KR20220142472A - 감염을 치료하거나 또는 감염의 진행을 제한하기 위한 폴리펩타이드, 조성물 및 그 용도 - Google Patents

감염을 치료하거나 또는 감염의 진행을 제한하기 위한 폴리펩타이드, 조성물 및 그 용도 Download PDF

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KR20220142472A
KR20220142472A KR1020227031351A KR20227031351A KR20220142472A KR 20220142472 A KR20220142472 A KR 20220142472A KR 1020227031351 A KR1020227031351 A KR 1020227031351A KR 20227031351 A KR20227031351 A KR 20227031351A KR 20220142472 A KR20220142472 A KR 20220142472A
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넬 피 킹
데이비드 비슬러
칼 월키
알렉산드라 씨 왈스
징 양 왕
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유니버시티 오브 워싱턴
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Abstract

본 발명은 서열번호 1-84, 138-146 및 167-184로 이루어진 군으로부터 선택되는 아미노산 서열에 대해 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99% 또는 적어도 100% 동일한 아미노산 서열을 포함하는 폴리펩타이드, 이의 나노입자, 관련 나노입자 조성물 및 감염을 치료 또는 감염의 진행을 제한하기 위한 용도를 개시한다.

Description

감염을 치료하거나 또는 감염의 진행을 제한하기 위한 폴리펩타이드, 조성물 및 그 용도
교차 참조
본 출원은 2020년 2월 14일자 미국 가출원번호 62/977,036, 2020년 6월 30일자 63/046,159, 및 2020년 8월 11일자 63/064,235에 대해 우선권을 주장하며, 이들은 각각 그 전체가 원용에 의해 본 명세서에 포함된다.
연방 자금 지원에 관한 진술
본 발명은 국립 보건원에서 부여한 승인 번호 HHSN272201700059C 및 R01 GM120553 하에 정부 지원으로 이루어졌다. 정부가 본 발명에 대해 일정한 권리를 가진다.
서열목록에 관한 진술:
서열목록은 컴퓨터 판독가능한 형태로 본 출원시 전자 제출을 통해 제출되며, 그 전체가 원용에 의해 본 출원에 통합된다. 서열목록은 2021년 2월 11일에 생성된 파일명 "20-1008-PCT_SeqList_ST25.txt"에 수록되며, 파일 크기는 1077 kb이다.
최근 중국 우한에서 기존에 알려지지 않은 바이러스의 출현은 현재 진행 중인 COVID-19 대유행을 이끌었으며, 2020년 8월 6일자 기준으로 감염 18,700,000건 이상 및 사망 700,000건 이상이 발생하였다. 신속한 바이러스 단리 및 서열 분석을 통해, 2020년 1월까지, 새롭게 등장한 인수공통 병원체가 SARS-CoV에 매우 가까운 코로나바이러스인 것으로 밝혀졌으며, 그래서 SARS-CoV-2로 명명되었다. SARS-CoV-2는 리놀로푸스 아피니스 (Rhinolophus affinis)에서 연관성이 높은 RaTG13 바이러스의 단리 및 리놀로푸스 말라야누스 (Rhinolophus malayanus)의 메타유전체학 분석에서 RmYN02 게놈 서열의 동정을 토대로 박쥐에서 기원한 것으로 보인다.
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일 측면에서, 본 발명은 서열번호 1-84, 138-146 및 167-184로 이루어진 군으로부터 선택되는 아미노산 서열에 대해 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99% 또는 적어도 100% 동일한 아미노산 서열을 포함하는 폴리펩타이드로서, X1이 생략되거나 또는 아미노산 링커이고, 괄호 안 잔기는 선택적으로, 존재할 수 있거나 또는 선택 잔기들 중 일부 또는 전부 생략될 수 있는, 폴리펩타이드를 제공한다. 다양한 구체적인 구현예들에서, 폴리펩타이드는 서열번호 1-12 및 142-151로 이루어진 군으로부터 선택되는 아미노산 서열을 포함하거나, 서열번호 1-8로 이루어진 군으로부터 선택되는 아미노산 서열을 포함하거나, 또는 서열번호 1 또는 5로 이루어진 군으로부터 선택되는 아미노산 서열을 포함한다. 다른 구현예에서, 본 발명은 이러한 폴리펩타이드를 복수개 포함하는 나노입자를 제공한다.
다른 측면에서, 본 발명은 나노입자를 제공하되, 나노입자는
(a) 각각의 제1 어셈블리가 동일한 복수의 제1 단백질을 포함하는, 복수의 제1 어셈블리; 및
(b) 각각의 제2 어셈블리가 동일한 복수의 제2 단백질을 포함하는, 복수의 제2 어셈블리를 포함하고,
제1 단백질의 아미노산 서열은 제2 단백질의 서열과 상이하고; 복수의 제1 어셈블리는 복수의 제2 어셈블리와 비-공유적으로 상호작용해 나노입자를 형성하고; 나노입자는 그 표면에 제2 단백질 하나 이상에 존재하는 SARS-CoV-2 항원 또는 이의 변이체 또는 상동체의 면역원성 부분을 표면에 나열하는, 나노입자를 제공한다. 일 구현예에서, 제2 단백질은 서열번호 85-124 또는 185-193에 대해 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99% 또는 적어도 100% 동일한 아미노산 서열로 이루어진 또는 서열번호 85-88로 이루어진 군으로부터 선택되는 아미노산 서열을 포함하되, 하나 이상의 제2 단백질에서 X1은 SARS-CoV-2 항원 또는 이의 변이체 또는 상동체의 면역원성 부분을 포함하고, X2는 생략되거나 또는 아미노산 링커이고, 괄호 안 잔기들은 선택적이다. 다른 구현예에서, 제2 단백질들 중 적어도 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% 또는 100%에서 X1은 SARS-CoV-2로부터 유래한 스파이크 (S) 단백질 세포외 도메인 (ECD) 아미노산 서열, S1 서브유닛 아미노산 서열, S2 서브유닛 아미노산 서열, S1 수용체 결합 도메인 (RBD) 아미노산 서열, 및/또는 N-말단 도메인 (NTD) 아미노산 서열 또는 이의 변이체 또는 상동체에 대해 적어도 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100%의 아미노산 서열 동일성을 가진 아미노산 서열을 포함한다. 추가적인 구현예에서, 제2 단백질들 중 적어도 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% 또는 100%는 X1이 서열번호 125-137로 이루어진 군으로부터 선택되는 아미노산 서열에 대해 적어도 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100%의 아미노산 서열 동일성을 가진 아미노산 서열을 포함한다. 추가적인 구현예에서, 제1 단백질은 서열번호 152-159로 이루어진 군으로부터 선택되는 아미노산 서열에 대해 적어도 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100% 동일한 아미노산 서열을 포함하며, 괄호 안 서열은 선택적으로, 존재할 수 있거나 또는 선택 잔기들 중 일부 또는 전부 생략될 수 있다.
다양한 다른 측면들에서, 본 발명은 본원에 개시된 복수의 나노입자를 포함하는 조성물, 본원에 개시된 폴리펩타이드를 암호화하는 핵산 분자, 예를 들어 mRNA, 적절한 조절 서열에 작동가능하게 연결된 본원에 개시된 핵산 분자를 포함하는 발현 벡터, 본원에 개시된 폴리펩타이드, 나노입자, 조성물, 핵산 및/또는 발현 벡터를 포함하는 세포, 및 본원에 개시된 폴리펩타이드, 나노입자, 조성물, 핵산, 발현 벡터 및/또는 세포를 포함하는 약학적 조성물, 키트 및 백신을 제공한다.
다른 측면에서, 본 발명은 본원에 개시된 폴리펩타이드, 나노입자, 조성물, 핵산, 약학적 조성물 또는 백신을 감염을 치료하거나 또는 감염의 진행을 제한하는데 효과적인 양으로 필요한 개체에 투여하는 것을 포함하는, SARS-CoV-2 감염을 치료 또는 진행을 제한하기 위한 방법을 제공한다.
도 1 (A-H). SARS-CoV-2 RBD 나노입자 면역원의 설계, 시험관내 조립 및 특징 규명. (A) 융합되기 전 형태로서 SARS-CoV-2 S-2P 삼량체의 분자 표면 도시 (PDB 6VYB). 각 프로모터는 색상으로 구분되고, N-연결된 글리칸은 진한 청색으로 표시된다 (N343 위치에서 글리칸은 PDB 6WPS를 기반으로 모델링하고, 수용체-결합 모티프 (RBM)는 PDB 6M0J로부터 모델링함). 하나의 개방된 RBD는 박스로 표시한다. (B) 331 및 343번 위치에 N-연결된 글리칸을 가진 SARS-CoV-2 S RBD의 분자 표면 도시. ACE2 수용체-결합 부위 또는 RBM은 검정 윤곽선으로 표시한다. (C) 삼량체 RBD-I53-50A (RBD는 연청색이고, I53-50A는 연회색임) 및 오량체 I53-50B (오렌지색) 구성성분들의 구조 모델. 시험관내 혼합시, 삼량체 구성성분 20개와 오량체 구성성분 12개가 조립되어 정20면체 대칭성을 가진 나노입자 면역원이 형성된다. 각 나노입자는 RBD 카피를 60개 나열한다. (D) RBD-12GS-I53-50 나노입자 면역원의 구조 모델. 나열된 RBD 항원 및 12-잔기 링커는 한가지 배향성으로 도시되지만, 이들 영역들은 I53-50 나노입자 스캐폴드에 대해 가요성일 것으로 예상된다. (E) 비변형 I53-50 나노입자와 비교한 RBD-8GS-I53-50 나노입자, RBD-12GS-I53-50 나노입자 및 RBD-16GS-I53-50 나노입자의 동적 광 산란 (DLS). (F) 음성 염색된 RBD-8GS-I53-50 나노입자, RBD-12GS-I53-50 나노입자 및 RBD-16GS-I53-50 나노입자에 대한 대표적인 전자 현미경 사진. 샘플은 냉동/해동 사이클 1회 수행 후 사진 촬영하였다. 기준자, 100 nm. (G) 나비 그래피로 도시된, 단량체 RBD 대비 삼량체 RBD-8GS-I53-50A 구성성분의 수소/중수소-교환 질량 분광 측정은 공지된 중화 Ab에 의해 인지되는 에피토프에서를 비롯해 RBD 형태의 보존성을 검증해준다. 그래프에서, 수평 서열 축에 따른 각 점은 중수소 흡수가 3초부터 20시간까지 모니터링한 펩타이드를 나타낸다. 나비 그래프에 표시된 오차 막대는 2세트 실험의 표준 편차를 나타낸다. 하단 차이 도표는 단량체 RBD와 RBD-8GS-I53-50A가 RBD에서 국소 구조적 순서가 사실상 동일함을 보여준다. (H) 단백질 샘플 5종, 즉 단량체 RBD, S-2P 삼량체, RBD-8GS 삼량체-I53-50A 구성성분, RBD-12GS-I53-50A 삼량체 구성성분, 및 RBD-16GS-I53-50A 삼량체 구성성분에서 N-연결된 당화 부위 N331 및 N343에 존재하는 글리칸 집단을 요약 개시한 원형 도표. 이들 2가지 부위에서 대부분의 복합 글리칸들은 푸코실화되었으며; 탈푸코실화된 글리칸 (afucosylated glycan)인 소수 집단은 점선으로 표시한다. 올리고, 올리고만노스.
도 2 (A-B). SARS-CoV-2 RBD-I53-50 나노입자 면역원의 항원 특징 규명. (A) RBD 항원이 50% 또는 100% 결합가 (valency)로 나열된 RBD-8GS-I53-50 나노입자, RBD-12GS-I53-50 나노입자 및 RBD-16GS-I53-50 나노입자에의, 고정된 mACE2-Fc, CR3022 mAb 및 S309 mAb 결합에 대한 생물층 간섭 측정. 각 실험에 기준으로서 단량체 SARS-CoV-2 RBD를 포함시켰다. (B) 결합 단계 종료 시점 무렵인 880 s에서의 결합 신호를 각 나노입자로부터 수득한 결합 신호를 비교하기 위해 패널 (A)에 각 실험에 대해 그래프로 도시한다.
도 3 (A-E). RBD 나노입자 면역원 및 S-2P 삼량체의 물리적 및 항원성 안정성. (A) 구아니딘 하이드로클로라이드에 의한 화학적 변성. 350/320 nm에서의 고유한 트립토판 형광 방출 비율을 이용해 단백질의 3차 구조를 모니터링하였다. 중대한 전이 (transition)는 음영 영역으로 표시한다. 독립적인 실험 3종 중 하나의 대표적인 데이터를 나타낸다. (B) 4주에 걸친 SDS-PAGE 및 nsEM 안정성 데이터 요약. SDS-PAGE에서 어떤 샘플에서도 검출가능한 변성은 확인되지 않았다. nsEM은 3일간 인큐베이션한 후 2-8℃에서, 그리고 4주 후 22-27℃에서 S-2P 삼량체가 실질적으로 언폴딩 상태임을 보여준다. N/A, 평가하지 않음. (C) 4주에 걸친 항원 데이터 요약. 항원은 다양한 온도에서 보관한 후 생물층 간섭 측정으로 mACE2-Fc (실선) 및 CR3022 mAb (점선)의 결합성을 분석하였다. 도시된 값은 결합 단계의 종료 시점 무렵에 대응되는 < -70℃ 샘플에 대해 표준화한 각 시점의 신호 진폭을 나타낸다. (D) 4주에 걸친 UV/vis 안정성 데이터 요약. 320/280 nm에서 흡광도 비율은 미립자 산란의 척도로서 표시된다. S-2P 삼량체 및 RBD-12GS-I53-50 나노입자에서만 임의의 산란 증가가 오직 주위 온도에서 나타났다. (E) RBD-12GS-I53-50 나노입자의 DLS는 단분산 종임을 나타내며, 모든 온도 및 시점에서 응집체는 검출가능하지 않았다. 패널 B-E의 데이터는 1회 수행한 4주간의 실시간 안정성 실험으로부터 수득한 것이다.
도 4 (A-D). RBD-I53-50 나노입자 면역원은 BALB/c 및 인간 면역 레퍼토리 마우스에서 강력한 항체 반응을 일으킨다. (A-B) BALB/c 마우스에서 ELISA에 의해 측정한 감작 후 (2주) (A) 및 부스트 후 (5주) (B) anti-S 결합 역가. 각 기호는 개별 동물을 나타내고, 각 군의 기하 평균은 수평선으로 표시한다. 점선은 분석의 검출 하한을 나타낸다. 8GS, RBD-8GS-I53-50; 12GS, RBD-12GS-I53-50; 16GS, RBD-16GS-I53-50; HCS, 인간 회복기 혈청. 삽입도는 실험 일정을 나타낸다. 면역화 실험을 2회 반복하였으며, 대표적인 데이터를 나타낸다. (C-D) 재배열되지 않은 인간 항체 가변부 및 불변부 생식계열 레퍼토리에 대해 형질전환된 Kymab Darwin™ 마우스에서, ELISA에 의해 측정하여 (A)에서와 같이 나타낸, 감작 후 (2주) (C) 및 부스트 후 (5주) (D) anti-S 결합 역가. 삽입도는 실험 일정을 나타낸다. 면역화 실험은 1회 수행하였다.
도 5 (A-H). RBD-I53-50 나노입자 면역원은 강력한 보호성 중화 항체 반응을 일으킨다. (A-B) 단량체 RBD, S-2P 삼량체 또는 RBD-I53-50 나노입자로 면역화한 마우스에서 감작 후 (A) 또는 부스트 후 (B) 혈청 슈도바이러스 중화 역가. 각각의 원은 개별 동물의 역수 IC50 (reciprocal IC50) 값을 나타낸다. 각 군의 기하 평균을 수평선으로 표시한다. 검출 한계는 회색 점선으로 나타낸다. 동물 실험을 2번 수행하였으며, 2번의 실험에서 수득한 대표적인 데이터를 나타낸다. (C-D) (A)에 기술된 바와 같이 면역화한 마우스에서의 감작 후 (C) 또는 부스트 후 (D) 혈청 생 바이러스 중화 역가. (E-F) (A)에 기술된 바와 같이 면역화한 Kymab Darwin™ 마우스에서의 감작 후 (E) 또는 부스트 후 (F) 혈청 슈도바이러스 중화 역가. 동물 실험은 1회 수행하였으며, 중화 분석은 적어도 2 세트로 수행하였다. (G-H) 부스트 후 7주 경과시, BALB/c 마우스 8마리/군에 SARS-CoV-2 MA를 기회 감염시켰다. 기회 감염 후 2일 경과시 폐 조직 (G) 및 비갑개 (H)에서 바이러스 역가를 분석하였다. 검출 한계는 회색 점선으로 표시된다.
도 6 (A-J). RBD 나노입자 백신은 마우스 및 비-인간 영장류에서 견고한 B 세포 반응 및 다중 에피토프를 표적화하는 항체를 유발한다. (A-B) 각 면역화 군에서 검출된 (A) RBD+ B 세포 (B220+CD3-CD138-) 및 (B) RBD+ GC 전구체와 B 세포 (CD38+/-GL7+)의 수. (C-D) (C) RBD+ GC 전구체 및 B 세포 (CD38+/-GL7+) 및 (D) IgD+, IgM+, 또는 클래스-스위칭된 (IgM-IgD-; swIg+) RBD+ GC 전구체 및 B 세포의 빈도. (A-D) 각 군별 실험 2종에서 N=6. 통계학적 유의성을 일원식 분산분석으로 결정하였으며, p-값이 <0.05인 임의 군에서 터키의 다중 비교 검정을 수행하였다. 유의성은 별표로 표시한다: * p < 0.05, **** p < 0.0001. (E) Kymab Darwin™ 마우스에서 부스트 후 (5주) 슈도바이러스 중화 역가 (도 5F)에 대한 S-2P ELISA 결합 역가 (도 4D)의 비율. 비율은 [마우스 5마리의 GMT (EC50)]:[마우스 5마리의 GMT (IC50)] 또는 검사한 모든 HCS의 EC50:IC50이다. 값이 낮을수록 정성적인 반응 (quality response)이 우수하다는 것을 의미한다. (F) BALB/c 마우스에서 부스트 후 (5주) 슈도바이러스 (도 5B) 또는 생 바이러스 (도 5D) 중화 역가에 대한 S-2P ELISA 결합 역가 (도 4B)의 비율. 비율은 [마우스 10마리의 GMT (EC50)]:[마우스 10마리의 GMT (IC50)] 또는 검사한 전체 HCS의 EC50:IC50이다. (G) 단량체 ACE2, CR3022 Fab 및 S309 Fab가 결합된 SARS-CoV-2 RBD. (H-J) 경쟁적인 BLI에 의한 백신-유발된 Ab 에피토프 특이성 결정. 다클론 NHP Fab의 연속 희석물을 BLI 팁 상에서 RBD와 예비 인큐베이션하였다. 다클론 Fab 농도는 각 희석 시점에 경쟁물질을 첨가하여 유지시켰다. 다클론 Fab의 1:3 연속 희석물을 진한 색에서 연한 색으로 나타내고, 진한 회색 선은 apo-RBD (경쟁 없음)에 경쟁물질을 로딩한 것을 나타낸다. (H) 200 nM ACE2, (I) 400 nM CR3022, 또는 (J) 20 nM S309를 이용한 경쟁.
도 7 (A-E). RBD 나노입자 면역원에 대한 추가적인 특징 규명. (A) RBD-I53-50 나노입자, 비-변형된 I53-50 나노입자 및 삼량체 RBD-I53-50A 구성성분들의 Superose™ 6 Increase 10/300 GL에서의 크기 배제 크로마토그래피. (B) 냉동/해동 사이클 수행 전 및 1회 수행 후 SEC-정제한 RBD-I53-50 나노입자의 환원 및 비-환원 조건 하 SDS-PAGE. (C) 냉동/해동 사이클 수행 전 및 사이클 1회 수행 후 RBD-I53-50 나노입자에 대한 동적 광 산란에서 각 샘플에 검출가능한 응집체가 없는 단분산 나노입자인 것으로 확인된다. (D) 히트맵으로 나타낸 수소/중수소-교환 질량 분광 측정은 RBD (PDB 6W41)에 대한 구조적 접근성 및 다이나믹스를 보여준다. 색상 코드는 중수소 흡수 수준을 나타낸다. 단량체 RBD 및 RBD-8GS-I53-50A는 구분할 수 없는 흡수 패턴을 보이며, 각 시점에 따라 단일 히트맵으로 나타낸다. (E) 상단, 막대 그래프는 단백질 샘플 5종, 단량체 RBD, S-2P 삼량체 및 RBD-8GS-I53-50A 삼량체 구성성분, RBD-12GS-I53-50A 삼량체 구성성분 및 RBD-16GS-I53-50A 삼량체 구성성분이 N-연결된 당화 부위 N331 및 N343의 글리칸 프로파일 측면에서 유사함을 보여준다. 하단, S-2P 삼량체에서 발견된, N331 및 N343 이외의 다른 N-연결된 당화 부위에서의 포괄적인 글리칸 프로파일링. 각 막대 그래프의 축은 0-80%를 나타낸다. M9 - M5, 만노스 잔기 9-5개를 가진 올리고만노스는 진회색으로 표시된다. Hybrid 및 FHybrid, 즉 푸코실화가 존재하거나 또는 존재하지 않는 하이브리드 타입들은 회색으로 나타낸다. 복합체 타입 내 서브타입들은 연회색으로 나타내며, 이는 안테나 개수와 푸코실화에 따라 분류된다.
도 8 (A-B). 생물층 간섭 측정에 의한 hACE2 및 CR3022 Fab의 친화성 결정. (A) 고정된 단량체 RBD와 삼량체 RBD-8GS-I53-50A, RBD-12GS-I53-50A 및 RBD-16GS-I53-50A 구성성분에 대한 단량체 hACE2의 결합성 분석. (B) 고정된 단량체 RBD와 삼량체 RBD-8GS-I53-50A, RBD-12GS-I53-50A 및 RBD-16GS-I53-50A 구성성분들에 대한 CR3022 Fab의 결합성 분석. 6종의 분석물 농도에서 입수한 카이네틱 데이터를 1:1 결합 모델에 전체 피팅하여 친화성 상수 (표 5)를 구하였다.
도 9 (A-D). 부분 결합가 RBD 나노입자의 특징 규명. (A) RBD를 결합가 50%로 나열하는 음성 염색된 RBD-8GS-I53-50 나노입자, RBD-12GS-I53-50 나노입자 및 RBD-16GS-I53-50 나노입자의 대표적인 전자 현미경 사진. 샘플을 냉동/해동 사이클 1회 수행한 후 사진을 촬영하였다. 기준자, 100 nm. (B) RBD를 50% 결합가로 나열하는 정제된 RBD-8GS-I53-50 나노입자, RBD-12GS-I53-50 나노입자 및 RBD-16GS-I53-50 나노입자의 SDS-PAGE. RBD-함유 I53-50A 서브유닛 및 비-변형된 I53-50A 서브유닛 모두 겔에서 볼 수 있다. (C) 냉동/해동 수행 전 및 후 50% 결합가의 RBD-8GS-I53-50 나노입자, RBD-12GS-I53-50 나노입자 및 RBD-16GS-I53-50 나노입자의 동적 광 산란 (DLS). 응집체나 비-조립된 구성성분들은 관찰되지 않았다. (D) 50% 결합가의 RBD-8GS-I53-50 나노입자, RBD-12GS-I53-50 나노입자 및 RBD-16GS-I53-50 나노입자들에 대한 UV/vis 흡광 스펙트럼. 샘플의 탁도는 320 nm에서의 낮은 흡광도에 의해 확인되는 바와 같이 낮았다.
도 10 (A-E). 28일 안정성 데이터. (A) 정제된 단량체 RBD, S-2P 삼량체, RBD-I53-50A 구성성분들 및 RBD-12GS-I53-50 나노입자에 대한 환원 및 비-환원 조건 하 SDS-PAGE 결과. 분석한 임의 온도에서 4주 인큐베이션한 후 임의의 면역원의 분해는 관찰되지 않았다. (B) 3가지 온도에서 4주 인큐베이션한 후 BLI에 의한 단량체 RBD, RBD-I53-50A 삼량체 성분 및 RBD-12GS-I53-50 나노입자에 대한 mACE2-Fc 및 CR3022 IgG의 결합 분석. 나노입자 성분 및 나노입자 BLI 실험에서 단량체 RBD를 참조 표준물질로 사용하였다. RBD-12GS-I53-50 나노입자는 4주 후 더 고온에서 최소 결합성을 상실하였으며; 나머지 항원들은 실험 기간 동안 임의의 mACE2-Fc 또는 CR3022 IgG 결합성을 상실하지 않았다. (C) UV/vis 분광학에서 근자외선 영역에서 최소 흡광도가 관찰되었는데, 이는 주위 온도에서 약 320 nm에서 현저한 흡광도가 관찰된 S-2P 삼량체를 제외하고는, 3가지 온도에서 4주간 인큐베이션한 후 응집체/미립자가 없다는 것을 의미한다. RBD-12GS-I53-50 나노입자 샘플은 22-27℃에서 좀더 이른 여러 시점에 320 nm 근처에서 비슷한 피크를 나타내었다 (부록 2 참조). (D) 3가지 농도에서 4주간 인큐베이션한 후 RBD-12GS-I53-50 나노입자 (상단) 및 S-2P 삼량체 (하단)의 nsEM. 모든 온도들에서 온전한 단분산 나노입자가 관찰되었으며, 분해 또는 응집은 관찰되지 않았다. S-2P 삼량체는 <-70 및 22-27℃ 샘플에서 잘 접힌 상태로 유지되었지만, 2-8℃에서 인큐베이션한 샘플에서는 언폴딩되었다. 기준자: RBD-12GS-I53-50, 100 nm; S-2P, 50 nm. (E) 3가지 온도에서 4주 인큐베이션한 후 RBD-12GS-I53-50 나노입자의 DLS. 어떤 온도에서도 응집체는 관찰되지 않았다.
도 11. 백신-유발된 Ab의 서브클래스 및 anti-스캐폴드 항체 역가. BALB/c 마우스에서 감작 후 (좌) 및 부스트 후 (우) 2주차에 (상단) 삼량체 I53-50A 구성성분, (중앙) 오량체 I53-50B 구성성분 및 (하단) 조립된 I53-50 나노입자에 특이적인 백신-유발된 IgG의 수준.
도 12 (A-D). B 세포 게이팅 전략 및 백신-유발된 면역 반응의 지속성. (A) RBD-특이적인 B 세포, 배중심 (GC) 전구체 및 B 세포 (CD38+/-GL7+), 및 B 세포 이소형을 평가하기 위한 대표적인 게이팅 전략. 상단 열, 살아있는 비-더블렛 (non-doublet) B 세포의 수를 측정하기 위한 게이팅 전략. 이들 세포는 중간 및 하단 열에 나타낸 바와 같이 추가로 분석하였다. 중간 열, AddaVax™가 첨가된 단량체 RBD 제형으로 면역화한 마우스의 대표적인 데이터. 디코이에 결합하지 않는 RBD+CD38+/-GL7+ 세포는 항원-특이적인 GC 전구체 및 B 세포로 카운트하였다. 하단 열, AddaVax™가 첨가된 RBD-12GS-I53-50 나노입자 제형으로 면역화한 마우스의 대표적인 데이터. GC 전구체 및 B 세포를 추가로 분석하여 B 세포 수용체 이소형의 특징을 규명하였다. (B-C) 부스트 후 20주 (RBD-16GS-I53-50) 또는 24주 (단량체 RBD, S-2P, RBD-8GS-I53-50 및 RBD-12GS-I53-50) 경과시 채취한 혈청에서의 (B) S-특이적인 IgG 및 (C) 슈도바이러스 중화 수준. MA-SARS-CoV-2가 기회 감염되지 않은 동물에서 각 군 당 2마리로 혈청을 수집하였다. (D) ELISpot에 의해 측정한, S-2P 삼량체 또는 RBD-16GS-I53-50 나노입자로 면역화된 BALB/c 마우스의 골수에서 S-2P-특이적인 Ab를 분비하는 세포의 개수. 부스트 후 17주차에 세포를 회수하였다 (패널 B 삽입도 참조). 동물 실험은 1회 수행하였다. 통계학적 유의성은 양측 비-대응 t 검정으로 확인하였다. *, p = 0.02.
인용된 모든 참조문헌들은 그 전체가 원용에 의해 본 명세서에 병합된다. 본 출원에서 달리 언급되지 않은 한, 이용된 기법들은 다음과 같이 잘 공지된 여러 참조문헌들에서 찾아볼 수 있다: Molecular Cloning: A Laboratory Manual (Sambrook, et al., 1989, Cold Spring Harbor Laboratory Press), Gene Expression Technology (Methods in Enzymology, Vol. 185, edited by D. Goeddel, 1991. Academic Press, San Diego, CA), "Guide to Protein Purification" in Methods in Enzymology (M.P. Deutshcer, ed., (1990) Academic Press, Inc.); PCR Protocols: A Guide to Methods and Applications (Innis, et al. 1990. Academic Press, San Diego, CA), Culture of Animal Cells: A Manual of Basic Technique, 2nd Ed. (R.I. Freshney. 1987. Liss, Inc. New York, NY), Gene Transfer and Expression Protocols, pp. 109-128, ed. E.J. Murray, The Humana Press Inc., Clifton, N.J.), 및 the Ambion 1998 Catalog (Ambion, Austin, TX).
본원에서, 단수 형태 ("a", "an" 및 "the")는 문맥상 달리 명시되지 않은 한 복수의 언급도 포괄한다.
본원에서, "약"은 언급된 매개변수에 대한 +/- 5%를 의미한다.
본원에서, 아미노산 잔기는 다음과 같이 약어로 표시된다: 알라닌 (Ala; A), 아스파라긴 (Asn; N), 아스파르트산 (Asp; D), 아르기닌 (Arg; R), 시스테인 (Cys; C), 글루탐산 (Glu; E), 글루타민 (Gln; Q), 글리신 (Gly; G), 히스티딘 (His; H), 이소루신 (Ile; I), 루신 (Leu; L), 라이신 (Lys; K), 메티오닌 (Met; M), 페닐알라닌 (Phe; F), 프롤린 (Pro; P), 세린 (Ser; S), 트레오닌 (Thr; T), 트립토판 (Trp; W), 티로신 (Tyr; Y), 및 발린 (Val; V).
본 발명의 임의 측면에서 모든 구현예들은 문맥상 달리 명시되지 않은 한 조합하여 이용할 수 있다.
문맥상 명확하게 달리 요구되지 않은 한, 명세서 및 청구항 전체에서 '포함한다', '포함하는' 등의 용어들은 배타적이거나 또는 전부 망라한다는 의미와는 반대되는 포괄적인 의미로, 즉, "포함하지만, 이로 제한되지 않는"의 의미로 해석되어야 한다. 단수 또는 복수를 사용하는 용어들 역시 각각 복수 및 단수를 포함한다. 아울러, 용어 "여기에서", "전술한" 및 "후술한" 및 이와 유사한 의미를 가진 용어들은 본 출원에 사용되는 경우 본 출원의 어떤 특정한 부분이 아닌 본 출원의 전체를 나타내는 것이다.
제1 측면에서, 본 발명은 서열번호 1-84, 138-146 및 167-184로 이루어진 군으로부터 선택되는 아미노산 서열에 대해 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99% 또는 적어도 100% 동일한 아미노산 서열을 포함하되, X1이 생략되거나 또는 아미노산 링커이고, 괄호 안 서열이 선택적으로, 존재할 수 있거나 또는 선택 잔기 중 일부 또는 전부 생략될 수 있는, 폴리펩타이드를 제공한다.
후술한 실시예에 나타낸 바와 같이, 이러한 측면의 폴리펩타이드는 SARS-CoV-2에 대항하여 강력한 보호성 항체 반응을 유발하는 자가-조립성 단백질 나노입자 면역원을 구축하는데 이용할 수 있다. 나노입자 백신은 5배 이상 낮은 용량에도 불구하고 융합 전-안정화된 S 엑토도메인 삼량체 (prefusion-stabilized S ectodomain trimer)보다 거의 10배 높은 중화 항체 역가를 유도한다. 나노입자 면역원에 의해 생성된 항체들은 여러가지 개별 에피토프들을 표적화하므로, 이는 이들 항체가 탈출 돌연변이에 쉽게 취약하지 않으며, 회복기 인간 혈청보다 현저하게 낮은 결합:중화 비율을 나타내어, 백신-관련 증가된 호흡기 질환의 위험을 최소화할 수 있음을 시사해준다.
본 발명의 이러한 측면에 대한 예시적인 폴리펩타이드의 아미노산 서열을 아래에 나타낸다.
표 1
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>HexaPro-12GS-He-I5350A*-His:
(MFVFLVLLPLVSSQC)VNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSPIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGPALQIPFPMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTPSALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQ(GSGSGGSGGSGSEKAAKAEEAAR)KMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE(GGSHHHHHHHH) (서열번호 138)
>HexaPro-FO-12GS-He-I5350A*-His:
(MFVFLVLLPLVSSQC)VNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSPIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGPALQIPFPMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTPSALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQ(GS)(GYIPEAPRDGQAYVRKDGEWVLLSTFL)(GSGSGGSGGSGSEKAAKAEEAAR)KMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE(GGSHHHHHHHH) (서열번호 139)
>HexaPro-delHR2-12GS-He-I5350A*-His:
(MFVFLVLLPLVSS)QC)VNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSPIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGPALQIPFPMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTPSALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHT(GSGSGGSGGSGSEKAAKAEEAAR)KMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE(GGSHHHHHHHH) (서열번호 140)
>HexaPro-delHR2-FO-12GS-He-I5350A*-His:
(MFVFLVLLPLVSS)QC)VNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSPIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGPALQIPFPMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTPSALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHT(GS)(GYIPEAPRDGQAYVRKDGEWVLLSTFL)(GSGSGGSGGSGSEKAAKAEEAAR)KMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE(GGSHHHHHHHH) (서열번호 141)
RBD-noRpk-50A 변이체
>SARS-CoV-2 RBD_N501Y_16GS-he-I53-50A*-His (UK):
(MGILPSPGMPALLSLVSLLSVLLMGCVAETGT)RFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTYGVGYQPYRVVVLSFELLHAPATVCGPKKST(GGSGGSGSGGSGGSGSEKAAKAEEAAR)KMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE(GGSHHHHHHHH) (서열번호 142)
>SARS-CoV-2 RBD_K417N_E484K_N501Y_16GS-he-I53-50A*-His (남아프리카)
(MGILPSPGMPALLSLVSLLSVLLMGCVAETGT)RFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGNIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVKGFNCYFPLQSYGFQPTYGVGYQPYRVVVLSFELLHAPATVCGPKKST(GGSGGSGSGGSGGSGSEKAAKAEEAAR)KMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE(GGSHHHHHHHH) (서열번호 143)
>SARS-CoV-2_RBD-noRpk_16GS_I53-50A*_Brazil-ver_K417T_E484K_N501Y (브라질):
(MGILPSPGMPALLSLVSLLSVLLMGCVAETGT)RFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGTIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVKGFNCYFPLQSYGFQPTYGVGYQPYRVVVLSFELLHAPATVCGPKKST(GGSGGSGSGGSGGSGSEKAAKAEEAAR)KMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE(GGSHHHHHHHH) (서열번호 144)
>SARS-CoV-2_RBD-noRpk_16GS_I53-50A*_E484K:
(MGILPSPGMPALLSLVSLLSVLLMGCVAETGT)RFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVKGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKST(GGSGGSGSGGSGGSGSEKAAKAEEAAR)KMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE(GGSHHHHHHHH) (서열번호 145)
>SARS-CoV-2_RBD-noRpk_16GS_I53-50A*_L452R:
(MGILPSPGMPALLSLVSLLSVLLMGCVAETGT)RFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYRYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKST(GGSGGSGSGGSGGSGSEKAAKAEEAAR)KMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE(GGSHHHHHHHH) (서열번호 146)
>SARS-CoV-2 RBD_N501Y_16GS-he-I53-50A*-His (UK):
(MGILPSPGMPALLSLVSLLSVLLMGCVA)RFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTYGVGYQPYRVVVLSFELLHAPATVCGPKKST(GGSGGSGSGGSGGSGSEKAAKAEEAAR)KMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE(GGSHHHHHHHH) (서열번호 147)
>SARS-CoV-2 RBD_K417N_E484K_N501Y_16GS-he-I53-50A*-His (남아프리카)
(MGILPSPGMPALLSLVSLLSVLLMGCVA)RFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGNIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVKGFNCYFPLQSYGFQPTYGVGYQPYRVVVLSFELLHAPATVCGPKKST(GGSGGSGSGGSGGSGSEKAAKAEEAAR)KMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE(GGSHHHHHHHH) (서열번호 148)
>SARS-CoV-2_RBD-noRpk_16GS_I53-50A*_Brazil-ver_K417T_E484K_N501Y (브라질):
(MGILPSPGMPALLSLVSLLSVLLMGCVA)RFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGTIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVKGFNCYFPLQSYGFQPTYGVGYQPYRVVVLSFELLHAPATVCGPKKST(GGSGGSGSGGSGGSGSEKAAKAEEAAR)KMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE(GGSHHHHHHHH) (서열번호 149)
>SARS-CoV-2_RBD-noRpk_16GS_I53-50A*_E484K:
(MGILPSPGMPALLSLVSLLSVLLMGCVA)RFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVKGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKST(GGSGGSGSGGSGGSGSEKAAKAEEAAR)KMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE(GGSHHHHHHHH) (서열번호 150)
>SARS-CoV-2_RBD-noRpk_16GS_I53-50A*_L452R:
(MGILPSPGMPALLSLVSLLSVLLMGCVA)RFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYRYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKST(GGSGGSGSGGSGGSGSEKAAKAEEAAR)KMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE(GGSHHHHHHHH) (서열번호 151)
다양한 구현예들에서, 폴리펩타이드는 서열번호 1-12 및 142-151로 이루어진 군으로부터 선택되는 아미노산 서열을 포함한다. 다양한 다른 구현예들에서, 폴리펩타이드는 서열번호 1-8로 이루어진 군 또는 서열번호 1-4, 서열번호 5-8로 이루어진 군으로부터, 또는 서열번호 1 및 5로 이루어진 군으로부터 선택되는 아미노산 서열에 대해 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99% 또는 적어도 100% 동일한 아미노산 서열을 포함하며, 아래 예들에서 예시적인 구현예들로 제공된다.
본 출원 전체에 사용된 바와 같이, 용어 "폴리펩타이드"는 가장 넓은 의미로 사용되며, 정규 (canonical) 아미노산 및 비-정규 (non-canonical) 아미노산을 비롯한 서브유닛 D-아미노산 또는 L-아미노산의 서열을 지칭한다. 본원에 기술된 폴리펩타이드는 화학적으로 합성하거나 또는 재조합에 의해 발현시킬 수 있다. 폴리펩타이드는 PEG (PEGylation), HES화 (HESylation), PAS화 (PASylation), 당화에 의해서와 같이, 생체내 반감기 증가를 촉진하기 위해 다른 화합물이 연결되거나, 또는 Fc-융합 또는 탈면역화 (deimmunized) 변이체로서 제조할 수 있다. 이러한 연결은 당해 기술 분야의 당업자가 이해하는 바와 같이 공유 연결 또는 비-공유 연결일 수 있다.
제2 측면에서, 본 발명은 본 발명의 제1 측면의 임의 구현예 또는 구현예들의 조합에 따른 복수의 폴리펩타이드를 포함하는 나노입자를 제공한다. 이러한 측면에서, 본 발명의 제1 측면의 복수의 폴리펩타이드 (2, 3, 4, 5, 10. 20, 25, 50, 60, 100 또는 그 이상)가 임의의 적절한 나노입자에 존재한다.
본원의 임의 구현예 또는 측면에 따른 나노입자는, 비-제한적으로 직경 약 10 nm 내지 약 100 nm를 비롯해 의도한 용도에 적합한 임의 크기일 수 있다.
제3 측면에서, 본 발명은
(a) 각각의 제1 어셈블리가 동일한 복수의 제1 단백질을 포함하는, 복수의 제1 어셈블리; 및
(b) 각각의 제2 어셈블리가 동일한 복수의 제2 단백질을 포함하는, 복수의 제2 어셈블리를 포함하며,
제1 단백질의 아미노산 서열이 제2 단백질의 서열과 다르고,
복수의 제1 어셈블리가 복수의 제2 어셈블리와 비-공유 상호작용해 나노입자를 형성하고,
나노입자가 그 표면에 하나 이상의 제2 단백질에 존재하는 SARS-CoV-2 항원 또는 이의 변이체 또는 상동체의 면역원성 부분을 나열하는, 나노입자를 제공한다.
이러한 측면에서, 나노입자는 제1 어셈블리와 제2 어셈블리의 비-공유 상호작용에 의해 형성된 3차원 구조를 형성한다. 제1 폴리펩타이드들 여러개 (2, 3, 4, 5, 6 또는 그보다 많은 수)가 자기-조립해 제1 어셈블리를 형성하고, 제2 폴리펩타이드들 여러개 (2, 3, 4, 5, 6 또는 그보다 많은 수)가 자기-조립해 제2 어셈블리를 형성한다. 개개 자기-조립성 단백질들 간의 비-공유 상호작용을 통해 제1 단백질들은 제1 어셈블리로 자기-조립되고, 제2 단백질들은 제2 어셈블리로 자기-조립된다. 복수의 제1 어셈블리 및 복수의 제2 어셈블리는 이후 계면을 통해 비-공유적으로 자기-조립되어 나노입자를 만들다. 제1 어셈블리에서 제1 폴리펩타이드의 개수는 제2 어셈블리에서 제2 폴리펩타이드의 개수와 동일하거나 또는 다를 수 있다. 본 발명의 나노입자는, 비-제한적으로 사면체, 팔면체, 이십면체, 정십이면체 및 이들의 절두된 형태 (truncated form)를 포함하여, 의도한 용도에 적합한 임의 형태 및/또는 대칭성을 가질 수 있다. 예시적인 일 구현예에서, 각각의 제1 어셈블리는 오량체이고, 각각의 제2 어셈블리는 삼량체이다.
제1 어셈블리와 제2 어셈블리의 나노입자로의 조립은 무작위가 아니지만, 다양한 어셈블리들 간 (즉, 제1 어셈블리들 간의 상호작용의 누적 효과, 제2 어셈블리들 간의 상호작용, 및 제1 어셈블리와 제2 어셈블리 간의 상호작용)의 비-공유 상호작용 (예를 들어, 수소 결합, 정전기, 반 데르 발스, 소수성 등)에 의해 인가된다. 그래서, 본 발명의 나노입자는, 제1 어셈블리와 제2 어셈블리가 고도로 정렬된 구조를 가진 나노입자로 배향되는, 대칭적으로 반복되는, 비-천연성, 비-공유적, 단백질-단백질 계면을 포함한다. 나노입자의 형성은 제1 어셈블리와 제2 어셈블리의 비-공유적 상호작용에 의한 것이지만, 일부 구현예에서, 일단 형성되면, 나노입자는 제1 어셈블리의 단백질과 제2 어셈블리의 단백질 간의 공유 연결을 통해 안정될 수 있다. 비-제한적으로 이황화 결합 및 이소펩타이드 연결을 포함한 임의의 적절한 공유 연결이 이용될 수 있다.
본 발명의 어셈블리를 형성하는데 적합한 제1 단백질 및 제2 단백질은 주어진 나노입자에 따라 적절한 임의 길이일 수 있다. 제1 단백질 및 제2 단백질은 아미노산 30-250개 길이일 수 있다.
일 구현예에서, 제2 단백질은 서열번호 85-124 또는 185-193 (표 2)으로 이루어진 군으로부터 선택되는 아미노산 서열에 대해 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99% 또는 적어도 100% 동일한 아미노산 서열을 포함하되, 하나 이상의 제2 단백질에서 X1은 SARS-CoV-2 항원 또는 이의 변이체 또는 상동체의 면역원성 부분을 포함하고, X2는 생략되거나 또는 아미노산 링커이고, 괄호 안 잔기들은 선택적이다. 선택 잔기는 존재할 수 있거나, 또는 선택 잔기의 일부 (즉, 1, 2, 3, 4, 5, 6 또는 그보다 많은 수) 또는 전부 생략될 수 있다.
표 2
단백질 명 단백질 유형 발현 서열 (괄호 안에는 선택 잔기를 나타냄)
SARS-CoV-2 RBD-I53-50A*-16GS-he-His SARS-CoV-2-I53-50A 융합 단백질 X1- GGSGGSGSGGSGGSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE (서열번호 85)
X1- (X2)KMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE (서열번호 86)

X1- GGSGGSGSGGSGGSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE(GGSHHHHHHHH) (서열번호 87)

X1- (X2)KMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE(GGSHHHHHHHH) (서열번호 88)
SARS-CoV-2 RBD-I53-50A*-8GS-he-His SARS-CoV-2-I53-50A 융합 단백질 X1-GGSGGSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE (서열번호 89)

X1-(X2)KMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE (서열번호 90)

X1-GGSGGSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE(GGSHHHHHHHH) (서열번호 91)

X1-(X2)KMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE(GGSHHHHHHHH) (서열번호 92)
SARS-CoV-2 RBD-I53-50A*-12GS-he-His SARS-CoV-2-I53-50A 융합 단백질 X1-GSGSGGSGGSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE (서열번호 93)

X1-(X2)KMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE (서열번호 94)

X1-GSGSGGSGGSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE(GGSHHHHHHHH) (서열번호 95)

X1-(X2)KMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE(GGSHHHHHHHH) (서열번호 96)
SARS-CoV-2 2PSGAG-S-TEV-FO-I53-50A*-12GS-he-His
(+ foldon)		 SARS-CoV-2-I53-50A 융합 단백질 X1-gsgrenlyfqggggsgyipeaprdgqayvrkdgewvllstflgGSGSGGSGGSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE (서열번호 97)

X1-(X2)KMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE (서열번호 98)

X1-gsgrenlyfqggggsgyipeaprdgqayvrkdgewvllstflgGSGSGGSGGSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE(GGSHHHHHHHH) (서열번호 99)

X1-(X2)KMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE(GGSHHHHHHHH) (서열번호 100)
SARS-CoV-2 2PSGAG-S-I53-50A*-12GS-he-His(- foldon) SARS-CoV-2-I53-50A 융합 단백질 X1- GSGSGGSGGSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE (서열번호 101)

X1- (X2)KMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE (서열번호 102)

X1- GSGSGGSGGSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE(GGSHHHHHHHH) (서열번호 103)

X1-(X2)RKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATE(GGSHHHHHHHH) (서열번호 104)
SARS-CoV-2 RBD-I3-01*-secOpt-8GS-he-His SARS-CoV-2-I3-01 융합 단백질 X1- GGSGGSGSEKAAKAEEAARMEELFKEHKIVAVLRANSVEEAKKKALAVFLGGVDLIEITFTVPDADTVIKELSFLKEMGAIIGAGTVTSVEQAREAVESGAEFIVSPHLDEEISQFAKEEGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVEAMKGPFPNVKFVPTGGVNLDNVAEWFEAGVQAVGVGEALNEGTPVEVAEKAKAFVEKIEGATE (서열번호 105)
X1- (X2)MEELFKEHKIVAVLRANSVEEAKKKALAVFLGGVDLIEITFTVPDADTVIKELSFLKEMGAIIGAGTVTSVEQAREAVESGAEFIVSPHLDEEISQFAKEEGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVEAMKGPFPNVKFVPTGGVNLDNVAEWFEAGVQAVGVGEALNEGTPVEVAEKAKAFVEKIEGATE (서열번호 106)

X1- GGSGGSGSEKAAKAEEAARMEELFKEHKIVAVLRANSVEEAKKKALAVFLGGVDLIEITFTVPDADTVIKELSFLKEMGAIIGAGTVTSVEQAREAVESGAEFIVSPHLDEEISQFAKEEGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVEAMKGPFPNVKFVPTGGVNLDNVAEWFEAGVQAVGVGEALNEGTPVEVAEKAKAFVEKIEGATE(GGSHHHHHHHH) (서열번호 107)

X1- (X2)MEELFKEHKIVAVLRANSVEEAKKKALAVFLGGVDLIEITFTVPDADTVIKELSFLKEMGAIIGAGTVTSVEQAREAVESGAEFIVSPHLDEEISQFAKEEGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVEAMKGPFPNVKFVPTGGVNLDNVAEWFEAGVQAVGVGEALNEGTPVEVAEKAKAFVEKIEGATE(GGSHHHHHHHH) (서열번호 108)
SARS-CoV-2 RBD-I3-01*-secOpt-12GS-he-His SARS-CoV-2-I3-01 융합 단백질 X1- GSGSGGSGGSGSEKAAKAEEAARMEELFKEHKIVAVLRANSVEEAKKKALAVFLGGVDLIEITFTVPDADTVIKELSFLKEMGAIIGAGTVTSVEQAREAVESGAEFIVSPHLDEEISQFAKEEGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVEAMKGPFPNVKFVPTGGVNLDNVAEWFEAGVQAVGVGEALNEGTPVEVAEKAKAFVEKIEGATE (서열번호 109)
X1- (X2)MEELFKEHKIVAVLRANSVEEAKKKALAVFLGGVDLIEITFTVPDADTVIKELSFLKEMGAIIGAGTVTSVEQAREAVESGAEFIVSPHLDEEISQFAKEEGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVEAMKGPFPNVKFVPTGGVNLDNVAEWFEAGVQAVGVGEALNEGTPVEVAEKAKAFVEKIEGATE (서열번호 110)

X1- GSGSGGSGGSGSEKAAKAEEAARMEELFKEHKIVAVLRANSVEEAKKKALAVFLGGVDLIEITFTVPDADTVIKELSFLKEMGAIIGAGTVTSVEQAREAVESGAEFIVSPHLDEEISQFAKEEGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVEAMKGPFPNVKFVPTGGVNLDNVAEWFEAGVQAVGVGEALNEGTPVEVAEKAKAFVEKIEGATE(GGSHHHHHHHH) (서열번호 111)

X1- (X2)MEELFKEHKIVAVLRANSVEEAKKKALAVFLGGVDLIEITFTVPDADTVIKELSFLKEMGAIIGAGTVTSVEQAREAVESGAEFIVSPHLDEEISQFAKEEGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVEAMKGPFPNVKFVPTGGVNLDNVAEWFEAGVQAVGVGEALNEGTPVEVAEKAKAFVEKIEGATE(GGSHHHHHHHH) (서열번호 112)
SARS-CoV-2 RBD-I3-01*-secOpt-16GS-he-His SARS-CoV-2-I3-01 융합 단백질 X1- GGSGGSGSGGSGGSGSEKAAKAEEAARMEELFKEHKIVAVLRANSVEEAKKKALAVFLGGVDLIEITFTVPDADTVIKELSFLKEMGAIIGAGTVTSVEQAREAVESGAEFIVSPHLDEEISQFAKEEGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVEAMKGPFPNVKFVPTGGVNLDNVAEWFEAGVQAVGVGEALNEGTPVEVAEKAKAFVEKIEGATE (서열번호 113)
X1- (X2)MEELFKEHKIVAVLRANSVEEAKKKALAVFLGGVDLIEITFTVPDADTVIKELSFLKEMGAIIGAGTVTSVEQAREAVESGAEFIVSPHLDEEISQFAKEEGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVEAMKGPFPNVKFVPTGGVNLDNVAEWFEAGVQAVGVGEALNEGTPVEVAEKAKAFVEKIEGATE (서열번호 114)

X1- GGSGGSGSGGSGGSGSEKAAKAEEAARMEELFKEHKIVAVLRANSVEEAKKKALAVFLGGVDLIEITFTVPDADTVIKELSFLKEMGAIIGAGTVTSVEQAREAVESGAEFIVSPHLDEEISQFAKEEGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVEAMKGPFPNVKFVPTGGVNLDNVAEWFEAGVQAVGVGEALNEGTPVEVAEKAKAFVEKIEGATE(GGSHHHHHHHH) (서열번호 115)

X1- (X2)MEELFKEHKIVAVLRANSVEEAKKKALAVFLGGVDLIEITFTVPDADTVIKELSFLKEMGAIIGAGTVTSVEQAREAVESGAEFIVSPHLDEEISQFAKEEGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVEAMKGPFPNVKFVPTGGVNLDNVAEWFEAGVQAVGVGEALNEGTPVEVAEKAKAFVEKIEGATE(GGSHHHHHHHH) (서열번호 116)
SARS-CoV-2 2PSGAG-S-TEV-FO-I3-01*-secOpt-12GS-he-His(+ foldon) SARS-CoV-2-I3-01 융합 단백질 X1-gsgrenlyfqggggsgyipeaprdgqayvrkdgewvllstflgGSGSGGSGGSGSEKAAKAEEAARMEELFKEHKIVAVLRANSVEEAKKKALAVFLGGVDLIEITFTVPDADTVIKELSFLKEMGAIIGAGTVTSVEQAREAVESGAEFIVSPHLDEEISQFAKEEGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVEAMKGPFPNVKFVPTGGVNLDNVAEWFEAGVQAVGVGEALNEGTPVEVAEKAKAFVEKIEGATE (서열번호 117)

X1-(X2)MEELFKEHKIVAVLRANSVEEAKKKALAVFLGGVDLIEITFTVPDADTVIKELSFLKEMGAIIGAGTVTSVEQAREAVESGAEFIVSPHLDEEISQFAKEEGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVEAMKGPFPNVKFVPTGGVNLDNVAEWFEAGVQAVGVGEALNEGTPVEVAEKAKAFVEKIEGATE (서열번호 118)

X1- gsgrenlyfqggggsgyipeaprdgqayvrkdgewvllstflgGSGSGGSGGSGSEKAAKAEEAARMEELFKEHKIVAVLRANSVEEAKKKALAVFLGGVDLIEITFTVPDADTVIKELSFLKEMGAIIGAGTVTSVEQAREAVESGAEFIVSPHLDEEISQFAKEEGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVEAMKGPFPNVKFVPTGGVNLDNVAEWFEAGVQAVGVGEALNEGTPVEVAEKAKAFVEKIEGATE(GGSHHHHHHHH) (서열번호 119)

X1- (X2)MEELFKEHKIVAVLRANSVEEAKKKALAVFLGGVDLIEITFTVPDADTVIKELSFLKEMGAIIGAGTVTSVEQAREAVESGAEFIVSPHLDEEISQFAKEEGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVEAMKGPFPNVKFVPTGGVNLDNVAEWFEAGVQAVGVGEALNEGTPVEVAEKAKAFVEKIEGATE(GGSHHHHHHHH) (서열번호 120)
SARS-CoV-2 2PSGAG-S-I3-01*-secOpt-12GS-he-His(- foldon) SARS-CoV-2-I3-01 융합 단백질 X1- GSGSGGSGGSGSEKAAKAEEAARMEELFKEHKIVAVLRANSVEEAKKKALAVFLGGVDLIEITFTVPDADTVIKELSFLKEMGAIIGAGTVTSVEQAREAVESGAEFIVSPHLDEEISQFAKEEGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVEAMKGPFPNVKFVPTGGVNLDNVAEWFEAGVQAVGVGEALNEGTPVEVAEKAKAFVEKIEGATE (서열번호 121)

X1- (X2)MEELFKEHKIVAVLRANSVEEAKKKALAVFLGGVDLIEITFTVPDADTVIKELSFLKEMGAIIGAGTVTSVEQAREAVESGAEFIVSPHLDEEISQFAKEEGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVEAMKGPFPNVKFVPTGGVNLDNVAEWFEAGVQAVGVGEALNEGTPVEVAEKAKAFVEKIEGATE (서열번호 122)

X1- GSGSGGSGGSGSEKAAKAEEAARMEELFKEHKIVAVLRANSVEEAKKKALAVFLGGVDLIEITFTVPDADTVIKELSFLKEMGAIIGAGTVTSVEQAREAVESGAEFIVSPHLDEEISQFAKEEGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVEAMKGPFPNVKFVPTGGVNLDNVAEWFEAGVQAVGVGEALNEGTPVEVAEKAKAFVEKIEGATE(GGSHHHHHHHH) (서열번호 123)

