisense transcripts are involved in the regulation of this gene's expression. At least four transcript variants encoding distinct isoforms have been found for this gene, but the full-length natures of only three of them have been determined. The Survivin may have an amino acid sequence of SEQ ID NO: 24 (isoform 1), (isoform 2) or 26 (isoform 3). The Survivin gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 24, 25 or 26.

[0093] The protein encoded by XIAP (Inhibitor of apoptosis, X-linked; Baculoviral IAP repeat-containing protein 4; BIRC4) gene is a member of a family of proteins which inhibit apoptosis through binding to tumor necrosis factor receptor-associated factors TRAF1 and TRAF2. This protein inhibits apoptosis induced by menadione, a potent inducer of free radicals, and ICE. It also inhibits at least two members of the caspase family of cell-death proteases, caspase-3 and caspase-7. The XIAP may have an amino acid sequence of SEQ ID NO: 27. The XIAP gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 27.

[0094] NAIP (Neuronal apoptosis inhibitory protein; baculoviral IAP repeat-containing protein 1; BIRC) gene is part of a 500 kb inverted duplication on chromosome 5q13. This duplicated region contains at least four genes and repetitive elements which make it prone to rearrangements and deletions. The repetitiveness and complexity of the sequence have also caused difficulty in determining the organization of this genomic region. This copy of the gene is full length; additional copies with truncations and internal deletions are also present in this region of chromosome 5q13. It is thought that this gene is a modifier of spinal muscular atrophy caused by mutations in a neighboring gene, SMN1. The protein encoded by this gene contains regions of homology to two baculovirus inhibitor of apoptosis proteins, and it is able to suppress apoptosis induced by various signals. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. The NAIP may have an amino acid sequence of SEQ ID NO: 28 (isoform 1) or SEQ ID NO: 29 (isoform 2). The NAIP gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 28 or 29.

[0095] The apoptosis inducing factor gene may be for example, a gene selected from the group consisting of a gene encoding cytokine, a gene encoding interleukin, a gene encoding a tumor necrosis factor (TNF), a gene encoding interferon (INF-.alpha., INF-.beta., INF-.gamma.), a gene encoding a colony stimulating factor (CSFs), a gene encoding p53, a gene encoding Apaf-1, a gene encoding TRAIL, a gene encoding Caspase, a gene encoding Bax, a gene encoding Bad, a gene encoding to FADD, a gene encoding JNK, a gene encoding p38 kinase and genes encoding proteins related to regulation of said genes.

[0096] TNF (tumor necrosis factor) gene encodes a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is mainly secreted by macrophages. It can bind to, and thus functions through its receptors TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. This cytokine is involved in the regulation of a wide spectrum of biological processes including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. This cytokine has been implicated in a variety of diseases, including autoimmune diseases, insulin resistance, and cancer. Knockout studies in mice also suggested the neuroprotective function of this cytokine. The TNF may have an amino acid sequence of SEQ ID NO: 30. The TNF gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 30.

[0097] INF-.alpha., leukocyte interferon is produced predominantly by B lymphocytes. Immune interferon (IFN-gamma; MIM 147570) is produced by mitogen- or antigen-stimulated T lymphocytes. INF-.beta. is produced by fibroblast. The INF-.alpha. may have an amino acid sequence of SEQ ID NO: 31. The INF-.alpha. gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 31. The INF-.beta. may have an amino acid sequence of SEQ ID NO: 32. The INF-.beta. gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 32. INF-.gamma. or type II interferon is a cytokine critical for innate and adaptive immunity against viral and intracellular bacterial infections and for tumor control. Aberrant INF-.gamma. expression is associated with a number of autoinflammatory and autoimmune diseases. The importance of INF-.gamma. in the immune system stems in part from its ability to inhibit viral replication directly, but most importantly derives from its immunostimulatory and immunomodulatory effects. INF-.gamma. is produced predominantly by natural killer (NK) and natural killer T (NKT) cells as part of the innate immune response, and by CD4 (MIM 186940) and CD8 (see MIM 186910) cytotoxic T lymphocyte (CTL) effector T cells once antigen-specific immunity develops. The INF-.gamma. may have an amino acid sequence of SEQ ID NO: 33. The INF-.gamma. gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 33.

[0098] The CSF may include CSF1, CSF2 or CSF3. CSF1 (COLONY-STIMULATING FACTOR 1) is a cytokine that controls the production, differentiation, and function of macrophages. The active form of the protein is found extracellularly as a disulfide-linked homodimer, and is thought to be produced by proteolytic cleavage of membrane-bound precursors. The encoded protein may be involved in development of the placenta. Four transcript variants encoding three different isoforms have been found for this gene. The CSF1 may have an amino acid sequence of SEQ ID NO: 34 (isoform a precursor), SEQ ID NO: 35 (isoform a precursor), SEQ ID NO: 36 (isoform b precursor) or SEQ ID NO: 37 (isoform c precursor). The CSF1 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 34, 35, 36 or 37.

[0099] CSF2 is a cytokine that controls the production, differentiation, and function of granulocytes and macrophages. The active form of the protein is found extracellularly as a homodimer. CSF2 gene has been localized to a cluster of related genes at chromosome region 5q31, which is known to be associated with interstitial deletions in the 5q-syndrome and acute myelogenous leukemia. Other genes in the cluster include those encoding interleukins 4, 5, and 13. The CSF2 may have an amino acid sequence of SEQ ID NO: 38. The CSF2 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 38.

[0100] CSF3 is a cytokine that controls the production, differentiation, and function of granulocytes. The active protein is found extracellularly. Three transcript variants encoding three different isoforms have been found for this gene. The CSF3 may have an amino acid sequence of SEQ ID NO: 39 (isoform a precursor), SEQ ID NO: 40 (isoform b precursor), or SEQ ID NO: 41 (isoform c). The CSF3 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 39, 40, or 41.

[0101] P53 (Tumor protein p53; TP53) responds to diverse cellular stresses to regulate target genes that induce cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism. p53 protein is expressed at low level in normal cells and at a high level in a variety of transformed cell lines, where it's believed to contribute to transformation and malignancy. p53 is a DNA-binding protein containing transcription activation, DNA-binding, and oligomerization domains. It is postulated to bind to a p53-binding site and activate expression of downstream genes that inhibit growth and/or invasion, and thus function as a tumor suppressor. Mutants of p53 that frequently occur in a number of different human cancers fail to bind the consensus DNA binding site, and hence cause the loss of tumor suppressor activity. Alterations of this gene occur not only as somatic mutations in human malignancies, but also as germline mutations in some cancer-prone families with Li-Fraumeni syndrome. Multiple p53 variants due to alternative promoters and multiple alternative splicing have been found. These variants encode distinct isoforms, which can regulate p53 transcriptional activity. The p53 may have an amino acid sequence of SEQ ID NO: 42 (isoform a), SEQ ID NO: 43 (isoform a), SEQ ID NO: 44 (isoform to b), SEQ ID NO: 45 (isoform c), SEQ ID NO: 46 (isoform d), SEQ ID NO: 47 (isoform e) or SEQ ID NO: 48 (isoform f). The p53 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 42, 43, 44, 45, 46, 47 or 48.

[0102] APAF1 (apoptotic protease activating factor 1) is a cytoplasmic protein that initiates apoptosis. This protein contains several copies of the WD-40 domain, a caspase recruitment domain (CARD), and an ATPase domain (NB-ARC). Upon binding cytochrome c and dATP, this protein forms an oligomeric apoptosome. The apoptosome binds and cleaves caspase 9 preproprotein, releasing its mature, activated form. Activated caspase 9 stimulates the subsequent caspase cascade that commits the cell to apoptosis. Alternative splicing results in several transcript variants encoding different isoforms. The APAF1 may have an amino acid sequence of SEQ ID NO: 49 (isoform a), SEQ ID NO: 50 (isoform b), SEQ ID NO: 51 (isoform c), SEQ ID NO: 52 (isoform d), or SEQ ID NO: 53 (isoform e). The APAF1 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 49, 50, 51, 52, or 53.

[0103] TRAIL (TNF-related apoptosis-inducing ligand; tumor necrosis factor ligand superfamily, member 10; TNFSF10) is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein preferentially induces apoptosis in transformed and tumor cells, but does not appear to kill normal cells although it is expressed at a significant level in most normal tissues. This protein binds to several members of TNF receptor superfamily including TNFRSF10A/TRAILR1, TNFRSF10B/TRAILR2, TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4, and possibly also to TNFRSF11B/OPG. The activity of this protein may be modulated by binding to the decoy receptors TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4, and TNFRSF11B/OPG that cannot induce apoptosis. The binding of this protein to its receptors has been shown to trigger the activation of MAPK8/JNK, caspase 8, and caspase 3. The TRAIL may have an amino acid sequence of SEQ ID NO: 54. The TRAIL gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 54.

[0104] Caspase 3 (apoptosis-related cysteine protease; CASP3) is a protein which is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein cleaves and activates caspases 6, 7 and 9, and the protein itself is processed by caspases 8, 9 and 10. It is the predominant caspase involved in the cleavage of amyloid-beta 4A precursor protein, which is associated with neuronal death in Alzheimer's disease. Alternative splicing of this gene results in two transcript variants that encode the same protein. The Caspase 3 may have an amino acid sequence of SEQ ID NO: 55. The Caspase 3 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 55.

[0105] BAX (BCL2-associated X protein) belongs to the BCL2 protein family. BCL2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein forms a heterodimer with BCL2, and functions as an apoptotic activator. This protein is reported to interact with, and increase the opening of, the mitochondrial voltage-dependent anion channel (VDAC), which leads to the loss in membrane potential and the release of cytochrome c. The expression of this gene is regulated by the tumor suppressor P53 and has been shown to be involved in P53-mediated apoptosis. Multiple alternatively spliced transcript variants, which encode different isoforms, have been reported for this gene. The BAX may have an amino acid sequence of SEQ ID NO: 56. The BAX gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 56.

[0106] BAD (BCL2 antagonist of cell death) is a member of the BCL-2 family. BCL-2 family members are known to be regulators of programmed cell death. This protein positively regulates cell apoptosis by forming heterodimers with BCL-xL and BCL-2, and reversing their death repressor activity. Proapoptotic activity of this protein is regulated through its phosphorylation. Protein kinases AKT and MAP kinase, as well as protein phosphatase calcineurin were found to be involved in the regulation of this protein. Alternative splicing of this gene results in two transcript variants which encode the same isoform. The BAD may have an amino acid sequence of SEQ ID NO: 57. The BAD gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 57.

[0107] FADD (FAS-associated via death domain) is an adaptor molecule that interacts with various cell surface receptors and mediates cell apoptotic signals. Through its C-terminal death domain, this protein can be recruited by TNFRSF6/Fas-receptor, tumor necrosis factor receptor, TNFRSF25, and TNFSF10/TRAIL-receptor, and thus it participates in the death signaling initiated by these receptors. Interaction of this protein with the receptors unmasks the N-terminal effector domain of this protein, which allows it to recruit caspase-8, and thereby activate the cysteine protease cascade. Knockout studies in mice also suggest the importance of this protein in early T cell development. The FADD may have an amino acid sequence of SEQ ID NO: 58. The FADD gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 58.

[0108] JNK1 (C-jun kinase 1; mitogen-activated protein kinase 8; MAPK8) is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is activated by various cell stimuli, and targets specific transcription factors, and thus mediates immediate-early gene expression in response to cell stimuli. The activation of this kinase by tumor-necrosis factor alpha (TNF-alpha) is found to be required for TNF-alpha induced apoptosis. This kinase is also involved in UV radiation induced apoptosis, which is thought to be related to cytochrome c-mediated cell death pathway. Studies of the mouse counterpart of this gene suggested that this kinase play a key role in T cell proliferation, apoptosis and differentiation. Four alternatively spliced transcript variants encoding distinct isoforms have been reported. The JNK1 may have an amino acid sequence of SEQ ID NO: 59 (JNK1 alpha1), SEQ ID NO: 60 (JNK1 alpha2), SEQ ID NO: 61 (JNK1 beta 1) or SEQ ID NO: 62 (JNK1 beta2). The JNK1 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 59, 60, 61 or 62.

[0109] P38 kinase (mitogen-activated protein kinase 14; MAPK14; p38 MAP KINASE; p38-ALPHA) is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is activated by various environmental stresses and proinflammatory cytokines. The activation requires its phosphorylation by MAP kinase kinases (MKKs), or its autophosphorylation triggered by the interaction of MAP3K71P1/TAB1 protein with this kinase. The substrates of this kinase include transcription regulator ATF2, MEF2C, and MAX, cell cycle regulator CDC25B, and tumor suppressor p53, which suggest the roles of this kinase in stress related transcription and cell cycle regulation, as well as in genotoxic stress response. Four alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. The p38 kinase may have an amino acid sequence of SEQ ID NO: 63 (isoform 1). The p38 kinase gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 63.

[0110] The cell cycle regulatory factor gene may be a gene selected from the group consisting of a gene encoding cdc2, a gene encoding Cyclin (Cyclin A, Cyclin D, Cyclin E), a gene encoding cdc25C, a gene encoding WAF, a gene encoding INK4, a gene encoding CDK (CDK1, CDK2, CDK4, CDK6), a gene encoding Rb protein, a gene encoding E2F, an antisense or siRNA thereof and genes encoding proteins related to the regulation of said genes.

[0111] CDC2 (cell division cycle 2, G1 to S and G2 to M; Cyclin-dependent kinase 1; CDK1) is a member of the Ser/Thr protein kinase family. This protein is a catalytic subunit of the highly conserved protein kinase complex known as M-phase promoting factor (MPF), which is essential for G1/S and G2/M phase transitions of eukaryotic cell cycle. Mitotic cyclins stably associate with this protein and function as regulatory subunits. The kinase activity of this protein is controlled by cyclin accumulation and destruction through the cell cycle. The phosphorylation and dephosphorylation of this protein also play important regulatory roles in cell cycle control. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. The CDC2 may have an amino acid sequence of SEQ ID NO: 64 (isoform 2). The CDC2 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 64.

[0112] Cyclin A (Cyclin A2; CCNA2) belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. In contrast to cyclin A1, which is present only in germ cells, this cyclin is expressed in all tissues tested. This cyclin binds and activates CDC2 or CDK2 kinases, and thus promotes both cell cycle G1/S and G2/M transitions. The Cyclin A may have an amino acid sequence of SEQ ID NO: 65. The Cyclin A gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 65.

[0113] The Cyclin D may include Cyclin D2, D3 or combination thereof. Cyclin D2 (CCND2) belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle G1/S transition. This protein has been shown to interact with and be involved in the phosphorylation of tumor suppressor protein Rb. Knockout studies of the homologous gene in mouse suggest the essential roles of this gene in ovarian granulosa and germ cell proliferation. High level expression of this gene was observed in ovarian and testicular tumors. The Cyclin D2 may have an amino acid sequence of SEQ ID NO: 66. The Cyclin D2 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 66. Cyclin D3 (CCND3) belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators to of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle G1/S transition. This protein has been shown to interact with and be involved in the phosphorylation of tumor suppressor protein Rb. The CDK4 activity associated with this cyclin was reported to be necessary for cell cycle progression through G2 phase into mitosis after UV radiation. Several transcript variants encoding different isoforms have been found for this gene. The Cyclin D3 may have an amino acid sequence of SEQ ID NO: 67. The Cyclin D3 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 67. The Cyclin E (CCNE; CYCLIN E1; CCNE1) belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK2, whose activity is required for cell cycle G1/S transition. This protein accumulates at the G1-S phase boundary and is degraded as cells progress through S phase. Overexpression of this gene has been observed in many tumors, which results in chromosome instability, and thus may contribute to tumorigenesis. This protein was found to associate with, and be involved in, the phosphorylation of NPAT protein (nuclear protein mapped to the ATM locus), which participates in cell-cycle regulated histone gene expression and plays a critical role in promoting cell-cycle progression in the absence of pRB. Two alternatively spliced transcript variants of this gene, which encode distinct isoforms, have been described. Two additional splice variants were reported but detailed nucleotide sequence information is not yet available. The CYCLIN E may have an amino acid sequence of SEQ ID NO: 68. The Cyclin E gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 68.

[0114] CDC25C (cell division cycle 25C) gene is highly conserved during evolution and it plays a key role in the regulation of cell division. The CDC25C protein is a tyrosine phosphatase and belongs to the Cdc25 phosphatase family. It directs dephosphorylation of cyclin B-bound CDC2 and triggers entry into mitosis. It is also thought to suppress p53-induced growth arrest. Multiple alternatively spliced transcript variants of this gene have been described, however, the full-length nature of many of them is not known. The CDC25C may have an amino acid sequence of SEQ ID NO: 69 (isoform a) or SEQ ID NO: 70 (isoform b). The CDC25C gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 69 or 70.

[0115] WAF1 (wildtype p53-activated fragment 1; p21) is a potent cyclin-dependent kinase inhibitor. This protein binds to and inhibits the activity of cyclin-CDK2 or -CDK4 complexes, and thus functions as a regulator of cell cycle progression at G1. The expression of this gene is tightly controlled by the tumor suppressor protein p53, through which this protein mediates the p53-dependent cell cycle G1 phase arrest in response to a variety of stress stimuli. This protein can interact with proliferating cell nuclear antigen (PCNA), a DNA polymerase accessory factor, and plays a regulatory role in S phase DNA replication and DNA damage repair. This protein was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a dramatic activation of CDK2, and may be instrumental in the execution of apoptosis following caspase activation. Two alternatively spliced variants, which encode an identical protein, have been reported. The WAF1 may have an amino acid sequence of SEQ ID NO: 71. The CDC25C gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 71.

[0116] INK4 (Cyclin-dependent kinase inhibitor 2A; CDKN2A) gene generates several transcript variants which differ in their first exons. At least three alternatively spliced variants encoding distinct proteins have been reported, two of which encode structurally related isoforms known to function as inhibitors of CDK4 kinase. The remaining transcript includes an alternate first exon located 20 Kb upstream of the remainder of the gene; this transcript contains an alternate open reading frame (ARF) that specifies a protein which is structurally unrelated to the products of the other variants. This ARF product functions as a stabilizer of the tumor suppressor protein p53 as it can interact with, and sequester, MDM1, a protein responsible for the degradation of p53. In spite of the structural and functional differences, the CDK inhibitor isoforms and the ARF product encoded by this gene, through the regulatory roles of CDK4 and p53 in cell cycle G1 progression, share a common functionality in cell cycle G1 control. This gene is frequently mutated or deleted in a wide variety of tumors, and is known to be an important tumor suppressor gene. The INK4 may have an amino acid sequence of SEQ ID NO: 72 (isoform 1), SEQ ID NO: 73 (isoform 3) or SEQ ID NO: 74 (isoform 4). The INK4 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 72, 73 or 74.

[0117] CDK2 (Cyclin-dependent kinase 2) is a member of the Ser/Thr protein kinase family. This protein kinase is highly similar to the gene products of S. cerevisiae cdc28, and S. pombe cdc2. It is a catalytic subunit of the cyclin-dependent protein kinase complex, whose activity is restricted to the G1-S phase, and essential for cell cycle G1/S phase transition. This protein associates with and regulated by the regulatory subunits of the complex including cyclin A or E, CDK inhibitor p21Cip1 (CDKN1A) and p27Kip1 (CDKN1B). Its activity is also regulated by its protein phosphorylation. Two alternatively spliced variants and multiple transcription initiation sites of this gene have been reported. The CDK2 may have an amino acid sequence of SEQ ID NO: 75 (isoform 1) or SEQ ID NO: 76 (isoform 2). The CDK2 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 75 or 76.

[0118] CDK4 (Cyclin-dependent kinase 4) is a member of the Ser/Thr protein kinase family. This protein is highly similar to the gene products of S. cerevisiae cdc28 and S. pombe cdc2. It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16 (INK4a). This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). Mutations in this gene as well as in its related proteins including D-type cyclins, p16 (INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. Multiple polyadenylation sites of this gene have been reported. The CDK4 may have an amino acid sequence of SEQ ID NO: 77. The CDK4 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 77.

[0119] CDK6 (Cyclin-dependent kinase 6) is a member of the cyclin-dependent protein kinase (CDK) family. CDK family members are highly similar to the gene products of Saccharomyces cerevisiae cdc28, and Schizosaccharomyces pombe cdc2, and are known to be important regulators of cell cycle progression. This kinase is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression and G1/S transition. The activity of this kinase first appears in mid-G1 phase, which is controlled by the regulatory subunits including D-type cyclins and members of INK4 family of CDK inhibitors. This kinase, as well as CDK4, has been shown to phosphorylate, and thus regulate the activity of, tumor suppressor protein Rb. The CDK6 may have an amino acid sequence of SEQ ID NO: 78. The CDK6 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 78.

[0120] Transcription factor E2F (E2F Transcription factor 1; E2F1) is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of cell cycle and action of tumor suppressor proteins and is also a target of the transforming proteins of small DNA tumor viruses. The E2F proteins contain several evolutionally conserved domains found in most members of the family. These domains include a DNA binding domain, a dimerization domain which determines interaction with the differentiation regulated transcription factor proteins (DP), a transactivation domain enriched in acidic amino acids, and a tumor suppressor protein association domain which is embedded within the transactivation domain. This protein and another 2 members, E2F2 and E2F3, have an additional cyclin binding domain. This protein binds preferentially to retinoblastoma protein pRB in a cell-cycle dependent manner. It can mediate both cell proliferation and p53-dependent/independent apoptosis. The E2F may have an amino acid sequence of SEQ ID NO: 79. The E2F gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 79.

[0121] The angiogenesis inhibitor gene may be a gene selected from the group consisting of a gene encoding thrombospondin-1, a gene encoding endostatin, a gene encoding tumstatin, a gene encoding canstatin, a gene encoding vastatin, a gene encoding restin, a gene encoding a vascular endothelial growth factor inhibitor, a gene encoding maspin, a gene encoding angiopoietins, a gene encoding 16-kd prolactin fragment and a gene encoding endorepellin.

[0122] Thrombospondin I (THBS1, TSP1)) is a subunit of a disulfide-linked homotrimeric protein. This protein is an adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. This protein can bind to fibrinogen, fibronectin, laminin, type V collagen and integrins alpha-V/beta-1. This protein has been shown to play roles in platelet aggregation, angiogenesis, and tumorigenesis. The thrombospondin 1 may have an amino acid sequence of SEQ ID NO: 80. The thrombospondin 1 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 80.

[0123] Endostatin is contained in collagen, type XVIII, alpha-1 (COL18A1) which is the alpha chain of type XVIII collagen. This collagen is one of the multiplexins, extracellular matrix proteins that contain multiple triple-helix domains (collagenous domains) interrupted by non-collagenous domains. The proteolytically produced C-terminal fragment of type XVIII collagen is endostatin, a potent antiangiogenic protein. Mutations in this gene are associated with Knobloch syndrome. The main features of this syndrome involve retinal abnormalities, so type XVIII collagen may play an important role in retinal structure and in neural tube closure. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. The Endostatin may have an amino acid sequence of SEQ ID NO: 81 (isoform 1) or 82 (isoform 2). The amino acid residues 1340-1510 of SEQ ID NO: 81 (isoform 1) or 1160-1330 residues of SEQ ID NO: 82 (isoform 2) is an endostatin like domain. The Endostatin gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 81 or 82.

[0124] Tumstatin is contained in collagen, type IV, alpha-3 (COL4A3). Type IV collagen, the major structural component of basement membranes, is a multimeric protein composed of 3 to alpha subunits. These subunits are encoded by 6 different genes, alpha 1 through alpha 6, each of which can form a triple helix structure with 2 other subunits to form type IV collagen. This gene encodes alpha 3. In the Goodpasture syndrome, autoantibodies bind to the collagen molecules in the basement membranes of alveoli and glomeruli. The epitopes that elicit these autoantibodies are localized largely to the non-collagenous C-terminal domain of the protein. A specific kinase phosphorylates amino acids in this same C-terminal region and the expression of this kinase is upregulated during pathogenesis. There are multiple alternate transcripts that appear to be unique to this human alpha 3 gene and alternate splicing is restricted to the six exons that encode this C-terminal domain. This gene is also linked to an autosomal recessive form of Alport syndrome. The mutations contributing to this syndrome are also located within the exons that encode this C-terminal region. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter. Some exons of this gene are interspersed with exons of an uncharacterized gene which is on the opposite strand. The tumstatin may have an amino acid sequence of SEQ ID NO: 83. The tumstatin gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 83.

[0125] Canstatin (alpha 2 type IV collagen preproprotein) is one of the six subunits of type IV collagen, the major structural component of basement membranes. The C-terminal portion of the protein, known as canstatin, is an inhibitor of angiogenesis and tumor growth. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter. The canstatin may have an amino acid sequence of SEQ ID NO: 84. The canstatin gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 84.

[0126] The restin (RSN, Reed-Steinbergcell-expressed intermediate filament-associated protein) may have an amino acid sequence of SEQ ID NO: 85. The restin gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 85. VEGI (vascular endothelial growth inhibitor; tumor necrosis factor ligand superfamily, member 15; TNFSF15) is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein is abundantly expressed in endothelial cells, but is not expressed in either B or T cells. The expression of this protein is inducible by TNF and IL-1 alpha. This cytokine is a ligand for receptor TNFRSF25 and decoy receptor TNFRSF21/DR6. It can activate NF-kappaB and MAP kinases, and acts as an autocrine factor to induce apoptosis in endothelial cells. This cytokine is also found to inhibit endothelial cell proliferation, and thus may function as an angiogenesis inhibitor. An additional isoform encoded by an alternatively spliced transcript variant has been reported but the sequence of this transcript has not been determined. The VEGI may have an amino acid sequence of SEQ ID NO: 86. The VEGI gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 86. Angiopoietins are proteins with important roles in vascular development and angiogenesis. All angiopoietins bind with similar affinity to an endothelial cell-specific tyrosine-protein kinase receptor. The protein encoded by this gene is a secreted glycoprotein that activates the receptor by inducing its tyrosine phosphorylation. It plays a critical role in mediating reciprocal interactions between the endothelium and surrounding matrix and mesenchyme. The protein also contributes to blood vessel maturation and stability, and may be involved in early development of the heart. Angiopoietin 1 may have an amino acid sequence of SEQ ID NO: 87. The angiopoietin 1 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 87.

[0127] Prolactin (PRL) may have an amino acid sequence of SEQ ID NO: 88. The prolactin gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 88.

[0128] The endorepellin may have an amino acid sequence of SEQ ID NO: 89. The endorepellin gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 89.

[0129] Further, the UCB-MSC may be for example, an UCB-MSC that a prodrug converting enzyme gene is introduced thereinto. The prodrug converting enzyme gene may be for example, a gene selected from cytosine deaminase gene, CYP2B1 gene and CYP2B6. The cytosine deaminase converte 5-FC into 5-FU that is an anticancer drug, or the cytochrome P-450 CYP2B1 enzyme, encoded by CYP2B1 gene, mediates the activation of at least one compounds selected from the group consisting of cyclophosphamide (CPA) and ifosfamide (IFO) to alkylating metabolites, which are anticancer drugs. The cytosine deaminase gene may include AICDA (activation-induced cytidine deaminase).

[0130] AICDA is a RNA-editing deaminase that is a member of the cytidine deaminase family. The protein is involved in somatic hypermutation, gene conversion, and class-switch recombination of immunoglobulin genes. Defects in this gene are the cause of autosomal recessive hyper-IgM immunodeficiency syndrome type 2 (HIGM2). The AICDA may have an amino acid sequence of SEQ ID NO: 90. The AICDA gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 90.

[0131] CYP2B6 (cytochrome P450, subfamily IIB, polypeptide 6) protein is a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and its expression is induced by phenobarbital. The enzyme is known to metabolize some xenobiotics, such as the anti-cancer drugs cyclophosphamide and ifosphamide. Transcript variants for this gene have been described; however, it has not been resolved whether these transcripts are in fact produced by this gene or by a closely related pseudogene, CYP2B7. Both the gene and the pseudogene are located in the middle of a CYP2A pseudogene found in a large cluster of cytochrome P450 genes from the CYP2A, CYP2B and CYP2F subfamilies on chromosome 19q. The CYP2B6 may have an amino acid sequence of SEQ ID NO: 91. The CYP2B6 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 91.

[0132] In the method of the aspect of the present invention, the method further comprises administering a prodrug of an anticancer drug into the subject. The prodrug may be for example, 5-fluorocytosine (5-FC), which is a prodrug of 5-fluorouracil (5-FU), cyclophosphamide (CPA), ifosfamide (IFO) or a combination thereof.

[0133] The UCB-MSC may be for example, an UCB-MSC that an antisense or siRNA of a gene related to brain tumor is introduced thereinto. The gene related to brain tumor may be for example, a gene selected from the group consisting of a gene encoding a Ras family protein, a gene encoding c-myc, a gene encoding abl, a gene encoding erbB-1, a gene encoding EGFR, a gene encoding Bax, a gene encoding Apaf-1 interacting protein (APIP), a gene encoding Wnt-1-induced secreted protein 1 (WISP-1), a gene encoding Wnt, a gene encoding Raf-1, a gene encoding Src, a gene encoding Akt, a gene encoding Erk-1, 2 and a gene encoding BcL-2.

[0134] Myc (v-myc avian myelocytomatosis viral oncogene homolog) protein is a multifunctional, nuclear phosphoprotein that plays a role in cell cycle progression, apoptosis and cellular transformation. It functions as a transcription factor that regulates transcription of specific target genes. Mutations, overexpression, rearrangement and translocation of this gene have been associated with a variety of hematopoietic tumors, leukemias and lymphomas, including Burkitt lymphoma. There is evidence to show that alternative translation initiations from an upstream, in-frame non-AUG (CUG) and a downstream AUG start site result in the production of two isoforms with distinct N-termini. The synthesis of non-AUG initiated protein is suppressed in Burkitt's lymphomas, suggesting its importance in the normal function of this gene. The Myc may have an amino acid sequence of SEQ ID NO: 92. The Myc gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 92.

[0135] Abl (abetalipoproteinemia) protein is the large subunit of the heterodimeric microsomal triglyceride transfer protein. Protein disulfide isomerase (PDI) completes the heterodimeric microsomal triglyceride transfer protein, which has been shown to play a central role in lipoprotein assembly. Mutations in MTP can cause abetalipoproteinemia. The abl may have an amino acid sequence of SEQ ID NO: 93. The abl gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 93.

[0136] ErbB1 (epidermal growth factor receptor; EGFR) is a transmembrane glycoprotein that is a member of the protein kinase superfamily. This protein is a receptor for members of the epidermal growth factor family. EGFR is a cell surface protein that binds to epidermal growth factor. Binding of the protein to a ligand induces receptor dimerization and tyrosine autophosphorylation and leads to cell proliferation. Mutations in this gene are associated with lung cancer. The erbB 1 may have an amino acid sequence of SEQ ID NO: 94 (isoform a precursor), SEQ ID NO: 95 (isoform d precursor) or SEQ ID NO: 96 (isoform b precursor). The erbB1 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 94, 95 or 96.

[0137] APIP is an APAF1 (MIM 602233)-interacting protein that acts as a negative regulator of ischemic/hypoxic injury. The APIP may have an amino acid sequence of SEQ ID NO: 97. The APIP gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 97.

[0138] WISP1 (WNT1-inducible signaling pathway protein 1) is a member of the WNT1 inducible signaling pathway (WISP) protein subfamily, which belongs to the connective tissue growth factor (CTGF) family. WNT1 is a member of a family of cysteine-rich, glycosylated signaling proteins that mediate diverse developmental processes. The CTGF family members are characterized by four conserved cysteine-rich domains: insulin-like growth factor-binding domain, von Willebrand factor type C module, thrombospondin domain and C-terminal cystine knot-like domain. This gene may be downstream in the WNT1 signaling pathway that is relevant to malignant transformation. It is expressed at a high level in fibroblast cells, and overexpressed in colon tumors. The encoded protein binds to decorin and biglycan, two members of a family of small leucine-rich proteoglycans present in the extracellular matrix of connective tissue, and possibly prevents the inhibitory activity of decorin and biglycan in tumor cell proliferation. It also attenuates p53-mediated apoptosis in response to DNA damage through activation of the Akt kinase. It is 83% identical to the mouse protein at the amino acid level. Alternative splicing of this gene generates 2 transcript variants. The WISP1 may have an amino acid sequence of SEQ ID NO: 98 (isoform 1 precursor) or SEQ ID NO: 99 (isoform 2 precursor). The WISPI gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 98 or 99.

[0139] WNT1 (wingless-type MMTV integration site family, member 1) may have an amino acid sequence of SEQ ID NO: 100. The WNT1 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 100. The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. it is very conserved in evolution, and the protein encoded by this gene is known to be 98% identical to the mouse Wnt1 protein at the amino acid level. The studies in mouse indicate that the Wnt1 protein functions in the induction of the mesencephalon and cerebellum. This gene was originally considered as a candidate gene for Joubert syndrome, an autosomal recessive disorder with cerebellar hypoplasia as a leading feature. However, further studies suggested that the gene mutations might not have a significant role in Joubert syndrome. This gene is clustered with another family member, WNT10B, in the chromosome 12q13 region.

[0140] RAF1 (v-raf-1 murine leukemia viral oncogene homolog 1) is the cellular homolog of viral raf gene (v-raf). The protein is a MAP kinase kinase kinase (MAP3K), which functions downstream of the Ras family of membrane associated GTPases to which it binds directly. Once activated, the cellular RAF1 protein can phosphorylate to activate the dual specificity protein kinases MEK1 and MEK2, which in turn phosphorylate to activate the serine/threonine specific protein kinases, ERK1 and ERK2. Activated ERKs are pleiotropic effectors of cell physiology and play an important role in the control of gene expression involved in the cell division cycle, apoptosis, cell differentiation and cell migration. Mutations in this gene are associated with Noonan syndrome 5 and LEOPARD syndrome 2. Raf1 may have an amino acid sequence of SEQ ID NO: 101. The RAF1 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 101.

[0141] Src (v-src avian sarcoma (SCHMIDT-RUPPIN A-2) viral oncogene) gene is highly similar to the v-src gene of Rous sarcoma virus. This proto-oncogene may play a role in the regulation of embryonic development and cell growth. The protein encoded by this gene is a tyrosine-protein kinase whose activity can be inhibited by phosphorylation by c-SRC kinase. Mutations in this gene could be involved in the malignant progression of colon cancer. Two transcript variants encoding the same protein have been found for this gene. SRC protein may have an amino acid sequence of SEQ ID NO: 102. The SRC gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 102.

[0142] Akt1 (v-ark murine thymoma viral oncogene homolog 1) protein may have an amino acid sequence of SEQ ID NO: 103. The Akt1 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 103. The serine-threonine protein kinase encoded by the AKT1 gene is catalytically inactive in serum-starved primary and immortalized fibroblasts. AKT1 and the related AKT2 are activated by platelet-derived growth factor. The activation is rapid and specific, and it is abrogated by mutations in the pleckstrin homology domain of AKT1. It was shown that the activation occurs through phosphatidylinositol 3-kinase. In the developing nervous system AKT is a critical mediator of growth factor-induced neuronal survival. Survival factors can suppress apoptosis in a transcription-independent manner by activating the serine/threonine kinase AKT1, which then phosphorylates and inactivates components of the apoptotic machinery. Multiple alternatively spliced transcript variants have been found for this gene.

[0143] Erk1 (extracellular signal-regulated kinase 1; mitogen-activated protein kinase 3; MAPK3) protein is a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act in a signaling cascade that regulates various cellular processes such as proliferation, differentiation, and cell cycle progression in response to a variety of extracellular signals. This kinase is activated by upstream kinases, resulting in its translocation to the nucleus where it phosphorylates nuclear targets. Alternatively spliced transcript variants encoding different protein isoforms have been described. Erk1 protein may have an amino acid sequence of SEQ ID NO: 104. The erk1 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 104.

[0144] Erk2 (mitogen-activated protein kinase 1; MAPK1) protein is a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. The activation of this kinase requires its phosphorylation by upstream kinases. Upon activation, this kinase translocates to the nucleus of the stimulated cells, where it phosphorylates nuclear targets. Two alternatively spliced transcript variants encoding the same protein, but differing in the UTRs, have been reported for this gene. Erk2 protein may have an amino acid sequence of SEQ ID NO: 105. The erk2 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 105.

[0145] BCL2 (B-cell CLL/lymphoma 2) gene encodes an integral outer mitochondrial membrane protein that blocks the apoptotic death of some cells such as lymphocytes. Constitutive expression of BCL2, such as in the case of translocation of BCL2 to Ig heavy chain locus, is thought to be the cause of follicular lymphoma. Two transcript variants, produced by alternate splicing, differ in their C-terminal ends. Bcl2 protein may have an amino acid sequence of SEQ ID NO: 106. The Bcl2 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 106.

[0146] Further, the UCB-MSC may be for example, an UCB-MSC that an oncolytic virus is introduced thereinto. The oncolytic virus may be a gene selected from Herpes simplex virus and Reovirus type 3.

[0147] In the method, the gene introduced in the UCB-MSC may be in an expressionable state. The UCB-MSCs to which a desired gene is introduced in an expressionable state can be appropriately manufactured using techniques that are known in the art. For example, a vector including a desired gene is prepared (see Dehari H et al., Cancer Gene Ther., 10, 75-85, 2003; WO07/037,653) and then the vector can be transduced ex vivo into primary culture MSCs. In this regard, examples of the vector include adenovirus vector, retrovirus vector, adeno-associated virus vector, herpes simplex virus vector, SV40 vector, poliomavirus vector, papillomavirus vector, picarnovirus vector, vaccinia virus vector, and lentivirus vector. For example, a method developed by Tsuda H et al. can be used (Mol Ther 2003, 7, 354-365). Specifically, one day before being infected with an adenovirus gene, MSCs for example, 5.times.10.sup.5 cells may be inoculated into a culture dish. Then the MSCs and a solution including an adenovirus vector to which the adenovirus gene is introduced are incubated at 37.degree. C. in a 5% CO.sub.2 incubator for 1 hour, so that the MSCs are infected with the adenovirus gene. Then the infected MSCs are washed with a phosphoric acid buffer solution and then a conventional medium is applied thereto. Alternatively, without use of a virus vector, a desired gene can be introduced into UCB-MSCs by using a naked DNA and any method selected from a calcium-phosphate method, a cationic liposome method, and an electrophoration method. Alternatively, a fusion protein gene of protein transduction domain (PTD) and anti-tumor protein can be introduced to UCB-MSCs using the fusion protein gene-including vector (see Wu S P et al. Biochem Biophys Res Commun. 346(1), 1-6, 2006).

[0148] The vectors may further include a gene marker for an additional histological examination. The gene marker may be, for example, a gene for coding a chromogenic or fluorescent protein, such as lacZ or a green fluorescent protein (GFP), but is not limited thereto (see Yip S et al., The Cancer J. 9(3), 189-204, 2003).

[0149] In the method, a cell of the tumor may be a cell expressing at least one gene selected from a group of a gene encoding IL-8, a gene encoding GRO-.alpha. and a combination thereof. The tumor may be for example, a tumor selected from the group consisting of a brain tumor, a liver hepatoma, a breast cancer, a colon cancer, a B-cell neoplasm and a combination thereof.

[0150] The brain tumor may be a primary brain tumor or secondary brain tumor. The brain tumor may be for example, a tumor selected from the group consisting of astrocytoma, pilocytic astrocytoma, low-grade astrocytoma, anaplastic astrocytoma, glioblastoma multiforme, brain stem cell glioma, ependymoma, subependymoma, ganglioneuroma, mixed glioma, oligodendroglioma, optic nerve glioma, acoustic neuroma, chordoma, CNS lymphoma, craniopharyngioma, hemangioblastoma, medulloblastoma, meningioma, pineal tumors, pituitary tumors, primitive neuroectodermal tumors, rhabdoid tumors, schwannoma, cysts, neurofibromatosis, pseudotumor cerebri, tuberous sclerosis and a combination thereof. The B-cell neoplasm cell may be for example, a cell selected from the group consisting of a common B acute lymphoblastic leukemia cell, a precursor B acute lymphoblastic leukemia cell, a B-cell chronic lymphocytic leukemia cell, a mantle cell lymphoma cell, a Burkitt's lymphoma cell, a Follicular lymphoma cell and a combination thereof.

[0151] In the method, the subject may an animal. The animal may a mammal, for example, a human.

[0152] In the method, the method may further comprise enhancing the gene selected from the group consisting of a gene encoding IL-8 receptor and a gene encoding GRO-.alpha. receptor at the UCB-MSC. The enhancement of the expression may be achieved by at least one selected from the group consisting of activating the endogenous gene, introducing an exogenous gene and a combination thereof. The introduction of a foreign gene into the UCB-MSC may be made by a known method in the art. The enhancement of the expression level of an endogenous gene, for example, achieved by amplifying the number of the endogenous gene or upregulating the expression of the endogenous gene by using any known method in the art.

[0153] The IL-8 protein is a member of the CXC chemokine family. This chemokine is one of the major mediators of the inflammatory response. This chemokine is secreted by several cell types. It functions as a chemoattractant, and is also a potent angiogenic factor. This gene is believed to play a role in the pathogenesis of bronchiolitis, a common respiratory tract disease caused by viral infection. This gene and other ten members of the CXC chemokine gene family form a chemokine gene cluster in a regionmapped to chromosome 4q. The IL-8 protein may have an amino acid sequence of SEQ ID NO: 107. The IL-8 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 107.

[0154] Chemokine (C-X-C motif) ligand 1 (CXCL1) is a small cytokine belonging to the CXC chemokine family that was previously called GRO1 oncogene, GRO.alpha., KC, Neutrophil-activating protein 3 (NAP-3) and melanoma growth stimulating activity, alpha (MSGA-.alpha.). In humans, this protein is encoded by CXCL1 gene. CXCL1 is secreted by human melanoma cells, has mitogenic properties and is implicated in melanoma pathogenesis. CXCL1 is expressed by macrophages, neutrophils and epithelial cells, and has neutrophil chemoattractant activity. CXCL1 plays a role in spinal cord development by inhibiting the migration of oligodendrocyte precursors and is involved in the processes of angiogenesis, inflammation, wound healing, and tumorigenesis. This chemokine elicits its effects by signaling through the chemokine receptor CXCR2. The gene for CXCL1 is located on human chromosome 4 amongst genes for other CXC chemokines. An initial study in mice showed evidence that CXCL1 decreased the severity of multiple sclerosis and may offer a neuro-protective function. The GRO.alpha. protein may have an amino acid sequence of SEQ ID NO:108. The GRO.alpha. gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO:108.

[0155] The IL-8 receptor may be for example, a receptor selected from a group consisting of CXCR1 and CXCR2. The GRO-.alpha. receptor may be a CXCR2.

[0156] The CXCR1 protein is a member of the G-protein-coupled receptor family. This protein is a receptor for interleukin-8 (IL-8). It binds to IL-8 with high affinity, and transduces the signal through a G-protein activated second messenger system. Knockout studies in mice suggested that this protein inhibits embryonic oligodendrocyte precursor migration in developing spinal cord. This gene, IL8RB, a gene encoding another high affinity IL-8 receptor, as well as IL8RBP, a pseudogene of IL8RB, form a gene cluster in a region mapped to chromosome 2q33-q36. The CXCR1 protein may have an amino acid sequence of SEQ ID NO: 109. The CXCR1 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 109.

[0157] The protein encoded by this gene is a member of the G-protein coupled receptor family. This protein is a receptor for interleukin-8 (IL-8). It binds to IL-8 with high affinity, and transduces the signal through a G-protein activated second messenger system. This receptor also binds to chemokine (C-X-C motif) ligand 1 (CXCL1/MGSA), a protein with melanoma growth stimulating activity, and has been shown to be a major component required for serum-dependent melanoma cell growth. In addition, it binds ligands CXCL2, CXCL3, and CXCL5. This receptor mediates neutrophil migration to sites of inflammation. The angiogenic effects of IL-8 in intestinal microvascular endothelial cells are found to be mediated by this receptor. Knockout studies in mice suggested that this receptor controls the positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration. This gene, IL8RA, a gene encoding another high affinity IL-8 receptor, as well as IL8RBP, a pseudogene of IL8RB, form a gene cluster in a region mapped to chromosome 2q33-q36. The CXCR2 protein may have an amino acid sequence of SEQ ID NO: 110. The CXCR2 gene may have a nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 110.

[0158] In the method, the term "an effective dose" refers to that amount which provides a preventative or therapeutic effect for a tumor condition and administration regimen without causing serious toxic effects in the subject treated. The effective dose may be determined by a person having an ordinary skill in the art. For example, the effective dose may be 1.times.10.sup.4 to 1.times.10.sup.7 cells/kg body weight, preferably 5.times.10.sup.5 to 5.times.10.sup.6 cells/kg body weight.

[0159] Another aspect of the present invention provides a kit for identifying the location and the size of a brain tumor, comprising UCB-MSC, said UCB-MSC being labeled with a detectable marker. The UCB-MSC and a brain tumor may be an UCB-MSC and a brain tumor as described above in this specification, respectively. The detectable marker may be any marker capable of producing a detectable signal. The UCB-MSCs labeled with the detectable marker can be visualized by a state-of-the-art technique, and can be tracked in real time in a live animal. For example, the detectable marker may a marker selected from luciferase-containing enzyme-based fluorescent detector and Tat peptide-derivatized magnetic nanoparticles (Yip S et al., The Cancer J. 9(3), 189-204, 2003). If a stem cell expressing luciferase is used, the administered stem cell migrating to the site of disease can be tracked by identifying bioluminescence in real time and thus, diseases can be diagnosed and the site of disease can be identified (see Weissleder R et al., Nat Med 9, 123-128, 2003). The bioluminescence using luciferase may containing administering a luciferin, a substrate of luciferase to the subject. Tat peptide-derivatized magnetic nanoparticles are connected to UCB-MSCs using a method developed by Lewin et al. (see Nat Biotech 18, 410-414, 2000) and then administered in vivo. The administered UCB-MSCs can be tracked by magnetic resonance imaging (MRI) to the nanoparticles. Accordingly, UCB-MSCs labeled with the Tat peptide-derivatized magnetic nanoparticles can be administered in vivo and then, by identifying a location where UCB-MSCs gather, the tumor and the site of the tumor can be identified. In addition, UCB-MSCs labeled with the marker can be administered during the brain tumor treatment or after the brain tumor treatment to identify the location and size of the distribution of the administered UCB-MSCs.

[0160] Another aspect of the present invention provides a method of identifying the location and the size of a brain tumor of a subject, wherein the method comprises:

(a) administering to the subject an UCB-MSC; (b) identifying the location and the size of the distribution of the administered UCB-MSC.

[0161] In the method of another aspect of the present invention, the method includes administering to the subject an UCB-MSC.

[0162] The administration may be made by using any known method in the art. For example, the administration may be made by a parenteral administration. The parenteral administration includes an injection. The injection may be made intravascullary, intramuscularly, subcutaneously, intradermally, or intrathecally. The administration may be made systemically or locally. The local administration may include direct administration to the tumor tissue.

[0163] The subject may an animal. The animal may a mammal, for example, a human. The UCB-MSC may be an UCB-MSC as described herein above. The UCB-MSC may be labeled with a detectable marker and detected as described herein above.

[0164] In the method of another aspect of the present invention, the method includes identifying the location and the size of the distribution of the administered UCB-MSC.

[0165] The identification of the location and the size of the distribution of the administered UCB-MSC may be made by detecting or measuring the signal from the administered UCB-MSC. The signal may be a signal derived from the detectable marker labeled. The signal may be a light or electrical signal. The light signal may include a visible light, UV or infrared light. The detection or measurement may be made by any known method for example, microscope observation, visual observation, or electronic or electrical detection.

[0166] Another aspect of the present invention provides a method of monitoring a progression of a tumor treatment in a subject who is received the brain tumor treatment, wherein the method comprises: [0167] (a) first administering to the subject an UCB-MSC; [0168] (b) identifying the location and the size of the distribution of the first administered UCB-MSC in the subject; [0169] (c) second administering to the subject an UCB-MSC; [0170] (d) identifying the location and the size of the distribution of the second administered UCB-MSC in the subject; [0171] (e) comparing the location and the size of the distribution identified by (b) and (d), [0172] wherein the subject receives a treatment of the tumor during the period starting from the first administration of the UCB-MSC to the second administration of the UCB-MSC.

[0173] In the method of another aspect of the present invention, the method includes first administering to the subject UCB-MSC. The administration may be made by using any known method in the art as described herein above. For example, the administration may be made by a parenteral administration. The parenteral administration includes an injection. The injection may be made intravascullary, intramuscularly, subcutaneously, intradermally, or intrathecally. The administration may be made systemically or locally. The local administration may include direct administration to the tumor tissue. The UCB-MSC may be an UCB-MSC as described in herein above. The UCB-MSC are labeled with a detectable marker and detected as described herein above. The detectable marker may be any marker capable of producing a detectable signal. For example, the detectable marker may be a marker selected from luciferase-containing enzyme-based fluorescent detector and Tat peptide-derivatized magnetic nanoparticles (Yip S et al., The Cancer J. 9(3), 189-204, 2003). The subject may be an animal. The animal may be a mammal, for example, a human.

[0174] to The method further includes identifying in the subject. The identification of the location and the size of the distribution of the first administered UCB-MSC may be made as described in the above in this specification.

[0175] The method further includes second administering to the subject UCB-MSC. The administration, the subject and UCB-MSC may be the same as described in the above in this specification. The first UCB-MSC and second UCB-MSC may be derived from the same or different sources of umbilical cords bloods. The second may be made in the same way or different way as the first administration.

[0176] The method further includes identifying the location and the size of the distribution of the second administered UCB-MSC in the subject. The identification of the location and the size of the distribution of the first administered UCB-MSC may be made as described in the above in this specification.

[0177] The method further includes comparing the location and the size of the distribution identified by (b) and (d). The comparison may be made for example, by visually comparing the visual data by (b) and (d) or by comparing the digital data by (b) and (d), respectively.

[0178] In the method, the treatment of the tumor may be any cancer therapy. The treatment may include for example, a treatment selected from the group consisting of chemotherapy, radiotherapy, surgery and a combination thereof.

[0179] In the method, if the identified location and the size of the distribution of the second administered UCB-MSC in the subject is smaller than that of the first administered UCB-MSC, the progression of the treatment may be determined as successful, or if the identified location and the size of the distribution of the second administered UCB-MSC in the subject is same or larger than that of the first administered UCB-MSC, the progression of the treatment may be determined as not successful.

[0180] Another aspect of the present invention provides a method for delivering a therapeutic gene to a site of a subject, the site comprising cells expressing at least one selected from the group consisting of IL-8 and GRO-.alpha. and inducing tropism of UCB-MSC toward the cells, wherein the method comprises the step of administering to the subject an effective dose of the UCB-MSC.

[0181] The method includes the step of administering to the subject an effective dose of the to UCB-MSC. The administration, the subject and the UCB-MSC are as described in the above in this specification. The term "an effective dose" refers to that amount which delivers a therapeutic gene to a site of a subject comprising cells expressing at least one selected from the group consisting of IL-8 and GRO-.alpha. and inducing tropism of UCB-MSC toward the cells without causing serious toxic effects in the subject treated. The effective dose may be determined by a person having an ordinary skill in the art. For example, the effective dose may be 1.times.10.sup.4-1.times.10.sup.7 cells/kg body weight.

[0182] The UCB-MSC may be an UCB-MSC which a therapeutic gene is introduced into the UCB-MSC. The therapeutic gene may be for example, a gene selected from the group consisting of a tumor suppressor gene, an apoptosis-inducing factor gene, a cell cycle regulatory gene and an angiogenesis inhibitor gene. Further, The UCB-MSC may be for example, an UCB-MSC that a prodrug converting enzyme gene is introduced to the UCB-MSC. The tumor suppressor gene, an apoptosis-inducing factor gene, a cell cycle regulatory gene, an angiogenesis inhibitor gene and prodrug converting enzyme gene may be the same as described in the above in this specification.

[0183] In the method of another aspect of the present invention, the method may further comprise administering a prodrug of an anticancer drug into the subject. The prodrug may be for example, 5-fluorocytosine (5-FC), which is a prodrug of 5-fluorouracil (5-FU). The administration and the subject may be as described in the above in this specification.

[0184] The UCB-MSC may be for example, an UCB-MSC an antisense or siRNA of a gene related to brain tumor is introduced thereinto. The gene related to brain tumor may be a gene selected from the group consisting of a gene encoding a Ras family protein, a gene encoding c-myc, a gene encoding abl, a gene encoding erbB-1, a gene encoding EGFR, a gene encoding Bax, a gene encoding Apaf-1 interacting protein (APIP), a gene encoding Wnt-1-induced secreted protein 1 (WISP-1), a gene encoding Wnt, a gene encoding Raf-1, a gene encoding Src, a gene encoding Akt, a gene encoding Erk-1,2 and a gene encoding BcL-2.

[0185] Further, the UCB-MSC may be for example, an UCB-MSC an oncolytic virus is introduced thereinto. The oncolytic virus may be a gene selected from Herpes simplex virus and Reovirus type 3.

[0186] In the method of the aspect of the present invention, the brain tumor may be for example, a tumor selected from the group consisting of astrocytoma, pilocytic astrocytoma, low-grade astrocytoma, anaplastic astrocytoma, glioblastoma multiforme, brain stem cell glioma, ependymoma, subependymoma, ganglioneuroma, mixed glioma, oligodendroglioma, optic nerve glioma, acoustic neuroma, chordoma, CNS lymphoma, craniopharyngioma, hemangioblastoma, medulloblastoma, meningioma, pineal tumors, pituitary tumors, primitive neuroectodermal tumors, rhabdoid tumors, schwannoma, cysts, neurofibromatosis, pseudotumor cerebri and tuberous sclerosis.

[0187] In the method of the aspect of the present invention, the subject may an animal. The animal may be a mammal, for example, a human.

[0188] In the method, the cell expressing at least one selected from the group consisting of IL-8 and GRO-.alpha. and inducing tropism of UCB-MSC toward the cells may be for example, a cell selected from the group consisting of a brain tumor cell, a hepatoma cell, a breast cancer cell, a lung cell with an acute respiratory distress syndrome, a colon cancer cell, a B-cell neoplasm cell and a combination thereof.

[0189] The brain tumor may be for example, a tumor selected from the group consisting of astrocytoma, pilocytic astrocytoma, low-grade astrocytoma, anaplastic astrocytoma, glioblastoma multiforme, brain stem cell glioma, ependymoma, subependymoma, ganglioneuroma, mixed glioma, oligodendroglioma, optic nerve glioma, acoustic neuroma, chordoma, CNS lymphoma, craniopharyngioma, hemangioblastoma, medulloblastoma, meningioma, pineal tumors, pituitary tumors, primitive neuroectodermal tumors, rhabdoid tumors, schwannoma, cysts, neurofibromatosis, pseudotumor cerebri and tuberous sclerosis. The B-cell neoplasm cell may be for example, a cell selected from the group consisting of a common B acute lymphoblastic leukemia cell, a precursor B acute lymphoblastic leukemia cell, a B-cell chronic lymphocytic leukemia cell, a mantle cell lymphoma cell, a Burkitt's lymphoma cell, a Follicular lymphoma cell and a combination thereof.

[0190] Another aspect of the present invention provides a kit for identifying the location and the size of a site of a subject, the site comprising cells expressing at least one selected from the group consisting of IL-8 and GRO-.alpha. and inducing tropism of UCB-MSC toward the cells, wherein the kit comprises UCB-MSC, the UCB-MSC are labeled with a detectable marker. The UCB-MSC and the detectable marker are as described in the above in this specification. The labeled UCB-MSC may be detected as described in the above in this specification. The marker may be located within nucleoplasm, within cytoplasm, within a cellular organelle or on or within the cell membrane.

[0191] In the kit, the cells expressing at least one selected from the group consisting of IL-8 and GRO-.alpha. and inducing tropism of UCB-MSC toward the cells may be for example, a cell selected from the group consisting of a brain tumor cell, a hepatoma cell, a breast cancer cell, a lung cell with an acute respiratory distress syndrome, a colon cancer cell, a B-cell neoplasm cell and a combination thereof.

[0192] The brain tumor may be for example, a tumor selected from the group consisting of astrocytoma, pilocytic astrocytoma, low-grade astrocytoma, anaplastic astrocytoma, glioblastoma multiforme, brain stem cell glioma, ependymoma, subependymoma, ganglioneuroma, mixed glioma, oligodendroglioma, optic nerve glioma, acoustic neuroma, chordoma, CNS lymphoma, craniopharyngioma, hemangioblastoma, medulloblastoma, meningioma, pineal tumors, pituitary tumors, primitive neuroectodermal tumors, rhabdoid tumors, schwannoma, cysts, neurofibromatosis, pseudotumor cerebri and tuberous sclerosis. The B-cell neoplasm cell may be for example, a cell selected from the group consisting of a common B acute lymphoblastic leukemia cell, a precursor B acute lymphoblastic leukemia cell, a B-cell chronic lymphocytic leukemia cell, a mantle cell lymphoma cell, a Burkitt's lymphoma cell and a Follicular lymphoma cell.

[0193] Another aspect of the present invention provides a method of identifying the location and the size of a site of a subject, the site comprising cells expressing at least one selected from the group consisting of IL-8 and GRO-.alpha. and inducing tropism of UCB-MSC toward the cells, wherein the method comprises:

[0194] (a) administering to the subject an UCB-MSC;

[0195] (b) identifying the location and the size of the distribution of the administered UCB-MSC.

[0196] The method includes administering to the subject an UCB-MSC. The administration, the subject and the UCB-MSC may be the same as described in the above in this specification. The UCB-MSC may be labeled with a detectable marker and detected as described in above in this specification. The marker may be located within nucleoplasm, within cytoplasm, within a cellular organelle or on or within the cell membrane.

[0197] The cell expressing at least one selected from the group consisting of IL-8 and GRO-.alpha. and inducing tropism of UCB-MSC toward the cell may be for example a cell selected from the group consisting of a brain tumor cell, a hepatoma cell, a breast cancer cell, a lung cell with an acute respiratory distress syndrome, a colon cancer cell and a B-cell neoplasm cell. The brain tumor and B-cell neoplasm cell are the same as described in the above in this specification.

[0198] Another aspect of the present invention provides a method of monitoring treatment progression of a disease occurred in a site of a subject, the site comprising cells expressing at least one selected from groups consisting of IL-8 and GRO-.alpha. and inducing tropism of UCB-MSC, wherein the method comprises: [0199] (a) first administering to the subject an UCB-MSC; [0200] (b) identifying the location and the size of the distribution of the first administered UCB-MSC in the subject; [0201] (c) second administering to the subject an UCB-MSC; [0202] (d) identifying the location and the size of the distribution of the second administered UCB-MSC in the subject; and [0203] (e) comparing the location and the size of the distribution identified by (b) and (d), wherein the subject receives a treatment of the disease during the period starting from the first administration of the UCB-MSC to the second administration of the UCB-MSC.

[0204] In the method of another aspect of the present invention, the method includes first administering to the subject an UCB-MSC. The administration, the subject and the UCB-MSC may be the same described in the above in this specification. The UCB-MSC are labeled with a detectable marker and detected as described in the above in this specification.

[0205] The method further includes identifying the location and the size of the distribution of the first administered UCB-MSC in the subject. The identification of the location and the size of the distribution of the first administered UCB-MSC may be made as described in the above in this specification.

[0206] The method further includes second administering to the subject UCB-MSC. The administration, the subject and UCB-MSC may be the same as described in the above in this specification. The first UCB-MSC and second UCB-MSC may be derived from the same or different sources of umbilical cord bloods. The second administration may be made in the same way or different way as the first administration. The second UCB-MSC may be labeled with a detectable marker. The detectable marker is as described in the above. The detectable marker used in the second UCB-MSC may be the same with or different from that used in the first UCB-MSC.

[0207] The method further includes identifying the location and the size of the distribution of the second administered UCB-MSC in the subject. The identification of the location and the size of the distribution of the first administered UCB-MSC may be made as described in the above in this specification.

[0208] The method further includes comparing the location and the size of the distribution identified by (b) and (d). The comparison may be made for example, by visually comparing the visual data from (b) and (d) or by comparing the digital data from (b) and (d), respectively.

[0209] In the method, the disease may be any disease caused by cells expressing, for example, overexpressing at least one selected from groups consisting of IL-8 and GRO-.alpha. and inducing tropism of UCB-MSC.

[0210] The treatment of the disease may be any cancer therapy. The treatment may include for example, a treatment selected from the group consisting of chemotherapy, radiotherapy, surgery and a combination thereof.

[0211] In the method, if the identified location and the size of the distribution of the second administered UCB-MSC in the subject is smaller than that of the first administered UCB-MSC, the progression of the treatment may be determined as successful, or if the identified location and the size of the distribution of the second administered UCB-MSC in the subject is the same or larger than that of the first administered UCB-MSC, the progression of the treatment may be determined as not successful.

[0212] In the method, the cell expressing at least one selected from the group consisting of IL-8 and GRO-.alpha. and inducing tropism of UCB-MSC toward the cell may be for example, a cell selected from the group consisting of a brain tumor cell, a hepatoma cell, a breast cancer cell, a lung cell with an acute respiratory distress syndrome, a colon cancer cell and a B-cell neoplasm cell. The B-cell neoplasm cell may be for example a cell selected from the group consisting of a common B acute lymphoblastic leukemia cell, a precursor B acute lymphoblastic leukemia cell, a B-cell chronic lymphocytic leukemia cell, a mantle cell lymphoma cell, a Burkitt's lymphoma cell and a Follicular lymphoma cell.

[0213] Another aspect of the present invention provides a method of delivering an anti-tumor agent to a site of a tumor in a subject, which comprises administering mesenchymal stem cells together with the anti-tumor agent to the site, wherein the mesenchymal stem cells (MSCs) are umbilical cord blood-derived MSCs ("UCB-MSC").

[0214] The administration and UCB-MSC may be as described in the above in this specification. The MSCs may be used in an amount of 1.times.10.sup.4-1.times.10.sup.7 cells/kg body weight. The anti-tumor agent may be any anti-tumor agent known in the art. The anti-tumor agent may be an agent selected from the group consisting of a tumor suppressor gene, an apoptosis-inducing factor gene, a cell cycle regulatory factor gene and an angiogenesis inhibitor gene. The anti-tumor agent may be admixed with the UCB-MSCs or be carried within the UCB-MSCs. The anti-tumor agent may be introduced into the UCB-MSCs by using any known introduction method of a foreign nucleic acid in the art. The introduction method may be for example, electroporation, transformation, transfection and bombardment.

[0215] In the method, the tumor may be a brain tumor. The brain tumor may be a tumor selected from the group consisting of astrocytoma, pilocytic astrocytoma, low-grade astrocytoma, anaplastic astrocytoma, glioblastoma multiforme, brain stem glioma, ependymoma, subependymoma, ganglioneuroma, mixed glioma, oligodendroglioma, optic nerve glioma, acoustic neuroma, chordoma, CNS lymphoma, craniopharyngioma, hemangioblastoma, medulloblastoma, meningioma, pineal tumors, pituitary tumors, primitive neuroectodermal tumors, rhabdoid tumors, schwannoma, cysts, neurofibromatosis, pseudotumor cerebri, tuberous sclerosis and a combination thereof.

[0216] The tumor suppressor gene may be a gene selected from the group consisting of phosphatase and tensin homolog gene (PTEN), Maspin gene, RUNX3 gene, Caveolin-1 gene, nm23 gene, Rb protein gene, Brush-1 gene, a gene encoding an inhibitor of tumor growth (ING-4), surviving gene, X chromosome linked inhibitor apoptosis protein (XIAP) gene, neural apoptosis inhibitory protein (NAIP) gene and genes encoding a protein related to regulating said genes. The apoptosis inducing factor gene may be a gene selected from the group consisting of a gene encoding cytokine, a gene encoding interleukin, a gene encoding a tumor necrosis factor (TNF), a gene encoding interferon (INF-.alpha., INF-.beta., INF-.gamma.), a gene encoding a colony stimulating factor (CSFs), a gene encoding p53, a gene encoding Apaf-1, a gene encoding TRAIL, a gene encoding Caspase, a gene encoding Bax, a gene encoding Bad, a gene encoding FADD, a gene encoding INK, a gene encoding p38 kinase and genes encoding proteins related to regulating said genes. The cell cycle regulatory factor gene may be a gene selected from the group consisting of a gene encoding cdc2, a gene encoding Cyclin (Cyclin A, Cyclin D, Cyclin E), a gene encoding cdc25C, a gene encoding WAF, a gene encoding INK4, a gene encoding CDK (CDK1, CDK2, CDK4, CDK6), a gene encoding Rb protein, a gene encoding E2F, an antisense or siRNA thereof and genes encoding proteins related to regulating said genes. The angiogenesis inhibitor gene may be a gene selected from the group consisting of a gene encoding thrombospondin-1, a gene encoding endostatin, a gene encoding tumstatin, a gene encoding canstatin, a gene encoding vastatin, a gene encoding restin, a gene encoding a vascular endothelial growth factor inhibitor, a gene encoding maspin, a gene encoding angiopoietins, a gene encoding 16-kd prolactin fragment and a gene encoding endorepellin.

[0217] Further, the anti-tumor agent may be a prodrug converting enzyme gene.

[0218] Further, the anti-tumor agent may be for example, an antisense or siRNA of a gene related to a brain tumor. The gene related to brain tumor may be for example a gene selected from the group consisting of a gene encoding Ras family, a gene encoding c-myc, a gene encoding abl, a gene encoding erbB-1, a gene encoding EGF-R, a gene encoding Bax, a gene encoding Apaf-1 interacting protein (APIP), a gene encoding Wnt-1-induced secreted protein 1 (WISP-1), a gene encoding Wnt, a gene encoding Raf-1, a gene encoding Src, a gene encoding Akt, a gene encoding Erk-1,2 and a gene encoding BcL-2. The anti-tumor agent may be an oncolytic virus. The oncolytic virus may be a virus selected from Herpes simplex virus and Reovirus type 3.

[0219] In the present specification, the term "umbilical cord blood" refers to blood taken from an umbilical vein connecting a placenta to a fetus in all mammals including humans.

[0220] In the present specification, the term "umbilical cord blood-derived mesenchymal stem cells ("UCB-MSC") as used throughout the application is defined as mesenchymal stem cells that are isolated from UCB, expanded from the MSCs isolated from the UCB, or a mixture thereof, and a culture containing such expanded MSCs". The UCB-MSC may be derived from umbilical cord blood of mammals, preferably humans.

[0221] In the present specification, the term "treatment" refers to preventing disease or disorder development in an animal, preferably a mammal, and more preferably humans which are not yet diagnosed with but susceptible to a disease; suppressing disease progression; and alleviating disease.

[0222] In the present specification, the term "brain tumor" refers to a malignant or benign tumor developing in the brain and the spinal cord and all kinds of tumors developing in a glial cell and a non-glial cell. In this regard, the brain tumor may be a primary brain tumor or a secondary brain tumor.

[0223] Meanwhile, terms which are not defined in the present specification may have meanings which are conventionally defined in the art.

[0224] It is noted that all the prior art referred to in the present specification is incorporated by reference in its entirety.

[0225] The present invention will be described in further detail with reference to the following examples. These examples are for illustrative purposes only and are not intended to limit the scope of the present inventive concept.

EXAMPLES

[0226] U-87 MG, A549, KATO III, PLC/PRF5, LN18, U138 and U251 cell lines were purchased from American Type Culture Collection (ATCC) and used in the present experiments. A549, KATOIII and PLC/PRF5 cells were cultured in RPMI containing 10-20% (v/v) FBS (HyClone, Logan, Utah, US) and Gentamicin at 37.degree. C. in a 5% CO.sub.2 incubator. U-87 MG, LN18, U138 and U251 cells were grown in an Eagle's minimum essential medium (MEM) containing 10-20% (v/v) FBS. Bone marrow-derived mesenchymal stem cell (BM-MSCs) was purchased from LONZA. BM-MSCs and established UCB-MSCs were cultured in .alpha.-MEM media containing 10-20% FBS.

Example 1

Preparation of Umbilical Cord Blood-Derived Mesenchymal Stem Cells (UCB-MSCS)

[0227] UCB samples were collected from the umbilical vein of deliveries, with informed maternal consent. Specifically, a 16-gauge needle of a UCB collection bag containing 44 mL of CPDA-1 anticoagulant (Greencross Co., Yongin, Kyungki-do, Korea) was inserted into the umbilical vein and UCB was collected by gravity. In all cases, UCB harvests were processed within 48 hours of collection, with viability of 90% or more.

Example 2

Isolation and Expansion of UCB-MSCs

[0228] UCB-MSCs prepared according to Example 1 were centrifuged with a Ficoll-Hypaque gradient (produced by Sigma Co., density: 1.077 g/mL), and then washed several times to to remove impurities. 10 to 20% FBS (HyClone Co.)-containing a basic medium (.alpha.-MEM, Gibco BRL Co.) was added to the resultant product to suspend UCB-MSCs. The UCB-MSCs were portioned at a suitable concentration into each of 10 to 20% FBS--containing a basic media, and then cultivated at 37.degree. C. in a 5% CO.sub.2 incubator while the medium was altered twice in a week (FIG. 1). When the cultured cells formed a single layer, MSCs expanding in a spindle shape were identified with a phase-contrast microscope. Then, sub-cultivation was repeatedly performed until the MSCs expanded sufficiently.

Example 3

Preparation of UCB-MSCs Labeled with PKH-26

[0229] UCB-MSCs cultivated according to Example 2 were dyed with PKH-26 (Sigma Co.) using a method disclosed in a reference [Barreda D A et al., Developmental and Comparative Immunology, 24:395-406, 2000]. First, UCB-MSCs were separated from the cell culture dish by using Trypsin and then, 2.times.10.sup.7 cells were washed with an FBS-free medium. The washed cells were collected using a centrifuge and then suspended in 1 mL of Diluent C in a kit provided by a manufacturer. Then the resultant cell suspension solution (2.times.) was mixed with 1 ml of the PKH fluorescent dye solution(2.times.) and then the mixture was reacted at 25.degree. C. for 5 minutes. To terminate the labeling reaction, a medium containing an equal volume of fetal bovine serum (FBS) was added to the reaction product and then left to sit for 1 minute. Cells labeled with PKH26 were collected by centrifuging and then, washed with a 10 to 20% FBS-containing medium three times and used in experiments.

Example 4

Co-Culture of MSCs and Other Cell Lines in Transwell Chamber

[0230] Human UCB-MSCs (hUCB-MSCs) were dyed with PKH-26 (produced by Sigma). The dyed hUCB-MSCs and other tumor cell lines were co-cultured under a culture condition in a transwell chamber (FALCON) (MSC: cancer cell lines=1:5). For a control group, cancer cell lines-free MSCs were cultured in the same condition as described above. The transwell chamber used in the co-culturing, as illustrated in FIG. 2, included a lower compartment and an upper compartment, wherein the lower compartment is separated from the upper compartment by a microporous membrane (8 .mu.m size.) In the upper compartment, PKH26-labeled hUCB-MSCs were cultured; and in lower compartment, each of human brain tumor cell line U-87 MG, human rectal cancer cell line LS174-T, human B lymphocyte NC-37, and mouse's fibroblast NIH3T3 was cultured. After co-culturing for one day, two days, and three days each, the migration of PKH26-labeled UCB-MSCs was identified using a phase-contrast microscope (.times.100) and PKH26-labeled UCB-MSCs migrated was counted (FIG. 3). The same experiment was performed using KATO III, A549, PLC/PRF5, LN18, U138, and U251 which are tumor cell lines and the migration of PKH26-labeled UCB-MSCs was identified. The same experiment was performed in a condition in which a medium conditioned by U-87 MG cells was placed in the lower compartment (FIG. 4).

[0231] That is, PKH26-labeled UCB-MSCs were co-cultured with various tumor cell lines in a transwell chamber and then, PKH-labeled mesenchymal stem cells that have migrated into the lower compartment were counted. As a result, UCB-MSCs had a strong tropism for U-87 MG, LN18, U138, and U251 that are brain tumor cell lines, and a weak tropism for other tumor cells (FIGS. 3 and 4). In B of FIG. 3, the left image shows the case of the control group in which a human cell line-free medium was added instead of tumor cells, and the right image shows the case in which UCB-MSCs were co-cultured with U-87 MG cell. Referring to FIG. 3, the migration of many PKH26-labeled UCB-MSCs was identified. When the human cell line-free medium was used instead of tumor cells and cultured, the migration of PKH26-labeled UCB-MSCs was negligible (see the left image of B of FIG. 3). However, PKH26-labeled UCB-MSCs had a tropism for a conditioned medium that did not contain U-87 MG cells but U-87 MG cells had been cultured therein (see D of FIG. 4). Such results show that the conditioned medium contained soluble factors that function to attract UCB-MSCs toward U-87 MG cells.

Example 5

Comparison of Tropism of BM-MSCs for U-87 MG and Tropism of UCB-MSCs for U-87 MG

[0232] A tropism of BM-MSCs for U-87 MG was compared to a tropism of UCB-MSCs for U-87 MG, using a transwell chamber. U-87 MG cancer cells or medium were placed in a lower compartment, and BM-MSCs and UCB-MSCs each were placed in an upper compartment. In all cases, the culturing was performed for two days. As a result, UCB-MSCs were found to have a stronger tropism for U-87 MG than BM-MSCs (FIG. 5).

Example 6

Comparison of Migrations of MSC

[0233] UCB-MSCs donated from four donors in the upper compartment and each of A549 that is lung cancer cell, HeLa that is cervical cancer cell, and U-87 MG that is brain cancer-glioma cell in the lower compartment were co-cultured in a transwell chamber. Then, chemotactic indices of UCB-MSCs in each case were compared (FIG. 6).

[0234] A549, HeLa, and U-87 MG cells were purchased from American type culture collection (ATCC). Each of A549 and U87 MG cells was cultured in 10-20% bovine serum-containing RPMI1640, and HeLa was cultured in DMEM. In each case, the chemotactic index was calculated by dividing the number of UCB-MSCs migrated toward U87 MG by the number of UCB-MSCs migrated in the control experiment. A tropism of UCB-MSCs for those cancer cells was analyzed. As a result, it was found that UCB-MSCs had the strongest tropism for U-87 MG that is a brain tumor cell line.

Example 7

Cytokine Array

[0235] MSCs and each of three kinds of human cells, including U-87 MG tumor cell, were co-cultured, and the cultured medium was collected. The cytokine profile from the cultured medium was examined by using a cytokine antibody array.

[0236] A film to which antibodies of various cytokine were attached was taken from a kit for a cytokine array purchased from R&D System Co. and was reacted with a blocking solution for one hour. Separately, amounts of the media prepared by co-culturing UCB-MSCs and each of three kinds of human cells, including U-87 MG tumor cell were adjusted to 1.5 mL or less, and each medium was mixed with the mixed antibodies of cyokines contained in the kit and an antigen-antibody reaction was induced for one hour. The medium in which the supplied cytokine antibodies were combined with secreted cytokines was reacted with the film that was subjected to the blocking for 4.degree. C. for 12 hours. After the reaction, the film was placed in a washing solution and washed, and then washed with tertiary distilled water. Then the film was dried at room temperature. After repeating the washing and drying process two or three times, the film was reacted in a solution containing streptavidin-HRP for 30 minutes. Then the film was washed with a washing solution three times, reacted with a chromatic reagent, and then exposed to an X-ray film in the dark room.

[0237] U-87 MG inducing strong tropism of UCB-MSCs secreted growth-related oncogene (GRO-alpha), IL-8, MCP-1, G-CSF, GM-CSF, IL-6, IL-1.beta., a migration inhibitory factor (MIF), and Serpin E1. Specifically the amounts of GRO-alpha and IL-8 were higher than those of MCP-1, G-CSF, GM-CSF, IL-6, IL-1.beta., a MIF, and Serpin E1. FIG. 7 shows results obtained by analyzing cell lysates and cell culture supernatants through a cytokine array. Array results and information about changed spots compared to the control group are shown in FIG. 1. In Table 1, cytokines in parentheses are cytokines that were derived by the co-culturing with tumor cells. It is highly likely that these cytokines may induce a tropism of UCB-MSCs.

TABLE-US-00001 TABLE 1 Cell Lysate Supernatants NC37 MIF+++ MIF+++ sICAM-1++ Serpin E1+++ MIP-1a++ MIP-1a++ IL-16++ MIP-1b++ IL-6+ IL-8+ LS174-T MIF+++ MIF+++ IL-1ra++ Serpin E1+++ GROa+ IL-6+ IL-8+ U87 sICAM-1+++ (GROa+++) IL-6+++ IL-6+++ MIF+++ (IL-8+++) Serpin E1+++ Serpin E1+++ IL-1ra++ (G-CSF++) IL-8++ MIF++ G-CSF++ (MCP-1+) IL-1a+ IL-1b+

[0238] Conditioned media collected from UCB-MSCs cultures only, U-87 MG cell cultures only, and the co-culture of both cells were prepared. Each conditioned medium was incubated on an array membrane, and then visualized by an ECL reagent. Then the visualized conditioned media were compared to each other (see FIG. 8). FIG. 8A shows cytokine antibody array analysis results from the medium prepared by culturing UCB-MSCs only and a control medium. FIG. 8B shows cytokine antibody array analysis results from the medium prepared by culturing the U-87 MG only, and the medium prepared by co-culturing UCB-MSCs and U-87 MG.

[0239] FIG. 8C shows results identified by isolating mRNA from UCB-MSCs cultured with and without U-87 MG (left) or from U-87 MG cultured with and without UCB-MSCs (right). RT-PCR was performed with IL-8 specific primers and GAPDH was used as a control. When the level of IL-8 mRNA was measured by RT-PCR, it was found that U-87 MG expresses IL-8 in both cases which U-87 MG cultured with and without UCB-MSCs.

Example 8

Effect of Cytokine with Respect to UCB-MSCs Migration

[0240] The effect of IL-8, GRO-.alpha., MCP-1 (RND Systems, MN, USA) with respect to migration of UCB-MSCs was measured using transwell migration assay. PHK-26-labelled UCB-MSCs were placed in the upper compartment and no cells were placed in the lower compartment. UCB-MSCs were cultured in an IL-8 free medium or in a medium containing different concentrations of recombinant humane IL-8 for 24 hours. As a result, it can be seen that UCB-MSCs migrated more when treated with IL-8 than when they were not treated with IL-8 (FIG. 9A).

[0241] IL-8 receptor on UCB-MSCs can be effectively blocked by anti-human CXC chemokine receptor 1 (CXCR1) antibodies. After pre-incubation of UCB-MSCs with anti-CXCR1 antibodies, recombinant IL-8 was again applied to UCB-MSCs. IL-8 mediated migration of UCB-MSCs was reduced, in a dose-dependant manner, by anti-CXCR1 treatment (FIG. 9B). Anti-CXCR2 treatment also showed the same effect.

[0242] Similarly, GRO-.alpha. treatment also enhanced UCB-MSCs migration when compared to untreated cells (FIG. 9C). GRO-.alpha. also belongs to the CC subfamily and can interact with the CXCR2 receptor [see Wuyts A. et al. Eur J Biochem 255, 67-73 (1998)].

[0243] In contrast, significant differences were not found in UCB-MSCs migration in cultures treated with MCP-1 (FIG. 9 D). These data strongly indicate that IL-8 and GRO-.alpha. participate in migration of UCB-MSCs towards U-87 MG cells.

Example 9

UCB-MSCs Migrates Toward A549 Cell Overexpressing IL-8

[0244] The relationship between the concentration of IL-8 secreted from several cancer cells and UCB-MSCs migration toward each cancer cell was identified. FIG. 10A shows ELISA results indicating concentrations of IL-8 secreted in media in which U87 MG (brain tumor), KATOIII (gastric cancer), A549 (lung cancer), and PLC/PRF5 (liver cancer) cells were cultured. In this regard, the concentration of IL-8 was measured per 1.times.10.sup.5 cells. Among the cancer cell lines assayed, U-87 MG showed the highest IL-8 production. This data suggested that UCB-MSCs had a strong migration attraction toward IL-8 producing cells. In addition, other human brain to tumor cells, that is, LN18, U138, and U251 cells, also showed the similar concentration level of IL-8 as that of U-87 MG (see FIG. 10B). Therefore, it can be seen that UCB-MSCs has a tropism for IL-8 secreted by brain tumor cells.

[0245] In order to know whether addition of IL-8 to cells expressing a lower level of IL-8 induces the migration of UCB-MSCs, IL-8 was overexpressed in A549 that is a human lung cancer cell. FIG. 10C shows migration results of UCB-MSCs after IL-8 gene was introduced to A549 cells that secrete a low level of IL-8 by using a lipofectamine reagent and then IL-8 was overexpressed. Referring to FIG. 10C, more UCB-MSCs migrated in A549 cells having overexpressed IL-8 than in A549 cells. Accordingly, it can be seen that IL-8 could be a strong inducer of UCB-MSCs migration. FIG. 10D shows the concentration of IL-8 secreted into a medium in a condition of C measured by ELISA.

Example 10

Comparison of Reaction of BM-MSCs and UCB-MSCs with Respect to IL-8

[0246] Since it is known that BM-MSCs migrate toward U-87 MG cells in vitro and in vivo, migration characteristics of BM-MSCs and UCB-MSCs with respect to U-87 MG cells were compared to those with respect to IL-8 (FIG. 11). A of FIG. 11 shows tropism characteristics of BM-MSCs and UCB-MSCs migrated toward the lower compartment B, that is, toward U87 MG. B of FIG. 11 shows tropism characteristics of BM-MSCs and UCB-MSCs migrated toward the lower compartment B when they are treated with IL-8 for 14 hours. Referring to FIG. 11, more UCB-MSCs migrated than BM-MSCs. Therefore, it can be seen that UCB-MSCs strongly corresponded to IL-8 and migrated more, but BM-MSCs relatively weakly corresponded to IL-8.

Example 11

Expression levels of the IL-8 receptor CXCR1 and CXCR2 in UCB-MSCs

[0247] Expression levels of CXCR1 and CXCR2 which are IL-8 receptors in UCB-MSCs and BM-MSCs were compared by measuring mRNA and protein in each of CXCR1 and CXCR2. FIG. 12 A shows results of RT-PCR which was performed with CXCR1 and CXCR2 primers after mRNA was isolated in each of CXCR1 and CXCR2. GAPDH was included into each sample to assess the quantity of the isolated RNA. FIG. 12 B shows results of expression levels of CXCR1 and CXCR2 obtained by measuring each mRNA band intensity of gel obtained from FIG. 12A using a densitometer (* and **, p<0.001; n=4). As a result of RT-PCR analysis for all the RNA isolated from UCB-MSCs and BM-MSCs, the band density of the PCR product of CXCR1 and CXCR2 was higher in UCB-MSCs than in BM-MSCs. FIG. 12 C shows analysis results obtained by immunostaining UCB-MSCs and BM-MSCs with anti-CXCR1 and CXCR2 antibodies to identify expression levels of CXCR1 and CXCR2 (.times.400). Referring to C of FIG. 12, UCB-MSCs and BM-MSCs showed high expression levels of CXCR1 and CXCR2. Since IL-8 has high affinity to CXCR1 and CXCR2, increased UCB-MSCs migration toward U-87 MG may be due to up-regulated expression of CXCR1 and CXCR2. FIG. 12 D shows analysis results obtained by immunostaining UCB-MSCs and BM-MSCs with a secondary antibody only without anti-CXCR1 and CXCR2 antibodies to identify antigen specificity of the anti-CXCR1 and CXCR2 antibodies.

Example 12

Introduction of Gene into Umbilical Cord Blood Mesenchymal Stem Cell

[0248] As an example of an experiment in which a gene is introduced into UCB-MSCs, a green fluorescent protein (GFP) was overexpressed using an electroporation method with a human MSC neucleofector produced by amaxa biosystem Co. and an electroporation method. 4.times.10.sup.5 cells of UCB-MSCs were cultured for two days and then placed in a mixture of 5 mg of a GFP encoding gene and 100 ml of a human MSC nucelofector for 15 minutes and the gene was introduced in an electroporator. The resultant UCB-MSCs was moved to a plate and after 24 hours, expression levels of GFP were identified with a fluorescent microscope. The GFP could be identified in a cytoplasm of each MSC (see FIG. 13).

[0249] To test a tropism of UCB-MSCs to which the GFP encoding gene is introduced, each of a GFP encoding gene and an empty gene was overexpressed in UCB-MSCs and then, a tropism of the resultant UCB-MSCs for U-87 MG was identified. After the gene was introduced as described above, UCB-MSCs expressing GFP were placed in an upper compartment of a transwell chamber and U-87 MG was placed in a lower compartment of the transwell chamber, and then UCB-MSCs expressing GFP and U-87 MG were co-cultured for 24 hours. Among cells migrated toward the lower compartment, GFP positive cells were identified. As a result, it can be seen that UCB-MSCs overexpressing GFP due to introduction of a GFP gene had a strong tropism for U87 MG (FIG. 14).

DESCRIPTION OF THE DRAWINGS

[0250] FIG. 1 is a view illustrating a process of collecting mesenchymal stem cells (MSCs);

[0251] FIG. 2 is a schematic view of a transwell chamber that is used to co-culture umbilical cord blood derived mesenchymal stem cells (UCB-MSCs) and various cell lines according to the present invention;

[0252] FIG. 3 is a graph of the number of UCB-MSCs migrated toward a lower compartment of a transwell chamber when PKH-labeled UCB-MSCs placed in an upper compartment of the transwell chamber and each of U-87 MG, LS174-T, NC-37, and NIH3T3 cells placed in the lower compartment of the transwell chamber are co-cultured, wherein: in (A), a left bar indicates a case in which the cell number of cell lines in the lower compartment in the transwell chamber is 1.times.10.sup.5 cells and a right bar indicates a case in which the cell number of cell lines in the lower compartment in the transwell chamber is 5.times.10.sup.5 cells, and in both cases, the number of UCB-MSCs is 1.times.10.sup.5 cells and in (B), a left fluorescent microscopic image shows PKH26-labeled UCB-MSCs migrated toward the lower compartment of the transwell chamber when a human cell line-free medium only is used (control), and a right fluorescent microscopic image shows PKH26-labeled UCB-MSCs migrated toward the lower compartment of the transwell chamber when-UCB-MSCs are co-cultured with U-87 MG cells;

[0253] FIG. 4 is a graph of the number of UCB-MSCs migrated toward the lower compartment of the transwell chamber when PKH-labeled UCB-MSCs placed in the upper compartment of the transwell chamber and each of U-87 MG, KATO III, A549, PLC/PRF5, LN18, U138, and U251 cells placed in the lower compartment of the transwell chamber are co-cultured (A and C), wherein (B) is an fluorescent microscopic image of PKH26-labeled UCB-MSCs migrated toward the lower compartment, and (D) is a graph of the number of UCB-MSCs migrated when UCB-MSCs are co-cultured with U-87 MG cells, or with U87 MG cells-free cultured-conditioned media which is prepared by culturing U87 MG cells in media and then removing U87 MG cells from the media;

[0254] FIG. 5 is a graph for comparing tropisms of BM-MSCs and UCB-MSCs for U-87 MG cells, wherein each of PKH-labeled UCB-MSCs and PKH-labeled BM-MSCs placed in the upper compartment in the transwell chamber and U-87 MG cells placed in the lower compartment in the transwell chamber are co-cultured and the number of PKH-labeled UCB-MSCs migrated toward the lower compartment is compared with the number of PKH-labeled BM-MSCs, wherein a left bar indicates a case in which U-87 MG cells do not exist and a right bar indicates a case in which U-87 MG cells exist (the number of U-87 MG cells is 5.times.10.sup.5, and in both cases, the number of MSCs is 1.times.10.sup.5;

[0255] FIG. 6 is a graph of chemotactic indices of UCB-MSCs when UCB-MSCs are co-cultured with cancer cell lines (A549, HeLa, and U-87 MG cells);

[0256] FIG. 7 shows results obtained by analyzing cell lysates and cell culture supernatants through a cytokine array after each of NC37, LS174-T, and U-87 MG cells is co-cultured with UCB-MSCs;

[0257] FIG. 8 shows analysis results obtained by collecting conditioned media in which UCB-MSCs were cultured alone, U-87 MG cells were cultured alone, and both of UCB-MSCs to and U-87 MG cells were co-cultured, incubating the conditioned media on an array membrane, and then visualizing the incubated results with ECL reagents, wherein (A) shows cytokine antibody array analysis results from the conditioned media with UCB-MSCs and medium control, (B) shows analysis results when the conditioned media in which U-87 MG only is cultured is used and when the media in which a UCB-MSCs and U-87 MG are co-cultured is used, and (C) shows mRNA isolation results from UCB-MSCs (left) cultured with or without U-87 MG cells or UCB-MSCs, and from U-87 MG cells cultured with and without UCB-MSCs, wherein RP-PCT is performed with IL-8 specific primers and GAPDH is used as a control group;

[0258] FIG. 9 is a graph for identifying the effect of IL-8 and GRO-.alpha., among the cytokines analyzed with reference to FIG. 8, on MSC migration, wherein (A) is a graph of cell migration toward the lower compartment when MSCs are treated with a recombinant IL-8 protein for 0, 1, 10, and 100 ng for 24 hours, (B) is a graph of cell migration toward the lower compartment when UCB-MSCs are pre-treated with 0.02, 0.2, and 2 .mu.g of a CXC chemokine receptor 1 (CXCR1) antibody that is known as a receptor of IL-8 in cells and then treated with 50 ng of IL-8 to promote the MSC migration. (*, p=0.007; **, p<0.001), (C) is a graph of cell migration toward the lower compartment when UCB-MSCs are treated with GRO-.alpha. (*, p<0.005), and (D) is a graph of cell migration when MSCs are treated with Monocyte chemoattractant protein-1 (MCP-1);

[0259] FIG. 10 consists of (A), (B), (C), and (D), wherein (A) and (B) are graphs of the amount of IL-8 secreted in the cultured media with U-87 MG, KATO Ill, A549, PLC/PRF5, LN18, U138, and U251 cells, measured by ELISA, (C) is a graph of cell migration when IL-8 gene is introduced to A549 cell secreting a low level of IL-8 and overexpressed, and (D) is a graph of the amount of IL-8 secreted in the media in the condition of (C), measured by ELISA;

[0260] FIG. 11 are graphs for comparing tropisms of UCB-MSCs and BM-MSCs for U-87 MG cells, wherein (A) is a graph for comparing tropism of UCB-MSCs and BM-MSCs moved toward the lower compartment, with respect to U-87 MG cells, and (B) is a graph for comparing tropism of UCB-MSCs and BM-MSCs when UCB-MSCs and BM-MSCs are treated with IL-8 for 14 hours;

[0261] FIG. 12 show analysis results for comparing expression levels of CXC chemokine receptor 1 and CXC chemokine receptor 2 (CXCR1 and CXCR2), which are known as IL-8 receptors, in UCB-MSCs and BM-MSCs, by measuring mRNA and protein, wherein (A) shows analysis results when mRNA is separated from each of UCB-MSCs and BM-MSCs and RT-PCR was performed with CXCR1 and CXCR2 primers in UCB-MSCs and BM-MSCs, wherein the separated RNA was quantified with reference to GAPDH reacted with each sample, (B) is a graph of expression levels of CXCR1 and CXCR2 by measuring the band intensity of mRNA of each gel obtained from (A) with a densitometer (* and **, p<0.001; n=4), (C) shows analysis results of protein expression levels of CXCR1 and CXCR2 in UCB-MSCs and BM-MSCs by performing a immunostaining process and anti-CXCR1 and CXCR2 antibodies (.times.400), and (D) shows analysis results obtained by immunostaining UCB-MSCs and BM-MSCs with a secondary antibody only instead of anti-CXCR1 and CXCR2 antibodies to identify antigen specificity of the anti-CXCR1 and CXCR2 antibodies;

[0262] FIG. 13 is a fluorescent microscopic image of UCB-MSCs to which a gene coding green fluorescent protein (GFP) is introduced and overexpressed;

[0263] FIG. 14 shows results of an experiment in which each of the gene coding GFP and an empty gene is overexpressed in UCB-MSCs. Said UCB-MSCs are placed in a upper compartment in a transwell and U-87 MG cells are placed in a lower compartment in the transwell and cocultured for 24 hours, and then UCB-MSCs migrated toward the lower compartment are identified; and

[0264] FIG. 15 shows primer sequences used in Examples of the present invention.

