KR102569948B1 - 암 검출 방법 - Google Patents

암 검출 방법 Download PDF

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KR102569948B1
KR102569948B1 KR1020160057080A KR20160057080A KR102569948B1 KR 102569948 B1 KR102569948 B1 KR 102569948B1 KR 1020160057080 A KR1020160057080 A KR 1020160057080A KR 20160057080 A KR20160057080 A KR 20160057080A KR 102569948 B1 KR102569948 B1 KR 102569948B1
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안나 데일리
린지 러더퍼드
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어센던트 다이아그노스틱스, 엘엘씨
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Abstract

암이 결여된 대조군 시료에 비해, 일련의 바이오마커의 적어도 하나의 수준을 측정함으로써 암, 특히 유방암을 검출하기 위한 방법 및 키트가 제공된다. 바이오마커의 발현은 암 부재 개체의 발현 수준에 비해, 암 존재 개체로부터의 시료에서 증가 또는 감소한다. 시료는 단리된 눈물 시료 또는 안구 세정액 (ocular wash)와 같은 안구 시료가 최적이지만, 타액, 또는 기타 체액으로부터 일 수 있다. 키트는 채집 관 및 프로테아제 억제제 또는 단백질 안정화제를 포함할 수 있다.

Description

암 검출 방법 {METHODS OF DETECTING CANCER}
본 출원은 단백질, 및 단백질의 단백질 분해적 분해에 의해 제조되는 상기 단백질의 펩티드 단편을 포함하며, 상기 단백질 및 펩티드 단편, 둘 모두 개체에서 암을 진단하는 데 또는 암의 존재에 대해 모니터링하는 데 유용하다.
유방조영상(mammogram) 스크리닝은 전형적으로 75%의 감도 및 약 98%의 특이도를 가지는 바, 이에 유방조영상당 대략 5%의 위양성률이 발생하게 된다 (문헌 [Brown, Houn, Sickles, & Kessler, 1995]; [Kolb, Lichy, & Newhouse, 2002]; [Luftner & Possinger, 2002]). 유방 조직 유형, 더욱 구체적으로, 밀도 또한 유방조영술의 성능에 크게 영향을 미친다. 유방 밀도 정도는 미국 영상 의학 협회(American College of Radiology)의 유방 영상 판독과 자료 체계(Breast Imaging Reporting and Data System: BI-RADS)를 사용하여 분류된다. 상기 체계는 4개의 부류 1-4로 이루어진다: 여기서, 카테고리 1은 대개가 지방질인 것이고 (<25% 치밀); 카테고리 2는 산재형 섬유선질 밀도인 것이고 (25-50% 치밀); 카테고리 3은 불균질 치밀형인 것이고 (51-75% 치밀), 카테고리 4는 고등도 치밀형인 것이다 (>75% 치밀) (문헌 [Bigenwald, 2008]; [Klifa, 2010; Scheel, 2014]).
지방질 유방 조직을 가진 여성의 경우, 환자가 매년 실시되는 스크리닝과 순응성일 때, 유방조영술은 효과적인 스크리닝 도구가 될 수 있다 (문헌 [Tabar, 2001; Pisano, 2005]). 그러나, 유방 밀도가 증가함에 따라, 유방조영술의 효능이 감소되며, 이로써 후속 영상화는 증가되고, 더욱 중요하게는, 암 진단 오류가 증가하게 된다. 고위험 환자에 대한 유방조영술 감도는 카테고리 1의 경우, 31%, 카테고리 2의 경우, 27%, 카테고리 3의 경우, 20%, 및 카테고리 4의 경우, 12.5%만큼 낮은 것으로 밝혀져 있다 (문헌 [Bigenwald, 2008]). 여성 집단 중 대략 50%가 치밀형 유방 조직으로 간주되는 카테고리 3 및 4에 있다 (문헌 [Vachon, 2007]). 현재, 상기 여성들을 위한 최상의 스크리닝 옵션은 MRI인데, 이는 유방조영술보다 최대 10배까지 더 비쌀 수 있다 (문헌 [Beignwald, 2008]). 75% 초과로 치밀 조직을 가진 여성이 치밀 조직을 더 적게 가진 여성보다 유방암이 발병될 위험이 4 내지 6배 더 크기 때문에, 우수한 스크리닝 옵션이 없다는 것은 식감한 문제가 된다 (문헌 [Boyd, 2007]).
미국에서는 위양성을 평가하는 후속 영상화를 위한 비용으로 10억이 들었고, 생검 단독을 위해서는 추가로 160억 달러가 지출되었다. 2010년 160만 건의 생검이 수행되었는데, 겨우 16% 정도만이 (단지 261,000건) 암을 갖는 것으로 나타났다 (문헌 [Grady, 2012]). 영상화의 진단적 파라미터 증가에 관한 해답은 유전자 및 프로테옴 정보, 더욱 구체적으로, 바이오마커에 초점을 맞춘 영상 진단 이전 및 이후에서 찾을 수 있다 (문헌 [Armstrong, Handorf, Chen, & Bristol Demeter, 2013]; [Li, Zhang, Rosenzweig, Wang, & Chan, 2002]).
조직 및 혈청은 일반적으로 바이오마커 연구를 위해 논리상 가장 적합한 신체의 한 부분이지만, 상기 두 매질의 동적 범위는 매우 크기 때문에 발견하기가 상당히 어렵다 (문헌 [Schiess, Wollscheid, & Aebersold, 2009]). 해답은 예컨대, 타액 및 눈물과 같이 덜 복잡합 생물학적 유체에 있을 수 있다. 눈물의 프로테옴이 이전에 광범위하게 조사된 바 있기 때문에 (문헌 [Boehm et al., 2012; 2011]; [Lebrecht, Boehm, Schmidt, Koelbl, & Grus, 2009a]; [Lebrecht et al., 2009b]; [Wu & Zhang, 2007]), 눈물의 진단용 매질로서의 용도는 신규한 적용은 아니다. 본 출원에서는 암에 대한 반응으로 눈물 기반 바이오마커로 이루어진 패널을 검출하기 위한 정량적 검정법을 개시한다. 이러한 정량적 정보로부터 공인 실험 개선 개정(Certified Laboratory Improvement Amendments: CLIA) 프로토콜에 대한 골격이 정의될 것이다.
본원에서는 대상체가 암을 갖는지 여부를 결정하는 방법을 제공한다. 본 방법은 대상체로부터 샘플을 수득하는 단계, 및 하기로부터 선택되고, 표 1에 열거된 적어도 1개의 마커의 수준을 검출하는 단계를 포함한다: Ig 람다 쇄 V-IV 영역 Hil (LV403), Ig 중쇄 V-III BRO (HV305), Ig 중쇄 V-III VH26 (HV303), β-2-마이크로글로불린 (B2MG), 리포칼린-1 (LCN1), 아연-α-2-당단백질 (ZA2G), 시스타틴 B (CYTB), 항류코프로테이나제 (SLP1), 갈렉틴-3 (LEG3), 히스티딘 트리아드 뉴클레오티드-결합 단백질 1 (D6RD60), S100A9 (S10A9), S100A8 (S10A8), 갈렉틴-3-결합 단백질 (LG3BP), Ig 알파-1 쇄 C 영역의 클러스터 (IGHA1), Ig 카파 쇄 V-III 영역 HAH의 클러스터 (KV312), VEGF 공조절형 케모카인 1 (VCC1), L-락테이트 데히드로게나제 A 쇄 (LDHA), 알도-케토리덕타제 패밀리 1 구성원 C (AKR1C1), 루트레틴 (B1AKD8), L-락테이트 데히드로게나제 B 쇄 (LDHB), 망막 데히드로게나제 1 (AL1A1), 미규명 단백질 (B4E1Z4), 알파-1-항키모트립신 (AACT), 슈퍼옥시드 디스뮤타제 [Cu-Zn] (SODC), SPARC-유사 단백질 1 (SPRL1), Ig 중쇄 V-III 영역 TIL (HV304), 케라틴 (K1C9), 시스타틴-SN (CYTN), 알파-악티닌-4 (ACTN4), Ig 람다-3 쇄 C 영역 (단편) (IGLC3), 면역글로불린 람다-유사 폴리펩티드 5 (IGLL5), 알콜 데히드로게나제 1C (ADHIG), 말레이트 데히드로게나제, 미토콘드리아 (MDHM), 칼모듈린-유사 단백질 5 (CALL5), 알파-1-항트립신 (A1AT), 알파-1B-당단백질 (A1BG), 류신이 풍부한 알파-2-당단백질 (A2GL), 소형 유비퀴틴-관련 변형인자 3 (A8MU27), 앞 구배 단백질 2 동족체 (AGR2), 프로필린-1 (PROF1), Ig 람다 쇄 V-III 영역 LOI의 클러스터 (LV302), 프로트롬빈 (E9PIT3), 헤모펙신 (HEMO), Ig 감마-2 쇄 C 영역 (IGHG2), 유비퀴틴-40S 리보솜 단백질 S27a (RPS27A), 아파민 (AFAM), 아포지질단백질 A-I (APOA1), 아포지질단백질 A-IV (APOA4), 플라빈 리덕타제 (NADPH)(BLVRB), 프로사포신 (PSAP), 라크리틴 (LACRT), 60S 산성 리보솜 단백질 P1 (RLA1), 인터-알파-트립신 억제제 중쇄 H2 (ITIH2), 뮤신-유사 단백질 1 (MUCL1), S100 A6 (S100A6), Na(+)/H(+) 교환 조절 보조인자 NHE-RF1 (NHRF1), 티오레독신 도메인-함유 단백질 17 (I3L0K2), 림프구-특이 단백질 (LSP1), 합토글로빈의 클러스터 (H3BS21), 미오신 조절 경쇄 12A (J2QRS3), 리보뉴클레아제 억제제 (RINI), 알파-에놀라제 (ENOA), Ig 카파 쇄 V-I 영역 EU의 클러스터 (KV106), 알콜 데히드로게나제 부류 4 뮤/시그마 쇄 (ADH7), 단백질 AMBP (AMBP), 안지오텐시노겐 (ANGT), 항트롬빈-III (ANT3), 아포지질단백질 A-II (APOA2), 칼페스타틴 (B7Z574), 뇌 산성 가용성 단백질 1 (BASP1), 알파-2-HS-당단백질 (C9JV77), 칼레티쿨린 (CALR), 칼페인-1 촉매성 서브유니트 (CAN1), 세포 분열 조절 단백질 42 동족체 (CDC42), 보체 C3 (CO3), 코로닌-1A (COR1A), 프로그램화된 세포 사멸 6-상호작용 단백질 (DCD), 데핀신 1 (DEF1), F-박스 유일 단백질 50 (FBX50), 감마-글루타밀시클로트랜스퍼라제 (GGCT), 글루타티온 리덕타제, 미토콘드리아 (GSHR), 케라틴, II형 세포골격 1 (K2C1), UMP-CMP 키나제 (KCY), 메소텔린 (MSLN), N-아세틸무라모일-L-알라닌 아미다제 (PGRP2), 니코티네이트 포스포리보실트랜스퍼라제 (PNCB), 인터-알파-트립신 억제제 중쇄 H1 (ITIH1), 리보뉴클레아제 T2 (RNASET2), 슈퍼옥시드 디스뮤타제 [Mn], 미토콘드리아 (SODM), 소형 프롤린이 풍부한 단백질 3 (SPRR3), Src 기질 코탁틴 (SRC8), 튜뷸린 베타-4B 쇄의 클러스터 (TBB4B), 트로포미오신 알파-3 쇄 (TPM3), 세로트랜스페린 (TRFE), 글루타티온 S-트랜스퍼라제 P (THIO), 비트로넥틴 (VTNC), 비타민 D 결합 단백질 (Q6LDC6), 인터-알파-트립신 억제제 중쇄 H4 (ITIH4), 메탈로프로테아제 억제제 (TIMP1), 열 쇼크 단백질 90 (HSP90), 카텝신 B (CATB), 셀룰로플라즈민 (CERU), 칼프로텍틴, 14-3-3 시그마 (1433S), 알파-2-hs-당단백질 (FETUA), 알파-2-마크로글로불린 (A2MG), 트랜스티레틴 (TTHY). 상기 마커 수준이 암 결여 대상체로부터의 대조군 샘플 중의 수준과 비교하여 변화하였다면, 대상체는 암을 가질 가능성이 있는 것이다. 샘플은 최적으로는 안구 샘플, 예컨대, 단리된 눈물 샘플 또는 안구 세액이지만, 이는 또한 타액, 또는 다른 체액으로부터의 것일 수 있다. 안구 샘플은 눈물샘, 및 림프계와 연결된 다른 조직으로부터 분비물을 포함하는 눈물 샘플을 나타낸다.
본원에 기술된 방법을 수행하기 위한 키트 또한 제공한다. 키트는 샘플 수집 플랫폼, 프로테아제 억제제 또는 다른 단백질 안정화제를 포함할 수 있는, 수집 및 추출용 관, 샘플 추출용 시약 및 시험 기구를 포함할 수 있다.
도 1: 실험 1에서 확인된 하기 단백질에 대한 스펙트럼 강도의 ANOVA: (a) Ig 중쇄 V-IV 영역 HiL, (b) Ig 중쇄 영역 V-III 영역 BRO, (c) Ig 중쇄 V-III 영역 VH26, (d) 항류코프로테이나제, (e) β2 마이크로글로불린, (f) 칼모듈린 유사 단백질 5, (g) 리포칼린 1, (h) 시스타틴 B, (i) 갈렉틴 3, (j) 아연-α 2 당단백질.
도 2: Ig 중쇄 V-IV 영역 HiL, Ig 중쇄 영역 V-III 영역 BRO, Ig 중쇄 V-III 영역 VH26, 항류코프로테이나제, β2 마이크로글로불린, 칼모듈린 유사 단백질 5, 리포칼린 1, 시스타틴 B, 갈렉틴 3, 아연-α 2 당단백질을 사용하여 수행된 실험 1로부터의, 암, 양성, 및 대조군에 대한 ROC 곡선
도 3: 실험 1에서 시험된 75개의 샘플 중 66개에 대한 유방 밀도 분포에 관한 모자이크 플롯.
도 4: 실험 2에서 확인된 단백질에 대한 스펙트럼 강도의 ANOVA. 제시된 단백질은 (A) 14-3-3 단백질 시그마 (b) 6-포스포글루코네이트 데히드로게나제, 탈카르복실화 (c) 알파-악티닌-4 (d) 망막 데히드로게나제 (e) 아르기니노숙시네이트 신타제 (f) 베타-2-마이크로글로불린 (g) 칼모듈린 (h) 셀룰로플라즈민 (i) 코필린 (j) 시스타틴-SN (k) 에놀라제 1 (l) 겔솔린 (m) 열 쇼크 단백질 베타-1 (n) Ig 알파-1 쇄 C 영역 (o) 라크리틴 (p) 리소자임 (Q) 기저막-특이 헤파린 술페이트 프로테오글리칸 코어 단백질 (R) 중합체 면역글로불린 수용체 (s) 프로필린 1 (t) S100A8 (u) S100A9 (v) 세크레토글로빈 패밀리 1D 구성원 1 (w) VEGF 공조절형 케모카인 1 (x) 히스티딘 트리아드 뉴클레오티드-결합 단백질 1 (y) 데핀신 1 (z) L-락테이트 데히드로게나제 A 쇄 (aa) SPARC-유사 단백질 1 (bb) 아넥신 5 (cc) Ig 중쇄 V-III 영역 TIL (dd) 인터-알파-트립신 억제제 중쇄 1 (ee) 알파-1B-당단백질 (ff) 알파-1-항트립신.
도 5: 유방암 및 대조군 샘플에서 ELISA에 의해 측정된 S100A9의 발현 수준을 비교하는 ANOVA.
도 6: 유방암 및 대조군 샘플에서 ELISA에 의해 측정된 LG3BP의 발현 수준을 비교하는 ANOVA.
도 7: S100A9에 대한 ROC 곡선.
도 8: LG3BP에 대한 ROC 곡선.
도 9: 조합된 S100A9 및 LG3BP에 대한 ROC 곡선.
도 10: 유방 조직 카테고리에 기초한 S100A9 발현에 대한 ANOVA.
도 11: 유방 조직 카테고리에 기초한 LG3BP 발현에 대한 ANOVA.
본원에서는 안구 샘플로부터의 단백질, 및 트립신 분해에 의해 수득된 펩티드 단편을 제공한다. 제조된 폴리펩티드는 하기, 및 표 1에 열거된 것으로부터 선택된다: Ig 람다 쇄 V-IV 영역 Hil (LV403), Ig 중쇄 V-III BRO (HV305), Ig 중쇄 V-III VH26 (HV303), β-2-마이크로글로불린 (B2MG), 리포칼린-1 (LCN1), 아연-α-2-당단백질 (ZA2G), 시스타틴 B (CYTB), 항류코프로테이나제 (SLP1), 갈렉틴-3 (LEG3), 히스티딘 트리아드 뉴클레오티드-결합 단백질 1 (D6RD60), S100A9 (S10A9), S100A8 (S10A8), 갈렉틴-3-결합 단백질 (LG3BP), Ig 알파-1 쇄 C 영역의 클러스터 (IGHA1), Ig 카파 쇄 V-III 영역 HAH의 클러스터 (KV312), VEGF 공조절형 케모카인 1 (VCC1), L-락테이트 데히드로게나제 A 쇄 (LDHA), 알도-케토리덕타제 패밀리 1 구성원 C (AKR1C1), 루트레틴 (B1AKD8), L-락테이트 데히드로게나제 B 쇄 (LDHB), 망막 데히드로게나제 1 (AL1A1), 미규명 단백질 (B4E1Z4), 알파-1-항키모트립신 (AACT), 슈퍼옥시드 디스뮤타제 [Cu-Zn] (SODC), SPARC-유사 단백질 1 (SPRL1), Ig 중쇄 V-III 영역 TIL (HV304), 케라틴 (K1C9), 시스타틴-SN (CYTN), 알파-악티닌-4 (ACTN4), Ig 람다-3 쇄 C 영역 (단편) (IGLC3), 면역글로불린 람다-유사 폴리펩티드 5 (IGLL5), 알콜 데히드로게나제 1C (ADHIG), 말레이트 데히드로게나제, 미토콘드리아 (MDHM), 칼모듈린-유사 단백질 5 (CALL5), 알파-1-항트립신 (A1AT), 알파-1B-당단백질 (A1BG), 류신이 풍부한 알파-2-당단백질 (A2GL), 소형 유비퀴틴-관련 변형인자 3 (A8MU27), 앞 구배 단백질 2 동족체 (AGR2), 프로필린-1(PROF1), Ig 람다 쇄 V-III 영역 LOI의 클러스터 (LV302), 프로트롬빈 (E9PIT3), 헤모펙신 (HEMO), Ig 감마-2 쇄 C 영역 (IGHG2), 유비퀴틴-40S 리보솜 단백질 S27a (RPS27A), 아파민 (AFAM), 아포지질단백질 A-I (APOA1), 아포지질단백질 A-IV (APOA4), 플라빈 리덕타제 (NADPH)(BLVRB), 프로사포신 (PSAP), 라크리틴 (LACRT), 60S 산성 리보솜 단백질 P1 (RLA1), 인터-알파-트립신 억제제 중쇄 H2 (ITIH2), 뮤신-유사 단백질 1 (MUCL1), S100 A6 (S100A6), Na(+)/H(+) 교환 조절 보조인자 NHE-RF1 (NHRF1), 티오레독신 도메인-함유 단백질 17 (I3L0K2), 림프구-특이 단백질 (LSP1), 합토글로빈의 클러스터 (H3BS21), 미오신 조절 경쇄 12A (J2QRS3), 리보뉴클레아제 억제제 (RINI), 알파-에놀라제 (ENOA), Ig 카파 쇄 V-I 영역 EU의 클러스터 (KV106), 알콜 데히드로게나제 부류 4 뮤/시그마 쇄 (ADH7), 단백질 AMBP (AMBP), 안지오텐시노겐 (ANGT), 항트롬빈-III (ANT3), 아포지질단백질 A-II (APOA2), 칼페스타틴 (B7Z574), 뇌 산성 가용성 단백질 1 (BASP1), 알파-2-HS-당단백질 (C9JV77), 칼레티쿨린 (CALR), 칼페인-1 촉매성 서브유니트 (CAN1), 세포 분열 조절 단백질 42 동족체 (CDC42), 보체 C3 (CO3), 코로닌-1A (COR1A), 프로그램화된 세포 사멸 6-상호작용 단백질 (DCD), 데핀신 1 (DEF1), F-박스 유일 단백질 50 (FBX50), 감마-글루타밀시클로트랜스퍼라제 (GGCT), 글루타티온 리덕타제, 미토콘드리아 (GSHR), 케라틴, II형 세포골격 1 (K2C1), UMP-CMP 키나제 (KCY), 메소텔린 (MSLN), N-아세틸무라모일-L-알라닌 아미다제 (PGRP2), 니코티네이트 포스포리보실트랜스퍼라제 (PNCB), 인터-알파-트립신 억제제 중쇄 H1 (ITIH1), 리보뉴클레아제 T2 (RNASET2), 슈퍼옥시드 디스뮤타제 [Mn], 미토콘드리아 (SODM), 소형 프롤린이 풍부한 단백질 3 (SPRR3), Src 기질 코탁틴 (SRC8), 튜뷸린 베타-4B 쇄의 클러스터 (TBB4B), 트로포미오신 알파-3 쇄 (TPM3), 세로트랜스페린 (TRFE), 글루타티온 S-트랜스퍼라제 P (THIO), 비트로넥틴 (VTNC), 비타민 D 결합 단백질 (Q6LDC6), 인터-알파-트립신 억제제 중쇄 H4 (ITIH4), 메탈로프로테아제 억제제 (TIMP1), 열 쇼크 단백질 90 (HSP90), 카텝신 B (CATB), 셀룰로플라즈민 (CERU), 칼프로텍틴, 14-3-3 시그마 (1433S), 알파-2-hs-당단백질 (FETUA), 알파-2-마크로글로불린 (A2MG), 트랜스티레틴 (TTHY). 암 샘플에서 하향 조절된 것으로 확인된 단백질의 트립신 서열 및 전장의 아미노산 서열을 별첨 I에 제공한다.
대조군과 비교하여 유방암의 존재에 대한 반응으로 생물학적 샘플 중 증가 또는 감소되어 있는 단백질 및 펩티드는 실시예에 제시되어 있다. 상기 단백질 및 펩티드는 바이오마커이며, 이는 환자 또는 다른 대상체의 질환 상태를 결정하는 데 사용될 것이다.
대상체로는 인간, 가축, 예컨대, 고양이, 개, 소, 돼지, 또는 암에 걸리기 쉬운 다른 동물을 포함한다. "환자"는 질환, 또는 암 진단을 받았거나, 또는 암에 걸렸는지 여부에 대해 검사받게 되는 대상체를 나타낸다. 따라서, 대상체 및 환자라는 용어는 본원에서 상호교환적으로 사용될 수 있다. 대상체는 암을 갖는 것으로 의심받는 것일 수 있다. 대상체는 유방암, 청각 신경종, 급성 림프아구성 백혈병, 급성 골수성 백혈병, 부신 종양, AIDS-관련 암, 기저 세포 암종, 양성 혈액 장애, 방광암, 골암, (전이성 및 원발성) 뇌 종양, 유방암, 원발성 기점 불명의 암, 자궁경부암, 만성 림프구성 백혈병, 만성 골수성 백혈병, 결장직장암, 식도암, 담낭암 및 담관암, 위장 신경 내분비 종양, GERD, 바레트(Barrett's) 식도 및 이완불능증, 임신성 융모성 질환, 두부경부암, 카포시 육종, 신장암, 백혈병, 간암, 간 전이, 저등급 신경아교종, 폐암, 림프종, 남성 유방암, 흑색종, 메르켈 세포 암종, 중피종, 다발성 골수종, 골수형성이상 증후군, 난소암, 췌장암, 췌장 낭종, 뇌하수체 종양, 전립샘암, 폐 신경내분비 종양, 희귀 혈액 장애, 피부암, 연조직 육종, 척추 종양, 편평 세포 암종, 위암(stomach cancer) (위암(gastric cancer)), 고환암 (생식 세포 종양), 흉선종 및 다른 흉선 종양, 기관 질환, 자궁암 (자궁내막암),　자궁 육종을 비롯한, 암을 갖는 것으로 의심받는 것일 수 있다. 대상체는 유방암 발병 위험이 증가된 것일 수 있다. 예를 들어, 대상체는 양성 유방조영술 결과 때문에, 유방 중 소괴 검출에 의해, 예컨대, BRCA와 같은, 암 위험을 증가시키는 것으로 알려져 있는 유전자에 대하여 양성 반응을 보임에 따라 암 위험이 증가된 것이거나, 또는 암을 갖는 것으로 의심되는 것, 또는 이미 절제술, 생검, 또는 암을 제거하는 다른 수술을 받은 것일 수 있다. 대상체는 암 치료를 받고 있거나, 이전에 받은 것일 수 있고, 여기서, 방법 및 키트는 치료 진행을 모니터링하거나, 또는 별법으로, 암의 재발 또는 확산을 모니터링하는 데 사용된다.
본원에서는 또한 눈물 분비물 중에서 확인된 단백질 또는 폴리펩티드의 발현 수준을 결정하는 데 사용하기 위한 눈물 샘플 수집 방법 및 수집용 키트를 제공한다. 프로테아제 억제제 또는 단백질 안정화제를 함유하는 수집용 스트립 및 수집관의 용도를 개시한다. 키트는 눈물 분비물을 수집하기 위해 눈과 접촉된 수집 스트립으로부터 유방암 바이오마커를 용리시키기 위한 완충제 또는 시약을 추가로 함유한다. 안강으로부터 단백질을 수집하기 위한 장치의 디자인 뿐만 아니라, 수집 장치 및 용리 완충제를 수납하는 용기와 함께 하는 상기 장치의 패키징을 개시한다.
본원에 개시된 방법은 삼중 4극 LC-MS/MS 플랫폼을 사용하여 CLIA 기반 프로토콜에서 단일로 또는 다중으로 상기 암 바이오마커를 사용하는 것을 포함하며, 이는 중앙 실험실 검사 시설에서 수행될 것이다. 본 실시양태에서 개체로부터 수집된 안구 샘플은 상기 검사 시설로 배송될 수 있다. 별첨 I에 제시되어 있는 것과 같은, 확인된 단백질 및 그의 차후의 단백질 분해 단편은 삼중 4극에서 제조된 진단용 펩티드의 정량적 분석을 위해 사용된다. 역치 값 또는 상대적인 값 또는 실제값은 하기로부터 선택되고, 표 1에 열거된 폴리펩티드: Ig 람다 쇄 V-IV 영역 Hil (LV403), Ig 중쇄 V-III BRO (HV305), Ig 중쇄 V-III VH26 (HV303), β-2-마이크로글로불린 (B2MG), 리포칼린-1 (LCN1), 아연-α-2-당단백질 (ZA2G), 시스타틴 B (CYTB), 항류코프로테이나제 (SLP1), 갈렉틴-3 (LEG3), 히스티딘 트리아드 뉴클레오티드-결합 단백질 1 (D6RD60), S100A9 (S10A9), S100A8 (S10A8), 갈렉틴-3-결합 단백질 (LG3BP), Ig 알파-1 쇄 C 영역의 클러스터 (IGHA1), Ig 카파 쇄 V-III 영역 HAH의 클러스터 (KV312), VEGF 공조절형 케모카인 1 (VCC1), L-락테이트 데히드로게나제 A 쇄 (LDHA), 알도-케토리덕타제 패밀리 1 구성원 C (AKR1C1), 루트레틴 (B1AKD8), L-락테이트 데히드로게나제 B 쇄 (LDHB), 망막 데히드로게나제 1 (AL1A1), 미규명 단백질 (B4E1Z4), 알파-1-항키모트립신 (AACT), 슈퍼옥시드 디스뮤타제 [Cu-Zn] (SODC), SPARC-유사 단백질 1 (SPRL1), Ig 중쇄 V-III 영역 TIL (HV304), 케라틴 (K1C9), 시스타틴-SN (CYTN), 알파-악티닌-4 (ACTN4), Ig 람다-3 쇄 C 영역 (단편) (IGLC3), 면역글로불린 람다-유사 폴리펩티드 5 (IGLL5), 알콜 데히드로게나제 1C (ADHIG), 말레이트 데히드로게나제, 미토콘드리아 (MDHM), 칼모듈린-유사 단백질 5 (CALL5), 알파-1-항트립신 (A1AT), 알파-1B-당단백질 (A1BG), 류신이 풍부한 알파-2-당단백질 (A2GL), 소형 유비퀴틴-관련 변형인자 3 (A8MU27), 앞 구배 단백질 2 동족체 (AGR2), 프로필린-1 (PROF1), Ig 람다 쇄 V-III 영역 LOI의 클러스터 (LV302), 프로트롬빈 (E9PIT3), 헤모펙신 (HEMO), Ig 감마-2 쇄 C 영역 (IGHG2), 유비퀴틴-40S 리보솜 단백질 S27a (RPS27A), 아파민 (AFAM), 아포지질단백질 A-I (APOA1), 아포지질단백질 A-IV (APOA4), 플라빈 리덕타제 (NADPH)(BLVRB), 프로사포신 (PSAP), 라크리틴 (LACRT), 60S 산성 리보솜 단백질 P1 (RLA1), 인터-알파-트립신 억제제 중쇄 H2 (ITIH2), 뮤신-유사 단백질 1 (MUCL1), S100 A6 (S100A6), Na(+)/H(+) 교환 조절 보조인자 NHE-RF1 (NHRF1), 티오레독신 도메인-함유 단백질 17 (I3L0K2), 림프구-특이 단백질 (LSP1), 합토글로빈의 클러스터 (H3BS21), 미오신 조절 경쇄 12A (J2QRS3), 리보뉴클레아제 억제제 (RINI), 알파-에놀라제 (ENOA), Ig 카파 쇄 V-I 영역 EU의 클러스터 (KV106), 알콜 데히드로게나제 부류 4 뮤/시그마 쇄 (ADH7), 단백질 AMBP (AMBP), 안지오텐시노겐 (ANGT), 항트롬빈-III (ANT3), 아포지질단백질 A-II (APOA2), 칼페스타틴 (B7Z574), 뇌 산성 가용성 단백질 1 (BASP1), 알파-2-HS-당단백질 (C9JV77), 칼레티쿨린 (CALR), 칼페인-1 촉매성 서브유니트 (CAN1), 세포 분열 조절 단백질 42 동족체 (CDC42), 보체 C3 (CO3), 코로닌-1A (COR1A), 프로그램화된 세포 사멸 6-상호작용 단백질 (DCD), 데핀신 1 (DEF1), F-박스 유일 단백질 50 (FBX50), 감마-글루타밀시클로트랜스퍼라제 (GGCT), 글루타티온 리덕타제, 미토콘드리아 (GSHR), 케라틴, II형 세포골격 1 (K2C1), UMP-CMP 키나제 (KCY), 메소텔린 (MSLN), N-아세틸무라모일-L-알라닌 아미다제 (PGRP2), 니코티네이트 포스포리보실트랜스퍼라제 (PNCB), 인터-알파-트립신 억제제 중쇄 H1 (ITIH1), 리보뉴클레아제 T2 (RNASET2), 슈퍼옥시드 디스뮤타제 [Mn], 미토콘드리아 (SODM), 소형 프롤린이 풍부한 단백질 3 (SPRR3), Src 기질 코탁틴 (SRC8), 튜뷸린 베타-4B 쇄의 클러스터 (TBB4B), 트로포미오신 알파-3 쇄 (TPM3), 세로트랜스페린 (TRFE), 글루타티온 S-트랜스퍼라제 P (THIO), 비트로넥틴 (VTNC), 비타민 D 결합 단백질 (Q6LDC6), 인터-알파-트립신 억제제 중쇄 H4 (ITIH4), 메탈로프로테아제 억제제 (TIMP1), 열 쇼크 단백질 90 (HSP90), 카텝신 B (CATB), 셀룰로플라즈민 (CERU), 칼프로텍틴, 14-3-3 시그마 (1433S), 알파-2-hs-당단백질 (FETUA), 알파-2-마크로글로불린 (A2MG), 트랜스티레틴 (TTHY)과 직접적으로 관련이 있는 폴리펩티드 농도로 정의될 수 있거나, 또는 샘플은 직접적으로 비암성 대조군과 비교될 수 있다. 보고서 형태의 정량적 정보는 환자 치료 경로를 결정하는 데 도움을 주기 위해 의사에게 제공될 수 있다. 의사는 상기 결과에 기초하여 치료를 결정할 수 있고, 최종 단계는 대상체에게 적절한 항암 치료제를 투여하는 것을 포함할 수 있다.
대체 실시양태에서, 하기로부터 선택되고, 표 1에 열거된 폴리펩티드: Ig 람다 쇄 V-IV 영역 Hil (LV403), Ig 중쇄 V-III BRO (HV305), Ig 중쇄 V-III VH26 (HV303), β-2-마이크로글로불린 (B2MG), 리포칼린-1 (LCN1), 아연-α-2-당단백질 (ZA2G), 시스타틴 B (CYTB), 항류코프로테이나제 (SLP1), 갈렉틴-3 (LEG3), 히스티딘 트리아드 뉴클레오티드-결합 단백질 1 (D6RD60), S100A9 (S10A9), S100A8 (S10A8), 갈렉틴-3-결합 단백질 (LG3BP), Ig 알파-1 쇄 C 영역의 클러스터 (IGHA1), Ig 카파 쇄 V-III 영역 HAH의 클러스터 (KV312), VEGF 공조절형 케모카인 1 (VCC1), L-락테이트 데히드로게나제 A 쇄 (LDHA), 알도-케토리덕타제 패밀리 1 구성원 C (AKR1C1), 루트레틴 (B1AKD8), L-락테이트 데히드로게나제 B 쇄 (LDHB), 망막 데히드로게나제 1 (AL1A1), 미규명 단백질 (B4E1Z4), 알파-1-항키모트립신 (AACT), 슈퍼옥시드 디스뮤타제 [Cu-Zn] (SODC), SPARC-유사 단백질 1 (SPRL1), Ig 중쇄 V-III 영역 TIL (HV304), 케라틴 (K1C9), 시스타틴-SN (CYTN), 알파-악티닌-4 (ACTN4), Ig 람다-3 쇄 C 영역 (단편) (IGLC3), 면역글로불린 람다-유사 폴리펩티드 5 (IGLL5), 알콜 데히드로게나제 1C (ADHIG), 말레이트 데히드로게나제, 미토콘드리아 (MDHM), 칼모듈린-유사 단백질 5 (CALL5), 알파-1-항트립신 (A1AT), 알파-1B-당단백질 (A1BG), 류신이 풍부한 알파-2-당단백질 (A2GL), 소형 유비퀴틴-관련 변형인자 3 (A8MU27), 앞 구배 단백질 2 동족체 (AGR2), 프로필린-1, (PROF1), Ig 람다 쇄 V-III 영역 LOI의 클러스터 (LV302), 프로트롬빈 (E9PIT3), 헤모펙신 (HEMO), Ig 감마-2 쇄 C 영역 (IGHG2), 유비퀴틴-40S 리보솜 단백질 S27a (RPS27A), 아파민 (AFAM), 아포지질단백질 A-I (APOA1), 아포지질단백질 A-IV (APOA4), 플라빈 리덕타제 (NADPH)(BLVRB), 프로사포신 (PSAP), 라크리틴 (LACRT), 60S 산성 리보솜 단백질 P1 (RLA1), 인터-알파-트립신 억제제 중쇄 H2 (ITIH2), 뮤신-유사 단백질 1 (MUCL1), S100 A6 (S100A6), Na(+)/H(+) 교환 조절 보조인자 NHE-RF1 (NHRF1), 티오레독신 도메인-함유 단백질 17 (I3L0K2), 림프구-특이 단백질 (LSP1), 합토글로빈의 클러스터 (H3BS21), 미오신 조절 경쇄 12A (J2QRS3), 리보뉴클레아제 억제제 (RINI), 알파-에놀라제 (ENOA), Ig 카파 쇄 V-I 영역 EU의 클러스터 (KV106), 알콜 데히드로게나제 부류 4 뮤/시그마 쇄 (ADH7), 단백질 AMBP (AMBP), 안지오텐시노겐 (ANGT), 항트롬빈-III (ANT3), 아포지질단백질 A-II (APOA2), 칼페스타틴 (B7Z574), 뇌 산성 가용성 단백질 1 (BASP1), 알파-2-HS-당단백질 (C9JV77), 칼레티쿨린 (CALR), 칼페인-1 촉매성 서브유니트 (CAN1), 세포 분열 조절 단백질 42 동족체 (CDC42), 보체 C3 (CO3), 코로닌-1A (COR1A), 프로그램화된 세포 사멸 6-상호작용 단백질 (DCD), 데핀신 1 (DEF1), F-박스 유일 단백질 50 (FBX50), 감마-글루타밀시클로트랜스퍼라제 (GGCT), 글루타티온 리덕타제, 미토콘드리아 (GSHR), 케라틴, II형 세포골격 1 (K2C1), UMP-CMP 키나제 (KCY), 메소텔린 (MSLN), N-아세틸무라모일-L-알라닌 아미다제 (PGRP2), 니코티네이트 포스포리보실트랜스퍼라제 (PNCB), 인터-알파-트립신 억제제 중쇄 H1 (ITIH1), 리보뉴클레아제 T2 (RNASET2), 슈퍼옥시드 디스뮤타제 [Mn], 미토콘드리아 (SODM), 소형 프롤린이 풍부한 단백질 3 (SPRR3), Src 기질 코탁틴 (SRC8), 튜뷸린 베타-4B 쇄의 클러스터 (TBB4B), 트로포미오신 알파-3 쇄 (TPM3), 세로트랜스페린 (TRFE), 글루타티온 S-트랜스퍼라제 P (THIO), 비트로넥틴 (VTNC), 비타민 D 결합 단백질 (Q6LDC6), 인터-알파-트립신 억제제 중쇄 H4 (ITIH4), 메탈로프로테아제 억제제 (TIMP1), 열 쇼크 단백질 90 (HSP90), 카텝신 B (CATB), 셀룰로플라즈민 (CERU), 칼프로텍틴, 14-3-3 시그마 (1433S), 알파-2-hs-당단백질 (FETUA), 알파-2-마크로글로불린 (A2MG), 트랜스티레틴 (TTHY)은 결합제, 예를 들어, 항체, 펩토이드, 또는 코팅된 표면, 및 상기 단백질에 특이적인 결합 상호작용을 제공하여 검출가능한 신호, 예컨대, 형광, 변색, 또는 UV 흡광도 발생에 기초하여 정량화될 수 있는 반응이 일어나도록 하는 시약을 공급함으로써 검출될 수 있다. 카트리지 중의 상기 성분을 파트너링 판독 기계, 예컨대, 현장 진단시 사용될 수 있는 현장 진단 장치에 공급하는 것 또한 제공한다. 상기 단백질 및 폴리펩티드에 대한 결합제 또한 측면 유동 장치에서의 검출을 위해 사용될 수 있다. 따라서, 결합 파트너, 예컨대, 항체를 사용하여 샘플 중의 단백질의 발현 수준을 검출하는 방법을 사용하여 면역검정법으로 본원에서 제공하는 마커를 검출할 수 있다.
면역검정법은 전형적으로 바이오마커에 특이적으로 결합하거나, 또는 다르게는 그를 인식하는 항체 또는 항원과 시험 샘플을 접촉시키고, 샘플 중의 바이오마커에 결합된 항체 또는 항원의 복합체의 존재를 검출하는 것을 포함한다. 면역검정 방법은 효소 결합 면역흡착 검정법 (ELISA), 방사성면역검정법 (RIA), 및 웨스턴 블롯을 비롯한, 항체/항원 복합체 인식, 및 수개의 원하는 항체가 지지체, 예컨대, 유리 비드 또는 플레이트 상에 배치되어 있고, 시험 샘플과 반응하거나, 또는 다르게는 그와 접촉하게 되는 항체 어레이 사용을 비롯한, 다중 검정법 사용을 포함하는, 당업계에 공지된 매우 다양한 면역검정 방법으로부터 선택될 수 있다. 예컨대, 검정법은 당업자에게 널리 공지되어 있다.
샘플 중의 본원에 기술된 바이오마커의 검출은 다양한 방식으로 수행될 수 있다. 한 실시양태에서, 본 방법은 샘플로부터 수득된 mRNA로부터의 상보적 DNA의 역전사를 제공한다. 형광 염료로 표지된 상보적 RNA는 상보적 DNA로 전사될 수 있고, 이어서, 올리고뉴클레오티드 프로브로 이루어진 어레이에 하이브리드화된다. 하이브리드화에 의해 발생된 형광색은 기계, 예컨대, 슈어스캔(SureScan) 마이크로어레이 스캐너 (애질런트 테크놀러지즈(Agilent Technologies))에 의해 판독할 수 있고, 데이터를 수득하고, 소프트웨어, 예컨대, 애질런트 피쳐 엑스트렉션 소프트웨어(Agilent Feature Extraction Software) (9.1)를 이용하여 프로세싱할 수 있다. 상기 어레이 기반 방법은 유전자 발현 프로파일을 밝히는 마이크로어레이 분석을 포함한다. 본원에서 사용되는 바, "유전자 발현 프로파일"이라는 용어는 대상체에서의 유전자 패널의 mRNA 또는 단백질의 발현 수준을 의미한다. 본원에서 사용되는 바, "진단 패널"이라는 용어는 질환 상태를 진단하거나, 예측하는 데 의존할 수 있는 발현 수준을 가지는 유전자, 펩티드 또는 단백질 패널을 의미한다. 상기 패널에는 본원에서 제공되는 바와 같은, 하기로부터 선택되고, 표 1에 열거된 유전자, 펩티드 및 단백질: Ig 람다 쇄 V-IV 영역 Hil (LV403), Ig 중쇄 V-III BRO (HV305), Ig 중쇄 V-III VH26 (HV303), β-2-마이크로글로불린 (B2MG), 리포칼린-1 (LCN1), 아연-α-2-당단백질 (ZA2G), 시스타틴 B (CYTB), 항류코프로테이나제 (SLP1), 갈렉틴-3 (LEG3), 히스티딘 트리아드 뉴클레오티드-결합 단백질 1 (D6RD60), S100A9 (S10A9), S100A8 (S10A8), 갈렉틴-3-결합 단백질 (LG3BP), Ig 알파-1 쇄 C 영역의 클러스터 (IGHA1), Ig 카파 쇄 V-III 영역 HAH의 클러스터 (KV312), VEGF 공조절형 케모카인 1 (VCC1), L-락테이트 데히드로게나제 A 쇄 (LDHA), 알도-케토리덕타제 패밀리 1 구성원 C (AKR1C1), 루트레틴 (B1AKD8), L-락테이트 데히드로게나제 B 쇄 (LDHB), 망막 데히드로게나제 1 (AL1A1), 미규명 단백질 (B4E1Z4), 알파-1-항키모트립신 (AACT), 슈퍼옥시드 디스뮤타제 [Cu-Zn] (SODC), SPARC-유사 단백질 1 (SPRL1), Ig 중쇄 V-III 영역 TIL (HV304), 케라틴 (K1C9), 시스타틴-SN (CYTN), 알파-악티닌-4 (ACTN4), Ig 람다-3 쇄 C 영역 (단편) (IGLC3), 면역글로불린 람다-유사 폴리펩티드 5 (IGLL5), 알콜 데히드로게나제 1C (ADHIG), 말레이트 데히드로게나제, 미토콘드리아 (MDHM), 칼모듈린-유사 단백질 5 (CALL5), 알파-1-항트립신 (A1AT), 알파-1B-당단백질 (A1BG), 류신이 풍부한 알파-2-당단백질 (A2GL), 소형 유비퀴틴-관련 변형인자 3 (A8MU27), 앞 구배 단백질 2 동족체 (AGR2), 프로필린-1 (PROF1), Ig 람다 쇄 V-III 영역 LOI의 클러스터 (LV302), 프로트롬빈 (E9PIT3), 헤모펙신 (HEMO), Ig 감마-2 쇄 C 영역 (IGHG2), 유비퀴틴-40S 리보솜 단백질 S27a (RPS27A), 아파민 (AFAM), 아포지질단백질 A-I (APOA1), 아포지질단백질 A-IV (APOA4), 플라빈 리덕타제 (NADPH)(BLVRB), 프로사포신 (PSAP), 라크리틴 (LACRT), 60S 산성 리보솜 단백질 P1 (RLA1), 인터-알파-트립신 억제제 중쇄 H2 (ITIH2), 뮤신-유사 단백질 1 (MUCL1), S100 A6 (S100A6), Na(+)/H(+) 교환 조절 보조인자 NHE-RF1 (NHRF1), 티오레독신 도메인-함유 단백질 17 (I3L0K2), 림프구-특이 단백질 (LSP1), 합토글로빈의 클러스터 (H3BS21), 미오신 조절 경쇄 12A (J2QRS3), 리보뉴클레아제 억제제 (RINI), 알파-에놀라제 (ENOA), Ig 카파 쇄 V-I 영역 EU의 클러스터 (KV106), 알콜 데히드로게나제 부류 4 뮤/시그마 쇄 (ADH7), 단백질 AMBP (AMBP), 안지오텐시노겐 (ANGT), 항트롬빈-III (ANT3), 아포지질단백질 A-II (APOA2), 칼페스타틴 (B7Z574), 뇌 산성 가용성 단백질 1 (BASP1), 알파-2-HS-당단백질 (C9JV77), 칼레티쿨린 (CALR), 칼페인-1 촉매성 서브유니트 (CAN1), 세포 분열 조절 단백질 42 동족체 (CDC42), 보체 C3 (CO3), 코로닌-1A (COR1A), 프로그램화된 세포 사멸 6-상호작용 단백질 (DCD), 데핀신 1 (DEF1), F-박스 유일 단백질 50 (FBX50), 감마-글루타밀시클로트랜스퍼라제 (GGCT), 글루타티온 리덕타제, 미토콘드리아 (GSHR), 케라틴, II형 세포골격 1 (K2C1), UMP-CMP 키나제 (KCY), 메소텔린 (MSLN), N-아세틸무라모일-L-알라닌 아미다제 (PGRP2), 니코티네이트 포스포리보실트랜스퍼라제 (PNCB), 인터-알파-트립신 억제제 중쇄 H1 (ITIH1), 리보뉴클레아제 T2 (RNASET2), 슈퍼옥시드 디스뮤타제 [Mn], 미토콘드리아 (SODM), 소형 프롤린이 풍부한 단백질 3 (SPRR3), Src 기질 코탁틴 (SRC8), 튜뷸린 베타-4B 쇄의 클러스터 (TBB4B), 트로포미오신 알파-3 쇄 (TPM3), 세로트랜스페린 (TRFE), 글루타티온 S-트랜스퍼라제 P (THIO), 비트로넥틴 (VTNC), 비타민 D 결합 단백질 (Q6LDC6), 인터-알파-트립신 억제제 중쇄 H4 (ITIH4), 메탈로프로테아제 억제제 (TIMP1), 열 쇼크 단백질 90 (HSP90), 카텝신 B (CATB), 셀룰로플라즈민 (CERU), 칼프로텍틴, 14-3-3 시그마 (1433S), 알파-2-hs-당단백질 (FETUA), 알파-2-마크로글로불린 (A2MG), 트랜스티레틴 (TTHY) 뿐만 아니라, 그의 임의 조합이 포함된다.
다른 실시양태에서, 상보적 DNA는 샘플로부터 수득된 mRNA로부터 역전사되고, 증폭되고, 실시간 PCR에 의해 동시에 정량화됨으로써 상보적 DNA 샘플 뿐만 아니라, 원래의 mRNA 샘플 중의 특이 유전자 생성물을 검출 및 정량화 (DNA 입력량 또는 추가의 정규화 유전자로 정규화되었을 때, 절대 카피수 또는 상대량으로서 정량화), 둘 모두를 수행할 수 있다.
본 발명의 방법 버전은 적어도 1개의 바이오마커를 검출하는 단계를 포함한다. 그러나, 임의 개수의 바이오마커가 검출될 수 있다. 분석으로 적어도 2개의 바이오마커가 검출되는 것이 바람직하다. 그러나, 본원에 기술된 바이오마커 중 3개, 4개 이상 (그 모두 포함)의 바이오마커가 분석에서 사용될 수 있다는 것도 이해할 것이다. 따라서, 적어도 하나의 마커가 검출될 수 있을 뿐만 아니라, 임의 개수의 마커 또는 그의 조합도 검출에서 사용될 수 있다. 추가로, 본원에 기술되지 않은 다른 바이오마커는 암 진단을 지원하기 위해서 본원에서 개시된 바이오마커 중 임의의 것과 조합될 수 있다. 또한, 상기 바이오마커의 임의 조합은 본 발명의 버전에 따라 검출될 수 있다.
하기로부터 선택되고, 표 1에 열거된 마커: Ig 람다 쇄 V-IV 영역 Hil (LV403), Ig 중쇄 V-III BRO (HV305), Ig 중쇄 V-III VH26 (HV303), β-2-마이크로글로불린 (B2MG), 리포칼린-1 (LCN1), 아연-α-2-당단백질 (ZA2G), 시스타틴 B (CYTB), 항류코프로테이나제 (SLP1), 갈렉틴-3 (LEG3), 히스티딘 트리아드 뉴클레오티드-결합 단백질 1 (D6RD60), S100A9 (S10A9), S100A8 (S10A8), 갈렉틴-3-결합 단백질 (LG3BP), Ig 알파-1 쇄 C 영역의 클러스터 (IGHA1), Ig 카파 쇄 V-III 영역 HAH의 클러스터 (KV312), VEGF 공조절형 케모카인 1 (VCC1), L-락테이트 데히드로게나제 A 쇄 (LDHA), 알도-케토리덕타제 패밀리 1 구성원 C (AKR1C1), 루트레틴 (B1AKD8), L-락테이트 데히드로게나제 B 쇄 (LDHB), 망막 데히드로게나제 1 (AL1A1), 미규명 단백질 (B4E1Z4), 알파-1-항키모트립신 (AACT), 슈퍼옥시드 디스뮤타제 [Cu-Zn] (SODC), SPARC-유사 단백질 1 (SPRL1), Ig 중쇄 V-III 영역 TIL (HV304), 케라틴 (K1C9), 시스타틴-SN (CYTN), 알파-악티닌-4 (ACTN4), Ig 람다-3 쇄 C 영역 (단편) (IGLC3), 면역글로불린 람다-유사 폴리펩티드 5 (IGLL5), 알콜 데히드로게나제 1C (ADHIG), 말레이트 데히드로게나제, 미토콘드리아 (MDHM), 칼모듈린-유사 단백질 5 (CALL5), 알파-1-항트립신 (A1AT), 알파-1B-당단백질 (A1BG), 류신이 풍부한 알파-2-당단백질 (A2GL), 소형 유비퀴틴-관련 변형인자 3 (A8MU27), 앞 구배 단백질 2 동족체 (AGR2), 프로필린-1 (PROF1), Ig 람다 쇄 V-III 영역 LOI의 클러스터 (LV302), 프로트롬빈 (E9PIT3), 헤모펙신 (HEMO), Ig 감마-2 쇄 C 영역 (IGHG2), 유비퀴틴-40S 리보솜 단백질 S27a (RPS27A), 아파민 (AFAM), 아포지질단백질 A-I (APOA1), 아포지질단백질 A-IV (APOA4), 플라빈 리덕타제 (NADPH)(BLVRB), 프로사포신 (PSAP), 라크리틴 (LACRT), 60S 산성 리보솜 단백질 P1 (RLA1), 인터-알파-트립신 억제제 중쇄 H2 (ITIH2), 뮤신-유사 단백질 1 (MUCL1), S100 A6 (S100A6), Na(+)/H(+) 교환 조절 보조인자 NHE-RF1 (NHRF1), 티오레독신 도메인-함유 단백질 17 (I3L0K2), 림프구-특이 단백질 (LSP1), 합토글로빈의 클러스터 (H3BS21), 미오신 조절 경쇄 12A (J2QRS3), 리보뉴클레아제 억제제 (RINI), 알파-에놀라제 (ENOA), Ig 카파 쇄 V-I 영역 EU의 클러스터 (KV106), 알콜 데히드로게나제 부류 4 뮤/시그마 쇄 (ADH7), 단백질 AMBP (AMBP), 안지오텐시노겐 (ANGT), 항트롬빈-III (ANT3), 아포지질단백질 A-II (APOA2), 칼페스타틴 (B7Z574), 뇌 산성 가용성 단백질 1 (BASP1), 알파-2-HS-당단백질 (C9JV77), 칼레티쿨린 (CALR), 칼페인-1 촉매성 서브유니트 (CAN1), 세포 분열 조절 단백질 42 동족체 (CDC42), 보체 C3 (CO3), 코로닌-1A (COR1A), 프로그램화된 세포 사멸 6-상호작용 단백질 (DCD), 데핀신 1 (DEF1), F-박스 유일 단백질 50 (FBX50), 감마-글루타밀시클로트랜스퍼라제 (GGCT), 글루타티온 리덕타제, 미토콘드리아 (GSHR), 케라틴, II형 세포골격 1 (K2C1), UMP-CMP 키나제 (KCY), 메소텔린 (MSLN), N-아세틸무라모일-L-알라닌 아미다제 (PGRP2), 니코티네이트 포스포리보실트랜스퍼라제 (PNCB), 인터-알파-트립신 억제제 중쇄 H1 (ITIH1), 리보뉴클레아제 T2 (RNASET2), 슈퍼옥시드 디스뮤타제 [Mn], 미토콘드리아 (SODM), 소형 프롤린이 풍부한 단백질 3 (SPRR3), Src 기질 코탁틴 (SRC8), 튜뷸린 베타-4B 쇄의 클러스터 (TBB4B), 트로포미오신 알파-3 쇄 (TPM3), 세로트랜스페린 (TRFE), 글루타티온 S-트랜스퍼라제 P (THIO), 비트로넥틴 (VTNC), 비타민 D 결합 단백질 (Q6LDC6), 인터-알파-트립신 억제제 중쇄 H4 (ITIH4), 메탈로프로테아제 억제제 (TIMP1), 열 쇼크 단백질 90 (HSP90), 카텝신 B (CATB), 셀룰로플라즈민 (CERU), 칼프로텍틴, 14-3-3 시그마 (1433S), 알파-2-hs-당단백질 (FETUA), 알파-2-마크로글로불린 (A2MG), 트랜스티레틴 (TTHY)은 대조군 샘플 중의 해당 마커 수준과 비교하여 적어도 1.5배, 2배, 4배, 5배, 8배, 10배 이상 증가 또는 감소될 수 있다. 대조군 샘플은 암 결여 대상체로부터의 샘플, 암 결여 대상체로부터의 풀링된 샘플일 수 있거나, 또는 암 결여 대상체의 평균 발현 수준인 것으로 공지되어 있는 대조군 또는 기준선 발현 수준일 수 있다.
본 개시내용 전역에 걸쳐 수개의 용어가 사용되며, 이는 당업계에서 통상 사용되는 바와 같이, 또는 본원에서 구체적으로 제공되는 바와 같이 정의되어야 한다. 본원에서 제공되는 바, 질량 분석법 또는 MS은 펩티드 서열 및 화학 구조를 확인하거나, 결정하기 위해 전기장 또는 자기장을 발생시켜 펩티드 및 화학 화합물의 질량 대 전하의 비를 결정하는 분석 기법을 나타낸다. LC-MS/MS 분석법은 고성능 액체 크로마토그래피 (HPLC)의 분리 능력을 질량 분석법의 질량 분석과 조합한 분석 기법을 나타낸다. 삼중 4극 질량 분석법은 3개의 이온화 챔버 (Q1, Q2, & Q3)가 장착된 탠덤 질량 분석기를 나타낸다. 이 기법을 통해 관심의 대상이 되는 분자를 표적 검출할 수 있다. 이온 쌍이란 Q1에서 그의 이중 또는 삼중으로 하전된 형태로 검출된 모체 펩티드, 및 삼중 4극 질량 분석 장치의 Q2에 의해 발생되고, Q3에서 검출되는 생성된 y 또는 b 이온을 나타낸다. SIS 내부 펩티드는 Q1에서 모니터링되고, 관심의 대상이 되는 펩티드를 정량화하기 위한 내부 표준 참조로서 사용되는 펩티드와 동일한 서열을 가지는, 합성된 동위원소로 표지된 펩티드를 나타낸다. -y 이온은 펩티드 단편의 c 말단으로부터 발생된 이온을 나타낸다. -b 이온은 펩티드 단편의 n 말단으로부터 발생된 이온을 나타낸다. 정량 이온은 생물학적 샘플 중 그의 모체 단백질의 정량을 결정하는 데 사용되는, 선택된 최고 강도의 y 또는 b 이온을 나타낸다. 정성 이온은 관심의 대상이 되는 선택된 단백질로의 정성 이온의, 및 선택된 표준으로의 표지된 펩티드의 통합성을 확실히 하기 위해 선택된 이온/이온들을 나타낸다.
CLIA란, 임상 시험 및 기초 연구를 제외한, 미국 내에서 인간에게서 미리 형성되는 모든 임상 실험실 검사에 적용되는 연방 정부 규제 표준인 임상 실험 개선 개정(Clinical Laboratory Improvements Amendments)을 나타낸다 (문헌 [CLIA related Federal Register and Code of Federal Regulation Announcements]). CLIA 승인 실험실이란, 질환 또는 장애의 진단, 예방 또는 치료를 위해 인간 표본에 대하여 실험실 검사를 미리 형성하고, 미국 식품 의약국(Food and Drug Administration: FDA) 승인 규제 기관에 의해 승인을 받고, 그에 의해 감시를 받는 임상 실험실을 의미한다 (문헌 [CLIA Laws and Regulations, 2013]). CLIA-보류 시험이란 FDA에 의해 정의된, 위험, 오류, 및 복잡성에 관한 구체적인 기준을 충족시키는 임상 실험실 시험을 의미한다.
현장 진단 장치란, 관심의 대상이 되는 바이오마커, 또는 일련의 바이오마커에 대한 결합제를 함유하며, 검출된 바이오마커의 존재, 부재, 및 일부 경우에서는 그의 농도에 관한 정보를 생성할 수 있는 것인, 환자 및 의사 치료 위치에서 이용가능한 계기 또는 카트리지를 의미한다. 분석물이란 임의의 측정가능한 바이오마커를 의미하며, 이는 단백질, 펩티드, 거대분자, 대사산물, 소분자, 또는 자기항체일 수 있다. 본원에서 사용되는 바, 생물학적 유체란 눈물, 전혈, 혈청, 뇨, 및 타액을 의미한다. 바이오마커란 질환 또는 병태의 결과로서 체내에서 그의 농도 수준이 변하는, 예를 들어, 증가 또는 감소하는 것인, 임의의 물질 (예컨대, 단백질, 펩티드, 대사산물, 폴리뉴클레오티드 서열)을 의미한다.
측면 유동 검사란 장치가 소결된 중합체로 이루어진 다공지를 사용하여 생물학적 유체 중 분석물의 존재를 측정하는 것을 나타낸다. ELISA란, 항체 또는 항원을 이용하여 관심 분석물의 존재 및 농도를 검출하는, 효소 결합 면역흡착 검정법을 의미한다. 진단 패널이란, 그의 조합된 농도가 질환 상태, 예를 들어, 암을 진단하는 데 사용되는 것인, 분자, 예를 들어, 단백질 또는 펩티드로 이루어진 군을 의미한다. 유방암 마커란, 암의 존재 또는 부재의 결과로서 체내에서 그의 농도 수준이 변하는: 예를 들어, 증가 또는 감소하는 것인, 분자: 예를 들어, 단백질, 펩티드, 대사산물, 폴리뉴클레오티드 서열을 의미한다.
대상체에서 암, 및 특히, 유방암을 진단하는 데 유용한 것 이외에도, 본원에서 제공하는 키트 및 방법은 이미 암 진단을 받은 개체에서 암의 치료 또는 재발을 모니터링하는 데에도 사용될 수 있다. 따라서, 하기로부터 선택되고, 표 1에 열거된 마커: Ig 람다 쇄 V-IV 영역 Hil (LV403), Ig 중쇄 V-III BRO (HV305), Ig 중쇄 V-III VH26 (HV303), β-2-마이크로글로불린 (B2MG), 리포칼린-1 (LCN1), 아연-α-2-당단백질 (ZA2G), 시스타틴 B (CYTB), 항류코프로테이나제 (SLP1), 갈렉틴-3 (LEG3), 히스티딘 트리아드 뉴클레오티드-결합 단백질 1 (D6RD60), S100A9 (S10A9), S100A8 (S10A8), 갈렉틴-3-결합 단백질 (LG3BP), Ig 알파-1 쇄 C 영역의 클러스터 (IGHA1), Ig 카파 쇄 V-III 영역 HAH의 클러스터 (KV312), VEGF 공조절형 케모카인 1 (VCC1), L-락테이트 데히드로게나제 A 쇄 (LDHA), 알도-케토리덕타제 패밀리 1 구성원 C (AKR1C1), 루트레틴 (B1AKD8), L-락테이트 데히드로게나제 B 쇄 (LDHB), 망막 데히드로게나제 1 (AL1A1), 미규명 단백질 (B4E1Z4), 알파-1-항키모트립신 (AACT), 슈퍼옥시드 디스뮤타제 [Cu-Zn] (SODC), SPARC-유사 단백질 1 (SPRL1), Ig 중쇄 V-III 영역 TIL (HV304), 케라틴 (K1C9), 시스타틴-SN (CYTN), 알파-악티닌-4 (ACTN4), Ig 람다-3 쇄 C 영역 (단편) (IGLC3), 면역글로불린 람다-유사 폴리펩티드 5 (IGLL5), 알콜 데히드로게나제 1C (ADHIG), 말레이트 데히드로게나제, 미토콘드리아 (MDHM), 칼모듈린-유사 단백질 5 (CALL5), 알파-1-항트립신 (A1AT), 알파-1B-당단백질 (A1BG), 류신이 풍부한 알파-2-당단백질 (A2GL), 소형 유비퀴틴-관련 변형인자 3 (A8MU27), 앞 구배 단백질 2 동족체 (AGR2), 프로필린-1 (PROF1), Ig 람다 쇄 V-III 영역 LOI의 클러스터 (LV302), 프로트롬빈 (E9PIT3), 헤모펙신 (HEMO), Ig 감마-2 쇄 C 영역 (IGHG2), 유비퀴틴-40S 리보솜 단백질 S27a (RPS27A), 아파민 (AFAM), 아포지질단백질 A-I (APOA1), 아포지질단백질 A-IV (APOA4), 플라빈 리덕타제 (NADPH)(BLVRB), 프로사포신 (PSAP), 라크리틴 (LACRT), 60S 산성 리보솜 단백질 P1 (RLA1), 인터-알파-트립신 억제제 중쇄 H2 (ITIH2), 뮤신-유사 단백질 1 (MUCL1), S100 A6 (S100A6), Na(+)/H(+) 교환 조절 보조인자 NHE-RF1 (NHRF1), 티오레독신 도메인-함유 단백질 17 (I3L0K2), 림프구-특이 단백질 (LSP1), 합토글로빈의 클러스터 (H3BS21), 미오신 조절 경쇄 12A (J2QRS3), 리보뉴클레아제 억제제 (RINI), 알파-에놀라제 (ENOA), Ig 카파 쇄 V-I 영역 EU의 클러스터 (KV106), 알콜 데히드로게나제 부류 4 뮤/시그마 쇄 (ADH7), 단백질 AMBP (AMBP), 안지오텐시노겐 (ANGT), 항트롬빈-III (ANT3), 아포지질단백질 A-II (APOA2), 칼페스타틴 (B7Z574), 뇌 산성 가용성 단백질 1 (BASP1), 알파-2-HS-당단백질 (C9JV77), 칼레티쿨린 (CALR), 칼페인-1 촉매성 서브유니트 (CAN1), 세포 분열 조절 단백질 42 동족체 (CDC42), 보체 C3 (CO3), 코로닌-1A (COR1A), 프로그램화된 세포 사멸 6-상호작용 단백질 (DCD), 데핀신 1 (DEF1), F-박스 유일 단백질 50 (FBX50), 감마-글루타밀시클로트랜스퍼라제 (GGCT), 글루타티온 리덕타제, 미토콘드리아 (GSHR), 케라틴, II형 세포골격 1 (K2C1), UMP-CMP 키나제 (KCY), 메소텔린 (MSLN), N-아세틸무라모일-L-알라닌 아미다제 (PGRP2), 니코티네이트 포스포리보실트랜스퍼라제 (PNCB), 인터-알파-트립신 억제제 중쇄 H1 (ITIH1), 리보뉴클레아제 T2 (RNASET2), 슈퍼옥시드 디스뮤타제 [Mn], 미토콘드리아 (SODM), 소형 프롤린이 풍부한 단백질 3 (SPRR3), Src 기질 코탁틴 (SRC8), 튜뷸린 베타-4B 쇄의 클러스터 (TBB4B), 트로포미오신 알파-3 쇄 (TPM3), 세로트랜스페린 (TRFE), 글루타티온 S-트랜스퍼라제 P (THIO), 비트로넥틴 (VTNC), 비타민 D 결합 단백질 (Q6LDC6), 인터-알파-트립신 억제제 중쇄 H4 (ITIH4), 메탈로프로테아제 억제제 (TIMP1), 열 쇼크 단백질 90 (HSP90), 카텝신 B (CATB), 셀룰로플라즈민 (CERU), 칼프로텍틴, 14-3-3 시그마 (1433S), 알파-2-hs-당단백질 (FETUA), 알파-2-마크로글로불린 (A2MG), 트랜스티레틴 (TTHY)의 수준이 치료 후 같은 대상체에서 시간이 경과함에 따라 증가 또는 감소하였다면, 암을 표적화하는 추가의 화학요법이 투여될 수 있다.
방법 및 키트는 또한 화학요법 치료의 효능을 모니터링하는 데 사용될 수 있다. 상기 대체 실시양태에서, 대상체에서 어떤 바이오마커(들)가 조사되는지에 따라, 치료 요법이 효과적이라면, 하기로부터 선택되고, 표 1에 열거된 바이오마커: Ig 람다 쇄 V-IV 영역 Hil (LV403), Ig 중쇄 V-III BRO (HV305), Ig 중쇄 V-III VH26 (HV303), β-2-마이크로글로불린 (B2MG), 리포칼린-1 (LCN1), 아연-α-2-당단백질 (ZA2G), 시스타틴 B (CYTB), 항류코프로테이나제 (SLP1), 갈렉틴-3 (LEG3), 히스티딘 트리아드 뉴클레오티드-결합 단백질 1 (D6RD60), S100A9 (S10A9), S100A8 (S10A8), 갈렉틴-3-결합 단백질 (LG3BP), Ig 알파-1 쇄 C 영역의 클러스터 (IGHA1), Ig 카파 쇄 V-III 영역 HAH의 클러스터 (KV312), VEGF 공조절형 케모카인 1 (VCC1), L-락테이트 데히드로게나제 A 쇄 (LDHA), 알도-케토리덕타제 패밀리 1 구성원 C (AKR1C1), 루트레틴 (B1AKD8), L-락테이트 데히드로게나제 B 쇄 (LDHB), 망막 데히드로게나제 1 (AL1A1), 미규명 단백질 (B4E1Z4), 알파-1-항키모트립신 (AACT), 슈퍼옥시드 디스뮤타제 [Cu-Zn] (SODC), SPARC-유사 단백질 1 (SPRL1), Ig 중쇄 V-III 영역 TIL (HV304), 케라틴 (K1C9), 시스타틴-SN (CYTN), 알파-악티닌-4 (ACTN4), Ig 람다-3 쇄 C 영역 (단편) (IGLC3), 면역글로불린 람다-유사 폴리펩티드 5 (IGLL5), 알콜 데히드로게나제 1C (ADHIG), 말레이트 데히드로게나제, 미토콘드리아 (MDHM), 칼모듈린-유사 단백질 5 (CALL5), 알파-1-항트립신 (A1AT), 알파-1B-당단백질 (A1BG), 류신이 풍부한 알파-2-당단백질 (A2GL), 소형 유비퀴틴-관련 변형인자 3 (A8MU27), 앞 구배 단백질 2 동족체 (AGR2), 프로필린-1 (PROF1), Ig 람다 쇄 V-III 영역 LOI의 클러스터 (LV302), 프로트롬빈 (E9PIT3), 헤모펙신 (HEMO), Ig 감마-2 쇄 C 영역 (IGHG2), 유비퀴틴-40S 리보솜 단백질 S27a (RPS27A), 아파민 (AFAM), 아포지질단백질 A-I (APOA1), 아포지질단백질 A-IV (APOA4), 플라빈 리덕타제 (NADPH)(BLVRB), 프로사포신 (PSAP), 라크리틴 (LACRT), 60S 산성 리보솜 단백질 P1 (RLA1), 인터-알파-트립신 억제제 중쇄 H2 (ITIH2), 뮤신-유사 단백질 1 (MUCL1), S100 A6 (S100A6), Na(+)/H(+) 교환 조절 보조인자 NHE-RF1 (NHRF1), 티오레독신 도메인-함유 단백질 17 (I3L0K2), 림프구-특이 단백질 (LSP1), 합토글로빈의 클러스터 (H3BS21), 미오신 조절 경쇄 12A (J2QRS3), 리보뉴클레아제 억제제 (RINI), 알파-에놀라제 (ENOA), Ig 카파 쇄 V-I 영역 EU의 클러스터 (KV106), 알콜 데히드로게나제 부류 4 뮤/시그마 쇄 (ADH7), 단백질 AMBP (AMBP), 안지오텐시노겐 (ANGT), 항트롬빈-III (ANT3), 아포지질단백질 A-II (APOA2), 칼페스타틴 (B7Z574), 뇌 산성 가용성 단백질 1 (BASP1), 알파-2-HS-당단백질 (C9JV77), 칼레티쿨린 (CALR), 칼페인-1 촉매성 서브유니트 (CAN1), 세포 분열 조절 단백질 42 동족체 (CDC42), 보체 C3 (CO3), 코로닌-1A (COR1A), 프로그램화된 세포 사멸 6-상호작용 단백질 (DCD), 데핀신 1 (DEF1), F-박스 유일 단백질 50 (FBX50), 감마-글루타밀시클로트랜스퍼라제 (GGCT), 글루타티온 리덕타제, 미토콘드리아 (GSHR), 케라틴, II형 세포골격 1 (K2C1), UMP-CMP 키나제 (KCY), 메소텔린 (MSLN), N-아세틸무라모일-L-알라닌 아미다제 (PGRP2), 니코티네이트 포스포리보실트랜스퍼라제 (PNCB), 인터-알파-트립신 억제제 중쇄 H1 (ITIH1), 리보뉴클레아제 T2 (RNASET2), 슈퍼옥시드 디스뮤타제 [Mn], 미토콘드리아 (SODM), 소형 프롤린이 풍부한 단백질 3 (SPRR3), Src 기질 코탁틴 (SRC8), 튜뷸린 베타-4B 쇄의 클러스터 (TBB4B), 트로포미오신 알파-3 쇄 (TPM3), 세로트랜스페린 (TRFE), 글루타티온 S-트랜스퍼라제 P (THIO), 비트로넥틴 (VTNC), 비타민 D 결합 단백질 (Q6LDC6), 인터-알파-트립신 억제제 중쇄 H4 (ITIH4), 메탈로프로테아제 억제제 (TIMP1), 열 쇼크 단백질 90 (HSP90), 카텝신 B (CATB), 셀룰로플라즈민 (CERU), 칼프로텍틴, 14-3-3 시그마 (1433S), 알파-2-hs-당단백질 (FETUA), 알파-2-마크로글로불린 (A2MG), 트랜스티레틴 (TTHY)의 수준은 시간이 경과함에 따라 증가 또는 감소될 수 있고, 치료 요법이 단일 대상체에서 효과가 없다면, 이는 변함이 없거나, 또는 증가 또는 감소될 수 있다.
암을 치료하는 것은 대상체에서 암 세포의 개수, 또는 종양 또는 종괴의 크기를 축소시키거나, 암의 진행을 덜 침습성인 형태로 감소시키거나, 또는 암 세포의 증식을 감소시키거나, 또는 종양의 성장 속도를 감속시키거나, 암 세포를 사멸시키거나, 암 세포의 전이를 감소시키거나, 대상체에서 암이 재발할 가능성을 감소시키는 것을 포함하나, 이에 한정되지 않는다. 본원에서 사용되는 바, 대상체를 치료한다는 것은 임의 유형의 치료가 질환을 갖거나, 또는 그 질환이 발생할 위험이 있는 대상체에게 도움을 준다는 것을 의미하는 것으로, 이는 대상체의 병태, 예를 들어, 하나 이상의 증상의 호전, 질환 진행의 지연, 증상 발병의 지연, 또는 증상 진행의 지연 등을 포함한다.
본 개시내용은 본원에서 기술된 구성, 성분의 배열, 또는 방법 단계의 특정의 상세 내용으로 한정되지 않는다. 본원에서 개시된 조성물 및 방법은 하기 본 개시내용에 비추어 당업자에게 자명하게 되는 각종 방식으로 실시, 사용, 수행 및/또는 형성될 수 있다. 본원에서 사용된 어구 및 용어는 단지 설명 목적으로 사용된 것이며, 본 청구범위의 범주를 한정하는 것으로 간주되지 않아야 한다. 다양한 구조 또는 방법 단계를 언급하기 위해 설명 및 청구범위에서 사용된, 예컨대, 제1, 제2 및 제3과 같은 서수 표기는 임의의 특정 구조 또는 단계, 또는 상기 구조 또는 단계로의 특정 순서 또는 설정을 명시하는 것으로 해석되지 않아야 한다. 본원에 기술된 모든 방법은 본원에서 달리 명시되지 않는 한, 또는 분명하게 맥락상 모순되지 않는 한, 임의의 적합한 순서로 수행될 수 있다. 본원에서 제공하는 임의의 및 모든 예, 또는 예를 들어, "예컨대"와 같은 예시적인 표현을 사용하는 것은 단지 본 개시내용을 용이하게 하기 위한 것으로 의도되며, 달리 주장되지 않는 한, 본 개시내용의 범주를 한정하는 것을 암시하지는 않는다. 본 명세서 중의 어떤 표현도, 본 도면에 제시된 어떤 구조도 주장되지 않은 임의의 요소가 개시된 주제에 필수적인 것임을 명시하는 것으로 해석되어야 한다. 본원에서 "비롯한," "포함하는," 또는 "가지는"이라는 용어, 및 그의 파생어를 사용하는 것은 이하 열거되는 요소 및 그의 등가물을 포함하는 것으로 의도된다. 특정 실시양태를 "비롯한," "포함하는," 또는 "가지는" 것으로 언급된 실시양태는 또한 그 특정 요소로 "본질적으로 이루어진" 및 그로 "이루어진" 것으로 고려된다.
본원에서 달리 명시되지 않는 한, 본원에서 값을 범위로 언급하는 것은 단지 상기 범위 내에 포함된 각각의 별개의 값을 개별적으로 언급하는 약식 방법으로서의 역할을 하는 것으로 의도될 뿐이며, 각각의 별개의 값은 마치 그가 본원에서 개별적으로 언급된 것처럼 명세서에 포함된다. 예를 들어, 농도 범위가 1% 내지 50%인 것으로 언급되었다면, 예컨대, 2% 내지 40%, 10% 내지 30%, 또는 1% 내지 3% 등과 같은 값이 본 명세서에서 명백하게 열거된 것으로 의도된다. 이는 단지 구체적으로 의도되는 것의 예일 뿐이며, 열거된 최저 값과 최고 값 사이의 수치 값과, 그 최저 값 및 최고 값을 포함하는 수치 값의 모든 가능한 조합이 본 개시내용에서 명백하게 언급된 것으로 간주되는 것으로 한다. 특정의 언급된 양 또는 양의 범위를 기술하기 위해 "약"이라는 단어를 사용하는 것은 언급된 양에 근접한 값, 예컨대, 제조 허용 오차(manufacturing tolerance), 측정시 계기 오차 및 인적 오류 등에 기인할 수 있거나, 또는 당연히 그가 원인이 될 수 있는 값이 상기 양에 포함된다는 것을 나타내는 것으로 의도된다. 양을 나타내는 모든 백분율(%)은 달리 명시되지 않는 중량%이다.
본 명세서에서 인용된 임의의 비특허 또는 특허 문헌을 비롯한, 임의의 참고 문헌이 선행 기술로 간주된다는 것을 인정하는 것은 아니다. 특히, 달리 언급하지 않는 한, 본원에서 임의의 문헌을 언급하는 것이 상기 문헌 중 임의의 것이 미국 또는 임의의 다른 국가에서 당업계의 통상의 일반 지식의 일부를 형성한다는 것을 인정하는 것으로 간주되지 않는다는 것을 이해할 것이다. 참고 문헌의 임의의 논의는 저자가 주장하는 것이 무엇인지를, 그리고 출원인은 본원에서 인용된 문헌 중 임의의 것의 정확성 및 적절성에 관하여 이의를 제기할 수 있는 권리를 보유하고 있다는 것을 언급한다. 달리 명확하게 명시되지 않는 한, 본원에서 인용된 모든 참고 문헌은 그 전체가 참조로 포함된다. 인용된 참고 문헌에서 발견되는 임의의 정의 및/또는 설명 사이에 임의의 차이가 존재할 경우, 이때는 본 개시내용이 조정하여야 한다. 언급된 임의의 참고 문헌이 본 발명과 관련하여 선행 기술인 것으로 인정되는 것은 아니다.
하기 실시예는 단지 예시적인 것으로 의도되며, 본 발명 또는 첨부된 청구범위의 범주 실시양태를 한정하는 것으로 의도되지 않는다.
실시예
실시예 1:
참여자 선별
임상 시험 심사 위원회(Institutional Review Board) 승인하에 AR, OK, TN 및 WA의 유방 건강 및 수술 센터(Breast Health and Surgery Centers)에서 진찰받은 환자로부터 연구 참여자를 모집하였다. 샘플 수집 전, 또는 환자 정보 시트 작성을 완료하기 전에 모든 환자는 동의하였고, 사전 동의서 사본을 제공받았다. 샘플은 임상 진료소 직원 (즉, 간호사 및 전문 기술자) 및/또는 어센던트 Dx(Ascendant Dx) 직원에 의해 수집되었다. 환자 선별에 사용된 포함/배제 기준은 하기와 같았다:
포함 기준:
18-100세 사이인 개체,
일반 검진을 위해 참석한 개체, 또는
이상 검사 또는 시험 평가를 위해 참석한 개체, 또는
촉진성 종괴 평가를 위해 참석한 개체, 또는
종괴 중 일부가 여전히 남아있는 한, 생검 이전 또는 이후에 상기 종괴를 보이는 개체,
최근 유방암 진단을 받았지만, 어떤 종류의 치료도 받지 않은 개체.
배제 기준:
18세 미만 또는 100세 초과인 개체,
동시 눈 감염 또는 외상을 갖는 개체, 또는
현재 급성 결막염을 가지고 있는 개체, 또는
유방암 진단을 받고, 치료를 받은 적인 있는 개체.
대조군 샘플은 일반 스크리닝 유방조영상을 위해 진찰받았지만, 추가 시술을 위한 재통보는 받지 않은 환자로부터 수집하였다. 양성 샘플은 생검 시점에 수집하였고, 일단 병리 결과가 측정되고 나면, 양성 군에 포함시켰다. 암 샘플을 또한수술 전 MRI를 받은 환자로부터, 및 수술 전 감시 림프절 시술을 받은 환자로부터 생검 시점에 수집하고, 병리 결과가 알려진 후에는 암 군에 포함시켰다.
참여자로부터 수집한 데이터로는 하기의 것을 포함하였다: 연령, 성별, 인종, 현재 피임 중인지 또는 호르몬 대체 요법을 받고 있는지 여부, 안과적 감염, 현재 또는 최근 화학요법 치료를 받았는지 여부, 암에 대한 가족력, 이용가능할 경우, 유전자 검사 (BRAC1/2), 암 병기 (I, II, III, IV), 암 유형 (유관 상피내 암종, 침습성 유관 암종, 침습성 소엽성 암종, 소엽성 상피내 암종, 및 상세불명인 것), 호르몬 수용체 상태 (ER+/-, PR+/-, HER2+/-), 종괴 크기, 종양 등급 (I, II, III), 유방 밀도 점수 (카테고리 1, 2, 3, 또는 4로 확인되는 밀도) 및 이전 암 병력.
실시예 2:
쉬르머(Schirmer) 스트립 샘플 수집 방법
쉬르머 스트립 (굴덴 (GuldenOpthalmics: 미국 펜실베이니아 주 엘킨스 파크))을 이용하여 눈물을 수집하기 위해 임상 시험 심사 위원회 승인을 받았다. 수집을 위해, 립을 형성하는 0 mm 선에서 쉬르머 스트립의 둥근 끝단을 접었다. 참여자의 아랫 눈꺼풀에 접힌 부분을 놓고, 참여자에게 눈을 감고, 5분 동안 감은 상태로 그 위치에 상기 접힌 부분이 그대로 유지될 수 있게 해달라고 요청하였다. 5분 경과 후, 스트립을 제거하고, 1.5 mL의 미리 표지된, 멸균 스냅 탑 튜브에 놓고, 이용가능성에 따라 -20℃ 또는 -80℃에 놓았다. 수집 기준은, 5분이 되기 전에 35 mm에 도달하였다면, 스트립을 제거할 수 있다는 것으로 명시되었다. 참가 임상 진료소에서 수집된 샘플은 매주 어센던트 Dx 직원이 회수하여 드라이 아이스 상에서 어센던트 Dx 실험 시설로 보냈다.
실시예 3:
쉬르머 스트립 샘플 프로세싱
먼저 멸균 집게 및 가위를 사용하여 스트립을 다이싱하여 깨끗한 멸균 1.5 mL 스탭 탑 튜브에 넣어 단백질 용리를 수행하였다. 다이싱 스트립에 200 μL의 1X 포스페이트-완충처리된 염수 (PBS)를 첨가하고, 샘플을 3시간 동안 가볍게 진탕시키면서 4℃에서 인큐베이션시켰다. 용리시킨 후, 샘플을 테이블탑 원심분리기에서 단시간 동안 회전시켜 튜브 하부의 스트립 단편을 수집하고, 상청액은 새로운 깨끗한 1.5 mL 스탭 탑 튜브로 옮겨 놓았다. 표준 비신코닌산 (BCA) 검정법을 이용하여 전체 단백질 함량을 측정하고, 추가 사용시까지 샘플을 -80℃에서 보관하였다.
BCA 검정용 키트 (피어스(Pierce))를 이용하여 각 풀의 전체 단백질 함량을 측정하였고, 여기서, 표준 및 비공지물 대 작업 시약의 비는 1:20 (v/v)이고, 37℃에서 인큐베이션 시간은 30 분이었다. 확실하게 신뢰가능한 전체 단백질 함량을 계산할 수 있도록 하기 위해 각 샘플에 대해 일련의 희석액을 제조하였고, 모든 희석액을 3중으로 플레이팅하였다. 희석된 알부민 (2 mg/ml, 1.5 mg/ml, 1m/ml, 0.75 mg/ml, 0.5 mg/ml, 0.25 mg/ml 0.125 mg/ml 0.025 mg/ml 및 0 mg/ml)을 사용하여 표준 곡선을 작성하고, 블랭크 감산을 모든 표준 및 비공지물에 적용시켰다. 표준 곡선의 4-파라미터 피트를 사용하여 각 비공지물에 대한 단백질 농도를 계산하였다. 농도에 희석률을 곱하고, 평균값을 구하여 전체 단백질 함량을 정확하게 계산하였다. 변동 계수 (%CV)가 15% 이하일 경우에 검정법은 유효한 것으로 간주하였다.