X1- (X2)MEELFKEHKIVAVLRANSVEEAKKKALAVFLGGVDLIEITFTVPDADTVIKELSFLKEMGAIIGAGTVTSVEQAREAVESGAEFIVSPHLDEEISQFAKEEGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVEAMKGPFPNVKFVPTGGVNLDNVAEWFEAGVQAVGVGEALNEGTPVEVAEKAKAFVEKIEGATE(GGSHHHHHHHH) (서열번호 124)
I53_dn5A W16E 디그레이즈드 나노입자 단백질 (METDTLLLWVLLLWVPGSTGDYKDE)KKYDGSKLRIGILHARENAEIILALVLGALKRLQEFGVKRENIIIETVPGSFELPYGSKLFVEKQKRLGKPLDAIIPIGVLIKGSTMHFEYICDSTTHQLMKLNFELGIPVIFGVLTCLTDEQAEARAGLIEGKMHNHGEDWGAAAVEMATKFN(LEGSEQKLISEEDLHHHHHH) (서열번호 185)
I53_dn5A L29N 디그레이즈드 나노입자 단백질 (METDTLLLWVLLLWVPGSTGDYKDE)KKYDGSKLRIGILHARWNAEIILALVLGANKRLQEFGVKRENIIIETVPGSFELPYGSKLFVEKQKRLGKPLDAIIPIGVLIKGSTMHFEYICDSTTHQLMKLNFELGIPVIFGVLTCLTDEQAEARAGLIEGKMHNHGEDWGAAAVEMATKFN(LEGSEQKLISEEDLHHHHHH) (서열번호 186)
I53_dn5A 'mut101' [ T116N / L118D / T119K ] 디그레이즈드 나노입자 단백질 (METDTLLLWVLLLWVPGSTGDYKDE)KKYDGSKLRIGILHARWNAEIILALVLGALKRLQEFGVKRENIIIETVPGSFELPYGSKLFVEKQKRLGKPLDAIIPIGVLIKGSTMHFEYICDSTTHQLMKLNFELGIPVIFGVLNCDKDEQAEARAGLIEGKMHNHGEDWGAAAVEMATKFN(LEGSEQKLISEEDLHHHHHH) (서열번호 187)
I53_dn5A T116N 디그레이즈드 나노입자 단백질 (METDTLLLWVLLLWVPGSTGDYKDE)KKYDGSKLRIGILHARWNAEIILALVLGALKRLQEFGVKRENIIIETVPGSFELPYGSKLFVEKQKRLGKPLDAIIPIGVLIKGSTMHFEYICDSTTHQLMKLNFELGIPVIFGVLNCLTDEQAEARAGLIEGKMHNHGEDWGAAAVEMATKFN(LEGSEQKLISEEDLHHHHHH) (서열번호 188)
I53_dn5A L118D 디그레이즈드 나노입자 단백질 (METDTLLLWVLLLWVPGSTGDYKDE)KKYDGSKLRIGILHARWNAEIILALVLGALKRLQEFGVKRENIIIETVPGSFELPYGSKLFVEKQKRLGKPLDAIIPIGVLIKGSTMHFEYICDSTTHQLMKLNFELGIPVIFGVLTCDTDEQAEARAGLIEGKMHNHGEDWGAAAVEMATKFN(LEGSEQKLISEEDLHHHHHH) (서열번호 189)
I53_dn5A T119K 디그레이즈드 나노입자 단백질 (METDTLLLWVLLLWVPGSTGDYKDE)KKYDGSKLRIGILHARWNAEIILALVLGALKRLQEFGVKRENIIIETVPGSFELPYGSKLFVEKQKRLGKPLDAIIPIGVLIKGSTMHFEYICDSTTHQLMKLNFELGIPVIFGVLTCLKDEQAEARAGLIEGKMHNHGEDWGAAAVEMATKFN(LEGSEQKLISEEDLHHHHHH) (서열번호 190)
I53_dn5A.1 디그레이즈드 나노입자 단백질 (METDTLLLWVLLLWVPGSTGDYKDEMG)KYDGSKLRIGILHARGNAEIILALVLGALKRLQEFGVKRENIIIETVPGSFELPYGSKLFVEKQKRLGKPLDAIIPIGVLIRGSTPHFDYIADSTTHQLMKLNFELGIPVIFGVITADTDEQAEARAGLIEGKMHNHGEDWGAAAVEMATKFN(LEGSEQKLISEEDLHHHHHH) (서열번호 191)
I53_dn5A.1 W16E 디그레이즈드 나노입자 단백질 (METDTLLLWVLLLWVPGSTGDYKDEMG)KYDGSKLRIGILHARENAEIILALVLGALKRLQEFGVKRENIIIETVPGSFELPYGSKLFVEKQKRLGKPLDAIIPIGVLIRGSTPHFDYIADSTTHQLMKLNFELGIPVIFGVITADTDEQAEARAGLIEGKMHNHGEDWGAAAVEMATKFN(LEGSEQKLISEEDLHHHHHH) (서열번호 192)
I53_dn5A.2 디그레이즈드 나노입자 단백질 (METDTLLLWVLLLWVPGSTGDYKDEMG)KYDGSKLRIGILHARGNAEIILELVLGALKRLQEFGVKRENIIIETVPGSFELPYGSKLFVEKQKRLGKPLDAIIPIGVLIRGSTAHFDYIADSTTHQLMKLNFELGIPVIFGVLTTESDEQAEERAGTKAGNHGEDWGAAAVEMATKFN(LEGSEQKLISEEDLHHHHHH) (서열번호 193)
이러한 제3 측면의 다양한 구현예들에서, 제2 단백질은 서열번호 85-88로 이루어진 군으로부터 선택되는 아미노산 서열에 대해 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99% 또는 적어도 100% 동일한 아미노산 서열을 포함한다. 다양한 다른 구현예들에서, 폴리펩타이드는 서열번호 85-88로 이루어진 군 또는 서열번호 85-86으로 이루어진 군으로부터 선택되는 아미노산 서열, 또는 서열번호 85의 아미노산 서열을 포함하며, 이는 하기 예들에서 예시적인 구현예로서 제공된다.
이러한 제3 측면에 따른 나노입자는 그 표면에 하나 이상의 제2 단백질에 존재하는 SARS-CoV-2 항원 또는 이의 변이체 또는 상동체의 면역원성 부분을 나열한다. 일 구현예에서, SARS-CoV-2 항원 또는 이의 변이체 또는 상동체의 면역원성 부분은 하나 이상의 제2 단백질과의 융합 단백질로 존재하며; 이는 나노입자에서 하나의 제2 단백질에 존재 (나노입자 상에 한 카피로 존재)하거나, 또는 나노입자에 존재하는 복수의 제2 단백질들에 존재할 수 있다. 다양한 구현예들에서, SARS-CoV-2 항원 또는 이의 변이체 또는 상동체는 나노입자 내 제2 단백질들 중 적어도 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% 또는 100%에 존재한다.
이들 융합 단백질에서, 제2 단백질은 SARS-CoV-2 항원 또는 이의 변이체 또는 상동체와 직접 연결되거나, 또는 제2 단백질은 SARS-CoV-2 항원 또는 이의 변이체 또는 상동체와 링커를 통해 연결될 수 있다. 본원 전체에서 사용되는 바와 같이, 링커는 폴리펩타이드 2개를 공유적으로 연결하기 위해 사용되는 짧은 (예를 들어, 2-30개의) 아미노산 서열이다. 임의의 적절한 링커 서열, 비-제한적으로 본원에 기술된 것을 이용할 수 있다.
임의의 적절한 SARS-CoV-2 항원 또는 이의 변이체 또는 상동체를 이용할 수 있다. 제3 측면의 일 구현예에서, 제2 단백질들 중 적어도 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% 또는 100%는 X1이 SARS-CoV-2 또는 이의 변이체 또는 상동체로부터 유래한 스파이크 (S) 단백질 세포외 도메인 (ECD) 아미노산 서열, S1 서브유닛 아미노산 서열, S2 서브유닛 아미노산 서열, S1 수용체 결합 도메인 (RBD) 아미노산 서열, 및/또는 N-말단 도메인 (NTD) 아미노산 서열에 대해 적어도 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100%의 아미노산 서열 동일성을 가진 아미노산 서열을 포함한다.
다양한 추가적인 구현예에서, 제2 단백질들 중 적어도 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% 또는 100%는 X1이 서열번호 125-137로 이루어진 군으로부터 선택되는 아미노산 서열에 대해 적어도 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100%의 아미노산 서열 동일성을 가진 아미노산 서열을 포함한다.
RFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKST (RBD) 서열번호 125
ETGTRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKST (RBD) 서열번호 126
QCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPSGAGSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIK (스파이크 (S) 단백질 세포외 도메인 (ECD)) 서열번호 127
(ETGT)QCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPSGAGSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIK (존재하거나 또는 생략될 수 있는 괄호 안 신호 펩타이드에 대해 N-말단 링커를 가진, 스파이크 (S) 단백질 세포외 도메인 (ECD)) 서열번호 128
MGILPSPGMPALLSLVSLLSVLLMGCVAETGTQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPSGAGSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIK (서열번호 129) mu 포스파타제 신호 펩타이드, ETGT는 신호 펩타이드 절단 후 잔류물로 남는다.
(MFVFLVLLPLVSSQC)VNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSPIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGPALQIPFPMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTPSALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQ (서열번호 130)
(MFVFLVLLPLVSSQC)VNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSPIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGPALQIPFPMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTPSALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHT (서열번호 131)
(QC)VNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSPIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGPALQIPFPMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTPSALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQ (서열번호 132)
(QC)VNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSPIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGPALQIPFPMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTPSALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHT (서열번호 133)
VNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSPIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGPALQIPFPMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTPSALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQ (서열번호 134)
VNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSPIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGPALQIPFPMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTPSALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHT (서열번호 135)
ETCTQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSPIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGPALQIPFPMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTPSALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQ (서열번호 136)
ETCTQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSPIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGPALQIPFPMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTPSALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHT (서열번호 137)
일 특정 구현예에서, 제2 단백질들 중 적어도 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% 또는 100%는 X1이 서열번호 125, 즉 하기 예에서 예시적인 구현예로서 제공된 SARS-CoV-2 RBD의 아미노산 서열에 대해 적어도 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100%의 아미노산 서열 동일성을 가진 아미노산 서열을 포함한다. 다양한 구현예들에서, 제2 단백질들 중 적어도 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% 또는 100%는 X1이, 비-제한적으로, 하기 자연 생성 돌연변이 또는 돌연변이들의 조합 중 하나를 포함하는 돌연변이 등의, K90N, K90T, G119S, Y126F, T151I, E157K, E157A, S167P, N174Y 및 L125R로 이루어진 군으로부터 선택되는 돌연변이를, 서열번호 125를 기준으로 1, 2, 3, 4, 5, 6, 7 또는 모두 8곳의 위치에서 포함한다:
N174Y (UK 변이체);
K90N/E157K/N174Y (남아프리카 변이체);
K90N 또는 T/E157K/N174Y (브라질 변이체); 또는
L125R (LA 변이체).
이들 자연 생성 변이체들의 아미노산 잔기 번호는 서열번호 125에서의 위치를 기준으로 하지만, 일반적으로는 스파이크 단백질에서의 이의 잔기 번호를 기준으로 기술한다 (즉, 스파이크에서 K417 = RBD에서 K90; 스파이크에서 G446 = RBD에서 G119; 스파이크에서 L452 = RBD에서 L125; 스파이크에서 Y453 = RBD에서 Y126; 스파이크에서 T478 = RBD에서 T151; 스파이크에서 E484 = RBD에서 E157; 스파이크에서 S494 = RBD에서 S167; 스파이크에서 N501 = RBD에서 N174).
다양한 추가적인 구현예들에서, 제2 단백질들 중 적어도 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% 또는 100%는 X1이, 비-제한적으로 하기 자연 생성 돌연변이 또는 돌연변이들의 조합 중 하나를 포함하는 돌연변이 등의, L18F, T20N, P26S, 잔기 69-70의 결손, D80A, D138Y, R190S, D215G, K417N, K417T, G446S, L452R, Y453F, T478I, E484K, S494P, N501Y, A570D, D614G, H655Y, P681H, A701V, T716L로 이루어진 군으로부터 선택되는 돌연변이를 서열번호 130을 기준으로 1, 2, 3, 4, 5, 6, 7 또는 모두 8곳의 위치에서 포함한다:
N501Y, 선택적으로, 잔기 69-70의 결손, A570D, D614G, P681H 및/또는 T716L 중 1, 2, 3, 4 또는 5종을 추가로 포함함 (UK 변이체);
K417N/E484K/N501Y, 선택적으로, L18F, D80A, D215G, D614G 및/또는 A701V 중 1, 2, 3, 4 또는 5종을 추가로 포함함 (남아프리카 변이체);
K417N 또는 T/E484K/N501Y, 선택적으로, L18F, T20N, P26S, D138Y, R190S, D614G 및/또는 H655Y 중 1, 2, 3, 4 또는 5종을 추가로 포함함 (브라질 변이체); 또는
L452R (LA 변이체).
당해 기술 분야의 당업자에 의해 이해되는 바와 같이, X1이 서열번호 125 (또는 개시된 임의의 다른 항원)의 아미노산 서열에 대해 적어도 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100%의 아미노산 서열 동일성을 가진 아미노산 서열을 포함하는 경우, 이는 아미노-말단 또는 카르복시-말단에 추가적인 아미노산을 가질 수 있다. 따라서, 예를 들어, X1이 서열번호 125의 아미노산 서열에 대해 적어도 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100%의 아미노산 서열 동일성을 가진 아미노산 서열을 포함하는 경우, X1은 서열번호 125를 기준으로 N-말단에 추가적인 아미노산 서열을 가진, 서열번호 126의 아미노산 서열을 포함할 수 있다.
추가적인 구현예에서, 제2 단백질들 중 적어도 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% 또는 100%에서 X1은 서열번호 125을 기준으로 K90N, K90T, E157K 및 N174Y로 이루어진 군으로부터 선택되는 돌연변이를 1, 2, 3 또는 모두 4종을 포함한다.
복수의 제2 어셈블리는 통틀어 한가지 SARS-CoV-2 항원을 포함할 수 있거나, 또는 2종 이상의 여러가지 SARS-CoV-2 항원들을 포함할 수 있다. 일 구현예에서, 복수의 제2 어셈블리는 통틀어 2종, 3종, 4종, 5종, 6종, 7종, 8종 또는 그보다 많은 종의 여러가지 SARS-CoV-2 항원들을 포함한다. 예시적인 이러한 일 구현예에서, 복수의 제2 어셈블리는 서열번호 1-84 중 어느 하나의 아미노산 서열을 포함하는 폴리펩타이드를 통틀어 2종, 3종, 4종, 5종, 6종, 7종, 8종 또는 그보다 많이 포함한다.
일 구현예에서, 제2 단백질들 중 적어도 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% 또는 100%에서 X1은 서열번호 125의 아미노산 서열을 포함한다. 다른 구현예에서, 제2 단백질의 100%는 X1이 서열번호 125의 아미노산 서열을 포함하고, 즉 제2 단백질들 모두 동일하다.
추가적인 구현예에서, 제2 어셈블리들 모두 서열번호 1-84 중 어느 하나의 아미노산 서열을 포함하는 하나 이상의 제2 단백질을 포함한다. 다른 구현예에서, 제2 단백질들 모두 서열번호 1-84 중 어느 하나의 아미노산 서열을 포함한다.
나노입자는 동일한 제1 단백질을 여러개 포함한다. 일 구현예에서, 제1 단백질은 서열번호 152-159로 이루어진 군으로부터 선택되는 아미노산 서열에 대해 적어도 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100% 동일한 아미노산 서열을 포함하며, 괄호 안 서열은 선택적으로, 존재할 수 있거나, 또는 선택 잔기들 중 일부 (즉, 1, 2, 3, 4, 5, 6 또는 그 이상) 또는 전부 생략될 수 있다. 특정 구현예에서, 제1 단백질은 서열번호 155의 아미노산 서열에 대해 적어도 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100% 동일한 아미노산 서열을 포함한다.
명칭 아미노산 서열 동정한 계면 잔기 계면에 인접하지 않은 표면 잔기
I53-50B
서열번호 152		 (M)NQHSHKDYETVRIAVVRARWHAEIVDACVSAFEAAMADIGGDRFAVDVFDVPGAYEIPLHARTLAETGRYGAVLGTAFVVNGGIYRHEFVASAVIDGMMNVQLSTGVPVLSAVLTPHRYRDSDAHTLLFLALFAVKGMEAARACVEILAAREKIAA I53-50B: 24, 28, 36, 124, 125, 127, 128, 129, 131, 132, 133, 135, 139 I53-50B: 6,7,8,9,10,11,13,18,20,21,34,38,39,40,43,44,48,51,63,67,70,87,101,105,118,143,147,152,153,154
I53-50B.1
서열번호 153		 (M)NQHSHKDHETVRIAVVRARWHAEIVDACVSAFEAAMRDIGGDRFAVDVFDVPGAYEIPLHARTLAETGRYGAVLGTAFVVNGGIYRHEFVASAVIDGMMNVQLDTGVPVLSAVLTPHRYRDSDAHTLLFLALFAVKGMEAARACVEILAAREKIAA I53-50B: 24, 28, 36, 124, 125, 127, 128, 129, 131, 132, 133, 135, 139 I53-50B: 6,7,8,9,10,11,13,18,20,21,34,38,39,40,43,44,48,51,63,67,70,87,101,105,118,143,147,152,153,154
I53-50B.1NegT2
서열번호 154		 (M)NQHSHKDHETVRIAVVRARWHAEIVDACVSAFEAAMRDIGGDRFAVDVFDVPGAYEIPLHARTLAETGRYGAVLGTAFVVDGGIYDHEFVASAVIDGMMNVQLDTGVPVLSAVLTPHEYEDSDADTLLFLALFAVKGMEAARACVEILAAREKIAA I53-50B: 24, 28, 36, 124, 125, 127, 128, 129, 131, 132, 133, 135, 139 I53-50B: 6,7,8,9,10,11,13,18,20,21,34,38,39,40,43,44,48,51,63,67,70,87,101,105,118,143,147,152,153,154
I53-50B.4PosT1
서열번호 155		 (M)NQHSHKDHETVRIAVVRARWHAEIVDACVSAFEAAMRDIGGDRFAVDVFDVPGAYEIPLHARTLAETGRYGAVLGTAFVVNGGIYRHEFVASAVINGMMNVQLNTGVPVLSAVLTPHNYDKSKAHTLLFLALFAVKGMEAARACVEILAAREKIAA I53-50B: 24, 28, 36, 124, 125, 127, 128, 129, 131, 132, 133, 135, 139 I53-50B: 6,7,8,9,10,11,13,18,20,21,34,38,39,40,43,44,48,51,63,67,70,87,101,105,118,143,147,152,153,154
I53-50-v4 오량체 구성성분
(MGSSHHHHHHSSGLVPRGS EQKLISEEDLGS)NQHSQKDQETVRIAVVRARWHAFIVDACVSAFEAAMRKIGGERFAVDVFDVPGAYEIPLHARTLAKTGRYGAVLGTAFVVNGGIYRHEFVASAVIDGMMNVQLDTGVPVLSAVLTPHNYDKSNAKTLLFLALFAVKGMEAARACVEILAAREKIAA(GSLEGS)(서열번호 156)
I53-50-v1 오량체 구성성분 B
(M)NQHSHKDHETVRIAVVRARWHAEIVDACVSAFEAAMRDIGGDRFAVDVFDVPGAYEIPLHARTLAETGRYGAVLGTAFVVNGGIYRHEFVASAVIDGMMNVQLDTGVPVLSAVLTPHNYDKSKAHTLLFLALFAVKGMEAARACVEILAAREKIAA(GS) (서열번호 157)
I53-50-v2 오량체 구성성분 B
(M)NQHSHKDHETVRIAVVRARWHAFIVDACVSAFEAAMRDIGGDRFAVDVFDVPGAYEIPLHARTLAETGRYGAVLGTAFVVNGGIYRHEFVASAVIDGMMNVQLDTGVPVLSAVLTPHNYDKSNAKTLLFLALFAVKGMEAARACVEILAAREKIAA(GS) (서열번호 158)
I53-50-v3 오량체 구성성분 B
(M)NQHSHKDHETVRIAVVRARWHAFIVDACVSAFEAAMRDIGGDRFAVDVFDVPGAYEIPLHARTLAETGRYGAVLGTAFVVNGGIYRHEFVASAVIDGMMNVQLDTGVPVLSAVLTPHNYDKSNAKTLLFLALFAVKGMEAARACVEILAAREKIAA(GS) (서열번호 159)
예시적인 구현예에서, 제1 단백질은 서열번호 155의 아미노산 서열을 포함한다. 다양한 추가적인 이러한 구현예에서, 하나 이상의 또는 복수의 (20%, 33%, 40%, 50%, 75% 등) 제2 어셈블리는 서열번호 85-88로 이루어진 군으로부터 선택되는 아미노산 서열을 포함하는 하나 이상의 제2 단백질을 포함하거나, 또는 제2 어셈블리들 모두 서열번호 85-88로 이루어진 군으로부터 선택되는 아미노산 서열을 포함하는 하나 이상의 제2 단백질을 포함한다.
일 특정 구현예에서,
(a) 제1 단백질은 서열번호 155의 아미노산 서열을 포함하고;
(b) 제2 단백질들 모두 서열번호 85의 아미노산 서열을 포함하되,
제2 단백질들 중 적어도 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% 또는 100%는 X1이 서열번호 125의 아미노산 서열에 대해 적어도 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100%의 아미노산 서열 동일성을 가진 아미노산 서열을 포함한다.
다른 특정 구현예에서,
(a) 제1 단백질은 서열번호 155의 아미노산 서열을 포함하고;
(b) 제2 단백질들은 모두 서열번호 85의 아미노산 서열을 포함하되,
제2 단백질들 중 적어도 50%, 60%, 70%, 80%, 90% 또는 100%는 X1이 서열번호 125의 아미노산 서열에 대해 적어도 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100%의 아미노산 서열 동일성을 가진 아미노산 서열을 포함한다.
추가적인 특정 구현예에서:
(a) 제1 단백질은 서열번호 155의 아미노산 서열을 포함하고;
(b) 제2 단백질들은 모두 서열번호 1-8로 이루어진 군으로부터 선택되는 아미노산 서열을 포함한다.
일 특정 구현예에서:
(a) 제1 단백질은 서열번호 155의 아미노산 서열을 포함하고;
(b) 제2 단백질들은 모두 서열번호 1 또는 5의 아미노산 서열을 포함한다.
본 발명은 본원의 임의 구현예 또는 구현예들의 조합에 따른 복수의 나노입자를 포함하는 조성물을 추가로 제공한다. 일 구현예에서, 조성물은 상기 기술된 특정 구현예들에 따른 복수의 나노입자를 포함한다.
추가적인 측면에서, 본 발명은 본원의 폴리펩타이드 또는 융합 단백질을 암호화하는 핵산을 제공한다. 핵산 서열은 RNA (예, mRNA) 또는 DNA를 포함할 수 있다. 이러한 핵산 서열은, 비-제한적으로, 폴리A 세포, 변형된 코자키 서열, 에피토프 태그를 암호화하는 서열, 유출 신호를 암호화하는 신호, 분비 신호를 암호화하는 서열, 핵 위치화 신호를 암호화하는 서열 및 원형질막 위치화 신호를 암호화하는 서열 등의, 암호화된 단백질의 발현 및/또는 정제를 촉진하는데 유용한 부가적인 서열을 포함할 수 있다. 당해 기술 분야의 당업자라면, 본 발명의 교시 내용을 기초로 어떤 핵산 서열이 본 발명의 단백질을 암호화하는 것인지 자명할 것이다.
제5 측면에서, 본 발명은 적절한 조절 서열에 작동가능하게 연결된 본원의 임의 구현예 또는 구현예들의 조합에 따른 단리된 핵산을 포함하는 발현 벡터를 제공한다. "발현 벡터"는 유전자 산물의 발현을 구현할 수 있는 임의의 조절 서열에 핵산 암호화 영역 또는 유전자를 작동가능하게 연결하는 벡터를 포함한다. 본원의 핵산 서열에 작동가능하게 연결된 "조절 서열"은 핵산 분자의 발현을 구현할 수 있는 핵산 서열이다. 조절 서열이 핵산 서열의 발현을 지시하는 기능을 하는 한, 조절 서열이 핵산 서열과 인접해야 하는 것은 아니다. 따라서, 예를 들어, 전사되지만 번역되진 않는 개입 서열들이 프로모터 서열과 핵산 서열 사이에 존재할 수 있으며, 프로모터 서열은 여전히 암호화 서열에 "작동가능하게 연결된" 것으로 간주될 수 있다. 다른 이러한 조절 서열로는, 비-제한적으로, 폴리아데닐화 신호, 종결 신호 및 리보솜 결합부를 포함한다. 이러한 발현 벡터는, 비-제한적으로, 플라스미드 및 바이러스-기반의 발현 벡터를 비롯해 당해 기술 분야에 공지된 임의 유형의 것일 수 있다. 포유류 시스템에서 개시된 핵산 서열의 발현을 인가하기 위해 사용되는 조절 서열은 (비-제한적으로, CMV, SV40, RSV, 액틴, EF 등의 다양한 임의의 프로모터에 의해 구동됨) 구성적 또는 (비-제한적으로, 테트라사이클린, 엑다이손 (ecdysone), 스테로이드-응답성 등의 다수의 임의의 유도성 프로모터에 의해 구동되는) 유도성일 수 있다.
제6 측면에서, 본 발명은 본원의 임의 구현예 또는 구현예들의 조합에 따른 폴리펩타이드, 나노입자, 조성물, 핵산 및/또는 발현 벡터를 포함하는 세포를 제공하며, 세포는 포유류 세포와 같은 진핵 생물 세포 또는 원핵 생물 세포일 수 있다. 일 구현예에서, 세포는 본 발명의 핵산 또는 발현 벡터로 일시적으로 또는 안정적으로 형질감염될 수 있다. 원핵 생물 세포 및 진핵 생물 세포의 발현 벡터 형질감염은 당해 기술 분야에 공지된 임의 기법으로 달성할 수 있다. 본 발명에 따른 폴리펩타이드를 생산하는 방법은 본 발명의 부가적인 일부이다. 이 방법은 (a) 본 발명의 이러한 측면에 따른 숙주를 폴리펩타이드의 발현을 보장하는 조건 하에 배양하는 단계, 및 (b) 선택적으로, 발현된 폴리펩타이드를 회수하는 단계를 포함한다.
제7 측면에서, 본 발명은 하기를 포함하는 약학적 조성물/백신을 제공한다:
(a) 본원의 구현예 또는 구현예들의 조합에 따른 폴리펩타이드, 나노입자, 조성물, 핵산, 발현 벡터 및/또는 세포; 및
(b) 약제학적으로 허용가능한 담체.
아래 예들에 나타낸 바와 같이, 나노입자 면역원은 SARS-CoV-2에 대항하여 강력한 보호성 항체 반응을 유발한다. 본 발명의 나노입자 백신은 5배 이상 낮은 용량에도 불구하고 융합 전-안정화된 S 엑토도메인 삼량체보다 거의 10배 높은 중화 항체 역가를 유도한다. 나노입자 면역원에 의해 생기는 항체는 여러가지 개별 에피토프들을 표적화하므로, 이는 나노입자가 탈출 돌연변이에 쉽게 취약하지 않을 수 있으며, 회복기 인간 혈청보다 현저하게 낮은 결합:중화 비율을 나타내어, 백신-관련 증가된 호흡 질환의 위험을 최소화할 수 있다는 것을 의미한다.
조성물/백신은 추가적으로 (a) 동결보호제 (lyoprotectant); (b) 계면활성제; (c) 증량제; (d) 긴장도 조정제; (e) 안정화제; (f) 보존제 및/또는 (g) 완충제를 포함할 수 있다. 일부 구현예에서, 약학적 조성물 내 완충제는 트리스 완충제, 히스티딘 완충제, 포스페이트 완충제, 사이트레이트 완충제 또는 아세테이트 완충제이다. 또한, 조성물은 동결보호제, 예를 들어 슈크로스, 소르비톨 또는 트레할로스를 함유할 수 있다. 특정 구현예에서, 조성물은 보존제, 예를 들어 벤즈알코늄 클로라이드, 벤즈에토늄, 클로로헥시딘, 페놀, m-크레졸, 벤질 알코올, 메틸파라벤, 프로필파라벤, 클로로부탄올, o-크레졸, p-크레졸, 클로로크레졸, 페닐머큐릭 나이트레이트, 티메로살, 벤조산 및 이들의 다양한 혼합물을 함유한다. 다른 구현예들에서, 조성물은 글리신과 같은 증량제를 함유한다. 또 다른 구현예에서, 조성물은 계면활성제, 예를 들어, 폴리소르베이트-20, 폴리소르베이트-40, 폴리소르베이트-60, 폴리소르베이트-65, 폴리소르베이트-80 폴리소르베이트-85, 폴록사머-188, 소르비탄 모노라우레이트, 소르비탄 모노팔미테이트, 소르비탄 모노스테아레이트, 소르비탄 모노올레이트, 소르비탄 트리라우레이트, 소르비탄 트리스테아레이트, 소르비탄 트리올레이트 또는 이들의 조합을 함유한다. 또한, 조성물은 긴장도 조정제, 예를 들어, 제형을 인간 혈액과 실질적으로 등장성 또는 삼투성 등장성으로 만드는 화합물을 함유할 수 있다. 예시적인 긴장도 조정제로는 슈크로스, 소르비톨, 글리신, 메티오닌, 만니톨, 덱스트로스, 이노시톨, 소듐 클로라이드, 아르기닌 및 아르기닌 하이드로클로라이드 등이 있다. 다른 구현예들에서, 조성물은 부가적으로 안정화제, 예를 들어, 동결건조된 형태 또는 액체 형태에서 나노구조의 화학적 및/또는 물리적 불안정성을 실질적으로 낮추거나 또는 방지하는 분자를 함유한다. 예시적인 안정화제로는 슈크로스, 소르비톨, 글리신, 이노시톨, 소듐 클로라이드, 메티오닌, 아르기닌 및 아르기닌 하이드로클로라이드 등이 있다.
나노입자는 조성물 내 단독 활성 물질일 수 있거나, 또는 조성물은, 비-제한적으로, 일반적으로 면역 시스템을 자극해 면역 반응을 전반적으로 개선하기 위한 보강제 등의, 의도한 용도에 적합한 하나 이상의 다른 물질을 더 포함할 수 있다. 임의의 적절한 보강제를 이용할 수 있다. 용어 "보강제"는 항원에 대한 면역 반응을 강화하는 화합물 또는 혼합물을 지칭한다. 예시적인 보강제로는, 비-제한적으로, Adju-Phos™, Adjumer™, 알부민-헤파린 미세입자, 조류 글루칸 (Algal Glucan), 알가물린 (Algammulin), 알럼 (Alum), 항원 제형, AS-2 보강제, 자가 수지상 세포, 자가 PBMC, Avridine™, B7-2, BAK, BAY R1005, 부피바카인 (bupivacaine), 부피바카인-HCl, BWZL, 칼시트리올, 칼슘 포스페이트 겔, CCR5 펩타이드, CFA, 콜레라 홀로톡신 (CT) 및 콜레라 독소 B 서브유닛 (CTB), 콜레라 독소 A1-서브유닛-단백질 A D-단편 융합 단백질, CpG, CRL1005, 사이토카인-함유 리포좀, D-무라팔미틴 (D-Murapalmitine), DDA, DHEA, 디프테리아 톡소이드, DL-PGL, DMPC, DMPG, DOC/알럼 복합체, Fowlpox, 프로인트 완전 보강제, 감마 이눌린, Gerbu 보강제, GM-CSF, GMDP, hGM-CSF, hIL-12 (N222L), hTNF-α, IFA, IFN-γ/pcDNA3, IL-12 DNA, IL-12 플라스미드, IL-12/GMCSF 플라스미드 (Sykes), IL-2/pcDNA3, IL-2/Ig 플라스미드, IL-2/Ig 단백질, IL-4, IL-4/pcDNA3, 이미퀴모드™, ImmTher™, 공동자극성 분자에 대한 항체를 함유한 이뮤노리포좀, 인터페론-γ, 인터루킨-1β, 인터루킨-12, 인터루킨-2, 인터루킨-7, ISCOM(s)™, Iscoprep 7.0.3™, 키홀 림펫 헤모시아닌, 지질-기반의 보강제, 리포좀, 록소리빈, LT(R192G), LT-OA 또는 LT 경구 보강제, LT-R192G, LTK63, LTK72, MF59, MONTANIDE ISA 51, MONTANIDE ISA 720, MPL.TM., MPL-SE, MTP-PE, MTP-PE 리포좀, 무라메티드 (Murametide), 무라팔미틴 (Murapalmitine), NAGO, nCT 네이티브 콜레라 독소, 비-이온성 계면활성제 소낭, 콜레라 독소의 무독성 돌연변이 E112K mCT-E112K, p-하이드록시벤조퀸산 메틸 에스테르, pCIL-10, pCIL12, pCMVmCAT1, pCMVN, 펩토머-NP, Pleuran, PLG, PLGA, PGA, 및 PLA, Pluronic L121, PMMA, PODDS™, Poly rA: Poly rU, 폴리소르베이트 80, 단백질 코크리트 (Cochleate), QS-21, Quadri A 사포닌, Quil-A, Rehydragel HPA, Rehydragel LV, RIBI, 리비라이크 보강제 시스템 (Ribilike adjuvant system) (MPL, TMD, CWS), S-28463, SAF-1, Sclavo 펩타이드, Sendai 프로테오리포좀, Sendai-함유 지질 매트릭스, Span 85, Specol, 스쿠알란 1, 스쿠알렌 2, 스테아릴 티로신, 파상풍 톡소이드 (TT), 테라미드™, 트레오닐 무라밀 다이펩타이드 (TMDP), Ty 입자 및 월터 리드 (Walter Reed) 리포좀 등이 있다. 보강제의 선택은 치료할 개체에 따라 결정된다. 바람직하게는, 약제학적으로 허용가능한 보강제를 이용한다.
제8 측면에서, 본 발명은 필요한 개체에 본 발명의 임의 구현예에 따른 폴리펩타이드, 나노입자, 조성물, 핵산, 약학적 조성물 또는 백신 ("면역원성 조성물"로 지칭됨)을 감염을 치료하거나 또는 감염의 진행을 제한하는데 유효한 양으로 투여하는 것을 포함하는, SARS-CoV-2 감염을 치료하거나 또는 감염의 진행을 제한하는 방법을 제공한다. 개체는, 비-제한적으로, 인간 개체 등의 임의의 적절한 포유류 개체일 수 있다.
본 방법이 SARS-CoV-2 감염의 제한을 포함하는 경우, 면역원성 조성물은 감염된 것으로 확인되지 않지만 SARS-CoV-2 노출 위험이 있을 수 있는 개체에게 예방학적으로 투여된다. 본원에서, "진행 제한"은 비-제한적으로 다음 중 한가지 이상을 달성하는 것을 포함한다: (a) 개체에서 SARS-CoV-2에 대한 면역 반응 (항체 및/또는 세포-기반의 면역 반응)의 발현; (b) 개체에서 SARS-CoV-2에 대한 중화 항체의 생성; (b) SARS-CoV-2에 노출된 후 개체에서 SARS-CoV-2 역가의 증가 제한; 및/또는 (c) 감염 후 SARS-CoV-2 증상의 진행 제한 또는 방지. SARS-CoV-2 감염에 대한 예시적인 증상으로는, 비-제한적으로, 발열, 피로, 기침, 숨가쁨, 가슴 압박 및/또는 통증, 후각 상실 또는 감소, 미각 상실 또는 감소, 및 호흡기 관련 문제, 비-제한적인 예로, 폐렴, 기관지염, 중증 급성 호흡기 증후군 (SARS), 및 상기도 및 하기도 감염을 포함한다.
일 구현예에서, 본 방법은 SARS-CoV-2로 감염된 것으로 확인되지 않은 개체에서 면역 반응을 유발하며, 면역 반응은 SARS-CoV-2 감염의 진행 또는 증상의 진행을 제한하는 역할을 한다. 일 구현예에서, 면역 반응은 SARS-CoV-2에 대항하는 중화 항체의 생성을 포함한다. 예시적인 이러한 구현예에서, 면역 반응은 SARS-CoV-2 스파이크 단백질 항체-특이적인 반응의 생성을 포함하며, 기하 평균 역가는 적어도 1 x 105이다. 추가적인 구현예에서, 면역 반응은 여러가지 항원성 에피토프들에 대항하는 항체의 생성을 포함한다.
본원에서, "유효량"은 SARS-CoV-2 감염을 치료 및/또는 제한하는데 효과적인 면역원성 조성물의 양을 의미한다. 본원의 임의의 구현예에 따른 폴리펩타이드, 나노입자, 조성물, 핵산, 약학적 조성물 또는 백신은 전형적으로 전술한 바와 같이 약학적 조성물로 제형화되며, 경구, 비경구, 흡입 분무, 직장 또는 국소 등의 임의의 경로를 통해 통상적인 약제학적으로 허용가능한 담체, 보강제 및 비히클을 함유한 투약 단위 제형으로 투여할 수 있다. 본원에서, 용어 비경구는 피하, 정맥내, 동맥내, 근육내, 흉골내, 힘줄내, 척수내, 두개강내, 흉강내, 주입 기법 또는 복막내를 포함한다. 폴리펩타이드 조성물은 또한 미소구, 리포좀, 면역-자극 복합체 (ISCOM), 또는 적절한 조직 (예, 혈액)으로 도입되는 기타 미세입자 전달 시스템 또는 지속 방출형 제형으로 투여할 수 있다. 투여량 용법은 최적의 원하는 반응 (예를 들어, 치료학적 또는 예방학적 반응)을 제공하도록 조정될 수 있다. 적절한 투여량 범위는 예를 들어 폴리펩타이드 또는 이의 나노입자 0.1 ㎍/체중 kg 내지 100 mg/체중 kg일 수 있다. 조성물은 단일 볼루스로 전달되거나, 또는 주치의에 의해 결정되는 바에 따라 1번 보다 더 많은 횟수 (예를 들어, 2, 3, 4, 5 또는 그 이상)로 투여할 수 있다.
일 구현예에서, 투여는 면역원성 조성물의 제1 용량 및 제2 용량의 투여를 포함하며, 제2 용량은 제1 용량의 투여 후 약 2주 내지 약 12주, 또는 약 4주 내지 약 12주에 투여된다. 다양한 추가적인 구현예들에서, 제2 용량은 제1 용량 투여 후 약 2주, 3주, 4주, 5주, 6주, 7주, 8주, 9주, 10주, 11주 또는 12주 경과 시점에 투여한다. 다른 구현예에서, 3종의 용량을 투여할 수 있으며, 제1 용량 투여 후 약 1주, 2주, 3주, 4주, 5주, 6주, 7주, 8주, 9주, 10주, 11주 또는 12주 경과시 제2 용량을 투여하고 제2 용량 투여 후 약 1주, 2주, 3주, 4주, 5주, 6주, 7주, 8주, 9주, 10주, 11주 또는 12주 경과시 제3 용량을 투여한다.
감작-부스트 투여 (prime-boost dosing)에 대한 다양한 다른 구현예들에서, 투여는 하기를 포함한다:
(a) 서열번호 125-137의 아미노산 서열에 대해 적어도 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100%의 아미노산 서열 동일성을 가진 아미노산 서열을 암호화하는 DNA, mRNA 또는 아데노바이러스 벡터 백신을, 감작 용량으로 개체에 투여; 및
(b) 개체에, 본원에 기술된 임의의 구현예 또는 구현예들의 조합에 따른 폴리펩타이드, 나노입자, 조성물, 핵산, 약학적 조성물 또는 백신을 부스트 용량으로 투여.
대안적인 구현예에서, 투여는 하기를 포함한다:
(a) 개체에 본원에 기술된 임의의 구현예 또는 구현예들의 조합을 감작 용량으로 투여; 및
(b) 개체에, 서열번호 125-137의 아미노산 서열에 대해 적어도 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100%의 아미노산 서열 동일성을 가진 아미노산 서열을 암호화하는 DNA, mRNA 또는 아데노바이러스 벡터 백신을, 부스트 용량으로 투여.
이들 구현예들 중 어느 하나에서, 임의의 적절한 DNA, mRNA 또는 아데노바이러스 벡터 백신은, 비-제한적으로, 개발될 백신뿐 아니라 Moderna, Pfizer/BioNTech, Johnson & Johnson 등으로부터 입수가능한 것을 비롯하여, 본 발명의 면역원성 조성물과 병행하여, 사용할 수 있다.
본 방법에 대한 다른 구현예에서, 개체는 비-제한적으로 SARS-CoV-2 등의 중증 급성 호흡기 (SARS) 바이러스로 감염되며, 투여는 개체에서 SARS 바이러스 감염을 치료하는 면역 반응을 개체에서 SARS 바이러스에 대항하여 유발한다. 방법이 SARS-CoV-2 감염의 치료를 포함하는 경우, 면역원성 조성물은 이미 SARS-CoV-2로 감염된 개체에, 및/또는 SARS-CoV-2로 감염되었을 가능성이 있음을 의미하는 (전술한) 증상을 앓고 있는 개체에 투여한다.
본원에서, "치료한다" 또는 "치료하는"은 다음 중 하나 이상을 달성하는 것을 포함하지만, 이들로 제한되는 것은 아니다: (a) 개체에서 SARS-CoV-2 역가 감소; (b) 개체에서 SARS-CoV-2 역가 증가의 제한; (c) SARS-CoV-2 증상의 중증도 저하; (d) 감염 후 SARS-CoV-2 증상의 진행 제한 또는 방지; (e) SARS-CoV-2 증상의 악화 저해; (f) 이미 SARS-CoV-2 감염 증상을 가진 개체에서 SARS-CoV-2 증상의 재발 제한 또는 방지; 및/또는 (e) 생존.
본 발명은 본 발명의 나노입자 및 조성물을 제조하는데 이용할 수 있는 키트를 추가로 제공한다. 일 구현예에서, 키트는 하기를 포함한다:
(a) 제1 측면에서와 같이, 본 발명에 개시된 임의 구현예 또는 구현예들의 조합에 따른 폴리펩타이드; 및
(b) 서열번호 152-159로 이루어진 군으로부터 선택되는 아미노산 서열에 대해 적어도 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100%의 동일한 아미노산 서열을 포함하는 제1 단백질로서, 괄호 안 서열이 선택으로, 존재하거나 또는 존재하지 않을 수 있는, 제1 단백질.
일 구현예에서, 폴리펩타이드는 서열번호 1 또는 5의 아미노산 서열을 포함하며, 제1 단백질은 서열번호 155의 아미노산 서열을 포함한다.
다른 구현예에서, 키트는 하기를 포함한다:
(a) 제1 측면에서와 같이 본원에 개시된 임의 구현예 또는 구현예들의 조합에 따른 폴리펩타이드를 암호화하는 핵산; 및
(b) 서열번호 152-159로 이루어진 군으로부터 선택되는 아미노산 서열에 대해 적어도 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100%의 동일한 아미노산 서열을 포함하는 제1 단백질을 암호화하는 핵산으로서, 괄호 안 서열이 선택적으로, 존재하거나 또는 존재하지 않을 수 있는, 핵산.
일 구현예에서, 폴리펩타이드는 서열번호 1 또는 5의 아미노산 서열을 포함하며, 제1 단백질은 서열번호 155의 아미노산 서열을 포함한다.
추가적인 구현예에서, 키트는 하기를 포함한다:
(a) 적절한 조절 서열에 작동가능하게 연결된, 제1 측면에서와 같이 본원에 개시된 임의 구현예 또는 구현예들의 조합에 따른 폴리펩타이드를 암호화하는 핵산을 포함하는, 발현 벡터; 및
(b) 적절한 조절 서열에 작동가능하게 연결된, 서열번호 152-159로 이루어진 군으로부터 선택되는 아미노산 서열에 대해 적어도 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100%의 동일한 아미노산 서열을 포함하는 제1 단백질을 암호화하는 핵산을 포함하는 발현 벡터로서, 괄호 안 서열이 선택적이며, 존재하거나 또는 존재하지 않을 수 있는, 발현 벡터.
일 구현예에서, 폴리펩타이드는 서열번호 1 또는 5의 아미노산 서열을 포함하며, 제1 단백질은 서열번호 155의 아미노산 서열을 포함한다.
다른 구현예에서, 키트는 하기를 포함한다:
(a) 발현 벡터를 포함하는 세포로서, 발현 벡터가 적절한 조절 서열에 작동가능하게 연결된, 제1 측면에서와 같이 본원에 개시된 임의 구현예 또는 구현예들의 조합에 따른 폴리펩타이드를 암호화하는 핵산을 포함하는, 세포; 및
(b) 발현 벡터를 포함하는 세포로서, 발현 벡터가 적절한 조절 서열에 작동가능하게 연결된, 서열번호 152-159로 이루어진 군으로부터 선택되는 아미노산 서열에 대해 적어도 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100%의 동일한 아미노산 서열을 포함하는 제1 단백질을 암호화하는 핵산을 포함하며, 괄호 안 서열이 선택적이며, 존재하거나 또는 존재하지 않을 수 있는, 세포.
일 구현예에서, 폴리펩타이드는 서열번호 1 또는 5의 아미노산 서열을 포함하며, 제1 단백질은 서열번호 155의 아미노산 서열을 포함한다.
실시예
SARS-CoV-2에 대해 설계된 단백질 나노입자 백신에 의한 강력한 중화 항체 반응의 유발
개요
현재 진행 중인 SARS-CoV-2 대유행을 중단시키기 위해, 안전하고, 효과적이며, 확장가능한 백신이 시급히 요구되고 있다. 본원에서, 본 발명자들은 마우스에서 SARS-CoV-2에 대항해 강력한 보호성 항체 반응을 유발하는 자기-조립성 단백질 나노입자 면역원에 대한 구조-기반 설계를 기술한다. 나노입자 백신은 고 면역원성 어레이에서 SARS-CoV-2 스파이크 (S) 당단백질 수용체-결합 도메인 (RBD) 카피를 60개 나열하며, 5배 이상 낮은 용량에도 불구하고 융합 전-안정화된 S 엑토도메인 삼량체보다 거의 10배 높은 중화 항체 역가를 유도한다. 나노입자 면역원에 의해 유발되는 항체는 RBD 상의 여러가지 개개 에피토프들을 표적화하므로, 탈출 돌연변이에 쉽게 취약하지 않고 회복기 인간 혈청보다 현저하게 낮은 결합:중화 비율을 나타내어 백신-관련 증가된 호흡 질환의 위험성을 최소화할 수 있음을, 시사해준다. 단백질 구성성분 및 조립된 나노입자의, 특히 SARS-CoV-2 융합 전-안정화된 S 삼량체와 비교해, 높은 수율 및 안정성은, 나노입자 백신의 제조를 상당히 확장가능함을, 의미한다.
SARS-CoV-2 RBD 나노입자 면역원의 설계, 시험관내 조립 및 특징 규명
강력한 중화 Ab 반응을 유도하는 백신 후보물질을 설계하기 위해, SARS-CoV-2 S 당단백질의 RBD에 집중하였다 (도 1A-B). 이 작은 단량체 항원의 제한적인 면역원성을 해결하기 위해, 2-성분 단백질 나노입자 I53-50의 외표면에 RBD를 다가로 나열하였다. I53-50은 삼량제 (I53-50A) 및 오량체 (I53-50B) 구성성분들 (모든 아미노산 서열은 표 3에 제공됨)로부터 20면체 대칭성을 가진 28 nm, 120-서브유닛 복합체로서 전산 시스템을 통해 설계하였다. 나노입자는 독립적으로 발현 및 정제한 I53-50A와 I53-50B를 단순히 혼합함으로써 시험관내에서 조립할 수 있다. RBD (잔기 328-531)는, 나노입자 표면으로부터 연장되는 항원을 유연하게 제시할 수 있도록, 글리신 및 세린 잔기를 8, 12 또는 16개 포함하는 링커를 이용해 I53-50A에 유전자 융합하였다 (이하, RBD-8GS-50A, RBD-12GS-50A 또는 RBD-16GS-I53-50A로 지칭됨)(도 1C). RBD-I53-50A 구조체들 모두 바이러스 항원의 적절한 접힘 및 당화를 구현하기 위해 포유류 (Expi293F) 세포를 이용해 재조합 방식으로 발현시켰다. 정제한 RBD-I53-50A 단백질의 처음 수율 (Expi293F 세포 L 당 정제 단백질 ~30 mg)은 융합 전-안정화된 S-2P 삼량체 (~1.5 mg/L)보다 ~20배 높았으며 (Kirchdoerfer et al., 2018; Pallesen et al., 2017; Walls et al., 2020; Wrapp et al., 2020), 프로모터 최적화 이후에는 ~60 mg/L로 상승하였다. RBD-I53-50A 단백질을 E. coli에서 정제한 오량체 I53-50B와 ~1:1 몰비 (서브유닛:서브유닛)로 혼합해, 나노입자 조립에 착수하였다 (도 1D).
표 3. 본 실험에 사용된 단백질의 아미노산 서열들 (도 1-6) 참조
>RBD-8GS-I53-50A
MGILPSPGMPALLSLVSLLSVLLMGCVAETGTRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTGGSGGSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATEGGSHHHHHHHH (서열번호 14)
>RBD-12GS-I53-50A
MGILPSPGMPALLSLVSLLSVLLMGCVAETGTRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTGSGSGGSGGSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATEGGSHHHHHHHH (서열번호 22)
>RBD-16GS-I53-50A
MGILPSPGMPALLSLVSLLSVLLMGCVAETGTRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTGGSGGSGSGGSGGSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATEGGSHHHHHHHH (서열번호 2)
>단량체 SARS-CoV-2 RBD
MGILPSPGMPALLSLVSLLSVLLMGCVAETGTRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTHHHHHHHH (서열번호 160)
>SARS-CoV-2 S-2P 삼량체
MGILPSPGMPALLSLVSLLSVLLMGCVAETGTQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPSGAGSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKGSGRENLYFQGGGGSGYIPEAPRDGQAYVRKDGEWVLLSTFLGHHHHHHHH(서열번호 161)
>hACE2(R518G)-Fc
MARAWIFFLLCLAGRALASTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWSAFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDNPQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYEDYGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYISPIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVSVGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHHEMGHIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKSIGLLSPDFQEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETYCDPASLFHVSNDYSFIRYYTGTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNMLRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYADPLVPRGSGGGGDPEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK(서열번호 162)
>mACE2-Fc
MPMGSLQPLATLYLLGMLVASVLAQSTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGEKWSAFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPNNPQECLLLDPGLNEIMEKSLDYNERLWAWEGWRSEVGKQLRPLYEEYVVLKNEMARANHYKDYGDYWRGNYEVNGVDGYDYNRDQLIEDVERTFEEIKPLYEHLHAYVRAKLMNAYPSYISPTGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVNQAWNAQRIFKEAEKFFVSVGLPNMTQGFWENSMLTDPGNVQKVVCHPTAWDLGKGDFRIIMCTKVTMDDFLTAHHEMGHIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKSIGLLSPDFQEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETYCDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLLNMLKLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYADQSIKVRISLKSALGDKAYEWNDNEMYLFRSSVAYAMRTYFLEIKHQTILFGEEDVRVADLKPRISFNFYVTAPKNVSDIIPRTEVEEAIRISRSRINDAFRLNDNSLEFLGIQTTLAPPYQSPVTDPLVPRGSGGGGDPEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK(서열번호 163)
>RBD-8GS-I53-50A
MGILPSPGMPALLSLVSLLSVLLMGCVAETGTRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTGGSGGSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATEGGSHHHHHHHH
>RBD-12GS-I53-50A
MGILPSPGMPALLSLVSLLSVLLMGCVAETGTRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTGSGSGGSGGSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATEGGSHHHHHHHH
>RBD-16GS-I53-50A
MGILPSPGMPALLSLVSLLSVLLMGCVAETGTRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTGGSGGSGSGGSGGSGSEKAAKAEEAARKMEELFKKHKIVAVLRANSVEEAIEKAVAVFAGGVHLIEITFTVPDADTVIKALSVLKEKGAIIGAGTVTSVEQARKAVESGAEFIVSPHLDEEISQFAKEKGVFYMPGVMTPTELVKAMKLGHTILKLFPGEVVGPQFVKAMKGPFPNVKFVPTGGVNLDNVAEWFKAGVLAVGVGSALVKGTPDEVREKAKAFVEKIRGATEGGSHHHHHHHH
>단량체 SRS-CoV-2 RBD
MGILPSPGMPALLSLVSLLSVLLMGCVAETGTRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTHHHHHHHH
>SARS-CoV-2 S-2P 삼량체
MGILPSPGMPALLSLVSLLSVLLMGCVAETGTQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPSGAGSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKGSGRENLYFQGGGGSGYIPEAPRDGQAYVRKDGEWVLLSTFLGHHHHHHHH
>hACE2(R518G)-Fc
MARAWIFFLLCLAGRALASTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWSAFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDNPQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYEDYGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYISPIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVSVGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHHEMGHIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKSIGLLSPDFQEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETYCDPASLFHVSNDYSFIRYYTGTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNMLRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYADPLVPRGSGGGGDPEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
>mACE2-Fc
MPMGSLQPLATLYLLGMLVASVLAQSTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGEKWSAFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPNNPQECLLLDPGLNEIMEKSLDYNERLWAWEGWRSEVGKQLRPLYEEYVVLKNEMARANHYKDYGDYWRGNYEVNGVDGYDYNRDQLIEDVERTFEEIKPLYEHLHAYVRAKLMNAYPSYISPTGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVNQAWNAQRIFKEAEKFFVSVGLPNMTQGFWENSMLTDPGNVQKVVCHPTAWDLGKGDFRIIMCTKVTMDDFLTAHHEMGHIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKSIGLLSPDFQEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETYCDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLLNMLKLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYADQSIKVRISLKSALGDKAYEWNDNEMYLFRSSVAYAMRTYFLEIKHQTILFGEEDVRVADLKPRISFNFYVTAPKNVSDIIPRTEVEEAIRISRSRINDAFRLNDNSLEFLGIQTTLAPPYQSPVTDPLVPRGSGGGGDPEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
SARS-CoV-2 RBD-I53-50 나노입자의 크기 배제 크로마토그래피 (SEC)에서, 표적 20면체 어셈블리에 해당하는 우세한 피크와 남아있는 비-조립 RBD-I53-50A 구성성분들을 포함하는 더 작은 피크가 관찰되었다 (도 7A 및 7B). 동적 광 산란 (DLS) 및 음성 염색 전자 현미경 검경 (nsEM)에서, 냉동/해동 수행 전 및 수행 후 모두 다양한 RBD-I53-50 나노입자들의 균질성과 단분산성이 검증되었다 (도 1E, 1F 및 7C). 냉동/해동 전, RBD-8GS-I53-50, RBD-12GS-I53-50 및 RBD-16GS-I53-50에서, DLS에 의해 측정한 평균 유체역학적 직경 및 다분산성 %는 각각 38.5 (27%), 37 (21%) 및 41 (27%) nm였으며, 이와 비교해 비-변형 I53-50 나노입자는 30 (22%) nm이었다. 수소/중수소-교환 질량 분광 측정에서, 삼량체 RBD-8GS-I53-50A 구성성분 상의 RBD 나열이 항원의 입체 형태 및 수종의 개별 항체 에피토프들의 구조적 순서를 보존하는 것으로, 검증되었다 (도 1G 및 7D). 마지막으로, 모두 3종의 RBD-I53-50A 구성성분들이 SARS-CoV-2 S-2P 엑토도메인 삼량체와 유사하게 N331 및 N343 위치에서 N-당화되었는지를 확인하기 위해 글리코프로테오믹스를 이용하였으며 (Watanabe et al., 2020), 재차, 나열된 항원들이 본래의 항원 특성을 유지하고 있는 것으로 나타났다 (도 1H 및 7E).
표 4. SARS-CoV-2 RBD-I53-50A 구성성분의 항원 특징 규명
항원 결합제 kon (M-1 s-1) koff (s-1) KD (nM)
SARS-CoV-2 RBD hACE2 7x104 ± 5x102 5x10-3 ± 1x10-5 69 ± 0.5
CR3022 Fab 2x105 ± 2x103 9x10-3 ± 3x10-5 45 ± 0.5
RBD-8GS-I53-50A hACE2 6x104 ± 4x102 4x10-3 ± 1x10-5 70 ± 0.5
CR3022 Fab 2x105 ± 1x103 1x10-2 ± 3x10-5 57 ± 0.4
RBD-12GS-I53-50A hACE2 6x104 ± 4x102 5x10-3 ± 1x10-5 78 ± 0.5
CR3022 Fab 2x105 ± 2x103 9x10-3 ± 2x10-5 42 ± 0.4
RBD-16GS-I53-50A hACE2 6x104 ± 4x102 4x10-2 ± 1x10-5 66 ± 0.4
CR3022 Fab 2x105 ± 1x103 1x10-2 ± 2x10-5 56 ± 0.4
각각의 실험은 2번 이상 수행하였으며, 열거한 값과 피팅 오차는 대표적인 실험으로부터 파생한다. 대응되는 결합 곡선 및 피팅을 도 8에 나타낸다.
SARS-CoV-2 RBD-I53-50 나노입자 구성성분 및 면역원의 항원 특징 규명
본 발명자들은 재조합 인간 ACE2 엑도도메인과 2개의 S-특이적인 mAb (CR3022 및 S309)를 이용해, I53-50A에 융합시 RBD의 항원성 뿐만 아니라 조립된 나노입자 면역원 상황에서 여러가지 RBD 에피토프들에 대한 접근성을 규명하였다. CR3022 및 S309는 둘다 SARS-CoV로 감염된 개체에서 분리하였으며, SARS-CoV-2 RBD와 교차-반응한다. CR3022는 RBD 개방시 접근가능해지지만, ACE2와 상호작용하는 RBD의 표면에 존재하는 수용체 결합 모티프 (RBM)와는 구분되는, RBD 내 보존된, 숨겨진 에피토프에 결합하는 약한 중화 Ab이다 (Huo et al., 2020; ter Meulen et al., 2006; Yuan et al., 2020). S309는 열린 및 닫힌 융합 전 S 입체구조 상태 둘다에서 접근가능한, 사베코바이러스 (sarbecoviruse)에 보존된 글리칸-함유 에티토프에 결합함으로써, SARS CoV와 SARS-CoV-2를 둘다 중화한다 (Pinto et al., 2020).
본 발명자들은 생물층 간섭 측정 (BLI)으로, 단량체 인간 ACE2 (hACE2) 엑도도메인 및 CR3022 Fab의 단량체 RBD에 대한 결합 친화성을 검증하였다. 고정된 RBD-I53-50A 융합 단백질에서 이들 물질의 평형 해리 상수 (KD)는 단량체 RBD에서 수득한 결과와 매우 일치하였다 (표 4 및 도 8). 이들 데이터는, RBD-I53-50A 융합 단백질이 본래의 입체 형태로 RBD를 나열함을, 추가적으로 검증해준다.
나노입자 면역원-유발성 Ab 반응의 정도 및 특성을 조밀한 다가 항원 어레이 설정에서 특이적인 에피토프의 접근성에 의해 조절할 수 있는지를 평가하기 위해, 고정된 이량체 마카크 ACE2 (mACE2-Fc), CR3022 및 S309 mAb에 대한 나노입자 면역원의 결합성을 측정하였으며, 후자의 것은 B 세포 활성화에 중심이 되는 B 세포 수용체 (BCR-항원 상호작용을 거의 모방한다. 이런 방식은 상호작용의 다가 특성으로 인해 KD 값을 계산할 수 없지만, 여러가지 나노입자 구조체에서 에피토프 접근성을 정성적으로 비교할 수 있다. 본 발명자들은 RBD 60개를 나열한 완전-결합가 나노입자를, 시험관내 조립의 다양성을 적용해 RBD 항원을 50% 결합가로 나열하는 (나노입자 당 RBD ~30개) 나노입자 면역원을 제조함으로써 덜 조밀한 항원 어레이와 비교하였다 (도 9). 이는, RBD-I53-50A와 융합된 항원이 없는 비-변형된 I53-50A를 동일 몰 비율로 혼합한 혼합물에 오량체 I53-50B를 첨가함으로써, 달성하였다. 본 발명자들은 RBD 나노입자들 모두 고정된 mACE2-Fc, CR3022 및 S309에 잘 결합함을 확인하였다 (도 2A). 결합가 50% 및 100%의 RBD-8GS-I53-50 나노입자 및 RBD-12GS-I53-50 나노입자들에서 일관된 경향은 없었지만, 결합가 100% RBD-16GS-I53-50 나노입자는 3가지 결합 물질 모두에서 최대 결합 신호를 나타내었다 (도 2B). RBD-16GS-I53-50 나노입자의 더 긴 링커가 ACE2, CR3022 및 S309에 의해 표적화되는 에피토프에 더 잘 접근가능한 이유일 수 있지만, 본 실험의 데이터가 다른 가능성 있는 해석을 배제할 수 있는 것은 아니다. 본 발명자들은, 중화 항체에 의해 표적화되는 여러가지 개별 에피토프들이 노출되어, 나노입자 외측에 제시된 RBD 항원 어레이 상황에서 결합하기 위해 접근가능해진 것으로, 결론지었다.
RBD 나노입자 면역원 및 S-2P 삼량체의 물리적 및 항원성 안정성
본 발명자들은 먼저 구아니딘 하이드로클로라이드 (GdnHCl)에서 화학적 변성을 이용해, RBD-I53-50A 융합 단백질 및 RBD-12GS-I53-50 나노입자 면역원의 안정성을 재조합 단량체 RBD 및 S-2P 엑토도메인 삼량체와 비교하였다 (도 3A). 0-6.5 M GdnHCl 중에 인큐베이션한 샘플은, 형광 방출 스펙트럼 결과, RBD-I53-50A 융합 단백질 3종 모두, 그리고 RBD-12GS-I53-50 나노입자가 4-5 M GdnHCl에서 적어도 일부 언-폴딩 (unfolding)으로 전이되고, S-2P 삼량체는 더 낮은 [GdnHCl], 즉 2-4 M에서 전이되는 것으로 드러났다. 단량체 RBD는 0-5 M GdnHCl에서 덜 협력적인 언폴딩 전이를 나타내었다. 이후, 본 발명자들은 일련의 분석법을 이용해, 3가지 온도, 즉 <-70℃, 2-8℃ 및 22-27℃에서 정제 후 4주간 물리적 및 항원 안정성을 확인하였다 (도 3B-E). 이전의 발표와 일관적으로, 단량체 RBD는 SDS-PAGE (도 10A), mACE2-Fc 및 CR3022 결합 (도 10B), 또는 미립자 산란의 척도인 320/280 nm에서의 UV/vis 흡광도 비 (도 10C)에 따르면, 외관상 거의 변화가 없는 것으로 나타나, 상당히 안정적인 것으로 입증되었다. S-2P 삼량체는 2-8℃에서 불안정하였으며, nsEM에 따르면 심지어 이른 시점에 명백한 언폴딩 신호를 나타내었다 (도 9D). 이는 언폴딩이 nsEM에 의해 명확해지고 UV/vis에서 일부 응집체가 확인되는 가장 늦은 시점 (28일)까지 그 구조가 22-27℃에서 상당히 양호하게 유지되었다 (도 10C). RBD-I53-50A 구성성분들 3종 모두 매우 안정적이었으며, 임의 시점에 임의 판독 값에 실질적인 변화가 없었다 (데이터 도시 안함). 마지막으로, RBD-12GS-I53-50 나노입자 역시 4주간의 실험 기간 중에 매우 안정적으로 단지 UV/vis 흡광도에만 변화가 있었는데, 22-27℃에서 7일 이후에 320 nm 부근에서 피크가 관찰되었다 (데이터 도시 안함). 전자 현미경 사진 및 DLS에 의하면, RBD-12GS-I53-50 나노입자 샘플들은 일관적으로 4주 동안 모든 온도들에서 단분산성을 가진 잘-형성된 나노입자를 나타내었다 (도 10D, 10E). 종합적으로, 이들 데이터는, RBD-I53-50A 구성성분 및 RBD-12GS-I53-50 나노입자가 S-2P 엑토도메인 삼량체보다 우수한 높은 물리적 및 항원성 안정성을 가진다는 것을, 보여준다.
RBD-I53-50 나노입자 면역원은 BALB/c 및 인간 면역 레퍼토리 마우스에서 강력한 중화 항체 반응을 유발한다.
본 발명자들은 각각 결합가 50% 또는 100%로 RBD를 나열하는 RBD-I53-50 나노입자 3종의 면역원성을, S-2P 엑토도메인 삼량체 및 단량체 RBD와, BALB/c 마우스에서 비교하였다. 마우스 10마리로 구성된 군에, 용해성 또는 미립자 형태로 SARS-CoV-2 항원 0.9 또는 5 ㎍이 함유된 AddaVax™M-보강제 첨가 제형을, 0주 및 3주에 근육내 주사하여 면역화하였다. 감작 후 3주차에, RBD 나노입자들 모두 견고한 S-특이적인 Ab 반응을 유발하였으며, 기하 평균 역수 1/2 최대 유효 농도 범위는 8x102 내지 1x104이었다 (도 4A). 이와는 대조적으로, 단량체 RBD와 저 용량의 S-2P 삼량체는 S-특이적인 Ab를 검출가능한 수준으로 유도하지 못하였으며, 고 용량의 S-2P 삼량체는 약한 반응을 유도하였다. 2차 면역화 후, RBD 나노입자 군들 모두에서 S-특이적인 Ab 역가의 증가가 관찰되었으며, 기하 평균 역가 (GMT)는 1x105 내지 2x106 범위였다 (도 4B). 이러한 S-특이적인 Ab 수준은 워싱턴 주의 COVID-19 인간 회복기 혈청 (HCS) 29종 패널 및 NIBSC의 벤치마크 20/130 COVID-19 혈장의 대부분 샘플들과 일치하거나 또는 이를 초과하였다 (도 4A-B, 표 5). S-2P 삼량체를 5 ㎍으로 2회 투여해 면역화한 결과 S-특이적인 Ab 반응은 RBD 나노입자와 비교해 ~1-2배 정도 약하였으며, 단량체 RBD는 2회 면역화 후 검출가능한 항원-특이적인 Ab를 유발하지 못하였다. 예상된 바와 같이, 본 발명자들은 I53-50 스캐폴드에 대해 Ab 반응을 검출하였으며, 그 정도가 모든 RBD 나노입자 군들에서 일정하였다 (도 11). 이들 데이터는 자기-조립 나노입자 스캐폴드 상에 RBD 다가 나열이 이의 면역원성을 극적으로 개선함을, 보여준다.
표 5. 환자 회복기 혈청의 공급원
　 입원 (N=4) 비-입원 (N=22) 총 (N=26)
나이 　 　 　
평균 (SD) 58.0 (15.1) 45.1 (17.2) 47.1 (17.2)
중앙값 [최소, 최대] 64.8 [35.5, 67.0] 43.6 [18.1, 76.0] 45.4 [18.1, 76.0]
성별 　 　 　
남성 1 (25.0%) 11 (50.0%) 12 (46.2%)
여성 3 (75.0%) 11 (50.0%) 14 (53.8%)
인종 　 　 　
아시아인 1 (25.0%) 2 (9.1%) 3 (11.5%)
흑인 또는 아프리카계 미국인 1 (25.0%) 0 (0%) 1 (3.8%)
백인 2 (50.0%) 20 (90.9%) 22 (84.6%)
히스패닉계 0 (0%) 1 (4.5%) 1 (3.8%)
보험 　 　 　
사보험 3 (75.0%) 17 (77.3%) 20 (76.9%)
공공보험 1 (25.0%) 5 (22.7%) 6 (23.1%)
주거 유형 　 　 　
주택/콘도/타운하우스 1 (25.0%) 5 (22.7%) 6 (23.1%)
아파트 3 (75.0%) 17 (77.3%) 20 (76.9%)
주거자 수 　 　 　
2명 1 (25.0%) 10 (45.5%) 11 (42.3%)
3명 1 (25.0%) 1 (4.5%) 2 (7.7%)
4명 0 (0%) 2 (9.1%) 2 (7.7%)
5명 0 (0%) 2 (9.1%) 2 (7.7%)
6명 이상 1 (25.0%) 2 (9.1%) 3 (11.5%)
자신만 주거 1 (25.0%) 5 (22.7%) 6 (23.1%)
흡연 　 　 　
비-흡연자 4 (100%) 19 (86.4%) 23 (88.5%)
담배 흡연 0 (0%) 3 (13.6%) 3 (11.5%)
전자 담배/증기 펜 사용자 0 (0%) 1 (4.5%) 1 (3.8%)
2019-2020 인플루엔자 백신 접종 (N=23) 2 (50.0%) 16 (72.7%) 18 (69.2%)
취업자 　 　 　
은퇴 1 (25.0%) 0 (0%) 1 (3.8%)
자영업자 1 (25.0%) 4 (18.2%) 5 (19.2%)
무직 0 (0%) 2 (9.1%) 2 (7.7%)
유급 공가, 해당 2 (50.0%) 12 (54.5%) 14 (53.8%)
무급 공가, 해당 0 (0%) 4 (18.2%) 4 (15.4%)
최고 수준의 의료 치료 제공 　 　 　
외래 환자 - 검사시에만 0 (0%) 15 (68.2%) 15 (57.7%)
외래 환자 - Saw 제공자** 0 (0%) 7 (31.8%) 7 (26.9%)
입원 환자 (일반병동) 2 (50.0%) 0 (0%) 2 (7.7%)
입원 환자 (ICU) 2 (50.0%) 0 (0%) 2 (7.7%)
동반질환* 　 　 　
동반질환 없음 1 (25.0%) 20 (90.9%) 21 (80.8%)
고혈압 2 (50.0%) 2 (9.1%) 4 (15.4%)
당뇨병 2 (50.0%) 0 (0%) 2 (7.7%)
심혈관 질환 1 (25.0%) 0 (0%) 1 (3.8%)
만성 신장 질환 1 (25.0%) 0 (0%) 1 (3.8%)
심혈관 질환 1 (25.0%) 0 (0%) 1 (3.8%)
HIV 1 (25.0%) 0 (0%) 1 (3.8%)
최고 수준의 호흡 보조 지원 　 　 　
없음 1 (25.0%) 22 (100%) 23 (88.5%)
비-침습적인 호흡기 (BiPAP) 1 (25.0%) 0 (0%) 1 (3.8%)
기계 호흡/삽관 2 (50.0%) 0 (0%) 2 (7.7%)
최근 30일간 다른 주로 여행 (N=23) 0 (0%) 4 (18.2%) 4 (15.4%)
증상* 　 　 　
발열감 3 (75.0%) 15 (68.2%) 18 (69.2%)
기침 4 (100%) 17 (77.3%) 21 (80.8%)
오한 또는 떨림 3 (75.0%) 15 (68.2%) 18 (69.2%)
발한 2 (50.0%) 14 (63.6%) 16 (61.5%)
목이 따갑거나 또는 목이 가렵거나/칼칼한 증상 0 (0%) 10 (45.5%) 10 (38.5%)
구역질 또는 구토 1 (25.0%) 3 (13.6%) 4 (15.4%)
콧물 또는 코막힘 1 (25.0%) 13 (59.1%) 14 (53.8%)
근육통 또는 몸살 2 (50.0%) 15 (68.2%) 17 (65.4%)
호흡 곤란 증가 3 (75.0%) 5 (22.7%) 8 (30.8%)
피로 2 (50.0%) 17 (77.3%) 19 (73.1%)
설사 2 (50.0%) 6 (27.3%) 8 (30.8%)
발진 0 (0%) 1 (4.5%) 1 (3.8%)
귀 통증 또는 귀 분비물 0 (0%) 1 (4.5%) 1 (3.8%)
미각 또는 후각 상실 0 (0%) 7 (31.8%) 7 (26.9%)
* 범주는 상호 배타적인 것은 아님.
** 1차 진료 의사, 긴급 치료, 응급실 포함
본 발명자들은 재정렬되지 않은 인간 항체 가변부 및 불변부 생식계열 레퍼토리에 대해 형질전환성인 Kymab proprietary IntelliSelect™ 형질전환 마우스 플랫폼 ('Darwin'으로 알려져 있음)을 사용해 RBD 나노입자 면역원들에 대한 잠재적인 인간 항체 반응의 원형을 확인하였다. (Lee et al., 2014)에 언급된 키메라 항체 유전자 좌를 가진 이전의 마우스와는 대조적으로, 본 실험의 마우스는 완전한 인간 카파 경쇄 Ab를 발현하도록 조작되었다는 점에서 차이가 있다. Darwin 마우스 5마리로 구성된 군들에 S-2P 삼량체, 100% RBD-12GS-I53-50 나노입자 또는 100% RBD-16GS-I53-50 나노입자를 항원 용량 0.9 ㎍ (나노입자 단독) 또는 5 ㎍으로 근육내 주사하여 면역화하였다 (도 4C). RBD 나노입자로 면역화된 군들 모두 감작 후 S-특이적인 Ab 반응 (EC50 2x103-1x104)을 나타내었으며, 이는 3주차에 2차 면역화 후 실질적으로 강화되었다 (EC50 4x105 내지 8x105)(도 4C 및 4D). 이 동물 모델에서, S-2P 삼량체는 각각의 면역화 후 RBD 나노입자와 비슷한 수준으로 S-특이적인 Ab를 생성하였다.
다음으로, 본 발명자들은 슈도바이러스 및 살아있는 바이러스 중화 분석 2가지를 이용해 각 면역원에 의해 발생되는 중화 활성을 분석하였다. BALB/c 마우스에서, RBD 나노입자 면역원들 모두 1회 면역화 후 혈청 중화 Ab를 유발하였으며, 역수 1/2 최대 저해 희석 (IC50)은 슈도바이러스에서는 1x102 내지 5x102 (GMT), 살아있는 바이러스 중화 분석에서는 3x103 내지 7x103 범위였다 (도 5A 및 5C). S-특이적인 Ab 데이터와 동일하게, 저 용량 또는 고 용량의 RBD-8GS-I53-50 나노입자, RBD-12GS-I53-50 나노입자 또는 RBD-16GS-I53-50 나노입자 간에, 50% (슈도바이러스 중화 단독) 또는 100% 결합가에서, 슈도바이러스 또는 살아있는 바이러스 중화에 유의한 차이는 없었다. 결합가 100%의 RBD 나노입자 군 3종 모두 GMT가 슈도바이러스 중화 분석에서 검사한 29 HCS 패널의 결과와 일치하거나 또는 초과하였다 (도 5A). 단량체 RBD 또는 S-2P 삼량체를 이용한 면역화는 1회 면역화 후 중화 Ab를 유발하지 못하였다 (도 5A 및 5C). BALB/c 마우스에서와 같이, Darwin 마우스에서 고 용량 및 저 용량의 RBD-I53-50 나노입자는 둘다 1회 면역화 후 HCS (IC50 1x102)에 상응하는 수준으로 슈도바이러스 중화 Ab 역가를 유도 (IC50 8x101 내지 2.5x102)한 반면, S-2P 삼량체 5 ㎍은 유사한 수준의 전체 S-특이적인 Ab를 유도하였음에도 불구하고 중화 Ab는 검출가능한 수준으로 유도하지 못하였다 (도 5E).
이들 2종의 마우스 모델에서, RBD-I53-50 나노입자를 이용한 2차 면역화는 중화 Ab 역가를 크게 상승시켰다. BALB/c 마우스에서, 슈도바이러스 중화 GMT는 2x103 내지 3x104에 도달해 HCS를 1-2배 초과하였으며, 살아있는 바이러스 중화 역가는 2x104 내지 3x104에 도달하였다 (도 5B 및 5D). S-2P 삼량체 5 ㎍을 이용한 2차 면역화 역시 중화 활성을 강하게 강화하였지만, 슈도바이러스 및 살아있는 바이러스 중화 (각각 GMT 3x102 및 6x103)는 RBD 나노입자로 면역화한 동물의 혈청에서보다 여전히 낮았다. S-2P 삼량체와 RBD 나노입자 간의 증가 수준은 슈도바이러스 및 살아있는 바이러스 중화 분석에서 각각 7-90배 및 4-9배 범위였다. 0.9 ㎍ 용량의 S-2P 삼량체 및 2가지 용량의 단량체 RBD는 2회 면역화 후 검출가능한 중화를 유발하지 못하였다. Darwin 마우스에서 2차 면역화 후 슈도바이러스 중화에서 비슷한 상승이 관찰되었지만, 역가가 BALB/c 마우스에서보다 전체적으로 낮았다 (도 5F).
이러한 데이터로부터 몇가지 결론을 도출할 수 있다. 첫째, RBD 나노입자는 2가지 마우스 모델에서, 융합 전-안정화된 S-2P 삼량체 및 2회 투여 후 인간 감염에 의해 유발되는 수준을 능가하는, 강력한 중화 Ab 반응을 유발한다. 둘째, 링커의 길이와 항원 결합가는 RBD 나노입자의 전체적인 면역원성에 실질적으로 영향을 미치지 않지만, RBD-16GS-I53-50이 더 짧은 링커를 가진 나노입자보다 면역원성이 더 높을 수 있음을 시사하는 경향이 있다. 이러한 발견 사실은, 여러가지 에피토프들이 모든 RBD 나노입자 면역원에서 온전하고 접근가능하다는 것을 보여주는, 도 2 및 표 4에 제시된 항원 및 접근성 데이터와 일치한다. 마지막으로, 각 나노입자 면역원이 0.9 및 5 ㎍ 용량 둘다에서 비슷한 중화 Ab 역가를 유도한다는 점은, I53-50 나노입자 상의 RBD 제시가 백신 제조 및 유통에서 중요한 고려요소인 용량 감소를 가능케 한다는 점을 시사해준다.
AddaVax™ 단독, 단량체 RBD, S-2P 삼량체, RBD-8GS-I53-50 나노입자 또는 RBD-12GS-I53-50 나노입자로 면역화한 마우스 8마리에, 마우스-적응된 SARS-CoV-2 바이러스 (SARS-CoV-2 MA)를 부스트 후 7주차에 기회 감염시켜, 이들 면역원이 바이러스 복제로부터 보호를 제공하는지를 확인하였다. RBD-8GS-I53-50 나노입자 및 RBD-12GS-I53-50 나노입자는 마우스 폐 및 비갑개에서 검출가능한 SARS-CoV-2 MA 복제를 완전히 방지하였다 (도 5G-H). 단량체 RBD, 0.9 ㎍ S-2P 삼량체 및 보강제 대조군을 이용한 면역화는 SARS-CoV-2 MA 복제를 방지하지 못하였다. 이들 결과는 RBD 나노입자가 어느 한가지 용량 또는 결합가에서 강력한 anti-SARS-CoV-2 Ab 반응을 유도함을 보여주는 슈도바이러스 및 살아있는 바이러스 중화 데이터를 반영해준다.
RBD 나노입자 백신은 마우스 및 인간을 제외한 영장류에서 여러가지 에피토프를 표적화하는 항체와 견고한 B 세포 반응을 일으킨다.
배중심 (GC) 반응은 항구적인 B 세포 기억을 형성하는데 있어 핵심적인 과정으로, 그 결과 친화성-성숙된, 클래스-스위치 기억 B 세포 및 장기 생존 형질세포가 만들어진다. 이에, 본 발명자들은 단량체 RBD, S-2P 삼량체, RBD-8GS-I53-50 나노입자, RBD-12GS-I53-50 나노입자 및 RBD-16GS-I53-50 나노입자로 면역화한 마우스에서 항원-특이적인 GC B 세포 반응을 조사하였다. RBD-특이적인 B 세포의 양 및 표현형을 면역화 후 11일차에 분석해, GC 전구체와 B 세포 (B220+CD3-CD138-CD38-GL7+)의 수준을 측정하였다 (도 12). RBD 나노입자로 면역화한 결과 RBD-특이적인 B 세포와 GC 전구체 및 B 세포이 증폭되었다 (도 6A-C). S-2P 삼량체의 경우, RBD-특이적인 B 세포와 GC 전구체 및 B 세포가 검출가능하였지만, 개수 및 빈도는 RBD 나노입자와 비교해 낮았으며, 단량체 RBD 구조체는 인지가능한 B 세포 반응을 유발하지 못하였다. 이러한 결과와 일관적으로, RBD 나노입자 3종 및 삼량체 S-2P를 이용한 면역화에서는, 기능성 GC 전구체 및 GC B 세포를 의미하는, CD38+/-GL7+ IgM+ 및 클래스-스위칭된 (swIg+) RBD-특이적인 B 세포가 등장하였다 (도 6D). RBD-나노입자로 면역화한 마우스와, 약한 수준이지만 S-2P 구조체로 면역화한 마우스에서, 견고한 GC B 세포 반응과 IgM+ 및 swIg+ RBD-특이적인 B 세포의 비율 증가는, 기억 B 세포와 장기 생존하는 형질 세포가 결과적으로 만들어지는 진행 중인 GC 반응과 일치한다. RBD 나노입자 백신에 의해 유발되는 체액성 반응의 항구성을 평가하기 위해, 본 발명자들은 부스트 후 20-24주차에 혈청 Ab 반응을 분석하였다. 결합 및 중화 역가의 정도는 모든 나노입자 군들에서 부스트 후 2주차의 수준과 비슷하였는데 (도 12B, C), 이는 설계된 면역원들이 강력할 뿐만 아니라 항구적인 중화 Ab를 유발한다는 것을 의미한다. 이는, 골수에서 S-2P-특이적인 Ab를 분비하는 세포의 수가 RBD-16GS-I53-50 나노입자로 면역화된 마우스에서 S-2P 삼량체와 비교해 ~3배 더 높았으므로, 장기 생존하는 형질세포의 유도가 나노입자 백신에 의해 개선된 것이, 일부 그 이유일 가능성이 있다 (도 12D).
본 발명자들은 S-2P, RBD-8GS-I53-50 나노입자, RBD-12GS-I53-50 나노입자 및 RBD-16GS-I53-50 나노입자에 의해 유발되는 중화 항체 및 나노입자 면역원에 의해 유발되는 Ab 반응의 정성적인 척도로서 HCS에 대한 결합율을 비교하였다. Kymab Darwin™ 마우스에서, 나노입자 백신은 S-2P-면역화 마우스보다 낮지 (양호하지)만 HCS보다는 높은 결합율을 나타내었다 (도 6E). BALB/c 마우스에서, RBD-12GS-I53-50 및 RBD-16GS-I53-50에 의해 유발되는 슈도바이러스 중화 역가에 대한 결합율은 S-2P 및 HCS와 비교해 명백하게 감소하였다 (도 6F). 이런 패턴은, 살아있는 바이러스 중화 역가를 이용해 계산하였을 때 계속적으로 나타났지만, 군들 간의 차이 정도는 살아있는 바이러스 중화 분석에서 수득된 높은 값으로 인해 더 작았다. 이들 결과는 RBD-12GS-I53-50 및 RBD-16GS-I53-50 나노입자 면역원에 의해 발생되는 Ab 반응이 S-2P 삼량체를 이용한 면역화로 수득되거나 또는 자연 감염 중에 획득되는 것보다 질적으로 더 우수하다는 것을 시사해주는데, 아마도 그 이유는 대부분의 중화 Ab들의 표적인 RBD 내 에피토프들에 초점을 맞추었기 때문이다.
본 발명자들은 백신 접종에 대한 면역 반응이 인간에서와 매우 비슷한 인간이 아닌 영장류 모델에서 나노입자 면역원을 이용한 면역화시 유발되는 Ab에 의해 인지되는 에피토프를 동정하고자 착수하였다. 피그테일 마카크에 RBD-12GS-I53-50 250 ㎍ (RBD 항원 88 ㎍)을 0주 및 4주에 접종하여 면역화하였으며, 8주에 수집한 혈청에서 S-특이적인 Ab가 높은 수준 (EC50 ~1x106)으로 존재한다는 것을 확인하였다. 다클론 Fab를 생산하고, SARS-CoV-2 RBD 상에서 중화 Ab에 의해 표적화되는 3종의 개별 부위들을 인지하는 hACE2, CR3022 및 S309와 함께 경쟁적인 BLI에 사용하기 위해 이를 정제하였다 (도 6G). 다클론 혈청은 각각의 해리 상수보다 높은 농도에서 hACE2, CR3022 Fab 및 S309 Fab의 결합을 용량-의존적인 방식으로 저해하였다 (도 6H-J). 이들 데이터는, 12GS-RBD-I53-50을 이용한 면역화가 수종의 비-중첩성 에피토프들을 표적화하는 Ab를 유발한다는 것을 의미하며, 특히 코로나바이러스는 인플루엔자 또는 인간 면역결핍 바이러스와 같은 바이러스와 비교해 빠르게 돌연변이되지 않기 때문에 탈출 돌연변이의 출현 및 선택 가능성을 제한할 것으로 예상된다 (Li et al., 2020; Smith et al., 2014).
고찰
여기서 본 발명자들은 2-성분 자기-조립성 SARS-CoV-2 RBD 나노입자 백신 후보물질이 여러가지 구분되는 RBD 에피토프들을 표적화하는 강력한 중화 Ab 반응을 유발한다는 것을 입증하였다. RBD 나노입자에 의해 유발되는 중화 Ab 반응이 융합 전-안정화된 엑토도메인 삼량체보다 더 높은 것은 매우 기대되는 부분이다. 본 발명의 데이터는, RBD-12GS-I53-50 및 RBD-16GS-I53-50이 S-특이적인 Ab를 거의 10배 높은 수준으로 유발하고, 보다 중요하게는 S-2P 엑토도메인 삼량체와 비교해 중화 활성이 거의 10배 높다는 것을, 보여준다. 이러한 효능 강화는 중량 기준으로 항원 용량이 5배 이상 낮은 용량으로 유지되므로, 나노입자 상의 제시가 용량을 절약하는 효과가 있다는 것을 시사해준다. 효능 강화 및 용량 절약 모두 SARS-CoV-2 대유행에 응답하기 위해 전례없이 많은 양의 백신을 제조하여야 하는 요구를 해결하는데 중요할 수 있다.
RBD는 단량체로서는 면역원성이 낮지만, 본 발명의 설계에서 다가로 제시될 경우 고 면역원성 백신의 토대를 형성할 수 있는 것으로, 본 발명의 데이터에 따라 확립되었다. RBD 나노입자를 이용한 면역화시 유발되는 예외적으로 낮은 결합:중화 비율은, I53-50 상에 RBD 제시가 중화 Ab에 의해 인지되는 에피토프에 대한 체액성 반응에 집중한다는 것을 시사해준다. 이런 점은, 결합 수준은 높지만 중화하지 않거나 또는 약하게 중화하는 Ab가 백신-관련 호흡기 질환 증가에 기여할 수 있다는 점에서, 백신의 안전성에 잠재적으로 중요한 지표이다. 본 발명의 데이터는 또한 RBD-12GS-I53-50이 RBD에서 동정된, 중화 Ab에 의해 인지되는 비-중첩성 에피토프들 수종을 표적화하는 Ab 반응을 유발한다는 것을, 보여준다. 여러가지 개별 에피토프들을 표적화하는 이러한 다클론성 반응은 관찰되는 중화 정도를 설명할 수 있으며, 탈출 돌연변이의 선택 및 출현 위험을 최소화할 것이다. 마지막으로, RBD-I53-50A 구성성분의 높은 생산 수율과 항원-보유한 RBD 나노입자의 견고한 안정성은 대량 제조를 가능하게 해준다.
방법
표 6. 재료
시약 또는 재료 근원 식별자
항체
CR3022 (ter Meulen et al., 2006) N/A
S309 (Pinto et al., 2020) N/A
B38 (Wu et al., 2020) N/A
염소 항-인간 HRP Invitrogen Cat #A18817 Lot #65-180-071919
염소 항-마우스 HRP Invitrogen Cat #626520 Lot #TG275230
말 항-마우스 HRP Cell Signaling Technology Cat #7076S
항-마우스 Fc Block BD Biosciences Cat#553142 RRID:AB_394657
항-마우스 B220 BUV737 BD Biosciences Cat#612838 RRID:AB_2738813
항-마우스 CD3 PerCP-Cy5.5 BD Biosciences Cat#551163 RRID:AB_394082
항-마우스 CD138 BV650 BD Biosciences Cat#564068 RRID:AB_2738574
항-마우스 CD38 Alexa™ Fluor 700 Thermo Fisher Scientific Cat#56-0381-82 RRID:AB_657740
항-마우스 GL7 ef450 Thermo Fisher Scientific Cat#48-5902-82 RRID:AB_10870775
항-마우스 IgM BV786 BD Biosciences Cat#743328 RRID:AB_2741429
항-마우스 IgD BUV395 BD Biosciences Cat#565988 RRID:AB_2737433
항-마우스 CD73 PE-Cy7 Thermo Fisher Scientific Cat#25-0731-82 RRID:AB_10853348
항-마우스 CD80 BV605 BD Biosciences Cat#563052 RRID:AB_273795
생물학적 샘플
BALB/c 마우스 Jackson Laboratory Cat #000651
Kymice™ Kymab
20/130 COVID-19 혈장 NIBSC 20/130
화학제, 펩타이드 및 재조합 단백질
AddaVax™ 보강제 InvivoGen Cat# vac-adx-10
ABTS ThermoFisher Cat# 37615
TMB SeraCare Cat# 5120-0083
트롬빈 Sigma Cat# T9326-150UN
고정된 파파인 ThermoScientific Cat# 20341
LysC-엔도프로테이나제 NEB Cat# P8109S
hACE2-Fc This study N/A
EZ-Link™ Sulfo-NHS-LC 바이오틴화 키트 Thermo Fisher Scientific Cat#21435
스트렙타비딘-APC Agilent Cat#PJ27S-1
스트렙타비딘-PE Agilent Cat#PJRS25-1
Anti-PE 마이크로비드 Miltenyi Biotec Cat#130-048-801
Anti-APC 마이크로비드 Miltenyi Biotec Cat#130-090-855
DyLight™ 755 항체 표지 키트 Thermo Fisher Scientific Cat#84538
AlexaFluor™ 647 단백질 표지 키트 Thermo Fisher Scientific Cat#A20173
실험 모델: 세포주
Expi 293F ThermoFisher Cat #A14527
Vero(C1008)E6 부착성 ECACC General Collection Cat #85020206
HEK-ACE2 부착성 BEI (Bloom lab으로부터 선물받음) NR-52511
HEK293T/17 부착성 ATCC Cat# CRL-11268
Vero E6 ATCC Cat# CRL-1586
재조합 DNA
pCMV-RBD-12GS-50A GenScript (본 연구) N/A
pCMVR-RBD-16GS-50A GenScript (본 연구) N/A
pCMV-RBD-8GS-50A GenScript (본 연구) N/A
S-2P 삼량체 GenScript (Walls et al. 2020) BEI NR-52421
RBD GenScript (Walls et al. 2020) BEI NR-52422
SARS-CoV-2 S 전장 GenScript (Walls et al. 2020) BEI NR-52420
뮤라인 백혈병 바이러스 gag-pol Millet and Whittaker 2016 N/A
pTG-루시퍼라제 Millet and Whittaker 2016 N/A
소프트웨어 및 알고리즘
UCSF ChimeraX (Goddard et al., 2018) https://www.rbvi.ucsf.edu/chimerax/
Prism™ Graphpad https://www.graphpad.com/scientific-software/prism/
FlowJo™ v10 FlowJo https://www.flowjo.com
기타
Octet™ Biosensors: 단백질 A Sartorius (ForteBio) Cat# 18-5010
Octet™ Biosensors: Anti-Penta-HIS (HIS1K) Sartorius (ForteBio) Cat# 18-5120
Octet™ Biosensors: NTA Sartorius (ForteBio) Cat# 18-5101
EM supplies 300메쉬 그리드 Ted Pella Cat# 01843-F
필터 페이퍼 Cytiva Cat# 1004047
우라닐 포르메이트 SPI Chem Cat# 02545-AA
Unis™ 캐필러리 카세트 Unchained Labs Cat# 201-1010
PrismA™ 단백질 A 수진 Cytiva Cat# 17549802
Superdex™ 200 인크리즈 SEC 컬럼 Cytiva Cat# 28-9909-44
Superose™ 6 인크리즈 SEC 컬럼 Cytiva Cat# 29091596
Talon™ 수지 TaKaRa Cat# 635652
VL26 Vantage L 컬럼 Millipore Cat# 96100250
Excel 수지 Cytiva Cat# 17371203
패터슨 수의과, 이소플루란, USP Patterson Cat# 07-893-1389
Eppendorf(R) 안전-락 미세원심분리관 1.5-mL Sigma Millipore Cat# T9661
BD Luerr-Lok™ 1-mL 시린지 BD Cat# BD309628
BD 1회용 바늘 25G x 7/8 VWR Cat# BD305124
BD PrecisionGlide™ 바늘 23Gx1 1/4 BD Ref# 305120
BD 1회용 바늘 27G x 1 1/4 VWR Cat# BD305136
EndoSafe™ LAL 검사 카트리지 Charles River Labs Cat # PTS20005F
Lemo21TM (DE3) New England BioLabs Cat#C2528J
이소프로필-B-D-티오갈락토시드 (IPTG) Sigma Aldrich Cat#I6758
카나마이신 설페이트 Sigma-Aldrich Cat#K1876
HiLoad™ S200 pg Cytiva Cat#28989336
Ni Sepharose™ 6 FF Cytiva Cat#17531808
HisTrap™ FF Cytiva Cat#17525501
세포주
HEK293F는 형질전환되고 현탁 배양에 적응된 인간 여성 배아 신장 세포 (Life Technologies)이다. HEK293F 세포는 293FreeStyle™ 발현 배지 (Life Technologies)에서 증식시키고, 37℃ 및 8% CO2에서 130 rpm 교반 하에 배양하였다. Expi293F™ 세포는 HEK293F 세포주 (Life Technologies)로부터 유래한다. Expi293F™ 세포는 Expi293™ 발현 배지 (Life Technologies)에서 36.5℃ 및 8% CO2, 150 rpm 교반 하에 배양하여 증식시켰다. VeroE6는 아프리카 녹색 원숭이로부터 유래한 암컷 신장 상피 세포이다. HEK293T/17은 여성 배아 신장 세포주 (ATCC)이다. HEK-ACE2 부착성 세포주는 BEI Resources, NIAID, NIH: 인간 안지오텐신-변환 효소 2를 발현하는 인간 배아 신장 세포 (HEK-293T), HEK-293T-hACE2 세포주, NR-52511로부터 수득하였다. 부착성 세포들 모두 DMEM + 10% FBS (Hyclone) + 1% 페니실린-스트렙토마이신이 담긴 플라스크에서 37℃ 및 8% CO2에서 배양하였다. Expi293F를 제외한 다른 세포주는 마이코플라스마 오염에 대해 검사 및 인증된 바 없다.
마우스
4주령의 암컷 BALB/c 마우스는 메인주 바 하버에 위치한 Jackson Laboratory에서 입수하였다. 동물 절차는 워싱턴 시애틀에 위치한 워싱턴 대학 및 NC 채플 힐에 위치한 노스캐롤라이나 대학의 동물 관리 및 사용 위원회의 승인 하에 수행하였다. Darwin™으로 알려진 Kymab's proprietary IntelliSelect™ 형질전환 마우스 플랫폼은 재정렬되지 않은 인간 항체 가변성 및 불변성 생식계열 레퍼토리를 가진 완전한 인간 항체 유전자 좌를 가지고 있다. 그래서, 이 마우스에 의해 생산되는 항체는 완전한 인간 항체이다.
피그테일 마카크
성체 수컷 피그테인 마카크 (Macaca nemestrina) 2마리를 본 실험에서 면역화하였다. 동물은 모두 미국 국제 실험실 동물 보호 승인 협회 (AAALAC)-인증 기관인 워싱턴 국립 영장류 연구 센터 (WaNPRC)에서 기존에 언급된 바와 같이 사육하였다 (Erasmus et al., 2020). 동물에 대해 수행된 모든 절차들은 워싱턴 대학의 동물 관리 및 사용 위원회 (IACUC)로부터 승인을 받았다.
회복기 인간 혈청
PCR 검사에서 SARS-CoV-2 양성인 개체 31명에서 감염 후 1-60일에 수집한 샘플에서 anti-SARS-CoV-2 S 항체 반응에 대한 프로파일을 수득하였으며, anti-S Ab 반응을 보인 29명을 코호트로 두었다 (도 4 및 5). 개체는 시애틀 워싱턴 대학에서 HAARVI 연구의 일환으로 등록하였다. 이들 개체에 대한 기본적인 사회인구학적 및 임상 데이터는 표 5에 요약 기술한다. 이 연구는 워싱턴 대학 인간 개체 분과 생명윤리위원회로부터 승인받았다 (STUDY00000959 및 STUDY00003376). 모든 실험은 2 이상의 기술적 레플리케이트 및 2 이상의 생물학적 레플리케이트로 수행하였다 (ELISA 및 슈도바이러스 중화 분석에 대해). 샘플 하나는 NIBSC의 20/130 COVID-19 혈장이다.
플라스미드 구축
SARS-CoV-2 RBD (BEI NR-52422) 구조체는 GenScript에서 N-말단 mu-포스파타제 신호 펩타이드와 C-말단 옥타-히스티딘 태그 (GHHHHHHHH)(서열번호 164)를 가진 pcDNA3.1-에 삽입하여 합성하였다. 구조체의 경계는 N-328RFPN331 및 528KKST531-C이다 (Walls et al., 2020). SARS-CoV-2 S-2P 엑토도메인 삼량체 (GenBank: YP_009724390.1, BEI NR-52420)는 GenScript에서 N-말단 mu-포스파타제 신호 펩타이드와 C-말단 TEV 절단부 (GSGRENLYFQG)(서열번호 165), T4 피브리틴 폴돈 (fibritin foldon)(GGGSGYIPEAPRDGQAYVRKDGEWVLLSTFL)(서열번호 166), 및 옥타-히스티딘 태그 (GHHHHHHHH)(서열번호 164)(Walls et al., 2020)를 가진 pCMV에 삽입하여 합성하였다. 구조체는 2P 돌연변이 (986 및 987 잔기에 프롤린 치환; (Pallesen et al., 2017)) 및 푸린 (furin) 절단부에서의 682SGAG685 치환을 가지고 있다. SARS-CoV-2 RBD는 삼량체 I53-50A 나노입자 구성성분의 N-말단에 글리신 및 세린 잔기 8, 12 및 16개로 구성된 링커를 이용해 유전자 융합하였다. RBD-8GS-I53-50A 및 RBD-12GS-I53-50A 융합체는 Genscript 사에서 pCMV에 삽입하여 합성 및 클로닝하였다. RBD-16GS-I53-50A 융합체는 Xba1 및 AvrII 제한효소 부위와 깁슨 어셈블리 (Gibson et al., 2009)를 이용해 pCMV/R에 클로닝하였다. RBD를 함유한 구성성분들 모두 N-말단 mu-포스파타제 신호 펩타이드와 C-말단 옥타-히스티딘 태그를 함유하였다. 마카크 또는 인간 ACE2 엑토도메인은 C-말단에 인간 Fc 단편 및 트롬빈 절단부를 암호화 서열에 유전자 융합하였다. hACE2-Fc는 GenScript 사에서 BM40 신호 펩타이드를 부가하여 합성 및 클로닝하였다. 플라스미드는 추후 박테리아 배양물에서 (NucleoBond Xtra Midi™ 키트) DNA 추출해 Expi293F 세포에 일시적으로 형질감염시키기 위한 플라스미드를 수득하기 위해, E. coli의 NEB 5-α 균주 (New England Biolabs)에 형질전환하였다. 본 실험에 사용한 모든 새로운 단백질들의 서열은 표 3에서 확인할 수 있다.
일시적인 형질감염
SARS-CoV-2 S 및 ACE2-Fc 단백질은 Expi293F 발현 배지 (Life Technologies)에서 33℃, 70% 습도 및 8% CO2에서 150 rpm 하에 교반하면서 현탁 배양한 Expi293F 세포에서 생산하였다. mL 당 세포 3백만개 밀도로 배양한 세포를 이용해 PEI-MAX™ (Polyscience)에 의해 배양물을 형질감염시켰다. 상층액을 원심분리 (4000 rcf에서 5분)하여 청징 처리하고, PDADMAC 용액을 최종 농도 0.0375% (Sigma Aldrich, #409014)로 첨가하여 2차 원심분리하였다 (4000 rcf에서 5분).
CR3022 중쇄 및 경쇄를 암호화하는 유전자를 GenScript에서 주문하여, pCMV/R에 클로닝하였다. 항체는 Expi293F 세포에서 중쇄 플라스미드 및 경쇄 플라스미드의 일시적인 공동-형질감염에 의해 PEI MAX™ (Polyscience) 형질감염 시약을 이용해 발현시켰다. 3 또는 6일 후 전술한 바와 같이 세포 상층액을 회수하고, 청징 처리하였다.
단백질 정제
His 태그를 가진 단백질은, 각각의 청징 처리된 상층액에 Tris-HCl pH 8.0을 최종 농도 45 mM로, 5 M NaCl을 최종 농도 ~310 mM으로 첨가하는 배치 결합 방법으로, 청징 처리된 상층액으로부터 정제하였다. 처리된 상층액에 탈론 코발트 친화성 수지 (Takara)를 첨가하고, 부드럽게 흔들면서 15분간 인큐베이션하였다. 0.2 ㎛ 필터를 이용한 진공 여과에 의해 수지를 수집하고, 이를 중력관 (gravity column)으로 옮겼다. 수지를 20 mM Tris pH 8.0, 300 mM NaCl으로 헹구고, 단백질을 3배 컬럼 부피의 20 mM Tris pH 8.0, 300 mM NaCl, 300 mM 이미다졸로 용출시켰다. 배치 결합 공정을 다시 반복하였으며, 1차 용출물과 2차 용출물을 합하였다. SDS-PAGE를 이용해 순도를 분석하였다. RBD-I53-50A 융합 단백질 IMAC 용출물을 >1 mg/mL까지 농축한 다음 수화한 10K 분자량 컷오프의 투석 카세트 (Thermo Scientific)에 넣어 50 mM Tris pH 7, 185 mM NaCl, 100 mM 아르기닌, 4.5% 글리세롤 및 0.75% w/v 3-[(3-콜라미도프로필)다이메틸암모니오]-1-프로판설포네이트 (CHAPS)에서 3회 투석하였다. S-2P IMAC 용출 분획은 ~1 mg/mL까지 농축한 다음 수화한 10K 분자량 컷오프의 투석 카세트 (Thermo Scientific)에 넣어 50 mM Tris pH 8, 150 mM NaCl, 0.25% L-히스티딘에서 3회 투석하였다. 고유한 불안정성으로 인해, S-2P 삼량체는 즉시 급속 냉동시켜 -80℃에서 보관하였다.
단일클론 항체 및 인간 및 마카크 ACE2-Fc를 발현하는 세포의 청징 처리된 상층액을 AKTA Avant150 FPLC (Cytiva)에서 MabSelect PrismA™ 2.6 x 5 cm 컬럼 (Cytiva)을 사용해 정제하였다. 결합된 항체는 5배 컬럼 부피의 20 mM NaPO4, 150 mM NaCl pH 7.2로, 5배 컬럼 부피의 20 mM NaPO4, 1 M NaCl pH 7.4로 순차적으로 헹군 다음, 3배 컬럼 부피의 100 mM 글리신 pH 3.0로 용출시켰다. 용출물에 2 M 트리즈마 염기를 최종 농도 50 mM로 첨가하여 중화하였다. SDS-PAGE에 의해 순도를 분석하였다.
전술한 바와 같이 (일시적인 형질감염 참조)(Stettler et al., 2016), 중쇄 및 경쇄를 발현하는 플라스미드가 일시적으로 공동-형질감염된 expiCHO 세포에서 Fab로서 재조합 S309를 발현시켰다. 단백질을 HiTrap™ 단백질 A Mab select Xtra™ 컬럼 (Cytiva)을 이용해 친화성-정제한 다음, HiTrap™ Fast 탈염 컬럼 (Cytiva)을 사용해 20 mM NaPO4, 150 mM NaCl pH 7.2에 대해 탈염 처리하였다. 단백질을 0.22 ㎛ 필터를 통과시켜 멸균 처리한 다음 사용시까지 4℃에서 보관하였다.
미생물 단백질 발현 및 정제
I53-50A 및 I53-50B.4.PT1 단백질은, 2 L 배플드 교반 플라스크 또는 10 L BioFlo 320 발효기 (Eppendorf)에서 배양한 LB (10 g 트립톤, 5 g 효모 추출물, 10 g NaCl) 중의 Lemo21(DE3)(NEB)에서 발현시켰다. 세포는 37℃에서 OD600 ~0.8까지 배양한 다음 1 mM IPTG를 첨가하여 유도하였다. 발현 온도를 18℃까지 낮추고, 세포를 ~16시간 동안 교반하였다. 세포를 회수하고, 50 mM Tris, 500 mM NaCl, 30 mM 이미다졸, 1 mM PMSF, 0.75% CHAPS 중에 18,000 psi 하에 Microfluidics M110P를 이용한 미세유동화에 의해 세포용해하였다. 세포용해물은, 2.6x10 cm Ni Sepharose™ 6 FF 컬럼 (Cytiva)에 주입하여 AKTA Avant150 FPLC 시스템 (Cytiva)에서 IMAC에 의해 정제하기 위해, 24,000 g에서 30분간 원심분리하여 청징 처리하였다. 대상 단백질은 백그라운드 50 mM Tris pH 8, 500 mM NaCl, 0.75% CHAPS 완충제 중의 이미다졸 30 mM -> 500 mM의 선형적인 농도 구배에 의해 용출시켰다. 피크 분획을 모아 10K MWCO 원심분리 필터 (Millipore)에서 농축하고, 멸균 여과 (0.22 μm)한 다음 Superdex™ 200 Increase 10/300 또는 HiLoad™ S200 pg GL SEC 컬럼 (Cytiva)에 50 mM Tris pH 8, 500 mM NaCl, 0.75% CHAPS 완충제를 이용해 주입하였다. I53-50A는 ~0.6 컬럼 부피 (CV)에서 용출된다. I53-50B.4PT1은 ~0.45 CV에서 용출된다. 사이징 후, 박테리아-유래 성분들을 검사하여, 나노입자 어셈블리에 사용하기 전 내독소 수준이 낮은지를 검증하였다.
시험관내 나노입자 어셈블리
정제한 개개 나노입자의 전체 단백질 농도를 UV/vis 분광광도계 (Agilent Cary 8454)에서 280 nm에서 흡광도를 측정하여 결정하고, 흡광 계수를 계산하였다 (Gasteiger et al., 2005). 다음 순서로 첨가하여 실온에서 조립 단계를 수행하였다: RBD-I53-50A 삼량체 융합 단백질 -> 원하는 최종 농도를 달성하기 위해 필요에 따라 완충제 -> 마지막으로, (50 mM Tris pH 8, 500 mM NaCl, 0.75% w/v CHAPS 중의) I53-50B.4PT1 오량체 구성성분, RBD-I53-50A:I53-B.4PT1의 몰 비율 1.1:1. 부분 결합가 RBD-I53-50 나노입자 (50% RBD-I53-50)를 제조하기 위해, RBD-I53-50A 및 비-변형된 I53-50A 삼량체 (50 mM Tris pH 8, 500 mM NaCl, 0.75% w/v CHAPS 중의)를 약간의 몰 과량 (1.1x)으로 I53-50B.4PT1에 첨가하였다. 모든 시험관내 RBD-I53-50 어셈블리는 적어도 30분간 부드럽게 교반하면서 2-8℃에서 인큐베이션한 다음 남아있는 조립되지 않은 성분을 제거하기 위해 SEC에 의해 정제하였다. 목적에 따라 여러가지 컬럼들을 사용하였다: Superose™ 6 Increase 10/300 GL 컬럼은 나노입자 크기를 추정하기 위한 분석 용도로 사용하고, Superdex™ 200 Increase 10/300 GL 컬럼은 소규모 파일럿 어셈블리에 대한 것으로 사용하고, HiLoad™ 26/600 Superdex™ 200 pg 컬럼은 나노입자 제조 용도로 사용하였다. 조립된 입자들은 Superose™ 6 컬럼에서 ~11 mL에서, Superdex™ 200 컬럼의 보이드 부피에서 용출된다. 조립된 나노입자를 멸균 여과 (0.22 ㎛)한 즉시 컬럼에 적용하고, 분획들을 모았다.
hACE2-Fc 및 CR3022 분해
hACE2-Fc를 트롬빈 프로테아제 (Sigma Aldrich)로 2.5 mM CaCl2의 존재 하에 트롬빈:단백질 1:300 w/w 비율로 사용해 분해하였다. 반응물을 주위 온도에서 16-18시간 동안 부드럽게 교반하면서 인큐베이션하였다. 인큐베이션한 후, 반응 혼합물을 Ultracel™ 10K 원심분리 필터 (Millipore Amicon Ultra)로 농축하고, 멸균 여과하였다 (0.22 ㎛). 절단된 hACE2 모노머를 비-전달된 hACE2-Fc 및 절단된 Fc 영역으로부터 단백질 A 정제 (상기 단백질 정제 참조)를 이용해 HiScreen MabSelect SuRe™ 컬럼 (Cytiva)에서 KTA avant 25 FPLC (Cytiva)를 사용해 분리하였다. 절단된 hACE2 단량체를 통과 분획에서 수집해 멸균 여과 (0.22 ㎛)한 다음 UV/vis에 의해 정량하였다.
LysC (New England BioLabs)를 10 mM Tris pH 8 중에 10 ng/㎕로 희석하고, LysC:IgG 1:2000 w/w 비율로 CR3022 IgG에 첨가한 다음 37℃에서 230 rpm으로 교반하면서 18시간 동안 진탕 배양하였다. 절단 반응물을 Ultracel™ 10K 원심분리 필터 (Millipore Amicon Ultra)로 농축한 다음 멸균 여과 (0.22 ㎛)하였다. 절단된 CR3022 mAb를 비-절단된 CR3022 IgG 및 절단된 IgG의 Fc 부분으로부터 전술한 바와 같이 단백질 A 정제를 이용해 분리하였다. 절단된 CR3022를 통과 분획에서 수집하고, 멸균 여과 (0.22 ㎛)한 다음 UV/vis에 의해 정량하였다.
생물층 간섭측정 (항원성)
항원성 분석을 Octet™ Red 96 시스템 (Pall Forte Bio/Sartorius)에서 BLI를 이용해 주위 온도에서 1000 rpm으로 교반하면서 수행 및 분석하였다. RBD-I53-50A 삼량체 구성성분 및 단량체 RBD를 카이네틱스 완충제 (1x HEPES-EP+ (Pall Forte Bio), 0.05% 탈지 밀크 및 0.02% 소듐 아지드)에 40 ㎍/mL로 희석하였다. 단량체 hACE2 및 CR3022 Fab를 카이네틱스 완충제에 750 nM로 희석하고, 최종 농도 3.1 nM로 3배 연속 희석하였다. 시약을 블랙 96웰 Greiner Bio-one 마이크로플레이트에 웰당 200 ㎕씩 후술한 바와 같이 적용하였다. RBD-I53-50A 구성성분 또는 단량체 RBD를 Anti-Penta-HIS (HIS1K) 바이오센서 상에 제조사의 지침 (Forte Bio)에 따라 고정하였으며, 단 다음과 같은 센서 인큐베이션 시간을 적용하였다. HIS1K 바이오센서를 수중에 10분간 수화한 다음, 카이네틱스 완충제에서 60초간 평형화하였다. HIS1K 팁에 희석한 삼량체 RBD-I53-50A 구성성분 또는 단량체 RBD를 150초간 로딩한 다음 카이네틱스 완충제로 300초간 헹구었다. 면역원이 고정된 HIS1K 바이오센서를 희석한 hACE2 모노머 또는 CR3022 Fab에 600초간 침지하여 결합 단계를 수행한 다음, 다시 바이오센서를 카이네틱스 완충제에 600초간 넣어 해리를 측정하였다. 데이터에서 베이스라인을 제하고, Pall™ ForteBio/Sartorius 분석 소프트웨어 (버전 12.0)를 사용해 플롯 피팅하였다. 도 8의 도표는 결합 단계 및 해리 단계를 도시한다.
생물층 간섭측정 (접근성)
주위 온도에서 1000 rpm으로 교반하면서 Octet™ Red 96 시스템 (Pall™ ForteBio/Sartorius)을 이용한 실시간 안정성 실험 및 접근성 실험으로, 단량체 RBD, RBD-I53-50A 삼량체 및 RBD-I53-50 나노입자에 대한 mACE2-Fc, CR3022 IgG 및 S309 IgG의 결합을 분석하였다. 단백질 샘플을 카이네틱스 완충제에 100 nM로 희석하였다. 그런 후, 완충제, 면역원 및 분석물을 블랙 96웰 Greiner Bio-one 마이크로플레이트에 웰 당 200 ㎕씩 넣었다. 단백질 A 바이오센서 (ForteBio/Sartorius)를 먼저 카이네틱스 완충제에 넣어 10분간 수화한 다음, 고정화 단계로서 카이네틱스 완충제에 10 ㎍/mL로 희석한 mACE2-Fc, CR3022 또는 S309 IgG에 침지하였다. 500초 후, 팁을 카이네틱스 완충제로 옮겨 60초간 베이스라인에 도달하게 두었다. 로딩된 바이오센서를 면역원에 30초간 침지하여 결합 단계를 수행하였으며, 바이오센서를 다시 카이네틱스 완충제에 다시 300초간 침지하여 해리 단계를 수행하였다. 데이터에서 베이스라인을 제한 후 ForteBio 분석 소프트웨어 (버전 12.0)를 사용해 도표로 작성하였다. 도 2의 도표는 600초간의 결합 및 해리를 나타낸다.
음성 염색 전자 현미경 검경
RBD-I53-50 나노입자를 먼저 50 mM Tris pH 7, 185 mM NaCl, 100 mM 아르기닌, 4.5% v/v 글리세롤, 0.75% w/v CHAPS에 75 ㎍/mL로 희석하고, S-2P 단백질은 50 mM Tris pH 8, 150 mM NaCl, 0.25% L-히스티딘 중의 0.03 mg/mL로 희석한 후, 샘플 3 ㎕를 새로운 글로우-방전되는 300 메쉬 구리 그리드에 도포하였다. 샘플을 그리드 상에서 1분간 인큐베이션한 다음 그리드를 물 방울 50 ㎕에 침지하고, 과량의 액체는 필터 페이퍼 (Whatman)로 닦아 제거하였다. 그런 후, 그리드를 0.75% w/v 우라닐 포르메이트 염료 6 ㎕에 침지하였다. 염료를 필터 페이퍼로 닦아 제거한 다음 그리드를 다시 염료 6 ㎕에 침지하여 ~70초간 인큐베이션하였다. 마지막으로, 염료를 닦아 제거하고, 1분간 건조시켰다. 준비한 그리드를 탈로스 모델 L120C 전자 현미경에서 45,000x (나노입자) 또는 92,000x 배율 (S-2P)로 촬영하였다.
동적 광 산란
동적 광 산란 (DLS)을 이용해, UNcle Nano-DSF (UNchained Laboratories)에서 RBD-I53-50 나노입자 샘플의 유체역학 직경 (Dh)과 다분산성 % (%Pd)를 측정하였다. 샘플을 8.8 ㎕ 석영 모세관 카세트 (UNi, UNchained Laboratories)에 도포하고, 레이저의 자동-감쇠를 적용해 5초씩 10회 획득으로 측정하였다. RBD 나노입자 완충제 중의 4.5% v/v 글리세롤로 인해 증가된 점도는 Dh 측정에서 UNcle™ 클라이언트 소프트웨어에 의해 감안하였다.
구아니딘 HCl 변성
단량체 RBD, RBD-I53-50A 융합 단백질 및 RBD-I53-50 나노입자 면역원을, 50 mM Tris pH 7.0, 185 mM NaCl, 100 mM 아르기닌, 4.5% v/v 글리세롤, 0.75% w/v CHAPS 및 0 M 내지 6.5 M 범위에서 0.25 M 간격으로 구아니딘 클로라이드 [GdnHCl]에 2.5 μM까지 희석하였으며, 3세트로 준비하였다. S-2P 삼량체 역시 50 mM Tris pH 8, 150 mM NaCl, 0.25% L-히스티딘 및 동일한 GuHCl 농도 범위에서 2.5 μM으로 희석하였다. 희석물들은 파이펫팅으로 10x 혼합하였다. 그런 후, 샘플을 주위 온도에서 18-19시간 동안 인큐베이션하였다. Nano-DSF (UNcle™, UNchained Laboratories) 및 8.8 ㎕ 석영 모세관 카세트 (UNi™, UNchained Laboratories)를 이용해 266 nm에서 여기시키고, 200 nm - 750 nm에서 방출을 측정하여 25℃에서 형광 스펙트럼을 3세트로 수집하였다.
내독소 측정
EndoSafe™ Nexgen-MCS 시스템 (Charles River)을 이용해 단백질 샘플 내 내독소 수준을 측정하였다. 샘플을 내독소-비함유 LAL 시약 물에 1:50 또는 1:100으로 희석하고, 이를 EndoSafe™ LAL 시약 카트리지의 웰에 넣었다. Charles River EndoScan™-V 소프트웨어를 사용해 내독소 함량을 분석하였으며, 자동적으로 희석 인수에 대해 역-계산하였다. 내독소 값을 EU/mL로 기록한 다음 UV/vis 측정값에 기반하여 EU/mg으로 변환하였다. 면역화에 적합한 샘플의 역치는 <50 EU/mg이다.
UV/vis
Agilent Technologies Cary™ 8454에서 자외선-가시광선 분광도 (UV/vis)를 측정하였다. 샘플을 10 mm, 50 ㎕ 석영 셀 (Starna Cells, Inc.)에 적용하고, 180 - 1000 nm에서 흡광도를 측정하였다. 측정하고 단일 기준 파장 베이스라인을 제하여 수득한 280 nm에서의 순 흡광도를, 계산된 흡광 계수 및 분자량과 함께 사용해, 단백질 농도를 구하였다. 320/280 nm에서의 흡광도 비율을 이용해, 실시간 안정성 실험 샘플에서 상대적인 응집 수준을 결정하였다. 샘플을 각각의 정제/기기 블랭킹 완충제를 사용해 흡광도 0.1 내지 1.0으로 희석하였다. UV/vis 장치에서 수득한 모든 데이터는 845x 자외선/가시광선 시스템 소프트웨어에서 가공 처리하였다.
글리칸 프로파일 획득
당사슬 (glycoform) 분포 및 점유 결정 (occupancy determination)을 비롯한 부위-특이적인 당화 프로파일을 동정하기 위해, 바텀-업 질량 분광 측정 (MS) 방식을 이용하였다. 1 mg/mL 단량체, 8GS, 12GS 및 16GS RBD 단백질 분액들을 준비하여, RBD 변이체 4종에서 N331 및 N343의 당화 프로파일을 조사하였다. 안정화된 스파이크 엑토도메인 (S-2P) 상의 포괄적인 당 프로파일링을 1.5 mg/mL SARS-CoV-2 S-2P 단백질과 병행하여 수행하였다. 모든 샘플은 25 mM Tris (pH 8.0), 7 M 구아니디늄 클로라이드 (GdnHCl) 및 50 mM 다이티오트레이톨 (DTT)이 함유된 용액에서 90℃에서 30분간 변성시켰다. 신선한 요오도아세트아미드 (IAA)를 100 mM까지 첨가하여 실온에서 암 조건 하에 1시간 인큐베이션하여, 환원된 시스테인을 알킬화하였다. 그런 후, 50 mM의 과량의 DTT를 첨가해 남아있는 IAA를 퀀칭하였다. 샘플을 10 mM Tris (pH 8.0), 2 mM 칼슘 클로라이드 용액으로 11배 희석해, GndHCl 농도를 0.6 M로 낮추었다. 그런 다음, 각 샘플을 절반씩 나누었다. 절반 (275 ㎕)은 재조합 펩타이드 N-글리카나제 F (GST-PNGase F)(Krenkova et al., 2013) 10 유닛과 혼합하고, 37℃에서 1시간 동안 인큐베이션하여 당화된 Asn을 탈당화된 Asp로 변환하였다.
프로테아제 분해를 다음과 같은 방식으로 수행하였다: 모든 RBD 샘플과 S-2P 샘플 하나를, RBD에 대해 1:40 (w/w) 비율로, 그리고 S-2P에 대해 1:30 (w/w) 비율로 Lys-C를 사용해 37℃에서 4시간 동안 분해한 다음, 동일한 비율 및 조건에서 밤새 Glu-C 분해하였다. 나머지 S-2P 샘플 3개는 트립신, 키모트립신 및 알파 세포용해 프로테아제 각각을 1:30 (w/w) 비율로 사용해 밤새 37℃에서 분해하였다. 사용한 모든 분해 프로테아제들은 MS 등급 (Promega)이었다. 다음날, 0.02% 포름산 (FA, Optima™, Fisher)으로 분해 반응물을 퀀칭하였다.
S-2P 샘플 4종은 Orbitrap Fusion™ 질량 분광기 (Thermo Fisher)에서 nano LC-MS에 의해 당사슬을 확인하였다. 분해 샘플을 Sep-Pak C18 카트리지 (Waters)에 의해 제조사의 권고 프로토콜에 따라 탈염 처리하였다. 2 cm 트랩핑 컬럼과 35 cm 분석 컬럼을 5 μM ReproSil-Pur™ C18 AQ 비드 (Dr. Maisch)가 충진된 용융 실리카 (100 ㎛ ID)에서 신선하게 준비하였다. 샘플 8 ㎕를 주입하고, 60분간 0.1% FA 중의 아세토니트릴 2% -> 30%의 선형적인 농도구배를 수행한 후 80% 아세토니트릴을 10분간 적용해, 운영하였다. EThcD 방법을 다음과 같이 최적화하였다: 이온 소스: 파지티브 모드의 경우 2.1 kV; 이온 이동관 온도: 350 ℃; 해상도: MS1 = 120000, MS2 = 30000; AGC 표적: MS1 = 2e5, MS2 = 1e5; 및 주입 시간: MS1 = 50 ms, MS2 = 60 ms.
Byonic™ 및 Byologic™ (Version 3.8, Protein Metrics Inc.)에서 6 ppm 전구체 및 10 ppm 프래그먼트 질량 허용 (fragment mass tolerance)을 적용하여 글리코펩타이드 데이터를 가시화하고 가공 처리하였다. 단백질 메트릭스 PMI-Suite에서 N-글리칸 309 포유류 데이터베이스를 이용해 글리코펩타이드를 검색하였으며, 보정한 c- 및 z-프래그먼트 이온 할당을 기반으로 점수를 매겼다. 참-양성 (true-positive) 물질은 204 (HexNAc 이온) 및 366 (HexNAcHex 이온)에서 글리칸 옥소늄 이온의 존재 및 탈당화된 샘플의 대응되는 스펙트럼에서의 부재에 의해 추가로 검증하였다. 각 당사슬의 상대적인 존재율 (relative abundance)을 Byologic™에서 분석한 피크 면적으로 결정하였다. 당사슬을 기존 연구에서 언급된 바와 같이 (Watanabe et al., 2020) 올리고 (올리고만노스), 하이브리드 및 복합체 뿐 아니라 복합체 내 서브타입으로 분류하였다. HexNAc(2)Hex(9-5)는 M(annose)9 - M5이고; HexNAc(3)Hex(5-6)은 하이브리드로 분류되고; HexNAc(3)Hex(3-4)X는 A1 서브타입이고; HexNAc(4)X는 A2/A1B이고; HexNAc(5)X는 A3/A2B이고, HexNAc(6)X는 A4/A3B 서브타입이다. 푸코실화된 하이브리드 및 복합체 형태는 각각 FHybrid 및 FComplex (예, FA1)로 나타낸다.
Acquity™ UPLC 시스템 (Waters)이 커플링된 Synapt G2-Si™ TOF 질량 분광기에서 LC-MS에 의해, RBD 변이체 4종에 대한 글리칸 점유율 분석 및 당사슬 결정을 수행하였다. 샘플은 Waters CSH C18 1 x 100 mm 1.7 ㎛ 컬럼에서 30분간 B 3% -> 40%의 선형적인 농도구배 (A: 98% 물, 2% 아세토니트릴, 0.1% FA; B: 100% 아세토니트릴, 0.1% FA)를 적용하여 분리시켰다. 전구체 질량 범위 300-2000, MS/MS 질량 범위 50-2000 및 70-100 V 경사형 붕괴 에너지를 적용하여, 데이터 의존적인 획득 (DDA) 방법을 이용하였다. 가장 크고 중첩되지 않는 동위원소 피크들에 대한 크로마토그래피 피크를 결정하고, MassLynx™ (Waters)에서 적분하였다. 달리 명시되지 않은 한, 이용한 모든 물 및 유기 용매는 MS 등급 (Optima™, Fisher)이었다. 비-당화된 (Asn) 글리코펩타이드 : 탈당화된 (Asp)의 피크 면적 비율을 이용해, 각 부위에서 글리칸 점유율을 측정하였다.
수소/중수소-교환 질량 분광 측정
3 ㎍의 단량체 RBD 및 RBD-8GS-I53-50A를 중수소화 완충제 (pH* 7.6, 85% D2O, Cambridge Isotope Laboratories, Inc.)에서 각각 3초, 60초, 1800초 및 72000초간 23℃에서 인큐베이션하고 H/D 교환 (HDX)하였다. 그런 후, 샘플을 빙랭한 퀀치 완충제 (200 mM 트리스(2-클로르에틸) 포스페이트 (TCEP), 8 M 우레아, 0.2% 포름산)와 최종 pH 2.5에서 1:1로 혼합한 다음 즉시 액체 질소에서 급속 냉동하였다. 샘플을 인-라인 펩신 분해 처리하고, Synapt G2-Si™ TOF 질량 분광기 (Waters)에서 기존에 언급된 바와 같이 (Verkerke et al., 2016) LC-MS-IMS로 분석하였으며, 18분 농도구배를 적용하였다. 중수소화되지 않은 샘플의 LC-MS 운영에서 펩신 분해 용출물을 수집하고, 이를 스피드벡에서 건조한 다음 중수소화 완충제에서 1시간 동안 85℃에서 인큐베이션하고, 다른 모든 HDX 샘플과 마찬가지로 퀀칭하여, 완전한 중수소화 대조군을 준비하였다. 전체 샘플들에서 일관된 표지 조건을 보장하기 위해 각 샘플에 내부 교환 표준물질 (Pro-Pro-Pro-Ile [PPPI] 및 Pro-Pro-Pro-Phe [PPPF])을 첨가하였다 (Zhang et al., 2012). 상기 당 프로파일링에서 언급된 설정으로, Orbitrap Fusion™ 질량 분광기 (Thermo Fisher)에서 nano LC-MS에 의해 중수소화되지 않은 샘플에 대한 펩신 분해를 분석하였다. 그런 후, Byonic™에서 데이터를 처리해, 펩타이드 참조 목록을 입수하였다. DriftScope™ (Waters)를 사용해 펩타이드를 수동 검증하였으며, 오르소고날 체류 시간 (orthogonal retention time)(rt) 및 이동 시간 (dt) 좌표와 함께 동정하였다. 중수소 흡수 분석은 HX-Express v2 (Guttman et al., 2013; Weis et al., 2006)를 이용해 수행하였다. 펩타이드 스펙트럼에서 이항 피팅을 적용해 피크를 동정하였다. 중수소 흡수 수준을 완전한 중수소화 표준물질을 기준으로 표준화하였다.
마우스 면역화 및 기회 감염
메인주 바 하버에 위치한 Jackson Laboratory에서 4주령의 BALB/c (Stock: 000651) 암컷 마우스를 구입하고, 미국 국제 실험실 동물 보호 승인 협회 (AAALAC)에서 인증한 워싱턴 주 시애틀에 위치한 워싱턴 대학의 비교 의학 시설에서 사육하였다. 6주령에, 투여군 당 마우스 10마리에 감작 면역화로 백신을 접종하고, 3주 후 2차 백신 접종으로 부스팅하였다. 접종하기 전, 면역원 현탁제를 AddaVax™ 보강제 (Invivogen, San Diego, CA)와 1:1 vol/vol로 부드럽게 혼합하여, 항원의 최종 농도가 0.009 또는 0.05 mg/mL이 되게 하였다. 마우스의 각 뒷다리 비복근에 27-게이지 바늘 (BD, San Diego, CA)을 사용해 면역원을 주사 부위 당 50 ㎕씩 (총 100 ㎕) 이소플루란 마취 하에 근육내 주사하였다. 혈청을 수득하기 위해, 감작 면역화 및 부스트 면역화 후 2주 경과시 모든 마우스에서 채혈하였다. 혈액은 턱밑 정맥 천공을 통해 채혈하고, 1.5 mL 플라스틱 에펜도르프 시험관에 넣어 실온에서 30분간 두어 응고되게 하였다. 이를 2000 g에서 10분간 원심분리하여 헤마토크릿으로부터 혈청을 분리하였다. 분리한 혈청을 56℃에서 60분간 인큐베이션하여 혈청 내 보체 인자 및 병원체를 열-불활화하였다. 혈청은 사용시까지 4℃ 또는 -80℃에서 보관하였다. 부스트 후 6주차에, 마우스를 워싱턴 주 시애틀 워싱턴 대학의 비교 의료 시설에서, 채플 힐 노르캐롤리나 대학의 AAALAC 인증된 동물 생물 안정성 레벨 3 (ABSL3) 실험실로 이동시켰다. 7일간 적응 기간을 거친 후, 케타민/크실라진 혼합물로 마우스를 마취하고, 백신 효능 (IACUC 프로토콜 20-114.0)을 평가하기 위해 마우스-적응된 SARS-CoV-2 MA 균주를 105 플라크-형성 단위 (pfu)로 비강내 기회 접종하였다. 감염 후, 실험을 종료하는 감염 후 2일차까지 매일 체중을 체크하였으며, 감염 후 2일차에 폐 및 비갑개 조직을 회수하여 플라크 분석을 통해 바이러스 부하를 평가하였다. 모든 실험은 워싱턴주 시애틀의 워싱턴 대학 및 NC 채플 힐 노스캐롤리나 대상에서 허가된 동물 관리 및 사용 위원회 프로토콜에 따라 수행하였다.
면역화 (Kymab Darwin™ 마우스)
Kymab Darwin™ 마우스 (수컷 및 암컷 혼합, 10주령)에, 투여군 당 마우스 5마리에, 감작 면역화로 백신을 접종한 다음 3주 후 2차 백신 접종으로 부스팅하였다. 접종하기 전, 면역원 현탁제를 AddaVax™ 보강제 (Invivogen)와 1:1 vol/vol로 부드럽게 혼합하여, 항원의 최종 농도가 0.009 또는 0.05 mg/mL이 되게 하였다. 마우스의 각 뒷다리 경골근에 30-게이지 바늘 (BD)을 사용해 면역원을 주사 부위 당 20 ㎕씩 (총 40 ㎕) 이소플루란 마취 하에 근육내 주사하였다. 마지막 부스트는 보강제 첨가 없이 7주차에 정맥내로 (50 ㎕)로 투여하였다. 5일 후 홈 오피스 스케줄 1 (CO2 농도 증가)에 따라 마우스를 희생시키고, 비장, 림프절 및 골수를 냉동 보존하였다. 각 투여 (0주, 2주, 5주, 및 8주 마지막 채혈) 후 2주차에 전혈 (0.1 ml)을 채혈하였다. 2000 g에서 10분간 원심분리하여 헤마토크릿으로부터 혈청을 분리하였다. 혈청은 -20℃에서 보관하고, ELISA에 의해 역가를 모니터링하였다. 영국 내무부 라이센스 70/8718 및 웰컴 트러스트 생거 연구소 동물 복지 및 윤리 검토 위원회의 승인 하에 마우스들을 모두 사육하였으며, 모든 절차를 이행하였다.
ELISA
anti-S-2P ELISA의 경우, 2 ㎍/mL S-2P 25 ㎕를 384웰 Nunc Maxisorp™ (ThermoFisher) 플레이트에 PBS 중에 첨가하고, 4℃에서 밤새 코팅하였다. 다음날, 플레이트를 플레이트 세척기 (BioTek)를 사용해 트리스 완충화된 염수 Tween (TBST)으로 4번 헹구고, TBST 중의 2% BSA로 1시간 동안 37℃에서 차단 처리하였다. 플레이트를 TBST에서 4번 헹구고, 1:25 또는 1:50에서 시작해 TBST 25 ㎕에서 마우스, NHP 또는 인간 혈청을 1:5로 연속 희석한 다음 37℃에서 1시간 동안 인큐베이션하였다. 플레이트를 TBST에서 4회 헹군 다음 항-마우스 (Invitrogen) 또는 항-인간 (Invitrogen) 호스래디시 퍼옥시다제-접합 항체를 1:5,000으로 희석하고, 25 ㎕를 각 웰에 첨가한 후 37℃에서 1시간 동안 인큐베이션하였다. 플레이트를 TBST에서 4번 헹구고, TMB (SeraCare) 25 ㎕를 모든 웰에 첨가하여 실온에서 5분간 두었다. 반응물에 1N HCl 25 ㎕를 첨가하여 퀀칭하였다. 즉시 플레이트를 VarioSkanLux™ 플레이트 리더 (ThermoFisher)에서 450 nm에서 측정하고, 데이터를 Prism™ (GraphPad)에서 비-선형 회귀 시그모이드, 4PL을 이용해 도표로 작성 및 피팅하였으며, X는 곡선 피팅으로부터 EC50 값을 결정하기 위한 로그(농도)이다.
슈도바이러스 생산
기존 (Millet and Whittaker, 2016; Walls et al., 2020)에 언급된 바와 같이 MLV-기반의 SARS-CoV-2 S, SARS-CoV S 및 WIV-1 슈도타입들을 생산하였다. 간략하게는, HEK293T 세포에 S-암호화 플라스미드, MLV Gag-Pol 패키징 구조체 및 루시퍼라제 리포터를 암호화하는 MLV 전달 벡터를 리포펙타민™ 2000 (Life Technologies)을 제조사의 지침에 따라 공동-형질감염시켰다. 세포를 Opti-MEM으로 3번 헹군 다음, 형질감염 배지와 함께 37℃에서 5시간 동안 배양하였다. 10% FBS가 첨가된 DMEM을 첨가하여 60시간 동안 두었다. 이를 2,500 g에서 회전시켜 상층액을 회수하고, 이를 0.45 ㎛ 필터를 통해 여과한 다음 100 kDa 막을 사용해 10분간 2,500 g에서 농축한 후 분액하여 -80℃에서 보관하였다.
슈도바이러스 유입 및 혈청 중화 분석
HEK-hACE2 세포는 37℃ 배양기 (ThermoFisher)에서 10% FBS (Hyclone) 및 1% PenStrep이 첨가된 DMEM 중에 8% CO2 하에 배양하였다. 감염 하루 전에, 폴리-라이신 (Sigma) 40 ㎕를 96웰 플레이트에 넣어 5분간 교반하면서 인큐베이션하였다. 플레이트에서 폴리-라이신을 제거하여 5분간 건조한 후 DMEM으로 1번 헹군 다음 세포를 접종하였다. 다음날, 세포가 80% 컨플루언스인지를 확인하였다. 96웰 플레이트의 절반에서, DMEM으로 혈청의 1:3 연속 희석을, 1:3 내지 1:66 처음 희석으로 시작해 최종 부피 22 ㎕로 수행하였다. 그런 후, 슈도바이러스 22 ㎕를 연속 희석물에 첨가하여 실온에서 30-60분간 인큐베이션하였다. HEK-hACE2 플레이트에서 배지를 제거하고, 세포에 혈청/바이러스 혼합물 40 ㎕를 첨가해 2시간 동안 37℃ 및 8% CO2 하에 인큐베이션하였다. 인큐베이션한 후, 세포에 20% FBS 40 ㎕ 및 DMEM 함유 2% PenStrep를 첨가하여 48시간 동안 두었다. 48시간 감염 후, 세포에 배양 부피의 절반 (40 ㎕ 첨가)으로 One-Glo-EX™(Promega)를 첨가하고, 5분간 암 조건에서 인큐베이션한 다음 Varioskan™ LUX 플레이트 리더 (ThermoFisher)에서 판독값을 측정하였다. 측정은 각 군별 마우스 혈청 샘플 총 10종에 대해 적어도 2세트로 수행하였다. Prism™(GraphPad)에서 세포 단독 0 및 1:2 바이러스 단독 100% 설정에 따라 상대적인 루시퍼라제 유닛을 표현 및 표준화하였다. 표준화된 반응 대비 log(저해제)의 비선형적인 회귀에 의해 그래프 곡선 피팅함으로써 IC50 값을 결정하였다. 만-휘트니 검정으로 2개의 군을 비교해, 통계적인 차이가 있는지를 확인하였다.