Sequence CWU 1 SEQUENCE LISTING <160> NUMBER OF SEQ ID NOS: 110 <210> SEQ ID NO 1 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic construct <400> SEQUENCE: 1 accacagtcc atgccatcac 20 <210> SEQ ID NO 2 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic construct <400> SEQUENCE: 2 tccaccaccc tgttgctgta 20 <210> SEQ ID NO 3 <211> LENGTH: 22 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic construct <400> SEQUENCE: 3 tcctgatttc tgcagctctg tg 22 <210> SEQ ID NO 4 <211> LENGTH: 22 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic construct <400> SEQUENCE: 4 tgcttgaagt ttcactggca tc 22 <210> SEQ ID NO 5 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic construct <400> SEQUENCE: 5 gagccccgaa tctgacatta 20 <210> SEQ ID NO 6 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic construct <400> SEQUENCE: 6 gcagacactg caacacacct 20 <210> SEQ ID NO 7 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic construct <400> SEQUENCE: 7 attctgggca tccttcacag 20 <210> SEQ ID NO 8 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic construct <400> SEQUENCE: 8 tgcacttagg caggaggtct 20 <210> SEQ ID NO 9 <211> LENGTH: 403 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 9 Met Thr Ala Ile Ile Lys Glu Ile Val Ser Arg Asn Lys Arg Arg Tyr 1 5 10 15 Gln Glu Asp Gly Phe Asp Leu Asp Leu Thr Tyr Ile Tyr Pro Asn Ile 20 25 30 Ile Ala Met Gly Phe Pro Ala Glu Arg Leu Glu Gly Val Tyr Arg Asn 35 40 45 Asn Ile Asp Asp Val Val Arg Phe Leu Asp Ser Lys His Lys Asn His 50 55 60 Tyr Lys Ile Tyr Asn Leu Cys Ala Glu Arg His Tyr Asp Thr Ala Lys 65 70 75 80 Phe Asn Cys Arg Val Ala Gln Tyr Pro Phe Glu Asp His Asn Pro Pro 85 90 95 Gln Leu Glu Leu Ile Lys Pro Phe Cys Glu Asp Leu Asp Gln Trp Leu 100 105 110 Ser Glu Asp Asp Asn His Val Ala Ala Ile His Cys Lys Ala Gly Lys 115 120 125 Gly Arg Thr Gly Val Met Ile Cys Ala Tyr Leu Leu His Arg Gly Lys 130 135 140 Phe Leu Lys Ala Gln Glu Ala Leu Asp Phe Tyr Gly Glu Val Arg Thr 145 150 155 160 Arg Asp Lys Lys Gly Val Thr Ile Pro Ser Gln Arg Arg Tyr Val Tyr 165 170 175 Tyr Tyr Ser Tyr Leu Leu Lys Asn His Leu Asp Tyr Arg Pro Val Ala 180 185 190 Leu Leu Phe His Lys Met Met Phe Glu Thr Ile Pro Met Phe Ser Gly 195 200 205 Gly Thr Cys Asn Pro Gln Phe Val Val Cys Gln Leu Lys Val Lys Ile 210 215 220 Tyr Ser Ser Asn Ser Gly Pro Thr Arg Arg Glu Asp Lys Phe Met Tyr 225 230 235 240 Phe Glu Phe Pro Gln Pro Leu Pro Val Cys Gly Asp Ile Lys Val Glu 245 250 255 Phe Phe His Lys Gln Asn Lys Met Leu Lys Lys Asp Lys Met Phe His 260 265 270 Phe Trp Val Asn Thr Phe Phe Ile Pro Gly Pro Glu Glu Thr Ser Glu 275 280 285 Lys Val Glu Asn Gly Ser Leu Cys Asp Gln Glu Ile Asp Ser Ile Cys 290 295 300 Ser Ile Glu Arg Ala Asp Asn Asp Lys Glu Tyr Leu Val Leu Thr Leu 305 310 315 320 Thr Lys Asn Asp Leu Asp Lys Ala Asn Lys Asp Lys Ala Asn Arg Tyr 325 330 335 Phe Ser Pro Asn Phe Lys Val Lys Leu Tyr Phe Thr Lys Thr Val Glu 340 345 350 Glu Pro Ser Asn Pro Glu Ala Ser Ser Ser Thr Ser Val Thr Pro Asp 355 360 365 Val Ser Asp Asn Glu Pro Asp His Tyr Arg Tyr Ser Asp Thr Thr Asp 370 375 380 Ser Asp Pro Glu Asn Glu Pro Phe Asp Glu Asp Gln His Thr Gln Ile 385 390 395 400 Thr Lys Val <210> SEQ ID NO 10 <211> LENGTH: 375 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 10 Met Asp Ala Leu Gln Leu Ala Asn Ser Ala Phe Ala Val Asp Leu Phe 1 5 10 15 Lys Gln Leu Cys Glu Lys Glu Pro Leu Gly Asn Val Leu Phe Ser Pro 20 25 30 Ile Cys Leu Ser Thr Ser Leu Ser Leu Ala Gln Val Gly Ala Lys Gly 35 40 45 Asp Thr Ala Asn Glu Ile Gly Gln Val Leu His Phe Glu Asn Val Lys 50 55 60 Asp Val Pro Phe Gly Phe Gln Thr Val Thr Ser Asp Val Asn Lys Leu 65 70 75 80 Ser Ser Phe Tyr Ser Leu Lys Leu Ile Lys Arg Leu Tyr Val Asp Lys 85 90 95 Ser Leu Asn Leu Ser Thr Glu Phe Ile Ser Ser Thr Lys Arg Pro Tyr 100 105 110 Ala Lys Glu Leu Glu Thr Val Asp Phe Lys Asp Lys Leu Glu Glu Thr 115 120 125 Lys Gly Gln Ile Asn Asn Ser Ile Lys Asp Leu Thr Asp Gly His Phe 130 135 140 Glu Asn Ile Leu Ala Asp Asn Ser Val Asn Asp Gln Thr Lys Ile Leu 145 150 155 160 Val Val Asn Ala Ala Tyr Phe Val Gly Lys Trp Met Lys Lys Phe Ser 165 170 175 Glu Ser Glu Thr Lys Glu Cys Pro Phe Arg Val Asn Lys Thr Asp Thr 180 185 190 Lys Pro Val Gln Met Met Asn Met Glu Ala Thr Phe Cys Met Gly Asn 195 200 205 Ile Asp Ser Ile Asn Cys Lys Ile Ile Glu Leu Pro Phe Gln Asn Lys 210 215 220 His Leu Ser Met Phe Ile Leu Leu Pro Lys Asp Val Glu Asp Glu Ser 225 230 235 240 Thr Gly Leu Glu Lys Ile Glu Lys Gln Leu Asn Ser Glu Ser Leu Ser 245 250 255 Gln Trp Thr Asn Pro Ser Thr Met Ala Asn Ala Lys Val Lys Leu Ser 260 265 270 Ile Pro Lys Phe Lys Val Glu Lys Met Ile Asp Pro Lys Ala Cys Leu 275 280 285 Glu Asn Leu Gly Leu Lys His Ile Phe Ser Glu Asp Thr Ser Asp Phe 290 295 300 Ser Gly Met Ser Glu Thr Lys Gly Val Ala Leu Ser Asn Val Ile His 305 310 315 320 Lys Val Cys Leu Glu Ile Thr Glu Asp Gly Gly Asp Ser Ile Glu Val 325 330 335 Pro Gly Ala Arg Ile Leu Gln His Lys Asp Glu Leu Asn Ala Asp His 340 345 350 Pro Phe Ile Tyr Ile Ile Arg His Asn Lys Thr Arg Asn Ile Ile Phe 355 360 365 Phe Gly Lys Phe Cys Ser Pro 370 375 <210> SEQ ID NO 11 <211> LENGTH: 429 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 11 Met Ala Ser Asn Ser Ile Phe Asp Ser Phe Pro Thr Tyr Ser Pro Thr 1 5 10 15 Phe Ile Arg Asp Pro Ser Thr Ser Arg Arg Phe Thr Pro Pro Ser Pro 20 25 30 Ala Phe Pro Cys Gly Gly Gly Gly Gly Lys Met Gly Glu Asn Ser Gly 35 40 45 Ala Leu Ser Ala Gln Ala Ala Val Gly Pro Gly Gly Arg Ala Arg Pro 50 55 60 Glu Val Arg Ser Met Val Asp Val Leu Ala Asp His Ala Gly Glu Leu 65 70 75 80 Val Arg Thr Asp Ser Pro Asn Phe Leu Cys Ser Val Leu Pro Ser His 85 90 95 Trp Arg Cys Asn Lys Thr Leu Pro Val Ala Phe Lys Val Val Ala Leu 100 105 110 Gly Asp Val Pro Asp Gly Thr Val Val Thr Val Met Ala Gly Asn Asp 115 120 125 Glu Asn Tyr Ser Ala Glu Leu Arg Asn Ala Ser Ala Val Met Lys Asn 130 135 140 Gln Val Ala Arg Phe Asn Asp Leu Arg Phe Val Gly Arg Ser Gly Arg 145 150 155 160 Gly Lys Ser Phe Thr Leu Thr Ile Thr Val Phe Thr Asn Pro Thr Gln 165 170 175 Val Ala Thr Tyr His Arg Ala Ile Lys Val Thr Val Asp Gly Pro Arg 180 185 190 Glu Pro Arg Arg His Arg Gln Lys Leu Glu Asp Gln Thr Lys Pro Phe 195 200 205 Pro Asp Arg Phe Gly Asp Leu Glu Arg Leu Arg Met Arg Val Thr Pro 210 215 220 Ser Thr Pro Ser Pro Arg Gly Ser Leu Ser Thr Thr Ser His Phe Ser 225 230 235 240 Ser Gln Pro Gln Thr Pro Ile Gln Gly Thr Ser Glu Leu Asn Pro Phe 245 250 255 Ser Asp Pro Arg Gln Phe Asp Arg Ser Phe Pro Thr Leu Pro Thr Leu 260 265 270 Thr Glu Ser Arg Phe Pro Asp Pro Arg Met His Tyr Pro Gly Ala Met 275 280 285 Ser Ala Ala Phe Pro Tyr Ser Ala Thr Pro Ser Gly Thr Ser Ile Ser 290 295 300 Ser Leu Ser Val Ala Gly Met Pro Ala Thr Ser Arg Phe His His Thr 305 310 315 320 Tyr Leu Pro Pro Pro Tyr Pro Gly Ala Pro Gln Asn Gln Ser Gly Pro 325 330 335 Phe Gln Ala Asn Pro Ser Pro Tyr His Leu Tyr Tyr Gly Thr Ser Ser 340 345 350 Gly Ser Tyr Gln Phe Ser Met Val Ala Gly Ser Ser Ser Gly Gly Asp 355 360 365 Arg Ser Pro Thr Arg Met Leu Ala Ser Cys Thr Ser Ser Ala Ala Ser 370 375 380 Val Ala Ala Gly Asn Leu Met Asn Pro Ser Leu Gly Gly Gln Ser Asp 385 390 395 400 Gly Val Glu Ala Asp Gly Ser His Ser Asn Ser Pro Thr Ala Leu Ser 405 410 415 Thr Pro Gly Arg Met Asp Glu Ala Val Trp Arg Pro Tyr 420 425 <210> SEQ ID NO 12 <211> LENGTH: 415 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 12 Met Arg Ile Pro Val Asp Pro Ser Thr Ser Arg Arg Phe Thr Pro Pro 1 5 10 15 Ser Pro Ala Phe Pro Cys Gly Gly Gly Gly Gly Lys Met Gly Glu Asn 20 25 30 Ser Gly Ala Leu Ser Ala Gln Ala Ala Val Gly Pro Gly Gly Arg Ala 35 40 45 Arg Pro Glu Val Arg Ser Met Val Asp Val Leu Ala Asp His Ala Gly 50 55 60 Glu Leu Val Arg Thr Asp Ser Pro Asn Phe Leu Cys Ser Val Leu Pro 65 70 75 80 Ser His Trp Arg Cys Asn Lys Thr Leu Pro Val Ala Phe Lys Val Val 85 90 95 Ala Leu Gly Asp Val Pro Asp Gly Thr Val Val Thr Val Met Ala Gly 100 105 110 Asn Asp Glu Asn Tyr Ser Ala Glu Leu Arg Asn Ala Ser Ala Val Met 115 120 125 Lys Asn Gln Val Ala Arg Phe Asn Asp Leu Arg Phe Val Gly Arg Ser 130 135 140 Gly Arg Gly Lys Ser Phe Thr Leu Thr Ile Thr Val Phe Thr Asn Pro 145 150 155 160 Thr Gln Val Ala Thr Tyr His Arg Ala Ile Lys Val Thr Val Asp Gly 165 170 175 Pro Arg Glu Pro Arg Arg His Arg Gln Lys Leu Glu Asp Gln Thr Lys 180 185 190 Pro Phe Pro Asp Arg Phe Gly Asp Leu Glu Arg Leu Arg Met Arg Val 195 200 205 Thr Pro Ser Thr Pro Ser Pro Arg Gly Ser Leu Ser Thr Thr Ser His 210 215 220 Phe Ser Ser Gln Pro Gln Thr Pro Ile Gln Gly Thr Ser Glu Leu Asn 225 230 235 240 Pro Phe Ser Asp Pro Arg Gln Phe Asp Arg Ser Phe Pro Thr Leu Pro 245 250 255 Thr Leu Thr Glu Ser Arg Phe Pro Asp Pro Arg Met His Tyr Pro Gly 260 265 270 Ala Met Ser Ala Ala Phe Pro Tyr Ser Ala Thr Pro Ser Gly Thr Ser 275 280 285 Ile Ser Ser Leu Ser Val Ala Gly Met Pro Ala Thr Ser Arg Phe His 290 295 300 His Thr Tyr Leu Pro Pro Pro Tyr Pro Gly Ala Pro Gln Asn Gln Ser 305 310 315 320 Gly Pro Phe Gln Ala Asn Pro Ser Pro Tyr His Leu Tyr Tyr Gly Thr 325 330 335 Ser Ser Gly Ser Tyr Gln Phe Ser Met Val Ala Gly Ser Ser Ser Gly 340 345 350 Gly Asp Arg Ser Pro Thr Arg Met Leu Ala Ser Cys Thr Ser Ser Ala 355 360 365 Ala Ser Val Ala Ala Gly Asn Leu Met Asn Pro Ser Leu Gly Gly Gln 370 375 380 Ser Asp Gly Val Glu Ala Asp Gly Ser His Ser Asn Ser Pro Thr Ala 385 390 395 400 Leu Ser Thr Pro Gly Arg Met Asp Glu Ala Val Trp Arg Pro Tyr 405 410 415 <210> SEQ ID NO 13 <211> LENGTH: 178 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 13 Met Ser Gly Gly Lys Tyr Val Asp Ser Glu Gly His Leu Tyr Thr Val 1 5 10 15 Pro Ile Arg Glu Gln Gly Asn Ile Tyr Lys Pro Asn Asn Lys Ala Met 20 25 30 Ala Asp Glu Leu Ser Glu Lys Gln Val Tyr Asp Ala His Thr Lys Glu 35 40 45 Ile Asp Leu Val Asn Arg Asp Pro Lys His Leu Asn Asp Asp Val Val 50 55 60 Lys Ile Asp Phe Glu Asp Val Ile Ala Glu Pro Glu Gly Thr His Ser 65 70 75 80 Phe Asp Gly Ile Trp Lys Ala Ser Phe Thr Thr Phe Thr Val Thr Lys 85 90 95 Tyr Trp Phe Tyr Arg Leu Leu Ser Ala Leu Phe Gly Ile Pro Met Ala 100 105 110 Leu Ile Trp Gly Ile Tyr Phe Ala Ile Leu Ser Phe Leu His Ile Trp 115 120 125 Ala Val Val Pro Cys Ile Lys Ser Phe Leu Ile Glu Ile Gln Cys Ile 130 135 140 Ser Arg Val Tyr Ser Ile Tyr Val His Thr Val Cys Asp Pro Leu Phe 145 150 155 160 Glu Ala Val Gly Lys Ile Phe Ser Asn Val Arg Ile Asn Leu Gln Lys 165 170 175 Glu Ile <210> SEQ ID NO 14 <211> LENGTH: 177 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 14 Met Val Leu Leu Ser Thr Leu Gly Ile Val Phe Gln Gly Glu Gly Pro 1 5 10 15 Pro Ile Ser Ser Cys Asp Thr Gly Thr Met Ala Asn Cys Glu Arg Thr 20 25 30 Phe Ile Ala Ile Lys Pro Asp Gly Val Gln Arg Gly Leu Val Gly Glu 35 40 45 Ile Ile Lys Arg Phe Glu Gln Lys Gly Phe Arg Leu Val Gly Leu Lys 50 55 60 Phe Met Gln Ala Ser Glu Asp Leu Leu Lys Glu His Tyr Val Asp Leu 65 70 75 80 Lys Asp Arg Pro Phe Phe Ala Gly Leu Val Lys Tyr Met His Ser Gly 85 90 95 Pro Val Val Ala Met Val Trp Glu Gly Leu Asn Val Val Lys Thr Gly 100 105 110 Arg Val Met Leu Gly Glu Thr Asn Pro Ala Asp Ser Lys Pro Gly Thr 115 120 125 Ile Arg Gly Asp Phe Cys Ile Gln Val Gly Arg Asn Ile Ile His Gly 130 135 140 Ser Asp Ser Val Glu Ser Ala Glu Lys Glu Ile Gly Leu Trp Phe His 145 150 155 160 Pro Glu Glu Leu Val Asp Tyr Thr Ser Cys Ala Gln Asn Trp Ile Tyr 165 170 175 Glu <210> SEQ ID NO 15 <211> LENGTH: 152 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 15 Met Ala Asn Cys Glu Arg Thr Phe Ile Ala Ile Lys Pro Asp Gly Val 1 5 10 15 Gln Arg Gly Leu Val Gly Glu Ile Ile Lys Arg Phe Glu Gln Lys Gly 20 25 30 Phe Arg Leu Val Gly Leu Lys Phe Met Gln Ala Ser Glu Asp Leu Leu 35 40 45 Lys Glu His Tyr Val Asp Leu Lys Asp Arg Pro Phe Phe Ala Gly Leu 50 55 60 Val Lys Tyr Met His Ser Gly Pro Val Val Ala Met Val Trp Glu Gly 65 70 75 80 Leu Asn Val Val Lys Thr Gly Arg Val Met Leu Gly Glu Thr Asn Pro 85 90 95 Ala Asp Ser Lys Pro Gly Thr Ile Arg Gly Asp Phe Cys Ile Gln Val 100 105 110 Gly Arg Asn Ile Ile His Gly Ser Asp Ser Val Glu Ser Ala Glu Lys 115 120 125 Glu Ile Gly Leu Trp Phe His Pro Glu Glu Leu Val Asp Tyr Thr Ser 130 135 140 Cys Ala Gln Asn Trp Ile Tyr Glu 145 150 <210> SEQ ID NO 16 <211> LENGTH: 928 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 16 Met Pro Pro Lys Thr Pro Arg Lys Thr Ala Ala Thr Ala Ala Ala Ala 1 5 10 15 Ala Ala Glu Pro Pro Ala Pro Pro Pro Pro Pro Pro Pro Glu Glu Asp 20 25 30 Pro Glu Gln Asp Ser Gly Pro Glu Asp Leu Pro Leu Val Arg Leu Glu 35 40 45 Phe Glu Glu Thr Glu Glu Pro Asp Phe Thr Ala Leu Cys Gln Lys Leu 50 55 60 Lys Ile Pro Asp His Val Arg Glu Arg Ala Trp Leu Thr Trp Glu Lys 65 70 75 80 Val Ser Ser Val Asp Gly Val Leu Gly Gly Tyr Ile Gln Lys Lys Lys 85 90 95 Glu Leu Trp Gly Ile Cys Ile Phe Ile Ala Ala Val Asp Leu Asp Glu 100 105 110 Met Ser Phe Thr Phe Thr Glu Leu Gln Lys Asn Ile Glu Ile Ser Val 115 120 125 His Lys Phe Phe Asn Leu Leu Lys Glu Ile Asp Thr Ser Thr Lys Val 130 135 140 Asp Asn Ala Met Ser Arg Leu Leu Lys Lys Tyr Asp Val Leu Phe Ala 145 150 155 160 Leu Phe Ser Lys Leu Glu Arg Thr Cys Glu Leu Ile Tyr Leu Thr Gln 165 170 175 Pro Ser Ser Ser Ile Ser Thr Glu Ile Asn Ser Ala Leu Val Leu Lys 180 185 190 Val Ser Trp Ile Thr Phe Leu Leu Ala Lys Gly Glu Val Leu Gln Met 195 200 205 Glu Asp Asp Leu Val Ile Ser Phe Gln Leu Met Leu Cys Val Leu Asp 210 215 220 Tyr Phe Ile Lys Leu Ser Pro Pro Met Leu Leu Lys Glu Pro Tyr Lys 225 230 235 240 Thr Ala Val Ile Pro Ile Asn Gly Ser Pro Arg Thr Pro Arg Arg Gly 245 250 255 Gln Asn Arg Ser Ala Arg Ile Ala Lys Gln Leu Glu Asn Asp Thr Arg 260 265 270 Ile Ile Glu Val Leu Cys Lys Glu His Glu Cys Asn Ile Asp Glu Val 275 280 285 Lys Asn Val Tyr Phe Lys Asn Phe Ile Pro Phe Met Asn Ser Leu Gly 290 295 300 Leu Val Thr Ser Asn Gly Leu Pro Glu Val Glu Asn Leu Ser Lys Arg 305 310 315 320 Tyr Glu Glu Ile Tyr Leu Lys Asn Lys Asp Leu Asp Ala Arg Leu Phe 325 330 335 Leu Asp His Asp Lys Thr Leu Gln Thr Asp Ser Ile Asp Ser Phe Glu 340 345 350 Thr Gln Arg Thr Pro Arg Lys Ser Asn Leu Asp Glu Glu Val Asn Val 355 360 365 Ile Pro Pro His Thr Pro Val Arg Thr Val Met Asn Thr Ile Gln Gln 370 375 380 Leu Met Met Ile Leu Asn Ser Ala Ser Asp Gln Pro Ser Glu Asn Leu 385 390 395 400 Ile Ser Tyr Phe Asn Asn Cys Thr Val Asn Pro Lys Glu Ser Ile Leu 405 410 415 Lys Arg Val Lys Asp Ile Gly Tyr Ile Phe Lys Glu Lys Phe Ala Lys 420 425 430 Ala Val Gly Gln Gly Cys Val Glu Ile Gly Ser Gln Arg Tyr Lys Leu 435 440 445 Gly Val Arg Leu Tyr Tyr Arg Val Met Glu Ser Met Leu Lys Ser Glu 450 455 460 Glu Glu Arg Leu Ser Ile Gln Asn Phe Ser Lys Leu Leu Asn Asp Asn 465 470 475 480 Ile Phe His Met Ser Leu Leu Ala Cys Ala Leu Glu Val Val Met Ala 485 490 495 Thr Tyr Ser Arg Ser Thr Ser Gln Asn Leu Asp Ser Gly Thr Asp Leu 500 505 510 Ser Phe Pro Trp Ile Leu Asn Val Leu Asn Leu Lys Ala Phe Asp Phe 515 520 525 Tyr Lys Val Ile Glu Ser Phe Ile Lys Ala Glu Gly Asn Leu Thr Arg 530 535 540 Glu Met Ile Lys His Leu Glu Arg Cys Glu His Arg Ile Met Glu Ser 545 550 555 560 Leu Ala Trp Leu Ser Asp Ser Pro Leu Phe Asp Leu Ile Lys Gln Ser 565 570 575 Lys Asp Arg Glu Gly Pro Thr Asp His Leu Glu Ser Ala Cys Pro Leu 580 585 590 Asn Leu Pro Leu Gln Asn Asn His Thr Ala Ala Asp Met Tyr Leu Ser 595 600 605 Pro Val Arg Ser Pro Lys Lys Lys Gly Ser Thr Thr Arg Val Asn Ser 610 615 620 Thr Ala Asn Ala Glu Thr Gln Ala Thr Ser Ala Phe Gln Thr Gln Lys 625 630 635 640 Pro Leu Lys Ser Thr Ser Leu Ser Leu Phe Tyr Lys Lys Val Tyr Arg 645 650 655 Leu Ala Tyr Leu Arg Leu Asn Thr Leu Cys Glu Arg Leu Leu Ser Glu 660 665 670 His Pro Glu Leu Glu His Ile Ile Trp Thr Leu Phe Gln His Thr Leu 675 680 685 Gln Asn Glu Tyr Glu Leu Met Arg Asp Arg His Leu Asp Gln Ile Met 690 695 700 Met Cys Ser Met Tyr Gly Ile Cys Lys Val Lys Asn Ile Asp Leu Lys 705 710 715 720 Phe Lys Ile Ile Val Thr Ala Tyr Lys Asp Leu Pro His Ala Val Gln 725 730 735 Glu Thr Phe Lys Arg Val Leu Ile Lys Glu Glu Glu Tyr Asp Ser Ile 740 745 750 Ile Val Phe Tyr Asn Ser Val Phe Met Gln Arg Leu Lys Thr Asn Ile 755 760 765 Leu Gln Tyr Ala Ser Thr Arg Pro Pro Thr Leu Ser Pro Ile Pro His 770 775 780 Ile Pro Arg Ser Pro Tyr Lys Phe Pro Ser Ser Pro Leu Arg Ile Pro 785 790 795 800 Gly Gly Asn Ile Tyr Ile Ser Pro Leu Lys Ser Pro Tyr Lys Ile Ser 805 810 815 Glu Gly Leu Pro Thr Pro Thr Lys Met Thr Pro Arg Ser Arg Ile Leu 820 825 830 Val Ser Ile Gly Glu Ser Phe Gly Thr Ser Glu Lys Phe Gln Lys Ile 835 840 845 Asn Gln Met Val Cys Asn Ser Asp Arg Val Leu Lys Arg Ser Ala Glu 850 855 860 Gly Ser Asn Pro Pro Lys Pro Leu Lys Lys Leu Arg Phe Asp Ile Glu 865 870 875 880 Gly Ser Asp Glu Ala Asp Gly Ser Lys His Leu Pro Gly Glu Ser Lys 885 890 895 Phe Gln Gln Lys Leu Ala Glu Met Thr Ser Thr Arg Thr Arg Met Gln 900 905 910 Lys Gln Lys Met Asn Asp Ser Met Asp Thr Ser Asn Lys Glu Glu Lys 915 920 925 <210> SEQ ID NO 17 <211> LENGTH: 1043 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 17 Met Pro Leu Leu Glu Gly Ser Val Gly Val Glu Asp Leu Val Leu Leu 1 5 10 15 Glu Pro Leu Val Glu Glu Ser Leu Leu Lys Asn Leu Gln Leu Arg Tyr 20 25 30 Glu Asn Lys Glu Ile Tyr Thr Tyr Ile Gly Asn Val Val Ile Ser Val 35 40 45 Asn Pro Tyr Gln Gln Leu Pro Ile Tyr Gly Pro Glu Phe Ile Ala Lys 50 55 60 Tyr Gln Asp Tyr Thr Phe Tyr Glu Leu Lys Pro His Ile Tyr Ala Leu 65 70 75 80 Ala Asn Val Ala Tyr Gln Ser Leu Arg Asp Arg Asp Arg Asp Gln Cys 85 90 95 Ile Leu Ile Thr Gly Glu Ser Gly Ser Gly Lys Thr Glu Ala Ser Lys 100 105 110 Leu Val Met Ser Tyr Val Ala Ala Val Cys Gly Lys Gly Glu Gln Val 115 120 125 Asn Ser Val Lys Glu Gln Leu Leu Gln Ser Asn Pro Val Leu Glu Ala 130 135 140 Phe Gly Asn Ala Lys Thr Ile Arg Asn Asn Asn Ser Ser Arg Phe Gly 145 150 155 160 Lys Tyr Met Asp Ile Glu Phe Asp Phe Lys Gly Ser Pro Leu Gly Gly 165 170 175 Val Ile Thr Asn Tyr Leu Leu Glu Lys Ser Arg Leu Val Lys Gln Leu 180 185 190 Lys Gly Glu Arg Asn Phe His Ile Phe Tyr Gln Leu Leu Ala Gly Ala 195 200 205 Asp Glu Gln Leu Leu Lys Ala Leu Lys Leu Glu Arg Asp Thr Thr Gly 210 215 220 Tyr Ala Tyr Leu Asn His Glu Val Ser Arg Val Asp Gly Met Asp Asp 225 230 235 240 Ala Ser Ser Phe Arg Ala Val Gln Ser Ala Met Ala Val Ile Gly Phe 245 250 255 Ser Glu Glu Glu Ile Arg Gln Val Leu Glu Val Thr Ser Met Val Leu 260 265 270 Lys Leu Gly Asn Val Leu Val Ala Asp Glu Phe Gln Ala Ser Gly Ile 275 280 285 Pro Ala Ser Gly Ile Arg Asp Gly Arg Gly Val Arg Glu Ile Gly Glu 290 295 300 Met Val Gly Leu Asn Ser Glu Glu Val Glu Arg Ala Leu Cys Ser Arg 305 310 315 320 Thr Met Glu Thr Ala Lys Glu Lys Val Val Thr Ala Leu Asn Val Met 325 330 335 Gln Ala Gln Tyr Ala Arg Asp Ala Leu Ala Lys Asn Ile Tyr Ser Arg 340 345 350 Leu Phe Asp Trp Ile Val Asn Arg Ile Asn Glu Ser Ile Lys Val Gly 355 360 365 Ile Gly Glu Lys Lys Lys Val Met Gly Val Leu Asp Ile Tyr Gly Phe 370 375 380 Glu Ile Leu Glu Asp Asn Ser Phe Glu Gln Phe Val Ile Asn Tyr Cys 385 390 395 400 Asn Glu Lys Leu Gln Gln Val Phe Ile Glu Met Thr Leu Lys Glu Glu 405 410 415 Gln Glu Glu Tyr Lys Arg Glu Gly Ile Pro Trp Thr Lys Val Asp Tyr 420 425 430 Phe Asp Asn Gly Ile Ile Cys Lys Leu Ile Glu His Asn Gln Arg Gly 435 440 445 Ile Leu Ala Met Leu Asp Glu Glu Cys Leu Arg Pro Gly Val Val Ser 450 455 460 Asp Ser Thr Phe Leu Ala Lys Leu Asn Gln Leu Phe Ser Lys His Gly 465 470 475 480 His Tyr Glu Ser Lys Val Thr Gln Asn Ala Gln Arg Gln Tyr Asp His 485 490 495 Thr Met Gly Leu Ser Cys Phe Arg Ile Cys His Tyr Ala Gly Lys Val 500 505 510 Thr Tyr Asn Val Thr Ser Phe Ile Asp Lys Asn Asn Asp Leu Leu Phe 515 520 525 Arg Asp Leu Leu Gln Ala Met Trp Lys Ala Gln His Pro Leu Leu Arg 530 535 540 Ser Leu Phe Pro Glu Gly Asn Pro Lys Gln Ala Ser Leu Lys Arg Pro 545 550 555 560 Pro Thr Ala Gly Ala Gln Phe Lys Ser Ser Val Ala Ile Leu Met Lys 565 570 575 Asn Leu Tyr Ser Lys Ser Pro Asn Tyr Ile Arg Cys Ile Lys Pro Asn 580 585 590 Glu His Gln Gln Arg Gly Gln Phe Ser Ser Asp Leu Val Ala Thr Gln 595 600 605 Ala Arg Tyr Leu Gly Leu Leu Glu Asn Val Arg Val Arg Arg Ala Gly 610 615 620 Tyr Ala His Arg Gln Gly Tyr Gly Pro Phe Leu Glu Arg Tyr Arg Leu 625 630 635 640 Leu Ser Arg Ser Thr Trp Pro His Trp Asn Gly Gly Asp Arg Glu Gly 645 650 655 Val Glu Lys Val Leu Gly Glu Leu Ser Met Ser Ser Gly Glu Leu Ala 660 665 670 Phe Gly Lys Thr Lys Ile Phe Ile Arg Ser Pro Lys Thr Leu Phe Tyr 675 680 685 Leu Glu Glu Gln Arg Arg Leu Arg Leu Gln Gln Leu Ala Thr Leu Ile 690 695 700 Gln Lys Ile Tyr Arg Gly Trp Arg Cys Arg Thr His Tyr Gln Leu Met 705 710 715 720 Arg Lys Ser Gln Ile Leu Ile Ser Ser Trp Phe Arg Gly Asn Met Gln 725 730 735 Lys Lys Cys Tyr Gly Lys Ile Lys Ala Ser Val Leu Leu Ile Gln Ala 740 745 750 Phe Val Arg Gly Trp Lys Ala Arg Lys Asn Tyr Arg Lys Tyr Phe Arg 755 760 765 Ser Glu Ala Ala Leu Thr Leu Ala Asp Phe Ile Tyr Lys Ser Met Val 770 775 780 Gln Lys Phe Leu Leu Gly Leu Lys Asn Asn Leu Pro Ser Thr Asn Val 785 790 795 800 Leu Asp Lys Thr Trp Pro Ala Ala Pro Tyr Lys Cys Leu Ser Thr Ala 805 810 815 Asn Gln Glu Leu Gln Gln Leu Phe Tyr Gln Trp Lys Cys Lys Arg Phe 820 825 830 Arg Asp Gln Leu Ser Pro Lys Gln Val Glu Ile Leu Arg Glu Lys Leu 835 840 845 Cys Ala Ser Glu Leu Phe Lys Gly Lys Lys Ala Ser Tyr Pro Gln Ser 850 855 860 Val Pro Ile Pro Phe Cys Gly Asp Tyr Ile Gly Leu Gln Gly Asn Pro 865 870 875 880 Lys Leu Gln Lys Leu Lys Gly Gly Glu Glu Gly Pro Val Leu Met Ala 885 890 895 Glu Ala Val Lys Lys Val Asn Arg Gly Asn Gly Lys Thr Ser Ser Arg 900 905 910 Ile Leu Leu Leu Thr Lys Gly His Val Ile Leu Thr Asp Thr Lys Lys 915 920 925 Ser Gln Ala Lys Ile Val Ile Gly Leu Asp Asn Val Ala Gly Val Ser 930 935 940 Val Thr Ser Leu Lys Asp Gly Leu Phe Ser Leu His Leu Ser Glu Met 945 950 955 960 Ser Ser Val Gly Ser Lys Gly Asp Phe Leu Leu Val Ser Glu His Val 965 970 975 Ile Glu Leu Leu Thr Lys Met Tyr Arg Ala Val Leu Asp Ala Thr Gln 980 985 990 Arg Gln Leu Thr Val Thr Val Thr Glu Lys Phe Ser Val Arg Phe Lys 995 1000 1005 Glu Asn Ser Val Ala Val Lys Val Val Gln Gly Pro Ala Gly Gly Asp 1010 1015 1020 Asn Ser Lys Leu Arg Tyr Lys Lys Lys Gly Ser His Cys Leu Glu Val 1025 1030 1035 1040 Thr Val Gln <210> SEQ ID NO 18 <211> LENGTH: 248 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 18 Met Ala Ala Gly Met Tyr Leu Glu His Tyr Leu Asp Ser Ile Glu Asn 1 5 10 15 Leu Pro Phe Glu Leu Gln Arg Asn Phe Gln Leu Met Arg Asp Leu Asp 20 25 30 Gln Arg Thr Glu Asp Leu Lys Ala Glu Ile Asp Lys Leu Ala Thr Glu 35 40 45 Tyr Met Ser Ser Ala Arg Ser Leu Ser Ser Glu Glu Lys Leu Ala Leu 50 55 60 Leu Lys Gln Ile Gln Glu Ala Tyr Gly Lys Cys Lys Glu Phe Gly Asp 65 70 75 80 Asp Lys Val Gln Leu Ala Met Gln Thr Tyr Glu Met Val Asp Lys His 85 90 95 Ile Arg Arg Leu Asp Thr Asp Leu Ala Arg Phe Glu Ala Asp Leu Lys 100 105 110 Glu Lys Gln Ile Glu Ser Ser Asp Tyr Asp Ser Ser Ser Ser Lys Gly 115 120 125 Lys Lys Ser Arg Thr Gln Lys Glu Lys Lys Ala Ala Arg Ala Arg Ser 130 135 140 Lys Gly Lys Asn Ser Asp Glu Glu Ala Pro Lys Thr Ala Gln Lys Lys 145 150 155 160 Leu Lys Leu Val Arg Thr Ser Pro Glu Tyr Gly Met Pro Ser Val Thr 165 170 175 Phe Gly Ser Val His Pro Ser Asp Val Leu Asp Met Pro Val Asp Pro 180 185 190 Asn Glu Pro Thr Tyr Cys Leu Cys His Gln Val Ser Tyr Gly Glu Met 195 200 205 Ile Gly Cys Asp Asn Pro Asp Cys Ser Ile Glu Trp Phe His Phe Ala 210 215 220 Cys Val Gly Leu Thr Thr Lys Pro Arg Gly Lys Trp Phe Cys Pro Arg 225 230 235 240 Cys Ser Gln Glu Arg Lys Lys Lys 245 <210> SEQ ID NO 19 <211> LENGTH: 246 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 19 Met Ala Ala Gly Met Tyr Leu Glu His Tyr Leu Asp Ser Ile Glu Asn 1 5 10 15 Leu Pro Phe Glu Leu Gln Arg Asn Phe Gln Leu Met Arg Asp Leu Asp 20 25 30 Gln Arg Thr Glu Asp Leu Lys Ala Glu Ile Asp Lys Leu Ala Thr Glu 35 40 45 Tyr Met Ser Ser Ala Arg Ser Leu Ser Ser Glu Glu Lys Leu Ala Leu 50 55 60 Leu Lys Gln Ile Gln Glu Ala Tyr Gly Lys Cys Lys Glu Phe Gly Asp 65 70 75 80 Asp Lys Val Gln Leu Ala Met Gln Thr Tyr Glu Met Val Asp Lys His 85 90 95 Ile Arg Arg Leu Asp Thr Asp Leu Ala Arg Phe Glu Ala Asp Leu Lys 100 105 110 Glu Lys Gln Ile Glu Ser Ser Asp Tyr Asp Ser Ser Ser Ser Lys Glu 115 120 125 Gly Arg Thr Gln Lys Glu Lys Lys Ala Ala Arg Ala Arg Ser Lys Gly 130 135 140 Lys Asn Ser Asp Glu Glu Ala Pro Lys Thr Ala Gln Lys Lys Leu Lys 145 150 155 160 Leu Val Arg Thr Ser Pro Glu Tyr Gly Met Pro Ser Val Thr Phe Gly 165 170 175 Ser Val His Pro Ser Asp Val Leu Asp Met Pro Val Asp Pro Asn Glu 180 185 190 Pro Thr Tyr Cys Leu Cys His Gln Val Ser Tyr Gly Glu Met Ile Gly 195 200 205 Cys Asp Asn Pro Asp Cys Ser Ile Glu Trp Phe His Phe Ala Cys Val 210 215 220 Gly Leu Thr Thr Lys Pro Arg Gly Lys Trp Phe Cys Pro Arg Cys Ser 225 230 235 240 Gln Glu Arg Lys Lys Lys 245 <210> SEQ ID NO 20 <211> LENGTH: 245 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 20 Met Ala Ala Gly Met Tyr Leu Glu His Tyr Leu Asp Ser Ile Glu Asn 1 5 10 15 Leu Pro Phe Glu Leu Gln Arg Asn Phe Gln Leu Met Arg Asp Leu Asp 20 25 30 Gln Arg Thr Glu Asp Leu Lys Ala Glu Ile Asp Lys Leu Ala Thr Glu 35 40 45 Tyr Met Ser Ser Ala Arg Ser Leu Ser Ser Glu Glu Lys Leu Ala Leu 50 55 60 Leu Lys Gln Ile Gln Glu Ala Tyr Gly Lys Cys Lys Glu Phe Gly Asp 65 70 75 80 Asp Lys Val Gln Leu Ala Met Gln Thr Tyr Glu Met Val Asp Lys His 85 90 95 Ile Arg Arg Leu Asp Thr Asp Leu Ala Arg Phe Glu Ala Asp Leu Lys 100 105 110 Glu Lys Gln Ile Glu Ser Ser Asp Tyr Asp Ser Ser Ser Ser Lys Gly 115 120 125 Arg Thr Gln Lys Glu Lys Lys Ala Ala Arg Ala Arg Ser Lys Gly Lys 130 135 140 Asn Ser Asp Glu Glu Ala Pro Lys Thr Ala Gln Lys Lys Leu Lys Leu 145 150 155 160 Val Arg Thr Ser Pro Glu Tyr Gly Met Pro Ser Val Thr Phe Gly Ser 165 170 175 Val His Pro Ser Asp Val Leu Asp Met Pro Val Asp Pro Asn Glu Pro 180 185 190 Thr Tyr Cys Leu Cys His Gln Val Ser Tyr Gly Glu Met Ile Gly Cys 195 200 205 Asp Asn Pro Asp Cys Ser Ile Glu Trp Phe His Phe Ala Cys Val Gly 210 215 220 Leu Thr Thr Lys Pro Arg Gly Lys Trp Phe Cys Pro Arg Cys Ser Gln 225 230 235 240 Glu Arg Lys Lys Lys 245 <210> SEQ ID NO 21 <211> LENGTH: 225 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 21 Met Ala Ala Gly Met Tyr Leu Glu His Tyr Leu Asp Asn Leu Lys Ala 1 5 10 15 Glu Ile Asp Lys Leu Ala Thr Glu Tyr Met Ser Ser Ala Arg Ser Leu 20 25 30 Ser Ser Glu Glu Lys Leu Ala Leu Leu Lys Gln Ile Gln Glu Ala Tyr 35 40 45 Gly Lys Cys Lys Glu Phe Gly Asp Asp Lys Val Gln Leu Ala Met Gln 50 55 60 Thr Tyr Glu Met Val Asp Lys His Ile Arg Arg Leu Asp Thr Asp Leu 65 70 75 80 Ala Arg Phe Glu Ala Asp Leu Lys Glu Lys Gln Ile Glu Ser Ser Asp 85 90 95 Tyr Asp Ser Ser Ser Ser Lys Gly Lys Lys Lys Gly Arg Thr Gln Lys 100 105 110 Glu Lys Lys Ala Ala Arg Ala Arg Ser Lys Gly Lys Asn Ser Asp Glu 115 120 125 Glu Ala Pro Lys Thr Ala Gln Lys Lys Leu Lys Leu Val Arg Thr Ser 130 135 140 Pro Glu Tyr Gly Met Pro Ser Val Thr Phe Gly Ser Val His Pro Ser 145 150 155 160 Asp Val Leu Asp Met Pro Val Asp Pro Asn Glu Pro Thr Tyr Cys Leu 165 170 175 Cys His Gln Val Ser Tyr Gly Glu Met Ile Gly Cys Asp Asn Pro Asp 180 185 190 Cys Ser Ile Glu Trp Phe His Phe Ala Cys Val Gly Leu Thr Thr Lys 195 200 205 Pro Arg Gly Lys Trp Phe Cys Pro Arg Cys Ser Gln Glu Arg Lys Lys 210 215 220 Lys 225 <210> SEQ ID NO 22 <211> LENGTH: 179 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 22 Met Ala Ala Gly Met Tyr Leu Glu His Tyr Leu Asp Ser Ile Glu Asn 1 5 10 15 Leu Pro Phe Glu Leu Gln Arg Asn Phe Gln Leu Met Arg Asp Leu Asp 20 25 30 Gln Arg Thr Glu Asp Leu Lys Ala Glu Ile Asp Lys Leu Ala Thr Glu 35 40 45 Tyr Met Ser Ser Ala Arg Ser Leu Ser Ser Glu Glu Lys Leu Ala Leu 50 55 60 Leu Lys Gln Ile Gln Glu Ala Tyr Gly Lys Cys Lys Glu Phe Gly Asp 65 70 75 80 Asp Lys Val Gln Leu Ala Met Gln Thr Tyr Glu Met Val Asp Lys His 85 90 95 Ile Arg Arg Leu Asp Thr Asp Leu Ala Arg Phe Glu Ala Asp Leu Lys 100 105 110 Glu Lys Gln Ile Glu Ser Ser Asp Tyr Asp Ser Ser Ser Ser Lys Gly 115 120 125 Lys Lys Lys Gly Arg Thr Gln Lys Glu Lys Lys Ala Ala Arg Ala Arg 130 135 140 Ser Lys Gly Lys Asn Ser Asp Glu Glu Ala Pro Lys Thr Ala Gln Lys 145 150 155 160 Lys Leu Lys Leu Val Arg Thr Val Pro Leu Ser Gly Ser Ile Leu Pro 165 170 175 Val Trp Gly <210> SEQ ID NO 23 <211> LENGTH: 249 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 23 Met Ala Ala Gly Met Tyr Leu Glu His Tyr Leu Asp Ser Ile Glu Asn 1 5 10 15 Leu Pro Phe Glu Leu Gln Arg Asn Phe Gln Leu Met Arg Asp Leu Asp 20 25 30 Gln Arg Thr Glu Asp Leu Lys Ala Glu Ile Asp Lys Leu Ala Thr Glu 35 40 45 Tyr Met Ser Ser Ala Arg Ser Leu Ser Ser Glu Glu Lys Leu Ala Leu 50 55 60 Leu Lys Gln Ile Gln Glu Ala Tyr Gly Lys Cys Lys Glu Phe Gly Asp 65 70 75 80 Asp Lys Val Gln Leu Ala Met Gln Thr Tyr Glu Met Val Asp Lys His 85 90 95 Ile Arg Arg Leu Asp Thr Asp Leu Ala Arg Phe Glu Ala Asp Leu Lys 100 105 110 Glu Lys Gln Ile Glu Ser Ser Asp Tyr Asp Ser Ser Ser Ser Lys Gly 115 120 125 Lys Lys Lys Gly Arg Thr Gln Lys Glu Lys Lys Ala Ala Arg Ala Arg 130 135 140 Ser Lys Gly Lys Asn Ser Asp Glu Glu Ala Pro Lys Thr Ala Gln Lys 145 150 155 160 Lys Leu Lys Leu Val Arg Thr Ser Pro Glu Tyr Gly Met Pro Ser Val 165 170 175 Thr Phe Gly Ser Val His Pro Ser Asp Val Leu Asp Met Pro Val Asp 180 185 190 Pro Asn Glu Pro Thr Tyr Cys Leu Cys His Gln Val Ser Tyr Gly Glu 195 200 205 Met Ile Gly Cys Asp Asn Pro Asp Cys Ser Ile Glu Trp Phe His Phe 210 215 220 Ala Cys Val Gly Leu Thr Thr Lys Pro Arg Gly Lys Trp Phe Cys Pro 225 230 235 240 Arg Cys Ser Gln Glu Arg Lys Lys Lys 245 <210> SEQ ID NO 24 <211> LENGTH: 142 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 24 Met Gly Ala Pro Thr Leu Pro Pro Ala Trp Gln Pro Phe Leu Lys Asp 1 5 10 15 His Arg Ile Ser Thr Phe Lys Asn Trp Pro Phe Leu Glu Gly Cys Ala 20 25 30 Cys Thr Pro Glu Arg Met Ala Glu Ala Gly Phe Ile His Cys Pro Thr 35 40 45 Glu Asn Glu Pro Asp Leu Ala Gln Cys Phe Phe Cys Phe Lys Glu Leu 50 55 60 Glu Gly Trp Glu Pro Asp Asp Asp Pro Ile Glu Glu His Lys Lys His 65 70 75 80 Ser Ser Gly Cys Ala Phe Leu Ser Val Lys Lys Gln Phe Glu Glu Leu 85 90 95 Thr Leu Gly Glu Phe Leu Lys Leu Asp Arg Glu Arg Ala Lys Asn Lys 100 105 110 Ile Ala Lys Glu Thr Asn Asn Lys Lys Lys Glu Phe Glu Glu Thr Ala 115 120 125 Glu Lys Val Arg Arg Ala Ile Glu Gln Leu Ala Ala Met Asp 130 135 140 <210> SEQ ID NO 25 <211> LENGTH: 137 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 25 Met Gly Ala Pro Thr Leu Pro Pro Ala Trp Gln Pro Phe Leu Lys Asp 1 5 10 15 His Arg Ile Ser Thr Phe Lys Asn Trp Pro Phe Leu Glu Gly Cys Ala 20 25 30 Cys Thr Pro Glu Arg Met Ala Glu Ala Gly Phe Ile His Cys Pro Thr 35 40 45 Glu Asn Glu Pro Asp Leu Ala Gln Cys Phe Phe Cys Phe Lys Glu Leu 50 55 60 Glu Gly Trp Glu Pro Asp Asp Asp Pro Met Gln Arg Lys Pro Thr Ile 65 70 75 80 Arg Arg Lys Asn Leu Arg Lys Leu Arg Arg Lys Cys Ala Val Pro Ser 85 90 95 Ser Ser Trp Leu Pro Trp Ile Glu Ala Ser Gly Arg Ser Cys Leu Val 100 105 110 Pro Glu Trp Leu His His Phe Gln Gly Leu Phe Pro Gly Ala Thr Ser 115 120 125 Leu Pro Val Gly Pro Leu Ala Met Ser 130 135 <210> SEQ ID NO 26 <211> LENGTH: 165 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 26 Met Gly Ala Pro Thr Leu Pro Pro Ala Trp Gln Pro Phe Leu Lys Asp 1 5 10 15 His Arg Ile Ser Thr Phe Lys Asn Trp Pro Phe Leu Glu Gly Cys Ala 20 25 30 Cys Thr Pro Glu Arg Met Ala Glu Ala Gly Phe Ile His Cys Pro Thr 35 40 45 Glu Asn Glu Pro Asp Leu Ala Gln Cys Phe Phe Cys Phe Lys Glu Leu 50 55 60 Glu Gly Trp Glu Pro Asp Asp Asp Pro Ile Gly Pro Gly Thr Val Ala 65 70 75 80 Tyr Ala Cys Asn Thr Ser Thr Leu Gly Gly Arg Gly Gly Arg Ile Thr 85 90 95 Arg Glu Glu His Lys Lys His Ser Ser Gly Cys Ala Phe Leu Ser Val 100 105 110 Lys Lys Gln Phe Glu Glu Leu Thr Leu Gly Glu Phe Leu Lys Leu Asp 115 120 125 Arg Glu Arg Ala Lys Asn Lys Ile Ala Lys Glu Thr Asn Asn Lys Lys 130 135 140 Lys Glu Phe Glu Glu Thr Ala Glu Lys Val Arg Arg Ala Ile Glu Gln 145 150 155 160 Leu Ala Ala Met Asp 165 <210> SEQ ID NO 27 <211> LENGTH: 497 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 27 Met Thr Phe Asn Ser Phe Glu Gly Ser Lys Thr Cys Val Pro Ala Asp 1 5 10 15 Ile Asn Lys Glu Glu Glu Phe Val Glu Glu Phe Asn Arg Leu Lys Thr 20 25 30 Phe Ala Asn Phe Pro Ser Gly Ser Pro Val Ser Ala Ser Thr Leu Ala 35 40 45 Arg Ala Gly Phe Leu Tyr Thr Gly Glu Gly Asp Thr Val Arg Cys Phe 50 55 60 Ser Cys His Ala Ala Val Asp Arg Trp Gln Tyr Gly Asp Ser Ala Val 65 70 75 80 Gly Arg His Arg Lys Val Ser Pro Asn Cys Arg Phe Ile Asn Gly Phe 85 90 95 Tyr Leu Glu Asn Ser Ala Thr Gln Ser Thr Asn Ser Gly Ile Gln Asn 100 105 110 Gly Gln Tyr Lys Val Glu Asn Tyr Leu Gly Ser Arg Asp His Phe Ala 115 120 125 Leu Asp Arg Pro Ser Glu Thr His Ala Asp Tyr Leu Leu Arg Thr Gly 130 135 140 Gln Val Val Asp Ile Ser Asp Thr Ile Tyr Pro Arg Asn Pro Ala Met 145 150 155 160 Tyr Ser Glu Glu Ala Arg Leu Lys Ser Phe Gln Asn Trp Pro Asp Tyr 165 170 175 Ala His Leu Thr Pro Arg Glu Leu Ala Ser Ala Gly Leu Tyr Tyr Thr 180 185 190 Gly Ile Gly Asp Gln Val Gln Cys Phe Cys Cys Gly Gly Lys Leu Lys 195 200 205 Asn Trp Glu Pro Cys Asp Arg Ala Trp Ser Glu His Arg Arg His Phe 210 215 220 Pro Asn Cys Phe Phe Val Leu Gly Arg Asn Leu Asn Ile Arg Ser Glu 225 230 235 240 Ser Asp Ala Val Ser Ser Asp Arg Asn Phe Pro Asn Ser Thr Asn Leu 245 250 255 Pro Arg Asn Pro Ser Met Ala Asp Tyr Glu Ala Arg Ile Phe Thr Phe 260 265 270 Gly Thr Trp Ile Tyr Ser Val Asn Lys Glu Gln Leu Ala Arg Ala Gly 275 280 285 Phe Tyr Ala Leu Gly Glu Gly Asp Lys Val Lys Cys Phe His Cys Gly 290 295 300 Gly Gly Leu Thr Asp Trp Lys Pro Ser Glu Asp Pro Trp Glu Gln His 305 310 315 320 Ala Lys Trp Tyr Pro Gly Cys Lys Tyr Leu Leu Glu Gln Lys Gly Gln 325 330 335 Glu Tyr Ile Asn Asn Ile His Leu Thr His Ser Leu Glu Glu Cys Leu 340 345 350 Val Arg Thr Thr Glu Lys Thr Pro Ser Leu Thr Arg Arg Ile Asp Asp 355 360 365 Thr Ile Phe Gln Asn Pro Met Val Gln Glu Ala Ile Arg Met Gly Phe 370 375 380 Ser Phe Lys Asp Ile Lys Lys Ile Met Glu Glu Lys Ile Gln Ile Ser 385 390 395 400 Gly Ser Asn Tyr Lys Ser Leu Glu Val Leu Val Ala Asp Leu Val Asn 405 410 415 Ala Gln Lys Asp Ser Met Gln Asp Glu Ser Ser Gln Thr Ser Leu Gln 420 425 430 Lys Glu Ile Ser Thr Glu Glu Gln Leu Arg Arg Leu Gln Glu Glu Lys 435 440 445 Leu Cys Lys Ile Cys Met Asp Arg Asn Ile Ala Ile Val Phe Val Pro 450 455 460 Cys Gly His Leu Val Thr Cys Lys Gln Cys Ala Glu Ala Val Asp Lys 465 470 475 480 Cys Pro Met Cys Tyr Thr Val Ile Thr Phe Lys Gln Lys Ile Phe Met 485 490 495 Ser <210> SEQ ID NO 28 <211> LENGTH: 1403 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 28 Met Ala Thr Gln Gln Lys Ala Ser Asp Glu Arg Ile Ser Gln Phe Asp 1 5 10 15 His Asn Leu Leu Pro Glu Leu Ser Ala Leu Leu Gly Leu Asp Ala Val 20 25 30 Gln Leu Ala Lys Glu Leu Glu Glu Glu Glu Gln Lys Glu Arg Ala Lys 35 40 45 Met Gln Lys Gly Tyr Asn Ser Gln Met Arg Ser Glu Ala Lys Arg Leu 50 55 60 Lys Thr Phe Val Thr Tyr Glu Pro Tyr Ser Ser Trp Ile Pro Gln Glu 65 70 75 80 Met Ala Ala Ala Gly Phe Tyr Phe Thr Gly Val Lys Ser Gly Ile Gln 85 90 95 Cys Phe Cys Cys Ser Leu Ile Leu Phe Gly Ala Gly Leu Thr Arg Leu 100 105 110 Pro Ile Glu Asp His Lys Arg Phe His Pro Asp Cys Gly Phe Leu Leu 115 120 125 Asn Lys Asp Val Gly Asn Ile Ala Lys Tyr Asp Ile Arg Val Lys Asn 130 135 140 Leu Lys Ser Arg Leu Arg Gly Gly Lys Met Arg Tyr Gln Glu Glu Glu 145 150 155 160 Ala Arg Leu Ala Ser Phe Arg Asn Trp Pro Phe Tyr Val Gln Gly Ile 165 170 175 Ser Pro Cys Val Leu Ser Glu Ala Gly Phe Val Phe Thr Gly Lys Gln 180 185 190 Asp Thr Val Gln Cys Phe Ser Cys Gly Gly Cys Leu Gly Asn Trp Glu 195 200 205 Glu Gly Asp Asp Pro Trp Lys Glu His Ala Lys Trp Phe Pro Lys Cys 210 215 220 Glu Phe Leu Arg Ser Lys Lys Ser Ser Glu Glu Ile Thr Gln Tyr Ile 225 230 235 240 Gln Ser Tyr Lys Gly Phe Val Asp Ile Thr Gly Glu His Phe Val Asn 245 250 255 Ser Trp Val Gln Arg Glu Leu Pro Met Ala Ser Ala Tyr Cys Asn Asp 260 265 270 Ser Ile Phe Ala Tyr Glu Glu Leu Arg Leu Asp Ser Phe Lys Asp Trp 275 280 285 Pro Arg Glu Ser Ala Val Gly Val Ala Ala Leu Ala Lys Ala Gly Leu 290 295 300 Phe Tyr Thr Gly Ile Lys Asp Ile Val Gln Cys Phe Ser Cys Gly Gly 305 310 315 320 Cys Leu Glu Lys Trp Gln Glu Gly Asp Asp Pro Leu Asp Asp His Thr 325 330 335 Arg Cys Phe Pro Asn Cys Pro Phe Leu Gln Asn Met Lys Ser Ser Ala 340 345 350 Glu Val Thr Pro Asp Leu Gln Ser Arg Gly Glu Leu Cys Glu Leu Leu 355 360 365 Glu Thr Thr Ser Glu Ser Asn Leu Glu Asp Ser Ile Ala Val Gly Pro 370 375 380 Ile Val Pro Glu Met Ala Gln Gly Glu Ala Gln Trp Phe Gln Glu Ala 385 390 395 400 Lys Asn Leu Asn Glu Gln Leu Arg Ala Ala Tyr Thr Ser Ala Ser Phe 405 410 415 Arg His Met Ser Leu Leu Asp Ile Ser Ser Asp Leu Ala Thr Asp His 420 425 430 Leu Leu Gly Cys Asp Leu Ser Ile Ala Ser Lys His Ile Ser Lys Pro 435 440 445 Val Gln Glu Pro Leu Val Leu Pro Glu Val Phe Gly Asn Leu Asn Ser 450 455 460 Val Met Cys Val Glu Gly Glu Ala Gly Ser Gly Lys Thr Val Leu Leu 465 470 475 480 Lys Lys Ile Ala Phe Leu Trp Ala Ser Gly Cys Cys Pro Leu Leu Asn 485 490 495 Arg Phe Gln Leu Val Phe Tyr Leu Ser Leu Ser Ser Thr Arg Pro Asp 500 505 510 Glu Gly Leu Ala Ser Ile Ile Cys Asp Gln Leu Leu Glu Lys Glu Gly 515 520 525 Ser Val Thr Glu Met Cys Val Arg Asn Ile Ile Gln Gln Leu Lys Asn 530 535 540 Gln Val Leu Phe Leu Leu Asp Asp Tyr Lys Glu Ile Cys Ser Ile Pro 545 550 555 560 Gln Val Ile Gly Lys Leu Ile Gln Lys Asn His Leu Ser Arg Thr Cys 565 570 575 Leu Leu Ile Ala Val Arg Thr Asn Arg Ala Arg Asp Ile Arg Arg Tyr 580 585 590 Leu Glu Thr Ile Leu Glu Ile Lys Ala Phe Pro Phe Tyr Asn Thr Val 595 600 605 Cys Ile Leu Arg Lys Leu Phe Ser His Asn Met Thr Arg Leu Arg Lys 610 615 620 Phe Met Val Tyr Phe Gly Lys Asn Gln Ser Leu Gln Lys Ile Gln Lys 625 630 635 640 Thr Pro Leu Phe Val Ala Ala Ile Cys Ala His Trp Phe Gln Tyr Pro 645 650 655 Phe Asp Pro Ser Phe Asp Asp Val Ala Val Phe Lys Ser Tyr Met Glu 660 665 670 Arg Leu Ser Leu Arg Asn Lys Ala Thr Ala Glu Ile Leu Lys Ala Thr 675 680 685 Val Ser Ser Cys Gly Glu Leu Ala Leu Lys Gly Phe Phe Ser Cys Cys 690 695 700 Phe Glu Phe Asn Asp Asp Asp Leu Ala Glu Ala Gly Val Asp Glu Asp 705 710 715 720 Glu Asp Leu Thr Met Cys Leu Met Ser Lys Phe Thr Ala Gln Arg Leu 725 730 735 Arg Pro Phe Tyr Arg Phe Leu Ser Pro Ala Phe Gln Glu Phe Leu Ala 740 745 750 Gly Met Arg Leu Ile Glu Leu Leu Asp Ser Asp Arg Gln Glu His Gln 755 760 765 Asp Leu Gly Leu Tyr His Leu Lys Gln Ile Asn Ser Pro Met Met Thr 770 775 780 Val Ser Ala Tyr Asn Asn Phe Leu Asn Tyr Val Ser Ser Leu Pro Ser 785 790 795 800 Thr Lys Ala Gly Pro Lys Ile Val Ser His Leu Leu His Leu Val Asp 805 810 815 Asn Lys Glu Ser Leu Glu Asn Ile Ser Glu Asn Asp Asp Tyr Leu Lys 820 825 830 His Gln Pro Glu Ile Ser Leu Gln Met Gln Leu Leu Arg Gly Leu Trp 835 840 845 Gln Ile Cys Pro Gln Ala Tyr Phe Ser Met Val Ser Glu His Leu Leu 850 855 860 Val Leu Ala Leu Lys Thr Ala Tyr Gln Ser Asn Thr Val Ala Ala Cys 865 870 875 880 Ser Pro Phe Val Leu Gln Phe Leu Gln Gly Arg Thr Leu Thr Leu Gly 885 890 895 Ala Leu Asn Leu Gln Tyr Phe Phe Asp His Pro Glu Ser Leu Ser Leu 900 905 910 Leu Arg Ser Ile His Phe Pro Ile Arg Gly Asn Lys Thr Ser Pro Arg 915 920 925 Ala His Phe Ser Val Leu Glu Thr Cys Phe Asp Lys Ser Gln Val Pro 930 935 940 Thr Ile Asp Gln Asp Tyr Ala Ser Ala Phe Glu Pro Met Asn Glu Trp 945 950 955 960 Glu Arg Asn Leu Ala Glu Lys Glu Asp Asn Val Lys Ser Tyr Met Asp 965 970 975 Met Gln Arg Arg Ala Ser Pro Asp Leu Ser Thr Gly Tyr Trp Lys Leu 980 985 990 Ser Pro Lys Gln Tyr Lys Ile Pro Cys Leu Glu Val Asp Val Asn Asp 995 1000 1005 Ile Asp Val Val Gly Gln Asp Met Leu Glu Ile Leu Met Thr Val Phe 1010 1015 1020 Ser Ala Ser Gln Arg Ile Glu Leu His Leu Asn His Ser Arg Gly Phe 1025 1030 1035 1040 Ile Glu Ser Ile Arg Pro Ala Leu Glu Leu Ser Lys Ala Ser Val Thr 1045 1050 1055 Lys Cys Ser Ile Ser Lys Leu Glu Leu Ser Ala Ala Glu Gln Glu Leu 1060 1065 1070 Leu Leu Thr Leu Pro Ser Leu Glu Ser Leu Glu Val Ser Gly Thr Ile 1075 1080 1085 Gln Ser Gln Asp Gln Ile Phe Pro Asn Leu Asp Lys Phe Leu Cys Leu 1090 1095 1100 Lys Glu Leu Ser Val Asp Leu Glu Gly Asn Ile Asn Val Phe Ser Val 1105 1110 1115 1120 Ile Pro Glu Glu Phe Pro Asn Phe His His Met Glu Lys Leu Leu Ile 1125 1130 1135 Gln Ile Ser Ala Glu Tyr Asp Pro Ser Lys Leu Val Lys Leu Ile Gln 1140 1145 1150 Asn Ser Pro Asn Leu His Val Phe His Leu Lys Cys Asn Phe Phe Ser 1155 1160 1165 Asp Phe Gly Ser Leu Met Thr Met Leu Val Ser Cys Lys Lys Leu Thr 1170 1175 1180 Glu Ile Lys Phe Ser Asp Ser Phe Phe Gln Ala Val Pro Phe Val Ala 1185 1190 1195 1200 Ser Leu Pro Asn Phe Ile Ser Leu Lys Ile Leu Asn Leu Glu Gly Gln 1205 1210 1215 Gln Phe Pro Asp Glu Glu Thr Ser Glu Lys Phe Ala Tyr Ile Leu Gly 1220 1225 1230 Ser Leu Ser Asn Leu Glu Glu Leu Ile Leu Pro Thr Gly Asp Gly Ile 1235 1240 1245 Tyr Arg Val Ala Lys Leu Ile Ile Gln Gln Cys Gln Gln Leu His Cys 1250 1255 1260 Leu Arg Val Leu Ser Phe Phe Lys Thr Leu Asn Asp Asp Ser Val Val 1265 1270 1275 1280 Glu Ile Ala Lys Val Ala Ile Ser Gly Gly Phe Gln Lys Leu Glu Asn 1285 1290 1295 Leu Lys Leu Ser Ile Asn His Lys Ile Thr Glu Glu Gly Tyr Arg Asn 1300 1305 1310 Phe Phe Gln Ala Leu Asp Asn Met Pro Asn Leu Gln Glu Leu Asp Ile 1315 1320 1325 Ser Arg His Phe Thr Glu Cys Ile Lys Ala Gln Ala Thr Thr Val Lys 1330 1335 1340 Ser Leu Ser Gln Cys Val Leu Arg Leu Pro Arg Leu Ile Arg Leu Asn 1345 1350 1355 1360 Met Leu Ser Trp Leu Leu Asp Ala Asp Asp Ile Ala Leu Leu Asn Val 1365 1370 1375 Met Lys Glu Arg His Pro Gln Ser Lys Tyr Leu Thr Ile Leu Gln Lys 1380 1385 1390 Trp Ile Leu Pro Phe Ser Pro Ile Ile Gln Lys 1395 1400 <210> SEQ ID NO 29 <211> LENGTH: 1241 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 29 Met Pro Leu His Ile Gly Asp Phe Val Trp Asp Ser Lys Val His Ser 1 5 10 15 Leu Gln Ser Ser Leu Asn Ile Phe Ser Leu Leu Pro Thr Lys Gly Arg 20 25 30 Thr Glu His Leu Phe Phe Ser His Ile Leu Ser Phe His Trp Pro Ala 35 40 45 Phe Ser Ser Ile Arg Leu Glu Leu Trp Ile Asn Leu Arg Cys Glu Phe 50 55 60 Leu Arg Ser Lys Lys Ser Ser Glu Glu Ile Thr Gln Tyr Ile Gln Ser 65 70 75 80 Tyr Lys Gly Phe Val Asp Ile Thr Gly Glu His Phe Val Asn Ser Trp 85 90 95 Val Gln Arg Glu Leu Pro Met Ala Ser Ala Tyr Cys Asn Asp Ser Ile 100 105 110 Phe Ala Tyr Glu Glu Leu Arg Leu Asp Ser Phe Lys Asp Trp Pro Arg 115 120 125 Glu Ser Ala Val Gly Val Ala Ala Leu Ala Lys Ala Gly Leu Phe Tyr 130 135 140 Thr Gly Ile Lys Asp Ile Val Gln Cys Phe Ser Cys Gly Gly Cys Leu 145 150 155 160 Glu Lys Trp Gln Glu Gly Asp Asp Pro Leu Asp Asp His Thr Arg Cys 165 170 175 Phe Pro Asn Cys Pro Phe Leu Gln Asn Met Lys Ser Ser Ala Glu Val 180 185 190 Thr Pro Asp Leu Gln Ser Arg Gly Glu Leu Cys Glu Leu Leu Glu Thr 195 200 205 Thr Ser Glu Ser Asn Leu Glu Asp Ser Ile Ala Val Gly Pro Ile Val 210 215 220 Pro Glu Met Ala Gln Gly Glu Ala Gln Trp Phe Gln Glu Ala Lys Asn 225 230 235 240 Leu Asn Glu Gln Leu Arg Ala Ala Tyr Thr Ser Ala Ser Phe Arg His 245 250 255 Met Ser Leu Leu Asp Ile Ser Ser Asp Leu Ala Thr Asp His Leu Leu 260 265 270 Gly Cys Asp Leu Ser Ile Ala Ser Lys His Ile Ser Lys Pro Val Gln 275 280 285 Glu Pro Leu Val Leu Pro Glu Val Phe Gly Asn Leu Asn Ser Val Met 290 295 300 Cys Val Glu Gly Glu Ala Gly Ser Gly Lys Thr Val Leu Leu Lys Lys 305 310 315 320 Ile Ala Phe Leu Trp Ala Ser Gly Cys Cys Pro Leu Leu Asn Arg Phe 325 330 335 Gln Leu Val Phe Tyr Leu Ser Leu Ser Ser Thr Arg Pro Asp Glu Gly 340 345 350 Leu Ala Ser Ile Ile Cys Asp Gln Leu Leu Glu Lys Glu Gly Ser Val 355 360 365 Thr Glu Met Cys Val Arg Asn Ile Ile Gln Gln Leu Lys Asn Gln Val 370 375 380 Leu Phe Leu Leu Asp Asp Tyr Lys Glu Ile Cys Ser Ile Pro Gln Val 385 390 395 400 Ile Gly Lys Leu Ile Gln Lys Asn His Leu Ser Arg Thr Cys Leu Leu 405 410 415 Ile Ala Val Arg Thr Asn Arg Ala Arg Asp Ile Arg Arg Tyr Leu Glu 420 425 430 Thr Ile Leu Glu Ile Lys Ala Phe Pro Phe Tyr Asn Thr Val Cys Ile 435 440 445 Leu Arg Lys Leu Phe Ser His Asn Met Thr Arg Leu Arg Lys Phe Met 450 455 460 Val Tyr Phe Gly Lys Asn Gln Ser Leu Gln Lys Ile Gln Lys Thr Pro 465 470 475 480 Leu Phe Val Ala Ala Ile Cys Ala His Trp Phe Gln Tyr Pro Phe Asp 485 490 495 Pro Ser Phe Asp Asp Val Ala Val Phe Lys Ser Tyr Met Glu Arg Leu 500 505 510 Ser Leu Arg Asn Lys Ala Thr Ala Glu Ile Leu Lys Ala Thr Val Ser 515 520 525 Ser Cys Gly Glu Leu Ala Leu Lys Gly Phe Phe Ser Cys Cys Phe Glu 530 535 540 Phe Asn Asp Asp Asp Leu Ala Glu Ala Gly Val Asp Glu Asp Glu Asp 545 550 555 560 Leu Thr Met Cys Leu Met Ser Lys Phe Thr Ala Gln Arg Leu Arg Pro 565 570 575 Phe Tyr Arg Phe Leu Ser Pro Ala Phe Gln Glu Phe Leu Ala Gly Met 580 585 590 Arg Leu Ile Glu Leu Leu Asp Ser Asp Arg Gln Glu His Gln Asp Leu 595 600 605 Gly Leu Tyr His Leu Lys Gln Ile Asn Ser Pro Met Met Thr Val Ser 610 615 620 Ala Tyr Asn Asn Phe Leu Asn Tyr Val Ser Ser Leu Pro Ser Thr Lys 625 630 635 640 Ala Gly Pro Lys Ile Val Ser His Leu Leu His Leu Val Asp Asn Lys 645 650 655 Glu Ser Leu Glu Asn Ile Ser Glu Asn Asp Asp Tyr Leu Lys His Gln 660 665 670 Pro Glu Ile Ser Leu Gln Met Gln Leu Leu Arg Gly Leu Trp Gln Ile 675 680 685 Cys Pro Gln Ala Tyr Phe Ser Met Val Ser Glu His Leu Leu Val Leu 690 695 700 Ala Leu Lys Thr Ala Tyr Gln Ser Asn Thr Val Ala Ala Cys Ser Pro 705 710 715 720 Phe Val Leu Gln Phe Leu Gln Gly Arg Thr Leu Thr Leu Gly Ala Leu 725 730 735 Asn Leu Gln Tyr Phe Phe Asp His Pro Glu Ser Leu Ser Leu Leu Arg 740 745 750 Ser Ile His Phe Pro Ile Arg Gly Asn Lys Thr Ser Pro Arg Ala His 755 760 765 Phe Ser Val Leu Glu Thr Cys Phe Asp Lys Ser Gln Val Pro Thr Ile 770 775 780 Asp Gln Asp Tyr Ala Ser Ala Phe Glu Pro Met Asn Glu Trp Glu Arg 785 790 795 800 Asn Leu Ala Glu Lys Glu Asp Asn Val Lys Ser Tyr Met Asp Met Gln 805 810 815 Arg Arg Ala Ser Pro Asp Leu Ser Thr Gly Tyr Trp Lys Leu Ser Pro 820 825 830 Lys Gln Tyr Lys Ile Pro Cys Leu Glu Val Asp Val Asn Asp Ile Asp 835 840 845 Val Val Gly Gln Asp Met Leu Glu Ile Leu Met Thr Val Phe Ser Ala 850 855 860 Ser Gln Arg Ile Glu Leu His Leu Asn His Ser Arg Gly Phe Ile Glu 865 870 875 880 Ser Ile Arg Pro Ala Leu Glu Leu Ser Lys Ala Ser Val Thr Lys Cys 885 890 895 Ser Ile Ser Lys Leu Glu Leu Ser Ala Ala Glu Gln Glu Leu Leu Leu 900 905 910 Thr Leu Pro Ser Leu Glu Ser Leu Glu Val Ser Gly Thr Ile Gln Ser 915 920 925 Gln Asp Gln Ile Phe Pro Asn Leu Asp Lys Phe Leu Cys Leu Lys Glu 930 935 940 Leu Ser Val Asp Leu Glu Gly Asn Ile Asn Val Phe Ser Val Ile Pro 945 950 955 960 Glu Glu Phe Pro Asn Phe His His Met Glu Lys Leu Leu Ile Gln Ile 965 970 975 Ser Ala Glu Tyr Asp Pro Ser Lys Leu Val Lys Leu Ile Gln Asn Ser 980 985 990 Pro Asn Leu His Val Phe His Leu Lys Cys Asn Phe Phe Ser Asp Phe 995 1000 1005 Gly Ser Leu Met Thr Met Leu Val Ser Cys Lys Lys Leu Thr Glu Ile 1010 1015 1020 Lys Phe Ser Asp Ser Phe Phe Gln Ala Val Pro Phe Val Ala Ser Leu 1025 1030 1035 1040 Pro Asn Phe Ile Ser Leu Lys Ile Leu Asn Leu Glu Gly Gln Gln Phe 1045 1050 1055 Pro Asp Glu Glu Thr Ser Glu Lys Phe Ala Tyr Ile Leu Gly Ser Leu 1060 1065 1070 Ser Asn Leu Glu Glu Leu Ile Leu Pro Thr Gly Asp Gly Ile Tyr Arg 1075 1080 1085 Val Ala Lys Leu Ile Ile Gln Gln Cys Gln Gln Leu His Cys Leu Arg 1090 1095 1100 Val Leu Ser Phe Phe Lys Thr Leu Asn Asp Asp Ser Val Val Glu Ile 1105 1110 1115 1120 Ala Lys Val Ala Ile Ser Gly Gly Phe Gln Lys Leu Glu Asn Leu Lys 1125 1130 1135 Leu Ser Ile Asn His Lys Ile Thr Glu Glu Gly Tyr Arg Asn Phe Phe 1140 1145 1150 Gln Ala Leu Asp Asn Met Pro Asn Leu Gln Glu Leu Asp Ile Ser Arg 1155 1160 1165 His Phe Thr Glu Cys Ile Lys Ala Gln Ala Thr Thr Val Lys Ser Leu 1170 1175 1180 Ser Gln Cys Val Leu Arg Leu Pro Arg Leu Ile Arg Leu Asn Met Leu 1185 1190 1195 1200 Ser Trp Leu Leu Asp Ala Asp Asp Ile Ala Leu Leu Asn Val Met Lys 1205 1210 1215 Glu Arg His Pro Gln Ser Lys Tyr Leu Thr Ile Leu Gln Lys Trp Ile 1220 1225 1230 Leu Pro Phe Ser Pro Ile Ile Gln Lys 1235 1240 <210> SEQ ID NO 30 <211> LENGTH: 233 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 30 Met Ser Thr Glu Ser Met Ile Arg Asp Val Glu Leu Ala Glu Glu Ala 1 5 10 15 Leu Pro Lys Lys Thr Gly Gly Pro Gln Gly Ser Arg Arg Cys Leu Phe 20 25 30 Leu Ser Leu Phe Ser Phe Leu Ile Val Ala Gly Ala Thr Thr Leu Phe 35 40 45 Cys Leu Leu His Phe Gly Val Ile Gly Pro Gln Arg Glu Glu Phe Pro 50 55 60 Arg Asp Leu Ser Leu Ile Ser Pro Leu Ala Gln Ala Val Arg Ser Ser 65 70 75 80 Ser Arg Thr Pro Ser Asp Lys Pro Val Ala His Val Val Ala Asn Pro 85 90 95 Gln Ala Glu Gly Gln Leu Gln Trp Leu Asn Arg Arg Ala Asn Ala Leu 100 105 110 Leu Ala Asn Gly Val Glu Leu Arg Asp Asn Gln Leu Val Val Pro Ser 115 120 125 Glu Gly Leu Tyr Leu Ile Tyr Ser Gln Val Leu Phe Lys Gly Gln Gly 130 135 140 Cys Pro Ser Thr His Val Leu Leu Thr His Thr Ile Ser Arg Ile Ala 145 150 155 160 Val Ser Tyr Gln Thr Lys Val Asn Leu Leu Ser Ala Ile Lys Ser Pro 165 170 175 Cys Gln Arg Glu Thr Pro Glu Gly Ala Glu Ala Lys Pro Trp Tyr Glu 180 185 190 Pro Ile Tyr Leu Gly Gly Val Phe Gln Leu Glu Lys Gly Asp Arg Leu 195 200 205 Ser Ala Glu Ile Asn Arg Pro Asp Tyr Leu Asp Phe Ala Glu Ser Gly 210 215 220 Gln Val Tyr Phe Gly Ile Ile Ala Leu 225 230 <210> SEQ ID NO 31 <211> LENGTH: 189 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 31 Met Ala Ser Pro Phe Ala Leu Leu Met Val Leu Val Val Leu Ser Cys 1 5 10 15 Lys Ser Ser Cys Ser Leu Gly Cys Asp Leu Pro Glu Thr His Ser Leu 20 25 30 Asp Asn Arg Arg Thr Leu Met Leu Leu Ala Gln Met Ser Arg Ile Ser 35 40 45 Pro Ser Ser Cys Leu Met Asp Arg His Asp Phe Gly Phe Pro Gln Glu 50 55 60 Glu Phe Asp Gly Asn Gln Phe Gln Lys Ala Pro Ala Ile Ser Val Leu 65 70 75 80 His Glu Leu Ile Gln Gln Ile Phe Asn Leu Phe Thr Thr Lys Asp Ser 85 90 95 Ser Ala Ala Trp Asp Glu Asp Leu Leu Asp Lys Phe Cys Thr Glu Leu 100 105 110 Tyr Gln Gln Leu Asn Asp Leu Glu Ala Cys Val Met Gln Glu Glu Arg 115 120 125 Val Gly Glu Thr Pro Leu Met Asn Ala Asp Ser Ile Leu Ala Val Lys 130 135 140 Lys Tyr Phe Arg Arg Ile Thr Leu Tyr Leu Thr Glu Lys Lys Tyr Ser 145 150 155 160 Pro Cys Ala Trp Glu Val Val Arg Ala Glu Ile Met Arg Ser Leu Ser 165 170 175 Leu Ser Thr Asn Leu Gln Glu Arg Leu Arg Arg Lys Glu 180 185 <210> SEQ ID NO 32 <211> LENGTH: 187 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 32 Met Thr Asn Lys Cys Leu Leu Gln Ile Ala Leu Leu Leu Cys Phe Ser 1 5 10 15 Thr Thr Ala Leu Ser Met Ser Tyr Asn Leu Leu Gly Phe Leu Gln Arg 20 25 30 Ser Ser Asn Phe Gln Cys Gln Lys Leu Leu Trp Gln Leu Asn Gly Arg 35 40 45 Leu Glu Tyr Cys Leu Lys Asp Arg Met Asn Phe Asp Ile Pro Glu Glu 50 55 60 Ile Lys Gln Leu Gln Gln Phe Gln Lys Glu Asp Ala Ala Leu Thr Ile 65 70 75 80 Tyr Glu Met Leu Gln Asn Ile Phe Ala Ile Phe Arg Gln Asp Ser Ser 85 90 95 Ser Thr Gly Trp Asn Glu Thr Ile Val Glu Asn Leu Leu Ala Asn Val 100 105 110 Tyr His Gln Ile Asn His Leu Lys Thr Val Leu Glu Glu Lys Leu Glu 115 120 125 Lys Glu Asp Phe Thr Arg Gly Lys Leu Met Ser Ser Leu His Leu Lys 130 135 140 Arg Tyr Tyr Gly Arg Ile Leu His Tyr Leu Lys Ala Lys Glu Tyr Ser 145 150 155 160 His Cys Ala Trp Thr Ile Val Arg Val Glu Ile Leu Arg Asn Phe Tyr 165 170 175 Phe Ile Asn Arg Leu Thr Gly Tyr Leu Arg Asn 180 185 <210> SEQ ID NO 33 <211> LENGTH: 166 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 33 Met Lys Tyr Thr Ser Tyr Ile Leu Ala Phe Gln Leu Cys Ile Val Leu 1 5 10 15 Gly Ser Leu Gly Cys Tyr Cys Gln Asp Pro Tyr Val Lys Glu Ala Glu 20 25 30 Asn Leu Lys Lys Tyr Phe Asn Ala Gly His Ser Asp Val Ala Asp Asn 35 40 45 Gly Thr Leu Phe Leu Gly Ile Leu Lys Asn Trp Lys Glu Glu Ser Asp 50 55 60 Arg Lys Ile Met Gln Ser Gln Ile Val Ser Phe Tyr Phe Lys Leu Phe 65 70 75 80 Lys Asn Phe Lys Asp Asp Gln Ser Ile Gln Lys Ser Val Glu Thr Ile 85 90 95 Lys Glu Asp Met Asn Val Lys Phe Phe Asn Ser Asn Lys Lys Lys Arg 100 105 110 Asp Asp Phe Glu Lys Leu Thr Asn Tyr Ser Val Thr Asp Leu Asn Val 115 120 125 Gln Arg Lys Ala Ile His Glu Leu Ile Gln Val Met Ala Glu Leu Ser 130 135 140 Pro Ala Ala Lys Thr Gly Lys Arg Lys Arg Ser Gln Met Leu Phe Arg 145 150 155 160 Gly Arg Arg Ala Ser Gln 165 <210> SEQ ID NO 34 <211> LENGTH: 554 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 34 Met Thr Ala Pro Gly Ala Ala Gly Arg Cys Pro Pro Thr Thr Trp Leu 1 5 10 15 Gly Ser Leu Leu Leu Leu Val Cys Leu Leu Ala Ser Arg Ser Ile Thr 20 25 30 Glu Glu Val Ser Glu Tyr Cys Ser His Met Ile Gly Ser Gly His Leu 35 40 45 Gln Ser Leu Gln Arg Leu Ile Asp Ser Gln Met Glu Thr Ser Cys Gln 50 55 60 Ile Thr Phe Glu Phe Val Asp Gln Glu Gln Leu Lys Asp Pro Val Cys 65 70 75 80 Tyr Leu Lys Lys Ala Phe Leu Leu Val Gln Asp Ile Met Glu Asp Thr 85 90 95 Met Arg Phe Arg Asp Asn Thr Pro Asn Ala Ile Ala Ile Val Gln Leu 100 105 110 Gln Glu Leu Ser Leu Arg Leu Lys Ser Cys Phe Thr Lys Asp Tyr Glu 115 120 125 Glu His Asp Lys Ala Cys Val Arg Thr Phe Tyr Glu Thr Pro Leu Gln 130 135 140 Leu Leu Glu Lys Val Lys Asn Val Phe Asn Glu Thr Lys Asn Leu Leu 145 150 155 160 Asp Lys Asp Trp Asn Ile Phe Ser Lys Asn Cys Asn Asn Ser Phe Ala 165 170 175 Glu Cys Ser Ser Gln Asp Val Val Thr Lys Pro Asp Cys Asn Cys Leu 180 185 190 Tyr Pro Lys Ala Ile Pro Ser Ser Asp Pro Ala Ser Val Ser Pro His 195 200 205 Gln Pro Leu Ala Pro Ser Met Ala Pro Val Ala Gly Leu Thr Trp Glu 210 215 220 Asp Ser Glu Gly Thr Glu Gly Ser Ser Leu Leu Pro Gly Glu Gln Pro 225 230 235 240 Leu His Thr Val Asp Pro Gly Ser Ala Lys Gln Arg Pro Pro Arg Ser 245 250 255 Thr Cys Gln Ser Phe Glu Pro Pro Glu Thr Pro Val Val Lys Asp Ser 260 265 270 Thr Ile Gly Gly Ser Pro Gln Pro Arg Pro Ser Val Gly Ala Phe Asn 275 280 285 Pro Gly Met Glu Asp Ile Leu Asp Ser Ala Met Gly Thr Asn Trp Val 290 295 300 Pro Glu Glu Ala Ser Gly Glu Ala Ser Glu Ile Pro Val Pro Gln Gly 305 310 315 320 Thr Glu Leu Ser Pro Ser Arg Pro Gly Gly Gly Ser Met Gln Thr Glu 325 330 335 Pro Ala Arg Pro Ser Asn Phe Leu Ser Ala Ser Ser Pro Leu Pro Ala 340 345 350 Ser Ala Lys Gly Gln Gln Pro Ala Asp Val Thr Gly Thr Ala Leu Pro 355 360 365 Arg Val Gly Pro Val Arg Pro Thr Gly Gln Asp Trp Asn His Thr Pro 370 375 380 Gln Lys Thr Asp His Pro Ser Ala Leu Leu Arg Asp Pro Pro Glu Pro 385 390 395 400 Gly Ser Pro Arg Ile Ser Ser Leu Arg Pro Gln Gly Leu Ser Asn Pro 405 410 415 Ser Thr Leu Ser Ala Gln Pro Gln Leu Ser Arg Ser His Ser Ser Gly 420 425 430 Ser Val Leu Pro Leu Gly Glu Leu Glu Gly Arg Arg Ser Thr Arg Asp 435 440 445 Arg Arg Ser Pro Ala Glu Pro Glu Gly Gly Pro Ala Ser Glu Gly Ala 450 455 460 Ala Arg Pro Leu Pro Arg Phe Asn Ser Val Pro Leu Thr Asp Thr Gly 465 470 475 480 His Glu Arg Gln Ser Glu Gly Ser Ser Ser Pro Gln Leu Gln Glu Ser 485 490 495 Val Phe His Leu Leu Val Pro Ser Val Ile Leu Val Leu Leu Ala Val 500 505 510 Gly Gly Leu Leu Phe Tyr Arg Trp Arg Arg Arg Ser His Gln Glu Pro 515 520 525 Gln Arg Ala Asp Ser Pro Leu Glu Gln Pro Glu Gly Ser Pro Leu Thr 530 535 540 Gln Asp Asp Arg Gln Val Glu Leu Pro Val 545 550 <210> SEQ ID NO 35 <211> LENGTH: 554 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 35 Met Thr Ala Pro Gly Ala Ala Gly Arg Cys Pro Pro Thr Thr Trp Leu 1 5 10 15 Gly Ser Leu Leu Leu Leu Val Cys Leu Leu Ala Ser Arg Ser Ile Thr 20 25 30 Glu Glu Val Ser Glu Tyr Cys Ser His Met Ile Gly Ser Gly His Leu 35 40 45 Gln Ser Leu Gln Arg Leu Ile Asp Ser Gln Met Glu Thr Ser Cys Gln 50 55 60 Ile Thr Phe Glu Phe Val Asp Gln Glu Gln Leu Lys Asp Pro Val Cys 65 70 75 80 Tyr Leu Lys Lys Ala Phe Leu Leu Val Gln Asp Ile Met Glu Asp Thr 85 90 95 Met Arg Phe Arg Asp Asn Thr Pro Asn Ala Ile Ala Ile Val Gln Leu 100 105 110 Gln Glu Leu Ser Leu Arg Leu Lys Ser Cys Phe Thr Lys Asp Tyr Glu 115 120 125 Glu His Asp Lys Ala Cys Val Arg Thr Phe Tyr Glu Thr Pro Leu Gln 130 135 140 Leu Leu Glu Lys Val Lys Asn Val Phe Asn Glu Thr Lys Asn Leu Leu 145 150 155 160 Asp Lys Asp Trp Asn Ile Phe Ser Lys Asn Cys Asn Asn Ser Phe Ala 165 170 175 Glu Cys Ser Ser Gln Asp Val Val Thr Lys Pro Asp Cys Asn Cys Leu 180 185 190 Tyr Pro Lys Ala Ile Pro Ser Ser Asp Pro Ala Ser Val Ser Pro His 195 200 205 Gln Pro Leu Ala Pro Ser Met Ala Pro Val Ala Gly Leu Thr Trp Glu 210 215 220 Asp Ser Glu Gly Thr Glu Gly Ser Ser Leu Leu Pro Gly Glu Gln Pro 225 230 235 240 Leu His Thr Val Asp Pro Gly Ser Ala Lys Gln Arg Pro Pro Arg Ser 245 250 255 Thr Cys Gln Ser Phe Glu Pro Pro Glu Thr Pro Val Val Lys Asp Ser 260 265 270 Thr Ile Gly Gly Ser Pro Gln Pro Arg Pro Ser Val Gly Ala Phe Asn 275 280 285 Pro Gly Met Glu Asp Ile Leu Asp Ser Ala Met Gly Thr Asn Trp Val 290 295 300 Pro Glu Glu Ala Ser Gly Glu Ala Ser Glu Ile Pro Val Pro Gln Gly 305 310 315 320 Thr Glu Leu Ser Pro Ser Arg Pro Gly Gly Gly Ser Met Gln Thr Glu 325 330 335 Pro Ala Arg Pro Ser Asn Phe Leu Ser Ala Ser Ser Pro Leu Pro Ala 340 345 350 Ser Ala Lys Gly Gln Gln Pro Ala Asp Val Thr Gly Thr Ala Leu Pro 355 360 365 Arg Val Gly Pro Val Arg Pro Thr Gly Gln Asp Trp Asn His Thr Pro 370 375 380 Gln Lys Thr Asp His Pro Ser Ala Leu Leu Arg Asp Pro Pro Glu Pro 385 390 395 400 Gly Ser Pro Arg Ile Ser Ser Leu Arg Pro Gln Gly Leu Ser Asn Pro 405 410 415 Ser Thr Leu Ser Ala Gln Pro Gln Leu Ser Arg Ser His Ser Ser Gly 420 425 430 Ser Val Leu Pro Leu Gly Glu Leu Glu Gly Arg Arg Ser Thr Arg Asp 435 440 445 Arg Arg Ser Pro Ala Glu Pro Glu Gly Gly Pro Ala Ser Glu Gly Ala 450 455 460 Ala Arg Pro Leu Pro Arg Phe Asn Ser Val Pro Leu Thr Asp Thr Gly 465 470 475 480 His Glu Arg Gln Ser Glu Gly Ser Ser Ser Pro Gln Leu Gln Glu Ser 485 490 495 Val Phe His Leu Leu Val Pro Ser Val Ile Leu Val Leu Leu Ala Val 500 505 510 Gly Gly Leu Leu Phe Tyr Arg Trp Arg Arg Arg Ser His Gln Glu Pro 515 520 525 Gln Arg Ala Asp Ser Pro Leu Glu Gln Pro Glu Gly Ser Pro Leu Thr 530 535 540 Gln Asp Asp Arg Gln Val Glu Leu Pro Val 545 550 <210> SEQ ID NO 36 <211> LENGTH: 438 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 36 Met Thr Ala Pro Gly Ala Ala Gly Arg Cys Pro Pro Thr Thr Trp Leu 1 5 10 15 Gly Ser Leu Leu Leu Leu Val Cys Leu Leu Ala Ser Arg Ser Ile Thr 20 25 30 Glu Glu Val Ser Glu Tyr Cys Ser His Met Ile Gly Ser Gly His Leu 35 40 45 Gln Ser Leu Gln Arg Leu Ile Asp Ser Gln Met Glu Thr Ser Cys Gln 50 55 60 Ile Thr Phe Glu Phe Val Asp Gln Glu Gln Leu Lys Asp Pro Val Cys 65 70 75 80 Tyr Leu Lys Lys Ala Phe Leu Leu Val Gln Asp Ile Met Glu Asp Thr 85 90 95 Met Arg Phe Arg Asp Asn Thr Pro Asn Ala Ile Ala Ile Val Gln Leu 100 105 110 Gln Glu Leu Ser Leu Arg Leu Lys Ser Cys Phe Thr Lys Asp Tyr Glu 115 120 125 Glu His Asp Lys Ala Cys Val Arg Thr Phe Tyr Glu Thr Pro Leu Gln 130 135 140 Leu Leu Glu Lys Val Lys Asn Val Phe Asn Glu Thr Lys Asn Leu Leu 145 150 155 160 Asp Lys Asp Trp Asn Ile Phe Ser Lys Asn Cys Asn Asn Ser Phe Ala 165 170 175 Glu Cys Ser Ser Gln Asp Val Val Thr Lys Pro Asp Cys Asn Cys Leu 180 185 190 Tyr Pro Lys Ala Ile Pro Ser Ser Asp Pro Ala Ser Val Ser Pro His 195 200 205 Gln Pro Leu Ala Pro Ser Met Ala Pro Val Ala Gly Leu Thr Trp Glu 210 215 220 Asp Ser Glu Gly Thr Glu Gly Ser Ser Leu Leu Pro Gly Glu Gln Pro 225 230 235 240 Leu His Thr Val Asp Pro Gly Ser Ala Lys Gln Arg Pro Pro Arg Ser 245 250 255 Thr Cys Gln Ser Phe Glu Pro Pro Glu Thr Pro Val Val Lys Asp Ser 260 265 270 Thr Ile Gly Gly Ser Pro Gln Pro Arg Pro Ser Val Gly Ala Phe Asn 275 280 285 Pro Gly Met Glu Asp Ile Leu Asp Ser Ala Met Gly Thr Asn Trp Val 290 295 300 Pro Glu Glu Ala Ser Gly Glu Ala Ser Glu Ile Pro Val Pro Gln Gly 305 310 315 320 Thr Glu Leu Ser Pro Ser Arg Pro Gly Gly Gly Ser Met Gln Thr Glu 325 330 335 Pro Ala Arg Pro Ser Asn Phe Leu Ser Ala Ser Ser Pro Leu Pro Ala 340 345 350 Ser Ala Lys Gly Gln Gln Pro Ala Asp Val Thr Gly His Glu Arg Gln 355 360 365 Ser Glu Gly Ser Ser Ser Pro Gln Leu Gln Glu Ser Val Phe His Leu 370 375 380 Leu Val Pro Ser Val Ile Leu Val Leu Leu Ala Val Gly Gly Leu Leu 385 390 395 400 Phe Tyr Arg Trp Arg Arg Arg Ser His Gln Glu Pro Gln Arg Ala Asp 405 410 415 Ser Pro Leu Glu Gln Pro Glu Gly Ser Pro Leu Thr Gln Asp Asp Arg 420 425 430 Gln Val Glu Leu Pro Val 435 <210> SEQ ID NO 37 <211> LENGTH: 256 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 37 Met Thr Ala Pro Gly Ala Ala Gly Arg Cys Pro Pro Thr Thr Trp Leu 1 5 10 15 Gly Ser Leu Leu Leu Leu Val Cys Leu Leu Ala Ser Arg Ser Ile Thr 20 25 30 Glu Glu Val Ser Glu Tyr Cys Ser His Met Ile Gly Ser Gly His Leu 35 40 45 Gln Ser Leu Gln Arg Leu Ile Asp Ser Gln Met Glu Thr Ser Cys Gln 50 55 60 Ile Thr Phe Glu Phe Val Asp Gln Glu Gln Leu Lys Asp Pro Val Cys 65 70 75 80 Tyr Leu Lys Lys Ala Phe Leu Leu Val Gln Asp Ile Met Glu Asp Thr 85 90 95 Met Arg Phe Arg Asp Asn Thr Pro Asn Ala Ile Ala Ile Val Gln Leu 100 105 110 Gln Glu Leu Ser Leu Arg Leu Lys Ser Cys Phe Thr Lys Asp Tyr Glu 115 120 125 Glu His Asp Lys Ala Cys Val Arg Thr Phe Tyr Glu Thr Pro Leu Gln 130 135 140 Leu Leu Glu Lys Val Lys Asn Val Phe Asn Glu Thr Lys Asn Leu Leu 145 150 155 160 Asp Lys Asp Trp Asn Ile Phe Ser Lys Asn Cys Asn Asn Ser Phe Ala 165 170 175 Glu Cys Ser Ser Gln Gly His Glu Arg Gln Ser Glu Gly Ser Ser Ser 180 185 190 Pro Gln Leu Gln Glu Ser Val Phe His Leu Leu Val Pro Ser Val Ile 195 200 205 Leu Val Leu Leu Ala Val Gly Gly Leu Leu Phe Tyr Arg Trp Arg Arg 210 215 220 Arg Ser His Gln Glu Pro Gln Arg Ala Asp Ser Pro Leu Glu Gln Pro 225 230 235 240 Glu Gly Ser Pro Leu Thr Gln Asp Asp Arg Gln Val Glu Leu Pro Val 245 250 255 <210> SEQ ID NO 38 <211> LENGTH: 144 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 38 Met Trp Leu Gln Ser Leu Leu Leu Leu Gly Thr Val Ala Cys Ser Ile 1 5 10 15 Ser Ala Pro Ala Arg Ser Pro Ser Pro Ser Thr Gln Pro Trp Glu His 20 25 30 Val Asn Ala Ile Gln Glu Ala Arg Arg Leu Leu Asn Leu Ser Arg Asp 35 40 45 Thr Ala Ala Glu Met Asn Glu Thr Val Glu Val Ile Ser Glu Met Phe 50 55 60 Asp Leu Gln Glu Pro Thr Cys Leu Gln Thr Arg Leu Glu Leu Tyr Lys 65 70 75 80 Gln Gly Leu Arg Gly Ser Leu Thr Lys Leu Lys Gly Pro Leu Thr Met 85 90 95 Met Ala Ser His Tyr Lys Gln His Cys Pro Pro Thr Pro Glu Thr Ser 100 105 110 Cys Ala Thr Gln Ile Ile Thr Phe Glu Ser Phe Lys Glu Asn Leu Lys 115 120 125 Asp Phe Leu Leu Val Ile Pro Phe Asp Cys Trp Glu Pro Val Gln Glu 130 135 140 <210> SEQ ID NO 39 <211> LENGTH: 207 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 39 Met Ala Gly Pro Ala Thr Gln Ser Pro Met Lys Leu Met Ala Leu Gln 1 5 10 15 Leu Leu Leu Trp His Ser Ala Leu Trp Thr Val Gln Glu Ala Thr Pro 20 25 30 Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Cys Leu 35 40 45 Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys 50 55 60 Leu Val Ser Glu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu 65 70 75 80 Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser 85 90 95 Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His 100 105 110 Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile 115 120 125 Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala 130 135 140 Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala 145 150 155 160 Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala 165 170 175 Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser 180 185 190 Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro 195 200 205 <210> SEQ ID NO 40 <211> LENGTH: 204 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 40 Met Ala Gly Pro Ala Thr Gln Ser Pro Met Lys Leu Met Ala Leu Gln 1 5 10 15 Leu Leu Leu Trp His Ser Ala Leu Trp Thr Val Gln Glu Ala Thr Pro 20 25 30 Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Cys Leu 35 40 45 Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys 50 55 60 Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu 65 70 75 80 Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser 85 90 95 Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu 100 105 110 Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu 115 120 125 Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala 130 135 140 Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu 145 150 155 160 Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg 165 170 175 Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu 180 185 190 Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro 195 200 <210> SEQ ID NO 41 <211> LENGTH: 200 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 41 Met Ser Pro Glu Pro Ala Leu Ser Pro Ala Leu Gln Leu Leu Leu Trp 1 5 10 15 His Ser Ala Leu Trp Thr Val Gln Glu Ala Thr Pro Leu Gly Pro Ala 20 25 30 Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Cys Leu Glu Gln Val Arg 35 40 45 Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr 50 55 60 Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu 65 70 75 80 Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln 85 90 95 Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln 100 105 110 Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr 115 120 125 Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp 130 135 140 Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro Thr Gln 145 150 155 160 Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly 165 170 175 Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg 180 185 190 Val Leu Arg His Leu Ala Gln Pro 195 200 <210> SEQ ID NO 42 <211> LENGTH: 393 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 42 Met Glu Glu Pro Gln Ser Asp Pro Ser Val Glu Pro Pro Leu Ser Gln 1 5 10 15 Glu Thr Phe Ser Asp Leu Trp Lys Leu Leu Pro Glu Asn Asn Val Leu 20 25 30 Ser Pro Leu Pro Ser Gln Ala Met Asp Asp Leu Met Leu Ser Pro Asp 35 40 45 Asp Ile Glu Gln Trp Phe Thr Glu Asp Pro Gly Pro Asp Glu Ala Pro 50 55 60 Arg Met Pro Glu Ala Ala Pro Pro Val Ala Pro Ala Pro Ala Ala Pro 65 70 75 80 Thr Pro Ala Ala Pro Ala Pro Ala Pro Ser Trp Pro Leu Ser Ser Ser 85 90 95 Val Pro Ser Gln Lys Thr Tyr Gln Gly Ser Tyr Gly Phe Arg Leu Gly 100 105 110 Phe Leu His Ser Gly Thr Ala Lys Ser Val Thr Cys Thr Tyr Ser Pro 115 120 125 Ala Leu Asn Lys Met Phe Cys Gln Leu Ala Lys Thr Cys Pro Val Gln 130 135 140 Leu Trp Val Asp Ser Thr Pro Pro Pro Gly Thr Arg Val Arg Ala Met 145 150 155 160 Ala Ile Tyr Lys Gln Ser Gln His Met Thr Glu Val Val Arg Arg Cys 165 170 175 Pro His His Glu Arg Cys Ser Asp Ser Asp Gly Leu Ala Pro Pro Gln 180 185 190 His Leu Ile Arg Val Glu Gly Asn Leu Arg Val Glu Tyr Leu Asp Asp 195 200 205 Arg Asn Thr Phe Arg His Ser Val Val Val Pro Tyr Glu Pro Pro Glu 210 215 220 Val Gly Ser Asp Cys Thr Thr Ile His Tyr Asn Tyr Met Cys Asn Ser 225 230 235 240 Ser Cys Met Gly Gly Met Asn Arg Arg Pro Ile Leu Thr Ile Ile Thr 245 250 255 Leu Glu Asp Ser Ser Gly Asn Leu Leu Gly Arg Asn Ser Phe Glu Val 260 265 270 Arg Val Cys Ala Cys Pro Gly Arg Asp Arg Arg Thr Glu Glu Glu Asn 275 280 285 Leu Arg Lys Lys Gly Glu Pro His His Glu Leu Pro Pro Gly Ser Thr 290 295 300 Lys Arg Ala Leu Pro Asn Asn Thr Ser Ser Ser Pro Gln Pro Lys Lys 305 310 315 320 Lys Pro Leu Asp Gly Glu Tyr Phe Thr Leu Gln Ile Arg Gly Arg Glu 325 330 335 Arg Phe Glu Met Phe Arg Glu Leu Asn Glu Ala Leu Glu Leu Lys Asp 340 345 350 Ala Gln Ala Gly Lys Glu Pro Gly Gly Ser Arg Ala His Ser Ser His 355 360 365 Leu Lys Ser Lys Lys Gly Gln Ser Thr Ser Arg His Lys Lys Leu Met 370 375 380 Phe Lys Thr Glu Gly Pro Asp Ser Asp 385 390 <210> SEQ ID NO 43 <211> LENGTH: 393 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 43 Met Glu Glu Pro Gln Ser Asp Pro Ser Val Glu Pro Pro Leu Ser Gln 1 5 10 15 Glu Thr Phe Ser Asp Leu Trp Lys Leu Leu Pro Glu Asn Asn Val Leu 20 25 30 Ser Pro Leu Pro Ser Gln Ala Met Asp Asp Leu Met Leu Ser Pro Asp 35 40 45 Asp Ile Glu Gln Trp Phe Thr Glu Asp Pro Gly Pro Asp Glu Ala Pro 50 55 60 Arg Met Pro Glu Ala Ala Pro Pro Val Ala Pro Ala Pro Ala Ala Pro 65 70 75 80 Thr Pro Ala Ala Pro Ala Pro Ala Pro Ser Trp Pro Leu Ser Ser Ser 85 90 95 Val Pro Ser Gln Lys Thr Tyr Gln Gly Ser Tyr Gly Phe Arg Leu Gly 100 105 110 Phe Leu His Ser Gly Thr Ala Lys Ser Val Thr Cys Thr Tyr Ser Pro 115 120 125 Ala Leu Asn Lys Met Phe Cys Gln Leu Ala Lys Thr Cys Pro Val Gln 130 135 140 Leu Trp Val Asp Ser Thr Pro Pro Pro Gly Thr Arg Val Arg Ala Met 145 150 155 160 Ala Ile Tyr Lys Gln Ser Gln His Met Thr Glu Val Val Arg Arg Cys 165 170 175 Pro His His Glu Arg Cys Ser Asp Ser Asp Gly Leu Ala Pro Pro Gln 180 185 190 His Leu Ile Arg Val Glu Gly Asn Leu Arg Val Glu Tyr Leu Asp Asp 195 200 205 Arg Asn Thr Phe Arg His Ser Val Val Val Pro Tyr Glu Pro Pro Glu 210 215 220 Val Gly Ser Asp Cys Thr Thr Ile His Tyr Asn Tyr Met Cys Asn Ser 225 230 235 240 Ser Cys Met Gly Gly Met Asn Arg Arg Pro Ile Leu Thr Ile Ile Thr 245 250 255 Leu Glu Asp Ser Ser Gly Asn Leu Leu Gly Arg Asn Ser Phe Glu Val 260 265 270 Arg Val Cys Ala Cys Pro Gly Arg Asp Arg Arg Thr Glu Glu Glu Asn 275 280 285 Leu Arg Lys Lys Gly Glu Pro His His Glu Leu Pro Pro Gly Ser Thr 290 295 300 Lys Arg Ala Leu Pro Asn Asn Thr Ser Ser Ser Pro Gln Pro Lys Lys 305 310 315 320 Lys Pro Leu Asp Gly Glu Tyr Phe Thr Leu Gln Ile Arg Gly Arg Glu 325 330 335 Arg Phe Glu Met Phe Arg Glu Leu Asn Glu Ala Leu Glu Leu Lys Asp 340 345 350 Ala Gln Ala Gly Lys Glu Pro Gly Gly Ser Arg Ala His Ser Ser His 355 360 365 Leu Lys Ser Lys Lys Gly Gln Ser Thr Ser Arg His Lys Lys Leu Met 370 375 380 Phe Lys Thr Glu Gly Pro Asp Ser Asp 385 390 <210> SEQ ID NO 44 <211> LENGTH: 341 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 44 Met Glu Glu Pro Gln Ser Asp Pro Ser Val Glu Pro Pro Leu Ser Gln 1 5 10 15 Glu Thr Phe Ser Asp Leu Trp Lys Leu Leu Pro Glu Asn Asn Val Leu 20 25 30 Ser Pro Leu Pro Ser Gln Ala Met Asp Asp Leu Met Leu Ser Pro Asp 35 40 45 Asp Ile Glu Gln Trp Phe Thr Glu Asp Pro Gly Pro Asp Glu Ala Pro 50 55 60 Arg Met Pro Glu Ala Ala Pro Pro Val Ala Pro Ala Pro Ala Ala Pro 65 70 75 80 Thr Pro Ala Ala Pro Ala Pro Ala Pro Ser Trp Pro Leu Ser Ser Ser 85 90 95 Val Pro Ser Gln Lys Thr Tyr Gln Gly Ser Tyr Gly Phe Arg Leu Gly 100 105 110 Phe Leu His Ser Gly Thr Ala Lys Ser Val Thr Cys Thr Tyr Ser Pro 115 120 125 Ala Leu Asn Lys Met Phe Cys Gln Leu Ala Lys Thr Cys Pro Val Gln 130 135 140 Leu Trp Val Asp Ser Thr Pro Pro Pro Gly Thr Arg Val Arg Ala Met 145 150 155 160 Ala Ile Tyr Lys Gln Ser Gln His Met Thr Glu Val Val Arg Arg Cys 165 170 175 Pro His His Glu Arg Cys Ser Asp Ser Asp Gly Leu Ala Pro Pro Gln 180 185 190 His Leu Ile Arg Val Glu Gly Asn Leu Arg Val Glu Tyr Leu Asp Asp 195 200 205 Arg Asn Thr Phe Arg His Ser Val Val Val Pro Tyr Glu Pro Pro Glu 210 215 220 Val Gly Ser Asp Cys Thr Thr Ile His Tyr Asn Tyr Met Cys Asn Ser 225 230 235 240 Ser Cys Met Gly Gly Met Asn Arg Arg Pro Ile Leu Thr Ile Ile Thr 245 250 255 Leu Glu Asp Ser Ser Gly Asn Leu Leu Gly Arg Asn Ser Phe Glu Val 260 265 270 Arg Val Cys Ala Cys Pro Gly Arg Asp Arg Arg Thr Glu Glu Glu Asn 275 280 285 Leu Arg Lys Lys Gly Glu Pro His His Glu Leu Pro Pro Gly Ser Thr 290 295 300 Lys Arg Ala Leu Pro Asn Asn Thr Ser Ser Ser Pro Gln Pro Lys Lys 305 310 315 320 Lys Pro Leu Asp Gly Glu Tyr Phe Thr Leu Gln Asp Gln Thr Ser Phe 325 330 335 Gln Lys Glu Asn Cys 340 <210> SEQ ID NO 45 <211> LENGTH: 346 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 45 Met Glu Glu Pro Gln Ser Asp Pro Ser Val Glu Pro Pro Leu Ser Gln 1 5 10 15 Glu Thr Phe Ser Asp Leu Trp Lys Leu Leu Pro Glu Asn Asn Val Leu 20 25 30 Ser Pro Leu Pro Ser Gln Ala Met Asp Asp Leu Met Leu Ser Pro Asp 35 40 45 Asp Ile Glu Gln Trp Phe Thr Glu Asp Pro Gly Pro Asp Glu Ala Pro 50 55 60 Arg Met Pro Glu Ala Ala Pro Pro Val Ala Pro Ala Pro Ala Ala Pro 65 70 75 80 Thr Pro Ala Ala Pro Ala Pro Ala Pro Ser Trp Pro Leu Ser Ser Ser 85 90 95 Val Pro Ser Gln Lys Thr Tyr Gln Gly Ser Tyr Gly Phe Arg Leu Gly 100 105 110 Phe Leu His Ser Gly Thr Ala Lys Ser Val Thr Cys Thr Tyr Ser Pro 115 120 125 Ala Leu Asn Lys Met Phe Cys Gln Leu Ala Lys Thr Cys Pro Val Gln 130 135 140 Leu Trp Val Asp Ser Thr Pro Pro Pro Gly Thr Arg Val Arg Ala Met 145 150 155 160 Ala Ile Tyr Lys Gln Ser Gln His Met Thr Glu Val Val Arg Arg Cys 165 170 175 Pro His His Glu Arg Cys Ser Asp Ser Asp Gly Leu Ala Pro Pro Gln 180 185 190 His Leu Ile Arg Val Glu Gly Asn Leu Arg Val Glu Tyr Leu Asp Asp 195 200 205 Arg Asn Thr Phe Arg His Ser Val Val Val Pro Tyr Glu Pro Pro Glu 210 215 220 Val Gly Ser Asp Cys Thr Thr Ile His Tyr Asn Tyr Met Cys Asn Ser 225 230 235 240 Ser Cys Met Gly Gly Met Asn Arg Arg Pro Ile Leu Thr Ile Ile Thr 245 250 255 Leu Glu Asp Ser Ser Gly Asn Leu Leu Gly Arg Asn Ser Phe Glu Val 260 265 270 Arg Val Cys Ala Cys Pro Gly Arg Asp Arg Arg Thr Glu Glu Glu Asn 275 280 285 Leu Arg Lys Lys Gly Glu Pro His His Glu Leu Pro Pro Gly Ser Thr 290 295 300 Lys Arg Ala Leu Pro Asn Asn Thr Ser Ser Ser Pro Gln Pro Lys Lys 305 310 315 320 Lys Pro Leu Asp Gly Glu Tyr Phe Thr Leu Gln Met Leu Leu Asp Leu 325 330 335 Arg Trp Cys Tyr Phe Leu Ile Asn Ser Ser 340 345 <210> SEQ ID NO 46 <211> LENGTH: 261 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 46 Met Phe Cys Gln Leu Ala Lys Thr Cys Pro Val Gln Leu Trp Val Asp 1 5 10 15 Ser Thr Pro Pro Pro Gly Thr Arg Val Arg Ala Met Ala Ile Tyr Lys 20 25 30 Gln Ser Gln His Met Thr Glu Val Val Arg Arg Cys Pro His His Glu 35 40 45 Arg Cys Ser Asp Ser Asp Gly Leu Ala Pro Pro Gln His Leu Ile Arg 50 55 60 Val Glu Gly Asn Leu Arg Val Glu Tyr Leu Asp Asp Arg Asn Thr Phe 65 70 75 80 Arg His Ser Val Val Val Pro Tyr Glu Pro Pro Glu Val Gly Ser Asp 85 90 95 Cys Thr Thr Ile His Tyr Asn Tyr Met Cys Asn Ser Ser Cys Met Gly 100 105 110 Gly Met Asn Arg Arg Pro Ile Leu Thr Ile Ile Thr Leu Glu Asp Ser 115 120 125 Ser Gly Asn Leu Leu Gly Arg Asn Ser Phe Glu Val Arg Val Cys Ala 130 135 140 Cys Pro Gly Arg Asp Arg Arg Thr Glu Glu Glu Asn Leu Arg Lys Lys 145 150 155 160 Gly Glu Pro His His Glu Leu Pro Pro Gly Ser Thr Lys Arg Ala Leu 165 170 175 Pro Asn Asn Thr Ser Ser Ser Pro Gln Pro Lys Lys Lys Pro Leu Asp 180 185 190 Gly Glu Tyr Phe Thr Leu Gln Ile Arg Gly Arg Glu Arg Phe Glu Met 195 200 205 Phe Arg Glu Leu Asn Glu Ala Leu Glu Leu Lys Asp Ala Gln Ala Gly 210 215 220 Lys Glu Pro Gly Gly Ser Arg Ala His Ser Ser His Leu Lys Ser Lys 225 230 235 240 Lys Gly Gln Ser Thr Ser Arg His Lys Lys Leu Met Phe Lys Thr Glu 245 250 255 Gly Pro Asp Ser Asp 260 <210> SEQ ID NO 47 <211> LENGTH: 209 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 47 Met Phe Cys Gln Leu Ala Lys Thr Cys Pro Val Gln Leu Trp Val Asp 1 5 10 15 Ser Thr Pro Pro Pro Gly Thr Arg Val Arg Ala Met Ala Ile Tyr Lys 20 25 30 Gln Ser Gln His Met Thr Glu Val Val Arg Arg Cys Pro His His Glu 35 40 45 Arg Cys Ser Asp Ser Asp Gly Leu Ala Pro Pro Gln His Leu Ile Arg 50 55 60 Val Glu Gly Asn Leu Arg Val Glu Tyr Leu Asp Asp Arg Asn Thr Phe 65 70 75 80 Arg His Ser Val Val Val Pro Tyr Glu Pro Pro Glu Val Gly Ser Asp 85 90 95 Cys Thr Thr Ile His Tyr Asn Tyr Met Cys Asn Ser Ser Cys Met Gly 100 105 110 Gly Met Asn Arg Arg Pro Ile Leu Thr Ile Ile Thr Leu Glu Asp Ser 115 120 125 Ser Gly Asn Leu Leu Gly Arg Asn Ser Phe Glu Val Arg Val Cys Ala 130 135 140 Cys Pro Gly Arg Asp Arg Arg Thr Glu Glu Glu Asn Leu Arg Lys Lys 145 150 155 160 Gly Glu Pro His His Glu Leu Pro Pro Gly Ser Thr Lys Arg Ala Leu 165 170 175 Pro Asn Asn Thr Ser Ser Ser Pro Gln Pro Lys Lys Lys Pro Leu Asp 180 185 190 Gly Glu Tyr Phe Thr Leu Gln Asp Gln Thr Ser Phe Gln Lys Glu Asn 195 200 205 Cys <210> SEQ ID NO 48 <211> LENGTH: 214 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 48 Met Phe Cys Gln Leu Ala Lys Thr Cys Pro Val Gln Leu Trp Val Asp 1 5 10 15 Ser Thr Pro Pro Pro Gly Thr Arg Val Arg Ala Met Ala Ile Tyr Lys 20 25 30 Gln Ser Gln His Met Thr Glu Val Val Arg Arg Cys Pro His His Glu 35 40 45 Arg Cys Ser Asp Ser Asp Gly Leu Ala Pro Pro Gln His Leu Ile Arg 50 55 60 Val Glu Gly Asn Leu Arg Val Glu Tyr Leu Asp Asp Arg Asn Thr Phe 65 70 75 80 Arg His Ser Val Val Val Pro Tyr Glu Pro Pro Glu Val Gly Ser Asp 85 90 95 Cys Thr Thr Ile His Tyr Asn Tyr Met Cys Asn Ser Ser Cys Met Gly 100 105 110 Gly Met Asn Arg Arg Pro Ile Leu Thr Ile Ile Thr Leu Glu Asp Ser 115 120 125 Ser Gly Asn Leu Leu Gly Arg Asn Ser Phe Glu Val Arg Val Cys Ala 130 135 140 Cys Pro Gly Arg Asp Arg Arg Thr Glu Glu Glu Asn Leu Arg Lys Lys 145 150 155 160 Gly Glu Pro His His Glu Leu Pro Pro Gly Ser Thr Lys Arg Ala Leu 165 170 175 Pro Asn Asn Thr Ser Ser Ser Pro Gln Pro Lys Lys Lys Pro Leu Asp 180 185 190 Gly Glu Tyr Phe Thr Leu Gln Met Leu Leu Asp Leu Arg Trp Cys Tyr 195 200 205 Phe Leu Ile Asn Ser Ser 210 <210> SEQ ID NO 49 <211> LENGTH: 1237 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 49 Met Asp Ala Lys Ala Arg Asn Cys Leu Leu Gln His Arg Glu Ala Leu 1 5 10 15 Glu Lys Asp Ile Lys Thr Ser Tyr Ile Met Asp His Met Ile Ser Asp 20 25 30 Gly Phe Leu Thr Ile Ser Glu Glu Glu Lys Val Arg Asn Glu Pro Thr 35 40 45 Gln Gln Gln Arg Ala Ala Met Leu Ile Lys Met Ile Leu Lys Lys Asp 50 55 60 Asn Asp Ser Tyr Val Ser Phe Tyr Asn Ala Leu Leu His Glu Gly Tyr 65 70 75 80 Lys Asp Leu Ala Ala Leu Leu His Asp Gly Ile Pro Val Val Ser Ser 85 90 95 Ser Ser Val Arg Thr Val Leu Cys Glu Gly Gly Val Pro Gln Arg Pro 100 105 110 Val Val Phe Val Thr Arg Lys Lys Leu Val Asn Ala Ile Gln Gln Lys 115 120 125 Leu Ser Lys Leu Lys Gly Glu Pro Gly Trp Val Thr Ile His Gly Met 130 135 140 Ala Gly Cys Gly Lys Ser Val Leu Ala Ala Glu Ala Val Arg Asp His 145 150 155 160 Ser Leu Leu Glu Gly Cys Phe Pro Gly Gly Val His Trp Val Ser Val 165 170 175 Gly Lys Gln Asp Lys Ser Gly Leu Leu Met Lys Leu Gln Asn Leu Cys 180 185 190 Thr Arg Leu Asp Gln Asp Glu Ser Phe Ser Gln Arg Leu Pro Leu Asn 195 200 205 Ile Glu Glu Ala Lys Asp Arg Leu Arg Ile Leu Met Leu Arg Lys His 210 215 220 Pro Arg Ser Leu Leu Ile Leu Asp Asp Val Trp Asp Ser Trp Val Leu 225 230 235 240 Lys Ala Phe Asp Ser Gln Cys Gln Ile Leu Leu Thr Thr Arg Asp Lys 245 250 255 Ser Val Thr Asp Ser Val Met Gly Pro Lys Tyr Val Val Pro Val Glu 260 265 270 Ser Ser Leu Gly Lys Glu Lys Gly Leu Glu Ile Leu Ser Leu Phe Val 275 280 285 Asn Met Lys Lys Ala Asp Leu Pro Glu Gln Ala His Ser Ile Ile Lys 290 295 300 Glu Cys Lys Gly Ser Pro Leu Val Val Ser Leu Ile Gly Ala Leu Leu 305 310 315 320 Arg Asp Phe Pro Asn Arg Trp Glu Tyr Tyr Leu Lys Gln Leu Gln Asn 325 330 335 Lys Gln Phe Lys Arg Ile Arg Lys Ser Ser Ser Tyr Asp Tyr Glu Ala 340 345 350 Leu Asp Glu Ala Met Ser Ile Ser Val Glu Met Leu Arg Glu Asp Ile 355 360 365 Lys Asp Tyr Tyr Thr Asp Leu Ser Ile Leu Gln Lys Asp Val Lys Val 370 375 380 Pro Thr Lys Val Leu Cys Ile Leu Trp Asp Met Glu Thr Glu Glu Val 385 390 395 400 Glu Asp Ile Leu Gln Glu Phe Val Asn Lys Ser Leu Leu Phe Cys Asp 405 410 415 Arg Asn Gly Lys Ser Phe Arg Tyr Tyr Leu His Asp Leu Gln Val Asp 420 425 430 Phe Leu Thr Glu Lys Asn Cys Ser Gln Leu Gln Asp Leu His Lys Lys 435 440 445 Ile Ile Thr Gln Phe Gln Arg Tyr His Gln Pro His Thr Leu Ser Pro 450 455 460 Asp Gln Glu Asp Cys Met Tyr Trp Tyr Asn Phe Leu Ala Tyr His Met 465 470 475 480 Ala Ser Ala Lys Met His Lys Glu Leu Cys Ala Leu Met Phe Ser Leu 485 490 495 Asp Trp Ile Lys Ala Lys Thr Glu Leu Val Gly Pro Ala His Leu Ile 500 505 510 His Glu Phe Val Glu Tyr Arg His Ile Leu Asp Glu Lys Asp Cys Ala 515 520 525 Val Ser Glu Asn Phe Gln Glu Phe Leu Ser Leu Asn Gly His Leu Leu 530 535 540 Gly Arg Gln Pro Phe Pro Asn Ile Val Gln Leu Gly Leu Cys Glu Pro 545 550 555 560 Glu Thr Ser Glu Val Tyr Gln Gln Ala Lys Leu Gln Ala Lys Gln Glu 565 570 575 Val Asp Asn Gly Met Leu Tyr Leu Glu Trp Ile Asn Lys Lys Asn Ile 580 585 590 Thr Asn Leu Ser Arg Leu Val Val Arg Pro His Thr Asp Ala Val Tyr 595 600 605 His Ala Cys Phe Ser Glu Asp Gly Gln Arg Ile Ala Ser Cys Gly Ala 610 615 620 Asp Lys Thr Leu Gln Val Phe Lys Ala Glu Thr Gly Glu Lys Leu Leu 625 630 635 640 Glu Ile Lys Ala His Glu Asp Glu Val Leu Cys Cys Ala Phe Ser Thr 645 650 655 Asp Asp Arg Phe Ile Ala Thr Cys Ser Val Asp Lys Lys Val Lys Ile 660 665 670 Trp Asn Ser Met Thr Gly Glu Leu Val His Thr Tyr Asp Glu His Ser 675 680 685 Glu Gln Val Asn Cys Cys His Phe Thr Asn Ser Ser His His Leu Leu 690 695 700 Leu Ala Thr Gly Ser Ser Asp Cys Phe Leu Lys Leu Trp Asp Leu Asn 705 710 715 720 Gln Lys Glu Cys Arg Asn Thr Met Phe Gly His Thr Asn Ser Val Asn 725 730 735 His Cys Arg Phe Ser Pro Asp Asp Lys Leu Leu Ala Ser Cys Ser Ala 740 745 750 Asp Gly Thr Leu Lys Leu Trp Asp Ala Thr Ser Ala Asn Glu Arg Lys 755 760 765 Ser Ile Asn Val Lys Gln Phe Phe Leu Asn Leu Glu Asp Pro Gln Glu 770 775 780 Asp Met Glu Val Ile Val Lys Cys Cys Ser Trp Ser Ala Asp Gly Ala 785 790 795 800 Arg Ile Met Val Ala Ala Lys Asn Lys Ile Phe Leu Phe Asp Ile His 805 810 815 Thr Ser Gly Leu Leu Gly Glu Ile His Thr Gly His His Ser Thr Ile 820 825 830 Gln Tyr Cys Asp Phe Ser Pro Gln Asn His Leu Ala Val Val Ala Leu 835 840 845 Ser Gln Tyr Cys Val Glu Leu Trp Asn Thr Asp Ser Arg Ser Lys Val 850 855 860 Ala Asp Cys Arg Gly His Leu Ser Trp Val His Gly Val Met Phe Ser 865 870 875 880 Pro Asp Gly Ser Ser Phe Leu Thr Ser Ser Asp Asp Gln Thr Ile Arg 885 890 895 Leu Trp Glu Thr Lys Lys Val Cys Lys Asn Ser Ala Val Met Leu Lys 900 905 910 Gln Glu Val Asp Val Val Phe Gln Glu Asn Glu Val Met Val Leu Ala 915 920 925 Val Asp His Ile Arg Arg Leu Gln Leu Ile Asn Gly Arg Thr Gly Gln 930 935 940 Ile Asp Tyr Leu Thr Glu Ala Gln Val Ser Cys Cys Cys Leu Ser Pro 945 950 955 960 His Leu Gln Tyr Ile Ala Phe Gly Asp Glu Asn Gly Ala Ile Glu Ile 965 970 975 Leu Glu Leu Val Asn Asn Arg Ile Phe Gln Ser Arg Phe Gln His Lys 980 985 990 Lys Thr Val Trp His Ile Gln Phe Thr Ala Asp Glu Lys Thr Leu Ile 995 1000 1005 Ser Ser Ser Asp Asp Ala Glu Ile Gln Val Trp Asn Trp Gln Leu Asp 1010 1015 1020 Lys Cys Ile Phe Leu Arg Gly His Gln Glu Thr Val Lys Asp Phe Arg 1025 1030 1035 1040 Leu Leu Lys Asn Ser Arg Leu Leu Ser Trp Ser Phe Asp Gly Thr Val 1045 1050 1055 Lys Val Trp Asn Ile Ile Thr Gly Asn Lys Glu Lys Asp Phe Val Cys 1060 1065 1070 His Gln Gly Thr Val Leu Ser Cys Asp Ile Ser His Asp Ala Thr Lys 1075 1080 1085 Phe Ser Ser Thr Ser Ala Asp Lys Thr Ala Lys Ile Trp Ser Phe Asp 1090 1095 1100 Leu Leu Leu Pro Leu His Glu Leu Arg Gly His Asn Gly Cys Val Arg 1105 1110 1115 1120 Cys Ser Ala Phe Ser Val Asp Ser Thr Leu Leu Ala Thr Gly Asp Asp 1125 1130 1135 Asn Gly Glu Ile Arg Ile Trp Asn Val Ser Asn Gly Glu Leu Leu His 1140 1145 1150 Leu Cys Ala Pro Leu Ser Glu Glu Gly Ala Ala Thr His Gly Gly Trp 1155 1160 1165 Val Thr Asp Leu Cys Phe Ser Pro Asp Gly Lys Met Leu Ile Ser Ala 1170 1175 1180 Gly Gly Tyr Ile Lys Trp Trp Asn Val Val Thr Gly Glu Ser Ser Gln 1185 1190 1195 1200 Thr Phe Tyr Thr Asn Gly Thr Asn Leu Lys Lys Ile His Val Ser Pro 1205 1210 1215 Asp Phe Lys Thr Tyr Val Thr Val Asp Asn Leu Gly Ile Leu Tyr Ile 1220 1225 1230 Leu Gln Thr Leu Glu 1235 <210> SEQ ID NO 50 <211> LENGTH: 1194 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 50 Met Asp Ala Lys Ala Arg Asn Cys Leu Leu Gln His Arg Glu Ala Leu 1 5 10 15 Glu Lys Asp Ile Lys Thr Ser Tyr Ile Met Asp His Met Ile Ser Asp 20 25 30 Gly Phe Leu Thr Ile Ser Glu Glu Glu Lys Val Arg Asn Glu Pro Thr 35 40 45 Gln Gln Gln Arg Ala Ala Met Leu Ile Lys Met Ile Leu Lys Lys Asp 50 55 60 Asn Asp Ser Tyr Val Ser Phe Tyr Asn Ala Leu Leu His Glu Gly Tyr 65 70 75 80 Lys Asp Leu Ala Ala Leu Leu His Asp Gly Ile Pro Val Val Ser Ser 85 90 95 Ser Ser Val Arg Thr Val Leu Cys Glu Gly Gly Val Pro Gln Arg Pro 100 105 110 Val Val Phe Val Thr Arg Lys Lys Leu Val Asn Ala Ile Gln Gln Lys 115 120 125 Leu Ser Lys Leu Lys Gly Glu Pro Gly Trp Val Thr Ile His Gly Met 130 135 140 Ala Gly Cys Gly Lys Ser Val Leu Ala Ala Glu Ala Val Arg Asp His 145 150 155 160 Ser Leu Leu Glu Gly Cys Phe Pro Gly Gly Val His Trp Val Ser Val 165 170 175 Gly Lys Gln Asp Lys Ser Gly Leu Leu Met Lys Leu Gln Asn Leu Cys 180 185 190 Thr Arg Leu Asp Gln Asp Glu Ser Phe Ser Gln Arg Leu Pro Leu Asn 195 200 205 Ile Glu Glu Ala Lys Asp Arg Leu Arg Ile Leu Met Leu Arg Lys His 210 215 220 Pro Arg Ser Leu Leu Ile Leu Asp Asp Val Trp Asp Ser Trp Val Leu 225 230 235 240 Lys Ala Phe Asp Ser Gln Cys Gln Ile Leu Leu Thr Thr Arg Asp Lys 245 250 255 Ser Val Thr Asp Ser Val Met Gly Pro Lys Tyr Val Val Pro Val Glu 260 265 270 Ser Ser Leu Gly Lys Glu Lys Gly Leu Glu Ile Leu Ser Leu Phe Val 275 280 285 Asn Met Lys Lys Ala Asp Leu Pro Glu Gln Ala His Ser Ile Ile Lys 290 295 300 Glu Cys Lys Gly Ser Pro Leu Val Val Ser Leu Ile Gly Ala Leu Leu 305 310 315 320 Arg Asp Phe Pro Asn Arg Trp Glu Tyr Tyr Leu Lys Gln Leu Gln Asn 325 330 335 Lys Gln Phe Lys Arg Ile Arg Lys Ser Ser Ser Tyr Asp Tyr Glu Ala 340 345 350 Leu Asp Glu Ala Met Ser Ile Ser Val Glu Met Leu Arg Glu Asp Ile 355 360 365 Lys Asp Tyr Tyr Thr Asp Leu Ser Ile Leu Gln Lys Asp Val Lys Val 370 375 380 Pro Thr Lys Val Leu Cys Ile Leu Trp Asp Met Glu Thr Glu Glu Val 385 390 395 400 Glu Asp Ile Leu Gln Glu Phe Val Asn Lys Ser Leu Leu Phe Cys Asp 405 410 415 Arg Asn Gly Lys Ser Phe Arg Tyr Tyr Leu His Asp Leu Gln Val Asp 420 425 430 Phe Leu Thr Glu Lys Asn Cys Ser Gln Leu Gln Asp Leu His Lys Lys 435 440 445 Ile Ile Thr Gln Phe Gln Arg Tyr His Gln Pro His Thr Leu Ser Pro 450 455 460 Asp Gln Glu Asp Cys Met Tyr Trp Tyr Asn Phe Leu Ala Tyr His Met 465 470 475 480 Ala Ser Ala Lys Met His Lys Glu Leu Cys Ala Leu Met Phe Ser Leu 485 490 495 Asp Trp Ile Lys Ala Lys Thr Glu Leu Val Gly Pro Ala His Leu Ile 500 505 510 His Glu Phe Val Glu Tyr Arg His Ile Leu Asp Glu Lys Asp Cys Ala 515 520 525 Val Ser Glu Asn Phe Gln Glu Phe Leu Ser Leu Asn Gly His Leu Leu 530 535 540 Gly Arg Gln Pro Phe Pro Asn Ile Val Gln Leu Gly Leu Cys Glu Pro 545 550 555 560 Glu Thr Ser Glu Val Tyr Gln Gln Ala Lys Leu Gln Ala Lys Gln Glu 565 570 575 Val Asp Asn Gly Met Leu Tyr Leu Glu Trp Ile Asn Lys Lys Asn Ile 580 585 590 Thr Asn Leu Ser Arg Leu Val Val Arg Pro His Thr Asp Ala Val Tyr 595 600 605 His Ala Cys Phe Ser Glu Asp Gly Gln Arg Ile Ala Ser Cys Gly Ala 610 615 620 Asp Lys Thr Leu Gln Val Phe Lys Ala Glu Thr Gly Glu Lys Leu Leu 625 630 635 640 Glu Ile Lys Ala His Glu Asp Glu Val Leu Cys Cys Ala Phe Ser Thr 645 650 655 Asp Asp Arg Phe Ile Ala Thr Cys Ser Val Asp Lys Lys Val Lys Ile 660 665 670 Trp Asn Ser Met Thr Gly Glu Leu Val His Thr Tyr Asp Glu His Ser 675 680 685 Glu Gln Val Asn Cys Cys His Phe Thr Asn Ser Ser His His Leu Leu 690 695 700 Leu Ala Thr Gly Ser Ser Asp Cys Phe Leu Lys Leu Trp Asp Leu Asn 705 710 715 720 Gln Lys Glu Cys Arg Asn Thr Met Phe Gly His Thr Asn Ser Val Asn 725 730 735 His Cys Arg Phe Ser Pro Asp Asp Lys Leu Leu Ala Ser Cys Ser Ala 740 745 750 Asp Gly Thr Leu Lys Leu Trp Asp Ala Thr Ser Ala Asn Glu Arg Lys 755 760 765 Ser Ile Asn Val Lys Gln Phe Phe Leu Asn Leu Glu Asp Pro Gln Glu 770 775 780 Asp Met Glu Val Ile Val Lys Cys Cys Ser Trp Ser Ala Asp Gly Ala 785 790 795 800 Arg Ile Met Val Ala Ala Lys Asn Lys Ile Phe Leu Trp Asn Thr Asp 805 810 815 Ser Arg Ser Lys Val Ala Asp Cys Arg Gly His Leu Ser Trp Val His 820 825 830 Gly Val Met Phe Ser Pro Asp Gly Ser Ser Phe Leu Thr Ser Ser Asp 835 840 845 Asp Gln Thr Ile Arg Leu Trp Glu Thr Lys Lys Val Cys Lys Asn Ser 850 855 860 Ala Val Met Leu Lys Gln Glu Val Asp Val Val Phe Gln Glu Asn Glu 865 870 875 880 Val Met Val Leu Ala Val Asp His Ile Arg Arg Leu Gln Leu Ile Asn 885 890 895 Gly Arg Thr Gly Gln Ile Asp Tyr Leu Thr Glu Ala Gln Val Ser Cys 900 905 910 Cys Cys Leu Ser Pro His Leu Gln Tyr Ile Ala Phe Gly Asp Glu Asn 915 920 925 Gly Ala Ile Glu Ile Leu Glu Leu Val Asn Asn Arg Ile Phe Gln Ser 930 935 940 Arg Phe Gln His Lys Lys Thr Val Trp His Ile Gln Phe Thr Ala Asp 945 950 955 960 Glu Lys Thr Leu Ile Ser Ser Ser Asp Asp Ala Glu Ile Gln Val Trp 965 970 975 Asn Trp Gln Leu Asp Lys Cys Ile Phe Leu Arg Gly His Gln Glu Thr 980 985 990 Val Lys Asp Phe Arg Leu Leu Lys Asn Ser Arg Leu Leu Ser Trp Ser 995 1000 1005 Phe Asp Gly Thr Val Lys Val Trp Asn Ile Ile Thr Gly Asn Lys Glu 1010 1015 1020 Lys Asp Phe Val Cys His Gln Gly Thr Val Leu Ser Cys Asp Ile Ser 1025 1030 1035 1040 His Asp Ala Thr Lys Phe Ser Ser Thr Ser Ala Asp Lys Thr Ala Lys 1045 1050 1055 Ile Trp Ser Phe Asp Leu Leu Leu Pro Leu His Glu Leu Arg Gly His 1060 1065 1070 Asn Gly Cys Val Arg Cys Ser Ala Phe Ser Val Asp Ser Thr Leu Leu 1075 1080 1085 Ala Thr Gly Asp Asp Asn Gly Glu Ile Arg Ile Trp Asn Val Ser Asn 1090 1095 1100 Gly Glu Leu Leu His Leu Cys Ala Pro Leu Ser Glu Glu Gly Ala Ala 1105 1110 1115 1120 Thr His Gly Gly Trp Val Thr Asp Leu Cys Phe Ser Pro Asp Gly Lys 1125 1130 1135 Met Leu Ile Ser Ala Gly Gly Tyr Ile Lys Trp Trp Asn Val Val Thr 1140 1145 1150 Gly Glu Ser Ser Gln Thr Phe Tyr Thr Asn Gly Thr Asn Leu Lys Lys 1155 1160 1165 Ile His Val Ser Pro Asp Phe Lys Thr Tyr Val Thr Val Asp Asn Leu 1170 1175 1180 Gly Ile Leu Tyr Ile Leu Gln Thr Leu Glu 1185 1190 <210> SEQ ID NO 51 <211> LENGTH: 1248 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 51 Met Asp Ala Lys Ala Arg Asn Cys Leu Leu Gln His Arg Glu Ala Leu 1 5 10 15 Glu Lys Asp Ile Lys Thr Ser Tyr Ile Met Asp His Met Ile Ser Asp 20 25 30 Gly Phe Leu Thr Ile Ser Glu Glu Glu Lys Val Arg Asn Glu Pro Thr 35 40 45 Gln Gln Gln Arg Ala Ala Met Leu Ile Lys Met Ile Leu Lys Lys Asp 50 55 60 Asn Asp Ser Tyr Val Ser Phe Tyr Asn Ala Leu Leu His Glu Gly Tyr 65 70 75 80 Lys Asp Leu Ala Ala Leu Leu His Asp Gly Ile Pro Val Val Ser Ser 85 90 95 Ser Ser Gly Lys Asp Ser Val Ser Gly Ile Thr Ser Tyr Val Arg Thr 100 105 110 Val Leu Cys Glu Gly Gly Val Pro Gln Arg Pro Val Val Phe Val Thr 115 120 125 Arg Lys Lys Leu Val Asn Ala Ile Gln Gln Lys Leu Ser Lys Leu Lys 130 135 140 Gly Glu Pro Gly Trp Val Thr Ile His Gly Met Ala Gly Cys Gly Lys 145 150 155 160 Ser Val Leu Ala Ala Glu Ala Val Arg Asp His Ser Leu Leu Glu Gly 165 170 175 Cys Phe Pro Gly Gly Val His Trp Val Ser Val Gly Lys Gln Asp Lys 180 185 190 Ser Gly Leu Leu Met Lys Leu Gln Asn Leu Cys Thr Arg Leu Asp Gln 195 200 205 Asp Glu Ser Phe Ser Gln Arg Leu Pro Leu Asn Ile Glu Glu Ala Lys 210 215 220 Asp Arg Leu Arg Ile Leu Met Leu Arg Lys His Pro Arg Ser Leu Leu 225 230 235 240 Ile Leu Asp Asp Val Trp Asp Ser Trp Val Leu Lys Ala Phe Asp Ser 245 250 255 Gln Cys Gln Ile Leu Leu Thr Thr Arg Asp Lys Ser Val Thr Asp Ser 260 265 270 Val Met Gly Pro Lys Tyr Val Val Pro Val Glu Ser Ser Leu Gly Lys 275 280 285 Glu Lys Gly Leu Glu Ile Leu Ser Leu Phe Val Asn Met Lys Lys Ala 290 295 300 Asp Leu Pro Glu Gln Ala His Ser Ile Ile Lys Glu Cys Lys Gly Ser 305 310 315 320 Pro Leu Val Val Ser Leu Ile Gly Ala Leu Leu Arg Asp Phe Pro Asn 325 330 335 Arg Trp Glu Tyr Tyr Leu Lys Gln Leu Gln Asn Lys Gln Phe Lys Arg 340 345 350 Ile Arg Lys Ser Ser Ser Tyr Asp Tyr Glu Ala Leu Asp Glu Ala Met 355 360 365 Ser Ile Ser Val Glu Met Leu Arg Glu Asp Ile Lys Asp Tyr Tyr Thr 370 375 380 Asp Leu Ser Ile Leu Gln Lys Asp Val Lys Val Pro Thr Lys Val Leu 385 390 395 400 Cys Ile Leu Trp Asp Met Glu Thr Glu Glu Val Glu Asp Ile Leu Gln 405 410 415 Glu Phe Val Asn Lys Ser Leu Leu Phe Cys Asp Arg Asn Gly Lys Ser 420 425 430 Phe Arg Tyr Tyr Leu His Asp Leu Gln Val Asp Phe Leu Thr Glu Lys 435 440 445 Asn Cys Ser Gln Leu Gln Asp Leu His Lys Lys Ile Ile Thr Gln Phe 450 455 460 Gln Arg Tyr His Gln Pro His Thr Leu Ser Pro Asp Gln Glu Asp Cys 465 470 475 480 Met Tyr Trp Tyr Asn Phe Leu Ala Tyr His Met Ala Ser Ala Lys Met 485 490 495 His Lys Glu Leu Cys Ala Leu Met Phe Ser Leu Asp Trp Ile Lys Ala 500 505 510 Lys Thr Glu Leu Val Gly Pro Ala His Leu Ile His Glu Phe Val Glu 515 520 525 Tyr Arg His Ile Leu Asp Glu Lys Asp Cys Ala Val Ser Glu Asn Phe 530 535 540 Gln Glu Phe Leu Ser Leu Asn Gly His Leu Leu Gly Arg Gln Pro Phe 545 550 555 560 Pro Asn Ile Val Gln Leu Gly Leu Cys Glu Pro Glu Thr Ser Glu Val 565 570 575 Tyr Gln Gln Ala Lys Leu Gln Ala Lys Gln Glu Val Asp Asn Gly Met 580 585 590 Leu Tyr Leu Glu Trp Ile Asn Lys Lys Asn Ile Thr Asn Leu Ser Arg 595 600 605 Leu Val Val Arg Pro His Thr Asp Ala Val Tyr His Ala Cys Phe Ser 610 615 620 Glu Asp Gly Gln Arg Ile Ala Ser Cys Gly Ala Asp Lys Thr Leu Gln 625 630 635 640 Val Phe Lys Ala Glu Thr Gly Glu Lys Leu Leu Glu Ile Lys Ala His 645 650 655 Glu Asp Glu Val Leu Cys Cys Ala Phe Ser Thr Asp Asp Arg Phe Ile 660 665 670 Ala Thr Cys Ser Val Asp Lys Lys Val Lys Ile Trp Asn Ser Met Thr 675 680 685 Gly Glu Leu Val His Thr Tyr Asp Glu His Ser Glu Gln Val Asn Cys 690 695 700 Cys His Phe Thr Asn Ser Ser His His Leu Leu Leu Ala Thr Gly Ser 705 710 715 720 Ser Asp Cys Phe Leu Lys Leu Trp Asp Leu Asn Gln Lys Glu Cys Arg 725 730 735 Asn Thr Met Phe Gly His Thr Asn Ser Val Asn His Cys Arg Phe Ser 740 745 750 Pro Asp Asp Lys Leu Leu Ala Ser Cys Ser Ala Asp Gly Thr Leu Lys 755 760 765 Leu Trp Asp Ala Thr Ser Ala Asn Glu Arg Lys Ser Ile Asn Val Lys 770 775 780 Gln Phe Phe Leu Asn Leu Glu Asp Pro Gln Glu Asp Met Glu Val Ile 785 790 795 800 Val Lys Cys Cys Ser Trp Ser Ala Asp Gly Ala Arg Ile Met Val Ala 805 810 815 Ala Lys Asn Lys Ile Phe Leu Phe Asp Ile His Thr Ser Gly Leu Leu 820 825 830 Gly Glu Ile His Thr Gly His His Ser Thr Ile Gln Tyr Cys Asp Phe 835 840 845 Ser Pro Gln Asn His Leu Ala Val Val Ala Leu Ser Gln Tyr Cys Val 850 855 860 Glu Leu Trp Asn Thr Asp Ser Arg Ser Lys Val Ala Asp Cys Arg Gly 865 870 875 880 His Leu Ser Trp Val His Gly Val Met Phe Ser Pro Asp Gly Ser Ser 885 890 895 Phe Leu Thr Ser Ser Asp Asp Gln Thr Ile Arg Leu Trp Glu Thr Lys 900 905 910 Lys Val Cys Lys Asn Ser Ala Val Met Leu Lys Gln Glu Val Asp Val 915 920 925 Val Phe Gln Glu Asn Glu Val Met Val Leu Ala Val Asp His Ile Arg 930 935 940 Arg Leu Gln Leu Ile Asn Gly Arg Thr Gly Gln Ile Asp Tyr Leu Thr 945 950 955 960 Glu Ala Gln Val Ser Cys Cys Cys Leu Ser Pro His Leu Gln Tyr Ile 965 970 975 Ala Phe Gly Asp Glu Asn Gly Ala Ile Glu Ile Leu Glu Leu Val Asn 980 985 990 Asn Arg Ile Phe Gln Ser Arg Phe Gln His Lys Lys Thr Val Trp His 995 1000 1005 Ile Gln Phe Thr Ala Asp Glu Lys Thr Leu Ile Ser Ser Ser Asp Asp 1010 1015 1020 Ala Glu Ile Gln Val Trp Asn Trp Gln Leu Asp Lys Cys Ile Phe Leu 1025 1030 1035 1040 Arg Gly His Gln Glu Thr Val Lys Asp Phe Arg Leu Leu Lys Asn Ser 1045 1050 1055 Arg Leu Leu Ser Trp Ser Phe Asp Gly Thr Val Lys Val Trp Asn Ile 1060 1065 1070 Ile Thr Gly Asn Lys Glu Lys Asp Phe Val Cys His Gln Gly Thr Val 1075 1080 1085 Leu Ser Cys Asp Ile Ser His Asp Ala Thr Lys Phe Ser Ser Thr Ser 1090 1095 1100 Ala Asp Lys Thr Ala Lys Ile Trp Ser Phe Asp Leu Leu Leu Pro Leu 1105 1110 1115 1120 His Glu Leu Arg Gly His Asn Gly Cys Val Arg Cys Ser Ala Phe Ser 1125 1130 1135 Val Asp Ser Thr Leu Leu Ala Thr Gly Asp Asp Asn Gly Glu Ile Arg 1140 1145 1150 Ile Trp Asn Val Ser Asn Gly Glu Leu Leu His Leu Cys Ala Pro Leu 1155 1160 1165 Ser Glu Glu Gly Ala Ala Thr His Gly Gly Trp Val Thr Asp Leu Cys 1170 1175 1180 Phe Ser Pro Asp Gly Lys Met Leu Ile Ser Ala Gly Gly Tyr Ile Lys 1185 1190 1195 1200 Trp Trp Asn Val Val Thr Gly Glu Ser Ser Gln Thr Phe Tyr Thr Asn 1205 1210 1215 Gly Thr Asn Leu Lys Lys Ile His Val Ser Pro Asp Phe Lys Thr Tyr 1220 1225 1230 Val Thr Val Asp Asn Leu Gly Ile Leu Tyr Ile Leu Gln Thr Leu Glu 1235 1240 1245 <210> SEQ ID NO 52 <211> LENGTH: 1205 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 52 Met Asp Ala Lys Ala Arg Asn Cys Leu Leu Gln His Arg Glu Ala Leu 1 5 10 15 Glu Lys Asp Ile Lys Thr Ser Tyr Ile Met Asp His Met Ile Ser Asp 20 25 30 Gly Phe Leu Thr Ile Ser Glu Glu Glu Lys Val Arg Asn Glu Pro Thr 35 40 45 Gln Gln Gln Arg Ala Ala Met Leu Ile Lys Met Ile Leu Lys Lys Asp 50 55 60 Asn Asp Ser Tyr Val Ser Phe Tyr Asn Ala Leu Leu His Glu Gly Tyr 65 70 75 80 Lys Asp Leu Ala Ala Leu Leu His Asp Gly Ile Pro Val Val Ser Ser 85 90 95 Ser Ser Gly Lys Asp Ser Val Ser Gly Ile Thr Ser Tyr Val Arg Thr 100 105 110 Val Leu Cys Glu Gly Gly Val Pro Gln Arg Pro Val Val Phe Val Thr 115 120 125 Arg Lys Lys Leu Val Asn Ala Ile Gln Gln Lys Leu Ser Lys Leu Lys 130 135 140 Gly Glu Pro Gly Trp Val Thr Ile His Gly Met Ala Gly Cys Gly Lys 145 150 155 160 Ser Val Leu Ala Ala Glu Ala Val Arg Asp His Ser Leu Leu Glu Gly 165 170 175 Cys Phe Pro Gly Gly Val His Trp Val Ser Val Gly Lys Gln Asp Lys 180 185 190 Ser Gly Leu Leu Met Lys Leu Gln Asn Leu Cys Thr Arg Leu Asp Gln 195 200 205 Asp Glu Ser Phe Ser Gln Arg Leu Pro Leu Asn Ile Glu Glu Ala Lys 210 215 220 Asp Arg Leu Arg Ile Leu Met Leu Arg Lys His Pro Arg Ser Leu Leu 225 230 235 240 Ile Leu Asp Asp Val Trp Asp Ser Trp Val Leu Lys Ala Phe Asp Ser 245 250 255 Gln Cys Gln Ile Leu Leu Thr Thr Arg Asp Lys Ser Val Thr Asp Ser 260 265 270 Val Met Gly Pro Lys Tyr Val Val Pro Val Glu Ser Ser Leu Gly Lys 275 280 285 Glu Lys Gly Leu Glu Ile Leu Ser Leu Phe Val Asn Met Lys Lys Ala 290 295 300 Asp Leu Pro Glu Gln Ala His Ser Ile Ile Lys Glu Cys Lys Gly Ser 305 310 315 320 Pro Leu Val Val Ser Leu Ile Gly Ala Leu Leu Arg Asp Phe Pro Asn 325 330 335 Arg Trp Glu Tyr Tyr Leu Lys Gln Leu Gln Asn Lys Gln Phe Lys Arg 340 345 350 Ile Arg Lys Ser Ser Ser Tyr Asp Tyr Glu Ala Leu Asp Glu Ala Met 355 360 365 Ser Ile Ser Val Glu Met Leu Arg Glu Asp Ile Lys Asp Tyr Tyr Thr 370 375 380 Asp Leu Ser Ile Leu Gln Lys Asp Val Lys Val Pro Thr Lys Val Leu 385 390 395 400 Cys Ile Leu Trp Asp Met Glu Thr Glu Glu Val Glu Asp Ile Leu Gln 405 410 415 Glu Phe Val Asn Lys Ser Leu Leu Phe Cys Asp Arg Asn Gly Lys Ser 420 425 430 Phe Arg Tyr Tyr Leu His Asp Leu Gln Val Asp Phe Leu Thr Glu Lys 435 440 445 Asn Cys Ser Gln Leu Gln Asp Leu His Lys Lys Ile Ile Thr Gln Phe 450 455 460 Gln Arg Tyr His Gln Pro His Thr Leu Ser Pro Asp Gln Glu Asp Cys 465 470 475 480 Met Tyr Trp Tyr Asn Phe Leu Ala Tyr His Met Ala Ser Ala Lys Met 485 490 495 His Lys Glu Leu Cys Ala Leu Met Phe Ser Leu Asp Trp Ile Lys Ala 500 505 510 Lys Thr Glu Leu Val Gly Pro Ala His Leu Ile His Glu Phe Val Glu 515 520 525 Tyr Arg His Ile Leu Asp Glu Lys Asp Cys Ala Val Ser Glu Asn Phe 530 535 540 Gln Glu Phe Leu Ser Leu Asn Gly His Leu Leu Gly Arg Gln Pro Phe 545 550 555 560 Pro Asn Ile Val Gln Leu Gly Leu Cys Glu Pro Glu Thr Ser Glu Val 565 570 575 Tyr Gln Gln Ala Lys Leu Gln Ala Lys Gln Glu Val Asp Asn Gly Met 580 585 590 Leu Tyr Leu Glu Trp Ile Asn Lys Lys Asn Ile Thr Asn Leu Ser Arg 595 600 605 Leu Val Val Arg Pro His Thr Asp Ala Val Tyr His Ala Cys Phe Ser 610 615 620 Glu Asp Gly Gln Arg Ile Ala Ser Cys Gly Ala Asp Lys Thr Leu Gln 625 630 635 640 Val Phe Lys Ala Glu Thr Gly Glu Lys Leu Leu Glu Ile Lys Ala His 645 650 655 Glu Asp Glu Val Leu Cys Cys Ala Phe Ser Thr Asp Asp Arg Phe Ile 660 665 670 Ala Thr Cys Ser Val Asp Lys Lys Val Lys Ile Trp Asn Ser Met Thr 675 680 685 Gly Glu Leu Val His Thr Tyr Asp Glu His Ser Glu Gln Val Asn Cys 690 695 700 Cys His Phe Thr Asn Ser Ser His His Leu Leu Leu Ala Thr Gly Ser 705 710 715 720 Ser Asp Cys Phe Leu Lys Leu Trp Asp Leu Asn Gln Lys Glu Cys Arg 725 730 735 Asn Thr Met Phe Gly His Thr Asn Ser Val Asn His Cys Arg Phe Ser 740 745 750 Pro Asp Asp Lys Leu Leu Ala Ser Cys Ser Ala Asp Gly Thr Leu Lys 755 760 765 Leu Trp Asp Ala Thr Ser Ala Asn Glu Arg Lys Ser Ile Asn Val Lys 770 775 780 Gln Phe Phe Leu Asn Leu Glu Asp Pro Gln Glu Asp Met Glu Val Ile 785 790 795 800 Val Lys Cys Cys Ser Trp Ser Ala Asp Gly Ala Arg Ile Met Val Ala 805 810 815 Ala Lys Asn Lys Ile Phe Leu Trp Asn Thr Asp Ser Arg Ser Lys Val 820 825 830 Ala Asp Cys Arg Gly His Leu Ser Trp Val His Gly Val Met Phe Ser 835 840 845 Pro Asp Gly Ser Ser Phe Leu Thr Ser Ser Asp Asp Gln Thr Ile Arg 850 855 860 Leu Trp Glu Thr Lys Lys Val Cys Lys Asn Ser Ala Val Met Leu Lys 865 870 875 880 Gln Glu Val Asp Val Val Phe Gln Glu Asn Glu Val Met Val Leu Ala 885 890 895 Val Asp His Ile Arg Arg Leu Gln Leu Ile Asn Gly Arg Thr Gly Gln 900 905 910 Ile Asp Tyr Leu Thr Glu Ala Gln Val Ser Cys Cys Cys Leu Ser Pro 915 920 925 His Leu Gln Tyr Ile Ala Phe Gly Asp Glu Asn Gly Ala Ile Glu Ile 930 935 940 Leu Glu Leu Val Asn Asn Arg Ile Phe Gln Ser Arg Phe Gln His Lys 945 950 955 960 Lys Thr Val Trp His Ile Gln Phe Thr Ala Asp Glu Lys Thr Leu Ile 965 970 975 Ser Ser Ser Asp Asp Ala Glu Ile Gln Val Trp Asn Trp Gln Leu Asp 980 985 990 Lys Cys Ile Phe Leu Arg Gly His Gln Glu Thr Val Lys Asp Phe Arg 995 1000 1005 Leu Leu Lys Asn Ser Arg Leu Leu Ser Trp Ser Phe Asp Gly Thr Val 1010 1015 1020 Lys Val Trp Asn Ile Ile Thr Gly Asn Lys Glu Lys Asp Phe Val Cys 1025 1030 1035 1040 His Gln Gly Thr Val Leu Ser Cys Asp Ile Ser His Asp Ala Thr Lys 1045 1050 1055 Phe Ser Ser Thr Ser Ala Asp Lys Thr Ala Lys Ile Trp Ser Phe Asp 1060 1065 1070 Leu Leu Leu Pro Leu His Glu Leu Arg Gly His Asn Gly Cys Val Arg 1075 1080 1085 Cys Ser Ala Phe Ser Val Asp Ser Thr Leu Leu Ala Thr Gly Asp Asp 1090 1095 1100 Asn Gly Glu Ile Arg Ile Trp Asn Val Ser Asn Gly Glu Leu Leu His 1105 1110 1115 1120 Leu Cys Ala Pro Leu Ser Glu Glu Gly Ala Ala Thr His Gly Gly Trp 1125 1130 1135 Val Thr Asp Leu Cys Phe Ser Pro Asp Gly Lys Met Leu Ile Ser Ala 1140 1145 1150 Gly Gly Tyr Ile Lys Trp Trp Asn Val Val Thr Gly Glu Ser Ser Gln 1155 1160 1165 Thr Phe Tyr Thr Asn Gly Thr Asn Leu Lys Lys Ile His Val Ser Pro 1170 1175 1180 Asp Phe Lys Thr Tyr Val Thr Val Asp Asn Leu Gly Ile Leu Tyr Ile 1185 1190 1195 1200 Leu Gln Thr Leu Glu 1205 <210> SEQ ID NO 53 <211> LENGTH: 338 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 53 Met Asp Ala Lys Ala Arg Asn Cys Leu Leu Gln His Arg Glu Ala Leu 1 5 10 15 Glu Lys Asp Ile Lys Thr Ser Tyr Ile Met Asp His Met Ile Ser Asp 20 25 30 Gly Phe Leu Thr Ile Ser Glu Glu Glu Lys Val Arg Asn Glu Pro Thr 35 40 45 Gln Gln Gln Arg Ala Ala Met Leu Ile Lys Met Ile Leu Lys Lys Asp 50 55 60 Asn Asp Ser Tyr Val Ser Phe Tyr Asn Ala Leu Leu His Glu Gly Tyr 65 70 75 80 Lys Asp Leu Ala Ala Leu Leu His Asp Gly Ile Pro Val Val Ser Ser 85 90 95 Ser Ser Gly Lys Asp Ser Val Ser Gly Ile Thr Ser Tyr Val Arg Thr 100 105 110 Val Leu Cys Glu Gly Gly Val Pro Gln Arg Pro Val Val Phe Val Thr 115 120 125 Arg Lys Lys Leu Val Asn Ala Ile Gln Gln Lys Leu Ser Lys Leu Lys 130 135 140 Gly Glu Pro Gly Trp Val Thr Ile His Gly Met Ala Gly Cys Gly Lys 145 150 155 160 Ser Val Leu Ala Ala Glu Ala Val Arg Asp His Ser Leu Leu Glu Gly 165 170 175 Cys Phe Pro Gly Gly Val His Trp Val Ser Val Gly Lys Gln Asp Lys 180 185 190 Ser Gly Leu Leu Met Lys Leu Gln Asn Leu Cys Thr Arg Leu Asp Gln 195 200 205 Asp Glu Ser Phe Ser Gln Arg Leu Pro Leu Asn Ile Glu Glu Ala Lys 210 215 220 Asp Arg Leu Arg Ile Leu Met Leu Arg Lys His Pro Arg Ser Leu Leu 225 230 235 240 Ile Leu Asp Asp Val Trp Asp Ser Trp Val Leu Lys Ala Phe Asp Ser 245 250 255 Gln Cys Gln Ile Leu Leu Thr Thr Arg Asp Lys Ser Val Thr Asp Ser 260 265 270 Val Met Gly Pro Lys Tyr Val Val Pro Val Glu Ser Ser Leu Gly Lys 275 280 285 Glu Lys Gly Leu Glu Ile Leu Ser Leu Phe Val Asn Met Lys Lys Ala 290 295 300 Asp Leu Pro Glu Gln Ala His Ser Ile Ile Lys Glu Cys Lys Val Val 305 310 315 320 Glu Arg Cys His Trp Gly Ile Leu Thr Asp Leu Leu His Lys Trp Asn 325 330 335 Gln Ser <210> SEQ ID NO 54 <211> LENGTH: 281 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 54 Met Ala Met Met Glu Val Gln Gly Gly Pro Ser Leu Gly Gln Thr Cys 1 5 10 15 Val Leu Ile Val Ile Phe Thr Val Leu Leu Gln Ser Leu Cys Val Ala 20 25 30 Val Thr Tyr Val Tyr Phe Thr Asn Glu Leu Lys Gln Met Gln Asp Lys 35 40 45 Tyr Ser Lys Ser Gly Ile Ala Cys Phe Leu Lys Glu Asp Asp Ser Tyr 50 55 60 Trp Asp Pro Asn Asp Glu Glu Ser Met Asn Ser Pro Cys Trp Gln Val 65 70 75 80 Lys Trp Gln Leu Arg Gln Leu Val Arg Lys Met Ile Leu Arg Thr Ser 85 90 95 Glu Glu Thr Ile Ser Thr Val Gln Glu Lys Gln Gln Asn Ile Ser Pro 100 105 110 Leu Val Arg Glu Arg Gly Pro Gln Arg Val Ala Ala His Ile Thr Gly 115 120 125 Thr Arg Gly Arg Ser Asn Thr Leu Ser Ser Pro Asn Ser Lys Asn Glu 130 135 140 Lys Ala Leu Gly Arg Lys Ile Asn Ser Trp Glu Ser Ser Arg Ser Gly 145 150 155 160 His Ser Phe Leu Ser Asn Leu His Leu Arg Asn Gly Glu Leu Val Ile 165 170 175 His Glu Lys Gly Phe Tyr Tyr Ile Tyr Ser Gln Thr Tyr Phe Arg Phe 180 185 190 Gln Glu Glu Ile Lys Glu Asn Thr Lys Asn Asp Lys Gln Met Val Gln 195 200 205 Tyr Ile Tyr Lys Tyr Thr Ser Tyr Pro Asp Pro Ile Leu Leu Met Lys 210 215 220 Ser Ala Arg Asn Ser Cys Trp Ser Lys Asp Ala Glu Tyr Gly Leu Tyr 225 230 235 240 Ser Ile Tyr Gln Gly Gly Ile Phe Glu Leu Lys Glu Asn Asp Arg Ile 245 250 255 Phe Val Ser Val Thr Asn Glu His Leu Ile Asp Met Asp His Glu Ala 260 265 270 Ser Phe Phe Gly Ala Phe Leu Val Gly 275 280 <210> SEQ ID NO 55 <211> LENGTH: 277 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 55 Met Glu Asn Thr Glu Asn Ser Val Asp Ser Lys Ser Ile Lys Asn Leu 1 5 10 15 Glu Pro Lys Ile Ile His Gly Ser Glu Ser Met Asp Ser Gly Ile Ser 20 25 30 Leu Asp Asn Ser Tyr Lys Met Asp Tyr Pro Glu Met Gly Leu Cys Ile 35 40 45 Ile Ile Asn Asn Lys Asn Phe His Lys Ser Thr Gly Met Thr Ser Arg 50 55 60 Ser Gly Thr Asp Val Asp Ala Ala Asn Leu Arg Glu Thr Phe Arg Asn 65 70 75 80 Leu Lys Tyr Glu Val Arg Asn Lys Asn Asp Leu Thr Arg Glu Glu Ile 85 90 95 Val Glu Leu Met Arg Asp Val Ser Lys Glu Asp His Ser Lys Arg Ser 100 105 110 Ser Phe Val Cys Val Leu Leu Ser His Gly Glu Glu Gly Ile Ile Phe 115 120 125 Gly Thr Asn Gly Pro Val Asp Leu Lys Lys Ile Thr Asn Phe Phe Arg 130 135 140 Gly Asp Arg Cys Arg Ser Leu Thr Gly Lys Pro Lys Leu Phe Ile Ile 145 150 155 160 Gln Ala Cys Arg Gly Thr Glu Leu Asp Cys Gly Ile Glu Thr Asp Ser 165 170 175 Gly Val Asp Asp Asp Met Ala Cys His Lys Ile Pro Val Glu Ala Asp 180 185 190 Phe Leu Tyr Ala Tyr Ser Thr Ala Pro Gly Tyr Tyr Ser Trp Arg Asn 195 200 205 Ser Lys Asp Gly Ser Trp Phe Ile Gln Ser Leu Cys Ala Met Leu Lys 210 215 220 Gln Tyr Ala Asp Lys Leu Glu Phe Met His Ile Leu Thr Arg Val Asn 225 230 235 240 Arg Lys Val Ala Thr Glu Phe Glu Ser Phe Ser Phe Asp Ala Thr Phe 245 250 255 His Ala Lys Lys Gln Ile Pro Cys Ile Val Ser Met Leu Thr Lys Glu 260 265 270 Leu Tyr Phe Tyr His 275 <210> SEQ ID NO 56 <211> LENGTH: 192 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 56 Met Asp Gly Ser Gly Glu Gln Pro Arg Gly Gly Gly Pro Thr Ser Ser 1 5 10 15 Glu Gln Ile Met Lys Thr Gly Ala Leu Leu Leu Gln Gly Phe Ile Gln 20 25 30 Asp Arg Ala Gly Arg Met Gly Gly Glu Ala Pro Glu Leu Ala Leu Asp 35 40 45 Pro Val Pro Gln Asp Ala Ser Thr Lys Lys Leu Ser Glu Cys Leu Lys 50 55 60 Arg Ile Gly Asp Glu Leu Asp Ser Asn Met Glu Leu Gln Arg Met Ile 65 70 75 80 Ala Ala Val Asp Thr Asp Ser Pro Arg Glu Val Phe Phe Arg Val Ala 85 90 95 Ala Asp Met Phe Ser Asp Gly Asn Phe Asn Trp Gly Arg Val Val Ala 100 105 110 Leu Phe Tyr Phe Ala Ser Lys Leu Val Leu Lys Ala Leu Cys Thr Lys 115 120 125 Val Pro Glu Leu Ile Arg Thr Ile Met Gly Trp Thr Leu Asp Phe Leu 130 135 140 Arg Glu Arg Leu Leu Gly Trp Ile Gln Asp Gln Gly Gly Trp Asp Gly 145 150 155 160 Leu Leu Ser Tyr Phe Gly Thr Pro Thr Trp Gln Thr Val Thr Ile Phe 165 170 175 Val Ala Gly Val Leu Thr Ala Ser Leu Thr Ile Trp Lys Lys Met Gly 180 185 190 <210> SEQ ID NO 57 <211> LENGTH: 168 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 57 Met Phe Gln Ile Pro Glu Phe Glu Pro Ser Glu Gln Glu Asp Ser Ser 1 5 10 15 Ser Ala Glu Arg Gly Leu Gly Pro Ser Pro Ala Gly Asp Gly Pro Ser 20 25 30 Gly Ser Gly Lys His His Arg Gln Ala Pro Gly Leu Leu Trp Asp Ala 35 40 45 Ser His Gln Gln Glu Gln Pro Thr Ser Ser Ser His His Gly Gly Ala 50 55 60 Gly Ala Val Glu Ile Arg Ser Arg His Ser Ser Tyr Pro Ala Gly Thr 65 70 75 80 Glu Asp Asp Glu Gly Met Gly Glu Glu Pro Ser Pro Phe Arg Gly Arg 85 90 95 Ser Arg Ser Ala Pro Pro Asn Leu Trp Ala Ala Gln Arg Tyr Gly Arg 100 105 110 Glu Leu Arg Arg Met Ser Asp Glu Phe Val Asp Ser Phe Lys Lys Gly 115 120 125 Leu Pro Arg Pro Lys Ser Ala Gly Thr Ala Thr Gln Met Arg Gln Ser 130 135 140 Ser Ser Trp Thr Arg Val Phe Gln Ser Trp Trp Asp Arg Asn Leu Gly 145 150 155 160 Arg Gly Ser Ser Ala Pro Ser Gln 165 <210> SEQ ID NO 58 <211> LENGTH: 208 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 58 Met Asp Pro Phe Leu Val Leu Leu His Ser Val Ser Ser Ser Leu Ser 1 5 10 15 Ser Ser Glu Leu Thr Glu Leu Lys Phe Leu Cys Leu Gly Arg Val Gly 20 25 30 Lys Arg Lys Leu Glu Arg Val Gln Ser Gly Leu Asp Leu Phe Ser Met 35 40 45 Leu Leu Glu Gln Asn Asp Leu Glu Pro Gly His Thr Glu Leu Leu Arg 50 55 60 Glu Leu Leu Ala Ser Leu Arg Arg His Asp Leu Leu Arg Arg Val Asp 65 70 75 80 Asp Phe Glu Ala Gly Ala Ala Ala Gly Ala Ala Pro Gly Glu Glu Asp 85 90 95 Leu Cys Ala Ala Phe Asn Val Ile Cys Asp Asn Val Gly Lys Asp Trp 100 105 110 Arg Arg Leu Ala Arg Gln Leu Lys Val Ser Asp Thr Lys Ile Asp Ser 115 120 125 Ile Glu Asp Arg Tyr Pro Arg Asn Leu Thr Glu Arg Val Arg Glu Ser 130 135 140 Leu Arg Ile Trp Lys Asn Thr Glu Lys Glu Asn Ala Thr Val Ala His 145 150 155 160 Leu Val Gly Ala Leu Arg Ser Cys Gln Met Asn Leu Val Ala Asp Leu 165 170 175 Val Gln Glu Val Gln Gln Ala Arg Asp Leu Gln Asn Arg Ser Gly Ala 180 185 190 Met Ser Pro Met Ser Trp Asn Ser Asp Ala Ser Thr Ser Glu Ala Ser 195 200 205 <210> SEQ ID NO 59 <211> LENGTH: 384 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 59 Met Ser Arg Ser Lys Arg Asp Asn Asn Phe Tyr Ser Val Glu Ile Gly 1 5 10 15 Asp Ser Thr Phe Thr Val Leu Lys Arg Tyr Gln Asn Leu Lys Pro Ile 20 25 30 Gly Ser Gly Ala Gln Gly Ile Val Cys Ala Ala Tyr Asp Ala Ile Leu 35 40 45 Glu Arg Asn Val Ala Ile Lys Lys Leu Ser Arg Pro Phe Gln Asn Gln 50 55 60 Thr His Ala Lys Arg Ala Tyr Arg Glu Leu Val Leu Met Lys Cys Val 65 70 75 80 Asn His Lys Asn Ile Ile Gly Leu Leu Asn Val Phe Thr Pro Gln Lys 85 90 95 Ser Leu Glu Glu Phe Gln Asp Val Tyr Ile Val Met Glu Leu Met Asp 100 105 110 Ala Asn Leu Cys Gln Val Ile Gln Met Glu Leu Asp His Glu Arg Met 115 120 125 Ser Tyr Leu Leu Tyr Gln Met Leu Cys Gly Ile Lys His Leu His Ser 130 135 140 Ala Gly Ile Ile His Arg Asp Leu Lys Pro Ser Asn Ile Val Val Lys 145 150 155 160 Ser Asp Cys Thr Leu Lys Ile Leu Asp Phe Gly Leu Ala Arg Thr Ala 165 170 175 Gly Thr Ser Phe Met Met Thr Pro Tyr Val Val Thr Arg Tyr Tyr Arg 180 185 190 Ala Pro Glu Val Ile Leu Gly Met Gly Tyr Lys Glu Asn Val Asp Leu 195 200 205 Trp Ser Val Gly Cys Ile Met Gly Glu Met Val Cys His Lys Ile Leu 210 215 220 Phe Pro Gly Arg Asp Tyr Ile Asp Gln Trp Asn Lys Val Ile Glu Gln 225 230 235 240 Leu Gly Thr Pro Cys Pro Glu Phe Met Lys Lys Leu Gln Pro Thr Val 245 250 255 Arg Thr Tyr Val Glu Asn Arg Pro Lys Tyr Ala Gly Tyr Ser Phe Glu 260 265 270 Lys Leu Phe Pro Asp Val Leu Phe Pro Ala Asp Ser Glu His Asn Lys 275 280 285 Leu Lys Ala Ser Gln Ala Arg Asp Leu Leu Ser Lys Met Leu Val Ile 290 295 300 Asp Ala Ser Lys Arg Ile Ser Val Asp Glu Ala Leu Gln His Pro Tyr 305 310 315 320 Ile Asn Val Trp Tyr Asp Pro Ser Glu Ala Glu Ala Pro Pro Pro Lys 325 330 335 Ile Pro Asp Lys Gln Leu Asp Glu Arg Glu His Thr Ile Glu Glu Trp 340 345 350 Lys Glu Leu Ile Tyr Lys Glu Val Met Asp Leu Glu Glu Arg Thr Lys 355 360 365 Asn Gly Val Ile Arg Gly Gln Pro Ser Pro Leu Ala Gln Val Gln Gln 370 375 380 <210> SEQ ID NO 60 <211> LENGTH: 427 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 60 Met Ser Arg Ser Lys Arg Asp Asn Asn Phe Tyr Ser Val Glu Ile Gly 1 5 10 15 Asp Ser Thr Phe Thr Val Leu Lys Arg Tyr Gln Asn Leu Lys Pro Ile 20 25 30 Gly Ser Gly Ala Gln Gly Ile Val Cys Ala Ala Tyr Asp Ala Ile Leu 35 40 45 Glu Arg Asn Val Ala Ile Lys Lys Leu Ser Arg Pro Phe Gln Asn Gln 50 55 60 Thr His Ala Lys Arg Ala Tyr Arg Glu Leu Val Leu Met Lys Cys Val 65 70 75 80 Asn His Lys Asn Ile Ile Gly Leu Leu Asn Val Phe Thr Pro Gln Lys 85 90 95 Ser Leu Glu Glu Phe Gln Asp Val Tyr Ile Val Met Glu Leu Met Asp 100 105 110 Ala Asn Leu Cys Gln Val Ile Gln Met Glu Leu Asp His Glu Arg Met 115 120 125 Ser Tyr Leu Leu Tyr Gln Met Leu Cys Gly Ile Lys His Leu His Ser 130 135 140 Ala Gly Ile Ile His Arg Asp Leu Lys Pro Ser Asn Ile Val Val Lys 145 150 155 160 Ser Asp Cys Thr Leu Lys Ile Leu Asp Phe Gly Leu Ala Arg Thr Ala 165 170 175 Gly Thr Ser Phe Met Met Thr Pro Tyr Val Val Thr Arg Tyr Tyr Arg 180 185 190 Ala Pro Glu Val Ile Leu Gly Met Gly Tyr Lys Glu Asn Val Asp Leu 195 200 205 Trp Ser Val Gly Cys Ile Met Gly Glu Met Val Cys His Lys Ile Leu 210 215 220 Phe Pro Gly Arg Asp Tyr Ile Asp Gln Trp Asn Lys Val Ile Glu Gln 225 230 235 240 Leu Gly Thr Pro Cys Pro Glu Phe Met Lys Lys Leu Gln Pro Thr Val 245 250 255 Arg Thr Tyr Val Glu Asn Arg Pro Lys Tyr Ala Gly Tyr Ser Phe Glu 260 265 270 Lys Leu Phe Pro Asp Val Leu Phe Pro Ala Asp Ser Glu His Asn Lys 275 280 285 Leu Lys Ala Ser Gln Ala Arg Asp Leu Leu Ser Lys Met Leu Val Ile 290 295 300 Asp Ala Ser Lys Arg Ile Ser Val Asp Glu Ala Leu Gln His Pro Tyr 305 310 315 320 Ile Asn Val Trp Tyr Asp Pro Ser Glu Ala Glu Ala Pro Pro Pro Lys 325 330 335 Ile Pro Asp Lys Gln Leu Asp Glu Arg Glu His Thr Ile Glu Glu Trp 340 345 350 Lys Glu Leu Ile Tyr Lys Glu Val Met Asp Leu Glu Glu Arg Thr Lys 355 360 365 Asn Gly Val Ile Arg Gly Gln Pro Ser Pro Leu Gly Ala Ala Val Ile 370 375 380 Asn Gly Ser Gln His Pro Ser Ser Ser Ser Ser Val Asn Asp Val Ser 385 390 395 400 Ser Met Ser Thr Asp Pro Thr Leu Ala Ser Asp Thr Asp Ser Ser Leu 405 410 415 Glu Ala Ala Ala Gly Pro Leu Gly Cys Cys Arg 420 425 <210> SEQ ID NO 61 <211> LENGTH: 384 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 61 Met Ser Arg Ser Lys Arg Asp Asn Asn Phe Tyr Ser Val Glu Ile Gly 1 5 10 15 Asp Ser Thr Phe Thr Val Leu Lys Arg Tyr Gln Asn Leu Lys Pro Ile 20 25 30 Gly Ser Gly Ala Gln Gly Ile Val Cys Ala Ala Tyr Asp Ala Ile Leu 35 40 45 Glu Arg Asn Val Ala Ile Lys Lys Leu Ser Arg Pro Phe Gln Asn Gln 50 55 60 Thr His Ala Lys Arg Ala Tyr Arg Glu Leu Val Leu Met Lys Cys Val 65 70 75 80 Asn His Lys Asn Ile Ile Gly Leu Leu Asn Val Phe Thr Pro Gln Lys 85 90 95 Ser Leu Glu Glu Phe Gln Asp Val Tyr Ile Val Met Glu Leu Met Asp 100 105 110 Ala Asn Leu Cys Gln Val Ile Gln Met Glu Leu Asp His Glu Arg Met 115 120 125 Ser Tyr Leu Leu Tyr Gln Met Leu Cys Gly Ile Lys His Leu His Ser 130 135 140 Ala Gly Ile Ile His Arg Asp Leu Lys Pro Ser Asn Ile Val Val Lys 145 150 155 160 Ser Asp Cys Thr Leu Lys Ile Leu Asp Phe Gly Leu Ala Arg Thr Ala 165 170 175 Gly Thr Ser Phe Met Met Thr Pro Tyr Val Val Thr Arg Tyr Tyr Arg 180 185 190 Ala Pro Glu Val Ile Leu Gly Met Gly Tyr Lys Glu Asn Val Asp Ile 195 200 205 Trp Ser Val Gly Cys Ile Met Gly Glu Met Ile Lys Gly Gly Val Leu 210 215 220 Phe Pro Gly Thr Asp His Ile Asp Gln Trp Asn Lys Val Ile Glu Gln 225 230 235 240 Leu Gly Thr Pro Cys Pro Glu Phe Met Lys Lys Leu Gln Pro Thr Val 245 250 255 Arg Thr Tyr Val Glu Asn Arg Pro Lys Tyr Ala Gly Tyr Ser Phe Glu 260 265 270 Lys Leu Phe Pro Asp Val Leu Phe Pro Ala Asp Ser Glu His Asn Lys 275 280 285 Leu Lys Ala Ser Gln Ala Arg Asp Leu Leu Ser Lys Met Leu Val Ile 290 295 300 Asp Ala Ser Lys Arg Ile Ser Val Asp Glu Ala Leu Gln His Pro Tyr 305 310 315 320 Ile Asn Val Trp Tyr Asp Pro Ser Glu Ala Glu Ala Pro Pro Pro Lys 325 330 335 Ile Pro Asp Lys Gln Leu Asp Glu Arg Glu His Thr Ile Glu Glu Trp 340 345 350 Lys Glu Leu Ile Tyr Lys Glu Val Met Asp Leu Glu Glu Arg Thr Lys 355 360 365 Asn Gly Val Ile Arg Gly Gln Pro Ser Pro Leu Ala Gln Val Gln Gln 370 375 380 <210> SEQ ID NO 62 <211> LENGTH: 427 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 62 Met Ser Arg Ser Lys Arg Asp Asn Asn Phe Tyr Ser Val Glu Ile Gly 1 5 10 15 Asp Ser Thr Phe Thr Val Leu Lys Arg Tyr Gln Asn Leu Lys Pro Ile 20 25 30 Gly Ser Gly Ala Gln Gly Ile Val Cys Ala Ala Tyr Asp Ala Ile Leu 35 40 45 Glu Arg Asn Val Ala Ile Lys Lys Leu Ser Arg Pro Phe Gln Asn Gln 50 55 60 Thr His Ala Lys Arg Ala Tyr Arg Glu Leu Val Leu Met Lys Cys Val 65 70 75 80 Asn His Lys Asn Ile Ile Gly Leu Leu Asn Val Phe Thr Pro Gln Lys 85 90 95 Ser Leu Glu Glu Phe Gln Asp Val Tyr Ile Val Met Glu Leu Met Asp 100 105 110 Ala Asn Leu Cys Gln Val Ile Gln Met Glu Leu Asp His Glu Arg Met 115 120 125 Ser Tyr Leu Leu Tyr Gln Met Leu Cys Gly Ile Lys His Leu His Ser 130 135 140 Ala Gly Ile Ile His Arg Asp Leu Lys Pro Ser Asn Ile Val Val Lys 145 150 155 160 Ser Asp Cys Thr Leu Lys Ile Leu Asp Phe Gly Leu Ala Arg Thr Ala 165 170 175 Gly Thr Ser Phe Met Met Thr Pro Tyr Val Val Thr Arg Tyr Tyr Arg 180 185 190 Ala Pro Glu Val Ile Leu Gly Met Gly Tyr Lys Glu Asn Val Asp Ile 195 200 205 Trp Ser Val Gly Cys Ile Met Gly Glu Met Ile Lys Gly Gly Val Leu 210 215 220 Phe Pro Gly Thr Asp His Ile Asp Gln Trp Asn Lys Val Ile Glu Gln 225 230 235 240 Leu Gly Thr Pro Cys Pro Glu Phe Met Lys Lys Leu Gln Pro Thr Val 245 250 255 Arg Thr Tyr Val Glu Asn Arg Pro Lys Tyr Ala Gly Tyr Ser Phe Glu 260 265 270 Lys Leu Phe Pro Asp Val Leu Phe Pro Ala Asp Ser Glu His Asn Lys 275 280 285 Leu Lys Ala Ser Gln Ala Arg Asp Leu Leu Ser Lys Met Leu Val Ile 290 295 300 Asp Ala Ser Lys Arg Ile Ser Val Asp Glu Ala Leu Gln His Pro Tyr 305 310 315 320 Ile Asn Val Trp Tyr Asp Pro Ser Glu Ala Glu Ala Pro Pro Pro Lys 325 330 335 Ile Pro Asp Lys Gln Leu Asp Glu Arg Glu His Thr Ile Glu Glu Trp 340 345 350 Lys Glu Leu Ile Tyr Lys Glu Val Met Asp Leu Glu Glu Arg Thr Lys 355 360 365 Asn Gly Val Ile Arg Gly Gln Pro Ser Pro Leu Gly Ala Ala Val Ile 370 375 380 Asn Gly Ser Gln His Pro Ser Ser Ser Ser Ser Val Asn Asp Val Ser 385 390 395 400 Ser Met Ser Thr Asp Pro Thr Leu Ala Ser Asp Thr Asp Ser Ser Leu 405 410 415 Glu Ala Ala Ala Gly Pro Leu Gly Cys Cys Arg 420 425 <210> SEQ ID NO 63 <211> LENGTH: 360 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 63 Met Ser Gln Glu Arg Pro Thr Phe Tyr Arg Gln Glu Leu Asn Lys Thr 1 5 10 15 Ile Trp Glu Val Pro Glu Arg Tyr Gln Asn Leu Ser Pro Val Gly Ser 20 25 30 Gly Ala Tyr Gly Ser Val Cys Ala Ala Phe Asp Thr Lys Thr Gly Leu 35 40 45 Arg Val Ala Val Lys Lys Leu Ser Arg Pro Phe Gln Ser Ile Ile His 50 55 60 Ala Lys Arg Thr Tyr Arg Glu Leu Arg Leu Leu Lys His Met Lys His 65 70 75 80 Glu Asn Val Ile Gly Leu Leu Asp Val Phe Thr Pro Ala Arg Ser Leu 85 90 95 Glu Glu Phe Asn Asp Val Tyr Leu Val Thr His Leu Met Gly Ala Asp 100 105 110 Leu Asn Asn Ile Val Lys Cys Gln Lys Leu Thr Asp Asp His Val Gln 115 120 125 Phe Leu Ile Tyr Gln Ile Leu Arg Gly Leu Lys Tyr Ile His Ser Ala 130 135 140 Asp Ile Ile His Arg Asp Leu Lys Pro Ser Asn Leu Ala Val Asn Glu 145 150 155 160 Asp Cys Glu Leu Lys Ile Leu Asp Phe Gly Leu Ala Arg His Thr Asp 165 170 175 Asp Glu Met Thr Gly Tyr Val Ala Thr Arg Trp Tyr Arg Ala Pro Glu 180 185 190 Ile Met Leu Asn Trp Met His Tyr Asn Gln Thr Val Asp Ile Trp Ser 195 200 205 Val Gly Cys Ile Met Ala Glu Leu Leu Thr Gly Arg Thr Leu Phe Pro 210 215 220 Gly Thr Asp His Ile Asn Gln Leu Gln Gln Ile Met Arg Leu Thr Gly 225 230 235 240 Thr Pro Pro Ala Tyr Leu Ile Asn Arg Met Pro Ser His Glu Ala Arg 245 250 255 Asn Tyr Ile Gln Ser Leu Thr Gln Met Pro Lys Met Asn Phe Ala Asn 260 265 270 Val Phe Ile Gly Ala Asn Pro Leu Ala Val Asp Leu Leu Glu Lys Met 275 280 285 Leu Val Leu Asp Ser Asp Lys Arg Ile Thr Ala Ala Gln Ala Leu Ala 290 295 300 His Ala Tyr Phe Ala Gln Tyr His Asp Pro Asp Asp Glu Pro Val Ala 305 310 315 320 Asp Pro Tyr Asp Gln Ser Phe Glu Ser Arg Asp Leu Leu Ile Asp Glu 325 330 335 Trp Lys Ser Leu Thr Tyr Asp Glu Val Ile Ser Phe Val Pro Pro Pro 340 345 350 Leu Asp Gln Glu Glu Met Glu Ser 355 360 <210> SEQ ID NO 64 <211> LENGTH: 240 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 64 Met Glu Asp Tyr Thr Lys Ile Glu Lys Ile Gly Glu Gly Thr Tyr Gly 1 5 10 15 Val Val Tyr Lys Gly Arg His Lys Thr Thr Gly Gln Val Val Ala Met 20 25 30 Lys Lys Ile Arg Leu Glu Ser Glu Glu Glu Gly Val Pro Ser Thr Ala 35 40 45 Ile Arg Glu Ile Ser Leu Leu Lys Glu Leu Arg His Pro Asn Ile Val 50 55 60 Ser Leu Gln Asp Val Leu Met Gln Asp Ser Arg Leu Tyr Leu Ile Phe 65 70 75 80 Glu Phe Leu Ser Met Asp Leu Lys Lys Tyr Leu Asp Ser Ile Pro Pro 85 90 95 Gly Gln Tyr Met Asp Ser Ser Leu Val Lys Val Val Thr Leu Trp Tyr 100 105 110 Arg Ser Pro Glu Val Leu Leu Gly Ser Ala Arg Tyr Ser Thr Pro Val 115 120 125 Asp Ile Trp Ser Ile Gly Thr Ile Phe Ala Glu Leu Ala Thr Lys Lys 130 135 140 Pro Leu Phe His Gly Asp Ser Glu Ile Asp Gln Leu Phe Arg Ile Phe 145 150 155 160 Arg Ala Leu Gly Thr Pro Asn Asn Glu Val Trp Pro Glu Val Glu Ser 165 170 175 Leu Gln Asp Tyr Lys Asn Thr Phe Pro Lys Trp Lys Pro Gly Ser Leu 180 185 190 Ala Ser His Val Lys Asn Leu Asp Glu Asn Gly Leu Asp Leu Leu Ser 195 200 205 Lys Met Leu Ile Tyr Asp Pro Ala Lys Arg Ile Ser Gly Lys Met Ala 210 215 220 Leu Asn His Pro Tyr Phe Asn Asp Leu Asp Asn Gln Ile Lys Lys Met 225 230 235 240 <210> SEQ ID NO 65 <211> LENGTH: 432 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 65 Met Leu Gly Asn Ser Ala Pro Gly Pro Ala Thr Arg Glu Ala Gly Ser 1 5 10 15 Ala Leu Leu Ala Leu Gln Gln Thr Ala Leu Gln Glu Asp Gln Glu Asn 20 25 30 Ile Asn Pro Glu Lys Ala Ala Pro Val Gln Gln Pro Arg Thr Arg Ala 35 40 45 Ala Leu Ala Val Leu Lys Ser Gly Asn Pro Arg Gly Leu Ala Gln Gln 50 55 60 Gln Arg Pro Lys Thr Arg Arg Val Ala Pro Leu Lys Asp Leu Pro Val 65 70 75 80 Asn Asp Glu His Val Thr Val Pro Pro Trp Lys Ala Asn Ser Lys Gln 85 90 95 Pro Ala Phe Thr Ile His Val Asp Glu Ala Glu Lys Glu Ala Gln Lys 100 105 110 Lys Pro Ala Glu Ser Gln Lys Ile Glu Arg Glu Asp Ala Leu Ala Phe 115 120 125 Asn Ser Ala Ile Ser Leu Pro Gly Pro Arg Lys Pro Leu Val Pro Leu 130 135 140 Asp Tyr Pro Met Asp Gly Ser Phe Glu Ser Pro His Thr Met Asp Met 145 150 155 160 Ser Ile Val Leu Glu Asp Glu Lys Pro Val Ser Val Asn Glu Val Pro 165 170 175 Asp Tyr His Glu Asp Ile His Thr Tyr Leu Arg Glu Met Glu Val Lys 180 185 190 Cys Lys Pro Lys Val Gly Tyr Met Lys Lys Gln Pro Asp Ile Thr Asn 195 200 205 Ser Met Arg Ala Ile Leu Val Asp Trp Leu Val Glu Val Gly Glu Glu 210 215 220 Tyr Lys Leu Gln Asn Glu Thr Leu His Leu Ala Val Asn Tyr Ile Asp 225 230 235 240 Arg Phe Leu Ser Ser Met Ser Val Leu Arg Gly Lys Leu Gln Leu Val 245 250 255 Gly Thr Ala Ala Met Leu Leu Ala Ser Lys Phe Glu Glu Ile Tyr Pro 260 265 270 Pro Glu Val Ala Glu Phe Val Tyr Ile Thr Asp Asp Thr Tyr Thr Lys 275 280 285 Lys Gln Val Leu Arg Met Glu His Leu Val Leu Lys Val Leu Thr Phe 290 295 300 Asp Leu Ala Ala Pro Thr Val Asn Gln Phe Leu Thr Gln Tyr Phe Leu 305 310 315 320 His Gln Gln Pro Ala Asn Cys Lys Val Glu Ser Leu Ala Met Phe Leu 325 330 335 Gly Glu Leu Ser Leu Ile Asp Ala Asp Pro Tyr Leu Lys Tyr Leu Pro 340 345 350 Ser Val Ile Ala Gly Ala Ala Phe His Leu Ala Leu Tyr Thr Val Thr 355 360 365 Gly Gln Ser Trp Pro Glu Ser Leu Ile Arg Lys Thr Gly Tyr Thr Leu 370 375 380 Glu Ser Leu Lys Pro Cys Leu Met Asp Leu His Gln Thr Tyr Leu Lys 385 390 395 400 Ala Pro Gln His Ala Gln Gln Ser Ile Arg Glu Lys Tyr Lys Asn Ser 405 410 415 Lys Tyr His Gly Val Ser Leu Leu Asn Pro Pro Glu Thr Leu Asn Leu 420 425 430 <210> SEQ ID NO 66 <211> LENGTH: 289 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 66 Met Glu Leu Leu Cys His Glu Val Asp Pro Val Arg Arg Ala Val Arg 1 5 10 15 Asp Arg Asn Leu Leu Arg Asp Asp Arg Val Leu Gln Asn Leu Leu Thr 20 25 30 Ile Glu Glu Arg Tyr Leu Pro Gln Cys Ser Tyr Phe Lys Cys Val Gln 35 40 45 Lys Asp Ile Gln Pro Tyr Met Arg Arg Met Val Ala Thr Trp Met Leu 50 55 60 Glu Val Cys Glu Glu Gln Lys Cys Glu Glu Glu Val Phe Pro Leu Ala 65 70 75 80 Met Asn Tyr Leu Asp Arg Phe Leu Ala Gly Val Pro Thr Pro Lys Ser 85 90 95 His Leu Gln Leu Leu Gly Ala Val Cys Met Phe Leu Ala Ser Lys Leu 100 105 110 Lys Glu Thr Ser Pro Leu Thr Ala Glu Lys Leu Cys Ile Tyr Thr Asp 115 120 125 Asn Ser Ile Lys Pro Gln Glu Leu Leu Glu Trp Glu Leu Val Val Leu 130 135 140 Gly Lys Leu Lys Trp Asn Leu Ala Ala Val Thr Pro His Asp Phe Ile 145 150 155 160 Glu His Ile Leu Arg Lys Leu Pro Gln Gln Arg Glu Lys Leu Ser Leu 165 170 175 Ile Arg Lys His Ala Gln Thr Phe Ile Ala Leu Cys Ala Thr Asp Phe 180 185 190 Lys Phe Ala Met Tyr Pro Pro Ser Met Ile Ala Thr Gly Ser Val Gly 195 200 205 Ala Ala Ile Cys Gly Leu Gln Gln Asp Glu Glu Val Ser Ser Leu Thr 210 215 220 Cys Asp Ala Leu Thr Glu Leu Leu Ala Lys Ile Thr Asn Thr Asp Val 225 230 235 240 Asp Cys Leu Lys Ala Cys Gln Glu Gln Ile Glu Ala Val Leu Leu Asn 245 250 255 Ser Leu Gln Gln Tyr Arg Gln Asp Gln Arg Asp Gly Ser Lys Ser Glu 260 265 270 Asp Glu Leu Asp Gln Ala Ser Thr Pro Thr Asp Val Arg Asp Ile Asp 275 280 285 Leu <210> SEQ ID NO 67 <211> LENGTH: 292 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 67 Met Glu Leu Leu Cys Cys Glu Gly Thr Arg His Ala Pro Arg Ala Gly 1 5 10 15 Pro Asp Pro Arg Leu Leu Gly Asp Gln Arg Val Leu Gln Ser Leu Leu 20 25 30 Arg Leu Glu Glu Arg Tyr Val Pro Arg Ala Ser Tyr Phe Gln Cys Val 35 40 45 Gln Arg Glu Ile Lys Pro His Met Arg Lys Met Leu Ala Tyr Trp Met 50 55 60 Leu Glu Val Cys Glu Glu Gln Arg Cys Glu Glu Glu Val Phe Pro Leu 65 70 75 80 Ala Met Asn Tyr Leu Asp Arg Tyr Leu Ser Cys Val Pro Thr Arg Lys 85 90 95 Ala Gln Leu Gln Leu Leu Gly Ala Val Cys Met Leu Leu Ala Ser Lys 100 105 110 Leu Arg Glu Thr Thr Pro Leu Thr Ile Glu Lys Leu Cys Ile Tyr Thr 115 120 125 Asp His Ala Val Ser Pro Arg Gln Leu Arg Asp Trp Glu Val Leu Val 130 135 140 Leu Gly Lys Leu Lys Trp Asp Leu Ala Ala Val Ile Ala His Asp Phe 145 150 155 160 Leu Ala Phe Ile Leu His Arg Leu Ser Leu Pro Arg Asp Arg Gln Ala 165 170 175 Leu Val Lys Lys His Ala Gln Thr Phe Leu Ala Leu Cys Ala Thr Asp 180 185 190 Tyr Thr Phe Ala Met Tyr Pro Pro Ser Met Ile Ala Thr Gly Ser Ile 195 200 205 Gly Ala Ala Val Gln Gly Leu Gly Ala Cys Ser Met Ser Gly Asp Glu 210 215 220 Leu Thr Glu Leu Leu Ala Gly Ile Thr Gly Thr Glu Val Asp Cys Leu 225 230 235 240 Arg Ala Cys Gln Glu Gln Ile Glu Ala Ala Leu Arg Glu Ser Leu Arg 245 250 255 Glu Ala Ser Gln Thr Ser Ser Ser Pro Ala Pro Lys Ala Pro Arg Gly 260 265 270 Ser Ser Ser Gln Gly Pro Ser Gln Thr Ser Thr Pro Thr Asp Val Thr 275 280 285 Ala Ile His Leu 290 <210> SEQ ID NO 68 <211> LENGTH: 410 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 68 Met Pro Arg Glu Arg Arg Glu Arg Asp Ala Lys Glu Arg Asp Thr Met 1 5 10 15 Lys Glu Asp Gly Gly Ala Glu Phe Ser Ala Arg Ser Arg Lys Arg Lys 20 25 30 Ala Asn Val Thr Val Phe Leu Gln Asp Pro Asp Glu Glu Met Ala Lys 35 40 45 Ile Asp Arg Thr Ala Arg Asp Gln Cys Gly Ser Gln Pro Trp Asp Asn 50 55 60 Asn Ala Val Cys Ala Asp Pro Cys Ser Leu Ile Pro Thr Pro Asp Lys 65 70 75 80 Glu Asp Asp Asp Arg Val Tyr Pro Asn Ser Thr Cys Lys Pro Arg Ile 85 90 95 Ile Ala Pro Ser Arg Gly Ser Pro Leu Pro Val Leu Ser Trp Ala Asn 100 105 110 Arg Glu Glu Val Trp Lys Ile Met Leu Asn Lys Glu Lys Thr Tyr Leu 115 120 125 Arg Asp Gln His Phe Leu Glu Gln His Pro Leu Leu Gln Pro Lys Met 130 135 140 Arg Ala Ile Leu Leu Asp Trp Leu Met Glu Val Cys Glu Val Tyr Lys 145 150 155 160 Leu His Arg Glu Thr Phe Tyr Leu Ala Gln Asp Phe Phe Asp Arg Tyr 165 170 175 Met Ala Thr Gln Glu Asn Val Val Lys Thr Leu Leu Gln Leu Ile Gly 180 185 190 Ile Ser Ser Leu Phe Ile Ala Ala Lys Leu Glu Glu Ile Tyr Pro Pro 195 200 205 Lys Leu His Gln Phe Ala Tyr Val Thr Asp Gly Ala Cys Ser Gly Asp 210 215 220 Glu Ile Leu Thr Met Glu Leu Met Ile Met Lys Ala Leu Lys Trp Arg 225 230 235 240 Leu Ser Pro Leu Thr Ile Val Ser Trp Leu Asn Val Tyr Met Gln Val 245 250 255 Ala Tyr Leu Asn Asp Leu His Glu Val Leu Leu Pro Gln Tyr Pro Gln 260 265 270 Gln Ile Phe Ile Gln Ile Ala Glu Leu Leu Asp Leu Cys Val Leu Asp 275 280 285 Val Asp Cys Leu Glu Phe Pro Tyr Gly Ile Leu Ala Ala Ser Ala Leu 290 295 300 Tyr His Phe Ser Ser Ser Glu Leu Met Gln Lys Val Ser Gly Tyr Gln 305 310 315 320 Trp Cys Asp Ile Glu Asn Cys Val Lys Trp Met Val Pro Phe Ala Met 325 330 335 Val Ile Arg Glu Thr Gly Ser Ser Lys Leu Lys His Phe Arg Gly Val 340 345 350 Ala Asp Glu Asp Ala His Asn Ile Gln Thr His Arg Asp Ser Leu Asp 355 360 365 Leu Leu Asp Lys Ala Arg Ala Lys Lys Ala Met Leu Ser Glu Gln Asn 370 375 380 Arg Ala Ser Pro Leu Pro Ser Gly Leu Leu Thr Pro Pro Gln Ser Gly 385 390 395 400 Lys Lys Gln Ser Ser Gly Pro Glu Met Ala 405 410 <210> SEQ ID NO 69 <211> LENGTH: 473 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 69 Met Ser Thr Glu Leu Phe Ser Ser Thr Arg Glu Glu Gly Ser Ser Gly 1 5 10 15 Ser Gly Pro Ser Phe Arg Ser Asn Gln Arg Lys Met Leu Asn Leu Leu 20 25 30 Leu Glu Arg Asp Thr Ser Phe Thr Val Cys Pro Asp Val Pro Arg Thr 35 40 45 Pro Val Gly Lys Phe Leu Gly Asp Ser Ala Asn Leu Ser Ile Leu Ser 50 55 60 Gly Gly Thr Pro Lys Arg Cys Leu Asp Leu Ser Asn Leu Ser Ser Gly 65 70 75 80 Glu Ile Thr Ala Thr Gln Leu Thr Thr Ser Ala Asp Leu Asp Glu Thr 85 90 95 Gly His Leu Asp Ser Ser Gly Leu Gln Glu Val His Leu Ala Gly Met 100 105 110 Asn His Asp Gln His Leu Met Lys Cys Ser Pro Ala Gln Leu Leu Cys 115 120 125 Ser Thr Pro Asn Gly Leu Asp Arg Gly His Arg Lys Arg Asp Ala Met 130 135 140 Cys Ser Ser Ser Ala Asn Lys Glu Asn Asp Asn Gly Asn Leu Val Asp 145 150 155 160 Ser Glu Met Lys Tyr Leu Gly Ser Pro Ile Thr Thr Val Pro Lys Leu 165 170 175 Asp Lys Asn Pro Asn Leu Gly Glu Asp Gln Ala Glu Glu Ile Ser Asp 180 185 190 Glu Leu Met Glu Phe Ser Leu Lys Asp Gln Glu Ala Lys Val Ser Arg 195 200 205 Ser Gly Leu Tyr Arg Ser Pro Ser Met Pro Glu Asn Leu Asn Arg Pro 210 215 220 Arg Leu Lys Gln Val Glu Lys Phe Lys Asp Asn Thr Ile Pro Asp Lys 225 230 235 240 Val Lys Lys Lys Tyr Phe Ser Gly Gln Gly Lys Leu Arg Lys Gly Leu 245 250 255 Cys Leu Lys Lys Thr Val Ser Leu Cys Asp Ile Thr Ile Thr Gln Met 260 265 270 Leu Glu Glu Asp Ser Asn Gln Gly His Leu Ile Gly Asp Phe Ser Lys 275 280 285 Val Cys Ala Leu Pro Thr Val Ser Gly Lys His Gln Asp Leu Lys Tyr 290 295 300 Val Asn Pro Glu Thr Val Ala Ala Leu Leu Ser Gly Lys Phe Gln Gly 305 310 315 320 Leu Ile Glu Lys Phe Tyr Val Ile Asp Cys Arg Tyr Pro Tyr Glu Tyr 325 330 335 Leu Gly Gly His Ile Gln Gly Ala Leu Asn Leu Tyr Ser Gln Glu Glu 340 345 350 Leu Phe Asn Phe Phe Leu Lys Lys Pro Ile Val Pro Leu Asp Thr Gln 355 360 365 Lys Arg Ile Ile Ile Val Phe His Cys Glu Phe Ser Ser Glu Arg Gly 370 375 380 Pro Arg Met Cys Arg Cys Leu Arg Glu Glu Asp Arg Ser Leu Asn Gln 385 390 395 400 Tyr Pro Ala Leu Tyr Tyr Pro Glu Leu Tyr Ile Leu Lys Gly Gly Tyr 405 410 415 Arg Asp Phe Phe Pro Glu Tyr Met Glu Leu Cys Glu Pro Gln Ser Tyr 420 425 430 Cys Pro Met His His Gln Asp His Lys Thr Glu Leu Leu Arg Cys Arg 435 440 445 Ser Gln Ser Lys Val Gln Glu Gly Glu Arg Gln Leu Arg Glu Gln Ile 450 455 460 Ala Leu Leu Val Lys Asp Met Ser Pro 465 470 <210> SEQ ID NO 70 <211> LENGTH: 400 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 70 Met Ser Thr Glu Leu Phe Ser Ser Thr Arg Glu Glu Gly Ser Ser Gly 1 5 10 15 Ser Gly Pro Ser Phe Arg Ser Asn Gln Arg Lys Met Leu Asn Leu Leu 20 25 30 Leu Glu Arg Asp Thr Ser Phe Thr Val Cys Pro Asp Val Pro Arg Thr 35 40 45 Pro Val Gly Lys Phe Leu Gly Asp Ser Ala Asn Leu Ser Ile Leu Ser 50 55 60 Gly Ser Pro Gly Phe Phe Arg Thr Ser Gly Ser Ala Phe Ser Trp Asp 65 70 75 80 Asp Asn Gly Asn Leu Val Asp Ser Glu Met Lys Tyr Leu Gly Ser Pro 85 90 95 Ile Thr Thr Val Pro Lys Leu Asp Lys Asn Pro Asn Leu Gly Glu Asp 100 105 110 Gln Ala Glu Glu Ile Ser Asp Glu Leu Met Glu Phe Ser Leu Lys Asp 115 120 125 Gln Glu Ala Lys Val Ser Arg Ser Gly Leu Tyr Arg Ser Pro Ser Met 130 135 140 Pro Glu Asn Leu Asn Arg Pro Arg Leu Lys Gln Val Glu Lys Phe Lys 145 150 155 160 Asp Asn Thr Ile Pro Asp Lys Val Lys Lys Lys Tyr Phe Ser Gly Gln 165 170 175 Gly Lys Leu Arg Lys Gly Leu Cys Leu Lys Lys Thr Val Ser Leu Cys 180 185 190 Asp Ile Thr Ile Thr Gln Met Leu Glu Glu Asp Ser Asn Gln Gly His 195 200 205 Leu Ile Gly Asp Phe Ser Lys Val Cys Ala Leu Pro Thr Val Ser Gly 210 215 220 Lys His Gln Asp Leu Lys Tyr Val Asn Pro Glu Thr Val Ala Ala Leu 225 230 235 240 Leu Ser Gly Lys Phe Gln Gly Leu Ile Glu Lys Phe Tyr Val Ile Asp 245 250 255 Cys Arg Tyr Pro Tyr Glu Tyr Leu Gly Gly His Ile Gln Gly Ala Leu 260 265 270 Asn Leu Tyr Ser Gln Glu Glu Leu Phe Asn Phe Phe Leu Lys Lys Pro 275 280 285 Ile Val Pro Leu Asp Thr Gln Lys Arg Ile Ile Ile Val Phe His Cys 290 295 300 Glu Phe Ser Ser Glu Arg Gly Pro Arg Met Cys Arg Cys Leu Arg Glu 305 310 315 320 Glu Asp Arg Ser Leu Asn Gln Tyr Pro Ala Leu Tyr Tyr Pro Glu Leu 325 330 335 Tyr Ile Leu Lys Gly Gly Tyr Arg Asp Phe Phe Pro Glu Tyr Met Glu 340 345 350 Leu Cys Glu Pro Gln Ser Tyr Cys Pro Met His His Gln Asp His Lys 355 360 365 Thr Glu Leu Leu Arg Cys Arg Ser Gln Ser Lys Val Gln Glu Gly Glu 370 375 380 Arg Gln Leu Arg Glu Gln Ile Ala Leu Leu Val Lys Asp Met Ser Pro 385 390 395 400 <210> SEQ ID NO 71 <211> LENGTH: 164 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 71 Met Ser Glu Pro Ala Gly Asp Val Arg Gln Asn Pro Cys Gly Ser Lys 1 5 10 15 Ala Cys Arg Arg Leu Phe Gly Pro Val Asp Ser Glu Gln Leu Ser Arg 20 25 30 Asp Cys Asp Ala Leu Met Ala Gly Cys Ile Gln Glu Ala Arg Glu Arg 35 40 45 Trp Asn Phe Asp Phe Val Thr Glu Thr Pro Leu Glu Gly Asp Phe Ala 50 55 60 Trp Glu Arg Val Arg Gly Leu Gly Leu Pro Lys Leu Tyr Leu Pro Thr 65 70 75 80 Gly Pro Arg Arg Gly Arg Asp Glu Leu Gly Gly Gly Arg Arg Pro Gly 85 90 95 Thr Ser Pro Ala Leu Leu Gln Gly Thr Ala Glu Glu Asp His Val Asp 100 105 110 Leu Ser Leu Ser Cys Thr Leu Val Pro Arg Ser Gly Glu Gln Ala Glu 115 120 125 Gly Ser Pro Gly Gly Pro Gly Asp Ser Gln Gly Arg Lys Arg Arg Gln 130 135 140 Thr Ser Met Thr Asp Phe Tyr His Ser Lys Arg Arg Leu Ile Phe Ser 145 150 155 160 Lys Arg Lys Pro <210> SEQ ID NO 72 <211> LENGTH: 156 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 72 Met Glu Pro Ala Ala Gly Ser Ser Met Glu Pro Ser Ala Asp Trp Leu 1 5 10 15 Ala Thr Ala Ala Ala Arg Gly Arg Val Glu Glu Val Arg Ala Leu Leu 20 25 30 Glu Ala Gly Ala Leu Pro Asn Ala Pro Asn Ser Tyr Gly Arg Arg Pro 35 40 45 Ile Gln Val Met Met Met Gly Ser Ala Arg Val Ala Glu Leu Leu Leu 50 55 60 Leu His Gly Ala Glu Pro Asn Cys Ala Asp Pro Ala Thr Leu Thr Arg 65 70 75 80 Pro Val His Asp Ala Ala Arg Glu Gly Phe Leu Asp Thr Leu Val Val 85 90 95 Leu His Arg Ala Gly Ala Arg Leu Asp Val Arg Asp Ala Trp Gly Arg 100 105 110 Leu Pro Val Asp Leu Ala Glu Glu Leu Gly His Arg Asp Val Ala Arg 115 120 125 Tyr Leu Arg Ala Ala Ala Gly Gly Thr Arg Gly Ser Asn His Ala Arg 130 135 140 Ile Asp Ala Ala Glu Gly Pro Ser Asp Ile Pro Asp 145 150 155 <210> SEQ ID NO 73 <211> LENGTH: 116 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 73 Met Glu Pro Ala Ala Gly Ser Ser Met Glu Pro Ser Ala Asp Trp Leu 1 5 10 15 Ala Thr Ala Ala Ala Arg Gly Arg Val Glu Glu Val Arg Ala Leu Leu 20 25 30 Glu Ala Gly Ala Leu Pro Asn Ala Pro Asn Ser Tyr Gly Arg Arg Pro 35 40 45 Ile Gln Val Gly Arg Gly Ser Ala Ala Gly Ala Gly Asp Gly Gly Arg 50 55 60 Leu Trp Arg Thr Lys Phe Ala Gly Glu Leu Glu Ser Gly Ser Ala Ser 65 70 75 80 Ile Leu Arg Lys Lys Gly Arg Leu Pro Gly Glu Phe Ser Glu Gly Val 85 90 95 Cys Asn His Arg Pro Pro Pro Gly Asp Ala Leu Gly Ala Trp Glu Ala 100 105 110 Lys Glu Glu Glu 115 <210> SEQ ID NO 74 <211> LENGTH: 173 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 74 Met Gly Arg Gly Arg Cys Val Gly Pro Ser Leu Gln Leu Arg Gly Gln 1 5 10 15 Glu Trp Arg Cys Ser Pro Leu Val Pro Lys Gly Gly Ala Ala Ala Ala 20 25 30 Glu Leu Gly Pro Gly Gly Gly Glu Asn Met Val Arg Arg Phe Leu Val 35 40 45 Thr Leu Arg Ile Arg Arg Ala Cys Gly Pro Pro Arg Val Arg Val Phe 50 55 60 Val Val His Ile Pro Arg Leu Thr Gly Glu Trp Ala Ala Pro Gly Ala 65 70 75 80 Pro Ala Ala Val Ala Leu Val Leu Met Leu Leu Arg Ser Gln Arg Leu 85 90 95 Gly Gln Gln Pro Leu Pro Arg Arg Pro Gly His Asp Asp Gly Gln Arg 100 105 110 Pro Ser Gly Gly Ala Ala Ala Ala Pro Arg Arg Gly Ala Gln Leu Arg 115 120 125 Arg Pro Arg His Ser His Pro Thr Arg Ala Arg Arg Cys Pro Gly Gly 130 135 140 Leu Pro Gly His Ala Gly Gly Ala Ala Pro Gly Arg Gly Ala Ala Gly 145 150 155 160 Arg Ala Arg Cys Leu Gly Pro Ser Ala Arg Gly Pro Gly 165 170 <210> SEQ ID NO 75 <211> LENGTH: 298 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 75 Met Glu Asn Phe Gln Lys Val Glu Lys Ile Gly Glu Gly Thr Tyr Gly 1 5 10 15 Val Val Tyr Lys Ala Arg Asn Lys Leu Thr Gly Glu Val Val Ala Leu 20 25 30 Lys Lys Ile Arg Leu Asp Thr Glu Thr Glu Gly Val Pro Ser Thr Ala 35 40 45 Ile Arg Glu Ile Ser Leu Leu Lys Glu Leu Asn His Pro Asn Ile Val 50 55 60 Lys Leu Leu Asp Val Ile His Thr Glu Asn Lys Leu Tyr Leu Val Phe 65 70 75 80 Glu Phe Leu His Gln Asp Leu Lys Lys Phe Met Asp Ala Ser Ala Leu 85 90 95 Thr Gly Ile Pro Leu Pro Leu Ile Lys Ser Tyr Leu Phe Gln Leu Leu 100 105 110 Gln Gly Leu Ala Phe Cys His Ser His Arg Val Leu His Arg Asp Leu 115 120 125 Lys Pro Gln Asn Leu Leu Ile Asn Thr Glu Gly Ala Ile Lys Leu Ala 130 135 140 Asp Phe Gly Leu Ala Arg Ala Phe Gly Val Pro Val Arg Thr Tyr Thr 145 150 155 160 His Glu Val Val Thr Leu Trp Tyr Arg Ala Pro Glu Ile Leu Leu Gly 165 170 175 Cys Lys Tyr Tyr Ser Thr Ala Val Asp Ile Trp Ser Leu Gly Cys Ile 180 185 190 Phe Ala Glu Met Val Thr Arg Arg Ala Leu Phe Pro Gly Asp Ser Glu 195 200 205 Ile Asp Gln Leu Phe Arg Ile Phe Arg Thr Leu Gly Thr Pro Asp Glu 210 215 220 Val Val Trp Pro Gly Val Thr Ser Met Pro Asp Tyr Lys Pro Ser Phe 225 230 235 240 Pro Lys Trp Ala Arg Gln Asp Phe Ser Lys Val Val Pro Pro Leu Asp 245 250 255 Glu Asp Gly Arg Ser Leu Leu Ser Gln Met Leu His Tyr Asp Pro Asn 260 265 270 Lys Arg Ile Ser Ala Lys Ala Ala Leu Ala His Pro Phe Phe Gln Asp 275 280 285 Val Thr Lys Pro Val Pro His Leu Arg Leu 290 295 <210> SEQ ID NO 76 <211> LENGTH: 264 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 76 Met Glu Asn Phe Gln Lys Val Glu Lys Ile Gly Glu Gly Thr Tyr Gly 1 5 10 15 Val Val Tyr Lys Ala Arg Asn Lys Leu Thr Gly Glu Val Val Ala Leu 20 25 30 Lys Lys Ile Arg Leu Asp Thr Glu Thr Glu Gly Val Pro Ser Thr Ala 35 40 45 Ile Arg Glu Ile Ser Leu Leu Lys Glu Leu Asn His Pro Asn Ile Val 50 55 60 Lys Leu Leu Asp Val Ile His Thr Glu Asn Lys Leu Tyr Leu Val Phe 65 70 75 80 Glu Phe Leu His Gln Asp Leu Lys Lys Phe Met Asp Ala Ser Ala Leu 85 90 95 Thr Gly Ile Pro Leu Pro Leu Ile Lys Ser Tyr Leu Phe Gln Leu Leu 100 105 110 Gln Gly Leu Ala Phe Cys His Ser His Arg Val Leu His Arg Asp Leu 115 120 125 Lys Pro Gln Asn Leu Leu Ile Asn Thr Glu Gly Ala Ile Lys Leu Ala 130 135 140 Asp Phe Gly Leu Ala Arg Ala Phe Gly Val Pro Val Arg Thr Tyr Thr 145 150 155 160 His Glu Val Thr Arg Arg Ala Leu Phe Pro Gly Asp Ser Glu Ile Asp 165 170 175 Gln Leu Phe Arg Ile Phe Arg Thr Leu Gly Thr Pro Asp Glu Val Val 180 185 190 Trp Pro Gly Val Thr Ser Met Pro Asp Tyr Lys Pro Ser Phe Pro Lys 195 200 205 Trp Ala Arg Gln Asp Phe Ser Lys Val Val Pro Pro Leu Asp Glu Asp 210 215 220 Gly Arg Ser Leu Leu Ser Gln Met Leu His Tyr Asp Pro Asn Lys Arg 225 230 235 240 Ile Ser Ala Lys Ala Ala Leu Ala His Pro Phe Phe Gln Asp Val Thr 245 250 255 Lys Pro Val Pro His Leu Arg Leu 260 <210> SEQ ID NO 77 <211> LENGTH: 303 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 77 Met Ala Thr Ser Arg Tyr Glu Pro Val Ala Glu Ile Gly Val Gly Ala 1 5 10 15 Tyr Gly Thr Val Tyr Lys Ala Arg Asp Pro His Ser Gly His Phe Val 20 25 30 Ala Leu Lys Ser Val Arg Val Pro Asn Gly Gly Gly Gly Gly Gly Gly 35 40 45 Leu Pro Ile Ser Thr Val Arg Glu Val Ala Leu Leu Arg Arg Leu Glu 50 55 60 Ala Phe Glu His Pro Asn Val Val Arg Leu Met Asp Val Cys Ala Thr 65 70 75 80 Ser Arg Thr Asp Arg Glu Ile Lys Val Thr Leu Val Phe Glu His Val 85 90 95 Asp Gln Asp Leu Arg Thr Tyr Leu Asp Lys Ala Pro Pro Pro Gly Leu 100 105 110 Pro Ala Glu Thr Ile Lys Asp Leu Met Arg Gln Phe Leu Arg Gly Leu 115 120 125 Asp Phe Leu His Ala Asn Cys Ile Val His Arg Asp Leu Lys Pro Glu 130 135 140 Asn Ile Leu Val Thr Ser Gly Gly Thr Val Lys Leu Ala Asp Phe Gly 145 150 155 160 Leu Ala Arg Ile Tyr Ser Tyr Gln Met Ala Leu Thr Pro Val Val Val 165 170 175 Thr Leu Trp Tyr Arg Ala Pro Glu Val Leu Leu Gln Ser Thr Tyr Ala 180 185 190 Thr Pro Val Asp Met Trp Ser Val Gly Cys Ile Phe Ala Glu Met Phe 195 200 205 Arg Arg Lys Pro Leu Phe Cys Gly Asn Ser Glu Ala Asp Gln Leu Gly 210 215 220 Lys Ile Phe Asp Leu Ile Gly Leu Pro Pro Glu Asp Asp Trp Pro Arg 225 230 235 240 Asp Val Ser Leu Pro Arg Gly Ala Phe Pro Pro Arg Gly Pro Arg Pro 245 250 255 Val Gln Ser Val Val Pro Glu Met Glu Glu Ser Gly Ala Gln Leu Leu 260 265 270 Leu Glu Met Leu Thr Phe Asn Pro His Lys Arg Ile Ser Ala Phe Arg 275 280 285 Ala Leu Gln His Ser Tyr Leu His Lys Asp Glu Gly Asn Pro Glu 290 295 300 <210> SEQ ID NO 78 <211> LENGTH: 326 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 78 Met Glu Lys Asp Gly Leu Cys Arg Ala Asp Gln Gln Tyr Glu Cys Val 1 5 10 15 Ala Glu Ile Gly Glu Gly Ala Tyr Gly Lys Val Phe Lys Ala Arg Asp 20 25 30 Leu Lys Asn Gly Gly Arg Phe Val Ala Leu Lys Arg Val Arg Val Gln 35 40 45 Thr Gly Glu Glu Gly Met Pro Leu Ser Thr Ile Arg Glu Val Ala Val 50 55 60 Leu Arg His Leu Glu Thr Phe Glu His Pro Asn Val Val Arg Leu Phe 65 70 75 80 Asp Val Cys Thr Val Ser Arg Thr Asp Arg Glu Thr Lys Leu Thr Leu 85 90 95 Val Phe Glu His Val Asp Gln Asp Leu Thr Thr Tyr Leu Asp Lys Val 100 105 110 Pro Glu Pro Gly Val Pro Thr Glu Thr Ile Lys Asp Met Met Phe Gln 115 120 125 Leu Leu Arg Gly Leu Asp Phe Leu His Ser His Arg Val Val His Arg 130 135 140 Asp Leu Lys Pro Gln Asn Ile Leu Val Thr Ser Ser Gly Gln Ile Lys 145 150 155 160 Leu Ala Asp Phe Gly Leu Ala Arg Ile Tyr Ser Phe Gln Met Ala Leu 165 170 175 Thr Ser Val Val Val Thr Leu Trp Tyr Arg Ala Pro Glu Val Leu Leu 180 185 190 Gln Ser Ser Tyr Ala Thr Pro Val Asp Leu Trp Ser Val Gly Cys Ile 195 200 205 Phe Ala Glu Met Phe Arg Arg Lys Pro Leu Phe Arg Gly Ser Ser Asp 210 215 220 Val Asp Gln Leu Gly Lys Ile Leu Asp Val Ile Gly Leu Pro Gly Glu 225 230 235 240 Glu Asp Trp Pro Arg Asp Val Ala Leu Pro Arg Gln Ala Phe His Ser 245 250 255 Lys Ser Ala Gln Pro Ile Glu Lys Phe Val Thr Asp Ile Asp Glu Leu 260 265 270 Gly Lys Asp Leu Leu Leu Lys Cys Leu Thr Phe Asn Pro Ala Lys Arg 275 280 285 Ile Ser Ala Tyr Ser Ala Leu Ser His Pro Tyr Phe Gln Asp Leu Glu 290 295 300 Arg Cys Lys Glu Asn Leu Asp Ser His Leu Pro Pro Ser Gln Asn Thr 305 310 315 320 Ser Glu Leu Asn Thr Ala 325 <210> SEQ ID NO 79 <211> LENGTH: 437 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 79 Met Ala Leu Ala Gly Ala Pro Ala Gly Gly Pro Cys Ala Pro Ala Leu 1 5 10 15 Glu Ala Leu Leu Gly Ala Gly Ala Leu Arg Leu Leu Asp Ser Ser Gln 20 25 30 Ile Val Ile Ile Ser Ala Ala Gln Asp Ala Ser Ala Pro Pro Ala Pro 35 40 45 Thr Gly Pro Ala Ala Pro Ala Ala Gly Pro Cys Asp Pro Asp Leu Leu 50 55 60 Leu Phe Ala Thr Pro Gln Ala Pro Arg Pro Thr Pro Ser Ala Pro Arg 65 70 75 80 Pro Ala Leu Gly Arg Pro Pro Val Lys Arg Arg Leu Asp Leu Glu Thr 85 90 95 Asp His Gln Tyr Leu Ala Glu Ser Ser Gly Pro Ala Arg Gly Arg Gly 100 105 110 Arg His Pro Gly Lys Gly Val Lys Ser Pro Gly Glu Lys Ser Arg Tyr 115 120 125 Glu Thr Ser Leu Asn Leu Thr Thr Lys Arg Phe Leu Glu Leu Leu Ser 130 135 140 His Ser Ala Asp Gly Val Val Asp Leu Asn Trp Ala Ala Glu Val Leu 145 150 155 160 Lys Val Gln Lys Arg Arg Ile Tyr Asp Ile Thr Asn Val Leu Glu Gly 165 170 175 Ile Gln Leu Ile Ala Lys Lys Ser Lys Asn His Ile Gln Trp Leu Gly 180 185 190 Ser His Thr Thr Val Gly Val Gly Gly Arg Leu Glu Gly Leu Thr Gln 195 200 205 Asp Leu Arg Gln Leu Gln Glu Ser Glu Gln Gln Leu Asp His Leu Met 210 215 220 Asn Ile Cys Thr Thr Gln Leu Arg Leu Leu Ser Glu Asp Thr Asp Ser 225 230 235 240 Gln Arg Leu Ala Tyr Val Thr Cys Gln Asp Leu Arg Ser Ile Ala Asp 245 250 255 Pro Ala Glu Gln Met Val Met Val Ile Lys Ala Pro Pro Glu Thr Gln 260 265 270 Leu Gln Ala Val Asp Ser Ser Glu Asn Phe Gln Ile Ser Leu Lys Ser 275 280 285 Lys Gln Gly Pro Ile Asp Val Phe Leu Cys Pro Glu Glu Thr Val Gly 290 295 300 Gly Ile Ser Pro Gly Lys Thr Pro Ser Gln Glu Val Thr Ser Glu Glu 305 310 315 320 Glu Asn Arg Ala Thr Asp Ser Ala Thr Ile Val Ser Pro Pro Pro Ser 325 330 335 Ser Pro Pro Ser Ser Leu Thr Thr Asp Pro Ser Gln Ser Leu Leu Ser 340 345 350 Leu Glu Gln Glu Pro Leu Leu Ser Arg Met Gly Ser Leu Arg Ala Pro 355 360 365 Val Asp Glu Asp Arg Leu Ser Pro Leu Val Ala Ala Asp Ser Leu Leu 370 375 380 Glu His Val Arg Glu Asp Phe Ser Gly Leu Leu Pro Glu Glu Phe Ile 385 390 395 400 Ser Leu Ser Pro Pro His Glu Ala Leu Asp Tyr His Phe Gly Leu Glu 405 410 415 Glu Gly Glu Gly Ile Arg Asp Leu Phe Asp Cys Asp Phe Gly Asp Leu 420 425 430 Thr Pro Leu Asp Phe 435 <210> SEQ ID NO 80 <211> LENGTH: 1170 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 80 Met Gly Leu Ala Trp Gly Leu Gly Val Leu Phe Leu Met His Val Cys 1 5 10 15 Gly Thr Asn Arg Ile Pro Glu Ser Gly Gly Asp Asn Ser Val Phe Asp 20 25 30 Ile Phe Glu Leu Thr Gly Ala Ala Arg Lys Gly Ser Gly Arg Arg Leu 35 40 45 Val Lys Gly Pro Asp Pro Ser Ser Pro Ala Phe Arg Ile Glu Asp Ala 50 55 60 Asn Leu Ile Pro Pro Val Pro Asp Asp Lys Phe Gln Asp Leu Val Asp 65 70 75 80 Ala Val Arg Ala Glu Lys Gly Phe Leu Leu Leu Ala Ser Leu Arg Gln 85 90 95 Met Lys Lys Thr Arg Gly Thr Leu Leu Ala Leu Glu Arg Lys Asp His 100 105 110 Ser Gly Gln Val Phe Ser Val Val Ser Asn Gly Lys Ala Gly Thr Leu 115 120 125 Asp Leu Ser Leu Thr Val Gln Gly Lys Gln His Val Val Ser Val Glu 130 135 140 Glu Ala Leu Leu Ala Thr Gly Gln Trp Lys Ser Ile Thr Leu Phe Val 145 150 155 160 Gln Glu Asp Arg Ala Gln Leu Tyr Ile Asp Cys Glu Lys Met Glu Asn 165 170 175 Ala Glu Leu Asp Val Pro Ile Gln Ser Val Phe Thr Arg Asp Leu Ala 180 185 190 Ser Ile Ala Arg Leu Arg Ile Ala Lys Gly Gly Val Asn Asp Asn Phe 195 200 205 Gln Gly Val Leu Gln Asn Val Arg Phe Val Phe Gly Thr Thr Pro Glu 210 215 220 Asp Ile Leu Arg Asn Lys Gly Cys Ser Ser Ser Thr Ser Val Leu Leu 225 230 235 240 Thr Leu Asp Asn Asn Val Val Asn Gly Ser Ser Pro Ala Ile Arg Thr 245 250 255 Asn Tyr Ile Gly His Lys Thr Lys Asp Leu Gln Ala Ile Cys Gly Ile 260 265 270 Ser Cys Asp Glu Leu Ser Ser Met Val Leu Glu Leu Arg Gly Leu Arg 275 280 285 Thr Ile Val Thr Thr Leu Gln Asp Ser Ile Arg Lys Val Thr Glu Glu 290 295 300 Asn Lys Glu Leu Ala Asn Glu Leu Arg Arg Pro Pro Leu Cys Tyr His 305 310 315 320 Asn Gly Val Gln Tyr Arg Asn Asn Glu Glu Trp Thr Val Asp Ser Cys 325 330 335 Thr Glu Cys His Cys Gln Asn Ser Val Thr Ile Cys Lys Lys Val Ser 340 345 350 Cys Pro Ile Met Pro Cys Ser Asn Ala Thr Val Pro Asp Gly Glu Cys 355 360 365 Cys Pro Arg Cys Trp Pro Ser Asp Ser Ala Asp Asp Gly Trp Ser Pro 370 375 380 Trp Ser Glu Trp Thr Ser Cys Ser Thr Ser Cys Gly Asn Gly Ile Gln 385 390 395 400 Gln Arg Gly Arg Ser Cys Asp Ser Leu Asn Asn Arg Cys Glu Gly Ser 405 410 415 Ser Val Gln Thr Arg Thr Cys His Ile Gln Glu Cys Asp Lys Arg Phe 420 425 430 Lys Gln Asp Gly Gly Trp Ser His Trp Ser Pro Trp Ser Ser Cys Ser 435 440 445 Val Thr Cys Gly Asp Gly Val Ile Thr Arg Ile Arg Leu Cys Asn Ser 450 455 460 Pro Ser Pro Gln Met Asn Gly Lys Pro Cys Glu Gly Glu Ala Arg Glu 465 470 475 480 Thr Lys Ala Cys Lys Lys Asp Ala Cys Pro Ile Asn Gly Gly Trp Gly 485 490 495 Pro Trp Ser Pro Trp Asp Ile Cys Ser Val Thr Cys Gly Gly Gly Val 500 505 510 Gln Lys Arg Ser Arg Leu Cys Asn Asn Pro Thr Pro Gln Phe Gly Gly 515 520 525 Lys Asp Cys Val Gly Asp Val Thr Glu Asn Gln Ile Cys Asn Lys Gln 530 535 540 Asp Cys Pro Ile Asp Gly Cys Leu Ser Asn Pro Cys Phe Ala Gly Val 545 550 555 560 Lys Cys Thr Ser Tyr Pro Asp Gly Ser Trp Lys Cys Gly Ala Cys Pro 565 570 575 Pro Gly Tyr Ser Gly Asn Gly Ile Gln Cys Thr Asp Val Asp Glu Cys 580 585 590 Lys Glu Val Pro Asp Ala Cys Phe Asn His Asn Gly Glu His Arg Cys 595 600 605 Glu Asn Thr Asp Pro Gly Tyr Asn Cys Leu Pro Cys Pro Pro Arg Phe 610 615 620 Thr Gly Ser Gln Pro Phe Gly Gln Gly Val Glu His Ala Thr Ala Asn 625 630 635 640 Lys Gln Val Cys Lys Pro Arg Asn Pro Cys Thr Asp Gly Thr His Asp 645 650 655 Cys Asn Lys Asn Ala Lys Cys Asn Tyr Leu Gly His Tyr Ser Asp Pro 660 665 670 Met Tyr Arg Cys Glu Cys Lys Pro Gly Tyr Ala Gly Asn Gly Ile Ile 675 680 685 Cys Gly Glu Asp Thr Asp Leu Asp Gly Trp Pro Asn Glu Asn Leu Val 690 695 700 Cys Val Ala Asn Ala Thr Tyr His Cys Lys Lys Asp Asn Cys Pro Asn 705 710 715 720 Leu Pro Asn Ser Gly Gln Glu Asp Tyr Asp Lys Asp Gly Ile Gly Asp 725 730 735 Ala Cys Asp Asp Asp Asp Asp Asn Asp Lys Ile Pro Asp Asp Arg Asp 740 745 750 Asn Cys Pro Phe His Tyr Asn Pro Ala Gln Tyr Asp Tyr Asp Arg Asp 755 760 765 Asp Val Gly Asp Arg Cys Asp Asn Cys Pro Tyr Asn His Asn Pro Asp 770 775 780 Gln Ala Asp Thr Asp Asn Asn Gly Glu Gly Asp Ala Cys Ala Ala Asp 785 790 795 800 Ile Asp Gly Asp Gly Ile Leu Asn Glu Arg Asp Asn Cys Gln Tyr Val 805 810 815 Tyr Asn Val Asp Gln Arg Asp Thr Asp Met Asp Gly Val Gly Asp Gln 820 825 830 Cys Asp Asn Cys Pro Leu Glu His Asn Pro Asp Gln Leu Asp Ser Asp 835 840 845 Ser Asp Arg Ile Gly Asp Thr Cys Asp Asn Asn Gln Asp Ile Asp Glu 850 855 860 Asp Gly His Gln Asn Asn Leu Asp Asn Cys Pro Tyr Val Pro Asn Ala 865 870 875 880 Asn Gln Ala Asp His Asp Lys Asp Gly Lys Gly Asp Ala Cys Asp His 885 890 895 Asp Asp Asp Asn Asp Gly Ile Pro Asp Asp Lys Asp Asn Cys Arg Leu 900 905 910 Val Pro Asn Pro Asp Gln Lys Asp Ser Asp Gly Asp Gly Arg Gly Asp 915 920 925 Ala Cys Lys Asp Asp Phe Asp His Asp Ser Val Pro Asp Ile Asp Asp 930 935 940 Ile Cys Pro Glu Asn Val Asp Ile Ser Glu Thr Asp Phe Arg Arg Phe 945 950 955 960 Gln Met Ile Pro Leu Asp Pro Lys Gly Thr Ser Gln Asn Asp Pro Asn 965 970 975 Trp Val Val Arg His Gln Gly Lys Glu Leu Val Gln Thr Val Asn Cys 980 985 990 Asp Pro Gly Leu Ala Val Gly Tyr Asp Glu Phe Asn Ala Val Asp Phe 995 1000 1005 Ser Gly Thr Phe Phe Ile Asn Thr Glu Arg Asp Asp Asp Tyr Ala Gly 1010 1015 1020 Phe Val Phe Gly Tyr Gln Ser Ser Ser Arg Phe Tyr Val Val Met Trp 1025 1030 1035 1040 Lys Gln Val Thr Gln Ser Tyr Trp Asp Thr Asn Pro Thr Arg Ala Gln 1045 1050 1055 Gly Tyr Ser Gly Leu Ser Val Lys Val Val Asn Ser Thr Thr Gly Pro 1060 1065 1070 Gly Glu His Leu Arg Asn Ala Leu Trp His Thr Gly Asn Thr Pro Gly 1075 1080 1085 Gln Val Arg Thr Leu Trp His Asp Pro Arg His Ile Gly Trp Lys Asp 1090 1095 1100 Phe Thr Ala Tyr Arg Trp Arg Leu Ser His Arg Pro Lys Thr Gly Phe 1105 1110 1115 1120 Ile Arg Val Val Met Tyr Glu Gly Lys Lys Ile Met Ala Asp Ser Gly 1125 1130 1135 Pro Ile Tyr Asp Lys Thr Tyr Ala Gly Gly Arg Leu Gly Leu Phe Val 1140 1145 1150 Phe Ser Gln Glu Met Val Phe Phe Ser Asp Leu Lys Tyr Glu Cys Arg 1155 1160 1165 Asp Pro 1170 <210> SEQ ID NO 81 <211> LENGTH: 1516 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 81 Met Ala Pro Tyr Pro Cys Gly Cys His Ile Leu Leu Leu Leu Phe Cys 1 5 10 15 Cys Leu Ala Ala Ala Arg Ala Asn Leu Leu Asn Leu Asn Trp Leu Trp 20 25 30 Phe Asn Asn Glu Asp Thr Ser His Ala Ala Thr Thr Ile Pro Glu Pro 35 40 45 Gln Gly Pro Leu Pro Val Gln Pro Thr Ala Asp Thr Thr Thr His Val 50 55 60 Thr Pro Arg Asn Gly Ser Thr Glu Pro Ala Thr Ala Pro Gly Ser Pro 65 70 75 80 Glu Pro Pro Ser Glu Leu Leu Glu Asp Gly Gln Asp Thr Pro Thr Ser 85 90 95 Ala Glu Ser Pro Asp Ala Pro Glu Glu Asn Ile Ala Gly Val Gly Ala 100 105 110 Glu Ile Leu Asn Val Ala Lys Gly Ile Arg Ser Phe Val Gln Leu Trp 115 120 125 Asn Asp Thr Val Pro Thr Glu Ser Leu Ala Arg Ala Glu Thr Leu Val 130 135 140 Leu Glu Thr Pro Val Gly Pro Leu Ala Leu Ala Gly Pro Ser Ser Thr 145 150 155 160 Pro Gln Glu Asn Gly Thr Thr Leu Trp Pro Ser Arg Gly Ile Pro Ser 165 170 175 Ser Pro Gly Ala His Thr Thr Glu Ala Gly Thr Leu Pro Ala Pro Thr 180 185 190 Pro Ser Pro Pro Ser Leu Gly Arg Pro Trp Ala Pro Leu Thr Gly Pro 195 200 205 Ser Val Pro Pro Pro Ser Ser Glu Arg Ile Ser Glu Glu Val Gly Leu 210 215 220 Leu Gln Leu Leu Gly Asp Pro Pro Pro Gln Gln Val Thr Gln Thr Asp 225 230 235 240 Asp Pro Asp Val Gly Leu Ala Tyr Val Phe Gly Pro Asp Ala Asn Ser 245 250 255 Gly Gln Val Ala Arg Tyr His Phe Pro Ser Leu Phe Phe Arg Asp Phe 260 265 270 Ser Leu Leu Phe His Ile Arg Pro Ala Thr Glu Gly Pro Gly Val Leu 275 280 285 Phe Ala Ile Thr Asp Ser Ala Gln Ala Met Val Leu Leu Gly Val Lys 290 295 300 Leu Ser Gly Val Gln Asp Gly His Gln Asp Ile Ser Leu Leu Tyr Thr 305 310 315 320 Glu Pro Gly Ala Gly Gln Thr His Thr Ala Ala Ser Phe Arg Leu Pro 325 330 335 Ala Phe Val Gly Gln Trp Thr His Leu Ala Leu Ser Val Ala Gly Gly 340 345 350 Phe Val Ala Leu Tyr Val Asp Cys Glu Glu Phe Gln Arg Met Pro Leu 355 360 365 Ala Arg Ser Ser Arg Gly Leu Glu Leu Glu Pro Gly Ala Gly Leu Phe 370 375 380 Val Ala Gln Ala Gly Gly Ala Asp Pro Asp Lys Phe Gln Gly Val Ile 385 390 395 400 Ala Glu Leu Lys Val Arg Arg Asp Pro Gln Val Ser Pro Met His Cys 405 410 415 Leu Asp Glu Glu Gly Asp Asp Ser Asp Gly Ala Ser Gly Asp Ser Gly 420 425 430 Ser Gly Leu Gly Asp Ala Arg Glu Leu Leu Arg Glu Glu Thr Gly Ala 435 440 445 Ala Leu Lys Pro Arg Leu Pro Ala Pro Pro Pro Val Thr Thr Pro Pro 450 455 460 Leu Ala Gly Gly Ser Ser Thr Glu Asp Ser Arg Ser Glu Glu Val Glu 465 470 475 480 Glu Gln Thr Thr Val Ala Ser Leu Gly Ala Gln Thr Leu Pro Gly Ser 485 490 495 Asp Ser Val Ser Thr Trp Asp Gly Ser Val Arg Thr Pro Gly Gly Arg 500 505 510 Val Lys Glu Gly Gly Leu Lys Gly Gln Lys Gly Glu Pro Gly Val Pro 515 520 525 Gly Pro Pro Gly Arg Ala Gly Pro Pro Gly Ser Pro Cys Leu Pro Gly 530 535 540 Pro Pro Gly Leu Pro Cys Pro Val Ser Pro Leu Gly Pro Ala Gly Pro 545 550 555 560 Ala Leu Gln Thr Val Pro Gly Pro Gln Gly Pro Pro Gly Pro Pro Gly 565 570 575 Arg Asp Gly Thr Pro Gly Arg Asp Gly Glu Pro Gly Asp Pro Gly Glu 580 585 590 Asp Gly Lys Pro Gly Asp Thr Gly Pro Gln Gly Phe Pro Gly Thr Pro 595 600 605 Gly Asp Val Gly Pro Lys Gly Asp Lys Gly Asp Pro Gly Val Gly Glu 610 615 620 Arg Gly Pro Pro Gly Pro Gln Gly Pro Pro Gly Pro Pro Gly Pro Ser 625 630 635 640 Phe Arg His Asp Lys Leu Thr Phe Ile Asp Met Glu Gly Ser Gly Phe 645 650 655 Gly Gly Asp Leu Glu Ala Leu Arg Gly Pro Arg Gly Phe Pro Gly Pro 660 665 670 Pro Gly Pro Pro Gly Val Pro Gly Leu Pro Gly Glu Pro Gly Arg Phe 675 680 685 Gly Val Asn Ser Ser Asp Val Pro Gly Pro Ala Gly Leu Pro Gly Val 690 695 700 Pro Gly Arg Glu Gly Pro Pro Gly Phe Pro Gly Leu Pro Gly Pro Pro 705 710 715 720 Gly Pro Pro Gly Arg Glu Gly Pro Pro Gly Arg Thr Gly Gln Lys Gly 725 730 735 Ser Leu Gly Glu Ala Gly Ala Pro Gly His Lys Gly Ser Lys Gly Ala 740 745 750 Pro Gly Pro Ala Gly Ala Arg Gly Glu Ser Gly Leu Ala Gly Ala Pro 755 760 765 Gly Pro Ala Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly 770 775 780 Pro Gly Leu Pro Ala Gly Phe Asp Asp Met Glu Gly Ser Gly Gly Pro 785 790 795 800 Phe Trp Ser Thr Ala Arg Ser Ala Asp Gly Pro Gln Gly Pro Pro Gly 805 810 815 Leu Pro Gly Leu Lys Gly Asp Pro Gly Val Pro Gly Leu Pro Gly Ala 820 825 830 Lys Gly Glu Val Gly Ala Asp Gly Val Pro Gly Phe Pro Gly Leu Pro 835 840 845 Gly Arg Glu Gly Ile Ala Gly Pro Gln Gly Pro Lys Gly Asp Arg Gly 850 855 860 Ser Arg Gly Glu Lys Gly Asp Pro Gly Lys Asp Gly Val Gly Gln Pro 865 870 875 880 Gly Leu Pro Gly Pro Pro Gly Pro Pro Gly Pro Val Val Tyr Val Ser 885 890 895 Glu Gln Asp Gly Ser Val Leu Ser Val Pro Gly Pro Glu Gly Arg Pro 900 905 910 Gly Phe Ala Gly Phe Pro Gly Pro Ala Gly Pro Lys Gly Asn Leu Gly 915 920 925 Ser Lys Gly Glu Arg Gly Ser Pro Gly Pro Lys Gly Glu Lys Gly Glu 930 935 940 Pro Gly Ser Ile Phe Ser Pro Asp Gly Gly Ala Leu Gly Pro Ala Gln 945 950 955 960 Lys Gly Ala Lys Gly Glu Pro Gly Phe Arg Gly Pro Pro Gly Pro Tyr 965 970 975 Gly Arg Pro Gly Tyr Lys Gly Glu Ile Gly Phe Pro Gly Arg Pro Gly 980 985 990 Arg Pro Gly Met Asn Gly Leu Lys Gly Glu Lys Gly Glu Pro Gly Asp 995 1000 1005 Ala Ser Leu Gly Phe Gly Met Arg Gly Met Pro Gly Pro Pro Gly Pro 1010 1015 1020 Pro Gly Pro Pro Gly Pro Pro Gly Thr Pro Val Tyr Asp Ser Asn Val 1025 1030 1035 1040 Phe Ala Glu Ser Ser Arg Pro Gly Pro Pro Gly Leu Pro Gly Asn Gln 1045 1050 1055 Gly Pro Pro Gly Pro Lys Gly Ala Lys Gly Glu Val Gly Pro Pro Gly 1060 1065 1070 Pro Pro Gly Gln Phe Pro Phe Asp Phe Leu Gln Leu Glu Ala Glu Met 1075 1080 1085 Lys Gly Glu Lys Gly Asp Arg Gly Asp Ala Gly Gln Lys Gly Glu Arg 1090 1095 1100 Gly Glu Pro Gly Gly Gly Gly Phe Phe Gly Ser Ser Leu Pro Gly Pro 1105 1110 1115 1120 Pro Gly Pro Pro Gly Pro Arg Gly Tyr Pro Gly Ile Pro Gly Pro Lys 1125 1130 1135 Gly Glu Ser Ile Arg Gly Gln Pro Gly Pro Pro Gly Pro Gln Gly Pro 1140 1145 1150 Pro Gly Ile Gly Tyr Glu Gly Arg Gln Gly Pro Pro Gly Pro Pro Gly 1155 1160 1165 Pro Pro Gly Pro Pro Ser Phe Pro Gly Pro His Arg Gln Thr Ile Ser 1170 1175 1180 Val Pro Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly Thr 1185 1190 1195 1200 Met Gly Ala Ser Ser Gly Val Arg Leu Trp Ala Thr Arg Gln Ala Met 1205 1210 1215 Leu Gly Gln Val His Glu Val Pro Glu Gly Trp Leu Ile Phe Val Ala 1220 1225 1230 Glu Gln Glu Glu Leu Tyr Val Arg Val Gln Asn Gly Phe Arg Lys Val 1235 1240 1245 Gln Leu Glu Ala Arg Thr Pro Leu Pro Arg Gly Thr Asp Asn Glu Val 1250 1255 1260 Ala Ala Leu Gln Pro Pro Val Val Gln Leu His Asp Ser Asn Pro Tyr 1265 1270 1275 1280 Pro Arg Arg Glu His Pro His Pro Thr Ala Arg Pro Trp Arg Ala Asp 1285 1290 1295 Asp Ile Leu Ala Ser Pro Pro Arg Leu Pro Glu Pro Gln Pro Tyr Pro 1300 1305 1310 Gly Ala Pro His His Ser Ser Tyr Val His Leu Arg Pro Ala Arg Pro 1315 1320 1325 Thr Ser Pro Pro Ala His Ser His Arg Asp Phe Gln Pro Val Leu His 1330 1335 1340 Leu Val Ala Leu Asn Ser Pro Leu Ser Gly Gly Met Arg Gly Ile Arg 1345 1350 1355 1360 Gly Ala Asp Phe Gln Cys Phe Gln Gln Ala Arg Ala Val Gly Leu Ala 1365 1370 1375 Gly Thr Phe Arg Ala Phe Leu Ser Ser Arg Leu Gln Asp Leu Tyr Ser 1380 1385 1390 Ile Val Arg Arg Ala Asp Arg Ala Ala Val Pro Ile Val Asn Leu Lys 1395 1400 1405 Asp Glu Leu Leu Phe Pro Ser Trp Glu Ala Leu Phe Ser Gly Ser Glu 1410 1415 1420 Gly Pro Leu Lys Pro Gly Ala Arg Ile Phe Ser Phe Asp Gly Lys Asp 1425 1430 1435 1440 Val Leu Arg His Pro Thr Trp Pro Gln Lys Ser Val Trp His Gly Ser 1445 1450 1455 Asp Pro Asn Gly Arg Arg Leu Thr Glu Ser Tyr Cys Glu Thr Trp Arg 1460 1465 1470 Thr Glu Ala Pro Ser Ala Thr Gly Gln Ala Ser Ser Leu Leu Gly Gly 1475 1480 1485 Arg Leu Leu Gly Gln Ser Ala Ala Ser Cys His His Ala Tyr Ile Val 1490 1495 1500 Leu Cys Ile Glu Asn Ser Phe Met Thr Ala Ser Lys 1505 1510 1515 <210> SEQ ID NO 82 <211> LENGTH: 1336 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 82 Met Ala Pro Arg Cys Pro Trp Pro Trp Pro Arg Arg Arg Arg Leu Leu 1 5 10 15 Asp Val Leu Ala Pro Leu Val Leu Leu Leu Gly Val Arg Ala Ala Ser 20 25 30 Ala Glu Pro Glu Arg Ile Ser Glu Glu Val Gly Leu Leu Gln Leu Leu 35 40 45 Gly Asp Pro Pro Pro Gln Gln Val Thr Gln Thr Asp Asp Pro Asp Val 50 55 60 Gly Leu Ala Tyr Val Phe Gly Pro Asp Ala Asn Ser Gly Gln Val Ala 65 70 75 80 Arg Tyr His Phe Pro Ser Leu Phe Phe Arg Asp Phe Ser Leu Leu Phe 85 90 95 His Ile Arg Pro Ala Thr Glu Gly Pro Gly Val Leu Phe Ala Ile Thr 100 105 110 Asp Ser Ala Gln Ala Met Val Leu Leu Gly Val Lys Leu Ser Gly Val 115 120 125 Gln Asp Gly His Gln Asp Ile Ser Leu Leu Tyr Thr Glu Pro Gly Ala 130 135 140 Gly Gln Thr His Thr Ala Ala Ser Phe Arg Leu Pro Ala Phe Val Gly 145 150 155 160 Gln Trp Thr His Leu Ala Leu Ser Val Ala Gly Gly Phe Val Ala Leu 165 170 175 Tyr Val Asp Cys Glu Glu Phe Gln Arg Met Pro Leu Ala Arg Ser Ser 180 185 190 Arg Gly Leu Glu Leu Glu Pro Gly Ala Gly Leu Phe Val Ala Gln Ala 195 200 205 Gly Gly Ala Asp Pro Asp Lys Phe Gln Gly Val Ile Ala Glu Leu Lys 210 215 220 Val Arg Arg Asp Pro Gln Val Ser Pro Met His Cys Leu Asp Glu Glu 225 230 235 240 Gly Asp Asp Ser Asp Gly Ala Ser Gly Asp Ser Gly Ser Gly Leu Gly 245 250 255 Asp Ala Arg Glu Leu Leu Arg Glu Glu Thr Gly Ala Ala Leu Lys Pro 260 265 270 Arg Leu Pro Ala Pro Pro Pro Val Thr Thr Pro Pro Leu Ala Gly Gly 275 280 285 Ser Ser Thr Glu Asp Ser Arg Ser Glu Glu Val Glu Glu Gln Thr Thr 290 295 300 Val Ala Ser Leu Gly Ala Gln Thr Leu Pro Gly Ser Asp Ser Val Ser 305 310 315 320 Thr Trp Asp Gly Ser Val Arg Thr Pro Gly Gly Arg Val Lys Glu Gly 325 330 335 Gly Leu Lys Gly Gln Lys Gly Glu Pro Gly Val Pro Gly Pro Pro Gly 340 345 350 Arg Ala Gly Pro Pro Gly Ser Pro Cys Leu Pro Gly Pro Pro Gly Leu 355 360 365 Pro Cys Pro Val Ser Pro Leu Gly Pro Ala Gly Pro Ala Leu Gln Thr 370 375 380 Val Pro Gly Pro Gln Gly Pro Pro Gly Pro Pro Gly Arg Asp Gly Thr 385 390 395 400 Pro Gly Arg Asp Gly Glu Pro Gly Asp Pro Gly Glu Asp Gly Lys Pro 405 410 415 Gly Asp Thr Gly Pro Gln Gly Phe Pro Gly Thr Pro Gly Asp Val Gly 420 425 430 Pro Lys Gly Asp Lys Gly Asp Pro Gly Val Gly Glu Arg Gly Pro Pro 435 440 445 Gly Pro Gln Gly Pro Pro Gly Pro Pro Gly Pro Ser Phe Arg His Asp 450 455 460 Lys Leu Thr Phe Ile Asp Met Glu Gly Ser Gly Phe Gly Gly Asp Leu 465 470 475 480 Glu Ala Leu Arg Gly Pro Arg Gly Phe Pro Gly Pro Pro Gly Pro Pro 485 490 495 Gly Val Pro Gly Leu Pro Gly Glu Pro Gly Arg Phe Gly Val Asn Ser 500 505 510 Ser Asp Val Pro Gly Pro Ala Gly Leu Pro Gly Val Pro Gly Arg Glu 515 520 525 Gly Pro Pro Gly Phe Pro Gly Leu Pro Gly Pro Pro Gly Pro Pro Gly 530 535 540 Arg Glu Gly Pro Pro Gly Arg Thr Gly Gln Lys Gly Ser Leu Gly Glu 545 550 555 560 Ala Gly Ala Pro Gly His Lys Gly Ser Lys Gly Ala Pro Gly Pro Ala 565 570 575 Gly Ala Arg Gly Glu Ser Gly Leu Ala Gly Ala Pro Gly Pro Ala Gly 580 585 590 Pro Pro Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly Pro Gly Leu Pro 595 600 605 Ala Gly Phe Asp Asp Met Glu Gly Ser Gly Gly Pro Phe Trp Ser Thr 610 615 620 Ala Arg Ser Ala Asp Gly Pro Gln Gly Pro Pro Gly Leu Pro Gly Leu 625 630 635 640 Lys Gly Asp Pro Gly Val Pro Gly Leu Pro Gly Ala Lys Gly Glu Val 645 650 655 Gly Ala Asp Gly Val Pro Gly Phe Pro Gly Leu Pro Gly Arg Glu Gly 660 665 670 Ile Ala Gly Pro Gln Gly Pro Lys Gly Asp Arg Gly Ser Arg Gly Glu 675 680 685 Lys Gly Asp Pro Gly Lys Asp Gly Val Gly Gln Pro Gly Leu Pro Gly 690 695 700 Pro Pro Gly Pro Pro Gly Pro Val Val Tyr Val Ser Glu Gln Asp Gly 705 710 715 720 Ser Val Leu Ser Val Pro Gly Pro Glu Gly Arg Pro Gly Phe Ala Gly 725 730 735 Phe Pro Gly Pro Ala Gly Pro Lys Gly Asn Leu Gly Ser Lys Gly Glu 740 745 750 Arg Gly Ser Pro Gly Pro Lys Gly Glu Lys Gly Glu Pro Gly Ser Ile 755 760 765 Phe Ser Pro Asp Gly Gly Ala Leu Gly Pro Ala Gln Lys Gly Ala Lys 770 775 780 Gly Glu Pro Gly Phe Arg Gly Pro Pro Gly Pro Tyr Gly Arg Pro Gly 785 790 795 800 Tyr Lys Gly Glu Ile Gly Phe Pro Gly Arg Pro Gly Arg Pro Gly Met 805 810 815 Asn Gly Leu Lys Gly Glu Lys Gly Glu Pro Gly Asp Ala Ser Leu Gly 820 825 830 Phe Gly Met Arg Gly Met Pro Gly Pro Pro Gly Pro Pro Gly Pro Pro 835 840 845 Gly Pro Pro Gly Thr Pro Val Tyr Asp Ser Asn Val Phe Ala Glu Ser 850 855 860 Ser Arg Pro Gly Pro Pro Gly Leu Pro Gly Asn Gln Gly Pro Pro Gly 865 870 875 880 Pro Lys Gly Ala Lys Gly Glu Val Gly Pro Pro Gly Pro Pro Gly Gln 885 890 895 Phe Pro Phe Asp Phe Leu Gln Leu Glu Ala Glu Met Lys Gly Glu Lys 900 905 910 Gly Asp Arg Gly Asp Ala Gly Gln Lys Gly Glu Arg Gly Glu Pro Gly 915 920 925 Gly Gly Gly Phe Phe Gly Ser Ser Leu Pro Gly Pro Pro Gly Pro Pro 930 935 940 Gly Pro Arg Gly Tyr Pro Gly Ile Pro Gly Pro Lys Gly Glu Ser Ile 945 950 955 960 Arg Gly Gln Pro Gly Pro Pro Gly Pro Gln Gly Pro Pro Gly Ile Gly 965 970 975 Tyr Glu Gly Arg Gln Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly Pro 980 985 990 Pro Ser Phe Pro Gly Pro His Arg Gln Thr Ile Ser Val Pro Gly Pro 995 1000 1005 Pro Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly Thr Met Gly Ala Ser 1010 1015 1020 Ser Gly Val Arg Leu Trp Ala Thr Arg Gln Ala Met Leu Gly Gln Val 1025 1030 1035 1040 His Glu Val Pro Glu Gly Trp Leu Ile Phe Val Ala Glu Gln Glu Glu 1045 1050 1055 Leu Tyr Val Arg Val Gln Asn Gly Phe Arg Lys Val Gln Leu Glu Ala 1060 1065 1070 Arg Thr Pro Leu Pro Arg Gly Thr Asp Asn Glu Val Ala Ala Leu Gln 1075 1080 1085 Pro Pro Val Val Gln Leu His Asp Ser Asn Pro Tyr Pro Arg Arg Glu 1090 1095 1100 His Pro His Pro Thr Ala Arg Pro Trp Arg Ala Asp Asp Ile Leu Ala 1105 1110 1115 1120 Ser Pro Pro Arg Leu Pro Glu Pro Gln Pro Tyr Pro Gly Ala Pro His 1125 1130 1135 His Ser Ser Tyr Val His Leu Arg Pro Ala Arg Pro Thr Ser Pro Pro 1140 1145 1150 Ala His Ser His Arg Asp Phe Gln Pro Val Leu His Leu Val Ala Leu 1155 1160 1165 Asn Ser Pro Leu Ser Gly Gly Met Arg Gly Ile Arg Gly Ala Asp Phe 1170 1175 1180 Gln Cys Phe Gln Gln Ala Arg Ala Val Gly Leu Ala Gly Thr Phe Arg 1185 1190 1195 1200 Ala Phe Leu Ser Ser Arg Leu Gln Asp Leu Tyr Ser Ile Val Arg Arg 1205 1210 1215 Ala Asp Arg Ala Ala Val Pro Ile Val Asn Leu Lys Asp Glu Leu Leu 1220 1225 1230 Phe Pro Ser Trp Glu Ala Leu Phe Ser Gly Ser Glu Gly Pro Leu Lys 1235 1240 1245 Pro Gly Ala Arg Ile Phe Ser Phe Asp Gly Lys Asp Val Leu Arg His 1250 1255 1260 Pro Thr Trp Pro Gln Lys Ser Val Trp His Gly Ser Asp Pro Asn Gly 1265 1270 1275 1280 Arg Arg Leu Thr Glu Ser Tyr Cys Glu Thr Trp Arg Thr Glu Ala Pro 1285 1290 1295 Ser Ala Thr Gly Gln Ala Ser Ser Leu Leu Gly Gly Arg Leu Leu Gly 1300 1305 1310 Gln Ser Ala Ala Ser Cys His His Ala Tyr Ile Val Leu Cys Ile Glu 1315 1320 1325 Asn Ser Phe Met Thr Ala Ser Lys 1330 1335 <210> SEQ ID NO 83 <211> LENGTH: 1670 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 83 Met Ser Ala Arg Thr Ala Pro Arg Pro Gln Val Leu Leu Leu Pro Leu 1 5 10 15 Leu Leu Val Leu Leu Ala Ala Ala Pro Ala Ala Ser Lys Gly Cys Val 20 25 30 Cys Lys Asp Lys Gly Gln Cys Phe Cys Asp Gly Ala Lys Gly Glu Lys 35 40 45 Gly Glu Lys Gly Phe Pro Gly Pro Pro Gly Ser Pro Gly Gln Lys Gly 50 55 60 Phe Thr Gly Pro Glu Gly Leu Pro Gly Pro Gln Gly Pro Lys Gly Phe 65 70 75 80 Pro Gly Leu Pro Gly Leu Thr Gly Ser Lys Gly Val Arg Gly Ile Ser 85 90 95 Gly Leu Pro Gly Phe Ser Gly Ser Pro Gly Leu Pro Gly Thr Pro Gly 100 105 110 Asn Thr Gly Pro Tyr Gly Leu Val Gly Val Pro Gly Cys Ser Gly Ser 115 120 125 Lys Gly Glu Gln Gly Phe Pro Gly Leu Pro Gly Thr Leu Gly Tyr Pro 130 135 140 Gly Ile Pro Gly Ala Ala Gly Leu Lys Gly Gln Lys Gly Ala Pro Ala 145 150 155 160 Lys Glu Glu Asp Ile Glu Leu Asp Ala Lys Gly Asp Pro Gly Leu Pro 165 170 175 Gly Ala Pro Gly Pro Gln Gly Leu Pro Gly Pro Pro Gly Phe Pro Gly 180 185 190 Pro Val Gly Pro Pro Gly Pro Pro Gly Phe Phe Gly Phe Pro Gly Ala 195 200 205 Met Gly Pro Arg Gly Pro Lys Gly His Met Gly Glu Arg Val Ile Gly 210 215 220 His Lys Gly Glu Arg Gly Val Lys Gly Leu Thr Gly Pro Pro Gly Pro 225 230 235 240 Pro Gly Thr Val Ile Val Thr Leu Thr Gly Pro Asp Asn Arg Thr Asp 245 250 255 Leu Lys Gly Glu Lys Gly Asp Lys Gly Ala Met Gly Glu Pro Gly Pro 260 265 270 Pro Gly Pro Ser Gly Leu Pro Gly Glu Ser Tyr Gly Ser Glu Lys Gly 275 280 285 Ala Pro Gly Asp Pro Gly Leu Gln Gly Lys Pro Gly Lys Asp Gly Val 290 295 300 Pro Gly Phe Pro Gly Ser Glu Gly Val Lys Gly Asn Arg Gly Phe Pro 305 310 315 320 Gly Leu Met Gly Glu Asp Gly Ile Lys Gly Gln Lys Gly Asp Ile Gly 325 330 335 Pro Pro Gly Phe Arg Gly Pro Thr Glu Tyr Tyr Asp Thr Tyr Gln Glu 340 345 350 Lys Gly Asp Glu Gly Thr Pro Gly Pro Pro Gly Pro Arg Gly Ala Arg 355 360 365 Gly Pro Gln Gly Pro Ser Gly Pro Pro Gly Val Pro Gly Ser Pro Gly 370 375 380 Ser Ser Arg Pro Gly Leu Arg Gly Ala Pro Gly Trp Pro Gly Leu Lys 385 390 395 400 Gly Ser Lys Gly Glu Arg Gly Arg Pro Gly Lys Asp Ala Met Gly Thr 405 410 415 Pro Gly Ser Pro Gly Cys Ala Gly Ser Pro Gly Leu Pro Gly Ser Pro 420 425 430 Gly Pro Pro Gly Pro Pro Gly Asp Ile Val Phe Arg Lys Gly Pro Pro 435 440 445 Gly Asp His Gly Leu Pro Gly Tyr Leu Gly Ser Pro Gly Ile Pro Gly 450 455 460 Val Asp Gly Pro Lys Gly Glu Pro Gly Leu Leu Cys Thr Gln Cys Pro 465 470 475 480 Tyr Ile Pro Gly Pro Pro Gly Leu Pro Gly Leu Pro Gly Leu His Gly 485 490 495 Val Lys Gly Ile Pro Gly Arg Gln Gly Ala Ala Gly Leu Lys Gly Ser 500 505 510 Pro Gly Ser Pro Gly Asn Thr Gly Leu Pro Gly Phe Pro Gly Phe Pro 515 520 525 Gly Ala Gln Gly Asp Pro Gly Leu Lys Gly Glu Lys Gly Glu Thr Leu 530 535 540 Gln Pro Glu Gly Gln Val Gly Val Pro Gly Asp Pro Gly Leu Arg Gly 545 550 555 560 Gln Pro Gly Arg Lys Gly Leu Asp Gly Ile Pro Gly Thr Pro Gly Val 565 570 575 Lys Gly Leu Pro Gly Pro Lys Gly Glu Leu Ala Leu Ser Gly Glu Lys 580 585 590 Gly Asp Gln Gly Pro Pro Gly Asp Pro Gly Ser Pro Gly Ser Pro Gly 595 600 605 Pro Ala Gly Pro Ala Gly Pro Pro Gly Tyr Gly Pro Gln Gly Glu Pro 610 615 620 Gly Leu Gln Gly Thr Gln Gly Val Pro Gly Ala Pro Gly Pro Pro Gly 625 630 635 640 Glu Ala Gly Pro Arg Gly Glu Leu Ser Val Ser Thr Pro Val Pro Gly 645 650 655 Pro Pro Gly Pro Pro Gly Pro Pro Gly His Pro Gly Pro Gln Gly Pro 660 665 670 Pro Gly Ile Pro Gly Ser Leu Gly Lys Cys Gly Asp Pro Gly Leu Pro 675 680 685 Gly Pro Asp Gly Glu Pro Gly Ile Pro Gly Ile Gly Phe Pro Gly Pro 690 695 700 Pro Gly Pro Lys Gly Asp Gln Gly Phe Pro Gly Thr Lys Gly Ser Leu 705 710 715 720 Gly Cys Pro Gly Lys Met Gly Glu Pro Gly Leu Pro Gly Lys Pro Gly 725 730 735 Leu Pro Gly Ala Lys Gly Glu Pro Ala Val Ala Met Pro Gly Gly Pro 740 745 750 Gly Thr Pro Gly Phe Pro Gly Glu Arg Gly Asn Ser Gly Glu His Gly 755 760 765 Glu Ile Gly Leu Pro Gly Leu Pro Gly Leu Pro Gly Thr Pro Gly Asn 770 775 780 Glu Gly Leu Asp Gly Pro Arg Gly Asp Pro Gly Gln Pro Gly Pro Pro 785 790 795 800 Gly Glu Gln Gly Pro Pro Gly Arg Cys Ile Glu Gly Pro Arg Gly Ala 805 810 815 Gln Gly Leu Pro Gly Leu Asn Gly Leu Lys Gly Gln Gln Gly Arg Arg 820 825 830 Gly Lys Thr Gly Pro Lys Gly Asp Pro Gly Ile Pro Gly Leu Asp Arg 835 840 845 Ser Gly Phe Pro Gly Glu Thr Gly Ser Pro Gly Ile Pro Gly His Gln 850 855 860 Gly Glu Met Gly Pro Leu Gly Gln Arg Gly Tyr Pro Gly Asn Pro Gly 865 870 875 880 Ile Leu Gly Pro Pro Gly Glu Asp Gly Val Ile Gly Met Met Gly Phe 885 890 895 Pro Gly Ala Ile Gly Pro Pro Gly Pro Pro Gly Asn Pro Gly Thr Pro 900 905 910 Gly Gln Arg Gly Ser Pro Gly Ile Pro Gly Val Lys Gly Gln Arg Gly 915 920 925 Thr Pro Gly Ala Lys Gly Glu Gln Gly Asp Lys Gly Asn Pro Gly Pro 930 935 940 Ser Glu Ile Ser His Val Ile Gly Asp Lys Gly Glu Pro Gly Leu Lys 945 950 955 960 Gly Phe Ala Gly Asn Pro Gly Glu Lys Gly Asn Arg Gly Val Pro Gly 965 970 975 Met Pro Gly Leu Lys Gly Leu Lys Gly Leu Pro Gly Pro Ala Gly Pro 980 985 990 Pro Gly Pro Arg Gly Asp Leu Gly Ser Thr Gly Asn Pro Gly Glu Pro 995 1000 1005 Gly Leu Arg Gly Ile Pro Gly Ser Met Gly Asn Met Gly Met Pro Gly 1010 1015 1020 Ser Lys Gly Lys Arg Gly Thr Leu Gly Phe Pro Gly Arg Ala Gly Arg 1025 1030 1035 1040 Pro Gly Leu Pro Gly Ile His Gly Leu Gln Gly Asp Lys Gly Glu Pro 1045 1050 1055 Gly Tyr Ser Glu Gly Thr Arg Pro Gly Pro Pro Gly Pro Thr Gly Asp 1060 1065 1070 Pro Gly Leu Pro Gly Asp Met Gly Lys Lys Gly Glu Met Gly Gln Pro 1075 1080 1085 Gly Pro Pro Gly His Leu Gly Pro Ala Gly Pro Glu Gly Ala Pro Gly 1090 1095 1100 Ser Pro Gly Ser Pro Gly Leu Pro Gly Lys Pro Gly Pro His Gly Asp 1105 1110 1115 1120 Leu Gly Phe Lys Gly Ile Lys Gly Leu Leu Gly Pro Pro Gly Ile Arg 1125 1130 1135 Gly Pro Pro Gly Leu Pro Gly Phe Pro Gly Ser Pro Gly Pro Met Gly 1140 1145 1150 Ile Arg Gly Asp Gln Gly Arg Asp Gly Ile Pro Gly Pro Ala Gly Glu 1155 1160 1165 Lys Gly Glu Thr Gly Leu Leu Arg Ala Pro Pro Gly Pro Arg Gly Asn 1170 1175 1180 Pro Gly Ala Gln Gly Ala Lys Gly Asp Arg Gly Ala Pro Gly Phe Pro 1185 1190 1195 1200 Gly Leu Pro Gly Arg Lys Gly Ala Met Gly Asp Ala Gly Pro Arg Gly 1205 1210 1215 Pro Thr Gly Ile Glu Gly Phe Pro Gly Pro Pro Gly Leu Pro Gly Ala 1220 1225 1230 Ile Ile Pro Gly Gln Thr Gly Asn Arg Gly Pro Pro Gly Ser Arg Gly 1235 1240 1245 Ser Pro Gly Ala Pro Gly Pro Pro Gly Pro Pro Gly Ser His Val Ile 1250 1255 1260 Gly Ile Lys Gly Asp Lys Gly Ser Met Gly His Pro Gly Pro Lys Gly 1265 1270 1275 1280 Pro Pro Gly Thr Ala Gly Asp Met Gly Pro Pro Gly Arg Leu Gly Ala 1285 1290 1295 Pro Gly Thr Pro Gly Leu Pro Gly Pro Arg Gly Asp Pro Gly Phe Gln 1300 1305 1310 Gly Phe Pro Gly Val Lys Gly Glu Lys Gly Asn Pro Gly Phe Leu Gly 1315 1320 1325 Ser Ile Gly Pro Pro Gly Pro Ile Gly Pro Lys Gly Pro Pro Gly Val 1330 1335 1340 Arg Gly Asp Pro Gly Thr Leu Lys Ile Ile Ser Leu Pro Gly Ser Pro 1345 1350 1355 1360 Gly Pro Pro Gly Thr Pro Gly Glu Pro Gly Met Gln Gly Glu Pro Gly 1365 1370 1375 Pro Pro Gly Pro Pro Gly Asn Leu Gly Pro Cys Gly Pro Arg Gly Lys 1380 1385 1390 Pro Gly Lys Asp Gly Lys Pro Gly Thr Pro Gly Pro Ala Gly Glu Lys 1395 1400 1405 Gly Asn Lys Gly Ser Lys Gly Glu Pro Gly Pro Ala Gly Ser Asp Gly 1410 1415 1420 Leu Pro Gly Leu Lys Gly Lys Arg Gly Asp Ser Gly Ser Pro Ala Thr 1425 1430 1435 1440 Trp Thr Thr Arg Gly Phe Val Phe Thr Arg His Ser Gln Thr Thr Ala 1445 1450 1455 Ile Pro Ser Cys Pro Glu Gly Thr Val Pro Leu Tyr Ser Gly Phe Ser 1460 1465 1470 Phe Leu Phe Val Gln Gly Asn Gln Arg Ala His Gly Gln Asp Leu Gly 1475 1480 1485 Thr Leu Gly Ser Cys Leu Gln Arg Phe Thr Thr Met Pro Phe Leu Phe 1490 1495 1500 Cys Asn Val Asn Asp Val Cys Asn Phe Ala Ser Arg Asn Asp Tyr Ser 1505 1510 1515 1520 Tyr Trp Leu Ser Thr Pro Ala Leu Met Pro Met Asn Met Ala Pro Ile 1525 1530 1535 Thr Gly Arg Ala Leu Glu Pro Tyr Ile Ser Arg Cys Thr Val Cys Glu 1540 1545 1550 Gly Pro Ala Ile Ala Ile Ala Val His Ser Gln Thr Thr Asp Ile Pro 1555 1560 1565 Pro Cys Pro His Gly Trp Ile Ser Leu Trp Lys Gly Phe Ser Phe Ile 1570 1575 1580 Met Phe Thr Ser Ala Gly Ser Glu Gly Thr Gly Gln Ala Leu Ala Ser 1585 1590 1595 1600 Pro Gly Ser Cys Leu Glu Glu Phe Arg Ala Ser Pro Phe Leu Glu Cys 1605 1610 1615 His Gly Arg Gly Thr Cys Asn Tyr Tyr Ser Asn Ser Tyr Ser Phe Trp 1620 1625 1630 Leu Ala Ser Leu Asn Pro Glu Arg Met Phe Arg Lys Pro Ile Pro Ser 1635 1640 1645 Thr Val Lys Ala Gly Glu Leu Glu Lys Ile Ile Ser Arg Cys Gln Val 1650 1655 1660 Cys Met Lys Lys Arg His 1665 1670 <210> SEQ ID NO 84 <211> LENGTH: 1712 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 84 Met Gly Arg Asp Gln Arg Ala Val Ala Gly Pro Ala Leu Arg Arg Trp 1 5 10 15 Leu Leu Leu Gly Thr Val Thr Val Gly Phe Leu Ala Gln Ser Val Leu 20 25 30 Ala Gly Val Lys Lys Phe Asp Val Pro Cys Gly Gly Arg Asp Cys Ser 35 40 45 Gly Gly Cys Gln Cys Tyr Pro Glu Lys Gly Gly Arg Gly Gln Pro Gly 50 55 60 Pro Val Gly Pro Gln Gly Tyr Asn Gly Pro Pro Gly Leu Gln Gly Phe 65 70 75 80 Pro Gly Leu Gln Gly Arg Lys Gly Asp Lys Gly Glu Arg Gly Ala Pro 85 90 95 Gly Val Thr Gly Pro Lys Gly Asp Val Gly Ala Arg Gly Val Ser Gly 100 105 110 Phe Pro Gly Ala Asp Gly Ile Pro Gly His Pro Gly Gln Gly Gly Pro 115 120 125 Arg Gly Arg Pro Gly Tyr Asp Gly Cys Asn Gly Thr Gln Gly Asp Ser 130 135 140 Gly Pro Gln Gly Pro Pro Gly Ser Glu Gly Phe Thr Gly Pro Pro Gly 145 150 155 160 Pro Gln Gly Pro Lys Gly Gln Lys Gly Glu Pro Tyr Ala Leu Pro Lys 165 170 175 Glu Glu Arg Asp Arg Tyr Arg Gly Glu Pro Gly Glu Pro Gly Leu Val 180 185 190 Gly Phe Gln Gly Pro Pro Gly Arg Pro Gly His Val Gly Gln Met Gly 195 200 205 Pro Val Gly Ala Pro Gly Arg Pro Gly Pro Pro Gly Pro Pro Gly Pro 210 215 220 Lys Gly Gln Gln Gly Asn Arg Gly Leu Gly Phe Tyr Gly Val Lys Gly 225 230 235 240 Glu Lys Gly Asp Val Gly Gln Pro Gly Pro Asn Gly Ile Pro Ser Asp 245 250 255 Thr Leu His Pro Ile Ile Ala Pro Thr Gly Val Thr Phe His Pro Asp 260 265 270 Gln Tyr Lys Gly Glu Lys Gly Ser Glu Gly Glu Pro Gly Ile Arg Gly 275 280 285 Ile Ser Leu Lys Gly Glu Glu Gly Ile Met Gly Phe Pro Gly Leu Arg 290 295 300 Gly Tyr Pro Gly Leu Ser Gly Glu Lys Gly Ser Pro Gly Gln Lys Gly 305 310 315 320 Ser Arg Gly Leu Asp Gly Tyr Gln Gly Pro Asp Gly Pro Arg Gly Pro 325 330 335 Lys Gly Glu Ala Gly Asp Pro Gly Pro Pro Gly Leu Pro Ala Tyr Ser 340 345 350 Pro His Pro Ser Leu Ala Lys Gly Ala Arg Gly Asp Pro Gly Phe Pro 355 360 365 Gly Ala Gln Gly Glu Pro Gly Ser Gln Gly Glu Pro Gly Asp Pro Gly 370 375 380 Leu Pro Gly Pro Pro Gly Leu Ser Ile Gly Asp Gly Asp Gln Arg Arg 385 390 395 400 Gly Leu Pro Gly Glu Met Gly Pro Lys Gly Phe Ile Gly Asp Pro Gly 405 410 415 Ile Pro Ala Leu Tyr Gly Gly Pro Pro Gly Pro Asp Gly Lys Arg Gly 420 425 430 Pro Pro Gly Pro Pro Gly Leu Pro Gly Pro Pro Gly Pro Asp Gly Phe 435 440 445 Leu Phe Gly Leu Lys Gly Ala Lys Gly Arg Ala Gly Phe Pro Gly Leu 450 455 460 Pro Gly Ser Pro Gly Ala Arg Gly Pro Lys Gly Trp Lys Gly Asp Ala 465 470 475 480 Gly Glu Cys Arg Cys Thr Glu Gly Asp Glu Ala Ile Lys Gly Leu Pro 485 490 495 Gly Leu Pro Gly Pro Lys Gly Phe Ala Gly Ile Asn Gly Glu Pro Gly 500 505 510 Arg Lys Gly Asp Arg Gly Asp Pro Gly Gln His Gly Leu Pro Gly Phe 515 520 525 Pro Gly Leu Lys Gly Val Pro Gly Asn Ile Gly Ala Pro Gly Pro Lys 530 535 540 Gly Ala Lys Gly Asp Ser Arg Thr Ile Thr Thr Lys Gly Glu Arg Gly 545 550 555 560 Gln Pro Gly Val Pro Gly Val Pro Gly Met Lys Gly Asp Asp Gly Ser 565 570 575 Pro Gly Arg Asp Gly Leu Asp Gly Phe Pro Gly Leu Pro Gly Pro Pro 580 585 590 Gly Asp Gly Ile Lys Gly Pro Pro Gly Asp Pro Gly Tyr Pro Gly Ile 595 600 605 Pro Gly Thr Lys Gly Thr Pro Gly Glu Met Gly Pro Pro Gly Leu Gly 610 615 620 Leu Pro Gly Leu Lys Gly Gln Arg Gly Phe Pro Gly Asp Ala Gly Leu 625 630 635 640 Pro Gly Pro Pro Gly Phe Leu Gly Pro Pro Gly Pro Ala Gly Thr Pro 645 650 655 Gly Gln Ile Asp Cys Asp Thr Asp Val Lys Arg Ala Val Gly Gly Asp 660 665 670 Arg Gln Glu Ala Ile Gln Pro Gly Cys Ile Gly Gly Pro Lys Gly Leu 675 680 685 Pro Gly Leu Pro Gly Pro Pro Gly Pro Thr Gly Ala Lys Gly Leu Arg 690 695 700 Gly Ile Pro Gly Phe Ala Gly Ala Asp Gly Gly Pro Gly Pro Arg Gly 705 710 715 720 Leu Pro Gly Asp Ala Gly Arg Glu Gly Phe Pro Gly Pro Pro Gly Phe 725 730 735 Ile Gly Pro Arg Gly Ser Lys Gly Ala Val Gly Leu Pro Gly Pro Asp 740 745 750 Gly Ser Pro Gly Pro Ile Gly Leu Pro Gly Pro Asp Gly Pro Pro Gly 755 760 765 Glu Arg Gly Leu Pro Gly Glu Val Leu Gly Ala Gln Pro Gly Pro Arg 770 775 780 Gly Asp Ala Gly Val Pro Gly Gln Pro Gly Leu Lys Gly Leu Pro Gly 785 790 795 800 Asp Arg Gly Pro Pro Gly Phe Arg Gly Ser Gln Gly Met Pro Gly Met 805 810 815 Pro Gly Leu Lys Gly Gln Pro Gly Leu Pro Gly Pro Ser Gly Gln Pro 820 825 830 Gly Leu Tyr Gly Pro Pro Gly Leu His Gly Phe Pro Gly Ala Pro Gly 835 840 845 Gln Glu Gly Pro Leu Gly Leu Pro Gly Ile Pro Gly Arg Glu Gly Leu 850 855 860 Pro Gly Asp Arg Gly Asp Pro Gly Asp Thr Gly Ala Pro Gly Pro Val 865 870 875 880 Gly Met Lys Gly Leu Ser Gly Asp Arg Gly Asp Ala Gly Phe Thr Gly 885 890 895 Glu Gln Gly His Pro Gly Ser Pro Gly Phe Lys Gly Ile Asp Gly Met 900 905 910 Pro Gly Thr Pro Gly Leu Lys Gly Asp Arg Gly Ser Pro Gly Met Asp 915 920 925 Gly Phe Gln Gly Met Pro Gly Leu Lys Gly Arg Pro Gly Phe Pro Gly 930 935 940 Ser Lys Gly Glu Ala Gly Phe Phe Gly Ile Pro Gly Leu Lys Gly Leu 945 950 955 960 Ala Gly Glu Pro Gly Phe Lys Gly Ser Arg Gly Asp Pro Gly Pro Pro 965 970 975 Gly Pro Pro Pro Val Ile Leu Pro Gly Met Lys Asp Ile Lys Gly Glu 980 985 990 Lys Gly Asp Glu Gly Pro Met Gly Leu Lys Gly Tyr Leu Gly Ala Lys 995 1000 1005 Gly Ile Gln Gly Met Pro Gly Ile Pro Gly Leu Ser Gly Ile Pro Gly 1010 1015 1020 Leu Pro Gly Arg Pro Gly His Ile Lys Gly Val Lys Gly Asp Ile Gly 1025 1030 1035 1040 Val Pro Gly Ile Pro Gly Leu Pro Gly Phe Pro Gly Val Ala Gly Pro 1045 1050 1055 Pro Gly Ile Thr Gly Phe Pro Gly Phe Ile Gly Ser Arg Gly Asp Lys 1060 1065 1070 Gly Ala Pro Gly Arg Ala Gly Leu Tyr Gly Glu Ile Gly Ala Thr Gly 1075 1080 1085 Asp Phe Gly Asp Ile Gly Asp Thr Ile Asn Leu Pro Gly Arg Pro Gly 1090 1095 1100 Leu Lys Gly Glu Arg Gly Thr Thr Gly Ile Pro Gly Leu Lys Gly Phe 1105 1110 1115 1120 Phe Gly Glu Lys Gly Thr Glu Gly Asp Ile Gly Phe Pro Gly Ile Thr 1125 1130 1135 Gly Val Thr Gly Val Gln Gly Pro Pro Gly Leu Lys Gly Gln Thr Gly 1140 1145 1150 Phe Pro Gly Leu Thr Gly Pro Pro Gly Ser Gln Gly Glu Leu Gly Arg 1155 1160 1165 Ile Gly Leu Pro Gly Gly Lys Gly Asp Asp Gly Trp Pro Gly Ala Pro 1170 1175 1180 Gly Leu Pro Gly Phe Pro Gly Leu Arg Gly Ile Arg Gly Leu His Gly 1185 1190 1195 1200 Leu Pro Gly Thr Lys Gly Phe Pro Gly Ser Pro Gly Ser Asp Ile His 1205 1210 1215 Gly Asp Pro Gly Phe Pro Gly Pro Pro Gly Glu Arg Gly Asp Pro Gly 1220 1225 1230 Glu Ala Asn Thr Leu Pro Gly Pro Val Gly Val Pro Gly Gln Lys Gly 1235 1240 1245 Asp Gln Gly Ala Pro Gly Glu Arg Gly Pro Pro Gly Ser Pro Gly Leu 1250 1255 1260 Gln Gly Phe Pro Gly Ile Thr Pro Pro Ser Asn Ile Ser Gly Ala Pro 1265 1270 1275 1280 Gly Asp Lys Gly Ala Pro Gly Ile Phe Gly Leu Lys Gly Tyr Arg Gly 1285 1290 1295 Pro Pro Gly Pro Pro Gly Ser Ala Ala Leu Pro Gly Ser Lys Gly Asp 1300 1305 1310 Thr Gly Asn Pro Gly Ala Pro Gly Thr Pro Gly Thr Lys Gly Trp Ala 1315 1320 1325 Gly Asp Ser Gly Pro Gln Gly Arg Pro Gly Val Phe Gly Leu Pro Gly 1330 1335 1340 Glu Lys Gly Pro Arg Gly Glu Gln Gly Phe Met Gly Asn Thr Gly Pro 1345 1350 1355 1360 Thr Gly Ala Val Gly Asp Arg Gly Pro Lys Gly Pro Lys Gly Asp Pro 1365 1370 1375 Gly Phe Pro Gly Ala Pro Gly Thr Val Gly Ala Pro Gly Ile Ala Gly 1380 1385 1390 Ile Pro Gln Lys Ile Ala Val Gln Pro Gly Thr Val Gly Pro Gln Gly 1395 1400 1405 Arg Arg Gly Pro Pro Gly Ala Pro Gly Glu Met Gly Pro Gln Gly Pro 1410 1415 1420 Pro Gly Glu Pro Gly Phe Arg Gly Ala Pro Gly Lys Ala Gly Pro Gln 1425 1430 1435 1440 Gly Arg Gly Gly Val Ser Ala Val Pro Gly Phe Arg Gly Asp Glu Gly 1445 1450 1455 Pro Ile Gly His Gln Gly Pro Ile Gly Gln Glu Gly Ala Pro Gly Arg 1460 1465 1470 Pro Gly Ser Pro Gly Leu Pro Gly Met Pro Gly Arg Ser Val Ser Ile 1475 1480 1485 Gly Tyr Leu Leu Val Lys His Ser Gln Thr Asp Gln Glu Pro Met Cys 1490 1495 1500 Pro Val Gly Met Asn Lys Leu Trp Ser Gly Tyr Ser Leu Leu Tyr Phe 1505 1510 1515 1520 Glu Gly Gln Glu Lys Ala His Asn Gln Asp Leu Gly Leu Ala Gly Ser 1525 1530 1535 Cys Leu Ala Arg Phe Ser Thr Met Pro Phe Leu Tyr Cys Asn Pro Gly 1540 1545 1550 Asp Val Cys Tyr Tyr Ala Ser Arg Asn Asp Lys Ser Tyr Trp Leu Ser 1555 1560 1565 Thr Thr Ala Pro Leu Pro Met Met Pro Val Ala Glu Asp Glu Ile Lys 1570 1575 1580 Pro Tyr Ile Ser Arg Cys Ser Val Cys Glu Ala Pro Ala Ile Ala Ile 1585 1590 1595 1600 Ala Val His Ser Gln Asp Val Ser Ile Pro His Cys Pro Ala Gly Trp 1605 1610 1615 Arg Ser Leu Trp Ile Gly Tyr Ser Phe Leu Met His Thr Ala Ala Gly 1620 1625 1630 Asp Glu Gly Gly Gly Gln Ser Leu Val Ser Pro Gly Ser Cys Leu Glu 1635 1640 1645 Asp Phe Arg Ala Thr Pro Phe Ile Glu Cys Asn Gly Gly Arg Gly Thr 1650 1655 1660 Cys His Tyr Tyr Ala Asn Lys Tyr Ser Phe Trp Leu Thr Thr Ile Pro 1665 1670 1675 1680 Glu Gln Ser Phe Gln Gly Ser Pro Ser Ala Asp Thr Leu Lys Ala Gly 1685 1690 1695 Leu Ile Arg Thr His Ile Ser Arg Cys Gln Val Cys Met Lys Asn Leu 1700 1705 1710 <210> SEQ ID NO 85 <211> LENGTH: 1427 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 85 Met Ser Met Leu Lys Pro Ser Gly Leu Lys Ala Pro Thr Lys Ile Leu 1 5 10 15 Lys Pro Gly Ser Thr Ala Leu Lys Thr Pro Thr Ala Val Val Ala Pro 20 25 30 Val Glu Lys Thr Ile Ser Ser Glu Lys Ala Ser Ser Thr Pro Ser Ser 35 40 45 Glu Thr Gln Glu Glu Phe Val Asp Asp Phe Arg Val Gly Glu Arg Val 50 55 60 Trp Val Asn Gly Asn Lys Pro Gly Phe Ile Gln Phe Leu Gly Glu Thr 65 70 75 80 Gln Phe Ala Pro Gly Gln Trp Ala Gly Ile Val Leu Asp Glu Pro Ile 85 90 95 Gly Lys Asn Asp Gly Ser Val Ala Gly Val Arg Tyr Phe Gln Cys Glu 100 105 110 Pro Leu Lys Gly Ile Phe Thr Arg Pro Ser Lys Leu Thr Arg Lys Val 115 120 125 Gln Ala Glu Asp Glu Ala Asn Gly Leu Gln Thr Thr Pro Ala Ser Arg 130 135 140 Ala Thr Ser Pro Leu Cys Thr Ser Thr Ala Ser Met Val Ser Ser Ser 145 150 155 160 Pro Ser Thr Pro Ser Asn Ile Pro Gln Lys Pro Ser Gln Pro Ala Ala 165 170 175 Lys Glu Pro Ser Ala Thr Pro Pro Ile Ser Asn Leu Thr Lys Thr Ala 180 185 190 Ser Glu Ser Ile Ser Asn Leu Ser Glu Ala Gly Ser Ile Lys Lys Gly 195 200 205 Glu Arg Glu Leu Lys Ile Gly Asp Arg Val Leu Val Gly Gly Thr Lys 210 215 220 Ala Gly Val Val Arg Phe Leu Gly Glu Thr Asp Phe Ala Lys Gly Glu 225 230 235 240 Trp Cys Gly Val Glu Leu Asp Glu Pro Leu Gly Lys Asn Asp Gly Ala 245 250 255 Val Ala Gly Thr Arg Tyr Phe Gln Cys Gln Pro Lys Tyr Gly Leu Phe 260 265 270 Ala Pro Val His Lys Val Thr Lys Ile Gly Phe Pro Ser Thr Thr Pro 275 280 285 Ala Lys Ala Lys Ala Asn Ala Val Arg Arg Val Met Ala Thr Thr Ser 290 295 300 Ala Ser Leu Lys Arg Ser Pro Ser Ala Ser Ser Leu Ser Ser Met Ser 305 310 315 320 Ser Val Ala Ser Ser Val Ser Ser Arg Pro Ser Arg Thr Gly Leu Leu 325 330 335 Thr Glu Thr Ser Ser Arg Tyr Ala Arg Lys Ile Ser Gly Thr Thr Ala 340 345 350 Leu Gln Glu Ala Leu Lys Glu Lys Gln Gln His Ile Glu Gln Leu Leu 355 360 365 Ala Glu Arg Asp Leu Glu Arg Ala Glu Val Ala Lys Ala Thr Ser His 370 375 380 Val Gly Glu Ile Glu Gln Glu Leu Ala Leu Ala Arg Asp Gly His Asp 385 390 395 400 Gln His Val Leu Glu Leu Glu Ala Lys Met Asp Gln Leu Arg Thr Met 405 410 415 Val Glu Ala Ala Asp Arg Glu Lys Val Glu Leu Leu Asn Gln Leu Glu 420 425 430 Glu Glu Lys Arg Lys Val Glu Asp Leu Gln Phe Arg Val Glu Glu Glu 435 440 445 Ser Ile Thr Lys Gly Asp Leu Glu Thr Gln Thr Lys Leu Glu His Ala 450 455 460 Arg Ile Lys Glu Leu Glu Gln Ser Leu Leu Phe Glu Lys Thr Lys Ala 465 470 475 480 Asp Lys Leu Gln Arg Glu Leu Glu Asp Thr Arg Val Ala Thr Val Ser 485 490 495 Glu Lys Ser Arg Ile Met Glu Leu Glu Lys Asp Leu Ala Leu Arg Val 500 505 510 Gln Glu Val Ala Glu Leu Arg Arg Arg Leu Glu Ser Asn Lys Pro Ala 515 520 525 Gly Asp Val Asp Met Ser Leu Ser Leu Leu Gln Glu Ile Ser Ser Leu 530 535 540 Gln Glu Lys Leu Glu Val Thr Arg Thr Asp His Gln Arg Glu Ile Thr 545 550 555 560 Ser Leu Lys Glu His Phe Gly Ala Arg Glu Glu Thr His Gln Lys Glu 565 570 575 Ile Lys Ala Leu Tyr Thr Ala Thr Glu Lys Leu Ser Lys Glu Asn Glu 580 585 590 Ser Leu Lys Ser Lys Leu Glu His Ala Asn Lys Glu Asn Ser Asp Val 595 600 605 Ile Ala Leu Trp Lys Ser Lys Leu Glu Thr Ala Ile Ala Ser His Gln 610 615 620 Gln Ala Met Glu Glu Leu Lys Val Ser Phe Ser Lys Gly Leu Gly Thr 625 630 635 640 Glu Thr Ala Glu Phe Ala Glu Leu Lys Thr Gln Ile Glu Lys Met Arg 645 650 655 Leu Asp Tyr Gln His Glu Ile Glu Asn Leu Gln Asn Gln Gln Asp Ser 660 665 670 Glu Arg Ala Ala His Ala Lys Glu Met Glu Ala Leu Arg Ala Lys Leu 675 680 685 Met Lys Val Ile Lys Glu Lys Glu Asn Ser Leu Glu Ala Ile Arg Ser 690 695 700 Lys Leu Asp Lys Ala Glu Asp Gln His Leu Val Glu Met Glu Asp Thr 705 710 715 720 Leu Asn Lys Leu Gln Glu Ala Glu Ile Lys Val Lys Glu Leu Glu Val 725 730 735 Leu Gln Ala Lys Cys Asn Glu Gln Thr Lys Val Ile Asp Asn Phe Thr 740 745 750 Ser Gln Leu Lys Ala Thr Glu Glu Lys Leu Leu Asp Leu Asp Ala Leu 755 760 765 Arg Lys Ala Ser Ser Glu Gly Lys Ser Glu Met Lys Lys Leu Arg Gln 770 775 780 Gln Leu Glu Ala Ala Glu Lys Gln Ile Lys His Leu Glu Ile Glu Lys 785 790 795 800 Asn Ala Glu Ser Ser Lys Ala Ser Ser Ile Thr Arg Glu Leu Gln Gly 805 810 815 Arg Glu Leu Lys Leu Thr Asn Leu Gln Glu Asn Leu Ser Glu Val Ser 820 825 830 Gln Val Lys Glu Thr Leu Glu Lys Glu Leu Gln Ile Leu Lys Glu Lys 835 840 845 Phe Ala Glu Ala Ser Glu Glu Ala Val Ser Val Gln Arg Ser Met Gln 850 855 860 Glu Thr Val Asn Lys Leu His Gln Lys Glu Glu Gln Phe Asn Met Leu 865 870 875 880 Ser Ser Asp Leu Glu Lys Leu Arg Glu Asn Leu Ala Asp Met Glu Ala 885 890 895 Lys Phe Arg Glu Lys Asp Glu Arg Glu Glu Gln Leu Ile Lys Ala Lys 900 905 910 Glu Lys Leu Glu Asn Asp Ile Ala Glu Ile Met Lys Met Ser Gly Asp 915 920 925 Asn Ser Ser Gln Leu Thr Lys Met Asn Asp Glu Leu Arg Leu Lys Glu 930 935 940 Arg Asp Val Glu Glu Leu Gln Leu Lys Leu Thr Lys Ala Asn Glu Asn 945 950 955 960 Ala Ser Phe Leu Gln Lys Ser Ile Glu Asp Met Thr Val Lys Ala Glu 965 970 975 Gln Ser Gln Gln Glu Ala Ala Lys Lys His Glu Glu Glu Lys Lys Glu 980 985 990 Leu Glu Arg Lys Leu Ser Asp Leu Glu Lys Lys Met Glu Thr Ser His 995 1000 1005 Asn Gln Cys Gln Glu Leu Lys Ala Arg Tyr Glu Arg Ala Thr Ser Glu 1010 1015 1020 Thr Lys Thr Lys His Glu Glu Ile Leu Gln Asn Leu Gln Lys Thr Leu 1025 1030 1035 1040 Leu Asp Thr Glu Asp Lys Leu Lys Gly Ala Arg Glu Glu Asn Ser Gly 1045 1050 1055 Leu Leu Gln Glu Leu Glu Glu Leu Arg Lys Gln Ala Asp Lys Ala Lys 1060 1065 1070 Ala Ala Gln Thr Ala Glu Asp Ala Met Gln Ile Met Glu Gln Met Thr 1075 1080 1085 Lys Glu Lys Thr Glu Thr Leu Ala Ser Leu Glu Asp Thr Lys Gln Thr 1090 1095 1100 Asn Ala Lys Leu Gln Asn Glu Leu Asp Thr Leu Lys Glu Asn Asn Leu 1105 1110 1115 1120 Lys Asn Val Glu Glu Leu Asn Lys Ser Lys Glu Leu Leu Thr Val Glu 1125 1130 1135 Asn Gln Lys Met Glu Glu Phe Arg Lys Glu Ile Glu Thr Leu Lys Gln 1140 1145 1150 Ala Ala Ala Gln Lys Ser Gln Gln Leu Ser Ala Leu Gln Glu Glu Asn 1155 1160 1165 Val Lys Leu Ala Glu Glu Leu Gly Arg Ser Arg Asp Glu Val Thr Ser 1170 1175 1180 His Gln Lys Leu Glu Glu Glu Arg Ser Val Leu Asn Asn Gln Leu Leu 1185 1190 1195 1200 Glu Met Lys Lys Arg Glu Ser Lys Phe Ile Lys Asp Ala Asp Glu Glu 1205 1210 1215 Lys Ala Ser Leu Gln Lys Ser Ile Ser Ile Thr Ser Ala Leu Leu Thr 1220 1225 1230 Glu Lys Asp Ala Glu Leu Glu Lys Leu Arg Asn Glu Val Thr Val Leu 1235 1240 1245 Arg Gly Glu Asn Ala Ser Ala Lys Ser Leu His Ser Val Val Gln Thr 1250 1255 1260 Leu Glu Ser Asp Lys Val Lys Leu Glu Leu Lys Val Lys Asn Leu Glu 1265 1270 1275 1280 Leu Gln Leu Lys Glu Asn Lys Arg Gln Leu Ser Ser Ser Ser Gly Asn 1285 1290 1295 Thr Asp Thr Gln Ala Asp Glu Asp Glu Arg Ala Gln Glu Ser Gln Ile 1300 1305 1310 Asp Phe Leu Asn Ser Val Ile Val Asp Leu Gln Arg Lys Asn Gln Asp 1315 1320 1325 Leu Lys Met Lys Val Glu Met Met Ser Glu Ala Ala Leu Asn Gly Asn 1330 1335 1340 Gly Asp Asp Leu Asn Asn Tyr Asp Ser Asp Asp Gln Glu Lys Gln Ser 1345 1350 1355 1360 Lys Lys Lys Pro Arg Leu Phe Cys Asp Ile Cys Asp Cys Phe Asp Leu 1365 1370 1375 His Asp Thr Glu Asp Cys Pro Thr Gln Ala Gln Met Ser Glu Asp Pro 1380 1385 1390 Pro His Ser Thr His His Gly Ser Arg Gly Glu Glu Arg Pro Tyr Cys 1395 1400 1405 Glu Ile Cys Glu Met Phe Gly His Trp Ala Thr Asn Cys Asn Asp Asp 1410 1415 1420 Glu Thr Phe 1425 <210> SEQ ID NO 86 <211> LENGTH: 251 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 86 Met Ala Glu Asp Leu Gly Leu Ser Phe Gly Glu Thr Ala Ser Val Glu 1 5 10 15 Met Leu Pro Glu His Gly Ser Cys Arg Pro Lys Ala Arg Ser Ser Ser 20 25 30 Ala Arg Trp Ala Leu Thr Cys Cys Leu Val Leu Leu Pro Phe Leu Ala 35 40 45 Gly Leu Thr Thr Tyr Leu Leu Val Ser Gln Leu Arg Ala Gln Gly Glu 50 55 60 Ala Cys Val Gln Phe Gln Ala Leu Lys Gly Gln Glu Phe Ala Pro Ser 65 70 75 80 His Gln Gln Val Tyr Ala Pro Leu Arg Ala Asp Gly Asp Lys Pro Arg 85 90 95 Ala His Leu Thr Val Val Arg Gln Thr Pro Thr Gln His Phe Lys Asn 100 105 110 Gln Phe Pro Ala Leu His Trp Glu His Glu Leu Gly Leu Ala Phe Thr 115 120 125 Lys Asn Arg Met Asn Tyr Thr Asn Lys Phe Leu Leu Ile Pro Glu Ser 130 135 140 Gly Asp Tyr Phe Ile Tyr Ser Gln Val Thr Phe Arg Gly Met Thr Ser 145 150 155 160 Glu Cys Ser Glu Ile Arg Gln Ala Gly Arg Pro Asn Lys Pro Asp Ser 165 170 175 Ile Thr Val Val Ile Thr Lys Val Thr Asp Ser Tyr Pro Glu Pro Thr 180 185 190 Gln Leu Leu Met Gly Thr Lys Ser Val Cys Glu Val Gly Ser Asn Trp 195 200 205 Phe Gln Pro Ile Tyr Leu Gly Ala Met Phe Ser Leu Gln Glu Gly Asp 210 215 220 Lys Leu Met Val Asn Val Ser Asp Ile Ser Leu Val Asp Tyr Thr Lys 225 230 235 240 Glu Asp Lys Thr Phe Phe Gly Ala Phe Leu Leu 245 250 <210> SEQ ID NO 87 <211> LENGTH: 498 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 87 Met Thr Val Phe Leu Ser Phe Ala Phe Leu Ala Ala Ile Leu Thr His 1 5 10 15 Ile Gly Cys Ser Asn Gln Arg Arg Ser Pro Glu Asn Ser Gly Arg Arg 20 25 30 Tyr Asn Arg Ile Gln His Gly Gln Cys Ala Tyr Thr Phe Ile Leu Pro 35 40 45 Glu His Asp Gly Asn Cys Arg Glu Ser Thr Thr Asp Gln Tyr Asn Thr 50 55 60 Asn Ala Leu Gln Arg Asp Ala Pro His Val Glu Pro Asp Phe Ser Ser 65 70 75 80 Gln Lys Leu Gln His Leu Glu His Val Met Glu Asn Tyr Thr Gln Trp 85 90 95 Leu Gln Lys Leu Glu Asn Tyr Ile Val Glu Asn Met Lys Ser Glu Met 100 105 110 Ala Gln Ile Gln Gln Asn Ala Val Gln Asn His Thr Ala Thr Met Leu 115 120 125 Glu Ile Gly Thr Ser Leu Leu Ser Gln Thr Ala Glu Gln Thr Arg Lys 130 135 140 Leu Thr Asp Val Glu Thr Gln Val Leu Asn Gln Thr Ser Arg Leu Glu 145 150 155 160 Ile Gln Leu Leu Glu Asn Ser Leu Ser Thr Tyr Lys Leu Glu Lys Gln 165 170 175 Leu Leu Gln Gln Thr Asn Glu Ile Leu Lys Ile His Glu Lys Asn Ser 180 185 190 Leu Leu Glu His Lys Ile Leu Glu Met Glu Gly Lys His Lys Glu Glu 195 200 205 Leu Asp Thr Leu Lys Glu Glu Lys Glu Asn Leu Gln Gly Leu Val Thr 210 215 220 Arg Gln Thr Tyr Ile Ile Gln Glu Leu Glu Lys Gln Leu Asn Arg Ala 225 230 235 240 Thr Thr Asn Asn Ser Val Leu Gln Lys Gln Gln Leu Glu Leu Met Asp 245 250 255 Thr Val His Asn Leu Val Asn Leu Cys Thr Lys Glu Gly Val Leu Leu 260 265 270 Lys Gly Gly Lys Arg Glu Glu Glu Lys Pro Phe Arg Asp Cys Ala Asp 275 280 285 Val Tyr Gln Ala Gly Phe Asn Lys Ser Gly Ile Tyr Thr Ile Tyr Ile 290 295 300 Asn Asn Met Pro Glu Pro Lys Lys Val Phe Cys Asn Met Asp Val Asn 305 310 315 320 Gly Gly Gly Trp Thr Val Ile Gln His Arg Glu Asp Gly Ser Leu Asp 325 330 335 Phe Gln Arg Gly Trp Lys Glu Tyr Lys Met Gly Phe Gly Asn Pro Ser 340 345 350 Gly Glu Tyr Trp Leu Gly Asn Glu Phe Ile Phe Ala Ile Thr Ser Gln 355 360 365 Arg Gln Tyr Met Leu Arg Ile Glu Leu Met Asp Trp Glu Gly Asn Arg 370 375 380 Ala Tyr Ser Gln Tyr Asp Arg Phe His Ile Gly Asn Glu Lys Gln Asn 385 390 395 400 Tyr Arg Leu Tyr Leu Lys Gly His Thr Gly Thr Ala Gly Lys Gln Ser 405 410 415 Ser Leu Ile Leu His Gly Ala Asp Phe Ser Thr Lys Asp Ala Asp Asn 420 425 430 Asp Asn Cys Met Cys Lys Cys Ala Leu Met Leu Thr Gly Gly Trp Trp 435 440 445 Phe Asp Ala Cys Gly Pro Ser Asn Leu Asn Gly Met Phe Tyr Thr Ala 450 455 460 Gly Gln Asn His Gly Lys Leu Asn Gly Ile Lys Trp His Tyr Phe Lys 465 470 475 480 Gly Pro Ser Tyr Ser Leu Arg Ser Thr Thr Met Met Ile Arg Pro Leu 485 490 495 Asp Phe <210> SEQ ID NO 88 <211 > LENGTH: 227 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 88 Met Asn Ile Lys Gly Ser Pro Trp Lys Gly Ser Leu Leu Leu Leu Leu 1 5 10 15 Val Ser Asn Leu Leu Leu Cys Gln Ser Val Ala Pro Leu Pro Ile Cys 20 25 30 Pro Gly Gly Ala Ala Arg Cys Gln Val Thr Leu Arg Asp Leu Phe Asp 35 40 45 Arg Ala Val Val Leu Ser His Tyr Ile His Asn Leu Ser Ser Glu Met 50 55 60 Phe Ser Glu Phe Asp Lys Arg Tyr Thr His Gly Arg Gly Phe Ile Thr 65 70 75 80 Lys Ala Ile Asn Ser Cys His Thr Ser Ser Leu Ala Thr Pro Glu Asp 85 90 95 Lys Glu Gln Ala Gln Gln Met Asn Gln Lys Asp Phe Leu Ser Leu Ile 100 105 110 Val Ser Ile Leu Arg Ser Trp Asn Glu Pro Leu Tyr His Leu Val Thr 115 120 125 Glu Val Arg Gly Met Gln Glu Ala Pro Glu Ala Ile Leu Ser Lys Ala 130 135 140 Val Glu Ile Glu Glu Gln Thr Lys Arg Leu Leu Glu Gly Met Glu Leu 145 150 155 160 Ile Val Ser Gln Val His Pro Glu Thr Lys Glu Asn Glu Ile Tyr Pro 165 170 175 Val Trp Ser Gly Leu Pro Ser Leu Gln Met Ala Asp Glu Glu Ser Arg 180 185 190 Leu Ser Ala Tyr Tyr Asn Leu Leu His Cys Leu Arg Arg Asp Ser His 195 200 205 Lys Ile Asp Asn Tyr Leu Lys Leu Leu Lys Cys Arg Ile Ile His Asn 210 215 220 Asn Asn Cys 225 <210> SEQ ID NO 89 <211> LENGTH: 4391 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 89 Met Gly Trp Arg Ala Ala Gly Ala Leu Leu Leu Ala Leu Leu Leu His 1 5 10 15 Gly Arg Leu Leu Ala Val Thr His Gly Leu Arg Ala Tyr Asp Gly Leu 20 25 30 Ser Leu Pro Glu Asp Ile Glu Thr Val Thr Ala Ser Gln Met Arg Trp 35 40 45 Thr His Ser Tyr Leu Ser Asp Asp Glu Asp Met Leu Ala Asp Ser Ile 50 55 60 Ser Gly Asp Asp Leu Gly Ser Gly Asp Leu Gly Ser Gly Asp Phe Gln 65 70 75 80 Met Val Tyr Phe Arg Ala Leu Val Asn Phe Thr Arg Ser Ile Glu Tyr 85 90 95 Ser Pro Gln Leu Glu Asp Ala Gly Ser Arg Glu Phe Arg Glu Val Ser 100 105 110 Glu Ala Val Val Asp Thr Leu Glu Ser Glu Tyr Leu Lys Ile Pro Gly 115 120 125 Asp Gln Val Val Ser Val Val Phe Ile Lys Glu Leu Asp Gly Trp Val 130 135 140 Phe Val Glu Leu Asp Val Gly Ser Glu Gly Asn Ala Asp Gly Ala Gln 145 150 155 160 Ile Gln Glu Met Leu Leu Arg Val Ile Ser Ser Gly Ser Val Ala Ser 165 170 175 Tyr Val Thr Ser Pro Gln Gly Phe Gln Phe Arg Arg Leu Gly Thr Val 180 185 190 Pro Gln Phe Pro Arg Ala Cys Thr Glu Ala Glu Phe Ala Cys His Ser 195 200 205 Tyr Asn Glu Cys Val Ala Leu Glu Tyr Arg Cys Asp Arg Arg Pro Asp 210 215 220 Cys Arg Asp Met Ser Asp Glu Leu Asn Cys Glu Glu Pro Val Leu Gly 225 230 235 240 Ile Ser Pro Thr Phe Ser Leu Leu Val Glu Thr Thr Ser Leu Pro Pro 245 250 255 Arg Pro Glu Thr Thr Ile Met Arg Gln Pro Pro Val Thr His Ala Pro 260 265 270 Gln Pro Leu Leu Pro Gly Ser Val Arg Pro Leu Pro Cys Gly Pro Gln 275 280 285 Glu Ala Ala Cys Arg Asn Gly His Cys Ile Pro Arg Asp Tyr Leu Cys 290 295 300 Asp Gly Gln Glu Asp Cys Glu Asp Gly Ser Asp Glu Leu Asp Cys Gly 305 310 315 320 Pro Pro Pro Pro Cys Glu Pro Asn Glu Phe Pro Cys Gly Asn Gly His 325 330 335 Cys Ala Leu Lys Leu Trp Arg Cys Asp Gly Asp Phe Asp Cys Glu Asp 340 345 350 Arg Thr Asp Glu Ala Asn Cys Pro Thr Lys Arg Pro Glu Glu Val Cys 355 360 365 Gly Pro Thr Gln Phe Arg Cys Val Ser Thr Asn Met Cys Ile Pro Ala 370 375 380 Ser Phe His Cys Asp Glu Glu Ser Asp Cys Pro Asp Arg Ser Asp Glu 385 390 395 400 Phe Gly Cys Met Pro Pro Gln Val Val Thr Pro Pro Arg Glu Ser Ile 405 410 415 Gln Ala Ser Arg Gly Gln Thr Val Thr Phe Thr Cys Val Ala Ile Gly 420 425 430 Val Pro Thr Pro Ile Ile Asn Trp Arg Leu Asn Trp Gly His Ile Pro 435 440 445 Ser His Pro Arg Val Thr Val Thr Ser Glu Gly Gly Arg Gly Thr Leu 450 455 460 Ile Ile Arg Asp Val Lys Glu Ser Asp Gln Gly Ala Tyr Thr Cys Glu 465 470 475 480 Ala Met Asn Ala Arg Gly Met Val Phe Gly Ile Pro Asp Gly Val Leu 485 490 495 Glu Leu Val Pro Gln Arg Gly Pro Cys Pro Asp Gly His Phe Tyr Leu 500 505 510 Glu His Ser Ala Ala Cys Leu Pro Cys Phe Cys Phe Gly Ile Thr Ser 515 520 525 Val Cys Gln Ser Thr Arg Arg Phe Arg Asp Gln Ile Arg Leu Arg Phe 530 535 540 Asp Gln Pro Asp Asp Phe Lys Gly Val Asn Val Thr Met Pro Ala Gln 545 550 555 560 Pro Gly Thr Pro Pro Leu Ser Ser Thr Gln Leu Gln Ile Asp Pro Ser 565 570 575 Leu His Glu Phe Gln Leu Val Asp Leu Ser Arg Arg Phe Leu Val His 580 585 590 Asp Ser Phe Trp Ala Leu Pro Glu Gln Phe Leu Gly Asn Lys Val Asp 595 600 605 Ser Tyr Gly Gly Ser Leu Arg Tyr Asn Val Arg Tyr Glu Leu Ala Arg 610 615 620 Gly Met Leu Glu Pro Val Gln Arg Pro Asp Val Val Leu Met Gly Ala 625 630 635 640 Gly Tyr Arg Leu Leu Ser Arg Gly His Thr Pro Thr Gln Pro Gly Ala 645 650 655 Leu Asn Gln Arg Gln Val Gln Phe Ser Glu Glu His Trp Val His Glu 660 665 670 Ser Gly Arg Pro Val Gln Arg Ala Glu Leu Leu Gln Val Leu Gln Ser 675 680 685 Leu Glu Ala Val Leu Ile Gln Thr Val Tyr Asn Thr Lys Met Ala Ser 690 695 700 Val Gly Leu Ser Asp Ile Ala Met Asp Thr Thr Val Thr His Ala Thr 705 710 715 720 Ser His Gly Arg Ala His Ser Val Glu Glu Cys Arg Cys Pro Ile Gly 725 730 735 Tyr Ser Gly Leu Ser Cys Glu Ser Cys Asp Ala His Phe Thr Arg Val 740 745 750 Pro Gly Gly Pro Tyr Leu Gly Thr Cys Ser Gly Cys Asn Cys Asn Gly 755 760 765 His Ala Ser Ser Cys Asp Pro Val Tyr Gly His Cys Leu Asn Cys Gln 770 775 780 His Asn Thr Glu Gly Pro Gln Cys Asn Lys Cys Lys Ala Gly Phe Phe 785 790 795 800 Gly Asp Ala Met Lys Ala Thr Ala Thr Ser Cys Arg Pro Cys Pro Cys 805 810 815 Pro Tyr Ile Asp Ala Ser Arg Arg Phe Ser Asp Thr Cys Phe Leu Asp 820 825 830 Thr Asp Gly Gln Ala Thr Cys Asp Ala Cys Ala Pro Gly Tyr Thr Gly 835 840 845 Arg Arg Cys Glu Ser Cys Ala Pro Gly Tyr Glu Gly Asn Pro Ile Gln 850 855 860 Pro Gly Gly Lys Cys Arg Pro Val Asn Gln Glu Ile Val Arg Cys Asp 865 870 875 880 Glu Arg Gly Ser Met Gly Thr Ser Gly Glu Ala Cys Arg Cys Lys Asn 885 890 895 Asn Val Val Gly Arg Leu Cys Asn Glu Cys Ala Asp Gly Ser Phe His 900 905 910 Leu Ser Thr Arg Asn Pro Asp Gly Cys Leu Lys Cys Phe Cys Met Gly 915 920 925 Val Ser Arg His Cys Thr Ser Ser Ser Trp Ser Arg Ala Gln Leu His 930 935 940 Gly Ala Ser Glu Glu Pro Gly His Phe Ser Leu Thr Asn Ala Ala Ser 945 950 955 960 Thr His Thr Thr Asn Glu Gly Ile Phe Ser Pro Thr Pro Gly Glu Leu 965 970 975 Gly Phe Ser Ser Phe His Arg Leu Leu Ser Gly Pro Tyr Phe Trp Ser 980 985 990 Leu Pro Ser Arg Phe Leu Gly Asp Lys Val Thr Ser Tyr Gly Gly Glu 995 1000 1005 Leu Arg Phe Thr Val Thr Gln Arg Ser Gln Pro Gly Ser Thr Pro Leu 1010 1015 1020 His Gly Gln Pro Leu Val Val Leu Gln Gly Asn Asn Ile Ile Leu Glu 1025 1030 1035 1040 His His Val Ala Gln Glu Pro Ser Pro Gly Gln Pro Ser Thr Phe Ile 1045 1050 1055 Val Pro Phe Arg Glu Gln Ala Trp Gln Arg Pro Asp Gly Gln Pro Ala 1060 1065 1070 Thr Arg Glu His Leu Leu Met Ala Leu Ala Gly Ile Asp Thr Leu Leu 1075 1080 1085 Ile Arg Ala Ser Tyr Ala Gln Gln Pro Ala Glu Ser Arg Val Ser Gly 1090 1095 1100 Ile Ser Met Asp Val Ala Val Pro Glu Glu Thr Gly Gln Asp Pro Ala 1105 1110 1115 1120 Leu Glu Val Glu Gln Cys Ser Cys Pro Pro Gly Tyr Arg Gly Pro Ser 1125 1130 1135 Cys Gln Asp Cys Asp Thr Gly Tyr Thr Arg Thr Pro Ser Gly Leu Tyr 1140 1145 1150 Leu Gly Thr Cys Glu Arg Cys Ser Cys His Gly His Ser Glu Ala Cys 1155 1160 1165 Glu Pro Glu Thr Gly Ala Cys Gln Gly Cys Gln His His Thr Glu Gly 1170 1175 1180 Pro Arg Cys Glu Gln Cys Gln Pro Gly Tyr Tyr Gly Asp Ala Gln Arg 1185 1190 1195 1200 Gly Thr Pro Gln Asp Cys Gln Leu Cys Pro Cys Tyr Gly Asp Pro Ala 1205 1210 1215 Ala Gly Gln Ala Ala His Thr Cys Phe Leu Asp Thr Asp Gly His Pro 1220 1225 1230 Thr Cys Asp Ala Cys Ser Pro Gly His Ser Gly Arg His Cys Glu Arg 1235 1240 1245 Cys Ala Pro Gly Tyr Tyr Gly Asn Pro Ser Gln Gly Gln Pro Cys Gln 1250 1255 1260 Arg Asp Ser Gln Val Pro Gly Pro Ile Gly Cys Asn Cys Asp Pro Gln 1265 1270 1275 1280 Gly Ser Val Ser Ser Gln Cys Asp Ala Ala Gly Gln Cys Gln Cys Lys 1285 1290 1295 Ala Gln Val Glu Gly Leu Thr Cys Ser His Cys Arg Pro His His Phe 1300 1305 1310 His Leu Ser Ala Ser Asn Pro Asp Gly Cys Leu Pro Cys Phe Cys Met 1315 1320 1325 Gly Ile Thr Gln Gln Cys Ala Ser Ser Ala Tyr Thr Arg His Leu Ile 1330 1335 1340 Ser Thr His Phe Ala Pro Gly Asp Phe Gln Gly Phe Ala Leu Val Asn 1345 1350 1355 1360 Pro Gln Arg Asn Ser Arg Leu Thr Gly Glu Phe Thr Val Glu Pro Val 1365 1370 1375 Pro Glu Gly Ala Gln Leu Ser Phe Gly Asn Phe Ala Gln Leu Gly His 1380 1385 1390 Glu Ser Phe Tyr Trp Gln Leu Pro Glu Thr Tyr Gln Gly Asp Lys Val 1395 1400 1405 Ala Ala Tyr Gly Gly Lys Leu Arg Tyr Thr Leu Ser Tyr Thr Ala Gly 1410 1415 1420 Pro Gln Gly Ser Pro Leu Ser Asp Pro Asp Val Gln Ile Thr Gly Asn 1425 1430 1435 1440 Asn Ile Met Leu Val Ala Ser Gln Pro Ala Leu Gln Gly Pro Glu Arg 1445 1450 1455 Arg Ser Tyr Glu Ile Met Phe Arg Glu Glu Phe Trp Arg Arg Pro Asp 1460 1465 1470 Gly Gln Pro Ala Thr Arg Glu His Leu Leu Met Ala Leu Ala Asp Leu 1475 1480 1485 Asp Glu Leu Leu Ile Arg Ala Thr Phe Ser Ser Val Pro Leu Ala Ala 1490 1495 1500 Ser Ile Ser Ala Val Ser Leu Glu Val Ala Gln Pro Gly Pro Ser Asn 1505 1510 1515 1520 Arg Pro Arg Ala Leu Glu Val Glu Glu Cys Arg Cys Pro Pro Gly Tyr 1525 1530 1535 Ile Gly Leu Ser Cys Gln Asp Cys Ala Pro Gly Tyr Thr Arg Thr Gly 1540 1545 1550 Ser Gly Leu Tyr Leu Gly His Cys Glu Leu Cys Glu Cys Asn Gly His 1555 1560 1565 Ser Asp Leu Cys His Pro Glu Thr Gly Ala Cys Ser Gln Cys Gln His 1570 1575 1580 Asn Ala Ala Gly Glu Phe Cys Glu Leu Cys Ala Pro Gly Tyr Tyr Gly 1585 1590 1595 1600 Asp Ala Thr Ala Gly Thr Pro Glu Asp Cys Gln Pro Cys Ala Cys Pro 1605 1610 1615 Leu Thr Asn Pro Glu Asn Met Phe Ser Arg Thr Cys Glu Ser Leu Gly 1620 1625 1630 Ala Gly Gly Tyr Arg Cys Thr Ala Cys Glu Pro Gly Tyr Thr Gly Gln 1635 1640 1645 Tyr Cys Glu Gln Cys Gly Pro Gly Tyr Val Gly Asn Pro Ser Val Gln 1650 1655 1660 Gly Gly Gln Cys Leu Pro Glu Thr Asn Gln Ala Pro Leu Val Val Glu 1665 1670 1675 1680 Val His Pro Ala Arg Ser Ile Val Pro Gln Gly Gly Ser His Ser Leu 1685 1690 1695 Arg Cys Gln Val Ser Gly Ser Pro Pro His Tyr Phe Tyr Trp Ser Arg 1700 1705 1710 Glu Asp Gly Arg Pro Val Pro Ser Gly Thr Gln Gln Arg His Gln Gly 1715 1720 1725 Ser Glu Leu His Phe Pro Ser Val Gln Pro Ser Asp Ala Gly Val Tyr 1730 1735 1740 Ile Cys Thr Cys Arg Asn Leu His Gln Ser Asn Thr Ser Arg Ala Glu 1745 1750 1755 1760 Leu Leu Val Thr Glu Ala Pro Ser Lys Pro Ile Thr Val Thr Val Glu 1765 1770 1775 Glu Gln Arg Ser Gln Ser Val Arg Pro Gly Ala Asp Val Thr Phe Ile 1780 1785 1790 Cys Thr Ala Lys Ser Lys Ser Pro Ala Tyr Thr Leu Val Trp Thr Arg 1795 1800 1805 Leu His Asn Gly Lys Leu Pro Thr Arg Ala Met Asp Phe Asn Gly Ile 1810 1815 1820 Leu Thr Ile Arg Asn Val Gln Leu Ser Asp Ala Gly Thr Tyr Val Cys 1825 1830 1835 1840 Thr Gly Ser Asn Met Phe Ala Met Asp Gln Gly Thr Ala Thr Leu His 1845 1850 1855 Val Gln Ala Ser Gly Thr Leu Ser Ala Pro Val Val Ser Ile His Pro 1860 1865 1870 Pro Gln Leu Thr Val Gln Pro Gly Gln Leu Ala Glu Phe Arg Cys Ser 1875 1880 1885 Ala Thr Gly Ser Pro Thr Pro Thr Leu Glu Trp Thr Gly Gly Pro Gly 1890 1895 1900 Gly Gln Leu Pro Ala Lys Ala Gln Ile His Gly Gly Ile Leu Arg Leu 1905 1910 1915 1920 Pro Ala Val Glu Pro Thr Asp Gln Ala Gln Tyr Leu Cys Arg Ala His 1925 1930 1935 Ser Ser Ala Gly Gln Gln Val Ala Arg Ala Val Leu His Val His Gly 1940 1945 1950 Gly Gly Gly Pro Arg Val Gln Val Ser Pro Glu Arg Thr Gln Val His 1955 1960 1965 Ala Gly Arg Thr Val Arg Leu Tyr Cys Arg Ala Ala Gly Val Pro Ser 1970 1975 1980 Ala Thr Ile Thr Trp Arg Lys Glu Gly Gly Ser Leu Pro Pro Gln Ala 1985 1990 1995 2000 Arg Ser Glu Arg Thr Asp Ile Ala Thr Leu Leu Ile Pro Ala Ile Thr 2005 2010 2015 Thr Ala Asp Ala Gly Phe Tyr Leu Cys Val Ala Thr Ser Pro Ala Gly 2020 2025 2030 Thr Ala Gln Ala Arg Ile Gln Val Val Val Leu Ser Ala Ser Asp Ala 2035 2040 2045 Ser Pro Pro Pro Val Lys Ile Glu Ser Ser Ser Pro Ser Val Thr Glu 2050 2055 2060 Gly Gln Thr Leu Asp Leu Asn Cys Val Val Ala Gly Ser Ala His Ala 2065 2070 2075 2080 Gln Val Thr Trp Tyr Arg Arg Gly Gly Ser Leu Pro Pro His Thr Gln 2085 2090 2095 Val His Gly Ser Arg Leu Arg Leu Pro Gln Val Ser Pro Ala Asp Ser 2100 2105 2110 Gly Glu Tyr Val Cys Arg Val Glu Asn Gly Ser Gly Pro Lys Glu Ala 2115 2120 2125 Ser Ile Thr Val Ser Val Leu His Gly Thr His Ser Gly Pro Ser Tyr 2130 2135 2140 Thr Pro Val Pro Gly Ser Thr Arg Pro Ile Arg Ile Glu Pro Ser Ser 2145 2150 2155 2160 Ser His Val Ala Glu Gly Gln Thr Leu Asp Leu Asn Cys Val Val Pro 2165 2170 2175 Gly Gln Ala His Ala Gln Val Thr Trp His Lys Arg Gly Gly Ser Leu 2180 2185 2190 Pro Ala Arg His Gln Thr His Gly Ser Leu Leu Arg Leu His Gln Val 2195 2200 2205 Thr Pro Ala Asp Ser Gly Glu Tyr Val Cys His Val Val Gly Thr Ser 2210 2215 2220 Gly Pro Leu Glu Ala Ser Val Leu Val Thr Ile Glu Ala Ser Val Ile 2225 2230 2235 2240 Pro Gly Pro Ile Pro Pro Val Arg Ile Glu Ser Ser Ser Ser Thr Val 2245 2250 2255 Ala Glu Gly Gln Thr Leu Asp Leu Ser Cys Val Val Ala Gly Gln Ala 2260 2265 2270 His Ala Gln Val Thr Trp Tyr Lys Arg Gly Gly Ser Leu Pro Ala Arg 2275 2280 2285 His Gln Val Arg Gly Ser Arg Leu Tyr Ile Phe Gln Ala Ser Pro Ala 2290 2295 2300 Asp Ala Gly Gln Tyr Val Cys Arg Ala Ser Asn Gly Met Glu Ala Ser 2305 2310 2315 2320 Ile Thr Val Thr Val Thr Gly Thr Gln Gly Ala Asn Leu Ala Tyr Pro 2325 2330 2335 Ala Gly Ser Thr Gln Pro Ile Arg Ile Glu Pro Ser Ser Ser Gln Val 2340 2345 2350 Ala Glu Gly Gln Thr Leu Asp Leu Asn Cys Val Val Pro Gly Gln Ser 2355 2360 2365 His Ala Gln Val Thr Trp His Lys Arg Gly Gly Ser Leu Pro Val Arg 2370 2375 2380 His Gln Thr His Gly Ser Leu Leu Arg Leu Tyr Gln Ala Ser Pro Ala 2385 2390 2395 2400 Asp Ser Gly Glu Tyr Val Cys Arg Val Leu Gly Ser Ser Val Pro Leu 2405 2410 2415 Glu Ala Ser Val Leu Val Thr Ile Glu Pro Ala Gly Ser Val Pro Ala 2420 2425 2430 Leu Gly Val Thr Pro Thr Val Arg Ile Glu Ser Ser Ser Ser Gln Val 2435 2440 2445 Ala Glu Gly Gln Thr Leu Asp Leu Asn Cys Leu Val Ala Gly Gln Ala 2450 2455 2460 His Ala Gln Val Thr Trp His Lys Arg Gly Gly Ser Leu Pro Ala Arg 2465 2470 2475 2480 His Gln Val His Gly Ser Arg Leu Arg Leu Leu Gln Val Thr Pro Ala 2485 2490 2495 Asp Ser Gly Glu Tyr Val Cys Arg Val Val Gly Ser Ser Gly Thr Gln 2500 2505 2510 Glu Ala Ser Val Leu Val Thr Ile Gln Gln Arg Leu Ser Gly Ser His 2515 2520 2525 Ser Gln Gly Val Ala Tyr Pro Val Arg Ile Glu Ser Ser Ser Ala Ser 2530 2535 2540 Leu Ala Asn Gly His Thr Leu Asp Leu Asn Cys Leu Val Ala Ser Gln 2545 2550 2555 2560 Ala Pro His Thr Ile Thr Trp Tyr Lys Arg Gly Gly Ser Leu Pro Ser 2565 2570 2575 Arg His Gln Ile Val Gly Ser Arg Leu Arg Ile Pro Gln Val Thr Pro 2580 2585 2590 Ala Asp Ser Gly Glu Tyr Val Cys His Val Ser Asn Gly Ala Gly Ser 2595 2600 2605 Arg Glu Thr Ser Leu Ile Val Thr Ile Gln Gly Ser Gly Ser Ser His 2610 2615 2620 Val Pro Ser Val Ser Pro Pro Ile Arg Ile Glu Ser Ser Ser Pro Thr 2625 2630 2635 2640 Val Val Glu Gly Gln Thr Leu Asp Leu Asn Cys Val Val Ala Arg Gln 2645 2650 2655 Pro Gln Ala Ile Ile Thr Trp Tyr Lys Arg Gly Gly Ser Leu Pro Ser 2660 2665 2670 Arg His Gln Thr His Gly Ser His Leu Arg Leu His Gln Met Ser Val 2675 2680 2685 Ala Asp Ser Gly Glu Tyr Val Cys Arg Ala Asn Asn Asn Ile Asp Ala 2690 2695 2700 Leu Glu Ala Ser Ile Val Ile Ser Val Ser Pro Ser Ala Gly Ser Pro 2705 2710 2715 2720 Ser Ala Pro Gly Ser Ser Met Pro Ile Arg Ile Glu Ser Ser Ser Ser 2725 2730 2735 His Val Ala Glu Gly Glu Thr Leu Asp Leu Asn Cys Val Val Pro Gly 2740 2745 2750 Gln Ala His Ala Gln Val Thr Trp His Lys Arg Gly Gly Ser Leu Pro 2755 2760 2765 Ser His His Gln Thr Arg Gly Ser Arg Leu Arg Leu His His Val Ser 2770 2775 2780 Pro Ala Asp Ser Gly Glu Tyr Val Cys Arg Val Met Gly Ser Ser Gly 2785 2790 2795 2800 Pro Leu Glu Ala Ser Val Leu Val Thr Ile Glu Ala Ser Gly Ser Ser 2805 2810 2815 Ala Val His Val Pro Ala Pro Gly Gly Ala Pro Pro Ile Arg Ile Glu 2820 2825 2830 Pro Ser Ser Ser Arg Val Ala Glu Gly Gln Thr Leu Asp Leu Lys Cys 2835 2840 2845 Val Val Pro Gly Gln Ala His Ala Gln Val Thr Trp His Lys Arg Gly 2850 2855 2860 Gly Asn Leu Pro Ala Arg His Gln Val His Gly Pro Leu Leu Arg Leu 2865 2870 2875 2880 Asn Gln Val Ser Pro Ala Asp Ser Gly Glu Tyr Ser Cys Gln Val Thr 2885 2890 2895 Gly Ser Ser Gly Thr Leu Glu Ala Ser Val Leu Val Thr Ile Glu Pro 2900 2905 2910 Ser Ser Pro Gly Pro Ile Pro Ala Pro Gly Leu Ala Gln Pro Ile Tyr 2915 2920 2925 Ile Glu Ala Ser Ser Ser His Val Thr Glu Gly Gln Thr Leu Asp Leu 2930 2935 2940 Asn Cys Val Val Pro Gly Gln Ala His Ala Gln Val Thr Trp Tyr Lys 2945 2950 2955 2960 Arg Gly Gly Ser Leu Pro Ala Arg His Gln Thr His Gly Ser Gln Leu 2965 2970 2975 Arg Leu His Leu Val Ser Pro Ala Asp Ser Gly Glu Tyr Val Cys Arg 2980 2985 2990 Ala Ala Ser Gly Pro Gly Pro Glu Gln Glu Ala Ser Phe Thr Val Thr 2995 3000 3005 Val Pro Pro Ser Glu Gly Ser Ser Tyr Arg Leu Arg Ser Pro Val Ile 3010 3015 3020 Ser Ile Asp Pro Pro Ser Ser Thr Val Gln Gln Gly Gln Asp Ala Ser 3025 3030 3035 3040 Phe Lys Cys Leu Ile His Asp Gly Ala Ala Pro Ile Ser Leu Glu Trp 3045 3050 3055 Lys Thr Arg Asn Gln Glu Leu Glu Asp Asn Val His Ile Ser Pro Asn 3060 3065 3070 Gly Ser Ile Ile Thr Ile Val Gly Thr Arg Pro Ser Asn His Gly Thr 3075 3080 3085 Tyr Arg Cys Val Ala Ser Asn Ala Tyr Gly Val Ala Gln Ser Val Val 3090 3095 3100 Asn Leu Ser Val His Gly Pro Pro Thr Val Ser Val Leu Pro Glu Gly 3105 3110 3115 3120 Pro Val Trp Val Lys Val Gly Lys Ala Val Thr Leu Glu Cys Val Ser 3125 3130 3135 Ala Gly Glu Pro Arg Ser Ser Ala Arg Trp Thr Arg Ile Ser Ser Thr 3140 3145 3150 Pro Ala Lys Leu Glu Gln Arg Thr Tyr Gly Leu Met Asp Ser His Ala 3155 3160 3165 Val Leu Gln Ile Ser Ser Ala Lys Pro Ser Asp Ala Gly Thr Tyr Val 3170 3175 3180 Cys Leu Ala Gln Asn Ala Leu Gly Thr Ala Gln Lys Gln Val Glu Val 3185 3190 3195 3200 Ile Val Asp Thr Gly Ala Met Ala Pro Gly Ala Pro Gln Val Gln Ala 3205 3210 3215 Glu Glu Ala Glu Leu Thr Val Glu Ala Gly His Thr Ala Thr Leu Arg 3220 3225 3230 Cys Ser Ala Thr Gly Ser Pro Ala Pro Thr Ile His Trp Ser Lys Leu 3235 3240 3245 Arg Ser Pro Leu Pro Trp Gln His Arg Leu Glu Gly Asp Thr Leu Ile 3250 3255 3260 Ile Pro Arg Val Ala Gln Gln Asp Ser Gly Gln Tyr Ile Cys Asn Ala 3265 3270 3275 3280 Thr Ser Pro Ala Gly His Ala Glu Ala Thr Ile Ile Leu His Val Glu 3285 3290 3295 Ser Pro Pro Tyr Ala Thr Thr Val Pro Glu His Ala Ser Val Gln Ala 3300 3305 3310 Gly Glu Thr Val Gln Leu Gln Cys Leu Ala His Gly Thr Pro Pro Leu 3315 3320 3325 Thr Phe Gln Trp Ser Arg Val Gly Ser Ser Leu Pro Gly Arg Ala Thr 3330 3335 3340 Ala Arg Asn Glu Leu Leu His Phe Glu Arg Ala Ala Pro Glu Asp Ser 3345 3350 3355 3360 Gly Arg Tyr Arg Cys Arg Val Thr Asn Lys Val Gly Ser Ala Glu Ala 3365 3370 3375 Phe Ala Gln Leu Leu Val Gln Gly Pro Pro Gly Ser Leu Pro Ala Thr 3380 3385 3390 Ser Ile Pro Ala Gly Ser Thr Pro Thr Val Gln Val Thr Pro Gln Leu 3395 3400 3405 Glu Thr Lys Ser Ile Gly Ala Ser Val Glu Phe His Cys Ala Val Pro 3410 3415 3420 Ser Asp Arg Gly Thr Gln Leu Arg Trp Phe Lys Glu Gly Gly Gln Leu 3425 3430 3435 3440 Pro Pro Gly His Ser Val Gln Asp Gly Val Leu Arg Ile Gln Asn Leu 3445 3450 3455 Asp Gln Ser Cys Gln Gly Thr Tyr Ile Cys Gln Ala His Gly Pro Trp 3460 3465 3470 Gly Lys Ala Gln Ala Ser Ala Gln Leu Val Ile Gln Ala Leu Pro Ser 3475 3480 3485 Val Leu Ile Asn Ile Arg Thr Ser Val Gln Thr Val Val Val Gly His 3490 3495 3500 Ala Val Glu Phe Glu Cys Leu Ala Leu Gly Asp Pro Lys Pro Gln Val 3505 3510 3515 3520 Thr Trp Ser Lys Val Gly Gly His Leu Arg Pro Gly Ile Val Gln Ser 3525 3530 3535 Gly Gly Val Val Arg Ile Ala His Val Glu Leu Ala Asp Ala Gly Gln 3540 3545 3550 Tyr Arg Cys Thr Ala Thr Asn Ala Ala Gly Thr Thr Gln Ser His Val 3555 3560 3565 Leu Leu Leu Val Gln Ala Leu Pro Gln Ile Ser Met Pro Gln Glu Val 3570 3575 3580 Arg Val Pro Ala Gly Ser Ala Ala Val Phe Pro Cys Ile Ala Ser Gly 3585 3590 3595 3600 Tyr Pro Thr Pro Asp Ile Ser Trp Ser Lys Leu Asp Gly Ser Leu Pro 3605 3610 3615 Pro Asp Ser Arg Leu Glu Asn Asn Met Leu Met Leu Pro Ser Val Arg 3620 3625 3630 Pro Gln Asp Ala Gly Thr Tyr Val Cys Thr Ala Thr Asn Arg Gln Gly 3635 3640 3645 Lys Val Lys Ala Phe Ala His Leu Gln Val Pro Glu Arg Val Val Pro 3650 3655 3660 Tyr Phe Thr Gln Thr Pro Tyr Ser Phe Leu Pro Leu Pro Thr Ile Lys 3665 3670 3675 3680 Asp Ala Tyr Arg Lys Phe Glu Ile Lys Ile Thr Phe Arg Pro Asp Ser 3685 3690 3695 Ala Asp Gly Met Leu Leu Tyr Asn Gly Gln Lys Arg Val Pro Gly Ser 3700 3705 3710 Pro Thr Asn Leu Ala Asn Arg Gln Pro Asp Phe Ile Ser Phe Gly Leu 3715 3720 3725 Val Gly Gly Arg Pro Glu Phe Arg Phe Asp Ala Gly Ser Gly Met Ala 3730 3735 3740 Thr Ile Arg His Pro Thr Pro Leu Ala Leu Gly His Phe His Thr Val 3745 3750 3755 3760 Thr Leu Leu Arg Ser Leu Thr Gln Gly Ser Leu Ile Val Gly Asp Leu 3765 3770 3775 Ala Pro Val Asn Gly Thr Ser Gln Gly Lys Phe Gln Gly Leu Asp Leu 3780 3785 3790 Asn Glu Glu Leu Tyr Leu Gly Gly Tyr Pro Asp Tyr Gly Ala Ile Pro 3795 3800 3805 Lys Ala Gly Leu Ser Ser Gly Phe Ile Gly Cys Val Arg Glu Leu Arg 3810 3815 3820 Ile Gln Gly Glu Glu Ile Val Phe His Asp Leu Asn Leu Thr Ala His 3825 3830 3835 3840 Gly Ile Ser His Cys Pro Thr Cys Arg Asp Arg Pro Cys Gln Asn Gly 3845 3850 3855 Gly Gln Cys His Asp Ser Glu Ser Ser Ser Tyr Val Cys Val Cys Pro 3860 3865 3870 Ala Gly Phe Thr Gly Ser Arg Cys Glu His Ser Gln Ala Leu His Cys 3875 3880 3885 His Pro Glu Ala Cys Gly Pro Asp Ala Thr Cys Val Asn Arg Pro Asp 3890 3895 3900 Gly Arg Gly Tyr Thr Cys Arg Cys His Leu Gly Arg Ser Gly Leu Arg 3905 3910 3915 3920 Cys Glu Glu Gly Val Thr Val Thr Thr Pro Ser Leu Ser Gly Ala Gly 3925 3930 3935 Ser Tyr Leu Ala Leu Pro Ala Leu Thr Asn Thr His His Glu Leu Arg 3940 3945 3950 Leu Asp Val Glu Phe Lys Pro Leu Ala Pro Asp Gly Val Leu Leu Phe 3955 3960 3965 Ser Gly Gly Lys Ser Gly Pro Val Glu Asp Phe Val Ser Leu Ala Met 3970 3975 3980 Val Gly Gly His Leu Glu Phe Arg Tyr Glu Leu Gly Ser Gly Leu Ala 3985 3990 3995 4000 Val Leu Arg Ser Ala Glu Pro Leu Ala Leu Gly Arg Trp His Arg Val 4005 4010 4015 Ser Ala Glu Arg Leu Asn Lys Asp Gly Ser Leu Arg Val Asn Gly Gly 4020 4025 4030 Arg Pro Val Leu Arg Ser Ser Pro Gly Lys Ser Gln Gly Leu Asn Leu 4035 4040 4045 His Thr Leu Leu Tyr Leu Gly Gly Val Glu Pro Ser Val Pro Leu Ser 4050 4055 4060 Pro Ala Thr Asn Met Ser Ala His Phe Arg Gly Cys Val Gly Glu Val 4065 4070 4075 4080 Ser Val Asn Gly Lys Arg Leu Asp Leu Thr Tyr Ser Phe Leu Gly Ser 4085 4090 4095 Gln Gly Ile Gly Gln Cys Tyr Asp Ser Ser Pro Cys Glu Arg Gln Pro 4100 4105 4110 Cys Gln His Gly Ala Thr Cys Met Pro Ala Gly Glu Tyr Glu Phe Gln 4115 4120 4125 Cys Leu Cys Arg Asp Gly Phe Lys Gly Asp Leu Cys Glu His Glu Glu 4130 4135 4140 Asn Pro Cys Gln Leu Arg Glu Pro Cys Leu His Gly Gly Thr Cys Gln 4145 4150 4155 4160 Gly Thr Arg Cys Leu Cys Leu Pro Gly Phe Ser Gly Pro Arg Cys Gln 4165 4170 4175 Gln Gly Ser Gly His Gly Ile Ala Glu Ser Asp Trp His Leu Glu Gly 4180 4185 4190 Ser Gly Gly Asn Asp Ala Pro Gly Gln Tyr Gly Ala Tyr Phe His Asp 4195 4200 4205 Asp Gly Phe Leu Ala Phe Pro Gly His Val Phe Ser Arg Ser Leu Pro 4210 4215 4220 Glu Val Pro Glu Thr Ile Glu Leu Glu Val Arg Thr Ser Thr Ala Ser 4225 4230 4235 4240 Gly Leu Leu Leu Trp Gln Gly Val Glu Val Gly Glu Ala Gly Gln Gly 4245 4250 4255 Lys Asp Phe Ile Ser Leu Gly Leu Gln Asp Gly His Leu Val Phe Arg 4260 4265 4270 Tyr Gln Leu Gly Ser Gly Glu Ala Arg Leu Val Ser Glu Asp Pro Ile 4275 4280 4285 Asn Asp Gly Glu Trp His Arg Val Thr Ala Leu Arg Glu Gly Arg Arg 4290 4295 4300 Gly Ser Ile Gln Val Asp Gly Glu Glu Leu Val Ser Gly Arg Ser Pro 4305 4310 4315 4320 Gly Pro Asn Val Ala Val Asn Ala Lys Gly Ser Val Tyr Ile Gly Gly 4325 4330 4335 Ala Pro Asp Val Ala Thr Leu Thr Gly Gly Arg Phe Ser Ser Gly Ile 4340 4345 4350 Thr Gly Cys Val Lys Asn Leu Val Leu His Ser Ala Arg Pro Gly Ala 4355 4360 4365 Pro Pro Pro Gln Pro Leu Asp Leu Gln His Arg Ala Gln Ala Gly Ala 4370 4375 4380 Asn Thr Arg Pro Cys Pro Ser 4385 4390 <210> SEQ ID NO 90 <211> LENGTH: 198 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 90 Met Asp Ser Leu Leu Met Asn Arg Arg Lys Phe Leu Tyr Gln Phe Lys 1 5 10 15 Asn Val Arg Trp Ala Lys Gly Arg Arg Glu Thr Tyr Leu Cys Tyr Val 20 25 30 Val Lys Arg Arg Asp Ser Ala Thr Ser Phe Ser Leu Asp Phe Gly Tyr 35 40 45 Leu Arg Asn Lys Asn Gly Cys His Val Glu Leu Leu Phe Leu Arg Tyr 50 55 60 Ile Ser Asp Trp Asp Leu Asp Pro Gly Arg Cys Tyr Arg Val Thr Trp 65 70 75 80 Phe Thr Ser Trp Ser Pro Cys Tyr Asp Cys Ala Arg His Val Ala Asp 85 90 95 Phe Leu Arg Gly Asn Pro Asn Leu Ser Leu Arg Ile Phe Thr Ala Arg 100 105 110 Leu Tyr Phe Cys Glu Asp Arg Lys Ala Glu Pro Glu Gly Leu Arg Arg 115 120 125 Leu His Arg Ala Gly Val Gln Ile Ala Ile Met Thr Phe Lys Asp Tyr 130 135 140 Phe Tyr Cys Trp Asn Thr Phe Val Glu Asn His Glu Arg Thr Phe Lys 145 150 155 160 Ala Trp Glu Gly Leu His Glu Asn Ser Val Arg Leu Ser Arg Gln Leu 165 170 175 Arg Arg Ile Leu Leu Pro Leu Tyr Glu Val Asp Asp Leu Arg Asp Ala 180 185 190 Phe Arg Thr Leu Gly Leu 195 <210> SEQ ID NO 91 <211> LENGTH: 491 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 91 Met Glu Leu Ser Val Leu Leu Phe Leu Ala Leu Leu Thr Gly Leu Leu 1 5 10 15 Leu Leu Leu Val Gln Arg His Pro Asn Thr His Asp Arg Leu Pro Pro 20 25 30 Gly Pro Arg Pro Leu Pro Leu Leu Gly Asn Leu Leu Gln Met Asp Arg 35 40 45 Arg Gly Leu Leu Lys Ser Phe Leu Arg Phe Arg Glu Lys Tyr Gly Asp 50 55 60 Val Phe Thr Val His Leu Gly Pro Arg Pro Val Val Met Leu Cys Gly 65 70 75 80 Val Glu Ala Ile Arg Glu Ala Leu Val Asp Lys Ala Glu Ala Phe Ser 85 90 95 Gly Arg Gly Lys Ile Ala Met Val Asp Pro Phe Phe Arg Gly Tyr Gly 100 105 110 Val Ile Phe Ala Asn Gly Asn Arg Trp Lys Val Leu Arg Arg Phe Ser 115 120 125 Val Thr Thr Met Arg Asp Phe Gly Met Gly Lys Arg Ser Val Glu Glu 130 135 140 Arg Ile Gln Glu Glu Ala Gln Cys Leu Ile Glu Glu Leu Arg Lys Ser 145 150 155 160 Lys Gly Ala Leu Met Asp Pro Thr Phe Leu Phe Gln Ser Ile Thr Ala 165 170 175 Asn Ile Ile Cys Ser Ile Val Phe Gly Lys Arg Phe His Tyr Gln Asp 180 185 190 Gln Glu Phe Leu Lys Met Leu Asn Leu Phe Tyr Gln Thr Phe Ser Leu 195 200 205 Ile Ser Ser Val Phe Gly Gln Leu Phe Glu Leu Phe Ser Gly Phe Leu 210 215 220 Lys Tyr Phe Pro Gly Ala His Arg Gln Val Tyr Lys Asn Leu Gln Glu 225 230 235 240 Ile Asn Ala Tyr Ile Gly His Ser Val Glu Lys His Arg Glu Thr Leu 245 250 255 Asp Pro Ser Ala Pro Lys Asp Leu Ile Asp Thr Tyr Leu Leu His Met 260 265 270 Glu Lys Glu Lys Ser Asn Ala His Ser Glu Phe Ser His Gln Asn Leu 275 280 285 Asn Leu Asn Thr Leu Ser Leu Phe Phe Ala Gly Thr Glu Thr Thr Ser 290 295 300 Thr Thr Leu Arg Tyr Gly Phe Leu Leu Met Leu Lys Tyr Pro His Val 305 310 315 320 Ala Glu Arg Val Tyr Arg Glu Ile Glu Gln Val Ile Gly Pro His Arg 325 330 335 Pro Pro Glu Leu His Asp Arg Ala Lys Met Pro Tyr Thr Glu Ala Val 340 345 350 Ile Tyr Glu Ile Gln Arg Phe Ser Asp Leu Leu Pro Met Gly Val Pro 355 360 365 His Ile Val Thr Gln His Thr Ser Phe Arg Gly Tyr Ile Ile Pro Lys 370 375 380 Asp Thr Glu Val Phe Leu Ile Leu Ser Thr Ala Leu His Asp Pro His 385 390 395 400 Tyr Phe Glu Lys Pro Asp Ala Phe Asn Pro Asp His Phe Leu Asp Ala 405 410 415 Asn Gly Ala Leu Lys Lys Thr Glu Ala Phe Ile Pro Phe Ser Leu Gly 420 425 430 Lys Arg Ile Cys Leu Gly Glu Gly Ile Ala Arg Ala Glu Leu Phe Leu 435 440 445 Phe Phe Thr Thr Ile Leu Gln Asn Phe Ser Met Ala Ser Pro Val Ala 450 455 460 Pro Glu Asp Ile Asp Leu Thr Pro Gln Glu Cys Gly Val Gly Lys Ile 465 470 475 480 Pro Pro Thr Tyr Gln Ile Arg Phe Leu Pro Arg 485 490 <210> SEQ ID NO 92 <211> LENGTH: 454 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 92 Met Asp Phe Phe Arg Val Val Glu Asn Gln Gln Pro Pro Ala Thr Met 1 5 10 15 Pro Leu Asn Val Ser Phe Thr Asn Arg Asn Tyr Asp Leu Asp Tyr Asp 20 25 30 Ser Val Gln Pro Tyr Phe Tyr Cys Asp Glu Glu Glu Asn Phe Tyr Gln 35 40 45 Gln Gln Gln Gln Ser Glu Leu Gln Pro Pro Ala Pro Ser Glu Asp Ile 50 55 60 Trp Lys Lys Phe Glu Leu Leu Pro Thr Pro Pro Leu Ser Pro Ser Arg 65 70 75 80 Arg Ser Gly Leu Cys Ser Pro Ser Tyr Val Ala Val Thr Pro Phe Ser 85 90 95 Leu Arg Gly Asp Asn Asp Gly Gly Gly Gly Ser Phe Ser Thr Ala Asp 100 105 110 Gln Leu Glu Met Val Thr Glu Leu Leu Gly Gly Asp Met Val Asn Gln 115 120 125 Ser Phe Ile Cys Asp Pro Asp Asp Glu Thr Phe Ile Lys Asn Ile Ile 130 135 140 Ile Gln Asp Cys Met Trp Ser Gly Phe Ser Ala Ala Ala Lys Leu Val 145 150 155 160 Ser Glu Lys Leu Ala Ser Tyr Gln Ala Ala Arg Lys Asp Ser Gly Ser 165 170 175 Pro Asn Pro Ala Arg Gly His Ser Val Cys Ser Thr Ser Ser Leu Tyr 180 185 190 Leu Gln Asp Leu Ser Ala Ala Ala Ser Glu Cys Ile Asp Pro Ser Val 195 200 205 Val Phe Pro Tyr Pro Leu Asn Asp Ser Ser Ser Pro Lys Ser Cys Ala 210 215 220 Ser Gln Asp Ser Ser Ala Phe Ser Pro Ser Ser Asp Ser Leu Leu Ser 225 230 235 240 Ser Thr Glu Ser Ser Pro Gln Gly Ser Pro Glu Pro Leu Val Leu His 245 250 255 Glu Glu Thr Pro Pro Thr Thr Ser Ser Asp Ser Glu Glu Glu Gln Glu 260 265 270 Asp Glu Glu Glu Ile Asp Val Val Ser Val Glu Lys Arg Gln Ala Pro 275 280 285 Gly Lys Arg Ser Glu Ser Gly Ser Pro Ser Ala Gly Gly His Ser Lys 290 295 300 Pro Pro His Ser Pro Leu Val Leu Lys Arg Cys His Val Ser Thr His 305 310 315 320 Gln His Asn Tyr Ala Ala Pro Pro Ser Thr Arg Lys Asp Tyr Pro Ala 325 330 335 Ala Lys Arg Val Lys Leu Asp Ser Val Arg Val Leu Arg Gln Ile Ser 340 345 350 Asn Asn Arg Lys Cys Thr Ser Pro Arg Ser Ser Asp Thr Glu Glu Asn 355 360 365 Val Lys Arg Arg Thr His Asn Val Leu Glu Arg Gln Arg Arg Asn Glu 370 375 380 Leu Lys Arg Ser Phe Phe Ala Leu Arg Asp Gln Ile Pro Glu Leu Glu 385 390 395 400 Asn Asn Glu Lys Ala Pro Lys Val Val Ile Leu Lys Lys Ala Thr Ala 405 410 415 Tyr Ile Leu Ser Val Gln Ala Glu Glu Gln Lys Leu Ile Ser Glu Glu 420 425 430 Asp Leu Leu Arg Lys Arg Arg Glu Gln Leu Lys His Lys Leu Glu Gln 435 440 445 Leu Arg Asn Ser Cys Ala 450 <210> SEQ ID NO 93 <211> LENGTH: 894 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 93 Met Ile Leu Leu Ala Val Leu Phe Leu Cys Phe Ile Ser Ser Tyr Ser 1 5 10 15 Ala Ser Val Lys Gly His Thr Thr Gly Leu Ser Leu Asn Asn Asp Arg 20 25 30 Leu Tyr Lys Leu Thr Tyr Ser Thr Glu Val Leu Leu Asp Arg Gly Lys 35 40 45 Gly Lys Leu Gln Asp Ser Val Gly Tyr Arg Ile Ser Ser Asn Val Asp 50 55 60 Val Ala Leu Leu Trp Arg Asn Pro Asp Gly Asp Asp Asp Gln Leu Ile 65 70 75 80 Gln Ile Thr Met Lys Asp Val Asn Val Glu Asn Val Asn Gln Gln Arg 85 90 95 Gly Glu Lys Ser Ile Phe Lys Gly Lys Ser Pro Ser Lys Ile Met Gly 100 105 110 Lys Glu Asn Leu Glu Ala Leu Gln Arg Pro Thr Leu Leu His Leu Ile 115 120 125 His Gly Lys Val Lys Glu Phe Tyr Ser Tyr Gln Asn Glu Ala Val Ala 130 135 140 Ile Glu Asn Ile Lys Arg Gly Leu Ala Ser Leu Phe Gln Thr Gln Leu 145 150 155 160 Ser Ser Gly Thr Thr Asn Glu Val Asp Ile Ser Gly Asn Cys Lys Val 165 170 175 Thr Tyr Gln Ala His Gln Asp Lys Val Ile Lys Ile Lys Ala Leu Asp 180 185 190 Ser Cys Lys Ile Ala Arg Ser Gly Phe Thr Thr Pro Asn Gln Val Leu 195 200 205 Gly Val Ser Ser Lys Ala Thr Ser Val Thr Thr Tyr Lys Ile Glu Asp 210 215 220 Ser Phe Val Ile Ala Val Leu Ala Glu Glu Thr His Asn Phe Gly Leu 225 230 235 240 Asn Phe Leu Gln Thr Ile Lys Gly Lys Ile Val Ser Lys Gln Lys Leu 245 250 255 Glu Leu Lys Thr Thr Glu Ala Gly Pro Arg Leu Met Ser Gly Lys Gln 260 265 270 Ala Ala Ala Ile Ile Lys Ala Val Asp Ser Lys Tyr Thr Ala Ile Pro 275 280 285 Ile Val Gly Gln Val Phe Gln Ser His Cys Lys Gly Cys Pro Ser Leu 290 295 300 Ser Glu Leu Trp Arg Ser Thr Arg Lys Tyr Leu Gln Pro Asp Asn Leu 305 310 315 320 Ser Lys Ala Glu Ala Val Arg Asn Phe Leu Ala Phe Ile Gln His Leu 325 330 335 Arg Thr Ala Lys Lys Glu Glu Ile Leu Gln Ile Leu Lys Met Glu Asn 340 345 350 Lys Glu Val Leu Pro Gln Leu Val Asp Ala Val Thr Ser Ala Gln Thr 355 360 365 Ser Asp Ser Leu Glu Ala Ile Leu Asp Phe Leu Asp Phe Lys Ser Asp 370 375 380 Ser Ser Ile Ile Leu Gln Glu Arg Phe Leu Tyr Ala Cys Gly Phe Ala 385 390 395 400 Ser His Pro Asn Glu Glu Leu Leu Arg Ala Leu Ile Ser Lys Phe Lys 405 410 415 Gly Ser Ile Gly Ser Ser Asp Ile Arg Glu Thr Val Met Ile Ile Thr 420 425 430 Gly Thr Leu Val Arg Lys Leu Cys Gln Asn Glu Gly Cys Lys Leu Lys 435 440 445 Ala Val Val Glu Ala Lys Lys Leu Ile Leu Gly Gly Leu Glu Lys Ala 450 455 460 Glu Lys Lys Glu Asp Thr Arg Met Tyr Leu Leu Ala Leu Lys Asn Ala 465 470 475 480 Leu Leu Pro Glu Gly Ile Pro Ser Leu Leu Lys Tyr Ala Glu Ala Gly 485 490 495 Glu Gly Pro Ile Ser His Leu Ala Thr Thr Ala Leu Gln Arg Tyr Asp 500 505 510 Leu Pro Phe Ile Thr Asp Glu Val Lys Lys Thr Leu Asn Arg Ile Tyr 515 520 525 His Gln Asn Arg Lys Val His Glu Lys Thr Val Arg Thr Ala Ala Ala 530 535 540 Ala Ile Ile Leu Asn Asn Asn Pro Ser Tyr Met Asp Val Lys Asn Ile 545 550 555 560 Leu Leu Ser Ile Gly Glu Leu Pro Gln Glu Met Asn Lys Tyr Met Leu 565 570 575 Ala Ile Val Gln Asp Ile Leu Arg Phe Glu Met Pro Ala Ser Lys Ile 580 585 590 Val Arg Arg Val Leu Lys Glu Met Val Ala His Asn Tyr Asp Arg Phe 595 600 605 Ser Arg Ser Gly Ser Ser Ser Ala Tyr Thr Gly Tyr Ile Glu Arg Ser 610 615 620 Pro Arg Ser Ala Ser Thr Tyr Ser Leu Asp Ile Leu Tyr Ser Gly Ser 625 630 635 640 Gly Ile Leu Arg Arg Ser Asn Leu Asn Ile Phe Gln Tyr Ile Gly Lys 645 650 655 Ala Gly Leu His Gly Ser Gln Val Val Ile Glu Ala Gln Gly Leu Glu 660 665 670 Ala Leu Ile Ala Ala Thr Pro Asp Glu Gly Glu Glu Asn Leu Asp Ser 675 680 685 Tyr Ala Gly Met Ser Ala Ile Leu Phe Asp Val Gln Leu Arg Pro Val 690 695 700 Thr Phe Phe Asn Gly Tyr Ser Asp Leu Met Ser Lys Met Leu Ser Ala 705 710 715 720 Ser Gly Asp Pro Ile Ser Val Val Lys Gly Leu Ile Leu Leu Ile Asp 725 730 735 His Ser Gln Glu Leu Gln Leu Gln Ser Gly Leu Lys Ala Asn Ile Glu 740 745 750 Val Gln Gly Gly Leu Ala Ile Asp Ile Ser Gly Ala Met Glu Phe Ser 755 760 765 Leu Trp Tyr Arg Glu Ser Lys Thr Arg Val Lys Asn Arg Val Thr Val 770 775 780 Val Ile Thr Thr Asp Ile Thr Val Asp Ser Ser Phe Val Lys Ala Gly 785 790 795 800 Leu Glu Thr Ser Thr Glu Thr Glu Ala Gly Leu Glu Phe Ile Ser Thr 805 810 815 Val Gln Phe Ser Gln Tyr Pro Phe Leu Val Cys Met Gln Met Asp Lys 820 825 830 Asp Glu Ala Pro Phe Arg Gln Phe Glu Lys Lys Tyr Glu Arg Leu Ser 835 840 845 Thr Gly Arg Gly Tyr Val Ser Gln Lys Arg Lys Glu Ser Val Leu Ala 850 855 860 Gly Cys Glu Phe Pro Leu His Gln Glu Asn Ser Glu Met Cys Lys Val 865 870 875 880 Val Phe Ala Pro Gln Pro Asp Ser Thr Ser Ser Gly Trp Phe 885 890 <210> SEQ ID NO 94 <211> LENGTH: 1210 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 94 Met Arg Pro Ser Gly Thr Ala Gly Ala Ala Leu Leu Ala Leu Leu Ala 1 5 10 15 Ala Leu Cys Pro Ala Ser Arg Ala Leu Glu Glu Lys Lys Val Cys Gln 20 25 30 Gly Thr Ser Asn Lys Leu Thr Gln Leu Gly Thr Phe Glu Asp His Phe 35 40 45 Leu Ser Leu Gln Arg Met Phe Asn Asn Cys Glu Val Val Leu Gly Asn 50 55 60 Leu Glu Ile Thr Tyr Val Gln Arg Asn Tyr Asp Leu Ser Phe Leu Lys 65 70 75 80 Thr Ile Gln Glu Val Ala Gly Tyr Val Leu Ile Ala Leu Asn Thr Val 85 90 95 Glu Arg Ile Pro Leu Glu Asn Leu Gln Ile Ile Arg Gly Asn Met Tyr 100 105 110 Tyr Glu Asn Ser Tyr Ala Leu Ala Val Leu Ser Asn Tyr Asp Ala Asn 115 120 125 Lys Thr Gly Leu Lys Glu Leu Pro Met Arg Asn Leu Gln Glu Ile Leu 130 135 140 His Gly Ala Val Arg Phe Ser Asn Asn Pro Ala Leu Cys Asn Val Glu 145 150 155 160 Ser Ile Gln Trp Arg Asp Ile Val Ser Ser Asp Phe Leu Ser Asn Met 165 170 175 Ser Met Asp Phe Gln Asn His Leu Gly Ser Cys Gln Lys Cys Asp Pro 180 185 190 Ser Cys Pro Asn Gly Ser Cys Trp Gly Ala Gly Glu Glu Asn Cys Gln 195 200 205 Lys Leu Thr Lys Ile Ile Cys Ala Gln Gln Cys Ser Gly Arg Cys Arg 210 215 220 Gly Lys Ser Pro Ser Asp Cys Cys His Asn Gln Cys Ala Ala Gly Cys 225 230 235 240 Thr Gly Pro Arg Glu Ser Asp Cys Leu Val Cys Arg Lys Phe Arg Asp 245 250 255 Glu Ala Thr Cys Lys Asp Thr Cys Pro Pro Leu Met Leu Tyr Asn Pro 260 265 270 Thr Thr Tyr Gln Met Asp Val Asn Pro Glu Gly Lys Tyr Ser Phe Gly 275 280 285 Ala Thr Cys Val Lys Lys Cys Pro Arg Asn Tyr Val Val Thr Asp His 290 295 300 Gly Ser Cys Val Arg Ala Cys Gly Ala Asp Ser Tyr Glu Met Glu Glu 305 310 315 320 Asp Gly Val Arg Lys Cys Lys Lys Cys Glu Gly Pro Cys Arg Lys Val 325 330 335 Cys Asn Gly Ile Gly Ile Gly Glu Phe Lys Asp Ser Leu Ser Ile Asn 340 345 350 Ala Thr Asn Ile Lys His Phe Lys Asn Cys Thr Ser Ile Ser Gly Asp 355 360 365 Leu His Ile Leu Pro Val Ala Phe Arg Gly Asp Ser Phe Thr His Thr 370 375 380 Pro Pro Leu Asp Pro Gln Glu Leu Asp Ile Leu Lys Thr Val Lys Glu 385 390 395 400 Ile Thr Gly Phe Leu Leu Ile Gln Ala Trp Pro Glu Asn Arg Thr Asp 405 410 415 Leu His Ala Phe Glu Asn Leu Glu Ile Ile Arg Gly Arg Thr Lys Gln 420 425 430 His Gly Gln Phe Ser Leu Ala Val Val Ser Leu Asn Ile Thr Ser Leu 435 440 445 Gly Leu Arg Ser Leu Lys Glu Ile Ser Asp Gly Asp Val Ile Ile Ser 450 455 460 Gly Asn Lys Asn Leu Cys Tyr Ala Asn Thr Ile Asn Trp Lys Lys Leu 465 470 475 480 Phe Gly Thr Ser Gly Gln Lys Thr Lys Ile Ile Ser Asn Arg Gly Glu 485 490 495 Asn Ser Cys Lys Ala Thr Gly Gln Val Cys His Ala Leu Cys Ser Pro 500 505 510 Glu Gly Cys Trp Gly Pro Glu Pro Arg Asp Cys Val Ser Cys Arg Asn 515 520 525 Val Ser Arg Gly Arg Glu Cys Val Asp Lys Cys Asn Leu Leu Glu Gly 530 535 540 Glu Pro Arg Glu Phe Val Glu Asn Ser Glu Cys Ile Gln Cys His Pro 545 550 555 560 Glu Cys Leu Pro Gln Ala Met Asn Ile Thr Cys Thr Gly Arg Gly Pro 565 570 575 Asp Asn Cys Ile Gln Cys Ala His Tyr Ile Asp Gly Pro His Cys Val 580 585 590 Lys Thr Cys Pro Ala Gly Val Met Gly Glu Asn Asn Thr Leu Val Trp 595 600 605 Lys Tyr Ala Asp Ala Gly His Val Cys His Leu Cys His Pro Asn Cys 610 615 620 Thr Tyr Gly Cys Thr Gly Pro Gly Leu Glu Gly Cys Pro Thr Asn Gly 625 630 635 640 Pro Lys Ile Pro Ser Ile Ala Thr Gly Met Val Gly Ala Leu Leu Leu 645 650 655 Leu Leu Val Val Ala Leu Gly Ile Gly Leu Phe Met Arg Arg Arg His 660 665 670 Ile Val Arg Lys Arg Thr Leu Arg Arg Leu Leu Gln Glu Arg Glu Leu 675 680 685 Val Glu Pro Leu Thr Pro Ser Gly Glu Ala Pro Asn Gln Ala Leu Leu 690 695 700 Arg Ile Leu Lys Glu Thr Glu Phe Lys Lys Ile Lys Val Leu Gly Ser 705 710 715 720 Gly Ala Phe Gly Thr Val Tyr Lys Gly Leu Trp Ile Pro Glu Gly Glu 725 730 735 Lys Val Lys Ile Pro Val Ala Ile Lys Glu Leu Arg Glu Ala Thr Ser 740 745 750 Pro Lys Ala Asn Lys Glu Ile Leu Asp Glu Ala Tyr Val Met Ala Ser 755 760 765 Val Asp Asn Pro His Val Cys Arg Leu Leu Gly Ile Cys Leu Thr Ser 770 775 780 Thr Val Gln Leu Ile Thr Gln Leu Met Pro Phe Gly Cys Leu Leu Asp 785 790 795 800 Tyr Val Arg Glu His Lys Asp Asn Ile Gly Ser Gln Tyr Leu Leu Asn 805 810 815 Trp Cys Val Gln Ile Ala Lys Gly Met Asn Tyr Leu Glu Asp Arg Arg 820 825 830 Leu Val His Arg Asp Leu Ala Ala Arg Asn Val Leu Val Lys Thr Pro 835 840 845 Gln His Val Lys Ile Thr Asp Phe Gly Leu Ala Lys Leu Leu Gly Ala 850 855 860 Glu Glu Lys Glu Tyr His Ala Glu Gly Gly Lys Val Pro Ile Lys Trp 865 870 875 880 Met Ala Leu Glu Ser Ile Leu His Arg Ile Tyr Thr His Gln Ser Asp 885 890 895 Val Trp Ser Tyr Gly Val Thr Val Trp Glu Leu Met Thr Phe Gly Ser 900 905 910 Lys Pro Tyr Asp Gly Ile Pro Ala Ser Glu Ile Ser Ser Ile Leu Glu 915 920 925 Lys Gly Glu Arg Leu Pro Gln Pro Pro Ile Cys Thr Ile Asp Val Tyr 930 935 940 Met Ile Met Val Lys Cys Trp Met Ile Asp Ala Asp Ser Arg Pro Lys 945 950 955 960 Phe Arg Glu Leu Ile Ile Glu Phe Ser Lys Met Ala Arg Asp Pro Gln 965 970 975 Arg Tyr Leu Val Ile Gln Gly Asp Glu Arg Met His Leu Pro Ser Pro 980 985 990 Thr Asp Ser Asn Phe Tyr Arg Ala Leu Met Asp Glu Glu Asp Met Asp 995 1000 1005 Asp Val Val Asp Ala Asp Glu Tyr Leu Ile Pro Gln Gln Gly Phe Phe 1010 1015 1020 Ser Ser Pro Ser Thr Ser Arg Thr Pro Leu Leu Ser Ser Leu Ser Ala 1025 1030 1035 1040 Thr Ser Asn Asn Ser Thr Val Ala Cys Ile Asp Arg Asn Gly Leu Gln 1045 1050 1055 Ser Cys Pro Ile Lys Glu Asp Ser Phe Leu Gln Arg Tyr Ser Ser Asp 1060 1065 1070 Pro Thr Gly Ala Leu Thr Glu Asp Ser Ile Asp Asp Thr Phe Leu Pro 1075 1080 1085 Val Pro Glu Tyr Ile Asn Gln Ser Val Pro Lys Arg Pro Ala Gly Ser 1090 1095 1100 Val Gln Asn Pro Val Tyr His Asn Gln Pro Leu Asn Pro Ala Pro Ser 1105 1110 1115 1120 Arg Asp Pro His Tyr Gln Asp Pro His Ser Thr Ala Val Gly Asn Pro 1125 1130 1135 Glu Tyr Leu Asn Thr Val Gln Pro Thr Cys Val Asn Ser Thr Phe Asp 1140 1145 1150 Ser Pro Ala His Trp Ala Gln Lys Gly Ser His Gln Ile Ser Leu Asp 1155 1160 1165 Asn Pro Asp Tyr Gln Gln Asp Phe Phe Pro Lys Glu Ala Lys Pro Asn 1170 1175 1180 Gly Ile Phe Lys Gly Ser Thr Ala Glu Asn Ala Glu Tyr Leu Arg Val 1185 1190 1195 1200 Ala Pro Gln Ser Ser Glu Phe Ile Gly Ala 1205 1210 <210> SEQ ID NO 95 <211> LENGTH: 705 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 95 Met Arg Pro Ser Gly Thr Ala Gly Ala Ala Leu Leu Ala Leu Leu Ala 1 5 10 15 Ala Leu Cys Pro Ala Ser Arg Ala Leu Glu Glu Lys Lys Val Cys Gln 20 25 30 Gly Thr Ser Asn Lys Leu Thr Gln Leu Gly Thr Phe Glu Asp His Phe 35 40 45 Leu Ser Leu Gln Arg Met Phe Asn Asn Cys Glu Val Val Leu Gly Asn 50 55 60 Leu Glu Ile Thr Tyr Val Gln Arg Asn Tyr Asp Leu Ser Phe Leu Lys 65 70 75 80 Thr Ile Gln Glu Val Ala Gly Tyr Val Leu Ile Ala Leu Asn Thr Val 85 90 95 Glu Arg Ile Pro Leu Glu Asn Leu Gln Ile Ile Arg Gly Asn Met Tyr 100 105 110 Tyr Glu Asn Ser Tyr Ala Leu Ala Val Leu Ser Asn Tyr Asp Ala Asn 115 120 125 Lys Thr Gly Leu Lys Glu Leu Pro Met Arg Asn Leu Gln Glu Ile Leu 130 135 140 His Gly Ala Val Arg Phe Ser Asn Asn Pro Ala Leu Cys Asn Val Glu 145 150 155 160 Ser Ile Gln Trp Arg Asp Ile Val Ser Ser Asp Phe Leu Ser Asn Met 165 170 175 Ser Met Asp Phe Gln Asn His Leu Gly Ser Cys Gln Lys Cys Asp Pro 180 185 190 Ser Cys Pro Asn Gly Ser Cys Trp Gly Ala Gly Glu Glu Asn Cys Gln 195 200 205 Lys Leu Thr Lys Ile Ile Cys Ala Gln Gln Cys Ser Gly Arg Cys Arg 210 215 220 Gly Lys Ser Pro Ser Asp Cys Cys His Asn Gln Cys Ala Ala Gly Cys 225 230 235 240 Thr Gly Pro Arg Glu Ser Asp Cys Leu Val Cys Arg Lys Phe Arg Asp 245 250 255 Glu Ala Thr Cys Lys Asp Thr Cys Pro Pro Leu Met Leu Tyr Asn Pro 260 265 270 Thr Thr Tyr Gln Met Asp Val Asn Pro Glu Gly Lys Tyr Ser Phe Gly 275 280 285 Ala Thr Cys Val Lys Lys Cys Pro Arg Asn Tyr Val Val Thr Asp His 290 295 300 Gly Ser Cys Val Arg Ala Cys Gly Ala Asp Ser Tyr Glu Met Glu Glu 305 310 315 320 Asp Gly Val Arg Lys Cys Lys Lys Cys Glu Gly Pro Cys Arg Lys Val 325 330 335 Cys Asn Gly Ile Gly Ile Gly Glu Phe Lys Asp Ser Leu Ser Ile Asn 340 345 350 Ala Thr Asn Ile Lys His Phe Lys Asn Cys Thr Ser Ile Ser Gly Asp 355 360 365 Leu His Ile Leu Pro Val Ala Phe Arg Gly Asp Ser Phe Thr His Thr 370 375 380 Pro Pro Leu Asp Pro Gln Glu Leu Asp Ile Leu Lys Thr Val Lys Glu 385 390 395 400 Ile Thr Gly Phe Leu Leu Ile Gln Ala Trp Pro Glu Asn Arg Thr Asp 405 410 415 Leu His Ala Phe Glu Asn Leu Glu Ile Ile Arg Gly Arg Thr Lys Gln 420 425 430 His Gly Gln Phe Ser Leu Ala Val Val Ser Leu Asn Ile Thr Ser Leu 435 440 445 Gly Leu Arg Ser Leu Lys Glu Ile Ser Asp Gly Asp Val Ile Ile Ser 450 455 460 Gly Asn Lys Asn Leu Cys Tyr Ala Asn Thr Ile Asn Trp Lys Lys Leu 465 470 475 480 Phe Gly Thr Ser Gly Gln Lys Thr Lys Ile Ile Ser Asn Arg Gly Glu 485 490 495 Asn Ser Cys Lys Ala Thr Gly Gln Val Cys His Ala Leu Cys Ser Pro 500 505 510 Glu Gly Cys Trp Gly Pro Glu Pro Arg Asp Cys Val Ser Cys Arg Asn 515 520 525 Val Ser Arg Gly Arg Glu Cys Val Asp Lys Cys Asn Leu Leu Glu Gly 530 535 540 Glu Pro Arg Glu Phe Val Glu Asn Ser Glu Cys Ile Gln Cys His Pro 545 550 555 560 Glu Cys Leu Pro Gln Ala Met Asn Ile Thr Cys Thr Gly Arg Gly Pro 565 570 575 Asp Asn Cys Ile Gln Cys Ala His Tyr Ile Asp Gly Pro His Cys Val 580 585 590 Lys Thr Cys Pro Ala Gly Val Met Gly Glu Asn Asn Thr Leu Val Trp 595 600 605 Lys Tyr Ala Asp Ala Gly His Val Cys His Leu Cys His Pro Asn Cys 610 615 620 Thr Tyr Gly Pro Gly Asn Glu Ser Leu Lys Ala Met Leu Phe Cys Leu 625 630 635 640 Phe Lys Leu Ser Ser Cys Asn Gln Ser Asn Asp Gly Ser Val Ser His 645 650 655 Gln Ser Gly Ser Pro Ala Ala Gln Glu Ser Cys Leu Gly Trp Ile Pro 660 665 670 Ser Leu Leu Pro Ser Glu Phe Gln Leu Gly Trp Gly Gly Cys Ser His 675 680 685 Leu His Ala Trp Pro Ser Ala Ser Val Ile Ile Thr Ala Ser Ser Cys 690 695 700 His 705 <210> SEQ ID NO 96 <211> LENGTH: 628 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 96 Met Arg Pro Ser Gly Thr Ala Gly Ala Ala Leu Leu Ala Leu Leu Ala 1 5 10 15 Ala Leu Cys Pro Ala Ser Arg Ala Leu Glu Glu Lys Lys Val Cys Gln 20 25 30 Gly Thr Ser Asn Lys Leu Thr Gln Leu Gly Thr Phe Glu Asp His Phe 35 40 45 Leu Ser Leu Gln Arg Met Phe Asn Asn Cys Glu Val Val Leu Gly Asn 50 55 60 Leu Glu Ile Thr Tyr Val Gln Arg Asn Tyr Asp Leu Ser Phe Leu Lys 65 70 75 80 Thr Ile Gln Glu Val Ala Gly Tyr Val Leu Ile Ala Leu Asn Thr Val 85 90 95 Glu Arg Ile Pro Leu Glu Asn Leu Gln Ile Ile Arg Gly Asn Met Tyr 100 105 110 Tyr Glu Asn Ser Tyr Ala Leu Ala Val Leu Ser Asn Tyr Asp Ala Asn 115 120 125 Lys Thr Gly Leu Lys Glu Leu Pro Met Arg Asn Leu Gln Glu Ile Leu 130 135 140 His Gly Ala Val Arg Phe Ser Asn Asn Pro Ala Leu Cys Asn Val Glu 145 150 155 160 Ser Ile Gln Trp Arg Asp Ile Val Ser Ser Asp Phe Leu Ser Asn Met 165 170 175 Ser Met Asp Phe Gln Asn His Leu Gly Ser Cys Gln Lys Cys Asp Pro 180 185 190 Ser Cys Pro Asn Gly Ser Cys Trp Gly Ala Gly Glu Glu Asn Cys Gln 195 200 205 Lys Leu Thr Lys Ile Ile Cys Ala Gln Gln Cys Ser Gly Arg Cys Arg 210 215 220 Gly Lys Ser Pro Ser Asp Cys Cys His Asn Gln Cys Ala Ala Gly Cys 225 230 235 240 Thr Gly Pro Arg Glu Ser Asp Cys Leu Val Cys Arg Lys Phe Arg Asp 245 250 255 Glu Ala Thr Cys Lys Asp Thr Cys Pro Pro Leu Met Leu Tyr Asn Pro 260 265 270 Thr Thr Tyr Gln Met Asp Val Asn Pro Glu Gly Lys Tyr Ser Phe Gly 275 280 285 Ala Thr Cys Val Lys Lys Cys Pro Arg Asn Tyr Val Val Thr Asp His 290 295 300 Gly Ser Cys Val Arg Ala Cys Gly Ala Asp Ser Tyr Glu Met Glu Glu 305 310 315 320 Asp Gly Val Arg Lys Cys Lys Lys Cys Glu Gly Pro Cys Arg Lys Val 325 330 335 Cys Asn Gly Ile Gly Ile Gly Glu Phe Lys Asp Ser Leu Ser Ile Asn 340 345 350 Ala Thr Asn Ile Lys His Phe Lys Asn Cys Thr Ser Ile Ser Gly Asp 355 360 365 Leu His Ile Leu Pro Val Ala Phe Arg Gly Asp Ser Phe Thr His Thr 370 375 380 Pro Pro Leu Asp Pro Gln Glu Leu Asp Ile Leu Lys Thr Val Lys Glu 385 390 395 400 Ile Thr Gly Phe Leu Leu Ile Gln Ala Trp Pro Glu Asn Arg Thr Asp 405 410 415 Leu His Ala Phe Glu Asn Leu Glu Ile Ile Arg Gly Arg Thr Lys Gln 420 425 430 His Gly Gln Phe Ser Leu Ala Val Val Ser Leu Asn Ile Thr Ser Leu 435 440 445 Gly Leu Arg Ser Leu Lys Glu Ile Ser Asp Gly Asp Val Ile Ile Ser 450 455 460 Gly Asn Lys Asn Leu Cys Tyr Ala Asn Thr Ile Asn Trp Lys Lys Leu 465 470 475 480 Phe Gly Thr Ser Gly Gln Lys Thr Lys Ile Ile Ser Asn Arg Gly Glu 485 490 495 Asn Ser Cys Lys Ala Thr Gly Gln Val Cys His Ala Leu Cys Ser Pro 500 505 510 Glu Gly Cys Trp Gly Pro Glu Pro Arg Asp Cys Val Ser Cys Arg Asn 515 520 525 Val Ser Arg Gly Arg Glu Cys Val Asp Lys Cys Asn Leu Leu Glu Gly 530 535 540 Glu Pro Arg Glu Phe Val Glu Asn Ser Glu Cys Ile Gln Cys His Pro 545 550 555 560 Glu Cys Leu Pro Gln Ala Met Asn Ile Thr Cys Thr Gly Arg Gly Pro 565 570 575 Asp Asn Cys Ile Gln Cys Ala His Tyr Ile Asp Gly Pro His Cys Val 580 585 590 Lys Thr Cys Pro Ala Gly Val Met Gly Glu Asn Asn Thr Leu Val Trp 595 600 605 Lys Tyr Ala Asp Ala Gly His Val Cys His Leu Cys His Pro Asn Cys 610 615 620 Thr Tyr Gly Ser 625 <210> SEQ ID NO 97 <211> LENGTH: 242 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 97 Met Ser Gly Cys Asp Ala Arg Glu Gly Asp Cys Cys Ser Arg Arg Cys 1 5 10 15 Gly Ala Gln Asp Lys Glu His Pro Arg Tyr Leu Ile Pro Glu Leu Cys 20 25 30 Lys Gln Phe Tyr His Leu Gly Trp Val Thr Gly Thr Gly Gly Gly Ile 35 40 45 Ser Leu Lys His Gly Asp Glu Ile Tyr Ile Ala Pro Ser Gly Val Gln 50 55 60 Lys Glu Arg Ile Gln Pro Glu Asp Met Phe Val Cys Asp Ile Asn Glu 65 70 75 80 Lys Asp Ile Ser Gly Pro Ser Pro Ser Lys Lys Leu Lys Lys Ser Gln 85 90 95 Cys Thr Pro Leu Phe Met Asn Ala Tyr Thr Met Arg Gly Ala Gly Ala 100 105 110 Val Ile His Thr His Ser Lys Ala Ala Val Met Ala Thr Leu Leu Phe 115 120 125 Pro Gly Arg Glu Phe Lys Ile Thr His Gln Glu Met Ile Lys Gly Ile 130 135 140 Lys Lys Cys Thr Ser Gly Gly Tyr Tyr Arg Tyr Asp Asp Met Leu Val 145 150 155 160 Val Pro Ile Ile Glu Asn Thr Pro Glu Glu Lys Asp Leu Lys Asp Arg 165 170 175 Met Ala His Ala Met Asn Glu Tyr Pro Asp Ser Cys Ala Val Leu Val 180 185 190 Arg Arg His Gly Val Tyr Val Trp Gly Glu Thr Trp Glu Lys Ala Lys 195 200 205 Thr Met Cys Glu Cys Tyr Asp Tyr Leu Phe Asp Ile Ala Val Ser Met 210 215 220 Lys Lys Val Gly Leu Asp Pro Ser Gln Leu Pro Val Gly Glu Asn Gly 225 230 235 240 Ile Val <210> SEQ ID NO 98 <211> LENGTH: 367 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 98 Met Arg Trp Phe Leu Pro Trp Thr Leu Ala Ala Val Thr Ala Ala Ala 1 5 10 15 Ala Ser Thr Val Leu Ala Thr Ala Leu Ser Pro Ala Pro Thr Thr Met 20 25 30 Asp Phe Thr Pro Ala Pro Leu Glu Asp Thr Ser Ser Arg Pro Gln Phe 35 40 45 Cys Lys Trp Pro Cys Glu Cys Pro Pro Ser Pro Pro Arg Cys Pro Leu 50 55 60 Gly Val Ser Leu Ile Thr Asp Gly Cys Glu Cys Cys Lys Met Cys Ala 65 70 75 80 Gln Gln Leu Gly Asp Asn Cys Thr Glu Ala Ala Ile Cys Asp Pro His 85 90 95 Arg Gly Leu Tyr Cys Asp Tyr Ser Gly Asp Arg Pro Arg Tyr Ala Ile 100 105 110 Gly Val Cys Ala Gln Val Val Gly Val Gly Cys Val Leu Asp Gly Val 115 120 125 Arg Tyr Asn Asn Gly Gln Ser Phe Gln Pro Asn Cys Lys Tyr Asn Cys 130 135 140 Thr Cys Ile Asp Gly Ala Val Gly Cys Thr Pro Leu Cys Leu Arg Val 145 150 155 160 Arg Pro Pro Arg Leu Trp Cys Pro His Pro Arg Arg Val Ser Ile Pro 165 170 175 Gly His Cys Cys Glu Gln Trp Val Cys Glu Asp Asp Ala Lys Arg Pro 180 185 190 Arg Lys Thr Ala Pro Arg Asp Thr Gly Ala Phe Asp Ala Val Gly Glu 195 200 205 Val Glu Ala Trp His Arg Asn Cys Ile Ala Tyr Thr Ser Pro Trp Ser 210 215 220 Pro Cys Ser Thr Ser Cys Gly Leu Gly Val Ser Thr Arg Ile Ser Asn 225 230 235 240 Val Asn Ala Gln Cys Trp Pro Glu Gln Glu Ser Arg Leu Cys Asn Leu 245 250 255 Arg Pro Cys Asp Val Asp Ile His Thr Leu Ile Lys Ala Gly Lys Lys 260 265 270 Cys Leu Ala Val Tyr Gln Pro Glu Ala Ser Met Asn Phe Thr Leu Ala 275 280 285 Gly Cys Ile Ser Thr Arg Ser Tyr Gln Pro Lys Tyr Cys Gly Val Cys 290 295 300 Met Asp Asn Arg Cys Cys Ile Pro Tyr Lys Ser Lys Thr Ile Asp Val 305 310 315 320 Ser Phe Gln Cys Pro Asp Gly Leu Gly Phe Ser Arg Gln Val Leu Trp 325 330 335 Ile Asn Ala Cys Phe Cys Asn Leu Ser Cys Arg Asn Pro Asn Asp Ile 340 345 350 Phe Ala Asp Leu Glu Ser Tyr Pro Asp Phe Ser Glu Ile Ala Asn 355 360 365 <210> SEQ ID NO 99 <211> LENGTH: 280 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 99 Met Arg Trp Phe Leu Pro Trp Thr Leu Ala Ala Val Thr Ala Ala Ala 1 5 10 15 Ala Ser Thr Val Leu Ala Thr Ala Leu Ser Pro Ala Pro Thr Thr Met 20 25 30 Asp Phe Thr Pro Ala Pro Leu Glu Asp Thr Ser Ser Arg Pro Gln Phe 35 40 45 Cys Lys Trp Pro Cys Glu Cys Pro Pro Ser Pro Pro Arg Cys Pro Leu 50 55 60 Gly Val Ser Leu Ile Thr Asp Gly Cys Glu Cys Cys Lys Met Cys Ala 65 70 75 80 Gln Gln Leu Gly Asp Asn Cys Thr Glu Ala Ala Ile Cys Asp Pro His 85 90 95 Arg Gly Leu Tyr Cys Asp Tyr Ser Gly Asp Arg Pro Arg Tyr Ala Ile 100 105 110 Gly Val Cys Ala His Ala Val Gly Glu Val Glu Ala Trp His Arg Asn 115 120 125 Cys Ile Ala Tyr Thr Ser Pro Trp Ser Pro Cys Ser Thr Ser Cys Gly 130 135 140 Leu Gly Val Ser Thr Arg Ile Ser Asn Val Asn Ala Gln Cys Trp Pro 145 150 155 160 Glu Gln Glu Ser Arg Leu Cys Asn Leu Arg Pro Cys Asp Val Asp Ile 165 170 175 His Thr Leu Ile Lys Ala Gly Lys Lys Cys Leu Ala Val Tyr Gln Pro 180 185 190 Glu Ala Ser Met Asn Phe Thr Leu Ala Gly Cys Ile Ser Thr Arg Ser 195 200 205 Tyr Gln Pro Lys Tyr Cys Gly Val Cys Met Asp Asn Arg Cys Cys Ile 210 215 220 Pro Tyr Lys Ser Lys Thr Ile Asp Val Ser Phe Gln Cys Pro Asp Gly 225 230 235 240 Leu Gly Phe Ser Arg Gln Val Leu Trp Ile Asn Ala Cys Phe Cys Asn 245 250 255 Leu Ser Cys Arg Asn Pro Asn Asp Ile Phe Ala Asp Leu Glu Ser Tyr 260 265 270 Pro Asp Phe Ser Glu Ile Ala Asn 275 280 <210> SEQ ID NO 100 <211> LENGTH: 370 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 100 Met Gly Leu Trp Ala Leu Leu Pro Gly Trp Val Ser Ala Thr Leu Leu 1 5 10 15 Leu Ala Leu Ala Ala Leu Pro Ala Ala Leu Ala Ala Asn Ser Ser Gly 20 25 30 Arg Trp Trp Gly Ile Val Asn Val Ala Ser Ser Thr Asn Leu Leu Thr 35 40 45 Asp Ser Lys Ser Leu Gln Leu Val Leu Glu Pro Ser Leu Gln Leu Leu 50 55 60 Ser Arg Lys Gln Arg Arg Leu Ile Arg Gln Asn Pro Gly Ile Leu His 65 70 75 80 Ser Val Ser Gly Gly Leu Gln Ser Ala Val Arg Glu Cys Lys Trp Gln 85 90 95 Phe Arg Asn Arg Arg Trp Asn Cys Pro Thr Ala Pro Gly Pro His Leu 100 105 110 Phe Gly Lys Ile Val Asn Arg Gly Cys Arg Glu Thr Ala Phe Ile Phe 115 120 125 Ala Ile Thr Ser Ala Gly Val Thr His Ser Val Ala Arg Ser Cys Ser 130 135 140 Glu Gly Ser Ile Glu Ser Cys Thr Cys Asp Tyr Arg Arg Arg Gly Pro 145 150 155 160 Gly Gly Pro Asp Trp His Trp Gly Gly Cys Ser Asp Asn Ile Asp Phe 165 170 175 Gly Arg Leu Phe Gly Arg Glu Phe Val Asp Ser Gly Glu Lys Gly Arg 180 185 190 Asp Leu Arg Phe Leu Met Asn Leu His Asn Asn Glu Ala Gly Arg Thr 195 200 205 Thr Val Phe Ser Glu Met Arg Gln Glu Cys Lys Cys His Gly Met Ser 210 215 220 Gly Ser Cys Thr Val Arg Thr Cys Trp Met Arg Leu Pro Thr Leu Arg 225 230 235 240 Ala Val Gly Asp Val Leu Arg Asp Arg Phe Asp Gly Ala Ser Arg Val 245 250 255 Leu Tyr Gly Asn Arg Gly Ser Asn Arg Ala Ser Arg Ala Glu Leu Leu 260 265 270 Arg Leu Glu Pro Glu Asp Pro Ala His Lys Pro Pro Ser Pro His Asp 275 280 285 Leu Val Tyr Phe Glu Lys Ser Pro Asn Phe Cys Thr Tyr Ser Gly Arg 290 295 300 Leu Gly Thr Ala Gly Thr Ala Gly Arg Ala Cys Asn Ser Ser Ser Pro 305 310 315 320 Ala Leu Asp Gly Cys Glu Leu Leu Cys Cys Gly Arg Gly His Arg Thr 325 330 335 Arg Thr Gln Arg Val Thr Glu Arg Cys Asn Cys Thr Phe His Trp Cys 340 345 350 Cys His Val Ser Cys Arg Asn Cys Thr His Thr Arg Val Leu His Glu 355 360 365 Cys Leu 370 <210> SEQ ID NO 101 <211> LENGTH: 648 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 101 Met Glu His Ile Gln Gly Ala Trp Lys Thr Ile Ser Asn Gly Phe Gly 1 5 10 15 Phe Lys Asp Ala Val Phe Asp Gly Ser Ser Cys Ile Ser Pro Thr Ile 20 25 30 Val Gln Gln Phe Gly Tyr Gln Arg Arg Ala Ser Asp Asp Gly Lys Leu 35 40 45 Thr Asp Pro Ser Lys Thr Ser Asn Thr Ile Arg Val Phe Leu Pro Asn 50 55 60 Lys Gln Arg Thr Val Val Asn Val Arg Asn Gly Met Ser Leu His Asp 65 70 75 80 Cys Leu Met Lys Ala Leu Lys Val Arg Gly Leu Gln Pro Glu Cys Cys 85 90 95 Ala Val Phe Arg Leu Leu His Glu His Lys Gly Lys Lys Ala Arg Leu 100 105 110 Asp Trp Asn Thr Asp Ala Ala Ser Leu Ile Gly Glu Glu Leu Gln Val 115 120 125 Asp Phe Leu Asp His Val Pro Leu Thr Thr His Asn Phe Ala Arg Lys 130 135 140 Thr Phe Leu Lys Leu Ala Phe Cys Asp Ile Cys Gln Lys Phe Leu Leu 145 150 155 160 Asn Gly Phe Arg Cys Gln Thr Cys Gly Tyr Lys Phe His Glu His Cys 165 170 175 Ser Thr Lys Val Pro Thr Met Cys Val Asp Trp Ser Asn Ile Arg Gln 180 185 190 Leu Leu Leu Phe Pro Asn Ser Thr Ile Gly Asp Ser Gly Val Pro Ala 195 200 205 Leu Pro Ser Leu Thr Met Arg Arg Met Arg Glu Ser Val Ser Arg Met 210 215 220 Pro Val Ser Ser Gln His Arg Tyr Ser Thr Pro His Ala Phe Thr Phe 225 230 235 240 Asn Thr Ser Ser Pro Ser Ser Glu Gly Ser Leu Ser Gln Arg Gln Arg 245 250 255 Ser Thr Ser Thr Pro Asn Val His Met Val Ser Thr Thr Leu Pro Val 260 265 270 Asp Ser Arg Met Ile Glu Asp Ala Ile Arg Ser His Ser Glu Ser Ala 275 280 285 Ser Pro Ser Ala Leu Ser Ser Ser Pro Asn Asn Leu Ser Pro Thr Gly 290 295 300 Trp Ser Gln Pro Lys Thr Pro Val Pro Ala Gln Arg Glu Arg Ala Pro 305 310 315 320 Val Ser Gly Thr Gln Glu Lys Asn Lys Ile Arg Pro Arg Gly Gln Arg 325 330 335 Asp Ser Ser Tyr Tyr Trp Glu Ile Glu Ala Ser Glu Val Met Leu Ser 340 345 350 Thr Arg Ile Gly Ser Gly Ser Phe Gly Thr Val Tyr Lys Gly Lys Trp 355 360 365 His Gly Asp Val Ala Val Lys Ile Leu Lys Val Val Asp Pro Thr Pro 370 375 380 Glu Gln Phe Gln Ala Phe Arg Asn Glu Val Ala Val Leu Arg Lys Thr 385 390 395 400 Arg His Val Asn Ile Leu Leu Phe Met Gly Tyr Met Thr Lys Asp Asn 405 410 415 Leu Ala Ile Val Thr Gln Trp Cys Glu Gly Ser Ser Leu Tyr Lys His 420 425 430 Leu His Val Gln Glu Thr Lys Phe Gln Met Phe Gln Leu Ile Asp Ile 435 440 445 Ala Arg Gln Thr Ala Gln Gly Met Asp Tyr Leu His Ala Lys Asn Ile 450 455 460 Ile His Arg Asp Met Lys Ser Asn Asn Ile Phe Leu His Glu Gly Leu 465 470 475 480 Thr Val Lys Ile Gly Asp Phe Gly Leu Ala Thr Val Lys Ser Arg Trp 485 490 495 Ser Gly Ser Gln Gln Val Glu Gln Pro Thr Gly Ser Val Leu Trp Met 500 505 510 Ala Pro Glu Val Ile Arg Met Gln Asp Asn Asn Pro Phe Ser Phe Gln 515 520 525 Ser Asp Val Tyr Ser Tyr Gly Ile Val Leu Tyr Glu Leu Met Thr Gly 530 535 540 Glu Leu Pro Tyr Ser His Ile Asn Asn Arg Asp Gln Ile Ile Phe Met 545 550 555 560 Val Gly Arg Gly Tyr Ala Ser Pro Asp Leu Ser Lys Leu Tyr Lys Asn 565 570 575 Cys Pro Lys Ala Met Lys Arg Leu Val Ala Asp Cys Val Lys Lys Val 580 585 590 Lys Glu Glu Arg Pro Leu Phe Pro Gln Ile Leu Ser Ser Ile Glu Leu 595 600 605 Leu Gln His Ser Leu Pro Lys Ile Asn Arg Ser Ala Ser Glu Pro Ser 610 615 620 Leu His Arg Ala Ala His Thr Glu Asp Ile Asn Ala Cys Thr Leu Thr 625 630 635 640 Thr Ser Pro Arg Leu Pro Val Phe 645 <210> SEQ ID NO 102 <211> LENGTH: 536 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 102 Met Gly Ser Asn Lys Ser Lys Pro Lys Asp Ala Ser Gln Arg Arg Arg 1 5 10 15 Ser Leu Glu Pro Ala Glu Asn Val His Gly Ala Gly Gly Gly Ala Phe 20 25 30 Pro Ala Ser Gln Thr Pro Ser Lys Pro Ala Ser Ala Asp Gly His Arg 35 40 45 Gly Pro Ser Ala Ala Phe Ala Pro Ala Ala Ala Glu Pro Lys Leu Phe 50 55 60 Gly Gly Phe Asn Ser Ser Asp Thr Val Thr Ser Pro Gln Arg Ala Gly 65 70 75 80 Pro Leu Ala Gly Gly Val Thr Thr Phe Val Ala Leu Tyr Asp Tyr Glu 85 90 95 Ser Arg Thr Glu Thr Asp Leu Ser Phe Lys Lys Gly Glu Arg Leu Gln 100 105 110 Ile Val Asn Asn Thr Glu Gly Asp Trp Trp Leu Ala His Ser Leu Ser 115 120 125 Thr Gly Gln Thr Gly Tyr Ile Pro Ser Asn Tyr Val Ala Pro Ser Asp 130 135 140 Ser Ile Gln Ala Glu Glu Trp Tyr Phe Gly Lys Ile Thr Arg Arg Glu 145 150 155 160 Ser Glu Arg Leu Leu Leu Asn Ala Glu Asn Pro Arg Gly Thr Phe Leu 165 170 175 Val Arg Glu Ser Glu Thr Thr Lys Gly Ala Tyr Cys Leu Ser Val Ser 180 185 190 Asp Phe Asp Asn Ala Lys Gly Leu Asn Val Lys His Tyr Lys Ile Arg 195 200 205 Lys Leu Asp Ser Gly Gly Phe Tyr Ile Thr Ser Arg Thr Gln Phe Asn 210 215 220 Ser Leu Gln Gln Leu Val Ala Tyr Tyr Ser Lys His Ala Asp Gly Leu 225 230 235 240 Cys His Arg Leu Thr Thr Val Cys Pro Thr Ser Lys Pro Gln Thr Gln 245 250 255 Gly Leu Ala Lys Asp Ala Trp Glu Ile Pro Arg Glu Ser Leu Arg Leu 260 265 270 Glu Val Lys Leu Gly Gln Gly Cys Phe Gly Glu Val Trp Met Gly Thr 275 280 285 Trp Asn Gly Thr Thr Arg Val Ala Ile Lys Thr Leu Lys Pro Gly Thr 290 295 300 Met Ser Pro Glu Ala Phe Leu Gln Glu Ala Gln Val Met Lys Lys Leu 305 310 315 320 Arg His Glu Lys Leu Val Gln Leu Tyr Ala Val Val Ser Glu Glu Pro 325 330 335 Ile Tyr Ile Val Thr Glu Tyr Met Ser Lys Gly Ser Leu Leu Asp Phe 340 345 350 Leu Lys Gly Glu Thr Gly Lys Tyr Leu Arg Leu Pro Gln Leu Val Asp 355 360 365 Met Ala Ala Gln Ile Ala Ser Gly Met Ala Tyr Val Glu Arg Met Asn 370 375 380 Tyr Val His Arg Asp Leu Arg Ala Ala Asn Ile Leu Val Gly Glu Asn 385 390 395 400 Leu Val Cys Lys Val Ala Asp Phe Gly Leu Ala Arg Leu Ile Glu Asp 405 410 415 Asn Glu Tyr Thr Ala Arg Gln Gly Ala Lys Phe Pro Ile Lys Trp Thr 420 425 430 Ala Pro Glu Ala Ala Leu Tyr Gly Arg Phe Thr Ile Lys Ser Asp Val 435 440 445 Trp Ser Phe Gly Ile Leu Leu Thr Glu Leu Thr Thr Lys Gly Arg Val 450 455 460 Pro Tyr Pro Gly Met Val Asn Arg Glu Val Leu Asp Gln Val Glu Arg 465 470 475 480 Gly Tyr Arg Met Pro Cys Pro Pro Glu Cys Pro Glu Ser Leu His Asp 485 490 495 Leu Met Cys Gln Cys Trp Arg Lys Glu Pro Glu Glu Arg Pro Thr Phe 500 505 510 Glu Tyr Leu Gln Ala Phe Leu Glu Asp Tyr Phe Thr Ser Thr Glu Pro 515 520 525 Gln Tyr Gln Pro Gly Glu Asn Leu 530 535 <210> SEQ ID NO 103 <211> LENGTH: 480 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 103 Met Ser Asp Val Ala Ile Val Lys Glu Gly Trp Leu His Lys Arg Gly 1 5 10 15 Glu Tyr Ile Lys Thr Trp Arg Pro Arg Tyr Phe Leu Leu Lys Asn Asp 20 25 30 Gly Thr Phe Ile Gly Tyr Lys Glu Arg Pro Gln Asp Val Asp Gln Arg 35 40 45 Glu Ala Pro Leu Asn Asn Phe Ser Val Ala Gln Cys Gln Leu Met Lys 50 55 60 Thr Glu Arg Pro Arg Pro Asn Thr Phe Ile Ile Arg Cys Leu Gln Trp 65 70 75 80 Thr Thr Val Ile Glu Arg Thr Phe His Val Glu Thr Pro Glu Glu Arg 85 90 95 Glu Glu Trp Thr Thr Ala Ile Gln Thr Val Ala Asp Gly Leu Lys Lys 100 105 110 Gln Glu Glu Glu Glu Met Asp Phe Arg Ser Gly Ser Pro Ser Asp Asn 115 120 125 Ser Gly Ala Glu Glu Met Glu Val Ser Leu Ala Lys Pro Lys His Arg 130 135 140 Val Thr Met Asn Glu Phe Glu Tyr Leu Lys Leu Leu Gly Lys Gly Thr 145 150 155 160 Phe Gly Lys Val Ile Leu Val Lys Glu Lys Ala Thr Gly Arg Tyr Tyr 165 170 175 Ala Met Lys Ile Leu Lys Lys Glu Val Ile Val Ala Lys Asp Glu Val 180 185 190 Ala His Thr Leu Thr Glu Asn Arg Val Leu Gln Asn Ser Arg His Pro 195 200 205 Phe Leu Thr Ala Leu Lys Tyr Ser Phe Gln Thr His Asp Arg Leu Cys 210 215 220 Phe Val Met Glu Tyr Ala Asn Gly Gly Glu Leu Phe Phe His Leu Ser 225 230 235 240 Arg Glu Arg Val Phe Ser Glu Asp Arg Ala Arg Phe Tyr Gly Ala Glu 245 250 255 Ile Val Ser Ala Leu Asp Tyr Leu His Ser Glu Lys Asn Val Val Tyr 260 265 270 Arg Asp Leu Lys Leu Glu Asn Leu Met Leu Asp Lys Asp Gly His Ile 275 280 285 Lys Ile Thr Asp Phe Gly Leu Cys Lys Glu Gly Ile Lys Asp Gly Ala 290 295 300 Thr Met Lys Thr Phe Cys Gly Thr Pro Glu Tyr Leu Ala Pro Glu Val 305 310 315 320 Leu Glu Asp Asn Asp Tyr Gly Arg Ala Val Asp Trp Trp Gly Leu Gly 325 330 335 Val Val Met Tyr Glu Met Met Cys Gly Arg Leu Pro Phe Tyr Asn Gln 340 345 350 Asp His Glu Lys Leu Phe Glu Leu Ile Leu Met Glu Glu Ile Arg Phe 355 360 365 Pro Arg Thr Leu Gly Pro Glu Ala Lys Ser Leu Leu Ser Gly Leu Leu 370 375 380 Lys Lys Asp Pro Lys Gln Arg Leu Gly Gly Gly Ser Glu Asp Ala Lys 385 390 395 400 Glu Ile Met Gln His Arg Phe Phe Ala Gly Ile Val Trp Gln His Val 405 410 415 Tyr Glu Lys Lys Leu Ser Pro Pro Phe Lys Pro Gln Val Thr Ser Glu 420 425 430 Thr Asp Thr Arg Tyr Phe Asp Glu Glu Phe Thr Ala Gln Met Ile Thr 435 440 445 Ile Thr Pro Pro Asp Gln Asp Asp Ser Met Glu Cys Val Asp Ser Glu 450 455 460 Arg Arg Pro His Phe Pro Gln Phe Ser Tyr Ser Ala Ser Gly Thr Ala 465 470 475 480 <210> SEQ ID NO 104 <211> LENGTH: 379 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 104 Met Ala Ala Ala Ala Ala Gln Gly Gly Gly Gly Gly Glu Pro Arg Arg 1 5 10 15 Thr Glu Gly Val Gly Pro Gly Val Pro Gly Glu Val Glu Met Val Lys 20 25 30 Gly Gln Pro Phe Asp Val Gly Pro Arg Tyr Thr Gln Leu Gln Tyr Ile 35 40 45 Gly Glu Gly Ala Tyr Gly Met Val Ser Ser Ala Tyr Asp His Val Arg 50 55 60 Lys Thr Arg Val Ala Ile Lys Lys Ile Ser Pro Phe Glu His Gln Thr 65 70 75 80 Tyr Cys Gln Arg Thr Leu Arg Glu Ile Gln Ile Leu Leu Arg Phe Arg 85 90 95 His Glu Asn Val Ile Gly Ile Arg Asp Ile Leu Arg Ala Ser Thr Leu 100 105 110 Glu Ala Met Arg Asp Val Tyr Ile Val Gln Asp Leu Met Glu Thr Asp 115 120 125 Leu Tyr Lys Leu Leu Lys Ser Gln Gln Leu Ser Asn Asp His Ile Cys 130 135 140 Tyr Phe Leu Tyr Gln Ile Leu Arg Gly Leu Lys Tyr Ile His Ser Ala 145 150 155 160 Asn Val Leu His Arg Asp Leu Lys Pro Ser Asn Leu Leu Ile Asn Thr 165 170 175 Thr Cys Asp Leu Lys Ile Cys Asp Phe Gly Leu Ala Arg Ile Ala Asp 180 185 190 Pro Glu His Asp His Thr Gly Phe Leu Thr Glu Tyr Val Ala Thr Arg 195 200 205 Trp Tyr Arg Ala Pro Glu Ile Met Leu Asn Ser Lys Gly Tyr Thr Lys 210 215 220 Ser Ile Asp Ile Trp Ser Val Gly Cys Ile Leu Ala Glu Met Leu Ser 225 230 235 240 Asn Arg Pro Ile Phe Pro Gly Lys His Tyr Leu Asp Gln Leu Asn His 245 250 255 Ile Leu Gly Ile Leu Gly Ser Pro Ser Gln Glu Asp Leu Asn Cys Ile 260 265 270 Ile Asn Met Lys Ala Arg Asn Tyr Leu Gln Ser Leu Pro Ser Lys Thr 275 280 285 Lys Val Ala Trp Ala Lys Leu Phe Pro Lys Ser Asp Ser Lys Ala Leu 290 295 300 Asp Leu Leu Asp Arg Met Leu Thr Phe Asn Pro Asn Lys Arg Ile Thr 305 310 315 320 Val Glu Glu Ala Leu Ala His Pro Tyr Leu Glu Gln Tyr Tyr Asp Pro 325 330 335 Thr Asp Glu Pro Val Ala Glu Glu Pro Phe Thr Phe Ala Met Glu Leu 340 345 350 Asp Asp Leu Pro Lys Glu Arg Leu Lys Glu Leu Ile Phe Gln Glu Thr 355 360 365 Ala Arg Phe Gln Pro Gly Val Leu Glu Ala Pro 370 375 <210> SEQ ID NO 105 <211> LENGTH: 360 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 105 Met Ala Ala Ala Ala Ala Ala Gly Ala Gly Pro Glu Met Val Arg Gly 1 5 10 15 Gln Val Phe Asp Val Gly Pro Arg Tyr Thr Asn Leu Ser Tyr Ile Gly 20 25 30 Glu Gly Ala Tyr Gly Met Val Cys Ser Ala Tyr Asp Asn Val Asn Lys 35 40 45 Val Arg Val Ala Ile Lys Lys Ile Ser Pro Phe Glu His Gln Thr Tyr 50 55 60 Cys Gln Arg Thr Leu Arg Glu Ile Lys Ile Leu Leu Arg Phe Arg His 65 70 75 80 Glu Asn Ile Ile Gly Ile Asn Asp Ile Ile Arg Ala Pro Thr Ile Glu 85 90 95 Gln Met Lys Asp Val Tyr Ile Val Gln Asp Leu Met Glu Thr Asp Leu 100 105 110 Tyr Lys Leu Leu Lys Thr Gln His Leu Ser Asn Asp His Ile Cys Tyr 115 120 125 Phe Leu Tyr Gln Ile Leu Arg Gly Leu Lys Tyr Ile His Ser Ala Asn 130 135 140 Val Leu His Arg Asp Leu Lys Pro Ser Asn Leu Leu Leu Asn Thr Thr 145 150 155 160 Cys Asp Leu Lys Ile Cys Asp Phe Gly Leu Ala Arg Val Ala Asp Pro 165 170 175 Asp His Asp His Thr Gly Phe Leu Thr Glu Tyr Val Ala Thr Arg Trp 180 185 190 Tyr Arg Ala Pro Glu Ile Met Leu Asn Ser Lys Gly Tyr Thr Lys Ser 195 200 205 Ile Asp Ile Trp Ser Val Gly Cys Ile Leu Ala Glu Met Leu Ser Asn 210 215 220 Arg Pro Ile Phe Pro Gly Lys His Tyr Leu Asp Gln Leu Asn His Ile 225 230 235 240 Leu Gly Ile Leu Gly Ser Pro Ser Gln Glu Asp Leu Asn Cys Ile Ile 245 250 255 Asn Leu Lys Ala Arg Asn Tyr Leu Leu Ser Leu Pro His Lys Asn Lys 260 265 270 Val Pro Trp Asn Arg Leu Phe Pro Asn Ala Asp Ser Lys Ala Leu Asp 275 280 285 Leu Leu Asp Lys Met Leu Thr Phe Asn Pro His Lys Arg Ile Glu Val 290 295 300 Glu Gln Ala Leu Ala His Pro Tyr Leu Glu Gln Tyr Tyr Asp Pro Ser 305 310 315 320 Asp Glu Pro Ile Ala Glu Ala Pro Phe Lys Phe Asp Met Glu Leu Asp 325 330 335 Asp Leu Pro Lys Glu Lys Leu Lys Glu Leu Ile Phe Glu Glu Thr Ala 340 345 350 Arg Phe Gln Pro Gly Tyr Arg Ser 355 360 <210> SEQ ID NO 106 <211> LENGTH: 239 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 106 Met Ala His Ala Gly Arg Thr Gly Tyr Asp Asn Arg Glu Ile Val Met 1 5 10 15 Lys Tyr Ile His Tyr Lys Leu Ser Gln Arg Gly Tyr Glu Trp Asp Ala 20 25 30 Gly Asp Val Gly Ala Ala Pro Pro Gly Ala Ala Pro Ala Pro Gly Ile 35 40 45 Phe Ser Ser Gln Pro Gly His Thr Pro His Pro Ala Ala Ser Arg Asp 50 55 60 Pro Val Ala Arg Thr Ser Pro Leu Gln Thr Pro Ala Ala Pro Gly Ala 65 70 75 80 Ala Ala Gly Pro Ala Leu Ser Pro Val Pro Pro Val Val His Leu Thr 85 90 95 Leu Arg Gln Ala Gly Asp Asp Phe Ser Arg Arg Tyr Arg Arg Asp Phe 100 105 110 Ala Glu Met Ser Ser Gln Leu His Leu Thr Pro Phe Thr Ala Arg Gly 115 120 125 Arg Phe Ala Thr Val Val Glu Glu Leu Phe Arg Asp Gly Val Asn Trp 130 135 140 Gly Arg Ile Val Ala Phe Phe Glu Phe Gly Gly Val Met Cys Val Glu 145 150 155 160 Ser Val Asn Arg Glu Met Ser Pro Leu Val Asp Asn Ile Ala Leu Trp 165 170 175 Met Thr Glu Tyr Leu Asn Arg His Leu His Thr Trp Ile Gln Asp Asn 180 185 190 Gly Gly Trp Asp Ala Phe Val Glu Leu Tyr Gly Pro Ser Met Arg Pro 195 200 205 Leu Phe Asp Phe Ser Trp Leu Ser Leu Lys Thr Leu Leu Ser Leu Ala 210 215 220 Leu Val Gly Ala Cys Ile Thr Leu Gly Ala Tyr Leu Gly His Lys 225 230 235 <210> SEQ ID NO 107 <211> LENGTH: 99 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 107 Met Thr Ser Lys Leu Ala Val Ala Leu Leu Ala Ala Phe Leu Ile Ser 1 5 10 15 Ala Ala Leu Cys Glu Gly Ala Val Leu Pro Arg Ser Ala Lys Glu Leu 20 25 30 Arg Cys Gln Cys Ile Lys Thr Tyr Ser Lys Pro Phe His Pro Lys Phe 35 40 45 Ile Lys Glu Leu Arg Val Ile Glu Ser Gly Pro His Cys Ala Asn Thr 50 55 60 Glu Ile Ile Val Lys Leu Ser Asp Gly Arg Glu Leu Cys Leu Asp Pro 65 70 75 80 Lys Glu Asn Trp Val Gln Arg Val Val Glu Lys Phe Leu Lys Arg Ala 85 90 95 Glu Asn Ser <210> SEQ ID NO 108 <211> LENGTH: 107 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 108 Met Ala Arg Ala Ala Leu Ser Ala Ala Pro Ser Asn Pro Arg Leu Leu 1 5 10 15 Arg Val Ala Leu Leu Leu Leu Leu Leu Val Ala Ala Gly Arg Arg Ala 20 25 30 Ala Gly Ala Ser Val Ala Thr Glu Leu Arg Cys Gln Cys Leu Gln Thr 35 40 45 Leu Gln Gly Ile His Pro Lys Asn Ile Gln Ser Val Asn Val Lys Ser 50 55 60 Pro Gly Pro His Cys Ala Gln Thr Glu Val Ile Ala Thr Leu Lys Asn 65 70 75 80 Gly Arg Lys Ala Cys Leu Asn Pro Ala Ser Pro Ile Val Lys Lys Ile 85 90 95 Ile Glu Lys Met Leu Asn Ser Asp Lys Ser Asn 100 105 <210> SEQ ID NO 109 <211> LENGTH: 350 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 109 Met Ser Asn Ile Thr Asp Pro Gln Met Trp Asp Phe Asp Asp Leu Asn 1 5 10 15 Phe Thr Gly Met Pro Pro Ala Asp Glu Asp Tyr Ser Pro Cys Met Leu 20 25 30 Glu Thr Glu Thr Leu Asn Lys Tyr Val Val Ile Ile Ala Tyr Ala Leu 35 40 45 Val Phe Leu Leu Ser Leu Leu Gly Asn Ser Leu Val Met Leu Val Ile 50 55 60 Leu Tyr Ser Arg Val Gly Arg Ser Val Thr Asp Val Tyr Leu Leu Asn 65 70 75 80 Leu Ala Leu Ala Asp Leu Leu Phe Ala Leu Thr Leu Pro Ile Trp Ala 85 90 95 Ala Ser Lys Val Asn Gly Trp Ile Phe Gly Thr Phe Leu Cys Lys Val 100 105 110 Val Ser Leu Leu Lys Glu Val Asn Phe Tyr Ser Gly Ile Leu Leu Leu 115 120 125 Ala Cys Ile Ser Val Asp Arg Tyr Leu Ala Ile Val His Ala Thr Arg 130 135 140 Thr Leu Thr Gln Lys Arg His Leu Val Lys Phe Val Cys Leu Gly Cys 145 150 155 160 Trp Gly Leu Ser Met Asn Leu Ser Leu Pro Phe Phe Leu Phe Arg Gln 165 170 175 Ala Tyr His Pro Asn Asn Ser Ser Pro Val Cys Tyr Glu Val Leu Gly 180 185 190 Asn Asp Thr Ala Lys Trp Arg Met Val Leu Arg Ile Leu Pro His Thr 195 200 205 Phe Gly Phe Ile Val Pro Leu Phe Val Met Leu Phe Cys Tyr Gly Phe 210 215 220 Thr Leu Arg Thr Leu Phe Lys Ala His Met Gly Gln Lys His Arg Ala 225 230 235 240 Met Arg Val Ile Phe Ala Val Val Leu Ile Phe Leu Leu Cys Trp Leu 245 250 255 Pro Tyr Asn Leu Val Leu Leu Ala Asp Thr Leu Met Arg Thr Gln Val 260 265 270 Ile Gln Glu Ser Cys Glu Arg Arg Asn Asn Ile Gly Arg Ala Leu Asp 275 280 285 Ala Thr Glu Ile Leu Gly Phe Leu His Ser Cys Leu Asn Pro Ile Ile 290 295 300 Tyr Ala Phe Ile Gly Gln Asn Phe Arg His Gly Phe Leu Lys Ile Leu 305 310 315 320 Ala Met His Gly Leu Val Ser Lys Glu Phe Leu Ala Arg His Arg Val 325 330 335 Thr Ser Tyr Thr Ser Ser Ser Val Asn Val Ser Ser Asn Leu 340 345 350 <210> SEQ ID NO 110 <211> LENGTH: 360 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 110 Met Glu Asp Phe Asn Met Glu Ser Asp Ser Phe Glu Asp Phe Trp Lys 1 5 10 15 Gly Glu Asp Leu Ser Asn Tyr Ser Tyr Ser Ser Thr Leu Pro Pro Phe 20 25 30 Leu Leu Asp Ala Ala Pro Cys Glu Pro Glu Ser Leu Glu Ile Asn Lys 35 40 45 Tyr Phe Val Val Ile Ile Tyr Ala Leu Val Phe Leu Leu Ser Leu Leu 50 55 60 Gly Asn Ser Leu Val Met Leu Val Ile Leu Tyr Ser Arg Val Gly Arg 65 70 75 80 Ser Val Thr Asp Val Tyr Leu Leu Asn Leu Ala Leu Ala Asp Leu Leu 85 90 95 Phe Ala Leu Thr Leu Pro Ile Trp Ala Ala Ser Lys Val Asn Gly Trp 100 105 110 Ile Phe Gly Thr Phe Leu Cys Lys Val Val Ser Leu Leu Lys Glu Val 115 120 125 Asn Phe Tyr Ser Gly Ile Leu Leu Leu Ala Cys Ile Ser Val Asp Arg 130 135 140 Tyr Leu Ala Ile Val His Ala Thr Arg Thr Leu Thr Gln Lys Arg Tyr 145 150 155 160 Leu Val Lys Phe Ile Cys Leu Ser Ile Trp Gly Leu Ser Leu Leu Leu 165 170 175 Ala Leu Pro Val Leu Leu Phe Arg Arg Thr Val Tyr Ser Ser Asn Val 180 185 190 Ser Pro Ala Cys Tyr Glu Asp Met Gly Asn Asn Thr Ala Asn Trp Arg 195 200 205 Met Leu Leu Arg Ile Leu Pro Gln Ser Phe Gly Phe Ile Val Pro Leu 210 215 220 Leu Ile Met Leu Phe Cys Tyr Gly Phe Thr Leu Arg Thr Leu Phe Lys 225 230 235 240 Ala His Met Gly Gln Lys His Arg Ala Met Arg Val Ile Phe Ala Val 245 250 255 Val Leu Ile Phe Leu Leu Cys Trp Leu Pro Tyr Asn Leu Val Leu Leu 260 265 270 Ala Asp Thr Leu Met Arg Thr Gln Val Ile Gln Glu Thr Cys Glu Arg 275 280 285 Arg Asn His Ile Asp Arg Ala Leu Asp Ala Thr Glu Ile Leu Gly Ile 290 295 300 Leu His Ser Cys Leu Asn Pro Leu Ile Tyr Ala Phe Ile Gly Gln Lys 305 310 315 320 Phe Arg His Gly Leu Leu Lys Ile Leu Ala Ile His Gly Leu Ile Ser 325 330 335 Lys Asp Ser Leu Pro Lys Asp Ser Arg Pro Ser Phe Val Gly Ser Ser 340 345 350 Ser Gly His Thr Ser Thr Thr Leu 355 360