실시예 4:
LC MS/MS에 의한 무표지 정량화 방법 및 결과
실험 1: 아칸소 의과 대학(University of Arkansas for Medical Sciences: UAMS) 프로테오믹 코어(Proteomic Core)에 의해 25개의 유방암 샘플, 25개의 양성 샘플, 및 25개의 대조군 샘플에 관하여 용액 중 트립신 분해 후, LC MS/MS를 수행하였다. 10 mM 트리스[2-카르복시에틸]포스핀 (피어스) 중에서 환원시키고, 50 mM 아이오도아세트아미드 (시그마-알드리치(Sigma-Aldrich)) 중에서 알킬화한 후, 100 ng 돼지 트립신 (프로메가(Promega))을 첨가하고, 37℃에서 12-16시간 동안 인큐베이션시킴으로써 100 mM 중탄산암모늄 (시그마-알드리치) 중 75개의 샘플 모두에 대해 용액 중 분해를 수행하였다. 이어서, 펩티드 생성물을 0.1% 포름산 (플루카(Fluka)) 중에서 산성화시켰다. 트립신 분해 펩티드를 나노액쿼티(nanoAcquity) UPLC 시스템 (워터스(Waters))을 사용하여 100 x 0.075 mm 칼럼 상에서 역상 쥬피터 프로테오(Jupiter Proteo) 수지 (페노메넥스(Phenomenex))에 의해 분리하였다. A:B의 비가 97:3 내지 35:65인 완충제로 이루어진 80 min 간의 구배를 이용하여 펩티드를 용리시켰다 [완충제 A = 0.1% 포름산, 0.05% 아세토니트릴; 완충제 B = 0.1% 포름산, 75% 아세토니트릴]. 용리된 펩티드를 전자 분무 (1.8 kV)에 의해 이온화시킨 후, LTQ 오르비트랩 벨로스(LTQ Orbitrap Velos) 질량 분석기 (써모(Thermo)) 상에서 충돌 유도 해리를 이용하여 MS/MS 분석을 수행하였다. 375 내지 1500 m/z 범위에 걸쳐 60,000 해상도로 프로파일 모드로 FTMS 분석기를 사용하여 MS 데이터를 획득하였다. 35.0인 정규화된 충돌 에너지와 함께 정상 질량 범위 및 중심 모드의 이온 포획 분석기를 이용하여 각 MS 스캔으로부터 상위 15개의 피크에 대한 MS/MS 데이터를 획득하였다. 마스코트(Mascot) 검색 엔진 (매트릭스 사이언스(Matrix Science)) 또는 맥스퀀트(MaxQuant) 정량 프로테오믹스 소프트웨어 (맥스 플랜크 인슈티튜트(Max Planck Institute))를 데이터베이스 검색하여 MS/MS 스펙트럼으로부터 단백질을 확인하였다. 스캐폴드(Scaffold) (프로테옴 소프트웨어)(Proteome Software))를 이용하여 마스코트 검색 결과를 컴파일링하였다.
변경된 유방 병리를 나타낼 수 있는 단백질 군을 선별하기 위해 하기 기준을 설정하였다: 1) (암과 관련하여 양의 방향으로든 또는 음의 방향으로든) 단백질 변화 배수가 1.5배 이상이다. 2) 변화 배수는 p 값이 <0.05인 것을 동반하여야 한다. 3) 단백질은 25개의 암 샘플 중 12개에 존재한다. 상기 기준을 사용함에 따라 500개 초과의 목록은 하기 단백질: 알파-1-항트립신 (A1AT), 항류코프로테이나제 (SLP1), 코필린 (COF1), 항트롬빈-III (ANT3), 베타-2-마이크로글로불린 (B2MG), 단백질-글루타민-감마-글루타밀트랜스퍼라제 (B4DIT7), 미규명 단백질 (B8ZZQ6), 칼모듈린-유사 단백질 5 (CALL5), 시스타틴-B (CYTB), 호중구 데펜싱-1 (DEF1), 데스트린 (DEST), 칼리오신-1 (E7ER44), Rab GDP 해리 억제제 베타의 클러스터 (E7EU23), 신장 인자 1-알파 (EF1A1), 에즈린 (EZRI), 헴-결합 단백질 2 (HEB2), 열 쇼크 동족체 71 (HSP7C), 열 쇼크 단백질 베타 1 (HSPB1), Ig 중쇄 V-III (HV303), Ig 중쇄 V-III 영역 BRO의 클러스터 (HV305), 리포칼린-1 (LCN1), 갈렉틴-3 (LEG3), Ig 람다 쇄 V-IV (LV403), Ig 뮤 쇄 c 영역의 이소폼 2 (P01871), 이소폼 2 열 쇼크 단백질의 클러스터 (P07900-2), 14-3-3 단백질 제타 델타의 클러스터 (P63104), 페릴리핀-3 (PLIN3)의 이소폼 3, 프로테아좀 활성인자 복합체 서브유니트 1 (Q06323), UMP-CMP 키나제 (Q5T0D2), 단백질 S100-A4 (S10A4), S100-A8 (S10A8), 단백질 S100-A9 (S10A9), 단백질 S100-A11 (S10AB), 하악선 안드로겐 조절 단백질 (SMR3B), 아연-알파-2-당단백질 (ZA2G), 자이모겐 과립 단백질 16 동족체 B (ZG16B)로 축소되었다.
실험 2: 각 군의 50개의 샘플을 사용하여 용액 중 트립신 분해 후, LC MS/MS를 반복하였다. 실험 1에 대하여 기술된 것과 같은 방법을 실험 2에 대하여 사용하였다. 샘플 크기 증가로 인해 실험 1에서 관찰된 경향 중 일부는 소실됨과 동시에, 실험 1에서 출현한 경향이 실험 2에서 더욱 현저하게 나타나기도 하였다. 상기 데이터로부터 실험 1에 기술된 500개의 단백질로 이루어진 목록은 추가로 103개의 관심 단백질로 정제되었다. 이 목록은 히스티딘 트리아드 뉴클레오티드-결합 단백질 1 (D6RD60), S100A9 (S10A9), S100A8 (S10A8), 갈렉틴-3-결합 단백질 (LG3BP), Ig 알파-1 쇄 C 영역의 클러스터 (IGHA1), Ig 카파 쇄 V-III 영역 HAH의 클러스터 (KV312), VEGF 공조절형 케모카인 1 (VCC1), L-락테이트 데히드로게나제 A 쇄 (LDHA), 알도-케토리덕타제 패밀리 1 구성원 C (AKR1C1), 루트레틴 (B1AKD8), L-락테이트 데히드로게나제 B 쇄 (LDHB), 망막 데히드로게나제 1 (AL1A1), 미규명 단백질 (B4E1Z4), 알파-1-항키모트립신 (AACT), 슈퍼옥시드 디스뮤타제 [Cu-Zn] (SODC), SPARC-유사 단백질 1 (SPRL1), Ig 중쇄 V-III 영역 TIL (HV304), 케라틴 (K1C9), 시스타틴-SN (CYTN), 알파-악티닌-4 (ACTN4), Ig 람다-3 쇄 C 영역 (단편) (IGLC3), 면역글로불린 람다-유사 폴리펩티드 5 (IGLL5), 알콜 데히드로게나제 1C (ADHIG), 말레이트 데히드로게나제, 미토콘드리아 (MDHM), 칼모듈린-유사 단백질 5 (CALL5), 알파-1-항트립신 (A1AT), 알파-1B-당단백질 (A1BG), 류신이 풍부한 알파-2-당단백질 (A2GL), 소형 유비퀴틴-관련 변형인자 3 (A8MU27), 앞 구배 단백질 2 동족체 (AGR2), 프로필린-1 (PROF1), Ig 람다 쇄 V-III 영역 LOI의 클러스터 (LV302), 프로트롬빈 (E9PIT3), 헤모펙신 (HEMO), Ig 감마-2 쇄 C 영역 (IGHG2), 유비퀴틴-40S 리보솜 단백질 S27a (RPS27A), 아파민 (AFAM), 아포지질단백질 A-I (APOA1), 아포지질단백질 A-IV (APOA4), 플라빈 리덕타제 (NADPH)(BLVRB), 프로사포신 (PSAP), 라크리틴 (LACRT), 60S 산성 리보솜 단백질 P1 (RLA1), 인터-알파-트립신 억제제 중쇄 H2 (ITIH2), 뮤신-유사 단백질 1 (MUCL1), S100 A6 (S100A6), Na(+)/H(+) 교환 조절 보조인자 NHE-RF1 (NHRF1), 티오레독신 도메인-함유 단백질 17 (I3L0K2), 림프구-특이 단백질 (LSP1), 합토글로빈의 클러스터 (H3BS21), 미오신 조절 경쇄 12A (J2QRS3), 리보뉴클레아제 억제제 (RINI), 알파-에놀라제 (ENOA), Ig 카파 쇄 V-I 영역 EU의 클러스터 (KV106), 알콜 데히드로게나제 부류 4 뮤/시그마 쇄 (ADH7), 단백질 AMBP (AMBP), 안지오텐시노겐 (ANGT), 항트롬빈-III (ANT3), 아포지질단백질 A-II (APOA2), 칼페스타틴 (B7Z574), 뇌 산성 가용성 단백질 1 (BASP1), 알파-2-HS-당단백질 (C9JV77), 칼레티쿨린 (CALR), 칼페인-1 촉매성 서브유니트 (CAN1), 세포 분열 조절 단백질 42 동족체 (CDC42), 보체 C3 (CO3), 코로닌-1A (COR1A), 프로그램화된 세포 사멸 6-상호작용 단백질 (DCD), 데핀신 1 (DEF1), F-박스 유일 단백질 50 (FBX50), 감마-글루타밀시클로트랜스퍼라제 (GGCT), 글루타티온 리덕타제, 미토콘드리아 (GSHR), 케라틴, II형 세포골격 1 (K2C1), UMP-CMP 키나제 (KCY), 메소텔린 (MSLN), N-아세틸무라모일-L-알라닌 아미다제 (PGRP2), 니코티네이트 포스포리보실트랜스퍼라제 (PNCB), 인터-알파-트립신 억제제 중쇄 H1 (ITIH1), 리보뉴클레아제 T2 (RNASET2), 슈퍼옥시드 디스뮤타제 [Mn], 미토콘드리아 (SODM), 소형 프롤린이 풍부한 단백질 3 (SPRR3), Src 기질 코탁틴 (SRC8), 튜뷸린 베타-4B 쇄의 클러스터 (TBB4B), 트로포미오신 알파-3 쇄 (TPM3), 세로트랜스페린 (TRFE), 글루타티온 S-트랜스퍼라제 P (THIO), 비트로넥틴 (VTNC), 비타민 D 결합 단백질 (Q6LDC6), 인터-알파-트립신 억제제 중쇄 H4 (ITIH4), 메탈로프로테아제 억제제 (TIMP1), 열 쇼크 단백질 90 (HSP90), 카텝신 B (CATB), 셀룰로플라즈민 (CERU), 칼프로텍틴, 14-3-3 시그마 (1433S), 알파-2-hs-당단백질 (FETUA), 알파-2-마크로글로불린 (A2MG), 트랜스티레틴 (TTHY)을 포함한다 (별첨 1). JMP프로11(JMPpro11) 통계학적 소프트웨어 패키지를 사용하여 분석하기 위해 확인된 단백질로 이루어진 완전한 목록을 스캐폴드(Scaffold) 소프트웨어로부터 전송하였다.
실시예 5:
JMP프로11 소프트웨어를 이용한 통계학적 분석
실험 1: 75개의 샘플 모두에 대하여 앞서 확인된 각각의 단백질의 스펙트럼 강도와 함께 마이크로소프트 엑셀(Microsoft Excel)® 스프레드시트 소프트웨어를 사용함으로써 데이터를 조직화하였다. 스프레드시트에는 또한 샘플 상태 (암, 양성, 대조군) 암 유형, 종양 크기 분류 (1=0.1 mm-1 cm, 2=1.1-2.9 cm, 3=3 cm 이상) 및 종양 등급 상태도 포함되어 있었다. 분석을 위해 상기 스프레드시트를 JMP프로11 소프트웨어 패키지로 업로드하였다.
암 샘플과 대조군 샘플 사이에 2항 선형 회귀가 적용되었다. 6개의 단백질은 그의 S자형 곡선 및 p 값에 기초하여 유의적인 것으로 확인되었고, 이는 Ig 람다 쇄 V-IV (LV403), Ig 중쇄 V-III 영역 BRO (HV305), Ig 중쇄 V-III VH26 (HV303), 리포칼린-1 (LCN1), 베타-2-마이크로글로불린 (B2MG), 아연-알파-2-당단백질 (ZA2G)이었다. 6개의 단백질은 모두 암과 관련하여 하향 조절된 것으로 나타났다. 상기 단백질의 하향 조절이 유방암에 특이적인 것인지 여부를 결정하기 위해, 양성 및 대조군 사이의 2항 선형 회귀를 반복하였다. 이러한 비교 결과, 앞서 확인된 6개의 단백질은 양성 샘플에서도 또한 하향 조절된 것으로 나타났고, 4개의 추가 단백질: 항류코프로테이나제 (SLP1), 칼모듈린-유사-단백질 5 (CALL5), 시스타틴 B (CYTB), 및 갈렉틴-3 (LEG3)이 양성 및 대조군 사이에 유의적인 것으로 확인되었다.
모든 군 사이의 분화 정도를 측정하기 위해 3개 군 모두, 및 10개 단백질 모두를 사용하여 명목형 로지스틱 회귀를 수행하였다. 10개 단백질로 이루어진 군에 대한 오분류 정도는 12%였다. 각 카테고리에 대한 수신자 조작기 곡선을 통해 암의 경우, 0.96, 양성인 경우, 0.94, 및 대조군의 경우, 0.98인 AUC 값을 얻었다 (도 1). 각 단백질에 의해 3개의 카테고리의 샘플에 대한 이동 평균 값을 확보하기 위해 일원 ANOVA 분석을 미리 형성하였다 (도 3).
실험 2: 질량 분석법으로부터 확인된 단백질 모두에 대하여 기록된 스펙트럼 강도를 사용하여 일원 ANOVA 분석을 미리 형성하였다. 모든 단백질에 대하여 트립신 분해 펩티드 생성물을 분석하였다. 단백질을 3가지 방식: 1) 대조군 대 암, 2) 암 대 양성, 3) 양성 대 대조군으로 비교하였다. 알파 수준이 0.05인 것을 군 사이의 유의적인 발현 변화에 관한 지표로서 사용하였다. 트립신 분해 단편의 스펙트럼 강도의 변동을 비교하였다. 대조군과 비교하여 유방암 샘플 중에서 발현 수준이 증가된 일련의 단백질을 확인하였다. 대조군과 비교하여 유방암 샘플 중에서 발현이 감소된 단백질 또한 확인하였다. 실험적 타당성을 확인하기 위해, 그의 발현이 시험된 모든 군들 사이에서 일정하게 유지된 단백질이 존재하였다는 것을 확립하였다 (도 4).
500개의 단백질로 이루어진 초기 목록은 103개의 관심 단백질로 축소되었다. 상기 단백질 군에는 유방암과 관련하여 발현이 증가된 단백질 뿐만 아니라, 유방암과 관련하여 발현이 감소된 단백질이 포함되어 있다 (도 4). 질환의 결과로서 존재할 수 있는 전체 단백질 서열, 트립신 분해 펩티드, 및 서열 이상의 진단 능력이 모두 관심의 대상이 된다.
실시예 6:
ELISA 분석
질량 분석법에 의해 대조군 샘플과 비교하여 암 샘플 중에서 발현 수준이 증가된 일련의 단백질을 관찰하였고, ELISA를 사용하여 추가로 확인하기 위해 수개의 후보 물질을 선택하였다. S100A9는 대조군과 비교하여 유방암 환자의 눈물 중에서 발현이 증가된 것의 대표적인 예로서 선택하였다. LG3BP는 대조군 샘플과 비교하여 유방암 샘플 중에서 발현 수준이 감소된 단백질의 대표로서 제시된다. 표준 ELISA 프로토콜을 사용하여 눈물 중의 발현 수준을 평가하였다. R&D 시스템즈(R&D Systems: 미국 미네소타주 미니애폴리스)로부터 구입한 듀오세츠(DuoSets)와 같은 키트를 사용하여 S100A9 및 LG3BP에 대한 데이터를 얻었다. R&D 시스템즈이 제공하는 설명서에 따라 ELISA 방법을 수행하였다. 간략하며, 1XPBS 중에서 권고된 작업 농도 (GAL3BP 1.0 ug/ml; S100A9 0.5 ug/ml)로 희석된, 100 μL/웰의 포획 항체를 고결합 96 웰 플레이트에 첨가하고, 실온에서 밤새도록 (~16hrs) 인큐베이션시켰다. 플레이트를 0.05% 트윈(Tween)을 포함하는 1XPBS로 4회에 걸쳐 세정하고, 깨끗한 흡수지에 대해 블롯팅하여 매회 세정 이후의 임의의 미량의 액체를 제거하였다. 매 검정 단계 후에는 세정 사이클을 수행하였다. 차단 완충제 (1% BSA를 포함하는 1XPBS)를 모든 웰에 첨가하고 (~200 μL/웰), 플레이트를 실온에서 2시간 동안 인큐베이션시켰다. 1% BSA를 포함하는 1XPBS를 사용하여 눈물 샘플을 S100A9에 대해서는 1:10 내지 1:50, 및 갈렉틴 3 결합 단백질에 대해서는 1:100 & 1:500인 희석률로 희석하였다. 앞서 최적화 검정법으로부터 얻은 결과에 기초하여 각 검정법에 대한 표준 곡선 중 선형 영역에 포함되는 것으로 공지된 희석률을 선택하였다. 샘플 및 표준을 100 μL/웰을 사용하여 이중으로 시험하고, 실온에서 2시간 동안 인큐베이션시켰다. 검출 항체를 권고된 작업 농도 (GAL3BP 2 ug/ml 및 S100A9 1 ug/ml)로 희석하고, 100 μL를 각 웰에 첨가하고, 플레이트를 실온에서 2시간 동안 인큐베이션시켰다. 스트렙트아비딘-HRP 용액을 각 웰에 첨가하고 (100 μL/웰), 실온에서 15 분 동안 인큐베이션시켰다. TMB 기질 용액을 첨가하여 시각화하였다. 15분 경과 후, 50 μL의 1M H2SO4를 각 웰에 첨가하고, 450 nm에서 흡광도를 측정하였다. 그래프패드(GraphPad)로부터 이용가능한 프리즘(Prism) 버전 6.0을 이용하여 ELISA 데이터를 분석하였다.
ELISA 데이터의 통계학적 분석: 통계학적 평가를 위해, 프리즘 소프트웨어에 의해 계산된 각 단백질의 농도를 JMP 프로11로 전송하였다. ELISA 검정법을 이용하여 대조군, 암 또는 양성 샘플에 대해 조사하기 위해 다수의 후보 물질을 선택하였다. 대조군과 비교하여 유방암 눈물 샘플 중에서 단백질 발현이 증가된 것 및 감소된 것의 대표적인 예를 제공하기 위해 두 단백질 (S100A9 및 갈렉틴-3-결합 단백질)의 결과를 제시한다 (각각 도 5 및 6). 3개 군 모두를 평가하였을 때, 63개의 유방암 샘플, 79개의 대조군 샘플, 및 92개의 양성 샘플에 대한 S100A9의 ANOVA 결과로 p 값 = 0.0005를 얻었다. S100A9에 대한 군의 평균은 유방암 = 5673.02 pg/ml; 대조군 = 2130.18 pg/ml; 양성 = 6179.10 pg/ml였다. S100A9 발현에 있어서, 대조군 샘플과 비교하였을 때, 암 샘플에서는 2.6배만큼 증가, 및 대조군과 비교하였을 때, 양성 샘플에서는 2.9배만큼 증가가 이루어졌다. 3개 군 모두를 평가하였을 때, 66개의 유방암 샘플, 55개의 대조군 샘플, 및 54개의 양성 샘플에 대한 갈렉틴-3 결합 단백질의 ANOVA 결과로 p 값 < 0.0001을 얻었다. LG3BP에 대한 군의 평균은 유방암 = 24448.1 pg/ml; 대조군 = 70242.2 pg/ml; 양성 = 62329.7 pg/ml였다. LG3BP는 암 샘플과 비교하였을 때, 대조군 샘플에서는 2.8배 증가, 및 암과 비교하였을 때, 양성 샘플에서는 2.5배 증가를 보였다.
상기 2가지 대표 단백질을 사용하여 유방암 샘플 및 대조군 샘플에 대한 명목형 로지스틱 회귀 분석을 수행하였다. S100A9에 대하여 작성된 ROC 곡선의 AUC는 0.78220이고 (도 7), LG3BP 경우의 AUC는 0.76088이었다 (도 8). 두 단백질을 사용하여 분석을 반복하였고, 얻은 AUC는 0.84250이었다 (도 9).
샘플 집단 특징: 가능한 많은 샘플에 대한 임상 데이터, 예컨대, 유방 밀도, 암 유형, 및 종양 크기를 얻었다.
실험 1: 시험된 75개의 샘플 중에서 41개의 샘플에 대한 유방 밀도 점수를 얻었다. 유방 밀도에 의해 샘플 집단을 분석한 결과, 카테고리 1은 14%, 카테고리2는 36.6%, 카테고리 3은 43.9%, 카테고리 4는 4.7%였다 (도 2). 유관내 암종 (IDC) 진단을 받은 환자로부터는 25개의 암 샘플 중 18개가 수집되었다. 2명의 환자가 유관 상피내 암종 (DCIS) 진단을 받았는데, 1명의 환자는 소엽성 상피내 암종 (LCIS) 진단을 받았고, 1명의 환자는 소엽내 암종 (ILC)을 받았다.
분류하기 위해, 종양 < 20 mm인 것은 "소형" 부류로 분류되고, 종양이 21 mm-99 mm인 것은 "중간" 부류로 지정되고, 종양 > 1cm인 것은 "대형" 부류로 지정되는 척도를 디자인하였다. 유방암 환자로부터 수집된 샘플 중 17개가 대형 종양으로 분류되었고, 2개의 샘플이 중간인 것으로 분류되었고, 6개가 소형인 것으로 분류되었다. 상기 암 샘플 중 8개에 대한 수용체 유형의 병리 정보를 얻었다. 1개의 샘플은 ER-/HER2-였고, 1개의 샘플은 ER-/PR-였고, 2개의 샘플은 ER+/HER2-였고, 3개의 샘플은 ER+/HER2+였고, 1개의 샘플은 ER+/PR-였다.
실험 2: 본 연구에서 분석된 샘플 풀은 5.9%의 카테고리 1 유방 조직; 50%의 카테고리 2, 37.8%의 카테고리 3, 및 5.4%의 카테고리 4로 이루어졌다. 유방 조직 유형이 단백질 발현 수준에 영향을 주는지 여부를 측정하기 위해, ELISA에 의해 평가된 수개의 단백질에 대하여 ANOVA 분석을 수행하였다. 연구된 두 단백질에 대한 대표적인 데이터가 제공되어 있다 (도 10 및 도 11). 알파 수준이 0.05인 것을 사용하였을 때, 도 10 및 11에 제시된, ELISA에서 평가된 각 단백질에 대한 4가지 유형의 유방 조직의 평균에 대하여 어떤 통계학상 유의적인 차이도 관찰되지 않았다.
다양한 유방암 유형으로부터 샘플을 수집하여, DCIS 진단을 받은 환자로부터 17개의 샘플, IDC 진단을 받은 환자로부터 44개의 샘플, DCIS & IDC, 둘 모두를 갖는 환자로부터 4개의 샘플, 및 ILC를 갖는 5개의 샘플을 얻었다. 종양 크기는 굉장히 다양하였다. 실험 1에 기술된 분류 체계를 사용하여 종양 크기가 제공된 샘플의 경우, 대형 종양을 갖는 환자로부터 33개의 샘플을 시험하였고, 종양 크기가 중간 정도인 환자로부터 9개의 샘플을 시험하였고, 종양 크기가 소형인 환자로부터 12개의 샘플을 시험하였다. 수용체 유형이 제공된 38개의 샘플 중 1개의 샘플은 ER-였고, 2개의 샘플은 ER-/HER2-였고, 2개의 샘플은 삼중 음성 (ER-/HER2-/PR-)이었고, 1개의 샘플은 ER-/HER2+였고, 11개의 샘플은 ER+, ER+/HER2 16이었고, 5개의 샘플은 ER+/HER2+였다. 연구된 단백질에 대한 종양 크기, 암 유형, 또는 수용체 상태에 기초하였을 때, 현재까지는 구별되는 어떤 경향도 관찰되지는 않았다.
참고 문헌:
<표 1>
<별첨>
SEQUENCE LISTING <110> Ascendant Diagnostics, LLC <120> Methods of Detecting Cancer <130> IPA160484-US <160> 1162 <170> PatentIn version 3.5 <210> 1 <211> 599 <212> PRT <213> Homo sapiens <400> 1 Met Lys Leu Leu Lys Leu Thr Gly Phe Ile Phe Phe Leu Phe Phe Leu 1 5 10 15 Thr Glu Ser Leu Thr Leu Pro Thr Gln Pro Arg Asp Ile Glu Asn Phe 20 25 30 Asn Ser Thr Gln Lys Phe Ile Glu Asp Asn Ile Glu Tyr Ile Thr Ile 35 40 45 Ile Ala Phe Ala Gln Tyr Val Gln Glu Ala Thr Phe Glu Glu Met Glu 50 55 60 Lys Leu Val Lys Asp Met Val Glu Tyr Lys Asp Arg Cys Met Ala Asp 65 70 75 80 Lys Thr Leu Pro Glu Cys Ser Lys Leu Pro Asn Asn Val Leu Gln Glu 85 90 95 Lys Ile Cys Ala Met Glu Gly Leu Pro Gln Lys His Asn Phe Ser His 100 105 110 Cys Cys Ser Lys Val Asp Ala Gln Arg Arg Leu Cys Phe Phe Tyr Asn 115 120 125 Lys Lys Ser Asp Val Gly Phe Leu Pro Pro Phe Pro Thr Leu Asp Pro 130 135 140 Glu Glu Lys Cys Gln Ala Tyr Glu Ser Asn Arg Glu Ser Leu Leu Asn 145 150 155 160 His Phe Leu Tyr Glu Val Ala Arg Arg Asn Pro Phe Val Phe Ala Pro 165 170 175 Thr Leu Leu Thr Val Ala Val His Phe Glu Glu Val Ala Lys Ser Cys 180 185 190 Cys Glu Glu Gln Asn Lys Val Asn Cys Leu Gln Thr Arg Ala Ile Pro 195 200 205 Val Thr Gln Tyr Leu Lys Ala Phe Ser Ser Tyr Gln Lys His Val Cys 210 215 220 Gly Ala Leu Leu Lys Phe Gly Thr Lys Val Val His Phe Ile Tyr Ile 225 230 235 240 Ala Ile Leu Ser Gln Lys Phe Pro Lys Ile Glu Phe Lys Glu Leu Ile 245 250 255 Ser Leu Val Glu Asp Val Ser Ser Asn Tyr Asp Gly Cys Cys Glu Gly 260 265 270 Asp Val Val Gln Cys Ile Arg Asp Thr Ser Lys Val Met Asn His Ile 275 280 285 Cys Ser Lys Gln Asp Ser Ile Ser Ser Lys Ile Lys Glu Cys Cys Glu 290 295 300 Lys Lys Ile Pro Glu Arg Gly Gln Cys Ile Ile Asn Ser Asn Lys Asp 305 310 315 320 Asp Arg Pro Lys Asp Leu Ser Leu Arg Glu Gly Lys Phe Thr Asp Ser 325 330 335 Glu Asn Val Cys Gln Glu Arg Asp Ala Asp Pro Asp Thr Phe Phe Ala 340 345 350 Lys Phe Thr Phe Glu Tyr Ser Arg Arg His Pro Asp Leu Ser Ile Pro 355 360 365 Glu Leu Leu Arg Ile Val Gln Ile Tyr Lys Asp Leu Leu Arg Asn Cys 370 375 380 Cys Asn Thr Glu Asn Pro Pro Gly Cys Tyr Arg Tyr Ala Glu Asp Lys 385 390 395 400 Phe Asn Glu Thr Thr Glu Lys Ser Leu Lys Met Val Gln Gln Glu Cys 405 410 415 Lys His Phe Gln Asn Leu Gly Lys Asp Gly Leu Lys Tyr His Tyr Leu 420 425 430 Ile Arg Leu Thr Lys Ile Ala Pro Gln Leu Ser Thr Glu Glu Leu Val 435 440 445 Ser Leu Gly Glu Lys Met Val Thr Ala Phe Thr Thr Cys Cys Thr Leu 450 455 460 Ser Glu Glu Phe Ala Cys Val Asp Asn Leu Ala Asp Leu Val Phe Gly 465 470 475 480 Glu Leu Cys Gly Val Asn Glu Asn Arg Thr Ile Asn Pro Ala Val Asp 485 490 495 His Cys Cys Lys Thr Asn Phe Ala Phe Arg Arg Pro Cys Phe Glu Ser 500 505 510 Leu Lys Ala Asp Lys Thr Tyr Val Pro Pro Pro Phe Ser Gln Asp Leu 515 520 525 Phe Thr Phe His Ala Asp Met Cys Gln Ser Gln Asn Glu Glu Leu Gln 530 535 540 Arg Lys Thr Asp Arg Phe Leu Val Asn Leu Val Lys Leu Lys His Glu 545 550 555 560 Leu Thr Asp Glu Glu Leu Gln Ser Leu Phe Thr Asn Phe Ala Asn Val 565 570 575 Val Asp Lys Cys Cys Lys Ala Glu Ser Pro Glu Val Cys Phe Asn Glu 580 585 590 Glu Ser Pro Lys Ile Gly Asn 595 <210> 2 <211> 93 <212> PRT <213> Homo sapiens <400> 2 Met Leu Thr Glu Leu Glu Lys Ala Leu Asn Ser Ile Ile Asp Val Tyr 1 5 10 15 His Lys Tyr Ser Leu Ile Lys Gly Asn Phe His Ala Val Tyr Arg Asp 20 25 30 Asp Leu Lys Lys Leu Leu Glu Thr Glu Cys Pro Gln Tyr Ile Arg Lys 35 40 45 Lys Gly Ala Asp Val Trp Phe Lys Glu Leu Asp Ile Asn Thr Asp Gly 50 55 60 Ala Val Asn Phe Gln Glu Phe Leu Ile Leu Val Ile Lys Met Gly Val 65 70 75 80 Ala Ala His Lys Lys Ser His Glu Glu Ser His Lys Glu 85 90 <210> 3 <211> 103 <212> PRT <213> Homo sapiens <400> 3 Met Ala Asp Glu Ile Ala Lys Ala Gln Val Ala Arg Pro Gly Gly Asp 1 5 10 15 Thr Ile Phe Gly Lys Ile Ile Arg Lys Glu Ile Pro Ala Lys Ile Ile 20 25 30 Phe Glu Asp Asp Arg Cys Leu Ala Phe His Asp Ile Ser Pro Gln Ala 35 40 45 Pro Thr His Phe Leu Val Ile Pro Lys Lys His Ile Ser Gln Ile Ser 50 55 60 Val Ala Glu Asp Asp Asp Glu Ser Val Ile Thr Lys Glu Lys Pro Glu 65 70 75 80 Lys Pro Leu Gly Leu Gln Leu Pro Ser Cys Phe Pro Lys Leu Leu His 85 90 95 His Phe Val Ser His Gln Gln 100 <210> 4 <211> 585 <212> PRT <213> Homo sapiens <400> 4 Met Thr Pro Pro Arg Leu Phe Trp Val Trp Leu Leu Val Ala Gly Thr 1 5 10 15 Gln Gly Val Asn Asp Gly Asp Met Arg Leu Ala Asp Gly Gly Ala Thr 20 25 30 Asn Gln Gly Arg Val Glu Ile Phe Tyr Arg Gly Gln Trp Gly Thr Val 35 40 45 Cys Asp Asn Leu Trp Asp Leu Thr Asp Ala Ser Val Val Cys Arg Ala 50 55 60 Leu Gly Phe Glu Asn Ala Thr Gln Ala Leu Gly Arg Ala Ala Phe Gly 65 70 75 80 Gln Gly Ser Gly Pro Ile Met Leu Asp Glu Val Gln Cys Thr Gly Thr 85 90 95 Glu Ala Ser Leu Ala Asp Cys Lys Ser Leu Gly Trp Leu Lys Ser Asn 100 105 110 Cys Arg His Glu Arg Asp Ala Gly Val Val Cys Thr Asn Glu Thr Arg 115 120 125 Ser Thr His Thr Leu Asp Leu Ser Arg Glu Leu Ser Glu Ala Leu Gly 130 135 140 Gln Ile Phe Asp Ser Gln Arg Gly Cys Asp Leu Ser Ile Ser Val Asn 145 150 155 160 Val Gln Gly Glu Asp Ala Leu Gly Phe Cys Gly His Thr Val Ile Leu 165 170 175 Thr Ala Asn Leu Glu Ala Gln Ala Leu Trp Lys Glu Pro Gly Ser Asn 180 185 190 Val Thr Met Ser Val Asp Ala Glu Cys Val Pro Met Val Arg Asp Leu 195 200 205 Leu Arg Tyr Phe Tyr Ser Arg Arg Ile Asp Ile Thr Leu Ser Ser Val 210 215 220 Lys Cys Phe His Lys Leu Ala Ser Ala Tyr Gly Ala Arg Gln Leu Gln 225 230 235 240 Gly Tyr Cys Ala Ser Leu Phe Ala Ile Leu Leu Pro Gln Asp Pro Ser 245 250 255 Phe Gln Met Pro Leu Asp Leu Tyr Ala Tyr Ala Val Ala Thr Gly Asp 260 265 270 Ala Leu Leu Glu Lys Leu Cys Leu Gln Phe Leu Ala Trp Asn Phe Glu 275 280 285 Ala Leu Thr Gln Ala Glu Ala Trp Pro Ser Val Pro Thr Asp Leu Leu 290 295 300 Gln Leu Leu Leu Pro Arg Ser Asp Leu Ala Val Pro Ser Glu Leu Ala 305 310 315 320 Leu Leu Lys Ala Val Asp Thr Trp Ser Trp Gly Glu Arg Ala Ser His 325 330 335 Glu Glu Val Glu Gly Leu Val Glu Lys Ile Arg Phe Pro Met Met Leu 340 345 350 Pro Glu Glu Leu Phe Glu Leu Gln Phe Asn Leu Ser Leu Tyr Trp Ser 355 360 365 His Glu Ala Leu Phe Gln Lys Lys Thr Leu Gln Ala Leu Glu Phe His 370 375 380 Thr Val Pro Phe Gln Leu Leu Ala Arg Tyr Lys Gly Leu Asn Leu Thr 385 390 395 400 Glu Asp Thr Tyr Lys Pro Arg Ile Tyr Thr Ser Pro Thr Trp Ser Ala 405 410 415 Phe Val Thr Asp Ser Ser Trp Ser Ala Arg Lys Ser Gln Leu Val Tyr 420 425 430 Gln Ser Arg Arg Gly Pro Leu Val Lys Tyr Ser Ser Asp Tyr Phe Gln 435 440 445 Ala Pro Ser Asp Tyr Arg Tyr Tyr Pro Tyr Gln Ser Phe Gln Thr Pro 450 455 460 Gln His Pro Ser Phe Leu Phe Gln Asp Lys Arg Val Ser Trp Ser Leu 465 470 475 480 Val Tyr Leu Pro Thr Ile Gln Ser Cys Trp Asn Tyr Gly Phe Ser Cys 485 490 495 Ser Ser Asp Glu Leu Pro Val Leu Gly Leu Thr Lys Ser Gly Gly Ser 500 505 510 Asp Arg Thr Ile Ala Tyr Glu Asn Lys Ala Leu Met Leu Cys Glu Gly 515 520 525 Leu Phe Val Ala Asp Val Thr Asp Phe Glu Gly Trp Lys Ala Ala Ile 530 535 540 Pro Ser Ala Leu Asp Thr Asn Ser Ser Lys Ser Thr Ser Ser Phe Pro 545 550 555 560 Cys Pro Ala Gly His Phe Asn Gly Phe Arg Thr Val Ile Arg Pro Phe 565 570 575 Tyr Leu Thr Asn Ser Ser Gly Val Asp 580 585 <210> 5 <211> 353 <212> PRT <213> Homo sapiens <400> 5 Ala Ser Pro Thr Ser Pro Lys Val Phe Pro Leu Ser Leu Cys Ser Thr 1 5 10 15 Gln Pro Asp Gly Asn Val Val Ile Ala Cys Leu Val Gln Gly Phe Phe 20 25 30 Pro Gln Glu Pro Leu Ser Val Thr Trp Ser Glu Ser Gly Gln Gly Val 35 40 45 Thr Ala Arg Asn Phe Pro Pro Ser Gln Asp Ala Ser Gly Asp Leu Tyr 50 55 60 Thr Thr Ser Ser Gln Leu Thr Leu Pro Ala Thr Gln Cys Leu Ala Gly 65 70 75 80 Lys Ser Val Thr Cys His Val Lys His Tyr Thr Asn Pro Ser Gln Asp 85 90 95 Val Thr Val Pro Cys Pro Val Pro Ser Thr Pro Pro Thr Pro Ser Pro 100 105 110 Ser Thr Pro Pro Thr Pro Ser Pro Ser Cys Cys His Pro Arg Leu Ser 115 120 125 Leu His Arg Pro Ala Leu Glu Asp Leu Leu Leu Gly Ser Glu Ala Asn 130 135 140 Leu Thr Cys Thr Leu Thr Gly Leu Arg Asp Ala Ser Gly Val Thr Phe 145 150 155 160 Thr Trp Thr Pro Ser Ser Gly Lys Ser Ala Val Gln Gly Pro Pro Glu 165 170 175 Arg Asp Leu Cys Gly Cys Tyr Ser Val Ser Ser Val Leu Pro Gly Cys 180 185 190 Ala Glu Pro Trp Asn His Gly Lys Thr Phe Thr Cys Thr Ala Ala Tyr 195 200 205 Pro Glu Ser Lys Thr Pro Leu Thr Ala Thr Leu Ser Lys Ser Gly Asn 210 215 220 Thr Phe Arg Pro Glu Val His Leu Leu Pro Pro Pro Ser Glu Glu Leu 225 230 235 240 Ala Leu Asn Glu Leu Val Thr Leu Thr Cys Leu Ala Arg Gly Phe Ser 245 250 255 Pro Lys Asp Val Leu Val Arg Trp Leu Gln Gly Ser Gln Glu Leu Pro 260 265 270 Arg Glu Lys Tyr Leu Thr Trp Ala Ser Arg Gln Glu Pro Ser Gln Gly 275 280 285 Thr Thr Thr Phe Ala Val Thr Ser Ile Leu Arg Val Ala Ala Glu Asp 290 295 300 Trp Lys Lys Gly Asp Thr Phe Ser Cys Met Val Gly His Glu Ala Leu 305 310 315 320 Pro Leu Ala Phe Thr Gln Lys Thr Ile Asp Arg Leu Ala Gly Lys Pro 325 330 335 Thr His Val Asn Val Ser Val Val Met Ala Glu Val Asp Gly Thr Cys 340 345 350 Tyr <210> 6 <211> 334 <212> PRT <213> Homo sapiens <400> 6 Met Ala Thr Leu Lys Glu Lys Leu Ile Ala Pro Val Ala Glu Glu Glu 1 5 10 15 Ala Thr Val Pro Asn Asn Lys Ile Thr Val Val Gly Val Gly Gln Val 20 25 30 Gly Met Ala Cys Ala Ile Ser Ile Leu Gly Lys Ser Leu Ala Asp Glu 35 40 45 Leu Ala Leu Val Asp Val Leu Glu Asp Lys Leu Lys Gly Glu Met Met 50 55 60 Asp Leu Gln His Gly Ser Leu Phe Leu Gln Thr Pro Lys Ile Val Ala 65 70 75 80 Asp Lys Asp Tyr Ser Val Thr Ala Asn Ser Lys Ile Val Val Val Thr 85 90 95 Ala Gly Val Arg Gln Gln Glu Gly Glu Ser Arg Leu Asn Leu Val Gln 100 105 110 Arg Asn Val Asn Val Phe Lys Phe Ile Ile Pro Gln Ile Val Lys Tyr 115 120 125 Ser Pro Asp Cys Ile Ile Ile Val Val Ser Asn Pro Val Asp Ile Leu 130 135 140 Thr Tyr Val Thr Trp Lys Leu Ser Gly Leu Pro Lys His Arg Val Ile 145 150 155 160 Gly Ser Gly Cys Asn Leu Asp Ser Ala Arg Phe Arg Tyr Leu Met Ala 165 170 175 Glu Lys Leu Gly Ile His Pro Ser Ser Cys His Gly Trp Ile Leu Gly 180 185 190 Glu His Gly Asp Ser Ser Val Ala Val Trp Ser Gly Val Asn Val Ala 195 200 205 Gly Val Ser Leu Gln Glu Leu Asn Pro Glu Met Gly Thr Asp Asn Asp 210 215 220 Ser Glu Asn Trp Lys Glu Val His Lys Met Val Val Glu Ser Ala Tyr 225 230 235 240 Glu Val Ile Lys Leu Lys Gly Tyr Thr Asn Trp Ala Ile Gly Leu Ser 245 250 255 Val Ala Asp Leu Ile Glu Ser Met Leu Lys Asn Leu Ser Arg Ile His 260 265 270 Pro Val Ser Thr Met Val Lys Gly Met Tyr Gly Ile Glu Asn Glu Val 275 280 285 Phe Leu Ser Leu Pro Cys Ile Leu Asn Ala Arg Gly Leu Thr Ser Val 290 295 300 Ile Asn Gln Lys Leu Lys Asp Asp Glu Val Ala Gln Leu Lys Lys Ser 305 310 315 320 Ala Asp Thr Leu Trp Asp Ile Gln Lys Asp Leu Lys Asp Leu 325 330 <210> 7 <211> 332 <212> PRT <213> Homo sapiens <400> 7 Met Ala Thr Leu Lys Asp Gln Leu Ile Tyr Asn Leu Leu Lys Glu Glu 1 5 10 15 Gln Thr Pro Gln Asn Lys Ile Thr Val Val Gly Val Gly Ala Val Gly 20 25 30 Met Ala Cys Ala Ile Ser Ile Leu Met Lys Asp Leu Ala Asp Glu Leu 35 40 45 Ala Leu Val Asp Val Ile Glu Asp Lys Leu Lys Gly Glu Met Met Asp 50 55 60 Leu Gln His Gly Ser Leu Phe Leu Arg Thr Pro Lys Ile Val Ser Gly 65 70 75 80 Lys Asp Tyr Asn Val Thr Ala Asn Ser Lys Leu Val Ile Ile Thr Ala 85 90 95 Gly Ala Arg Gln Gln Glu Gly Glu Ser Arg Leu Asn Leu Val Gln Arg 100 105 110 Asn Val Asn Ile Phe Lys Phe Ile Ile Pro Asn Val Val Lys Tyr Ser 115 120 125 Pro Asn Cys Lys Leu Leu Ile Val Ser Asn Pro Val Asp Ile Leu Thr 130 135 140 Tyr Val Ala Trp Lys Ile Ser Gly Phe Pro Lys Asn Arg Val Ile Gly 145 150 155 160 Ser Gly Cys Asn Leu Asp Ser Ala Arg Phe Arg Tyr Leu Met Gly Glu 165 170 175 Arg Leu Gly Val His Pro Leu Ser Cys His Gly Trp Val Leu Gly Glu 180 185 190 His Gly Asp Ser Ser Val Pro Val Trp Ser Gly Met Asn Val Ala Gly 195 200 205 Val Ser Leu Lys Thr Leu His Pro Asp Leu Gly Thr Asp Lys Asp Lys 210 215 220 Glu Gln Trp Lys Glu Val His Lys Gln Val Val Glu Ser Ala Tyr Glu 225 230 235 240 Val Ile Lys Leu Lys Gly Tyr Thr Ser Trp Ala Ile Gly Leu Ser Val 245 250 255 Ala Asp Leu Ala Glu Ser Ile Met Lys Asn Leu Arg Arg Val His Pro 260 265 270 Val Ser Thr Met Ile Lys Gly Leu Tyr Gly Ile Lys Asp Asp Val Phe 275 280 285 Leu Ser Val Pro Cys Ile Leu Gly Gln Asn Gly Ile Ser Asp Leu Val 290 295 300 Lys Val Thr Leu Thr Ser Glu Glu Glu Ala Arg Leu Lys Lys Ser Ala 305 310 315 320 Asp Thr Leu Trp Gly Ile Gln Lys Glu Leu Gln Phe 325 330 <210> 8 <211> 119 <212> PRT <213> Homo sapiens <400> 8 Met Lys Val Leu Ile Ser Ser Leu Leu Leu Leu Leu Pro Leu Met Leu 1 5 10 15 Met Ser Met Val Ser Ser Ser Leu Asn Pro Gly Val Ala Arg Gly His 20 25 30 Arg Asp Arg Gly Gln Ala Ser Arg Arg Trp Leu Gln Glu Gly Gly Gln 35 40 45 Glu Cys Glu Cys Lys Asp Trp Phe Leu Arg Ala Pro Arg Arg Lys Phe 50 55 60 Met Thr Val Ser Gly Leu Pro Lys Lys Gln Cys Pro Cys Asp His Phe 65 70 75 80 Lys Gly Asn Val Lys Lys Thr Arg His Gln Arg His His Arg Lys Pro 85 90 95 Asn Lys His Ser Arg Ala Cys Gln Gln Phe Leu Lys Gln Cys Gln Leu 100 105 110 Arg Ser Phe Ala Leu Pro Leu 115 <210> 9 <211> 501 <212> PRT <213> Homo sapiens <400> 9 Met Ser Ser Ser Gly Thr Pro Asp Leu Pro Val Leu Leu Thr Asp Leu 1 5 10 15 Lys Ile Gln Tyr Thr Lys Ile Phe Ile Asn Asn Glu Trp His Asp Ser 20 25 30 Val Ser Gly Lys Lys Phe Pro Val Phe Asn Pro Ala Thr Glu Glu Glu 35 40 45 Leu Cys Gln Val Glu Glu Gly Asp Lys Glu Asp Val Asp Lys Ala Val 50 55 60 Lys Ala Ala Arg Gln Ala Phe Gln Ile Gly Ser Pro Trp Arg Thr Met 65 70 75 80 Asp Ala Ser Glu Arg Gly Arg Leu Leu Tyr Lys Leu Ala Asp Leu Ile 85 90 95 Glu Arg Asp Arg Leu Leu Leu Ala Thr Met Glu Ser Met Asn Gly Gly 100 105 110 Lys Leu Tyr Ser Asn Ala Tyr Leu Asn Asp Leu Ala Gly Cys Ile Lys 115 120 125 Thr Leu Arg Tyr Cys Ala Gly Trp Ala Asp Lys Ile Gln Gly Arg Thr 130 135 140 Ile Pro Ile Asp Gly Asn Phe Phe Thr Tyr Thr Arg His Glu Pro Ile 145 150 155 160 Gly Val Cys Gly Gln Ile Ile Pro Trp Asn Phe Pro Leu Val Met Leu 165 170 175 Ile Trp Lys Ile Gly Pro Ala Leu Ser Cys Gly Asn Thr Val Val Val 180 185 190 Lys Pro Ala Glu Gln Thr Pro Leu Thr Ala Leu His Val Ala Ser Leu 195 200 205 Ile Lys Glu Ala Gly Phe Pro Pro Gly Val Val Asn Ile Val Pro Gly 210 215 220 Tyr Gly Pro Thr Ala Gly Ala Ala Ile Ser Ser His Met Asp Ile Asp 225 230 235 240 Lys Val Ala Phe Thr Gly Ser Thr Glu Val Gly Lys Leu Ile Lys Glu 245 250 255 Ala Ala Gly Lys Ser Asn Leu Lys Arg Val Thr Leu Glu Leu Gly Gly 260 265 270 Lys Ser Pro Cys Ile Val Leu Ala Asp Ala Asp Leu Asp Asn Ala Val 275 280 285 Glu Phe Ala His His Gly Val Phe Tyr His Gln Gly Gln Cys Cys Ile 290 295 300 Ala Ala Ser Arg Ile Phe Val Glu Glu Ser Ile Tyr Asp Glu Phe Val 305 310 315 320 Arg Arg Ser Val Glu Arg Ala Lys Lys Tyr Ile Leu Gly Asn Pro Leu 325 330 335 Thr Pro Gly Val Thr Gln Gly Pro Gln Ile Asp Lys Glu Gln Tyr Asp 340 345 350 Lys Ile Leu Asp Leu Ile Glu Ser Gly Lys Lys Glu Gly Ala Lys Leu 355 360 365 Glu Cys Gly Gly Gly Pro Trp Gly Asn Lys Gly Tyr Phe Val Gln Pro 370 375 380 Thr Val Phe Ser Asn Val Thr Asp Glu Met Arg Ile Ala Lys Glu Glu 385 390 395 400 Ile Phe Gly Pro Val Gln Gln Ile Met Lys Phe Lys Ser Leu Asp Asp 405 410 415 Val Ile Lys Arg Ala Asn Asn Thr Phe Tyr Gly Leu Ser Ala Gly Val 420 425 430 Phe Thr Lys Asp Ile Asp Lys Ala Ile Thr Ile Ser Ser Ala Leu Gln 435 440 445 Ala Gly Thr Val Trp Val Asn Cys Tyr Gly Val Val Ser Ala Gln Cys 450 455 460 Pro Phe Gly Gly Phe Lys Met Ser Gly Asn Gly Arg Glu Leu Gly Glu 465 470 475 480 Tyr Gly Phe His Glu Tyr Thr Glu Val Lys Thr Val Thr Val Lys Ile 485 490 495 Ser Gln Lys Asn Ser 500 <210> 10 <211> 1266 <212> PRT <213> Homo sapiens <400> 10 Met Gly Pro Leu Met Val Leu Phe Cys Leu Leu Phe Leu Tyr Pro Gly 1 5 10 15 Leu Ala Asp Ser Ala Pro Ser Cys Pro Gln Asn Val Asn Ile Ser Gly 20 25 30 Gly Thr Phe Thr Leu Ser His Gly Trp Ala Pro Gly Ser Leu Leu Thr 35 40 45 Tyr Ser Cys Pro Gln Gly Leu Tyr Pro Ser Pro Ala Ser Arg Leu Cys 50 55 60 Lys Ser Ser Gly Gln Trp Gln Thr Pro Gly Ala Thr Arg Ser Leu Ser 65 70 75 80 Lys Ala Val Cys Lys Pro Gly His Cys Pro Asn Pro Gly Ile Ser Leu 85 90 95 Gly Ala Val Arg Thr Gly Phe Arg Phe Gly His Gly Asp Lys Val Arg 100 105 110 Tyr Arg Cys Ser Ser Asn Leu Val Leu Thr Gly Ser Ser Glu Arg Glu 115 120 125 Cys Gln Gly Asn Gly Val Trp Ser Gly Thr Glu Pro Ile Cys Arg Gln 130 135 140 Pro Tyr Ser Tyr Asp Phe Pro Glu Asp Val Ala Pro Ala Leu Gly Thr 145 150 155 160 Ser Phe Ser His Met Leu Gly Ala Thr Asn Pro Thr Gln Lys Thr Lys 165 170 175 Asp His Glu Asn Gly Thr Gly Thr Asn Thr Tyr Ala Ala Leu Asn Ser 180 185 190 Val Tyr Leu Met Met Asn Asn Gln Met Arg Leu Leu Gly Met Glu Thr 195 200 205 Met Ala Trp Gln Glu Ile Arg His Ala Ile Ile Leu Leu Thr Asp Gly 210 215 220 Lys Ser Asn Met Gly Gly Ser Pro Lys Thr Ala Val Asp His Ile Arg 225 230 235 240 Glu Ile Leu Asn Ile Asn Gln Lys Arg Asn Asp Tyr Leu Asp Ile Tyr 245 250 255 Ala Ile Gly Val Gly Lys Leu Asp Val Asp Trp Arg Glu Leu Asn Glu 260 265 270 Leu Gly Ser Lys Lys Asp Gly Glu Arg His Ala Phe Ile Leu Gln Asp 275 280 285 Thr Lys Ala Leu His Gln Val Phe Glu His Met Leu Asp Val Ser Lys 290 295 300 Leu Thr Asp Thr Ile Cys Gly Val Gly Asn Met Ser Ala Asn Ala Ser 305 310 315 320 Asp Gln Glu Arg Thr Pro Trp His Val Thr Ile Lys Pro Lys Ser Gln 325 330 335 Glu Thr Cys Arg Gly Ala Leu Ile Ser Asp Gln Trp Val Leu Thr Ala 340 345 350 Ala His Cys Phe Arg Asp Gly Asn Asp His Ser Leu Trp Arg Val Asn 355 360 365 Val Gly Asp Pro Lys Ser Gln Trp Gly Lys Glu Phe Leu Ile Glu Lys 370 375 380 Ala Val Ile Ser Pro Gly Phe Asp Val Phe Ala Lys Lys Asn Gln Gly 385 390 395 400 Ile Leu Glu Phe Tyr Gly Asp Asp Ile Ala Leu Leu Lys Leu Ala Gln 405 410 415 Lys Val Lys Met Ser Thr His Ala Arg Pro Ile Cys Leu Pro Cys Thr 420 425 430 Met Glu Ala Asn Leu Ala Leu Arg Arg Pro Gln Gly Ser Thr Cys Arg 435 440 445 Asp His Glu Asn Glu Leu Leu Asn Lys Gln Ser Val Pro Ala His Phe 450 455 460 Val Ala Leu Asn Gly Ser Lys Leu Asn Ile Asn Leu Lys Met Gly Val 465 470 475 480 Glu Trp Thr Ser Cys Ala Glu Val Val Ser Gln Glu Lys Thr Met Phe 485 490 495 Pro Asn Leu Thr Asp Val Arg Glu Val Val Thr Asp Gln Phe Leu Cys 500 505 510 Ser Gly Thr Gln Glu Asp Glu Ser Pro Cys Lys Gly Val Thr Thr Thr 515 520 525 Pro Trp Ser Leu Ala Arg Pro Gln Gly Ser Cys Ser Leu Glu Gly Val 530 535 540 Glu Ile Lys Gly Gly Ser Phe Arg Leu Leu Gln Glu Gly Gln Ala Leu 545 550 555 560 Glu Tyr Val Cys Pro Ser Gly Phe Tyr Pro Tyr Pro Val Gln Thr Arg 565 570 575 Thr Cys Arg Ser Thr Gly Ser Trp Ser Thr Leu Lys Thr Gln Asp Gln 580 585 590 Lys Thr Val Arg Lys Ala Glu Cys Arg Ala Ile His Cys Pro Arg Pro 595 600 605 His Asp Phe Glu Asn Gly Glu Tyr Trp Pro Arg Ser Pro Tyr Tyr Asn 610 615 620 Val Ser Asp Glu Ile Ser Phe His Cys Tyr Asp Gly Tyr Thr Leu Arg 625 630 635 640 Gly Ser Ala Asn Arg Thr Cys Gln Val Asn Gly Arg Trp Ser Gly Gln 645 650 655 Thr Ala Ile Cys Asp Asn Gly Ala Gly Tyr Cys Ser Asn Pro Gly Ile 660 665 670 Pro Ile Gly Thr Arg Lys Val Gly Ser Gln Tyr Arg Leu Glu Asp Ser 675 680 685 Val Thr Tyr His Cys Ser Arg Gly Leu Thr Leu Arg Gly Ser Gln Arg 690 695 700 Arg Thr Cys Gln Glu Gly Gly Ser Trp Ser Gly Thr Glu Pro Ser Cys 705 710 715 720 Gln Asp Ser Phe Met Tyr Asp Thr Pro Gln Glu Val Ala Glu Ala Phe 725 730 735 Leu Ser Ser Leu Thr Glu Thr Ile Glu Gly Val Asp Ala Glu Asp Gly 740 745 750 His Gly Pro Gly Glu Gln Gln Lys Arg Lys Ile Val Leu Asp Pro Ser 755 760 765 Gly Ser Met Asn Ile Tyr Leu Val Leu Asp Gly Ser Asp Ser Ile Gly 770 775 780 Ala Ser Asn Phe Thr Gly Ala Lys Lys Cys Leu Val Asn Leu Ile Glu 785 790 795 800 Lys Val Ala Ser Tyr Gly Val Lys Pro Arg Tyr Gly Leu Val Thr Tyr 805 810 815 Ala Thr Tyr Pro Lys Ile Trp Val Lys Val Ser Glu Ala Asp Ser Ser 820 825 830 Asn Ala Asp Trp Val Thr Lys Gln Leu Asn Glu Ile Asn Tyr Glu Asp 835 840 845 His Lys Leu Lys Ser Gly Thr Asn Thr Lys Lys Ala Leu Gln Ala Val 850 855 860 Tyr Ser Met Met Ser Trp Pro Asp Asp Val Pro Pro Glu Gly Trp Asn 865 870 875 880 Arg Thr Arg His Val Ile Ile Leu Met Thr Asp Gly Leu His Asn Met 885 890 895 Gly Gly Asp Pro Ile Thr Val Ile Asp Glu Ile Arg Asp Leu Leu Tyr 900 905 910 Ile Gly Lys Asp Arg Lys Asn Pro Arg Glu Asp Tyr Leu Asp Val Tyr 915 920 925 Val Phe Gly Val Gly Pro Leu Val Asn Gln Val Asn Ile Asn Ala Leu 930 935 940 Ala Ser Lys Lys Asp Asn Glu Gln His Val Phe Lys Val Lys Asp Met 945 950 955 960 Glu Asn Leu Glu Asp Val Phe Tyr Gln Met Ile Asp Glu Ser Gln Ser 965 970 975 Leu Ser Leu Cys Gly Met Val Trp Glu His Arg Lys Gly Thr Asp Tyr 980 985 990 His Lys Gln Pro Trp Gln Ala Lys Ile Ser Val Ile Arg Pro Ser Lys 995 1000 1005 Gly His Glu Ser Cys Met Gly Ala Val Val Ser Glu Tyr Phe Val 1010 1015 1020 Leu Thr Ala Ala His Cys Phe Thr Val Asp Asp Lys Glu His Ser 1025 1030 1035 Ile Lys Val Ser Val Gly Gly Glu Lys Arg Asp Leu Glu Ile Glu 1040 1045 1050 Val Val Leu Phe His Pro Asn Tyr Asn Ile Asn Gly Lys Lys Glu 1055 1060 1065 Ala Gly Ile Pro Glu Phe Tyr Asp Tyr Asp Val Ala Leu Ile Lys 1070 1075 1080 Leu Lys Asn Lys Leu Lys Tyr Gly Gln Thr Ile Arg Pro Ile Cys 1085 1090 1095 Leu Pro Cys Thr Glu Gly Thr Thr Arg Ala Leu Arg Leu Pro Pro 1100 1105 1110 Thr Thr Thr Cys Gln Gln Gln Lys Glu Glu Leu Leu Pro Ala Gln 1115 1120 1125 Asp Ile Lys Ala Leu Phe Val Ser Glu Glu Glu Lys Lys Leu Thr 1130 1135 1140 Arg Lys Glu Val Tyr Ile Lys Asn Gly Asp Lys Lys Gly Ser Cys 1145 1150 1155 Glu Arg Asp Ala Gln Tyr Ala Pro Gly Tyr Asp Lys Val Lys Asp 1160 1165 1170 Ile Ser Glu Val Val Thr Pro Arg Phe Leu Cys Thr Gly Gly Val 1175 1180 1185 Ser Pro Tyr Ala Asp Pro Asn Thr Cys Arg Gly Asp Ser Gly Gly 1190 1195 1200 Pro Leu Ile Val His Lys Arg Ser Arg Phe Ile Gln Val Gly Val 1205 1210 1215 Ile Ser Trp Gly Val Val Asp Val Cys Lys Asn Gln Lys Arg Gln 1220 1225 1230 Lys Gln Val Pro Ala His Ala Arg Asp Phe His Ile Asn Leu Phe 1235 1240 1245 Gln Val Leu Pro Trp Leu Lys Glu Lys Leu Gln Asp Glu Asp Leu 1250 1255 1260 Gly Phe Leu 1265 <210> 11 <211> 423 <212> PRT <213> Homo sapiens <400> 11 Met Glu Arg Met Leu Pro Leu Leu Ala Leu Gly Leu Leu Ala Ala Gly 1 5 10 15 Phe Cys Pro Ala Val Leu Cys His Pro Asn Ser Pro Leu Asp Glu Glu 20 25 30 Asn Leu Thr Gln Glu Asn Gln Asp Arg Gly Thr His Val Asp Leu Gly 35 40 45 Leu Ala Ser Ala Asn Val Asp Phe Ala Phe Ser Leu Tyr Lys Gln Leu 50 55 60 Val Leu Lys Ala Pro Asp Lys Asn Val Ile Phe Ser Pro Leu Ser Ile 65 70 75 80 Ser Thr Ala Leu Ala Phe Leu Ser Leu Gly Ala His Asn Thr Thr Leu 85 90 95 Thr Glu Ile Leu Lys Gly Leu Lys Phe Asn Leu Thr Glu Thr Ser Glu 100 105 110 Ala Glu Ile His Gln Ser Phe Gln His Leu Leu Arg Thr Leu Asn Gln 115 120 125 Ser Ser Asp Glu Leu Gln Leu Ser Met Gly Asn Ala Met Phe Val Lys 130 135 140 Glu Gln Leu Ser Leu Leu Asp Arg Phe Thr Glu Asp Ala Lys Arg Leu 145 150 155 160 Tyr Gly Ser Glu Ala Phe Ala Thr Asp Phe Gln Asp Ser Ala Ala Ala 165 170 175 Lys Lys Leu Ile Asn Asp Tyr Val Lys Asn Gly Thr Arg Gly Lys Ile 180 185 190 Thr Asp Leu Ile Lys Asp Leu Asp Ser Gln Thr Met Met Val Leu Val 195 200 205 Asn Tyr Ile Phe Phe Lys Ala Lys Trp Glu Met Pro Phe Asp Pro Gln 210 215 220 Asp Thr His Gln Ser Arg Phe Tyr Leu Ser Lys Lys Lys Trp Val Met 225 230 235 240 Val Pro Met Met Ser Leu His His Leu Thr Ile Pro Tyr Phe Arg Asp 245 250 255 Glu Glu Leu Ser Cys Thr Val Val Glu Leu Lys Tyr Thr Gly Asn Ala 260 265 270 Ser Ala Leu Phe Ile Leu Pro Asp Gln Asp Lys Met Glu Glu Val Glu 275 280 285 Ala Met Leu Leu Pro Glu Thr Leu Lys Arg Trp Arg Asp Ser Leu Glu 290 295 300 Phe Arg Glu Ile Gly Glu Leu Tyr Leu Pro Lys Phe Ser Ile Ser Arg 305 310 315 320 Asp Tyr Asn Leu Asn Asp Ile Leu Leu Gln Leu Gly Ile Glu Glu Ala 325 330 335 Phe Thr Ser Lys Ala Asp Leu Ser Gly Ile Thr Gly Ala Arg Asn Leu 340 345 350 Ala Val Ser Gln Val Val His Lys Ala Val Leu Asp Val Phe Glu Glu 355 360 365 Gly Thr Glu Ala Ser Ala Ala Thr Ala Val Lys Ile Thr Leu Leu Ser 370 375 380 Ala Leu Val Glu Thr Arg Thr Ile Val Arg Phe Asn Arg Pro Phe Leu 385 390 395 400 Met Ile Ile Val Pro Thr Asp Thr Gln Asn Ile Phe Phe Met Ser Lys 405 410 415 Val Thr Asn Pro Lys Gln Ala 420 <210> 12 <211> 664 <212> PRT <213> Homo sapiens <400> 12 Met Lys Thr Gly Leu Phe Phe Leu Cys Leu Leu Gly Thr Ala Ala Ala 1 5 10 15 Ile Pro Thr Asn Ala Arg Leu Leu Ser Asp His Ser Lys Pro Thr Ala 20 25 30 Glu Thr Val Ala Pro Asp Asn Thr Ala Ile Pro Ser Leu Arg Ala Glu 35 40 45 Ala Glu Glu Asn Glu Lys Glu Thr Ala Val Ser Thr Glu Asp Asp Ser 50 55 60 His His Lys Ala Glu Lys Ser Ser Val Leu Lys Ser Lys Glu Glu Ser 65 70 75 80 His Glu Gln Ser Ala Glu Gln Gly Lys Ser Ser Ser Gln Glu Leu Gly 85 90 95 Leu Lys Asp Gln Glu Asp Ser Asp Gly His Leu Ser Val Asn Leu Glu 100 105 110 Tyr Ala Pro Thr Glu Gly Thr Leu Asp Ile Lys Glu Asp Met Ser Glu 115 120 125 Pro Gln Glu Lys Lys Leu Ser Glu Asn Thr Asp Phe Leu Ala Pro Gly 130 135 140 Val Ser Ser Phe Thr Asp Ser Asn Gln Gln Glu Ser Ile Thr Lys Arg 145 150 155 160 Glu Glu Asn Gln Glu Gln Pro Arg Asn Tyr Ser His His Gln Leu Asn 165 170 175 Arg Ser Ser Lys His Ser Gln Gly Leu Arg Asp Gln Gly Asn Gln Glu 180 185 190 Gln Asp Pro Asn Ile Ser Asn Gly Glu Glu Glu Glu Glu Lys Glu Pro 195 200 205 Gly Glu Val Gly Thr His Asn Asp Asn Gln Glu Arg Lys Thr Glu Leu 210 215 220 Pro Arg Glu His Ala Asn Ser Lys Gln Glu Glu Asp Asn Thr Gln Ser 225 230 235 240 Asp Asp Ile Leu Glu Glu Ser Asp Gln Pro Thr Gln Val Ser Lys Met 245 250 255 Gln Glu Asp Glu Phe Asp Gln Gly Asn Gln Glu Gln Glu Asp Asn Ser 260 265 270 Asn Ala Glu Met Glu Glu Glu Asn Ala Ser Asn Val Asn Lys His Ile 275 280 285 Gln Glu Thr Glu Trp Gln Ser Gln Glu Gly Lys Thr Gly Leu Glu Ala 290 295 300 Ile Ser Asn His Lys Glu Thr Glu Glu Lys Thr Val Ser Glu Ala Leu 305 310 315 320 Leu Met Glu Pro Thr Asp Asp Gly Asn Thr Thr Pro Arg Asn His Gly 325 330 335 Val Asp Asp Asp Gly Asp Asp Asp Gly Asp Asp Gly Gly Thr Asp Gly 340 345 350 Pro Arg His Ser Ala Ser Asp Asp Tyr Phe Ile Pro Ser Gln Ala Phe 355 360 365 Leu Glu Ala Glu Arg Ala Gln Ser Ile Ala Tyr His Leu Lys Ile Glu 370 375 380 Glu Gln Arg Glu Lys Val His Glu Asn Glu Asn Ile Gly Thr Thr Glu 385 390 395 400 Pro Gly Glu His Gln Glu Ala Lys Lys Ala Glu Asn Ser Ser Asn Glu 405 410 415 Glu Glu Thr Ser Ser Glu Gly Asn Met Arg Val His Ala Val Asp Ser 420 425 430 Cys Met Ser Phe Gln Cys Lys Arg Gly His Ile Cys Lys Ala Asp Gln 435 440 445 Gln Gly Lys Pro His Cys Val Cys Gln Asp Pro Val Thr Cys Pro Pro 450 455 460 Thr Lys Pro Leu Asp Gln Val Cys Gly Thr Asp Asn Gln Thr Tyr Ala 465 470 475 480 Ser Ser Cys His Leu Phe Ala Thr Lys Cys Arg Leu Glu Gly Thr Lys 485 490 495 Lys Gly His Gln Leu Gln Leu Asp Tyr Phe Gly Ala Cys Lys Ser Ile 500 505 510 Pro Thr Cys Thr Asp Phe Glu Val Ile Gln Phe Pro Leu Arg Met Arg 515 520 525 Asp Trp Leu Lys Asn Ile Leu Met Gln Leu Tyr Glu Ala Asn Ser Glu 530 535 540 His Ala Gly Tyr Leu Asn Glu Lys Gln Arg Asn Lys Val Lys Lys Ile 545 550 555 560 Tyr Leu Asp Glu Lys Arg Leu Leu Ala Gly Asp His Pro Ile Asp Leu 565 570 575 Leu Leu Arg Asp Phe Lys Lys Asn Tyr His Met Tyr Val Tyr Pro Val 580 585 590 His Trp Gln Phe Ser Glu Leu Asp Gln His Pro Met Asp Arg Val Leu 595 600 605 Thr His Ser Glu Leu Ala Pro Leu Arg Ala Ser Leu Val Pro Met Glu 610 615 620 His Cys Ile Thr Arg Phe Phe Glu Glu Cys Asp Pro Asn Lys Asp Lys 625 630 635 640 His Ile Thr Leu Lys Glu Trp Gly His Cys Phe Gly Ile Lys Glu Glu 645 650 655 Asp Ile Asp Glu Asn Leu Leu Phe 660 <210> 13 <211> 115 <212> PRT <213> Homo sapiens <400> 13 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 25 30 Val Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glx Trp Val 35 40 45 Gly Ala Ile Glx Gly Leu Ser Val Ser Glx Ser Tyr Ala Asx Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Met Asn 65 70 75 80 Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Lys Gly Lys 85 90 95 Val Ser Ala Tyr Tyr Phe Asx Tyr Trp Gly Glx Gly Thr Leu Val Thr 100 105 110 Val Ser Ser 115 <210> 14 <211> 623 <212> PRT <213> Homo sapiens <400> 14 Met Ser Cys Arg Gln Phe Ser Ser Ser Tyr Leu Ser Arg Ser Gly Gly 1 5 10 15 Gly Gly Gly Gly Gly Leu Gly Ser Gly Gly Ser Ile Arg Ser Ser Tyr 20 25 30 Ser Arg Phe Ser Ser Ser Gly Gly Gly Gly Gly Gly Gly Arg Phe Ser 35 40 45 Ser Ser Ser Gly Tyr Gly Gly Gly Ser Ser Arg Val Cys Gly Arg Gly 50 55 60 Gly Gly Gly Ser Phe Gly Tyr Ser Tyr Gly Gly Gly Ser Gly Gly Gly 65 70 75 80 Phe Ser Ala Ser Ser Leu Gly Gly Gly Phe Gly Gly Gly Ser Arg Gly 85 90 95 Phe Gly Gly Ala Ser Gly Gly Gly Tyr Ser Ser Ser Gly Gly Phe Gly 100 105 110 Gly Gly Phe Gly Gly Gly Ser Gly Gly Gly Phe Gly Gly Gly Tyr Gly 115 120 125 Ser Gly Phe Gly Gly Phe Gly Gly Phe Gly Gly Gly Ala Gly Gly Gly 130 135 140 Asp Gly Gly Ile Leu Thr Ala Asn Glu Lys Ser Thr Met Gln Glu Leu 145 150 155 160 Asn Ser Arg Leu Ala Ser Tyr Leu Asp Lys Val Gln Ala Leu Glu Glu 165 170 175 Ala Asn Asn Asp Leu Glu Asn Lys Ile Gln Asp Trp Tyr Asp Lys Lys 180 185 190 Gly Pro Ala Ala Ile Gln Lys Asn Tyr Ser Pro Tyr Tyr Asn Thr Ile 195 200 205 Asp Asp Leu Lys Asp Gln Ile Val Asp Leu Thr Val Gly Asn Asn Lys 210 215 220 Thr Leu Leu Asp Ile Asp Asn Thr Arg Met Thr Leu Asp Asp Phe Arg 225 230 235 240 Ile Lys Phe Glu Met Glu Gln Asn Leu Arg Gln Gly Val Asp Ala Asp 245 250 255 Ile Asn Gly Leu Arg Gln Val Leu Asp Asn Leu Thr Met Glu Lys Ser 260 265 270 Asp Leu Glu Met Gln Tyr Glu Thr Leu Gln Glu Glu Leu Met Ala Leu 275 280 285 Lys Lys Asn His Lys Glu Glu Met Ser Gln Leu Thr Gly Gln Asn Ser 290 295 300 Gly Asp Val Asn Val Glu Ile Asn Val Ala Pro Gly Lys Asp Leu Thr 305 310 315 320 Lys Thr Leu Asn Asp Met Arg Gln Glu Tyr Glu Gln Leu Ile Ala Lys 325 330 335 Asn Arg Lys Asp Ile Glu Asn Gln Tyr Glu Thr Gln Ile Thr Gln Ile 340 345 350 Glu His Glu Val Ser Ser Ser Gly Gln Glu Val Gln Ser Ser Ala Lys 355 360 365 Glu Val Thr Gln Leu Arg His Gly Val Gln Glu Leu Glu Ile Glu Leu 370 375 380 Gln Ser Gln Leu Ser Lys Lys Ala Ala Leu Glu Lys Ser Leu Glu Asp 385 390 395 400 Thr Lys Asn Arg Tyr Cys Gly Gln Leu Gln Met Ile Gln Glu Gln Ile 405 410 415 Ser Asn Leu Glu Ala Gln Ile Thr Asp Val Arg Gln Glu Ile Glu Cys 420 425 430 Gln Asn Gln Glu Tyr Ser Leu Leu Leu Ser Ile Lys Met Arg Leu Glu 435 440 445 Lys Glu Ile Glu Thr Tyr His Asn Leu Leu Glu Gly Gly Gln Glu Asp 450 455 460 Phe Glu Ser Ser Gly Ala Gly Lys Ile Gly Leu Gly Gly Arg Gly Gly 465 470 475 480 Ser Gly Gly Ser Tyr Gly Arg Gly Ser Arg Gly Gly Ser Gly Gly Ser 485 490 495 Tyr Gly Gly Gly Gly Ser Gly Gly Gly Tyr Gly Gly Gly Ser Gly Ser 500 505 510 Arg Gly Gly Ser Gly Gly Ser Tyr Gly Gly Gly Ser Gly Ser Gly Gly 515 520 525 Gly Ser Gly Gly Gly Tyr Gly Gly Gly Ser Gly Gly Gly His Ser Gly 530 535 540 Gly Ser Gly Gly Gly His Ser Gly Gly Ser Gly Gly Asn Tyr Gly Gly 545 550 555 560 Gly Ser Gly Ser Gly Gly Gly Ser Gly Gly Gly Tyr Gly Gly Gly Ser 565 570 575 Gly Ser Arg Gly Gly Ser Gly Gly Ser His Gly Gly Gly Ser Gly Phe 580 585 590 Gly Gly Glu Ser Gly Gly Ser Tyr Gly Gly Gly Glu Glu Ala Ser Gly 595 600 605 Ser Gly Gly Gly Tyr Gly Gly Gly Ser Gly Lys Ser Ser His Ser 610 615 620 <210> 15 <211> 141 <212> PRT <213> Homo sapiens <400> 15 Met Ala Gln Tyr Leu Ser Thr Leu Leu Leu Leu Leu Ala Thr Leu Ala 1 5 10 15 Val Ala Leu Ala Trp Ser Pro Lys Glu Glu Asp Arg Ile Ile Pro Gly 20 25 30 Gly Ile Tyr Asn Ala Asp Leu Asn Asp Glu Trp Val Gln Arg Ala Leu 35 40 45 His Phe Ala Ile Ser Glu Tyr Asn Lys Ala Thr Lys Asp Asp Tyr Tyr 50 55 60 Arg Arg Pro Leu Arg Val Leu Arg Ala Arg Gln Gln Thr Val Gly Gly 65 70 75 80 Val Asn Tyr Phe Phe Asp Val Glu Val Gly Arg Thr Ile Cys Thr Lys 85 90 95 Ser Gln Pro Asn Leu Asp Thr Cys Ala Phe His Glu Gln Pro Glu Leu 100 105 110 Gln Lys Lys Gln Leu Cys Ser Phe Glu Ile Tyr Glu Val Pro Trp Glu 115 120 125 Asn Arg Arg Ser Leu Val Lys Ser Arg Cys Gln Glu Ser 130 135 140 <210> 16 <211> 911 <212> PRT <213> Homo sapiens <400> 16 Met Val Asp Tyr His Ala Ala Asn Gln Ser Tyr Gln Tyr Gly Pro Ser 1 5 10 15 Ser Ala Gly Asn Gly Ala Gly Gly Gly Gly Ser Met Gly Asp Tyr Met 20 25 30 Ala Gln Glu Asp Asp Trp Asp Arg Asp Leu Leu Leu Asp Pro Ala Trp 35 40 45 Glu Lys Gln Gln Arg Lys Thr Phe Thr Ala Trp Cys Asn Ser His Leu 50 55 60 Arg Lys Ala Gly Thr Gln Ile Glu Asn Ile Asp Glu Asp Phe Arg Asp 65 70 75 80 Gly Leu Lys Leu Met Leu Leu Leu Glu Val Ile Ser Gly Glu Arg Leu 85 90 95 Pro Lys Pro Glu Arg Gly Lys Met Arg Val His Lys Ile Asn Asn Val 100 105 110 Asn Lys Ala Leu Asp Phe Ile Ala Ser Lys Gly Val Lys Leu Val Ser 115 120 125 Ile Gly Ala Glu Glu Ile Val Asp Gly Asn Ala Lys Met Thr Leu Gly 130 135 140 Met Ile Trp Thr Ile Ile Leu Arg Phe Ala Ile Gln Asp Ile Ser Val 145 150 155 160 Glu Glu Thr Ser Ala Lys Glu Gly Leu Leu Leu Trp Cys Gln Arg Lys 165 170 175 Thr Ala Pro Tyr Lys Asn Val Asn Val Gln Asn Phe His Ile Ser Trp 180 185 190 Lys Asp Gly Leu Ala Phe Asn Ala Leu Ile His Arg His Arg Pro Glu 195 200 205 Leu Ile Glu Tyr Asp Lys Leu Arg Lys Asp Asp Pro Val Thr Asn Leu 210 215 220 Asn Asn Ala Phe Glu Val Ala Glu Lys Tyr Leu Asp Ile Pro Lys Met 225 230 235 240 Leu Asp Ala Glu Asp Ile Val Asn Thr Ala Arg Pro Asp Glu Lys Ala 245 250 255 Ile Met Thr Tyr Val Ser Ser Phe Tyr His Ala Phe Ser Gly Ala Gln 260 265 270 Lys Ala Glu Thr Ala Ala Asn Arg Ile Cys Lys Val Leu Ala Val Asn 275 280 285 Gln Glu Asn Glu His Leu Met Glu Asp Tyr Glu Lys Leu Ala Ser Asp 290 295 300 Leu Leu Glu Trp Ile Arg Arg Thr Ile Pro Trp Leu Glu Asp Arg Val 305 310 315 320 Pro Gln Lys Thr Ile Gln Glu Met Gln Gln Lys Leu Glu Asp Phe Arg 325 330 335 Asp Tyr Arg Arg Val His Lys Pro Pro Lys Val Gln Glu Lys Cys Gln 340 345 350 Leu Glu Ile Asn Phe Asn Thr Leu Gln Thr Lys Leu Arg Leu Ser Asn 355 360 365 Arg Pro Ala Phe Met Pro Ser Glu Gly Lys Met Val Ser Asp Ile Asn 370 375 380 Asn Gly Trp Gln His Leu Glu Gln Ala Glu Lys Gly Tyr Glu Glu Trp 385 390 395 400 Leu Leu Asn Glu Ile Arg Arg Leu Glu Arg Leu Asp His Leu Ala Glu 405 410 415 Lys Phe Arg Gln Lys Ala Ser Ile His Glu Ala Trp Thr Asp Gly Lys 420 425 430 Glu Ala Met Leu Lys His Arg Asp Tyr Glu Thr Ala Thr Leu Ser Asp 435 440 445 Ile Lys Ala Leu Ile Arg Lys His Glu Ala Phe Glu Ser Asp Leu Ala 450 455 460 Ala His Gln Asp Arg Val Glu Gln Ile Ala Ala Ile Ala Gln Glu Leu 465 470 475 480 Asn Glu Leu Asp Tyr Tyr Asp Ser His Asn Val Asn Thr Arg Cys Gln 485 490 495 Lys Ile Cys Asp Gln Trp Asp Ala Leu Gly Ser Leu Thr His Ser Arg 500 505 510 Arg Glu Ala Leu Glu Lys Thr Glu Lys Gln Leu Glu Ala Ile Asp Gln 515 520 525 Leu His Leu Glu Tyr Ala Lys Arg Ala Ala Pro Phe Asn Asn Trp Met 530 535 540 Glu Ser Ala Met Glu Asp Leu Gln Asp Met Phe Ile Val His Thr Ile 545 550 555 560 Glu Glu Ile Glu Gly Leu Ile Ser Ala His Asp Gln Phe Lys Ser Thr 565 570 575 Leu Pro Asp Ala Asp Arg Glu Arg Glu Ala Ile Leu Ala Ile His Lys 580 585 590 Glu Ala Gln Arg Ile Ala Glu Ser Asn His Ile Lys Leu Ser Gly Ser 595 600 605 Asn Pro Tyr Thr Thr Val Thr Pro Gln Ile Ile Asn Ser Lys Trp Glu 610 615 620 Lys Val Gln Gln Leu Val Pro Lys Arg Asp His Ala Leu Leu Glu Glu 625 630 635 640 Gln Ser Lys Gln Gln Ser Asn Glu His Leu Arg Arg Gln Phe Ala Ser 645 650 655 Gln Ala Asn Val Val Gly Pro Trp Ile Gln Thr Lys Met Glu Glu Ile 660 665 670 Gly Arg Ile Ser Ile Glu Met Asn Gly Thr Leu Glu Asp Gln Leu Ser 675 680 685 His Leu Lys Gln Tyr Glu Arg Ser Ile Val Asp Tyr Lys Pro Asn Leu 690 695 700 Asp Leu Leu Glu Gln Gln His Gln Leu Ile Gln Glu Ala Leu Ile Phe 705 710 715 720 Asp Asn Lys His Thr Asn Tyr Thr Met Glu His Ile Arg Val Gly Trp 725 730 735 Glu Gln Leu Leu Thr Thr Ile Ala Arg Thr Ile Asn Glu Val Glu Asn 740 745 750 Gln Ile Leu Thr Arg Asp Ala Lys Gly Ile Ser Gln Glu Gln Met Gln 755 760 765 Glu Phe Arg Ala Ser Phe Asn His Phe Asp Lys Asp His Gly Gly Ala 770 775 780 Leu Gly Pro Glu Glu Phe Lys Ala Cys Leu Ile Ser Leu Gly Tyr Asp 785 790 795 800 Val Glu Asn Asp Arg Gln Gly Glu Ala Glu Phe Asn Arg Ile Met Ser 805 810 815 Leu Val Asp Pro Asn His Ser Gly Leu Val Thr Phe Gln Ala Phe Ile 820 825 830 Asp Phe Met Ser Arg Glu Thr Thr Asp Thr Asp Thr Ala Asp Gln Val 835 840 845 Ile Ala Ser Phe Lys Val Leu Ala Gly Asp Lys Asn Phe Ile Thr Ala 850 855 860 Glu Glu Leu Arg Arg Glu Leu Pro Pro Asp Gln Ala Glu Tyr Cys Ile 865 870 875 880 Ala Arg Met Ala Pro Tyr Gln Gly Pro Asp Ala Val Pro Gly Ala Leu 885 890 895 Asp Tyr Lys Ser Phe Ser Thr Ala Leu Tyr Gly Glu Ser Asp Leu 900 905 910 <210> 17 <211> 235 <212> PRT <213> Homo sapiens <400> 17 Met Ala Trp Ile Pro Leu Phe Leu Gly Val Leu Ala Tyr Cys Thr Gly 1 5 10 15 Ser Val Ala Ser Tyr Glu Leu Thr Gln Pro Pro Ser Val Ser Val Ser 20 25 30 Pro Gly Gln Thr Ala Ser Ile Thr Cys Ser Gly Asp Lys Leu Gly Asp 35 40 45 Lys Tyr Ala Cys Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Val Leu 50 55 60 Val Ile Tyr Gln Asp Ser Lys Arg Pro Ser Gly Ile Pro Glu Arg Phe 65 70 75 80 Ser Gly Ser Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Gly Thr 85 90 95 Gln Ala Met Asp Glu Ala Asp Tyr Tyr Cys Gln Ala Trp Asp Ser Ser 100 105 110 Ala Ser Gly Pro Val Leu Val Phe Gly Thr Gly Thr Lys Val Thr Val 115 120 125 Leu Gly Gln Pro Lys Ala Asn Pro Thr Val Thr Leu Phe Pro Pro Ser 130 135 140 Ser Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser 145 150 155 160 Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Gly Ser 165 170 175 Pro Val Lys Ala Gly Val Glu Thr Thr Lys Pro Ser Lys Gln Ser Asn 180 185 190 Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp 195 200 205 Lys Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr 210 215 220 Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 225 230 235 <210> 18 <211> 106 <212> PRT <213> Homo sapiens <400> 18 Gly Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser 1 5 10 15 Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp 20 25 30 Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro 35 40 45 Ala Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn 50 55 60 Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys 65 70 75 80 Ser His Lys Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val 85 90 95 Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 100 105 <210> 19 <211> 138 <212> PRT <213> Homo sapiens <400> 19 Met Lys Phe Thr Thr Leu Leu Phe Leu Ala Ala Val Ala Gly Ala Leu 1 5 10 15 Val Tyr Ala Glu Asp Ala Ser Ser Asp Ser Thr Gly Ala Asp Pro Ala 20 25 30 Gln Glu Ala Gly Thr Ser Lys Pro Asn Glu Glu Ile Ser Gly Pro Ala 35 40 45 Glu Pro Ala Ser Pro Pro Glu Thr Thr Thr Thr Ala Gln Glu Thr Ser 50 55 60 Ala Ala Ala Val Gln Gly Thr Ala Lys Val Thr Ser Ser Arg Gln Glu 65 70 75 80 Leu Asn Pro Leu Lys Ser Ile Val Glu Lys Ser Ile Leu Leu Thr Glu 85 90 95 Gln Ala Leu Ala Lys Ala Gly Lys Gly Met His Gly Gly Val Pro Gly 100 105 110 Gly Lys Gln Phe Ile Glu Asn Gly Ser Glu Phe Ala Gln Lys Leu Leu 115 120 125 Lys Lys Phe Ser Leu Leu Lys Pro Trp Ala 130 135 <210> 20 <211> 206 <212> PRT <213> Homo sapiens <400> 20 Met Ala Val Lys Lys Ile Ala Ile Phe Gly Ala Thr Gly Gln Thr Gly 1 5 10 15 Leu Thr Thr Leu Ala Gln Ala Val Gln Ala Gly Tyr Glu Val Thr Val 20 25 30 Leu Val Arg Asp Ser Ser Arg Leu Pro Ser Glu Gly Pro Arg Pro Ala 35 40 45 His Val Val Val Gly Asp Val Leu Gln Ala Ala Asp Val Asp Lys Thr 50 55 60 Val Ala Gly Gln Asp Ala Val Ile Val Leu Leu Gly Thr Arg Asn Asp 65 70 75 80 Leu Ser Pro Thr Thr Val Met Ser Glu Gly Ala Arg Asn Ile Val Ala 85 90 95 Ala Met Lys Ala His Gly Val Asp Lys Val Val Ala Cys Thr Ser Ala 100 105 110 Phe Leu Leu Trp Asp Pro Thr Lys Val Pro Pro Arg Leu Gln Ala Val 115 120 125 Thr Asp Asp His Ile Arg Met His Lys Val Leu Arg Glu Ser Gly Leu 130 135 140 Lys Tyr Val Ala Val Met Pro Pro His Ile Gly Asp Gln Pro Leu Thr 145 150 155 160 Gly Ala Tyr Thr Val Thr Leu Asp Gly Arg Gly Pro Ser Arg Val Ile 165 170 175 Ser Lys His Asp Leu Gly His Phe Met Leu Arg Cys Leu Thr Thr Asp 180 185 190 Glu Tyr Asp Gly His Ser Thr Tyr Pro Ser His Gln Tyr Gln 195 200 205 <210> 21 <211> 396 <212> PRT <213> Homo sapiens <400> 21 Met Phe Leu Lys Ala Val Val Leu Thr Leu Ala Leu Val Ala Val Ala 1 5 10 15 Gly Ala Arg Ala Glu Val Ser Ala Asp Gln Val Ala Thr Val Met Trp 20 25 30 Asp Tyr Phe Ser Gln Leu Ser Asn Asn Ala Lys Glu Ala Val Glu His 35 40 45 Leu Gln Lys Ser Glu Leu Thr Gln Gln Leu Asn Ala Leu Phe Gln Asp 50 55 60 Lys Leu Gly Glu Val Asn Thr Tyr Ala Gly Asp Leu Gln Lys Lys Leu 65 70 75 80 Val Pro Phe Ala Thr Glu Leu His Glu Arg Leu Ala Lys Asp Ser Glu 85 90 95 Lys Leu Lys Glu Glu Ile Gly Lys Glu Leu Glu Glu Leu Arg Ala Arg 100 105 110 Leu Leu Pro His Ala Asn Glu Val Ser Gln Lys Ile Gly Asp Asn Leu 115 120 125 Arg Glu Leu Gln Gln Arg Leu Glu Pro Tyr Ala Asp Gln Leu Arg Thr 130 135 140 Gln Val Asn Thr Gln Ala Glu Gln Leu Arg Arg Gln Leu Thr Pro Tyr 145 150 155 160 Ala Gln Arg Met Glu Arg Val Leu Arg Glu Asn Ala Asp Ser Leu Gln 165 170 175 Ala Ser Leu Arg Pro His Ala Asp Glu Leu Lys Ala Lys Ile Asp Gln 180 185 190 Asn Val Glu Glu Leu