KR100961926B1 - 당뇨병성 망막병증 검출용 바이오 마커 조성물 및 진단키트 - Google Patents

당뇨병성 망막병증 검출용 바이오 마커 조성물 및 진단키트 Download PDF

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KR100961926B1
KR100961926B1 KR1020070087512A KR20070087512A KR100961926B1 KR 100961926 B1 KR100961926 B1 KR 100961926B1 KR 1020070087512 A KR1020070087512 A KR 1020070087512A KR 20070087512 A KR20070087512 A KR 20070087512A KR 100961926 B1 KR100961926 B1 KR 100961926B1
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김영수
유형곤
김상진
김태오
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서울대학교산학협력단
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Abstract

본 발명은 서열번호 1 내지 105의 아미노산 서열로 이루어진 단백질로부터 1 종 이상 선택된 단백질을 포함하는 당뇨병성 망막병증(diabetic retinopathy) 검출용 바이오 마커 조성물을 제공한다. 또한, 본 발명은 서열번호 1 내지 105의 아미노산 서열로 이루어진 단백질로부터 1 종 이상 선택된 단백질과 특이적으로 결합하는 분자를 포함하는, 당뇨병성 망막병증(diabetic retinopathy) 진단 키트를 제공한다.
서열번호 1 내지 105의 아미노산 서열을 갖는 단백질은 PDR 환자에서 특이적으로 과량 발현되는 것으로 새롭게 밝혀진 단백질로서, 당뇨병성 망막병증을 검출할 수 있는 바이오 마커로서 사용될 수 있다. 따라서, 상기 바이오 마커는 당뇨병성 망막병증과 같은 유리체망막(vitreoretinal) 질환을 연구하는데 기초적인 정보를 제공할 수 있다. 특히, 상기 새롭게 밝혀진 단백질은 해당 단백질과 특이적으로 결합하는 분자, 예를 들어 모노클로날 항체 등과 함께 당뇨병성 망막병증의 진단을 위한 진단 키트로 제작될 수 있다.
당뇨병성 망막병증, 바이오 마커

Description

당뇨병성 망막병증 검출용 바이오 마커 조성물 및 진단 키트{Biomarker composition for detecting diabetic retinopathy and diagnostic kit therefor}
본 발명은 당뇨병성 망막병증(diabetic retinopathy) 검출을 위한 바이오 마커 조성물; 및 당뇨병성 망막병증 진단용 키트에 관한 것이다.
당뇨병(diabetes mellitus)은 인슐린 분비 감소, 글루코오즈 사용 감소 또는 글루코오즈 생성 증가로부터 야기되는 높은 혈중 글루코오즈에 의해 특징되는 대사성 질환이다. 미국에서는 적어도 2000 만명의 당뇨병 환자가 있다 [1]. 당뇨병은 심각한 혈관성 증상들로 전개될 수 있으며, 여기에는 관상 심장 질환(coronary heart disease), 뇌혈관 질환(cerebrovascular disease), 및 말초 혈관 질환 등과 같은 대혈관성 증상(macrovascular complications) 및 당뇨병성 망막병증(diabetic retinopathy), 신장병증(nephropathy), 및 신경병증(neuropathy) 등과 같은 미세혈관성 증상(microvascular complications)이 포함된다.
당뇨병성 망막병증(Diabetic retinopathy, DR)은 15년 이상의 병력을 가진 당뇨병 환자의 4분의 3에서 발생하며, 미국에서 매년 12,000 내지 24,000의 새로운 시각 상실의 원인이 됨으로써 당뇨병은 성인(20 내지 74세)의 시각상실 중 가장 높 은 빈도의 원인이 되고 있다 [1]. 당뇨병성 망막병증에 있어서의 병인적 변화는, 망막 혈액 흐름 장애, 혈관 투과성 증가, 혈액-망막 장벽의 파괴, 및 국소 저산소증을 야기하는 모세혈관 폐색(capillary occlusion) 등과 같은 망막 혈관 이상을 포함한다 [3-6]. 또한, 망막 저산소증이 진행됨에 따라, 망막 혈관신생을 촉진하는 혈관신생 인자들이 유도된다.
증식성 당뇨병성 망막병증(proliferative diabetic retinopathy, PDR)은 유리체 공동(vitreous cavity)으로의 새로운 혈관 성장에 관여하고, 이어서 혈관섬유(fibrovascular) 증식, 망막 분리, 및 망막 출혈에 관여하여, 결국 시각상실을 야기한다. 범망막 광응고(panretinal photocoagulation) 및 유리체절제술(vitrectomy)에 의해 시각상실을 줄일 수는 있으나, 당뇨병성 망막병증에 의해 야기되는 시각적 손상은 높은 관심을 받고 있다 [7, 8].
많은 연구에 의해 PDR의 발병기전과 관련된 인자, 예를 들어, 혈관 내피 성장 인자와 같은 혈관신생 인자[9-12], 안지오텐신-전환 효소[13], 인슐린-유사 성장 인자[14], 안지오포이에틴[15], 에리스로포이에틴[16], 태반 성장 인자[17], 및 글리케이션(advanced glycation)의 최종 생성물[18], 및 색소 상피 유도 인자(pigment epithelium derived factor)와 같은 항-혈관신생 인자[19-21]가 동정되었다. 그러나, 대부분의 기존 연구들은 표적 단백질 세트, 특히 혈관신생 및 세포 증식에 관여하는 분자들에 초점을 두고 있었으므로, 전체적인 유리체액(vitreous humor) 단백질들에 있어서의 변화를 측정/평가하고 또한 PDR 발명기전의 새로운 마커를 동정하는 것이 곤란하다.
2차원 겔 전기영동(two-dimensional gel electrophoresis, 2-DE) 및 질량 분석(mass spectrometry, MS)에 있어서의 최근의 진보에 의하여 유리체 단백질 프로파일을 탐색하는 것이 가능할 수 있다 [22-24]. 2-DE 및 MALDI-TOF (atrix-assisted laser desorption ionization-time of flight) MS를 사용한 본 발명자들의 종래의 연구에서, 본 발명자들은 PDR 유리체 단백질 프로파일을 구축하였으며, PDR의 발명에 관여할 것으로 여겨지는 8개의 단백질을 동정한 바 있다 [25].
종래기술의 문헌정보
[문헌 1] CDC, National Diabetes Fact Sheet: General information and National Estimates on Diabetes in the United States. US Department of Health and Human Services, Centers for Disease Control and Prevention , Atlanta , GA(2005)
[문헌 2] Klein, R., Klein, B. E., Moss, S. E., Cruickshanks, K. J., The Wisconsin Epidemiologic Study of Diabetic Retinopathy: XVII. The 14-year incidence and progression of diabetic retinopathy and associated risk factors in type 1 diabetes. Ophthalmology 1998, 105, 1801-1815.
[문헌 3] Schroder, S., Palinski, W., Schmid-Schonbein, G. W., Activated monocytes and granulocytes, capillary nonperfusion, and neovascularization in diabetic retinopathy. The American journal of pathology 1991, 139, 81-100.
[문헌 4] Krogsaa, B., Lund-Andersen, H., Mehlsen, J., Sestoft, L., Larsen, J., The blood-retinal barrier permeability in diabetic patients. Acta ophthalmologica 1981, 59, 689-694.
[문헌 5] Bursell, S. E., Clermont, A. C., Kinsley, B. T., Simonson, D. C., et al., Retinal blood flow changes in patients with insulin-dependent diabetes mellitus and no diabetic retinopathy. Investigative ophthalmology & visual science 1996, 37, 886-897.
[문헌 6] Gardner, T. W., Antonetti, D. A., Barber, A. J., LaNoue, K. F., Levison, S. W., Diabetic retinopathy: more than meets the eye. Survey of ophthalmology 2002, 47 Suppl 2, S253-262.
[문헌 7] Ferris, F. L., Davis, M., Early Treatment Diabetic Retinopathy Study Research Group. Early Treatment Diabetic Retinopathy Study Research Group No. 1: Photocoagulation for diabetic macular edema. Early treatment diabetic retinopathy study report no. 1: photocoagulation for diabetic macular edema. Arch. Ophthalmol . 1985, 103, 1796-1806.
[문헌 8] Lewis, H., Abrams, G. W., Blumenkranz, M. S., Campo, R. V., Vitrectomy for diabetic macular traction and edema associated with posterior hyaloidal traction. Ophthalmology 1992, 99, 753-759.
[문헌 9] Witmer, A. N., Blaauwgeers, H. G., Weich, H. A., Alitalo, K., et al., Altered expression patterns of VEGF receptors in human diabetic retina and in experimental VEGF-induced retinopathy in monkey. Investigative ophthalmology & visual science 2002, 43, 849-857.
[문헌 10] Pe'er, J., Folberg, R., Itin, A., Gnessin, H., et al., Upregulated expression of vascular endothelial growth factor in proliferative diabetic retinopathy. The British journal of ophthalmology 1996, 80, 241-245.
[문헌 11] Mathews, M. K., Merges, C., McLeod, D. S., Lutty, G. A., Vascular endothelial growth factor and vascular permeability changes in human diabetic retinopathy. Investigative ophthalmology & visual science 1997, 38, 2729-2741.
[문헌 12] Witmer, A. N., Vrensen, G. F., Van Noorden, C. J., Schlingemann, R. O., Vascular endothelial growth factors and angiogenesis in eye disease. Progress in retinal and eye research 2003, 22, 1-29.
[문헌 13] Kida, T., Ikeda, T., Nishimura, M., Sugiyama, T., et al., Renin-angiotensin system in proliferative diabetic retinopathy and its gene expression in cultured human muller cells. Japanese journal of ophthalmology 2003, 47, 36-41.
[문헌 14] Guidry, C., Feist, R., Morris, R., Hardwick, C. W., Changes in IGF activities in human diabetic vitreous. Diabetes 2004, 53, 2428-2435.
[문헌 15] Ohashi, H., Takagi, H., Koyama, S., Oh, H., et al., Alterations in expression of angiopoietins and the Tie-2 receptor in the retina of streptozotocin induced diabetic rats. Molecular vision 2004, 10, 608-617.
[문헌 16] Watanabe, D., K., S., Erythropoietin as a retinal angiogenic factor in proliferative diabetic retinopathy. The New England journal of medicine 2005, 353, 782-792.
[문헌 17] Mitamura, Y., Tashimo, A., Nakamura, Y., Tagawa, H., et al., Vitreous levels of placenta growth factor and vascular endothelial growth factor in patients with proliferative diabetic retinopathy. Diabetes care 2002, 25, 2352.
[문헌 18] Matsumoto, Y., Takahashi, M., Chikuda, M., Arai, K., Levels of mature cross-links and advanced glycation end product cross-links in human vitreous. Japanese journal of ophthalmology 2002, 46, 510-517.
[문헌 19] Dawson, D. W., Volpert, O. V., Gillis, P., Crawford, S. E., et al., Pigment epithelium-derived factor: a potent inhibitor of angiogenesis. Science ( New York , N.Y 1999, 285, 245-248.
[문헌 20] Duh, E. J., Yang, H. S., Suzuma, I., Miyagi, M., et al., Pigment epithelium-derived factor suppresses ischemia-induced retinal neovascularization and VEGF-induced migration and growth. Investigative ophthalmology & visual science 2002, 43, 821-829.
[문헌 21] Spranger, J., Osterhoff, M., Reimann, M., Mohlig, M., et al., Loss of the antiangiogenic pigment epithelium-derived factor in patients with angiogenic eye disease. Diabetes 2001, 50, 2641-2645.
[문헌 22] Nakanishi, T., Koyama, R., Ikeda, T., Shimizu, A., Catalogue of soluble proteins in the human vitreous humor: comparison between diabetic retinopathy and macular hole. Journal of chromatography 2002, 776, 89-100.
[문헌 23] Ouchi, M., West, K., Crabb, J. W., Kinoshita, S., Kamei, M., Proteomic analysis of vitreous from diabetic macular edema. Experimental eye research 2005, 81, 176-182.
[문헌 24] Yamane, K., Minamoto, A., Yamashita, H., Takamura, H., et al., Proteome analysis of human vitreous proteins. Mol Cell Proteomics 2003, 2, 1177-1187.
[문헌 25] Kim, S. J., Kim, S., Park, J., Lee, H. K., et al., Differential expression of vitreous proteins in proliferative diabetic retinopathy. Current eye research 2006, 31, 231-240.
본 발명자들은 PDR 을 검출할 수 있는 바이오 마커 단백질을 동정하기 위하여, PDR 발병 기전에 관여하는 전체적인 단백질을 검색하였다. 특히, 본 발명자들은 PDR 발명기전에 관여하는 신규의 바이오 마커를 검색하기 위하여, 낮은 수준으로 존재하는 미량 단백질(low abundance proteins)을 검색하였다. 그 결과, 531개 단백질이 유리체 프로테옴에서 동정되었으며, 이 중, 240개 단백질이 신규로 동정되었다. 상기 새롭게 동정된 240개 단백질 중, 105 개의 단백질이 PDR 환자의 유리체에서 특이적으로 과량 발현된다는 것을 발견하였다.
따라서, 본 발명은 PDR 환자의 유리체에서 특이적으로 과량 발현되는 것으로 밝혀진 상기 105개의 신규 단백질을 포함하는 당뇨병성 망막병증(diabetic retinopathy) 검출용 바이오 마커 조성물을 제공하는 것을 목적으로 한다.
또한, 본 발명은 상기 단백질과 특이적으로 결합하는 분자를 포함하는, 당뇨병성 망막병증(diabetic retinopathy) 진단 키트를 제공하는 것을 목적으로 한다.
본 발명의 일 태양에 따라, 서열번호 1 내지 105의 아미노산 서열로 이루어진 단백질로부터 1 종 이상 선택된 단백질을 포함하는 당뇨병성 망막병증(diabetic retinopathy) 검출용 바이오 마커 조성물이 제공된다.
본 발명의 바이오 마커 조성물에 있어서, 상기 단백질은 서열번호 4, 5, 8, 15, 19, 27, 30, 32, 33, 36, 38, 39, 40, 41, 42, 45, 46, 47, 48, 49, 51, 52, 53, 55, 56, 59, 60, 62, 66, 67, 68, 69, 71, 74, 78, 83, 86, 88, 89, 91, 95, 96, 97, 98, 99, 100, 및 105의 아미노산 서열로 이루어진 단백질로부터 1 종 이상 선택되는 것이 바람직하다. 또한, 본 발명의 바이오 마커 조성물은 검체로서 혈액 또는 뇨(urine)를 바람직하게 사용할 수 있다.
본 발명의 다른 태양에 따라, 서열번호 1 내지 105의 아미노산 서열로 이루어진 단백질로부터 1 종 이상 선택된 단백질과 특이적으로 결합하는 분자를 포함하는, 당뇨병성 망막병증(diabetic retinopathy) 진단 키트가 제공된다.
상기 분자는 모노클로날 항체, 폴리클로날 항체, 기질, 리간드, 또는 보조인자(cofactor) 등 일 수 있으며, 상기 단백질은 서열번호 4, 5, 8, 15, 19, 27, 30, 32, 33, 36, 38, 39, 40, 41, 42, 45, 46, 47, 48, 49, 51, 52, 53, 55, 56, 59, 60, 62, 66, 67, 68, 69, 71, 74, 78, 83, 86, 88, 89, 91, 95, 96, 97, 98, 99, 100, 및 105의 아미노산 서열로 이루어진 단백질로부터 1 종 이상 선택된 것을 바람직하게 사용할 수 있다. 또한, 본 발명의 진단 키트는 검체로서 혈액 또는 뇨(urine)를 바람직하게 사용할 수 있다.
서열번호 1 내지 105의 아미노산 서열을 갖는 단백질은 PDR 환자에서 특이적으로 과량 발현되는 것으로 새롭게 밝혀진 단백질로서, 당뇨병성 망막병증(diabetic retinopathy)을 검출할 수 있는 바이오 마커로서 사용될 수 있다. 따라서, 상기 바이오 마커는 당뇨병성 망막병증과 같은 유리체망막(vitreoretinal) 질환을 연구하는데 기초적인 정보를 제공할 수 있다. 특히, 상기 새롭게 밝혀진 단백질은 해당 단백질과 특이적으로 결합하는 분자, 예를 들어 모노클로날 항체 등과 함께 당뇨병성 망막병증의 진단을 위한 진단 키트로 제작될 수 있다.
본 발명은 서열번호 1 내지 105의 아미노산 서열로 이루어진 단백질로부터 1 종 이상 선택된 단백질을 포함하는 당뇨병성 망막병증(diabetic retinopathy, PDR) 검출용 바이오 마커 조성물을 포함한다.
본 발명자들은 단백체학적 방법(proteomic methods), 즉, IS/2-DE/MALDI-MS, 나노 LC-MALDI-MS/MS, 및 나노 LC-ESI-MS/MS을 사용하여 유리체 단백체(vitreous proteome)의 성분들을 동정하였다. 나노 LC-MALDI-MS/MS, 및 나노 LC-ESI-MS/MS에 의해 동정된 단백질은 Trans-Proteomic Pipeline (TPP, http://www.proteomecenter.org/)을 사용하여 검증하였으며, Trans-Proteomic Pipeline에는 동형체(isoforms) 및 상동성(homologous) 단백질들이 대표적인 오르소로그(orthologues)로 그룹화되어 있다. 본 발명자들은 알부민/IgG 제거된 PDR 샘플, 비-알부민/IgG 제거된 PDR 샘플, 및 황반(macular hole, MH) 유리체 샘플에 대한 LC-MS/MS 분석을 수행하여, PDR 발병과 관련된 총 단백질을 검색하였으며, 531 개의 단백질을 동정하였다 (도 6a 내지 도 6g 참조). 상기 531개 단백질에 대한 데이터베이스 검색 결과, 240개 단백질이 PDR 발병과 관련되는 것으로 새롭게 밝혀졌으며, 이 중 하기 표 1a 내지 표 1d에 나타낸 105 개의 단백질은 PDR 환자의 유리체에서 특이적으로 과량 발현된다는 것이 새롭게 밝혀 졌다.
서열번호 혈장 프로테옴에서 검출 단백질명 IPI accession number 비고(**)
1 101 KDA PROTEIN IPI00760855 A
2 13 kDa protein IPI00743473 A
3 14-3-3 protein epsilon IPI00000816 A
4 * 16 kDa protein IPI00218733 A
5 * 184 KDA PROTEIN IPI00303313 A
6 57 kDa protein IPI00383111 A
7 97 KDA PROTEIN IPI00794184 A
8 * Adiponectin precursor IPI00020019 A
9 ADP-ribosylation factor 1 IPI00215914 A
10 ALPHA3A IPI00377045 A
11 ANNEXIN A2 ISOFORM 1 IPI00418169 A
12 Beta-hexosaminidase beta chain precursor IPI00012585 A
13 Biglycan precursor IPI00010790 A
14 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B IPI00005592 A
15 * CALMODULIN-LIKE PROTEIN 5 IPI00021536 A
16 CD59 glycoprotein precursor IPI00011302 A
17 CDNA FLJ25678 fis, clone TST04067, highly similar to PURINE NUCLEOSIDE PHOSPHORYLASE IPI00017672 A
18 CDNA FLJ41981 fis, clone SMINT2011888, highly similar to Protein Tro alpha1 H,myeloma IPI00784830 A
19 * Cholinesterase precursor IPI00025864 A
20 Cofilin-1 IPI00012011 A
21 Corneodesmosin precursor IPI00386809 A
22 Dermatopontin precursor IPI00292130 A
23 E3 UBIQUITIN-PROTEIN LIGASE HECTD1 IPI00328911 A
24 Endothelial protein C receptor precursor IPI00009276 A
25 FERRITIN HEAVY CHAIN IPI00554521 A
26 FERRITIN LIGHT POLYPEPTIDE VARIANT IPI00796538 A
27 * Fetuin-B precursor IPI00005439 A
28 FIBRONECTIN 1 ISOFORM 4 PREPROPROTEIN IPI00414283 A
29 Fructose-bisphosphate aldolase C IPI00418262 A
30 * Gamma-glutamyl hydrolase precursor IPI00023728 A
서열번호 혈장 프로테옴에서 검출 단백질명 IPI accession number 비고(**)
31 Gastrokine-1 precursor IPI00021342 A
32 * Growth/differentiation factor 8 precursor IPI00023751 A
33 * Hepatocyte growth factor activator precursor IPI00029193 A
34 Hornerin IPI00398625 A
35 Hypoxanthine-guanine phosphoribosyltransferase IPI00218493 A
36 * Intercellular adhesion molecule 2 precursor IPI00009477 A
37 Isoform 1 of Arginase-1 IPI00291560 A
38 * Isoform 1 of Contactin-4 precursor IPI00178854 A
39 * Isoform 1 of C-reactive protein precursor IPI00022389 A
40 * Isoform 1 of Ficolin-3 precursor IPI00293925 A
41 * Isoform 1 of Mannan-binding lectin serine protease 2 precursor IPI00294713 A
42 * Isoform 1 of Multiple epidermal growth factor-like domains 8 IPI00027310 A
43 Isoform 1 of Phosphatidylinositol-glycan-specific phospholipase D precursor IPI00299503 A
44 ISOFORM 1 OF PHOSPHOLIPID TRANSFER PROTEIN PRECURSOR IPI00643034 A
45 * Isoform 1 of Plexin domain-containing protein 2 precursor IPI00044369 A
46 * Isoform 1 of Probable helicase senataxin IPI00142538 A
47 * Isoform A of Proteoglycan-4 precursor IPI00024825 A
48 * Kallistatin precursor IPI00328609 A
49 * Lipopolysaccharide-binding protein precursor IPI00032311 A
50 Lithostathine 1 alpha precursor IPI00009027 A
51 * Macrophage colony-stimulating factor 1 receptor precursor IPI00011218 A
52 * MAN1A1 PROTEIN IPI00291641 A
53 * MIMECAN PRECURSOR IPI00025465 A
54 MUCIN-5B PRECURSOR IPI00384897 A
55 * Multimerin-2 precursor IPI00015525 A
56 * Myocilin precursor IPI00019190 A
57 Myoglobin IPI00217493 A
58 Neurexin 3-alpha IPI00216728 A
59 * Nidogen-2 precursor IPI00028908 A
60 * PEPTIDYL-PROLYL CIS-TRANS ISOMERASE C IPI00024129 A
서열번호 혈장 프로테옴에서 검출 단백질명 IPI accession number 비고(**)
61 Phosphatidylethanolamine-binding protein 1 IPI00219446 A
62 * Pregnancy zone protein precursor IPI00025426 A
63 Protein DJ-1 IPI00298547 A
64 Pseudogene candidate IPI00454869 A
65 Rho GDP-dissociation inhibitor 2 IPI00003817 A
66 * Serpin B4 IPI00010303 A
67 * SUPEROXIDE DISMUTASE [MN], MITOCHONDRIAL PRECURSOR IPI00022314 A
68 * Thioredoxin IPI00216298 A
69 * Thyroxine-binding globulin precursor IPI00292946 A
70 TRIOSEPHOSPHATE ISOMERASE 1 VARIANT IPI00465028 A
71 * UNCHARACTERIZED PROTEIN C7ORF24 IPI00031564 A
72 V1-17 protein IPI00045547 A
73 V1-5 protein (Fragment) IPI00553215 A
74 * von Willebrand factor precursor IPI00023014 A
75 WSB-1 ISOFORM IPI00383777 A
76 10 kDa protein IPI00740756 C
77 25 kDa protein IPI00448800 C
78 * 272 KDA PROTEIN IPI00219299 C
79 330 kDa protein IPI00163866 C
80 3'-5' exoribonuclease CSL4 homolog IPI00032823 C
81 ACF7 PROTEIN IPI00183169 C
82 Actin, aortic smooth muscle IPI00008603 C
83 * ATP-binding cassette, sub-family A, member 2 isoform a IPI00307592 C
84 BONE MORPHOGENETIC PROTEIN RECEPTOR TYPE IA PRECURSOR IPI00005731 C
85 CDNA: FLJ21459 fis, clone COL04714 IPI00001606 C
86 * CENTROMERE PROTEIN F IPI00027157 C
87 CRYPTOCHROME-1 IPI00002540 C
88 * Dpy-19-like protein 1 IPI00007461 C
89 * EXOCYST COMPLEX COMPONENT 8 IPI00028264 C
90 ISOFORM 1 OF ALANINE AMINOTRANSFERASE 2 IPI00152432 C
서열번호 혈장 프로테옴에서 검출 단백질명 IPI accession number 비고(**)
91 * ISOFORM 1 OF GRIP AND COILED-COIL DOMAIN-CONTAINING PROTEIN 2 IPI00005631 C
92 ISOFORM 1 OF PROBABLE E3 UBIQUITIN-PROTEIN LIGASE HERC4 IPI00333067 C
93 ISOFORM 1 OF TRANSFORMATION/TRANSCRIPTION DOMAIN-ASSOCIATED PROTEIN IPI00069084 C
94 Isoform 1 of Uncharacterized protein C9orf84 IPI00658203 C
95 * ISOFORM 2 OF CROSSOVER JUNCTION ENDONUCLEASE EME1 IPI00073193 C
96 * ISOFORM 4 OF NESPRIN-1 IPI00247295 C
97 * Junctional adhesion molecule A precursor IPI00001754 C
98 * Mucin 5 (Fragment) IPI00103397 C
99 * POTASSIUM/SODIUM HYPERPOLARIZATION-ACTIVATED CYCLIC NUCLEOTIDE-GATED CHANNEL 1 IPI00031506 C
100 * PROTEIN BASSOON IPI00020153 C
101 SIMILAR TO GENERAL TRANSCRIPTION FACTOR II-I REPEAT DOMAIN-CONTAINING PROTEIN 1 (GTF2I REPEAT DOMAIN-CONTAINING PROTEIN 1) (MUSCLE TFII-I REPEAT DOMAIN-CONTAINING PROTEIN 1) (GENERAL TRANSCRIPTION FACTOR III) (SLOW-MUSCLE-FIBER ENHANCER BINDING PRO IPI00736974 C
102 Structural maintenance of chromosomes protein 1B IPI00479260 C
103 Thyroid hormone receptor-associated protein 2 IPI00400834 C
104 UNCHARACTERIZED PROTEIN C22ORF30 IPI00643747 C
105 * Utrophin IPI00009329 C
*: 혈장 프로테옴에서 검출됨
**:
A - 알부민/IgG 제거된 PDR 샘플에서만 발현(도 4의 C의 벤다이어그램 참조)
B - 알부민/IgG 제거된 PDR 샘플 및 비-알부민/IgG 제거된 PDR 샘플 모두에서 발현(도 4의 C의 벤다이어그램 참조)
C: 비-알부민/IgG 제거된 PDR 샘플에서만 발현(도 4의 C의 벤다이어그램 참조)
본 명세서에서, "서열번호 1 내지 105의 아미노산 서열로 이루어진 단백질로부터 1종 이상 선택된 단백질"이라 함은 서열번호 1 내지 105의 아미노산 서열 중에서 1종 이상 선택된 아미노산 서열을 가지는 단백질(들)을 말하며, 상기 "단백질(들)" 이라 함은 각각의 서열번호 1 내지 105의 아미노산의 전서열(full sequence) 뿐만 아니라, 그의 단편(fragments)을 포함하는 것으로 이해되어야 한다.
상기 본 발명의 바이오 마커 조성물은 인간의 조직 또는 체액 등의 검체에서 서열번호 1 내지 105의 아미노산 서열을 갖는 단백질을 검출하는데 사용할 수 있다. 특히 인간의 혈액이나 뇨를 검체로서 사용하는 경우 윤리성의 문제를 회피할 수 있으므로, 본 발명의 바이오 마커 조성물은 혈장 중에도 특이적으로 과량 발현되는 단백질을 포함하는 것이 바람직하다. 따라서, 본 발명의 PDR 검출용 바이오 마커 조성물은 혈장 중에도 특이적으로 과량 발현되는 것으로 밝혀진 단백질 즉, 서열번호 4, 5, 8, 15, 19, 27, 30, 32, 33, 36, 38, 39, 40, 41, 42, 45, 46, 47, 48, 49, 51, 52, 53, 55, 56, 59, 60, 62, 66, 67, 68, 69, 71, 74, 78, 83, 86, 88, 89, 91, 95, 96, 97, 98, 99, 100, 및 105의 아미노산 서열로 이루어진 단백질로부터 1 종 이상 선택된 단백질을 포함하는 것이 바람직하다.
본 발명의 바이오 마커 조성물에 있어서, 바이오 마커의 검출은 인간의 조직 또는 체액으로부터 이차원(2-D) 전기영동으로 바이오 마커 단백질의 존재를 직접 검출하거나, 인간의 조직 또는 체액을 본 발명의 항체와 접촉시켜 항원항체반응을 통해 바이오 마커 단백질의 존재를 간접적으로 확인함으로써 수행할 수 있다. 항원항체반응으로서, 면역분석법은 효소면역측정법 (ELISA, Coated tube), 항체결합 마그네틱 입자를 이용한 마그네틱 입자법, 항체결합 라텍스를 이용한 라텍스 입자법 등을 포함한다.
본 발명은 서열번호 1 내지 105의 아미노산 서열로 이루어진 단백질로부터 1 종 이상 선택된 단백질과 특이적으로 결합하는 분자를 포함하는, 당뇨병성 망막병증(proliferative diabetic retinopathy) 진단 키트를 포함한다.
상기 분자는 상기 단백질에 특이적으로 결합하는 항체, 기질, 리간드, 또는 보조인자(cofactor)일 수 있으며, 바람직하게는 폴리클로날 또는 모노클로날 항체, 더욱 바람직하게는 모노클로날 항체이다.
폴리클로날 항체는 당업자에 알려진 방법에 따라 면역원인 바이오 마커 단백질 또는 그 단편을 외부 숙주에 주사함으로써 제조될 수 있다. 외부 숙주는 마우스, 래트, 양, 토끼와 같은 포유동물을 포함한다. 면역원은 근내, 복강내 또는 피하 주사방법으로 주사되며, 일반적으로 항원성을 증가시키기 위한 보조제(adjuvant)와 함께 투여된다. 외부숙주로부터 정기적으로 혈청을 채취하여 향상된 역가 및 항원에 대한 특이성을 보이는 혈청을 수거하거나 이로부터 항체를 분리정제한다.
모노클로날 항체는 당업자에 알려진 융합에 의한 불멸화된 세포주 생성기술(Koeher and Milstein (1975) Nature, 256:495))에 의해 제조될 수 있다. 예를 들어, 서열번호 1 내지 105의 아미노산 서열을 갖는 단백질을 마우스에 면역화시키거나 펩타이드를 합성하여 소혈청 알부민과 결합시켜 마우스에 면역화시킨다. 마우스에서 분리된 항원-생산 B 임파구를 인간 또는 마우스의 미엘로마와 융합하여 불멸화된 하이브리도마를 생성하며, 이 하이브리도마 세포를 가지고 간접적인 엘라지져(ELISA)방법을 사용하여 모노클노날 항체의 생성여부를 알아보고 양성 클론을 택하여 배양한 후 항체를 분리정제하거나 쥐의 복강에 주입한 후 복수를 채취함으로써, 모노클로날 항체를 제조할 수 있다.
상기한 바와 같이, 인간의 혈액이나 뇨를 검체로서 사용하는 경우 윤리성의 문제를 회피할 수 있으므로 본 발명에 따른 진단 키트는 혈장 중에도 특이적으로 과량 발현되는 단백질과 특이적으로 결합하는 분자를 포함하는 것이 바람직하며, 상기 단백질은 서열번호 4, 5, 8, 15, 19, 27, 30, 32, 33, 36, 38, 39, 40, 41, 42, 45, 46, 47, 48, 49, 51, 52, 53, 55, 56, 59, 60, 62, 66, 67, 68, 69, 71, 74, 78, 83, 86, 88, 89, 91, 95, 96, 97, 98, 99, 100, 및 105의 아미노산 서열로 이루어진 단백질로부터 선택될 수 있다.
또한, 본 발명의 진단 키트는 검체로서 혈액 또는 뇨(urine)를 바람직하게 사용할 수 있다.
이하, 본 발명을 실시예를 통하여 더욱 상세히 설명한다. 그러나, 하기 실시예는 본 발명을 예시하기 위한 것으로, 본 발명이 이들 실시예에 의해 제한되는 것은 아니다.
실시예
1. 시험방법
(1) 환자 및 유리체 수거
황반 부위를 포함한 견인성 망막 박리(tractional retinal detachment) 수술 과정에서, 8명의 PDR 환자의 눈으로부터 2-DE 시험용 비희석된 유리체 샘플 및 11명의 PDR 환자의 눈으로부터 LC-MS/MS 시험용 비희석된 유리체 샘플을 얻었다. 넓은 망막 부위에서 활성 혈관신생 막을 나타내는 환자만을 포함시켰으며, 육안 유리체 출혈(gross vitreous hemorrhage) 또는 최근의 유리체 출혈 병력, 이전의 안구 수술(백내장 수술을 포함), 또는 포도막염과 같은 다른 안구 질환을 갖는 환자들은 배제하였다. 비-당뇨병 환자로부터의 대조군 샘플을 얻기 위하여, 작은 특발성 황반(idiopathic macular hole, MH)을 갖는 14개의 안구로부터 유리체 샘플을 얻었다 (표 2 참조).
샘플 세트
(환자 수)		 평균 나이
(범위)		 평균 농도: μg/μl
(범위)
2-DE 용 PDR
(n=8)		 62.5
(37-72)		 5.6
(3.3-7.5)
LC-MS/MS 용 PDR
(n=11)		 56.0
(52-73)		 6.4
(2.6-9.7)
LC-MS/MS 용 MH
(n=14)		 63.0
(45-71)		 0.43
(0.10-1.21)
MH는 유리체 중심 견인(vitreofoveal traction)의 결과로 진행되는 것으로 나타나는 것으로 알려져 있으므로, MH 유리체 샘플은 비-당뇨병 대조군으로 간주하였다. 경비한 병리학적 증상으로 인한 기타의 안구 질환을 갖는 환자도 또한 배제하였다. 서울 대학교 의과대학의 기관윤리위원회에 의해 승인된 프로토콜에 따라, 모든 환자는 본 연구에 참여하기 전에 설명후 동의(informed consent)를 받았다. 본 연구에 사용된 모든 프로토콜은 헬싱키 선언(Declaration of Helsinki)의 내용에 충분히 따른 것이다.
비희석된 유리체 샘플(0.5 - 0.8 ml)을 Millennium microsurgical system (Bausch & Lomb, Rochester, NY)을 사용하여 수행된 국부 평면 유리체절제술(pars plana vitrectomies)의 초기에 얻었다. 안압을 유지하기 위하여, 공막(sclera)을 만입시키면서(indented) 유리체를 1.0 ml 시린지에 연결된 유리체 커터(vitreous cutter)로 천천히 제거하였다. 수확된 유리체 샘플을 시험관에 모으고, 즉시 얼음에 넣고, -70 ℃에 보관하였다.
(2) 유리체 샘플의 준비
PDR 및 MH 대조군 샘플을 로딩된 모든 샘플이 완전히 필터를 통과할 때까지 0.22 μm GV DURAPORE filter (Millipore company, Carrigtwohill, Co. Cork, Ireland)을 사용하여 15,000 g로 여과/원심분리하였다. 단백질 농도는 Bio-Rad protein assay reagents (Bio-Rad Laboratories, Hercules, CA)를 사용하여 측정하였다. PDR 샘플의 단백질 농도는 대조군의 단백질 농도에 비하여 높았다 (약 10 배 높다; PDR 샘플 2.0∼10.0 μg/μl, 대조군 샘플 0.1∼1.2 μg/μl). PDR 및 MH 환자로부터 얻은 상기 여과/원심분리된 유리체 샘플을 수거한 후, PDR 및 대조군 MH 환자로부터 얻은 각각의 샘플 500 μl을 2-DE 및 LC-MS/MS 시험을 위하여 각각 혼합(pooling)하였다.
(3) 비-IS-제거된 PDR 샘플의 2차원 겔 전기영동
혼합된 PDR 유리체 샘플 100 μl 중의 단백질 약 560 μg을 TCA/아세톤 침전시켰다. 5배 용적의 10 mM DTT를 함유하는 아세톤 중의 10% TCA를 유리체 용액에 가하고, -20 ℃에서 4 시간 동안 저장하고, 28,000 g로 10 분 동안 원심분리한 후, 상등액을 제거하였다. 5배 용적의 차갑게 냉각시킨(ice-cold) 아세톤을 상기 침전물에 가하고, 상등액을 제거하여 잔류 TCA를 제거하였다. 얻어진 펠렛을 진공(speed vacuum)을 사용하여 건조한 후, 250 μl 재수화 완충액 [7 M 우레아, 2 M 티오우레아, 2% CHAPS, 60 mM DTT 및 0.5% (v/v) 파말라이트(pharmalyte), (pH 3-10)]에 현탁시켰다. 재수화 용액 중의 펠렛화된 유리체 단백질의 농도는 약 2 μg/μl (약 25%의 계산손실(calculated loss))이었다. 프리-캐스트 고정 pH 구배 스트립(Pre-cast immobilized pH gradient strips) (IPG strips, 13 cm, pH 4-7, linear, Amersham Biosciences, Uppsala, Sweden)를 재수화 완충액을 사용하여 카세트 내에서 밤새(12 hr) 재수화시켰다. IEF 접시 상에서 IPG 스트립을 정렬시킨 후, 전압을 단계적으로(incrementally) 증가시켰다. 처음에는 500 V를 1 시간 동안 가하였고, 이후 1000 V를 1 시간 동안, 최종적으로 8000 V를 14,500 VHr로 가하였다. IPG 스트립을 30 분 동안 환원 용액 (50 mM TrisHCl, pH 8.8, 6 M 우레아, 30% (v/v) 글리세롤, 2% (w/v) 소듐 도데실 설페이트, 1% (w/v) DTT) 중에서 30분 동안, 및 알킬화 용액 (DTT 대신 2.5% (w/v) 아이오도아세트아미드가 치환된 것을 제외하고는 상기 환원 용액과 동일) 중에서 30 분 동안 평형시켰다. 표준 SDS-PAGE 프로토콜 및 SE 600 Ruby gel unit (GE Healthcare, Uppsala, Sweden)를 사용하여 10% 폴리아크릴아미드 겔을 사용하여 SDS-PAGE를 수행하였다. 얻어진 겔을 실버 염색 용액으로 염색하였다. 2-DE 시험을 3회 수행하여 일치되게 검출되는 스팟을 얻었다.
(4) IS-제거된 PDR 샘플의 2 차원 겔 전기영동
12개의 대량 단백질(high abundance proteins)을 면역친화성 제거(immunoaffinity subtraction, IS) 시스템 (Beckman Coulter ProteomeLab IgY-12 column, Beckman Coulter, Fullerton, CA)을 사용하여, 제조자 지침서에 따라 PDR 유리체 샘플로부터 제거하였다. 상기 12개의 단백질은 다음과 같다: 인간 혈청 알부민(human serum albumin), IgG, 피브리노오겐, 트랜스페린(transferrin), IgA, IgM, HDL (apo A-I, apo A-II), 햅토글로빈(haptoglobin), α1-안티트립신(α1-antitrypsin), α1-산 글라이코프로틴(α1-acid glycoprotein), 및 α2-마크로글로불린(α2-macroglobulin). 600 μg의 PDR 유리체 단백질을 IgY-12에 6번(컬럼 수용능력 때문) 로딩하였다. 대량 단백질(high abundance proteins)은 항체 수지에 결합되므로, 통과(flow-through) 분획에서 미량 단백질(low abundance proteins)을 얻고, 제조자 지침서에 따라 스트립핑 완충액을 사용하여 회수하였다. Slide-A-Lyzer 3.5K dialysis cassettes kits (PIERCE, Rockford, IL)를 사용하여, 증류수 2 리터에 대하여 3회 투석함으로써 투과 및 결합 분획 중의 펩타이드를 탈염시켰다. 이후, Amicon Ultra-4 10,000 (MILLIPORE, Bedford, MA)를 사용하고, 5 ml의 재수화 완충액을 사용하여 완충액 교환을 수행하였다. 상기에서 얻어진 두 개의 샘플(미량 및 대량 단백질)을, 상기에서 언급한 바와 같이, 2-DE로 각각 분리 및 시각화하였다. 2-DE 시험을 3회 수행하여 일치되게 검출되는 스팟을 얻었다.
(5) 겔내(In-gel) 트립신 소화
잘라낸 겔 조각들을 30 mM 포타슘 페리시아나이드/100 mM 소듐 티오설페이트중에서 탈-염색시키고, 페리시아나이드의 노란색이 완전히 없어질 때까지 150 μl의 증류수로 수회 린스하였다. 이들이 불투명한 흰색으로 변할 때까지 100% 아세토니트릴로 탈수하고, 100 mM 암모늄 바이카르보네이트로 투명할 때까지 재수화시켰다. 이러한 탈수 및 수화 과정을 3회 반복하고, 100% 아세토니트릴 중에서 단회 탈수시켰다. 상기 겔 조각을 진공 원심분리로 건조시키고, 4 ℃에서 45 분 동안 소화 완충액(50 mM 암모늄 바이카르보네이트 중에 0.01 μg/μl의 농도로 변형된 포크린(porcine) 트립신 함유, (Promega, Madison, WI)) 중에서 재수화시켰다. 과량의 상등액을 제거하고, 겔 조각을 밤새(16 시간) 37 ℃에서 30 μl의 50 mM 암모늄 바이카르보네이트(NH4HCO3) 중에 담갔다. 절단된 펩타이드를 함유하는 상기 용액을 새로운 시험관에 옮겼다.
(6) 2-DE를 위한 팹타이드 매스 핑거프린팅(Peptide mass fingerprinting )
Self-pack poros 20 R2 (Applied Biosystems, Foster City, CA) 수지를 GEloader 팁 (Eppendorf AG, Hamburg, Germany) 내부에 충진하고, 팁의 말단을 꼬아 충진된 수지가 약 2 mm 길이가 되도록 하였다. 트립신-소화된 펩타이드를 상기 수지에 결합시키고 0.1% 트리플루오로아세트산(Trifluoroacetic Acid, TFA)으로 세척하였다. 결합된 펩타이드들을 1 μl의 샘플 매트릭스(70% ACN 및 0.1% TFA 중의 5 mg/ml의 α-시아노-4-히드록시 신남산 용액)으로 용리시켰다. 용리된 펩타이드를 196 웰 MALDI 플레이트에 스팟팅하였다. 4700 프로테오믹스 분석기(4700 proteomics analyzer) (Applied Biosystems, Foster City, CA)을 MS 모드로 사용하여 펩타이드 매스 핑커프린팅(eptide mass fingerprinting, PMF)에 의해 단백질을 동정하였다. 상기 장비는 4700 cal mix (Applied Biosystems, Foster City, CA)를 사용하여 캘리브레이션하였으며, 상기 4700 cal mix는 des-Arg-Bradykinin (monoisotopic mass: 904.4681), 안지오텐신 I (monoisotopic mass: 1296.6853), Glu-Fibrinopeptide B (monoisotopic mass: 1570.6774), ACTH (1-17 clip, monoisotopic mass: 2093.0867), ACTH (18-39 clip, monoisotopic mass: 2465.1989) 및 ACTH (7-38 clip, monoisotopic mass: 3657.9294)을 함유한다. 355 nm 및 200 Hz에서 고정된 강도(intensity) Nd:YAG laser의 3,000 shots를 사용하여 MS 데이터를 얻었다.
(7) 2-DE용 PMF 데이터 분석
GPS explorer software v3.5 및 MASCOT v1.9 (Matrix Science, Boston, MA)을 데이터베이스 검색 엔진으로 사용하여 2-DE로부터 얻은 겔내(in-gel) 소화된 펩타이드 샘플에 대한 PMF 프로테오믹 검색을 수행하였다. 최소 S/N은 10으로 맞추고, 검색 중 다음 오염(contaminant) 피크는 제외시켰다: 842.4, 870.5, 856.5, 771.1, 1794.8, 1475.7, 1993.9, 1383.6, 2211.1, 2705.1, 3338.8, 886.9, 893.0. 절단되지 않은 반응부위는 프로테아제로서 트립신에 대해서는 1로 맞추고, 프리커서 전하는 +1에서 맞추었다. 허용되는 펩타이드 변경(differential peptide modifications)은 시스테인의 카르브아미도메틸화(carbamidomethylation) 및 메티오닌의 산화였다. 얻어진 질량 값을 NCBInr 데이터베이스(updated 20th Feb, 2007) 상에서, 150 ppm의 펩타이드 매스 톨러런스(peptide mass tolerance)를 가지고 검색하였다. 컨피던스 인덱스(Confidence Index, C.I.) >95% 를 갖는 동정된 단백질만을 수용하였다.
(8) LC-MALDI-MS/MS 분석에 의한 나도 LC 분리 및 단백질 동정
11 명의 PDR 환자로부터 얻은 알부민/IgG 제거된 PDR 샘플, 11 명의 동일한 환자로부터 얻은 비-알부민/IgG-제거된 PDR 샘플, 및 14 MH 환자로부터 얻은 대조군 샘플(Table 1)을 풀링하고, SDS-PAGE 겔 (10% 겔) 상에 로딩하였다. 각 샘플 세트(알부민/IgG 제거된 PDR, 비-제거된 PDR 및 비-제거된 대조군)의 1 mg을 두개의 레인에 로딩하였다 (각각 500 μg, Fig. 3A). 상기 알부민/IgG 제거된 PDR 샘플은 SDS-PAGE에 로딩하기 전에 ProteoExtract albumin/IgG removal kit (Calbiochem, San Diego, CA)를 사용하여 PDR 샘플중에서 알부민 및 IgG을 제거하여 준비하였다. 은 염색 후, 겔을 16 조각으로 자르고, 각각의 조각을 상기한 바와 같이 겔내 소화시켰다. 소화된 펩타이드를 진공-건조시키고 물 중의 0.1% TFA 또는 0.1% 포름산 중에서 분해하였다. 이들을 탈염시키고, ZiptipC18 Pipette Tip (Millipore, MA)을 사용하여 농축하였다.
사용된 나노 LC 시스템은 MALDI-TOF/TOF (off-line LC-MALDI-MS/MS)에 오프-라인(off-line) 커플링된 Ultimate 3000 unit (Switchos and Probot, Dionex, Amsterdam)이다. 상기 시스템은 μ-Precolumn Cartridge (300 um i.d. × 5 mm, C18 pepmap100, 5 μm, 100 A, Dionex, Amsterdam) 및 역상 나노 시리스 컬럼reverse phase nano series column (75 μm i.d. × 15 cm long column, C18 PepMap100, 3 μm, 100Å, Dionex)이 장착되어 있다. 초기에, 상기 트립신에 의해 생성된 펩타이드 단편을 20 μl의 0.1% TFA에 용해시키고, 20 μl 샘플 루우프가 장착된 자동주입기(autosampler)를 사용하여 나노 LC 시스템으로 주입하였다. 주입은 10 μl 주입 용량을 사용하여 부분 루우프 모드(partial loop mode)로 수행하였다. 상기 트립신에 의해 생성된 펩타이드 단편은 초기에 프리컬럼(precolumn)에 트랩(trap)되고, 이 후 0.05% TFA로 0.030 ml/min으로 5 분 동안 세척된다. 결합된 펩타이드를 함유하는 상기 프리컬럼은 밸브 스위치를 사용하여 15 cm 나노 컬럼에 연결된다.
펩타이드 단편을 용리시키는 이동상(mobile phase)은 물 중의 0.05% TFA, 5% 아세토니트릴(용액 A) 및 물 중의 0.04% TFA, 80% 아세토니트릴(용액 B)로 구성되었다. 이동상 조성을 용액 B 0에서 50%로 30 분 동안 증기시킴으로써 용액 지수적 구배 용리(Exponential gradient elution)를 수행하였다. 상기 구배를 90% B로 5분 동안 경사지게 하고 0% 용액 B로 20분 동안 거꾸로 경사지게 하여 다음 조작을 위해 상기 컬럼을 평형화시켰다. 총 조작 시간(run time)은 60 분이었다. 상기 구배를 300 nl/min로 실온에서 상기 나노 컬럼에 적용하였다. 용리는 214 nm에서 UV 흡광도로 모니터하였다. 분획화된 펩타이드를 Probot system (Dionex)를 사용하여 스팟 당 20 초로 144 well MALDI plate에 스팟팅하였다. 상기 MALDI plate 상에 스팟팅할 때, 0.976 μl/min 속도로 상기 이동상과 매트릭스 용액(36.0%의 메탄올, 56.0%의 아세토니트릴 및 8.0% 증류수 중의 6.2 mg/ml의α-시아노-4-히드록시 신남산(Agilent Technologies, Santa Clara, CA))을 혼합하였다. 펩타이드 질량 값을 상기 2-DE 분석 및 4700 분석기에 대하여 언급된 파라미터를 사용하여 분석하였다. 10을 초과하는 S/N 비율을 갖는 상기 15개의 가장 강한 펩타이드를 MS/MS에 적용하였다. 충돌 에너지는 1 kV에 맞추었고, 충돌 가스는 공기였다. GPS 익스플로러 소프트웨어(v3.5) 및 MASCOT 검색 엔진(v1.9)을 사용하고, 2-DE PMF 분석을 위해 사용한 동일한 파라미터(피크 필터링 없이)를 사용하여 MS/MS 분석을 수행하였다. Human International Protein Index (IPI) 단백질 서열 데이터베이스에 대하여 검색을 수행하였으며, 알려진 오염물 (IPI versions 3.24, www.ebi.ac.uk/IPI/)에 대한 검색을 포함시켰다. 'dat' 파일 연장(extension)을 갖는 LC-MALDI-MS/MS 분석으로부터 얻어진 MASCOT 검색 결과는 추가의 검증(validation)을 위하여 웹(http://www.proteomecenter.org/)상의 지시서에 따라, Trans-Proteomic Pipeline (TPP)를 사용하여 pepXML 파일로 변환시켰다.
(9) 나노 LC 분리 및 LC-ESI-MS/MS에 의한 단백질 동정
MALDI 이온화 및 MASCOT 알고리즘에 근거한 LC-MALDI-MS/MS 방법과 대조적으로, LC-ESI-MSMS 결과는 ESI 이온화 및 SEQUEST 알고리즘에 근거한다. 따라서, SDS-PAGE 겔로부터 얻은 겔내 소화된 펩타이드 샘플의 다른 반을 나노 LC-ESI-MS/MS를 사용한 단백질 동정에 사용하였다.
공간 전하 제한을 피하기 위한 자동 게인 대조군(automatic gain control)이 장착된 Thermo Electron model LTQ electrospray ionization linear single-quadrupole ion trap mass spectrometer (Thermo Fisher Scientific, Inc. Waltham, MA)에 binary Agilent nanoflow 1200 series HPLC system (Agilent Technologies Inc., Santa Clara, CA)을 직접 커플링시켰다. 10 μl의 수성 포름산 중의 겔내 소화된 펩타이드(0.1%)를 상기 나노 LC-ESI-MS/MS 장비에 주입하였다. 펩타이드를 역상 컬럼 크로마토그래피에 의해 분리시키고, 12 cm × 75 um capillary column packed in-house (Magic C18aq, Michrom Bioresources, Inc., Auburn, CA)에 헬륨 가압 셀을 사용하여 로딩하였다. 90% 용매 A (H2O 중의 포름산 0.1%)에서 40% 용매 B (아세토니트릴 중의 포름산 0.1%)를 사용하여 250 nl/min으로 120 분 동안 프로테옴 샘플의 구배 용리를 수행하였다. 교차 오염을 피하기 위하여 샘플 조작 사이에서 블랭크 조작(blank run)을 수행하였다.
300-2000 m/z로부터 3개 데이터-의존 MS/MS 스캔에 의해 MS 검사 스캐닝을 사용하였다 (분리 범위(isolation width) 2 m/z, 정상화된 충돌 에너지 35%, 다이나믹 익스클루젼 간격(dynamic exclusion duration) 30 초). 텐덤 질량 스펙트럼(tandem mass spectra)으로부터의 단백질 동정은 먼저 SEQUEST 검색 소프트웨어(Sequest cluster v3.2, MS 피크로부터 단백질 동정을 위한 초기 질량 톨러런스는 3 Da 이었고, MS/MS 피크로부터는 1 Da 이었다. 두 개의 잘못된 절단이 허용되었다)를 사용하여 상기한 MASCOT와 동일한 IPI 데이터베이스에 대하여 수행하였다. LC-ESI-MS/MS 분석(LTQ)에 근거한 SEQUEST 검색 결과는 TPP (http://www.proteomecenter.org/)를 사용하여 추가의 검증을 위해 pepXML 파일로 전환시켰다.
(10) Trans-Proteomic Pipeline을 사용한 필터링 검색
pepXML 형식의 MASCOT 및 SEQUEST으로부터 얻은 검색 결과 파일을 주어진 지침서(http://www.proteomecenter.org/)에 따라, TPP 내 PeptideProphet 및 ProteinProphet 모듈을 사용하여 가공하였다. MS/MS 분석에 의해 서열결정된 펩타이드는, 모든 서열결정된 펩타이드들에 대하여 이온 값(ion score), 동정 값(identity score), 상동성 값(homology score), MASCOT 결과의 경우 NTT, 및 SEQUEST 결과에 대한 Xcorr, dCn, Sp, NTT 등의 파라미터에 근거한 가능성(probability)을 할당하도록, PeptideProphet에 의하여 검증하였다. ProteinProphet는 이들 펩타이드들을 검증하였으며, 이들 펩타이드를 가장 포함할 것으로 예상되는 펩타이드들을 결정한다. PeptideProphet 및 ProteinProphet 모듈을 조작하기 위한 가능성 컷-오프는 각각 0.50 및 0.90로 맞추었다. pepXML을 생성하고, PeptideProphet 및 ProteinProphet에 의한 가능성 값(scoring probabilities)을 결정하는 모든 과정은 상기한 MASCOT 및 SEQUEST 데이터베이스에 대하여 수행되었다. ProteinProphet로부터의 최종 TPP 결과는 데이터 결합(merging) 및 비교를 위하여 Excel 파일로 보냈다. TPP에 의한 처리에 의해 단백질 목록 중에서 높은 가능성 및 감소된 과잉성(redundancy)를 갖는 단백질을 구성하는 한정된(definite) 유리체 프로테옴 프로파일을 결정할 수 있다.
(11) 유전자 온톨로지 주석(gene ontology annotation)을 위한 처리
IPI accession numbers는 IPI 데이터베이스에서 매치된 접근 번호를 검색함으로써 Uniprot accession numbers (Swiss-prot numbers 또는 TrEMBL numbers)로 번역하였다. 유전자 온톨로지(gene ontology, GO)는 QuickGO web tool (http://www.ebi.ac.uk/ego/)를 사용하여 Uniprot 번호로 할당되었다. 각각의 Uniprot 번호는 세 개의 카테고리 즉, 생물학적 과정, 기능, 및 성분으로 할당되었다. 상세한 GO 주석으로부터 야기되는 복잡성을 피하기 위하여, GO slim (level 3)을 적용하였다. 단일의 단백질이 몇 가지 과정, 기능, 또는 성분에 의해 주석될 경우, 모든 상기 주석은 데이터 서술(representation)에 여분으로 반영시켰다.
2. 결과 및 고찰
(1) 2차원 겔 전기영동에 의한 PDR 유리체액(vitreous humor)으로부터의 단백질 동정
IgY-12 컬럼은 종래에 인간 또는 영장류의 생물학적 체액으로부터 12개의 대량 단백질(high abudant proteins)을 제거하는데 사용되어 왔다. 유사하게, PDR 유리 샘플들을 IgY-12 컬럼을 사용하여 처리하였으며, 이어서 얻어진 대량 및 소량 단백질 (high and low abudant proteins) 분획을 2-DE에 적용하였다. 47개 스팟을 소량 단백질(low abudant proteins) 겔로부터 얻었으며, 6 개의 스팟이 NCBInr 데이터베이스에 매치되었고(12.8%), 5개의 프로틴이 동정되었다 (도 2 참조). 116개 스팟을 대량 단백질(high abudant proteins) 겔로부터 얻었으며, 87 개가 데이터베이스에 매치되었고(75.0%), 25개의 프로틴이 동정되었다 (도 2 참조). 또한, 본 발명자들은 면역친화성 제거(immunoaffinity subtraction (IS))를 받지 않은 PDR 샘플에 대해서 2-DE를 수행하였다. 총 69개 스팟을 얻었으며, 54 개가 매치되었고 (78.3%), 28개 단백질이 동정되었다 (도 2 참조). 3개 샘플에서 동정된 단백질 목록으로부터 49 개 단백질을 동정하였다 (도 2 참조).
동정율(identification rate)은 소량 단백질(low abudant proteins) 겔에서 낮았다. 상기 47개의 스팟 중, 단지 6개가 NCBInr 데이터베이스에 매치되었다 (12.8%). 이는 겔내(in-gel) 소화 후의 낮은 농도의 스팟들 또는 소량 단백질(low abudant proteins)의 낮은 수율에 기인한 것일 수 있다. 그러므로, MH 유리체액 중의 상기 단백질 농도가 PDR 유리체액 중의 그것에 비해 대략 10분의 1이었기 때문에(MH 단백질 농도는 0.47 μg/μl이었으며, PDR 농도는 4.13 μg/μl이었다), 본 발명자들은 MH 대조군 샘플에서 IS를 수행하지 않았다. 따라서, 더 큰 샘플량이 얻어져야 하며, 더 민감한 기구(장비)가 MH 유리체(MH vitreous)중의 소량 단백질(low abudant proteins)을 동정하기 위해 사용되어야 한다.
소량 (low abudant) PDG 겔 중에서 동정된 5개의 단백질 중, 단지 2개의 단백질(hemopexin and ARL6IP4)만이 소량(low abudant) PDR 겔에서 검출되었으나(도 2) 다른 두 겔들(대량(high abundance) PDR 겔 및 비-IS-처리 PDR 겔)에서는 검출되지 않았다. 어떠한 새로운 단백질도 소량 (low abudant) PDR 프로틴 겔에서 동정되지 않았으나, 소량 (low abudant) PDR 단백질의 2-DE 겔 이미지는 비-IS-처리된 PDR 단백질들의 그것과 달랐으며, 이는 더욱 낮은 그 방법의 검출 한계를 갖는 풍부한(enriched) 분획에서 더욱 소량의(low abudant) 단백질이 동정되었을 가능성을 시사한다.
(2) 나노 LC-MALDI-MS/MS를 사용한 유리 단백질의 동정
PDR 및 대조군 MH 샘플 중의 소량 단백질(low abudant proteins)을 검출하기 위하여, 본 발명자들은 오프-라인(off-line) 나노 LC-MALDI-MS/MS를사용하여 나노 LC 분획화 및 단백질 동정을 수행하였다.
IS-제거된 PDR 샘플 중의 대량 단백질(high abudant proteins)의 2-DE 겔 패턴은 대응되는 비-IS-제거된 PDR 샘플에서의 그것과 유사했으며, 이는 대량 단백질(high abudant proteins)이 유래체액 중의 대부분의 단백질임을 암시한다. 그러므로, 본 발명자들은 제거된 PDR 유리 샘플을 준비하기 위하여 상대적으로 낮은 제거 방법을 사용하기로 결정하였으며, 즉 나노 LC-MALDI-MS/MS를 위한 PDG 샘플을 제거하기 위하여, 본 발명자들은 Calbiochem kit를 사용하여 두 개의 가장 풍부한 단백질, 즉 알부민 및 IgG만을 제거하였다.
제조된 PDR, 알부민/IgG 제거된 PDR, 및 대조군 MH 유리 샘플을 SDS-PAGE 겔에서 올리고, 겔들을 공평하게 16개의 분획으로 잘랐다 (도 3의 A). 겔내(in-gel) 트립신 소화 후, 0.1% TFA 용액 20 μl 중의 단백질을 오토샘플러가 장착된 나노 LC에 20 μl 샘플 루우프를 사용하여 주입하였다. 주입된 펩타이드에 대하여 16 회 나노 LC 분리를 수행하였으며, 각각의 나노 LC 조작은 교차 오염을 회피하기 위하여 블랭크 조작을 이어서 수행하였다. 나노 LC로부터 용리된 펩타이드들을 MALDI 표적 플레이트에 모아 (도 3의 B), MS/MS 모드로 분석하였으며 (도 3의 C 및 D), 검색 결과는 PeptideProphet 및 TPP 중의 ProteinProphet을 사용하여 다시 검증하였였다.
그 결과(도 4의 A), 54개의 단백질이 알부민/IgG 제거된 PDR 샘플에서 동정되었고, 49개가 비-제거된 PDR 샘플에서 동정되었다. 대조군 샘플에서, 50개의 단백질이 동정되었다. 총 83개의 단백질이 이들 세 개의 유리체 샘플에서 동정되었다. 상기 동정된 단백질의 벤다이어그램을 도 4의 A에 제공한다.
본 발명자들은 상기 2-DE 및 LC-MALDI-MS/MS 실험을 위해 NCBInr 데이터베이스 (updated 20th Feb, 2007) 및 IPI 데이터베이스 (v3.24)를 사용하여 데이터베이스 검색을 수행하였다. NCBInr 데이터베이스로부터 얻어진 결과는 포함되지 않았다 (데이터 미개시), 이는 데이터를 장황하고 복잡하게 하는 것을 방지하기 위함이다. 결과적으로, 본 발명자들은 실험적 효율성의 이유로 IPI 데이터베이스만을 사용했다.
(3) 나노 LC-ESI-MS/MS를 사용한 유리체 단백질의 동정
단백질 동정을 증가시키기 위하여, 본 발명자들은 보조 분석 플랫폼 즉, 나노 LC-ESI-MS/MS를 사용했다. 나노 LC-ESI-MS/MS 시험 결과(도 4의 B), 356개 단백질이 알부민/IgG 제거된 PDR 유리체액에서 동정되었으며, 136개 단백질이 비-제거된 PDR 유리체액에서 동정되었고, 335개 단백질이 대조군 MH 유리체 샘플에서 동정되었다. 총 518개 단백질이, LC-ESI-MS/MS를 사용하여, 비-제거된 PDR, 알부민/IgG 제거된 PDR, 및 대조군 MH 유리체 샘플에서 동정되었다 (도 4의 B). 518개 단백질 중 183개 단백질(벤다이어그램의 A, B, C)은 PDR 유리체에서만 존재하는 것으로 밝혀졌고, 115개 단백질(벤다이어그램의 G)은 대조군 유리체에서만 존재하는 것으로 밝혀졌다. 220개 단백질은 벤다이어그램의 중첩된 부위에 존재한다 (벤다이어그램의 D, E, F).
(4) LC-MALDI-MS/MS 및 LC-ESI-MS/MS로부터 동정된 단백질의 목록
이들 두 개의 상이한 이온화 방법(MALDI 및 ESI)을 사용하여 동정된 단백질을 합하여 집합적 유리체 프로테옴을 생성하였다. LC-MALDI-MS/MS에 의해 동정된 83개 단백질 및 LC-ESI-MS/MS에 의해 동정된 518개 단백질은 531개 단백질로 이루어진 합쳐진 유리체 프로테옴 프로파일을 생성하였다 (도 4의 C). 이들 두 개의 LC-MS/MS 실험으로부터 동정된 단백질 목록은 2-DE에 의해 동정된 모든 단백질들을 포함한다.
유리체액의 단백질체 프로파일은 혈청의 그것과 유사한 것을 제안되어 왔다 [24]. 그러나, 몇몇의 단백질은 유리체 샘플에 존재하는 것으로 보고된 바 있으며, 예를 들어, pigment epithelium-derived factor (PEDF), prostaglandin-D2 synthase, plasma glutathione peroxidase, 및 interphotoreceptor retinoid-binding protein (IRBP) [24] 들이며, 이들은 또한 본 연구에서도 검출되었다.
또한, 유리체에서 기존에 보고된 바 없는, 240개의 유리체 단백질들이 동정되었으며, 이들은 hepatocyte growth factor activator, kallistatin, thioredoxin, von Willebrand factor (vWF), Wnt inhibitory factor, chromogranin 및 secreted frizzled-related protein을 포함한다 (도 6a 내지 도 6g 참조). 또한, 이들 동정된 단백질들 중 몇몇은 인간의 혈장 프로테옴에서도 검출된 바 있다 (도 6a 내지 도 6g 참조). 동정된 상기 531개 유리체 단백질을, 9,504 혈장 단백질을 목록화한, HUPO PPP 협회 (Human Proteome Organization, Plasma Proteome Project)에 의해 생성된 혈장 프로테옴과 비교하였다 (http://www.bioinformatics.med.umich.edu/hupo/ppp). 상기 유리체 프로테옴 내의 531개 단백질 중, 304개는 혈장 중에서 발견된 바 없으며, 240개의 새롭게 검출된 유리체 단백질 중 132개는 혈장에서 발견된 바 없다.
특히, 벤다이어그램 중 위치 A, B, C 및 G (도 4의 C)는 PDR 또는 대조군에서만 검출되었던 단백질을 나타낸다. 185개 단백질이 PDR (도 4의 C의 A, B, 및 C)에서만 검출된 반면, 116개 단백질이 대조군(도 4의 C의 G)에서만 검출되었다.
(5) 유전자 온톨로지(Gene ontology, GO) 주석을 통한 유리체 단백질의 특성분석(Characterization)
도 6a 내지 도 6g의 동정된 단백질을 상위 수준의 유전자 온톨로지 (GO slim, level 3) (http://www.ebi.ac.uk/ego/)를 사용하여 주석하였다. GO 주석에 근거하여, 제거된 PDR, 비-제거된 PDR, 및 대조군 MH 샘플 중의 각각의 동정된 단백질에 대하여, 본 발명자들은 "생물학적 과정", "분자 기능", 및 "세포 성분"을 할당할 수 있었다. "분자 기능" 및 "세포 성분" 카테고리를 위하여, 동정된 단백질 대부분을 각각 "결합" 및 "세포외 부위"의 서브카테고리로 주로 선택했다 (데이터 미기재)
"생물학적 과정"의 카테고리 중 "면역 시스템 과정" 및 "자극에 대한 반응" 서브카테고리로 할당된 단백질의 수가 대조군 또는 제거된 PDR에서 보다 비-제거된 PDR에서 더 높았다(도 5)는 것 이외에, 놀랍게도, GO 주석의 패턴 관점에서, PDR 및 대조군 유리체 단백질 사이에서 유의성 있는 차이가 발견되지 않았다. 이는 다른 두 개의 샘플 세트보다 비-제거된 PDR이 더 많은 면역글로불린 및 보체 성분 종을 포함하는 것을 나타낼 수 있으며, 이는 "면역 시스템 과정" 및 "자극에 대한 반응"이 상기 두 개의 서브카테고리에 관련된 더욱 많은 단백질 생성물들을 함유하고 있기 때문이다. 선택적으로, 이들 두 개의 서브카테고리의 증가는 또한 PDR에서 증가된 혈관 투과성 또는 혈액-망막 장벽의 파괴의 결과인 것으로 또한 생각될 수 있다. 한편으로, 이러한 증가는 또한 제거된 PDR 샘플로부터 알부민 및 IgG가 실질적으로 제거되었다는 사실로부터 유추될 수 있다.
결론적으로, 상기 GO 주석 연구는 유리체에는 다양한 종류의 단백질이 존재하며, 이들은 망막 질병에 있어서의 생리학적 및 병리학적 변화 및 병리 증상에서 유리체 망막 상호작용을 반영할 수 있음을 나타낸다. PDR 및 MH 유리체 샘플에서의 단백질 농도가 10 배 상이할지라도, 두 샘플 중의 단백질 프로파일은 유사하며, 이는 GO 주석 프로파일 카테고리 "생물학적 과정"으로부터 알 수 있다 (도 5). 새로운 별개의 병인성 단백질이 생성되기 보다는 비-당뇨병성 유리체 단백질의 10 배 수준으로 단백질을 증가시키는 정도로, 대부분의 존재하는 유리체 단백질의 농도가 PDR 진행과 함께 증가하는 것을 생각할 수 있다.
3. 결론
상기 시험에서, 531 단백질이 유리체 프로테옴에서 동정되었으며, 415개 및 346개 단백질이 각각 PDR 및 대조군 MH 유리체 샘플에서 동정되었다. 동정된 531개 단백질 중, 240개 단백질이 본 시험에서 최초로 동정되었다. 또한, 새롭게 검출된 240개 단백질 중 132 단백질을 포함한, 상기 531 단백질 중 304개 단백질은 HUPO 혈장 프로테옴(http://www.bioinformatics.med.umich.edu/hupo/ppp)에 기재되어 있지 않다. 상기 단백질 목록은 또한 PDR 및 정상 유리체 샘플에 대한 가장 이해될 수 있는 프로테옴이며, 당뇨병성 망막병증과 같은 유리체망막 질환을 연구하는 자들을 위해 기초적인 정보를 제공한다.
도 1은 2-DE/MALDI-MS, LC-MALDI-MS/MS, 및 LC-ESI-MS/MS 시험의 개요를 나타낸다.
도 2는 2-DE에 의해 동정된 PDR 단백질의 벤다이어그램을 나타낸다.
도 3은 SDS-PAGE 및 LC-MALDI-MS/MS에 의해 단밸질을 동정하는데 사용된 과정을 나타낸다.
도 4는 LC-MALDI-MS/MS 및 LC-ESI-MS/MS에 의해 동정된 단백질의 벤다이어그램을 나타낸다.
도 5는 3 개의 유리체 샘플에 대한 GO 주석인 "생물학적 과정"의 서브카테고리를 나타낸다.
도 6a 내지 도 6g은 알부민/IgG 제거된 PDR 샘플, 비-알부민/IgG 제거된 PDR 샘플, 및 대조군 MH 유리체 샘플에 대한 LC-MS/MS 분석으로부터 얻어진 총 단백질 목록을 나타낸다.
<110> Seoul National University Industry Foundation <120> Biomarker composition for detecting diabetic retinopathy and diagnostic kit therefor <130> PN0136 <160> 105 <170> KopatentIn 1.71 <210> 1 <211> 914 <212> PRT <213> Homo sapiens <400> 1 Met Lys Pro Pro Arg Pro Val Arg Thr Cys Ser Lys Val Leu Val Leu 1 5 10 15 Leu Ser Leu Leu Ala Ile His Gln Thr Thr Thr Ala Glu Lys Asn Gly 20 25 30 Ile Asp Ile Tyr Ser Leu Thr Val Asp Ser Arg Val Ser Ser Arg Phe 35 40 45 Ala His Thr Val Val Thr Ser Arg Val Val Asn Arg Ala Asn Thr Val 50 55 60 Gln Glu Ala Thr Phe Gln Met Glu Leu Pro Lys Lys Ala Phe Ile Thr 65 70 75 80 Asn Phe Ser Met Ile Ile Asp Gly Met Thr Tyr Pro Gly Ile Ile Lys 85 90 95 Glu Lys Ala Glu Ala Gln Ala Gln Tyr Ser Ala Ala Val Ala Lys Gly 100 105 110 Lys Ser Ala Gly Leu Val Lys Ala Thr Gly Arg Asn Met Glu Gln Phe 115 120 125 Gln Val Ser Val Ser Val Ala Pro Asn Ala Lys Ile Thr Phe Glu Leu 130 135 140 Val Tyr Glu Glu Leu Leu Lys Arg Arg Leu Gly Val Tyr Glu Leu Leu 145 150 155 160 Leu Lys Val Arg Pro Gln Gln Leu Val Lys His Leu Gln Met Asp Ile 165 170 175 His Ile Phe Glu Pro Gln Gly Ile Ser Phe Leu Glu Thr Glu Ser Thr 180 185 190 Phe Met Thr Asn Gln Leu Val Asp Ala Leu Thr Thr Trp Gln Asn Lys 195 200 205 Thr Lys Ala His Ile Arg Phe Lys Pro Thr Leu Ser Gln Gln Gln Lys 210 215 220 Ser Pro Glu Gln Gln Glu Thr Val Leu Asp Gly Asn Leu Ile Ile Arg 225 230 235 240 Tyr Asp Val Asp Arg Ala Ile Ser Gly Gly Ser Ile Gln Ile Glu Asn 245 250 255 Gly Tyr Phe Val His Tyr Phe Ala Pro Glu Gly Leu Thr Thr Met Pro 260 265 270 Lys Asn Val Val Phe Val Ile Asp Lys Ser Gly Ser Met Ser Gly Arg 275 280 285 Lys Ile Gln Gln Thr Arg Glu Ala Leu Ile Lys Ile Leu Asp Asp Leu 290 295 300 Ser Pro Arg Asp Gln Phe Asn Leu Ile Val Phe Ser Thr Glu Ala Thr 305 310 315 320 Gln Trp Arg Pro Ser Leu Val Pro Ala Ser Ala Glu Asn Val Asn Lys 325 330 335 Ala Arg Ser Phe Ala Ala Gly Ile Gln Ala Leu Gly Gly Thr Asn Ile 340 345 350 Asn Asp Ala Met Leu Met Ala Val Gln Leu Leu Asp Ser Ser Asn Gln 355 360 365 Glu Glu Arg Leu Pro Glu Gly Ser Val Ser Leu Ile Ile Leu Leu Thr 370 375 380 Asp Gly Asp Pro Thr Val Gly Glu Thr Asn Pro Arg Ser Ile Gln Asn 385 390 395 400 Asn Val Arg Glu Ala Val Ser Gly Arg Tyr Ser Leu Phe Cys Leu Gly 405 410 415 Phe Gly Phe Asp Val Ser Tyr Ala Phe Leu Glu Lys Leu Ala Leu Asp 420 425 430 Asn Gly Gly Leu Ala Arg Arg Ile His Glu Asp Ser Asp Ser Ala Leu 435 440 445 Gln Leu Gln Asp Phe Tyr Gln Glu Val Ala Asn Pro Leu Leu Thr Ala 450 455 460 Val Thr Phe Glu Tyr Pro Ser Asn Ala Val Glu Glu Val Thr Gln Asn 465 470 475 480 Asn Phe Arg Leu Leu Phe Lys Gly Ser Glu Met Val Val Ala Gly Lys 485 490 495 Leu Gln Asp Arg Gly Pro Asp Val Leu Thr Ala Thr Val Ser Gly Lys 500 505 510 Leu Pro Thr Gln Asn Ile Thr Phe Gln Thr Glu Ser Ser Val Ala Glu 515 520 525 Gln Glu Ala Glu Phe Gln Ser Pro Lys Tyr Ile Phe His Asn Phe Met 530 535 540 Glu Arg Leu Trp Ala Tyr Leu Thr Ile Gln Gln Leu Leu Glu Gln Thr 545 550 555 560 Val Ser Ala Ser Asp Ala Asp Gln Gln Ala Leu Arg Asn Gln Ala Leu 565 570 575 Asn Leu Ser Leu Ala Tyr Ser Phe Val Thr Pro Leu Thr Ser Met Val 580 585 590 Val Thr Lys Pro Asp Asp Gln Glu Gln Ser Gln Val Ala Glu Lys Pro 595 600 605 Met Glu Gly Glu Ser Arg Asn Arg Asn Val His Ser Ala Gly Ala Ala 610 615 620 Gly Ser Arg Met Asn Phe Arg Pro Gly Val Leu Ser Ser Arg Gln Leu 625 630 635 640 Gly Leu Pro Gly Pro Pro Asp Val Pro Asp His Ala Ala Tyr His Pro 645 650 655 Phe Arg Arg Leu Ala Ile Leu Pro Ala Ser Ala Pro Pro Ala Thr Ser 660 665 670 Asn Pro Asp Pro Ala Val Ser Arg Val Met Asn Met Lys Ile Glu Glu 675 680 685 Thr Thr Met Thr Thr Gln Thr Pro Ala Cys Pro Ser Cys Ser Arg Ser 690 695 700 Arg Ala Pro Ala Val Pro Ala Pro Ile Gln Ala Pro Ser Ala Ile Leu 705 710 715 720 Pro Leu Pro Gly Gln Ser Val Glu Arg Leu Cys Val Asp Pro Arg His 725 730 735 Arg Gln Gly Pro Val Asn Leu Leu Ser Asp Pro Glu Gln Gly Val Glu 740 745 750 Val Thr Gly Gln Tyr Glu Arg Glu Lys Ala Gly Phe Ser Trp Ile Glu 755 760 765 Val Thr Phe Lys Asn Pro Leu Val Trp Val His Ala Ser Pro Glu His 770 775 780 Val Val Val Thr Arg Asn Arg Arg Ser Ser Ala Tyr Lys Trp Lys Glu 785 790 795 800 Thr Leu Phe Ser Val Met Pro Gly Leu Lys Met Thr Met Asp Lys Thr 805 810 815 Gly Leu Leu Leu Leu Ser Asp Pro Asp Lys Val Thr Ile Gly Leu Leu 820 825 830 Phe Trp Asp Gly Arg Gly Glu Gly Leu Arg Leu Leu Leu Arg Asp Thr 835 840 845 Asp Arg Phe Ser Ser His Val Gly Gly Thr Leu Gly Gln Phe Tyr Gln 850 855 860 Glu Val Leu Trp Gly Ser Pro Ala Ala Ser Asp Asp Gly Arg Arg Thr 865 870 875 880 Leu Arg Val Gln Gly Asn Asp His Ser Ala Thr Arg Glu Arg Arg Leu 885 890 895 Asp Tyr Gln Glu Gly Pro Pro Gly Val Glu Ile Ser Cys Trp Ser Val 900 905 910 Glu Leu <210> 2 <211> 57 <212> PRT <213> Homo sapiens <400> 2 Lys Pro Gly Lys Val Pro Lys His Leu Ile Tyr Ala Ala Ser Ser Leu 1 5 10 15 Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu 20 25 30 Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr 35 40 45 Tyr Cys Leu Gln His Asn Ser Tyr Pro 50 55 <210> 3 <211> 255 <212> PRT <213> Homo sapiens <400> 3 Met Asp Asp Arg Glu Asp Leu Val Tyr Gln Ala Lys Leu Ala Glu Gln 1 5 10 15 Ala Glu Arg Tyr Asp Glu Met Val Glu Ser Met Lys Lys Val Ala Gly 20 25 30 Met Asp Val Glu Leu Thr Val Glu Glu Arg Asn Leu Leu Ser Val Ala 35 40 45 Tyr Lys Asn Val Ile Gly Ala Arg Arg Ala Ser Trp Arg Ile Ile Ser 50 55 60 Ser Ile Glu Gln Lys Glu Glu Asn Lys Gly Gly Glu Asp Lys Leu Lys 65 70 75 80 Met Ile Arg Glu Tyr Arg Gln Met Val Glu Thr Glu Leu Lys Leu Ile 85 90 95 Cys Cys Asp Ile Leu Asp Val Leu Asp Lys His Leu Ile Pro Ala Ala 100 105 110 Asn Thr Gly Glu Ser Lys Val Phe Tyr Tyr Lys Met Lys Gly Asp Tyr 115 120 125 His Arg Tyr Leu Ala Glu Phe Ala Thr Gly Asn Asp Arg Lys Glu Ala 130 135 140 Ala Glu Asn Ser Leu Val Ala Tyr Lys Ala Ala Ser Asp Ile Ala Met 145 150 155 160 Thr Glu Leu Pro Pro Thr His Pro Ile Arg Leu Gly Leu Ala Leu Asn 165 170 175 Phe Ser Val Phe Tyr Tyr Glu Ile Leu Asn Ser Pro Asp Arg Ala Cys 180 185 190 Arg Leu Ala Lys Ala Ala Phe Asp Asp Ala Ile Ala Glu Leu Asp Thr 195 200 205 Leu Ser Glu Glu Ser Tyr Lys Asp Ser Thr Leu Ile Met Gln Leu Leu 210 215 220 Arg Asp Asn Leu Thr Leu Trp Thr Ser Asp Met Gln Gly Asp Gly Glu 225 230 235 240 Glu Gln Asn Lys Glu Ala Leu Gln Asp Val Glu Asp Glu Asn Gln 245 250 255 <210> 4 <211> 156 <212> PRT <213> Homo sapiens <400> 4 Met Ala Thr Lys Ala Val Cys Val Leu Lys Gly Asp Gly Pro Val Gln 1 5 10 15 Gly Ile Ile Asn Phe Glu Gln Lys Ala Arg Ala Gly Thr Glu Ala Leu 20 25 30 Lys Val Trp Gly Ser Ile Lys Gly Leu Thr Glu Gly Leu His Gly Phe 35 40 45 His Val His Glu Phe Gly Asp Asn Thr Ala Gly Cys Thr Ser Ala Gly 50 55 60 Pro His Phe Asn Pro Leu Ser Arg Lys His Gly Gly Pro Lys Asp Glu 65 70 75 80 Glu Arg His Val Gly Asp Leu Gly Asn Val Thr Ala Asp Lys Asp Gly 85 90 95 Val Ala Asp Val Ser Ile Glu Asp Ser Val Ile Ser Leu Ser Gly Asp 100 105 110 His Cys Ile Ile Gly Arg Thr Leu Val Val His Glu Lys Ala Asp Asp 115 120 125 Leu Gly Lys Gly Gly Asn Glu Glu Ser Thr Lys Thr Gly Asn Ala Gly 130 135 140 Ser Arg Leu Ala Cys Gly Val Ile Gly Ile Ala Gln 145 150 155 <210> 5 <211> 1839 <212> PRT <213> Homo sapiens <400> 5 Met Asp Val His Thr Arg Trp Lys Ala Arg Ser Ala Leu Arg Pro Gly 1 5 10 15 Ala Pro Leu Leu Pro Pro Leu Leu Leu Leu Leu Leu Trp Ala Pro Pro 20 25 30 Pro Ser Arg Ala Ala Gln Pro Ala Asp Leu Leu Lys Val Leu Asp Phe 35 40 45 His Asn Leu Pro Asp Gly Ile Thr Lys Thr Thr Gly Phe Cys Ala Thr 50 55 60 Arg Arg Ser Ser Lys Gly Pro Asp Val Ala Tyr Arg Val Thr Lys Asp 65 70 75 80 Ala Gln Leu Ser Ala Pro Thr Lys Gln Leu Tyr Pro Ala Ser Ala Phe 85 90 95 Pro Glu Asp Phe Ser Ile Leu Thr Thr Val Lys Ala Lys Lys Gly Ser 100 105 110 Gln Ala Phe Leu Val Ser Ile Tyr Asn Glu Gln Gly Ile Gln Gln Ile 115 120 125 Gly Leu Glu Leu Gly Arg Ser Pro Val Phe Leu Tyr Glu Asp His Thr 130 135 140 Gly Lys Pro Gly Pro Glu Asp Tyr Pro Leu Phe Arg Gly Ile Asn Leu 145 150 155 160 Ser Asp Gly Lys Trp His Arg Ile Ala Leu Ser Val His Lys Lys Asn 165 170 175 Val Thr Leu Ile Leu Asp Cys Lys Lys Lys Thr Thr Lys Phe Leu Asp 180 185 190 Arg Ser Asp His Pro Met Ile Asp Ile Asn Gly Ile Ile Val Phe Gly 195 200 205 Thr Arg Ile Leu Asp Glu Glu Val Phe Glu Gly Asp Ile Gln Gln Leu 210 215 220 Leu Phe Val Ser Asp His Arg Ala Ala Tyr Asp Tyr Cys Glu His Tyr 225 230 235 240 Ser Pro Asp Cys Asp Thr Ala Val Pro Asp Thr Pro Gln Ser Gln Asp 245 250 255 Pro Asn Pro Asp Glu Tyr Tyr Thr Glu Gly Asp Gly Glu Gly Glu Thr 260 265 270 Tyr Tyr Tyr Glu Tyr Pro Tyr Tyr Glu Asp Pro Glu Asp Leu Gly Lys 275 280 285 Glu Pro Thr Pro Ser Lys Lys Pro Val Glu Ala Ala Lys Glu Thr Thr 290 295 300 Glu Val Pro Glu Glu Leu Thr Pro Thr Pro Thr Glu Ala Ala Pro Met 305 310 315 320 Pro Glu Thr Ser Glu Gly Ala Gly Lys Glu Glu Asp Val Gly Ile Gly 325 330 335 Asp Tyr Asp Tyr Val Pro Ser Glu Asp Tyr Tyr Thr Pro Ser Pro Tyr 340 345 350 Asp Asp Leu Thr Tyr Gly Glu Gly Glu Glu Asn Pro Asp Gln Pro Thr 355 360 365 Asp Pro Gly Ala Gly Ala Glu Ile Pro Thr Ser Thr Ala Asp Thr Ser 370 375 380 Asn Ser Ser Asn Pro Ala Pro Pro Pro Gly Glu Gly Ala Asp Asp Leu 385 390 395 400 Glu Gly Glu Phe Thr Glu Glu Thr Ile Arg Asn Leu Asp Glu Asn Tyr 405 410 415 Tyr Asp Pro Tyr Tyr Asp Pro Thr Ser Ser Pro Ser Glu Ile Gly Pro 420 425 430 Gly Met Pro Ala Asn Gln Asp Thr Ile Tyr Glu Gly Ile Gly Gly Pro 435 440 445 Arg Gly Glu Lys Gly Gln Lys Gly Glu Pro Ala Ile Ile Glu Pro Gly 450 455 460 Met Leu Ile Glu Gly Pro Pro Gly Pro Glu Gly Pro Ala Gly Leu Pro 465 470 475 480 Gly Pro Pro Gly Thr Met Gly Pro Thr Gly Gln Val Gly Asp Pro Gly 485 490 495 Glu Arg Gly Pro Pro Gly Arg Pro Gly Leu Pro Gly Ala Asp Gly Leu 500 505 510 Pro Gly Pro Pro Gly Thr Met Leu Met Leu Pro Phe Arg Phe Gly Gly 515 520 525 Gly Gly Asp Ala Gly Ser Lys Gly Pro Met Val Ser Ala Gln Glu Ser 530 535 540 Gln Ala Gln Ala Ile Leu Gln Gln Ala Arg Leu Ala Leu Arg Gly Pro 545 550 555 560 Ala Gly Pro Met Gly Leu Thr Gly Arg Pro Gly Pro Val Gly Pro Pro 565 570 575 Gly Ser Gly Gly Leu Lys Gly Glu Pro Gly Asp Val Gly Pro Gln Gly 580 585 590 Pro Arg Gly Val Gln Gly Pro Pro Gly Pro Ala Gly Lys Pro Gly Arg 595 600 605 Arg Gly Arg Ala Gly Ser Asp Gly Ala Arg Gly Met Pro Gly Gln Thr 610 615 620 Gly Pro Lys Gly Asp Arg Gly Phe Asp Gly Leu Ala Gly Leu Pro Gly 625 630 635 640 Glu Lys Gly His Arg Gly Asp Pro Gly Pro Ser Gly Pro Pro Gly Pro 645 650 655 Pro Gly Asp Asp Gly Glu Arg Gly Asp Asp Gly Glu Val Gly Pro Arg 660 665 670 Gly Leu Pro Gly Glu Pro Gly Pro Arg Gly Leu Leu Gly Pro Lys Gly 675 680 685 Pro Pro Gly Pro Pro Gly Pro Pro Gly Val Thr Gly Met Asp Gly Gln 690 695 700 Pro Gly Pro Lys Gly Asn Val Gly Pro Gln Gly Glu Pro Gly Pro Pro 705 710 715 720 Gly Gln Gln Gly Asn Pro Gly Ala Gln Gly Leu Pro Gly Pro Gln Gly 725 730 735 Ala Ile Gly Pro Pro Gly Glu Lys Gly Pro Leu Gly Lys Pro Gly Leu 740 745 750 Pro Gly Met Pro Gly Ala Asp Gly Pro Pro Gly His Pro Gly Lys Glu 755 760 765 Gly Pro Pro Gly Glu Lys Gly Gly Gln Gly Pro Pro Gly Pro Gln Gly 770 775 780 Pro Ile Gly Tyr Pro Gly Pro Arg Gly Val Lys Arg Gly Gly Pro Gly 785 790 795 800 Ala Glu Ser Gly Lys Gly Pro Pro Gly Arg Arg Gly Glu Asp Gly Phe 805 810 815 Pro Gly Phe Lys Gly Asp Met Gly Ile Lys Gly Asp Arg Gly Glu Ile 820 825 830 Gly Pro Pro Gly Pro Arg Gly Glu Asp Gly Pro Glu Gly Pro Lys Gly 835 840 845 Arg Gly Gly Pro Asn Gly Asp Pro Gly Pro Leu Gly Pro Pro Gly Glu 850 855 860 Lys Gly Lys Leu Gly Val Pro Gly Leu Pro Gly Tyr Pro Gly Arg Gln 865 870 875 880 Gly Pro Lys Gly Ser Ile Gly Phe Pro Gly Phe Pro Gly Ala Asn Gly 885 890 895 Glu Lys Gly Gly Arg Gly Thr Pro Gly Lys Pro Gly Pro Arg Gly Gln 900 905 910 Arg Gly Pro Thr Gly Pro Arg Gly Glu Arg Gly Pro Arg Gly Ile Thr 915 920 925 Gly Lys Pro Gly Pro Lys Gly Asn Ser Gly Gly Asp Gly Pro Ala Gly 930 935 940 Pro Pro Gly Glu Arg Gly Pro Asn Gly Pro Gln Gly Pro Thr Gly Phe 945 950 955 960 Pro Gly Pro Lys Gly Pro Pro Gly Pro Pro Gly Lys Asp Gly Leu Pro 965 970 975 Gly His Pro Gly Gln Arg Gly Glu Thr Gly Phe Gln Gly Lys Thr Gly 980 985 990 Pro Pro Gly Pro Pro Gly Val Val Gly Pro Gln Gly Pro Thr Gly Glu 995 1000 1005 Thr Gly Pro Met Gly Glu Arg Gly His Pro Gly Pro Pro Gly Pro Pro 1010 1015 1020 Gly Glu Gln Gly Leu Pro Gly Leu Ala Gly Lys Glu Gly Thr Lys Gly 1025 1030 1035 1040 Asp Pro Gly Pro Ala Gly Leu Pro Gly Lys Asp Gly Pro Pro Gly Leu 1045 1050 1055 Arg Gly Phe Pro Gly Asp Arg Gly Leu Pro Gly Pro Val Gly Ala Leu 1060 1065 1070 Gly Leu Lys Gly Asn Glu Gly Pro Pro Gly Pro Pro Gly Pro Ala Gly 1075 1080 1085 Ser Pro Gly Glu Arg Gly Pro Ala Gly Ala Ala Gly Pro Ile Gly Ile 1090 1095 1100 Pro Gly Arg Pro Gly Pro Gln Gly Pro Pro Gly Pro Ala Gly Glu Lys 1105 1110 1115 1120 Gly Ala Pro Gly Glu Lys Gly Pro Gln Gly Pro Ala Gly Arg Asp Gly 1125 1130 1135 Leu Gln Gly Pro Val Gly Leu Pro Gly Pro Ala Gly Pro Val Gly Pro 1140 1145 1150 Pro Gly Glu Asp Gly Asp Lys Gly Glu Ile Gly Glu Pro Gly Gln Lys 1155 1160 1165 Gly Ser Lys Gly Asp Lys Gly Glu Gln Gly Pro Pro Gly Pro Thr Gly 1170 1175 1180 Pro Gln Gly Pro Ile Gly Gln Pro Gly Pro Ser Gly Ala Asp Gly Glu 1185 1190 1195 1200 Pro Gly Pro Arg Gly Gln Gln Gly Leu Phe Gly Gln Lys Gly Asp Glu 1205 1210 1215 Gly Pro Arg Gly Phe Pro Gly Pro Pro Gly Pro Val Gly Leu Gln Gly 1220 1225 1230 Leu Pro Gly Pro Pro Gly Glu Lys Gly Glu Thr Gly Asp Val Gly Gln 1235 1240 1245 Met Gly Pro Pro Gly Pro Pro Gly Pro Arg Gly Pro Ser Gly Ala Pro 1250 1255 1260 Gly Ala Asp Gly Pro Gln Gly Pro Pro Gly Gly Ile Gly Asn Pro Gly 1265 1270 1275 1280 Ala Val Gly Glu Lys Gly Glu Pro Gly Glu Ala Gly Glu Pro Gly Leu 1285 1290 1295 Pro Gly Glu Gly Gly Pro Pro Gly Pro Lys Gly Glu Arg Gly Glu Lys 1300 1305 1310 Gly Glu Ser Gly Pro Ser Gly Ala Ala Gly Pro Pro Gly Pro Lys Gly 1315 1320 1325 Pro Pro Gly Asp Asp Gly Pro Lys Gly Ser Pro Gly Pro Val Gly Phe 1330 1335 1340 Pro Gly Asp Pro Gly Pro Pro Gly Glu Pro Gly Pro Ala Gly Gln Asp 1345 1350 1355 1360 Gly Pro Pro Gly Asp Lys Gly Asp Asp Gly Glu Pro Gly Gln Thr Gly 1365 1370 1375 Ser Pro Gly Pro Thr Gly Glu Pro Gly Pro Ser Gly Pro Pro Gly Lys 1380 1385 1390 Arg Gly Pro Pro Gly Pro Ala Gly Pro Glu Gly Arg Gln Gly Glu Lys 1395 1400 1405 Gly Ala Lys Gly Glu Ala Gly Leu Glu Gly Pro Pro Gly Lys Thr Gly 1410 1415 1420 Pro Ile Gly Pro Gln Gly Ala Pro Gly Lys Pro Gly Pro Asp Gly Leu 1425 1430 1435 1440 Arg Gly Ile Pro Gly Pro Val Gly Glu Gln Gly Leu Pro Gly Ser Pro 1445 1450 1455 Gly Pro Asp Gly Pro Pro Gly Pro Met Gly Pro Pro Gly Leu Pro Gly 1460 1465 1470 Leu Lys Gly Asp Ser Gly Pro Lys Gly Glu Lys Gly His Pro Gly Leu 1475 1480 1485 Ile Gly Leu Ile Gly Pro Pro Gly Glu Gln Gly Glu Lys Gly Asp Arg 1490 1495 1500 Gly Leu Pro Gly Pro Gln Gly Ser Ser Gly Pro Lys Gly Glu Gln Gly 1505 1510 1515 1520 Ile Thr Gly Pro Ser Gly Pro Ile Gly Pro Pro Gly Pro Pro Gly Leu 1525 1530 1535 Pro Gly Pro Pro Gly Pro Lys Gly Ala Lys Gly Ser Ser Gly Pro Thr 1540 1545 1550 Gly Pro Lys Gly Glu Ala Gly His Pro Gly Pro Pro Gly Pro Pro Gly 1555 1560 1565 Pro Pro Gly Glu Val Ile Gln Pro Leu Pro Ile Gln Ala Ser Arg Thr 1570 1575 1580 Arg Arg Asn Ile Asp Ala Ser Gln Leu Leu Asp Asp Gly Asn Gly Glu 1585 1590 1595 1600 Asn Tyr Val Asp Tyr Ala Asp Gly Met Glu Glu Ile Phe Gly Ser Leu 1605 1610 1615 Asn Ser Leu Lys Leu Glu Ile Glu Gln Met Lys Arg Pro Leu Gly Thr 1620 1625 1630 Gln Gln Asn Pro Ala Arg Thr Cys Lys Asp Leu Gln Leu Cys His Pro 1635 1640 1645 Asp Phe Pro Asp Gly Glu Tyr Trp Val Asp Pro Asn Gln Gly Cys Ser 1650 1655 1660 Arg Asp Ser Phe Lys Val Tyr Cys Asn Phe Thr Ala Gly Gly Ser Thr 1665 1670 1675 1680 Cys Val Phe Pro Asp Lys Lys Ser Glu Gly Ala Arg Ile Thr Ser Trp 1685 1690 1695 Pro Lys Glu Asn Pro Gly Ser Trp Phe Ser Glu Phe Lys Arg Gly Lys 1700 1705 1710 Leu Leu Ser Tyr Val Asp Ala Glu Gly Asn Pro Val Gly Val Val Gln 1715 1720 1725 Met Thr Phe Leu Arg Leu Leu Ser Ala Ser Ala His Gln Asn Val Thr 1730 1735 1740 Tyr His Cys Tyr Gln Ser Val Ala Trp Gln Asp Ala Ala Thr Gly Ser 1745 1750 1755 1760 Tyr Asp Lys Ala Leu Arg Phe Leu Gly Ser Asn Asp Glu Glu Met Ser 1765 1770 1775 Tyr Asp Asn Asn Pro Tyr Ile Arg Ala Leu Val Asp Gly Cys Ala Thr 1780 1785 1790 Lys Lys Gly Tyr Gln Lys Thr Val Leu Glu Ile Asp Thr Pro Lys Val 1795 1800 1805 Glu Gln Val Pro Ile Val Asp Ile Met Phe Asn Asp Phe Gly Glu Ala 1810 1815 1820 Ser Gln Lys Phe Gly Phe Glu Val Gly Pro Ala Cys Phe Met Gly 1825 1830 1835 <210> 6 <211> 554 <212> PRT <213> Homo sapiens <400> 6 Met Ser Val Arg Tyr Ser Ser Ser Lys His Tyr Ser Ser Ser Arg Ser 1 5 10 15 Gly Gly Gly Gly Gly Gly Gly Gly Leu Ser Ser Leu Arg Ile Ser Ser 20 25 30 Ser Lys Gly Ser Leu Gly Gly Gly Phe Ser Ser Gly Gly Phe Ser Gly 35 40 45 Gly Ser Phe Ser Arg Gly Ser Ser Gly Gly Gly Cys Phe Gly Gly Ser 50 55 60 Ser Gly Gly Tyr Gly Gly Leu Gly Gly Phe Gly Gly Gly Ser Phe Arg 65 70 75 80 Gly Ser Tyr Gly Ser Ser Ser Phe Gly Gly Ser Tyr Gly Gly Ile Phe 85 90 95 Gly Gly Gly Ser Phe Gly Gly Gly Ser Phe Gly Gly Gly Ser Phe Gly 100 105 110 Gly Gly Gly Phe Gly Gly Gly Gly Phe Gly Gly Gly Phe Gly Gly Gly 115 120 125 Phe Gly Gly Asp Gly Gly Leu Leu Ser Gly Asn Glu Lys Val Thr Met 130 135 140 Gln Asn Leu Asn Asp Arg Leu Ala Ser Tyr Leu Asp Lys Val Arg Ala 145 150 155 160 Leu Glu Glu Ser Asn Tyr Glu Leu Glu Gly Lys Ile Lys Glu Trp Tyr 165 170 175 Glu Lys His Gly Asn Ser His Gln Gly Glu Pro Arg Asp Tyr Ser Lys 180 185 190 Tyr Tyr Lys Thr Ile Asp Asp Leu Lys Asn Gln Ile Leu Asn Leu Thr 195 200 205 Thr Asp Asn Ala Asn Ile Leu Leu Gln Ile Asp Asn Ala Arg Leu Ala 210 215 220 Ala Asp Asp Phe Arg Leu Lys Tyr Glu Asn Glu Val Ala Leu Arg Gln 225 230 235 240 Ser Val Glu Ala Asp Ile Asn Gly Leu Arg Arg Val Leu Asp Glu Leu 245 250 255 Thr Leu Thr Lys Ala Asp Leu Glu Met Gln Ile Glu Ser Leu Thr Glu 260 265 270 Glu Leu Ala Tyr Leu Lys Lys Asn His Glu Glu Glu Met Lys Asp Leu 275 280 285 Arg Asn Val Ser Thr Gly Asp Val Asn Val Glu Met Asn Ala Ala Pro 290 295 300 Gly Val Asp Leu Thr Gln Leu Leu Asn Asn Met Arg Ser Gln Tyr Glu 305 310 315 320 Gln Leu Ala Glu Gln Asn Arg Lys Asp Ala Glu Ala Trp Phe Asn Glu 325 330 335 Lys Ser Lys Glu Leu Thr Thr Glu Ile Asp Asn Asn Ile Glu Gln Ile 340 345 350 Ser Ser Tyr Lys Ser Glu Ile Thr Glu Leu Arg Arg Asn Val Gln Ala 355 360 365 Leu Glu Ile Glu Leu Gln Ser Gln Leu Ala Leu Lys Gln Ser Leu Glu 370 375 380 Ala Ser Leu Ala Glu Thr Glu Gly Arg Tyr Cys Val Gln Leu Ser Gln 385 390 395 400 Ile Gln Ala Gln Ile Ser Ala Leu Glu Glu Gln Leu Gln Gln Ile Arg 405 410 415 Ala Glu Thr Glu Cys Gln Asn Thr Glu Tyr Gln Gln Leu Leu Asp Ile 420 425 430 Lys Ile Arg Leu Glu Asn Glu Ile Gln Thr Tyr Arg Ser Leu Leu Glu 435 440 445 Gly Glu Gly Ser Ser Gly Gly Gly His Gly Gly Gly His Gly Gly Ser 450 455 460 Ser Gly Gly Gly Tyr Gly Gly Gly Ser Ser Gly Gly Gly Ser Ser Gly 465 470 475 480 Gly Gly Tyr Gly Gly Gly Ser Ser Ser Gly Gly His Gly Gly Ser Ser 485 490 495 Ser Gly Gly Tyr Gly Gly Gly Ser Ser Gly Gly Gly Gly Gly Gly Tyr 500 505 510 Gly Gly Gly Ser Ser Gly Gly Gly Ser Ser Ser Gly Gly Gly Tyr Gly 515 520 525 Gly Gly Ser Ser Ser Gly Gly His Lys Ser Ser Ser Ser Gly Ser Val 530 535 540 Gly Glu Ser Ser Ser Lys Gly Pro Arg Ser 545 550 <210> 7 <211> 846 <212> PRT <213> Homo sapiens <400> 7 Met Phe Ser Val Val Asp Glu Asn Phe Ser Trp Tyr Leu Glu Asp Asn 1 5 10 15 Ile Lys Thr Tyr Cys Ser Glu Pro Glu Lys Val Asp Lys Asp Asn Glu 20 25 30 Asp Phe Gln Glu Ser Asn Arg Met Tyr Ser Val Asn Gly Tyr Thr Phe 35 40 45 Gly Ser Leu Pro Gly Leu Ser Met Cys Ala Glu Asp Arg Val Lys Trp 50 55 60 Tyr Leu Phe Gly Met Gly Asn Glu Val Asp Val His Ala Ala Phe Phe 65 70 75 80 His Gly Gln Ala Leu Thr Asn Lys Asn Tyr Arg Ile Asp Thr Ile Asn 85 90 95 Leu Phe Pro Ala Thr Leu Phe Asp Ala Tyr Met Val Ala Gln Asn Pro 100 105 110 Gly Glu Trp Met Leu Ser Cys Gln Asn Leu Asn His Leu Lys Ala Gly 115 120 125 Leu Gln Ala Phe Phe Gln Val Gln Glu Cys Asn Lys Ser Ser Ser Lys 130 135 140 Asp Asn Ile Arg Gly Lys His Val Arg His Tyr Tyr Ile Ala Ala Glu 145 150 155 160 Glu Ile Ile Trp Asn Tyr Ala Pro Ser Gly Ile Asp Ile Phe Thr Lys 165 170 175 Glu Asn Leu Thr Ala Pro Gly Ser Asp Ser Ala Val Phe Phe Glu Gln 180 185 190 Gly Thr Thr Arg Ile Gly Gly Ser Tyr Lys Lys Leu Val Tyr Arg Glu 195 200 205 Tyr Thr Asp Ala Ser Phe Thr Asn Arg Lys Glu Arg Gly Pro Glu Glu 210 215 220 Glu His Leu Gly Ile Leu Gly Pro Val Ile Trp Ala Glu Val Gly Asp 225 230 235 240 Thr Ile Arg Val Thr Phe His Asn Lys Gly Ala Tyr Pro Leu Ser Ile 245 250 255 Glu Pro Ile Gly Val Arg Phe Asn Lys Asn Asn Glu Gly Thr Tyr Tyr 260 265 270 Ser Pro Asn Tyr Asn Pro Gln Ser Arg Ser Val Pro Pro Ser Ala Ser 275 280 285 His Val Ala Pro Thr Glu Thr Phe Thr Tyr Glu Trp Thr Val Pro Lys 290 295 300 Glu Val Gly Pro Thr Asn Ala Asp Pro Val Cys Leu Ala Lys Met Tyr 305 310 315 320 Tyr Ser Ala Val Glu Pro Thr Lys Asp Ile Phe Thr Gly Leu Ile Gly 325 330 335 Pro Met Lys Ile Cys Lys Lys Gly Ser Leu His Ala Asn Gly Arg Gln 340 345 350 Lys Asp Val Asp Lys Glu Phe Tyr Leu Phe Pro Thr Val Phe Asp Glu 355 360 365 Asn Glu Ser Leu Leu Leu Glu Asp Asn Ile Arg Met Phe Thr Thr Ala 370 375 380 Pro Asp Gln Val Asp Lys Glu Asp Glu Asp Phe Gln Glu Ser Asn Lys 385 390 395 400 Met His Ser Met Asn Gly Phe Met Tyr Gly Asn Gln Pro Gly Leu Thr 405 410 415 Met Cys Lys Gly Asp Ser Val Val Trp Tyr Leu Phe Ser Ala Gly Asn 420 425 430 Glu Ala Asp Val His Gly Ile Tyr Phe Ser Gly Asn Thr Tyr Leu Trp 435 440 445 Arg Gly Glu Arg Arg Asp Thr Ala Asn Leu Phe Pro Gln Thr Ser Leu 450 455 460 Thr Leu His Met Trp Pro Asp Thr Glu Gly Thr Phe Asn Val Glu Cys 465 470 475 480 Leu Thr Thr Asp His Tyr Thr Gly Gly Met Lys Gln Lys Tyr Thr Val 485 490 495 Asn Gln Cys Arg Arg Gln Ser Glu Asp Ser Thr Phe Tyr Leu Gly Glu 500 505 510 Arg Thr Tyr Tyr Ile Ala Ala Val Glu Val Glu Trp Asp Tyr Ser Pro 515 520 525 Gln Arg Glu Trp Glu Lys Glu Leu His His Leu Gln Glu Gln Asn Val 530 535 540 Ser Asn Ala Phe Leu Asp Lys Gly Glu Phe Tyr Ile Gly Ser Lys Tyr 545 550 555 560 Lys Lys Val Val Tyr Arg Gln Tyr Thr Asp Ser Thr Phe Arg Val Pro 565 570 575 Val Glu Arg Lys Ala Glu Glu Glu His Leu Gly Ile Leu Gly Pro Gln 580 585 590 Leu His Ala Asp Val Gly Asp Lys Val Lys Ile Ile Phe Lys Asn Met 595 600 605 Ala Thr Arg Pro Tyr Ser Ile His Ala His Gly Val Gln Thr Glu Ser 610 615 620 Ser Thr Val Thr Pro Thr Leu Pro Gly Glu Thr Leu Thr Tyr Val Trp 625 630 635 640 Lys Ile Pro Glu Arg Ser Gly Ala Gly Thr Glu Asp Ser Ala Cys Ile 645 650 655 Pro Trp Ala Tyr Tyr Ser Thr Val Asp Gln Val Lys Asp Leu Tyr Ser 660 665 670 Gly Leu Ile Gly Pro Leu Ile Val Cys Arg Arg Pro Tyr Leu Lys Val 675 680 685 Phe Asn Pro Arg Arg Lys Leu Glu Phe Ala Leu Leu Phe Leu Val Phe 690 695 700 Asp Glu Asn Glu Ser Trp Tyr Leu Asp Asp Asn Ile Lys Thr Tyr Ser 705 710 715 720 Asp His Pro Glu Lys Val Asn Lys Asp Asp Glu Glu Phe Ile Glu Ser 725 730 735 Asn Lys Met His Ala Ile Asn Gly Arg Met Phe Gly Asn Leu Gln Gly 740 745 750 Leu Thr Met His Val Gly Asp Glu Val Asn Trp Tyr Leu Met Gly Met 755 760 765 Gly Asn Glu Ile Asp Leu His Thr Val His Phe His Gly His Ser Phe 770 775 780 Gln Tyr Lys His Arg Gly Val Tyr Ser Ser Asp Val Phe Asp Ile Phe 785 790 795 800 Pro Gly Thr Tyr Gln Thr Leu Glu Met Phe Pro Arg Thr Pro Gly Ile 805 810 815 Trp Leu Leu His Cys His Val Thr Asp His Ile His Ala Gly Met Glu 820 825 830 Thr Thr Tyr Thr Val Leu Gln Asn Glu Asp Thr Lys Ser Gly 835 840 845 <210> 8 <211> 244 <212> PRT <213> Homo sapiens <400> 8 Met Leu Leu Leu Gly Ala Val Leu Leu Leu Leu Ala Leu Pro Gly His 1 5 10 15 Asp Gln Glu Thr Thr Thr Gln Gly Pro Gly Val Leu Leu Pro Leu Pro 20 25 30 Lys Gly Ala Cys Thr Gly Trp Met Ala Gly Ile Pro Gly His Pro Gly 35 40 45 His Asn Gly Ala Pro Gly Arg Asp Gly Arg Asp Gly Thr Pro Gly Glu 50 55 60 Lys Gly Glu Lys Gly Asp Pro Gly Leu Ile Gly Pro Lys Gly Asp Ile 65 70 75 80 Gly Glu Thr Gly Val Pro Gly Ala Glu Gly Pro Arg Gly Phe Pro Gly 85 90 95 Ile Gln Gly Arg Lys Gly Glu Pro Gly Glu Gly Ala Tyr Val Tyr Arg 100 105 110 Ser Ala Phe Ser Val Gly Leu Glu Thr Tyr Val Thr Ile Pro Asn Met 115 120 125 Pro Ile Arg Phe Thr Lys Ile Phe Tyr Asn Gln Gln Asn His Tyr Asp 130 135 140 Gly Ser Thr Gly Lys Phe His Cys Asn Ile Pro Gly Leu Tyr Tyr Phe 145 150 155 160 Ala Tyr His Ile Thr Val Tyr Met Lys Asp Val Lys Val Ser Leu Phe 165 170 175 Lys Lys Asp Lys Ala Met Leu Phe Thr Tyr Asp Gln Tyr Gln Glu Asn 180 185 190 Asn Val Asp Gln Ala Ser Gly Ser Val Leu Leu His Leu Glu Val Gly 195 200 205 Asp Gln Val Trp Leu Gln Val Tyr Gly Glu Gly Glu Arg Asn Gly Leu 210 215 220 Tyr Ala Asp Asn Asp Asn Asp Ser Thr Phe Thr Gly Phe Leu Leu Tyr 225 230 235 240 His Asp Thr Asn <210> 9 <211> 180 <212> PRT <213> Homo sapiens <400> 9 Gly Asn Ile Phe Ala Asn Leu Phe Lys Gly Leu Phe Gly Lys Lys Glu 1 5 10 15 Met Arg Ile Leu Met Val Gly Leu Asp Ala Ala Gly Lys Thr Thr Ile 20 25 30 Leu Tyr Lys Leu Lys Leu Gly Glu Ile Val Thr Thr Ile Pro Thr Ile 35 40 45 Gly Phe Asn Val Glu Thr Val Glu Tyr Lys Asn Ile Ser Phe Thr Val 50 55 60 Trp Asp Val Gly Gly Gln Asp Lys Ile Arg Pro Leu Trp Arg His Tyr 65 70 75 80 Phe Gln Asn Thr Gln Gly Leu Ile Phe Val Val Asp Ser Asn Asp Arg 85 90 95 Glu Arg Val Asn Glu Ala Arg Glu Glu Leu Met Arg Met Leu Ala Glu 100 105 110 Asp Glu Leu Arg Asp Ala Val Leu Leu Val Phe Ala Asn Lys Gln Asp 115 120 125 Leu Pro Asn Ala Met Asn Ala Ala Glu Ile Thr Asp Lys Leu Gly Leu 130 135 140 His Ser Leu Arg His Arg Asn Trp Tyr Ile Gln Ala Thr Cys Ala Thr 145 150 155 160 Ser Gly Asp Gly Leu Tyr Glu Gly Leu Asp Trp Leu Ser Asn Gln Leu 165 170 175 Arg Asn Gln Lys 180 <210> 10 <211> 3388 <212> PRT <213> Homo sapiens <400> 10 Met Ala Ala Ala Ala Arg Pro Arg Gly Arg Ala Leu Gly Pro Val Leu 1 5 10 15 Pro Pro Thr Pro Leu Leu Leu Leu Val Leu Arg Val Leu Pro Ala Cys 20 25 30 Gly Ala Thr Ala Arg Asp Pro Gly Ala Ala Ala Gly Leu Ser Leu His 35 40 45 Pro Thr Tyr Phe Asn Leu Ala Glu Ala Ala Arg Ile Trp Ala Thr Ala 50 55 60 Thr Cys Gly Glu Arg Gly Pro Gly Glu Gly Arg Pro Gln Pro Glu Leu 65 70 75 80 Tyr Cys Lys Leu Val Gly Gly Pro Thr Ala Pro Gly Ser Gly His Thr 85 90 95 Ile Gln Gly Gln Phe Cys Asp Tyr Cys Asn Ser Glu Asp Pro Arg Lys 100 105 110 Ala His Pro Val Thr Asn Ala Ile Asp Gly Ser Glu Arg Trp Trp Gln 115 120 125 Ser Pro Pro Leu Ser Ser Gly Thr Gln Tyr Asn Arg Val Asn Leu Thr 130 135 140 Leu Asp Leu Gly Gln Leu Phe His Val Ala Tyr Ile Leu Ile Lys Phe 145 150 155 160 Ala Asn Ser Pro Arg Pro Asp Leu Trp Val Leu Glu Arg Ser Val Asp 165 170 175 Phe Gly Ser Thr Tyr Ser Pro Trp Gln Tyr Phe Ala His Ser Lys Val 180 185 190 Asp Cys Leu Lys Glu Phe Gly Arg Glu Ala Asn Met Ala Val Thr Arg 195 200 205 Asp Asp Asp Val Leu Cys Val Thr Glu Tyr Ser Arg Ile Val Pro Leu 210 215 220 Glu Asn Gly Glu Val Val Val Ser Leu Ile Asn Gly Arg Pro Gly Ala 225 230 235 240 Lys Asn Phe Thr Phe Ser His Thr Leu Arg Glu Phe Thr Lys Ala Thr 245 250 255 Asn Ile Arg Leu Arg Phe Leu Arg Thr Asn Thr Leu Leu Gly His Leu 260 265 270 Ile Ser Lys Ala Gln Arg Asp Pro Thr Val Thr Arg Arg Tyr Tyr Tyr 275 280 285 Ser Ile Lys Asp Ile Ser Ile Gly Gly Gln Cys Val Cys Asn Gly His 290 295 300 Ala Glu Val Cys Asn Ile Asn Asn Pro Glu Lys Leu Phe Arg Cys Glu 305 310 315 320 Cys Gln His His Thr Cys Gly Glu Thr Cys Asp Arg Cys Cys Thr Gly 325 330 335 Tyr Asn Gln Arg Arg Trp Arg Pro Ala Ala Trp Glu Gln Ser His Glu 340 345 350 Cys Glu Ala Cys Asn Cys His Gly His Ala Ser Asn Cys Tyr Tyr Asp 355 360 365 Pro Asp Val Glu Arg Gln Gln Ala Ser Leu Asn Thr Gln Gly Ile Tyr 370 375 380 Ala Gly Gly Gly Val Cys Ile Asn Cys Gln His Asn Thr Ala Gly Val 385 390 395 400 Asn Cys Glu Gln Cys Ala Lys Gly Tyr Tyr Arg Pro Tyr Gly Val Pro 405 410 415 Val Asp Ala Pro Asp Gly Cys Ile Pro Cys Ser Cys Asp Pro Glu His 420 425 430 Ala Asp Gly Cys Glu Gln Gly Ser Gly Arg Cys His Cys Lys Pro Asn 435 440 445 Phe His Gly Asp Asn Cys Glu Lys Cys Ala Ile Gly Tyr Tyr Asn Phe 450 455 460 Pro Phe Cys Leu Arg Ile Pro Ile Phe Pro Val Ser Thr Pro Ser Ser 465 470 475 480 Glu Asp Pro Val Ala Gly Asp Ile Lys Gly Asn Phe Leu Ser Ser Ala 485 490 495 Gly Cys Asp Cys Asn Leu Glu Gly Val Leu Pro Glu Ile Cys Asp Ala 500 505 510 His Gly Arg Cys Leu Cys Arg Pro Gly Val Glu Gly Pro Arg Cys Asp 515 520 525 Thr Cys Arg Ser Gly Phe Tyr Ser Phe Pro Ile Cys Gln Ala Cys Trp 530 535 540 Cys Ser Ala Leu Gly Ser Tyr Gln Met Pro Cys Ser Ser Val Thr Gly 545 550 555 560 Gln Cys Glu Cys Arg Pro Gly Val Thr Gly Gln Arg Cys Asp Arg Cys 565 570 575 Leu Ser Gly Ala Tyr Asp Phe Pro His Cys Gln Gly Ser Ser Ser Ala 580 585 590 Cys Asp Pro Ala Gly Thr Ile Asn Ser Asn Leu Gly Tyr Cys Gln Cys 595 600 605 Lys Leu His Val Glu Gly Pro Thr Cys Ser Arg Cys Lys Leu Leu Tyr 610 615 620 Trp Asn Leu Asp Lys Glu Asn Pro Ser Gly Cys Ser Glu Cys Lys Cys 625 630 635 640 His Lys Ala Gly Thr Val Ser Gly Thr Gly Glu Cys Arg Gln Gly Asp 645 650 655 Gly Asp Cys His Cys Lys Ser His Val Gly Gly Asp Ser Cys Asp Thr 660 665 670 Cys Glu Asp Gly Tyr Phe Ala Leu Glu Lys Ser Asn Tyr Phe Gly Cys 675 680 685 Gln Gly Cys Gln Cys Asp Ile Gly Gly Ala Leu Ser Ser Met Cys Ser 690 695 700 Gly Pro Ser Gly Val Cys Gln Cys Arg Glu His Val Val Gly Lys Val 705 710 715 720 Cys Gln Arg Pro Glu Asn Asn Tyr Tyr Phe Pro Asp Leu His His Met 725 730 735 Lys Tyr Glu Ile Glu Asp Gly Ser Thr Pro Asn Gly Arg Asp Leu Arg 740 745 750 Phe Gly Phe Asp Pro Leu Ala Phe Pro Glu Phe Ser Trp Arg Gly Tyr 755 760 765 Ala Gln Met Thr Ser Val Gln Asn Asp Val Arg Ile Thr Leu Asn Val 770 775 780 Gly Lys Ser Ser Gly Ser Leu Phe Arg Val Ile Leu Arg Tyr Val Asn 785 790 795 800 Pro Gly Thr Glu Ala Val Ser Gly His Ile Thr Ile Tyr Pro Ser Trp 805 810 815 Gly Ala Ala Gln Ser Lys Glu Ile Ile Phe Leu Pro Ser Lys Glu Pro 820 825 830 Ala Phe Val Thr Val Pro Gly Asn Gly Phe Ala Asp Pro Phe Ser Ile 835 840 845 Thr Pro Gly Ile Trp Val Ala Cys Ile Lys Ala Glu Gly Val Leu Leu 850 855 860 Asp Tyr Leu Val Leu Leu Pro Arg Asp Tyr Tyr Glu Ala Ser Val Leu 865 870 875 880 Gln Leu Pro Val Thr Glu Pro Cys Ala Tyr Ala Gly Pro Pro Gln Glu 885 890 895 Asn Cys Leu Leu Tyr Gln His Leu Pro Val Thr Arg Phe Pro Cys Thr 900 905 910 Leu Ala Cys Glu Ala Arg His Phe Leu Leu Asp Gly Glu Pro Arg Pro 915 920 925 Val Ala Val Arg Gln Pro Thr Pro Ala His Pro Val Met Val Asp Leu 930 935 940 Ser Gly Arg Glu Val Glu Leu His Leu Arg Leu Arg Ile Pro Gln Val 945 950 955 960 Gly His Tyr Val Val Val Val Glu Tyr Ser Thr Glu Ala Ala Gln Leu 965 970 975 Phe Val Val Asp Val Asn Val Lys Ser Ser Gly Ser Val Leu Ala Gly 980 985 990 Gln Val Asn Ile Tyr Ser Cys Asn Tyr Ser Val Leu Cys Arg Ser Ala 995 1000 1005 Val Ile Asp His Met Ser Arg Ile Ala Met Tyr Glu Leu Leu Ala Asp 1010 1015 1020 Ala Asp Ile Gln Leu Lys Gly His Met Ala Arg Phe Leu Leu His Gln 1025 1030 1035 1040 Val Cys Ile Ile Pro Ile Glu Glu Phe Ser Ala Glu Tyr Val Arg Pro 1045 1050 1055 Gln Val His Cys Ile Ala Ser Tyr Gly Arg Phe Val Asn Gln Ser Ala 1060 1065 1070 Thr Cys Val Ser Leu Ala His Glu Thr Pro Pro Thr Ala Leu Ile Leu 1075 1080 1085 Asp Val Leu Ser Gly Arg Pro Phe Pro His Leu Pro Gln Gln Ser Ser 1090 1095 1100 Pro Ser Val Asp Val Leu Pro Gly Val Thr Leu Lys Ala Pro Gln Asn 1105 1110 1115 1120 Gln Val Thr Leu Arg Gly Arg Val Pro His Leu Gly Arg Tyr Val Phe 1125 1130 1135 Val Ile His Phe Tyr Gln Ala Ala His Pro Thr Phe Pro Ala Gln Val 1140 1145 1150 Ser Val Asp Gly Gly Trp Pro Arg Ala Gly Ser Phe His Ala Ser Phe 1155 1160 1165 Cys Pro His Val Leu Gly Cys Arg Asp Gln Val Ile Ala Glu Gly Gln 1170 1175 1180 Ile Glu Phe Asp Ile Ser Glu Pro Glu Val Ala Ala Thr Val Lys Val 1185 1190 1195 1200 Pro Glu Gly Lys Ser Leu Val Leu Val Arg Val Leu Val Val Pro Ala 1205 1210 1215 Glu Asn Tyr Asp Tyr Gln Ile Leu His Lys Lys Ser Met Asp Lys Ser 1220 1225 1230 Leu Glu Phe Ile Thr Asn Cys Gly Lys Asn Ser Phe Tyr Leu Asp Pro 1235 1240 1245 Gln Thr Ala Ser Arg Phe Cys Lys Asn Ser Ala Arg Ser Leu Val Ala 1250 1255 1260 Phe Tyr His Lys Gly Ala Leu Pro Cys Glu Cys His Pro Thr Gly Ala 1265 1270 1275 1280 Thr Gly Pro His Cys Ser Pro Glu Gly Gly Gln Cys Pro Cys Gln Pro 1285 1290 1295 Asn Val Ile Gly Arg Gln Cys Thr Arg Cys Ala Thr Gly His Tyr Gly 1300 1305 1310 Phe Pro Arg Cys Lys Arg Lys Cys Thr Cys Gly Arg Arg Leu Cys Glu 1315 1320 1325 Glu Met Thr Gly Gln Cys Arg Cys Pro Pro Arg Thr Val Arg Pro Gln 1330 1335 1340 Cys Glu Val Cys Glu Thr His Ser Phe Ser Phe His Pro Met Ala Gly 1345 1350 1355 1360 Cys Glu Gly Cys Asn Cys Ser Arg Arg Gly Thr Ile Glu Ala Ala Met 1365 1370 1375 Pro Glu Cys Asp Arg Asp Ser Gly Gln Cys Arg Cys Lys Pro Arg Ile 1380 1385 1390 Thr Gly Arg Gln Cys Asp Arg Cys Ala Ser Gly Phe Tyr Arg Phe Pro 1395 1400 1405 Glu Cys Val Pro Cys Asn Cys Asn Arg Asp Gly Thr Glu Pro Gly Val 1410 1415 1420 Cys Asp Pro Gly Thr Gly Ala Cys Leu Cys Lys Glu Asn Val Glu Gly 1425 1430 1435 1440 Thr Glu Cys Asn Val Cys Arg Glu Gly Ser Phe His Leu Asp Pro Ala 1445 1450 1455 Asn Leu Lys Gly Cys Thr Ser Cys Phe Cys Phe Gly Val Asn Asn Gln 1460 1465 1470 Cys His Ser Ser His Lys Arg Arg Thr Lys Phe Val Asp Met Leu Gly 1475 1480 1485 Trp His Leu Glu Thr Ala Asp Arg Val Asp Ile Pro Val Ser Phe Asn 1490 1495 1500 Pro Gly Ser Asn Ser Met Val Ala Asp Leu Gln Glu Leu Pro Ala Thr 1505 1510 1515 1520 Ile His Ser Ala Ser Trp Val Ala Pro Thr Ser Tyr Leu Gly Asp Lys 1525 1530 1535 Val Ser Ser Tyr Gly Gly Tyr Leu Thr Tyr Gln Ala Lys Ser Phe Gly 1540 1545 1550 Leu Pro Gly Asp Met Val Leu Leu Glu Lys Lys Pro Asp Val Gln Leu 1555 1560 1565 Thr Gly Gln His Met Ser Ile Ile Tyr Glu Glu Thr Asn Thr Pro Arg 1570 1575 1580 Pro Asp Arg Leu His His Gly Arg Val His Val Val Glu Gly Asn Phe 1585 1590 1595 1600 Arg His Ala Ser Ser Arg Ala Pro Val Ser Arg Glu Glu Leu Met Thr 1605 1610 1615 Val Leu Ser Arg Leu Ala Asp Val Arg Ile Gln Gly Leu Tyr Phe Thr 1620 1625 1630 Glu Thr Gln Arg Leu Thr Leu Ser Glu Val Gly Leu Glu Glu Ala Ser 1635 1640 1645 Asp Thr Gly Ser Gly Arg Ile Ala Leu Ala Val Glu Ile Cys Ala Cys 1650 1655 1660 Pro Pro Ala Tyr Ala Gly Asp Ser Ser Cys Ser Met Gly Trp Leu Trp 1665 1670 1675 1680 Ile Phe Gly Ala Ala Leu Gly Gln Cys Leu Gly Tyr Ser Ser Gln Gln 1685 1690 1695 Gln Arg Val Pro Phe Leu Gln Pro Pro Gly Gln Ser Gln Leu Gln Ala 1700 1705 1710 Ser Tyr Val Glu Phe Arg Pro Ser Gln Gly Cys Ser Pro Gly Tyr Tyr 1715 1720 1725 Arg Asp His Lys Gly Leu Tyr Thr Gly Arg Cys Val Pro Cys Asn Cys 1730 1735 1740 Asn Gly His Ser Asn Gln Cys Gln Asp Gly Ser Gly Ile Cys Val Asn 1745 1750 1755 1760 Cys Gln His Asn Thr Ala Gly Glu His Cys Glu Arg Cys Gln Glu Gly 1765 1770 1775 Tyr Tyr Gly Asn Ala Val His Gly Ser Cys Arg Ala Cys Pro Cys Pro 1780 1785 1790 His Thr Asn Ser Phe Ala Thr Gly Cys Val Val Asn Gly Gly Asp Val 1795 1800 1805 Arg Cys Ser Cys Lys Ala Gly Tyr Thr Gly Thr Gln Cys Glu Arg Cys 1810 1815 1820 Ala