살아있는 바이러스 생산
기존 (Hou et al., 2020)에 언급된 코로나바이러스 리버스 제네틱스 시스템을 통해, ORF7이 나노루시퍼라제 유전자 (nanoLuc)로 치환된 SARS-CoV-2-nanoLuc 바이러스 (WA1 균주)와 마우스-적응된 SARS-CoV-2 (SARS-CoV-2 MA)(Dinnon et al., 2020)를 구축하였다. 10% Hyclone™ Fetal Clone II (GE #SH3006603HI), 1% 비-필수 아미노산 및 1% Pen/Strep이 첨가된 DMEM 글루코스 고 농도 배지 (Gibco #11995065)에서 배양한 Vero E6 세포 (ATCC-CRL1586)에서, 37℃ +5% CO2 배양기를 이용해, 재조합 바이러스를 구축하였다. 재조합 SARS-CoV-2를 구축하기 위해, 양쪽에 5' T7 프로모터 및 3' 폴리A 꼬리가 위치한 SARS-CoV-2의 전장 게놈을 일괄적으로 암호화하는 DNA 단편 7종을 라이게이션하고, 시험관내에서 전사하였다. 전사된 RNNA를 Vero E6 세포에 전기천공으로 투입하여, P0 바이러스 스톡을 제조하였다. 시드 바이러스를 Vero E6 세포에서 낮은 moi에서 48시간 동안 2번 증폭시켜, 워킹 스톡을 준비하였으며, 이를 플라크 분석으로 역가를 측정하였다 (Hou et al., 2020). 라이게이션 및 전기천공 단계를 비롯한 모든 살아있는 바이러스 실험들은 생물 안전성 레벨 3 (BSL-3) 조건에서 음압 하에 개인 동력-공기 정화 호흡기가 장착된 타이벡 슈트를 입은 조작자에 의해 수행하였다.
루시퍼라제-기반의 혈청 중화 분석, SARS-CoV-2-nanoLuc
분석하기 24시간 전에 96웰 플레이트에 Vero E6 세포를 2x104 세포/웰로 접종하였다. SARS-CoV-2-nanoLuc 바이러스 (Hou et al., 2020) 100 pfu를 혈청과 1:1 비율로 혼합하여, 37℃에서 1시간 동안 인큐베이션하였다. 각 샘플에 대해 농도 1:20 (표준) 또는 1:2000 (고 중화제)에서 시작해 8-포인트, 3배 희석 그래프를 작성하였다. 바이러스와 혈청 혼합물을 각각의 웰에 첨가하고, 37℃ + 5% CO2에서 48시간 동안 인큐베이션하였다. Nano-Glo™ 루시퍼라제 분석 시스템 (Promega, WI)에서 제조사의 프로토콜에 따라 SpectraMax™ M3 발광측정기 (Molecular Device)를 사용해 루시퍼라제 활성을 측정하였다. 저해 % 및 50% 저해 농도 (IC50)를 다음의 등식으로 계산하였다: [1-(샘플 처리 RLU/ 모의 처리 RLU)] x 100%. GraphPad Prism™ 8.3.0에서 시그모이드 용량-반응 (가변적인 기울기) 곡선에 데이터 포인트를 피팅하여, 50% 저해 역가 (IC50)를 계산하였다.
사량체 제조
재조합 SARS-CoV-2 S-2P 삼량체를 EZ-Link™ Sulfo-NHS-LC 바이오티닐화 키트 (ThermoFisher)를 사용해 바이오티닐화하고, 스트렙타비딘-APC (Agilent)를 이용해 기존 (Krishnamurty et al., 2016; Taylor et al., 2012)에 기술된 바와 같이 사량체화하였다. SARS-CoV-2 S의 RBD 도메인을 바이오티닐화하고, 스트렙타비딘-APC (Agilent)를 이용해 사량체화하였다. SA-APC를 Dylight™ 755에 DyLight 755 항체 표지 키트 (ThermoFisher)를 사용해 접합하고, 세척하여 결합되지 않은 DyLight 755를 제거한 다음 과량의 관련없는 His-태그가 달린 바이오틴화된 단백질과 인큐베이션하여, APC 디코이 시약을 제조하였다. SA-PE를 Alexa Fluor 647에 AF647 항체 표지 키트 (ThermoFisher)를 사용해 접합함으로써 동일한 방식으로 PE 디코이를 제조하였다.
마우스 면역화, 세포 농화 및 유세포 측정
B 세포 표현형을 확인하기 위해, 6주령의 BALB/c 암컷 마우스에, 투여군 당 3마리에, 0일에 AddaVax™ 보강제가 1:1 vol/vol로 혼합된 SARS-CoV-2 항원 (S-2P 삼량체 또는 RBD, 그러나 I53-50 나노입자로의 매스는 포함하지 않음) 5 ㎍을 함유한 백신 제형을 주사 부위 당 50 ㎕씩 근육내 주사하여 면역화하였다. 11일에 서혜부 및 슬와 림프절을 회수하기 위해 모든 실험 마우스들을 안락사시켰다. 실험은 2회 반복하였다. 개개 마우스에서 슬와 및 서혜부 림프절을 채취하여, 모았다. 림프절을 으깨고 100 ㎛ Nitex™ 메쉬를 통해 여과하여, 세포 현탁물을 준비하였다. 세포는 2% FBS 및 Fc 블록 (2.4G2)을 함유한 PBS에 재현탁하고, 10 nM 디코이 사량체와 함께 실온에서 20분간 인큐베이션하였다. RBD-PE 사량체 테트라머 및 Spike-APC 사량체를 10 nM 농도로 첨가하여, 얼음 위에서 20분간 인큐베이션하였다. 세포를 헹구고, 얼음 위에서 anti-PE 및 anti-APC 자기 비드와 30분간 인큐베이션한 다음 자성을 띠는 LS 컬럼 (Miltenyi Biotec)으로 통과시켰다. 얼음 위에서 20분 동안 항-마우스 B220 (BUV737), CD3 (PerCP-Cy5.5), CD138 (BV650), CD38 (Alexa Fluor™ 700), GL7 (eFluor™ 450), IgM (BV786), IgD (BUV395), CD73 (PE-Cy7) 및 CD80 (BV605)와 결합된 B 세포를 염색하였다. 세포는 Cytek Aurora™에서 조작하였으며, FlowJo™ 소프트웨어 (Treestar)에서 분석하였다. 세포 카운트는 Accucheck™ 세포 카운팅 비드를 이용해 결정하였다.
NHP 면역화
0일 및 28일에 피그테일 마카크에 RBD-12GS-I53-50 나노입자 (RBD 항원 88 ㎍) 250 ㎍을 주사하여 면역화하였다. 감작 후 0일, 10일, 14일, 28일, 42일 및 56일에 혈액을 채혈하였다. 기존 (Erasmus et al., 2020)에 언급된 바와 같이 혈청 및 혈장을 수집하였다. 백신 접종 또는 채혈하기 전에, 케타민 (Ketaset®; Henry Schein)을 근육내 주사 (10 mg/kg)하여 동물을 진정시켰다. 접종하기 전, 항원 최종 농도 0.250 mg/mL이 되도록, 면역원 현탁제를 AddaVax™ 보강제 (Invivogen, San Diego, CA)와 1:1 vol/vol로 부드럽게 혼합하였다. 0일 및 28일에 주사 부위 당 1 mL씩 대퇴사두근 양쪽에 백신을 근육내 전달하였다. 모든 주사 부위는 주사하기 전 면도하였으며, 모든 국소 반응 징후를 주사 후 모니터링하였다. 각 실험 시점에 동물에서 모든 신체 검사와 전체 건강 검사를 기존 (Erasmus et al., 2020)에 언급된 바와 같이 수행하였으며, 부작용은 관찰되지 않았다.
경쟁 생물층 간섭측정
NHP 혈청으로부터 Fab 정제는 (Boyoglu-Barnum et al., 2020)으로부터 조정하였다. 간략하게는, 56일 혈청 1 mL을 PBS 10 mL로 희석하고, 3x PBS로 세척한 단백질 A 비드 (GenScript) 1 mL과 밤새 37℃에서 교반하면서 인큐베이션하였다. 다음날, 비드를 중력 흐름 컬럼을 사용해 PBS로 잘 헹구고, 결합된 항체는 0.1 M 글리신 pH 3.5를 사용해 1M Tris-HCl (pH 8.0)로 최종 농도 100 mM로 용출시켰다. 통과한 혈청 및 초기 세척액을 밤새 비드에 다시 결합시키고, 다시 2차 용출을 반복 실시하였다. IgG를 농축하고 (Amicon 30 kDa), PBS로 완충제 교환하였다. 농축하고 모은 IgG에 2x 분해 완충제 (40 mM 소듐 포스페이트 pH 6.5, 20 mM EDTA, 40 mM 시스테인)를 첨가하였다. 1x 분해 완충제 (20 mM 소듐 포스페이트, 10 mM EDTA, 20 mM 시스테인, pH 6.5)로 금방 세척한 재현탁한 고정된 파파인 수지 (ThermoFisher Scientific) 500 ㎕를, 정제한 IgG에 2x 분해 완충제 중에 첨가하고, 샘플을 37℃에서 5시간 동안 교반하였다. 수지로부터 상층액을 분리하고, 수지 세척물을 수집해 수지 통과 분획과 합쳤다. 합친 상층액을 0.22 ㎛에서 멸균 여과하여, 중력 흐름 컬럼에서 PBS-세척한 단백질 A 비드에 6x로 적용하였다. 컬럼을 상기와 같이 용출시키고, 파파인 절차를 분해하지 않은 IgG를 사용해 밤새 반복하여 수율을 높였다. 단백질 A 통과 분획을 모아 농축하고 (Amicon 10 kDa), 완충제를 PBS로 교체하였다. SDS-PAGE에서 순도를 체크하였다.
Octet™ Red 96 시스템 (Pall™ Forte Bio/Sartorius)에서 BLI를 이용해 30℃에서 1000 rpm으로 교반하면서 에피토프 경쟁을 수행 및 분석하였다. NTA 바이오센서 (Pall™ Forte Bio/Sartorius)를 수중에 10분 이상 수화한 후, 10x 카이네틱스 완충제 (KB)(Pall™ Forte Bio/Sartorius)에서 60초간 평형화하였다. 10x KB에서 300초간 베이스라인을 획득하기 전 100초간 10x KB 중의 10 ng/㎕ 단량체 RBD를 로딩하였다. 그 후, 10x KB에 5000 nM로부터 1:3 연속 희석한 다클론 Fab 희석물에 팁을 2000초 침지하거나 또는 10x KB 중에 두었다. 다클론 Fab 농도에 따라 다양한 수준으로 팁에 결합하였다. 팁을 동일 농도의 다클론 Fab + 200 nM hACE2, 400 nM CR3022 또는 20 nM S309에 침지하여, 300-2000초간 인큐베이션하였다. 데이터에서 베이스라인을 제하고, Pall™ Forte Bio/Sartorius 분석 소프트웨어 (버전 12.0)로 다클론 Fab 프리-로딩에 대해 정렬하였으며, PRISM™에서 도표로 작성하였다.
SEQUENCE LISTING <110> University of Washington King, Neil P. Veesler, David Walkey, Carl Walls, Alexandra C. Wang, Jing Yang <120> Polypeptides, Compositions, and their Use to Treat or Limit Development of an Infection <130> 20-1008-PCT <150> 62/977036 <151> 2020-02-14 <150> 63/046159 <151> 2020-06-30 <160> 193 <170> PatentIn version 3.5 <210> 1 <211> 435 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 1 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 1 5 10 15 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 20 25 30 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 35 40 45 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 50 55 60 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 65 70 75 80 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 85 90 95 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 100 105 110 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 115 120 125 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 130 135 140 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 145 150 155 160 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 165 170 175 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 180 185 190 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Gly Gly Ser Gly 195 200 205 Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala 210 215 220 Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His 225 230 235 240 Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu 245 250 255 Lys Ala Val Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr 260 265 270 Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu 275 280 285 Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu 290 295 300 Gln Ala Arg Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro 305 310 315 320 His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe 325 330 335 Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys 340 345 350 Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro 355 360 365 Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val 370 375 380 Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala 385 390 395 400 Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro 405 410 415 Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly 420 425 430 Ala Thr Glu 435 <210> 2 <211> 463 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(28) <223> optionally absent <220> <221> MISC_FEATURE <222> (223)..(260) <223> optionally absent <400> 2 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Arg Phe Pro Asn 20 25 30 Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe 35 40 45 Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala 50 55 60 Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys 65 70 75 80 Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val 85 90 95 Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala 100 105 110 Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp 115 120 125 Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser 130 135 140 Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser 145 150 155 160 Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala 165 170 175 Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro 180 185 190 Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro 195 200 205 Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr 210 215 220 Val Cys Gly Pro Lys Lys Ser Thr Gly Gly Ser Gly Gly Ser Gly Ser 225 230 235 240 Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu 245 250 255 Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala 260 265 270 Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala 275 280 285 Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro 290 295 300 Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly 305 310 315 320 Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys 325 330 335 Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu 340 345 350 Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly 355 360 365 Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr 370 375 380 Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys 385 390 395 400 Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly 405 410 415 Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala 420 425 430 Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg 435 440 445 Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu 450 455 460 <210> 3 <211> 409 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (205)..(205) <223> X is absent or is an amino acid linker <400> 3 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 1 5 10 15 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 20 25 30 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 35 40 45 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 50 55 60 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 65 70 75 80 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 85 90 95 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 100 105 110 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 115 120 125 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 130 135 140 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 145 150 155 160 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 165 170 175 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 180 185 190 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Xaa Lys Met Glu 195 200 205 Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn Ser 210 215 220 Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val 225 230 235 240 His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile 245 250 255 Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly 260 265 270 Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala Val Glu Ser Gly Ala 275 280 285 Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala 290 295 300 Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu 305 310 315 320 Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro 325 330 335 Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe 340 345 350 Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val 355 360 365 Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala 370 375 380 Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe 385 390 395 400 Val Glu Lys Ile Arg Gly Ala Thr Glu 405 <210> 4 <211> 441 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (237)..(237) <223> X is absent or is an amino acid linker <400> 4 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 35 40 45 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 50 55 60 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 65 70 75 80 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 85 90 95 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 100 105 110 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 115 120 125 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 130 135 140 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 145 150 155 160 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 165 170 175 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 180 185 190 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 195 200 205 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 210 215 220 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Xaa Lys Met Glu 225 230 235 240 Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn Ser 245 250 255 Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val 260 265 270 His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile 275 280 285 Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly 290 295 300 Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala Val Glu Ser Gly Ala 305 310 315 320 Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala 325 330 335 Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu 340 345 350 Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro 355 360 365 Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe 370 375 380 Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val 385 390 395 400 Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala 405 410 415 Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe 420 425 430 Val Glu Lys Ile Arg Gly Ala Thr Glu 435 440 <210> 5 <211> 439 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (209)..(235) <223> optionally absent <400> 5 Glu Thr Gly Thr Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 1 5 10 15 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 20 25 30 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 35 40 45 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 50 55 60 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 65 70 75 80 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala 85 90 95 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 100 105 110 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 115 120 125 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 130 135 140 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 145 150 155 160 Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 165 170 175 Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 180 185 190 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 195 200 205 Gly Gly Ser Gly Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser 210 215 220 Glu Lys Ala Ala Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu Leu 225 230 235 240 Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu 245 250 255 Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val His Leu 260 265 270 Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala 275 280 285 Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val 290 295 300 Thr Ser Val Glu Gln Ala Arg Lys Ala Val Glu Ser Gly Ala Glu Phe 305 310 315 320 Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu 325 330 335 Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val 340 345 350 Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu 355 360 365 Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn 370 375 380 Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu 385 390 395 400 Trp Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val 405 410 415 Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu 420 425 430 Lys Ile Arg Gly Ala Thr Glu 435 <210> 6 <211> 467 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (237)..(263) <223> optionally absent <400> 6 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 35 40 45 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 50 55 60 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 65 70 75 80 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 85 90 95 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 100 105 110 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 115 120 125 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 130 135 140 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 145 150 155 160 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 165 170 175 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 180 185 190 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 195 200 205 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 210 215 220 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Gly Gly Ser Gly 225 230 235 240 Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala 245 250 255 Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His 260 265 270 Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu 275 280 285 Lys Ala Val Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr 290 295 300 Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu 305 310 315 320 Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu 325 330 335 Gln Ala Arg Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro 340 345 350 His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe 355 360 365 Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys 370 375 380 Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro 385 390 395 400 Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val 405 410 415 Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala 420 425 430 Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro 435 440 445 Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly 450 455 460 Ala Thr Glu 465 <210> 7 <211> 413 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (209)..(209) <223> X is absent or is an amino acid linker <400> 7 Glu Thr Gly Thr Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 1 5 10 15 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 20 25 30 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 35 40 45 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 50 55 60 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 65 70 75 80 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala 85 90 95 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 100 105 110 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 115 120 125 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 130 135 140 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 145 150 155 160 Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 165 170 175 Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 180 185 190 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 195 200 205 Xaa Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu 210 215 220 Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe 225 230 235 240 Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala 245 250 255 Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile 260 265 270 Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala Val 275 280 285 Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile 290 295 300 Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met 305 310 315 320 Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu 325 330 335 Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met 340 345 350 Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn 355 360 365 Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly 370 375 380 Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys 385 390 395 400 Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu 405 410 <210> 8 <211> 467 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (237)..(263) <223> optionally absent <400> 8 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 35 40 45 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 50 55 60 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 65 70 75 80 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 85 90 95 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 100 105 110 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 115 120 125 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 130 135 140 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 145 150 155 160 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 165 170 175 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 180 185 190 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 195 200 205 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 210 215 220 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Gly Gly Ser Gly 225 230 235 240 Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala 245 250 255 Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His 260 265 270 Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu 275 280 285 Lys Ala Val Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr 290 295 300 Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu 305 310 315 320 Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu 325 330 335 Gln Ala Arg Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro 340 345 350 His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe 355 360 365 Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys 370 375 380 Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro 385 390 395 400 Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val 405 410 415 Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala 420 425 430 Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro 435 440 445 Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly 450 455 460 Ala Thr Glu 465 <210> 9 <211> 478 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (237)..(263) <223> optionally absent <220> <221> MISC_FEATURE <222> (468)..(478) <223> optionally absent <400> 9 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 35 40 45 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 50 55 60 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 65 70 75 80 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 85 90 95 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 100 105 110 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 115 120 125 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 130 135 140 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 145 150 155 160 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 165 170 175 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 180 185 190 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 195 200 205 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 210 215 220 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Gly Gly Ser Gly 225 230 235 240 Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala 245 250 255 Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His 260 265 270 Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu 275 280 285 Lys Ala Val Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr 290 295 300 Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu 305 310 315 320 Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu 325 330 335 Gln Ala Arg Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro 340 345 350 His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe 355 360 365 Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys 370 375 380 Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro 385 390 395 400 Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val 405 410 415 Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala 420 425 430 Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro 435 440 445 Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly 450 455 460 Ala Thr Glu Gly Gly Ser His His His His His His His His 465 470 475 <210> 10 <211> 450 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (209)..(235) <223> optionally absent <220> <221> MISC_FEATURE <222> (440)..(450) <223> optionally absent <400> 10 Glu Thr Gly Thr Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 1 5 10 15 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 20 25 30 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 35 40 45 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 50 55 60 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 65 70 75 80 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala 85 90 95 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 100 105 110 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 115 120 125 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 130 135 140 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 145 150 155 160 Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 165 170 175 Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 180 185 190 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 195 200 205 Gly Gly Ser Gly Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser 210 215 220 Glu Lys Ala Ala Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu Leu 225 230 235 240 Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu 245 250 255 Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val His Leu 260 265 270 Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala 275 280 285 Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val 290 295 300 Thr Ser Val Glu Gln Ala Arg Lys Ala Val Glu Ser Gly Ala Glu Phe 305 310 315 320 Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu 325 330 335 Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val 340 345 350 Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu 355 360 365 Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn 370 375 380 Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu 385 390 395 400 Trp Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val 405 410 415 Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu 420 425 430 Lys Ile Arg Gly Ala Thr Glu Gly Gly Ser His His His His His His 435 440 445 His His 450 <210> 11 <211> 452 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (237)..(237) <223> X is absent or is an amino acid linker <220> <221> MISC_FEATURE <222> (442)..(452) <223> optionally absent <400> 11 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 35 40 45 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 50 55 60 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 65 70 75 80 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 85 90 95 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 100 105 110 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 115 120 125 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 130 135 140 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 145 150 155 160 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 165 170 175 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 180 185 190 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 195 200 205 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 210 215 220 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Xaa Lys Met Glu 225 230 235 240 Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn Ser 245 250 255 Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val 260 265 270 His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile 275 280 285 Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly 290 295 300 Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala Val Glu Ser Gly Ala 305 310 315 320 Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala 325 330 335 Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu 340 345 350 Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro 355 360 365 Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe 370 375 380 Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val 385 390 395 400 Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala 405 410 415 Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe 420 425 430 Val Glu Lys Ile Arg Gly Ala Thr Glu Gly Gly Ser His His His His 435 440 445 His His His His 450 <210> 12 <211> 424 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (209)..(209) <223> X is absent or is an amino acid linker <220> <221> MISC_FEATURE <222> (414)..(424) <223> optionally absent <400> 12 Glu Thr Gly Thr Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 1 5 10 15 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 20 25 30 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 35 40 45 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 50 55 60 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 65 70 75 80 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala 85 90 95 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 100 105 110 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 115 120 125 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 130 135 140 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 145 150 155 160 Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 165 170 175 Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 180 185 190 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 195 200 205 Xaa Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu 210 215 220 Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe 225 230 235 240 Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala 245 250 255 Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile 260 265 270 Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala Val 275 280 285 Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile 290 295 300 Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met 305 310 315 320 Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu 325 330 335 Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met 340 345 350 Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn 355 360 365 Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly 370 375 380 Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys 385 390 395 400 Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu Gly Gly Ser 405 410 415 His His His His His His His His 420 <210> 13 <211> 427 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 13 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 1 5 10 15 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 20 25 30 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 35 40 45 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 50 55 60 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 65 70 75 80 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 85 90 95 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 100 105 110 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 115 120 125 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 130 135 140 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 145 150 155 160 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 165 170 175 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 180 185 190 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Gly Gly Ser Gly 195 200 205 Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu Ala Ala Arg Lys 210 215 220 Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala 225 230 235 240 Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly 245 250 255 Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr 260 265 270 Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly 275 280 285 Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala Val Glu Ser 290 295 300 Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln 305 310 315 320 Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro 325 330 335 Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu 340 345 350 Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly 355 360 365 Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp 370 375 380 Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly 385 390 395 400 Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys 405 410 415 Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu 420 425 <210> 14 <211> 470 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (460)..(470) <223> optionally absent <400> 14 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 35 40 45 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 50 55 60 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 65 70 75 80 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 85 90 95 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 100 105 110 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 115 120 125 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 130 135 140 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 145 150 155 160 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 165 170 175 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 180 185 190 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 195 200 205 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 210 215 220 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Gly Gly Ser Gly 225 230 235 240 Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu Ala Ala Arg Lys 245 250 255 Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala 260 265 270 Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly 275 280 285 Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr 290 295 300 Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly 305 310 315 320 Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala Val Glu Ser 325 330 335 Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln 340 345 350 Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro 355 360 365 Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu 370 375 380 Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly 385 390 395 400 Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp 405 410 415 Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly 420 425 430 Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys 435 440 445 Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu Gly Gly Ser His His 450 455 460 His His His His His His 465 470 <210> 15 <211> 431 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 15 Glu Thr Gly Thr Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 1 5 10 15 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 20 25 30 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 35 40 45 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 50 55 60 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 65 70 75 80 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala 85 90 95 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 100 105 110 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 115 120 125 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 130 135 140 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 145 150 155 160 Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 165 170 175 Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 180 185 190 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 195 200 205 Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu 210 215 220 Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala 225 230 235 240 Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala 245 250 255 Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro 260 265 270 Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly 275 280 285 Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys 290 295 300 Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu 305 310 315 320 Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly 325 330 335 Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr 340 345 350 Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys 355 360 365 Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly 370 375 380 Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala 385 390 395 400 Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg 405 410 415 Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu 420 425 430 <210> 16 <211> 442 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (432)..(442) <223> optionally absent <400> 16 Glu Thr Gly Thr Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 1 5 10 15 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 20 25 30 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 35 40 45 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 50 55 60 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 65 70 75 80 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala 85 90 95 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 100 105 110 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 115 120 125 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 130 135 140 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 145 150 155 160 Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 165 170 175 Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 180 185 190 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 195 200 205 Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu 210 215 220 Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala 225 230 235 240 Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala 245 250 255 Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro 260 265 270 Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly 275 280 285 Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys 290 295 300 Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu 305 310 315 320 Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly 325 330 335 Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr 340 345 350 Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys 355 360 365 Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly 370 375 380 Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala 385 390 395 400 Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg 405 410 415 Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu Gly 420 425 430 Gly Ser His His His His His His His His 435 440 <210> 17 <211> 408 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 17 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 1 5 10 15 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 20 25 30 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 35 40 45 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 50 55 60 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 65 70 75 80 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 85 90 95 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 100 105 110 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 115 120 125 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 130 135 140 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 145 150 155 160 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 165 170 175 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 180 185 190 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Lys Met Glu Glu 195 200 205 Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val 210 215 220 Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val His 225 230 235 240 Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys 245 250 255 Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr 260 265 270 Val Thr Ser Val Glu Gln Ala Arg Lys Ala Val Glu Ser Gly Ala Glu 275 280 285 Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys 290 295 300 Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu 305 310 315 320 Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly 325 330 335 Glu Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro 340 345 350 Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala 355 360 365 Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu 370 375 380 Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val 385 390 395 400 Glu Lys Ile Arg Gly Ala Thr Glu 405 <210> 18 <211> 452 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (237)..(237) <223> X is absent or is an amino acid linker <220> <221> MISC_FEATURE <222> (442)..(452) <223> optionally absent <400> 18 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 35 40 45 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 50 55 60 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 65 70 75 80 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 85 90 95 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 100 105 110 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 115 120 125 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 130 135 140 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 145 150 155 160 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 165 170 175 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 180 185 190 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 195 200 205 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 210 215 220 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Xaa Lys Met Glu 225 230 235 240 Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn Ser 245 250 255 Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val 260 265 270 His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile 275 280 285 Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly 290 295 300 Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala Val Glu Ser Gly Ala 305 310 315 320 Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala 325 330 335 Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu 340 345 350 Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro 355 360 365 Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe 370 375 380 Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val 385 390 395 400 Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala 405 410 415 Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe 420 425 430 Val Glu Lys Ile Arg Gly Ala Thr Glu Gly Gly Ser His His His His 435 440 445 His His His His 450 <210> 19 <211> 413 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (209)..(209) <223> X is absent or is an amino acid linker <400> 19 Glu Thr Gly Thr Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 1 5 10 15 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 20 25 30 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 35 40 45 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 50 55 60 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 65 70 75 80 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala 85 90 95 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 100 105 110 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 115 120 125 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 130 135 140 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 145 150 155 160 Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 165 170 175 Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 180 185 190 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 195 200 205 Xaa Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu 210 215 220 Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe 225 230 235 240 Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala 245 250 255 Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile 260 265 270 Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala Val 275 280 285 Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile 290 295 300 Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met 305 310 315 320 Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu 325 330 335 Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met 340 345 350 Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn 355 360 365 Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly 370 375 380 Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys 385 390 395 400 Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu 405 410 <210> 20 <211> 424 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (209)..(209) <223> X is absent or is an amino acid linker <220> <221> MISC_FEATURE <222> (414)..(424) <223> optionally absent <400> 20 Glu Thr Gly Thr Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 1 5 10 15 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 20 25 30 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 35 40 45 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 50 55 60 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 65 70 75 80 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala 85 90 95 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 100 105 110 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 115 120 125 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 130 135 140 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 145 150 155 160 Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 165 170 175 Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 180 185 190 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 195 200 205 Xaa Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu 210 215 220 Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe 225 230 235 240 Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala 245 250 255 Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile 260 265 270 Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala Val 275 280 285 Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile 290 295 300 Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met 305 310 315 320 Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu 325 330 335 Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met 340 345 350 Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn 355 360 365 Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly 370 375 380 Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys 385 390 395 400 Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu Gly Gly Ser 405 410 415 His His His His His His His His 420 <210> 21 <211> 430 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 21 Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala 1 5 10 15 Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn 20 25 30 Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr 35 40 45 Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe 50 55 60 Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg 65 70 75 80 Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys 85 90 95 Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn 100 105 110 Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe 115 120 125 Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile 130 135 140 Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys 145 150 155 160 Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly 165 170 175 Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala 180 185 190 Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Gly Ser Gly Ser Gly 195 200 205 Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu Ala 210 215 220 Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val 225 230 235 240 Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val 245 250 255 Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp 260 265 270 Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala 275 280 285 Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala 290 295 300 Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu 305 310 315 320 Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val 325 330 335 Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile 340 345 350 Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala 355 360 365 Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val 370 375 380 Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val 385 390 395 400 Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu 405 410 415 Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu 420 425 430 <210> 22 <211> 474 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (464)..(474) <223> optionally absent <400> 22 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 35 40 45 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 50 55 60 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 65 70 75 80 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 85 90 95 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 100 105 110 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 115 120 125 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 130 135 140 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 145 150 155 160 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 165 170 175 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 180 185 190 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 195 200 205 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 210 215 220 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Gly Ser Gly Ser 225 230 235 240 Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu 245 250 255 Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala 260 265 270 Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala 275 280 285 Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro 290 295 300 Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly 305 310 315 320 Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys 325 330 335 Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu 340 345 350 Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly 355 360 365 Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr 370 375 380 Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys 385 390 395 400 Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly 405 410 415 Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala 420 425 430 Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg 435 440 445 Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu Gly 450 455 460 Gly Ser His His His His His His His His 465 470 <210> 23 <211> 435 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 23 Glu Thr Gly Thr Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 1 5 10 15 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 20 25 30 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 35 40 45 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 50 55 60 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 65 70 75 80 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala 85 90 95 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 100 105 110 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 115 120 125 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 130 135 140 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 145 150 155 160 Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 165 170 175 Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 180 185 190 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 195 200 205 Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala 210 215 220 Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His 225 230 235 240 Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu 245 250 255 Lys Ala Val Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr 260 265 270 Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu 275 280 285 Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu 290 295 300 Gln Ala Arg Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro 305 310 315 320 His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe 325 330 335 Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys 340 345 350 Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro 355 360 365 Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val 370 375 380 Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala 385 390 395 400 Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro 405 410 415 Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly 420 425 430 Ala Thr Glu 435 <210> 24 <211> 446 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (436)..(446) <223> optionally absent <400> 24 Glu Thr Gly Thr Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 1 5 10 15 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 20 25 30 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 35 40 45 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 50 55 60 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 65 70 75 80 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala 85 90 95 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 100 105 110 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 115 120 125 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 130 135 140 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 145 150 155 160 Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 165 170 175 Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 180 185 190 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 195 200 205 Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala 210 215 220 Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His 225 230 235 240 Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu 245 250 255 Lys Ala Val Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr 260 265 270 Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu 275 280 285 Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu 290 295 300 Gln Ala Arg Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro 305 310 315 320 His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe 325 330 335 Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys 340 345 350 Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro 355 360 365 Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val 370 375 380 Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala 385 390 395 400 Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro 405 410 415 Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly 420 425 430 Ala Thr Glu Gly Gly Ser His His His His His His His His 435 440 445 <210> 25 <211> 409 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (205)..(205) <223> X is absent or is an amino acid linker <400> 25 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 1 5 10 15 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 20 25 30 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 35 40 45 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 50 55 60 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 65 70 75 80 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 85 90 95 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 100 105 110 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 115 120 125 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 130 135 140 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 145 150 155 160 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 165 170 175 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 180 185 190 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Xaa Lys Met Glu 195 200 205 Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn Ser 210 215 220 Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val 225 230 235 240 His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile 245 250 255 Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly 260 265 270 Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala Val Glu Ser Gly Ala 275 280 285 Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala 290 295 300 Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu 305 310 315 320 Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro 325 330 335 Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe 340 345 350 Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val 355 360 365 Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala 370 375 380 Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe 385 390 395 400 Val Glu Lys Ile Arg Gly Ala Thr Glu 405 <210> 26 <211> 452 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (237)..(237) <223> X is absent or is an amino acid linker <220> <221> MISC_FEATURE <222> (442)..(452) <223> optionally absent <400> 26 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 35 40 45 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 50 55 60 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 65 70 75 80 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 85 90 95 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 100 105 110 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 115 120 125 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 130 135 140 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 145 150 155 160 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 165 170 175 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 180 185 190 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 195 200 205 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 210 215 220 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Xaa Lys Met Glu 225 230 235 240 Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn Ser 245 250 255 Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val 260 265 270 His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile 275 280 285 Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly 290 295 300 Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala Val Glu Ser Gly Ala 305 310 315 320 Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala 325 330 335 Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu 340 345 350 Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro 355 360 365 Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe 370 375 380 Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val 385 390 395 400 Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala 405 410 415 Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe 420 425 430 Val Glu Lys Ile Arg Gly Ala Thr Glu Gly Gly Ser His His His His 435 440 445 His His His His 450 <210> 27 <211> 413 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (209)..(209) <223> X is absent or is an amino acid linker <400> 27 Glu Thr Gly Thr Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 1 5 10 15 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 20 25 30 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 35 40 45 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 50 55 60 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 65 70 75 80 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala 85 90 95 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 100 105 110 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 115 120 125 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 130 135 140 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 145 150 155 160 Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 165 170 175 Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 180 185 190 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 195 200 205 Xaa Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu 210 215 220 Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe 225 230 235 240 Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala 245 250 255 Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile 260 265 270 Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala Val 275 280 285 Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile 290 295 300 Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met 305 310 315 320 Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu 325 330 335 Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met 340 345 350 Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn 355 360 365 Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly 370 375 380 Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys 385 390 395 400 Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu 405 410 <210> 28 <211> 424 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (209)..(209) <223> X is absent or is an amino acid linker <220> <221> MISC_FEATURE <222> (414)..(424) <223> optionally absent <400> 28 Glu Thr Gly Thr Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 1 5 10 15 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 20 25 30 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 35 40 45 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 50 55 60 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 65 70 75 80 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala 85 90 95 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 100 105 110 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 115 120 125 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 130 135 140 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 145 150 155 160 Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 165 170 175 Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 180 185 190 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 195 200 205 Xaa Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu 210 215 220 Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe 225 230 235 240 Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala 245 250 255 Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile 260 265 270 Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala Val 275 280 285 Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile 290 295 300 Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met 305 310 315 320 Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu 325 330 335 Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met 340 345 350 Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn 355 360 365 Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly 370 375 380 Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys 385 390 395 400 Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu Gly Gly Ser 405 410 415 His His His His His His His His 420 <210> 29 <211> 1468 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 29 Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr 1 5 10 15 Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser 20 25 30 Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn 35 40 45 Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys 50 55 60 Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala 65 70 75 80 Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr 85 90 95 Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn 100 105 110 Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln 145 150 155 160 Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu 165 170 175 Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser 180 185 190 Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser 195 200 205 Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg 210 215 220 Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp 225 230 235 240 Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr 245 250 255 Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile 260 265 270 Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 275 280 285 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 290 295 300 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 305 310 315 320 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 325 330 335 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 340 345 350 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 355 360 365 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 370 375 380 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 385 390 395 400 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 405 410 415 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 420 425 430 Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu 435 440 445 Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser 450 455 460 Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln 465 470 475 480 Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys 530 535 540 Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Ser Gly Ala Gly 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Gly Ser Gly Arg Glu 1190 1195 1200 Asn Leu Tyr Phe Gln Gly Gly Gly Gly Ser Gly Tyr Ile Pro Glu 1205 1210 1215 Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp 1220 1225 1230 Val Leu Leu Ser Thr Phe Leu Gly Gly Ser Gly Ser Gly Gly Ser 1235 1240 1245 Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu Ala Ala 1250 1255 1260 Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val 1265 1270 1275 Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala 1280 1285 1290 Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val 1295 1300 1305 Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu 1310 1315 1320 Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln 1325 1330 1335 Ala Arg Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro 1340 1345 1350 His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val 1355 1360 1365 Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala 1370 1375 1380 Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val 1385 1390 1395 Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn 1400 1405 1410 Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala 1415 1420 1425 Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala 1430 1435 1440 Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala 1445 1450 1455 Phe Val Glu Lys Ile Arg Gly Ala Thr Glu 1460 1465 <210> 30 <211> 1511 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (1501)..