Lys Gly Arg Leu Thr Pro Tyr Ala Asp Glu Phe 195 200 205 Lys Val Lys Ile Asp Gln Thr Val Glu Glu Leu Arg Arg Ser Leu Ala 210 215 220 Pro Tyr Ala Gln Asp Thr Gln Glu Lys Leu Asn His Gln Leu Glu Gly 225 230 235 240 Leu Thr Phe Gln Met Lys Lys Asn Ala Glu Glu Leu Lys Ala Arg Ile 245 250 255 Ser Ala Ser Ala Glu Glu Leu Arg Gln Arg Leu Ala Pro Leu Ala Glu 260 265 270 Asp Val Arg Gly Asn Leu Arg Gly Asn Thr Glu Gly Leu Gln Lys Ser 275 280 285 Leu Ala Glu Leu Gly Gly His Leu Asp Gln Gln Val Glu Glu Phe Arg 290 295 300 Arg Arg Val Glu Pro Tyr Gly Glu Asn Phe Asn Lys Ala Leu Val Gln 305 310 315 320 Gln Met Glu Gln Leu Arg Gln Lys Leu Gly Pro His Ala Gly Asp Val 325 330 335 Glu Gly His Leu Ser Phe Leu Glu Lys Asp Leu Arg Asp Lys Val Asn 340 345 350 Ser Phe Phe Ser Thr Phe Lys Glu Lys Glu Ser Gln Asp Lys Thr Leu 355 360 365 Ser Leu Pro Glu Leu Glu Gln Gln Gln Glu Gln Gln Gln Glu Gln Gln 370 375 380 Gln Glu Gln Val Gln Met Leu Ala Pro Leu Glu Ser 385 390 395 <210> 22 <211> 267 <212> PRT <213> Homo sapiens <400> 22 Met Lys Ala Ala Val Leu Thr Leu Ala Val Leu Phe Leu Thr Gly Ser 1 5 10 15 Gln Ala Arg His Phe Trp Gln Gln Asp Glu Pro Pro Gln Ser Pro Trp 20 25 30 Asp Arg Val Lys Asp Leu Ala Thr Val Tyr Val Asp Val Leu Lys Asp 35 40 45 Ser Gly Arg Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala Leu Gly Lys 50 55 60 Gln Leu Asn Leu Lys Leu Leu Asp Asn Trp Asp Ser Val Thr Ser Thr 65 70 75 80 Phe Ser Lys Leu Arg Glu Gln Leu Gly Pro Val Thr Gln Glu Phe Trp 85 90 95 Asp Asn Leu Glu Lys Glu Thr Glu Gly Leu Arg Gln Glu Met Ser Lys 100 105 110 Asp Leu Glu Glu Val Lys Ala Lys Val Gln Pro Tyr Leu Asp Asp Phe 115 120 125 Gln Lys Lys Trp Gln Glu Glu Met Glu Leu Tyr Arg Gln Lys Val Glu 130 135 140 Pro Leu Arg Ala Glu Leu Gln Glu Gly Ala Arg Gln Lys Leu His Glu 145 150 155 160 Leu Gln Glu Lys Leu Ser Pro Leu Gly Glu Glu Met Arg Asp Arg Ala 165 170 175 Arg Ala His Val Asp Ala Leu Arg Thr His Leu Ala Pro Tyr Ser Asp 180 185 190 Glu Leu Arg Gln Arg Leu Ala Ala Arg Leu Glu Ala Leu Lys Glu Asn 195 200 205 Gly Gly Ala Arg Leu Ala Glu Tyr His Ala Lys Ala Thr Glu His Leu 210 215 220 Ser Thr Leu Ser Glu Lys Ala Lys Pro Ala Leu Glu Asp Leu Arg Gln 225 230 235 240 Gly Leu Leu Pro Val Leu Glu Ser Phe Lys Val Ser Phe Leu Ser Ala 245 250 255 Leu Glu Glu Tyr Thr Lys Lys Leu Asn Thr Gln 260 265 <210> 23 <211> 326 <212> PRT <213> Homo sapiens <400> 23 Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg 1 5 10 15 Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr 20 25 30 Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser 35 40 45 Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser 50 55 60 Leu Ser Ser Val Val Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr 65 70 75 80 Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys 85 90 95 Thr Val Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro 100 105 110 Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 115 120 125 Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 130 135 140 Val Ser His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly 145 150 155 160 Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn 165 170 175 Ser Thr Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp 180 185 190 Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro 195 200 205 Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu 210 215 220 Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn 225 230 235 240 Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 245 250 255 Ser Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 260 265 270 Thr Pro Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 275 280 285 Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 290 295 300 Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 305 310 315 320 Ser Leu Ser Pro Gly Lys 325 <210> 24 <211> 462 <212> PRT <213> Homo sapiens <400> 24 Met Ala Arg Val Leu Gly Ala Pro Val Ala Leu Gly Leu Trp Ser Leu 1 5 10 15 Cys Trp Ser Leu Ala Ile Ala Thr Pro Leu Pro Pro Thr Ser Ala His 20 25 30 Gly Asn Val Ala Glu Gly Glu Thr Lys Pro Asp Pro Asp Val Thr Glu 35 40 45 Arg Cys Ser Asp Gly Trp Ser Phe Asp Ala Thr Thr Leu Asp Asp Asn 50 55 60 Gly Thr Met Leu Phe Phe Lys Gly Glu Phe Val Trp Lys Ser His Lys 65 70 75 80 Trp Asp Arg Glu Leu Ile Ser Glu Arg Trp Lys Asn Phe Pro Ser Pro 85 90 95 Val Asp Ala Ala Phe Arg Gln Gly His Asn Ser Val Phe Leu Ile Lys 100 105 110 Gly Asp Lys Val Trp Val Tyr Pro Pro Glu Lys Lys Glu Lys Gly Tyr 115 120 125 Pro Lys Leu Leu Gln Asp Glu Phe Pro Gly Ile Pro Ser Pro Leu Asp 130 135 140 Ala Ala Val Glu Cys His Arg Gly Glu Cys Gln Ala Glu Gly Val Leu 145 150 155 160 Phe Phe Gln Gly Asp Arg Glu Trp Phe Trp Asp Leu Ala Thr Gly Thr 165 170 175 Met Lys Glu Arg Ser Trp Pro Ala Val Gly Asn Cys Ser Ser Ala Leu 180 185 190 Arg Trp Leu Gly Arg Tyr Tyr Cys Phe Gln Gly Asn Gln Phe Leu Arg 195 200 205 Phe Asp Pro Val Arg Gly Glu Val Pro Pro Arg Tyr Pro Arg Asp Val 210 215 220 Arg Asp Tyr Phe Met Pro Cys Pro Gly Arg Gly His Gly His Arg Asn 225 230 235 240 Gly Thr Gly His Gly Asn Ser Thr His His Gly Pro Glu Tyr Met Arg 245 250 255 Cys Ser Pro His Leu Val Leu Ser Ala Leu Thr Ser Asp Asn His Gly 260 265 270 Ala Thr Tyr Ala Phe Ser Gly Thr His Tyr Trp Arg Leu Asp Thr Ser 275 280 285 Arg Asp Gly Trp His Ser Trp Pro Ile Ala His Gln Trp Pro Gln Gly 290 295 300 Pro Ser Ala Val Asp Ala Ala Phe Ser Trp Glu Glu Lys Leu Tyr Leu 305 310 315 320 Val Gln Gly Thr Gln Val Tyr Val Phe Leu Thr Lys Gly Gly Tyr Thr 325 330 335 Leu Val Ser Gly Tyr Pro Lys Arg Leu Glu Lys Glu Val Gly Thr Pro 340 345 350 His Gly Ile Ile Leu Asp Ser Val Asp Ala Ala Phe Ile Cys Pro Gly 355 360 365 Ser Ser Arg Leu His Ile Met Ala Gly Arg Arg Leu Trp Trp Leu Asp 370 375 380 Leu Lys Ser Gly Ala Gln Ala Thr Trp Thr Glu Leu Pro Trp Pro His 385 390 395 400 Glu Lys Val Asp Gly Ala Leu Cys Met Glu Lys Ser Leu Gly Pro Asn 405 410 415 Ser Cys Ser Ala Asn Gly Pro Gly Leu Tyr Leu Ile His Gly Pro Asn 420 425 430 Leu Tyr Cys Tyr Ser Asp Val Glu Lys Leu Asn Ala Ala Lys Ala Leu 435 440 445 Pro Gln Pro Gln Asn Val Thr Ser Leu Leu Gly Cys Thr His 450 455 460 <210> 25 <211> 583 <212> PRT <213> Homo sapiens <400> 25 Met Ala His Val Arg Gly Leu Gln Leu Pro Gly Cys Leu Ala Leu Ala 1 5 10 15 Ala Leu Cys Ser Leu Val His Ser Gln His Val Phe Leu Ala Pro Gln 20 25 30 Gln Ala Arg Ser Leu Leu Gln Arg Val Arg Arg Ala Asn Thr Phe Leu 35 40 45 Glu Glu Val Arg Lys Gly Asn Leu Glu Arg Glu Cys Val Glu Glu Thr 50 55 60 Cys Ser Tyr Glu Glu Ala Phe Glu Ala Leu Glu Ser Ser Thr Ala Thr 65 70 75 80 Asp Val Phe Trp Ala Lys Tyr Thr Ala Cys Glu Thr Ala Arg Thr Pro 85 90 95 Arg Asp Lys Leu Ala Ala Cys Leu Glu Gly Asn Cys Ala Glu Gly Leu 100 105 110 Gly Thr Asn Tyr Arg Gly His Val Asn Ile Thr Arg Ser Gly Ile Glu 115 120 125 Cys Gln Leu Trp Arg Ser Arg Tyr Pro His Lys Pro Glu Ile Asn Ser 130 135 140 Thr Thr His Pro Gly Ala Asp Leu Gln Glu Asn Phe Cys Arg Asn Pro 145 150 155 160 Asp Ser Ser Thr Thr Gly Pro Trp Cys Tyr Thr Thr Asp Pro Thr Val 165 170 175 Arg Arg Gln Glu Cys Ser Ile Pro Val Cys Gly Gln Asp Gln Val Thr 180 185 190 Val Ala Met Thr Pro Arg Ser Glu Gly Ser Ser Val Asn Leu Ser Pro 195 200 205 Pro Leu Glu Gln Cys Val Pro Asp Arg Gly Gln Gln Tyr Gln Gly Arg 210 215 220 Leu Ala Val Thr Thr His Gly Leu Pro Cys Leu Ala Trp Ala Ser Ala 225 230 235 240 Gln Ala Lys Ala Leu Ser Lys His Gln Asp Phe Asn Ser Ala Val Gln 245 250 255 Leu Val Glu Asn Phe Cys Arg Asn Pro Asp Gly Asp Glu Glu Gly Val 260 265 270 Trp Cys Tyr Val Ala Gly Lys Pro Gly Asp Phe Gly Tyr Cys Asp Leu 275 280 285 Asn Tyr Cys Glu Glu Ala Val Glu Glu Glu Thr Gly Asp Gly Leu Asp 290 295 300 Glu Asp Ser Asp Arg Ala Ile Glu Gly Arg Thr Ala Thr Ser Glu Tyr 305 310 315 320 Gln Thr Phe Phe Asn Pro Arg Thr Phe Gly Ser Gly Glu Ala Asp Cys 325 330 335 Gly Leu Arg Pro Leu Phe Glu Lys Lys Ser Leu Glu Asp Lys Thr Glu 340 345 350 Arg Glu Leu Leu Glu Ser Tyr Ile Asp Gly Arg Ile Val Glu Gly Ser 355 360 365 Asp Ala Glu Ile Gly Met Ser Pro Trp Gln Val Met Leu Phe Arg Lys 370 375 380 Ser Pro Gln Glu Leu Leu Cys Gly Ala Ser Leu Ile Ser Asp Arg Trp 385 390 395 400 Val Leu Thr Ala Ala His Cys Leu Leu Tyr Pro Pro Trp Asp Lys Asn 405 410 415 Phe Thr Glu Asn Asp Leu Leu Val Arg Ile Gly Lys His Ser Arg Thr 420 425 430 Arg Tyr Glu Arg Asn Ile Glu Lys Ile Ser Met Leu Glu Lys Ile Tyr 435 440 445 Ile His Pro Ser Leu Leu Gln Ala Gly Tyr Lys Gly Arg Val Thr Gly 450 455 460 Trp Gly Asn Leu Lys Glu Thr Trp Thr Ala Asn Val Gly Lys Gly Gln 465 470 475 480 Pro Ser Val Leu Gln Val Val Asn Leu Pro Ile Val Glu Arg Pro Val 485 490 495 Cys Lys Asp Ser Thr Arg Ile Arg Ile Thr Asp Asn Met Phe Cys Ala 500 505 510 Gly Tyr Lys Pro Asp Glu Gly Lys Arg Gly Asp Ala Cys Glu Gly Asp 515 520 525 Ser Gly Gly Pro Phe Val Met Lys Ser Pro Phe Asn Asn Arg Trp Tyr 530 535 540 Gln Met Gly Ile Val Ser Trp Gly Glu Gly Cys Asp Arg Asp Gly Lys 545 550 555 560 Tyr Gly Phe Tyr Thr His Val Phe Arg Leu Lys Lys Trp Ile Gln Lys 565 570 575 Val Ile Asp Gln Phe Gly Glu 580 <210> 26 <211> 111 <212> PRT <213> Homo sapiens <400> 26 Tyr Val Leu Thr Gln Pro Pro Ser Val Ser Val Ala Pro Gly Glu Thr 1 5 10 15 Ala Arg Leu Thr Cys Gly Gly Asn Asp Ile Gly Ser Glu Ser Val His 20 25 30 Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr Phe 35 40 45 Asp Arg Asp Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser Asn 50 55 60 Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Val Glu Ala Gly Asp 65 70 75 80 Glu Ala Asp Tyr Tyr Cys Gln Leu Trp Asp Ser Ser Ser Glu His Val 85 90 95 Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Ser Gln Pro Lys 100 105 110 <210> 27 <211> 140 <212> PRT <213> Homo sapiens <400> 27 Met Ala Gly Trp Asn Ala Tyr Ile Asp Asn Leu Met Ala Asp Gly Thr 1 5 10 15 Cys Gln Asp Ala Ala Ile Val Gly Tyr Lys Asp Ser Pro Ser Val Trp 20 25 30 Ala Ala Val Pro Gly Lys Thr Phe Val Asn Ile Thr Pro Ala Glu Val 35 40 45 Gly Val Leu Val Gly Lys Asp Arg Ser Ser Phe Tyr Val Asn Gly Leu 50 55 60 Thr Leu Gly Gly Gln Lys Cys Ser Val Ile Arg Asp Ser Leu Leu Gln 65 70 75 80 Asp Gly Glu Phe Ser Met Asp Leu Arg Thr Lys Ser Thr Gly Gly Ala 85 90 95 Pro Thr Phe Asn Val Thr Val Thr Lys Thr Asp Lys Thr Leu Val Leu 100 105 110 Leu Met Gly Lys Glu Gly Val His Gly Gly Leu Ile Asn Lys Lys Cys 115 120 125 Tyr Glu Met Ala Ser His Leu Arg Arg Ser Gln Tyr 130 135 140 <210> 28 <211> 175 <212> PRT <213> Homo sapiens <400> 28 Met Glu Lys Ile Pro Val Ser Ala Phe Leu Leu Leu Val Ala Leu Ser 1 5 10 15 Tyr Thr Leu Ala Arg Asp Thr Thr Val Lys Pro Gly Ala Lys Lys Asp 20 25 30 Thr Lys Asp Ser Arg Pro Lys Leu Pro Gln Thr Leu Ser Arg Gly Trp 35 40 45 Gly Asp Gln Leu Ile Trp Thr Gln Thr Tyr Glu Glu Ala Leu Tyr Lys 50 55 60 Ser Lys Thr Ser Asn Lys Pro Leu Met Ile Ile His His Leu Asp Glu 65 70 75 80 Cys Pro His Ser Gln Ala Leu Lys Lys Val Phe Ala Glu Asn Lys Glu 85 90 95 Ile Gln Lys Leu Ala Glu Gln Phe Val Leu Leu Asn Leu Val Tyr Glu 100 105 110 Thr Thr Asp Lys His Leu Ser Pro Asp Gly Gln Tyr Val Pro Arg Ile 115 120 125 Met Phe Val Asp Pro Ser Leu Thr Val Arg Ala Asp Ile Thr Gly Arg 130 135 140 Tyr Ser Asn Arg Leu Tyr Ala Tyr Glu Pro Ala Asp Thr Ala Leu Leu 145 150 155 160 Leu Asp Asn Met Lys Lys Ala Leu Lys Leu Leu Lys Thr Glu Leu 165 170 175 <210> 29 <211> 147 <212> PRT <213> Homo sapiens <400> 29 Met Ser Glu Glu Lys Pro Lys Glu Gly Val Lys Thr Glu Asn Asp His 1 5 10 15 Ile Asn Leu Lys Val Ala Gly Gln Asp Gly Ser Val Val Gln Phe Lys 20 25 30 Ile Lys Arg His Thr Pro Leu Ser Lys Leu Met Lys Ala Tyr Cys Glu 35 40 45 Arg Gln Gly Leu Ser Met Arg Gln Ile Arg Phe Arg Phe Asp Gly Gln 50 55 60 Pro Ile Asn Glu Thr Asp Thr Pro Ala Gln Gly Ile Ile Leu Ser Trp 65 70 75 80 Lys Glu Leu Trp Thr Trp Lys Gln Thr Phe Phe Phe Glu Thr Glu Ser 85 90 95 Arg Phe Val Ala Gln Ala Arg Met Gln Trp Arg Ser Leu Ser Ser Leu 100 105 110 Cys Lys Leu Cys Leu Leu Ser Ser Arg His Ser Pro Ala Ser Ala Ser 115 120 125 Gln Val Ala Gly Thr Ile Gly Ala His His His Ser Arg Leu Ile Phe 130 135 140 Leu Tyr Phe 145 <210> 30 <211> 347 <212> PRT <213> Homo sapiens <400> 30 Met Ser Ser Trp Ser Arg Gln Arg Pro Lys Ser Pro Gly Gly Ile Gln 1 5 10 15 Pro His Val Ser Arg Thr Leu Phe Leu Leu Leu Leu Leu Ala Ala Ser 20 25 30 Ala Trp Gly Val Thr Leu Ser Pro Lys Asp Cys Gln Val Phe Arg Ser 35 40 45 Asp His Gly Ser Ser Ile Ser Cys Gln Pro Pro Ala Glu Ile Pro Gly 50 55 60 Tyr Leu Pro Ala Asp Thr Val His Leu Ala Val Glu Phe Phe Asn Leu 65 70 75 80 Thr His Leu Pro Ala Asn Leu Leu Gln Gly Ala Ser Lys Leu Gln Glu 85 90 95 Leu His Leu Ser Ser Asn Gly Leu Glu Ser Leu Ser Pro Glu Phe Leu 100 105 110 Arg Pro Val Pro Gln Leu Arg Val Leu Asp Leu Thr Arg Asn Ala Leu 115 120 125 Thr Gly Leu Pro Pro Gly Leu Phe Gln Ala Ser Ala Thr Leu Asp Thr 130 135 140 Leu Val Leu Lys Glu Asn Gln Leu Glu Val Leu Glu Val Ser Trp Leu 145 150 155 160 His Gly Leu Lys Ala Leu Gly His Leu Asp Leu Ser Gly Asn Arg Leu 165 170 175 Arg Lys Leu Pro Pro Gly Leu Leu Ala Asn Phe Thr Leu Leu Arg Thr 180 185 190 Leu Asp Leu Gly Glu Asn Gln Leu Glu Thr Leu Pro Pro Asp Leu Leu 195 200 205 Arg Gly Pro Leu Gln Leu Glu Arg Leu His Leu Glu Gly Asn Lys Leu 210 215 220 Gln Val Leu Gly Lys Asp Leu Leu Leu Pro Gln Pro Asp Leu Arg Tyr 225 230 235 240 Leu Phe Leu Asn Gly Asn Lys Leu Ala Arg Val Ala Ala Gly Ala Phe 245 250 255 Gln Gly Leu Arg Gln Leu Asp Met Leu Asp Leu Ser Asn Asn Ser Leu 260 265 270 Ala Ser Val Pro Glu Gly Leu Trp Ala Ser Leu Gly Gln Pro Asn Trp 275 280 285 Asp Met Arg Asp Gly Phe Asp Ile Ser Gly Asn Pro Trp Ile Cys Asp 290 295 300 Gln Asn Leu Ser Asp Leu Tyr Arg Trp Leu Gln Ala Gln Lys Asp Lys 305 310 315 320 Met Phe Ser Gln Asn Asp Thr Arg Cys Ala Gly Pro Glu Ala Val Lys 325 330 335 Gly Gln Thr Leu Leu Ala Val Ala Lys Ser Gln 340 345 <210> 31 <211> 495 <212> PRT <213> Homo sapiens <400> 31 Met Ser Met Leu Val Val Phe Leu Leu Leu Trp Gly Val Thr Trp Gly 1 5 10 15 Pro Val Thr Glu Ala Ala Ile Phe Tyr Glu Thr Gln Pro Ser Leu Trp 20 25 30 Ala Glu Ser Glu Ser Leu Leu Lys Pro Leu Ala Asn Val Thr Leu Thr 35 40 45 Cys Gln Ala His Leu Glu Thr Pro Asp Phe Gln Leu Phe Lys Asn Gly 50 55 60 Val Ala Gln Glu Pro Val His Leu Asp Ser Pro Ala Ile Lys His Gln 65 70 75 80 Phe Leu Leu Thr Gly Asp Thr Gln Gly Arg Tyr Arg Cys Arg Ser Gly 85 90 95 Leu Ser Thr Gly Trp Thr Gln Leu Ser Lys Leu Leu Glu Leu Thr Gly 100 105 110 Pro Lys Ser Leu Pro Ala Pro Trp Leu Ser Met Ala Pro Val Ser Trp 115 120 125 Ile Thr Pro Gly Leu Lys Thr Thr Ala Val Cys Arg Gly Val Leu Arg 130 135 140 Gly Val Thr Phe Leu Leu Arg Arg Glu Gly Asp His Glu Phe Leu Glu 145 150 155 160 Val Pro Glu Ala Gln Glu Asp Val Glu Ala Thr Phe Pro Val His Gln 165 170 175 Pro Gly Asn Tyr Ser Cys Ser Tyr Arg Thr Asp Gly Glu Gly Ala Leu 180 185 190 Ser Glu Pro Ser Ala Thr Val Thr Ile Glu Glu Leu Ala Ala Pro Pro 195 200 205 Pro Pro Val Leu Met His His Gly Glu Ser Ser Gln Val Leu His Pro 210 215 220 Gly Asn Lys Val Thr Leu Thr Cys Val Ala Pro Leu Ser Gly Val Asp 225 230 235 240 Phe Gln Leu Arg Arg Gly Glu Lys Glu Leu Leu Val Pro Arg Ser Ser 245 250 255 Thr Ser Pro Asp Arg Ile Phe Phe His Leu Asn Ala Val Ala Leu Gly 260 265 270 Asp Gly Gly His Tyr Thr Cys Arg Tyr Arg Leu His Asp Asn Gln Asn 275 280 285 Gly Trp Ser Gly Asp Ser Ala Pro Val Glu Leu Ile Leu Ser Asp Glu 290 295 300 Thr Leu Pro Ala Pro Glu Phe Ser Pro Glu Pro Glu Ser Gly Arg Ala 305 310 315 320 Leu Arg Leu Arg Cys Leu Ala Pro Leu Glu Gly Ala Arg Phe Ala Leu 325 330 335 Val Arg Glu Asp Arg Gly Gly Arg Arg Val His Arg Phe Gln Ser Pro 340 345 350 Ala Gly Thr Glu Ala Leu Phe Glu Leu His Asn Ile Ser Val Ala Asp 355 360 365 Ser Ala Asn Tyr Ser Cys Val Tyr Val Asp Leu Lys Pro Pro Phe Gly 370 375 380 Gly Ser Ala Pro Ser Glu Arg Leu Glu Leu His Val Asp Gly Pro Pro 385 390 395 400 Pro Arg Pro Gln Leu Arg Ala Thr Trp Ser Gly Ala Val Leu Ala Gly 405 410 415 Arg Asp Ala Val Leu Arg Cys Glu Gly Pro Ile Pro Asp Val Thr Phe 420 425 430 Glu Leu Leu Arg Glu Gly Glu Thr Lys Ala Val Lys Thr Val Arg Thr 435 440 445 Pro Gly Ala Ala Ala Asn Leu Glu Leu Ile Phe Val Gly Pro Gln His 450 455 460 Ala Gly Asn Tyr Arg Cys Arg Tyr Arg Ser Trp Val Pro His Thr Phe 465 470 475 480 Glu Ser Glu Leu Ser Asp Pro Val Glu Leu Leu Val Ala Glu Ser 485 490 495 <210> 32 <211> 418 <212> PRT <213> Homo sapiens <400> 32 Met Pro Ser Ser Val Ser Trp Gly Ile Leu Leu Leu Ala Gly Leu Cys 1 5 10 15 Cys Leu Val Pro Val Ser Leu Ala Glu Asp Pro Gln Gly Asp Ala Ala 20 25 30 Gln Lys Thr Asp Thr Ser His His Asp Gln Asp His Pro Thr Phe Asn 35 40 45 Lys Ile Thr Pro Asn Leu Ala Glu Phe Ala Phe Ser Leu Tyr Arg Gln 50 55 60 Leu Ala His Gln Ser Asn Ser Thr Asn Ile Phe Phe Ser Pro Val Ser 65 70 75 80 Ile Ala Thr Ala Phe Ala Met Leu Ser Leu Gly Thr Lys Ala Asp Thr 85 90 95 His Asp Glu Ile Leu Glu Gly Leu Asn Phe Asn Leu Thr Glu Ile Pro 100 105 110 Glu Ala Gln Ile His Glu Gly Phe Gln Glu Leu Leu Arg Thr Leu Asn 115 120 125 Gln Pro Asp Ser Gln Leu Gln Leu Thr Thr Gly Asn Gly Leu Phe Leu 130 135 140 Ser Glu Gly Leu Lys Leu Val Asp Lys Phe Leu Glu Asp Val Lys Lys 145 150 155 160 Leu Tyr His Ser Glu Ala Phe Thr Val Asn Phe Gly Asp Thr Glu Glu 165 170 175 Ala Lys Lys Gln Ile Asn Asp Tyr Val Glu Lys Gly Thr Gln Gly Lys 180 185 190 Ile Val Asp Leu Val Lys Glu Leu Asp Arg Asp Thr Val Phe Ala Leu 195 200 205 Val Asn Tyr Ile Phe Phe Lys Gly Lys Trp Glu Arg Pro Phe Glu Val 210 215 220 Lys Asp Thr Glu Glu Glu Asp Phe His Val Asp Gln Val Thr Thr Val 225 230 235 240 Lys Val Pro Met Met Lys Arg Leu Gly Met Phe Asn Ile Gln His Cys 245 250 255 Lys Lys Leu Ser Ser Trp Val Leu Leu Met Lys Tyr Leu Gly Asn Ala 260 265 270 Thr Ala Ile Phe Phe Leu Pro Asp Glu Gly Lys Leu Gln His Leu Glu 275 280 285 Asn Glu Leu Thr His Asp Ile Ile Thr Lys Phe Leu Glu Asn Glu Asp 290 295 300 Arg Arg Ser Ala Ser Leu His Leu Pro Lys Leu Ser Ile Thr Gly Thr 305 310 315 320 Tyr Asp Leu Lys Ser Val Leu Gly Gln Leu Gly Ile Thr Lys Val Phe 325 330 335 Ser Asn Gly Ala Asp Leu Ser Gly Val Thr Glu Glu Ala Pro Leu Lys 340 345 350 Leu Ser Lys Ala Val His Lys Ala Val Leu Thr Ile Asp Glu Lys Gly 355 360 365 Thr Glu Ala Ala Gly Ala Met Phe Leu Glu Ala Ile Pro Met Ser Ile 370 375 380 Pro Pro Glu Val Lys Phe Asn Lys Pro Phe Val Phe Leu Met Ile Glu 385 390 395 400 Gln Asn Thr Lys Ser Pro Leu Phe Met Gly Lys Val Val Asn Pro Thr 405 410 415 Gln Lys <210> 33 <211> 146 <212> PRT <213> Homo sapiens <400> 33 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 Lys 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> 34 <211> 338 <212> PRT <213> Homo sapiens <400> 34 Met Leu Ser Ala Leu Ala Arg Pro Ala Ser Ala Ala Leu Arg Arg Ser 1 5 10 15 Phe Ser Thr Ser Ala Gln Asn Asn Ala Lys Val Ala Val Leu Gly Ala 20 25 30 Ser Gly Gly Ile Gly Gln Pro Leu Ser Leu Leu Leu Lys Asn Ser Pro 35 40 45 Leu Val Ser Arg Leu Thr Leu Tyr Asp Ile Ala His Thr Pro Gly Val 50 55 60 Ala Ala Asp Leu Ser His Ile Glu Thr Lys Ala Ala Val Lys Gly Tyr 65 70 75 80 Leu Gly Pro Glu Gln Leu Pro Asp Cys Leu Lys Gly Cys Asp Val Val 85 90 95 Val Ile Pro Ala Gly Val Pro Arg Lys Pro Gly Met Thr Arg Asp Asp 100 105 110 Leu Phe Asn Thr Asn Ala Thr Ile Val Ala Thr Leu Thr Ala Ala Cys 115 120 125 Ala Gln His Cys Pro Glu Ala Met Ile Cys Val Ile Ala Asn Pro Val 130 135 140 Asn Ser Thr Ile Pro Ile Thr Ala Glu Val Phe Lys Lys His Gly Val 145 150 155 160 Tyr Asn Pro Asn Lys Ile Phe Gly Val Thr Thr Leu Asp Ile Val Arg 165 170 175 Ala Asn Thr Phe Val Ala Glu Leu Lys Gly Leu Asp Pro Ala Arg Val 180 185 190 Asn Val Pro Val Ile Gly Gly His Ala Gly Lys Thr Ile Ile Pro Leu 195 200 205 Ile Ser Gln Cys Thr Pro Lys Val Asp Phe Pro Gln Asp Gln Leu Thr 210 215 220 Ala Leu Thr Gly Arg Ile Gln Glu Ala Gly Thr Glu Val Val Lys Ala 225 230 235 240 Lys Ala Gly Ala Gly Ser Ala Thr Leu Ser Met Ala Tyr Ala Gly Ala 245 250 255 Arg Phe Val Phe Ser Leu Val Asp Ala Met Asn Gly Lys Glu Gly Val 260 265 270 Val Glu Cys Ser Phe Val Lys Ser Gln Glu Thr Glu Cys Thr Tyr Phe 275 280 285 Ser Thr Pro Leu Leu Leu Gly Lys Lys Gly Ile Glu Lys Asn Leu Gly 290 295 300 Ile Gly Lys Val Ser Ser Phe Glu Glu Lys Met Ile Ser Asp Ala Ile 305 310 315 320 Pro Glu Leu Lys Ala Ser Ile Lys Lys Gly Glu Asp Phe Val Lys Thr 325 330 335 Leu Lys <210> 35 <211> 320 <212> PRT <213> Homo sapiens <400> 35 Met Ala Gln Val Leu Arg Gly Thr Val Thr Asp Phe Pro Gly Phe Asp 1 5 10 15 Glu Arg Ala Asp Ala Glu Thr Leu Arg Lys Ala Met Lys Gly Leu Gly 20 25 30 Thr Asp Glu Glu Ser Ile Leu Thr Leu Leu Thr Ser Arg Ser Asn Ala 35 40 45 Gln Arg Gln Glu Ile Ser Ala Ala Phe Lys Thr Leu Phe Gly Arg Asp 50 55 60 Leu Leu Asp Asp Leu Lys Ser Glu Leu Thr Gly Lys Phe Glu Lys Leu 65 70 75 80 Ile Val Ala Leu Met Lys Pro Ser Arg Leu Tyr Asp Ala Tyr Glu Leu 85 90 95 Lys His Ala Leu Lys Gly Ala Gly Thr Asn Glu Lys Val Leu Thr Glu 100 105 110 Ile Ile Ala Ser Arg Thr Pro Glu Glu Leu Arg Ala Ile Lys Gln Val 115 120 125 Tyr Glu Glu Glu Tyr Gly Ser Ser Leu Glu Asp Asp Val Val Gly Asp 130 135 140 Thr Ser Gly Tyr Tyr Gln Arg Met Leu Val Val Leu Leu Gln Ala Asn 145 150 155 160 Arg Asp Pro Asp Ala Gly Ile Asp Glu Ala Gln Val Glu Gln Asp Ala 165 170 175 Gln Ala Leu Phe Gln Ala Gly Glu Leu Lys Trp Gly Thr Asp Glu Glu 180 185 190 Lys Phe Ile Thr Ile Phe Gly Thr Arg Ser Val Ser His Leu Arg Lys 195 200 205 Val Phe Asp Lys Tyr Met Thr Ile Ser Gly Phe Gln Ile Glu Glu Thr 210 215 220 Ile Asp Arg Glu Thr Ser Gly Asn Leu Glu Gln Leu Leu Leu Ala Val 225 230 235 240 Val Lys Ser Ile Arg Ser Ile Pro Ala Tyr Leu Ala Glu Thr Leu Tyr 245 250 255 Tyr Ala Met Lys Gly Ala Gly Thr Asp Asp His Thr Leu Ile Arg Val 260 265 270 Met Val Ser Arg Ser Glu Ile Asp Leu Phe Asn Ile Arg Lys Glu Phe 275 280 285 Arg Lys Asn Phe Ala Thr Ser Leu Tyr Ser Met Ile Lys Gly Asp Thr 290 295 300 Ser Gly Asp Tyr Lys Lys Ala Leu Leu Leu Leu Cys Gly Glu Asp Asp 305 310 315 320 <210> 36 <211> 474 <212> PRT <213> Homo sapiens <400> 36 Met Ala Thr Asn Trp Gly Ser Leu Leu Gln Asp Lys Gln Gln Leu Glu 1 5 10 15 Glu Leu Ala Arg Gln Ala Val Asp Arg Ala Leu Ala Glu Gly Val Leu 20 25 30 Leu Arg Thr Ser Gln Glu Pro Thr Ser Ser Glu Val Val Ser Tyr Ala 35 40 45 Pro Phe Thr Leu Phe Pro Ser Leu Val Pro Ser Ala Leu Leu Glu Gln 50 55 60 Ala Tyr Ala Val Gln Met Asp Phe Asn Leu Leu Val Asp Ala Val Ser 65 70 75 80 Gln Asn Ala Ala Phe Leu Glu Gln Thr Leu Ser Ser Thr Ile Lys Gln 85 90 95 Asp Asp Phe Thr Ala Arg Leu Phe Asp Ile His Lys Gln Val Leu Lys 100 105 110 Glu Gly Ile Ala Gln Thr Val Phe Leu Gly Leu Asn Arg Ser Asp Tyr 115 120 125 Met Phe Gln Arg Ser Ala Asp Gly Ser Pro Ala Leu Lys Gln Ile Glu 130 135 140 Ile Asn Thr Ile Ser Ala Ser Phe Gly Gly Leu Ala Ser Arg Thr Pro 145 150 155 160 Ala Val His Arg His Val Leu Ser Val Leu Ser Lys Thr Lys Glu Ala 165 170 175 Gly Lys Ile Leu Ser Asn Asn Pro Ser Lys Gly Leu Ala Leu Gly Ile 180 185 190 Ala Lys Ala Trp Glu Leu Tyr Gly Ser Pro Asn Ala Leu Val Leu Leu 195 200 205 Ile Ala Gln Glu Lys Glu Arg Asn Ile Phe Asp Gln Arg Ala Ile Glu 210 215 220 Asn Glu Leu Leu Ala Arg Asn Ile His Val Ile Arg Arg Thr Phe Glu 225 230 235 240 Asp Ile Ser Glu Lys Gly Ser Leu Asp Gln Asp Arg Arg Leu Phe Val 245 250 255 Asp Gly Gln Glu Ile Ala Val Val Tyr Phe Arg Asp Gly Tyr Met Pro 260 265 270 Arg Gln Tyr Ser Leu Gln Asn Trp Glu Ala Arg Leu Leu Leu Glu Arg 275 280 285 Ser His Ala Ala Lys Cys Pro Asp Ile Ala Thr Gln Leu Ala Gly Thr 290 295 300 Lys Lys Val Gln Gln Glu Leu Ser Arg Pro Gly Met Leu Glu Met Leu 305 310 315 320 Leu Pro Gly Gln Pro Glu Ala Val Ala Arg Leu Arg Ala Thr Phe Ala 325 330 335 Gly Leu Tyr Ser Leu Asp Val Gly Glu Glu Gly Asp Gln Ala Ile Ala 340 345 350 Glu Ala Leu Ala Ala Pro Ser Arg Phe Val Leu Lys Pro Gln Arg Glu 355 360 365 Gly Gly Gly Asn Asn Leu Tyr Gly Glu Glu Met Val Gln Ala Leu Lys 370 375 380 Gln Leu Lys Asp Ser Glu Glu Arg Ala Ser Tyr Ile Leu Met Glu Lys 385 390 395 400 Ile Glu Pro Glu Pro Phe Glu Asn Cys Leu Leu Arg Pro Gly Ser Pro 405 410 415 Ala Arg Val Val Gln Cys Ile Ser Glu Leu Gly Ile Phe Gly Val Tyr 420 425 430 Val Arg Gln Glu Lys Thr Leu Val Met Asn Lys His Val Gly His Leu 435 440 445 Leu Arg Thr Lys Ala Ile Glu His Ala Asp Gly Gly Val Ala Ala Gly 450 455 460 Val Ala Val Leu Asp Asn Pro Tyr Pro Val 465 470 <210> 37 <211> 847 <212> PRT <213> Homo sapiens <400> 37 Met Ala Lys Pro Leu Thr Asp Gln Glu Lys Arg Arg Gln Ile Ser Ile 1 5 10 15 Arg Gly Ile Val Gly Val Glu Asn Val Ala Glu Leu Lys Lys Ser Phe 20 25 30 Asn Arg His Leu His Phe Thr Leu Val Lys Asp Arg Asn Val Ala Thr 35 40 45 Thr Arg Asp Tyr Tyr Phe Ala Leu Ala His Thr Val Arg Asp His Leu 50 55 60 Val Gly Arg Trp Ile Arg Thr Gln Gln His Tyr Tyr Asp Lys Cys Pro 65 70 75 80 Lys Arg Val Tyr Tyr Leu Ser Leu Glu Phe Tyr Met Gly Arg Thr Leu 85 90 95 Gln Asn Thr Met Ile Asn Leu Gly Leu Gln Asn Ala Cys Asp Glu Ala 100 105 110 Ile Tyr Gln Leu Gly Leu Asp Ile Glu Glu Leu Glu Glu Ile Glu Glu 115 120 125 Asp Ala Gly Leu Gly Asn Gly Gly Leu Gly Arg Leu Ala Ala Cys Phe 130 135 140 Leu Asp Ser Met Ala Thr Leu Gly Leu Ala Ala Tyr Gly Tyr Gly Ile 145 150 155 160 Arg Tyr Glu Tyr Gly Ile Phe Asn Gln Lys Ile Arg Asp Gly Trp Gln 165 170 175 Val Glu Glu Ala Asp Asp Trp Leu Arg Tyr Gly Asn Pro Trp Glu Lys 180 185 190 Ser Arg Pro Glu Phe Met Leu Pro Val His Phe Tyr Gly Lys Val Glu 195 200 205 His Thr Asn Thr Gly Thr Lys Trp Ile Asp Thr Gln Val Val Leu Ala 210 215 220 Leu Pro Tyr Asp Thr Pro Val Pro Gly Tyr Met Asn Asn Thr Val Asn 225 230 235 240 Thr Met Arg Leu Trp Ser Ala Arg Ala Pro Asn Asp Phe Asn Leu Arg 245 250 255 Asp Phe Asn Val Gly Asp Tyr Ile Gln Ala Val Leu Asp Arg Asn Leu 260 265 270 Ala Glu Asn Ile Ser Arg Val Leu Tyr Pro Asn Asp Asn Phe Phe Glu 275 280 285 Gly Lys Glu Leu Arg Leu Lys Gln Glu Tyr Phe Val Val Ala Ala Thr 290 295 300 Leu Gln Asp Ile Ile Arg Arg Phe Lys Ala Ser Lys Phe Gly Ser Thr 305 310 315 320 Arg Gly Ala Gly Thr Val Phe Asp Ala Phe Pro Asp Gln Val Ala Ile 325 330 335 Gln Leu Asn Asp Thr His Pro Ala Leu Ala Ile Pro Glu Leu Met Arg 340 345 350 Ile Phe Val Asp Ile Glu Lys Leu Pro Trp Ser Lys Ala Trp Glu Leu 355 360 365 Thr Gln Lys Thr Phe Ala Tyr Thr Asn His Thr Val Leu Pro Glu Ala 370 375 380 Leu Glu Arg Trp Pro Val Asp Leu Val Glu Lys Leu Leu Pro Arg His 385 390 395 400 Leu Glu Ile Ile Tyr Glu Ile Asn Gln Lys His Leu Asp Arg Ile Val 405 410 415 Ala Leu Phe Pro Lys Asp Val Asp Arg Leu Arg Arg Met Ser Leu Ile 420 425 430 Glu Glu Glu Gly Ser Lys Arg Ile Asn Met Ala His Leu Cys Ile Val 435 440 445 Gly Ser His Ala Val Asn Gly Val Ala Lys Ile His Ser Asp Ile Val 450 455 460 Lys Thr Lys Val Phe Lys Asp Phe Ser Glu Leu Glu Pro Asp Lys Phe 465 470 475 480 Gln Asn Lys Thr Asn Gly Ile Thr Pro Arg Arg Trp Leu Leu Leu Cys 485 490 495 Asn Pro Gly Leu Ala Glu Leu Ile Ala Glu Lys Ile Gly Glu Asp Tyr 500 505 510 Val Lys Asp Leu Ser Gln Leu Thr Lys Leu His Ser Phe Leu Gly Asp 515 520 525 Asp Val Phe Leu Arg Glu Leu Ala Lys Val Lys Gln Glu Asn Lys Leu 530 535 540 Lys Phe Ser Gln Phe Leu Glu Thr Glu Tyr Lys Val Lys Ile Asn Pro 545 550 555 560 Ser Ser Met Phe Asp Val Gln Val Lys Arg Ile His Glu Tyr Lys Arg 565 570 575 Gln Leu Leu Asn Cys Leu His Val Ile Thr Met Tyr Asn Arg Ile Lys 580 585 590 Lys Asp Pro Lys Lys Leu Phe Val Pro Arg Thr Val Ile Ile Gly Gly 595 600 605 Lys Ala Ala Pro Gly Tyr His Met Ala Lys Met Ile Ile Lys Leu Ile 610 615 620 Thr Ser Val Ala Asp Val Val Asn Asn Asp Pro Met Val Gly Ser Lys 625 630 635 640 Leu Lys Val Ile Phe Leu Glu Asn Tyr Arg Val Ser Leu Ala Glu Lys 645 650 655 Val Ile Pro Ala Thr Asp Leu Ser Glu Gln Ile Ser Thr Ala Gly Thr 660 665 670 Glu Ala Ser Gly Thr Gly Asn Met Lys Phe Met Leu Asn Gly Ala Leu 675 680 685 Thr Ile Gly Thr Met Asp Gly Ala Asn Val Glu Met Ala Glu Glu Ala 690 695 700 Gly Glu Glu Asn Leu Phe Ile Phe Gly Met Arg Ile Asp Asp Val Ala 705 710 715 720 Ala Leu Asp Lys Lys Gly Tyr Glu Ala Lys Glu Tyr Tyr Glu Ala Leu 725 730 735 Pro Glu Leu Lys Leu Val Ile Asp Gln Ile Asp Asn Gly Phe Phe Ser 740 745 750 Pro Lys Gln Pro Asp Leu Phe Lys Asp Ile Ile Asn Met Leu Phe Tyr 755 760 765 His Asp Arg Phe Lys Val Phe Ala Asp Tyr Glu Ala Tyr Val Lys Cys 770 775 780 Gln Asp Lys Val Ser Gln Leu Tyr Met Asn Pro Lys Ala Trp Asn Thr 785 790 795 800 Met Val Leu Lys Asn Ile Ala Ala Ser Gly Lys Phe Ser Ser Asp Arg 805 810 815 Thr Ile Lys Glu Tyr Ala Gln Asn Ile Trp Asn Val Glu Pro Ser Asp 820 825 830 Leu Lys Ile Ser Leu Ser Asn Glu Ser Asn Lys Val Asn Gly Asn 835 840 845 <210> 38 <211> 375 <212> PRT <213> Homo sapiens <400> 38 Met Ser Thr Ala Gly Lys Val Ile Lys Cys Lys Ala Ala Val Leu Trp 1 5 10 15 Glu Leu Lys Lys Pro Phe Ser Ile Glu Glu Val Glu Val Ala Pro Pro 20 25 30 Lys Ala His Glu Val Arg Ile Lys Met Val Ala Ala Gly Ile Cys Arg 35 40 45 Ser Asp Glu His Val Val Ser Gly Asn Leu Val Thr Pro Leu Pro Val 50 55 60 Ile Leu Gly His Glu Ala Ala Gly Ile Val Glu Ser Val Gly Glu Gly 65 70 75 80 Val Thr Thr Val Lys Pro Gly Asp Lys Val Ile Pro Leu Phe Thr Pro 85 90 95 Gln Cys Gly Lys Cys Arg Ile Cys Lys Asn Pro Glu Ser Asn Tyr Cys 100 105 110 Leu Lys Asn Asp Leu Gly Asn Pro Arg Gly Thr Leu Gln Asp Gly Thr 115 120 125 Arg Arg Phe Thr Cys Ser Gly Lys Pro Ile His His Phe Val Gly Val 130 135 140 Ser Thr Phe Ser Gln Tyr Thr Val Val Asp Glu Asn Ala Val Ala Lys 145 150 155 160 Ile Asp Ala Ala Ser Pro Leu Glu Lys Val Cys Leu Ile Gly Cys Gly 165 170 175 Phe Ser Thr Gly Tyr Gly Ser Ala Val Lys Val Ala Lys Val Thr Pro 180 185 190 Gly Ser Thr Cys Ala Val Phe Gly Leu Gly Gly Val Gly Leu Ser Val 195 200 205 Val Met Gly Cys Lys Ala Ala Gly Ala Ala Arg Ile Ile Ala Val Asp 210 215 220 Ile Asn Lys Asp Lys Phe Ala Lys Ala Lys Glu Leu Gly Ala Thr Glu 225 230 235 240 Cys Ile Asn Pro Gln Asp Tyr Lys Lys Pro Ile Gln Glu Val Leu Lys 245 250 255 Glu Met Thr Asp Gly Gly Val Asp Phe Ser Phe Glu Val Ile Gly Arg 260 265 270 Leu Asp Thr Met Met Ala Ser Leu Leu Cys Cys His Glu Ala Cys Gly 275 280 285 Thr Ser Val Ile Val Gly Val Pro Pro Asp Ser Gln Asn Leu Ser Ile 290 295 300 Asn Pro Met Leu Leu Leu Thr Gly Arg Thr Trp Lys Gly Ala Ile Phe 305 310 315 320 Gly Gly Phe Lys Ser Lys Glu Ser Val Pro Lys Leu Val Ala Asp Phe 325 330 335 Met Ala Lys Lys Phe Ser Leu Asp Ala Leu Ile Thr Asn Ile Leu Pro 340 345 350 Phe Glu Lys Ile Asn Glu Gly Phe Asp Leu Leu Arg Ser Gly Lys Ser 355 360 365 Ile Arg Thr Val Leu Thr Phe 370 375 <210> 39 <211> 1311 <212> PRT <213> Homo sapiens <220> <221> misc_feature <222> (1)..(1) <223> Xaa can be any naturally occurring amino acid <400> 39 Xaa Arg Glu Ile Val Thr Arg Asn Leu Ser Gln Pro Glu Ser Pro Val 1 5 10 15 Leu Leu Pro Ala Thr Glu Met Ala Ser Leu Leu Ser Leu Gln Glu Glu 20 25 30 Asn Gln Leu Leu Gln Gln Glu Leu Ser Arg Val Glu Asp Leu Leu Ala 35 40 45 Gln Ser Arg Ala Glu Arg Asp Glu Leu Ala Ile Lys Tyr Asn Ala Val 50 55 60 Ser Glu Arg Asp Thr Glu His Ser Gln Asp Leu Glu Ser Ala Leu Ile 65 70 75 80 Arg Leu Glu Glu Glu Gln Gln Arg Ser Ala Ser Leu Ala Gln Val Asn 85 90 95 Ala Met Leu Arg Glu Gln Leu Asp Gln Ala Gly Ser Ala Asn Gln Ala 100 105 110 Leu Ser Glu Asp Ile Arg Lys Val Thr Asn Asp Trp Thr Arg Cys Arg 115 120 125 Lys Glu Leu Glu His Arg Glu Ala Ala Trp Arg Arg Glu Glu Glu Ser 130 135 140 Phe Asn Ala Tyr Phe Ser Asn Glu His Ser Arg Leu Leu Leu Leu Trp 145 150 155 160 Arg Gln Val Val Gly Phe Arg Arg Leu Val Ser Glu Val Lys Met Phe 165 170 175 Thr Glu Arg Asp Leu Leu Gln Leu Gly Gly Glu Leu Ala Arg Thr Ser 180 185 190 Arg Ala Val Gln Glu Ala Gly Leu Gly Leu Ser Thr Gly Leu Arg Leu 195 200 205 Ala Glu Ser Arg Ala Glu Ala Ala Leu Glu Lys Gln Ala Leu Leu Gln 210 215 220 Ala Gln Leu Glu Glu Gln Leu Arg Asp Lys Val Leu Arg Glu Lys Asp 225 230 235 240 Leu Ala Gln Gln Gln Met Gln Ser Asp Leu Asp Lys Ala Asp Leu Ser 245 250 255 Ala Arg Val Thr Glu Leu Gly Leu Ala Val Lys Arg Leu Glu Lys Gln 260 265 270 Asn Leu Glu Lys Asp Gln Val Asn Lys Asp Leu Thr Glu Lys Leu Glu 275 280 285 Ala Leu Glu Ser Leu Arg Leu Gln Glu Gln Ala Ala Leu Glu Thr Glu 290 295 300 Asp Gly Glu Gly Leu Gln Gln Thr Leu Arg Asp Leu Ala Gln Ala Val 305 310 315 320 Leu Ser Asp Ser Glu Ser Gly Val Gln Leu Ser Gly Ser Glu Arg Thr 325 330 335 Ala Asp Ala Ser Asn Gly Ser Leu Arg Gly Leu Ser Gly Gln Arg Thr 340 345 350 Pro Ser Pro Pro Arg Arg Ser Ser Pro Gly Arg Gly Arg Ser Pro Arg 355 360 365 Arg Gly Pro Ser Pro Ala Cys Ser Asp Ser Ser Thr Leu Ala Leu Ile 370 375 380 His Ser Ala Leu His Lys Arg Gln Leu Gln Val Gln Asp Met Arg Gly 385 390 395 400 Arg Tyr Glu Ala Ser Gln Asp Leu Leu Gly Thr Leu Arg Lys Gln Leu 405 410 415 Ser Asp Ser Glu Ser Glu Arg Arg Ala Leu Glu Glu Gln Leu Gln Arg 420 425 430 Leu Arg Asp Lys Thr Asp Gly Ala Met Gln Ala His Glu Asp Ala Gln 435 440 445 Arg Glu Val Gln Arg Leu Arg Ser Ala Asn Glu Leu Leu Ser Arg Glu 450 455 460 Lys Ser Asn Leu Ala His Ser Leu Gln Val Ala Gln Gln Gln Ala Glu 465 470 475 480 Glu Leu Arg Gln Glu Arg Glu Lys Leu Gln Ala Ala Gln Glu Glu Leu 485 490 495 Arg Arg Gln Arg Asp Arg Leu Glu Glu Glu Gln Glu Asp Ala Val Gln 500 505 510 Asp Gly Ala Arg Val Arg Arg Glu Leu Glu Arg Ser His Arg Gln Leu 515 520 525 Glu Gln Leu Glu Gly Lys Arg Ser Val Leu Ala Lys Glu Leu Val Glu 530 535 540 Val Arg Glu Ala Leu Ser Arg Ala Thr Leu Gln Arg Asp Met Leu Gln 545 550 555 560 Ala Glu Lys Ala Glu Val Ala Glu Ala Leu Thr Lys Ala Glu Ala Gly 565 570 575 Arg Val Glu Leu Glu Leu Ser Met Thr Lys Leu Arg Ala Glu Glu Ala 580 585 590 Ser Leu Gln Asp Ser Leu Ser Lys Leu Ser Ala Leu Asn Glu Ser Leu 595 600 605 Ala Gln Asp Lys Leu Asp Leu Asn Arg Leu Val Ala Gln Leu Glu Glu 610 615 620 Glu Lys Ser Ala Leu Gln Gly Arg Gln Arg Gln Ala Glu Gln Glu Ala 625 630 635 640 Thr Val Ala Arg Glu Glu Gln Glu Arg Leu Glu Glu Leu Arg Leu Glu 645 650 655 Gln Glu Val Ala Arg Gln Gly Leu Glu Gly Ser Leu Arg Val Ala Glu 660 665 670 Gln Ala Gln Glu Ala Leu Glu Gln Gln Leu Pro Thr Leu Arg His Glu 675 680 685 Arg Ser Gln Leu Gln Glu Gln Leu Ala Gln Leu Ser Arg Gln Leu Ser 690 695 700 Gly Arg Glu Gln Glu Leu Glu Gln Ala Arg Arg Glu Ala Gln Arg Gln 705 710 715 720 Val Glu Ala Leu Glu Arg Ala Ala Arg Glu Lys Glu Ala Leu Ala Lys 725 730 735 Glu His Ala Gly Leu Ala Val Gln Leu Val Ala Ala Glu Arg Glu Gly 740 745 750 Arg Thr Leu Ser Glu Glu Ala Thr Arg Leu Arg Leu Glu Lys Glu Ala 755 760 765 Leu Glu Gly Ser Leu Phe Glu Val Gln Arg Gln Leu Ala Gln Leu Glu 770 775 780 Ala Arg Arg Glu Gln Leu Glu Ala Glu Gly Gln Ala Leu Leu Leu Ala 785 790 795 800 Lys Glu Thr Leu Thr Gly Glu Leu Ala Gly Leu Arg Gln Gln Ile Ile 805 810 815 Ala Thr Gln Glu Lys Ala Ser Leu Asp Lys Glu Leu Met Ala Gln Lys 820 825 830 Leu Val Gln Ala Glu Arg Glu Ala Gln Ala Ser Leu Arg Glu Gln Arg 835 840 845 Ala Ala His Glu Glu Asp Leu Gln Arg Leu Gln Arg Glu Lys Glu Ala 850 855 860 Ala Trp Arg Glu Leu Glu Ala Glu Arg Ala Gln Leu Gln Ser Gln Leu 865 870 875 880 Gln Arg Glu Gln Glu Glu Leu Leu Ala Arg Leu Glu Ala Glu Lys Glu 885 890 895 Glu Leu Ser Glu Glu Ile Ala Ala Leu Gln Gln Glu Arg Asp Glu Gly 900 905 910 Leu Leu Leu Ala Glu Ser Glu Lys Gln Gln Ala Leu Ser Leu Lys Glu 915 920 925 Ser Glu Lys Thr Ala Leu Ser Glu Lys Leu Met Gly Thr Arg His Ser 930 935 940 Leu Ala Thr Ile Ser Leu Glu Met Glu Arg Gln Lys Arg Asp Ala Gln 945 950 955 960 Ser Arg Gln Glu Gln Asp Arg Ser Thr Val Asn Ala Leu Thr Ser Glu 965 970 975 Leu Arg Asp Leu Arg Ala Gln Arg Glu Glu Ala Ala Ala Ala His Ala 980 985 990 Gln Glu Val Arg Arg Leu Gln Glu Gln Ala Arg Asp Leu Gly Lys Gln 995 1000 1005 Arg Asp Ser Cys Leu Arg Glu Ala Glu Glu Leu Arg Thr Gln Leu 1010 1015 1020 Arg Leu Leu Glu Asp Ala Arg Asp Gly Leu Arg Arg Glu Leu Leu 1025 1030 1035 Glu Ala Gln Arg Lys Leu Arg Glu Ser Gln Glu Gly Arg Glu Val 1040 1045 1050 Gln Arg Gln Glu Ala Gly Glu Leu Arg Arg Ser Leu Gly Glu Gly 1055 1060 1065 Ala Lys Glu Arg Glu Ala Leu Arg Arg Ser Asn Glu Glu Leu Arg 1070 1075 1080 Ser Ala Val Lys Lys Ala Glu Ser Glu Arg Ile Ser Leu Lys Leu 1085 1090 1095 Ala Asn Glu Asp Lys Glu Gln Lys Leu Ala Leu Leu Glu Glu Ala 1100 1105 1110 Arg Thr Ala Val Gly Lys Glu Ala Gly Glu Leu Arg Thr Gly Leu 1115 1120 1125 Gln Glu Val Glu Arg Ser Arg Leu Glu Ala Arg Arg Glu Leu Gln 1130 1135 1140 Glu Leu Arg Arg Gln Met Lys Met Leu Asp Ser Glu Asn Thr Arg 1145 1150 1155 Leu Gly Arg Glu Leu Ala Glu Leu Gln Gly Arg Leu Ala Leu Gly 1160 1165 1170 Glu Arg Ala Glu Lys Glu Ser Arg Arg Glu Thr Leu Gly Leu Arg 1175 1180 1185 Gln Arg Leu Leu Lys Gly Glu Ala Ser Leu Glu Val Met Arg Gln 1190 1195 1200 Glu Leu Gln Val Ala Gln Arg Lys Leu Gln Glu Gln Glu Gly Glu 1205 1210 1215 Phe Arg Thr Arg Glu Arg Arg Leu Leu Gly Ser Leu Glu Glu Ala 1220 1225 1230 Arg Gly Thr Glu Lys Gln Gln Leu Asp His Ala Arg Gly Leu Glu 1235 1240 1245 Leu Lys Leu Glu Ala Ala Arg Ala Glu Ala Ala Glu Leu Gly Leu 1250 1255 1260 Arg Leu Ser Ala Ala Glu Gly Arg Ala Gln Gly Leu Glu Ala Glu 1265 1270 1275 Leu Ala Arg Val Glu Val Gln Arg Arg Ala Ala Glu Ala Gln Leu 1280 1285 1290 Gly Gly Leu Arg Ser Ala Leu Arg Arg Gly Leu Gly Leu Gly Arg 1295 1300 1305 Ala Pro Ser 1310 <210> 40 <211> 154 <212> PRT <213> Homo sapiens <400> 40 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 Glu Ser Asn Gly Pro Val Lys Val 20 25 30 Trp Gly Ser Ile Lys Gly Leu Thr Glu Gly Leu His Gly Phe His Val 35 40 45 His Glu Phe Gly Asp Asn Thr Ala Gly Cys Thr Ser Ala Gly Pro His 50 55 60 Phe Asn Pro Leu Ser Arg Lys His Gly Gly Pro Lys Asp Glu Glu Arg 65 70 75 80 His Val Gly Asp Leu Gly Asn Val Thr Ala Asp Lys Asp Gly Val Ala 85 90 95 Asp Val Ser Ile Glu Asp Ser Val Ile Ser Leu Ser Gly Asp His Cys 100 105 110 Ile Ile Gly Arg Thr Leu Val Val His Glu Lys Ala Asp Asp Leu Gly 115 120 125 Lys Gly Gly Asn Glu Glu Ser Thr Lys Thr Gly Asn Ala Gly Ser Arg 130 135 140 Leu Ala Cys Gly Val Ile Gly Ile Ala Gln 145 150 <210> 41 <211> 324 <212> PRT <213> Homo sapiens <400> 41 Met Asp Ser Lys Tyr Gln Cys Val Lys Leu Asn Asp Gly His Phe Met 1 5 10 15 Pro Val Leu Gly Phe Gly Thr Tyr Ala Pro Ala Glu Val Pro Lys Ser 20 25 30 Lys Ala Leu Glu Ala Thr Lys Leu Ala Ile Glu Ala Gly Phe Arg His 35 40 45 Ile Asp Ser Ala His Leu Tyr Asn Asn Glu Glu Gln Val Gly Leu Ala 50 55 60 Ile Arg Ser Lys Ile Ala Asp Gly Ser Val Lys Arg Glu Asp Ile Phe 65 70 75 80 Tyr Thr Ser Lys Leu Trp Cys Asn Ser His Arg Pro Glu Leu Val Arg 85 90 95 Pro Ala Leu Glu Arg Ser Leu Lys Asn Leu Gln Leu Asp Tyr Val Asp 100 105 110 Leu Tyr Leu Ile His Phe Pro Val Ser Val Lys Pro Gly Glu Glu Val 115 120 125 Ile Pro Lys Asp Glu Asn Gly Lys Ile Leu Phe Asp Thr Val Asp Leu 130 135 140 Cys Ala Thr Trp Glu Val Met Glu Lys Cys Lys Asp Ala Gly Leu Ala 145 150 155 160 Lys Ser Ile Gly Val Ser Asn Phe Asn Arg Arg Gln Leu Glu Met Ile 165 170 175 Leu Asn Lys Pro Gly Leu Lys Tyr Lys Pro Val Cys Asn Gln Val Glu 180 185 190 Cys His Pro Tyr Phe Asn Gln Arg Lys Leu Leu Asp Phe Cys Lys Ser 195 200 205 Lys Asp Ile Val Leu Val Ala Tyr Ser Ala Leu Gly Ser His Arg Glu 210 215 220 Glu Pro Trp Val Asp Pro Asn Ser Pro Val Leu Leu Glu Asp Pro Val 225 230 235 240 Leu Cys Ala Leu Ala Lys Lys His Lys Arg Thr Pro Ala Leu Ile Ala 245 250 255 Leu Arg Tyr Gln Leu Gln Arg Gly Val Val Val Leu Ala Lys Ser Tyr 260 265 270 Asn Glu Gln Arg Ile Arg Gln Asn Val Gln Val Phe Glu Phe Gln Leu 275 280 285 Thr Ser Glu Glu Met Lys Ala Ile Asp Gly Leu Asn Arg Asn Val Arg 290 295 300 Tyr Leu Thr Leu Asp Met Tyr Phe Ala Ser His Pro Asn Tyr Pro Tyr 305 310 315 320 Ser Asp Glu Tyr <210> 42 <211> 114 <212> PRT <213> Homo sapiens <400> 42 Met Ala Ser Val Ser Glu Leu Ala Cys Ile Tyr Ser Ala Leu Ile Leu 1 5 10 15 His Asp Asp Glu Val Thr Val Thr Glu Asp Lys Ile Asn Ala Leu Ile 20 25 30 Lys Ala Ala Gly Val Asn Val Glu Pro Phe Trp Pro Gly Leu Phe Ala 35 40 45 Lys Ala Leu Ala Asn Val Asn Ile Gly Ser Leu Ile Cys Asn Val Gly 50 55 60 Ala Gly Gly Pro Ala Pro Ala Ala Gly Ala Ala Pro Ala Gly Gly Pro 65 70 75 80 Ala Pro Ser Thr Ala Ala Ala Pro Ala Glu Glu Lys Lys Val Glu Ala 85 90 95 Lys Lys Glu Glu Ser Glu Glu Ser Asp Asp Asp Met Gly Phe Gly Leu 100 105 110 Phe Asp <210> 43 <211> 945 <212> PRT <213> Homo sapiens <400> 43 Met Lys Arg Leu Thr Cys Phe Phe Ile Cys Phe Phe Leu Ser Glu Val 1 5 10 15 Ser Gly Phe Glu Ile Pro Ile Asn Gly Leu Ser Glu Phe Val Asp Tyr 20 25 30 Glu Asp Leu Val Glu Leu Ala Pro Gly Lys Phe Gln Leu Val Ala Glu 35 40 45 Asn Arg Arg Tyr Gln Arg Ser Leu Pro Gly Glu Ser Glu Glu Met Met 50 55 60 Glu Glu Val Asp Gln Val Thr Leu Tyr Ser Tyr Lys Val Gln Ser Thr 65 70 75 80 Ile Thr Ser Arg Met Ala Thr Thr Met Ile Gln Ser Lys Val Val Asn 85 90 95 Asn Ser Pro Gln Pro Gln Asn Val Val Phe Asp Val Gln Ile Pro Lys 100 105 110 Gly Ala Phe Ile Ser Asn Phe Ser Met Thr Val Asp Gly Lys Thr Phe 115 120 125 Arg Ser Ser Ile Lys Glu Lys Thr Val Gly Arg Ala Leu Tyr Ala Gln 130 135 140 Ala Arg Ala Lys Gly Lys Thr Ala Gly Leu Val Arg Ser Ser Ala Leu 145 150 155 160 Asp Met Glu Asn Phe Arg Thr Glu Val Asn Val Leu Pro Gly Ala Lys 165 170 175 Val Gln Phe Glu Leu His Tyr Gln Glu Val Lys Trp Arg Lys Leu Gly 180 185 190 Ser Tyr Glu His Arg Ile Tyr Leu Gln Pro Gly Arg Leu Ala Lys His 195 200 205 Leu Glu Val Asp Val Trp Val Ile Glu Pro Gln Gly Leu Arg Phe Leu 210 215 220 His Val Pro Asp Thr Phe Glu Gly His Phe Asp Gly Val Pro Val Ile 225 230 235 240 Ser Lys Gly Gln Gln Lys Ala His Val Ser Phe Lys Pro Thr Val Ala 245 250 255 Gln Gln Arg Ile Cys Pro Asn Cys Arg Glu Thr Ala Val Asp Gly Glu 260 265 270 Leu Val Val Leu Tyr Asp Val Lys Arg Glu Glu Lys Ala Gly Glu Leu 275 280 285 Glu Val Phe Asn Gly Tyr Phe Val His Phe Phe Ala Pro Asp Asn Leu 290 295 300 Asp Pro Ile Pro Lys Asn Ile Leu Phe Val Ile Asp Val Ser Gly Ser 305 310 315 320 Met Trp Gly Val Lys Met Lys Gln Thr Val Glu Ala Met Lys Thr Ile 325 330 335 Leu Asp Asp Leu Arg Ala Glu Asp His Phe Ser Val Ile Asp Phe Asn 340 345 350 Gln Asn Ile Arg Thr Trp Arg Asn Asp Leu Phe Gln Leu Gln Lys His 355 360 365 Arg Leu Gln Met Pro Arg Tyr Ile Glu Lys Ile Gln Pro Ser Gly Gly 370 375 380 Thr Asn Ile Asn Glu Ala Leu Leu Arg Ala Ile Phe Ile Leu Asn Glu 385 390 395 400 Ala Asn Asn Leu Gly Leu Leu Asp Pro Asn Ser Val Ser Leu Ile Ile 405 410 415 Leu Val Ser Asp Gly Asp Pro Thr Val Gly Glu Leu Lys Leu Ser Lys 420 425 430 Ile Gln Lys Asn Val Lys Glu Asn Ile Gln Asp Asn Ile Ser Leu Phe 435 440 445 Ser Leu Gly Met Gly Phe Asp Val Asp Tyr Asp Phe Leu Lys Arg Leu 450 455 460 Ser Asn Glu Asn His Gly Ile Ala Gln Arg Ile Tyr Gly Asn Gln Asp 465 470 475 480 Thr Ser Ser Gln Leu Lys Lys Phe Tyr Asn Gln Val Ser Thr Pro Leu 485 490 495 Leu Arg Asn Val Gln Phe Asn Tyr Pro His Thr Ser Val Thr Asp Val 500 505 510 Thr Gln Asn Asn Phe His Asn Tyr Phe Gly Gly Ser Glu Ile Val Val 515 520 525 Ala Gly Lys Phe Asp Pro Ala Lys Leu Asp Gln Ile Glu Ser Val Ile 530 535 540 Thr Ala Thr Ser Ala Asn Thr Gln Leu Val Leu Glu Thr Leu Ala Gln 545 550 555 560 Met Asp Asp Leu Gln Asp Phe Leu Ser Lys Asp Lys His Ala Asp Pro 565 570 575 Asp Phe Thr Arg Lys Leu Trp Ala Tyr Leu Thr Ile Asn Gln Leu Leu 580 585 590 Ala Glu Arg Ser Leu Ala Pro Thr Ala Ala Ala Lys Arg Arg Ile Thr 595 600 605 Arg Ser Ile Leu Gln Met Ser Leu Asp His His Ile Val Thr Pro Leu 610 615 620 Thr Ser Leu Val Ile Glu Asn Glu Ala Gly Asp Glu Arg Met Leu Ala 625 630 635 640 Asp Ala Pro Pro Gln Asp Pro Ser Cys Cys Ser Gly Ala Leu Tyr Tyr 645 650 655 Gly Ser Lys Val Val Pro Asp Ser Thr Pro Ser Trp Ala Asn Pro Ser 660 665 670 Pro Thr Pro Val Ile Ser Met Leu Ala Gln Gly Ser Gln Val Leu Glu 675 680 685 Ser Thr Pro Pro Pro His Val Met Arg Val Glu Asn Asp Pro His Phe 690 695 700 Ile Ile Tyr Leu Pro Lys Ser Gln Lys Asn Ile Cys Phe Asn Ile Asp 705 710 715 720 Ser Glu Pro Gly Lys Ile Leu Asn Leu Val Ser Asp Pro Glu Ser Gly 725 730 735 Ile Val Val Asn Gly Gln Leu Val Gly Ala Lys Lys Pro Asn Asn Gly 740 745 750 Lys Leu Ser Thr Tyr Phe Gly Lys Leu Gly Phe Tyr Phe Gln Ser Glu 755 760 765 Asp Ile Lys Ile Glu Ile Ser Thr Glu Thr Ile Thr Leu Ser His Gly 770 775 780 Ser Ser Thr Phe Ser Leu Ser Trp Ser Asp Thr Ala Gln Val Thr Asn 785 790 795 800 Gln Arg Val Gln Ile Ser Val Lys Lys Glu Lys Val Val Thr Ile Thr 805 810 815 Leu Asp Lys Glu Met Ser Phe Ser Val Leu Leu His Arg Val Trp Lys 820 825 830 Lys His Pro Val Asn Val Asp Phe Leu Gly Ile Tyr Ile Pro Pro Thr 835 840 845 Asn Lys Phe Ser Pro Lys Ala His Gly Leu Ile Gly Gln Phe Met Gln 850 855 860 Glu Pro Lys Ile His Ile Phe Asn Glu Arg Pro Gly Lys Asp Pro Glu 865 870 875 880 Lys Pro Glu Ala Ser Met Glu Val Lys Gly Gln Lys Leu Ile Ile Thr 885 890 895 Arg Gly Leu Gln Lys Asp Tyr Arg Thr Asp Leu Val Phe Gly Thr Asp 900 905 910 Val Thr Cys Trp Phe Val His Asn Ser Gly Lys Gly Phe Ile Asp Gly 915 920 925 His Tyr Lys Asp Tyr Phe Val Pro Gln Leu Tyr Ser Phe Leu Lys Arg 930 935 940 Pro 945 <210> 44 <211> 90 <212> PRT <213> Homo sapiens <400> 44 Met Lys Phe Leu Ala Val Leu Val Leu Leu Gly Val Ser Ile Phe Leu 1 5 10 15 Val Ser Ala Gln Asn Pro Thr Thr Ala Ala Pro Ala Asp Thr Tyr Pro 20 25 30 Ala Thr Gly Pro Ala Asp Asp Glu Ala Pro Asp Ala Glu Thr Thr Ala 35 40 45 Ala Ala Thr Thr Ala Thr Thr Ala Ala Pro Thr Thr Ala Thr Thr Ala 50 55 60 Ala Ser Thr Thr Ala Arg Lys Asp Ile Pro Val Leu Pro Lys Trp Val 65 70 75 80 Gly Asp Leu Pro Asn Gly Arg Val Cys Pro 85 90 <210> 45 <211> 90 <212> PRT <213> Homo sapiens <400> 45 Met Ala Cys Pro Leu Asp Gln Ala Ile Gly Leu Leu Val Ala Ile Phe 1 5 10 15 His Lys Tyr Ser Gly Arg Glu Gly Asp Lys His Thr Leu Ser Lys Lys 20 25 30 Glu Leu Lys Glu Leu Ile Gln Lys Glu Leu Thr Ile Gly Ser Lys Leu 35 40 45 Gln Asp Ala Glu Ile Ala Arg Leu Met Glu Asp Leu Asp Arg Asn Lys 50 55 60 Asp Gln Glu Val Asn Phe Gln Glu Tyr Val Thr Phe Leu Gly Ala Leu 65 70 75 80 Ala Leu Ile Tyr Asn Glu Ala Leu Lys Gly 85 90 <210> 46 <211> 358 <212> PRT <213> Homo sapiens <400> 46 Met Ser Ala Asp Ala Ala Ala Gly Ala Pro Leu Pro Arg Leu Cys Cys 1 5 10 15 Leu Glu Lys Gly Pro Asn Gly Tyr Gly Phe His Leu His Gly Glu Lys 20 25 30 Gly Lys Leu Gly Gln Tyr Ile Arg Leu Val Glu Pro Gly Ser Pro Ala 35 40 45 Glu Lys Ala Gly Leu Leu Ala Gly Asp Arg Leu Val Glu Val Asn Gly 50 55 60 Glu Asn Val Glu Lys Glu Thr His Gln Gln Val Val Ser Arg Ile Arg 65 70 75 80 Ala Ala Leu Asn Ala Val Arg Leu Leu Val Val Asp Pro Glu Thr Asp 85 90 95 Glu Gln Leu Gln Lys Leu Gly Val Gln Val Arg Glu Glu Leu Leu Arg 100 105 110 Ala Gln Glu Ala Pro Gly Gln Ala Glu Pro Pro Ala Ala Ala Glu Val 115 120 125 Gln Gly Ala Gly Asn Glu Asn Glu Pro Arg Glu Ala Asp Lys Ser His 130 135 140 Pro Glu Gln Arg Glu Leu Arg Pro Arg Leu Cys Thr Met Lys Lys Gly 145 150 155 160 Pro Ser Gly Tyr Gly Phe Asn Leu His Ser Asp Lys Ser Lys Pro Gly 165 170 175 Gln Phe Ile Arg Ser Val Asp Pro Asp Ser Pro Ala Glu Ala Ser Gly 180 185 190 Leu Arg Ala Gln Asp Arg Ile Val Glu Val Asn Gly Val Cys Met Glu 195 200 205 Gly Lys Gln His Gly Asp Val Val Ser Ala Ile Arg Ala Gly Gly Asp 210 215 220 Glu Thr Lys Leu Leu Val Val Asp Arg Glu Thr Asp Glu Phe Phe Lys 225 230 235 240 Lys Cys Arg Val Ile Pro Ser Gln Glu His Leu Asn Gly Pro Leu Pro 245 250 255 Val Pro Phe Thr Asn Gly Glu Ile Gln Lys Glu Asn Ser Arg Glu Ala 260 265 270 Leu Ala Glu Ala Ala Leu Glu Ser Pro Arg Pro Ala Leu Val Arg Ser 275 280 285 Ala Ser Ser Asp Thr Ser Glu Glu Leu Asn Ser Gln Asp Ser Pro Pro 290 295 300 Lys Gln Asp Ser Thr Ala Pro Ser Ser Thr Ser Ser Ser Asp Pro Ile 305 310 315 320 Leu Asp Phe Asn Ile Ser Leu Ala Met Ala Lys Glu Arg Ala His Gln 325 330 335 Lys Arg Ser Ser Lys Arg Ala Pro Gln Met Asp Trp Ser Lys Lys Asn 340 345 350 Glu Leu Phe Ser Asn Leu 355 <210> 47 <211> 75 <212> PRT <213> Homo sapiens <400> 47 Met Ala Arg Tyr Glu Glu Val Ser Val Ser Gly Phe Glu Glu Phe His 1 5 10 15 Arg Ala Val Glu Gln His Asn Gly Lys Thr Ile Phe Ala Tyr Phe Thr 20 25 30 Gly Ser Lys Asp Ala Gly Gly Lys Ser Trp Cys Pro Asp Cys Val Gln 35 40 45 Ala Glu Pro Val Val Arg Glu Gly Leu Lys His Ile Ser Glu Gly Cys 50 55 60 Val Phe Ile Tyr Cys Gln Val Gly Glu Lys Pro 65 70 75 <210> 48 <211> 339 <212> PRT <213> Homo sapiens <400> 48 Met Ala Glu Ala Ser Ser Asp Pro Gly Ala Glu Glu Arg Glu Glu Leu 1 5 10 15 Leu Gly Pro Thr Ala Gln Trp Ser Val Glu Asp Glu Glu Glu Ala Val 20 25 30 His Glu Gln Cys Gln His Glu Arg Asp Arg Gln Leu Gln Ala Gln Asp 35 40 45 Glu Glu Gly Gly Gly His Val Pro Glu Arg Pro Lys Gln Glu Met Leu 50 55 60 Leu Ser Leu Lys Pro Ser Glu Ala Pro Glu Leu Asp Glu Asp Glu Gly 65 70 75 80 Phe Gly Asp Trp Ser Gln Arg Pro Glu Gln Arg Gln Gln His Glu Gly 85 90 95 Ala Gln Gly Ala Leu Asp Ser Gly Glu Pro Pro Gln Cys Arg Ser Pro 100 105 110 Glu Gly Glu Gln Glu Asp Arg Pro Gly Leu His Ala Tyr Glu Lys Glu 115 120 125 Asp Ser Asp Glu Val His Leu Glu Glu Leu Ser Leu Ser Lys Glu Gly 130 135 140 Pro Gly Pro Glu Asp Thr Val Gln Asp Asn Leu Gly Ala Ala Gly Ala 145 150 155 160 Glu Glu Glu Gln Glu Glu His Gln Lys Cys Gln Gln Pro Arg Thr Pro 165 170 175 Ser Pro Leu Val Leu Glu Gly Thr Ile Glu Gln Ser Ser Pro Pro Leu 180 185 190 Ser Pro Thr Thr Lys Leu Ile Asp Arg Thr Glu Ser Leu Asn Arg Ser 195 200 205 Ile Glu Lys Ser Asn Ser Val Lys Lys Ser Gln Pro Asp Leu Pro Ile 210 215 220 Ser Lys Ile Asp Gln Trp Leu Glu Gln Tyr Thr Gln Ala Ile Glu Thr 225 230 235 240 Ala Gly Arg Thr Pro Lys Leu Ala Arg Gln Ala Ser Ile Glu Leu Pro 245 250 255 Ser Met Ala Val Ala Ser Thr Lys Ser Arg Trp Glu Thr Gly Glu Val 260 265 270 Gln Ala Gln Ser Ala Ala Lys Thr Pro Ser Cys Lys Asp Ile Val Ala 275 280 285 Gly Asp Met Ser Lys Lys Ser Leu Trp Glu Gln Lys Gly Gly Ser Lys 290 295 300 Thr Ser Ser Thr Ile Lys Ser Thr Pro Ser Gly Lys Arg Tyr Lys Phe 305 310 315 320 Val Ala Thr Gly His Gly Lys Tyr Glu Lys Val Leu Val Glu Gly Gly 325 330 335 Pro Ala Pro <210> 49 <211> 177 <212> PRT <213> Homo sapiens <400> 49 Met Asp Leu Thr Thr Thr Met Ser Ser Lys Arg Thr Lys Thr Lys Thr 1 5 10 15 Lys Lys Arg Pro Gln Arg Ala Thr Ser Asn Val Phe Ala Met Phe Asp 20 25 30 Gln Ser Gln Ile Gln Glu Phe Lys Glu Ala Phe Asn Met Ile Asp Gln 35 40 45 Asn Arg Asp Gly Phe Ile Asp Lys Glu Asp Leu His Asp Met Leu Ala 50 55 60 Ser Leu Gly Lys Asn Pro Thr Asp Glu Tyr Leu Asp Ala Met Met Asn 65 70 75 80 Glu Ala Pro Gly Pro Ile Asn Phe Thr Met Phe Leu Thr Met Phe Gly 85 90 95 Glu Lys Leu Asn Gly Thr Asp Pro Glu Asp Val Ile Arg Asn Ala Phe 100 105 110 Ala Cys Phe Asp Glu Glu Ala Thr Gly Thr Ile Gln Glu Asp Tyr Leu 115 120 125 Arg Glu Leu Leu Thr Thr Met Gly Asp Arg Phe Thr Asp Glu Glu Val 130 135 140 Asp Glu Leu Tyr Arg Glu Ala Pro Ile Asp Lys Lys Gly Asn Phe Asn 145 150 155 160 Tyr Ile Glu Phe Thr Arg Ile Leu Lys His Gly Ala Lys Asp Lys Asp 165 170 175 Asp <210> 50 <211> 461 <212> PRT <213> Homo sapiens <400> 50 Met Ser Leu Asp Ile Gln Ser Leu Asp Ile Gln Cys Glu Glu Leu Ser 1 5 10 15 Asp Ala Arg Trp Ala Glu Leu Leu Pro Leu Leu Gln Gln Cys Gln Val 20 25 30 Val Arg Leu Asp Asp Cys Gly Leu Thr Glu Ala Arg Cys Lys Asp Ile 35 40 45 Ser Ser Ala Leu Arg Val Asn Pro Ala Leu Ala Glu Leu Asn Leu Arg 50 55 60 Ser Asn Glu Leu Gly Asp Val Gly Val His Cys Val Leu Gln Gly Leu 65 70 75 80 Gln Thr Pro Ser Cys Lys Ile Gln Lys Leu Ser Leu Gln Asn Cys Cys 85 90 95 Leu Thr Gly Ala Gly Cys Gly Val Leu Ser Ser Thr Leu Arg Thr Leu 100 105 110 Pro Thr Leu Gln Glu Leu His Leu Ser Asp Asn Leu Leu Gly Asp Ala 115 120 