Pro Gly Tyr Phe Gly Asn Pro Gln Lys Phe Gly Gly Ser Cys Gln 1825 1830 1835 1840 Pro Cys Ser Cys Asn Ser Asn Gly Gln Leu Gly Ser Cys His Pro Leu 1845 1850 1855 Thr Gly Asp Cys Ile Asn Gln Glu Pro Lys Asp Ser Ser Pro Ala Glu 1860 1865 1870 Glu Cys Asp Asp Cys Asp Ser Cys Val Met Thr Leu Leu Asn Asp Leu 1875 1880 1885 Ala Thr Met Gly Glu Gln Leu Arg Leu Val Lys Ser Gln Leu Gln Gly 1890 1895 1900 Leu Ser Ala Ser Ala Gly Leu Leu Glu Gln Met Arg His Met Glu Thr 1905 1910 1915 1920 Gln Ala Lys Asp Leu Arg Asn Gln Leu Leu Asn Tyr Arg Ser Ala Ile 1925 1930 1935 Ser Asn His Gly Ser Lys Ile Glu Gly Leu Glu Arg Glu Leu Thr Asp 1940 1945 1950 Leu Asn Gln Glu Phe Glu Thr Leu Gln Glu Lys Ala Gln Val Asn Ser 1955 1960 1965 Arg Lys Ala Gln Thr Leu Asn Asn Asn Val Asn Arg Ala Thr Gln Ser 1970 1975 1980 Ala Lys Glu Leu Asp Val Lys Ile Lys Asn Val Ile Arg Asn Val His 1985 1990 1995 2000 Ile Leu Leu Lys Gln Ile Ser Gly Thr Asp Gly Glu Gly Asn Asn Val 2005 2010 2015 Pro Ser Gly Asp Phe Ser Arg Glu Trp Ala Glu Ala Gln Arg Met Met 2020 2025 2030 Arg Glu Leu Arg Asn Arg Asn Phe Gly Lys His Leu Arg Glu Ala Glu 2035 2040 2045 Ala Asp Lys Arg Glu Ser Gln Leu Leu Leu Asn Arg Ile Arg Thr Trp 2050 2055 2060 Gln Lys Thr His Gln Gly Glu Asn Asn Gly Leu Ala Asn Ser Ile Arg 2065 2070 2075 2080 Asp Ser Leu Asn Glu Tyr Glu Ala Lys Leu Ser Asp Leu Arg Ala Arg 2085 2090 2095 Leu Gln Glu Ala Ala Ala Gln Ala Lys Gln Ala Asn Gly Leu Asn Gln 2100 2105 2110 Glu Asn Glu Arg Ala Leu Gly Ala Ile Gln Arg Gln Val Lys Glu Ile 2115 2120 2125 Asn Ser Leu Gln Ser Asp Phe Thr Lys Tyr Leu Thr Thr Ala Asp Ser 2130 2135 2140 Ser Leu Leu Gln Thr Asn Ile Ala Leu Gln Leu Met Glu Lys Ser Gln 2145 2150 2155 2160 Lys Glu Tyr Glu Lys Leu Ala Ala Ser Leu Asn Glu Ala Arg Gln Glu 2165 2170 2175 Leu Ser Asp Lys Val Arg Glu Leu Ser Arg Ser Ala Gly Lys Thr Ser 2180 2185 2190 Leu Val Glu Glu Ala Glu Lys His Ala Arg Ser Leu Gln Glu Leu Ala 2195 2200 2205 Lys Gln Leu Glu Glu Ile Lys Arg Asn Ala Ser Gly Asp Glu Leu Val 2210 2215 2220 Arg Cys Ala Val Asp Ala Ala Thr Ala Tyr Glu Asn Ile Leu Asn Ala 2225 2230 2235 2240 Ile Lys Ala Ala Glu Asp Ala Ala Asn Arg Ala Ala Ser Ala Ser Glu 2245 2250 2255 Ser Ala Leu Gln Thr Val Ile Lys Glu Asp Leu Pro Arg Lys Ala Lys 2260 2265 2270 Thr Leu Ser Ser Asn Ser Asp Lys Leu Leu Asn Glu Ala Lys Met Thr 2275 2280 2285 Gln Lys Lys Leu Lys Gln Glu Val Ser Pro Ala Leu Asn Asn Leu Gln 2290 2295 2300 Gln Thr Leu Asn Ile Val Thr Val Gln Lys Glu Val Ile Asp Thr Asn 2305 2310 2315 2320 Leu Thr Thr Leu Arg Asp Gly Leu His Gly Ile Gln Arg Gly Asp Ile 2325 2330 2335 Asp Ala Met Ile Ser Ser Ala Lys Ser Met Val Arg Lys Ala Asn Asp 2340 2345 2350 Ile Thr Asp Glu Val Leu Asp Gly Leu Asn Pro Ile Gln Thr Asp Val 2355 2360 2365 Glu Arg Ile Lys Asp Thr Tyr Gly Arg Thr Gln Asn Glu Asp Phe Lys 2370 2375 2380 Lys Ala Leu Thr Asp Ala Asp Asn Ser Val Asn Lys Leu Thr Asn Lys 2385 2390 2395 2400 Leu Pro Asp Leu Trp Arg Lys Ile Glu Ser Ile Asn Gln Gln Leu Leu 2405 2410 2415 Pro Leu Gly Asn Ile Ser Asp Asn Met Asp Arg Ile Arg Glu Leu Ile 2420 2425 2430 Gln Gln Ala Arg Asp Ala Ala Ser Lys Val Ala Val Pro Met Arg Phe 2435 2440 2445 Asn Gly Lys Ser Gly Val Glu Val Arg Leu Pro Asn Asp Leu Glu Asp 2450 2455 2460 Leu Lys Gly Tyr Thr Ser Leu Ser Leu Phe Leu Gln Arg Pro Asn Ser 2465 2470 2475 2480 Arg Glu Asn Gly Gly Thr Glu Asn Met Phe Val Met Tyr Leu Gly Asn 2485 2490 2495 Lys Asp Ala Ser Arg Asp Tyr Ile Gly Met Ala Val Val Asp Gly Gln 2500 2505 2510 Leu Thr Cys Val Tyr Asn Leu Gly Asp Arg Glu Ala Glu Leu Gln Val 2515 2520 2525 Asp Gln Ile Leu Thr Lys Ser Glu Thr Lys Glu Ala Val Met Asp Arg 2530 2535 2540 Val Lys Phe Gln Arg Ile Tyr Gln Phe Ala Arg Leu Asn Tyr Thr Lys 2545 2550 2555 2560 Gly Ala Thr Ser Ser Lys Pro Glu Thr Pro Gly Val Tyr Asp Met Asp 2565 2570 2575 Gly Arg Asn Ser Asn Thr Leu Leu Asn Leu Asp Pro Glu Asn Val Val 2580 2585 2590 Phe Tyr Val Gly Gly Tyr Pro Pro Asp Phe Lys Leu Pro Ser Arg Leu 2595 2600 2605 Ser Phe Pro Pro Tyr Lys Gly Cys Ile Glu Leu Asp Asp Leu Asn Glu 2610 2615 2620 Asn Val Leu Ser Leu Tyr Asn Phe Lys Lys Thr Phe Asn Leu Asn Thr 2625 2630 2635 2640 Thr Glu Val Glu Pro Cys Arg Arg Arg Lys Glu Glu Ser Asp Lys Asn 2645 2650 2655 Tyr Phe Glu Gly Thr Gly Tyr Ala Arg Val Pro Thr Gln Pro His Ala 2660 2665 2670 Pro Ile Pro Thr Phe Gly Gln Thr Ile Gln Thr Thr Val Asp Arg Gly 2675 2680 2685 Leu Leu Phe Phe Ala Glu Asn Gly Asp Arg Phe Ile Ser Leu Asn Ile 2690 2695 2700 Glu Asp Gly Lys Leu Met Val Arg Tyr Lys Leu Asn Ser Glu Leu Pro 2705 2710 2715 2720 Lys Glu Arg Gly Val Gly Asp Ala Ile Asn Asn Gly Arg Asp His Ser 2725 2730 2735 Ile Gln Ile Lys Ile Gly Lys Leu Gln Lys Arg Met Trp Ile Asn Val 2740 2745 2750 Asp Val Gln Asn Thr Ile Ile Asp Gly Glu Val Phe Asp Phe Ser Thr 2755 2760 2765 Tyr Tyr Leu Gly Gly Ile Pro Ile Ala Ile Arg Glu Arg Phe Asn Ile 2770 2775 2780 Ser Thr Pro Ala Phe Arg Gly Cys Met Lys Asn Leu Lys Lys Thr Ser 2785 2790 2795 2800 Gly Val Val Arg Leu Asn Asp Thr Val Gly Val Thr Lys Lys Cys Ser 2805 2810 2815 Glu Asp Trp Lys Leu Val Arg Ser Ala Ser Phe Ser Arg Gly Gly Gln 2820 2825 2830 Leu Ser Phe Thr Asp Leu Gly Leu Pro Pro Thr Asp His Leu Gln Ala 2835 2840 2845 Ser Phe Gly Phe Gln Thr Phe Gln Pro Ser Gly Ile Leu Leu Asp His 2850 2855 2860 Gln Thr Trp Thr Arg Asn Leu Gln Val Thr Leu Glu Asp Gly Tyr Ile 2865 2870 2875 2880 Glu Leu Ser Thr Ser Asp Ser Gly Ser Pro Ile Phe Lys Ser Pro Gln 2885 2890 2895 Thr Tyr Met Asp Gly Leu Leu His Tyr Val Ser Val Ile Ser Asp Asn 2900 2905 2910 Ser Gly Leu Arg Leu Leu Ile Asp Asp Gln Leu Leu Arg Asn Ser Lys 2915 2920 2925 Arg Leu Lys His Ile Ser Ser Ser Arg Gln Ser Leu Arg Leu Gly Gly 2930 2935 2940 Ser Asn Phe Glu Gly Cys Ile Ser Asn Val Phe Val Gln Arg Leu Ser 2945 2950 2955 2960 Leu Ser Pro Glu Val Leu Asp Leu Thr Ser Asn Ser Leu Lys Arg Asp 2965 2970 2975 Val Ser Leu Gly Gly Cys Ser Leu Asn Lys Pro Pro Phe Leu Met Leu 2980 2985 2990 Leu Lys Gly Ser Thr Arg Phe Asn Lys Thr Lys Thr Phe Arg Ile Asn 2995 3000 3005 Gln Leu Leu Gln Asp Thr Pro Val Ala Ser Pro Arg Ser Val Lys Val 3010 3015 3020 Trp Gln Asp Ala Cys Ser Pro Leu Pro Lys Thr Gln Ala Asn His Gly 3025 3030 3035 3040 Ala Leu Gln Phe Gly Asp Ile Pro Thr Ser His Leu Leu Phe Lys Leu 3045 3050 3055 Pro Gln Glu Leu Leu Lys Pro Arg Ser Gln Phe Ala Val Asp Met Gln 3060 3065 3070 Thr Thr Ser Ser Arg Gly Leu Val Phe His Thr Gly Thr Lys Asn Ser 3075 3080 3085 Phe Met Ala Leu Tyr Leu Ser Lys Gly Arg Leu Val Phe Ala Leu Gly 3090 3095 3100 Thr Asp Gly Lys Lys Leu Arg Ile Lys Ser Lys Glu Lys Cys Asn Asp 3105 3110 3115 3120 Gly Lys Trp His Thr Val Val Phe Gly His Asp Gly Glu Lys Gly Arg 3125 3130 3135 Leu Val Val Asp Gly Leu Arg Ala Arg Glu Gly Ser Leu Pro Gly Asn 3140 3145 3150 Ser Thr Ile Ser Ile Arg Ala Pro Val Tyr Leu Gly Ser Pro Pro Ser 3155 3160 3165 Gly Lys Pro Lys Ser Leu Pro Thr Asn Ser Phe Val Gly Cys Leu Lys 3170 3175 3180 Asn Phe Gln Leu Asp Ser Lys Pro Leu Tyr Thr Pro Ser Ser Ser Phe 3185 3190 3195 3200 Gly Val Ser Ser Cys Leu Gly Gly Pro Leu Glu Lys Gly Ile Tyr Phe 3205 3210 3215 Ser Glu Glu Gly Gly His Val Val Leu Ala His Ser Val Leu Leu Gly 3220 3225 3230 Pro Glu Phe Lys Leu Val Phe Ser Ile Arg Pro Arg Ser Leu Thr Gly 3235 3240 3245 Ile Leu Ile His Ile Gly Ser Gln Pro Gly Lys His Leu Cys Val Tyr 3250 3255 3260 Leu Glu Ala Gly Lys Val Thr Ala Ser Met Asp Ser Gly Ala Gly Gly 3265 3270 3275 3280 Thr Ser Thr Ser Val Thr Pro Lys Gln Ser Leu Cys Asp Gly Gln Trp 3285 3290 3295 His Ser Val Ala Val Thr Ile Lys Gln His Ile Leu His Leu Glu Leu 3300 3305 3310 Asp Thr Asp Ser Ser Tyr Thr Ala Gly Gln Ile Pro Phe Pro Pro Ala 3315 3320 3325 Ser Thr Gln Glu Pro Leu His Leu Gly Gly Ala Pro Ala Asn Leu Thr 3330 3335 3340 Thr Leu Arg Ile Pro Val Trp Lys Ser Phe Phe Gly Cys Leu Arg Asn 3345 3350 3355 3360 Ile His Val Asn His Ile Pro Val Pro Val Thr Glu Ala Leu Glu Val 3365 3370 3375 Gln Gly Pro Val Ser Leu Asn Gly Cys Pro Asp Gln 3380 3385 <210> 11 <211> 357 <212> PRT <213> Homo sapiens <400> 11 Met Gly Arg Gln Leu Ala Gly Cys Gly Asp Ala Gly Lys Lys Ala Ser 1 5 10 15 Phe Lys Met Ser Thr Val His Glu Ile Leu Cys Lys Leu Ser Leu Glu 20 25 30 Gly Asp His Ser Thr Pro Pro Ser Ala Tyr Gly Ser Val Lys Ala Tyr 35 40 45 Thr Asn Phe Asp Ala Glu Arg Asp Ala Leu Asn Ile Glu Thr Ala Ile 50 55 60 Lys Thr Lys Gly Val Asp Glu Val Thr Ile Val Asn Ile Leu Thr Asn 65 70 75 80 Arg Ser Asn Ala Gln Arg Gln Asp Ile Ala Phe Ala Tyr Gln Arg Arg 85 90 95 Thr Lys Lys Glu Leu Ala Ser Ala Leu Lys Ser Ala Leu Ser Gly His 100 105 110 Leu Glu Thr Val Ile Leu Gly Leu Leu Lys Thr Pro Ala Gln Tyr Asp 115 120 125 Ala Ser Glu Leu Lys Ala Ser Met Lys Gly Leu Gly Thr Asp Glu Asp 130 135 140 Ser Leu Ile Glu Ile Ile Cys Ser Arg Thr Asn Gln Glu Leu Gln Glu 145 150 155 160 Ile Asn Arg Val Tyr Lys Glu Met Tyr Lys Thr Asp Leu Glu Lys Asp 165 170 175 Ile Ile Ser Asp Thr Ser Gly Asp Phe Arg Lys Leu Met Val Ala Leu 180 185 190 Ala Lys Gly Arg Arg Ala Glu Asp Gly Ser Val Ile Asp Tyr Glu Leu 195 200 205 Ile Asp Gln Asp Ala Arg Asp Leu Tyr Asp Ala Gly Val Lys Arg Lys 210 215 220 Gly Thr Asp Val Pro Lys Trp Ile Ser Ile Met Thr Glu Arg Ser Val 225 230 235 240 Pro His Leu Gln Lys Val Phe Asp Arg Tyr Lys Ser Tyr Ser Pro Tyr 245 250 255 Asp Met Leu Glu Ser Ile Arg Lys Glu Val Lys Gly Asp Leu Glu Asn 260 265 270 Ala Phe Leu Asn Leu Val Gln Cys Ile Gln Asn Lys Pro Leu Tyr Phe 275 280 285 Ala Asp Arg Leu Tyr Asp Ser Met Lys Gly Lys Gly Thr Arg Asp Lys 290 295 300 Val Leu Ile Arg Ile Met Val Ser Arg Ser Glu Val Asp Met Leu Lys 305 310 315 320 Ile Arg Ser Glu Phe Lys Arg Lys Tyr Gly Lys Ser Leu Tyr Tyr Tyr 325 330 335 Ile Gln Gln Asp Thr Lys Gly Asp Tyr Gln Lys Ala Leu Leu Tyr Leu 340 345 350 Cys Gly Gly Asp Asp 355 <210> 12 <211> 556 <212> PRT <213> Homo sapiens <400> 12 Met Glu Leu Cys Gly Leu Gly Leu Pro Arg Pro Pro Met Leu Leu Ala 1 5 10 15 Leu Leu Leu Ala Thr Leu Leu Ala Ala Met Leu Ala Leu Leu Thr Gln 20 25 30 Val Ala Leu Val Val Gln Val Ala Glu Ala Ala Arg Ala Pro Ser Val 35 40 45 Ser Ala Lys Pro Gly Pro Ala Leu Trp Pro Leu Pro Leu Ser Val Lys 50 55 60 Met Thr Pro Asn Leu Leu His Leu Ala Pro Glu Asn Phe Tyr Ile Ser 65 70 75 80 His Ser Pro Asn Ser Thr Ala Gly Pro Ser Cys Thr Leu Leu Glu Glu 85 90 95 Ala Phe Arg Arg Tyr His Gly Tyr Ile Phe Gly Phe Tyr Lys Trp His 100 105 110 His Glu Pro Ala Glu Phe Gln Ala Lys Thr Gln Val Gln Gln Leu Leu 115 120 125 Val Ser Ile Thr Leu Gln Ser Glu Cys Asp Ala Phe Pro Asn Ile Ser 130 135 140 Ser Asp Glu Ser Tyr Thr Leu Leu Val Lys Glu Pro Val Ala Val Leu 145 150 155 160 Lys Ala Asn Arg Val Trp Gly Ala Leu Arg Gly Leu Glu Thr Phe Ser 165 170 175 Gln Leu Val Tyr Gln Asp Ser Tyr Gly Thr Phe Thr Ile Asn Glu Ser 180 185 190 Thr Ile Ile Asp Ser Pro Arg Phe Ser His Arg Gly Ile Leu Ile Asp 195 200 205 Thr Ser Arg His Tyr Leu Pro Val Lys Ile Ile Leu Lys Thr Leu Asp 210 215 220 Ala Met Ala Phe Asn Lys Phe Asn Val Leu His Trp His Ile Val Asp 225 230 235 240 Asp Gln Ser Phe Pro Tyr Gln Ser Ile Thr Phe Pro Glu Leu Ser Asn 245 250 255 Lys Gly Ser Tyr Ser Leu Ser His Val Tyr Thr Pro Asn Asp Val Arg 260 265 270 Met Val Ile Glu Tyr Ala Arg Leu Arg Gly Ile Arg Val Leu Pro Glu 275 280 285 Phe Asp Thr Pro Gly His Thr Leu Ser Trp Gly Lys Gly Gln Lys Asp 290 295 300 Leu Leu Thr Pro Cys Tyr Ser Arg Gln Asn Lys Leu Asp Ser Phe Gly 305 310 315 320 Pro Ile Asn Pro Thr Leu Asn Thr Thr Tyr Ser Phe Leu Thr Thr Phe 325 330 335 Phe Lys Glu Ile Ser Glu Val Phe Pro Asp Gln Phe Ile His Leu Gly 340 345 350 Gly Asp Glu Val Glu Phe Lys Cys Trp Glu Ser Asn Pro Lys Ile Gln 355 360 365 Asp Phe Met Arg Gln Lys Gly Phe Gly Thr Asp Phe Lys Lys Leu Glu 370 375 380 Ser Phe Tyr Ile Gln Lys Val Leu Asp Ile Ile Ala Thr Ile Asn Lys 385 390 395 400 Gly Ser Ile Val Trp Gln Glu Val Phe Asp Asp Lys Ala Lys Leu Ala 405 410 415 Pro Gly Thr Ile Val Glu Val Trp Lys Asp Ser Ala Tyr Pro Glu Glu 420 425 430 Leu Ser Arg Val Thr Ala Ser Gly Phe Pro Val Ile Leu Ser Ala Pro 435 440 445 Trp Tyr Leu Asp Leu Ile Ser Tyr Gly Gln Asp Trp Arg Lys Tyr Tyr 450 455 460 Lys Val Glu Pro Leu Asp Phe Gly Gly Thr Gln Lys Gln Lys Gln Leu 465 470 475 480 Phe Ile Gly Gly Glu Ala Cys Leu Trp Gly Glu Tyr Val Asp Ala Thr 485 490 495 Asn Leu Thr Pro Arg Leu Trp Pro Arg Ala Ser Ala Val Gly Glu Arg 500 505 510 Leu Trp Ser Ser Lys Asp Val Arg Asp Met Asp Asp Ala Tyr Asp Arg 515 520 525 Leu Thr Arg His Arg Cys Arg Met Val Glu Arg Gly Ile Ala Ala Gln 530 535 540 Pro Leu Tyr Ala Gly Tyr Cys Asn His Glu Asn Met 545 550 555 <210> 13 <211> 368 <212> PRT <213> Homo sapiens <400> 13 Met Trp Pro Leu Trp Arg Leu Val Ser Leu Leu Ala Leu Ser Gln Ala 1 5 10 15 Leu Pro Phe Glu Gln Arg Gly Phe Trp Asp Phe Thr Leu Asp Asp Gly 20 25 30 Pro Phe Met Met Asn Asp Glu Glu Ala Ser Gly Ala Asp Thr Ser Gly 35 40 45 Val Leu Asp Pro Asp Ser Val Thr Pro Thr Tyr Ser Ala Met Cys Pro 50 55 60 Phe Gly Cys His Cys His Leu Arg Val Val Gln Cys Ser Asp Leu Gly 65 70 75 80 Leu Lys Ser Val Pro Lys Glu Ile Ser Pro Asp Thr Thr Leu Leu Asp 85 90 95 Leu Gln Asn Asn Asp Ile Ser Glu Leu Arg Lys Asp Asp Phe Lys Gly 100 105 110 Leu Gln His Leu Tyr Ala Leu Val Leu Val Asn Asn Lys Ile Ser Lys 115 120 125 Ile His Glu Lys Ala Phe Ser Pro Leu Arg Lys Leu Gln Lys Leu Tyr 130 135 140 Ile Ser Lys Asn His Leu Val Glu Ile Pro Pro Asn Leu Pro Ser Ser 145 150 155 160 Leu Val Glu Leu Arg Ile His Asp Asn Arg Ile Arg Lys Val Pro Lys 165 170 175 Gly Val Phe Ser Gly Leu Arg Asn Met Asn Cys Ile Glu Met Gly Gly 180 185 190 Asn Pro Leu Glu Asn Ser Gly Phe Glu Pro Gly Ala Phe Asp Gly Leu 195 200 205 Lys Leu Asn Tyr Leu Arg Ile Ser Glu Ala Lys Leu Thr Gly Ile Pro 210 215 220 Lys Asp Leu Pro Glu Thr Leu Asn Glu Leu His Leu Asp His Asn Lys 225 230 235 240 Ile Gln Ala Ile Glu Leu Glu Asp Leu Leu Arg Tyr Ser Lys Leu Tyr 245 250 255 Arg Leu Gly Leu Gly His Asn Gln Ile Arg Met Ile Glu Asn Gly Ser 260 265 270 Leu Ser Phe Leu Pro Thr Leu Arg Glu Leu His Leu Asp Asn Asn Lys 275 280 285 Leu Ala Arg Val Pro Ser Gly Leu Pro Asp Leu Lys Leu Leu Gln Val 290 295 300 Val Tyr Leu His Ser Asn Asn Ile Thr Lys Val Gly Val Asn Asp Phe 305 310 315 320 Cys Pro Met Gly Phe Gly Val Lys Arg Ala Tyr Tyr Asn Gly Ile Ser 325 330 335 Leu Phe Asn Asn Pro Val Pro Tyr Trp Glu Val Gln Pro Ala Thr Phe 340 345 350 Arg Cys Val Thr Asp Arg Leu Ala Ile Gln Phe Gly Asn Tyr Lys Lys 355 360 365 <210> 14 <211> 536 <212> PRT <213> Homo sapiens <400> 14 Met Glu Leu Ser Pro Arg Ser Pro Pro Glu Met Leu Glu Glu Ser Asp 1 5 10 15 Cys Pro Ser Pro Leu Glu Leu Lys Ser Ala Pro Ser Lys Lys Met Trp 20 25 30 Ile Lys Leu Arg Ser Leu Leu Arg Tyr Met Val Lys Gln Leu Glu Asn 35 40 45 Gly Glu Ile Asn Ile Glu Glu Leu Lys Lys Asn Leu Glu Tyr Thr Ala 50 55 60 Ser Leu Leu Glu Ala Val Tyr Ile Asp Glu Thr Arg Gln Ile Leu Asp 65 70 75 80 Thr Glu Asp Glu Leu Gln Glu Leu Arg Ser Asp Ala Val Pro Ser Glu 85 90 95 Val Arg Asp Trp Leu Ala Ser Thr Phe Thr Gln Gln Ala Arg Ala Lys 100 105 110 Gly Arg Arg Ala Glu Glu Lys Pro Lys Phe Arg Ser Ile Val His Ala 115 120 125 Val Gln Ala Gly Ile Phe Val Glu Arg Met Phe Arg Arg Thr Tyr Thr 130 135 140 Ser Val Gly Pro Thr Tyr Ser Thr Ala Val Leu Asn Cys Leu Lys Asn 145 150 155 160 Leu Asp Leu Trp Cys Phe Asp Val Phe Ser Leu Asn Gln Ala Ala Asp 165 170 175 Asp His Ala Leu Arg Thr Ile Val Phe Glu Leu Leu Thr Arg His Asn 180 185 190 Leu Ile Ser Arg Phe Lys Ile Pro Thr Val Phe Leu Met Ser Phe Leu 195 200 205 Asp Ala Leu Glu Thr Gly Tyr Gly Lys Tyr Lys Asn Pro Tyr His Asn 210 215 220 Gln Ile His Ala Ala Asp Val Thr Gln Thr Val His Cys Phe Leu Leu 225 230 235 240 Arg Thr Gly Met Val His Cys Leu Ser Glu Ile Glu Leu Leu Ala Ile 245 250 255 Ile Phe Ala Ala Ala Ile His Asp Tyr Glu His Thr Gly Thr Thr Asn 260 265 270 Ser Phe His Ile Gln Thr Lys Ser Glu Cys Ala Ile Val Tyr Asn Asp 275 280 285 Arg Ser Val Leu Glu Asn His His Ile Ser Ser Val Phe Arg Leu Met 290 295 300 Gln Asp Asp Glu Met Asn Ile Phe Ile Asn Leu Thr Lys Asp Glu Phe 305 310 315 320 Val Glu Leu Arg Ala Leu Val Ile Glu Met Val Leu Ala Thr Asp Met 325 330 335 Ser Cys His Phe Gln Gln Val Lys Thr Met Lys Thr Ala Leu Gln Gln 340 345 350 Leu Glu Arg Ile Asp Lys Pro Lys Ala Leu Ser Leu Leu Leu His Ala 355 360 365 Ala Asp Ile Ser His Pro Thr Lys Gln Trp Leu Val His Ser Arg Trp 370 375 380 Thr Lys Ala Leu Met Glu Glu Phe Phe Arg Gln Gly Asp Lys Glu Ala 385 390 395 400 Glu Leu Gly Leu Pro Phe Ser Pro Leu Cys Asp Arg Thr Ser Thr Leu 405 410 415 Val Ala Gln Ser Gln Ile Gly Phe Ile Asp Phe Ile Val Glu Pro Thr 420 425 430 Phe Ser Val Leu Thr Asp Val Ala Glu Lys Ser Val Gln Pro Leu Ala 435 440 445 Asp Glu Asp Ser Lys Ser Lys Asn Gln Pro Ser Phe Gln Trp Arg Gln 450 455 460 Pro Ser Leu Asp Val Glu Val Gly Asp Pro Asn Pro Asp Val Val Ser 465 470 475 480 Phe Arg Ser Thr Trp Val Lys Arg Ile Gln Glu Asn Lys Gln Lys Trp 485 490 495 Lys Glu Arg Ala Ala Ser Gly Ile Thr Asn Gln Met Ser Ile Asp Glu 500 505 510 Leu Ser Pro Cys Glu Glu Glu Ala Pro Pro Ser Pro Ala Glu Asp Glu 515 520 525 His Asn Gln Asn Gly Asn Leu Asp 530 535 <210> 15 <211> 146 <212> PRT <213> Homo sapiens <400> 15 Met Ala Gly Glu Leu Thr Pro Glu Glu Glu Ala Gln Tyr Lys Lys Ala 1 5 10 15 Phe Ser Ala Val Asp Thr Asp Gly Asn Gly Thr Ile Asn Ala Gln Glu 20 25 30 Leu Gly Ala Ala Leu Lys Ala Thr Gly Lys Asn Leu Ser Glu Ala Gln 35 40 45 Leu Arg Lys Leu Ile Ser Glu Val Asp Ser Asp Gly Asp Gly Glu Ile 50 55 60 Ser Phe Gln Glu Phe Leu Thr Ala Ala Arg Lys Ala Arg Ala Gly Leu 65 70 75 80 Glu Asp Leu Gln Val Ala Phe Arg Ala Phe Asp Gln Asp Gly Asp Gly 85 90 95 His Ile Thr Val Asp Glu Leu Arg Arg Ala Met Ala Gly Leu Gly Gln 100 105 110 Pro Leu Pro Gln Glu Glu Leu Asp Ala Met Ile Arg Glu Ala Asp Val 115 120 125 Asp Gln Asp Gly Arg Val Asn Tyr Glu Glu Phe Ala Arg Met Leu Ala 130 135 140 Gln Glu 145 <210> 16 <211> 128 <212> PRT <213> Homo sapiens <400> 16 Met Gly Ile Gln Gly Gly Ser Val Leu Phe Gly Leu Leu Leu Val Leu 1 5 10 15 Ala Val Phe Cys His Ser Gly His Ser Leu Gln Cys Tyr Asn Cys Pro 20 25 30 Asn Pro Thr Ala Asp Cys Lys Thr Ala Val Asn Cys Ser Ser Asp Phe 35 40 45 Asp Ala Cys Leu Ile Thr Lys Ala Gly Leu Gln Val Tyr Asn Lys Cys 50 55 60 Trp Lys Phe Glu His Cys Asn Phe Asn Asp Val Thr Thr Arg Leu Arg 65 70 75 80 Glu Asn Glu Leu Thr Tyr Tyr Cys Cys Lys Lys Asp Leu Cys Asn Phe 85 90 95 Asn Glu Gln Leu Glu Asn Gly Gly Thr Ser Leu Ser Glu Lys Thr Val 100 105 110 Leu Leu Leu Val Thr Pro Phe Leu Ala Ala Ala Trp Ser Leu His Pro 115 120 125 <210> 17 <211> 293 <212> PRT <213> Homo sapiens <400> 17 Met Glu Asn Gly Tyr Thr Tyr Glu Asp Tyr Lys Asn Thr Ala Glu Trp 1 5 10 15 Leu Leu Ser His Thr Lys His Arg Pro Gln Val Ala Ile Ile Cys Gly 20 25 30 Ser Gly Leu Gly Gly Leu Thr Asp Lys Leu Thr Gln Ala Gln Ile Phe 35 40 45 Asp Tyr Gly Glu Ile Pro Asn Phe Pro Arg Ser Thr Val Pro Gly His 50 55 60 Ala Gly Arg Leu Val Phe Gly Phe Leu Asn Gly Arg Ala Cys Val Met 65 70 75 80 Met Gln Gly Arg Phe His Met Tyr Glu Gly Tyr Pro Leu Trp Lys Phe 85 90 95 Ala Ser Lys Val Thr Phe Pro Val Arg Val Phe His Leu Leu Gly Val 100 105 110 Asp Thr Leu Val Val Thr Asn Ala Ala Gly Gly Leu Asn Pro Lys Phe 115 120 125 Glu Val Gly Asp Ile Met Leu Ile Arg Asp His Ile Asn Leu Pro Gly 130 135 140 Phe Ser Gly Gln Asn Pro Leu Arg Gly Pro Asn Asp Glu Arg Phe Gly 145 150 155 160 Asp Arg Phe Pro Ala Met Ser Asp Ala Tyr Asp Arg Thr Met Arg Gln 165 170 175 Arg Ala Leu Ser Thr Trp Lys Gln Met Gly Glu Gln Arg Glu Leu Gln 180 185 190 Glu Gly Thr Tyr Val Met Val Ala Gly Pro Ser Phe Glu Thr Val Ala 195 200 205 Glu Cys Arg Val Leu Gln Lys Leu Gly Ala Asp Ala Val Gly Met Ser 210 215 220 Thr Val Pro Glu Val Ile Val Ala Arg His Cys Gly Leu Arg Val Phe 225 230 235 240 Gly Phe Ser Leu Ile Thr Asn Lys Val Ile Met Asp Tyr Glu Ser Leu 245 250 255 Glu Lys Ala Asn His Glu Glu Val Leu Ala Ala Gly Lys Gln Ala Ala 260 265 270 Gln Lys Leu Glu Gln Phe Val Ser Ile Leu Met Ala Ser Ile Pro Leu 275 280 285 Pro Asp Lys Ala Ser 290 <210> 18 <211> 487 <212> PRT <213> Homo sapiens <400> 18 Met Glu Leu Gly Leu Ser Trp Val Phe Leu Val Ala Ile Leu Glu Gly 1 5 10 15 Val His Cys Glu Ala Gln Val Val Glu Ser Gly Gly Gly Leu Val Gln 20 25 30 Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Pro Phe 35 40 45 Ser Ser Phe Trp Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 50 55 60 Glu Trp Val Ala Ser Ile Asn Lys Asp Gly Arg Asp Ser Tyr Tyr Val 65 70 75 80 Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Glu Thr 85 90 95 Ser Leu Tyr Leu Gln Met Gly Ser Leu Arg Ala Glu Asp Thr Ala Val 100 105 110 Tyr Tyr Cys Ala Arg Lys Phe Met Phe Asp Ser Trp Ser Ser Tyr Tyr 115 120 125 Val Glu Gly His Tyr Phe Asp Leu Trp Gly Arg Gly Thr Gln Val Thr 130 135 140 Val Ser Ser Ala Ser Pro Thr Ser Pro Lys Val Phe Pro Leu Ser Leu 145 150 155 160 Asp Ser Thr Pro Gln Asp Gly Asn Val Val Val Ala Cys Leu Val Gln 165 170 175 Gly Phe Phe Pro Gln Glu Pro Leu Ser Val Thr Trp Ser Glu Ser Gly 180 185 190 Gln Asn Val Thr Ala Arg Asn Phe Pro Pro Ser Gln Asp Ala Ser Gly 195 200 205 Asp Leu Tyr Thr Thr Ser Ser Gln Leu Thr Leu Pro Ala Thr Gln Cys 210 215 220 Pro Asp Gly Lys Ser Val Thr Cys His Val Lys His Tyr Thr Asn Pro 225 230 235 240 Ser Gln Asp Val Thr Val Pro Cys Pro Val Pro Pro Pro Pro Pro Cys 245 250 255 Cys His Pro Arg Leu Ser Leu His Arg Pro Ala Leu Glu Asp Leu Leu 260 265 270 Leu Gly Ser Glu Ala Asn Leu Thr Cys Thr Leu Thr Gly Leu Arg Asp 275 280 285 Ala Ser Gly Ala Thr Phe Thr Trp Thr Pro Ser Ser Gly Lys Ser Ala 290 295 300 Val Gln Gly Pro Pro Glu Arg Asp Leu Cys Gly Cys Tyr Ser Val Ser 305 310 315 320 Ser Val Leu Pro Gly Cys Ala Gln Pro Trp Asn His Gly Glu Thr Phe 325 330 335 Thr Cys Thr Ala Ala His Pro Glu Leu Lys Thr Pro Leu Thr Ala Asn 340 345 350 Ile Thr Lys Ser Gly Asn Thr Phe Arg Pro Glu Val His Leu Leu Pro 355 360 365 Pro Pro Ser Glu Glu Leu Ala Leu Asn Glu Leu Val Thr Leu Thr Cys 370 375 380 Leu Ala Arg Gly Phe Ser Pro Lys Asp Val Leu Val Arg Trp Leu Gln 385 390 395 400 Gly Ser Gln Glu Leu Pro Arg Glu Lys Tyr Leu Thr Trp Ala Ser Arg 405 410 415 Gln Glu Pro Ser Gln Gly Thr Thr Thr Phe Ala Val Thr Ser Ile Leu 420 425 430 Arg Val Ala Ala Glu Asp Trp Lys Lys Gly Asp Thr Phe Ser Cys Met 435 440 445 Val Gly His Glu Ala Leu Pro Leu Ala Phe Thr Gln Lys Thr Ile Asp 450 455 460 Arg Leu Ala Gly Lys Pro Thr His Val Asn Val Ser Val Val Met Ala 465 470 475 480 Glu Val Asp Gly Thr Cys Tyr 485 <210> 19 <211> 643 <212> PRT <213> Homo sapiens <400> 19 Met Ser Val Gln Ser Asn Leu Gln Ala Gly Ala Ala Ala Ala Ser Cys 1 5 10 15 Ile Ser Pro Lys Tyr Tyr Met Ile Phe Thr Pro Cys Lys Leu Cys His 20 25 30 Leu Cys Cys Arg Glu Ser Glu Ile Asn Met His Ser Lys Val Thr Ile 35 40 45 Ile Cys Ile Arg Phe Leu Phe Trp Phe Leu Leu Leu Cys Met Leu Ile 50 55 60 Gly Lys Ser His Thr Glu Asp Asp Ile Ile Ile Ala Thr Lys Asn Gly 65 70 75 80 Lys Val Arg Gly Met Asn Leu Thr Val Phe Gly Gly Thr Val Thr Ala 85 90 95 Phe Leu Gly Ile Pro Tyr Ala Gln Pro Pro Leu Gly Arg Leu Arg Phe 100 105 110 Lys Lys Pro Gln Ser Leu Thr Lys Trp Ser Asp Ile Trp Asn Ala Thr 115 120 125 Lys Tyr Ala Asn Ser Cys Cys Gln Asn Ile Asp Gln Ser Phe Pro Gly 130 135 140 Phe His Gly Ser Glu Met Trp Asn Pro Asn Thr Asp Leu Ser Glu Asp 145 150 155 160 Cys Leu Tyr Leu Asn Val Trp Ile Pro Ala Pro Lys Pro Lys Asn Ala 165 170 175 Thr Val Leu Ile Trp Ile Tyr Gly Gly Gly Phe Gln Thr Gly Thr Ser 180 185 190 Ser Leu His Val Tyr Asp Gly Lys Phe Leu Ala Arg Val Glu Arg Val 195 200 205 Ile Val Val Ser Met Asn Tyr Arg Val Gly Ala Leu Gly Phe Leu Ala 210 215 220 Leu Pro Gly Asn Pro Glu Ala Pro Gly Asn Met Gly Leu Phe Asp Gln 225 230 235 240 Gln Leu Ala Leu Gln Trp Val Gln Lys Asn Ile Ala Ala Phe Gly Gly 245 250 255 Asn Pro Lys Ser Val Thr Leu Phe Gly Glu Ser Ala Gly Ala Ala Ser 260 265 270 Val Ser Leu His Leu Leu Ser Pro Gly Ser His Ser Leu Phe Thr Arg 275 280 285 Ala Ile Leu Gln Ser Gly Ser Phe Asn Ala Pro Trp Ala Val Thr Ser 290 295 300 Leu Tyr Glu Ala Arg Asn Arg Thr Leu Asn Leu Ala Lys Leu Thr Gly 305 310 315 320 Cys Ser Arg Glu Asn Glu Thr Glu Ile Ile Lys Cys Leu Arg Asn Lys 325 330 335 Asp Pro Gln Glu Ile Leu Leu Asn Glu Ala Phe Val Val Pro Tyr Gly 340 345 350 Thr Pro Leu Ser Val Asn Phe Gly Pro Thr Val Asp Gly Asp Phe Leu 355 360 365 Thr Asp Met Pro Asp Ile Leu Leu Glu Leu Gly Gln Phe Lys Lys Thr 370 375 380 Gln Ile Leu Val Gly Val Asn Lys Asp Glu Gly Thr Ala Phe Leu Val 385 390 395 400 Tyr Gly Ala Pro Gly Phe Ser Lys Asp Asn Asn Ser Ile Ile Thr Arg 405 410 415 Lys Glu Phe Gln Glu Gly Leu Lys Ile Phe Phe Pro Gly Val Ser Glu 420 425 430 Phe Gly Lys Glu Ser Ile Leu Phe His Tyr Thr Asp Trp Val Asp Asp 435 440 445 Gln Arg Pro Glu Asn Tyr Arg Glu Ala Leu Gly Asp Val Val Gly Asp 450 455 460 Tyr Asn Phe Ile Cys Pro Ala Leu Glu Phe Thr Lys Lys Phe Ser Glu 465 470 475 480 Trp Gly Asn Asn Ala Phe Phe Tyr Tyr Phe Glu His Arg Ser Ser Lys 485 490 495 Leu Pro Trp Pro Glu Trp Met Gly Val Met His Gly Tyr Glu Ile Glu 500 505 510 Phe Val Phe Gly Leu Pro Leu Glu Arg Arg Asp Asn Tyr Thr Lys Ala 515 520 525 Glu Glu Ile Leu Ser Arg Ser Ile Val Lys Arg Trp Ala Asn Phe Ala 530 535 540 Lys Tyr Gly Asn Pro Asn Glu Thr Gln Asn Asn Ser Thr Ser Trp Pro 545 550 555 560 Val Phe Lys Ser Thr Glu Gln Lys Tyr Leu Thr Leu Asn Thr Glu Ser 565 570 575 Thr Arg Ile Met Thr Lys Leu Arg Ala Gln Gln Cys Arg Phe Trp Thr 580 585 590 Ser Phe Phe Pro Lys Val Leu Glu Met Thr Gly Asn Ile Asp Glu Ala 595 600 605 Glu Trp Glu Trp Lys Ala Gly Phe His Arg Trp Asn Asn Tyr Met Met 610 615 620 Asp Trp Lys Asn Gln Phe Asn Asp Tyr Thr Ser Lys Lys Glu Ser Cys 625 630 635 640 Val Gly Leu <210> 20 <211> 165 <212> PRT <213> Homo sapiens <400> 20 Ala Ser Gly Val Ala Val Ser Asp Gly Val Ile Lys Val Phe Asn Asp 1 5 10 15 Met Lys Val Arg Lys Ser Ser Thr Pro Glu Glu Val Lys Lys Arg Lys 20 25 30 Lys Ala Val Leu Phe Cys Leu Ser Glu Asp Lys Lys Asn Ile Ile Leu 35 40 45 Glu Glu Gly Lys Glu Ile Leu Val Gly Asp Val Gly Gln Thr Val Asp 50 55 60 Asp Pro Tyr Ala Thr Phe Val Lys Met Leu Pro Asp Lys Asp Cys Arg 65 70 75 80 Tyr Ala Leu Tyr Asp Ala Thr Tyr Glu Thr Lys Glu Ser Lys Lys Glu 85 90 95 Asp Leu Val Phe Ile Phe Trp Ala Pro Glu Ser Ala Pro Leu Lys Ser 100 105 110 Lys Met Ile Tyr Ala Ser Ser Lys Asp Ala Ile Lys Lys Lys Leu Thr 115 120 125 Gly Ile Lys His Glu Leu Gln Ala Asn Cys Tyr Glu Glu Val Lys Asp 130 135 140 Arg Cys Thr Leu Ala Glu Lys Leu Gly Gly Ser Ala Val Ile Ser Leu 145 150 155 160 Glu Gly Lys Pro Leu 165 <210> 21 <211> 529 <212> PRT <213> Homo sapiens <400> 21 Met Gly Ser Ser Arg Ala Pro Trp Met Gly Arg Val Gly Gly His Gly 1 5 10 15 Met Met Ala Leu Leu Leu Ala Gly Leu Leu Leu Pro Gly Thr Leu Ala 20 25 30 Lys Ser Ile Gly Thr Phe Ser Asp Pro Cys Lys Asp Pro Thr Arg Ile 35 40 45 Thr Ser Pro Asn Asp Pro Cys Leu Thr Gly Lys Gly Asp Ser Ser Gly 50 55 60 Phe Ser Ser Tyr Ser Gly Ser Ser Ser Ser Gly Ser Ser Ile Ser Ser 65 70 75 80 Ala Arg Ser Ser Gly Gly Gly Ser Ser Gly Ser Ser Ser Gly Ser Ser 85 90 95 Ile Ala Gln Gly Gly Ser Ala Gly Ser Phe Lys Pro Gly Thr Gly Tyr 100 105 110 Ser Gln Val Ser Tyr Ser Ser Gly Ser Gly Ser Ser Leu Gln Gly Ala 115 120 125 Ser Gly Ser Ser Gln Leu Gly Ser Ser Ser Ser His Ser Gly Ser Ser 130 135 140 Gly Ser His Ser Gly Ser Ser Ser Ser His Ser Ser Ser Ser Ser Ser 145 150 155 160 Phe Gln Phe Ser Ser Ser Ser Phe Gln Val Gly Asn Gly Ser Ala Leu 165 170 175 Pro Thr Asn Asp Asn Ser Tyr Arg Gly Ile Leu Asn Pro Ser Gln Pro 180 185 190 Gly Gln Ser Ser Ser Ser Ser Gln Thr Ser Gly Val Ser Ser Ser Gly 195 200 205 Gln Ser Val Ser Ser Asn Gln Arg Pro Cys Ser Ser Asp Ile Pro Asp 210 215 220 Ser Pro Cys Ser Gly Gly Pro Ile Val Ser His Ser Gly Pro Tyr Ile 225 230 235 240 Pro Ser Ser His Ser Val Ser Gly Gly Gln Arg Pro Val Val Val Val 245 250 255 Val Asp Gln His Gly Ser Gly Ala Pro Gly Val Val Gln Gly Pro Pro 260 265 270 Cys Ser Asn Gly Gly Leu Pro Gly Lys Pro Cys Pro Pro Ile Thr Ser 275 280 285 Val Asp Lys Ser Tyr Gly Gly Tyr Glu Val Val Gly Gly Ser Ser Asp 290 295 300 Ser Tyr Leu Val Pro Gly Met Thr Tyr Ser Lys Gly Lys Ile Tyr Pro 305 310 315 320 Val Gly Tyr Phe Thr Lys Glu Asn Pro Val Lys Gly Ser Pro Gly Val 325 330 335 Pro Ser Phe Ala Ala Gly Pro Pro Ile Ser Glu Gly Lys Tyr Phe Ser 340 345 350 Ser Asn Pro Ile Ile Pro Ser Gln Ser Ala Ala Ser Ser Ala Ile Ala 355 360 365 Phe Gln Pro Val Gly Thr Gly Gly Val Gln Leu Cys Gly Gly Gly Ser 370 375 380 Thr Gly Ser Lys Gly Pro Cys Ser Pro Ser Ser Ser Arg Val Pro Ser 385 390 395 400 Ser Ser Ser Ile Ser Ser Ser Ser Gly Ser Pro Tyr His Pro Cys Gly 405 410 415 Ser Ala Ser Gln Ser Pro Cys Ser Pro Pro Gly Thr Gly Ser Phe Ser 420 425 430 Ser Ser Ser Ser Ser Gln Ser Ser Gly Lys Ile Ile Leu Gln Pro Cys 435 440 445 Gly Ser Lys Ser Ser Ser Ser Gly His Pro Cys Met Ser Val Ser Ser 450 455 460 Leu Thr Leu Thr Gly Gly Pro Asp Gly Ser Pro His Pro Asp Pro Ser 465 470 475 480 Ala Gly Ala Lys Pro Cys Gly Ser Ser Ser Ala Gly Lys Ile Pro Cys 485 490 495 Arg Ser Ile Arg Asp Ile Leu Ala Gln Val Lys Pro Leu Gly Pro Gln 500 505 510 Leu Ala Asp Pro Glu Val Phe Leu Pro Gln Gly Glu Leu Leu Asp Ser 515 520 525 Pro <210> 22 <211> 201 <212> PRT <213> Homo sapiens <400> 22 Met Asp Leu Ser Leu Leu Trp Val Leu Leu Pro Leu Val Thr Met Ala 1 5 10 15 Trp Gly Gln Tyr Gly Asp Tyr Gly Tyr Pro Tyr Gln Gln Tyr His Asp 20 25 30 Tyr Ser Asp Asp Gly Trp Val Asn Leu Asn Arg Gln Gly Phe Ser Tyr 35 40 45 Gln Cys Pro Gln Gly Gln Val Ile Val Ala Val Arg Ser Ile Phe Ser 50 55 60 Lys Lys Glu Gly Ser Asp Arg Gln Trp Asn Tyr Ala Cys Met Pro Thr 65 70 75 80 Pro Gln Ser Leu Gly Glu Pro Thr Glu Cys Trp Trp Glu Glu Ile Asn 85 90 95 Arg Ala Gly Met Glu Trp Tyr Gln Thr Cys Ser Asn Asn Gly Leu Val 100 105 110 Ala Gly Phe Gln Ser Arg Tyr Phe Glu Ser Val Leu Asp Arg Glu Trp 115 120 125 Gln Phe Tyr Cys Cys Arg Tyr Ser Lys Arg Cys Pro Tyr Ser Cys Trp 130 135 140 Leu Thr Thr Glu Tyr Pro Gly His Tyr Gly Glu Glu Met Asp Met Ile 145 150 155 160 Ser Tyr Asn Tyr Asp Tyr Tyr Ile Arg Gly Ala Thr Thr Thr Phe Ser 165 170 175 Ala Val Glu Arg Asp Arg Gln Trp Lys Phe Ile Met Cys Arg Met Thr 180 185 190 Glu Tyr Asp Cys Glu Phe Ala Asn Val 195 200 <210> 23 <211> 2612 <212> PRT <213> Homo sapiens <400> 23 Met Ala Asp Val Asp Pro Asp Thr Leu Leu Glu Trp Leu Gln Met Gly 1 5 10 15 Gln Gly Asp Glu Arg Asp Met Gln Leu Ile Ala Leu Glu Gln Leu Cys 20 25 30 Met Leu Leu Leu Met Ser Asp Asn Val Asp Arg Cys Phe Glu Thr Cys 35 40 45 Pro Pro Arg Thr Phe Leu Pro Ala Leu Cys Lys Ile Phe Leu Asp Glu 50 55 60 Ser Ala Pro Asp Asn Val Leu Glu Val Thr Ala Arg Ala Ile Thr Tyr 65 70 75 80 Tyr Leu Asp Val Ser Ala Glu Cys Thr Arg Arg Ile Val Gly Val Asp 85 90 95 Gly Ala Ile Lys Ala Leu Cys Asn Arg Leu Val Val Val Glu Leu Asn 100 105 110 Asn Arg Thr Ser Arg Asp Leu Ala Glu Gln Cys Val Lys Val Leu Glu 115 120 125 Leu Ile Cys Thr Arg Glu Ser Gly Ala Val Phe Glu Ala Gly Gly Leu 130 135 140 Asn Cys Val Leu Thr Phe Ile Arg Asp Ser Gly His Leu Val His Lys 145 150 155 160 Asp Thr Leu His Ser Ala Met Ala Val Val Ser Arg Leu Cys Gly Lys 165 170 175 Met Glu Pro Gln Asp Ser Ser Leu Glu Ile Cys Val Glu Ser Leu Ser 180 185 190 Ser Leu Leu Lys His Glu Asp His Gln Val Ser Asp Gly Ala Leu Arg 195 200 205 Cys Phe Ala Ser Leu Ala Asp Arg Phe Thr Arg Arg Gly Val Asp Pro 210 215 220 Ala Pro Leu Ala Lys His Gly Leu Thr Glu Glu Leu Leu Ser Arg Met 225 230 235 240 Ala Ala Ala Gly Gly Thr Val Ser Gly Pro Ser Ser Ala Cys Lys Pro 245 250 255 Gly Arg Ser Thr Thr Gly Ala Pro Ser Thr Thr Ala Asp Ser Lys Leu 260 265 270 Ser Asn Gln Val Ser Thr Ile Val Ser Leu Leu Ser Thr Leu Cys Arg 275 280 285 Gly Ser Pro Val Val Thr His Asp Leu Leu Arg Ser Glu Leu Pro Asp 290 295 300 Ser Ile Glu Ser Ala Leu Gln Gly Asp Glu Arg Cys Val Leu Asp Thr 305 310 315 320 Met Arg Leu Val Asp Leu Leu Leu Val Leu Leu Phe Glu Gly Arg Lys 325 330 335 Ala Leu Pro Lys Ser Ser Ala Gly Ser Thr Gly Arg Ile Pro Gly Leu 340 345 350 Arg Arg Leu Asp Ser Ser Gly Glu Arg Ser His Arg Gln Leu Ile Asp 355 360 365 Cys Ile Arg Ser Lys Asp Thr Asp Ala Leu Ile Asp Ala Ile Asp Thr 370 375 380 Gly Ala Phe Glu Val Asn Phe Met Asp Asp Val Gly Gln Thr Leu Leu 385 390 395 400 Asn Trp Ala Ser Ala Phe Gly Thr Gln Glu Met Val Glu Phe Leu Cys 405 410 415 Glu Arg Gly Ala Asp Val Asn Arg Gly Gln Arg Ser Ser Ser Leu His 420 425 430 Tyr Ala Ala Cys Phe Gly Arg Pro Gln Val Ala Lys Thr Leu Leu Arg 435 440 445 His Gly Ala Asn Pro Asp Leu Arg Asp Glu Asp Gly Lys Thr Pro Leu 450 455 460 Asp Lys Ala Arg Glu Arg Gly His Ser Glu Val Val Ala Ile Leu Gln 465 470 475 480 Ser Pro Gly Asp Trp Met Cys Pro Val Asn Lys Gly Asp Asp Lys Lys 485 490 495 Lys Lys Asp Thr Asn Lys Asp Glu Glu Glu Cys Asn Glu Pro Lys Gly 500 505 510 Asp Pro Glu Met Ala Pro Ile Tyr Leu Lys Arg Leu Leu Pro Val Phe 515 520 525 Ala Gln Thr Phe Gln Gln Thr Met Leu Pro Ser Ile Arg Lys Ala Ser 530 535 540 Leu Ala Leu Ile Arg Lys Met Ile His Phe Cys Ser Glu Ala Leu Leu 545 550 555 560 Gln Glu Val Cys Asp Ser Asp Val Gly His Asn Leu Pro Thr Ile Leu 565 570 575 Val Glu Ile Thr Ala Thr Val Leu Asp Gln Glu Asp Asp Asp Asp Gly 580 585 590 His Leu Leu Ala Leu Gln Ile Ile Arg Asp Ile Val Asp Lys Gly Gly 595 600 605 Asp Ile Tyr Lys His Gln Leu Ala Arg Leu Gly Val Ile Ser Lys Val 610 615 620 Ser Thr Leu Ala Gly Pro Ser Ser Asp Asp Glu Asn Glu Glu Glu Ser 625 630 635 640 Lys Pro Glu Lys Glu Asp Glu Pro Gln Glu Asp Ala Gln Glu Leu Gln 645 650 655 Gln Gly Lys Pro Tyr His Trp Arg Asp Trp Ser Ile Ile Arg Gly Arg 660 665 670 Asp Cys Leu Tyr Ile Trp Ser Asp Ala Ala Ala Leu Glu Leu Ser Asn 675 680 685 Gly Ser Asn Gly Trp Phe Arg Phe Ile Leu Asp Gly Lys Leu Ala Thr 690 695 700 Met Tyr Ser Ser Gly Ser Pro Glu Gly Gly Ser Asp Ser Ser Glu Ser 705 710 715 720 Arg Ser Glu Phe Leu Glu Lys Leu Gln Arg Ala Arg Gly Gln Val Lys 725 730 735 Pro Ser Thr Ser Ser Gln Pro Ile Leu Ser Ala Pro Gly Pro Thr Lys 740 745 750 Leu Thr Val Gly Asn Trp Ser Leu Thr Cys Leu Lys Glu Gly Glu Ile 755 760 765 Ala Ile His Asn Ser Asp Gly Gln Gln Ala Thr Ile Leu Lys Glu Asp 770 775 780 Leu Pro Gly Phe Val Phe Glu Ser Asn Arg Gly Thr Lys His Ser Phe 785 790 795 800 Thr Ala Glu Thr Ser Leu Gly Ser Glu Phe Val Thr Gly Trp Thr Gly 805 810 815 Lys Arg Gly Arg Lys Leu Lys Ser Lys Leu Glu Lys Thr Lys Gln Lys 820 825 830 Val Arg Thr Met Ala Arg Asp Leu Tyr Asp Asp His Phe Lys Ala Val 835 840 845 Glu Ser Met Pro Arg Gly Val Val Val Thr Leu Arg Asn Ile Ala Thr 850 855 860 Gln Leu Glu Ser Ser Trp Glu Leu His Thr Asn Arg Gln Cys Ile Glu 865 870 875 880 Ser Glu Asn Thr Trp Arg Asp Leu Met Lys Thr Ala Leu Lys Asn Leu 885 890 895 Ile Val Leu Leu Lys Asp Glu Asn Thr Ile Ser Pro Tyr Glu Met Cys 900 905 910 Ser Ser Gly Leu Val Gln Ala Leu Leu Thr Val Leu Asn Asn Val Ser 915 920 925 Ile Phe Arg Ala Thr Lys Gln Lys Gln Asn Glu Val Pro Lys Val Ile 930 935 940 Leu Ser Val Phe Lys Thr Ala Phe Thr Glu Asn Glu Asp Asp Glu Ser 945 950 955 960 Arg Pro Ala Val Ala Leu Ile Arg Lys Leu Ile Ala Val Leu Glu Ser 965 970 975 Ile Glu Arg Leu Pro Leu His Leu Tyr Asp Thr Pro Gly Ser Thr Tyr 980 985 990 Asn Leu Gln Ile Leu Thr Arg Arg Leu Arg Phe Arg Leu Glu Arg Ala 995 1000 1005 Pro Gly Glu Thr Ala Leu Ile Asp Arg Thr Gly Arg Met Leu Lys Met 1010 1015 1020 Glu Pro Leu Ala Thr Val Glu Ser Leu Glu Gln Tyr Leu Leu Lys Met 1025 1030 1035 1040 Val Ala Lys Gln Trp Tyr Asp Phe Asp Arg Ser Ser Phe Val Phe Val 1045 1050 1055 Arg Lys Leu Arg Glu Gly Gln Asn Phe Ile Phe Arg His Gln His Asp 1060 1065 1070 Phe Asp Glu Asn Gly Ile Ile Tyr Trp Ile Gly Thr Asn Ala Lys Thr 1075 1080 1085 Ala Tyr Glu Trp Val Asn Pro Ala Ala Tyr Gly Leu Val Val Val Thr 1090 1095 1100 Ser Ser Glu Gly Arg Asn Leu Pro Tyr Gly Arg Leu Glu Asp Ile Leu 1105 1110 1115 1120 Ser Arg Asp Asn Ser Ala Leu Asn Cys His Ser Asn Asp Asp Lys Asn 1125 1130 1135 Ala Trp Phe Ala Ile Asp Leu Gly Leu Trp Val Ile Pro Ser Ala Tyr 1140 1145 1150 Thr Leu Arg His Ala Arg Gly Tyr Gly Arg Ser Ala Leu Arg Asn Trp 1155 1160 1165 Val Phe Gln Val Ser Lys Asp Gly Gln Asn Trp Thr Ser Leu Tyr Thr 1170 1175 1180 His Val Asp Asp Cys Ser Leu Asn Glu Pro Gly Ser Thr Ala Thr Trp 1185 1190 1195 1200 Pro Leu Asp Pro Pro Lys Asp Glu Lys Gln Gly Trp Arg His Val Arg 1205 1210 1215 Ile Lys Gln Met Gly Lys Asn Ala Ser Gly Gln Thr His Tyr Leu Ser 1220 1225 1230 Leu Ser Gly Phe Glu Leu Tyr Gly Thr Val Asn Gly Val Cys Glu Asp 1235 1240 1245 Gln Leu Gly Lys Ala Ala Lys Glu Ala Glu Ala Asn Leu Arg Arg Gln 1250 1255 1260 Arg Arg Leu Val Arg Ser Gln Val Leu Lys Tyr Met Val Pro Gly Ala 1265 1270 1275 1280 Arg Val Ile Arg Gly Leu Asp Trp Lys Trp Arg Asp Gln Asp Gly Ser 1285 1290 1295 Pro Gln Gly Glu Gly Thr Val Thr Gly Glu Leu His Asn Gly Trp Ile 1300 1305 1310 Asp Val Thr Trp Asp Ala Gly Gly Ser Asn Ser Tyr Arg Met Gly Ala 1315 1320 1325 Glu Gly Lys Phe Asp Leu Lys Leu Ala Pro Gly Tyr Asp Pro Asp Thr 1330 1335 1340 Val Ala Ser Pro Lys Pro Val Ser Ser Thr Val Ser Gly Thr Thr Gln 1345 1350 1355 1360 Ser Trp Ser Ser Leu Val Lys Asn Asn Cys Pro Asp Lys Thr Ser Ala 1365 1370 1375 Ala Ala Gly Ser Ser Ser Arg Lys Gly Ser Ser Ser Ser Val Cys Ser 1380 1385 1390 Val Ala Ser Ser Ser Asp Ile Ser Leu Gly Ser Thr Lys Thr Glu Arg 1395 1400 1405 Arg Ser Glu Ile Val Met Glu His Ser Ile Val Ser Gly Ala Asp Val 1410 1415 1420 His Glu Pro Ile Val Val Leu Ser Ser Ala Glu Asn Val Pro Gln Thr 1425 1430 1435 1440 Glu Val Gly Ser Ser Ser Ser Ala Ser Thr Ser Thr Leu Thr Ala Glu 1445 1450 1455 Thr Gly Ser Glu Asn Ala Glu Arg Lys Leu Gly Pro Asp Ser Ser Val 1460 1465 1470 Arg Thr Pro Gly Glu Ser Ser Ala Ile Ser Met Gly Ile Val Ser Val 1475 1480 1485 Ser Ser Pro Asp Val Ser Ser Val Ser Glu Leu Thr Asn Lys Glu Ala 1490 1495 1500 Ala Ser Gln Arg Pro Leu Ser Ser Ser Ala Ser Asn Arg Leu Ser Val 1505 1510 1515 1520 Ser Ser Leu Leu Ala Ala Gly Ala Pro Met Ser Ser Ser Ala Ser Val 1525 1530 1535 Pro Asn Leu Ser Ser Arg Glu Thr Ser Ser Leu Glu Ser Phe Val Arg 1540 1545 1550 Arg Val Ala Asn Ile Ala Arg Thr Asn Ala Thr Asn Asn Met Asn Leu 1555 1560 1565 Ser Arg Ser Ser Ser Asp Asn Asn Thr Asn Thr Leu Gly Arg Asn Val 1570 1575 1580 Met Ser Thr Ala Thr Ser Pro Leu Met Gly Ala Gln Ser Phe Pro Asn 1585 1590 1595 1600 Leu Thr Thr Pro Gly Thr Thr Ser Thr Val Thr Met Ser Thr Ser Ser 1605 1610 1615 Val Thr Ser Ser Ser Asn Val Ala Thr Ala Thr Thr Val Leu Ser Val 1620 1625 1630 Gly Gln Ser Leu Ser Asn Thr Leu Thr Thr Ser Leu Thr Ser Thr Ser 1635 1640 1645 Ser Glu Ser Asp Thr Gly Gln Glu Ala Glu Tyr Ser Leu Tyr Asp Phe 1650 1655 1660 Leu Asp Ser Cys Arg Ala Ser Thr Leu Leu Ala Glu Leu Asp Asp Asp 1665 1670 1675 1680 Glu Asp Leu Pro Glu Pro Asp Glu Glu Asp Asp Glu Asn Glu Asp Asp 1685 1690 1695 Asn Gln Glu Asp Gln Glu Tyr Glu Glu Val Met Ile Leu Arg Arg Pro 1700 1705 1710 Ser Leu Gln Arg Arg Ala Gly Ser Arg Ser Asp Val Thr His His Ala 1715 1720 1725 Val Thr Ser Gln Leu Pro Gln Val Pro Ala Gly Ala Gly Ser Arg Pro 1730 1735 1740 Ile Gly Glu Gln Glu Glu Glu Glu Tyr Glu Thr Lys Gly Gly Arg Arg 1745 1750 1755 1760 Arg Thr Trp Asp Asp Asp Tyr Val Leu Lys Arg Gln Phe Ser Ala Leu 1765 1770 1775 Val Pro Ala Phe Asp Pro Arg Pro Gly Arg Thr Asn Val Gln Gln Thr 1780 1785 1790 Thr Asp Leu Glu Ile Pro Pro Pro Gly Thr Pro His Ser Glu Leu Leu 1795 1800 1805 Glu Glu Val Glu Cys Thr Pro Ser Pro Arg Leu Ala Leu Thr Leu Lys 1810 1815 1820 Val Thr Gly Leu Gly Thr Thr Arg Glu Val Glu Leu Pro Leu Thr Asn 1825 1830 1835 1840 Phe Arg Ser Thr Ile Phe Tyr Tyr Val Gln Lys Leu Leu Gln Leu Ser 1845 1850 1855 Cys Asn Gly Asn Val Lys Ser Asp Lys Leu Arg Arg Ile Trp Glu Pro 1860 1865 1870 Thr Tyr Thr Ile Met Tyr Arg Glu Met Lys Asp Ser Asp Lys Glu Lys 1875 1880 1885 Glu Asn Gly Lys Met Gly Cys Trp Ser Ile Glu His Val Glu Gln Tyr 1890 1895 1900 Leu Gly Thr Asp Glu Leu Pro Lys Asn Asp Leu Ile Thr Tyr Leu Gln 1905 1910 1915 1920 Lys Asn Ala Asp Ala Ala Phe Leu Arg His Trp Lys Leu Thr Gly Thr 1925 1930 1935 Asn Lys Ser Ile Arg Lys Asn Arg Asn Cys Ser Gln Leu Ile Ala Ala 1940 1945 1950 Tyr Lys Asp Phe Cys Glu His Gly Thr Lys Ser Gly Leu Asn Gln Gly 1955 1960 1965 Ala Ile Ser Thr Leu Gln Ser Ser Asp Ile Leu Asn Leu Thr Lys Glu 1970 1975 1980 Gln Pro Gln Ala Lys Ala Gly Asn Gly Gln Asn Ser Cys Gly Val Glu 1985 1990 1995 2000 Asp Val Leu Gln Leu Leu Arg Ile Leu Tyr Ile Val Ala Ser Asp Pro 2005 2010 2015 Tyr Ser Arg Ile Ser Gln Glu Asp Gly Asp Glu Gln Pro Gln Phe Thr 2020 2025 2030 Phe Pro Pro Asp Glu Phe Thr Ser Lys Lys Ile Thr Thr Lys Ile Leu 2035 2040 2045 Gln Gln Ile Glu Glu Pro Leu Ala Leu Ala Ser Gly Ala Leu Pro Asp 2050 2055 2060 Trp Cys Glu Gln Leu Thr Ser Lys Cys Pro Phe Leu Ile Pro Phe Glu 2065 2070 2075 2080 Thr Arg Gln Leu Tyr Phe Thr Cys Thr Ala Phe Gly Ala Ser Arg Ala 2085 2090 2095 Ile Val Trp Leu Gln Asn Arg Arg Glu Ala Thr Val Glu Arg Thr Arg 2100 2105 2110 Thr Thr Ser Ser Val Arg Arg Asp Asp Pro Gly Glu Phe Arg Val Gly 2115 2120 2125 Arg Leu Lys His Glu Arg Val Lys Val Pro Arg Gly Glu Ser Leu Met 2130 2135 2140 Glu Trp Ala Glu Asn Val Met Gln Ile His Ala Asp Arg Lys Ser Val 2145 2150 2155 2160 Leu Glu Val Glu Phe Leu Gly Glu Glu Gly Thr Gly Leu Gly Pro Thr 2165 2170 2175 Leu Glu Phe Tyr Ala Leu Val Ala Ala Glu Phe Gln Arg Thr Asp Leu 2180 2185 2190 Gly Ala Trp Leu Cys Asp Asp Asn Phe Pro Asp Asp Glu Ser Arg His 2195 2200 2205 Val Asp Leu Gly Gly Gly Leu Lys Pro Pro Gly Tyr Tyr Val Gln Arg 2210 2215 2220 Ser Cys Gly Leu Phe Thr Ala Pro Phe Pro Gln Asp Ser Asp Glu Leu 2225 2230 2235 2240 Glu Arg Ile Thr Lys Leu Phe His Phe Leu Gly Ile Phe Leu Ala Lys 2245 2250 2255 Cys Ile Gln Asp Asn Arg Leu Val Asp Leu Pro Ile Ser Lys Pro Phe 2260 2265 2270 Phe Lys Leu Met Cys Met Gly Asp Ile Lys Ser Asn Met Ser Lys Leu 2275 2280 2285 Ile Tyr Glu Ser Arg Gly Asp Arg Asp Leu His Cys Thr Glu Ser Gln 2290 2295 2300 Ser Glu Ala Ser Thr Glu Glu Gly His Asp Ser Leu Ser Val Gly Ser 2305 2310 2315 2320 Phe Glu Glu Asp Ser Lys Ser Glu Phe Ile Leu Asp Pro Pro Lys Pro 2325 2330 2335 Lys Pro Pro Ala Trp Phe Asn Gly Ile Leu Thr Trp Glu Asp Phe Glu 2340 2345 2350 Leu Val Asn Pro His Arg Ala Arg Phe Leu Lys Glu Ile Lys Asp Leu 2355 2360 2365 Ala Ile Lys Arg Arg Gln Ile Leu Ser Asn Lys Gly Leu Ser Glu Asp 2370 2375 2380 Glu Lys Asn Thr Lys Leu Gln Glu Leu Val Leu Lys Asn Pro Ser Gly 2385 2390 2395 2400 Ser Gly Pro Pro Leu Ser Ile Glu Asp Leu Gly Leu Asn Phe Gln Phe 2405 2410 2415 Cys Pro Ser Ser Arg Ile Tyr Gly Phe Thr Ala Val Asp Leu Lys Pro 2420 2425 2430 Ser Gly Glu Asp Glu Met Ile Thr Met Asp Asn Ala Glu Glu Tyr Val 2435 2440 2445 Asp Leu Met Phe Asp Phe Cys Met His Thr Gly Ile Gln Lys Gln Met 2450 2455 2460 Glu Ala Phe Arg Asp Gly Phe Asn Lys Val Phe Pro Met Glu Lys Leu 2465 2470 2475 2480 Ser Ser Phe Ser His Glu Glu Val Gln Met Ile Leu Cys Gly Asn Gln 2485 2490 2495 Ser Pro Ser Trp Ala Ala Glu Asp Ile Ile Asn Tyr Thr Glu Pro Lys 2500 2505 2510 Leu Gly Tyr Thr Arg Asp Ser Pro Gly Phe Leu Arg Phe Val Arg Val 2515 2520 2525 Leu Cys Gly Met Ser Ser Asp Glu Arg Lys Ala Phe Leu Gln Phe Thr 2530 2535 2540 Thr Gly Cys Ser Thr Leu Pro Pro Gly Gly Leu Ala Asn Leu His Pro 2545 2550 2555 2560 Arg Leu Thr Val Val Arg Lys Val Asp Ala Thr Asp Ala Ser Tyr Pro 2565 2570 2575 Ser Val Asn Thr Cys Val His Tyr Leu Lys Leu Pro Glu Tyr Ser Ser 2580 2585 2590 Glu Glu Ile Met Arg Glu Arg Leu Leu Ala Ala Thr Met Glu Lys Gly 2595 2600 2605 Phe His Leu Asn 2610 <210> 24 <211> 275 <212> PRT <213> Homo sapiens <400> 24 Met Leu Gly Gly Val Thr Leu Lys Leu Phe Tyr Leu Leu Pro Arg Thr 1 5 10 15 Ala Ala Ser Gly Ala Arg Ser Arg Pro Glu Pro Gly Thr Gln Val Arg 20 25 30 Ser Leu Asn Phe Arg Met Leu Thr Thr Leu Leu Pro Ile Leu Leu Leu 35 40 45 Ser Gly Trp Ala Phe Cys Ser Gln Asp Ala Ser Asp Gly Leu Gln Arg 50 55 60 Leu His Met Leu Gln Ile Ser Tyr Phe Arg Asp Pro Tyr His Val Trp 65 70 75 80 Tyr Gln Gly Asn Ala Ser Leu Gly Gly His Leu Thr His Val Leu Glu 85 90 95 Gly Pro Asp Thr Asn Thr Thr Ile Ile Gln Leu Gln Pro Leu Gln Glu 100 105 110 Pro Glu Ser Trp Ala Arg Thr Gln Ser Gly Leu Gln Ser Tyr Leu Leu 115 120 125 Gln Phe His Gly Leu Val Arg Leu Val His Gln Glu Arg Thr Leu Ala 130 135 140 Phe Pro Leu Thr Ile Arg Cys Phe Leu Gly Cys Glu Leu Pro Pro Glu 145 150 155 160 Gly Ser Arg Ala His Val Phe Phe Glu Val Ala Val Asn Gly Ser Ser 165 170 175 Phe Val Ser Phe Arg Pro Glu Arg Ala Leu Trp Gln Ala Asp Thr Gln 180 185 190 Val Thr Ser Gly Val Val Thr Phe Thr Leu Gln Gln Leu Asn Ala Tyr 195 200 205 Asn Arg Thr Arg Tyr Glu Leu Arg Glu Phe Leu Glu Asp Thr Cys Val 210 215 220 Gln Tyr Val Gln Lys His Ile Ser Ala Glu Asn Thr Lys Gly Ser Gln 225 230 235 240 Thr Ser Arg Ser Tyr Thr Ser Leu Val Leu Gly Val Leu Val Gly Ser 245 250 255 Phe Ile Ile Ala Gly Val Ala Val Gly Ile Phe Leu Cys Thr Gly Gly 260 265 270 Arg Arg Cys 275 <210> 25 <211> 182 <212> PRT <213> Homo sapiens <400> 25 Thr Thr Ala Ser Thr Ser Gln Val Arg Gln Asn Tyr His Gln Asp Ser 1 5 10 15 Glu Ala Ala Ile Asn Arg Gln Ile Asn Leu Glu Leu Tyr Ala Ser Tyr 20 25 30 Val Tyr Leu Ser Met Ser Tyr Tyr Phe Asp Arg Asp Asp Val Ala Leu 35 40 45 Lys Asn Phe Ala Lys Tyr Phe Leu His Gln Ser His Glu Glu Arg Glu 50 55 60 His Ala Glu Lys Leu Met Lys Leu Gln Asn Gln Arg Gly Gly Arg Ile 65 70 75 80 Phe Leu Gln Asp Ile Lys Lys Pro Asp Cys Asp Asp Trp Glu Ser Gly 85 90 95 Leu Asn Ala Met Glu Cys Ala Leu His Leu Glu Lys Asn Val Asn Gln 100 105 110 Ser Leu Leu Glu Leu His Lys Leu Ala Thr Asp Lys Asn Asp Pro His 115 120 125 Leu Cys Asp Phe Ile Glu Thr His Tyr Leu Asn Glu Gln Val Lys Ala 130 135 140 Ile Lys Glu Leu Gly Asp His Val Thr Asn Leu Arg Lys Met Gly Ala 145 150 155 160 Pro Glu Ser Gly Leu Ala Glu Tyr Leu Phe Asp Lys His Thr Leu Gly 165 170 175 Asp Ser Asp Asn Glu Ser 180 <210> 26 <211> 191 <212> PRT <213> Homo sapiens <400> 26 Met Ser Ser Gln Ile Arg Gln Asn Tyr Ser Thr Asp Val Glu Ala Ala 1 5 10 15 Val Asn Ser Leu Val Asn Leu Tyr Leu Gln Ala Ser Tyr Thr Tyr Leu 20 25 30 Ser Leu Gly Phe Tyr Phe Asp Arg Asp Asp Val Ala Leu Glu Gly Val 35 40 45 Ser His Phe Phe Arg Glu Leu Ala Glu Glu Lys Arg Glu Gly Tyr Glu 50 55 60 Arg Leu Leu Lys Met Gln Asn Gln Arg Gly Gly Arg Ala Leu Phe Gln 65 70 75 80 Asp Ile Lys Lys Pro Ala Glu Asp Glu Trp Gly Lys Thr Pro Asp Ala 85 90 95 Met Lys Ala Ala Met Ala Leu Glu Lys Lys Leu Asn Gln Ala Leu Leu 100 105 110 Asp Leu His Ala Leu Gly Ser Ala Arg Thr Asp Pro His Leu Cys Asp 115 120 125 Phe Leu Glu Thr His Phe Leu Asp Glu Glu Val Lys Leu Ile Lys Lys 130 135 140 Met Gly Asp His Leu Thr Asn Leu His Arg Leu Gly Gly Pro Glu Ala 145 150 155 160 Gly Leu Gly Glu Tyr Leu Ser Ser Lys Gly Ser Leu Ser Ser Thr Thr 165 170 175 Lys Ser Leu Leu Ser Pro Ala Thr Ser Glu Gly Pro Leu Ala Lys 180 185 190 <210> 27 <211> 382 <212> PRT <213> Homo sapiens <400> 27 Met Gly Leu Leu Leu Pro Leu Ala Leu Cys Ile Leu Val Leu Cys Cys 1 5 10 15 Gly Ala Met Ser Pro Pro Gln Leu Ala Leu Asn Pro Ser Ala Leu Leu 20 25 30 Ser Arg Gly Cys Asn Asp Ser Asp Val Leu Ala Val Ala Gly Phe Ala 35 40 45 Leu Arg Asp Ile Asn Lys Asp Arg Lys Asp Gly Tyr Val Leu Arg Leu 50 55 60 Asn Arg Val Asn Asp Ala Gln Glu Tyr Arg Arg Gly Gly Leu Gly Ser 65 70 75 80 Leu Phe Tyr Leu Thr Leu Asp Val Leu Glu Thr Asp Cys His Val Leu 85 90 95 Arg Lys Lys Ala Trp Gln Asp Cys Gly Met Arg Ile Phe Phe Glu Ser 100 105 110 Val Tyr Gly Gln Cys Lys Ala Ile Phe Tyr Met Asn Asn Pro Ser Arg 115 120 125 Val Leu Tyr Leu Ala Ala Tyr Asn Cys Thr Leu Arg Pro Val Ser Lys 130 135 140 Lys Lys Ile Tyr Met Thr Cys Pro Asp Cys Pro Ser Ser Ile Pro Thr 145 150 155 160 Asp Ser Ser Asn His Gln Val Leu Glu Ala Ala Thr Glu Ser Leu Ala 165 170 175 Lys Tyr Asn Asn Glu Asn Thr Ser Lys Gln Tyr Ser Leu Phe Lys Val 180 185 190 Thr Arg Ala Ser Ser Gln Trp Val Val Gly Pro Ser Tyr Phe Val Glu 195 200 205 Tyr Leu Ile Lys Glu Ser Pro Cys Thr Lys Ser Gln Ala Ser Ser Cys 210 215 220 Ser Leu Gln Ser Ser Asp Ser Val Pro Val Gly Leu Cys Lys Gly Ser 225 230 235 240 Leu Thr Arg Thr His Trp Glu Lys Phe Val Ser Val Thr Cys Asp Phe 245 250 255 Phe Glu Ser Gln Ala Pro Ala Thr Gly Ser Glu Asn Ser Ala Val Asn 260 265 270 Gln Lys Pro Thr Asn Leu Pro Lys Val Glu Glu Ser Gln Gln Lys Asn 275 280 285 Thr Pro Pro Thr Asp Ser Pro Ser Lys Ala Gly Pro Arg Gly Ser Val 290 295 300 Gln Tyr Leu Pro Asp Leu Asp Asp Lys Asn Ser Gln Glu Lys Gly Pro 305 310 315 320 Gln Glu Ala Phe Pro Val His Leu Asp Leu Thr Thr Asn Pro Gln Gly 325 330 335 Glu Thr Leu Asp Ile Ser Phe Leu Phe Leu Glu Pro Met Glu Glu Lys 340 345 350 Leu Val Val Leu Pro Phe Pro Lys Glu Lys Ala Arg Thr Ala Glu Cys 355 360 365 Pro Gly Pro Ala Gln Asn Ala Ser Pro Leu Val Leu Pro Pro 370 375 380 <210> 28 <211> 2330 <212> PRT <213> Homo sapiens <400> 28 Met Leu Arg Gly Pro Gly Pro Gly Leu Leu Leu Leu Ala Val Gln Cys 1 5 10 15 Leu Gly Thr Ala Val Pro Ser Thr Gly Ala Ser Lys Ser Lys Arg Gln 20 25 30 Ala Gln Gln Met Val Gln Pro Gln Ser Pro Val Ala Val Ser Gln Ser 35 40 45 Lys Pro Gly Cys Tyr Asp Asn Gly Lys His Tyr Gln Ile Asn Gln Gln 50 55 60 Trp Glu Arg Thr Tyr Leu Gly Asn Ala Leu Val Cys Thr Cys Tyr Gly 65 70 75 80 Gly Ser Arg Gly Phe Asn Cys Glu Ser Lys Pro Glu Ala Glu Glu Thr 85 90 95 Cys Phe Asp Lys Tyr Thr Gly Asn Thr Tyr Arg Val Gly Asp Thr Tyr 100 105 110 Glu Arg Pro Lys Asp Ser Met Ile Trp Asp Cys Thr Cys Ile Gly Ala 115 120 125 Gly Arg Gly Arg Ile Ser Cys Thr Ile Ala Asn Arg Cys His Glu Gly 130 135 140 Gly Gln Ser Tyr Lys Ile Gly Asp Thr Trp Arg Arg Pro His Glu Thr 145 150 155 160 Gly Gly Tyr Met Leu Glu Cys Val Cys Leu Gly Asn Gly Lys Gly Glu 165 170 175 Trp Thr Cys Lys Pro Ile Ala Glu Lys Cys Phe Asp His Ala Ala Gly 180 185 190 Thr Ser Tyr Val Val Gly Glu Thr Trp Glu Lys Pro Tyr Gln Gly Trp 195 200 205 Met Met Val Asp Cys Thr Cys Leu Gly Glu Gly Ser Gly Arg Ile Thr 210 215 220 Cys Thr Ser Arg Asn Arg Cys Asn Asp Gln Asp Thr Arg Thr Ser Tyr 225 230 235 240 Arg Ile Gly Asp Thr Trp Ser Lys Lys Asp Asn Arg Gly Asn Leu Leu 245 250 255 Gln Cys Ile Cys Thr Gly Asn Gly Arg Gly Glu Trp Lys Cys Glu Arg 260 265 270 His Thr Ser Val Gln Thr Thr Ser Ser Gly Ser Gly Pro Phe Thr Asp 275 280 285 Val Arg Ala Ala Val Tyr Gln Pro Gln Pro His Pro Gln Pro Pro Pro 290 295 300 Tyr Gly His Cys Val Thr Asp Ser Gly Val Val Tyr Ser Val Gly Met 305 310 315 320 Gln Trp Leu Lys Thr Gln Gly Asn Lys Gln Met Leu Cys Thr Cys Leu 325 330 335 Gly Asn Gly Val Ser Cys Gln Glu Thr Ala Val Thr Gln Thr Tyr Gly 340 345 350 Gly Asn Ser Asn Gly Glu Pro Cys Val Leu Pro Phe Thr Tyr Asn Gly 355 360 365 Arg Thr Phe Tyr Ser Cys Thr Thr Glu Gly Arg Gln Asp Gly His Leu 370 375 380 Trp Cys Ser Thr Thr Ser Asn Tyr Glu Gln Asp Gln Lys Tyr Ser Phe 385 390 395 400 Cys Thr Asp His Thr Val Leu Val Gln Thr Arg Gly Gly Asn Ser Asn 405 410 415 Gly Ala Leu Cys His Phe Pro Phe Leu Tyr Asn Asn His Asn Tyr Thr 420 425 430 Asp Cys Thr Ser Glu Gly Arg Arg Asp Asn Met Lys Trp Cys Gly Thr 435 440 445 Thr Gln Asn Tyr Asp Ala Asp Gln Lys Phe Gly Phe Cys Pro Met Ala 450 455 460 Ala His Glu Glu Ile Cys Thr Thr Asn Glu Gly Val Met Tyr Arg Ile 465 470 475 480 Gly Asp Gln Trp Asp Lys Gln His Asp Met Gly His Met Met Arg Cys 485 490 495 Thr Cys Val Gly Asn Gly Arg Gly Glu Trp Thr Cys Ile Ala Tyr Ser 500 505 510 Gln Leu Arg Asp Gln Cys Ile Val Asp Asp Ile Thr Tyr Asn Val Asn 515 520 525 Asp Thr Phe His Lys Arg His Glu Glu Gly His Met Leu Asn Cys Thr 530 535 540 Cys Phe Gly Gln Gly Arg Gly Arg Trp Lys Cys Asp Pro Val Asp Gln 545 550 555 560 Cys Gln Asp Ser Glu Thr Gly Thr Phe Tyr Gln Ile Gly Asp Ser Trp 565 570 575 Glu Lys Tyr Val His Gly Val Arg Tyr Gln Cys Tyr Cys Tyr Gly Arg 580 585 590 Gly Ile Gly Glu Trp His Cys Gln Pro Leu Gln Thr Tyr Pro Ser Ser 595 600 605 Ser Gly Pro Val Glu Val Phe Ile Thr Glu Thr Pro Ser Gln Pro Asn 610 615 620 Ser His Pro Ile Gln Trp Asn Ala Pro Gln Pro Ser His Ile Ser Lys 625 630 635 640 Tyr Ile Leu Arg Trp Arg Pro Lys Asn Ser Val Gly Arg Trp Lys Glu 645 650 655 Ala Thr Ile Pro Gly His Leu Asn Ser Tyr Thr Ile Lys Gly Leu Lys 660 665 670 Pro Gly Val Val Tyr Glu Gly Gln Leu Ile Ser Ile Gln Gln Tyr Gly 675 680 685 His Gln Glu Val Thr Arg Phe Asp Phe Thr Thr Thr Ser Thr Ser Thr 690 695 700 Pro Val Thr Ser Asn Thr Val Thr Gly Glu Thr Thr Pro Phe Ser Pro 705 710 715 720 Leu Val Ala Thr Ser Glu Ser Val Thr Glu Ile Thr Ala Ser Ser Phe 725 730 735 Val Val Ser Trp Val Ser Ala Ser Asp Thr Val Ser Gly Phe Arg Val 740 745 750 Glu Tyr Glu Leu Ser Glu Glu Gly Asp Glu Pro Gln Tyr Leu Asp Leu 755 760 765 Pro Ser Thr Ala Thr Ser Val Asn Ile Pro Asp Leu Leu Pro Gly Arg 770 775 780 Lys Tyr Ile Val Asn Val Tyr Gln Ile Ser Glu Asp Gly Glu Gln Ser 785 790 795 800 Leu Ile Leu Ser Thr Ser Gln Thr Thr Ala Pro Asp Ala Pro Pro Asp 805 810 815 Pro Thr Val Asp Gln Val Asp Asp Thr Ser Ile Val Val Arg Trp Ser 820 825 830 Arg Pro Gln Ala Pro Ile Thr Gly Tyr Arg Ile Val Tyr Ser Pro Ser 835 840 845 Val Glu Gly Ser Ser Thr Glu Leu Asn Leu Pro Glu Thr Ala Asn Ser 850 855 860 Val Thr Leu Ser Asp Leu Gln Pro Gly Val Gln Tyr Asn Ile Thr Ile 865 870 875 880 Tyr Ala Val Glu Glu Asn Gln Glu Ser Thr Pro Val Val Ile Gln Gln 885 890 895 Glu Thr Thr Gly Thr Pro Arg Ser Asp Thr Val Pro Ser Pro Arg Asp 900 905 910 Leu Gln Phe Val Glu Val Thr Asp Val Lys Val Thr Ile Met Trp Thr 915 920 925 Pro Pro Glu Ser Ala Val Thr Gly Tyr Arg Val Asp Val Ile Pro Val 930 935 940 Asn Leu Pro Gly Glu His Gly Gln Arg Leu Pro Ile Ser Arg Asn Thr 945 950 955 960 Phe Ala Glu Val Thr Gly Leu Ser Pro Gly Val Thr Tyr Tyr Phe Lys 965 970 975 Val Phe Ala Val Ser His Gly Arg Glu Ser Lys Pro Leu Thr Ala Gln 980 985 990 Gln Thr Thr Lys Leu Asp Ala Pro Thr Asn Leu Gln Phe Val Asn Glu 995 1000 1005 Thr Asp Ser Thr Val Leu Val Arg Trp Thr Pro Pro Arg Ala Gln Ile 1010 1015 1020 Thr Gly Tyr Arg Leu Thr Val Gly Leu Thr Arg Arg Gly Gln Pro Arg 1025 1030 1035 1040 Gln Tyr Asn Val Gly Pro Ser Val Ser Lys Tyr Pro Leu Arg Asn Leu 1045 1050 1055 Gln Pro Ala Ser Glu Tyr Thr Val Ser Leu Val Ala Ile Lys Gly Asn 1060 1065 1070 Gln Glu Ser Pro Lys Ala Thr Gly Val Phe Thr Thr Leu Gln Pro Gly 1075 1080 1085 Ser Ser Ile Pro Pro Tyr Asn Thr Glu Val Thr Glu Thr Thr Ile Val 1090 1095 1100 Ile Thr Trp Thr Pro Ala Pro Arg Ile Gly Phe Lys Leu Gly Val Arg 1105 1110 1115 1120 Pro Ser Gln Gly Gly Glu Ala Pro Arg Glu Val Thr Ser Asp Ser Gly 1125 1130 1135 Ser Ile Val Val Ser Gly Leu Thr Pro Gly Val Glu Tyr Val Tyr Thr 1140 1145 1150 Ile Gln Val Leu Arg Asp Gly Gln Glu Arg Asp Ala Pro Ile Val Asn 1155 1160 1165 Lys Val Val Thr Pro Leu Ser Pro Pro Thr Asn Leu His Leu Glu Ala 1170 1175 1180 Asn Pro Asp Thr Gly Val Leu Thr Val Ser Trp Glu Arg Ser Thr Thr 1185 1190 1195 1200 Pro Asp Ile Thr Gly Tyr Arg Ile Thr Thr Thr Pro Thr Asn Gly Gln 1205 1210 1215 Gln Gly Asn Ser Leu Glu Glu Val Val His Ala Asp Gln Ser Ser Cys 1220 1225 1230 Thr Phe Asp Asn Leu Ser Pro Gly Leu Glu Tyr Asn Val Ser Val Tyr 1235 1240 1245 Thr Val Lys Asp Asp Lys Glu Ser Val Pro Ile Ser Asp Thr Ile Ile 1250 1255 1260 Pro Ala Val Pro Pro Pro Thr Asp Leu Arg Phe Thr Asn Ile Gly Pro 1265 1270 1275 1280 Asp Thr Met Arg Val Thr Trp Ala Pro Pro Pro Ser Ile Asp Leu Thr 1285 1290 1295 Asn Phe Leu Val Arg Tyr Ser Pro Val Lys Asn Glu Glu Asp Val Ala 1300 1305 1310 Glu Leu Ser Ile Ser Pro Ser Asp Asn Ala Val Val Leu Thr Asn Leu 1315 1320 1325 Leu Pro Gly Thr Glu Tyr Val Val Ser Val Ser Ser Val Tyr Glu Gln 1330 1335 1340 His Glu Ser Thr Pro Leu Arg Gly Arg Gln Lys Thr Gly Leu Asp Ser 1345 1350 1355 1360 Pro Thr Gly Ile Asp Phe Ser Asp Ile Thr Ala Asn Ser Phe Thr Val 1365 1370 1375 His Trp Ile Ala Pro Arg Ala Thr Ile Thr Gly Tyr Arg Ile Arg His 1380 1385 1390 His Pro Glu His Phe Ser Gly Arg Pro Arg Glu Asp Arg Val Pro His 1395 1400 1405 Ser Arg Asn Ser Ile Thr Leu Thr Asn Leu Thr Pro Gly Thr Glu Tyr 1410 1415 1420 Val Val Ser Ile Val Ala Leu Asn Gly Arg Glu Glu Ser Pro Leu Leu 1425 1430 1435 1440 Ile Gly Gln Gln Ser Thr Val Ser Asp Val Pro Arg Asp Leu Glu Val 1445 1450 1455 Val Ala Ala Thr Pro Thr Ser Leu Leu Ile Ser Trp Asp Ala Pro Ala 1460 1465 1470 Val Thr Val Arg Tyr Tyr Arg Ile Thr Tyr Gly Glu Thr Gly Gly Asn 1475 1480 1485 Ser Pro Val Gln Glu Phe Thr Val Pro Gly Ser Lys Ser Thr Ala Thr 1490 1495 1500 Ile Ser Gly Leu Lys Pro Gly Val Asp Tyr Thr Ile Thr Val Tyr Ala 1505 1510 1515 1520 Val Thr Gly Arg Gly Asp Ser Pro Ala Ser Ser Lys Pro Ile Ser Ile 1525 1530 1535 Asn Tyr Arg Thr Glu Ile Asp Lys Pro Ser Gln Met Gln Val Thr Asp 1540 1545 1550 Val Gln Asp Asn Ser Ile Ser Val Lys Trp Leu Pro Ser Ser Ser Pro 1555 1560 1565 Val Thr Gly Tyr Arg Val Thr Thr Thr Pro Lys Asn Gly Pro Gly Pro 1570 1575 1580 Thr Lys Thr Lys Thr Ala Gly Pro Asp Gln Thr Glu Met Thr Ile Glu 1585 1590 1595 1600 Gly Leu Gln Pro Thr Val Glu Tyr Val Val Ser Val Tyr Ala Gln Asn 1605 1610 1615 Pro Ser Gly Glu Ser Gln Pro Leu Val Gln Thr Ala Val Thr Asn Ile 1620 1625 1630 Asp Arg Pro Lys Gly Leu Ala Phe Thr Asp Val Asp Val Asp Ser Ile 1635 1640 1645 Lys Ile Ala Trp Glu Ser Pro Gln Gly Gln Val Ser Arg Tyr Arg Val 1650 1655 1660 Thr Tyr Ser Ser Pro Glu Asp Gly Ile His Glu Leu Phe Pro Ala Pro 1665 1670 1675 1680 Asp Gly Glu Glu Asp Thr Ala Glu Leu Gln Gly Leu Arg Pro Gly Ser 1685 1690 1695 Glu Tyr Thr Val Ser Val Val Ala Leu His Asp Asp Met Glu Ser Gln 1700 1705 1710 Pro Leu Ile Gly Thr Gln Ser Thr Ala Ile Pro Ala Pro Thr Asp Leu 1715 1720 1725 Lys Phe Thr Gln Val Thr Pro Thr Ser Leu Ser Ala Gln Trp Thr Pro 1730 1735 1740 Pro Asn Val Gln Leu Thr Gly Tyr Arg Val Arg Val Thr Pro Lys Glu 1745 1750 1755 1760 Lys Thr Gly Pro Met Lys Glu Ile Asn Leu Ala Pro Asp Ser Ser Ser 1765 1770 1775 Val Val Val Ser Gly Leu Met Val Ala Thr Lys Tyr Glu Val Ser Val 1780 1785 1790 Tyr Ala Leu Lys Asp Thr Leu Thr Ser Arg Pro Ala Gln Gly Val Val 1795 1800 1805 Thr Thr Leu Glu Asn Val Ser Pro Pro Arg Arg Ala Arg Val Thr Asp 1810 1815 1820 Ala Thr Glu Thr Thr Ile Thr Ile Ser Trp Arg Thr Lys Thr Glu Thr 1825 1830 1835 1840 Ile Thr Gly Phe Gln Val Asp Ala Val Pro Ala Asn Gly Gln Thr Pro 1845 1850 1855 Ile Gln Arg Thr Ile Lys Pro Asp Val Arg Ser Tyr Thr Ile Thr Gly 1860 1865 1870 Leu Gln Pro Gly Thr Asp Tyr Lys Ile Tyr Leu Tyr Thr Leu Asn Asp 1875 1880 1885 Asn Ala Arg Ser Ser Pro Val Val Ile Asp Ala Ser Thr Ala Ile Asp 1890 1895 1900 Ala Pro Ser Asn Leu Arg Phe Leu Ala Thr Thr Pro Asn Ser Leu Leu 1905 1910 1915 1920 Val Ser Trp Gln Pro Pro Arg Ala Arg Ile Thr Gly Tyr Ile Ile Lys 1925 1930 1935 Tyr Glu Lys Pro Gly Ser Pro Pro Arg Glu Val Val Pro Arg Pro Arg 1940 1945 1950 Pro Gly Val Thr Glu Ala Thr Ile Thr Gly Leu Glu Pro Gly Thr Glu 1955 1960 1965 Tyr Thr Ile Tyr Val Ile Ala Leu Lys Asn Asn Gln Lys Ser Glu Pro 1970 1975 1980 Leu Ile Gly Arg Lys Lys Thr Val Gln Lys Thr Pro Phe Val Thr His 1985 1990 1995 2000 Pro Gly Tyr Asp Thr Gly Asn Gly Ile Gln Leu Pro Gly Thr Ser Gly 2005 2010 2015 Gln Gln Pro Ser Val Gly Gln Gln Met Ile Phe Glu Glu His Gly Phe 2020 2025 2030 Arg Arg Thr Thr Pro Pro Thr Thr Ala Thr Pro Ile Arg His Arg Pro 2035 2040 2045 Arg Pro Tyr Pro Pro Asn Val Gly Gln Glu Ala Leu Ser Gln Thr Thr 2050 2055 2060 Ile Ser Trp Ala Pro Phe Gln Asp Thr Ser Glu Tyr Ile Ile Ser Cys 2065 2070 2075 2080 His Pro Val Gly Thr Asp Glu Glu Pro Leu Gln Phe Arg Val Pro Gly 2085 2090 2095 Thr Ser Thr Ser Ala Thr Leu Thr Gly Leu Thr Arg Gly Ala Thr Tyr 2100 2105 2110 Asn Ile Ile Val Glu Ala Leu Lys Asp Gln Gln Arg His Lys Val Arg 2115 2120 2125 Glu Glu Val Val Thr Val Gly Asn Ser Val Asn Glu Gly Leu Asn Gln 2130 2135 2140 Pro Thr Asp Asp Ser Cys Phe Asp Pro Tyr Thr Val Ser His Tyr Ala 2145 2150 2155 2160 Val Gly Asp Glu Trp Glu Arg Met Ser Glu Ser Gly Phe Lys Leu Leu 2165 2170 2175 Cys Gln Cys Leu Gly Phe Gly Ser Gly His Phe Arg Cys Asp Ser Ser 2180 2185 2190 Arg Trp Cys His Asp Asn Gly Val Asn Tyr Lys Ile Gly Glu Lys Trp 2195 2200 2205 Asp Arg Gln Gly Glu Asn Gly Gln Met Met Ser Cys Thr Cys Leu Gly 2210 2215 2220 Asn Gly Lys Gly Glu Phe Lys Cys Asp Pro His Glu Ala Thr Cys Tyr 2225 2230 2235 2240 Asp Asp Gly Lys Thr Tyr His Val Gly Glu Gln Trp Gln Lys Glu Tyr 2245 2250 2255 Leu Gly Ala Ile Cys Ser Cys Thr Cys Phe Gly Gly Gln Arg Gly Trp 2260 2265 2270 Arg Cys Asp Asn Cys Arg Arg Pro Gly Gly Glu Pro Ser Pro Glu Gly 2275 2280 2285 Thr Thr Gly Gln Ser Tyr Asn Gln Tyr Ser Gln Arg Tyr His Gln Arg 2290 2295 2300 Thr Asn Thr Asn Val Asn Cys Pro Ile Glu Cys Phe Met Pro Leu Asp 2305 2310 2315 2320 Val Gln Ala Asp Arg Glu Asp Ser Arg Glu 2325 2330 <210> 29 <211> 363 <212> PRT <213> Homo sapiens <400> 29 Pro His Ser Tyr Pro Ala Leu Ser Ala Glu Gln Lys Lys Glu Leu Ser 1 5 10 15 Asp Ile Ala Leu Arg Ile Val Ala Pro Gly Lys Gly Ile Leu Ala Ala 20 25 30 Asp Glu Ser Val Gly Ser Met Ala Lys Arg Leu Ser Gln Ile Gly Val 35 40 45 Glu Asn Thr Glu Glu Asn Arg Arg Leu Tyr Arg Gln Val Leu Phe Ser 50 55 60 Ala Asp Asp Arg Val Lys Lys Cys Ile Gly Gly Val Ile Phe Phe His 65 70 75 80 Glu Thr Leu Tyr Gln Lys Asp Asp Asn Gly Val Pro Phe Val Arg Thr 85 90 95 Ile Gln Asp Lys Gly Ile Val Val Gly Ile Lys Val Asp Lys Gly Val 100 105 110 Val Pro Leu Ala Gly Thr Asp Gly Glu Thr Thr Thr Gln Gly Leu Asp 115 120 125 Gly Leu Ser Glu Arg Cys Ala Gln Tyr Lys Lys Asp Gly Ala Asp Phe 130 135 140 Ala Lys Trp Arg Cys Val Leu Lys Ile Ser Glu Arg Thr Pro Ser Ala 145 150 155 160 Leu Ala Ile Leu Glu Asn Ala Asn Val Leu Ala Arg Tyr Ala Ser Ile 165 170 175 Cys Gln Gln Asn Gly Ile Val Pro Ile Val Glu Pro Glu Ile Leu Pro 180 185 190 Asp Gly Asp His Asp Leu Lys Arg Cys Gln Tyr Val Thr Glu Lys Val 195 200 205 Leu Ala Ala Val Tyr Lys Ala Leu Ser Asp His His Val Tyr Leu Glu 210 215 220 Gly Thr Leu Leu Lys Pro Asn Met Val Thr Pro Gly His Ala Cys Pro 225 230 235 240 Ile Lys Tyr Thr Pro Glu Glu Ile Ala Met Ala Thr Val Thr Ala Leu 245 250 255 Arg Arg Thr Val Pro Pro Ala Val Pro Gly Val Thr Phe Leu Ser Gly 260 265 270 Gly Gln Ser Glu Glu Glu Ala Ser Phe Asn Leu Asn Ala Ile Asn Arg 275 280 285 Cys Pro Leu Pro Arg Pro Trp Ala Leu Thr Phe Ser Tyr Gly Arg Ala 290 295 300 Leu Gln Ala Ser Ala Leu Asn Ala Trp Arg Gly Gln Arg Asp Asn Ala 305 310 315 320 Gly Ala Ala Thr Glu Glu Phe Ile Lys Arg Ala Glu Val Asn Gly Leu 325 330 335 Ala Ala Gln Gly Lys Tyr Glu Gly Ser Gly Glu Asp Gly Gly Ala Ala 340 345 350 Ala Gln Ser Leu Tyr Ile Ala Asn His Ala Tyr 355 360 <210> 30 <211> 318 <212> PRT <213> Homo sapiens <400> 30 Met Ala Ser Pro Gly Cys Leu Leu Cys Val Leu Gly Leu Leu Leu Cys 1 5 10 15 Gly Ala Ala Ser Leu Glu Leu Ser Arg Pro His Gly Asp Thr Ala Lys 20 25 30 Lys Pro Ile Ile Gly Ile Leu Met Gln Lys Cys Arg Asn Lys Val Met 35 40 45 Lys Asn Tyr Gly Arg Tyr Tyr Ile Ala Ala Ser Tyr Val Lys Tyr Leu 50 55 60 Glu Ser Ala Gly Ala Arg Val Val Pro Val Arg Leu Asp Leu Thr Glu 65 70 75 80 Lys Asp Tyr Glu Ile Leu Phe Lys Ser Ile Asn Gly Ile Leu Phe Pro 85 90 95 Gly Gly Ser Val Asp Leu Arg Arg Ser Asp Tyr Ala Lys Val Ala Lys 100 105 110 Ile Phe Tyr Asn Leu Ser Ile Gln Ser Phe Asp Asp Gly Asp Tyr Phe 115 120 125 Pro Val Trp Gly Thr Cys Leu Gly Phe Glu Glu Leu Ser Leu Leu Ile 130 135 140 Ser Gly Glu Cys Leu Leu Thr Ala Thr Asp Thr Val Asp Val Ala Met 145 150 155 160 Pro Leu Asn Phe Thr Gly Gly Gln Leu His Ser Arg Met Phe Gln Asn 165 170 175 Phe Pro Thr Glu Leu Leu Leu Ser Leu Ala Val Glu Pro Leu Thr Ala 180 185 190 Asn Phe His Lys Trp Ser Leu Ser Val Lys Asn Phe Thr Met Asn Glu 195 200 205 Lys Leu Lys Lys Phe Phe Asn Val Leu Thr Thr Asn Thr Asp Gly Lys 210 215 220 Ile Glu Phe Ile Ser Thr Met Glu Gly Tyr Lys Tyr Pro Val Tyr Gly 225 230 235 240 Val Gln Trp His Pro Glu Lys Ala Pro Tyr Glu Trp Lys Asn Leu Asp 245 250 255 Gly Ile Ser His Ala Pro Asn Ala Val Lys Thr Ala Phe Tyr Leu Ala 260 265 270 Glu Phe Phe Val Asn Glu Ala Arg Lys Asn Asn His His Phe Lys Ser 275 280 285 Glu Ser Glu Glu Glu Lys Ala Leu Ile Tyr Gln Phe Ser Pro Ile Tyr 290 295 300 Thr Gly Asn Ile Ser Ser Phe Gln Gln Cys Tyr Ile Phe Asp 305 310 315 <210> 31 <211> 185 <212> PRT <213> Homo sapiens <400> 31 Met Lys Phe Thr Ile Val Phe Ala Gly Leu Leu Gly Val Phe Leu Ala 1 5 10 15 Pro Ala Leu Ala Asn Tyr Asn Ile Asn Val Asn Asp Asp Asn Asn Asn 20 25 30 Ala Gly Ser Gly Gln Gln Ser Val Ser Val Asn Asn Glu His Asn Val 35 40 45 Ala Asn Val Asp Asn Asn Asn Gly Trp Asp Ser Trp Asn Ser Ile Trp 50 55 60 Asp Tyr Gly Asn Gly Phe Ala Ala Thr Arg Leu Phe Gln Lys Lys Thr 65 70 75 80 Cys Ile Val His Lys Met Asn Lys Glu Val Met Pro Ser Ile Gln Ser 85 90 95 Leu Asp Ala Leu Val Lys Glu Lys Lys Leu Gln Gly Lys Gly Pro Gly 100 105 110 Gly Pro Pro Pro Lys Gly Leu Met Tyr Ser Val Asn Pro Asn Lys Val 115 120 125 Asp Asp Leu Ser Lys Phe Gly Lys Asn Ile Ala Asn Met Cys Arg Gly 130 135 140 Ile Pro Thr Tyr Met Ala Glu Glu Met Gln Glu Ala Ser Leu Phe Phe 145 150 155 160 Tyr Ser Gly Thr Cys Tyr Thr Thr Ser Val Leu Trp Ile Val Asp Ile 165 170 175 Ser Phe Cys Gly Asp Thr Val Glu Asn 180 185 <210> 32 <211> 375 <212> PRT <213> Homo sapiens <400> 32 Met Gln Lys Leu Gln Leu Cys Val Tyr Ile Tyr Leu Phe Met Leu Ile 1 5 10 15 Val Ala Gly Pro Val Asp Leu Asn Glu Asn Ser Glu Gln Lys Glu Asn 20 25 30 Val Glu Lys Glu Gly Leu Cys Asn Ala Cys Thr Trp Arg Gln Asn Thr 35 40 45 Lys Ser Ser Arg Ile Glu Ala Ile Lys Ile Gln Ile Leu Ser Lys Leu 50 55 60 Arg Leu Glu Thr Ala Pro Asn Ile Ser Lys Asp Val Ile Arg Gln Leu 65 70 75 80 Leu Pro Lys Ala Pro Pro Leu Arg Glu Leu Ile Asp Gln Tyr Asp Val 85 90 95 Gln Arg Asp Asp Ser Ser Asp Gly Ser Leu Glu Asp Asp Asp Tyr His 100 105 110 Ala Thr Thr Glu Thr Ile Ile Thr Met Pro Thr Glu Ser Asp Phe Leu 115 120 125 Met Gln Val Asp Gly Lys Pro Lys Cys Cys Phe Phe Lys Phe Ser Ser 130 135 140 Lys Ile Gln Tyr Asn Lys Val Val Lys Ala Gln Leu Trp Ile Tyr Leu 145 150 155 160 Arg Pro Val Glu Thr Pro Thr Thr Val Phe Val Gln Ile Leu Arg Leu 165 170 175 Ile Lys Pro Met Lys Asp Gly Thr Arg Tyr Thr Gly Ile Arg Ser Leu 180 185 190 Lys Leu Asp Met Asn Pro Gly Thr Gly Ile Trp Gln Ser Ile Asp Val 195 200 205 Lys Thr Val Leu Gln Asn Trp Leu Lys Gln Pro Glu Ser Asn Leu Gly 210 215 220 Ile Glu Ile Lys Ala Leu Asp Glu Asn Gly His Asp Leu Ala Val Thr 225 230 235 240 Phe Pro Gly Pro Gly Glu Asp Gly Leu Asn Pro Phe Leu Glu Val Lys 245 250 255 Val Thr Asp Thr Pro Lys Arg Ser Arg Arg Asp Phe Gly Leu Asp Cys 260 265 270 Asp Glu His Ser Thr Glu Ser Arg Cys Cys Arg Tyr Pro Leu Thr Val 275 280 285 Asp Phe Glu Ala Phe Gly Trp Asp Trp Ile Ile Ala Pro Lys Arg Tyr 290 295 300 Lys Ala Asn Tyr Cys Ser Gly Glu Cys Glu Phe Val Phe Leu Gln Lys 305 310 315 320 Tyr Pro His Thr His Leu Val His Gln Ala Asn Pro Arg Gly Ser Ala 325 330 335 Gly Pro Cys Cys Thr Pro Thr Lys Met Ser Pro Ile Asn Met Leu Tyr 340 345 350 Phe Asn Gly Lys Glu Gln Ile Ile Tyr Gly Lys Ile Pro Ala Met Val 355 360 365 Val Asp Arg Cys Gly Cys Ser 370 375 <210> 33 <211> 655 <212> PRT <213> Homo sapiens <400> 33 Met Gly Arg Trp Ala Trp Val Pro Ser Pro Trp Pro Pro Pro Gly Leu 1 5 10 15 Gly Pro Phe Leu Leu Leu Leu Leu Leu Leu Leu Leu Leu Pro Arg Gly 20 25 30 Phe Gln Pro Gln Pro Gly Gly Asn Arg Thr Glu Ser Pro Glu Pro Asn 35 40 45 Ala Thr Ala Thr Pro Ala Ile Pro Thr Ile Leu Val Thr Ser Val Thr 50 55 60 Ser Glu Thr Pro Ala Thr Ser Ala Pro Glu Ala Glu Gly Pro Gln Ser 65 70 75 80 Gly Gly Leu Pro Pro Pro Pro Arg Ala Val Pro Ser Ser Ser Ser Pro 85 90 95 Gln Ala Gln Ala Leu Thr Glu Asp Gly Arg Pro Cys Arg Phe Pro Phe 100 105 110 Arg Tyr Gly Gly Arg Met Leu His Ala Cys Thr Ser Glu Gly Ser Ala 115 120 125 His Arg Lys Trp Cys Ala Thr Thr His Asn Tyr Asp Arg Asp Arg Ala 130 135 140 Trp Gly Tyr Cys Val Glu Ala Thr Pro Pro Pro Gly Gly Pro Ala Ala 145 150 155 160 Leu Asp Pro Cys Ala Ser Gly Pro Cys Leu Asn Gly Gly Ser Cys Ser 165 170 175 Asn Thr Gln Asp Pro Gln Ser Tyr His Cys Ser Cys Pro Arg Ala Phe 180 185 190 Thr Gly Lys Asp Cys Gly Thr Glu Lys Cys Phe Asp Glu Thr Arg Tyr 195 200 205 Glu Tyr Leu Glu Gly Gly Asp Arg Trp Ala Arg Val Arg Gln Gly His 210 215 220 Val Glu Gln Cys Glu Cys Phe Gly Gly Arg Thr Trp Cys Glu Gly Thr 225 230 235 240 Arg His Thr Ala Cys Leu Ser Ser Pro Cys Leu Asn Gly Gly Thr Cys 245 250 255 His Leu Ile Val Ala Thr Gly Thr Thr Val Cys Ala Cys Pro Pro Gly 260 265 270 Phe Ala Gly Arg Leu Cys Asn Ile Glu Pro Asp Glu Arg Cys Phe Leu 275 280 285 Gly Asn Gly Thr Gly Tyr Arg Gly Val Ala Ser Thr Ser Ala Ser Gly 290 295 300 Leu Ser Cys Leu Ala Trp Asn Ser Asp Leu Leu Tyr Gln Glu Leu His 305 310 315 320 Val Asp Ser Val Gly Ala Ala Ala Leu Leu Gly Leu Gly Pro His Ala 325 330 335 Tyr Cys Arg Asn Pro Asp Asn Asp Glu Arg Pro Trp Cys Tyr Val Val 340 345 350 Lys Asp Ser Ala Leu Ser Trp Glu Tyr Cys Arg Leu Glu Ala Cys Glu 355 360 365 Ser Leu Thr Arg Val Gln Leu Ser Pro Asp Leu Leu Ala Thr Leu Pro 370 375 380 Glu Pro Ala Ser Pro Gly Arg Gln Ala Cys Gly Arg Arg His Lys Lys 385 390 395 400 Arg Thr Phe Leu Arg Pro Arg Ile Ile Gly Gly Ser Ser Ser Leu Pro 405 410 415 Gly Ser His Pro Trp Leu Ala Ala Ile Tyr Ile Gly Asp Ser Phe Cys 420 425 430 Ala Gly Ser Leu Val His Thr Cys Trp Val Val Ser Ala Ala His Cys 435 440 445 Phe Ser His Ser Pro Pro Arg Asp Ser Val Ser Val Val Leu Gly Gln 450 455 460 His Phe Phe Asn Arg Thr Thr Asp Val Thr Gln Thr Phe Gly Ile Glu 465 470 475 480 Lys Tyr Ile Pro Tyr Thr Leu Tyr Ser Val Phe Asn Pro Ser Asp His 485 490 495 Asp Leu Val Leu Ile Arg Leu Lys Lys Lys Gly Asp Arg Cys Ala Thr 500 505 510 Arg Ser Gln Phe Val Gln Pro Ile Cys Leu Pro Glu Pro Gly Ser Thr 515 520 525 Phe Pro Ala Gly His Lys Cys Gln Ile Ala Gly Trp Gly His Leu Asp 530 535 540 Glu Asn Val Ser Gly Tyr Ser Ser Ser Leu Arg Glu Ala Leu Val Pro 545 550 555 560 Leu Val Ala Asp His Lys Cys Ser Ser Pro Glu Val Tyr Gly Ala Asp 565 570 575 Ile Ser Pro Asn Met Leu Cys Ala Gly Tyr Phe Asp Cys Lys Ser Asp 580 585 590 Ala Cys Gln Gly Asp Ser Gly Gly Pro Leu Ala Cys Glu Lys Asn Gly 595 600 605 Val Ala Tyr Leu Tyr Gly Ile Ile Ser Trp Gly Asp Gly Cys Gly Arg 610 615 620 Leu His Lys Pro Gly Val Tyr Thr Arg Val Ala Asn Tyr Val Asp Trp 625 630 635 640 Ile Asn Asp Arg Ile Arg Pro Pro Arg Arg Leu Val Ala Pro Ser 645 650 655 <210> 34 <211> 2850 <212> PRT <213> Homo sapiens <400> 34 Met Pro Lys Leu Leu Gln Gly Val Ile Thr Val Ile Asp Val Phe Tyr 1 5 10 15 Gln Tyr Ala Thr Gln His Gly Glu Tyr Asp Thr Leu Asn Lys Ala Glu 20 25 30 Leu Lys Glu Leu Leu Glu Asn Glu Phe His Gln Ile Leu Lys Asn Pro 35 40 45 Asn Asp Pro Asp Thr Val Asp Ile Ile Leu Gln Ser Leu Asp Arg Asp 50 55 60 His Asn Lys Lys Val Asp Phe Thr Glu Tyr Leu Leu Met Ile Phe Lys 65 70 75 80 Leu Val Gln Ala Arg Asn Lys Ile Ile Gly Lys Asp Tyr Cys Gln Val 85 90 95 Ser Gly Ser Lys Leu Arg Asp Asp Thr His Gln His Gln Glu Glu Gln 100 105 110 Glu Glu Thr Glu Lys Glu Glu Asn Lys Arg Gln Glu Ser Ser Phe Ser 115 120 125 His Ser Ser Trp Ser Ala Gly Glu Asn Asp Ser Tyr Ser Arg Asn Val 130 135 140 Arg Gly Ser Leu Lys Pro Gly Thr Glu Ser Ile Ser Arg Arg Leu Ser 145 150 155 160 Phe Gln Arg Asp Phe Ser Gly Gln His Asn Ser Tyr Ser Gly Gln Ser 165 170 175 Ser Ser Tyr Gly Glu Gln Asn Ser Asp Ser His Gln Ser Ser Gly Arg 180 185 190 Gly Gln Cys Gly Ser Gly Ser Gly Gln Ser Pro Asn Tyr Gly Gln His 195 200 205 Gly Ser Gly Ser Gly Gln Ser Ser Ser Asn Asp Thr His Gly Ser Gly 210 215 220 Ser Gly Gln Ser Ser Gly Phe Ser Gln His Lys Ser Ser Ser Gly Gln 225 230 235 240 Ser Ser Gly Tyr Ser Gln His Gly Ser Gly Ser Gly His Ser Ser Gly 245 250 255 Tyr Gly Gln His Gly Ser Arg Ser Gly Gln Ser Ser Arg Gly Glu Arg 260 265 270 His Arg Ser Ser Ser Gly Ser Ser Ser Ser Tyr Gly Gln His Gly Ser 275 280 285 Gly Ser Arg Gln Ser Leu Gly His Gly Arg Gln Gly Ser Gly Ser Arg 290 295 300 Gln Ser Pro Ser His Val Arg His Gly Ser Gly Ser Gly His Ser Ser 305 310 315 320 Ser His Gly Gln His Gly Ser Gly Ser Ser Tyr Ser Tyr Ser Arg Gly 325 330 335 His Tyr Glu Ser Gly Ser Gly Gln Thr Ser Gly Phe Gly Gln His Glu 340 345 350 Ser Gly Ser Gly Gln Ser Ser Gly Tyr Ser Lys His Gly Ser Gly Ser 355 360 365 Gly His Ser Ser Ser Gln Gly Gln His Gly Ser Thr Ser Gly Gln Ala 370 375 380 Ser Ser Ser Gly Gln His Gly Ser Ser Ser Arg Gln Ser Ser Ser Tyr 385 390 395 400 Gly Gln His Glu Ser Ala Ser Arg His Ser Ser Gly Arg Gly Gln His 405 410 415 Ser Ser Gly Ser Gly Gln Ser Pro Gly His Gly Gln Arg Gly Ser Gly 420 425 430 Ser Gly Gln Ser Pro Ser Ser Gly Gln His Gly Thr Gly Phe Gly Arg 435 440 445 Ser Ser Ser Ser Gly Pro Tyr Val Ser Gly Ser Gly Tyr Ser Ser Gly 450 455 460 Phe Gly His His Glu Ser Ser Ser Glu His Ser Ser Gly Tyr Thr Gln 465 470 475 480 His Gly Ser Gly Ser Gly His Ser Ser Gly His Gly Gln His Gly Ser 485 490 495 Arg Ser Gly Gln Ser Ser Arg Gly Glu Arg Gln Gly Ser Ser Ala Gly 500 505 510 Ser Ser Ser Ser Tyr Gly Gln His Gly Ser Gly Ser Arg Gln Ser Leu 515 520 525 Gly His Ser Arg His Gly Ser Gly Ser Gly Gln Ser Pro Ser Pro Ser 530 535 540 Arg Gly Arg His Glu Ser Gly Ser Arg Gln Ser Ser Ser Tyr Gly Pro 545 550 555 560 His Gly Tyr Gly Ser Gly Arg Ser Ser Ser Arg Gly Pro Tyr Glu Ser 565 570 575 Gly Ser Gly His Ser Ser Gly Leu Gly His Gln Glu Ser Arg Ser Gly 580 585 590 Gln Ser Ser Gly Tyr Gly Gln His Gly Ser Ser Ser Gly His Ser Ser 595 600 605 Thr His Gly Gln His Gly Ser Thr Ser Gly Gln Ser Ser Ser Cys Gly 610 615 620 Gln His Gly Ala Thr Ser Gly Gln Ser Ser Ser His Gly Gln His Gly 625 630 635 640 Ser Gly Ser Ser Gln Ser Ser Arg Tyr Gly Gln Gln Gly Ser Gly Ser 645 650 655 