(1511) <223> optionally absent <400> 30 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr 35 40 45 Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser 50 55 60 Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn 65 70 75 80 Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys 85 90 95 Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala 100 105 110 Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr 115 120 125 Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn 130 135 140 Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu 145 150 155 160 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 165 170 175 Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln 180 185 190 Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu 195 200 205 Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser 210 215 220 Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser 225 230 235 240 Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg 245 250 255 Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp 260 265 270 Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr 275 280 285 Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile 290 295 300 Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 305 310 315 320 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 325 330 335 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 340 345 350 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 355 360 365 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 370 375 380 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 385 390 395 400 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 405 410 415 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 420 425 430 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 435 440 445 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 450 455 460 Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu 465 470 475 480 Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser 485 490 495 Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln 500 505 510 Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg 515 520 525 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 530 535 540 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 545 550 555 560 Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys 565 570 575 Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr 580 585 590 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 595 600 605 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 610 615 620 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 625 630 635 640 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 645 650 655 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 660 665 670 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 675 680 685 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Ser Gly Ala Gly 690 695 700 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 705 710 715 720 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 725 730 735 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 740 745 750 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 755 760 765 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 770 775 780 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 785 790 795 800 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 805 810 815 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 820 825 830 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 835 840 845 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 850 855 860 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 865 870 875 880 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 885 890 895 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 900 905 910 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 915 920 925 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 930 935 940 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 945 950 955 960 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 965 970 975 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 980 985 990 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 995 1000 1005 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu 1010 1015 1020 Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg 1025 1030 1035 Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu 1040 1045 1050 Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu 1055 1060 1065 Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His 1070 1075 1080 Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro 1085 1090 1095 Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val 1100 1105 1110 Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe 1115 1120 1125 Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly 1130 1135 1140 Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp 1145 1150 1155 Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys 1160 1165 1170 Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile 1175 1180 1185 Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp 1190 1195 1200 Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp 1205 1210 1215 Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Gly Ser Gly 1220 1225 1230 Arg Glu Asn Leu Tyr Phe Gln Gly Gly Gly Gly Ser Gly Tyr Ile 1235 1240 1245 Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly 1250 1255 1260 Glu Trp Val Leu Leu Ser Thr Phe Leu Gly Gly Ser Gly Ser Gly 1265 1270 1275 Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu 1280 1285 1290 Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val 1295 1300 1305 Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala 1310 1315 1320 Val Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe 1325 1330 1335 Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu 1340 1345 1350 Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val 1355 1360 1365 Glu Gln Ala Arg Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val 1370 1375 1380 Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Lys 1385 1390 1395 Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val 1400 1405 1410 Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly 1415 1420 1425 Glu Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe 1430 1435 1440 Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn 1445 1450 1455 Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly 1460 1465 1470 Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala 1475 1480 1485 Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu Gly Gly Ser 1490 1495 1500 His His His His His His His His 1505 1510 <210> 31 <211> 1472 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 31 Glu Thr Gly Thr Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro 1 5 10 15 Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys 20 25 30 Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro 35 40 45 Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr 50 55 60 Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly 65 70 75 80 Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile 85 90 95 Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn 100 105 110 Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn 115 120 125 Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met 130 135 140 Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu 145 150 155 160 Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn 165 170 175 Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe 180 185 190 Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro 195 200 205 Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile 210 215 220 Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu 225 230 235 240 Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr 245 250 255 Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu 260 265 270 Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser 275 280 285 Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr 290 295 300 Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe 305 310 315 320 Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr 325 330 335 Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys 340 345 350 Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe 355 360 365 Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr 370 375 380 Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln 385 390 395 400 Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu 405 410 415 Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu 420 425 430 Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg 435 440 445 Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr 450 455 460 Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr 465 470 475 480 Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr 485 490 495 Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro 500 505 510 Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys 515 520 525 Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr 530 535 540 Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile 545 550 555 560 Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu 565 570 575 Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly 580 585 590 Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys 595 600 605 Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp 610 615 620 Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys 625 630 635 640 Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro 645 650 655 Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro 660 665 670 Ser Gly Ala Gly Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met 675 680 685 Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala 690 695 700 Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val 705 710 715 720 Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp 725 730 735 Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr 740 745 750 Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn 755 760 765 Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro 770 775 780 Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro 785 790 795 800 Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys 805 810 815 Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu 820 825 830 Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly 835 840 845 Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr 850 855 860 Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly 865 870 875 880 Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg 885 890 895 Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys 900 905 910 Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser 915 920 925 Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn 930 935 940 Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn 945 950 955 960 Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp 965 970 975 Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu 980 985 990 Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu 995 1000 1005 Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys 1010 1015 1020 Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr 1025 1030 1035 His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe 1040 1045 1050 Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr 1055 1060 1065 Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu 1070 1075 1080 Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg 1085 1090 1095 Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val 1100 1105 1110 Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val 1115 1120 1125 Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu 1130 1135 1140 Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly 1145 1150 1155 Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu 1160 1165 1170 Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu 1175 1180 1185 Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Gly 1190 1195 1200 Ser Gly Arg Glu Asn Leu Tyr Phe Gln Gly Gly Gly Gly Ser Gly 1205 1210 1215 Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys 1220 1225 1230 Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu Gly Gly Ser Gly 1235 1240 1245 Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala 1250 1255 1260 Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys 1265 1270 1275 Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu 1280 1285 1290 Lys Ala Val Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile 1295 1300 1305 Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser 1310 1315 1320 Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr 1325 1330 1335 Ser Val Glu Gln Ala Arg Lys Ala Val Glu Ser Gly Ala Glu Phe 1340 1345 1350 Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys 1355 1360 1365 Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu 1370 1375 1380 Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe 1385 1390 1395 Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly 1400 1405 1410 Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu 1415 1420 1425 Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly 1430 1435 1440 Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu 1445 1450 1455 Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu 1460 1465 1470 <210> 32 <211> 1483 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1473)..(1483) <223> optionally absent <400> 32 Glu Thr Gly Thr Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro 1 5 10 15 Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys 20 25 30 Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro 35 40 45 Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr 50 55 60 Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly 65 70 75 80 Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile 85 90 95 Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn 100 105 110 Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn 115 120 125 Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met 130 135 140 Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu 145 150 155 160 Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn 165 170 175 Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe 180 185 190 Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro 195 200 205 Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile 210 215 220 Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu 225 230 235 240 Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr 245 250 255 Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu 260 265 270 Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser 275 280 285 Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr 290 295 300 Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe 305 310 315 320 Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr 325 330 335 Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys 340 345 350 Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe 355 360 365 Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr 370 375 380 Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln 385 390 395 400 Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu 405 410 415 Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu 420 425 430 Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg 435 440 445 Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr 450 455 460 Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr 465 470 475 480 Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr 485 490 495 Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro 500 505 510 Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys 515 520 525 Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr 530 535 540 Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile 545 550 555 560 Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu 565 570 575 Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly 580 585 590 Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys 595 600 605 Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp 610 615 620 Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys 625 630 635 640 Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro 645 650 655 Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro 660 665 670 Ser Gly Ala Gly Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met 675 680 685 Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala 690 695 700 Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val 705 710 715 720 Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp 725 730 735 Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr 740 745 750 Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn 755 760 765 Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro 770 775 780 Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro 785 790 795 800 Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys 805 810 815 Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu 820 825 830 Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly 835 840 845 Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr 850 855 860 Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly 865 870 875 880 Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg 885 890 895 Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys 900 905 910 Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser 915 920 925 Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn 930 935 940 Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn 945 950 955 960 Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp 965 970 975 Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu 980 985 990 Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu 995 1000 1005 Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys 1010 1015 1020 Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr 1025 1030 1035 His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe 1040 1045 1050 Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr 1055 1060 1065 Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu 1070 1075 1080 Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg 1085 1090 1095 Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val 1100 1105 1110 Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val 1115 1120 1125 Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu 1130 1135 1140 Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly 1145 1150 1155 Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu 1160 1165 1170 Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu 1175 1180 1185 Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Gly 1190 1195 1200 Ser Gly Arg Glu Asn Leu Tyr Phe Gln Gly Gly Gly Gly Ser Gly 1205 1210 1215 Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys 1220 1225 1230 Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu Gly Gly Ser Gly 1235 1240 1245 Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala 1250 1255 1260 Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys 1265 1270 1275 Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu 1280 1285 1290 Lys Ala Val Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile 1295 1300 1305 Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser 1310 1315 1320 Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr 1325 1330 1335 Ser Val Glu Gln Ala Arg Lys Ala Val Glu Ser Gly Ala Glu Phe 1340 1345 1350 Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys 1355 1360 1365 Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu 1370 1375 1380 Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe 1385 1390 1395 Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly 1400 1405 1410 Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu 1415 1420 1425 Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly 1430 1435 1440 Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu 1445 1450 1455 Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu Gly 1460 1465 1470 Gly Ser His His His His His His His His 1475 1480 <210> 33 <211> 1446 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1242)..(1242) <223> X is absent or is an amino acid linker <400> 33 Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr 1 5 10 15 Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser 20 25 30 Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn 35 40 45 Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys 50 55 60 Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala 65 70 75 80 Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr 85 90 95 Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn 100 105 110 Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln 145 150 155 160 Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu 165 170 175 Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser 180 185 190 Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser 195 200 205 Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg 210 215 220 Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp 225 230 235 240 Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr 245 250 255 Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile 260 265 270 Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 275 280 285 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 290 295 300 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 305 310 315 320 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 325 330 335 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 340 345 350 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 355 360 365 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 370 375 380 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 385 390 395 400 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 405 410 415 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 420 425 430 Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu 435 440 445 Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser 450 455 460 Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln 465 470 475 480 Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys 530 535 540 Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Ser Gly Ala Gly 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Gly Ser Gly Arg Glu 1190 1195 1200 Asn Leu Tyr Phe Gln Gly Gly Gly Gly Ser Gly Tyr Ile Pro Glu 1205 1210 1215 Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp 1220 1225 1230 Val Leu Leu Ser Thr Phe Leu Gly Xaa Lys Met Glu Glu Leu Phe 1235 1240 1245 Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu 1250 1255 1260 Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val His 1265 1270 1275 Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile 1280 1285 1290 Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala 1295 1300 1305 Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala Val Glu Ser 1310 1315 1320 Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser 1325 1330 1335 Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met 1340 1345 1350 Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile 1355 1360 1365 Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys 1370 1375 1380 Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly 1385 1390 1395 Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val 1400 1405 1410 Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp 1415 1420 1425 Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly 1430 1435 1440 Ala Thr Glu 1445 <210> 34 <211> 1489 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (1274)..(1274) <223> X is absent or is an amino acid linker <220> <221> MISC_FEATURE <222> (1480)..(1490) <223> optionally absent <400> 34 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr 35 40 45 Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser 50 55 60 Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn 65 70 75 80 Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys 85 90 95 Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala 100 105 110 Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr 115 120 125 Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn 130 135 140 Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu 145 150 155 160 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 165 170 175 Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln 180 185 190 Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu 195 200 205 Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser 210 215 220 Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser 225 230 235 240 Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg 245 250 255 Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp 260 265 270 Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr 275 280 285 Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile 290 295 300 Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 305 310 315 320 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 325 330 335 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 340 345 350 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 355 360 365 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 370 375 380 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 385 390 395 400 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 405 410 415 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 420 425 430 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 435 440 445 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 450 455 460 Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu 465 470 475 480 Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser 485 490 495 Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln 500 505 510 Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg 515 520 525 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 530 535 540 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 545 550 555 560 Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys 565 570 575 Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr 580 585 590 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 595 600 605 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 610 615 620 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 625 630 635 640 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 645 650 655 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 660 665 670 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 675 680 685 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Ser Gly Ala Gly 690 695 700 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 705 710 715 720 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 725 730 735 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 740 745 750 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 755 760 765 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 770 775 780 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 785 790 795 800 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 805 810 815 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 820 825 830 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 835 840 845 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 850 855 860 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 865 870 875 880 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 885 890 895 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 900 905 910 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 915 920 925 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 930 935 940 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 945 950 955 960 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 965 970 975 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 980 985 990 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 995 1000 1005 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu 1010 1015 1020 Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg 1025 1030 1035 Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu 1040 1045 1050 Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu 1055 1060 1065 Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His 1070 1075 1080 Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro 1085 1090 1095 Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val 1100 1105 1110 Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe 1115 1120 1125 Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly 1130 1135 1140 Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp 1145 1150 1155 Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys 1160 1165 1170 Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile 1175 1180 1185 Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp 1190 1195 1200 Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp 1205 1210 1215 Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Gly Ser Gly 1220 1225 1230 Arg Glu Asn Leu Tyr Phe Gln Gly Gly Gly Gly Ser Gly Tyr Ile 1235 1240 1245 Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly 1250 1255 1260 Glu Trp Val Leu Leu Ser Thr Phe Leu Gly Xaa Lys Met Glu Glu 1265 1270 1275 Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn Ser 1280 1285 1290 Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly 1295 1300 1305 Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr 1310 1315 1320 Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile 1325 1330 1335 Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala Val 1340 1345 1350 Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu 1355 1360 1365 Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly 1370 1375 1380 Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His 1385 1390 1395 Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe 1400 1405 1410 Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro 1415 1420 1425 Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala 1430 1435 1440 Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr 1445 1450 1455 Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile 1460 1465 1470 Arg Gly Ala Thr Glu Gly Gly Ser His His His His His His His 1475 1480 1485 His <210> 35 <211> 1450 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1246)..(1246) <223> X is absent or is an amino acid linker <400> 35 Glu Thr Gly Thr Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro 1 5 10 15 Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys 20 25 30 Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro 35 40 45 Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr 50 55 60 Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly 65 70 75 80 Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile 85 90 95 Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn 100 105 110 Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn 115 120 125 Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met 130 135 140 Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu 145 150 155 160 Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn 165 170 175 Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe 180 185 190 Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro 195 200 205 Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile 210 215 220 Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu 225 230 235 240 Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr 245 250 255 Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu 260 265 270 Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser 275 280 285 Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr 290 295 300 Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe 305 310 315 320 Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr 325 330 335 Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys 340 345 350 Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe 355 360 365 Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr 370 375 380 Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln 385 390 395 400 Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu 405 410 415 Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu 420 425 430 Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg 435 440 445 Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr 450 455 460 Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr 465 470 475 480 Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr 485 490 495 Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro 500 505 510 Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys 515 520 525 Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr 530 535 540 Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile 545 550 555 560 Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu 565 570 575 Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly 580 585 590 Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys 595 600 605 Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp 610 615 620 Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys 625 630 635 640 Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro 645 650 655 Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro 660 665 670 Ser Gly Ala Gly Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met 675 680 685 Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala 690 695 700 Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val 705 710 715 720 Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp 725 730 735 Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr 740 745 750 Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn 755 760 765 Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro 770 775 780 Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro 785 790 795 800 Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys 805 810 815 Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu 820 825 830 Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly 835 840 845 Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr 850 855 860 Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly 865 870 875 880 Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg 885 890 895 Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys 900 905 910 Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser 915 920 925 Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn 930 935 940 Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn 945 950 955 960 Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp 965 970 975 Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu 980 985 990 Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu 995 1000 1005 Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys 1010 1015 1020 Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr 1025 1030 1035 His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe 1040 1045 1050 Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr 1055 1060 1065 Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu 1070 1075 1080 Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg 1085 1090 1095 Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val 1100 1105 1110 Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val 1115 1120 1125 Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu 1130 1135 1140 Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly 1145 1150 1155 Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu 1160 1165 1170 Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu 1175 1180 1185 Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Gly 1190 1195 1200 Ser Gly Arg Glu Asn Leu Tyr Phe Gln Gly Gly Gly Gly Ser Gly 1205 1210 1215 Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys 1220 1225 1230 Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu Gly Xaa Lys Met 1235 1240 1245 Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala 1250 1255 1260 Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala 1265 1270 1275 Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala 1280 1285 1290 Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala 1295 1300 1305 Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys 1310 1315 1320 Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp 1325 1330 1335 Glu Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met 1340 1345 1350 Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu 1355 1360 1365 Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro 1370 1375 1380 Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe 1385 1390 1395 Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe 1400 1405 1410 Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys 1415 1420 1425 Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu 1430 1435 1440 Lys Ile Arg Gly Ala Thr Glu 1445 1450 <210> 36 <211> 1461 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1246)..(1246) <223> X is absent or is an amino acid linker <220> <221> MISC_FEATURE <222> (1451)..(1461) <223> optionally absent <400> 36 Glu Thr Gly Thr Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro 1 5 10 15 Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys 20 25 30 Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro 35 40 45 Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr 50 55 60 Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly 65 70 75 80 Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile 85 90 95 Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn 100 105 110 Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn 115 120 125 Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met 130 135 140 Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu 145 150 155 160 Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn 165 170 175 Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe 180 185 190 Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro 195 200 205 Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile 210 215 220 Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu 225 230 235 240 Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr 245 250 255 Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu 260 265 270 Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser 275 280 285 Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr 290 295 300 Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe 305 310 315 320 Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr 325 330 335 Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys 340 345 350 Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe 355 360 365 Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr 370 375 380 Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln 385 390 395 400 Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu 405 410 415 Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu 420 425 430 Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg 435 440 445 Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr 450 455 460 Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr 465 470 475 480 Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr 485 490 495 Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro 500 505 510 Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys 515 520 525 Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr 530 535 540 Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile 545 550 555 560 Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu 565 570 575 Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly 580 585 590 Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys 595 600 605 Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp 610 615 620 Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys 625 630 635 640 Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro 645 650 655 Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro 660 665 670 Ser Gly Ala Gly Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met 675 680 685 Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala 690 695 700 Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val 705 710 715 720 Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp 725 730 735 Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr 740 745 750 Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn 755 760 765 Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro 770 775 780 Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro 785 790 795 800 Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys 805 810 815 Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu 820 825 830 Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly 835 840 845 Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr 850 855 860 Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly 865 870 875 880 Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg 885 890 895 Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys 900 905 910 Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser 915 920 925 Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn 930 935 940 Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn 945 950 955 960 Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp 965 970 975 Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu 980 985 990 Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu 995 1000 1005 Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys 1010 1015 1020 Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr 1025 1030 1035 His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe 1040 1045 1050 Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr 1055 1060 1065 Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu 1070 1075 1080 Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg 1085 1090 1095 Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val 1100 1105 1110 Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val 1115 1120 1125 Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu 1130 1135 1140 Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly 1145 1150 1155 Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu 1160 1165 1170 Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu 1175 1180 1185 Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Gly 1190 1195 1200 Ser Gly Arg Glu Asn Leu Tyr Phe Gln Gly Gly Gly Gly Ser Gly 1205 1210 1215 Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys 1220 1225 1230 Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu Gly Xaa Lys Met 1235 1240 1245 Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala 1250 1255 1260 Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala 1265 1270 1275 Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala 1280 1285 1290 Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala 1295 1300 1305 Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys 1310 1315 1320 Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp 1325 1330 1335 Glu Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met 1340 1345 1350 Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu 1355 1360 1365 Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro 1370 1375 1380 Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe 1385 1390 1395 Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe 1400 1405 1410 Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys 1415 1420 1425 Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu 1430 1435 1440 Lys Ile Arg Gly Ala Thr Glu Gly Gly Ser His His His His His 1445 1450 1455 His His His 1460 <210> 37 <211> 1425 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 37 Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr 1 5 10 15 Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser 20 25 30 Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn 35 40 45 Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys 50 55 60 Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala 65 70 75 80 Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr 85 90 95 Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn 100 105 110 Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln 145 150 155 160 Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu 165 170 175 Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser 180 185 190 Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser 195 200 205 Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg 210 215 220 Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp 225 230 235 240 Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr 245 250 255 Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile 260 265 270 Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 275 280 285 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 290 295 300 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 305 310 315 320 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 325 330 335 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 340 345 350 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 355 360 365 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 370 375 380 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 385 390 395 400 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 405 410 415 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 420 425 430 Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu 435 440 445 Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser 450 455 460 Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln 465 470 475 480 Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys 530 535 540 Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Ser Gly Ala Gly 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Gly Ser Gly Ser Gly 1190 1195 1200 Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu 1205 1210 1215 Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val 1220 1225 1230 Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala 1235 1240 1245 Val Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe 1250 1255 1260 Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu 1265 1270 1275 Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val 1280 1285 1290 Glu Gln Ala Arg Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val 1295 1300 1305 Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Lys 1310 1315 1320 Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val 1325 1330 1335 Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly 1340 1345 1350 Glu Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe 1355 1360 1365 Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn 1370 1375 1380 Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly 1385 1390 1395 Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala 1400 1405 1410 Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu 1415 1420 1425 <210> 38 <211> 1468 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (1458)..(1468) <223> optionally absent <400> 38 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr 35 40 45 Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser 50 55 60 Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn 65 70 75 80 Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys 85 90 95 Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala 100 105 110 Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr 115 120 125 Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn 130 135 140 Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu 145 150 155 160 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 165 170 175 Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln 180 185 190 Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu 195 200 205 Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser 210 215 220 Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser 225 230 235 240 Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg 245 250 255 Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp 260 265 270 Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr 275 280 285 Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile 290 295 300 Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 305 310 315 320 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 325 330 335 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 340 345 350 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 355 360 365 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 370 375 380 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 385 390 395 400 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 405 410 415 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 420 425 430 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 435 440 445 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 450 455 460 Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu 465 470 475 480 Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser 485 490 495 Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln 500 505 510 Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg 515 520 525 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 530 535 540 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 545 550 555 560 Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys 565 570 575 Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr 580 585 590 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 595 600 605 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 610 615 620 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 625 630 635 640 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 645 650 655 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 660 665 670 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 675 680 685 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Ser Gly Ala Gly 690 695 700 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 705 710 715 720 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 725 730 735 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 740 745 750 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 755 760 765 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 770 775 780 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 785 790 795 800 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 805 810 815 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 820 825 830 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 835 840 845 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 850 855 860 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 865 870 875 880 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 885 890 895 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 900 905 910 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 915 920 925 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 930 935 940 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 945 950 955 960 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 965 970 975 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 980 985 990 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 995 1000 1005 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu 1010 1015 1020 Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg 1025 1030 1035 Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu 1040 1045 1050 Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu 1055 1060 1065 Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His 1070 1075 1080 Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro 1085 1090 1095 Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val 1100 1105 1110 Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe 1115 1120 1125 Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly 1130 1135 1140 Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp 1145 1150 1155 Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys 1160 1165 1170 Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile 1175 1180 1185 Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp 1190 1195 1200 Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp 1205 1210 1215 Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Gly Ser Gly 1220 1225 1230 Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala 1235 1240 1245 Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys 1250 1255 1260 Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu 1265 1270 1275 Lys Ala Val Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile 1280 1285 1290 Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser 1295 1300 1305 Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr 1310 1315 1320 Ser Val Glu Gln Ala Arg Lys Ala Val Glu Ser Gly Ala Glu Phe 1325 1330 1335 Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys 1340 1345 1350 Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu 1355 1360 1365 Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe 1370 1375 1380 Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly 1385 1390 1395 Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu 1400 1405 1410 Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly 1415 1420 1425 Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu 1430 1435 1440 Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu Gly 1445 1450 1455 Gly Ser His His His His His His His His 1460 1465 <210> 39 <211> 1429 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 39 Glu Thr Gly Thr Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro 1 5 10 15 Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys 20 25 30 Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro 35 40 45 Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr 50 55 60 Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly 65 70 75 80 Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile 85 90 95 Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn 100 105 110 Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn 115 120 125 Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met 130 135 140 Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu 145 150 155 160 Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn 165 170 175 Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe 180 185 190 Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro 195 200 205 Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile 210 215 220 Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu 225 230 235 240 Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr 245 250 255 Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu 260 265 270 Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser 275 280 285 Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr 290 295 300 Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe 305 310 315 320 Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr 325 330 335 Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys 340 345 350 Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe 355 360 365 Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr 370 375 380 Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln 385 390 395 400 Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu 405 410 415 Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu 420 425 430 Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg 435 440 445 Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr 450 455 460 Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr 465 470 475 480 Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr 485 490 495 Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro 500 505 510 Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys 515 520 525 Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr 530 535 540 Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile 545 550 555 560 Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu 565 570 575 Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly 580 585 590 Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys 595 600 605 Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp 610 615 620 Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys 625 630 635 640 Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro 645 650 655 Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro 660 665 670 Ser Gly Ala Gly Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met 675 680 685 Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala 690 695 700 Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val 705 710 715 720 Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp 725 730 735 Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr 740 745 750 Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn 755 760 765 Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro 770 775 780 Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro 785 790 795 800 Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys 805 810 815 Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu 820 825 830 Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly 835 840 845 Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr 850 855 860 Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly 865 870 875 880 Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg 885 890 895 Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys 900 905 910 Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser 915 920 925 Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn 930 935 940 Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn 945 950 955 960 Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp 965 970 975 Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu 980 985 990 Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu 995 1000 1005 Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys 1010 1015 1020 Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr 1025 1030 1035 His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe 1040 1045 1050 Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr 1055 1060 1065 Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu 1070 1075 1080 Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg 1085 1090 1095 Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val 1100 1105 1110 Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val 1115 1120 1125 Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu 1130 1135 1140 Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly 1145 1150 1155 Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu 1160 1165 1170 Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu 1175 1180 1185 Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Gly 1190 1195 1200 Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala 1205 1210 1215 Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys 1220 1225 1230 His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala 1235 1240 1245 Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val His Leu Ile 1250 1255 1260 Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala 1265 1270 1275 Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr 1280 1285 1290 Val Thr Ser Val Glu Gln Ala Arg Lys Ala Val Glu Ser Gly Ala 1295 1300 1305 Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe 1310 1315 1320 Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro 1325 1330 1335 Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys 1340 1345 1350 Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met 1355 1360 1365 Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val 1370 1375 1380 Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala 1385 1390 1395 Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val 1400 1405 1410 Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr 1415 1420 1425 Glu <210> 40 <211> 1440 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1430)..(1440) <223> optionally absent <400> 40 Glu Thr Gly Thr Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro 1 5 10 15 Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys 20 25 30 Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro 35 40 45 Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr 50 55 60 Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly 65 70 75 80 Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile 85 90 95 Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn 100 105 110 Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn 115 120 125 Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met 130 135 140 Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu 145 150 155 160 Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn 165 170 175 Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe 180 185 190 Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro 195 200 205 Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile 210 215 220 Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu 225 230 235 240 Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr 245 250 255 Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu 260 265 270 Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser 275 280 285 Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr 290 295 300 Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe 305 310 315 320 Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr 325 330 335 Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys 340 345 350 Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe 355 360 365 Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr 370 375 380 Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln 385 390 395 400 Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu 405 410 415 Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu 420 425 430 Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg 435 440 445 Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr 450 455 460 Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr 465 470 475 480 Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr 485 490 495 Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro 500 505 510 Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys 515 520 525 Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr 530 535 540 Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile 545 550 555 560 Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu 565 570 575 Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly 580 585 590 Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys 595 600 605 Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp 610 615 620 Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys 625 630 635 640 Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro 645 650 655 Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro 660 665 670 Ser Gly Ala Gly Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met 675 680 685 Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala 690 695 700 Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val 705 710 715 720 Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp 725 730 735 Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr 740 745 750 Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn 755 760 765 Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro 770 775 780 Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro 785 790 795 800 Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys 805 810 815 Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu 820 825 830 Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly 835 840 845 Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr 850 855 860 Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly 865 870 875 880 Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg 885 890 895 Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys 900 905 910 Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser 915 920 925 Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn 930 935 940 Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn 945 950 955 960 Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp 965 970 975 Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu 980 985 990 Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu 995 1000 1005 Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys 1010 1015 1020 Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr 1025 1030 1035 His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe 1040 1045 1050 Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr 1055 1060 1065 Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu 1070 1075 1080 Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg 1085 1090 1095 Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val 1100 1105 1110 Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val 1115 1120 1125 Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu 1130 1135 1140 Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly 1145 1150 1155 Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu 1160 1165 1170 Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu 1175 1180 1185 Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Gly 1190 1195 1200 Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala 1205 1210 1215 Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys 1220 1225 1230 His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala 1235 1240 1245 Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val His Leu Ile 1250 1255 1260 Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala 1265 1270 1275 Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr 1280 1285 1290 Val Thr Ser Val Glu Gln Ala Arg Lys Ala Val Glu Ser Gly Ala 1295 1300 1305 Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe 1310 1315 1320 Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro 1325 1330 1335 Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys 1340 1345 1350 Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met 1355 1360 1365 Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val 1370 1375 1380 Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala 1385 1390 1395 Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val 1400 1405 1410 Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr 1415 1420 1425 Glu Gly Gly Ser His His His His His His His His 1430 1435 1440 <210> 41 <211> 1403 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1199)..(1199) <223> X is absent or is an amino acid linker <400> 41 Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr 1 5 10 15 Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser 20 25 30 Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn 35 40 45 Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys 50 55 60 Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala 65 70 75 80 Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr 85 90 95 Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn 100 105 110 Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln 145 150 155 160 Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu 165 170 175 Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser 180 185 190 Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser 195 200 205 Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg 210 215 220 Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp 225 230 235 240 Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr 245 250 255 Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile 260 265 270 Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 275 280 285 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 290 295 300 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 305 310 315 320 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 325 330 335 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 340 345 350 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 355 360 365 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 370 375 380 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 385 390 395 400 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 405 410 415 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 420 425 430 Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu 435 440 445 Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser 450 455 460 Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln 465 470 475 480 Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys 530 535 540 Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Ser Gly Ala Gly 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Xaa Lys Met Glu Glu 1190 1195 1200 Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn Ser 1205 1210 1215 Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly 1220 1225 1230 Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr 1235 1240 1245 Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile 1250 1255 1260 Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala Val 1265 1270 1275 Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu 1280 1285 1290 Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly 1295 1300 1305 Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His 1310 1315 1320 Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe 1325 1330 1335 Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro 1340 1345 1350 Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala 1355 1360 1365 Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr 1370 1375 1380 Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile 1385 1390 1395 Arg Gly Ala Thr Glu 1400 <210> 42 <211> 1446 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (1231)..(1231) <223> X is absent or is an amino acid linker <220> <221> MISC_FEATURE <222> (1436)..