125 Gly Leu Gln Leu Leu Cys Glu Gly Leu Leu Asp Pro Gln Cys Arg Leu 130 135 140 Glu Lys Leu Gln Leu Glu Tyr Cys Ser Leu Ser Ala Ala Ser Cys Glu 145 150 155 160 Pro Leu Ala Ser Val Leu Arg Ala Lys Pro Asp Phe Lys Glu Leu Thr 165 170 175 Val Ser Asn Asn Asp Ile Asn Glu Ala Gly Val Arg Val Leu Cys Gln 180 185 190 Gly Leu Lys Asp Ser Pro Cys Gln Leu Glu Ala Leu Lys Leu Glu Ser 195 200 205 Cys Gly Val Thr Ser Asp Asn Cys Arg Asp Leu Cys Gly Ile Val Ala 210 215 220 Ser Lys Ala Ser Leu Arg Glu Leu Ala Leu Gly Ser Asn Lys Leu Gly 225 230 235 240 Asp Val Gly Met Ala Glu Leu Cys Pro Gly Leu Leu His Pro Ser Ser 245 250 255 Arg Leu Arg Thr Leu Trp Ile Trp Glu Cys Gly Ile Thr Ala Lys Gly 260 265 270 Cys Gly Asp Leu Cys Arg Val Leu Arg Ala Lys Glu Ser Leu Lys Glu 275 280 285 Leu Ser Leu Ala Gly Asn Glu Leu Gly Asp Glu Gly Ala Arg Leu Leu 290 295 300 Cys Glu Thr Leu Leu Glu Pro Gly Cys Gln Leu Glu Ser Leu Trp Val 305 310 315 320 Lys Ser Cys Ser Phe Thr Ala Ala Cys Cys Ser His Phe Ser Ser Val 325 330 335 Leu Ala Gln Asn Arg Phe Leu Leu Glu Leu Gln Ile Ser Asn Asn Arg 340 345 350 Leu Glu Asp Ala Gly Val Arg Glu Leu Cys Gln Gly Leu Gly Gln Pro 355 360 365 Gly Ser Val Leu Arg Val Leu Trp Leu Ala Asp Cys Asp Val Ser Asp 370 375 380 Ser Ser Cys Ser Ser Leu Ala Ala Thr Leu Leu Ala Asn His Ser Leu 385 390 395 400 Arg Glu Leu Asp Leu Ser Asn Asn Cys Leu Gly Asp Ala Gly Ile Leu 405 410 415 Gln Leu Val Glu Ser Val Arg Gln Pro Gly Cys Leu Leu Glu Gln Leu 420 425 430 Val Leu Tyr Asp Ile Tyr Trp Ser Glu Glu Met Glu Asp Arg Leu Gln 435 440 445 Ala Leu Glu Lys Asp Lys Pro Ser Leu Arg Val Ile Ser 450 455 460 <210> 51 <211> 434 <212> PRT <213> Homo sapiens <400> 51 Met Ser Ile Leu Lys Ile His Ala Arg Glu Ile Phe Asp Ser Arg Gly 1 5 10 15 Asn Pro Thr Val Glu Val Asp Leu Phe Thr Ser Lys Gly Leu Phe Arg 20 25 30 Ala Ala Val Pro Ser Gly Ala Ser Thr Gly Ile Tyr Glu Ala Leu Glu 35 40 45 Leu Arg Asp Asn Asp Lys Thr Arg Tyr Met Gly Lys Gly Val Ser Lys 50 55 60 Ala Val Glu His Ile Asn Lys Thr Ile Ala Pro Ala Leu Val Ser Lys 65 70 75 80 Lys Leu Asn Val Thr Glu Gln Glu Lys Ile Asp Lys Leu Met Ile Glu 85 90 95 Met Asp Gly Thr Glu Asn Lys Ser Lys Phe Gly Ala Asn Ala Ile Leu 100 105 110 Gly Val Ser Leu Ala Val Cys Lys Ala Gly Ala Val Glu Lys Gly Val 115 120 125 Pro Leu Tyr Arg His Ile Ala Asp Leu Ala Gly Asn Ser Glu Val Ile 130 135 140 Leu Pro Val Pro Ala Phe Asn Val Ile Asn Gly Gly Ser His Ala Gly 145 150 155 160 Asn Lys Leu Ala Met Gln Glu Phe Met Ile Leu Pro Val Gly Ala Ala 165 170 175 Asn Phe Arg Glu Ala Met Arg Ile Gly Ala Glu Val Tyr His Asn Leu 180 185 190 Lys Asn Val Ile Lys Glu Lys Tyr Gly Lys Asp Ala Thr Asn Val Gly 195 200 205 Asp Glu Gly Gly Phe Ala Pro Asn Ile Leu Glu Asn Lys Glu Gly Leu 210 215 220 Glu Leu Leu Lys Thr Ala Ile Gly Lys Ala Gly Tyr Thr Asp Lys Val 225 230 235 240 Val Ile Gly Met Asp Val Ala Ala Ser Glu Phe Phe Arg Ser Gly Lys 245 250 255 Tyr Asp Leu Asp Phe Lys Ser Pro Asp Asp Pro Ser Arg Tyr Ile Ser 260 265 270 Pro Asp Gln Leu Ala Asp Leu Tyr Lys Ser Phe Ile Lys Asp Tyr Pro 275 280 285 Val Val Ser Ile Glu Asp Pro Phe Asp Gln Asp Asp Trp Gly Ala Trp 290 295 300 Gln Lys Phe Thr Ala Ser Ala Gly Ile Gln Val Val Gly Asp Asp Leu 305 310 315 320 Thr Val Thr Asn Pro Lys Arg Ile Ala Lys Ala Val Asn Glu Lys Ser 325 330 335 Cys Asn Cys Leu Leu Leu Lys Val Asn Gln Ile Gly Ser Val Thr Glu 340 345 350 Ser Leu Gln Ala Cys Lys Leu Ala Gln Ala Asn Gly Trp Gly Val Met 355 360 365 Val Ser His Arg Ser Gly Glu Thr Glu Asp Thr Phe Ile Ala Asp Leu 370 375 380 Val Val Gly Leu Cys Thr Gly Gln Ile Lys Thr Gly Ala Pro Cys Arg 385 390 395 400 Ser Glu Arg Leu Ala Lys Tyr Asn Gln Leu Leu Arg Ile Glu Glu Glu 405 410 415 Leu Gly Ser Lys Ala Lys Phe Ala Gly Arg Asn Phe Arg Asn Pro Leu 420 425 430 Ala Lys <210> 52 <211> 108 <212> PRT <213> Homo sapiens <400> 52 Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Asn Thr Trp 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Met 35 40 45 Tyr Lys Ala Ser Ser Leu Glu Ser Gly Val Pro Ser Arg Phe Ile Gly 50 55 60 Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Ser Asp Ser Lys 85 90 95 Met Phe Gly Gln Gly Thr Lys Val Glu Val Lys Gly 100 105 <210> 53 <211> 386 <212> PRT <213> Homo sapiens <400> 53 Met Phe Ala Glu Ile Gln Ile Gln Asp Lys Asp Arg Met Gly Thr Ala 1 5 10 15 Gly Lys Val Ile Lys Cys Lys Ala Ala Val Leu Trp Glu Gln Lys Gln 20 25 30 Pro Phe Ser Ile Glu Glu Ile Glu Val Ala Pro Pro Lys Thr Lys Glu 35 40 45 Val Arg Ile Lys Ile Leu Ala Thr Gly Ile Cys Arg Thr Asp Asp His 50 55 60 Val Ile Lys Gly Thr Met Val Ser Lys Phe Pro Val Ile Val Gly His 65 70 75 80 Glu Ala Thr Gly Ile Val Glu Ser Ile Gly Glu Gly Val Thr Thr Val 85 90 95 Lys Pro Gly Asp Lys Val Ile Pro Leu Phe Leu Pro Gln Cys Arg Glu 100 105 110 Cys Asn Ala Cys Arg Asn Pro Asp Gly Asn Leu Cys Ile Arg Ser Asp 115 120 125 Ile Thr Gly Arg Gly Val Leu Ala Asp Gly Thr Thr Arg Phe Thr Cys 130 135 140 Lys Gly Lys Pro Val His His Phe Met Asn Thr Ser Thr Phe Thr Glu 145 150 155 160 Tyr Thr Val Val Asp Glu Ser Ser Val Ala Lys Ile Asp Asp Ala Ala 165 170 175 Pro Pro Glu Lys Val Cys Leu Ile Gly Cys Gly Phe Ser Thr Gly Tyr 180 185 190 Gly Ala Ala Val Lys Thr Gly Lys Val Lys Pro Gly Ser Thr Cys Val 195 200 205 Val Phe Gly Leu Gly Gly Val Gly Leu Ser Val Ile Met Gly Cys Lys 210 215 220 Ser Ala Gly Ala Ser Arg Ile Ile Gly Ile Asp Leu Asn Lys Asp Lys 225 230 235 240 Phe Glu Lys Ala Met Ala Val Gly Ala Thr Glu Cys Ile Ser Pro Lys 245 250 255 Asp Ser Thr Lys Pro Ile Ser Glu Val Leu Ser Glu Met Thr Gly Asn 260 265 270 Asn Val Gly Tyr Thr Phe Glu Val Ile Gly His Leu Glu Thr Met Ile 275 280 285 Asp Ala Leu Ala Ser Cys His Met Asn Tyr Gly Thr Ser Val Val Val 290 295 300 Gly Val Pro Pro Ser Ala Lys Met Leu Thr Tyr Asp Pro Met Leu Leu 305 310 315 320 Phe Thr Gly Arg Thr Trp Lys Gly Cys Val Phe Gly Gly Leu Lys Ser 325 330 335 Arg Asp Asp Val Pro Lys Leu Val Thr Glu Phe Leu Ala Lys Lys Phe 340 345 350 Asp Leu Asp Gln Leu Ile Thr His Val Leu Pro Phe Lys Lys Ile Ser 355 360 365 Glu Gly Phe Glu Leu Leu Asn Ser Gly Gln Ser Ile Arg Thr Val Leu 370 375 380 Thr Phe 385 <210> 54 <211> 352 <212> PRT <213> Homo sapiens <400> 54 Met Arg Ser Leu Gly Ala Leu Leu Leu Leu Leu Ser Ala Cys Leu Ala 1 5 10 15 Val Ser Ala Gly Pro Val Pro Thr Pro Pro Asp Asn Ile Gln Val Gln 20 25 30 Glu Asn Phe Asn Ile Ser Arg Ile Tyr Gly Lys Trp Tyr Asn Leu Ala 35 40 45 Ile Gly Ser Thr Cys Pro Trp Leu Lys Lys Ile Met Asp Arg Met Thr 50 55 60 Val Ser Thr Leu Val Leu Gly Glu Gly Ala Thr Glu Ala Glu Ile Ser 65 70 75 80 Met Thr Ser Thr Arg Trp Arg Lys Gly Val Cys Glu Glu Thr Ser Gly 85 90 95 Ala Tyr Glu Lys Thr Asp Thr Asp Gly Lys Phe Leu Tyr His Lys Ser 100 105 110 Lys Trp Asn Ile Thr Met Glu Ser Tyr Val Val His Thr Asn Tyr Asp 115 120 125 Glu Tyr Ala Ile Phe Leu Thr Lys Lys Phe Ser Arg His His Gly Pro 130 135 140 Thr Ile Thr Ala Lys Leu Tyr Gly Arg Ala Pro Gln Leu Arg Glu Thr 145 150 155 160 Leu Leu Gln Asp Phe Arg Val Val Ala Gln Gly Val Gly Ile Pro Glu 165 170 175 Asp Ser Ile Phe Thr Met Ala Asp Arg Gly Glu Cys Val Pro Gly Glu 180 185 190 Gln Glu Pro Glu Pro Ile Leu Ile Pro Arg Val Arg Arg Ala Val Leu 195 200 205 Pro Gln Glu Glu Glu Gly Ser Gly Gly Gly Gln Leu Val Thr Glu Val 210 215 220 Thr Lys Lys Glu Asp Ser Cys Gln Leu Gly Tyr Ser Ala Gly Pro Cys 225 230 235 240 Met Gly Met Thr Ser Arg Tyr Phe Tyr Asn Gly Thr Ser Met Ala Cys 245 250 255 Glu Thr Phe Gln Tyr Gly Gly Cys Met Gly Asn Gly Asn Asn Phe Val 260 265 270 Thr Glu Lys Glu Cys Leu Gln Thr Cys Arg Thr Val Ala Ala Cys Asn 275 280 285 Leu Pro Ile Val Arg Gly Pro Cys Arg Ala Phe Ile Gln Leu Trp Ala 290 295 300 Phe Asp Ala Val Lys Gly Lys Cys Val Leu Phe Pro Tyr Gly Gly Cys 305 310 315 320 Gln Gly Asn Gly Asn Lys Phe Tyr Ser Glu Lys Glu Cys Arg Glu Tyr 325 330 335 Cys Gly Val Pro Gly Asp Gly Asp Glu Glu Leu Leu Arg Phe Ser Asn 340 345 350 <210> 55 <211> 485 <212> PRT <213> Homo sapiens <400> 55 Met Arg Lys Arg Ala Pro Gln Ser Glu Met Ala Pro Ala Gly Val Ser 1 5 10 15 Leu Arg Ala Thr Ile Leu Cys Leu Leu Ala Trp Ala Gly Leu Ala Ala 20 25 30 Gly Asp Arg Val Tyr Ile His Pro Phe His Leu Val Ile His Asn Glu 35 40 45 Ser Thr Cys Glu Gln Leu Ala Lys Ala Asn Ala Gly Lys Pro Lys Asp 50 55 60 Pro Thr Phe Ile Pro Ala Pro Ile Gln Ala Lys Thr Ser Pro Val Asp 65 70 75 80 Glu Lys Ala Leu Gln Asp Gln Leu Val Leu Val Ala Ala Lys Leu Asp 85 90 95 Thr Glu Asp Lys Leu Arg Ala Ala Met Val Gly Met Leu Ala Asn Phe 100 105 110 Leu Gly Phe Arg Ile Tyr Gly Met His Ser Glu Leu Trp Gly Val Val 115 120 125 His Gly Ala Thr Val Leu Ser Pro Thr Ala Val Phe Gly Thr Leu Ala 130 135 140 Ser Leu Tyr Leu Gly Ala Leu Asp His Thr Ala Asp Arg Leu Gln Ala 145 150 155 160 Ile Leu Gly Val Pro Trp Lys Asp Lys Asn Cys Thr Ser Arg Leu Asp 165 170 175 Ala His Lys Val Leu Ser Ala Leu Gln Ala Val Gln Gly Leu Leu Val 180 185 190 Ala Gln Gly Arg Ala Asp Ser Gln Ala Gln Leu Leu Leu Ser Thr Val 195 200 205 Val Gly Val Phe Thr Ala Pro Gly Leu His Leu Lys Gln Pro Phe Val 210 215 220 Gln Gly Leu Ala Leu Tyr Thr Pro Val Val Leu Pro Arg Ser Leu Asp 225 230 235 240 Phe Thr Glu Leu Asp Val Ala Ala Glu Lys Ile Asp Arg Phe Met Gln 245 250 255 Ala Val Thr Gly Trp Lys Thr Gly Cys Ser Leu Met Gly Ala Ser Val 260 265 270 Asp Ser Thr Leu Ala Phe Asn Thr Tyr Val His Phe Gln Gly Lys Met 275 280 285 Lys Gly Phe Ser Leu Leu Ala Glu Pro Gln Glu Phe Trp Val Asp Asn 290 295 300 Ser Thr Ser Val Ser Val Pro Met Leu Ser Gly Met Gly Thr Phe Gln 305 310 315 320 His Trp Ser Asp Ile Gln Asp Asn Phe Ser Val Thr Gln Val Pro Phe 325 330 335 Thr Glu Ser Ala Cys Leu Leu Leu Ile Gln Pro His Tyr Ala Ser Asp 340 345 350 Leu Asp Lys Val Glu Gly Leu Thr Phe Gln Gln Asn Ser Leu Asn Trp 355 360 365 Met Lys Lys Leu Ser Pro Arg Thr Ile His Leu Thr Met Pro Gln Leu 370 375 380 Val Leu Gln Gly Ser Tyr Asp Leu Gln Asp Leu Leu Ala Gln Ala Glu 385 390 395 400 Leu Pro Ala Ile Leu His Thr Glu Leu Asn Leu Gln Lys Leu Ser Asn 405 410 415 Asp Arg Ile Arg Val Gly Glu Val Leu Asn Ser Ile Phe Phe Glu Leu 420 425 430 Glu Ala Asp Glu Arg Glu Pro Thr Glu Ser Thr Gln Gln Leu Asn Lys 435 440 445 Pro Glu Val Leu Glu Val Thr Leu Asn Arg Pro Phe Leu Phe Ala Val 450 455 460 Tyr Asp Gln Ser Ala Thr Ala Leu His Phe Leu Gly Arg Val Ala Asn 465 470 475 480 Pro Leu Ser Thr Ala 485 <210> 56 <211> 464 <212> PRT <213> Homo sapiens <400> 56 Met Tyr Ser Asn Val Ile Gly Thr Val Thr Ser Gly Lys Arg Lys Val 1 5 10 15 Tyr Leu Leu Ser Leu Leu Leu Ile Gly Phe Trp Asp Cys Val Thr Cys 20 25 30 His Gly Ser Pro Val Asp Ile Cys Thr Ala Lys Pro Arg Asp Ile Pro 35 40 45 Met Asn Pro Met Cys Ile Tyr Arg Ser Pro Glu Lys Lys Ala Thr Glu 50 55 60 Asp Glu Gly Ser Glu Gln Lys Ile Pro Glu Ala Thr Asn Arg Arg Val 65 70 75 80 Trp Glu Leu Ser Lys Ala Asn Ser Arg Phe Ala Thr Thr Phe Tyr Gln 85 90 95 His Leu Ala Asp Ser Lys Asn Asp Asn Asp Asn Ile Phe Leu Ser Pro 100 105 110 Leu Ser Ile Ser Thr Ala Phe Ala Met Thr Lys Leu Gly Ala Cys Asn 115 120 125 Asp Thr Leu Gln Gln Leu Met Glu Val Phe Lys Phe Asp Thr Ile Ser 130 135 140 Glu Lys Thr Ser Asp Gln Ile His Phe Phe Phe Ala Lys Leu Asn Cys 145 150 155 160 Arg Leu Tyr Arg Lys Ala Asn Lys Ser Ser Lys Leu Val Ser Ala Asn 165 170 175 Arg Leu Phe Gly Asp Lys Ser Leu Thr Phe Asn Glu Thr Tyr Gln Asp 180 185 190 Ile Ser Glu Leu Val Tyr Gly Ala Lys Leu Gln Pro Leu Asp Phe Lys 195 200 205 Glu Asn Ala Glu Gln Ser Arg Ala Ala Ile Asn Lys Trp Val Ser Asn 210 215 220 Lys Thr Glu Gly Arg Ile Thr Asp Val Ile Pro Ser Glu Ala Ile Asn 225 230 235 240 Glu Leu Thr Val Leu Val Leu Val Asn Thr Ile Tyr Phe Lys Gly Leu 245 250 255 Trp Lys Ser Lys Phe Ser Pro Glu Asn Thr Arg Lys Glu Leu Phe Tyr 260 265 270 Lys Ala Asp Gly Glu Ser Cys Ser Ala Ser Met Met Tyr Gln Glu Gly 275 280 285 Lys Phe Arg Tyr Arg Arg Val Ala Glu Gly Thr Gln Val Leu Glu Leu 290 295 300 Pro Phe Lys Gly Asp Asp Ile Thr Met Val Leu Ile Leu Pro Lys Pro 305 310 315 320 Glu Lys Ser Leu Ala Lys Val Glu Lys Glu Leu Thr Pro Glu Val Leu 325 330 335 Gln Glu Trp Leu Asp Glu Leu Glu Glu Met Met Leu Val Val His Met 340 345 350 Pro Arg Phe Arg Ile Glu Asp Gly Phe Ser Leu Lys Glu Gln Leu Gln 355 360 365 Asp Met Gly Leu Val Asp Leu Phe Ser Pro Glu Lys Ser Lys Leu Pro 370 375 380 Gly Ile Val Ala Glu Gly Arg Asp Asp Leu Tyr Val Ser Asp Ala Phe 385 390 395 400 His Lys Ala Phe Leu Glu Val Asn Glu Glu Gly Ser Glu Ala Ala Ala 405 410 415 Ser Thr Ala Val Val Ile Ala Gly Arg Ser Leu Asn Pro Asn Arg Val 420 425 430 Thr Phe Lys Ala Asn Arg Pro Phe Leu Val Phe Ile Arg Glu Val Pro 435 440 445 Leu Asn Thr Ile Ile Phe Met Gly Arg Val Ala Asn Pro Cys Val Lys 450 455 460 <210> 57 <211> 100 <212> PRT <213> Homo sapiens <400> 57 Met Lys Leu Leu Ala Ala Thr Val Leu Leu Leu Thr Ile Cys Ser Leu 1 5 10 15 Glu Gly Ala Leu Val Arg Arg Gln Ala Lys Glu Pro Cys Val Glu Ser 20 25 30 Leu Val Ser Gln Tyr Phe Gln Thr Val Thr Asp Tyr Gly Lys Asp Leu 35 40 45 Met Glu Lys Val Lys Ser Pro Glu Leu Gln Ala Glu Ala Lys Ser Tyr 50 55 60 Phe Glu Lys Ser Lys Glu Gln Leu Thr Pro Leu Ile Lys Lys Ala Gly 65 70 75 80 Thr Glu Leu Val Asn Phe Leu Ser Tyr Phe Val Glu Leu Gly Thr Gln 85 90 95 Pro Ala Thr Gln 100 <210> 58 <211> 345 <212> PRT <213> Homo sapiens <400> 58 Met Ile Ser Pro Val Leu Ile Leu Phe Ser Ser Phe Leu Cys His Val 1 5 10 15 Ala Ile Ala Gly Arg Thr Cys Pro Lys Pro Asp Asp Leu Pro Phe Ser 20 25 30 Thr Val Val Pro Leu Lys Thr Phe Tyr Glu Pro Gly Glu Glu Ile Thr 35 40 45 Tyr Ser Cys Lys Pro Gly Tyr Val Ser Arg Gly Gly Met Arg Lys Phe 50 55 60 Ile Cys Pro Leu Thr Gly Leu Trp Pro Ile Asn Thr Leu Lys Cys Thr 65 70 75 80 Pro Arg Val Cys Pro Phe Ala Gly Ile Leu Glu Asn Gly Ala Val Arg 85 90 95 Tyr Thr Thr Phe Glu Tyr Pro Asn Thr Ile Ser Phe Ser Cys Asn Thr 100 105 110 Gly Phe Tyr Leu Asn Gly Ala Asp Ser Ala Lys Cys Thr Glu Glu Gly 115 120 125 Lys Trp Ser Pro Glu Leu Pro Val Cys Ala Pro Ile Ile Cys Pro Pro 130 135 140 Pro Ser Ile Pro Thr Phe Ala Thr Leu Arg Val Tyr Lys Pro Ser Ala 145 150 155 160 Gly Asn Asn Ser Leu Tyr Arg Asp Thr Ala Val Phe Glu Cys Leu Pro 165 170 175 Gln His Ala Met Phe Gly Asn Asp Thr Ile Thr Cys Thr Thr His Gly 180 185 190 Asn Trp Thr Lys Leu Pro Glu Cys Arg Glu Val Lys Cys Pro Phe Pro 195 200 205 Ser Arg Pro Asp Asn Gly Phe Val Asn Tyr Pro Ala Lys Pro Thr Leu 210 215 220 Tyr Tyr Lys Asp Lys Ala Thr Phe Gly Cys His Asp Gly Tyr Ser Leu 225 230 235 240 Asp Gly Pro Glu Glu Ile Glu Cys Thr Lys Leu Gly Asn Trp Ser Ala 245 250 255 Met Pro Ser Cys Lys Ala Ser Cys Lys Val Pro Val Lys Lys Ala Thr 260 265 270 Val Val Tyr Gln Gly Glu Arg Val Lys Ile Gln Glu Lys Phe Lys Asn 275 280 285 Gly Met Leu His Gly Asp Lys Val Ser Phe Phe Cys Lys Asn Lys Glu 290 295 300 Lys Lys Cys Ser Tyr Thr Glu Asp Ala Gln Cys Ile Asp Gly Thr Ile 305 310 315 320 Glu Val Pro Lys Cys Phe Lys Glu His Ser Ser Leu Ala Phe Trp Lys 325 330 335 Thr Asp Ala Ser Asp Val Lys Pro Cys 340 345 <210> 59 <211> 694 <212> PRT <213> Homo sapiens <400> 59 Met Glu Gly Pro His Leu Pro Asn Lys Lys Lys His Lys Lys Gln Ala 1 5 10 15 Val Lys Thr Glu Pro Glu Lys Lys Ser Gln Ser Thr Lys Leu Ser Val 20 25 30 Val His Glu Lys Lys Ser Gln Glu Gly Lys Pro Lys Glu His Thr Glu 35 40 45 Pro Lys Ser Leu Pro Lys Gln Ala Ser Asp Thr Gly Ser Asn Asp Ala 50 55 60 His Asn Lys Lys Ala Val Ser Arg Ser Ala Glu Gln Gln Pro Ser Glu 65 70 75 80 Lys Ser Thr Glu Pro Lys Thr Lys Pro Gln Asp Met Ile Ser Ala Gly 85 90 95 Gly Glu Ser Val Ala Gly Ile Thr Ala Ile Ser Gly Lys Pro Gly Asp 100 105 110 Lys Lys Lys Glu Lys Lys Ser Leu Thr Pro Ala Val Pro Val Glu Ser 115 120 125 Lys Pro Asp Lys Pro Ser Gly Lys Ser Gly Met Asp Ala Ala Leu Asp 130 135 140 Asp Leu Ile Asp Thr Leu Gly Gly Pro Glu Glu Thr Glu Glu Glu Asn 145 150 155 160 Thr Thr Tyr Thr Gly Pro Glu Val Ser Asp Pro Met Ser Ser Thr Tyr 165 170 175 Ile Glu Glu Leu Gly Lys Arg Glu Val Thr Ile Pro Pro Lys Tyr Arg 180 185 190 Glu Leu Leu Ala Lys Lys Glu Gly Ile Thr Gly Pro Pro Ala Asp Ser 195 200 205 Ser Lys Pro Ile Gly Pro Asp Asp Ala Ile Asp Ala Leu Ser Ser Asp 210 215 220 Phe Thr Cys Gly Ser Pro Thr Ala Ala Gly Lys Lys Thr Glu Lys Glu 225 230 235 240 Glu Ser Thr Glu Val Leu Lys Ala Gln Ser Ala Gly Thr Val Arg Ser 245 250 255 Ala Ala Pro Pro Gln Glu Lys Lys Arg Lys Val Glu Lys Asp Thr Met 260 265 270 Ser Asp Gln Ala Leu Glu Ala Leu Ser Ala Ser Leu Gly Thr Arg Gln 275 280 285 Ala Glu Pro Glu Leu Asp Leu Arg Ser Ile Lys Glu Val Asp Glu Ala 290 295 300 Lys Ala Lys Glu Glu Lys Leu Glu Lys Cys Gly Glu Asp Asp Glu Thr 305 310 315 320 Ile Pro Ser Glu Tyr Arg Leu Lys Pro Ala Thr Asp Lys Asp Gly Lys 325 330 335 Pro Leu Leu Pro Glu Pro Glu Glu Lys Pro Lys Pro Arg Ser Glu Ser 340 345 350 Glu Leu Ile Asp Glu Leu Ser Glu Asp Phe Asp Arg Ser Glu Cys Lys 355 360 365 Glu Lys Pro Ser Lys Pro Thr Glu Lys Thr Glu Glu Ser Lys Ala Ala 370 375 380 Ala Pro Ala Pro Val Ser Glu Ala Val Cys Arg Thr Ser Met Cys Ser 385 390 395 400 Ile Gln Ser Ala Pro Pro Glu Pro Ala Thr Leu Lys Gly Thr Val Pro 405 410 415 Asp Asp Ala Val Glu Ala Leu Ala Asp Ser Leu Gly Lys Lys Glu Ala 420 425 430 Asp Pro Glu Asp Gly Lys Pro Val Met Asp Lys Val Lys Glu Lys Ala 435 440 445 Lys Glu Glu Asp Arg Glu Lys Leu Gly Glu Lys Glu Glu Thr Ile Pro 450 455 460 Pro Asp Tyr Arg Leu Glu Glu Val Lys Asp Lys Asp Gly Lys Pro Leu 465 470 475 480 Leu Pro Lys Glu Ser Lys Glu Gln Leu Pro Pro Met Ser Glu Asp Phe 485 490 495 Leu Leu Asp Ala Leu Ser Glu Asp Phe Ser Gly Pro Gln Asn Ala Ser 500 505 510 Ser Leu Lys Phe Glu Asp Ala Lys Leu Ala Ala Ala Ile Ser Glu Val 515 520 525 Val Ser Gln Thr Pro Ala Ser Thr Thr Gln Ala Gly Ala Pro Pro Arg 530 535 540 Asp Thr Ser Gln Ser Asp Lys Asp Leu Asp Asp Ala Leu Asp Lys Leu 545 550 555 560 Ser Asp Ser Leu Gly Gln Arg Gln Pro Asp Pro Asp Glu Asn Lys Pro 565 570 575 Met Glu Asp Lys Val Lys Glu Lys Ala Lys Ala Glu His Arg Asp Lys 580 585 590 Leu Gly Glu Arg Asp Asp Thr Ile Pro Pro Glu Tyr Arg His Leu Leu 595 600 605 Asp Asp Asn Gly Gln Asp Lys Pro Val Lys Pro Pro Thr Lys Lys Ser 610 615 620 Glu Asp Ser Lys Lys Pro Ala Asp Asp Gln Asp Pro Ile Asp Ala Leu 625 630 635 640 Ser Gly Asp Leu Asp Ser Cys Pro Ser Thr Thr Glu Thr Ser Gln Asn 645 650 655 Thr Ala Lys Asp Lys Cys Lys Lys Ala Ala Ser Ser Ser Lys Ala Pro 660 665 670 Lys Asn Gly Gly Lys Ala Lys Asp Ser Ala Lys Thr Thr Glu Glu Thr 675 680 685 Ser Lys Pro Lys Asp Asp 690 <210> 60 <211> 227 <212> PRT <213> Homo sapiens <400> 60 Met Gly Gly Lys Leu Ser Lys Lys Lys Lys Gly Tyr Asn Val Asn Asp 1 5 10 15 Glu Lys Ala Lys Glu Lys Asp Lys Lys Ala Glu Gly Ala Ala Thr Glu 20 25 30 Glu Glu Gly Thr Pro Lys Glu Ser Glu Pro Gln Ala Ala Ala Glu Pro 35 40 45 Ala Glu Ala Lys Glu Gly Lys Glu Lys Pro Asp Gln Asp Ala Glu Gly 50 55 60 Lys Ala Glu Glu Lys Glu Gly Glu Lys Asp Ala Ala Ala Ala Lys Glu 65 70 75 80 Glu Ala Pro Lys Ala Glu Pro Glu Lys Thr Glu Gly Ala Ala Glu Ala 85 90 95 Lys Ala Glu Pro Pro Lys Ala Pro Glu Gln Glu Gln Ala Ala Pro Gly 100 105 110 Pro Ala Ala Gly Gly Glu Ala Pro Lys Ala Ala Glu Ala Ala Ala Ala 115 120 125 Pro Ala Glu Ser Ala Ala Pro Ala Ala Gly Glu Glu Pro Ser Lys Glu 130 135 140 Glu Gly Glu Pro Lys Lys Thr Glu Ala Pro Ala Ala Pro Ala Ala Gln 145 150 155 160 Glu Thr Lys Ser Asp Gly Ala Pro Ala Ser Asp Ser Lys Pro Gly Ser 165 170 175 Ser Glu Ala Ala Pro Ser Ser Lys Glu Thr Pro Ala Ala Thr Glu Ala 180 185 190 Pro Ser Ser Thr Pro Lys Ala Gln Gly Pro Ala Ala Ser Ala Glu Glu 195 200 205 Pro Lys Pro Val Glu Ala Pro Ala Ala Asn Ser Asp Gln Thr Val Thr 210 215 220 Val Lys Glu 225 <210> 61 <211> 368 <212> PRT <213> Homo sapiens <400> 61 Met Lys Ser Leu Val Leu Leu Leu Cys Leu Ala Gln Leu Trp Gly Cys 1 5 10 15 His Ser Ala Pro His Gly Pro Gly Leu Ile Tyr Arg Gln Pro Asn Cys 20 25 30 Asp Asp Pro Glu Thr Glu Glu Ala Ala Leu Val Ala Ile Asp Tyr Ile 35 40 45 Asn Gln Asn Leu Pro Trp Gly Tyr Lys His Thr Leu Asn Gln Ile Asp 50 55 60 Glu Val Lys Val Trp Pro Gln Gln Pro Ser Gly Glu Leu Phe Glu Ile 65 70 75 80 Glu Ile Asp Thr Leu Glu Thr Thr Cys His Val Leu Asp Pro Thr Pro 85 90 95 Val Ala Arg Cys Ser Val Arg Gln Leu Lys Glu His Ala Val Glu Gly 100 105 110 Asp Cys Asp Phe Gln Leu Leu Lys Leu Asp Gly Lys Phe Ser Val Val 115 120 125 Tyr Ala Lys Cys Asp Ser Ser Pro Ala Asp Ser Ala Glu Asp Val Arg 130 135 140 Lys Val Cys Gln Asp Cys Pro Leu Leu Ala Pro Leu Asn Asp Thr Arg 145 150 155 160 Val Val His Ala Ala Lys Ala Ala Leu Ala Ala Phe Asn Ala Gln Asn 165 170 175 Asn Gly Ser Asn Phe Gln Leu Glu Glu Ile Ser Arg Ala Gln Leu Val 180 185 190 Pro Leu Pro Pro Ser Thr Tyr Val Glu Phe Thr Val Ser Gly Thr Asp 195 200 205 Cys Val Ala Lys Glu Ala Thr Glu Ala Ala Lys Cys Asn Leu Leu Ala 210 215 220 Glu Lys Gln Tyr Gly Phe Cys Lys Ala Thr Leu Ser Glu Lys Leu Gly 225 230 235 240 Gly Ala Glu Val Ala Val Thr Cys Met Val Phe Gln Thr Gln Pro Val 245 250 255 Ser Ser Gln Pro Gln Pro Glu Gly Ala Asn Glu Ala Val Pro Thr Pro 260 265 270 Val Val Asp Pro Asp Ala Pro Pro Ser Pro Pro Leu Gly Ala Pro Gly 275 280 285 Leu Pro Pro Ala Gly Ser Pro Pro Asp Ser His Val Leu Leu Ala Ala 290 295 300 Pro Pro Gly His Gln Leu His Arg Ala His Tyr Asp Leu Arg His Thr 305 310 315 320 Phe Met Gly Val Val Ser Leu Gly Ser Pro Ser Gly Glu Val Ser His 325 330 335 Pro Arg Lys Thr Arg Thr Val Val Gln Pro Ser Val Gly Ala Ala Ala 340 345 350 Gly Pro Val Val Pro Pro Cys Pro Gly Arg Ile Arg His Phe Lys Val 355 360 365 <210> 62 <211> 417 <212> PRT <213> Homo sapiens <400> 62 Met Leu Leu Ser Val Pro Leu Leu Leu Gly Leu Leu Gly Leu Ala Val 1 5 10 15 Ala Glu Pro Ala Val Tyr Phe Lys Glu Gln Phe Leu Asp Gly Asp Gly 20 25 30 Trp Thr Ser Arg Trp Ile Glu Ser Lys His Lys Ser Asp Phe Gly Lys 35 40 45 Phe Val Leu Ser Ser Gly Lys Phe Tyr Gly Asp Glu Glu Lys Asp Lys 50 55 60 Gly Leu Gln Thr Ser Gln Asp Ala Arg Phe Tyr Ala Leu Ser Ala Ser 65 70 75 80 Phe Glu Pro Phe Ser Asn Lys Gly Gln Thr Leu Val Val Gln Phe Thr 85 90 95 Val Lys His Glu Gln Asn Ile Asp Cys Gly Gly Gly Tyr Val Lys Leu 100 105 110 Phe Pro Asn Ser Leu Asp Gln Thr Asp Met His Gly Asp Ser Glu Tyr 115 120 125 Asn Ile Met Phe Gly Pro Asp Ile Cys Gly Pro Gly Thr Lys Lys Val 130 135 140 His Val Ile Phe Asn Tyr Lys Gly Lys Asn Val Leu Ile Asn Lys Asp 145 150 155 160 Ile Arg Cys Lys Asp Asp Glu Phe Thr His Leu Tyr Thr Leu Ile Val 165 170 175 Arg Pro Asp Asn Thr Tyr Glu Val Lys Ile Asp Asn Ser Gln Val Glu 180 185 190 Ser Gly Ser Leu Glu Asp Asp Trp Asp Phe Leu Pro Pro Lys Lys Ile 195 200 205 Lys Asp Pro Asp Ala Ser Lys Pro Glu Asp Trp Asp Glu Arg Ala Lys 210 215 220 Ile Asp Asp Pro Thr Asp Ser Lys Pro Glu Asp Trp Asp Lys Pro Glu 225 230 235 240 His Ile Pro Asp Pro Asp Ala Lys Lys Pro Glu Asp Trp Asp Glu Glu 245 250 255 Met Asp Gly Glu Trp Glu Pro Pro Val Ile Gln Asn Pro Glu Tyr Lys 260 265 270 Gly Glu Trp Lys Pro Arg Gln Ile Asp Asn Pro Asp Tyr Lys Gly Thr 275 280 285 Trp Ile His Pro Glu Ile Asp Asn Pro Glu Tyr Ser Pro Asp Pro Ser 290 295 300 Ile Tyr Ala Tyr Asp Asn Phe Gly Val Leu Gly Leu Asp Leu Trp Gln 305 310 315 320 Val Lys Ser Gly Thr Ile Phe Asp Asn Phe Leu Ile Thr Asn Asp Glu 325 330 335 Ala Tyr Ala Glu Glu Phe Gly Asn Glu Thr Trp Gly Val Thr Lys Ala 340 345 350 Ala Glu Lys Gln Met Lys Asp Lys Gln Asp Glu Glu Gln Arg Leu Lys 355 360 365 Glu Glu Glu Glu Asp Lys Lys Arg Lys Glu Glu Glu Glu Ala Glu Asp 370 375 380 Lys Glu Asp Asp Glu Asp Lys Asp Glu Asp Glu Glu Asp Glu Glu Asp 385 390 395 400 Lys Glu Glu Asp Glu Glu Glu Asp Val Pro Gly Gln Ala Lys Asp Glu 405 410 415 Leu <210> 63 <211> 714 <212> PRT <213> Homo sapiens <400> 63 Met Ser Glu Glu Ile Ile Thr Pro Val Tyr Cys Thr Gly Val Ser Ala 1 5 10 15 Gln Val Gln Lys Gln Arg Ala Arg Glu Leu Gly Leu Gly Arg His Glu 20 25 30 Asn Ala Ile Lys Tyr Leu Gly Gln Asp Tyr Glu Gln Leu Arg Val Arg 35 40 45 Cys Leu Gln Ser Gly Thr Leu Phe Arg Asp Glu Ala Phe Pro Pro Val 50 55 60 Pro Gln Ser Leu Gly Tyr Lys Asp Leu Gly Pro Asn Ser Ser Lys Thr 65 70 75 80 Tyr Gly Ile Lys Trp Lys Arg Pro Thr Glu Leu Leu Ser Asn Pro Gln 85 90 95 Phe Ile Val Asp Gly Ala Thr Arg Thr Asp Ile Cys Gln Gly Ala Leu 100 105 110 Gly Asp Cys Trp Leu Leu Ala Ala Ile Ala Ser Leu Thr Leu Asn Asp 115 120 125 Thr Leu Leu His Arg Val Val Pro His Gly Gln Ser Phe Gln Asn Gly 130 135 140 Tyr Ala Gly Ile Phe His Phe Gln Leu Trp Gln Phe Gly Glu Trp Val 145 150 155 160 Asp Val Val Val Asp Asp Leu Leu Pro Ile Lys Asp Gly Lys Leu Val 165 170 175 Phe Val His Ser Ala Glu Gly Asn Glu Phe Trp Ser Ala Leu Leu Glu 180 185 190 Lys Ala Tyr Ala Lys Val Asn Gly Ser Tyr Glu Ala Leu Ser Gly Gly 195 200 205 Ser Thr Ser Glu Gly Phe Glu Asp Phe Thr Gly Gly Val Thr Glu Trp 210 215 220 Tyr Glu Leu Arg Lys Ala Pro Ser Asp Leu Tyr Gln Ile Ile Leu Lys 225 230 235 240 Ala Leu Glu Arg Gly Ser Leu Leu Gly Cys Ser Ile Asp Ile Ser Ser 245 250 255 Val Leu Asp Met Glu Ala Ile Thr Phe Lys Lys Leu Val Lys Gly His 260 265 270 Ala Tyr Ser Val Thr Gly Ala Lys Gln Val Asn Tyr Arg Gly Gln Val 275 280 285 Val Ser Leu Ile Arg Met Arg Asn Pro Trp Gly Glu Val Glu Trp Thr 290 295 300 Gly Ala Trp Ser Asp Ser Ser Ser Glu Trp Asn Asn Val Asp Pro Tyr 305 310 315 320 Glu Arg Asp Gln Leu Arg Val Lys Met Glu Asp Gly Glu Phe Trp Met 325 330 335 Ser Phe Arg Asp Phe Met Arg Glu Phe Thr Arg Leu Glu Ile Cys Asn 340 345 350 Leu Thr Pro Asp Ala Leu Lys Ser Arg Thr Ile Arg Lys Trp Asn Thr 355 360 365 Thr Leu Tyr Glu Gly Thr Trp Arg Arg Gly Ser Thr Ala Gly Gly Cys 370 375 380 Arg Asn Tyr Pro Ala Thr Phe Trp Val Asn Pro Gln Phe Lys Ile Arg 385 390 395 400 Leu Asp Glu Thr Asp Asp Pro Asp Asp Tyr Gly Asp Arg Glu Ser Gly 405 410 415 Cys Ser Phe Val Leu Ala Leu Met Gln Lys His Arg Arg Arg Glu Arg 420 425 430 Arg Phe Gly Arg Asp Met Glu Thr Ile Gly Phe Ala Val Tyr Glu Val 435 440 445 Pro Pro Glu Leu Val Gly Gln Pro Ala Val His Leu Lys Arg Asp Phe 450 455 460 Phe Leu Ala Asn Ala Ser Arg Ala Arg Ser Glu Gln Phe Ile Asn Leu 465 470 475 480 Arg Glu Val Ser Thr Arg Phe Arg Leu Pro Pro Gly Glu Tyr Val Val 485 490 495 Val Pro Ser Thr Phe Glu Pro Asn Lys Glu Gly Asp Phe Val Leu Arg 500 505 510 Phe Phe Ser Glu Lys Ser Ala Gly Thr Val Glu Leu Asp Asp Gln Ile 515 520 525 Gln Ala Asn Leu Pro Asp Glu Gln Val Leu Ser Glu Glu Glu Ile Asp 530 535 540 Glu Asn Phe Lys Ala Leu Phe Arg Gln Leu Ala Gly Glu Asp Met Glu 545 550 555 560 Ile Ser Val Lys Glu Leu Arg Thr Ile Leu Asn Arg Ile Ile Ser Lys 565 570 575 His Lys Asp Leu Arg Thr Lys Gly Phe Ser Leu Glu Ser Cys Arg Ser 580 585 590 Met Val Asn Leu Met Asp Arg Asp Gly Asn Gly Lys Leu Gly Leu Val 595 600 605 Glu Phe Asn Ile Leu Trp Asn Arg Ile Arg Asn Tyr Leu Ser Ile Phe 610 615 620 Arg Lys Phe Asp Leu Asp Lys Ser Gly Ser Met Ser Ala Tyr Glu Met 625 630 635 640 Arg Met Ala Ile Glu Ser Ala Gly Phe Lys Leu Asn Lys Lys Leu Tyr 645 650 655 Glu Leu Ile Ile Thr Arg Tyr Ser Glu Pro Asp Leu Ala Val Asp Phe 660 665 670 Asp Asn Phe Val Cys Cys Leu Val Arg Leu Glu Thr Met Phe Arg Phe 675 680 685 Phe Lys Thr Leu Asp Thr Asp Leu Asp Gly Val Val Thr Phe Asp Leu 690 695 700 Phe Lys Trp Leu Gln Leu Thr Met Phe Ala 705 710 <210> 64 <211> 191 <212> PRT <213> Homo sapiens <400> 64 Met Gln Thr Ile Lys Cys Val Val Val Gly Asp Gly Ala Val Gly Lys 1 5 10 15 Thr Cys Leu Leu Ile Ser Tyr Thr Thr Asn Lys Phe Pro Ser Glu Tyr 20 25 30 Val Pro Thr Val Phe Asp Asn Tyr Ala Val Thr Val Met Ile Gly Gly 35 40 45 Glu Pro Tyr Thr Leu Gly Leu Phe Asp Thr Ala Gly Gln Glu Asp Tyr 50 55 60 Asp Arg Leu Arg Pro Leu Ser Tyr Pro Gln Thr Asp Val Phe Leu Val 65 70 75 80 Cys Phe Ser Val Val Ser Pro Ser Ser Phe Glu Asn Val Lys Glu Lys 85 90 95 Trp Val Pro Glu Ile Thr His His Cys Pro Lys Thr Pro Phe Leu Leu 100 105 110 Val Gly Thr Gln Ile Asp Leu Arg Asp Asp Pro Ser Thr Ile Glu Lys 115 120 125 Leu Ala Lys Asn Lys Gln Lys Pro Ile Thr Pro Glu Thr Ala Glu Lys 130 135 140 Leu Ala Arg Asp Leu Lys Ala Val Lys Tyr Val Glu Cys Ser Ala Leu 145 150 155 160 Thr Gln Lys Gly Leu Lys Asn Val Phe Asp Glu Ala Ile Leu Ala Ala 165 170 175 Leu Glu Pro Pro Glu Pro Lys Lys Ser Arg Arg Cys Val Leu Leu 180 185 190 <210> 65 <211> 1663 <212> PRT <213> Homo sapiens <400> 65 Met Gly Pro Thr Ser Gly Pro Ser Leu Leu Leu Leu Leu Leu Thr His 1 5 10 15 Leu Pro Leu Ala Leu Gly Ser Pro Met Tyr Ser Ile Ile Thr Pro Asn 20 25 30 Ile Leu Arg Leu Glu Ser Glu Glu Thr Met Val Leu Glu Ala His Asp 35 40 45 Ala Gln Gly Asp Val Pro Val Thr Val Thr Val His Asp Phe Pro Gly 50 55 60 Lys Lys Leu Val Leu Ser Ser Glu Lys Thr Val Leu Thr Pro Ala Thr 65 70 75 80 Asn His Met Gly Asn Val Thr Phe Thr Ile Pro Ala Asn Arg Glu Phe 85 90 95 Lys Ser Glu Lys Gly Arg Asn Lys Phe Val Thr Val Gln Ala Thr Phe 100 105 110 Gly Thr Gln Val Val Glu Lys Val Val Leu Val Ser Leu Gln Ser Gly 115 120 125 Tyr Leu Phe Ile Gln Thr Asp Lys Thr Ile Tyr Thr Pro Gly Ser Thr 130 135 140 Val Leu Tyr Arg Ile Phe Thr Val Asn His Lys Leu Leu Pro Val Gly 145 150 155 160 Arg Thr Val Met Val Asn Ile Glu Asn Pro Glu Gly Ile Pro Val Lys 165 170 175 Gln Asp Ser Leu Ser Ser Gln Asn Gln Leu Gly Val Leu Pro Leu Ser 180 185 190 Trp Asp Ile Pro Glu Leu Val Asn Met Gly Gln Trp Lys Ile Arg Ala 195 200 205 Tyr Tyr Glu Asn Ser Pro Gln Gln Val Phe Ser Thr Glu Phe Glu Val 210 215 220 Lys Glu Tyr Val Leu Pro Ser Phe Glu Val Ile Val Glu Pro Thr Glu 225 230 235 240 Lys Phe Tyr Tyr Ile Tyr Asn Glu Lys Gly Leu Glu Val Thr Ile Thr 245 250 255 Ala Arg Phe Leu Tyr Gly Lys Lys Val Glu Gly Thr Ala Phe Val Ile 260 265 270 Phe Gly Ile Gln Asp Gly Glu Gln Arg Ile Ser Leu Pro Glu Ser Leu 275 280 285 Lys Arg Ile Pro Ile Glu Asp Gly Ser Gly Glu Val Val Leu Ser Arg 290 295 300 Lys Val Leu Leu Asp Gly Val Gln Asn Pro Arg Ala Glu Asp Leu Val 305 310 315 320 Gly Lys Ser Leu Tyr Val Ser Ala Thr Val Ile Leu His Ser Gly Ser 325 330 335 Asp Met Val Gln Ala Glu Arg Ser Gly Ile Pro Ile Val Thr Ser Pro 340 345 350 Tyr Gln Ile His Phe Thr Lys Thr Pro Lys Tyr Phe Lys Pro Gly Met 355 360 365 Pro Phe Asp Leu Met Val Phe Val Thr Asn Pro Asp Gly Ser Pro Ala 370 375 380 Tyr Arg Val Pro Val Ala Val Gln Gly Glu Asp Thr Val Gln Ser Leu 385 390 395 400 Thr Gln Gly Asp Gly Val Ala Lys Leu Ser Ile Asn Thr His Pro Ser 405 410 415 Gln Lys Pro Leu Ser Ile Thr Val Arg Thr Lys Lys Gln Glu Leu Ser 420 425 430 Glu Ala Glu Gln Ala Thr Arg Thr Met Gln Ala Leu Pro Tyr Ser Thr 435 440 445 Val Gly Asn Ser Asn Asn Tyr Leu His Leu Ser Val Leu Arg Thr Glu 450 455 460 Leu Arg Pro Gly Glu Thr Leu Asn Val Asn Phe Leu Leu Arg Met Asp 465 470 475 480 Arg Ala His Glu Ala Lys Ile Arg Tyr Tyr Thr Tyr Leu Ile Met Asn 485 490 495 Lys Gly Arg Leu Leu Lys Ala Gly Arg Gln Val Arg Glu Pro Gly Gln 500 505 510 Asp Leu Val Val Leu Pro Leu Ser Ile Thr Thr Asp Phe Ile Pro Ser 515 520 525 Phe Arg Leu Val Ala Tyr Tyr Thr Leu Ile Gly Ala Ser Gly Gln Arg 530 535 540 Glu Val Val Ala Asp Ser Val Trp Val Asp Val Lys Asp Ser Cys Val 545 550 555 560 Gly Ser Leu Val Val Lys Ser Gly Gln Ser Glu Asp Arg Gln Pro Val 565 570 575 Pro Gly Gln Gln Met Thr Leu Lys Ile Glu Gly Asp His Gly Ala Arg 580 585 590 Val Val Leu Val Ala Val Asp Lys Gly Val Phe Val Leu Asn Lys Lys 595 600 605 Asn Lys Leu Thr Gln Ser Lys Ile Trp Asp Val Val Glu Lys Ala Asp 610 615 620 Ile Gly Cys Thr Pro Gly Ser Gly Lys Asp Tyr Ala Gly Val Phe Ser 625 630 635 640 Asp Ala Gly Leu Thr Phe Thr Ser Ser Ser Gly Gln Gln Thr Ala Gln 645 650 655 Arg Ala Glu Leu Gln Cys Pro Gln Pro Ala Ala Arg Arg Arg Arg Ser 660 665 670 Val Gln Leu Thr Glu Lys Arg Met Asp Lys Val Gly Lys Tyr Pro Lys 675 680 685 Glu Leu Arg Lys Cys Cys Glu Asp Gly Met Arg Glu Asn Pro Met Arg 690 695 700 Phe Ser Cys Gln Arg Arg Thr Arg Phe Ile Ser Leu Gly Glu Ala Cys 705 710 715 720 Lys Lys Val Phe Leu Asp Cys Cys Asn Tyr Ile Thr Glu Leu Arg Arg 725 730 735 Gln His Ala Arg Ala Ser His Leu Gly Leu Ala Arg Ser Asn Leu Asp 740 745 750 Glu Asp Ile Ile Ala Glu Glu Asn Ile Val Ser Arg Ser Glu Phe Pro 755 760 765 Glu Ser Trp Leu Trp Asn Val Glu Asp Leu Lys Glu Pro Pro Lys Asn 770 775 780 Gly Ile Ser Thr Lys Leu Met Asn Ile Phe Leu Lys Asp Ser Ile Thr 785 790 795 800 Thr Trp Glu Ile Leu Ala Val Ser Met Ser Asp Lys Lys Gly Ile Cys 805 810 815 Val Ala Asp Pro Phe Glu Val Thr Val Met Gln Asp Phe Phe Ile Asp 820 825 830 Leu Arg Leu Pro Tyr Ser Val Val Arg Asn Glu Gln Val Glu Ile Arg 835 840 845 Ala Val Leu Tyr Asn Tyr Arg Gln Asn Gln Glu Leu Lys Val Arg Val 850 855 860 Glu Leu Leu His Asn Pro Ala Phe Cys Ser Leu Ala Thr Thr Lys Arg 865 870 875 880 Arg His Gln Gln Thr Val Thr Ile Pro Pro Lys Ser Ser Leu Ser Val 885 890 895 Pro Tyr Val Ile Val Pro Leu Lys Thr Gly Leu Gln Glu Val Glu Val 900 905 910 Lys Ala Ala Val Tyr His His Phe Ile Ser Asp Gly Val Arg Lys Ser 915 920 925 Leu Lys Val Val Pro Glu Gly Ile Arg Met Asn Lys Thr Val Ala Val 930 935 940 Arg Thr Leu Asp Pro Glu Arg Leu Gly Arg Glu Gly Val Gln Lys Glu 945 950 955 960 Asp Ile Pro Pro Ala Asp Leu Ser Asp Gln Val Pro Asp Thr Glu Ser 965 970 975 Glu Thr Arg Ile Leu Leu Gln Gly Thr Pro Val Ala Gln Met Thr Glu 980 985 990 Asp Ala Val Asp Ala Glu Arg Leu Lys His Leu Ile Val Thr Pro Ser 995 1000 1005 Gly Cys Gly Glu Gln Asn Met Ile Gly Met Thr Pro Thr Val Ile 1010 1015 1020 Ala Val His Tyr Leu Asp Glu Thr Glu Gln Trp Glu Lys Phe Gly 1025 1030 1035 Leu Glu Lys Arg Gln Gly Ala Leu Glu Leu Ile Lys Lys Gly Tyr 1040 1045 1050 Thr Gln Gln Leu Ala Phe Arg Gln Pro Ser Ser Ala Phe Ala Ala 1055 1060 1065 Phe Val Lys Arg Ala Pro Ser Thr Trp Leu Thr Ala Tyr Val Val 1070 1075 1080 Lys Val Phe Ser Leu Ala Val Asn Leu Ile Ala Ile Asp Ser Gln 1085 1090 1095 Val Leu Cys Gly Ala Val Lys Trp Leu Ile Leu Glu Lys Gln Lys 1100 1105 1110 Pro Asp Gly Val Phe Gln Glu Asp Ala Pro Val Ile His Gln Glu 1115 1120 1125 Met Ile Gly Gly Leu Arg Asn Asn Asn Glu Lys Asp Met Ala Leu 1130 1135 1140 Thr Ala Phe Val Leu Ile Ser Leu Gln Glu Ala Lys Asp Ile Cys 1145 1150 1155 Glu Glu Gln Val Asn Ser Leu Pro Gly Ser Ile Thr Lys Ala Gly 1160 1165 1170 Asp Phe Leu Glu Ala Asn Tyr Met Asn Leu Gln Arg Ser Tyr Thr 1175 1180 1185 Val Ala Ile Ala Gly Tyr Ala Leu Ala Gln Met Gly Arg Leu Lys 1190 1195 1200 Gly Pro Leu Leu Asn Lys Phe Leu Thr Thr Ala Lys Asp Lys Asn 1205 1210 1215 Arg Trp Glu Asp Pro Gly Lys Gln Leu Tyr Asn Val Glu Ala Thr 1220 1225 1230 Ser Tyr Ala Leu Leu Ala Leu Leu Gln Leu Lys Asp Phe Asp Phe 1235 1240 1245 Val Pro Pro Val Val Arg Trp Leu Asn Glu Gln Arg Tyr Tyr Gly 1250 1255 1260 Gly Gly Tyr Gly Ser Thr Gln Ala Thr Phe Met Val Phe Gln Ala 1265 1270 1275 Leu Ala Gln Tyr Gln Lys Asp Ala Pro Asp His Gln Glu Leu Asn 1280 1285 1290 Leu Asp Val Ser Leu Gln Leu Pro Ser Arg Ser Ser Lys Ile Thr 1295 1300 1305 His Arg Ile His Trp Glu Ser Ala Ser Leu Leu Arg Ser Glu Glu 1310 1315 1320 Thr Lys Glu Asn Glu Gly Phe Thr Val Thr Ala Glu Gly Lys Gly 1325 1330 1335 Gln Gly Thr Leu Ser Val Val Thr Met Tyr His Ala Lys Ala Lys 1340 1345 1350 Asp Gln Leu Thr Cys Asn Lys Phe Asp Leu Lys Val Thr Ile Lys 1355 1360 1365 Pro Ala Pro Glu Thr Glu Lys Arg Pro Gln Asp Ala Lys Asn Thr 1370 1375 1380 Met Ile Leu Glu Ile Cys Thr Arg Tyr Arg Gly Asp Gln Asp Ala 1385 1390 1395 Thr Met Ser Ile Leu Asp Ile Ser Met Met Thr Gly Phe Ala Pro 1400 1405 1410 Asp Thr Asp Asp Leu Lys Gln Leu Ala Asn Gly Val Asp Arg Tyr 1415 1420 1425 Ile Ser Lys Tyr Glu Leu Asp Lys Ala Phe Ser Asp Arg Asn Thr 1430 1435 1440 Leu Ile Ile Tyr Leu Asp Lys Val Ser His Ser Glu Asp Asp Cys 1445 1450 1455 Leu Ala Phe Lys Val His Gln Tyr Phe Asn Val Glu Leu Ile Gln 1460 1465 1470 Pro Gly Ala Val Lys Val Tyr Ala Tyr Tyr Asn Leu Glu Glu Ser 1475 1480 1485 Cys Thr Arg Phe Tyr His Pro Glu Lys Glu Asp Gly Lys Leu Asn 1490 1495 1500 Lys Leu Cys Arg Asp Glu Leu Cys Arg Cys Ala Glu Glu Asn Cys 1505 1510 1515 Phe Ile Gln Lys Ser Asp Asp Lys Val Thr Leu Glu Glu Arg Leu 1520 1525 1530 Asp Lys Ala Cys Glu Pro Gly Val Asp Tyr Val Tyr Lys Thr Arg 1535 1540 1545 Leu Val Lys Val Gln Leu Ser Asn Asp Phe Asp Glu Tyr Ile Met 1550 1555 1560 Ala Ile Glu Gln Thr Ile Lys Ser Gly Ser Asp Glu Val Gln Val 1565 1570 1575 Gly Gln Gln Arg Thr Phe Ile Ser Pro Ile Lys Cys Arg Glu Ala 1580 1585 1590 Leu Lys Leu Glu Glu Lys Lys His Tyr Leu Met Trp Gly Leu Ser 1595 1600 1605 Ser Asp Phe Trp Gly Glu Lys Pro Asn Leu Ser Tyr Ile Ile Gly 1610 1615 1620 Lys Asp Thr Trp Val Glu His Trp Pro Glu Glu Asp Glu Cys Gln 1625 1630 1635 Asp Glu Glu Asn Gln Lys Gln Cys Gln Asp Leu Gly Ala Phe Thr 1640 1645 1650 Glu Ser Met Val Val Phe Gly Cys Pro Asn 1655 1660 <210> 66 <211> 461 <212> PRT <213> Homo sapiens <400> 66 Met Ser Arg Gln Val Val Arg Ser Ser Lys Phe Arg His Val Phe Gly 1 5 10 15 Gln Pro Ala Lys Ala Asp Gln Cys Tyr Glu Asp Val Arg Val Ser Gln 20 25 30 Thr Thr Trp Asp Ser Gly Phe Cys Ala Val Asn Pro Lys Phe Val Ala 35 40 45 Leu Ile Cys Glu Ala Ser Gly Gly Gly Ala Phe Leu Val Leu Pro Leu 50 55 60 Gly Lys Thr Gly Arg Val Asp Lys Asn Ala Pro Thr Val Cys Gly His 65 70 75 80 Thr Ala Pro Val Leu Asp Ile Ala Trp Cys Pro His Asn Asp Asn Val 85 90 95 Ile Ala Ser Gly Ser Glu Asp Cys Thr Val Met Val Trp Glu Ile Pro 100 105 110 Asp Gly Gly Leu Met Leu Pro Leu Arg Glu Pro Val Val Thr Leu Glu 115 120 125 Gly His Thr Lys Arg Val Gly Ile Val Ala Trp His Thr Thr Ala Gln 130 135 140 Asn Val Leu Leu Ser Ala Gly Cys Asp Asn Val Ile Met Val Trp Asp 145 150 155 160 Val Gly Thr Gly Ala Ala Met Leu Thr Leu Gly Pro Glu Val His Pro 165 170 175 Asp Thr Ile Tyr Ser Val Asp Trp Ser Arg Asp Gly Gly Leu Ile Cys 180 185 190 Thr Ser Cys Arg Asp Lys Arg Val Arg Ile Ile Glu Pro Arg Lys Gly 195 200 205 Thr Val Val Ala Glu Lys Asp Arg Pro His Glu Gly Thr Arg Pro Val 210 215 220 Arg Ala Val Phe Val Ser Glu Gly Lys Ile Leu Thr Thr Gly Phe Ser 225 230 235 240 Arg Met Ser Glu Arg Gln Val Ala Leu Trp Asp Thr Lys His Leu Glu 245 250 255 Glu Pro Leu Ser Leu Gln Glu Leu Asp Thr Ser Ser Gly Val Leu Leu 260 265 270 Pro Phe Phe Asp Pro Asp Thr Asn Ile Val Tyr Leu Cys Gly Lys Gly 275 280 285 Asp Ser Ser Ile Arg Tyr Phe Glu Ile Thr Ser Glu Ala Pro Phe Leu 290 295 300 His Tyr Leu Ser Met Phe Ser Ser Lys Glu Ser Gln Arg Gly Met Gly 305 310 315 320 Tyr Met Pro Lys Arg Gly Leu Glu Val Asn Lys Cys Glu Ile Ala Arg 325 330 335 Phe Tyr Lys Leu His Glu Arg Arg Cys Glu Pro Ile Ala Met Thr Val 340 345 350 Pro Arg Lys Ser Asp Leu Phe Gln Glu Asp Leu Tyr Pro Pro Thr Ala 355 360 365 Gly Pro Asp Pro Ala Leu Thr Ala Glu Glu Trp Leu Gly Gly Arg Asp 370 375 380 Ala Gly Pro Leu Leu Ile Ser Leu Lys Asp Gly Tyr Val Pro Pro Lys 385 390 395 400 Ser Arg Glu Leu Arg Val Asn Arg Gly Leu Asp Thr Gly Arg Arg Arg 405 410 415 Ala Ala Pro Glu Ala Ser Gly Thr Pro Ser Ser Asp Ala Val Ser Arg 420 425 430 Leu Glu Glu Glu Met Arg Lys Leu Gln Ala Thr Val Gln Glu Leu Gln 435 440 445 Lys Arg Leu Asp Arg Leu Glu Glu Thr Val Gln Ala Lys 450 455 460 <210> 67 <211> 868 <212> PRT <213> Homo sapiens <400> 67 Met Ala Thr Phe Ile Ser Val Gln Leu Lys Lys Thr Ser Glu Val Asp 1 5 10 15 Leu Ala Lys Pro Leu Val Lys Phe Ile Gln Gln Thr Tyr Pro Ser Gly 20 25 30 Gly Glu Glu Gln Ala Gln Tyr Cys Arg Ala Ala Glu Glu Leu Ser Lys 35 40 45 Leu Arg Arg Ala Ala Val Gly Arg Pro Leu Asp Lys His Glu Gly Ala 50 55 60 Leu Glu Thr Leu Leu Arg Tyr Tyr Asp Gln Ile Cys Ser Ile Glu Pro 65 70 75 80 Lys Phe Pro Phe Ser Glu Asn Gln Ile Cys Leu Thr Phe Thr Trp Lys 85 90 95 Asp Ala Phe Asp Lys Gly Ser Leu Phe Gly Gly Ser Val Lys Leu Ala 100 105 110 Leu Ala Ser Leu Gly Tyr Glu Lys Ser Cys Val Leu Phe Asn Cys Ala 115 120 125 Ala Leu Ala Ser Gln Ile Ala Ala Glu Gln Asn Leu Asp Asn Asp Glu 130 135 140 Gly Leu Lys Ile Ala Ala Lys His Tyr Gln Phe Ala Ser Gly Ala Phe 145 150 155 160 Leu His Ile Lys Glu Thr Val Leu Ser Ala Leu Ser Arg Glu Pro Thr 165 170 175 Val Asp Ile Ser Pro Asp Thr Val Gly Thr Leu Ser Leu Ile Met Leu 180 185 190 Ala Gln Ala Gln Glu Val Phe Phe Leu Lys Ala Thr Arg Asp Lys Met 195 200 205 Lys Asp Ala Ile Ile Ala Lys Leu Ala Asn Gln Ala Ala Asp Tyr Phe 210 215 220 Gly Asp Ala Phe Lys Gln Cys Gln Tyr Lys Asp Thr Leu Pro Lys Glu 225 230 235 240 Val Phe Pro Val Leu Ala Ala Lys His Cys Ile Met Gln Ala Asn Ala 245 250 255 Glu Tyr His Gln Ser Ile Leu Ala Lys Gln Gln Lys Lys Phe Gly Glu 260 265 270 Glu Ile Ala Arg Leu Gln His Ala Ala Glu Leu Ile Lys Thr Val Ala 275 280 285 Ser Arg Tyr Asp Glu Tyr Val Asn Val Lys Asp Phe Ser Asp Lys Ile 290 295 300 Asn Arg Ala Leu Ala Ala Ala Lys Lys Asp Asn Asp Phe Ile Tyr His 305 310 315 320 Asp Arg Val Pro Asp Leu Lys Asp Leu Asp Pro Ile Gly Lys Ala Thr 325 330 335 Leu Val Lys Ser Thr Pro Val Asn Val Pro Ile Ser Gln Lys Phe Thr 340 345 350 Asp Leu Phe Glu Lys Met Val Pro Val Ser Val Gln Gln Ser Leu Ala 355 360 365 Ala Tyr Asn Gln Arg Lys Ala Asp Leu Val Asn Arg Ser Ile Ala Gln 370 375 380 Met Arg Glu Ala Thr Thr Leu Ala Asn Gly Val Leu Ala Ser Leu Asn 385 390 395 400 Leu Pro Ala Ala Ile Glu Asp Val Ser Gly Asp Thr Val Pro Gln Ser 405 410 415 Ile Leu Thr Lys Ser Arg Ser Val Ile Glu Gln Gly Gly Ile Gln Thr 420 425 430 Val Asp Gln Leu Ile Lys Glu Leu Pro Glu Leu Leu Gln Arg Asn Arg 435 440 445 Glu Ile Leu Asp Glu Ser Leu Arg Leu Leu Asp Glu Glu Glu Ala Thr 450 455 460 Asp Asn Asp Leu Arg Ala Lys Phe Lys Glu Arg Trp Gln Arg Thr Pro 465 470 475 480 Ser Asn Glu Leu Tyr Lys Pro Leu Arg Ala Glu Gly Thr Asn Phe Arg 485 490 495 Thr Val Leu Asp Lys Ala Val Gln Ala Asp Gly Gln Val Lys Glu Cys 500 505 510 Tyr Gln Ser His Arg Asp Thr Ile Val Leu Leu Cys Lys Pro Glu Pro 515 520 525 Glu Leu Asn Ala Ala Ile Pro Ser Ala Asn Pro Ala Lys Thr Met Gln 530 535 540 Gly Ser Glu Val Val Asn Val Leu Lys Ser Leu Leu Ser Asn Leu Asp 545 550 555 560 Glu Val Lys Lys Glu Arg Glu Gly Leu Glu Asn Asp Leu Lys Ser Val 565 570 575 Asn Phe Asp Met Thr Ser Lys Phe Leu Thr Ala Leu Ala Gln Asp Gly 580 585 590 Val Ile Asn Glu Glu Ala Leu Ser Val Thr Glu Leu Asp Arg Val Tyr 595 600 605 Gly Gly Leu Thr Thr Lys Val Gln Glu Ser Leu Lys Lys Gln Glu Gly 610 615 620 Leu Leu Lys Asn Ile Gln Val Ser His Gln Glu Phe Ser Lys Met Lys 625 630 635 640 Gln Ser Asn Asn Glu Ala Asn Leu Arg Glu Glu Val Leu Lys Asn Leu 645 650 655 Ala Thr Ala Tyr Asp Asn Phe Val Glu Leu Val Ala Asn Leu Lys Glu 660 665 670 Gly Thr Lys Phe Tyr Asn Glu Leu Thr Glu Ile Leu Val Arg Phe Gln 675 680 685 Asn Lys Cys Ser Asp Ile Val Phe Ala Arg Lys Thr Glu Arg Asp Glu 690 695 700 Leu Leu Lys Asp Leu Gln Gln Ser Ile Ala Arg Glu Pro Ser Ala Pro 705 710 715 720 Ser Ile Pro Thr Pro Ala Tyr Gln Ser Ser Pro Ala Gly Gly His Ala 725 730 735 Pro Thr Pro Pro Thr Pro Ala Pro Arg Thr Met Pro Pro Thr Lys Pro 740 745 750 Gln Pro Pro Ala Arg Pro Pro Pro Pro Val Leu Pro Ala Asn Arg Ala 755 760 765 Pro Ser Ala Thr Ala Pro Ser Pro Val Gly Ala Gly Thr Ala Ala Pro 770 775 780 Ala Pro Ser Gln Thr Pro Gly Ser Ala Pro Pro Pro Gln Ala Gln Gly 785 790 795 800 Pro Pro Tyr Pro Thr Tyr Pro Gly Tyr Pro Gly Tyr Cys Gln Met Pro 805 810 815 Met Pro Met Gly Tyr Asn Pro Tyr Ala Tyr Gly Gln Tyr Asn Met Pro 820 825 830 Tyr Pro Pro Val Tyr His Gln Ser Pro Gly Gln Ala Pro Tyr Pro Gly 835 840 845 Pro Gln Gln Pro Ser Tyr Pro Phe Pro Gln Pro Pro Gln Gln Ser Tyr 850 855 860 Tyr Pro Gln Gln 865 <210> 68 <211> 94 <212> PRT <213> Homo sapiens <400> 68 Met Arg Thr Leu Ala Ile Leu Ala Ala Ile Leu Leu Val Ala Leu Gln 1 5 10 15 Ala Gln Ala Glu Pro Leu Gln Ala Arg Ala Asp Glu Val Ala Ala Ala 20 25 30 Pro Glu Gln Ile Ala Ala Asp Ile Pro Glu Val Val Val Ser Leu Ala 35 40 45 Trp Asp Glu Ser Leu Ala Pro Lys His Pro Gly Ser Arg Lys Asn Met 50 55 60 Ala Cys Tyr Cys Arg Ile Pro Ala Cys Ile Ala Gly Glu Arg Arg Tyr 65 70 75 80 Gly Thr Cys Ile Tyr Gln Gly Arg Leu Trp Ala Phe Cys Cys 85 90 <210> 69 <211> 275 <212> PRT <213> Homo sapiens <400> 69 Met Glu Glu Val Arg Glu Gly His Ala Leu Gly Gly Gly Met Glu Ala 1 5 10 15 Asp Gly Pro Ala Ser Leu Gln Glu Leu Pro Pro Ser Pro Arg Ser Pro 20 25 30 Ser Pro Pro Pro Ser Pro Pro Pro Leu Pro Ser Pro Pro Ser Leu Pro 35 40 45 Ser Pro Ala Ala Pro Glu Ala Pro Glu Leu Pro Glu Pro Ala Gln Pro 50 55 60 Ser Glu Ala His Ala Arg Gln Leu Leu Leu Glu Glu Trp Gly Pro Leu 65 70 75 80 Ser Gly Gly Leu Glu Leu Pro Gln Arg Leu Thr Trp Lys Leu Leu Leu 85 90 95 Leu Arg Arg Pro Leu Tyr Arg Asn Leu Leu Arg Ser Pro Asn Pro Glu 100 105 110 Gly Ile Asn Ile Tyr Glu Pro Ala Pro Pro Thr Gly Pro Thr Gln Arg 115 120 125 Pro Leu Glu Thr Leu Gly Asn Phe Arg Gly Trp Tyr Ile Arg Thr Glu 130 135 140 Lys Leu Gln Gln Asn Gln Ser Trp Thr Val Lys Gln Gln Cys Val Asp 145 150 155 160 Leu Leu Ala Glu Gly Leu Trp Glu Glu Leu Leu Asp Asp Glu Gln Pro 165 170 175 Ala Ile Thr Val Met Asp Trp Phe Glu Asp Ser Arg Leu Asp Ala Cys 180 185 190 Val Tyr Glu Leu His Val Trp Leu Leu Ala Ala Asp Arg Arg Thr Val 195 200 205 Ile Ala Gln His His Val Ala Pro Arg Thr Ser Gly Arg Gly Pro Pro 210 215 220 Gly Arg Trp Val Gln Val Ser His Val Phe Arg His Tyr Gly Pro Gly 225 230 235 240 Val Arg Phe Ile His Phe Leu His Lys Ala Lys Asn Arg Met Glu Pro 245 250 255 Gly Gly Leu Arg Arg Thr Arg Val Thr Asp Ser Ser Val Ser Val Gln 260 265 270 Leu Arg Glu 275 <210> 70 <211> 188 <212> PRT <213> Homo sapiens <400> 70 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> 71 <211> 522 <212> PRT <213> Homo sapiens <400> 71 Met Ala Leu Leu Pro Arg Ala Leu Ser Ala Gly Ala Gly Pro Ser Trp 1 5 10 15 Arg Arg Ala Ala Arg Ala Phe Arg Gly Phe Leu Leu Leu Leu Pro Glu 20 25 30 Pro Ala Ala Leu Thr Arg Ala Leu Ser Arg Ala Met Ala Cys Arg Gln 35 40 45 Glu Pro Gln Pro Gln Gly Pro Pro Pro Ala Ala Gly Ala Val Ala Ser 50 55 60 Tyr Asp Tyr Leu Val Ile Gly Gly Gly Ser Gly Gly Leu Ala Ser Ala 65 70 75 80 Arg Arg Ala Ala Glu Leu Gly Ala Arg Ala Ala Val Val Glu Ser His 85 90 95 Lys Leu Gly Gly Thr Cys Val Asn Val Gly Cys Val Pro Lys Lys Val 100 105 110 Met Trp Asn Thr Ala Val His Ser Glu Phe Met His Asp His Ala Asp 115 120 125 Tyr Gly Phe Pro Ser Cys Glu Gly Lys Phe Asn Trp Arg Val Ile Lys 130 135 140 Glu Lys Arg Asp Ala Tyr Val Ser Arg Leu Asn Ala Ile Tyr Gln Asn 145 150 155 160 Asn Leu Thr Lys Ser His Ile Glu Ile Ile Arg Gly His Ala Ala Phe 165 170 175 Thr Ser Asp Pro Lys Pro Thr Ile Glu Val Ser Gly Lys Lys Tyr Thr 180 185 190 Ala Pro His Ile Leu Ile Ala Thr Gly Gly Met Pro Ser Thr Pro His 195 200 205 Glu Ser Gln Ile Pro Gly Ala Ser Leu Gly Ile Thr Ser Asp Gly Phe 210 215 220 Phe Gln Leu Glu Glu Leu Pro Gly Arg Ser Val Ile Val Gly Ala Gly 225 230 235 240 Tyr Ile Ala Val Glu Met Ala Gly Ile Leu Ser Ala Leu Gly Ser Lys 245 250 255 Thr Ser Leu Met Ile Arg His Asp Lys Val Leu Arg Ser Phe Asp Ser 260 265 270 Met Ile Ser Thr Asn Cys Thr Glu Glu Leu Glu Asn Ala Gly Val Glu 275 280 285 Val Leu Lys Phe Ser Gln Val Lys Glu Val Lys Lys Thr Leu Ser Gly 290 295 300 Leu Glu Val Ser Met Val Thr Ala Val Pro Gly Arg Leu Pro Val Met 305 310 315 320 Thr Met Ile Pro Asp Val Asp Cys Leu Leu Trp Ala Ile Gly Arg Val 325 330 335 Pro Asn Thr Lys Asp Leu Ser Leu Asn Lys Leu Gly Ile Gln Thr Asp 340 345 350 Asp Lys Gly His Ile Ile Val Asp Glu Phe Gln Asn Thr Asn Val Lys 355 360 365 Gly Ile Tyr Ala Val Gly Asp Val Cys Gly Lys Ala Leu Leu Thr Pro 370 375 380 Val Ala Ile Ala Ala Gly Arg Lys Leu Ala His Arg Leu Phe Glu Tyr 385 390 395 400 Lys Glu Asp Ser Lys Leu Asp Tyr Asn Asn Ile Pro Thr Val Val Phe 405 410 415 Ser His Pro Pro Ile Gly Thr Val Gly Leu Thr Glu Asp Glu Ala Ile 420 425 430 His Lys Tyr Gly Ile Glu Asn Val Lys Thr Tyr Ser Thr Ser Phe Thr 435 440 445 Pro Met Tyr His Ala Val Thr Lys Arg Lys Thr Lys Cys Val Met Lys 450 455 460 Met Val Cys Ala Asn Lys Glu Glu Lys Val Val Gly Ile His Met Gln 465 470 475 480 Gly Leu Gly Cys Asp Glu Met Leu Gln Gly Phe Ala Val Ala Val Lys 485 490 495 Met Gly Ala Thr Lys Ala Asp Phe Asp Asn Thr Val Ala Ile His Pro 500 505 510 Thr Ser Ser Glu Glu Leu Val Thr Leu Arg 515 520 <210> 72 <211> 644 <212> PRT <213> Homo sapiens <400> 72 Met Ser Arg Gln Phe Ser Ser Arg Ser Gly Tyr Arg Ser Gly Gly Gly 1 5 10 15 Phe Ser Ser Gly Ser Ala Gly Ile Ile Asn Tyr Gln Arg Arg Thr Thr 20 25 30 Ser Ser Ser Thr Arg Arg Ser Gly Gly Gly Gly Gly Arg Phe Ser Ser 35 40 45 Cys Gly Gly Gly Gly Gly Ser Phe Gly Ala Gly Gly Gly Phe Gly Ser 50 55 60 Arg Ser Leu Val Asn Leu Gly Gly Ser Lys Ser Ile Ser Ile Ser Val 65 70 75 80 Ala Arg Gly Gly Gly Arg Gly Ser Gly Phe Gly Gly Gly Tyr Gly Gly 85 90 95 Gly Gly Phe Gly Gly Gly Gly Phe Gly Gly Gly Gly Phe Gly Gly Gly 100 105 110 Gly Ile Gly Gly Gly Gly Phe Gly Gly Phe Gly Ser Gly Gly Gly Gly 115 120 125 Phe Gly Gly Gly Gly Phe Gly Gly Gly Gly Tyr Gly Gly Gly Tyr Gly 130 135 140 Pro Val Cys Pro Pro Gly Gly Ile Gln Glu Val Thr Ile Asn Gln Ser 145 150 155 160 Leu Leu Gln Pro Leu Asn Val Glu Ile Asp Pro Glu Ile Gln Lys Val 165 170 175 Lys Ser Arg Glu Arg Glu Gln Ile Lys Ser Leu Asn Asn Gln Phe Ala 180 185 190 Ser Phe Ile Asp Lys Val Arg Phe Leu Glu Gln Gln Asn Gln Val Leu 195 200 205 Gln Thr Lys Trp Glu Leu Leu Gln Gln Val Asp Thr Ser Thr Arg Thr 210 215 220 His Asn Leu Glu Pro Tyr Phe Glu Ser Phe Ile Asn Asn Leu Arg Arg 225 230 235 240 Arg Val Asp Gln Leu Lys Ser Asp Gln Ser Arg Leu Asp Ser Glu Leu 245 250 255 Lys Asn Met Gln Asp Met Val Glu Asp Tyr Arg Asn Lys Tyr Glu Asp 260 265 270 Glu Ile Asn Lys Arg Thr Asn Ala Glu Asn Glu Phe Val Thr Ile Lys 275 280 285 Lys Asp Val Asp Gly Ala Tyr Met Thr Lys Val Asp Leu Gln Ala Lys 290 295 300 Leu Asp Asn Leu Gln Gln Glu Ile Asp Phe Leu Thr Ala Leu Tyr Gln 305 310 315 320 Ala Glu Leu Ser Gln Met Gln Thr Gln Ile Ser Glu Thr Asn Val Ile 325 330 335 Leu Ser Met Asp Asn Asn Arg Ser Leu Asp Leu Asp Ser Ile Ile Ala 340 345 350 Glu Val Lys Ala Gln Tyr Glu Asp Ile Ala Gln Lys Ser Lys Ala Glu 355 360 365 Ala Glu Ser Leu Tyr Gln Ser Lys Tyr Glu Glu Leu Gln Ile Thr Ala 370 375 380 Gly Arg His Gly Asp Ser Val Arg Asn Ser Lys Ile Glu Ile Ser Glu 385 390 395 400 Leu Asn Arg Val Ile Gln Arg Leu Arg Ser Glu Ile Asp Asn Val Lys 405 410 415 Lys Gln Ile Ser Asn Leu Gln Gln Ser Ile Ser Asp Ala Glu Gln Arg 420 425 430 Gly Glu Asn Ala Leu Lys Asp Ala Lys Asn Lys Leu Asn Asp Leu Glu 435 440 445 Asp Ala Leu Gln Gln Ala Lys Glu Asp Leu Ala Arg Leu Leu Arg Asp 450 455 460 Tyr Gln Glu Leu Met Asn Thr Lys Leu Ala Leu Asp Leu Glu Ile Ala 465 470 475 480 Thr Tyr Arg Thr Leu Leu Glu Gly Glu Glu Ser Arg Met Ser Gly Glu 485 490 495 Cys Ala Pro Asn Val Ser Val Ser Val Ser Thr Ser His Thr Thr Ile 500 505 510 Ser Gly Gly Gly Ser Arg Gly Gly Gly Gly Gly Gly Tyr Gly Ser Gly 515 520 525 Gly Ser Ser Tyr Gly Ser Gly Gly Gly Ser Tyr Gly Ser Gly Gly Gly 530 535 540 Gly Gly Gly Gly Arg Gly Ser Tyr Gly Ser Gly Gly Ser Ser Tyr Gly 545 550 555 560 Ser Gly Gly Gly Ser Tyr Gly Ser Gly Gly Gly Gly Gly Gly His Gly 565 570 575 Ser Tyr Gly Ser Gly Ser Ser Ser Gly Gly Tyr Arg Gly Gly Ser Gly 580 585 590 Gly Gly Gly Gly Gly Ser Ser Gly Gly Arg Gly Ser Gly Gly Gly Ser 595 600 605 Ser Gly Gly Ser Ile Gly Gly Arg Gly Ser Ser Ser Gly Gly Val Lys 610 615 620 Ser Ser Gly Gly Ser Ser Ser Val Lys Phe Val Ser Thr Thr Tyr Ser 625 630 635 640 Gly Val Thr Arg <210> 73 <211> 196 <212> PRT <213> Homo sapiens <400> 73 Met Lys Pro Leu Val Val Phe Val Leu Gly Gly Pro Gly Ala Gly Lys 1 5 10 15 Gly Thr Gln Cys Ala Arg Ile Val Glu Lys Tyr Gly Tyr Thr His Leu 20 25 30 Ser Ala Gly Glu Leu Leu Arg Asp Glu Arg Lys Asn Pro Asp Ser Gln 35 40 45 Tyr Gly Glu