Gly Gln Ser Pro Ser Arg Gly Arg His Gly Ser Asp Phe Gly His Ser 660 665 670 Ser Ser Tyr Gly Gln His Gly Ser Gly Ser Gly Trp Ser Ser Ser Asn 675 680 685 Gly Pro His Gly Ser Val Ser Gly Gln Ser Ser Gly Phe Gly His Lys 690 695 700 Ser Gly Ser Gly Gln Ser Ser Gly Tyr Ser Gln His Gly Ser Gly Ser 705 710 715 720 Ser His Ser Ser Gly Tyr Arg Lys His Gly Ser Arg Ser Gly Gln Ser 725 730 735 Ser Arg Ser Glu Gln His Gly Ser Ser Ser Gly Leu Ser Ser Ser Tyr 740 745 750 Gly Gln His Gly Ser Gly Ser His Gln Ser Ser Gly His Gly Arg Gln 755 760 765 Gly Ser Gly Ser Gly His Ser Pro Ser Arg Val Arg His Gly Ser Ser 770 775 780 Ser Gly His Ser Ser Ser His Gly Gln His Gly Ser Gly Thr Ser Cys 785 790 795 800 Ser Ser Ser Cys Gly His Tyr Glu Ser Gly Ser Gly Gln Ala Ser Gly 805 810 815 Phe Gly Gln His Glu Ser Gly Ser Gly Gln Gly Tyr Ser Gln His Gly 820 825 830 Ser Ala Ser Gly His Phe Ser Ser Gln Gly Arg His Gly Ser Thr Ser 835 840 845 Gly Gln Ser Ser Ser Ser Gly Gln His Asp Ser Ser Ser Gly Gln Ser 850 855 860 Ser Ser Tyr Gly Gln His Glu Ser Ala Ser His His Ala Ser Gly Arg 865 870 875 880 Gly Arg His Gly Ser Gly Ser Gly Gln Ser Pro Gly His Gly Gln Arg 885 890 895 Gly Ser Gly Ser Gly Gln Ser Pro Ser Tyr Gly Arg His Gly Ser Gly 900 905 910 Ser Gly Arg Ser Ser Ser Ser Gly Arg His Gly Ser Gly Ser Gly Gln 915 920 925 Ser Ser Gly Phe Gly His Lys Ser Ser Ser Gly Gln Ser Ser Gly Tyr 930 935 940 Thr Gln His Gly Ser Gly Ser Gly His Ser Ser Ser Tyr Glu Gln His 945 950 955 960 Gly Ser Arg Ser Gly Gln Ser Ser Arg Ser Glu Gln His Gly Ser Ser 965 970 975 Ser Gly Ser Ser Ser Ser Tyr Gly Gln His Gly Ser Gly Ser Arg Gln 980 985 990 Ser Leu Gly His Gly Gln His Gly Ser Gly Ser Gly Gln Ser Pro Ser 995 1000 1005 Pro Ser Arg Gly Arg His Gly Ser Gly Ser Gly Gln Ser Ser Ser Tyr 1010 1015 1020 Gly Pro Tyr Arg Ser Gly Ser Gly Trp Ser Ser Ser Arg Gly Pro Tyr 1025 1030 1035 1040 Glu Ser Gly Ser Gly His Ser Ser Gly Leu Gly His Arg Glu Ser Arg 1045 1050 1055 Ser Gly Gln Ser Ser Gly Tyr Gly Gln His Gly Ser Ser Ser Gly His 1060 1065 1070 Ser Ser Thr His Gly Gln His Gly Ser Thr Ser Gly Gln Ser Ser Ser 1075 1080 1085 Cys Gly Gln His Gly Ala Ser Ser Gly Gln Ser Ser Ser His Gly Gln 1090 1095 1100 His Gly Ser Gly Ser Ser Gln Ser Ser Gly Tyr Gly Arg Gln Gly Ser 1105 1110 1115 1120 Gly Ser Gly Gln Ser Pro Gly His Gly Gln Arg Gly Ser Gly Ser Arg 1125 1130 1135 Gln Ser Pro Ser Tyr Gly Arg His Gly Ser Gly Ser Gly Arg Ser Ser 1140 1145 1150 Ser Ser Gly Gln His Gly Ser Gly Leu Gly Glu Ser Ser Gly Phe Gly 1155 1160 1165 His His Glu Ser Ser Ser Gly Gln Ser Ser Ser Tyr Ser Gln His Gly 1170 1175 1180 Ser Gly Ser Gly His Ser Ser Gly Tyr Gly Gln His Gly Ser Arg Ser 1185 1190 1195 1200 Gly Gln Ser Ser Arg Gly Glu Arg His Gly Ser Ser Ser Gly Ser Ser 1205 1210 1215 Ser His Tyr Gly Gln His Gly Ser Gly Ser Arg Gln Ser Ser Gly His 1220 1225 1230 Gly Arg Gln Gly Ser Gly Ser Gly His Ser Pro Ser Arg Gly Arg His 1235 1240 1245 Gly Ser Gly Leu Gly His Ser Ser Ser His Gly Gln His Gly Ser Gly 1250 1255 1260 Ser Gly Arg Ser Ser Ser Arg Gly Pro Tyr Glu Ser Arg Ser Gly His 1265 1270 1275 1280 Ser Ser Val Phe Gly Gln His Glu Ser Gly Ser Gly His Ser Ser Ala 1285 1290 1295 Tyr Ser Gln His Gly Ser Gly Ser Gly His Phe Cys Ser Gln Gly Gln 1300 1305 1310 His Gly Ser Thr Ser Gly Gln Ser Ser Thr Phe Asp Gln Glu Gly Ser 1315 1320 1325 Ser Thr Gly Gln Ser Ser Ser Tyr Gly His Arg Gly Ser Gly Ser Ser 1330 1335 1340 Gln Ser Ser Gly Tyr Gly Arg His Gly Ala Gly Ser Gly Gln Ser Pro 1345 1350 1355 1360 Ser Arg Gly Arg His Gly Ser Gly Ser Gly His Ser Ser Ser Tyr Gly 1365 1370 1375 Gln His Gly Ser Gly Ser Gly Trp Ser Ser Ser Ser Gly Arg His Gly 1380 1385 1390 Ser Gly Ser Gly Gln Ser Ser Gly Phe Gly His His Glu Ser Ser Ser 1395 1400 1405 Trp Gln Ser Ser Gly Cys Thr Gln His Gly Ser Gly Ser Gly His Ser 1410 1415 1420 Ser Ser Tyr Glu Gln His Gly Ser Arg Ser Gly Gln Ser Ser Arg Gly 1425 1430 1435 1440 Glu Arg His Gly Ser Ser Ser Gly Ser Ser Ser Ser Tyr Gly Gln His 1445 1450 1455 Gly Ser Gly Ser Arg Gln Ser Leu Gly His Gly Gln His Gly Ser Gly 1460 1465 1470 Ser Gly Gln Ser Pro Ser Pro Ser Arg Gly Arg His Gly Ser Gly Ser 1475 1480 1485 Gly Gln Ser Ser Ser Tyr Ser Pro Tyr Gly Ser Gly Ser Gly Trp Ser 1490 1495 1500 Ser Ser Arg Gly Pro Tyr Glu Ser Gly Ser Ser His Ser Ser Gly Leu 1505 1510 1515 1520 Gly His Arg Glu Ser Arg Ser Gly Gln Ser Ser Gly Tyr Gly Gln His 1525 1530 1535 Gly Ser Ser Ser Gly His Ser Ser Thr His Gly Gln His Gly Ser Thr 1540 1545 1550 Ser Gly Gln Ser Ser Ser Cys Gly Gln His Gly Ala Ser Ser Gly Gln 1555 1560 1565 Ser Ser Ser His Gly Gln His Gly Ser Gly Ser Ser Gln Ser Ser Gly 1570 1575 1580 Tyr Gly Arg Gln Gly Ser Gly Ser Gly Gln Ser Pro Gly His Gly Gln 1585 1590 1595 1600 Arg Gly Ser Gly Ser Arg Gln Ser Pro Ser Tyr Gly Arg His Gly Ser 1605 1610 1615 Gly Ser Gly Arg Ser Ser Ser Ser Gly Gln His Gly Ser Gly Leu Gly 1620 1625 1630 Glu Ser Ser Gly Phe Gly His His Glu Ser Ser Ser Gly Gln Ser Ser 1635 1640 1645 Ser Tyr Ser Gln His Gly Ser Gly Ser Gly His Ser Ser Gly Tyr Gly 1650 1655 1660 Gln His Gly Ser Arg Ser Gly Gln Ser Ser Arg Gly Glu Arg His Gly 1665 1670 1675 1680 Ser Ser Ser Arg Ser Ser Ser Arg Tyr Gly Gln His Gly Ser Gly Ser 1685 1690 1695 Arg Gln Ser Ser Gly His Gly Arg Gln Gly Ser Gly Ser Gly Gln Ser 1700 1705 1710 Pro Ser Arg Gly Arg His Gly Ser Gly Leu Gly His Ser Ser Ser His 1715 1720 1725 Gly Gln His Gly Ser Gly Ser Gly Arg Ser Ser Ser Arg Gly Pro Tyr 1730 1735 1740 Glu Ser Arg Ser Gly His Ser Ser Val Phe Gly Gln His Glu Ser Gly 1745 1750 1755 1760 Ser Gly His Ser Ser Ala Tyr Ser Gln His Gly Ser Gly Ser Gly His 1765 1770 1775 Phe Cys Ser Gln Gly Gln His Gly Ser Thr Ser Gly Gln Ser Ser Thr 1780 1785 1790 Phe Asp Gln Glu Gly Ser Ser Thr Gly Gln Ser Ser Ser His Gly Gln 1795 1800 1805 His Gly Ser Gly Ser Ser Gln Ser Ser Ser Tyr Gly Gln Gln Gly Ser 1810 1815 1820 Gly Ser Gly Gln Ser Pro Ser Arg Gly Arg His Gly Ser Gly Ser Gly 1825 1830 1835 1840 His Ser Ser Ser Tyr Gly Gln His Gly Ser Gly Ser Gly Trp Ser Ser 1845 1850 1855 Ser Ser Gly Arg His Gly Ser Gly Ser Gly Gln Ser Ser Gly Phe Gly 1860 1865 1870 His His Glu Ser Ser Ser Trp Gln Ser Ser Gly Tyr Thr Gln His Gly 1875 1880 1885 Ser Gly Ser Gly His Ser Ser Ser Tyr Glu Gln His Gly Ser Arg Ser 1890 1895 1900 Gly Gln Ser Ser Arg Gly Glu Gln His Gly Ser Ser Ser Gly Ser Ser 1905 1910 1915 1920 Ser Ser Tyr Gly Gln His Gly Ser Gly Ser Arg Gln Ser Leu Gly His 1925 1930 1935 Gly Gln His Gly Ser Gly Ser Gly Gln Ser Pro Ser Pro Ser Arg Gly 1940 1945 1950 Arg His Gly Ser Gly Ser Gly Gln Ser Ser Ser Tyr Gly Pro Tyr Gly 1955 1960 1965 Ser Gly Ser Gly Trp Ser Ser Ser Arg Gly Pro Tyr Glu Ser Gly Ser 1970 1975 1980 Gly His Ser Ser Gly Leu Gly His Arg Glu Ser Arg Ser Gly Gln Ser 1985 1990 1995 2000 Ser Gly Tyr Gly Gln His Gly Ser Ser Ser Gly His Ser Ser Thr His 2005 2010 2015 Gly Gln His Gly Ser Ala Ser Gly Gln Ser Ser Ser Cys Gly Gln His 2020 2025 2030 Gly Ala Ser Ser Gly Gln Ser Ser Ser His Gly Gln His Gly Ser Gly 2035 2040 2045 Ser Ser Gln Ser Ser Gly Tyr Gly Arg Gln Gly Ser Gly Ser Gly Gln 2050 2055 2060 Ser Pro Gly His Gly Gln Arg Gly Ser Gly Ser Arg Gln Ser Pro Ser 2065 2070 2075 2080 Tyr Gly Arg His Gly Ser Gly Ser Gly Arg Ser Ser Ser Ser Gly Gln 2085 2090 2095 His Gly Pro Gly Leu Gly Glu Ser Ser Gly Phe Gly His His Glu Ser 2100 2105 2110 Ser Ser Gly Gln Ser Ser Ser Tyr Ser Gln His Gly Ser Gly Ser Gly 2115 2120 2125 His Ser Ser Gly Tyr Gly Gln His Gly Ser Arg Ser Gly Gln Ser Ser 2130 2135 2140 Arg Gly Glu Arg His Gly Ser Ser Ser Gly Ser Ser Ser Arg Tyr Gly 2145 2150 2155 2160 Gln His Gly Ser Gly Ser Arg Gln Ser Ser Gly His Gly Arg Gln Gly 2165 2170 2175 Ser Gly Ser Gly His Ser Pro Ser Arg Gly Arg His Gly Ser Gly Ser 2180 2185 2190 Gly His Ser Ser Ser His Gly Gln His Gly Ser Gly Ser Gly Arg Ser 2195 2200 2205 Ser Ser Arg Gly Pro Tyr Glu Ser Arg Ser Gly His Ser Ser Val Phe 2210 2215 2220 Gly Gln His Glu Ser Gly Ser Gly His Ser Ser Ala Tyr Ser Gln His 2225 2230 2235 2240 Gly Ser Gly Ser Gly His Phe Cys Ser Gln Gly Gln His Gly Ser Thr 2245 2250 2255 Ser Gly Gln Ser Ser Thr Phe Asp Gln Glu Gly Ser Ser Thr Gly Gln 2260 2265 2270 Ser Ser Ser His Gly Gln His Gly Ser Gly Ser Ser Gln Ser Ser Ser 2275 2280 2285 Tyr Gly Gln Gln Gly Ser Gly Ser Gly Gln Ser Pro Ser Arg Gly Arg 2290 2295 2300 His Gly Ser Gly Ser Gly His Ser Ser Ser Tyr Gly Gln His Gly Ser 2305 2310 2315 2320 Gly Ser Gly Trp Ser Ser Ser Ser Gly Arg His Gly Ser Gly Ser Gly 2325 2330 2335 Gln Ser Ser Gly Phe Gly His His Glu Ser Ser Ser Trp Gln Ser Ser 2340 2345 2350 Gly Tyr Thr Gln His Gly Ser Gly Ser Gly His Ser Ser Ser Tyr Glu 2355 2360 2365 Gln His Gly Ser Arg Ser Gly Gln Ser Ser Arg Gly Glu Arg His Gly 2370 2375 2380 Ser Ser Ser Gly Ser Ser Ser Ser Tyr Gly Gln His Gly Ser Gly Ser 2385 2390 2395 2400 Arg Gln Ser Leu Gly His Gly Gln His Gly Ser Gly Ser Gly Gln Ser 2405 2410 2415 Pro Ser Pro Ser Arg Gly Arg His Gly Ser Gly Ser Gly Gln Ser Ser 2420 2425 2430 Ser Tyr Ser Pro Tyr Gly Ser Gly Ser Gly Trp Ser Ser Ser Arg Gly 2435 2440 2445 Pro Tyr Glu Ser Gly Ser Gly His Ser Ser Gly Leu Gly His Arg Glu 2450 2455 2460 Ser Arg Ser Gly Gln Ser Ser Gly Tyr Gly Gln His Gly Ser Ser Ser 2465 2470 2475 2480 Gly His Ser Ser Thr His Gly Gln His Gly Ser Thr Ser Gly Gln Ser 2485 2490 2495 Ser Ser Cys Gly Gln His Gly Ala Ser Ser Gly Gln Ser Ser Ser His 2500 2505 2510 Gly Gln His Gly Ser Gly Ser Ser Gln Ser Ser Gly Tyr Gly Arg Gln 2515 2520 2525 Gly Ser Gly Ser Gly Gln Ser Pro Gly His Gly Gln Arg Gly Ser Gly 2530 2535 2540 Ser Arg Gln Ser Pro Ser Tyr Gly Arg His Gly Ser Gly Ser Gly Arg 2545 2550 2555 2560 Ser Ser Ser Ser Gly Gln His Gly Ser Gly Leu Gly Glu Ser Ser Gly 2565 2570 2575 Phe Gly His His Glu Ser Ser Ser Gly Gln Ser Ser Ser Tyr Ser Gln 2580 2585 2590 His Gly Ser Gly Ser Gly His Ser Ser Gly Tyr Gly Gln His Gly Ser 2595 2600 2605 Arg Ser Gly Gln Ser Ser Arg Gly Glu Arg His Gly Ser Ser Ser Gly 2610 2615 2620 Ser Ser Ser His Tyr Gly Gln His Gly Ser Gly Ser Arg Gln Ser Ser 2625 2630 2635 2640 Gly His Gly Arg Gln Gly Ser Gly Ser Gly Gln Ser Pro Ser Arg Gly 2645 2650 2655 Arg His Gly Ser Gly Leu Gly His Ser Ser Ser His Gly Gln His Gly 2660 2665 2670 Ser Gly Ser Gly Arg Ser Ser Ser Arg Gly Pro Tyr Glu Ser Arg Leu 2675 2680 2685 Gly His Ser Ser Val Phe Gly Gln His Glu Ser Gly Ser Gly His Ser 2690 2695 2700 Ser Ala Tyr Ser Gln His Gly Ser Gly Ser Gly His Phe Cys Ser Gln 2705 2710 2715 2720 Gly Gln His Gly Ser Thr Ser Gly Gln Ser Ser Thr Phe Asp Gln Glu 2725 2730 2735 Gly Ser Ser Thr Gly Gln Ser Ser Ser Tyr Gly His Arg Gly Ser Gly 2740 2745 2750 Ser Ser Gln Ser Ser Gly Tyr Gly Arg His Gly Ala Gly Ser Gly Gln 2755 2760 2765 Ser Leu Ser His Gly Arg His Gly Ser Gly Ser Gly Gln Ser Ser Ser 2770 2775 2780 Tyr Gly Gln His Gly Ser Gly Ser Gly Gln Ser Ser Gly Tyr Ser Gln 2785 2790 2795 2800 His Gly Ser Gly Ser Gly Gln Asp Gly Tyr Ser Tyr Cys Lys Gly Gly 2805 2810 2815 Ser Asn His Asp Gly Gly Ser Ser Gly Ser Tyr Phe Leu Ser Phe Pro 2820 2825 2830 Ser Ser Thr Ser Pro Tyr Glu Tyr Val Gln Glu Gln Arg Cys Tyr Phe 2835 2840 2845 Tyr Gln 2850 <210> 35 <211> 217 <212> PRT <213> Homo sapiens <400> 35 Ala Thr Arg Ser Pro Gly Val Val Ile Ser Asp Asp Glu Pro Gly Tyr 1 5 10 15 Asp Leu Asp Leu Phe Cys Ile Pro Asn His Tyr Ala Glu Asp Leu Glu 20 25 30 Arg Val Phe Ile Pro His Gly Leu Ile Met Asp Arg Thr Glu Arg Leu 35 40 45 Ala Arg Asp Val Met Lys Glu Met Gly Gly His His Ile Val Ala Leu 50 55 60 Cys Val Leu Lys Gly Gly Tyr Lys Phe Phe Ala Asp Leu Leu Asp Tyr 65 70 75 80 Ile Lys Ala Leu Asn Arg Asn Ser Asp Arg Ser Ile Pro Met Thr Val 85 90 95 Asp Phe Ile Arg Leu Lys Ser Tyr Cys Asn Asp Gln Ser Thr Gly Asp 100 105 110 Ile Lys Val Ile Gly Gly Asp Asp Leu Ser Thr Leu Thr Gly Lys Asn 115 120 125 Val Leu Ile Val Glu Asp Ile Ile Asp Thr Gly Lys Thr Met Gln Thr 130 135 140 Leu Leu Ser Leu Val Arg Gln Tyr Asn Pro Lys Met Val Lys Val Ala 145 150 155 160 Ser Leu Leu Val Lys Arg Thr Pro Arg Ser Val Gly Tyr Lys Pro Asp 165 170 175 Phe Val Gly Phe Glu Ile Pro Asp Lys Phe Val Val Gly Tyr Ala Leu 180 185 190 Asp Tyr Asn Glu Tyr Phe Arg Asp Leu Asn His Val Cys Val Ile Ser 195 200 205 Glu Thr Gly Lys Ala Lys Tyr Lys Ala 210 215 <210> 36 <211> 275 <212> PRT <213> Homo sapiens <400> 36 Met Ser Ser Phe Gly Tyr Arg Thr Leu Thr Val Ala Leu Phe Thr Leu 1 5 10 15 Ile Cys Cys Pro Gly Ser Asp Glu Lys Val Phe Glu Val His Val Arg 20 25 30 Pro Lys Lys Leu Ala Val Glu Pro Lys Gly Ser Leu Glu Val Asn Cys 35 40 45 Ser Thr Thr Cys Asn Gln Pro Glu Val Gly Gly Leu Glu Thr Ser Leu 50 55 60 Asp Lys Ile Leu Leu Asp Glu Gln Ala Gln Trp Lys His Tyr Leu Val 65 70 75 80 Ser Asn Ile Ser His Asp Thr Val Leu Gln Cys His Phe Thr Cys Ser 85 90 95 Gly Lys Gln Glu Ser Met Asn Ser Asn Val Ser Val Tyr Gln Pro Pro 100 105 110 Arg Gln Val Ile Leu Thr Leu Gln Pro Thr Leu Val Ala Val Gly Lys 115 120 125 Ser Phe Thr Ile Glu Cys Arg Val Pro Thr Val Glu Pro Leu Asp Ser 130 135 140 Leu Thr Leu Phe Leu Phe Arg Gly Asn Glu Thr Leu His Tyr Glu Thr 145 150 155 160 Phe Gly Lys Ala Ala Pro Ala Pro Gln Glu Ala Thr Ala Thr Phe Asn 165 170 175 Ser Thr Ala Asp Arg Glu Asp Gly His Arg Asn Phe Ser Cys Leu Ala 180 185 190 Val Leu Asp Leu Met Ser Arg Gly Gly Asn Ile Phe His Lys His Ser 195 200 205 Ala Pro Lys Met Leu Glu Ile Tyr Glu Pro Val Ser Asp Ser Gln Met 210 215 220 Val Ile Ile Val Thr Val Val Ser Val Leu Leu Ser Leu Phe Val Thr 225 230 235 240 Ser Val Leu Leu Cys Phe Ile Phe Gly Gln His Leu Arg Gln Gln Arg 245 250 255 Met Gly Thr Tyr Gly Val Arg Ala Ala Trp Arg Arg Leu Pro Gln Ala 260 265 270 Phe Arg Pro 275 <210> 37 <211> 322 <212> PRT <213> Homo sapiens <400> 37 Met Ser Ala Lys Ser Arg Thr Ile Gly Ile Ile Gly Ala Pro Phe Ser 1 5 10 15 Lys Gly Gln Pro Arg Gly Gly Val Glu Glu Gly Pro Thr Val Leu Arg 20 25 30 Lys Ala Gly Leu Leu Glu Lys Leu Lys Glu Gln Glu Cys Asp Val Lys 35 40 45 Asp Tyr Gly Asp Leu Pro Phe Ala Asp Ile Pro Asn Asp Ser Pro Phe 50 55 60 Gln Ile Val Lys Asn Pro Arg Ser Val Gly Lys Ala Ser Glu Gln Leu 65 70 75 80 Ala Gly Lys Val Ala Glu Val Lys Lys Asn Gly Arg Ile Ser Leu Val 85 90 95 Leu Gly Gly Asp His Ser Leu Ala Ile Gly Ser Ile Ser Gly His Ala 100 105 110 Arg Val His Pro Asp Leu Gly Val Ile Trp Val Asp Ala His Thr Asp 115 120 125 Ile Asn Thr Pro Leu Thr Thr Thr Ser Gly Asn Leu His Gly Gln Pro 130 135 140 Val Ser Phe Leu Leu Lys Glu Leu Lys Gly Lys Ile Pro Asp Val Pro 145 150 155 160 Gly Phe Ser Trp Val Thr Pro Cys Ile Ser Ala Lys Asp Ile Val Tyr 165 170 175 Ile Gly Leu Arg Asp Val Asp Pro Gly Glu His Tyr Ile Leu Lys Thr 180 185 190 Leu Gly Ile Lys Tyr Phe Ser Met Thr Glu Val Asp Arg Leu Gly Ile 195 200 205 Gly Lys Val Met Glu Glu Thr Leu Ser Tyr Leu Leu Gly Arg Lys Lys 210 215 220 Arg Pro Ile His Leu Ser Phe Asp Val Asp Gly Leu Asp Pro Ser Phe 225 230 235 240 Thr Pro Ala Thr Gly Thr Pro Val Val Gly Gly Leu Thr Tyr Arg Glu 245 250 255 Gly Leu Tyr Ile Thr Glu Glu Ile Tyr Lys Thr Gly Leu Leu Ser Gly 260 265 270 Leu Asp Ile Met Glu Val Asn Pro Ser Leu Gly Lys Thr Pro Glu Glu 275 280 285 Val Thr Arg Thr Val Asn Thr Ala Val Ala Ile Thr Leu Ala Cys Phe 290 295 300 Gly Leu Ala Arg Glu Gly Asn His Lys Pro Ile Asp Tyr Leu Asn Pro 305 310 315 320 Pro Lys <210> 38 <211> 1026 <212> PRT <213> Homo sapiens <400> 38 Met Arg Leu Pro Trp Glu Leu Leu Val Leu Gln Ser Phe Ile Leu Cys 1 5 10 15 Leu Ala Asp Asp Ser Thr Leu His Gly Pro Ile Phe Ile Gln Glu Pro 20 25 30 Ser Pro Val Met Phe Pro Leu Asp Ser Glu Glu Lys Lys Val Lys Leu 35 40 45 Asn Cys Glu Val Lys Gly Asn Pro Lys Pro His Ile Arg Trp Lys Leu 50 55 60 Asn Gly Thr Asp Val Asp Thr Gly Met Asp Phe Arg Tyr Ser Val Val 65 70 75 80 Glu Gly Ser Leu Leu Ile Asn Asn Pro Asn Lys Thr Gln Asp Ala Gly 85 90 95 Thr Tyr Gln Cys Thr Ala Thr Asn Ser Phe Gly Thr Ile Val Ser Arg 100 105 110 Glu Ala Lys Leu Gln Phe Ala Tyr Leu Asp Asn Phe Lys Thr Arg Thr 115 120 125 Arg Ser Thr Val Ser Val Arg Arg Gly Gln Gly Met Val Leu Leu Cys 130 135 140 Gly Pro Pro Pro His Ser Gly Glu Leu Ser Tyr Ala Trp Ile Phe Asn 145 150 155 160 Glu Tyr Pro Ser Tyr Gln Asp Asn Arg Arg Phe Val Ser Gln Glu Thr 165 170 175 Gly Asn Leu Tyr Ile Ala Lys Val Glu Lys Ser Asp Val Gly Asn Tyr 180 185 190 Thr Cys Val Val Thr Asn Thr Val Thr Asn His Lys Val Leu Gly Pro 195 200 205 Pro Thr Pro Leu Ile Leu Arg Asn Asp Gly Val Met Gly Glu Tyr Glu 210 215 220 Pro Lys Ile Glu Val Gln Phe Pro Glu Thr Val Pro Thr Ala Lys Gly 225 230 235 240 Ala Thr Val Lys Leu Glu Cys Phe Ala Leu Gly Asn Pro Val Pro Thr 245 250 255 Ile Ile Trp Arg Arg Ala Asp Gly Lys Pro Ile Ala Arg Lys Ala Arg 260 265 270 Arg His Lys Ser Asn Gly Ile Leu Glu Ile Pro Asn Phe Gln Gln Glu 275 280 285 Asp Ala Gly Leu Tyr Glu Cys Val Ala Glu Asn Ser Arg Gly Lys Asn 290 295 300 Val Ala Arg Gly Gln Leu Thr Phe Tyr Ala Gln Pro Asn Trp Ile Gln 305 310 315 320 Lys Ile Asn Asp Ile His Val Ala Met Glu Glu Asn Val Phe Trp Glu 325 330 335 Cys Lys Ala Asn Gly Arg Pro Lys Pro Thr Tyr Lys Trp Leu Lys Asn 340 345 350 Gly Glu Pro Leu Leu Thr Arg Asp Arg Ile Gln Ile Glu Gln Gly Thr 355 360 365 Leu Asn Ile Thr Ile Val Asn Leu Ser Asp Ala Gly Met Tyr Gln Cys 370 375 380 Leu Ala Glu Asn Lys His Gly Val Ile Phe Ser Asn Ala Glu Leu Ser 385 390 395 400 Val Ile Ala Val Gly Pro Asp Phe Ser Arg Thr Leu Leu Lys Arg Val 405 410 415 Thr Leu Val Lys Val Gly Gly Glu Val Val Ile Glu Cys Lys Pro Lys 420 425 430 Ala Ser Pro Lys Pro Val Tyr Thr Trp Lys Lys Gly Arg Asp Ile Leu 435 440 445 Lys Glu Asn Glu Arg Ile Thr Ile Ser Glu Asp Gly Asn Leu Arg Ile 450 455 460 Ile Asn Val Thr Lys Ser Asp Ala Gly Ser Tyr Thr Cys Ile Ala Thr 465 470 475 480 Asn His Phe Gly Thr Ala Ser Ser Thr Gly Asn Leu Val Val Lys Asp 485 490 495 Pro Thr Arg Val Met Val Pro Pro Ser Ser Met Asp Val Thr Val Gly 500 505 510 Glu Ser Ile Val Leu Pro Cys Gln Val Thr His Asp His Ser Leu Asp 515 520 525 Ile Val Phe Thr Trp Ser Phe Asn Gly His Leu Ile Asp Phe Asp Arg 530 535 540 Asp Gly Asp His Phe Glu Arg Val Gly Gly Gln Asp Ser Ala Gly Asp 545 550 555 560 Leu Met Ile Arg Asn Ile Gln Leu Lys His Ala Gly Lys Tyr Val Cys 565 570 575 Met Val Gln Thr Ser Val Asp Arg Leu Ser Ala Ala Ala Asp Leu Ile 580 585 590 Val Arg Gly Pro Pro Gly Pro Pro Glu Ala Val Thr Ile Asp Glu Ile 595 600 605 Thr Asp Thr Thr Ala Gln Leu Ser Trp Arg Pro Gly Pro Asp Asn His 610 615 620 Ser Pro Ile Thr Met Tyr Val Ile Gln Ala Arg Thr Pro Phe Ser Val 625 630 635 640 Gly Trp Gln Ala Val Ser Thr Val Pro Glu Leu Ile Asp Gly Lys Thr 645 650 655 Phe Thr Ala Thr Val Val Gly Leu Asn Pro Trp Val Glu Tyr Glu Phe 660 665 670 Arg Thr Val Ala Ala Asn Val Ile Gly Ile Gly Glu Pro Ser Arg Pro 675 680 685 Ser Glu Lys Arg Arg Thr Glu Glu Ala Leu Pro Glu Val Thr Pro Ala 690 695 700 Asn Val Ser Gly Gly Gly Gly Ser Lys Ser Glu Leu Val Ile Thr Trp 705 710 715 720 Glu Thr Val Pro Glu Glu Leu Gln Asn Gly Arg Gly Phe Gly Tyr Val 725 730 735 Val Ala Phe Arg Pro Tyr Gly Lys Met Ile Trp Met Leu Thr Val Leu 740 745 750 Ala Ser Ala Asp Ala Ser Arg Tyr Val Phe Arg Asn Glu Ser Val His 755 760 765 Pro Phe Ser Pro Phe Glu Val Lys Val Gly Val Phe Asn Asn Lys Gly 770 775 780 Glu Gly Pro Phe Ser Pro Thr Thr Val Val Tyr Ser Ala Glu Glu Glu 785 790 795 800 Pro Thr Lys Pro Pro Ala Ser Ile Phe Ala Arg Ser Leu Ser Ala Thr 805 810 815 Asp Ile Glu Val Phe Trp Ala Ser Pro Leu Glu Lys Asn Arg Gly Arg 820 825 830 Ile Gln Gly Tyr Glu Val Lys Tyr Trp Arg His Glu Asp Lys Glu Glu 835 840 845 Asn Ala Arg Lys Ile Arg Thr Val Gly Asn Gln Thr Ser Thr Lys Ile 850 855 860 Thr Asn Leu Lys Gly Ser Val Leu Tyr His Leu Ala Val Lys Ala Tyr 865 870 875 880 Asn Ser Ala Gly Thr Gly Pro Ser Ser Ala Thr Val Asn Val Thr Thr 885 890 895 Arg Lys Pro Pro Pro Ser Gln Pro Pro Gly Asn Ile Ile Trp Asn Ser 900 905 910 Ser Asp Ser Lys Ile Ile Leu Asn Trp Asp Gln Val Lys Ala Leu Asp 915 920 925 Asn Glu Ser Glu Val Lys Gly Tyr Lys Val Leu Tyr Arg Trp Asn Arg 930 935 940 Gln Ser Ser Thr Ser Val Ile Glu Thr Asn Lys Thr Ser Val Glu Leu 945 950 955 960 Ser Leu Pro Phe Asp Glu Asp Tyr Ile Ile Glu Ile Lys Pro Phe Ser 965 970 975 Asp Gly Gly Asp Gly Ser Ser Ser Glu Gln Ile Arg Ile Pro Lys Ile 980 985 990 Ser Asn Ala Tyr Ala Arg Gly Ser Gly Ala Ser Thr Ser Asn Ala Cys 995 1000 1005 Thr Leu Ser Ala Ile Ser Thr Ile Met Ile Ser Leu Thr Ala Arg Ser 1010 1015 1020 Ser Leu 1025 <210> 39 <211> 224 <212> PRT <213> Homo sapiens <400> 39 Met Glu Lys Leu Leu Cys Phe Leu Val Leu Thr Ser Leu Ser His Ala 1 5 10 15 Phe Gly Gln Thr Asp Met Ser Arg Lys Ala Phe Val Phe Pro Lys Glu 20 25 30 Ser Asp Thr Ser Tyr Val Ser Leu Lys Ala Pro Leu Thr Lys Pro Leu 35 40 45 Lys Ala Phe Thr Val Cys Leu His Phe Tyr Thr Glu Leu Ser Ser Thr 50 55 60 Arg Gly Tyr Ser Ile Phe Ser Tyr Ala Thr Lys Arg Gln Asp Asn Glu 65 70 75 80 Ile Leu Ile Phe Trp Ser Lys Asp Ile Gly Tyr Ser Phe Thr Val Gly 85 90 95 Gly Ser Glu Ile Leu Phe Glu Val Pro Glu Val Thr Val Ala Pro Val 100 105 110 His Ile Cys Thr Ser Trp Glu Ser Ala Ser Gly Ile Val Glu Phe Trp 115 120 125 Val Asp Gly Lys Pro Arg Val Arg Lys Ser Leu Lys Lys Gly Tyr Thr 130 135 140 Val Gly Ala Glu Ala Ser Ile Ile Leu Gly Gln Glu Gln Asp Ser Phe 145 150 155 160 Gly Gly Asn Phe Glu Gly Ser Gln Ser Leu Val Gly Asp Ile Gly Asn 165 170 175 Val Asn Met Trp Asp Phe Val Leu Ser Pro Asp Glu Ile Asn Thr Ile 180 185 190 Tyr Leu Gly Gly Pro Phe Ser Pro Asn Val Leu Asn Trp Arg Ala Leu 195 200 205 Lys Tyr Glu Val Gln Gly Glu Val Phe Thr Lys Pro Gln Leu Trp Pro 210 215 220 <210> 40 <211> 299 <212> PRT <213> Homo sapiens <400> 40 Met Asp Leu Leu Trp Ile Leu Pro Ser Leu Trp Leu Leu Leu Leu Gly 1 5 10 15 Gly Pro Ala Cys Leu Lys Thr Gln Glu His Pro Ser Cys Pro Gly Pro 20 25 30 Arg Glu Leu Glu Ala Ser Lys Val Val Leu Leu Pro Ser Cys Pro Gly 35 40 45 Ala Pro Gly Ser Pro Gly Glu Lys Gly Ala Pro Gly Pro Gln Gly Pro 50 55 60 Pro Gly Pro Pro Gly Lys Met Gly Pro Lys Gly Glu Pro Gly Asp Pro 65 70 75 80 Val Asn Leu Leu Arg Cys Gln Glu Gly Pro Arg Asn Cys Arg Glu Leu 85 90 95 Leu Ser Gln Gly Ala Thr Leu Ser Gly Trp Tyr His Leu Cys Leu Pro 100 105 110 Glu Gly Arg Ala Leu Pro Val Phe Cys Asp Met Asp Thr Glu Gly Gly 115 120 125 Gly Trp Leu Val Phe Gln Arg Arg Gln Asp Gly Ser Val Asp Phe Phe 130 135 140 Arg Ser Trp Ser Ser Tyr Arg Ala Gly Phe Gly Asn Gln Glu Ser Glu 145 150 155 160 Phe Trp Leu Gly Asn Glu Asn Leu His Gln Leu Thr Leu Gln Gly Asn 165 170 175 Trp Glu Leu Arg Val Glu Leu Glu Asp Phe Asn Gly Asn Arg Thr Phe 180 185 190 Ala His Tyr Ala Thr Phe Arg Leu Leu Gly Glu Val Asp His Tyr Gln 195 200 205 Leu Ala Leu Gly Lys Phe Ser Glu Gly Thr Ala Gly Asp Ser Leu Ser 210 215 220 Leu His Ser Gly Arg Pro Phe Thr Thr Tyr Asp Ala Asp His Asp Ser 225 230 235 240 Ser Asn Ser Asn Cys Ala Val Ile Val His Gly Ala Trp Trp Tyr Ala 245 250 255 Ser Cys Tyr Arg Ser Asn Leu Asn Gly Arg Tyr Ala Val Ser Glu Ala 260 265 270 Ala Ala His Lys Tyr Gly Ile Asp Trp Ala Ser Gly Arg Gly Val Gly 275 280 285 His Pro Tyr Arg Arg Val Arg Met Met Leu Arg 290 295 <210> 41 <211> 686 <212> PRT <213> Homo sapiens <400> 41 Met Arg Leu Leu Thr Leu Leu Gly Leu Leu Cys Gly Ser Val Ala Thr 1 5 10 15 Pro Leu Gly Pro Lys Trp Pro Glu Pro Val Phe Gly Arg Leu Ala Ser 20 25 30 Pro Gly Phe Pro Gly Glu Tyr Ala Asn Asp Gln Glu Arg Arg Trp Thr 35 40 45 Leu Thr Ala Pro Pro Gly Tyr Arg Leu Arg Leu Tyr Phe Thr His Phe 50 55 60 Asp Leu Glu Leu Ser His Leu Cys Glu Tyr Asp Phe Val Lys Leu Ser 65 70 75 80 Ser Gly Ala Lys Val Leu Ala Thr Leu Cys Gly Gln Glu Ser Thr Asp 85 90 95 Thr Glu Arg Ala Pro Gly Lys Asp Thr Phe Tyr Ser Leu Gly Ser Ser 100 105 110 Leu Asp Ile Thr Phe Arg Ser Asp Tyr Ser Asn Glu Lys Pro Phe Thr 115 120 125 Gly Phe Glu Ala Phe Tyr Ala Ala Glu Asp Ile Asp Glu Cys Gln Val 130 135 140 Ala Pro Gly Glu Ala Pro Thr Cys Asp His His Cys His Asn His Leu 145 150 155 160 Gly Gly Phe Tyr Cys Ser Cys Arg Ala Gly Tyr Val Leu His Arg Asn 165 170 175 Lys Arg Thr Cys Ser Ala Leu Cys Ser Gly Gln Val Phe Thr Gln Arg 180 185 190 Ser Gly Glu Leu Ser Ser Pro Glu Tyr Pro Arg Pro Tyr Pro Lys Leu 195 200 205 Ser Ser Cys Thr Tyr Ser Ile Ser Leu Glu Glu Gly Phe Ser Val Ile 210 215 220 Leu Asp Phe Val Glu Ser Phe Asp Val Glu Thr His Pro Glu Thr Leu 225 230 235 240 Cys Pro Tyr Asp Phe Leu Lys Ile Gln Thr Asp Arg Glu Glu His Gly 245 250 255 Pro Phe Cys Gly Lys Thr Leu Pro His Arg Ile Glu Thr Lys Ser Asn 260 265 270 Thr Val Thr Ile Thr Phe Val Thr Asp Glu Ser Gly Asp His Thr Gly 275 280 285 Trp Lys Ile His Tyr Thr Ser Thr Ala His Ala Cys Pro Tyr Pro Met 290 295 300 Ala Pro Pro Asn Gly His Val Ser Pro Val Gln Ala Lys Tyr Ile Leu 305 310 315 320 Lys Asp Ser Phe Ser Ile Phe Cys Glu Thr Gly Tyr Glu Leu Leu Gln 325 330 335 Gly His Leu Pro Leu Lys Ser Phe Thr Ala Val Cys Gln Lys Asp Gly 340 345 350 Ser Trp Asp Arg Pro Met Pro Ala Cys Ser Ile Val Asp Cys Gly Pro 355 360 365 Pro Asp Tyr Leu Pro Ser Gly Arg Val Glu Tyr Ile Thr Gly Pro Gly 370 375 380 Val Thr Thr Tyr Lys Ala Val Ile Gln Tyr Ser Cys Glu Glu Thr Phe 385 390 395 400 Tyr Thr Met Lys Val Asn Asp Gly Lys Tyr Val Cys Glu Ala Asp Gly 405 410 415 Phe Trp Thr Ser Ser Lys Gly Glu Lys Ser Leu Pro Val Cys Glu Pro 420 425 430 Val Cys Gly Leu Ser Ala Arg Thr Thr Gly Gly Arg Ile Tyr Gly Gly 435 440 445 Gln Lys Ala Lys Pro Gly Asp Phe Pro Trp Gln Val Leu Ile Leu Gly 450 455 460 Gly Thr Thr Ala Ala Gly Ala Leu Leu Tyr Asp Asn Trp Val Leu Thr 465 470 475 480 Ala Ala His Ala Val Tyr Glu Gln Lys His Asp Ala Ser Ala Leu Asp 485 490 495 Ile Arg Met Gly Thr Leu Lys Arg Leu Ser Pro His Tyr Thr Gln Ala 500 505 510 Trp Ser Glu Ala Val Phe Ile His Glu Gly Tyr Thr His Asp Ala Gly 515 520 525 Phe Asp Asn Asp Ile Ala Leu Ile Lys Leu Asn Asn Lys Val Val Ile 530 535 540 Asn Ser Asn Ile Thr Pro Ile Cys Leu Pro Arg Lys Glu Ala Glu Ser 545 550 555 560 Phe Met Arg Thr Asp Asp Ile Gly Thr Ala Ser Gly Trp Gly Leu Thr 565 570 575 Gln Arg Gly Phe Leu Ala Arg Asn Leu Met Tyr Val Asp Ile Pro Ile 580 585 590 Val Asp His Gln Lys Cys Thr Ala Ala Tyr Glu Lys Pro Pro Tyr Pro 595 600 605 Arg Gly Ser Val Thr Ala Asn Met Leu Cys Ala Gly Leu Glu Ser Gly 610 615 620 Gly Lys Asp Ser Cys Arg Gly Asp Ser Gly Gly Ala Leu Val Phe Leu 625 630 635 640 Asp Ser Glu Thr Glu Arg Trp Phe Val Gly Gly Ile Val Ser Trp Gly 645 650 655 Ser Met Asn Cys Gly Glu Ala Gly Gln Tyr Gly Val Tyr Thr Lys Val 660 665 670 Ile Asn Tyr Ile Pro Trp Ile Glu Asn Ile Ile Ser Asp Phe 675 680 685 <210> 42 <211> 2386 <212> PRT <213> Homo sapiens <400> 42 Met Val Val Tyr Gly Gly Asn Val His Thr His Tyr Gln Glu Glu Lys 1 5 10 15 Cys Tyr Glu Asp Gly Ile Phe Phe Tyr His Leu Gly Cys His Gln Trp 20 25 30 Val Ser Gly Ala Glu Leu Ala Pro Pro Gly Thr Pro Glu Gly Arg Ala 35 40 45 Ala Pro Pro Ser Gly Arg Tyr Ser His Val Ala Ala Val Leu Gly Gly 50 55 60 Ser Val Leu Leu Val Ala Gly Gly Tyr Ser Gly Arg Pro Arg Gly Asp 65 70 75 80 Leu Met Ala Tyr Lys Val Pro Pro Phe Val Phe Gln Ala Pro Ala Pro 85 90 95 Asp Tyr His Leu Asp Tyr Cys Ser Met Tyr Thr Asp His Ser Val Cys 100 105 110 Ser Arg Asp Pro Glu Cys Ser Trp Cys Gln Gly Ala Cys Gln Ala Ala 115 120 125 Pro Pro Pro Gly Thr Pro Leu Gly Ala Cys Pro Ala Ala Ser Cys Leu 130 135 140 Gly Leu Gly Arg Leu Leu Gly Asp Cys Gln Ala Cys Leu Ala Phe Ser 145 150 155 160 Ser Pro Thr Ala Pro Pro Arg Gly Pro Gly Thr Leu Gly Trp Cys Val 165 170 175 His Asn Glu Ser Cys Leu Pro Arg Pro Glu Gln Ala Arg Cys Arg Gly 180 185 190 Glu Gln Ile Ser Gly Thr Val Gly Trp Trp Gly Pro Ala Pro Val Phe 195 200 205 Val Thr Ser Leu Glu Ala Cys Val Thr Gln Ser Phe Leu Pro Gly Leu 210 215 220 His Leu Leu Thr Phe Gln Gln Pro Pro Asn Thr Ser Gln Pro Asp Lys 225 230 235 240 Val Ser Ile Val Arg Ser Thr Thr Ile Thr Leu Thr Pro Ser Ala Glu 245 250 255 Thr Asp Val Ser Leu Val Tyr Arg Gly Phe Ile Tyr Pro Met Leu Pro 260 265 270 Gly Gly Pro Gly Gly Pro Gly Ala Glu Asp Val Ala Val Trp Thr Arg 275 280 285 Ala Gln Arg Leu His Val Leu Ala Arg Met Ala Arg Gly Pro Asp Thr 290 295 300 Glu Asn Met Glu Glu Val Gly Arg Trp Val Ala His Gln Glu Lys Glu 305 310 315 320 Thr Arg Arg Leu Gln Arg Pro Gly Ser Ala Arg Leu Phe Pro Leu Pro 325 330 335 Gly Arg Asp His Lys Tyr Ala Val Glu Ile Gln Gly Gln Leu Asn Gly 340 345 350 Ser Ala Gly Pro Gly His Ser Glu Leu Thr Leu Leu Trp Asp Arg Thr 355 360 365 Gly Val Pro Gly Gly Ser Glu Ile Ser Phe Phe Phe Leu Glu Pro Tyr 370 375 380 Arg Ser Ser Ser Cys Thr Ser Tyr Ser Ser Cys Leu Gly Cys Leu Ala 385 390 395 400 Asp Gln Gly Cys Gly Trp Cys Leu Thr Ser Ala Thr Cys His Leu Arg 405 410 415 Gln Gly Gly Ala His Cys Gly Asp Asp Gly Ala Gly Gly Ser Leu Leu 420 425 430 Val Leu Val Pro Thr Leu Cys Pro Leu Cys Glu Glu His Arg Asp Cys 435 440 445 His Ala Cys Thr Gln Asp Pro Phe Cys Glu Trp His Gln Ser Thr Ser 450 455 460 Arg Lys Gly Asp Ala Ala Cys Ser Arg Arg Gly Arg Gly Arg Gly Ala 465 470 475 480 Leu Lys Ser Pro Glu Glu Cys Pro Pro Leu Cys Ser Gln Arg Leu Thr 485 490 495 Cys Glu Asp Cys Leu Ala Asn Ser Ser Gln Cys Ala Trp Cys Gln Ser 500 505 510 Thr His Thr Cys Phe Leu Phe Ala Ala Tyr Leu Ala Arg Tyr Pro His 515 520 525 Gly Gly Cys Arg Gly Trp Asp Asp Ser Val His Ser Glu Pro Arg Cys 530 535 540 Arg Ser Cys Asp Gly Phe Leu Thr Cys His Glu Cys Leu Gln Ser His 545 550 555 560 Glu Cys Gly Trp Cys Gly Asn Glu Asp Asn Pro Thr Leu Gly Arg Cys 565 570 575 Leu Gln Gly Asp Phe Ser Gly Pro Leu Gly Gly Gly Asn Cys Ser Leu 580 585 590 Trp Val Gly Glu Gly Leu Gly Leu Pro Val Ala Leu Pro Ala Arg Trp 595 600 605 Ala Tyr Ala Arg Cys Pro Asp Val Asp Glu Cys Arg Leu Gly Leu Ala 610 615 620 Arg Cys His Pro Arg Ala Thr Cys Leu Asn Thr Pro Leu Ser Tyr Glu 625 630 635 640 Cys His Cys Gln Arg Gly Tyr Gln Gly Asp Gly Ile Ser His Cys Asn 645 650 655 Arg Thr Cys Leu Glu Asp Cys Gly His Gly Val Cys Ser Gly Pro Pro 660 665 670 Asp Phe Thr Cys Val Cys Asp Leu Gly Trp Thr Ser Asp Leu Pro Pro 675 680 685 Pro Thr Pro Ala Pro Gly Pro Pro Ala Pro Arg Cys Ser Arg Asp Cys 690 695 700 Gly Cys Ser Phe His Ser His Cys Arg Lys Arg Gly Pro Gly Phe Cys 705 710 715 720 Asp Glu Cys Gln Asp Trp Thr Trp Gly Glu His Cys Glu Arg Cys Arg 725 730 735 Pro Gly Ser Phe Gly Asn Ala Thr Gly Ser Arg Gly Cys Arg Pro Cys 740 745 750 Gln Cys Asn Gly His Gly Asp Pro Arg Arg Gly His Cys Asp Asn Leu 755 760 765 Ser Gly Leu Cys Phe Cys Gln Asp His Thr Glu Gly Ala His Cys Gln 770 775 780 Leu Cys Ser Pro Gly Tyr Tyr Gly Asp Pro Arg Ala Gly Gly Ser Cys 785 790 795 800 Phe Arg Glu Cys Gly Gly Arg Ala Leu Leu Thr Asn Val Ser Ser Val 805 810 815 Ala Leu Gly Ser Arg Arg Val Gly Gly Leu Leu Pro Pro Gly Gly Gly 820 825 830 Ala Ala Arg Ala Gly Pro Gly Leu Ser Tyr Cys Val Trp Val Val Ser 835 840 845 Ala Thr Glu Glu Leu Gln Pro Cys Ala Pro Gly Thr Leu Cys Pro Pro 850 855 860 Leu Thr Leu Thr Phe Ser Pro Asp Ser Ser Thr Pro Cys Thr Leu Ser 865 870 875 880 Tyr Val Leu Ala Phe Asp Gly Phe Pro Arg Phe Leu Asp Thr Gly Val 885 890 895 Val Gln Ser Asp Arg Ser Leu Ile Ala Ala Phe Cys Gly Gln Arg Arg 900 905 910 Asp Arg Pro Leu Thr Val Gln Ala Leu Ser Gly Leu Leu Val Leu His 915 920 925 Trp Glu Ala Asn Gly Ser Ser Ser Trp Gly Phe Asn Ala Ser Val Gly 930 935 940 Ser Ala Arg Cys Gly Ser Gly Gly Pro Gly Ser Cys Pro Val Pro Gln 945 950 955 960 Glu Cys Val Pro Gln Asp Gly Ala Ala Gly Ala Gly Leu Cys Arg Cys 965 970 975 Pro Gln Gly Trp Ala Gly Pro His Cys Arg Met Ala Leu Cys Pro Glu 980 985 990 Asn Cys Asn Ala His Thr Gly Ala Gly Thr Cys Asn Gln Ser Leu Gly 995 1000 1005 Val Cys Ile Cys Ala Glu Gly Phe Gly Gly Pro Asp Cys Ala Thr Lys 1010 1015 1020 Leu Asp Gly Gly Gln Leu Val Trp Glu Thr Leu Met Asp Ser Arg Leu 1025 1030 1035 1040 Ser Ala Asp Thr Ala Ser Arg Phe Leu His Arg Leu Gly His Thr Met 1045 1050 1055 Val Asp Gly Pro Asp Ala Thr Leu Trp Met Phe Gly Gly Leu Gly Leu 1060 1065 1070 Pro Gln Gly Leu Leu Gly Asn Leu Tyr Arg Tyr Ser Val Ser Glu Arg 1075 1080 1085 Arg Trp Thr Gln Met Leu Ala Gly Ala Glu Asp Gly Gly Pro Gly Pro 1090 1095 1100 Ser Pro Arg Ser Phe His Ala Ala Ala Tyr Val Pro Ala Gly Arg Gly 1105 1110 1115 1120 Ala Met Tyr Leu Leu Gly Gly Leu Thr Ala Gly Gly Val Thr Arg Asp 1125 1130 1135 Phe Trp Val Leu Asn Leu Thr Thr Leu Gln Trp Arg Gln Glu Lys Ala 1140 1145 1150 Pro Gln Thr Val Glu Leu Pro Ala Val Ala Gly His Thr Leu Thr Ala 1155 1160 1165 Arg Arg Gly Leu Ser Leu Leu Leu Val Gly Gly Tyr Ser Pro Glu Asn 1170 1175 1180 Gly Phe Asn Gln Gln Leu Leu Glu Tyr Gln Leu Ala Thr Gly Thr Trp 1185 1190 1195 1200 Val Ser Gly Ala Gln Ser Gly Thr Pro Pro Thr Gly Leu Tyr Gly His 1205 1210 1215 Ser Ala Val Tyr His Glu Ala Thr Asp Ser Leu Tyr Val Phe Gly Gly 1220 1225 1230 Phe Arg Phe His Val Glu Leu Ala Ala Pro Ser Pro Glu Leu Tyr Ser 1235 1240 1245 Leu His Cys Pro Asp Arg Thr Trp Ser Leu Leu Ala Pro Ser Gln Gly 1250 1255 1260 Ala Lys Arg Asp Arg Met Arg Asn Val Arg Gly Ser Ser Arg Gly Leu 1265 1270 1275 1280 Gly Gln Val Pro Gly Glu Gln Pro Gly Ser Trp Gly Phe Arg Glu Val 1285 1290 1295 Arg Lys Lys Met Ala Leu Trp Ala Ala Leu Ala Gly Thr Gly Gly Phe 1300 1305 1310 Leu Glu Glu Ile Ser Pro His Leu Lys Glu Pro Arg Pro Arg Leu Phe 1315 1320 1325 His Ala Ser Ala Leu Leu Gly Asp Thr Met Val Val Leu Gly Gly Arg 1330 1335 1340 Ser Asp Pro Asp Glu Phe Ser Ser Asp Val Leu Leu Tyr Gln Val Asn 1345 1350 1355 1360 Cys Asn Ala Trp Leu Leu Pro Asp Leu Thr Arg Ser Ala Ser Val Gly 1365 1370 1375 Pro Pro Met Glu Glu Ser Val Ala His Ala Val Ala Ala Val Gly Ser 1380 1385 1390 Arg Leu Tyr Ile Ser Gly Gly Phe Gly Gly Val Ala Leu Gly Arg Leu 1395 1400 1405 Leu Ala Leu Thr Leu Pro Pro Asp Pro Cys Arg Leu Leu Ser Ser Pro 1410 1415 1420 Glu Ala Cys Asn Gln Ser Gly Ala Cys Thr Trp Cys His Gly Ala Cys 1425 1430 1435 1440 Leu Ser Gly Asp Gln Ala His Arg Leu Gly Cys Gly Gly Ser Pro Cys 1445 1450 1455 Ser Pro Met Pro Arg Ser Pro Glu Glu Cys Arg Arg Leu Arg Thr Cys 1460 1465 1470 Ser Glu Cys Leu Ala Arg His Pro Arg Thr Leu Gln Pro Gly Asp Gly 1475 1480 1485 Glu Ala Ser Thr Pro Arg Cys Lys Trp Cys Thr Asn Cys Pro Glu Gly 1490 1495 1500 Ala Cys Ile Gly Arg Asn Gly Ser Cys Thr Ser Glu Asn Asp Cys Arg 1505 1510 1515 1520 Ile Asn Gln Arg Glu Val Phe Trp Ala Gly Asn Cys Ser Glu Ala Ala 1525 1530 1535 Cys Gly Ala Ala Asp Cys Glu Gln Cys Thr Arg Glu Gly Lys Cys Met 1540 1545 1550 Trp Thr Arg Gln Phe Lys Arg Thr Gly Glu Thr Arg Arg Ile Leu Ser 1555 1560 1565 Val Gln Pro Thr Tyr Asp Trp Thr Cys Phe Ser His Ser Leu Leu Asn 1570 1575 1580 Val Ser Pro Met Pro Val Glu Ser Ser Pro Pro Leu Pro Cys Pro Thr 1585 1590 1595 1600 Pro Cys His Leu Leu Pro Asn Cys Thr Ser Cys Leu Asp Ser Lys Gly 1605 1610 1615 Ala Asp Gly Gly Trp Gln His Cys Val Trp Ser Ser Ser Leu Gln Gln 1620 1625 1630 Cys Leu Ser Pro Ser Tyr Leu Pro Leu Arg Cys Met Ala Gly Gly Cys 1635 1640 1645 Gly Arg Leu Leu Arg Gly Pro Glu Ser Cys Ser Leu Gly Cys Ala Gln 1650 1655 1660 Ala Thr Gln Cys Ala Leu Cys Leu Arg Arg Pro His Cys Gly Trp Cys 1665 1670 1675 1680 Ala Trp Gly Gly Gln Asp Gly Gly Gly Arg Cys Met Glu Gly Gly Leu 1685 1690 1695 Ser Gly Pro Arg Asp Gly Leu Thr Cys Gly Arg Pro Gly Ala Ser Trp 1700 1705 1710 Ala Phe Leu Ser Cys Pro Pro Glu Asp Glu Cys Ala Asn Gly His His 1715 1720 1725 Asp Cys Asn Glu Thr Gln Asn Cys His Asp Gln Pro His Gly Tyr Glu 1730 1735 1740 Cys Ser Cys Lys Thr Gly Tyr Thr Met Asp Asn Met Thr Gly Leu Cys 1745 1750 1755 1760 Arg Pro Val Cys Ala Gln Gly Cys Val Asn Gly Ser Cys Val Glu Pro 1765 1770 1775 Asp His Cys Arg Cys His Phe Gly Phe Val Gly Arg Asn Cys Ser Thr 1780 1785 1790 Glu Cys Arg Cys Asn Arg His Ser Glu Cys Ala Gly Val Gly Ala Arg 1795 1800 1805 Asp His Cys Leu Leu Cys Arg Asn His Thr Lys Gly Ser His Cys Glu 1810 1815 1820 Gln Cys Leu Pro Leu Phe Val Gly Ser Ala Val Gly Gly Gly Thr Cys 1825 1830 1835 1840 Arg Pro Cys His Ala Phe Cys Arg Gly Asn Ser His Ile Cys Ile Ser 1845 1850 1855 Arg Lys Glu Leu Gln Met Ser Lys Gly Glu Pro Lys Lys Tyr Ser Leu 1860 1865 1870 Asp Pro Glu Glu Ile Glu Asn Trp Val Thr Glu Gly Pro Ser Glu Asp 1875 1880 1885 Glu Ala Val Cys Val Asn Cys Gln Asn Asn Ser Tyr Gly Glu Lys Cys 1890 1895 1900 Glu Ser Cys Leu Gln Gly Tyr Phe Leu Leu Asp Gly Lys Cys Thr Lys 1905 1910 1915 1920 Cys Gln Cys Asn Gly His Ala Asp Thr Cys Asn Glu Gln Asp Gly Thr 1925 1930 1935 Gly Cys Pro Cys Gln Asn Asn Thr Glu Thr Gly Thr Cys Gln Gly Ser 1940 1945 1950 Ser Pro Ser Asp Arg Arg Asp Cys Tyr Lys Tyr Gln Cys Ala Lys Cys 1955 1960 1965 Arg Glu Ser Phe His Gly Ser Pro Leu Gly Gly Gln Gln Cys Tyr Arg 1970 1975 1980 Leu Ile Ser Val Glu Gln Glu Cys Cys Leu Asp Pro Thr Ser Gln Thr 1985 1990 1995 2000 Asn Cys Phe His Glu Pro Lys Arg Arg Ala Leu Gly Pro Gly Arg Thr 2005 2010 2015 Val Leu Phe Gly Val Gln Pro Lys Phe Thr Asn Val Asp Ile Arg Leu 2020 2025 2030 Thr Leu Asp Val Thr Phe Gly Ala Val Asp Leu Tyr Val Ser Thr Ser 2035 2040 2045 Tyr Asp Thr Phe Val Val Arg Val Ala Pro Asp Thr Gly Val His Thr 2050 2055 2060 Val His Ile Gln Pro Pro Pro Ala Pro Pro Pro Pro Pro Pro Pro Ala 2065 2070 2075 2080 Asp Gly Gly Pro Arg Gly Ala Gly Asp Pro Gly Gly Ala Gly Ala Ser 2085 2090 2095 Ser Gly Pro Gly Ala Pro Ala Glu Pro Arg Val Arg Glu Val Trp Pro 2100 2105 2110 Arg Gly Leu Ile Thr Tyr Val Thr Val Thr Glu Pro Ser Ala Val Leu 2115 2120 2125 Val Val Arg Gly Val Arg Asp Arg Leu Val Ile Thr Tyr Pro His Glu 2130 2135 2140 His His Ala Leu Lys Ser Ser Arg Phe Tyr Leu Leu Leu Leu Gly Val 2145 2150 2155 2160 Gly Asp Pro Ser Gly Pro Gly Ala Asn Gly Ser Ala Asp Ser Gln Gly 2165 2170 2175 Leu Leu Phe Phe Arg Gln Asp Gln Ala His Ile Asp Leu Phe Val Phe 2180 2185 2190 Phe Ser Val Phe Phe Ser Cys Phe Phe Leu Phe Leu Ser Leu Cys Val 2195 2200 2205 Leu Leu Trp Lys Ala Lys Gln Ala Leu Asp Gln Arg Gln Glu Gln Arg 2210 2215 2220 Arg His Leu Gln Glu Met Thr Lys Met Ala Ser Arg Pro Phe Ala Lys 2225 2230 2235 2240 Val Thr Val Cys Phe Pro Pro Asp Pro Thr Ala Pro Ala Ser Ala Trp 2245 2250 2255 Lys Pro Ala Gly Leu Pro Pro Pro Ala Phe Arg Arg Ser Glu Pro Phe 2260 2265 2270 Leu Ala Pro Leu Leu Leu Thr Gly Ala Gly Gly Pro Trp Gly Pro Met 2275 2280 2285 Gly Gly Gly Cys Cys Pro Pro Ala Ile Pro Ala Thr Thr Ala Gly Leu 2290 2295 2300 Arg Ala Gly Pro Ile Thr Leu Glu Pro Thr Glu Asp Gly Met Ala Gly 2305 2310 2315 2320 Val Ala Thr Leu Leu Leu Gln Leu Pro Gly Gly Pro His Ala Pro Asn 2325 2330 2335 Gly Ala Cys Leu Gly Ser Ala Leu Val Thr Leu Arg His Arg Leu His 2340 2345 2350 Glu Tyr Cys Gly Gly Gly Gly Gly Ala Gly Gly Ser Gly His Gly Thr 2355 2360 2365 Gly Ala Gly Arg Lys Gly Leu Leu Ser Gln Asp Asn Leu Thr Ser Met 2370 2375 2380 Ser Leu 2385 <210> 43 <211> 840 <212> PRT <213> Homo sapiens <400> 43 Met Ser Ala Phe Arg Leu Trp Pro Gly Leu Leu Ile Met Leu Gly Ser 1 5 10 15 Leu Cys His Arg Gly Ser Pro Cys Gly Leu Ser Thr His Val Glu Ile 20 25 30 Gly His Arg Ala Leu Glu Phe Leu Gln Leu His Asn Gly Arg Val Asn 35 40 45 Tyr Arg Glu Leu Leu Leu Glu His Gln Asp Ala Tyr Gln Ala Gly Ile 50 55 60 Val Phe Pro Asp Cys Phe Tyr Pro Ser Ile Cys Lys Gly Gly Lys Phe 65 70 75 80 His Asp Val Ser Glu Ser Thr His Trp Thr Pro Phe Leu Asn Ala Ser 85 90 95 Val His Tyr Ile Arg Glu Asn Tyr Pro Leu Pro Trp Glu Lys Asp Thr 100 105 110 Glu Lys Leu Val Ala Phe Leu Phe Gly Ile Thr Ser His Met Ala Ala 115 120 125 Asp Val Ser Trp His Ser Leu Gly Leu Glu Gln Gly Phe Leu Arg Thr 130 135 140 Met Gly Ala Ile Asp Phe His Gly Ser Tyr Ser Glu Ala His Ser Ala 145 150 155 160 Gly Asp Phe Gly Gly Asp Val Leu Ser Gln Phe Glu Phe Asn Phe Asn 165 170 175 Tyr Leu Ala Arg Arg Trp Tyr Val Pro Val Lys Asp Leu Leu Gly Ile 180 185 190 Tyr Glu Lys Leu Tyr Gly Arg Lys Val Ile Thr Glu Asn Val Ile Val 195 200 205 Asp Cys Ser His Ile Gln Phe Leu Glu Met Tyr Gly Glu Met Leu Ala 210 215 220 Val Ser Lys Leu Tyr Pro Thr Tyr Ser Thr Lys Ser Pro Phe Leu Val 225 230 235 240 Glu Gln Phe Gln Glu Tyr Phe Leu Gly Gly Leu Asp Asp Met Ala Phe 245 250 255 Trp Ser Thr Asn Ile Tyr His Leu Thr Ile Phe Met Leu Glu Asn Gly 260 265 270 Thr Ser Asp Cys Asn Leu Pro Glu Asn Pro Leu Phe Ile Ala Cys Gly 275 280 285 Gly Gln Gln Asn His Thr Gln Gly Ser Lys Met Gln Lys Asn Asp Phe 290 295 300 His Arg Asn Leu Thr Thr Ser Leu Thr Glu Ser Val Asp Arg Asn Ile 305 310 315 320 Asn Tyr Thr Glu Arg Gly Val Phe Phe Ser Val Asn Ser Trp Thr Pro 325 330 335 Asp Ser Met Ser Phe Ile Tyr Lys Ala Leu Glu Arg Asn Ile Arg Thr 340 345 350 Met Phe Ile Gly Gly Ser Gln Leu Ser Gln Lys His Val Ser Ser Pro 355 360 365 Leu Ala Ser Tyr Phe Leu Ser Phe Pro Tyr Ala Arg Leu Gly Trp Ala 370 375 380 Met Thr Ser Ala Asp Leu Asn Gln Asp Gly His Gly Asp Leu Val Val 385 390 395 400 Gly Ala Pro Gly Tyr Ser Arg Pro Gly His Ile His Ile Gly Arg Val 405 410 415 Tyr Leu Ile Tyr Gly Asn Asp Leu Gly Leu Pro Pro Val Asp Leu Asp 420 425 430 Leu Asp Lys Glu Ala His Arg Ile Leu Glu Gly Phe Gln Pro Ser Gly 435 440 445 Arg Phe Gly Ser Ala Leu Ala Val Leu Asp Phe Asn Val Asp Gly Val 450 455 460 Pro Asp Leu Ala Val Gly Ala Pro Ser Val Gly Ser Glu Gln Leu Thr 465 470 475 480 Tyr Lys Gly Ala Val Tyr Val Tyr Phe Gly Ser Lys Gln Gly Gly Met 485 490 495 Ser Ser Ser Pro Asn Ile Thr Ile Ser Cys Gln Asp Ile Tyr Cys Asn 500 505 510 Leu Gly Trp Thr Leu Leu Ala Ala Asp Val Asn Gly Asp Ser Glu Pro 515 520 525 Asp Leu Val Ile Gly Ser Pro Phe Ala Pro Gly Gly Gly Lys Gln Lys 530 535 540 Gly Ile Val Ala Ala Phe Tyr Ser Gly Pro Ser Leu Ser Asp Lys Glu 545 550 555 560 Lys Leu Asn Val Glu Ala Ala Asn Trp Thr Val Arg Gly Glu Glu Asp 565 570 575 Phe Ser Trp Phe Gly Tyr Ser Leu His Gly Val Thr Val Asp Asn Arg 580 585 590 Thr Leu Leu Leu Val Gly Ser Pro Thr Trp Lys Asn Ala Ser Arg Leu 595 600 605 Gly His Leu Leu His Ile Arg Asp Glu Lys Lys Ser Leu Gly Arg Val 610 615 620 Tyr Gly Tyr Phe Pro Pro Asn Gly Gln Ser Trp Phe Thr Ile Ser Gly 625 630 635 640 Asp Lys Ala Met Gly Lys Leu Gly Thr Ser Leu Ser Ser Gly His Val 645 650 655 Leu Met Asn Gly Thr Leu Lys Gln Val Leu Leu Val Gly Ala Pro Thr 660 665 670 Tyr Asp Asp Val Ser Lys Val Ala Phe Leu Thr Val Thr Leu His Gln 675 680 685 Gly Gly Ala Thr Arg Met Tyr Ala Leu Ile Ser Asp Ala Gln Pro Leu 690 695 700 Leu Leu Ser Thr Phe Ser Gly Asp Arg Arg Phe Ser Arg Phe Gly Gly 705 710 715 720 Val Leu His Leu Ser Asp Leu Asp Asp Asp Gly Leu Asp Glu Ile Ile 725 730 735 Met Ala Ala Pro Leu Arg Ile Ala Asp Val Thr Ser Gly Leu Ile Gly 740 745 750 Gly Glu Asp Gly Arg Val Tyr Val Tyr Asn Gly Lys Glu Thr Thr Leu 755 760 765 Gly Asp Met Thr Gly Lys Cys Lys Ser Trp Ile Thr Pro Cys Pro Glu 770 775 780 Glu Lys Ala Gln Tyr Val Leu Ile Ser Pro Glu Ala Ser Ser Arg Phe 785 790 795 800 Gly Ser Ser Leu Ile Thr Val Arg Ser Lys Ala Lys Asn Gln Val Val 805 810 815 Ile Ala Ala Gly Arg Ser Ser Leu Gly Ala Arg Leu Ser Gly Ala Leu 820 825 830 His Val Tyr Ser Leu Gly Ser Asp 835 840 <210> 44 <211> 493 <212> PRT <213> Homo sapiens <400> 44 Met Ala Leu Phe Gly Ala Leu Phe Leu Ala Leu Leu Ala Gly Ala His 1 5 10 15 Ala Glu Phe Pro Gly Cys Lys Ile Arg Val Thr Ser Lys Ala Leu Glu 20 25 30 Leu Val Lys Gln Glu Gly Leu Arg Phe Leu Glu Gln Glu Leu Glu Thr 35 40 45 Ile Thr Ile Pro Asp Leu Arg Gly Lys Glu Gly His Phe Tyr Tyr Asn 50 55 60 Ile Ser Glu Val Lys Val Thr Glu Leu Gln Leu Thr Ser Ser Glu Leu 65 70 75 80 Asp Phe Gln Pro Gln Gln Glu Leu Met Leu Gln Ile Thr Asn Ala Ser 85 90 95 Leu Gly Leu Arg Phe Arg Arg Gln Leu Leu Tyr Trp Phe Phe Tyr Asp 100 105 110 Gly Gly Tyr Ile Asn Ala Ser Ala Glu Gly Val Ser Ile Arg Thr Gly 115 120 125 Leu Glu Leu Ser Arg Asp Pro Ala Gly Arg Met Lys Val Ser Asn Val 130 135 140 Ser Cys Gln Ala Ser Val Ser Arg Met His Ala Ala Phe Gly Gly Thr 145 150 155 160 Phe Lys Lys Val Tyr Asp Phe Leu Ser Thr Phe Ile Thr Ser Gly Met 165 170 175 Arg Phe Leu Leu Asn Gln Gln Ile Cys Pro Val Leu Tyr His Ala Gly 180 185 190 Thr Val Leu Leu Asn Ser Leu Leu Asp Thr Val Pro Val Arg Ser Ser 195 200 205 Val Asp Glu Leu Val Gly Ile Asp Tyr Ser Leu Met Lys Asp Pro Val 210 215 220 Ala Ser Thr Ser Asn Leu Asp Met Asp Phe Arg Gly Ala Phe Phe Pro 225 230 235 240 Leu Thr Glu Arg Asn Trp Ser Leu Pro Asn Arg Ala Val Glu Pro Gln 245 250 255 Leu Gln Glu Glu Glu Arg Met Val Tyr Val Ala Phe Ser Glu Phe Phe 260 265 270 Phe Asp Ser Ala Met Glu Ser Tyr Phe Arg Ala Gly Ala Leu Gln Leu 275 280 285 Leu Leu Val Gly Asp Lys Val Pro His Asp Leu Asp Met Leu Leu Arg 290 295 300 Ala Thr Tyr Phe Gly Ser Ile Val Leu Leu Ser Pro Ala Val Ile Asp 305 310 315 320 Ser Pro Leu Lys Leu Glu Leu Arg Val Leu Ala Pro Pro Arg Cys Thr 325 330 335 Ile Lys Pro Ser Gly Thr Thr Ile Ser Val Thr Ala Ser Val Thr Ile 340 345 350 Ala Leu Val Pro Pro Asp Gln Pro Glu Val Gln Leu Ser Ser Met Thr 355 360 365 Met Asp Ala Arg Leu Ser Ala Lys Met Ala Leu Arg Gly Lys Ala Leu 370 375 380 Arg Thr Gln Leu Asp Leu Arg Arg Phe Arg Ile Tyr Ser Asn His Ser 385 390 395 400 Ala Leu Glu Ser Leu Ala Leu Ile Pro Leu Gln Ala Pro Leu Lys Thr 405 410 415 Met Leu Gln Ile Gly Val Met Pro Met Leu Asn Glu Arg Thr Trp Arg 420 425 430 Gly Val Gln Ile Pro Leu Pro Glu Gly Ile Asn Phe Val His Glu Val 435 440 445 Val Thr Asn His Ala Gly Phe Leu Thr Ile Gly Ala Asp Leu His Phe 450 455 460 Ala Lys Gly Leu Arg Glu Val Ile Glu Lys Asn Arg Pro Ala Asp Val 465 470 475 480 Arg Ala Ser Thr Ala Pro Thr Pro Ser Thr Ala Ala Val 485 490 <210> 45 <211> 480 <212> PRT <213> Homo sapiens <400> 45 Met Ala Arg Phe Pro Lys Ala Asp Leu Ala Ala Ala Gly Val Met Leu 1 5 10 15 Leu Cys His Phe Phe Thr Asp Gln Phe Gln Phe Ala Asp Gly Lys Pro 20 25 30 Gly Asp Gln Ile Leu Asp Trp Gln Tyr Gly Val Thr Gln Ala Phe Pro 35 40 45 His Thr Glu Glu Glu Val Glu Val Asp Ser His Ala Tyr Ser His Arg 50 55 60 Trp Lys Arg Asn Leu Asp Phe Leu Lys Ala Val Asp Thr Asn Arg Ala 65 70 75 80 Ser Val Gly Gln Asp Ser Pro Glu Pro Arg Ser Phe Thr Asp Leu Leu 85 90 95 Leu Asp Asp Gly Gln Asp Asn Asn Thr Gln Ile Glu Glu Asp Thr Asp 100 105 110 His Asn Tyr Tyr Ile Ser Arg Ile Tyr Gly Pro Ser Asp Ser Ala Ser 115 120 125 Arg Asp Leu Trp Val Asn Ile Asp Gln Met Glu Lys Asp Lys Val Lys 130 135 140 Ile His Gly Ile Leu Ser Asn Thr His Arg Gln Ala Ala Arg Val Asn 145 150 155 160 Leu Ser Phe Asp Phe Pro Phe Tyr Gly His Phe Leu Arg Glu Ile Thr 165 170 175 Val Ala Thr Gly Gly Phe Ile Tyr Thr Gly Glu Val Val His Arg Met 180 185 190 Leu Thr Ala Thr Gln Tyr Ile Ala Pro Leu Met Ala Asn Phe Asp Pro 195 200 205 Ser Val Ser Arg Asn Ser Thr Val Arg Tyr Phe Asp Asn Gly Thr Ala 210 215 220 Leu Val Val Gln Trp Asp His Val His Leu Gln Asp Asn Tyr Asn Leu 225 230 235 240 Gly Ser Phe Thr Phe Gln Ala Thr Leu Leu Met Asp Gly Arg Ile Ile 245 250 255 Phe Gly Tyr Lys Glu Ile Pro Val Leu Val Thr Gln Ile Ser Ser Thr 260 265 270 Asn His Pro Val Lys Val Gly Leu Ser Asp Ala Phe Val Val Val His 275 280 285 Arg Ile Gln Gln Ile Pro Asn Val Arg Arg Arg Thr Ile Tyr Glu Tyr 290 295 300 His Arg Val Glu Leu Gln Met Ser Lys Ile Thr Asn Ile Ser Ala Val 305 310 315 320 Glu Met Thr Pro Leu Pro Thr Cys Leu Gln Phe Asn Arg Cys Gly Pro 325 330 335 Cys Val Ser Ser Gln Ile Gly Phe Asn Cys Ser Trp Cys Ser Lys Leu 340 345 350 Gln Arg Cys Ser Ser Gly Phe Asp Arg His Arg Gln Asp Trp Val Asp 355 360 365 Ser Gly Cys Pro Glu Glu Ser Lys Glu Lys Met Cys Glu Asn Thr Glu 370 375 380 Pro Val Glu Thr Ser Ser Arg Thr Thr Thr Thr Val Gly Ala Thr Thr 385 390 395 400 Thr Gln Phe Arg Val Leu Thr Thr Thr Arg Arg Ala Val Thr Ser Gln 405 410 415 Phe Pro Thr Ser Leu Pro Thr Glu Asp Asp Thr Lys Ile Ala Leu His 420 425 430 Leu Lys Asp Asn Gly Ala Ser Thr Asp Asp Ser Ala Ala Glu Lys Lys 435 440 445 Gly Gly Thr Leu His Ala Gly Leu Ile Ile Gly Ile Leu Ile Leu Val 450 455 460 Leu Ile Val Ala Thr Ala Ile Leu Val Thr Val Tyr Met Tyr His His 465 470 475 480 <210> 46 <211> 2677 <212> PRT <213> Homo sapiens <400> 46 Met Ser Thr Cys Cys Trp Cys Thr Pro Gly Gly Ala Ser Thr Ile Asp 1 5 10 15 Phe Leu Lys Arg Tyr Ala Ser Asn Thr Pro Ser Gly Glu Phe Gln Thr 20 25 30 Ala Asp Glu Asp Leu Cys Tyr Cys Leu Glu Cys Val Ala Glu Tyr His 35 40 45 Lys Ala Arg Asp Glu Leu Pro Phe Leu His Glu Val Leu Trp Glu Leu 50 55 60 Glu Thr Leu Arg Leu Ile Asn His Phe Glu Lys Ser Met Lys Ala Glu 65 70 75 80 Ile Gly Asp Asp Asp Glu Leu Tyr Ile Val Asp Asn Asn Gly Glu Met 85 90 95 Pro Leu Phe Asp Ile Thr Gly Gln Asp Phe Glu Asn Lys Leu Arg Val 100 105 110 Pro Leu Leu Glu Ile Leu Lys Tyr Pro Tyr Leu Leu Leu His Glu Arg 115 120 125 Val Asn Glu Leu Cys Val Glu Ala Leu Cys Arg Met Glu Gln Ala Asn 130 135 140 Cys Ser Phe Gln Val Phe Asp Lys His Pro Gly Ile Tyr Leu Phe Leu 145 150 155 160 Val His Pro Asn Glu Met Val Arg Arg Trp Ala Ile Leu Thr Ala Arg 165 170 175 Asn Leu Gly Lys Val Asp Arg Asp Asp Tyr Tyr Asp Leu Gln Glu Val 180 185 190 Leu Leu Cys Leu Phe Lys Val Ile Glu Leu Gly Leu Leu Glu Ser Pro 195 200 205 Asp Ile Tyr Thr Ser Ser Val Leu Glu Lys Gly Lys Leu Ile Leu Leu 210 215 220 Pro Ser His Met Tyr Asp Thr Thr Asn Tyr Lys Ser Tyr Trp Leu Gly 225 230 235 240 Ile Cys Met Leu Leu Thr Ile Leu Glu Glu Gln Ala Met Asp Ser Leu 245 250 255 Leu Leu Gly Ser Asp Lys Gln Asn Asp Phe Met Gln Ser Ile Leu His 260 265 270 Thr Met Glu Arg Glu Ala Asp Asp Asp Ser Val Asp Pro Phe Trp Pro 275 280 285 Ala Leu His Cys Phe Met Val Ile Leu Asp Arg Leu Gly Ser Lys Val 290 295 300 Trp Gly Gln Leu Met Asp Pro Ile Val Ala Phe Gln Thr Ile Ile Asn 305 310 315 320 Asn Ala Ser Tyr Asn Arg Glu Ile Arg His Ile Arg Asn Ser Ser Val 325 330 335 Arg Thr Lys Leu Glu Pro Glu Ser Tyr Leu Asp Asp Met Val Thr Cys 340 345 350 Ser Gln Ile Val Tyr Asn Tyr Asn Pro Glu Lys Thr Lys Lys Asp Ser 355 360 365 Gly Trp Arg Thr Ala Ile Cys Pro Asp Tyr Cys Pro Asn Met Tyr Glu 370 375 380 Glu Met Glu Thr Leu Ala Ser Val Leu Gln Ser Asp Ile Gly Gln Asp 385 390 395 400 Met Arg Val His Asn Ser Thr Phe Leu Trp Phe Ile Pro Phe Val Gln 405 410 415 Ser Leu Met Asp Leu Lys Asp Leu Gly Val Ala Tyr Ile Ala Gln Val 420 425 430 Val Asn His Leu Tyr Ser Glu Val Lys Glu Val Leu Asn Gln Thr Asp 435 440 445 Ala Val Cys Asp Lys Val Thr Glu Phe Phe Leu Leu Ile Leu Val Ser 450 455 460 Val Ile Glu Leu His Arg Asn Lys Lys Cys Leu His Leu Leu Trp Val 465 470 475 480 Ser Ser Gln Gln Trp Val Glu Ala Val Val Lys Cys Ala Lys Leu Pro 485 490 495 Thr Thr Ala Phe Thr Arg Ser Ser Glu Lys Ser Ser Gly Asn Cys Ser 500 505 510 Lys Gly Thr Ala Met Ile Ser Ser Leu Ser Leu His Ser Met Pro Ser 515 520 525 Asn Ser Val Gln Leu Ala Tyr Val Gln Leu Ile Arg Ser Leu Leu Lys 530 535 540 Glu Gly Tyr Gln Leu Gly Gln Gln Ser Leu Cys Lys Arg Phe Trp Asp 545 550 555 560 Lys Leu Asn Leu Phe Leu Arg Gly Asn Leu Ser Leu Gly Trp Gln Leu 565 570 575 Thr Ser Gln Glu Thr His Glu Leu Gln Ser Cys Leu Lys Gln Ile Ile 580 585 590 Arg Asn Ile Lys Phe Lys Ala Pro Pro Cys Asn Thr Phe Val Asp Leu 595 600 605 Thr Ser Ala Cys Lys Ile Ser Pro Ala Ser Tyr Asn Lys Glu Glu Ser 610 615 620 Glu Gln Met Gly Lys Thr Ser Arg Lys Asp Met His Cys Leu Glu Ala 625 630 635 640 Ser Ser Pro Thr Phe Ser Lys Glu Pro Met Lys Val Gln Asp Ser Val 645 650 655 Ser Ile Lys Ala Asp Asn Thr Ile Glu Gly Asp Asn Asn Glu Gln Asn 660 665 670 Tyr Ile Lys Asp Val Lys Leu Glu Asp His Leu Leu Ala Gly Ser Cys 675 680 685 Leu Lys Gln Ser Ser Lys Asn Ile Phe Thr Glu Arg Ala Glu Asp Gln 690 695 700 Ile Lys Ile Ser Thr Arg Lys Gln Lys Ser Val Lys Glu Ile Ser Ser 705 710 715 720 Tyr Thr Pro Lys Asp Cys Thr Ser Arg Asn Gly Pro Glu Arg Gly Cys 725 730 735 Asp Arg Gly Ile Ile Val Ser Thr Arg Leu Leu Thr Asp Ser Ser Thr 740 745 750 Asp Ala Leu Glu Lys Val Ser Thr Ser Asn Glu Asp Phe Ser Leu Lys 755 760 765 Asp Asp Ala Leu Ala Lys Thr Ser Lys Arg Lys Thr Lys Val Gln Lys 770 775 780 Asp Glu Ile Cys Ala Lys Leu Ser His Val Ile Lys Lys Gln His Arg 785 790 795 800 Lys Ser Thr Leu Val Asp Asn Thr Ile Asn Leu Asp Glu Asn Leu Thr 805 810 815 Val Ser Asn Ile Glu Ser Phe Tyr Ser Arg Lys Asp Thr Gly Val Gln 820 825 830 Lys Gly Asp Gly Phe Ile His Asn Leu Ser Leu Asp Pro Ser Gly Val 835 840 845 Leu Asp Asp Lys Asn Gly Glu Gln Lys Ser Gln Asn Asn Val Leu Pro 850 855 860 Lys Glu Lys Gln Leu Lys Asn Glu Glu Leu Val Ile Phe Ser Phe His 865 870 875 880 Glu Asn Asn Cys Lys Ile Gln Glu Phe His Val Asp Gly Lys Glu Leu 885 890 895 Ile Pro Phe Thr Glu Met Thr Asn Ala Ser Glu Lys Lys Ser Ser Pro 900 905 910 Phe Lys Asp Leu Met Thr Val Pro Glu Ser Arg Asp Glu Glu Met Ser 915 920 925 Asn Ser Thr Ser Val Ile Tyr Ser Asn Leu Thr Arg Glu Gln Ala Pro 930 935 940 Asp Ile Ser Pro Lys Ser Asp Thr Leu Thr Asp Ser Gln Ile Asp Arg 945 950 955 960 Asp Leu His Lys Leu Ser Leu Leu Ala Gln Ala Ser Val Ile Thr Phe 965 970 975 Pro Ser Asp Ser Pro Gln Asn Ser Ser Gln Leu Gln Arg Lys Val Lys 980 985 990 Glu Asp Lys Arg Cys Phe Thr Ala Asn Gln Asn Asn Val Gly Asp Thr 995 1000 1005 Ser Arg Gly Gln Val Ile Ile Ile Ser Asp Ser Asp Asp Asp Asp Asp 1010 1015 1020 Glu Arg Ile Leu Ser Leu Glu Lys Leu Thr Lys Gln Asp Lys Ile Cys 1025 1030 1035 1040 Leu Glu Arg Glu His Pro Glu Gln His Val Ser Thr Val Asn Ser Lys 1045 1050 1055 Glu Glu Lys Asn Pro Val Lys Glu Glu Lys Thr Glu Thr Leu Phe Gln 1060 1065 1070 Phe Glu Glu Ser Asp Ser Gln Cys Phe Glu Phe Glu Ser Ser Ser Glu 1075 1080 1085 Val Phe Ser Val Trp Gln Asp His Pro Asp Asp Asn Asn Ser Val Gln 1090 1095 1100 Asp Gly Glu Lys Lys Cys Leu Ala Pro Ile Ala Asn Thr Thr Asn Gly 1105 1110 1115 1120 Gln Gly Cys Thr Asp Tyr Val Ser Glu Val Val Lys Lys Gly Ala Glu 1125 1130 1135 Gly Ile Glu Glu His Thr Arg Pro Arg Ser Ile Ser Val Glu Glu Phe 1140 1145 1150 Cys Glu Ile Glu Val Lys Lys Pro Lys Arg Lys Arg Ser Glu Lys Pro 1155 1160 1165 Met Ala Glu Asp Pro Val Arg Pro Ser Ser Ser Val Arg Asn Glu Gly 1170 1175 1180 Gln Ser Asp Thr Asn Lys Arg Glu Leu Val Gly Asn Asp Phe Lys Ser 1185 1190 1195 1200 Ile Asp Arg Arg Thr Ser Thr Pro Asn Ser Arg Ile Gln Arg Ala Thr 1205 1210 1215 Thr Val Ser Gln Lys Lys Ser Ser Lys Leu Cys Thr Cys Thr Glu Pro 1220 1225 1230 Ile Arg Lys Val Pro Val Ser Lys Thr Pro Lys Lys Thr His Ser Asp 1235 1240 1245 Ala Lys Lys Arg Gln Asn Arg Ser Ser Asn Tyr Leu Ser Cys Arg Thr 1250 1255 1260 Thr Pro Ala Ile Val Pro Pro Lys Lys Phe Arg Gln Cys Pro Glu Pro 1265 1270 1275 1280 Thr Ser Thr Ala Glu Lys Leu Gly Leu Lys Lys Gly Pro Arg Lys Ala 1285 1290 1295 Tyr Glu Leu Ser Gln Arg Ser Leu Asp Tyr Val Ala Gln Leu Arg Asp 1300 1305 1310 His Gly Lys Thr Val Gly Val Val Asp Thr Arg Lys Lys Thr Lys Leu 1315 1320 1325 Ile Ser Pro Gln Asn Leu Ser Val Arg Asn Asn Lys Lys Leu Leu Thr 1330 1335 1340 Ser Gln Glu Leu Gln Met Gln Arg Gln Ile Arg Pro Lys Ser Gln Lys 1345 1350 1355 1360 Asn Arg Arg Arg Leu Ser Asp Cys Glu Ser Thr Asp Val Lys Arg Ala 1365 1370 1375 Gly Ser His Thr Ala Gln Asn Ser Asp Val Phe Val Pro Glu Ser Asp 1380 1385 1390 Arg Ser Asp Tyr Asn Cys Thr Gly Gly Thr Glu Val Leu Ala Asn Ser 1395 1400 1405 Asn Arg Lys Gln Leu Ile Lys Cys Met Pro Ser Glu Pro Glu Thr Ile 1410 1415 1420 Lys Ala Lys His Gly Ser Pro Ala Thr Asp Asp Ala Cys Pro Leu Asn 1425 1430 1435 1440 Gln Cys Asp Ser Val Val Leu Asn Gly Thr Val Pro Thr Asn Glu Val 1445 1450 1455 Ile Val Ser Thr Ser Glu Asp Pro Leu Gly Gly Gly Asp Pro Thr Ala 1460 1465 1470 Arg His Ile Glu Met Ala Ala Leu Lys Glu Gly Glu Pro Asp Ser Ser 1475 1480 1485 Ser Asp Ala Glu Glu Asp Asn Leu Phe Leu Thr Gln Asn Asp Pro Glu 1490 1495 1500 Asp Met Asp Leu Cys Ser Gln Met Glu Asn Asp Asn Tyr Lys Leu Ile 1505 1510 1515 1520 Glu Leu Ile His Gly Lys Asp Thr Val Glu Val Glu Glu Asp Ser Val 1525 1530 1535 Ser Arg Pro Gln Leu Glu Ser Leu Ser Gly Thr Lys Cys Lys Tyr Lys 1540 1545 1550 Asp Cys Leu Glu Thr Thr Lys Asn Gln Gly Glu Tyr Cys Pro Lys His 1555 1560 1565 Ser Glu Val Lys Ala Ala Asp Glu Asp Val Phe Arg Lys Pro Gly Leu 1570 1575 1580 Pro Pro Pro Ala Ser Lys Pro Leu Arg Pro Thr Thr Lys Ile Phe Ser 1585 1590 1595 1600 Ser Lys Ser Thr Ser Arg Ile Ala Gly Leu Ser Lys Ser Leu Glu Thr 1605 1610 1615 Ser Ser Ala Leu Ser Pro Ser Leu Lys Asn Lys Ser Lys Gly Ile Gln 1620 1625 1630 Ser Ile Leu Lys Val Pro Gln Pro Val Pro Leu Ile Ala Gln Lys Pro 1635 1640 1645 Val Gly Glu Met Lys Asn Ser Cys Asn Val Leu His Pro Gln Ser Pro 1650 1655 1660 Asn Asn Ser Asn Arg Gln Gly Cys Lys Val Pro Phe Gly Glu Ser Lys 1665 1670 1675 1680 Tyr Phe Pro Ser Ser Ser Pro Val Asn Ile Leu Leu Ser Ser Gln Ser 1685 1690 1695 Val Ser Asp Thr Phe Val Lys Glu Val Leu Lys Trp Lys Tyr Glu Met 1700 1705 1710 Phe Leu Asn Phe Gly Gln Cys Gly Pro Pro Ala Ser Leu Cys Gln Ser 1715 1720 1725 Ile Ser Arg Pro Val Pro Val Arg Phe His Asn Tyr Gly Asp Tyr Phe 1730 1735 1740 Asn Val Phe Phe Pro Leu Met Val Leu Asn Thr Phe Glu Thr Val Ala 1745 1750 1755 1760 Gln Glu Trp Leu Asn Ser Pro Asn Arg Glu Asn Phe Tyr Gln Leu Gln 1765 1770 1775 Val Arg Lys Phe Pro Ala Asp Tyr Ile Lys Tyr Trp Glu Phe Ala Val 1780 1785 1790 Tyr Leu Glu Glu Cys Glu Leu Ala Lys Gln Leu Tyr Pro Lys Glu Asn 1795 1800 1805 Asp Leu Val Phe Leu Ala Pro Glu Arg Ile Asn Glu Glu Lys Lys Asp 1810 1815 1820 Thr Glu Arg Asn Asp Ile Gln Asp Leu His Glu Tyr His Ser Gly Tyr 1825 1830 1835 1840 Val His Lys Phe Arg Arg Thr Ser Val Met Arg Asn Gly Lys Thr Glu 1845 1850 1855 Cys Tyr Leu Ser Ile Gln Thr Gln Glu Asn Phe Pro Ala Asn Leu Asn 1860 1865 1870 Glu Leu Val Asn Cys Ile Val Ile Ser Ser Leu Val Thr Thr Gln Arg 1875 1880 1885 Lys Leu Lys Ala Met Ser Leu Leu Gly Ser Arg Asn Gln Leu Ala Arg 1890 1895 1900 Ala Val Leu Asn Pro Asn Pro Met Asp Phe Cys Thr Lys Asp Leu Leu 1905 1910 1915 1920 Thr Thr Thr Ser Glu Arg Ile Ile Ala Tyr Leu Arg Asp Phe Asn Glu 1925 1930 1935 Asp Gln Lys Lys Ala Ile Glu Thr Ala Tyr Ala Met Val Lys His Ser 1940 1945 1950 Pro Ser Val Ala Lys Ile Cys Leu Ile His Gly Pro Pro Gly Thr Gly 1955 1960 1965 Lys Ser Lys Thr Ile Val Gly Leu Leu Tyr Arg Leu Leu Thr Glu Asn 1970 1975 1980 Gln Arg Lys Gly His Ser Asp Glu Asn Ser Asn Ala Lys Ile Lys Gln 1985 1990 1995 2000 Asn Arg Val Leu Val Cys Ala Pro Ser Asn Ala Ala Val Asp Glu Leu 2005 2010 2015 Met Lys Lys Ile Ile Leu Glu Phe Lys Glu Lys Cys Lys Asp Lys Lys 2020 2025 2030 Asn Pro Leu Gly Asn Cys Gly Asp Ile Asn Leu Val Arg Leu Gly Pro 2035 2040 2045 Glu Lys Ser Ile Asn Ser Glu Val Leu Lys Phe Ser Leu Asp Ser Gln 2050 2055 2060 Val Asn His Arg Met Lys Lys Glu Leu Pro Ser His Val Gln Ala Met 2065 2070 2075 2080 His Lys Arg Lys Glu Phe Leu Asp Tyr Gln Leu Asp Glu Leu Ser Arg 2085 2090 2095 Gln Arg Ala Leu Cys Arg Gly Gly Arg Glu Ile Gln Arg Gln Glu Leu 2100 2105 2110 Asp Glu Asn Ile Ser Lys Val Ser Lys Glu Arg Gln Glu Leu Ala Ser 2115 2120 2125 Lys Ile Lys Glu Val Gln Gly Arg Pro Gln Lys Thr Gln Ser Ile Ile 2130 2135 2140 Ile Leu Glu Ser His Ile Ile Cys Cys Thr Leu Ser Thr Ser Gly Gly 2145 2150 2155 2160 Leu Leu Leu Glu Ser Ala Phe Arg Gly Gln Gly Gly Val Pro Phe Ser 2165 2170 2175 Cys Val Ile Val Asp Glu Ala Gly Gln Ser Cys Glu Ile Glu Thr Leu 2180 2185 2190 Thr Pro Leu Ile His Arg Cys Asn Lys Leu Ile Leu Val Gly Asp Pro 2195 2200 2205 Lys Gln Leu Pro Pro Thr Val Ile Ser Met Lys Ala Gln Glu Tyr Gly 2210 2215 2220 Tyr Asp Gln Ser Met Met Ala Arg Phe Cys Arg Leu Leu Glu Glu Asn 2225 2230 2235 2240 Val Glu His Asn Met Ile Ser Arg Leu Pro Ile Leu Gln Leu Thr Val 2245 2250 2255 Gln Tyr Arg Met His Pro Asp Ile Cys Leu Phe Pro Ser Asn Tyr Val 2260 2265 2270 Tyr Asn Arg Asn Leu Lys Thr Asn Arg Gln Thr Glu Ala Ile Arg Cys 2275 2280 2285 Ser Ser Asp Trp Pro Phe Gln Pro Tyr Leu Val Phe Asp Val Gly Asp 2290 2295 2300 Gly Ser Glu Arg Arg Asp Asn Asp Ser Tyr Ile Asn Val Gln Glu Ile 2305 2310 2315 2320 Lys Leu Val Met Glu Ile Ile Lys Leu Ile Lys Asp Lys Arg Lys Asp 2325 2330 2335 Val Ser Phe Arg Asn Ile Gly Ile Ile Thr His Tyr Lys Ala Gln Lys 2340 2345 2350 Thr Met Ile Gln Lys Asp Leu Asp Lys Glu Phe Asp Arg Lys Gly Pro 2355 2360 2365 Ala Glu Val Asp Thr Val Asp Ala Phe Gln Gly Arg Gln Lys Asp Cys 2370 2375 2380 Val Ile Val Thr Cys Val Arg Ala Asn Ser Ile Gln Gly Ser Ile Gly 2385 2390 2395 2400 Phe Leu Ala Ser Leu Gln Arg Leu Asn Val Thr Ile Thr Arg Ala Lys 2405 2410 2415 Tyr Ser Leu Phe Ile Leu Gly His Leu Arg Thr Leu Met Glu Asn Gln 2420 2425 2430 His Trp Asn Gln Leu Ile Gln Asp Ala Gln Lys Arg Gly Ala Ile Ile 2435 2440 2445 Lys Thr Cys Asp Lys Asn Tyr Arg His Asp Ala Val Lys Ile Leu Lys 2450 2455 2460 Leu Lys Pro Val Leu Gln Arg Ser Leu Thr His Pro Pro Thr Ile Ala 2465 2470 2475 2480 Pro Glu Gly Ser Arg Pro Gln Gly Gly Leu Pro Ser Ser Lys Leu Asp 2485 2490 2495 Ser Gly Phe Ala Lys Thr Ser Val Ala Ala Ser Leu Tyr His Thr Pro 2500 2505 2510 Ser Asp Ser Lys Glu Ile Thr Leu Thr Val Thr Ser Lys Asp Pro Glu 2515 2520 2525 Arg Pro Pro Val His Asp Gln Leu Gln Asp Pro Arg Leu Leu Lys Arg 2530 2535 2540 Met Gly Ile Glu Val Lys Gly Gly Ile Phe Leu Trp Asp Pro Gln Pro 2545 2550 2555 2560 Ser Ser Pro Gln His Pro Gly Ala Thr Pro Pro Thr Gly Glu Pro Gly 2565 2570 2575 Phe Pro Val Val His Gln Asp Leu Ser His Ile Gln Gln Pro Ala Ala 2580 2585 2590 Val Val Ala Ala Leu Ser Ser His Lys Pro Pro Val Arg Gly Glu Pro 2595 2600 2605 Pro Ala Ala Ser Pro Glu Ala Ser Thr Cys Gln Ser Lys Cys Asp Asp 2610 2615 2620 Pro Glu Glu Glu Leu Cys His Arg Arg Glu Ala Arg Ala Phe Ser Glu 2625 2630 2635 2640 Gly Glu Gln Glu Lys Cys Gly Ser Glu Thr His His Thr Arg Arg Asn 2645 2650 2655 Ser Arg Trp Asp Lys Arg Thr Leu Glu Gln Glu Asp Ser Ser Ser Lys 2660 2665 2670 Lys Arg Lys Leu Leu 2675 <210> 47 <211> 1404 <212> PRT <213> Homo sapiens <400> 47 Met Ala Trp Lys Thr Leu Pro Ile Tyr Leu Leu Leu Leu Leu Ser Val 1 5 10 15 Phe Val Ile Gln Gln Val Ser Ser Gln Asp Leu Ser Ser Cys Ala Gly 20 25 30 Arg Cys Gly Glu Gly Tyr Ser Arg Asp Ala Thr Cys Asn Cys Asp Tyr 35 40 45 Asn Cys Gln His Tyr Met Glu Cys Cys Pro Asp Phe Lys Arg Val Cys 50 55 60 Thr Ala Glu Leu Ser Cys Lys Gly Arg Cys Phe Glu Ser Phe Glu Arg 65 70 75 80 Gly Arg Glu Cys Asp Cys Asp Ala Gln Cys Lys Lys Tyr Asp Lys Cys 85 90 95 Cys Pro Asp Tyr Glu Ser Phe Cys Ala Glu Val His Asn Pro Thr Ser 100 105 110 Pro Pro Ser Ser Lys Lys Ala Pro Pro Pro Ser Gly Ala Ser Gln Thr 115 120 125 Ile Lys Ser Thr Thr Lys Arg Ser Pro Lys Pro Pro Asn Lys Lys Lys 130 135 140 Thr Lys Lys Val Ile Glu Ser Glu Glu Ile Thr Glu Glu His Ser Val 145 150 155 160 Ser Glu Asn Gln Glu Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser 165 170 175 Ser Thr Ile Arg Lys Ile Lys Ser Ser Lys Asn Ser Ala Ala Asn Arg 180 185 190 Glu Leu Gln Lys Lys Leu Lys Val Lys Asp Asn Lys Lys Asn Arg Thr 195 200 205 Lys Lys Lys Pro Thr Pro Lys Pro Pro Val Val Asp Glu Ala Gly Ser 210 215 220 Gly Leu Asp Asn Gly Asp Phe Lys Val Thr Thr Pro Asp Thr Ser Thr 225 230 235 240 Thr Gln His Asn Lys Val Ser Thr Ser Pro Lys Ile Thr Thr Ala Lys 245 250 255 Pro Ile Asn Pro Arg Pro Ser Leu Pro Pro Asn Ser Asp Thr Ser Lys 260 265 270 Glu Thr Ser Leu Thr Val Asn Lys Glu Thr Thr Val Glu Thr Lys Glu 275 280 285 Thr Thr Thr Thr Asn Lys Gln Thr Ser Thr Asp Gly Lys Glu Lys Thr 290 295 300 Thr Ser Ala Lys Glu Thr Gln Ser Ile Glu Lys Thr Ser Ala Lys Asp 305 310 315 320 Leu Ala Pro Thr Ser Lys Val Leu Ala Lys Pro Thr Pro Lys Ala Glu 325 330 335 Thr Thr Thr Lys Gly Pro Ala Leu Thr Thr Pro Lys Glu Pro Thr Pro 340 345 350 Thr Thr Pro Lys Glu Pro Ala Ser Thr Thr Pro Lys Glu Pro Thr Pro 355 360 365 Thr Thr Ile Lys Ser Ala Pro Thr Thr Pro Lys Glu Pro Ala Pro Thr 370 375 380 Thr Thr Lys Ser Ala Pro Thr Thr Pro Lys Glu Pro Ala Pro Thr Thr 385 390 395 400 Thr Lys Glu Pro Ala Pro Thr Thr Pro Lys Glu Pro Ala Pro Thr Thr 405 410 415 Thr Lys Glu Pro Ala Pro Thr Thr Thr Lys Ser Ala Pro Thr Thr Pro 420 425 430 Lys Glu Pro Ala Pro Thr Thr Pro Lys Lys Pro Ala Pro Thr Thr Pro 435 440 445 Lys Glu Pro Ala Pro Thr Thr Pro Lys Glu Pro Thr Pro Thr Thr Pro 450 455 460 Lys Glu Pro Ala Pro Thr Thr Lys Glu Pro Ala Pro Thr Thr Pro Lys 465 470 475 480 Glu Pro Ala Pro Thr Ala Pro Lys Lys Pro Ala Pro Thr Thr Pro Lys 485 490 495 Glu Pro Ala Pro Thr Thr Pro Lys Glu Pro Ala Pro Thr Thr Thr Lys 500 505 510 Glu Pro Ser Pro Thr Thr Pro Lys Glu Pro Ala Pro Thr Thr Thr Lys 515 520 525 Ser Ala Pro Thr Thr Thr Lys Glu Pro Ala Pro Thr Thr Thr Lys Ser 530 535 540 Ala Pro Thr Thr Pro Lys Glu Pro Ser Pro Thr Thr Thr Lys Glu Pro 545 550 555 560 Ala Pro Thr Thr Pro Lys Glu Pro Ala Pro Thr Thr Pro Lys Lys Pro 565 570 575 Ala Pro Thr Thr Pro Lys Glu Pro Ala Pro Thr Thr Pro Lys Glu Pro 580 585 590 Ala Pro Thr Thr Thr Lys Lys Pro Ala Pro Thr Thr Pro Lys Glu Pro 595 600 605 Ala Pro Thr Thr Pro Lys Glu Thr Ala Pro Thr Thr Pro Lys Lys Leu 610 615 620 Thr Pro Thr Thr Pro Glu Lys Leu Ala Pro Thr Thr Pro Glu Lys Pro 625 630 635 640 Ala Pro Thr Thr Pro Glu Glu Leu Ala Pro Thr Thr Pro Glu Glu Pro 645 650 655 Thr Pro Thr Thr Pro Glu Glu Pro Ala Pro Thr Thr Pro Lys Ala Ala 660 665 670 Ala Pro Asn Thr Pro Lys Glu Pro Ala Pro Thr Thr Pro Lys Glu Pro 675 680 685 Ala Pro Thr Thr Pro Lys Glu Pro Ala Pro Thr Thr Pro Lys Glu Thr 690 695 700 Ala Pro Thr Thr Pro Lys Gly Thr Ala Pro Thr Thr Leu Lys Glu Pro 705 710 715 720 Ala Pro Thr Thr Pro Lys Lys Pro Ala Pro Lys Glu Leu Ala Pro Thr 725 730 735 Thr Thr Lys Glu Pro Thr Ser Thr Thr Cys Asp Lys Pro Ala Pro Thr 740 745 750 Thr Pro Lys Gly Thr Ala Pro Thr Thr Pro Lys Glu Pro Ala Pro Thr 755 760 765 Thr Pro Lys Glu Pro Ala Pro Thr Thr Pro Lys Gly Thr Ala Pro Thr 770 775 780 Thr Leu Lys Glu Pro Ala Pro Thr Thr Pro Lys Lys Pro Ala Pro Lys 785 790 795 800 Glu Leu Ala Pro Thr Thr Thr Lys Gly Pro Thr Ser Thr Thr Ser Asp 805 810 815 Lys Pro Ala Pro Thr Thr Pro Lys Glu Thr Ala Pro Thr Thr Pro Lys 820 825 830 Glu Pro Ala Pro Thr Thr Pro Lys Lys Pro Ala Pro Thr Thr Pro Glu 835 840 845 Thr Pro Pro Pro Thr Thr Ser Glu Val Ser Thr Pro Thr Thr Thr Lys 850 855 860 Glu Pro Thr Thr Ile His Lys Ser Pro Asp Glu Ser Thr Pro Glu Leu 865 870 875 880 Ser Ala Glu Pro Thr Pro Lys Ala Leu Glu Asn Ser Pro Lys Glu Pro 885 890 895 Gly Val Pro Thr Thr Lys Thr Pro Ala Ala Thr Lys Pro Glu Met Thr 900 905 910 Thr Thr Ala Lys Asp Lys Thr Thr Glu Arg Asp Leu Arg Thr Thr Pro 915 920 925 Glu Thr Thr Thr Ala Ala Pro Lys Met Thr Lys Glu Thr Ala Thr Thr 930 935 940 Thr Glu Lys Thr Thr Glu Ser Lys Ile Thr Ala Thr Thr Thr Gln Val 945 950 955 960 Thr Ser Thr Thr Thr Gln Asp Thr Thr Pro Phe Lys Ile Thr Thr Leu 965 970 975 Lys Thr Thr Thr Leu Ala Pro Lys Val Thr Thr Thr Lys Lys Thr Ile 980 985 990 Thr Thr Thr Glu Ile Met Asn Lys Pro Glu Glu Thr Ala Lys Pro Lys 995 1000 1005 Asp Arg Ala Thr Asn Ser Lys Ala Thr Thr Pro Lys Pro Gln Lys Pro 1010 1015 1020 Thr Lys Ala Pro Lys Lys Pro Thr Ser Thr Lys Lys Pro Lys Thr Met 1025 1030 1035 1040 Pro Arg Val Arg Lys Pro Lys Thr Thr Pro Thr Pro Arg Lys Met Thr 1045 1050 1055 Ser Thr Met Pro Glu Leu Asn Pro Thr Ser Arg Ile Ala Glu Ala Met 1060 1065 1070 Leu Gln Thr Thr Thr Arg Pro Asn Gln Thr Pro Asn Ser Lys Leu Val 1075 1080 1085 Glu Val Asn Pro Lys Ser Glu Asp Ala Gly Gly Ala Glu Gly Glu Thr 1090 1095 1100 Pro His Met Leu Leu Arg Pro His Val Phe Met Pro Glu Val Thr Pro 1105 1110 1115 1120 Asp Met Asp Tyr Leu Pro Arg Val Pro Asn Gln Gly Ile Ile Ile Asn 1125 1130 1135 Pro Met Leu Ser Asp Glu Thr Asn Ile Cys Asn Gly Lys Pro Val Asp 1140 1145 1150 Gly Leu Thr Thr Leu Arg Asn Gly Thr Leu Val Ala Phe Arg Gly His 1155 1160 1165 Tyr Phe Trp Met Leu Ser Pro Phe Ser Pro Pro Ser Pro Ala Arg Arg 1170 1175 1180 Ile Thr Glu Val Trp Gly Ile Pro Ser Pro Ile Asp Thr Val Phe Thr 1185 1190 1195 1200 Arg Cys Asn Cys Glu Gly Lys Thr Phe Phe Phe Lys Asp Ser Gln Tyr 1205 1210 1215 Trp Arg Phe Thr Asn Asp Ile Lys Asp Ala Gly Tyr Pro Lys Pro Ile 1220 1225 1230 Phe Lys Gly Phe Gly Gly Leu Thr Gly Gln Ile Val Ala Ala Leu Ser 1235 1240 1245 Thr Ala Lys Tyr Lys Asn Trp Pro Glu Ser Val Tyr Phe Phe Lys Arg 1250 1255 1260 Gly Gly Ser Ile Gln Gln Tyr Ile Tyr Lys Gln Glu Pro Val Gln Lys 1265 1270 1275 1280 Cys Pro Gly Arg Arg Pro Ala Leu Asn Tyr Pro Val Tyr Gly Glu Thr 1285 1290 1295 Thr Gln Val Arg Arg Arg Arg Phe Glu Arg Ala Ile Gly Pro Ser Gln 1300 1305 1310 Thr His Thr Ile Arg Ile Gln Tyr Ser Pro Ala Arg Leu Ala Tyr Gln 1315 1320 1325 Asp Lys Gly Val Leu His Asn Glu Val Lys Val Ser Ile Leu Trp Arg 1330 1335 1340 Gly Leu Pro Asn Val Val Thr Ser Ala Ile Ser Leu Pro Asn Ile Arg 1345 1350 1355 1360 Lys Pro Asp Gly Tyr Asp Tyr Tyr Ala Phe Ser Lys Asp Gln Tyr Tyr 1365 1370 1375 Asn Ile Asp Val Pro Ser Arg Thr Ala Arg Ala Ile Thr Thr Arg Ser 1380 1385 1390 Gly Gln Thr Leu Ser Lys Val Trp Tyr Asn Cys Pro 1395 1400 <210> 48 <211> 427 <212> PRT <213> Homo sapiens <400> 48 Met His Leu Ile Asp Tyr Leu Leu Leu Leu Leu Val Gly Leu Leu Ala 1 5 10 15 Leu Ser His Gly Gln Leu His Val Glu His Asp Gly Glu Ser Cys Ser 20 25 30 Asn Ser Ser His Gln Gln Ile Leu Glu Thr Gly Glu Gly Ser Pro Ser 35 40 45 Leu Lys Ile Ala Pro Ala Asn Ala Asp Phe Ala Phe Arg Phe Tyr Tyr 50 55 60 Leu Ile Ala Ser Glu Thr Pro Gly Lys Asn Ile Phe Phe Ser Pro Leu 65 70 75 80 Ser Ile Ser Ala Ala Tyr Ala Met Leu Ser Leu Gly Ala Cys Ser His 85 90 95 Ser Arg Ser Gln Ile Leu Glu Gly Leu Gly Phe Asn Leu Thr Glu Leu 100 105 110 Ser Glu Ser Asp Val His Arg Gly Phe Gln His Leu Leu His Thr Leu 115 120 125 Asn Leu Pro Gly His Gly Leu Glu Thr Arg Val Gly Ser Ala Leu Phe 130 135 140 Leu Ser His Asn Leu Lys Phe Leu Ala Lys Phe Leu Asn Asp Thr Met 145 150 155 160 Ala Val Tyr Glu Ala Lys Leu Phe His Thr Asn Phe Tyr Asp Thr Val 165 170 175 Gly Thr Ile Gln Leu Ile Asn Asp His Val Lys Lys Glu Thr Arg Gly 180 185 190 Lys Ile Val Asp Leu Val Ser Glu Leu Lys Lys Asp Val Leu Met Val 195 200 205 Leu Val Asn Tyr Ile Tyr Phe Lys Ala Leu Trp Glu Lys Pro Phe Ile 210 215 220 Ser Ser Arg Thr Thr Pro Lys Asp Phe Tyr Val Asp Glu Asn Thr Thr 225 230 235 240 Val Arg Val Pro Met Met Leu Gln Asp Gln Glu His His Trp Tyr Leu 245 250 255 His Asp Arg Tyr Leu Pro Cys Ser Val Leu Arg Met Asp Tyr Lys Gly 260 265 270 Asp Ala Thr Val Phe Phe Ile Leu Pro Asn Gln Gly Lys Met Arg Glu 275 280 285 Ile Glu Glu Val Leu Thr Pro Glu Met Leu Met Arg Trp Asn Asn Leu 290 295 300 Leu Arg Lys Arg Asn Phe Tyr Lys Lys Leu Glu Leu His Leu Pro Lys 305 310 315 320 Phe Ser Ile Ser Gly Ser Tyr Val Leu Asp Gln Ile Leu Pro Arg Leu 325 330 335 Gly Phe Thr Asp Leu Phe Ser Lys Trp Ala Asp Leu Ser Gly Ile Thr 340 345 350 Lys Gln Gln Lys Leu Glu Ala Ser Lys Ser Phe His Lys Ala Thr Leu 355 360 365 Asp Val Asp Glu Ala Gly Thr Glu Ala Ala Ala Ala Thr Ser Phe Ala 370 375 380 Ile Lys Phe Phe Ser Ala Gln Thr Asn Arg His Ile Leu Arg Phe Asn 385 390 395 400 Arg Pro Phe Leu Val Val Ile Phe Ser Thr Ser Thr Gln Ser Val Leu 405 410 415 Phe Leu Gly Lys Val Val Asp Pro Thr Lys Pro 420 425 <210> 49 <211> 481 <212> PRT <213> Homo sapiens <400> 49 Met Gly Ala Leu Ala Arg Ala Leu Pro Ser Ile Leu Leu Ala Leu Leu 1 5 10 15 Leu Thr Ser Thr Pro Glu Ala Leu Gly Ala Asn Pro Gly Leu Val Ala 20 25 30 Arg Ile Thr Asp Lys Gly Leu Gln Tyr Ala Ala Gln Glu Gly Leu Leu 35 40 45 Ala Leu Gln Ser Glu Leu Leu Arg Ile Thr Leu Pro Asp Phe Thr Gly 50 55 60 Asp Leu Arg Ile Pro His Val Gly Arg Gly Arg Tyr Glu Phe His Ser 65 70 75 80 Leu Asn Ile His Ser Cys Glu Leu Leu His Ser Ala Leu Arg Pro Val 85 90 95 Pro Gly Gln Gly Leu Ser Leu Ser Ile Ser Asp Ser Ser Ile Arg Val 100 105 110 Gln Gly Arg Trp Lys Val Arg Lys Ser Phe Phe Lys Leu Gln Gly Ser 115 120 125 Phe Asp Val Ser Val Lys Gly Ile Ser Ile Ser Val Asn Leu Leu Leu 130 135 140 Gly Ser Glu Ser Ser Gly Arg Pro Thr Val Thr Ala Ser Ser Cys Ser 145 150 155 160 Ser Asp Ile Ala Asp Val Glu Val Asp Met Ser Gly Asp Leu Gly Trp 165 170 175 Leu Leu Asn Leu Phe His Asn Gln Ile Glu Ser Lys Phe Gln Lys Val 180 185 190 Leu Glu Ser Arg Ile Cys Glu Met Ile Gln Lys Ser Val Ser Ser Asp 195 200 205 Leu Gln Pro Tyr Leu Gln Thr Leu Pro Val Thr Thr Glu Ile Asp Ser 210 215 220 Phe Ala Asp Ile Asp Tyr Ser Leu Val Glu Ala Pro Arg Ala Thr Ala 225 230 235 240 Gln Met Leu Glu Val Met Phe Lys Gly Glu Ile Phe His Arg Asn His 245 250 255 Arg Ser Pro Val Thr Leu Leu Ala Ala Val Met Ser Leu Pro Glu Glu 260 265 270 His Asn Lys Met Val Tyr Phe Ala Ile Ser Asp Tyr Val Phe Asn Thr 275 280 285 Ala Ser Leu Val Tyr His Glu Glu Gly Tyr Leu Asn Phe Ser Ile Thr 290 295 300 Asp Asp Met Ile Pro Pro Asp Ser Asn Ile Arg Leu Thr Thr Lys Ser 305 310 315 320 Phe Arg Pro Phe Val Pro Arg Leu Ala Arg Leu Tyr Pro Asn Met Asn 325 330 335 Leu Glu Leu Gln Gly Ser Val Pro Ser Ala Pro Leu Leu Asn Phe Ser 340 345 350 Pro Gly Asn Leu Ser Val Asp Pro Tyr Met Glu Ile Asp Ala Phe Val 355 360 365 Leu Leu Pro Ser Ser Ser Lys Glu Pro Val Phe Arg Leu Ser Val Ala 370 375 380 Thr Asn Val Ser Ala Thr Leu Thr Phe Asn Thr Ser Lys Ile Thr Gly 385 390 395 400 Phe Leu Lys Pro Gly Lys Val Lys Val Glu Leu Lys Glu Ser Lys Val 405 410 415 Gly Leu Phe Asn Ala Glu Leu Leu Glu Ala Leu Leu Asn Tyr Tyr Ile 420 425 430 Leu Asn Thr Phe Tyr Pro Lys Phe Asn Asp Lys Leu Ala Glu Gly Phe 435 440 445 Pro Leu Pro Leu Leu Lys Arg Val Gln Leu Tyr Asp Leu Gly Leu Gln 450 455 460 Ile His Lys Asp Phe Leu Phe Leu Gly Ala Asn Val Gln Tyr Met Arg 465 470 475 480 Val <210> 50 <211> 166 <212> PRT <213> Homo sapiens <400> 50 Met Ala Gln Thr Ser Ser Tyr Phe Met Leu Ile Ser Cys Leu Met Phe 1 5 10 15 Leu Ser Gln Ser Gln Gly Gln Glu Ala Gln Thr Glu Leu Pro Gln Ala 20 25 30 Arg Ile Ser Cys Pro Glu Gly Thr Asn Ala Tyr Arg Ser Tyr Cys Tyr 35 40 45 Tyr Phe Asn Glu Asp Arg Glu Thr Trp Val Asp Ala Asp Leu Tyr Cys 50 55 60 Gln Asn Met Asn Ser Gly Asn Leu Val Ser Val Leu Thr Gln Ala Glu 65 70 75 80 Gly Ala Phe Val Ala Ser Leu Ile Lys Glu Ser Gly