(1446) <223> optionally absent <400> 42 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr 35 40 45 Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser 50 55 60 Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn 65 70 75 80 Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys 85 90 95 Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala 100 105 110 Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr 115 120 125 Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn 130 135 140 Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu 145 150 155 160 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 165 170 175 Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln 180 185 190 Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu 195 200 205 Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser 210 215 220 Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser 225 230 235 240 Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg 245 250 255 Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp 260 265 270 Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr 275 280 285 Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile 290 295 300 Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 305 310 315 320 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 325 330 335 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 340 345 350 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 355 360 365 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 370 375 380 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 385 390 395 400 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 405 410 415 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 420 425 430 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 435 440 445 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 450 455 460 Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu 465 470 475 480 Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser 485 490 495 Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln 500 505 510 Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg 515 520 525 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 530 535 540 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 545 550 555 560 Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys 565 570 575 Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr 580 585 590 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 595 600 605 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 610 615 620 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 625 630 635 640 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 645 650 655 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 660 665 670 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 675 680 685 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Ser Gly Ala Gly 690 695 700 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 705 710 715 720 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 725 730 735 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 740 745 750 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 755 760 765 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 770 775 780 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 785 790 795 800 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 805 810 815 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 820 825 830 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 835 840 845 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 850 855 860 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 865 870 875 880 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 885 890 895 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 900 905 910 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 915 920 925 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 930 935 940 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 945 950 955 960 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 965 970 975 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 980 985 990 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 995 1000 1005 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu 1010 1015 1020 Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg 1025 1030 1035 Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu 1040 1045 1050 Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu 1055 1060 1065 Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His 1070 1075 1080 Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro 1085 1090 1095 Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val 1100 1105 1110 Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe 1115 1120 1125 Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly 1130 1135 1140 Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp 1145 1150 1155 Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys 1160 1165 1170 Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile 1175 1180 1185 Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp 1190 1195 1200 Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp 1205 1210 1215 Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Xaa Lys Met 1220 1225 1230 Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala 1235 1240 1245 Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala 1250 1255 1260 Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala 1265 1270 1275 Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala 1280 1285 1290 Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys 1295 1300 1305 Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp 1310 1315 1320 Glu Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met 1325 1330 1335 Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu 1340 1345 1350 Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro 1355 1360 1365 Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe 1370 1375 1380 Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe 1385 1390 1395 Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys 1400 1405 1410 Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu 1415 1420 1425 Lys Ile Arg Gly Ala Thr Glu Gly Gly Ser His His His His His 1430 1435 1440 His His His 1445 <210> 43 <211> 1406 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 43 Glu Thr Gly Thr Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro 1 5 10 15 Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys 20 25 30 Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro 35 40 45 Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr 50 55 60 Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly 65 70 75 80 Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile 85 90 95 Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn 100 105 110 Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn 115 120 125 Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met 130 135 140 Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu 145 150 155 160 Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn 165 170 175 Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe 180 185 190 Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro 195 200 205 Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile 210 215 220 Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu 225 230 235 240 Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr 245 250 255 Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu 260 265 270 Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser 275 280 285 Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr 290 295 300 Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe 305 310 315 320 Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr 325 330 335 Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys 340 345 350 Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe 355 360 365 Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr 370 375 380 Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln 385 390 395 400 Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu 405 410 415 Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu 420 425 430 Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg 435 440 445 Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr 450 455 460 Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr 465 470 475 480 Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr 485 490 495 Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro 500 505 510 Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys 515 520 525 Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr 530 535 540 Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile 545 550 555 560 Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu 565 570 575 Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly 580 585 590 Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys 595 600 605 Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp 610 615 620 Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys 625 630 635 640 Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro 645 650 655 Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro 660 665 670 Ser Gly Ala Gly Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met 675 680 685 Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala 690 695 700 Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val 705 710 715 720 Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp 725 730 735 Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr 740 745 750 Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn 755 760 765 Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro 770 775 780 Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro 785 790 795 800 Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys 805 810 815 Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu 820 825 830 Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly 835 840 845 Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr 850 855 860 Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly 865 870 875 880 Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg 885 890 895 Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys 900 905 910 Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser 915 920 925 Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn 930 935 940 Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn 945 950 955 960 Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp 965 970 975 Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu 980 985 990 Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu 995 1000 1005 Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys 1010 1015 1020 Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr 1025 1030 1035 His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe 1040 1045 1050 Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr 1055 1060 1065 Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu 1070 1075 1080 Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg 1085 1090 1095 Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val 1100 1105 1110 Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val 1115 1120 1125 Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu 1130 1135 1140 Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly 1145 1150 1155 Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu 1160 1165 1170 Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu 1175 1180 1185 Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Lys 1190 1195 1200 Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg 1205 1210 1215 Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe 1220 1225 1230 Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp 1235 1240 1245 Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly 1250 1255 1260 Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg 1265 1270 1275 Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu 1280 1285 1290 Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr 1295 1300 1305 Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys 1310 1315 1320 Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly 1325 1330 1335 Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys 1340 1345 1350 Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp 1355 1360 1365 Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val 1370 1375 1380 Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val 1385 1390 1395 Glu Lys Ile Arg Gly Ala Thr Glu 1400 1405 <210> 44 <211> 1417 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1407)..(1417) <223> optionally absent <400> 44 Glu Thr Gly Thr Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro 1 5 10 15 Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys 20 25 30 Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro 35 40 45 Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr 50 55 60 Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly 65 70 75 80 Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile 85 90 95 Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn 100 105 110 Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn 115 120 125 Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met 130 135 140 Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu 145 150 155 160 Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn 165 170 175 Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe 180 185 190 Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro 195 200 205 Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile 210 215 220 Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu 225 230 235 240 Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr 245 250 255 Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu 260 265 270 Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser 275 280 285 Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr 290 295 300 Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe 305 310 315 320 Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr 325 330 335 Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys 340 345 350 Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe 355 360 365 Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr 370 375 380 Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln 385 390 395 400 Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu 405 410 415 Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu 420 425 430 Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg 435 440 445 Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr 450 455 460 Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr 465 470 475 480 Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr 485 490 495 Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro 500 505 510 Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys 515 520 525 Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr 530 535 540 Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile 545 550 555 560 Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu 565 570 575 Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly 580 585 590 Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys 595 600 605 Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp 610 615 620 Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys 625 630 635 640 Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro 645 650 655 Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro 660 665 670 Ser Gly Ala Gly Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met 675 680 685 Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala 690 695 700 Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val 705 710 715 720 Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp 725 730 735 Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr 740 745 750 Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn 755 760 765 Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro 770 775 780 Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro 785 790 795 800 Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys 805 810 815 Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu 820 825 830 Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly 835 840 845 Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr 850 855 860 Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly 865 870 875 880 Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg 885 890 895 Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys 900 905 910 Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser 915 920 925 Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn 930 935 940 Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn 945 950 955 960 Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp 965 970 975 Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu 980 985 990 Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu 995 1000 1005 Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys 1010 1015 1020 Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr 1025 1030 1035 His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe 1040 1045 1050 Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr 1055 1060 1065 Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu 1070 1075 1080 Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg 1085 1090 1095 Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val 1100 1105 1110 Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val 1115 1120 1125 Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu 1130 1135 1140 Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly 1145 1150 1155 Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu 1160 1165 1170 Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu 1175 1180 1185 Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Lys 1190 1195 1200 Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg 1205 1210 1215 Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe 1220 1225 1230 Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp 1235 1240 1245 Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly 1250 1255 1260 Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg 1265 1270 1275 Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu 1280 1285 1290 Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr 1295 1300 1305 Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys 1310 1315 1320 Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly 1325 1330 1335 Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys 1340 1345 1350 Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp 1355 1360 1365 Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val 1370 1375 1380 Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val 1385 1390 1395 Glu Lys Ile Arg Gly Ala Thr Glu Gly Gly Ser His His His His 1400 1405 1410 His His His His 1415 <210> 45 <211> 426 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 45 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 1 5 10 15 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 20 25 30 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 35 40 45 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 50 55 60 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 65 70 75 80 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 85 90 95 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 100 105 110 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 115 120 125 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 130 135 140 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 145 150 155 160 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 165 170 175 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 180 185 190 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Gly Gly Ser Gly 195 200 205 Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu Ala Ala Arg Met 210 215 220 Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala Val Leu Arg Ala Asn 225 230 235 240 Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe Leu Gly Gly 245 250 255 Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val 260 265 270 Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile Ile Gly Ala 275 280 285 Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val Glu Ser Gly 290 295 300 Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe 305 310 315 320 Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr 325 330 335 Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe 340 345 350 Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala Met Lys Gly Pro 355 360 365 Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn 370 375 380 Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly Val Gly Glu 385 390 395 400 Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys Ala Lys Ala 405 410 415 Phe Val Glu Lys Ile Glu Gly Ala Thr Glu 420 425 <210> 46 <211> 469 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (459)..(469) <223> optionally absent <400> 46 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 35 40 45 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 50 55 60 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 65 70 75 80 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 85 90 95 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 100 105 110 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 115 120 125 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 130 135 140 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 145 150 155 160 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 165 170 175 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 180 185 190 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 195 200 205 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 210 215 220 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Gly Gly Ser Gly 225 230 235 240 Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu Ala Ala Arg Met 245 250 255 Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala Val Leu Arg Ala Asn 260 265 270 Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe Leu Gly Gly 275 280 285 Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val 290 295 300 Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile Ile Gly Ala 305 310 315 320 Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val Glu Ser Gly 325 330 335 Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe 340 345 350 Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr 355 360 365 Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe 370 375 380 Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala Met Lys Gly Pro 385 390 395 400 Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn 405 410 415 Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly Val Gly Glu 420 425 430 Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys Ala Lys Ala 435 440 445 Phe Val Glu Lys Ile Glu Gly Ala Thr Glu Gly Gly Ser His His His 450 455 460 His His His His His 465 <210> 47 <211> 430 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 47 Glu Thr Gly Thr Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 1 5 10 15 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 20 25 30 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 35 40 45 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 50 55 60 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 65 70 75 80 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala 85 90 95 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 100 105 110 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 115 120 125 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 130 135 140 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 145 150 155 160 Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 165 170 175 Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 180 185 190 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 195 200 205 Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu 210 215 220 Ala Ala Arg Met Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala Val 225 230 235 240 Leu Arg Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val 245 250 255 Phe Leu Gly Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp 260 265 270 Ala Asp Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala 275 280 285 Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala 290 295 300 Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu 305 310 315 320 Ile Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val 325 330 335 Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile 340 345 350 Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala 355 360 365 Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val 370 375 380 Asn Leu Asp Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val 385 390 395 400 Gly Val Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu 405 410 415 Lys Ala Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu 420 425 430 <210> 48 <211> 441 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (431)..(441) <223> optionally absent <400> 48 Glu Thr Gly Thr Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 1 5 10 15 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 20 25 30 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 35 40 45 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 50 55 60 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 65 70 75 80 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala 85 90 95 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 100 105 110 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 115 120 125 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 130 135 140 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 145 150 155 160 Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 165 170 175 Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 180 185 190 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 195 200 205 Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu 210 215 220 Ala Ala Arg Met Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala Val 225 230 235 240 Leu Arg Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val 245 250 255 Phe Leu Gly Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp 260 265 270 Ala Asp Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala 275 280 285 Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala 290 295 300 Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu 305 310 315 320 Ile Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val 325 330 335 Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile 340 345 350 Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala 355 360 365 Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val 370 375 380 Asn Leu Asp Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val 385 390 395 400 Gly Val Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu 405 410 415 Lys Ala Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu Gly Gly 420 425 430 Ser His His His His His His His His 435 440 <210> 49 <211> 408 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (205)..(205) <223> X is absent or is an amino acid linker <400> 49 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 1 5 10 15 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 20 25 30 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 35 40 45 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 50 55 60 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 65 70 75 80 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 85 90 95 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 100 105 110 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 115 120 125 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 130 135 140 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 145 150 155 160 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 165 170 175 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 180 185 190 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Xaa Met Glu Glu 195 200 205 Leu Phe Lys Glu His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val 210 215 220 Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe Leu Gly Gly Val Asp 225 230 235 240 Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys 245 250 255 Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile Ile Gly Ala Gly Thr 260 265 270 Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val Glu Ser Gly Ala Glu 275 280 285 Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys 290 295 300 Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu 305 310 315 320 Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly 325 330 335 Glu Val Val Gly Pro Gln Phe Val Glu Ala Met Lys Gly Pro Phe Pro 340 345 350 Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala 355 360 365 Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly Val Gly Glu Ala Leu 370 375 380 Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys Ala Lys Ala Phe Val 385 390 395 400 Glu Lys Ile Glu Gly Ala Thr Glu 405 <210> 50 <211> 451 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (237)..(237) <223> X is absent or is an amino acid linker <220> <221> MISC_FEATURE <222> (441)..(451) <223> optionally absent <400> 50 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 35 40 45 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 50 55 60 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 65 70 75 80 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 85 90 95 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 100 105 110 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 115 120 125 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 130 135 140 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 145 150 155 160 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 165 170 175 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 180 185 190 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 195 200 205 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 210 215 220 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Xaa Met Glu Glu 225 230 235 240 Leu Phe Lys Glu His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val 245 250 255 Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe Leu Gly Gly Val Asp 260 265 270 Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys 275 280 285 Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile Ile Gly Ala Gly Thr 290 295 300 Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val Glu Ser Gly Ala Glu 305 310 315 320 Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys 325 330 335 Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu 340 345 350 Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly 355 360 365 Glu Val Val Gly Pro Gln Phe Val Glu Ala Met Lys Gly Pro Phe Pro 370 375 380 Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala 385 390 395 400 Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly Val Gly Glu Ala Leu 405 410 415 Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys Ala Lys Ala Phe Val 420 425 430 Glu Lys Ile Glu Gly Ala Thr Glu Gly Gly Ser His His His His His 435 440 445 His His His 450 <210> 51 <211> 412 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (209)..(209) <223> X is absent or is an amino acid linker <400> 51 Glu Thr Gly Thr Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 1 5 10 15 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 20 25 30 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 35 40 45 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 50 55 60 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 65 70 75 80 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala 85 90 95 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 100 105 110 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 115 120 125 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 130 135 140 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 145 150 155 160 Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 165 170 175 Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 180 185 190 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 195 200 205 Xaa Met Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala Val Leu Arg 210 215 220 Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe Leu 225 230 235 240 Gly Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp 245 250 255 Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile Ile 260 265 270 Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val Glu 275 280 285 Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser 290 295 300 Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met Thr 305 310 315 320 Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys 325 330 335 Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala Met Lys 340 345 350 Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu 355 360 365 Asp Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly Val 370 375 380 Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys Ala 385 390 395 400 Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu 405 410 <210> 52 <211> 423 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (209)..(209) <223> X is absent or is an amino acid linker <220> <221> MISC_FEATURE <222> (413)..(423) <223> optionally absent <400> 52 Glu Thr Gly Thr Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 1 5 10 15 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 20 25 30 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 35 40 45 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 50 55 60 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 65 70 75 80 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala 85 90 95 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 100 105 110 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 115 120 125 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 130 135 140 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 145 150 155 160 Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 165 170 175 Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 180 185 190 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 195 200 205 Xaa Met Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala Val Leu Arg 210 215 220 Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe Leu 225 230 235 240 Gly Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp 245 250 255 Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile Ile 260 265 270 Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val Glu 275 280 285 Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser 290 295 300 Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met Thr 305 310 315 320 Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys 325 330 335 Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala Met Lys 340 345 350 Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu 355 360 365 Asp Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly Val 370 375 380 Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys Ala 385 390 395 400 Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu Gly Gly Ser His 405 410 415 His His His His His His His 420 <210> 53 <211> 430 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 53 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 1 5 10 15 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 20 25 30 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 35 40 45 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 50 55 60 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 65 70 75 80 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 85 90 95 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 100 105 110 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 115 120 125 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 130 135 140 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 145 150 155 160 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 165 170 175 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 180 185 190 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Gly Ser Gly Ser 195 200 205 Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu 210 215 220 Ala Ala Arg Met Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala Val 225 230 235 240 Leu Arg Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val 245 250 255 Phe Leu Gly Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp 260 265 270 Ala Asp Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala 275 280 285 Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala 290 295 300 Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu 305 310 315 320 Ile Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val 325 330 335 Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile 340 345 350 Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala 355 360 365 Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val 370 375 380 Asn Leu Asp Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val 385 390 395 400 Gly Val Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu 405 410 415 Lys Ala Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu 420 425 430 <210> 54 <211> 473 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (463)..(473) <223> optionally absent <400> 54 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 35 40 45 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 50 55 60 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 65 70 75 80 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 85 90 95 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 100 105 110 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 115 120 125 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 130 135 140 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 145 150 155 160 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 165 170 175 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 180 185 190 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 195 200 205 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 210 215 220 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Gly Ser Gly Ser 225 230 235 240 Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu 245 250 255 Ala Ala Arg Met Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala Val 260 265 270 Leu Arg Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val 275 280 285 Phe Leu Gly Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp 290 295 300 Ala Asp Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala 305 310 315 320 Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala 325 330 335 Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu 340 345 350 Ile Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val 355 360 365 Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile 370 375 380 Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala 385 390 395 400 Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val 405 410 415 Asn Leu Asp Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val 420 425 430 Gly Val Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu 435 440 445 Lys Ala Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu Gly Gly 450 455 460 Ser His His His His His His His His 465 470 <210> 55 <211> 434 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 55 Glu Thr Gly Thr Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 1 5 10 15 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 20 25 30 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 35 40 45 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 50 55 60 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 65 70 75 80 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala 85 90 95 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 100 105 110 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 115 120 125 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 130 135 140 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 145 150 155 160 Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 165 170 175 Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 180 185 190 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 195 200 205 Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala 210 215 220 Lys Ala Glu Glu Ala Ala Arg Met Glu Glu Leu Phe Lys Glu His Lys 225 230 235 240 Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Lys Lys Lys 245 250 255 Ala Leu Ala Val Phe Leu Gly Gly Val Asp Leu Ile Glu Ile Thr Phe 260 265 270 Thr Val Pro Asp Ala Asp Thr Val Ile Lys Glu Leu Ser Phe Leu Lys 275 280 285 Glu Met Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln 290 295 300 Ala Arg Glu Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His 305 310 315 320 Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr 325 330 335 Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu 340 345 350 Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln 355 360 365 Phe Val Glu Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro 370 375 380 Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Glu Ala Gly 385 390 395 400 Val Gln Ala Val Gly Val Gly Glu Ala Leu Asn Glu Gly Thr Pro Val 405 410 415 Glu Val Ala Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Glu Gly Ala 420 425 430 Thr Glu <210> 56 <211> 445 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (435)..(445) <223> optionally absent <400> 56 Glu Thr Gly Thr Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 1 5 10 15 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 20 25 30 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 35 40 45 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 50 55 60 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 65 70 75 80 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala 85 90 95 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 100 105 110 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 115 120 125 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 130 135 140 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 145 150 155 160 Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 165 170 175 Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 180 185 190 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 195 200 205 Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala 210 215 220 Lys Ala Glu Glu Ala Ala Arg Met Glu Glu Leu Phe Lys Glu His Lys 225 230 235 240 Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Lys Lys Lys 245 250 255 Ala Leu Ala Val Phe Leu Gly Gly Val Asp Leu Ile Glu Ile Thr Phe 260 265 270 Thr Val Pro Asp Ala Asp Thr Val Ile Lys Glu Leu Ser Phe Leu Lys 275 280 285 Glu Met Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln 290 295 300 Ala Arg Glu Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His 305 310 315 320 Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr 325 330 335 Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu 340 345 350 Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln 355 360 365 Phe Val Glu Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro 370 375 380 Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Glu Ala Gly 385 390 395 400 Val Gln Ala Val Gly Val Gly Glu Ala Leu Asn Glu Gly Thr Pro Val 405 410 415 Glu Val Ala Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Glu Gly Ala 420 425 430 Thr Glu Gly Gly Ser His His His His His His His His 435 440 445 <210> 57 <211> 408 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (205)..(205) <223> X is absent or is an amino acid linker <400> 57 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 1 5 10 15 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 20 25 30 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 35 40 45 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 50 55 60 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 65 70 75 80 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 85 90 95 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 100 105 110 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 115 120 125 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 130 135 140 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 145 150 155 160 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 165 170 175 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 180 185 190 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Xaa Met Glu Glu 195 200 205 Leu Phe Lys Glu His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val 210 215 220 Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe Leu Gly Gly Val Asp 225 230 235 240 Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys 245 250 255 Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile Ile Gly Ala Gly Thr 260 265 270 Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val Glu Ser Gly Ala Glu 275 280 285 Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys 290 295 300 Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu 305 310 315 320 Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly 325 330 335 Glu Val Val Gly Pro Gln Phe Val Glu Ala Met Lys Gly Pro Phe Pro 340 345 350 Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala 355 360 365 Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly Val Gly Glu Ala Leu 370 375 380 Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys Ala Lys Ala Phe Val 385 390 395 400 Glu Lys Ile Glu Gly Ala Thr Glu 405 <210> 58 <211> 451 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (237)..(237) <223> X is absent or is an amino acid linker <220> <221> MISC_FEATURE <222> (441)..(451) <223> optionally absent <400> 58 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 35 40 45 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 50 55 60 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 65 70 75 80 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 85 90 95 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 100 105 110 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 115 120 125 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 130 135 140 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 145 150 155 160 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 165 170 175 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 180 185 190 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 195 200 205 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 210 215 220 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Xaa Met Glu Glu 225 230 235 240 Leu Phe Lys Glu His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val 245 250 255 Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe Leu Gly Gly Val Asp 260 265 270 Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys 275 280 285 Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile Ile Gly Ala Gly Thr 290 295 300 Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val Glu Ser Gly Ala Glu 305 310 315 320 Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys 325 330 335 Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu 340 345 350 Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly 355 360 365 Glu Val Val Gly Pro Gln Phe Val Glu Ala Met Lys Gly Pro Phe Pro 370 375 380 Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala 385 390 395 400 Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly Val Gly Glu Ala Leu 405 410 415 Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys Ala Lys Ala Phe Val 420 425 430 Glu Lys Ile Glu Gly Ala Thr Glu Gly Gly Ser His His His His His 435 440 445 His His His 450 <210> 59 <211> 412 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (209)..(209) <223> X is absent or is an amino acid linker <400> 59 Glu Thr Gly Thr Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 1 5 10 15 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 20 25 30 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 35 40 45 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 50 55 60 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 65 70 75 80 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala 85 90 95 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 100 105 110 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 115 120 125 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 130 135 140 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 145 150 155 160 Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 165 170 175 Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 180 185 190 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 195 200 205 Xaa Met Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala Val Leu Arg 210 215 220 Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe Leu 225 230 235 240 Gly Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp 245 250 255 Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile Ile 260 265 270 Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val Glu 275 280 285 Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser 290 295 300 Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met Thr 305 310 315 320 Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys 325 330 335 Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala Met Lys 340 345 350 Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu 355 360 365 Asp Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly Val 370 375 380 Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys Ala 385 390 395 400 Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu 405 410 <210> 60 <211> 423 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (209)..(209) <223> X is absent or is an amino acid linker <220> <221> MISC_FEATURE <222> (413)..(423) <223> optionally absent <400> 60 Glu Thr Gly Thr Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 1 5 10 15 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 20 25 30 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 35 40 45 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 50 55 60 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 65 70 75 80 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala 85 90 95 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 100 105 110 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 115 120 125 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 130 135 140 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 145 150 155 160 Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 165 170 175 Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 180 185 190 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 195 200 205 Xaa Met Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala Val Leu Arg 210 215 220 Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe Leu 225 230 235 240 Gly Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp 245 250 255 Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile Ile 260 265 270 Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val Glu 275 280 285 Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser 290 295 300 Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met Thr 305 310 315 320 Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys 325 330 335 Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala Met Lys 340 345 350 Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu 355 360 365 Asp Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly Val 370 375 380 Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys Ala 385 390 395 400 Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu Gly Gly Ser His 405 410 415 His His His His His His His 420 <210> 61 <211> 434 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 61 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 1 5 10 15 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 20 25 30 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 35 40 45 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 50 55 60 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 65 70 75 80 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 85 90 95 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 100 105 110 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 115 120 125 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 130 135 140 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 145 150 155 160 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 165 170 175 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 180 185 190 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Gly Gly Ser Gly 195 200 205 Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala 210 215 220 Lys Ala Glu Glu Ala Ala Arg Met Glu Glu Leu Phe Lys Glu His Lys 225 230 235 240 Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Lys Lys Lys 245 250 255 Ala Leu Ala Val Phe Leu Gly Gly Val Asp Leu Ile Glu Ile Thr Phe 260 265 270 Thr Val Pro Asp Ala Asp Thr Val Ile Lys Glu Leu Ser Phe Leu Lys 275 280 285 Glu Met Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln 290 295 300 Ala Arg Glu Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His 305 310 315 320 Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr 325 330 335 Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu 340 345 350 Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln 355 360 365 Phe Val Glu Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro 370 375 380 Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Glu Ala Gly 385 390 395 400 Val Gln Ala Val Gly Val Gly Glu Ala Leu Asn Glu Gly Thr Pro Val 405 410 415 Glu Val Ala Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Glu Gly Ala 420 425 430 Thr Glu <210> 62 <211> 477 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (467)..(477) <223> optionally absent <400> 62 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 35 40 45 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 50 55 60 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 65 70 75 80 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 85 90 95 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 100 105 110 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 115 120 125 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 130 135 140 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 145 150 155 160 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 165 170 175 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 180 185 190 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 195 200 205 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 210 215 220 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Gly Gly Ser Gly 225 230 235 240 Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala 245 250 255 Lys Ala Glu Glu Ala Ala Arg Met Glu Glu Leu Phe Lys Glu His Lys 260 265 270 Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Lys Lys Lys 275 280 285 Ala Leu Ala Val Phe Leu Gly Gly Val Asp Leu Ile Glu Ile Thr Phe 290 295 300 Thr Val Pro Asp Ala Asp Thr Val Ile Lys Glu Leu Ser Phe Leu Lys 305 310 315 320 Glu Met Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln 325 330 335 Ala Arg Glu Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His 340 345 350 Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr 355 360 365 Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu 370 375 380 Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln 385 390 395 400 Phe Val Glu Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro 405 410 415 Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Glu Ala Gly 420 425 430 Val Gln Ala Val Gly Val Gly Glu Ala Leu Asn Glu Gly Thr Pro Val 435 440 445 Glu Val Ala Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Glu Gly Ala 450 455 460 Thr Glu Gly Gly Ser His His His His His His His His 465 470 475 <210> 63 <211> 438 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 63 Glu Thr Gly Thr Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 1 5 10 15 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 20 25 30 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 35 40 45 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 50 55 60 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 65 70 75 80 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala 85 90 95 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 100 105 110 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 115 120 125 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 130 135 140 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 145 150 155 160 Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 165 170 175 Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 180 185 190 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 195 200 205 Gly Gly Ser Gly Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser 210 215 220 Glu Lys Ala Ala Lys Ala Glu Glu Ala Ala Arg Met Glu Glu Leu Phe 225 230 235 240 Lys Glu His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu 245 250 255 Ala Lys Lys Lys Ala Leu Ala Val Phe Leu Gly Gly Val Asp Leu Ile 260 265 270 Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Glu Leu 275 280 285 Ser Phe Leu Lys Glu Met Gly Ala Ile Ile Gly Ala Gly Thr Val Thr 290 295 300 Ser Val Glu Gln Ala Arg Glu Ala Val Glu Ser Gly Ala Glu Phe Ile 305 310 315 320 Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Glu 325 330 335 Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys 340 345 350 Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val 355 360 365 Val Gly Pro Gln Phe Val Glu Ala Met Lys Gly Pro Phe Pro Asn Val 370 375 380 Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp 385 390 395 400 Phe Glu Ala Gly Val Gln Ala Val Gly Val Gly Glu Ala Leu Asn Glu 405 410 415 Gly Thr Pro Val Glu Val Ala Glu Lys Ala Lys Ala Phe Val Glu Lys 420 425 430 Ile Glu Gly Ala Thr Glu 435 <210> 64 <211> 449 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (439)..(449) <223> optionally absent <400> 64 Glu Thr Gly Thr Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 1 5 10 15 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 20 25 30 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 35 40 45 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 50 55 60 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 65 70 75 80 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala 85 90 95 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 100 105 110 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 115 120 125 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 130 135 140 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 145 150 155 160 Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 165 170 175 Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 180 185 190 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 195 200 205 Gly Gly Ser Gly Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser 210 215 220 Glu Lys Ala Ala Lys Ala Glu Glu Ala Ala Arg Met Glu Glu Leu Phe 225 230 235 240 Lys Glu His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu 245 250 255 Ala Lys Lys Lys Ala Leu Ala Val Phe Leu Gly Gly Val Asp Leu Ile 260 265 270 Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Glu Leu 275 280 285 Ser Phe Leu Lys Glu Met Gly Ala Ile Ile Gly Ala Gly Thr Val Thr 290 295 300 Ser Val Glu Gln Ala Arg Glu Ala Val Glu Ser Gly Ala Glu Phe Ile 305 310 315 320 Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Glu 325 330 335 Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys 340 345 350 Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val 355 360 365 Val Gly Pro Gln Phe Val Glu Ala Met Lys Gly Pro Phe Pro Asn Val 370 375 380 Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp 385 390 395 400 Phe Glu Ala Gly Val Gln Ala Val Gly Val Gly Glu Ala Leu Asn Glu 405 410 415 Gly Thr Pro Val Glu Val Ala Glu Lys Ala Lys Ala Phe Val Glu Lys 420 425 430 Ile Glu Gly Ala Thr Glu Gly Gly Ser His His His His His His His 435 440 445 His <210> 65 <211> 408 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (205)..(205) <223> X is absent or is an amino acid linker <400> 65 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 1 5 10 15 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 20 25 30 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 35 40 45 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 50 55 60 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 65 70 75 80 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 85 90 95 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 100 105 110 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 115 120 125 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 130 135 140 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 145 150 155 160 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 165 170 175 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 180 185 190 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Xaa Met Glu Glu 195 200 205 Leu Phe Lys Glu His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val 210 215 220 Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe Leu Gly Gly Val Asp 225 230 235 240 Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys 245 250 255 Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile Ile Gly Ala Gly Thr 260 265 270 Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val Glu Ser Gly Ala Glu 275 280 285 Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys 290 295 300 Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu 305 310 315 320 Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly 325 330 335 Glu Val Val Gly Pro Gln Phe Val Glu Ala Met Lys Gly Pro Phe Pro 340 345 350 Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala 355 360 365 Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly Val Gly Glu Ala Leu 370 375 380 Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys Ala Lys Ala Phe Val 385 390 395 400 Glu Lys Ile Glu Gly Ala Thr Glu 405 <210> 66 <211> 451 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (237)..(237) <223> X is absent or is an amino acid linker <220> <221> MISC_FEATURE <222> (441)..(451) <223> optionally absent <400> 66 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 35 40 45 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 50 55 60 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 65 70 75 80 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 85 90 95 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 100 105 110 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 115 120 125 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 130 135 140 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 145 150 155 160 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 165 170 175 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 180 185 190 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 195 200 205 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 210 215 220 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Xaa Met Glu Glu 225 230 235 240 Leu Phe Lys Glu His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val 245 250 255 Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe Leu Gly Gly Val Asp 260 265 270 Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys 275 280 285 Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile Ile Gly Ala Gly Thr 290 295 300 Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val Glu Ser Gly Ala Glu 305 310 315 320 Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys 325 330 335 Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu 340 345 350 Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly 355 360 365 Glu Val Val Gly Pro Gln Phe Val Glu Ala Met Lys Gly Pro Phe Pro 370 375 380 Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala 385 390 395 400 Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly Val Gly Glu Ala Leu 405 410 415 Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys Ala Lys Ala Phe Val 420 425 430 Glu Lys Ile Glu Gly Ala Thr Glu Gly Gly Ser His His His His His 435 440 445 His His His 450 <210> 67 <211> 412 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (209)..(209) <223> X is absent or is an amino acid linker <400> 67 Glu Thr Gly Thr Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 1 5 10 15 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 20 25 30 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 35 40 45 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 50 55 60 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 65 70 75 80 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala 85 90 95 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 100 105 110 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 115 120 125 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 130 135 140 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 145 150 155 160 Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 165 170 175 Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 180 185 190 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 195 200 205 Xaa Met Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala Val Leu Arg 210 215 220 Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe Leu 225 230 235 240 Gly Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp 245 250 255 Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile Ile 260 265 270 Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val Glu 275 280 285 Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser 290 295 300 Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met Thr 305 310 315 320 Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys 325 330 335 Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala Met Lys 340 345 350 Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu 355 360 365 Asp Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly Val 370 375 380 Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys Ala 385 390 395 400 Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu 405 410 <210> 68 <211> 423 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (209)..(209) <223> X is absent or is an amino acid linker <220> <221> MISC_FEATURE <222> (413)..