Leu Ile Glu Lys Tyr Ile Lys Glu Gly Lys Ile Val Pro 50 55 60 Val Glu Ile Thr Ile Ser Leu Leu Lys Arg Glu Met Asp Gln Thr Met 65 70 75 80 Ala Ala Asn Ala Gln Lys Asn Lys Phe Leu Ile Asp Gly Phe Pro Arg 85 90 95 Asn Gln Asp Asn Leu Gln Gly Trp Asn Lys Thr Met Asp Gly Lys Ala 100 105 110 Asp Val Ser Phe Val Leu Phe Phe Asp Cys Asn Asn Glu Ile Cys Ile 115 120 125 Glu Arg Cys Leu Glu Arg Gly Lys Ser Ser Gly Arg Ser Asp Asp Asn 130 135 140 Arg Glu Ser Leu Glu Lys Arg Ile Gln Thr Tyr Leu Gln Ser Thr Lys 145 150 155 160 Pro Ile Ile Asp Leu Tyr Glu Glu Met Gly Lys Val Lys Lys Ile Asp 165 170 175 Ala Ser Lys Ser Val Asp Glu Val Phe Asp Glu Val Val Gln Ile Phe 180 185 190 Asp Lys Glu Gly 195 <210> 74 <211> 630 <212> PRT <213> Homo sapiens <400> 74 Met Ala Leu Pro Thr Ala Arg Pro Leu Leu Gly Ser Cys Gly Thr Pro 1 5 10 15 Ala Leu Gly Ser Leu Leu Phe Leu Leu Phe Ser Leu Gly Trp Val Gln 20 25 30 Pro Ser Arg Thr Leu Ala Gly Glu Thr Gly Gln Glu Ala Ala Pro Leu 35 40 45 Asp Gly Val Leu Ala Asn Pro Pro Asn Ile Ser Ser Leu Ser Pro Arg 50 55 60 Gln Leu Leu Gly Phe Pro Cys Ala Glu Val Ser Gly Leu Ser Thr Glu 65 70 75 80 Arg Val Arg Glu Leu Ala Val Ala Leu Ala Gln Lys Asn Val Lys Leu 85 90 95 Ser Thr Glu Gln Leu Arg Cys Leu Ala His Arg Leu Ser Glu Pro Pro 100 105 110 Glu Asp Leu Asp Ala Leu Pro Leu Asp Leu Leu Leu Phe Leu Asn Pro 115 120 125 Asp Ala Phe Ser Gly Pro Gln Ala Cys Thr Arg Phe Phe Ser Arg Ile 130 135 140 Thr Lys Ala Asn Val Asp Leu Leu Pro Arg Gly Ala Pro Glu Arg Gln 145 150 155 160 Arg Leu Leu Pro Ala Ala Leu Ala Cys Trp Gly Val Arg Gly Ser Leu 165 170 175 Leu Ser Glu Ala Asp Val Arg Ala Leu Gly Gly Leu Ala Cys Asp Leu 180 185 190 Pro Gly Arg Phe Val Ala Glu Ser Ala Glu Val Leu Leu Pro Arg Leu 195 200 205 Val Ser Cys Pro Gly Pro Leu Asp Gln Asp Gln Gln Glu Ala Ala Arg 210 215 220 Ala Ala Leu Gln Gly Gly Gly Pro Pro Tyr Gly Pro Pro Ser Thr Trp 225 230 235 240 Ser Val Ser Thr Met Asp Ala Leu Arg Gly Leu Leu Pro Val Leu Gly 245 250 255 Gln Pro Ile Ile Arg Ser Ile Pro Gln Gly Ile Val Ala Ala Trp Arg 260 265 270 Gln Arg Ser Ser Arg Asp Pro Ser Trp Arg Gln Pro Glu Arg Thr Ile 275 280 285 Leu Arg Pro Arg Phe Arg Arg Glu Val Glu Lys Thr Ala Cys Pro Ser 290 295 300 Gly Lys Lys Ala Arg Glu Ile Asp Glu Ser Leu Ile Phe Tyr Lys Lys 305 310 315 320 Trp Glu Leu Glu Ala Cys Val Asp Ala Ala Leu Leu Ala Thr Gln Met 325 330 335 Asp Arg Val Asn Ala Ile Pro Phe Thr Tyr Glu Gln Leu Asp Val Leu 340 345 350 Lys His Lys Leu Asp Glu Leu Tyr Pro Gln Gly Tyr Pro Glu Ser Val 355 360 365 Ile Gln His Leu Gly Tyr Leu Phe Leu Lys Met Ser Pro Glu Asp Ile 370 375 380 Arg Lys Trp Asn Val Thr Ser Leu Glu Thr Leu Lys Ala Leu Leu Glu 385 390 395 400 Val Asn Lys Gly His Glu Met Ser Pro Gln Ala Pro Arg Arg Pro Leu 405 410 415 Pro Gln Val Ala Thr Leu Ile Asp Arg Phe Val Lys Gly Arg Gly Gln 420 425 430 Leu Asp Lys Asp Thr Leu Asp Thr Leu Thr Ala Phe Tyr Pro Gly Tyr 435 440 445 Leu Cys Ser Leu Ser Pro Glu Glu Leu Ser Ser Val Pro Pro Ser Ser 450 455 460 Ile Trp Ala Val Arg Pro Gln Asp Leu Asp Thr Cys Asp Pro Arg Gln 465 470 475 480 Leu Asp Val Leu Tyr Pro Lys Ala Arg Leu Ala Phe Gln Asn Met Asn 485 490 495 Gly Ser Glu Tyr Phe Val Lys Ile Gln Ser Phe Leu Gly Gly Ala Pro 500 505 510 Thr Glu Asp Leu Lys Ala Leu Ser Gln Gln Asn Val Ser Met Asp Leu 515 520 525 Ala Thr Phe Met Lys Leu Arg Thr Asp Ala Val Leu Pro Leu Thr Val 530 535 540 Ala Glu Val Gln Lys Leu Leu Gly Pro His Val Glu Gly Leu Lys Ala 545 550 555 560 Glu Glu Arg His Arg Pro Val Arg Asp Trp Ile Leu Arg Gln Arg Gln 565 570 575 Asp Asp Leu Asp Thr Leu Gly Leu Gly Leu Gln Gly Gly Ile Pro Asn 580 585 590 Gly Tyr Leu Val Leu Asp Leu Ser Met Gln Glu Ala Leu Ser Gly Thr 595 600 605 Pro Cys Leu Leu Gly Pro Gly Pro Val Leu Thr Val Leu Ala Leu Leu 610 615 620 Leu Ala Ser Thr Leu Ala 625 630 <210> 75 <211> 576 <212> PRT <213> Homo sapiens <400> 75 Met Ala Gln Gly Val Leu Trp Ile Leu Leu Gly Leu Leu Leu Trp Ser 1 5 10 15 Asp Pro Gly Thr Ala Ser Leu Pro Leu Leu Met Asp Ser Val Ile Gln 20 25 30 Ala Leu Ala Glu Leu Glu Gln Lys Val Pro Ala Ala Lys Thr Arg His 35 40 45 Thr Ala Ser Ala Trp Leu Met Ser Ala Pro Asn Ser Gly Pro His Asn 50 55 60 Arg Leu Tyr His Phe Leu Leu Gly Ala Trp Ser Leu Asn Ala Thr Glu 65 70 75 80 Leu Asp Pro Cys Pro Leu Ser Pro Glu Leu Leu Gly Leu Thr Lys Glu 85 90 95 Val Ala Arg His Asp Val Arg Glu Gly Lys Glu Tyr Gly Val Val Leu 100 105 110 Ala Pro Asp Gly Ser Thr Val Ala Val Glu Pro Leu Leu Ala Gly Leu 115 120 125 Glu Ala Gly Leu Gln Gly Arg Arg Val Ile Asn Leu Pro Leu Asp Ser 130 135 140 Met Ala Ala Pro Trp Glu Thr Gly Asp Thr Phe Pro Asp Val Val Ala 145 150 155 160 Ile Ala Pro Asp Val Arg Ala Thr Ser Ser Pro Gly Leu Arg Asp Gly 165 170 175 Ser Pro Asp Val Thr Thr Ala Asp Ile Gly Ala Asn Thr Pro Asp Ala 180 185 190 Thr Lys Gly Cys Pro Asp Val Gln Ala Ser Leu Pro Asp Ala Lys Ala 195 200 205 Lys Ser Pro Pro Thr Met Val Asp Ser Leu Leu Ala Val Thr Leu Ala 210 215 220 Gly Asn Leu Gly Leu Thr Phe Leu Arg Gly Ser Gln Thr Gln Ser His 225 230 235 240 Pro Asp Leu Gly Thr Glu Gly Cys Trp Asp Gln Leu Ser Ala Pro Arg 245 250 255 Thr Phe Thr Leu Leu Asp Pro Lys Ala Ser Leu Leu Thr Met Ala Phe 260 265 270 Leu Asn Gly Ala Leu Asp Gly Val Ile Leu Gly Asp Tyr Leu Ser Arg 275 280 285 Thr Pro Glu Pro Arg Pro Ser Leu Ser His Leu Leu Ser Gln Tyr Tyr 290 295 300 Gly Ala Gly Val Ala Arg Asp Pro Gly Phe Arg Ser Asn Phe Arg Arg 305 310 315 320 Gln Asn Gly Ala Ala Leu Thr Ser Ala Ser Ile Leu Ala Gln Gln Val 325 330 335 Trp Gly Thr Leu Val Leu Leu Gln Arg Leu Glu Pro Val His Leu Gln 340 345 350 Leu Gln Cys Met Ser Gln Glu Gln Leu Ala Gln Val Ala Ala Asn Ala 355 360 365 Thr Lys Glu Phe Thr Glu Ala Phe Leu Gly Cys Pro Ala Ile His Pro 370 375 380 Arg Cys Arg Trp Gly Ala Ala Pro Tyr Arg Gly Arg Pro Lys Leu Leu 385 390 395 400 Gln Leu Pro Leu Gly Phe Leu Tyr Val His His Thr Tyr Val Pro Ala 405 410 415 Pro Pro Cys Thr Asp Phe Thr Arg Cys Ala Ala Asn Met Arg Ser Met 420 425 430 Gln Arg Tyr His Gln Asp Thr Gln Gly Trp Gly Asp Ile Gly Tyr Ser 435 440 445 Phe Val Val Gly Ser Asp Gly Tyr Val Tyr Glu Gly Arg Gly Trp His 450 455 460 Trp Val Gly Ala His Thr Leu Gly His Asn Ser Arg Gly Phe Gly Val 465 470 475 480 Ala Ile Val Gly Asn Tyr Thr Ala Ala Leu Pro Thr Glu Ala Ala Leu 485 490 495 Arg Thr Val Arg Asp Thr Leu Pro Ser Cys Ala Val Arg Ala Gly Leu 500 505 510 Leu Arg Pro Asp Tyr Ala Leu Leu Gly His Arg Gln Leu Val Arg Thr 515 520 525 Asp Cys Pro Gly Asp Ala Leu Phe Asp Leu Leu Arg Thr Trp Pro His 530 535 540 Phe Thr Ala Thr Val Lys Pro Arg Pro Ala Arg Ser Val Ser Lys Arg 545 550 555 560 Ser Arg Arg Glu Pro Pro Pro Arg Thr Leu Pro Ala Thr Asp Leu Gln 565 570 575 <210> 76 <211> 538 <212> PRT <213> Homo sapiens <400> 76 Met Ala Ala Glu Gln Asp Pro Glu Ala Arg Ala Ala Ala Arg Pro Leu 1 5 10 15 Leu Thr Asp Leu Tyr Gln Ala Thr Met Ala Leu Gly Tyr Trp Arg Ala 20 25 30 Gly Arg Ala Arg Asp Ala Ala Glu Phe Glu Leu Phe Phe Arg Arg Cys 35 40 45 Pro Phe Gly Gly Ala Phe Ala Leu Ala Ala Gly Leu Arg Asp Cys Val 50 55 60 Arg Phe Leu Arg Ala Phe Arg Leu Arg Asp Ala Asp Val Gln Phe Leu 65 70 75 80 Ala Ser Val Leu Pro Pro Asp Thr Asp Pro Ala Phe Phe Glu His Leu 85 90 95 Arg Ala Leu Asp Cys Ser Glu Val Thr Val Arg Ala Leu Pro Glu Gly 100 105 110 Ser Leu Ala Phe Pro Gly Val Pro Leu Leu Gln Val Ser Gly Pro Leu 115 120 125 Leu Val Val Gln Leu Leu Glu Thr Pro Leu Leu Cys Leu Val Ser Tyr 130 135 140 Ala Ser Leu Val Ala Thr Asn Ala Ala Arg Leu Arg Leu Ile Ala Gly 145 150 155 160 Pro Glu Lys Arg Leu Leu Glu Met Gly Leu Arg Arg Ala Gln Gly Pro 165 170 175 Asp Gly Gly Leu Thr Ala Ser Thr Tyr Ser Tyr Leu Gly Gly Phe Asp 180 185 190 Ser Ser Ser Asn Val Leu Ala Gly Gln Leu Arg Gly Val Pro Val Ala 195 200 205 Gly Thr Leu Ala His Ser Phe Val Thr Ser Phe Ser Gly Ser Glu Val 210 215 220 Pro Pro Asp Pro Met Leu Ala Pro Ala Ala Gly Glu Gly Pro Gly Val 225 230 235 240 Asp Leu Ala Ala Lys Ala Gln Val Trp Leu Glu Gln Val Cys Ala His 245 250 255 Leu Gly Leu Gly Val Gln Glu Pro His Pro Gly Glu Arg Ala Ala Phe 260 265 270 Val Ala Tyr Ala Leu Ala Phe Pro Arg Ala Phe Gln Gly Leu Leu Asp 275 280 285 Thr Tyr Ser Val Trp Arg Ser Gly Leu Pro Asn Phe Leu Ala Val Ala 290 295 300 Leu Ala Leu Gly Glu Leu Gly Tyr Arg Ala Val Gly Val Arg Leu Asp 305 310 315 320 Ser Gly Asp Leu Leu Gln Gln Ala Gln Glu Ile Arg Lys Val Phe Arg 325 330 335 Ala Ala Ala Ala Gln Phe Gln Val Pro Trp Leu Glu Ser Val Leu Ile 340 345 350 Val Val Ser Asn Asn Ile Asp Glu Glu Ala Leu Ala Arg Leu Ala Gln 355 360 365 Glu Gly Ser Glu Val Asn Val Ile Gly Ile Gly Thr Ser Val Val Thr 370 375 380 Cys Pro Gln Gln Pro Ser Leu Gly Gly Val Tyr Lys Leu Val Ala Val 385 390 395 400 Gly Gly Gln Pro Arg Met Lys Leu Thr Glu Asp Pro Glu Lys Gln Thr 405 410 415 Leu Pro Gly Ser Lys Ala Ala Phe Arg Leu Leu Gly Ser Asp Gly Ser 420 425 430 Pro Leu Met Asp Met Leu Gln Leu Ala Glu Glu Pro Val Pro Gln Ala 435 440 445 Gly Gln Glu Leu Arg Val Trp Pro Pro Gly Ala Gln Glu Pro Cys Thr 450 455 460 Val Arg Pro Ala Gln Val Glu Pro Leu Leu Arg Leu Cys Leu Gln Gln 465 470 475 480 Gly Gln Leu Cys Glu Pro Leu Pro Ser Leu Ala Glu Ser Arg Ala Leu 485 490 495 Ala Gln Leu Ser Leu Ser Arg Leu Ser Pro Glu His Arg Arg Leu Arg 500 505 510 Ser Pro Ala Gln Tyr Gln Val Val Leu Ser Glu Arg Leu Gln Ala Leu 515 520 525 Val Asn Ser Leu Cys Ala Gly Gln Ser Pro 530 535 <210> 77 <211> 911 <212> PRT <213> Homo sapiens <400> 77 Met Asp Gly Ala Met Gly Pro Arg Gly Leu Leu Leu Cys Met Tyr Leu 1 5 10 15 Val Ser Leu Leu Ile Leu Gln Ala Met Pro Ala Leu Gly Ser Ala Thr 20 25 30 Gly Arg Ser Lys Ser Ser Glu Lys Arg Gln Ala Val Asp Thr Ala Val 35 40 45 Asp Gly Val Phe Ile Arg Ser Leu Lys Val Asn Cys Lys Val Thr Ser 50 55 60 Arg Phe Ala His Tyr Val Val Thr Ser Gln Val Val Asn Thr Ala Asn 65 70 75 80 Glu Ala Arg Glu Val Ala Phe Asp Leu Glu Ile Pro Lys Thr Ala Phe 85 90 95 Ile Ser Asp Phe Ala Val Thr Ala Asp Gly Asn Ala Phe Ile Gly Asp 100 105 110 Ile Lys Asp Lys Val Thr Ala Trp Lys Gln Tyr Arg Lys Ala Ala Ile 115 120 125 Ser Gly Glu Asn Ala Gly Leu Val Arg Ala Ser Gly Arg Thr Met Glu 130 135 140 Gln Phe Thr Ile His Leu Thr Val Asn Pro Gln Ser Lys Val Thr Phe 145 150 155 160 Gln Leu Thr Tyr Glu Glu Val Leu Lys Arg Asn His Met Gln Tyr Glu 165 170 175 Ile Val Ile Lys Val Lys Pro Lys Gln Leu Val His His Phe Glu Ile 180 185 190 Asp Val Asp Ile Phe Glu Pro Gln Gly Ile Ser Lys Leu Asp Ala Gln 195 200 205 Ala Ser Phe Leu Pro Lys Glu Leu Ala Ala Gln Thr Ile Lys Lys Ser 210 215 220 Phe Ser Gly Lys Lys Gly His Val Leu Phe Arg Pro Thr Val Ser Gln 225 230 235 240 Gln Gln Ser Cys Pro Thr Cys Ser Thr Ser Leu Leu Asn Gly His Phe 245 250 255 Lys Val Thr Tyr Asp Val Ser Arg Asp Lys Ile Cys Asp Leu Leu Val 260 265 270 Ala Asn Asn His Phe Ala His Phe Phe Ala Pro Gln Asn Leu Thr Asn 275 280 285 Met Asn Lys Asn Val Val Phe Val Ile Asp Ile Ser Gly Ser Met Arg 290 295 300 Gly Gln Lys Val Lys Gln Thr Lys Glu Ala Leu Leu Lys Ile Leu Gly 305 310 315 320 Asp Met Gln Pro Gly Asp Tyr Phe Asp Leu Val Leu Phe Gly Thr Arg 325 330 335 Val Gln Ser Trp Lys Gly Ser Leu Val Gln Ala Ser Glu Ala Asn Leu 340 345 350 Gln Ala Ala Gln Asp Phe Val Arg Gly Phe Ser Leu Asp Glu Ala Thr 355 360 365 Asn Leu Asn Gly Gly Leu Leu Arg Gly Ile Glu Ile Leu Asn Gln Val 370 375 380 Gln Glu Ser Leu Pro Glu Leu Ser Asn His Ala Ser Ile Leu Ile Met 385 390 395 400 Leu Thr Asp Gly Asp Pro Thr Glu Gly Val Thr Asp Arg Ser Gln Ile 405 410 415 Leu Lys Asn Val Arg Asn Ala Ile Arg Gly Arg Phe Pro Leu Tyr Asn 420 425 430 Leu Gly Phe Gly His Asn Val Asp Phe Asn Phe Leu Glu Val Met Ser 435 440 445 Met Glu Asn Asn Gly Arg Ala Gln Arg Ile Tyr Glu Asp His Asp Ala 450 455 460 Thr Gln Gln Leu Gln Gly Phe Tyr Ser Gln Val Ala Lys Pro Leu Leu 465 470 475 480 Val Asp Val Asp Leu Gln Tyr Pro Gln Asp Ala Val Leu Ala Leu Thr 485 490 495 Gln Asn His His Lys Gln Tyr Tyr Glu Gly Ser Glu Ile Val Val Ala 500 505 510 Gly Arg Ile Ala Asp Asn Lys Gln Ser Ser Phe Lys Ala Asp Val Gln 515 520 525 Ala His Gly Glu Gly Gln Glu Phe Ser Ile Thr Cys Leu Val Asp Glu 530 535 540 Glu Glu Met Lys Lys Leu Leu Arg Glu Arg Gly His Met Leu Glu Asn 545 550 555 560 His Val Glu Arg Leu Trp Ala Tyr Leu Thr Ile Gln Glu Leu Leu Ala 565 570 575 Lys Arg Met Lys Val Asp Arg Glu Glu Arg Ala Asn Leu Ser Ser Gln 580 585 590 Ala Leu Gln Met Ser Leu Asp Tyr Gly Phe Val Thr Pro Leu Thr Ser 595 600 605 Met Ser Ile Arg Gly Met Ala Asp Gln Asp Gly Leu Lys Pro Thr Ile 610 615 620 Asp Lys Pro Ser Glu Asp Ser Pro Pro Leu Glu Met Leu Gly Pro Arg 625 630 635 640 Arg Thr Phe Val Leu Ser Ala Leu Gln Pro Ser Pro Thr His Ser Ser 645 650 655 Ser Asn Thr Gln Arg Leu Pro Asp Arg Val Thr Gly Val Asp Thr Asp 660 665 670 Pro His Phe Ile Ile His Val Pro Gln Lys Glu Asp Thr Leu Cys Phe 675 680 685 Asn Ile Asn Glu Glu Pro Gly Val Ile Leu Ser Leu Val Gln Asp Pro 690 695 700 Asn Thr Gly Phe Ser Val Asn Gly Gln Leu Ile Gly Asn Lys Ala Arg 705 710 715 720 Ser Pro Gly Gln His Asp Gly Thr Tyr Phe Gly Arg Leu Gly Ile Ala 725 730 735 Asn Pro Ala Thr Asp Phe Gln Leu Glu Val Thr Pro Gln Asn Ile Thr 740 745 750 Leu Asn Pro Gly Phe Gly Gly Pro Val Phe Ser Trp Arg Asp Gln Ala 755 760 765 Val Leu Arg Gln Asp Gly Val Val Val Thr Ile Asn Lys Lys Arg Asn 770 775 780 Leu Val Val Ser Val Asp Asp Gly Gly Thr Phe Glu Val Val Leu His 785 790 795 800 Arg Val Trp Lys Gly Ser Ser Val His Gln Asp Phe Leu Gly Phe Tyr 805 810 815 Val Leu Asp Ser His Arg Met Ser Ala Arg Thr His Gly Leu Leu Gly 820 825 830 Gln Phe Phe His Pro Ile Gly Phe Glu Val Ser Asp Ile His Pro Gly 835 840 845 Ser Asp Pro Thr Lys Pro Asp Ala Thr Met Val Val Arg Asn Arg Arg 850 855 860 Leu Thr Val Thr Arg Gly Leu Gln Lys Asp Tyr Ser Lys Asp Pro Trp 865 870 875 880 His Gly Ala Glu Val Ser Cys Trp Phe Ile His Asn Asn Gly Ala Gly 885 890 895 Leu Ile Asp Gly Ala Tyr Thr Asp Tyr Ile Val Pro Asp Ile Phe 900 905 910 <210> 78 <211> 306 <212> PRT <213> Homo sapiens <400> 78 Met Arg Pro Ala Ala Leu Arg Gly Ala Leu Leu Gly Cys Leu Cys Leu 1 5 10 15 Ala Leu Leu Cys Leu Gly Gly Ala Asp Lys Arg Leu Arg Asp Asn His 20 25 30 Glu Trp Lys Lys Leu Ile Met Val Gln His Trp Pro Glu Thr Val Cys 35 40 45 Glu Lys Ile Gln Asn Asp Cys Arg Asp Pro Pro Asp Tyr Trp Thr Ile 50 55 60 His Gly Leu Trp Pro Asp Lys Ser Glu Gly Cys Asn Arg Ser Trp Pro 65 70 75 80 Phe Asn Leu Glu Glu Ile Lys Val Leu Thr Phe Asn Tyr Ile Ser Thr 85 90 95 Ala Glu Cys Ser Ser His Arg Leu Ser Ser Ser Pro Pro Gly Leu Thr 100 105 110 Ala Gly Asn Gly Phe Trp Gly Gly Ser Glu Glu Arg Cys Gly Arg Gly 115 120 125 Trp Pro Met Phe Leu Glu Gln Ile Lys Asp Leu Leu Pro Glu Met Arg 130 135 140 Ala Tyr Trp Pro Asp Val Ile His Ser Phe Pro Asn Arg Ser Arg Phe 145 150 155 160 Trp Lys His Glu Trp Glu Lys His Gly Thr Cys Ala Ala Gln Val Asp 165 170 175 Ala Leu Asn Ser Gln Lys Lys Tyr Phe Gly Arg Ser Leu Glu Leu Tyr 180 185 190 Arg Glu Leu Asp Leu Asn Ser Val Leu Leu Lys Leu Gly Ile Lys Pro 195 200 205 Ser Ile Asn Tyr Tyr Gln Val Ala Asp Phe Lys Asp Ala Leu Ala Arg 210 215 220 Val Tyr Gly Val Ile Pro Lys Ile Gln Cys Leu Pro Pro Ser Gln Asp 225 230 235 240 Glu Glu Val Gln Thr Ile Gly Gln Ile Glu Leu Cys Leu Thr Lys Gln 245 250 255 Asp Gln Gln Leu Gln Asn Cys Thr Glu Pro Gly Glu Gln Pro Ser Pro 260 265 270 Lys Gln Glu Val Trp Leu Ala Asn Gly Ala Ala Glu Ser Arg Gly Leu 275 280 285 Arg Val Cys Glu Asp Gly Pro Val Phe Tyr Pro Pro Pro Lys Lys Thr 290 295 300 Lys His 305 <210> 79 <211> 222 <212> PRT <213> Homo sapiens <400> 79 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> 80 <211> 169 <212> PRT <213> Homo sapiens <400> 80 Met Ser Ser Tyr Gln Gln Lys Gln Thr Phe Thr Pro Pro Pro Gln Leu 1 5 10 15 Gln Gln Gln Gln Val Lys Gln Pro Ser Gln Pro Pro Pro Gln Glu Ile 20 25 30 Phe Val Pro Thr Thr Lys Glu Pro Cys His Ser Lys Val Pro Gln Pro 35 40 45 Gly Asn Thr Lys Ile Pro Glu Pro Gly Cys Thr Lys Val Pro Glu Pro 50 55 60 Gly Cys Thr Lys Val Pro Glu Pro Gly Cys Thr Lys Val Pro Glu Pro 65 70 75 80 Gly Cys Thr Lys Val Pro Glu Pro Gly Cys Thr Lys Val Pro Glu Pro 85 90 95 Gly Cys Thr Lys Val Pro Glu Pro Gly Tyr Thr Lys Val Pro Glu Pro 100 105 110 Gly Ser Ile Lys Val Pro Asp Gln Gly Phe Ile Lys Phe Pro Glu Pro 115 120 125 Gly Ala Ile Lys Val Pro Glu Gln Gly Tyr Thr Lys Val Pro Val Pro 130 135 140 Gly Tyr Thr Lys Leu Pro Glu Pro Cys Pro Ser Thr Val Thr Pro Gly 145 150 155 160 Pro Ala Gln Gln Lys Thr Lys Gln Lys 165 <210> 81 <211> 550 <212> PRT <213> Homo sapiens <400> 81 Met Trp Lys Ala Ser Ala Gly His Ala Val Ser Ile Ala Gln Asp Asp 1 5 10 15 Ala Gly Ala Asp Asp Trp Glu Thr Asp Pro Asp Phe Val Asn Asp Val 20 25 30 Ser Glu Lys Glu Gln Arg Trp Gly Ala Lys Thr Val Gln Gly Ser Gly 35 40 45 His Gln Glu His Ile Asn Ile His Lys Leu Arg Glu Asn Val Phe Gln 50 55 60 Glu His Gln Thr Leu Lys Glu Lys Glu Leu Glu Thr Gly Pro Lys Ala 65 70 75 80 Ser His Gly Tyr Gly Gly Lys Phe Gly Val Glu Gln Asp Arg Met Asp 85 90 95 Lys Ser Ala Val Gly His Glu Tyr Gln Ser Lys Leu Ser Lys His Cys 100 105 110 Ser Gln Val Asp Ser Val Arg Gly Phe Gly Gly Lys Phe Gly Val Gln 115 120 125 Met Asp Arg Val Asp Gln Ser Ala Val Gly Phe Glu Tyr Gln Gly Lys 130 135 140 Thr Glu Lys His Ala Ser Gln Lys Asp Tyr Ser Ser Gly Phe Gly Gly 145 150 155 160 Lys Tyr Gly Val Gln Ala Asp Arg Val Asp Lys Ser Ala Val Gly Phe 165 170 175 Asp Tyr Gln Gly Lys Thr Glu Lys His Glu Ser Gln Arg Asp Tyr Ser 180 185 190 Lys Gly Phe Gly Gly Lys Tyr Gly Ile Asp Lys Asp Lys Val Asp Lys 195 200 205 Ser Ala Val Gly Phe Glu Tyr Gln Gly Lys Thr Glu Lys His Glu Ser 210 215 220 Gln Lys Asp Tyr Val Lys Gly Phe Gly Gly Lys Phe Gly Val Gln Thr 225 230 235 240 Asp Arg Gln Asp Lys Cys Ala Leu Gly Trp Asp His Gln Glu Lys Leu 245 250 255 Gln Leu His Glu Ser Gln Lys Asp Tyr Lys Thr Gly Phe Gly Gly Lys 260 265 270 Phe Gly Val Gln Ser Glu Arg Gln Asp Ser Ala Ala Val Gly Phe Asp 275 280 285 Tyr Lys Glu Lys Leu Ala Lys His Glu Ser Gln Gln Asp Tyr Ser Lys 290 295 300 Gly Phe Gly Gly Lys Tyr Gly Val Gln Lys Asp Arg Met Asp Lys Asn 305 310 315 320 Ala Ser Thr Phe Glu Asp Val Thr Gln Val Ser Ser Ala Tyr Gln Lys 325 330 335 Thr Val Pro Val Glu Ala Val Thr Ser Lys Thr Ser Asn Ile Arg Ala 340 345 350 Asn Phe Glu Asn Leu Ala Lys Glu Lys Glu Gln Glu Asp Arg Arg Lys 355 360 365 Ala Glu Ala Glu Arg Ala Gln Arg Met Ala Lys Glu Arg Gln Glu Gln 370 375 380 Glu Glu Ala Arg Arg Lys Leu Glu Glu Gln Ala Arg Ala Lys Thr Gln 385 390 395 400 Thr Pro Pro Val Ser Pro Ala Pro Gln Pro Thr Glu Glu Arg Leu Pro 405 410 415 Ser Ser Pro Val Tyr Glu Asp Ala Ala Ser Phe Lys Ala Glu Leu Ser 420 425 430 Tyr Arg Gly Pro Val Ser Gly Thr Glu Pro Glu Pro Val Tyr Ser Met 435 440 445 Glu Ala Ala Asp Tyr Arg Glu Ala Ser Ser Gln Gln Gly Leu Ala Tyr 450 455 460 Ala Thr Glu Ala Val Tyr Glu Ser Ala Glu Ala Pro Gly His Tyr Pro 465 470 475 480 Ala Glu Asp Ser Thr Tyr Asp Glu Tyr Glu Asn Asp Leu Gly Ile Thr 485 490 495 Ala Val Ala Leu Tyr Asp Tyr Gln Ala Ala Gly Asp Asp Glu Ile Ser 500 505 510 Phe Asp Pro Asp Asp Ile Ile Thr Asn Ile Glu Met Ile Asp Asp Gly 515 520 525 Trp Trp Arg Gly Val Cys Lys Gly Arg Tyr Gly Leu Phe Pro Ala Asn 530 535 540 Tyr Val Glu Leu Arg Gln 545 550 <210> 82 <211> 445 <212> PRT <213> Homo sapiens <400> 82 Met Arg Glu Ile Val His Leu Gln Ala Gly Gln Cys Gly Asn Gln Ile 1 5 10 15 Gly Ala Lys Phe Trp Glu Val Ile Ser Asp Glu His Gly Ile Asp Pro 20 25 30 Thr Gly Thr Tyr His Gly Asp Ser Asp Leu Gln Leu Glu Arg Ile Asn 35 40 45 Val Tyr Tyr Asn Glu Ala Thr Gly Gly Lys Tyr Val Pro Arg Ala Val 50 55 60 Leu Val Asp Leu Glu Pro Gly Thr Met Asp Ser Val Arg Ser Gly Pro 65 70 75 80 Phe Gly Gln Ile Phe Arg Pro Asp Asn Phe Val Phe Gly Gln Ser Gly 85 90 95 Ala Gly Asn Asn Trp Ala Lys Gly His Tyr Thr Glu Gly Ala Glu Leu 100 105 110 Val Asp Ser Val Leu Asp Val Val Arg Lys Glu Ala Glu Ser Cys Asp 115 120 125 Cys Leu Gln Gly Phe Gln Leu Thr His Ser Leu Gly Gly Gly Thr Gly 130 135 140 Ser Gly Met Gly Thr Leu Leu Ile Ser Lys Ile Arg Glu Glu Tyr Pro 145 150 155 160 Asp Arg Ile Met Asn Thr Phe Ser Val Val Pro Ser Pro Lys Val Ser 165 170 175 Asp Thr Val Val Glu Pro Tyr Asn Ala Thr Leu Ser Val His Gln Leu 180 185 190 Val Glu Asn Thr Asp Glu Thr Tyr Cys Ile Asp Asn Glu Ala Leu Tyr 195 200 205 Asp Ile Cys Phe Arg Thr Leu Lys Leu Thr Thr Pro Thr Tyr Gly Asp 210 215 220 Leu Asn His Leu Val Ser Ala Thr Met Ser Gly Val Thr Thr Cys Leu 225 230 235 240 Arg Phe Pro Gly Gln Leu Asn Ala Asp Leu Arg Lys Leu Ala Val Asn 245 250 255 Met Val Pro Phe Pro Arg Leu His Phe Phe Met Pro Gly Phe Ala Pro 260 265 270 Leu Thr Ser Arg Gly Ser Gln Gln Tyr Arg Ala Leu Thr Val Pro Glu 275 280 285 Leu Thr Gln Gln Met Phe Asp Ala Lys Asn Met Met Ala Ala Cys Asp 290 295 300 Pro Arg His Gly Arg Tyr Leu Thr Val Ala Ala Val Phe Arg Gly Arg 305 310 315 320 Met Ser Met Lys Glu Val Asp Glu Gln Met Leu Asn Val Gln Asn Lys 325 330 335 Asn Ser Ser Tyr Phe Val Glu Trp Ile Pro Asn Asn Val Lys Thr Ala 340 345 350 Val Cys Asp Ile Pro Pro Arg Gly Leu Lys Met Ser Ala Thr Phe Ile 355 360 365 Gly Asn Ser Thr Ala Ile Gln Glu Leu Phe Lys Arg Ile Ser Glu Gln 370 375 380 Phe Thr Ala Met Phe Arg Arg Lys Ala Phe Leu His Trp Tyr Thr Gly 385 390 395 400 Glu Gly Met Asp Glu Met Glu Phe Thr Glu Ala Glu Ser Asn Met Asn 405 410 415 Asp Leu Val Ser Glu Tyr Gln Gln Tyr Gln Asp Ala Thr Ala Glu Glu 420 425 430 Glu Gly Glu Phe Glu Glu Glu Ala Glu Glu Glu Val Ala 435 440 445 <210> 83 <211> 227 <212> PRT <213> Homo sapiens <400> 83 Met Ala Gly Ile Thr Thr Ile Glu Ala Val Lys Arg Lys Ile Gln Val 1 5 10 15 Leu Gln Gln Gln Ala Asp Asp Ala Glu Glu Arg Ala Glu Arg Leu Gln 20 25 30 Arg Glu Val Glu Gly Glu Arg Arg Ala Arg Glu Gln Ala Glu Ala Glu 35 40 45 Val Ala Ser Leu Asn Arg Arg Ile Gln Leu Val Glu Glu Glu Leu Asp 50 55 60 Arg Ala Gln Glu Arg Leu Ala Thr Ala Leu Gln Lys Leu Glu Glu Ala 65 70 75 80 Glu Lys Ala Ala Asp Glu Ser Glu Arg Gly Met Lys Val Ile Glu Asn 85 90 95 Arg Ala Leu Lys Asp Glu Glu Lys Met Glu Leu Gln Glu Ile Gln Leu 100 105 110 Lys Glu Ala Lys His Ile Ala Glu Glu Ala Asp Arg Lys Tyr Glu Glu 115 120 125 Val Ala Arg Lys Leu Val Ile Ile Glu Gly Asp Leu Glu Arg Thr Glu 130 135 140 Glu Arg Ala Glu Leu Ala Glu Ser Arg Cys Arg Glu Met Asp Glu Gln 145 150 155 160 Ile Arg Leu Met Asp Gln Asn Leu Lys Cys Leu Ser Ala Ala Glu Glu 165 170 175 Lys Ala Glu Thr Arg Ala Glu Phe Ala Glu Arg Ser Val Ala Lys Leu 180 185 190 Glu Lys Thr Ile Asp Asp Leu Glu Asp Lys Leu Lys Cys Thr Lys Glu 195 200 205 Glu His Leu Cys Thr Gln Arg Met Leu Asp Gln Thr Leu Leu Asp Leu 210 215 220 Asn Glu Met 225 <210> 84 <211> 698 <212> PRT <213> Homo sapiens <400> 84 Met Arg Leu Ala Val Gly Ala Leu Leu Val Cys Ala Val Leu Gly Leu 1 5 10 15 Cys Leu Ala Val Pro Asp Lys Thr Val Arg Trp Cys Ala Val Ser Glu 20 25 30 His Glu Ala Thr Lys Cys Gln Ser Phe Arg Asp His Met Lys Ser Val 35 40 45 Ile Pro Ser Asp Gly Pro Ser Val Ala Cys Val Lys Lys Ala Ser Tyr 50 55 60 Leu Asp Cys Ile Arg Ala Ile Ala Ala Asn Glu Ala Asp Ala Val Thr 65 70 75 80 Leu Asp Ala Gly Leu Val Tyr Asp Ala Tyr Leu Ala Pro Asn Asn Leu 85 90 95 Lys Pro Val Val Ala Glu Phe Tyr Gly Ser Lys Glu Asp Pro Gln Thr 100 105 110 Phe Tyr Tyr Ala Val Ala Val Val Lys Lys Asp Ser Gly Phe Gln Met 115 120 125 Asn Gln Leu Arg Gly Lys Lys Ser Cys His Thr Gly Leu Gly Arg Ser 130 135 140 Ala Gly Trp Asn Ile Pro Ile Gly Leu Leu Tyr Cys Asp Leu Pro Glu 145 150 155 160 Pro Arg Lys Pro Leu Glu Lys Ala Val Ala Asn Phe Phe Ser Gly Ser 165 170 175 Cys Ala Pro Cys Ala Asp Gly Thr Asp Phe Pro Gln Leu Cys Gln Leu 180 185 190 Cys Pro Gly Cys Gly Cys Ser Thr Leu Asn Gln Tyr Phe Gly Tyr Ser 195 200 205 Gly Ala Phe Lys Cys Leu Lys Asp Gly Ala Gly Asp Val Ala Phe Val 210 215 220 Lys His Ser Thr Ile Phe Glu Asn Leu Ala Asn Lys Ala Asp Arg Asp 225 230 235 240 Gln Tyr Glu Leu Leu Cys Leu Asp Asn Thr Arg Lys Pro Val Asp Glu 245 250 255 Tyr Lys Asp Cys His Leu Ala Gln Val Pro Ser His Thr Val Val Ala 260 265 270 Arg Ser Met Gly Gly Lys Glu Asp Leu Ile Trp Glu Leu Leu Asn Gln 275 280 285 Ala Gln Glu His Phe Gly Lys Asp Lys Ser Lys Glu Phe Gln Leu Phe 290 295 300 Ser Ser Pro His Gly Lys Asp Leu Leu Phe Lys Asp Ser Ala His Gly 305 310 315 320 Phe Leu Lys Val Pro Pro Arg Met Asp Ala Lys Met Tyr Leu Gly Tyr 325 330 335 Glu Tyr Val Thr Ala Ile Arg Asn Leu Arg Glu Gly Thr Cys Pro Glu 340 345 350 Ala Pro Thr Asp Glu Cys Lys Pro Val Lys Trp Cys Ala Leu Ser His 355 360 365 His Glu Arg Leu Lys Cys Asp Glu Trp Ser Val Asn Ser Val Gly Lys 370 375 380 Ile Glu Cys Val Ser Ala Glu Thr Thr Glu Asp Cys Ile Ala Lys Ile 385 390 395 400 Met Asn Gly Glu Ala Asp Ala Met Ser Leu Asp Gly Gly Phe Val Tyr 405 410 415 Ile Ala Gly Lys Cys Gly Leu Val Pro Val Leu Ala Glu Asn Tyr Asn 420 425 430 Lys Ser Asp Asn Cys Glu Asp Thr Pro Glu Ala Gly Tyr Phe Ala Ile 435 440 445 Ala Val Val Lys Lys Ser Ala Ser Asp Leu Thr Trp Asp Asn Leu Lys 450 455 460 Gly Lys Lys Ser Cys His Thr Ala Val Gly Arg Thr Ala Gly Trp Asn 465 470 475 480 Ile Pro Met Gly Leu Leu Tyr Asn Lys Ile Asn His Cys Arg Phe Asp 485 490 495 Glu Phe Phe Ser Glu Gly Cys Ala Pro Gly Ser Lys Lys Asp Ser Ser 500 505 510 Leu Cys Lys Leu Cys Met Gly Ser Gly Leu Asn Leu Cys Glu Pro Asn 515 520 525 Asn Lys Glu Gly Tyr Tyr Gly Tyr Thr Gly Ala Phe Arg Cys Leu Val 530 535 540 Glu Lys Gly Asp Val Ala Phe Val Lys His Gln Thr Val Pro Gln Asn 545 550 555 560 Thr Gly Gly Lys Asn Pro Asp Pro Trp Ala Lys Asn Leu Asn Glu Lys 565 570 575 Asp Tyr Glu Leu Leu Cys Leu Asp Gly Thr Arg Lys Pro Val Glu Glu 580 585 590 Tyr Ala Asn Cys His Leu Ala Arg Ala Pro Asn His Ala Val Val Thr 595 600 605 Arg Lys Asp Lys Glu Ala Cys Val His Lys Ile Leu Arg Gln Gln Gln 610 615 620 His Leu Phe Gly Ser Asn Val Thr Asp Cys Ser Gly Asn Phe Cys Leu 625 630 635 640 Phe Arg Ser Glu Thr Lys Asp Leu Leu Phe Arg Asp Asp Thr Val Cys 645 650 655 Leu Ala Lys Leu His Asp Arg Asn Thr Tyr Glu Lys Tyr Leu Gly Glu 660 665 670 Glu Tyr Val Lys Ala Val Gly Asn Leu Arg Lys Cys Ser Thr Ser Ser 675 680 685 Leu Leu Glu Ala Cys Thr Phe Arg Arg Pro 690 695 <210> 85 <211> 210 <212> PRT <213> Homo sapiens <400> 85 Met Pro Pro Tyr Thr Val Val Tyr Phe Pro Val Arg Gly Arg Cys Ala 1 5 10 15 Ala Leu Arg Met Leu Leu Ala Asp Gln Gly Gln Ser Trp Lys Glu Glu 20 25 30 Val Val Thr Val Glu Thr Trp Gln Glu Gly Ser Leu Lys Ala Ser Cys 35 40 45 Leu Tyr Gly Gln Leu Pro Lys Phe Gln Asp Gly Asp Leu Thr Leu Tyr 50 55 60 Gln Ser Asn Thr Ile Leu Arg His Leu Gly Arg Thr Leu Gly Leu Tyr 65 70 75 80 Gly Lys Asp Gln Gln Glu Ala Ala Leu Val Asp Met Val Asn Asp Gly 85 90 95 Val Glu Asp Leu Arg Cys Lys Tyr Ile Ser Leu Ile Tyr Thr Asn Tyr 100 105 110 Glu Ala Gly Lys Asp Asp Tyr Val Lys Ala Leu Pro Gly Gln Leu Lys 115 120 125 Pro Phe Glu Thr Leu Leu Ser Gln Asn Gln Gly Gly Lys Thr Phe Ile 130 135 140 Val Gly Asp Gln Ile Ser Phe Ala Asp Tyr Asn Leu Leu Asp Leu Leu 145 150 155 160 Leu Ile His Glu Val Leu Ala Pro Gly Cys Leu Asp Ala Phe Pro Leu 165 170 175 Leu Ser Ala Tyr Val Gly Arg Leu Ser Ala Arg Pro Lys Leu Lys Ala 180 185 190 Phe Leu Ala Ser Pro Glu Tyr Val Asn Leu Pro Ile Asn Gly Asn Gly 195 200 205 Lys Gln 210 <210> 86 <211> 478 <212> PRT <213> Homo sapiens <400> 86 Met Ala Pro Leu Arg Pro Leu Leu Ile Leu Ala Leu Leu Ala Trp Val 1 5 10 15 Ala Leu Ala Asp Gln Glu Ser Cys Lys Gly Arg Cys Thr Glu Gly Phe 20 25 30 Asn Val Asp Lys Lys Cys Gln Cys Asp Glu Leu Cys Ser Tyr Tyr Gln 35 40 45 Ser Cys Cys Thr Asp Tyr Thr Ala Glu Cys Lys Pro Gln Val Thr Arg 50 55 60 Gly Asp Val Phe Thr Met Pro Glu Asp Glu Tyr Thr Val Tyr Asp Asp 65 70 75 80 Gly Glu Glu Lys Asn Asn Ala Thr Val His Glu Gln Val Gly Gly Pro 85 90 95 Ser Leu Thr Ser Asp Leu Gln Ala Gln Ser Lys Gly Asn Pro Glu Gln 100 105 110 Thr Pro Val Leu Lys Pro Glu Glu Glu Ala Pro Ala Pro Glu Val Gly 115 120 125 Ala Ser Lys Pro Glu Gly Ile Asp Ser Arg Pro Glu Thr Leu His Pro 130 135 140 Gly Arg Pro Gln Pro Pro Ala Glu Glu Glu Leu Cys Ser Gly Lys Pro 145 150 155 160 Phe Asp Ala Phe Thr Asp Leu Lys Asn Gly Ser Leu Phe Ala Phe Arg 165 170 175 Gly Gln Tyr Cys Tyr Glu Leu Asp Glu Lys Ala Val Arg Pro Gly Tyr 180 185 190 Pro Lys Leu Ile Arg Asp Val Trp Gly Ile Glu Gly Pro Ile Asp Ala 195 200 205 Ala Phe Thr Arg Ile Asn Cys Gln Gly Lys Thr Tyr Leu Phe Lys Gly 210 215 220 Ser Gln Tyr Trp Arg Phe Glu Asp Gly Val Leu Asp Pro Asp Tyr Pro 225 230 235 240 Arg Asn Ile Ser Asp Gly Phe Asp Gly Ile Pro Asp Asn Val Asp Ala 245 250 255 Ala Leu Ala Leu Pro Ala His Ser Tyr Ser Gly Arg Glu Arg Val Tyr 260 265 270 Phe Phe Lys Gly Lys Gln Tyr Trp Glu Tyr Gln Phe Gln His Gln Pro 275 280 285 Ser Gln Glu Glu Cys Glu Gly Ser Ser Leu Ser Ala Val Phe Glu His 290 295 300 Phe Ala Met Met Gln Arg Asp Ser Trp Glu Asp Ile Phe Glu Leu Leu 305 310 315 320 Phe Trp Gly Arg Thr Ser Ala Gly Thr Arg Gln Pro Gln Phe Ile Ser 325 330 335 Arg Asp Trp His Gly Val Pro Gly Gln Val Asp Ala Ala Met Ala Gly 340 345 350 Arg Ile Tyr Ile Ser Gly Met Ala Pro Arg Pro Ser Leu Ala Lys Lys 355 360 365 Gln Arg Phe Arg His Arg Asn Arg Lys Gly Tyr Arg Ser Gln Arg Gly 370 375 380 His Ser Arg Gly Arg Asn Gln Asn Ser Arg Arg Pro Ser Arg Ala Thr 385 390 395 400 Trp Leu Ser Leu Phe Ser Ser Glu Glu Ser Asn Leu Gly Ala Asn Asn 405 410 415 Tyr Asp Asp Tyr Arg Met Asp Trp Leu Val Pro Ala Thr Cys Glu Pro 420 425 430 Ile Gln Ser Val Phe Phe Phe Ser Gly Asp Lys Tyr Tyr Arg Val Asn 435 440 445 Leu Arg Thr Arg Arg Val Asp Thr Val Asp Pro Pro Tyr Pro Arg Ser 450 455 460 Ile Ala Gln Tyr Trp Leu Gly Cys Pro Ala Pro Gly His Leu 465 470 475 <210> 87 <211> 114 <212> PRT <213> Homo sapiens <400> 87 Met Thr Cys Lys Met Ser Gln Leu Glu Arg Asn Ile Glu Thr Ile Ile 1 5 10 15 Asn Thr Phe His Gln Tyr Ser Val Lys Leu Gly His Pro Asp Thr Leu 20 25 30 Asn Gln Gly Glu Phe Lys Glu Leu Val Arg Lys Asp Leu Gln Asn Phe 35 40 45 Leu Lys Lys Glu Asn Lys Asn Glu Lys Val Ile Glu His Ile Met Glu 50 55 60 Asp Leu Asp Thr Asn Ala Asp Lys Gln Leu Ser Phe Glu Glu Phe Ile 65 70 75 80 Met Leu Met Ala Arg Leu Thr Trp Ala Ser His Glu Lys Met His Glu 85 90 95 Gly Asp Glu Gly Pro Gly His His His Lys Pro Gly Leu Gly Glu Gly 100 105 110 Thr Pro <210> 88 <211> 15 <212> PRT <213> Homo sapiens <400> 88 Ser Cys Cys Glu Glu Gln Asn Lys Val Asn Cys Leu Gln Thr Arg 1 5 10 15 <210> 89 <211> 14 <212> PRT <213> Homo sapiens <400> 89 Ala Glu Ser Pro Glu Val Cys Phe Asn Glu Glu Ser Pro Lys 1 5 10 <210> 90 <211> 14 <212> PRT <213> Homo sapiens <400> 90 Glu Gly Lys Phe Thr Asp Ser Glu Asn Val Cys Gln Glu Arg 1 5 10 <210> 91 <211> 13 <212> PRT <213> Homo sapiens <400> 91 Glu Ser Leu Leu Asn His Phe Leu Tyr Glu Val Ala Arg 1 5 10 <210> 92 <211> 11 <212> PRT <213> Homo sapiens <400> 92 Phe Thr Asp Ser Glu Asn Val Cys Gln Glu Arg 1 5 10 <210> 93 <211> 12 <212> PRT <213> Homo sapiens <400> 93 Arg His Pro Asp Leu Ser Ile Pro Glu Leu Leu Arg 1 5 10 <210> 94 <211> 17 <212> PRT <213> Homo sapiens <400> 94 Ser Asp Val Gly Phe Leu Pro Pro Phe Pro Thr Leu Asp Pro Glu Glu 1 5 10 15 Lys <210> 95 <211> 28 <212> PRT <213> Homo sapiens <400> 95 Cys Ser Pro His Leu Val Leu Ser Ala Leu Thr Ser Asp Asn His Gly 1 5 10 15 Ala Thr Tyr Ala Phe Ser Gly Thr His Tyr Trp Arg 20 25 <210> 96 <211> 9 <212> PRT <213> Homo sapiens <400> 96 Asp Tyr Phe Met Pro Cys Pro Gly Arg 1 5 <210> 97 <211> 24 <212> PRT <213> Homo sapiens <400> 97 Glu Val Gly Thr Pro His Gly Ile Ile Leu Asp Ser Val Asp Ala Ala 1 5 10 15 Phe Ile Cys Pro Gly Ser Ser Arg 20 <210> 98 <211> 14 <212> PRT <213> Homo sapiens <400> 98 Glu Trp Phe Trp Asp Leu Ala Thr Gly Thr Met Lys Glu Arg 1 5 10 <210> 99 <211> 12 <212> PRT <213> Homo sapiens <400> 99 Gly Asp Lys Val Trp Val Tyr Pro Pro Glu Lys Lys 1 5 10 <210> 100 <211> 15 <212> PRT <213> Homo sapiens <400> 100 Gly Glu Cys Gln Ala Glu Gly Val Leu Phe Phe Gln Gly Asp Arg 1 5 10 15 <210> 101 <211> 11 <212> PRT <213> Homo sapiens <400> 101 Gly Gly Tyr Thr Leu Val Ser Gly Tyr Pro Lys 1 5 10 <210> 102 <211> 21 <212> PRT <213> Homo sapiens <400> 102 Leu Leu Gln Asp Glu Phe Pro Gly Ile Pro Ser Pro Leu Asp Ala Ala 1 5 10 15 Val Glu Cys His Arg 20 <210> 103 <211> 11 <212> PRT <213> Homo sapiens <400> 103 Asn Phe Pro Ser Pro Val Asp Ala Ala Phe Arg 1 5 10 <210> 104 <211> 10 <212> PRT <213> Homo sapiens <400> 104 Gln Gly His Asn Ser Val Phe Leu Ile Lys 1 5 10 <210> 105 <211> 8 <212> PRT <213> Homo sapiens <400> 105 Arg Leu Trp Trp Leu Asp Leu Lys 1 5 <210> 106 <211> 16 <212> PRT <213> Homo sapiens <400> 106 Ser Gly Ala Gln Ala Thr Trp Thr Glu Leu Pro Trp Pro His Glu Lys 1 5 10 15 <210> 107 <211> 30 <212> PRT <213> Homo sapiens <400> 107 Ser Leu Gly Pro Asn Ser Cys Ser Ala Asn Gly Pro Gly Leu Tyr Leu 1 5 10 15 Ile His Gly Pro Asn Leu Tyr Cys Tyr Ser Asp Val Glu Lys 20 25 30 <210> 108 <211> 35 <212> PRT <213> Homo sapiens <400> 108 Ser Leu Gly Pro Asn Ser Cys Ser Ala Asn Gly Pro Gly Leu Tyr Leu 1 5 10 15 Ile His Gly Pro Asn Leu Tyr Cys Tyr Ser Asp Val Glu Lys Leu Asn 20 25 30 Ala Ala Lys 35 <210> 109 <211> 9 <212> PRT <213> Homo sapiens <400> 109 Val Trp Val Tyr Pro Pro Glu Lys Lys 1 5 <210> 110 <211> 13 <212> PRT <213> Homo sapiens <400> 110 Trp Lys Asn Phe Pro Ser Pro Val Asp Ala Ala Phe Arg 1 5 10 <210> 111 <211> 15 <212> PRT <213> Homo sapiens <400> 111 Trp Leu Gly Arg Tyr Tyr Cys Phe Gln Gly Asn Gln Phe Leu Arg 1 5 10 15 <210> 112 <211> 11 <212> PRT <213> Homo sapiens <400> 112 Tyr Tyr Cys Phe Gln Gly Asn Gln Phe Leu Arg 1 5 10 <210> 113 <211> 20 <212> PRT <213> Homo sapiens <400> 113 Ala Asp Glu Ile Ala Lys Ala Gln Val Ala Arg Pro Gly Gly Asp Thr 1 5 10 15 Ile Phe Gly Lys 20 <210> 114 <211> 20 <212> PRT <213> Homo sapiens <400> 114 Cys Leu Ala Phe His Asp Ile Ser Pro Gln Ala Pro Thr His Phe Leu 1 5 10 15 Val Ile Pro Lys 20 <210> 115 <211> 26 <212> PRT <213> Homo sapiens <400> 115 Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro 1 5 10 15 Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 20 25 <210> 116 <211> 14 <212> PRT <213> Homo sapiens <400> 116 Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys 1 5 10 <210> 117 <211> 7 <212> PRT <213> Homo sapiens <400> 117 Asp Thr Leu Met Ile Ser Arg 1 5 <210> 118 <211> 12 <212> PRT <213> Homo sapiens <400> 118 Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg 1 5 10 <210> 119 <211> 27 <212> PRT <213> Homo sapiens <400> 119 Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly 1 5 10 15 Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 20 25 <210> 120 <211> 10 <212> PRT <213> Homo sapiens <400> 120 Asn Gln Val Ser Leu Thr Cys Leu Val Lys 1 5 10 <210> 121 <211> 14 <212> PRT <213> Homo sapiens <400> 121 Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys 1 5 10 <210> 122 <211> 17 <212> PRT <213> Homo sapiens <400> 122 Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser 1 5 10 15 Arg <210> 123 <211> 17 <212> PRT <213> Homo sapiens <400> 123 Thr Thr Pro Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 1 5 10 15 Lys <210> 124 <211> 12 <212> PRT <213> Homo sapiens <400> 124 Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys 1 5 10 <210> 125 <211> 16 <212> PRT <213> Homo sapiens <400> 125 Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys 1 5 10 15 <210> 126 <211> 19 <212> PRT <213> Homo sapiens <400> 126 Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys 1 5 10 15 Glu Tyr Lys <210> 127 <211> 11 <212> PRT <213> Homo sapiens <400> 127 Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Lys 1 5 10 <210> 128 <211> 19 <212> PRT <213> Homo sapiens <400> 128 Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg <210> 129 <211> 19 <212> PRT <213> Homo sapiens <400> 129 Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln 1 5 10 15 Ala Asn Lys <210> 130 <211> 17 <212> PRT <213> Homo sapiens <400> 130 Ala Asp Ser Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser 1 5 10 15 Lys <210> 131 <211> 22 <212> PRT <213> Homo sapiens <400> 131 Ala Asp Ser Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser 1 5 10 15 Lys Gln Ser Asn Asn Lys 20 <210> 132 <211> 10 <212> PRT <213> Homo sapiens <400> 132 Ala Gly Val Glu Thr Thr Thr Pro Ser Lys 1 5 10 <210> 133 <211> 30 <212> PRT <213> Homo sapiens <400> 133 Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr 1 5 10 15 Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys 20 25 30 <210> 134 <211> 20 <212> PRT <213> Homo sapiens <400> 134 Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro 1 5 10 15 Glu Gln Trp Lys 20 <210> 135 <211> 18 <212> PRT <213> Homo sapiens <400> 135 Ser His Lys Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val 1 5 10 15 Glu Lys <210> 136 <211> 15 <212> PRT <213> Homo sapiens <400> 136 Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys 1 5 10 15 <210> 137 <211> 23 <212> PRT <213> Homo sapiens <400> 137 Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr 1 5 10 15 Val Ala Pro Thr Glu Cys Ser 20 <210> 138 <211> 8 <212> PRT <213> Homo sapiens <400> 138 Thr Val Ala Pro Thr Glu Cys Ser 1 5 <210> 139 <211> 15 <212> PRT <213> Homo sapiens <400> 139 Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys 1 5 10 15 <210> 140 <211> 11 <212> PRT <213> Homo sapiens <400> 140 Ala Ile Ser Gly Glu Asn Ala Gly Leu Val Arg 1 5 10 <210> 141 <211> 10 <212> PRT <213> Homo sapiens <400> 141 Glu Val Ala Phe Asp Leu Glu Ile Pro Lys 1 5 10 <210> 142 <211> 18 <212> PRT <213> Homo sapiens <400> 142 Phe Ala His Tyr Val Val Thr Ser Gln Val Val Asn Thr Ala Asn Glu 1 5 10 15 Ala Arg <210> 143 <211> 13 <212> PRT <213> Homo sapiens <400> 143 Gln Tyr Tyr Glu Gly Ser Glu Ile Val Val Ala Gly Arg 1 5 10 <210> 144 <211> 15 <212> PRT <213> Homo sapiens <400> 144 Ala Glu Asp His Phe Ser Val Ile Asp Phe Asn Gln Asn Ile Arg 1 5 10 15 <210> 145 <211> 13 <212> PRT <213> Homo sapiens <400> 145 Ala His Val Ser Phe Lys Pro Thr Val Ala Gln Gln Arg 1 5 10 <210> 146 <211> 20 <212> PRT <213> Homo sapiens <400> 146 Phe Leu His Val Pro Asp Thr Phe Glu Gly His Phe Asp Gly Val Pro 1 5 10 15 Val Ile Ser Lys 20 <210> 147 <211> 11 <212> PRT <213> Homo sapiens <400> 147 Phe Tyr Asn Gln Val Ser Thr Pro Leu Leu Arg 1 5 10 <210> 148 <211> 15 <212> PRT <213> Homo sapiens <400> 148 Ile Gln Pro Ser Gly Gly Thr Asn Ile Asn Glu Ala Leu Leu Arg 1 5 10 15 <210> 149 <211> 10 <212> PRT <213> Homo sapiens <400> 149 Thr Glu Val Asn Val Leu Pro Gly Ala Lys 1 5 10 <210> 150 <211> 11 <212> PRT <213> Homo sapiens <400> 150 Val Gln Phe Glu Leu His Tyr Gln Glu Val Lys 1 5 10 <210> 151 <211> 19 <212> PRT <213> Homo sapiens <400> 151 Val Val Asn Asn Ser Pro Gln Pro Gln Asn Val Val Phe Asp Val Gln 1 5 10 15 Ile Pro Lys <210> 152 <211> 24 <212> PRT <213> Homo sapiens <400> 152 His Arg Gln Gly Pro Val Asn Leu Leu Ser Asp Pro Glu Gln Gly Val 1 5 10 15 Glu Val Thr Gly Gln Tyr Glu Arg 20 <210> 153 <211> 9 <212> PRT <213> Homo sapiens <400> 153 Leu Gly Val Tyr Glu Leu Leu Leu Lys 1 5 <210> 154 <211> 10 <212> PRT <213> Homo sapiens <400> 154 Ala Glu Ala Glu Ser Leu Tyr Gln Ser Lys 1 5 10 <210> 155 <211> 9 <212> PRT <213> Homo sapiens <400> 155 Ala Gln Tyr Glu Asp Ile Ala Gln Lys 1 5 <210> 156 <211> 18 <212> PRT <213> Homo sapiens <400> 156 Glu Gln Ile Lys Ser Leu Asn Asn Gln Phe Ala Ser Phe Ile Asp Lys 1 5 10 15 Val Arg <210> 157 <211> 12 <212> PRT <213> Homo sapiens <400> 157 Phe Leu Glu Gln Gln Asn Gln Val Leu Gln Thr Lys 1 5 10 <210> 158 <211> 24 <212> PRT <213> Homo sapiens <400> 158 Phe Leu Glu Gln Gln Asn Gln Val Leu Gln Thr Lys Trp Glu Leu Leu 1 5 10 15 Gln Gln Val Asp Thr Ser Thr Arg 20 <210> 159 <211> 20 <212> PRT <213> Homo sapiens <400> 159 Phe Ser Ser Cys Gly Gly Gly Gly Gly Ser Phe Gly Ala Gly Gly Gly 1 5 10 15 Phe Gly Ser Arg 20 <210> 160 <211> 31 <212> PRT <213> Homo sapiens <400> 160 Gly Gly Gly Gly Gly Gly Tyr Gly Ser Gly Gly Ser Ser Tyr Gly Ser 1 5 10 15 Gly Gly Gly Ser Tyr Gly Ser Gly Gly Gly Gly Gly Gly Gly Arg 20 25 30 <210> 161 <211> 14 <212> PRT <213> Homo sapiens <400> 161 Gly Ser Gly Gly Gly Ser Ser Gly Gly Ser Ile Gly Gly Arg 1 5 10 <210> 162 <211> 8 <212> PRT <213> Homo sapiens <400> 162 Ile Glu Ile Ser Glu Leu Asn Arg 1 5 <210> 163 <211> 11 <212> PRT <213> Homo sapiens <400> 163 Leu Ala Leu Asp Leu Glu Ile Ala Thr Tyr Arg 1 5 10 <210> 164 <211> 16 <212> PRT <213> Homo sapiens <400> 164 Leu Asp Ser Glu Leu Lys Asn Met Gln Asp Met Val Glu Asp Tyr Arg 1 5 10 15 <210> 165 <211> 12 <212> PRT <213> Homo sapiens <400> 165 Leu Leu Arg Asp Tyr Gln Glu Leu Met Asn Thr Lys 1 5 10 <210> 166 <211> 12 <212> PRT <213> Homo sapiens <400> 166 Leu Asn Asp Leu Glu Asp Ala Leu Gln Gln Ala Lys 1 5 10 <210> 167 <211> 10 <212> PRT <213> Homo sapiens <400> 167 Leu Arg Ser Glu Ile Asp Asn Val Lys Lys 1 5 10 <210> 168 <211> 14 <212> PRT <213> Homo sapiens <400> 168 Asn Lys Leu Asn Asp Leu Glu Asp Ala Leu Gln Gln Ala Lys 1 5 10 <210> 169 <211> 19 <212> PRT <213> Homo sapiens <400> 169 Asn Lys Leu Asn Asp Leu Glu Asp Ala Leu Gln Gln Ala Lys Glu Asp 1 5 10 15 Leu Ala Arg <210> 170 <211> 10 <212> PRT <213> Homo sapiens <400> 170 Asn Lys Tyr Glu Asp Glu Ile Asn Lys Arg 1 5 10 <210> 171 <211> 15 <212> PRT <213> Homo sapiens <400> 171 Asn Ser Lys Ile Glu Ile Ser Glu Leu Asn Arg Val Ile Gln Arg 1 5 10 15 <210> 172 <211> 15 <212> PRT <213> Homo sapiens <400> 172 Gln Ile Ser Asn Leu Gln Gln Ser Ile Ser Asp Ala Glu Gln Arg 1 5 10 15 <210> 173 <211> 23 <212> PRT <213> Homo sapiens <400> 173 Ser Glu Ile Asp Asn Val Lys Lys Gln Ile Ser Asn Leu Gln Gln Ser 1 5 10 15 Ile Ser Asp Ala Glu Gln Arg 20 <210> 174 <211> 17 <212> PRT <213> Homo sapiens <400> 174 Ser Gly Gly Gly Phe Ser Ser Gly Ser Ala Gly Ile Ile Asn Tyr Gln 1 5 10 15 Arg <210> 175 <211> 18 <212> PRT <213> Homo sapiens <400> 175 Ser Gly Gly Gly Phe Ser Ser Gly Ser Ala Gly Ile Ile Asn Tyr Gln 1 5 10 15 Arg Arg <210> 176 <211> 27 <212> PRT <213> Homo sapiens <400> 176 Ser Gly Gly Gly Gly Gly Arg Phe Ser Ser Cys Gly Gly Gly Gly Gly 1 5 10 15 Ser Phe Gly Ala Gly Gly Gly Phe Gly Ser Arg 20 25 <210> 177 <211> 21 <212> PRT <213> Homo sapiens <400> 177 Ser Gly Tyr Arg Ser Gly Gly Gly Phe Ser Ser Gly Ser Ala Gly Ile 1 5 10 15 Ile Asn Tyr Gln Arg 20 <210> 178 <211> 8 <212> PRT <213> Homo sapiens <400> 178 Ser Ile Ser Ile Ser Val Ala Arg 1 5 <210> 179 <211> 12 <212> PRT <213> Homo sapiens <400> 179 Ser Lys Ala Glu Ala Glu Ser Leu Tyr Gln Ser Lys 1 5 10 <210> 180 <211> 22 <212> PRT <213> Homo sapiens <400> 180 Ser Lys Ala Glu Ala Glu Ser Leu Tyr Gln Ser Lys Tyr Glu Glu Leu 1 5 10 15 Gln Ile Thr Ala Gly Arg 20 <210> 181 <211> 12 <212> PRT <213> Homo sapiens <400> 181 Ser Leu Asp Leu Asp Ser Ile Ile Ala Glu Val Lys 1 5 10 <210> 182 <211> 12 <212> PRT <213> Homo sapiens <400> 182 Ser Leu Asn Asn Gln Phe Ala Ser Phe Ile Asp Lys 1 5 10 <210> 183 <211> 14 <212> PRT <213> Homo sapiens <400> 183 Ser Leu Asn Asn Gln Phe Ala Ser Phe Ile Asp Lys Val Arg 1 5 10 <210> 184 <211> 8 <212> PRT <213> Homo sapiens <400> 184 Leu Val Asn Leu Gly Gly Ser Lys 1 5 <210> 185 <211> 17 <212> PRT <213> Homo sapiens <400> 185 Ser Leu Val Asn Leu Gly Gly Ser Lys Ser Ile Ser Ile Ser Val Ala 1 5 10 15 Arg <210> 186 <211> 16 <212> PRT <213> Homo sapiens <400> 186 Thr His Asn Leu Glu Pro Tyr Phe Glu Ser Phe Ile Asn Asn Leu Arg 1 5 10 15 <210> 187 <211> 17 <212> PRT <213> Homo sapiens <400> 187 Thr His Asn Leu Glu Pro Tyr Phe Glu Ser Phe Ile Asn Asn Leu Arg 1 5 10 15 Arg <210> 188 <211> 9 <212> PRT <213> Homo sapiens <400> 188 Thr Leu Leu Glu Gly Glu Glu Ser Arg 1 5 <210> 189 <211> 11 <212> PRT <213> Homo sapiens <400> 189 Thr Asn Ala Glu Asn Glu Phe Val Thr Ile Lys 1 5 10 <210> 190 <211> 12 <212> PRT <213> Homo sapiens <400> 190 Thr Asn Ala Glu Asn Glu Phe Val Thr Ile Lys Lys 1 5 10 <210> 191 <211> 12 <212> PRT <213> Homo sapiens <400> 191 Trp Glu Leu Leu Gln Gln Val Asp Thr Ser Thr Arg 1 5 10 <210> 192 <211> 10 <212> PRT <213> Homo sapiens <400> 192 Tyr Glu Glu Leu Gln Ile Thr Ala Gly Arg 1 5 10 <210> 193 <211> 16 <212> PRT <213> Homo sapiens <400> 193 Tyr Glu Glu Leu Gln Ile Thr Ala Gly Arg His Gly Asp Ser Val Arg 1 5 10 15 <210> 194 <211> 20 <212> PRT <213> Homo sapiens <400> 194 Ala Glu Ala Glu Ser Leu Tyr Gln Ser Lys Tyr Glu Glu Leu Gln Ile 1 5 10 15 Thr Ala Gly Arg 20 <210> 195 <211> 13 <212> PRT <213> Homo sapiens <400> 195 Ala Gly Lys Gly Met His Gly Gly Val Pro Gly Gly Lys 1 5 10 <210> 196 <211> 10 <212> PRT <213> Homo sapiens <400> 196 Gly Met His Gly Gly Val Pro Gly Gly Lys 1 5 10 <210> 197 <211> 7 <212> PRT <213> Homo sapiens <400> 197 Gln Glu Leu Asn Pro Leu Lys 1 5 <210> 198 <211> 10 <212> PRT <213> Homo sapiens <400> 198 Gln Phe Ile Glu Ser Glu Cys Ile Pro Arg 1 5 10 <210> 199 <211> 13 <212> PRT <213> Homo sapiens <400> 199 Ala Gly Lys Gly Met His Gly Gly Val Pro Gly Gly Lys 1 5 10 <210> 200 <211> 25 <212> PRT <213> Homo sapiens <400> 200 Ala Gly Lys Gly Met His Gly Gly Val Pro Gly Gly Lys Gln Phe Ile 1 5 10 15 Glu Asn Gly Ser Glu Phe Ala Gln Lys 20 25 <210> 201 <211> 8 <212> PRT <213> Homo sapiens <400> 201 Phe Ser Leu Leu Lys Pro Trp Ala 1 5 <210> 202 <211> 10 <212> PRT <213> Homo sapiens <400> 202 Gly Met His Gly Gly Val Pro Gly Gly Lys 1 5 10 <210> 203 <211> 22 <212> PRT <213> Homo sapiens <400> 203 Gly Met His Gly Gly Val Pro Gly Gly Lys Gln Phe Ile Glu Asn Gly 1 5 10 15 Ser Glu Phe Ala Gln Lys 20 <210> 204 <211> 25 <212> PRT <213> Homo sapiens <400> 204 Gly Met His Gly Gly Val Pro Gly Gly Lys Gln Phe Ile Glu Asn Gly 1 5 10 15 Ser Glu Phe Ala Gln Lys Leu Leu Lys 20 25 <210> 205 <211> 9 <212> PRT <213> Homo sapiens <400> 205 Lys Phe Ser Leu Leu Lys Pro Trp Ala 1 5 <210> 206 <211> 7 <212> PRT <213> Homo sapiens <400> 206 Gln Glu Leu Asn Pro Leu Lys 1 5 <210> 207 <211> 12 <212> PRT <213> Homo sapiens <400> 207 Gln Glu Leu Asn Pro Leu Lys Ser Ile Val Glu Lys 1 5 10 <210> 208 <211> 12 <212> PRT <213> Homo sapiens <400> 208 Gln Phe Ile Glu Asn Gly Ser Glu Phe Ala Gln Lys 1 5 10 <210> 209 <211> 15 <212> PRT <213> Homo sapiens <400> 209 Gln Phe Ile Glu Asn Gly Ser Glu Phe Ala Gln Lys Leu Leu Lys 1 5 10 15 <210> 210 <211> 16 <212> PRT <213> Homo sapiens <400> 210 Gln Phe Ile Glu Asn Gly Ser Glu Phe Ala Gln Lys Leu Leu Lys Lys 1 5 10 15 <210> 211 <211> 11 <212> PRT <213> Homo sapiens <400> 211 Ser Ile Leu Leu Thr Glu Gln Ala Leu Ala Lys 1 5 10 <210> 212 <211> 14 <212> PRT <213> Homo sapiens <400> 212 Ser Ile Leu Leu Thr Glu Gln Ala Leu Ala Lys Ala Gly Lys 1 5 10 <210> 213 <211> 16 <212> PRT <213> Homo sapiens <400> 213 Ser Ile Val Glu Lys Ser Ile Leu Leu Thr Glu Gln Ala Leu Ala Lys 1 5 10 15 <210> 214 <211> 19 <212> PRT <213> Homo sapiens <400> 214 Ser Ile Val Glu Lys Ser Ile Leu Leu Thr Glu Gln Ala Leu Ala Lys 1 5 10 15 Ala Gly Lys <210> 215 <211> 29 <212> PRT <213> Homo sapiens <400> 215 Asp Ile Glu Asn Gln Tyr Glu Thr Gln Ile Thr Gln Ile Glu His Glu 1 5 10 15 Val Ser Ser Ser Gly Gln Glu Val Gln Ser Ser Ala Lys 20 25 <210> 216 <211> 23 <212> PRT <213> Homo sapiens <400> 216 Glu Ile Glu Thr Tyr His Asn Leu Leu Glu Gly Gly Gln Glu Asp Phe 1 5 10 15 Glu Ser Ser Gly Ala Gly Lys 20 <210> 217 <211> 25 <212> PRT <213> Homo sapiens <400> 217 Phe Ser Ser Ser Gly Gly Gly Gly Gly Gly Gly Arg Phe Ser Ser Ser 1 5 10 15 Ser Gly Tyr Gly Gly Gly Ser Ser Arg 20 25 <210> 218 <211> 13 <212> PRT <213> Homo sapiens <400> 218 Phe Ser Ser Ser Ser Gly Tyr Gly Gly Gly Ser Ser Arg 1 5 10 <210> 219 <211> 32 <212> PRT <213> Homo sapiens <400> 219 Gly Gly Gly Gly Ser Phe Gly Tyr Ser Tyr Gly Gly Gly Ser Gly Gly 1 5 10 15 Gly Phe Ser Ala Ser Ser Leu Gly Gly Gly Phe Gly Gly Gly Ser Arg 20 25 30 <210> 220 <211> 23 <212> PRT <213> Homo sapiens <400> 220 Gly Gly Ser Gly Gly Ser Tyr Gly Gly Gly Gly Ser Gly Gly Gly Tyr 1 5 10 15 Gly Gly Gly Ser Gly Ser Arg 20 <210> 221 <211> 16 <212> PRT <213> Homo sapiens <400> 221 His Gly Val Gln Glu Leu Glu Ile Glu Leu Gln Ser Gln Leu Ser Lys 1 5 10 15 <210> 222 <211> 17 <212> PRT <213> Homo sapiens <400> 222 His Gly Val Gln Glu Leu Glu Ile Glu Leu Gln Ser Gln Leu Ser Lys 1 5 10 15 Lys <210> 223 <211> 7 <212> PRT <213> Homo sapiens <400> 223 Leu Ala Ser Tyr Leu Asp Lys 1 5 <210> 224 <211> 21 <212> PRT <213> Homo sapiens <400> 224 Leu Ala Ser Tyr Leu Asp Lys Val Gln Ala Leu Glu Glu Ala Asn Asn 1 5 10 15 Asp Leu Glu Asn Lys 20 <210> 225 <211> 26 <212> PRT <213> Homo sapiens <400> 225 Leu Glu Lys Glu Ile Glu Thr Tyr His Asn Leu Leu Glu Gly Gly Gln 1 5 10 15 Glu Asp Phe Glu Ser Ser Gly Ala Gly Lys 20 25 <210> 226 <211> 32 <212> PRT <213> Homo sapiens <400> 226 Asn Arg Lys Asp Ile Glu Asn Gln Tyr Glu Thr Gln Ile Thr Gln Ile 1 5 10 15 Glu His Glu Val Ser Ser Ser Gly Gln Glu Val Gln Ser Ser Ala Lys 20 25 30 <210> 227 <211> 9 <212> PRT <213> Homo sapiens <400> 227 Gln Glu Tyr Glu Gln Leu Ile Ala Lys 1 5 <210> 228 <211> 11 <212> PRT <213> Homo sapiens <400> 228 Gln Gly Val Asp Ala Asp Ile Asn Gly Leu Arg 1 5 10 <210> 229 <211> 10 <212> PRT <213> Homo sapiens <400> 229 Gln Val Leu Asp Asn Leu Thr Met Glu Lys 1 5 10 <210> 230 <211> 12 <212> PRT <213> Homo sapiens <400> 230 Ser Cys Arg Gln Phe Ser Ser Ser Tyr Leu Ser Arg 1 5 10 <210> 231 <211> 16 <212> PRT <213> Homo sapiens <400> 231 Ser Gly Gly Gly Gly Gly Gly Gly Leu Gly Ser Gly Gly Ser Ile Arg 1 5 10 15 <210> 232 <211> 9 <212> PRT <213> Homo sapiens <400> 232 Ser Thr Met Gln Glu Leu Asn Ser Arg 1 5 <210> 233 <211> 9 <212> PRT <213> Homo sapiens <400> 233 Thr Leu Leu Asp Ile Asp Asn Thr Arg 1 5 <210> 234 <211> 15 <212> PRT <213> Homo sapiens <400> 234 Thr Leu Asn Asp Met Arg Gln Glu Tyr Glu Gln Leu Ile Ala Lys 1 5 10 15 <210> 235 <211> 14 <212> PRT <213> Homo sapiens <400> 235 Val Gln Ala Leu Glu Glu Ala Asn Asn Asp Leu Glu Asn Lys 1 5 10 <210> 236 <211> 10 <212> PRT <213> Homo sapiens <400> 236 Asp Leu Leu Leu Pro Gln Pro Asp Leu Arg 1 5 10 <210> 237 <211> 7 <212> PRT <213> Homo sapiens <400> 237 Gly Pro Leu Gln Leu Glu Arg 1 5 <210> 238 <211> 10 <212> PRT <213> Homo sapiens <400> 238 Val Ala Ala Gly Ala Phe Gln Gly Leu Arg 1 5 10 <210> 239 <211> 13 <212> PRT <213> Homo sapiens <400> 239 Ala Thr Leu Lys Asp Gln Leu Ile Tyr Asn Leu Leu Lys 1 5 10 <210> 240 <211> 21 <212> PRT <213> Homo sapiens <400> 240 Ala Thr Leu Lys Asp Gln Leu Ile Tyr Asn Leu Leu Lys Glu Glu Gln 1 5 10 15 Thr Pro Gln Asn Lys 20 <210> 241 <211> 15 <212> PRT <213> Homo sapiens <400> 241 Asp Leu Ala Asp Glu Leu Ala Leu Val Asp Val Ile Glu Asp Lys 1 5 10 15 <210> 242 <211> 9 <212> PRT <213> Homo sapiens <400> 242 Asp Gln Leu Ile Tyr Asn Leu Leu Lys 1 5 <210> 243 <211> 17 <212> PRT <213> Homo sapiens <400> 243 Asp Gln Leu Ile Tyr Asn Leu Leu Lys Glu Glu Gln Thr Pro Gln Asn 1 5 10 15 Lys <210> 244 <211> 9 <212> PRT <213> Homo sapiens <400> 244 Leu Val Ile Ile Thr Ala Gly Ala Arg 1 5 <210> 245 <211> 14 <212> PRT <213> Homo sapiens <400> 245 Asn Arg Val Ile Gly Ser Gly Cys Asn Leu Asp Ser Ala Arg 1 5 10 <210> 246 <211> 14 <212> PRT <213> Homo sapiens <400> 246 Asn Val Asn Ile Phe Lys Phe Ile Ile Pro Asn Val Val Lys 1 5 10 <210> 247 <211> 11 <212> PRT <213> Homo sapiens <400> 247 Gln Val Val Glu Ser Ala Tyr Glu Val Ile Lys 1 5 10 <210> 248 <211> 10 <212> PRT <213> Homo