Thr Asp Asp Phe 85 90 95 Asn Val Trp Ile Gly Leu His Asp Pro Lys Lys Asn Arg Arg Trp His 100 105 110 Trp Ser Ser Gly Ser Leu Val Ser Tyr Lys Ser Trp Gly Ile Gly Ala 115 120 125 Pro Ser Ser Val Asn Pro Gly Tyr Cys Val Ser Leu Thr Ser Ser Thr 130 135 140 Gly Phe Gln Lys Trp Lys Asp Val Pro Cys Glu Asp Lys Phe Ser Phe 145 150 155 160 Val Cys Lys Phe Lys Asn 165 <210> 51 <211> 972 <212> PRT <213> Homo sapiens <400> 51 Met Gly Pro Gly Val Leu Leu Leu Leu Leu Val Ala Thr Ala Trp His 1 5 10 15 Gly Gln Gly Ile Pro Val Ile Glu Pro Ser Val Pro Glu Leu Val Val 20 25 30 Lys Pro Gly Ala Thr Val Thr Leu Arg Cys Val Gly Asn Gly Ser Val 35 40 45 Glu Trp Asp Gly Pro Pro Ser Pro His Trp Thr Leu Tyr Ser Asp Gly 50 55 60 Ser Ser Ser Ile Leu Ser Thr Asn Asn Ala Thr Phe Gln Asn Thr Gly 65 70 75 80 Thr Tyr Arg Cys Thr Glu Pro Gly Asp Pro Leu Gly Gly Ser Ala Ala 85 90 95 Ile His Leu Tyr Val Lys Asp Pro Ala Arg Pro Trp Asn Val Leu Ala 100 105 110 Gln Glu Val Val Val Phe Glu Asp Gln Asp Ala Leu Leu Pro Cys Leu 115 120 125 Leu Thr Asp Pro Val Leu Glu Ala Gly Val Ser Leu Val Arg Val Arg 130 135 140 Gly Arg Pro Leu Met Arg His Thr Asn Tyr Ser Phe Ser Pro Trp His 145 150 155 160 Gly Phe Thr Ile His Arg Ala Lys Phe Ile Gln Ser Gln Asp Tyr Gln 165 170 175 Cys Ser Ala Leu Met Gly Gly Arg Lys Val Met Ser Ile Ser Ile Arg 180 185 190 Leu Lys Val Gln Lys Val Ile Pro Gly Pro Pro Ala Leu Thr Leu Val 195 200 205 Pro Ala Glu Leu Val Arg Ile Arg Gly Glu Ala Ala Gln Ile Val Cys 210 215 220 Ser Ala Ser Ser Val Asp Val Asn Phe Asp Val Phe Leu Gln His Asn 225 230 235 240 Asn Thr Lys Leu Ala Ile Pro Gln Gln Ser Asp Phe His Asn Asn Arg 245 250 255 Tyr Gln Lys Val Leu Thr Leu Asn Leu Asp Gln Val Asp Phe Gln His 260 265 270 Ala Gly Asn Tyr Ser Cys Val Ala Ser Asn Val Gln Gly Lys His Ser 275 280 285 Thr Ser Met Phe Phe Arg Val Val Glu Ser Ala Tyr Leu Asn Leu Ser 290 295 300 Ser Glu Gln Asn Leu Ile Gln Glu Val Thr Val Gly Glu Gly Leu Asn 305 310 315 320 Leu Lys Val Met Val Glu Ala Tyr Pro Gly Leu Gln Gly Phe Asn Trp 325 330 335 Thr Tyr Leu Gly Pro Phe Ser Asp His Gln Pro Glu Pro Lys Leu Ala 340 345 350 Asn Ala Thr Thr Lys Asp Thr Tyr Arg His Thr Phe Thr Leu Ser Leu 355 360 365 Pro Arg Leu Lys Pro Ser Glu Ala Gly Arg Tyr Ser Phe Leu Ala Arg 370 375 380 Asn Pro Gly Gly Trp Arg Ala Leu Thr Phe Glu Leu Thr Leu Arg Tyr 385 390 395 400 Pro Pro Glu Val Ser Val Ile Trp Thr Phe Ile Asn Gly Ser Gly Thr 405 410 415 Leu Leu Cys Ala Ala Ser Gly Tyr Pro Gln Pro Asn Val Thr Trp Leu 420 425 430 Gln Cys Ser Gly His Thr Asp Arg Cys Asp Glu Ala Gln Val Leu Gln 435 440 445 Val Trp Asp Asp Pro Tyr Pro Glu Val Leu Ser Gln Glu Pro Phe His 450 455 460 Lys Val Thr Val Gln Ser Leu Leu Thr Val Glu Thr Leu Glu His Asn 465 470 475 480 Gln Thr Tyr Glu Cys Arg Ala His Asn Ser Val Gly Ser Gly Ser Trp 485 490 495 Ala Phe Ile Pro Ile Ser Ala Gly Ala His Thr His Pro Pro Asp Glu 500 505 510 Phe Leu Phe Thr Pro Val Val Val Ala Cys Met Ser Ile Met Ala Leu 515 520 525 Leu Leu Leu Leu Leu Leu Leu Leu Leu Tyr Lys Tyr Lys Gln Lys Pro 530 535 540 Lys Tyr Gln Val Arg Trp Lys Ile Ile Glu Ser Tyr Glu Gly Asn Ser 545 550 555 560 Tyr Thr Phe Ile Asp Pro Thr Gln Leu Pro Tyr Asn Glu Lys Trp Glu 565 570 575 Phe Pro Arg Asn Asn Leu Gln Phe Gly Lys Thr Leu Gly Ala Gly Ala 580 585 590 Phe Gly Lys Val Val Glu Ala Thr Ala Phe Gly Leu Gly Lys Glu Asp 595 600 605 Ala Val Leu Lys Val Ala Val Lys Met Leu Lys Ser Thr Ala His Ala 610 615 620 Asp Glu Lys Glu Ala Leu Met Ser Glu Leu Lys Ile Met Ser His Leu 625 630 635 640 Gly Gln His Glu Asn Ile Val Asn Leu Leu Gly Ala Cys Thr His Gly 645 650 655 Gly Pro Val Leu Val Ile Thr Glu Tyr Cys Cys Tyr Gly Asp Leu Leu 660 665 670 Asn Phe Leu Arg Arg Lys Ala Glu Ala Met Leu Gly Pro Ser Leu Ser 675 680 685 Pro Gly Gln Asp Pro Glu Gly Gly Val Asp Tyr Lys Asn Ile His Leu 690 695 700 Glu Lys Lys Tyr Val Arg Arg Asp Ser Gly Phe Ser Ser Gln Gly Val 705 710 715 720 Asp Thr Tyr Val Glu Met Arg Pro Val Ser Thr Ser Ser Asn Asp Ser 725 730 735 Phe Ser Glu Gln Asp Leu Asp Lys Glu Asp Gly Arg Pro Leu Glu Leu 740 745 750 Arg Asp Leu Leu His Phe Ser Ser Gln Val Ala Gln Gly Met Ala Phe 755 760 765 Leu Ala Ser Lys Asn Cys Ile His Arg Asp Val Ala Ala Arg Asn Val 770 775 780 Leu Leu Thr Asn Gly His Val Ala Lys Ile Gly Asp Phe Gly Leu Ala 785 790 795 800 Arg Asp Ile Met Asn Asp Ser Asn Tyr Ile Val Lys Gly Asn Ala Arg 805 810 815 Leu Pro Val Lys Trp Met Ala Pro Glu Ser Ile Phe Asp Cys Val Tyr 820 825 830 Thr Val Gln Ser Asp Val Trp Ser Tyr Gly Ile Leu Leu Trp Glu Ile 835 840 845 Phe Ser Leu Gly Leu Asn Pro Tyr Pro Gly Ile Leu Val Asn Ser Lys 850 855 860 Phe Tyr Lys Leu Val Lys Asp Gly Tyr Gln Met Ala Gln Pro Ala Phe 865 870 875 880 Ala Pro Lys Asn Ile Tyr Ser Ile Met Gln Ala Cys Trp Ala Leu Glu 885 890 895 Pro Thr His Arg Pro Thr Phe Gln Gln Ile Cys Ser Phe Leu Gln Glu 900 905 910 Gln Ala Gln Glu Asp Arg Arg Glu Arg Asp Tyr Thr Asn Leu Pro Ser 915 920 925 Ser Ser Arg Ser Gly Gly Ser Gly Ser Ser Ser Ser Glu Leu Glu Glu 930 935 940 Glu Ser Ser Ser Glu His Leu Thr Cys Cys Glu Gln Gly Asp Ile Ala 945 950 955 960 Gln Pro Leu Leu Gln Pro Asn Asn Tyr Gln Phe Cys 965 970 <210> 52 <211> 298 <212> PRT <213> Homo sapiens <400> 52 Met Lys Thr Leu Gln Ser Thr Leu Leu Leu Leu Leu Leu Val Pro Leu 1 5 10 15 Ile Lys Pro Ala Pro Pro Thr Gln Gln Asp Ser Arg Ile Ile Tyr Asp 20 25 30 Tyr Gly Thr Asp Asn Phe Glu Glu Ser Ile Phe Ser Gln Asp Tyr Glu 35 40 45 Asp Lys Tyr Leu Asp Gly Lys Asn Ile Lys Glu Lys Glu Thr Val Ile 50 55 60 Ile Pro Asn Glu Lys Ser Leu Gln Leu Gln Lys Asp Glu Ala Ile Thr 65 70 75 80 Pro Leu Pro Pro Lys Lys Glu Asn Asp Glu Met Pro Thr Cys Leu Leu 85 90 95 Cys Val Cys Leu Ser Gly Ser Val Tyr Cys Glu Glu Val Asp Ile Asp 100 105 110 Ala Val Pro Pro Leu Pro Lys Glu Ser Ala Tyr Leu Tyr Ala Arg Phe 115 120 125 Asn Lys Ile Lys Lys Leu Thr Ala Lys Asp Phe Ala Asp Ile Pro Asn 130 135 140 Leu Arg Arg Leu Asp Phe Thr Gly Asn Leu Ile Glu Asp Ile Glu Asp 145 150 155 160 Gly Thr Phe Ser Lys Leu Ser Leu Leu Glu Glu Leu Ser Leu Ala Glu 165 170 175 Asn Gln Leu Leu Lys Leu Pro Val Leu Pro Pro Lys Leu Thr Leu Phe 180 185 190 Asn Ala Lys Tyr Asn Lys Ile Lys Ser Arg Gly Ile Lys Ala Asn Ala 195 200 205 Phe Lys Lys Leu Asn Asn Leu Thr Phe Leu Tyr Leu Asp His Asn Ala 210 215 220 Leu Glu Ser Val Pro Leu Asn Leu Pro Glu Ser Leu Arg Val Ile His 225 230 235 240 Leu Gln Phe Asn Asn Ile Ala Ser Ile Thr Asp Asp Thr Phe Cys Lys 245 250 255 Ala Asn Asp Thr Ser Tyr Ile Arg Asp Arg Ile Glu Glu Ile Arg Leu 260 265 270 Glu Gly Asn Pro Ile Val Leu Gly Lys His Pro Asn Ser Phe Ile Cys 275 280 285 Leu Lys Arg Leu Pro Ile Gly Ser Tyr Phe 290 295 <210> 53 <211> 298 <212> PRT <213> Homo sapiens <400> 53 Met Lys Thr Leu Gln Ser Thr Leu Leu Leu Leu Leu Leu Val Pro Leu 1 5 10 15 Ile Lys Pro Ala Pro Pro Thr Gln Gln Asp Ser Arg Ile Ile Tyr Asp 20 25 30 Tyr Gly Thr Asp Asn Phe Glu Glu Ser Ile Phe Ser Gln Asp Tyr Glu 35 40 45 Asp Lys Tyr Leu Asp Gly Lys Asn Ile Lys Glu Lys Glu Thr Val Ile 50 55 60 Ile Pro Asn Glu Lys Ser Leu Gln Leu Gln Lys Asp Glu Ala Ile Thr 65 70 75 80 Pro Leu Pro Pro Lys Lys Glu Asn Asp Glu Met Pro Thr Cys Leu Leu 85 90 95 Cys Val Cys Leu Ser Gly Ser Val Tyr Cys Glu Glu Val Asp Ile Asp 100 105 110 Ala Val Pro Pro Leu Pro Lys Glu Ser Ala Tyr Leu Tyr Ala Arg Phe 115 120 125 Asn Lys Ile Lys Lys Leu Thr Ala Lys Asp Phe Ala Asp Ile Pro Asn 130 135 140 Leu Arg Arg Leu Asp Phe Thr Gly Asn Leu Ile Glu Asp Ile Glu Asp 145 150 155 160 Gly Thr Phe Ser Lys Leu Ser Leu Leu Glu Glu Leu Ser Leu Ala Glu 165 170 175 Asn Gln Leu Leu Lys Leu Pro Val Leu Pro Pro Lys Leu Thr Leu Phe 180 185 190 Asn Ala Lys Tyr Asn Lys Ile Lys Ser Arg Gly Ile Lys Ala Asn Ala 195 200 205 Phe Lys Lys Leu Asn Asn Leu Thr Phe Leu Tyr Leu Asp His Asn Ala 210 215 220 Leu Glu Ser Val Pro Leu Asn Leu Pro Glu Ser Leu Arg Val Ile His 225 230 235 240 Leu Gln Phe Asn Asn Ile Ala Ser Ile Thr Asp Asp Thr Phe Cys Lys 245 250 255 Ala Asn Asp Thr Ser Tyr Ile Arg Asp Arg Ile Glu Glu Ile Arg Leu 260 265 270 Glu Gly Asn Pro Ile Val Leu Gly Lys His Pro Asn Ser Phe Ile Cys 275 280 285 Leu Lys Arg Leu Pro Ile Gly Ser Tyr Phe 290 295 <210> 54 <211> 5205 <212> PRT <213> Homo sapiens <400> 54 Met Gly Ala Pro Ser Ala Cys Arg Thr Leu Val Leu Ala Leu Ala Ala 1 5 10 15 Met Leu Val Val Pro Gln Ala Glu Thr Gln Gly Pro Val Glu Pro Ser 20 25 30 Trp Glu Asn Ala Gly His Thr Met Asp Gly Gly Ala Pro Thr Ser Ser 35 40 45 Pro Thr Arg Arg Val Ser Phe Val Pro Pro Val Thr Val Phe Pro Ser 50 55 60 Leu Ser Pro Leu Asn Pro Ala His Asn Gly Arg Val Cys Ser Thr Trp 65 70 75 80 Gly Asp Phe His Tyr Lys Thr Phe Asp Gly Asp Val Phe Arg Phe Pro 85 90 95 Gly Leu Cys Asn Tyr Val Phe Ser Glu His Cys Arg Ala Ala Tyr Glu 100 105 110 Asp Phe Asn Val Gln Leu Arg Arg Gly Leu Val Gly Ser Arg Pro Val 115 120 125 Val Thr Arg Val Val Ile Lys Ala Gln Gly Leu Val Leu Glu Ala Ser 130 135 140 Asn Gly Ser Val Leu Ile Asn Gly Gln Arg Glu Glu Leu Pro Tyr Ser 145 150 155 160 Arg Thr Gly Leu Leu Val Glu Gln Ser Gly Asp Tyr Ile Lys Val Ser 165 170 175 Ile Arg Leu Val Leu Thr Phe Leu Trp Asn Gly Glu Asp Ser Ala Leu 180 185 190 Leu Glu Leu Asp Pro Lys Tyr Ala Asn Gln Thr Cys Gly Leu Cys Gly 195 200 205 Asp Phe Asn Gly Leu Pro Ala Phe Asn Glu Phe Tyr Ala His Asn Ala 210 215 220 Arg Leu Thr Pro Leu Gln Phe Gly Asn Leu Gln Lys Leu Asp Gly Pro 225 230 235 240 Thr Glu Gln Cys Pro Asp Pro Leu Pro Leu Pro Ala Gly Asn Cys Thr 245 250 255 Asp Glu Glu Gly Ile Cys His Arg Thr Leu Leu Gly Pro Ala Phe Ala 260 265 270 Glu Cys His Ala Leu Val Asp Ser Thr Ala Tyr Leu Ala Ala Cys Ala 275 280 285 Gln Asp Leu Cys Arg Cys Pro Thr Cys Pro Cys Ala Thr Phe Val Glu 290 295 300 Tyr Ser Arg Gln Cys Ala His Ala Gly Gly Gln Pro Arg Asn Trp Arg 305 310 315 320 Cys Pro Glu Leu Cys Pro Arg Thr Cys Pro Leu Asn Met Gln His Gln 325 330 335 Glu Cys Gly Ser Pro Cys Thr Asp Thr Cys Ser Asn Pro Gln Arg Ala 340 345 350 Gln Leu Cys Glu Asp His Cys Val Asp Gly Cys Phe Cys Pro Pro Gly 355 360 365 Thr Val Leu Asp Asp Ile Thr His Ser Gly Cys Leu Pro Leu Gly Gln 370 375 380 Cys Pro Cys Thr His Gly Gly Arg Thr Tyr Ser Pro Gly Thr Ser Phe 385 390 395 400 Asn Thr Thr Cys Ser Ser Cys Thr Cys Ser Gly Gly Leu Trp Gln Cys 405 410 415 Gln Asp Leu Pro Cys Pro Gly Thr Cys Ser Val Gln Gly Gly Ala His 420 425 430 Ile Ser Thr Tyr Asp Glu Lys Leu Tyr Asp Leu His Gly Asp Cys Ser 435 440 445 Tyr Val Leu Ser Lys Lys Cys Ala Asp Ser Ser Phe Thr Val Leu Ala 450 455 460 Glu Leu Arg Lys Cys Gly Leu Thr Asp Asn Glu Asn Cys Leu Lys Ala 465 470 475 480 Val Thr Leu Ser Leu Asp Gly Gly Asp Thr Ala Ile Arg Val Gln Ala 485 490 495 Asp Gly Gly Val Phe Leu Asn Ser Ile Tyr Thr Gln Leu Pro Leu Ser 500 505 510 Ala Ala Asn Ile Thr Leu Phe Thr Pro Ser Ser Phe Phe Ile Val Val 515 520 525 Gln Thr Gly Leu Gly Leu Gln Leu Leu Val Gln Leu Val Pro Leu Met 530 535 540 Gln Val Phe Val Arg Leu Asp Pro Ala His Gln Gly Gln Met Cys Gly 545 550 555 560 Leu Cys Gly Asn Phe Asn Gln Asn Gln Ala Asp Asp Phe Thr Ala Leu 565 570 575 Ser Gly Val Val Glu Ala Thr Gly Ala Ala Phe Ala Asn Thr Trp Lys 580 585 590 Ala Gln Ala Ala Cys Ala Asn Ala Arg Asn Ser Phe Glu Asp Pro Cys 595 600 605 Ser Leu Ser Val Glu Asn Glu Asn Tyr Ala Arg His Trp Cys Ser Arg 610 615 620 Leu Thr Asp Pro Asn Ser Ala Phe Ser Arg Cys His Ser Ile Ile Asn 625 630 635 640 Pro Lys Pro Phe His Ser Asn Cys Met Phe Asp Thr Cys Asn Cys Glu 645 650 655 Arg Ser Glu Asp Cys Leu Cys Ala Ala Leu Ser Ser Tyr Val His Ala 660 665 670 Cys Ala Ala Lys Gly Val Gln Leu Ser Asp Trp Arg Asp Gly Val Cys 675 680 685 Thr Lys Tyr Met Gln Asn Cys Pro Lys Ser Gln Arg Tyr Ala Tyr Val 690 695 700 Val Asp Ala Cys Gln Pro Thr Cys Arg Gly Leu Ser Glu Ala Asp Val 705 710 715 720 Thr Cys Ser Val Ser Phe Val Pro Val Asp Gly Cys Thr Cys Pro Ala 725 730 735 Gly Thr Phe Leu Asn Asp Ala Gly Ala Cys Val Pro Ala Gln Glu Cys 740 745 750 Pro Cys Tyr Ala His Gly Thr Val Leu Ala Pro Gly Glu Val Val His 755 760 765 Asp Glu Gly Ala Val Cys Ser Cys Thr Gly Gly Lys Leu Ser Cys Leu 770 775 780 Gly Ala Ser Leu Gln Lys Ser Thr Gly Cys Ala Ala Pro Met Val Tyr 785 790 795 800 Leu Asp Cys Ser Asn Ser Ser Ala Gly Thr Pro Gly Ala Glu Cys Leu 805 810 815 Arg Ser Cys His Thr Leu Asp Val Gly Cys Phe Ser Thr His Cys Val 820 825 830 Ser Gly Cys Val Cys Pro Pro Gly Leu Val Ser Asp Gly Ser Gly Gly 835 840 845 Cys Ile Ala Glu Glu Asp Cys Pro Cys Val His Asn Glu Ala Thr Tyr 850 855 860 Lys Pro Gly Glu Thr Ile Arg Val Asp Cys Asn Thr Cys Thr Cys Arg 865 870 875 880 Asn Arg Arg Trp Glu Cys Ser His Arg Leu Cys Leu Gly Thr Cys Val 885 890 895 Ala Tyr Gly Asp Gly His Phe Ile Thr Phe Asp Gly Asp Arg Tyr Ser 900 905 910 Phe Glu Gly Ser Cys Glu Tyr Ile Leu Ala Gln Asp Tyr Cys Gly Asp 915 920 925 Asn Thr Thr His Gly Thr Phe Arg Ile Val Thr Glu Asn Ile Pro Cys 930 935 940 Gly Thr Thr Gly Thr Thr Cys Ser Lys Ala Ile Lys Leu Phe Val Glu 945 950 955 960 Ser Tyr Glu Leu Ile Leu Gln Glu Gly Thr Phe Lys Ala Val Ala Arg 965 970 975 Gly Pro Gly Gly Asp Pro Pro Tyr Lys Ile Arg Tyr Met Gly Ile Phe 980 985 990 Leu Val Ile Glu Thr His Gly Met Ala Val Ser Trp Asp Arg Lys Thr 995 1000 1005 Ser Val Phe Ile Arg Leu His Gln Asp Tyr Lys Gly Arg Val Cys Gly 1010 1015 1020 Leu Cys Gly Asn Phe Asp Asp Asn Ala Ile Asn Asp Phe Ala Thr Arg 1025 1030 1035 1040 Ser Arg Ser Val Val Gly Asp Ala Leu Glu Phe Gly Asn Ser Trp Lys 1045 1050 1055 Leu Ser Pro Ser Cys Pro Asp Ala Leu Ala Pro Lys Asp Pro Cys Thr 1060 1065 1070 Ala Asn Pro Phe Arg Lys Ser Trp Ala Gln Lys Gln Cys Ser Ile Leu 1075 1080 1085 His Gly Pro Thr Phe Ala Ala Cys Arg Ser Gln Val Asp Ser Thr Lys 1090 1095 1100 Tyr Tyr Glu Ala Cys Val Asn Asp Ala Cys Ala Cys Asp Ser Gly Gly 1105 1110 1115 1120 Asp Cys Glu Cys Phe Cys Thr Ala Val Ala Ala Tyr Ala Gln Ala Cys 1125 1130 1135 His Asp Ala Gly Leu Cys Val Ser Trp Arg Thr Pro Asp Thr Cys Pro 1140 1145 1150 Leu Phe Cys Asp Phe Tyr Asn Pro His Gly Gly Cys Glu Trp His Tyr 1155 1160 1165 Gln Pro Cys Gly Ala Pro Cys Leu Lys Thr Cys Arg Asn Pro Ser Gly 1170 1175 1180 His Cys Leu Val Asp Leu Pro Gly Leu Glu Gly Cys Tyr Pro Lys Cys 1185 1190 1195 1200 Pro Pro Ser Gln Pro Phe Phe Asn Glu Asp Gln Met Lys Cys Val Ala 1205 1210 1215 Gln Cys Gly Cys Tyr Asp Lys Asp Gly Asn Tyr Tyr Asp Val Gly Ala 1220 1225 1230 Arg Val Pro Thr Ala Glu Asn Cys Gln Ser Cys Asn Cys Thr Pro Ser 1235 1240 1245 Gly Ile Gln Cys Ala His Ser Leu Glu Ala Cys Thr Cys Thr Tyr Glu 1250 1255 1260 Asp Arg Thr Tyr Ser Tyr Gln Asp Val Ile Tyr Asn Thr Thr Asp Gly 1265 1270 1275 1280 Leu Gly Ala Cys Leu Ile Ala Ile Cys Gly Ser Asn Gly Thr Ile Ile 1285 1290 1295 Arg Lys Ala Val Ala Cys Pro Gly Thr Pro Ala Thr Thr Pro Phe Thr 1300 1305 1310 Phe Thr Thr Ala Trp Val Pro His Ser Thr Thr Ser Pro Ala Leu Pro 1315 1320 1325 Val Ser Thr Val Cys Val Arg Glu Val Cys Arg Trp Ser Ser Trp Tyr 1330 1335 1340 Asn Gly His Arg Pro Glu Pro Gly Leu Gly Gly Gly Asp Phe Glu Thr 1345 1350 1355 1360 Phe Glu Asn Leu Arg Gln Arg Gly Tyr Gln Val Cys Pro Val Leu Ala 1365 1370 1375 Asp Ile Glu Cys Arg Ala Ala Gln Leu Pro Asp Met Pro Leu Glu Glu 1380 1385 1390 Leu Gly Gln Gln Val Asp Cys Asp Arg Met Arg Gly Leu Met Cys Ala 1395 1400 1405 Asn Ser Gln Gln Ser Pro Pro Leu Cys His Asp Tyr Glu Leu Arg Val 1410 1415 1420 Leu Cys Cys Glu Tyr Val Pro Cys Gly Pro Ser Pro Ala Pro Gly Thr 1425 1430 1435 1440 Ser Pro Gln Pro Ser Leu Ser Ala Ser Thr Glu Pro Ala Val Pro Thr 1445 1450 1455 Pro Thr Gln Thr Thr Ala Thr Glu Lys Thr Thr Leu Trp Val Thr Pro 1460 1465 1470 Ser Ile Arg Ser Thr Ala Ala Leu Thr Ser Gln Thr Gly Ser Ser Ser 1475 1480 1485 Gly Pro Val Thr Val Thr Pro Ser Ala Pro Gly Thr Thr Thr Cys Gln 1490 1495 1500 Pro Arg Cys Gln Trp Thr Glu Trp Phe Asp Glu Asp Tyr Pro Lys Ser 1505 1510 1515 1520 Glu Gln Leu Gly Gly Asp Val Glu Ser Tyr Asp Lys Ile Arg Ala Ala 1525 1530 1535 Gly Gly His Leu Cys Gln Gln Pro Lys Asp Ile Glu Cys Gln Ala Glu 1540 1545 1550 Ser Phe Pro Asn Trp Thr Leu Ala Gln Val Gly Gln Lys Val His Cys 1555 1560 1565 Asp Val His Phe Gly Leu Val Cys Arg Asn Trp Glu Gln Glu Gly Val 1570 1575 1580 Phe Lys Met Cys Tyr Asn Tyr Arg Ile Arg Val Leu Cys Cys Ser Asp 1585 1590 1595 1600 Asp His Cys Arg Gly Arg Ala Thr Thr Pro Pro Pro Thr Thr Glu Leu 1605 1610 1615 Glu Thr Ala Thr Thr Thr Thr Thr Gln Ala Leu Phe Ser Thr Pro Gln 1620 1625 1630 Pro Thr Ser Ser Pro Gly Leu Thr Arg Ala Pro Pro Ala Ser Thr Thr 1635 1640 1645 Ala Val Pro Thr Leu Ser Glu Gly Leu Thr Ser Pro Arg Tyr Thr Ser 1650 1655 1660 Thr Leu Gly Thr Ala Thr Thr Gly Gly Pro Thr Thr Pro Ala Gly Ser 1665 1670 1675 1680 Thr Glu Pro Thr Val Pro Gly Val Ala Thr Ser Thr Leu Pro Thr Arg 1685 1690 1695 Ser Ala Leu Pro Gly Thr Thr Gly Ser Leu Gly Thr Trp Arg Pro Ser 1700 1705 1710 Gln Pro Pro Thr Leu Ala Pro Thr Thr Met Ala Thr Ser Arg Ala Arg 1715 1720 1725 Pro Thr Gly Thr Ala Ser Thr Ala Ser Lys Glu Pro Leu Thr Thr Ser 1730 1735 1740 Leu Ala Pro Thr Leu Thr Ser Glu Leu Ser Thr Ser Gln Ala Glu Thr 1745 1750 1755 1760 Ser Thr Pro Arg Thr Glu Thr Thr Met Ser Pro Leu Thr Asn Thr Thr 1765 1770 1775 Thr Ser Gln Gly Thr Thr Arg Cys Gln Pro Lys Cys Glu Trp Thr Glu 1780 1785 1790 Trp Phe Asp Val Asp Phe Pro Thr Ser Gly Val Ala Gly Gly Asp Met 1795 1800 1805 Glu Thr Phe Glu Asn Ile Arg Ala Ala Gly Gly Lys Met Cys Trp Ala 1810 1815 1820 Pro Lys Ser Ile Glu Cys Arg Ala Glu Asn Tyr Pro Glu Val Ser Ile 1825 1830 1835 1840 Asp Gln Val Gly Gln Val Leu Thr Cys Ser Leu Glu Thr Gly Leu Thr 1845 1850 1855 Cys Lys Asn Glu Asp Gln Thr Gly Arg Phe Asn Met Cys Phe Asn Tyr 1860 1865 1870 Asn Val Arg Val Leu Cys Cys Asp Asp Tyr Ser His Cys Pro Ser Thr 1875 1880 1885 Pro Ala Thr Ser Ser Thr Ala Thr Pro Ser Ser Thr Pro Gly Thr Thr 1890 1895 1900 Trp Ile Leu Thr Lys Pro Thr Thr Thr Ala Thr Thr Thr Ala Ser Thr 1905 1910 1915 1920 Gly Ser Thr Ala Thr Pro Thr Ser Thr Leu Arg Thr Ala Pro Pro Pro 1925 1930 1935 Lys Val Leu Thr Thr Thr Ala Thr Thr Pro Thr Val Thr Ser Ser Lys 1940 1945 1950 Ala Thr Pro Ser Ser Ser Pro Gly Thr Ala Thr Ala Leu Pro Ala Leu 1955 1960 1965 Arg Ser Thr Ala Thr Thr Pro Thr Ala Thr Ser Val Thr Pro Ile Pro 1970 1975 1980 Ser Ser Ser Leu Gly Thr Thr Trp Thr Arg Leu Ser Gln Thr Thr Thr 1985 1990 1995 2000 Pro Thr Ala Thr Met Ser Thr Ala Thr Pro Ser Ser Thr Pro Glu Thr 2005 2010 2015 Ala His Thr Ser Thr Val Leu Thr Thr Thr Ala Thr Thr Thr Gly Ala 2020 2025 2030 Thr Gly Ser Val Ala Thr Pro Ser Ser Thr Pro Gly Thr Ala His Thr 2035 2040 2045 Thr Lys Val Leu Thr Thr Thr Thr Thr Gly Phe Thr Ala Thr Pro Ser 2050 2055 2060 Ser Ser Pro Gly Arg Ala Arg Thr Leu Pro Val Trp Ile Ser Thr Thr 2065 2070 2075 2080 Thr Thr Pro Thr Thr Arg Gly Ser Thr Val Thr Pro Ser Ser Ile Pro 2085 2090 2095 Gly Thr Thr His Thr Pro Thr Val Leu Thr Thr Thr Thr Thr Thr Val 2100 2105 2110 Ala Thr Gly Ser Met Ala Thr Pro Ser Ser Ser Thr Gln Thr Ser Gly 2115 2120 2125 Thr Pro Pro Ser Leu Thr Thr Thr Ala Thr Thr Ile Thr Ala Thr Gly 2130 2135 2140 Ser Thr Thr Asn Pro Ser Ser Thr Pro Gly Thr Thr Pro Ile Pro Pro 2145 2150 2155 2160 Val Leu Thr Thr Thr Ala Thr Thr Pro Ala Ala Thr Ser Ser Thr Val 2165 2170 2175 Thr Pro Ser Ser Ala Leu Gly Thr Thr His Thr Pro Pro Val Pro Asn 2180 2185 2190 Thr Thr Ala Thr Thr His Gly Arg Ser Leu Ser Pro Ser Ser Pro His 2195 2200 2205 Thr Val Arg Thr Ala Trp Thr Ser Ala Thr Ser Gly Thr Leu Gly Thr 2210 2215 2220 Thr His Ile Thr Glu Pro Ser Thr Gly Thr Ser His Thr Pro Ala Ala 2225 2230 2235 2240 Thr Thr Gly Thr Thr Gln His Ser Thr Pro Ala Leu Ser Ser Pro His 2245 2250 2255 Pro Ser Ser Arg Thr Thr Glu Ser Pro Pro Ser Pro Gly Thr Thr Thr 2260 2265 2270 Pro Gly His Thr Arg Ala Thr Ser Arg Thr Thr Ala Thr Ala Thr Pro 2275 2280 2285 Ser Lys Thr Arg Thr Ser Thr Leu Leu Pro Ser Ser Pro Thr Ser Ala 2290 2295 2300 Pro Ile Thr Thr Val Val Thr Met Gly Cys Glu Pro Gln Cys Ala Trp 2305 2310 2315 2320 Ser Glu Trp Leu Asp Tyr Ser Tyr Pro Met Pro Gly Pro Ser Gly Gly 2325 2330 2335 Asp Phe Asp Thr Tyr Ser Asn Ile Arg Ala Ala Gly Gly Ala Val Cys 2340 2345 2350 Glu Gln Pro Leu Gly Leu Glu Cys Arg Ala Gln Ala Gln Pro Gly Val 2355 2360 2365 Pro Leu Arg Glu Leu Gly Gln Val Val Glu Cys Ser Leu Asp Phe Gly 2370 2375 2380 Leu Val Cys Arg Asn Arg Glu Gln Val Gly Lys Phe Lys Met Cys Phe 2385 2390 2395 2400 Asn Tyr Glu Ile Arg Val Phe Cys Cys Asn Tyr Gly His Cys Pro Ser 2405 2410 2415 Thr Pro Ala Thr Ser Ser Thr Ala Thr Pro Ser Ser Thr Pro Gly Thr 2420 2425 2430 Thr Trp Ile Leu Thr Glu Gln Thr Thr Ala Ala Thr Thr Thr Ala Thr 2435 2440 2445 Thr Gly Ser Thr Ala Ile Pro Ser Ser Thr Pro Gly Thr Ala Pro Pro 2450 2455 2460 Pro Lys Val Leu Thr Ser Thr Ala Thr Thr Pro Thr Ala Thr Ser Ser 2465 2470 2475 2480 Lys Ala Thr Ser Ser Ser Ser Pro Arg Thr Ala Thr Thr Leu Pro Val 2485 2490 2495 Leu Thr Ser Thr Ala Thr Lys Ser Thr Ala Thr Ser Phe Thr Pro Ile 2500 2505 2510 Pro Ser Phe Thr Leu Gly Thr Thr Gly Thr Leu Pro Glu Gln Thr Thr 2515 2520 2525 Thr Pro Met Ala Thr Met Ser Thr Ile His Pro Ser Ser Thr Pro Glu 2530 2535 2540 Thr Thr His Thr Ser Thr Val Leu Thr Thr Lys Ala Thr Thr Thr Arg 2545 2550 2555 2560 Ala Thr Ser Ser Met Ser Thr Pro Ser Ser Thr Pro Gly Thr Thr Trp 2565 2570 2575 Ile Leu Thr Glu Leu Thr Thr Ala Ala Thr Thr Thr Ala Ala Thr Gly 2580 2585 2590 Pro Thr Ala Thr Pro Ser Ser Thr Pro Gly Thr Thr Trp Ile Leu Thr 2595 2600 2605 Glu Pro Ser Thr Thr Ala Thr Val Thr Val Pro Thr Gly Ser Thr Ala 2610 2615 2620 Thr Ala Ser Ser Thr Arg Ala Thr Ala Gly Thr Leu Lys Val Leu Thr 2625 2630 2635 2640 Ser Thr Ala Thr Thr Pro Thr Val Ile Ser Ser Arg Ala Thr Pro Ser 2645 2650 2655 Ser Ser Pro Gly Thr Ala Thr Ala Leu Pro Ala Leu Arg Ser Thr Ala 2660 2665 2670 Thr Thr Pro Thr Ala Thr Ser Val Thr Ala Ile Pro Ser Ser Ser Leu 2675 2680 2685 Gly Thr Ala Trp Thr Arg Leu Ser Gln Thr Thr Thr Pro Thr Ala Thr 2690 2695 2700 Met Ser Thr Ala Thr Pro Ser Ser Thr Pro Glu Thr Val His Thr Ser 2705 2710 2715 2720 Thr Val Leu Thr Thr Thr Thr Thr Thr Thr Arg Ala Thr Gly Ser Val 2725 2730 2735 Ala Thr Pro Ser Ser Thr Pro Gly Thr Ala His Thr Thr Lys Val Pro 2740 2745 2750 Thr Thr Thr Thr Thr Gly Phe Thr Ala Thr Pro Ser Ser Ser Pro Gly 2755 2760 2765 Thr Ala Leu Thr Pro Pro Val Trp Ile Ser Thr Thr Thr Thr Pro Thr 2770 2775 2780 Thr Arg Gly Ser Thr Val Thr Pro Ser Ser Ile Pro Gly Thr Thr His 2785 2790 2795 2800 Thr Ala Thr Val Leu Thr Thr Thr Thr Thr Thr Val Ala Thr Gly Ser 2805 2810 2815 Met Ala Thr Pro Ser Ser Ser Thr Gln Thr Ser Gly Thr Pro Pro Ser 2820 2825 2830 Leu Thr Thr Thr Ala Thr Thr Ile Thr Ala Thr Gly Ser Thr Thr Asn 2835 2840 2845 Pro Ser Ser Thr Pro Gly Thr Thr Pro Ile Pro Pro Val Leu Thr Thr 2850 2855 2860 Thr Ala Thr Thr Pro Ala Ala Thr Ser Ser Thr Val Thr Pro Ser Ser 2865 2870 2875 2880 Ala Leu Gly Thr Thr His Thr Pro Pro Val Pro Asn Thr Met Ala Thr 2885 2890 2895 Thr His Gly Arg Ser Leu Pro Pro Ser Ser Pro His Thr Val Arg Thr 2900 2905 2910 Ala Trp Thr Ser Ala Thr Ser Gly Ile Leu Gly Thr Thr His Ile Thr 2915 2920 2925 Glu Pro Ser Thr Val Thr Ser His Thr Pro Ala Ala Thr Thr Gly Thr 2930 2935 2940 Thr Gln His Ser Thr Pro Ala Leu Ser Ser Pro His Pro Ser Ser Arg 2945 2950 2955 2960 Thr Thr Glu Ser Pro Pro Ser Pro Gly Thr Thr Thr Pro Gly His Thr 2965 2970 2975 Arg Gly Thr Ser Arg Thr Thr Ala Thr Ala Thr Pro Ser Lys Thr Arg 2980 2985 2990 Thr Ser Thr Leu Leu Pro Ser Ser Pro Thr Ser Ala Pro Ile Thr Thr 2995 3000 3005 Val Val Thr Met Gly Cys Glu Pro Gln Cys Ala Trp Ser Glu Trp Leu 3010 3015 3020 Asp Tyr Ser Tyr Pro Met Pro Gly Pro Ser Gly Gly Asp Phe Asp Thr 3025 3030 3035 3040 Tyr Ser Asn Ile Arg Ala Ala Gly Gly Ala Val Cys Glu Gln Pro Leu 3045 3050 3055 Gly Leu Glu Cys Arg Ala Gln Ala Gln Pro Gly Val Pro Leu Arg Glu 3060 3065 3070 Leu Gly Gln Val Val Glu Cys Ser Leu Asp Phe Gly Leu Val Cys Arg 3075 3080 3085 Asn Arg Glu Gln Val Gly Lys Phe Lys Met Cys Phe Asn Tyr Glu Ile 3090 3095 3100 Arg Val Phe Cys Cys Asn Tyr Gly His Cys Pro Ser Thr Pro Ala Thr 3105 3110 3115 3120 Ser Ser Thr Ala Met Pro Ser Ser Thr Pro Gly Thr Thr Trp Ile Leu 3125 3130 3135 Thr Glu Leu Thr Thr Thr Ala Thr Thr Thr Glu Ser Thr Gly Ser Thr 3140 3145 3150 Ala Thr Pro Ser Ser Thr Pro Gly Thr Thr Trp Ile Leu Thr Glu Pro 3155 3160 3165 Ser Thr Thr Ala Thr Val Thr Val Pro Thr Gly Ser Thr Ala Thr Ala 3170 3175 3180 Ser Ser Thr Gln Ala Thr Ala Gly Thr Pro His Val Ser Thr Thr Ala 3185 3190 3195 3200 Thr Thr Pro Thr Val Thr Ser Ser Lys Ala Thr Pro Phe Ser Ser Pro 3205 3210 3215 Gly Thr Ala Thr Ala Leu Pro Ala Leu Arg Ser Thr Ala Thr Thr Pro 3220 3225 3230 Thr Ala Thr Ser Phe Thr Ala Ile Pro Ser Ser Ser Leu Gly Thr Thr 3235 3240 3245 Trp Thr Arg Leu Ser Gln Thr Thr Thr Pro Thr Ala Thr Met Ser Thr 3250 3255 3260 Ala Thr Pro Ser Ser Thr Pro Glu Thr Ala His Thr Ser Thr Val Leu 3265 3270 3275 3280 Thr Thr Thr Ala Thr Thr Thr Arg Ala Thr Gly Ser Val Ala Thr Pro 3285 3290 3295 Ser Ser Thr Pro Gly Thr Ala His Thr Thr Lys Val Pro Thr Thr Thr 3300 3305 3310 Thr Thr Gly Phe Thr Val Thr Pro Ser Ser Ser Pro Gly Thr Ala Arg 3315 3320 3325 Thr Pro Pro Val Trp Ile Ser Thr Thr Thr Thr Pro Thr Thr Ser Gly 3330 3335 3340 Ser Thr Val Thr Pro Ser Ser Val Pro Gly Thr Thr His Thr Pro Thr 3345 3350 3355 3360 Val Leu Thr Thr Thr Thr Thr Thr Val Ala Thr Gly Ser Met Ala Thr 3365 3370 3375 Pro Ser Ser Ser Thr Gln Thr Ser Gly Thr Pro Pro Ser Leu Ile Thr 3380 3385 3390 Thr Ala Thr Thr Ile Thr Ala Thr Gly Ser Thr Thr Asn Pro Ser Ser 3395 3400 3405 Thr Pro Gly Thr Thr Pro Ile Pro Pro Val Leu Thr Thr Thr Ala Thr 3410 3415 3420 Thr Pro Ala Ala Thr Ser Ser Thr Val Thr Pro Ser Ser Ala Leu Gly 3425 3430 3435 3440 Thr Thr His Thr Pro Pro Val Pro Asn Thr Thr Ala Thr Thr His Gly 3445 3450 3455 Arg Ser Leu Ser Pro Ser Ser Pro His Thr Val Arg Thr Ala Trp Thr 3460 3465 3470 Ser Ala Thr Ser Gly Thr Leu Gly Thr Thr His Ile Thr Glu Pro Ser 3475 3480 3485 Thr Gly Thr Ser His Thr Pro Ala Ala Thr Thr Gly Thr Thr Gln His 3490 3495 3500 Ser Thr Pro Ala Leu Ser Ser Pro His Pro Ser Ser Arg Thr Thr Glu 3505 3510 3515 3520 Ser Pro Pro Ser Pro Gly Thr Thr Thr Pro Gly His Thr Arg Ala Thr 3525 3530 3535 Ser Arg Thr Thr Ala Thr Ala Thr Pro Ser Lys Thr Arg Thr Ser Thr 3540 3545 3550 Leu Leu Pro Ser Ser Pro Thr Ser Ala Pro Ile Thr Thr Val Val Thr 3555 3560 3565 Met Gly Cys Glu Pro Gln Cys Ala Trp Ser Glu Trp Leu Asp Tyr Ser 3570 3575 3580 Tyr Pro Met Pro Gly Pro Ser Gly Gly Asp Phe Asp Thr Tyr Ser Asn 3585 3590 3595 3600 Ile Arg Ala Ala Gly Gly Ala Val Cys Glu Gln Pro Leu Gly Leu Glu 3605 3610 3615 Cys Arg Ala Gln Ala Gln Pro Gly Val Pro Leu Gly Glu Leu Gly Gln 3620 3625 3630 Val Val Glu Cys Ser Leu Asp Phe Gly Leu Val Cys Arg Asn Arg Glu 3635 3640 3645 Gln Val Gly Lys Phe Lys Met Cys Phe Asn Tyr Glu Ile Arg Val Phe 3650 3655 3660 Cys Cys Asn Tyr Gly His Cys Pro Ser Thr Pro Ala Thr Ser Ser Thr 3665 3670 3675 3680 Ala Met Pro Ser Ser Thr Pro Gly Thr Thr Trp Ile Leu Thr Glu Leu 3685 3690 3695 Thr Thr Thr Ala Thr Thr Thr Ala Ser Thr Gly Ser Thr Ala Thr Pro 3700 3705 3710 Ser Ser Thr Pro Gly Thr Ala Pro Pro Pro Lys Val Leu Thr Ser Pro 3715 3720 3725 Ala Thr Thr Pro Thr Ala Thr Ser Ser Lys Ala Thr Ser Ser Ser Ser 3730 3735 3740 Pro Arg Thr Ala Thr Thr Leu Pro Val Leu Thr Ser Thr Ala Thr Lys 3745 3750 3755 3760 Ser Thr Ala Thr Ser Val Thr Pro Ile Pro Ser Ser Thr Leu Gly Thr 3765 3770 3775 Thr Gly Thr Leu Pro Glu Gln Thr Thr Thr Pro Val Ala Thr Met Ser 3780 3785 3790 Thr Ile His Pro Ser Ser Thr Pro Glu Thr Thr His Thr Ser Thr Val 3795 3800 3805 Leu Thr Thr Lys Ala Thr Thr Thr Arg Ala Thr Ser Ser Thr Ser Thr 3810 3815 3820 Pro Ser Ser Thr Pro Gly Thr Thr Trp Ile Leu Thr Glu Leu Thr Thr 3825 3830 3835 3840 Ala Ala Thr Thr Thr Ala Ala Thr Gly Pro Thr Ala Thr Pro Ser Ser 3845 3850 3855 Thr Pro Gly Thr Thr Trp Ile Leu Thr Glu Leu Thr Thr Thr Ala Thr 3860 3865 3870 Thr Thr Ala Ser Thr Gly Ser Thr Ala Thr Pro Ser Ser Thr Pro Gly 3875 3880 3885 Thr Thr Trp Ile Leu Thr Glu Pro Ser Thr Thr Ala Thr Val Thr Val 3890 3895 3900 Pro Thr Gly Ser Thr Ala Thr Ala Ser Ser Thr Gln Ala Thr Ala Gly 3905 3910 3915 3920 Thr Pro His Val Ser Thr Thr Ala Thr Thr Pro Thr Val Thr Ser Ser 3925 3930 3935 Lys Ala Thr Pro Ser Ser Ser Pro Gly Thr Ala Thr Ala Leu Pro Ala 3940 3945 3950 Leu Arg Ser Thr Ala Thr Thr Pro Thr Ala Thr Ser Phe Thr Ala Ile 3955 3960 3965 Pro Ser Ser Ser Leu Gly Thr Thr Trp Thr Arg Leu Ser Gln Thr Thr 3970 3975 3980 Thr Pro Thr Ala Thr Met Ser Thr Ala Thr Pro Ser Ser Thr Pro Glu 3985 3990 3995 4000 Thr Val His Thr Ser Thr Val Leu Thr Ala Thr Ala Thr Thr Thr Gly 4005 4010 4015 Ala Thr Gly Ser Val Ala Thr Pro Ser Ser Thr Pro Gly Thr Ala His 4020 4025 4030 Thr Thr Lys Val Pro Thr Thr Thr Thr Thr Gly Phe Thr Ala Thr Pro 4035 4040 4045 Ser Ser Ser Pro Gly Thr Ala Leu Thr Pro Pro Val Trp Ile Ser Thr 4050 4055 4060 Thr Thr Thr Pro Thr Thr Thr Thr Pro Thr Thr Ser Gly Ser Thr Val 4065 4070 4075 4080 Thr Pro Ser Ser Ile Pro Gly Thr Thr His Thr Ala Arg Val Leu Thr 4085 4090 4095 Thr Thr Thr Thr Thr Val Ala Thr Gly Ser Met Ala Thr Pro Ser Ser 4100 4105 4110 Ser Thr Gln Thr Ser Gly Thr Pro Pro Ser Leu Thr Thr Thr Ala Thr 4115 4120 4125 Thr Ile Thr Ala Thr Gly Ser Thr Thr Asn Pro Ser Ser Thr Pro Gly 4130 4135 4140 Thr Thr Pro Ile Thr Pro Val Leu Thr Ser Thr Ala Thr Thr Pro Ala 4145 4150 4155 4160 Ala Thr Ser Ser Lys Ala Thr Ser Ser Ser Ser Pro Arg Thr Ala Thr 4165 4170 4175 Thr Leu Pro Val Leu Thr Ser Thr Ala Thr Lys Ser Thr Ala Thr Ser 4180 4185 4190 Phe Thr Pro Ile Pro Ser Ser Thr Leu Trp Thr Thr Trp Thr Val Pro 4195 4200 4205 Ala Gln Thr Thr Thr Pro Met Ser Thr Met Ser Thr Ile His Thr Ser 4210 4215 4220 Ser Thr Pro Glu Thr Thr His Thr Ser Thr Val Leu Thr Thr Thr Ala 4225 4230 4235 4240 Thr Met Thr Arg Ala Thr Asn Ser Thr Ala Thr Pro Ser Ser Thr Leu 4245 4250 4255 Gly Thr Thr Arg Ile Leu Thr Glu Leu Thr Thr Thr Ala Thr Thr Thr 4260 4265 4270 Ala Ala Thr Gly Ser Thr Ala Thr Leu Ser Ser Thr Pro Gly Thr Thr 4275 4280 4285 Trp Ile Leu Thr Glu Pro Ser Thr Ile Ala Thr Val Met Val Pro Thr 4290 4295 4300 Gly Ser Thr Ala Thr Ala Ser Ser Thr Leu Gly Thr Ala His Thr Pro 4305 4310 4315 4320 Lys Val Val Thr Thr Met Ala Thr Met Pro Thr Ala Thr Ala Ser Thr 4325 4330 4335 Val Pro Ser Ser Ser Thr Val Gly Thr Thr Arg Thr Pro Ala Val Leu 4340 4345 4350 Pro Ser Ser Leu Pro Thr Phe Ser Val Ser Thr Val Ser Ser Ser Val 4355 4360 4365 Leu Thr Thr Leu Arg Pro Thr Gly Phe Pro Ser Ser His Phe Ser Thr 4370 4375 4380 Pro Cys Phe Cys Arg Ala Phe Gly Gln Phe Phe Ser Pro Gly Glu Val 4385 4390 4395 4400 Ile Tyr Asn Lys Thr Asp Arg Ala Gly Cys His Phe Tyr Ala Val Cys 4405 4410 4415 Asn Gln His Cys Asp Ile Asp Arg Phe Gln Gly Ala Cys Pro Thr Ser 4420 4425 4430 Pro Pro Pro Val Ser Ser Ala Pro Leu Ser Ser Pro Ser Pro Ala Pro 4435 4440 4445 Gly Cys Asp Asn Ala Ile Pro Leu Arg Gln Val Asn Glu Thr Trp Thr 4450 4455 4460 Leu Glu Asn Cys Thr Val Ala Arg Cys Val Gly Asp Asn Arg Val Val 4465 4470 4475 4480 Leu Leu Asp Pro Lys Pro Val Ala Asn Val Thr Cys Val Asn Lys His 4485 4490 4495 Leu Pro Ile Lys Val Ser Asp Pro Ser Gln Pro Cys Asp Phe His Tyr 4500 4505 4510 Glu Cys Glu Cys Ile Cys Ser Met Trp Gly Gly Ser His Tyr Ser Thr 4515 4520 4525 Phe Asp Gly Thr Ser Tyr Thr Phe Arg Gly Asn Cys Thr Tyr Val Leu 4530 4535 4540 Met Arg Glu Ile His Ala Arg Phe Gly Asn Leu Ser Leu Tyr Leu Asp 4545 4550 4555 4560 Asn His Tyr Cys Thr Ala Ser Ala Thr Ala Ala Ala Ala Arg Cys Pro 4565 4570 4575 Arg Ala Leu Ser Ile His Tyr Lys Ser Met Asp Ile Val Leu Thr Val 4580 4585 4590 Thr Met Val His Gly Lys Glu Glu Gly Leu Ile Leu Phe Asp Gln Ile 4595 4600 4605 Pro Val Ser Ser Gly Phe Ser Lys Asn Gly Val Leu Val Ser Val Leu 4610 4615 4620 Gly Thr Thr Thr Met Arg Val Asp Ile Pro Ala Leu Gly Val Ser Val 4625 4630 4635 4640 Thr Phe Asn Gly Gln Val Phe Gln Ala Arg Leu Pro Tyr Ser Leu Phe 4645 4650 4655 His Asn Asn Thr Glu Gly Gln Cys Gly Thr Cys Thr Asn Asn Gln Arg 4660 4665 4670 Asp Asp Cys Leu Gln Arg Asp Gly Thr Thr Ala Ala Ser Cys Lys Asp 4675 4680 4685 Met Ala Lys Thr Trp Leu Val Pro Asp Ser Arg Lys Asp Gly Cys Trp 4690 4695 4700 Ala Pro Thr Gly Thr Pro Pro Thr Ala Ser Pro Ala Ala Pro Val Ser 4705 4710 4715 4720 Ser Thr Pro Thr Pro Thr Pro Cys Pro Pro Gln Pro Leu Cys Asp Leu 4725 4730 4735 Met Leu Ser Gln Val Phe Ala Glu Cys His Asn Leu Val Pro Pro Gly 4740 4745 4750 Pro Phe Phe Asn Ala Cys Ile Ser Asp His Cys Arg Gly Arg Leu Glu 4755 4760 4765 Val Pro Cys Gln Ser Leu Glu Ala Tyr Ala Glu Leu Cys Arg Ala Arg 4770 4775 4780 Gly Val Cys Ser Asp Trp Arg Gly Ala Thr Gly Gly Leu Cys Asp Leu 4785 4790 4795 4800 Thr Cys Pro Pro Thr Lys Val Tyr Lys Pro Cys Gly Pro Ile Gln Pro 4805 4810 4815 Ala Thr Cys Asn Ser Arg Asn Gln Ser Pro Gln Leu Glu Gly Met Ala 4820 4825 4830 Glu Gly Cys Phe Cys Pro Glu Asp Gln Ile Leu Phe Asn Ala His Met 4835 4840 4845 Gly Ile Cys Val Gln Ala Cys Pro Cys Val Gly Pro Asp Gly Phe Pro 4850 4855 4860 Lys Phe Pro Gly Glu Arg Trp Val Ser Asn Cys Gln Ser Cys Val Cys 4865 4870 4875 4880 Asp Glu Gly Ser Val Ser Val Gln Cys Lys Pro Leu Pro Cys Asp Ala 4885 4890 4895 Gln Gly Gln Pro Pro Pro Cys Asn Arg Pro Gly Phe Val Thr Val Thr 4900 4905 4910 Arg Pro Arg Ala Glu Asn Pro Cys Cys Pro Glu Thr Val Cys Val Cys 4915 4920 4925 Asn Thr Thr Thr Cys Pro Gln Ser Leu Pro Val Cys Pro Pro Gly Gln 4930 4935 4940 Glu Ser Ile Cys Thr Gln Glu Glu Gly Asp Cys Cys Pro Thr Phe Arg 4945 4950 4955 4960 Cys Arg Pro Gln Leu Cys Ser Tyr Asn Gly Thr Phe Tyr Gly Val Gly 4965 4970 4975 Ala Thr Phe Pro Gly Ala Leu Pro Cys His Met Cys Thr Cys Leu Ser 4980 4985 4990 Gly Asp Thr Gln Asp Pro Thr Val Gln Cys Gln Glu Asp Ala Cys Asn 4995 5000 5005 Asn Thr Thr Cys Pro Gln Gly Phe Glu Tyr Lys Arg Val Ala Gly Gln 5010 5015 5020 Cys Cys Gly Glu Cys Val Gln Thr Ala Cys Leu Thr Pro Asp Gly Gln 5025 5030 5035 5040 Pro Val Gln Leu Asn Glu Thr Trp Val Asn Ser His Val Asp Asn Cys 5045 5050 5055 Thr Val Tyr Leu Cys Glu Ala Glu Gly Gly Val His Leu Leu Thr Pro 5060 5065 5070 Gln Pro Ala Ser Cys Pro Asp Val Ser Ser Cys Arg Gly Ser Leu Arg 5075 5080 5085 Lys Thr Gly Cys Cys Tyr Ser Cys Glu Glu Asp Ser Cys Gln Val Arg 5090 5095 5100 Ile Asn Thr Thr Ile Leu Trp His Gln Gly Cys Glu Thr Glu Val Asn 5105 5110 5115 5120 Ile Thr Phe Cys Glu Gly Ser Cys Pro Gly Ala Ser Lys Tyr Ser Ala 5125 5130 5135 Glu Ala Gln Ala Met Gln His Gln Cys Thr Cys Cys Gln Glu Arg Arg 5140 5145 5150 Val His Glu Glu Thr Val Pro Leu His Cys Pro Asn Gly Ser Ala Ile 5155 5160 5165 Leu His Thr Tyr Thr His Val Asp Glu Cys Gly Cys Thr Pro Phe Cys 5170 5175 5180 Val Pro Ala Pro Met Ala Pro Pro His Thr Arg Gly Phe Pro Ala Gln 5185 5190 5195 5200 Glu Ala Thr Ala Val 5205 <210> 55 <211> 949 <212> PRT <213> Homo sapiens <400> 55 Met Ile Leu Ser Leu Leu Phe Ser Leu Gly Gly Pro Leu Gly Trp Gly 1 5 10 15 Leu Leu Gly Ala Trp Ala Gln Ala Ser Ser Thr Ser Leu Ser Asp Leu 20 25 30 Gln Ser Ser Arg Thr Pro Gly Val Trp Lys Ala Glu Ala Glu Asp Thr 35 40 45 Ser Lys Asp Pro Val Gly Arg Asn Trp Cys Pro Tyr Pro Met Ser Lys 50 55 60 Leu Val Thr Leu Leu Ala Leu Cys Lys Thr Glu Lys Phe Leu Ile His 65 70 75 80 Ser Gln Gln Pro Cys Pro Gln Gly Ala Pro Asp Cys Gln Lys Val Lys 85 90 95 Val Met Tyr Arg Met Ala His Lys Pro Val Tyr Gln Val Lys Gln Lys 100 105 110 Val Leu Thr Ser Leu Ala Trp Arg Cys Cys Pro Gly Tyr Thr Gly Pro 115 120 125 Asn Cys Glu His His Asp Ser Met Ala Ile Pro Glu Pro Ala Asp Pro 130 135 140 Gly Asp Ser His Gln Glu Pro Gln Asp Gly Pro Val Ser Phe Lys Pro 145 150 155 160 Gly His Leu Ala Ala Val Ile Asn Glu Val Glu Val Gln Gln Glu Gln 165 170 175 Gln Glu His Leu Leu Gly Asp Leu Gln Asn Asp Val His Arg Val Ala 180 185 190 Asp Ser Leu Pro Gly Leu Trp Lys Ala Leu Pro Gly Asn Leu Thr Ala 195 200 205 Ala Val Met Glu Ala Asn Gln Thr Gly His Glu Phe Pro Asp Arg Ser 210 215 220 Leu Glu Gln Val Leu Leu Pro His Val Asp Thr Phe Leu Gln Val His 225 230 235 240 Phe Ser Pro Ile Trp Arg Ser Phe Asn Gln Ser Leu His Ser Leu Thr 245 250 255 Gln Ala Ile Arg Asn Leu Ser Leu Asp Val Glu Ala Asn Arg Gln Ala 260 265 270 Ile Ser Arg Val Gln Asp Ser Ala Val Ala Arg Ala Asp Phe Gln Glu 275 280 285 Leu Gly Ala Lys Phe Glu Ala Lys Val Gln Glu Asn Thr Gln Arg Val 290 295 300 Gly Gln Leu Arg Gln Asp Val Glu Asp Arg Leu His Ala Gln His Phe 305 310 315 320 Thr Leu His Arg Ser Ile Ser Glu Leu Gln Ala Asp Val Asp Thr Lys 325 330 335 Leu Lys Arg Leu His Lys Ala Gln Glu Ala Pro Gly Thr Asn Gly Ser 340 345 350 Leu Val Leu Ala Thr Pro Gly Ala Gly Ala Arg Pro Glu Pro Asp Ser 355 360 365 Leu Gln Ala Arg Leu Gly Gln Leu Gln Arg Asn Leu Ser Glu Leu His 370 375 380 Met Thr Thr Ala Arg Arg Glu Glu Glu Leu Gln Tyr Thr Leu Glu Asp 385 390 395 400 Met Arg Ala Thr Leu Thr Arg His Val Asp Glu Ile Lys Glu Leu Tyr 405 410 415 Ser Glu Ser Asp Glu Thr Phe Asp Gln Ile Ser Lys Val Glu Arg Gln 420 425 430 Val Glu Glu Leu Gln Val Asn His Thr Ala Leu Arg Glu Leu Arg Val 435 440 445 Ile Leu Met Glu Lys Ser Leu Ile Met Glu Glu Asn Lys Glu Glu Val 450 455 460 Glu Arg Gln Leu Leu Glu Leu Asn Leu Thr Leu Gln His Leu Gln Gly 465 470 475 480 Gly His Ala Asp Leu Ile Lys Tyr Val Lys Asp Cys Asn Cys Gln Lys 485 490 495 Leu Tyr Leu Asp Leu Asp Val Ile Arg Glu Gly Gln Arg Asp Ala Thr 500 505 510 Arg Ala Leu Glu Glu Thr Gln Val Ser Leu Asp Glu Arg Arg Gln Leu 515 520 525 Asp Gly Ser Ser Leu Gln Ala Leu Gln Asn Ala Val Asp Ala Val Ser 530 535 540 Leu Ala Val Asp Ala His Lys Ala Glu Gly Glu Arg Ala Arg Ala Ala 545 550 555 560 Thr Ser Arg Leu Arg Ser Gln Val Gln Ala Leu Asp Asp Glu Val Gly 565 570 575 Ala Leu Lys Ala Ala Ala Ala Glu Ala Arg His Glu Val Arg Gln Leu 580 585 590 His Ser Ala Phe Ala Ala Leu Leu Glu Asp Ala Leu Arg His Glu Ala 595 600 605 Val Leu Ala Ala Leu Phe Gly Glu Glu Val Leu Glu Glu Met Ser Glu 610 615 620 Gln Thr Pro Gly Pro Leu Pro Leu Ser Tyr Glu Gln Ile Arg Val Ala 625 630 635 640 Leu Gln Asp Ala Ala Ser Gly Leu Gln Glu Gln Ala Leu Gly Trp Asp 645 650 655 Glu Leu Ala Ala Arg Val Thr Ala Leu Glu Gln Ala Ser Glu Pro Pro 660 665 670 Arg Pro Ala Glu His Leu Glu Pro Ser His Asp Ala Gly Arg Glu Glu 675 680 685 Ala Ala Thr Thr Ala Leu Ala Gly Leu Ala Arg Glu Leu Gln Ser Leu 690 695 700 Ser Asn Asp Val Lys Asn Val Gly Arg Cys Cys Glu Ala Glu Ala Gly 705 710 715 720 Ala Gly Ala Ala Ser Leu Asn Ala Ser Leu Asp Gly Leu His Asn Ala 725 730 735 Leu Phe Ala Thr Gln Arg Ser Leu Glu Gln His Gln Arg Leu Phe His 740 745 750 Ser Leu Phe Gly Asn Phe Gln Gly Leu Met Glu Ala Asn Val Ser Leu 755 760 765 Asp Leu Gly Lys Leu Gln Thr Met Leu Ser Arg Lys Gly Lys Lys Gln 770 775 780 Gln Lys Asp Leu Glu Ala Pro Arg Lys Arg Asp Lys Lys Glu Ala Glu 785 790 795 800 Pro Leu Val Asp Ile Arg Val Thr Gly Pro Val Pro Gly Ala Leu Gly 805 810 815 Ala Ala Leu Trp Glu Ala Gly Ser Pro Val Ala Phe Tyr Ala Ser Phe 820 825 830 Ser Glu Gly Thr Ala Ala Leu Gln Thr Val Lys Phe Asn Thr Thr Tyr 835 840 845 Ile Asn Ile Gly Ser Ser Tyr Phe Pro Glu His Gly Tyr Phe Arg Ala 850 855 860 Pro Glu Arg Gly Val Tyr Leu Phe Ala Val Ser Val Glu Phe Gly Pro 865 870 875 880 Gly Pro Gly Thr Gly Gln Leu Val Phe Gly Gly His His Arg Thr Pro 885 890 895 Val Cys Thr Thr Gly Gln Gly Ser Gly Ser Thr Ala Thr Val Phe Ala 900 905 910 Met Ala Glu Leu Gln Lys Gly Glu Arg Val Trp Phe Glu Leu Thr Gln 915 920 925 Gly Ser Ile Thr Lys Arg Ser Leu Ser Gly Thr Ala Phe Gly Gly Phe 930 935 940 Leu Met Phe Lys Thr 945 <210> 56 <211> 504 <212> PRT <213> Homo sapiens <400> 56 Met Arg Phe Phe Cys Ala Arg Cys Cys Ser Phe Gly Pro Glu Met Pro 1 5 10 15 Ala Val Gln Leu Leu Leu Leu Ala Cys Leu Val Trp Asp Val Gly Ala 20 25 30 Arg Thr Ala Gln Leu Arg Lys Ala Asn Asp Gln Ser Gly Arg Cys Gln 35 40 45 Tyr Thr Phe Ser Val Ala Ser Pro Asn Glu Ser Ser Cys Pro Glu Gln 50 55 60 Ser Gln Ala Met Ser Val Ile His Asn Leu Gln Arg Asp Ser Ser Thr 65 70 75 80 Gln Arg Leu Asp Leu Glu Ala Thr Lys Ala Arg Leu Ser Ser Leu Glu 85 90 95 Ser Leu Leu His Gln Leu Thr Leu Asp Gln Ala Ala Arg Pro Gln Glu 100 105 110 Thr Gln Glu Gly Leu Gln Arg Glu Leu Gly Thr Leu Arg Arg Glu Arg 115 120 125 Asp Gln Leu Glu Thr Gln Thr Arg Glu Leu Glu Thr Ala Tyr Ser Asn 130 135 140 Leu Leu Arg Asp Lys Ser Val Leu Glu Glu Glu Lys Lys Arg Leu Arg 145 150 155 160 Gln Glu Asn Glu Asn Leu Ala Arg Arg Leu Glu Ser Ser Ser Gln Glu 165 170 175 Val Ala Arg Leu Arg Arg Gly Gln Cys Pro Gln Thr Arg Asp Thr Ala 180 185 190 Arg Ala Val Pro Pro Gly Ser Arg Glu Val Ser Thr Trp Asn Leu Asp 195 200 205 Thr Leu Ala Phe Gln Glu Leu Lys Ser Glu Leu Thr Glu Val Pro Ala 210 215 220 Ser Arg Ile Leu Lys Glu Ser Pro Ser Gly Tyr Leu Arg Ser Gly Glu 225 230 235 240 Gly Asp Thr Gly Cys Gly Glu Leu Val Trp Val Gly Glu Pro Leu Thr 245 250 255 Leu Arg Thr Ala Glu Thr Ile Thr Gly Lys Tyr Gly Val Trp Met Arg 260 265 270 Asp Pro Lys Pro Thr Tyr Pro Tyr Thr Gln Glu Thr Thr Trp Arg Ile 275 280 285 Asp Thr Val Gly Thr Asp Val Arg Gln Val Phe Glu Tyr Asp Leu Ile 290 295 300 Ser Gln Phe Met Gln Gly Tyr Pro Ser Lys Val His Ile Leu Pro Arg 305 310 315 320 Pro Leu Glu Ser Thr Gly Ala Val Val Tyr Ser Gly Ser Leu Tyr Phe 325 330 335 Gln Gly Ala Glu Ser Arg Thr Val Ile Arg Tyr Glu Leu Asn Thr Glu 340 345 350 Thr Val Lys Ala Glu Lys Glu Ile Pro Gly Ala Gly Tyr His Gly Gln 355 360 365 Phe Pro Tyr Ser Trp Gly Gly Tyr Thr Asp Ile Asp Leu Ala Val Asp 370 375 380 Glu Ala Gly Leu Trp Val Ile Tyr Ser Thr Asp Glu Ala Lys Gly Ala 385 390 395 400 Ile Val Leu Ser Lys Leu Asn Pro Glu Asn Leu Glu Leu Glu Gln Thr 405 410 415 Trp Glu Thr Asn Ile Arg Lys Gln Ser Val Ala Asn Ala Phe Ile Ile 420 425 430 Cys Gly Thr Leu Tyr Thr Val Ser Ser Tyr Thr Ser Ala Asp Ala Thr 435 440 445 Val Asn Phe Ala Tyr Asp Thr Gly Thr Gly Ile Ser Lys Thr Leu Thr 450 455 460 Ile Pro Phe Lys Asn Arg Tyr Lys Tyr Ser Ser Met Ile Asp Tyr Asn 465 470 475 480 Pro Leu Glu Lys Lys Leu Phe Ala Trp Asp Asn Leu Asn Met Val Thr 485 490 495 Tyr Asp Ile Lys Leu Ser Lys Met 500 <210> 57 <211> 153 <212> PRT <213> Homo sapiens <400> 57 Gly Leu Ser Asp Gly Glu Trp Gln Leu Val Leu Asn Val Trp Gly Lys 1 5 10 15 Val Glu Ala Asp Ile Pro Gly His Gly Gln Glu Val Leu Ile Arg Leu 20 25 30 Phe Lys Gly His Pro Glu Thr Leu Glu Lys Phe Asp Lys Phe Lys His 35 40 45 Leu Lys Ser Glu Asp Glu Met Lys Ala Ser Glu Asp Leu Lys Lys His 50 55 60 Gly Ala Thr Val Leu Thr Ala Leu Gly Gly Ile Leu Lys Lys Lys Gly 65 70 75 80 His His Glu Ala Glu Ile Lys Pro Leu Ala Gln Ser His Ala Thr Lys 85 90 95 His Lys Ile Pro Val Lys Tyr Leu Glu Phe Ile Ser Glu Cys Ile Ile 100 105 110 Gln Val Leu Gln Ser Lys His Pro Gly Asp Phe Gly Ala Asp Ala Gln 115 120 125 Gly Ala Met Asn Lys Ala Leu Glu Leu Phe Arg Lys Asp Met Ala Ser 130 135 140 Asn Tyr Lys Glu Leu Gly Phe Gln Gly 145 150 <210> 58 <211> 1392 <212> PRT <213> Homo sapiens <400> 58 Met Ser Ser Thr Leu His Ser Val Phe Phe Thr Leu Lys Val Ser Ile 1 5 10 15 Leu Leu Gly Ser Leu Leu Gly Leu Cys Leu Gly Leu Glu Phe Met Gly 20 25 30 Leu Pro Asn Gln Trp Ala Arg Tyr Leu Arg Trp Asp Ala Ser Thr Arg 35 40 45 Ser Asp Leu Ser Phe Gln Phe Lys Thr Asn Val Ser Thr Gly Leu Leu 50 55 60 Leu Tyr Leu Asp Asp Gly Gly Val Cys Asp Phe Leu Cys Leu Ser Leu 65 70 75 80 Val Asp Gly Arg Val Gln Leu Arg Phe Ser Met Asp Cys Ala Glu Thr 85 90 95 Ala Val Leu Ser Asn Lys Gln Val Asn Asp Ser Ser Trp His Phe Leu 100 105 110 Met Val Ser Arg Asp Arg Leu Arg Thr Val Leu Met Leu Asp Gly Glu 115 120 125 Gly Gln Ser Gly Glu Leu Gln Pro Gln Arg Pro Tyr Met Asp Val Val 130 135 140 Ser Asp Leu Phe Leu Gly Gly Val Pro Thr Asp Ile Arg Pro Ser Ala 145 150 155 160 Leu Thr Leu Asp Gly Val Gln Ala Met Pro Gly Phe Lys Gly Leu Ile 165 170 175 Leu Asp Leu Lys Tyr Gly Asn Ser Glu Pro Arg Leu Leu Gly Ser Arg 180 185 190 Gly Val Gln Met Asp Ala Glu Gly Pro Cys Gly Glu Arg Pro Cys Glu 195 200 205 Asn Gly Gly Ile Cys Phe Leu Leu Asp Gly His Pro Thr Cys Asp Cys 210 215 220 Ser Thr Thr Gly Tyr Gly Gly Lys Leu Cys Ser Glu Gly Leu Ser His 225 230 235 240 Leu Met Met Ser Glu Gln Gly Arg Ser Lys Ala Arg Glu Glu Asn Val 245 250 255 Ala Thr Phe Arg Gly Ser Glu Tyr Leu Cys Tyr Asp Leu Ser Gln Asn 260 265 270 Pro Ile Gln Ser Ser Ser Asp Glu Ile Thr Leu Ser Phe Lys Thr Trp 275 280 285 Gln Arg Asn Gly Leu Ile Leu His Thr Gly Lys Ser Ala Asp Tyr Val 290 295 300 Asn Leu Ala Leu Lys Asp Gly Ala Val Ser Leu Val Ile Asn Leu Gly 305 310 315 320 Ser Gly Ala Phe Glu Ala Ile Val Glu Pro Val Asn Gly Lys Phe Asn 325 330 335 Asp Asn Ala Trp His Asp Val Lys Val Thr Arg Asn Leu Arg Gln Val 340 345 350 Thr Ile Ser Val Asp Gly Ile Leu Thr Thr Thr Gly Tyr Thr Gln Glu 355 360 365 Asp Tyr Thr Met Leu Gly Ser Asp Asp Phe Phe Tyr Val Gly Gly Ser 370 375 380 Pro Ser Thr Ala Asp Leu Pro Gly Ser Pro Val Ser Asn Asn Phe Met 385 390 395 400 Gly Cys Leu Lys Glu Val Val Tyr Lys Asn Asn Asp Ile Arg Leu Glu 405 410 415 Leu Ser Arg Leu Ala Arg Ile Ala Asp Thr Lys Met Lys Ile Tyr Gly 420 425 430 Glu Val Val Phe Lys Cys Glu Asn Val Ala Thr Leu Asp Pro Ile Asn 435 440 445 Phe Glu Thr Pro Glu Ala Tyr Ile Ser Leu Pro Lys Trp Asn Thr Lys 450 455 460 Arg Met Gly Ser Ile Ser Phe Asp Phe Arg Thr Thr Glu Pro Asn Gly 465 470 475 480 Leu Ile Leu Phe Thr His Gly Lys Pro Gln Glu Arg Lys Asp Ala Arg 485 490 495 Ser Gln Lys Asn Thr Lys Val Asp Phe Phe Ala Val Glu Leu Leu Asp 500 505 510 Gly Asn Leu Tyr Leu Leu Leu Asp Met Gly Ser Gly Thr Ile Lys Val 515 520 525 Lys Ala Thr Gln Lys Lys Ala Asn Asp Gly Glu Trp Tyr His Val Asp 530 535 540 Ile Gln Arg Asp Gly Arg Ser Gly Thr Ile Ser Val Asn Ser Arg Arg 545 550 555 560 Thr Pro Phe Thr Ala Ser Gly Glu Ser Glu Ile Leu Asp Leu Glu Gly 565 570 575 Asp Met Tyr Leu Gly Gly Leu Pro Glu Asn Arg Ala Gly Leu Ile Leu 580 585 590 Pro Thr Glu Leu Trp Thr Ala Met Leu Asn Tyr Gly Tyr Val Gly Cys 595 600 605 Ile Arg Asp Leu Phe Ile Asp Gly Arg Ser Lys Asn Ile Arg Gln Leu 610 615 620 Ala Glu Met Gln Asn Ala Ala Gly Val Lys Ser Ser Cys Ser Arg Met 625 630 635 640 Ser Ala Lys Gln Cys Asp Ser Tyr Pro Cys Lys Asn Asn Ala Val Cys 645 650 655 Lys Asp Gly Trp Asn Arg Phe Ile Cys Asp Cys Thr Gly Thr Gly Tyr 660 665 670 Trp Gly Arg Thr Cys Glu Arg Glu Ala Ser Ile Leu Ser Tyr Asp Gly 675 680 685 Ser Met Tyr Met Lys Ile Ile Met Pro Met Val Met His Thr Glu Ala 690 695 700 Glu Asp Val Ser Phe Arg Phe Met Ser Gln Arg Ala Tyr Gly Leu Leu 705 710 715 720 Val Ala Thr Thr Ser Arg Asp Ser Ala Asp Thr Leu Arg Leu Glu Leu 725 730 735 Asp Gly Gly Arg Val Lys Leu Met Val Asn Leu Gly Lys Gly Pro Glu 740 745 750 Thr Leu Tyr Ala Gly Gln Lys Leu Asn Asp Asn Glu Trp His Thr Val 755 760 765 Arg Val Val Arg Arg Gly Lys Ser Leu Lys Leu Thr Val Asp Asp Asp 770 775 780 Val Ala Glu Gly Thr Met Val Gly Asp His Thr Arg Leu Glu Phe His 785 790 795 800 Asn Ile Glu Thr Gly Ile Met Thr Glu Lys Arg Tyr Ile Ser Val Val 805 810 815 Pro Ser Ser Phe Ile Gly His Leu Gln Ser Leu Met Phe Asn Gly Leu 820 825 830 Leu Tyr Ile Asp Leu Cys Lys Asn Gly Asp Ile Asp Tyr Cys Glu Leu 835 840 845 Lys Ala Arg Phe Gly Leu Arg Asn Ile Ile Ala Asp Pro Val Thr Phe 850 855 860 Lys Thr Lys Ser Ser Tyr Leu Ser Leu Ala Thr Leu Gln Ala Tyr Thr 865 870 875 880 Ser Met His Leu Phe Phe Gln Phe Lys Thr Thr Ser Pro Asp Gly Phe 885 890 895 Ile Leu Phe Asn Ser Gly Asp Gly Asn Asp Phe Ile Ala Val Glu Leu 900 905 910 Val Lys Gly Tyr Ile His Tyr Val Phe Asp Leu Gly Asn Gly Pro Asn 915 920 925 Val Ile Lys Gly Asn Ser Asp Arg Pro Leu Asn Asp Asn Gln Trp His 930 935 940 Asn Val Val Ile Thr Arg Asp Asn Ser Asn Thr His Ser Leu Lys Val 945 950 955 960 Asp Thr Lys Val Val Thr Gln Val Ile Asn Gly Ala Lys Asn Leu Asp 965 970 975 Leu Lys Gly Asp Leu Tyr Met Ala Gly Leu Ala Gln Gly Met Tyr Ser 980 985 990 Asn Leu Pro Lys Leu Val Ala Ser Arg Asp Gly Phe Gln Gly Cys Leu 995 1000 1005 Ala Ser Val Asp Leu Asn Gly Arg Leu Pro Asp Leu Ile Asn Asp Ala 1010 1015 1020 Leu His Arg Ser Gly Gln Ile Glu Arg Gly Cys Glu Gly Pro Ser Thr 1025 1030 1035 1040 Thr Cys Gln Glu Asp Ser Cys Ala Asn Gln Gly Val Cys Met Gln Gln 1045 1050 1055 Trp Glu Gly Phe Thr Cys Asp Cys Ser Met Thr Ser Tyr Ser Gly Asn 1060 1065 1070 Gln Cys Asn Asp Pro Gly Ala Thr Tyr Ile Phe Gly Lys Ser Gly Gly 1075 1080 1085 Leu Ile Leu Tyr Thr Trp Pro Ala Asn Asp Arg Pro Ser Thr Arg Ser 1090 1095 1100 Asp Arg Leu Ala Val Gly Phe Ser Thr Thr Val Lys Asp Gly Ile Leu 1105 1110 1115 1120 Val Arg Ile Asp Ser Ala Pro Gly Leu Gly Asp Phe Leu Gln Leu His 1125 1130 1135 Ile Glu Gln Gly Lys Ile Gly Val Val Phe Asn Ile Gly Thr Val Asp 1140 1145 1150 Ile Ser Ile Lys Glu Glu Arg Thr Pro Val Asn Asp Gly Lys Tyr His 1155 1160 1165 Val Val Arg Phe Thr Arg Asn Gly Gly Asn Ala Thr Leu Gln Val Asp 1170 1175 1180 Asn Trp Pro Val Asn Glu His Tyr Pro Thr Gly Asn Thr Asp Asn Glu 1185 1190 1195 1200 Arg Phe Gln Met Val Lys Gln Lys Ile Pro Phe Lys Tyr Asn Arg Pro 1205 1210 1215 Val Glu Glu Trp Leu Gln Glu Lys Gly Arg Gln Leu Thr Ile Phe Asn 1220 1225 1230 Thr Gln Ala Gln Ile Ala Ile Gly Gly Lys Asp Lys Gly Arg Leu Phe 1235 1240 1245 Gln Gly Gln Leu Ser Gly Leu Tyr Tyr Asp Gly Leu Lys Val Leu Asn 1250 1255 1260 Met Ala Ala Glu Asn Asn Pro Asn Ile Lys Ile Asn Gly Ser Val Arg 1265 1270 1275 1280 Leu Val Gly Glu Val Pro Ser Ile Leu Gly Thr Thr Gln Thr Thr Ser 1285 1290 1295 Met Pro Pro Glu Met Ser Thr Thr Val Met Glu Thr Thr Thr Thr Met 1300 1305 1310 Ala Thr Thr Thr Thr Arg Lys Asn Arg Ser Thr Ala Ser Ile Gln Pro 1315 1320 1325 Thr Ser Asp Asp Leu Val Ser Ser Ala Glu Cys Ser Ser Asp Asp Glu 1330 1335 1340 Asp Phe Val Glu Cys Glu Pro Ser Thr Gly Arg Ser Ala Arg Ser Ser 1345 1350 1355 1360 Asn Ala Ala Arg Ser Leu Arg Ala Ala Leu Thr Trp Thr Trp Arg Leu 1365 1370 1375 Thr Tyr Thr Phe Thr Pro Ile Ile Phe Ile Ser Cys Val Val His Ser 1380 1385 1390 <210> 59 <211> 1375 <212> PRT <213> Homo sapiens <400> 59 Met Glu Gly Asp Arg Val Ala Gly Arg Pro Val Leu Ser Ser Leu Pro 1 5 10 15 Val Leu Leu Leu Leu Gln Leu Leu Met Leu Arg Ala Ala Ala Leu His 20 25 30 Pro Asp Glu Leu Phe Pro His Gly Glu Ser Trp Gly Asp Gln Leu Leu 35 40 45 Gln Glu Gly Asp Asp Glu Ser Ser Ala Val Val Lys Leu Ala Asn Pro 50 55 60 Leu His Phe Tyr Glu Ala Arg Phe Ser Asn Leu Tyr Val Gly Thr Asn 65 70 75 80 Gly Ile Ile Ser Thr Gln Asp Phe Pro Arg Glu Thr Gln Tyr Val Asp 85 90 95 Tyr Asp Phe Pro Thr Asp Phe Pro Ala Ile Ala Pro Phe Leu Ala Asp 100 105 110 Ile Asp Thr Ser His Gly Arg Gly Arg Val Leu Tyr Arg Glu Asp Thr 115 120 125 Ser Pro Ala Val Leu Gly Leu Ala Ala Arg Tyr Val Arg Ala Gly Phe 130 135 140 Pro Arg Ser Ala Arg Phe Thr Pro Thr His Ala Phe Leu Ala Thr Trp 145 150 155 160 Glu Gln Val Gly Ala Tyr Glu Glu Val Lys Arg Gly Ala Leu Pro Ser 165 170 175 Gly Glu Leu Asn Thr Phe Gln Ala Val Leu Ala Ser Asp Gly Ser Asp 180 185 190 Ser Tyr Ala Leu Phe Leu Tyr Pro Ala Asn Gly Leu Gln Phe Leu Gly 195 200 205 Thr Arg Pro Lys Glu Ser Tyr Asn Val Gln Leu Gln Leu Pro Ala Arg 210 215 220 Val Gly Phe Cys Arg Gly Glu Ala Asp Asp Leu Lys Ser Glu Gly Pro 225 230 235 240 Tyr Phe Ser Leu Thr Ser Thr Glu Gln Ser Val Lys Asn Leu Tyr Gln 245 250 255 Leu Ser Asn Leu Gly Ile Pro Gly Val Trp Ala Phe His Ile Gly Ser 260 265 270 Thr Ser Pro Leu Asp Asn Val Arg Pro Ala Ala Val Gly Asp Leu Ser 275 280 285 Ala Ala His Ser Ser Val Pro Leu Gly Arg Ser Phe Ser His Ala Thr 290 295 300 Ala Leu Glu Ser Asp Tyr Asn Glu Asp Asn Leu Asp Tyr Tyr Asp Val 305 310 315 320 Asn Glu Glu Glu Ala Glu Tyr Leu Pro Gly Glu Pro Glu Glu Ala Leu 325 330 335 Asn Gly His Ser Ser Ile Asp Val Ser Phe Gln Ser Lys Val Asp Thr 340 345 350 Lys Pro Leu Glu Glu Ser Ser Thr Leu Asp Pro His Thr Lys Glu Gly 355 360 365 Thr Ser Leu Gly Glu Val Gly Gly Pro Asp Leu Lys Gly Gln Val Glu 370 375 380 Pro Trp Asp Glu Arg Glu Thr Arg Ser Pro Ala Pro Pro Glu Val Asp 385 390 395 400 Arg Asp Ser Leu Ala Pro Ser Trp Glu Thr Pro Pro Pro Tyr Pro Glu 405 410 415 Asn Gly Ser Ile Gln Pro Tyr Pro Asp Gly Gly Pro Val Pro Ser Glu 420 425 430 Met Asp Val Pro Pro Ala His Pro Glu Glu Glu Ile Val Leu Arg Ser 435 440 445 Tyr Pro Ala Ser Asp His Thr Thr Pro Leu Ser Arg Gly Thr Tyr Glu 450 455 460 Val Gly Leu Glu Asp Asn Ile Gly Ser Asn Thr Glu Val Phe Thr Tyr 465 470 475 480 Asn Ala Ala Asn Lys Glu Thr Cys Glu His Asn His Arg Gln Cys Ser 485 490 495 Arg His Ala Phe Cys Thr Asp Tyr Ala Thr Gly Phe Cys Cys His Cys 500 505 510 Gln Ser Lys Phe Tyr Gly Asn Gly Lys His Cys Leu Pro Glu Gly Ala 515 520 525 Pro His Arg Val Asn Gly Lys Val Ser Gly His Leu His Val Gly His 530 535 540 Thr Pro Val His Phe Thr Asp Val Asp Leu His Ala Tyr Ile Val Gly 545 550 555 560 Asn Asp Gly Arg Ala Tyr Thr Ala Ile Ser His Ile Pro Gln Pro Ala 565 570 575 Ala Gln Ala Leu Leu Pro Leu Thr Pro Ile Gly Gly Leu Phe Gly Trp 580 585 590 Leu Phe Ala Leu Glu Lys Pro Gly Ser Glu Asn Gly Phe Ser Leu Ala 595 600 605 Gly Ala Ala Phe Thr His Asp Met Glu Val Thr Phe Tyr Pro Gly Glu 610 615 620 Glu Thr Val Arg Ile Thr Gln Thr Ala Glu Gly Leu Asp Pro Glu Asn 625 630 635 640 Tyr Leu Ser Ile Lys Thr Asn Ile Gln Gly Gln Val Pro Tyr Val Pro 645 650 655 Ala Asn Phe Thr Ala His Ile Ser Pro Tyr Lys Glu Leu Tyr His Tyr 660 665 670 Ser Asp Ser Thr Val Thr Ser Thr Ser Ser Arg Asp Tyr Ser Leu Thr 675 680 685 Phe Gly Ala Ile Asn Gln Thr Trp Ser Tyr Arg Ile His Gln Asn Ile 690 695 700 Thr Tyr Gln Val Cys Arg His Ala Pro Arg His Pro Ser Phe Pro Thr 705 710 715 720 Thr Gln Gln Leu Asn Val Asp Arg Val Phe Ala Leu Tyr Asn Asp Glu 725 730 735 Glu Arg Val Leu Arg Phe Ala Val Thr Asn Gln Ile Gly Pro Val Lys 740 745 750 Glu Asp Ser Asp Pro Thr Pro Val Asn Pro Cys Tyr Asp Gly Ser His 755 760 765 Met Cys Asp Thr Thr Ala Arg Cys His Pro Gly Thr Gly Val Asp Tyr 770 775 780 Thr Cys Glu Cys Ala Ser Gly Tyr Gln Gly Asp Gly Arg Asn Cys Val 785 790 795 800 Asp Glu Asn Glu Cys Ala Thr Gly Phe His Arg Cys Gly Pro Asn Ser 805 810 815 Val Cys Ile Asn Leu Pro Gly Ser Tyr Arg Cys Glu Cys Arg Ser Gly 820 825 830 Tyr Glu Phe Ala Asp Asp Arg His Thr Cys Ile Leu Ile Thr Pro Pro 835 840 845 Ala Asn Pro Cys Glu Asp Gly Ser His Thr Cys Ala Pro Ala Gly Gln 850 855 860 Ala Arg Cys Val His His Gly Gly Ser Thr Phe Ser Cys Ala Cys Leu 865 870 875 880 Pro Gly Tyr Ala Gly Asp Gly His Gln Cys Thr Asp Val Asp Glu Cys 885 890 895 Ser Glu Asn Arg Cys His Pro Ala Ala Thr Cys Tyr Asn Thr Pro Gly 900 905 910 Ser Phe Ser Cys Arg Cys Gln Pro Gly Tyr Tyr Gly Asp Gly Phe Gln 915 920 925 Cys Ile Pro Asp Ser Thr Ser Ser Leu Thr Pro Cys Glu Gln Gln Gln 930 935 940 Arg His Ala Gln Ala Gln Tyr Ala Tyr Pro Gly Ala Arg Phe His Ile 945 950 955 960 Pro Gln Cys Asp Glu Gln Gly Asn Phe Leu Pro Leu Gln Cys His Gly 965 970 975 Ser Thr Gly Phe Cys Trp Cys Val Asp Pro Asp Gly His Glu Val Pro 980 985 990 Gly Thr Gln Thr Pro Pro Gly Ser Thr Pro Pro His Cys Gly Pro Ser 995 1000 1005 Pro Glu Pro Thr Gln Arg Pro Pro Thr Ile Cys Glu Arg Trp Arg Glu 1010 1015 1020 Asn Leu Leu Glu His Tyr Gly Gly Thr Pro Arg Asp Asp Gln Tyr Val 1025 1030 1035 1040 Pro Gln Cys Asp Asp Leu Gly His Phe Ile Pro Leu Gln Cys His Gly 1045 1050 1055 Lys Ser Asp Phe Cys Trp Cys Val Asp Lys Asp Gly Arg Glu Val Gln 1060 1065 1070 Gly Thr Arg Ser Gln Pro Gly Thr Thr Pro Ala Cys Ile Pro Thr Val 1075 1080 1085 Ala Pro Pro Met Val Arg Pro Thr Pro Arg Pro Asp Val Thr Pro Pro 1090 1095 1100 Ser Val Gly Thr Phe Leu Leu Tyr Thr Gln Gly Gln Gln Ile Gly Tyr 1105 1110 1115 1120 Leu Pro Leu Asn Gly Thr Arg Leu Gln Lys Asp Ala Ala Lys Thr Leu 1125 1130 1135 Leu Ser Leu His Gly Ser Ile Ile Val Gly Ile Asp Tyr Asp Cys Arg 1140 1145 1150 Glu Arg Met Val Tyr Trp Thr Asp Val Ala Gly Arg Thr Ile Ser Arg 1155 1160 1165 Ala Gly Leu Glu Leu Gly Ala Glu Pro Glu Thr Ile Val Asn Ser Gly 1170 1175 1180 Leu Ile Ser Pro Glu Gly Leu Ala Ile Asp His Ile Arg Arg Thr Met 1185 1190 1195 1200 Tyr Trp Thr Asp Ser Val Leu Asp Lys Ile Glu Ser Ala Leu Leu Asp 1205 1210 1215 Gly Ser Glu Arg Lys Val Leu Phe Tyr Thr Asp Leu Val Asn Pro Arg 1220 1225 1230 Ala Ile Ala Val Asp Pro Ile Arg Gly Asn Leu Tyr Trp Thr Asp Trp 1235 1240 1245 Asn Arg Glu Ala Pro Lys Ile Glu Thr Ser Ser Leu Asp Gly Glu Asn 1250 1255 1260 Arg Arg Ile Leu Ile Asn Thr Asp Ile Gly Leu Pro Asn Gly Leu Thr 1265 1270 1275 1280 Phe Asp Pro Phe Ser Lys Leu Leu Cys Trp Ala Asp Ala Gly Thr Lys 1285 1290 1295 Lys Leu Glu Cys Thr Leu Pro Asp Gly Thr Gly Arg Arg Val Ile Gln 1300 1305 1310 Asn Asn Leu Lys Tyr Pro Phe Ser Ile Val Ser Tyr Ala Asp His Phe 1315 1320 1325 Tyr His Thr Asp Trp Arg Arg Asp Gly Val Val Ser Val Asn Lys His 1330 1335 1340 Ser Gly Gln Phe Thr Asp Glu Tyr Leu Pro Glu Gln Arg Ser His Leu 1345 1350 1355 1360 Tyr Gly Ile Thr Ala Val Tyr Pro Tyr Cys Pro Thr Gly Arg Lys 1365 1370 1375 <210> 60 <211> 212 <212> PRT <213> Homo sapiens <400> 60 Met Gly Pro Gly Pro Arg Leu Leu Leu Pro Leu Val Leu Cys Val Gly 1 5 10 15 Leu Gly Ala Leu Val Phe Ser Ser Gly Ala Glu Gly Phe Arg Lys Arg 20 25 30 Gly Pro Ser Val Thr Ala Lys Val Phe Phe Asp Val Arg Ile Gly Asp 35 40 45 Lys Asp Val Gly Arg Ile Val Ile Gly Leu Phe Gly Lys Val Val Pro 50 55 60 Lys Thr Val Glu Asn Phe Val Ala Leu Ala Thr Gly Glu Lys Gly Tyr 65 70 75 80 Gly Tyr Lys Gly Ser Lys Phe His Arg Val Ile Lys Asp Phe Met Ile 85 90 95 Gln Gly Gly Asp Ile Thr Thr Gly Asp Gly Thr Gly Gly Val Ser Ile 100 105 110 Tyr Gly Glu Thr Phe Pro Asp Glu Asn Phe Lys Leu Lys His Tyr Gly 115 120 125 Ile Gly Trp Val Ser Met Ala Asn Ala Gly Pro Asp Thr Asn Gly Ser 130 135 140 Gln Phe Phe Ile Thr Leu Thr Lys Pro Thr Trp Leu Asp Gly Lys His 145 150 155 160 Val Val Phe Gly Lys Val Ile Asp Gly Met Thr Val Val His Ser Ile 165 170 175 Glu Leu Gln Ala Thr Asp Gly His Asp Arg Pro Leu Thr Asn Cys Ser 180 185 190 Ile Ile Asn Ser Gly Lys Ile Asp Val Lys Thr Pro Phe Val Val Glu 195 200 205 Ile Ala Asp Trp 210 <210> 61 <211> 186 <212> PRT <213> Homo sapiens <400> 61 Pro Val Asp Leu Ser Lys Trp Ser Gly Pro Leu Ser Leu Gln Glu Val 1 5 10 15 Asp Glu Gln Pro Gln His Pro Leu His Val Thr Tyr Ala Gly Ala Ala 20 25 30 Val Asp Glu Leu Gly Lys Val Leu Thr Pro Thr Gln Val Lys Asn Arg 35 40 45 Pro Thr Ser Ile Ser Trp Asp Gly Leu Asp Ser Gly Lys Leu Tyr Thr 50 55 60 Leu Val Leu Thr Asp Pro Asp Ala Pro Ser Arg Lys Asp Pro Lys Tyr 65 70 75 80 Arg Glu Trp His His Phe Leu Val Val Asn Met Lys Gly Asn Asp Ile 85 90 95 Ser Ser Gly Thr Val Leu Ser Asp Tyr Val Gly Ser Gly Pro Pro Lys 100 105 110 Gly Thr Gly Leu His Arg Tyr Val Trp Leu Val Tyr Glu Gln Asp Arg 115 120 125 Pro Leu Lys Cys Asp Glu Pro Ile Leu Ser Asn Arg Ser Gly Asp His 130 135 140 Arg Gly Lys Phe Lys Val Ala Ser Phe Arg Lys Lys Tyr Glu Leu Arg 145 150 155 160 Ala Pro Val Ala Gly Thr Cys Tyr Gln Ala Glu Trp Asp Asp Tyr Val 165 170 175 Pro Lys Leu Tyr Glu Gln Leu Ser Gly Lys 180 185 <210> 62 <211> 1482 <212> PRT <213> Homo sapiens <400> 62 Met Arg Lys Asp Arg Leu Leu His Leu Cys Leu Val Leu Leu Leu Ile 1 5 10 15 Leu Leu Ser Ala Ser Asp Ser Asn Ser Thr Glu Pro Gln Tyr Met Val 20 25 30 Leu Val Pro Ser Leu Leu His Thr Glu Ala Pro Lys Lys Gly Cys Val 35 40 45 Leu Leu Ser His Leu Asn Glu Thr Val Thr Val Ser Ala Ser Leu Glu 50 55 60 Ser Gly Arg Glu Asn Arg Ser Leu Phe Thr Asp Leu Val Ala Glu Lys 65 70 75 80 Asp Leu Phe His Cys Val Ser Phe Thr Leu Pro Arg Ile Ser Ala Ser 85 90 95 Ser Glu Val Ala Phe Leu Ser Ile Gln Ile Lys Gly Pro Thr Gln Asp 100 105 110 Phe Arg Lys Arg Asn Thr Val Leu Val Leu Asn Thr Gln Ser Leu Val 115 120 125 Phe Val Gln Thr Asp Lys Pro Met Tyr Lys Pro Gly Gln Thr Val Arg 130 135 140 Phe Arg Val Val Ser Val Asp Glu Asn Phe Arg Pro Arg Asn Glu Leu 145 150 155 160 Ile Pro Leu Ile Tyr Leu Glu Asn Pro Arg Arg Asn Arg Ile Ala Gln 165 170 175 Trp Gln Ser Leu Lys Leu Glu Ala Gly Ile Asn Gln Leu Ser Phe Pro 180 185 190 Leu Ser Ser Glu Pro Ile Gln Gly Ser Tyr Arg Val Val Val Gln Thr 195 200 205 Glu Ser Gly Gly Arg Ile Gln His Pro Phe Thr Val Glu Glu Phe Val 210 215 220 Leu Pro Lys Phe Glu Val Lys Val Gln Val Pro Lys Ile Ile Ser Ile 225 230 235 240 Met Asp Glu Lys Val Asn Ile Thr Val Cys Gly Glu Tyr Thr Tyr Gly 245 250 255 Lys Pro Val Pro Gly Leu Ala Thr Val Ser Leu Cys Arg Lys Leu Ser 260 265 270 Arg Val Leu Asn Cys Asp Lys Gln Glu Val Cys Glu Glu Phe Ser Gln 275 280 285 Gln Leu Asn Ser Asn Gly Cys Ile Thr Gln Gln Val His Thr Lys Met 290 295 300 Leu Gln Ile Thr Asn Thr Gly Phe Glu Met Lys Leu Arg Val Glu Ala 305 310 315 320 Arg Ile Arg Glu Glu Gly Thr Asp Leu Glu Val Thr Ala Asn Arg Ile 325 330 335 Ser Glu Ile Thr Asn Ile Val Ser Lys Leu Lys Phe Val Lys Val Asp 340 345 350 Ser His Phe Arg Gln Gly Ile Pro Phe Phe Ala Gln Val Leu Leu Val 355 360 365 Asp Gly Lys Gly Val Pro Ile Pro Asn Lys Leu Phe Phe Ile Ser Val 370 375 380 Asn Asp Ala Asn Tyr Tyr Ser Asn Ala Thr Thr Asn Glu Gln Gly Leu 385 390 395 400 Ala Gln Phe Ser Ile Asn Thr Thr Ser Ile Ser Val Asn Lys Leu Phe 405 410 415 Val Arg Val Phe Thr Val His Pro Asn Leu Cys Phe His Tyr Ser Trp 420 425 430 Val Ala Glu Asp His Gln Gly Ala Gln His Thr Ala Asn Arg Val Phe 435 440 445 Ser Leu Ser Gly Ser Tyr Ile His Leu Glu Pro Val Ala Gly Thr Leu 450 455 460 Pro Cys Gly His Thr Glu Thr Ile Thr Ala His Tyr Thr Leu Asn Arg 465 470 475 480 Gln Ala Met Gly Glu Leu Ser Glu Leu Ser Phe His Tyr Leu Ile Met 485 490 495 Ala Lys Gly Val Ile Val Arg Ser Gly Thr His Thr Leu Pro Val Glu 500 505 510 Ser Gly Asp Met Lys Gly Ser Phe Ala Leu Ser Phe Pro Val Glu Ser 515 520 525 Asp Val Ala Pro Ile Ala Arg Met Phe Ile Phe Ala Ile Leu Pro Asp 530 535 540 Gly Glu Val Val Gly Asp Ser Glu Lys Phe Glu Ile Glu Asn Cys Leu 545 550 555 560 Ala Asn Lys Val Asp Leu Ser Phe Ser Pro Ala Gln Ser Pro Pro Ala 565 570 575 Ser His Ala His Leu Gln Val Ala Ala Ala Pro Gln Ser Leu Cys Ala 580 585 590 Leu Arg Ala Val Asp Gln Ser Val Leu Leu Met Lys Pro Glu Ala Glu 595 600 605 Leu Ser Val Ser Ser Val Tyr Asn Leu Leu Thr Val Lys Asp Leu Thr 610 615 620 Asn Phe Pro Asp Asn Val Asp Gln Gln Glu Glu Glu Gln Gly His Cys 625 630 635 640 Pro Arg Pro Phe Phe Ile His Asn Gly Ala Ile Tyr Val Pro Leu Ser 645 650 655 Ser Asn Glu Ala Asp Ile Tyr Ser Phe Leu Lys Gly Met Gly Leu Lys 660 665 670 Val Phe Thr Asn Ser Lys Ile Arg Lys Pro Lys Ser Cys Ser Val Ile 675 680 685 Pro Ser Val Ser Ala Gly Ala Val Gly Gln Gly Tyr Tyr Gly Ala Gly 690 695 700 Leu Gly Val Val Glu Arg Pro Tyr Val Pro Gln Leu Gly Thr Tyr Asn 705 710 715 720 Val Ile Pro Leu Asn Asn Glu Gln Ser Ser Gly Pro Val Pro Glu Thr 725 730 735 Val Arg Ser Tyr Phe Pro Glu Thr Trp Ile Trp Glu Leu Val Ala Val 740 745 750 Asn Ser Ser Gly Val Ala Glu Val Gly Val Thr Val Pro Asp Thr Ile 755 760 765 Thr Glu Trp Lys Ala Gly Ala Phe Cys Leu Ser Glu Asp Ala Gly Leu 770 775 780 Gly Ile Ser Ser Thr Ala Ser Leu Arg Ala Phe Gln Pro Phe Phe Val 785 790 795 800 Glu Leu Thr Met Pro Tyr Ser Val Ile Arg Gly Glu Val Phe Thr Leu 805 810 815 Lys Ala Thr Val Leu Asn Tyr Leu Pro Lys Cys Ile Arg Val Ser Val 820 825 830 Gln Leu Lys Ala Ser Pro Ala Phe Leu Ala Ser Gln Asn Thr Lys Gly 835 840 845 Glu Glu Ser Tyr Cys Ile Cys Gly Ser Glu Arg Gln Thr Leu Ser Trp 850 855 860 Thr Val Thr Pro Lys Thr Leu Gly Asn Val Asn Phe Ser Val Ser Ala 865 870 875 880 Glu Ala Met Gln Ser Leu Glu Leu Cys Gly Asn Glu Val Val Glu Val 885 890 895 Pro Glu Ile Lys Arg Lys Asp Thr Val Ile Lys Thr Leu Leu Val Glu 900 905 910 Ala Glu Gly Ile Glu Gln Glu Lys Thr Phe Ser Ser Met Thr Cys Ala 915 920 925 Ser Gly Ala Asn Val Ser Glu Gln Leu Ser Leu Lys Leu Pro Ser Asn 930 935 940 Val Val Lys Glu Ser Ala Arg Ala Ser Phe Ser Val Leu Gly Asp Ile 945 950 955 960 Leu Gly Ser Ala Met Gln Asn Ile Gln Asn Leu Leu Gln Met Pro Tyr 965 970 975 Gly Cys Gly Glu Gln Asn Met Val Leu Phe Ala Pro Asn Ile Tyr Val 980 985 990 Leu Asn Tyr Leu Asn Glu Thr Gln Gln Leu Thr Gln Glu Ile Lys Ala 995 1000 1005 Lys Ala Val Gly Tyr Leu Ile Thr Gly Tyr Gln Arg Gln Leu Asn Tyr 1010 1015 1020 Lys His Gln Asp Gly Ser Tyr Ser Thr Phe Gly Glu Arg Tyr Gly Arg 1025 1030 1035 1040 Asn Gln Gly Asn Thr Trp Leu Thr Ala Phe Val Leu Lys Thr Phe Ala 1045 1050 1055 Gln Ala Arg Ser Tyr Ile Phe Ile Asp Glu Ala His Ile Thr Gln Ser 1060 1065 1070 Leu Thr Trp Leu Ser Gln Met Gln Lys Asp Asn Gly Cys Phe Arg Ser 1075 1080 1085 Ser Gly Ser Leu Leu Asn Asn Ala Ile Lys Gly Gly Val Glu Asp Glu 1090 1095 1100 Ala Thr Leu Ser Ala Tyr Val Thr Ile Ala Leu Leu Glu Ile Pro Leu 1105 1110 1115 1120 Pro Val Thr Asn Pro Ile Val Arg Asn Ala Leu Phe Cys Leu Glu Ser 1125 1130 1135 Ala Trp Asn Val Ala Lys Glu Gly Thr His Gly Ser His Val Tyr Thr 1140 1145 1150 Lys Ala Leu Leu Ala Tyr Ala Phe Ser Leu Leu Gly Lys Gln Asn Gln 1155 1160 1165 Asn Arg Glu Ile Leu Asn Ser Leu Asp Lys Glu Ala Val Lys Glu Asp 1170 1175 1180 Asn Leu Val His Trp Glu Arg Pro Gln Arg Pro Lys Ala Pro Val Gly 1185 1190 1195 1200 His Leu Tyr Gln Thr Gln Ala Pro Ser Ala Glu Val Glu Met Thr Ser 1205 1210 1215 Tyr Val Leu Leu Ala Tyr Leu Thr Ala Gln Pro Ala Pro Thr Ser Gly 1220 1225 1230 Asp Leu Thr Ser Ala Thr Asn Ile Val Lys Trp Ile Met Lys Gln Gln 1235 1240 1245 Asn Ala Gln Gly Gly Phe Ser Ser Thr Gln Asp Thr Val Val Ala Leu 1250 1255 1260 His Ala Leu Ser Arg Tyr Gly Ala Ala Thr Phe Thr Arg Thr Glu Lys 1265 1270 1275 1280 Thr Ala Gln Val Thr Val Gln Asp Ser Gln Thr Phe Ser Thr Asn Phe 1285 1290 1295 Gln Val Asp Asn Asn Asn Leu Leu Leu Leu Gln Gln Ile Ser Leu Pro 1300 1305 1310 Glu Leu Pro Gly Glu Tyr Val Ile Thr Val Thr Gly Glu Arg Cys Val 1315 1320 1325 Tyr Leu Gln Thr Ser Met Lys Tyr Asn Ile Leu Pro Glu Lys Glu Asp 1330 1335 1340 Ser Pro Phe Ala Leu Lys Val Gln Thr Val Pro Gln Thr Cys Asp Gly 1345 1350 1355 1360 His Lys Ala His Thr Ser Phe Gln Ile Ser Leu Thr Ile Ser Tyr Thr 1365 1370 1375 Gly Asn Arg Pro Ala Ser Asn Met Val Ile Val Asp Val Lys Met Val 1380 1385 1390 Ser Gly Phe Ile Pro Leu Lys Pro Thr Val Lys Met Leu Glu Arg Ser 1395 1400 1405 Ser Ser Val Ser Arg Thr Glu Val Ser Asn Asn His Val Leu Ile Tyr 1410 1415 1420 Val Glu Gln Val Thr Asn Gln Thr Leu Ser Phe Ser Phe Met Val Leu 1425 1430 1435 1440 Gln Asp Ile Pro Val Gly Asp Leu Lys Pro Ala Ile Val Lys Val Tyr 1445 1450 1455 Asp Tyr Tyr Glu Thr Asp Glu Ser Val Val Ala Glu Tyr Ile Ala Pro 1460 1465 1470 Cys Ser Thr Asp Thr Glu His Gly Asn Val 1475 1480 <210> 63 <211> 189 <212> PRT <213> Homo sapiens <400> 63 Met Ala Ser Lys Arg Ala Leu Val Ile Leu Ala Lys Gly Ala Glu Glu 1 5 10 15 Met Glu Thr Val Ile Pro Val Asp Val Met Arg Arg Ala Gly Ile Lys 20 25 30 Val Thr Val Ala Gly Leu Ala Gly Lys Asp Pro Val Gln Cys Ser Arg 35 40 45 Asp Val Val Ile Cys Pro Asp Ala Ser Leu Glu Asp Ala Lys Lys Glu 50 55 60 Gly Pro Tyr Asp Val Val Val Leu Pro Gly Gly Asn Leu Gly Ala Gln 65 70 75 80 Asn Leu Ser Glu Ser Ala Ala Val Lys Glu Ile Leu Lys Glu Gln Glu 85 90 95 Asn Arg Lys Gly Leu Ile Ala Ala Ile Cys Ala Gly Pro Thr Ala Leu 100 105 110 Leu Ala His Glu Ile Gly Phe Gly Ser Lys Val Thr Thr His Pro Leu 115 120 125 Ala Lys Asp Lys Met Met Asn Gly Gly His Tyr Thr Tyr Ser Glu Asn 130 135 140 Arg Val Glu Lys Asp Gly Leu Ile Leu Thr Ser Arg Gly Pro Gly Thr 145 150 155 160 Ser Phe Glu Phe Ala Leu Ala Ile Val Glu Ala Leu Asn Gly Lys Glu 165 170 175 Val Ala Ala Gln Val Lys Ala Pro Leu Val Leu Lys Asp 180 185 <210> 64 <211> 185 <212> PRT <213> Homo sapiens <400> 64 Leu Val Ala Ala Met Thr Thr Ala Ser Thr Ser Gln Val Arg Gln Asn 1 5 10 15 Tyr His Gln Asp Ser Glu Ala Ala Ile Asn Gly Gln Ile Asn Leu Glu 20 25 30 Leu Tyr Ala Ser Tyr Val Tyr Leu Ser Val Ser Tyr Asn Phe Asp Arg 35 40 45 Asp Asp Val Ala Leu Arg Asn Phe Ala Thr Tyr Phe Leu His Gln Ser 50 55 60 His Glu Glu Arg Glu His Ala Glu Lys Leu Met Lys Leu Gln Asn Tyr 65 70 75 80 Arg Gly Gly Gln Ile Phe Leu Gln Asp Ile Lys Lys Pro Val Cys Asp 85 90 95 Asp Trp Glu Ser Gly Leu Asn Ala Met Glu Cys Ala Ser His Leu Glu 100 105 110 Lys Asn Val Asn Gln Ser Leu Leu Glu Leu His Lys Leu Ala Thr Asp 115 120 125 Lys Asn Asp Pro His Leu Cys Asp Phe Ile Glu Thr Cys Tyr Leu Asn 130 135 140 Glu Gln Val Lys Ala Ile Lys Glu Leu Gly Asp His Val Thr Asn Leu 145 150 155 160 His Lys Met Gly Ala Pro Glu Ser Gly Leu Ala Glu Tyr Ile Phe Asn 165 170 175 Lys Asn Thr Leu Gly Asp Ser Asp Asn 180 185 <210> 65 <211> 200 <212> PRT <213> Homo sapiens <400> 65 Thr Glu Lys Ala Pro Glu Pro His Val Glu Glu Asp Asp Asp Asp Glu 1 5 10 15 Leu Asp Ser Lys Leu Asn Tyr Lys Pro Pro Pro Gln Lys Ser Leu Lys 20 25 30 Glu Leu Gln Glu Met Asp Lys Asp Asp Glu Ser Leu Ile Lys Tyr Lys 35 40 45 Lys Thr Leu Leu Gly Asp Gly Pro Val Val Thr Asp Pro Lys Ala Pro 50 55 60 Asn Val Val Val Thr Arg Leu Thr Leu Val Cys Glu Ser Ala Pro Gly 65 70 75 80 Pro Ile Thr Met Asp Leu Thr Gly Asp Leu Glu Ala Leu Lys Lys Glu 85 90 95 Thr Ile Val Leu Lys Glu Gly Ser Glu Tyr Arg Val Lys Ile His Phe 100 105 110 Lys Val Asn Arg Asp Ile Val Ser Gly Leu Lys Tyr Val Gln His Thr 115 120 125 Tyr Arg Thr Gly Val Lys Val Asp Lys Ala Thr Phe Met Val Gly Ser 130 135 140 Tyr Gly Pro Arg Pro Glu Glu Tyr Glu Phe Leu Thr Pro Val Glu Glu 145 150 155 160 Ala Pro Lys Gly Met Leu Ala Arg Gly Thr Tyr His Asn Lys Ser Phe 165 170 175 Phe Thr Asp Asp Asp Lys Gln Asp His Leu Ser Trp Glu Trp Asn Leu 180 185 190 Ser Ile Lys Lys Glu Trp Thr Glu 195 200 <210> 66 <211> 390 <212> PRT <213> Homo sapiens <400> 66 Met Asn Ser Leu Ser Glu Ala Asn Thr Lys Phe Met Phe Asp Leu Phe 1 5 10 15 Gln Gln Phe Arg Lys Ser Lys Glu Asn Asn Ile Phe Tyr Ser Pro Ile 20 25 30 Ser Ile Thr Ser Ala Leu Gly Met Val Leu Leu Gly Ala Lys Asp Asn 35 40 45 Thr Ala Gln Gln Ile Ser Lys Val Leu His Phe Asp Gln Val Thr Glu 50 55 60 Asn Thr Thr Glu Lys Ala Ala Thr Tyr His Val Asp Arg Ser Gly Asn 65 70 75 80 Val His His Gln Phe Gln Lys Leu Leu Thr Glu Phe Asn Lys Ser Thr 85 90 95 Asp Ala Tyr Glu Leu Lys Ile Ala Asn Lys Leu Phe Gly Glu Lys Thr 100 105 110 Tyr Gln Phe Leu Gln Glu Tyr Leu Asp Ala Ile Lys Lys Phe Tyr Gln 115 120 125 Thr Ser Val Glu Ser Thr Asp Phe Ala Asn Ala Pro Glu Glu Ser Arg 130 135 140 Lys Lys Ile Asn Ser Trp Val Glu Ser Gln Thr Asn Glu Lys Ile Lys 145 150 155 160 Asn Leu Phe Pro Asp Gly Thr Ile Gly Asn Asp Thr Thr Leu Val Leu 165 170 175 Val Asn Ala Ile Tyr Phe Lys Gly Gln Trp Glu Asn Lys Phe Lys Lys 180 185 190 Glu Asn Thr Lys Glu Glu Lys Phe Trp Pro Asn Lys Asn Thr Tyr Lys 195 200 205 Ser Val Gln Met Met Arg Gln Tyr Asn Ser Phe Asn Phe Ala Leu Leu 210 215 220 Glu Asp Val Gln Ala Lys Val Leu Glu Ile Pro Tyr Lys Gly Lys Asp 225 230 235 240 Leu Ser Met Ile Val Leu Leu Pro Asn Glu Ile Asp Gly Leu Gln Lys 245 250 255 Leu Glu Glu Lys Leu Thr Ala Glu Lys Leu Met Glu Trp Thr Ser Leu 260 265 270 Gln Asn Met Arg Glu Thr Cys Val Asp Leu His Leu Pro Arg Phe Lys 275 280 285 Met Glu Glu Ser Tyr Asp Leu Lys Asp Thr Leu Arg Thr Met Gly Met 290 295 300 Val Asn Ile Phe Asn Gly Asp Ala Asp Leu Ser Gly Met Thr Trp Ser 305 310 315 320 His Gly Leu Ser Val Ser Lys Val Leu His Lys Ala Phe Val Glu Val 325 330 335 Thr Glu Glu Gly Val Glu Ala Ala Ala Ala Thr Ala Val Val Val Val 340 345 350 Glu Leu Ser Ser Pro Ser Thr Asn Glu Glu Phe Cys Cys Asn His Pro 355 360 365 Phe Leu Phe Phe Ile Arg Gln Asn Lys Thr Asn Ser Ile Leu Phe Tyr 370 375 380 Gly Arg Phe Ser Ser Pro 385 390 <210> 67 <211> 222 <212> PRT <213> Homo sapiens <400> 67 Met Leu Ser Arg Ala Val Cys Gly Thr Ser Arg Gln Leu Ala Pro Ala 1 5 10 15 Leu Gly Tyr Leu Gly Ser Arg Gln Lys His Ser Leu Pro Asp Leu Pro 20 25 30 Tyr Asp Tyr Gly Ala Leu Glu Pro His Ile Asn Ala Gln Ile Met Gln 35 40 45 Leu His His Ser Lys His His Ala Ala Tyr Val Asn Asn Leu Asn Val 50 55 60 Thr Glu Glu Lys Tyr Gln Glu Ala Leu Ala Lys Gly Asp Val Thr Ala 65 70 75 80 Gln Ile Ala Leu Gln Pro Ala Leu Lys Phe Asn Gly Gly Gly His Ile 85 90 95 Asn His Ser Ile Phe Trp Thr Asn Leu Ser Pro Asn Gly Gly Gly Glu 100 105 110 Pro Lys Gly Glu Leu Leu Glu Ala Ile Lys Arg Asp Phe Gly Ser Phe 115 120 125 Asp Lys Phe Lys Glu Lys Leu Thr Ala Ala Ser Val Gly Val Gln Gly 130 135 140 Ser Gly Trp Gly Trp Leu Gly Phe Asn Lys Glu Arg Gly His Leu Gln 145 150 155 160 Ile Ala Ala Cys Pro Asn Gln Asp Pro Leu Gln Gly Thr Thr Gly Leu 165 170 175 Ile Pro Leu Leu Gly Ile Asp Val Trp Glu His Ala Tyr Tyr Leu Gln 180 185 190 Tyr Lys Asn Val Arg Pro Asp Tyr Leu Lys Ala Ile Trp Asn Val Ile 195 200 205 Asn Trp Glu Asn Val Thr Glu Arg Tyr Met Ala Cys Lys Lys 210 215 220 <210> 68 <211> 104 <212> PRT <213> Homo sapiens <400> 68 Val Lys Gln Ile Glu Ser Lys Thr Ala Phe Gln Glu Ala Leu Asp Ala 1 5 10 15 Ala Gly Asp Lys Leu Val Val Val Asp Phe Ser Ala Thr Trp Cys Gly 20 25 30 Pro Cys Lys Met Ile Lys Pro Phe Phe His Ser Leu Ser Glu Lys Tyr 35 40 45 Ser Asn Val Ile Phe Leu Glu Val Asp Val Asp Asp Cys Gln Asp Val 50 55 60 Ala Ser Glu Cys Glu Val Lys Cys Met Pro Thr Phe Gln Phe Phe Lys 65 70 75 80 Lys Gly Gln Lys Val Gly Glu Phe Ser Gly Ala Asn Lys Glu Lys Leu 85 90 95 Glu Ala Thr Ile Asn Glu Leu Val 100 <210> 69 <211> 415 <212> PRT <213> Homo sapiens <400> 69 Met Ser Pro Phe Leu Tyr Leu Val Leu Leu Val Leu Gly Leu His Ala 1 5 10 15 Thr Ile His Cys Ala Ser Pro Glu Gly Lys Val Thr Ala Cys His Ser 20 25 30 Ser Gln Pro Asn Ala Thr Leu Tyr Lys Met Ser Ser Ile Asn Ala Asp 35 40 45 Phe Ala Phe Asn Leu Tyr Arg Arg Phe Thr Val Glu Thr Pro Asp Lys 50 55 60 Asn Ile Phe Phe Ser Pro Val Ser Ile Ser Ala Ala Leu Val Met Leu 65 70 75 80 Ser Phe Gly Ala Cys Cys Ser Thr Gln Thr Glu Ile Val Glu Thr Leu 85 90 95 Gly Phe Asn Leu Thr Asp Thr Pro Met Val Glu Ile