(423) <223> optionally absent <400> 68 Glu Thr Gly Thr Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 1 5 10 15 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 20 25 30 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 35 40 45 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 50 55 60 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 65 70 75 80 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala 85 90 95 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 100 105 110 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 115 120 125 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 130 135 140 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 145 150 155 160 Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 165 170 175 Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 180 185 190 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 195 200 205 Xaa Met Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala Val Leu Arg 210 215 220 Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe Leu 225 230 235 240 Gly Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp 245 250 255 Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile Ile 260 265 270 Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val Glu 275 280 285 Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser 290 295 300 Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met Thr 305 310 315 320 Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys 325 330 335 Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala Met Lys 340 345 350 Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu 355 360 365 Asp Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly Val 370 375 380 Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys Ala 385 390 395 400 Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu Gly Gly Ser His 405 410 415 His His His His His His His 420 <210> 69 <211> 1467 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 69 Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr 1 5 10 15 Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser 20 25 30 Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn 35 40 45 Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys 50 55 60 Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala 65 70 75 80 Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr 85 90 95 Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn 100 105 110 Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln 145 150 155 160 Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu 165 170 175 Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser 180 185 190 Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser 195 200 205 Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg 210 215 220 Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp 225 230 235 240 Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr 245 250 255 Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile 260 265 270 Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 275 280 285 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 290 295 300 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 305 310 315 320 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 325 330 335 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 340 345 350 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 355 360 365 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 370 375 380 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 385 390 395 400 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 405 410 415 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 420 425 430 Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu 435 440 445 Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser 450 455 460 Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln 465 470 475 480 Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys 530 535 540 Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Ser Gly Ala Gly 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Gly Ser Gly Arg Glu 1190 1195 1200 Asn Leu Tyr Phe Gln Gly Gly Gly Gly Ser Gly Tyr Ile Pro Glu 1205 1210 1215 Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp 1220 1225 1230 Val Leu Leu Ser Thr Phe Leu Gly Gly Ser Gly Ser Gly Gly Ser 1235 1240 1245 Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu Ala Ala 1250 1255 1260 Arg Met Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala Val Leu 1265 1270 1275 Arg Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val 1280 1285 1290 Phe Leu Gly Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro 1295 1300 1305 Asp Ala Asp Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met 1310 1315 1320 Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala 1325 1330 1335 Arg Glu Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His 1340 1345 1350 Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Glu Gly Val Phe 1355 1360 1365 Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met 1370 1375 1380 Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val 1385 1390 1395 Gly Pro Gln Phe Val Glu Ala Met Lys Gly Pro Phe Pro Asn Val 1400 1405 1410 Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu 1415 1420 1425 Trp Phe Glu Ala Gly Val Gln Ala Val Gly Val Gly Glu Ala Leu 1430 1435 1440 Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys Ala Lys Ala Phe 1445 1450 1455 Val Glu Lys Ile Glu Gly Ala Thr Glu 1460 1465 <210> 70 <211> 1510 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (1500)..(1510) <223> optionally absent <400> 70 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr 35 40 45 Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser 50 55 60 Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn 65 70 75 80 Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys 85 90 95 Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala 100 105 110 Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr 115 120 125 Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn 130 135 140 Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu 145 150 155 160 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 165 170 175 Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln 180 185 190 Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu 195 200 205 Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser 210 215 220 Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser 225 230 235 240 Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg 245 250 255 Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp 260 265 270 Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr 275 280 285 Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile 290 295 300 Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 305 310 315 320 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 325 330 335 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 340 345 350 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 355 360 365 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 370 375 380 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 385 390 395 400 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 405 410 415 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 420 425 430 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 435 440 445 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 450 455 460 Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu 465 470 475 480 Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser 485 490 495 Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln 500 505 510 Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg 515 520 525 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 530 535 540 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 545 550 555 560 Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys 565 570 575 Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr 580 585 590 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 595 600 605 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 610 615 620 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 625 630 635 640 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 645 650 655 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 660 665 670 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 675 680 685 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Ser Gly Ala Gly 690 695 700 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 705 710 715 720 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 725 730 735 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 740 745 750 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 755 760 765 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 770 775 780 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 785 790 795 800 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 805 810 815 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 820 825 830 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 835 840 845 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 850 855 860 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 865 870 875 880 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 885 890 895 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 900 905 910 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 915 920 925 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 930 935 940 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 945 950 955 960 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 965 970 975 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 980 985 990 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 995 1000 1005 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu 1010 1015 1020 Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg 1025 1030 1035 Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu 1040 1045 1050 Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu 1055 1060 1065 Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His 1070 1075 1080 Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro 1085 1090 1095 Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val 1100 1105 1110 Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe 1115 1120 1125 Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly 1130 1135 1140 Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp 1145 1150 1155 Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys 1160 1165 1170 Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile 1175 1180 1185 Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp 1190 1195 1200 Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp 1205 1210 1215 Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Gly Ser Gly 1220 1225 1230 Arg Glu Asn Leu Tyr Phe Gln Gly Gly Gly Gly Ser Gly Tyr Ile 1235 1240 1245 Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly 1250 1255 1260 Glu Trp Val Leu Leu Ser Thr Phe Leu Gly Gly Ser Gly Ser Gly 1265 1270 1275 Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu 1280 1285 1290 Ala Ala Arg Met Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala 1295 1300 1305 Val Leu Arg Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala Leu 1310 1315 1320 Ala Val Phe Leu Gly Gly Val Asp Leu Ile Glu Ile Thr Phe Thr 1325 1330 1335 Val Pro Asp Ala Asp Thr Val Ile Lys Glu Leu Ser Phe Leu Lys 1340 1345 1350 Glu Met Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu 1355 1360 1365 Gln Ala Arg Glu Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser 1370 1375 1380 Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Glu Gly 1385 1390 1395 Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys 1400 1405 1410 Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu 1415 1420 1425 Val Val Gly Pro Gln Phe Val Glu Ala Met Lys Gly Pro Phe Pro 1430 1435 1440 Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val 1445 1450 1455 Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly Val Gly Glu 1460 1465 1470 Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys Ala Lys 1475 1480 1485 Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu Gly Gly Ser His 1490 1495 1500 His His His His His His His 1505 1510 <210> 71 <211> 1471 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 71 Glu Thr Gly Thr Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro 1 5 10 15 Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys 20 25 30 Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro 35 40 45 Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr 50 55 60 Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly 65 70 75 80 Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile 85 90 95 Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn 100 105 110 Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn 115 120 125 Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met 130 135 140 Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu 145 150 155 160 Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn 165 170 175 Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe 180 185 190 Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro 195 200 205 Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile 210 215 220 Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu 225 230 235 240 Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr 245 250 255 Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu 260 265 270 Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser 275 280 285 Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr 290 295 300 Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe 305 310 315 320 Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr 325 330 335 Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys 340 345 350 Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe 355 360 365 Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr 370 375 380 Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln 385 390 395 400 Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu 405 410 415 Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu 420 425 430 Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg 435 440 445 Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr 450 455 460 Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr 465 470 475 480 Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr 485 490 495 Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro 500 505 510 Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys 515 520 525 Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr 530 535 540 Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile 545 550 555 560 Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu 565 570 575 Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly 580 585 590 Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys 595 600 605 Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp 610 615 620 Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys 625 630 635 640 Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro 645 650 655 Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro 660 665 670 Ser Gly Ala Gly Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met 675 680 685 Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala 690 695 700 Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val 705 710 715 720 Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp 725 730 735 Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr 740 745 750 Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn 755 760 765 Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro 770 775 780 Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro 785 790 795 800 Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys 805 810 815 Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu 820 825 830 Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly 835 840 845 Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr 850 855 860 Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly 865 870 875 880 Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg 885 890 895 Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys 900 905 910 Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser 915 920 925 Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn 930 935 940 Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn 945 950 955 960 Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp 965 970 975 Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu 980 985 990 Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu 995 1000 1005 Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys 1010 1015 1020 Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr 1025 1030 1035 His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe 1040 1045 1050 Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr 1055 1060 1065 Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu 1070 1075 1080 Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg 1085 1090 1095 Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val 1100 1105 1110 Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val 1115 1120 1125 Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu 1130 1135 1140 Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly 1145 1150 1155 Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu 1160 1165 1170 Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu 1175 1180 1185 Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Gly 1190 1195 1200 Ser Gly Arg Glu Asn Leu Tyr Phe Gln Gly Gly Gly Gly Ser Gly 1205 1210 1215 Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys 1220 1225 1230 Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu Gly Gly Ser Gly 1235 1240 1245 Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala 1250 1255 1260 Glu Glu Ala Ala Arg Met Glu Glu Leu Phe Lys Glu His Lys Ile 1265 1270 1275 Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Lys Lys Lys 1280 1285 1290 Ala Leu Ala Val Phe Leu Gly Gly Val Asp Leu Ile Glu Ile Thr 1295 1300 1305 Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Glu Leu Ser Phe 1310 1315 1320 Leu Lys Glu Met Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser 1325 1330 1335 Val Glu Gln Ala Arg Glu Ala Val Glu Ser Gly Ala Glu Phe Ile 1340 1345 1350 Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu 1355 1360 1365 Glu Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu 1370 1375 1380 Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro 1385 1390 1395 Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala Met Lys Gly Pro 1400 1405 1410 Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp 1415 1420 1425 Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly Val 1430 1435 1440 Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys 1445 1450 1455 Ala Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu 1460 1465 1470 <210> 72 <211> 1482 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1472)..(1482) <223> optionally absent <400> 72 Glu Thr Gly Thr Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro 1 5 10 15 Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys 20 25 30 Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro 35 40 45 Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr 50 55 60 Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly 65 70 75 80 Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile 85 90 95 Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn 100 105 110 Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn 115 120 125 Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met 130 135 140 Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu 145 150 155 160 Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn 165 170 175 Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe 180 185 190 Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro 195 200 205 Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile 210 215 220 Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu 225 230 235 240 Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr 245 250 255 Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu 260 265 270 Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser 275 280 285 Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr 290 295 300 Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe 305 310 315 320 Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr 325 330 335 Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys 340 345 350 Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe 355 360 365 Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr 370 375 380 Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln 385 390 395 400 Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu 405 410 415 Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu 420 425 430 Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg 435 440 445 Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr 450 455 460 Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr 465 470 475 480 Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr 485 490 495 Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro 500 505 510 Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys 515 520 525 Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr 530 535 540 Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile 545 550 555 560 Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu 565 570 575 Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly 580 585 590 Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys 595 600 605 Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp 610 615 620 Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys 625 630 635 640 Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro 645 650 655 Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro 660 665 670 Ser Gly Ala Gly Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met 675 680 685 Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala 690 695 700 Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val 705 710 715 720 Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp 725 730 735 Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr 740 745 750 Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn 755 760 765 Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro 770 775 780 Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro 785 790 795 800 Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys 805 810 815 Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu 820 825 830 Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly 835 840 845 Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr 850 855 860 Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly 865 870 875 880 Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg 885 890 895 Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys 900 905 910 Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser 915 920 925 Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn 930 935 940 Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn 945 950 955 960 Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp 965 970 975 Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu 980 985 990 Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu 995 1000 1005 Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys 1010 1015 1020 Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr 1025 1030 1035 His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe 1040 1045 1050 Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr 1055 1060 1065 Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu 1070 1075 1080 Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg 1085 1090 1095 Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val 1100 1105 1110 Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val 1115 1120 1125 Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu 1130 1135 1140 Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly 1145 1150 1155 Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu 1160 1165 1170 Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu 1175 1180 1185 Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Gly 1190 1195 1200 Ser Gly Arg Glu Asn Leu Tyr Phe Gln Gly Gly Gly Gly Ser Gly 1205 1210 1215 Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys 1220 1225 1230 Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu Gly Gly Ser Gly 1235 1240 1245 Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala 1250 1255 1260 Glu Glu Ala Ala Arg Met Glu Glu Leu Phe Lys Glu His Lys Ile 1265 1270 1275 Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Lys Lys Lys 1280 1285 1290 Ala Leu Ala Val Phe Leu Gly Gly Val Asp Leu Ile Glu Ile Thr 1295 1300 1305 Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Glu Leu Ser Phe 1310 1315 1320 Leu Lys Glu Met Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser 1325 1330 1335 Val Glu Gln Ala Arg Glu Ala Val Glu Ser Gly Ala Glu Phe Ile 1340 1345 1350 Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu 1355 1360 1365 Glu Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu 1370 1375 1380 Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro 1385 1390 1395 Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala Met Lys Gly Pro 1400 1405 1410 Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp 1415 1420 1425 Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly Val 1430 1435 1440 Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys 1445 1450 1455 Ala Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu Gly Gly 1460 1465 1470 Ser His His His His His His His His 1475 1480 <210> 73 <211> 1445 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1242)..(1242) <223> X is absent or is an amino acid linker <400> 73 Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr 1 5 10 15 Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser 20 25 30 Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn 35 40 45 Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys 50 55 60 Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala 65 70 75 80 Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr 85 90 95 Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn 100 105 110 Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln 145 150 155 160 Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu 165 170 175 Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser 180 185 190 Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser 195 200 205 Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg 210 215 220 Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp 225 230 235 240 Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr 245 250 255 Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile 260 265 270 Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 275 280 285 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 290 295 300 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 305 310 315 320 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 325 330 335 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 340 345 350 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 355 360 365 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 370 375 380 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 385 390 395 400 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 405 410 415 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 420 425 430 Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu 435 440 445 Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser 450 455 460 Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln 465 470 475 480 Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys 530 535 540 Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Ser Gly Ala Gly 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Gly Ser Gly Arg Glu 1190 1195 1200 Asn Leu Tyr Phe Gln Gly Gly Gly Gly Ser Gly Tyr Ile Pro Glu 1205 1210 1215 Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp 1220 1225 1230 Val Leu Leu Ser Thr Phe Leu Gly Xaa Met Glu Glu Leu Phe Lys 1235 1240 1245 Glu His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu 1250 1255 1260 Ala Lys Lys Lys Ala Leu Ala Val Phe Leu Gly Gly Val Asp Leu 1265 1270 1275 Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys 1280 1285 1290 Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile Ile Gly Ala Gly 1295 1300 1305 Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val Glu Ser Gly 1310 1315 1320 Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln 1325 1330 1335 Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met Thr 1340 1345 1350 Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu 1355 1360 1365 Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala 1370 1375 1380 Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly 1385 1390 1395 Val Asn Leu Asp Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln 1400 1405 1410 Ala Val Gly Val Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu 1415 1420 1425 Val Ala Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Glu Gly Ala 1430 1435 1440 Thr Glu 1445 <210> 74 <211> 1488 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (1274)..(1274) <223> X is absent or is an amino acid linker <220> <221> MISC_FEATURE <222> (1478)..(1488) <223> optionally absent <400> 74 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr 35 40 45 Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser 50 55 60 Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn 65 70 75 80 Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys 85 90 95 Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala 100 105 110 Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr 115 120 125 Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn 130 135 140 Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu 145 150 155 160 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 165 170 175 Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln 180 185 190 Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu 195 200 205 Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser 210 215 220 Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser 225 230 235 240 Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg 245 250 255 Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp 260 265 270 Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr 275 280 285 Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile 290 295 300 Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 305 310 315 320 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 325 330 335 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 340 345 350 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 355 360 365 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 370 375 380 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 385 390 395 400 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 405 410 415 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 420 425 430 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 435 440 445 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 450 455 460 Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu 465 470 475 480 Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser 485 490 495 Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln 500 505 510 Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg 515 520 525 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 530 535 540 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 545 550 555 560 Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys 565 570 575 Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr 580 585 590 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 595 600 605 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 610 615 620 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 625 630 635 640 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 645 650 655 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 660 665 670 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 675 680 685 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Ser Gly Ala Gly 690 695 700 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 705 710 715 720 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 725 730 735 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 740 745 750 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 755 760 765 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 770 775 780 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 785 790 795 800 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 805 810 815 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 820 825 830 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 835 840 845 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 850 855 860 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 865 870 875 880 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 885 890 895 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 900 905 910 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 915 920 925 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 930 935 940 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 945 950 955 960 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 965 970 975 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 980 985 990 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 995 1000 1005 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu 1010 1015 1020 Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg 1025 1030 1035 Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu 1040 1045 1050 Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu 1055 1060 1065 Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His 1070 1075 1080 Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro 1085 1090 1095 Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val 1100 1105 1110 Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe 1115 1120 1125 Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly 1130 1135 1140 Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp 1145 1150 1155 Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys 1160 1165 1170 Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile 1175 1180 1185 Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp 1190 1195 1200 Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp 1205 1210 1215 Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Gly Ser Gly 1220 1225 1230 Arg Glu Asn Leu Tyr Phe Gln Gly Gly Gly Gly Ser Gly Tyr Ile 1235 1240 1245 Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly 1250 1255 1260 Glu Trp Val Leu Leu Ser Thr Phe Leu Gly Xaa Met Glu Glu Leu 1265 1270 1275 Phe Lys Glu His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val 1280 1285 1290 Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe Leu Gly Gly Val 1295 1300 1305 Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val 1310 1315 1320 Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile Ile Gly 1325 1330 1335 Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val Glu 1340 1345 1350 Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile 1355 1360 1365 Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val 1370 1375 1380 Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr 1385 1390 1395 Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val 1400 1405 1410 Glu Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr 1415 1420 1425 Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Glu Ala Gly 1430 1435 1440 Val Gln Ala Val Gly Val Gly Glu Ala Leu Asn Glu Gly Thr Pro 1445 1450 1455 Val Glu Val Ala Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Glu 1460 1465 1470 Gly Ala Thr Glu Gly Gly Ser His His His His His His His His 1475 1480 1485 <210> 75 <211> 1449 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1246)..(1246) <223> X is absent or is an amino acid linker <400> 75 Glu Thr Gly Thr Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro 1 5 10 15 Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys 20 25 30 Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro 35 40 45 Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr 50 55 60 Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly 65 70 75 80 Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile 85 90 95 Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn 100 105 110 Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn 115 120 125 Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met 130 135 140 Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu 145 150 155 160 Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn 165 170 175 Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe 180 185 190 Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro 195 200 205 Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile 210 215 220 Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu 225 230 235 240 Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr 245 250 255 Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu 260 265 270 Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser 275 280 285 Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr 290 295 300 Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe 305 310 315 320 Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr 325 330 335 Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys 340 345 350 Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe 355 360 365 Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr 370 375 380 Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln 385 390 395 400 Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu 405 410 415 Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu 420 425 430 Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg 435 440 445 Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr 450 455 460 Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr 465 470 475 480 Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr 485 490 495 Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro 500 505 510 Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys 515 520 525 Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr 530 535 540 Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile 545 550 555 560 Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu 565 570 575 Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly 580 585 590 Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys 595 600 605 Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp 610 615 620 Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys 625 630 635 640 Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro 645 650 655 Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro 660 665 670 Ser Gly Ala Gly Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met 675 680 685 Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala 690 695 700 Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val 705 710 715 720 Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp 725 730 735 Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr 740 745 750 Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn 755 760 765 Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro 770 775 780 Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro 785 790 795 800 Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys 805 810 815 Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu 820 825 830 Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly 835 840 845 Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr 850 855 860 Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly 865 870 875 880 Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg 885 890 895 Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys 900 905 910 Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser 915 920 925 Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn 930 935 940 Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn 945 950 955 960 Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp 965 970 975 Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu 980 985 990 Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu 995 1000 1005 Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys 1010 1015 1020 Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr 1025 1030 1035 His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe 1040 1045 1050 Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr 1055 1060 1065 Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu 1070 1075 1080 Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg 1085 1090 1095 Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val 1100 1105 1110 Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val 1115 1120 1125 Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu 1130 1135 1140 Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly 1145 1150 1155 Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu 1160 1165 1170 Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu 1175 1180 1185 Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Gly 1190 1195 1200 Ser Gly Arg Glu Asn Leu Tyr Phe Gln Gly Gly Gly Gly Ser Gly 1205 1210 1215 Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys 1220 1225 1230 Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu Gly Xaa Met Glu 1235 1240 1245 Glu Leu Phe Lys Glu His Lys Ile Val Ala Val Leu Arg Ala Asn 1250 1255 1260 Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe Leu Gly 1265 1270 1275 Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp 1280 1285 1290 Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile 1295 1300 1305 Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala 1310 1315 1320 Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu 1325 1330 1335 Glu Ile Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro 1340 1345 1350 Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly 1355 1360 1365 His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln 1370 1375 1380 Phe Val Glu Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val 1385 1390 1395 Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Glu 1400 1405 1410 Ala Gly Val Gln Ala Val Gly Val Gly Glu Ala Leu Asn Glu Gly 1415 1420 1425 Thr Pro Val Glu Val Ala Glu Lys Ala Lys Ala Phe Val Glu Lys 1430 1435 1440 Ile Glu Gly Ala Thr Glu 1445 <210> 76 <211> 1460 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1246)..(1246) <223> X is absent or is an amino acid linker <220> <221> MISC_FEATURE <222> (1450)..(1460) <223> optionally absent <400> 76 Glu Thr Gly Thr Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro 1 5 10 15 Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys 20 25 30 Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro 35 40 45 Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr 50 55 60 Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly 65 70 75 80 Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile 85 90 95 Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn 100 105 110 Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn 115 120 125 Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met 130 135 140 Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu 145 150 155 160 Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn 165 170 175 Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe 180 185 190 Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro 195 200 205 Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile 210 215 220 Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu 225 230 235 240 Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr 245 250 255 Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu 260 265 270 Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser 275 280 285 Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr 290 295 300 Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe 305 310 315 320 Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr 325 330 335 Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys 340 345 350 Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe 355 360 365 Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr 370 375 380 Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln 385 390 395 400 Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu 405 410 415 Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu 420 425 430 Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg 435 440 445 Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr 450 455 460 Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr 465 470 475 480 Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr 485 490 495 Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro 500 505 510 Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys 515 520 525 Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr 530 535 540 Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile 545 550 555 560 Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu 565 570 575 Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly 580 585 590 Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys 595 600 605 Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp 610 615 620 Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys 625 630 635 640 Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro 645 650 655 Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro 660 665 670 Ser Gly Ala Gly Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met 675 680 685 Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala 690 695 700 Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val 705 710 715 720 Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp 725 730 735 Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr 740 745 750 Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn 755 760 765 Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro 770 775 780 Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro 785 790 795 800 Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys 805 810 815 Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu 820 825 830 Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly 835 840 845 Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr 850 855 860 Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly 865 870 875 880 Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg 885 890 895 Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys 900 905 910 Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser 915 920 925 Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn 930 935 940 Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn 945 950 955 960 Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp 965 970 975 Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu 980 985 990 Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu 995 1000 1005 Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys 1010 1015 1020 Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr 1025 1030 1035 His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe 1040 1045 1050 Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr 1055 1060 1065 Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu 1070 1075 1080 Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg 1085 1090 1095 Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val 1100 1105 1110 Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val 1115 1120 1125 Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu 1130 1135 1140 Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly 1145 1150 1155 Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu 1160 1165 1170 Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu 1175 1180 1185 Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Gly 1190 1195 1200 Ser Gly Arg Glu Asn Leu Tyr Phe Gln Gly Gly Gly Gly Ser Gly 1205 1210 1215 Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys 1220 1225 1230 Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu Gly Xaa Met Glu 1235 1240 1245 Glu Leu Phe Lys Glu His Lys Ile Val Ala Val Leu Arg Ala Asn 1250 1255 1260 Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe Leu Gly 1265 1270 1275 Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp 1280 1285 1290 Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile 1295 1300 1305 Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala 1310 1315 1320 Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu 1325 1330 1335 Glu Ile Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro 1340 1345 1350 Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly 1355 1360 1365 His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln 1370 1375 1380 Phe Val Glu Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val 1385 1390 1395 Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Glu 1400 1405 1410 Ala Gly Val Gln Ala Val Gly Val Gly Glu Ala Leu Asn Glu Gly 1415 1420 1425 Thr Pro Val Glu Val Ala Glu Lys Ala Lys Ala Phe Val Glu Lys 1430 1435 1440 Ile Glu Gly Ala Thr Glu Gly Gly Ser His His His His His His 1445 1450 1455 His His 1460 <210> 77 <211> 1425 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 77 Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr 1 5 10 15 Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser 20 25 30 Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn 35 40 45 Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys 50 55 60 Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala 65 70 75 80 Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr 85 90 95 Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn 100 105 110 Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln 145 150 155 160 Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu 165 170 175 Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser 180 185 190 Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser 195 200 205 Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg 210 215 220 Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp 225 230 235 240 Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr 245 250 255 Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile 260 265 270 Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 275 280 285 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 290 295 300 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 305 310 315 320 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 325 330 335 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 340 345 350 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 355 360 365 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 370 375 380 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 385 390 395 400 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 405 410 415 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 420 425 430 Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu 435 440 445 Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser 450 455 460 Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln 465 470 475 480 Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys 530 535 540 Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Ser Gly Ala Gly 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Gly Ser Gly Ser Gly 1190 1195 1200 Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu 1205 1210 1215 Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Glu His Lys Ile Val 1220 1225 1230 Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala 1235 1240 1245 Leu Ala Val Phe Leu Gly Gly Val Asp Leu Ile Glu Ile Thr Phe 1250 1255 1260 Thr Val Pro Asp Ala Asp Thr Val Ile Lys Glu Leu Ser Phe Leu 1265 1270 1275 Lys Glu Met Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val 1280 1285 1290 Glu Gln Ala Arg Glu Ala Val Glu Ser Gly Ala Glu Phe Ile Val 1295 1300 1305 Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Glu 1310 1315 1320 Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val 1325 1330 1335 Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly 1340 1345 1350 Glu Val Val Gly Pro Gln Phe Val Glu Ala Met Lys Gly Pro Phe 1355 1360 1365 Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn 1370 1375 1380 Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly Val Gly 1385 1390 1395 Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys Ala 1400 1405 1410 Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu 1415 1420 1425 <210> 78 <211> 1468 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (1458)..(1468) <223> optionally absent <400> 78 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr 35 40 45 Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser 50 55 60 Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn 65 70 75 80 Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys 85 90 95 Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala 100 105 110 Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr 115 120 125 Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn 130 135 140 Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu 145 150 155 160 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 165 170 175 Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln 180 185 190 Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu 195 200 205 Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser 210 215 220 Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser 225 230 235 240 Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg 245 250 255 Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp 260 265 270 Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr 275 280 285 Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile 290 295 300 Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 305 310 315 320 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 325 330 335 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 340 345 350 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 355 360 365 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 370 375 380 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 385 390 395 400 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 405 410 415 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 420 425 430 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 435 440 445 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 450 455 460 Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu 465 470 475 480 Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser 485 490 495 Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln 500 505 510 Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg 515 520 525 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 530 535 540 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 545 550 555 560 Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys 565 570 575 Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr 580 585 590 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 595 600 605 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 610 615 620 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 625 630 635 640 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 645 650 655 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 660 665 670 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 675 680 685 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Ser Gly Ala Gly 690 695 700 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 705 710 715 720 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 725 730 735 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 740 745 750 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 755 760 765 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 770 775 780 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 785 790 795 800 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 805 810 815 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 820 825 830 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 835 840 845 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 850 855 860 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 865 870 875 880 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 885 890 895 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 900 905 910 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 915 920 925 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 930 935 940 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 945 950 955 960 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 965 970 975 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 980 985 990 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 995 1000 1005 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu 1010 1015 1020 Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg 1025 1030 1035 Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu 1040 1045 1050 Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu 1055 1060 1065 Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His 1070 1075 1080 Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro 1085 1090 1095 Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val 1100 1105 1110 Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe 1115 1120 1125 Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly 1130 1135 1140 Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp 1145 1150 1155 Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys 1160 1165 1170 Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile 1175 1180 1185 Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp 1190 1195 1200 Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp 1205 1210 1215 Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Gly Ser Gly 1220 1225 1230 Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala 1235 1240 1245 Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Glu His Lys 1250 1255 1260 Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Lys Lys 1265 1270 1275 Lys Ala Leu Ala Val Phe Leu Gly Gly Val Asp Leu Ile Glu Ile 1280 1285 1290 Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Glu Leu Ser 1295 1300 1305 Phe Leu Lys Glu Met Gly Ala Ile Ile Gly Ala Gly Thr Val Thr 1310 1315 1320 Ser Val Glu Gln Ala Arg Glu Ala Val Glu Ser Gly Ala Glu Phe 1325 1330 1335 Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys 1340 1345 1350 Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu 1355 1360 1365 Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe 1370 1375 1380 Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala Met Lys Gly 1385 1390 1395 Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu 1400 1405 1410 Asp Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly 1415 1420 1425 Val Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu 1430 1435 1440 Lys Ala Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu Gly 1445 1450 1455 Gly Ser His His His His His His His His 1460 1465 <210> 79 <211> 1429 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 79 Glu Thr Gly Thr Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro 1 5 10 15 Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys 20 25 30 Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro 35 40 45 Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr 50 55 60 Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly 65 70 75 80 Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile 85 90 95 Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn 100 105 110 Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn 115 120 125 Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met 130 135 140 Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu 145 150 155 160 Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn 165 170 175 Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe 180 185 190 Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro 195 200 205 Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile 210 215 220 Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu 225 230 235 240 Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr 245 250 255 Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu 260 265 270 Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser 275 280 285 Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr 290 295 300 Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe 305 310 315 320 Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr 325 330 335 Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys 340 345 350 Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe 355 360 365 Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr 370 375 380 Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln 385 390 395 400 Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu 405 410 415 Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu 420 425 430 Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg 435 440 445 Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr 450 455 460 Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr 465 470 475 480 Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr 485 490 495 Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro 500 505 510 Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys 515 520 525 Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr 530 535 540 Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile 545 550 555 560 Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu 565 570 575 Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly 580 585 590 Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys 595 600 605 Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp 610 615 620 Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys 625 630 635 640 Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro 645 650 655 Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro 660 665 670 Ser Gly Ala Gly Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met 675 680 685 Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala 690 695 700 Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val 705 710 715 720 Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp 725 730 735 Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr 740 745 750 Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn 755 760 765 Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro 770 775 780 Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro 785 790 795 800 Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys 805 810 815 Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu 820 825 830 Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly 835 840 845 Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr 850 855 860 Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly 865 870 875 880 Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg 885 890 895 Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys 900 905 910 Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser 915 920 925 Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn 930 935 940 Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn 945 950 955 960 Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp 965 970 975 Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu 980 985 990 Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu 995 1000 1005 Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys 1010 1015 1020 Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr 1025 1030 1035 His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe 1040 1045 1050 Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr 1055 1060 1065 Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu 1070 1075 1080 Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg 1085 1090 1095 Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val 1100 1105 1110 Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val 1115 1120 1125 Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu 1130 1135 1140 Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly 1145 1150 1155 Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu 1160 1165 1170 Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu 1175 1180 1185 Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Gly 1190 1195 1200 Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala 1205 1210 1215 Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Glu 1220 1225 1230 His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala 1235 1240 1245 Lys Lys Lys Ala Leu Ala Val Phe Leu Gly Gly Val Asp Leu Ile 1250 1255 1260 Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Glu 1265 1270 1275 Leu Ser Phe Leu Lys Glu Met Gly Ala Ile Ile Gly Ala Gly Thr 1280 1285 1290 Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val Glu Ser Gly Ala 1295 1300 1305 Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe 1310 1315 1320 Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro 1325 1330 1335 Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys 1340 1345 1350 Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala Met 1355 1360 1365 Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val 1370 1375 1380 Asn Leu Asp Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala 1385 1390 1395 Val Gly Val Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val 1400 1405 1410 Ala Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr 1415 1420 1425 Glu <210> 80 <211> 1440 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1430)..