1 SEQUENCE LISTING <160> NUMBER OF SEQ ID NOS: 110 <210> SEQ ID NO 1 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic construct <400> SEQUENCE: 1 accacagtcc atgccatcac 20 <210> SEQ ID NO 2 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic construct <400> SEQUENCE: 2 tccaccaccc tgttgctgta 20 <210> SEQ ID NO 3 <211> LENGTH: 22 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic construct <400> SEQUENCE: 3 tcctgatttc tgcagctctg tg 22 <210> SEQ ID NO 4 <211> LENGTH: 22 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic construct <400> SEQUENCE: 4 tgcttgaagt ttcactggca tc 22 <210> SEQ ID NO 5 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic construct <400> SEQUENCE: 5 gagccccgaa tctgacatta 20 <210> SEQ ID NO 6 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic construct <400> SEQUENCE: 6 gcagacactg caacacacct 20 <210> SEQ ID NO 7 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic construct <400> SEQUENCE: 7 attctgggca tccttcacag 20 <210> SEQ ID NO 8 <211> LENGTH: 20 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic construct <400> SEQUENCE: 8 tgcacttagg caggaggtct 20 <210> SEQ ID NO 9 <211> LENGTH: 403 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 9 Met Thr Ala Ile Ile Lys Glu Ile Val Ser Arg Asn Lys Arg Arg Tyr 1 5 10 15 Gln Glu Asp Gly Phe Asp Leu Asp Leu Thr Tyr Ile Tyr Pro Asn Ile 20 25 30 Ile Ala Met Gly Phe Pro Ala Glu Arg Leu Glu Gly Val Tyr Arg Asn 35 40 45 Asn Ile Asp Asp Val Val Arg Phe Leu Asp Ser Lys His Lys Asn His 50 55 60 Tyr Lys Ile Tyr Asn Leu Cys Ala Glu Arg His Tyr Asp Thr Ala Lys 65 70 75 80 Phe Asn Cys Arg Val Ala Gln Tyr Pro Phe Glu Asp His Asn Pro Pro 85 90 95 Gln Leu Glu Leu Ile Lys Pro Phe Cys Glu Asp Leu Asp Gln Trp Leu 100 105 110 Ser Glu Asp Asp Asn His Val Ala Ala Ile His Cys Lys Ala Gly Lys 115 120 125 Gly Arg Thr Gly Val Met Ile Cys Ala Tyr Leu Leu His Arg Gly Lys 130 135 140 Phe Leu Lys Ala Gln Glu Ala Leu Asp Phe Tyr Gly Glu Val Arg Thr 145 150 155 160 Arg Asp Lys Lys Gly Val Thr Ile Pro Ser Gln Arg Arg Tyr Val Tyr 165 170 175 Tyr Tyr Ser Tyr Leu Leu Lys Asn His Leu Asp Tyr Arg Pro Val Ala 180 185 190 Leu Leu Phe His Lys Met Met Phe Glu Thr Ile Pro Met Phe Ser Gly 195 200 205 Gly Thr Cys Asn Pro Gln Phe Val Val Cys Gln Leu Lys Val Lys Ile 210 215 220 Tyr Ser Ser Asn Ser Gly Pro Thr Arg Arg Glu Asp Lys Phe Met Tyr 225 230 235 240 Phe Glu Phe Pro Gln Pro Leu Pro Val Cys Gly Asp Ile Lys Val Glu 245 250 255 Phe Phe His Lys Gln Asn Lys Met Leu Lys Lys Asp Lys Met Phe His 260 265 270 Phe Trp Val Asn Thr Phe Phe Ile Pro Gly Pro Glu Glu Thr Ser Glu 275 280 285 Lys Val Glu Asn Gly Ser Leu Cys Asp Gln Glu Ile Asp Ser Ile Cys 290 295 300 Ser Ile Glu Arg Ala Asp Asn Asp Lys Glu Tyr Leu Val Leu Thr Leu 305 310 315 320 Thr Lys Asn Asp Leu Asp Lys Ala Asn Lys Asp Lys Ala Asn Arg Tyr 325 330 335 Phe Ser Pro Asn Phe Lys Val Lys Leu Tyr Phe Thr Lys Thr Val Glu 340 345 350 Glu Pro Ser Asn Pro Glu Ala Ser Ser Ser Thr Ser Val Thr Pro Asp 355 360 365 Val Ser Asp Asn Glu Pro Asp His Tyr Arg Tyr Ser Asp Thr Thr Asp 370 375 380 Ser Asp Pro Glu Asn Glu Pro Phe Asp Glu Asp Gln His Thr Gln Ile 385 390 395 400 Thr Lys Val <210> SEQ ID NO 10 <211> LENGTH: 375 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 10 Met Asp Ala Leu Gln Leu Ala Asn Ser Ala Phe Ala Val Asp Leu Phe 1 5 10 15 Lys Gln Leu Cys Glu Lys Glu Pro Leu Gly Asn Val Leu Phe Ser Pro 20 25 30 Ile Cys Leu Ser Thr Ser Leu Ser Leu Ala Gln Val Gly Ala Lys Gly 35 40 45 Asp Thr Ala Asn Glu Ile Gly Gln Val Leu His Phe Glu Asn Val Lys 50 55 60 Asp Val Pro Phe Gly Phe Gln Thr Val Thr Ser Asp Val Asn Lys Leu 65 70 75 80 Ser Ser Phe Tyr Ser Leu Lys Leu Ile Lys Arg Leu Tyr Val Asp Lys 85 90 95 Ser Leu Asn Leu Ser Thr Glu Phe Ile Ser Ser Thr Lys Arg Pro Tyr 100 105 110 Ala Lys Glu Leu Glu Thr Val Asp Phe Lys Asp Lys Leu Glu Glu Thr 115 120 125 Lys Gly Gln Ile Asn Asn Ser Ile Lys Asp Leu Thr Asp Gly His Phe 130 135 140 Glu Asn Ile Leu Ala Asp Asn Ser Val Asn Asp Gln Thr Lys Ile Leu 145 150 155 160 Val Val Asn Ala Ala Tyr Phe Val Gly Lys Trp Met Lys Lys Phe Ser 165 170 175 Glu Ser Glu Thr Lys Glu Cys Pro Phe Arg Val Asn Lys Thr Asp Thr 180 185 190 Lys Pro Val Gln Met Met Asn Met Glu Ala Thr Phe Cys Met Gly Asn 195 200 205 Ile Asp Ser Ile Asn Cys Lys Ile Ile Glu Leu Pro Phe Gln Asn Lys 210 215 220 His Leu Ser Met Phe Ile Leu Leu Pro Lys Asp Val Glu Asp Glu Ser 225 230 235 240 Thr Gly Leu Glu Lys Ile Glu Lys Gln Leu Asn Ser Glu Ser Leu Ser 245 250 255 Gln Trp Thr Asn Pro Ser Thr Met Ala Asn Ala Lys Val Lys Leu Ser 260 265 270 Ile Pro Lys Phe Lys Val Glu Lys Met Ile Asp Pro Lys Ala Cys Leu 275 280 285 Glu Asn Leu Gly Leu Lys His Ile Phe Ser Glu Asp Thr Ser Asp Phe 290 295 300