Gln His Gly Phe 100 105 110 Gln His Leu Ile Cys Ser Leu Asn Phe Pro Lys Lys Glu Leu Glu Leu 115 120 125 Gln Ile Gly Asn Ala Leu Phe Ile Gly Lys His Leu Lys Pro Leu Ala 130 135 140 Lys Phe Leu Asn Asp Val Lys Thr Leu Tyr Glu Thr Glu Val Phe Ser 145 150 155 160 Thr Asp Phe Ser Asn Ile Ser Ala Ala Lys Gln Glu Ile Asn Ser His 165 170 175 Val Glu Met Gln Thr Lys Gly Lys Val Val Gly Leu Ile Gln Asp Leu 180 185 190 Lys Pro Asn Thr Ile Met Val Leu Val Asn Tyr Ile His Phe Lys Ala 195 200 205 Gln Trp Ala Asn Pro Phe Asp Pro Ser Lys Thr Glu Asp Ser Ser Ser 210 215 220 Phe Leu Ile Asp Lys Thr Thr Thr Val Gln Val Pro Met Met His Gln 225 230 235 240 Met Glu Gln Tyr Tyr His Leu Val Asp Met Glu Leu Asn Cys Thr Val 245 250 255 Leu Gln Met Asp Tyr Ser Lys Asn Ala Leu Ala Leu Phe Val Leu Pro 260 265 270 Lys Glu Gly Gln Met Glu Ser Val Glu Ala Ala Met Ser Ser Lys Thr 275 280 285 Leu Lys Lys Trp Asn Arg Leu Leu Gln Lys Gly Trp Val Asp Leu Phe 290 295 300 Val Pro Lys Phe Ser Ile Ser Ala Thr Tyr Asp Leu Gly Ala Thr Leu 305 310 315 320 Leu Lys Met Gly Ile Gln His Ala Tyr Ser Glu Asn Ala Asp Phe Ser 325 330 335 Gly Leu Thr Glu Asp Asn Gly Leu Lys Leu Ser Asn Ala Ala His Lys 340 345 350 Ala Val Leu His Ile Gly Glu Lys Gly Thr Glu Ala Ala Ala Val Pro 355 360 365 Glu Val Glu Leu Ser Asp Gln Pro Glu Asn Thr Phe Leu His Pro Ile 370 375 380 Ile Gln Ile Asp Arg Ser Phe Met Leu Leu Ile Leu Glu Arg Ser Thr 385 390 395 400 Arg Ser Ile Leu Phe Leu Gly Lys Val Val Asn Pro Thr Glu Ala 405 410 415 <210> 70 <211> 286 <212> PRT <213> Homo sapiens <400> 70 Met Ala Glu Asp Gly Glu Glu Ala Glu Phe His Phe Ala Ala Leu Tyr 1 5 10 15 Ile Ser Gly Gln Trp Pro Arg Leu Arg Ala Asp Thr Asp Leu Gln Arg 20 25 30 Leu Gly Ser Ser Ala Met Ala Pro Ser Arg Lys Phe Phe Val Gly Gly 35 40 45 Asn Trp Lys Met Asn Gly Arg Lys Gln Ser Leu Gly Glu Leu Ile Gly 50 55 60 Thr Leu Asn Ala Ala Lys Val Pro Ala Asp Thr Glu Val Val Cys Ala 65 70 75 80 Pro Pro Thr Ala Tyr Ile Asp Phe Ala Arg Gln Lys Leu Asp Pro Lys 85 90 95 Ile Ala Val Ala Ala Gln Asn Cys Tyr Lys Val Thr Asn Gly Ala Phe 100 105 110 Thr Gly Glu Ile Ser Pro Gly Met Ile Lys Asp Cys Gly Ala Thr Trp 115 120 125 Val Val Leu Gly His Ser Glu Arg Arg His Val Phe Gly Glu Ser Asp 130 135 140 Glu Leu Ile Gly Gln Lys Val Ala His Ala Leu Ala Glu Gly Leu Gly 145 150 155 160 Val Ile Ala Cys Ile Gly Glu Lys Leu Asp Glu Arg Glu Ala Gly Ile 165 170 175 Thr Glu Lys Val Val Phe Glu Gln Thr Lys Val Ile Ala Asp Asn Val 180 185 190 Lys Asp Trp Ser Lys Val Val Leu Ala Tyr Glu Pro Val Trp Ala Ile 195 200 205 Gly Thr Gly Lys Thr Ala Thr Pro Gln Gln Ala Gln Glu Val His Glu 210 215 220 Lys Leu Arg Gly Trp Leu Lys Ser Asn Val Ser Asp Ala Val Ala Gln 225 230 235 240 Ser Thr Arg Ile Ile Tyr Gly Gly Ser Val Thr Gly Ala Thr Cys Lys 245 250 255 Glu Leu Ala Ser Gln Pro Asp Val Asp Gly Phe Leu Val Gly Gly Ala 260 265 270 Ser Leu Lys Pro Glu Phe Val Asp Ile Ile Asn Ala Lys Gln 275 280 285 <210> 71 <211> 188 <212> PRT <213> Homo sapiens <400> 71 Met Ala Asn Ser Gly Cys Lys Asp Val Thr Gly Pro Asp Glu Glu Ser 1 5 10 15 Phe Leu Tyr Phe Ala Tyr Gly Ser Asn Leu Leu Thr Glu Arg Ile His 20 25 30 Leu Arg Asn Pro Ser Ala Ala Phe Phe Cys Val Ala Arg Leu Gln Asp 35 40 45 Phe Lys Leu Asp Phe Gly Asn Ser Gln Gly Lys Thr Ser Gln Thr Trp 50 55 60 His Gly Gly Ile Ala Thr Ile Phe Gln Ser Pro Gly Asp Glu Val Trp 65 70 75 80 Gly Val Val Trp Lys Met Asn Lys Ser Asn Leu Asn Ser Leu Asp Glu 85 90 95 Gln Glu Gly Val Lys Ser Gly Met Tyr Val Val Ile Glu Val Lys Val 100 105 110 Ala Thr Gln Glu Gly Lys Glu Ile Thr Cys Arg Ser Tyr Leu Met Thr 115 120 125 Asn Tyr Glu Ser Ala Pro Pro Ser Pro Gln Tyr Lys Lys Ile Ile Cys 130 135 140 Met Gly Ala Lys Glu Asn Gly Leu Pro Leu Glu Tyr Gln Glu Lys Leu 145 150 155 160 Lys Ala Ile Glu Pro Asn Asp Tyr Thr Gly Lys Val Ser Glu Glu Ile 165 170 175 Glu Asp Ile Ile Lys Lys Gly Glu Thr Gln Thr Leu 180 185 <210> 72 <211> 168 <212> PRT <213> Homo sapiens <400> 72 Met Ala Gly Phe Pro Leu Leu Leu Thr Leu Leu Thr His Cys Ala Gly 1 5 10 15 Ser Trp Ala Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr 20 25 30 Pro Gly Gln Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile 35 40 45 Gly Ser Asn Tyr Val Tyr Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro 50 55 60 Lys Leu Leu Ile Tyr Ser Asn Asn Gln Arg Pro Ser Gly Val Pro Asp 65 70 75 80 Arg Phe Ser Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser 85 90 95 Gly Leu Arg Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Ala Trp Asp 100 105 110 Asp Ser Leu Ser Gly Pro Thr Val Leu Gln Ala Gln Gly Glu Leu Arg 115 120 125 Gln Glu Pro Pro Ser Ser Ser Val Arg Arg Val Ser Pro Gly Ser Cys 130 135 140 Cys Ser Gly Pro Ala Cys Gly Phe Cys Cys Cys Ser Phe Pro His Gly 145 150 155 160 Ser Lys Gly Ile Gln Gly Pro Ala 165 <210> 73 <211> 99 <212> PRT <213> Homo sapiens <400> 73 Gln Ser Ala Leu Thr Gln Pro Pro Ser Val Ser Gly Ser Pro Gly Gln 1 5 10 15 Ser Val Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Ser Tyr 20 25 30 Asn Arg Val Ser Trp Tyr Gln Gln Pro Pro Gly Thr Ala Pro Lys Leu 35 40 45 Met Ile Tyr Glu Val Ser Asn Arg Pro Ser Gly Val Pro Asp Arg Phe 50 55 60 Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu 65 70 75 80 Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Leu Tyr Thr Ser Ser 85 90 95 Ser Thr Phe <210> 74 <211> 2813 <212> PRT <213> Homo sapiens <400> 74 Met Ile Pro Ala Arg Phe Ala Gly Val Leu Leu Ala Leu Ala Leu Ile 1 5 10 15 Leu Pro Gly Thr Leu Cys Ala Glu Gly Thr Arg Gly Arg Ser Ser Thr 20 25 30 Ala Arg Cys Ser Leu Phe Gly Ser Asp Phe Val Asn Thr Phe Asp Gly 35 40 45 Ser Met Tyr Ser Phe Ala Gly Tyr Cys Ser Tyr Leu Leu Ala Gly Gly 50 55 60 Cys Gln Lys Arg Ser Phe Ser Ile Ile Gly Asp Phe Gln Asn Gly Lys 65 70 75 80 Arg Val Ser Leu Ser Val Tyr Leu Gly Glu Phe Phe Asp Ile His Leu 85 90 95 Phe Val Asn Gly Thr Val Thr Gln Gly Asp Gln Arg Val Ser Met Pro 100 105 110 Tyr Ala Ser Lys Gly Leu Tyr Leu Glu Thr Glu Ala Gly Tyr Tyr Lys 115 120 125 Leu Ser Gly Glu Ala Tyr Gly Phe Val Ala Arg Ile Asp Gly Ser Gly 130 135 140 Asn Phe Gln Val Leu Leu Ser Asp Arg Tyr Phe Asn Lys Thr Cys Gly 145 150 155 160 Leu Cys Gly Asn Phe Asn Ile Phe Ala Glu Asp Asp Phe Met Thr Gln 165 170 175 Glu Gly Thr Leu Thr Ser Asp Pro Tyr Asp Phe Ala Asn Ser Trp Ala 180 185 190 Leu Ser Ser Gly Glu Gln Trp Cys Glu Arg Ala Ser Pro Pro Ser Ser 195 200 205 Ser Cys Asn Ile Ser Ser Gly Glu Met Gln Lys Gly Leu Trp Glu Gln 210 215 220 Cys Gln Leu Leu Lys Ser Thr Ser Val Phe Ala Arg Cys His Pro Leu 225 230 235 240 Val Asp Pro Glu Pro Phe Val Ala Leu Cys Glu Lys Thr Leu Cys Glu 245 250 255 Cys Ala Gly Gly Leu Glu Cys Ala Cys Pro Ala Leu Leu Glu Tyr Ala 260 265 270 Arg Thr Cys Ala Gln Glu Gly Met Val Leu Tyr Gly Trp Thr Asp His 275 280 285 Ser Ala Cys Ser Pro Val Cys Pro Ala Gly Met Glu Tyr Arg Gln Cys 290 295 300 Val Ser Pro Cys Ala Arg Thr Cys Gln Ser Leu His Ile Asn Glu Met 305 310 315 320 Cys Gln Glu Arg Cys Val Asp Gly Cys Ser Cys Pro Glu Gly Gln Leu 325 330 335 Leu Asp Glu Gly Leu Cys Val Glu Ser Thr Glu Cys Pro Cys Val His 340 345 350 Ser Gly Lys Arg Tyr Pro Pro Gly Thr Ser Leu Ser Arg Asp Cys Asn 355 360 365 Thr Cys Ile Cys Arg Asn Ser Gln Trp Ile Cys Ser Asn Glu Glu Cys 370 375 380 Pro Gly Glu Cys Leu Val Thr Gly Gln Ser His Phe Lys Ser Phe Asp 385 390 395 400 Asn Arg Tyr Phe Thr Phe Ser Gly Ile Cys Gln Tyr Leu Leu Ala Arg 405 410 415 Asp Cys Gln Asp His Ser Phe Ser Ile Val Ile Glu Thr Val Gln Cys 420 425 430 Ala Asp Asp Arg Asp Ala Val Cys Thr Arg Ser Val Thr Val Arg Leu 435 440 445 Pro Gly Leu His Asn Ser Leu Val Lys Leu Lys His Gly Ala Gly Val 450 455 460 Ala Met Asp Gly Gln Asp Ile Gln Leu Pro Leu Leu Lys Gly Asp Leu 465 470 475 480 Arg Ile Gln His Thr Val Thr Ala Ser Val Arg Leu Ser Tyr Gly Glu 485 490 495 Asp Leu Gln Met Asp Trp Asp Gly Arg Gly Arg Leu Leu Val Lys Leu 500 505 510 Ser Pro Val Tyr Ala Gly Lys Thr Cys Gly Leu Cys Gly Asn Tyr Asn 515 520 525 Gly Asn Gln Gly Asp Asp Phe Leu Thr Pro Ser Gly Leu Ala Glu Pro 530 535 540 Arg Val Glu Asp Phe Gly Asn Ala Trp Lys Leu His Gly Asp Cys Gln 545 550 555 560 Asp Leu Gln Lys Gln His Ser Asp Pro Cys Ala Leu Asn Pro Arg Met 565 570 575 Thr Arg Phe Ser Glu Glu Ala Cys Ala Val Leu Thr Ser Pro Thr Phe 580 585 590 Glu Ala Cys His Arg Ala Val Ser Pro Leu Pro Tyr Leu Arg Asn Cys 595 600 605 Arg Tyr Asp Val Cys Ser Cys Ser Asp Gly Arg Glu Cys Leu Cys Gly 610 615 620 Ala Leu Ala Ser Tyr Ala Ala Ala Cys Ala Gly Arg Gly Val Arg Val 625 630 635 640 Ala Trp Arg Glu Pro Gly Arg Cys Glu Leu Asn Cys Pro Lys Gly Gln 645 650 655 Val Tyr Leu Gln Cys Gly Thr Pro Cys Asn Leu Thr Cys Arg Ser Leu 660 665 670 Ser Tyr Pro Asp Glu Glu Cys Asn Glu Ala Cys Leu Glu Gly Cys Phe 675 680 685 Cys Pro Pro Gly Leu Tyr Met Asp Glu Arg Gly Asp Cys Val Pro Lys 690 695 700 Ala Gln Cys Pro Cys Tyr Tyr Asp Gly Glu Ile Phe Gln Pro Glu Asp 705 710 715 720 Ile Phe Ser Asp His His Thr Met Cys Tyr Cys Glu Asp Gly Phe Met 725 730 735 His Cys Thr Met Ser Gly Val Pro Gly Ser Leu Leu Pro Asp Ala Val 740 745 750 Leu Ser Ser Pro Leu Ser His Arg Ser Lys Arg Ser Leu Ser Cys Arg 755 760 765 Pro Pro Met Val Lys Leu Val Cys Pro Ala Asp Asn Leu Arg Ala Glu 770 775 780 Gly Leu Glu Cys Thr Lys Thr Cys Gln Asn Tyr Asp Leu Glu Cys Met 785 790 795 800 Ser Met Gly Cys Val Ser Gly Cys Leu Cys Pro Pro Gly Met Val Arg 805 810 815 His Glu Asn Arg Cys Val Ala Leu Glu Arg Cys Pro Cys Phe His Gln 820 825 830 Gly Lys Glu Tyr Ala Pro Gly Glu Thr Val Lys Ile Gly Cys Asn Thr 835 840 845 Cys Val Cys Arg Asp Arg Lys Trp Asn Cys Thr Asp His Val Cys Asp 850 855 860 Ala Thr Cys Ser Thr Ile Gly Met Ala His Tyr Leu Thr Phe Asp Gly 865 870 875 880 Leu Lys Tyr Leu Phe Pro Gly Glu Cys Gln Tyr Val Leu Val Gln Asp 885 890 895 Tyr Cys Gly Ser Asn Pro Gly Thr Phe Arg Ile Leu Val Gly Asn Lys 900 905 910 Gly Cys Ser His Pro Ser Val Lys Cys Lys Lys Arg Val Thr Ile Leu 915 920 925 Val Glu Gly Gly Glu Ile Glu Leu Phe Asp Gly Glu Val Asn Val Lys 930 935 940 Arg Pro Met Lys Asp Glu Thr His Phe Glu Val Val Glu Ser Gly Arg 945 950 955 960 Tyr Ile Ile Leu Leu Leu Gly Lys Ala Leu Ser Val Val Trp Asp Arg 965 970 975 His Leu Ser Ile Ser Val Val Leu Lys Gln Thr Tyr Gln Glu Lys Val 980 985 990 Cys Gly Leu Cys Gly Asn Phe Asp Gly Ile Gln Asn Asn Asp Leu Thr 995 1000 1005 Ser Ser Asn Leu Gln Val Glu Glu Asp Pro Val Asp Phe Gly Asn Ser 1010 1015 1020 Trp Lys Val Ser Ser Gln Cys Ala Asp Thr Arg Lys Val Pro Leu Asp 1025 1030 1035 1040 Ser Ser Pro Ala Thr Cys His Asn Asn Ile Met Lys Gln Thr Met Val 1045 1050 1055 Asp Ser Ser Cys Arg Ile Leu Thr Ser Asp Val Phe Gln Asp Cys Asn 1060 1065 1070 Lys Leu Val Asp Pro Glu Pro Tyr Leu Asp Val Cys Ile Tyr Asp Thr 1075 1080 1085 Cys Ser Cys Glu Ser Ile Gly Asp Cys Ala Cys Phe Cys Asp Thr Ile 1090 1095 1100 Ala Ala Tyr Ala His Val Cys Ala Gln His Gly Lys Val Val Thr Trp 1105 1110 1115 1120 Arg Thr Ala Thr Leu Cys Pro Gln Ser Cys Glu Glu Arg Asn Leu Arg 1125 1130 1135 Glu Asn Gly Tyr Glu Cys Glu Trp Arg Tyr Asn Ser Cys Ala Pro Ala 1140 1145 1150 Cys Gln Val Thr Cys Gln His Pro Glu Pro Leu Ala Cys Pro Val Gln 1155 1160 1165 Cys Val Glu Gly Cys His Ala His Cys Pro Pro Gly Lys Ile Leu Asp 1170 1175 1180 Glu Leu Leu Gln Thr Cys Val Asp Pro Glu Asp Cys Pro Val Cys Glu 1185 1190 1195 1200 Val Ala Gly Arg Arg Phe Ala Ser Gly Lys Lys Val Thr Leu Asn Pro 1205 1210 1215 Ser Asp Pro Glu His Cys Gln Ile Cys His Cys Asp Val Val Asn Leu 1220 1225 1230 Thr Cys Glu Ala Cys Gln Glu Pro Gly Gly Leu Val Val Pro Pro Thr 1235 1240 1245 Asp Ala Pro Val Ser Pro Thr Thr Leu Tyr Val Glu Asp Ile Ser Glu 1250 1255 1260 Pro Pro Leu His Asp Phe Tyr Cys Ser Arg Leu Leu Asp Leu Val Phe 1265 1270 1275 1280 Leu Leu Asp Gly Ser Ser Arg Leu Ser Glu Ala Glu Phe Glu Val Leu 1285 1290 1295 Lys Ala Phe Val Val Asp Met Met Glu Arg Leu Arg Ile Ser Gln Lys 1300 1305 1310 Trp Val Arg Val Ala Val Val Glu Tyr His Asp Gly Ser His Ala Tyr 1315 1320 1325 Ile Gly Leu Lys Asp Arg Lys Arg Pro Ser Glu Leu Arg Arg Ile Ala 1330 1335 1340 Ser Gln Val Lys Tyr Ala Gly Ser Gln Val Ala Ser Thr Ser Glu Val 1345 1350 1355 1360 Leu Lys Tyr Thr Leu Phe Gln Ile Phe Ser Lys Ile Asp Arg Pro Glu 1365 1370 1375 Ala Ser Arg Ile Ala Leu Leu Leu Met Ala Ser Gln Glu Pro Gln Arg 1380 1385 1390 Met Ser Arg Asn Phe Val Arg Tyr Val Gln Gly Leu Lys Lys Lys Lys 1395 1400 1405 Val Ile Val Ile Pro Val Gly Ile Gly Pro His Ala Asn Leu Lys Gln 1410 1415 1420 Ile Arg Leu Ile Glu Lys Gln Ala Pro Glu Asn Lys Ala Phe Val Leu 1425 1430 1435 1440 Ser Ser Val Asp Glu Leu Glu Gln Gln Arg Asp Glu Ile Val Ser Tyr 1445 1450 1455 Leu Cys Asp Leu Ala Pro Glu Ala Pro Pro Pro Thr Leu Pro Pro His 1460 1465 1470 Met Ala Gln Val Thr Val Gly Pro Gly Leu Leu Gly Val Ser Thr Leu 1475 1480 1485 Gly Pro Lys Arg Asn Ser Met Val Leu Asp Val Ala Phe Val Leu Glu 1490 1495 1500 Gly Ser Asp Lys Ile Gly Glu Ala Asp Phe Asn Arg Ser Lys Glu Phe 1505 1510 1515 1520 Met Glu Glu Val Ile Gln Arg Met Asp Val Gly Gln Asp Ser Ile His 1525 1530 1535 Val Thr Val Leu Gln Tyr Ser Tyr Met Val Thr Val Glu Tyr Pro Phe 1540 1545 1550 Ser Glu Ala Gln Ser Lys Gly Asp Ile Leu Gln Arg Val Arg Glu Ile 1555 1560 1565 Arg Tyr Gln Gly Gly Asn Arg Thr Asn Thr Gly Leu Ala Leu Arg Tyr 1570 1575 1580 Leu Ser Asp His Ser Phe Leu Val Ser Gln Gly Asp Arg Glu Gln Ala 1585 1590 1595 1600 Pro Asn Leu Val Tyr Met Val Thr Gly Asn Pro Ala Ser Asp Glu Ile 1605 1610 1615 Lys Arg Leu Pro Gly Asp Ile Gln Val Val Pro Ile Gly Val Gly Pro 1620 1625 1630 Asn Ala Asn Val Gln Glu Leu Glu Arg Ile Gly Trp Pro Asn Ala Pro 1635 1640 1645 Ile Leu Ile Gln Asp Phe Glu Thr Leu Pro Arg Glu Ala Pro Asp Leu 1650 1655 1660 Val Leu Gln Arg Cys Cys Ser Gly Glu Gly Leu Gln Ile Pro Thr Leu 1665 1670 1675 1680 Ser Pro Ala Pro Asp Cys Ser Gln Pro Leu Asp Val Ile Leu Leu Leu 1685 1690 1695 Asp Gly Ser Ser Ser Phe Pro Ala Ser Tyr Phe Asp Glu Met Lys Ser 1700 1705 1710 Phe Ala Lys Ala Phe Ile Ser Lys Ala Asn Ile Gly Pro Arg Leu Thr 1715 1720 1725 Gln Val Ser Val Leu Gln Tyr Gly Ser Ile Thr Thr Ile Asp Val Pro 1730 1735 1740 Trp Asn Val Val Pro Glu Lys Ala His Leu Leu Ser Leu Val Asp Val 1745 1750 1755 1760 Met Gln Arg Glu Gly Gly Pro Ser Gln Ile Gly Asp Ala Leu Gly Phe 1765 1770 1775 Ala Val Arg Tyr Leu Thr Ser Glu Met His Gly Ala Arg Pro Gly Ala 1780 1785 1790 Ser Lys Ala Val Val Ile Leu Val Thr Asp Val Ser Val Asp Ser Val 1795 1800 1805 Asp Ala Ala Ala Asp Ala Ala Arg Ser Asn Arg Val Thr Val Phe Pro 1810 1815 1820 Ile Gly Ile Gly Asp Arg Tyr Asp Ala Ala Gln Leu Arg Ile Leu Ala 1825 1830 1835 1840 Gly Pro Ala Gly Asp Ser Asn Val Val Lys Leu Gln Arg Ile Glu Asp 1845 1850 1855 Leu Pro Thr Met Val Thr Leu Gly Asn Ser Phe Leu His Lys Leu Cys 1860 1865 1870 Ser Gly Phe Val Arg Ile Cys Met Asp Glu Asp Gly Asn Glu Lys Arg 1875 1880 1885 Pro Gly Asp Val Trp Thr Leu Pro Asp Gln Cys His Thr Val Thr Cys 1890 1895 1900 Gln Pro Asp Gly Gln Thr Leu Leu Lys Ser His Arg Val Asn Cys Asp 1905 1910 1915 1920 Arg Gly Leu Arg Pro Ser Cys Pro Asn Ser Gln Ser Pro Val Lys Val 1925 1930 1935 Glu Glu Thr Cys Gly Cys Arg Trp Thr Cys Pro Cys Val Cys Thr Gly 1940 1945 1950 Ser Ser Thr Arg His Ile Val Thr Phe Asp Gly Gln Asn Phe Lys Leu 1955 1960 1965 Thr Gly Ser Cys Ser Tyr Val Leu Phe Gln Asn Lys Glu Gln Asp Leu 1970 1975 1980 Glu Val Ile Leu His Asn Gly Ala Cys Ser Pro Gly Ala Arg Gln Gly 1985 1990 1995 2000 Cys Met Lys Ser Ile Glu Val Lys His Ser Ala Leu Ser Val Glu Leu 2005 2010 2015 His Ser Asp Met Glu Val Thr Val Asn Gly Arg Leu Val Ser Val Pro 2020 2025 2030 Tyr Val Gly Gly Asn Met Glu Val Asn Val Tyr Gly Ala Ile Met His 2035 2040 2045 Glu Val Arg Phe Asn His Leu Gly His Ile Phe Thr Phe Thr Pro Gln 2050 2055 2060 Asn Asn Glu Phe Gln Leu Gln Leu Ser Pro Lys Thr Phe Ala Ser Lys 2065 2070 2075 2080 Thr Tyr Gly Leu Cys Gly Ile Cys Asp Glu Asn Gly Ala Asn Asp Phe 2085 2090 2095 Met Leu Arg Asp Gly Thr Val Thr Thr Asp Trp Lys Thr Leu Val Gln 2100 2105 2110 Glu Trp Thr Val Gln Arg Pro Gly Gln Thr Cys Gln Pro Ile Leu Glu 2115 2120 2125 Glu Gln Cys Leu Val Pro Asp Ser Ser His Cys Gln Val Leu Leu Leu 2130 2135 2140 Pro Leu Phe Ala Glu Cys His Lys Val Leu Ala Pro Ala Thr Phe Tyr 2145 2150 2155 2160 Ala Ile Cys Gln Gln Asp Ser Cys His Gln Glu Gln Val Cys Glu Val 2165 2170 2175 Ile Ala Ser Tyr Ala His Leu Cys Arg Thr Asn Gly Val Cys Val Asp 2180 2185 2190 Trp Arg Thr Pro Asp Phe Cys Ala Met Ser Cys Pro Pro Ser Leu Val 2195 2200 2205 Tyr Asn His Cys Glu His Gly Cys Pro Arg His Cys Asp Gly Asn Val 2210 2215 2220 Ser Ser Cys Gly Asp His Pro Ser Glu Gly Cys Phe Cys Pro Pro Asp 2225 2230 2235 2240 Lys Val Met Leu Glu Gly Ser Cys Val Pro Glu Glu Ala Cys Thr Gln 2245 2250 2255 Cys Ile Gly Glu Asp Gly Val Gln His Gln Phe Leu Glu Ala Trp Val 2260 2265 2270 Pro Asp His Gln Pro Cys Gln Ile Cys Thr Cys Leu Ser Gly Arg Lys 2275 2280 2285 Val Asn Cys Thr Thr Gln Pro Cys Pro Thr Ala Lys Ala Pro Thr Cys 2290 2295 2300 Gly Leu Cys Glu Val Ala Arg Leu Arg Gln Asn Ala Asp Gln Cys Cys 2305 2310 2315 2320 Pro Glu Tyr Glu Cys Val Cys Asp Pro Val Ser Cys Asp Leu Pro Pro 2325 2330 2335 Val Pro His Cys Glu Arg Gly Leu Gln Pro Thr Leu Thr Asn Pro Gly 2340 2345 2350 Glu Cys Arg Pro Asn Phe Thr Cys Ala Cys Arg Lys Glu Glu Cys Lys 2355 2360 2365 Arg Val Ser Pro Pro Ser Cys Pro Pro His Arg Leu Pro Thr Leu Arg 2370 2375 2380 Lys Thr Gln Cys Cys Asp Glu Tyr Glu Cys Ala Cys Asn Cys Val Asn 2385 2390 2395 2400 Ser Thr Val Ser Cys Pro Leu Gly Tyr Leu Ala Ser Thr Ala Thr Asn 2405 2410 2415 Asp Cys Gly Cys Thr Thr Thr Thr Cys Leu Pro Asp Lys Val Cys Val 2420 2425 2430 His Arg Ser Thr Ile Tyr Pro Val Gly Gln Phe Trp Glu Glu Gly Cys 2435 2440 2445 Asp Val Cys Thr Cys Thr Asp Met Glu Asp Ala Val Met Gly Leu Arg 2450 2455 2460 Val Ala Gln Cys Ser Gln Lys Pro Cys Glu Asp Ser Cys Arg Ser Gly 2465 2470 2475 2480 Phe Thr Tyr Val Leu His Glu Gly Glu Cys Cys Gly Arg Cys Leu Pro 2485 2490 2495 Ser Ala Cys Glu Val Val Thr Gly Ser Pro Arg Gly Asp Ser Gln Ser 2500 2505 2510 Ser Trp Lys Ser Val Gly Ser Gln Trp Ala Ser Pro Glu Asn Pro Cys 2515 2520 2525 Leu Ile Asn Glu Cys Val Arg Val Lys Glu Glu Val Phe Ile Gln Gln 2530 2535 2540 Arg Asn Val Ser Cys Pro Gln Leu Glu Val Pro Val Cys Pro Ser Gly 2545 2550 2555 2560 Phe Gln Leu Ser Cys Lys Thr Ser Ala Cys Cys Pro Ser Cys Arg Cys 2565 2570 2575 Glu Arg Met Glu Ala Cys Met Leu Asn Gly Thr Val Ile Gly Pro Gly 2580 2585 2590 Lys Thr Val Met Ile Asp Val Cys Thr Thr Cys Arg Cys Met Val Gln 2595 2600 2605 Val Gly Val Ile Ser Gly Phe Lys Leu Glu Cys Arg Lys Thr Thr Cys 2610 2615 2620 Asn Pro Cys Pro Leu Gly Tyr Lys Glu Glu Asn Asn Thr Gly Glu Cys 2625 2630 2635 2640 Cys Gly Arg Cys Leu Pro Thr Ala Cys Thr Ile Gln Leu Arg Gly Gly 2645 2650 2655 Gln Ile Met Thr Leu Lys Arg Asp Glu Thr Leu Gln Asp Gly Cys Asp 2660 2665 2670 Thr His Phe Cys Lys Val Asn Glu Arg Gly Glu Tyr Phe Trp Glu Lys 2675 2680 2685 Arg Val Thr Gly Cys Pro Pro Phe Asp Glu His Lys Cys Leu Ala Glu 2690 2695 2700 Gly Gly Lys Ile Met Lys Ile Pro Gly Thr Cys Cys Asp Thr Cys Glu 2705 2710 2715 2720 Glu Pro Glu Cys Asn Asp Ile Thr Ala Arg Leu Gln Tyr Val Lys Val 2725 2730 2735 Gly Ser Cys Lys Ser Glu Val Glu Val Asp Ile His Tyr Cys Gln Gly 2740 2745 2750 Lys Cys Ala Ser Lys Ala Met Tyr Ser Ile Asp Ile Asn Asp Val Gln 2755 2760 2765 Asp Gln Cys Ser Cys Cys Ser Pro Thr Arg Thr Glu Pro Met Gln Val 2770 2775 2780 Ala Leu His Cys Thr Asn Gly Ser Val Val Tyr His Glu Val Leu Asn 2785 2790 2795 2800 Ala Met Glu Cys Lys Cys Ser Pro Arg Lys Cys Ser Lys 2805 2810 <210> 75 <211> 219 <212> PRT <213> Homo sapiens <400> 75 Met Leu Asn Ile Ile Leu Ile Lys Phe Ser Ser Phe Ser Ile Arg Cys 1 5 10 15 Ala Ile Leu Ser Ser Val Cys Leu Asn Glu Ala Ile Thr Phe Ala Phe 20 25 30 Leu Leu Gln Val Phe Leu Trp Asn Met Asp Lys Tyr Thr Met Ile Arg 35 40 45 Lys Leu Glu Gly His His His Asp Val Val Ala Cys Asp Phe Ser Pro 50 55 60 Asp Gly Ala Leu Leu Ala Thr Ala Ser Tyr Asp Thr Arg Val Tyr Ile 65 70 75 80 Trp Asp Pro His Asn Gly Asp Ile Leu Met Glu Phe Gly His Leu Phe 85 90 95 Pro Pro Pro Thr Pro Ile Phe Ala Gly Gly Ala Asn Asp Arg Trp Val 100 105 110 Arg Ser Val Ser Phe Ser His Asp Gly Leu His Val Ala Ser Leu Ala 115 120 125 Asp Asp Lys Met Val Arg Phe Trp Arg Ile Asp Glu Asp Tyr Pro Val 130 135 140 Gln Val Ala Pro Leu Ser Asn Gly Leu Cys Cys Ala Phe Ser Thr Asp 145 150 155 160 Gly Ser Val Leu Ala Ala Gly Thr His Asp Gly Ser Val Tyr Phe Trp 165 170 175 Ala Thr Pro Arg Gln Val Pro Ser Leu Gln His Leu Cys Arg Met Ser 180 185 190 Ile Arg Arg Val Met Pro Thr Gln Glu Val Gln Glu Leu Pro Ile Pro 195 200 205 Ser Lys Leu Leu Glu Phe Leu Ser Tyr Arg Ile 210 215 <210> 76 <211> 95 <212> PRT <213> Homo sapiens <400> 76 Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Val Ser Gln Gly Ile Ser Ser Tyr 20 25 30 Leu Asn Trp Tyr Arg Gln Lys Pro Gly Lys Val Pro Lys Leu Leu Ile 35 40 45 Tyr Ser Ala Ser Asn Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Val Ala Thr Tyr Tyr Gly Gln Arg Thr Tyr Asn Ala Pro 85 90 95 <210> 77 <211> 239 <212> PRT <213> Homo sapiens <400> 77 Met Ala Trp Ile Pro Leu Leu Leu Pro Leu Leu Thr Leu Cys Thr Gly 1 5 10 15 Ser Trp Ala Gln Ser Ala Leu Ile Gln Pro Pro Ser Val Ser Gly Ser 20 25 30 Pro Gly Gln Ser Val Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val 35 40 45 Gly Ser Tyr Asp Tyr Val Ser Trp Tyr Gln Gln His Pro Gly Thr Val 50 55 60 Pro Lys Pro Met Ile Tyr Asn Val Asn Thr Gln Pro Ser Gly Val Pro 65 70 75 80 Asp Arg Phe Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Met Thr Ile 85 90 95 Ser Gly Leu Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Gln Arg 100 105 110 Ser Leu Ser Asp Ser Leu Ser Leu Cys Tyr Val Phe Gly Thr Gly Thr 115 120 125 Lys Val Thr Val Leu Gly Gln Pro Lys Ala Asn Pro Thr Val Thr Leu 130 135 140 Phe Pro Pro Ser Ser Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val 145 150 155 160 Cys Leu Ile Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys 165 170 175 Ala Asp Gly Ser Pro Val Lys Ala Gly Val Glu Thr Thr Lys Pro Ser 180 185 190 Lys Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr 195 200 205 Pro Glu Gln Trp Lys Ser His Arg Ser Tyr Ser Cys Gln Val Thr His 210 215 220 Glu Gly Ser Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 225 230 235 <210> 78 <211> 2544 <212> PRT <213> Homo sapiens <400> 78 Met Val Ala Leu Ser Leu Lys Ile Cys Val Arg His Cys Asn Val Val 1 5 10 15 Lys Thr Met Gln Phe Glu Pro Ser Thr Ala Val Tyr Asp Ala Cys Arg 20 25 30 Val Ile Arg Glu Arg Val Pro Glu Ala Gln Thr Gly Gln Ala Ser Asp 35 40 45 Tyr Gly Leu Phe Leu Ser Asp Glu Asp Pro Arg Lys Gly Ile Trp Leu 50 55 60 Glu Ala Gly Arg Thr Leu Asp Tyr Tyr Met Leu Arg Asn Gly Asp Ile 65 70 75 80 Leu Glu Tyr Lys Lys Lys Gln Arg Pro Gln Lys Ile Arg Met Leu Asp 85 90 95 Gly Ser Val Lys Thr Val Met Val Asp Asp Ser Lys Thr Val Gly Glu 100 105 110 Leu Leu Val Thr Ile Cys Ser Arg Ile Gly Ile Thr Asn Tyr Glu Glu 115 120 125 Tyr Ser Leu Ile Gln Glu Thr Ile Glu Glu Lys Lys Glu Glu Gly Thr 130 135 140 Gly Thr Leu Lys Lys Asp Arg Thr Leu Leu Arg Asp Glu Arg Lys Met 145 150 155 160 Glu Lys Leu Lys Ala Lys Leu His Thr Asp Asp Asp Leu Asn Trp Leu 165 170 175 Asp His Ser Arg Thr Phe Arg Glu Gln Gly Val Asp Glu Asn Glu Thr 180 185 190 Leu Leu Leu Arg Arg Lys Phe Phe Tyr Ser Asp Gln Asn Val Asp Ser 195 200 205 Arg Asp Pro Val Gln Leu Asn Leu Leu Tyr Val Gln Ala Arg Asp Asp 210 215 220 Ile Leu Asn Gly Ser His Pro Val Ser Phe Glu Lys Ala Cys Glu Phe 225 230 235 240 Gly Gly Phe Gln Ala Gln Ile Gln Phe Gly Pro His Val Glu His Lys 245 250 255 His Lys Pro Gly Phe Leu Asp Leu Lys Glu Phe Leu Pro Lys Glu Tyr 260 265 270 Ile Lys Gln Arg Gly Ala Glu Lys Arg Ile Phe Gln Glu His Lys Asn 275 280 285 Cys Gly Glu Met Ser Glu Ile Glu Ala Lys Val Lys Tyr Val Lys Leu 290 295 300 Ala Arg Ser Leu Arg Thr Tyr Gly Val Ser Phe Phe Leu Val Lys Glu 305 310 315 320 Lys Met Lys Gly Lys Asn Lys Leu Val Pro Arg Leu Leu Gly Ile Thr 325 330 335 Lys Asp Ser Val Met Arg Val Asp Glu Lys Thr Lys Glu Val Leu Gln 340 345 350 Glu Trp Pro Leu Thr Thr Val Lys Arg Trp Ala Ala Ser Pro Lys Ser 355 360 365 Phe Thr Leu Asp Phe Gly Glu Tyr Gln Glu Ser Tyr Tyr Ser Val Gln 370 375 380 Thr Thr Glu Gly Glu Gln Ile Ser Gln Leu Ile Ala Gly Tyr Ile Asp 385 390 395 400 Ile Ile Leu Lys Lys Lys Gln Ser Lys Asp Arg Phe Gly Leu Glu Gly 405 410 415 Asp Glu Glu Ser Thr Met Leu Glu Glu Ser Val Ser Pro Lys Lys Ser 420 425 430 Thr Ile Leu Gln Gln Gln Phe Asn Arg Thr Gly Lys Ala Glu His Gly 435 440 445 Ser Val Ala Leu Pro Ala Val Met Arg Ser Gly Ser Ser Gly Pro Glu 450 455 460 Thr Phe Asn Val Gly Ser Met Pro Ser Pro Gln Gln Gln Val Met Val 465 470 475 480 Gly Gln Met His Arg Gly His Met Pro Pro Leu Thr Ser Ala Gln Gln 485 490 495 Ala Leu Met Gly Thr Ile Asn Thr Ser Met His Ala Val Gln Gln Ala 500 505 510 Gln Asp Asp Leu Ser Glu Leu Asp Ser Leu Pro Pro Leu Gly Gln Asp 515 520 525 Met Ala Ser Arg Val Trp Val Gln Asn Lys Val Asp Glu Ser Lys His 530 535 540 Glu Ile His Ser Gln Val Asp Ala Ile Thr Ala Gly Thr Ala Ser Val 545 550 555 560 Val Asn Leu Thr Ala Gly Asp Pro Ala Asp Thr Asp Tyr Thr Ala Val 565 570 575 Gly Cys Ala Ile Thr Thr Ile Ser Ser Asn Leu Thr Glu Met Ser Lys 580 585 590 Gly Val Lys Leu Leu Ala Ala Leu Met Asp Asp Glu Val Gly Ser Gly 595 600 605 Glu Asp Leu Leu Arg Ala Ala Arg Thr Leu Ala Gly Ala Val Ser Asp 610 615 620 Leu Leu Lys Ala Val Gln Pro Thr Ser Gly Glu Pro Arg Gln Thr Val 625 630 635 640 Leu Thr Ala Ala Gly Ser Ile Gly Gln Ala Ser Gly Asp Leu Leu Arg 645 650 655 Gln Ile Gly Glu Asn Glu Thr Asp Glu Arg Phe Gln Asp Val Leu Met 660 665 670 Ser Leu Ala Lys Ala Val Ala Asn Ala Ala Ala Met Leu Val Leu Lys 675 680 685 Ala Lys Asn Val Ala Gln Val Ala Glu Asp Thr Val Leu Gln Asn Arg 690 695 700 Val Ile Ala Ala Ala Thr Gln Cys Ala Leu Ser Thr Ser Gln Leu Val 705 710 715 720 Ala Cys Ala Lys Val Val Ser Pro Thr Ile Ser Ser Pro Val Cys Gln 725 730 735 Glu Gln Leu Ile Glu Ala Gly Lys Leu Val Asp Arg Ser Val Glu Asn 740 745 750 Cys Val Arg Ala Cys Gln Ala Ala Thr Thr Asp Ser Glu Leu Leu Lys 755 760 765 Gln Val Ser Ala Ala Ala Ser Val Val Ser Gln Ala Leu His Asp Leu 770 775 780 Leu Gln His Val Arg Gln Phe Ala Ser Arg Gly Glu Pro Ile Gly Arg 785 790 795 800 Tyr Asp Gln Ala Thr Asp Thr Ile Met Cys Val Thr Glu Ser Ile Phe 805 810 815 Ser Ser Met Gly Asp Ala Gly Glu Met Val Arg Gln Ala Arg Val Leu 820 825 830 Ala Gln Ala Thr Ser Asp Leu Val Asn Ala Met Arg Ser Asp Ala Glu 835 840 845 Ala Glu Ile Asp Met Glu Asn Ser Lys Lys Leu Leu Ala Ala Ala Lys 850 855 860 Leu Leu Ala Asp Ser Thr Ala Arg Met Val Glu Ala Ala Lys Gly Ala 865 870 875 880 Ala Ala Asn Pro Glu Asn Glu Asp Gln Gln Gln Arg Leu Arg Glu Ala 885 890 895 Ala Glu Gly Leu Arg Val Ala Thr Asn Ala Ala Ala Gln Asn Ala Ile 900 905 910 Lys Lys Lys Ile Val Asn Arg Leu Glu Val Ala Ala Lys Gln Ala Ala 915 920 925 Ala Ala Ala Thr Gln Thr Ile Ala Ala Ser Gln Asn Ala Ala Val Ser 930 935 940 Asn Lys Asn Pro Ala Ala Gln Gln Gln Leu Val Gln Ser Cys Lys Ala 945 950 955 960 Val Ala Asp His Ile Pro Gln Leu Val Gln Gly Val Arg Gly Ser Gln 965 970 975 Ala Gln Ala Glu Asp Leu Ser Ala Gln Leu Ala Leu Ile Ile Ser Ser 980 985 990 Gln Asn Phe Leu Gln Pro Gly Ser Lys Met Val Ser Ser Ala Lys Ala 995 1000 1005 Ala Val Pro Thr Val Ser Asp Gln Ala Ala Ala Met Gln Leu Ser Gln 1010 1015 1020 Cys Ala Lys Asn Leu Ala Thr Ser Leu Ala Glu Leu Arg Thr Ala Ser 1025 1030 1035 1040 Gln Lys Ala Ile Ala His Glu Ala Cys Gly Pro Met Glu Ile Asp Ser 1045 1050 1055 Ala Leu Asn Thr Val Gln Thr Leu Lys Asn Glu Leu Gln Asp Ala Lys 1060 1065 1070 Met Ala Ala Val Glu Ser Gln Leu Lys Pro Leu Pro Gly Glu Thr Leu 1075 1080 1085 Glu Lys Cys Ala Gln Asp Leu Gly Ser Thr Ser Lys Ala Val Gly Ser 1090 1095 1100 Ser Met Ala Gln Leu Leu Thr Cys Ala Ala Gln Gly Asn Glu His Tyr 1105 1110 1115 1120 Thr Gly Val Ala Ala Arg Glu Thr Ala Gln Ala Leu Lys Thr Leu Ala 1125 1130 1135 Gln Ala Ala Arg Gly Val Ala Ala Ser Thr Thr Asp Pro Ala Ala Ala 1140 1145 1150 His Ala Met Leu Asp Ser Ala Arg Asp Val Met Glu Gly Ser Ala Met 1155 1160 1165 Leu Ile Gln Glu Ala Lys Gln Ala Leu Ile Ala Pro Gly Asp Ala Glu 1170 1175 1180 Arg Gln Gln Arg Leu Ala Gln Val Ala Lys Ala Val Ser His Ser Leu 1185 1190 1195 1200 Asn Asn Cys Val Asn Cys Leu Pro Gly Gln Lys Asp Val Asp Val Ala 1205 1210 1215 Leu Lys Ser Ile Gly Glu Ser Ser Lys Lys Leu Leu Val Asp Ser Leu 1220 1225 1230 Pro Pro Ser Thr Lys Pro Phe Gln Glu Ala Gln Ser Glu Leu Asn Gln 1235 1240 1245 Ala Ala Ala Asp Leu Asn Gln Ser Ala Gly Glu Val Val His Ala Thr 1250 1255 1260 Arg Gly Gln Ser Gly Glu Leu Ala Ala Ala Ser Gly Lys Phe Ser Asp 1265 1270 1275 1280 Asp Phe Asp Glu Phe Leu Asp Ala Gly Ile Glu Met Ala Gly Gln Ala 1285 1290 1295 Gln Thr Lys Glu Asp Gln Ile Gln Val Ile Gly Asn Leu Lys Asn Ile 1300 1305 1310 Ser Met Ala Ser Ser Lys Leu Leu Leu Ala Ala Lys Ser Leu Ser Val 1315 1320 1325 Asp Pro Gly Ala Pro Asn Ala Lys Asn Leu Leu Ala Ala Ala Ala Arg 1330 1335 1340 Ala Val Thr Glu Ser Ile Asn Gln Leu Ile Thr Leu Cys Thr Gln Gln 1345 1350 1355 1360 Ala Pro Gly Gln Lys Glu Cys Asp Asn Ala Leu Arg Glu Leu Glu Thr 1365 1370 1375 Val Lys Gly Met Leu Asp Asn Pro Asn Glu Pro Val Ser Asp Leu Ser 1380 1385 1390 Tyr Phe Asp Cys Ile Glu Ser Val Met Glu Asn Ser Lys Val Leu Gly 1395 1400 1405 Glu Ser Met Ala Gly Ile Ser Gln Asn Ala Lys Thr Gly Asp Leu Pro 1410 1415 1420 Ala Phe Gly Glu Cys Val Gly Ile Ala Ser Lys Ala Leu Cys Gly Leu 1425 1430 1435 1440 Thr Glu Ala Ala Ala Gln Ala Ala Tyr Leu Val Gly Ile Ser Asp Pro 1445 1450 1455 Asn Ser Gln Ala Gly His Gln Gly Leu Val Asp Pro Ile Gln Phe Ala 1460 1465 1470 Arg Ala Asn Gln Ala Ile Gln Met Ala Cys Gln Asn Leu Val Asp Pro 1475 1480 1485 Gly Ser Ser Pro Ser Gln Val Leu Ser Ala Ala Thr Ile Val Ala Lys 1490 1495 1500 His Thr Ser Ala Leu Cys Asn Ala Cys Arg Ile Ala Ser Ser Lys Thr 1505 1510 1515 1520 Ala Asn Pro Val Ala Lys Arg His Phe Val Gln Ser Ala Lys Glu Val 1525 1530 1535 Ala Asn Ser Thr Ala Asn Leu Val Lys Thr Ile Lys Ala Leu Asp Gly 1540 1545 1550 Asp Phe Ser Glu Asp Asn Arg Asn Lys Cys Arg Ile Ala Thr Ala Pro 1555 1560 1565 Leu Ile Glu Ala Val Glu Asn Leu Thr Ala Phe Ala Ser Asn Pro Glu 1570 1575 1580 Phe Val Ser Ile Pro Ala Gln Ile Ser Ser Glu Gly Ser Gln Ala Gln 1585 1590 1595 1600 Glu Pro Ile Leu Val Ser Ala Lys Thr Met Leu Glu Ser Ser Ser Tyr 1605 1610 1615 Leu Ile Arg Thr Ala Arg Ser Leu Ala Ile Asn Pro Lys Asp Pro Pro 1620 1625 1630 Thr Trp Ser Val Leu Ala Gly His Ser His Thr Val Ser Asp Ser Ile 1635 1640 1645 Lys Ser Leu Ile Thr Ser Ile Arg Asp Lys Ala Pro Gly Gln Arg Glu 1650 1655 1660 Cys Asp Tyr Ser Ile Asp Gly Ile Asn Arg Cys Ile Arg Asp Ile Glu 1665 1670 1675 1680 Gln Ala Ser Leu Ala Ala Val Ser Gln Ser Leu Ala Thr Arg Asp Asp 1685 1690 1695 Ile Ser Val Glu Ala Leu Gln Glu Gln Leu Thr Ser Val Val Gln Glu 1700 1705 1710 Ile Gly His Leu Ile Asp Pro Ile Ala Thr Ala Ala Arg Gly Glu Ala 1715 1720 1725 Ala Gln Leu Gly His Lys Val Thr Gln Leu Ala Ser Tyr Phe Glu Pro 1730 1735 1740 Leu Ile Leu Ala Ala Val Gly Val Ala Ser Lys Ile Leu Asp His Gln 1745 1750 1755 1760 Gln Gln Met Thr Val Leu Asp Gln Thr Lys Thr Leu Ala Glu Ser Ala 1765 1770 1775 Leu Gln Met Leu Tyr Ala Ala Lys Glu Gly Gly Gly Asn Pro Lys Ala 1780 1785 1790 Gln His Thr His Asp Ala Ile Thr Glu Ala Ala Gln Leu Met Lys Glu 1795 1800 1805 Ala Val Asp Asp Ile Met Val Thr Leu Asn Glu Ala Ala Ser Glu Val 1810 1815 1820 Gly Leu Val Gly Gly Met Val Asp Ala Ile Ala Glu Ala Met Ser Lys 1825 1830 1835 1840 Leu Asp Glu Gly Thr Pro Pro Glu Pro Lys Gly Thr Phe Val Asp Tyr 1845 1850 1855 Gln Thr Thr Val Val Lys Tyr Ser Lys Ala Ile Ala Val Thr Ala Gln 1860 1865 1870 Glu Met Met Thr Lys Ser Val Thr Asn Pro Glu Glu Leu Gly Gly Leu 1875 1880 1885 Ala Ser Gln Met Thr Ser Asp Tyr Gly His Leu Ala Phe Gln Gly Gln 1890 1895 1900 Met Ala Ala Ala Thr Ala Glu Pro Glu Glu Ile Gly Phe Gln Ile Arg 1905 1910 1915 1920 Thr Arg Val Gln Asp Leu Gly His Gly Cys Ile Phe Leu Val Gln Lys 1925 1930 1935 Ala Gly Ala Leu Gln Val Cys Pro Thr Asp Ser Tyr Thr Lys Arg Glu 1940 1945 1950 Leu Ile Glu Cys Ala Arg Ala Val Thr Glu Lys Val Ser Leu Val Leu 1955 1960 1965 Ser Ala Leu Gln Ala Gly Asn Lys Gly Thr Gln Ala Cys Ile Thr Ala 1970 1975 1980 Ala Thr Ala Val Ser Gly Ile Ile Ala Asp Leu Asp Thr Thr Ile Met 1985 1990 1995 2000 Phe Ala Thr Ala Gly Thr Leu Asn Ala Glu Asn Ser Glu Thr Phe Ala 2005 2010 2015 Asp His Arg Glu Asn Ile Leu Lys Thr Ala Lys Ala Leu Val Glu Asp 2020 2025 2030 Thr Lys Leu Leu Val Ser Gly Ala Ala Ser Thr Pro Asp Lys Leu Ala 2035 2040 2045 Gln Ala Ala Gln Ser Ser Ala Ala Thr Ile Thr Gln Leu Ala Glu Val 2050 2055 2060 Val Lys Leu Gly Ala Ala Ser Leu Gly Ser Asp Asp Pro Glu Thr Gln 2065 2070 2075 2080 Val Val Leu Ile Asn Ala Ile Lys Asp Val Ala Lys Ala Leu Ser Asp 2085 2090 2095 Leu Ile Ser Ala Thr Lys Gly Ala Ala Ser Lys Pro Val Asp Asp Pro 2100 2105 2110 Ser Met Tyr Gln Leu Lys Gly Ala Ala Lys Val Met Val Thr Asn Val 2115 2120 2125 Thr Ser Leu Leu Lys Thr Val Lys Ala Val Glu Asp Glu Ala Thr Arg 2130 2135 2140 Gly Thr Arg Ala Leu Glu Ala Thr Ile Glu Cys Ile Lys Gln Glu Leu 2145 2150 2155 2160 Thr Val Phe Gln Ser Lys Asp Val Pro Glu Lys Thr Ser Ser Pro Glu 2165 2170 2175 Glu Ser Ile Arg Met Thr Lys Gly Ile Thr Met Ala Thr Ala Lys Ala 2180 2185 2190 Val Ala Ala Gly Asn Ser Cys Arg Gln Glu Asp Val Ile Ala Thr Ala 2195 2200 2205 Asn Leu Ser Arg Lys Ala Val Ser Asp Met Leu Thr Ala Cys Lys Gln 2210 2215 2220 Ala Ser Phe His Pro Asp Val Ser Asp Glu Val Arg Thr Arg Ala Leu 2225 2230 2235 2240 Arg Phe Gly Thr Glu Cys Thr Leu Gly Tyr Leu Asp Leu Leu Glu His 2245 2250 2255 Val Leu Val Ile Leu Gln Lys Pro Thr Pro Glu Phe Lys Gln Gln Leu 2260 2265 2270 Ala Ala Phe Ser Lys Arg Val Ala Gly Ala Val Thr Glu Leu Ile Gln 2275 2280 2285 Ala Ala Glu Ala Met Lys Gly Thr Glu Trp Val Asp Pro Glu Asp Pro 2290 2295 2300 Thr Val Ile Ala Glu Thr Glu Leu Leu Gly Ala Ala Ala Ser Ile Glu 2305 2310 2315 2320 Ala Ala Ala Lys Lys Leu Glu Gln Leu Lys Pro Arg Ala Lys Pro Lys 2325 2330 2335 Gln Ala Asp Glu Thr Leu Asp Phe Glu Glu Gln Ile Leu Glu Ala Ala 2340 2345 2350 Lys Ser Ile Ala Ala Ala Thr Ser Ala Leu Val Lys Ser Ala Ser Ala 2355 2360 2365 Ala Gln Arg Glu Leu Val Ala Gln Gly Lys Val Gly Ser Ile Pro Ala 2370 2375 2380 Asn Ala Ala Asp Asp Gly Gln Trp Ser Gln Gly Leu Ile Ser Ala Ala 2385 2390 2395 2400 Arg Met Val Ala Ala Ala Thr Ser Ser Leu Cys Glu Ala Ala Asn Ala 2405 2410 2415 Ser Val Gln Gly His Ala Ser Glu Glu Lys Leu Ile Ser Ser Ala Lys 2420 2425 2430 Gln Val Ala Ala Ser Thr Ala Gln Leu Leu Val Ala Cys Lys Val Lys 2435 2440 2445 Ala Asp Gln Asp Ser Glu Ala Met Arg Arg Leu Gln Ala Ala Gly Asn 2450 2455 2460 Ala Val Lys Arg Ala Ser Asp Asn Leu Val Arg Ala Ala Gln Lys Ala 2465 2470 2475 2480 Ala Phe Gly Lys Ala Asp Asp Asp Asp Val Val Val Lys Thr Lys Phe 2485 2490 2495 Val Gly Gly Ile Ala Gln Ile Ile Ala Ala Gln Glu Glu Met Leu Lys 2500 2505 2510 Lys Glu Arg Glu Leu Glu Glu Ala Arg Lys Lys Leu Ala Gln Ile Arg 2515 2520 2525 Gln Gln Gln Tyr Lys Phe Leu Pro Thr Glu Leu Arg Glu Asp Glu Gly 2530 2535 2540 <210> 79 <211> 3013 <212> PRT <213> Homo sapiens <400> 79 Met Glu Glu Lys Gln Gln Ile Ile Leu Ala Asn Gln Asp Gly Gly Thr 1 5 10 15 Val Ala Gly Ala Ala Pro Thr Phe Phe Val Ile Leu Lys Gln Pro Gly 20 25 30 Asn Gly Lys Thr Asp Gln Gly Ile Leu Val Thr Asn Gln Asp Ala Cys 35 40 45 Ala Leu Ala Ser Ser Val Ser Ser Pro Val Lys Ser Lys Gly Lys Ile 50 55 60 Cys Leu Pro Ala Asp Cys Thr Val Gly Gly Ile Thr Val Thr Leu Asp 65 70 75 80 Asn Asn Ser Met Trp Asn Glu Phe Tyr His Arg Ser Thr Glu Met Ile 85 90 95 Leu Thr Lys Gln Gly Arg Arg Met Phe Pro Tyr Cys Arg Tyr Trp Ile 100 105 110 Thr Gly Leu Asp Ser Asn Leu Lys Tyr Ile Leu Val Met Asp Ile Ser 115 120 125 Pro Val Asp Asn His Arg Tyr Lys Trp Asn Gly Arg Trp Trp Glu Pro 130 135 140 Ser Gly Lys Ala Glu Pro His Val Leu Gly Arg Val Phe Ile His Pro 145 150 155 160 Glu Ser Pro Ser Thr Gly His Tyr Trp Met His Gln Pro Val Ser Phe 165 170 175 Tyr Lys Leu Lys Leu Thr Asn Asn Thr Leu Asp Gln Glu Gly His Ile 180 185 190 Ile Leu His Ser Met His Arg Tyr Leu Pro Arg Leu His Leu Val Pro 195 200 205 Ala Glu Lys Ala Val Glu Val Ile Gln Leu Asn Gly Pro Gly Val His 210 215 220 Thr Phe Thr Phe Pro Gln Thr Glu Phe Phe Ala Val Thr Ala Tyr Gln 225 230 235 240 Asn Ile Gln Ile Thr Gln Leu Lys Ile Asp Tyr Asn Pro Phe Ala Lys 245 250 255 Gly Phe Arg Asp Asp Gly Leu Asn Asn Lys Pro Gln Arg Asp Gly Lys 260 265 270 Gln Lys Asn Ser Ser Asp Gln Glu Gly Asn Asn Ile Ser Ser Ser Ser 275 280 285 Gly His Arg Val Arg Leu Thr Glu Gly Gln Gly Ser Glu Ile Gln Pro 290 295 300 Gly Asp Leu Asp Pro Leu Ser Arg Gly His Glu Thr Ser Gly Lys Gly 305 310 315 320 Leu Glu Lys Thr Ser Leu Asn Ile Lys Arg Asp Phe Leu Gly Phe Met 325 330 335 Asp Thr Asp Ser Ala Leu Ser Glu Val Pro Gln Leu Lys Gln Glu Ile 340 345 350 Ser Glu Cys Leu Ile Ala Ser Ser Phe Glu Asp Asp Ser Arg Val Ala 355 360 365 Ser Pro Leu Asp Gln Asn Gly Ser Phe Asn Val Val Ile Lys Glu Glu 370 375 380 Pro Leu Asp Asp Tyr Asp Tyr Glu Leu Gly Glu Cys Pro Glu Gly Val 385 390 395 400 Thr Val Lys Gln Glu Glu Thr Asp Glu Glu Thr Asp Val Tyr Ser Asn 405 410 415 Ser Asp Asp Asp Pro Ile Leu Glu Lys Gln Leu Lys Arg His Asn Lys 420 425 430 Val Asp Asn Pro Glu Ala Asp His Leu Ser Ser Lys Trp Leu Pro Ser 435 440 445 Ser Pro Ser Gly Val Ala Lys Ala Lys Met Phe Lys Leu Asp Thr Gly 450 455 460 Lys Met Pro Val Val Tyr Leu Glu Pro Cys Ala Val Thr Arg Ser Thr 465 470 475 480 Val Lys Ile Ser Glu Leu Pro Asp Asn Met Leu Ser Thr Ser Arg Lys 485 490 495 Asp Lys Ser Ser Met Leu Ala Glu Leu Glu Tyr Leu Pro Thr Tyr Ile 500 505 510 Glu Asn Ser Asn Glu Thr Ala Phe Cys Leu Gly Lys Glu Ser Glu Asn 515 520 525 Gly Leu Arg Lys His Ser Pro Asp Leu Arg Val Val Gln Lys Tyr Pro 530 535 540 Leu Leu Lys Glu Pro Gln Trp Lys Tyr Pro Asp Ile Ser Asp Ser Ile 545 550 555 560 Ser Thr Glu Arg Ile Leu Asp Asp Ser Lys Asp Ser Val Gly Asp Ser 565 570 575 Leu Ser Gly Lys Glu Asp Leu Gly Arg Lys Arg Thr Thr Met Leu Lys 580 585 590 Ile Ala Thr Ala Ala Lys Val Val Asn Ala Asn Gln Asn Ala Ser Pro 595 600 605 Asn Val Pro Gly Lys Arg Gly Arg Pro Arg Lys Leu Lys Leu Cys Lys 610 615 620 Ala Gly Arg Pro Pro Lys Asn Thr Gly Lys Ser Leu Ile Ser Thr Lys 625 630 635 640 Asn Thr Pro Val Ser Pro Gly Ser Thr Phe Pro Asp Val Lys Pro Asp 645 650 655 Leu Glu Asp Val Asp Gly Val Leu Phe Val Ser Phe Glu Ser Lys Glu 660 665 670 Ala Leu Asp Ile His Ala Val Asp Gly Thr Thr Glu Glu Ser Ser Ser 675 680 685 Leu Gln Ala Ser Thr Thr Asn Asp Ser Gly Tyr Arg Ala Arg Ile Ser 690 695 700 Gln Leu Glu Lys Glu Leu Ile Glu Asp Leu Lys Thr Leu Arg His Lys 705 710 715 720 Gln Val Ile His Pro Gly Leu Gln Glu Val Gly Leu Lys Leu Asn Ser 725 730 735 Val Asp Pro Thr Met Ser Ile Asp Leu Lys Tyr Leu Gly Val Gln Leu 740 745 750 Pro Leu Ala Pro Ala Thr Ser Phe Pro Phe Trp Asn Leu Thr Gly Thr 755 760 765 Asn Pro Ala Ser Pro Asp Ala Gly Phe Pro Phe Val Ser Arg Thr Gly 770 775 780 Lys Thr Asn Asp Phe Thr Lys Ile Lys Gly Trp Arg Gly Lys Phe His 785 790 795 800 Ser Ala Ser Ala Ser Arg Asn Glu Gly Gly Asn Ser Glu Ser Ser Leu 805 810 815 Lys Asn Arg Ser Ala Phe Cys Ser Asp Lys Leu Asp Glu Tyr Leu Glu 820 825 830 Asn Glu Gly Lys Leu Met Glu Thr Ser Met Gly Phe Ser Ser Asn Ala 835 840 845 Pro Thr Ser Pro Val Val Tyr Gln Leu Pro Thr Lys Ser Thr Ser Tyr 850 855 860 Val Arg Thr Leu Asp Ser Val Leu Lys Lys Gln Ser Thr Ile Ser Pro 865 870 875 880 Ser Thr Ser Tyr Ser Leu Lys Pro His Ser Val Pro Pro Val Ser Arg 885 890 895 Lys Ala Lys Ser Gln Asn Arg Gln Ala Thr Phe Ser Gly Arg Thr Lys 900 905 910 Ser Ser Tyr Lys Ser Ile Leu Pro Tyr Pro Val Ser Pro Lys Gln Lys 915 920 925 Tyr Ser His Val Ile Leu Gly Asp Lys Val Thr Lys Asn Ser Ser Gly 930 935 940 Ile Ile Ser Glu Asn Gln Ala Asn Asn Phe Val Val Pro Thr Leu Asp 945 950 955 960 Glu Asn Ile Phe Pro Lys Gln Ile Ser Leu Arg Gln Ala Gln Gln Gln 965 970 975 Gln Gln Gln Gln Gln Gly Ser Arg Pro Pro Gly Leu Ser Lys Ser Gln 980 985 990 Val Lys Leu Met Asp Leu Glu Asp Cys Ala Leu Trp Glu Gly Lys Pro 995 1000 1005 Arg Thr Tyr Ile Thr Glu Glu Arg Ala Asp Val Ser Leu Thr Thr Leu 1010 1015 1020 Leu Thr Ala Gln Ala Ser Leu Lys Thr Lys Pro Ile His Thr Ile Ile 1025 1030 1035 1040 Arg Lys Arg Ala Pro Pro Cys Asn Asn Asp Phe Cys Arg Leu Gly Cys 1045 1050 1055 Val Cys Ser Ser Leu Ala Leu Glu Lys Arg Gln Pro Ala His Cys Arg 1060 1065 1070 Arg Pro Asp Cys Met Phe Gly Cys Thr Cys Leu Lys Arg Lys Val Val 1075 1080 1085 Leu Val Lys Gly Gly Ser Lys Thr Lys His Phe Gln Arg Lys Ala Ala 1090 1095 1100 His Arg Asp Pro Val Phe Tyr Asp Thr Leu Gly Glu Glu Ala Arg Glu 1105 1110 1115 1120 Glu Glu Glu Gly Ile Arg Glu Glu Glu Glu Gln Leu Lys Glu Lys Lys 1125 1130 1135 Lys Arg Lys Lys Leu Glu Tyr Thr Ile Cys Glu Thr Glu Pro Glu Gln 1140 1145 1150 Pro Val Arg His Tyr Pro Leu Trp Val Lys Val Glu Gly Glu Val Asp 1155 1160 1165 Pro Glu Pro Val Tyr Ile Pro Thr Pro Ser Val Ile Glu Pro Met Lys 1170 1175 1180 Pro Leu Leu Leu Pro Gln Pro Glu Val Leu Ser Pro Thr Val Lys Gly 1185 1190 1195 1200 Lys Leu Leu Thr Gly Ile Lys Ser Pro Arg Ser Tyr Thr Pro Lys Pro 1205 1210 1215 Asn Pro Val Ile Arg Glu Glu Asp Lys Asp Pro Val Tyr Leu Tyr Phe 1220 1225 1230 Glu Ser Met Met Thr Cys Ala Arg Val Arg Val Tyr Glu Arg Lys Lys 1235 1240 1245 Glu Asp Gln Arg Gln Pro Ser Ser Ser Ser Ser Pro Ser Pro Ser Phe 1250 1255 1260 Gln Gln Gln Thr Ser Cys His Ser Ser Pro Glu Asn His Asn Asn Ala 1265 1270 1275 1280 Lys Glu Pro Asp Ser Glu Gln Gln Pro Leu Lys Gln Leu Thr Cys Asp 1285 1290 1295 Leu Glu Asp Asp Ser Asp Lys Leu Gln Glu Lys Ser Trp Lys Ser Ser 1300 1305 1310 Cys Asn Glu Gly Glu Ser Ser Ser Thr Ser Tyr Met His Gln Arg Ser 1315 1320 1325 Pro Gly Gly Pro Thr Lys Leu Ile Glu Ile Ile Ser Asp Cys Asn Trp 1330 1335 1340 Glu Glu Asp Arg Asn Lys Ile Leu Ser Ile Leu Ser Gln His Ile Asn 1345 1350 1355 1360 Ser Asn Met Pro Gln Ser Leu Lys Val Gly Ser Phe Ile Ile Glu Leu 1365 1370 1375 Ala Ser Gln Arg Lys Ser Arg Gly Glu Lys Asn Pro Pro Val Tyr Ser 1380 1385 1390 Ser Arg Val Lys Ile Ser Met Pro Ser Cys Gln Asp Gln Asp Asp Met 1395 1400 1405 Ala Glu Lys Ser Gly Ser Glu Thr Pro Asp Gly Pro Leu Ser Pro Gly 1410 1415 1420 Lys Met Glu Asp Ile Ser Pro Val Gln Thr Asp Ala Leu Asp Ser Val 1425 1430 1435 1440 Arg Glu Arg Leu His Gly Gly Lys Gly Leu Pro Phe Tyr Ala Gly Leu 1445 1450 1455 Ser Pro Ala Gly Lys Leu Val Ala Tyr Lys Arg Lys Pro Ser Ser Ser 1460 1465 1470 Thr Ser Gly Leu Ile Gln Val Ala Ser Asn Ala Lys Val Ala Ala Ser 1475 1480 1485 Arg Lys Pro Arg Thr Leu Leu Pro Ser Thr Ser Asn Ser Lys Met Ala 1490 1495 1500 Ser Ser Ser Gly Thr Ala Thr Asn Arg Pro Gly Lys Asn Leu Lys Ala 1505 1510 1515 1520 Phe Val Pro Ala Lys Arg Pro Ile Ala Ala Arg Pro Ser Pro Gly Gly 1525 1530 1535 Val Phe Thr Gln Phe Val Met Ser Lys Val Gly Ala Leu Gln Gln Lys 1540 1545 1550 Ile Pro Gly Val Ser Thr Pro Gln Thr Leu Ala Gly Thr Gln Lys Phe 1555 1560 1565 Ser Ile Arg Pro Ser Pro Val Met Val Val Thr Pro Val Val Ser Ser 1570 1575 1580 Glu Pro Val Gln Val Cys Ser Pro Val Thr Ala Ala Val Thr Thr Thr 1585 1590 1595 1600 Thr Pro Gln Val Phe Leu Glu Asn Thr Thr Ala Val Thr Pro Met Thr 1605 1610 1615 Ala Ile Ser Asp Val Glu Thr Lys Glu Thr Thr Tyr Ser Ser Gly Ala 1620 1625 1630 Thr Thr Thr Gly Val Val Glu Val Ser Glu Thr Asn Thr Ser Thr Ser 1635 1640 1645 Val Thr Ser Thr Gln Ser Thr Ala Thr Val Asn Leu Thr Lys Thr Thr 1650 1655 1660 Gly Ile Thr Thr Pro Val Ala Ser Val Ala Phe Pro Lys Ser Leu Val 1665 1670 1675 1680 Ala Ser Pro Ser Thr Ile Thr Leu Pro Val Ala Ser Thr Ala Ser Thr 1685 1690 1695 Ser Leu Val Val Val Thr Ala Ala Ala Ser Ser Ser Met Val Thr Thr 1700 1705 1710 Pro Thr Ser Ser Leu Gly Ser Val Pro Ile Ile Leu Ser Gly Ile Asn 1715 1720 1725 Gly Ser Pro Pro Val Ser Gln Arg Pro Glu Asn Ala Ala Gln Ile Pro 1730 1735 1740 Val Ala Thr Pro Gln Val Ser Pro Asn Thr Val Lys Arg Ala Gly Pro 1745 1750 1755 1760 Arg Leu Leu His Pro Asn Gly Gln Ile Val Gln Leu Leu Pro Leu His 1765 1770 1775 Gln Leu Arg Gly Ser Asn Thr Gln Pro Asn Leu Gln Pro Val Met Phe 1780 1785 1790 Arg Asn Pro Gly Ser Val Met Gly Ile Arg Leu Pro Ala Pro Ser Lys 1795 1800 1805 Pro Ser Glu Thr Pro Pro Ser Ser Thr Ser Ser Ser Ala Phe Ser Val 1810 1815 1820 Met Asn Pro Val Ile Gln Ala Val Gly Ser Ser Ser Ala Val Asn Val 1825 1830 1835 1840 Ile Thr Gln Ala Pro Ser Leu Leu Ser Ser Gly Ala Ser Phe Val Ser 1845 1850 1855 Gln Ala Gly Thr Leu Thr Leu Arg Ile Ser Pro Pro Glu Pro Gln Ser 1860 1865 1870 Phe Ala Ser Lys Thr Gly Ser Glu Thr Lys Ile Thr Tyr Ser Ser Gly 1875 1880 1885 Gly Gln Pro Val Gly Thr Ala Ser Leu Ile Pro Leu Gln Ser Gly Ser 1890 1895 1900 Phe Ala Leu Leu Gln Leu Pro Gly Gln Lys Pro Val Pro Ser Ser Ile 1905 1910 1915 1920 Leu Gln His Val Ala Ser Leu Gln Met Lys Arg Glu Ser Gln Asn Pro 1925 1930 1935 Asp Gln Lys Asp Glu Thr Asn Ser Ile Lys Arg Glu Gln Glu Thr Lys 1940 1945 1950 Lys Val Leu Gln Ser Glu Gly Glu Ala Val Asp Pro Glu Ala Asn Val 1955 1960 1965 Ile Lys Gln Asn Ser Gly Ala Ala Thr Ser Glu Glu Thr Leu Asn Asp 1970 1975 1980 Ser Leu Glu Asp Arg Gly Asp His Leu Asp Glu Glu Cys Leu Pro Glu 1985 1990 1995 2000 Glu Gly Cys Ala Thr Val Lys Pro Ser Glu His Ser Cys Ile Thr Gly 2005 2010 2015 Ser His Thr Asp Gln Asp Tyr Lys Asp Val Asn Glu Glu Tyr Gly Ala 2020 2025 2030 Arg Asn Arg Lys Ser Ser Lys Glu Lys Val Ala Val Leu Glu Val Arg 2035 2040 2045 Thr Ile Lys Val Gln His Gln Lys Leu Gly Asp Val Lys Val Glu Gln 2050 2055 2060 Gln Lys Gly Phe Asp Asn Pro Glu Glu Asn Ser Ser Glu Phe Pro Val 2065 2070 2075 2080 Thr Phe Lys Glu Glu Ser Lys Phe Glu Leu Ser Gly Ser Lys Val Met 2085 2090 2095 Glu Gln Gln Ser Asn Leu Gln Pro Glu Ala Lys Glu Lys Glu Cys Gly 2100 2105 2110 Asp Ser Leu Glu Lys Asp Arg Glu Arg Trp Arg Lys His Leu Lys Gly 2115 2120 2125 Pro Leu Thr Arg Lys Cys Val Gly Ala Ser Gln Glu Cys Lys Lys Glu 2130 2135 2140 Ala Asp Glu Gln Leu Ile Lys Glu Thr Lys Thr Cys Gln Glu Asn Ser 2145 2150 2155 2160 Asp Val Phe Gln Gln Glu Gln Gly Ile Ser Asp Leu Leu Gly Lys Ser 2165 2170 2175 Gly Ile Thr Glu Asp Ala Arg Val Leu Lys Thr Glu Cys Asp Ser Trp 2180 2185 2190 Ser Arg Ile Ser Asn Pro Ser Ala Phe Ser Ile Val Pro Arg Arg Ala 2195 2200 2205 Ala Lys Ser Ser Arg Gly Asn Gly His Phe Gln Gly His Leu Leu Leu 2210 2215 2220 Pro Gly Glu Gln Ile Gln Pro Lys Gln Glu Lys Lys Gly Gly Arg Ser 2225 2230 2235 2240 Ser Ala Asp Phe Thr Val Leu Asp Leu Glu Glu Asp Asp Glu Asp Asp 2245 2250 2255 Asn Glu Lys Thr Asp Asp Ser Ile Asp Glu Ile Val Asp Val Val Ser 2260 2265 2270 Asp Tyr Gln Ser Glu Glu Val Asp Asp Val Glu Lys Asn Asn Cys Val 2275 2280 2285 Glu Tyr Ile Glu Asp Asp Glu Glu His Val Asp Ile Glu Thr Val Glu 2290 2295 2300 Glu Leu Ser Glu Glu Ile Asn Val Ala His Leu Lys Thr Thr Ala Ala 2305 2310 2315 2320 His Thr Gln Ser Phe Lys Gln Pro Ser Cys Thr His Ile Ser Ala Asp 2325 2330 2335 Glu Lys Ala Ala Glu Arg Ser Arg Lys Ala Pro Pro Ile Pro Leu Lys 2340 2345 2350 Leu Lys Pro Asp Tyr Trp Ser Asp Lys Leu Gln Lys Glu Ala Glu Ala 2355 2360 2365 Phe Ala Tyr Tyr Arg Arg Thr His Thr Ala Asn Glu Arg Arg Arg Arg 2370 2375 2380 Gly Glu Met Arg Asp Leu Phe Glu Lys Leu Lys Ile Thr Leu Gly Leu 2385 2390 2395 2400 Leu His Ser Ser Lys Val Ser Lys Ser Leu Ile Leu Thr Arg Ala Phe 2405 2410 2415 Ser Glu Ile Gln Gly Leu Thr Asp Gln Ala Asp Lys Leu Ile Gly Gln 2420 2425 2430 Lys Asn Leu Leu Thr Arg Lys Arg Asn Ile Leu Ile Arg Lys Val Ser 2435 2440 2445 Ser Leu Ser Gly Lys Thr Glu Glu Val Val Leu Lys Lys Leu Glu Tyr 2450 2455 2460 Ile Tyr Ala Lys Gln Gln Ala Leu Glu Ala Gln Lys Arg Lys Lys Lys 2465 2470 2475 2480 Met Gly Ser Asp Glu Phe Asp Ile Ser Pro Arg Ile Ser Lys Gln Gln 2485 2490 2495 Glu Gly Ser Ser Ala Ser Ser Val Asp Leu Gly Gln Met Phe Ile Asn 2500 2505 2510 Asn Arg Arg Gly Lys Pro Leu Ile Leu Ser Arg Lys Lys Asp Gln Ala 2515 2520 2525 Thr Glu Asn Thr Ser Pro Leu Asn Thr Pro His Thr Ser Ala Asn Leu 2530 2535 2540 Val Met Thr Pro Gln Gly Gln Leu Leu Thr Leu Lys Gly Pro Leu Phe 2545 2550 2555 2560 Ser Gly Pro Val Val Ala Val Ser Pro Asp Leu Leu Glu Ser Asp Leu 2565 2570 2575 Lys Pro Gln Val Ala Gly Ser Ala Val Ala Leu Pro Glu Asn Asp Asp 2580 2585 2590 Leu Phe Met Met Pro Arg Ile Val Asn Val Thr Ser Leu Ala Thr Glu 2595 2600 2605 Gly Gly Leu Val Asp Met Gly Gly Ser Lys Tyr Pro His Glu Val Pro 2610 2615 2620 Asp Ser Lys Pro Ser Asp His Leu Lys Asp Thr Val Arg Asn Glu Asp 2625 2630 2635 2640 Asn Ser Leu Glu Asp Lys Gly Arg Ile Ser Ser Arg Gly Asn Arg Asp 2645 2650 2655 Gly Arg Val Thr Leu Gly Pro Thr Gln Val Phe Leu Ala Asn Lys Asp 2660 2665 2670 Ser Gly Tyr Pro Gln Ile Val Asp Val Ser Asn Met Gln Lys Ala Gln 2675 2680 2685 Glu Phe Leu Pro Lys Lys Ile Ser Gly Asp Met Arg Gly Ile Gln Tyr 2690 2695 2700 Lys Trp Lys Glu Ser Glu Ser Arg Gly Glu Arg Val Lys Ser Lys Asp 2705 2710 2715 2720 Ser Ser Phe His Lys Leu Lys Met Lys Asp Leu Lys Asp Ser Ser Ile 2725 2730 2735 Glu Met Glu Leu Arg Lys Val Thr Ser Ala Ile Glu Glu Ala Ala Leu 2740 2745 2750 Asp Ser Ser Glu Leu Leu Thr Asn Met Glu Asp Glu Asp Asp Thr Asp 2755 2760 2765 Glu Thr Leu Thr Ser Leu Leu Asn Glu Ile Ala Phe Leu Asn Gln Gln 2770 2775 2780 Leu Asn Asp Asp Ser Val Gly Leu Ala Glu Leu Pro Ser Ser Met Asp 2785 2790 2795 2800 Thr Glu Phe Pro Gly Asp Ala Arg Arg Ala Phe Ile Ser Lys Val Pro 2805 2810 2815 Pro Gly Ser Arg Ala Thr Phe Gln Val Glu His Leu Gly Thr Gly Leu 2820 2825 2830 Lys Glu Leu Pro Asp Val Gln Gly Glu Ser Asp Ser Ile Ser Pro Leu 2835 2840 2845 Leu Leu His Leu Glu Asp Asp Asp Phe Ser Glu Asn Glu Lys Gln Leu 2850 2855 2860 Ala Glu Pro Ala Ser Glu Pro Asp Val Leu Lys Ile Val Ile Asp Ser 2865 2870 2875 2880 Glu Ile Lys Asp Ser Leu Leu Ser Asn Lys Lys Ala Ile Asp Gly Gly 2885 2890 2895 Lys Asn Thr Ser Gly Leu Pro Ala Glu Pro Glu Ser Val Ser Ser Pro 2900 2905 2910 Pro Thr Leu His Met Lys Thr Gly Leu Glu Asn Ser Asn Ser Thr Asp 2915 2920 2925 Thr Leu Trp Arg Pro Met Pro Lys Leu Ala Pro Leu Gly Leu Lys Val 2930 2935 2940 Ala Asn Pro Ser Ser Asp Ala Asp Gly Gln Ser Leu Lys Val Met Pro 2945 2950 2955 2960 Cys Leu Ala Pro Ile Ala Ala Lys Val Gly Ser Val Gly His Lys Met 2965 2970 2975 Asn Leu Thr Gly Asn Asp Gln Glu Gly Arg Glu Ser Lys Val Met Pro 2980 2985 2990 Thr Leu Ala Pro Val Val Ala Lys Leu Gly Asn Ser Gly Ala Ser Pro 2995 3000 3005 Ser Ser Ala Gly Lys 3010 <210> 80 <211> 195 <212> PRT <213> Homo sapiens <400> 80 Met Ala Pro Pro Val Arg Tyr Cys Ile Pro Gly Glu Arg Leu Cys Asn 1 5 10 15 Leu Glu Glu Gly Ser Pro Gly Ser Gly Thr Tyr Thr Arg His Gly Tyr 20 25 30 Ile Phe Ser Ser Leu Ala Gly Cys Leu Met Lys Ser Ser Glu Asn Gly 35 40 45 Ala Leu Pro Val Val Ser Val Val Arg Glu Thr Glu Ser Gln Leu Leu 50 55 60 Pro Asp Val Gly Ala Ile Val Thr Cys Lys Val Ser Ser Ile Asn Ser 65 70 75 80 Arg Phe Ala Lys Val His Ile Leu Tyr Val Gly Ser Met Pro Leu Lys 85 90 95 Asn Ser Phe Arg Gly Thr Ile Arg Lys Glu Asp Val Arg Ala Thr Glu 100 105 110 Lys Asp Lys Val Glu Ile Tyr Lys Ser Phe Arg Pro Gly Asp Ile Val 115 120 125 Leu Ala Lys Val Ile Ser Leu Gly Asp Ala Gln Ser Asn Tyr Leu Leu 130 135 140 Thr Thr Ala Glu Asn Glu Leu Gly Val Val Val Ala His Ser Glu Ser 145 150 155 160 Gly Ile Gln Met Val Pro Ile Ser Trp Cys Glu Met Gln Cys Pro Lys 165 170 175 Thr His Thr Lys Glu Phe Arg Lys Val Ala Arg Val Gln Pro Glu Phe 180 185 190 Leu Gln Thr 195 <210> 81 <211> 3939 <212> PRT <213> Homo sapiens <400> 81 Met Ser Ser Ser Asp Glu Glu Thr Leu Ser Glu Arg Ser Cys Arg Ser 1 5 10 15 Glu Arg Ser Cys Arg Ser Glu Arg Ser Tyr Arg Ser Glu Arg Ser Gly 20 25 30 Ser Leu Ser Pro Cys Pro Pro Gly Asp Thr Leu Pro Trp Asn Leu Pro 35 40 45 Leu His Glu Gln Lys Lys Arg Lys Ser Gln Asp Ser Val Leu Asp Pro 50 55 60 Ala Glu Arg Ala Val Val Arg Val Ala Asp Glu Arg Asp Arg Val Gln 65 70 75 80 Lys Lys Thr Phe Thr Lys Trp Val Asn Lys His Leu Met Lys Val Arg 85 90 95 Lys His Ile Asn Asp Leu Tyr Glu Asp Leu Arg Asp Gly His Asn Leu 100 105 110 Ile Ser Leu Leu Glu Val Leu Ser Gly Ile Lys Leu Pro Arg Glu Lys 115 120 125 Gly Arg Met Arg Phe His Arg Leu Gln Asn Val Gln Ile Ala Leu Asp 130 135 140 Phe Leu Lys Gln Arg Gln Val Lys Leu Val Asn Ile Arg Asn Asp Asp 145 150 155 160 Ile Thr Asp Gly Asn Pro Lys Leu Thr Leu Gly Leu Ile Trp Thr Ile 165 170 175 Ile Leu His Phe Gln Ile Ser Asp Ile Tyr Ile Ser Gly Glu Ser Gly 180 185 190 Asp Met Ser Ala Lys Glu Lys Leu Leu Leu Trp Thr Gln Lys Val Thr 195 200 205 Ala Gly Tyr Thr Gly Ile Lys Cys Thr Asn Phe Ser Ser Cys Trp Ser 210 215 220 Asp Gly Lys Met Phe Asn Ala Leu Ile His Arg Tyr Arg Pro Asp Leu 225 230 235 240 Val Asp Met Glu Arg Val Gln Ile Gln Ser Asn Arg Glu Asn Leu Glu 245 250 255 Gln Ala Phe Glu Val Ala Glu Arg Leu Gly Val Thr Arg Leu Leu Asp 260 265 270 Ala Glu Asp Val Asp Val Pro Ser Pro Asp Glu Lys Ser Val Ile Thr 275 280 285 Tyr Val Ser Ser Ile Tyr Asp Ala Phe Pro Lys Val Pro Glu Gly Gly 290 295 300 Glu Gly Ile Ser Ala Thr Glu Val Asp Ser Arg Trp Gln Glu Tyr Gln 305 310 315 320 Ser Arg Val Asp Ser Leu Ile Pro Trp Ile Lys Gln His Thr Ile Leu 325 330 335 Met Ser Asp Lys Thr Phe Pro Gln Asn Pro Val Glu Leu Lys Ala Leu 340 345 350 Tyr Asn Gln Tyr Ile His Phe Lys Glu Thr Glu Ile Leu Ala Lys Glu 355 360 365 Arg Glu Lys Gly Arg Ile Glu Glu Leu Tyr Lys Leu Leu Glu Val Trp 370 375 380 Ile Glu Phe Gly Arg Ile Lys Leu Pro Gln Gly Tyr His Pro Asn Asp 385 390 395 400 Val Glu Glu Glu Trp Gly Lys Leu Ile Ile Glu Met Leu Glu Arg Glu 405 410 415 Lys Ser Leu Arg Pro Ala Val Glu Arg Leu Glu Leu Leu Leu Gln Ile 420 425 430 Ala Asn Lys Ile Gln Asn Gly Ala Leu Asn Cys Glu Glu Lys Leu Thr 435 440 445 Leu Ala Lys Asn Thr Leu Gln Ala Asp Ala Ala His Leu Glu Ser Gly 450 455 460 Gln Pro Val Gln Cys Glu Ser Asp Val Ile Met Tyr Ile Gln Glu Cys 465 470 475 480 Glu Gly Leu Ile Arg Gln Leu Gln Val Asp Leu Gln Ile Leu Arg Asp 485 490 495 Glu Asn Tyr Tyr Gln Leu Glu Glu Leu Ala Phe Arg Val Met Arg Leu 500 505 510 Gln Asp Glu Leu Val Thr Leu Arg Leu Glu Cys Thr Asn Leu Tyr Arg 515 520 525 Lys Gly His Phe Thr Ser Leu Glu Leu Val Pro Pro Ser Thr Leu Thr 530 535 540 Thr Thr His Leu Lys Ala Glu Pro Leu Thr Lys Ala Thr His Ser Ser 545 550 555 560 Ser Thr Ser Trp Phe Arg Lys Pro Met Thr Arg Ala Glu Leu Val Ala 565 570 575 Ile Ser Ser Ser Glu Asp Glu Gly Asn Leu Arg Phe Val Tyr Glu Leu 580 585 590 Leu Ser Trp Val Glu Glu Met Gln Met Lys Leu Glu Arg Ala Glu Trp 595 600 605 Gly Asn Asp Leu Pro Ser Val Glu Leu Gln Leu Glu Thr Gln Gln His 610 615 620 Ile His Thr Ser Val Glu Glu Leu Gly Ser Ser Val Lys Glu Ala Arg 625 630 635 640 Leu Tyr Glu Gly Lys Met Ser Gln Asn Phe His Thr Ser Tyr Ala Glu 645 650 655 Thr Leu Gly Lys Leu Glu Thr Gln Tyr Cys Lys Leu Lys Glu Thr Ser 660 665 670 Ser Phe Arg Met Arg His Leu Gln Ser Leu His Lys Phe Val Ser Arg 675 680 685 Ala Thr Ala Glu Leu Ile Trp Leu Asn Glu Lys Glu Glu Glu Glu Leu 690 695 700 Ala Tyr Asp Trp Ser Asp Asn Asn Ser Asn Ile Ser Ala Lys Arg Asn 705 710 715 720 Tyr Phe Ser Glu Leu Thr Met Glu Leu Glu Glu Lys Gln Asp Val Phe 725 730 735 Arg Ser Leu Gln Asp Thr Ala Glu Leu Leu Ser Leu Glu Asn His Pro 740 745 750 Ala Lys Gln Thr Val Glu Ala Tyr Ser Ala Ala Val Gln Ser Gln Leu 755 760 765 Gln Trp Met Lys Gln Leu Cys Leu Cys Val Glu Gln His Val Lys Glu 770 775 780 Asn Thr Ala Tyr Phe Gln Phe Phe Ser Asp Ala Arg Glu Leu Glu Ser 785 790 795 800 Phe Leu Arg Asn Leu Gln Asp Ser Ile Lys Arg Lys Tyr Ser Cys Asp 805 810 815 His Asn Thr Ser Leu Ser Arg Leu Glu Asp Leu Leu Gln Asp Ser Met 820 825 830 Asp Glu Lys Glu Gln Leu Ile Gln Ser Lys Ser Ser Val Ala Ser Leu 835 840 845 Val Gly Arg Ser Lys Thr Ile Val Gln Leu Lys Pro Arg Ser Pro Asp 850 855 860 His Val Leu Lys Asn Thr Ile Ser Val Lys Ala Val Cys Asp Tyr Arg 865 870 875 880 Gln Ile Glu Ile Thr Ile Cys Lys Asn Asp Glu Cys Val Leu Glu Asp 885 890 895 Asn Ser Gln Arg Thr Lys Trp Lys Val Ile Ser Pro Thr Gly Asn Glu 900 905 910 Ala Met Val Pro Ser Val Cys Phe Leu Ile Pro Pro Pro Asn Lys Asp 915 920 925 Ala Ile Glu Met Ala Ser Arg Val Glu Gln Ser Tyr Gln Lys Val Met 930 935 940 Ala Leu Trp His Gln Leu His Val Asn Thr Lys Ser Leu Ile Ser Trp 945 950 955 960 Asn Tyr Leu Arg Lys Asp Leu Asp Leu Val Gln Thr Trp Asn Leu Glu 965 970 975 Lys Leu Arg Ser Ser Ala Pro Gly Glu Cys His Gln Ile Met Lys Asn 980 985 990 Leu Gln Ala His Tyr Glu Asp Phe Leu Gln Asp Ser Arg Asp Ser Val 995 1000 1005 Leu Phe Ser Val Ala Asp Arg Leu Arg Leu Glu Glu Glu Val Glu Ala 1010 1015 1020 Cys Lys Ala Arg Phe Gln His Leu Met Lys Ser Met Glu Asn Glu Asp 1025 1030 1035 1040 Lys Glu Glu Thr Val Ala Lys Met Tyr Ile Ser Glu Leu Lys Asn Ile 1045 1050 1055 Arg Leu Arg Leu Glu Glu Tyr Glu Gln Arg Val Val Lys Arg Ile Gln 1060 1065 1070 Ser Leu Ala Ser Ser Arg Thr Asp Arg Asp Ala Trp Gln Asp Asn Ala 1075 1080 1085 Leu Arg Ile Ala Glu Gln Glu His Thr Gln Glu Asp Leu Gln Gln Leu 1090 1095 1100 Arg Ser Asp Leu Asp Ala Val Ser Met Lys Cys Asp Ser Phe Leu His 1105 1110 1115 1120 Gln Ser Pro Ser Ser Ser Ser Val Pro Thr Leu Arg Ser Glu Leu Asn 1125 1130 1135 Leu Leu Val Glu Lys Met Asp His Val Tyr Gly Leu Ser Thr Val Tyr 1140 1145 1150 Leu Asn Lys Leu Lys Thr Val Asp Val Ile Val Arg Ser Ile Gln Asp 1155 1160 1165 Ala Glu Leu Leu Val Lys Gly Tyr Glu Ile Lys Leu Ser Gln Glu Glu 1170 1175 1180 Val Val Leu Ala Asp Leu Ser Ala Leu Glu Ala His Trp Ser Thr Leu 1185 1190 1195 1200 Arg His Trp Leu Ser Asp Val Lys Asp Lys Asn Ser Val Phe Ser Val 1205 1210 1215 Leu Asp Glu Glu Ile Ala Lys Ala Lys Val Val Ala Glu Gln Met Ser 1220 1225 1230 Arg Leu Thr Pro Glu Arg Asn Leu Asp Leu Glu Arg Tyr Gln Glu Lys 1235 1240 1245 Gly Ser Gln Leu Gln Glu Arg Trp His Arg Val Ile Ala Gln Leu Glu 1250 1255 1260 Ile Arg Gln Ser Glu Leu Glu Ser Ile Gln Glu Val Leu Gly Asp Tyr 1265 1270 1275 1280 Arg Ala Cys His Gly Thr Leu Ile Lys Trp Ile Glu Glu Thr Thr Ala 1285 1290 1295 Gln Gln Glu Met Met Lys Pro Gly Gln Ala Glu Asp Ser Arg Val Leu 1300 1305 1310 Ser Glu Gln Leu Ser Gln Gln Thr Ala Leu Phe Ala Glu Ile Glu Arg 1315 1320 1325 Asn Gln Thr Lys Leu Asp Gln Cys Gln Lys Phe Ser Gln Gln Tyr Ser 1330 1335 1340 Thr Ile Val Lys Asp Tyr Glu Leu Gln Leu Met Thr Tyr Lys Ala Phe 1345 1350 1355 1360 Val Glu Ser Gln Gln Lys Ser Pro Gly Lys Arg Arg Arg Met Leu Ser 1365 1370 1375 Ser Ser Asp Ala Ile Thr Gln Glu Phe Met Asp Leu Arg Thr Arg Tyr 1380 1385 1390 Thr Ala Leu Val Thr Leu Thr Thr Gln His Val Lys Tyr Ile Ser Asp 1395 1400 1405 Ala Leu Arg Arg Leu Glu Glu Glu Glu Lys Val Val Glu Glu Glu Lys 1410 1415 1420 Gln Glu His Val Glu Lys Val Lys Glu Leu Leu Gly Trp Val Ser Thr 1425 1430 1435 1440 Leu Ala Arg Asn Thr Gln Gly Lys Ala Thr Ser Ser Glu Thr Lys Glu 1445 1450 1455 Ser Thr Asp Ile Glu Lys Ala Ile Leu Glu Gln Gln Val Leu Ser Glu 1460 1465 1470 Glu Leu Thr Thr Lys Lys Glu Gln Val Ser Glu Ala Ile Lys Thr Ser 1475 1480 1485 Gln Ile Phe Leu Ala Lys His Gly His Lys Leu Ser Glu Lys Glu Lys 1490 1495 1500 Lys Gln Ile Ser Glu Gln Leu Asn Ala Leu Asn Lys Ala Tyr His Asp 1505 1510 1515 1520 Leu Cys Asp Gly Ser Ala Asn Gln Leu Gln Gln Leu Gln Ser Gln Leu 1525 1530 1535 Ala His Gln Thr Glu Gln Lys Thr Leu Gln Lys Gln Gln Asn Thr Cys 1540 1545 1550 His Gln Gln Leu Glu Asp Leu Cys Ser Trp Val Gly Gln Ala Glu Arg 1555 1560 1565 Ala Leu Ala Gly His Gln Gly Arg Thr Thr Gln Gln Asp Leu Ser Ala 1570 1575 1580 Leu Gln Lys Asn Gln Ser Asp Leu Lys Asp Leu Gln Asp Asp Ile Gln 1585 1590 1595 1600 Asn Arg Ala Thr Ser Phe Ala Thr Val Val Lys Asp Ile Glu Gly Phe 1605 1610 1615 Met Glu Glu Asn Gln Thr Lys Leu Ser Pro Arg Glu Leu Thr Ala Leu 1620 1625 1630 Arg Glu Lys Leu His Gln Ala Lys Glu Gln Tyr Glu Ala Leu Gln Glu 1635 1640 1645 Glu Thr Arg Val Ala Gln Lys Glu Leu Glu Glu Ala Val Thr Ser Ala 1650 1655 1660 Leu Gln Gln Glu Thr Glu Lys Ser Lys Ala Ala Lys Glu Leu Ala Glu 1665 1670 1675 1680 Asn Lys Lys Lys Ile Asp Ala Leu Leu Asp Trp Val Thr Ser Val Gly 1685 1690 1695 Ser Ser Gly Gly Gln Leu Leu Thr Asn Leu Pro Gly Met Glu Gln Leu 1700 1705 1710 Ser Gly Ala Ser Leu Glu Lys Gly Ala Leu Asp Thr Thr Asp Gly Tyr 1715 1720 1725 Met Gly Val Asn Gln Ala Pro Glu Lys Leu Asp Lys Gln Cys Glu Met 1730 1735 1740 Met Lys Ala Arg His Gln Glu Leu Leu Ser Gln Gln Gln Asn Phe Ile 1745 1750 1755 1760 Leu Ala Thr Gln Ser Ala Gln Ala Phe Leu Asp Gln His Gly His Asn 1765 1770 1775 Leu Thr Pro Glu Glu Gln Gln Met Leu Gln Gln Lys Leu Gly Glu Leu 1780 1785 1790 Lys Glu Gln Tyr Ser Thr Ser Leu Ala Gln Ser Glu Ala Glu Leu Lys 1795 1800 1805 Gln Val Gln Thr Leu Gln Asp Glu Leu Gln Lys Phe Leu Gln Asp His 1810 1815 1820 Lys Glu Phe Glu Ser Trp Leu Glu Arg Ser Glu Lys Glu Leu Glu Asn 1825 1830 1835 1840 Met His Lys Gly Gly Ser Ser Pro Glu Thr Leu Pro Ser Leu Leu Lys 1845 1850 1855 Arg Gln Gly Ser Phe Ser Glu Asp Val Ile Ser His Lys Gly Asp Leu 1860 1865 1870 Arg Phe Val Thr Ile Ser Gly Gln Lys Val Leu Asp Met Glu Asn Ser 1875 1880 1885 Phe Lys Glu Gly Lys Glu Pro Ser Glu Ile Gly Asn Leu Val Lys Asp 1890 1895 1900 Lys Leu Lys Asp Ala Thr Glu Arg Tyr Thr Ala Leu His Ser Lys Cys 1905 1910 1915 1920 Thr Arg Leu Gly Ser His Leu Asn Met Leu Leu Gly Gln Tyr His Gln 1925 1930 1935 Phe Gln Asn Ser Ala Asp Ser Leu Gln Ala Trp Met Gln Ala Cys Glu 1940 1945 1950 Ala Asn Val Glu Lys Leu Leu Ser Asp Thr Val Ala Ser Asp Pro Gly 1955 1960 1965 Val Leu Gln Glu Gln Leu Ala Thr Thr Lys Gln Leu Gln Glu Glu Leu 1970 1975 1980 Ala Glu His Gln Val Pro Val Glu Lys Leu Gln Lys Val Ala Arg Asp 1985 1990 1995 2000 Ile Met Glu Ile Glu Gly Glu Pro Ala Pro Asp His Arg His Val Gln 2005 2010 2015 Glu Thr Thr Asp Ser Ile Leu Ser His Phe Gln Ser Leu Ser Tyr Ser 2020 2025 2030 Leu Ala Glu Arg Ser Ser Leu Leu Gln Lys Ala Ile Ala Gln Ser Gln 2035 2040 2045 Ser Val Gln Glu Ser Leu Glu Ser Leu Leu Gln Ser Ile Gly Glu Val 2050 2055 2060 Glu Gln Asn Leu Glu Gly Lys Gln Val Ser Ser Leu Ser Ser Gly Val 2065 2070 2075 2080 Ile Gln Glu Ala Leu Ala Thr Asn Met Lys Leu Lys Gln Asp Ile Ala 2085 2090 2095 Arg Gln Lys Ser Ser Leu Glu Ala Thr Arg Glu Met Val Thr Arg Phe 2100 2105 2110 Met Glu Thr Ala Asp Ser Thr Thr Ala Ala Val Leu Gln Gly Lys Leu 2115 2120 2125 Ala Glu Val Ser Gln Arg Phe Glu Gln Leu Cys Leu Gln Gln Gln Glu 2130 2135 2140 Lys Glu Ser Ser Leu Lys Lys Leu Leu Pro Gln Ala Glu Met Phe Glu 2145 2150 2155 2160 His Leu Ser Gly Lys Leu Gln Gln Phe Met Glu Asn Lys Ser Arg Met 2165 2170 2175 Leu Ala Ser Gly Asn Gln Pro Asp Gln Asp Ile Thr His Phe Phe Gln 2180 2185 2190 Gln Ile Gln Glu Leu Asn Leu Glu Met Glu Asp Gln Gln Glu Asn Leu 2195 2200 2205 Asp Thr Leu Glu His Leu Val Thr Glu Leu Ser Ser Cys Gly Phe Ala 2210 2215 2220 Leu Asp Leu Cys Gln His Gln Asp Arg Val Gln Asn Leu Arg Lys Asp 2225 2230 2235 2240 Phe Thr Glu Leu Gln Lys Thr Val Lys Glu Arg Glu Lys Asp Ala Ser 2245 2250 2255 Ser Cys Gln Glu Gln Leu Asp Glu Phe Arg Lys Leu Val Arg Thr Phe 2260 2265 2270 Gln Lys Trp Leu Lys Glu Thr Glu Gly Ser Ile Pro Pro Thr Glu Thr 2275 2280 2285 Ser Met Ser Ala Lys Glu Leu Glu Lys Gln Ile Glu His Leu Lys Ser 2290 2295 2300 Leu Leu Asp Asp Trp Ala Ser Lys Gly Thr Leu Val Glu Glu Ile Asn 2305 2310 2315 2320 Cys Lys Gly Thr Ser Leu Glu Asn Leu Ile Met Glu Ile Thr Ala Pro 2325 2330 2335 Asp Ser Gln Gly Lys Thr Gly Ser Ile Leu Pro Ser Val Gly Ser Ser 2340 2345 2350 Val Gly Ser Val Asn Gly Tyr His Thr Cys Lys Asp Leu Thr Glu Ile 2355 2360 2365 Gln Cys Asp Met Ser Asp Val Asn Leu Lys Tyr Glu Lys Leu Gly Gly 2370 2375 2380 Val Leu His Glu Arg Gln Glu Ser Leu Gln Ala Ile Leu Asn Arg Met 2385 2390 2395 2400 Glu Glu Val His Lys Glu Ala Asn Ser Val Leu Gln Trp Leu Glu Ser 2405 2410 2415 Lys Glu Glu Val Leu Lys Ser Met Asp Ala Met Ser Ser Pro Thr Lys 2420 2425 2430 Thr Glu Thr Val Lys Ala Gln Ala Glu Ser Asn Lys Ala Phe Leu Ala 2435 2440 2445 Glu Leu Glu Gln Asn Ser Pro Lys Ile Gln Lys Val Lys Glu Ala Leu 2450 2455 2460 Ala Gly Leu Leu Val Thr Tyr Pro Asn Ser Gln Glu Ala Glu Asn Trp 2465 2470 2475 2480 Lys Lys Ile Gln Glu Glu Leu Asn Ser Arg Trp Glu Arg Ala Thr Glu 2485 2490 2495 Val Thr Val Ala Arg Gln Arg Gln Leu Glu Glu Ser Ala Ser His Leu 2500 2505 2510 Ala Cys Phe Gln Ala Ala Glu Ser Gln Leu Arg Pro Trp Leu Met Glu 2515 2520 2525 Lys Glu Leu Met Met Gly Val Leu Gly Pro Leu Ser Ile Asp Pro Asn 2530 2535 2540 Met Leu Asn Ala Gln Lys Gln Gln Val Gln Phe Met Leu Lys Glu Phe 2545 2550 2555 2560 Glu Ala Arg Arg Gln Gln His Glu Gln Leu Asn Glu Ala Ala Gln Gly 2565 2570 2575 Ile Leu Thr Gly Pro Gly Asp Val Ser Leu Ser Thr Ser Gln Val Gln 2580 2585 2590 Lys Glu Leu Gln Ser Ile Asn Gln Lys Trp Val Glu Leu Thr Asp Lys 2595 2600 2605 Leu Asn Ser Arg Ser Ser Gln Ile Asp Gln Ala Ile Val Lys Ser Thr 2610 2615 2620 Gln Tyr Gln Glu Leu Leu Gln Asp Leu Ser Glu Lys Val Arg Ala Val 2625 2630 2635 2640 Gly Gln Arg Leu Ser Val Gln Ser Ala Ile Ser Thr Gln Pro Glu Ala 2645 2650 2655 Val Lys Gln Gln Leu Glu Glu Thr Ser Glu Ile Arg Ser Asp Leu Glu 2660 2665 2670 Gln Leu Asp His Glu Val Lys Glu Ala Gln Thr Leu Cys Asp Glu Leu 2675 2680 2685 Ser Val Leu Ile Gly Glu Gln Tyr Leu Lys Asp Glu Leu Lys Lys Arg 2690 2695 2700 Leu Glu Thr Val Ala Leu Pro Leu Gln Gly Leu Glu Asp Leu Ala Ala 2705 2710 2715 2720 Asp Arg Ile Asn Arg Leu Gln Ala Ala Leu Ala Ser Thr Gln Gln Phe 2725 2730 2735 Gln Gln Met Phe Asp Glu Leu Arg Thr Trp Leu Asp Asp Lys Gln Ser 2740 2745 2750 Gln Gln Ala Lys Asn Cys Pro Ile Ser Ala Lys Leu Glu Arg Leu Gln 2755 2760 2765 Ser Gln Leu Gln Glu Asn Glu Glu Phe Gln Lys Ser Leu Asn Gln His 2770 2775 2780 Ser Gly Ser Tyr Glu Val Ile Val Ala Glu Gly Glu Ser Leu Leu Leu 2785 2790 2795 2800 Ser Val Pro Pro Gly Glu Glu Lys Arg Thr Leu Gln Asn Gln Leu Val 2805 2810 2815 Glu Leu Lys Asn His Trp Glu Glu Leu Ser Lys Lys Thr Ala Asp Arg 2820 2825 2830 Gln Ser Arg Leu Lys Asp Cys Met Gln Lys Ala Gln Lys Tyr Gln Trp 2835 2840 2845 His Val Glu Asp Leu Val Pro Trp Ile Glu Asp Cys Lys Ala Lys Met 2850 2855 2860 Ser Glu Leu Arg Val Thr Leu Asp Pro Val Gln Leu Glu Ser Ser Leu 2865 2870 2875 2880 Leu Arg Ser Lys Ala Met Leu Asn Glu Val Glu Lys Arg Arg Ser Leu 2885 2890 2895 Leu Glu Ile Leu Asn Ser Ala Ala Asp Ile Leu Ile Asn Ser Ser Glu 2900 2905 2910 Ala Asp Glu Asp Gly Ile Arg Asp Glu Lys Ala Gly Ile Asn Gln Asn 2915 2920 2925 Met Asp Ala Val Thr Glu Glu Leu Gln Ala Lys Thr Gly Ser Leu Glu 2930 2935 2940 Glu Met Thr Gln Arg Leu Arg Glu Phe Gln Glu Ser Phe Lys Asn Ile 2945 2950 2955 2960 Glu Lys Lys Val Glu Gly Ala Lys His Gln Leu Glu Ile Phe Asp Ala 2965 2970 2975 Leu Gly Ser Gln Ala Cys Ser Asn Lys Asn Leu Glu Lys Leu Arg Ala 2980 2985 2990 Gln Gln Glu Val Leu Gln Ala Leu Glu Pro Gln Val Asp Tyr Leu Arg 2995 3000 3005 Asn Phe Thr Gln Gly Leu Val Glu Asp Ala Pro Asp Gly Ser Asp Ala 3010 3015 3020 Ser Gln Leu Leu His Gln Ala Glu Val Ala Gln Gln Glu Phe Leu Glu 3025 3030 3035 3040 Val Lys Gln Arg Val Asn Ser Gly Cys Val Met Met Glu Asn Lys Leu 3045 3050 3055 Glu Gly Ile Gly Gln Phe His Cys Arg Val Arg Glu Met Phe Ser Gln 3060 3065 3070 Leu Ala Asp Leu Asp Asp Glu Leu Asp Gly Met Gly Ala Ile Gly Arg 3075 3080 3085 Asp Thr Asp Ser Leu Gln Ser Gln Ile Glu Asp Val Arg Leu Phe Leu 3090 3095 3100 Asn Lys Ile His Val Leu Lys Leu Asp Ile Glu Ala Ser Glu Ala Glu 3105 3110 3115 3120 Cys Arg His Met Leu Glu Glu Glu Gly Thr Leu Asp Leu Leu Gly Leu 3125 3130 3135 Lys Arg Glu Leu Glu Ala Leu Asn Lys Gln Cys Gly Lys Leu Thr Glu 3140 3145 3150 Arg Gly Lys Ala Arg Gln Glu Gln Leu Glu Leu Thr Leu Gly Arg Val 3155 3160 3165 Glu Asp Phe Tyr Arg Lys Leu Lys Gly Leu Asn Asp Ala Thr Thr Ala 3170 3175 3180 Ala Glu Glu Ala Glu Ala Leu Gln Trp Val Val Gly Thr Glu Val Glu 3185 3190 3195 3200 Ile Ile Asn Gln Gln Leu Ala Asp Phe Lys Met Phe Gln Lys Glu Gln 3205 3210 3215 Val Asp Pro Leu Gln Met Lys Leu Gln Gln Val Asn Gly Leu Gly Gln 3220 3225 3230 Gly Leu Ile Gln Ser Ala Gly Lys Asp Cys Asp Val Gln Gly Leu Glu 3235 3240 3245 His Asp Met Glu Glu Ile Asn Ala Arg Trp Asn Thr Leu Asn Lys Lys 3250 3255 3260 Val Ala Gln Arg Ile Ala Gln Leu Gln Glu Ala Leu Leu His Cys Gly 3265 3270 3275 3280 Lys Phe Gln Asp Ala Leu Glu Pro Leu Leu Ser Trp Leu Ala Asp Thr 3285 3290 3295 Glu Glu Leu Ile Ala Asn Gln Lys Pro Pro Ser Ala Glu Tyr Lys Val 3300 3305 3310 Val Lys Ala Gln Ile Gln Glu Gln Lys Leu Leu Gln Arg Leu Leu Asp 3315 3320 3325 Asp Arg Lys Ala Thr Val Asp Met Leu Gln Ala Glu Gly Gly Arg Ile 3330 3335 3340 Ala Gln Ser Ala Glu Leu Ala Asp Arg Glu Lys Ile Thr Gly Gln Leu 3345 3350 3355 3360 Glu Ser Leu Glu Ser Arg Trp Thr Glu Leu Leu Ser Lys Ala Ala Ala 3365 3370 3375 Arg Gln Lys Gln Leu Glu Asp Ile Leu Val Leu Ala Lys Gln Phe His 3380 3385 3390 Glu Thr Ala Glu Pro Ile Ser Asp Phe Leu Ser Val Thr Glu Lys Lys 3395 3400 3405 Leu Ala Asn Ser Glu Pro Val Gly Thr Gln Thr Ala Lys Ile Gln Gln 3410 3415 3420 Gln Ile Ile Arg His Lys Ala Leu Glu Glu Asp Ile Glu Asn His Ala 3425 3430 3435 3440 Thr Asp Val His Gln Ala Val Lys Ile Gly Gln Ser Leu Ser Ser Leu 3445 3450 3455 Thr Ser Pro Ala Glu Gln Gly Val Leu Ser Glu Lys Ile Asp Ser Leu 3460 3465 3470 Gln Ala Arg Tyr Ser Glu Ile Gln Asp Arg Cys Cys Arg Lys Ala Ala 3475 3480 3485 Leu Leu Asp Gln Ala Leu Ser Asn Ala Arg Leu Phe Gly Glu Asp Glu 3490 3495 3500 Val Glu Val Leu Asn Trp Leu Ala Glu Val Glu Asp Lys Leu Ser Ser 3505 3510 3515 3520 Val Phe Val Lys Asp Phe Lys Gln Asp Val Leu His Arg Gln His Ala 3525 3530 3535 Asp His Leu Ala Leu Asn Glu Glu Ile Val Asn Arg Lys Lys Asn Val 3540 3545 3550 Asp Gln Ala Ile Lys Asn Gly Gln Ala Leu Leu Lys Gln Thr Thr Gly 3555 3560 3565 Glu Glu Val Leu Leu Ile Gln Glu Lys Leu Asp Gly Ile Lys Thr Arg 3570 3575 3580 Tyr Ala Asp Ile Thr Val Thr Ser Ser Lys Ala Leu Arg Thr Leu Glu 3585 3590 3595 3600 Gln Ala Arg Gln Leu Ala Thr Lys Phe Gln Ser Thr Tyr Glu Glu Leu 3605 3610 3615 Thr Gly Trp Leu Arg Glu Val Glu Glu Glu Leu Ala Thr Ser Gly Gly 3620 3625 3630 Gln Ser Pro Thr Gly Glu Gln Ile Pro Gln Phe Gln Gln Arg Gln Lys 3635 3640 3645 Glu Leu Lys Lys Glu Val Met Glu His Arg Leu Val Leu Asp Thr Val 3650 3655 3660 Asn Glu Val Ser Arg Ala Leu Leu Glu Leu Val Pro Trp Arg Ala Arg 3665 3670 3675 3680 Glu Gly Leu Asp Lys Leu Val Ser Asp Ala Asn Glu Gln Tyr Lys Leu 3685 3690 3695 Val Ser Asp Thr Ile Gly Gln Arg Val Asp Glu Ile Asp Ala Ala Ile 3700 3705 3710 Gln Arg Ser Gln Gln Tyr Glu Gln Ala Ala Asp Ala Glu Leu Ala Trp 3715 3720 3725 Val Ala Glu Thr Lys Arg Lys Leu Met Ala Leu Gly Pro Ile Arg Leu 3730 3735 3740 Glu Gln Asp Gln Thr Thr Ala Gln Leu Gln Val Gln Lys Ala Phe Ser 3745 3750 3755 3760 Ile Asp Ile Ile Arg His Lys Asp Ser Met Asp Glu Leu Phe Ser His 3765 3770 3775 Arg Ser Glu Ile Phe Gly Thr Cys Gly Glu Glu Gln Lys Thr Val Leu 3780 3785 3790 Gln Glu Lys Thr Glu Ser Leu Ile Gln Gln Tyr Glu Ala Ile Ser Leu 3795 3800 3805 Leu Asn Ser Glu Arg Tyr Ala Arg Leu Glu Arg Ala Gln Val Leu Val 3810 3815 3820 Asn Gln Phe Trp Glu Thr Tyr Glu Glu Leu Ser Pro Trp Ile Glu Glu 3825 3830 3835 3840 Thr Arg Ala Leu Ile Ala Gln Leu Pro Ser Pro Ala Ile Asp His Glu 3845 3850 3855 Gln Leu Arg Gln Gln Gln Glu Glu Met Arg Gln Leu Arg Glu Ser Ile 3860 3865 3870 Ala Glu His Lys Pro His Ile Asp Lys Leu Leu Lys Ile Gly Pro Gln 3875 3880 3885 Leu Lys Glu Leu Asn Pro Glu Glu Gly Glu Met Val Glu Glu Lys Tyr 3890 3895 3900 Gln Lys Ala Glu Asn Met Tyr Ala Gln Ile Lys Glu Glu Val Arg Gln 3905 3910 3915 3920 Arg Ala Leu Ala Leu Asp Glu Ala Val Ser Gln Ser Thr Gln Ile Cys 3925 3930 3935 Leu Val Ser <210> 82 <211> 377 <212> PRT <213> Homo sapiens <400> 82 Met Cys Glu Glu Glu Asp Ser Thr Ala Leu Val Cys Asp Asn Gly Ser 1 5 10 15 Gly Leu Cys Lys Ala Gly Phe Ala Gly Asp Asp Ala Pro Arg Ala Val 20 25 30 Phe Pro Ser Ile Val Gly Arg Pro Arg His Gln Gly Val Met Val Gly 35 40 45 Met Gly Gln Lys Asp Ser Tyr Val Gly Asp Glu Ala Gln Ser Lys Arg 50 55 60 Gly Ile Leu Thr Leu Lys Tyr Pro Ile Glu His Gly Ile Ile Thr Asn 65 70 75 80 Trp Asp Asp Met Glu Lys Ile Trp His His Ser Phe Tyr Asn Glu Leu 85 90 95 Arg Val Ala Pro Glu Glu His Pro Thr Leu Leu Thr Glu Ala Pro Leu 100 105 110 Asn Pro Lys Ala Asn Arg Glu Lys Met Thr Gln Ile Met Phe Glu Thr 115 120 125 Phe Asn Val Pro Ala Met Tyr Val Ala Ile Gln Ala Val Leu Ser Leu 130 135 140 Tyr Ala Ser Gly Arg Thr Thr Gly Ile Val Leu Asp Ser Gly Asp Gly 145 150 155 160 Val Thr His Asn Val Pro Ile Tyr Glu Gly Tyr Ala Leu Pro His Ala 165 170 175 Ile Met Arg Leu Asp Leu Ala Gly Arg Asp Leu Thr Asp Tyr Leu Met 180 185 190 Lys Ile Leu Thr Glu Arg Gly Tyr Ser Phe Val Thr Thr Ala Glu Arg 195 200 205 Glu Ile Val Arg Asp Ile Lys Glu Lys Leu Cys Tyr Val Ala Leu Asp 210 215 220 Phe Glu Asn Glu Met Ala Thr Ala Ala Ser Ser Ser Ser Leu Glu Lys 225 230 235 240 Ser Tyr Glu Leu Pro Asp Gly Gln Val Ile Thr Ile Gly Asn Glu Arg 245 250 255 Phe Arg Cys Pro Glu Thr Leu Phe Gln Pro Ser Phe Ile Gly Met Glu 260 265 270 Ser Ala Gly Ile His Glu Thr Thr Tyr Asn Ser Ile Met Lys Cys Asp 275 280 285 Ile Asp Ile Arg Lys Asp Leu Tyr Ala Asn Asn Val Leu Ser Gly Gly 290 295 300 Thr Thr Met Tyr Pro Gly Ile Ala Asp Arg Met Gln Lys Glu Ile Thr 305 310 315 320 Ala Leu Ala Pro Ser Thr Met Lys Ile Lys Ile Ile