sapiens <400> 248 Ser Ala Asp Thr Leu Trp Gly Ile Gln Lys 1 5 10 <210> 249 <211> 16 <212> PRT <213> Homo sapiens <400> 249 Thr Leu His Pro Asp Leu Gly Thr Asp Lys Asp Lys Glu Gln Trp Lys 1 5 10 15 <210> 250 <211> 12 <212> PRT <213> Homo sapiens <400> 250 Val Ile Gly Ser Gly Cys Asn Leu Asp Ser Ala Arg 1 5 10 <210> 251 <211> 10 <212> PRT <213> Homo sapiens <400> 251 Val Thr Leu Thr Ser Glu Glu Glu Ala Arg 1 5 10 <210> 252 <211> 14 <212> PRT <213> Homo sapiens <400> 252 Ile Val Ala Asp Lys Asp Tyr Ser Val Thr Ala Asn Ser Lys 1 5 10 <210> 253 <211> 16 <212> PRT <213> Homo sapiens <400> 253 Leu Ile Ala Pro Val Ala Glu Glu Glu Ala Thr Val Pro Asn Asn Lys 1 5 10 15 <210> 254 <211> 10 <212> PRT <213> Homo sapiens <400> 254 Ser Ala Asp Thr Leu Trp Asp Ile Gln Lys 1 5 10 <210> 255 <211> 15 <212> PRT <213> Homo sapiens <400> 255 Ser Leu Ala Asp Glu Leu Ala Leu Val Asp Val Leu Glu Asp Lys 1 5 10 15 <210> 256 <211> 12 <212> PRT <213> Homo sapiens <400> 256 Val Ile Gly Ser Gly Cys Asn Leu Asp Ser Ala Arg 1 5 10 <210> 257 <211> 12 <212> PRT <213> Homo sapiens <400> 257 Ala Glu Ala Ser Ser Asp Pro Gly Ala Glu Glu Arg 1 5 10 <210> 258 <211> 20 <212> PRT <213> Homo sapiens <400> 258 Asp Arg Gln Leu Gln Ala Gln Asp Glu Glu Gly Gly Gly His Val Pro 1 5 10 15 Glu Arg Pro Lys 20 <210> 259 <211> 27 <212> PRT <213> Homo sapiens <400> 259 Glu Gly Pro Gly Pro Glu Asp Thr Val Gln Asp Asn Leu Gly Ala Ala 1 5 10 15 Gly Ala Glu Glu Glu Gln Glu Glu His Gln Lys 20 25 <210> 260 <211> 13 <212> PRT <213> Homo sapiens <400> 260 Trp Glu Thr Gly Glu Val Gln Ala Gln Ser Ala Ala Lys 1 5 10 <210> 261 <211> 17 <212> PRT <213> Homo sapiens <400> 261 Ser Gln Glu Thr Glu Cys Thr Tyr Phe Ser Thr Pro Leu Leu Leu Gly 1 5 10 15 Lys <210> 262 <211> 19 <212> PRT <213> Homo sapiens <400> 262 Val Ala Val Leu Gly Ala Ser Gly Gly Ile Gly Gln Pro Leu Ser Leu 1 5 10 15 Leu Leu Lys <210> 263 <211> 12 <212> PRT <213> Homo sapiens <400> 263 Ala Leu Gly Gly Leu Ala Cys Asp Leu Pro Gly Arg 1 5 10 <210> 264 <211> 24 <212> PRT <213> Homo sapiens <400> 264 Ala Leu Gly Gly Leu Ala Cys Asp Leu Pro Gly Arg Phe Val Ala Glu 1 5 10 15 Ser Ala Glu Val Leu Leu Pro Arg 20 <210> 265 <211> 10 <212> PRT <213> Homo sapiens <400> 265 Glu Ile Asp Glu Ser Leu Ile Phe Tyr Lys 1 5 10 <210> 266 <211> 12 <212> PRT <213> Homo sapiens <400> 266 Phe Val Ala Glu Ser Ala Glu Val Leu Leu Pro Arg 1 5 10 <210> 267 <211> 12 <212> PRT <213> Homo sapiens <400> 267 Gly Leu Leu Pro Val Leu Gly Gln Pro Ile Ile Arg 1 5 10 <210> 268 <211> 10 <212> PRT <213> Homo sapiens <400> 268 Gly Ser Leu Leu Ser Glu Ala Asp Val Arg 1 5 10 <210> 269 <211> 14 <212> PRT <213> Homo sapiens <400> 269 Ile Gln Ser Phe Leu Gly Gly Ala Pro Thr Glu Asp Leu Lys 1 5 10 <210> 270 <211> 11 <212> PRT <213> Homo sapiens <400> 270 Ile Thr Lys Ala Asn Val Asp Leu Leu Pro Arg 1 5 10 <210> 271 <211> 10 <212> PRT <213> Homo sapiens <400> 271 Leu Leu Gly Pro His Val Glu Gly Leu Lys 1 5 10 <210> 272 <211> 14 <212> PRT <213> Homo sapiens <400> 272 Leu Leu Gly Pro His Val Glu Gly Leu Lys Ala Glu Glu Arg 1 5 10 <210> 273 <211> 12 <212> PRT <213> Homo sapiens <400> 273 Leu Leu Pro Ala Ala Leu Ala Cys Trp Gly Val Arg 1 5 10 <210> 274 <211> 16 <212> PRT <213> Homo sapiens <400> 274 Leu Arg Thr Asp Ala Val Leu Pro Leu Thr Val Ala Glu Val Gln Lys 1 5 10 15 <210> 275 <211> 17 <212> PRT <213> Homo sapiens <400> 275 Leu Val Ser Cys Pro Gly Pro Leu Asp Gln Asp Gln Gln Glu Ala Ala 1 5 10 15 Arg <210> 276 <211> 8 <212> PRT <213> Homo sapiens <400> 276 Gln Leu Asp Val Leu Tyr Pro Lys 1 5 <210> 277 <211> 17 <212> PRT <213> Homo sapiens <400> 277 Gln Leu Leu Gly Phe Pro Cys Ala Glu Val Ser Gly Leu Ser Thr Glu 1 5 10 15 Arg <210> 278 <211> 14 <212> PRT <213> Homo sapiens <400> 278 Thr Asp Ala Val Leu Pro Leu Thr Val Ala Glu Val Gln Lys 1 5 10 <210> 279 <211> 15 <212> PRT <213> Homo sapiens <400> 279 Val Asn Ala Ile Pro Phe Thr Tyr Glu Gln Leu Asp Val Leu Lys 1 5 10 15 <210> 280 <211> 18 <212> PRT <213> Homo sapiens <400> 280 His Leu Ala Cys Leu Pro Arg Glu Pro Gly Leu Cys Thr Trp Gln Ser 1 5 10 15 Leu Arg <210> 281 <211> 25 <212> PRT <213> Homo sapiens <400> 281 Leu Gln Asp Gly Leu Leu His Ile Thr Thr Cys Ser Phe Val Ala Pro 1 5 10 15 Trp Asn Ser Leu Ser Leu Ala Gln Arg 20 25 <210> 282 <211> 19 <212> PRT <213> Homo sapiens <400> 282 Leu Gln Ser Gly Thr His Cys Leu Trp Thr Asp Gln Leu Leu Gln Gly 1 5 10 15 Ser Glu Lys <210> 283 <211> 20 <212> PRT <213> Homo sapiens <400> 283 Thr Tyr Thr Val Gly Cys Glu Glu Cys Thr Val Phe Pro Cys Leu Ser 1 5 10 15 Ile Pro Cys Lys 20 <210> 284 <211> 9 <212> PRT <213> Homo sapiens <400> 284 Trp Val Gly Asp Leu Pro Asn Gly Arg 1 5 <210> 285 <211> 12 <212> PRT <213> Homo sapiens <400> 285 Trp Val Gly Asp Leu Pro Asn Gly Arg Val Cys Pro 1 5 10 <210> 286 <211> 11 <212> PRT <213> Homo sapiens <400> 286 Phe Thr Asp Glu Glu Val Asp Glu Leu Tyr Arg 1 5 10 <210> 287 <211> 10 <212> PRT <213> Homo sapiens <400> 287 Gly Asn Phe Asn Tyr Ile Glu Phe Thr Arg 1 5 10 <210> 288 <211> 11 <212> PRT <213> Homo sapiens <400> 288 Leu Asn Gly Thr Asp Pro Glu Asp Val Ile Arg 1 5 10 <210> 289 <211> 17 <212> PRT <213> Homo sapiens <400> 289 Glu Ala Leu Ala Glu Ala Ala Leu Glu Ser Pro Arg Pro Ala Leu Val 1 5 10 15 Arg <210> 290 <211> 31 <212> PRT <213> Homo sapiens <400> 290 Glu Glu Leu Leu Arg Ala Gln Glu Ala Pro Gly Gln Ala Glu Pro Pro 1 5 10 15 Ala Ala Ala Glu Val Gln Gly Ala Gly Asn Glu Asn Glu Pro Arg 20 25 30 <210> 291 <211> 14 <212> PRT <213> Homo sapiens <400> 291 Leu Leu Val Val Asp Pro Glu Thr Asp Glu Gln Leu Gln Lys 1 5 10 <210> 292 <211> 10 <212> PRT <213> Homo sapiens <400> 292 Leu Val Glu Pro Gly Ser Pro Ala Glu Lys 1 5 10 <210> 293 <211> 14 <212> PRT <213> Homo sapiens <400> 293 Ser Val Asp Pro Asp Ser Pro Ala Glu Ala Ser Gly Leu Arg 1 5 10 <210> 294 <211> 23 <212> PRT <213> Homo sapiens <400> 294 Gly Ser Gln Thr Gln Ser His Pro Asp Leu Gly Thr Glu Gly Cys Trp 1 5 10 15 Asp Gln Leu Ser Ala Pro Arg 20 <210> 295 <211> 13 <212> PRT <213> Homo sapiens <400> 295 Thr Asp Cys Pro Gly Asp Ala Leu Phe Asp Leu Leu Arg 1 5 10 <210> 296 <211> 9 <212> PRT <213> Homo sapiens <400> 296 Ala Ala Glu Gln Asp Pro Glu Ala Arg 1 5 <210> 297 <211> 14 <212> PRT <213> Homo sapiens <400> 297 Leu Gln Ala Leu Val Asn Ser Leu Cys Ala Gly Gln Ser Pro 1 5 10 <210> 298 <211> 14 <212> PRT <213> Homo sapiens <400> 298 Leu Arg Ser Pro Ala Gln Tyr Gln Val Val Leu Ser Glu Arg 1 5 10 <210> 299 <211> 12 <212> PRT <213> Homo sapiens <400> 299 Asp Ser Pro Ser Val Trp Ala Ala Val Pro Gly Lys 1 5 10 <210> 300 <211> 11 <212> PRT <213> Homo sapiens <400> 300 Glu Gly Val His Gly Gly Leu Ile Asn Lys Lys 1 5 10 <210> 301 <211> 14 <212> PRT <213> Homo sapiens <400> 301 Ser Ser Phe Tyr Val Asn Gly Leu Thr Leu Gly Gly Gln Lys 1 5 10 <210> 302 <211> 19 <212> PRT <213> Homo sapiens <400> 302 Ser Ser Phe Tyr Val Asn Gly Leu Thr Leu Gly Gly Gln Lys Cys Ser 1 5 10 15 Val Ile Arg <210> 303 <211> 14 <212> PRT <213> Homo sapiens <400> 303 Ser Thr Gly Gly Ala Pro Thr Phe Asn Val Thr Val Thr Lys 1 5 10 <210> 304 <211> 17 <212> PRT <213> Homo sapiens <400> 304 Ser Thr Gly Gly Ala Pro Thr Phe Asn Val Thr Val Thr Lys Thr Asp 1 5 10 15 Lys <210> 305 <211> 16 <212> PRT <213> Homo sapiens <400> 305 Thr Phe Val Asn Ile Thr Pro Ala Glu Val Gly Val Leu Val Gly Lys 1 5 10 15 <210> 306 <211> 18 <212> PRT <213> Homo sapiens <400> 306 Thr Phe Val Asn Ile Thr Pro Ala Glu Val Gly Val Leu Val Gly Lys 1 5 10 15 Asp Arg <210> 307 <211> 16 <212> PRT <213> Homo sapiens <400> 307 Thr Lys Ser Thr Gly Gly Ala Pro Thr Phe Asn Val Thr Val Thr Lys 1 5 10 15 <210> 308 <211> 19 <212> PRT <213> Homo sapiens <400> 308 Thr Lys Ser Thr Gly Gly Ala Pro Thr Phe Asn Val Thr Val Thr Lys 1 5 10 15 Thr Asp Lys <210> 309 <211> 10 <212> PRT <213> Homo sapiens <400> 309 Ala Thr Phe Ile Ser Val Gln Leu Lys Lys 1 5 10 <210> 310 <211> 11 <212> PRT <213> Homo sapiens <400> 310 Phe Tyr Asn Glu Leu Thr Glu Ile Leu Val Arg 1 5 10 <210> 311 <211> 14 <212> PRT <213> Homo sapiens <400> 311 Leu Ala Asn Gln Ala Ala Asp Tyr Phe Gly Asp Ala Phe Lys 1 5 10 <210> 312 <211> 13 <212> PRT <213> Homo sapiens <400> 312 Leu Leu Asp Glu Glu Glu Ala Thr Asp Asn Asp Leu Arg 1 5 10 <210> 313 <211> 16 <212> PRT <213> Homo sapiens <400> 313 Ser Val Ile Glu Gln Gly Gly Ile Gln Thr Val Asp Gln Leu Ile Lys 1 5 10 15 <210> 314 <211> 26 <212> PRT <213> Homo sapiens <400> 314 Cys Ile Trp Gly Pro Ser Tyr Trp Cys Gln Asn Thr Glu Thr Ala Ala 1 5 10 15 Gln Cys Asn Ala Val Glu His Cys Lys Arg 20 25 <210> 315 <211> 15 <212> PRT <213> Homo sapiens <400> 315 Glu Ile Val Asp Ser Tyr Leu Pro Val Ile Leu Asp Ile Ile Lys 1 5 10 15 <210> 316 <211> 10 <212> PRT <213> Homo sapiens <400> 316 Gly Ser Ala Val Trp Cys Gln Asn Val Lys 1 5 10 <210> 317 <211> 13 <212> PRT <213> Homo sapiens <400> 317 His Cys Leu Gln Thr Val Trp Asn Lys Pro Thr Val Lys 1 5 10 <210> 318 <211> 9 <212> PRT <213> Homo sapiens <400> 318 His Leu Ala Glu Leu Asn His Gln Lys 1 5 <210> 319 <211> 12 <212> PRT <213> Homo sapiens <400> 319 Ala Phe Ile Gln Leu Trp Ala Phe Asp Ala Val Lys 1 5 10 <210> 320 <211> 14 <212> PRT <213> Homo sapiens <400> 320 Ala Phe Ile Gln Leu Trp Ala Phe Asp Ala Val Lys Gly Lys 1 5 10 <210> 321 <211> 15 <212> PRT <213> Homo sapiens <400> 321 Cys Val Leu Phe Pro Tyr Gly Gly Cys Gln Gly Asn Gly Asn Lys 1 5 10 15 <210> 322 <211> 15 <212> PRT <213> Homo sapiens <400> 322 Thr Val Ala Ala Cys Asn Leu Pro Ile Val Arg Gly Pro Cys Arg 1 5 10 15 <210> 323 <211> 8 <212> PRT <213> Homo sapiens <400> 323 Glu Thr Leu Leu Gln Asp Phe Arg 1 5 <210> 324 <211> 15 <212> PRT <213> Homo sapiens <400> 324 Glu Tyr Cys Gly Val Pro Gly Asp Gly Asp Glu Glu Leu Leu Arg 1 5 10 15 <210> 325 <211> 11 <212> PRT <213> Homo sapiens <400> 325 Thr Val Ala Ala Cys Asn Leu Pro Ile Val Arg 1 5 10 <210> 326 <211> 20 <212> PRT <213> Homo sapiens <400> 326 Asp Lys Leu Ala Ala Cys Leu Glu Gly Asn Cys Ala Glu Gly Leu Gly 1 5 10 15 Thr Asn Tyr Arg 20 <210> 327 <211> 10 <212> PRT <213> Homo sapiens <400> 327 Glu Leu Leu Glu Ser Tyr Ile Asp Gly Arg 1 5 10 <210> 328 <211> 16 <212> PRT <213> Homo sapiens <400> 328 Lys Ser Pro Gln Glu Leu Leu Cys Gly Ala Ser Leu Ile Ser Asp Arg 1 5 10 15 <210> 329 <211> 19 <212> PRT <213> Homo sapiens <400> 329 Leu Ala Val Thr Thr His Gly Leu Pro Cys Leu Ala Trp Ala Ser Ala 1 5 10 15 Gln Ala Lys <210> 330 <211> 9 <212> PRT <213> Homo sapiens <400> 330 Ser Gly Ile Glu Cys Gln Leu Trp Arg 1 5 <210> 331 <211> 13 <212> PRT <213> Homo sapiens <400> 331 Thr Ala Thr Ser Glu Tyr Gln Thr Phe Phe Asn Pro Arg 1 5 10 <210> 332 <211> 26 <212> PRT <213> Homo sapiens <400> 332 Ser Glu Gly Ser Ser Val Asn Leu Ser Pro Pro Leu Glu Gln Cys Val 1 5 10 15 Pro Asp Arg Gly Gln Gln Tyr Gln Gly Arg 20 25 <210> 333 <211> 15 <212> PRT <213> Homo sapiens <400> 333 Ala Asn Asn Thr Phe Tyr Gly Leu Ser Ala Gly Val Phe Thr Lys 1 5 10 15 <210> 334 <211> 14 <212> PRT <213> Homo sapiens <400> 334 Glu Leu Gly Glu Tyr Gly Phe His Glu Tyr Thr Glu Val Lys 1 5 10 <210> 335 <211> 10 <212> PRT <213> Homo sapiens <400> 335 Phe Lys Ser Leu Asp Asp Val Ile Lys Arg 1 5 10 <210> 336 <211> 17 <212> PRT <213> Homo sapiens <400> 336 Gly Tyr Phe Val Gln Pro Thr Val Phe Ser Asn Val Thr Asp Glu Met 1 5 10 15 Arg <210> 337 <211> 14 <212> PRT <213> Homo sapiens <400> 337 Ile Phe Ile Asn Asn Glu Trp His Asp Ser Val Ser Gly Lys 1 5 10 <210> 338 <211> 13 <212> PRT <213> Homo sapiens <400> 338 Ile Phe Val Glu Glu Ser Ile Tyr Asp Glu Phe Val Arg 1 5 10 <210> 339 <211> 14 <212> PRT <213> Homo sapiens <400> 339 Ile Phe Val Glu Glu Ser Ile Tyr Asp Glu Phe Val Arg Arg 1 5 10 <210> 340 <211> 31 <212> PRT <213> Homo sapiens <400> 340 Ile Gly Pro Ala Leu Ser Cys Gly Asn Thr Val Val Val Lys Pro Ala 1 5 10 15 Glu Gln Thr Pro Leu Thr Ala Leu His Val Ala Ser Leu Ile Lys 20 25 30 <210> 341 <211> 10 <212> PRT <213> Homo sapiens <400> 341 Ile Leu Asp Leu Ile Glu Ser Gly Lys Lys 1 5 10 <210> 342 <211> 26 <212> PRT <213> Homo sapiens <400> 342 Lys Phe Pro Val Phe Asn Pro Ala Thr Glu Glu Glu Leu Cys Gln Val 1 5 10 15 Glu Glu Gly Asp Lys Glu Asp Val Asp Lys 20 25 <210> 343 <211> 25 <212> PRT <213> Homo sapiens <400> 343 Lys Tyr Ile Leu Gly Asn Pro Leu Thr Pro Gly Val Thr Gln Gly Pro 1 5 10 15 Gln Ile Asp Lys Glu Gln Tyr Asp Lys 20 25 <210> 344 <211> 7 <212> PRT <213> Homo sapiens <400> 344 Leu Ala Asp Leu Ile Glu Arg 1 5 <210> 345 <211> 11 <212> PRT <213> Homo sapiens <400> 345 Leu Glu Cys Gly Gly Gly Pro Trp Gly Asn Lys 1 5 10 <210> 346 <211> 11 <212> PRT <213> Homo sapiens <400> 346 Leu Leu Tyr Lys Leu Ala Asp Leu Ile Glu Arg 1 5 10 <210> 347 <211> 15 <212> PRT <213> Homo sapiens <400> 347 Leu Tyr Ser Asn Ala Tyr Leu Asn Asp Leu Ala Gly Cys Ile Lys 1 5 10 15 <210> 348 <211> 16 <212> PRT <213> Homo sapiens <400> 348 Arg Ala Asn Asn Thr Phe Tyr Gly Leu Ser Ala Gly Val Phe Thr Lys 1 5 10 15 <210> 349 <211> 23 <212> PRT <213> Homo sapiens <400> 349 Ser Leu Asp Asp Val Ile Lys Arg Ala Asn Asn Thr Phe Tyr Gly Leu 1 5 10 15 Ser Ala Gly Val Phe Thr Lys 20 <210> 350 <211> 16 <212> PRT <213> Homo sapiens <400> 350 Ser Ser Ser Gly Thr Pro Asp Leu Pro Val Leu Leu Thr Asp Leu Lys 1 5 10 15 <210> 351 <211> 13 <212> PRT <213> Homo sapiens <400> 351 Thr Ile Pro Ile Asp Gly Asn Phe Phe Thr Tyr Thr Arg 1 5 10 <210> 352 <211> 12 <212> PRT <213> Homo sapiens <400> 352 Tyr Cys Ala Gly Trp Ala Asp Lys Ile Gln Gly Arg 1 5 10 <210> 353 <211> 24 <212> PRT <213> Homo sapiens <400> 353 Tyr Ile Leu Gly Asn Pro Leu Thr Pro Gly Val Thr Gln Gly Pro Gln 1 5 10 15 Ile Asp Lys Glu Gln Tyr Asp Lys 20 <210> 354 <211> 11 <212> PRT <213> Homo sapiens <400> 354 Val Ala Phe Thr Gly Ser Thr Glu Val Gly Lys 1 5 10 <210> 355 <211> 9 <212> PRT <213> Homo sapiens <400> 355 Asp Leu Cys Gly Ile Val Ala Ser Lys 1 5 <210> 356 <211> 14 <212> PRT <213> Homo sapiens <400> 356 Glu Leu Cys Gln Gly Leu Gly Gln Pro Gly Ser Val Leu Arg 1 5 10 <210> 357 <211> 15 <212> PRT <213> Homo sapiens <400> 357 Glu Leu Ser Leu Ala Gly Asn Glu Leu Gly Asp Glu Gly Ala Arg 1 5 10 15 <210> 358 <211> 10 <212> PRT <213> Homo sapiens <400> 358 Leu Asp Asp Cys Gly Leu Thr Glu Ala Arg 1 5 10 <210> 359 <211> 22 <212> PRT <213> Homo sapiens <400> 359 Ser Asn Glu Leu Gly Asp Val Gly Val His Cys Val Leu Gln Gly Leu 1 5 10 15 Gln Thr Pro Ser Cys Lys 20 <210> 360 <211> 12 <212> PRT <213> Homo sapiens <400> 360 Thr Leu Trp Ile Trp Glu Cys Gly Ile Thr Ala Lys 1 5 10 <210> 361 <211> 11 <212> PRT <213> Homo sapiens <400> 361 Val Asn Pro Ala Leu Ala Glu Leu Asn Leu Arg 1 5 10 <210> 362 <211> 15 <212> PRT <213> Homo sapiens <400> 362 Trp Ala Glu Leu Leu Pro Leu Leu Gln Gln Cys Gln Val Val Arg 1 5 10 15 <210> 363 <211> 12 <212> PRT <213> Homo sapiens <400> 363 Leu Glu Ser Cys Gly Val Thr Ser Asp Asn Cys Arg 1 5 10 <210> 364 <211> 10 <212> PRT <213> Homo sapiens <400> 364 Glu Leu Asp Leu Asn Ser Val Leu Leu Lys 1 5 10 <210> 365 <211> 13 <212> PRT <213> Homo sapiens <400> 365 Gln Glu Val Trp Leu Ala Asn Gly Ala Ala Glu Ser Arg 1 5 10 <210> 366 <211> 21 <212> PRT <213> Homo sapiens <400> 366 Leu Gly Ile Lys Pro Ser Ile Asn Tyr Tyr Gln Val Ala Asp Phe Lys 1 5 10 15 Asp Ala Leu Ala Arg 20 <210> 367 <211> 16 <212> PRT <213> Homo sapiens <400> 367 His Gly Thr Cys Ala Ala Gln Val Asp Ala Leu Asn Ser Gln Lys Lys 1 5 10 15 <210> 368 <211> 15 <212> PRT <213> Homo sapiens <400> 368 His Gly Thr Cys Ala Ala Gln Val Asp Ala Leu Asn Ser Gln Lys 1 5 10 15 <210> 369 <211> 8 <212> PRT <213> Homo sapiens <400> 369 Leu Ala Leu Leu Glu Glu Ala Arg 1 5 <210> 370 <211> 11 <212> PRT <213> Homo sapiens <400> 370 Ala Leu Asn Ser Ile Ile Asp Val Tyr His Lys 1 5 10 <210> 371 <211> 16 <212> PRT <213> Homo sapiens <400> 371 Ala Leu Asn Ser Ile Ile Asp Val Tyr His Lys Tyr Ser Leu Ile Lys 1 5 10 15 <210> 372 <211> 16 <212> PRT <213> Homo sapiens <400> 372 Asp Asp Leu Lys Lys Leu Leu Glu Thr Glu Cys Pro Gln Tyr Ile Arg 1 5 10 15 <210> 373 <211> 21 <212> PRT <213> Homo sapiens <400> 373 Glu Leu Asp Ile Asn Thr Asp Gly Ala Val Asn Phe Gln Glu Phe Leu 1 5 10 15 Ile Leu Val Ile Lys 20 <210> 374 <211> 7 <212> PRT <213> Homo sapiens <400> 374 Gly Ala Asp Val Trp Phe Lys 1 5 <210> 375 <211> 8 <212> PRT <213> Homo sapiens <400> 375 Gly Asn Phe His Ala Val Tyr Arg 1 5 <210> 376 <211> 12 <212> PRT <213> Homo sapiens <400> 376 Gly Asn Phe His Ala Val Tyr Arg Asp Asp Leu Lys 1 5 10 <210> 377 <211> 13 <212> PRT <213> Homo sapiens <400> 377 Gly Asn Phe His Ala Val Tyr Arg Asp Asp Leu Lys Lys 1 5 10 <210> 378 <211> 12 <212> PRT <213> Homo sapiens <400> 378 Lys Leu Leu Glu Thr Glu Cys Pro Gln Tyr Ile Arg 1 5 10 <210> 379 <211> 11 <212> PRT <213> Homo sapiens <400> 379 Leu Leu Glu Thr Glu Cys Pro Gln Tyr Ile Arg 1 5 10 <210> 380 <211> 8 <212> PRT <213> Homo sapiens <400> 380 Met Gly Val Ala Ala His Lys Lys 1 5 <210> 381 <211> 7 <212> PRT <213> Homo sapiens <400> 381 Met Leu Thr Glu Leu Glu Lys 1 5 <210> 382 <211> 7 <212> PRT <213> Homo sapiens <400> 382 Asp Leu Gln Asn Phe Leu Lys 1 5 <210> 383 <211> 8 <212> PRT <213> Homo sapiens <400> 383 Asp Leu Gln Asn Phe Leu Lys Lys 1 5 <210> 384 <211> 11 <212> PRT <213> Homo sapiens <400> 384 Asp Leu Gln Asn Phe Leu Lys Lys Glu Asn Lys 1 5 10 <210> 385 <211> 12 <212> PRT <213> Homo sapiens <400> 385 Glu Leu Val Arg Lys Asp Leu Gln Asn Phe Leu Lys 1 5 10 <210> 386 <211> 8 <212> PRT <213> Homo sapiens <400> 386 Lys Asp Leu Gln Asn Phe Leu Lys 1 5 <210> 387 <211> 9 <212> PRT <213> Homo sapiens <400> 387 Lys Asp Leu Gln Asn Phe Leu Lys Lys 1 5 <210> 388 <211> 13 <212> PRT <213> Homo sapiens <400> 388 Leu Gly His Pro Asp Thr Leu Asn Gln Gly Glu Phe Lys 1 5 10 <210> 389 <211> 17 <212> PRT <213> Homo sapiens <400> 389 Leu Gly His Pro Asp Thr Leu Asn Gln Gly Glu Phe Lys Glu Leu Val 1 5 10 15 Arg <210> 390 <211> 8 <212> PRT <213> Homo sapiens <400> 390 Leu Thr Trp Ala Ser His Glu Lys 1 5 <210> 391 <211> 21 <212> PRT <213> Homo sapiens <400> 391 Met His Glu Gly Asp Glu Gly Pro Gly His His His Lys Pro Gly Leu 1 5 10 15 Gly Glu Gly Thr Pro 20 <210> 392 <211> 15 <212> PRT <213> Homo sapiens <400> 392 Asn Ile Glu Thr Ile Ile Asn Thr Phe His Gln Tyr Ser Val Lys 1 5 10 15 <210> 393 <211> 28 <212> PRT <213> Homo sapiens <400> 393 Asn Ile Glu Thr Ile Ile Asn Thr Phe His Gln Tyr Ser Val Lys Leu 1 5 10 15 Gly His Pro Asp Thr Leu Asn Gln Gly Glu Phe Lys 20 25 <210> 394 <211> 9 <212> PRT <213> Homo sapiens <400> 394 Thr Cys Lys Met Ser Gln Leu Glu Arg 1 5 <210> 395 <211> 15 <212> PRT <213> Homo sapiens <400> 395 Val Ile Glu His Ile Met Glu Asp Leu Asp Thr Asn Ala Asp Lys 1 5 10 15 <210> 396 <211> 17 <212> PRT <213> Homo sapiens <400> 396 Ala Cys Pro Leu Asp Gln Ala Ile Gly Leu Leu Val Ala Ile Phe His 1 5 10 15 Lys <210> 397 <211> 12 <212> PRT <213> Homo sapiens <400> 397 Glu Leu Ile Gln Lys Glu Leu Thr Ile Gly Ser Lys 1 5 10 <210> 398 <211> 20 <212> PRT <213> Homo sapiens <400> 398 Glu Leu Ile Gln Lys Glu Leu Thr Ile Gly Ser Lys Leu Gln Asp Ala 1 5 10 15 Glu Ile Ala Arg 20 <210> 399 <211> 15 <212> PRT <213> Homo sapiens <400> 399 Glu Leu Lys Glu Leu Ile Gln Lys Glu Leu Thr Ile Gly Ser Lys 1 5 10 15 <210> 400 <211> 15 <212> PRT <213> Homo sapiens <400> 400 Glu Leu Thr Ile Gly Ser Lys Leu Gln Asp Ala Glu Ile Ala Arg 1 5 10 15 <210> 401 <211> 9 <212> PRT <213> Homo sapiens <400> 401 Lys Glu Leu Lys Glu Leu Ile Gln Lys 1 5 <210> 402 <211> 8 <212> PRT <213> Homo sapiens <400> 402 Leu Gln Asp Ala Glu Ile Ala Arg 1 5 <210> 403 <211> 28 <212> PRT <213> Homo sapiens <400> 403 Asn Lys Asp Gln Glu Val Asn Phe Gln Glu Tyr Val Thr Phe Leu Gly 1 5 10 15 Ala Leu Ala Leu Ile Tyr Asn Glu Ala Leu Lys Gly 20 25 <210> 404 <211> 13 <212> PRT <213> Homo sapiens <400> 404 Tyr Ser Gly Arg Glu Gly Asp Lys His Thr Leu Ser Lys 1 5 10 <210> 405 <211> 16 <212> PRT <213> Homo sapiens <400> 405 Phe Pro Glu Pro Gly Ala Ile Lys Val Pro Glu Gln Gly Tyr Thr Lys 1 5 10 15 <210> 406 <211> 17 <212> PRT <213> Homo sapiens <400> 406 Leu Pro Glu Pro Cys Pro Ser Thr Val Thr Pro Gly Pro Ala Gln Gln 1 5 10 15 Lys <210> 407 <211> 16 <212> PRT <213> Homo sapiens <400> 407 Gln Pro Ser Gln Pro Pro Pro Gln Glu Ile Phe Val Pro Thr Thr Lys 1 5 10 15 <210> 408 <211> 22 <212> PRT <213> Homo sapiens <400> 408 Gln Pro Ser Gln Pro Pro Pro Gln Glu Ile Phe Val Pro Thr Thr Lys 1 5 10 15 Glu Pro Cys His Ser Lys 20 <210> 409 <211> 15 <212> PRT <213> Homo sapiens <400> 409 Gln Thr Phe Thr Pro Pro Pro Gln Leu Gln Gln Gln Gln Val Lys 1 5 10 15 <210> 410 <211> 16 <212> PRT <213> Homo sapiens <400> 410 Val Pro Asp Gln Gly Phe Ile Lys Phe Pro Glu Pro Gly Ala Ile Lys 1 5 10 15 <210> 411 <211> 16 <212> PRT <213> Homo sapiens <400> 411 Val Pro Glu Pro Gly Cys Thr Lys Val Pro Glu Pro Gly Cys Thr Lys 1 5 10 15 <210> 412 <211> 16 <212> PRT <213> Homo sapiens <400> 412 Val Pro Gln Pro Gly Asn Thr Lys Ile Pro Glu Pro Gly Cys Thr Lys 1 5 10 15 <210> 413 <211> 12 <212> PRT <213> Homo sapiens <400> 413 Val Ala Gly Gln Asp Gly Ser Val Val Gln Phe Lys 1 5 10 <210> 414 <211> 10 <212> PRT <213> Homo sapiens <400> 414 Glu Glu Asp Ile Asp Glu Asn Leu Leu Phe 1 5 10 <210> 415 <211> 29 <212> PRT <213> Homo sapiens <400> 415 Glu His Ala Asn Ser Lys Gln Glu Glu Asp Asn Thr Gln Ser Asp Asp 1 5 10 15 Ile Leu Glu Glu Ser Asp Gln Pro Thr Gln Val Ser Lys 20 25 <210> 416 <211> 15 <212> PRT <213> Homo sapiens <400> 416 Thr Gly Leu Glu Ala Ile Ser Asn His Lys Glu Thr Glu Glu Lys 1 5 10 15 <210> 417 <211> 13 <212> PRT <213> Homo sapiens <400> 417 Gly His Gln Leu Gln Leu Asp Tyr Phe Gly Ala Cys Lys 1 5 10 <210> 418 <211> 19 <212> PRT <213> Homo sapiens <400> 418 His Ser Ala Ser Asp Asp Tyr Phe Ile Pro Ser Gln Ala Phe Leu Glu 1 5 10 15 Ala Glu Arg <210> 419 <211> 21 <212> PRT <213> Homo sapiens <400> 419 Asn His Gly Val Asp Asp Asp Gly Asp Asp Asp Gly Asp Asp Gly Gly 1 5 10 15 Thr Asp Gly Pro Arg 20 <210> 420 <211> 16 <212> PRT <213> Homo sapiens <400> 420 Ser Ile Pro Thr Cys Thr Asp Phe Glu Val Ile Gln Phe Pro Leu Arg 1 5 10 15 <210> 421 <211> 8 <212> PRT <213> Homo sapiens <400> 421 Ala Asn Phe Glu Asn Leu Ala Lys 1 5 <210> 422 <211> 13 <212> PRT <213> Homo sapiens <400> 422 Tyr Gly Leu Phe Pro Ala Asn Tyr Val Glu Leu Arg Gln 1 5 10 <210> 423 <211> 10 <212> PRT <213> Homo sapiens <400> 423 Tyr Gly Val Gln Ala Asp Arg Val Asp Lys 1 5 10 <210> 424 <211> 14 <212> PRT <213> Homo sapiens <400> 424 Ala Asp Asp Leu Gly Lys Gly Gly Asn Glu Glu Ser Thr Lys 1 5 10 <210> 425 <211> 21 <212> PRT <213> Homo sapiens <400> 425 Ala Asp Asp Leu Gly Lys Gly Gly Asn Glu Glu Ser Thr Lys Thr Gly 1 5 10 15 Asn Ala Gly Ser Arg 20 <210> 426 <211> 23 <212> PRT <213> Homo sapiens <400> 426 Ala Thr Lys Ala Val Cys Val Leu Lys Gly Asp Gly Pro Val Gln Gly 1 5 10 15 Ile Ile Asn Phe Glu Gln Lys 20 <210> 427 <211> 20 <212> PRT <213> Homo sapiens <400> 427 Ala Val Cys Val Leu Lys Gly Asp Gly Pro Val Gln Gly Ile Ile Asn 1 5 10 15 Phe Glu Gln Lys 20 <210> 428 <211> 13 <212> PRT <213> Homo sapiens <400> 428 Glu Ser Asn Gly Pro Val Lys Val Trp Gly Ser Ile Lys 1 5 10 <210> 429 <211> 14 <212> PRT <213> Homo sapiens <400> 429 Gly Asp Gly Pro Val Gln Gly Ile Ile Asn Phe Glu Gln Lys 1 5 10 <210> 430 <211> 36 <212> PRT <213> Homo sapiens <400> 430 His Val Gly Asp Leu Gly Asn Val Thr Ala Asp Lys Asp Gly Val Ala 1 5 10 15 Asp Val Ser Ile Glu Asp Ser Val Ile Ser Leu Ser Gly Asp His Cys 20 25 30 Ile Ile Gly Arg 35 <210> 431 <211> 14 <212> PRT <213> Homo sapiens <400> 431 Ala Ile Trp Asn Val Ile Asn Trp Glu Asn Val Thr Glu Arg 1 5 10 <210> 432 <211> 14 <212> PRT <213> Homo sapiens <400> 432 Gly Asp Val Thr Ala Gln Ile Ala Leu Gln Pro Ala Leu Lys 1 5 10 <210> 433 <211> 19 <212> PRT <213> Homo sapiens <400> 433 Asp Ala Gly Gly Lys Ser Trp Cys Pro Asp Cys Val Gln Ala Glu Pro 1 5 10 15 Val Val Arg <210> 434 <211> 14 <212> PRT <213> Homo sapiens <400> 434 Ser Trp Cys Pro Asp Cys Val Gln Ala Glu Pro Val Val Arg 1 5 10 <210> 435 <211> 10 <212> PRT <213> Homo sapiens <400> 435 Thr Ile Phe Ala Tyr Phe Thr Gly Ser Lys 1 5 10 <210> 436 <211> 13 <212> PRT <213> Homo sapiens <400> 436 Ala Ala Asp Asp Thr Trp Glu Pro Phe Ala Ser Gly Lys 1 5 10 <210> 437 <211> 13 <212> PRT <213> Homo sapiens <400> 437 Gly Ser Pro Ala Ile Asn Val Ala Val His Val Phe Arg 1 5 10 <210> 438 <211> 14 <212> PRT <213> Homo sapiens <400> 438 Lys Ala Ala Asp Asp Thr Trp Glu Pro Phe Ala Ser Gly Lys 1 5 10 <210> 439 <211> 24 <212> PRT <213> Homo sapiens <400> 439 Arg Tyr Thr Ile Ala Ala Leu Leu Ser Pro Tyr Ser Tyr Ser Thr Thr 1 5 10 15 Ala Val Val Thr Asn Pro Lys Glu 20 <210> 440 <211> 22 <212> PRT <213> Homo sapiens <400> 440 Thr Ser Glu Ser Gly Glu Leu His Gly Leu Thr Thr Glu Glu Glu Phe 1 5 10 15 Val Glu Gly Ile Tyr Lys 20 <210> 441 <211> 19 <212> PRT <213> Homo sapiens <400> 441 Val Leu Asp Ala Val Arg Gly Ser Pro Ala Ile Asn Val Ala Val His 1 5 10 15 Val Phe Arg <210> 442 <211> 23 <212> PRT <213> Homo sapiens <400> 442 Tyr Thr Ile Ala Ala Leu Leu Ser Pro Tyr Ser Tyr Ser Thr Thr Ala 1 5 10 15 Val Val Thr Asn Pro Lys Glu 20 <210> 443 <211> 11 <212> PRT <213> Homo sapiens <400> 443 Ala Gly Ile Thr Thr Ile Glu Ala Val Lys Arg 1 5 10 <210> 444 <211> 15 <212> PRT <213> Homo sapiens <400> 444 His Ile Ala Glu Glu Ala Asp Arg Lys Tyr Glu Glu Val Ala Arg 1 5 10 15 <210> 445 <211> 10 <212> PRT <213> Homo sapiens <400> 445 Ile Gln Leu Val Glu Glu Glu Leu Asp Arg 1 5 10 <210> 446 <211> 14 <212> PRT <213> Homo sapiens <400> 446 Ile Gln Leu Val Glu Glu Glu Leu Asp Arg Ala Gln Glu Arg 1 5 10 <210> 447 <211> 14 <212> PRT <213> Homo sapiens <400> 447 Ile Gln Val Leu Gln Gln Gln Ala Asp Asp Ala Glu Glu Arg 1 5 10 <210> 448 <211> 17 <212> PRT <213> Homo sapiens <400> 448 Ile Gln Val Leu Gln Gln Gln Ala Asp Asp Ala Glu Glu Arg Ala Glu 1 5 10 15 Arg <210> 449 <211> 15 <212> PRT <213> Homo sapiens <400> 449 Lys Ile Gln Val Leu Gln Gln Gln Ala Asp Asp Ala Glu Glu Arg 1 5 10 15 <210> 450 <211> 15 <212> PRT <213> Homo sapiens <400> 450 Arg Ile Gln Leu Val Glu Glu Glu Leu Asp Arg Ala Gln Glu Arg 1 5 10 15 <210> 451 <211> 10 <212> PRT <213> Homo sapiens <400> 451 Thr Ile Asp Asp Leu Glu Asp Lys Leu Lys 1 5 10 <210> 452 <211> 16 <212> PRT <213> Homo sapiens <400> 452 Thr Ile Thr Leu Glu Val Glu Pro Ser Asp Thr Ile Glu Asn Val Lys 1 5 10 15 <210> 453 <211> 16 <212> PRT <213> Homo sapiens <400> 453 Asp Glu Arg Lys Asn Pro Asp Ser Gln Tyr Gly Glu Leu Ile Glu Lys 1 5 10 15 <210> 454 <211> 17 <212> PRT <213> Homo sapiens <400> 454 Ile Val Glu Lys Tyr Gly Tyr Thr His Leu Ser Ala Gly Glu Leu Leu 1 5 10 15 Arg <210> 455 <211> 13 <212> PRT <213> Homo sapiens <400> 455 Lys Asn Pro Asp Ser Gln Tyr Gly Glu Leu Ile Glu Lys 1 5 10 <210> 456 <211> 10 <212> PRT <213> Homo sapiens <400> 456 Asn Lys Phe Leu Ile Asp Gly Phe Pro Arg 1 5 10 <210> 457 <211> 10 <212> PRT <213> Homo sapiens <400> 457 Asn Gln Asp Asn Leu Gln Gly Trp Asn Lys 1 5 10 <210> 458 <211> 11 <212> PRT <213> Homo sapiens <400> 458 Ser Asp Asp Asn Arg Glu Ser Leu Glu Lys Arg 1 5 10 <210> 459 <211> 13 <212> PRT <213> Homo sapiens <400> 459 Tyr Gly Tyr Thr His Leu Ser Ala Gly Glu Leu Leu Arg 1 5 10 <210> 460 <211> 7 <212> PRT <213> Homo sapiens <400> 460 Ala Cys Gln Gln Phe Leu Lys 1 5 <210> 461 <211> 9 <212> PRT <213> Homo sapiens <400> 461 Lys Gln Cys Pro Cys Asp His Phe Lys 1 5 <210> 462 <211> 17 <212> PRT <213> Homo sapiens <400> 462 Trp Leu Gln Glu Gly Gly Gln Glu Cys Glu Cys Lys Asp Trp Phe Leu 1 5 10 15 Arg <210> 463 <211> 22 <212> PRT <213> Homo sapiens <400> 463 Glu Val Val Ser Leu Thr Glu Ala Cys Cys Ala Glu Gly Ala Asp Pro 1 5 10 15 Asp Cys Tyr Asp Thr Arg 20 <210> 464 <211> 8 <212> PRT <213> Homo sapiens <400> 464 Phe Glu Asp Cys Cys Gln Glu Lys 1 5 <210> 465 <211> 22 <212> PRT <213> Homo sapiens <400> 465 His Gln Pro Gln Glu Phe Pro Thr Tyr Val Glu Pro Thr Asn Asp Glu 1 5 10 15 Ile Cys Glu Ala Phe Arg 20 <210> 466 <211> 26 <212> PRT <213> Homo sapiens <400> 466 His Gln Pro Gln Glu Phe Pro Thr Tyr Val Glu Pro Thr Asn Asp Glu 1 5 10 15 Ile Cys Glu Ala Phe Arg Lys Asp Pro Lys 20 25 <210> 467 <211> 15 <212> PRT <213> Homo sapiens <400> 467 Lys Phe Pro Ser Gly Thr Phe Glu Gln Val Ser Gln Leu Val Lys 1 5 10 15 <210> 468 <211> 11 <212> PRT <213> Homo sapiens <400> 468 Leu Lys Ala Lys Leu Pro Asp Ala Thr Pro Lys 1 5 10 <210> 469 <211> 11 <212> PRT <213> Homo sapiens <400> 469 Asn Ser Lys Phe Glu Asp Cys Cys Gln Glu Lys 1 5 10 <210> 470 <211> 11 <212> PRT <213> Homo sapiens <400> 470 Arg Thr His Leu Pro Glu Val Phe Leu Ser Lys 1 5 10 <210> 471 <211> 20 <212> PRT <213> Homo sapiens <400> 471 Ser Cys Glu Ser Asn Ser Pro Phe Pro Val His Pro Gly Thr Ala Glu 1 5 10 15 Cys Cys Thr Lys 20 <210> 472 <211> 18 <212> PRT <213> Homo sapiens <400> 472 Ser Leu Gly Glu Cys Cys Asp Val Glu Asp Ser Thr Thr Cys Phe Asn 1 5 10 15 Ala Lys <210> 473 <211> 24 <212> PRT <213> Homo sapiens <400> 473 Ser Leu Gly Glu Cys Cys Asp Val Glu Asp Ser Thr Thr Cys Phe Asn 1 5 10 15 Ala Lys Gly Pro Leu Leu Lys Lys 20 <210> 474 <211> 10 <212> PRT <213> Homo sapiens <400> 474 Thr His Leu Pro Glu Val Phe Leu Ser Lys 1 5 10 <210> 475 <211> 14 <212> PRT <213> Homo sapiens <400> 475 Val Cys Ser Gln Tyr Ala Ala Tyr Gly Glu Lys Lys Ser Arg 1 5 10 <210> 476 <211> 11 <212> PRT <213> Homo sapiens <400> 476 Val Met Asp Lys Tyr Thr Phe Glu Leu Ser Arg 1 5 10 <210> 477 <211> 27 <212> PRT <213> Homo sapiens <400> 477 Cys Gln Cys Asp Glu Leu Cys Ser Tyr Tyr Gln Ser Cys Cys Thr Asp 1 5 10 15 Tyr Thr Ala Glu Cys Lys Pro Gln Val Thr Arg 20 25 <210> 478 <211> 15 <212> PRT <213> Homo sapiens <400> 478 Asp Val Trp Gly Ile Glu Gly Pro Ile Asp Ala Ala Phe Thr Arg 1 5 10 15 <210> 479 <211> 10 <212> PRT <213> Homo sapiens <400> 479 Gly Gln Tyr Cys Tyr Glu Leu Asp Glu Lys 1 5 10 <210> 480 <211> 15 <212> PRT <213> Homo sapiens <400> 480 Ser Ile Ala Gln Tyr Trp Leu Gly Cys Pro Ala Pro Gly His Leu 1 5 10 15 <210> 481 <211> 9 <212> PRT <213> Homo sapiens <400> 481 Ala Leu Phe Val Ser Glu Glu Glu Lys 1 5 <210> 482 <211> 10 <212> PRT <213> Homo sapiens <400> 482 Ala Leu Phe Val Ser Glu Glu Glu Lys Lys 1 5 10 <210> 483 <211> 8 <212> PRT <213> Homo sapiens <400> 483 Cys Leu Val Asn Leu Ile Glu Lys 1 5 <210> 484 <211> 10 <212> PRT <213> Homo sapiens <400> 484 Asp Ala Gln Tyr Ala Pro Gly Tyr Asp Lys 1 5 10 <210> 485 <211> 12 <212> PRT <213> Homo sapiens <400> 485 Asp Ala Gln Tyr Ala Pro Gly Tyr Asp Lys Val Lys 1 5 10 <210> 486 <211> 21 <212> PRT <213> Homo sapiens <400> 486 Asp Ala Gln Tyr Ala Pro Gly Tyr Asp Lys Val Lys Asp Ile Ser Glu 1 5 10 15 Val Val Thr Pro Arg 20 <210> 487 <211> 9 <212> PRT <213> Homo sapiens <400> 487 Asp Ile Ser Glu Val Val Thr Pro Arg 1 5 <210> 488 <211> 16 <212> PRT <213> Homo sapiens <400> 488 Glu Ala Gly Ile Pro Glu Phe Tyr Asp Tyr Asp Val Ala Leu Ile Lys 1 5 10 15 <210> 489 <211> 10 <212> PRT <213> Homo sapiens <400> 489 Glu Glu Leu Leu Pro Ala Gln Asp Ile Lys 1 5 10 <210> 490 <211> 11 <212> PRT <213> Homo sapiens <400> 490 Glu Lys Leu Gln Asp Glu Asp Leu Gly Phe Leu 1 5 10 <210> 491 <211> 17 <212> PRT <213> Homo sapiens <400> 491 Phe Leu Cys Thr Gly Gly Val Ser Pro Tyr Ala Asp Pro Asn Thr Cys 1 5 10 15 Arg <210> 492 <211> 28 <212> PRT <213> Homo sapiens <400> 492 Phe Leu Cys Thr Gly Gly Val Ser Pro Tyr Ala Asp Pro Asn Thr Cys 1 5 10 15 Arg Gly Asp Ser Gly Gly Pro Leu Ile Val His Lys 20 25 <210> 493 <211> 29 <212> PRT <213> Homo sapiens <400> 493 Phe Leu Cys Thr Gly Gly Val Ser Pro Tyr Ala Asp Pro Asn Thr Cys 1 5 10 15 Arg Gly Asp Ser Gly Gly Pro Leu Ile Val His Lys Arg 20 25 <210> 494 <211> 9 <212> PRT <213> Homo sapiens <400> 494 Lys Asp Asn Glu Gln His Val Phe Lys 1 5 <210> 495 <211> 11 <212> PRT <213> Homo sapiens <400> 495 Leu Glu Asp Ser Val Thr Tyr His Cys Ser Arg 1 5 10 <210> 496 <211> 24 <212> PRT <213> Homo sapiens <400> 496 Leu Leu Gln Glu Gly Gln Ala Leu Glu Tyr Val Cys Pro Ser Gly Phe 1 5 10 15 Tyr Pro Tyr Pro Val Gln Thr Arg 20 <210> 497 <211> 11 <212> PRT <213> Homo sapiens <400> 497 Leu Pro Pro Thr Thr Thr Cys Gln Gln Gln Lys 1 5 10 <210> 498 <211> 21 <212> PRT <213> Homo sapiens <400> 498 Leu Pro Pro Thr Thr Thr Cys Gln Gln Gln Lys Glu Glu Leu Leu Pro 1 5 10 15 Ala Gln Asp Ile Lys 20 <210> 499 <211> 9 <212> PRT <213> Homo sapiens <400> 499 Leu Gln Asp Glu Asp Leu Gly Phe Leu 1 5 <210> 500 <211> 9 <212> PRT <213> Homo sapiens <400> 500 Ser Thr Gly Ser Trp Ser Thr Leu Lys 1 5 <210> 501 <211> 17 <212> PRT <213> Homo sapiens <400> 501 Ser Thr Gly Ser Trp Ser Thr Leu Lys Thr Gln Asp Gln Lys Thr Val 1 5 10 15 Arg <210> 502 <211> 9 <212> PRT <213> Homo sapiens <400> 502 Val Ala Ser Tyr Gly Val Lys Pro Arg 1 5 <210> 503 <211> 14 <212> PRT <213> Homo sapiens <400> 503 Val Ser Glu Ala Asp Ser Ser Asn Ala Asp Trp Val Thr Lys 1 5 10 <210> 504 <211> 25 <212> PRT <213> Homo sapiens <400> 504 Trp Ser Gly Gln Thr Ala Ile Cys Asp Asn Gly Ala Gly Tyr Cys Ser 1 5 10 15 Asn Pro Gly Ile Pro Ile Gly Thr Arg 20 25 <210> 505 <211> 26 <212> PRT <213> Homo sapiens <400> 505 Trp Ser Gly Gln Thr Ala Ile Cys Asp Asn Gly Ala Gly Tyr Cys Ser 1 5 10 15 Asn Pro Gly Ile Pro Ile Gly Thr Arg Lys 20 25 <210> 506 <211> 11 <212> PRT <213> Homo sapiens <400> 506 Tyr Gly Leu Val Thr Tyr Ala Thr Tyr Pro Lys 1 5 10 <210> 507 <211> 15 <212> PRT <213> Homo sapiens <400> 507 Tyr Gly Leu Val Thr Tyr Ala Thr Tyr Pro Lys Ile Trp Val Lys 1 5 10 15 <210> 508 <211> 18 <212> PRT <213> Homo sapiens <400> 508 Tyr Gly Gln Thr Ile Arg Pro Ile Cys Leu Pro Cys Thr Glu Gly Thr 1 5 10 15 Thr Arg <210> 509 <211> 15 <212> PRT <213> Homo sapiens <400> 509 Glu Tyr Ala Gln Asn Ile Trp Asn Val Glu Pro Ser Asp Leu Lys 1 5 10 15 <210> 510 <211> 10 <212> PRT <213> Homo sapiens <400> 510 Phe Ser Gln Phe Leu Glu Thr Glu Tyr Lys 1 5 10 <210> 511 <211> 12 <212> PRT <213> Homo sapiens <400> 511 Ile Phe Val Asp Ile Glu Lys Leu Pro Trp Ser Lys 1 5 10 <210> 512 <211> 14 <212> PRT <213> Homo sapiens <400> 512 Ile Gly Glu Asp Tyr Val Lys Asp Leu Ser Gln Leu Thr Lys 1 5 10 <210> 513 <211> 17 <212> PRT <213> Homo sapiens <400> 513 Leu Lys Gln Glu Tyr Phe Val Val Ala Ala Thr Leu Gln Asp Ile Ile 1 5 10 15 Arg <210> 514 <211> 14 <212> PRT <213> Homo sapiens <400> 514 Leu Val Ile Asp Gln Ile Asp Asn Gly Phe Phe Ser Pro Lys 1 5 10 <210> 515 <211> 14 <212> PRT <213> Homo sapiens <400> 515 Val Pro Thr Ala Asn Val Ser Val Val Asp Leu Thr Cys Arg 1 5 10 <210> 516 <211> 24 <212> PRT <213> Homo sapiens <400> 516 Val Ile His Asp Asn Phe Gly Ile Val Glu Gly Leu Met Thr Thr Val 1 5 10 15 His Ala Ile Thr Ala Thr Gln Lys 20 <210> 517 <211> 8 <212> PRT <213> Homo sapiens <400> 517 Val Gly Val Asn Gly Phe Gly Arg 1 5 <210> 518 <211> 18 <212> PRT <213> Homo sapiens <400> 518 Leu Val Ile Asn Gly Asn Pro Ile Thr Ile Phe Gln Glu Arg Asp Pro 1 5 10 15 Ser Lys <210> 519 <211> 14 <212> PRT <213> Homo sapiens <400> 519 Leu Val Ile Asn Gly Asn Pro Ile Thr Ile Phe Gln Glu Arg 1 5 10 <210> 520 <211> 14 <212> PRT <213> Homo sapiens <400> 520 Leu Ile Ser Trp Tyr Asp Asn Glu Phe Gly Tyr Ser Asn Arg 1 5 10 <210> 521 <211> 17 <212> PRT <213> Homo sapiens <400> 521 Ile Ile Ser Asn Ala Ser Cys Thr Thr Asn Cys Leu Ala Pro Leu Ala 1 5 10 15 Lys <210> 522 <211> 12 <212> PRT <213> Homo sapiens <400> 522 Gly Lys Val Lys Val Gly Val Asn Gly Phe Gly Arg 1 5 10 <210> 523 <211> 15 <212> PRT <213> Homo sapiens <400> 523 Gly Ala Leu Gln Asn Ile Ile Pro Ala Ser Thr Gly Ala Ala Lys 1 5 10 15 <210> 524 <211> 18 <212> PRT <213> Homo sapiens <400> 524 Asp Gly Arg Gly Ala Leu Gln Asn Ile Ile Pro Ala Ser Thr Gly Ala 1 5 10 15 Ala Lys <210> 525 <211> 23 <212> PRT <213> Homo sapiens <400> 525 Ala Glu Asn Gly Lys Leu Val Ile Asn Gly Asn Pro Ile Thr Ile Phe 1 5 10 15 Gln Glu Arg Asp Pro Ser Lys 20 <210> 526 <211> 19 <212> PRT <213> Homo sapiens <400> 526 Ala Glu Asn Gly Lys Leu Val Ile Asn Gly Asn Pro Ile Thr Ile Phe 1 5 10 15 Gln Glu Arg <210> 527 <211> 9 <212> PRT <213> Homo sapiens <400> 527 Ala Ile Glu Asn Glu Leu Leu Ala Arg 1 5 <210> 528 <211> 11 <212> PRT <213> Homo sapiens <400> 528 Ala Thr Asn Trp Gly Ser Leu Leu Gln Asp Lys 1 5 10 <210> 529 <211> 18 <212> PRT <213> Homo sapiens <400> 529 Tyr Ile Ser Leu Ile Tyr Thr Asn Tyr Glu Ala Gly Lys Asp Asp Tyr 1 5 10 15 Val Lys <210> 530 <211> 13 <212> PRT <213> Homo sapiens <400> 530 Tyr Ile Ser Leu Ile Tyr Thr Asn Tyr Glu Ala Gly Lys 1 5 10 <210> 531 <211> 13 <212> PRT <213> Homo sapiens <400> 531 Pro Pro Tyr Thr Val Val Tyr Phe Pro Val Arg Gly Arg 1 5 10 <210> 532 <211> 11 <212> PRT <213> Homo sapiens <400> 532 Pro Pro Tyr Thr Val Val Tyr Phe Pro Val Arg 1 5 10 <210> 533 <211> 11 <212> PRT <213> Homo sapiens <400> 533 Met Leu Leu Ala Asp Gln Gly Gln Ser Trp Lys 1 5 10 <210> 534 <211> 21 <212> PRT <213> Homo sapiens <400> 534 Leu Lys Ala Phe Leu Ala Ser Pro Glu Tyr Val Asn Leu Pro Ile Asn 1 5 10 15 Gly Asn Gly Lys Gln 20 <210> 535 <211> 20 <212> PRT <213> Homo sapiens <400> 535 Leu Lys Ala Phe Leu Ala Ser Pro Glu Tyr Val Asn Leu Pro Ile Asn 1 5 10 15 Gly Asn Gly Lys 20 <210> 536 <211> 20 <212> PRT <213> Homo sapiens <400> 536 Phe Gln Asp Gly Asp Leu Thr Leu Tyr Gln Ser Asn Thr Ile Leu Arg 1 5 10 15 His Leu Gly Arg 20 <210> 537 <211> 16 <212> PRT <213> Homo sapiens <400> 537 Phe Gln Asp Gly Asp Leu Thr Leu Tyr Gln Ser Asn Thr Ile Leu Arg 1 5 10 15 <210> 538 <211> 15 <212> PRT <213> Homo sapiens <400> 538 Glu Glu Val Val Thr Val Glu Thr Trp Gln Glu Gly Ser Leu Lys 1 5 10 15 <210> 539 <211> 20 <212> PRT <213> Homo sapiens <400> 539 Cys Lys Tyr Ile Ser Leu Ile Tyr Thr Asn Tyr Glu Ala Gly Lys Asp 1 5 10 15 Asp Tyr Val Lys 20 <210> 540 <211> 10 <212> PRT <213> Homo sapiens <400> 540 Ala Ser Cys Leu Tyr Gly Gln Leu Pro Lys 1 5 10 <210> 541 <211> 20 <212> PRT <213> Homo sapiens <400> 541 Ala Leu Pro Gly Gln Leu Lys Pro Phe Glu Thr Leu Leu Ser Gln Asn 1 5 10 15 Gln Gly Gly Lys 20 <210> 542 <211> 19 <212> PRT <213> Homo sapiens <400> 542 Ala Phe Leu Ala Ser Pro Glu Tyr Val Asn Leu Pro Ile Asn Gly Asn 1 5 10 15 Gly Lys Gln <210> 543 <211> 18 <212> PRT <213> Homo sapiens <400> 543 Ala Phe Leu Ala Ser Pro Glu Tyr Val Asn Leu Pro Ile Asn Gly Asn 1 5 10 15 Gly Lys <210> 544 <211> 14 <212> PRT <213> Homo sapiens <400> 544 Ser Asn Glu Glu Gly Ser Glu Glu Lys Gly Pro Glu Val Arg 1 5 10 <210> 545 <211> 15 <212> PRT <213> Homo sapiens <400> 545 Asn Leu Leu Ser Val Ala Tyr Lys Asn Val Val Gly Gly Gln Arg 1 5 10 15 <210> 546 <211> 8 <212> PRT <213> Homo sapiens <400> 546 Asn Leu Leu Ser Val Ala Tyr Lys 1 5 <210> 547 <211> 7 <212> PRT <213> Homo sapiens <400> 547 Leu Ala Glu Gln Ala Glu Arg 1 5 <210> 548 <211> 9 <212> PRT <213> Homo sapiens <400> 548 Gly Glu Glu Leu Ser Cys Glu Glu Arg 1 5 <210> 549 <211> 14 <212> PRT <213> Homo sapiens <400> 549 Gly Ala Val Glu Lys Gly Glu Glu Leu Ser Cys Glu Glu Arg 1 5 10 <210> 550 <211> 10 <212> PRT <213> Homo sapiens <400> 550 Asp Ser Thr Leu Ile Met Gln Leu Leu Arg 1 5 10 <210> 551 <211> 24 <212> PRT <213> Homo sapiens <400> 551 Asp Asn Leu Thr Leu Trp Thr Ala Asp Asn Ala Gly Glu Glu Gly Gly 1 5 10 15 Glu Ala Pro Gln Glu Pro Gln Ser 20 <210> 552 <211> 13 <212> PRT <213> Homo sapiens <400> 552 Tyr Leu Ala Glu Val Ala Thr Gly Asp Asp Lys Lys Arg 1 5 10 <210> 553 <211> 16 <212> PRT <213> Homo sapiens <400> 553 Ala Ala Gly Val Asn Val Glu Pro Phe Trp Pro Gly Leu Phe Ala Lys 1 5 10 15 <210> 554 <211> 17 <212> PRT <213> Homo sapiens <400> 554 Val Cys Leu Ile Gly Cys Gly Phe Ser Thr Gly Tyr Gly Ser Ala Val 1 5 10 15 Lys <210> 555 <211> 9 <212> PRT <213> Homo sapiens <400> 555 Asn Pro Glu Ser Asn Tyr Cys Leu Lys 1 5 <210> 556 <211> 14 <212> PRT <213> Homo sapiens <400> 556 Lys Pro Phe Ser Ile Glu Glu Val Glu Val Ala Pro Pro Lys 1 5 10 <210> 557 <211> 9 <212> PRT <213> Homo sapiens <400> 557 Ile Asn Glu Gly Phe Asp Leu Leu Arg 1 5 <210> 558 <211> 12 <212> PRT <213> Homo sapiens <400> 558 Ile Cys Lys Asn Pro Glu Ser Asn Tyr Cys Leu Lys 1 5 10 <210> 559 <211> 14 <212> PRT <213> Homo sapiens <400> 559 Glu Leu Gly Ala Thr Glu Cys Ile Asn Pro Gln Asp Tyr Lys 1 5 10 <210> 560 <211> 8 <212> PRT <213> Homo sapiens <400> 560 Ala Ala Val Leu Trp Glu Leu Lys 1 5 <210> 561 <211> 15 <212> PRT <213> Homo sapiens <400> 561 Glu Cys Asn Ala Cys Arg Asn Pro Asp Gly Asn Leu Cys Ile Arg 1 5 10 15 <210> 562 <211> 28 <212> PRT <213> Homo sapiens <400> 562 Phe Pro Val Ile Val Gly His Glu Ala Thr Gly Ile Val Glu Ser Ile 1 5 10 15 Gly Glu Gly Val Thr Thr Val Lys Pro Gly Asp Lys 20 25 <210> 563 <211> 10 <212> PRT <213> Homo sapiens <400> 563 Ile Lys Ile Leu Ala Thr Gly Ile Cys Arg 1 5 10 <210> 564 <211> 8 <212> PRT <213> Homo sapiens <400> 564 Ile Leu Ala Thr Gly Ile Cys Arg 1 5 <210> 565 <211> 15 <212> PRT <213> Homo sapiens <400> 565 Ile Ser Glu Gly Phe Glu Leu Leu Asn Ser Gly Gln Ser Ile Arg 1 5 10 15 <210> 566 <211> 15 <212> PRT <213> Homo sapiens <400> 566 Lys Phe Asp Leu Asp Gln Leu Ile Thr His Val Leu Pro Phe Lys 1 5 10 15 <210> 567 <211> 9 <212> PRT <213> Homo sapiens <400> 567 Asn Pro Asp Gly Asn Leu Cys Ile Arg 1 5 <210> 568 <211> 17 <212> PRT <213> Homo sapiens <400> 568 Val Cys Leu Ile Gly Cys Gly Phe Ser Thr Gly Tyr Gly Ala Ala Val 1 5 10 15 Lys <210> 569 <211> 10 <212> PRT <213> Homo sapiens <400> 569 Val Ile Pro Leu Phe Leu Pro Gln Cys Arg 1 5 10 <210> 570 <211> 26 <212> PRT <213> Homo sapiens <400> 570 Ile Asp Asp Ala Ala Pro Pro Glu Lys Val Cys Leu Ile Gly Cys Gly 1 5 10 15 Phe Ser Thr Gly Tyr Gly Ala Ala Val Lys 20 25 <210> 571 <211> 17 <212> PRT <213> Homo sapiens <400> 571 Tyr Lys Pro Val Cys Asn Gln Val Glu Cys His Pro Tyr Phe Asn Gln 1 5 10 15 Arg <210> 572 <211> 19 <212> PRT <213> Homo sapiens <400> 572 His Ile Asp Ser Ala His Leu Tyr Asn Asn Glu Glu Gln Val Gly Leu 1 5 10 15 Ala Ile Arg <210> 573 <211> 8 <212> PRT <213> Homo sapiens <400> 573 Leu Ala Ile Glu Ala Gly Phe Arg 1 5 <210> 574 <211> 22 <212> PRT <213> Homo sapiens <400> 574 Leu Asn Asp Gly His Phe Met Pro Val Leu Gly Phe Gly Thr Tyr Ala 1 5 10 15 Pro Ala Glu Val Pro Lys 20 <210> 575 <211> 9 <212> PRT <213> Homo sapiens <400> 575 Arg Glu Asp Ile Phe Tyr Thr Ser Lys 1 5 <210> 576 <211> 16 <212> PRT <213> Homo sapiens <400> 576 Ser Lys Asp Ile Val Leu Val Ala Tyr Ser Ala Leu Gly Ser His Arg 1 5 10 15 <210> 577 <211> 8 <212> PRT <213> Homo sapiens <400> 577 Thr Pro Ala Leu Ile Ala Leu Arg 1 5 <210> 578 <211> 11 <212> PRT <213> Homo sapiens <400> 578 Ile Thr Leu Leu Ser Ala Leu Val Glu Thr Arg 1 5 10 <210> 579 <211> 10 <212> PRT <213> Homo sapiens <400> 579 Asn Leu Ala Val Ser Gln Val Val His Lys 1 5 10 <210> 580 <211> 18 <212> PRT <213> Homo sapiens <400> 580 Leu Tyr Gly Ser Glu Ala Phe Ala Thr Asp Phe Gln Asp Ser Ala Ala 1 5 10 15 Ala Lys <210> 581 <211> 9 <212> PRT <213> Homo sapiens <400> 581 Glu Ile Gly Glu Leu Tyr Leu Pro Lys 1 5 <210> 582 <211> 12 <212> PRT <213> Homo sapiens <400> 582 Asp Glu Glu Leu Ser Cys Thr Val Val Glu Leu Lys 1 5 10 <210> 583 <211> 10 <212> PRT <213> Homo sapiens <400> 583 Ala Asp Leu Ser Gly Ile Thr Gly Ala Arg 1 5 10 <210> 584 <211> 11 <212> PRT <213> Homo sapiens <400> 584 Ile Thr Leu Leu Ser Ala Leu Val Glu Thr Arg 1 5 10 <210> 585 <211> 12 <212> PRT <213> Homo sapiens <400> 585 Ala Val His Lys Ala Val Leu Thr Ile Asp Glu Lys 1 5 10 <210> 586 <211> 16 <212> PRT <213> Homo sapiens <400> 586 Asp Thr Glu Glu Glu Asp Phe His Val Asp Gln Val Thr Thr Val Lys 1 5 10 15 <210> 587 <211> 15 <212> PRT <213> Homo sapiens <400> 587 Phe Asn Lys Pro Phe Val Phe Leu Met Ile Glu Gln Asn Thr Lys 1 5 10 15 <210> 588 <211> 8 <212> PRT <213> Homo sapiens <400> 588 Phe Leu Glu Asn Glu Asp Arg Arg 1 5 <210> 589 <211> 14 <212> PRT <213> Homo sapiens <400> 589 Ile Thr Pro Asn Leu Ala Glu Phe Ala Phe Ser Leu Tyr Arg 1 5 10 <210> 590 <211> 14 <212> PRT <213> Homo sapiens <400> 590 Lys Gln Ile Asn Asp Tyr Val Glu Lys Gly Thr Gln Gly Lys 1 5 10 <210> 591 <211> 10 <212> PRT <213> Homo sapiens <400> 591 Leu Ser Ile Thr Gly Thr Tyr Asp Leu Lys 1 5 10 <210> 592 <211> 15 <212> PRT <213> Homo sapiens <400> 592 Leu Gln His Leu Glu Asn Glu Leu Thr His Asp Ile Ile Thr Lys 1 5 10 15 <210> 593 <211> 9 <212> PRT <213> Homo sapiens <400> 593 Leu Ser Ser Trp Val Leu Leu Met Lys 1 5 <210> 594 <211> 19 <212> PRT <213> Homo sapiens <400> 594 Leu Tyr His Ser Glu Ala Phe Thr Val Asn Phe Gly Asp Thr Glu Glu 1 5 10 15 Ala Lys Lys <210> 595 <211> 8 <212> PRT <213> Homo sapiens <400> 595 Gln Ile Asn Asp Tyr Val Glu Lys 1 5 <210> 596 <211> 13 <212> PRT <213> Homo sapiens <400> 596 Gln Ile Asn Asp Tyr Val Glu Lys Gly Thr Gln Gly Lys 1 5 10 <210> 597 <211> 8 <212> PRT <213> Homo sapiens <400> 597 Ser Ala Ser Leu His Leu Pro Lys 1 5 <210> 598 <211> 24 <212> PRT <213> Homo sapiens <400> 598 Thr Leu Asn Gln Pro Asp Ser Gln Leu Gln Leu Thr Thr Gly Asn Gly 1 5 10 15 Leu Phe Leu Ser Glu Gly Leu Lys 20 <210> 599 <211> 10 <212> PRT <213> Homo sapiens <400> 599 Ser Val Leu Gly Gln Leu Gly Ile Thr Lys 1 5 10 <210> 600 <211> 18 <212> PRT <213> Homo sapiens <400> 600 Val Phe Ser Asn Gly Ala Asp Leu Ser Gly Val Thr Glu Glu Ala Pro 1 5 10 15 Leu Lys <210> 601 <211> 18 <212> PRT <213> Homo sapiens <400> 601 Val Phe Ser Asn Gly Ala Asp Leu Ser Gly Val Thr Glu Glu Ala Pro 1 5 10 15 Leu Lys <210> 602 <211> 17 <212> PRT <213> Homo sapiens <400> 602 Val Thr Leu Thr Cys Val Ala Pro Leu Ser Gly Val Asp Phe Gln Leu 1 5 10 15 Arg <210> 603 <211> 20 <212> PRT <213> Homo sapiens <400> 603 Ser Gly Leu Ser Thr Gly Trp Thr Gln Leu Ser Lys Leu Leu Glu Leu 1 5 10 15 Thr Gly Pro Lys 20 <210> 604 <211> 12 <212> PRT <213> Homo sapiens <400> 604 Ser Gly Leu Ser Thr Gly Trp Thr Gln Leu Ser Lys 1 5 10 <210> 605 <211> 10 <212> PRT <213> Homo sapiens <400> 605 Arg Gly Glu Lys Glu Leu Leu Val Pro Arg 1 5 10 <210> 606 <211> 14 <212> PRT <213> Homo sapiens <400> 606 Cys Glu Gly Pro Ile Pro Asp Val Thr Phe Glu Leu Leu Arg 1 5 10 <210> 607 <211> 11 <212> PRT <213> Homo sapiens <400> 607 Ala Thr Trp Ser Gly Ala Val Leu Ala Gly Arg 1 5 10 <210> 608 <211> 22 <212> PRT <213> Homo sapiens <400> 608 Thr Pro Gly Ala Ala Ala Asn Leu Glu Leu Ile Phe Val Gly Pro Gln 1 5 10 15 His Ala Gly Asn Tyr Arg 20 <210> 609 <211> 9 <212> PRT <213> Homo sapiens <400> 609 Cys Leu Ala Pro Leu Glu Gly Ala Arg 1 5 <210> 610 <211> 21 <212> PRT <213> Homo sapiens <400> 610 Thr Val Val Gln Pro Ser Val Gly Ala Ala Ala Gly Pro Val Val Pro 1 5 10 15 Pro Cys Pro Gly Arg 20 <210> 611 <211> 14 <212> PRT <213> Homo sapiens <400> 611 Glu His Ala Val Glu Gly Asp Cys Asp Phe Gln Leu Leu Lys 1 5 10 <210> 612 <211> 7 <212> PRT <213> Homo sapiens <400> 612 Phe Ser Val Val Tyr Ala Lys 1 5 <210> 613 <211> 10 <212> PRT <213> Homo sapiens <400> 613 His Thr Leu Asn Gln Ile Asp Glu Val Lys 1 5 10 <210> 614 <211> 11 <212> PRT <213> Homo sapiens <400> 614 Leu Asp Gly Lys Phe Ser Val Val Tyr Ala Lys 1 5 10 <210> 615 <211> 27 <212> PRT <213> Homo sapiens <400> 615 Tyr Asn Ile Leu Pro Glu Lys Glu Glu Phe Pro Phe Ala Leu Gly Val 1 5 10 15 Gln Thr Leu Pro Gln Thr Cys Asp Glu Pro Lys 20 25 <210> 616 <211> 14 <212> PRT <213> Homo sapiens <400> 616 Val Thr Gly Glu Gly Cys Val Tyr Leu Gln Thr Ser Leu Lys 1 5 10 <210> 617 <211> 12 <212> PRT <213> Homo sapiens <400> 617 Val Thr Ala Ala Pro Gln Ser Val Cys Ala Leu Arg 1 5 10 <210> 618 <211> 18 <212> PRT <213> Homo sapiens <400> 618 Val Ser Val Gln Leu Glu Ala Ser Pro Ala Phe Leu Ala Val Pro Val 1 5 10 15 Glu Lys <210> 619 <211> 11 <212> PRT <213> Homo sapiens <400> 619 Val Gly Phe Tyr Glu Ser Asp Val Met Gly Arg 1 5 10 <210> 620 <211> 16 <212> PRT <213> Homo sapiens <400> 620 Val Asp Ser His Phe Arg Gln Gly Ile Pro Phe Phe Gly Gln Val Arg 1 5 10 15 <210> 621 <211> 19 <212> PRT <213> Homo sapiens <400> 621 Val Asp Leu Ser Phe Ser Pro Ser Gln Ser Leu Pro Ala Ser His Ala 1 5 10 15 His Leu Arg <210> 622 <211> 14 <212> PRT <213> Homo sapiens <400> 622 Thr Glu Val Ser Ser Asn His Val Leu Ile Tyr Leu Asp Lys 1 5 10 <210> 623 <211> 22 <212> PRT <213> Homo sapiens <400> 623 Ser Leu Phe Thr Asp Leu Glu Ala Glu Asn Asp Val Leu His Cys Val 1 5 10 15 Ala Phe Ala Val Pro Lys 20 <210> 624 <211> 13 <212> PRT <213> Homo sapiens <400> 624 Ser Lys Ala Ile Gly Tyr Leu Asn Thr Gly Tyr Gln Arg 1 5 10 <210> 625 <211> 23 <212> PRT <213> Homo sapiens <400> 625 Gln Gln Asn Ala Gln Gly Gly Phe Ser Ser Thr Gln Asp Thr Val Val 1 5 10 15 Ala Leu His Ala Leu Ser Lys 20 <210> 626 <211> 17 <212> PRT <213> Homo sapiens <400> 626 Gln Leu Asn Tyr Lys His Tyr Asp Gly Ser Tyr Ser Thr Phe Gly Glu 1 5 10 15 Arg <210> 627 <211> 10 <212> PRT <213> Homo sapiens <400> 627 Gln Gly Ile Pro Phe Phe Gly Gln Val Arg 1 5 10 <210> 628 <211> 16 <212> PRT <213> Homo sapiens <400> 628 Gln Phe Ser Phe Pro Leu Ser Ser Glu Pro Phe Gln Gly Ser Tyr Lys 1 5 10 15 <210> 629 <211> 13 <212> PRT <213> Homo sapiens <400> 629 Asn Gln Gly Asn Thr Trp Leu Thr Ala Phe Val Leu Lys 1 5 10 <210> 630 <211> 12 <212> PRT <213> Homo sapiens <400> 630 Asn Glu Asp Ser Leu Val Phe Val Gln Thr Asp Lys 1 5 10 <210> 631 <211> 18 <212> PRT <213> Homo sapiens <400> 631 Leu Leu Ile Tyr Ala Val Leu Pro Thr Gly Asp Val Ile Gly Asp Ser 1 5 10 15 Ala Lys <210> 632 <211> 19 <212> PRT <213> Homo sapiens <400> 632 Leu His Thr Glu Ala Gln Ile Gln Glu Glu Gly Thr Val Val Glu Leu 1 5 10 15 Thr Gly Arg <210> 633 <211> 19 <212> PRT <213> Homo sapiens <400> 633 Lys Tyr Ser Asp Ala Ser Asp Cys His Gly Glu Asp Ser Gln Ala Phe 1 5 10 15 Cys Glu Lys <210> 634 <211> 14 <212> PRT <213> Homo sapiens <400> 634 Ile Ala Gln Trp Gln Ser Phe Gln Leu Glu Gly Gly Leu Lys 1 5 10 <210> 635 <211> 16 <212> PRT <213> Homo sapiens <400> 635 Phe Ser Gly Gln Leu Asn Ser His Gly Cys Phe Tyr Gln Gln Val Lys 1 5 10 15 <210> 636 <211> 9 <212> PRT <213> Homo sapiens <400> 636 Phe Glu Val Gln Val Thr Val Pro Lys 1 5 <210> 637 <211> 16 <212> PRT <213> Homo sapiens <400> 637 Asp Thr Val Ile Lys Pro Leu Leu Val Glu Pro Glu Gly Leu Glu Lys 1 5 10 15 <210> 638 <211> 15 <212> PRT <213> Homo sapiens <400> 638 Ala Leu Leu Ala Tyr Ala Phe Ala Leu Ala Gly Asn Gln Asp Lys 1 5 10 15 <210> 639 <211> 11 <212> PRT <213> Homo sapiens <400> 639 Ala Ile Gly Tyr Leu Asn Thr Gly Tyr Gln Arg 1 5 10 <210> 640 <211> 15 <212> PRT <213> Homo sapiens <400> 640 Ala Ala Gln Val Thr Ile Gln Ser Ser Gly Thr Phe Ser Ser Lys 1 5 10 15 <210> 641 <211> 12 <212> PRT <213> Homo sapiens <400> 641 Val Gly Trp Glu Gln Leu Leu Thr Thr Ile Ala Arg 1 5 10 <210> 642 <211> 12 <212> PRT <213> Homo sapiens <400> 642 Thr Ile Asn Glu Val Glu Asn Gln Ile Leu Thr Arg 1 5 10 <210> 643 <211> 13 <212> PRT <213> Homo sapiens <400> 643 Cys Gln Leu Glu Ile Asn Phe Asn Thr Leu Gln Thr Lys 1 5 10 <210> 644 <211> 16 <212> PRT <213> Homo sapiens <400> 644 Glu Thr Thr Asp Thr Asp Thr Ala Asp Gln Val Ile Ala Ser Phe Lys 1 5 10 15 <210> 645 <211> 11 <212> PRT <213> Homo sapiens <400> 645 Asp Tyr Glu Thr Ala Thr Leu Ser Asp Ile Lys 1 5 10 <210> 646 <211> 13 <212> PRT <213> Homo sapiens <400> 646 His Arg Asp Tyr Glu Thr Ala Thr Leu Ser Asp Ile Lys 1 