Ser Gly Met Ser Glu Thr Lys Gly Val Ala Leu Ser Asn Val Ile His 305 310 315 320 Lys Val Cys Leu Glu Ile Thr Glu Asp Gly Gly Asp Ser Ile Glu Val 325 330 335 Pro Gly Ala Arg Ile Leu Gln His Lys Asp Glu Leu Asn Ala Asp His 340 345 350 Pro Phe Ile Tyr Ile Ile Arg His Asn Lys Thr Arg Asn Ile Ile Phe 355 360 365 Phe Gly Lys Phe Cys Ser Pro 370 375 <210> SEQ ID NO 11 <211> LENGTH: 429 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 11 Met Ala Ser Asn Ser Ile Phe Asp Ser Phe Pro Thr Tyr Ser Pro Thr 1 5 10 15 Phe Ile Arg Asp Pro Ser Thr Ser Arg Arg Phe Thr Pro Pro Ser Pro 20 25 30 Ala Phe Pro Cys Gly Gly Gly Gly Gly Lys Met Gly Glu Asn Ser Gly 35 40 45 Ala Leu Ser Ala Gln Ala Ala Val Gly Pro Gly Gly Arg Ala Arg Pro 50 55 60 Glu Val Arg Ser Met Val Asp Val Leu Ala Asp His Ala Gly Glu Leu 65 70 75 80 Val Arg Thr Asp Ser Pro Asn Phe Leu Cys Ser Val Leu Pro Ser His 85 90 95 Trp Arg Cys Asn Lys Thr Leu Pro Val Ala Phe Lys Val Val Ala Leu 100 105 110 Gly Asp Val Pro Asp Gly Thr Val Val Thr Val Met Ala Gly Asn Asp 115 120 125 Glu Asn Tyr Ser Ala Glu Leu Arg Asn Ala Ser Ala Val Met Lys Asn 130 135 140 Gln Val Ala Arg Phe Asn Asp Leu Arg Phe Val Gly Arg Ser Gly Arg 145 150 155 160 Gly Lys Ser Phe Thr Leu Thr Ile Thr Val Phe Thr Asn Pro Thr Gln 165 170 175 Val Ala Thr Tyr His Arg Ala Ile Lys Val Thr Val Asp Gly Pro Arg 180 185 190 Glu Pro Arg Arg His Arg Gln Lys Leu Glu Asp Gln Thr Lys Pro Phe 195 200 205 Pro Asp Arg Phe Gly Asp Leu Glu Arg Leu Arg Met Arg Val Thr Pro 210 215 220 Ser Thr Pro Ser Pro Arg Gly Ser Leu Ser Thr Thr Ser His Phe Ser 225 230 235 240 Ser Gln Pro Gln Thr Pro Ile Gln Gly Thr Ser Glu Leu Asn Pro Phe 245 250 255 Ser Asp Pro Arg Gln Phe Asp Arg Ser Phe Pro Thr Leu Pro Thr Leu 260 265 270 Thr Glu Ser Arg Phe Pro Asp Pro Arg Met His Tyr Pro Gly Ala Met 275 280 285 Ser Ala Ala Phe Pro Tyr Ser Ala Thr Pro Ser Gly Thr Ser Ile Ser 290 295 300 Ser Leu Ser Val Ala Gly Met Pro Ala Thr Ser Arg Phe His His Thr 305 310 315 320 Tyr Leu Pro Pro Pro Tyr Pro Gly Ala Pro Gln Asn Gln Ser Gly Pro 325 330 335 Phe Gln Ala Asn Pro Ser Pro Tyr His Leu Tyr Tyr Gly Thr Ser Ser 340 345 350 Gly Ser Tyr Gln Phe Ser Met Val Ala Gly Ser Ser Ser Gly Gly Asp 355 360 365 Arg Ser Pro Thr Arg Met Leu Ala Ser Cys Thr Ser Ser Ala Ala Ser 370 375 380 Val Ala Ala Gly Asn Leu Met Asn Pro Ser Leu Gly Gly Gln Ser Asp 385 390 395 400 Gly Val Glu Ala Asp Gly Ser His Ser Asn Ser Pro Thr Ala Leu Ser 405 410 415 Thr Pro Gly Arg Met Asp Glu Ala Val Trp Arg Pro Tyr 420 425 <210> SEQ ID NO 12 <211> LENGTH: 415 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 12 Met Arg Ile Pro Val Asp Pro Ser Thr Ser Arg Arg Phe Thr Pro Pro 1 5 10 15 Ser Pro Ala Phe Pro Cys Gly Gly Gly Gly Gly Lys Met Gly Glu Asn 20 25 30 Ser Gly Ala Leu Ser Ala Gln Ala Ala Val Gly Pro Gly Gly Arg Ala 35 40 45 Arg Pro Glu Val Arg Ser Met Val Asp Val Leu Ala Asp His Ala Gly 50 55 60 Glu Leu Val Arg Thr Asp Ser Pro Asn Phe Leu Cys Ser Val Leu Pro 65 70 75 80 Ser His Trp Arg Cys Asn Lys Thr Leu Pro Val Ala Phe Lys Val Val 85 90 95 Ala Leu Gly Asp Val Pro Asp Gly Thr Val Val Thr Val Met Ala Gly 100 105 110 Asn Asp Glu Asn Tyr Ser Ala Glu Leu Arg Asn Ala Ser Ala Val Met 115 120 125 Lys Asn Gln Val Ala Arg Phe Asn Asp Leu Arg Phe Val Gly Arg Ser 130 135 140 Gly Arg Gly Lys Ser Phe Thr Leu Thr Ile Thr Val Phe Thr Asn Pro 145 150 155 160 Thr Gln Val Ala Thr Tyr His Arg Ala Ile Lys Val Thr Val Asp Gly 165 170 175 Pro Arg Glu Pro Arg Arg His Arg Gln Lys Leu Glu Asp Gln Thr Lys 180 185 190 Pro Phe Pro Asp Arg Phe Gly Asp Leu Glu Arg Leu Arg Met Arg Val 195 200 205 Thr Pro Ser Thr Pro Ser Pro Arg Gly Ser Leu Ser Thr Thr Ser His 210 215 220 Phe Ser Ser Gln Pro Gln Thr Pro Ile Gln Gly Thr Ser Glu Leu Asn 225 230 235 240 Pro Phe Ser Asp Pro Arg Gln Phe Asp Arg Ser Phe Pro Thr Leu Pro 245 250 255 Thr Leu Thr Glu Ser Arg Phe Pro Asp Pro Arg Met His Tyr Pro Gly 260 265 270 Ala Met Ser Ala Ala Phe Pro Tyr Ser Ala Thr Pro Ser Gly Thr Ser 275 280 285 Ile Ser Ser Leu Ser Val Ala Gly Met Pro Ala Thr Ser Arg Phe His 290 295 300 His Thr Tyr Leu Pro Pro Pro Tyr Pro Gly Ala Pro Gln Asn Gln Ser 305 310 315 320 Gly Pro Phe Gln Ala Asn Pro Ser Pro Tyr His Leu Tyr Tyr Gly Thr 325 330 335 Ser Ser Gly Ser Tyr Gln Phe Ser Met Val Ala Gly Ser Ser Ser Gly 340 345 350 Gly Asp Arg Ser Pro Thr Arg Met Leu Ala Ser Cys Thr Ser Ser Ala 355 360 365 Ala Ser Val Ala Ala Gly Asn Leu Met Asn Pro Ser Leu Gly Gly Gln 370 375 380 Ser Asp Gly Val Glu Ala Asp Gly Ser His Ser Asn Ser Pro Thr Ala 385 390 395 400 Leu Ser Thr Pro Gly Arg Met Asp Glu Ala Val Trp Arg Pro Tyr 405 410 415 <210> SEQ ID NO 13 <211> LENGTH: 178 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 13 Met Ser Gly Gly Lys Tyr Val Asp Ser Glu Gly His Leu Tyr Thr Val 1 5 10 15 Pro Ile Arg Glu Gln Gly Asn Ile Tyr Lys Pro Asn Asn Lys Ala Met 20 25 30 Ala Asp Glu Leu Ser Glu Lys Gln Val Tyr Asp Ala His Thr Lys Glu 35 40 45 Ile Asp Leu Val Asn Arg Asp Pro Lys His Leu Asn Asp Asp Val Val 50 55 60 Lys Ile Asp Phe Glu Asp Val Ile Ala Glu Pro Glu Gly Thr His Ser 65 70 75 80 Phe Asp Gly Ile Trp Lys Ala Ser Phe Thr Thr Phe Thr Val Thr Lys 85 90 95 Tyr Trp Phe Tyr Arg Leu Leu Ser Ala Leu Phe Gly Ile Pro Met Ala 100 105 110 Leu Ile Trp Gly Ile Tyr Phe Ala Ile Leu Ser Phe Leu His Ile Trp 115 120 125 Ala Val Val Pro Cys Ile Lys Ser Phe Leu Ile Glu Ile Gln Cys Ile 130 135 140 Ser Arg Val Tyr Ser Ile Tyr Val His Thr Val Cys Asp Pro Leu Phe 145 150 155 160 Glu Ala Val Gly Lys Ile Phe Ser Asn Val Arg Ile Asn Leu Gln Lys 165 170 175 Glu Ile <210> SEQ ID NO 14 <211> LENGTH: 177 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 14 Met Val Leu Leu Ser Thr Leu Gly Ile Val Phe Gln Gly Glu Gly Pro 1 5 10 15 Pro Ile Ser Ser Cys Asp Thr Gly Thr Met Ala Asn Cys Glu Arg Thr 20 25 30 Phe Ile Ala Ile Lys Pro Asp Gly Val Gln Arg Gly Leu Val Gly Glu 35 40 45