Ala Pro Pro Glu 325 330 335 Arg Lys Tyr Ser Val Trp Ile Gly Gly Ser Ile Leu Ala Ser Leu Ser 340 345 350 Thr Phe Gln Gln Met Trp Ile Ser Lys Gln Glu Tyr Asp Glu Ala Gly 355 360 365 Pro Ser Ile Val His Arg Lys Cys Phe 370 375 <210> 83 <211> 2436 <212> PRT <213> Homo sapiens <400> 83 Met Gly Phe Leu His Gln Leu Gln Leu Leu Leu Trp Lys Asn Val Thr 1 5 10 15 Leu Lys Arg Arg Ser Pro Trp Val Leu Ala Phe Glu Ile Phe Ile Pro 20 25 30 Leu Val Leu Phe Phe Ile Leu Leu Gly Leu Arg Gln Lys Lys Pro Thr 35 40 45 Ile Ser Val Lys Glu Val Ser Phe Tyr Thr Ala Ala Pro Leu Thr Ser 50 55 60 Ala Gly Ile Leu Pro Val Met Gln Ser Leu Cys Pro Asp Gly Gln Arg 65 70 75 80 Asp Glu Phe Gly Phe Leu Gln Tyr Ala Asn Ser Thr Val Thr Gln Leu 85 90 95 Leu Glu Arg Leu Asp Arg Val Val Glu Glu Gly Asn Leu Phe Asp Pro 100 105 110 Ala Arg Pro Ser Leu Gly Ser Glu Leu Glu Ala Leu Arg Gln His Leu 115 120 125 Glu Ala Leu Ser Ala Gly Pro Gly Thr Ser Gly Ser His Leu Asp Arg 130 135 140 Ser Thr Val Ser Ser Phe Ser Leu Asp Ser Val Ala Arg Asn Pro Gln 145 150 155 160 Glu Leu Trp Arg Phe Leu Thr Gln Asn Leu Ser Leu Pro Asn Ser Thr 165 170 175 Ala Gln Ala Leu Leu Ala Ala Arg Val Asp Pro Pro Glu Val Tyr His 180 185 190 Leu Leu Phe Gly Pro Ser Ser Ala Leu Asp Ser Gln Ser Gly Leu His 195 200 205 Lys Gly Gln Glu Pro Trp Ser Arg Leu Gly Gly Asn Pro Leu Phe Arg 210 215 220 Met Glu Glu Leu Leu Leu Ala Pro Ala Leu Leu Glu Gln Leu Thr Cys 225 230 235 240 Thr Pro Gly Ser Gly Glu Leu Gly Arg Ile Leu Thr Val Pro Glu Ser 245 250 255 Gln Lys Gly Ala Leu Gln Gly Tyr Arg Asp Ala Val Cys Ser Gly Gln 260 265 270 Ala Ala Ala Arg Ala Arg Arg Phe Ser Gly Leu Ser Ala Glu Leu Arg 275 280 285 Asn Gln Leu Asp Val Ala Lys Val Ser Gln Gln Leu Gly Leu Asp Ala 290 295 300 Pro Asn Gly Ser Asp Ser Ser Pro Gln Ala Pro Pro Pro Arg Arg Leu 305 310 315 320 Gln Ala Leu Leu Gly Asp Leu Leu Asp Ala Gln Lys Val Leu Gln Asp 325 330 335 Val Asp Val Leu Ser Ala Leu Ala Leu Leu Leu Pro Gln Gly Ala Cys 340 345 350 Thr Gly Arg Thr Pro Gly Pro Pro Ala Ser Gly Ala Gly Gly Ala Ala 355 360 365 Asn Gly Thr Gly Ala Gly Ala Val Met Gly Pro Asn Ala Thr Ala Glu 370 375 380 Glu Gly Ala Pro Ser Ala Ala Ala Leu Ala Thr Pro Asp Thr Leu Gln 385 390 395 400 Gly Gln Cys Ser Ala Phe Val Gln Leu Trp Ala Gly Leu Gln Pro Ile 405 410 415 Leu Cys Gly Asn Asn Arg Thr Ile Glu Pro Glu Ala Leu Arg Arg Gly 420 425 430 Asn Met Ser Ser Leu Gly Phe Thr Ser Lys Glu Gln Arg Asn Leu Gly 435 440 445 Leu Leu Val His Leu Met Thr Ser Asn Pro Lys Ile Leu Tyr Ala Pro 450 455 460 Ala Gly Ser Glu Val Asp Arg Val Ile Leu Lys Ala Asn Glu Thr Phe 465 470 475 480 Ala Phe Val Gly Asn Val Thr His Tyr Ala Gln Val Trp Leu Asn Ile 485 490 495 Ser Ala Glu Ile Arg Ser Phe Leu Glu Gln Gly Arg Leu Gln Gln His 500 505 510 Leu Arg Trp Leu Gln Gln Tyr Val Ala Glu Leu Arg Leu His Pro Glu 515 520 525 Ala Leu Asn Leu Ser Leu Asp Glu Leu Pro Pro Ala Leu Arg Gln Asp 530 535 540 Asn Phe Ser Leu Pro Ser Gly Met Ala Leu Leu Gln Gln Leu Asp Thr 545 550 555 560 Ile Asp Asn Ala Ala Cys Gly Trp Ile Gln Phe Met Ser Lys Val Ser 565 570 575 Val Asp Ile Phe Lys Gly Phe Pro Asp Glu Glu Ser Ile Val Asn Tyr 580 585 590 Thr Leu Asn Gln Ala Tyr Gln Asp Asn Val Thr Val Phe Ala Ser Val 595 600 605 Ile Phe Gln Thr Arg Lys Asp Gly Ser Leu Pro Pro His Val His Tyr 610 615 620 Lys Ile Arg Gln Asn Ser Ser Phe Thr Glu Lys Thr Asn Glu Ile Arg 625 630 635 640 Arg Ala Tyr Trp Arg Pro Gly Pro Asn Thr Gly Gly Arg Phe Tyr Phe 645 650 655 Leu Tyr Gly Phe Val Trp Ile Gln Asp Met Met Glu Arg Ala Ile Ile 660 665 670 Asp Thr Phe Val Gly His Asp Val Val Glu Pro Gly Ser Tyr Val Gln 675 680 685 Met Phe Pro Tyr Pro Cys Tyr Thr Arg Asp Asp Phe Leu Phe Val Ile 690 695 700 Glu His Met Met Pro Leu Cys Met Val Ile Ser Trp Val Tyr Ser Val 705 710 715 720 Ala Met Thr Ile Gln His Ile Val Ala Glu Lys Glu His Arg Leu Lys 725 730 735 Glu Val Met Lys Thr Met Gly Leu Asn Asn Ala Val His Trp Val Ala 740 745 750 Trp Phe Ile Thr Gly Phe Val Gln Leu Ser Ile Ser Val Thr Ala Leu 755 760 765 Thr Ala Ile Leu Lys Tyr Gly Gln Val Leu Met His Ser His Val Val 770 775 780 Ile Ile Trp Leu Phe Leu Ala Val Tyr Ala Val Ala Thr Ile Met Phe 785 790 795 800 Cys Phe Leu Val Ser Val Leu Tyr Ser Lys Ala Lys Leu Ala Ser Ala 805 810 815 Cys Gly Gly Ile Ile Tyr Phe Leu Ser Tyr Val Pro Tyr Met Tyr Val 820 825 830 Ala Ile Arg Glu Glu Val Ala His Asp Lys Ile Thr Ala Phe Glu Lys 835 840 845 Cys Ile Ala Ser Leu Met Ser Thr Thr Ala Phe Gly Leu Gly Ser Lys 850 855 860 Tyr Phe Ala Leu Tyr Glu Val Ala Gly Val Gly Ile Gln Trp His Thr 865 870 875 880 Phe Ser Gln Ser Pro Val Glu Gly Asp Asp Phe Asn Leu Leu Leu Ala 885 890 895 Val Thr Met Leu Met Val Asp Ala Val Val Tyr Gly Ile Leu Thr Trp 900 905 910 Tyr Ile Glu Ala Val His Pro Gly Met Tyr Gly Leu Pro Arg Pro Trp 915 920 925 Tyr Phe Pro Leu Gln Lys Ser Tyr Trp Leu Gly Ser Gly Arg Thr Glu 930 935 940 Ala Trp Glu Trp Ser Trp Pro Trp Ala Arg Thr Pro Arg Leu Ser Val 945 950 955 960 Met Glu Glu Asp Gln Ala Cys Ala Met Glu Ser Arg Arg Phe Glu Glu 965 970 975 Thr Arg Gly Met Glu Glu Glu Pro Thr His Leu Pro Leu Val Val Cys 980 985 990 Val Asp Lys Leu Thr Lys Val Tyr Lys Asp Asp Lys Lys Leu Ala Leu 995 1000 1005 Asn Lys Leu Ser Leu Asn Leu Tyr Glu Asn Gln Val Val Ser Phe Leu 1010 1015 1020 Gly His Asn Gly Ala Gly Lys Thr Thr Thr Met Ser Ile Leu Thr Gly 1025 1030 1035 1040 Leu Phe Pro Pro Thr Ser Gly Ser Ala Thr Ile Tyr Gly His Asp Ile 1045 1050 1055 Arg Thr Glu Met Asp Glu Ile Arg Lys Asn Leu Gly Met Cys Pro Gln 1060 1065 1070 His Asn Val Leu Phe Asp Arg Leu Thr Val Glu Glu His Leu Trp Phe 1075 1080 1085 Tyr Ser Arg Leu Lys Ser Met Ala Gln Glu Glu Ile Arg Arg Glu Met 1090 1095 1100 Asp Lys Met Ile Glu Asp Leu Glu Leu Ser Asn Lys Arg His Ser Leu 1105 1110 1115 1120 Val Gln Thr Leu Ser Gly Gly Met Lys Arg Lys Leu Ser Val Ala Ile 1125 1130 1135 Ala Phe Val Gly Gly Ser Arg Ala Ile Ile Leu Asp Glu Pro Thr Ala 1140 1145 1150 Gly Val Asp Pro Tyr Ala Arg Arg Ala Ile Trp Asp Leu Ile Leu Lys 1155 1160 1165 Tyr Lys Pro Gly Arg Thr Ile Leu Leu Ser Thr His His Met Asp Glu 1170 1175 1180 Ala Asp Leu Leu Gly Asp Arg Ile Ala Ile Ile Ser His Gly Lys Leu 1185 1190 1195 1200 Lys Cys Cys Gly Ser Pro Leu Phe Leu Lys Gly Thr Tyr Gly Asp Gly 1205 1210 1215 Tyr Arg Leu Thr Leu Val Lys Arg Pro Ala Glu Pro Gly Gly Pro Gln 1220 1225 1230 Glu Pro Gly Leu Ala Ser Ser Pro Pro Gly Arg Ala Pro Leu Ser Ser 1235 1240 1245 Cys Ser Glu Leu Gln Val Ser Gln Phe Ile Arg Lys His Val Ala Ser 1250 1255 1260 Cys Leu Leu Val Ser Asp Thr Ser Thr Glu Leu Ser Tyr Ile Leu Pro 1265 1270 1275 1280 Ser Glu Ala Ala Lys Lys Gly Ala Phe Glu Arg Leu Phe Gln His Leu 1285 1290 1295 Glu Arg Ser Leu Asp Ala Leu His Leu Ser Ser Phe Gly Leu Met Asp 1300 1305 1310 Thr Thr Leu Glu Glu Val Phe Leu Lys Val Ser Glu Glu Asp Gln Ser 1315 1320 1325 Leu Glu Asn Ser Glu Ala Asp Val Lys Glu Ser Arg Lys Asp Val Leu 1330 1335 1340 Pro Gly Ala Glu Gly Pro Ala Ser Gly Glu Gly His Ala Gly Asn Leu 1345 1350 1355 1360 Ala Arg Cys Ser Glu Leu Thr Gln Ser Gln Ala Ser Leu Gln Ser Ala 1365 1370 1375 Ser Ser Val Gly Ser Ala Arg Gly Asp Glu Gly Ala Gly Tyr Thr Asp 1380 1385 1390 Val Tyr Gly Asp Tyr Arg Pro Leu Phe Asp Asn Pro Gln Asp Pro Asp 1395 1400 1405 Asn Val Ser Leu Gln Glu Val Glu Ala Glu Ala Leu Ser Arg Val Gly 1410 1415 1420 Gln Gly Ser Arg Lys Leu Asp Gly Gly Trp Leu Lys Val Arg Gln Phe 1425 1430 1435 1440 His Gly Leu Leu Val Lys Arg Phe His Cys Ala Arg Arg Asn Ser Lys 1445 1450 1455 Ala Leu Phe Ser Gln Ile Leu Leu Pro Ala Phe Phe Val Cys Val Ala 1460 1465 1470 Met Thr Val Ala Leu Ser Val Pro Glu Ile Gly Asp Leu Pro Pro Leu 1475 1480 1485 Val Leu Ser Pro Ser Gln Tyr His Asn Tyr Thr Gln Pro Arg Gly Asn 1490 1495 1500 Phe Ile Pro Tyr Ala Asn Glu Glu Arg Arg Glu Tyr Arg Leu Arg Leu 1505 1510 1515 1520 Ser Pro Asp Ala Ser Pro Gln Gln Leu Val Ser Thr Phe Arg Leu Pro 1525 1530 1535 Ser Gly Val Gly Ala Thr Cys Val Leu Lys Ser Pro Ala Asn Gly Ser 1540 1545 1550 Leu Gly Pro Thr Leu Asn Leu Ser Ser Gly Glu Ser Arg Leu Leu Ala 1555 1560 1565 Ala Arg Phe Phe Asp Ser Met Cys Leu Glu Ser Phe Thr Gln Gly Leu 1570 1575 1580 Pro Leu Ser Asn Phe Val Pro Pro Pro Pro Ser Pro Ala Pro Ser Asp 1585 1590 1595 1600 Ser Pro Ala Ser Pro Asp Glu Asp Leu Gln Ala Trp Asn Val Ser Leu 1605 1610 1615 Pro Pro Thr Ala Gly Pro Glu Met Trp Thr Ser Ala Pro Ser Leu Pro 1620 1625 1630 Arg Leu Val Arg Glu Pro Val Arg Cys Thr Cys Ser Ala Gln Gly Thr 1635 1640 1645 Gly Phe Ser Cys Pro Ser Ser Val Gly Gly His Pro Pro Gln Met Arg 1650 1655 1660 Val Val Thr Gly Asp Ile Leu Thr Asp Ile Thr Gly His Asn Val Ser 1665 1670 1675 1680 Glu Tyr Leu Leu Phe Thr Ser Asp Arg Phe Arg Leu His Arg Tyr Gly 1685 1690 1695 Ala Ile Thr Phe Gly Asn Val Leu Lys Ser Ile Pro Ala Ser Phe Gly 1700 1705 1710 Thr Arg Ala Pro Pro Met Val Arg Lys Ile Ala Val Arg Arg Ala Ala 1715 1720 1725 Gln Val Phe Tyr Asn Asn Lys Gly Tyr His Ser Met Pro Thr Tyr Leu 1730 1735 1740 Asn Ser Leu Asn Asn Ala Ile Leu Arg Ala Asn Leu Pro Lys Ser Lys 1745 1750 1755 1760 Gly Asn Pro Ala Ala Tyr Gly Ile Thr Val Thr Asn His Pro Met Asn 1765 1770 1775 Lys Thr Ser Ala Ser Leu Ser Leu Asp Tyr Leu Leu Gln Gly Thr Asp 1780 1785 1790 Val Val Ile Ala Ile Phe Ile Ile Val Ala Met Ser Phe Val Pro Ala 1795 1800 1805 Ser Phe Val Val Phe Leu Val Ala Glu Lys Ser Thr Lys Ala Lys His 1810 1815 1820 Leu Gln Phe Val Ser Gly Cys Asn Pro Ile Ile Tyr Trp Leu Ala Asn 1825 1830 1835 1840 Tyr Val Trp Asp Met Leu Asn Tyr Leu Val Pro Ala Thr Cys Cys Val 1845 1850 1855 Ile Ile Leu Phe Val Phe Asp Leu Pro Ala Tyr Thr Ser Pro Thr Asn 1860 1865 1870 Phe Pro Ala Val Leu Ser Leu Phe Leu Leu Tyr Gly Trp Ser Ile Thr 1875 1880 1885 Pro Ile Met Tyr Pro Ala Ser Phe Trp Phe Glu Val Pro Ser Ser Ala 1890 1895 1900 Tyr Val Phe Leu Ile Val Ile Asn Leu Phe Ile Gly Ile Thr Ala Thr 1905 1910 1915 1920 Val Ala Thr Phe Leu Leu Gln Leu Phe Glu His Asp Lys Asp Leu Lys 1925 1930 1935 Val Val Asn Ser Tyr Leu Lys Ser Cys Phe Leu Ile Phe Pro Asn Tyr 1940 1945 1950 Asn Leu Gly His Gly Leu Met Glu Met Ala Tyr Asn Glu Tyr Ile Asn 1955 1960 1965 Glu Tyr Tyr Ala Lys Ile Gly Gln Phe Asp Lys Met Lys Ser Pro Phe 1970 1975 1980 Glu Trp Asp Ile Val Thr Arg Gly Leu Val Ala Met Ala Val Glu Gly 1985 1990 1995 2000 Val Val Gly Phe Leu Leu Thr Ile Met Cys Gln Tyr Asn Phe Leu Arg 2005 2010 2015 Arg Pro Gln Arg Met Pro Val Ser Thr Lys Pro Val Glu Asp Asp Val 2020 2025 2030 Asp Val Ala Ser Glu Arg Gln Arg Val Leu Arg Gly Asp Ala Asp Asn 2035 2040 2045 Asp Met Val Lys Ile Glu Asn Leu Thr Lys Val Tyr Lys Ser Arg Lys 2050 2055 2060 Ile Gly Arg Ile Leu Ala Val Asp Arg Leu Cys Leu Gly Val Arg Pro 2065 2070 2075 2080 Gly Glu Cys Phe Gly Leu Leu Gly Val Asn Gly Ala Gly Lys Thr Ser 2085 2090 2095 Thr Phe Lys Met Leu Thr Gly Asp Glu Ser Thr Thr Gly Gly Glu Ala 2100 2105 2110 Phe Val Asn Gly His Ser Val Leu Lys Glu Leu Leu Gln Val Gln Gln 2115 2120 2125 Ser Leu Gly Tyr Cys Pro Gln Cys Asp Ala Leu Phe Asp Glu Leu Thr 2130 2135 2140 Ala Arg Glu His Leu Gln Leu Tyr Thr Arg Leu Arg Gly Ile Ser Trp 2145 2150 2155 2160 Lys Asp Glu Ala Arg Val Val Lys Trp Ala Leu Glu Lys Leu Glu Leu 2165 2170 2175 Thr Lys Tyr Ala Asp Lys Pro Ala Gly Thr Tyr Ser Gly Gly Asn Lys 2180 2185 2190 Arg Lys Leu Ser Thr Ala Ile Ala Leu Ile Gly Tyr Pro Ala Phe Ile 2195 2200 2205 Phe Leu Asp Glu Pro Thr Thr Gly Met Asp Pro Lys Ala Arg Arg Phe 2210 2215 2220 Leu Trp Asn Leu Ile Leu Asp Leu Ile Lys Thr Gly Arg Ser Val Val 2225 2230 2235 2240 Leu Thr Ser His Ser Met Glu Glu Cys Glu Ala Leu Cys Thr Arg Leu 2245 2250 2255 Ala Ile Met Val Asn Gly Arg Leu Arg Cys Leu Gly Ser Ile Gln His 2260 2265 2270 Leu Lys Asn Arg Phe Gly Asp Gly Tyr Met Ile Thr Val Arg Thr Lys 2275 2280 2285 Ser Ser Gln Ser Val Lys Asp Val Val Arg Phe Phe Asn Arg Asn Phe 2290 2295 2300 Pro Glu Ala Met Leu Lys Glu Arg His His Thr Lys Val Gln Tyr Gln 2305 2310 2315 2320 Leu Lys Ser Glu His Ile Ser Leu Ala Gln Val Phe Ser Lys Met Glu 2325 2330 2335 Gln Val Ser Gly Val Leu Gly Ile Glu Asp Tyr Ser Val Ser Gln Thr 2340 2345 2350 Thr Leu Asp Asn Val Phe Val Asn Phe Ala Lys Lys Gln Ser Asp Asn 2355 2360 2365 Leu Glu Gln Gln Glu Thr Glu Pro Pro Ser Ala Leu Gln Ser Pro Leu 2370 2375 2380 Gly Cys Leu Leu Ser Leu Leu Arg Pro Arg Ser Ala Pro Thr Glu Leu 2385 2390 2395 2400 Arg Ala Leu Val Ala Asp Glu Pro Glu Asp Leu Asp Thr Glu Asp Glu 2405 2410 2415 Gly Leu Ile Ser Phe Glu Glu Glu Arg Ala Gln Leu Ser Phe Asn Thr 2420 2425 2430 Asp Thr Leu Cys 2435 <210> 84 <211> 532 <212> PRT <213> Homo sapiens <400> 84 Met Pro Gln Leu Tyr Ile Tyr Ile Arg Leu Leu Gly Ala Tyr Leu Phe 1 5 10 15 Ile Ile Ser Arg Val Gln Gly Gln Asn Leu Asp Ser Met Leu His Gly 20 25 30 Thr Gly Met Lys Ser Asp Ser Asp Gln Lys Lys Ser Glu Asn Gly Val 35 40 45 Thr Leu Ala Pro Glu Asp Thr Leu Pro Phe Leu Lys Cys Tyr Cys Ser 50 55 60 Gly His Cys Pro Asp Asp Ala Ile Asn Asn Thr Cys Ile Thr Asn Gly 65 70 75 80 His Cys Phe Ala Ile Ile Glu Glu Asp Asp Gln Gly Glu Thr Thr Leu 85 90 95 Ala Ser Gly Cys Met Lys Tyr Glu Gly Ser Asp Phe Gln Cys Lys Asp 100 105 110 Ser Pro Lys Ala Gln Leu Arg Arg Thr Ile Glu Cys Cys Arg Thr Asn 115 120 125 Leu Cys Asn Gln Tyr Leu Gln Pro Thr Leu Pro Pro Val Val Ile Gly 130 135 140 Pro Phe Phe Asp Gly Ser Ile Arg Trp Leu Val Leu Leu Ile Ser Met 145 150 155 160 Ala Val Cys Ile Ile Ala Met Ile Ile Phe Ser Ser Cys Phe Cys Tyr 165 170 175 Lys His Tyr Cys Lys Ser Ile Ser Ser Arg Arg Arg Tyr Asn Arg Asp 180 185 190 Leu Glu Gln Asp Glu Ala Phe Ile Pro Val Gly Glu Ser Leu Lys Asp 195 200 205 Leu Ile Asp Gln Ser Gln Ser Ser Gly Ser Gly Ser Gly Leu Pro Leu 210 215 220 Leu Val Gln Arg Thr Ile Ala Lys Gln Ile Gln Met Val Arg Gln Val 225 230 235 240 Gly Lys Gly Arg Tyr Gly Glu Val Trp Met Gly Lys Trp Arg Gly Glu 245 250 255 Lys Val Ala Val Lys Val Phe Phe Thr Thr Glu Glu Ala Ser Trp Phe 260 265 270 Arg Glu Thr Glu Ile Tyr Gln Thr Val Leu Met Arg His Glu Asn Ile 275 280 285 Leu Gly Phe Ile Ala Ala Asp Ile Lys Gly Thr Gly Ser Trp Thr Gln 290 295 300 Leu Tyr Leu Ile Thr Asp Tyr His Glu Asn Gly Ser Leu Tyr Asp Phe 305 310 315 320 Leu Lys Cys Ala Thr Leu Asp Thr Arg Ala Leu Leu Lys Leu Ala Tyr 325 330 335 Ser Ala Ala Cys Gly Leu Cys His Leu His Thr Glu Ile Tyr Gly Thr 340 345 350 Gln Gly Lys Pro Ala Ile Ala His Arg Asp Leu Lys Ser Lys Asn Ile 355 360 365 Leu Ile Lys Lys Asn Gly Ser Cys Cys Ile Ala Asp Leu Gly Leu Ala 370 375 380 Val Lys Phe Asn Ser Asp Thr Asn Glu Val Asp Val Pro Leu Asn Thr 385 390 395 400 Arg Val Gly Thr Lys Arg Tyr Met Ala Pro Glu Val Leu Asp Glu Ser 405 410 415 Leu Asn Lys Asn His Phe Gln Pro Tyr Ile Met Ala Asp Ile Tyr Ser 420 425 430 Phe Gly Leu Ile Ile Trp Glu Met Ala Arg Arg Cys Ile Thr Gly Gly 435 440 445 Ile Val Glu Glu Tyr Gln Leu Pro Tyr Tyr Asn Met Val Pro Ser Asp 450 455 460 Pro Ser Tyr Glu Asp Met Arg Glu Val Val Cys Val Lys Arg Leu Arg 465 470 475 480 Pro Ile Val Ser Asn Arg Trp Asn Ser Asp Glu Cys Leu Arg Ala Val 485 490 495 Leu Lys Leu Met Ser Glu Cys Trp Ala His Asn Pro Ala Ser Arg Leu 500 505 510 Thr Ala Leu Arg Ile Lys Lys Thr Leu Ala Lys Met Val Glu Ser Gln 515 520 525 Asp Val Lys Ile 530 <210> 85 <211> 133 <212> PRT <213> Homo sapiens <400> 85 Met Glu Thr Asn Ile Asn Trp Gly Ala Arg Val Phe Leu Ala Asp Phe 1 5 10 15 Gln Ala Gln Lys Val Ile Thr Asn Pro Ala Gly Lys Gly Leu Gly Glu 20 25 30 Val Leu Lys Val Lys Thr Thr Ala Val Asn Phe Gln His Lys Gly Ile 35 40 45 Pro Pro Lys Asn His Leu Gly Ala Leu Leu Asn Leu Tyr Cys Phe Phe 50 55 60 Gln His Lys Asn Asn Phe Arg Gly Asp Trp Gly Phe Gln Ser Ser Leu 65 70 75 80 Ala Leu Thr Ala Ser Trp Glu Gln His Gly Ser Phe Pro Asn His Gly 85 90 95 Gly Val Asn Ala Gly Leu Trp Gly Lys Lys Ser Leu Met Gly Gly Asn 100 105 110 Lys Trp Ala Leu Ala Leu Gln Met Val Pro Ser Pro Pro Leu Thr Gly 115 120 125 Ile Leu Leu Ala Leu 130 <210> 86 <211> 3210 <212> PRT <213> Homo sapiens <400> 86 Met Ser Trp Ala Leu Glu Glu Trp Lys Glu Gly Leu Pro Thr Arg Thr 1 5 10 15 Leu Gln Lys Ile Gln Glu Leu Glu Gly Gln Leu Asp Lys Leu Lys Lys 20 25 30 Glu Lys Gln Gln Arg Gln Phe Gln Leu Asp Ser Leu Glu Ala Ala Pro 35 40 45 Gln Lys Gln Thr Gln Lys Val Glu Asn Glu Lys Thr Glu Gly Thr Asn 50 55 60 Leu Lys Arg Glu Asn Gln Arg Leu Met Glu Ile Cys Glu Ser Leu Glu 65 70 75 80 Lys Thr Lys Gln Lys Ile Ser His Glu Leu Gln Val Lys Glu Ser Gln 85 90 95 Val Asn Phe Gln Glu Gly Gln Leu Asn Ser Gly Lys Lys Gln Ile Glu 100 105 110 Lys Leu Glu Gln Glu Leu Lys Arg Cys Lys Ser Glu Leu Glu Arg Ser 115 120 125 Gln Gln Ala Ala Gln Ser Ala Asp Val Ser Leu Asn Pro Cys Asn Thr 130 135 140 Pro Gln Lys Ile Phe Thr Thr Pro Leu Thr Pro Ser Gln Tyr Tyr Ser 145 150 155 160 Gly Ser Lys Tyr Glu Asp Leu Lys Glu Lys Tyr Asn Lys Glu Val Glu 165 170 175 Glu Arg Lys Arg Leu Glu Ala Glu Val Lys Ala Leu Gln Ala Lys Lys 180 185 190 Ala Ser Gln Thr Leu Pro Gln Ala Thr Met Asn His Arg Asp Ile Ala 195 200 205 Arg His Gln Ala Ser Ser Ser Val Phe Ser Trp Gln Gln Glu Lys Thr 210 215 220 Pro Ser His Leu Ser Ser Asn Ser Gln Arg Thr Pro Ile Arg Arg Asp 225 230 235 240 Phe Ser Ala Ser Tyr Phe Ser Gly Glu Leu Glu Val Thr Pro Ser Arg 245 250 255 Ser Thr Leu Gln Ile Gly Lys Arg Asp Ala Asn Ser Ser Phe Phe Gly 260 265 270 Asn Ser Ser Ser Pro His Leu Leu Asp Gln Leu Lys Ala Gln Asn Gln 275 280 285 Glu Leu Arg Asn Lys Ile Asn Glu Leu Glu Leu Arg Leu Gln Gly His 290 295 300 Glu Lys Glu Met Lys Gly Gln Val Asn Lys Phe Gln Glu Leu Gln Leu 305 310 315 320 Gln Leu Glu Lys Ala Lys Val Glu Leu Ile Glu Lys Glu Lys Val Leu 325 330 335 Asn Lys Cys Arg Asp Glu Leu Val Arg Thr Thr Ala Gln Tyr Asp Gln 340 345 350 Ala Ser Thr Lys Tyr Thr Ala Leu Glu Gln Lys Leu Lys Lys Leu Thr 355 360 365 Glu Asp Leu Ser Cys Gln Arg Gln Asn Ala Glu Ser Ala Arg Cys Ser 370 375 380 Leu Glu Gln Lys Ile Lys Glu Lys Glu Lys Glu Phe Gln Glu Glu Leu 385 390 395 400 Ser Arg Gln Gln Arg Ser Phe Gln Thr Leu Asp Gln Glu Cys Ile Gln 405 410 415 Met Lys Ala Arg Leu Thr Gln Glu Leu Gln Gln Ala Lys Asn Met His 420 425 430 Asn Val Leu Gln Ala Glu Leu Asp Lys Leu Thr Ser Val Lys Gln Gln 435 440 445 Leu Glu Asn Asn Leu Glu Glu Phe Lys Gln Lys Leu Cys Arg Ala Glu 450 455 460 Gln Ala Phe Gln Ala Ser Gln Ile Lys Glu Asn Glu Leu Arg Arg Ser 465 470 475 480 Met Glu Glu Met Lys Lys Glu Asn Asn Leu Leu Lys Ser His Ser Glu 485 490 495 Gln Lys Ala Arg Glu Val Cys His Leu Glu Ala Glu Leu Lys Asn Ile 500 505 510 Lys Gln Cys Leu Asn Gln Ser Gln Asn Phe Ala Glu Glu Met Lys Ala 515 520 525 Lys Asn Thr Ser Gln Glu Thr Met Leu Arg Asp Leu Gln Glu Lys Ile 530 535 540 Asn Gln Gln Glu Asn Ser Leu Thr Leu Glu Lys Leu Lys Leu Ala Val 545 550 555 560 Ala Asp Leu Glu Lys Gln Arg Asp Cys Ser Gln Asp Leu Leu Lys Lys 565 570 575 Arg Glu His His Ile Glu Gln Leu Asn Asp Lys Leu Ser Lys Thr Glu 580 585 590 Lys Glu Ser Lys Ala Leu Leu Ser Ala Leu Glu Leu Lys Lys Lys Glu 595 600 605 Tyr Glu Glu Leu Lys Glu Glu Lys Thr Leu Phe Ser Cys Trp Lys Ser 610 615 620 Glu Asn Glu Lys Leu Leu Thr Gln Met Glu Ser Glu Lys Glu Asn Leu 625 630 635 640 Gln Ser Lys Ile Asn His Leu Glu Thr Cys Leu Lys Thr Gln Gln Ile 645 650 655 Lys Ser His Glu Tyr Asn Glu Arg Val Arg Thr Leu Glu Met Asp Arg 660 665 670 Glu Asn Leu Ser Val Glu Ile Arg Asn Leu His Asn Val Leu Asp Ser 675 680 685 Lys Ser Val Glu Val Glu Thr Gln Lys Leu Ala Tyr Met Glu Leu Gln 690 695 700 Gln Lys Ala Glu Phe Ser Asp Gln Lys His Gln Lys Glu Ile Glu Asn 705 710 715 720 Met Cys Leu Lys Thr Ser Gln Leu Thr Gly Gln Val Glu Asp Leu Glu 725 730 735 His Lys Leu Gln Leu Leu Ser Asn Glu Ile Met Asp Lys Asp Arg Cys 740 745 750 Tyr Gln Asp Leu His Ala Glu Tyr Glu Ser Leu Arg Asp Leu Leu Lys 755 760 765 Ser Lys Asp Ala Ser Leu Val Thr Asn Glu Asp His Gln Arg Ser Leu 770 775 780 Leu Ala Phe Asp Gln Gln Pro Ala Met His His Ser Phe Ala Asn Ile 785 790 795 800 Ile Gly Glu Gln Gly Ser Met Pro Ser Glu Arg Ser Glu Cys Arg Leu 805 810 815 Glu Ala Asp Gln Ser Pro Lys Asn Ser Ala Ile Leu Gln Asn Arg Val 820 825 830 Asp Ser Leu Glu Phe Ser Leu Glu Ser Gln Lys Gln Met Asn Ser Asp 835 840 845 Leu Gln Lys Gln Cys Glu Glu Leu Val Gln Ile Lys Gly Glu Ile Glu 850 855 860 Glu Asn Leu Met Lys Ala Glu Gln Met His Gln Ser Phe Val Ala Glu 865 870 875 880 Thr Ser Gln Arg Ile Ser Lys Leu Gln Glu Asp Thr Ser Ala His Gln 885 890 895 Asn Val Val Ala Glu Thr Leu Ser Ala Leu Glu Asn Lys Glu Lys Glu 900 905 910 Leu Gln Leu Leu Asn Asp Lys Val Glu Thr Glu Gln Ala Glu Ile Gln 915 920 925 Glu Leu Lys Lys Ser Asn His Leu Leu Glu Asp Ser Leu Lys Glu Leu 930 935 940 Gln Leu Leu Ser Glu Thr Leu Ser Leu Glu Lys Lys Glu Met Ser Ser 945 950 955 960 Ile Ile Ser Leu Asn Lys Arg Glu Ile Glu Glu Leu Thr Gln Glu Asn 965 970 975 Gly Thr Leu Lys Glu Ile Asn Ala Ser Leu Asn Gln Glu Lys Met Asn 980 985 990 Leu Ile Gln Lys Ser Glu Ser Phe Ala Asn Tyr Ile Asp Glu Arg Glu 995 1000 1005 Lys Ser Ile Ser Glu Leu Ser Asp Gln Tyr Lys Gln Glu Lys Leu Ile 1010 1015 1020 Leu Leu Gln Arg Cys Glu Glu Thr Gly Asn Ala Tyr Glu Asp Leu Ser 1025 1030 1035 1040 Gln Lys Tyr Lys Ala Ala Gln Glu Lys Asn Ser Lys Leu Glu Cys Leu 1045 1050 1055 Leu Asn Glu Cys Thr Ser Leu Cys Glu Asn Arg Lys Asn Glu Leu Glu 1060 1065 1070 Gln Leu Lys Glu Ala Phe Ala Lys Glu His Gln Glu Phe Leu Thr Lys 1075 1080 1085 Leu Ala Phe Ala Glu Glu Arg Asn Gln Asn Leu Met Leu Glu Leu Glu 1090 1095 1100 Thr Val Gln Gln Ala Leu Arg Ser Glu Met Thr Asp Asn Gln Asn Asn 1105 1110 1115 1120 Ser Lys Ser Glu Ala Gly Gly Leu Lys Gln Glu Ile Met Thr Leu Lys 1125 1130 1135 Glu Glu Gln Asn Lys Met Gln Lys Glu Val Asn Asp Leu Leu Gln Glu 1140 1145 1150 Asn Glu Gln Leu Met Lys Val Met Lys Thr Lys His Glu Cys Gln Asn 1155 1160 1165 Leu Glu Ser Glu Pro Ile Arg Asn Ser Val Lys Glu Arg Glu Ser Glu 1170 1175 1180 Arg Asn Gln Cys Asn Phe Lys Pro Gln Met Asp Leu Glu Val Lys Glu 1185 1190 1195 1200 Ile Ser Leu Asp Ser Tyr Asn Ala Gln Leu Val Gln Leu Glu Ala Met 1205 1210 1215 Leu Arg Asn Lys Glu Leu Lys Leu Gln Glu Ser Glu Lys Glu Lys Glu 1220 1225 1230 Cys Leu Gln His Glu Leu Gln Thr Ile Arg Gly Asp Leu Glu Thr Ser 1235 1240 1245 Asn Leu Gln Asp Met Gln Ser Gln Glu Ile Ser Gly Leu Lys Asp Cys 1250 1255 1260 Glu Ile Asp Ala Glu Glu Lys Tyr Ile Ser Gly Pro His Glu Leu Ser 1265 1270 1275 1280 Thr Ser Gln Asn Asp Asn Ala His Leu Gln Cys Ser Leu Gln Thr Thr 1285 1290 1295 Met Asn Lys Leu Asn Glu Leu Glu Lys Ile Cys Glu Ile Leu Gln Ala 1300 1305 1310 Glu Lys Tyr Glu Leu Val Thr Glu Leu Asn Asp Ser Arg Ser Glu Cys 1315 1320 1325 Ile Thr Ala Thr Arg Lys Met Ala Glu Glu Val Gly Lys Leu Leu Asn 1330 1335 1340 Glu Val Lys Ile Leu Asn Asp Asp Ser Gly Leu Leu His Gly Glu Leu 1345 1350 1355 1360 Val Glu Asp Ile Pro Gly Gly Glu Phe Gly Glu Gln Pro Asn Glu Gln 1365 1370 1375 His Pro Val Ser Leu Ala Pro Leu Asp Glu Ser Asn Ser Tyr Glu His 1380 1385 1390 Leu Thr Leu Ser Asp Lys Glu Val Gln Met His Phe Ala Glu Leu Gln 1395 1400 1405 Glu Lys Phe Leu Ser Leu Gln Ser Glu His Lys Ile Leu His Asp Gln 1410 1415 1420 His Cys Gln Met Ser Ser Lys Met Ser Glu Leu Gln Thr Tyr Val Asp 1425 1430 1435 1440 Ser Leu Lys Ala Glu Asn Leu Val Leu Ser Thr Asn Leu Arg Asn Phe 1445 1450 1455 Gln Gly Asp Leu Val Lys Glu Met Gln Leu Gly Leu Glu Glu Gly Leu 1460 1465 1470 Val Pro Ser Leu Ser Ser Ser Cys Val Pro Asp Ser Ser Ser Leu Ser 1475 1480 1485 Ser Leu Gly Asp Ser Ser Phe Tyr Arg Ala Leu Leu Glu Gln Thr Gly 1490 1495 1500 Asp Met Ser Leu Leu Ser Asn Leu Glu Gly Ala Val Ser Ala Asn Gln 1505 1510 1515 1520 Cys Ser Val Asp Glu Val Phe Cys Ser Ser Leu Gln Thr Tyr Val Asp 1525 1530 1535 Ser Leu Lys Ala Glu Asn Leu Val Leu Ser Thr Asn Leu Arg Asn Phe 1540 1545 1550 Gln Gly Asp Leu Val Lys Glu Met Gln Leu Gly Leu Glu Glu Gly Leu 1555 1560 1565 Val Pro Ser Leu Ser Ser Ser Cys Val Pro Asp Ser Ser Ser Leu Ser 1570 1575 1580 Ser Leu Gly Asp Ser Ser Phe Tyr Arg Ala Leu Leu Glu Gln Thr Gly 1585 1590 1595 1600 Asp Met Ser Leu Leu Ser Asn Leu Glu Gly Val Val Ser Ala Asn Gln 1605 1610 1615 Cys Ser Val Asp Glu Val Phe Cys Ser Ser Leu Gln Glu Glu Asn Leu 1620 1625 1630 Thr Arg Lys Glu Thr Pro Ser Ala Pro Ala Lys Gly Val Glu Glu Leu 1635 1640 1645 Glu Ser Leu Cys Glu Val Tyr Arg Gln Ser Leu Glu Lys Leu Glu Glu 1650 1655 1660 Lys Met Glu Ser Gln Gly Ile Met Lys Asn Lys Glu Ile Gln Glu Leu 1665 1670 1675 1680 Glu Gln Leu Leu Ser Ser Glu Arg Gln Glu Leu Asp Cys Leu Arg Lys 1685 1690 1695 Gln Tyr Leu Ser Glu Asn Glu Gln Trp Gln Gln Lys Leu Thr Ser Val 1700 1705 1710 Thr Leu Glu Met Glu Ser Lys Leu Ala Ala Glu Lys Lys Gln Thr Glu 1715 1720 1725 Gln Leu Ser Leu Glu Leu Glu Val Ala Arg Leu Gln Leu Gln Gly Leu 1730 1735 1740 Asp Leu Ser Ser Arg Ser Leu Leu Gly Ile Asp Thr Glu Asp Ala Ile 1745 1750 1755 1760 Gln Gly Arg Asn Glu Ser Cys Asp Ile Ser Lys Glu His Thr Ser Glu 1765 1770 1775 Thr Thr Glu Arg Thr Pro Lys His Asp Val His Gln Ile Cys Asp Lys 1780 1785 1790 Asp Ala Gln Gln Asp Leu Asn Leu Asp Ile Glu Lys Ile Thr Glu Thr 1795 1800 1805 Gly Ala Val Lys Pro Thr Gly Glu Cys Ser Gly Glu Gln Ser Pro Asp 1810 1815 1820 Thr Asn Tyr Glu Pro Pro Gly Glu Asp Lys Thr Gln Gly Ser Ser Glu 1825 1830 1835 1840 Cys Ile Ser Glu Leu Ser Phe Ser Gly Pro Asn Ala Leu Val Pro Met 1845 1850 1855 Asp Phe Leu Gly Asn Gln Glu Asp Ile His Asn Leu Gln Leu Arg Val 1860 1865 1870 Lys Glu Thr Ser Asn Glu Asn Leu Arg Leu Leu His Val Ile Glu Asp 1875 1880 1885 Arg Asp Arg Lys Val Glu Ser Leu Leu Asn Glu Met Lys Glu Leu Asp 1890 1895 1900 Ser Lys Leu His Leu Gln Glu Val Gln Leu Met Thr Lys Ile Glu Ala 1905 1910 1915 1920 Cys Ile Glu Leu Glu Lys Ile Val Gly Glu Leu Lys Lys Glu Asn Ser 1925 1930 1935 Asp Leu Ser Glu Lys Leu Glu Tyr Phe Ser Cys Asp His Gln Glu Leu 1940 1945 1950 Leu Gln Arg Val Glu Thr Ser Glu Gly Leu Asn Ser Asp Leu Glu Met 1955 1960 1965 His Ala Asp Lys Ser Ser Arg Glu Asp Ile Gly Asp Asn Val Ala Lys 1970 1975 1980 Val Asn Asp Ser Trp Lys Glu Arg Phe Leu Asp Val Glu Asn Glu Leu 1985 1990 1995 2000 Ser Arg Ile Arg Ser Glu Lys Ala Ser Ile Glu His Glu Ala Leu Tyr 2005 2010 2015 Leu Glu Ala Asp Leu Glu Val Val Gln Thr Glu Lys Leu Cys Leu Glu 2020 2025 2030 Lys Asp Asn Glu Asn Lys Gln Lys Val Ile Val Cys Leu Glu Glu Glu 2035 2040 2045 Leu Ser Val Val Thr Ser Glu Arg Asn Gln Leu Arg Gly Glu Leu Asp 2050 2055 2060 Thr Met Ser Lys Lys Thr Thr Ala Leu Asp Gln Leu Ser Glu Lys Met 2065 2070 2075 2080 Lys Glu Lys Thr Gln Glu Leu Glu Ser His Gln Ser Glu Cys Leu His 2085 2090 2095 Cys Ile Gln Val Ala Glu Ala Glu Val Lys Glu Lys Thr Glu Leu Leu 2100 2105 2110 Gln Thr Leu Ser Ser Asp Val Ser Glu Leu Leu Lys Asp Lys Thr His 2115 2120 2125 Leu Gln Glu Lys Leu Gln Ser Leu Glu Lys Asp Ser Gln Ala Leu Ser 2130 2135 2140 Leu Thr Lys Cys Glu Leu Glu Asn Gln Ile Ala Gln Leu Asn Lys Glu 2145 2150 2155 2160 Lys Glu Leu Leu Val Lys Glu Ser Glu Ser Leu Gln Ala Arg Leu Ser 2165 2170 2175 Glu Ser Asp Tyr Glu Lys Leu Asn Val Ser Lys Ala Leu Glu Ala Ala 2180 2185 2190 Leu Val Glu Lys Gly Glu Phe Ala Leu Arg Leu Ser Ser Thr Gln Glu 2195 2200 2205 Glu Val His Gln Leu Arg Arg Gly Ile Glu Lys Leu Arg Val Arg Ile 2210 2215 2220 Glu Ala Asp Glu Lys Lys Gln Leu His Ile Ala Glu Lys Leu Lys Glu 2225 2230 2235 2240 Arg Glu Arg Glu Asn Asp Ser Leu Lys Asp Lys Val Glu Asn Leu Glu 2245 2250 2255 Arg Glu Leu Gln Met Ser Glu Glu Asn Gln Glu Leu Val Ile Leu Asp 2260 2265 2270 Ala Glu Asn Ser Lys Ala Glu Val Glu Thr Leu Lys Thr Gln Ile Glu 2275 2280 2285 Glu Met Ala Arg Ser Leu Lys Val Phe Glu Leu Asp Leu Val Thr Leu 2290 2295 2300 Arg Ser Glu Lys Glu Asn Leu Thr Lys Gln Ile Gln Glu Lys Gln Gly 2305 2310 2315 2320 Gln Leu Ser Glu Leu Asp Lys Leu Leu Ser Ser Phe Lys Ser Leu Leu 2325 2330 2335 Glu Glu Lys Glu Gln Ala Glu Ile Gln Ile Lys Glu Glu Ser Lys Thr 2340 2345 2350 Ala Val Glu Met Leu Gln Asn Gln Leu Lys Glu Leu Asn Glu Ala Val 2355 2360 2365 Ala Ala Leu Cys Gly Asp Gln Glu Ile Met Lys Ala Thr Glu Gln Ser 2370 2375 2380 Leu Asp Pro Pro Ile Glu Glu Glu His Gln Leu Arg Asn Ser Ile Glu 2385 2390 2395 2400 Lys Leu Arg Ala Arg Leu Glu Ala Asp Glu Lys Lys Gln Leu Cys Val 2405 2410 2415 Leu Gln Gln Leu Lys Glu Ser Glu His His Ala Asp Leu Leu Lys Gly 2420 2425 2430 Arg Val Glu Asn Leu Glu Arg Glu Leu Glu Ile Ala Arg Thr Asn Gln 2435 2440 2445 Glu His Ala Ala Leu Glu Ala Glu Asn Ser Lys Gly Glu Val Glu Thr 2450 2455 2460 Leu Lys Ala Lys Ile Glu Gly Met Thr Gln Ser Leu Arg Gly Leu Glu 2465 2470 2475 2480 Leu Asp Val Val Thr Ile Arg Ser Glu Lys Glu Asp Leu Thr Asn Glu 2485 2490 2495 Leu Gln Lys Glu Gln Glu Arg Ile Ser Glu Leu Glu Ile Ile Asn Ser 2500 2505 2510 Ser Phe Glu Asn Ile Leu Gln Glu Lys Glu Gln Glu Lys Val Gln Met 2515 2520 2525 Lys Glu Lys Ser Ser Thr Ala Met Glu Met Leu Gln Thr Gln Leu Lys 2530 2535 2540 Glu Leu Asn Glu Arg Val Ala Ala Leu His Asn Asp Gln Glu Ala Cys 2545 2550 2555 2560 Lys Ala Lys Glu Gln Asn Leu Ser Ser Gln Val Glu Cys Leu Glu Leu 2565 2570 2575 Glu Lys Ala Gln Leu Leu Gln Gly Leu Asp Glu Ala Lys Asn Asn Tyr 2580 2585 2590 Ile Val Leu Gln Ser Ser Val Asn Gly Leu Ile Gln Glu Val Glu Asp 2595 2600 2605 Gly Lys Gln Lys Leu Glu Lys Lys Asp Glu Glu Ile Ser Arg Leu Lys 2610 2615 2620 Asn Gln Ile Gln Asp Gln Glu Gln Leu Val Ser Lys Leu Ser Gln Val 2625 2630 2635 2640 Glu Gly Glu His Gln Leu Trp Lys Glu Gln Asn Leu Glu Leu Arg Asn 2645 2650 2655 Leu Thr Val Glu Leu Glu Gln Lys Ile Gln Val Leu Gln Ser Lys Asn 2660 2665 2670 Ala Ser Leu Gln Asp Thr Leu Glu Val Leu Gln Ser Ser Tyr Lys Asn 2675 2680 2685 Leu Glu Asn Glu Leu Glu Leu Thr Lys Met Asp Lys Met Ser Phe Val 2690 2695 2700 Glu Lys Val Asn Lys Met Thr Ala Lys Glu Thr Glu Leu Gln Arg Glu 2705 2710 2715 2720 Met His Glu Met Ala Gln Lys Thr Ala Glu Leu Gln Glu Glu Leu Ser 2725 2730 2735 Gly Glu Lys Asn Arg Leu Ala Gly Glu Leu Gln Leu Leu Leu Glu Glu 2740 2745 2750 Ile Lys Ser Ser Lys Asp Gln Leu Lys Glu Leu Thr Leu Glu Asn Ser 2755 2760 2765 Glu Leu Lys Lys Ser Leu Asp Cys Met His Lys Asp Gln Val Glu Lys 2770 2775 2780 Glu Gly Lys Val Arg Glu Glu Ile Ala Glu Tyr Gln Leu Arg Leu His 2785 2790 2795 2800 Glu Ala Glu Lys Lys His Gln Ala Leu Leu Leu Asp Thr Asn Lys Gln 2805 2810 2815 Tyr Glu Val Glu Ile Gln Thr Tyr Arg Glu Lys Leu Thr Ser Lys Glu 2820 2825 2830 Glu Cys Leu Ser Ser Gln Lys Leu Glu Ile Asp Leu Leu Lys Ser Ser 2835 2840 2845 Lys Glu Glu Leu Asn Asn Ser Leu Lys Ala Thr Thr Gln Ile Leu Glu 2850 2855 2860 Glu Leu Lys Lys Thr Lys Met Asp Asn Leu Lys Tyr Val Asn Gln Leu 2865 2870 2875 2880 Lys Lys Glu Asn Glu Arg Ala Gln Gly Lys Met Lys Leu Leu Ile Lys 2885 2890 2895 Ser Cys Lys Gln Leu Glu Glu Glu Lys Glu Ile Leu Gln Lys Glu Leu 2900 2905 2910 Ser Gln Leu Gln Ala Ala Gln Glu Lys Gln Lys Thr Gly Thr Val Met 2915 2920 2925 Asp Thr Lys Val Asp Glu Leu Thr Thr Glu Ile Lys Glu Leu Lys Glu 2930 2935 2940 Thr Leu Glu Glu Lys Thr Lys Glu Ala Asp Glu Tyr Leu Asp Lys Tyr 2945 2950 2955 2960 Cys Ser Leu Leu Ile Ser His Glu Lys Leu Glu Lys Ala Lys Glu Met 2965 2970 2975 Leu Glu Thr Gln Val Ala His Leu Cys Ser Gln Gln Ser Lys Gln Asp 2980 2985 2990 Ser Arg Gly Ser Pro Leu Leu Gly Pro Val Val Pro Gly Pro Ser Pro 2995 3000 3005 Ile Pro Ser Val Thr Glu Lys Arg Leu Ser Ser Gly Gln Asn Lys Ala 3010 3015 3020 Ser Gly Lys Arg Gln Arg Ser Ser Gly Ile Trp Glu Asn Gly Gly Gly 3025 3030 3035 3040 Pro Thr Pro Ala Thr Pro Glu Ser Phe Ser Lys Lys Ser Lys Lys Ala 3045 3050 3055 Val Met Ser Gly Ile His Pro Ala Glu Asp Thr Glu Gly Thr Glu Phe 3060 3065 3070 Glu Pro Glu Gly Leu Pro Glu Val Val Lys Lys Gly Phe Ala Asp Ile 3075 3080 3085 Pro Thr Gly Lys Thr Ser Pro Tyr Ile Leu Arg Arg Thr Thr Met Ala 3090 3095 3100 Thr Arg Thr Ser Pro Arg Leu Ala Ala Gln Lys Leu Ala Leu Ser Pro 3105 3110 3115 3120 Leu Ser Leu Gly Lys Glu Asn Leu Ala Glu Ser Ser Lys Pro Thr Ala 3125 3130 3135 Gly Gly Ser Arg Ser Gln Lys Val Lys Val Ala Gln Arg Ser Pro Val 3140 3145 3150 Asp Ser Gly Thr Ile Leu Arg Glu Pro Thr Thr Lys Ser Val Pro Val 3155 3160 3165 Asn Asn Leu Pro Glu Arg Ser Pro Thr Asp Ser Pro Arg Glu Gly Leu 3170 3175 3180 Arg Val Lys Arg Gly Arg Leu Val Pro Ser Pro Lys Ala Gly Leu Glu 3185 3190 3195 3200 Ser Lys Gly Ser Glu Asn Cys Lys Val Gln 3205 3210 <210> 87 <211> 586 <212> PRT <213> Homo sapiens <400> 87 Met Gly Val Asn Ala Val His Trp Phe Arg Lys Gly Leu Arg Leu His 1 5 10 15 Asp Asn Pro Ala Leu Lys Glu Cys Ile Gln Gly Ala Asp Thr Ile Arg 20 25 30 Cys Val Tyr Ile Leu Asp Pro Trp Phe Ala Gly Ser Ser Asn Val Gly 35 40 45 Ile Asn Arg Trp Arg Phe Leu Leu Gln Cys Leu Glu Asp Leu Asp Ala 50 55 60 Asn Leu Arg Lys Leu Asn Ser Arg Leu Phe Val Ile Arg Gly Gln Pro 65 70 75 80 Ala Asp Val Phe Pro Arg Leu Phe Lys Glu Trp Asn Ile Thr Lys Leu 85 90 95 Ser Ile Glu Tyr Asp Ser Glu Pro Phe Gly Lys Glu Arg Asp Ala Ala 100 105 110 Ile Lys Lys Leu Ala Thr Glu Ala Gly Val Glu Val Ile Val Arg Ile 115 120 125 Ser His Thr Leu Tyr Asp Leu Asp Lys Ile Ile Glu Leu Asn Gly Gly 130 135 140 Gln Pro Pro Leu Thr Tyr Lys Arg Phe Gln Thr Leu Ile Ser Lys Met 145 150 155 160 Glu Pro Leu Glu Ile Pro Val Glu Thr Ile Thr Ser Glu Val Ile Glu 165 170 175 Lys Cys Thr Thr Pro Leu Ser Asp Asp His Asp Glu Lys Tyr Gly Val 180 185 190 Pro Ser Leu Glu Glu Leu Gly Phe Asp Thr Asp Gly Leu Ser Ser Ala 195 200 205 Val Trp Pro Gly Gly Glu Thr Glu Ala Leu Thr Arg Leu Glu Arg His 210 215 220 Leu Glu Arg Lys Ala Trp Val Ala Asn Phe Glu Arg Pro Arg Met Asn 225 230 235 240 Ala Asn Ser Leu Leu Ala Ser Pro Thr Gly Leu Ser Pro Tyr Leu Arg 245 250 255 Phe Gly Cys Leu Ser Cys Arg Leu Phe Tyr Phe Lys Leu Thr Asp Leu 260 265 270 Tyr Lys Lys Val Lys Lys Asn Ser Ser Pro Pro Leu Ser Leu Tyr Gly 275 280 285 Gln Leu Leu Trp Arg Glu Phe Phe Tyr Thr Ala Ala Thr Asn Asn Pro 290 295 300 Arg Phe Asp Lys Met Glu Gly Asn Pro Ile Cys Val Gln Ile Pro Trp 305 310 315 320 Asp Lys Asn Pro Glu Ala Leu Ala Lys Trp Ala Glu Gly Arg Thr Gly 325 330 335 Phe Pro Trp Ile Asp Ala Ile Met Thr Gln Leu Arg Gln Glu Gly Trp 340 345 350 Ile His His Leu Ala Arg His Ala Val Ala Cys Phe Leu Thr Arg Gly 355 360 365 Asp Leu Trp Ile Ser Trp Glu Glu Gly Met Lys Val Phe Glu Glu Leu 370 375 380 Leu Leu Asp Ala Asp Trp Ser Ile Asn Ala Gly Ser Trp Met Trp Leu 385 390 395 400 Ser Cys Ser Ser Phe Phe Gln Gln Phe Phe His Cys Tyr Cys Pro Val 405 410 415 Gly Phe Gly Arg Arg Thr Asp Pro Asn Gly Asp Tyr Ile Arg Arg Tyr 420 425 430 Leu Pro Val Leu Arg Gly Phe Pro Ala Lys Tyr Ile Tyr Asp Pro Trp 435 440 445 Asn Ala Pro Glu Gly Ile Gln Lys Val Ala Lys Cys Leu Ile Gly Val 450 455 460 Asn Tyr Pro Lys Pro Met Val Asn His Ala Glu Ala Ser Arg Leu Asn 465 470 475 480 Ile Glu Arg Met Lys Gln Ile Tyr Gln Gln Leu Ser Arg Tyr Arg Gly 485 490 495 Leu Gly Leu Leu Ala Ser Val Pro Ser Asn Pro Asn Gly Asn Gly Gly 500 505 510 Phe Met Gly Tyr Ser Ala Glu Asn Ile Pro Gly Cys Ser Ser Ser Gly 515 520 525 Ser Cys Ser Gln Gly Ser Gly Ile Leu His Tyr Ala His Gly Asp Ser 530 535 540 Gln Gln Thr His Leu Leu Lys Gln Gly Arg Ser Ser Met Gly Thr Gly 545 550 555 560 Leu Ser Gly Gly Lys Arg Pro Ser Gln Glu Glu Asp Thr Gln Ser Ile 565 570 575 Gly Pro Lys Val Gln Arg Gln Ser Thr Asn 580 585 <210> 88 <211> 675 <212> PRT <213> Homo sapiens <400> 88 Met Glu Gly Arg Pro Pro Pro Glu Gly Arg Pro Pro Pro Arg Pro Arg 1 5 10 15 Thr Gly Arg Ala Pro Arg Gly Arg Arg Arg Ala Val Phe Ala Ala Val 20 25 30 Leu His Trp Ser His Ile Thr His Leu Phe Glu Asn Asp Arg His Phe 35 40 45 Ser His Leu Ser Thr Leu Glu Arg Glu Met Ala Phe Arg Thr Glu Met 50 55 60 Gly Leu Tyr Tyr Ser Tyr Phe Lys Thr Ile Val Glu Ala Pro Ser Phe 65 70 75 80 Leu Asn Gly Val Trp Met Ile Met Asn Asp Lys Leu Thr Glu Tyr Pro 85 90 95 Leu Val Ile Asn Thr Leu Lys Arg Phe Asn Leu Tyr Pro Glu Val Ile 100 105 110 Leu Ala Ser Trp Tyr Arg Ile Tyr Thr Lys Ile Met Asp Leu Ile Gly 115 120 125 Ile Gln Thr Lys Ile Cys Trp Thr Val Thr Arg Gly Glu Gly Leu Ser 130 135 140 Pro Ile Glu Ser Cys Glu Gly Leu Gly Asp Pro Ala Cys Phe Tyr Val 145 150 155 160 Ala Val Ile Phe Ile Leu Asn Gly Leu Met Met Ala Leu Phe Phe Ile 165 170 175 Tyr Gly Thr Tyr Leu Ser Gly Ser Arg Leu Gly Gly Leu Val Thr Val 180 185 190 Leu Cys Phe Phe Phe Asn His Gly Glu Cys Thr Arg Val Met Trp Thr 195 200 205 Pro Pro Leu Arg Glu Ser Phe Ser Tyr Pro Phe Leu Val Leu Gln Met 210 215 220 Leu Leu Val Thr His Ile Leu Arg Ala Thr Lys Leu Tyr Arg Gly Ser 225 230 235 240 Leu Ile Ala Leu Cys Ile Ser Asn Val Phe Phe Met Leu Pro Trp Gln 245 250 255 Phe Ala Gln Phe Val Leu Leu Thr Gln Ile Ala Ser Leu Phe Ala Val 260 265 270 Tyr Val Val Gly Tyr Ile Asp Ile Cys Lys Leu Arg Lys Ile Ile Tyr 275 280 285 Ile His Met Ile Ser Leu Ala Leu Cys Phe Val Leu Met Phe Gly Asn 290 295 300 Ser Met Leu Leu Thr Ser Tyr Tyr Ala Ser Ser Leu Val Ile Ile Trp 305 310 315 320 Gly Ile Leu Ala Met Lys Pro His Phe Leu Lys Ile Asn Val Ser Glu 325 330 335 Leu Ser Leu Trp Val Ile Gln Gly Cys Phe Trp Leu Phe Gly Thr Val 340 345 350 Ile Leu Lys Tyr Leu Thr Ser Lys Ile Phe Gly Ile Ala Asp Asp Ala 355 360 365 His Ile Gly Asn Leu Leu Thr Ser Lys Phe Phe Ser Tyr Lys Asp Phe 370 375 380 Asp Thr Leu Leu Tyr Thr Cys Ala Ala Glu Phe Asp Phe Met Glu Lys 385 390 395 400 Glu Thr Pro Leu Arg Tyr Thr Lys Thr Leu Leu Leu Pro Val Val Leu 405 410 415 Val Val Phe Val Ala Ile Val Arg Lys Ile Ile Ser Asp Met Trp Gly 420 425 430 Val Leu Ala Lys Gln Gln Thr His Val Arg Lys His Gln Phe Asp His 435 440 445 Gly Glu Leu Val Tyr His Ala Leu Gln Leu Leu Ala Tyr Thr Ala Leu 450 455 460 Gly Ile Leu Ile Met Arg Leu Lys Leu Phe Leu Thr Pro His Met Cys 465 470 475 480 Val Met Ala Ser Leu Ile Cys Ser Arg Gln Leu Phe Gly Trp Leu Phe 485 490 495 Cys Lys Val His Pro Gly Ala Ile Val Phe Ala Ile Leu Ala Ala Met 500 505 510 Ser Ile Gln Gly Ser Ala Asn Leu Gln Thr Gln Trp Asn Ile Val Gly 515 520 525 Glu Phe Ser Asn Leu Pro Gln Glu Glu Leu Ile Glu Trp Ile Lys Tyr 530 535 540 Ser Thr Lys Pro Asp Ala Val Phe Ala Gly Ala Met Pro Thr Met Ala 545 550 555 560 Ser Val Lys Leu Ser Ala Leu Arg Pro Ile Val Asn His Pro His Tyr 565 570 575 Glu Asp Ala Gly Leu Arg Ala Arg Thr Lys Ile Val Tyr Ser Met Tyr 580 585 590 Ser Arg Lys Ala Ala Glu Glu Val Lys Arg Glu Leu Ile Lys Leu Lys 595 600 605 Val Asn Tyr Tyr Ile Leu Glu Glu Ser Trp Cys Val Arg Arg Ser Lys 610 615 620 Pro Gly Cys Ser Met Pro Glu Ile Trp Asp Val Glu Asp Pro Ala Asn 625 630 635 640 Ala Gly Lys Thr Pro Leu Cys Asn Leu Leu Val Lys Asp Ser Lys Pro 645 650 655 His Phe Thr Thr Val Phe Gln Asn Ser Val Tyr Lys Val Leu Glu Val 660 665 670 Val Lys Glu 675 <210> 89 <211> 725 <212> PRT <213> Homo sapiens <400> 89 Met Ala Met Ala Met Ser Asp Ser Gly Ala Ser Arg Leu Arg Arg Gln 1 5 10 15 Leu Glu Ser Gly Gly Phe Glu Ala Arg Leu Tyr Val Lys Gln Leu Ser 20 25 30 Gln Gln Ser Asp Gly Asp Arg Asp Leu Gln Glu His Arg Gln Arg Ile 35 40 45 Gln Ala Leu Ala Glu Glu Thr Ala Gln Asn Leu Lys Arg Asn Val Tyr 50 55 60 Gln Asn Tyr Arg Gln Phe Ile Glu Thr Ala Arg Glu Ile Ser Tyr Leu 65 70 75 80 Glu Ser Glu Met Tyr Gln Leu Ser His Leu Leu Thr Glu Gln Lys Ser 85 90 95 Ser Leu Glu Ser Ile Pro Leu Thr Leu Leu Pro Ala Ala Ala Ala Ala 100 105 110 Gly Ala Ala Ala Ala Ser Gly Gly Glu Glu Gly Val Gly Gly Ala Gly 115 120 125 Gly Arg Asp His Leu Arg Gly Gln Ala Gly Phe Phe Ser Thr Pro Gly 130 135 140 Gly Ala Ser Arg Asp Gly Ser Gly Pro Gly Glu Glu Gly Lys Gln Arg 145 150 155 160 Thr Leu Thr Thr Leu Leu Glu Lys Val Glu Gly Cys Arg His Leu Leu 165 170 175 Glu Thr Pro Gly Gln Tyr Leu Val Tyr Asn Gly Asp Leu Val Glu Tyr 180 185 190 Asp Ala Asp His Met Ala Gln Leu Gln Arg Val His Gly Phe Leu Met 195 200 205 Asn Asp Cys Leu Leu Val Ala Thr Trp Leu Pro Gln Arg Arg Gly Met 210 215 220 Tyr Arg Tyr Asn Ala Leu Tyr Ser Leu Asp Gly Leu Ala Val Val Asn 225 230 235 240 Val Lys Asp Asn Pro Pro Met Lys Asp Met Phe Lys Leu Leu Met Phe 245 250 255 Pro Glu Ser Arg Ile Phe Gln Ala Glu Asn Ala Lys Ile Lys Arg Glu 260 265 270 Trp Leu Glu Val Leu Glu Asp Thr Lys Arg Ala Leu Ser Glu Lys Arg 275 280 285 Arg Arg Glu Gln Glu Glu Ala Ala Ala Pro Arg Gly Pro Pro Gln Val 290 295 300 Thr Ser Lys Ala Thr Asn Pro Phe Glu Asp Asp Glu Glu Glu Glu Pro 305 310 315 320 Ala Val Pro Glu Val Glu Glu Glu Lys Val Asp Leu Ser Met Glu Trp 325 330 335 Ile Gln Glu Leu Pro Glu Asp Leu Asp Val Cys Ile Ala Gln Arg Asp 340 345 350 Phe Glu Gly Ala Val Asp Leu Leu Asp Lys Leu Asn His Tyr Leu Glu 355 360 365 Asp Lys Pro Ser Pro Pro Pro Val Lys Glu Leu Arg Ala Lys Val Glu 370 375 380 Glu Arg Val Arg Gln Leu Thr Glu Val Leu Val Phe Glu Leu Ser Pro 385 390 395 400 Asp Arg Ser Leu Arg Gly Gly Pro Lys Ala Thr Arg Arg Ala Val Ser 405 410 415 Gln Leu Ile Arg Leu Gly Gln Cys Thr Lys Ala Cys Glu Leu Phe Leu 420 425 430 Arg Asn Arg Ala Ala Ala Val His Thr Ala Ile Arg Gln Leu Arg Ile 435 440 445 Glu Gly Ala Thr Leu Leu Tyr Ile His Lys Leu Cys His Val Phe Phe 450 455 460 Thr Ser Leu Leu Glu Thr Ala Arg Glu Phe Glu Ile Asp Phe Ala Gly 465 470 475 480 Thr Asp Ser Gly Cys Tyr Ser Ala Phe Val Val Trp Ala Arg Ser Ala 485 490 495 Met Gly Met Phe Val Asp Ala Phe Ser Lys Gln Val Phe Asp Ser Lys 500 505 510 Glu Ser Leu Ser Thr Ala Ala Glu Cys Val Lys Val Ala Lys Glu His 515 520 525 Cys Gln Gln Leu Gly Asp Ile Gly Leu Asp Leu Thr Phe Ile Ile His 530 535 540 Ala Leu Leu Val Lys Asp Ile Gln Gly Ala Leu His Ser Tyr Lys Glu 545 550 555 560 Ile Ile Ile Glu Ala Thr Lys His Arg Asn Ser Glu Glu Met Trp Arg 565 570 575 Arg Met Asn Leu Met Thr Pro Glu Ala Leu Gly Lys Leu Lys Glu Glu 580 585 590 Met Lys Ser Cys Gly Val Ser Asn Phe Glu Gln Tyr Thr Gly Asp Asp 595 600 605 Cys Trp Val Asn Leu Ser Tyr Thr Val Val Ala Phe Thr Lys Gln Thr 610 615 620 Met Gly Phe Leu Glu Glu Ala Leu Lys Leu Tyr Phe Pro Glu Leu His 625 630 635 640 Met Val Leu Leu Glu Ser Leu Val Glu Ile Ile Leu Val Ala Val Gln 645 650 655 His Val Asp Tyr Ser Leu Arg Cys Glu Gln Asp Pro Glu Lys Lys Ala 660 665 670 Phe Ile Arg Gln Asn Ala Ser Phe Leu Tyr Glu Thr Val Leu Pro Val 675 680 685 Val Glu Lys Arg Phe Glu Glu Gly Val Gly Lys Pro Ala Lys Gln Leu 690 695 700 Gln Asp Leu Arg Asn Ala Ser Arg Leu Ile Arg Val Asn Pro Glu Ser 705 710 715 720 Thr Thr Ser Val Val 725 <210> 90 <211> 523 <212> PRT <213> Homo sapiens <400> 90 Met Gln Arg Ala Ala Ala Leu Val Arg Arg Gly Cys Gly Pro Arg Thr 1 5 10 15 Pro Ser Ser Trp Gly Arg Ser Gln Ser Ser Ala Ala Ala Glu Ala Ser 20 25 30 Ala Val Leu Lys Val Arg Pro Glu Arg Ser Arg Arg Glu Arg Ile Leu 35 40 45 Thr Leu Glu Ser Met Asn Pro Gln Val Lys Ala Val Glu Tyr Ala Val 50 55 60 Arg Gly Pro Ile Val Leu Lys Ala Gly Glu Ile Glu Leu Glu Leu Gln 65 70 75 80 Arg Gly Ile Lys Lys Pro Phe Thr Glu Val Ile Arg Ala Asn Ile Gly 85 90 95 Asp Ala Gln Ala Met Gly Gln Gln Pro Ile Thr Phe Leu Arg Gln Val 100 105 110 Met Ala Leu Cys Thr Tyr Pro Asn Leu Leu Asp Ser Pro Ser Phe Pro 115 120 125 Glu Asp Ala Lys Lys Arg Ala Arg Arg Ile Leu Gln Ala Cys Gly Gly 130 135 140 Asn Ser Leu Gly Ser Tyr Ser Ala Ser Gln Gly Val Asn Cys Ile Arg 145 150 155 160 Glu Asp Val Ala Ala Tyr Ile Thr Arg Arg Asp Gly Gly Val Pro Ala 165 170 175 Asp Pro Asp Asn Ile Tyr Leu Thr Thr Gly Ala Ser Asp Gly Ile Ser 180 185 190 Thr Ile Leu Lys Ile Leu Val Ser Gly Gly Gly Lys Ser Arg Thr Gly 195 200 205 Val Met Ile Pro Ile Pro Gln Tyr Pro Leu Tyr Ser Ala Val Ile Ser 210 215 220 Glu Leu Asp Ala Ile Gln Val Asn Tyr Tyr Leu Asp Glu Glu Asn Cys 225 230 235 240 Trp Ala Leu Asn Val Asn Glu Leu Arg Arg Ala Val Gln Glu Ala Lys 245 250 255 Asp His Cys Asp Pro Lys Val Leu Cys Ile Ile Asn Pro Gly Asn Pro 260 265 270 Thr Gly Gln Val Gln Ser Arg Lys Cys Ile Glu Asp Val Ile His Phe 275 280 285 Ala Trp Glu Glu Lys Leu Phe Leu Leu Ala Asp Glu Val Tyr Gln Asp 290 295 300 Asn Val Tyr Ser Pro Asp Cys Arg Phe His Ser Phe Lys Lys Val Leu 305 310 315 320 Tyr Glu Met Gly Pro Glu Tyr Ser Ser Asn Val Glu Leu Ala Ser Phe 325 330 335 His Ser Thr Ser Lys Gly Tyr Met Gly Glu Cys Gly Tyr Arg Gly Gly 340 345 350 Tyr Met Glu Val Ile Asn Leu His Pro Glu Ile Lys Gly Gln Leu Val 355 360 365 Lys Leu Leu Ser Val Arg Leu Cys Pro Pro Val Ser Gly Gln Ala Ala 370 375 380 Met Asp Ile Val Val Asn Pro Pro Val Ala Gly Glu Glu Ser Phe Glu 385 390 395 400 Gln Phe Ser Arg Glu Lys Glu Ser Val Leu Gly Asn Leu Ala Lys Lys 405 410 415 Ala Lys Leu Thr Glu Asp Leu Phe Asn Gln Val Pro Gly Ile His Cys 420 425 430 Asn Pro Leu Gln Gly Ala Met Tyr Ala Phe Pro Arg Ile Phe Ile Pro 435 440 445 Ala Lys Ala Val Glu Ala Ala Gln Ala His Gln Met Ala Pro Asp Met 450 455 460 Phe Tyr Cys Met Lys Leu Leu Glu Glu Thr Gly Ile Cys Val Val Pro 465 470 475 480 Gly Ser Gly Phe Gly Gln Arg Glu Gly Thr Tyr His Phe Arg Met Thr 485 490 495 Ile Leu Pro Pro Val Glu Lys Leu Lys Thr Val Leu Gln Lys Val Lys 500 505 510 Asp Phe His Ile Asn Phe Leu Glu Lys Tyr Ala 515 520 <210> 91 <211> 1583 <212> PRT <213> Homo sapiens <400> 91 Met Lys Gln Glu Val Glu Asp Ser Val Thr Lys Met Gly Asp Ala His 1 5 10 15 Lys Glu Leu Glu Gln Ser His Ile Asn Tyr Val Lys Glu Ile Glu Asn 20 25 30 Leu Lys Asn Glu Leu Met Ala Val Arg Ser Lys Tyr Ser Glu Asp Lys 35 40 45 Ala Asn Leu Gln Lys Gln Leu Glu Glu Ala Met Asn Thr Gln Leu Glu 50 55 60 Leu Ser Glu Gln Leu Lys Phe Gln Asn Asn Ser Glu Asp Asn Val Lys 65 70 75 80 Lys Leu Gln Glu Glu Ile Glu Lys Ile Arg Pro Gly Phe Glu Glu Gln 85 90 95 Ile Leu Tyr Leu Gln Lys Gln Leu Asp Ala Thr Thr Asp Glu Lys Lys 100 105 110 Glu Thr Val Thr Gln Leu Gln Asn Ile Ile Glu Ala Asn Ser Gln His 115 120 125 Tyr Gln Lys Asn Ile Asn Ser Leu Gln Glu Glu Leu Leu Gln Leu Lys 130 135 140 Ala Ile His Gln Glu Glu Val Lys Glu Leu Met Cys Gln Ile Glu Ala 145 150 155 160 Ser Ala Lys Glu His Glu Ala Glu Ile Asn Lys Leu Asn Glu Leu Lys 165 170 175 Glu Asn Leu Val Lys Gln Cys Glu Ala Ser Glu Lys Asn Ile Gln Lys 180 185 190 Lys Tyr Glu Cys Glu Leu Glu Asn Leu Arg Lys Ala Thr Ser Asn Ala 195 200 205 Asn Gln Asp Asn Gln Ile Cys Ser Ile Leu Leu Gln Glu Asn Thr Phe 210 215 220 Val Glu Gln Val Val Asn Glu Lys Val Lys His Leu Glu Asp Thr Leu 225 230 235 240 Lys Glu Leu Glu Ser Gln His Ser Ile Leu Lys Asp Glu Val Thr Tyr 245 250 255 Met Asn Asn Leu Lys Leu Lys Leu Glu Met Asp Ala Gln His Ile Lys 260 265 270 Asp Glu Phe Phe His Glu Arg Glu Asp Leu Glu Phe Lys Ile Asn Glu 275 280 285 Leu Leu Leu Ala Lys Glu Glu Gln Gly Cys Val Ile Glu Lys Leu Lys 290 295 300 Ser Glu Leu Ala Gly Leu Asn Lys Gln Phe Cys Tyr Thr Val Glu Gln 305 310 315 320 His Asn Arg Glu Val Gln Ser Leu Lys Glu Gln His Gln Lys Glu Ile 325 330 335 Ser Glu Leu Asn Glu Thr Phe Leu Ser Asp Ser Glu Lys Glu Lys Leu 340 345 350 Thr Leu Met Phe Glu Ile Gln Gly Leu Lys Glu Gln Cys Glu Asn Leu 355 360 365 Gln Gln Glu Lys Gln Glu Ala Ile Leu Asn Tyr Glu Ser Leu Arg Glu 370 375 380 Ile Met Glu Ile Leu Gln Thr Glu Leu Gly Glu Ser Ala Gly Lys Ile 385 390 395 400 Ser Gln Glu Phe Glu Ser Met Lys Gln Gln Gln Ala Ser Asp Val His 405 410 415 Glu Leu Gln Gln Lys Leu Arg Thr Ala Phe Thr Glu Lys Asp Ala Leu 420 425 430 Leu Glu Thr Val Asn Arg Leu Gln Gly Glu Asn Glu Lys Leu Leu Ser 435 440 445 Gln Gln Glu Leu Val Pro Glu Leu Glu Asn Thr Ile Lys Asn Leu Gln 450 455 460 Glu Lys Asn Gly Val Tyr Leu Leu Ser Leu Ser Gln Arg Asp Thr Met 465 470 475 480 Leu Lys Glu Leu Glu Gly Lys Ile Asn Ser Leu Thr Glu Glu Lys Asp 485 490 495 Asp Phe Ile Asn Lys Leu Lys Asn Ser His Glu Glu Met Asp Asn Phe 500 505 510 His Lys Lys Cys Glu Arg Glu Glu Arg Leu Ile Leu Glu Leu Gly Lys 515 520 525 Lys Val Glu Gln Thr Ile Gln Tyr Asn Ser Glu Leu Glu Gln Lys Val 530 535 540 Asn Glu Leu Thr Gly Gly Leu Glu Glu Thr Leu Lys Glu Lys Asp Gln 545 550 555 560 Asn Asp Gln Lys Leu Glu Lys Leu Met Val Gln Met Lys Val Leu Ser 565 570 575 Glu Asp Lys Glu Val Leu Ser Ala Glu Val Lys Ser Leu Tyr Glu Glu 580 585 590 Asn Asn Lys Leu Ser Ser Glu Lys Lys Gln Leu Ser Arg Asp Leu Glu 595 600 605 Val Phe Leu Ser Gln Lys Glu Asp Val Ile Leu Lys Glu His Ile Thr 610 615 620 Gln Leu Glu Lys Lys Leu Gln Leu Met Val Glu Glu Gln Asp Asn Leu 625 630 635 640 Asn Lys Leu Leu Glu Asn Glu Gln Val Gln Lys Leu Phe Val Lys Thr 645 650 655 Gln Leu Tyr Gly Phe Leu Lys Glu Met Gly Ser Glu Val Ser Glu Asp 660 665 670 Ser Glu Glu Lys Asp Val Val Asn Val Leu Gln Ala Val Gly Glu Ser 675 680 685 Leu Ala Lys Ile Asn Glu Glu Lys Cys Asn Leu Ala Phe Gln Arg Asp 690 695 700 Glu Lys Val Leu Glu Leu Glu Lys Glu Ile Lys Cys Leu Gln Glu Glu 705 710 715 720 Ser Val Val Gln Cys Glu Glu Leu Lys Ser Leu Leu Arg Asp Tyr Glu 725 730 735 Gln Glu Lys Val Leu Leu Arg Lys Glu Leu Glu Glu Ile Gln Ser Glu 740 745 750 Lys Glu Ala Leu Gln Ser Asp Leu Leu Glu Met Lys Asn Ala Asn Glu 755 760 765 Lys Thr Arg Leu Glu Asn Gln Asn Leu Leu Ile Gln Val Glu Glu Val 770 775 780 Ser Gln Thr Cys Ser Lys Ser Glu Ile His Asn Glu Lys Glu Lys Cys 785 790 795 800 Phe Ile Lys Glu His Glu Asn Leu Lys Pro Leu Leu Glu Gln Lys Glu 805 810 815 Leu Arg Asp Arg Arg Ala Glu Leu Ile Leu Leu Lys Asp Ser Leu Ala 820 825 830 Lys Ser Pro Ser Val Lys Asn Asp Pro Leu Ser Ser Val Lys Glu Leu 835 840 845 Glu Glu Lys Ile Glu Asn Leu Glu Lys Glu Cys Lys Glu Lys Glu Glu 850 855 860 Lys Ile Asn Lys Ile Lys Leu Val Ala Val Lys Ala Lys Lys Glu Leu 865 870 875 880 Asp Ser Ser Arg Lys Glu Thr Gln Thr Val Lys Glu Glu Leu Glu Ser 885 890 895 Leu Arg Ser Glu Lys Asp Gln Leu Ser Ala Ser Met Arg Asp Leu Ile 900 905 910 Gln Gly Ala Glu Ser Tyr Lys Asn Leu Leu Leu Glu Tyr Glu Lys Gln 915 920 925 Ser Glu Gln Leu Asp Val Glu Lys Glu Arg Ala Asn Asn Phe Glu His 930 935 940 Arg Ile Glu Asp Leu Thr Arg Gln Leu Arg Asn Ser Thr Leu Gln Cys 945 950 955 960 Glu Thr Ile Asn Ser Asp Asn Glu Asp Leu Leu Ala Arg Ile Glu Thr 965 970 975 Leu Gln Ser Asn Ala Lys Leu Leu Glu Val Gln Ile Leu Glu Val Gln 980 985 990 Arg Ala Lys Ala Met Val Asp Lys Glu Leu Glu Ala Glu Lys Leu Gln 995 1000 1005 Lys Glu Gln Lys Ile Lys Glu His Ala Thr Thr Val Asn Glu Leu Glu 1010 1015 1020 Glu Leu Gln Val Gln Leu Gln Lys Glu Lys Lys Gln Leu Gln Lys Thr 1025 1030 1035 1040 Met Gln Glu Leu Glu Leu Val Lys Lys Asp Ala Gln Gln Thr Thr Leu 1045 1050 1055 Met Asn Met Glu Ile Ala Asp Tyr Glu Arg Leu Met Lys Glu Leu Asn 1060 1065 1070 Gln Lys Leu Thr Asn Lys Asn Asn Lys Ile Glu Asp Leu Glu Gln Glu 1075 1080 1085 Ile Lys Ile Gln Lys Gln Lys Gln Glu Thr Leu Gln Glu Glu Ile Thr 1090 1095 1100 Ser Leu Gln Ser Ser Val Gln Gln Tyr Glu Glu Lys Asn Thr Lys Ile 1105 1110 1115 1120 Lys Gln Leu Leu Val Lys Thr Lys Lys Glu Leu Ala Asp Ser Lys Gln 1125 1130 1135 Ala Glu Thr Asp His Leu Ile Leu Gln Ala Ser Leu Lys Gly Glu Leu 1140 1145 1150 Glu Ala Ser Gln Gln Gln Val Glu Val Tyr Lys Ile Gln Leu Ala Glu 1155 1160 1165 Ile Thr Ser Glu Lys His Lys Ile His Glu His Leu Lys Thr Ser Ala 1170 1175 1180 Glu Gln His Gln Arg Thr Leu Ser Ala Tyr Gln Gln Arg Val Thr Ala 1185 1190 1195 1200 Leu Gln Glu Glu Cys Arg Ala Ala Lys Ala Glu Gln Ala Thr Val Thr 1205 1210 1215 Ser Glu Phe Glu Ser Tyr Lys Val Arg Val His Asn Val Leu Lys Gln 1220 1225 1230 Gln Lys Asn Lys Ser Met Ser Gln Ala Glu Thr Glu Gly Ala Lys Gln 1235 1240 1245 Glu Arg Glu His Leu Glu Met Leu Ile Asp Gln Leu Lys Ile Lys Leu 1250 1255 1260 Gln Asp Ser Gln Asn Asn Leu Gln Ile Asn Val Ser Glu Leu Gln Thr 1265 1270 1275 1280 Leu Gln Ser Glu His Asp Thr Leu Leu Glu Arg His Asn Lys Met Leu 1285 1290 1295 Gln Glu Thr Val Ser Lys Glu Ala Glu Leu Arg Glu Lys Leu Cys Ser 1300 1305 1310 Ile Gln Ser Glu Asn Met Met Met Lys Ser Glu His Thr Gln Thr Val 1315 1320 1325 Ser Gln Leu Thr Ser Gln Asn Glu Val Leu Arg Asn Ser Phe Arg Asp 1330 1335 1340 Gln Val Arg His Leu Gln Glu Glu His Arg Lys Thr Val Glu Thr Leu 1345 1350 1355 1360 Gln Gln Gln Leu Ser Lys Met Glu Ala Gln Leu Phe Gln Leu Lys Asn 1365 1370 1375 Glu Pro Thr Thr Arg Ser Pro Val Ser Ser Gln Gln Ser Leu Lys Asn 1380 1385 1390 Leu Arg Glu Arg Arg Asn Thr Asp Leu Pro Leu Leu Asp Met His Thr 1395 1400 1405 Val Thr Arg Glu Glu Gly Glu Gly Met Glu Thr Thr Asp Thr Glu Ser 1410 1415 1420 Val Ser Ser Ala Ser Thr Tyr Thr Gln Ser Leu Glu Gln Leu Leu Asn 1425 1430 1435 1440 Ser Pro Glu Thr Lys Leu Glu Pro Pro Leu Trp His Ala Glu Phe Thr 1445 1450 1455 Lys Glu Glu Leu Val Gln Lys Leu Ser Ser Thr Thr Lys Ser Ala Asp 1460 1465 1470 His Leu Asn Gly Leu Leu Arg Glu Thr Glu Ala Thr Asn Ala Ile Leu 1475 1480 1485 Met Glu Gln Ile Lys Leu Leu Lys Ser Glu Ile Arg Arg Leu Glu Arg 1490 1495 1500 Asn Gln Glu Arg Glu Lys Ser Ala Ala Asn Leu Glu Tyr Leu Lys Asn 1505 1510 1515 1520 Val Leu Leu Gln Phe Ile Phe Leu Lys Pro Gly Ser Glu Arg Glu Arg 1525 1530 1535 Leu Leu Pro Val Ile Asn Thr Met Leu Gln Leu Ser Pro Glu Glu Lys 1540 1545 1550 Gly Lys Leu Ala Ala Val Ala Gln Gly Glu Glu Glu Asn Ala Ser Arg 1555 1560 1565 Ser Ser Gly Trp Ala Ser Tyr Leu His Ser Trp Ser Gly Leu Arg 1570 1575 1580 <210> 92 <211> 1057 <212> PRT <213> Homo sapiens <400> 92 Met Leu Cys Trp Gly Asn Ala Ser Phe Gly Gln Leu Gly Leu Gly Gly 1 5 10 15 Ile Asp Glu Glu Ile Val Leu Glu Pro Arg Lys Ser Asp Phe Phe Ile 20 25 30 Asn Lys Arg Val Arg Asp Val Gly Cys Gly Leu Arg His Thr Val Phe 35 40 45 Val Leu Asp Asp Gly Thr Val Tyr Thr Cys Gly Cys Asn Asp Leu Gly 50 55 60 Gln Leu Gly His Glu Lys Ser Arg Lys Lys Pro Glu Gln Val Val Ala 65 70 75 80 Leu Asp Ala Gln Asn Ile Val Ala Val Ser Cys Gly Glu Ala His Thr 85 90 95 Leu Ala Leu Asn Asp Lys Gly Gln Val Tyr Ala Trp Gly Leu Asp Ser 100 105 110 Asp Gly Gln Leu Gly Leu Val Gly Ser Glu Glu Cys Ile Arg Val Pro 115 120 125 Arg Asn Ile Lys Ser Leu Ser Asp Ile Gln Ile Val Gln Val Ala Cys 130 135 140 Gly Tyr Tyr His Ser Leu Ala Leu Ser Lys Ala Ser Glu Val Phe Cys 145 150 155 160 Trp Gly Gln Asn Lys Tyr Gly Gln Leu Gly Leu Gly Thr Asp Cys Lys 165 170 175 Lys Gln Thr Ser Pro Gln Leu Leu Lys Ser Leu Leu Gly Ile Pro Phe 180 185 190 Met Gln Val Ala Ala Gly Gly Ala His Ser Phe Val Leu Thr Leu Ser 195 200 205 Gly Ala Ile Phe Gly Trp Gly Arg Asn Lys Phe Gly Gln Leu Gly Leu 210 215 220 Asn Asp Glu Asn Asp Arg Tyr Val Pro Asn Leu Leu Lys Ser Leu Arg 225 230 235 240 Ser Gln Lys Ile Val Tyr Ile Cys Cys Gly Glu Asp His Thr Ala Ala 245 250 255 Leu Thr Lys Glu Gly Gly Val Phe Thr Phe Gly Ala Gly Gly Tyr Gly 260 265 270 Gln Leu Gly His Asn Ser Thr Ser His Glu Ile Asn Pro Arg Lys Val 275 280 285 Phe Glu Leu Met Gly Ser Ile Val Thr Glu Ile Ala Cys Gly Arg Gln 290 295 300 His Thr Ser Ala Phe Val Pro Ser Ser Gly Arg Ile Tyr Ser Phe Gly 305 310 315 320 Leu Gly Gly Asn Gly Gln Leu Gly Thr Gly Ser Thr Ser Asn Arg Lys 325 330 335 Ser Pro Phe Thr Val Lys Gly Asn Trp Tyr Pro Tyr Asn Gly Gln Cys 340 345 350 Leu Pro Asp Ile Asp Ser Glu Glu Tyr Phe Cys Val Lys Arg Ile Phe 355 360 365 Ser Gly Gly Asp Gln Ser Phe Ser His Tyr Ser Ser Pro Gln Asn Cys 370 375 380 Gly Pro Pro Asp Asp Phe Arg Cys Pro Asn Pro Thr Lys Gln Ile Trp 385 390 395 400 Thr Val Asn Glu Ala Leu Ile Gln Lys Trp Leu Ser Tyr Pro Ser Gly 405 410 415 Arg Phe Pro Val Glu Ile Ala Asn Glu Ile Asp Gly Thr Phe Ser Ser 420 425 430 Ser Gly Cys Leu Asn Gly Ser Phe Leu Ala Val Ser Asn Asp Asp His 435 440 445 Tyr Arg Thr Gly Thr Arg Phe Ser Gly Val Asp Met Asn Ala Ala Arg 450 455 460 Leu Leu Phe His Lys Leu Ile Gln Pro Asp His Pro Gln Ile Ser Gln 465 470 475 480 Gln Val Ala Ala Ser Leu Glu Lys Asn Leu Ile Pro Lys Leu Thr Ser 485 490 495 Ser Leu Pro Asp Val Glu Ala Leu Arg Phe Tyr Leu Thr Leu Pro Glu 500 505 510 Cys Pro Leu Met Ser Asp Ser Asn Asn Phe Thr Thr Ile Ala Ile Pro 515 520 525 Phe Gly Thr Ala Leu Val Asn Leu Glu Lys Ala Pro Leu Lys Val Leu 530 535 540 Glu Asn Trp Trp Ser Val Leu Glu Pro Pro Leu Phe Leu Lys Ile Val 545 550 555 560 Glu Leu Phe Lys Glu Val Val Val His Leu Leu Lys Leu Tyr Lys Ile 565 570 575 Gly Ile Pro Pro Ser Glu Arg Arg Ile Phe Asn Ser Phe Leu His Thr 580 585 590 Ala Leu Lys Val Leu Glu Ile Leu His Arg Val Asn Glu Lys Met Gly 595 600 605 Gln Ile Ile Gln Tyr Asp Lys Phe Tyr Ile His Glu Val Gln Glu Leu 610 615 620 Ile Asp Ile Arg Asn Asp Tyr Ile Asn Trp Val Gln Gln Gln Ala Tyr 625 630 635 640 Gly Met Asp Val Asn His Gly Leu Thr Glu Leu Ala Asp Ile Pro Val 645 650 655 Thr Ile Cys Thr Tyr Pro Phe Val Phe Asp Ala Gln Ala Lys Thr Thr 660 665 670 Leu Leu Gln Thr Asp Ala Val Leu Gln Met Gln Met Ala Ile Asp Gln 675 680 685 Ala His Arg Gln Asn Val Ser Ser Leu Phe Leu Pro Val Ile Glu Ser 690 695 700 Val Asn Pro Cys Leu Ile Leu Val Val Arg Arg Glu Asn Ile Val Gly 705 710 715 720 Asp Ala Met Glu Val Leu Arg Lys Thr Lys Asn Ile Asp Tyr Lys Lys 725 730 735 Pro Leu Lys Val Ile Phe Val Gly Glu Asp Ala Val Asp Ala Gly Gly 740 745 750 Val Arg Lys Glu Phe Phe Leu Leu Ile Met Arg Glu Leu Leu Asp Pro 755 760 765 Lys Tyr Gly Met Phe Arg Tyr Tyr Glu Asp Ser Arg Leu Ile Trp Phe 770 775 780 Ser Asp Lys Thr Phe Glu Asp Ser Asp Leu Phe His Leu Ile Gly Val 785 790 795 800 Ile Cys Gly Leu Ala Ile Tyr Asn Cys Thr Ile Val Asp Leu His Phe 805 810 815 Pro Leu Ala Leu Tyr Lys Lys Leu Leu Lys Lys Lys Pro Ser Leu Asp 820 825 830 Asp Leu Lys Glu Leu Met Pro Asp Val Gly Arg Ser Met Gln Gln Leu 835 840 845 Leu Asp Tyr Pro Glu Asp Asp Ile Glu Glu Thr Phe Cys Leu Asn Phe 850 855 860 Thr Ile Thr Val Glu Asn Phe Gly Ala Thr Glu Val Lys Glu Leu Val 865 870 875 880 Leu Asn Gly Ala Asp Thr Ala Val Asn Lys Gln Asn Arg Gln Glu Phe 885 890 895 Val Asp Ala Tyr Val Asp Tyr Ile Phe Asn Lys Ser Val Ala Ser Leu 900 905 910 Phe Asp Ala Phe His Ala Gly Phe His Lys Val Cys Gly Gly Lys Val 915 920 925 Leu Leu Leu Phe Gln Pro Asn Glu Leu Gln Ala Met Val Ile Gly Asn 930 935 940 Thr Asn Tyr Asp Trp Lys Glu Leu Glu Lys Asn Thr Glu Tyr Lys Gly 945 950 955 960 Glu Tyr Trp Ala Glu His Pro Thr Ile Lys Ile Phe Trp Glu Val Phe 965 970 975 His Glu Leu Pro Leu Glu Lys Lys Lys Gln Phe Leu Leu Phe Leu Thr 980 985 990 Gly Ser Asp Arg Ile Pro Ile Leu Gly Met Lys Ser Leu Lys Leu Val 995 1000 1005 Ile Gln Ser Thr Gly Gly Gly Glu Glu Tyr Leu Pro Val Ser His Thr 1010 1015 1020 Cys Phe Asn Leu Leu Asp Leu Pro Lys Tyr Thr Glu Lys Glu Thr Leu 1025 1030 1035 1040 Arg Ser Lys Leu Ile Gln Ala Ile Asp His Asn Glu Gly Phe Ser Leu 1045 1050 1055 Ile <210> 93 <211> 3859 <212> PRT <213> Homo sapiens <400> 93 Met Ala Phe Val Ala Thr Gln Gly Ala Thr Val Val Asp Gln Thr Thr 1 5 10 15 Leu Met Lys Lys Tyr Leu Gln Phe Val Ala Ala Leu Thr Asp Val Asn 20 25 30 Thr Pro Asp Glu Thr Lys Leu Lys Met Met Gln Glu Val Ser Glu Asn 35 40 45 Phe Glu Asn Val Thr Ser Ser Pro Gln Tyr Ser Thr Phe Leu Glu His 50 55 60 Ile Ile Pro Arg Phe Leu Thr Phe Leu Gln Asp Gly Glu Val Gln Phe 65 70 75 80 Leu Gln Glu Lys Pro Ala Gln Gln Leu Arg Lys Leu Val Leu Glu Ile 85 90 95 Ile His Arg Ile Pro Thr Asn Glu His Leu Arg Pro His Thr Lys Asn 100 105 110 Val Leu Ser Val Met Phe Arg Phe Leu Glu Thr Glu Asn Glu Glu Asn 115 120 125 Val Leu Ile Cys Leu Arg Ile Ile Ile Glu Leu His Lys Gln Phe Arg 130 135 140 Pro Pro Ile Thr Gln Glu Ile His His Phe Leu Asp Phe Val Lys Gln 145 150 155 160 Ile Tyr Lys Glu Leu Pro Lys Val Val Asn Arg Tyr Phe Glu Asn Pro 165 170 175 Gln Val Ile Pro Glu Asn Thr Val Pro Pro Pro Glu Met Val Gly Met 180 185 190 Ile Thr Thr Ile Ala Val Lys Val Asn Pro Glu Arg Glu Asp Ser Glu 195 200 205 Thr Arg Thr His Ser Ile Ile Pro Arg Gly Ser Leu Ser Leu Lys Val 210 215 220 Leu Ala Glu Leu Pro Ile Ile Val Val Leu Met Tyr Gln Leu Tyr Lys 225 230 235 240 Leu Asn Ile His Asn Val Val Ala Glu Phe Val Pro Leu Ile Met Asn 245 250 255 Thr Ile Ala Ile Gln Val Ser Ala Gln Ala Arg Gln His Lys Leu Tyr 260 265 270 Asn Lys Glu Leu Tyr Ala Asp Phe Ile Ala Ala Gln Ile Lys Thr Leu 275 280 285 Ser Phe Leu Ala Tyr Ile Ile Arg Ile Tyr Gln Glu Leu Val Thr Lys 290 295 300 Tyr Ser Gln Gln Met Val Lys Gly Met Leu Gln Leu Leu Ser Asn Cys 305 310 315 320 Pro Ala Glu Thr Ala His Leu Arg Lys Glu Leu Leu Ile Ala Ala Lys 325 330 335 His Ile Leu Thr Thr Glu Leu Arg Asn Gln Phe Ile Pro Cys Met Asp 340 345 350 Lys Leu Phe Asp Glu Ser Ile Leu Ile Gly Ser Gly Tyr Thr Ala Arg 355 360 365 Glu Thr Leu Arg Pro Leu Ala Tyr Ser Thr Leu Ala Asp Leu Val His 370 375 380 His Val Arg Gln His Leu Pro Leu Ser Asp Leu Ser Leu Ala Val Gln 385 390 395 400 Leu Phe Ala Lys Asn Ile Asp Asp Glu Ser Leu Pro Ser Ser Ile Gln 405 410 415 Thr Met Ser Cys Lys Leu Leu Leu Asn Leu Val Asp Cys Ile Arg Ser 420 425 430 Lys Ser Glu Gln Glu Ser Gly Asn Gly Arg Asp Val Leu Met Arg Met 435 440 445 Leu Glu Val Phe Val Leu Lys Phe His Thr Ile Ala Arg Tyr Gln Leu 450 455 460 Ser Ala Ile Phe Lys Lys Cys Lys Pro Gln Ser Glu Leu Gly Ala Val 465 470 475 480 Glu Ala Ala Leu Pro Gly Val Pro Thr Ala Pro Ala Ala Pro Gly Pro 485 490 495 Ala Pro Ser Pro Ala Pro Val Pro Ala Pro Pro Pro Pro Pro Pro Pro 500 505 510 Pro Pro Pro Ala Thr Pro Val Thr Pro Ala Pro Val Pro Pro Phe Glu 515 520 525 Lys Gln Gly Glu Lys Asp Lys Glu Asp Lys Gln Thr Phe Gln Val Thr 530 535 540 Asp Cys Arg Ser Leu Val Lys Thr Leu Val Cys Gly Val Lys Thr Ile 545 550 555 560 Thr Trp Gly Ile Thr Ser Cys Lys Ala Pro Gly Glu Ala Gln Phe Ile 565 570 575 Pro Asn Lys Gln Leu Gln Pro Lys Glu Thr Gln Ile Tyr Ile Lys Leu 580 585 590 Val Lys Tyr Ala Met Gln Ala Leu Asp Ile Tyr Gln Val Gln Ile Ala 595 600 605 Gly Asn Gly Gln Thr Tyr Ile Arg Val Ala Asn Cys Gln Thr Val Arg 610 615 620 Met Lys Glu Glu Lys Glu Val Leu Glu His Phe Ala Gly Val Phe Thr 625 630 635 640 Met Met Asn Pro Leu Thr Phe Lys Glu Ile Phe Gln Thr Thr Val Pro 645 650 655 Tyr Met Val Glu Arg Ile Ser Lys Asn Tyr Ala Leu Gln Ile Val Ala 660 665 670 Asn Ser Phe Leu Ala Asn Pro Thr Thr Ser Ala Leu Phe Ala Thr Ile 675 680 685 Leu Val Glu Tyr Leu Leu Asp Arg Leu Pro Glu Met Gly Ser Asn Val 690 695 700 Glu Leu Ser Asn Leu Tyr Leu Lys Leu Phe Lys Leu Val Phe Gly Ser 705 710 715 720 Val Ser Leu Phe Ala Ala Glu Asn Glu Gln Met Leu Lys Pro His Leu 725 730 735 His Lys Ile Val Asn Ser Ser Met Glu Leu Ala Gln Thr Ala Lys Glu 740 745 750 Pro Tyr Asn Tyr Phe Leu Leu Leu Arg Ala Leu Phe Arg Ser Ile Gly 755 760 765 Gly Gly Ser His Asp Leu Leu Tyr Gln Glu Phe Leu Pro Leu Leu Pro 770 775 780 Asn Leu Leu Gln Gly Leu Asn Met Leu Gln Ser Gly Leu His Lys Gln 785 790 795 800 His Met Lys Asp Leu Phe Val Glu Leu Cys Leu Thr Val Pro Val Arg 805 810 815 Leu Ser Ser Leu Leu Pro Tyr Leu Pro Met Leu Met Asp Pro Leu Val 820 825 830 Ser Ala Leu Asn Gly Ser Gln Thr Leu Val Ser Gln Gly Leu Arg Thr 835 840 845 Leu Glu Leu Cys Val Asp Asn Leu Gln Pro Asp Phe Leu Tyr Asp His 850 855 860 Ile Gln Pro Val Arg Ala Glu Leu Met Gln Ala Leu Trp Arg Thr Leu 865 870 875 880 Arg Asn Pro Ala Asp Ser Ile Ser His Val Ala Tyr Arg Val Leu Gly 885 890 895 Lys Phe Gly Gly Ser Asn Arg Lys Met Leu Lys Glu Ser Gln Lys Leu 900 905 910 His Tyr Val Val Thr Glu Val Gln Gly Pro Ser Ile Thr Val Glu Phe 915 920 925 Ser Asp Cys Lys Ala Ser Leu Gln Leu Pro Met Glu Lys Ala Ile Glu 930 935 940 Thr Ala Leu Asp Cys Leu Lys Ser Ala Asn Thr Glu Pro Tyr Tyr Arg 945 950 955 960 Arg Gln Ala Trp Glu Val Ile Lys Cys Phe Leu Val Ala Met Met Ser 965 970 975 Leu Glu Asp Asn Lys His Ala Leu Tyr Gln Leu Leu Ala His Pro Asn 980 985 990 Phe Thr Glu Lys Thr Ile Pro Asn Val Ile Ile Ser His Arg Tyr Lys 995 1000 1005 Ala Gln Asp Thr Pro Ala Arg Lys Thr Phe Glu Gln Ala Leu Thr Gly 1010 1015 1020 Ala Phe Met Ser Ala Val Ile Lys Asp Leu Arg Pro Ser Ala Leu Pro 1025 1030 1035 1040 Phe Val Ala Ser Leu Ile Arg His Tyr Thr Met Val Ala Val Ala Gln 1045 1050 1055 Gln Cys Gly Pro Phe Leu Leu Pro Cys Tyr Gln Val Gly Ser Gln Pro 1060 1065 1070 Ser Thr Ala Met Phe His Ser Glu Glu Asn Gly Ser Lys Gly Met Asp 1075 1080 1085 Pro Leu Val Leu Ile Asp Ala Ile Ala Ile Cys Met Ala Tyr Glu Glu 1090 1095 1100 Lys Glu Leu Cys Lys Ile Gly Glu Val Ala Leu Ala Val Ile Phe Asp 1105 1110 1115 1120 Val Ala Ser Ile Ile Leu Gly Ser Lys Glu Arg Ala Cys Gln Leu Pro 1125 1130 1135 Leu Phe Ser Tyr Ile Val Glu Arg Leu Cys Ala Cys Cys Tyr Glu Gln 1140 1145 1150 Ala Trp Tyr Ala Lys Leu Gly Gly Val Val Ser Ile Lys Phe Leu Met 1155 1160 1165 Glu Arg Leu Pro Leu Thr Trp Val Leu Gln Asn Gln Gln Thr Phe Leu 1170 1175 1180 Lys Ala Leu Leu Phe Val Met Met Asp Leu Thr Gly Glu Val Ser Asn 1185 1190 1195 1200 Gly Ala Val Ala Met Ala Lys Thr Thr Leu Glu Gln Leu Leu Met Arg 1205 1210 1215 Cys Ala Thr Pro Leu Lys Asp Glu Glu Arg Ala Glu Glu Ile Val Ala 1220 1225 1230 Ala Gln Glu Lys Ser Phe His His Val Thr His Asp Leu Val Arg Glu 1235 1240 1245 Val Thr Ser Pro Asn Ser Thr Val Arg Lys Gln Ala Met His Ser Leu 1250 1255 1260 Gln Val Leu Ala Gln Val Thr Gly Lys Ser Val Thr Val Ile Met Glu 1265 1270 1275 1280 Pro His Lys Glu Val Leu Gln Asp Met Val Pro Pro Lys Lys His Leu 1285 1290 1295 Leu Arg His Gln Pro Ala Asn Ala Gln Ile Gly Leu Met Glu Gly Asn 1300 1305 1310 Thr Phe Cys Thr Thr Leu Gln Pro Arg Leu Phe Thr Met Asp Leu Asn 1315 1320 1325 Val Val Glu His Lys Val Phe Tyr Thr Glu Leu Leu Asn Leu Cys Glu 1330 1335 1340 Ala Glu Asp Ser Ala Leu Thr Lys Leu Pro Cys Tyr Lys Ser Leu Pro 1345 1350 1355 1360 Ser Leu Val Pro Leu Arg Ile Ala Ala Leu Asn Ala Leu Ala Ala Cys 1365 1370 1375 Asn Tyr Leu Pro Gln Ser Arg Glu Lys Ile Ile Ala Ala Leu Phe Lys 1380 1385 1390 Ala Leu Asn Ser Thr Asn Ser Glu Leu Gln Glu Ala Gly Glu Ala Cys 1395 1400 1405 Met Arg Lys Phe Leu Glu Gly Ala Thr Ile Glu Val Asp Gln Ile His 1410 1415 1420 Thr His Met Arg Pro Leu Leu Met Met Leu Gly Asp Tyr Arg Ser Leu 1425 1430 1435 1440 Thr Leu Asn Val Val Asn Arg Leu Thr Ser Val Thr Arg Leu Phe Pro 1445 1450 1455 Asn Ser Phe Asn Asp Lys Phe Cys Asp Gln Met Met Gln His Leu Arg 1460 1465 1470 Lys Trp Met Glu Val Val Val Ile Thr His Lys Gly Gly Gln Arg Ser 1475 1480 1485 Asp Gly Asn Glu Ser Ile Ser Glu Cys Gly Arg Cys Pro Leu Ser Pro 1490 1495 1500 Phe Cys Gln Phe Glu Glu Met Lys Ile Cys Ser Ala Ile Ile Asn Leu 1505 1510 1515 1520 Phe His Leu Ile Pro Ala Ala Pro Gln Thr Leu Val Lys Pro Leu Leu 1525 1530 1535 Glu Val Val Met Lys Thr Glu Arg Ala Met Leu Ile Glu Ala Gly Ser 1540 1545 1550 Pro Phe Arg Glu Pro Leu Ile Lys Phe Leu Thr Arg His Pro Ser Gln 1555 1560 1565 Thr Val Glu Leu Phe Met Met Glu Ala Thr Leu Asn Asp Pro Gln Trp 1570 1575 1580 Ser Arg Met Phe Met Ser Phe Leu Lys His Lys Asp Ala Arg Pro Leu 1585 1590 1595 1600 Arg Asp Val Leu Ala Ala Asn Pro Asn Arg Phe Ile Thr Leu Leu Leu 1605 1610 1615 Pro Gly Gly Ala Gln Thr Ala Val Arg Pro Gly Ser Pro Ser Thr Ser 1620 1625 1630 Thr Met Arg Leu Asp Leu Gln Phe Gln Ala Ile Lys Ile Ile Ser Ile 1635 1640 1645 Ile Val Lys Asn Asp Asp Ser Trp Leu Ala Ser Gln His Ser Leu Val 1650 1655 1660 Ser Gln Leu Arg Arg Val Trp Val Ser Glu Asn Phe Gln Glu Arg His 1665 1670 1675 1680 Arg Lys Glu Asn Met Ala Ala Thr Asn Trp Lys Glu Pro Lys Leu Leu 1685 1690 1695 Ala Tyr Cys Leu Leu Asn Tyr Cys Lys Arg Asn Tyr Gly Asp Ile Glu 1700 1705 1710 Leu Leu Phe Gln Leu Leu Arg Ala Phe Thr Gly Arg Phe Leu Cys Asn 1715 1720 1725 Met Thr Phe Leu Lys Glu Tyr Met Glu Glu Glu Ile Pro Lys Asn Tyr 1730 1735 1740 Ser Ile Ala Gln Lys Arg Ala Leu Phe Phe Arg Phe Val Asp Phe Asn 1745 1750 1755 1760 Asp Pro Asn Phe Gly Asp Glu Leu Lys Ala Lys Val Leu Gln His Ile 1765 1770 1775 Leu Asn Pro Ala Phe Leu Tyr Ser Phe Glu Lys Gly Glu Gly Glu Gln 1780 1785 1790 Leu Leu Gly Pro Pro Asn Pro Glu Gly Asp Asn Pro Glu Ser Ile Thr 1795 1800 1805 Ser Val Phe Ile Thr Lys Val Leu Asp Pro Glu Lys Gln Ala Asp Met 1810 1815 1820 Leu Asp Ser Leu Arg Ile Tyr Leu Leu Gln Tyr Ala Thr Leu Leu Val 1825 1830 1835 1840 Glu His Ala Pro His His Ile His Asp Asn Asn Lys Asn Arg Asn Ser 1845 1850 1855 Lys Leu Arg Arg Leu Met Thr Phe Ala Trp Pro Cys Leu Leu Ser Lys 1860 1865 1870 Ala Cys Val Asp Pro Ala Cys Lys Tyr Ser Gly His Leu Leu Leu Ala 1875 1880 1885 His Ile Ile Ala Lys Phe Ala Ile His Lys Lys Ile Val Leu Gln Val 1890 1895 1900 Phe His Ser Leu Leu Lys Ala His Ala Met Glu Ala Arg Ala Ile Val 1905 1910 1915 1920 Arg Gln Ala Met Ala Ile Leu Thr Pro Ala Val Pro Ala Arg Met Glu 1925 1930 1935 Asp Gly His Gln Met Leu Thr His Trp Thr Arg Lys Ile Ile Val Glu 1940 1945 1950 Glu Gly His Thr Val Pro Gln Leu Val His Ile Leu His Leu Ile Val 1955 1960 1965 Gln His Phe Lys Val Tyr Tyr Pro Val Arg His His Leu Val Gln His 1970 1975 1980 Met Val Ser Ala Met Gln Arg Leu Gly Phe Thr Pro Ser Val Thr Ile 1985 1990 1995 2000 Glu Gln Arg Arg Leu Ala Val Asp Leu Ser Glu Val Val Ile Lys Trp 2005 2010 2015 Glu Leu Gln Arg Ile Lys Asp Gln Gln Pro Asp Ser Asp Met Asp Pro 2020 2025 2030 Asn Ser Ser Gly Glu Gly Val Asn Ser Val Ser Ser Ser Ile Lys Arg 2035 2040 2045 Gly Leu Ser Val Asp Ser Ala Gln Glu Val Lys Arg Phe Arg Thr Ala 2050 2055 2060 Thr Gly Ala Ile Ser Ala Val Phe Gly Arg Ser Gln Ser Leu Pro Gly 2065 2070 2075 2080 Ala Asp Ser Leu Leu Ala Lys Pro Ile Asp Lys Gln His Thr Asp Thr 2085 2090 2095 Val Val Asn Phe Leu Ile Arg Val Ala Cys Gln Val Asn Asp Asn Thr 2100 2105 2110 Asn Thr Ala Gly Ser Pro Gly Glu Val Leu Ser Arg Arg Cys Val Asn 2115 2120 2125 Leu Leu Lys Thr Ala Leu Arg Pro Asp Met Trp Pro Lys Ser Glu Leu 2130 2135 2140 Lys Leu Gln Trp Phe Asp Lys Leu Leu Met Thr Val Glu Gln Pro Asn 2145 2150 2155 2160 Gln Val Asn Tyr Gly Asn Ile Cys Thr Gly Leu Glu Val Leu Ser Phe 2165 2170 2175 Leu Leu Thr Val Leu Gln Ser Pro Ala Ile Leu Ser Ser Phe Lys Pro 2180 2185 2190 Leu Gln Arg Gly Ile Ala Ala Cys Met Thr Cys Gly Asn Thr Lys Val 2195 2200 2205 Leu Arg Ala Val His Ser Leu Leu Ser Arg Leu Met Ser Ile Phe Pro 2210 2215 2220 Thr Glu Pro Ser Thr Ser Ser Val Ala Ser Lys Tyr Glu Glu Leu Glu 2225 2230 2235 2240 Cys Leu Tyr Ala Ala Val Gly Lys Val Ile Tyr Glu Gly Leu Thr Asn 2245 2250 2255 Tyr Glu Lys Ala Thr Asn Ala Asn Pro Ser Gln Leu Phe Gly Thr Leu 2260 2265 2270 Met Ile Leu Lys Ser Ala Cys Ser Asn Asn Pro Ser Tyr Ile Asp Arg 2275 2280 2285 Leu Ile Ser Val Phe Met Arg Ser Leu Gln Lys Met Val Arg Glu His 2290 2295 2300 Leu Asn Pro Gln Ala Ala Ser Gly Ser Thr Glu Ala Thr Ser Gly Thr 2305 2310 2315 2320 Ser Glu Leu Val Met Leu Ser Leu Glu Leu Val Lys Thr Arg Leu Ala 2325 2330 2335 Val Met Ser Met Glu Met Arg Lys Asn Phe Ile Gln Ala Ile Leu Thr 2340 2345 2350 Ser Leu Ile Glu Lys Ser Pro Asp Ala Lys Ile Leu Arg Ala Val Val 2355 2360 2365 Lys Ile Val Glu Glu Trp Val Lys Asn Asn Ser Pro Met Ala Ala Asn 2370 2375 2380 Gln Thr Pro Thr Leu Arg Glu Lys Ser Ile Leu Leu Val Lys Met Met 2385 2390 2395 2400 Thr Tyr Ile Glu Lys Arg Phe Pro Glu Asp Leu Glu Leu Asn Ala Gln 2405 2410 2415 Phe Leu Asp Leu Val Asn Tyr Val Tyr Arg Asp Glu Thr Leu Ser Gly 2420 2425 2430 Ser Glu Leu Thr Ala Lys Leu Glu Pro Ala Phe Leu Ser Gly Leu Arg 2435 2440 2445 Cys Ala Gln Pro Leu Ile Arg Ala Lys Phe Phe Glu Val Phe Asp Asn 2450 2455 2460 Ser Met Lys Arg Arg Val Tyr Glu Arg Leu Leu Tyr Val Thr Cys Ser 2465 2470 2475 2480 Gln Asn Trp Glu Ala Met Gly Asn His Phe Trp Ile Lys Gln Cys Ile 2485 2490 2495 Glu Leu Leu Leu Ala Val Cys Glu Lys Ser Thr Pro Ile Gly Thr Ser 2500 2505 2510 Cys Gln Gly Ala Met Leu Pro Ser Ile Thr Asn Val Ile Asn Leu Ala 2515 2520 2525 Asp Ser His Asp Arg Ala Ala Phe Ala Met Val Thr His Val Lys Gln 2530 2535 2540 Glu Pro Arg Glu Arg Glu Asn Ser Glu Ser Lys Glu Glu Asp Val Glu 2545 2550 2555 2560 Ile Asp Ile Glu Leu Ala Pro Gly Asp Gln Thr Ser Thr Pro Lys Thr 2565 2570 2575 Lys Glu Leu Ser Glu Lys Asp Ile Gly Asn Gln Leu His Met Leu Thr 2580 2585 2590 Asn Arg His Asp Lys Phe Leu Asp Thr Leu Arg Glu Val Lys Thr Gly 2595 2600 2605 Ala Leu Leu Ser Ala Phe Val Gln Leu Cys His Ile Ser Thr Thr Leu 2610 2615 2620 Ala Glu Lys Thr Trp Val Gln Leu Phe Pro Arg Leu Trp Lys Ile Leu 2625 2630 2635 2640 Ser Asp Arg Gln Gln His Ala Leu Ala Gly Glu Ile Ser Pro Phe Leu 2645 2650 2655 Cys Ser Gly Ser His Gln Val Gln Arg Asp Cys Gln Pro Ser Ala Leu 2660 2665 2670 Asn Cys Phe Val Glu Ala Met Ser Gln Cys Val Pro Pro Ile Pro Ile 2675 2680 2685 Arg Pro Cys Val Leu Lys Tyr Leu Gly Lys Thr His Asn Leu Trp Phe 2690 2695 2700 Arg Ser Thr Leu Met Leu Glu His Gln Ala Phe Glu Lys Gly Leu Ser 2705 2710 2715 2720 Leu Gln Ile Lys Pro Lys Gln Thr Thr Glu Phe Tyr Glu Gln Glu Ser 2725 2730 2735 Ile Thr Pro Pro Gln Gln Glu Ile Leu Asp Ser Leu Ala Glu Leu Tyr 2740 2745 2750 Ser Leu Leu Gln Glu Glu Asp Met Trp Ala Gly Leu Trp Gln Lys Arg 2755 2760 2765 Cys Lys Tyr Ser Glu Thr Ala Thr Ala Ile Ala Tyr Glu Gln His Gly 2770 2775 2780 Phe Phe Glu Gln Ala Gln Glu Ser Tyr Glu Lys Ala Met Asp Lys Ala 2785 2790 2795 2800 Lys Lys Glu His Glu Arg Ser Asn Ala Ser Pro Ala Ile Phe Pro Glu 2805 2810 2815 Tyr Gln Leu Trp Glu Asp His Trp Ile Arg Cys Ser Lys Glu Leu Asn 2820 2825 2830 Gln Trp Glu Ala Leu Thr Glu Tyr Gly Gln Ser Lys Gly His Ile Asn 2835 2840 2845 Pro Tyr Leu Val Leu Glu Cys Ala Trp Arg Val Ser Asn Trp Thr Ala 2850 2855 2860 Met Lys Glu Ala Leu Val Gln Val Glu Val Ser Cys Pro Lys Glu Met 2865 2870 2875 2880 Ala Trp Lys Val Asn Met Tyr Arg Gly Tyr Leu Ala Ile Cys His Pro 2885 2890 2895 Glu Glu Gln Gln Leu Ser Phe Ile Glu Arg Leu Val Glu Met Ala Ser 2900 2905 2910 Ser Leu Ala Ile Arg Glu Trp Arg Arg Leu Pro His Val Val Ser His 2915 2920 2925 Val His Thr Pro Leu Leu Gln Ala Ala Gln Gln Ile Ile Glu Leu Gln 2930 2935 2940 Glu Ala Ala Gln Ile Asn Ala Gly Leu Gln Pro Thr Asn Leu Gly Arg 2945 2950 2955 2960 Asn Asn Ser Leu His Asp Met Lys Thr Val Val Lys Thr Trp Arg Asn 2965 2970 2975 Arg Leu Pro Ile Val Ser Asp Asp Leu Ser His Trp Ser Ser Ile Phe 2980 2985 2990 Met Trp Arg Gln His His Tyr Gln Gly Lys Pro Thr Trp Ser Gly Met 2995 3000 3005 His Ser Ser Ser Ile Val Thr Ala Tyr Glu Asn