5 10 <210> 647 <211> 26 <212> PRT <213> Homo sapiens <400> 647 Ile Ala Glu Ser Asn His Ile Lys Leu Ser Gly Ser Asn Pro Tyr Thr 1 5 10 15 Thr Val Thr Pro Gln Ile Ile Asn Ser Lys 20 25 <210> 648 <211> 15 <212> PRT <213> Homo sapiens <400> 648 Ile Cys Asp Gln Trp Asp Ala Leu Gly Ser Leu Thr His Ser Arg 1 5 10 15 <210> 649 <211> 17 <212> PRT <213> Homo sapiens <400> 649 Lys Asp Asp Pro Val Thr Asn Leu Asn Asn Ala Phe Glu Val Ala Glu 1 5 10 15 Lys <210> 650 <211> 10 <212> PRT <213> Homo sapiens <400> 650 Leu Ala Ser Asp Leu Leu Glu Trp Ile Arg 1 5 10 <210> 651 <211> 18 <212> PRT <213> Homo sapiens <400> 651 Leu Ser Gly Ser Asn Pro Tyr Thr Thr Val Thr Pro Gln Ile Ile Asn 1 5 10 15 Ser Lys <210> 652 <211> 21 <212> PRT <213> Homo sapiens <400> 652 Leu Ser Gly Ser Asn Pro Tyr Thr Thr Val Thr Pro Gln Ile Ile Asn 1 5 10 15 Ser Lys Trp Glu Lys 20 <210> 653 <211> 16 <212> PRT <213> Homo sapiens <400> 653 Gln Phe Ala Ser Gln Ala Asn Val Val Gly Pro Trp Ile Gln Thr Lys 1 5 10 15 <210> 654 <211> 10 <212> PRT <213> Homo sapiens <400> 654 Ser Thr Leu Pro Asp Ala Asp Arg Glu Arg 1 5 10 <210> 655 <211> 15 <212> PRT <213> Homo sapiens <400> 655 Val Leu Ala Gly Asp Lys Asn Phe Ile Thr Ala Glu Glu Leu Arg 1 5 10 15 <210> 656 <211> 13 <212> PRT <213> Homo sapiens <400> 656 Gly Asn Pro Thr Val Glu Val Asp Leu Phe Thr Ser Lys 1 5 10 <210> 657 <211> 8 <212> PRT <213> Homo sapiens <400> 657 Ser Cys Asn Cys Leu Leu Leu Lys 1 5 <210> 658 <211> 15 <212> PRT <213> Homo sapiens <400> 658 Val Asn Gln Ile Gly Ser Val Thr Glu Ser Leu Gln Ala Cys Lys 1 5 10 15 <210> 659 <211> 18 <212> PRT <213> Homo sapiens <400> 659 Ala Ala Val Pro Ser Gly Ala Ser Thr Gly Ile Tyr Glu Ala Leu Glu 1 5 10 15 Leu Arg <210> 660 <211> 12 <212> PRT <213> Homo sapiens <400> 660 Ala Gly Ala Val Glu Lys Gly Val Pro Leu Tyr Arg 1 5 10 <210> 661 <211> 7 <212> PRT <213> Homo sapiens <400> 661 Ala Val Glu His Ile Asn Lys 1 5 <210> 662 <211> 16 <212> PRT <213> Homo sapiens <400> 662 Ala Val Glu His Ile Asn Lys Thr Ile Ala Pro Ala Leu Val Ser Lys 1 5 10 15 <210> 663 <211> 19 <212> PRT <213> Homo sapiens <400> 663 Asp Ala Thr Asn Val Gly Asp Glu Gly Gly Phe Ala Pro Asn Ile Leu 1 5 10 15 Glu Asn Lys <210> 664 <211> 26 <212> PRT <213> Homo sapiens <400> 664 Asp Ala Thr Asn Val Gly Asp Glu Gly Gly Phe Ala Pro Asn Ile Leu 1 5 10 15 Glu Asn Lys Glu Gly Leu Glu Leu Leu Lys 20 25 <210> 665 <211> 19 <212> PRT <213> Homo sapiens <400> 665 Glu Ile Phe Asp Ser Arg Gly Asn Pro Thr Val Glu Val Asp Leu Phe 1 5 10 15 Thr Ser Lys <210> 666 <211> 23 <212> PRT <213> Homo sapiens <400> 666 Glu Ile Phe Asp Ser Arg Gly Asn Pro Thr Val Glu Val Asp Leu Phe 1 5 10 15 Thr Ser Lys Gly Leu Phe Arg 20 <210> 667 <211> 24 <212> PRT <213> Homo sapiens <400> 667 Glu Lys Tyr Gly Lys Asp Ala Thr Asn Val Gly Asp Glu Gly Gly Phe 1 5 10 15 Ala Pro Asn Ile Leu Glu Asn Lys 20 <210> 668 <211> 21 <212> PRT <213> Homo sapiens <400> 668 Phe Thr Ala Ser Ala Gly Ile Gln Val Val Gly Asp Asp Leu Thr Val 1 5 10 15 Thr Asn Pro Lys Arg 20 <210> 669 <211> 30 <212> PRT <213> Homo sapiens <400> 669 His Ile Ala Asp Leu Ala Gly Asn Ser Glu Val Ile Leu Pro Val Pro 1 5 10 15 Ala Phe Asn Val Ile Asn Gly Gly Ser His Ala Gly Asn Lys 20 25 30 <210> 670 <211> 8 <212> PRT <213> Homo sapiens <400> 670 Ile Glu Glu Glu Leu Gly Ser Lys 1 5 <210> 671 <211> 10 <212> PRT <213> Homo sapiens <400> 671 Ile Glu Glu Glu Leu Gly Ser Lys Ala Lys 1 5 10 <210> 672 <211> 14 <212> PRT <213> Homo sapiens <400> 672 Ile Glu Glu Glu Leu Gly Ser Lys Ala Lys Phe Ala Gly Arg 1 5 10 <210> 673 <211> 10 <212> PRT <213> Homo sapiens <400> 673 Ile Gly Ala Glu Val Tyr His Asn Leu Lys 1 5 10 <210> 674 <211> 14 <212> PRT <213> Homo sapiens <400> 674 Ile Gly Ala Glu Val Tyr His Asn Leu Lys Asn Val Ile Lys 1 5 10 <210> 675 <211> 9 <212> PRT <213> Homo sapiens <400> 675 Lys Leu Asn Val Thr Glu Gln Glu Lys 1 5 <210> 676 <211> 12 <212> PRT <213> Homo sapiens <400> 676 Lys Leu Asn Val Thr Glu Gln Glu Lys Ile Asp Lys 1 5 10 <210> 677 <211> 14 <212> PRT <213> Homo sapiens <400> 677 Leu Ala Gln Ala Asn Gly Trp Gly Val Met Val Ser His Arg 1 5 10 <210> 678 <211> 8 <212> PRT <213> Homo sapiens <400> 678 Asn Phe Arg Asn Pro Leu Ala Lys 1 5 <210> 679 <211> 22 <212> PRT <213> Homo sapiens <400> 679 Ser Gly Glu Thr Glu Asp Thr Phe Ile Ala Asp Leu Val Val Gly Leu 1 5 10 15 Cys Thr Gly Gln Ile Lys 20 <210> 680 <211> 16 <212> PRT <213> Homo sapiens <400> 680 Ser Gly Lys Tyr Asp Leu Asp Phe Lys Ser Pro Asp Asp Pro Ser Arg 1 5 10 15 <210> 681 <211> 8 <212> PRT <213> Homo sapiens <400> 681 Ser Ile Leu Lys Ile His Ala Arg 1 5 <210> 682 <211> 19 <212> PRT <213> Homo sapiens <400> 682 Ser Pro Asp Asp Pro Ser Arg Tyr Ile Ser Pro Asp Gln Leu Ala Asp 1 5 10 15 Leu Tyr Lys <210> 683 <211> 9 <212> PRT <213> Homo sapiens <400> 683 Thr Ile Ala Pro Ala Leu Val Ser Lys 1 5 <210> 684 <211> 22 <212> PRT <213> Homo sapiens <400> 684 Tyr Gly Lys Asp Ala Thr Asn Val Gly Asp Glu Gly Gly Phe Ala Pro 1 5 10 15 Asn Ile Leu Glu Asn Lys 20 <210> 685 <211> 29 <212> PRT <213> Homo sapiens <400> 685 Tyr Gly Lys Asp Ala Thr Asn Val Gly Asp Glu Gly Gly Phe Ala Pro 1 5 10 15 Asn Ile Leu Glu Asn Lys Glu Gly Leu Glu Leu Leu Lys 20 25 <210> 686 <211> 12 <212> PRT <213> Homo sapiens <400> 686 Tyr Ile Ser Pro Asp Gln Leu Ala Asp Leu Tyr Lys 1 5 10 <210> 687 <211> 6 <212> PRT <213> Homo sapiens <400> 687 Tyr Asn Gln Leu Leu Arg 1 5 <210> 688 <211> 14 <212> PRT <213> Homo sapiens <400> 688 Tyr Asn Gln Leu Leu Arg Ile Glu Glu Glu Leu Gly Ser Lys 1 5 10 <210> 689 <211> 16 <212> PRT <213> Homo sapiens <400> 689 Tyr Asn Gln Leu Leu Arg Ile Glu Glu Glu Leu Gly Ser Lys Ala Lys 1 5 10 15 <210> 690 <211> 13 <212> PRT <213> Homo sapiens <400> 690 Tyr Asp Leu Asp Phe Lys Ser Pro Asp Asp Pro Ser Arg 1 5 10 <210> 691 <211> 17 <212> PRT <213> Homo sapiens <400> 691 Val Leu Ser Ala Leu Gln Ala Val Gln Gly Leu Leu Val Ala Gln Gly 1 5 10 15 Arg <210> 692 <211> 13 <212> PRT <213> Homo sapiens <400> 692 Ser Leu Asp Phe Thr Glu Leu Asp Val Ala Ala Glu Lys 1 5 10 <210> 693 <211> 17 <212> PRT <213> Homo sapiens <400> 693 Val Leu Ser Ala Leu Gln Ala Val Gln Gly Leu Leu Val Ala Gln Gly 1 5 10 15 Arg <210> 694 <211> 19 <212> PRT <213> Homo sapiens <400> 694 Ala Asn Ala Gly Lys Pro Lys Asp Pro Thr Phe Ile Pro Ala Pro Ile 1 5 10 15 Gln Ala Lys <210> 695 <211> 10 <212> PRT <213> Homo sapiens <400> 695 Ala Leu Leu Leu Leu Cys Gly Glu Asp Asp 1 5 10 <210> 696 <211> 17 <212> PRT <213> Homo sapiens <400> 696 Ala Gln Val Leu Arg Gly Thr Val Thr Asp Phe Pro Gly Phe Asp Glu 1 5 10 15 Arg <210> 697 <211> 13 <212> PRT <213> Homo sapiens <400> 697 Asp Leu Leu Asp Asp Leu Lys Ser Glu Leu Thr Gly Lys 1 5 10 <210> 698 <211> 16 <212> PRT <213> Homo sapiens <400> 698 Asp Leu Leu Asp Asp Leu Lys Ser Glu Leu Thr Gly Lys Phe Glu Lys 1 5 10 15 <210> 699 <211> 16 <212> PRT <213> Homo sapiens <400> 699 Gly Leu Gly Thr Asp Glu Glu Ser Ile Leu Thr Leu Leu Thr Ser Arg 1 5 10 15 <210> 700 <211> 20 <212> PRT <213> Homo sapiens <400> 700 Gly Thr Val Thr Asp Phe Pro Gly Phe Asp Glu Arg Ala Asp Ala Glu 1 5 10 15 Thr Leu Arg Lys 20 <210> 701 <211> 11 <212> PRT <213> Homo sapiens <400> 701 Asn Phe Ala Thr Ser Leu Tyr Ser Met Ile Lys 1 5 10 <210> 702 <211> 9 <212> PRT <213> Homo sapiens <400> 702 Ser Glu Ile Asp Leu Phe Asn Ile Arg 1 5 <210> 703 <211> 9 <212> PRT <213> Homo sapiens <400> 703 Val Leu Thr Glu Ile Ile Ala Ser Arg 1 5 <210> 704 <211> 15 <212> PRT <213> Homo sapiens <400> 704 Trp Gly Thr Asp Glu Glu Lys Phe Ile Thr Ile Phe Gly Thr Arg 1 5 10 15 <210> 705 <211> 12 <212> PRT <213> Homo sapiens <400> 705 Gly Thr Val Thr Asp Phe Pro Gly Phe Asp Glu Arg 1 5 10 <210> 706 <211> 10 <212> PRT <213> Homo sapiens <400> 706 Val Phe Ala Glu Asn Lys Glu Ile Gln Lys 1 5 10 <210> 707 <211> 18 <212> PRT <213> Homo sapiens <400> 707 Leu Tyr Ala Tyr Glu Pro Ala Asp Thr Ala Leu Leu Leu Asp Asn Met 1 5 10 15 Lys Lys <210> 708 <211> 7 <212> PRT <213> Homo sapiens <400> 708 Leu Pro Gln Thr Leu Ser Arg 1 5 <210> 709 <211> 28 <212> PRT <213> Homo sapiens <400> 709 Leu Ala Glu Gln Phe Val Leu Leu Asn Leu Val Tyr Glu Thr Thr Asp 1 5 10 15 Lys His Leu Ser Pro Asp Gly Gln Tyr Val Pro Arg 20 25 <210> 710 <211> 17 <212> PRT <213> Homo sapiens <400> 710 Leu Ala Glu Gln Phe Val Leu Leu Asn Leu Val Tyr Glu Thr Thr Asp 1 5 10 15 Lys <210> 711 <211> 11 <212> PRT <213> Homo sapiens <400> 711 Ile Met Phe Val Asp Pro Ser Leu Thr Val Arg 1 5 10 <210> 712 <211> 12 <212> PRT <213> Homo sapiens <400> 712 Asp Ser Arg Pro Lys Leu Pro Gln Thr Leu Ser Arg 1 5 10 <210> 713 <211> 10 <212> PRT <213> Homo sapiens <400> 713 Ala Asn Arg Pro Phe Leu Val Phe Ile Arg 1 5 10 <210> 714 <211> 17 <212> PRT <213> Homo sapiens <400> 714 Ala Thr Glu Asp Glu Gly Ser Glu Gln Lys Ile Pro Glu Ala Thr Asn 1 5 10 15 Arg <210> 715 <211> 18 <212> PRT <213> Homo sapiens <400> 715 Ala Thr Glu Asp Glu Gly Ser Glu Gln Lys Ile Pro Glu Ala Thr Asn 1 5 10 15 Arg Arg <210> 716 <211> 12 <212> PRT <213> Homo sapiens <400> 716 Glu Val Pro Leu Asn Thr Ile Ile Phe Met Gly Arg 1 5 10 <210> 717 <211> 10 <212> PRT <213> Homo sapiens <400> 717 Phe Arg Ile Glu Asp Gly Phe Ser Leu Lys 1 5 10 <210> 718 <211> 25 <212> PRT <213> Homo sapiens <400> 718 Ile Thr Asp Val Ile Pro Ser Glu Ala Ile Asn Glu Leu Thr Val Leu 1 5 10 15 Val Leu Val Asn Thr Ile Tyr Phe Lys 20 25 <210> 719 <211> 18 <212> PRT <213> Homo sapiens <400> 719 Lys Ala Thr Glu Asp Glu Gly Ser Glu Gln Lys Ile Pro Glu Ala Thr 1 5 10 15 Asn Arg <210> 720 <211> 10 <212> PRT <213> Homo sapiens <400> 720 Ser Lys Phe Ser Pro Glu Asn Thr Arg Lys 1 5 10 <210> 721 <211> 22 <212> PRT <213> Homo sapiens <400> 721 Ser Lys Leu Pro Gly Ile Val Ala Glu Gly Arg Asp Asp Leu Tyr Val 1 5 10 15 Ser Asp Ala Phe His Lys 20 <210> 722 <211> 11 <212> PRT <213> Homo sapiens <400> 722 Thr Ser Asp Gln Ile His Phe Phe Phe Ala Lys 1 5 10 <210> 723 <211> 8 <212> PRT <213> Homo sapiens <400> 723 Ala Glu Leu Gln Glu Gly Ala Arg 1 5 <210> 724 <211> 18 <212> PRT <213> Homo sapiens <400> 724 Ala His Val Asp Ala Leu Arg Thr His Leu Ala Pro Tyr Ser Asp Glu 1 5 10 15 Leu Arg <210> 725 <211> 11 <212> PRT <213> Homo sapiens <400> 725 Ala Thr Glu His Leu Ser Thr Leu Ser Glu Lys 1 5 10 <210> 726 <211> 11 <212> PRT <213> Homo sapiens <400> 726 Asp Leu Ala Thr Val Tyr Val Asp Val Leu Lys 1 5 10 <210> 727 <211> 17 <212> PRT <213> Homo sapiens <400> 727 Asp Ser Gly Arg Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala Leu Gly 1 5 10 15 Lys <210> 728 <211> 13 <212> PRT <213> Homo sapiens <400> 728 Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala Leu Gly Lys 1 5 10 <210> 729 <211> 16 <212> PRT <213> Homo sapiens <400> 729 Glu Gln Leu Gly Pro Val Thr Gln Glu Phe Trp Asp Asn Leu Glu Lys 1 5 10 15 <210> 730 <211> 18 <212> PRT <213> Homo sapiens <400> 730 Leu Ala Glu Tyr His Ala Lys Ala Thr Glu His Leu Ser Thr Leu Ser 1 5 10 15 Glu Lys <210> 731 <211> 11 <212> PRT <213> Homo sapiens <400> 731 Leu Glu Ala Leu Lys Glu Asn Gly Gly Ala Arg 1 5 10 <210> 732 <211> 7 <212> PRT <213> Homo sapiens <400> 732 Leu His Glu Leu Gln Glu Lys 1 5 <210> 733 <211> 14 <212> PRT <213> Homo sapiens <400> 733 Leu Leu Asp Asn Trp Asp Ser Val Thr Ser Thr Phe Ser Lys 1 5 10 <210> 734 <211> 18 <212> PRT <213> Homo sapiens <400> 734 Leu Arg Glu Gln Leu Gly Pro Val Thr Gln Glu Phe Trp Asp Asn Leu 1 5 10 15 Glu Lys <210> 735 <211> 11 <212> PRT <213> Homo sapiens <400> 735 Gln Gly Leu Leu Pro Val Leu Glu Ser Phe Lys 1 5 10 <210> 736 <211> 15 <212> PRT <213> Homo sapiens <400> 736 Gln Lys Val Glu Pro Leu Arg Ala Glu Leu Gln Glu Gly Ala Arg 1 5 10 15 <210> 737 <211> 11 <212> PRT <213> Homo sapiens <400> 737 Thr His Leu Ala Pro Tyr Ser Asp Glu Leu Arg 1 5 10 <210> 738 <211> 13 <212> PRT <213> Homo sapiens <400> 738 Thr His Leu Ala Pro Tyr Ser Asp Glu Leu Arg Gln Arg 1 5 10 <210> 739 <211> 13 <212> PRT <213> Homo sapiens <400> 739 Val Glu Pro Leu Arg Ala Glu Leu Gln Glu Gly Ala Arg 1 5 10 <210> 740 <211> 13 <212> PRT <213> Homo sapiens <400> 740 Val Lys Asp Leu Ala Thr Val Tyr Val Asp Val Leu Lys 1 5 10 <210> 741 <211> 11 <212> PRT <213> Homo sapiens <400> 741 Val Gln Pro Tyr Leu Asp Asp Phe Gln Lys Lys 1 5 10 <210> 742 <211> 12 <212> PRT <213> Homo sapiens <400> 742 Val Ser Phe Leu Ser Ala Leu Glu Glu Tyr Thr Lys 1 5 10 <210> 743 <211> 13 <212> PRT <213> Homo sapiens <400> 743 Val Ser Phe Leu Ser Ala Leu Glu Glu Tyr Thr Lys Lys 1 5 10 <210> 744 <211> 11 <212> PRT <213> Homo sapiens <400> 744 Val Lys Ser Pro Glu Leu Gln Ala Glu Ala Lys 1 5 10 <210> 745 <211> 9 <212> PRT <213> Homo sapiens <400> 745 Ser Pro Glu Leu Gln Ala Glu Ala Lys 1 5 <210> 746 <211> 11 <212> PRT <213> Homo sapiens <400> 746 Ser Lys Glu Gln Leu Thr Pro Leu Ile Lys Lys 1 5 10 <210> 747 <211> 10 <212> PRT <213> Homo sapiens <400> 747 Ser Lys Glu Gln Leu Thr Pro Leu Ile Lys 1 5 10 <210> 748 <211> 22 <212> PRT <213> Homo sapiens <400> 748 Ala Gly Thr Glu Leu Val Asn Phe Leu Ser Tyr Phe Val Glu Leu Gly 1 5 10 15 Thr Gln Pro Ala Thr Gln 20 <210> 749 <211> 9 <212> PRT <213> Homo sapiens <400> 749 Ile Ser Ala Ser Ala Glu Glu Leu Arg 1 5 <210> 750 <211> 13 <212> PRT <213> Homo sapiens <400> 750 Leu Gly Glu Val Asn Thr Tyr Ala Gly Asp Leu Gln Lys 1 5 10 <210> 751 <211> 14 <212> PRT <213> Homo sapiens <400> 751 Ser Glu Leu Thr Gln Gln Leu Asn Ala Leu Phe Gln Asp Lys 1 5 10 <210> 752 <211> 17 <212> PRT <213> Homo sapiens <400> 752 Ser Leu Ala Glu Leu Gly Gly His Leu Asp Gln Gln Val Glu Glu Phe 1 5 10 15 Arg <210> 753 <211> 21 <212> PRT <213> Homo sapiens <400> 753 Ala Thr Phe Gly Cys His Asp Gly Tyr Ser Leu Asp Gly Pro Glu Glu 1 5 10 15 Ile Glu Cys Thr Lys 20 <210> 754 <211> 9 <212> PRT <213> Homo sapiens <400> 754 Ala Thr Val Val Tyr Gln Gly Glu Arg 1 5 <210> 755 <211> 12 <212> PRT <213> Homo sapiens <400> 755 Cys Phe Lys Glu His Ser Ser Leu Ala Phe Trp Lys 1 5 10 <210> 756 <211> 15 <212> PRT <213> Homo sapiens <400> 756 Phe Ile Cys Pro Leu Thr Gly Leu Trp Pro Ile Asn Thr Leu Lys 1 5 10 15 <210> 757 <211> 19 <212> PRT <213> Homo sapiens <400> 757 Lys Cys Ser Tyr Thr Glu Asp Ala Gln Cys Ile Asp Gly Thr Ile Glu 1 5 10 15 Val Pro Lys <210> 758 <211> 17 <212> PRT <213> Homo sapiens <400> 758 Thr Cys Pro Lys Pro Asp Asp Leu Pro Phe Ser Thr Val Val Pro Leu 1 5 10 15 Lys <210> 759 <211> 9 <212> PRT <213> Homo sapiens <400> 759 Thr Asp Ala Ser Asp Val Lys Pro Cys 1 5 <210> 760 <211> 14 <212> PRT <213> Homo sapiens <400> 760 Val Cys Pro Phe Ala Gly Ile Leu Glu Asn Gly Ala Val Arg 1 5 10 <210> 761 <211> 21 <212> PRT <213> Homo sapiens <400> 761 Ser Asp Gly Ala Pro Ala Ser Asp Ser Lys Pro Gly Ser Ser Glu Ala 1 5 10 15 Ala Pro Ser Ser Lys 20 <210> 762 <211> 14 <212> PRT <213> Homo sapiens <400> 762 Glu Thr Pro Ala Ala Thr Glu Ala Pro Ser Ser Thr Pro Lys 1 5 10 <210> 763 <211> 24 <212> PRT <213> Homo sapiens <400> 763 Ala Glu Pro Pro Lys Ala Pro Glu Gln Glu Gln Ala Ala Pro Gly Pro 1 5 10 15 Ala Ala Gly Gly Glu Ala Pro Lys 20 <210> 764 <211> 23 <212> PRT <213> Homo sapiens <400> 764 Ala Phe Ser Ala Val Asp Thr Asp Gly Asn Gly Thr Ile Asn Ala Gln 1 5 10 15 Glu Leu Gly Ala Ala Leu Lys 20 <210> 765 <211> 13 <212> PRT <213> Homo sapiens <400> 765 Ala Gly Glu Leu Thr Pro Glu Glu Glu Ala Gln Tyr Lys 1 5 10 <210> 766 <211> 11 <212> PRT <213> Homo sapiens <400> 766 Ala Gly Leu Glu Asp Leu Gln Val Ala Phe Arg 1 5 10 <210> 767 <211> 17 <212> PRT <213> Homo sapiens <400> 767 Glu Ala Asp Val Asp Gln Asp Gly Arg Val Asn Tyr Glu Glu Phe Ala 1 5 10 15 Arg <210> 768 <211> 10 <212> PRT <213> Homo sapiens <400> 768 Tyr Leu Gly Gln Asp Tyr Glu Gln Leu Arg 1 5 10 <210> 769 <211> 11 <212> PRT <213> Homo sapiens <400> 769 Trp Asn Thr Thr Leu Tyr Glu Gly Thr Trp Arg 1 5 10 <210> 770 <211> 18 <212> PRT <213> Homo sapiens <400> 770 Arg Pro Thr Glu Leu Leu Ser Asn Pro Gln Phe Ile Val Asp Gly Ala 1 5 10 15 Thr Arg <210> 771 <211> 13 <212> PRT <213> Homo sapiens <400> 771 Asn Tyr Pro Ala Thr Phe Trp Val Asn Pro Gln Phe Lys 1 5 10 <210> 772 <211> 24 <212> PRT <213> Homo sapiens <400> 772 Leu Pro Pro Gly Glu Tyr Val Val Val Pro Ser Thr Phe Glu Pro Asn 1 5 10 15 Lys Glu Gly Asp Phe Val Leu Arg 20 <210> 773 <211> 12 <212> PRT <213> Homo sapiens <400> 773 Leu Glu Ile Cys Asn Leu Thr Pro Asp Ala Leu Lys 1 5 10 <210> 774 <211> 9 <212> PRT <213> Homo sapiens <400> 774 Asp Phe Phe Leu Ala Asn Ala Ser Arg 1 5 <210> 775 <211> 11 <212> PRT <213> Homo sapiens <400> 775 Ala Pro Ser Asp Leu Tyr Gln Ile Ile Leu Lys 1 5 10 <210> 776 <211> 13 <212> PRT <213> Homo sapiens <400> 776 Ala Ala Ala Pro Ala Pro Val Ser Glu Ala Val Cys Arg 1 5 10 <210> 777 <211> 13 <212> PRT <213> Homo sapiens <400> 777 Cys Gly Glu Asp Asp Glu Thr Ile Pro Ser Glu Tyr Arg 1 5 10 <210> 778 <211> 16 <212> PRT <213> Homo sapiens <400> 778 Glu Glu Ser Thr Glu Val Leu Lys Ala Gln Ser Ala Gly Thr Val Arg 1 5 10 15 <210> 779 <211> 9 <212> PRT <213> Homo sapiens <400> 779 Gln Ala Glu Pro Glu Leu Asp Leu Arg 1 5 <210> 780 <211> 15 <212> PRT <213> Homo sapiens <400> 780 Ser Glu Ser Glu Leu Ile Asp Glu Leu Ser Glu Asp Phe Asp Arg 1 5 10 15 <210> 781 <211> 19 <212> PRT <213> Homo sapiens <400> 781 Ser Glu Ser Glu Leu Ile Asp Glu Leu Ser Glu Asp Phe Asp Arg Ser 1 5 10 15 Glu Cys Lys <210> 782 <211> 15 <212> PRT <213> Homo sapiens <400> 782 Ile Lys Asp Pro Asp Ala Ser Lys Pro Glu Asp Trp Asp Glu Arg 1 5 10 15 <210> 783 <211> 22 <212> PRT <213> Homo sapiens <400> 783 Ile Asp Asn Ser Gln Val Glu Ser Gly Ser Leu Glu Asp Asp Trp Asp 1 5 10 15 Phe Leu Pro Pro Lys Lys 20 <210> 784 <211> 18 <212> PRT <213> Homo sapiens <400> 784 Phe Tyr Gly Asp Glu Glu Lys Asp Lys Gly Leu Gln Thr Ser Gln Asp 1 5 10 15 Ala Arg <210> 785 <211> 12 <212> PRT <213> Homo sapiens <400> 785 Glu Gln Phe Leu Asp Gly Asp Gly Trp Thr Ser Arg 1 5 10 <210> 786 <211> 14 <212> PRT <213> Homo sapiens <400> 786 Phe Tyr Ala Leu Ser Ala Ser Phe Glu Pro Phe Ser Asn Lys 1 5 10 <210> 787 <211> 10 <212> PRT <213> Homo sapiens <400> 787 Glu Gln Trp Pro Gln Cys Pro Thr Ile Lys 1 5 10 <210> 788 <211> 17 <212> PRT <213> Homo sapiens <400> 788 Gly Gln Asp His Cys Gly Ile Glu Ser Glu Val Val Ala Gly Ile Pro 1 5 10 15 Arg <210> 789 <211> 11 <212> PRT <213> Homo sapiens <400> 789 Ile Cys Glu Pro Gly Tyr Ser Pro Thr Tyr Lys 1 5 10 <210> 790 <211> 14 <212> PRT <213> Homo sapiens <400> 790 Ile Cys Glu Pro Gly Tyr Ser Pro Thr Tyr Lys Gln Asp Lys 1 5 10 <210> 791 <211> 19 <212> PRT <213> Homo sapiens <400> 791 Ile Leu Arg Gly Gln Asp His Cys Gly Ile Glu Ser Glu Val Val Ala 1 5 10 15 Gly Ile Pro <210> 792 <211> 14 <212> PRT <213> Homo sapiens <400> 792 Leu Cys Gly Thr Phe Leu Gly Gly Pro Lys Pro Pro Gln Arg 1 5 10 <210> 793 <211> 8 <212> PRT <213> Homo sapiens <400> 793 Thr Asp Gln Tyr Trp Glu Lys Ile 1 5 <210> 794 <211> 10 <212> PRT <213> Homo sapiens <400> 794 Tyr Val Glu Cys Ser Ala Leu Thr Gln Lys 1 5 10 <210> 795 <211> 17 <212> PRT <213> Homo sapiens <400> 795 Asn Val Phe Asp Glu Ala Ile Leu Ala Ala Leu Glu Pro Pro Glu Pro 1 5 10 15 Lys <210> 796 <211> 20 <212> PRT <213> Homo sapiens <400> 796 Gly Leu Lys Asn Val Phe Asp Glu Ala Ile Leu Ala Ala Leu Glu Pro 1 5 10 15 Pro Glu Pro Lys 20 <210> 797 <211> 21 <212> PRT <213> Homo sapiens <400> 797 Ala Asp Phe Asp Asn Thr Val Ala Ile His Pro Thr Ser Ser Glu Glu 1 5 10 15 Leu Val Thr Leu Arg 20 <210> 798 <211> 12 <212> PRT <213> Homo sapiens <400> 798 Ala Leu Leu Thr Pro Val Ala Ile Ala Ala Gly Arg 1 5 10 <210> 799 <211> 18 <212> PRT <213> Homo sapiens <400> 799 Gly His Ala Ala Phe Thr Ser Asp Pro Lys Pro Thr Ile Glu Val Ser 1 5 10 15 Gly Lys <210> 800 <211> 11 <212> PRT <213> Homo sapiens <400> 800 Gly Ile Tyr Ala Val Gly Asp Val Cys Gly Lys 1 5 10 <210> 801 <211> 13 <212> PRT <213> Homo sapiens <400> 801 Leu Gly Gly Thr Cys Val Asn Val Gly Cys Val Pro Lys 1 5 10 <210> 802 <211> 22 <212> PRT <213> Homo sapiens <400> 802 Leu Gly Ile Gln Thr Asp Asp Lys Gly His Ile Ile Val Asp Glu Phe 1 5 10 15 Gln Asn Thr Asn Val Lys 20 <210> 803 <211> 11 <212> PRT <213> Homo sapiens <400> 803 Leu Asn Ala Ile Tyr Gln Asn Asn Leu Thr Lys 1 5 10 <210> 804 <211> 10 <212> PRT <213> Homo sapiens <400> 804 Val Ser Glu Glu Ile Glu Asp Ile Ile Lys 1 5 10 <210> 805 <211> 11 <212> PRT <213> Homo sapiens <400> 805 Asn Pro Ser Ala Ala Phe Phe Cys Val Ala Arg 1 5 10 <210> 806 <211> 14 <212> PRT <213> Homo sapiens <400> 806 Leu Gln Asp Phe Lys Leu Asp Phe Gly Asn Ser Gln Gly Lys 1 5 10 <210> 807 <211> 14 <212> PRT <213> Homo sapiens <400> 807 Glu Leu Ser Glu Ala Leu Gly Gln Ile Phe Asp Ser Gln Arg 1 5 10 <210> 808 <211> 11 <212> PRT <213> Homo sapiens <400> 808 Leu Ala Asp Gly Gly Ala Thr Asn Gln Gly Arg 1 5 10 <210> 809 <211> 13 <212> PRT <213> Homo sapiens <400> 809 Ser Asp Leu Ala Val Pro Ser Glu Leu Ala Leu Leu Lys 1 5 10 <210> 810 <211> 16 <212> PRT <213> Homo sapiens <400> 810 Ser Thr Ser Ser Phe Pro Cys Pro Ala Gly His Phe Asn Gly Phe Arg 1 5 10 15 <210> 811 <211> 17 <212> PRT <213> Homo sapiens <400> 811 Thr Leu Gln Ala Leu Glu Phe His Thr Val Pro Phe Gln Leu Leu Ala 1 5 10 15 Arg <210> 812 <211> 13 <212> PRT <213> Homo sapiens <400> 812 Tyr Ser Ser Asp Tyr Phe Gln Ala Pro Ser Asp Tyr Arg 1 5 10 <210> 813 <211> 19 <212> PRT <213> Homo sapiens <400> 813 Cys Leu Thr Thr Asp Glu Tyr Asp Gly His Ser Thr Tyr Pro Ser His 1 5 10 15 Gln Tyr Gln <210> 814 <211> 10 <212> PRT <213> Homo sapiens <400> 814 Leu Gln Ala Val Thr Asp Asp His Ile Arg 1 5 10 <210> 815 <211> 12 <212> PRT <213> Homo sapiens <400> 815 Val Thr Asp Ser Ser Val Ser Val Gln Leu Arg Glu 1 5 10 <210> 816 <211> 14 <212> PRT <213> Homo sapiens <400> 816 Thr Arg Val Thr Asp Ser Ser Val Ser Val Gln Leu Arg Glu 1 5 10 <210> 817 <211> 30 <212> PRT <213> Homo sapiens <400> 817 Ser Pro Asn Pro Glu Gly Ile Asn Ile Tyr Glu Pro Ala Pro Pro Thr 1 5 10 15 Gly Pro Thr Gln Arg Pro Leu Glu Thr Leu Gly Asn Phe Arg 20 25 30 <210> 818 <211> 19 <212> PRT <213> Homo sapiens <400> 818 Gln Leu Leu Leu Glu Glu Trp Gly Pro Leu Ser Gly Gly Leu Glu Leu 1 5 10 15 Pro Gln Arg <210> 819 <211> 15 <212> PRT <213> Homo sapiens <400> 819 Tyr Gly Thr Cys Ile Tyr Gln Gly Arg Leu Trp Ala Phe Cys Cys 1 5 10 15 <210> 820 <211> 9 <212> PRT <213> Homo sapiens <400> 820 Tyr Gly Thr Cys Ile Tyr Gln Gly Arg 1 5 <210> 821 <211> 10 <212> PRT <213> Homo sapiens <400> 821 Arg Tyr Gly Thr Cys Ile Tyr Gln Gly Arg 1 5 10 <210> 822 <211> 6 <212> PRT <213> Homo sapiens <400> 822 Leu Trp Ala Phe Cys Cys 1 5 <210> 823 <211> 10 <212> PRT <213> Homo sapiens <400> 823 Ile Pro Ala Cys Ile Ala Gly Glu Arg Arg 1 5 10 <210> 824 <211> 9 <212> PRT <213> Homo sapiens <400> 824 Ile Pro Ala Cys Ile Ala Gly Glu Arg 1 5 <210> 825 <211> 11 <212> PRT <213> Homo sapiens <400> 825 Ala Leu His Phe Ala Ile Ser Glu Tyr Asn Lys 1 5 10 <210> 826 <211> 14 <212> PRT <213> Homo sapiens <400> 826 Ala Leu His Phe Ala Ile Ser Glu Tyr Asn Lys Ala Thr Lys 1 5 10 <210> 827 <211> 19 <212> PRT <213> Homo sapiens <400> 827 Ala Arg Gln Gln Thr Val Gly Gly Val Asn Tyr Phe Phe Asp Val Glu 1 5 10 15 Val Gly Arg <210> 828 <211> 8 <212> PRT <213> Homo sapiens <400> 828 Ala Thr Lys Asp Asp Tyr Tyr Arg 1 5 <210> 829 <211> 22 <212> PRT <213> Homo sapiens <400> 829 Glu Glu Asp Arg Ile Ile Pro Gly Gly Ile Tyr Asn Ala Asp Leu Asn 1 5 10 15 Asp Glu Trp Val Gln Arg 20 <210> 830 <211> 17 <212> PRT <213> Homo sapiens <400> 830 Lys Gln Leu Cys Ser Phe Glu Ile Tyr Glu Val Pro Trp Glu Asn Arg 1 5 10 15 Arg <210> 831 <211> 15 <212> PRT <213> Homo sapiens <400> 831 Gln Leu Cys Ser Phe Glu Ile Tyr Glu Val Pro Trp Glu Asn Arg 1 5 10 15 <210> 832 <211> 16 <212> PRT <213> Homo sapiens <400> 832 Gln Leu Cys Ser Phe Glu Ile Tyr Glu Val Pro Trp Glu Asn Arg Arg 1 5 10 15 <210> 833 <211> 17 <212> PRT <213> Homo sapiens <400> 833 Gln Gln Thr Val Gly Gly Val Asn Tyr Phe Phe Asp Val Glu Val Gly 1 5 10 15 Arg <210> 834 <211> 10 <212> PRT <213> Homo sapiens <400> 834 Ser Leu Val Lys Ser Arg Cys Gln Glu Ser 1 5 10 <210> 835 <211> 18 <212> PRT <213> Homo sapiens <400> 835 Ser Gln Pro Asn Leu Asp Thr Cys Ala Phe His Glu Gln Pro Glu Leu 1 5 10 15 Gln Lys <210> 836 <211> 19 <212> PRT <213> Homo sapiens <400> 836 Ser Gln Pro Asn Leu Asp Thr Cys Ala Phe His Glu Gln Pro Glu Leu 1 5 10 15 Gln Lys Lys <210> 837 <211> 18 <212> PRT <213> Homo sapiens <400> 837 Ile Ile Pro Gly Gly Ile Tyr Asn Ala Asp Leu Asn Asp Glu Trp Val 1 5 10 15 Gln Arg <210> 838 <211> 16 <212> PRT <213> Homo sapiens <400> 838 Val Ser Gln Thr Thr Trp Asp Ser Gly Phe Cys Ala Val Asn Pro Lys 1 5 10 15 <210> 839 <211> 11 <212> PRT <213> Homo sapiens <400> 839 Lys Leu Gln Ala Thr Val Gln Glu Leu Gln Lys 1 5 10 <210> 840 <211> 10 <212> PRT <213> Homo sapiens <400> 840 Asp Ala Gly Pro Leu Leu Ile Ser Leu Lys 1 5 10 <210> 841 <211> 9 <212> PRT <213> Homo sapiens <400> 841 Ala Asp Gln Cys Tyr Glu Asp Val Arg 1 5 <210> 842 <211> 16 <212> PRT <213> Homo sapiens <400> 842 Ala Ala Pro Glu Ala Ser Gly Thr Pro Ser Ser Asp Ala Val Ser Arg 1 5 10 15 <210> 843 <211> 13 <212> PRT <213> Homo sapiens <400> 843 Ala Ala Val Tyr His His Phe Ile Ser Asp Gly Val Arg 1 5 10 <210> 844 <211> 14 <212> PRT <213> Homo sapiens <400> 844 Ala Ala Val Tyr His His Phe Ile Ser Asp Gly Val Arg Lys 1 5 10 <210> 845 <211> 11 <212> PRT <213> Homo sapiens <400> 845 Ala Cys Glu Pro Gly Val Asp Tyr Val Tyr Lys 1 5 10 <210> 846 <211> 14 <212> PRT <213> Homo sapiens <400> 846 Ala Gly Asp Phe Leu Glu Ala Asn Tyr Met Asn Leu Gln Arg 1 5 10 <210> 847 <211> 10 <212> PRT <213> Homo sapiens <400> 847 Cys Ala Glu Glu Asn Cys Phe Ile Gln Lys 1 5 10 <210> 848 <211> 10 <212> PRT <213> Homo sapiens <400> 848 Asp Phe Asp Phe Val Pro Pro Val Val Arg 1 5 10 <210> 849 <211> 20 <212> PRT <213> Homo sapiens <400> 849 Asp Thr Trp Val Glu His Trp Pro Glu Glu Asp Glu Cys Gln Asp Glu 1 5 10 15 Glu Asn Gln Lys 20 <210> 850 <211> 8 <212> PRT <213> Homo sapiens <400> 850 Glu Ala Leu Lys Leu Glu Glu Lys 1 5 <210> 851 <211> 25 <212> PRT <213> Homo sapiens <400> 851 Glu Gly Val Gln Lys Glu Asp Ile Pro Pro Ala Asp Leu Ser Asp Gln 1 5 10 15 Val Pro Asp Thr Glu Ser Glu Thr Arg 20 25 <210> 852 <211> 16 <212> PRT <213> Homo sapiens <400> 852 Glu Tyr Val Leu Pro Ser Phe Glu Val Ile Val Glu Pro Thr Glu Lys 1 5 10 15 <210> 853 <211> 9 <212> PRT <213> Homo sapiens <400> 853 Gly Tyr Thr Gln Gln Leu Ala Phe Arg 1 5 <210> 854 <211> 20 <212> PRT <213> Homo sapiens <400> 854 Gly Tyr Thr Gln Gln Leu Ala Phe Arg Gln Pro Ser Ser Ala Phe Ala 1 5 10 15 Ala Phe Val Lys 20 <210> 855 <211> 13 <212> PRT <213> Homo sapiens <400> 855 Ile Phe Thr Val Asn His Lys Leu Leu Pro Val Gly Arg 1 5 10 <210> 856 <211> 20 <212> PRT <213> Homo sapiens <400> 856 Ile Leu Leu Gln Gly Thr Pro Val Ala Gln Met Thr Glu Asp Ala Val 1 5 10 15 Asp Ala Glu Arg 20 <210> 857 <211> 10 <212> PRT <213> Homo sapiens <400> 857 Ile His Trp Glu Ser Ala Ser Leu Leu Arg 1 5 10 <210> 858 <211> 14 <212> PRT <213> Homo sapiens <400> 858 Ile Pro Ile Glu Asp Gly Ser Gly Glu Val Val Leu Ser Arg 1 5 10 <210> 859 <211> 11 <212> PRT <213> Homo sapiens <400> 859 Ile Arg Tyr Tyr Thr Tyr Leu Ile Met Asn Lys 1 5 10 <210> 860 <211> 12 <212> PRT <213> Homo sapiens <400> 860 Lys Gln Glu Leu Ser Glu Ala Glu Gln Ala Thr Arg 1 5 10 <210> 861 <211> 14 <212> PRT <213> Homo sapiens <400> 861 Lys Val Phe Leu Asp Cys Cys Asn Tyr Ile Thr Glu Leu Arg 1 5 10 <210> 862 <211> 15 <212> PRT <213> Homo sapiens <400> 862 Lys Val Phe Leu Asp Cys Cys Asn Tyr Ile Thr Glu Leu Arg Arg 1 5 10 15 <210> 863 <211> 11 <212> PRT <213> Homo sapiens <400> 863 Lys Val Leu Leu Asp Gly Val Gln Asn Pro Arg 1 5 10 <210> 864 <211> 14 <212> PRT <213> Homo sapiens <400> 864 Leu Asp Lys Ala Cys Glu Pro Gly Val Asp Tyr Val Tyr Lys 1 5 10 <210> 865 <211> 7 <212> PRT <213> Homo sapiens <400> 865 Leu Pro Tyr Ser Val Val Arg 1 5 <210> 866 <211> 17 <212> PRT <213> Homo sapiens <400> 866 Leu Ser Ile Asn Thr His Pro Ser Gln Lys Pro Leu Ser Ile Thr Val 1 5 10 15 Arg <210> 867 <211> 14 <212> PRT <213> Homo sapiens <400> 867 Leu Val Ala Tyr Tyr Thr Leu Ile Gly Ala Ser Gly Gln Arg 1 5 10 <210> 868 <211> 9 <212> PRT <213> Homo sapiens <400> 868 Asn Thr Leu Ile Ile Tyr Leu Asp Lys 1 5 <210> 869 <211> 11 <212> PRT <213> Homo sapiens <400> 869 Gln Glu Leu Ser Glu Ala Glu Gln Ala Thr Arg 1 5 10 <210> 870 <211> 15 <212> PRT <213> Homo sapiens <400> 870 Arg Ile Pro Ile Glu Asp Gly Ser Gly Glu Val Val Leu Ser Arg 1 5 10 15 <210> 871 <211> 10 <212> PRT <213> Homo sapiens <400> 871 Ser Asp Asp Lys Val Thr Leu Glu Glu Arg 1 5 10 <210> 872 <211> 13 <212> PRT <213> Homo sapiens <400> 872 Ser Asp Asp Lys Val Thr Leu Glu Glu Arg Leu Asp Lys 1 5 10 <210> 873 <211> 17 <212> PRT <213> Homo sapiens <400> 873 Ser Glu Glu Thr Lys Glu Asn Glu Gly Phe Thr Val Thr Ala Glu Gly 1 5 10 15 Lys <210> 874 <211> 16 <212> PRT <213> Homo sapiens <400> 874 Ser Gly Ile Pro Ile Val Thr Ser Pro Tyr Gln Ile His Phe Thr Lys 1 5 10 15 <210> 875 <211> 12 <212> PRT <213> Homo sapiens <400> 875 Ser Gly Ser Asp Glu Val Gln Val Gly Gln Gln Arg 1 5 10 <210> 876 <211> 16 <212> PRT <213> Homo sapiens <400> 876 Ser Asn Leu Asp Glu Asp Ile Ile Ala Glu Glu Asn Ile Val Ser Arg 1 5 10 15 <210> 877 <211> 13 <212> PRT <213> Homo sapiens <400> 877 Ser Ser Leu Ser Val Pro Tyr Val Ile Val Pro Leu Lys 1 5 10 <210> 878 <211> 22 <212> PRT <213> Homo sapiens <400> 878 Ser Ser Leu Ser Val Pro Tyr Val Ile Val Pro Leu Lys Thr Gly Leu 1 5 10 15 Gln Glu Val Glu Val Lys 20 <210> 879 <211> 8 <212> PRT <213> Homo sapiens <400> 879 Ser Val Gln Leu Thr Glu Lys Arg 1 5 <210> 880 <211> 16 <212> PRT <213> Homo sapiens <400> 880 Thr Glu Leu Arg Pro Gly Glu Thr Leu Asn Val Asn Phe Leu Leu Arg 1 5 10 15 <210> 881 <211> 9 <212> PRT <213> Homo sapiens <400> 881 Thr Gly Leu Gln Glu Val Glu Val Lys 1 5 <210> 882 <211> 14 <212> PRT <213> Homo sapiens <400> 882 Thr Lys Lys Gln Glu Leu Ser Glu Ala Glu Gln Ala Thr Arg 1 5 10 <210> 883 <211> 23 <212> PRT <213> Homo sapiens <400> 883 Thr Met Gln Ala Leu Pro Tyr Ser Thr Val Gly Asn Ser Asn Asn Tyr 1 5 10 15 Leu His Leu Ser Val Leu Arg 20 <210> 884 <211> 12 <212> PRT <213> Homo sapiens <400> 884 Thr Arg Phe Ile Ser Leu Gly Glu Ala Cys Lys Lys 1 5 10 <210> 885 <211> 16 <212> PRT <213> Homo sapiens <400> 885 Val Glu Leu Leu His Asn Pro Ala Phe Cys Ser Leu Ala Thr Thr Lys 1 5 10 15 <210> 886 <211> 13 <212> PRT <213> Homo sapiens <400> 886 Val Phe Leu Asp Cys Cys Asn Tyr Ile Thr Glu Leu Arg 1 5 10 <210> 887 <211> 14 <212> PRT <213> Homo sapiens <400> 887 Val Phe Leu Asp Cys Cys Asn Tyr Ile Thr Glu Leu Arg Arg 1 5 10 <210> 888 <211> 16 <212> PRT <213> Homo sapiens <400> 888 Val His Gln Tyr Phe Asn Val Glu Leu Ile Gln Pro Gly Ala Val Lys 1 5 10 15 <210> 889 <211> 10 <212> PRT <213> Homo sapiens <400> 889 Val Leu Leu Asp Gly Val Gln Asn Pro Arg 1 5 10 <210> 890 <211> 22 <212> PRT <213> Homo sapiens <400> 890 Val Pro Val Ala Val Gln Gly Glu Asp Thr Val Gln Ser Leu Thr Gln 1 5 10 15 Gly Asp Gly Val Ala Lys 20 <210> 891 <211> 12 <212> PRT <213> Homo sapiens <400> 891 Val Ser His Ser Glu Asp Asp Cys Leu Ala Phe Lys 1 5 10 <210> 892 <211> 11 <212> PRT <213> Homo sapiens <400> 892 Val Thr Ile Lys Pro Ala Pro Glu Thr Glu Lys 1 5 10 <210> 893 <211> 16 <212> PRT <213> Homo sapiens <400> 893 Val Val Leu Val Ala Val Asp Lys Gly Val Phe Val Leu Asn Lys Lys 1 5 10 15 <210> 894 <211> 13 <212> PRT <213> Homo sapiens <400> 894 Val Tyr Ala Tyr Tyr Asn Leu Glu Glu Ser Cys Thr Arg 1 5 10 <210> 895 <211> 9 <212> PRT <213> Homo sapiens <400> 895 Tyr Tyr Thr Tyr Leu Ile Met Asn Lys 1 5 <210> 896 <211> 17 <212> PRT <213> Homo sapiens <400> 896 Glu Ile Val His Leu Gln Ala Gly Gln Cys Gly Asn Gln Ile Gly Ala 1 5 10 15 Lys <210> 897 <211> 18 <212> PRT <213> Homo sapiens <400> 897 Gly His Tyr Thr Glu Gly Ala Glu Leu Val Asp Ser Val Leu Asp Val 1 5 10 15 Val Arg <210> 898 <211> 19 <212> PRT <213> Homo sapiens <400> 898 Gly His Tyr Thr Glu Gly Ala Glu Leu Val Asp Ser Val Leu Asp Val 1 5 10 15 Val Arg Lys <210> 899 <211> 16 <212> PRT <213> Homo sapiens <400> 899 Ile Asn Val Tyr Tyr Asn Glu Ala Thr Gly Gly Lys Tyr Val Pro Arg 1 5 10 15 <210> 900 <211> 14 <212> PRT <213> Homo sapiens <400> 900 Asn Ser Ser Tyr Phe Val Glu Trp Ile Pro Asn Asn Val Lys 1 5 10 <210> 901 <211> 26 <212> PRT <213> Homo sapiens <400> 901 Ser Gly Pro Phe Gly Gln Ile Phe Arg Pro Asp Asn Phe Val Phe Gly 1 5 10 15 Gln Ser Gly Ala Gly Asn Asn Trp Ala Lys 20 25 <210> 902 <211> 9 <212> PRT <213> Homo sapiens <400> 902 Tyr Leu Thr Val Ala Ala Val Phe Arg 1 5 <210> 903 <211> 16 <212> PRT <213> Homo sapiens <400> 903 Phe Ser Gly Ser Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg 1 5 10 15 <210> 904 <211> 8 <212> PRT <213> Homo sapiens <400> 904 Leu Thr Val Leu Ser Gln Pro Lys 1 5 <210> 905 <211> 18 <212> PRT <213> Homo sapiens <400> 905 Tyr Val Leu Thr Gln Pro Pro Ser Val Ser Val Ala Pro Gly Glu Thr 1 5 10 15 Ala Arg <210> 906 <211> 12 <212> PRT <213> Homo sapiens <400> 906 Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 1 5 10 <210> 907 <211> 9 <212> PRT <213> Homo sapiens <400> 907 Leu Leu Ile Tyr Gly Ala Ser Ser Arg 1 5 <210> 908 <211> 16 <212> PRT <213> Homo sapiens <400> 908 Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg 1 5 10 15 <210> 909 <211> 23 <212> PRT <213> Homo sapiens <400> 909 Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 1 5 10 15 Phe Thr Leu Thr Ile Ser Arg 20 <210> 910 <211> 22 <212> PRT <213> Homo sapiens <400> 910 Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 1 5 10 15 Pro Gly Gln Ala Pro Arg 20 <210> 911 <211> 11 <212> PRT <213> Homo sapiens <400> 911 Ala Ser Ser Leu Glu Ser Gly Val Pro Ser Arg 1 5 10 <210> 912 <211> 18 <212> PRT <213> Homo sapiens <400> 912 Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg <210> 913 <211> 24 <212> PRT <213> Homo sapiens <400> 913 Tyr Leu Thr Trp Ala Ser Arg Gln Glu Pro Ser Gln Gly Thr Thr Thr 1 5 10 15 Phe Ala Val Thr Ser Ile Leu Arg 20 <210> 914 <211> 7 <212> PRT <213> Homo sapiens <400> 914 Tyr Leu Thr Trp Ala Ser Arg 1 5 <210> 915 <211> 19 <212> PRT <213> Homo sapiens <400> 915 Trp Leu Gln Gly Ser Gln Glu Leu Pro Arg Glu Lys Tyr Leu Thr Trp 1 5 10 15 Ala Ser Arg <210> 916 <211> 12 <212> PRT <213> Homo sapiens <400> 916 Trp Leu Gln Gly Ser Gln Glu Leu Pro Arg Glu Lys 1 5 10 <210> 917 <211> 8 <212> PRT <213> Homo sapiens <400> 917 Val Ala Ala Glu Asp Trp Lys Lys 1 5 <210> 918 <211> 7 <212> PRT <213> Homo sapiens <400> 918 Val Ala Ala Glu Asp Trp Lys 1 5 <210> 919 <211> 9 <212> PRT <213> Homo sapiens <400> 919 Thr Pro Leu Thr Ala Thr Leu Ser Lys 1 5 <210> 920 <211> 21 <212> PRT <213> Homo sapiens <400> 920 Thr Phe Thr Cys Thr Ala Ala Tyr Pro Glu Ser Lys Thr Pro Leu Thr 1 5 10 15 Ala Thr Leu Ser Lys 20 <210> 921 <211> 12 <212> PRT <213> Homo sapiens <400> 921 Thr Phe Thr Cys Thr Ala Ala Tyr Pro Glu Ser Lys 1 5 10 <210> 922 <211> 7 <212> PRT <213> Homo sapiens <400> 922 Ser Val Thr Cys His Val Lys 1 5 <210> 923 <211> 32 <212> PRT <213> Homo sapiens <400> 923 Ser Gly Asn Thr Phe Arg Pro Glu Val His Leu Leu Pro Pro Pro Ser 1 5 10 15 Glu Glu Leu Ala Leu Asn Glu Leu Val Thr Leu Thr Cys Leu Ala Arg 20 25 30 <210> 924 <211> 32 <212> PRT <213> Homo sapiens <400> 924 Ser Ala Val Gln Gly Pro Pro Glu Arg Asp Leu Cys Gly Cys Tyr Ser 1 5 10 15 Val Ser Ser Val Leu Pro Gly Cys Ala Glu Pro Trp Asn His Gly Lys 20 25 30 <210> 925 <211> 9 <212> PRT <213> Homo sapiens <400> 925 Ser Ala Val Gln Gly Pro Pro Glu Arg 1 5 <210> 926 <211> 17 <212> PRT <213> Homo sapiens <400> 926 Gln Glu Pro Ser Gln Gly Thr Thr Thr Phe Ala Val Thr Ser Ile Leu 1 5 10 15 Arg <210> 927 <211> 30 <212> PRT <213> Homo sapiens <400> 927 Asn Phe Pro Pro Ser Gln Asp Ala Ser Gly Asp Leu Tyr Thr Thr Ser 1 5 10 15 Ser Gln Leu Thr Leu Pro Ala Thr Gln Cys Leu Ala Gly Lys 20 25 30 <210> 928 <211> 21 <212> PRT <213> Homo sapiens <400> 928 Lys Gly Asp Thr Phe Ser Cys Met Val Gly His Glu Ala Leu Pro Leu 1 5 10 15 Ala Phe Thr Gln Lys 20 <210> 929 <211> 20 <212> PRT <213> Homo sapiens <400> 929 Gly Phe Ser Pro Lys Asp Val Leu Val Arg Trp Leu Gln Gly Ser Gln 1 5 10 15 Glu Leu Pro Arg 20 <210> 930 <211> 10 <212> PRT <213> Homo sapiens <400> 930 Gly Phe Ser Pro Lys Asp Val Leu Val Arg 1 5 10 <210> 931 <211> 20 <212> PRT <213> Homo sapiens <400> 931 Gly Asp Thr Phe Ser Cys Met Val Gly His Glu Ala Leu Pro Leu Ala 1 5 10 15 Phe Thr Gln Lys 20 <210> 932 <211> 26 <212> PRT <213> Homo sapiens <400> 932 Glu Lys Tyr Leu Thr Trp Ala Ser Arg Gln Glu Pro Ser Gln Gly Thr 1 5 10 15 Thr Thr Phe Ala Val Thr Ser Ile Leu Arg 20 25 <210> 933 <211> 9 <212> PRT <213> Homo sapiens <400> 933 Glu Lys Tyr Leu Thr Trp Ala Ser Arg 1 5 <210> 934 <211> 17 <212> PRT <213> Homo sapiens <400> 934 Asp Val Leu Val Arg Trp Leu Gln Gly Ser Gln Glu Leu Pro Arg Glu 1 5 10 15 Lys <210> 935 <211> 15 <212> PRT <213> Homo sapiens <400> 935 Asp Val Leu Val Arg Trp Leu Gln Gly Ser Gln Glu Leu Pro Arg 1 5 10 15 <210> 936 <211> 23 <212> PRT <213> Homo sapiens <400> 936 Asp Leu Cys Gly Cys Tyr Ser Val Ser Ser Val Leu Pro Gly Cys Ala 1 5 10 15 Glu Pro Trp Asn His Gly Lys 20 <210> 937 <211> 15 <212> PRT <213> Homo sapiens <400> 937 Asp Ala Ser Gly Val Thr Phe Thr Trp Thr Pro Ser Ser Gly Lys 1 5 10 15 <210> 938 <211> 12 <212> PRT <213> Homo sapiens <400> 938 Ala Glu Thr Gly Asp Lys Val Tyr Val His Leu Lys 1 5 10 <210> 939 <211> 12 <212> PRT <213> Homo sapiens <400> 939 Ala Leu Tyr Leu Gln Tyr Thr Asp Glu Thr Phe Arg 1 5 10 <210> 940 <211> 14 <212> PRT <213> Homo sapiens <400> 940 Asp Ile Ala Ser Gly Leu Ile Gly Pro Leu Ile Ile Cys Lys 1 5 10 <210> 941 <211> 14 <212> PRT <213> Homo sapiens <400> 941 Asp Leu Tyr Ser Gly Leu Ile Gly Pro Leu Ile Val Cys Arg 1 5 10 <210> 942 <211> 14 <212> PRT <213> Homo sapiens <400> 942 Glu Val Gly Pro Thr Asn Ala Asp Pro Val Cys Leu Ala Lys 1 5 10 <210> 943 <211> 10 <212> PRT <213> Homo sapiens <400> 943 Glu Tyr Thr Asp Ala Ser Phe Thr Asn Arg 1 5 10 <210> 944 <211> 19 <212> PRT <213> Homo sapiens <400> 944 Phe Asn Lys Asn Asn Glu Gly Thr Tyr Tyr Ser Pro Asn Tyr Asn Pro 1 5 10 15 Gln Ser Arg <210> 945 <211> 13 <212> PRT <213> Homo sapiens <400> 945 Gly Ala Tyr Pro Leu Ser Ile Glu Pro Ile Gly Val Arg 1 5 10 <210> 946 <211> 20 <212> PRT <213> Homo sapiens <400> 946 His Tyr Tyr Ile Gly Ile Ile Glu Thr Thr Trp Asp Tyr Ala Ser Asp 1 5 10 15 His Gly Glu Lys 20 <210> 947 <211> 23 <212> PRT <213> Homo sapiens <400> 947 Lys Ala Glu Glu Glu His Leu Gly Ile Leu Gly Pro Gln Leu His Ala 1 5 10 15 Asp Val Gly Asp Lys Val Lys 20 <210> 948 <211> 13 <212> PRT <213> Homo sapiens <400> 948 Lys Ala Leu Tyr Leu Gln Tyr Thr Asp Glu Thr Phe Arg 1 5 10 <210> 949 <211> 20 <212> PRT <213> Homo sapiens <400> 949 Lys Leu Ile Ser Val Asp Thr Glu His Ser Asn Ile Tyr Leu Gln Asn 1 5 10 15 Gly Pro Asp Arg 20 <210> 950 <211> 19 <212> PRT <213> Homo sapiens <400> 950 Leu Ile Ser Val Asp Thr Glu His Ser Asn Ile Tyr Leu Gln Asn Gly 1 5 10 15 Pro Asp Arg <210> 951 <211> 16 <212> PRT <213> Homo sapiens <400> 951 Asn Asn Glu Gly Thr Tyr Tyr Ser Pro Asn Tyr Asn Pro Gln Ser Arg 1 5 10 15 <210> 952 <211> 12 <212> PRT <213> Homo sapiens <400> 952 Gln Ser Glu Asp Ser Thr Phe Tyr Leu Gly Glu Arg 1 5 10 <210> 953 <211> 23 <212> PRT <213> Homo sapiens <400> 953 Ser Gly Ala Gly Thr Glu Asp Ser Ala Cys Ile Pro Trp Ala Tyr Tyr 1 5 10 15 Ser Thr Val Asp Gln Val Lys 20 <210> 954 <211> 23 <212> PRT <213> Homo sapiens <400> 954 Ser Val Pro Pro Ser Ala Ser His Val Ala Pro Thr Glu Thr Phe Thr 1 5 10 15 Tyr Glu Trp Thr Val Pro Lys 20 <210> 955 <211> 21 <212> PRT <213> Homo sapiens <400> 955 Thr Tyr Cys Ser Glu Pro Glu Lys Val Asp Lys Asp Asn Glu Asp Phe 1 5 10 15 Gln Glu Ser Asn Arg 20 <210> 956 <211> 13 <212> PRT <213> Homo sapiens <400> 956 Val Asn Lys Asp Asp Glu Glu Phe Ile Glu Ser Asn Lys 1 5 10 <210> 957 <211> 7 <212> PRT <213> Homo sapiens <400> 957 Tyr Thr Val Asn Gln Cys Arg 1 5 <210> 958 <211> 15 <212> PRT <213> Homo sapiens <400> 958 Ala Asp Arg Asp Gln Tyr Glu Leu Leu Cys Leu Asp Asn Thr Arg 1 5 10 15 <210> 959 <211> 9 <212> PRT <213> Homo sapiens <400> 959 Ala Pro Asn His Ala Val Val Thr Arg 1 5 <210> 960 <211> 8 <212> PRT <213> Homo sapiens <400> 960 Ala Ser Tyr Leu Asp Cys Ile Arg 1 5 <210> 961 <211> 11 <212> PRT <213> Homo sapiens <400> 961 Cys Asp Glu Trp Ser Val Asn Ser Val Gly Lys 1 5 10 <210> 962 <211> 13 <212> PRT <213> Homo sapiens <400> 962 Cys Leu Lys Asp Gly Ala Gly Asp Val Ala Phe Val Lys 1 5 10 <210> 963 <211> 12 <212> PRT <213> Homo sapiens <400> 963 Cys Leu Val Glu Lys Gly Asp Val Ala Phe Val Lys 1 5 10 <210> 964 <211> 13 <212> PRT <213> Homo sapiens <400> 964 Cys Ser Thr Ser Ser Leu Leu Glu Ala Cys Thr Phe Arg 1 5 10 <210> 965 <211> 15 <212> PRT <213> Homo sapiens <400> 965 Cys Ser Thr Ser Ser Leu Leu Glu Ala Cys Thr Phe Arg Arg Pro 1 5 10 15 <210> 966 <211> 15 <212> PRT <213> Homo sapiens <400> 966 Asp Cys His Leu Ala Gln Val Pro Ser His Thr Val Val Ala Arg 1 5 10 15 <210> 967 <211> 8 <212> PRT <213> Homo sapiens <400> 967 Asp Asp Thr Val Cys Leu Ala Lys 1 5 <210> 968 <211> 10 <212> PRT <213> Homo sapiens <400> 968 Asp Gly Ala Gly Asp Val Ala Phe Val Lys 1 5 10 <210> 969 <211> 8 <212> PRT <213> Homo sapiens <400> 969 Asp Lys Glu Ala Cys Val His Lys 1 5 <210> 970 <211> 11 <212> PRT <213> Homo sapiens <400> 970 Asp Lys Glu Ala Cys Val His Lys Ile Leu Arg 1 5 10 <210> 971 <211> 13 <212> PRT <213> Homo sapiens <400> 971 Asp Leu Leu Phe Lys Asp Ser Ala His Gly Phe Leu Lys 1 5 10 <210> 972 <211> 17 <212> PRT <213> Homo sapiens <400> 972 Asp Leu Leu Phe Lys Asp Ser Ala His Gly Phe Leu Lys Val Pro Pro 1 5 10 15 Arg <210> 973 <211> 13 <212> PRT <213> Homo sapiens <400> 973 Asp Leu Leu Phe Arg Asp Asp Thr Val Cys Leu Ala Lys 1 5 10 <210> 974 <211> 12 <212> PRT <213> Homo sapiens <400> 974 Asp Ser Ala His Gly Phe Leu Lys Val Pro Pro Arg 1 5 10 <210> 975 <211> 10 <212> PRT <213> Homo sapiens <400> 975 Asp Ser Gly Phe Gln Met Asn Gln Leu Arg 1 5 10 <210> 976 <211> 11 <212> PRT <213> Homo sapiens <400> 976 Asp Tyr Glu Leu Leu Cys Leu Asp Gly Thr Arg 1 5 10 <210> 977 <211> 12 <212> PRT <213> Homo sapiens <400> 977 Asp Tyr Glu Leu Leu Cys Leu Asp Gly Thr Arg Lys 1 5 10 <210> 978 <211> 24 <212> PRT <213> Homo sapiens <400> 978 Asp Tyr Glu Leu Leu Cys Leu Asp Gly Thr Arg Lys Pro Val Glu Glu 1 5 10 15 Tyr Ala Asn Cys His Leu Ala Arg 20 <210> 979 <211> 14 <212> PRT <213> Homo sapiens <400> 979 Glu Asp Pro Gln Thr Phe Tyr Tyr Ala Val Ala Val Val Lys 1 5 10 <210> 980 <211> 15 <212> PRT <213> Homo sapiens <400> 980 Glu Asp Pro Gln Thr Phe Tyr Tyr Ala Val Ala Val Val Lys Lys 1 5 10 15 <210> 981 <211> 11 <212> PRT <213> Homo sapiens <400> 981 Glu Phe Gln Leu Phe Ser Ser Pro His Gly Lys 1 5 10 <210> 982 <211> 16 <212> PRT <213> Homo sapiens <400> 982 Glu Phe Gln Leu Phe Ser Ser Pro His Gly Lys Asp Leu Leu Phe Lys 1 5 10 15 <210> 983 <211> 11 <212> PRT <213> Homo sapiens <400> 983 Glu Gly Tyr Tyr Gly Tyr Thr Gly Ala Phe Arg 1 5 10 <210> 984 <211> 16 <212> PRT <213> Homo sapiens <400> 984 Glu Gly Thr Cys Pro Glu Ala Pro Thr Asp Glu Cys Lys Pro Val Lys 1 5 10 15 <210> 985 <211> 14 <212> PRT <213> Homo sapiens <400> 985 Phe Asp Glu Phe Phe Ser Glu Gly Cys Ala Pro Gly Ser Lys 1 5 10 <210> 986 <211> 15 <212> PRT <213> Homo sapiens <400> 986 Phe Asp Glu Phe Phe Ser Glu Gly Cys Ala Pro Gly Ser Lys Lys 1 5 10 15 <210> 987 <211> 18 <212> PRT <213> Homo sapiens <400> 987 Gly Asp Val Ala Phe Val Lys His Gln Thr Val Pro Gln Asn Thr Gly 1 5 10 15 Gly Lys <210> 988 <211> 21 <212> PRT <213> Homo sapiens <400> 988 Phe Asp Glu Phe Phe Ser Glu Gly Cys Ala Pro Gly Ser Lys Lys Asp 1 5 10 15 Ser Ser Leu Cys Lys 20 <210> 989 <211> 11 <212> PRT <213> Homo sapiens <400> 989 His Gln Thr Val Pro Gln Asn Thr Gly Gly Lys 1 5 10 <210> 990 <211> 18 <212> PRT <213> Homo sapiens <400> 990 His Gln Thr Val Pro Gln Asn Thr Gly Gly Lys Asn Pro Asp Pro Trp 1 5 10 15 Ala Lys <210> 991 <211> 23 <212> PRT <213> Homo sapiens <400> 991 His Gln Thr Val Pro Gln Asn Thr Gly Gly Lys Asn Pro Asp Pro Trp 1 5 10 15 Ala Lys Asn Leu Asn Glu Lys 20 <210> 992 <211> 11 <212> PRT <213> Homo sapiens <400> 992 His Ser Thr Ile Phe Glu Asn Leu Ala Asn Lys 1 5 10 <210> 993 <211> 14 <212> PRT <213> Homo sapiens <400> 993 His Ser Thr Ile Phe Glu Asn Leu Ala Asn Lys Ala Asp Arg 1 5 10 <210> 994 <211> 15 <212> PRT <213> Homo sapiens <400> 994 Ile Glu Cys Val Ser Ala Glu Thr Thr Glu Asp Cys Ile Ala Lys 1 5 10 15 <210> 995 <211> 19 <212> PRT <213> Homo sapiens <400> 995 Ile Asn His Cys Arg Phe Asp Glu Phe Phe Ser Glu Gly Cys Ala Pro 1 5 10 15 Gly Ser Lys <210> 996 <211> 20 <212> PRT <213> Homo sapiens <400> 996 Ile Asn His Cys Arg Phe Asp Glu Phe Phe Ser Glu Gly Cys Ala Pro 1 5 10 15 Gly Ser Lys Lys 20 <210> 997 <211> 14 <212> PRT <213> Homo sapiens <400> 997 Lys Cys Ser Thr Ser Ser Leu Leu Glu Ala Cys Thr Phe Arg 1 5 10 <210> 998 <211> 11 <212> PRT <213> Homo sapiens <400> 998 Lys Asp Ser Gly Phe Gln Met Asn Gln Leu Arg 1 5 10 <210> 999 <211> 13 <212> PRT <213> Homo sapiens <400> 999 Lys Pro Val Glu Glu Tyr Ala Asn Cys His Leu Ala Arg 1 5 10 <210> 1000 <211> 12 <212> PRT <213> Homo sapiens <400> 1000 Lys Ser Ala Ser Asp Leu Thr Trp Asp Asn Leu Lys 1 5 10 <210> 1001 <211> 15 <212> PRT <213> Homo sapiens <400> 1001 Leu Cys Met Gly Ser Gly Leu Asn Leu Cys Glu Pro Asn Asn Lys 1 5 10 15 <210> 1002 <211> 26 <212> PRT <213> Homo sapiens <400> 1002 Leu Cys Met Gly Ser Gly Leu Asn Leu Cys Glu Pro Asn Asn Lys Glu 1 5 10 15 Gly Tyr Tyr Gly Tyr Thr Gly Ala Phe Arg 20 25 <210> 1003 <211> 17 <212> PRT <213> Homo sapiens <400> 1003 Leu His Asp Arg Asn Thr Tyr Glu Lys Tyr Leu Gly Glu Glu Tyr Val 1 5 10 15 Lys <210> 1004 <211> 13 <212> PRT <213> Homo sapiens <400> 1004 Leu Lys Cys Asp Glu Trp Ser Val Asn Ser Val Gly Lys 1 5 10 <210> 1005 <211> 28 <212> PRT <213> Homo sapiens <400> 1005 Leu Lys Cys Asp Glu Trp Ser Val Asn Ser Val Gly Lys Ile Glu Cys 1 5 10 15 Val Ser Ala Glu Thr Thr Glu Asp Cys Ile Ala Lys 20 25 <210> 1006 <211> 12 <212> PRT <213> Homo sapiens <400> 1006 Met Tyr Leu Gly Tyr Glu Tyr Val Thr Ala Ile Arg 1 5 10 <210> 1007 <211> 15 <212> PRT <213> Homo sapiens <400> 1007 Met Tyr Leu Gly Tyr Glu Tyr Val Thr Ala Ile Arg Asn Leu Arg 1 5 10 15 <210> 1008 <211> 16 <212> PRT <213> Homo sapiens <400> 1008 Asn Leu Asn Glu Lys Asp Tyr Glu Leu Leu Cys Leu Asp Gly Thr Arg 1 5 10 15 <210> 1009 <211> 17 <212> PRT <213> Homo sapiens <400> 1009 Asn Leu Asn Glu Lys Asp Tyr Glu Leu Leu Cys Leu Asp Gly Thr Arg 1 5 10 15 Lys <210> 1010 <211> 19 <212> PRT <213> Homo sapiens <400> 1010 Asn Leu Arg Glu Gly Thr Cys Pro Glu Ala Pro Thr Asp Glu Cys Lys 1 5 10 15 Pro Val Lys <210> 1011 <211> 7 <212> PRT <213> Homo sapiens <400> 1011 Asn Pro Asp Pro Trp Ala Lys 1 5 <210> 1012 <211> 19 <212> PRT <213> Homo sapiens <400> 1012 Ser Ala Gly Trp Asn Ile Pro Ile Gly Leu Leu Tyr Cys Asp Leu Pro 1 5 10 15 Glu Pro Arg <210> 1013 <211> 24 <212> PRT <213> Homo sapiens <400> 1013 Ser Ala Gly Trp Asn Ile Pro Ile Gly Leu Leu Tyr Cys Asp Leu Pro 1 5 10 15 Glu Pro Arg Lys Pro Leu Glu Lys 20 <210> 1014 <211> 11 <212> PRT <213> Homo sapiens <400> 1014 Ser Ala Ser Asp Leu Thr Trp Asp Asn Leu Lys 1 5 10 <210> 1015 <211> 13 <212> PRT <213> Homo sapiens <400> 1015 Ser Ala Ser Asp Leu Thr Trp Asp Asn Leu Lys Gly Lys 1 5 10 <210> 1016 <211> 14 <212> PRT <213> Homo sapiens <400> 1016 Ser Ala Ser Asp Leu Thr Trp Asp Asn Leu Lys Gly Lys Lys 1 5 10 <210> 1017 <211> 17 <212> PRT <213> Homo sapiens <400> 1017 Ser Glu Thr Lys Asp Leu Leu Phe Arg Asp Asp Thr Val Cys Leu Ala 1 5 10 15 Lys <210> 1018 <211> 13 <212> PRT <213> Homo sapiens <400> 1018 Ser Lys Glu Phe Gln Leu Phe Ser Ser Pro His Gly Lys 1 5 10 <210> 1019 <211> 18 <212> PRT <213> Homo sapiens <400> 1019 Ser Lys Glu Phe Gln Leu Phe Ser Ser Pro His Gly Lys Asp Leu Leu 1 5 10 15 Phe Lys <210> 1020 <211> 22 <212> PRT <213> Homo sapiens <400> 1020 Ser Met Gly Gly Lys Glu Asp Leu Ile Trp Glu Leu Leu Asn Gln Ala 1 5 10 15 Gln Glu His Phe Gly Lys 20 <210> 1021 <211> 14 <212> PRT <213> Homo sapiens <400> 1021 Ser Val Ile Pro Ser Asp Gly Pro Ser Val Ala Cys Val Lys 1 5 10 <210> 1022 <211> 11 <212> PRT <213> Homo sapiens <400> 1022 Trp Cys Ala Val Ser Glu His Glu Ala Thr Lys 1 5 10 <210> 1023 <211> 14 <212> PRT <213> Homo sapiens <400> 1023 Thr Ala Gly Trp Asn Ile Pro Met Gly Leu Leu Tyr Asn Lys 1 5 10 <210> 1024 <211> 8 <212> PRT <213> Homo sapiens <400> 1024 Tyr Leu Gly Glu Glu Tyr Val Lys 1 5 <210> 1025 <211> 15 <212> PRT <213> Homo sapiens <400> 1025 Tyr Leu Gly Glu Glu Tyr Val Lys Ala Val Gly Asn Leu Arg Lys 1 5 10 15 <210> 1026 <211> 339 <212> PRT <213> Homo sapiens <400> 1026 Met Trp Gln Leu Trp Ala Ser Leu Cys Cys Leu Leu Val Leu Ala Asn 1 5 10 15 Ala Arg Ser Arg Pro Ser Phe His Pro Leu Ser Asp Glu Leu Val Asn 20 25 30 Tyr Val Asn Lys Arg Asn Thr Thr Trp Gln Ala Gly His Asn Phe Tyr 35 40 45 Asn Val Asp Met Ser Tyr Leu Lys Arg Leu Cys Gly Thr Phe Leu Gly 50 55 60 Gly Pro Lys Pro Pro Gln Arg Val Met Phe Thr Glu Asp Leu Lys Leu 65 70 75 80 Pro Ala Ser Phe Asp Ala Arg Glu Gln Trp Pro Gln Cys Pro Thr Ile 85 90 95 Lys Glu Ile Arg Asp Gln Gly Ser Cys Gly Ser Cys Trp Ala Phe Gly 100 105 110 Ala Val Glu Ala Ile Ser Asp Arg Ile Cys Ile His Thr Asn Ala His 115 120 125 Val Ser Val Glu Val Ser Ala Glu Asp Leu Leu Thr Cys Cys Gly Ser 130 135 140 Met Cys Gly Asp Gly Cys Asn Gly Gly Tyr Pro Ala Glu Ala Trp Asn 145 150 155 160 Phe Trp Thr Arg Lys Gly Leu Val Ser Gly Gly Leu Tyr Glu Ser His 165 170 175 Val Gly Cys Arg Pro Tyr Ser Ile Pro Pro Cys Glu His His Val Asn 180 185 190 Gly Ser Arg Pro Pro Cys Thr Gly Glu Gly Asp Thr Pro Lys Cys Ser 195 200 205 Lys Ile Cys Glu Pro Gly Tyr Ser Pro Thr Tyr Lys Gln Asp Lys His 210 215 220 Tyr Gly Tyr Asn Ser Tyr Ser Val Ser Asn Ser Glu Lys Asp Ile Met 225 230 235 240 Ala Glu Ile Tyr Lys Asn Gly Pro Val Glu Gly Ala Phe Ser Val Tyr 245 250 255 Ser Asp Phe Leu Leu Tyr Lys Ser Gly Val Tyr Gln His Val Thr Gly 260 265 270 Glu Met Met Gly Gly His Ala Ile Arg Ile Leu Gly Trp Gly Val Glu 275 280 285 Asn Gly Thr Pro Tyr Trp Leu Val Ala Asn Ser Trp Asn Thr Asp Trp 290 295 300 Gly Asp Asn Gly Phe Phe Lys Ile Leu Arg Gly Gln Asp His Cys Gly 305 310 315 320 Ile Glu Ser Glu Val Val Ala Gly Ile Pro Arg Thr Asp Gln Tyr Trp 325 330 335 Glu Lys Ile <210> 1027 <211> 1065 <212> PRT <213> Homo sapiens <400> 1027 Met Lys Ile Leu Ile Leu Gly Ile Phe Leu Phe Leu Cys Ser Thr Pro 1 5 10 15 Ala Trp Ala Lys Glu Lys His Tyr Tyr Ile Gly Ile Ile Glu Thr Thr 20 25 30 Trp Asp Tyr Ala Ser Asp His Gly Glu Lys Lys Leu Ile Ser Val Asp 35 40 45 Thr Glu His Ser Asn Ile Tyr Leu Gln Asn Gly Pro Asp Arg Ile Gly 50 55 60 Arg Leu Tyr Lys Lys Ala Leu Tyr Leu Gln Tyr Thr Asp Glu Thr Phe 65 70 75 80 Arg Thr Thr Ile Glu Lys Pro Val Trp Leu Gly Phe Leu Gly Pro Ile 85 90 95 Ile Lys Ala Glu Thr Gly Asp Lys Val Tyr Val His Leu Lys Asn Leu 100 105 110 Ala Ser Arg Pro Tyr Thr Phe His