Ile Ile Lys Arg Phe Glu Gln Lys Gly Phe Arg Leu Val Gly Leu Lys 50 55 60 Phe Met Gln Ala Ser Glu Asp Leu Leu Lys Glu His Tyr Val Asp Leu 65 70 75 80 Lys Asp Arg Pro Phe Phe Ala Gly Leu Val Lys Tyr Met His Ser Gly 85 90 95 Pro Val Val Ala Met Val Trp Glu Gly Leu Asn Val Val Lys Thr Gly 100 105 110 Arg Val Met Leu Gly Glu Thr Asn Pro Ala Asp Ser Lys Pro Gly Thr 115 120 125 Ile Arg Gly Asp Phe Cys Ile Gln Val Gly Arg Asn Ile Ile His Gly 130 135 140 Ser Asp Ser Val Glu Ser Ala Glu Lys Glu Ile Gly Leu Trp Phe His 145 150 155 160 Pro Glu Glu Leu Val Asp Tyr Thr Ser Cys Ala Gln Asn Trp Ile Tyr 165 170 175 Glu <210> SEQ ID NO 15 <211> LENGTH: 152 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 15 Met Ala Asn Cys Glu Arg Thr Phe Ile Ala Ile Lys Pro Asp Gly Val 1 5 10 15 Gln Arg Gly Leu Val Gly Glu Ile Ile Lys Arg Phe Glu Gln Lys Gly 20 25 30 Phe Arg Leu Val Gly Leu Lys Phe Met Gln Ala Ser Glu Asp Leu Leu 35 40 45 Lys Glu His Tyr Val Asp Leu Lys Asp Arg Pro Phe Phe Ala Gly Leu 50 55 60 Val Lys Tyr Met His Ser Gly Pro Val Val Ala Met Val Trp Glu Gly 65 70 75 80 Leu Asn Val Val Lys Thr Gly Arg Val Met Leu Gly Glu Thr Asn Pro 85 90 95 Ala Asp Ser Lys Pro Gly Thr Ile Arg Gly Asp Phe Cys Ile Gln Val 100 105 110 Gly Arg Asn Ile Ile His Gly Ser Asp Ser Val Glu Ser Ala Glu Lys 115 120 125 Glu Ile Gly Leu Trp Phe His Pro Glu Glu Leu Val Asp Tyr Thr Ser 130 135 140 Cys Ala Gln Asn Trp Ile Tyr Glu 145 150 <210> SEQ ID NO 16 <211> LENGTH: 928 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 16 Met Pro Pro Lys Thr Pro Arg Lys Thr Ala Ala Thr Ala Ala Ala Ala 1 5 10 15 Ala Ala Glu Pro Pro Ala Pro Pro Pro Pro Pro Pro Pro Glu Glu Asp 20 25 30 Pro Glu Gln Asp Ser Gly Pro Glu Asp Leu Pro Leu Val Arg Leu Glu 35 40 45 Phe Glu Glu Thr Glu Glu Pro Asp Phe Thr Ala Leu Cys Gln Lys Leu 50 55 60 Lys Ile Pro Asp His Val Arg Glu Arg Ala Trp Leu Thr Trp Glu Lys 65 70 75 80 Val Ser Ser Val Asp Gly Val Leu Gly Gly Tyr Ile Gln Lys Lys Lys 85 90 95 Glu Leu Trp Gly Ile Cys Ile Phe Ile Ala Ala Val Asp Leu Asp Glu 100 105 110 Met Ser Phe Thr Phe Thr Glu Leu Gln Lys Asn Ile Glu Ile Ser Val 115 120 125 His Lys Phe Phe Asn Leu Leu Lys Glu Ile Asp Thr Ser Thr Lys Val 130 135 140 Asp Asn Ala Met Ser Arg Leu Leu Lys Lys Tyr Asp Val Leu Phe Ala 145 150 155 160 Leu Phe Ser Lys Leu Glu Arg Thr Cys Glu Leu Ile Tyr Leu Thr Gln 165 170 175 Pro Ser Ser Ser Ile Ser Thr Glu Ile Asn Ser Ala Leu Val Leu Lys 180 185 190 Val Ser Trp Ile Thr Phe Leu Leu Ala Lys Gly Glu Val Leu Gln Met 195 200 205 Glu Asp Asp Leu Val Ile Ser Phe Gln Leu Met Leu Cys Val Leu Asp 210 215 220 Tyr Phe Ile Lys Leu Ser Pro Pro Met Leu Leu Lys Glu Pro Tyr Lys 225 230 235 240 Thr Ala Val Ile Pro Ile Asn Gly Ser Pro Arg Thr Pro Arg Arg Gly 245 250 255 Gln Asn Arg Ser Ala Arg Ile Ala Lys Gln Leu Glu Asn Asp Thr Arg 260 265 270 Ile Ile Glu Val Leu Cys Lys Glu His Glu Cys Asn Ile Asp Glu Val 275 280 285 Lys Asn Val Tyr Phe Lys Asn Phe Ile Pro Phe Met Asn Ser Leu Gly 290 295 300 Leu Val Thr Ser Asn Gly Leu Pro Glu Val Glu Asn Leu Ser Lys Arg 305 310 315 320 Tyr Glu Glu Ile Tyr Leu Lys Asn Lys Asp Leu Asp Ala Arg Leu Phe 325 330 335 Leu Asp His Asp Lys Thr Leu Gln Thr Asp Ser Ile Asp Ser Phe Glu 340 345 350 Thr Gln Arg Thr Pro Arg Lys Ser Asn Leu Asp Glu Glu Val Asn Val 355 360 365 Ile Pro Pro His Thr Pro Val Arg Thr Val Met Asn Thr Ile Gln Gln 370 375 380 Leu Met Met Ile Leu Asn Ser Ala Ser Asp Gln Pro Ser Glu Asn Leu 385 390 395 400 Ile Ser Tyr Phe Asn Asn Cys Thr Val Asn Pro Lys Glu Ser Ile Leu 405 410 415 Lys Arg Val Lys Asp Ile Gly Tyr Ile Phe Lys Glu Lys Phe Ala Lys 420 425 430 Ala Val Gly Gln Gly Cys Val Glu Ile Gly Ser Gln Arg Tyr Lys Leu 435 440 445 Gly Val Arg Leu Tyr Tyr Arg Val Met Glu Ser Met Leu Lys Ser Glu 450 455 460 Glu Glu Arg Leu Ser Ile Gln Asn Phe Ser Lys Leu Leu Asn Asp Asn 465 470 475 480 Ile Phe His Met Ser Leu Leu Ala Cys Ala Leu Glu Val Val Met Ala 485 490 495 Thr Tyr Ser Arg Ser Thr Ser Gln Asn Leu Asp Ser Gly Thr Asp Leu 500 505 510 Ser Phe Pro Trp Ile Leu Asn Val Leu Asn Leu Lys Ala Phe Asp Phe 515 520 525 Tyr Lys Val Ile Glu Ser Phe Ile Lys Ala Glu Gly Asn Leu Thr Arg 530 535 540 Glu Met Ile Lys His Leu Glu Arg Cys Glu His Arg Ile Met Glu Ser 545 550 555 560 Leu Ala Trp Leu Ser Asp Ser Pro Leu Phe Asp Leu Ile Lys Gln Ser 565 570 575 Lys Asp Arg Glu Gly Pro Thr Asp His Leu Glu Ser Ala Cys Pro Leu 580 585 590 Asn Leu Pro Leu Gln Asn Asn His Thr Ala Ala Asp Met Tyr Leu Ser 595 600 605 Pro Val Arg Ser Pro Lys Lys Lys Gly Ser Thr Thr Arg Val Asn Ser 610 615 620 Thr Ala Asn Ala Glu Thr Gln Ala Thr Ser Ala Phe Gln Thr Gln Lys 625 630 635 640 Pro Leu Lys Ser Thr Ser Leu Ser Leu Phe Tyr Lys Lys Val Tyr Arg 645 650 655 Leu Ala Tyr Leu Arg Leu Asn Thr Leu Cys Glu Arg Leu Leu Ser Glu 660 665 670 His Pro Glu Leu Glu His Ile Ile Trp Thr Leu Phe Gln His Thr Leu 675 680 685 Gln Asn Glu Tyr Glu Leu Met Arg Asp Arg His Leu Asp Gln Ile Met 690 695 700 Met Cys Ser Met Tyr Gly Ile Cys Lys Val Lys Asn Ile Asp Leu Lys 705 710 715 720 Phe Lys Ile Ile Val Thr Ala Tyr Lys Asp Leu Pro His Ala Val Gln 725 730 735 Glu Thr Phe Lys Arg Val Leu Ile Lys Glu Glu Glu Tyr Asp Ser Ile 740 745 750 Ile Val Phe Tyr Asn Ser Val Phe Met Gln Arg Leu Lys Thr Asn Ile 755 760 765 Leu Gln Tyr Ala Ser Thr Arg Pro Pro Thr Leu Ser Pro Ile Pro His 770 775 780 Ile Pro Arg Ser Pro Tyr Lys Phe Pro Ser Ser Pro Leu Arg Ile Pro 785 790 795 800 Gly Gly Asn Ile Tyr Ile Ser Pro Leu Lys Ser Pro Tyr Lys Ile Ser 805 810 815 Glu Gly Leu Pro Thr Pro Thr Lys Met Thr Pro Arg Ser Arg Ile Leu 820 825 830 Val Ser Ile Gly Glu Ser Phe Gly Thr Ser Glu Lys Phe Gln Lys Ile 835 840 845 Asn Gln Met Val Cys Asn Ser Asp Arg Val Leu Lys Arg Ser Ala Glu 850 855 860 Gly Ser Asn Pro Pro Lys Pro Leu Lys Lys Leu Arg Phe Asp Ile Glu 865 870 875 880 Gly Ser Asp Glu Ala Asp Gly Ser Lys His Leu Pro Gly Glu Ser Lys 885 890 895 Phe Gln Gln Lys Leu Ala Glu Met Thr Ser Thr Arg Thr Arg Met Gln 900 905 910 Lys Gln Lys Met Asn Asp Ser Met Asp Thr Ser Asn Lys Glu Glu Lys 915 920 925 <210> SEQ ID NO 17 <211> LENGTH: 1043 <212> TYPE: PRT <213> ORGANISM: Homo sapiens

<400> SEQUENCE: 17 Met Pro Leu Leu Glu Gly Ser Val Gly Val Glu Asp Leu Val Leu Leu 1 5 10 15 Glu Pro Leu Val Glu Glu Ser Leu Leu Lys Asn Leu Gln Leu Arg Tyr 20 25 30 Glu Asn Lys Glu Ile Tyr Thr Tyr Ile Gly Asn Val Val Ile Ser Val 35 40 45 Asn Pro Tyr Gln Gln Leu Pro Ile Tyr Gly Pro Glu Phe Ile Ala Lys 50 55 60 Tyr Gln Asp Tyr Thr Phe Tyr Glu Leu Lys Pro His Ile Tyr Ala Leu 65 70 75 80 Ala Asn Val Ala Tyr Gln Ser Leu Arg Asp Arg Asp Arg Asp Gln Cys 85 90 95 Ile Leu Ile Thr Gly Glu Ser Gly Ser Gly Lys Thr Glu Ala Ser Lys 100 105 110 Leu Val Met Ser Tyr Val Ala Ala Val Cys Gly Lys Gly Glu Gln Val 115 120 125 Asn Ser Val Lys Glu Gln Leu Leu Gln Ser Asn Pro Val Leu Glu Ala 130 135 140 Phe Gly Asn Ala Lys Thr Ile Arg Asn Asn Asn Ser Ser Arg Phe Gly 145 150 155 160 Lys Tyr Met Asp Ile Glu Phe Asp Phe Lys Gly Ser Pro Leu Gly Gly 165 170 175 Val Ile Thr Asn Tyr Leu Leu Glu Lys Ser Arg Leu Val Lys Gln Leu 180 185 190 Lys Gly Glu Arg Asn Phe His Ile Phe Tyr Gln Leu Leu Ala Gly Ala 195 200 205 Asp Glu Gln Leu Leu Lys Ala Leu Lys Leu Glu Arg Asp Thr Thr Gly 210 215 220 Tyr Ala Tyr Leu Asn His Glu Val Ser Arg Val Asp Gly Met Asp Asp 225 230 235 240 Ala Ser Ser Phe Arg Ala Val Gln Ser Ala Met Ala Val Ile Gly Phe 245 250 255 Ser Glu Glu Glu Ile Arg Gln Val Leu Glu Val Thr Ser Met Val Leu 260 265 270 Lys Leu Gly Asn Val Leu Val Ala Asp Glu Phe Gln Ala Ser Gly Ile 275 280 285 Pro Ala Ser Gly Ile Arg Asp Gly Arg Gly Val Arg Glu Ile Gly Glu 290 295 300 Met Val Gly Leu Asn Ser Glu Glu Val Glu Arg Ala Leu Cys Ser Arg 305 310 315 320 Thr Met Glu Thr Ala Lys Glu Lys Val Val Thr Ala Leu Asn Val Met 325 330 335 Gln Ala Gln Tyr Ala Arg Asp Ala Leu Ala Lys Asn Ile Tyr Ser Arg 340 345 350 Leu Phe Asp Trp Ile Val Asn Arg Ile Asn Glu Ser Ile Lys Val Gly 355 360 365 Ile Gly Glu Lys Lys Lys Val Met Gly Val Leu Asp Ile Tyr Gly Phe 370 375 380 Glu Ile Leu Glu Asp Asn Ser Phe Glu Gln Phe Val Ile Asn Tyr Cys 385 390 395 400 Asn Glu Lys Leu Gln Gln Val Phe Ile Glu Met Thr Leu Lys Glu Glu 405 410 415 Gln Glu Glu Tyr Lys Arg Glu Gly Ile Pro Trp Thr Lys Val Asp Tyr 420 425 430 Phe Asp Asn Gly Ile Ile Cys Lys Leu Ile Glu His Asn Gln Arg Gly 435 440 445 Ile Leu Ala Met Leu Asp Glu Glu Cys Leu Arg Pro Gly Val Val Ser 450 455 460 Asp Ser Thr Phe Leu Ala Lys Leu Asn Gln Leu Phe Ser Lys His Gly 465 470 475 480 His Tyr Glu Ser Lys Val Thr Gln Asn Ala Gln Arg Gln Tyr Asp His 485 490 495 Thr Met Gly Leu Ser Cys Phe Arg Ile Cys His Tyr Ala Gly Lys Val 500 505 510 Thr Tyr Asn Val Thr Ser Phe Ile Asp Lys Asn Asn Asp Leu Leu Phe 515 520 525 Arg Asp Leu Leu Gln Ala Met Trp Lys Ala Gln His Pro Leu Leu Arg 530 535 540 Ser Leu Phe Pro Glu Gly Asn Pro Lys Gln Ala Ser Leu Lys Arg Pro 545 550 555 560 Pro Thr Ala Gly Ala Gln Phe Lys Ser Ser Val Ala Ile Leu Met Lys 565 570 575 Asn Leu Tyr Ser Lys Ser Pro Asn Tyr Ile Arg Cys Ile Lys Pro Asn 580 585 590 Glu His Gln Gln Arg Gly Gln Phe Ser Ser Asp Leu Val Ala Thr Gln 595 600 605 Ala Arg Tyr Leu Gly Leu Leu Glu Asn Val Arg Val Arg Arg Ala Gly 610 615 620 Tyr Ala His Arg Gln Gly Tyr Gly Pro Phe Leu Glu Arg Tyr Arg Leu 625 630 635 640 Leu Ser Arg Ser Thr Trp Pro His Trp Asn Gly Gly Asp Arg Glu Gly 645 650 655 Val Glu Lys Val Leu Gly Glu Leu Ser Met Ser Ser Gly Glu Leu Ala 660 665 670 Phe Gly Lys Thr Lys Ile Phe Ile Arg Ser Pro Lys Thr Leu Phe Tyr 675 680 685 Leu Glu Glu Gln Arg Arg Leu Arg Leu Gln Gln Leu Ala Thr Leu Ile 690 695 700 Gln Lys Ile Tyr Arg Gly Trp Arg Cys Arg Thr His Tyr Gln Leu Met 705 710 715 720 Arg Lys Ser Gln Ile Leu Ile Ser Ser Trp Phe Arg Gly Asn Met Gln 725 730 735 Lys Lys Cys Tyr Gly Lys Ile Lys Ala Ser Val Leu Leu Ile Gln Ala 740 745 750 Phe Val Arg Gly Trp Lys Ala Arg Lys Asn Tyr Arg Lys Tyr Phe Arg 755 760 765 Ser Glu Ala Ala Leu Thr Leu Ala Asp Phe Ile Tyr Lys Ser Met Val 770 775 780 Gln Lys Phe Leu Leu Gly Leu Lys Asn Asn Leu Pro Ser Thr Asn Val 785 790 795 800 Leu Asp Lys Thr Trp Pro Ala Ala Pro Tyr Lys Cys Leu Ser Thr Ala 805 810 815 Asn Gln Glu Leu Gln Gln Leu Phe Tyr Gln Trp Lys Cys Lys Arg Phe 820 825 830 Arg Asp Gln Leu Ser Pro Lys Gln Val Glu Ile Leu Arg Glu Lys Leu 835 840 845 Cys Ala Ser Glu Leu Phe Lys Gly Lys Lys Ala Ser Tyr Pro Gln Ser 850 855 860 Val Pro Ile Pro Phe Cys Gly Asp Tyr Ile Gly Leu Gln Gly Asn Pro 865 870 875 880 Lys Leu Gln Lys Leu Lys Gly Gly Glu Glu Gly Pro Val Leu Met Ala 885 890 895 Glu Ala Val Lys Lys Val Asn Arg Gly Asn Gly Lys Thr Ser Ser Arg 900 905 910 Ile Leu Leu Leu Thr Lys Gly His Val Ile Leu Thr Asp Thr Lys Lys 915 920 925 Ser Gln Ala Lys Ile Val Ile Gly Leu Asp Asn Val Ala Gly Val Ser 930 935 940 Val Thr Ser Leu Lys Asp Gly Leu Phe Ser Leu His Leu Ser Glu Met 945 950 955 960 Ser Ser Val Gly Ser Lys Gly Asp Phe Leu Leu Val Ser Glu His Val 965 970 975 Ile Glu Leu Leu Thr Lys Met Tyr Arg Ala Val Leu Asp Ala Thr Gln 980 985 990 Arg Gln Leu Thr Val Thr Val Thr Glu Lys Phe Ser Val Arg Phe Lys 995 1000 1005 Glu Asn Ser Val Ala Val Lys Val Val Gln Gly Pro Ala Gly Gly Asp 1010 1015 1020 Asn Ser Lys Leu Arg Tyr Lys Lys Lys Gly Ser His Cys Leu Glu Val 1025 1030 1035 1040 Thr Val Gln <210> SEQ ID NO 18 <211> LENGTH: 248 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 18 Met Ala Ala Gly Met Tyr Leu Glu His Tyr Leu Asp Ser Ile Glu Asn 1 5 10 15 Leu Pro Phe Glu Leu Gln Arg Asn Phe Gln Leu Met Arg Asp Leu Asp 20 25 30 Gln Arg Thr Glu Asp Leu Lys Ala Glu Ile Asp Lys Leu Ala Thr Glu 35 40 45 Tyr Met Ser Ser Ala Arg Ser Leu Ser Ser Glu Glu Lys Leu Ala Leu 50 55 60 Leu Lys Gln Ile Gln Glu Ala Tyr Gly Lys Cys Lys Glu Phe Gly Asp 65 70 75 80 Asp Lys Val Gln Leu Ala Met Gln Thr Tyr Glu Met Val Asp Lys His 85 90 95 Ile Arg Arg Leu Asp Thr Asp Leu Ala Arg Phe Glu Ala Asp Leu Lys 100 105 110 Glu Lys Gln Ile Glu Ser Ser Asp Tyr Asp Ser Ser Ser Ser Lys Gly 115 120 125 Lys Lys Ser Arg Thr Gln Lys Glu Lys Lys Ala Ala Arg Ala Arg Ser 130 135 140 Lys Gly Lys Asn Ser Asp Glu Glu Ala Pro Lys Thr Ala Gln Lys Lys 145 150 155 160 Leu Lys Leu Val Arg Thr Ser Pro Glu Tyr Gly Met Pro Ser Val Thr 165 170 175 Phe Gly Ser Val His Pro Ser Asp Val Leu Asp Met Pro Val Asp Pro 180 185 190 Asn Glu Pro Thr Tyr Cys Leu Cys His Gln Val Ser Tyr Gly Glu Met 195 200 205 Ile Gly Cys Asp Asn Pro Asp Cys Ser Ile Glu Trp Phe His Phe Ala 210 215 220 Cys Val Gly Leu Thr Thr Lys Pro Arg Gly Lys Trp Phe Cys Pro Arg

225 230 235 240 Cys Ser Gln Glu Arg Lys Lys Lys 245 <210> SEQ ID NO 19 <211> LENGTH: 246 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 19 Met Ala Ala Gly Met Tyr Leu Glu His Tyr Leu Asp Ser Ile Glu Asn 1 5 10 15 Leu Pro Phe Glu Leu Gln Arg Asn Phe Gln Leu Met Arg Asp Leu Asp 20 25 30 Gln Arg Thr Glu Asp Leu Lys Ala Glu Ile Asp Lys Leu Ala Thr Glu 35 40 45 Tyr Met Ser Ser Ala Arg Ser Leu Ser Ser Glu Glu Lys Leu Ala Leu 50 55 60 Leu Lys Gln Ile Gln Glu Ala Tyr Gly Lys Cys Lys Glu Phe Gly Asp 65 70 75 80 Asp Lys Val Gln Leu Ala Met Gln Thr Tyr Glu Met Val Asp Lys His 85 90 95 Ile Arg Arg Leu Asp Thr Asp Leu Ala Arg Phe Glu Ala Asp Leu Lys 100 105 110 Glu Lys Gln Ile Glu Ser Ser Asp Tyr Asp Ser Ser Ser Ser Lys Glu 115 120 125 Gly Arg Thr Gln Lys Glu Lys Lys Ala Ala Arg Ala Arg Ser Lys Gly 130 135 140 Lys Asn Ser Asp Glu Glu Ala Pro Lys Thr Ala Gln Lys Lys Leu Lys 145 150 155 160 Leu Val Arg Thr Ser Pro Glu Tyr Gly Met Pro Ser Val Thr Phe Gly 165 170 175 Ser Val His Pro Ser Asp Val Leu Asp Met Pro Val Asp Pro Asn Glu 180 185 190 Pro Thr Tyr Cys Leu Cys His Gln Val Ser Tyr Gly Glu Met Ile Gly 195 200 205 Cys Asp Asn Pro Asp Cys Ser Ile Glu Trp Phe His Phe Ala Cys Val 210 215 220 Gly Leu Thr Thr Lys Pro Arg Gly Lys Trp Phe Cys Pro Arg Cys Ser 225 230 235 240 Gln Glu Arg Lys Lys Lys 245 <210> SEQ ID NO 20 <211> LENGTH: 245 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 20 Met Ala Ala Gly Met Tyr Leu Glu His Tyr Leu Asp Ser Ile Glu Asn 1 5 10 15 Leu Pro Phe Glu Leu Gln Arg Asn Phe Gln Leu Met Arg Asp Leu Asp 20 25 30 Gln Arg Thr Glu Asp Leu Lys Ala Glu Ile Asp Lys Leu Ala Thr Glu 35 40 45 Tyr Met Ser Ser Ala Arg Ser Leu Ser Ser Glu Glu Lys Leu Ala Leu 50 55 60 Leu Lys Gln Ile Gln Glu Ala Tyr Gly Lys Cys Lys Glu Phe Gly Asp 65 70 75 80 Asp Lys Val Gln Leu Ala Met Gln Thr Tyr Glu Met Val Asp Lys His 85 90 95 Ile Arg Arg Leu Asp Thr Asp Leu Ala Arg Phe Glu Ala Asp Leu Lys 100 105 110 Glu Lys Gln Ile Glu Ser Ser Asp Tyr Asp Ser Ser Ser Ser Lys Gly 115 120 125 Arg Thr Gln Lys Glu Lys Lys Ala Ala Arg Ala Arg Ser Lys Gly Lys 130 135 140 Asn Ser Asp Glu Glu Ala Pro Lys Thr Ala Gln Lys Lys Leu Lys Leu 145 150 155 160 Val Arg Thr Ser Pro Glu Tyr Gly Met Pro Ser Val Thr Phe Gly Ser 165 170 175 Val His Pro Ser Asp Val Leu Asp Met Pro Val Asp Pro Asn Glu Pro 180 185 190 Thr Tyr Cys Leu Cys His Gln Val Ser Tyr Gly Glu Met Ile Gly Cys 195 200 205 Asp Asn Pro Asp Cys Ser Ile Glu Trp Phe His Phe Ala Cys Val Gly 210 215 220 Leu Thr Thr Lys Pro Arg Gly Lys Trp Phe Cys Pro Arg Cys Ser Gln 225 230 235 240 Glu Arg Lys Lys Lys 245 <210> SEQ ID NO 21 <211> LENGTH: 225 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 21 Met Ala Ala Gly Met Tyr Leu Glu His Tyr Leu Asp Asn Leu Lys Ala 1 5 10 15 Glu Ile Asp Lys Leu Ala Thr Glu Tyr Met Ser Ser Ala Arg Ser Leu 20 25 30 Ser Ser Glu Glu Lys Leu Ala Leu Leu Lys Gln Ile Gln Glu Ala Tyr 35 40 45 Gly Lys Cys Lys Glu Phe Gly Asp Asp Lys Val Gln Leu Ala Met Gln 50 55 60 Thr Tyr Glu Met Val Asp Lys His Ile Arg Arg Leu Asp Thr Asp Leu 65 70 75 80 Ala Arg Phe Glu Ala Asp Leu Lys Glu Lys Gln Ile Glu Ser Ser Asp 85 90 95 Tyr Asp Ser Ser Ser Ser Lys Gly Lys Lys Lys Gly Arg Thr Gln Lys 100 105 110 Glu Lys Lys Ala Ala Arg Ala Arg Ser Lys Gly Lys Asn Ser Asp Glu 115 120 125 Glu Ala Pro Lys Thr Ala Gln Lys Lys Leu Lys Leu Val Arg Thr Ser 130 135 140 Pro Glu Tyr Gly Met Pro Ser Val Thr Phe Gly Ser Val His Pro Ser 145 150 155 160 Asp Val Leu Asp Met Pro Val Asp Pro Asn Glu Pro Thr Tyr Cys Leu 165 170 175 Cys His Gln Val Ser Tyr Gly Glu Met Ile Gly Cys Asp Asn Pro Asp 180 185 190 Cys Ser Ile Glu Trp Phe His Phe Ala Cys Val Gly Leu Thr Thr Lys 195 200 205 Pro Arg Gly Lys Trp Phe Cys Pro Arg Cys Ser Gln Glu Arg Lys Lys 210 215 220 Lys 225 <210> SEQ ID NO 22 <211> LENGTH: 179 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 22 Met Ala Ala Gly Met Tyr Leu Glu His Tyr Leu Asp Ser Ile Glu Asn 1 5 10 15 Leu Pro Phe Glu Leu Gln Arg Asn Phe Gln Leu Met Arg Asp Leu Asp 20 25 30 Gln Arg Thr Glu Asp Leu Lys Ala Glu Ile Asp Lys Leu Ala Thr Glu 35 40 45 Tyr Met Ser Ser Ala Arg Ser Leu Ser Ser Glu Glu Lys Leu Ala Leu 50 55 60 Leu Lys Gln Ile Gln Glu Ala Tyr Gly Lys Cys Lys Glu Phe Gly Asp 65 70 75 80 Asp Lys Val Gln Leu Ala Met Gln Thr Tyr Glu Met Val Asp Lys His 85 90 95 Ile Arg Arg Leu Asp Thr Asp Leu Ala Arg Phe Glu Ala Asp Leu Lys 100 105 110 Glu Lys Gln Ile Glu Ser Ser Asp Tyr Asp Ser Ser Ser Ser Lys Gly 115 120 125 Lys Lys Lys Gly Arg Thr Gln Lys Glu Lys Lys Ala Ala Arg Ala Arg 130 135 140 Ser Lys Gly Lys Asn Ser Asp Glu Glu Ala Pro Lys Thr Ala Gln Lys 145 150 155 160 Lys Leu Lys Leu Val Arg Thr Val Pro Leu Ser Gly Ser Ile Leu Pro 165 170 175 Val Trp Gly <210> SEQ ID NO 23 <211> LENGTH: 249 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 23 Met Ala Ala Gly Met Tyr Leu Glu His Tyr Leu Asp Ser Ile Glu Asn 1 5 10 15 Leu Pro Phe Glu Leu Gln Arg Asn Phe Gln Leu Met Arg Asp Leu Asp 20 25 30 Gln Arg Thr Glu Asp Leu Lys Ala Glu Ile Asp Lys Leu Ala Thr Glu 35 40 45 Tyr Met Ser Ser Ala Arg Ser Leu Ser Ser Glu Glu Lys Leu Ala Leu 50 55 60 Leu Lys Gln Ile Gln Glu Ala Tyr Gly Lys Cys Lys Glu Phe Gly Asp 65 70 75 80 Asp Lys Val Gln Leu Ala Met Gln Thr Tyr Glu Met Val Asp Lys His 85 90 95 Ile Arg Arg Leu Asp Thr Asp Leu Ala Arg Phe Glu Ala Asp Leu Lys 100 105 110 Glu Lys Gln Ile Glu Ser Ser Asp Tyr Asp Ser Ser Ser Ser Lys Gly 115 120 125 Lys Lys Lys Gly Arg Thr Gln Lys Glu Lys Lys Ala Ala Arg Ala Arg 130 135 140 Ser Lys Gly Lys Asn Ser Asp Glu Glu Ala Pro Lys Thr Ala Gln Lys 145 150 155 160 Lys Leu Lys Leu Val Arg Thr Ser Pro Glu Tyr Gly Met Pro Ser Val 165 170 175

Thr Phe Gly Ser Val His Pro Ser Asp Val Leu Asp Met Pro Val Asp 180 185 190 Pro Asn Glu Pro Thr Tyr Cys Leu Cys His Gln Val Ser Tyr Gly Glu 195 200 205 Met Ile Gly Cys Asp Asn Pro Asp Cys Ser Ile Glu Trp Phe His Phe 210 215 220 Ala Cys Val Gly Leu Thr Thr Lys Pro Arg Gly Lys Trp Phe Cys Pro 225 230 235 240 Arg Cys Ser Gln Glu Arg Lys Lys Lys 245 <210> SEQ ID NO 24 <211> LENGTH: 142 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 24 Met Gly Ala Pro Thr Leu Pro Pro Ala Trp Gln Pro Phe Leu Lys Asp 1 5 10 15 His Arg Ile Ser Thr Phe Lys Asn Trp Pro Phe Leu Glu Gly Cys Ala 20 25 30 Cys Thr Pro Glu Arg Met Ala Glu Ala Gly Phe Ile His Cys Pro Thr 35 40 45 Glu Asn Glu Pro Asp Leu Ala Gln Cys Phe Phe Cys Phe Lys Glu Leu 50 55 60 Glu Gly Trp Glu Pro Asp Asp Asp Pro Ile Glu Glu His Lys Lys His 65 70 75 80 Ser Ser Gly Cys Ala Phe Leu Ser Val Lys Lys Gln Phe Glu Glu Leu 85 90 95 Thr Leu Gly Glu Phe Leu Lys Leu Asp Arg Glu Arg Ala Lys Asn Lys 100 105 110 Ile Ala Lys Glu Thr Asn Asn Lys Lys Lys Glu Phe Glu Glu Thr Ala 115 120 125 Glu Lys Val Arg Arg Ala Ile Glu Gln Leu Ala Ala Met Asp 130 135 140 <210> SEQ ID NO 25 <211> LENGTH: 137 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 25 Met Gly Ala Pro Thr Leu Pro Pro Ala Trp Gln Pro Phe Leu Lys Asp 1 5 10 15 His Arg Ile Ser Thr Phe Lys Asn Trp Pro Phe Leu Glu Gly Cys Ala 20 25 30 Cys Thr Pro Glu Arg Met Ala Glu Ala Gly Phe Ile His Cys Pro Thr 35 40 45 Glu Asn Glu Pro Asp Leu Ala Gln Cys Phe Phe Cys Phe Lys Glu Leu 50 55 60 Glu Gly Trp Glu Pro Asp Asp Asp Pro Met Gln Arg Lys Pro Thr Ile 65 70 75 80 Arg Arg Lys Asn Leu Arg Lys Leu Arg Arg Lys Cys Ala Val Pro Ser 85 90 95 Ser Ser Trp Leu Pro Trp Ile Glu Ala Ser Gly Arg Ser Cys Leu Val 100 105 110 Pro Glu Trp Leu His His Phe Gln Gly Leu Phe Pro Gly Ala Thr Ser 115 120 125 Leu Pro Val Gly Pro Leu Ala Met Ser 130 135 <210> SEQ ID NO 26 <211> LENGTH: 165 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 26 Met Gly Ala Pro Thr Leu Pro Pro Ala Trp Gln Pro Phe Leu Lys Asp 1 5 10 15 His Arg Ile Ser Thr Phe Lys Asn Trp Pro Phe Leu Glu Gly Cys Ala 20 25 30 Cys Thr Pro Glu Arg Met Ala Glu Ala Gly Phe Ile His Cys Pro Thr 35 40 45 Glu Asn Glu Pro Asp Leu Ala Gln Cys Phe Phe Cys Phe Lys Glu Leu 50 55 60 Glu Gly Trp Glu Pro Asp Asp Asp Pro Ile Gly Pro Gly Thr Val Ala 65 70 75 80 Tyr Ala Cys Asn Thr Ser Thr Leu Gly Gly Arg Gly Gly Arg Ile Thr 85 90 95 Arg Glu Glu His Lys Lys His Ser Ser Gly Cys Ala Phe Leu Ser Val 100 105 110 Lys Lys Gln Phe Glu Glu Leu Thr Leu Gly Glu Phe Leu Lys Leu Asp 115 120 125 Arg Glu Arg Ala Lys Asn Lys Ile Ala Lys Glu Thr Asn Asn Lys Lys 130 135 140 Lys Glu Phe Glu Glu Thr Ala Glu Lys Val Arg Arg Ala Ile Glu Gln 145 150 155 160 Leu Ala Ala Met Asp 165 <210> SEQ ID NO 27 <211> LENGTH: 497 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 27 Met Thr Phe Asn Ser Phe Glu Gly Ser Lys Thr Cys Val Pro Ala Asp 1 5 10 15 Ile Asn Lys Glu Glu Glu Phe Val Glu Glu Phe Asn Arg Leu Lys Thr 20 25 30 Phe Ala Asn Phe Pro Ser Gly Ser Pro Val Ser Ala Ser Thr Leu Ala 35 40 45 Arg Ala Gly Phe Leu Tyr Thr Gly Glu Gly Asp Thr Val Arg Cys Phe 50 55 60 Ser Cys His Ala Ala Val Asp Arg Trp Gln Tyr Gly Asp Ser Ala Val 65 70 75 80 Gly Arg His Arg Lys Val Ser Pro Asn Cys Arg Phe Ile Asn Gly Phe 85 90 95 Tyr Leu Glu Asn Ser Ala Thr Gln Ser Thr Asn Ser Gly Ile Gln Asn 100 105 110 Gly Gln Tyr Lys Val Glu Asn Tyr Leu Gly Ser Arg Asp His Phe Ala 115 120 125 Leu Asp Arg Pro Ser Glu Thr His Ala Asp Tyr Leu Leu Arg Thr Gly 130 135 140 Gln Val Val Asp Ile Ser Asp Thr Ile Tyr Pro Arg Asn Pro Ala Met 145 150 155 160 Tyr Ser Glu Glu Ala Arg Leu Lys Ser Phe Gln Asn Trp Pro Asp Tyr 165 170 175 Ala His Leu Thr Pro Arg Glu Leu Ala Ser Ala Gly Leu Tyr Tyr Thr 180 185 190 Gly Ile Gly Asp Gln Val Gln Cys Phe Cys Cys Gly Gly Lys Leu Lys 195 200 205 Asn Trp Glu Pro Cys Asp Arg Ala Trp Ser Glu His Arg Arg His Phe 210 215 220 Pro Asn Cys Phe Phe Val Leu Gly Arg Asn Leu Asn Ile Arg Ser Glu 225 230 235 240 Ser Asp Ala Val Ser Ser Asp Arg Asn Phe Pro Asn Ser Thr Asn Leu 245 250 255 Pro Arg Asn Pro Ser Met Ala Asp Tyr Glu Ala Arg Ile Phe Thr Phe 260 265 270 Gly Thr Trp Ile Tyr Ser Val Asn Lys Glu Gln Leu Ala Arg Ala Gly 275 280 285 Phe Tyr Ala Leu Gly Glu Gly Asp Lys Val Lys Cys Phe His Cys Gly 290 295 300 Gly Gly Leu Thr Asp Trp Lys Pro Ser Glu Asp Pro Trp Glu Gln His 305 310 315 320 Ala Lys Trp Tyr Pro Gly Cys Lys Tyr Leu Leu Glu Gln Lys Gly Gln 325 330 335 Glu Tyr Ile Asn Asn Ile His Leu Thr His Ser Leu Glu Glu Cys Leu 340 345 350 Val Arg Thr Thr Glu Lys Thr Pro Ser Leu Thr Arg Arg Ile Asp Asp 355 360 365 Thr Ile Phe Gln Asn Pro Met Val Gln Glu Ala Ile Arg Met Gly Phe 370 375 380 Ser Phe Lys Asp Ile Lys Lys Ile Met Glu Glu Lys Ile Gln Ile Ser 385 390 395 400 Gly Ser Asn Tyr Lys Ser Leu Glu Val Leu Val Ala Asp Leu Val Asn 405 410 415 Ala Gln Lys Asp Ser Met Gln Asp Glu Ser Ser Gln Thr Ser Leu Gln 420 425 430 Lys Glu Ile Ser Thr Glu Glu Gln Leu Arg Arg Leu Gln Glu Glu Lys 435 440 445 Leu Cys Lys Ile Cys Met Asp Arg Asn Ile Ala Ile Val Phe Val Pro 450 455 460 Cys Gly His Leu Val Thr Cys Lys Gln Cys Ala Glu Ala Val Asp Lys 465 470 475 480 Cys Pro Met Cys Tyr Thr Val Ile Thr Phe Lys Gln Lys Ile Phe Met 485 490 495 Ser <210> SEQ ID NO 28 <211> LENGTH: 1403 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 28 Met Ala Thr Gln Gln Lys Ala Ser Asp Glu Arg Ile Ser Gln Phe Asp 1 5 10 15 His Asn Leu Leu Pro Glu Leu Ser Ala Leu Leu Gly Leu Asp Ala Val 20 25 30 Gln Leu Ala Lys Glu Leu Glu Glu Glu Glu Gln Lys Glu Arg Ala Lys 35 40 45 Met Gln Lys Gly Tyr Asn Ser Gln Met Arg Ser Glu Ala Lys Arg Leu 50 55 60 Lys Thr Phe Val Thr Tyr Glu Pro Tyr Ser Ser Trp Ile Pro Gln Glu 65 70 75 80

Met Ala Ala Ala Gly Phe Tyr Phe Thr Gly Val Lys Ser Gly Ile Gln 85 90 95 Cys Phe Cys Cys Ser Leu Ile Leu Phe Gly Ala Gly Leu Thr Arg Leu 100 105 110 Pro Ile Glu Asp His Lys Arg Phe His Pro Asp Cys Gly Phe Leu Leu 115 120 125 Asn Lys Asp Val Gly Asn Ile Ala Lys Tyr Asp Ile Arg Val Lys Asn 130 135 140 Leu Lys Ser Arg Leu Arg Gly Gly Lys Met Arg Tyr Gln Glu Glu Glu 145 150 155 160 Ala Arg Leu Ala Ser Phe Arg Asn Trp Pro Phe Tyr Val Gln Gly Ile 165 170 175 Ser Pro Cys Val Leu Ser Glu Ala Gly Phe Val Phe Thr Gly Lys Gln 180 185 190 Asp Thr Val Gln Cys Phe Ser Cys Gly Gly Cys Leu Gly Asn Trp Glu 195 200 205 Glu Gly Asp Asp Pro Trp Lys Glu His Ala Lys Trp Phe Pro Lys Cys 210 215 220 Glu Phe Leu Arg Ser Lys Lys Ser Ser Glu Glu Ile Thr Gln Tyr Ile 225 230 235 240 Gln Ser Tyr Lys Gly Phe Val Asp Ile Thr Gly Glu His Phe Val Asn 245 250 255 Ser Trp Val Gln Arg Glu Leu Pro Met Ala Ser Ala Tyr Cys Asn Asp 260 265 270 Ser Ile Phe Ala Tyr Glu Glu Leu Arg Leu Asp Ser Phe Lys Asp Trp 275 280 285 Pro Arg Glu Ser Ala Val Gly Val Ala Ala Leu Ala Lys Ala Gly Leu 290 295 300 Phe Tyr Thr Gly Ile Lys Asp Ile Val Gln Cys Phe Ser Cys Gly Gly 305 310 315 320 Cys Leu Glu Lys Trp Gln Glu Gly Asp Asp Pro Leu Asp Asp His Thr 325 330 335 Arg Cys Phe Pro Asn Cys Pro Phe Leu Gln Asn Met Lys Ser Ser Ala 340 345 350 Glu Val Thr Pro Asp Leu Gln Ser Arg Gly Glu Leu Cys Glu Leu Leu 355 360 365 Glu Thr Thr Ser Glu Ser Asn Leu Glu Asp Ser Ile Ala Val Gly Pro 370 375 380 Ile Val Pro Glu Met Ala Gln Gly Glu Ala Gln Trp Phe Gln Glu Ala 385 390 395 400 Lys Asn Leu Asn Glu Gln Leu Arg Ala Ala Tyr Thr Ser Ala Ser Phe 405 410 415 Arg His Met Ser Leu Leu Asp Ile Ser Ser Asp Leu Ala Thr Asp His 420 425 430 Leu Leu Gly Cys Asp Leu Ser Ile Ala Ser Lys His Ile Ser Lys Pro 435 440 445 Val Gln Glu Pro Leu Val Leu Pro Glu Val Phe Gly Asn Leu Asn Ser 450 455 460 Val Met Cys Val Glu Gly Glu Ala Gly Ser Gly Lys Thr Val Leu Leu 465 470 475 480 Lys Lys Ile Ala Phe Leu Trp Ala Ser Gly Cys Cys Pro Leu Leu Asn 485 490 495 Arg Phe Gln Leu Val Phe Tyr Leu Ser Leu Ser Ser Thr Arg Pro Asp 500 505 510 Glu Gly Leu Ala Ser Ile Ile Cys Asp Gln Leu Leu Glu Lys Glu Gly 515 520 525 Ser Val Thr Glu Met Cys Val Arg Asn Ile Ile Gln Gln Leu Lys Asn 530 535 540 Gln Val Leu Phe Leu Leu Asp Asp Tyr Lys Glu Ile Cys Ser Ile Pro 545 550 555 560 Gln Val Ile Gly Lys Leu Ile Gln Lys Asn His Leu Ser Arg Thr Cys 565 570 575 Leu Leu Ile Ala Val Arg Thr Asn Arg Ala Arg Asp Ile Arg Arg Tyr 580 585 590 Leu Glu Thr Ile Leu Glu Ile Lys Ala Phe Pro Phe Tyr Asn Thr Val 595 600 605 Cys Ile Leu Arg Lys Leu Phe Ser His Asn Met Thr Arg Leu Arg Lys 610 615 620 Phe Met Val Tyr Phe Gly Lys Asn Gln Ser Leu Gln Lys Ile Gln Lys 625 630 635 640 Thr Pro Leu Phe Val Ala Ala Ile Cys Ala His Trp Phe Gln Tyr Pro 645 650 655 Phe Asp Pro Ser Phe Asp Asp Val Ala Val Phe Lys Ser Tyr Met Glu 660 665 670 Arg Leu Ser Leu Arg Asn Lys Ala Thr Ala Glu Ile Leu Lys Ala Thr 675 680 685 Val Ser Ser Cys Gly Glu Leu Ala Leu Lys Gly Phe Phe Ser Cys Cys 690 695 700 Phe Glu Phe Asn Asp Asp Asp Leu Ala Glu Ala Gly Val Asp Glu Asp 705 710 715 720 Glu Asp Leu Thr Met Cys Leu Met Ser Lys Phe Thr Ala Gln Arg Leu 725 730 735 Arg Pro Phe Tyr Arg Phe Leu Ser Pro Ala Phe Gln Glu Phe Leu Ala 740 745 750 Gly Met Arg Leu Ile Glu Leu Leu Asp Ser Asp Arg Gln Glu His Gln 755 760 765 Asp Leu Gly Leu Tyr His Leu Lys Gln Ile Asn Ser Pro Met Met Thr 770 775 780 Val Ser Ala Tyr Asn Asn Phe Leu Asn Tyr Val Ser Ser Leu Pro Ser 785 790 795 800 Thr Lys Ala Gly Pro Lys Ile Val Ser His Leu Leu His Leu Val Asp 805 810 815 Asn Lys Glu Ser Leu Glu Asn Ile Ser Glu Asn Asp Asp Tyr Leu Lys 820 825 830 His Gln Pro Glu Ile Ser Leu Gln Met Gln Leu Leu Arg Gly Leu Trp 835 840 845 Gln Ile Cys Pro Gln Ala Tyr Phe Ser Met Val Ser Glu His Leu Leu 850 855 860 Val Leu Ala Leu Lys Thr Ala Tyr Gln Ser Asn Thr Val Ala Ala Cys 865 870 875 880 Ser Pro Phe Val Leu Gln Phe Leu Gln Gly Arg Thr Leu Thr Leu Gly 885 890 895 Ala Leu Asn Leu Gln Tyr Phe Phe Asp His Pro Glu Ser Leu Ser Leu 900 905 910 Leu Arg Ser Ile His Phe Pro Ile Arg Gly Asn Lys Thr Ser Pro Arg 915 920 925 Ala His Phe Ser Val Leu Glu Thr Cys Phe Asp Lys Ser Gln Val Pro 930 935 940 Thr Ile Asp Gln Asp Tyr Ala Ser Ala Phe Glu Pro Met Asn Glu Trp 945 950 955 960 Glu Arg Asn Leu Ala Glu Lys Glu Asp Asn Val Lys Ser Tyr Met Asp 965 970 975 Met Gln Arg Arg Ala Ser Pro Asp Leu Ser Thr Gly Tyr Trp Lys Leu 980 985 990 Ser Pro Lys Gln Tyr Lys Ile Pro Cys Leu Glu Val Asp Val Asn Asp 995 1000 1005 Ile Asp Val Val Gly Gln Asp Met Leu Glu Ile Leu Met Thr Val Phe 1010 1015 1020 Ser Ala Ser Gln Arg Ile Glu Leu His Leu Asn His Ser Arg Gly Phe 1025 1030 1035 1040 Ile Glu Ser Ile Arg Pro Ala Leu Glu Leu Ser Lys Ala Ser Val Thr 1045 1050 1055 Lys Cys Ser Ile Ser Lys Leu Glu Leu Ser Ala Ala Glu Gln Glu Leu 1060 1065 1070 Leu Leu Thr Leu Pro Ser Leu Glu Ser Leu Glu Val Ser Gly Thr Ile 1075 1080 1085 Gln Ser Gln Asp Gln Ile Phe Pro Asn Leu Asp Lys Phe Leu Cys Leu 1090 1095 1100 Lys Glu Leu Ser Val Asp Leu Glu Gly Asn Ile Asn Val Phe Ser Val 1105 1110 1115 1120 Ile Pro Glu Glu Phe Pro Asn Phe His His Met Glu Lys Leu Leu Ile 1125 1130 1135 Gln Ile Ser Ala Glu Tyr Asp Pro Ser Lys Leu Val Lys Leu Ile Gln 1140 1145 1150 Asn Ser Pro Asn Leu His Val Phe His Leu Lys Cys Asn Phe Phe Ser 1155 1160 1165 Asp Phe Gly Ser Leu Met Thr Met Leu Val Ser Cys Lys Lys Leu Thr 1170 1175 1180 Glu Ile Lys Phe Ser Asp Ser Phe Phe Gln Ala Val Pro Phe Val Ala 1185 1190 1195 1200 Ser Leu Pro Asn Phe Ile Ser Leu Lys Ile Leu Asn Leu Glu Gly Gln 1205 1210 1215 Gln Phe Pro Asp Glu Glu Thr Ser Glu Lys Phe Ala Tyr Ile Leu Gly 1220 1225 1230 Ser Leu Ser Asn Leu Glu Glu Leu Ile Leu Pro Thr Gly Asp Gly Ile 1235 1240 1245 Tyr Arg Val Ala Lys Leu Ile Ile Gln Gln Cys Gln Gln Leu His Cys 1250 1255 1260 Leu Arg Val Leu Ser Phe Phe Lys Thr Leu Asn Asp Asp Ser Val Val 1265 1270 1275 1280 Glu Ile Ala Lys Val Ala Ile Ser Gly Gly Phe Gln Lys Leu Glu Asn 1285 1290 1295 Leu Lys Leu Ser Ile Asn His Lys Ile Thr Glu Glu Gly Tyr Arg Asn 1300 1305 1310 Phe Phe Gln Ala Leu Asp Asn Met Pro Asn Leu Gln Glu Leu Asp Ile 1315 1320 1325 Ser Arg His Phe Thr Glu Cys Ile Lys Ala Gln Ala Thr Thr Val Lys 1330 1335 1340 Ser Leu Ser Gln Cys Val Leu Arg Leu Pro Arg Leu Ile Arg Leu Asn 1345 1350 1355 1360 Met Leu Ser Trp Leu Leu Asp Ala Asp Asp Ile Ala Leu Leu Asn Val 1365 1370 1375 Met Lys Glu Arg His Pro Gln Ser Lys Tyr Leu Thr Ile Leu Gln Lys 1380 1385 1390 Trp Ile Leu Pro Phe Ser Pro Ile Ile Gln Lys 1395 1400 <210> SEQ ID NO 29