Ser Ser Gln His Asp 3010 3015 3020 Pro Ser Ser Asn Asn Ala Met Leu Gly Val His Ala Ser Ala Ser Ala 3025 3030 3035 3040 Ile Ile Gln Tyr Gly Lys Ile Ala Arg Lys Gln Gly Leu Val Asn Val 3045 3050 3055 Ala Leu Asp Ile Leu Ser Arg Ile His Thr Ile Pro Thr Val Pro Ile 3060 3065 3070 Val Asp Cys Phe Gln Lys Ile Arg Gln Gln Val Lys Cys Tyr Leu Gln 3075 3080 3085 Leu Ala Gly Val Met Gly Lys Asn Glu Cys Met Gln Gly Leu Glu Val 3090 3095 3100 Ile Glu Ser Thr Asn Leu Lys Tyr Phe Thr Lys Glu Met Thr Ala Glu 3105 3110 3115 3120 Phe Tyr Ala Leu Lys Gly Met Phe Leu Ala Gln Ile Asn Lys Ser Glu 3125 3130 3135 Glu Ala Asn Lys Ala Phe Ser Ala Ala Val Gln Met His Asp Val Leu 3140 3145 3150 Val Lys Ala Trp Ala Met Trp Gly Asp Tyr Leu Glu Asn Ile Phe Val 3155 3160 3165 Lys Glu Arg Gln Leu His Leu Gly Val Ser Ala Ile Thr Cys Tyr Leu 3170 3175 3180 His Ala Cys Arg His Gln Asn Glu Ser Lys Ser Arg Lys Tyr Leu Ala 3185 3190 3195 3200 Lys Val Leu Trp Leu Leu Ser Phe Asp Asp Asp Lys Asn Thr Leu Ala 3205 3210 3215 Asp Ala Val Asp Lys Tyr Cys Ile Gly Val Pro Pro Ile Gln Trp Leu 3220 3225 3230 Ala Trp Ile Pro Gln Leu Leu Thr Cys Leu Val Gly Ser Glu Gly Lys 3235 3240 3245 Leu Leu Leu Asn Leu Ile Ser Gln Val Gly Arg Val Tyr Pro Gln Ala 3250 3255 3260 Val Tyr Phe Pro Ile Arg Thr Leu Tyr Leu Thr Leu Lys Ile Glu Gln 3265 3270 3275 3280 Arg Glu Arg Tyr Lys Ser Asp Pro Gly Pro Ile Arg Ala Thr Ala Pro 3285 3290 3295 Met Trp Arg Cys Ser Arg Ile Met His Met Gln Arg Glu Leu His Pro 3300 3305 3310 Thr Leu Leu Ser Ser Leu Glu Gly Ile Val Asp Gln Met Val Trp Phe 3315 3320 3325 Arg Glu Asn Trp His Glu Glu Val Leu Arg Gln Leu Gln Gln Gly Leu 3330 3335 3340 Ala Lys Cys Tyr Ser Val Ala Phe Glu Lys Ser Gly Ala Val Ser Asp 3345 3350 3355 3360 Ala Lys Ile Thr Pro His Thr Leu Asn Phe Val Lys Lys Leu Val Ser 3365 3370 3375 Thr Phe Gly Val Gly Leu Glu Asn Val Ser Asn Val Ser Thr Met Phe 3380 3385 3390 Ser Ser Ala Ala Ser Glu Ser Leu Ala Arg Arg Ala Gln Ala Thr Ala 3395 3400 3405 Gln Asp Pro Val Phe Gln Lys Leu Lys Gly Gln Phe Thr Thr Asp Phe 3410 3415 3420 Asp Phe Ser Val Pro Gly Ser Met Lys Leu His Asn Leu Ile Ser Lys 3425 3430 3435 3440 Leu Lys Lys Trp Ile Lys Ile Leu Glu Ala Lys Thr Lys Gln Leu Pro 3445 3450 3455 Lys Phe Phe Leu Ile Glu Glu Lys Cys Arg Phe Leu Ser Asn Phe Ser 3460 3465 3470 Ala Gln Thr Ala Glu Val Glu Ile Pro Gly Glu Phe Leu Met Pro Lys 3475 3480 3485 Pro Thr His Tyr Tyr Ile Lys Ile Ala Arg Phe Met Pro Arg Val Glu 3490 3495 3500 Ile Val Gln Lys His Asn Thr Ala Ala Arg Arg Leu Tyr Ile Arg Gly 3505 3510 3515 3520 His Asn Gly Lys Ile Tyr Pro Tyr Leu Val Met Asn Asp Ala Cys Leu 3525 3530 3535 Thr Glu Ser Arg Arg Glu Glu Arg Val Leu Gln Leu Leu Arg Leu Leu 3540 3545 3550 Asn Pro Cys Leu Glu Lys Arg Lys Glu Thr Thr Lys Arg His Leu Phe 3555 3560 3565 Phe Thr Val Pro Arg Val Val Ala Val Ser Pro Gln Met Arg Leu Val 3570 3575 3580 Glu Asp Asn Pro Ser Ser Leu Ser Leu Val Glu Ile Tyr Lys Gln Arg 3585 3590 3595 3600 Cys Ala Lys Lys Gly Ile Glu His Asp Asn Pro Ile Ser Arg Tyr Tyr 3605 3610 3615 Asp Arg Leu Ala Thr Val Gln Ala Arg Gly Thr Gln Ala Ser His Gln 3620 3625 3630 Val Leu Arg Asp Ile Leu Lys Glu Val Gln Ser Asn Met Val Pro Arg 3635 3640 3645 Ser Met Leu Lys Glu Trp Ala Leu His Thr Phe Pro Asn Ala Thr Asp 3650 3655 3660 Tyr Trp Thr Phe Arg Lys Met Phe Thr Ile Gln Leu Ala Leu Ile Gly 3665 3670 3675 3680 Phe Ala Glu Phe Val Leu His Leu Asn Arg Leu Asn Pro Glu Met Leu 3685 3690 3695 Gln Ile Ala Gln Asp Thr Gly Lys Leu Asn Val Ala Tyr Phe Arg Phe 3700 3705 3710 Asp Ile Asn Asp Ala Thr Gly Asp Leu Asp Ala Asn Arg Pro Val Pro 3715 3720 3725 Phe Arg Leu Thr Pro Asn Ile Ser Glu Phe Leu Thr Thr Ile Gly Val 3730 3735 3740 Ser Gly Pro Leu Thr Ala Ser Met Ile Ala Val Ala Arg Cys Phe Ala 3745 3750 3755 3760 Gln Pro Asn Phe Lys Val Asp Gly Ile Leu Lys Thr Val Leu Arg Asp 3765 3770 3775 Glu Ile Ile Ala Trp His Lys Lys Thr Gln Glu Asp Thr Ser Ser Pro 3780 3785 3790 Leu Ser Ala Ala Gly Gln Pro Glu Asn Met Asp Ser Gln Gln Leu Val 3795 3800 3805 Ser Leu Val Gln Lys Ala Val Thr Ala Ile Met Thr Arg Leu His Asn 3810 3815 3820 Leu Ala Gln Phe Glu Gly Gly Glu Ser Lys Val Asn Thr Leu Val Ala 3825 3830 3835 3840 Ala Ala Asn Ser Leu Asp Asn Leu Cys Arg Met Asp Pro Ala Trp His 3845 3850 3855 Pro Trp Leu <210> 94 <211> 1508 <212> PRT <213> Homo sapiens <400> 94 Met Phe Ser Ala Leu Lys Tyr His Ala Ile Asp Tyr Leu Tyr Glu Asn 1 5 10 15 Val Val Arg Lys Lys Phe Tyr Arg Asp Ala Leu Leu Leu Arg Ile Pro 20 25 30 Ser Cys Leu Tyr Gln Asp Glu Ser Tyr His Val Ala Val Thr Asp Asn 35 40 45 Lys Phe Arg Arg Pro Trp Thr Arg Val Ser Ala Val Ser Val Pro Gly 50 55 60 Met Thr Asp Thr Ser Val Leu Asp Gln Trp Lys Ala Ser Phe Phe Val 65 70 75 80 Glu Asp Phe Leu Glu Lys Lys Thr Ile Thr Arg Met Val Thr Gln Ile 85 90 95 Asn Cys Glu Phe Glu Glu Val Val Pro Ser Ser Asn Pro Asp Ser Gln 100 105 110 Ile Glu Val Glu Glu Val Ser Leu Tyr Thr His Met Asp Tyr Asn Glu 115 120 125 Val Phe Thr Pro Val Ser Cys Leu Glu Lys Cys Ser Ala Leu Gln Asn 130 135 140 Gln Asn Gln Asp Leu Phe Ile Asp Asp Lys Gly Ile Leu Phe Val Ser 145 150 155 160 Ser Arg Lys His Leu Pro Thr Leu Pro Thr Leu Leu Ser Arg Leu Lys 165 170 175 Leu Phe Leu Val Lys Asp Pro Leu Leu Asp Phe Lys Gly Gln Ile Phe 180 185 190 Thr Glu Ala Asn Phe Ser Arg Glu Cys Phe Ser Leu Gln Glu Thr Leu 195 200 205 Glu Ala Phe Val Lys Glu Asp Phe Cys Met Asp Lys Val Asn Phe Cys 210 215 220 Gln Glu Lys Leu Glu Asp Thr Ile Cys Leu Asn Glu Pro Ser Ser Phe 225 230 235 240 Leu Ile Glu Tyr Glu Phe Leu Ile Pro Pro Ser Leu Lys Pro Glu Ile 245 250 255 Asp Ile Pro Ser Leu Ser Glu Leu Lys Glu Leu Leu Asn Pro Val Pro 260 265 270 Glu Ile Ile Asn Tyr Val Asp Glu Lys Glu Lys Leu Phe Glu Arg Asp 275 280 285 Leu Thr Asn Lys His Gly Ile Glu Asp Ile Gly Asp Ile Lys Phe Ser 290 295 300 Ser Thr Glu Ile Leu Thr Ile Gln Ser Gln Ser Glu Pro Glu Glu Cys 305 310 315 320 Ser Lys Pro Gly Glu Leu Glu Met Pro Leu Thr Pro Leu Phe Leu Thr 325 330 335 Cys Gln His Ser Ser Val Asn Ser Leu Arg Thr Glu Leu Gln Thr Phe 340 345 350 Pro Leu Ser Pro Val Cys Lys Ile Asn Leu Leu Thr Ala Glu Glu Ser 355 360 365 Ala Asn Glu Tyr Tyr Met Met Trp Gln Leu Glu Arg Cys Arg Ser Pro 370 375 380 Leu Asn Pro Phe Leu Leu Thr Val Pro Arg Ile Gln Glu Pro His Ser 385 390 395 400 Gln Tyr Ser Val Thr Asp Leu Lys Lys Ile Phe Ser Val Lys Glu Glu 405 410 415 Ser Leu Val Ile Asn Leu Glu Lys Ala Glu Trp Trp Lys Gln Ala Gly 420 425 430 Leu Asn Leu Lys Met Met Glu Thr Leu Glu His Leu Asn Thr Tyr Leu 435 440 445 Cys His Asp Asn Leu Ser Ser Asn Asp Thr Lys Ile Glu Ile Phe Leu 450 455 460 Pro Thr Lys Val Leu Gln Leu Glu Ser Cys Leu Glu His Lys Ser Arg 465 470 475 480 Ser Ser Pro Ile Ala Leu Ile Asp Glu Lys Ser Thr Asn Ala His Leu 485 490 495 Ser Leu Pro Gln Lys Ser Pro Ser Leu Ala Lys Glu Val Pro Asp Leu 500 505 510 Cys Phe Ser Asp Asp Tyr Phe Ser Asp Lys Gly Ala Ala Lys Glu Glu 515 520 525 Lys Pro Lys Asn Asp Gln Glu Pro Val Asn Arg Ile Ile Gln Lys Lys 530 535 540 Glu Asn Asn Asp His Phe Glu Leu Asp Cys Thr Gly Pro Ser Ile Lys 545 550 555 560 Ser Pro Ser Ser Ser Ile Ile Lys Lys Ala Ser Phe Glu His Gly Lys 565 570 575 Lys Gln Glu Asn Asp Leu Asp Leu Leu Ser Asp Phe Ile Met Leu Arg 580 585 590 Asn Lys Tyr Lys Thr Cys Thr Ser Lys Thr Glu Val Thr Asn Ser Asp 595 600 605 Glu Lys His Asp Lys Glu Ala Cys Ser Leu Thr Leu Gln Glu Glu Ser 610 615 620 Pro Ile Val His Ile Asn Lys Thr Leu Glu Glu Ile Asn Gln Glu Arg 625 630 635 640 Gly Thr Asp Ser Val Ile Glu Ile Gln Ala Ser Asp Ser Gln Cys Gln 645 650 655 Ala Phe Cys Leu Leu Glu Ala Ala Ala Ser Pro Ile Leu Lys Asn Leu 660 665 670 Val Ser Leu Cys Thr Leu Pro Thr Ala Asn Trp Lys Phe Ala Thr Val 675 680 685 Ile Phe Asp Gln Thr Arg Phe Leu Leu Lys Glu Gln Glu Lys Val Val 690 695 700 Ser Asp Ala Val Arg Gln Gly Thr Ile Asp Glu Arg Glu Met Thr Phe 705 710 715 720 Lys His Ala Ala Leu Leu His Leu Leu Val Thr Ile Arg Asp Val Leu 725 730 735 Leu Thr Cys Ser Leu Asp Thr Ala Leu Gly Tyr Leu Ser Lys Ala Lys 740 745 750 Asp Ile Tyr Asn Ser Ile Leu Gly Pro Tyr Leu Gly Asp Ile Trp Arg 755 760 765 Gln Leu Glu Ile Val Gln Phe Ile Arg Gly Lys Lys Pro Glu Thr Asn 770 775 780 Tyr Lys Ile Gln Glu Leu Gln Cys Gln Ile Leu Ser Trp Met Gln Ser 785 790 795 800 Gln Gln Gln Ile Lys Val Leu Ile Ile Ile Arg Met Asp Ser Asp Gly 805 810 815 Glu Lys His Phe Leu Ile Lys Ile Leu Asn Lys Ile Glu Gly Leu Thr 820 825 830 Leu Thr Val Leu His Ser Asn Glu Arg Lys Asp Phe Leu Glu Ser Glu 835 840 845 Gly Val Leu Arg Gly Thr Ser Ser Cys Val Val Val His Asn Gln Tyr 850 855 860 Ile Gly Ala Asp Phe Pro Trp Ser Asn Phe Ser Phe Val Val Glu Tyr 865 870 875 880 Asn Tyr Val Glu Asp Ser Cys Trp Thr Lys His Cys Lys Glu Leu Asn 885 890 895 Ile Pro Tyr Met Ala Phe Lys Val Ile Leu Pro Asp Thr Val Leu Glu 900 905 910 Arg Ser Thr Leu Leu Asp Arg Phe Gly Gly Phe Leu Leu Glu Ile Gln 915 920 925 Ile Pro Tyr Val Phe Phe Ala Ser Glu Gly Leu Leu Asn Thr Pro Asp 930 935 940 Ile Leu Gln Leu Leu Glu Ser Asn Tyr Asn Ile Ser Leu Val Glu Arg 945 950 955 960 Gly Cys Ser Glu Ser Leu Lys Leu Phe Gly Ser Ser Glu Cys Tyr Val 965 970 975 Val Val Thr Ile Asp Glu His Thr Ala Ile Ile Leu Gln Asp Leu Glu 980 985 990 Glu Leu Asn Cys Glu Lys Ala Ser Asp Asn Ile Ile Met Arg Leu Met 995 1000 1005 Ala Leu Ser Leu Gln Tyr Arg Tyr Cys Trp Ile Ile Leu Tyr Thr Lys 1010 1015 1020 Glu Thr Leu Asn Ser Glu Tyr Pro Leu Thr Glu Lys Thr Leu His His 1025 1030 1035 1040 Leu Ala Leu Ile Tyr Ala Ala Leu Val Ser Phe Gly Leu Asn Ser Glu 1045 1050 1055 Glu Leu Asp Val Lys Leu Ile Ile Ala Pro Gly Val Glu Ala Thr Ala 1060 1065 1070 Leu Ile Ile Arg Gln Ile Ala Asp His Ser Leu Met Thr Ser Lys Arg 1075 1080 1085 Asp Pro His Glu Trp Leu Asp Lys Ser Trp Leu Lys Val Ser Pro Ser 1090 1095 1100 Glu Glu Glu Met Tyr Leu Leu Asp Phe Pro Cys Ile Asn Pro Leu Val 1105 1110 1115 1120 Ala Gln Leu Met Leu Asn Lys Gly Pro Ser Leu His Trp Ile Leu Leu 1125 1130 1135 Ala Thr Leu Cys Gln Leu Gln Glu Leu Leu Pro Glu Val Pro Glu Lys 1140 1145 1150 Val Leu Lys His Phe Cys Ser Ile Thr Ser Leu Phe Lys Ile Gly Ser 1155 1160 1165 Ser Ser Ile Thr Lys Ser Pro Gln Ile Ser Ser Pro Gln Glu Asn Arg 1170 1175 1180 Asn Gln Ile Ser Thr Leu Ser Ser Gln Ser Ser Ala Ser Asp Leu Asp 1185 1190 1195 1200 Ser Val Ile Gln Glu His Asn Glu Tyr Tyr Gln Tyr Leu Gly Leu Gly 1205 1210 1215 Glu Thr Val Gln Glu Asp Lys Thr Thr Thr Leu Asn Asp Asn Ser Ser 1220 1225 1230 Ile Met Glu Leu Lys Gly Ile Ser Ser Phe Leu Pro Pro Val Thr Ser 1235 1240 1245 Tyr Asn Gln Thr Ser Tyr Trp Lys Asp Ser Ser Cys Lys Ser Asn Ile 1250 1255 1260 Gly Gln Asn Thr Pro Phe Leu Ile Asn Ile Glu Ser Arg Arg Pro Ala 1265 1270 1275 1280 Tyr Asn Ser Phe Leu Asn His Ser Asp Ser Glu Ser Asp Val Phe Ser 1285 1290 1295 Leu Gly Leu Thr Gln Met Asn Cys Glu Thr Ile Lys Ser Pro Thr Asp 1300 1305 1310 Thr Gln Lys Arg Val Ser Val Val Pro Arg Phe Ile Asn Ser Gln Lys 1315 1320 1325 Arg Arg Thr His Glu Ala Lys Gly Phe Ile Asn Lys Asp Val Ser Asp 1330 1335 1340 Pro Ile Phe Ser Leu Glu Gly Thr Gln Ser Pro Leu His Trp Asn Phe 1345 1350 1355 1360 Lys Lys Asn Ile Trp Glu Gln Glu Asn His Pro Phe Asn Leu Gln Tyr 1365 1370 1375 Gly Ala Gln Gln Thr Ala Cys Asn Lys Leu Tyr Ser Gln Lys Gly Asn 1380 1385 1390 Leu Phe Thr Asp Gln Gln Lys Cys Leu Ser Asp Glu Ser Glu Gly Leu 1395 1400 1405 Thr Cys Glu Ser Ser Lys Asp Glu Thr Phe Trp Arg Glu Leu Pro Ser 1410 1415 1420 Val Pro Ser Leu Asp Leu Phe Arg Ala Ser Asp Ser Asn Ala Asn Gln 1425 1430 1435 1440 Lys Glu Phe Asn Ser Leu Tyr Phe Tyr Gln Arg Ala Gly Lys Ser Leu 1445 1450 1455 Gly Gln Lys Arg His His Glu Ser Ser Phe Asn Ser Gly Asp Lys Glu 1460 1465 1470 Ser Leu Thr Gly Phe Met Cys Ser Gln Leu Pro Gln Phe Lys Lys Arg 1475 1480 1485 Arg Leu Ala Tyr Glu Lys Val Pro Gly Arg Val Asp Gly Gln Thr Arg 1490 1495 1500 Leu Arg Phe Phe 1505 <210> 95 <211> 583 <212> PRT <213> Homo sapiens <400> 95 Met Ala Leu Lys Lys Ser Ser Pro Ser Leu Asp Ser Gly Asp Ser Asp 1 5 10 15 Ser Glu Glu Leu Pro Thr Phe Ala Phe Leu Lys Lys Glu Pro Ser Ser 20 25 30 Thr Lys Arg Arg Gln Pro Glu Arg Glu Glu Lys Ile Val Val Val Asp 35 40 45 Ile Ser Asp Cys Glu Ala Ser Cys Pro Pro Ala Pro Glu Leu Phe Ser 50 55 60 Pro Pro Val Pro Glu Ile Ala Glu Thr Val Thr Gln Thr Gln Pro Val 65 70 75 80 Arg Leu Leu Ser Ser Glu Ser Glu Asp Glu Glu Glu Phe Ile Pro Leu 85 90 95 Ala Gln Arg Leu Thr Cys Lys Phe Leu Thr His Lys Gln Leu Ser Pro 100 105 110 Glu Asp Ser Ser Ser Pro Val Lys Ser Val Leu Asp His Gln Asn Asn 115 120 125 Glu Gly Ala Ser Cys Asp Trp Lys Lys Pro Phe Pro Lys Ile Pro Glu 130 135 140 Val Pro Leu His Asp Thr Pro Glu Arg Ser Ala Ala Asp Asn Lys Asp 145 150 155 160 Leu Ile Leu Asp Pro Cys Cys Gln Leu Pro Ala Tyr Leu Ser Thr Cys 165 170 175 Pro Gly Gln Ser Ser Ser Leu Ala Val Thr Lys Thr Asn Ser Asp Ile 180 185 190 Leu Pro Pro Gln Lys Lys Thr Lys Pro Ser Gln Lys Val Gln Gly Arg 195 200 205 Gly Ser His Gly Cys Arg Gln Gln Arg Gln Ala Arg Gln Lys Glu Ser 210 215 220 Thr Leu Arg Arg Gln Glu Arg Lys Asn Ala Ala Leu Val Thr Arg Met 225 230 235 240 Lys Ala Gln Arg Pro Glu Glu Cys Leu Lys His Ile Ile Val Val Leu 245 250 255 Asp Pro Val Leu Leu Gln Met Glu Gly Gly Gly Gln Leu Leu Gly Ala 260 265 270 Leu Gln Thr Met Glu Cys Arg Cys Val Ile Glu Ala Gln Ala Val Pro 275 280 285 Cys Ser Val Thr Trp Arg Arg Arg Ala Gly Pro Ser Glu Asp Arg Glu 290 295 300 Asp Trp Val Glu Glu Pro Thr Val Leu Val Leu Leu Arg Ala Glu Ala 305 310 315 320 Phe Val Ser Met Ile Asp Asn Gly Lys Gln Gly Ser Leu Asp Ser Thr 325 330 335 Met Lys Gly Lys Glu Thr Leu Gln Gly Phe Val Thr Asp Ile Thr Ala 340 345 350 Lys Thr Ala Gly Lys Ala Leu Ser Leu Val Ile Val Asp Gln Glu Lys 355 360 365 Cys Phe Ser Leu Glu Leu Leu Phe Phe Asp Phe Leu Pro Cys Thr Ser 370 375 380 Ala Gln Asn Pro Pro Arg Arg Gly Lys Gln Gly Ala Asn Lys Gln Thr 385 390 395 400 Lys Lys Gln Gln Gln Arg Gln Pro Glu Ala Ser Ile Gly Ser Met Val 405 410 415 Ser Arg Val Asp Ala Glu Glu Ala Leu Val Asp Leu Gln Leu His Thr 420 425 430 Glu Ala Gln Ala Gln Ile Val Gln Ser Trp Lys Glu Leu Ala Asp Phe 435 440 445 Thr Cys Ala Phe Thr Lys Ala Val Ala Glu Ala Pro Phe Lys Lys Leu 450 455 460 Arg Asp Glu Thr Thr Phe Ser Phe Cys Leu Glu Ser Asp Trp Ala Gly 465 470 475 480 Gly Val Lys Val Asp Leu Ala Gly Arg Gly Leu Ala Leu Val Trp Arg 485 490 495 Arg Gln Ile Gln Gln Leu Asn Arg Val Ser Leu Glu Met Ala Ser Ala 500 505 510 Val Val Asn Ala Tyr Pro Ser Pro Gln Leu Leu Val Gln Ala Tyr Gln 515 520 525 Gln Cys Phe Ser Asp Lys Glu Arg Gln Asn Leu Leu Ala Asp Ile Gln 530 535 540 Val Arg Arg Gly Glu Gly Val Thr Ser Thr Ser Arg Arg Ile Gly Pro 545 550 555 560 Glu Leu Ser Arg Arg Ile Tyr Leu Gln Met Thr Thr Leu Gln Pro His 565 570 575 Leu Ser Leu Asp Ser Ala Asp 580 <210> 96 <211> 8749 <212> PRT <213> Homo sapiens <400> 96 Met Ala Thr Ser Arg Gly Ala Ser Arg Cys Pro Arg Asp Ile Ala Asn 1 5 10 15 Val Met Gln Arg Leu Gln Asp Glu Gln Glu Ile Val Gln Lys Arg Thr 20 25 30 Phe Thr Lys Trp Ile Asn Ser His Leu Ala Lys Arg Lys Pro Pro Met 35 40 45 Val Val Asp Asp Leu Phe Glu Asp Met Lys Asp Gly Val Lys Leu Leu 50 55 60 Ala Leu Leu Glu Val Leu Ser Gly Gln Lys Leu Pro Cys Glu Gln Gly 65 70 75 80 Arg Arg Met Lys Arg Ile His Ala Val Ala Asn Ile Gly Thr Ala Leu 85 90 95 Lys Phe Leu Glu Gly Arg Lys Ser Met His Arg Gly Ser Pro Ile Lys 100 105 110 Leu Val Asn Ile Asn Ser Thr Asp Ile Ala Asp Gly Arg Pro Ser Ile 115 120 125 Val Leu Gly Leu Met Trp Thr Ile Ile Leu Tyr Phe Gln Ile Glu Glu 130 135 140 Leu Thr Ser Asn Leu Pro Gln Leu Gln Ser Leu Ser Ser Ser Ala Ser 145 150 155 160 Ser Val Asp Ser Ile Val Ser Ser Glu Thr Pro Ser Pro Pro Ser Lys 165 170 175 Arg Lys Val Thr Thr Lys Ile Gln Gly Asn Ala Lys Lys Ala Leu Leu 180 185 190 Lys Trp Val Gln Tyr Thr Ala Gly Lys Gln Thr Gly Ile Glu Val Lys 195 200 205 Asp Phe Gly Lys Ser Trp Arg Ser Gly Val Ala Phe His Ser Val Ile 210 215 220 His Ala Ile Arg Pro Glu Leu Val Asp Leu Glu Thr Val Lys Gly Arg 225 230 235 240 Ser Asn Arg Glu Asn Leu Glu Asp Ala Phe Thr Ile Ala Glu Thr Glu 245 250 255 Leu Gly Ile Pro Arg Leu Leu Asp Pro Glu Asp Val Asp Val Asp Lys 260 265 270 Pro Asp Glu Lys Ser Ile Met Thr Tyr Val Ala Gln Phe Leu Lys His 275 280 285 Tyr Pro Asp Ile His Asn Ala Ser Thr Asp Gly Gln Glu Asp Asp Glu 290 295 300 Ile Leu Pro Gly Phe Pro Ser Phe Ala Asn Ser Val Gln Asn Phe Lys 305 310 315 320 Arg Glu Asp Arg Val Ile Phe Lys Glu Met Lys Val Trp Ile Glu Gln 325 330 335 Phe Glu Arg Asp Leu Thr Arg Ala Gln Met Val Glu Ser Asn Leu Gln 340 345 350 Asp Lys Tyr Gln Ser Phe Lys His Phe Arg Val Gln Tyr Glu Met Lys 355 360 365 Arg Lys Gln Ile Glu His Leu Ile Gln Pro Leu His Arg Asp Gly Lys 370 375 380 Leu Ser Leu Asp Gln Ala Leu Val Lys Gln Ser Trp Asp Arg Val Thr 385 390 395 400 Ser Arg Leu Phe Asp Trp His Ile Gln Leu Asp Lys Ser Leu Pro Ala 405 410 415 Pro Leu Gly Thr Ile Gly Ala Trp Leu Tyr Arg Ala Glu Val Ala Leu 420 425 430 Arg Glu Glu Ile Thr Val Gln Gln Val His Glu Glu Thr Ala Asn Thr 435 440 445 Ile Gln Arg Lys Leu Glu Gln His Lys Asp Leu Leu Gln Asn Thr Asp 450 455 460 Ala His Lys Arg Ala Phe His Glu Ile Tyr Arg Thr Arg Ser Val Asn 465 470 475 480 Gly Ile Pro Val Pro Pro Asp Gln Leu Glu Asp Met Ala Glu Arg Phe 485 490 495 His Phe Val Ser Ser Thr Ser Glu Leu His Leu Met Lys Met Glu Phe 500 505 510 Leu Glu Leu Lys Tyr Arg Leu Leu Ser Leu Leu Val Leu Ala Glu Ser 515 520 525 Lys Leu Lys Ser Trp Ile Ile Lys Tyr Gly Arg Arg Glu Ser Val Glu 530 535 540 Gln Leu Leu Gln Asn Tyr Val Ser Phe Ile Glu Asn Ser Lys Phe Phe 545 550 555 560 Glu Gln Tyr Glu Val Thr Tyr Gln Ile Leu Lys Gln Thr Ala Glu Met 565 570 575 Tyr Val Lys Ala Asp Gly Ser Val Glu Glu Ala Glu Asn Val Met Lys 580 585 590 Phe Met Asn Glu Thr Thr Ala Gln Trp Arg Asn Leu Ser Val Glu Val 595 600 605 Arg Ser Val Arg Ser Met Leu Glu Glu Val Ile Ser Asn Trp Asp Arg 610 615 620 Tyr Gly Asn Thr Val Ala Ser Leu Gln Ala Trp Leu Glu Asp Ala Glu 625 630 635 640 Lys Met Leu Asn Gln Ser Glu Asn Ala Lys Lys Asp Phe Phe Arg Asn 645 650 655 Leu Pro His Trp Ile Gln Gln His Thr Ala Met Asn Asp Ala Gly Asn 660 665 670 Phe Leu Ile Glu Thr Cys Asp Glu Met Val Ser Arg Asp Leu Lys Gln 675 680 685 Gln Leu Leu Leu Leu Asn Gly Arg Trp Arg Glu Leu Phe Met Glu Val 690 695 700 Lys Gln Tyr Ala Gln Ala Asp Glu Met Asp Arg Met Lys Lys Glu Tyr 705 710 715 720 Thr Asp Cys Val Val Thr Leu Ser Ala Phe Ala Thr Glu Ala His Lys 725 730 735 Lys Leu Ser Glu Pro Leu Glu Val Ser Phe Met Asn Val Lys Leu Leu 740 745 750 Ile Gln Asp Leu Glu Asp Ile Glu Gln Arg Val Pro Val Met Asp Ala 755 760 765 Gln Tyr Lys Ile Ile Thr Lys Thr Ala His Leu Ile Thr Lys Glu Ser 770 775 780 Pro Gln Glu Glu Gly Lys Glu Met Phe Ala Thr Met Ser Lys Leu Lys 785 790 795 800 Glu Gln Leu Thr Lys Val Lys Glu Cys Tyr Ser Pro Leu Leu Tyr Glu 805 810 815 Ser Gln Gln Leu Leu Ile Pro Leu Glu Glu Leu Glu Lys Gln Met Thr 820 825 830 Ser Phe Tyr Asp Ser Leu Gly Lys Ile Asn Glu Ile Ile Thr Val Leu 835 840 845 Glu Arg Glu Ala Gln Ser Ser Ala Leu Phe Lys Gln Lys His Gln Glu 850 855 860 Leu Leu Ala Cys Gln Glu Asn Cys Lys Lys Thr Leu Thr Leu Ile Glu 865 870 875 880 Lys Gly Ser Gln Ser Val Gln Lys Phe Val Thr Leu Ser Asn Val Leu 885 890 895 Lys His Phe Asp Gln Thr Arg Leu Gln Arg Gln Ile Ala Asp Ile His 900 905 910 Val Ala Phe Gln Ser Met Val Lys Lys Thr Gly Asp Trp Lys Lys His 915 920 925 Val Glu Thr Asn Ser Arg Leu Met Lys Lys Phe Glu Glu Ser Arg Ala 930 935 940 Glu Leu Glu Lys Val Leu Arg Ile Ala Gln Glu Gly Leu Glu Glu Lys 945 950 955 960 Gly Asp Pro Glu Glu Leu Leu Arg Arg His Thr Glu Phe Phe Ser Gln 965 970 975 Leu Asp Gln Arg Val Leu Asn Ala Phe Leu Lys Ala Cys Asp Glu Leu 980 985 990 Thr Asp Ile Leu Pro Glu Gln Glu Gln Gln Gly Leu Gln Glu Ala Val 995 1000 1005 Arg Lys Leu His Lys Gln Trp Lys Asp Leu Gln Gly Glu Ala Pro Tyr 1010 1015 1020 His Leu Leu His Leu Lys Ile Asp Val Glu Lys Asn Arg Phe Leu Ala 1025 1030 1035 1040 Ser Val Glu Glu Cys Arg Thr Glu Leu Asp Arg Glu Thr Lys Leu Met 1045 1050 1055 Pro Gln Glu Gly Ser Glu Lys Ile Ile Lys Glu His Arg Val Phe Phe 1060 1065 1070 Ser Asp Lys Gly Pro His His Leu Cys Glu Lys Arg Leu Gln Leu Ile 1075 1080 1085 Glu Glu Leu Cys Val Lys Leu Pro Val Arg Asp Pro Val Arg Asp Thr 1090 1095 1100 Pro Gly Thr Cys His Val Thr Leu Lys Glu Leu Arg Ala Ala Ile Asp 1105 1110 1115 1120 Ser Thr Tyr Arg Lys Leu Met Glu Asp Pro Asp Lys Trp Lys Asp Tyr 1125 1130 1135 Thr Ser Arg Phe Ser Glu Phe Ser Ser Trp Ile Ser Thr Asn Glu Thr 1140 1145 1150 Gln Leu Lys Gly Ile Lys Gly Glu Ala Ile Asp Thr Ala Asn His Gly 1155 1160 1165 Glu Val Lys Arg Ala Val Glu Glu Ile Arg Asn Gly Val Thr Lys Arg 1170 1175 1180 Gly Glu Thr Leu Ser Trp Leu Lys Ser Arg Leu Lys Val Leu Thr Glu 1185 1190 1195 1200 Val Ser Ser Glu Asn Glu Ala Gln Lys Gln Gly Asp Glu Leu Ala Lys 1205 1210 1215 Leu Ser Ser Ser Phe Lys Ala Leu Val Thr Leu Leu Ser Glu Val Glu 1220 1225 1230 Lys Met Leu Ser Asn Phe Gly Asp Cys Val Gln Tyr Lys Glu Ile Val 1235 1240 1245 Lys Asn Ser Leu Glu Glu Leu Ile Ser Gly Ser Lys Glu Val Gln Glu 1250 1255 1260 Gln Ala Glu Lys Ile Leu Asp Thr Glu Asn Leu Phe Glu Ala Gln Gln 1265 1270 1275 1280 Leu Leu Leu His His Gln Gln Lys Thr Lys Arg Ile Ser Ala Lys Lys 1285 1290 1295 Arg Asp Val Gln Gln Gln Ile Ala Gln Ala Gln Gln Gly Glu Gly Gly 1300 1305 1310 Leu Pro Asp Arg Gly His Glu Glu Leu Arg Lys Leu Glu Ser Thr Leu 1315 1320 1325 Asp Gly Leu Glu Arg Ser Arg Glu Arg Gln Glu Arg Arg Ile Gln Val 1330 1335 1340 Thr Leu Arg Lys Trp Glu Arg Phe Glu Thr Asn Lys Glu Thr Val Val 1345 1350 1355 1360 Arg Tyr Leu Phe Gln Thr Gly Ser Ser His Glu Arg Phe Leu Ser Phe 1365 1370 1375 Ser Ser Leu Glu Ser Leu Ser Ser Glu Leu Glu Gln Thr Lys Glu Phe 1380 1385 1390 Ser Lys Arg Thr Glu Ser Ile Ala Val Gln Ala Glu Asn Leu Val Lys 1395 1400 1405 Glu Ala Ser Glu Ile Pro Leu Gly Pro Gln Asn Lys Gln Leu Leu Gln 1410 1415 1420 Gln Gln Ala Lys Ser Ile Lys Glu Gln Val Lys Lys Leu Glu Asp Thr 1425 1430 1435 1440 Leu Glu Glu Asp Ile Lys Thr Met Glu Met Val Lys Thr Lys Trp Asp 1445 1450 1455 His Phe Gly Ser Asn Phe Glu Thr Leu Ser Val Trp Ile Thr Glu Lys 1460 1465 1470 Glu Lys Glu Leu Asn Ala Leu Glu Thr Ser Ser Ser Ala Met Asp Met 1475 1480 1485 Gln Ile Ser Gln Ile Lys Val Thr Ile Gln Glu Ile Glu Ser Lys Leu 1490 1495 1500 Ser Ser Ile Val Gly Leu Glu Glu Glu Ala Gln Ser Phe Ala Gln Phe 1505 1510 1515 1520 Val Thr Thr Gly Glu Ser Ala Arg Ile Lys Ala Lys Leu Thr Gln Ile 1525 1530 1535 Arg Arg Tyr Gly Glu Glu Leu Arg Glu His Ala Gln Cys Leu Glu Gly 1540 1545 1550 Thr Ile Leu Gly His Leu Ser Gln Gln Gln Lys Phe Glu Glu Asn Leu 1555 1560 1565 Arg Lys Ile Gln Gln Ser Val Ser Glu Phe Glu Asp Lys Leu Ala Val 1570 1575 1580 Pro Ile Lys Ile Cys Ser Ser Ala Thr Glu Thr Tyr Lys Val Leu Gln 1585 1590 1595 1600 Glu His Met Asp Leu Cys Gln Ala Leu Glu Ser Leu Ser Ser Ala Ile 1605 1610 1615 Thr Ala Phe Ser Ala Ser Ala Arg Lys Val Val Asn Arg Asp Ser Cys 1620 1625 1630 Val Gln Glu Ala Ala Ala Leu Gln Gln Gln Tyr Glu Asp Ile Leu Arg 1635 1640 1645 Arg Ala Lys Glu Arg Gln Thr Ala Leu Glu Asn Leu Leu Ala His Trp 1650 1655 1660 Gln Arg Leu Glu Lys Glu Leu Ser Ser Phe Leu Thr Trp Leu Glu Arg 1665 1670 1675 1680 Gly Glu Ala Lys Ala Ser Ser Pro Glu Met Asp Ile Ser Ala Asp Arg 1685 1690 1695 Val Lys Val Glu Gly Glu Leu Gln Leu Ile Gln Ala Leu Gln Asn Glu 1700 1705 1710 Val Val Ser Gln Ala Ser Phe Tyr Ser Lys Leu Leu Gln Leu Lys Glu 1715 1720 1725 Ser Leu Phe Ser Val Ala Ser Lys Asp Asp Val Lys Met Met Lys Leu 1730 1735 1740 His Leu Glu Gln Leu Asp Glu Arg Trp Arg Asp Leu Pro Gln Ile Ile 1745 1750 1755 1760 Asn Lys Arg Ile Asn Phe Leu Gln Ser Val Val Ala Glu His Gln Gln 1765 1770 1775 Phe Asp Glu Leu Leu Leu Ser Phe Ser Val Trp Ile Lys Leu Phe Leu 1780 1785 1790 Ser Glu Leu Gln Thr Thr Ser Glu Ile Ser Ile Met Asp His Gln Val 1795 1800 1805 Ala Leu Thr Arg His Lys Asp His Ala Ala Glu Val Glu Ser Lys Lys 1810 1815 1820 Gly Glu Leu Gln Ser Leu Gln Gly His Leu Ala Lys Leu Gly Ser Leu 1825 1830 1835 1840 Gly Arg Ala Glu Asp Leu His Leu Leu Gln Gly Lys Ala Glu Asp Cys 1845 1850 1855 Phe Gln Leu Phe Glu Glu Ala Ser Gln Val Val Glu Arg Arg Gln Leu 1860 1865 1870 Ala Leu Ser His Leu Ala Glu Phe Leu Gln Ser His Ala Ser Leu Ser 1875 1880 1885 Gly Ile Leu Arg Gln Leu Arg Gln Thr Val Glu Ala Thr Asn Ser Met 1890 1895 1900 Asn Lys Asn Glu Ser Asp Leu Ile Glu Lys Asp Leu Asn Asp Ala Leu 1905 1910 1915 1920 Gln Asn Ala Lys Ala Leu Glu Ser Ala Ala Val Ser Leu Asp Gly Ile 1925 1930 1935 Leu Ser Lys Ala Gln Tyr His Leu Lys Ile Gly Ser Ser Glu Gln Arg 1940 1945 1950 Thr Ser Cys Arg Ala Thr Ala Asp Gln Leu Cys Gly Glu Val Glu Arg 1955 1960 1965 Ile Gln Asn Leu Leu Gly Thr Lys Gln Ser Glu Ala Asp Ala Leu Ala 1970 1975 1980 Val Leu Lys Lys Ala Phe Gln Asp Gln Lys Glu Glu Leu Leu Lys Ser 1985 1990 1995 2000 Ile Glu Asp Ile Glu Glu Arg Thr Asp Lys Glu Arg Leu Lys Glu Pro 2005 2010 2015 Thr Arg Gln Ala Leu Gln Gln Arg Leu Arg Val Phe Asn Gln Leu Glu 2020 2025 2030 Asp Glu Leu Asn Ser His Glu His Glu Leu Cys Trp Leu Lys Asp Lys 2035 2040 2045 Ala Lys Gln Ile Ala Gln Lys Asp Val Ala Phe Ala Pro Glu Val Asp 2050 2055 2060 Arg Glu Ile Asn Arg Leu Glu Val Thr Trp Asp Asp Thr Lys Arg Leu 2065 2070 2075 2080 Ile His Glu Asn Gln Gly Gln Cys Cys Gly Leu Ile Asp Leu Met Arg 2085 2090 2095 Glu Tyr Gln Asn Leu Lys Ser Ala Val Ser Lys Val Leu Glu Asn Ala 2100 2105 2110 Ser Ser Val Ile Val Thr Arg Thr Thr Ile Lys Asp Gln Glu Asp Leu 2115 2120 2125 Lys Trp Ala Phe Ser Lys His Glu Thr Ala Lys Asn Lys Met Asn Tyr 2130 2135 2140 Lys Gln Lys Asp Leu Asp Asn Phe Thr Ser Lys Gly Lys His Leu Leu 2145 2150 2155 2160 Ser Glu Leu Lys Lys Ile His Ser Ser Asp Phe Ser Leu Val Lys Thr 2165 2170 2175 Asp Met Glu Ser Thr Val Asp Lys Trp Leu Asp Val Ser Glu Lys Leu 2180 2185 2190 Glu Glu Asn Met Asp Arg Leu Arg Val Ser Leu Ser Ile Trp Asp Asp 2195 2200 2205 Val Leu Ser Thr Arg Asp Glu Ile Glu Gly Trp Ser Asn Asn Cys Val 2210 2215 2220 Pro Gln Met Ala Glu Asn Ile Ser Asn Leu Asp Asn His Leu Arg Ala 2225 2230 2235 2240 Glu Glu Leu Leu Lys Glu Phe Glu Ser Glu Val Lys Asn Lys Ala Leu 2245 2250 2255 Arg Leu Glu Glu Leu His Ser Lys Val Asn Asp Leu Lys Glu Leu Thr 2260 2265 2270 Lys Asn Leu Glu Thr Pro Pro Asp Leu Gln Phe Ile Glu Ala Asp Leu 2275 2280 2285 Met Gln Lys Leu Glu His Ala Lys Glu Ile Thr Glu Val Ala Lys Gly 2290 2295 2300 Thr Leu Lys Asp Phe Thr Ala Gln Ser Thr Gln Val Glu Lys Phe Ile 2305 2310 2315 2320 Asn Asp Ile Thr Thr Trp Phe Thr Lys Val Glu Glu Ser Leu Met Asn 2325 2330 2335 Cys Ala Gln Asn Glu Thr Cys Glu Ala Leu Lys Lys Val Lys Asp Ile 2340 2345 2350 Gln Lys Glu Leu Gln Ser Gln Gln Ser Asn Ile Ser Ser Thr Gln Glu 2355 2360 2365 Asn Leu Asn Ser Leu Cys Arg Lys Tyr His Ser Ala Glu Leu Glu Ser 2370 2375 2380 Leu Gly Arg Ala Met Thr Gly Leu Ile Lys Lys His Glu Ala Val Ser 2385 2390 2395 2400 Gln Leu Cys Ser Lys Thr Gln Ala Ser Leu Gln Glu Ser Leu Glu Lys 2405 2410 2415 His Phe Ser Glu Ser Met Gln Glu Phe Gln Glu Trp Phe Leu Gly Ala 2420 2425 2430 Lys Ala Ala Ala Lys Glu Ser Ser Asp Arg Thr Gly Asp Ser Lys Val 2435 2440 2445 Leu Glu Ala Lys Leu His Asp Leu Gln Asn Ile Leu Asp Ser Val Ser 2450 2455 2460 Asp Gly Gln Ser Lys Leu Asp Ala Val Thr Gln Glu Gly Gln Thr Leu 2465 2470 2475 2480 Tyr Ala His Leu Ser Lys Gln Ile Val Ser Ser Ile Gln Glu Gln Ile 2485 2490 2495 Thr Lys Ala Asn Glu Glu Phe Gln Ala Phe Leu Lys Gln Cys Leu Lys 2500 2505 2510 Asp Lys Gln Ala Leu Gln Asp Cys Ala Ser Glu Leu Gly Ser Phe Glu 2515 2520 2525 Asp Gln His Arg Lys Leu Asn Leu Trp Ile His Glu Met Glu Glu Arg 2530 2535 2540 Phe Asn Thr Glu Asn Leu Gly Glu Ser Lys Gln His Ile Pro Glu Lys 2545 2550 2555 2560 Lys Asn Glu Val His Lys Val Glu Met Phe Leu Gly Glu Leu Leu Ala 2565 2570 2575 Ala Arg Glu Ser Leu Asp Lys Leu Ser Gln Arg Gly Gln Leu Leu Ser 2580 2585 2590 Glu Glu Gly His Gly Ala Gly Gln Glu Gly Arg Leu Cys Ser Gln Leu 2595 2600 2605 Leu Thr Ser His Gln Asn Leu Leu Arg Met Thr Lys Glu Lys Leu Arg 2610 2615 2620 Ser Cys Gln Val Ala Leu Gln Glu His Glu Ala Leu Glu Glu Ala Leu 2625 2630 2635 2640 Gln Ser Met Trp Phe Trp Val Lys Ala Ile Gln Asp Arg Leu Ala Cys 2645 2650 2655 Ala Glu Ser Thr Leu Gly Ser Lys Asp Thr Leu Glu Lys Arg Leu Ser 2660 2665 2670 Gln Ile Gln Asp Ile Leu Leu Met Lys Gly Glu Gly Glu Val Lys Leu 2675 2680 2685 Asn Met Ala Ile Gly Lys Gly Glu Gln Ala Leu Arg Ser Ser Asn Lys 2690 2695 2700 Glu Gly Gln Arg Val Ile Gln Thr Gln Leu Glu Thr Leu Lys Glu Val 2705 2710 2715 2720 Trp Ala Asp Ile Met Ser Ser Ser Val His Ala Gln Ser Thr Leu Glu 2725 2730 2735 Ser Val Ile Ser Gln Trp Asn Asp Tyr Val Glu Arg Lys Asn Gln Leu 2740 2745 2750 Glu Gln Trp Met Glu Ser Val Asp Gln Lys Ile Glu His Pro Leu Gln 2755 2760 2765 Pro Gln Pro Gly Leu Lys Glu Lys Phe Val Leu Leu Asp His Leu Gln 2770 2775 2780 Ser Ile Leu Ser Glu Ala Glu Asp His Thr Arg Ala Leu His Arg Leu 2785 2790 2795 2800 Ile Ala Lys Ser Arg Glu Leu Tyr Glu Lys Thr Glu Asp Glu Ser Phe 2805 2810 2815 Lys Asp Thr Ala Gln Glu Glu Leu Lys Thr Gln Phe Asn Asp Ile Met 2820 2825 2830 Thr Val Ala Lys Glu Lys Met Arg Lys Val Glu Glu Ile Val Lys Asp 2835 2840 2845 His Leu Met Tyr Leu Asp Ala Val His Glu Phe Thr Asp Trp Leu His 2850 2855 2860 Ser Ala Lys Glu Glu Leu His Arg Trp Ser Asp Met Ser Gly Asp Ser 2865 2870 2875 2880 Ser Ala Thr Gln Lys Lys Leu Ser Lys Ile Lys Glu Leu Ile Asp Ser 2885 2890 2895 Arg Glu Ile Gly Ala Ser Arg Leu Ser Arg Val Glu Ser Leu Ala Pro 2900 2905 2910 Glu Val Lys Gln Asn Thr Thr Ala Ser Gly Cys Glu Leu Met His Thr 2915 2920 2925 Glu Met Gln Ala Leu Arg Ala Asp Trp Lys Gln Trp Glu Asp Ser Val 2930 2935 2940 Phe Gln Thr Gln Ser Cys Leu Glu Asn Leu Val Ser Gln Met Ala Leu 2945 2950 2955 2960 Ser Glu Gln Glu Phe Ser Gly Gln Val Ala Gln Leu Glu Gln Ala Leu 2965 2970 2975 Glu Gln Phe Ser Ala Leu Leu Lys Thr Trp Ala Gln Gln Leu Thr Leu 2980 2985 2990 Leu Glu Gly Lys Asn Thr Asp Glu Glu Ile Val Glu Cys Trp His Lys 2995 3000 3005 Gly Gln Glu Ile Leu Asp Ala Leu Gln Lys Ala Glu Pro Arg Thr Glu 3010 3015 3020 Asp Leu Lys Ser Gln Leu Asn Glu Leu Cys Arg Phe Ser Arg Asp Leu 3025 3030 3035 3040 Ser Thr Tyr Ser Gly Lys Val Ser Gly Leu Ile Lys Glu Tyr Asn Cys 3045 3050 3055 Leu Cys Leu Gln Ala Ser Lys Gly Cys Gln Asn Lys Glu Gln Ile Leu 3060 3065 3070 Gln Gln Arg Phe Arg Lys Ala Phe Arg Asp Phe Gln Gln Trp Leu Val 3075 3080 3085 Asn Ala Lys Ile Thr Thr Ala Lys Cys Phe Asp Ile Pro Gln Asn Ile 3090 3095 3100 Ser Glu Val Ser Thr Ser Leu Gln Lys Ile Gln Glu Phe Leu Ser Glu 3105 3110 3115 3120 Ser Glu Asn Gly Gln His Lys Leu Asn Met Met Leu Ser Lys Gly Glu 3125 3130 3135 Leu Leu Ser Thr Leu Leu Thr Lys Glu Lys Ala Lys Gly Ile Gln Ala 3140 3145 3150 Lys Val Thr Ala Ala Lys Glu Asp Trp Lys Asn Phe His Ser Asn Leu 3155 3160 3165 His Gln Lys Glu Ser Ala Leu Glu Asn Leu Lys Ile Gln Met Lys Asp 3170 3175 3180 Phe Glu Val Ser Ala Glu Pro Ile Gln Asp Trp Leu Ser Lys Thr Glu 3185 3190 3195 3200 Lys Met Val His Glu Ser Ser Asn Arg Leu Tyr Asp Leu Pro Ala Lys 3205 3210 3215 Arg Arg Glu Gln Gln Lys Leu Gln Ser Val Leu Glu Glu Ile His Cys 3220 3225 3230 Tyr Glu Pro Gln Leu Asn Arg Leu Lys Glu Lys Ala Gln Gln Leu Trp 3235 3240 3245 Glu Gly Gln Ala Ala Ser Lys Ser Phe Arg His Arg Val Ser Gln Leu 3250 3255 3260 Ser Ser Gln Tyr Leu Ala Leu Ser Asn Leu Thr Lys Glu Lys Val Ser 3265 3270 3275 3280 Arg Leu Asp Arg Ile Val Ala Glu His Asn Gln Phe Ser Leu Gly Ile 3285 3290 3295 Lys Glu Leu Gln Asp Trp Met Thr Asp Ala Ile His Met Leu Asp Ser 3300 3305 3310 Tyr Cys His Pro Thr Ser Asp Lys Ser Val Leu Asp Ser Arg Thr Leu 3315 3320 3325 Lys Leu Glu Ala Leu Leu Ser Val Lys Gln Glu Lys Glu Ile Gln Met 3330 3335 3340 Lys Met Ile Val Thr Arg Gly Glu Ser Val Leu Gln Asn Thr Ser Pro 3345 3350 3355 3360 Glu Gly Ile Pro Thr Ile Gln Gln Gln Leu Gln Ser Val Lys Asp Met 3365 3370 3375 Trp Ala Ser Leu Leu Ser Ala Gly Ile Arg Cys Lys Ser Gln Leu Glu 3380 3385 3390 Gly Ala Leu Ser Lys Trp Thr Ser Tyr Gln Asp Gly Val Arg Gln Phe 3395 3400 3405 Ser Gly Trp Met Asp Ser Met Glu Ala Asn Leu Asn Glu Ser Glu Arg 3410 3415 3420 Gln His Ala Glu Leu Arg Asp Lys Thr Thr Met Leu Gly Lys Ala Lys 3425 3430 3435 3440 Leu Leu Asn Glu Glu Val Leu Ser Tyr Ser Ser Leu Leu Glu Thr Ile 3445 3450 3455 Glu Val Lys Gly Ala Gly Met Thr Glu His Tyr Val Thr Gln Leu Glu 3460 3465 3470 Leu Gln Asp Leu Gln Glu Arg Tyr Arg Ala Ile Gln Glu Arg Ala Lys 3475 3480 3485 Glu Ala Val Thr Lys Ser Glu Lys Leu Val Arg Leu His Gln Glu Tyr 3490 3495 3500 Gln Arg Asp Leu Lys Ala Phe Glu Val Trp Leu Gly Gln Glu Gln Glu 3505 3510 3515 3520 Lys Leu Asp Gln Tyr Ser Val Leu Glu Gly Asp Ala His Thr His Glu 3525 3530 3535 Thr Thr Leu Arg Asp Leu Gln Glu Leu Gln Val His Cys Ala Glu Gly 3540 3545 3550 Gln Ala Leu Leu Asn Ser Val Leu His Thr Arg Glu Asp Val Ile Pro 3555 3560 3565 Ser Gly Ile Pro Gln Ala Glu Asp Arg Ala Leu Glu Ser Leu Arg Gln 3570 3575 3580 Asp Trp Gln Ala Tyr Gln His Arg Leu Ser Glu Thr Arg Thr Gln Phe 3585 3590 3595 3600 Asn Asn Val Val Asn Lys Leu Arg Leu Met Glu Gln Lys Phe Gln Gln 3605 3610 3615 Val Asp Glu Trp Leu Lys Thr Ala Glu Glu Lys Lys Trp His Glu Glu 3620 3625 3630 Val Thr Ala Tyr Arg Asp Glu Val Glu Glu Val Gly Ala Arg Ala Gln 3635 3640 3645 Glu Ile Leu Asp Glu Ser His Val Asn Ser Arg Met Gly Cys Gln Ala 3650 3655 3660 Thr Gln Leu Thr Ser Arg Tyr Gln Ala Leu Leu Leu Gln Val Leu Glu 3665 3670 3675 3680 Gln Ile Lys Phe Leu Glu Glu Glu Ile Gln Ser Leu Glu Glu Ser Glu 3685 3690 3695 Ser Ser Leu Ser Ser Tyr Ser Asp Trp Tyr Gly Ser Thr His Lys Asn 3700 3705 3710 Phe Lys Asn Val Ala Thr Lys Ile Asp Lys Val Asp Thr Val Met Met 3715 3720 3725 Gly Lys Lys Leu Lys Thr Leu Glu Val Leu Leu Lys Asp Met Glu Lys 3730 3735 3740 Gly His Ser Leu Leu Lys Ser Ala Arg Glu Lys Gly Glu Arg Ala Val 3745 3750 3755 3760 Lys Tyr Leu Glu Glu Gly Glu Ala Glu Arg Leu Arg Lys Glu Ile His 3765 3770 3775 Asp His Met Glu Gln Leu Lys Glu Leu Thr Ser Thr Val Arg Lys Glu 3780 3785 3790 His Met Thr Leu Glu Lys Gly Leu His Leu Ala Lys Glu Phe Ser Asp 3795 3800 3805 Lys Cys Lys Ala Leu Thr Gln Trp Ile Ala Glu Tyr Gln Glu Ile Leu 3810 3815 3820 His Val Pro Glu Glu Pro Lys Met Glu Leu Tyr Glu Lys Lys Ala Gln 3825 3830 3835 3840 Leu Ser Lys Tyr Lys Ser Leu Gln Gln Thr Val Leu Ser His Glu Pro 3845 3850 3855 Ser Val Lys Ser Val Arg Glu Lys Gly Glu Ala Leu Leu Glu Leu Val 3860 3865 3870 Gln Asp Val Thr Leu Lys Asp Lys Ile Asp Gln Leu Gln Ser Asp Tyr 3875 3880 3885 Gln Asp Leu Cys Ser Ile Gly Lys Ala Met Met Glu Glu Ile Ala Gly 3890 3895 3900 Phe Glu Asp Arg Leu Asn Asn Leu Gln Met Lys Gly Asp Thr Leu Ile 3905 3910 3915 3920 Gly Gln Cys Ala Asp His Leu Gln Ala Lys Leu Lys Gln Asn Val His 3925 3930 3935 Ala His Leu Gln Gly Thr Lys Asp Ser Tyr Ser Ala Ile Cys Ser Thr 3940 3945 3950 Ala Gln Arg Met Tyr Gln Ser Leu Glu His Glu Leu Gln Lys His Val 3955 3960 3965 Ser Arg Gln Asp Thr Leu Gln Gln Cys Gln Ala Trp Leu Ser Ala Val 3970 3975 3980 Gln Pro Asp Leu Glu Pro Ser Pro Gln Pro Pro Leu Ser Arg Ala Glu 3985 3990 3995 4000 Ala Ile Lys Gln Val Lys His Phe Arg Ala Leu Gln Glu Gln Ala Arg 4005 4010 4015 Thr Tyr Leu Asp Leu Leu Cys Ser Met Cys Asp Leu Ser Asn Ala Ser 4020 4025 4030 Val Lys Thr Thr Ala Lys Asp Ile Gln Gln Thr Glu Gln Thr Ile Glu 4035 4040 4045 Gln Lys Leu Val Gln Ala Gln Asn Leu Thr Gln Gly Trp Glu Glu Ile 4050 4055 4060 Lys His Leu Lys Ser Glu Leu Trp Ile Tyr Leu Gln Asp Ala Asp Gln 4065 4070 4075 4080 Gln Leu Gln Asn Met Lys Arg Arg His Ser Glu Leu Glu Leu Asn Ile 4085 4090 4095 Ala Gln Asn Met Val Ser Gln Val Lys Asp Phe Val Lys Lys Leu Gln 4100 4105 4110 Ser Lys Gln Ala Ser Val Asn Thr Ile Ile Glu Lys Val Asn Lys Leu 4115 4120 4125 Thr Lys Lys Glu Glu Ser Pro Glu His Lys Glu Ile Asn His Leu Asn 4130 4135 4140 Asp Gln Trp Leu Asp Leu Cys Arg Gln Ser Asn Asn Leu Cys Leu Gln 4145 4150 4155 4160 Arg Glu Glu Asp Leu Gln Arg Thr Arg Asp Tyr His Asp Cys Met Asn 4165 4170 4175 Val Val Glu Val Phe Leu Glu Lys Phe Thr Thr Glu Trp Asp Asn Leu 4180 4185 4190 Ala Arg Ser Asp Ala Glu Ser Thr Ala Val His Leu Glu Ala Leu Lys 4195 4200 4205 Lys Leu Ala Leu Ala Leu Gln Glu Arg Lys Tyr Ala Ile Glu Asp Leu 4210 4215 4220 Lys Asp Gln Lys Gln Lys Met Ile Glu His Leu Asn Leu Asp Asp Lys 4225 4230 4235 4240 Glu Leu Val Lys Glu Gln Thr Ser His Leu Glu Gln Arg Trp Phe Gln 4245 4250 4255 Leu Glu Asp Leu Ile Lys Arg Lys Ile Gln Val Ser Val Thr Asn Leu 4260 4265 4270 Glu Glu Leu Asn Val Val Gln Ser Arg Phe Gln Glu Leu Met Glu Trp 4275 4280 4285 Ala Glu Glu Gln Gln Pro Asn Ile Ala Glu Ala Leu Lys Gln Ser Pro 4290 4295 4300 Pro Pro Asp Met Ala Gln Asn Leu Leu Met Asp His Leu Ala Ile Cys 4305 4310 4315 4320 Ser Glu Leu Glu Ala Lys Gln Met Leu Leu Lys Ser Leu Ile Lys Asp 4325 4330 4335 Ala Asp Arg Val Met Ala Asp Leu Gly Leu Asn Glu Arg Gln Val Ile 4340 4345 4350 Gln Lys Ala Leu Ser Asp Ala Gln Ser His Val Asn Cys Leu Ser Asp 4355 4360 4365 Leu Val Gly Gln Arg Arg Lys Tyr Leu Asn Lys Ala Leu Ser Glu Lys 4370 4375 4380 Thr Gln Phe Leu Met Ala Val Phe Gln Ala Thr Ser Gln Ile Gln Gln 4385 4390 4395 4400 His Glu Arg Lys Ile Met Phe Arg Glu His Ile Cys Leu Leu Pro Asp 4405 4410 4415 Asp Val Ser Lys Gln Val Lys Thr Cys Lys Ser Ala Gln Ala Ser Leu 4420 4425 4430 Lys Thr Tyr Gln Asn Glu Val Thr Gly Leu Trp Ala Gln Gly Arg Glu 4435 4440 4445 Leu Met Lys Glu Val Thr Glu Gln Glu Lys Ser Glu Val Leu Gly Lys 4450 4455 4460 Leu Gln Glu Leu Gln Ser Val Tyr Asp Ser Val Leu Gln Lys Cys Ser 4465 4470 4475 4480 His Arg Leu Gln Glu Leu Glu Lys Asn Leu Val Ser Arg Lys His Phe 4485 4490 4495 Lys Glu Asp Phe Asp Lys Ala Cys His Trp Leu Lys Gln Ala Asp Ile 4500 4505 4510 Val Thr Phe Pro Glu Ile Asn Leu Met Asn Glu Ser Ser Glu Leu His 4515 4520 4525 Thr Gln Leu Ala Lys Tyr Gln Asn Ile Leu Glu Gln Ser Pro Glu Tyr 4530 4535 4540 Glu Asn Leu Leu Leu Thr Leu Gln Arg Thr Gly Gln Thr Ile Leu Pro 4545 4550 4555 4560 Ser Leu Asn Glu Val Asp His Ser Tyr Leu Ser Glu Lys Leu Asn Ala 4565 4570 4575 Leu Pro Arg Gln Phe Asn Val Ile Val Ala Leu Ala Lys Asp Lys Phe 4580 4585 4590 Tyr Lys Val Gln Glu Ala Ile Leu Ala Arg Lys Glu Tyr Ala Ser Leu 4595 4600 4605 Ile Glu Leu Thr Thr Gln Ser Leu Ser Glu Leu Glu Ala Gln Phe Leu 4610 4615 4620 Arg Met Ser Lys Val Pro Thr Asp Leu Ala Val Glu Glu Ala Leu Ser 4625 4630 4635 4640 Leu Gln Asp Gly Cys Arg Ala Ile Leu Asp Glu Val Ala Gly Leu Gly 4645 4650 4655 Glu Ala Val Asp Glu Leu Asn Gln Lys Lys Glu Gly Phe Arg Ser Thr 4660 4665 4670 Gly Gln Pro Trp Gln Pro Asp Lys Met Leu His Leu Val Thr Leu Tyr 4675 4680 4685 His Arg Leu Lys Arg Gln Thr Glu Gln Arg Val Ser Leu Leu Glu Asp 4690 4695 4700 Thr Thr Ser Ala Tyr Gln Glu His Glu Lys Met Cys Gln Gln Leu Glu 4705 4710 4715 4720 Arg Gln Leu Lys Ser Val Lys Glu Glu Gln Ser Lys Val Asn Glu Glu 4725 4730 4735 Thr Leu Pro Ala Glu Glu Lys Leu Lys Met Tyr His Ser Leu Ala Gly 4740 4745 4750 Ser Leu Gln Asp Ser Gly Ile Val Leu Lys Arg Val Thr Ile His Leu 4755 4760 4765 Glu Asp Leu Ala Pro His Leu Asp Pro Leu Ala Tyr Glu Lys Ala Arg 4770 4775 4780 His Gln Ile Gln Ser Trp Gln Gly Glu Leu Lys Leu Leu Thr Ser Ala 4785 4790 4795 4800 Ile Gly Glu Thr Val Thr Glu Cys Glu Ser Arg Met Val Gln Ser Ile 4805 4810 4815 Asp Phe Gln Thr Glu Met Ser Arg Ser Leu Asp Trp Leu Arg Arg Val 4820 4825 4830 Lys Ala Glu Leu Ser Gly Pro Val Tyr Leu Asp Leu Asn Leu Gln Asp 4835 4840 4845 Ile Gln Glu Glu Ile Arg Lys Ile Gln Ile His Gln Glu Glu Val Gln 4850 4855 4860 Ser Ser Leu Arg Ile Met Asn Ala Leu Ser His Lys Glu Lys Glu Lys 4865 4870 4875 4880 Phe Thr Lys Ala Lys Glu Leu Ile Ser Ala Asp Leu Glu His Ser Leu 4885 4890 4895 Ala Glu Leu Ser Glu Leu Asp Gly Asp Ile Gln Glu Ala Leu Arg Thr 4900 4905 4910 Arg Gln Ala Thr Leu Thr Glu Ile Tyr Ser Gln Cys Gln Arg Tyr Tyr 4915 4920 4925 Gln Val Phe Gln Ala Ala Asn Asp Trp Leu Glu Asp Ala Gln Glu Leu 4930 4935 4940 Leu Gln Leu Ala Gly Asn Gly Leu Asp Val Glu Ser Ala Glu Glu Asn 4945 4950 4955 4960 Leu Lys Ser His Met Glu Phe Phe Ser Thr Glu Asp Gln Phe His Ser 4965 4970 4975 Asn Leu Glu Glu Leu His Ser Leu Val Ala Thr Leu Asp Pro Leu Ile 4980 4985 4990 Lys Pro Thr Gly Lys Glu Asp Leu Glu Gln Lys Val Ala Ser Leu Glu 4995 5000 5005 Leu Arg Ser Gln Arg Met Ser Arg Asp Ser Gly Ala Gln Val Asp Leu 5010 5015 5020 Leu Gln Arg Cys Thr Ala Gln Trp His Asp Tyr Gln Lys Ala Arg Glu 5025 5030 5035 5040 Glu Val Ile Glu Leu Met Asn Asp Thr Glu Lys Lys Leu Ser Glu Phe 5045 5050 5055 Ser Leu Leu Lys Thr Ser Ser Ser His Glu Ala Glu Glu Lys Leu Ser 5060 5065 5070 Glu His Lys Ala Leu Val Ser Val Val Asn Ser Phe His Glu Lys Ile 5075 5080 5085 Val Ala Leu Glu Glu Lys Ala Ser Gln Leu Glu Lys Thr Gly Asn Asp 5090 5095 5100 Ala Ser Lys Ala Thr Leu Ser Arg Ser Met Thr Thr Val Trp Gln Arg 5105 5110 5115 5120 Trp Thr Arg Leu Arg Ala Val Ala Gln Asp Gln Glu Lys Ile Leu Glu 5125 5130 5135 Asp Ala Val Asp Glu Trp Thr Gly Phe Asn Asn Lys Val Lys Lys Ala 5140 5145 5150 Thr Glu Met Ile Asp Gln Leu Gln Asp Lys Leu Pro Gly Ser Ser Ala 5155 5160 5165 Glu Lys Ala Ser Lys Ala Glu Leu Leu Thr Leu Leu Glu Tyr His Asp 5170 5175 5180 Thr Phe Val Leu Glu Leu Glu Gln Gln Gln Ser Ala Leu Gly Met Leu 5185 5190 5195 5200 Arg Gln Gln Thr Leu Ser Met Leu Gln Asp Gly Ala Ala Pro Thr Pro 5205 5210 5215 Gly Glu Glu Pro Pro Leu Met Gln Glu Ile Thr Ala Met Gln Asp Arg 5220 5225 5230 Cys Leu Asn Met Gln Glu Lys Val Lys Thr Asn Gly Lys Leu Val Lys 5235 5240 5245 Gln Glu Leu Lys Asp Arg Glu Met Val Glu Thr Gln Ile Asn Ser Val 5250 5255 5260 Lys Cys Trp Val Gln Glu Thr Lys Glu Tyr Leu Gly Asn Pro Thr Ile 5265 5270 5275 5280 Glu Ile Asp Ala Gln Leu Glu Glu Leu Gln Ile Leu Leu Thr Glu Ala 5285 5290 5295 Thr Asn His Arg Gln Asn Ile Glu Lys Met Ala Glu Glu Gln Lys Glu 5300 5305 5310 Lys Tyr Leu Gly Leu Tyr Thr Ile Leu Pro Ser Glu Leu Ser Leu Gln 5315 5320 5325 Leu Ala Glu Val Ala Leu Asp Leu Lys Ile Arg Asp Gln Ile Gln Asp 5330 5335 5340 Lys Ile Lys Glu Val Glu Gln Ser Lys Ala Thr Ser Gln Glu Leu Ser 5345 5350 5355 5360 Arg Gln Ile Gln Lys Leu Ala Lys Asp Leu Thr Thr Ile Leu Thr Lys 5365 5370 5375 Leu Lys Ala Lys Thr Asp Asn Val Val Gln Ala Lys Thr Asp Gln Lys 5380 5385 5390 Val Leu Gly Glu Glu Leu Asp Gly Cys Asn Ser Lys Leu Met Glu Leu 5395 5400 5405 Asp Ala Ala Val Gln Lys Phe Leu Glu Gln Asn Gly Gln Leu Gly Lys 5410 5415 5420 Pro Leu Ala Lys Lys Ile Gly Lys Leu Thr Glu Leu His Gln Gln Thr 5425 5430 5435 5440 Ile Arg Gln Ala Glu Asn Arg Leu Ser Lys Leu Asn Gln Ala Ala Ser 5445 5450 5455 His Leu Glu Glu Tyr Asn Glu Met Leu Glu Leu Ile Leu Lys Trp Ile 5460 5465 5470 Glu Lys Ala Lys Val Leu Ala His Gly Thr Ile Ala Trp Asn Ser Ala 5475 5480 5485 Ser Gln Leu Arg Glu Gln Tyr Ile Leu His Gln Thr Leu Leu Glu Glu 5490 5495 5500 Ser Lys Glu Ile Asp Ser Glu Leu Glu Ala Met Thr Glu Lys Leu Gln 5505 5510 5515 5520 Tyr Leu Thr Ser Val Tyr Cys Thr Glu Lys Met Ser Gln Gln Val Ala 5525 5530 5535 Glu Leu Gly Arg Glu Thr Glu Glu Leu Arg Gln Met Ile Lys Ile Arg 5540 5545 5550 Leu Gln Asn Leu Gln Asp Ala Ala Lys Asp Met Lys Lys Phe Glu Ala 5555 5560 5565 Glu Leu Lys Lys Leu Gln Ala Ala Leu Glu Gln Ala Gln Ala Thr Leu 5570 5575 5580 Thr Ser Pro Glu Val Gly Arg Leu Ser Leu Lys Glu Gln Leu Ser His 5585 5590 5595 5600 Arg Gln His Leu Leu Ser Glu Met Glu Ser Leu Lys Pro Lys Val Gln 5605 5610 5615 Ala Val Gln Leu Cys Gln Ser Ala Leu Arg Ile Pro Glu Asp Val Val 5620 5625 5630 Ala Ser Leu Pro Leu Cys His Ala Ala Leu Arg Leu Gln Glu Glu Ala 5635 5640 5645 Ser Arg Leu Gln His Thr Ala Ile Gln Gln Cys Asn Ile Met Gln Ala 5650 5655 5660 Ala Val Val Gln Tyr Glu Gln Tyr Glu Gln Glu Met Lys His Leu Gln 5665 5670 5675 5680 Gln Leu Ile Glu Gly Ala His Arg Glu Ile Glu Asp Lys Pro Val Ala 5685 5690 5695 Thr Ser Asn Ile Gln Glu Leu Gln Ala Gln Ile Ser Arg His Glu Glu 5700 5705 5710 Leu Ala Gln Lys Ile Lys Gly Tyr Gln Glu Gln Ile Ala Ser Leu Asn 5715 5720 5725 Ser Lys Cys Lys Met Leu Thr Met Lys Ala Lys His Ala Thr Met Leu 5730 5735 5740 Leu Thr Val Thr Glu Val Glu Gly Leu Ala Glu Gly Thr Glu Asp Leu 5745 5750 5755 5760 Asp Gly Glu Leu Leu Pro Thr Pro Ser Ala His Pro Ser Val Val Met 5765 5770 5775 Met Thr Ala Gly Arg Cys His Thr Leu Leu Ser Pro Val Thr Glu Glu 5780 5785 5790 Ser Gly Glu Glu Gly Thr Asn Ser Glu Ile Ser Ser Pro Pro Ala Cys 5795 5800 5805 Arg Ser Pro Ser Pro Val Ala Asn Thr Asp Ala Ser Val Asn Gln Asp 5810 5815 5820 Ile Ala Tyr Tyr Gln Ala Leu Ser Ala Glu Arg Leu Gln Thr Asp Ala 5825 5830 5835 5840 Ala Lys Ile His Pro Ser Thr Ser Ala Ser Gln Glu Phe Tyr Glu Pro 5845 5850 5855 Gly Leu Glu Pro Ser Ala Thr Ala Lys Leu Gly Asp Leu Gln Arg Ser 5860 5865 5870 Trp Glu Thr Leu Lys Asn Val Ile Ser Glu Lys Gln Arg Thr Leu Tyr 5875 5880 5885 Glu Ala Leu Glu Arg Gln Gln Lys Tyr Gln Asp Ser Leu Gln Ser Ile 5890 5895 5900 Ser Thr Lys Met Glu Ala Ile Glu Leu Lys Leu Ser Glu Ser Pro Glu 5905 5910 5915 5920 Pro Gly Arg Ser Pro Glu Ser Gln Met Ala Glu His Gln Ala Leu Met 5925 5930 5935 Asp Glu Ile Leu Met Leu Gln Asp Glu Ile Asn Glu Leu Gln Ser Ser 5940 5945 5950 Leu Ala Glu Glu Leu Val Ser Glu Ser Cys Glu Ala Asp Pro Ala Glu 5955 5960 5965 Gln Leu Ala Leu Gln Ser Thr Leu Thr Val Leu Ala Glu Arg Met Ser 5970 5975 5980 Thr Ile Arg Met Lys Ala Ser Gly Lys Arg Gln Leu Leu Glu Glu Lys 5985 5990 5995 6000 Leu Asn Asp Gln Leu Glu Glu Gln Arg Gln Glu Gln Ala Leu Gln Arg 6005 6010 6015 Tyr Arg Cys Glu Ala Asp Glu Leu Asp Ser Trp Leu Leu Ser Thr Lys 6020 6025 6030 Ala Thr Leu Asp Thr Ala Leu Ser Pro Pro Lys Glu Pro Met Asp Met 6035 6040 6045 Glu Ala Gln Leu Met Asp Cys Gln Asn Met Leu Val Glu Ile Glu Gln 6050 6055 6060 Lys Val Val Ala Leu Ser Glu Leu Ser Val His Asn Glu Asn Leu Leu 6065 6070 6075 6080 Leu Glu Gly Lys Ala His Thr Lys Asp Glu Ala Glu Gln Leu Ala Gly 6085 6090 6095 Lys Leu Arg Arg Leu Lys Gly Ser Leu Leu Glu Leu Gln Arg Ala Leu 6100 6105 6110 His Asp Lys Gln Leu Asn Met Gln Gly Thr Ala Gln Glu Lys Glu Glu 6115 6120 6125 Ser Asp Val Asp Leu Thr Ala Thr Gln Ser Pro Gly Val Gln Glu Trp 6130 6135 6140 Leu Ala Gln Ala Arg Thr Thr Trp Thr Gln Gln Arg Gln Ser Ser Leu 6145 6150 6155 6160 Gln Gln Gln Lys Glu Leu Glu Gln Glu Leu Ala Glu Gln Lys Ser Leu 6165 6170 6175 Leu Arg Ser Val Ala Ser Arg Gly Glu Glu Ile Leu Ile Gln His Ser 6180 6185 6190 Ala Ala Glu Thr Ser Gly Asp Ala Gly Glu Lys Pro Asp Val Leu Ser 6195 6200 6205 Gln Glu Leu Gly Met Glu Gly Glu Lys Ser Ser Ala Glu Asp Gln Met 6210 6215 6220 Arg Met Lys Trp Glu Ser Leu His Gln Glu Phe Ser Thr Lys Gln Lys 6225 6230 6235 6240 Leu Leu Gln Asn Val Leu Glu Gln Glu Gln Glu Gln Val Leu Tyr Ser 6245 6250 6255 Arg Pro Asn Arg Leu Leu Ser Gly Val Pro Leu Tyr Lys Gly Asp Val 6260 6265 6270 Pro Thr Gln Asp Lys Ser Ala Val Thr Ser Leu Leu Asp Gly Leu Asn 6275 6280 6285 Gln Ala Phe Glu Glu Val Ser Ser Gln Ser Gly Gly Ala Lys Arg Gln 6290 6295 6300 Ser Ile His Leu Glu Gln Lys Leu Tyr Asp Gly Val Ser Ala Thr Ser 6305 6310 6315 6320 Thr Trp Leu Asp Asp Val Glu Glu Arg Leu Phe Val Ala Thr Ala Leu 6325 6330 6335 Leu Pro Glu Glu Thr Glu Thr Cys Leu Phe Asn Gln Glu Ile Leu Ala 6340 6345 6350 Lys Asp Ile Lys Glu Met Ser Glu Glu Met Asp Lys Asn Lys Asn Leu 6355 6360 6365 Phe Ser Gln Ala Phe Pro Glu Asn Gly Asp Asn Arg Asp Val Ile Glu 6370 6375 6380 Asp Thr Leu Gly Cys Leu Leu Gly Arg Leu Ser Leu Leu Asp Ser Val 6385 6390 6395 6400 Val Asn Gln Arg Cys His Gln Met Lys Glu Arg Leu Gln Gln Ile Leu 6405 6410 6415 Asn Phe Gln Asn Asp Leu Lys Val Leu Phe Thr Ser Leu Ala Asp Asn 6420 6425 6430 Lys Tyr Ile Ile Leu Gln Lys Leu Ala Asn Val Phe Glu Gln Pro Val 6435 6440 6445 Ala Glu Gln Ile Glu Ala Ile Gln Gln Ala Glu Asp Gly Leu Lys Glu 6450 6455 6460 Phe Asp Ala Gly Ile Ile Glu Leu Lys Arg Arg Gly Asp Lys Leu Gln 6465 6470 6475 6480 Val Glu Gln Pro Ser Met Gln Glu Leu Ser Lys Leu Gln Asp Met Tyr 6485 6490 6495 Asp Glu Leu Met Met Ile Ile Gly Ser Arg Arg Ser Gly Leu Asn Gln 6500 6505 6510 Asn Leu Thr Leu Lys Ser Gln Tyr Glu Arg Ala Leu Gln Asp Leu Ala 6515 6520 6525 Asp Leu Leu Glu Thr Gly Gln Glu Lys Met Ala Gly Asp Gln Lys Ile 6530 6535 6540 Ile Val Ser Ser Lys Glu Glu Ile Gln Gln Leu Leu Asp Lys His Lys 6545 6550 6555 6560 Glu Tyr Phe Gln Gly Leu Glu Ser His Met Ile Leu Thr Glu Thr Leu 6565 6570 6575 Phe Arg Lys Ile Ile Ser Phe Ala Val Gln Lys Glu Thr Gln Phe His 6580 6585 6590 Thr Glu Leu Met Ala Gln Ala Ser Ala Val Leu Lys Arg Ala His Lys 6595 6600 6605 Arg Gly Val Glu Leu Glu Tyr Ile Leu Glu Thr Trp Ser His Leu Asp 6610 6615 6620 Glu Asp Gln Gln Glu Leu Ser Arg Gln Leu Glu Val Val Glu Ser Ser 6625 6630 6635 6640 Ile Pro Ser Val Gly Leu Val Glu Glu Asn Glu Asp Arg Leu Ile Asp 6645 6650 6655 Arg Ile Thr Leu Tyr Gln His Leu Lys Ser Ser Leu Asn Glu Tyr Gln 6660 6665 6670 Pro Lys Leu Tyr Gln Val Leu Asp Asp Gly Lys Arg Leu Leu Ile Ser 6675 6680 6685 Ile Ser Cys Ser Asp Leu Glu Ser Gln Leu Asn Gln Leu Gly Glu Cys 6690 6695 6700 Trp Leu Ser Asn Thr Asn Lys Met Ser Lys Glu Leu His Arg Leu Glu 6705 6710 6715 6720 Thr Ile Leu Lys His Trp Thr Arg Tyr Gln Ser Glu Ser Ala Asp Leu 6725 6730 6735 Ile His Trp Leu Gln Ser Ala Lys Asp Arg Leu Glu Phe Trp Thr Gln 6740 6745 6750 Gln Ser Val Thr Val Pro Gln Glu Leu Glu Met Val Arg Asp His Leu 6755 6760 6765 Asn Ala Phe Leu Glu Phe Ser Lys Glu Val Asp Ala Gln Ser Ser Leu 6770 6775 6780 Lys Ser Ser Val Leu Ser Thr Gly Asn Gln Leu Leu Arg Leu Lys Lys 6785 6790 6795 6800 Val Asp Thr Ala Thr Leu Arg Ser Glu Leu Ser Arg Ile Asp Ser Gln 6805 6810 6815 Trp Thr Asp Leu Leu Thr Asn Ile Pro Ala Val Gln Glu Lys Leu His 6820 6825 6830 Gln Leu Gln Met Asp Lys Leu Pro Ser Arg His Ala Ile Ser Glu Val 6835 6840 6845 Met Ser Trp Ile Ser Leu Met Glu Asn Val Ile Gln Lys Asp Glu Asp 6850 6855 6860 Asn Ile Lys Asn Ser Ile Gly Tyr Lys Ala Ile His Glu Tyr Leu Gln 6865 6870 6875 6880 Lys Tyr Lys Gly Phe Lys Ile Asp Ile Asn Cys Lys Gln Leu Thr Val 6885 6890 6895 Asp Phe Val Asn Gln Ser Val Leu Gln Ile Ser Ser Gln Asp Val Glu 6900 6905 6910 Ser Lys Arg Ser Asp Lys Thr Asp Phe Ala Glu Gln Leu Gly Ala Met 6915 6920 6925 Asn Lys Ser Trp Gln Ile Leu Gln Gly Leu Val Thr Glu Lys Ile Gln 6930 6935 6940 Leu Leu Glu Gly Leu Leu Glu Ser Trp Ser Glu Tyr Glu Asn Asn Val 6945 6950 6955 6960 Gln Cys Leu Lys Thr Trp Phe Glu Thr Gln Glu Lys Arg Leu Lys Gln 6965 6970 6975 Gln His Arg Ile Gly Asp Gln Ala Ser Val Gln Asn Ala Leu Lys Asp 6980 6985 6990 Cys Gln Asp Leu Glu Asp Leu Ile Lys Ala Lys Glu Lys Glu Val Glu 6995 7000 7005 Lys Ile Glu Gln Asn Gly Leu Ala Leu Ile Gln Asn Lys Lys Glu Asp 7010 7015 7020 Val Ser Ser Ile Val Met Ser Thr Leu Arg Glu Leu Gly Gln Thr Trp 7025 7030 7035 7040 Ala Asn Leu Asp His Met Val Gly Gln Leu Lys Ile Leu Leu Lys Ser 7045 7050 7055 Val Leu Asp Gln Trp Ser Ser His Lys Val Ala Phe Asp Lys Ile Asn 7060 7065 7070 Ser Tyr Leu Met Glu Ala Arg Tyr Ser Leu Ser Arg Phe Arg Leu Leu 7075 7080 7085 Thr Gly Ser Leu Glu Ala Val Gln Val Gln Val Asp Asn Leu Gln Asn 7090 7095 7100 Leu Gln Asp Asp Leu Glu Lys Gln Glu Arg Ser Leu Gln Lys Phe Gly 7105 7110 7115 7120 Ser Ile Thr Asn Gln Leu Leu Lys Glu Cys His Pro Pro Val Thr Glu 7125 7130 7135 Thr Leu Thr Asn Thr Leu Lys Glu Val Asn Met Arg Trp Asn Asn Leu 7140 7145 7150 Leu Glu Glu Ile Ala Glu Gln Leu Gln Ser Ser Lys Ala Leu Leu Gln 7155 7160 7165 Leu Trp Gln Arg Tyr Lys Asp Tyr Ser Lys Gln Cys Ala Ser Thr Val 7170 7175 7180 Gln Gln Gln Glu Asp Arg Thr Asn Glu Leu Leu Lys Ala Ala Thr Asn 7185 7190 7195 7200 Lys Asp Ile Ala Asp Asp Glu Val Ala Thr Trp Ile Gln Asp Cys Asn 7205 7210 7215 Asp Leu Leu Lys Gly Leu Gly Thr Val Lys Asp Ser Leu Phe Phe Leu 7220 7225 7230 His Glu Leu Gly Glu Gln Leu Lys Gln Gln Val Asp Ala Ser Ala Ala 7235 7240 7245 Ser Ala Ile Gln Ser Asp Gln Leu Ser Leu Ser Gln His Leu Cys Ala 7250 7255 7260 Leu Glu Gln Ala Leu Cys Lys Gln Gln Thr Ser Leu Gln Ala Gly Val 7265 7270 7275 7280 Leu Asp Tyr Glu Thr Phe Ala Lys Ser Leu Glu Ala Leu Glu Ala Trp 7285 7290 7295 Ile Val Glu Ala Glu Glu Ile Leu Gln Gly Gln Asp Pro Ser His Ser 7300 7305 7310 Ser Asp Leu Ser Thr Ile Gln Glu Arg Met Glu Glu Leu Lys Gly Gln 7315 7320 7325 Met Leu Lys Phe Ser Ser Met Ala Pro Asp Leu Asp Arg Leu Asn Glu 7330 7335 7340 Leu Gly Tyr Arg Leu Pro Leu Asn Asp Lys Glu Ile Lys Arg Met Gln 7345 7350 7355 7360 Asn Leu Asn Arg His Trp Ser Leu Ile Ser Ser Gln Thr Thr Glu Arg 7365 7370 7375 Phe Ser Lys Leu Gln Ser Phe Leu Leu Gln His Gln Thr Phe Leu Glu 7380 7385 7390 Lys Cys Glu Thr Trp Met Glu Phe Leu Val Gln Thr Glu Gln Lys Leu 7395 7400 7405 Ala Val Glu Ile Ser Gly Asn Tyr Gln His Leu Leu Glu Gln Gln Arg 7410 7415 7420 Ala His Glu Leu Phe Gln Ala Glu Met Phe Ser Arg Gln Gln Ile Leu 7425 7430 7435 7440 His Ser Ile Ile Ile Asp Gly Gln Arg Leu Leu Glu Gln Gly Gln Val 7445 7450 7455 Asp Asp Arg Asp Glu Phe Asn Leu Lys Leu Thr Leu Leu Ser Asn Gln 7460 7465 7470 Trp Gln Gly Val Ile Arg Arg Ala Gln Gln Arg Arg Gly Ile Ile Asp 7475 7480 7485 Ser Gln Ile Arg Gln Trp Gln Arg Tyr Arg Glu Met Ala Glu Lys Leu 7490 7495 7500 Arg Lys Trp Leu Val Glu Val Ser Tyr Leu Pro Met Ser Gly Leu Gly 7505 7510 7515 7520 Ser Val Pro Ile Pro Leu Gln Gln Ala Arg Thr Leu Phe Asp Glu Val 7525 7530 7535 Gln Phe Lys Glu Lys Val Phe Leu Arg Gln Gln Gly Ser Tyr Ile Leu 7540 7545 7550 Thr Val Glu Ala Gly Lys Gln Leu Leu Leu Ser Ala Asp Ser Gly Ala 7555 7560 7565 Glu Ala Ala Leu Gln Ala Glu Leu Ala Glu Ile Gln Glu Lys Trp Lys 7570 7575 7580 Ser Ala Ser Met Arg Leu Glu Glu Gln Lys Lys Lys Leu Ala Phe Leu 7585 7590 7595 7600 Leu Lys Asp Trp Glu Lys Cys Glu Lys Gly Ile Ala Asp Ser Leu Glu 7605 7610 7615 Lys Leu Arg Thr Phe Lys Lys Lys Leu Ser Gln Ser Leu Pro Asp His 7620 7625 7630 His Glu Glu Leu His Ala Glu Gln Met Arg Cys Lys Glu Leu Glu Asn 7635 7640 7645 Ala Val Gly Ser Trp Thr Asp Asp Leu Thr Gln Leu Ser Leu Leu Lys 7650 7655 7660 Asp Thr Leu Ser Ala Tyr Ile Ser Ala Asp Asp Ile Ser Ile Leu Asn 7665 7670 7675 7680 Glu Arg Val Glu Leu Leu Gln Arg Gln Trp Glu Glu Leu Cys His Gln 7685 7690 7695 Leu Ser Leu Arg Arg Gln Gln Ile Gly Glu Arg Leu Asn Glu Trp Ala 7700 7705 7710 Val Phe Ser Glu Lys Asn Lys Glu Leu Cys Glu Trp Leu Thr Gln Met 7715 7720 7725 Glu Ser Lys Val Ser Gln Asn Gly Asp Ile Leu Ile Glu Glu Met Ile 7730 7735 7740 Glu Lys Leu Lys Lys Asp Tyr Gln Glu Glu Ile Ala Ile Ala Gln Glu 7745 7750 7755 7760 Asn Lys Ile Gln Leu Gln Gln Met Gly Glu Arg Leu Ala Lys Ala Ser 7765 7770 7775 His Glu Ser Lys Ala Ser Glu Ile Glu Tyr Lys Leu Gly Lys Val Asn 7780 7785 7790 Asp Arg Trp Gln His Leu Leu Asp Leu Ile Ala Ala Arg Val Lys Lys 7795 7800 7805 Leu Lys Glu Thr Leu Val Ala Val Gln Gln Leu Asp Lys Asn Met Ser 7810 7815 7820 Ser Leu Arg Thr Trp Leu Ala His Ile Glu Ser Glu Leu Ala Lys Pro 7825 7830 7835 7840 Ile Val Tyr Asp Ser Cys Asn Ser Glu Glu Ile Gln Arg Lys Leu Asn 7845 7850 7855 Glu Gln Gln Glu Leu Gln Arg Asp Ile Glu Lys His Ser Thr Gly Val 7860 7865 7870 Ala Ser Val Leu Asn Leu Cys Glu Val Leu Leu His Asp Cys Asp Ala 7875 7880 7885 Cys Ala Thr Asp Ala Glu Cys Asp Ser Ile Gln Gln Ala Thr Arg Asn 7890 7895 7900 Leu Asp Arg Arg Trp Arg Asn Ile Cys Ala Met Ser Met Glu Arg Arg 7905 7910 7915 7920 Leu Lys Ile Glu Glu Thr Trp Arg Leu Trp Gln Lys Phe Leu Asp Asp 7925 7930 7935 Tyr Ser Arg Phe Glu Asp Trp Leu Lys Ser Ser Glu Arg Thr Ala Ala 7940 7945 7950 Phe Pro Ser Ser Ser Gly Val Ile Tyr Thr Val Ala Lys Glu Glu Leu 7955 7960 7965 Lys Lys Phe Glu Ala Phe Gln Arg Gln Val His Glu Cys Leu Thr Gln 7970 7975 7980 Leu Glu Leu Ile Asn Lys Gln Tyr Arg Arg Leu Ala Arg Glu Asn Arg 7985 7990 7995 8000 Thr Asp Ser Ala Cys Ser Leu Lys Gln Met Val His Glu Gly Asn Gln 8005 8010 8015 Arg Trp Asp Asn Leu Gln Lys Arg Val Thr Ser Ile Leu Arg Arg Leu 8020 8025 8030 Lys His Phe Ile Gly Gln Arg Glu Glu Phe Glu Thr Ala Arg Asp Ser 8035 8040 8045 Ile Leu Val Trp Leu Thr Glu Met Asp Leu Gln Leu Thr Asn Ile Glu 8050 8055 8060 His Phe Ser Glu Cys Asp Val Gln Ala Lys Ile Lys Gln Leu Lys Ala 8065 8070 8075 8080 Phe Gln Gln Glu Ile Ser Leu Asn His Asn Lys Ile Glu Gln Ile Ile 8085 8090 8095 Ala Gln Gly Glu Gln Leu Ile Glu Lys Ser Glu Pro Leu Asp Ala Ala 8100 8105 8110 Ile Ile Glu Glu Glu Leu Asp Glu Leu Arg Arg Tyr Cys Gln Glu Val 8115 8120 8125 Phe Gly Arg Val Glu Arg Tyr His Lys Lys Leu Ile Arg Leu Pro Leu 8130 8135 8140 Pro Asp Asp Glu His Asp Leu Ser Asp Arg Glu Leu Glu Leu Glu Asp 8145 8150 8155 8160 Ser Ala Ala Leu Ser Asp Leu His Trp His Asp Arg Ser Ala Asp Ser 8165 8170 8175 Leu Leu Ser Pro Gln Pro Ser Ser Asn Leu Ser Leu Ser Leu Ala Gln 8180 8185 8190 Pro Leu Arg Ser Glu Arg Ser Gly Arg Asp Thr Pro Ala Ser Val Asp 8195 8200 8205 Ser Ile Pro Leu Glu Trp Asp His Asp Tyr Asp Leu Ser Arg Asp Leu 8210 8215 8220 Glu Ser Ala Met Ser Arg Ala Leu Pro Ser Glu Asp Glu Glu Gly Gln 8225 8230 8235 8240 Asp Asp Lys Asp Phe Tyr Leu Arg Gly Ala Val Ala Leu Ser Asp Val 8245 8250 8255 Met Ile Pro Glu Ser Pro Glu Ala Tyr Val Lys Leu Thr Glu Asn Ala 8260 8265 8270 Ile Lys Asn Thr Ser Gly Asp His Ser Ala Leu Glu Ser Gln Ile Arg 8275 8280 8285 Gln Leu Gly Lys Ala Leu Asp Asp Ser Arg Phe Gln Ile Gln Gln Thr 8290 8295 8300 Glu Asn Ile Ile Arg Ser Lys Thr Pro Thr Gly Pro Glu Leu Asp Thr 8305 8310 8315 8320 Ser Tyr Lys Gly Tyr Met Lys Leu Leu Gly Glu Cys Ser Ser Ser Ile 8325 8330 8335 Asp Ser Val Lys Arg Leu Glu His Lys Leu Lys Glu Glu Glu Glu Ser 8340 8345 8350 Leu Pro Gly Phe Val Asn Leu His Ser Thr Glu Thr Gln Thr Ala Gly 8355 8360 8365 Val Ile Asp Arg Trp Glu Leu Leu Gln Ala Gln Ala Leu Ser Lys Glu 8370 8375 8380 Leu Arg Met Lys Gln Asn Leu Gln Lys Trp Gln Gln Phe Asn Ser Asp 8385 8390 8395 8400 Leu Asn Ser Ile Trp Ala Trp Leu Gly Asp Thr Glu Glu Glu Leu Glu 8405 8410 8415 Gln Leu Gln Arg Leu Glu Leu Ser Thr Asp Ile Gln Thr Ile Glu Leu 8420 8425 8430 Gln Ile Lys Lys Leu Lys Glu Leu Gln Lys Ala Val Asp His Arg Lys 8435 8440 8445 Ala Ile Ile Leu Ser Ile Asn Leu Cys Ser Pro Glu Phe Thr Gln Ala 8450 8455 8460 Asp Ser Lys Glu Ser Arg Asp Leu Gln Asp Arg Leu Ser Gln Met Asn 8465 8470 8475 8480 Gly Arg Trp Asp Arg Val Cys Ser Leu Leu Glu Glu Trp Arg Gly Leu 8485 8490 8495 Leu Gln Asp Ala Leu Met Gln Cys Gln Gly Phe His Glu Met Ser His 8500 8505 8510 Gly Leu Leu Leu Met Leu Glu Asn Ile Asp Arg Arg Lys Asn Glu Ile 8515 8520 8525 Val Pro Ile Asp Ser Asn Leu Asp Ala Glu Ile Leu Gln Asp His His 8530 8535 8540 Lys Gln Leu Met Gln Ile Lys His Glu Leu Leu Glu Ser Gln Leu Arg 8545 8550 8555 8560 Val Ala Ser Leu Gln Asp Met Ser Cys Gln Leu Leu Val Asn Ala Glu 8565 8570 8575 Gly Thr Asp Cys Leu Glu Ala Lys Glu Lys Val His Val Ile Gly Asn 8580 8585 8590 Arg Leu Lys Leu Leu Leu Lys Glu Val Ser Arg His Ile Lys Glu Leu 8595 8600 8605 Glu Lys Leu Leu Asp Val Ser Ser Ser Gln Gln Asp Leu Ser Ser Trp 8610 8615 8620 Ser Ser Ala Asp Glu Leu Asp Thr Ser Gly Ser Val Ser Pro Thr Ser 8625 8630 8635 8640 Gly Arg Ser Thr Pro Asn Arg Gln Lys Thr Pro Arg Gly Lys Cys Ser 8645 8650 8655 Leu Ser Gln Pro Gly Pro Ser Val Ser Ser Pro His Ser Arg Ser Thr 8660 8665 8670 Lys Gly Gly Ser Asp Ser Ser Leu Ser Glu Pro Gly Pro Gly Arg Ser 8675 8680 8685 Gly Arg Gly Phe Leu Phe Arg Val Leu Arg Ala Ala Leu Pro Leu Gln 8690 8695 8700 Leu Leu Leu Leu Leu Leu Ile Gly Leu Ala Cys Leu Val Pro Met Ser 8705 8710 8715 8720 Glu Glu Asp Tyr Ser Cys Ala Leu Ser Asn Asn Phe Ala Arg Ser Phe 8725 8730 8735 His Pro Met Leu Arg Tyr Thr Asn Gly Pro Pro Pro Leu 8740 8745 <210> 97 <211> 299 <212> PRT <213> Homo sapiens <400> 97 Met Gly Thr Lys Ala Gln Val Glu Arg Lys Leu Leu Cys Leu Phe Ile 1 5 10 15 Leu Ala Ile Leu Leu Cys Ser Leu Ala Leu Gly Ser Val Thr Val His 20 25 30 Ser Ser Glu Pro Glu Val Arg Ile Pro Glu Asn Asn Pro Val Lys Leu 35 40 45 Ser Cys Ala Tyr Ser Gly Phe Ser Ser Pro Arg Val Glu Trp Lys Phe 50 55 60 Asp Gln Gly Asp Thr Thr Arg Leu Val Cys Tyr Asn Asn Lys Ile Thr 65 70 75 80 Ala Ser Tyr Glu Asp Arg Val Thr Phe Leu Pro Thr Gly Ile Thr Phe 85 90 95 Lys Ser Val Thr Arg Glu Asp Thr Gly Thr Tyr Thr Cys Met Val Ser 100 105 110 Glu Glu Gly Gly Asn Ser Tyr Gly Glu Val Lys Val Lys Leu Ile Val 115 120 125 Leu Val Pro Pro Ser Lys Pro Thr Val Asn Ile Pro Ser Ser Ala Thr 130 135 140 Ile Gly Asn Arg Ala Val Leu Thr Cys Ser Glu Gln Asp Gly Ser Pro 145 150 155 160 Pro Ser Glu Tyr Thr Trp Phe Lys Asp Gly Ile Val Met Pro Thr Asn 165 170 175 Pro Lys Ser Thr Arg Ala Phe Ser Asn Ser Ser Tyr Val Leu Asn Pro 180 185 190 Thr Thr Gly Glu Leu Val Phe Asp Pro Leu Ser Ala Ser Asp Thr Gly 195 200 205 Glu Tyr Ser Cys Glu Ala Arg Asn Gly Tyr Gly Thr Pro Met Thr Ser 210 215 220 Asn Ala Val Arg Met Glu Ala Val Glu Arg Asn Val Gly Val Ile Val 225 230 235 240 Ala Ala Val Leu Val Thr Leu Ile Leu Leu Gly Ile Leu Val Phe Gly 245 250 255 Ile Trp Phe Ala Tyr Ser Arg Gly His Phe Asp Arg Thr Lys Lys Gly 260 265 270 Thr Ser Ser Lys Lys Val Ile Tyr Ser Gln Pro Ser Ala Arg Ser Glu 275 280 285 Gly Glu Phe Lys Gln Thr Ser Ser Phe Leu Val 290 295 <210> 98 <211> 2448 <212> PRT <213> Homo sapiens <400> 98 Met Ser Val Gly Arg Arg Lys Leu Ala Leu Leu Trp Ala Leu Ala Leu 1 5 10 15 Ala Leu Ala Cys Thr Arg His Thr Gly His Ala Gln Asp Gly Ser Ser 20 25 30 Glu Ser Ser Tyr Lys His His Pro Ala Leu Ser Pro Ile Ala Arg Gly 35 40 45 Pro Ser Gly Val Pro Leu Arg Gly Ala Thr Val Phe Pro Ser Leu Arg 50 55 60 Thr Ile Pro Val Val Arg Ala Ser Asn Pro Ala His Asn Gly Arg Val 65 70 75 80 Cys Ser Thr Trp Gly Ser Phe His Tyr Lys Thr Phe Asp Gly Asp Val 85 90 95 Phe Arg Phe Pro Gly Leu Cys Asn Tyr Val Phe Ser Glu His Cys Gly 100 105 110 Ala Ala Tyr Glu Asp Phe Asn Ile Gln Leu Arg Arg Ser Gln Glu Ser 115 120 125 Ala Ala Pro Thr Leu Ser Arg Val Leu Met Lys Val Asp Gly Val Val 130 135 140 Ile Gln Leu Thr Lys Gly Ser Val Leu Val Asn Gly His Pro Val Leu 145 150 155 160 Leu Pro Phe Ser Gln Ser Gly Val Leu Ile Gln Gln Ser Ser Ser Tyr 165 170 175 Thr Lys Val Glu Ala Arg Leu Gly Leu Val Leu Met Trp Asn His Asp 180 185 190 Asp Ser Leu Leu Leu Glu Leu Asp Thr Lys Tyr Ala Asn Lys Thr Cys 195 200 205 Gly Leu Cys Gly Asp Phe Asn Gly Met Pro Val Val Ser Glu Leu Leu 210 215 220 Ser His Asn Thr Lys Leu Thr Pro Met Glu Phe Gly Asn Leu Gln Lys 225 230 235 240 Met Asp Asp Pro Thr Glu Gln Cys Gln Asp Pro Val Pro Glu Pro Pro 245 250 255 Arg Asn Cys Ser Thr Gly Phe Gly Ile Cys Glu Glu Leu Leu His Gly 260 265 270 Gln Leu Phe Ser Gly Cys Val Ala Leu Val Asp Val Gly Ser Tyr Leu 275 280 285 Glu Ala Cys Arg Gln Asp Leu Cys Phe Cys Glu Asp Thr Asp Leu Leu 290 295 300 Ser Cys Val Cys His Thr Leu Ala Glu Tyr Ser Arg Gln Cys Thr His 305 310 315 320 Ala Gly Gly Leu Pro Gln Asp Trp Arg Gly Pro Asp Phe Cys Pro Gln 325 330 335 Lys Cys Pro Asn Asn Met Gln Tyr His Glu Cys Arg Ser Pro Cys Ala 340 345 350 Asp Thr Cys Ser Asn Gln Glu His Ser Arg Ala Cys Glu Asp His Cys 355 360 365 Val Ala Gly Cys Phe Cys Pro Glu Gly Thr Val Leu Asp Asp Ile Gly 370 375 380 Gln Thr Gly Cys Val Pro Val Ser Lys Cys Ala Cys Val Tyr Asn Gly 385 390 395 400 Ala Ala Tyr Ala Pro Gly Ala Thr Tyr Ser Thr Asp Cys Thr Asn Cys 405 410 415 Thr Cys Ser Gly Gly Arg Trp Ser Cys Gln Glu Val Pro Cys Pro Asp 420 425 430 Thr Cys Ser Val Leu Gly Gly Ala His Phe Ser Thr Phe Asp Gly Lys 435 440 445 Gln Tyr Thr Val His Gly Asp Cys Ser Tyr Val Leu Thr Lys Pro Cys 450 455 460 Asp Ser Ser Ala Phe Thr Val Leu Ala Glu Leu Arg Arg Cys Gly Leu 465 470 475 480 Thr Asp Ser Glu Thr Cys Leu Lys Ser Val Thr Leu Ser Leu Asp Gly 485 490 495 Ala Gln Thr Val Val Val Ile Lys Ala Ser Gly Glu Val Phe Leu Asn 500 505 510 Gln Ile Tyr Thr Gln Leu Pro Ile Ser Ala Ala Asn Val Thr Ile Phe 515 520 525 Arg Pro Ser Thr Phe Phe Ile Ile Ala Gln Thr Ser Leu Gly Leu Gln 530 535 540 Leu Asn Leu Gln Pro Val Pro Thr Met Gln Leu Phe Met Gln Leu Ala 545 550 555 560 Pro Lys Leu Arg Gly Gln Thr Cys Gly Leu Cys Gly Asn Phe Asn Ser 565 570 575 Ile Gln Ala Asp Asp Phe Arg Thr Leu Ser Gly Val Val Glu Ala Thr 580 585 590 Ala Ala Ala Phe Phe Asn Thr Phe Lys Thr Gln Ala Ala Cys Pro Asn 595 600 605 Ile Arg Asn Ser Phe Glu Asp Pro Cys Ser Leu Ser Val Glu Asn Glu 610 615 620 Lys Tyr Ala Gln His Trp Cys Ser Gln Leu Thr Asp Ala Asp Gly Pro 625 630 635 640 Phe Gly Arg Cys His Ala Ala Val Lys Pro Gly Thr Tyr Tyr Ser Asn 645 650 655 Cys Val Phe Asp Thr Cys Asn Cys Glu Arg Ser Glu Asp Cys Leu Cys 660 665 670 Ala Ala Leu Ser Ser Tyr Val His Ala Cys Ala Ala Lys Gly Val Gln 675 680 685 Leu Gly Gly Trp Arg Asp Gly Val Cys Thr Lys Pro Met Thr Thr Cys 690 695 700 Pro Lys Ser Met Thr Tyr His Tyr His Val Ser Thr Cys Gln Pro Thr 705 710 715 720 Cys Arg Ser Leu Ser Glu Gly Asp Ile Thr Cys Ser Val Gly Phe Ile 725 730 735 Pro Val Asp Gly Cys Ile Cys Pro Lys Gly Thr Phe Leu Asp Asp Thr 740 745 750 Gly Lys Cys Val Gln Ala Ser Asn Cys Pro Cys Tyr His Arg Gly Ser 755 760 765 Met Ile Pro Asn Gly Glu Ser Val His Asp Ser Gly Ala Ile Cys Thr 770 775 780 Cys Thr His Gly Lys Leu Ser Cys Ile Gly Gly Gln Ala Pro Ala Pro 785 790 795 800 Val Cys Ala Ala Pro Met Val Phe Phe Asp Cys Arg Asn Ala Thr Pro 805 810 815 Gly Asp Thr Gly Ala Gly Cys Gln Lys Ser Cys His Thr Leu Asp Met 820 825 830 Thr Cys Tyr Ser Pro Gln Cys Val Pro Gly Cys Val Cys Pro Asp Gly 835 840 845 Leu Val Ala Asp Gly Glu Gly Gly Cys Ile Thr Ala Glu Asp Cys Pro 850 855 860 Cys Val His Asn Glu Ala Ser Tyr Arg Ala Gly Gln Thr Ile Arg Val 865 870 875 880 Gly Cys Asn Thr Cys Thr Cys Asp Ser Arg Met Trp Arg Cys Thr Asp 885 890 895 Asp Pro Cys Leu Ala Thr Cys Ala Val Tyr Gly Asp Gly His Tyr Leu 900 905 910 Thr Phe Asp Gly Gln Ser Tyr Ser Phe Asn Gly Asp Cys Glu Tyr Thr 915 920 925 Leu Val Gln Asn His Cys Gly Gly Lys Asp Ser Thr Gln Asp Ser Phe 930 935 940 Arg Val Val Thr Glu Asn Val Pro Cys Gly Thr Thr Gly Thr Thr Cys 945 950 955 960 Ser Lys Ala Ile Lys Ile Phe Leu Gly Gly Phe Glu Leu Lys Leu Ser 965 970 975 His Gly Lys Val Glu Val Ile Gly Thr Asp Glu Ser Gln Glu Val Pro 980 985 990 Tyr Thr Ile Gln Gln Met Gly Ile Tyr Leu Val Val Asp Thr Asp Ile 995 1000 1005 Gly Leu Val Leu Leu Trp Asp Lys Lys Thr Ser Ile Phe Ile Asn Leu 1010 1015 1020 Ser Pro Glu Phe Lys Gly Arg Val Cys Gly Leu Cys Gly Asn Phe Asp 1025 1030 1035 1040 Asp Ile Ala Val Asn Asp Phe Ala Thr Arg Ser Arg Ser Val Val Gly 1045 1050 1055 Asp Val Leu Glu Phe Gly Asn Ser Trp Lys Leu Ser Pro Ser Cys Pro 1060 1065 1070 Asp Ala Leu Ala Pro Lys Asp Pro Cys Thr Ala Asn Pro Phe Arg Lys 1075 1080 1085 Ser Trp Ala Gln Lys Gln Cys Ser Ile Leu His Gly Pro Thr Phe Ala 1090 1095 1100 Ala Cys His Ala His Val Glu Pro Ala Arg Tyr Tyr Glu Ala Cys Val 1105 1110 1115 1120 Asn Asp Ala Cys Ala Cys Asp Ser Gly Gly Asp Cys Glu Cys Phe Cys 1125 1130 1135 Thr Ala Val Ala Ala Tyr Ala Gln Ala Cys His Glu Val Gly Leu Cys 1140 1145 1150 Val Cys Leu Arg Thr Pro Ser Ile Cys Pro Leu Phe Cys Asp Tyr Tyr 1155 1160 1165 Asn Pro Glu Gly Gln Cys Glu Trp His Tyr Gln Pro Cys Gly Val Pro 1170 1175 1180 Cys Leu Arg Thr Cys Arg Asn Pro Arg Gly Asp Cys Leu Arg Asp Val 1185 1190 1195 1200 Arg Gly Leu Glu Gly Cys Tyr Pro Lys Cys Pro Pro Glu Ala Pro Ile 1205 1210 1215 Phe Asp Glu Asp Lys Met Gln Cys Val Ala Thr Cys Pro Thr Pro Pro 1220 1225 1230 Leu Pro Pro Arg Cys His Val His Gly Lys Ser Tyr Arg Pro Gly Ala 1235 1240 1245 Val Val Pro Ser Asp Lys Asn Cys Gln Ser Cys Leu Cys Thr Glu Arg 1250 1255 1260 Gly Val Glu Cys Thr Tyr Lys Ala Glu Ala Cys Val Cys Thr Tyr Asn 1265 1270 1275 1280 Gly Gln Arg Phe His Pro Gly Asp Val Ile Tyr His Thr Thr Asp Gly 1285 1290 1295 Thr Gly Gly Cys Ile Ser Ala Arg Cys Gly Ala Asn Gly Thr Ile Glu 1300 1305 1310 Arg Arg Val Tyr Pro Cys Ser Pro Thr Thr Pro Val Pro Pro Thr Thr 1315 1320 1325 Phe Ser Phe Ser Thr Pro Pro Leu Val Val Ser Ser Thr His Thr Pro 1330 1335 1340 Ser Asn Gly Pro Ser Ser Ala His Thr Gly Pro Pro Ser Ser Ala Trp 1345 1350 1355 1360 Pro Thr Thr Ala Gly Thr Ser Pro Arg Thr Arg Leu Pro Thr Ala Ser 1365 1370 1375 Ala Ser Leu Pro Pro Val Cys Gly Glu Lys Cys Leu Trp Ser Pro Trp 1380 1385 1390 Met Asp Val Ser Arg Pro Gly Arg Gly Thr Asp Ser Gly Asp Phe Asp 1395 1400 1405 Thr Leu Glu Asn Leu Arg Ala His Gly Tyr Arg Val Cys Glu Ser Pro 1410 1415 1420 Arg Ser Val Glu Cys Arg Ala Glu Asp Ala Pro Gly Val Pro Leu Arg 1425 1430 1435 1440 Ala Leu Gly Gln Arg Val Gln Cys Ser Pro Asp Val Gly Leu Thr Cys 1445 1450 1455 Arg Asn Arg Glu Gln Ala Ser Gly Leu Cys Tyr Asn Tyr Gln Ile Arg 1460 1465 1470 Val Gln Cys Cys Thr Pro Leu Pro Cys Ser Thr Ser Ser Ser Pro Ala 1475 1480 1485 Gln Thr Thr Pro Pro Thr Thr Ser Lys Thr Thr Glu Thr Arg Ala Ser 1490 1495 1500 Gly Ser Ser Ala Pro Ser Ser Thr Pro Gly Thr Val Ser Leu Ser Thr 1505 1510 1515 1520 Ala Arg Thr Thr Pro Ala Pro Gly Thr Ala Thr Ser Val Lys Lys Thr 1525 1530 1535 Phe Ser Thr Pro Ser Pro Pro Pro Val Pro Ala Thr Ser Thr Ser Ser 1540 1545 1550 Met Ser Thr Thr Ala Pro Gly Thr Ser Val Val Ser Ser Lys Pro Thr 1555 1560 1565 Pro Thr Glu Pro Ser Thr Ser Ser Cys Leu Gln Glu Leu Cys Thr Trp 1570 1575 1580 Thr Glu Trp Ile Asp Gly Ser Tyr Pro Ala Pro Gly Ile Asn Gly Gly 1585 1590 1595 1600 Asp Phe Asp Thr Phe Gln Asn Leu Arg Asp Glu Gly Tyr Thr Phe Cys 1605 1610 1615 Glu Ser Pro Arg Ser Val Gln Cys Arg Ala Glu Ser Phe Pro Asn Thr 1620 1625 1630 Pro Leu Ala Asp Leu Gly Gln Asp Val Ile Cys Ser His Thr Glu Gly 1635 1640 1645 Leu Ile Cys Leu Asn Lys Asn Gln Leu Pro Pro Ile Cys Tyr Asn Tyr 1650 1655 1660 Glu Ile Arg Ile Gln Cys Cys Glu Thr Val Asn Val Cys Arg Asp Ile 1665 1670 1675 1680 Thr Arg Leu Pro Lys Thr Val Ala Thr Thr Arg Pro Thr Pro His Pro 1685 1690 1695 Thr Gly Ala Gln Thr Gln Thr Thr Phe Thr Thr His Met Pro Ser Ala 1700 1705 1710 Ser Thr Glu Gln Pro Thr Ala Thr Ser Arg Gly Gly Pro Thr Ala Thr 1715 1720 1725 Ser Val Thr Gln Gly Thr His Thr Thr Leu Val Thr Arg Asn Cys His 1730 1735 1740 Pro Arg Cys Thr Trp Thr Lys Trp Phe Asp Val Asp Phe Pro Ser Pro 1745 1750 1755 1760 Gly Pro His Gly Gly Asp Lys Glu Thr Tyr Asn Asn Ile Ile Arg Ser 1765 1770 1775 Gly Glu Lys Ile Cys Arg Arg Pro Glu Glu Ile Thr Arg Val Gln Cys 1780 1785 1790 Arg Ala Lys Ser His Pro Glu Val Ser Ile Glu His Leu Gly Gln Val 1795 1800 1805 Val Gln Cys Ser Arg Glu Glu Gly Leu Val Cys Arg Asn Gln Asp Gln 1810 1815 1820 Gln Gly Pro Phe Lys Met Cys Leu Asn Tyr Glu Val Arg Val Leu Cys 1825 1830 1835 1840 Cys Glu Thr Pro Arg Gly Cys His Met Thr Ser Thr Pro Gly Ser Thr 1845 1850 1855 Ser Ser Ser Pro Ala Gln Thr Thr Pro Ser Thr Thr Ser Lys Thr Thr 1860 1865 1870 Glu Ile Gln Ala Ser Gly Ser Ser Ala Pro Ser Ser Thr Pro Gly Thr 1875 1880 1885 Val Ser Leu Ser Thr Ala Arg Thr Thr Pro Ala Pro Gly Thr Ala Thr 1890 1895 1900 Ser Val Lys Lys Thr Phe Ser Thr Pro Ser Pro Pro Pro Val Pro Ala 1905 1910 1915 1920 Thr Ser Thr Ser Ser Met Ser Thr Thr Ala Pro Gly Thr Ser Val Val 1925 1930 1935 Ser Ser Lys Pro Thr Pro Thr Glu Pro Ser Thr Ser Ser Cys Leu Gln 1940 1945 1950 Glu Leu Cys Thr Trp Thr Glu Trp Ile Asp Gly Ser Tyr Pro Ala Pro 1955 1960 1965 Gly Ile Asn Gly Gly Asp Phe Asp Thr Phe Gln Asn Leu Arg Asp Glu 1970 1975 1980 Gly Tyr Thr Phe Cys Glu Ser Pro Arg Ser Val Gln Cys Arg Ala Glu 1985 1990 1995 2000 Ser Phe Pro Asn Thr Pro Leu Gly Arg Leu Gly Gln Asp Val Ile Cys 2005 2010 2015 Ser His Thr Glu Gly Leu Ile Cys Leu Asn Lys Asn Gln Leu Pro Pro 2020 2025 2030 Ile Cys Tyr Asn Tyr Glu Ile Arg Ile Gln Cys Cys Glu Thr Val Asn 2035 2040 2045 Val Cys Arg Asp Ile Thr Arg Pro Pro Lys Thr Val Ala Thr Thr Arg 2050 2055 2060 Pro Thr Pro His Pro Thr Gly Ala Gln Thr Gln Thr Thr Phe Thr Thr 2065 2070 2075 2080 His Met Pro Ser Ala Ser Thr Glu Gln Pro Thr Ala Thr Ser Arg Gly 2085 2090 2095 Gly Pro Thr Ala Thr Ser Val Thr Gln Gly Thr His Thr Thr Pro Val 2100 2105 2110 Thr Arg Asn Cys His Pro Arg Cys Thr Trp Thr Thr Trp Phe Asp Val 2115 2120 2125 Asp Phe Pro Ser Pro Gly Pro His Gly Gly Asp Lys Glu Thr Tyr Asn 2130 2135 2140 Asn Ile Ile Arg Ser Gly Glu Lys Ile Cys Arg Arg Pro Glu Glu Ile 2145 2150 2155 2160 Thr Arg Leu Gln Cys Arg Ala Lys Ser His Pro Glu Val Ser Ile Glu 2165 2170 2175 His Leu Gly Gln Val Val Gln Cys Ser Arg Glu Glu Gly Leu Val Cys 2180 2185 2190 Arg Asn Gln Asp Gln Gln Gly Pro Phe Lys Met Cys Leu Asn Ile Glu 2195 2200 2205 Val Arg Val Leu Cys Cys Glu Thr Pro Lys Gly Cys Pro Val Thr Ser 2210 2215 2220 Thr Pro Val Thr Ala Pro Ser Thr Pro Ser Gly Arg Ala Ile Ser Pro 2225 2230 2235 2240 Thr Gln Ser Thr Ser Ser Trp Gln Lys Ser Arg Thr Thr Thr Leu Val 2245 2250 2255 Thr Thr Ser Thr Thr Ser Thr Pro Gln Thr Ser Thr Thr Tyr Ala His 2260 2265 2270 Thr Thr Ser Thr Thr Ser Ala Pro Thr Ala Arg Thr Thr Ser Ala Pro 2275 2280 2285 Thr Thr Ser Thr Thr Ser Val Pro Thr Thr Ser Thr Ile Ser Gly Pro 2290 2295 2300 Lys Thr Thr Pro Ser Pro Val Pro Thr Thr Ser Thr Thr Ser Ala Ala 2305 2310 2315 2320 Thr Thr Ser Thr Ile Ser Ala Pro Thr Thr Ser Thr Thr Ser Val Pro 2325 2330 2335 Gly Thr Thr Pro Ser Pro Val Leu Thr Thr Ser Thr Thr Ser Ala Pro 2340 2345 2350 Thr Thr Arg Thr Thr Ser Ala Ser Pro Ala Gly Thr Thr Ser Gly Pro 2355 2360 2365 Gly Asn Thr Pro Ser Pro Val Pro Thr Thr Ser Thr Ile Ser Ala Pro 2370 2375 2380 Thr Thr Ser Ile Thr Ser Ala Pro Thr Thr Ser Thr Thr Ser Ala Pro 2385 2390 2395 2400 Thr Ser Ser Thr Thr Ser Gly Pro Gly Thr Thr Pro Ser Pro Val Pro 2405 2410 2415 