Ser His Gly Ile Thr Tyr Tyr Lys 115 120 125 Glu His Glu Gly Ala Ile Tyr Pro Asp Asn Thr Thr Asp Phe Gln Arg 130 135 140 Ala Asp Asp Lys Val Tyr Pro Gly Glu Gln Tyr Thr Tyr Met Leu Leu 145 150 155 160 Ala Thr Glu Glu Gln Ser Pro Gly Glu Gly Asp Gly Asn Cys Val Thr 165 170 175 Arg Ile Tyr His Ser His Ile Asp Ala Pro Lys Asp Ile Ala Ser Gly 180 185 190 Leu Ile Gly Pro Leu Ile Ile Cys Lys Lys Asp Ser Leu Asp Lys Glu 195 200 205 Lys Glu Lys His Ile Asp Arg Glu Phe Val Val Met Phe Ser Val Val 210 215 220 Asp Glu Asn Phe Ser Trp Tyr Leu Glu Asp Asn Ile Lys Thr Tyr Cys 225 230 235 240 Ser Glu Pro Glu Lys Val Asp Lys Asp Asn Glu Asp Phe Gln Glu Ser 245 250 255 Asn Arg Met Tyr Ser Val Asn Gly Tyr Thr Phe Gly Ser Leu Pro Gly 260 265 270 Leu Ser Met Cys Ala Glu Asp Arg Val Lys Trp Tyr Leu Phe Gly Met 275 280 285 Gly Asn Glu Val Asp Val His Ala Ala Phe Phe His Gly Gln Ala Leu 290 295 300 Thr Asn Lys Asn Tyr Arg Ile Asp Thr Ile Asn Leu Phe Pro Ala Thr 305 310 315 320 Leu Phe Asp Ala Tyr Met Val Ala Gln Asn Pro Gly Glu Trp Met Leu 325 330 335 Ser Cys Gln Asn Leu Asn His Leu Lys Ala Gly Leu Gln Ala Phe Phe 340 345 350 Gln Val Gln Glu Cys Asn Lys Ser Ser Ser Lys Asp Asn Ile Arg Gly 355 360 365 Lys His Val Arg His Tyr Tyr Ile Ala Ala Glu Glu Ile Ile Trp Asn 370 375 380 Tyr Ala Pro Ser Gly Ile Asp Ile Phe Thr Lys Glu Asn Leu Thr Ala 385 390 395 400 Pro Gly Ser Asp Ser Ala Val Phe Phe Glu Gln Gly Thr Thr Arg Ile 405 410 415 Gly Gly Ser Tyr Lys Lys Leu Val Tyr Arg Glu Tyr Thr Asp Ala Ser 420 425 430 Phe Thr Asn Arg Lys Glu Arg Gly Pro Glu Glu Glu His Leu Gly Ile 435 440 445 Leu Gly Pro Val Ile Trp Ala Glu Val Gly Asp Thr Ile Arg Val Thr 450 455 460 Phe His Asn Lys Gly Ala Tyr Pro Leu Ser Ile Glu Pro Ile Gly Val 465 470 475 480 Arg Phe Asn Lys Asn Asn Glu Gly Thr Tyr Tyr Ser Pro Asn Tyr Asn 485 490 495 Pro Gln Ser Arg Ser Val Pro Pro Ser Ala Ser His Val Ala Pro Thr 500 505 510 Glu Thr Phe Thr Tyr Glu Trp Thr Val Pro Lys Glu Val Gly Pro Thr 515 520 525 Asn Ala Asp Pro Val Cys Leu Ala Lys Met Tyr Tyr Ser Ala Val Asp 530 535 540 Pro Thr Lys Asp Ile Phe Thr Gly Leu Ile Gly Pro Met Lys Ile Cys 545 550 555 560 Lys Lys Gly Ser Leu His Ala Asn Gly Arg Gln Lys Asp Val Asp Lys 565 570 575 Glu Phe Tyr Leu Phe Pro Thr Val Phe Asp Glu Asn Glu Ser Leu Leu 580 585 590 Leu Glu Asp Asn Ile Arg Met Phe Thr Thr Ala Pro Asp Gln Val Asp 595 600 605 Lys Glu Asp Glu Asp Phe Gln Glu Ser Asn Lys Met His Ser Met Asn 610 615 620 Gly Phe Met Tyr Gly Asn Gln Pro Gly Leu Thr Met Cys Lys Gly Asp 625 630 635 640 Ser Val Val Trp Tyr Leu Phe Ser Ala Gly Asn Glu Ala Asp Val His 645 650 655 Gly Ile Tyr Phe Ser Gly Asn Thr Tyr Leu Trp Arg Gly Glu Arg Arg 660 665 670 Asp Thr Ala Asn Leu Phe Pro Gln Thr Ser Leu Thr Leu His Met Trp 675 680 685 Pro Asp Thr Glu Gly Thr Phe Asn Val Glu Cys Leu Thr Thr Asp His 690 695 700 Tyr Thr Gly Gly Met Lys Gln Lys Tyr Thr Val Asn Gln Cys Arg Arg 705 710 715 720 Gln Ser Glu Asp Ser Thr Phe Tyr Leu Gly Glu Arg Thr Tyr Tyr Ile 725 730 735 Ala Ala Val Glu Val Glu Trp Asp Tyr Ser Pro Gln Arg Glu Trp Glu 740 745 750 Lys Glu Leu His His Leu Gln Glu Gln Asn Val Ser Asn Ala Phe Leu 755 760 765 Asp Lys Gly Glu Phe Tyr Ile Gly Ser Lys Tyr Lys Lys Val Val Tyr 770 775 780 Arg Gln Tyr Thr Asp Ser Thr Phe Arg Val Pro Val Glu Arg Lys Ala 785 790 795 800 Glu Glu Glu His Leu Gly Ile Leu Gly Pro Gln Leu His Ala Asp Val 805 810 815 Gly Asp Lys Val Lys Ile Ile Phe Lys Asn Met Ala Thr Arg Pro Tyr 820 825 830 Ser Ile His Ala His Gly Val Gln Thr Glu Ser Ser Thr Val Thr Pro 835 840 845 Thr Leu Pro Gly Glu Thr Leu Thr Tyr Val Trp Lys Ile Pro Glu Arg 850 855 860 Ser Gly Ala Gly Thr Glu Asp Ser Ala Cys Ile Pro Trp Ala Tyr Tyr 865 870 875 880 Ser Thr Val Asp Gln Val Lys Asp Leu Tyr Ser Gly Leu Ile Gly Pro 885 890 895 Leu Ile Val Cys Arg Arg Pro Tyr Leu Lys Val Phe Asn Pro Arg Arg 900 905 910 Lys Leu Glu Phe Ala Leu Leu Phe Leu Val Phe Asp Glu Asn Glu Ser 915 920 925 Trp Tyr Leu Asp Asp Asn Ile Lys Thr Tyr Ser Asp His Pro Glu Lys 930 935 940 Val Asn Lys Asp Asp Glu Glu Phe Ile Glu Ser Asn Lys Met His Ala 945 950 955 960 Ile Asn Gly Arg Met Phe Gly Asn Leu Gln Gly Leu Thr Met His Val 965 970 975 Gly Asp Glu Val Asn Trp Tyr Leu Met Gly Met Gly Asn Glu Ile Asp 980 985 990 Leu His Thr Val His Phe His Gly His Ser Phe Gln Tyr Lys His Arg 995 1000 1005 Gly Val Tyr Ser Ser Asp Val Phe Asp Ile Phe Pro Gly Thr Tyr 1010 1015 1020 Gln Thr Leu Glu Met Phe Pro Arg Thr Pro Gly Ile Trp Leu Leu 1025 1030 1035 His Cys His Val Thr Asp His Ile His Ala Gly Met Glu Thr Thr 1040 1045 1050 Tyr Thr Val Leu Gln Asn Glu Asp Thr Lys Ser Gly 1055 1060 1065 <210> 1028 <211> 248 <212> PRT <213> Homo sapiens <400> 1028 Met Glu Arg Ala Ser Leu Ile Gln Lys Ala Lys Leu Ala Glu Gln Ala 1 5 10 15 Glu Arg Tyr Glu Asp Met Ala Ala Phe Met Lys Gly Ala Val Glu Lys 20 25 30 Gly Glu Glu Leu Ser Cys Glu Glu Arg Asn Leu Leu Ser Val Ala Tyr 35 40 45 Lys Asn Val Val Gly Gly Gln Arg Ala Ala Trp Arg Val Leu Ser Ser 50 55 60 Ile Glu Gln Lys Ser Asn Glu Glu Gly Ser Glu Glu Lys Gly Pro Glu 65 70 75 80 Val Arg Glu Tyr Arg Glu Lys Val Glu Thr Glu Leu Gln Gly Val Cys 85 90 95 Asp Thr Val Leu Gly Leu Leu Asp Ser His Leu Ile Lys Glu Ala Gly 100 105 110 Asp Ala Glu Ser Arg Val Phe Tyr Leu Lys Met Lys Gly Asp Tyr Tyr 115 120 125 Arg Tyr Leu Ala Glu Val Ala Thr Gly Asp Asp Lys Lys Arg Ile Ile 130 135 140 Asp Ser Ala Arg Ser Ala Tyr Gln Glu Ala Met Asp Ile Ser Lys Lys 145 150 155 160 Glu Met Pro Pro Thr Asn Pro Ile Arg Leu Gly Leu Ala Leu Asn Phe 165 170 175 Ser Val Phe His Tyr Glu Ile Ala Asn Ser Pro Glu Glu Ala Ile Ser 180 185 190 Leu Ala Lys Thr Thr Phe Asp Glu Ala Met Ala Asp Leu His Thr Leu 195 200 205 Ser Glu Asp Ser Tyr Lys Asp Ser Thr Leu Ile Met Gln Leu Leu Arg 210 215 220 Asp Asn Leu Thr Leu Trp Thr Ala Asp Asn Ala Gly Glu Glu Gly Gly 225 230 235 240 Glu Ala Pro Gln Glu Pro Gln Ser 245 <210> 1029 <211> 1474 <212> PRT <213> Homo sapiens <400> 1029 Met Gly Lys Asn Lys Leu Leu His Pro Ser Leu Val Leu Leu Leu Leu 1 5 10 15 Val Leu Leu Pro Thr Asp Ala Ser Val Ser Gly Lys Pro Gln Tyr Met 20 25 30 Val Leu Val Pro Ser Leu Leu His Thr Glu Thr Thr Glu Lys Gly Cys 35 40 45 Val Leu Leu Ser Tyr Leu Asn Glu Thr Val Thr Val Ser Ala Ser Leu 50 55 60 Glu Ser Val Arg Gly Asn Arg Ser Leu Phe Thr Asp Leu Glu Ala Glu 65 70 75 80 Asn Asp Val Leu His Cys Val Ala Phe Ala Val Pro Lys Ser Ser Ser 85 90 95 Asn Glu Glu Val Met Phe Leu Thr Val Gln Val Lys Gly Pro Thr Gln 100 105 110 Glu Phe Lys Lys Arg Thr Thr Val Met Val Lys Asn Glu Asp Ser Leu 115 120 125 Val Phe Val Gln Thr Asp Lys Ser Ile Tyr Lys Pro Gly Gln Thr Val 130 135 140 Lys Phe Arg Val Val Ser Met Asp Glu Asn Phe His Pro Leu Asn Glu 145 150 155 160 Leu Ile Pro Leu Val Tyr Ile Gln Asp Pro Lys Gly Asn Arg Ile Ala 165 170 175 Gln Trp Gln Ser Phe Gln Leu Glu Gly Gly Leu Lys Gln Phe Ser Phe 180 185 190 Pro Leu Ser Ser Glu Pro Phe Gln Gly Ser Tyr Lys Val Val Val Gln 195 200 205 Lys Lys Ser Gly Gly Arg Thr Glu His Pro Phe Thr Val Glu Glu Phe 210 215 220 Val Leu Pro Lys Phe Glu Val Gln Val Thr Val Pro Lys Ile Ile Thr 225 230 235 240 Ile Leu Glu Glu Glu Met Asn Val Ser Val Cys Gly Leu Tyr Thr Tyr 245 250 255 Gly Lys Pro Val Pro Gly His Val Thr Val Ser Ile Cys Arg Lys Tyr 260 265 270 Ser Asp Ala Ser Asp Cys His Gly Glu Asp Ser Gln Ala Phe Cys Glu 275 280 285 Lys Phe Ser Gly Gln Leu Asn Ser His Gly Cys Phe Tyr Gln Gln Val 290 295 300 Lys Thr Lys Val Phe Gln Leu Lys Arg Lys Glu Tyr Glu Met Lys Leu 305 310 315 320 His Thr Glu Ala Gln Ile Gln Glu Glu Gly Thr Val Val Glu Leu Thr 325 330 335 Gly Arg Gln Ser Ser Glu Ile Thr Arg Thr Ile Thr Lys Leu Ser Phe 340 345 350 Val Lys Val Asp Ser His Phe Arg Gln Gly Ile Pro Phe Phe Gly Gln 355 360 365 Val Arg Leu Val Asp Gly Lys Gly Val Pro Ile Pro Asn Lys Val Ile 370 375 380 Phe Ile Arg Gly Asn Glu Ala Asn Tyr Tyr Ser Asn Ala Thr Thr Asp 385 390 395 400 Glu His Gly Leu Val Gln Phe Ser Ile Asn Thr Thr Asn Val Met Gly 405 410 415 Thr Ser Leu Thr Val Arg Val Asn Tyr Lys Asp Arg Ser Pro Cys Tyr 420 425 430 Gly Tyr Gln Trp Val Ser Glu Glu His Glu Glu Ala His His Thr Ala 435 440 445 Tyr Leu Val Phe Ser Pro Ser Lys Ser Phe Val His Leu Glu Pro Met 450 455 460 Ser His Glu Leu Pro Cys Gly His Thr Gln Thr Val Gln Ala His Tyr 465 470 475 480 Ile Leu Asn Gly Gly Thr Leu Leu Gly Leu Lys Lys Leu Ser Phe Tyr 485 490 495 Tyr Leu Ile Met Ala Lys Gly Gly Ile Val Arg Thr Gly Thr His Gly 500 505 510 Leu Leu Val Lys Gln Glu Asp Met Lys Gly His Phe Ser Ile Ser Ile 515 520 525 Pro Val Lys Ser Asp Ile Ala Pro Val Ala Arg Leu Leu Ile Tyr Ala 530 535 540 Val Leu Pro Thr Gly Asp Val Ile Gly Asp Ser Ala Lys Tyr Asp Val 545 550 555 560 Glu Asn Cys Leu Ala Asn Lys Val Asp Leu Ser Phe Ser Pro Ser Gln 565 570 575 Ser Leu Pro Ala Ser His Ala His Leu Arg Val Thr Ala Ala Pro Gln 580 585 590 Ser Val Cys Ala Leu Arg Ala Val Asp Gln Ser Val Leu Leu Met Lys 595 600 605 Pro Asp Ala Glu Leu Ser Ala Ser Ser Val Tyr Asn Leu Leu Pro Glu 610 615 620 Lys Asp Leu Thr Gly Phe Pro Gly Pro Leu Asn Asp Gln Asp Asn Glu 625 630 635 640 Asp Cys Ile Asn Arg His Asn Val Tyr Ile Asn Gly Ile Thr Tyr Thr 645 650 655 Pro Val Ser Ser Thr Asn Glu Lys Asp Met Tyr Ser Phe Leu Glu Asp 660 665 670 Met Gly Leu Lys Ala Phe Thr Asn Ser Lys Ile Arg Lys Pro Lys Met 675 680 685 Cys Pro Gln Leu Gln Gln Tyr Glu Met His Gly Pro Glu Gly Leu Arg 690 695 700 Val Gly Phe Tyr Glu Ser Asp Val Met Gly Arg Gly His Ala Arg Leu 705 710 715 720 Val His Val Glu Glu Pro His Thr Glu Thr Val Arg Lys Tyr Phe Pro 725 730 735 Glu Thr Trp Ile Trp Asp Leu Val Val Val Asn Ser Ala Gly Val Ala 740 745 750 Glu Val Gly Val Thr Val Pro Asp Thr Ile Thr Glu Trp Lys Ala Gly 755 760 765 Ala Phe Cys Leu Ser Glu Asp Ala Gly Leu Gly Ile Ser Ser Thr Ala 770 775 780 Ser Leu Arg Ala Phe Gln Pro Phe Phe Val Glu Leu Thr Met Pro Tyr 785 790 795 800 Ser Val Ile Arg Gly Glu Ala Phe Thr Leu Lys Ala Thr Val Leu Asn 805 810 815 Tyr Leu Pro Lys Cys Ile Arg Val Ser Val Gln Leu Glu Ala Ser Pro 820 825 830 Ala Phe Leu Ala Val Pro Val Glu Lys Glu Gln Ala Pro His Cys Ile 835 840 845 Cys Ala Asn Gly Arg Gln Thr Val Ser Trp Ala Val Thr Pro Lys Ser 850 855 860 Leu Gly Asn Val Asn Phe Thr Val Ser Ala Glu Ala Leu Glu Ser Gln 865 870 875 880 Glu Leu Cys Gly Thr Glu Val Pro Ser Val Pro Glu His Gly Arg Lys 885 890 895 Asp Thr Val Ile Lys Pro Leu Leu Val Glu Pro Glu Gly Leu Glu Lys 900 905 910 Glu Thr Thr Phe Asn Ser Leu Leu Cys Pro Ser Gly Gly Glu Val Ser 915 920 925 Glu Glu Leu Ser Leu Lys Leu Pro Pro Asn Val Val Glu Glu Ser Ala 930 935 940 Arg Ala Ser Val Ser Val Leu Gly Asp Ile Leu Gly Ser Ala Met Gln 945 950 955 960 Asn Thr Gln Asn Leu Leu Gln Met Pro Tyr Gly Cys Gly Glu Gln Asn 965 970 975 Met Val Leu Phe Ala Pro Asn Ile Tyr Val Leu Asp Tyr Leu Asn Glu 980 985 990 Thr Gln Gln Leu Thr Pro Glu Ile Lys Ser Lys Ala Ile Gly Tyr Leu 995 1000 1005 Asn Thr Gly Tyr Gln Arg Gln Leu Asn Tyr Lys His Tyr Asp Gly 1010 1015 1020 Ser Tyr Ser Thr Phe Gly Glu Arg Tyr Gly Arg Asn Gln Gly Asn 1025 1030 1035 Thr Trp Leu Thr Ala Phe Val Leu Lys Thr Phe Ala Gln Ala Arg 1040 1045 1050 Ala Tyr Ile Phe Ile Asp Glu Ala His Ile Thr Gln Ala Leu Ile 1055 1060 1065 Trp Leu Ser Gln Arg Gln Lys Asp Asn Gly Cys Phe Arg Ser Ser 1070 1075 1080 Gly Ser Leu Leu Asn Asn Ala Ile Lys Gly Gly Val Glu Asp Glu 1085 1090 1095 Val Thr Leu Ser Ala Tyr Ile Thr Ile Ala Leu Leu Glu Ile Pro 1100 1105 1110 Leu Thr Val Thr His Pro Val Val Arg Asn Ala Leu Phe Cys Leu 1115 1120 1125 Glu Ser Ala Trp Lys Thr Ala Gln Glu Gly Asp His Gly Ser His 1130 1135 1140 Val Tyr Thr Lys Ala Leu Leu Ala Tyr Ala Phe Ala Leu Ala Gly 1145 1150 1155 Asn Gln Asp Lys Arg Lys Glu Val Leu Lys Ser Leu Asn Glu Glu 1160 1165 1170 Ala Val Lys Lys Asp Asn Ser Val His Trp Glu Arg Pro Gln Lys 1175 1180 1185 Pro Lys Ala Pro Val Gly His Phe Tyr Glu Pro Gln Ala Pro Ser 1190 1195 1200 Ala Glu Val Glu Met Thr Ser Tyr Val Leu Leu Ala Tyr Leu Thr 1205 1210 1215 Ala Gln Pro Ala Pro Thr Ser Glu Asp Leu Thr Ser Ala Thr Asn 1220 1225 1230 Ile Val Lys Trp Ile Thr Lys Gln Gln Asn Ala Gln Gly Gly Phe 1235 1240 1245 Ser Ser Thr Gln Asp Thr Val Val Ala Leu His Ala Leu Ser Lys 1250 1255 1260 Tyr Gly Ala Ala Thr Phe Thr Arg Thr Gly Lys Ala Ala Gln Val 1265 1270 1275 Thr Ile Gln Ser Ser Gly Thr Phe Ser Ser Lys Phe Gln Val Asp 1280 1285 1290 Asn Asn Asn Arg Leu Leu Leu Gln Gln Val Ser Leu Pro Glu Leu 1295 1300 1305 Pro Gly Glu Tyr Ser Met Lys Val Thr Gly Glu Gly Cys Val Tyr 1310 1315 1320 Leu Gln Thr Ser Leu Lys Tyr Asn Ile Leu Pro Glu Lys Glu Glu 1325 1330 1335 Phe Pro Phe Ala Leu Gly Val Gln Thr Leu Pro Gln Thr Cys Asp 1340 1345 1350 Glu Pro Lys Ala His Thr Ser Phe Gln Ile Ser Leu Ser Val Ser 1355 1360 1365 Tyr Thr Gly Ser Arg Ser Ala Ser Asn Met Ala Ile Val Asp Val 1370 1375 1380 Lys Met Val Ser Gly Phe Ile Pro Leu Lys Pro Thr Val Lys Met 1385 1390 1395 Leu Glu Arg Ser Asn His Val Ser Arg Thr Glu Val Ser Ser Asn 1400 1405 1410 His Val Leu Ile Tyr Leu Asp Lys Val Ser Asn Gln Thr Leu Ser 1415 1420 1425 Leu Phe Phe Thr Val Leu Gln Asp Val Pro Val Arg Asp Leu Lys 1430 1435 1440 Pro Ala Ile Val Lys Val Tyr Asp Tyr Tyr Glu Thr Asp Glu Phe 1445 1450 1455 Ala Ile Ala Glu Tyr Asn Ala Pro Cys Ser Lys Asp Leu Gly Asn 1460 1465 1470 Ala <210> 1030 <211> 147 <212> PRT <213> Homo sapiens <400> 1030 Met Ala Ser His Arg Leu Leu Leu Leu Cys Leu Ala Gly Leu Val Phe 1 5 10 15 Val Ser Glu Ala Gly Pro Thr Gly Thr Gly Glu Ser Lys Cys Pro Leu 20 25 30 Met Val Lys Val Leu Asp Ala Val Arg Gly Ser Pro Ala Ile Asn Val 35 40 45 Ala Val His Val Phe Arg Lys Ala Ala Asp Asp Thr Trp Glu Pro Phe 50 55 60 Ala Ser Gly Lys Thr Ser Glu Ser Gly Glu Leu His Gly Leu Thr Thr 65 70 75 80 Glu Glu Glu Phe Val Glu Gly Ile Tyr Lys Val Glu Ile Asp Thr Lys 85 90 95 Ser Tyr Trp Lys Ala Leu Gly Ile Ser Pro Phe His Glu His Ala Glu 100 105 110 Val Val Phe Thr Ala Asn Asp Ser Gly Pro Arg Arg Tyr Thr Ile Ala 115 120 125 Ala Leu Leu Ser Pro Tyr Ser Tyr Ser Thr Thr Ala Val Val Thr Asn 130 135 140 Pro Lys Glu 145 <210> 1031 <211> 527 <212> PRT <213> Homo sapiens <400> 1031 Met Tyr Ala Leu Phe Leu Leu Ala Ser Leu Leu Gly Ala Ala Leu Ala 1 5 10 15 Gly Pro Val Leu Gly Leu Lys Glu Cys Thr Arg Gly Ser Ala Val Trp 20 25 30 Cys Gln Asn Val Lys Thr Ala Ser Asp Cys Gly Ala Val Lys His Cys 35 40 45 Leu Gln Thr Val Trp Asn Lys Pro Thr Val Lys Ser Leu Pro Cys Asp 50 55 60 Ile Cys Lys Asp Val Val Thr Ala Ala Gly Asp Met Leu Lys Asp Asn 65 70 75 80 Ala Thr Glu Glu Glu Ile Leu Val Tyr Leu Glu Lys Thr Cys Asp Trp 85 90 95 Leu Pro Lys Pro Asn Met Ser Ala Ser Cys Lys Glu Ile Val Asp Ser 100 105 110 Tyr Leu Pro Val Ile Leu Asp Ile Ile Lys Gly Glu Met Ser Arg Pro 115 120 125 Gly Glu Val Cys Ser Ala Leu Asn Leu Cys Glu Ser Leu Gln Lys His 130 135 140 Leu Ala Glu Leu Asn His Gln Lys Gln Leu Glu Ser Asn Lys Ile Pro 145 150 155 160 Glu Leu Asp Met Thr Glu Val Val Ala Pro Phe Met Ala Asn Ile Pro 165 170 175 Leu Leu Leu Tyr Pro Gln Asp Gly Pro Arg Ser Lys Pro Gln Pro Lys 180 185 190 Asp Asn Gly Asp Val Cys Gln Asp Cys Ile Gln Met Val Thr Asp Ile 195 200 205 Gln Thr Ala Val Arg Thr Asn Ser Thr Phe Val Gln Ala Leu Val Glu 210 215 220 His Val Lys Glu Glu Cys Asp Arg Leu Gly Pro Gly Met Ala Asp Ile 225 230 235 240 Cys Lys Asn Tyr Ile Ser Gln Tyr Ser Glu Ile Ala Ile Gln Met Met 245 250 255 Met His Met Ser Leu Gln Gln Pro Lys Glu Ile Cys Ala Leu Val Gly 260 265 270 Phe Cys Asp Glu Val Lys Glu Met Pro Met Gln Thr Leu Val Pro Ala 275 280 285 Lys Val Ala Ser Lys Asn Val Ile Pro Ala Leu Glu Leu Val Glu Pro 290 295 300 Ile Lys Lys His Glu Val Pro Ala Lys Ser Asp Val Tyr Cys Glu Val 305 310 315 320 Cys Glu Phe Leu Val Lys Glu Val Thr Lys Leu Ile Asp Asn Asn Lys 325 330 335 Thr Glu Lys Glu Ile Leu Asp Ala Phe Asp Lys Met Cys Ser Lys Leu 340 345 350 Pro Lys Ser Leu Ser Glu Glu Cys Gln Glu Val Val Asp Thr Tyr Gly 355 360 365 Ser Ser Ile Leu Ser Ile Leu Leu Glu Glu Val Ser Pro Glu Leu Val 370 375 380 Cys Ser Met Leu His Leu Cys Ser Gly Thr Arg Leu Pro Ala Leu Thr 385 390 395 400 Val His Val Thr Gln Pro Lys Asp Gly Gly Phe Cys Glu Val Cys Lys 405 410 415 Lys Leu Val Gly Tyr Leu Asp Arg Asn Leu Glu Lys Asn Ser Thr Lys 420 425 430 Gln Glu Ile Leu Ala Ala Leu Glu Lys Gly Cys Ser Phe Leu Pro Asp 435 440 445 Pro Tyr Gln Lys Gln Cys Asp Gln Phe Val Ala Glu Tyr Glu Pro Val 450 455 460 Leu Ile Glu Ile Leu Val Glu Val Met Asp Pro Ser Phe Val Cys Leu 465 470 475 480 Lys Ile Gly Ala Cys Pro Ser Ala His Lys Pro Leu Leu Gly Thr Glu 485 490 495 Lys Cys Ile Trp Gly Pro Ser Tyr Trp Cys Gln Asn Thr Glu Thr Ala 500 505 510 Ala Gln Cys Asn Ala Val Glu His Cys Lys Arg His Val Trp Asn 515 520 525 <210> 1032 <211> 426 <212> PRT <213> Homo sapiens <400> 1032 Met Phe Trp Glu Val Ile Ser Asp Glu His Gly Ile Asp Pro Thr Gly 1 5 10 15 Thr Tyr His Gly Asp Ser Asp Leu Gln Leu Asp Arg Ile Ser Val Tyr 20 25 30 Tyr Asn Glu Ala Thr Gly Gly Lys Tyr Val Pro Arg Ala Ile Leu Val 35 40 45 Asp Leu Glu Pro Gly Thr Met Asp Ser Val Arg Ser Gly Pro Phe Gly 50 55 60 Gln Ile Phe Arg Pro Asp Asn Phe Val Phe Gly Gln Ser Gly Ala Gly 65 70 75 80 Asn Asn Trp Ala Lys Gly His Tyr Thr Glu Gly Ala Glu Leu Val Asp 85 90 95 Ser Val Leu Asp Val Val Arg Lys Glu Ala Glu Ser Cys Asp Cys Leu 100 105 110 Gln Gly Phe Gln Leu Thr His Ser Leu Gly Gly Gly Thr Gly Ser Gly 115 120 125 Met Gly Thr Leu Leu Ile Ser Lys Ile Arg Glu Glu Tyr Pro Asp Arg 130 135 140 Ile Met Asn Thr Phe Ser Val Val Pro Ser Pro Lys Val Ser Asp Thr 145 150 155 160 Val Val Glu Pro Tyr Asn Ala Thr Leu Ser Val His Gln Leu Val Glu 165 170 175 Asn Thr Asp Glu Thr Tyr Cys Ile Asp Asn Glu Ala Leu Tyr Asp Ile 180 185 190 Cys Phe Arg Thr Leu Lys Leu Thr Thr Pro Thr Tyr Gly Asp Leu Asn 195 200 205 His Leu Val Ser Ala Thr Met Ser Gly Val Thr Thr Cys Leu Arg Phe 210 215 220 Pro Gly Gln Leu Asn Ala Asp Leu Arg Lys Leu Ala Val Asn Met Val 225 230 235 240 Pro Phe Pro Arg Leu His Phe Phe Met Pro Gly Phe Ala Pro Leu Thr 245 250 255 Ser Arg Gly Ser Gln Gln Tyr Arg Ala Leu Thr Val Pro Glu Leu Thr 260 265 270 Gln Gln Val Phe Asp Ala Lys Asn Met Met Ala Ala Cys Asp Pro Arg 275 280 285 His Gly Arg Tyr Leu Thr Val Ala Ala Val Phe Arg Gly Arg Met Ser 290 295 300 Met Lys Glu Val Asp Glu Gln Met Leu Asn Val Gln Asn Lys Asn Ser 305 310 315 320 Ser Tyr Phe Val Glu Trp Ile Pro Asn Asn Val Lys Thr Ala Val Cys 325 330 335 Asp Ile Pro Pro Arg Gly Leu Lys Met Ala Val Thr Phe Ile Gly Asn 340 345 350 Ser Thr Ala Ile Gln Glu Leu Phe Lys Arg Ile Ser Glu Gln Phe Thr 355 360 365 Ala Met Phe Arg Arg Lys Ala Phe Leu His Trp Tyr Thr Gly Glu Gly 370 375 380 Met Asp Glu Met Glu Phe Thr Glu Ala Glu Ser Asn Met Asn Asp Leu 385 390 395 400 Val Ser Glu Tyr Gln Gln Tyr Gln Asp Ala Thr Ala Glu Glu Glu Glu 405 410 415 Asp Phe Gly Glu Glu Ala Glu Glu Glu Ala 420 425 <210> 1033 <211> 117 <212> PRT <213> Homo sapiens <400> 1033 Met Ala Trp Thr Val Leu Leu Leu Gly Leu Leu Ser His Cys Thr Gly 1 5 10 15 Ser Val Thr Ser Tyr Val Leu Thr Gln Pro Pro Ser Val Ser Val Ala 20 25 30 Pro Gly Gln Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Gly Ser 35 40 45 Lys Ser Val His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu 50 55 60 Val Val Tyr Asp Asp Ser Asp Arg Pro Ser Gly Ile Pro Glu Arg Phe 65 70 75 80 Ser Gly Ser Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Val 85 90 95 Glu Ala Gly Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Ser 100 105 110 Ser Asp His Pro Thr 115 <210> 1034 <211> 109 <212> PRT <213> Homo sapiens <400> 1034 Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 1 5 10 15 Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Asn Ser 20 25 30 Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 35 40 45 Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 50 55 60 Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 65 70 75 80 Pro Asp Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro 85 90 95 Gln Thr Phe Gly Gln Gly Ser Lys Val Glu Ile Lys Arg 100 105 <210> 1035 <211> 129 <212> PRT <213> Homo sapiens <400> 1035 Met Glu Thr Pro Ala Gln Leu Leu Phe Leu Leu Leu Leu Trp Leu Pro 1 5 10 15 Asp Thr Thr Gly Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser 20 25 30 Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser 35 40 45 Val Ser Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala 50 55 60 Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro 65 70 75 80 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 85 90 95 Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr 100 105 110 Gly Thr Ser Pro Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 115 120 125 Arg <210> 1036 <211> 22 <212> PRT <213> Homo sapiens <400> 1036 Ala Ser Gln Ser Val Ser Asn Ser Tyr Leu Ala Trp Tyr Gln Gln Lys 1 5 10 15 Pro Gly Gln Ala Pro Arg 20 <210> 1037 <211> 23 <212> PRT <213> Homo sapiens <400> 1037 Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 1 5 10 15 Phe Thr Leu Thr Ile Ser Arg 20 <210> 1038 <211> 18 <212> PRT <213> Homo sapiens <400> 1038 Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 1 5 10 15 Glu Arg <210> 1039 <211> 24 <212> PRT <213> Homo sapiens <400> 1039 Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 1 5 10 15 Glu Arg Ala Thr Leu Ser Cys Arg 20 <210> 1040 <211> 16 <212> PRT <213> Homo sapiens <400> 1040 Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg 1 5 10 15 <210> 1041 <211> 9 <212> PRT <213> Homo sapiens <400> 1041 Leu Leu Ile Tyr Gly Ala Ser Ser Arg 1 5 <210> 1042 <211> 16 <212> PRT <213> Homo sapiens <400> 1042 Phe Ser Gly Ser Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg 1 5 10 15 <210> 1043 <211> 30 <212> PRT <213> Homo sapiens <400> 1043 Ser Val His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val 1 5 10 15 Val Tyr Asp Asp Ser Asp Arg Pro Ser Gly Ile Pro Glu Arg 20 25 30 <210> 1044 <211> 15 <212> PRT <213> Homo sapiens <400> 1044 Ala Leu Thr Val Pro Glu Leu Thr Gln Gln Val Phe Asp Ala Lys 1 5 10 15 <210> 1045 <211> 19 <212> PRT <213> Homo sapiens <400> 1045 Gly His Tyr Thr Glu Gly Ala Glu Leu Val Asp Ser Val Leu Asp Val 1 5 10 15 Val Arg Lys <210> 1046 <211> 14 <212> PRT <213> Homo sapiens <400> 1046 Asn Ser Ser Tyr Phe Val Glu Trp Ile Pro Asn Asn Val Lys 1 5 10 <210> 1047 <211> 26 <212> PRT <213> Homo sapiens <400> 1047 Ser Gly Pro Phe Gly Gln Ile Phe Arg Pro Asp Asn Phe Val Phe Gly 1 5 10 15 Gln Ser Gly Ala Gly Asn Asn Trp Ala Lys 20 25 <210> 1048 <211> 9 <212> PRT <213> Homo sapiens <400> 1048 Tyr Leu Thr Val Ala Ala Val Phe Arg 1 5 <210> 1049 <211> 12 <212> PRT <213> Homo sapiens <400> 1049 Asp Ile Ala Pro Thr Leu Thr Leu Tyr Val Gly Lys 1 5 10 <210> 1050 <211> 13 <212> PRT <213> Homo sapiens <400> 1050 Asp Ile Ala Pro Thr Leu Thr Leu Tyr Val Gly Lys Lys 1 5 10 <210> 1051 <211> 6 <212> PRT <213> Homo sapiens <400> 1051 Phe Thr Asp His Leu Lys 1 5 <210> 1052 <211> 10 <212> PRT <213> Homo sapiens <400> 1052 His Tyr Glu Gly Ser Thr Val Pro Glu Lys 1 5 10 <210> 1053 <211> 15 <212> PRT <213> Homo sapiens <400> 1053 Leu Arg Thr Glu Gly Asp Gly Val Tyr Thr Leu Asn Asn Glu Lys 1 5 10 15 <210> 1054 <211> 20 <212> PRT <213> Homo sapiens <400> 1054 Leu Arg Thr Glu Gly Asp Gly Val Tyr Thr Leu Asn Asn Glu Lys Gln 1 5 10 15 Trp Ile Asn Lys 20 <210> 1055 <211> 7 <212> PRT <213> Homo sapiens <400> 1055 Gln Leu Val Glu Ile Glu Lys 1 5 <210> 1056 <211> 13 <212> PRT <213> Homo sapiens <400> 1056 Thr Glu Gly Asp Gly Val Tyr Thr Leu Asn Asn Glu Lys 1 5 10 <210> 1057 <211> 18 <212> PRT <213> Homo sapiens <400> 1057 Thr Glu Gly Asp Gly Val Tyr Thr Leu Asn Asn Glu Lys Gln Trp Ile 1 5 10 15 Asn Lys <210> 1058 <211> 9 <212> PRT <213> Homo sapiens <400> 1058 Val Gly Tyr Val Ser Gly Trp Gly Arg 1 5 <210> 1059 <211> 16 <212> PRT <213> Homo sapiens <400> 1059 Val Val Leu His Pro Asn Tyr Ser Gln Val Asp Ile Gly Leu Ile Lys 1 5 10 15 <210> 1060 <211> 8 <212> PRT <213> Homo sapiens <400> 1060 Tyr Gln Cys Lys Asn Tyr Tyr Lys 1 5 <210> 1061 <211> 10 <212> PRT <213> Homo sapiens <400> 1061 Tyr Gln Cys Lys Asn Tyr Tyr Lys Leu Arg 1 5 10 <210> 1062 <211> 14 <212> PRT <213> Homo sapiens <400> 1062 Tyr Val Met Leu Pro Val Ala Asp Gln Asp Gln Cys Ile Arg 1 5 10 <210> 1063 <211> 222 <212> PRT <213> Homo sapiens <400> 1063 Met Ser Ala Leu Gly Ala Val Ile Ala Leu Leu Leu Trp Gly Gln Leu 1 5 10 15 Phe Ala Val Asp Ser Gly Asn Asp Val Thr Asp Ile Ala Asp Asp Gly 20 25 30 Cys Pro Lys Pro Pro Glu Ile Ala His Gly Tyr Val Glu His Ser Val 35 40 45 Arg Tyr Gln Cys Lys Asn Tyr Tyr Lys Leu Arg Thr Glu Gly Asp Gly 50 55 60 Val Tyr Thr Leu Asn Asn Glu Lys Gln Trp Ile Asn Lys Ala Val Gly 65 70 75 80 Asp Lys Leu Pro Glu Cys Glu Ala Gly Ala Thr Leu Ile Asn Glu Gln 85 90 95 Trp Leu Leu Thr Thr Ala Lys Asn Leu Phe Leu Asn His Ser Glu Asn 100 105 110 Ala Thr Ala Lys Asp Ile Ala Pro Thr Leu Thr Leu Tyr Val Gly Lys 115 120 125 Lys Gln Leu Val Glu Ile Glu Lys Val Val Leu His Pro Asn Tyr Ser 130 135 140 Gln Val Asp Ile Gly Leu Ile Lys Leu Lys Gln Lys Val Ser Val Asn 145 150 155 160 Glu Arg Val Met Pro Ile Cys Leu Pro Ser Lys Asp Tyr Ala Glu Val 165 170 175 Gly Arg Val Gly Tyr Val Ser Gly Trp Gly Arg Asn Ala Asn Phe Lys 180 185 190 Phe Thr Asp His Leu Lys Tyr Val Met Leu Pro Val Ala Asp Gln Asp 195 200 205 Gln Cys Ile Arg His Tyr Glu Gly Ser Thr Val Pro Glu Lys 210 215 220 <210> 1064 <211> 31 <212> PRT <213> Homo sapiens <400> 1064 Ala Val Gly Asp Lys Leu Pro Glu Cys Glu Ala Asp Asp Gly Cys Pro 1 5 10 15 Lys Pro Pro Glu Ile Ala His Gly Tyr Val Glu His Ser Val Arg 20 25 30 <210> 1065 <211> 17 <212> PRT <213> Homo sapiens <400> 1065 Ala Val Gly Asp Lys Leu Pro Glu Cys Glu Ala Val Cys Gly Lys Pro 1 5 10 15 Lys <210> 1066 <211> 12 <212> PRT <213> Homo sapiens <400> 1066 Asp Ile Ala Pro Thr Leu Thr Leu Tyr Val Gly Lys 1 5 10 <210> 1067 <211> 13 <212> PRT <213> Homo sapiens <400> 1067 Asp Ile Ala Pro Thr Leu Thr Leu Tyr Val Gly Lys Lys 1 5 10 <210> 1068 <211> 6 <212> PRT <213> Homo sapiens <400> 1068 Phe Thr Asp His Leu Lys 1 5 <210> 1069 <211> 8 <212> PRT <213> Homo sapiens <400> 1069 Gly Ser Phe Pro Trp Gln Ala Lys 1 5 <210> 1070 <211> 10 <212> PRT <213> Homo sapiens <400> 1070 His Tyr Glu Gly Ser Thr Val Pro Glu Lys 1 5 10 <210> 1071 <211> 11 <212> PRT <213> Homo sapiens <400> 1071 His Tyr Glu Gly Ser Thr Val Pro Glu Lys Lys 1 5 10 <210> 1072 <211> 9 <212> PRT <213> Homo sapiens <400> 1072 Ile Leu Gly Gly His Leu Asp Ala Lys 1 5 <210> 1073 <211> 17 <212> PRT <213> Homo sapiens <400> 1073 Ile Leu Gly Gly His Leu Asp Ala Lys Gly Ser Phe Pro Trp Gln Ala 1 5 10 15 Lys <210> 1074 <211> 14 <212> PRT <213> Homo sapiens <400> 1074 Leu Arg Thr Glu Gly Asp Gly Val Tyr Thr Leu Asn Asp Lys 1 5 10 <210> 1075 <211> 15 <212> PRT <213> Homo sapiens <400> 1075 Leu Arg Thr Glu Gly Asp Gly Val Tyr Thr Leu Asn Asp Lys Lys 1 5 10 15 <210> 1076 <211> 15 <212> PRT <213> Homo sapiens <400> 1076 Leu Arg Thr Glu Gly Asp Gly Val Tyr Thr Leu Asn Asn Glu Lys 1 5 10 15 <210> 1077 <211> 20 <212> PRT <213> Homo sapiens <400> 1077 Leu Arg Thr Glu Gly Asp Gly Val Tyr Thr Leu Asn Asn Glu Lys Gln 1 5 10 15 Trp Ile Asn Lys 20 <210> 1078 <211> 8 <212> PRT <213> Homo sapiens <400> 1078 Asn Pro Ala Asn Pro Val Gln Arg 1 5 <210> 1079 <211> 7 <212> PRT <213> Homo sapiens <400> 1079 Gln Leu Val Glu Ile Glu Lys 1 5 <210> 1080 <211> 12 <212> PRT <213> Homo sapiens <400> 1080 Ser Cys Ala Val Ala Glu Tyr Gly Val Tyr Val Lys 1 5 10 <210> 1081 <211> 20 <212> PRT <213> Homo sapiens <400> 1081 Ser Pro Val Gly Val Gln Pro Ile Leu Asn Glu His Thr Phe Cys Ala 1 5 10 15 Gly Met Ser Lys 20 <210> 1082 <211> 12 <212> PRT <213> Homo sapiens <400> 1082 Thr Glu Gly Asp Gly Val Tyr Thr Leu Asn Asp Lys 1 5 10 <210> 1083 <211> 18 <212> PRT <213> Homo sapiens <400> 1083 Thr Glu Gly Asp Gly Val Tyr Thr Leu Asn Asp Lys Lys Gln Trp Ile 1 5 10 15 Asn Lys <210> 1084 <211> 13 <212> PRT <213> Homo sapiens <400> 1084 Thr Glu Gly Asp Gly Val Tyr Thr Leu Asn Asn Glu Lys 1 5 10 <210> 1085 <211> 18 <212> PRT <213> Homo sapiens <400> 1085 Thr Glu Gly Asp Gly Val Tyr Thr Leu Asn Asn Glu Lys Gln Trp Ile 1 5 10 15 Asn Lys <210> 1086 <211> 9 <212> PRT <213> Homo sapiens <400> 1086 Val Gly Tyr Val Ser Gly Trp Gly Arg 1 5 <210> 1087 <211> 17 <212> PRT <213> Homo sapiens <400> 1087 Glu Ile Val His Leu Gln Ala Gly Gln Cys Gly Asn Gln Ile Gly Ala 1 5 10 15 Lys <210> 1088 <211> 18 <212> PRT <213> Homo sapiens <400> 1088 Gly His Tyr Thr Glu Gly Ala Glu Leu Val Asp Ser Val Leu Asp Val 1 5 10 15 Val Arg <210> 1089 <211> 19 <212> PRT <213> Homo sapiens <400> 1089 Gly His Tyr Thr Glu Gly Ala Glu Leu Val Asp Ser Val Leu Asp Val 1 5 10 15 Val Arg Lys <210> 1090 <211> 16 <212> PRT <213> Homo sapiens <400> 1090 Ile Asn Val Tyr Tyr Asn Glu Ala Thr Gly Gly Lys Tyr Val Pro Arg 1 5 10 15 <210> 1091 <211> 14 <212> PRT <213> Homo sapiens <400> 1091 Asn Ser Ser Tyr Phe Val Glu Trp Ile Pro Asn Asn Val Lys 1 5 10 <210> 1092 <211> 26 <212> PRT <213> Homo sapiens <400> 1092 Ser Gly Pro Phe Gly Gln Ile Phe Arg Pro Asp Asn Phe Val Phe Gly 1 5 10 15 Gln Ser Gly Ala Gly Asn Asn Trp Ala Lys 20 25 <210> 1093 <211> 9 <212> PRT <213> Homo sapiens <400> 1093 Tyr Leu Thr Val Ala Ala Val Phe Arg 1 5 <210> 1094 <211> 445 <212> PRT <213> Homo sapiens <400> 1094 Met Arg Glu Ile Val His Leu Gln Ala Gly Gln Cys Gly Asn Gln Ile 1 5 10 15 Gly Ala Lys Phe Trp Glu Val Ile Ser Asp Glu His Gly Ile Asp Pro 20 25 30 Thr Gly Thr Tyr His Gly Asp Ser Asp Leu Gln Leu Glu Arg Ile Asn 35 40 45 Val Tyr Tyr Asn Glu Ala Thr Gly Gly Lys Tyr Val Pro Arg Ala Val 50 55 60 Leu Val Asp Leu Glu Pro Gly Thr Met Asp Ser Val Arg Ser Gly Pro 65 70 75 80 Phe Gly Gln Ile Phe Arg Pro Asp Asn Phe Val Phe Gly Gln Ser Gly 85 90 95 Ala Gly Asn Asn Trp Ala Lys Gly His Tyr Thr Glu Gly Ala Glu Leu 100 105 110 Val Asp Ser Val Leu Asp Val Val Arg Lys Glu Ala Glu Ser Cys Asp 115 120 125 Cys Leu Gln Gly Phe Gln Leu Thr His Ser Leu Gly Gly Gly Thr Gly 130 135 140 Ser Gly Met Gly Thr Leu Leu Ile Ser Lys Ile Arg Glu Glu Tyr Pro 145 150 155 160 Asp Arg Ile Met Asn Thr Phe Ser Val Val Pro Ser Pro Lys Val Ser 165 170 175 Asp Thr Val Val Glu Pro Tyr Asn Ala Thr Leu Ser Val His Gln Leu 180 185 190 Val Glu Asn Thr Asp Glu Thr Tyr Cys Ile Asp Asn Glu Ala Leu Tyr 195 200 205 Asp Ile Cys Phe Arg Thr Leu Lys Leu Thr Thr Pro Thr Tyr Gly Asp 210 215 220 Leu Asn His Leu Val Ser Ala Thr Met Ser Gly Val Thr Thr Cys Leu 225 230 235 240 Arg Phe Pro Gly Gln Leu Asn Ala Asp Leu Arg Lys Leu Ala Val Asn 245 250 255 Met Val Pro Phe Pro Arg Leu His Phe Phe Met Pro Gly Phe Ala Pro 260 265 270 Leu Thr Ser Arg Gly Ser Gln Gln Tyr Arg Ala Leu Thr Val Pro Glu 275 280 285 Leu Thr Gln Gln Met Phe Asp Ala Lys Asn Met Met Ala Ala Cys Asp 290 295 300 Pro Arg His Gly Arg Tyr Leu Thr Val Ala Ala Val Phe Arg Gly Arg 305 310 315 320 Met Ser Met Lys Glu Val Asp Glu Gln Met Leu Asn Val Gln Asn Lys 325 330 335 Asn Ser Ser Tyr Phe Val Glu Trp Ile Pro Asn Asn Val Lys Thr Ala 340 345 350 Val Cys Asp Ile Pro Pro Arg Gly Leu Lys Met Ser Ala Thr Phe Ile 355 360 365 Gly Asn Ser Thr Ala Ile Gln Glu Leu Phe Lys Arg Ile Ser Glu Gln 370 375 380 Phe Thr Ala Met Phe Arg Arg Lys Ala Phe Leu His Trp Tyr Thr Gly 385 390 395 400 Glu Gly Met Asp Glu Met Glu Phe Thr Glu Ala Glu Ser Asn Met Asn 405 410 415 Asp Leu Val Ser Glu Tyr Gln Gln Tyr Gln Asp Ala Thr Ala Glu Glu 420 425 430 Glu Gly Glu Phe Glu Glu Glu Ala Glu Glu Glu Val Ala 435 440 445 <210> 1095 <211> 15 <212> PRT <213> Homo sapiens <400> 1095 Asp Ala Ser Gly Ala Thr Phe Thr Trp Thr Pro Ser Ser Gly Lys 1 5 10 15 <210> 1096 <211> 24 <212> PRT <213> Homo sapiens <400> 1096 Asp Ala Ser Gly Ala Thr Phe Thr Trp Thr Pro Ser Ser Gly Lys Ser 1 5 10 15 Ala Val Gln Gly Pro Pro Glu Arg 20 <210> 1097 <211> 15 <212> PRT <213> Homo sapiens <400> 1097 Asp Val Leu Val Arg Trp Leu Gln Gly Ser Gln Glu Leu Pro Arg 1 5 10 15 <210> 1098 <211> 17 <212> PRT <213> Homo sapiens <400> 1098 Asp Val Leu Val Arg Trp Leu Gln Gly Ser Gln Glu Leu Pro Arg Glu 1 5 10 15 Lys <210> 1099 <211> 9 <212> PRT <213> Homo sapiens <400> 1099 Glu Lys Tyr Leu Thr Trp Ala Ser Arg 1 5 <210> 1100 <211> 26 <212> PRT <213> Homo sapiens <400> 1100 Glu Lys Tyr Leu Thr Trp Ala Ser Arg Gln Glu Pro Ser Gln Gly Thr 1 5 10 15 Thr Thr Phe Ala Val Thr Ser Ile Leu Arg 20 25 <210> 1101 <211> 20 <212> PRT <213> Homo sapiens <400> 1101 Gly Asp Thr Phe Ser Cys Met Val Gly His Glu Ala Leu Pro Leu Ala 1 5 10 15 Phe Thr Gln Lys 20 <210> 1102 <211> 20 <212> PRT <213> Homo sapiens <400> 1102 Gly Phe Ser Pro Lys Asp Val Leu Val Arg Trp Leu Gln Gly Ser Gln 1 5 10 15 Glu Leu Pro Arg 20 <210> 1103 <211> 25 <212> PRT <213> Homo sapiens <400> 1103 His Tyr Thr Asn Pro Ser Gln Asp Val Thr Val Pro Cys Pro Val Pro 1 5 10 15 Pro Pro Pro Pro Cys Cys His Pro Arg 20 25 <210> 1104 <211> 21 <212> PRT <213> Homo sapiens <400> 1104 Lys Gly Asp Thr Phe Ser Cys Met Val Gly His Glu Ala Leu Pro Leu 1 5 10 15 Ala Phe Thr Gln Lys 20 <210> 1105 <211> 30 <212> PRT <213> Homo sapiens <400> 1105 Asn Phe Pro Pro Ser Gln Asp Ala Ser Gly Asp Leu Tyr Thr Thr Ser 1 5 10 15 Ser Gln Leu Thr Leu Pro Ala Thr Gln Cys Pro Asp Gly Lys 20 25 30 <210> 1106 <211> 17 <212> PRT <213> Homo sapiens <400> 1106 Gln Glu Pro Ser Gln Gly Thr Thr Thr Phe Ala Val Thr Ser Ile Leu 1 5 10 15 Arg <210> 1107 <211> 9 <212> PRT <213> Homo sapiens <400> 1107 Ser Ala Val Gln Gly Pro Pro Glu Arg 1 5 <210> 1108 <211> 32 <212> PRT <213> Homo sapiens <400> 1108 Ser Gly Asn Thr Phe Arg Pro Glu Val His Leu Leu Pro Pro Pro Ser 1 5 10 15 Glu Glu Leu Ala Leu Asn Glu Leu Val Thr Leu Thr Cys Leu Ala Arg 20 25 30 <210> 1109 <211> 7 <212> PRT <213> Homo sapiens <400> 1109 Ser Val Thr Cys His Val Lys 1 5 <210> 1110 <211> 10 <212> PRT <213> Homo sapiens <400> 1110 Gly Phe Ser Pro Lys Asp Val Leu Val Arg 1 5 10 <210> 1111 <211> 13 <212> PRT <213> Homo sapiens <400> 1111 Ala Gly Lys Gly Met His Gly Gly Val Pro Gly Gly Lys 1 5 10 <210> 1112 <211> 10 <212> PRT <213> Homo sapiens <400> 1112 Gly Met His Gly Gly Val Pro Gly Gly Lys 1 5 10 <210> 1113 <211> 7 <212> PRT <213> Homo sapiens <400> 1113 Gln Glu Leu Asn Pro Leu Lys 1 5 <210> 1114 <211> 10 <212> PRT <213> Homo sapiens <400> 1114 Gln Phe Ile Glu Ser Glu Cys Ile Pro Arg 1 5 10 <210> 1115 <211> 85 <212> PRT <213> Homo sapiens <400> 1115 Pro Ala Gln Glu Ala Gly Thr Ser Lys Pro Asn Glu Glu Ile Ser Gly 1 5 10 15 Pro Ala Glu Pro Ala Ser Pro Pro Glu Thr Thr Thr Thr Ala Gln Glu 20 25 30 Thr Ser Ala Ala Ala Val Gln Gly Thr Ala Lys Val Thr Ser Ser Arg 35 40 45 Gln Glu Leu Asn Pro Leu Lys Gln Ala Leu Ala Lys Ala Gly Lys Gly 50 55 60 Met His Gly Gly Val Pro Gly Gly Lys Gln Phe Ile Glu Ser Glu Cys 65 70 75 80 Ile Pro Arg Trp Lys 85 <210> 1116 <211> 21 <212> PRT <213> Homo sapiens <400> 1116 Val Phe Ser Asn Gly Ala Asp Leu Ser Gly Val Thr Glu Glu Ala Pro 1 5 10 15 Leu Lys Leu Ser Lys 20 <210> 1117 <211> 7 <212> PRT <213> Homo sapiens <400> 1117 Ser Pro Leu Phe Met Gly Lys 1 5 <210> 1118 <211> 22 <212> PRT <213> Homo sapiens <400> 1118 Gly Phe Tyr Pro Ser Asp Ile Ser Val Glu Trp Glu Ser Asn Gly Gln 1 5 10 15 Pro Glu Asn Asn Tyr Lys 20 <210> 1119 <211> 11 <212> PRT <213> Homo sapiens <400> 1119 Asp Leu Ala Thr Val Tyr Val Asp Val Leu Lys 1 5 10 <210> 1120 <211> 15 <212> PRT <213> Homo sapiens <400> 1120 Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys 1 5 10 15 <210> 1121 <211> 8 <212> PRT <213> Homo sapiens <400> 1121 Ser Glu Gln Phe Ile Asn Leu Arg 1 5 <210> 1122 <211> 8 <212> PRT <213> Homo sapiens <400> 1122 Leu Pro Ala Ser Phe Asp Ala Arg 1 5 <210> 1123 <211> 17 <212> PRT <213> Homo sapiens <400> 1123 Thr Thr Ile Glu Lys Pro Val Trp Leu Gly Phe Leu Gly Pro Ile Ile 1 5 10 15 Lys <210> 1124 <211> 11 <212> PRT <213> Homo sapiens <400> 1124 Asn Ser Lys Ile Glu Ile Ser Glu Leu Asn Arg 1 5 10 <210> 1125 <211> 16 <212> PRT <213> Homo sapiens <400> 1125 Ile Pro Glu Pro Gly Cys Thr Lys Val Pro Glu Pro Gly Cys Thr Lys 1 5 10 15 <210> 1126 <211> 23 <212> PRT <213> Homo sapiens <400> 1126 Glu Glu Pro Trp Val Asp Pro Asn Ser Pro Val Leu Leu Glu Asp Pro 1 5 10 15 Val Leu Cys Ala Leu Ala Lys 20 <210> 1127 <211> 11 <212> PRT <213> Homo sapiens <400> 1127 Val Ala Phe Thr Gly Ser Thr Glu Val Gly Lys 1 5 10 <210> 1128 <211> 24 <212> PRT <213> Homo sapiens <400> 1128 Asp Ala Ser Gly Val Thr Phe Thr Trp Thr Pro Ser Ser Gly Lys Ser 1 5 10 15 Ala Val Gln Gly Pro Pro Glu Arg 20 <210> 1129 <211> 732 <212> PRT <213> Homo sapiens <400> 1129 Met Pro Glu Glu Thr Gln Thr Gln Asp Gln Pro Met Glu Glu Glu Glu 1 5 10 15 Val Glu Thr Phe Ala Phe Gln Ala Glu Ile Ala Gln Leu Met Ser Leu 20 25 30 Ile Ile Asn Thr Phe Tyr Ser Asn Lys Glu Ile Phe Leu Arg Glu Leu 35 40 45 Ile Ser Asn Ser Ser Asp Ala Leu Asp Lys Ile Arg Tyr Glu Ser Leu 50 55 60 Thr Asp Pro Ser Lys Leu Asp Ser Gly Lys Glu Leu His Ile Asn Leu 65 70 75 80 Ile Pro Asn Lys Gln Asp Arg Thr Leu Thr Ile Val Asp Thr Gly Ile 85 90 95 Gly Met Thr Lys Ala Asp Leu Ile Asn Asn Leu Gly Thr Ile Ala Lys 100 105 110 Ser Gly Thr Lys Ala Phe Met Glu Ala Leu Gln Ala Gly Ala Asp Ile 115 120 125 Ser Met Ile Gly Gln Phe Gly Val Gly Phe Tyr Ser Ala Tyr Leu Val 130 135 140 Ala Glu Lys Val Thr Val Ile Thr Lys His Asn Asp Asp Glu Gln Tyr 145 150 155 160 Ala Trp Glu Ser Ser Ala Gly Gly Ser Phe Thr Val Arg Thr Asp Thr 165 170 175 Gly Glu Pro Met Gly Arg Gly Thr Lys Val Ile Leu His Leu Lys Glu 180 185 190 Asp Gln Thr Glu Tyr Leu Glu Glu Arg Arg Ile Lys Glu Ile Val Lys 195 200 205 Lys His Ser Gln Phe Ile Gly Tyr Pro Ile Thr Leu Phe Val Glu Lys 210 215 220 Glu Arg Asp Lys Glu Val Ser Asp Asp Glu Ala Glu Glu Lys Glu Asp 225 230 235 240 Lys Glu Glu Glu Lys Glu Lys Glu Glu Lys Glu Ser Glu Asp Lys Pro 245 250 255 Glu Ile Glu Asp Val Gly Ser Asp Glu Glu Glu Glu Lys Lys Asp Gly 260 265 270 Asp Lys Lys Lys Lys Lys Lys Ile Lys Glu Lys Tyr Ile Asp Gln Glu 275 280 285 Glu Leu Asn Lys Thr Lys Pro Ile Trp Thr Arg Asn Pro Asp Asp Ile 290 295 300 Thr Asn Glu Glu Tyr Gly Glu Phe Tyr Lys Ser Leu Thr Asn Asp Trp 305 310 315 320 Glu Asp His Leu Ala Val Lys His Phe Ser Val Glu Gly Gln Leu Glu 325 330 335 Phe Arg Ala Leu Leu Phe Val Pro Arg Arg Ala Pro Phe Asp Leu Phe 340 345 350 Glu Asn Arg Lys Lys Lys Asn Asn Ile Lys Leu Tyr Val Arg Arg Val 355 360 365 Phe Ile Met Asp Asn Cys Glu Glu Leu Ile Pro Glu Tyr Leu Asn Phe 370 375 380 Ile Arg Gly Val Val Asp Ser Glu Asp Leu Pro Leu Asn Ile Ser Arg 385 390 395 400 Glu Met Leu Gln Gln Ser Lys Ile Leu Lys Val Ile Arg Lys Asn Leu 405 410 415 Val Lys Lys Cys Leu Glu Leu Phe Thr Glu Leu Ala Glu Asp Lys Glu 420 425 430 Asn Tyr Lys Lys Phe Tyr Glu Gln Phe Ser Lys Asn Ile Lys Leu Gly 435 440 445 Ile His Glu Asp Ser Gln Asn Arg Lys Lys Leu Ser Glu Leu Leu Arg 450 455 460 Tyr Tyr Thr Ser Ala Ser Gly Asp Glu Met Val Ser Leu Lys Asp Tyr 465 470 475 480 Cys Thr Arg Met Lys Glu Asn Gln Lys His Ile Tyr Tyr Ile Thr Gly 485 490 495 Glu Thr Lys Asp Gln Val Ala Asn Ser Ala Phe Val Glu Arg Leu Arg 500 505 510 Lys His Gly Leu Glu Val Ile Tyr Met Ile Glu Pro Ile Asp Glu Tyr 515 520 525 Cys Val Gln Gln Leu Lys Glu Phe Glu Gly Lys Thr Leu Val Ser Val 530 535 540 Thr Lys Glu Gly Leu Glu Leu Pro Glu Asp Glu Glu Glu Lys Lys Lys 545 550 555 560 Gln Glu Glu Lys Lys Thr Lys Phe Glu Asn Leu Cys Lys Ile Met Lys 565 570 575 Asp Ile Leu Glu Lys Lys Val Glu Lys Val Val Val Ser Asn Arg Leu 580 585 590 Val Thr Ser Pro Cys Cys Ile Val Thr Ser Thr Tyr Gly Trp Thr Ala 595 600 605 Asn Met Glu Arg Ile Met Lys Ala Gln Ala Leu Arg Asp Asn Ser Thr 610 615 620 Met Gly Tyr Met Ala Ala Lys Lys His Leu Glu Ile Asn Pro Asp His 625 630 635 640 Ser Ile Ile Glu Thr Leu Arg Gln Lys Ala Glu Ala Asp Lys Asn Asp 645 650 655 Lys Ser Val Lys Asp Leu Val Ile Leu Leu Tyr Glu Thr Ala Leu Leu 660 665 670 Ser Ser Gly Phe Ser Leu Glu Asp Pro Gln Thr His Ala Asn Arg Ile 675 680 685 Tyr Arg Met Ile Lys Leu Gly Leu Gly Ile Asp Glu Asp Asp Pro Thr 690 695 700 Ala Asp Asp Thr Ser Ala Ala Val Thr Glu Glu Met Pro Pro Leu Glu 705 710 715 720 Gly Asp Asp Asp Thr Ser Arg Met Glu Glu Val Asp 725 730 <210> 1130 <211> 724 <212> PRT <213> Homo sapiens <400> 1130 Met Pro Glu Glu Val His His Gly Glu Glu Glu Val Glu Thr Phe Ala 1 5 10 15 Phe Gln Ala Glu Ile Ala Gln Leu Met Ser Leu Ile Ile Asn Thr Phe 20 25 30 Tyr Ser Asn Lys Glu Ile Phe Leu Arg Glu Leu Ile Ser Asn Ala Ser 35 40 45 Asp Ala Leu Asp Lys Ile Arg Tyr Glu Ser Leu Thr Asp Pro Ser Lys 50 55 60 Leu Asp Ser Gly Lys Glu Leu Lys Ile Asp Ile Ile Pro Asn Pro Gln 65 70 75 80 Glu Arg Thr Leu Thr Leu Val Asp Thr Gly Ile Gly Met Thr Lys Ala 85 90 95 Asp Leu Ile Asn Asn Leu Gly Thr Ile Ala Lys Ser Gly Thr Lys Ala 100 105 110 Phe Met Glu Ala Leu Gln Ala Gly Ala Asp Ile Ser Met Ile Gly Gln 115 120 125 Phe Gly Val Gly Phe Tyr Ser Ala Tyr Leu Val Ala Glu Lys Val Val 130 135 140 Val Ile Thr Lys His Asn Asp Asp Glu Gln Tyr Ala Trp Glu Ser Ser 145 150 155 160 Ala Gly Gly Ser Phe Thr Val Arg Ala Asp His Gly Glu Pro Ile Gly 165 170 175 Arg Gly Thr Lys Val Ile Leu His Leu Lys Glu Asp Gln Thr Glu Tyr 180 185 190 Leu Glu Glu Arg Arg Val Lys Glu Val Val Lys Lys His Ser Gln Phe 195 200 205 Ile Gly Tyr Pro Ile Thr Leu Tyr Leu Glu Lys Glu Arg Glu Lys Glu 210 215 220 Ile Ser Asp Asp Glu Ala Glu Glu Glu Lys Gly Glu Lys Glu Glu Glu 225 230 235 240 Asp Lys Asp Asp Glu Glu Lys Pro Lys Ile Glu Asp Val Gly Ser Asp 245 250 255 Glu Glu Asp Asp Ser Gly Lys Asp Lys Lys Lys Lys Thr Lys Lys Ile 260 265 270 Lys Glu Lys Tyr Ile Asp Gln Glu Glu Leu Asn Lys Thr Lys Pro Ile 275 280 285 Trp Thr Arg Asn Pro Asp Asp Ile Thr Gln Glu Glu Tyr Gly Glu Phe 290 295 300 Tyr Lys Ser Leu Thr Asn Asp Trp Glu Asp His Leu Ala Val Lys His 305 310 315 320 Phe Ser Val Glu Gly Gln Leu Glu Phe Arg Ala Leu Leu Phe Ile Pro 325 330 335 Arg Arg Ala Pro Phe Asp Leu Phe Glu Asn Lys Lys Lys Lys Asn Asn 340 345 350 Ile Lys Leu Tyr Val Arg Arg Val Phe Ile Met Asp Ser Cys Asp Glu 355 360 365 Leu Ile Pro Glu Tyr Leu Asn Phe Ile Arg Gly Val Val Asp Ser Glu 370 375 380 Asp Leu Pro Leu Asn Ile Ser Arg Glu Met Leu Gln Gln Ser Lys Ile 385 390 395 400 Leu Lys Val Ile Arg Lys Asn Ile Val Lys Lys Cys Leu Glu Leu Phe 405 410 415 Ser Glu Leu Ala Glu Asp Lys Glu Asn Tyr Lys Lys Phe Tyr Glu Ala 420 425 430 Phe Ser Lys Asn Leu Lys Leu Gly Ile His Glu Asp Ser Thr Asn Arg 435 440 445 Arg Arg Leu Ser Glu Leu Leu Arg Tyr His Thr Ser Gln Ser Gly Asp 450 455 460 Glu Met Thr Ser Leu Ser Glu Tyr Val Ser Arg Met Lys Glu Thr Gln 465 470 475 480 Lys Ser Ile Tyr Tyr Ile Thr Gly Glu Ser Lys Glu Gln Val Ala Asn 485 490 495 Ser Ala Phe Val Glu Arg Val Arg Lys Arg Gly Phe Glu Val Val Tyr 500 505 510 Met Thr Glu Pro Ile Asp Glu Tyr Cys Val Gln Gln Leu Lys Glu Phe 515 520 525 Asp Gly Lys Ser Leu Val Ser Val Thr Lys Glu Gly Leu Glu Leu Pro 530 535 540 Glu Asp Glu Glu Glu Lys Lys Lys Met Glu Glu Ser Lys Ala Lys Phe 545 550 555 560 Glu Asn Leu Cys Lys Leu Met Lys Glu Ile Leu Asp Lys Lys Val Glu 565 570 575 Lys Val Thr Ile Ser Asn Arg Leu Val Ser Ser Pro Cys Cys Ile Val 580 585 590 Thr Ser Thr Tyr Gly Trp Thr Ala Asn Met Glu Arg Ile Met Lys Ala 595 600 605 Gln Ala Leu Arg Asp Asn Ser Thr Met Gly Tyr Met Met Ala Lys Lys 610 615 620 His Leu Glu Ile Asn Pro Asp His Pro Ile Val Glu Thr Leu Arg Gln 625 630 635 640 Lys Ala Glu Ala Asp Lys Asn Asp Lys Ala Val Lys Asp Leu Val Val 645 650 655 Leu Leu Phe Glu Thr Ala Leu Leu Ser Ser Gly Phe Ser Leu Glu Asp 660 665 670 Pro Gln Thr His Ser Asn Arg Ile Tyr Arg Met Ile Lys Leu Gly Leu 675 680 685 Gly Ile Asp Glu Asp Glu Val Ala Ala Glu Glu Pro Asn Ala Ala Val 690 695 700 Pro Asp Glu Ile Pro Pro Leu Glu Gly Asp Glu Asp Ala Ser Arg Met 705 710 715 720 Glu Glu Val Asp <210> 1131 <211> 9 <212> PRT <213> Homo sapiens <400> 1131 Ala Pro Phe Asp Leu Phe Glu Asn Arg 1 5 <210> 1132 <211> 17 <212> PRT <213> Homo sapiens <400> 1132 Cys Leu Glu Leu Phe Thr Glu Leu Ala Glu Asp Lys Glu Asn Tyr Lys 1 5 10 15 Lys <210> 1133 <211> 27 <212> PRT <213> Homo sapiens <400> 1133 Asp Leu Val Ile Leu Leu Tyr Glu Thr Ala Leu Leu Ser Ser Gly Phe 1 5 10 15 Ser Leu Glu Asp Pro Gln Thr His Ala Asn Arg 20 25 <210> 1134 <211> 11 <212> PRT <213> Homo sapiens <400> 1134 Asp Gln Val Ala Asn Ser Ala Phe Val Glu Arg 1 5 10 <210> 1135 <211> 12 <212> PRT <213> Homo sapiens <400> 1135 Glu Leu Ile Ser Asn Ser Ser Asp Ala Leu Asp Lys 1 5 10 <210> 1136 <211> 14 <212> PRT <213> Homo sapiens <400> 1136 Gly Val Val Asp Ser Glu Asp Leu Pro Leu Asn Ile Ser Arg 1 5 10 <210> 1137 <211> 10 <212> PRT <213> Homo sapiens <400> 1137 His Ile Tyr Tyr Ile Thr Gly Glu Thr Lys 1 5 10 <210> 1138 <211> 15 <212> PRT <213> Homo sapiens <400> 1138 His Leu Glu Ile Asn Pro Asp His Ser Ile Ile Glu Thr Leu Arg 1 5 10 15 <210> 1139 <211> 15 <212> PRT <213> Homo sapiens <400> 1139 His Ser Gln Phe Ile Gly Tyr Pro Ile Thr Leu Phe Val Glu Lys 1 5 10 15 <210> 1140 <211> 10 <212> PRT <213> Homo sapiens <400> 1140 Leu Gly Ile His Glu Asp Ser Gln Asn Arg 1 5 10 <210> 1141 <211> 15 <212> PRT <213> Homo sapiens <400> 1141 Asn Pro Asp Asp Ile Thr Asn Glu Glu Tyr Gly Glu Phe Tyr Lys 1 5 10 15 <210> 1142 <211> 13 <212> PRT <213> Homo sapiens <400> 1142 Ser Leu Thr Asn Asp Trp Glu Asp His Leu Ala Val Lys 1 5 10 <210> 1143 <211> 16 <212> PRT <213> Homo sapiens <400> 1143 Val Ile Leu His Leu Lys Glu Asp Gln Thr Glu Tyr Leu Glu Glu Arg 1 5 10 15 <210> 1144 <211> 9 <212> PRT <213> Homo sapiens <400> 1144 Tyr Ile Asp Gln Glu Glu Leu Asn Lys 1 5 <210> 1145 <211> 11 <212> PRT <213> Homo sapiens <400> 1145 Glu Gln Val Ala Asn Ser Ala Phe Val Glu Arg 1 5 10 <210> 1146 <211> 14 <212> PRT <213> Homo sapiens <400> 1146 Gly Val Val Asp Ser Glu Asp Leu Pro Leu Asn Ile Ser Arg 1 5 10 <210> 1147 <211> 15 <212> PRT <213> Homo sapiens <400> 1147 Asn Pro Asp Asp Ile Thr Gln Glu Glu Tyr Gly Glu Phe Tyr Lys 1 5 10 15 <210> 1148 <211> 10 <212> PRT <213> Homo sapiens <400> 1148 Ser Ile Tyr Tyr Ile Thr Gly Glu Ser Lys 1 5 10 <210> 1149 <211> 13 <212> PRT <213> Homo sapiens <400> 1149 Ser Leu Thr Asn Asp Trp Glu Asp His Leu Ala Val Lys 1 5 10 <210> 1150 <211> 16 <212> PRT <213> Homo sapiens <400> 1150 Val Ile Leu His Leu Lys Glu Asp Gln Thr Glu Tyr Leu Glu Glu Arg 1 5 10 15 <210> 1151 <211> 9 <212> PRT <213> Homo sapiens <400> 1151 Tyr Ile Asp Gln Glu Glu Leu Asn Lys 1 5 <210> 1152 <211> 17 <212> PRT <213> Homo sapiens <400> 1152 Ala Asp Gly Ser Pro Val Lys Ala Gly Val Glu Thr Thr Lys Pro Ser 1 5 10 15 Lys <210> 1153 <211> 10 <212> PRT <213> Homo sapiens <400> 1153 Ala Gly Val Glu Thr Thr Lys Pro Ser Lys 1 5 10 <210> 1154 <211> 19 <212> PRT <213> Homo sapiens <400> 1154 Ala Asn Pro Thr Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln 1 5 10 15 Ala Asn Lys <210> 1155 <211> 20 <212> PRT <213> Homo sapiens <400> 1155 Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro 1 5 10 15 Glu Gln Trp Lys 20 <210> 1156 <211> 13 <212> PRT <213> Homo sapiens <400> 1156 Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Lys 1 5 10 <210> 1157 <211> 18 <212> PRT <213> Homo sapiens <400> 1157 Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val 1 5 10 15 Glu Lys <210> 1158 <211> 15 <212> PRT <213> Homo sapiens <400> 1158 Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys 1 5 10 15 <210> 1159 <211> 23 <212> PRT <213> Homo sapiens <400> 1159 Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr 1 5 10 15 Val Ala Pro Thr Glu Cys Ser 20 <210> 1160 <211> 8 <212> PRT <213> Homo sapiens <400> 1160 Thr Val Ala Pro Thr Glu Cys Ser 1 5 <210> 1161 <211> 13 <212> PRT <213> Homo sapiens <400> 1161 Ile Tyr Gly Asn Gln Asp Thr Ser Ser Gln Leu Lys Lys 1 5 10 <210> 1162 <211> 11 <212> PRT <213> Homo sapiens <400> 1162 Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 1 5 10

Claims (23)

  1. 대상체가 암을 갖는지 여부를 결정하기 위한 정보를 제공하는 방법으로서,
    대상체로부터 분리된 눈물 샘플을 제공하는 단계; 표 1에 제공된 마커 목록으로부터의 2 이상의 마커의 샘플 내 수준을 검출하는 단계; 및 마커의 수준이 암이 없는 대조군 샘플 내 수준과 비교하여 변화하였다면, 대상체가 암을 갖거나 또는 암을 가질 가능성이 있는 것으로 나타내는 단계를 포함하고,
    상기 2 이상의 마커는 S100A9 및 LG3BP를 포함하고, S100A9의 수준은 증가되고, LG3BP의 수준은 감소되는 것인, 방법.
  2. 제1항에 있어서, 암이 유방암인 것인, 방법.
  3. 제1항에 있어서, 대상체가 인간인 것인, 방법.
  4. 제1항에 있어서, LG3BP 마커가 대조군 샘플 내 마커의 수준과 비교하여 적어도 1.5배, 2배 또는 4배 이상 감소된 것인, 방법.
  5. 제1항에 있어서, S100A9 마커가 대조군 샘플 내 마커의 수준과 비교하여 적어도 1.5배, 2배 또는 4배 이상 증가된 것인, 방법.
  6. 제1항에 있어서, 상기 방법은 표 1에 제공된 마커 목록으로부터의 3번째 마커의 수준을 검출하는 단계를 포함하고,
    암이 없는 대조군 샘플 내 수준과 비교하여 샘플 내 3번째 마커의 수준의 변화는, 대상체가 유방암을 갖거나 또는 유방암을 가질 가능성이 있는 것을 나타내고, 3번째 마커는 S100A8을 포함하고, S100A8의 수준은 증가되는 것인, 방법.
  7. 제1항에 있어서, 마커 수준이 액체 크로마토그래피-질량 분광법 (LC-MS)에 의해 검출되는 것인, 방법.
  8. 제1항에 있어서, 마커 수준이 항체 기반 검출 방법에 의해 검출되는 것인, 방법.
  9. 제1항에 있어서, 마커 수준이 다중 단백질 검출 방법에 의해 검출되는 것인, 방법.
  10. 제1항에 있어서, 마커 수준이 mRNA 검출 방법에 의해 검출되는 것인, 방법.
  11. 제1항에 있어서, 대상체가 암을 갖는 것으로 의심되는 것인, 방법.
  12. 제1항에 있어서, 대상체는 암이 발병될 위험이 증가한 것인, 방법.
  13. 제2항에 있어서, 대상체가 암성인 것으로 의심되는 촉진성 종괴를 가지는 것인, 방법.
  14. 제1항에 있어서, 대상체의 유방 밀도가 카테고리 1, 카테고리 2, 카테고리 3 또는 카테고리 4인 것인, 방법.
  15. 제1항에 있어서, 암이 유방암의 한 병기로 검출되는 것인, 방법.
  16. 수집튜브 및 프로테아제 억제제를 포함하는, 제1항 내지 제15항 중 어느 한 항의 방법을 수행하기 위한 키트.
  17. 제16항에 있어서, 1 이상의 마커에 결합할 수 있는 항체를 추가로 포함하는 것인, 키트.
  18. 제16항에 있어서, 1 이상의 마커를 증폭시킬 수 있는 프라이머 쌍을 추가로 포함하는 것인, 키트.
  19. 면역검정 시스템으로서,
    (a) 인간 대상체로부터 분리된 눈물 분비 샘플로서, 대상체가 유방암을 갖는 것으로 의심되거나 또는 암성인 것으로 의심되는 촉진성 종괴를 갖고, 눈물 분비 샘플이 S100A9 및 LG3BP를 포함하는 2 이상의 단백질 마커를 포함하는 것인, 눈물 분비 샘플; 및
    (b) 검출가능한 신호의 발생에 기초하여 정량화될 수 있는 반응을 생성하도록 (a)의 2 이상의 단백질 마커에 특이적인 결합 상호작용을 제공하는 결합제 및 시약을 포함하고,
    암이 아닌 대조군 샘플에 비해 S100A9의 수준은 증가되고, LG3BP의 수준은 감소되는 것인, 면역검정 시스템.
  20. 제19항에 있어서, 눈물 분비 샘플은 S100A8을 포함하는 3번째 단백질 마커를 포함하고, 결합제는 S100A8 단백질 마커에 특이적으로 결합하는 항체를 포함하고, S100A8의 수준은 암이 아닌 대조군 샘플에 비해 증가되는, 면역검정 시스템.
  21. 제19항 또는 제20항에 있어서, 눈물 분비 샘플은 안구 세액 샘플인, 면역검정 시스템.
  22. 제19항 또는 제20항에 있어서, 대상체의 유방 밀도가 카테고리 1, 카테고리 2, 카테고리 3 또는 카테고리 4인 것인, 면역검정 시스템.
  23. 표 1에 제공된 마커 목록으로부터의 2 이상의 마커를 포함하는, 대상체가 암을 갖는지 여부를 결정하기 위한 마커 조성물로서, 상기 마커는 눈물 샘플 유래이고, 상기 2 이상의 마커는 S100A9 및 LG3BP를 포함하는 것인, 마커 조성물.
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Citations (2)

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Publication number Priority date Publication date Assignee Title
US20120183555A1 (en) 2007-07-26 2012-07-19 Temple University Of The Commonwealth System Of Higher Education Serum markers associated with early and other stages of breast cancer
US20160003786A1 (en) 2014-05-09 2016-01-07 Ascendant Diagnostics, LLC Methods Of Detecting Cancer

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Publication number Priority date Publication date Assignee Title
US20120183555A1 (en) 2007-07-26 2012-07-19 Temple University Of The Commonwealth System Of Higher Education Serum markers associated with early and other stages of breast cancer
US20160003786A1 (en) 2014-05-09 2016-01-07 Ascendant Diagnostics, LLC Methods Of Detecting Cancer

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Title
비특허문헌 1(논문,ONCOLOGY REPORTS 28, 2012)
비특허문헌 2(논문, CANCER GENOMICS PROTEOMICS, 2009)

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