<211> LENGTH: 1241 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 29 Met Pro Leu His Ile Gly Asp Phe Val Trp Asp Ser Lys Val His Ser 1 5 10 15 Leu Gln Ser Ser Leu Asn Ile Phe Ser Leu Leu Pro Thr Lys Gly Arg 20 25 30 Thr Glu His Leu Phe Phe Ser His Ile Leu Ser Phe His Trp Pro Ala 35 40 45 Phe Ser Ser Ile Arg Leu Glu Leu Trp Ile Asn Leu Arg Cys Glu Phe 50 55 60 Leu Arg Ser Lys Lys Ser Ser Glu Glu Ile Thr Gln Tyr Ile Gln Ser 65 70 75 80 Tyr Lys Gly Phe Val Asp Ile Thr Gly Glu His Phe Val Asn Ser Trp 85 90 95 Val Gln Arg Glu Leu Pro Met Ala Ser Ala Tyr Cys Asn Asp Ser Ile 100 105 110 Phe Ala Tyr Glu Glu Leu Arg Leu Asp Ser Phe Lys Asp Trp Pro Arg 115 120 125 Glu Ser Ala Val Gly Val Ala Ala Leu Ala Lys Ala Gly Leu Phe Tyr 130 135 140 Thr Gly Ile Lys Asp Ile Val Gln Cys Phe Ser Cys Gly Gly Cys Leu 145 150 155 160 Glu Lys Trp Gln Glu Gly Asp Asp Pro Leu Asp Asp His Thr Arg Cys 165 170 175 Phe Pro Asn Cys Pro Phe Leu Gln Asn Met Lys Ser Ser Ala Glu Val 180 185 190 Thr Pro Asp Leu Gln Ser Arg Gly Glu Leu Cys Glu Leu Leu Glu Thr 195 200 205 Thr Ser Glu Ser Asn Leu Glu Asp Ser Ile Ala Val Gly Pro Ile Val 210 215 220 Pro Glu Met Ala Gln Gly Glu Ala Gln Trp Phe Gln Glu Ala Lys Asn 225 230 235 240 Leu Asn Glu Gln Leu Arg Ala Ala Tyr Thr Ser Ala Ser Phe Arg His 245 250 255 Met Ser Leu Leu Asp Ile Ser Ser Asp Leu Ala Thr Asp His Leu Leu 260 265 270 Gly Cys Asp Leu Ser Ile Ala Ser Lys His Ile Ser Lys Pro Val Gln 275 280 285 Glu Pro Leu Val Leu Pro Glu Val Phe Gly Asn Leu Asn Ser Val Met 290 295 300 Cys Val Glu Gly Glu Ala Gly Ser Gly Lys Thr Val Leu Leu Lys Lys 305 310 315 320 Ile Ala Phe Leu Trp Ala Ser Gly Cys Cys Pro Leu Leu Asn Arg Phe 325 330 335 Gln Leu Val Phe Tyr Leu Ser Leu Ser Ser Thr Arg Pro Asp Glu Gly 340 345 350 Leu Ala Ser Ile Ile Cys Asp Gln Leu Leu Glu Lys Glu Gly Ser Val 355 360 365 Thr Glu Met Cys Val Arg Asn Ile Ile Gln Gln Leu Lys Asn Gln Val 370 375 380 Leu Phe Leu Leu Asp Asp Tyr Lys Glu Ile Cys Ser Ile Pro Gln Val 385 390 395 400 Ile Gly Lys Leu Ile Gln Lys Asn His Leu Ser Arg Thr Cys Leu Leu 405 410 415 Ile Ala Val Arg Thr Asn Arg Ala Arg Asp Ile Arg Arg Tyr Leu Glu 420 425 430 Thr Ile Leu Glu Ile Lys Ala Phe Pro Phe Tyr Asn Thr Val Cys Ile 435 440 445 Leu Arg Lys Leu Phe Ser His Asn Met Thr Arg Leu Arg Lys Phe Met 450 455 460 Val Tyr Phe Gly Lys Asn Gln Ser Leu Gln Lys Ile Gln Lys Thr Pro 465 470 475 480 Leu Phe Val Ala Ala Ile Cys Ala His Trp Phe Gln Tyr Pro Phe Asp 485 490 495 Pro Ser Phe Asp Asp Val Ala Val Phe Lys Ser Tyr Met Glu Arg Leu 500 505 510 Ser Leu Arg Asn Lys Ala Thr Ala Glu Ile Leu Lys Ala Thr Val Ser 515 520 525 Ser Cys Gly Glu Leu Ala Leu Lys Gly Phe Phe Ser Cys Cys Phe Glu 530 535 540 Phe Asn Asp Asp Asp Leu Ala Glu Ala Gly Val Asp Glu Asp Glu Asp 545 550 555 560 Leu Thr Met Cys Leu Met Ser Lys Phe Thr Ala Gln Arg Leu Arg Pro 565 570 575 Phe Tyr Arg Phe Leu Ser Pro Ala Phe Gln Glu Phe Leu Ala Gly Met 580 585 590 Arg Leu Ile Glu Leu Leu Asp Ser Asp Arg Gln Glu His Gln Asp Leu 595 600 605 Gly Leu Tyr His Leu Lys Gln Ile Asn Ser Pro Met Met Thr Val Ser 610 615 620 Ala Tyr Asn Asn Phe Leu Asn Tyr Val Ser Ser Leu Pro Ser Thr Lys 625 630 635 640 Ala Gly Pro Lys Ile Val Ser His Leu Leu His Leu Val Asp Asn Lys 645 650 655 Glu Ser Leu Glu Asn Ile Ser Glu Asn Asp Asp Tyr Leu Lys His Gln 660 665 670 Pro Glu Ile Ser Leu Gln Met Gln Leu Leu Arg Gly Leu Trp Gln Ile 675 680 685 Cys Pro Gln Ala Tyr Phe Ser Met Val Ser Glu His Leu Leu Val Leu 690 695 700 Ala Leu Lys Thr Ala Tyr Gln Ser Asn Thr Val Ala Ala Cys Ser Pro 705 710 715 720 Phe Val Leu Gln Phe Leu Gln Gly Arg Thr Leu Thr Leu Gly Ala Leu 725 730 735 Asn Leu Gln Tyr Phe Phe Asp His Pro Glu Ser Leu Ser Leu Leu Arg 740 745 750 Ser Ile His Phe Pro Ile Arg Gly Asn Lys Thr Ser Pro Arg Ala His 755 760 765 Phe Ser Val Leu Glu Thr Cys Phe Asp Lys Ser Gln Val Pro Thr Ile 770 775 780 Asp Gln Asp Tyr Ala Ser Ala Phe Glu Pro Met Asn Glu Trp Glu Arg 785 790 795 800 Asn Leu Ala Glu Lys Glu Asp Asn Val Lys Ser Tyr Met Asp Met Gln 805 810 815 Arg Arg Ala Ser Pro Asp Leu Ser Thr Gly Tyr Trp Lys Leu Ser Pro 820 825 830 Lys Gln Tyr Lys Ile Pro Cys Leu Glu Val Asp Val Asn Asp Ile Asp 835 840 845 Val Val Gly Gln Asp Met Leu Glu Ile Leu Met Thr Val Phe Ser Ala 850 855 860 Ser Gln Arg Ile Glu Leu His Leu Asn His Ser Arg Gly Phe Ile Glu 865 870 875 880 Ser Ile Arg Pro Ala Leu Glu Leu Ser Lys Ala Ser Val Thr Lys Cys 885 890 895 Ser Ile Ser Lys Leu Glu Leu Ser Ala Ala Glu Gln Glu Leu Leu Leu 900 905 910 Thr Leu Pro Ser Leu Glu Ser Leu Glu Val Ser Gly Thr Ile Gln Ser 915 920 925 Gln Asp Gln Ile Phe Pro Asn Leu Asp Lys Phe Leu Cys Leu Lys Glu 930 935 940 Leu Ser Val Asp Leu Glu Gly Asn Ile Asn Val Phe Ser Val Ile Pro 945 950 955 960 Glu Glu Phe Pro Asn Phe His His Met Glu Lys Leu Leu Ile Gln Ile 965 970 975 Ser Ala Glu Tyr Asp Pro Ser Lys Leu Val Lys Leu Ile Gln Asn Ser 980 985 990 Pro Asn Leu His Val Phe His Leu Lys Cys Asn Phe Phe Ser Asp Phe 995 1000 1005 Gly Ser Leu Met Thr Met Leu Val Ser Cys Lys Lys Leu Thr Glu Ile 1010 1015 1020 Lys Phe Ser Asp Ser Phe Phe Gln Ala Val Pro Phe Val Ala Ser Leu 1025 1030 1035 1040 Pro Asn Phe Ile Ser Leu Lys Ile Leu Asn Leu Glu Gly Gln Gln Phe 1045 1050 1055 Pro Asp Glu Glu Thr Ser Glu Lys Phe Ala Tyr Ile Leu Gly Ser Leu 1060 1065 1070 Ser Asn Leu Glu Glu Leu Ile Leu Pro Thr Gly Asp Gly Ile Tyr Arg 1075 1080 1085 Val Ala Lys Leu Ile Ile Gln Gln Cys Gln Gln Leu His Cys Leu Arg 1090 1095 1100 Val Leu Ser Phe Phe Lys Thr Leu Asn Asp Asp Ser Val Val Glu Ile 1105 1110 1115 1120 Ala Lys Val Ala Ile Ser Gly Gly Phe Gln Lys Leu Glu Asn Leu Lys 1125 1130 1135 Leu Ser Ile Asn His Lys Ile Thr Glu Glu Gly Tyr Arg Asn Phe Phe 1140 1145 1150 Gln Ala Leu Asp Asn Met Pro Asn Leu Gln Glu Leu Asp Ile Ser Arg 1155 1160 1165 His Phe Thr Glu Cys Ile Lys Ala Gln Ala Thr Thr Val Lys Ser Leu 1170 1175 1180 Ser Gln Cys Val Leu Arg Leu Pro Arg Leu Ile Arg Leu Asn Met Leu 1185 1190 1195 1200 Ser Trp Leu Leu Asp Ala Asp Asp Ile Ala Leu Leu Asn Val Met Lys 1205 1210 1215 Glu Arg His Pro Gln Ser Lys Tyr Leu Thr Ile Leu Gln Lys Trp Ile 1220 1225 1230 Leu Pro Phe Ser Pro Ile Ile Gln Lys 1235 1240 <210> SEQ ID NO 30 <211> LENGTH: 233 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 30 Met Ser Thr Glu Ser Met Ile Arg Asp Val Glu Leu Ala Glu Glu Ala 1 5 10 15

Leu Pro Lys Lys Thr Gly Gly Pro Gln Gly Ser Arg Arg Cys Leu Phe 20 25 30 Leu Ser Leu Phe Ser Phe Leu Ile Val Ala Gly Ala Thr Thr Leu Phe 35 40 45 Cys Leu Leu His Phe Gly Val Ile Gly Pro Gln Arg Glu Glu Phe Pro 50 55 60 Arg Asp Leu Ser Leu Ile Ser Pro Leu Ala Gln Ala Val Arg Ser Ser 65 70 75 80 Ser Arg Thr Pro Ser Asp Lys Pro Val Ala His Val Val Ala Asn Pro 85 90 95 Gln Ala Glu Gly Gln Leu Gln Trp Leu Asn Arg Arg Ala Asn Ala Leu 100 105 110 Leu Ala Asn Gly Val Glu Leu Arg Asp Asn Gln Leu Val Val Pro Ser 115 120 125 Glu Gly Leu Tyr Leu Ile Tyr Ser Gln Val Leu Phe Lys Gly Gln Gly 130 135 140 Cys Pro Ser Thr His Val Leu Leu Thr His Thr Ile Ser Arg Ile Ala 145 150 155 160 Val Ser Tyr Gln Thr Lys Val Asn Leu Leu Ser Ala Ile Lys Ser Pro 165 170 175 Cys Gln Arg Glu Thr Pro Glu Gly Ala Glu Ala Lys Pro Trp Tyr Glu 180 185 190 Pro Ile Tyr Leu Gly Gly Val Phe Gln Leu Glu Lys Gly Asp Arg Leu 195 200 205 Ser Ala Glu Ile Asn Arg Pro Asp Tyr Leu Asp Phe Ala Glu Ser Gly 210 215 220 Gln Val Tyr Phe Gly Ile Ile Ala Leu 225 230 <210> SEQ ID NO 31 <211> LENGTH: 189 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 31 Met Ala Ser Pro Phe Ala Leu Leu Met Val Leu Val Val Leu Ser Cys 1 5 10 15 Lys Ser Ser Cys Ser Leu Gly Cys Asp Leu Pro Glu Thr His Ser Leu 20 25 30 Asp Asn Arg Arg Thr Leu Met Leu Leu Ala Gln Met Ser Arg Ile Ser 35 40 45 Pro Ser Ser Cys Leu Met Asp Arg His Asp Phe Gly Phe Pro Gln Glu 50 55 60 Glu Phe Asp Gly Asn Gln Phe Gln Lys Ala Pro Ala Ile Ser Val Leu 65 70 75 80 His Glu Leu Ile Gln Gln Ile Phe Asn Leu Phe Thr Thr Lys Asp Ser 85 90 95 Ser Ala Ala Trp Asp Glu Asp Leu Leu Asp Lys Phe Cys Thr Glu Leu 100 105 110 Tyr Gln Gln Leu Asn Asp Leu Glu Ala Cys Val Met Gln Glu Glu Arg 115 120 125 Val Gly Glu Thr Pro Leu Met Asn Ala Asp Ser Ile Leu Ala Val Lys 130 135 140 Lys Tyr Phe Arg Arg Ile Thr Leu Tyr Leu Thr Glu Lys Lys Tyr Ser 145 150 155 160 Pro Cys Ala Trp Glu Val Val Arg Ala Glu Ile Met Arg Ser Leu Ser 165 170 175 Leu Ser Thr Asn Leu Gln Glu Arg Leu Arg Arg Lys Glu 180 185 <210> SEQ ID NO 32 <211> LENGTH: 187 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 32 Met Thr Asn Lys Cys Leu Leu Gln Ile Ala Leu Leu Leu Cys Phe Ser 1 5 10 15 Thr Thr Ala Leu Ser Met Ser Tyr Asn Leu Leu Gly Phe Leu Gln Arg 20 25 30 Ser Ser Asn Phe Gln Cys Gln Lys Leu Leu Trp Gln Leu Asn Gly Arg 35 40 45 Leu Glu Tyr Cys Leu Lys Asp Arg Met Asn Phe Asp Ile Pro Glu Glu 50 55 60 Ile Lys Gln Leu Gln Gln Phe Gln Lys Glu Asp Ala Ala Leu Thr Ile 65 70 75 80 Tyr Glu Met Leu Gln Asn Ile Phe Ala Ile Phe Arg Gln Asp Ser Ser 85 90 95 Ser Thr Gly Trp Asn Glu Thr Ile Val Glu Asn Leu Leu Ala Asn Val 100 105 110 Tyr His Gln Ile Asn His Leu Lys Thr Val Leu Glu Glu Lys Leu Glu 115 120 125 Lys Glu Asp Phe Thr Arg Gly Lys Leu Met Ser Ser Leu His Leu Lys 130 135 140 Arg Tyr Tyr Gly Arg Ile Leu His Tyr Leu Lys Ala Lys Glu Tyr Ser 145 150 155 160 His Cys Ala Trp Thr Ile Val Arg Val Glu Ile Leu Arg Asn Phe Tyr 165 170 175 Phe Ile Asn Arg Leu Thr Gly Tyr Leu Arg Asn 180 185 <210> SEQ ID NO 33 <211> LENGTH: 166 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 33 Met Lys Tyr Thr Ser Tyr Ile Leu Ala Phe Gln Leu Cys Ile Val Leu 1 5 10 15 Gly Ser Leu Gly Cys Tyr Cys Gln Asp Pro Tyr Val Lys Glu Ala Glu 20 25 30 Asn Leu Lys Lys Tyr Phe Asn Ala Gly His Ser Asp Val Ala Asp Asn 35 40 45 Gly Thr Leu Phe Leu Gly Ile Leu Lys Asn Trp Lys Glu Glu Ser Asp 50 55 60 Arg Lys Ile Met Gln Ser Gln Ile Val Ser Phe Tyr Phe Lys Leu Phe 65 70 75 80 Lys Asn Phe Lys Asp Asp Gln Ser Ile Gln Lys Ser Val Glu Thr Ile 85 90 95 Lys Glu Asp Met Asn Val Lys Phe Phe Asn Ser Asn Lys Lys Lys Arg 100 105 110 Asp Asp Phe Glu Lys Leu Thr Asn Tyr Ser Val Thr Asp Leu Asn Val 115 120 125 Gln Arg Lys Ala Ile His Glu Leu Ile Gln Val Met Ala Glu Leu Ser 130 135 140 Pro Ala Ala Lys Thr Gly Lys Arg Lys Arg Ser Gln Met Leu Phe Arg 145 150 155 160 Gly Arg Arg Ala Ser Gln 165 <210> SEQ ID NO 34 <211> LENGTH: 554 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 34 Met Thr Ala Pro Gly Ala Ala Gly Arg Cys Pro Pro Thr Thr Trp Leu 1 5 10 15 Gly Ser Leu Leu Leu Leu Val Cys Leu Leu Ala Ser Arg Ser Ile Thr 20 25 30 Glu Glu Val Ser Glu Tyr Cys Ser His Met Ile Gly Ser Gly His Leu 35 40 45 Gln Ser Leu Gln Arg Leu Ile Asp Ser Gln Met Glu Thr Ser Cys Gln 50 55 60 Ile Thr Phe Glu Phe Val Asp Gln Glu Gln Leu Lys Asp Pro Val Cys 65 70 75 80 Tyr Leu Lys Lys Ala Phe Leu Leu Val Gln Asp Ile Met Glu Asp Thr 85 90 95 Met Arg Phe Arg Asp Asn Thr Pro Asn Ala Ile Ala Ile Val Gln Leu 100 105 110 Gln Glu Leu Ser Leu Arg Leu Lys Ser Cys Phe Thr Lys Asp Tyr Glu 115 120 125 Glu His Asp Lys Ala Cys Val Arg Thr Phe Tyr Glu Thr Pro Leu Gln 130 135 140 Leu Leu Glu Lys Val Lys Asn Val Phe Asn Glu Thr Lys Asn Leu Leu 145 150 155 160 Asp Lys Asp Trp Asn Ile Phe Ser Lys Asn Cys Asn Asn Ser Phe Ala 165 170 175 Glu Cys Ser Ser Gln Asp Val Val Thr Lys Pro Asp Cys Asn Cys Leu 180 185 190 Tyr Pro Lys Ala Ile Pro Ser Ser Asp Pro Ala Ser Val Ser Pro His 195 200 205 Gln Pro Leu Ala Pro Ser Met Ala Pro Val Ala Gly Leu Thr Trp Glu 210 215 220 Asp Ser Glu Gly Thr Glu Gly Ser Ser Leu Leu Pro Gly Glu Gln Pro 225 230 235 240 Leu His Thr Val Asp Pro Gly Ser Ala Lys Gln Arg Pro Pro Arg Ser 245 250 255 Thr Cys Gln Ser Phe Glu Pro Pro Glu Thr Pro Val Val Lys Asp Ser 260 265 270 Thr Ile Gly Gly Ser Pro Gln Pro Arg Pro Ser Val Gly Ala Phe Asn 275 280 285 Pro Gly Met Glu Asp Ile Leu Asp Ser Ala Met Gly Thr Asn Trp Val 290 295 300 Pro Glu Glu Ala Ser Gly Glu Ala Ser Glu Ile Pro Val Pro Gln Gly 305 310 315 320 Thr Glu Leu Ser Pro Ser Arg Pro Gly Gly Gly Ser Met Gln Thr Glu 325 330 335 Pro Ala Arg Pro Ser Asn Phe Leu Ser Ala Ser Ser Pro Leu Pro Ala 340 345 350 Ser Ala Lys Gly Gln Gln Pro Ala Asp Val Thr Gly Thr Ala Leu Pro 355 360 365 Arg Val Gly Pro Val Arg Pro Thr Gly Gln Asp Trp Asn His Thr Pro 370 375 380

Gln Lys Thr Asp His Pro Ser Ala Leu Leu Arg Asp Pro Pro Glu Pro 385 390 395 400 Gly Ser Pro Arg Ile Ser Ser Leu Arg Pro Gln Gly Leu Ser Asn Pro 405 410 415 Ser Thr Leu Ser Ala Gln Pro Gln Leu Ser Arg Ser His Ser Ser Gly 420 425 430 Ser Val Leu Pro Leu Gly Glu Leu Glu Gly Arg Arg Ser Thr Arg Asp 435 440 445 Arg Arg Ser Pro Ala Glu Pro Glu Gly Gly Pro Ala Ser Glu Gly Ala 450 455 460 Ala Arg Pro Leu Pro Arg Phe Asn Ser Val Pro Leu Thr Asp Thr Gly 465 470 475 480 His Glu Arg Gln Ser Glu Gly Ser Ser Ser Pro Gln Leu Gln Glu Ser 485 490 495 Val Phe His Leu Leu Val Pro Ser Val Ile Leu Val Leu Leu Ala Val 500 505 510 Gly Gly Leu Leu Phe Tyr Arg Trp Arg Arg Arg Ser His Gln Glu Pro 515 520 525 Gln Arg Ala Asp Ser Pro Leu Glu Gln Pro Glu Gly Ser Pro Leu Thr 530 535 540 Gln Asp Asp Arg Gln Val Glu Leu Pro Val 545 550 <210> SEQ ID NO 35 <211> LENGTH: 554 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 35 Met Thr Ala Pro Gly Ala Ala Gly Arg Cys Pro Pro Thr Thr Trp Leu 1 5 10 15 Gly Ser Leu Leu Leu Leu Val Cys Leu Leu Ala Ser Arg Ser Ile Thr 20 25 30 Glu Glu Val Ser Glu Tyr Cys Ser His Met Ile Gly Ser Gly His Leu 35 40 45 Gln Ser Leu Gln Arg Leu Ile Asp Ser Gln Met Glu Thr Ser Cys Gln 50 55 60 Ile Thr Phe Glu Phe Val Asp Gln Glu Gln Leu Lys Asp Pro Val Cys 65 70 75 80 Tyr Leu Lys Lys Ala Phe Leu Leu Val Gln Asp Ile Met Glu Asp Thr 85 90 95 Met Arg Phe Arg Asp Asn Thr Pro Asn Ala Ile Ala Ile Val Gln Leu 100 105 110 Gln Glu Leu Ser Leu Arg Leu Lys Ser Cys Phe Thr Lys Asp Tyr Glu 115 120 125 Glu His Asp Lys Ala Cys Val Arg Thr Phe Tyr Glu Thr Pro Leu Gln 130 135 140 Leu Leu Glu Lys Val Lys Asn Val Phe Asn Glu Thr Lys Asn Leu Leu 145 150 155 160 Asp Lys Asp Trp Asn Ile Phe Ser Lys Asn Cys Asn Asn Ser Phe Ala 165 170 175 Glu Cys Ser Ser Gln Asp Val Val Thr Lys Pro Asp Cys Asn Cys Leu 180 185 190 Tyr Pro Lys Ala Ile Pro Ser Ser Asp Pro Ala Ser Val Ser Pro His 195 200 205 Gln Pro Leu Ala Pro Ser Met Ala Pro Val Ala Gly Leu Thr Trp Glu 210 215 220 Asp Ser Glu Gly Thr Glu Gly Ser Ser Leu Leu Pro Gly Glu Gln Pro 225 230 235 240 Leu His Thr Val Asp Pro Gly Ser Ala Lys Gln Arg Pro Pro Arg Ser 245 250 255 Thr Cys Gln Ser Phe Glu Pro Pro Glu Thr Pro Val Val Lys Asp Ser 260 265 270 Thr Ile Gly Gly Ser Pro Gln Pro Arg Pro Ser Val Gly Ala Phe Asn 275 280 285 Pro Gly Met Glu Asp Ile Leu Asp Ser Ala Met Gly Thr Asn Trp Val 290 295 300 Pro Glu Glu Ala Ser Gly Glu Ala Ser Glu Ile Pro Val Pro Gln Gly 305 310 315 320 Thr Glu Leu Ser Pro Ser Arg Pro Gly Gly Gly Ser Met Gln Thr Glu 325 330 335 Pro Ala Arg Pro Ser Asn Phe Leu Ser Ala Ser Ser Pro Leu Pro Ala 340 345 350 Ser Ala Lys Gly Gln Gln Pro Ala Asp Val Thr Gly Thr Ala Leu Pro 355 360 365 Arg Val Gly Pro Val Arg Pro Thr Gly Gln Asp Trp Asn His Thr Pro 370 375 380 Gln Lys Thr Asp His Pro Ser Ala Leu Leu Arg Asp Pro Pro Glu Pro 385 390 395 400 Gly Ser Pro Arg Ile Ser Ser Leu Arg Pro Gln Gly Leu Ser Asn Pro 405 410 415 Ser Thr Leu Ser Ala Gln Pro Gln Leu Ser Arg Ser His Ser Ser Gly 420 425 430 Ser Val Leu Pro Leu Gly Glu Leu Glu Gly Arg Arg Ser Thr Arg Asp 435 440 445 Arg Arg Ser Pro Ala Glu Pro Glu Gly Gly Pro Ala Ser Glu Gly Ala 450 455 460 Ala Arg Pro Leu Pro Arg Phe Asn Ser Val Pro Leu Thr Asp Thr Gly 465 470 475 480 His Glu Arg Gln Ser Glu Gly Ser Ser Ser Pro Gln Leu Gln Glu Ser 485 490 495 Val Phe His Leu Leu Val Pro Ser Val Ile Leu Val Leu Leu Ala Val 500 505 510 Gly Gly Leu Leu Phe Tyr Arg Trp Arg Arg Arg Ser His Gln Glu Pro 515 520 525 Gln Arg Ala Asp Ser Pro Leu Glu Gln Pro Glu Gly Ser Pro Leu Thr 530 535 540 Gln Asp Asp Arg Gln Val Glu Leu Pro Val 545 550 <210> SEQ ID NO 36 <211> LENGTH: 438 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 36 Met Thr Ala Pro Gly Ala Ala Gly Arg Cys Pro Pro Thr Thr Trp Leu 1 5 10 15 Gly Ser Leu Leu Leu Leu Val Cys Leu Leu Ala Ser Arg Ser Ile Thr 20 25 30 Glu Glu Val Ser Glu Tyr Cys Ser His Met Ile Gly Ser Gly His Leu 35 40 45 Gln Ser Leu Gln Arg Leu Ile Asp Ser Gln Met Glu Thr Ser Cys Gln 50 55 60 Ile Thr Phe Glu Phe Val Asp Gln Glu Gln Leu Lys Asp Pro Val Cys 65 70 75 80 Tyr Leu Lys Lys Ala Phe Leu Leu Val Gln Asp Ile Met Glu Asp Thr 85 90 95 Met Arg Phe Arg Asp Asn Thr Pro Asn Ala Ile Ala Ile Val Gln Leu 100 105 110 Gln Glu Leu Ser Leu Arg Leu Lys Ser Cys Phe Thr Lys Asp Tyr Glu 115 120 125 Glu His Asp Lys Ala Cys Val Arg Thr Phe Tyr Glu Thr Pro Leu Gln 130 135 140 Leu Leu Glu Lys Val Lys Asn Val Phe Asn Glu Thr Lys Asn Leu Leu 145 150 155 160 Asp Lys Asp Trp Asn Ile Phe Ser Lys Asn Cys Asn Asn Ser Phe Ala 165 170 175 Glu Cys Ser Ser Gln Asp Val Val Thr Lys Pro Asp Cys Asn Cys Leu 180 185 190 Tyr Pro Lys Ala Ile Pro Ser Ser Asp Pro Ala Ser Val Ser Pro His 195 200 205 Gln Pro Leu Ala Pro Ser Met Ala Pro Val Ala Gly Leu Thr Trp Glu 210 215 220 Asp Ser Glu Gly Thr Glu Gly Ser Ser Leu Leu Pro Gly Glu Gln Pro 225 230 235 240 Leu His Thr Val Asp Pro Gly Ser Ala Lys Gln Arg Pro Pro Arg Ser 245 250 255 Thr Cys Gln Ser Phe Glu Pro Pro Glu Thr Pro Val Val Lys Asp Ser 260 265 270 Thr Ile Gly Gly Ser Pro Gln Pro Arg Pro Ser Val Gly Ala Phe Asn 275 280 285 Pro Gly Met Glu Asp Ile Leu Asp Ser Ala Met Gly Thr Asn Trp Val 290 295 300 Pro Glu Glu Ala Ser Gly Glu Ala Ser Glu Ile Pro Val Pro Gln Gly 305 310 315 320 Thr Glu Leu Ser Pro Ser Arg Pro Gly Gly Gly Ser Met Gln Thr Glu 325 330 335 Pro Ala Arg Pro Ser Asn Phe Leu Ser Ala Ser Ser Pro Leu Pro Ala 340 345 350 Ser Ala Lys Gly Gln Gln Pro Ala Asp Val Thr Gly His Glu Arg Gln 355 360 365 Ser Glu Gly Ser Ser Ser Pro Gln Leu Gln Glu Ser Val Phe His Leu 370 375 380 Leu Val Pro Ser Val Ile Leu Val Leu Leu Ala Val Gly Gly Leu Leu 385 390 395 400 Phe Tyr Arg Trp Arg Arg Arg Ser His Gln Glu Pro Gln Arg Ala Asp 405 410 415 Ser Pro Leu Glu Gln Pro Glu Gly Ser Pro Leu Thr Gln Asp Asp Arg 420 425 430 Gln Val Glu Leu Pro Val 435 <210> SEQ ID NO 37 <211> LENGTH: 256 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 37 Met Thr Ala Pro Gly Ala Ala Gly Arg Cys Pro Pro Thr Thr Trp Leu 1 5 10 15 Gly Ser Leu Leu Leu Leu Val Cys Leu Leu Ala Ser Arg Ser Ile Thr 20 25 30

Glu Glu Val Ser Glu Tyr Cys Ser His Met Ile Gly Ser Gly His Leu 35 40 45 Gln Ser Leu Gln Arg Leu Ile Asp Ser Gln Met Glu Thr Ser Cys Gln 50 55 60 Ile Thr Phe Glu Phe Val Asp Gln Glu Gln Leu Lys Asp Pro Val Cys 65 70 75 80 Tyr Leu Lys Lys Ala Phe Leu Leu Val Gln Asp Ile Met Glu Asp Thr 85 90 95 Met Arg Phe Arg Asp Asn Thr Pro Asn Ala Ile Ala Ile Val Gln Leu 100 105 110 Gln Glu Leu Ser Leu Arg Leu Lys Ser Cys Phe Thr Lys Asp Tyr Glu 115 120 125 Glu His Asp Lys Ala Cys Val Arg Thr Phe Tyr Glu Thr Pro Leu Gln 130 135 140 Leu Leu Glu Lys Val Lys Asn Val Phe Asn Glu Thr Lys Asn Leu Leu 145 150 155 160 Asp Lys Asp Trp Asn Ile Phe Ser Lys Asn Cys Asn Asn Ser Phe Ala 165 170 175 Glu Cys Ser Ser Gln Gly His Glu Arg Gln Ser Glu Gly Ser Ser Ser 180 185 190 Pro Gln Leu Gln Glu Ser Val Phe His Leu Leu Val Pro Ser Val Ile 195 200 205 Leu Val Leu Leu Ala Val Gly Gly Leu Leu Phe Tyr Arg Trp Arg Arg 210 215 220 Arg Ser His Gln Glu Pro Gln Arg Ala Asp Ser Pro Leu Glu Gln Pro 225 230 235 240 Glu Gly Ser Pro Leu Thr Gln Asp Asp Arg Gln Val Glu Leu Pro Val 245 250 255 <210> SEQ ID NO 38 <211> LENGTH: 144 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 38 Met Trp Leu Gln Ser Leu Leu Leu Leu Gly Thr Val Ala Cys Ser Ile 1 5 10 15 Ser Ala Pro Ala Arg Ser Pro Ser Pro Ser Thr Gln Pro Trp Glu His 20 25 30 Val Asn Ala Ile Gln Glu Ala Arg Arg Leu Leu Asn Leu Ser Arg Asp 35 40 45 Thr Ala Ala Glu Met Asn Glu Thr Val Glu Val Ile Ser Glu Met Phe 50 55 60 Asp Leu Gln Glu Pro Thr Cys Leu Gln Thr Arg Leu Glu Leu Tyr Lys 65 70 75 80 Gln Gly Leu Arg Gly Ser Leu Thr Lys Leu Lys Gly Pro Leu Thr Met 85 90 95 Met Ala Ser His Tyr Lys Gln His Cys Pro Pro Thr Pro Glu Thr Ser 100 105 110 Cys Ala Thr Gln Ile Ile Thr Phe Glu Ser Phe Lys Glu Asn Leu Lys 115 120 125 Asp Phe Leu Leu Val Ile Pro Phe Asp Cys Trp Glu Pro Val Gln Glu 130 135 140 <210> SEQ ID NO 39 <211> LENGTH: 207 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 39 Met Ala Gly Pro Ala Thr Gln Ser Pro Met Lys Leu Met Ala Leu Gln 1 5 10 15 Leu Leu Leu Trp His Ser Ala Leu Trp Thr Val Gln Glu Ala Thr Pro 20 25 30 Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Cys Leu 35 40 45 Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys 50 55 60 Leu Val Ser Glu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu 65 70 75 80 Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser 85 90 95 Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His 100 105 110 Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile 115 120 125 Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala 130 135 140 Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala 145 150 155 160 Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala 165 170 175 Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser 180 185 190 Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro 195 200 205 <210> SEQ ID NO 40 <211> LENGTH: 204 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 40 Met Ala Gly Pro Ala Thr Gln Ser Pro Met Lys Leu Met Ala Leu Gln 1 5 10 15 Leu Leu Leu Trp His Ser Ala Leu Trp Thr Val Gln Glu Ala Thr Pro 20 25 30 Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Cys Leu 35 40 45 Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys 50 55 60 Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu 65 70 75 80 Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser 85 90 95 Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu 100 105 110 Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu 115 120 125 Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala 130 135 140 Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu 145 150 155 160 Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg 165 170 175 Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu 180 185 190 Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro 195 200 <210> SEQ ID NO 41 <211> LENGTH: 200 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 41 Met Ser Pro Glu Pro Ala Leu Ser Pro Ala Leu Gln Leu Leu Leu Trp 1 5 10 15 His Ser Ala Leu Trp Thr Val Gln Glu Ala Thr Pro Leu Gly Pro Ala 20 25 30 Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Cys Leu Glu Gln Val Arg 35 40 45 Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr 50 55 60 Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu 65 70 75 80 Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln 85 90 95 Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln 100 105 110 Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr 115 120 125 Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp 130 135 140 Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro Thr Gln 145 150 155 160 Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly 165 170 175 Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg 180 185 190 Val Leu Arg His Leu Ala Gln Pro 195 200 <210> SEQ ID NO 42 <211> LENGTH: 393 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 42 Met Glu Glu Pro Gln Ser Asp Pro Ser Val Glu Pro Pro Leu Ser Gln 1 5 10 15 Glu Thr Phe Ser Asp Leu Trp Lys Leu Leu Pro Glu Asn Asn Val Leu 20 25 30 Ser Pro Leu Pro Ser Gln Ala Met Asp Asp Leu Met Leu Ser Pro Asp 35 40 45 Asp Ile Glu Gln Trp Phe Thr Glu Asp Pro Gly Pro Asp Glu Ala Pro 50 55 60 Arg Met Pro Glu Ala Ala Pro Pro Val Ala Pro Ala Pro Ala Ala Pro 65 70 75 80 Thr Pro Ala Ala Pro Ala Pro Ala Pro Ser Trp Pro Leu Ser Ser Ser 85 90 95 Val Pro Ser Gln Lys Thr Tyr Gln Gly Ser Tyr Gly Phe Arg Leu Gly 100 105 110 Phe Leu His Ser Gly Thr Ala Lys Ser Val Thr Cys Thr Tyr Ser Pro 115 120 125

Ala Leu Asn Lys Met Phe Cys Gln Leu Ala Lys Thr Cys Pro Val Gln 130 135 140 Leu Trp Val Asp Ser Thr Pro Pro Pro Gly Thr Arg Val Arg Ala Met 145 150 155 160 Ala Ile Tyr Lys Gln Ser Gln His Met Thr Glu Val Val Arg Arg Cys 165 170 175 Pro His His Glu Arg Cys Ser Asp Ser Asp Gly Leu Ala Pro Pro Gln 180 185 190 His Leu Ile Arg Val Glu Gly Asn Leu Arg Val Glu Tyr Leu Asp Asp 195 200 205 Arg Asn Thr Phe Arg His Ser Val Val Val Pro Tyr Glu Pro Pro Glu 210 215 220 Val Gly Ser Asp Cys Thr Thr Ile His Tyr Asn Tyr Met Cys Asn Ser 225 230 235 240 Ser Cys Met Gly Gly Met Asn Arg Arg Pro Ile Leu Thr Ile Ile Thr 245 250 255 Leu Glu Asp Ser Ser Gly Asn Leu Leu Gly Arg Asn Ser Phe Glu Val 260 265 270 Arg Val Cys Ala Cys Pro Gly Arg Asp Arg Arg Thr Glu Glu Glu Asn 275 280 285 Leu Arg Lys Lys Gly Glu Pro His His Glu Leu Pro Pro Gly Ser Thr 290 295 300 Lys Arg Ala Leu Pro Asn Asn Thr Ser Ser Ser Pro Gln Pro Lys Lys 305 310 315 320 Lys Pro Leu Asp Gly Glu Tyr Phe Thr Leu Gln Ile Arg Gly Arg Glu 325 330 335 Arg Phe Glu Met Phe Arg Glu Leu Asn Glu Ala Leu Glu Leu Lys Asp 340 345 350 Ala Gln Ala Gly Lys Glu Pro Gly Gly Ser Arg Ala His Ser Ser His 355 360 365 Leu Lys Ser Lys Lys Gly Gln Ser Thr Ser Arg His Lys Lys Leu Met 370 375 380 Phe Lys Thr Glu Gly Pro Asp Ser Asp 385 390 <210> SEQ ID NO 43 <211> LENGTH: 393 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 43 Met Glu Glu Pro Gln Ser Asp Pro Ser Val Glu Pro Pro Leu Ser Gln 1 5 10 15 Glu Thr Phe Ser Asp Leu Trp Lys Leu Leu Pro Glu Asn Asn Val Leu 20 25 30 Ser Pro Leu Pro Ser Gln Ala Met Asp Asp Leu Met Leu Ser Pro Asp 35 40 45 Asp Ile Glu Gln Trp Phe Thr Glu Asp Pro Gly Pro Asp Glu Ala Pro 50 55 60 Arg Met Pro Glu Ala Ala Pro Pro Val Ala Pro Ala Pro Ala Ala Pro 65 70 75 80 Thr Pro Ala Ala Pro Ala Pro Ala Pro Ser Trp Pro Leu Ser Ser Ser 85 90 95 Val Pro Ser Gln Lys Thr Tyr Gln Gly Ser Tyr Gly Phe Arg Leu Gly 100 105 110 Phe Leu His Ser Gly Thr Ala Lys Ser Val Thr Cys Thr Tyr Ser Pro 115 120 125 Ala Leu Asn Lys Met Phe Cys Gln Leu Ala Lys Thr Cys Pro Val Gln 130 135 140 Leu Trp Val Asp Ser Thr Pro Pro Pro Gly Thr Arg Val Arg Ala Met 145 150 155 160 Ala Ile Tyr Lys Gln Ser Gln His Met Thr Glu Val Val Arg Arg Cys 165 170 175 Pro His His Glu Arg Cys Ser Asp Ser Asp Gly Leu Ala Pro Pro Gln 180 185 190 His Leu Ile Arg Val Glu Gly Asn Leu Arg Val Glu Tyr Leu Asp Asp 195 200 205 Arg Asn Thr Phe Arg His Ser Val Val Val Pro Tyr Glu Pro Pro Glu 210 215 220 Val Gly Ser Asp Cys Thr Thr Ile His Tyr Asn Tyr Met Cys Asn Ser 225 230 235 240 Ser Cys Met Gly Gly Met Asn Arg Arg Pro Ile Leu Thr Ile Ile Thr 245 250 255 Leu Glu Asp Ser Ser Gly Asn Leu Leu Gly Arg Asn Ser Phe Glu Val 260 265 270 Arg Val Cys Ala Cys Pro Gly Arg Asp Arg Arg Thr Glu Glu Glu Asn 275 280 285 Leu Arg Lys Lys Gly Glu Pro His His Glu Leu Pro Pro Gly Ser Thr 290 295 300 Lys Arg Ala Leu Pro Asn Asn Thr Ser Ser Ser Pro Gln Pro Lys Lys 305 310 315 320 Lys Pro Leu Asp Gly Glu Tyr Phe Thr Leu Gln Ile Arg Gly Arg Glu 325 330 335 Arg Phe Glu Met Phe Arg Glu Leu Asn Glu Ala Leu Glu Leu Lys Asp 340 345 350 Ala Gln Ala Gly Lys Glu Pro Gly Gly Ser Arg Ala His Ser Ser His 355 360 365 Leu Lys Ser Lys Lys Gly Gln Ser Thr Ser Arg His Lys Lys Leu Met 370 375 380 Phe Lys Thr Glu Gly Pro Asp Ser Asp 385 390 <210> SEQ ID NO 44 <211> LENGTH: 341 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 44 Met Glu Glu Pro Gln Ser Asp Pro Ser Val Glu Pro Pro Leu Ser Gln 1 5 10 15 Glu Thr Phe Ser Asp Leu Trp Lys Leu Leu Pro Glu Asn Asn Val Leu 20 25 30 Ser Pro Leu Pro Ser Gln Ala Met Asp Asp Leu Met Leu Ser Pro Asp 35 40 45 Asp Ile Glu Gln Trp Phe Thr Glu Asp Pro Gly Pro Asp Glu Ala Pro 50 55 60 Arg Met Pro Glu Ala Ala Pro Pro Val Ala Pro Ala Pro Ala Ala Pro 65 70 75 80 Thr Pro Ala Ala Pro Ala Pro Ala Pro Ser Trp Pro Leu Ser Ser Ser 85 90 95 Val Pro Ser Gln Lys Thr Tyr Gln Gly Ser Tyr Gly Phe Arg Leu Gly 100 105 110 Phe Leu His Ser Gly Thr Ala Lys Ser Val Thr Cys Thr Tyr Ser Pro 115 120 125 Ala Leu Asn Lys Met Phe Cys Gln Leu Ala Lys Thr Cys Pro Val Gln 130 135 140 Leu Trp Val Asp Ser Thr Pro Pro Pro Gly Thr Arg Val Arg Ala Met 145 150 155 160 Ala Ile Tyr Lys Gln Ser Gln His Met Thr Glu Val Val Arg Arg Cys 165 170 175 Pro His His Glu Arg Cys Ser Asp Ser Asp Gly Leu Ala Pro Pro Gln 180 185 190 His Leu Ile Arg Val Glu Gly Asn Leu Arg Val Glu Tyr Leu Asp Asp 195 200 205 Arg Asn Thr Phe Arg His Ser Val Val Val Pro Tyr Glu Pro Pro Glu 210 215 220 Val Gly Ser Asp Cys Thr Thr Ile His Tyr Asn Tyr Met Cys Asn Ser 225 230 235 240 Ser Cys Met Gly Gly Met Asn Arg Arg Pro Ile Leu Thr Ile Ile Thr 245 250 255 Leu Glu Asp Ser Ser Gly Asn Leu Leu Gly Arg Asn Ser Phe Glu Val 260 265 270 Arg Val Cys Ala Cys Pro Gly Arg Asp Arg Arg Thr Glu Glu Glu Asn 275 280 285 Leu Arg Lys Lys Gly Glu Pro His His Glu Leu Pro Pro Gly Ser Thr 290 295 300 Lys Arg Ala Leu Pro Asn Asn Thr Ser Ser Ser Pro Gln Pro Lys Lys 305 310 315 320 Lys Pro Leu Asp Gly Glu Tyr Phe Thr Leu Gln Asp Gln Thr Ser Phe 325 330 335 Gln Lys Glu Asn Cys 340 <210> SEQ ID NO 45 <211> LENGTH: 346 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 45 Met Glu Glu Pro Gln Ser Asp Pro Ser Val Glu Pro Pro Leu Ser Gln 1 5 10 15 Glu Thr Phe Ser Asp Leu Trp Lys Leu Leu Pro Glu Asn Asn Val Leu 20 25 30 Ser Pro Leu Pro Ser Gln Ala Met Asp Asp Leu Met Leu Ser Pro Asp 35 40 45 Asp Ile Glu Gln Trp Phe Thr Glu Asp Pro Gly Pro Asp Glu Ala Pro 50 55 60 Arg Met Pro Glu Ala Ala Pro Pro Val Ala Pro Ala Pro Ala Ala Pro 65 70 75 80 Thr Pro Ala Ala Pro Ala Pro Ala Pro Ser Trp Pro Leu Ser Ser Ser 85 90 95 Val Pro Ser Gln Lys Thr Tyr Gln Gly Ser Tyr Gly Phe Arg Leu Gly 100 105 110 Phe Leu His Ser Gly Thr Ala Lys Ser Val Thr Cys Thr Tyr Ser Pro 115 120 125 Ala Leu Asn Lys Met Phe Cys Gln Leu Ala Lys Thr Cys Pro Val Gln 130 135 140 Leu Trp Val Asp Ser Thr Pro Pro Pro Gly Thr Arg Val Arg Ala Met 145 150 155 160 Ala Ile Tyr Lys Gln Ser Gln His Met Thr Glu Val Val Arg Arg Cys 165 170 175 Pro His His Glu Arg Cys Ser Asp Ser Asp Gly Leu Ala Pro Pro Gln 180 185 190

His Leu Ile Arg Val Glu Gly Asn Leu Arg Val Glu Tyr Leu Asp Asp 195 200 205 Arg Asn Thr Phe Arg His Ser Val Val Val Pro Tyr Glu Pro Pro Glu 210 215 220 Val Gly Ser Asp Cys Thr Thr Ile His Tyr Asn Tyr Met Cys Asn Ser 225 230 235 240 Ser Cys Met Gly Gly Met Asn Arg Arg Pro Ile Leu Thr Ile Ile Thr 245 250 255 Leu Glu Asp Ser Ser Gly Asn Leu Leu Gly Arg Asn Ser Phe Glu Val 260 265 270 Arg Val Cys Ala Cys Pro Gly Arg Asp Arg Arg Thr Glu Glu Glu Asn 275 280 285 Leu Arg Lys Lys Gly Glu Pro His His Glu Leu Pro Pro Gly Ser Thr 290 295 300 Lys Arg Ala Leu Pro Asn Asn Thr Ser Ser Ser Pro Gln Pro Lys Lys 305 310 315 320 Lys Pro Leu Asp Gly Glu Tyr Phe Thr Leu Gln Met Leu Leu Asp Leu 325 330 335 Arg Trp Cys Tyr Phe Leu Ile Asn Ser Ser 340 345 <210> SEQ ID NO 46 <211> LENGTH: 261 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 46 Met Phe Cys Gln Leu Ala Lys Thr Cys Pro Val Gln Leu Trp Val Asp 1 5 10 15 Ser Thr Pro Pro Pro Gly Thr Arg Val Arg Ala Met Ala Ile Tyr Lys 20 25 30 Gln Ser Gln His Met Thr Glu Val Val Arg Arg Cys Pro His His Glu 35 40 45 Arg Cys Ser Asp Ser Asp Gly Leu Ala Pro Pro Gln His Leu Ile Arg 50 55 60 Val Glu Gly Asn Leu Arg Val Glu Tyr Leu Asp Asp Arg Asn Thr Phe 65 70 75 80 Arg His Ser Val Val Val Pro Tyr Glu Pro Pro Glu Val Gly Ser Asp 85 90 95 Cys Thr Thr Ile His Tyr Asn Tyr Met Cys Asn Ser Ser Cys Met Gly 100 105 110 Gly Met Asn Arg Arg Pro Ile Leu Thr Ile Ile Thr Leu Glu Asp Ser 115 120 125 Ser Gly Asn Leu Leu Gly Arg Asn Ser Phe Glu Val Arg Val Cys Ala 130 135 140 Cys Pro Gly Arg Asp Arg Arg Thr Glu Glu Glu Asn Leu Arg Lys Lys 145 150 155 160 Gly Glu Pro His His Glu Leu Pro Pro Gly Ser Thr Lys Arg Ala Leu 165 170 175 Pro Asn Asn Thr Ser Ser Ser Pro Gln Pro Lys Lys Lys Pro Leu Asp 180 185 190 Gly Glu Tyr Phe Thr Leu Gln Ile Arg Gly Arg Glu Arg Phe Glu Met 195 200 205 Phe Arg Glu Leu Asn Glu Ala Leu Glu Leu Lys Asp Ala Gln Ala Gly 210 215 220 Lys Glu Pro Gly Gly Ser Arg Ala His Ser Ser His Leu Lys Ser Lys 225 230 235 240 Lys Gly Gln Ser Thr Ser Arg His Lys Lys Leu Met Phe Lys Thr Glu 245 250 255 Gly Pro Asp Ser Asp 260 <210> SEQ ID NO 47 <211> LENGTH: 209 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 47 Met Phe Cys Gln Leu Ala Lys Thr Cys Pro Val Gln Leu Trp Val Asp 1 5 10 15 Ser Thr Pro Pro Pro Gly Thr Arg Val Arg Ala Met Ala Ile Tyr Lys 20 25 30 Gln Ser Gln His Met Thr Glu Val Val Arg Arg Cys Pro His His Glu 35 40 45 Arg Cys Ser Asp Ser Asp Gly Leu Ala Pro Pro Gln His Leu Ile Arg 50 55 60 Val Glu Gly Asn Leu Arg Val Glu Tyr Leu Asp Asp Arg Asn Thr Phe 65 70 75 80 Arg His Ser Val Val Val Pro Tyr Glu Pro Pro Glu Val Gly Ser Asp 85 90 95 Cys Thr Thr Ile His Tyr Asn Tyr Met Cys Asn Ser Ser Cys Met Gly 100 105 110 Gly Met Asn Arg Arg Pro Ile Leu Thr Ile Ile Thr Leu Glu Asp Ser 115 120 125 Ser Gly Asn Leu Leu Gly Arg Asn Ser Phe Glu Val Arg Val Cys Ala 130 135 140 Cys Pro Gly Arg Asp Arg Arg Thr Glu Glu Glu Asn Leu Arg Lys Lys 145 150 155 160 Gly Glu Pro His His Glu Leu Pro Pro Gly Ser Thr Lys Arg Ala Leu 165 170 175 Pro Asn Asn Thr Ser Ser Ser Pro Gln Pro Lys Lys Lys Pro Leu Asp 180 185 190 Gly Glu Tyr Phe Thr Leu Gln Asp Gln Thr Ser Phe Gln Lys Glu Asn 195 200 205 Cys <210> SEQ ID NO 48 <211> LENGTH: 214 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 48 Met Phe Cys Gln Leu Ala Lys Thr Cys Pro Val Gln Leu Trp Val Asp 1 5 10 15 Ser Thr Pro Pro Pro Gly Thr Arg Val Arg Ala Met Ala Ile Tyr Lys 20 25 30 Gln Ser Gln His Met Thr Glu Val Val Arg Arg Cys Pro His His Glu 35 40 45 Arg Cys Ser Asp Ser Asp Gly Leu Ala Pro Pro Gln His Leu Ile Arg 50 55 60 Val Glu Gly Asn Leu Arg Val Glu Tyr Leu Asp Asp Arg Asn Thr Phe 65 70 75 80 Arg His Ser Val Val Val Pro Tyr Glu Pro Pro Glu Val Gly Ser Asp 85 90 95 Cys Thr Thr Ile His Tyr Asn Tyr Met Cys Asn Ser Ser Cys Met Gly 100 105 110 Gly Met Asn Arg Arg Pro Ile Leu Thr Ile Ile Thr Leu Glu Asp Ser 115 120 125 Ser Gly Asn Leu Leu Gly Arg Asn Ser Phe Glu Val Arg Val Cys Ala 130 135 140 Cys Pro Gly Arg Asp Arg Arg Thr Glu Glu Glu Asn Leu Arg Lys Lys 145 150 155 160 Gly Glu Pro His His Glu Leu Pro Pro Gly Ser Thr Lys Arg Ala Leu 165 170 175 Pro Asn Asn Thr Ser Ser Ser Pro Gln Pro Lys Lys Lys Pro Leu Asp 180 185 190 Gly Glu Tyr Phe Thr Leu Gln Met Leu Leu Asp Leu Arg Trp Cys Tyr 195 200 205 Phe Leu Ile Asn Ser Ser 210 <210> SEQ ID NO 49 <211> LENGTH: 1237 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 49 Met Asp Ala Lys Ala Arg Asn Cys Leu Leu Gln His Arg Glu Ala Leu 1 5 10 15 Glu Lys Asp Ile Lys Thr Ser Tyr Ile Met Asp His Met Ile Ser Asp 20 25 30 Gly Phe Leu Thr Ile Ser Glu Glu Glu Lys Val Arg Asn Glu Pro Thr 35 40 45 Gln Gln Gln Arg Ala Ala Met Leu Ile Lys Met Ile Leu Lys Lys Asp 50 55 60 Asn Asp Ser Tyr Val Ser Phe Tyr Asn Ala Leu Leu His Glu Gly Tyr 65 70 75 80 Lys Asp Leu Ala Ala Leu Leu His Asp Gly Ile Pro Val Val Ser Ser 85 90 95 Ser Ser Val Arg Thr Val Leu Cys Glu Gly Gly Val Pro Gln Arg Pro 100 105 110 Val Val Phe Val Thr Arg Lys Lys Leu Val Asn Ala Ile Gln Gln Lys 115 120 125 Leu Ser Lys Leu Lys Gly Glu Pro Gly Trp Val Thr Ile His Gly Met 130 135 140 Ala Gly Cys Gly Lys Ser Val Leu Ala Ala Glu Ala Val Arg Asp His 145 150 155 160 Ser Leu Leu Glu Gly Cys Phe Pro Gly Gly Val His Trp Val Ser Val 165 170 175 Gly Lys Gln Asp Lys Ser Gly Leu Leu Met Lys Leu Gln Asn Leu Cys 180 185 190 Thr Arg Leu Asp Gln Asp Glu Ser Phe Ser Gln Arg Leu Pro Leu Asn 195 200 205 Ile Glu Glu Ala Lys Asp Arg Leu Arg Ile Leu Met Leu Arg Lys His 210 215 220 Pro Arg Ser Leu Leu Ile Leu Asp Asp Val Trp Asp Ser Trp Val Leu 225 230 235 240 Lys Ala Phe Asp Ser Gln Cys Gln Ile Leu Leu Thr Thr Arg Asp Lys 245 250 255 Ser Val Thr Asp Ser Val Met Gly Pro Lys Tyr Val Val Pro Val Glu 260 265 270 Ser Ser Leu Gly Lys Glu Lys Gly Leu Glu Ile Leu Ser Leu Phe Val 275 280 285 Asn Met Lys Lys Ala Asp Leu Pro Glu Gln Ala His Ser Ile Ile Lys

290 295 300 Glu Cys Lys Gly Ser Pro Leu Val Val Ser Leu Ile Gly Ala Leu Leu 305 310 315 320 Arg Asp Phe Pro Asn Arg Trp Glu Tyr Tyr Leu Lys Gln Leu Gln Asn 325 330 335 Lys Gln Phe Lys Arg Ile Arg Lys Ser Ser Ser Tyr Asp Tyr Glu Ala 340 345 350 Leu Asp Glu Ala Met Ser Ile Ser Val Glu Met Leu Arg Glu Asp Ile 355 360 365 Lys Asp Tyr Tyr Thr Asp Leu Ser Ile Leu Gln Lys Asp Val Lys Val 370 375 380 Pro Thr Lys Val Leu Cys Ile Leu Trp Asp Met Glu Thr Glu Glu Val 385 390 395 400 Glu Asp Ile Leu Gln Glu Phe Val Asn Lys Ser Leu Leu Phe Cys Asp 405 410 415 Arg Asn Gly Lys Ser Phe Arg Tyr Tyr Leu His Asp Leu Gln Val Asp 420 425 430 Phe Leu Thr Glu Lys Asn Cys Ser Gln Leu Gln Asp Leu His Lys Lys 435 440 445 Ile Ile Thr Gln Phe Gln Arg Tyr His Gln Pro His Thr Leu Ser Pro 450 455 460 Asp Gln Glu Asp Cys Met Tyr Trp Tyr Asn Phe Leu Ala Tyr His Met 465 470 475 480 Ala Ser Ala Lys Met His Lys Glu Leu Cys Ala Leu Met Phe Ser Leu 485 490 495 Asp Trp Ile Lys Ala Lys Thr Glu Leu Val Gly Pro Ala His Leu Ile 500 505 510 His Glu Phe Val Glu Tyr Arg His Ile Leu Asp Glu Lys Asp Cys Ala 515 520 525 Val Ser Glu Asn Phe Gln Glu Phe Leu Ser Leu Asn Gly His Leu Leu 530 535 540 Gly Arg Gln Pro Phe Pro Asn Ile Val Gln Leu Gly Leu Cys Glu Pro 545 550 555 560 Glu Thr Ser Glu Val Tyr Gln Gln Ala Lys Leu Gln Ala Lys Gln Glu 565 570 575 Val Asp Asn Gly Met Leu Tyr Leu Glu Trp Ile Asn Lys Lys Asn Ile 580 585 590 Thr Asn Leu Ser Arg Leu Val Val Arg Pro His Thr Asp Ala Val Tyr 595 600 605 His Ala Cys Phe Ser Glu Asp Gly Gln Arg Ile Ala Ser Cys Gly Ala 610 615 620 Asp Lys Thr Leu Gln Val Phe Lys Ala Glu Thr Gly Glu Lys Leu Leu 625 630 635 640 Glu Ile Lys Ala His Glu Asp Glu Val Leu Cys Cys Ala Phe Ser Thr 645 650 655 Asp Asp Arg Phe Ile Ala Thr Cys Ser Val Asp Lys Lys Val Lys Ile 660 665 670 Trp Asn Ser Met Thr Gly Glu Leu Val His Thr Tyr Asp Glu His Ser 675 680 685 Glu Gln Val Asn Cys Cys His Phe Thr Asn Ser Ser His His Leu Leu 690 695 700 Leu Ala Thr Gly Ser Ser Asp Cys Phe Leu Lys Leu Trp Asp Leu Asn 705 710 715 720 Gln Lys Glu Cys Arg Asn Thr Met Phe Gly His Thr Asn Ser Val Asn 725 730 735 His Cys Arg Phe Ser Pro Asp Asp Lys Leu Leu Ala Ser Cys Ser Ala 740 745 750 Asp Gly Thr Leu Lys Leu Trp Asp Ala Thr Ser Ala Asn Glu Arg Lys 755 760 765 Ser Ile Asn Val Lys Gln Phe Phe Leu Asn Leu Glu Asp Pro Gln Glu 770 775 780 Asp Met Glu Val Ile Val Lys Cys Cys Ser Trp Ser Ala Asp Gly Ala 785 790 795 800 Arg Ile Met Val Ala Ala Lys Asn Lys Ile Phe Leu Phe Asp Ile His 805 810 815 Thr Ser Gly Leu Leu Gly Glu Ile His Thr Gly His His Ser Thr Ile 820 825 830 Gln Tyr Cys Asp Phe Ser Pro Gln Asn His Leu Ala Val Val Ala Leu 835 840 845 Ser Gln Tyr Cys Val Glu Leu Trp Asn Thr Asp Ser Arg Ser Lys Val 850 855 860 Ala Asp Cys Arg Gly His Leu Ser Trp Val His Gly Val Met Phe Ser 865 870 875 880 Pro Asp Gly Ser Ser Phe Leu Thr Ser Ser Asp Asp Gln Thr Ile Arg 885 890 895 Leu Trp Glu Thr Lys Lys Val Cys Lys Asn Ser Ala Val Met Leu Lys 900 905 910 Gln Glu Val Asp Val Val Phe Gln Glu Asn Glu Val Met Val Leu Ala 915 920 925 Val Asp His Ile Arg Arg Leu Gln Leu Ile Asn Gly Arg Thr Gly Gln 930 935 940 Ile Asp Tyr Leu Thr Glu Ala Gln Val Ser Cys Cys Cys Leu Ser Pro 945 950 955 960 His Leu Gln Tyr Ile Ala Phe Gly Asp Glu Asn Gly Ala Ile Glu Ile 965 970 975 Leu Glu Leu Val Asn Asn Arg Ile Phe Gln Ser Arg Phe Gln His Lys 980 985 990 Lys Thr Val Trp His Ile Gln Phe Thr Ala Asp Glu Lys Thr Leu Ile 995 1000 1005 Ser Ser Ser Asp Asp Ala Glu Ile Gln Val Trp Asn Trp Gln Leu Asp 1010 1015 1020 Lys Cys Ile Phe Leu Arg Gly His Gln Glu Thr Val Lys Asp Phe Arg 1025 1030 1035 1040 Leu Leu Lys Asn Ser Arg Leu Leu Ser Trp Ser Phe Asp Gly Thr Val 1045 1050 1055 Lys Val Trp Asn Ile Ile Thr Gly Asn Lys Glu Lys Asp Phe Val Cys 1060 1065 1070 His Gln Gly Thr Val Leu Ser Cys Asp Ile Ser His Asp Ala Thr Lys 1075 1080 1085 Phe Ser Ser Thr Ser Ala Asp Lys Thr Ala Lys Ile Trp Ser Phe Asp 1090 1095 1100 Leu Leu Leu Pro Leu His Glu Leu Arg Gly His Asn Gly Cys Val Arg 1105 1110 1115 1120 Cys Ser Ala Phe Ser Val Asp Ser Thr Leu Leu Ala Thr Gly Asp Asp 1125 1130 1135 Asn Gly Glu Ile Arg Ile Trp Asn Val Ser Asn Gly Glu Leu Leu His 1140 1145 1150 Leu Cys Ala Pro Leu Ser Glu Glu Gly Ala Ala Thr His Gly Gly Trp 1155 1160 1165 Val Thr Asp Leu Cys Phe Ser Pro Asp Gly Lys Met Leu Ile Ser Ala 1170 1175 1180 Gly Gly Tyr Ile Lys Trp Trp Asn Val Val Thr Gly Glu Ser Ser Gln 1185 1190 1195 1200 Thr Phe Tyr Thr Asn Gly Thr Asn Leu Lys Lys Ile His Val Ser Pro 1205 1210 1215 Asp Phe Lys Thr Tyr Val Thr Val Asp Asn Leu Gly Ile Leu Tyr Ile 1220 1225 1230 Leu Gln Thr Leu Glu 1235 <210> SEQ ID NO 50 <211> LENGTH: 1194 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 50 Met Asp Ala Lys Ala Arg Asn Cys Leu Leu Gln His Arg Glu Ala Leu 1 5 10 15 Glu Lys Asp Ile Lys Thr Ser Tyr Ile Met Asp His Met Ile Ser Asp 20 25 30 Gly Phe Leu Thr Ile Ser Glu Glu Glu Lys Val Arg Asn Glu Pro Thr 35 40 45 Gln Gln Gln Arg Ala Ala Met Leu Ile Lys Met Ile Leu Lys Lys Asp 50 55 60 Asn Asp Ser Tyr Val Ser Phe Tyr Asn Ala Leu Leu His Glu Gly Tyr 65 70 75 80 Lys Asp Leu Ala Ala Leu Leu His Asp Gly Ile Pro Val Val Ser Ser 85 90 95 Ser Ser Val Arg Thr Val Leu Cys Glu Gly Gly Val Pro Gln Arg Pro 100 105 110 Val Val Phe Val Thr Arg Lys Lys Leu Val Asn Ala Ile Gln Gln Lys 115 120 125 Leu Ser Lys Leu Lys Gly Glu Pro Gly Trp Val Thr Ile His Gly Met 130 135 140 Ala Gly Cys Gly Lys Ser Val Leu Ala Ala Glu Ala Val Arg Asp His 145 150 155 160 Ser Leu Leu Glu Gly Cys Phe Pro Gly Gly Val His Trp Val Ser Val 165 170 175 Gly Lys Gln Asp Lys Ser Gly Leu Leu Met Lys Leu Gln Asn Leu Cys 180 185 190 Thr Arg Leu Asp Gln Asp Glu Ser Phe Ser Gln Arg Leu Pro Leu Asn 195 200 205 Ile Glu Glu Ala Lys Asp Arg Leu Arg Ile Leu Met Leu Arg Lys His 210 215 220 Pro Arg Ser Leu Leu Ile Leu Asp Asp Val Trp Asp Ser Trp Val Leu 225 230 235 240 Lys Ala Phe Asp Ser Gln Cys Gln Ile Leu Leu Thr Thr Arg Asp Lys 245 250 255 Ser Val Thr Asp Ser Val Met Gly Pro Lys Tyr Val Val Pro Val Glu 260 265 270 Ser Ser Leu Gly Lys Glu Lys Gly Leu Glu Ile Leu Ser Leu Phe Val 275 280 285 Asn Met Lys Lys Ala Asp Leu Pro Glu Gln Ala His Ser Ile Ile Lys 290 295 300 Glu Cys Lys Gly Ser Pro Leu Val Val Ser Leu Ile Gly Ala Leu Leu 305 310 315 320 Arg Asp Phe Pro Asn Arg Trp Glu Tyr Tyr Leu Lys Gln Leu Gln Asn 325 330 335 Lys Gln Phe Lys Arg Ile Arg Lys Ser Ser Ser Tyr Asp Tyr Glu Ala

340 345 350 Leu Asp Glu Ala Met Ser Ile Ser Val Glu Met Leu Arg Glu Asp Ile 355 360 365 Lys Asp Tyr Tyr Thr Asp Leu Ser Ile Leu Gln Lys Asp Val Lys Val 370 375 380 Pro Thr Lys Val Leu Cys Ile Leu Trp Asp Met Glu Thr Glu Glu Val 385 390 395 400 Glu Asp Ile Leu Gln Glu Phe Val Asn Lys Ser Leu Leu Phe Cys Asp 405 410 415 Arg Asn Gly Lys Ser Phe Arg Tyr Tyr Leu His Asp Leu Gln Val Asp 420 425 430 Phe Leu Thr Glu Lys Asn Cys Ser Gln Leu Gln Asp Leu His Lys Lys 435 440 445 Ile Ile Thr Gln Phe Gln Arg Tyr His Gln Pro His Thr Leu Ser Pro 450 455 460 Asp Gln Glu Asp Cys Met Tyr Trp Tyr Asn Phe Leu Ala Tyr His Met 465 470 475 480 Ala Ser Ala Lys Met His Lys Glu Leu Cys Ala Leu Met Phe Ser Leu 485 490 495 Asp Trp Ile Lys Ala Lys Thr Glu Leu Val Gly Pro Ala His Leu Ile 500 505 510 His Glu Phe Val Glu Tyr Arg His Ile Leu Asp Glu Lys Asp Cys Ala 515 520 525 Val Ser Glu Asn Phe Gln Glu Phe Leu Ser Leu Asn Gly His Leu Leu 530 535 540 Gly Arg Gln Pro Phe Pro Asn Ile Val Gln Leu Gly Leu Cys Glu Pro 545 550 555 560 Glu Thr Ser Glu Val Tyr Gln Gln Ala Lys Leu Gln Ala Lys Gln Glu 565 570 575 Val Asp Asn Gly Met Leu Tyr Leu Glu Trp Ile Asn Lys Lys Asn Ile 580 585 590 Thr Asn Leu Ser Arg Leu Val Val Arg Pro His Thr Asp Ala Val Tyr 595 600 605 His Ala Cys Phe Ser Glu Asp Gly Gln Arg Ile Ala Ser Cys Gly Ala 610 615 620 Asp Lys Thr Leu Gln Val Phe Lys Ala Glu Thr Gly Glu Lys Leu Leu 625 630 635 640 Glu Ile Lys Ala His Glu Asp Glu Val Leu Cys Cys Ala Phe Ser Thr 645 650 655 Asp Asp Arg Phe Ile Ala Thr Cys Ser Val Asp Lys Lys Val Lys Ile 660 665 670 Trp Asn Ser Met Thr Gly Glu Leu Val His Thr Tyr Asp Glu His Ser 675 680 685 Glu Gln Val Asn Cys Cys His Phe Thr Asn Ser Ser His His Leu Leu 690 695 700 Leu Ala Thr Gly Ser Ser Asp Cys Phe Leu Lys Leu Trp Asp Leu Asn 705 710 715 720 Gln Lys Glu Cys Arg Asn Thr Met Phe Gly His Thr Asn Ser Val Asn 725 730 735 His Cys Arg Phe Ser Pro Asp Asp Lys Leu Leu Ala Ser Cys Ser Ala 740 745 750 Asp Gly Thr Leu Lys Leu Trp Asp Ala Thr Ser Ala Asn Glu Arg Lys 755 760 765 Ser Ile Asn Val Lys Gln Phe Phe Leu Asn Leu Glu Asp Pro Gln Glu 770 775 780 Asp Met Glu Val Ile Val Lys Cys Cys Ser Trp Ser Ala Asp Gly Ala 785 790 795 800 Arg Ile Met Val Ala Ala Lys Asn Lys Ile Phe Leu Trp Asn Thr Asp 805 810 815 Ser Arg Ser Lys Val Ala Asp Cys Arg Gly His Leu Ser Trp Val His 820 825 830 Gly Val Met Phe Ser Pro Asp Gly Ser Ser Phe Leu Thr Ser Ser Asp 835 840 845 Asp Gln Thr Ile Arg Leu Trp Glu Thr Lys Lys Val Cys Lys Asn Ser 850 855 860 Ala Val Met Leu Lys Gln Glu Val Asp Val Val Phe Gln Glu Asn Glu 865 870 875 880 Val Met Val Leu Ala Val Asp His Ile Arg Arg Leu Gln Leu Ile Asn 885 890 895 Gly Arg Thr Gly Gln Ile Asp Tyr Leu Thr Glu Ala Gln Val Ser Cys 900 905 910 Cys Cys Leu Ser Pro His Leu Gln Tyr Ile Ala Phe Gly Asp Glu Asn 915 920 925 Gly Ala Ile Glu Ile Leu Glu Leu Val Asn Asn Arg Ile Phe Gln Ser 930 935 940 Arg Phe Gln His Lys Lys Thr Val Trp His Ile Gln Phe Thr Ala Asp 945 950 955 960 Glu Lys Thr Leu Ile Ser Ser Ser Asp Asp Ala Glu Ile Gln Val Trp 965 970 975 Asn Trp Gln Leu Asp Lys Cys Ile Phe Leu Arg Gly His Gln Glu Thr 980 985 990 Val Lys Asp Phe Arg Leu Leu Lys Asn Ser Arg Leu Leu Ser Trp Ser 995 1000 1005 Phe Asp Gly Thr Val Lys Val Trp Asn Ile Ile Thr Gly Asn Lys Glu 1010 1015 1020 Lys Asp Phe Val Cys His Gln Gly Thr Val Leu Ser Cys Asp Ile Ser 1025 1030 1035 1040 His Asp Ala Thr Lys Phe Ser Ser Thr Ser Ala Asp Lys Thr Ala Lys 1045 1050 1055 Ile Trp Ser Phe Asp Leu Leu Leu Pro Leu His Glu Leu Arg Gly His 1060 1065 1070 Asn Gly Cys Val Arg Cys Ser Ala Phe Ser Val Asp Ser Thr Leu Leu 1075 1080 1085 Ala Thr Gly Asp Asp Asn Gly Glu Ile Arg Ile Trp Asn Val Ser Asn 1090 1095 1100 Gly Glu Leu Leu His Leu Cys Ala Pro Leu Ser Glu Glu Gly Ala Ala 1105 1110 1115 1120 Thr His Gly Gly Trp Val Thr Asp Leu Cys Phe Ser Pro Asp Gly Lys 1125 1130 1135 Met Leu Ile Ser Ala Gly Gly Tyr Ile Lys Trp Trp Asn Val Val Thr 1140 1145 1150 Gly Glu Ser Ser Gln Thr Phe Tyr Thr Asn Gly Thr Asn Leu Lys Lys 1155 1160 1165 Ile His Val Ser Pro Asp Phe Lys Thr Tyr Val Thr Val Asp Asn Leu 1170 1175 1180 Gly Ile Leu Tyr Ile Leu Gln Thr Leu Glu 1185 1190 <210> SEQ ID NO 51 <211> LENGTH: 1248 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 51 Met Asp Ala Lys Ala Arg Asn Cys Leu Leu Gln His Arg Glu Ala Leu 1 5 10 15 Glu Lys Asp Ile Lys Thr Ser Tyr Ile Met Asp His Met Ile Ser Asp 20 25 30 Gly Phe Leu Thr Ile Ser Glu Glu Glu Lys Val Arg Asn Glu Pro Thr 35 40 45 Gln Gln Gln Arg Ala Ala Met Leu Ile Lys Met Ile Leu Lys Lys Asp 50 55 60 Asn Asp Ser Tyr Val Ser Phe Tyr Asn Ala Leu Leu His Glu Gly Tyr 65 70 75 80 Lys Asp Leu Ala Ala Leu Leu His Asp Gly Ile Pro Val Val Ser Ser 85 90 95 Ser Ser Gly Lys Asp Ser Val Ser Gly Ile Thr Ser Tyr Val Arg Thr 100 105 110 Val Leu Cys Glu Gly Gly Val Pro Gln Arg Pro Val Val Phe Val Thr 115 120 125 Arg Lys Lys Leu Val Asn Ala Ile Gln Gln Lys Leu Ser Lys Leu Lys 130 135 140 Gly Glu Pro Gly Trp Val Thr Ile His Gly Met Ala Gly Cys Gly Lys 145 150 155 160 Ser Val Leu Ala Ala Glu Ala Val Arg Asp His Ser Leu Leu Glu Gly 165 170 175 Cys Phe Pro Gly Gly Val His Trp Val Ser Val Gly Lys Gln Asp Lys 180 185 190 Ser Gly Leu Leu Met Lys Leu Gln Asn Leu Cys Thr Arg Leu Asp Gln 195 200 205 Asp Glu Ser Phe Ser Gln Arg Leu Pro Leu Asn Ile Glu Glu Ala Lys 210 215 220 Asp Arg Leu Arg Ile Leu Met Leu Arg Lys His Pro Arg Ser Leu Leu 225 230 235 240 Ile Leu Asp Asp Val Trp Asp Ser Trp Val Leu Lys Ala Phe Asp Ser 245 250 255 Gln Cys Gln Ile Leu Leu Thr Thr Arg Asp Lys Ser Val Thr Asp Ser 260 265 270 Val Met Gly Pro Lys Tyr Val Val Pro Val Glu Ser Ser Leu Gly Lys 275 280 285 Glu Lys Gly Leu Glu Ile Leu Ser Leu Phe Val Asn Met Lys Lys Ala 290 295 300 Asp Leu Pro Glu Gln Ala His Ser Ile Ile Lys Glu Cys Lys Gly Ser 305 310 315 320 Pro Leu Val Val Ser Leu Ile Gly Ala Leu Leu Arg Asp Phe Pro Asn 325 330 335 Arg Trp Glu Tyr Tyr Leu Lys Gln Leu Gln Asn Lys Gln Phe Lys Arg 340 345 350 Ile Arg Lys Ser Ser Ser Tyr Asp Tyr Glu Ala Leu Asp Glu Ala Met 355 360 365 Ser Ile Ser Val Glu Met Leu Arg Glu Asp Ile Lys Asp Tyr Tyr Thr 370 375 380 Asp Leu Ser Ile Leu Gln Lys Asp Val Lys Val Pro Thr Lys Val Leu 385 390 395 400 Cys Ile Leu Trp Asp Met Glu Thr Glu Glu Val Glu Asp Ile Leu Gln 405 410 415 Glu Phe Val Asn Lys Ser Leu Leu Phe Cys Asp Arg Asn Gly Lys Ser 420 425 430 Phe Arg Tyr Tyr Leu His Asp Leu Gln Val Asp Phe Leu Thr Glu Lys

435 440 445 Asn Cys Ser Gln Leu Gln Asp Leu His Lys Lys Ile Ile Thr Gln Phe 450 455 460 Gln Arg Tyr His Gln Pro His Thr Leu Ser Pro Asp Gln Glu Asp Cys 465 470 475 480 Met Tyr Trp Tyr Asn Phe Leu Ala Tyr His Met Ala Ser Ala Lys Met 485 490 495 His Lys Glu Leu Cys Ala Leu Met Phe Ser Leu Asp Trp Ile Lys Ala 500 505 510 Lys Thr Glu Leu Val Gly Pro Ala His Leu Ile His Glu Phe Val Glu 515 520 525 Tyr Arg His Ile Leu Asp Glu Lys Asp Cys Ala Val Ser Glu Asn Phe 530 535 540 Gln Glu Phe Leu Ser Leu Asn Gly His Leu Leu Gly Arg Gln Pro Phe 545 550 555 560 Pro Asn Ile Val Gln Leu Gly Leu Cys Glu Pro Glu Thr Ser Glu Val 565 570 575 Tyr Gln Gln Ala Lys Leu Gln Ala Lys Gln Glu Val Asp Asn Gly Met 580 585 590 Leu Tyr Leu Glu Trp Ile Asn Lys Lys Asn Ile Thr Asn Leu Ser Arg 595 600 605 Leu Val Val Arg Pro His Thr Asp Ala Val Tyr His Ala Cys Phe Ser 610 615 620 Glu Asp Gly Gln Arg Ile Ala Ser Cys Gly Ala Asp Lys Thr Leu Gln 625 630 635 640 Val Phe Lys Ala Glu Thr Gly Glu Lys Leu Leu Glu Ile Lys Ala His 645 650 655 Glu Asp Glu Val Leu Cys Cys Ala Phe Ser Thr Asp Asp Arg Phe Ile 660 665 670 Ala Thr Cys Ser Val Asp Lys Lys Val Lys Ile Trp Asn Ser Met Thr 675 680 685 Gly Glu Leu Val His Thr Tyr Asp Glu His Ser Glu Gln Val Asn Cys 690 695 700 Cys His Phe Thr Asn Ser Ser His His Leu Leu Leu Ala Thr Gly Ser 705 710 715 720 Ser Asp Cys Phe Leu Lys Leu Trp Asp Leu Asn Gln Lys Glu Cys Arg 725 730 735 Asn Thr Met Phe Gly His Thr Asn Ser Val Asn His Cys Arg Phe Ser 740 745 750 Pro Asp Asp Lys Leu Leu Ala Ser Cys Ser Ala Asp Gly Thr Leu Lys 755 760 765 Leu Trp Asp Ala Thr Ser Ala Asn Glu Arg Lys Ser Ile Asn Val Lys 770 775 780 Gln Phe Phe Leu Asn Leu Glu Asp Pro Gln Glu Asp Met Glu Val Ile 785 790 795 800 Val Lys Cys Cys Ser Trp Ser Ala Asp Gly Ala Arg Ile Met Val Ala 805 810 815 Ala Lys Asn Lys Ile Phe Leu Phe Asp Ile His Thr Ser Gly Leu Leu 820 825 830 Gly Glu Ile His Thr Gly His His Ser Thr Ile Gln Tyr Cys Asp Phe 835 840 845 Ser Pro Gln Asn His Leu Ala Val Val Ala Leu Ser Gln Tyr Cys Val 850 855 860 Glu Leu Trp Asn Thr Asp Ser Arg Ser Lys Val Ala Asp Cys Arg Gly 865 870 875 880 His Leu Ser Trp Val His Gly Val Met Phe Ser Pro Asp Gly Ser Ser 885 890 895 Phe Leu Thr Ser Ser Asp Asp Gln Thr Ile Arg Leu Trp Glu Thr Lys 900 905 910 Lys Val Cys Lys Asn Ser Ala Val Met Leu Lys Gln Glu Val Asp Val 915 920 925 Val Phe Gln Glu Asn Glu Val Met Val Leu Ala Val Asp His Ile Arg 930 935 940 Arg Leu Gln Leu Ile Asn Gly Arg Thr Gly Gln Ile Asp Tyr Leu Thr 945 950 955 960 Glu Ala Gln Val Ser Cys Cys Cys Leu Ser Pro His Leu Gln Tyr Ile 965 970 975 Ala Phe Gly Asp Glu Asn Gly Ala Ile Glu Ile Leu Glu Leu Val Asn 980 985 990 Asn Arg Ile Phe Gln Ser Arg Phe Gln His Lys Lys Thr Val Trp His 995 1000 1005 Ile Gln Phe Thr Ala Asp Glu Lys Thr Leu Ile Ser Ser Ser Asp Asp 1010 1015 1020 Ala Glu Ile Gln Val Trp Asn Trp Gln Leu Asp Lys Cys Ile Phe Leu 1025 1030 1035 1040 Arg Gly His Gln Glu Thr Val Lys Asp Phe Arg Leu Leu Lys Asn Ser 1045 1050 1055 Arg Leu Leu Ser Trp Ser Phe Asp Gly Thr Val Lys Val Trp Asn Ile 1060 1065 1070 Ile Thr Gly Asn Lys Glu Lys Asp Phe Val Cys His Gln Gly Thr Val 1075 1080 1085 Leu Ser Cys Asp Ile Ser His Asp Ala Thr Lys Phe Ser Ser Thr Ser 1090 1095 1100 Ala Asp Lys Thr Ala Lys Ile Trp Ser Phe Asp Leu Leu Leu Pro Leu 1105 1110 1115 1120 His Glu Leu Arg Gly His Asn Gly Cys Val Arg Cys Ser Ala Phe Ser 1125 1130 1135 Val Asp Ser Thr Leu Leu Ala Thr Gly Asp Asp Asn Gly Glu Ile Arg 1140 1145 1150 Ile Trp Asn Val Ser Asn Gly Glu Leu Leu His Leu Cys Ala Pro Leu 1155 1160 1165 Ser Glu Glu Gly Ala Ala Thr His Gly Gly Trp Val Thr Asp Leu Cys 1170 1175 1180 Phe Ser Pro Asp Gly Lys Met Leu Ile Ser Ala Gly Gly Tyr Ile Lys 1185 1190 1195 1200 Trp Trp Asn Val Val Thr Gly Glu Ser Ser Gln Thr Phe Tyr Thr Asn 1205 1210 1215 Gly Thr Asn Leu Lys Lys Ile His Val Ser Pro Asp Phe Lys Thr Tyr 1220 1225 1230 Val Thr Val Asp Asn Leu Gly Ile Leu Tyr Ile Leu Gln Thr Leu Glu 1235 1240 1245 <210> SEQ ID NO 52 <211> LENGTH: 1205 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 52 Met Asp Ala Lys Ala Arg Asn Cys Leu Leu Gln His Arg Glu Ala Leu 1 5 10 15 Glu Lys Asp Ile Lys Thr Ser Tyr Ile Met Asp His Met Ile Ser Asp 20 25 30 Gly Phe Leu Thr Ile Ser Glu Glu Glu Lys Val Arg Asn Glu Pro Thr 35 40 45 Gln Gln Gln Arg Ala Ala Met Leu Ile Lys Met Ile Leu Lys Lys Asp 50 55 60 Asn Asp Ser Tyr Val Ser Phe Tyr Asn Ala Leu Leu His Glu Gly Tyr 65 70 75 80 Lys Asp Leu Ala Ala Leu Leu His Asp Gly Ile Pro Val Val Ser Ser 85 90 95 Ser Ser Gly Lys Asp Ser Val Ser Gly Ile Thr Ser Tyr Val Arg Thr 100 105 110 Val Leu Cys Glu Gly Gly Val Pro Gln Arg Pro Val Val Phe Val Thr 115 120 125 Arg Lys Lys Leu Val Asn Ala Ile Gln Gln Lys Leu Ser Lys Leu Lys 130 135 140 Gly Glu Pro Gly Trp Val Thr Ile His Gly Met Ala Gly Cys Gly Lys 145 150 155 160 Ser Val Leu Ala Ala Glu Ala Val Arg Asp His Ser Leu Leu Glu Gly 165 170 175 Cys Phe Pro Gly Gly Val His Trp Val Ser Val Gly Lys Gln Asp Lys 180 185 190 Ser Gly Leu Leu Met Lys Leu Gln Asn Leu Cys Thr Arg Leu Asp Gln 195 200 205 Asp Glu Ser Phe Ser Gln Arg Leu Pro Leu Asn Ile Glu Glu Ala Lys 210 215 220 Asp Arg Leu Arg Ile Leu Met Leu Arg Lys His Pro Arg Ser Leu Leu 225 230 235 240 Ile Leu Asp Asp Val Trp Asp Ser Trp Val Leu Lys Ala Phe Asp Ser 245 250 255 Gln Cys Gln Ile Leu Leu Thr Thr Arg Asp Lys Ser Val Thr Asp Ser 260 265 270 Val Met Gly Pro Lys Tyr Val Val Pro Val Glu Ser Ser Leu Gly Lys 275 280 285 Glu Lys Gly Leu Glu Ile Leu Ser Leu Phe Val Asn Met Lys Lys Ala 290 295 300 Asp Leu Pro Glu Gln Ala His Ser Ile Ile Lys Glu Cys Lys Gly Ser 305 310 315 320 Pro Leu Val Val Ser Leu Ile Gly Ala Leu Leu Arg Asp Phe Pro Asn 325 330 335 Arg Trp Glu Tyr Tyr Leu Lys Gln Leu Gln Asn Lys Gln Phe Lys Arg 340 345 350 Ile Arg Lys Ser Ser Ser Tyr Asp Tyr Glu Ala Leu Asp Glu Ala Met 355 360 365 Ser Ile Ser Val Glu Met Leu Arg Glu Asp Ile Lys Asp Tyr Tyr Thr 370 375 380 Asp Leu Ser Ile Leu Gln Lys Asp Val Lys Val Pro Thr Lys Val Leu 385 390 395 400 Cys Ile Leu Trp Asp Met Glu Thr Glu Glu Val Glu Asp Ile Leu Gln 405 410 415 Glu Phe Val Asn Lys Ser Leu Leu Phe Cys Asp Arg Asn Gly Lys Ser 420 425 430 Phe Arg Tyr Tyr Leu His Asp Leu Gln Val Asp Phe Leu Thr Glu Lys 435 440 445 Asn Cys Ser Gln Leu Gln Asp Leu His Lys Lys Ile Ile Thr Gln Phe 450 455 460 Gln Arg Tyr His Gln Pro His Thr Leu Ser Pro Asp Gln Glu Asp Cys 465 470 475 480 Met Tyr Trp Tyr Asn Phe Leu Ala Tyr His Met Ala Ser Ala Lys Met

485 490 495 His Lys Glu Leu Cys Ala Leu Met Phe Ser Leu Asp Trp Ile Lys Ala 500 505 510 Lys Thr Glu Leu Val Gly Pro Ala His Leu Ile His Glu Phe Val Glu 515 520 525 Tyr Arg His Ile Leu Asp Glu Lys Asp Cys Ala Val Ser Glu Asn Phe 530 535 540 Gln Glu Phe Leu Ser Leu Asn Gly His Leu Leu Gly Arg Gln Pro Phe 545 550 555 560 Pro Asn Ile Val Gln Leu Gly Leu Cys Glu Pro Glu Thr Ser Glu Val 565 570 575 Tyr Gln Gln Ala Lys Leu Gln Ala Lys Gln Glu Val Asp Asn Gly Met 580 585 590 Leu Tyr Leu Glu Trp Ile Asn Lys Lys Asn Ile Thr Asn Leu Ser Arg 595 600 605 Leu Val Val Arg Pro His Thr Asp Ala Val Tyr His Ala Cys Phe Ser 610 615 620 Glu Asp Gly Gln Arg Ile Ala Ser Cys Gly Ala Asp Lys Thr Leu Gln 625 630 635 640 Val Phe Lys Ala Glu Thr Gly Glu Lys Leu Leu Glu Ile Lys Ala His 645 650 655 Glu Asp Glu Val Leu Cys Cys Ala Phe Ser Thr Asp Asp Arg Phe Ile 660 665 670 Ala Thr Cys Ser Val Asp Lys Lys Val Lys Ile Trp Asn Ser Met Thr 675 680 685 Gly Glu Leu Val His Thr Tyr Asp Glu His Ser Glu Gln Val Asn Cys 690 695 700 Cys His Phe Thr Asn Ser Ser His His Leu Leu Leu Ala Thr Gly Ser 705 710 715 720 Ser Asp Cys Phe Leu Lys Leu Trp Asp Leu Asn Gln Lys Glu Cys Arg 725 730 735 Asn Thr Met Phe Gly His Thr Asn Ser Val Asn His Cys Arg Phe Ser 740 745 750 Pro Asp Asp Lys Leu Leu Ala Ser Cys Ser Ala Asp Gly Thr Leu Lys 755 760 765 Leu Trp Asp Ala Thr Ser Ala Asn Glu Arg Lys Ser Ile Asn Val Lys 770 775 780 Gln Phe Phe Leu Asn Leu Glu Asp Pro Gln Glu Asp Met Glu Val Ile 785 790 795 800 Val Lys Cys Cys Ser Trp Ser Ala Asp Gly Ala Arg Ile Met Val Ala 805 810 815 Ala Lys Asn Lys Ile Phe Leu Trp Asn Thr Asp Ser Arg Ser Lys Val 820 825 830 Ala Asp Cys Arg Gly His Leu Ser Trp Val His Gly Val Met Phe Ser 835 840 845 Pro Asp Gly Ser Ser Phe Leu Thr Ser Ser Asp Asp Gln Thr Ile Arg 850 855 860 Leu Trp Glu Thr Lys Lys Val Cys Lys Asn Ser Ala Val Met Leu Lys 865 870 875 880 Gln Glu Val Asp Val Val Phe Gln Glu Asn Glu Val Met Val Leu Ala 885 890 895 Val Asp His Ile Arg Arg Leu Gln Leu Ile Asn Gly Arg Thr Gly Gln 900 905 910 Ile Asp Tyr Leu Thr Glu Ala Gln Val Ser Cys Cys Cys Leu Ser Pro 915 920 925 His Leu Gln Tyr Ile Ala Phe Gly Asp Glu Asn Gly Ala Ile Glu Ile 930 935 940 Leu Glu Leu Val Asn Asn Arg Ile Phe Gln Ser Arg Phe Gln His Lys 945 950 955 960 Lys Thr Val Trp His Ile Gln Phe Thr Ala Asp Glu Lys Thr Leu Ile 965 970 975 Ser Ser Ser Asp Asp Ala Glu Ile Gln Val Trp Asn Trp Gln Leu Asp 980 985 990 Lys Cys Ile Phe Leu Arg Gly His Gln Glu Thr Val Lys Asp Phe Arg 995 1000 1005 Leu Leu Lys Asn Ser Arg Leu Leu Ser Trp Ser Phe Asp Gly Thr Val 1010 1015 1020 Lys Val Trp Asn Ile Ile Thr Gly Asn Lys Glu Lys Asp Phe Val Cys 1025 1030 1035 1040 His Gln Gly Thr Val Leu Ser Cys Asp Ile Ser His Asp Ala Thr Lys 1045 1050 1055 Phe Ser Ser Thr Ser Ala Asp Lys Thr Ala Lys Ile Trp Ser Phe Asp 1060 1065 1070 Leu Leu Leu Pro Leu His Glu Leu Arg Gly His Asn Gly Cys Val Arg 1075 1080 1085 Cys Ser Ala Phe Ser Val Asp Ser Thr Leu Leu Ala Thr Gly Asp Asp 1090 1095 1100 Asn Gly Glu Ile Arg Ile Trp Asn Val Ser Asn Gly Glu Leu Leu His 1105 1110 1115 1120 Leu Cys Ala Pro Leu Ser Glu Glu Gly Ala Ala Thr His Gly Gly Trp 1125 1130 1135 Val Thr Asp Leu Cys Phe Ser Pro Asp Gly Lys Met Leu Ile Ser Ala 1140 1145 1150 Gly Gly Tyr Ile Lys Trp Trp Asn Val Val Thr Gly Glu Ser Ser Gln 1155 1160 1165 Thr Phe Tyr Thr Asn Gly Thr Asn Leu Lys Lys Ile His Val Ser Pro 1170 1175 1180 Asp Phe Lys Thr Tyr Val Thr Val Asp Asn Leu Gly Ile Leu Tyr Ile 1185 1190 1195 1200 Leu Gln Thr Leu Glu 1205 <210> SEQ ID NO 53 <211> LENGTH: 338 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 53 Met Asp Ala Lys Ala Arg Asn Cys Leu Leu Gln His Arg Glu Ala Leu 1 5 10 15 Glu Lys Asp Ile Lys Thr Ser Tyr Ile Met Asp His Met Ile Ser Asp 20 25 30 Gly Phe Leu Thr Ile Ser Glu Glu Glu Lys Val Arg Asn Glu Pro Thr 35 40 45 Gln Gln Gln Arg Ala Ala Met Leu Ile Lys Met Ile Leu Lys Lys Asp 50 55 60 Asn Asp Ser Tyr Val Ser Phe Tyr Asn Ala Leu Leu His Glu Gly Tyr 65 70 75 80 Lys Asp Leu Ala Ala Leu Leu His Asp Gly Ile Pro Val Val Ser Ser 85 90 95 Ser Ser Gly Lys Asp Ser Val Ser Gly Ile Thr Ser Tyr Val Arg Thr 100 105 110 Val Leu Cys Glu Gly Gly Val Pro Gln Arg Pro Val Val Phe Val Thr 115 120 125 Arg Lys Lys Leu Val Asn Ala Ile Gln Gln Lys Leu Ser Lys Leu Lys 130 135 140 Gly Glu Pro Gly Trp Val Thr Ile His Gly Met Ala Gly Cys Gly Lys 145 150 155 160 Ser Val Leu Ala Ala Glu Ala Val Arg Asp His Ser Leu Leu Glu Gly 165 170 175 Cys Phe Pro Gly Gly Val His Trp Val Ser Val Gly Lys Gln Asp Lys 180 185 190 Ser Gly Leu Leu Met Lys Leu Gln Asn Leu Cys Thr Arg Leu Asp Gln 195 200 205 Asp Glu Ser Phe Ser Gln Arg Leu Pro Leu Asn Ile Glu Glu Ala Lys 210 215 220 Asp Arg Leu Arg Ile Leu Met Leu Arg Lys His Pro Arg Ser Leu Leu 225 230 235 240 Ile Leu Asp Asp Val Trp Asp Ser Trp Val Leu Lys Ala Phe Asp Ser 245 250 255 Gln Cys Gln Ile Leu Leu Thr Thr Arg Asp Lys Ser Val Thr Asp Ser 260 265 270 Val Met Gly Pro Lys Tyr Val Val Pro Val Glu Ser Ser Leu Gly Lys 275 280 285 Glu Lys Gly Leu Glu Ile Leu Ser Leu Phe Val Asn Met Lys Lys Ala 290 295 300 Asp Leu Pro Glu Gln Ala His Ser Ile Ile Lys Glu Cys Lys Val Val 305 310 315 320 Glu Arg Cys His Trp Gly Ile Leu Thr Asp Leu Leu His Lys Trp Asn 325 330 335 Gln Ser <210> SEQ ID NO 54 <211> LENGTH: 281 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 54 Met Ala Met Met Glu Val Gln Gly Gly Pro Ser Leu Gly Gln Thr Cys 1 5 10 15 Val Leu Ile Val Ile Phe Thr Val Leu Leu Gln Ser Leu Cys Val Ala 20 25 30 Val Thr Tyr Val Tyr Phe Thr Asn Glu Leu Lys Gln Met Gln Asp Lys 35 40 45 Tyr Ser Lys Ser Gly Ile Ala Cys Phe Leu Lys Glu Asp Asp Ser Tyr 50 55 60 Trp Asp Pro Asn Asp Glu Glu Ser Met Asn Ser Pro Cys Trp Gln Val 65 70 75 80 Lys Trp Gln Leu Arg Gln Leu Val Arg Lys Met Ile Leu Arg Thr Ser 85 90 95 Glu Glu Thr Ile Ser Thr Val Gln Glu Lys Gln Gln Asn Ile Ser Pro 100 105 110 Leu Val Arg Glu Arg Gly Pro Gln Arg Val Ala Ala His Ile Thr Gly 115 120 125 Thr Arg Gly Arg Ser Asn Thr Leu Ser Ser Pro Asn Ser Lys Asn Glu 130 135 140 Lys Ala Leu Gly Arg Lys Ile Asn Ser Trp Glu Ser Ser Arg Ser Gly 145 150 155 160 His Ser Phe Leu Ser Asn Leu His Leu Arg Asn Gly Glu Leu Val Ile 165 170 175

His Glu Lys Gly Phe Tyr Tyr Ile Tyr Ser Gln Thr Tyr Phe Arg Phe 180 185 190 Gln Glu Glu Ile Lys Glu Asn Thr Lys Asn Asp Lys Gln Met Val Gln 195 200 205 Tyr Ile Tyr Lys Tyr Thr Ser Tyr Pro Asp Pro Ile Leu Leu Met Lys 210 215 220 Ser Ala Arg Asn Ser Cys Trp Ser Lys Asp Ala Glu Tyr Gly Leu Tyr 225 230 235 240 Ser Ile Tyr Gln Gly Gly Ile Phe Glu Leu Lys Glu Asn Asp Arg Ile 245 250 255 Phe Val Ser Val Thr Asn Glu His Leu Ile Asp Met Asp His Glu Ala 260 265 270 Ser Phe Phe Gly Ala Phe Leu Val Gly 275 280 <210> SEQ ID NO 55 <211> LENGTH: 277 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 55 Met Glu Asn Thr Glu Asn Ser Val Asp Ser Lys Ser Ile Lys Asn Leu 1 5 10 15 Glu Pro Lys Ile Ile His Gly Ser Glu Ser Met Asp Ser Gly Ile Ser 20 25 30 Leu Asp Asn Ser Tyr Lys Met Asp Tyr Pro Glu Met Gly Leu Cys Ile 35 40 45 Ile Ile Asn Asn Lys Asn Phe His Lys Ser Thr Gly Met Thr Ser Arg 50 55 60 Ser Gly Thr Asp Val Asp Ala Ala Asn Leu Arg Glu Thr Phe Arg Asn 65 70 75 80 Leu Lys Tyr Glu Val Arg Asn Lys Asn Asp Leu Thr Arg Glu Glu Ile 85 90 95 Val Glu Leu Met Arg Asp Val Ser Lys Glu Asp His Ser Lys Arg Ser 100 105 110 Ser Phe Val Cys Val Leu Leu Ser His Gly Glu Glu Gly Ile Ile Phe 115 120 125 Gly Thr Asn Gly Pro Val Asp Leu Lys Lys Ile Thr Asn Phe Phe Arg 130 135 140 Gly Asp Arg Cys Arg Ser Leu Thr Gly Lys Pro Lys Leu Phe Ile Ile 145 150 155 160 Gln Ala Cys Arg Gly Thr Glu Leu Asp Cys Gly Ile Glu Thr Asp Ser 165 170 175 Gly Val Asp Asp Asp Met Ala Cys His Lys Ile Pro Val Glu Ala Asp 180 185 190 Phe Leu Tyr Ala Tyr Ser Thr Ala Pro Gly Tyr Tyr Ser Trp Arg Asn 195 200 205 Ser Lys Asp Gly Ser Trp Phe Ile Gln Ser Leu Cys Ala Met Leu Lys 210 215 220 Gln Tyr Ala Asp Lys Leu Glu Phe Met His Ile Leu Thr Arg Val Asn 225 230 235 240 Arg Lys Val Ala Thr Glu Phe Glu Ser Phe Ser Phe Asp Ala Thr Phe 245 250 255 His Ala Lys Lys Gln Ile Pro Cys Ile Val Ser Met Leu Thr Lys Glu 260 265 270 Leu Tyr Phe Tyr His 275 <210> SEQ ID NO 56 <211> LENGTH: 192 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 56 Met Asp Gly Ser Gly Glu Gln Pro Arg Gly Gly Gly Pro Thr Ser Ser 1 5 10 15 Glu Gln Ile Met Lys Thr Gly Ala Leu Leu Leu Gln Gly Phe Ile Gln 20 25 30 Asp Arg Ala Gly Arg Met Gly Gly Glu Ala Pro Glu Leu Ala Leu Asp 35 40 45 Pro Val Pro Gln Asp Ala Ser Thr Lys Lys Leu Ser Glu Cys Leu Lys 50 55 60 Arg Ile Gly Asp Glu Leu Asp Ser Asn Met Glu Leu Gln Arg Met Ile 65 70 75 80 Ala Ala Val Asp Thr Asp Ser Pro Arg Glu Val Phe Phe Arg Val Ala 85 90 95 Ala Asp Met Phe Ser Asp Gly Asn Phe Asn Trp Gly Arg Val Val Ala 100 105 110 Leu Phe Tyr Phe Ala Ser Lys Leu Val Leu Lys Ala Leu Cys Thr Lys 115 120 125 Val Pro Glu Leu Ile Arg Thr Ile Met Gly Trp Thr Leu Asp Phe Leu 130 135 140 Arg Glu Arg Leu Leu Gly Trp Ile Gln Asp Gln Gly Gly Trp Asp Gly 145 150 155 160 Leu Leu Ser Tyr Phe Gly Thr Pro Thr Trp Gln Thr Val Thr Ile Phe 165 170 175 Val Ala Gly Val Leu Thr Ala Ser Leu Thr Ile Trp Lys Lys Met Gly 180 185 190 <210> SEQ ID NO 57 <211> LENGTH: 168 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 57 Met Phe Gln Ile Pro Glu Phe Glu Pro Ser Glu Gln Glu Asp Ser Ser 1 5 10 15 Ser Ala Glu Arg Gly Leu Gly Pro Ser Pro Ala Gly Asp Gly Pro Ser 20 25 30 Gly Ser Gly Lys His His Arg Gln Ala Pro Gly Leu Leu Trp Asp Ala 35 40 45 Ser His Gln Gln Glu Gln Pro Thr Ser Ser Ser His His Gly Gly Ala 50 55 60 Gly Ala Val Glu Ile Arg Ser Arg His Ser Ser Tyr Pro Ala Gly Thr 65 70 75 80 Glu Asp Asp Glu Gly Met Gly Glu Glu Pro Ser Pro Phe Arg Gly Arg 85 90 95 Ser Arg Ser Ala Pro Pro Asn Leu Trp Ala Ala Gln Arg Tyr Gly Arg 100 105 110 Glu Leu Arg Arg Met Ser Asp Glu Phe Val Asp Ser Phe Lys Lys Gly 115 120 125 Leu Pro Arg Pro Lys Ser Ala Gly Thr Ala Thr Gln Met Arg Gln Ser 130 135 140 Ser Ser Trp Thr Arg Val Phe Gln Ser Trp Trp Asp Arg Asn Leu Gly 145 150 155 160 Arg Gly Ser Ser Ala Pro Ser Gln 165 <210> SEQ ID NO 58 <211> LENGTH: 208 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 58 Met Asp Pro Phe Leu Val Leu Leu His Ser Val Ser Ser Ser Leu Ser 1 5 10 15 Ser Ser Glu Leu Thr Glu Leu Lys Phe Leu Cys Leu Gly Arg Val Gly 20 25 30 Lys Arg Lys Leu Glu Arg Val Gln Ser Gly Leu Asp Leu Phe Ser Met 35 40 45 Leu Leu Glu Gln Asn Asp Leu Glu Pro Gly His Thr Glu Leu Leu Arg 50 55 60 Glu Leu Leu Ala Ser Leu Arg Arg His Asp Leu Leu Arg Arg Val Asp 65 70 75 80 Asp Phe Glu Ala Gly Ala Ala Ala Gly Ala Ala Pro Gly Glu Glu Asp 85 90 95 Leu Cys Ala Ala Phe Asn Val Ile Cys Asp Asn Val Gly Lys Asp Trp 100 105 110 Arg Arg Leu Ala Arg Gln Leu Lys Val Ser Asp Thr Lys Ile Asp Ser 115 120 125 Ile Glu Asp Arg Tyr Pro Arg Asn Leu Thr Glu Arg Val Arg Glu Ser 130 135 140 Leu Arg Ile Trp Lys Asn Thr Glu Lys Glu Asn Ala Thr Val Ala His 145 150 155 160 Leu Val Gly Ala Leu Arg Ser Cys Gln Met Asn Leu Val Ala Asp Leu 165 170 175 Val Gln Glu Val Gln Gln Ala Arg Asp Leu Gln Asn Arg Ser Gly Ala 180 185 190 Met Ser Pro Met Ser Trp Asn Ser Asp Ala Ser Thr Ser Glu Ala Ser 195 200 205 <210> SEQ ID NO 59 <211> LENGTH: 384 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 59 Met Ser Arg Ser Lys Arg Asp Asn Asn Phe Tyr Ser Val Glu Ile Gly 1 5 10 15 Asp Ser Thr Phe Thr Val Leu Lys Arg Tyr Gln Asn Leu Lys Pro Ile 20 25 30 Gly Ser Gly Ala Gln Gly Ile Val Cys Ala Ala Tyr Asp Ala Ile Leu 35 40 45 Glu Arg Asn Val Ala Ile Lys Lys Leu Ser Arg Pro Phe Gln Asn Gln 50 55 60 Thr His Ala Lys Arg Ala Tyr Arg Glu Leu Val Leu Met Lys Cys Val 65 70 75 80 Asn His Lys Asn Ile Ile Gly Leu Leu Asn Val Phe Thr Pro Gln Lys 85 90 95 Ser Leu Glu Glu Phe Gln Asp Val Tyr Ile Val Met Glu Leu Met Asp 100 105 110 Ala Asn Leu Cys Gln Val Ile Gln Met Glu Leu Asp His Glu Arg Met 115 120 125 Ser Tyr Leu Leu Tyr Gln Met Leu Cys Gly Ile Lys His Leu His Ser 130 135 140 Ala Gly Ile Ile His Arg Asp Leu Lys Pro Ser Asn Ile Val Val Lys

145 150 155 160 Ser Asp Cys Thr Leu Lys Ile Leu Asp Phe Gly Leu Ala Arg Thr Ala 165 170 175 Gly Thr Ser Phe Met Met Thr Pro Tyr Val Val Thr Arg Tyr Tyr Arg 180 185 190 Ala Pro Glu Val Ile Leu Gly Met Gly Tyr Lys Glu Asn Val Asp Leu 195 200 205 Trp Ser Val Gly Cys Ile Met Gly Glu Met Val Cys His Lys Ile Leu 210 215 220 Phe Pro Gly Arg Asp Tyr Ile Asp Gln Trp Asn Lys Val Ile Glu Gln 225 230 235 240 Leu Gly Thr Pro Cys Pro Glu Phe Met Lys Lys Leu Gln Pro Thr Val 245 250 255 Arg Thr Tyr Val Glu Asn Arg Pro Lys Tyr Ala Gly Tyr Ser Phe Glu 260 265 270 Lys Leu Phe Pro Asp Val Leu Phe Pro Ala Asp Ser Glu His Asn Lys 275 280 285 Leu Lys Ala Ser Gln Ala Arg Asp Leu Leu Ser Lys Met Leu Val Ile 290 295 300 Asp Ala Ser Lys Arg Ile Ser Val Asp Glu Ala Leu Gln His Pro Tyr 305 310 315 320 Ile Asn Val Trp Tyr Asp Pro Ser Glu Ala Glu Ala Pro Pro Pro Lys 325 330 335 Ile Pro Asp Lys Gln Leu Asp Glu Arg Glu His Thr Ile Glu Glu Trp 340 345 350 Lys Glu Leu Ile Tyr Lys Glu Val Met Asp Leu Glu Glu Arg Thr Lys 355 360 365 Asn Gly Val Ile Arg Gly Gln Pro Ser Pro Leu Ala Gln Val Gln Gln 370 375 380 <210> SEQ ID NO 60 <211> LENGTH: 427 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 60 Met Ser Arg Ser Lys Arg Asp Asn Asn Phe Tyr Ser Val Glu Ile Gly 1 5 10 15 Asp Ser Thr Phe Thr Val Leu Lys Arg Tyr Gln Asn Leu Lys Pro Ile 20 25 30 Gly Ser Gly Ala Gln Gly Ile Val Cys Ala Ala Tyr Asp Ala Ile Leu 35 40 45 Glu Arg Asn Val Ala Ile Lys Lys Leu Ser Arg Pro Phe Gln Asn Gln 50 55 60 Thr His Ala Lys Arg Ala Tyr Arg Glu Leu Val Leu Met Lys Cys Val 65 70 75 80 Asn His Lys Asn Ile Ile Gly Leu Leu Asn Val Phe Thr Pro Gln Lys 85 90 95 Ser Leu Glu Glu Phe Gln Asp Val Tyr Ile Val Met Glu Leu Met Asp 100 105 110 Ala Asn Leu Cys Gln Val Ile Gln Met Glu Leu Asp His Glu Arg Met 115 120 125 Ser Tyr Leu Leu Tyr Gln Met Leu Cys Gly Ile Lys His Leu His Ser 130 135 140 Ala Gly Ile Ile His Arg Asp Leu Lys Pro Ser Asn Ile Val Val Lys 145 150 155 160 Ser Asp Cys Thr Leu Lys Ile Leu Asp Phe Gly Leu Ala Arg Thr Ala 165 170 175 Gly Thr Ser Phe Met Met Thr Pro Tyr Val Val Thr Arg Tyr Tyr Arg 180 185 190 Ala Pro Glu Val Ile Leu Gly Met Gly Tyr Lys Glu Asn Val Asp Leu 195 200 205 Trp Ser Val Gly Cys Ile Met Gly Glu Met Val Cys His Lys Ile Leu 210 215 220 Phe Pro Gly Arg Asp Tyr Ile Asp Gln Trp Asn Lys Val Ile Glu Gln 225 230 235 240 Leu Gly Thr Pro Cys Pro Glu Phe Met Lys Lys Leu Gln Pro Thr Val 245 250 255 Arg Thr Tyr Val Glu Asn Arg Pro Lys Tyr Ala Gly Tyr Ser Phe Glu 260 265 270 Lys Leu Phe Pro Asp Val Leu Phe Pro Ala Asp Ser Glu His Asn Lys 275 280 285 Leu Lys Ala Ser Gln Ala Arg Asp Leu Leu Ser Lys Met Leu Val Ile 290 295 300 Asp Ala Ser Lys Arg Ile Ser Val Asp Glu Ala Leu Gln His Pro Tyr 305 310 315 320 Ile Asn Val Trp Tyr Asp Pro Ser Glu Ala Glu Ala Pro Pro Pro Lys 325 330 335 Ile Pro Asp Lys Gln Leu Asp Glu Arg Glu His Thr Ile Glu Glu Trp 340 345 350 Lys Glu Leu Ile Tyr Lys Glu Val Met Asp Leu Glu Glu Arg Thr Lys 355 360 365 Asn Gly Val Ile Arg Gly Gln Pro Ser Pro Leu Gly Ala Ala Val Ile 370 375 380 Asn Gly Ser Gln His Pro Ser Ser Ser Ser Ser Val Asn Asp Val Ser 385 390 395 400 Ser Met Ser Thr Asp Pro Thr Leu Ala Ser Asp Thr Asp Ser Ser Leu 405 410 415 Glu Ala Ala Ala Gly Pro Leu Gly Cys Cys Arg 420 425 <210> SEQ ID NO 61 <211> LENGTH: 384 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 61 Met Ser Arg Ser Lys Arg Asp Asn Asn Phe Tyr Ser Val Glu Ile Gly 1 5 10 15 Asp Ser Thr Phe Thr Val Leu Lys Arg Tyr Gln Asn Leu Lys Pro Ile 20 25 30 Gly Ser Gly Ala Gln Gly Ile Val Cys Ala Ala Tyr Asp Ala Ile Leu 35 40 45 Glu Arg Asn Val Ala Ile Lys Lys Leu Ser Arg Pro Phe Gln Asn Gln 50 55 60 Thr His Ala Lys Arg Ala Tyr Arg Glu Leu Val Leu Met Lys Cys Val 65 70 75 80 Asn His Lys Asn Ile Ile Gly Leu Leu Asn Val Phe Thr Pro Gln Lys 85 90 95 Ser Leu Glu Glu Phe Gln Asp Val Tyr Ile Val Met Glu Leu Met Asp 100 105 110 Ala Asn Leu Cys Gln Val Ile Gln Met Glu Leu Asp His Glu Arg Met 115 120 125 Ser Tyr Leu Leu Tyr Gln Met Leu Cys Gly Ile Lys His Leu His Ser 130 135 140 Ala Gly Ile Ile His Arg Asp Leu Lys Pro Ser Asn Ile Val Val Lys 145 150 155 160 Ser Asp Cys Thr Leu Lys Ile Leu Asp Phe Gly Leu Ala Arg Thr Ala 165 170 175 Gly Thr Ser Phe Met Met Thr Pro Tyr Val Val Thr Arg Tyr Tyr Arg 180 185 190 Ala Pro Glu Val Ile Leu Gly Met Gly Tyr Lys Glu Asn Val Asp Ile 195 200 205 Trp Ser Val Gly Cys Ile Met Gly Glu Met Ile Lys Gly Gly Val Leu 210 215 220 Phe Pro Gly Thr Asp His Ile Asp Gln Trp Asn Lys Val Ile Glu Gln 225 230 235 240 Leu Gly Thr Pro Cys Pro Glu Phe Met Lys Lys Leu Gln Pro Thr Val 245 250 255 Arg Thr Tyr Val Glu Asn Arg Pro Lys Tyr Ala Gly Tyr Ser Phe Glu 260 265 270 Lys Leu Phe Pro Asp Val Leu Phe Pro Ala Asp Ser Glu His Asn Lys 275 280 285 Leu Lys Ala Ser Gln Ala Arg Asp Leu Leu Ser Lys Met Leu Val Ile 290 295 300 Asp Ala Ser Lys Arg Ile Ser Val Asp Glu Ala Leu Gln His Pro Tyr 305 310 315 320 Ile Asn Val Trp Tyr Asp Pro Ser Glu Ala Glu Ala Pro Pro Pro Lys 325 330 335 Ile Pro Asp Lys Gln Leu Asp Glu Arg Glu His Thr Ile Glu Glu Trp 340 345 350 Lys Glu Leu Ile Tyr Lys Glu Val Met Asp Leu Glu Glu Arg Thr Lys 355 360 365 Asn Gly Val Ile Arg Gly Gln Pro Ser Pro Leu Ala Gln Val Gln Gln 370 375 380 <210> SEQ ID NO 62 <211> LENGTH: 427 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 62 Met Ser Arg Ser Lys Arg Asp Asn Asn Phe Tyr Ser Val Glu Ile Gly 1 5 10 15 Asp Ser Thr Phe Thr Val Leu Lys Arg Tyr Gln Asn Leu Lys Pro Ile 20 25 30 Gly Ser Gly Ala Gln Gly Ile Val Cys Ala Ala Tyr Asp Ala Ile Leu 35 40 45 Glu Arg Asn Val Ala Ile Lys Lys Leu Ser Arg Pro Phe Gln Asn Gln 50 55 60 Thr His Ala Lys Arg Ala Tyr Arg Glu Leu Val Leu Met Lys Cys Val 65 70 75 80 Asn His Lys Asn Ile Ile Gly Leu Leu Asn Val Phe Thr Pro Gln Lys 85 90 95 Ser Leu Glu Glu Phe Gln Asp Val Tyr Ile Val Met Glu Leu Met Asp 100 105 110 Ala Asn Leu Cys Gln Val Ile Gln Met Glu Leu Asp His Glu Arg Met 115 120 125 Ser Tyr Leu Leu Tyr Gln Met Leu Cys Gly Ile Lys His Leu His Ser 130 135 140 Ala Gly Ile Ile His Arg Asp Leu Lys Pro Ser Asn Ile Val Val Lys 145 150 155 160

Ser Asp Cys Thr Leu Lys Ile Leu Asp Phe Gly Leu Ala Arg Thr Ala 165 170 175 Gly Thr Ser Phe Met Met Thr Pro Tyr Val Val Thr Arg Tyr Tyr Arg 180 185 190 Ala Pro Glu Val Ile Leu Gly Met Gly Tyr Lys Glu Asn Val Asp Ile 195 200 205 Trp Ser Val Gly Cys Ile Met Gly Glu Met Ile Lys Gly Gly Val Leu 210 215 220 Phe Pro Gly Thr Asp His Ile Asp Gln Trp Asn Lys Val Ile Glu Gln 225 230 235 240 Leu Gly Thr Pro Cys Pro Glu Phe Met Lys Lys Leu Gln Pro Thr Val 245 250 255 Arg Thr Tyr Val Glu Asn Arg Pro Lys Tyr Ala Gly Tyr Ser Phe Glu 260 265 270 Lys Leu Phe Pro Asp Val Leu Phe Pro Ala Asp Ser Glu His Asn Lys 275 280 285 Leu Lys Ala Ser Gln Ala Arg Asp Leu Leu Ser Lys Met Leu Val Ile 290 295 300 Asp Ala Ser Lys Arg Ile Ser Val Asp Glu Ala Leu Gln His Pro Tyr 305 310 315 320 Ile Asn Val Trp Tyr Asp Pro Ser Glu Ala Glu Ala Pro Pro Pro Lys 325 330 335 Ile Pro Asp Lys Gln Leu Asp Glu Arg Glu His Thr Ile Glu Glu Trp 340 345 350 Lys Glu Leu Ile Tyr Lys Glu Val Met Asp Leu Glu Glu Arg Thr Lys 355 360 365 Asn Gly Val Ile Arg Gly Gln Pro Ser Pro Leu Gly Ala Ala Val Ile 370 375 380 Asn Gly Ser Gln His Pro Ser Ser Ser Ser Ser Val Asn Asp Val Ser 385 390 395 400 Ser Met Ser Thr Asp Pro Thr Leu Ala Ser Asp Thr Asp Ser Ser Leu 405 410 415 Glu Ala Ala Ala Gly Pro Leu Gly Cys Cys Arg 420 425 <210> SEQ ID NO 63 <211> LENGTH: 360 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 63 Met Ser Gln Glu Arg Pro Thr Phe Tyr Arg Gln Glu Leu Asn Lys Thr 1 5 10 15 Ile Trp Glu Val Pro Glu Arg Tyr Gln Asn Leu Ser Pro Val Gly Ser 20 25 30 Gly Ala Tyr Gly Ser Val Cys Ala Ala Phe Asp Thr Lys Thr Gly Leu 35 40 45 Arg Val Ala Val Lys Lys Leu Ser Arg Pro Phe Gln Ser Ile Ile His 50 55 60 Ala Lys Arg Thr Tyr Arg Glu Leu Arg Leu Leu Lys His Met Lys His 65 70 75 80 Glu Asn Val Ile Gly Leu Leu Asp Val Phe Thr Pro Ala Arg Ser Leu 85 90 95 Glu Glu Phe Asn Asp Val Tyr Leu Val Thr His Leu Met Gly Ala Asp 100 105 110 Leu Asn Asn Ile Val Lys Cys Gln Lys Leu Thr Asp Asp His Val Gln 115 120 125 Phe Leu Ile Tyr Gln Ile Leu Arg Gly Leu Lys Tyr Ile His Ser Ala 130 135 140 Asp Ile Ile His Arg Asp Leu Lys Pro Ser Asn Leu Ala Val Asn Glu 145 150 155 160 Asp Cys Glu Leu Lys Ile Leu Asp Phe Gly Leu Ala Arg His Thr Asp 165 170 175 Asp Glu Met Thr Gly Tyr Val Ala Thr Arg Trp Tyr Arg Ala Pro Glu 180 185 190 Ile Met Leu Asn Trp Met His Tyr Asn Gln Thr Val Asp Ile Trp Ser 195 200 205 Val Gly Cys Ile Met Ala Glu Leu Leu Thr Gly Arg Thr Leu Phe Pro 210 215 220 Gly Thr Asp His Ile Asn Gln Leu Gln Gln Ile Met Arg Leu Thr Gly 225 230 235 240 Thr Pro Pro Ala Tyr Leu Ile Asn Arg Met Pro Ser His Glu Ala Arg 245 250 255 Asn Tyr Ile Gln Ser Leu Thr Gln Met Pro Lys Met Asn Phe Ala Asn 260 265 270 Val Phe Ile Gly Ala Asn Pro Leu Ala Val Asp Leu Leu Glu Lys Met 275 280 285 Leu Val Leu Asp Ser Asp Lys Arg Ile Thr Ala Ala Gln Ala Leu Ala 290 295 300 His Ala Tyr Phe Ala Gln Tyr His Asp Pro Asp Asp Glu Pro Val Ala 305 310 315 320 Asp Pro Tyr Asp Gln Ser Phe Glu Ser Arg Asp Leu Leu Ile Asp Glu 325 330 335 Trp Lys Ser Leu Thr Tyr Asp Glu Val Ile Ser Phe Val Pro Pro Pro 340 345 350 Leu Asp Gln Glu Glu Met Glu Ser 355 360 <210> SEQ ID NO 64 <211> LENGTH: 240 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 64 Met Glu Asp Tyr Thr Lys Ile Glu Lys Ile Gly Glu Gly Thr Tyr Gly 1 5 10 15 Val Val Tyr Lys Gly Arg His Lys Thr Thr Gly Gln Val Val Ala Met 20 25 30 Lys Lys Ile Arg Leu Glu Ser Glu Glu Glu Gly Val Pro Ser Thr Ala 35 40 45 Ile Arg Glu Ile Ser Leu Leu Lys Glu Leu Arg His Pro Asn Ile Val 50 55 60 Ser Leu Gln Asp Val Leu Met Gln Asp Ser Arg Leu Tyr Leu Ile Phe 65 70 75 80 Glu Phe Leu Ser Met Asp Leu Lys Lys Tyr Leu Asp Ser Ile Pro Pro 85 90 95 Gly Gln Tyr Met Asp Ser Ser Leu Val Lys Val Val Thr Leu Trp Tyr 100 105 110 Arg Ser Pro Glu Val Leu Leu Gly Ser Ala Arg Tyr Ser Thr Pro Val 115 120 125 Asp Ile Trp Ser Ile Gly Thr Ile Phe Ala Glu Leu Ala Thr Lys Lys 130 135 140 Pro Leu Phe His Gly Asp Ser Glu Ile Asp Gln Leu Phe Arg Ile Phe 145 150 155 160 Arg Ala Leu Gly Thr Pro Asn Asn Glu Val Trp Pro Glu Val Glu Ser 165 170 175 Leu Gln Asp Tyr Lys Asn Thr Phe Pro Lys Trp Lys Pro Gly Ser Leu 180 185 190 Ala Ser His Val Lys Asn Leu Asp Glu Asn Gly Leu Asp Leu Leu Ser 195 200 205 Lys Met Leu Ile Tyr Asp Pro Ala Lys Arg Ile Ser Gly Lys Met Ala 210 215 220 Leu Asn His Pro Tyr Phe Asn Asp Leu Asp Asn Gln Ile Lys Lys Met 225 230 235 240 <210> SEQ ID NO 65 <211> LENGTH: 432 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 65 Met Leu Gly Asn Ser Ala Pro Gly Pro Ala Thr Arg Glu Ala Gly Ser 1 5 10 15 Ala Leu Leu Ala Leu Gln Gln Thr Ala Leu Gln Glu Asp Gln Glu Asn 20 25 30 Ile Asn Pro Glu Lys Ala Ala Pro Val Gln Gln Pro Arg Thr Arg Ala 35 40 45 Ala Leu Ala Val Leu Lys Ser Gly Asn Pro Arg Gly Leu Ala Gln Gln 50 55 60 Gln Arg Pro Lys Thr Arg Arg Val Ala Pro Leu Lys Asp Leu Pro Val 65 70 75 80 Asn Asp Glu His Val Thr Val Pro Pro Trp Lys Ala Asn Ser Lys Gln 85 90 95 Pro Ala Phe Thr Ile His Val Asp Glu Ala Glu Lys Glu Ala Gln Lys 100 105 110 Lys Pro Ala Glu Ser Gln Lys Ile Glu Arg Glu Asp Ala Leu Ala Phe 115 120 125 Asn Ser Ala Ile Ser Leu Pro Gly Pro Arg Lys Pro Leu Val Pro Leu 130 135 140 Asp Tyr Pro Met Asp Gly Ser Phe Glu Ser Pro His Thr Met Asp Met 145 150 155 160 Ser Ile Val Leu Glu Asp Glu Lys Pro Val Ser Val Asn Glu Val Pro 165 170 175 Asp Tyr His Glu Asp Ile His Thr Tyr Leu Arg Glu Met Glu Val Lys 180 185 190 Cys Lys Pro Lys Val Gly Tyr Met Lys Lys Gln Pro Asp Ile Thr Asn 195 200 205 Ser Met Arg Ala Ile Leu Val Asp Trp Leu Val Glu Val Gly Glu Glu 210 215 220 Tyr Lys Leu Gln Asn Glu Thr Leu His Leu Ala Val Asn Tyr Ile Asp 225 230 235 240 Arg Phe Leu Ser Ser Met Ser Val Leu Arg Gly Lys Leu Gln Leu Val 245 250 255 Gly Thr Ala Ala Met Leu Leu Ala Ser Lys Phe Glu Glu Ile Tyr Pro 260 265 270 Pro Glu Val Ala Glu Phe Val Tyr Ile Thr Asp Asp Thr Tyr Thr Lys 275 280 285 Lys Gln Val Leu Arg Met Glu His Leu Val Leu Lys Val Leu Thr Phe 290 295 300 Asp Leu Ala Ala Pro Thr Val Asn Gln Phe Leu Thr Gln Tyr Phe Leu 305 310 315 320 His Gln Gln Pro Ala Asn Cys Lys Val Glu Ser Leu Ala Met Phe Leu 325 330 335