Thr Thr Ser Ile Thr Ser Ala Pro Thr Thr Ser Thr Thr Ser Ala Pro 2420 2425 2430 Thr Thr Ser Thr Thr Ser Ala Pro Thr Thr Ser Thr Thr Ser Ala Pro 2435 2440 2445 <210> 99 <211> 890 <212> PRT <213> Homo sapiens <400> 99 Met Glu Gly Gly Gly Lys Pro Asn Ser Ser Ser Asn Ser Arg Asp Asp 1 5 10 15 Gly Asn Ser Val Phe Pro Ala Lys Ala Ser Ala Thr Gly Ala Gly Pro 20 25 30 Ala Ala Ala Glu Lys Arg Leu Gly Thr Pro Pro Gly Gly Gly Gly Ala 35 40 45 Gly Ala Lys Glu His Gly Asn Ser Val Cys Phe Lys Val Asp Gly Gly 50 55 60 Gly Gly Gly Gly Gly Gly Gly Gly Gly Gly Glu Glu Pro Ala Gly Gly 65 70 75 80 Phe Glu Asp Ala Glu Gly Pro Arg Arg Gln Tyr Gly Phe Met Gln Arg 85 90 95 Gln Phe Thr Ser Met Leu Gln Pro Gly Val Asn Lys Phe Ser Leu Arg 100 105 110 Met Phe Gly Ser Gln Lys Ala Val Glu Lys Glu Gln Glu Arg Val Lys 115 120 125 Thr Ala Gly Phe Trp Ile Ile His Pro Tyr Ser Asp Phe Arg Phe Tyr 130 135 140 Trp Asp Leu Ile Met Leu Ile Met Met Val Gly Asn Leu Val Ile Ile 145 150 155 160 Pro Val Gly Ile Thr Phe Phe Thr Glu Gln Thr Thr Thr Pro Trp Ile 165 170 175 Ile Phe Asn Val Ala Ser Asp Thr Val Phe Leu Leu Asp Leu Ile Met 180 185 190 Asn Phe Arg Thr Gly Thr Val Asn Glu Asp Ser Ser Glu Ile Ile Leu 195 200 205 Asp Pro Lys Val Ile Lys Met Asn Tyr Leu Lys Ser Trp Phe Val Val 210 215 220 Asp Phe Ile Ser Ser Ile Pro Val Asp Tyr Ile Phe Leu Ile Val Glu 225 230 235 240 Lys Gly Met Asp Ser Glu Val Tyr Lys Thr Ala Arg Ala Leu Arg Ile 245 250 255 Val Arg Phe Thr Lys Ile Leu Ser Leu Leu Arg Leu Leu Arg Leu Ser 260 265 270 Arg Leu Ile Arg Tyr Ile His Gln Trp Glu Glu Ile Phe His Met Thr 275 280 285 Tyr Asp Leu Ala Ser Ala Val Val Arg Ile Phe Asn Leu Ile Gly Met 290 295 300 Met Leu Leu Leu Cys His Trp Asp Gly Cys Leu Gln Phe Leu Val Pro 305 310 315 320 Leu Leu Gln Asp Phe Pro Pro Asp Cys Trp Val Ser Leu Asn Glu Met 325 330 335 Val Asn Asp Ser Trp Gly Lys Gln Tyr Ser Tyr Ala Leu Phe Lys Ala 340 345 350 Met Ser His Met Leu Cys Ile Gly Tyr Gly Ala Gln Ala Pro Val Ser 355 360 365 Met Ser Asp Leu Trp Ile Thr Met Leu Ser Met Ile Val Gly Ala Thr 370 375 380 Cys Tyr Ala Met Phe Val Gly His Ala Thr Ala Leu Ile Gln Ser Leu 385 390 395 400 Asp Ser Ser Arg Arg Gln Tyr Gln Glu Lys Tyr Lys Gln Val Glu Gln 405 410 415 Tyr Met Ser Phe His Lys Leu Pro Ala Asp Met Arg Gln Lys Ile His 420 425 430 Asp Tyr Tyr Glu His Arg Tyr Gln Gly Lys Ile Phe Asp Glu Glu Asn 435 440 445 Ile Leu Asn Glu Leu Asn Asp Pro Leu Arg Glu Glu Ile Val Asn Phe 450 455 460 Asn Cys Arg Lys Leu Val Ala Thr Met Pro Leu Phe Ala Asn Ala Asp 465 470 475 480 Pro Asn Phe Val Thr Ala Met Leu Ser Lys Leu Arg Phe Glu Val Phe 485 490 495 Gln Pro Gly Asp Tyr Ile Ile Arg Glu Gly Ala Val Gly Lys Lys Met 500 505 510 Tyr Phe Ile Gln His Gly Val Ala Gly Val Ile Thr Lys Ser Ser Lys 515 520 525 Glu Met Lys Leu Thr Asp Gly Ser Tyr Phe Gly Glu Ile Cys Leu Leu 530 535 540 Thr Lys Gly Arg Arg Thr Ala Ser Val Arg Ala Asp Thr Tyr Cys Arg 545 550 555 560 Leu Tyr Ser Leu Ser Val Asp Asn Phe Asn Glu Val Leu Glu Glu Tyr 565 570 575 Pro Met Met Arg Arg Ala Phe Glu Thr Val Ala Ile Asp Arg Leu Asp 580 585 590 Arg Ile Gly Lys Lys Asn Ser Ile Leu Leu Gln Lys Phe Gln Lys Asp 595 600 605 Leu Asn Thr Gly Val Phe Asn Asn Gln Glu Asn Glu Ile Leu Lys Gln 610 615 620 Ile Val Lys His Asp Arg Glu Met Val Gln Ala Ile Ala Pro Ile Asn 625 630 635 640 Tyr Pro Gln Met Thr Thr Leu Asn Ser Thr Ser Ser Thr Thr Thr Pro 645 650 655 Thr Ser Arg Met Arg Thr Gln Ser Pro Pro Val Tyr Thr Ala Thr Ser 660 665 670 Leu Ser His Ser Asn Leu His Ser Pro Ser Pro Ser Thr Gln Thr Pro 675 680 685 Gln Pro Ser Ala Ile Leu Ser Pro Cys Ser Tyr Thr Thr Ala Val Cys 690 695 700 Ser Pro Pro Val Gln Ser Pro Leu Ala Ala Arg Thr Phe His Tyr Ala 705 710 715 720 Ser Pro Thr Ala Ser Gln Leu Ser Leu Met Gln Gln Gln Pro Gln Gln 725 730 735 Gln Val Gln Gln Ser Gln Pro Pro Gln Thr Gln Pro Gln Gln Pro Ser 740 745 750 Pro Gln Pro Gln Thr Pro Gly Ser Ser Thr Pro Lys Asn Glu Val His 755 760 765 Lys Ser Thr Gln Ala Leu His Asn Thr Asn Leu Thr Arg Glu Val Arg 770 775 780 Pro Phe Ser Ala Trp Gln Pro Ser Leu Pro His Glu Val Ser Thr Leu 785 790 795 800 Ile Ser Arg Pro His Pro Thr Val Gly Glu Ser Leu Ala Ser Ile Pro 805 810 815 Gln Pro Val Thr Ala Val Pro Gly Thr Gly Leu Gln Ala Gly Gly Arg 820 825 830 Ser Thr Val Pro Gln Arg Val Thr Leu Phe Arg Gln Met Ser Ser Gly 835 840 845 Ala Ile Pro Pro Asn Arg Gly Val Pro Pro Ala Pro Pro Pro Pro Ala 850 855 860 Ala Ala Leu Pro Arg Glu Ser Ser Ser Val Leu Asn Thr Asp Pro Asp 865 870 875 880 Ala Glu Lys Pro Arg Phe Ala Ser Asn Leu 885 890 <210> 100 <211> 3925 <212> PRT <213> Homo sapiens <400> 100 Gly Asn Glu Val Ser Leu Glu Gly Gly Ala Gly Asp Gly Pro Leu Pro 1 5 10 15 Pro Gly Gly Ala Gly Pro Gly Pro Gly Pro Gly Pro Gly Pro Gly Ala 20 25 30 Gly Lys Pro Pro Ser Ala Pro Ala Gly Gly Gly Gln Leu Pro Ala Ala 35 40 45 Gly Ala Ala Arg Ser Thr Ala Val Pro Pro Val Pro Gly Pro Gly Pro 50 55 60 Gly Pro Gly Pro Gly Pro Gly Pro Gly Ser Thr Ser Arg Arg Leu Asp 65 70 75 80 Pro Lys Glu Pro Leu Gly Asn Gln Arg Ala Ala Ser Pro Thr Pro Lys 85 90 95 Gln Ala Ser Ala Thr Thr Pro Gly His Glu Ser Pro Arg Glu Thr Arg 100 105 110 Ala Gln Gly Pro Ala Gly Gln Glu Ala Asp Gly Pro Arg Arg Thr Leu 115 120 125 Gln Val Asp Ser Arg Thr Gln Arg Ser Gly Arg Ser Pro Ser Val Ser 130 135 140 Pro Asp Arg Gly Ser Thr Pro Thr Ser Pro Tyr Ser Val Pro Gln Ile 145 150 155 160 Ala Pro Leu Pro Ser Ser Thr Leu Cys Pro Ile Cys Lys Thr Ser Asp 165 170 175 Leu Thr Ser Thr Pro Ser Gln Pro Asn Phe Asn Thr Cys Thr Gln Cys 180 185 190 His Asn Lys Val Cys Asn Gln Cys Gly Phe Asn Pro Asn Pro His Leu 195 200 205 Thr Gln Val Lys Glu Trp Leu Cys Leu Asn Cys Gln Met Gln Arg Ala 210 215 220 Leu Gly Met Asp Met Thr Thr Ala Pro Arg Ser Lys Ser Gln Gln Gln 225 230 235 240 Leu His Ser Pro Ala Leu Ser Pro Ala His Ser Pro Ala Lys Gln Pro 245 250 255 Leu Gly Lys Pro Asp Gln Glu Arg Ser Arg Gly Pro Gly Gly Pro Gln 260 265 270 Pro Gly Ser Arg Gln Ala Glu Thr Ala Arg Ala Thr Ser Val Pro Gly 275 280 285 Pro Ala Gln Ala Ala Ala Pro Pro Glu Val Gly Arg Val Ser Pro Gln 290 295 300 Pro Pro Gln Pro Thr Lys Pro Ser Thr Ala Glu Pro Arg Pro Pro Ala 305 310 315 320 Gly Glu Ala Pro Ala Lys Ser Ala Thr Ala Val Pro Ala Gly Leu Gly 325 330 335 Ala Thr Glu Gln Thr Gln Glu Gly Leu Thr Gly Lys Leu Phe Gly Leu 340 345 350 Gly Ala Ser Leu Leu Thr Gln Ala Ser Thr Leu Met Ser Val Gln Pro 355 360 365 Glu Ala Asp Thr Gln Gly Gln Pro Ala Pro Ser Lys Gly Thr Pro Lys 370 375 380 Ile Val Phe Asn Asp Ala Ser Lys Glu Ala Gly Pro Lys Pro Leu Gly 385 390 395 400 Ser Gly Pro Gly Pro Gly Pro Ala Pro Gly Ala Lys Thr Glu Pro Gly 405 410 415 Ala Arg Met Gly Pro Gly Ser Gly Pro Gly Ala Leu Pro Lys Thr Gly 420 425 430 Gly Thr Thr Ser Pro Lys His Gly Arg Ala Glu His Gln Ala Ala Ser 435 440 445 Lys Ala Ala Ala Lys Pro Lys Thr Met Pro Lys Glu Arg Ala Ile Cys 450 455 460 Pro Leu Cys Gln Ala Glu Leu Asn Val Gly Ser Lys Ser Pro Ala Asn 465 470 475 480 Tyr Asn Thr Cys Thr Thr Cys Arg Leu Gln Val Cys Asn Leu Cys Gly 485 490 495 Phe Asn Pro Thr Pro His Leu Val Glu Lys Thr Glu Trp Leu Cys Leu 500 505 510 Asn Cys Gln Thr Lys Arg Leu Leu Glu Gly Ser Leu Gly Glu Pro Thr 515 520 525 Pro Leu Pro Pro Pro Thr Ser Gln Gln Pro Pro Val Gly Ala Pro His 530 535 540 Arg Ala Ser Gly Thr Ser Pro Leu Lys Gln Lys Gly Pro Gln Gly Leu 545 550 555 560 Gly Gln Pro Ser Gly Pro Leu Pro Ala Lys Ala Ser Pro Leu Ser Thr 565 570 575 Lys Ala Ser Pro Leu Pro Ser Lys Ala Ser Pro Gln Ala Lys Pro Leu 580 585 590 Arg Ala Ser Glu Pro Ser Lys Thr Pro Ser Ser Val Gln Glu Lys Lys 595 600 605 Thr Arg Val Pro Thr Lys Ala Glu Pro Met Pro Lys Pro Pro Pro Glu 610 615 620 Thr Thr Pro Thr Pro Ala Thr Pro Lys Val Lys Ser Gly Val Arg Arg 625 630 635 640 Ala Glu Pro Ala Thr Pro Val Val Lys Ala Val Pro Glu Ala Pro Lys 645 650 655 Gly Gly Glu Ala Glu Asp Leu Val Gly Lys Pro Tyr Ser Gln Asp Ala 660 665 670 Ser Arg Ser Pro Gln Ser Leu Ser Asp Thr Gly Tyr Ser Ser Asp Gly 675 680 685 Ile Ser Ser Ser Gln Ser Glu Ile Thr Gly Val Val Gln Gln Glu Val 690 695 700 Glu Gln Leu Asp Ser Ala Gly Val Thr Gly Pro His Pro Pro Ser Pro 705 710 715 720 Ser Glu Ile His Lys Val Gly Ser Ser Met Arg Pro Leu Leu Gln Ala 725 730 735 Gln Gly Leu Ala Pro Ser Glu Arg Ser Lys Pro Leu Ser Ser Gly Thr 740 745 750 Gly Glu Glu Gln Lys Gln Arg Pro His Ser Leu Ser Ile Thr Pro Glu 755 760 765 Ala Phe Asp Ser Asp Glu Glu Leu Glu Asp Ile Leu Glu Glu Asp Glu 770 775 780 Asp Ser Ala Glu Trp Arg Arg Arg Arg Glu Gln Gln Asp Thr Ala Glu 785 790 795 800 Ser Ser Asp Asp Phe Gly Ser Gln Leu Arg His Asp Tyr Val Glu Asp 805 810 815 Ser Ser Glu Gly Gly Leu Ser Pro Leu Pro Pro Gln Pro Pro Ala Arg 820 825 830 Ala Ala Glu Leu Thr Asp Glu Asp Phe Met Arg Arg Gln Ile Leu Glu 835 840 845 Met Ser Ala Glu Glu Asp Asn Leu Glu Glu Asp Asp Thr Ala Thr Ser 850 855 860 Gly Arg Gly Leu Ala Lys His Gly Thr Gln Lys Gly Gly Pro Arg Pro 865 870 875 880 Arg Pro Glu Pro Ser Gln Glu Pro Ala Ala Leu Pro Lys Arg Arg Leu 885 890 895 Pro His Asn Ala Thr Thr Gly Tyr Glu Glu Leu Leu Pro Glu Gly Gly 900 905 910 Ser Ala Glu Ala Thr Asp Gly Ser Gly Thr Leu Gln Gly Gly Leu Arg 915 920 925 Arg Phe Lys Thr Ile Glu Leu Asn Ser Thr Gly Ser Tyr Gly His Glu 930 935 940 Leu Asp Leu Gly Gln Gly Pro Asp Pro Ser Leu Asp Arg Glu Pro Glu 945 950 955 960 Leu Glu Met Glu Ser Leu Thr Gly Ser Pro Glu Asp Arg Ser Arg Gly 965 970 975 Glu His Ser Ser Thr Leu Pro Ala Ser Thr Pro Ser Tyr Thr Ser Gly 980 985 990 Thr Ser Pro Thr Ser Leu Ser Ser Leu Glu Glu Asp Ser Asp Ser Ser 995 1000 1005 Pro Ser Arg Arg Gln Arg Leu Glu Glu Ala Lys Gln Gln Arg Lys Ala 1010 1015 1020 Arg His Arg Ser His Gly Pro Leu Leu Pro Thr Ile Glu Asp Ser Ser 1025 1030 1035 1040 Glu Glu Glu Glu Leu Arg Glu Glu Glu Glu Leu Leu Arg Glu Gln Glu 1045 1050 1055 Lys Met Arg Glu Val Glu Gln Gln Arg Ile Arg Ser Thr Ala Arg Lys 1060 1065 1070 Thr Arg Arg Asp Lys Glu Glu Leu Arg Ala Gln Arg Arg Arg Glu Arg 1075 1080 1085 Ser Lys Thr Pro Pro Ser Asn Leu Ser Pro Ile Glu Asp Ala Ser Pro 1090 1095 1100 Thr Glu Glu Leu Arg Gln Ala Ala Glu Met Glu Glu Leu His Arg Ser 1105 1110 1115 1120 Ser Cys Ser Glu Tyr Ser Pro Ser Pro Ser Leu Asp Ser Glu Ala Glu 1125 1130 1135 Ala Leu Asp Gly Gly Pro Ser Arg Leu Tyr Lys Ser Gly Ser Glu Tyr 1140 1145 1150 Asn Leu Pro Thr Phe Met Ser Leu Tyr Ser Pro Thr Glu Thr Pro Ser 1155 1160 1165 Gly Ser Ser Thr Thr Pro Ser Ser Gly Arg Pro Leu Lys Ser Ala Glu 1170 1175 1180 Glu Ala Tyr Glu Glu Met Met Arg Lys Ala Glu Leu Leu Gln Arg Gln 1185 1190 1195 1200 Gln Gly Gln Ala Ala Gly Ala Arg Gly Pro His Gly Gly Pro Ser Gln 1205 1210 1215 Pro Thr Gly Pro Arg Gly Leu Gly Ser Phe Glu Tyr Gln Asp Thr Thr 1220 1225 1230 Asp Arg Glu Tyr Gly Gln Ala Ala Gln Pro Ala Ala Glu Gly Thr Pro 1235 1240 1245 Ala Ser Leu Gly Ala Ala Val Tyr Glu Glu Ile Leu Gln Thr Ser Gln 1250 1255 1260 Ser Ile Val Arg Met Arg Gln Ala Ser Ser Arg Asp Leu Ala Phe Ala 1265 1270 1275 1280 Glu Asp Lys Lys Lys Glu Lys Gln Phe Leu Asn Ala Glu Ser Ala Tyr 1285 1290 1295 Met Asp Pro Met Lys Gln Asn Gly Gly Pro Leu Thr Pro Gly Thr Ser 1300 1305 1310 Pro Thr Gln Leu Ala Ala Pro Val Ser Phe Ser Thr Pro Thr Ser Ser 1315 1320 1325 Asp Ser Ser Gly Gly Arg Val Ile Pro Asp Val Arg Val Thr Gln His 1330 1335 1340 Phe Ala Lys Glu Thr Gln Asp Pro Leu Lys Leu His Ser Ser Pro Ala 1345 1350 1355 1360 Ser Pro Ser Ser Ala Ser Lys Glu Ile Gly Met Pro Phe Ser Gln Gly 1365 1370 1375 Pro Gly Thr Pro Ala Thr Thr Ala Val Ala Pro Cys Pro Ala Gly Leu 1380 1385 1390 Pro Arg Gly Tyr Met Thr Pro Ala Ser Pro Ala Gly Ser Glu Arg Ser 1395 1400 1405 Pro Ser Pro Ser Ser Thr Ala His Ser Tyr Gly His Ser Pro Thr Thr 1410 1415 1420 Ala Asn Tyr Gly Ser Gln Thr Glu Asp Leu Pro Gln Ala Pro Ser Gly 1425 1430 1435 1440 Leu Ala Ala Ala Gly Arg Ala Ala Arg Glu Lys Pro Leu Ser Ala Ser 1445 1450 1455 Asp Gly Glu Gly Gly Thr Pro Gln Pro Ser Arg Ala Tyr Ser Tyr Phe 1460 1465 1470 Ala Ser Ser Ser Pro Pro Leu Ser Pro Ser Ser Pro Ser Glu Ser Pro 1475 1480 1485 Thr Phe Ser Pro Gly Lys Met Gly Pro Arg Ala Thr Ala Glu Phe Ser 1490 1495 1500 Thr Gln Thr Pro Ser Pro Ala Pro Ala Ser Asp Met Pro Arg Ser Pro 1505 1510 1515 1520 Gly Ala Pro Thr Pro Ser Pro Met Val Ala Gln Gly Thr Gln Thr Pro 1525 1530 1535 His Arg Pro Ser Thr Pro Arg Leu Val Trp Gln Glu Ser Ser Gln Glu 1540 1545 1550 Ala Pro Phe Met Val Ile Thr Leu Ala Ser Asp Ala Ser Ser Gln Thr 1555 1560 1565 Arg Met Val His Ala Ser Ala Ser Thr Ser Pro Leu Cys Ser Pro Thr 1570 1575 1580 Glu Thr Gln Pro Thr Thr His Gly Tyr Ser Gln Thr Thr Pro Pro Ser 1585 1590 1595 1600 Val Ser Gln Leu Pro Pro Glu Pro Pro Gly Pro Pro Gly Phe Pro Arg 1605 1610 1615 Val Pro Ser Ala Gly Ala Asp Gly Pro Leu Ala Leu Tyr Gly Trp Gly 1620 1625 1630 Ala Leu Pro Ala Glu Asn Ile Ser Leu Cys Arg Ile Ser Ser Val Pro 1635 1640 1645 Gly Thr Ser Arg Val Glu Pro Gly Pro Arg Thr Pro Gly Thr Ala Val 1650 1655 1660 Val Asp Leu Arg Thr Ala Val Lys Pro Thr Pro Ile Ile Leu Thr Asp 1665 1670 1675 1680 Gln Gly Met Asp Leu Thr Ser Leu Ala Val Glu Ala Arg Lys Tyr Gly 1685 1690 1695 Leu Ala Leu Asp Pro Ile Pro Gly Arg Gln Ser Thr Ala Val Gln Pro 1700 1705 1710 Leu Val Ile Asn Leu Asn Ala Gln Glu His Thr Phe Leu Ala Thr Ala 1715 1720 1725 Thr Thr Val Ser Ile Thr Met Ala Ser Ser Val Phe Met Ala Gln Gln 1730 1735 1740 Lys Gln Pro Val Val Tyr Gly Asp Pro Tyr Gln Ser Arg Leu Asp Phe 1745 1750 1755 1760 Gly Gln Gly Gly Gly Ser Pro Val Cys Leu Ala Gln Val Lys Gln Val 1765 1770 1775 Glu Gln Ala Val Gln Thr Ala Pro Tyr Arg Ser Gly Pro Arg Gly Arg 1780 1785 1790 Pro Arg Glu Ala Lys Phe Ala Arg Tyr Asn Leu Pro Asn Gln Val Ala 1795 1800 1805 Pro Leu Ala Arg Arg Asp Val Leu Ile Thr Gln Met Gly Thr Ala Gln 1810 1815 1820 Ser Ile Gly Leu Lys Pro Gly Pro Val Pro Glu Pro Gly Ala Glu Pro 1825 1830 1835 1840 His Arg Ala Thr Pro Ala Glu Leu Arg Ser His Ala Leu Pro Gly Ala 1845 1850 1855 Arg Lys Pro His Thr Val Val Val Gln Met Gly Glu Gly Thr Ala Gly 1860 1865 1870 Thr Val Thr Thr Leu Leu Pro Glu Glu Pro Ala Gly Ala Leu Asp Leu 1875 1880 1885 Thr Gly Met Arg Pro Glu Ser Gln Leu Ala Cys Cys Asp Met Val Tyr 1890 1895 1900 Lys Leu Pro Phe Gly Ser Ser Cys Thr Gly Thr Phe His Pro Ala Pro 1905 1910 1915 1920 Ser Val Pro Glu Lys Ser Met Ala Asp Ala Ala Pro Pro Gly Gln Ser 1925 1930 1935 Ser Ser Pro Phe Tyr Gly Pro Arg Asp Pro Glu Pro Pro Glu Pro Pro 1940 1945 1950 Thr Tyr Arg Ala Gln Gly Val Val Gly Pro Gly Pro His Glu Glu Gln 1955 1960 1965 Arg Pro Tyr Pro Gln Gly Leu Pro Gly Arg Leu Tyr Ser Ser Met Ser 1970 1975 1980 Asp Thr Asn Leu Ala Glu Ala Gly Leu Asn Tyr His Ala Gln Arg Ile 1985 1990 1995 2000 Gly Gln Leu Phe Gln Gly Pro Gly Arg Asp Ser Ala Met Asp Leu Ser 2005 2010 2015 Ser Leu Lys His Ser Tyr Ser Leu Gly Phe Ala Asp Gly Arg Tyr Leu 2020 2025 2030 Gly Gln Gly Leu Gln Tyr Gly Ser Val Thr Asp Leu Arg His Pro Thr 2035 2040 2045 Asp Leu Leu Ala His Pro Leu Pro Met Arg Arg Tyr Ser Ser Val Ser 2050 2055 2060 Asn Ile Tyr Ser Asp His Arg Tyr Gly Pro Arg Gly Asp Ala Val Gly 2065 2070 2075 2080 Phe Gln Glu Ala Ser Leu Ala Gln Tyr Ser Ala Thr Thr Ala Arg Glu 2085 2090 2095 Ile Ser Arg Met Cys Ala Ala Leu Asn Ser Met Asp Gln Tyr Gly Gly 2100 2105 2110 Arg His Gly Ser Gly Gly Gly Gly Pro Asp Leu Val Gln Tyr Gln Pro 2115 2120 2125 Gln His Gly Pro Gly Leu Ser Ala Pro Gln Ser Leu Val Pro Leu Arg 2130 2135 2140 Pro Gly Leu Leu Gly Asn Pro Thr Phe Pro Glu Gly His Pro Ser Pro 2145 2150 2155 2160 Gly Asn Leu Ala Gln Tyr Gly Pro Ala Ala Gly Gln Gly Thr Ala Val 2165 2170 2175 Arg Gln Leu Leu Pro Ser Thr Ala Thr Val Arg Ala Ala Asp Gly Met 2180 2185 2190 Ile Tyr Ser Thr Ile Asn Thr Pro Ile Ala Ala Thr Leu Pro Ile Thr 2195 2200 2205 Thr Gln Pro Ala Ser Val Leu Arg Pro Met Val Arg Gly Gly Met Tyr 2210 2215 2220 Arg Pro Tyr Ala Ser Gly Gly Ile Thr Ala Val Pro Leu Thr Ser Leu 2225 2230 2235 2240 Thr Arg Val Pro Met Ile Ala Pro Arg Val Pro Leu Gly Pro Thr Gly 2245 2250 2255 Leu Tyr Arg Tyr Pro Ala Pro Ser Arg Phe Pro Ile Ala Ser Ser Val 2260 2265 2270 Pro Pro Ala Glu Gly Pro Val Tyr Leu Gly Lys Pro Ala Ala Ala Lys 2275 2280 2285 Ala Pro Gly Ala Gly Gly Pro Ser Arg Pro Glu Met Pro Val Gly Ala 2290 2295 2300 Ala Arg Glu Glu Pro Leu Pro Thr Thr Thr Pro Ala Ala Ile Lys Glu 2305 2310 2315 2320 Ala Ala Gly Ala Pro Ala Pro Ala Pro Leu Ala Gly Gln Lys Pro Pro 2325 2330 2335 Ala Asp Ala Ala Pro Gly Gly Gly Ser Gly Ala Leu Ser Arg Pro Gly 2340 2345 2350 Phe Glu Lys Glu Glu Ala Ser Gln Glu Glu Arg Gln Arg Lys Gln Gln 2355 2360 2365 Glu Gln Leu Leu Gln Leu Glu Arg Glu Arg Val Glu Leu Glu Lys Leu 2370 2375 2380 Arg Gln Leu Arg Leu Gln Glu Glu Leu Glu Arg Glu Arg Val Glu Leu 2385 2390 2395 2400 Gln Arg His Arg Glu Glu Glu Gln Leu Leu Val Gln Arg Glu Leu Gln 2405 2410 2415 Glu Leu Gln Thr Ile Lys His His Val Leu Gln Gln Gln Gln Glu Glu 2420 2425 2430 Arg Gln Ala Gln Phe Ala Leu Gln Arg Glu Gln Leu Ala Gln Gln Arg 2435 2440 2445 Leu Gln Leu Glu Gln Ile Gln Gln Leu Gln Gln Gln Leu Gln Gln Gln 2450 2455 2460 Leu Glu Glu Gln Lys Gln Arg Gln Lys Ala Pro Phe Pro Ala Ala Cys 2465 2470 2475 2480 Glu Ala Pro Gly Arg Gly Pro Pro Leu Ala Ala Ala Glu Leu Ala Gln 2485 2490 2495 Asn Gly Gln Tyr Trp Pro Pro Leu Thr His Ala Ala Phe Ile Ala Met 2500 2505 2510 Ala Gly Pro Glu Gly Leu Gly Gln Pro Arg Glu Pro Val Leu His Arg 2515 2520 2525 Gly Leu Pro Ser Ser Ala Ser Asp Met Ser Leu Gln Thr Glu Glu Gln 2530 2535 2540 Trp Glu Ala Ser Arg Ser Gly Ile Lys Lys Arg His Ser Met Pro Arg 2545 2550 2555 2560 Leu Arg Asp Ala Cys Glu Leu Glu Ser Gly Thr Glu Pro Cys Val Val 2565 2570 2575 Arg Arg Ile Ala Asp Ser Ser Val Gln Thr Asp Asp Glu Asp Gly Glu 2580 2585 2590 Ser Arg Tyr Leu Leu Ser Arg Arg Arg Arg Ala Arg Arg Ser Ala Asp 2595 2600 2605 Cys Ser Val Gln Thr Asp Asp Glu Asp Ser Ala Glu Trp Glu Gln Pro 2610 2615 2620 Val Arg Arg Arg Arg Ser Arg Leu Pro Arg His Ser Asp Ser Gly Ser 2625 2630 2635 2640 Asp Ser Lys His Asp Ala Thr Ala Ser Ser Ser Ser Ala Ala Ala Thr 2645 2650 2655 Val Arg Ala Met Ser Ser Val Gly Ile Gln Thr Ile Ser Asp Cys Ser 2660 2665 2670 Val Gln Thr Glu Pro Asp Gln Leu Pro Arg Val Ser Pro Ala Ile His 2675 2680 2685 Ile Thr Ala Ala Thr Asp Pro Lys Val Glu Ile Val Arg Tyr Ile Ser 2690 2695 2700 Ala Pro Glu Lys Thr Gly Arg Gly Glu Ser Leu Ala Cys Gln Thr Glu 2705 2710 2715 2720 Pro Asp Gly Gln Ala Gln Gly Val Ala Gly Pro Gln Leu Val Gly Pro 2725 2730 2735 Thr Ala Ile Ser Pro Tyr Leu Pro Gly Ile Gln Ile Val Thr Pro Gly 2740 2745 2750 Pro Leu Gly Arg Phe Glu Lys Lys Lys Pro Asp Pro Leu Glu Ile Gly 2755 2760 2765 Tyr Gln Ala His Leu Pro Pro Glu Ser Leu Ser Gln Leu Val Ser Arg 2770 2775 2780 Gln Pro Pro Lys Ser Pro Gln Val Leu Tyr Ser Pro Val Ser Pro Leu 2785 2790 2795 2800 Ser Pro His Arg Leu Leu Asp Thr Ser Phe Ala Ser Ser Glu Arg Leu 2805 2810 2815 Asn Lys Ala His Val Ser Pro Gln Lys His Phe Thr Ala Asp Ser Ala 2820 2825 2830 Leu Arg Gln Gln Thr Leu Pro Arg Pro Met Lys Thr Leu Gln Arg Ser 2835 2840 2845 Leu Ser Asp Pro Lys Pro Leu Ser Pro Thr Ala Glu Glu Ser Ala Lys 2850 2855 2860 Glu Arg Phe Ser Leu Tyr Gln His Gln Gly Gly Leu Gly Ser Gln Val 2865 2870 2875 2880 Ser Ala Leu Pro Pro Asn Ser Leu Val Arg Lys Val Lys Arg Thr Leu 2885 2890 2895 Pro Ser Pro Pro Pro Glu Glu Ala His Leu Pro Leu Ala Gly Gln Ala 2900 2905 2910 Ser Pro Gln Leu Tyr Ala Ala Ser Leu Leu Gln Arg Gly Leu Thr Gly 2915 2920 2925 Pro Thr Thr Val Pro Ala Thr Lys Ala Ser Leu Leu Arg Glu Leu Asp 2930 2935 2940 Arg Asp Leu Arg Leu Val Glu His Glu Ser Thr Lys Leu Arg Lys Lys 2945 2950 2955 2960 Gln Ala Glu Leu Asp Glu Glu Glu Lys Glu Ile Asp Ala Lys Leu Lys 2965 2970 2975 Tyr Leu Glu Leu Gly Ile Thr Gln Arg Lys Glu Ser Leu Ala Lys Asp 2980 2985 2990 Arg Gly Gly Arg Asp Tyr Pro Pro Leu Arg Gly Leu Gly Glu His Arg 2995 3000 3005 Asp Tyr Leu Ser Asp Ser Glu Leu Asn Gln Leu Arg Leu Gln Gly Cys 3010 3015 3020 Thr Thr Pro Ala Gly Gln Phe Val Asp Phe Pro Ala Thr Ala Ala Ala 3025 3030 3035 3040 Pro Ala Thr Pro Ser Gly Pro Thr Ala Phe Gln Gln Pro Arg Phe Gln 3045 3050 3055 Pro Pro Ala Pro Gln Tyr Ser Ala Gly Ser Gly Gly Pro Thr Gln Asn 3060 3065 3070 Gly Phe Pro Ala His Gln Ala Pro Thr Tyr Pro Gly Pro Ser Thr Tyr 3075 3080 3085 Pro Ala Pro Ala Phe Pro Pro Gly Ala Ser Tyr Pro Ala Glu Pro Gly 3090 3095 3100 Leu Pro Asn Gln Gln Ala Phe Arg Pro Thr Gly His Tyr Ala Gly Gln 3105 3110 3115 3120 Thr Pro Met Pro Thr Thr Gln Ser Thr Leu Phe Pro Val Pro Ala Asp 3125 3130 3135 Ser Arg Ala Pro Leu Gln Lys Pro Arg Gln Thr Ser Leu Ala Asp Leu 3140 3145 3150 Glu Gln Lys Val Pro Thr Asn Tyr Glu Val Ile Ala Ser Pro Val Val 3155 3160 3165 Pro Met Ser Ser Ala Pro Ser Glu Thr Ser Tyr Ser Gly Pro Ala Val 3170 3175 3180 Ser Ser Gly Tyr Glu Gln Gly Lys Val Pro Glu Val Pro Arg Ala Gly 3185 3190 3195 3200 Asp Arg Gly Ser Val Ser Gln Ser Pro Ala Pro Thr Tyr Pro Ser Asp 3205 3210 3215 Ser His Tyr Thr Ser Leu Glu Gln Asn Val Pro Arg Asn Tyr Val Met 3220 3225 3230 Ile Asp Asp Ile Ser Glu Leu Thr Lys Asp Ser Thr Ser Thr Ala Pro 3235 3240 3245 Asp Ser Gln Arg Leu Glu Pro Leu Gly Pro Gly Ser Ser Gly Arg Pro 3250 3255 3260 Gly Lys Glu Pro Gly Glu Pro Gly Val Leu Asp Gly Pro Thr Leu Pro 3265 3270 3275 3280 Cys Cys Tyr Ala Arg Gly Glu Glu Glu Ser Glu Glu Asp Ser Tyr Asp 3285 3290 3295 Pro Arg Gly Lys Gly Gly His Leu Arg Ser Met Glu Ser Asn Gly Arg 3300 3305 3310 Pro Ala Ser Thr His Tyr Tyr Gly Asp Ser Asp Tyr Arg His Gly Ala 3315 3320 3325 Arg Val Glu Lys Tyr Gly Pro Gly Pro Met Gly Pro Lys His Pro Ser 3330 3335 3340 Lys Ser Leu Ala Pro Ala Ala Ile Ser Ser Lys Arg Ser Lys His Arg 3345 3350 3355 3360 Lys Gln Gly Met Glu Gln Lys Ile Ser Lys Phe Ser Pro Ile Glu Glu 3365 3370 3375 Ala Lys Asp Val Glu Ser Asp Leu Ala Ser Tyr Pro Pro Pro Ala Val 3380 3385 3390 Ser Ser Ser Leu Val Ser Arg Gly Arg Lys Phe Gln Asp Glu Ile Thr 3395 3400 3405 Tyr Gly Leu Lys Lys Asn Val Tyr Glu Gln Gln Lys Tyr Tyr Gly Met 3410 3415 3420 Ser Ser Arg Asp Ala Val Glu Asp Asp Arg Ile Tyr Gly Gly Ser Ser 3425 3430 3435 3440 Arg Ser Arg Ala Pro Ser Ala Tyr Ser Gly Glu Lys Leu Ser Ser His 3445 3450 3455 Asp Phe Ser Gly Trp Gly Lys Gly Tyr Glu Arg Glu Arg Glu Ala Val 3460 3465 3470 Glu Arg Leu Gln Lys Ala Gly Pro Lys Pro Ser Ser Leu Ser Met Ala 3475 3480 3485 His Ser Arg Val Arg Pro Pro Met Arg Ser Gln Ala Ser Glu Glu Glu 3490 3495 3500 Ser Pro Val Ser Pro Leu Gly Arg Pro Arg Pro Ala Gly Gly Pro Leu 3505 3510 3515 3520 Pro Pro Gly Gly Asp Thr Cys Pro Gln Phe Cys Ser Ser His Ser Met 3525 3530 3535 Pro Asp Val Gln Glu His Val Lys Asp Gly Pro Arg Ala His Ala Tyr 3540 3545 3550 Lys Arg Glu Glu Gly Tyr Ile Leu Asp Asp Ser His Cys Val Val Ser 3555 3560 3565 Asp Ser Glu Ala Tyr His Leu Gly Gln Glu Glu Thr Asp Trp Phe Asp 3570 3575 3580 Lys Pro Arg Asp Ala Arg Ser Asp Arg Phe Arg His His Gly Gly His 3585 3590 3595 3600 Ala Val Ser Ser Ser Ser Gln Lys Arg Gly Pro Ala Arg His Ser Tyr 3605 3610 3615 His Asp Tyr Asp Glu Pro Pro Glu Glu Gly Leu Trp Pro His Asp Glu 3620 3625 3630 Gly Gly Pro Gly Arg His Ala Ser Ala Lys Glu His Arg His Gly Asp 3635 3640 3645 His Gly Arg His Ser Gly Arg His Thr Gly Glu Glu Pro Gly Arg Arg 3650 3655 3660 Ala Ala Lys Pro His Ala Arg Asp Leu Gly Arg His Glu Ala Arg Pro 3665 3670 3675 3680 His Ser Gln Pro Ser Ser Ala Pro Ala Met Pro Lys Lys Gly Gln Pro 3685 3690 3695 Gly Tyr Pro Ser Ser Ala Glu Tyr Ser Gln Pro Ser Arg Ala Ser Ser 3700 3705 3710 Ala Tyr His His Ala Ser Asp Ser Lys Lys Gly Ser Arg Gln Ala His 3715 3720 3725 Ser Gly Pro Ala Ala Leu Gln Ser Lys Ala Glu Pro Gln Ala Gln Pro 3730 3735 3740 Gln Leu Gln Gly Arg Gln Ala Ala Pro Gly Pro Gln Gln Ser Gln Ser 3745 3750 3755 3760 Pro Ser Ser Arg Gln Ile Pro Ser Gly Ala Ala Ser Arg Gln Pro Gln 3765 3770 3775 Thr Gln Gln Gln Gln Gln Gly Leu Gly Leu Gln Pro Pro Gln Gln Ala 3780 3785 3790 Leu Thr Gln Ala Arg Leu Gln Gln Gln Ser Gln Pro Thr Thr Arg Gly 3795 3800 3805 Ser Ala Pro Ala Ala Ser Gln Pro Ala Gly Lys Pro Gln Pro Gly Pro 3810 3815 3820 Ser Thr Ala Thr Gly Pro Gln Pro Ala Gly Pro Pro Arg Ala Glu Gln 3825 3830 3835 3840 Thr Asn Gly Ser Lys Gly Thr Ala Lys Ala Pro Gln Gln Gly Arg Ala 3845 3850 3855 Pro Gln Ala Gln Pro Thr Pro Gly Pro Gly Pro Ala Gly Val Lys Ala 3860 3865 3870 Gly Ala Arg Pro Gly Gly Thr Pro Gly Ala Pro Ala Gly Gln Pro Gly 3875 3880 3885 Ala Asp Gly Glu Ser Val Phe Ser Lys Ile Leu Pro Gly Gly Ala Ala 3890 3895 3900 Glu Gln Ala Gly Lys Leu Thr Glu Ala Val Ser Ala Phe Gly Lys Lys 3905 3910 3915 3920 Phe Ser Ser Phe Trp 3925 <210> 101 <211> 350 <212> PRT <213> Homo sapiens <400> 101 Met Pro Gly His Leu Pro Ser Glu Asp Ser His Tyr Gly Met Glu Met 1 5 10 15 Leu Thr Ala Lys Ala Ile Gly Ile Ser Glu Pro Ile Lys Val Leu Tyr 20 25 30 Ser Lys Phe Leu Met His Pro Glu Glu Leu Phe Val Val Gly Leu Pro 35 40 45 Glu Gly Ile Ser Leu Arg Arg Pro Asn Cys Phe Gly Ile Ala Lys Leu 50 55 60 Trp Lys Ile Leu Glu Ala Ser Asn Ser Ile Gln Phe Val Ile Lys Ser 65 70 75 80 Pro Leu Leu Ala Ser Met Ile Phe Pro Val Ser Ser Ala His His Lys 85 90 95 Pro Gln Pro Pro Asn Arg Leu Ala Leu Thr Gly Gln Val Val Leu Lys 100 105 110 Met Glu Thr Leu Glu Ala Val Arg Pro Lys Leu Leu Thr Glu Gly Val 115 120 125 Lys Glu Pro Ile Val Asp Ser Gln Gly Thr Gln His Gly Val Ala Gly 130 135 140 His Gly Thr Ala Ser Ser Leu Gly Phe Ser Pro Pro Ala Leu Pro Pro 145 150 155 160 Glu Arg Asp Ser Arg Asp Pro Leu Val Gly Glu Ser Leu Lys Arg Gln 165 170 175 Gly Phe Gln Glu Asn Tyr Asp Ala Arg Leu Leu Arg Ile Asp Ile Ala 180 185 190 Asn Thr Leu Arg Glu Gln Val Gln Glu Leu Phe Asn Lys Thr Tyr Gly 195 200 205 Glu Ala Leu Gly Ile Lys Tyr Pro Val Gln Val Pro Tyr Lys Trp Ile 210 215 220 Lys Ser Asn Pro Gly Ser Met Ile Ile Glu Glu Leu Pro Pro Gly Ile 225 230 235 240 Leu Phe Arg Lys Pro Phe Gly Ser Gln Asn Leu Glu Arg Ile Leu Ala 245 250 255 Met Ala Asn Lys Ile Thr Phe Thr Val Thr Arg Pro Phe Gln Gly Leu 260 265 270 Ile Arg Lys Pro Asp Glu Asp Asp Thr Asn Arg Leu Gly Glu Val Ile 275 280 285 Leu Gln Glu Gln Val Lys Glu Leu Phe Asn Glu Lys Tyr Ser Gln Cys 290 295 300 Leu Trp Leu Leu Gln Gln Gln Gln His His Ile Ser Glu Gly Arg Pro 305 310 315 320 Phe Ala Glu Ile Cys Asn Asp Ala Lys Val Pro Gly Tyr Thr Glu Pro 325 330 335 Phe Thr Arg His Leu Gly Ala Thr Trp His Asp Gly Ser Asp 340 345 350 <210> 102 <211> 1241 <212> PRT <213> Homo sapiens <400> 102 Met Ala His Leu Glu Leu Leu Leu Val Glu Asn Phe Lys Ser Trp Arg 1 5 10 15 Gly Arg Gln Val Ile Gly Pro Phe Arg Arg Phe Thr Cys Ile Ile Gly 20 25 30 Pro Asn Gly Ser Gly Lys Ser Asn Val Met Asp Ala Leu Ser Phe Val 35 40 45 Met Gly Glu Lys Ile Ala Asn Leu Arg Val Lys Asn Ile Gln Glu Leu 50 55 60 Ile His Gly Ala His Ile Gly Lys Pro Ile Ser Ser Ser Ala Ser Val 65 70 75 80 Lys Ile Ile Tyr Val Glu Glu Ser Gly Glu Glu Lys Thr Phe Ala Arg 85 90 95 Ile Ile Arg Gly Gly Cys Ser Glu Phe Arg Phe Asn Asp Asn Leu Val 100 105 110 Ser Arg Ser Val Tyr Ile Ala Glu Leu Glu Lys Ile Gly Ile Ile Val 115 120 125 Lys Ala Gln Asn Cys Leu Val Phe Gln Gly Thr Val Glu Ser Ile Ser 130 135 140 Val Lys Lys Pro Lys Glu Arg Thr Gln Phe Phe Glu Glu Ile Ser Thr 145 150 155 160 Ser Gly Glu Leu Ile Gly Glu Tyr Glu Glu Lys Lys Arg Lys Leu Gln 165 170 175 Lys Ala Glu Glu Asp Ala Gln Phe Asn Phe Asn Lys Lys Lys Asn Ile 180 185 190 Ala Ala Glu Arg Arg Gln Ala Lys Leu Glu Lys Glu Glu Ala Glu Arg 195 200 205 Tyr Gln Ser Leu Leu Glu Glu Leu Lys Met Asn Lys Ile Gln Leu Gln 210 215 220 Leu Phe Gln Leu Tyr His Asn Glu Lys Lys Ile His Leu Leu Asn Thr 225 230 235 240 Lys Leu Glu His Val Asn Arg Asp Leu Ser Val Lys Arg Glu Ser Leu 245 250 255 Ser His His Glu Asn Ile Val Lys Ala Arg Lys Lys Glu His Gly Met 260 265 270 Leu Thr Arg Gln Leu Gln Gln Thr Glu Lys Glu Leu Lys Ser Val Glu 275 280 285 Thr Leu Leu Asn Gln Lys Arg Pro Gln Tyr Ile Lys Ala Lys Glu Asn 290 295 300 Thr Ser His His Leu Lys Lys Leu Asp Val Ala Lys Lys Ser Ile Lys 305 310 315 320 Asp Ser Glu Lys Gln Cys Ser Lys Gln Glu Asp Asp Ile Lys Ala Leu 325 330 335 Glu Thr Glu Leu Ala Asp Leu Asp Ala Ala Trp Arg Ser Phe Glu Lys 340 345 350 Gln Ile Glu Glu Glu Ile Leu His Lys Lys Arg Asp Ile Glu Leu Glu 355 360 365 Ala Ser Gln Leu Asp Arg Tyr Lys Glu Leu Lys Glu Gln Val Arg Lys 370 375 380 Lys Val Ala Thr Met Thr Gln Gln Leu Glu Lys Leu Gln Trp Glu Gln 385 390 395 400 Lys Thr Asp Glu Glu Arg Leu Ala Phe Glu Lys Arg Arg His Gly Glu 405 410 415 Val Gln Gly Asn Leu Lys Gln Ile Lys Glu Gln Ile Glu Asp His Lys 420 425 430 Lys Arg Ile Glu Lys Leu Glu Glu Tyr Thr Lys Thr Cys Met Asp Cys 435 440 445 Leu Lys Glu Lys Lys Gln Gln Glu Glu Thr Leu Val Asp Glu Ile Glu 450 455 460 Lys Thr Lys Ser Arg Met Ser Glu Phe Asn Glu Glu Leu Asn Leu Ile 465 470 475 480 Arg Ser Glu Leu Gln Asn Ala Gly Ile Asp Thr His Glu Gly Lys Arg 485 490 495 Gln Gln Lys Arg Ala Glu Val Leu Glu His Leu Lys Arg Leu Tyr Pro 500 505 510 Asp Ser Val Phe Gly Arg Leu Phe Asp Leu Cys His Pro Ile His Lys 515 520 525 Lys Tyr Gln Leu Ala Val Thr Lys Val Phe Gly Arg Phe Ile Thr Ala 530 535 540 Ile Val Val Ala Ser Glu Lys Val Ala Lys Asp Cys Ile Arg Phe Leu 545 550 555 560 Lys Glu Glu Arg Ala Glu Pro Glu Thr Phe Leu Ala Leu Asp Tyr Leu 565 570 575 Asp Ile Lys Pro Ile Asn Glu Arg Leu Arg Glu Leu Lys Gly Cys Lys 580 585 590 Met Val Ile Asp Val Ile Lys Thr Gln Phe Pro Gln Leu Lys Lys Val 595 600 605 Ile Gln Phe Val Cys Gly Asn Gly Leu Val Cys Glu Thr Met Glu Glu 610 615 620 Ala Arg His Ile Ala Leu Ser Gly Pro Glu Arg Gln Lys Thr Val Ala 625 630 635 640 Leu Asp Gly Thr Leu Phe Leu Lys Ser Gly Val Ile Ser Gly Gly Ser 645 650 655 Ser Asp Leu Lys Tyr Lys Ala Arg Cys Trp Asp Glu Lys Glu Leu Lys 660 665 670 Asn Leu Arg Asp Arg Arg Ser Gln Lys Ile Gln Glu Leu Lys Gly Leu 675 680 685 Met Lys Thr Leu Arg Lys Glu Thr Asp Leu Lys Gln Ile Gln Thr Leu 690 695 700 Ile Gln Gly Thr Gln Thr Arg Leu Lys Tyr Ser Gln Asn Glu Leu Glu 705 710 715 720 Met Ile Lys Lys Lys His Leu Val Ala Phe Tyr Gln Glu Gln Ser Gln 725 730 735 Leu Gln Ser Glu Leu Leu Asn Ile Glu Ser Gln Cys Ile Met Leu Ser 740 745 750 Glu Gly Ile Lys Glu Arg Gln Arg Arg Ile Lys Glu Phe Gln Glu Lys 755 760 765 Ile Asp Lys Val Glu Asp Asp Ile Phe Gln His Phe Cys Glu Glu Ile 770 775 780 Gly Val Glu Asn Ile Arg Glu Phe Glu Asn Lys His Val Lys Arg Gln 785 790 795 800 Gln Glu Ile Asp Gln Lys Arg Tyr Phe Tyr Lys Lys Ile Leu Glu Phe 805 810 815 Glu Lys Gln Lys Thr Arg Leu Asn Val Gln Leu Glu Tyr Ser Arg Ser 820 825 830 His Leu Lys Lys Lys Leu Asn Lys Ile Asn Thr Leu Lys Glu Thr Ile 835 840 845 Gln Lys Gly Ser Glu Asp Ile Asp His Leu Lys Lys Ala Glu Glu Asn 850 855 860 Cys Leu Gln Thr Val Asn Glu Leu Met Ala Lys Gln Gln Gln Leu Lys 865 870 875 880 Asp Ile Arg Val Thr Gln Asn Ser Ser Ala Glu Lys Val Gln Thr Gln 885 890 895 Ile Glu Glu Glu Arg Lys Lys Phe Leu Ala Val Asp Arg Glu Val Gly 900 905 910 Lys Leu Gln Lys Glu Val Val Ser Ile Gln Thr Ser Leu Glu Gln Lys 915 920 925 Arg Leu Glu Lys His Asn Leu Leu Leu Asp Cys Lys Val Gln Asp Ile 930 935 940 Glu Ile Ile Leu Leu Ser Gly Ser Leu Asp Asp Ile Ile Glu Val Glu 945 950 955 960 Met Gly Thr Glu Ala Glu Ser Thr Gln Ala Thr Ile Asp Ile Tyr Glu 965 970 975 Lys Glu Glu Ala Phe Glu Ile Asp Tyr Ser Ser Leu Lys Glu Asp Leu 980 985 990 Lys Ala Leu Gln Ser Asp Gln Glu Ile Glu Ala His Leu Arg Leu Leu 995 1000 1005 Leu Gln Gln Val Ala Ser Gln Glu Asp Ile Leu Leu Lys Thr Ala Ala 1010 1015 1020 Pro Asn Leu Arg Ala Leu Glu Asn Leu Lys Thr Val Arg Asp Lys Phe 1025 1030 1035 1040 Gln Glu Ser Thr Asp Ala Phe Glu Ala Ser Arg Lys Glu Ala Arg Leu 1045 1050 1055 Cys Arg Gln Glu Phe Glu Gln Val Lys Lys Arg Arg Tyr Asp Leu Phe 1060 1065 1070 Thr Gln Cys Phe Glu His Val Ser Ile Ser Ile Asp Gln Ile Tyr Lys 1075 1080 1085 Lys Leu Cys Arg Asn Asn Ser Ala Gln Ala Phe Leu Ser Pro Glu Asn 1090 1095 1100 Pro Glu Glu Pro Tyr Leu Glu Gly Ile Ser Tyr Asn Cys Val Ala Pro 1105 1110 1115 1120 Gly Lys Arg Phe Met Pro Met Asp Asn Leu Ser Gly Gly Glu Lys Cys 1125 1130 1135 Val Ala Ala Leu Ala Leu Leu Phe Ala Val His Ser Phe Arg Pro Ala 1140 1145 1150 Pro Phe Phe Val Leu Asp Glu Val Asp Ala Ala Leu Asp Asn Thr Asn 1155 1160 1165 Ile Gly Lys Val Ser Ser Tyr Ile Lys Glu Gln Thr Gln Asp Gln Phe 1170 1175 1180 Gln Met Ile Val Ile Ser Leu Lys Glu Glu Phe Tyr Ser Arg Ala Asp 1185 1190 1195 1200 Ala Leu Ile Gly Ile Tyr Pro Glu Tyr Asp Asp Cys Met Phe Ser Arg 1205 1210 1215 Val Leu Thr Leu Asp Leu Ser Gln Tyr Pro Asp Thr Glu Gly Gln Glu 1220 1225 1230 Ser Ser Lys Arg His Gly Glu Ser Arg 1235 1240 <210> 103 <211> 2210 <212> PRT <213> Homo sapiens <400> 103 Met Thr Ala Ala Ala Asn Trp Val Ala Asn Gly Ala Ser Leu Glu Asp 1 5 10 15 Cys His Ser Asn Leu Phe Ser Leu Ala Glu Leu Thr Gly Ile Lys Trp 20 25 30 Arg Arg Tyr Asn Phe Gly Gly His Gly Asp Cys Gly Pro Ile Ile Ser 35 40 45 Ala Pro Ala Gln Asp Asp Pro Ile Leu Leu Ser Phe Ile Arg Cys Leu 50 55 60 Gln Ala Asn Leu Leu Cys Val Trp Arg Arg Asp Val Lys Pro Asp Cys 65 70 75 80 Lys Glu Leu Trp Ile Phe Trp Trp Gly Asp Glu Pro Asn Leu Val Gly 85 90 95 Val Ile His His Glu Leu Gln Val Val Glu Glu Gly Leu Trp Glu Asn 100 105 110 Gly Leu Ser Tyr Glu Cys Arg Thr Leu Leu Phe Lys Ala Ile His Asn 115 120 125 Leu Leu Glu Arg Cys Leu Met Asp Lys Asn Phe Val Arg Ile Gly Lys 130 135 140 Trp Phe Val Arg Pro Tyr Glu Lys Asp Glu Lys Pro Val Asn Lys Ser 145 150 155 160 Glu His Leu Ser Cys Ala Phe Thr Phe Phe Leu His Gly Glu Ser Asn 165 170 175 Val Cys Thr Ser Val Glu Ile Ala Gln His Gln Pro Ile Tyr Leu Ile 180 185 190 Asn Glu Glu His Ile His Met Ala Gln Ser Ser Pro Ala Pro Phe Gln 195 200 205 Val Leu Val Ser Pro Tyr Gly Leu Asn Gly Thr Leu Thr Gly Gln Ala 210 215 220 Tyr Lys Met Ser Asp Pro Ala Thr Arg Lys Leu Ile Glu Glu Trp Gln 225 230 235 240 Tyr Phe Tyr Pro Met Val Leu Lys Lys Lys Glu Glu Ser Lys Glu Glu 245 250 255 Asp Glu Leu Gly Tyr Asp Asp Asp Phe Pro Val Ala Val Glu Val Ile 260 265 270 Val Gly Gly Val Arg Met Val Tyr Pro Ser Ala Phe Val Leu Ile Ser 275 280 285 Gln Asn Asp Ile Pro Val Pro Gln Ser Val Ala Ser Ala Gly Gly His 290 295 300 Ile Ala Val Gly Gln Gln Gly Leu Gly Ser Val Lys Asp Pro Ser Asn 305 310 315 320 Cys Gly Met Pro Leu Thr Pro Pro Thr Ser Pro Glu Gln Ala Ile Leu 325 330 335 Gly Glu Ser Gly Gly Met Gln Ser Ala Ala Ser His Leu Val Ser Gln 340 345 350 Asp Gly Gly Met Ile Thr Met His Ser Pro Lys Arg Ser Gly Lys Ile 355 360 365 Pro Pro Lys Leu His Asn His Met Val His Arg Val Trp Lys Glu Cys 370 375 380 Ile Leu Asn Arg Thr Gln Ser Lys Arg Ser Gln Met Ser Thr Pro Thr 385 390 395 400 Leu Glu Glu Glu Pro Ala Ser Asn Pro Ala Thr Trp Asp Phe Val Asp 405 410 415 Pro Thr Gln Arg Val Ser Cys Ser Cys Ser Arg His Lys Leu Leu Lys 420 425 430 Arg Cys Ala Val Gly Pro Asn Arg Pro Pro Thr Val Ser Gln Pro Gly 435 440 445 Phe Ser Ala Gly Pro Ser Ser Ser Ser Ser Leu Pro Pro Pro Ala Ser 450 455 460 Ser Lys His Lys Thr Ala Glu Arg Gln Glu Lys Gly Asp Lys Leu Gln 465 470 475 480 Lys Arg Pro Leu Ile Pro Phe His His Arg Pro Ser Val Ala Glu Glu 485 490 495 Leu Cys Met Glu Gln Asp Thr Pro Gly Gln Lys Leu Gly Leu Ala Gly 500 505 510 Ile Asp Ser Ser Leu Glu Val Ser Ser Ser Arg Lys Tyr Asp Lys Gln 515 520 525 Met Ala Val Pro Ser Arg Asn Thr Ser Lys Gln Met Asn Leu Asn Pro 530 535 540 Met Asp Ser Pro His Ser Pro Ile Ser Pro Leu Pro Pro Thr Leu Ser 545 550 555 560 Pro Gln Pro Arg Gly Gln Glu Thr Glu Ser Leu Asp Pro Pro Ser Val 565 570 575 Pro Val Asn Pro Ala Leu Tyr Gly Asn Gly Leu Glu Leu Gln Gln Leu 580 585 590 Ser Thr Leu Asp Asp Arg Thr Val Leu Val Gly Gln Arg Leu Pro Leu 595 600 605 Met Ala Glu Val Ser Glu Thr Ala Leu Tyr Cys Gly Ile Arg Pro Ser 610 615 620 Asn Pro Glu Ser Ser Glu Lys Trp Trp His Ser Tyr Arg Leu Pro Pro 625 630 635 640 Ser Asp Asp Ala Glu Phe Arg Pro Pro Glu Leu Gln Gly Glu Arg Cys 645 650 655 Asp Ala Lys Met Glu Val Asn Ser Glu Ser Thr Ala Leu Gln Arg Leu 660 665 670 Leu Ala Gln Pro Asn Lys Arg Phe Lys Ile Trp Gln Asp Lys Gln Pro 675 680 685 Gln Leu Gln Pro Leu His Phe Leu Asp Pro Leu Pro Leu Ser Gln Gln 690 695 700 Pro Gly Asp Ser Leu Gly Glu Val Asn Asp Pro Tyr Thr Phe Glu Asp 705 710 715 720 Gly Asp Ile Lys Tyr Ile Phe Thr Ala Asn Lys Lys Cys Lys Gln Gly 725 730 735 Thr Glu Lys Asp Ser Leu Lys Lys Asn Lys Ser Glu Asp Gly Phe Gly 740 745 750 Thr Lys Asp Val Thr Thr Pro Gly His Ser Thr Pro Val Pro Asp Gly 755 760 765 Lys Asn Ala Met Ser Ile Phe Ser Ser Ala Thr Lys Thr Asp Val Arg 770 775 780 Gln Asp Asn Ala Ala Gly Arg Ala Gly Ser Ser Ser Leu Thr Gln Val 785 790 795 800 Thr Asp Leu Ala Pro Ser Leu His Asp Leu Asp Asn Ile Phe Asp Asn 805 810 815 Ser Asp Asp Asp Glu Leu Gly Ala Val Ser Pro Ala Leu Arg Ser Ser 820 825 830 Lys Met Pro Ala Val Gly Thr Glu Asp Arg Pro Leu Gly Lys Asp Gly 835 840 845 Arg Ala Ala Val Pro Tyr Pro Pro Thr Val Ala Asp Leu Gln Arg Met 850 855 860 Phe Pro Thr Pro Pro Ser Leu Glu Gln His Pro Ala Phe Ser Pro Val 865 870 875 880 Met Asn Tyr Lys Asp Gly Ile Ser Ser Glu Thr Val Thr Ala Leu Gly 885 890 895 Met Met Glu Ser Pro Met Val Ser Met Val Ser Thr Gln Leu Thr Glu 900 905 910 Phe Lys Met Glu Val Glu Asp Gly Leu Gly Ser Pro Lys Pro Glu Glu 915 920 925 Ile Lys Asp Phe Ser Tyr Val His Lys Val Pro Ser Phe Gln Pro Phe 930 935 940 Val Gly Ser Ser Met Phe Ala Pro Leu Lys Met Leu Pro Ser His Cys 945 950 955 960 Leu Leu Pro Leu Lys Ile Pro Asp Ala Cys Leu Phe Arg Pro Ser Trp 965 970 975 Ala Ile Pro Pro Lys Ile Glu Gln Leu Pro Met Pro Pro Ala Ala Thr 980 985 990 Phe Ile Arg Asp Gly Tyr Asn Asn Val Pro Ser Val Gly Ser Leu Ala 995 1000 1005 Asp Pro Asp Tyr Leu Asn Thr Pro Gln Met Asn Thr Pro Val Thr Leu 1010 1015 1020 Asn Ser Ala Ala Pro Ala Ser Asn Ser Gly Ala Gly Val Leu Pro Ser 1025 1030 1035 1040 Pro Ala Thr Pro Arg Phe Ser Val Pro Thr Pro Arg Thr Pro Arg Thr 1045 1050 1055 Pro Arg Thr Pro Arg Gly Gly Gly Thr Ala Ser Gly Gln Gly Ser Val 1060 1065 1070 Lys Tyr Asp Ser Thr Asp Gln Gly Ser Pro Ala Ser Thr Pro Ser Thr 1075 1080 1085 Thr Arg Pro Leu Asn Ser Val Glu Pro Ala Thr Met Gln Pro Ile Pro 1090 1095 1100 Glu Ala His Ser Leu Tyr Val Thr Leu Ile Leu Ser Asp Ser Val Met 1105 1110 1115 1120 Asn Ile Phe Lys Asp Arg Asn Phe Asp Ser Cys Cys Ile Cys Ala Cys 1125 1130 1135 Asn Met Asn Ile Lys Gly Ala Asp Val Gly Leu Tyr Ile Pro Asp Ser 1140 1145 1150 Ser Asn Glu Asp Gln Tyr Arg Cys Thr Cys Gly Phe Ser Ala Ile Met 1155 1160 1165 Asn Arg Lys Leu Gly Tyr Asn Ser Gly Leu Phe Leu Glu Asp Glu Leu 1170 1175 1180 Asp Ile Phe Gly Lys Asn Ser Asp Ile Gly Gln Ala Ala Glu Arg Arg 1185 1190 1195 1200 Leu Met Met Cys Gln Ser Thr Phe Leu Pro Gln Val Glu Gly Thr Lys 1205 1210 1215 Lys Pro Gln Glu Pro Pro Ile Ser Leu Leu Leu Leu Leu Gln Asn Gln 1220 1225 1230 His Thr Gln Pro Phe Ala Ser Leu Asn Phe Leu Asp Tyr Ile Ser Ser 1235 1240 1245 Asn Asn Arg Gln Thr Leu Pro Cys Val Ser Trp Ser Tyr Asp Arg Val 1250 1255 1260 Gln Ala Asp Asn Asn Asp Tyr Trp Thr Glu Cys Phe Asn Ala Leu Glu 1265 1270 1275 1280 Gln Gly Arg Gln Tyr Val Asp Asn Pro Thr Gly Gly Lys Val Asp Glu 1285 1290 1295 Ala Leu Val Arg Ser Ala Thr Val His Ser Trp Pro His Ser Asn Val 1300 1305 1310 Leu Asp Ile Ser Met Leu Ser Ser Gln Asp Val Val Arg Met Leu Leu 1315 1320 1325 Ser Leu Gln Pro Phe Leu Gln Asp Ala Ile Gln Lys Lys Arg Thr Gly 1330 1335 1340 Arg Thr Trp Glu Asn Ile Gln His Val Gln Gly Pro Leu Thr Trp Gln 1345 1350 1355 1360 Gln Phe His Lys Met Ala Gly Arg Gly Thr Tyr Gly Ser Glu Glu Ser 1365 1370 1375 Pro Glu Pro Leu Pro Ile Pro Thr Leu Leu Val Gly Tyr Asp Lys Asp 1380 1385 1390 Phe Leu Thr Ile Ser Pro Phe Ser Leu Pro Phe Trp Glu Arg Leu Leu 1395 1400 1405 Leu Asp Pro Tyr Gly Gly His Arg Asp Val Ala Tyr Ile Val Val Cys 1410 1415 1420 Pro Glu Asn Glu Ala Leu Leu Glu Gly Ala Lys Thr Phe Phe Arg Asp 1425 1430 1435 1440 Leu Ser Ala Val Tyr Glu Met Cys Arg Leu Gly Gln His Lys Pro Ile 1445 1450 1455 Cys Lys Val Leu Arg Asp Gly Ile Met Arg Val Gly Lys Thr Val Ala 1460 1465 1470 Gln Lys Leu Thr Asp Glu Leu Val Ser Glu Trp Phe Asn Gln Pro Trp 1475 1480 1485 Ser Gly Glu Glu Asn Asp Asn His Ser Arg Leu Lys Leu Tyr Ala Gln 1490 1495 1500 Val Cys Arg His His Leu Ala Pro Tyr Leu Ala Thr Leu Gln Leu Asp 1505 1510 1515 1520 Ser Ser Leu Leu Ile Pro Pro Lys Tyr Gln Thr Pro Pro Ala Ala Ala 1525 1530 1535 Gln Gly Gln Ala Thr Pro Gly Asn Ala Gly Pro Leu Ala Pro Asn Gly 1540 1545 1550 Ser Ala Ala Pro Pro Ala Gly Ser Ala Phe Asn Pro Thr Ser Asn Ser 1555 1560 1565 Ser Ser Thr Asn Pro Ala Ala Ser Ser Ser Ala Ser Gly Ser Ser Val 1570 1575 1580 Pro Pro Val Ser Ser Ser Ala Ser Ala Pro Gly Ile Ser Gln Ile Ser 1585 1590 1595 1600 Thr Thr Ser Ser Ser Gly Phe Ser Gly Ser Val Gly Gly Gln Asn Pro 1605 1610 1615 Ser Thr Gly Gly Ile Ser Ala Asp Arg Thr Gln Gly Asn Ile Gly Cys 1620 1625 1630 Gly Gly Asp Thr Asp Pro Gly Gln Ser Ser Ser Gln Pro Ser Gln Asp 1635 1640 1645 Gly Gln Glu Ser Val Thr Glu Arg Glu Arg Ile Gly Ile Pro Thr Glu 1650 1655 1660 Pro Asp Ser Ala Asp Ser His Ala His Pro Pro Ala Val Val Ile Tyr 1665 1670 1675 1680 Met Val Asp Pro Phe Thr Tyr Ala Ala Glu Glu Asp Ser Thr Ser Gly 1685 1690 1695 Asn Phe Trp Leu Leu Ser Leu Met Arg Cys Tyr Thr Glu Met Leu Asp 1700 1705 1710 Asn Leu Pro Glu His Met Arg Asn Ser Phe Ile Leu Gln Ile Val Pro 1715 1720 1725 Cys Gln Tyr Met Leu Gln Thr Met Lys Asp Glu Gln Val Phe Tyr Ile 1730 1735 1740 Gln Tyr Leu Lys Ser Met Ala Phe Ser Val Tyr Cys Gln Cys Arg Arg 1745 1750 1755 1760 Pro Leu Pro Thr Gln Ile His Ile Lys Ser Leu Thr Gly Phe Gly Pro 1765 1770 1775 Ala Ala Ser Ile Glu Met Thr Leu Lys Asn Pro Glu Arg Pro Ser Pro 1780 1785 1790 Ile Gln Leu Tyr Ser Pro Pro Phe Ile Leu Ala Pro Ile Lys Asp Lys 1795 1800 1805 Gln Thr Glu Leu Gly Glu Thr Phe Gly Glu Ala Ser Gln Lys Tyr Asn 1810 1815 1820 Val Leu Phe Val Gly Tyr Cys Leu Ser His Asp Gln Arg Trp Leu Leu 1825 1830 1835 1840 Ala Ser Cys Thr Asp Leu His Gly Glu Leu Leu Glu Thr Cys Val Val 1845 1850 1855 Asn Ile Ala Leu Pro Asn Arg Ser Arg Arg Ser Lys Val Ser Ala Arg 1860 1865 1870 Lys Ile Gly Leu Gln Lys Leu Trp Glu Trp Cys Ile Gly Ile Val Gln 1875 1880 1885 Met Thr Ser Leu Pro Trp Arg Val Val Ile Gly Arg Leu Gly Arg Leu 1890 1895 1900 Gly His Gly Glu Leu Lys Asp Trp Ser Ile Leu Leu Gly Glu Cys Ser 1905 1910 1915 1920 Leu Gln Thr Ile Ser Lys Lys Leu Lys Asp Val Cys Arg Met Cys Gly 1925 1930 1935 Ile Ser Ala Ala Asp Ser Pro Ser Ile Leu Ser Ala Cys Leu Val Ala 1940 1945 1950 Met Glu Pro Gln Gly Ser Phe Val Val Met Pro Asp Ala Val Thr Met 1955 1960 1965 Gly Ser Val Phe Gly Arg Ser Thr Ala Leu Asn Met Gln Ser Ser Gln 1970 1975 1980 Leu Asn Thr Pro Gln Asp Ala Ser Cys Thr His Ile Leu Val Phe Pro 1985 1990 1995 2000 Thr Ser Ser Thr Ile Gln Val Ala Pro Ala Asn Tyr Pro Asn Glu Asp 2005 2010 2015 Gly Phe Ser Pro Asn Asn Asp Asp Met Phe Val Asp Leu Pro Phe Pro 2020 2025 2030 Asp Asp Met Asp Asn Asp Ile Gly Ile Leu Met Thr Gly Asn Leu His 2035 2040 2045 Ser Ser Pro Asn Ser Ser Pro Val Pro Ser Pro Gly Ser Pro Ser Gly 2050 2055 2060 Ile Gly Val Gly Ser His Phe Gln His Ser Arg Ser Gln Gly Glu Arg 2065 2070 2075 2080 Leu Leu Ser Arg Glu Ala Pro Glu Glu Leu Lys Gln Gln Pro Leu Ala 2085 2090 2095 Leu Gly Tyr Phe Val Ser Thr Ala Lys Ala Glu Asn Leu Pro Gln Trp 2100 2105 2110 Phe Trp Ser Ser Cys Pro Gln Ala Gln Asn Gln Cys Pro Leu Phe Leu 2115 2120 2125 Lys Ala Ser Leu His His His Ile Ser Val Ala Gln Thr Asp Glu Leu 2130 2135 2140 Leu Pro Ala Arg Asn Ser Gln Arg Val Pro His Pro Leu Asp Ser Lys 2145 2150 2155 2160 Thr Thr Ser Asp Val Leu Arg Phe Val Leu Glu Gln Tyr Asn Ala Leu 2165 2170 2175 Ser Trp Leu Thr Cys Asn Pro Ala Thr Gln Asp Arg Thr Ser Cys Leu 2180 2185 2190 Pro Val His Phe Val Val Leu Thr Gln Leu Tyr Asn Ala Ile Met Asn 2195 2200 2205 Ile Leu 2210 <210> 104 <211> 2151 <212> PRT <213> Homo sapiens <400> 104 Met Leu Ser Ser Gly Val Glu Thr Gln Pro Val Pro Leu Asp Ser Ser 1 5 10 15 Met Ser Ala Val Val Gln Glu Leu Tyr Ser Glu Leu Pro Val Ser Val 20 25 30 Ser Arg Glu Leu His Ala Asp Pro Glu Pro Ser Val Ile Pro Asp Val 35 40 45 Lys Pro Gly Ala Ser Ser Ser Leu Leu Ser Gln Asn Arg Ala Leu Pro 50 55 60 Leu Glu Leu Gln Arg Thr His Val Glu Ser Cys Cys Glu Glu Thr Tyr 65 70 75 80 Glu Thr Leu Asp His Gly Ser Glu Pro Gly Arg Cys Gly Leu Val Asp 85 90 95 Ser Thr Ala Gly Gly Ser Val Ala Ser Gly Ile Leu Asp Arg Ala Lys 100 105 110 Arg Ser Glu Ser Met Glu Pro Lys Val Phe Arg Asp Pro Gly Gly Gln 115 120 125 Ala Gly Ile Ile Arg Glu Pro Ser Glu Gly Ala Lys Glu Asp Pro His 130 135 140 Gln His Ser Thr Ala Ala Glu Glu Lys Thr Ser Pro Ser Gln Glu Asp 145 150 155 160 Leu Leu Met Gln Ser Ser Lys Glu Leu Ser His Val Asp Leu Pro Glu 165 170 175 Asp Phe Leu Arg Ser Lys Glu Gly Asn Val Gln Ile Thr Ala Glu Thr 180 185 190 Leu Leu Lys Ser Ala Glu Val Gln Gly Met Lys Val Asn Gly Thr Lys 195 200 205 Thr Asp Asn Asn Glu Gly His Lys Asn Gly Asn Val Ser Lys Asp Leu 210 215 220 Ser Ala Gly Cys Gly Glu Phe Gln Glu Val Asp Lys Ile Met Thr Ser 225 230 235 240 Asp Glu Val Ser Glu Thr Ser Thr Leu Val Thr Pro Glu Pro Leu Thr 245 250 255 Phe Val Asp Pro Val Leu Thr Glu Ala Thr Pro Lys Glu Lys Glu Cys 260 265 270 Glu Glu Leu Lys Ser Cys Pro Trp Leu Ser Leu Pro Gly Asn Ser Ala 275 280 285 Ile Ser Asn Val Asp Asn Gly Lys Glu Glu Leu Cys Lys Pro Asn Leu 290 295 300 Val Cys Glu Ala Asp Asp Asn His Gln Gln Leu His Gly His His Asn 305 310 315 320 Glu Gln Pro Ser Ser Thr His Asp Ser Pro Thr Ala Thr Ser Pro Leu 325 330 335 Lys Glu Asn Ser Glu Val Ser Cys Phe Thr Ser Asp Leu Ser Gly Pro 340 345 350 Glu Ser Arg Thr Ile Ser Leu Glu Asn Cys Gly Phe Glu Gly Gly Gly 355 360 365 Leu Leu Lys Arg Ser Ala Glu Lys Thr Asp Ser Ser Tyr Phe Tyr Arg 370 375 380 Gly Asp Asp Gln Gly Lys Asn Leu Ala Ser Arg Glu Glu Asn Glu Glu 385 390 395 400 Arg Leu Leu Ile Pro Arg Ser Glu Arg Gly Gly Pro Phe Leu Phe Asn 405 410 415 Ala Arg Glu Pro Glu Lys Glu Ile Ser Gly Arg Cys Ser Gly Glu Lys 420 425 430 Glu Pro Val Val Ser Pro Lys Glu Asn Ile His Asn Asn Cys Ile Gln 435 440 445 Asp Ser Leu His Thr Gly Asn Ser Ser Ser Leu Met Pro Asn Ser Phe 450 455 460 Thr Glu Ala Thr Glu Val Met Leu Asn Lys Asn Asp Leu Lys Ile Thr 465 470 475 480 Val His Val Gln Gly Asn Leu Thr Asn Pro Glu Asp His Lys Glu Thr 485 490 495 Phe Thr Asn Met Ser His Pro Gly Gly His Ser Glu Glu Ser Ser Phe 500 505 510 Ser Ser Leu Met Gln Ile Glu Glu Ala Gly Gln Thr Thr Pro Val Glu 515 520 525 Pro Asn Ile Leu Ser Lys Ser Phe Tyr Thr Lys Asp Cys Asn Ser Leu 530 535 540 Val Ser Ile Gln Arg Asn Leu Glu Gly Asn Thr Gln Leu Asn Glu Ala 545 550 555 560 Ser Cys Asn Asp Phe Leu Phe Glu Arg Lys Ser Ile Val Ser Leu Met 565 570 575 Pro Glu Asp Gln Ile Ser Pro Val Ser Glu Val Leu Lys Pro Lys Gln 580 585 590 Gly Thr Ala Leu Leu Leu Pro Ser Pro Glu Phe Asp Tyr Arg Pro Glu 595 600 605 Ser Glu Lys Val Ile Gln Thr Ser His Asp Asp Ile Pro Leu Leu Asp 610 615 620 Glu Gln Ser Ile Ala Cys Glu Met Asn Glu Leu Ser Cys Thr Asn Glu 625 630 635 640 Leu Val Val Asn Lys Val Glu Ser Glu Cys Val Leu Asn Gln Gln Val 645 650 655 Ser Leu Asn Ser Gln Glu His Ala Asn Leu Pro Thr Asp Ser Leu Leu 660 665 670 His Leu Asn Lys Glu Met Pro Leu Ala Thr Gly Arg Asp Ala His Gln 675 680 685 Ser His His Pro Pro Leu Glu Gly Arg Ala Asp Val Ile Ala Asp Ile 690 695 700 Gln Thr Ile Pro Ile Gln Thr Lys Ile Lys Asp Ile Ser Pro Pro Gly 705 710 715 720 Asn Gln Thr Cys Gly Ala Ser Ser Asn Cys Pro Thr Leu Asn Ile Lys 725 730 735 Pro Val Ser Leu Glu Arg Lys Lys Glu Met Ala Asp Ser Gly Thr Lys 740 745 750 Ala Leu His Ser Arg Leu Arg Ser Asn Lys Arg Glu Ala Ala Gly Phe 755 760 765 Pro Gln Val Val Ser Val Ile Glu Cys His Ser Val Gln Ser Gln Asp 770 775 780 Ile Ser Ser Cys His Arg Val Arg Lys Asn Val Ser Gln Glu Asn Met 785 790 795 800 Cys Ser Ala Ser Ala Ala Phe Lys Ser Ser Lys Ile Ser Leu Gln Val 805 810 815 Asp Asn Ser Leu Ile Thr Lys Tyr Glu Asn Ala Phe Gln His Arg Asp 820 825 830 His Cys Cys Gln Gly Thr Gly His Ser Val Glu Lys Ser Ser Cys Lys 835 840 845 Val Ser Tyr Thr Ser Gln Glu Arg Glu Leu Asp Gly Lys Glu Thr Asn 850 855 860 Gly Ser Leu Pro Gly Asp Lys Ile Arg Asn Lys Met Val Ala Gly Leu 865 870 875 880 Leu Asn Ser Gly Ile Ser Asn Lys Thr Ile His Thr Ser Ser Ser Ile 885 890 895 Lys Leu Ser Glu Glu Gly Leu Glu Gly Lys Glu Gln Asp Val Ser Lys 900 905 910 Glu Thr Val Phe Cys Lys Tyr Asn Ile Ser Asp His Ala Ile Gln Glu 915 920 925 Leu Asn Gln Thr Val Asn Ile Pro Gly Pro Glu Lys Val Leu Asp Gln 930 935 940 Ser Pro Thr Val Met Phe Ser Ser Phe Lys Asn Val Lys Ser Val Glu 945 950 955 960 Thr Leu Asp Gln Lys Ala Asp Glu Val Leu Asp Cys Gln Ser Asn Gln 965 970 975 Asn Arg Pro Asp Glu Cys Lys Ser Glu Gly Gln Ser Ala Lys Glu Met 980 985 990 Leu Ser Ser Asp Gln Arg Glu Thr Val Thr Glu Pro His Gly Glu Val 995 1000 1005 Asn His Asn Gln Lys Asp Leu Leu Val Ser Ser Gly Ser Asn Asn Ser 1010 1015 1020 Leu Pro Cys Gly Ser Pro Lys Lys Cys Asn Leu Lys Gly Ala Phe Val 1025 1030 1035 1040 Lys Met Ser Gly Cys Asp Glu Ser Thr Glu Gly Met Val Asp Ile Val 1045 1050 1055 Tyr Thr Asp Cys Ser Asn Lys Leu Ala Glu Gly Val Leu Asp Val Lys 1060 1065 1070 Ala Ser Asn Leu Leu Asp Cys Gly Ala Arg Gln Glu Lys Leu Ala Phe 1075 1080 1085 Gln Glu Asp Ser Arg Ser Thr Leu Ser Arg Arg Glu Leu Asp Ala Ala 1090 1095 1100 His Thr Gly Thr Thr Gly Gln Asp Ser Asp Phe Pro Val Thr Ala Ala 1105 1110 1115 1120 Ser Thr Val Asp Phe Leu Lys Ile Lys Lys Ser Cys Glu Glu Asn Val 1125 1130 1135 Cys Arg Ser Leu Lys Asp Cys Glu Met Glu Lys Cys Pro Asp Ser Cys 1140 1145 1150 Ala His Glu Met Glu Ser Val Ala Asp His Glu Pro Asn Lys Arg Ile 1155 1160 1165 Leu Gly Arg Val Asn Leu Ser Leu Asn Asp Ser His Tyr Gly Gln Gln 1170 1175 1180 Asp Lys Gly Thr Ser Leu Arg Glu Thr Gln Glu Met Thr Glu Gly Ser 1185 1190 1195 1200 Arg Leu Glu Pro Asn Ser Glu Phe Gly Lys Glu Ser Thr Phe Gly Ile 1205 1210 1215 Ser Ser Lys Glu Ser Met Ser Cys His Asp Glu Ser Ser Val Ser Leu 1220 1225 1230 Arg Ser Leu Lys Ser Ile Glu Ile Met Pro Ser Gln Glu Asn Ser Glu 1235 1240 1245 Thr Asn Val Asn Ser Glu Glu Thr Asp Leu Lys Asn Leu Cys Lys Pro 1250 1255 1260 Lys Asp Gly Glu Met Leu Cys Glu Asn Val Lys Asp Cys Thr Val Leu 1265 1270 1275 1280 Pro Glu Met Lys Glu Ile Val Ser Arg Asp Trp Ser Asn Ser Ser Asp 1285 1290 1295 Arg Asp Ser Val Cys Thr Cys Val Glu Lys Asn Ala Cys Lys Ala Cys 1300 1305 1310 His Pro His Glu Asn Ser Ser Asp Arg His Leu Pro Leu Thr Val Lys 1315 1320 1325 Thr Asp Ile Lys Val Lys Gly Glu Glu Thr Glu Glu His Gln Arg Gly 1330 1335 1340 Arg Leu Gly Tyr Leu Thr Val Gly Glu Gln Ser Glu Glu Leu Val Thr 1345 1350 1355 1360 Arg Glu Thr Gly Asp Gly Asp Pro Val Ser Asn Ile Ser Gln Thr His 1365 1370 1375 Phe Lys Cys Arg Gly Ile Leu Asn His Ala Glu Lys Gln Gln Ser Pro 1380 1385 1390 Glu Val Leu Asp Tyr Met Leu Gln Lys Glu Glu Lys Tyr Ile Arg Gln 1395 1400 1405 Gln Lys Ala His Thr Ile Ser Gln Gln Cys Ile Ser Ser Ser Leu Leu 1410 1415 1420 Leu Asp Asp Ala Gln Asn Gln Asn Gln Pro Lys Ala Asp Lys Asp Glu 1425 1430 1435 1440 Ser Thr Met Ile Asn Glu Ile Thr Leu Ala Lys Leu Ala Lys Asp Ser 1445 1450 1455 Ile Val Ala Gln Thr Gln Lys Leu Glu Asp Gln Lys Glu Glu Arg Leu 1460 1465 1470 His His Pro Leu Arg Lys Asp Thr Glu Ser Cys Thr Ser Pro Cys Leu 1475 1480 1485 Leu Gly Ala Pro Arg Lys Ala Gln Asp Pro Ser Ser Ala Gly Cys Asp 1490 1495 1500 Gln Ile His Gly Ala Phe Ala Lys Lys Gly Val Leu Pro Leu Lys Lys 1505 1510 1515 1520 Gln Pro His Arg Thr Cys Lys Lys Val Ser Tyr Gln Glu Gln Ile Ile 1525 1530 1535 Val Gly Arg Lys Ile Gly Lys Ile Arg Ser Ser Ala Phe Leu Lys Ser 1540 1545 1550 Ser Ser Asn Pro Ile Pro Thr Lys Ala His Arg Leu Leu Ser Leu Cys 1555 1560 1565 Thr Leu Ser Ala Pro Thr Arg Leu Glu Pro Glu Thr Ala Pro Thr Lys 1570 1575 1580 Ser Leu Val Ser His Ile Pro Lys Gln Met Ser Thr Pro Cys His Pro 1585 1590 1595 1600 Leu Arg Ser Leu Asn Phe Arg Lys Thr Thr Lys Glu Ser Ala Leu Leu 1605 1610 1615 Asn Lys Leu Ser Ile Leu Ala Ser Lys Leu Ala Pro Ala Met Lys Thr 1620 1625 1630 Gln Lys Leu Arg Tyr Arg Arg Cys Ser Ser Glu Leu Leu Pro Met Ala 1635 1640 1645 Lys Ser Tyr Lys Arg Leu Arg Tyr Lys Arg Leu Leu Asp Gly Phe Ser 1650 1655 1660 Ser Ser Thr Glu Gln Leu Asn Pro Tyr Leu Ala Ala Ser Gly Trp Asp 1665 1670 1675 1680 Lys Arg Pro Asn Ser Lys Pro Met Ala Leu Tyr Ser Leu Glu Ser Ile 1685 1690 1695 Lys Met Thr Phe Ile Asp Leu Ser Asn Lys Met Pro Ser Leu Leu Phe 1700 1705 1710 Gly Ser Glu Ile Phe Pro Val Ser Phe His Val Lys Ser Ser Ser Ser 1715 1720 1725 Asp Cys Thr Thr Glu Ser Ser Arg Thr Phe Pro Glu His Cys Ala Pro 1730 1735 1740 Ala Arg Leu Ala Leu Gly Glu Ala Leu Gln Cys Pro Ser Gln Pro Pro 1745 1750 1755 1760 Lys Trp Thr Phe Ser Phe Phe Leu Ser His Gly Cys Pro Gly Met Ala 1765 1770 1775 Thr Phe Arg Glu Asp Thr Gly Val His Ser Gln Thr His Thr Gln Ala 1780 1785 1790 Pro Pro Gln Pro Pro Ala Pro Leu Gln Asp Tyr Gly Gly Thr Ala Ile 1795 1800 1805 Val Gln Thr Arg Ala Asp Cys Ser Val Leu Gly Leu His Thr Leu Leu 1810 1815 1820 Ala Leu Cys Ser Pro Gly Cys Tyr Arg Ile Trp Thr Lys Lys Arg Ser 1825 1830 1835 1840 Phe Ser Ser His Met Pro Thr Met Gln Arg Leu Phe Met Thr Gln Phe 1845 1850 1855 Thr Gln Gly Leu Lys Gly Leu Arg Ser Pro Ala Ser Ile Ala Asp Lys 1860 1865 1870 Val Phe Cys Ser Leu Pro Tyr Ser Val Gly Arg Val Leu Ser Ile Trp 1875 1880 1885 Ser Gln His Gly Pro Ser Val Cys Ser Phe Glu Ile Ser Ser Leu His 1890 1895 1900 Ser Pro His Cys Lys Arg Gln Pro Ser Leu Gly Thr Thr Ser Ser His 1905 1910 1915 1920 Thr Met Leu Pro Tyr Val Pro Leu Pro Gly Met Glu Ala Thr Tyr Asn 1925 1930 1935 Thr Ser Gly Ser Gln Thr Arg Leu Glu Pro Pro Phe Pro Ala Leu Val 1940 1945 1950 Pro Lys Ser Cys Leu Val Ala Glu Ser Ala Val Ser Lys Leu Leu Leu 1955 1960 1965 Ser Ala Ser Glu Phe Gln Val Arg Gly Leu Asp Glu Leu Asp Gly Val 1970 1975 1980 Lys Ala Ala Cys Pro Cys Pro Gln Ser Ser Pro Pro Glu Gln Lys Glu 1985 1990 1995 2000 Ala Glu Pro Glu Lys Arg Pro Lys Lys Val Ser Gln Ile Arg Ile Arg 2005 2010 2015 Lys Thr Ile Pro Arg Pro Asp Pro Asn Leu Thr Pro Met Gly Leu Pro 2020 2025 2030 Arg Pro Lys Arg Leu Lys Lys Lys Glu Phe Ser Leu Glu Glu Ile Tyr 2035 2040 2045 Thr Asn Lys Asn Tyr Lys Ser Pro Pro Ala Asn Arg Cys Leu Glu Thr 2050 2055 2060 Ile Phe Glu Glu Pro Lys Glu Arg Asn Gly Thr Leu Ile Ser Ile Ser 2065 2070 2075 2080 Gln Gln Lys Arg Lys Arg Val Leu Glu Phe Gln Asp Phe Thr Val Pro 2085 2090 2095 Arg Lys Arg Arg Ala Arg Gly Lys Val Lys Val Ala Gly Ser Phe Thr 2100 2105 2110 Arg Ala Gln Lys Ala Ala Val Gln Ser Arg Glu Leu Asp Ala Leu Leu 2115 2120 2125 Ile Gln Lys Leu Met Glu Leu Glu Thr Phe Phe Ala Lys Glu Glu Glu 2130 2135 2140 Gln Glu Gln Ser Ser Gly Cys 2145 2150 <210> 105 <211> 3433 <212> PRT <213> Homo sapiens <400> 105 Met Ala Lys Tyr Gly Glu His Glu Ala Ser Pro Asp Asn Gly Gln Asn 1 5 10 15 Glu Phe Ser Asp Ile Ile Lys Ser Arg Ser Asp Glu His Asn Asp Val 20 25 30 Gln Lys Lys Thr Phe Thr Lys Trp Ile Asn Ala Arg Phe Ser Lys Ser 35 40 45 Gly Lys Pro Pro Ile Asn Asp Met Phe Thr Asp Leu Lys Asp Gly Arg 50 55 60 Lys Leu Leu Asp Leu Leu Glu Gly Leu Thr Gly Thr Ser Leu Pro Lys 65 70 75 80 Glu Arg Gly Ser Thr Arg Val His Ala Leu Asn Asn Val Asn Arg Val 85 90 95 Leu Gln Val Leu His Gln Asn Asn Val Glu Leu Val Asn Ile Gly Gly 100 105 110 Thr Asp Ile Val Asp Gly Asn His Lys Leu Thr Leu Gly Leu Leu Trp 115 120 125 Ser Ile Ile Leu His Trp Gln Val Lys Asp Val Met Lys Asp Val Met 130 135 140 Ser Asp Leu Gln Gln Thr Asn Ser Glu Lys Ile Leu Leu Ser Trp Val 145 150 155 160 Arg Gln Thr Thr Arg Pro Tyr Ser Gln Val Asn Val Leu Asn Phe Thr 165 170 175 Thr Ser Trp Thr Asp Gly Leu Ala Phe Asn Ala Val Leu His Arg His 180 185 190 Lys Pro Asp Leu Phe Ser Trp Asp Lys Val Val Lys Met Ser Pro Ile 195 200 205 Glu Arg Leu Glu His Ala Phe Ser Lys Ala Gln Thr Tyr Leu Gly Ile 210 215 220 Glu Lys Leu Leu Asp Pro Glu Asp Val Ala Val Arg Leu Pro Asp Lys 225 230 235 240 Lys Ser Ile Ile Met Tyr Leu Thr Ser Leu Phe Glu Val Leu Pro Gln 245 250 255 Gln Val Thr Ile Asp Ala Ile Arg Glu Val Glu Thr Leu Pro Arg Lys 260 265 270 Tyr Lys Lys Glu Cys Glu Glu Glu Ala Ile Asn Ile Gln Ser Thr Ala 275 280 285 Pro Glu Glu Glu His Glu Ser Pro Arg Ala Glu Thr Pro Ser Thr Val 290 295 300 Thr Glu Val Asp Met Asp Leu Asp Ser Tyr Gln Ile Ala Leu Glu Glu 305 310 315 320 Val Leu Thr Trp Leu Leu Ser Ala Glu Asp Thr Phe Gln Glu Gln Asp 325 330 335 Asp Ile Ser Asp Asp Val Glu Glu Val Lys Asp Gln Phe Ala Thr His 340 345 350 Glu Ala Phe Met Met Glu Leu Thr Ala His Gln Ser Ser Val Gly Ser 355 360 365 Val Leu Gln Ala Gly Asn Gln Leu Ile Thr Gln Gly Thr Leu Ser Asp 370 375 380 Glu Glu Glu Phe Glu Ile Gln Glu Gln Met Thr Leu Leu Asn Ala Arg 385 390 395 400 Trp Glu Ala Leu Arg Val Glu Ser Met Asp Arg Gln Ser Arg Leu His 405 410 415 Asp Val Leu Met Glu Leu Gln Lys Lys Gln Leu Gln Gln Leu Ser Ala 420 425 430 Trp Leu Thr Leu Thr Glu Glu Arg Ile Gln Lys Met Glu Thr Cys Pro 435 440 445 Leu Asp Asp Asp Val Lys Ser Leu Gln Lys Leu Leu Glu Glu His Lys 450 455 460 Ser Leu Gln Ser Asp Leu Glu Ala Glu Gln Val Lys Val Asn Ser Leu 465 470 475 480 Thr His Met Val Val Ile Val Asp Glu Asn Ser Gly Glu Ser Ala Thr 485 490 495 Ala Ile Leu Glu Asp Gln Leu Gln Lys Leu Gly Glu Arg Trp Thr Ala 500 505 510 Val Cys Arg Trp Thr Glu Glu Arg Trp Asn Arg Leu Gln Glu Ile Asn 515 520 525 Ile Leu Trp Gln Glu Leu Leu Glu Glu Gln Cys Leu Leu Lys Ala Trp 530 535 540 Leu Thr Glu Lys Glu Glu Ala Leu Asn Lys Val Gln Thr Ser Asn Phe 545 550 555 560 Lys Asp Gln Lys Glu Leu Ser Val Ser Val Arg Arg Leu Ala Ile Leu 565 570 575 Lys Glu Asp Met Glu Met Lys Arg Gln Thr Leu Asp Gln Leu Ser Glu 580 585 590 Ile Gly Gln Asp Val Gly Gln Leu Leu Asp Asn Ser Lys Ala Ser Lys 595 600 605 Lys Ile Asn Ser Asp Ser Glu Glu Leu Thr Gln Arg Trp Asp Ser Leu 610 615 620 Val Gln Arg Leu Glu Asp Ser Ser Asn Gln Val Thr Gln Ala Val Ala 625 630 635 640 Lys Leu Gly Met Ser Gln Ile Pro Gln Lys Asp Leu Leu Glu Thr Val 645 650 655 Arg Val Arg Glu Gln Ala Ile Thr Lys Lys Ser Lys Gln Glu Leu Pro 660 665 670 Pro Pro Pro Pro Pro Lys Lys Arg Gln Ile His Val Asp Ile Glu Ala 675 680 685 Lys Lys Lys Phe Asp Ala Ile Ser Ala Glu Leu Leu Asn Trp Ile Leu 690 695 700 Lys Trp Lys Thr Ala Ile Gln Thr Thr Glu Ile Lys Glu Tyr Met Lys 705 710 715 720 Met Gln Asp Thr Ser Glu Met Lys Lys Lys Leu Lys Ala Leu Glu Lys 725 730 735 Glu Gln Arg Glu Arg Ile Pro Arg Ala Asp Glu Leu Asn Gln Thr Gly 740 745 750 Gln Ile Leu Val Glu Gln Met Gly Lys Glu Gly Leu Pro Thr Glu Glu 755 760 765 Ile Lys Asn Val Leu Glu Lys Val Ser Ser Glu Trp Lys Asn Val Ser 770 775 780 Gln His Leu Glu Asp Leu Glu Arg Lys Ile Gln Leu Gln Glu Asp Ile 785 790 795 800 Asn Ala Tyr Phe Lys Gln Leu Asp Glu Leu Glu Lys Val Ile Lys Thr 805 810 815 Lys Glu Glu Trp Val Lys His Thr Ser Ile Ser Glu Ser Ser Arg Gln 820 825 830 Ser Leu Pro Ser Leu Lys Asp Ser Cys Gln Arg Glu Leu Thr Asn Leu 835 840 845 Leu Gly Leu His Pro Lys Ile Glu Met Ala Arg Ala Ser Cys Ser Ala 850 855 860 Leu Met Ser Gln Pro Ser Ala Pro Asp Phe Val Gln Arg Gly Phe Asp 865 870 875 880 Ser Phe Leu Gly Arg Tyr Gln Ala Val Gln Glu Ala Val Glu Asp Arg 885 890 895 Gln Gln His Leu Glu Asn Glu Leu Lys Gly Gln Pro Gly His Ala Tyr 900 905 910 Leu Glu Thr Leu Lys Thr Leu Lys Asp Val Leu Asn Asp Ser Glu Asn 915 920 925 Lys Ala Gln Val Ser Leu Asn Val Leu Asn Asp Leu Ala Lys Val Glu 930 935 940 Lys Ala Leu Gln Glu Lys Lys Thr Leu Asp Glu Ile Leu Glu Asn Gln 945 950 955 960 Lys Pro Ala Leu His Lys Leu Ala Glu Glu Thr Lys Ala Leu Glu Lys 965 970 975 Asn Val His Pro Asp Val Glu Lys Leu Tyr Lys Gln Glu Phe Asp Asp 980 985 990 Val Gln Gly Lys Trp Asn Lys Leu Lys Val Leu Val Ser Lys Asp Leu 995 1000 1005 His Leu Leu Glu Glu Ile Ala Leu Thr Leu Arg Ala Phe Glu Ala Asp 1010 1015 1020 Ser Thr Val Ile Glu Lys Trp Met Asp Gly Val Lys Asp Phe Leu Met 1025 1030 1035 1040 Lys Gln Gln Ala Ala Gln Gly Asp Asp Ala Gly Leu Gln Arg Gln Leu 1045 1050 1055 Asp Gln Cys Ser Ala Phe Val Asn Glu Ile Glu Thr Ile Glu Ser Ser 1060 1065 1070 Leu Lys Asn Met Lys Glu Ile Glu Thr Asn Leu Arg Ser Gly Pro Val 1075 1080 1085 Ala Gly Ile Lys Thr Trp Val Gln Thr Arg Leu Gly Asp Tyr Gln Thr 1090 1095 1100 Gln Leu Glu Lys Leu Ser Lys Glu Ile Ala Thr Gln Lys Ser Arg Leu 1105 1110 1115 1120 Ser Glu Ser Gln Glu Lys Ala Ala Asn Leu Lys Lys Asp Leu Ala Glu 1125 1130 1135 Met Gln Glu Trp Met Thr Gln Ala Glu Glu Glu Tyr Leu Glu Arg Asp 1140 1145 1150 Phe Glu Tyr Lys Ser Pro Glu Glu Leu Glu Ser Ala Val Glu Glu Met 1155 1160 1165 Lys Arg Ala Lys Glu Asp Val Leu Gln Lys Glu Val Arg Val Lys Ile 1170 1175 1180 Leu Lys Asp Asn Ile Lys Leu Leu Ala Ala Lys Val Pro Ser Gly Gly 1185 1190 1195 1200 Gln Glu Leu Thr Ser Glu Leu Asn Val Val Leu Glu Asn Tyr Gln Leu 1205 1210 1215 Leu Cys Asn Arg Ile Arg Gly Lys Cys His Thr Leu Glu Glu Val Trp 1220 1225 1230 Ser Cys Trp Ile Glu Leu Leu His Tyr Leu Asp Leu Glu Thr Thr Trp 1235 1240 1245 Leu Asn Thr Leu Glu Glu Arg Met Lys Ser Thr Glu Val Leu Pro Glu 1250 1255 1260 Lys Thr Asp Ala Val Asn Glu Ala Leu Glu Ser Leu Glu Ser Val Leu 1265 1270 1275 1280 Arg His Pro Ala Asp Asn Arg Thr Gln Ile Arg Glu Leu Gly Gln Thr 1285 1290 1295 Leu Ile Asp Gly Gly Ile Leu Asp Asp Ile Ile Ser Glu Lys Leu Glu 1300 1305 1310 Ala Phe Asn Ser Arg Tyr Glu Asp Leu Ser His Leu Ala Glu Ser Lys 1315 1320 1325 Gln Ile Ser Leu Glu Lys Gln Leu Gln Val Leu Arg Glu Thr Asp Gln 1330 1335 1340 Met Leu Gln Val Leu Gln Glu Ser Leu Gly Glu Leu Asp Lys Gln Leu 1345 1350 1355 1360 Thr Thr Tyr Leu Thr Asp Arg Ile Asp Ala Phe Gln Val Pro Gln Glu 1365 1370 1375 Ala Gln Lys Ile Gln Ala Glu Ile Ser Ala His Glu Leu Thr Leu Glu 1380 1385 1390 Glu Leu Arg Arg Asn Met Arg Ser Gln Pro Leu Thr Ser Pro Glu Ser 1395 1400 1405 Arg Thr Ala Arg Gly Gly Ser Gln Met Asp Val Leu Gln Arg Lys Leu 1410 1415 1420 Arg Glu Val Ser Thr Lys Phe Gln Leu Phe Gln Lys Pro Ala Asn Phe 1425 1430 1435 1440 Glu Gln Arg Met Leu Asp Cys Lys Arg Val Leu Asp Gly Val Lys Ala 1445 1450 1455 Glu Leu His Val Leu Asp Val Lys Asp Val Asp Pro Asp Val Ile Gln 1460 1465 1470 Thr His Leu Asp Lys Cys Met Lys Leu Tyr Lys Thr Leu Ser Glu Val 1475 1480 1485 Lys Leu Glu Val Glu Thr Val Ile Lys Thr Gly Arg His Ile Val Gln 1490 1495 1500 Lys Gln Gln Thr Asp Asn Pro Lys Gly Met Asp Glu Gln Leu Thr Ser 1505 1510 1515 1520 Leu Lys Val Leu Tyr Asn Asp Leu Gly Ala Gln Val Thr Glu Gly Lys 1525 1530 1535 Gln Asp Leu Glu Arg Ala Ser Gln Leu Ala Arg Lys Met Lys Lys Glu 1540 1545 1550 Ala Ala Ser Leu Ser Glu Trp Leu Ser Ala Thr Glu Thr Glu Leu Val 1555 1560 1565 Gln Lys Ser Thr Ser Glu Gly Leu Leu Gly Asp Leu Asp Thr Glu Ile 1570 1575 1580 Ser Trp Ala Lys Asn Val Leu Lys Asp Leu Glu Lys Arg Lys Ala Asp 1585 1590 1595 1600 Leu Asn Thr Ile Thr Glu Ser Ser Ala Ala Leu Gln Asn Leu Ile Glu 1605 1610 1615 Gly Ser Glu Pro Ile Leu Glu Glu Arg Leu Cys Val Leu Asn Ala Gly 1620 1625 1630 Trp Ser Arg Val Arg Thr Trp Thr Glu Asp Trp Cys Asn Thr Leu Met 1635 1640 1645 Asn His Gln Asn Gln Leu Glu Ile Phe Asp Gly Asn Val Ala His Ile 1650 1655 1660 Ser Thr Trp Leu Tyr Gln Ala Glu Ala Leu Leu Asp Glu Ile Glu Lys 1665 1670 1675 1680 Lys Pro Thr Ser Lys Gln Glu Glu Ile Val Lys Arg Leu Val Ser Glu 1685 1690 1695 Leu Asp Asp Ala Asn Leu Gln Val Glu Asn Val Arg Asp Gln Ala Leu 1700 1705 1710 Ile Leu Met Asn Ala Arg Gly Ser Ser Ser Arg Glu Leu Val Glu Pro 1715 1720 1725 Lys Leu Ala Glu Leu Asn Arg Asn Phe Glu Lys Val Ser Gln His Ile 1730 1735 1740 Lys Ser Ala Lys Leu Leu Ile Ala Gln Glu Pro Leu Tyr Gln Cys Leu 1745 1750 1755 1760 Val Thr Thr Glu Thr Phe Glu Thr Gly Val Pro Phe Ser Asp Leu Glu 1765 1770 1775 Lys Leu Glu Asn Asp Ile Glu Asn Met Leu Lys Phe Val Glu Lys His 1780 1785 1790 Leu Glu Ser Ser Asp Glu Asp Glu Lys Met Asp Glu Glu Ser Ala Gln 1795 1800 1805 Ile Glu Glu Val Leu Gln Arg Gly Glu Glu Met Leu His Gln Pro Met 1810 1815 1820 Glu Asp Asn Lys Lys Glu Lys Ile Arg Leu Gln Leu Leu Leu Leu His 1825 1830 1835 1840 Thr Arg Tyr Asn Lys Ile Lys Ala Ile Pro Ile Gln Gln Arg Lys Met 1845 1850 1855 Gly Gln Leu Ala Ser Gly Ile Arg Ser Ser Leu Leu Pro Thr Asp Tyr 1860 1865 1870 Leu Val Glu Ile Asn Lys Ile Leu Leu Cys Met Asp Asp Val Glu Leu 1875 1880 1885 Ser Leu Asn Val Pro Glu Leu Asn Thr Ala Ile Tyr Glu Asp Phe Ser 1890 1895 1900 Phe Gln Glu Asp Ser Leu Lys Asn Ile Lys Asp Gln Leu Asp Lys Leu 1905 1910 1915 1920 Gly Glu Gln Ile Ala Val Ile His Glu Lys Gln Pro Asp Val Ile Leu 1925 1930 1935 Glu Ala Ser Gly Pro Glu Ala Ile Gln Ile Arg Asp Thr Leu Thr Gln 1940 1945 1950 Leu Asn Ala Lys Trp Asp Arg Ile Asn Arg Met Tyr Ser Asp Arg Lys 1955 1960 1965 Gly Cys Phe Asp Arg Ala Met Glu Glu Trp Arg Gln Phe His Cys Asp 1970 1975 1980 Leu Asn Asp Leu Thr Gln Trp Ile Thr Glu Ala Glu Glu Leu Leu Val 1985 1990 1995 2000 Asp Thr Cys Ala Pro Gly Gly Ser Leu Asp Leu Glu Lys Ala Arg Ile 2005 2010 2015 His Gln Gln Glu Leu Glu Val Gly Ile Ser Ser His Gln Pro Ser Phe 2020 2025 2030 Ala Ala Leu Asn Arg Thr Gly Asp Gly Ile Val Gln Lys Leu Ser Gln 2035 2040 2045 Ala Asp Gly Ser Phe Leu Lys Glu Lys Leu Ala Gly Leu Asn Gln Arg 2050 2055 2060 Trp Asp Ala Ile Val Ala Glu Val Lys Asp Arg Gln Pro Arg Leu Lys 2065 2070 2075 2080 Gly Glu Ser Lys Gln Val Met Lys Tyr Arg His Gln Leu Asp Glu Ile 2085 2090 2095 Ile Cys Trp Leu Thr Lys Ala Glu His Ala Met Gln Lys Arg Ser Thr 2100 2105 2110 Thr Glu Leu Gly Glu Asn Leu Gln Glu Leu Arg Asp Leu Thr Gln Glu 2115 2120 2125 Met Glu Val His Ala Glu Lys Leu Lys Trp Leu Asn Arg Thr Glu Leu 2130 2135 2140 Glu Met Leu Ser Asp Lys Ser Leu Ser Leu Pro Glu Arg Asp Lys Ile 2145 2150 2155 2160 Ser Glu Ser Leu Arg Thr Val Asn Met Thr Trp Asn Lys Ile Cys Arg 2165 2170 2175 Glu Val Pro Thr Thr Leu Lys Glu Cys Ile Gln Glu Pro Ser Ser Val 2180 2185 2190 Ser Gln Thr Arg Ile Ala Ala His Pro Asn Val Gln Lys Val Val Leu 2195 2200 2205 Val Ser Ser Ala Ser Asp Ile Pro Val Gln Ser His Arg Thr Ser Glu 2210 2215 2220 Ile Ser Ile Pro Ala Asp Leu Asp Lys Thr Ile Thr Glu Leu Ala Asp 2225 2230 2235 2240 Trp Leu Val Leu Ile Asp Gln Met Leu Lys Ser Asn Ile Val Thr Val 2245 2250 2255 Gly Asp Val Glu Glu Ile Asn Lys Thr Val Ser Arg Met Lys Ile Thr 2260 2265 2270 Lys Ala Asp Leu Glu Gln Arg His Pro Gln Leu Asp Tyr Val Phe Thr 2275 2280 2285 Leu Ala Gln Asn Leu Lys Asn Lys Ala Ser Ser Ser Asp Met Arg Thr 2290 2295 2300 Ala Ile Thr Glu Lys Leu Glu Arg Val Lys Asn Gln Trp Asp Gly Thr 2305 2310 2315 2320 Gln His Gly Val Glu Leu Arg Gln Gln Gln Leu Glu Asp Met Ile Ile 2325 2330 2335 Asp Ser Leu Gln Trp Asp Asp His Arg Glu Glu Thr Glu Glu Leu Met 2340 2345 2350 Arg Lys Tyr Glu Ala Arg Leu Tyr Ile Leu Gln Gln Ala Arg Arg Asp 2355 2360 2365 Pro Leu Thr Lys Gln Ile Ser Asp Asn Gln Ile Leu Leu Gln Glu Leu 2370 2375 2380 Gly Pro Gly Asp Gly Ile Val Met Ala Phe Asp Asn Val Leu Gln Lys 2385 2390 2395 2400 Leu Leu Glu Glu Tyr Gly Ser Asp Asp Thr Arg Asn Val Lys Glu Thr 2405 2410 2415 Thr Glu Tyr Leu Lys Thr Ser Trp Ile Asn Leu Lys Gln Ser Ile Ala 2420 2425 2430 Asp Arg Gln Asn Ala Leu Glu Ala Glu Trp Arg Thr Val Gln Ala Ser 2435 2440 2445 Arg Arg Asp Leu Glu Asn Phe Leu Lys Trp Ile Gln Glu Ala Glu Thr 2450 2455 2460 Thr Val Asn Val Leu Val Asp Ala Ser His Arg Glu Asn Ala Leu Gln 2465 2470 2475 2480 Asp Ser Ile Leu Ala Arg Glu Leu Lys Gln Gln Met Gln Asp Ile Gln 2485 2490 2495 Ala Glu Ile Asp Ala His Asn Asp Ile Phe Lys Ser Ile Asp Gly Asn 2500 2505 2510 Arg Gln Lys Met Val Lys Ala Leu Gly Asn Ser Glu Glu Ala Thr Met 2515 2520 2525 Leu Gln His Arg Leu Asp Asp Met Asn Gln Arg Trp Asn Asp Leu Lys 2530 2535 2540 Ala Lys Ser Ala Ser Ile Arg Ala His Leu Glu Ala Ser Ala Glu Lys 2545 2550 2555 2560 Trp Asn Arg Leu Leu Met Ser Leu Glu Glu Leu Ile Lys Trp Leu Asn 2565 2570 2575 Met Lys Asp Glu Glu Leu Lys Lys Gln Met Pro Ile Gly Gly Asp Val 2580 2585 2590 Pro Ala Leu Gln Leu Gln Tyr Asp His Cys Lys Ala Leu Arg Arg Glu 2595 2600 2605 Leu Lys Glu Lys Glu Tyr Ser Val Leu Asn Ala Val Asp Gln Ala Arg 2610 2615 2620 Val Phe Leu Ala Asp Gln Pro Ile Glu Ala Pro Glu Glu Pro Arg Arg 2625 2630 2635 2640 Asn Leu Gln Ser Lys Thr Glu Leu Thr Pro Glu Glu Arg Ala Gln Lys 2645 2650 2655 Ile Ala Lys Ala Met Arg Lys Gln Ser Ser Glu Val Lys Glu Lys Trp 2660 2665 2670 Glu Ser Leu Asn Ala Val Thr Ser Asn Trp Gln Lys Gln Val Asp Lys 2675 2680 2685 Ala Leu Glu Lys Leu Arg Asp Leu Gln Gly Ala Met Asp Asp Leu Asp 2690 2695 2700 Ala Asp Met Lys Glu Ala Glu Ser Val Arg Asn Gly Trp Lys Pro Val 2705 2710 2715 2720 Gly Asp Leu Leu Ile Asp Ser Leu Gln Asp His Ile Glu Lys Ile Met 2725 2730 2735 Ala Phe Arg Glu Glu Ile Ala Pro Ile Asn Phe Lys Val Lys Thr Val 2740 2745 2750 Asn Asp Leu Ser Ser Gln Leu Ser Pro Leu Asp Leu His Pro Ser Leu 2755 2760 2765 Lys Met Ser Arg Gln Leu Asp Asp Leu Asn Met Arg Trp Lys Leu Leu 2770 2775 2780 Gln Val Ser Val Asp Asp Arg Leu Lys Gln Leu Gln Glu Ala His Arg 2785 2790 2795 2800 Asp Phe Gly Pro Ser Ser Gln His Phe Leu Ser Thr Ser Val Gln Leu 2805 2810 2815 Pro Trp Gln Arg Ser Ile Ser His Asn Lys Val Pro Tyr Tyr Ile Asn 2820 2825 2830 His Gln Thr Gln Thr Thr Cys Trp Asp His Pro Lys Met Thr Glu Leu 2835 2840 2845 Phe Gln Ser Leu Ala Asp Leu Asn Asn Val Arg Phe Ser Ala Tyr Arg 2850 2855 2860 Thr Ala Ile Lys Ile Arg Arg Leu Gln Lys Ala Leu Cys Leu Asp Leu 2865 2870 2875 2880 Leu Glu Leu Ser Thr Thr Asn Glu Ile Phe Lys Gln His Lys Leu Asn 2885 2890 2895 Gln Asn Asp Gln Leu Leu Ser Val Pro Asp Val Ile Asn Cys Leu Thr 2900 2905 2910 Thr Thr Tyr Asp Gly Leu Glu Gln Met His Lys Asp Leu Val Asn Val 2915 2920 2925 Pro Leu Cys Val Asp Met Cys Leu Asn Trp Leu Leu Asn Val Tyr Asp 2930 2935 2940 Thr Gly Arg Thr Gly Lys Ile Arg Val Gln Ser Leu Lys Ile Gly Leu 2945 2950 2955 2960 Met Ser Leu Ser Lys Gly Leu Leu Glu Glu Lys Tyr Arg Tyr Leu Phe 2965 2970 2975 Lys Glu Val Ala Gly Pro Thr Glu Met Cys Asp Gln Arg Gln Leu Gly 2980 2985 2990 Leu Leu Leu His Asp Ala Ile Gln Ile Pro Arg Gln Leu Gly Glu Val 2995 3000 3005 Ala Ala Phe Gly Gly Ser Asn Ile Glu Pro Ser Val Arg Ser Cys Phe 3010 3015 3020 Gln Gln Asn Asn Asn Lys Pro Glu Ile Ser Val Lys Glu Phe Ile Asp 3025 3030 3035 3040 Trp Met His Leu Glu Pro Gln Ser Met Val Trp Leu Pro Val Leu His 3045 3050 3055 Arg Val Ala Ala Ala Glu Thr Ala Lys His Gln Ala Lys Cys Asn Ile 3060 3065 3070 Cys Lys Glu Cys Pro Ile Val Gly Phe Arg Tyr Arg Ser Leu Lys His 3075 3080 3085 Phe Asn Tyr Asp Val Cys Gln Ser Cys Phe Phe Ser Gly Arg Thr Ala 3090 3095 3100 Lys Gly His Lys Leu His Tyr Pro Met Val Glu Tyr Cys Ile Pro Thr 3105 3110 3115 3120 Thr Ser Gly Glu Asp Val Arg Asp Phe Thr Lys Val Leu Lys Asn Lys 3125 3130 3135 Phe Arg Ser Lys Lys Tyr Phe Ala Lys His Pro Arg Leu Gly Tyr Leu 3140 3145 3150 Pro Val Gln Thr Val Leu Glu Gly Asp Asn Leu Glu Thr Pro Ile Thr 3155 3160 3165 Leu Ile Ser Met Trp Pro Glu His Tyr Asp Pro Ser Gln Ser Pro Gln 3170 3175 3180 Leu Phe His Asp Asp Thr His Ser Arg Ile Glu Gln Tyr Ala Thr Arg 3185 3190 3195 3200 Leu Ala Gln Met Glu Arg Thr Asn Gly Ser Phe Leu Thr Asp Ser Ser 3205 3210 3215 Ser Thr Thr Gly Ser Val Glu Asp Glu His Ala Leu Ile Gln Gln Tyr 3220 3225 3230 Cys Gln Thr Leu Gly Gly Glu Ser Pro Val Ser Gln Pro Gln Ser Pro 3235 3240 3245 Ala Gln Ile Leu Lys Ser Val Glu Arg Glu Glu Arg Gly Glu Leu Glu 3250 3255 3260 Arg Ile Ile Ala Asp Leu Glu Glu Glu Gln Arg Asn Leu Gln Val Glu 3265 3270 3275 3280 Tyr Glu Gln Leu Lys Asp Gln His Leu Arg Arg Gly Leu Pro Val Gly 3285 3290 3295 Ser Pro Pro Glu Ser Ile Ile Ser Pro His His Thr Ser Glu Asp Ser 3300 3305 3310 Glu Leu Ile Ala Glu Ala Lys Leu Leu Arg Gln His Lys Gly Arg Leu 3315 3320 3325 Glu Ala Arg Met Gln Ile Leu Glu Asp His Asn Lys Gln Leu Glu Ser 3330 3335 3340 Gln Leu His Arg Leu Arg Gln Leu Leu Glu Gln Pro Glu Ser Asp Ser 3345 3350 3355 3360 Arg Ile Asn Gly Val Ser Pro Trp Ala Ser Pro Gln His Ser Ala Leu 3365 3370 3375 Ser Tyr Ser Leu Asp Pro Asp Ala Ser Gly Pro Gln Phe His Gln Ala 3380 3385 3390 Ala Gly Glu Asp Leu Leu Ala Pro Pro His Asp Thr Ser Thr Asp Leu 3395 3400 3405 Thr Glu Val Met Glu Gln Ile His Ser Thr Phe Pro Ser Cys Cys Pro 3410 3415 3420 Asn Val Pro Ser Arg Pro Gln Ala Met 3425 3430

Claims (7)

  1. 서열번호 48 또는 69의 아미노산 서열로 구성된 단백질을 포함하는 당뇨병성 망막병증(diabetic retinopathy) 검출용 바이오 마커 조성물.
  2. 삭제
  3. 제1항에 있어서, 검체로서 혈액 또는 뇨(urine)를 사용하는 것을 특징으로 하는 바이오 마커 조성물.
  4. 서열번호 48 또는 69의 아미노산 서열로 구성된 단백질과 특이적으로 결합하는 분자를 포함하는, 당뇨병성 망막병증(diabetic retinopathy) 진단 키트.
  5. 제4항에 있어서, 상기 분자가 모노클로날 항체, 폴리클로날 항체, 기질, 리 간드, 또는 보조인자(cofactor)인 것을 특징으로 하는 진단 키트.
  6. 삭제
  7. 제4항 또는 제5항에 있어서, 검체로서 혈액 또는 뇨(urine)를 사용하는 것을 특징으로 하는 진단 키트.
KR1020070087512A 2007-08-30 2007-08-30 당뇨병성 망막병증 검출용 바이오 마커 조성물 및 진단키트 KR100961926B1 (ko)

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US12/733,330 US20100179307A1 (en) 2007-08-30 2008-08-28 Biomaker composition for detecting diabetic retinopathy and diagnostic kit therefor
PCT/KR2008/005046 WO2009028880A2 (en) 2007-08-30 2008-08-28 Biomarker composition for detecting diabetic retinopathy and diagnostic kit therefor
US13/354,016 US20120183973A1 (en) 2007-08-30 2012-01-19 Biomarker composition for detecting diabetic retinopathy and diagnostic kit therefor

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KR101343137B1 (ko) * 2012-01-03 2013-12-20 서울대학교산학협력단 당뇨망막병증의 조기 진단용 마커 및 이의 용도

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