Gly Glu Leu Ser Leu Ile Asp Ala Asp Pro Tyr Leu Lys Tyr Leu Pro 340 345 350 Ser Val Ile Ala Gly Ala Ala Phe His Leu Ala Leu Tyr Thr Val Thr 355 360 365 Gly Gln Ser Trp Pro Glu Ser Leu Ile Arg Lys Thr Gly Tyr Thr Leu 370 375 380 Glu Ser Leu Lys Pro Cys Leu Met Asp Leu His Gln Thr Tyr Leu Lys 385 390 395 400 Ala Pro Gln His Ala Gln Gln Ser Ile Arg Glu Lys Tyr Lys Asn Ser 405 410 415 Lys Tyr His Gly Val Ser Leu Leu Asn Pro Pro Glu Thr Leu Asn Leu 420 425 430 <210> SEQ ID NO 66 <211> LENGTH: 289 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 66 Met Glu Leu Leu Cys His Glu Val Asp Pro Val Arg Arg Ala Val Arg 1 5 10 15 Asp Arg Asn Leu Leu Arg Asp Asp Arg Val Leu Gln Asn Leu Leu Thr 20 25 30 Ile Glu Glu Arg Tyr Leu Pro Gln Cys Ser Tyr Phe Lys Cys Val Gln 35 40 45 Lys Asp Ile Gln Pro Tyr Met Arg Arg Met Val Ala Thr Trp Met Leu 50 55 60 Glu Val Cys Glu Glu Gln Lys Cys Glu Glu Glu Val Phe Pro Leu Ala 65 70 75 80 Met Asn Tyr Leu Asp Arg Phe Leu Ala Gly Val Pro Thr Pro Lys Ser 85 90 95 His Leu Gln Leu Leu Gly Ala Val Cys Met Phe Leu Ala Ser Lys Leu 100 105 110 Lys Glu Thr Ser Pro Leu Thr Ala Glu Lys Leu Cys Ile Tyr Thr Asp 115 120 125 Asn Ser Ile Lys Pro Gln Glu Leu Leu Glu Trp Glu Leu Val Val Leu 130 135 140 Gly Lys Leu Lys Trp Asn Leu Ala Ala Val Thr Pro His Asp Phe Ile 145 150 155 160 Glu His Ile Leu Arg Lys Leu Pro Gln Gln Arg Glu Lys Leu Ser Leu 165 170 175 Ile Arg Lys His Ala Gln Thr Phe Ile Ala Leu Cys Ala Thr Asp Phe 180 185 190 Lys Phe Ala Met Tyr Pro Pro Ser Met Ile Ala Thr Gly Ser Val Gly 195 200 205 Ala Ala Ile Cys Gly Leu Gln Gln Asp Glu Glu Val Ser Ser Leu Thr 210 215 220 Cys Asp Ala Leu Thr Glu Leu Leu Ala Lys Ile Thr Asn Thr Asp Val 225 230 235 240 Asp Cys Leu Lys Ala Cys Gln Glu Gln Ile Glu Ala Val Leu Leu Asn 245 250 255 Ser Leu Gln Gln Tyr Arg Gln Asp Gln Arg Asp Gly Ser Lys Ser Glu 260 265 270 Asp Glu Leu Asp Gln Ala Ser Thr Pro Thr Asp Val Arg Asp Ile Asp 275 280 285 Leu <210> SEQ ID NO 67 <211> LENGTH: 292 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 67 Met Glu Leu Leu Cys Cys Glu Gly Thr Arg His Ala Pro Arg Ala Gly 1 5 10 15 Pro Asp Pro Arg Leu Leu Gly Asp Gln Arg Val Leu Gln Ser Leu Leu 20 25 30 Arg Leu Glu Glu Arg Tyr Val Pro Arg Ala Ser Tyr Phe Gln Cys Val 35 40 45 Gln Arg Glu Ile Lys Pro His Met Arg Lys Met Leu Ala Tyr Trp Met 50 55 60 Leu Glu Val Cys Glu Glu Gln Arg Cys Glu Glu Glu Val Phe Pro Leu 65 70 75 80 Ala Met Asn Tyr Leu Asp Arg Tyr Leu Ser Cys Val Pro Thr Arg Lys 85 90 95 Ala Gln Leu Gln Leu Leu Gly Ala Val Cys Met Leu Leu Ala Ser Lys 100 105 110 Leu Arg Glu Thr Thr Pro Leu Thr Ile Glu Lys Leu Cys Ile Tyr Thr 115 120 125 Asp His Ala Val Ser Pro Arg Gln Leu Arg Asp Trp Glu Val Leu Val 130 135 140 Leu Gly Lys Leu Lys Trp Asp Leu Ala Ala Val Ile Ala His Asp Phe 145 150 155 160 Leu Ala Phe Ile Leu His Arg Leu Ser Leu Pro Arg Asp Arg Gln Ala 165 170 175 Leu Val Lys Lys His Ala Gln Thr Phe Leu Ala Leu Cys Ala Thr Asp 180 185 190 Tyr Thr Phe Ala Met Tyr Pro Pro Ser Met Ile Ala Thr Gly Ser Ile 195 200 205 Gly Ala Ala Val Gln Gly Leu Gly Ala Cys Ser Met Ser Gly Asp Glu 210 215 220 Leu Thr Glu Leu Leu Ala Gly Ile Thr Gly Thr Glu Val Asp Cys Leu 225 230 235 240 Arg Ala Cys Gln Glu Gln Ile Glu Ala Ala Leu Arg Glu Ser Leu Arg 245 250 255 Glu Ala Ser Gln Thr Ser Ser Ser Pro Ala Pro Lys Ala Pro Arg Gly 260 265 270 Ser Ser Ser Gln Gly Pro Ser Gln Thr Ser Thr Pro Thr Asp Val Thr 275 280 285 Ala Ile His Leu 290 <210> SEQ ID NO 68 <211> LENGTH: 410 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 68 Met Pro Arg Glu Arg Arg Glu Arg Asp Ala Lys Glu Arg Asp Thr Met 1 5 10 15 Lys Glu Asp Gly Gly Ala Glu Phe Ser Ala Arg Ser Arg Lys Arg Lys 20 25 30 Ala Asn Val Thr Val Phe Leu Gln Asp Pro Asp Glu Glu Met Ala Lys 35 40 45 Ile Asp Arg Thr Ala Arg Asp Gln Cys Gly Ser Gln Pro Trp Asp Asn 50 55 60 Asn Ala Val Cys Ala Asp Pro Cys Ser Leu Ile Pro Thr Pro Asp Lys 65 70 75 80 Glu Asp Asp Asp Arg Val Tyr Pro Asn Ser Thr Cys Lys Pro Arg Ile 85 90 95 Ile Ala Pro Ser Arg Gly Ser Pro Leu Pro Val Leu Ser Trp Ala Asn 100 105 110 Arg Glu Glu Val Trp Lys Ile Met Leu Asn Lys Glu Lys Thr Tyr Leu 115 120 125 Arg Asp Gln His Phe Leu Glu Gln His Pro Leu Leu Gln Pro Lys Met 130 135 140 Arg Ala Ile Leu Leu Asp Trp Leu Met Glu Val Cys Glu Val Tyr Lys 145 150 155 160 Leu His Arg Glu Thr Phe Tyr Leu Ala Gln Asp Phe Phe Asp Arg Tyr 165 170 175 Met Ala Thr Gln Glu Asn Val Val Lys Thr Leu Leu Gln Leu Ile Gly 180 185 190 Ile Ser Ser Leu Phe Ile Ala Ala Lys Leu Glu Glu Ile Tyr Pro Pro 195 200 205 Lys Leu His Gln Phe Ala Tyr Val Thr Asp Gly Ala Cys Ser Gly Asp 210 215 220 Glu Ile Leu Thr Met Glu Leu Met Ile Met Lys Ala Leu Lys Trp Arg 225 230 235 240 Leu Ser Pro Leu Thr Ile Val Ser Trp Leu Asn Val Tyr Met Gln Val 245 250 255 Ala Tyr Leu Asn Asp Leu His Glu Val Leu Leu Pro Gln Tyr Pro Gln 260 265 270 Gln Ile Phe Ile Gln Ile Ala Glu Leu Leu Asp Leu Cys Val Leu Asp 275 280 285 Val Asp Cys Leu Glu Phe Pro Tyr Gly Ile Leu Ala Ala Ser Ala Leu 290 295 300 Tyr His Phe Ser Ser Ser Glu Leu Met Gln Lys Val Ser Gly Tyr Gln 305 310 315 320 Trp Cys Asp Ile Glu Asn Cys Val Lys Trp Met Val Pro Phe Ala Met 325 330 335 Val Ile Arg Glu Thr Gly Ser Ser Lys Leu Lys His Phe Arg Gly Val 340 345 350 Ala Asp Glu Asp Ala His Asn Ile Gln Thr His Arg Asp Ser Leu Asp 355 360 365 Leu Leu Asp Lys Ala Arg Ala Lys Lys Ala Met Leu Ser Glu Gln Asn 370 375 380 Arg Ala Ser Pro Leu Pro Ser Gly Leu Leu Thr Pro Pro Gln Ser Gly 385 390 395 400 Lys Lys Gln Ser Ser Gly Pro Glu Met Ala 405 410 <210> SEQ ID NO 69 <211> LENGTH: 473 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 69 Met Ser Thr Glu Leu Phe Ser Ser Thr Arg Glu Glu Gly Ser Ser Gly 1 5 10 15 Ser Gly Pro Ser Phe Arg Ser Asn Gln Arg Lys Met Leu Asn Leu Leu 20 25 30 Leu Glu Arg Asp Thr Ser Phe Thr Val Cys Pro Asp Val Pro Arg Thr 35 40 45 Pro Val Gly Lys Phe Leu Gly Asp Ser Ala Asn Leu Ser Ile Leu Ser

50 55 60 Gly Gly Thr Pro Lys Arg Cys Leu Asp Leu Ser Asn Leu Ser Ser Gly 65 70 75 80 Glu Ile Thr Ala Thr Gln Leu Thr Thr Ser Ala Asp Leu Asp Glu Thr 85 90 95 Gly His Leu Asp Ser Ser Gly Leu Gln Glu Val His Leu Ala Gly Met 100 105 110 Asn His Asp Gln His Leu Met Lys Cys Ser Pro Ala Gln Leu Leu Cys 115 120 125 Ser Thr Pro Asn Gly Leu Asp Arg Gly His Arg Lys Arg Asp Ala Met 130 135 140 Cys Ser Ser Ser Ala Asn Lys Glu Asn Asp Asn Gly Asn Leu Val Asp 145 150 155 160 Ser Glu Met Lys Tyr Leu Gly Ser Pro Ile Thr Thr Val Pro Lys Leu 165 170 175 Asp Lys Asn Pro Asn Leu Gly Glu Asp Gln Ala Glu Glu Ile Ser Asp 180 185 190 Glu Leu Met Glu Phe Ser Leu Lys Asp Gln Glu Ala Lys Val Ser Arg 195 200 205 Ser Gly Leu Tyr Arg Ser Pro Ser Met Pro Glu Asn Leu Asn Arg Pro 210 215 220 Arg Leu Lys Gln Val Glu Lys Phe Lys Asp Asn Thr Ile Pro Asp Lys 225 230 235 240 Val Lys Lys Lys Tyr Phe Ser Gly Gln Gly Lys Leu Arg Lys Gly Leu 245 250 255 Cys Leu Lys Lys Thr Val Ser Leu Cys Asp Ile Thr Ile Thr Gln Met 260 265 270 Leu Glu Glu Asp Ser Asn Gln Gly His Leu Ile Gly Asp Phe Ser Lys 275 280 285 Val Cys Ala Leu Pro Thr Val Ser Gly Lys His Gln Asp Leu Lys Tyr 290 295 300 Val Asn Pro Glu Thr Val Ala Ala Leu Leu Ser Gly Lys Phe Gln Gly 305 310 315 320 Leu Ile Glu Lys Phe Tyr Val Ile Asp Cys Arg Tyr Pro Tyr Glu Tyr 325 330 335 Leu Gly Gly His Ile Gln Gly Ala Leu Asn Leu Tyr Ser Gln Glu Glu 340 345 350 Leu Phe Asn Phe Phe Leu Lys Lys Pro Ile Val Pro Leu Asp Thr Gln 355 360 365 Lys Arg Ile Ile Ile Val Phe His Cys Glu Phe Ser Ser Glu Arg Gly 370 375 380 Pro Arg Met Cys Arg Cys Leu Arg Glu Glu Asp Arg Ser Leu Asn Gln 385 390 395 400 Tyr Pro Ala Leu Tyr Tyr Pro Glu Leu Tyr Ile Leu Lys Gly Gly Tyr 405 410 415 Arg Asp Phe Phe Pro Glu Tyr Met Glu Leu Cys Glu Pro Gln Ser Tyr 420 425 430 Cys Pro Met His His Gln Asp His Lys Thr Glu Leu Leu Arg Cys Arg 435 440 445 Ser Gln Ser Lys Val Gln Glu Gly Glu Arg Gln Leu Arg Glu Gln Ile 450 455 460 Ala Leu Leu Val Lys Asp Met Ser Pro 465 470 <210> SEQ ID NO 70 <211> LENGTH: 400 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 70 Met Ser Thr Glu Leu Phe Ser Ser Thr Arg Glu Glu Gly Ser Ser Gly 1 5 10 15 Ser Gly Pro Ser Phe Arg Ser Asn Gln Arg Lys Met Leu Asn Leu Leu 20 25 30 Leu Glu Arg Asp Thr Ser Phe Thr Val Cys Pro Asp Val Pro Arg Thr 35 40 45 Pro Val Gly Lys Phe Leu Gly Asp Ser Ala Asn Leu Ser Ile Leu Ser 50 55 60 Gly Ser Pro Gly Phe Phe Arg Thr Ser Gly Ser Ala Phe Ser Trp Asp 65 70 75 80 Asp Asn Gly Asn Leu Val Asp Ser Glu Met Lys Tyr Leu Gly Ser Pro 85 90 95 Ile Thr Thr Val Pro Lys Leu Asp Lys Asn Pro Asn Leu Gly Glu Asp 100 105 110 Gln Ala Glu Glu Ile Ser Asp Glu Leu Met Glu Phe Ser Leu Lys Asp 115 120 125 Gln Glu Ala Lys Val Ser Arg Ser Gly Leu Tyr Arg Ser Pro Ser Met 130 135 140 Pro Glu Asn Leu Asn Arg Pro Arg Leu Lys Gln Val Glu Lys Phe Lys 145 150 155 160 Asp Asn Thr Ile Pro Asp Lys Val Lys Lys Lys Tyr Phe Ser Gly Gln 165 170 175 Gly Lys Leu Arg Lys Gly Leu Cys Leu Lys Lys Thr Val Ser Leu Cys 180 185 190 Asp Ile Thr Ile Thr Gln Met Leu Glu Glu Asp Ser Asn Gln Gly His 195 200 205 Leu Ile Gly Asp Phe Ser Lys Val Cys Ala Leu Pro Thr Val Ser Gly 210 215 220 Lys His Gln Asp Leu Lys Tyr Val Asn Pro Glu Thr Val Ala Ala Leu 225 230 235 240 Leu Ser Gly Lys Phe Gln Gly Leu Ile Glu Lys Phe Tyr Val Ile Asp 245 250 255 Cys Arg Tyr Pro Tyr Glu Tyr Leu Gly Gly His Ile Gln Gly Ala Leu 260 265 270 Asn Leu Tyr Ser Gln Glu Glu Leu Phe Asn Phe Phe Leu Lys Lys Pro 275 280 285 Ile Val Pro Leu Asp Thr Gln Lys Arg Ile Ile Ile Val Phe His Cys 290 295 300 Glu Phe Ser Ser Glu Arg Gly Pro Arg Met Cys Arg Cys Leu Arg Glu 305 310 315 320 Glu Asp Arg Ser Leu Asn Gln Tyr Pro Ala Leu Tyr Tyr Pro Glu Leu 325 330 335 Tyr Ile Leu Lys Gly Gly Tyr Arg Asp Phe Phe Pro Glu Tyr Met Glu 340 345 350 Leu Cys Glu Pro Gln Ser Tyr Cys Pro Met His His Gln Asp His Lys 355 360 365 Thr Glu Leu Leu Arg Cys Arg Ser Gln Ser Lys Val Gln Glu Gly Glu 370 375 380 Arg Gln Leu Arg Glu Gln Ile Ala Leu Leu Val Lys Asp Met Ser Pro 385 390 395 400 <210> SEQ ID NO 71 <211> LENGTH: 164 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 71 Met Ser Glu Pro Ala Gly Asp Val Arg Gln Asn Pro Cys Gly Ser Lys 1 5 10 15 Ala Cys Arg Arg Leu Phe Gly Pro Val Asp Ser Glu Gln Leu Ser Arg 20 25 30 Asp Cys Asp Ala Leu Met Ala Gly Cys Ile Gln Glu Ala Arg Glu Arg 35 40 45 Trp Asn Phe Asp Phe Val Thr Glu Thr Pro Leu Glu Gly Asp Phe Ala 50 55 60 Trp Glu Arg Val Arg Gly Leu Gly Leu Pro Lys Leu Tyr Leu Pro Thr 65 70 75 80 Gly Pro Arg Arg Gly Arg Asp Glu Leu Gly Gly Gly Arg Arg Pro Gly 85 90 95 Thr Ser Pro Ala Leu Leu Gln Gly Thr Ala Glu Glu Asp His Val Asp 100 105 110 Leu Ser Leu Ser Cys Thr Leu Val Pro Arg Ser Gly Glu Gln Ala Glu 115 120 125 Gly Ser Pro Gly Gly Pro Gly Asp Ser Gln Gly Arg Lys Arg Arg Gln 130 135 140 Thr Ser Met Thr Asp Phe Tyr His Ser Lys Arg Arg Leu Ile Phe Ser 145 150 155 160 Lys Arg Lys Pro <210> SEQ ID NO 72 <211> LENGTH: 156 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 72 Met Glu Pro Ala Ala Gly Ser Ser Met Glu Pro Ser Ala Asp Trp Leu 1 5 10 15 Ala Thr Ala Ala Ala Arg Gly Arg Val Glu Glu Val Arg Ala Leu Leu 20 25 30 Glu Ala Gly Ala Leu Pro Asn Ala Pro Asn Ser Tyr Gly Arg Arg Pro 35 40 45 Ile Gln Val Met Met Met Gly Ser Ala Arg Val Ala Glu Leu Leu Leu 50 55 60 Leu His Gly Ala Glu Pro Asn Cys Ala Asp Pro Ala Thr Leu Thr Arg 65 70 75 80 Pro Val His Asp Ala Ala Arg Glu Gly Phe Leu Asp Thr Leu Val Val 85 90 95 Leu His Arg Ala Gly Ala Arg Leu Asp Val Arg Asp Ala Trp Gly Arg 100 105 110 Leu Pro Val Asp Leu Ala Glu Glu Leu Gly His Arg Asp Val Ala Arg 115 120 125 Tyr Leu Arg Ala Ala Ala Gly Gly Thr Arg Gly Ser Asn His Ala Arg 130 135 140 Ile Asp Ala Ala Glu Gly Pro Ser Asp Ile Pro Asp 145 150 155 <210> SEQ ID NO 73 <211> LENGTH: 116 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 73 Met Glu Pro Ala Ala Gly Ser Ser Met Glu Pro Ser Ala Asp Trp Leu 1 5 10 15

Ala Thr Ala Ala Ala Arg Gly Arg Val Glu Glu Val Arg Ala Leu Leu 20 25 30 Glu Ala Gly Ala Leu Pro Asn Ala Pro Asn Ser Tyr Gly Arg Arg Pro 35 40 45 Ile Gln Val Gly Arg Gly Ser Ala Ala Gly Ala Gly Asp Gly Gly Arg 50 55 60 Leu Trp Arg Thr Lys Phe Ala Gly Glu Leu Glu Ser Gly Ser Ala Ser 65 70 75 80 Ile Leu Arg Lys Lys Gly Arg Leu Pro Gly Glu Phe Ser Glu Gly Val 85 90 95 Cys Asn His Arg Pro Pro Pro Gly Asp Ala Leu Gly Ala Trp Glu Ala 100 105 110 Lys Glu Glu Glu 115 <210> SEQ ID NO 74 <211> LENGTH: 173 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 74 Met Gly Arg Gly Arg Cys Val Gly Pro Ser Leu Gln Leu Arg Gly Gln 1 5 10 15 Glu Trp Arg Cys Ser Pro Leu Val Pro Lys Gly Gly Ala Ala Ala Ala 20 25 30 Glu Leu Gly Pro Gly Gly Gly Glu Asn Met Val Arg Arg Phe Leu Val 35 40 45 Thr Leu Arg Ile Arg Arg Ala Cys Gly Pro Pro Arg Val Arg Val Phe 50 55 60 Val Val His Ile Pro Arg Leu Thr Gly Glu Trp Ala Ala Pro Gly Ala 65 70 75 80 Pro Ala Ala Val Ala Leu Val Leu Met Leu Leu Arg Ser Gln Arg Leu 85 90 95 Gly Gln Gln Pro Leu Pro Arg Arg Pro Gly His Asp Asp Gly Gln Arg 100 105 110 Pro Ser Gly Gly Ala Ala Ala Ala Pro Arg Arg Gly Ala Gln Leu Arg 115 120 125 Arg Pro Arg His Ser His Pro Thr Arg Ala Arg Arg Cys Pro Gly Gly 130 135 140 Leu Pro Gly His Ala Gly Gly Ala Ala Pro Gly Arg Gly Ala Ala Gly 145 150 155 160 Arg Ala Arg Cys Leu Gly Pro Ser Ala Arg Gly Pro Gly 165 170 <210> SEQ ID NO 75 <211> LENGTH: 298 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 75 Met Glu Asn Phe Gln Lys Val Glu Lys Ile Gly Glu Gly Thr Tyr Gly 1 5 10 15 Val Val Tyr Lys Ala Arg Asn Lys Leu Thr Gly Glu Val Val Ala Leu 20 25 30 Lys Lys Ile Arg Leu Asp Thr Glu Thr Glu Gly Val Pro Ser Thr Ala 35 40 45 Ile Arg Glu Ile Ser Leu Leu Lys Glu Leu Asn His Pro Asn Ile Val 50 55 60 Lys Leu Leu Asp Val Ile His Thr Glu Asn Lys Leu Tyr Leu Val Phe 65 70 75 80 Glu Phe Leu His Gln Asp Leu Lys Lys Phe Met Asp Ala Ser Ala Leu 85 90 95 Thr Gly Ile Pro Leu Pro Leu Ile Lys Ser Tyr Leu Phe Gln Leu Leu 100 105 110 Gln Gly Leu Ala Phe Cys His Ser His Arg Val Leu His Arg Asp Leu 115 120 125 Lys Pro Gln Asn Leu Leu Ile Asn Thr Glu Gly Ala Ile Lys Leu Ala 130 135 140 Asp Phe Gly Leu Ala Arg Ala Phe Gly Val Pro Val Arg Thr Tyr Thr 145 150 155 160 His Glu Val Val Thr Leu Trp Tyr Arg Ala Pro Glu Ile Leu Leu Gly 165 170 175 Cys Lys Tyr Tyr Ser Thr Ala Val Asp Ile Trp Ser Leu Gly Cys Ile 180 185 190 Phe Ala Glu Met Val Thr Arg Arg Ala Leu Phe Pro Gly Asp Ser Glu 195 200 205 Ile Asp Gln Leu Phe Arg Ile Phe Arg Thr Leu Gly Thr Pro Asp Glu 210 215 220 Val Val Trp Pro Gly Val Thr Ser Met Pro Asp Tyr Lys Pro Ser Phe 225 230 235 240 Pro Lys Trp Ala Arg Gln Asp Phe Ser Lys Val Val Pro Pro Leu Asp 245 250 255 Glu Asp Gly Arg Ser Leu Leu Ser Gln Met Leu His Tyr Asp Pro Asn 260 265 270 Lys Arg Ile Ser Ala Lys Ala Ala Leu Ala His Pro Phe Phe Gln Asp 275 280 285 Val Thr Lys Pro Val Pro His Leu Arg Leu 290 295 <210> SEQ ID NO 76 <211> LENGTH: 264 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 76 Met Glu Asn Phe Gln Lys Val Glu Lys Ile Gly Glu Gly Thr Tyr Gly 1 5 10 15 Val Val Tyr Lys Ala Arg Asn Lys Leu Thr Gly Glu Val Val Ala Leu 20 25 30 Lys Lys Ile Arg Leu Asp Thr Glu Thr Glu Gly Val Pro Ser Thr Ala 35 40 45 Ile Arg Glu Ile Ser Leu Leu Lys Glu Leu Asn His Pro Asn Ile Val 50 55 60 Lys Leu Leu Asp Val Ile His Thr Glu Asn Lys Leu Tyr Leu Val Phe 65 70 75 80 Glu Phe Leu His Gln Asp Leu Lys Lys Phe Met Asp Ala Ser Ala Leu 85 90 95 Thr Gly Ile Pro Leu Pro Leu Ile Lys Ser Tyr Leu Phe Gln Leu Leu 100 105 110 Gln Gly Leu Ala Phe Cys His Ser His Arg Val Leu His Arg Asp Leu 115 120 125 Lys Pro Gln Asn Leu Leu Ile Asn Thr Glu Gly Ala Ile Lys Leu Ala 130 135 140 Asp Phe Gly Leu Ala Arg Ala Phe Gly Val Pro Val Arg Thr Tyr Thr 145 150 155 160 His Glu Val Thr Arg Arg Ala Leu Phe Pro Gly Asp Ser Glu Ile Asp 165 170 175 Gln Leu Phe Arg Ile Phe Arg Thr Leu Gly Thr Pro Asp Glu Val Val 180 185 190 Trp Pro Gly Val Thr Ser Met Pro Asp Tyr Lys Pro Ser Phe Pro Lys 195 200 205 Trp Ala Arg Gln Asp Phe Ser Lys Val Val Pro Pro Leu Asp Glu Asp 210 215 220 Gly Arg Ser Leu Leu Ser Gln Met Leu His Tyr Asp Pro Asn Lys Arg 225 230 235 240 Ile Ser Ala Lys Ala Ala Leu Ala His Pro Phe Phe Gln Asp Val Thr 245 250 255 Lys Pro Val Pro His Leu Arg Leu 260 <210> SEQ ID NO 77 <211> LENGTH: 303 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 77 Met Ala Thr Ser Arg Tyr Glu Pro Val Ala Glu Ile Gly Val Gly Ala 1 5 10 15 Tyr Gly Thr Val Tyr Lys Ala Arg Asp Pro His Ser Gly His Phe Val 20 25 30 Ala Leu Lys Ser Val Arg Val Pro Asn Gly Gly Gly Gly Gly Gly Gly 35 40 45 Leu Pro Ile Ser Thr Val Arg Glu Val Ala Leu Leu Arg Arg Leu Glu 50 55 60 Ala Phe Glu His Pro Asn Val Val Arg Leu Met Asp Val Cys Ala Thr 65 70 75 80 Ser Arg Thr Asp Arg Glu Ile Lys Val Thr Leu Val Phe Glu His Val 85 90 95 Asp Gln Asp Leu Arg Thr Tyr Leu Asp Lys Ala Pro Pro Pro Gly Leu 100 105 110 Pro Ala Glu Thr Ile Lys Asp Leu Met Arg Gln Phe Leu Arg Gly Leu 115 120 125 Asp Phe Leu His Ala Asn Cys Ile Val His Arg Asp Leu Lys Pro Glu 130 135 140 Asn Ile Leu Val Thr Ser Gly Gly Thr Val Lys Leu Ala Asp Phe Gly 145 150 155 160 Leu Ala Arg Ile Tyr Ser Tyr Gln Met Ala Leu Thr Pro Val Val Val 165 170 175 Thr Leu Trp Tyr Arg Ala Pro Glu Val Leu Leu Gln Ser Thr Tyr Ala 180 185 190 Thr Pro Val Asp Met Trp Ser Val Gly Cys Ile Phe Ala Glu Met Phe 195 200 205 Arg Arg Lys Pro Leu Phe Cys Gly Asn Ser Glu Ala Asp Gln Leu Gly 210 215 220 Lys Ile Phe Asp Leu Ile Gly Leu Pro Pro Glu Asp Asp Trp Pro Arg 225 230 235 240 Asp Val Ser Leu Pro Arg Gly Ala Phe Pro Pro Arg Gly Pro Arg Pro 245 250 255 Val Gln Ser Val Val Pro Glu Met Glu Glu Ser Gly Ala Gln Leu Leu 260 265 270 Leu Glu Met Leu Thr Phe Asn Pro His Lys Arg Ile Ser Ala Phe Arg 275 280 285 Ala Leu Gln His Ser Tyr Leu His Lys Asp Glu Gly Asn Pro Glu 290 295 300

<210> SEQ ID NO 78 <211> LENGTH: 326 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 78 Met Glu Lys Asp Gly Leu Cys Arg Ala Asp Gln Gln Tyr Glu Cys Val 1 5 10 15 Ala Glu Ile Gly Glu Gly Ala Tyr Gly Lys Val Phe Lys Ala Arg Asp 20 25 30 Leu Lys Asn Gly Gly Arg Phe Val Ala Leu Lys Arg Val Arg Val Gln 35 40 45 Thr Gly Glu Glu Gly Met Pro Leu Ser Thr Ile Arg Glu Val Ala Val 50 55 60 Leu Arg His Leu Glu Thr Phe Glu His Pro Asn Val Val Arg Leu Phe 65 70 75 80 Asp Val Cys Thr Val Ser Arg Thr Asp Arg Glu Thr Lys Leu Thr Leu 85 90 95 Val Phe Glu His Val Asp Gln Asp Leu Thr Thr Tyr Leu Asp Lys Val 100 105 110 Pro Glu Pro Gly Val Pro Thr Glu Thr Ile Lys Asp Met Met Phe Gln 115 120 125 Leu Leu Arg Gly Leu Asp Phe Leu His Ser His Arg Val Val His Arg 130 135 140 Asp Leu Lys Pro Gln Asn Ile Leu Val Thr Ser Ser Gly Gln Ile Lys 145 150 155 160 Leu Ala Asp Phe Gly Leu Ala Arg Ile Tyr Ser Phe Gln Met Ala Leu 165 170 175 Thr Ser Val Val Val Thr Leu Trp Tyr Arg Ala Pro Glu Val Leu Leu 180 185 190 Gln Ser Ser Tyr Ala Thr Pro Val Asp Leu Trp Ser Val Gly Cys Ile 195 200 205 Phe Ala Glu Met Phe Arg Arg Lys Pro Leu Phe Arg Gly Ser Ser Asp 210 215 220 Val Asp Gln Leu Gly Lys Ile Leu Asp Val Ile Gly Leu Pro Gly Glu 225 230 235 240 Glu Asp Trp Pro Arg Asp Val Ala Leu Pro Arg Gln Ala Phe His Ser 245 250 255 Lys Ser Ala Gln Pro Ile Glu Lys Phe Val Thr Asp Ile Asp Glu Leu 260 265 270 Gly Lys Asp Leu Leu Leu Lys Cys Leu Thr Phe Asn Pro Ala Lys Arg 275 280 285 Ile Ser Ala Tyr Ser Ala Leu Ser His Pro Tyr Phe Gln Asp Leu Glu 290 295 300 Arg Cys Lys Glu Asn Leu Asp Ser His Leu Pro Pro Ser Gln Asn Thr 305 310 315 320 Ser Glu Leu Asn Thr Ala 325 <210> SEQ ID NO 79 <211> LENGTH: 437 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 79 Met Ala Leu Ala Gly Ala Pro Ala Gly Gly Pro Cys Ala Pro Ala Leu 1 5 10 15 Glu Ala Leu Leu Gly Ala Gly Ala Leu Arg Leu Leu Asp Ser Ser Gln 20 25 30 Ile Val Ile Ile Ser Ala Ala Gln Asp Ala Ser Ala Pro Pro Ala Pro 35 40 45 Thr Gly Pro Ala Ala Pro Ala Ala Gly Pro Cys Asp Pro Asp Leu Leu 50 55 60 Leu Phe Ala Thr Pro Gln Ala Pro Arg Pro Thr Pro Ser Ala Pro Arg 65 70 75 80 Pro Ala Leu Gly Arg Pro Pro Val Lys Arg Arg Leu Asp Leu Glu Thr 85 90 95 Asp His Gln Tyr Leu Ala Glu Ser Ser Gly Pro Ala Arg Gly Arg Gly 100 105 110 Arg His Pro Gly Lys Gly Val Lys Ser Pro Gly Glu Lys Ser Arg Tyr 115 120 125 Glu Thr Ser Leu Asn Leu Thr Thr Lys Arg Phe Leu Glu Leu Leu Ser 130 135 140 His Ser Ala Asp Gly Val Val Asp Leu Asn Trp Ala Ala Glu Val Leu 145 150 155 160 Lys Val Gln Lys Arg Arg Ile Tyr Asp Ile Thr Asn Val Leu Glu Gly 165 170 175 Ile Gln Leu Ile Ala Lys Lys Ser Lys Asn His Ile Gln Trp Leu Gly 180 185 190 Ser His Thr Thr Val Gly Val Gly Gly Arg Leu Glu Gly Leu Thr Gln 195 200 205 Asp Leu Arg Gln Leu Gln Glu Ser Glu Gln Gln Leu Asp His Leu Met 210 215 220 Asn Ile Cys Thr Thr Gln Leu Arg Leu Leu Ser Glu Asp Thr Asp Ser 225 230 235 240 Gln Arg Leu Ala Tyr Val Thr Cys Gln Asp Leu Arg Ser Ile Ala Asp 245 250 255 Pro Ala Glu Gln Met Val Met Val Ile Lys Ala Pro Pro Glu Thr Gln 260 265 270 Leu Gln Ala Val Asp Ser Ser Glu Asn Phe Gln Ile Ser Leu Lys Ser 275 280 285 Lys Gln Gly Pro Ile Asp Val Phe Leu Cys Pro Glu Glu Thr Val Gly 290 295 300 Gly Ile Ser Pro Gly Lys Thr Pro Ser Gln Glu Val Thr Ser Glu Glu 305 310 315 320 Glu Asn Arg Ala Thr Asp Ser Ala Thr Ile Val Ser Pro Pro Pro Ser 325 330 335 Ser Pro Pro Ser Ser Leu Thr Thr Asp Pro Ser Gln Ser Leu Leu Ser 340 345 350 Leu Glu Gln Glu Pro Leu Leu Ser Arg Met Gly Ser Leu Arg Ala Pro 355 360 365 Val Asp Glu Asp Arg Leu Ser Pro Leu Val Ala Ala Asp Ser Leu Leu 370 375 380 Glu His Val Arg Glu Asp Phe Ser Gly Leu Leu Pro Glu Glu Phe Ile 385 390 395 400 Ser Leu Ser Pro Pro His Glu Ala Leu Asp Tyr His Phe Gly Leu Glu 405 410 415 Glu Gly Glu Gly Ile Arg Asp Leu Phe Asp Cys Asp Phe Gly Asp Leu 420 425 430 Thr Pro Leu Asp Phe 435 <210> SEQ ID NO 80 <211> LENGTH: 1170 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 80 Met Gly Leu Ala Trp Gly Leu Gly Val Leu Phe Leu Met His Val Cys 1 5 10 15 Gly Thr Asn Arg Ile Pro Glu Ser Gly Gly Asp Asn Ser Val Phe Asp 20 25 30 Ile Phe Glu Leu Thr Gly Ala Ala Arg Lys Gly Ser Gly Arg Arg Leu 35 40 45 Val Lys Gly Pro Asp Pro Ser Ser Pro Ala Phe Arg Ile Glu Asp Ala 50 55 60 Asn Leu Ile Pro Pro Val Pro Asp Asp Lys Phe Gln Asp Leu Val Asp 65 70 75 80 Ala Val Arg Ala Glu Lys Gly Phe Leu Leu Leu Ala Ser Leu Arg Gln 85 90 95 Met Lys Lys Thr Arg Gly Thr Leu Leu Ala Leu Glu Arg Lys Asp His 100 105 110 Ser Gly Gln Val Phe Ser Val Val Ser Asn Gly Lys Ala Gly Thr Leu 115 120 125 Asp Leu Ser Leu Thr Val Gln Gly Lys Gln His Val Val Ser Val Glu 130 135 140 Glu Ala Leu Leu Ala Thr Gly Gln Trp Lys Ser Ile Thr Leu Phe Val 145 150 155 160 Gln Glu Asp Arg Ala Gln Leu Tyr Ile Asp Cys Glu Lys Met Glu Asn 165 170 175 Ala Glu Leu Asp Val Pro Ile Gln Ser Val Phe Thr Arg Asp Leu Ala 180 185 190 Ser Ile Ala Arg Leu Arg Ile Ala Lys Gly Gly Val Asn Asp Asn Phe 195 200 205 Gln Gly Val Leu Gln Asn Val Arg Phe Val Phe Gly Thr Thr Pro Glu 210 215 220 Asp Ile Leu Arg Asn Lys Gly Cys Ser Ser Ser Thr Ser Val Leu Leu 225 230 235 240 Thr Leu Asp Asn Asn Val Val Asn Gly Ser Ser Pro Ala Ile Arg Thr 245 250 255 Asn Tyr Ile Gly His Lys Thr Lys Asp Leu Gln Ala Ile Cys Gly Ile 260 265 270 Ser Cys Asp Glu Leu Ser Ser Met Val Leu Glu Leu Arg Gly Leu Arg 275 280 285 Thr Ile Val Thr Thr Leu Gln Asp Ser Ile Arg Lys Val Thr Glu Glu 290 295 300 Asn Lys Glu Leu Ala Asn Glu Leu Arg Arg Pro Pro Leu Cys Tyr His 305 310 315 320 Asn Gly Val Gln Tyr Arg Asn Asn Glu Glu Trp Thr Val Asp Ser Cys 325 330 335 Thr Glu Cys His Cys Gln Asn Ser Val Thr Ile Cys Lys Lys Val Ser 340 345 350 Cys Pro Ile Met Pro Cys Ser Asn Ala Thr Val Pro Asp Gly Glu Cys 355 360 365 Cys Pro Arg Cys Trp Pro Ser Asp Ser Ala Asp Asp Gly Trp Ser Pro 370 375 380 Trp Ser Glu Trp Thr Ser Cys Ser Thr Ser Cys Gly Asn Gly Ile Gln 385 390 395 400 Gln Arg Gly Arg Ser Cys Asp Ser Leu Asn Asn Arg Cys Glu Gly Ser 405 410 415 Ser Val Gln Thr Arg Thr Cys His Ile Gln Glu Cys Asp Lys Arg Phe

420 425 430 Lys Gln Asp Gly Gly Trp Ser His Trp Ser Pro Trp Ser Ser Cys Ser 435 440 445 Val Thr Cys Gly Asp Gly Val Ile Thr Arg Ile Arg Leu Cys Asn Ser 450 455 460 Pro Ser Pro Gln Met Asn Gly Lys Pro Cys Glu Gly Glu Ala Arg Glu 465 470 475 480 Thr Lys Ala Cys Lys Lys Asp Ala Cys Pro Ile Asn Gly Gly Trp Gly 485 490 495 Pro Trp Ser Pro Trp Asp Ile Cys Ser Val Thr Cys Gly Gly Gly Val 500 505 510 Gln Lys Arg Ser Arg Leu Cys Asn Asn Pro Thr Pro Gln Phe Gly Gly 515 520 525 Lys Asp Cys Val Gly Asp Val Thr Glu Asn Gln Ile Cys Asn Lys Gln 530 535 540 Asp Cys Pro Ile Asp Gly Cys Leu Ser Asn Pro Cys Phe Ala Gly Val 545 550 555 560 Lys Cys Thr Ser Tyr Pro Asp Gly Ser Trp Lys Cys Gly Ala Cys Pro 565 570 575 Pro Gly Tyr Ser Gly Asn Gly Ile Gln Cys Thr Asp Val Asp Glu Cys 580 585 590 Lys Glu Val Pro Asp Ala Cys Phe Asn His Asn Gly Glu His Arg Cys 595 600 605 Glu Asn Thr Asp Pro Gly Tyr Asn Cys Leu Pro Cys Pro Pro Arg Phe 610 615 620 Thr Gly Ser Gln Pro Phe Gly Gln Gly Val Glu His Ala Thr Ala Asn 625 630 635 640 Lys Gln Val Cys Lys Pro Arg Asn Pro Cys Thr Asp Gly Thr His Asp 645 650 655 Cys Asn Lys Asn Ala Lys Cys Asn Tyr Leu Gly His Tyr Ser Asp Pro 660 665 670 Met Tyr Arg Cys Glu Cys Lys Pro Gly Tyr Ala Gly Asn Gly Ile Ile 675 680 685 Cys Gly Glu Asp Thr Asp Leu Asp Gly Trp Pro Asn Glu Asn Leu Val 690 695 700 Cys Val Ala Asn Ala Thr Tyr His Cys Lys Lys Asp Asn Cys Pro Asn 705 710 715 720 Leu Pro Asn Ser Gly Gln Glu Asp Tyr Asp Lys Asp Gly Ile Gly Asp 725 730 735 Ala Cys Asp Asp Asp Asp Asp Asn Asp Lys Ile Pro Asp Asp Arg Asp 740 745 750 Asn Cys Pro Phe His Tyr Asn Pro Ala Gln Tyr Asp Tyr Asp Arg Asp 755 760 765 Asp Val Gly Asp Arg Cys Asp Asn Cys Pro Tyr Asn His Asn Pro Asp 770 775 780 Gln Ala Asp Thr Asp Asn Asn Gly Glu Gly Asp Ala Cys Ala Ala Asp 785 790 795 800 Ile Asp Gly Asp Gly Ile Leu Asn Glu Arg Asp Asn Cys Gln Tyr Val 805 810 815 Tyr Asn Val Asp Gln Arg Asp Thr Asp Met Asp Gly Val Gly Asp Gln 820 825 830 Cys Asp Asn Cys Pro Leu Glu His Asn Pro Asp Gln Leu Asp Ser Asp 835 840 845 Ser Asp Arg Ile Gly Asp Thr Cys Asp Asn Asn Gln Asp Ile Asp Glu 850 855 860 Asp Gly His Gln Asn Asn Leu Asp Asn Cys Pro Tyr Val Pro Asn Ala 865 870 875 880 Asn Gln Ala Asp His Asp Lys Asp Gly Lys Gly Asp Ala Cys Asp His 885 890 895 Asp Asp Asp Asn Asp Gly Ile Pro Asp Asp Lys Asp Asn Cys Arg Leu 900 905 910 Val Pro Asn Pro Asp Gln Lys Asp Ser Asp Gly Asp Gly Arg Gly Asp 915 920 925 Ala Cys Lys Asp Asp Phe Asp His Asp Ser Val Pro Asp Ile Asp Asp 930 935 940 Ile Cys Pro Glu Asn Val Asp Ile Ser Glu Thr Asp Phe Arg Arg Phe 945 950 955 960 Gln Met Ile Pro Leu Asp Pro Lys Gly Thr Ser Gln Asn Asp Pro Asn 965 970 975 Trp Val Val Arg His Gln Gly Lys Glu Leu Val Gln Thr Val Asn Cys 980 985 990 Asp Pro Gly Leu Ala Val Gly Tyr Asp Glu Phe Asn Ala Val Asp Phe 995 1000 1005 Ser Gly Thr Phe Phe Ile Asn Thr Glu Arg Asp Asp Asp Tyr Ala Gly 1010 1015 1020 Phe Val Phe Gly Tyr Gln Ser Ser Ser Arg Phe Tyr Val Val Met Trp 1025 1030 1035 1040 Lys Gln Val Thr Gln Ser Tyr Trp Asp Thr Asn Pro Thr Arg Ala Gln 1045 1050 1055 Gly Tyr Ser Gly Leu Ser Val Lys Val Val Asn Ser Thr Thr Gly Pro 1060 1065 1070 Gly Glu His Leu Arg Asn Ala Leu Trp His Thr Gly Asn Thr Pro Gly 1075 1080 1085 Gln Val Arg Thr Leu Trp His Asp Pro Arg His Ile Gly Trp Lys Asp 1090 1095 1100 Phe Thr Ala Tyr Arg Trp Arg Leu Ser His Arg Pro Lys Thr Gly Phe 1105 1110 1115 1120 Ile Arg Val Val Met Tyr Glu Gly Lys Lys Ile Met Ala Asp Ser Gly 1125 1130 1135 Pro Ile Tyr Asp Lys Thr Tyr Ala Gly Gly Arg Leu Gly Leu Phe Val 1140 1145 1150 Phe Ser Gln Glu Met Val Phe Phe Ser Asp Leu Lys Tyr Glu Cys Arg 1155 1160 1165 Asp Pro 1170 <210> SEQ ID NO 81 <211> LENGTH: 1516 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 81 Met Ala Pro Tyr Pro Cys Gly Cys His Ile Leu Leu Leu Leu Phe Cys 1 5 10 15 Cys Leu Ala Ala Ala Arg Ala Asn Leu Leu Asn Leu Asn Trp Leu Trp 20 25 30 Phe Asn Asn Glu Asp Thr Ser His Ala Ala Thr Thr Ile Pro Glu Pro 35 40 45 Gln Gly Pro Leu Pro Val Gln Pro Thr Ala Asp Thr Thr Thr His Val 50 55 60 Thr Pro Arg Asn Gly Ser Thr Glu Pro Ala Thr Ala Pro Gly Ser Pro 65 70 75 80 Glu Pro Pro Ser Glu Leu Leu Glu Asp Gly Gln Asp Thr Pro Thr Ser 85 90 95 Ala Glu Ser Pro Asp Ala Pro Glu Glu Asn Ile Ala Gly Val Gly Ala 100 105 110 Glu Ile Leu Asn Val Ala Lys Gly Ile Arg Ser Phe Val Gln Leu Trp 115 120 125 Asn Asp Thr Val Pro Thr Glu Ser Leu Ala Arg Ala Glu Thr Leu Val 130 135 140 Leu Glu Thr Pro Val Gly Pro Leu Ala Leu Ala Gly Pro Ser Ser Thr 145 150 155 160 Pro Gln Glu Asn Gly Thr Thr Leu Trp Pro Ser Arg Gly Ile Pro Ser 165 170 175 Ser Pro Gly Ala His Thr Thr Glu Ala Gly Thr Leu Pro Ala Pro Thr 180 185 190 Pro Ser Pro Pro Ser Leu Gly Arg Pro Trp Ala Pro Leu Thr Gly Pro 195 200 205 Ser Val Pro Pro Pro Ser Ser Glu Arg Ile Ser Glu Glu Val Gly Leu 210 215 220 Leu Gln Leu Leu Gly Asp Pro Pro Pro Gln Gln Val Thr Gln Thr Asp 225 230 235 240 Asp Pro Asp Val Gly Leu Ala Tyr Val Phe Gly Pro Asp Ala Asn Ser 245 250 255 Gly Gln Val Ala Arg Tyr His Phe Pro Ser Leu Phe Phe Arg Asp Phe 260 265 270 Ser Leu Leu Phe His Ile Arg Pro Ala Thr Glu Gly Pro Gly Val Leu 275 280 285 Phe Ala Ile Thr Asp Ser Ala Gln Ala Met Val Leu Leu Gly Val Lys 290 295 300 Leu Ser Gly Val Gln Asp Gly His Gln Asp Ile Ser Leu Leu Tyr Thr 305 310 315 320 Glu Pro Gly Ala Gly Gln Thr His Thr Ala Ala Ser Phe Arg Leu Pro 325 330 335 Ala Phe Val Gly Gln Trp Thr His Leu Ala Leu Ser Val Ala Gly Gly 340 345 350 Phe Val Ala Leu Tyr Val Asp Cys Glu Glu Phe Gln Arg Met Pro Leu 355 360 365 Ala Arg Ser Ser Arg Gly Leu Glu Leu Glu Pro Gly Ala Gly Leu Phe 370 375 380 Val Ala Gln Ala Gly Gly Ala Asp Pro Asp Lys Phe Gln Gly Val Ile 385 390 395 400 Ala Glu Leu Lys Val Arg Arg Asp Pro Gln Val Ser Pro Met His Cys 405 410 415 Leu Asp Glu Glu Gly Asp Asp Ser Asp Gly Ala Ser Gly Asp Ser Gly 420 425 430 Ser Gly Leu Gly Asp Ala Arg Glu Leu Leu Arg Glu Glu Thr Gly Ala 435 440 445 Ala Leu Lys Pro Arg Leu Pro Ala Pro Pro Pro Val Thr Thr Pro Pro 450 455 460 Leu Ala Gly Gly Ser Ser Thr Glu Asp Ser Arg Ser Glu Glu Val Glu 465 470 475 480 Glu Gln Thr Thr Val Ala Ser Leu Gly Ala Gln Thr Leu Pro Gly Ser 485 490 495 Asp Ser Val Ser Thr Trp Asp Gly Ser Val Arg Thr Pro Gly Gly Arg 500 505 510 Val Lys Glu Gly Gly Leu Lys Gly Gln Lys Gly Glu Pro Gly Val Pro 515 520 525 Gly Pro Pro Gly Arg Ala Gly Pro Pro Gly Ser Pro Cys Leu Pro Gly

530 535 540 Pro Pro Gly Leu Pro Cys Pro Val Ser Pro Leu Gly Pro Ala Gly Pro 545 550 555 560 Ala Leu Gln Thr Val Pro Gly Pro Gln Gly Pro Pro Gly Pro Pro Gly 565 570 575 Arg Asp Gly Thr Pro Gly Arg Asp Gly Glu Pro Gly Asp Pro Gly Glu 580 585 590 Asp Gly Lys Pro Gly Asp Thr Gly Pro Gln Gly Phe Pro Gly Thr Pro 595 600 605 Gly Asp Val Gly Pro Lys Gly Asp Lys Gly Asp Pro Gly Val Gly Glu 610 615 620 Arg Gly Pro Pro Gly Pro Gln Gly Pro Pro Gly Pro Pro Gly Pro Ser 625 630 635 640 Phe Arg His Asp Lys Leu Thr Phe Ile Asp Met Glu Gly Ser Gly Phe 645 650 655 Gly Gly Asp Leu Glu Ala Leu Arg Gly Pro Arg Gly Phe Pro Gly Pro 660 665 670 Pro Gly Pro Pro Gly Val Pro Gly Leu Pro Gly Glu Pro Gly Arg Phe 675 680 685 Gly Val Asn Ser Ser Asp Val Pro Gly Pro Ala Gly Leu Pro Gly Val 690 695 700 Pro Gly Arg Glu Gly Pro Pro Gly Phe Pro Gly Leu Pro Gly Pro Pro 705 710 715 720 Gly Pro Pro Gly Arg Glu Gly Pro Pro Gly Arg Thr Gly Gln Lys Gly 725 730 735 Ser Leu Gly Glu Ala Gly Ala Pro Gly His Lys Gly Ser Lys Gly Ala 740 745 750 Pro Gly Pro Ala Gly Ala Arg Gly Glu Ser Gly Leu Ala Gly Ala Pro 755 760 765 Gly Pro Ala Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly 770 775 780 Pro Gly Leu Pro Ala Gly Phe Asp Asp Met Glu Gly Ser Gly Gly Pro 785 790 795 800 Phe Trp Ser Thr Ala Arg Ser Ala Asp Gly Pro Gln Gly Pro Pro Gly 805 810 815 Leu Pro Gly Leu Lys Gly Asp Pro Gly Val Pro Gly Leu Pro Gly Ala 820 825 830 Lys Gly Glu Val Gly Ala Asp Gly Val Pro Gly Phe Pro Gly Leu Pro 835 840 845 Gly Arg Glu Gly Ile Ala Gly Pro Gln Gly Pro Lys Gly Asp Arg Gly 850 855 860 Ser Arg Gly Glu Lys Gly Asp Pro Gly Lys Asp Gly Val Gly Gln Pro 865 870 875 880 Gly Leu Pro Gly Pro Pro Gly Pro Pro Gly Pro Val Val Tyr Val Ser 885 890 895 Glu Gln Asp Gly Ser Val Leu Ser Val Pro Gly Pro Glu Gly Arg Pro 900 905 910 Gly Phe Ala Gly Phe Pro Gly Pro Ala Gly Pro Lys Gly Asn Leu Gly 915 920 925 Ser Lys Gly Glu Arg Gly Ser Pro Gly Pro Lys Gly Glu Lys Gly Glu 930 935 940 Pro Gly Ser Ile Phe Ser Pro Asp Gly Gly Ala Leu Gly Pro Ala Gln 945 950 955 960 Lys Gly Ala Lys Gly Glu Pro Gly Phe Arg Gly Pro Pro Gly Pro Tyr 965 970 975 Gly Arg Pro Gly Tyr Lys Gly Glu Ile Gly Phe Pro Gly Arg Pro Gly 980 985 990 Arg Pro Gly Met Asn Gly Leu Lys Gly Glu Lys Gly Glu Pro Gly Asp 995 1000 1005 Ala Ser Leu Gly Phe Gly Met Arg Gly Met Pro Gly Pro Pro Gly Pro 1010 1015 1020 Pro Gly Pro Pro Gly Pro Pro Gly Thr Pro Val Tyr Asp Ser Asn Val 1025 1030 1035 1040 Phe Ala Glu Ser Ser Arg Pro Gly Pro Pro Gly Leu Pro Gly Asn Gln 1045 1050 1055 Gly Pro Pro Gly Pro Lys Gly Ala Lys Gly Glu Val Gly Pro Pro Gly 1060 1065 1070 Pro Pro Gly Gln Phe Pro Phe Asp Phe Leu Gln Leu Glu Ala Glu Met 1075 1080 1085 Lys Gly Glu Lys Gly Asp Arg Gly Asp Ala Gly Gln Lys Gly Glu Arg 1090 1095 1100 Gly Glu Pro Gly Gly Gly Gly Phe Phe Gly Ser Ser Leu Pro Gly Pro 1105 1110 1115 1120 Pro Gly Pro Pro Gly Pro Arg Gly Tyr Pro Gly Ile Pro Gly Pro Lys 1125 1130 1135 Gly Glu Ser Ile Arg Gly Gln Pro Gly Pro Pro Gly Pro Gln Gly Pro 1140 1145 1150 Pro Gly Ile Gly Tyr Glu Gly Arg Gln Gly Pro Pro Gly Pro Pro Gly 1155 1160 1165 Pro Pro Gly Pro Pro Ser Phe Pro Gly Pro His Arg Gln Thr Ile Ser 1170 1175 1180 Val Pro Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly Thr 1185 1190 1195 1200 Met Gly Ala Ser Ser Gly Val Arg Leu Trp Ala Thr Arg Gln Ala Met 1205 1210 1215 Leu Gly Gln Val His Glu Val Pro Glu Gly Trp Leu Ile Phe Val Ala 1220 1225 1230 Glu Gln Glu Glu Leu Tyr Val Arg Val Gln Asn Gly Phe Arg Lys Val 1235 1240 1245 Gln Leu Glu Ala Arg Thr Pro Leu Pro Arg Gly Thr Asp Asn Glu Val 1250 1255 1260 Ala Ala Leu Gln Pro Pro Val Val Gln Leu His Asp Ser Asn Pro Tyr 1265 1270 1275 1280 Pro Arg Arg Glu His Pro His Pro Thr Ala Arg Pro Trp Arg Ala Asp 1285 1290 1295 Asp Ile Leu Ala Ser Pro Pro Arg Leu Pro Glu Pro Gln Pro Tyr Pro 1300 1305 1310 Gly Ala Pro His His Ser Ser Tyr Val His Leu Arg Pro Ala Arg Pro 1315 1320 1325 Thr Ser Pro Pro Ala His Ser His Arg Asp Phe Gln Pro Val Leu His 1330 1335 1340 Leu Val Ala Leu Asn Ser Pro Leu Ser Gly Gly Met Arg Gly Ile Arg 1345 1350 1355 1360 Gly Ala Asp Phe Gln Cys Phe Gln Gln Ala Arg Ala Val Gly Leu Ala 1365 1370 1375 Gly Thr Phe Arg Ala Phe Leu Ser Ser Arg Leu Gln Asp Leu Tyr Ser 1380 1385 1390 Ile Val Arg Arg Ala Asp Arg Ala Ala Val Pro Ile Val Asn Leu Lys 1395 1400 1405 Asp Glu Leu Leu Phe Pro Ser Trp Glu Ala Leu Phe Ser Gly Ser Glu 1410 1415 1420 Gly Pro Leu Lys Pro Gly Ala Arg Ile Phe Ser Phe Asp Gly Lys Asp 1425 1430 1435 1440 Val Leu Arg His Pro Thr Trp Pro Gln Lys Ser Val Trp His Gly Ser 1445 1450 1455 Asp Pro Asn Gly Arg Arg Leu Thr Glu Ser Tyr Cys Glu Thr Trp Arg 1460 1465 1470 Thr Glu Ala Pro Ser Ala Thr Gly Gln Ala Ser Ser Leu Leu Gly Gly 1475 1480 1485 Arg Leu Leu Gly Gln Ser Ala Ala Ser Cys His His Ala Tyr Ile Val 1490 1495 1500 Leu Cys Ile Glu Asn Ser Phe Met Thr Ala Ser Lys 1505 1510 1515 <210> SEQ ID NO 82 <211> LENGTH: 1336 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 82 Met Ala Pro Arg Cys Pro Trp Pro Trp Pro Arg Arg Arg Arg Leu Leu 1 5 10 15 Asp Val Leu Ala Pro Leu Val Leu Leu Leu Gly Val Arg Ala Ala Ser 20 25 30 Ala Glu Pro Glu Arg Ile Ser Glu Glu Val Gly Leu Leu Gln Leu Leu 35 40 45 Gly Asp Pro Pro Pro Gln Gln Val Thr Gln Thr Asp Asp Pro Asp Val 50 55 60 Gly Leu Ala Tyr Val Phe Gly Pro Asp Ala Asn Ser Gly Gln Val Ala 65 70 75 80 Arg Tyr His Phe Pro Ser Leu Phe Phe Arg Asp Phe Ser Leu Leu Phe 85 90 95 His Ile Arg Pro Ala Thr Glu Gly Pro Gly Val Leu Phe Ala Ile Thr 100 105 110 Asp Ser Ala Gln Ala Met Val Leu Leu Gly Val Lys Leu Ser Gly Val 115 120 125 Gln Asp Gly His Gln Asp Ile Ser Leu Leu Tyr Thr Glu Pro Gly Ala 130 135 140 Gly Gln Thr His Thr Ala Ala Ser Phe Arg Leu Pro Ala Phe Val Gly 145 150 155 160 Gln Trp Thr His Leu Ala Leu Ser Val Ala Gly Gly Phe Val Ala Leu 165 170 175 Tyr Val Asp Cys Glu Glu Phe Gln Arg Met Pro Leu Ala Arg Ser Ser 180 185 190 Arg Gly Leu Glu Leu Glu Pro Gly Ala Gly Leu Phe Val Ala Gln Ala 195 200 205 Gly Gly Ala Asp Pro Asp Lys Phe Gln Gly Val Ile Ala Glu Leu Lys 210 215 220 Val Arg Arg Asp Pro Gln Val Ser Pro Met His Cys Leu Asp Glu Glu 225 230 235 240 Gly Asp Asp Ser Asp Gly Ala Ser Gly Asp Ser Gly Ser Gly Leu Gly 245 250 255 Asp Ala Arg Glu Leu Leu Arg Glu Glu Thr Gly Ala Ala Leu Lys Pro 260 265 270 Arg Leu Pro Ala Pro Pro Pro Val Thr Thr Pro Pro Leu Ala Gly Gly 275 280 285 Ser Ser Thr Glu Asp Ser Arg Ser Glu Glu Val Glu Glu Gln Thr Thr 290 295 300 Val Ala Ser Leu Gly Ala Gln Thr Leu Pro Gly Ser Asp Ser Val Ser

305 310 315 320 Thr Trp Asp Gly Ser Val Arg Thr Pro Gly Gly Arg Val Lys Glu Gly 325 330 335 Gly Leu Lys Gly Gln Lys Gly Glu Pro Gly Val Pro Gly Pro Pro Gly 340 345 350 Arg Ala Gly Pro Pro Gly Ser Pro Cys Leu Pro Gly Pro Pro Gly Leu 355 360 365 Pro Cys Pro Val Ser Pro Leu Gly Pro Ala Gly Pro Ala Leu Gln Thr 370 375 380 Val Pro Gly Pro Gln Gly Pro Pro Gly Pro Pro Gly Arg Asp Gly Thr 385 390 395 400 Pro Gly Arg Asp Gly Glu Pro Gly Asp Pro Gly Glu Asp Gly Lys Pro 405 410 415 Gly Asp Thr Gly Pro Gln Gly Phe Pro Gly Thr Pro Gly Asp Val Gly 420 425 430 Pro Lys Gly Asp Lys Gly Asp Pro Gly Val Gly Glu Arg Gly Pro Pro 435 440 445 Gly Pro Gln Gly Pro Pro Gly Pro Pro Gly Pro Ser Phe Arg His Asp 450 455 460 Lys Leu Thr Phe Ile Asp Met Glu Gly Ser Gly Phe Gly Gly Asp Leu 465 470 475 480 Glu Ala Leu Arg Gly Pro Arg Gly Phe Pro Gly Pro Pro Gly Pro Pro 485 490 495 Gly Val Pro Gly Leu Pro Gly Glu Pro Gly Arg Phe Gly Val Asn Ser 500 505 510 Ser Asp Val Pro Gly Pro Ala Gly Leu Pro Gly Val Pro Gly Arg Glu 515 520 525 Gly Pro Pro Gly Phe Pro Gly Leu Pro Gly Pro Pro Gly Pro Pro Gly 530 535 540 Arg Glu Gly Pro Pro Gly Arg Thr Gly Gln Lys Gly Ser Leu Gly Glu 545 550 555 560 Ala Gly Ala Pro Gly His Lys Gly Ser Lys Gly Ala Pro Gly Pro Ala 565 570 575 Gly Ala Arg Gly Glu Ser Gly Leu Ala Gly Ala Pro Gly Pro Ala Gly 580 585 590 Pro Pro Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly Pro Gly Leu Pro 595 600 605 Ala Gly Phe Asp Asp Met Glu Gly Ser Gly Gly Pro Phe Trp Ser Thr 610 615 620 Ala Arg Ser Ala Asp Gly Pro Gln Gly Pro Pro Gly Leu Pro Gly Leu 625 630 635 640 Lys Gly Asp Pro Gly Val Pro Gly Leu Pro Gly Ala Lys Gly Glu Val 645 650 655 Gly Ala Asp Gly Val Pro Gly Phe Pro Gly Leu Pro Gly Arg Glu Gly 660 665 670 Ile Ala Gly Pro Gln Gly Pro Lys Gly Asp Arg Gly Ser Arg Gly Glu 675 680 685 Lys Gly Asp Pro Gly Lys Asp Gly Val Gly Gln Pro Gly Leu Pro Gly 690 695 700 Pro Pro Gly Pro Pro Gly Pro Val Val Tyr Val Ser Glu Gln Asp Gly 705 710 715 720 Ser Val Leu Ser Val Pro Gly Pro Glu Gly Arg Pro Gly Phe Ala Gly 725 730 735 Phe Pro Gly Pro Ala Gly Pro Lys Gly Asn Leu Gly Ser Lys Gly Glu 740 745 750 Arg Gly Ser Pro Gly Pro Lys Gly Glu Lys Gly Glu Pro Gly Ser Ile 755 760 765 Phe Ser Pro Asp Gly Gly Ala Leu Gly Pro Ala Gln Lys Gly Ala Lys 770 775 780 Gly Glu Pro Gly Phe Arg Gly Pro Pro Gly Pro Tyr Gly Arg Pro Gly 785 790 795 800 Tyr Lys Gly Glu Ile Gly Phe Pro Gly Arg Pro Gly Arg Pro Gly Met 805 810 815 Asn Gly Leu Lys Gly Glu Lys Gly Glu Pro Gly Asp Ala Ser Leu Gly 820 825 830 Phe Gly Met Arg Gly Met Pro Gly Pro Pro Gly Pro Pro Gly Pro Pro 835 840 845 Gly Pro Pro Gly Thr Pro Val Tyr Asp Ser Asn Val Phe Ala Glu Ser 850 855 860 Ser Arg Pro Gly Pro Pro Gly Leu Pro Gly Asn Gln Gly Pro Pro Gly 865 870 875 880 Pro Lys Gly Ala Lys Gly Glu Val Gly Pro Pro Gly Pro Pro Gly Gln 885 890 895 Phe Pro Phe Asp Phe Leu Gln Leu Glu Ala Glu Met Lys Gly Glu Lys 900 905 910 Gly Asp Arg Gly Asp Ala Gly Gln Lys Gly Glu Arg Gly Glu Pro Gly 915 920 925 Gly Gly Gly Phe Phe Gly Ser Ser Leu Pro Gly Pro Pro Gly Pro Pro 930 935 940 Gly Pro Arg Gly Tyr Pro Gly Ile Pro Gly Pro Lys Gly Glu Ser Ile 945 950 955 960 Arg Gly Gln Pro Gly Pro Pro Gly Pro Gln Gly Pro Pro Gly Ile Gly 965 970 975 Tyr Glu Gly Arg Gln Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly Pro 980 985 990 Pro Ser Phe Pro Gly Pro His Arg Gln Thr Ile Ser Val Pro Gly Pro 995 1000 1005 Pro Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly Thr Met Gly Ala Ser 1010 1015 1020 Ser Gly Val Arg Leu Trp Ala Thr Arg Gln Ala Met Leu Gly Gln Val 1025 1030 1035 1040 His Glu Val Pro Glu Gly Trp Leu Ile Phe Val Ala Glu Gln Glu Glu 1045 1050 1055 Leu Tyr Val Arg Val Gln Asn Gly Phe Arg Lys Val Gln Leu Glu Ala 1060 1065 1070 Arg Thr Pro Leu Pro Arg Gly Thr Asp Asn Glu Val Ala Ala Leu Gln 1075 1080 1085 Pro Pro Val Val Gln Leu His Asp Ser Asn Pro Tyr Pro Arg Arg Glu 1090 1095 1100 His Pro His Pro Thr Ala Arg Pro Trp Arg Ala Asp Asp Ile Leu Ala 1105 1110 1115 1120 Ser Pro Pro Arg Leu Pro Glu Pro Gln Pro Tyr Pro Gly Ala Pro His 1125 1130 1135 His Ser Ser Tyr Val His Leu Arg Pro Ala Arg Pro Thr Ser Pro Pro 1140 1145 1150 Ala His Ser His Arg Asp Phe Gln Pro Val Leu His Leu Val Ala Leu 1155 1160 1165 Asn Ser Pro Leu Ser Gly Gly Met Arg Gly Ile Arg Gly Ala Asp Phe 1170 1175 1180 Gln Cys Phe Gln Gln Ala Arg Ala Val Gly Leu Ala Gly Thr Phe Arg 1185 1190 1195 1200 Ala Phe Leu Ser Ser Arg Leu Gln Asp Leu Tyr Ser Ile Val Arg Arg 1205 1210 1215 Ala Asp Arg Ala Ala Val Pro Ile Val Asn Leu Lys Asp Glu Leu Leu 1220 1225 1230 Phe Pro Ser Trp Glu Ala Leu Phe Ser Gly Ser Glu Gly Pro Leu Lys 1235 1240 1245 Pro Gly Ala Arg Ile Phe Ser Phe Asp Gly Lys Asp Val Leu Arg His 1250 1255 1260 Pro Thr Trp Pro Gln Lys Ser Val Trp His Gly Ser Asp Pro Asn Gly 1265 1270 1275 1280 Arg Arg Leu Thr Glu Ser Tyr Cys Glu Thr Trp Arg Thr Glu Ala Pro 1285 1290 1295 Ser Ala Thr Gly Gln Ala Ser Ser Leu Leu Gly Gly Arg Leu Leu Gly 1300 1305 1310 Gln Ser Ala Ala Ser Cys His His Ala Tyr Ile Val Leu Cys Ile Glu 1315 1320 1325 Asn Ser Phe Met Thr Ala Ser Lys 1330 1335 <210> SEQ ID NO 83 <211> LENGTH: 1670 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 83 Met Ser Ala Arg Thr Ala Pro Arg Pro Gln Val Leu Leu Leu Pro Leu 1 5 10 15 Leu Leu Val Leu Leu Ala Ala Ala Pro Ala Ala Ser Lys Gly Cys Val 20 25 30 Cys Lys Asp Lys Gly Gln Cys Phe Cys Asp Gly Ala Lys Gly Glu Lys 35 40 45 Gly Glu Lys Gly Phe Pro Gly Pro Pro Gly Ser Pro Gly Gln Lys Gly 50 55 60 Phe Thr Gly Pro Glu Gly Leu Pro Gly Pro Gln Gly Pro Lys Gly Phe 65 70 75 80 Pro Gly Leu Pro Gly Leu Thr Gly Ser Lys Gly Val Arg Gly Ile Ser 85 90 95 Gly Leu Pro Gly Phe Ser Gly Ser Pro Gly Leu Pro Gly Thr Pro Gly 100 105 110 Asn Thr Gly Pro Tyr Gly Leu Val Gly Val Pro Gly Cys Ser Gly Ser 115 120 125 Lys Gly Glu Gln Gly Phe Pro Gly Leu Pro Gly Thr Leu Gly Tyr Pro 130 135 140 Gly Ile Pro Gly Ala Ala Gly Leu Lys Gly Gln Lys Gly Ala Pro Ala 145 150 155 160 Lys Glu Glu Asp Ile Glu Leu Asp Ala Lys Gly Asp Pro Gly Leu Pro 165 170 175 Gly Ala Pro Gly Pro Gln Gly Leu Pro Gly Pro Pro Gly Phe Pro Gly 180 185 190 Pro Val Gly Pro Pro Gly Pro Pro Gly Phe Phe Gly Phe Pro Gly Ala 195 200 205 Met Gly Pro Arg Gly Pro Lys Gly His Met Gly Glu Arg Val Ile Gly 210 215 220 His Lys Gly Glu Arg Gly Val Lys Gly Leu Thr Gly Pro Pro Gly Pro 225 230 235 240 Pro Gly Thr Val Ile Val Thr Leu Thr Gly Pro Asp Asn Arg Thr Asp 245 250 255 Leu Lys Gly Glu Lys Gly Asp Lys Gly Ala Met Gly Glu Pro Gly Pro

260 265 270 Pro Gly Pro Ser Gly Leu Pro Gly Glu Ser Tyr Gly Ser Glu Lys Gly 275 280 285 Ala Pro Gly Asp Pro Gly Leu Gln Gly Lys Pro Gly Lys Asp Gly Val 290 295 300 Pro Gly Phe Pro Gly Ser Glu Gly Val Lys Gly Asn Arg Gly Phe Pro 305 310 315 320 Gly Leu Met Gly Glu Asp Gly Ile Lys Gly Gln Lys Gly Asp Ile Gly 325 330 335 Pro Pro Gly Phe Arg Gly Pro Thr Glu Tyr Tyr Asp Thr Tyr Gln Glu 340 345 350 Lys Gly Asp Glu Gly Thr Pro Gly Pro Pro Gly Pro Arg Gly Ala Arg 355 360 365 Gly Pro Gln Gly Pro Ser Gly Pro Pro Gly Val Pro Gly Ser Pro Gly 370 375 380 Ser Ser Arg Pro Gly Leu Arg Gly Ala Pro Gly Trp Pro Gly Leu Lys 385 390 395 400 Gly Ser Lys Gly Glu Arg Gly Arg Pro Gly Lys Asp Ala Met Gly Thr 405 410 415 Pro Gly Ser Pro Gly Cys Ala Gly Ser Pro Gly Leu Pro Gly Ser Pro 420 425 430 Gly Pro Pro Gly Pro Pro Gly Asp Ile Val Phe Arg Lys Gly Pro Pro 435 440 445 Gly Asp His Gly Leu Pro Gly Tyr Leu Gly Ser Pro Gly Ile Pro Gly 450 455 460 Val Asp Gly Pro Lys Gly Glu Pro Gly Leu Leu Cys Thr Gln Cys Pro 465 470 475 480 Tyr Ile Pro Gly Pro Pro Gly Leu Pro Gly Leu Pro Gly Leu His Gly 485 490 495 Val Lys Gly Ile Pro Gly Arg Gln Gly Ala Ala Gly Leu Lys Gly Ser 500 505 510 Pro Gly Ser Pro Gly Asn Thr Gly Leu Pro Gly Phe Pro Gly Phe Pro 515 520 525 Gly Ala Gln Gly Asp Pro Gly Leu Lys Gly Glu Lys Gly Glu Thr Leu 530 535 540 Gln Pro Glu Gly Gln Val Gly Val Pro Gly Asp Pro Gly Leu Arg Gly 545 550 555 560 Gln Pro Gly Arg Lys Gly Leu Asp Gly Ile Pro Gly Thr Pro Gly Val 565 570 575 Lys Gly Leu Pro Gly Pro Lys Gly Glu Leu Ala Leu Ser Gly Glu Lys 580 585 590 Gly Asp Gln Gly Pro Pro Gly Asp Pro Gly Ser Pro Gly Ser Pro Gly 595 600 605 Pro Ala Gly Pro Ala Gly Pro Pro Gly Tyr Gly Pro Gln Gly Glu Pro 610 615 620 Gly Leu Gln Gly Thr Gln Gly Val Pro Gly Ala Pro Gly Pro Pro Gly 625 630 635 640 Glu Ala Gly Pro Arg Gly Glu Leu Ser Val Ser Thr Pro Val Pro Gly 645 650 655 Pro Pro Gly Pro Pro Gly Pro Pro Gly His Pro Gly Pro Gln Gly Pro 660 665 670 Pro Gly Ile Pro Gly Ser Leu Gly Lys Cys Gly Asp Pro Gly Leu Pro 675 680 685 Gly Pro Asp Gly Glu Pro Gly Ile Pro Gly Ile Gly Phe Pro Gly Pro 690 695 700 Pro Gly Pro Lys Gly Asp Gln Gly Phe Pro Gly Thr Lys Gly Ser Leu 705 710 715 720 Gly Cys Pro Gly Lys Met Gly Glu Pro Gly Leu Pro Gly Lys Pro Gly 725 730 735 Leu Pro Gly Ala Lys Gly Glu Pro Ala Val Ala Met Pro Gly Gly Pro 740 745 750 Gly Thr Pro Gly Phe Pro Gly Glu Arg Gly Asn Ser Gly Glu His Gly 755 760 765 Glu Ile Gly Leu Pro Gly Leu Pro Gly Leu Pro Gly Thr Pro Gly Asn 770 775 780 Glu Gly Leu Asp Gly Pro Arg Gly Asp Pro Gly Gln Pro Gly Pro Pro 785 790 795 800 Gly Glu Gln Gly Pro Pro Gly Arg Cys Ile Glu Gly Pro Arg Gly Ala 805 810 815 Gln Gly Leu Pro Gly Leu Asn Gly Leu Lys Gly Gln Gln Gly Arg Arg 820 825 830 Gly Lys Thr Gly Pro Lys Gly Asp Pro Gly Ile Pro Gly Leu Asp Arg 835 840 845 Ser Gly Phe Pro Gly Glu Thr Gly Ser Pro Gly Ile Pro Gly His Gln 850 855 860 Gly Glu Met Gly Pro Leu Gly Gln Arg Gly Tyr Pro Gly Asn Pro Gly 865 870 875 880 Ile Leu Gly Pro Pro Gly Glu Asp Gly Val Ile Gly Met Met Gly Phe 885 890 895 Pro Gly Ala Ile Gly Pro Pro Gly Pro Pro Gly Asn Pro Gly Thr Pro 900 905 910 Gly Gln Arg Gly Ser Pro Gly Ile Pro Gly Val Lys Gly Gln Arg Gly 915 920 925 Thr Pro Gly Ala Lys Gly Glu Gln Gly Asp Lys Gly Asn Pro Gly Pro 930 935 940 Ser Glu Ile Ser His Val Ile Gly Asp Lys Gly Glu Pro Gly Leu Lys 945 950 955 960 Gly Phe Ala Gly Asn Pro Gly Glu Lys Gly Asn Arg Gly Val Pro Gly 965 970 975 Met Pro Gly Leu Lys Gly Leu Lys Gly Leu Pro Gly Pro Ala Gly Pro 980 985 990 Pro Gly Pro Arg Gly Asp Leu Gly Ser Thr Gly Asn Pro Gly Glu Pro 995 1000 1005 Gly Leu Arg Gly Ile Pro Gly Ser Met Gly Asn Met Gly Met Pro Gly 1010 1015 1020 Ser Lys Gly Lys Arg Gly Thr Leu Gly Phe Pro Gly Arg Ala Gly Arg 1025 1030 1035 1040 Pro Gly Leu Pro Gly Ile His Gly Leu Gln Gly Asp Lys Gly Glu Pro 1045 1050 1055 Gly Tyr Ser Glu Gly Thr Arg Pro Gly Pro Pro Gly Pro Thr Gly Asp 1060 1065 1070 Pro Gly Leu Pro Gly Asp Met Gly Lys Lys Gly Glu Met Gly Gln Pro 1075 1080 1085 Gly Pro Pro Gly His Leu Gly Pro Ala Gly Pro Glu Gly Ala Pro Gly 1090 1095 1100 Ser Pro Gly Ser Pro Gly Leu Pro Gly Lys Pro Gly Pro His Gly Asp 1105 1110 1115 1120 Leu Gly Phe Lys Gly Ile Lys Gly Leu Leu Gly Pro Pro Gly Ile Arg 1125 1130 1135 Gly Pro Pro Gly Leu Pro Gly Phe Pro Gly Ser Pro Gly Pro Met Gly 1140 1145 1150 Ile Arg Gly Asp Gln Gly Arg Asp Gly Ile Pro Gly Pro Ala Gly Glu 1155 1160 1165 Lys Gly Glu Thr Gly Leu Leu Arg Ala Pro Pro Gly Pro Arg Gly Asn 1170 1175 1180 Pro Gly Ala Gln Gly Ala Lys Gly Asp Arg Gly Ala Pro Gly Phe Pro 1185 1190 1195 1200 Gly Leu Pro Gly Arg Lys Gly Ala Met Gly Asp Ala Gly Pro Arg Gly 1205 1210 1215 Pro Thr Gly Ile Glu Gly Phe Pro Gly Pro Pro Gly Leu Pro Gly Ala 1220 1225 1230 Ile Ile Pro Gly Gln Thr Gly Asn Arg Gly Pro Pro Gly Ser Arg Gly 1235 1240 1245 Ser Pro Gly Ala Pro Gly Pro Pro Gly Pro Pro Gly Ser His Val Ile 1250 1255 1260 Gly Ile Lys Gly Asp Lys Gly Ser Met Gly His Pro Gly Pro Lys Gly 1265 1270 1275 1280 Pro Pro Gly Thr Ala Gly Asp Met Gly Pro Pro Gly Arg Leu Gly Ala 1285 1290 1295 Pro Gly Thr Pro Gly Leu Pro Gly Pro Arg Gly Asp Pro Gly Phe Gln 1300 1305 1310 Gly Phe Pro Gly Val Lys Gly Glu Lys Gly Asn Pro Gly Phe Leu Gly 1315 1320 1325 Ser Ile Gly Pro Pro Gly Pro Ile Gly Pro Lys Gly Pro Pro Gly Val 1330 1335 1340 Arg Gly Asp Pro Gly Thr Leu Lys Ile Ile Ser Leu Pro Gly Ser Pro 1345 1350 1355 1360 Gly Pro Pro Gly Thr Pro Gly Glu Pro Gly Met Gln Gly Glu Pro Gly 1365 1370 1375 Pro Pro Gly Pro Pro Gly Asn Leu Gly Pro Cys Gly Pro Arg Gly Lys 1380 1385 1390 Pro Gly Lys Asp Gly Lys Pro Gly Thr Pro Gly Pro Ala Gly Glu Lys 1395 1400 1405 Gly Asn Lys Gly Ser Lys Gly Glu Pro Gly Pro Ala Gly Ser Asp Gly 1410 1415 1420 Leu Pro Gly Leu Lys Gly Lys Arg Gly Asp Ser Gly Ser Pro Ala Thr 1425 1430 1435 1440 Trp Thr Thr Arg Gly Phe Val Phe Thr Arg His Ser Gln Thr Thr Ala 1445 1450 1455 Ile Pro Ser Cys Pro Glu Gly Thr Val Pro Leu Tyr Ser Gly Phe Ser 1460 1465 1470 Phe Leu Phe Val Gln Gly Asn Gln Arg Ala His Gly Gln Asp Leu Gly 1475 1480 1485 Thr Leu Gly Ser Cys Leu Gln Arg Phe Thr Thr Met Pro Phe Leu Phe 1490 1495 1500 Cys Asn Val Asn Asp Val Cys Asn Phe Ala Ser Arg Asn Asp Tyr Ser 1505 1510 1515 1520 Tyr Trp Leu Ser Thr Pro Ala Leu Met Pro Met Asn Met Ala Pro Ile 1525 1530 1535 Thr Gly Arg Ala Leu Glu Pro Tyr Ile Ser Arg Cys Thr Val Cys Glu 1540 1545 1550 Gly Pro Ala Ile Ala Ile Ala Val His Ser Gln Thr Thr Asp Ile Pro 1555 1560 1565 Pro Cys Pro His Gly Trp Ile Ser Leu Trp Lys Gly Phe Ser Phe Ile 1570 1575 1580 Met Phe Thr Ser Ala Gly Ser Glu Gly Thr Gly Gln Ala Leu Ala Ser 1585 1590 1595 1600

Pro Gly Ser Cys Leu Glu Glu Phe Arg Ala Ser Pro Phe Leu Glu Cys 1605 1610 1615 His Gly Arg Gly Thr Cys Asn Tyr Tyr Ser Asn Ser Tyr Ser Phe Trp 1620 1625 1630 Leu Ala Ser Leu Asn Pro Glu Arg Met Phe Arg Lys Pro Ile Pro Ser 1635 1640 1645 Thr Val Lys Ala Gly Glu Leu Glu Lys Ile Ile Ser Arg Cys Gln Val 1650 1655 1660 Cys Met Lys Lys Arg His 1665 1670 <210> SEQ ID NO 84 <211> LENGTH: 1712 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 84 Met Gly Arg Asp Gln Arg Ala Val Ala Gly Pro Ala Leu Arg Arg Trp 1 5 10 15 Leu Leu Leu Gly Thr Val Thr Val Gly Phe Leu Ala Gln Ser Val Leu 20 25 30 Ala Gly Val Lys Lys Phe Asp Val Pro Cys Gly Gly Arg Asp Cys Ser 35 40 45 Gly Gly Cys Gln Cys Tyr Pro Glu Lys Gly Gly Arg Gly Gln Pro Gly 50 55 60 Pro Val Gly Pro Gln Gly Tyr Asn Gly Pro Pro Gly Leu Gln Gly Phe 65 70 75 80 Pro Gly Leu Gln Gly Arg Lys Gly Asp Lys Gly Glu Arg Gly Ala Pro 85 90 95 Gly Val Thr Gly Pro Lys Gly Asp Val Gly Ala Arg Gly Val Ser Gly 100 105 110 Phe Pro Gly Ala Asp Gly Ile Pro Gly His Pro Gly Gln Gly Gly Pro 115 120 125 Arg Gly Arg Pro Gly Tyr Asp Gly Cys Asn Gly Thr Gln Gly Asp Ser 130 135 140 Gly Pro Gln Gly Pro Pro Gly Ser Glu Gly Phe Thr Gly Pro Pro Gly 145 150 155 160 Pro Gln Gly Pro Lys Gly Gln Lys Gly Glu Pro Tyr Ala Leu Pro Lys 165 170 175 Glu Glu Arg Asp Arg Tyr Arg Gly Glu Pro Gly Glu Pro Gly Leu Val 180 185 190 Gly Phe Gln Gly Pro Pro Gly Arg Pro Gly His Val Gly Gln Met Gly 195 200 205 Pro Val Gly Ala Pro Gly Arg Pro Gly Pro Pro Gly Pro Pro Gly Pro 210 215 220 Lys Gly Gln Gln Gly Asn Arg Gly Leu Gly Phe Tyr Gly Val Lys Gly 225 230 235 240 Glu Lys Gly Asp Val Gly Gln Pro Gly Pro Asn Gly Ile Pro Ser Asp 245 250 255 Thr Leu His Pro Ile Ile Ala Pro Thr Gly Val Thr Phe His Pro Asp 260 265 270 Gln Tyr Lys Gly Glu Lys Gly Ser Glu Gly Glu Pro Gly Ile Arg Gly 275 280 285 Ile Ser Leu Lys Gly Glu Glu Gly Ile Met Gly Phe Pro Gly Leu Arg 290 295 300 Gly Tyr Pro Gly Leu Ser Gly Glu Lys Gly Ser Pro Gly Gln Lys Gly 305 310 315 320 Ser Arg Gly Leu Asp Gly Tyr Gln Gly Pro Asp Gly Pro Arg Gly Pro 325 330 335 Lys Gly Glu Ala Gly Asp Pro Gly Pro Pro Gly Leu Pro Ala Tyr Ser 340 345 350 Pro His Pro Ser Leu Ala Lys Gly Ala Arg Gly Asp Pro Gly Phe Pro 355 360 365 Gly Ala Gln Gly Glu Pro Gly Ser Gln Gly Glu Pro Gly Asp Pro Gly 370 375 380 Leu Pro Gly Pro Pro Gly Leu Ser Ile Gly Asp Gly Asp Gln Arg Arg 385 390 395 400 Gly Leu Pro Gly Glu Met Gly Pro Lys Gly Phe Ile Gly Asp Pro Gly 405 410 415 Ile Pro Ala Leu Tyr Gly Gly Pro Pro Gly Pro Asp Gly Lys Arg Gly 420 425 430 Pro Pro Gly Pro Pro Gly Leu Pro Gly Pro Pro Gly Pro Asp Gly Phe 435 440 445 Leu Phe Gly Leu Lys Gly Ala Lys Gly Arg Ala Gly Phe Pro Gly Leu 450 455 460 Pro Gly Ser Pro Gly Ala Arg Gly Pro Lys Gly Trp Lys Gly Asp Ala 465 470 475 480 Gly Glu Cys Arg Cys Thr Glu Gly Asp Glu Ala Ile Lys Gly Leu Pro 485 490 495 Gly Leu Pro Gly Pro Lys Gly Phe Ala Gly Ile Asn Gly Glu Pro Gly 500 505 510 Arg Lys Gly Asp Arg Gly Asp Pro Gly Gln His Gly Leu Pro Gly Phe 515 520 525 Pro Gly Leu Lys Gly Val Pro Gly Asn Ile Gly Ala Pro Gly Pro Lys 530 535 540 Gly Ala Lys Gly Asp Ser Arg Thr Ile Thr Thr Lys Gly Glu Arg Gly 545 550 555 560 Gln Pro Gly Val Pro Gly Val Pro Gly Met Lys Gly Asp Asp Gly Ser 565 570 575 Pro Gly Arg Asp Gly Leu Asp Gly Phe Pro Gly Leu Pro Gly Pro Pro 580 585 590 Gly Asp Gly Ile Lys Gly Pro Pro Gly Asp Pro Gly Tyr Pro Gly Ile 595 600 605 Pro Gly Thr Lys Gly Thr Pro Gly Glu Met Gly Pro Pro Gly Leu Gly 610 615 620 Leu Pro Gly Leu Lys Gly Gln Arg Gly Phe Pro Gly Asp Ala Gly Leu 625 630 635 640 Pro Gly Pro Pro Gly Phe Leu Gly Pro Pro Gly Pro Ala Gly Thr Pro 645 650 655 Gly Gln Ile Asp Cys Asp Thr Asp Val Lys Arg Ala Val Gly Gly Asp 660 665 670 Arg Gln Glu Ala Ile Gln Pro Gly Cys Ile Gly Gly Pro Lys Gly Leu 675 680 685 Pro Gly Leu Pro Gly Pro Pro Gly Pro Thr Gly Ala Lys Gly Leu Arg 690 695 700 Gly Ile Pro Gly Phe Ala Gly Ala Asp Gly Gly Pro Gly Pro Arg Gly 705 710 715 720 Leu Pro Gly Asp Ala Gly Arg Glu Gly Phe Pro Gly Pro Pro Gly Phe 725 730 735 Ile Gly Pro Arg Gly Ser Lys Gly Ala Val Gly Leu Pro Gly Pro Asp 740 745 750 Gly Ser Pro Gly Pro Ile Gly Leu Pro Gly Pro Asp Gly Pro Pro Gly 755 760 765 Glu Arg Gly Leu Pro Gly Glu Val Leu Gly Ala Gln Pro Gly Pro Arg 770 775 780 Gly Asp Ala Gly Val Pro Gly Gln Pro Gly Leu Lys Gly Leu Pro Gly 785 790 795 800 Asp Arg Gly Pro Pro Gly Phe Arg Gly Ser Gln Gly Met Pro Gly Met 805 810 815 Pro Gly Leu Lys Gly Gln Pro Gly Leu Pro Gly Pro Ser Gly Gln Pro 820 825 830 Gly Leu Tyr Gly Pro Pro Gly Leu His Gly Phe Pro Gly Ala Pro Gly 835 840 845 Gln Glu Gly Pro Leu Gly Leu Pro Gly Ile Pro Gly Arg Glu Gly Leu 850 855 860 Pro Gly Asp Arg Gly Asp Pro Gly Asp Thr Gly Ala Pro Gly Pro Val 865 870 875 880 Gly Met Lys Gly Leu Ser Gly Asp Arg Gly Asp Ala Gly Phe Thr Gly 885 890 895 Glu Gln Gly His Pro Gly Ser Pro Gly Phe Lys Gly Ile Asp Gly Met 900 905 910 Pro Gly Thr Pro Gly Leu Lys Gly Asp Arg Gly Ser Pro Gly Met Asp 915 920 925 Gly Phe Gln Gly Met Pro Gly Leu Lys Gly Arg Pro Gly Phe Pro Gly 930 935 940 Ser Lys Gly Glu Ala Gly Phe Phe Gly Ile Pro Gly Leu Lys Gly Leu 945 950 955 960 Ala Gly Glu Pro Gly Phe Lys Gly Ser Arg Gly Asp Pro Gly Pro Pro 965 970 975 Gly Pro Pro Pro Val Ile Leu Pro Gly Met Lys Asp Ile Lys Gly Glu 980 985 990 Lys Gly Asp Glu Gly Pro Met Gly Leu Lys Gly Tyr Leu Gly Ala Lys 995 1000 1005 Gly Ile Gln Gly Met Pro Gly Ile Pro Gly Leu Ser Gly Ile Pro Gly 1010 1015 1020 Leu Pro Gly Arg Pro Gly His Ile Lys Gly Val Lys Gly Asp Ile Gly 1025 1030 1035 1040 Val Pro Gly Ile Pro Gly Leu Pro Gly Phe Pro Gly Val Ala Gly Pro 1045 1050 1055 Pro Gly Ile Thr Gly Phe Pro Gly Phe Ile Gly Ser Arg Gly Asp Lys 1060 1065 1070 Gly Ala Pro Gly Arg Ala Gly Leu Tyr Gly Glu Ile Gly Ala Thr Gly 1075 1080 1085 Asp Phe Gly Asp Ile Gly Asp Thr Ile Asn Leu Pro Gly Arg Pro Gly 1090 1095 1100 Leu Lys Gly Glu Arg Gly Thr Thr Gly Ile Pro Gly Leu Lys Gly Phe 1105 1110 1115 1120 Phe Gly Glu Lys Gly Thr Glu Gly Asp Ile Gly Phe Pro Gly Ile Thr 1125 1130 1135 Gly Val Thr Gly Val Gln Gly Pro Pro Gly Leu Lys Gly Gln Thr Gly 1140 1145 1150 Phe Pro Gly Leu Thr Gly Pro Pro Gly Ser Gln Gly Glu Leu Gly Arg 1155 1160 1165 Ile Gly Leu Pro Gly Gly Lys Gly Asp Asp Gly Trp Pro Gly Ala Pro 1170 1175 1180 Gly Leu Pro Gly Phe Pro Gly Leu Arg Gly Ile Arg Gly Leu His Gly 1185 1190 1195 1200 Leu Pro Gly Thr Lys Gly Phe Pro Gly Ser Pro Gly Ser Asp Ile His 1205 1210 1215

Gly Asp Pro Gly Phe Pro Gly Pro Pro Gly Glu Arg Gly Asp Pro Gly 1220 1225 1230 Glu Ala Asn Thr Leu Pro Gly Pro Val Gly Val Pro Gly Gln Lys Gly 1235 1240 1245 Asp Gln Gly Ala Pro Gly Glu Arg Gly Pro Pro Gly Ser Pro Gly Leu 1250 1255 1260 Gln Gly Phe Pro Gly Ile Thr Pro Pro Ser Asn Ile Ser Gly Ala Pro 1265 1270 1275 1280 Gly Asp Lys Gly Ala Pro Gly Ile Phe Gly Leu Lys Gly Tyr Arg Gly 1285 1290 1295 Pro Pro Gly Pro Pro Gly Ser Ala Ala Leu Pro Gly Ser Lys Gly Asp 1300 1305 1310 Thr Gly Asn Pro Gly Ala Pro Gly Thr Pro Gly Thr Lys Gly Trp Ala 1315 1320 1325 Gly Asp Ser Gly Pro Gln Gly Arg Pro Gly Val Phe Gly Leu Pro Gly 1330 1335 1340 Glu Lys Gly Pro Arg Gly Glu Gln Gly Phe Met Gly Asn Thr Gly Pro 1345 1350 1355 1360 Thr Gly Ala Val Gly Asp Arg Gly Pro Lys Gly Pro Lys Gly Asp Pro 1365 1370 1375 Gly Phe Pro Gly Ala Pro Gly Thr Val Gly Ala Pro Gly Ile Ala Gly 1380 1385 1390 Ile Pro Gln Lys Ile Ala Val Gln Pro Gly Thr Val Gly Pro Gln Gly 1395 1400 1405 Arg Arg Gly Pro Pro Gly Ala Pro Gly Glu Met Gly Pro Gln Gly Pro 1410 1415 1420 Pro Gly Glu Pro Gly Phe Arg Gly Ala Pro Gly Lys Ala Gly Pro Gln 1425 1430 1435 1440 Gly Arg Gly Gly Val Ser Ala Val Pro Gly Phe Arg Gly Asp Glu Gly 1445 1450 1455 Pro Ile Gly His Gln Gly Pro Ile Gly Gln Glu Gly Ala Pro Gly Arg 1460 1465 1470 Pro Gly Ser Pro Gly Leu Pro Gly Met Pro Gly Arg Ser Val Ser Ile 1475 1480 1485 Gly Tyr Leu Leu Val Lys His Ser Gln Thr Asp Gln Glu Pro Met Cys 1490 1495 1500 Pro Val Gly Met Asn Lys Leu Trp Ser Gly Tyr Ser Leu Leu Tyr Phe 1505 1510 1515 1520 Glu Gly Gln Glu Lys Ala His Asn Gln Asp Leu Gly Leu Ala Gly Ser 1525 1530 1535 Cys Leu Ala Arg Phe Ser Thr Met Pro Phe Leu Tyr Cys Asn Pro Gly 1540 1545 1550 Asp Val Cys Tyr Tyr Ala Ser Arg Asn Asp Lys Ser Tyr Trp Leu Ser 1555 1560 1565 Thr Thr Ala Pro Leu Pro Met Met Pro Val Ala Glu Asp Glu Ile Lys 1570 1575 1580 Pro Tyr Ile Ser Arg Cys Ser Val Cys Glu Ala Pro Ala Ile Ala Ile 1585 1590 1595 1600 Ala Val His Ser Gln Asp Val Ser Ile Pro His Cys Pro Ala Gly Trp 1605 1610 1615 Arg Ser Leu Trp Ile Gly Tyr Ser Phe Leu Met His Thr Ala Ala Gly 1620 1625 1630 Asp Glu Gly Gly Gly Gln Ser Leu Val Ser Pro Gly Ser Cys Leu Glu 1635 1640 1645 Asp Phe Arg Ala Thr Pro Phe Ile Glu Cys Asn Gly Gly Arg Gly Thr 1650 1655 1660 Cys His Tyr Tyr Ala Asn Lys Tyr Ser Phe Trp Leu Thr Thr Ile Pro 1665 1670 1675 1680 Glu Gln Ser Phe Gln Gly Ser Pro Ser Ala Asp Thr Leu Lys Ala Gly 1685 1690 1695 Leu Ile Arg Thr His Ile Ser Arg Cys Gln Val Cys Met Lys Asn Leu 1700 1705 1710 <210> SEQ ID NO 85 <211> LENGTH: 1427 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 85 Met Ser Met Leu Lys Pro Ser Gly Leu Lys Ala Pro Thr Lys Ile Leu 1 5 10 15 Lys Pro Gly Ser Thr Ala Leu Lys Thr Pro Thr Ala Val Val Ala Pro 20 25 30 Val Glu Lys Thr Ile Ser Ser Glu Lys Ala Ser Ser Thr Pro Ser Ser 35 40 45 Glu Thr Gln Glu Glu Phe Val Asp Asp Phe Arg Val Gly Glu Arg Val 50 55 60 Trp Val Asn Gly Asn Lys Pro Gly Phe Ile Gln Phe Leu Gly Glu Thr 65 70 75 80 Gln Phe Ala Pro Gly Gln Trp Ala Gly Ile Val Leu Asp Glu Pro Ile 85 90 95 Gly Lys Asn Asp Gly Ser Val Ala Gly Val Arg Tyr Phe Gln Cys Glu 100 105 110 Pro Leu Lys Gly Ile Phe Thr Arg Pro Ser Lys Leu Thr Arg Lys Val 115 120 125 Gln Ala Glu Asp Glu Ala Asn Gly Leu Gln Thr Thr Pro Ala Ser Arg 130 135 140 Ala Thr Ser Pro Leu Cys Thr Ser Thr Ala Ser Met Val Ser Ser Ser 145 150 155 160 Pro Ser Thr Pro Ser Asn Ile Pro Gln Lys Pro Ser Gln Pro Ala Ala 165 170 175 Lys Glu Pro Ser Ala Thr Pro Pro Ile Ser Asn Leu Thr Lys Thr Ala 180 185 190 Ser Glu Ser Ile Ser Asn Leu Ser Glu Ala Gly Ser Ile Lys Lys Gly 195 200 205 Glu Arg Glu Leu Lys Ile Gly Asp Arg Val Leu Val Gly Gly Thr Lys 210 215 220 Ala Gly Val Val Arg Phe Leu Gly Glu Thr Asp Phe Ala Lys Gly Glu 225 230 235 240 Trp Cys Gly Val Glu Leu Asp Glu Pro Leu Gly Lys Asn Asp Gly Ala 245 250 255 Val Ala Gly Thr Arg Tyr Phe Gln Cys Gln Pro Lys Tyr Gly Leu Phe 260 265 270 Ala Pro Val His Lys Val Thr Lys Ile Gly Phe Pro Ser Thr Thr Pro 275 280 285 Ala Lys Ala Lys Ala Asn Ala Val Arg Arg Val Met Ala Thr Thr Ser 290 295 300 Ala Ser Leu Lys Arg Ser Pro Ser Ala Ser Ser Leu Ser Ser Met Ser 305 310 315 320 Ser Val Ala Ser Ser Val Ser Ser Arg Pro Ser Arg Thr Gly Leu Leu 325 330 335 Thr Glu Thr Ser Ser Arg Tyr Ala Arg Lys Ile Ser Gly Thr Thr Ala 340 345 350 Leu Gln Glu Ala Leu Lys Glu Lys Gln Gln His Ile Glu Gln Leu Leu 355 360 365 Ala Glu Arg Asp Leu Glu Arg Ala Glu Val Ala Lys Ala Thr Ser His 370 375 380 Val Gly Glu Ile Glu Gln Glu Leu Ala Leu Ala Arg Asp Gly His Asp 385 390 395 400 Gln His Val Leu Glu Leu Glu Ala Lys Met Asp Gln Leu Arg Thr Met 405 410 415 Val Glu Ala Ala Asp Arg Glu Lys Val Glu Leu Leu Asn Gln Leu Glu 420 425 430 Glu Glu Lys Arg Lys Val Glu Asp Leu Gln Phe Arg Val Glu Glu Glu 435 440 445 Ser Ile Thr Lys Gly Asp Leu Glu Thr Gln Thr Lys Leu Glu His Ala 450 455 460 Arg Ile Lys Glu Leu Glu Gln Ser Leu Leu Phe Glu Lys Thr Lys Ala 465 470 475 480 Asp Lys Leu Gln Arg Glu Leu Glu Asp Thr Arg Val Ala Thr Val Ser 485 490 495 Glu Lys Ser Arg Ile Met Glu Leu Glu Lys Asp Leu Ala Leu Arg Val 500 505 510 Gln Glu Val Ala Glu Leu Arg Arg Arg Leu Glu Ser Asn Lys Pro Ala 515 520 525 Gly Asp Val Asp Met Ser Leu Ser Leu Leu Gln Glu Ile Ser Ser Leu 530 535 540 Gln Glu Lys Leu Glu Val Thr Arg Thr Asp His Gln Arg Glu Ile Thr 545 550 555 560 Ser Leu Lys Glu His Phe Gly Ala Arg Glu Glu Thr His Gln Lys Glu 565 570 575 Ile Lys Ala Leu Tyr Thr Ala Thr Glu Lys Leu Ser Lys Glu Asn Glu 580 585 590 Ser Leu Lys Ser Lys Leu Glu His Ala Asn Lys Glu Asn Ser Asp Val 595 600 605 Ile Ala Leu Trp Lys Ser Lys Leu Glu Thr Ala Ile Ala Ser His Gln 610 615 620 Gln Ala Met Glu Glu Leu Lys Val Ser Phe Ser Lys Gly Leu Gly Thr 625 630 635 640 Glu Thr Ala Glu Phe Ala Glu Leu Lys Thr Gln Ile Glu Lys Met Arg 645 650 655 Leu Asp Tyr Gln His Glu Ile Glu Asn Leu Gln Asn Gln Gln Asp Ser 660 665 670 Glu Arg Ala Ala His Ala Lys Glu Met Glu Ala Leu Arg Ala Lys Leu 675 680 685 Met Lys Val Ile Lys Glu Lys Glu Asn Ser Leu Glu Ala Ile Arg Ser 690 695 700 Lys Leu Asp Lys Ala Glu Asp Gln His Leu Val Glu Met Glu Asp Thr 705 710 715 720 Leu Asn Lys Leu Gln Glu Ala Glu Ile Lys Val Lys Glu Leu Glu Val 725 730 735 Leu Gln Ala Lys Cys Asn Glu Gln Thr Lys Val Ile Asp Asn Phe Thr 740 745 750 Ser Gln Leu Lys Ala Thr Glu Glu Lys Leu Leu Asp Leu Asp Ala Leu 755 760 765 Arg Lys Ala Ser Ser Glu Gly Lys Ser Glu Met Lys Lys Leu Arg Gln 770 775 780 Gln Leu Glu Ala Ala Glu Lys Gln Ile Lys His Leu Glu Ile Glu Lys 785 790 795 800

Asn Ala Glu Ser Ser Lys Ala Ser Ser Ile Thr Arg Glu Leu Gln Gly 805 810 815 Arg Glu Leu Lys Leu Thr Asn Leu Gln Glu Asn Leu Ser Glu Val Ser 820 825 830 Gln Val Lys Glu Thr Leu Glu Lys Glu Leu Gln Ile Leu Lys Glu Lys 835 840 845 Phe Ala Glu Ala Ser Glu Glu Ala Val Ser Val Gln Arg Ser Met Gln 850 855 860 Glu Thr Val Asn Lys Leu His Gln Lys Glu Glu Gln Phe Asn Met Leu 865 870 875 880 Ser Ser Asp Leu Glu Lys Leu Arg Glu Asn Leu Ala Asp Met Glu Ala 885 890 895 Lys Phe Arg Glu Lys Asp Glu Arg Glu Glu Gln Leu Ile Lys Ala Lys 900 905 910 Glu Lys Leu Glu Asn Asp Ile Ala Glu Ile Met Lys Met Ser Gly Asp 915 920 925 Asn Ser Ser Gln Leu Thr Lys Met Asn Asp Glu Leu Arg Leu Lys Glu 930 935 940 Arg Asp Val Glu Glu Leu Gln Leu Lys Leu Thr Lys Ala Asn Glu Asn 945 950 955 960 Ala Ser Phe Leu Gln Lys Ser Ile Glu Asp Met Thr Val Lys Ala Glu 965 970 975 Gln Ser Gln Gln Glu Ala Ala Lys Lys His Glu Glu Glu Lys Lys Glu 980 985 990 Leu Glu Arg Lys Leu Ser Asp Leu Glu Lys Lys Met Glu Thr Ser His 995 1000 1005 Asn Gln Cys Gln Glu Leu Lys Ala Arg Tyr Glu Arg Ala Thr Ser Glu 1010 1015 1020 Thr Lys Thr Lys His Glu Glu Ile Leu Gln Asn Leu Gln Lys Thr Leu 1025 1030 1035 1040 Leu Asp Thr Glu Asp Lys Leu Lys Gly Ala Arg Glu Glu Asn Ser Gly 1045 1050 1055 Leu Leu Gln Glu Leu Glu Glu Leu Arg Lys Gln Ala Asp Lys Ala Lys 1060 1065 1070 Ala Ala Gln Thr Ala Glu Asp Ala Met Gln Ile Met Glu Gln Met Thr 1075 1080 1085 Lys Glu Lys Thr Glu Thr Leu Ala Ser Leu Glu Asp Thr Lys Gln Thr 1090 1095 1100 Asn Ala Lys Leu Gln Asn Glu Leu Asp Thr Leu Lys Glu Asn Asn Leu 1105 1110 1115 1120 Lys Asn Val Glu Glu Leu Asn Lys Ser Lys Glu Leu Leu Thr Val Glu 1125 1130 1135 Asn Gln Lys Met Glu Glu Phe Arg Lys Glu Ile Glu Thr Leu Lys Gln 1140 1145 1150 Ala Ala Ala Gln Lys Ser Gln Gln Leu Ser Ala Leu Gln Glu Glu Asn 1155 1160 1165 Val Lys Leu Ala Glu Glu Leu Gly Arg Ser Arg Asp Glu Val Thr Ser 1170 1175 1180 His Gln Lys Leu Glu Glu Glu Arg Ser Val Leu Asn Asn Gln Leu Leu 1185 1190 1195 1200 Glu Met Lys Lys Arg Glu Ser Lys Phe Ile Lys Asp Ala Asp Glu Glu 1205 1210 1215 Lys Ala Ser Leu Gln Lys Ser Ile Ser Ile Thr Ser Ala Leu Leu Thr 1220 1225 1230 Glu Lys Asp Ala Glu Leu Glu Lys Leu Arg Asn Glu Val Thr Val Leu 1235 1240 1245 Arg Gly Glu Asn Ala Ser Ala Lys Ser Leu His Ser Val Val Gln Thr 1250 1255 1260 Leu Glu Ser Asp Lys Val Lys Leu Glu Leu Lys Val Lys Asn Leu Glu 1265 1270 1275 1280 Leu Gln Leu Lys Glu Asn Lys Arg Gln Leu Ser Ser Ser Ser Gly Asn 1285 1290 1295 Thr Asp Thr Gln Ala Asp Glu Asp Glu Arg Ala Gln Glu Ser Gln Ile 1300 1305 1310 Asp Phe Leu Asn Ser Val Ile Val Asp Leu Gln Arg Lys Asn Gln Asp 1315 1320 1325 Leu Lys Met Lys Val Glu Met Met Ser Glu Ala Ala Leu Asn Gly Asn 1330 1335 1340 Gly Asp Asp Leu Asn Asn Tyr Asp Ser Asp Asp Gln Glu Lys Gln Ser 1345 1350 1355 1360 Lys Lys Lys Pro Arg Leu Phe Cys Asp Ile Cys Asp Cys Phe Asp Leu 1365 1370 1375 His Asp Thr Glu Asp Cys Pro Thr Gln Ala Gln Met Ser Glu Asp Pro 1380 1385 1390 Pro His Ser Thr His His Gly Ser Arg Gly Glu Glu Arg Pro Tyr Cys 1395 1400 1405 Glu Ile Cys Glu Met Phe Gly His Trp Ala Thr Asn Cys Asn Asp Asp 1410 1415 1420 Glu Thr Phe 1425 <210> SEQ ID NO 86 <211> LENGTH: 251 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 86 Met Ala Glu Asp Leu Gly Leu Ser Phe Gly Glu Thr Ala Ser Val Glu 1 5 10 15 Met Leu Pro Glu His Gly Ser Cys Arg Pro Lys Ala Arg Ser Ser Ser 20 25 30 Ala Arg Trp Ala Leu Thr Cys Cys Leu Val Leu Leu Pro Phe Leu Ala 35 40 45 Gly Leu Thr Thr Tyr Leu Leu Val Ser Gln Leu Arg Ala Gln Gly Glu 50 55 60 Ala Cys Val Gln Phe Gln Ala Leu Lys Gly Gln Glu Phe Ala Pro Ser 65 70 75 80 His Gln Gln Val Tyr Ala Pro Leu Arg Ala Asp Gly Asp Lys Pro Arg 85 90 95 Ala His Leu Thr Val Val Arg Gln Thr Pro Thr Gln His Phe Lys Asn 100 105 110 Gln Phe Pro Ala Leu His Trp Glu His Glu Leu Gly Leu Ala Phe Thr 115 120 125 Lys Asn Arg Met Asn Tyr Thr Asn Lys Phe Leu Leu Ile Pro Glu Ser 130 135 140 Gly Asp Tyr Phe Ile Tyr Ser Gln Val Thr Phe Arg Gly Met Thr Ser 145 150 155 160 Glu Cys Ser Glu Ile Arg Gln Ala Gly Arg Pro Asn Lys Pro Asp Ser 165 170 175 Ile Thr Val Val Ile Thr Lys Val Thr Asp Ser Tyr Pro Glu Pro Thr 180 185 190 Gln Leu Leu Met Gly Thr Lys Ser Val Cys Glu Val Gly Ser Asn Trp 195 200 205 Phe Gln Pro Ile Tyr Leu Gly Ala Met Phe Ser Leu Gln Glu Gly Asp 210 215 220 Lys Leu Met Val Asn Val Ser Asp Ile Ser Leu Val Asp Tyr Thr Lys 225 230 235 240 Glu Asp Lys Thr Phe Phe Gly Ala Phe Leu Leu 245 250 <210> SEQ ID NO 87 <211> LENGTH: 498 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 87 Met Thr Val Phe Leu Ser Phe Ala Phe Leu Ala Ala Ile Leu Thr His 1 5 10 15 Ile Gly Cys Ser Asn Gln Arg Arg Ser Pro Glu Asn Ser Gly Arg Arg 20 25 30 Tyr Asn Arg Ile Gln His Gly Gln Cys Ala Tyr Thr Phe Ile Leu Pro 35 40 45 Glu His Asp Gly Asn Cys Arg Glu Ser Thr Thr Asp Gln Tyr Asn Thr 50 55 60 Asn Ala Leu Gln Arg Asp Ala Pro His Val Glu Pro Asp Phe Ser Ser 65 70 75 80 Gln Lys Leu Gln His Leu Glu His Val Met Glu Asn Tyr Thr Gln Trp 85 90 95 Leu Gln Lys Leu Glu Asn Tyr Ile Val Glu Asn Met Lys Ser Glu Met 100 105 110 Ala Gln Ile Gln Gln Asn Ala Val Gln Asn His Thr Ala Thr Met Leu 115 120 125 Glu Ile Gly Thr Ser Leu Leu Ser Gln Thr Ala Glu Gln Thr Arg Lys 130 135 140 Leu Thr Asp Val Glu Thr Gln Val Leu Asn Gln Thr Ser Arg Leu Glu 145 150 155 160 Ile Gln Leu Leu Glu Asn Ser Leu Ser Thr Tyr Lys Leu Glu Lys Gln 165 170 175 Leu Leu Gln Gln Thr Asn Glu Ile Leu Lys Ile His Glu Lys Asn Ser 180 185 190 Leu Leu Glu His Lys Ile Leu Glu Met Glu Gly Lys His Lys Glu Glu 195 200 205 Leu Asp Thr Leu Lys Glu Glu Lys Glu Asn Leu Gln Gly Leu Val Thr 210 215 220 Arg Gln Thr Tyr Ile Ile Gln Glu Leu Glu Lys Gln Leu Asn Arg Ala 225 230 235 240 Thr Thr Asn Asn Ser Val Leu Gln Lys Gln Gln Leu Glu Leu Met Asp 245 250 255 Thr Val His Asn Leu Val Asn Leu Cys Thr Lys Glu Gly Val Leu Leu 260 265 270 Lys Gly Gly Lys Arg Glu Glu Glu Lys Pro Phe Arg Asp Cys Ala Asp 275 280 285 Val Tyr Gln Ala Gly Phe Asn Lys Ser Gly Ile Tyr Thr Ile Tyr Ile 290 295 300 Asn Asn Met Pro Glu Pro Lys Lys Val Phe Cys Asn Met Asp Val Asn 305 310 315 320 Gly Gly Gly Trp Thr Val Ile Gln His Arg Glu Asp Gly Ser Leu Asp 325 330 335 Phe Gln Arg Gly Trp Lys Glu Tyr Lys Met Gly Phe Gly Asn Pro Ser 340 345 350 Gly Glu Tyr Trp Leu Gly Asn Glu Phe Ile Phe Ala Ile Thr Ser Gln

355 360 365 Arg Gln Tyr Met Leu Arg Ile Glu Leu Met Asp Trp Glu Gly Asn Arg 370 375 380 Ala Tyr Ser Gln Tyr Asp Arg Phe His Ile Gly Asn Glu Lys Gln Asn 385 390 395 400 Tyr Arg Leu Tyr Leu Lys Gly His Thr Gly Thr Ala Gly Lys Gln Ser 405 410 415 Ser Leu Ile Leu His Gly Ala Asp Phe Ser Thr Lys Asp Ala Asp Asn 420 425 430 Asp Asn Cys Met Cys Lys Cys Ala Leu Met Leu Thr Gly Gly Trp Trp 435 440 445 Phe Asp Ala Cys Gly Pro Ser Asn Leu Asn Gly Met Phe Tyr Thr Ala 450 455 460 Gly Gln Asn His Gly Lys Leu Asn Gly Ile Lys Trp His Tyr Phe Lys 465 470 475 480 Gly Pro Ser Tyr Ser Leu Arg Ser Thr Thr Met Met Ile Arg Pro Leu 485 490 495 Asp Phe <210> SEQ ID NO 88 <211 > LENGTH: 227 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 88 Met Asn Ile Lys Gly Ser Pro Trp Lys Gly Ser Leu Leu Leu Leu Leu 1 5 10 15 Val Ser Asn Leu Leu Leu Cys Gln Ser Val Ala Pro Leu Pro Ile Cys 20 25 30 Pro Gly Gly Ala Ala Arg Cys Gln Val Thr Leu Arg Asp Leu Phe Asp 35 40 45 Arg Ala Val Val Leu Ser His Tyr Ile His Asn Leu Ser Ser Glu Met 50 55 60 Phe Ser Glu Phe Asp Lys Arg Tyr Thr His Gly Arg Gly Phe Ile Thr 65 70 75 80 Lys Ala Ile Asn Ser Cys His Thr Ser Ser Leu Ala Thr Pro Glu Asp 85 90 95 Lys Glu Gln Ala Gln Gln Met Asn Gln Lys Asp Phe Leu Ser Leu Ile 100 105 110 Val Ser Ile Leu Arg Ser Trp Asn Glu Pro Leu Tyr His Leu Val Thr 115 120 125 Glu Val Arg Gly Met Gln Glu Ala Pro Glu Ala Ile Leu Ser Lys Ala 130 135 140 Val Glu Ile Glu Glu Gln Thr Lys Arg Leu Leu Glu Gly Met Glu Leu 145 150 155 160 Ile Val Ser Gln Val His Pro Glu Thr Lys Glu Asn Glu Ile Tyr Pro 165 170 175 Val Trp Ser Gly Leu Pro Ser Leu Gln Met Ala Asp Glu Glu Ser Arg 180 185 190 Leu Ser Ala Tyr Tyr Asn Leu Leu His Cys Leu Arg Arg Asp Ser His 195 200 205 Lys Ile Asp Asn Tyr Leu Lys Leu Leu Lys Cys Arg Ile Ile His Asn 210 215 220 Asn Asn Cys 225 <210> SEQ ID NO 89 <211> LENGTH: 4391 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 89 Met Gly Trp Arg Ala Ala Gly Ala Leu Leu Leu Ala Leu Leu Leu His 1 5 10 15 Gly Arg Leu Leu Ala Val Thr His Gly Leu Arg Ala Tyr Asp Gly Leu 20 25 30 Ser Leu Pro Glu Asp Ile Glu Thr Val Thr Ala Ser Gln Met Arg Trp 35 40 45 Thr His Ser Tyr Leu Ser Asp Asp Glu Asp Met Leu Ala Asp Ser Ile 50 55 60 Ser Gly Asp Asp Leu Gly Ser Gly Asp Leu Gly Ser Gly Asp Phe Gln 65 70 75 80 Met Val Tyr Phe Arg Ala Leu Val Asn Phe Thr Arg Ser Ile Glu Tyr 85 90 95 Ser Pro Gln Leu Glu Asp Ala Gly Ser Arg Glu Phe Arg Glu Val Ser 100 105 110 Glu Ala Val Val Asp Thr Leu Glu Ser Glu Tyr Leu Lys Ile Pro Gly 115 120 125 Asp Gln Val Val Ser Val Val Phe Ile Lys Glu Leu Asp Gly Trp Val 130 135 140 Phe Val Glu Leu Asp Val Gly Ser Glu Gly Asn Ala Asp Gly Ala Gln 145 150 155 160 Ile Gln Glu Met Leu Leu Arg Val Ile Ser Ser Gly Ser Val Ala Ser 165 170 175 Tyr Val Thr Ser Pro Gln Gly Phe Gln Phe Arg Arg Leu Gly Thr Val 180 185 190 Pro Gln Phe Pro Arg Ala Cys Thr Glu Ala Glu Phe Ala Cys His Ser 195 200 205 Tyr Asn Glu Cys Val Ala Leu Glu Tyr Arg Cys Asp Arg Arg Pro Asp 210 215 220 Cys Arg Asp Met Ser Asp Glu Leu Asn Cys Glu Glu Pro Val Leu Gly 225 230 235 240 Ile Ser Pro Thr Phe Ser Leu Leu Val Glu Thr Thr Ser Leu Pro Pro 245 250 255 Arg Pro Glu Thr Thr Ile Met Arg Gln Pro Pro Val Thr His Ala Pro 260 265 270 Gln Pro Leu Leu Pro Gly Ser Val Arg Pro Leu Pro Cys Gly Pro Gln 275 280 285 Glu Ala Ala Cys Arg Asn Gly His Cys Ile Pro Arg Asp Tyr Leu Cys 290 295 300 Asp Gly Gln Glu Asp Cys Glu Asp Gly Ser Asp Glu Leu Asp Cys Gly 305 310 315 320 Pro Pro Pro Pro Cys Glu Pro Asn Glu Phe Pro Cys Gly Asn Gly His 325 330 335 Cys Ala Leu Lys Leu Trp Arg Cys Asp Gly Asp Phe Asp Cys Glu Asp 340 345 350 Arg Thr Asp Glu Ala Asn Cys Pro Thr Lys Arg Pro Glu Glu Val Cys 355 360 365 Gly Pro Thr Gln Phe Arg Cys Val Ser Thr Asn Met Cys Ile Pro Ala 370 375 380 Ser Phe His Cys Asp Glu Glu Ser Asp Cys Pro Asp Arg Ser Asp Glu 385 390 395 400 Phe Gly Cys Met Pro Pro Gln Val Val Thr Pro Pro Arg Glu Ser Ile 405 410 415 Gln Ala Ser Arg Gly Gln Thr Val Thr Phe Thr Cys Val Ala Ile Gly 420 425 430 Val Pro Thr Pro Ile Ile Asn Trp Arg Leu Asn Trp Gly His Ile Pro 435 440 445 Ser His Pro Arg Val Thr Val Thr Ser Glu Gly Gly Arg Gly Thr Leu 450 455 460 Ile Ile Arg Asp Val Lys Glu Ser Asp Gln Gly Ala Tyr Thr Cys Glu 465 470 475 480 Ala Met Asn Ala Arg Gly Met Val Phe Gly Ile Pro Asp Gly Val Leu 485 490 495 Glu Leu Val Pro Gln Arg Gly Pro Cys Pro Asp Gly His Phe Tyr Leu 500 505 510 Glu His Ser Ala Ala Cys Leu Pro Cys Phe Cys Phe Gly Ile Thr Ser 515 520 525 Val Cys Gln Ser Thr Arg Arg Phe Arg Asp Gln Ile Arg Leu Arg Phe 530 535 540 Asp Gln Pro Asp Asp Phe Lys Gly Val Asn Val Thr Met Pro Ala Gln 545 550 555 560 Pro Gly Thr Pro Pro Leu Ser Ser Thr Gln Leu Gln Ile Asp Pro Ser 565 570 575 Leu His Glu Phe Gln Leu Val Asp Leu Ser Arg Arg Phe Leu Val His 580 585 590 Asp Ser Phe Trp Ala Leu Pro Glu Gln Phe Leu Gly Asn Lys Val Asp 595 600 605 Ser Tyr Gly Gly Ser Leu Arg Tyr Asn Val Arg Tyr Glu Leu Ala Arg 610 615 620 Gly Met Leu Glu Pro Val Gln Arg Pro Asp Val Val Leu Met Gly Ala 625 630 635 640 Gly Tyr Arg Leu Leu Ser Arg Gly His Thr Pro Thr Gln Pro Gly Ala 645 650 655 Leu Asn Gln Arg Gln Val Gln Phe Ser Glu Glu His Trp Val His Glu 660 665 670 Ser Gly Arg Pro Val Gln Arg Ala Glu Leu Leu Gln Val Leu Gln Ser 675 680 685 Leu Glu Ala Val Leu Ile Gln Thr Val Tyr Asn Thr Lys Met Ala Ser 690 695 700 Val Gly Leu Ser Asp Ile Ala Met Asp Thr Thr Val Thr His Ala Thr 705 710 715 720 Ser His Gly Arg Ala His Ser Val Glu Glu Cys Arg Cys Pro Ile Gly 725 730 735 Tyr Ser Gly Leu Ser Cys Glu Ser Cys Asp Ala His Phe Thr Arg Val 740 745 750 Pro Gly Gly Pro Tyr Leu Gly Thr Cys Ser Gly Cys Asn Cys Asn Gly 755 760 765 His Ala Ser Ser Cys Asp Pro Val Tyr Gly His Cys Leu Asn Cys Gln 770 775 780 His Asn Thr Glu Gly Pro Gln Cys Asn Lys Cys Lys Ala Gly Phe Phe 785 790 795 800 Gly Asp Ala Met Lys Ala Thr Ala Thr Ser Cys Arg Pro Cys Pro Cys 805 810 815 Pro Tyr Ile Asp Ala Ser Arg Arg Phe Ser Asp Thr Cys Phe Leu Asp 820 825 830 Thr Asp Gly Gln Ala Thr Cys Asp Ala Cys Ala Pro Gly Tyr Thr Gly 835 840 845 Arg Arg Cys Glu Ser Cys Ala Pro Gly Tyr Glu Gly Asn Pro Ile Gln 850 855 860 Pro Gly Gly Lys Cys Arg Pro Val Asn Gln Glu Ile Val Arg Cys Asp 865 870 875 880

Glu Arg Gly Ser Met Gly Thr Ser Gly Glu Ala Cys Arg Cys Lys Asn 885 890 895 Asn Val Val Gly Arg Leu Cys Asn Glu Cys Ala Asp Gly Ser Phe His 900 905 910 Leu Ser Thr Arg Asn Pro Asp Gly Cys Leu Lys Cys Phe Cys Met Gly 915 920 925 Val Ser Arg His Cys Thr Ser Ser Ser Trp Ser Arg Ala Gln Leu His 930 935 940 Gly Ala Ser Glu Glu Pro Gly His Phe Ser Leu Thr Asn Ala Ala Ser 945 950 955 960 Thr His Thr Thr Asn Glu Gly Ile Phe Ser Pro Thr Pro Gly Glu Leu 965 970 975 Gly Phe Ser Ser Phe His Arg Leu Leu Ser Gly Pro Tyr Phe Trp Ser 980 985 990 Leu Pro Ser Arg Phe Leu Gly Asp Lys Val Thr Ser Tyr Gly Gly Glu 995 1000 1005 Leu Arg Phe Thr Val Thr Gln Arg Ser Gln Pro Gly Ser Thr Pro Leu 1010 1015 1020 His Gly Gln Pro Leu Val Val Leu Gln Gly Asn Asn Ile Ile Leu Glu 1025 1030 1035 1040 His His Val Ala Gln Glu Pro Ser Pro Gly Gln Pro Ser Thr Phe Ile 1045 1050 1055 Val Pro Phe Arg Glu Gln Ala Trp Gln Arg Pro Asp Gly Gln Pro Ala 1060 1065 1070 Thr Arg Glu His Leu Leu Met Ala Leu Ala Gly Ile Asp Thr Leu Leu 1075 1080 1085 Ile Arg Ala Ser Tyr Ala Gln Gln Pro Ala Glu Ser Arg Val Ser Gly 1090 1095 1100 Ile Ser Met Asp Val Ala Val Pro Glu Glu Thr Gly Gln Asp Pro Ala 1105 1110 1115 1120 Leu Glu Val Glu Gln Cys Ser Cys Pro Pro Gly Tyr Arg Gly Pro Ser 1125 1130 1135 Cys Gln Asp Cys Asp Thr Gly Tyr Thr Arg Thr Pro Ser Gly Leu Tyr 1140 1145 1150 Leu Gly Thr Cys Glu Arg Cys Ser Cys His Gly His Ser Glu Ala Cys 1155 1160 1165 Glu Pro Glu Thr Gly Ala Cys Gln Gly Cys Gln His His Thr Glu Gly 1170 1175 1180 Pro Arg Cys Glu Gln Cys Gln Pro Gly Tyr Tyr Gly Asp Ala Gln Arg 1185 1190 1195 1200 Gly Thr Pro Gln Asp Cys Gln Leu Cys Pro Cys Tyr Gly Asp Pro Ala 1205 1210 1215 Ala Gly Gln Ala Ala His Thr Cys Phe Leu Asp Thr Asp Gly His Pro 1220 1225 1230 Thr Cys Asp Ala Cys Ser Pro Gly His Ser Gly Arg His Cys Glu Arg 1235 1240 1245 Cys Ala Pro Gly Tyr Tyr Gly Asn Pro Ser Gln Gly Gln Pro Cys Gln 1250 1255 1260 Arg Asp Ser Gln Val Pro Gly Pro Ile Gly Cys Asn Cys Asp Pro Gln 1265 1270 1275 1280 Gly Ser Val Ser Ser Gln Cys Asp Ala Ala Gly Gln Cys Gln Cys Lys 1285 1290 1295 Ala Gln Val Glu Gly Leu Thr Cys Ser His Cys Arg Pro His His Phe 1300 1305 1310 His Leu Ser Ala Ser Asn Pro Asp Gly Cys Leu Pro Cys Phe Cys Met 1315 1320 1325 Gly Ile Thr Gln Gln Cys Ala Ser Ser Ala Tyr Thr Arg His Leu Ile 1330 1335 1340 Ser Thr His Phe Ala Pro Gly Asp Phe Gln Gly Phe Ala Leu Val Asn 1345 1350 1355 1360 Pro Gln Arg Asn Ser Arg Leu Thr Gly Glu Phe Thr Val Glu Pro Val 1365 1370 1375 Pro Glu Gly Ala Gln Leu Ser Phe Gly Asn Phe Ala Gln Leu Gly His 1380 1385 1390 Glu Ser Phe Tyr Trp Gln Leu Pro Glu Thr Tyr Gln Gly Asp Lys Val 1395 1400 1405 Ala Ala Tyr Gly Gly Lys Leu Arg Tyr Thr Leu Ser Tyr Thr Ala Gly 1410 1415 1420 Pro Gln Gly Ser Pro Leu Ser Asp Pro Asp Val Gln Ile Thr Gly Asn 1425 1430 1435 1440 Asn Ile Met Leu Val Ala Ser Gln Pro Ala Leu Gln Gly Pro Glu Arg 1445 1450 1455 Arg Ser Tyr Glu Ile Met Phe Arg Glu Glu Phe Trp Arg Arg Pro Asp 1460 1465 1470 Gly Gln Pro Ala Thr Arg Glu His Leu Leu Met Ala Leu Ala Asp Leu 1475 1480 1485 Asp Glu Leu Leu Ile Arg Ala Thr Phe Ser Ser Val Pro Leu Ala Ala 1490 1495 1500 Ser Ile Ser Ala Val Ser Leu Glu Val Ala Gln Pro Gly Pro Ser Asn 1505 1510 1515 1520 Arg Pro Arg Ala Leu Glu Val Glu Glu Cys Arg Cys Pro Pro Gly Tyr 1525 1530 1535 Ile Gly Leu Ser Cys Gln Asp Cys Ala Pro Gly Tyr Thr Arg Thr Gly 1540 1545 1550 Ser Gly Leu Tyr Leu Gly His Cys Glu Leu Cys Glu Cys Asn Gly His 1555 1560 1565 Ser Asp Leu Cys His Pro Glu Thr Gly Ala Cys Ser Gln Cys Gln His 1570 1575 1580 Asn Ala Ala Gly Glu Phe Cys Glu Leu Cys Ala Pro Gly Tyr Tyr Gly 1585 1590 1595 1600 Asp Ala Thr Ala Gly Thr Pro Glu Asp Cys Gln Pro Cys Ala Cys Pro 1605 1610 1615 Leu Thr Asn Pro Glu Asn Met Phe Ser Arg Thr Cys Glu Ser Leu Gly 1620 1625 1630 Ala Gly Gly Tyr Arg Cys Thr Ala Cys Glu Pro Gly Tyr Thr Gly Gln 1635 1640 1645 Tyr Cys Glu Gln Cys Gly Pro Gly Tyr Val Gly Asn Pro Ser Val Gln 1650 1655 1660 Gly Gly Gln Cys Leu Pro Glu Thr Asn Gln Ala Pro Leu Val Val Glu 1665 1670 1675 1680 Val His Pro Ala Arg Ser Ile Val Pro Gln Gly Gly Ser His Ser Leu 1685 1690 1695 Arg Cys Gln Val Ser Gly Ser Pro Pro His Tyr Phe Tyr Trp Ser Arg 1700 1705 1710 Glu Asp Gly Arg Pro Val Pro Ser Gly Thr Gln Gln Arg His Gln Gly 1715 1720 1725 Ser Glu Leu His Phe Pro Ser Val Gln Pro Ser Asp Ala Gly Val Tyr 1730 1735 1740 Ile Cys Thr Cys Arg Asn Leu His Gln Ser Asn Thr Ser Arg Ala Glu 1745 1750 1755 1760 Leu Leu Val Thr Glu Ala Pro Ser Lys Pro Ile Thr Val Thr Val Glu 1765 1770 1775 Glu Gln Arg Ser Gln Ser Val Arg Pro Gly Ala Asp Val Thr Phe Ile 1780 1785 1790 Cys Thr Ala Lys Ser Lys Ser Pro Ala Tyr Thr Leu Val Trp Thr Arg 1795 1800 1805 Leu His Asn Gly Lys Leu Pro Thr Arg Ala Met Asp Phe Asn Gly Ile 1810 1815 1820 Leu Thr Ile Arg Asn Val Gln Leu Ser Asp Ala Gly Thr Tyr Val Cys 1825 1830 1835 1840 Thr Gly Ser Asn Met Phe Ala Met Asp Gln Gly Thr Ala Thr Leu His 1845 1850 1855 Val Gln Ala Ser Gly Thr Leu Ser Ala Pro Val Val Ser Ile His Pro 1860 1865 1870 Pro Gln Leu Thr Val Gln Pro Gly Gln Leu Ala Glu Phe Arg Cys Ser 1875 1880 1885 Ala Thr Gly Ser Pro Thr Pro Thr Leu Glu Trp Thr Gly Gly Pro Gly 1890 1895 1900 Gly Gln Leu Pro Ala Lys Ala Gln Ile His Gly Gly Ile Leu Arg Leu 1905 1910 1915 1920 Pro Ala Val Glu Pro Thr Asp Gln Ala Gln Tyr Leu Cys Arg Ala His 1925 1930 1935 Ser Ser Ala Gly Gln Gln Val Ala Arg Ala Val Leu His Val His Gly 1940 1945 1950 Gly Gly Gly Pro Arg Val Gln Val Ser Pro Glu Arg Thr Gln Val His 1955 1960 1965 Ala Gly Arg Thr Val Arg Leu Tyr Cys Arg Ala Ala Gly Val Pro Ser 1970 1975 1980 Ala Thr Ile Thr Trp Arg Lys Glu Gly Gly Ser Leu Pro Pro Gln Ala 1985 1990 1995 2000 Arg Ser Glu Arg Thr Asp Ile Ala Thr Leu Leu Ile Pro Ala Ile Thr 2005 2010 2015 Thr Ala Asp Ala Gly Phe Tyr Leu Cys Val Ala Thr Ser Pro Ala Gly 2020 2025 2030 Thr Ala Gln Ala Arg Ile Gln Val Val Val Leu Ser Ala Ser Asp Ala 2035 2040 2045 Ser Pro Pro Pro Val Lys Ile Glu Ser Ser Ser Pro Ser Val Thr Glu 2050 2055 2060 Gly Gln Thr Leu Asp Leu Asn Cys Val Val Ala Gly Ser Ala His Ala 2065 2070 2075 2080 Gln Val Thr Trp Tyr Arg Arg Gly Gly Ser Leu Pro Pro His Thr Gln 2085 2090 2095 Val His Gly Ser Arg Leu Arg Leu Pro Gln Val Ser Pro Ala Asp Ser 2100 2105 2110 Gly Glu Tyr Val Cys Arg Val Glu Asn Gly Ser Gly Pro Lys Glu Ala 2115 2120 2125 Ser Ile Thr Val Ser Val Leu His Gly Thr His Ser Gly Pro Ser Tyr 2130 2135 2140 Thr Pro Val Pro Gly Ser Thr Arg Pro Ile Arg Ile Glu Pro Ser Ser 2145 2150 2155 2160 Ser His Val Ala Glu Gly Gln Thr Leu Asp Leu Asn Cys Val Val Pro 2165 2170 2175 Gly Gln Ala His Ala Gln Val Thr Trp His Lys Arg Gly Gly Ser Leu 2180 2185 2190 Pro Ala Arg His Gln Thr His Gly Ser Leu Leu Arg Leu His Gln Val 2195 2200 2205 Thr Pro Ala Asp Ser Gly Glu Tyr Val Cys His Val Val Gly Thr Ser

2210 2215 2220 Gly Pro Leu Glu Ala Ser Val Leu Val Thr Ile Glu Ala Ser Val Ile 2225 2230 2235 2240 Pro Gly Pro Ile Pro Pro Val Arg Ile Glu Ser Ser Ser Ser Thr Val 2245 2250 2255 Ala Glu Gly Gln Thr Leu Asp Leu Ser Cys Val Val Ala Gly Gln Ala 2260 2265 2270 His Ala Gln Val Thr Trp Tyr Lys Arg Gly Gly Ser Leu Pro Ala Arg 2275 2280 2285 His Gln Val Arg Gly Ser Arg Leu Tyr Ile Phe Gln Ala Ser Pro Ala 2290 2295 2300 Asp Ala Gly Gln Tyr Val Cys Arg Ala Ser Asn Gly Met Glu Ala Ser 2305 2310 2315 2320 Ile Thr Val Thr Val Thr Gly Thr Gln Gly Ala Asn Leu Ala Tyr Pro 2325 2330 2335 Ala Gly Ser Thr Gln Pro Ile Arg Ile Glu Pro Ser Ser Ser Gln Val 2340 2345 2350 Ala Glu Gly Gln Thr Leu Asp Leu Asn Cys Val Val Pro Gly Gln Ser 2355 2360 2365 His Ala Gln Val Thr Trp His Lys Arg Gly Gly Ser Leu Pro Val Arg 2370 2375 2380 His Gln Thr His Gly Ser Leu Leu Arg Leu Tyr Gln Ala Ser Pro Ala 2385 2390 2395 2400 Asp Ser Gly Glu Tyr Val Cys Arg Val Leu Gly Ser Ser Val Pro Leu 2405 2410 2415 Glu Ala Ser Val Leu Val Thr Ile Glu Pro Ala Gly Ser Val Pro Ala 2420 2425 2430 Leu Gly Val Thr Pro Thr Val Arg Ile Glu Ser Ser Ser Ser Gln Val 2435 2440 2445 Ala Glu Gly Gln Thr Leu Asp Leu Asn Cys Leu Val Ala Gly Gln Ala 2450 2455 2460 His Ala Gln Val Thr Trp His Lys Arg Gly Gly Ser Leu Pro Ala Arg 2465 2470 2475 2480 His Gln Val His Gly Ser Arg Leu Arg Leu Leu Gln Val Thr Pro Ala 2485 2490 2495 Asp Ser Gly Glu Tyr Val Cys Arg Val Val Gly Ser Ser Gly Thr Gln 2500 2505 2510 Glu Ala Ser Val Leu Val Thr Ile Gln Gln Arg Leu Ser Gly Ser His 2515 2520 2525 Ser Gln Gly Val Ala Tyr Pro Val Arg Ile Glu Ser Ser Ser Ala Ser 2530 2535 2540 Leu Ala Asn Gly His Thr Leu Asp Leu Asn Cys Leu Val Ala Ser Gln 2545 2550 2555 2560 Ala Pro His Thr Ile Thr Trp Tyr Lys Arg Gly Gly Ser Leu Pro Ser 2565 2570 2575 Arg His Gln Ile Val Gly Ser Arg Leu Arg Ile Pro Gln Val Thr Pro 2580 2585 2590 Ala Asp Ser Gly Glu Tyr Val Cys His Val Ser Asn Gly Ala Gly Ser 2595 2600 2605 Arg Glu Thr Ser Leu Ile Val Thr Ile Gln Gly Ser Gly Ser Ser His 2610 2615 2620 Val Pro Ser Val Ser Pro Pro Ile Arg Ile Glu Ser Ser Ser Pro Thr 2625 2630 2635 2640 Val Val Glu Gly Gln Thr Leu Asp Leu Asn Cys Val Val Ala Arg Gln 2645 2650 2655 Pro Gln Ala Ile Ile Thr Trp Tyr Lys Arg Gly Gly Ser Leu Pro Ser 2660 2665 2670 Arg His Gln Thr His Gly Ser His Leu Arg Leu His Gln Met Ser Val 2675 2680 2685 Ala Asp Ser Gly Glu Tyr Val Cys Arg Ala Asn Asn Asn Ile Asp Ala 2690 2695 2700 Leu Glu Ala Ser Ile Val Ile Ser Val Ser Pro Ser Ala Gly Ser Pro 2705 2710 2715 2720 Ser Ala Pro Gly Ser Ser Met Pro Ile Arg Ile Glu Ser Ser Ser Ser 2725 2730 2735 His Val Ala Glu Gly Glu Thr Leu Asp Leu Asn Cys Val Val Pro Gly 2740 2745 2750 Gln Ala His Ala Gln Val Thr Trp His Lys Arg Gly Gly Ser Leu Pro 2755 2760 2765 Ser His His Gln Thr Arg Gly Ser Arg Leu Arg Leu His His Val Ser 2770 2775 2780 Pro Ala Asp Ser Gly Glu Tyr Val Cys Arg Val Met Gly Ser Ser Gly 2785 2790 2795 2800 Pro Leu Glu Ala Ser Val Leu Val Thr Ile Glu Ala Ser Gly Ser Ser 2805 2810 2815 Ala Val His Val Pro Ala Pro Gly Gly Ala Pro Pro Ile Arg Ile Glu 2820 2825 2830 Pro Ser Ser Ser Arg Val Ala Glu Gly Gln Thr Leu Asp Leu Lys Cys 2835 2840 2845 Val Val Pro Gly Gln Ala His Ala Gln Val Thr Trp His Lys Arg Gly 2850 2855 2860 Gly Asn Leu Pro Ala Arg His Gln Val His Gly Pro Leu Leu Arg Leu 2865 2870 2875 2880 Asn Gln Val Ser Pro Ala Asp Ser Gly Glu Tyr Ser Cys Gln Val Thr 2885 2890 2895 Gly Ser Ser Gly Thr Leu Glu Ala Ser Val Leu Val Thr Ile Glu Pro 2900 2905 2910 Ser Ser Pro Gly Pro Ile Pro Ala Pro Gly Leu Ala Gln Pro Ile Tyr 2915 2920 2925 Ile Glu Ala Ser Ser Ser His Val Thr Glu Gly Gln Thr Leu Asp Leu 2930 2935 2940 Asn Cys Val Val Pro Gly Gln Ala His Ala Gln Val Thr Trp Tyr Lys 2945 2950 2955 2960 Arg Gly Gly Ser Leu Pro Ala Arg His Gln Thr His Gly Ser Gln Leu 2965 2970 2975 Arg Leu His Leu Val Ser Pro Ala Asp Ser Gly Glu Tyr Val Cys Arg 2980 2985 2990 Ala Ala Ser Gly Pro Gly Pro Glu Gln Glu Ala Ser Phe Thr Val Thr 2995 3000 3005 Val Pro Pro Ser Glu Gly Ser Ser Tyr Arg Leu Arg Ser Pro Val Ile 3010 3015 3020 Ser Ile Asp Pro Pro Ser Ser Thr Val Gln Gln Gly Gln Asp Ala Ser 3025 3030 3035 3040 Phe Lys Cys Leu Ile His Asp Gly Ala Ala Pro Ile Ser Leu Glu Trp 3045 3050 3055 Lys Thr Arg Asn Gln Glu Leu Glu Asp Asn Val His Ile Ser Pro Asn 3060 3065 3070 Gly Ser Ile Ile Thr Ile Val Gly Thr Arg Pro Ser Asn His Gly Thr 3075 3080 3085 Tyr Arg Cys Val Ala Ser Asn Ala Tyr Gly Val Ala Gln Ser Val Val 3090 3095 3100 Asn Leu Ser Val His Gly Pro Pro Thr Val Ser Val Leu Pro Glu Gly 3105 3110 3115 3120 Pro Val Trp Val Lys Val Gly Lys Ala Val Thr Leu Glu Cys Val Ser 3125 3130 3135 Ala Gly Glu Pro Arg Ser Ser Ala Arg Trp Thr Arg Ile Ser Ser Thr 3140 3145 3150 Pro Ala Lys Leu Glu Gln Arg Thr Tyr Gly Leu Met Asp Ser His Ala 3155 3160 3165 Val Leu Gln Ile Ser Ser Ala Lys Pro Ser Asp Ala Gly Thr Tyr Val 3170 3175 3180 Cys Leu Ala Gln Asn Ala Leu Gly Thr Ala Gln Lys Gln Val Glu Val 3185 3190 3195 3200 Ile Val Asp Thr Gly Ala Met Ala Pro Gly Ala Pro Gln Val Gln Ala 3205 3210 3215 Glu Glu Ala Glu Leu Thr Val Glu Ala Gly His Thr Ala Thr Leu Arg 3220 3225 3230 Cys Ser Ala Thr Gly Ser Pro Ala Pro Thr Ile His Trp Ser Lys Leu 3235 3240 3245 Arg Ser Pro Leu Pro Trp Gln His Arg Leu Glu Gly Asp Thr Leu Ile 3250 3255 3260 Ile Pro Arg Val Ala Gln Gln Asp Ser Gly Gln Tyr Ile Cys Asn Ala 3265 3270 3275 3280 Thr Ser Pro Ala Gly His Ala Glu Ala Thr Ile Ile Leu His Val Glu 3285 3290 3295 Ser Pro Pro Tyr Ala Thr Thr Val Pro Glu His Ala Ser Val Gln Ala 3300 3305 3310 Gly Glu Thr Val Gln Leu Gln Cys Leu Ala His Gly Thr Pro Pro Leu 3315 3320 3325 Thr Phe Gln Trp Ser Arg Val Gly Ser Ser Leu Pro Gly Arg Ala Thr 3330 3335 3340 Ala Arg Asn Glu Leu Leu His Phe Glu Arg Ala Ala Pro Glu Asp Ser 3345 3350 3355 3360 Gly Arg Tyr Arg Cys Arg Val Thr Asn Lys Val Gly Ser Ala Glu Ala 3365 3370 3375 Phe Ala Gln Leu Leu Val Gln Gly Pro Pro Gly Ser Leu Pro Ala Thr 3380 3385 3390 Ser Ile Pro Ala Gly Ser Thr Pro Thr Val Gln Val Thr Pro Gln Leu 3395 3400 3405 Glu Thr Lys Ser Ile Gly Ala Ser Val Glu Phe His Cys Ala Val Pro 3410 3415 3420 Ser Asp Arg Gly Thr Gln Leu Arg Trp Phe Lys Glu Gly Gly Gln Leu 3425 3430 3435 3440 Pro Pro Gly His Ser Val Gln Asp Gly Val Leu Arg Ile Gln Asn Leu 3445 3450 3455 Asp Gln Ser Cys Gln Gly Thr Tyr Ile Cys Gln Ala His Gly Pro Trp 3460 3465 3470 Gly Lys Ala Gln Ala Ser Ala Gln Leu Val Ile Gln Ala Leu Pro Ser 3475 3480 3485 Val Leu Ile Asn Ile Arg Thr Ser Val Gln Thr Val Val Val Gly His 3490 3495 3500 Ala Val Glu Phe Glu Cys Leu Ala Leu Gly Asp Pro Lys Pro Gln Val 3505 3510 3515 3520 Thr Trp Ser Lys Val Gly Gly His Leu Arg Pro Gly Ile Val Gln Ser 3525 3530 3535 Gly Gly Val Val Arg Ile Ala His Val Glu Leu Ala Asp Ala Gly Gln 3540 3545 3550

Tyr Arg Cys Thr Ala Thr Asn Ala Ala Gly Thr Thr Gln Ser His Val 3555 3560 3565 Leu Leu Leu Val Gln Ala Leu Pro Gln Ile Ser Met Pro Gln Glu Val 3570 3575 3580 Arg Val Pro Ala Gly Ser Ala Ala Val Phe Pro Cys Ile Ala Ser Gly 3585 3590 3595 3600 Tyr Pro Thr Pro Asp Ile Ser Trp Ser Lys Leu Asp Gly Ser Leu Pro 3605 3610 3615 Pro Asp Ser Arg Leu Glu Asn Asn Met Leu Met Leu Pro Ser Val Arg 3620 3625 3630 Pro Gln Asp Ala Gly Thr Tyr Val Cys Thr Ala Thr Asn Arg Gln Gly 3635 3640 3645 Lys Val Lys Ala Phe Ala His Leu Gln Val Pro Glu Arg Val Val Pro 3650 3655 3660 Tyr Phe Thr Gln Thr Pro Tyr Ser Phe Leu Pro Leu Pro Thr Ile Lys 3665 3670 3675 3680 Asp Ala Tyr Arg Lys Phe Glu Ile Lys Ile Thr Phe Arg Pro Asp Ser 3685 3690 3695 Ala Asp Gly Met Leu Leu Tyr Asn Gly Gln Lys Arg Val Pro Gly Ser 3700 3705 3710 Pro Thr Asn Leu Ala Asn Arg Gln Pro Asp Phe Ile Ser Phe Gly Leu 3715 3720 3725 Val Gly Gly Arg Pro Glu Phe Arg Phe Asp Ala Gly Ser Gly Met Ala 3730 3735 3740 Thr Ile Arg His Pro Thr Pro Leu Ala Leu Gly His Phe His Thr Val 3745 3750 3755 3760 Thr Leu Leu Arg Ser Leu Thr Gln Gly Ser Leu Ile Val Gly Asp Leu 3765 3770 3775 Ala Pro Val Asn Gly Thr Ser Gln Gly Lys Phe Gln Gly Leu Asp Leu 3780 3785 3790 Asn Glu Glu Leu Tyr Leu Gly Gly Tyr Pro Asp Tyr Gly Ala Ile Pro 3795 3800 3805 Lys Ala Gly Leu Ser Ser Gly Phe Ile Gly Cys Val Arg Glu Leu Arg 3810 3815 3820 Ile Gln Gly Glu Glu Ile Val Phe His Asp Leu Asn Leu Thr Ala His 3825 3830 3835 3840 Gly Ile Ser His Cys Pro Thr Cys Arg Asp Arg Pro Cys Gln Asn Gly 3845 3850 3855 Gly Gln Cys His Asp Ser Glu Ser Ser Ser Tyr Val Cys Val Cys Pro 3860 3865 3870 Ala Gly Phe Thr Gly Ser Arg Cys Glu His Ser Gln Ala Leu His Cys 3875 3880 3885 His Pro Glu Ala Cys Gly Pro Asp Ala Thr Cys Val Asn Arg Pro Asp 3890 3895 3900 Gly Arg Gly Tyr Thr Cys Arg Cys His Leu Gly Arg Ser Gly Leu Arg 3905 3910 3915 3920 Cys Glu Glu Gly Val Thr Val Thr Thr Pro Ser Leu Ser Gly Ala Gly 3925 3930 3935 Ser Tyr Leu Ala Leu Pro Ala Leu Thr Asn Thr His His Glu Leu Arg 3940 3945 3950 Leu Asp Val Glu Phe Lys Pro Leu Ala Pro Asp Gly Val Leu Leu Phe 3955 3960 3965 Ser Gly Gly Lys Ser Gly Pro Val Glu Asp Phe Val Ser Leu Ala Met 3970 3975 3980 Val Gly Gly His Leu Glu Phe Arg Tyr Glu Leu Gly Ser Gly Leu Ala 3985 3990 3995 4000 Val Leu Arg Ser Ala Glu Pro Leu Ala Leu Gly Arg Trp His Arg Val 4005 4010 4015 Ser Ala Glu Arg Leu Asn Lys Asp Gly Ser Leu Arg Val Asn Gly Gly 4020 4025 4030 Arg Pro Val Leu Arg Ser Ser Pro Gly Lys Ser Gln Gly Leu Asn Leu 4035 4040 4045 His Thr Leu Leu Tyr Leu Gly Gly Val Glu Pro Ser Val Pro Leu Ser 4050 4055 4060 Pro Ala Thr Asn Met Ser Ala His Phe Arg Gly Cys Val Gly Glu Val 4065 4070 4075 4080 Ser Val Asn Gly Lys Arg Leu Asp Leu Thr Tyr Ser Phe Leu Gly Ser 4085 4090 4095 Gln Gly Ile Gly Gln Cys Tyr Asp Ser Ser Pro Cys Glu Arg Gln Pro 4100 4105 4110 Cys Gln His Gly Ala Thr Cys Met Pro Ala Gly Glu Tyr Glu Phe Gln 4115 4120 4125 Cys Leu Cys Arg Asp Gly Phe Lys Gly Asp Leu Cys Glu His Glu Glu 4130 4135 4140 Asn Pro Cys Gln Leu Arg Glu Pro Cys Leu His Gly Gly Thr Cys Gln 4145 4150 4155 4160 Gly Thr Arg Cys Leu Cys Leu Pro Gly Phe Ser Gly Pro Arg Cys Gln 4165 4170 4175 Gln Gly Ser Gly His Gly Ile Ala Glu Ser Asp Trp His Leu Glu Gly 4180 4185 4190 Ser Gly Gly Asn Asp Ala Pro Gly Gln Tyr Gly Ala Tyr Phe His Asp 4195 4200 4205 Asp Gly Phe Leu Ala Phe Pro Gly His Val Phe Ser Arg Ser Leu Pro 4210 4215 4220 Glu Val Pro Glu Thr Ile Glu Leu Glu Val Arg Thr Ser Thr Ala Ser 4225 4230 4235 4240 Gly Leu Leu Leu Trp Gln Gly Val Glu Val Gly Glu Ala Gly Gln Gly 4245 4250 4255 Lys Asp Phe Ile Ser Leu Gly Leu Gln Asp Gly His Leu Val Phe Arg 4260 4265 4270 Tyr Gln Leu Gly Ser Gly Glu Ala Arg Leu Val Ser Glu Asp Pro Ile 4275 4280 4285 Asn Asp Gly Glu Trp His Arg Val Thr Ala Leu Arg Glu Gly Arg Arg 4290 4295 4300 Gly Ser Ile Gln Val Asp Gly Glu Glu Leu Val Ser Gly Arg Ser Pro 4305 4310 4315 4320 Gly Pro Asn Val Ala Val Asn Ala Lys Gly Ser Val Tyr Ile Gly Gly 4325 4330 4335 Ala Pro Asp Val Ala Thr Leu Thr Gly Gly Arg Phe Ser Ser Gly Ile 4340 4345 4350 Thr Gly Cys Val Lys Asn Leu Val Leu His Ser Ala Arg Pro Gly Ala 4355 4360 4365 Pro Pro Pro Gln Pro Leu Asp Leu Gln His Arg Ala Gln Ala Gly Ala 4370 4375 4380 Asn Thr Arg Pro Cys Pro Ser 4385 4390 <210> SEQ ID NO 90 <211> LENGTH: 198 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 90 Met Asp Ser Leu Leu Met Asn Arg Arg Lys Phe Leu Tyr Gln Phe Lys 1 5 10 15 Asn Val Arg Trp Ala Lys Gly Arg Arg Glu Thr Tyr Leu Cys Tyr Val 20 25 30 Val Lys Arg Arg Asp Ser Ala Thr Ser Phe Ser Leu Asp Phe Gly Tyr 35 40 45 Leu Arg Asn Lys Asn Gly Cys His Val Glu Leu Leu Phe Leu Arg Tyr 50 55 60 Ile Ser Asp Trp Asp Leu Asp Pro Gly Arg Cys Tyr Arg Val Thr Trp 65 70 75 80 Phe Thr Ser Trp Ser Pro Cys Tyr Asp Cys Ala Arg His Val Ala Asp 85 90 95 Phe Leu Arg Gly Asn Pro Asn Leu Ser Leu Arg Ile Phe Thr Ala Arg 100 105 110 Leu Tyr Phe Cys Glu Asp Arg Lys Ala Glu Pro Glu Gly Leu Arg Arg 115 120 125 Leu His Arg Ala Gly Val Gln Ile Ala Ile Met Thr Phe Lys Asp Tyr 130 135 140 Phe Tyr Cys Trp Asn Thr Phe Val Glu Asn His Glu Arg Thr Phe Lys 145 150 155 160 Ala Trp Glu Gly Leu His Glu Asn Ser Val Arg Leu Ser Arg Gln Leu 165 170 175 Arg Arg Ile Leu Leu Pro Leu Tyr Glu Val Asp Asp Leu Arg Asp Ala 180 185 190 Phe Arg Thr Leu Gly Leu 195 <210> SEQ ID NO 91 <211> LENGTH: 491 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 91 Met Glu Leu Ser Val Leu Leu Phe Leu Ala Leu Leu Thr Gly Leu Leu 1 5 10 15 Leu Leu Leu Val Gln Arg His Pro Asn Thr His Asp Arg Leu Pro Pro 20 25 30 Gly Pro Arg Pro Leu Pro Leu Leu Gly Asn Leu Leu Gln Met Asp Arg 35 40 45 Arg Gly Leu Leu Lys Ser Phe Leu Arg Phe Arg Glu Lys Tyr Gly Asp 50 55 60 Val Phe Thr Val His Leu Gly Pro Arg Pro Val Val Met Leu Cys Gly 65 70 75 80 Val Glu Ala Ile Arg Glu Ala Leu Val Asp Lys Ala Glu Ala Phe Ser 85 90 95 Gly Arg Gly Lys Ile Ala Met Val Asp Pro Phe Phe Arg Gly Tyr Gly 100 105 110 Val Ile Phe Ala Asn Gly Asn Arg Trp Lys Val Leu Arg Arg Phe Ser 115 120 125 Val Thr Thr Met Arg Asp Phe Gly Met Gly Lys Arg Ser Val Glu Glu 130 135 140 Arg Ile Gln Glu Glu Ala Gln Cys Leu Ile Glu Glu Leu Arg Lys Ser 145 150 155 160 Lys Gly Ala Leu Met Asp Pro Thr Phe Leu Phe Gln Ser Ile Thr Ala 165 170 175 Asn Ile Ile Cys Ser Ile Val Phe Gly Lys Arg Phe His Tyr Gln Asp 180 185 190 Gln Glu Phe Leu Lys Met Leu Asn Leu Phe Tyr Gln Thr Phe Ser Leu

195 200 205 Ile Ser Ser Val Phe Gly Gln Leu Phe Glu Leu Phe Ser Gly Phe Leu 210 215 220 Lys Tyr Phe Pro Gly Ala His Arg Gln Val Tyr Lys Asn Leu Gln Glu 225 230 235 240 Ile Asn Ala Tyr Ile Gly His Ser Val Glu Lys His Arg Glu Thr Leu 245 250 255 Asp Pro Ser Ala Pro Lys Asp Leu Ile Asp Thr Tyr Leu Leu His Met 260 265 270 Glu Lys Glu Lys Ser Asn Ala His Ser Glu Phe Ser His Gln Asn Leu 275 280 285 Asn Leu Asn Thr Leu Ser Leu Phe Phe Ala Gly Thr Glu Thr Thr Ser 290 295 300 Thr Thr Leu Arg Tyr Gly Phe Leu Leu Met Leu Lys Tyr Pro His Val 305 310 315 320 Ala Glu Arg Val Tyr Arg Glu Ile Glu Gln Val Ile Gly Pro His Arg 325 330 335 Pro Pro Glu Leu His Asp Arg Ala Lys Met Pro Tyr Thr Glu Ala Val 340 345 350 Ile Tyr Glu Ile Gln Arg Phe Ser Asp Leu Leu Pro Met Gly Val Pro 355 360 365 His Ile Val Thr Gln His Thr Ser Phe Arg Gly Tyr Ile Ile Pro Lys 370 375 380 Asp Thr Glu Val Phe Leu Ile Leu Ser Thr Ala Leu His Asp Pro His 385 390 395 400 Tyr Phe Glu Lys Pro Asp Ala Phe Asn Pro Asp His Phe Leu Asp Ala 405 410 415 Asn Gly Ala Leu Lys Lys Thr Glu Ala Phe Ile Pro Phe Ser Leu Gly 420 425 430 Lys Arg Ile Cys Leu Gly Glu Gly Ile Ala Arg Ala Glu Leu Phe Leu 435 440 445 Phe Phe Thr Thr Ile Leu Gln Asn Phe Ser Met Ala Ser Pro Val Ala 450 455 460 Pro Glu Asp Ile Asp Leu Thr Pro Gln Glu Cys Gly Val Gly Lys Ile 465 470 475 480 Pro Pro Thr Tyr Gln Ile Arg Phe Leu Pro Arg 485 490 <210> SEQ ID NO 92 <211> LENGTH: 454 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 92 Met Asp Phe Phe Arg Val Val Glu Asn Gln Gln Pro Pro Ala Thr Met 1 5 10 15 Pro Leu Asn Val Ser Phe Thr Asn Arg Asn Tyr Asp Leu Asp Tyr Asp 20 25 30 Ser Val Gln Pro Tyr Phe Tyr Cys Asp Glu Glu Glu Asn Phe Tyr Gln 35 40 45 Gln Gln Gln Gln Ser Glu Leu Gln Pro Pro Ala Pro Ser Glu Asp Ile 50 55 60 Trp Lys Lys Phe Glu Leu Leu Pro Thr Pro Pro Leu Ser Pro Ser Arg 65 70 75 80 Arg Ser Gly Leu Cys Ser Pro Ser Tyr Val Ala Val Thr Pro Phe Ser 85 90 95 Leu Arg Gly Asp Asn Asp Gly Gly Gly Gly Ser Phe Ser Thr Ala Asp 100 105 110 Gln Leu Glu Met Val Thr Glu Leu Leu Gly Gly Asp Met Val Asn Gln 115 120 125 Ser Phe Ile Cys Asp Pro Asp Asp Glu Thr Phe Ile Lys Asn Ile Ile 130 135 140 Ile Gln Asp Cys Met Trp Ser Gly Phe Ser Ala Ala Ala Lys Leu Val 145 150 155 160 Ser Glu Lys Leu Ala Ser Tyr Gln Ala Ala Arg Lys Asp Ser Gly Ser 165 170 175 Pro Asn Pro Ala Arg Gly His Ser Val Cys Ser Thr Ser Ser Leu Tyr 180 185 190 Leu Gln Asp Leu Ser Ala Ala Ala Ser Glu Cys Ile Asp Pro Ser Val 195 200 205 Val Phe Pro Tyr Pro Leu Asn Asp Ser Ser Ser Pro Lys Ser Cys Ala 210 215 220 Ser Gln Asp Ser Ser Ala Phe Ser Pro Ser Ser Asp Ser Leu Leu Ser 225 230 235 240 Ser Thr Glu Ser Ser Pro Gln Gly Ser Pro Glu Pro Leu Val Leu His 245 250 255 Glu Glu Thr Pro Pro Thr Thr Ser Ser Asp Ser Glu Glu Glu Gln Glu 260 265 270 Asp Glu Glu Glu Ile Asp Val Val Ser Val Glu Lys Arg Gln Ala Pro 275 280 285 Gly Lys Arg Ser Glu Ser Gly Ser Pro Ser Ala Gly Gly His Ser Lys 290 295 300 Pro Pro His Ser Pro Leu Val Leu Lys Arg Cys His Val Ser Thr His 305 310 315 320 Gln His Asn Tyr Ala Ala Pro Pro Ser Thr Arg Lys Asp Tyr Pro Ala 325 330 335 Ala Lys Arg Val Lys Leu Asp Ser Val Arg Val Leu Arg Gln Ile Ser 340 345 350 Asn Asn Arg Lys Cys Thr Ser Pro Arg Ser Ser Asp Thr Glu Glu Asn 355 360 365 Val Lys Arg Arg Thr His Asn Val Leu Glu Arg Gln Arg Arg Asn Glu 370 375 380 Leu Lys Arg Ser Phe Phe Ala Leu Arg Asp Gln Ile Pro Glu Leu Glu 385 390 395 400 Asn Asn Glu Lys Ala Pro Lys Val Val Ile Leu Lys Lys Ala Thr Ala 405 410 415 Tyr Ile Leu Ser Val Gln Ala Glu Glu Gln Lys Leu Ile Ser Glu Glu 420 425 430 Asp Leu Leu Arg Lys Arg Arg Glu Gln Leu Lys His Lys Leu Glu Gln 435 440 445 Leu Arg Asn Ser Cys Ala 450 <210> SEQ ID NO 93 <211> LENGTH: 894 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 93 Met Ile Leu Leu Ala Val Leu Phe Leu Cys Phe Ile Ser Ser Tyr Ser 1 5 10 15 Ala Ser Val Lys Gly His Thr Thr Gly Leu Ser Leu Asn Asn Asp Arg 20 25 30 Leu Tyr Lys Leu Thr Tyr Ser Thr Glu Val Leu Leu Asp Arg Gly Lys 35 40 45 Gly Lys Leu Gln Asp Ser Val Gly Tyr Arg Ile Ser Ser Asn Val Asp 50 55 60 Val Ala Leu Leu Trp Arg Asn Pro Asp Gly Asp Asp Asp Gln Leu Ile 65 70 75 80 Gln Ile Thr Met Lys Asp Val Asn Val Glu Asn Val Asn Gln Gln Arg 85 90 95 Gly Glu Lys Ser Ile Phe Lys Gly Lys Ser Pro Ser Lys Ile Met Gly 100 105 110 Lys Glu Asn Leu Glu Ala Leu Gln Arg Pro Thr Leu Leu His Leu Ile 115 120 125 His Gly Lys Val Lys Glu Phe Tyr Ser Tyr Gln Asn Glu Ala Val Ala 130 135 140 Ile Glu Asn Ile Lys Arg Gly Leu Ala Ser Leu Phe Gln Thr Gln Leu 145 150 155 160 Ser Ser Gly Thr Thr Asn Glu Val Asp Ile Ser Gly Asn Cys Lys Val 165 170 175 Thr Tyr Gln Ala His Gln Asp Lys Val Ile Lys Ile Lys Ala Leu Asp 180 185 190 Ser Cys Lys Ile Ala Arg Ser Gly Phe Thr Thr Pro Asn Gln Val Leu 195 200 205 Gly Val Ser Ser Lys Ala Thr Ser Val Thr Thr Tyr Lys Ile Glu Asp 210 215 220 Ser Phe Val Ile Ala Val Leu Ala Glu Glu Thr His Asn Phe Gly Leu 225 230 235 240 Asn Phe Leu Gln Thr Ile Lys Gly Lys Ile Val Ser Lys Gln Lys Leu 245 250 255 Glu Leu Lys Thr Thr Glu Ala Gly Pro Arg Leu Met Ser Gly Lys Gln 260 265 270 Ala Ala Ala Ile Ile Lys Ala Val Asp Ser Lys Tyr Thr Ala Ile Pro 275 280 285 Ile Val Gly Gln Val Phe Gln Ser His Cys Lys Gly Cys Pro Ser Leu 290 295 300 Ser Glu Leu Trp Arg Ser Thr Arg Lys Tyr Leu Gln Pro Asp Asn Leu 305 310 315 320 Ser Lys Ala Glu Ala Val Arg Asn Phe Leu Ala Phe Ile Gln His Leu 325 330 335 Arg Thr Ala Lys Lys Glu Glu Ile Leu Gln Ile Leu Lys Met Glu Asn 340 345 350 Lys Glu Val Leu Pro Gln Leu Val Asp Ala Val Thr Ser Ala Gln Thr 355 360 365 Ser Asp Ser Leu Glu Ala Ile Leu Asp Phe Leu Asp Phe Lys Ser Asp 370 375 380 Ser Ser Ile Ile Leu Gln Glu Arg Phe Leu Tyr Ala Cys Gly Phe Ala 385 390 395 400 Ser His Pro Asn Glu Glu Leu Leu Arg Ala Leu Ile Ser Lys Phe Lys 405 410 415 Gly Ser Ile Gly Ser Ser Asp Ile Arg Glu Thr Val Met Ile Ile Thr 420 425 430 Gly Thr Leu Val Arg Lys Leu Cys Gln Asn Glu Gly Cys Lys Leu Lys 435 440 445 Ala Val Val Glu Ala Lys Lys Leu Ile Leu Gly Gly Leu Glu Lys Ala 450 455 460 Glu Lys Lys Glu Asp Thr Arg Met Tyr Leu Leu Ala Leu Lys Asn Ala 465 470 475 480 Leu Leu Pro Glu Gly Ile Pro Ser Leu Leu Lys Tyr Ala Glu Ala Gly 485 490 495

Glu Gly Pro Ile Ser His Leu Ala Thr Thr Ala Leu Gln Arg Tyr Asp 500 505 510 Leu Pro Phe Ile Thr Asp Glu Val Lys Lys Thr Leu Asn Arg Ile Tyr 515 520 525 His Gln Asn Arg Lys Val His Glu Lys Thr Val Arg Thr Ala Ala Ala 530 535 540 Ala Ile Ile Leu Asn Asn Asn Pro Ser Tyr Met Asp Val Lys Asn Ile 545 550 555 560 Leu Leu Ser Ile Gly Glu Leu Pro Gln Glu Met Asn Lys Tyr Met Leu 565 570 575 Ala Ile Val Gln Asp Ile Leu Arg Phe Glu Met Pro Ala Ser Lys Ile 580 585 590 Val Arg Arg Val Leu Lys Glu Met Val Ala His Asn Tyr Asp Arg Phe 595 600 605 Ser Arg Ser Gly Ser Ser Ser Ala Tyr Thr Gly Tyr Ile Glu Arg Ser 610 615 620 Pro Arg Ser Ala Ser Thr Tyr Ser Leu Asp Ile Leu Tyr Ser Gly Ser 625 630 635 640 Gly Ile Leu Arg Arg Ser Asn Leu Asn Ile Phe Gln Tyr Ile Gly Lys 645 650 655 Ala Gly Leu His Gly Ser Gln Val Val Ile Glu Ala Gln Gly Leu Glu 660 665 670 Ala Leu Ile Ala Ala Thr Pro Asp Glu Gly Glu Glu Asn Leu Asp Ser 675 680 685 Tyr Ala Gly Met Ser Ala Ile Leu Phe Asp Val Gln Leu Arg Pro Val 690 695 700 Thr Phe Phe Asn Gly Tyr Ser Asp Leu Met Ser Lys Met Leu Ser Ala 705 710 715 720 Ser Gly Asp Pro Ile Ser Val Val Lys Gly Leu Ile Leu Leu Ile Asp 725 730 735 His Ser Gln Glu Leu Gln Leu Gln Ser Gly Leu Lys Ala Asn Ile Glu 740 745 750 Val Gln Gly Gly Leu Ala Ile Asp Ile Ser Gly Ala Met Glu Phe Ser 755 760 765 Leu Trp Tyr Arg Glu Ser Lys Thr Arg Val Lys Asn Arg Val Thr Val 770 775 780 Val Ile Thr Thr Asp Ile Thr Val Asp Ser Ser Phe Val Lys Ala Gly 785 790 795 800 Leu Glu Thr Ser Thr Glu Thr Glu Ala Gly Leu Glu Phe Ile Ser Thr 805 810 815 Val Gln Phe Ser Gln Tyr Pro Phe Leu Val Cys Met Gln Met Asp Lys 820 825 830 Asp Glu Ala Pro Phe Arg Gln Phe Glu Lys Lys Tyr Glu Arg Leu Ser 835 840 845 Thr Gly Arg Gly Tyr Val Ser Gln Lys Arg Lys Glu Ser Val Leu Ala 850 855 860 Gly Cys Glu Phe Pro Leu His Gln Glu Asn Ser Glu Met Cys Lys Val 865 870 875 880 Val Phe Ala Pro Gln Pro Asp Ser Thr Ser Ser Gly Trp Phe 885 890 <210> SEQ ID NO 94 <211> LENGTH: 1210 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 94 Met Arg Pro Ser Gly Thr Ala Gly Ala Ala Leu Leu Ala Leu Leu Ala 1 5 10 15 Ala Leu Cys Pro Ala Ser Arg Ala Leu Glu Glu Lys Lys Val Cys Gln 20 25 30 Gly Thr Ser Asn Lys Leu Thr Gln Leu Gly Thr Phe Glu Asp His Phe 35 40 45 Leu Ser Leu Gln Arg Met Phe Asn Asn Cys Glu Val Val Leu Gly Asn 50 55 60 Leu Glu Ile Thr Tyr Val Gln Arg Asn Tyr Asp Leu Ser Phe Leu Lys 65 70 75 80 Thr Ile Gln Glu Val Ala Gly Tyr Val Leu Ile Ala Leu Asn Thr Val 85 90 95 Glu Arg Ile Pro Leu Glu Asn Leu Gln Ile Ile Arg Gly Asn Met Tyr 100 105 110 Tyr Glu Asn Ser Tyr Ala Leu Ala Val Leu Ser Asn Tyr Asp Ala Asn 115 120 125 Lys Thr Gly Leu Lys Glu Leu Pro Met Arg Asn Leu Gln Glu Ile Leu 130 135 140 His Gly Ala Val Arg Phe Ser Asn Asn Pro Ala Leu Cys Asn Val Glu 145 150 155 160 Ser Ile Gln Trp Arg Asp Ile Val Ser Ser Asp Phe Leu Ser Asn Met 165 170 175 Ser Met Asp Phe Gln Asn His Leu Gly Ser Cys Gln Lys Cys Asp Pro 180 185 190 Ser Cys Pro Asn Gly Ser Cys Trp Gly Ala Gly Glu Glu Asn Cys Gln 195 200 205 Lys Leu Thr Lys Ile Ile Cys Ala Gln Gln Cys Ser Gly Arg Cys Arg 210 215 220 Gly Lys Ser Pro Ser Asp Cys Cys His Asn Gln Cys Ala Ala Gly Cys 225 230 235 240 Thr Gly Pro Arg Glu Ser Asp Cys Leu Val Cys Arg Lys Phe Arg Asp 245 250 255 Glu Ala Thr Cys Lys Asp Thr Cys Pro Pro Leu Met Leu Tyr Asn Pro 260 265 270 Thr Thr Tyr Gln Met Asp Val Asn Pro Glu Gly Lys Tyr Ser Phe Gly 275 280 285 Ala Thr Cys Val Lys Lys Cys Pro Arg Asn Tyr Val Val Thr Asp His 290 295 300 Gly Ser Cys Val Arg Ala Cys Gly Ala Asp Ser Tyr Glu Met Glu Glu 305 310 315 320 Asp Gly Val Arg Lys Cys Lys Lys Cys Glu Gly Pro Cys Arg Lys Val 325 330 335 Cys Asn Gly Ile Gly Ile Gly Glu Phe Lys Asp Ser Leu Ser Ile Asn 340 345 350 Ala Thr Asn Ile Lys His Phe Lys Asn Cys Thr Ser Ile Ser Gly Asp 355 360 365 Leu His Ile Leu Pro Val Ala Phe Arg Gly Asp Ser Phe Thr His Thr 370 375 380 Pro Pro Leu Asp Pro Gln Glu Leu Asp Ile Leu Lys Thr Val Lys Glu 385 390 395 400 Ile Thr Gly Phe Leu Leu Ile Gln Ala Trp Pro Glu Asn Arg Thr Asp 405 410 415 Leu His Ala Phe Glu Asn Leu Glu Ile Ile Arg Gly Arg Thr Lys Gln 420 425 430 His Gly Gln Phe Ser Leu Ala Val Val Ser Leu Asn Ile Thr Ser Leu 435 440 445 Gly Leu Arg Ser Leu Lys Glu Ile Ser Asp Gly Asp Val Ile Ile Ser 450 455 460 Gly Asn Lys Asn Leu Cys Tyr Ala Asn Thr Ile Asn Trp Lys Lys Leu 465 470 475 480 Phe Gly Thr Ser Gly Gln Lys Thr Lys Ile Ile Ser Asn Arg Gly Glu 485 490 495 Asn Ser Cys Lys Ala Thr Gly Gln Val Cys His Ala Leu Cys Ser Pro 500 505 510 Glu Gly Cys Trp Gly Pro Glu Pro Arg Asp Cys Val Ser Cys Arg Asn 515 520 525 Val Ser Arg Gly Arg Glu Cys Val Asp Lys Cys Asn Leu Leu Glu Gly 530 535 540 Glu Pro Arg Glu Phe Val Glu Asn Ser Glu Cys Ile Gln Cys His Pro 545 550 555 560 Glu Cys Leu Pro Gln Ala Met Asn Ile Thr Cys Thr Gly Arg Gly Pro 565 570 575 Asp Asn Cys Ile Gln Cys Ala His Tyr Ile Asp Gly Pro His Cys Val 580 585 590 Lys Thr Cys Pro Ala Gly Val Met Gly Glu Asn Asn Thr Leu Val Trp 595 600 605 Lys Tyr Ala Asp Ala Gly His Val Cys His Leu Cys His Pro Asn Cys 610 615 620 Thr Tyr Gly Cys Thr Gly Pro Gly Leu Glu Gly Cys Pro Thr Asn Gly 625 630 635 640 Pro Lys Ile Pro Ser Ile Ala Thr Gly Met Val Gly Ala Leu Leu Leu 645 650 655 Leu Leu Val Val Ala Leu Gly Ile Gly Leu Phe Met Arg Arg Arg His 660 665 670 Ile Val Arg Lys Arg Thr Leu Arg Arg Leu Leu Gln Glu Arg Glu Leu 675 680 685 Val Glu Pro Leu Thr Pro Ser Gly Glu Ala Pro Asn Gln Ala Leu Leu 690 695 700 Arg Ile Leu Lys Glu Thr Glu Phe Lys Lys Ile Lys Val Leu Gly Ser 705 710 715 720 Gly Ala Phe Gly Thr Val Tyr Lys Gly Leu Trp Ile Pro Glu Gly Glu 725 730 735 Lys Val Lys Ile Pro Val Ala Ile Lys Glu Leu Arg Glu Ala Thr Ser 740 745 750 Pro Lys Ala Asn Lys Glu Ile Leu Asp Glu Ala Tyr Val Met Ala Ser 755 760 765 Val Asp Asn Pro His Val Cys Arg Leu Leu Gly Ile Cys Leu Thr Ser 770 775 780 Thr Val Gln Leu Ile Thr Gln Leu Met Pro Phe Gly Cys Leu Leu Asp 785 790 795 800 Tyr Val Arg Glu His Lys Asp Asn Ile Gly Ser Gln Tyr Leu Leu Asn 805 810 815 Trp Cys Val Gln Ile Ala Lys Gly Met Asn Tyr Leu Glu Asp Arg Arg 820 825 830 Leu Val His Arg Asp Leu Ala Ala Arg Asn Val Leu Val Lys Thr Pro 835 840 845 Gln His Val Lys Ile Thr Asp Phe Gly Leu Ala Lys Leu Leu Gly Ala 850 855 860 Glu Glu Lys Glu Tyr His Ala Glu Gly Gly Lys Val Pro Ile Lys Trp 865 870 875 880 Met Ala Leu Glu Ser Ile Leu His Arg Ile Tyr Thr His Gln Ser Asp 885 890 895

Val Trp Ser Tyr Gly Val Thr Val Trp Glu Leu Met Thr Phe Gly Ser 900 905 910 Lys Pro Tyr Asp Gly Ile Pro Ala Ser Glu Ile Ser Ser Ile Leu Glu 915 920 925 Lys Gly Glu Arg Leu Pro Gln Pro Pro Ile Cys Thr Ile Asp Val Tyr 930 935 940 Met Ile Met Val Lys Cys Trp Met Ile Asp Ala Asp Ser Arg Pro Lys 945 950 955 960 Phe Arg Glu Leu Ile Ile Glu Phe Ser Lys Met Ala Arg Asp Pro Gln 965 970 975 Arg Tyr Leu Val Ile Gln Gly Asp Glu Arg Met His Leu Pro Ser Pro 980 985 990 Thr Asp Ser Asn Phe Tyr Arg Ala Leu Met Asp Glu Glu Asp Met Asp 995 1000 1005 Asp Val Val Asp Ala Asp Glu Tyr Leu Ile Pro Gln Gln Gly Phe Phe 1010 1015 1020 Ser Ser Pro Ser Thr Ser Arg Thr Pro Leu Leu Ser Ser Leu Ser Ala 1025 1030 1035 1040 Thr Ser Asn Asn Ser Thr Val Ala Cys Ile Asp Arg Asn Gly Leu Gln 1045 1050 1055 Ser Cys Pro Ile Lys Glu Asp Ser Phe Leu Gln Arg Tyr Ser Ser Asp 1060 1065 1070 Pro Thr Gly Ala Leu Thr Glu Asp Ser Ile Asp Asp Thr Phe Leu Pro 1075 1080 1085 Val Pro Glu Tyr Ile Asn Gln Ser Val Pro Lys Arg Pro Ala Gly Ser 1090 1095 1100 Val Gln Asn Pro Val Tyr His Asn Gln Pro Leu Asn Pro Ala Pro Ser 1105 1110 1115 1120 Arg Asp Pro His Tyr Gln Asp Pro His Ser Thr Ala Val Gly Asn Pro 1125 1130 1135 Glu Tyr Leu Asn Thr Val Gln Pro Thr Cys Val Asn Ser Thr Phe Asp 1140 1145 1150 Ser Pro Ala His Trp Ala Gln Lys Gly Ser His Gln Ile Ser Leu Asp 1155 1160 1165 Asn Pro Asp Tyr Gln Gln Asp Phe Phe Pro Lys Glu Ala Lys Pro Asn 1170 1175 1180 Gly Ile Phe Lys Gly Ser Thr Ala Glu Asn Ala Glu Tyr Leu Arg Val 1185 1190 1195 1200 Ala Pro Gln Ser Ser Glu Phe Ile Gly Ala 1205 1210 <210> SEQ ID NO 95 <211> LENGTH: 705 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 95 Met Arg Pro Ser Gly Thr Ala Gly Ala Ala Leu Leu Ala Leu Leu Ala 1 5 10 15 Ala Leu Cys Pro Ala Ser Arg Ala Leu Glu Glu Lys Lys Val Cys Gln 20 25 30 Gly Thr Ser Asn Lys Leu Thr Gln Leu Gly Thr Phe Glu Asp His Phe 35 40 45 Leu Ser Leu Gln Arg Met Phe Asn Asn Cys Glu Val Val Leu Gly Asn 50 55 60 Leu Glu Ile Thr Tyr Val Gln Arg Asn Tyr Asp Leu Ser Phe Leu Lys 65 70 75 80 Thr Ile Gln Glu Val Ala Gly Tyr Val Leu Ile Ala Leu Asn Thr Val 85 90 95 Glu Arg Ile Pro Leu Glu Asn Leu Gln Ile Ile Arg Gly Asn Met Tyr 100 105 110 Tyr Glu Asn Ser Tyr Ala Leu Ala Val Leu Ser Asn Tyr Asp Ala Asn 115 120 125 Lys Thr Gly Leu Lys Glu Leu Pro Met Arg Asn Leu Gln Glu Ile Leu 130 135 140 His Gly Ala Val Arg Phe Ser Asn Asn Pro Ala Leu Cys Asn Val Glu 145 150 155 160 Ser Ile Gln Trp Arg Asp Ile Val Ser Ser Asp Phe Leu Ser Asn Met 165 170 175 Ser Met Asp Phe Gln Asn His Leu Gly Ser Cys Gln Lys Cys Asp Pro 180 185 190 Ser Cys Pro Asn Gly Ser Cys Trp Gly Ala Gly Glu Glu Asn Cys Gln 195 200 205 Lys Leu Thr Lys Ile Ile Cys Ala Gln Gln Cys Ser Gly Arg Cys Arg 210 215 220 Gly Lys Ser Pro Ser Asp Cys Cys His Asn Gln Cys Ala Ala Gly Cys 225 230 235 240 Thr Gly Pro Arg Glu Ser Asp Cys Leu Val Cys Arg Lys Phe Arg Asp 245 250 255 Glu Ala Thr Cys Lys Asp Thr Cys Pro Pro Leu Met Leu Tyr Asn Pro 260 265 270 Thr Thr Tyr Gln Met Asp Val Asn Pro Glu Gly Lys Tyr Ser Phe Gly 275 280 285 Ala Thr Cys Val Lys Lys Cys Pro Arg Asn Tyr Val Val Thr Asp His 290 295 300 Gly Ser Cys Val Arg Ala Cys Gly Ala Asp Ser Tyr Glu Met Glu Glu 305 310 315 320 Asp Gly Val Arg Lys Cys Lys Lys Cys Glu Gly Pro Cys Arg Lys Val 325 330 335 Cys Asn Gly Ile Gly Ile Gly Glu Phe Lys Asp Ser Leu Ser Ile Asn 340 345 350 Ala Thr Asn Ile Lys His Phe Lys Asn Cys Thr Ser Ile Ser Gly Asp 355 360 365 Leu His Ile Leu Pro Val Ala Phe Arg Gly Asp Ser Phe Thr His Thr 370 375 380 Pro Pro Leu Asp Pro Gln Glu Leu Asp Ile Leu Lys Thr Val Lys Glu 385 390 395 400 Ile Thr Gly Phe Leu Leu Ile Gln Ala Trp Pro Glu Asn Arg Thr Asp 405 410 415 Leu His Ala Phe Glu Asn Leu Glu Ile Ile Arg Gly Arg Thr Lys Gln 420 425 430 His Gly Gln Phe Ser Leu Ala Val Val Ser Leu Asn Ile Thr Ser Leu 435 440 445 Gly Leu Arg Ser Leu Lys Glu Ile Ser Asp Gly Asp Val Ile Ile Ser 450 455 460 Gly Asn Lys Asn Leu Cys Tyr Ala Asn Thr Ile Asn Trp Lys Lys Leu 465 470 475 480 Phe Gly Thr Ser Gly Gln Lys Thr Lys Ile Ile Ser Asn Arg Gly Glu 485 490 495 Asn Ser Cys Lys Ala Thr Gly Gln Val Cys His Ala Leu Cys Ser Pro 500 505 510 Glu Gly Cys Trp Gly Pro Glu Pro Arg Asp Cys Val Ser Cys Arg Asn 515 520 525 Val Ser Arg Gly Arg Glu Cys Val Asp Lys Cys Asn Leu Leu Glu Gly 530 535 540 Glu Pro Arg Glu Phe Val Glu Asn Ser Glu Cys Ile Gln Cys His Pro 545 550 555 560 Glu Cys Leu Pro Gln Ala Met Asn Ile Thr Cys Thr Gly Arg Gly Pro 565 570 575 Asp Asn Cys Ile Gln Cys Ala His Tyr Ile Asp Gly Pro His Cys Val 580 585 590 Lys Thr Cys Pro Ala Gly Val Met Gly Glu Asn Asn Thr Leu Val Trp 595 600 605 Lys Tyr Ala Asp Ala Gly His Val Cys His Leu Cys His Pro Asn Cys 610 615 620 Thr Tyr Gly Pro Gly Asn Glu Ser Leu Lys Ala Met Leu Phe Cys Leu 625 630 635 640 Phe Lys Leu Ser Ser Cys Asn Gln Ser Asn Asp Gly Ser Val Ser His 645 650 655 Gln Ser Gly Ser Pro Ala Ala Gln Glu Ser Cys Leu Gly Trp Ile Pro 660 665 670 Ser Leu Leu Pro Ser Glu Phe Gln Leu Gly Trp Gly Gly Cys Ser His 675 680 685 Leu His Ala Trp Pro Ser Ala Ser Val Ile Ile Thr Ala Ser Ser Cys 690 695 700 His 705 <210> SEQ ID NO 96 <211> LENGTH: 628 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 96 Met Arg Pro Ser Gly Thr Ala Gly Ala Ala Leu Leu Ala Leu Leu Ala 1 5 10 15 Ala Leu Cys Pro Ala Ser Arg Ala Leu Glu Glu Lys Lys Val Cys Gln 20 25 30 Gly Thr Ser Asn Lys Leu Thr Gln Leu Gly Thr Phe Glu Asp His Phe 35 40 45 Leu Ser Leu Gln Arg Met Phe Asn Asn Cys Glu Val Val Leu Gly Asn 50 55 60 Leu Glu Ile Thr Tyr Val Gln Arg Asn Tyr Asp Leu Ser Phe Leu Lys 65 70 75 80 Thr Ile Gln Glu Val Ala Gly Tyr Val Leu Ile Ala Leu Asn Thr Val 85 90 95 Glu Arg Ile Pro Leu Glu Asn Leu Gln Ile Ile Arg Gly Asn Met Tyr 100 105 110 Tyr Glu Asn Ser Tyr Ala Leu Ala Val Leu Ser Asn Tyr Asp Ala Asn 115 120 125 Lys Thr Gly Leu Lys Glu Leu Pro Met Arg Asn Leu Gln Glu Ile Leu 130 135 140 His Gly Ala Val Arg Phe Ser Asn Asn Pro Ala Leu Cys Asn Val Glu 145 150 155 160 Ser Ile Gln Trp Arg Asp Ile Val Ser Ser Asp Phe Leu Ser Asn Met 165 170 175 Ser Met Asp Phe Gln Asn His Leu Gly Ser Cys Gln Lys Cys Asp Pro 180 185 190 Ser Cys Pro Asn Gly Ser Cys Trp Gly Ala Gly Glu Glu Asn Cys Gln 195 200 205

Lys Leu Thr Lys Ile Ile Cys Ala Gln Gln Cys Ser Gly Arg Cys Arg 210 215 220 Gly Lys Ser Pro Ser Asp Cys Cys His Asn Gln Cys Ala Ala Gly Cys 225 230 235 240 Thr Gly Pro Arg Glu Ser Asp Cys Leu Val Cys Arg Lys Phe Arg Asp 245 250 255 Glu Ala Thr Cys Lys Asp Thr Cys Pro Pro Leu Met Leu Tyr Asn Pro 260 265 270 Thr Thr Tyr Gln Met Asp Val Asn Pro Glu Gly Lys Tyr Ser Phe Gly 275 280 285 Ala Thr Cys Val Lys Lys Cys Pro Arg Asn Tyr Val Val Thr Asp His 290 295 300 Gly Ser Cys Val Arg Ala Cys Gly Ala Asp Ser Tyr Glu Met Glu Glu 305 310 315 320 Asp Gly Val Arg Lys Cys Lys Lys Cys Glu Gly Pro Cys Arg Lys Val 325 330 335 Cys Asn Gly Ile Gly Ile Gly Glu Phe Lys Asp Ser Leu Ser Ile Asn 340 345 350 Ala Thr Asn Ile Lys His Phe Lys Asn Cys Thr Ser Ile Ser Gly Asp 355 360 365 Leu His Ile Leu Pro Val Ala Phe Arg Gly Asp Ser Phe Thr His Thr 370 375 380 Pro Pro Leu Asp Pro Gln Glu Leu Asp Ile Leu Lys Thr Val Lys Glu 385 390 395 400 Ile Thr Gly Phe Leu Leu Ile Gln Ala Trp Pro Glu Asn Arg Thr Asp 405 410 415 Leu His Ala Phe Glu Asn Leu Glu Ile Ile Arg Gly Arg Thr Lys Gln 420 425 430 His Gly Gln Phe Ser Leu Ala Val Val Ser Leu Asn Ile Thr Ser Leu 435 440 445 Gly Leu Arg Ser Leu Lys Glu Ile Ser Asp Gly Asp Val Ile Ile Ser 450 455 460 Gly Asn Lys Asn Leu Cys Tyr Ala Asn Thr Ile Asn Trp Lys Lys Leu 465 470 475 480 Phe Gly Thr Ser Gly Gln Lys Thr Lys Ile Ile Ser Asn Arg Gly Glu 485 490 495 Asn Ser Cys Lys Ala Thr Gly Gln Val Cys His Ala Leu Cys Ser Pro 500 505 510 Glu Gly Cys Trp Gly Pro Glu Pro Arg Asp Cys Val Ser Cys Arg Asn 515 520 525 Val Ser Arg Gly Arg Glu Cys Val Asp Lys Cys Asn Leu Leu Glu Gly 530 535 540 Glu Pro Arg Glu Phe Val Glu Asn Ser Glu Cys Ile Gln Cys His Pro 545 550 555 560 Glu Cys Leu Pro Gln Ala Met Asn Ile Thr Cys Thr Gly Arg Gly Pro 565 570 575 Asp Asn Cys Ile Gln Cys Ala His Tyr Ile Asp Gly Pro His Cys Val 580 585 590 Lys Thr Cys Pro Ala Gly Val Met Gly Glu Asn Asn Thr Leu Val Trp 595 600 605 Lys Tyr Ala Asp Ala Gly His Val Cys His Leu Cys His Pro Asn Cys 610 615 620 Thr Tyr Gly Ser 625 <210> SEQ ID NO 97 <211> LENGTH: 242 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 97 Met Ser Gly Cys Asp Ala Arg Glu Gly Asp Cys Cys Ser Arg Arg Cys 1 5 10 15 Gly Ala Gln Asp Lys Glu His Pro Arg Tyr Leu Ile Pro Glu Leu Cys 20 25 30 Lys Gln Phe Tyr His Leu Gly Trp Val Thr Gly Thr Gly Gly Gly Ile 35 40 45 Ser Leu Lys His Gly Asp Glu Ile Tyr Ile Ala Pro Ser Gly Val Gln 50 55 60 Lys Glu Arg Ile Gln Pro Glu Asp Met Phe Val Cys Asp Ile Asn Glu 65 70 75 80 Lys Asp Ile Ser Gly Pro Ser Pro Ser Lys Lys Leu Lys Lys Ser Gln 85 90 95 Cys Thr Pro Leu Phe Met Asn Ala Tyr Thr Met Arg Gly Ala Gly Ala 100 105 110 Val Ile His Thr His Ser Lys Ala Ala Val Met Ala Thr Leu Leu Phe 115 120 125 Pro Gly Arg Glu Phe Lys Ile Thr His Gln Glu Met Ile Lys Gly Ile 130 135 140 Lys Lys Cys Thr Ser Gly Gly Tyr Tyr Arg Tyr Asp Asp Met Leu Val 145 150 155 160 Val Pro Ile Ile Glu Asn Thr Pro Glu Glu Lys Asp Leu Lys Asp Arg 165 170 175 Met Ala His Ala Met Asn Glu Tyr Pro Asp Ser Cys Ala Val Leu Val 180 185 190 Arg Arg His Gly Val Tyr Val Trp Gly Glu Thr Trp Glu Lys Ala Lys 195 200 205 Thr Met Cys Glu Cys Tyr Asp Tyr Leu Phe Asp Ile Ala Val Ser Met 210 215 220 Lys Lys Val Gly Leu Asp Pro Ser Gln Leu Pro Val Gly Glu Asn Gly 225 230 235 240 Ile Val <210> SEQ ID NO 98 <211> LENGTH: 367 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 98 Met Arg Trp Phe Leu Pro Trp Thr Leu Ala Ala Val Thr Ala Ala Ala 1 5 10 15 Ala Ser Thr Val Leu Ala Thr Ala Leu Ser Pro Ala Pro Thr Thr Met 20 25 30 Asp Phe Thr Pro Ala Pro Leu Glu Asp Thr Ser Ser Arg Pro Gln Phe 35 40 45 Cys Lys Trp Pro Cys Glu Cys Pro Pro Ser Pro Pro Arg Cys Pro Leu 50 55 60 Gly Val Ser Leu Ile Thr Asp Gly Cys Glu Cys Cys Lys Met Cys Ala 65 70 75 80 Gln Gln Leu Gly Asp Asn Cys Thr Glu Ala Ala Ile Cys Asp Pro His 85 90 95 Arg Gly Leu Tyr Cys Asp Tyr Ser Gly Asp Arg Pro Arg Tyr Ala Ile 100 105 110 Gly Val Cys Ala Gln Val Val Gly Val Gly Cys Val Leu Asp Gly Val 115 120 125 Arg Tyr Asn Asn Gly Gln Ser Phe Gln Pro Asn Cys Lys Tyr Asn Cys 130 135 140 Thr Cys Ile Asp Gly Ala Val Gly Cys Thr Pro Leu Cys Leu Arg Val 145 150 155 160 Arg Pro Pro Arg Leu Trp Cys Pro His Pro Arg Arg Val Ser Ile Pro 165 170 175 Gly His Cys Cys Glu Gln Trp Val Cys Glu Asp Asp Ala Lys Arg Pro 180 185 190 Arg Lys Thr Ala Pro Arg Asp Thr Gly Ala Phe Asp Ala Val Gly Glu 195 200 205 Val Glu Ala Trp His Arg Asn Cys Ile Ala Tyr Thr Ser Pro Trp Ser 210 215 220 Pro Cys Ser Thr Ser Cys Gly Leu Gly Val Ser Thr Arg Ile Ser Asn 225 230 235 240 Val Asn Ala Gln Cys Trp Pro Glu Gln Glu Ser Arg Leu Cys Asn Leu 245 250 255 Arg Pro Cys Asp Val Asp Ile His Thr Leu Ile Lys Ala Gly Lys Lys 260 265 270 Cys Leu Ala Val Tyr Gln Pro Glu Ala Ser Met Asn Phe Thr Leu Ala 275 280 285 Gly Cys Ile Ser Thr Arg Ser Tyr Gln Pro Lys Tyr Cys Gly Val Cys 290 295 300 Met Asp Asn Arg Cys Cys Ile Pro Tyr Lys Ser Lys Thr Ile Asp Val 305 310 315 320 Ser Phe Gln Cys Pro Asp Gly Leu Gly Phe Ser Arg Gln Val Leu Trp 325 330 335 Ile Asn Ala Cys Phe Cys Asn Leu Ser Cys Arg Asn Pro Asn Asp Ile 340 345 350 Phe Ala Asp Leu Glu Ser Tyr Pro Asp Phe Ser Glu Ile Ala Asn 355 360 365 <210> SEQ ID NO 99 <211> LENGTH: 280 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 99 Met Arg Trp Phe Leu Pro Trp Thr Leu Ala Ala Val Thr Ala Ala Ala 1 5 10 15 Ala Ser Thr Val Leu Ala Thr Ala Leu Ser Pro Ala Pro Thr Thr Met 20 25 30 Asp Phe Thr Pro Ala Pro Leu Glu Asp Thr Ser Ser Arg Pro Gln Phe 35 40 45 Cys Lys Trp Pro Cys Glu Cys Pro Pro Ser Pro Pro Arg Cys Pro Leu 50 55 60 Gly Val Ser Leu Ile Thr Asp Gly Cys Glu Cys Cys Lys Met Cys Ala 65 70 75 80 Gln Gln Leu Gly Asp Asn Cys Thr Glu Ala Ala Ile Cys Asp Pro His 85 90 95 Arg Gly Leu Tyr Cys Asp Tyr Ser Gly Asp Arg Pro Arg Tyr Ala Ile 100 105 110 Gly Val Cys Ala His Ala Val Gly Glu Val Glu Ala Trp His Arg Asn 115 120 125 Cys Ile Ala Tyr Thr Ser Pro Trp Ser Pro Cys Ser Thr Ser Cys Gly 130 135 140 Leu Gly Val Ser Thr Arg Ile Ser Asn Val Asn Ala Gln Cys Trp Pro 145 150 155 160

Glu Gln Glu Ser Arg Leu Cys Asn Leu Arg Pro Cys Asp Val Asp Ile 165 170 175 His Thr Leu Ile Lys Ala Gly Lys Lys Cys Leu Ala Val Tyr Gln Pro 180 185 190 Glu Ala Ser Met Asn Phe Thr Leu Ala Gly Cys Ile Ser Thr Arg Ser 195 200 205 Tyr Gln Pro Lys Tyr Cys Gly Val Cys Met Asp Asn Arg Cys Cys Ile 210 215 220 Pro Tyr Lys Ser Lys Thr Ile Asp Val Ser Phe Gln Cys Pro Asp Gly 225 230 235 240 Leu Gly Phe Ser Arg Gln Val Leu Trp Ile Asn Ala Cys Phe Cys Asn 245 250 255 Leu Ser Cys Arg Asn Pro Asn Asp Ile Phe Ala Asp Leu Glu Ser Tyr 260 265 270 Pro Asp Phe Ser Glu Ile Ala Asn 275 280 <210> SEQ ID NO 100 <211> LENGTH: 370 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 100 Met Gly Leu Trp Ala Leu Leu Pro Gly Trp Val Ser Ala Thr Leu Leu 1 5 10 15 Leu Ala Leu Ala Ala Leu Pro Ala Ala Leu Ala Ala Asn Ser Ser Gly 20 25 30 Arg Trp Trp Gly Ile Val Asn Val Ala Ser Ser Thr Asn Leu Leu Thr 35 40 45 Asp Ser Lys Ser Leu Gln Leu Val Leu Glu Pro Ser Leu Gln Leu Leu 50 55 60 Ser Arg Lys Gln Arg Arg Leu Ile Arg Gln Asn Pro Gly Ile Leu His 65 70 75 80 Ser Val Ser Gly Gly Leu Gln Ser Ala Val Arg Glu Cys Lys Trp Gln 85 90 95 Phe Arg Asn Arg Arg Trp Asn Cys Pro Thr Ala Pro Gly Pro His Leu 100 105 110 Phe Gly Lys Ile Val Asn Arg Gly Cys Arg Glu Thr Ala Phe Ile Phe 115 120 125 Ala Ile Thr Ser Ala Gly Val Thr His Ser Val Ala Arg Ser Cys Ser 130 135 140 Glu Gly Ser Ile Glu Ser Cys Thr Cys Asp Tyr Arg Arg Arg Gly Pro 145 150 155 160 Gly Gly Pro Asp Trp His Trp Gly Gly Cys Ser Asp Asn Ile Asp Phe 165 170 175 Gly Arg Leu Phe Gly Arg Glu Phe Val Asp Ser Gly Glu Lys Gly Arg 180 185 190 Asp Leu Arg Phe Leu Met Asn Leu His Asn Asn Glu Ala Gly Arg Thr 195 200 205 Thr Val Phe Ser Glu Met Arg Gln Glu Cys Lys Cys His Gly Met Ser 210 215 220 Gly Ser Cys Thr Val Arg Thr Cys Trp Met Arg Leu Pro Thr Leu Arg 225 230 235 240 Ala Val Gly Asp Val Leu Arg Asp Arg Phe Asp Gly Ala Ser Arg Val 245 250 255 Leu Tyr Gly Asn Arg Gly Ser Asn Arg Ala Ser Arg Ala Glu Leu Leu 260 265 270 Arg Leu Glu Pro Glu Asp Pro Ala His Lys Pro Pro Ser Pro His Asp 275 280 285 Leu Val Tyr Phe Glu Lys Ser Pro Asn Phe Cys Thr Tyr Ser Gly Arg 290 295 300 Leu Gly Thr Ala Gly Thr Ala Gly Arg Ala Cys Asn Ser Ser Ser Pro 305 310 315 320 Ala Leu Asp Gly Cys Glu Leu Leu Cys Cys Gly Arg Gly His Arg Thr 325 330 335 Arg Thr Gln Arg Val Thr Glu Arg Cys Asn Cys Thr Phe His Trp Cys 340 345 350 Cys His Val Ser Cys Arg Asn Cys Thr His Thr Arg Val Leu His Glu 355 360 365 Cys Leu 370 <210> SEQ ID NO 101 <211> LENGTH: 648 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 101 Met Glu His Ile Gln Gly Ala Trp Lys Thr Ile Ser Asn Gly Phe Gly 1 5 10 15 Phe Lys Asp Ala Val Phe Asp Gly Ser Ser Cys Ile Ser Pro Thr Ile 20 25 30 Val Gln Gln Phe Gly Tyr Gln Arg Arg Ala Ser Asp Asp Gly Lys Leu 35 40 45 Thr Asp Pro Ser Lys Thr Ser Asn Thr Ile Arg Val Phe Leu Pro Asn 50 55 60 Lys Gln Arg Thr Val Val Asn Val Arg Asn Gly Met Ser Leu His Asp 65 70 75 80 Cys Leu Met Lys Ala Leu Lys Val Arg Gly Leu Gln Pro Glu Cys Cys 85 90 95 Ala Val Phe Arg Leu Leu His Glu His Lys Gly Lys Lys Ala Arg Leu 100 105 110 Asp Trp Asn Thr Asp Ala Ala Ser Leu Ile Gly Glu Glu Leu Gln Val 115 120 125 Asp Phe Leu Asp His Val Pro Leu Thr Thr His Asn Phe Ala Arg Lys 130 135 140 Thr Phe Leu Lys Leu Ala Phe Cys Asp Ile Cys Gln Lys Phe Leu Leu 145 150 155 160 Asn Gly Phe Arg Cys Gln Thr Cys Gly Tyr Lys Phe His Glu His Cys 165 170 175 Ser Thr Lys Val Pro Thr Met Cys Val Asp Trp Ser Asn Ile Arg Gln 180 185 190 Leu Leu Leu Phe Pro Asn Ser Thr Ile Gly Asp Ser Gly Val Pro Ala 195 200 205 Leu Pro Ser Leu Thr Met Arg Arg Met Arg Glu Ser Val Ser Arg Met 210 215 220 Pro Val Ser Ser Gln His Arg Tyr Ser Thr Pro His Ala Phe Thr Phe 225 230 235 240 Asn Thr Ser Ser Pro Ser Ser Glu Gly Ser Leu Ser Gln Arg Gln Arg 245 250 255 Ser Thr Ser Thr Pro Asn Val His Met Val Ser Thr Thr Leu Pro Val 260 265 270 Asp Ser Arg Met Ile Glu Asp Ala Ile Arg Ser His Ser Glu Ser Ala 275 280 285 Ser Pro Ser Ala Leu Ser Ser Ser Pro Asn Asn Leu Ser Pro Thr Gly 290 295 300 Trp Ser Gln Pro Lys Thr Pro Val Pro Ala Gln Arg Glu Arg Ala Pro 305 310 315 320 Val Ser Gly Thr Gln Glu Lys Asn Lys Ile Arg Pro Arg Gly Gln Arg 325 330 335 Asp Ser Ser Tyr Tyr Trp Glu Ile Glu Ala Ser Glu Val Met Leu Ser 340 345 350 Thr Arg Ile Gly Ser Gly Ser Phe Gly Thr Val Tyr Lys Gly Lys Trp 355 360 365 His Gly Asp Val Ala Val Lys Ile Leu Lys Val Val Asp Pro Thr Pro 370 375 380 Glu Gln Phe Gln Ala Phe Arg Asn Glu Val Ala Val Leu Arg Lys Thr 385 390 395 400 Arg His Val Asn Ile Leu Leu Phe Met Gly Tyr Met Thr Lys Asp Asn 405 410 415 Leu Ala Ile Val Thr Gln Trp Cys Glu Gly Ser Ser Leu Tyr Lys His 420 425 430 Leu His Val Gln Glu Thr Lys Phe Gln Met Phe Gln Leu Ile Asp Ile 435 440 445 Ala Arg Gln Thr Ala Gln Gly Met Asp Tyr Leu His Ala Lys Asn Ile 450 455 460 Ile His Arg Asp Met Lys Ser Asn Asn Ile Phe Leu His Glu Gly Leu 465 470 475 480 Thr Val Lys Ile Gly Asp Phe Gly Leu Ala Thr Val Lys Ser Arg Trp 485 490 495 Ser Gly Ser Gln Gln Val Glu Gln Pro Thr Gly Ser Val Leu Trp Met 500 505 510 Ala Pro Glu Val Ile Arg Met Gln Asp Asn Asn Pro Phe Ser Phe Gln 515 520 525 Ser Asp Val Tyr Ser Tyr Gly Ile Val Leu Tyr Glu Leu Met Thr Gly 530 535 540 Glu Leu Pro Tyr Ser His Ile Asn Asn Arg Asp Gln Ile Ile Phe Met 545 550 555 560 Val Gly Arg Gly Tyr Ala Ser Pro Asp Leu Ser Lys Leu Tyr Lys Asn 565 570 575 Cys Pro Lys Ala Met Lys Arg Leu Val Ala Asp Cys Val Lys Lys Val 580 585 590 Lys Glu Glu Arg Pro Leu Phe Pro Gln Ile Leu Ser Ser Ile Glu Leu 595 600 605 Leu Gln His Ser Leu Pro Lys Ile Asn Arg Ser Ala Ser Glu Pro Ser 610 615 620 Leu His Arg Ala Ala His Thr Glu Asp Ile Asn Ala Cys Thr Leu Thr 625 630 635 640 Thr Ser Pro Arg Leu Pro Val Phe 645 <210> SEQ ID NO 102 <211> LENGTH: 536 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 102 Met Gly Ser Asn Lys Ser Lys Pro Lys Asp Ala Ser Gln Arg Arg Arg 1 5 10 15 Ser Leu Glu Pro Ala Glu Asn Val His Gly Ala Gly Gly Gly Ala Phe 20 25 30 Pro Ala Ser Gln Thr Pro Ser Lys Pro Ala Ser Ala Asp Gly His Arg 35 40 45

Gly Pro Ser Ala Ala Phe Ala Pro Ala Ala Ala Glu Pro Lys Leu Phe 50 55 60 Gly Gly Phe Asn Ser Ser Asp Thr Val Thr Ser Pro Gln Arg Ala Gly 65 70 75 80 Pro Leu Ala Gly Gly Val Thr Thr Phe Val Ala Leu Tyr Asp Tyr Glu 85 90 95 Ser Arg Thr Glu Thr Asp Leu Ser Phe Lys Lys Gly Glu Arg Leu Gln 100 105 110 Ile Val Asn Asn Thr Glu Gly Asp Trp Trp Leu Ala His Ser Leu Ser 115 120 125 Thr Gly Gln Thr Gly Tyr Ile Pro Ser Asn Tyr Val Ala Pro Ser Asp 130 135 140 Ser Ile Gln Ala Glu Glu Trp Tyr Phe Gly Lys Ile Thr Arg Arg Glu 145 150 155 160 Ser Glu Arg Leu Leu Leu Asn Ala Glu Asn Pro Arg Gly Thr Phe Leu 165 170 175 Val Arg Glu Ser Glu Thr Thr Lys Gly Ala Tyr Cys Leu Ser Val Ser 180 185 190 Asp Phe Asp Asn Ala Lys Gly Leu Asn Val Lys His Tyr Lys Ile Arg 195 200 205 Lys Leu Asp Ser Gly Gly Phe Tyr Ile Thr Ser Arg Thr Gln Phe Asn 210 215 220 Ser Leu Gln Gln Leu Val Ala Tyr Tyr Ser Lys His Ala Asp Gly Leu 225 230 235 240 Cys His Arg Leu Thr Thr Val Cys Pro Thr Ser Lys Pro Gln Thr Gln 245 250 255 Gly Leu Ala Lys Asp Ala Trp Glu Ile Pro Arg Glu Ser Leu Arg Leu 260 265 270 Glu Val Lys Leu Gly Gln Gly Cys Phe Gly Glu Val Trp Met Gly Thr 275 280 285 Trp Asn Gly Thr Thr Arg Val Ala Ile Lys Thr Leu Lys Pro Gly Thr 290 295 300 Met Ser Pro Glu Ala Phe Leu Gln Glu Ala Gln Val Met Lys Lys Leu 305 310 315 320 Arg His Glu Lys Leu Val Gln Leu Tyr Ala Val Val Ser Glu Glu Pro 325 330 335 Ile Tyr Ile Val Thr Glu Tyr Met Ser Lys Gly Ser Leu Leu Asp Phe 340 345 350 Leu Lys Gly Glu Thr Gly Lys Tyr Leu Arg Leu Pro Gln Leu Val Asp 355 360 365 Met Ala Ala Gln Ile Ala Ser Gly Met Ala Tyr Val Glu Arg Met Asn 370 375 380 Tyr Val His Arg Asp Leu Arg Ala Ala Asn Ile Leu Val Gly Glu Asn 385 390 395 400 Leu Val Cys Lys Val Ala Asp Phe Gly Leu Ala Arg Leu Ile Glu Asp 405 410 415 Asn Glu Tyr Thr Ala Arg Gln Gly Ala Lys Phe Pro Ile Lys Trp Thr 420 425 430 Ala Pro Glu Ala Ala Leu Tyr Gly Arg Phe Thr Ile Lys Ser Asp Val 435 440 445 Trp Ser Phe Gly Ile Leu Leu Thr Glu Leu Thr Thr Lys Gly Arg Val 450 455 460 Pro Tyr Pro Gly Met Val Asn Arg Glu Val Leu Asp Gln Val Glu Arg 465 470 475 480 Gly Tyr Arg Met Pro Cys Pro Pro Glu Cys Pro Glu Ser Leu His Asp 485 490 495 Leu Met Cys Gln Cys Trp Arg Lys Glu Pro Glu Glu Arg Pro Thr Phe 500 505 510 Glu Tyr Leu Gln Ala Phe Leu Glu Asp Tyr Phe Thr Ser Thr Glu Pro 515 520 525 Gln Tyr Gln Pro Gly Glu Asn Leu 530 535 <210> SEQ ID NO 103 <211> LENGTH: 480 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 103 Met Ser Asp Val Ala Ile Val Lys Glu Gly Trp Leu His Lys Arg Gly 1 5 10 15 Glu Tyr Ile Lys Thr Trp Arg Pro Arg Tyr Phe Leu Leu Lys Asn Asp 20 25 30 Gly Thr Phe Ile Gly Tyr Lys Glu Arg Pro Gln Asp Val Asp Gln Arg 35 40 45 Glu Ala Pro Leu Asn Asn Phe Ser Val Ala Gln Cys Gln Leu Met Lys 50 55 60 Thr Glu Arg Pro Arg Pro Asn Thr Phe Ile Ile Arg Cys Leu Gln Trp 65 70 75 80 Thr Thr Val Ile Glu Arg Thr Phe His Val Glu Thr Pro Glu Glu Arg 85 90 95 Glu Glu Trp Thr Thr Ala Ile Gln Thr Val Ala Asp Gly Leu Lys Lys 100 105 110 Gln Glu Glu Glu Glu Met Asp Phe Arg Ser Gly Ser Pro Ser Asp Asn 115 120 125 Ser Gly Ala Glu Glu Met Glu Val Ser Leu Ala Lys Pro Lys His Arg 130 135 140 Val Thr Met Asn Glu Phe Glu Tyr Leu Lys Leu Leu Gly Lys Gly Thr 145 150 155 160 Phe Gly Lys Val Ile Leu Val Lys Glu Lys Ala Thr Gly Arg Tyr Tyr 165 170 175 Ala Met Lys Ile Leu Lys Lys Glu Val Ile Val Ala Lys Asp Glu Val 180 185 190 Ala His Thr Leu Thr Glu Asn Arg Val Leu Gln Asn Ser Arg His Pro 195 200 205 Phe Leu Thr Ala Leu Lys Tyr Ser Phe Gln Thr His Asp Arg Leu Cys 210 215 220 Phe Val Met Glu Tyr Ala Asn Gly Gly Glu Leu Phe Phe His Leu Ser 225 230 235 240 Arg Glu Arg Val Phe Ser Glu Asp Arg Ala Arg Phe Tyr Gly Ala Glu 245 250 255 Ile Val Ser Ala Leu Asp Tyr Leu His Ser Glu Lys Asn Val Val Tyr 260 265 270 Arg Asp Leu Lys Leu Glu Asn Leu Met Leu Asp Lys Asp Gly His Ile 275 280 285 Lys Ile Thr Asp Phe Gly Leu Cys Lys Glu Gly Ile Lys Asp Gly Ala 290 295 300 Thr Met Lys Thr Phe Cys Gly Thr Pro Glu Tyr Leu Ala Pro Glu Val 305 310 315 320 Leu Glu Asp Asn Asp Tyr Gly Arg Ala Val Asp Trp Trp Gly Leu Gly 325 330 335 Val Val Met Tyr Glu Met Met Cys Gly Arg Leu Pro Phe Tyr Asn Gln 340 345 350 Asp His Glu Lys Leu Phe Glu Leu Ile Leu Met Glu Glu Ile Arg Phe 355 360 365 Pro Arg Thr Leu Gly Pro Glu Ala Lys Ser Leu Leu Ser Gly Leu Leu 370 375 380 Lys Lys Asp Pro Lys Gln Arg Leu Gly Gly Gly Ser Glu Asp Ala Lys 385 390 395 400 Glu Ile Met Gln His Arg Phe Phe Ala Gly Ile Val Trp Gln His Val 405 410 415 Tyr Glu Lys Lys Leu Ser Pro Pro Phe Lys Pro Gln Val Thr Ser Glu 420 425 430 Thr Asp Thr Arg Tyr Phe Asp Glu Glu Phe Thr Ala Gln Met Ile Thr 435 440 445 Ile Thr Pro Pro Asp Gln Asp Asp Ser Met Glu Cys Val Asp Ser Glu 450 455 460 Arg Arg Pro His Phe Pro Gln Phe Ser Tyr Ser Ala Ser Gly Thr Ala 465 470 475 480 <210> SEQ ID NO 104 <211> LENGTH: 379 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 104 Met Ala Ala Ala Ala Ala Gln Gly Gly Gly Gly Gly Glu Pro Arg Arg 1 5 10 15 Thr Glu Gly Val Gly Pro Gly Val Pro Gly Glu Val Glu Met Val Lys 20 25 30 Gly Gln Pro Phe Asp Val Gly Pro Arg Tyr Thr Gln Leu Gln Tyr Ile 35 40 45 Gly Glu Gly Ala Tyr Gly Met Val Ser Ser Ala Tyr Asp His Val Arg 50 55 60 Lys Thr Arg Val Ala Ile Lys Lys Ile Ser Pro Phe Glu His Gln Thr 65 70 75 80 Tyr Cys Gln Arg Thr Leu Arg Glu Ile Gln Ile Leu Leu Arg Phe Arg 85 90 95 His Glu Asn Val Ile Gly Ile Arg Asp Ile Leu Arg Ala Ser Thr Leu 100 105 110 Glu Ala Met Arg Asp Val Tyr Ile Val Gln Asp Leu Met Glu Thr Asp 115 120 125 Leu Tyr Lys Leu Leu Lys Ser Gln Gln Leu Ser Asn Asp His Ile Cys 130 135 140 Tyr Phe Leu Tyr Gln Ile Leu Arg Gly Leu Lys Tyr Ile His Ser Ala 145 150 155 160 Asn Val Leu His Arg Asp Leu Lys Pro Ser Asn Leu Leu Ile Asn Thr 165 170 175 Thr Cys Asp Leu Lys Ile Cys Asp Phe Gly Leu Ala Arg Ile Ala Asp 180 185 190 Pro Glu His Asp His Thr Gly Phe Leu Thr Glu Tyr Val Ala Thr Arg 195 200 205 Trp Tyr Arg Ala Pro Glu Ile Met Leu Asn Ser Lys Gly Tyr Thr Lys 210 215 220 Ser Ile Asp Ile Trp Ser Val Gly Cys Ile Leu Ala Glu Met Leu Ser 225 230 235 240 Asn Arg Pro Ile Phe Pro Gly Lys His Tyr Leu Asp Gln Leu Asn His 245 250 255 Ile Leu Gly Ile Leu Gly Ser Pro Ser Gln Glu Asp Leu Asn Cys Ile 260 265 270

Ile Asn Met Lys Ala Arg Asn Tyr Leu Gln Ser Leu Pro Ser Lys Thr 275 280 285 Lys Val Ala Trp Ala Lys Leu Phe Pro Lys Ser Asp Ser Lys Ala Leu 290 295 300 Asp Leu Leu Asp Arg Met Leu Thr Phe Asn Pro Asn Lys Arg Ile Thr 305 310 315 320 Val Glu Glu Ala Leu Ala His Pro Tyr Leu Glu Gln Tyr Tyr Asp Pro 325 330 335 Thr Asp Glu Pro Val Ala Glu Glu Pro Phe Thr Phe Ala Met Glu Leu 340 345 350 Asp Asp Leu Pro Lys Glu Arg Leu Lys Glu Leu Ile Phe Gln Glu Thr 355 360 365 Ala Arg Phe Gln Pro Gly Val Leu Glu Ala Pro 370 375 <210> SEQ ID NO 105 <211> LENGTH: 360 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 105 Met Ala Ala Ala Ala Ala Ala Gly Ala Gly Pro Glu Met Val Arg Gly 1 5 10 15 Gln Val Phe Asp Val Gly Pro Arg Tyr Thr Asn Leu Ser Tyr Ile Gly 20 25 30 Glu Gly Ala Tyr Gly Met Val Cys Ser Ala Tyr Asp Asn Val Asn Lys 35 40 45 Val Arg Val Ala Ile Lys Lys Ile Ser Pro Phe Glu His Gln Thr Tyr 50 55 60 Cys Gln Arg Thr Leu Arg Glu Ile Lys Ile Leu Leu Arg Phe Arg His 65 70 75 80 Glu Asn Ile Ile Gly Ile Asn Asp Ile Ile Arg Ala Pro Thr Ile Glu 85 90 95 Gln Met Lys Asp Val Tyr Ile Val Gln Asp Leu Met Glu Thr Asp Leu 100 105 110 Tyr Lys Leu Leu Lys Thr Gln His Leu Ser Asn Asp His Ile Cys Tyr 115 120 125 Phe Leu Tyr Gln Ile Leu Arg Gly Leu Lys Tyr Ile His Ser Ala Asn 130 135 140 Val Leu His Arg Asp Leu Lys Pro Ser Asn Leu Leu Leu Asn Thr Thr 145 150 155 160 Cys Asp Leu Lys Ile Cys Asp Phe Gly Leu Ala Arg Val Ala Asp Pro 165 170 175 Asp His Asp His Thr Gly Phe Leu Thr Glu Tyr Val Ala Thr Arg Trp 180 185 190 Tyr Arg Ala Pro Glu Ile Met Leu Asn Ser Lys Gly Tyr Thr Lys Ser 195 200 205 Ile Asp Ile Trp Ser Val Gly Cys Ile Leu Ala Glu Met Leu Ser Asn 210 215 220 Arg Pro Ile Phe Pro Gly Lys His Tyr Leu Asp Gln Leu Asn His Ile 225 230 235 240 Leu Gly Ile Leu Gly Ser Pro Ser Gln Glu Asp Leu Asn Cys Ile Ile 245 250 255 Asn Leu Lys Ala Arg Asn Tyr Leu Leu Ser Leu Pro His Lys Asn Lys 260 265 270 Val Pro Trp Asn Arg Leu Phe Pro Asn Ala Asp Ser Lys Ala Leu Asp 275 280 285 Leu Leu Asp Lys Met Leu Thr Phe Asn Pro His Lys Arg Ile Glu Val 290 295 300 Glu Gln Ala Leu Ala His Pro Tyr Leu Glu Gln Tyr Tyr Asp Pro Ser 305 310 315 320 Asp Glu Pro Ile Ala Glu Ala Pro Phe Lys Phe Asp Met Glu Leu Asp 325 330 335 Asp Leu Pro Lys Glu Lys Leu Lys Glu Leu Ile Phe Glu Glu Thr Ala 340 345 350 Arg Phe Gln Pro Gly Tyr Arg Ser 355 360 <210> SEQ ID NO 106 <211> LENGTH: 239 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 106 Met Ala His Ala Gly Arg Thr Gly Tyr Asp Asn Arg Glu Ile Val Met 1 5 10 15 Lys Tyr Ile His Tyr Lys Leu Ser Gln Arg Gly Tyr Glu Trp Asp Ala 20 25 30 Gly Asp Val Gly Ala Ala Pro Pro Gly Ala Ala Pro Ala Pro Gly Ile 35 40 45 Phe Ser Ser Gln Pro Gly His Thr Pro His Pro Ala Ala Ser Arg Asp 50 55 60 Pro Val Ala Arg Thr Ser Pro Leu Gln Thr Pro Ala Ala Pro Gly Ala 65 70 75 80 Ala Ala Gly Pro Ala Leu Ser Pro Val Pro Pro Val Val His Leu Thr 85 90 95 Leu Arg Gln Ala Gly Asp Asp Phe Ser Arg Arg Tyr Arg Arg Asp Phe 100 105 110 Ala Glu Met Ser Ser Gln Leu His Leu Thr Pro Phe Thr Ala Arg Gly 115 120 125 Arg Phe Ala Thr Val Val Glu Glu Leu Phe Arg Asp Gly Val Asn Trp 130 135 140 Gly Arg Ile Val Ala Phe Phe Glu Phe Gly Gly Val Met Cys Val Glu 145 150 155 160 Ser Val Asn Arg Glu Met Ser Pro Leu Val Asp Asn Ile Ala Leu Trp 165 170 175 Met Thr Glu Tyr Leu Asn Arg His Leu His Thr Trp Ile Gln Asp Asn 180 185 190 Gly Gly Trp Asp Ala Phe Val Glu Leu Tyr Gly Pro Ser Met Arg Pro 195 200 205 Leu Phe Asp Phe Ser Trp Leu Ser Leu Lys Thr Leu Leu Ser Leu Ala 210 215 220 Leu Val Gly Ala Cys Ile Thr Leu Gly Ala Tyr Leu Gly His Lys 225 230 235 <210> SEQ ID NO 107 <211> LENGTH: 99 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 107 Met Thr Ser Lys Leu Ala Val Ala Leu Leu Ala Ala Phe Leu Ile Ser 1 5 10 15 Ala Ala Leu Cys Glu Gly Ala Val Leu Pro Arg Ser Ala Lys Glu Leu 20 25 30 Arg Cys Gln Cys Ile Lys Thr Tyr Ser Lys Pro Phe His Pro Lys Phe 35 40 45 Ile Lys Glu Leu Arg Val Ile Glu Ser Gly Pro His Cys Ala Asn Thr 50 55 60 Glu Ile Ile Val Lys Leu Ser Asp Gly Arg Glu Leu Cys Leu Asp Pro 65 70 75 80 Lys Glu Asn Trp Val Gln Arg Val Val Glu Lys Phe Leu Lys Arg Ala 85 90 95 Glu Asn Ser <210> SEQ ID NO 108 <211> LENGTH: 107 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 108 Met Ala Arg Ala Ala Leu Ser Ala Ala Pro Ser Asn Pro Arg Leu Leu 1 5 10 15 Arg Val Ala Leu Leu Leu Leu Leu Leu Val Ala Ala Gly Arg Arg Ala 20 25 30 Ala Gly Ala Ser Val Ala Thr Glu Leu Arg Cys Gln Cys Leu Gln Thr 35 40 45 Leu Gln Gly Ile His Pro Lys Asn Ile Gln Ser Val Asn Val Lys Ser 50 55 60 Pro Gly Pro His Cys Ala Gln Thr Glu Val Ile Ala Thr Leu Lys Asn 65 70 75 80 Gly Arg Lys Ala Cys Leu Asn Pro Ala Ser Pro Ile Val Lys Lys Ile 85 90 95 Ile Glu Lys Met Leu Asn Ser Asp Lys Ser Asn 100 105 <210> SEQ ID NO 109 <211> LENGTH: 350 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 109 Met Ser Asn Ile Thr Asp Pro Gln Met Trp Asp Phe Asp Asp Leu Asn 1 5 10 15 Phe Thr Gly Met Pro Pro Ala Asp Glu Asp Tyr Ser Pro Cys Met Leu 20 25 30 Glu Thr Glu Thr Leu Asn Lys Tyr Val Val Ile Ile Ala Tyr Ala Leu 35 40 45 Val Phe Leu Leu Ser Leu Leu Gly Asn Ser Leu Val Met Leu Val Ile 50 55 60 Leu Tyr Ser Arg Val Gly Arg Ser Val Thr Asp Val Tyr Leu Leu Asn 65 70 75 80 Leu Ala Leu Ala Asp Leu Leu Phe Ala Leu Thr Leu Pro Ile Trp Ala 85 90 95 Ala Ser Lys Val Asn Gly Trp Ile Phe Gly Thr Phe Leu Cys Lys Val 100 105 110 Val Ser Leu Leu Lys Glu Val Asn Phe Tyr Ser Gly Ile Leu Leu Leu 115 120 125 Ala Cys Ile Ser Val Asp Arg Tyr Leu Ala Ile Val His Ala Thr Arg 130 135 140 Thr Leu Thr Gln Lys Arg His Leu Val Lys Phe Val Cys Leu Gly Cys 145 150 155 160 Trp Gly Leu Ser Met Asn Leu Ser Leu Pro Phe Phe Leu Phe Arg Gln 165 170 175 Ala Tyr His Pro Asn Asn Ser Ser Pro Val Cys Tyr Glu Val Leu Gly 180 185 190

Asn Asp Thr Ala Lys Trp Arg Met Val Leu Arg Ile Leu Pro His Thr 195 200 205 Phe Gly Phe Ile Val Pro Leu Phe Val Met Leu Phe Cys Tyr Gly Phe 210 215 220 Thr Leu Arg Thr Leu Phe Lys Ala His Met Gly Gln Lys His Arg Ala 225 230 235 240 Met Arg Val Ile Phe Ala Val Val Leu Ile Phe Leu Leu Cys Trp Leu 245 250 255 Pro Tyr Asn Leu Val Leu Leu Ala Asp Thr Leu Met Arg Thr Gln Val 260 265 270 Ile Gln Glu Ser Cys Glu Arg Arg Asn Asn Ile Gly Arg Ala Leu Asp 275 280 285 Ala Thr Glu Ile Leu Gly Phe Leu His Ser Cys Leu Asn Pro Ile Ile 290 295 300 Tyr Ala Phe Ile Gly Gln Asn Phe Arg His Gly Phe Leu Lys Ile Leu 305 310 315 320 Ala Met His Gly Leu Val Ser Lys Glu Phe Leu Ala Arg His Arg Val 325 330 335 Thr Ser Tyr Thr Ser Ser Ser Val Asn Val Ser Ser Asn Leu 340 345 350 <210> SEQ ID NO 110 <211> LENGTH: 360 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 110 Met Glu Asp Phe Asn Met Glu Ser Asp Ser Phe Glu Asp Phe Trp Lys 1 5 10 15 Gly Glu Asp Leu Ser Asn Tyr Ser Tyr Ser Ser Thr Leu Pro Pro Phe 20 25 30 Leu Leu Asp Ala Ala Pro Cys Glu Pro Glu Ser Leu Glu Ile Asn Lys 35 40 45 Tyr Phe Val Val Ile Ile Tyr Ala Leu Val Phe Leu Leu Ser Leu Leu 50 55 60 Gly Asn Ser Leu Val Met Leu Val Ile Leu Tyr Ser Arg Val Gly Arg 65 70 75 80 Ser Val Thr Asp Val Tyr Leu Leu Asn Leu Ala Leu Ala Asp Leu Leu 85 90 95 Phe Ala Leu Thr Leu Pro Ile Trp Ala Ala Ser Lys Val Asn Gly Trp 100 105 110 Ile Phe Gly Thr Phe Leu Cys Lys Val Val Ser Leu Leu Lys Glu Val 115 120 125 Asn Phe Tyr Ser Gly Ile Leu Leu Leu Ala Cys Ile Ser Val Asp Arg 130 135 140 Tyr Leu Ala Ile Val His Ala Thr Arg Thr Leu Thr Gln Lys Arg Tyr 145 150 155 160 Leu Val Lys Phe Ile Cys Leu Ser Ile Trp Gly Leu Ser Leu Leu Leu 165 170 175 Ala Leu Pro Val Leu Leu Phe Arg Arg Thr Val Tyr Ser Ser Asn Val 180 185 190 Ser Pro Ala Cys Tyr Glu Asp Met Gly Asn Asn Thr Ala Asn Trp Arg 195 200 205 Met Leu Leu Arg Ile Leu Pro Gln Ser Phe Gly Phe Ile Val Pro Leu 210 215 220 Leu Ile Met Leu Phe Cys Tyr Gly Phe Thr Leu Arg Thr Leu Phe Lys 225 230 235 240 Ala His Met Gly Gln Lys His Arg Ala Met Arg Val Ile Phe Ala Val 245 250 255 Val Leu Ile Phe Leu Leu Cys Trp Leu Pro Tyr Asn Leu Val Leu Leu 260 265 270 Ala Asp Thr Leu Met Arg Thr Gln Val Ile Gln Glu Thr Cys Glu Arg 275 280 285 Arg Asn His Ile Asp Arg Ala Leu Asp Ala Thr Glu Ile Leu Gly Ile 290 295 300 Leu His Ser Cys Leu Asn Pro Leu Ile Tyr Ala Phe Ile Gly Gln Lys 305 310 315 320 Phe Arg His Gly Leu Leu Lys Ile Leu Ala Ile His Gly Leu Ile Ser 325 330 335 Lys Asp Ser Leu Pro Lys Asp Ser Arg Pro Ser Phe Val Gly Ser Ser 340 345 350 Ser Gly His Thr Ser Thr Thr Leu 355 360

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