(1440) <223> optionally absent <400> 80 Glu Thr Gly Thr Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro 1 5 10 15 Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys 20 25 30 Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro 35 40 45 Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr 50 55 60 Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly 65 70 75 80 Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile 85 90 95 Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn 100 105 110 Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn 115 120 125 Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met 130 135 140 Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu 145 150 155 160 Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn 165 170 175 Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe 180 185 190 Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro 195 200 205 Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile 210 215 220 Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu 225 230 235 240 Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr 245 250 255 Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu 260 265 270 Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser 275 280 285 Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr 290 295 300 Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe 305 310 315 320 Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr 325 330 335 Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys 340 345 350 Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe 355 360 365 Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr 370 375 380 Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln 385 390 395 400 Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu 405 410 415 Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu 420 425 430 Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg 435 440 445 Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr 450 455 460 Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr 465 470 475 480 Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr 485 490 495 Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro 500 505 510 Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys 515 520 525 Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr 530 535 540 Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile 545 550 555 560 Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu 565 570 575 Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly 580 585 590 Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys 595 600 605 Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp 610 615 620 Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys 625 630 635 640 Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro 645 650 655 Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro 660 665 670 Ser Gly Ala Gly Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met 675 680 685 Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala 690 695 700 Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val 705 710 715 720 Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp 725 730 735 Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr 740 745 750 Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn 755 760 765 Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro 770 775 780 Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro 785 790 795 800 Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys 805 810 815 Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu 820 825 830 Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly 835 840 845 Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr 850 855 860 Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly 865 870 875 880 Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg 885 890 895 Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys 900 905 910 Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser 915 920 925 Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn 930 935 940 Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn 945 950 955 960 Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp 965 970 975 Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu 980 985 990 Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu 995 1000 1005 Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys 1010 1015 1020 Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr 1025 1030 1035 His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe 1040 1045 1050 Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr 1055 1060 1065 Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu 1070 1075 1080 Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg 1085 1090 1095 Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val 1100 1105 1110 Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val 1115 1120 1125 Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu 1130 1135 1140 Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly 1145 1150 1155 Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu 1160 1165 1170 Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu 1175 1180 1185 Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Gly 1190 1195 1200 Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala 1205 1210 1215 Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Glu 1220 1225 1230 His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala 1235 1240 1245 Lys Lys Lys Ala Leu Ala Val Phe Leu Gly Gly Val Asp Leu Ile 1250 1255 1260 Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Glu 1265 1270 1275 Leu Ser Phe Leu Lys Glu Met Gly Ala Ile Ile Gly Ala Gly Thr 1280 1285 1290 Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val Glu Ser Gly Ala 1295 1300 1305 Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe 1310 1315 1320 Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro 1325 1330 1335 Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys 1340 1345 1350 Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala Met 1355 1360 1365 Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val 1370 1375 1380 Asn Leu Asp Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala 1385 1390 1395 Val Gly Val Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val 1400 1405 1410 Ala Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr 1415 1420 1425 Glu Gly Gly Ser His His His His His His His His 1430 1435 1440 <210> 81 <211> 1402 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1199)..(1199) <223> X is absent or is an amino acid linker <400> 81 Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr 1 5 10 15 Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser 20 25 30 Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn 35 40 45 Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys 50 55 60 Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala 65 70 75 80 Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr 85 90 95 Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn 100 105 110 Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln 145 150 155 160 Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu 165 170 175 Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser 180 185 190 Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser 195 200 205 Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg 210 215 220 Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp 225 230 235 240 Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr 245 250 255 Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile 260 265 270 Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 275 280 285 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 290 295 300 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 305 310 315 320 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 325 330 335 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 340 345 350 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 355 360 365 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 370 375 380 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 385 390 395 400 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 405 410 415 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 420 425 430 Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu 435 440 445 Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser 450 455 460 Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln 465 470 475 480 Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys 530 535 540 Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Ser Gly Ala Gly 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Xaa Met Glu Glu Leu 1190 1195 1200 Phe Lys Glu His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val 1205 1210 1215 Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe Leu Gly Gly Val 1220 1225 1230 Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val 1235 1240 1245 Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile Ile Gly 1250 1255 1260 Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val Glu 1265 1270 1275 Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile 1280 1285 1290 Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val 1295 1300 1305 Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr 1310 1315 1320 Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val 1325 1330 1335 Glu Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr 1340 1345 1350 Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Glu Ala Gly 1355 1360 1365 Val Gln Ala Val Gly Val Gly Glu Ala Leu Asn Glu Gly Thr Pro 1370 1375 1380 Val Glu Val Ala Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Glu 1385 1390 1395 Gly Ala Thr Glu 1400 <210> 82 <211> 1445 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (1231)..(1231) <223> X is absent or is an amino acid linker <220> <221> MISC_FEATURE <222> (1435)..(1445) <223> optionally absent <400> 82 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr 35 40 45 Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser 50 55 60 Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn 65 70 75 80 Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys 85 90 95 Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala 100 105 110 Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr 115 120 125 Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn 130 135 140 Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu 145 150 155 160 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 165 170 175 Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln 180 185 190 Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu 195 200 205 Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser 210 215 220 Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser 225 230 235 240 Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg 245 250 255 Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp 260 265 270 Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr 275 280 285 Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile 290 295 300 Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 305 310 315 320 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 325 330 335 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 340 345 350 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 355 360 365 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 370 375 380 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 385 390 395 400 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 405 410 415 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 420 425 430 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 435 440 445 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 450 455 460 Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu 465 470 475 480 Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser 485 490 495 Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln 500 505 510 Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg 515 520 525 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 530 535 540 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 545 550 555 560 Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys 565 570 575 Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr 580 585 590 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 595 600 605 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 610 615 620 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 625 630 635 640 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 645 650 655 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 660 665 670 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 675 680 685 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Ser Gly Ala Gly 690 695 700 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 705 710 715 720 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 725 730 735 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 740 745 750 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 755 760 765 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 770 775 780 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 785 790 795 800 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 805 810 815 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 820 825 830 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 835 840 845 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 850 855 860 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 865 870 875 880 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 885 890 895 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 900 905 910 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 915 920 925 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 930 935 940 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 945 950 955 960 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 965 970 975 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 980 985 990 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 995 1000 1005 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu 1010 1015 1020 Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg 1025 1030 1035 Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu 1040 1045 1050 Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu 1055 1060 1065 Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His 1070 1075 1080 Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro 1085 1090 1095 Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val 1100 1105 1110 Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe 1115 1120 1125 Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly 1130 1135 1140 Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp 1145 1150 1155 Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys 1160 1165 1170 Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile 1175 1180 1185 Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp 1190 1195 1200 Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp 1205 1210 1215 Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Xaa Met Glu 1220 1225 1230 Glu Leu Phe Lys Glu His Lys Ile Val Ala Val Leu Arg Ala Asn 1235 1240 1245 Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe Leu Gly 1250 1255 1260 Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp 1265 1270 1275 Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile 1280 1285 1290 Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala 1295 1300 1305 Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu 1310 1315 1320 Glu Ile Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro 1325 1330 1335 Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly 1340 1345 1350 His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln 1355 1360 1365 Phe Val Glu Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val 1370 1375 1380 Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Glu 1385 1390 1395 Ala Gly Val Gln Ala Val Gly Val Gly Glu Ala Leu Asn Glu Gly 1400 1405 1410 Thr Pro Val Glu Val Ala Glu Lys Ala Lys Ala Phe Val Glu Lys 1415 1420 1425 Ile Glu Gly Ala Thr Glu Gly Gly Ser His His His His His His 1430 1435 1440 His His 1445 <210> 83 <211> 1406 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1203)..(1203) <223> X is absent or is an amino acid linker <400> 83 Glu Thr Gly Thr Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro 1 5 10 15 Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys 20 25 30 Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro 35 40 45 Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr 50 55 60 Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly 65 70 75 80 Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile 85 90 95 Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn 100 105 110 Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn 115 120 125 Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met 130 135 140 Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu 145 150 155 160 Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn 165 170 175 Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe 180 185 190 Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro 195 200 205 Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile 210 215 220 Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu 225 230 235 240 Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr 245 250 255 Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu 260 265 270 Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser 275 280 285 Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr 290 295 300 Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe 305 310 315 320 Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr 325 330 335 Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys 340 345 350 Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe 355 360 365 Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr 370 375 380 Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln 385 390 395 400 Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu 405 410 415 Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu 420 425 430 Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg 435 440 445 Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr 450 455 460 Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr 465 470 475 480 Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr 485 490 495 Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro 500 505 510 Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys 515 520 525 Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr 530 535 540 Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile 545 550 555 560 Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu 565 570 575 Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly 580 585 590 Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys 595 600 605 Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp 610 615 620 Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys 625 630 635 640 Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro 645 650 655 Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro 660 665 670 Ser Gly Ala Gly Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met 675 680 685 Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala 690 695 700 Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val 705 710 715 720 Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp 725 730 735 Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr 740 745 750 Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn 755 760 765 Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro 770 775 780 Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro 785 790 795 800 Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys 805 810 815 Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu 820 825 830 Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly 835 840 845 Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr 850 855 860 Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly 865 870 875 880 Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg 885 890 895 Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys 900 905 910 Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser 915 920 925 Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn 930 935 940 Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn 945 950 955 960 Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp 965 970 975 Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu 980 985 990 Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu 995 1000 1005 Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys 1010 1015 1020 Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr 1025 1030 1035 His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe 1040 1045 1050 Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr 1055 1060 1065 Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu 1070 1075 1080 Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg 1085 1090 1095 Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val 1100 1105 1110 Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val 1115 1120 1125 Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu 1130 1135 1140 Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly 1145 1150 1155 Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu 1160 1165 1170 Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu 1175 1180 1185 Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Xaa 1190 1195 1200 Met Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala Val Leu Arg 1205 1210 1215 Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe 1220 1225 1230 Leu Gly Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp 1235 1240 1245 Ala Asp Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly 1250 1255 1260 Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg 1265 1270 1275 Glu Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu 1280 1285 1290 Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr 1295 1300 1305 Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys 1310 1315 1320 Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly 1325 1330 1335 Pro Gln Phe Val Glu Ala Met Lys Gly Pro Phe Pro Asn Val Lys 1340 1345 1350 Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp 1355 1360 1365 Phe Glu Ala Gly Val Gln Ala Val Gly Val Gly Glu Ala Leu Asn 1370 1375 1380 Glu Gly Thr Pro Val Glu Val Ala Glu Lys Ala Lys Ala Phe Val 1385 1390 1395 Glu Lys Ile Glu Gly Ala Thr Glu 1400 1405 <210> 84 <211> 1417 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1203)..(1203) <223> X is absent or is an amino acid linker <220> <221> MISC_FEATURE <222> (1407)..(1417) <223> optionally absent <400> 84 Glu Thr Gly Thr Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro 1 5 10 15 Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys 20 25 30 Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro 35 40 45 Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr 50 55 60 Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly 65 70 75 80 Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile 85 90 95 Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn 100 105 110 Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn 115 120 125 Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met 130 135 140 Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu 145 150 155 160 Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn 165 170 175 Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe 180 185 190 Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro 195 200 205 Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile 210 215 220 Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu 225 230 235 240 Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr 245 250 255 Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu 260 265 270 Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser 275 280 285 Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr 290 295 300 Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe 305 310 315 320 Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr 325 330 335 Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys 340 345 350 Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe 355 360 365 Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr 370 375 380 Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln 385 390 395 400 Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu 405 410 415 Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu 420 425 430 Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg 435 440 445 Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr 450 455 460 Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr 465 470 475 480 Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr 485 490 495 Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro 500 505 510 Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys 515 520 525 Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr 530 535 540 Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile 545 550 555 560 Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu 565 570 575 Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly 580 585 590 Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys 595 600 605 Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp 610 615 620 Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys 625 630 635 640 Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro 645 650 655 Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro 660 665 670 Ser Gly Ala Gly Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met 675 680 685 Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala 690 695 700 Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val 705 710 715 720 Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp 725 730 735 Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr 740 745 750 Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn 755 760 765 Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro 770 775 780 Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro 785 790 795 800 Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys 805 810 815 Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu 820 825 830 Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly 835 840 845 Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr 850 855 860 Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly 865 870 875 880 Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg 885 890 895 Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys 900 905 910 Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser 915 920 925 Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn 930 935 940 Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn 945 950 955 960 Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp 965 970 975 Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu 980 985 990 Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu 995 1000 1005 Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys 1010 1015 1020 Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr 1025 1030 1035 His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe 1040 1045 1050 Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr 1055 1060 1065 Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu 1070 1075 1080 Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg 1085 1090 1095 Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val 1100 1105 1110 Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val 1115 1120 1125 Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu 1130 1135 1140 Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly 1145 1150 1155 Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu 1160 1165 1170 Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu 1175 1180 1185 Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Xaa 1190 1195 1200 Met Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala Val Leu Arg 1205 1210 1215 Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe 1220 1225 1230 Leu Gly Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp 1235 1240 1245 Ala Asp Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly 1250 1255 1260 Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg 1265 1270 1275 Glu Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu 1280 1285 1290 Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr 1295 1300 1305 Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys 1310 1315 1320 Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly 1325 1330 1335 Pro Gln Phe Val Glu Ala Met Lys Gly Pro Phe Pro Asn Val Lys 1340 1345 1350 Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp 1355 1360 1365 Phe Glu Ala Gly Val Gln Ala Val Gly Val Gly Glu Ala Leu Asn 1370 1375 1380 Glu Gly Thr Pro Val Glu Val Ala Glu Lys Ala Lys Ala Phe Val 1385 1390 1395 Glu Lys Ile Glu Gly Ala Thr Glu Gly Gly Ser His His His His 1400 1405 1410 His His His His 1415 <210> 85 <211> 232 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <400> 85 Xaa Gly Gly Ser Gly Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly 1 5 10 15 Ser Glu Lys Ala Ala Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu 20 25 30 Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val 35 40 45 Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val His 50 55 60 Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys 65 70 75 80 Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr 85 90 95 Val Thr Ser Val Glu Gln Ala Arg Lys Ala Val Glu Ser Gly Ala Glu 100 105 110 Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys 115 120 125 Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu 130 135 140 Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly 145 150 155 160 Glu Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro 165 170 175 Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala 180 185 190 Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu 195 200 205 Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val 210 215 220 Glu Lys Ile Arg Gly Ala Thr Glu 225 230 <210> 86 <211> 206 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <220> <221> MISC_FEATURE <222> (2)..(2) <223> X is absent or an amino acid linker <400> 86 Xaa Xaa Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val 1 5 10 15 Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val 20 25 30 Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp 35 40 45 Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala 50 55 60 Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala 65 70 75 80 Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu 85 90 95 Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val 100 105 110 Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile 115 120 125 Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala 130 135 140 Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val 145 150 155 160 Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val 165 170 175 Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu 180 185 190 Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu 195 200 205 <210> 87 <211> 243 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <220> <221> MISC_FEATURE <222> (233)..(243) <223> optionally absent <400> 87 Xaa Gly Gly Ser Gly Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly 1 5 10 15 Ser Glu Lys Ala Ala Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu 20 25 30 Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val 35 40 45 Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val His 50 55 60 Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys 65 70 75 80 Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr 85 90 95 Val Thr Ser Val Glu Gln Ala Arg Lys Ala Val Glu Ser Gly Ala Glu 100 105 110 Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys 115 120 125 Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu 130 135 140 Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly 145 150 155 160 Glu Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro 165 170 175 Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala 180 185 190 Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu 195 200 205 Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val 210 215 220 Glu Lys Ile Arg Gly Ala Thr Glu Gly Gly Ser His His His His His 225 230 235 240 His His His <210> 88 <211> 217 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <220> <221> MISC_FEATURE <222> (2)..(2) <223> X is absent or an amino acid linker <220> <221> MISC_FEATURE <222> (207)..(217) <223> optionally absent <400> 88 Xaa Xaa Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val 1 5 10 15 Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val 20 25 30 Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp 35 40 45 Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala 50 55 60 Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala 65 70 75 80 Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu 85 90 95 Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val 100 105 110 Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile 115 120 125 Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala 130 135 140 Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val 145 150 155 160 Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val 165 170 175 Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu 180 185 190 Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu Gly Gly 195 200 205 Ser His His His His His His His His 210 215 <210> 89 <211> 224 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <400> 89 Xaa Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu 1 5 10 15 Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val 20 25 30 Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val 35 40 45 Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val 50 55 60 Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys 65 70 75 80 Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg 85 90 95 Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp 100 105 110 Glu Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro 115 120 125 Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His 130 135 140 Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val 145 150 155 160 Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly 165 170 175 Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu 180 185 190 Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val 195 200 205 Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu 210 215 220 <210> 90 <211> 206 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <220> <221> MISC_FEATURE <222> (2)..(2) <223> X is absent or an amino acid linker <400> 90 Xaa Xaa Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val 1 5 10 15 Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val 20 25 30 Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp 35 40 45 Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala 50 55 60 Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala 65 70 75 80 Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu 85 90 95 Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val 100 105 110 Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile 115 120 125 Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala 130 135 140 Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val 145 150 155 160 Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val 165 170 175 Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu 180 185 190 Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu 195 200 205 <210> 91 <211> 235 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <220> <221> MISC_FEATURE <222> (225)..(235) <223> optionally absent <400> 91 Xaa Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu 1 5 10 15 Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val 20 25 30 Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val 35 40 45 Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val 50 55 60 Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys 65 70 75 80 Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg 85 90 95 Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp 100 105 110 Glu Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro 115 120 125 Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His 130 135 140 Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val 145 150 155 160 Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly 165 170 175 Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu 180 185 190 Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val 195 200 205 Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu 210 215 220 Gly Gly Ser His His His His His His His His 225 230 235 <210> 92 <211> 217 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <220> <221> MISC_FEATURE <222> (2)..(2) <223> X is absent or an amino acid linker <220> <221> MISC_FEATURE <222> (207)..(217) <223> optionally absent <400> 92 Xaa Xaa Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val 1 5 10 15 Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val 20 25 30 Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp 35 40 45 Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala 50 55 60 Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala 65 70 75 80 Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu 85 90 95 Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val 100 105 110 Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile 115 120 125 Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala 130 135 140 Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val 145 150 155 160 Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val 165 170 175 Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu 180 185 190 Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu Gly Gly 195 200 205 Ser His His His His His His His His 210 215 <210> 93 <211> 228 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <400> 93 Xaa Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala 1 5 10 15 Ala Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys 20 25 30 His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile 35 40 45 Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile 50 55 60 Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val 65 70 75 80 Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val 85 90 95 Glu Gln Ala Arg Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser 100 105 110 Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val 115 120 125 Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met 130 135 140 Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly 145 150 155 160 Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe 165 170 175 Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys 180 185 190 Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr 195 200 205 Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg 210 215 220 Gly Ala Thr Glu 225 <210> 94 <211> 206 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <220> <221> MISC_FEATURE <222> (2)..(2) <223> X is absent or an amino acid linker <400> 94 Xaa Xaa Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val 1 5 10 15 Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val 20 25 30 Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp 35 40 45 Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala 50 55 60 Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala 65 70 75 80 Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu 85 90 95 Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val 100 105 110 Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile 115 120 125 Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala 130 135 140 Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val 145 150 155 160 Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val 165 170 175 Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu 180 185 190 Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu 195 200 205 <210> 95 <211> 239 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <220> <221> MISC_FEATURE <222> (229)..(239) <223> optionally absent <400> 95 Xaa Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala 1 5 10 15 Ala Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys 20 25 30 His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile 35 40 45 Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile 50 55 60 Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val 65 70 75 80 Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val 85 90 95 Glu Gln Ala Arg Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser 100 105 110 Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val 115 120 125 Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met 130 135 140 Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly 145 150 155 160 Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe 165 170 175 Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys 180 185 190 Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr 195 200 205 Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg 210 215 220 Gly Ala Thr Glu Gly Gly Ser His His His His His His His His 225 230 235 <210> 96 <211> 217 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <220> <221> MISC_FEATURE <222> (2)..(2) <223> X is absent or an amino acid linker <220> <221> MISC_FEATURE <222> (207)..(217) <223> optionally absent <400> 96 Xaa Xaa Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val 1 5 10 15 Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val 20 25 30 Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp 35 40 45 Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala 50 55 60 Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala 65 70 75 80 Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu 85 90 95 Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val 100 105 110 Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile 115 120 125 Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala 130 135 140 Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val 145 150 155 160 Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val 165 170 175 Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu 180 185 190 Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu Gly Gly 195 200 205 Ser His His His His His His His His 210 215 <210> 97 <211> 271 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <400> 97 Xaa Gly Ser Gly Arg Glu Asn Leu Tyr Phe Gln Gly Gly Gly Gly Ser 1 5 10 15 Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys 20 25 30 Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu Gly Gly Ser Gly Ser 35 40 45 Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu 50 55 60 Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala 65 70 75 80 Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala 85 90 95 Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro 100 105 110 Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly 115 120 125 Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys 130 135 140 Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu 145 150 155 160 Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly 165 170 175 Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr 180 185 190 Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys 195 200 205 Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly 210 215 220 Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala 225 230 235 240 Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg 245 250 255 Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu 260 265 270 <210> 98 <211> 206 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <220> <221> MISC_FEATURE <222> (2)..(2) <223> X is absent or an amino acid linker <400> 98 Xaa Xaa Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val 1 5 10 15 Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val 20 25 30 Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp 35 40 45 Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala 50 55 60 Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala 65 70 75 80 Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu 85 90 95 Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val 100 105 110 Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile 115 120 125 Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala 130 135 140 Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val 145 150 155 160 Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val 165 170 175 Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu 180 185 190 Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu 195 200 205 <210> 99 <211> 282 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <220> <221> MISC_FEATURE <222> (272)..(282) <223> optionally absent <400> 99 Xaa Gly Ser Gly Arg Glu Asn Leu Tyr Phe Gln Gly Gly Gly Gly Ser 1 5 10 15 Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys 20 25 30 Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu Gly Gly Ser Gly Ser 35 40 45 Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu 50 55 60 Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala 65 70 75 80 Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala 85 90 95 Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro 100 105 110 Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly 115 120 125 Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys 130 135 140 Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu 145 150 155 160 Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly 165 170 175 Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr 180 185 190 Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys 195 200 205 Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly 210 215 220 Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala 225 230 235 240 Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg 245 250 255 Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu Gly 260 265 270 Gly Ser His His His His His His His His 275 280 <210> 100 <211> 217 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <220> <221> MISC_FEATURE <222> (2)..(2) <223> X is absent or an amino acid linker <220> <221> MISC_FEATURE <222> (207)..(217) <223> optionally absent <400> 100 Xaa Xaa Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val 1 5 10 15 Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val 20 25 30 Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp 35 40 45 Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala 50 55 60 Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala 65 70 75 80 Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu 85 90 95 Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val 100 105 110 Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile 115 120 125 Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala 130 135 140 Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val 145 150 155 160 Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val 165 170 175 Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu 180 185 190 Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu Gly Gly 195 200 205 Ser His His His His His His His His 210 215 <210> 101 <211> 228 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <400> 101 Xaa Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala 1 5 10 15 Ala Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys 20 25 30 His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile 35 40 45 Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile 50 55 60 Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val 65 70 75 80 Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val 85 90 95 Glu Gln Ala Arg Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser 100 105 110 Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val 115 120 125 Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met 130 135 140 Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly 145 150 155 160 Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe 165 170 175 Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys 180 185 190 Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr 195 200 205 Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg 210 215 220 Gly Ala Thr Glu 225 <210> 102 <211> 206 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <220> <221> MISC_FEATURE <222> (2)..(2) <223> X is absent or an amino acid linker <400> 102 Xaa Xaa Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val 1 5 10 15 Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val 20 25 30 Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp 35 40 45 Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala 50 55 60 Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala 65 70 75 80 Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu 85 90 95 Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val 100 105 110 Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile 115 120 125 Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala 130 135 140 Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val 145 150 155 160 Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val 165 170 175 Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu 180 185 190 Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu 195 200 205 <210> 103 <211> 239 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <220> <221> MISC_FEATURE <222> (229)..(239) <223> optionally absent <400> 103 Xaa Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala 1 5 10 15 Ala Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys 20 25 30 His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile 35 40 45 Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile 50 55 60 Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val 65 70 75 80 Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val 85 90 95 Glu Gln Ala Arg Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser 100 105 110 Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val 115 120 125 Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met 130 135 140 Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly 145 150 155 160 Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe 165 170 175 Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys 180 185 190 Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr 195 200 205 Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg 210 215 220 Gly Ala Thr Glu Gly Gly Ser His His His His His His His His 225 230 235 <210> 104 <211> 218 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <220> <221> MISC_FEATURE <222> (2)..(2) <223> X is absent or an amino acid linker <220> <221> MISC_FEATURE <222> (208)..(218) <223> optionally absent <400> 104 Xaa Xaa Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala 1 5 10 15 Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala 20 25 30 Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro 35 40 45 Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly 50 55 60 Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys 65 70 75 80 Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu 85 90 95 Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly 100 105 110 Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr 115 120 125 Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys 130 135 140 Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly 145 150 155 160 Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala 165 170 175 Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg 180 185 190 Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu Gly 195 200 205 Gly Ser His His His His His His His His 210 215 <210> 105 <211> 223 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <400> 105 Xaa Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu 1 5 10 15 Glu Ala Ala Arg Met Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala 20 25 30 Val Leu Arg Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala 35 40 45 Val Phe Leu Gly Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro 50 55 60 Asp Ala Asp Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly 65 70 75 80 Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu 85 90 95 Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu 100 105 110 Glu Ile Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly 115 120 125 Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr 130 135 140 Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu 145 150 155 160 Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly 165 170 175 Val Asn Leu Asp Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala 180 185 190 Val Gly Val Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala 195 200 205 Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu 210 215 220 <210> 106 <211> 205 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <220> <221> MISC_FEATURE <222> (2)..(2) <223> X is absent or an amino acid linker <400> 106 Xaa Xaa Met Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala Val Leu 1 5 10 15 Arg Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe 20 25 30 Leu Gly Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala 35 40 45 Asp Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile 50 55 60 Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val 65 70 75 80 Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile 85 90 95 Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met 100 105 110 Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu 115 120 125 Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala Met 130 135 140 Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn 145 150 155 160 Leu Asp Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly 165 170 175 Val Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys 180 185 190 Ala Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu 195 200 205 <210> 107 <211> 234 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <220> <221> MISC_FEATURE <222> (224)..(234) <223> optionally absent <400> 107 Xaa Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu 1 5 10 15 Glu Ala Ala Arg Met Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala 20 25 30 Val Leu Arg Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala 35 40 45 Val Phe Leu Gly Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro 50 55 60 Asp Ala Asp Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly 65 70 75 80 Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu 85 90 95 Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu 100 105 110 Glu Ile Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly 115 120 125 Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr 130 135 140 Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu 145 150 155 160 Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly 165 170 175 Val Asn Leu Asp Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala 180 185 190 Val Gly Val Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala 195 200 205 Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu Gly 210 215 220 Gly Ser His His His His His His His His 225 230 <210> 108 <211> 216 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <220> <221> MISC_FEATURE <222> (2)..(2) <223> X is absent or an amino acid linker <220> <221> MISC_FEATURE <222> (206)..(216) <223> optionally absent <400> 108 Xaa Xaa Met Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala Val Leu 1 5 10 15 Arg Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe 20 25 30 Leu Gly Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala 35 40 45 Asp Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile 50 55 60 Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val 65 70 75 80 Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile 85 90 95 Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met 100 105 110 Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu 115 120 125 Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala Met 130 135 140 Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn 145 150 155 160 Leu Asp Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly 165 170 175 Val Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys 180 185 190 Ala Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu Gly Gly Ser 195 200 205 His His His His His His His His 210 215 <210> 109 <211> 227 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <400> 109 Xaa Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala 1 5 10 15 Ala Lys Ala Glu Glu Ala Ala Arg Met Glu Glu Leu Phe Lys Glu His 20 25 30 Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Lys Lys 35 40 45 Lys Ala Leu Ala Val Phe Leu Gly Gly Val Asp Leu Ile Glu Ile Thr 50 55 60 Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Glu Leu Ser Phe Leu 65 70 75 80 Lys Glu Met Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu 85 90 95 Gln Ala Arg Glu Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro 100 105 110 His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Glu Gly Val Phe 115 120 125 Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys 130 135 140 Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro 145 150 155 160 Gln Phe Val Glu Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val 165 170 175 Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Glu Ala 180 185 190 Gly Val Gln Ala Val Gly Val Gly Glu Ala Leu Asn Glu Gly Thr Pro 195 200 205 Val Glu Val Ala Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Glu Gly 210 215 220 Ala Thr Glu 225 <210> 110 <211> 204 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <220> <221> MISC_FEATURE <222> (2)..(2) <223> X is absent or an amino acid linker <400> 110 Xaa Met Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala Val Leu Arg 1 5 10 15 Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe Leu 20 25 30 Gly Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp 35 40 45 Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile Ile 50 55 60 Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val Glu 65 70 75 80 Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser 85 90 95 Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met Thr 100 105 110 Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys 115 120 125 Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala Met Lys 130 135 140 Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu 145 150 155 160 Asp Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly Val 165 170 175 Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys Ala 180 185 190 Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu 195 200 <210> 111 <211> 238 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <220> <221> MISC_FEATURE <222> (228)..(238) <223> optionally absent <400> 111 Xaa Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala 1 5 10 15 Ala Lys Ala Glu Glu Ala Ala Arg Met Glu Glu Leu Phe Lys Glu His 20 25 30 Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Lys Lys 35 40 45 Lys Ala Leu Ala Val Phe Leu Gly Gly Val Asp Leu Ile Glu Ile Thr 50 55 60 Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Glu Leu Ser Phe Leu 65 70 75 80 Lys Glu Met Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu 85 90 95 Gln Ala Arg Glu Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro 100 105 110 His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Glu Gly Val Phe 115 120 125 Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys 130 135 140 Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro 145 150 155 160 Gln Phe Val Glu Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val 165 170 175 Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Glu Ala 180 185 190 Gly Val Gln Ala Val Gly Val Gly Glu Ala Leu Asn Glu Gly Thr Pro 195 200 205 Val Glu Val Ala Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Glu Gly 210 215 220 Ala Thr Glu Gly Gly Ser His His His His His His His His 225 230 235 <210> 112 <211> 216 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <220> <221> MISC_FEATURE <222> (2)..(2) <223> X is absent or an amino acid linker <220> <221> MISC_FEATURE <222> (206)..(216) <223> optionally absent <400> 112 Xaa Xaa Met Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala Val Leu 1 5 10 15 Arg Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe 20 25 30 Leu Gly Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala 35 40 45 Asp Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile 50 55 60 Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val 65 70 75 80 Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile 85 90 95 Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met 100 105 110 Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu 115 120 125 Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala Met 130 135 140 Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn 145 150 155 160 Leu Asp Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly 165 170 175 Val Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys 180 185 190 Ala Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu Gly Gly Ser 195 200 205 His His His His His His His His 210 215 <210> 113 <211> 231 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <400> 113 Xaa Gly Gly Ser Gly Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly 1 5 10 15 Ser Glu Lys Ala Ala Lys Ala Glu Glu Ala Ala Arg Met Glu Glu Leu 20 25 30 Phe Lys Glu His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu 35 40 45 Glu Ala Lys Lys Lys Ala Leu Ala Val Phe Leu Gly Gly Val Asp Leu 50 55 60 Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Glu 65 70 75 80 Leu Ser Phe Leu Lys Glu Met Gly Ala Ile Ile Gly Ala Gly Thr Val 85 90 95 Thr Ser Val Glu Gln Ala Arg Glu Ala Val Glu Ser Gly Ala Glu Phe 100 105 110 Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu 115 120 125 Glu Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val 130 135 140 Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu 145 150 155 160 Val Val Gly Pro Gln Phe Val Glu Ala Met Lys Gly Pro Phe Pro Asn 165 170 175 Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu 180 185 190 Trp Phe Glu Ala Gly Val Gln Ala Val Gly Val Gly Glu Ala Leu Asn 195 200 205 Glu Gly Thr Pro Val Glu Val Ala Glu Lys Ala Lys Ala Phe Val Glu 210 215 220 Lys Ile Glu Gly Ala Thr Glu 225 230 <210> 114 <211> 205 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <220> <221> MISC_FEATURE <222> (2)..(2) <223> X is absent or an amino acid linker <400> 114 Xaa Xaa Met Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala Val Leu 1 5 10 15 Arg Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe 20 25 30 Leu Gly Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala 35 40 45 Asp Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile 50 55 60 Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val 65 70 75 80 Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile 85 90 95 Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met 100 105 110 Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu 115 120 125 Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala Met 130 135 140 Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn 145 150 155 160 Leu Asp Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly 165 170 175 Val Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys 180 185 190 Ala Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu 195 200 205 <210> 115 <211> 242 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <220> <221> MISC_FEATURE <222> (232)..(242) <223> optionally absent <400> 115 Xaa Gly Gly Ser Gly Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly 1 5 10 15 Ser Glu Lys Ala Ala Lys Ala Glu Glu Ala Ala Arg Met Glu Glu Leu 20 25 30 Phe Lys Glu His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu 35 40 45 Glu Ala Lys Lys Lys Ala Leu Ala Val Phe Leu Gly Gly Val Asp Leu 50 55 60 Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Glu 65 70 75 80 Leu Ser Phe Leu Lys Glu Met Gly Ala Ile Ile Gly Ala Gly Thr Val 85 90 95 Thr Ser Val Glu Gln Ala Arg Glu Ala Val Glu Ser Gly Ala Glu Phe 100 105 110 Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu 115 120 125 Glu Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val 130 135 140 Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu 145 150 155 160 Val Val Gly Pro Gln Phe Val Glu Ala Met Lys Gly Pro Phe Pro Asn 165 170 175 Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu 180 185 190 Trp Phe Glu Ala Gly Val Gln Ala Val Gly Val Gly Glu Ala Leu Asn 195 200 205 Glu Gly Thr Pro Val Glu Val Ala Glu Lys Ala Lys Ala Phe Val Glu 210 215 220 Lys Ile Glu Gly Ala Thr Glu Gly Gly Ser His His His His His His 225 230 235 240 His His <210> 116 <211> 216 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <220> <221> MISC_FEATURE <222> (2)..(2) <223> X is absent or an amino acid linker <220> <221> MISC_FEATURE <222> (206)..(216) <223> optionally absent <400> 116 Xaa Xaa Met Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala Val Leu 1 5 10 15 Arg Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe 20 25 30 Leu Gly Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala 35 40 45 Asp Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile 50 55 60 Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val 65 70 75 80 Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile 85 90 95 Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met 100 105 110 Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu 115 120 125 Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala Met 130 135 140 Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn 145 150 155 160 Leu Asp Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly 165 170 175 Val Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys 180 185 190 Ala Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu Gly Gly Ser 195 200 205 His His His His His His His His 210 215 <210> 117 <211> 270 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <400> 117 Xaa Gly Ser Gly Arg Glu Asn Leu Tyr Phe Gln Gly Gly Gly Gly Ser 1 5 10 15 Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys 20 25 30 Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu Gly Gly Ser Gly Ser 35 40 45 Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu 50 55 60 Ala Ala Arg Met Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala Val 65 70 75 80 Leu Arg Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val 85 90 95 Phe Leu Gly Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp 100 105 110 Ala Asp Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala 115 120 125 Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala 130 135 140 Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu 145 150 155 160 Ile Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val 165 170 175 Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile 180 185 190 Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala 195 200 205 Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val 210 215 220 Asn Leu Asp Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val 225 230 235 240 Gly Val Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu 245 250 255 Lys Ala Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu 260 265 270 <210> 118 <211> 205 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <220> <221> MISC_FEATURE <222> (2)..(2) <223> X is absent or an amino acid linker <400> 118 Xaa Xaa Met Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala Val Leu 1 5 10 15 Arg Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe 20 25 30 Leu Gly Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala 35 40 45 Asp Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile 50 55 60 Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val 65 70 75 80 Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile 85 90 95 Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met 100 105 110 Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu 115 120 125 Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala Met 130 135 140 Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn 145 150 155 160 Leu Asp Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly 165 170 175 Val Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys 180 185 190 Ala Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu 195 200 205 <210> 119 <211> 281 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <220> <221> MISC_FEATURE <222> (271)..(281) <223> optionally absent <400> 119 Xaa Gly Ser Gly Arg Glu Asn Leu Tyr Phe Gln Gly Gly Gly Gly Ser 1 5 10 15 Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys 20 25 30 Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu Gly Gly Ser Gly Ser 35 40 45 Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu 50 55 60 Ala Ala Arg Met Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala Val 65 70 75 80 Leu Arg Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val 85 90 95 Phe Leu Gly Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp 100 105 110 Ala Asp Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala 115 120 125 Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala 130 135 140 Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu 145 150 155 160 Ile Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val 165 170 175 Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile 180 185 190 Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala 195 200 205 Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val 210 215 220 Asn Leu Asp Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val 225 230 235 240 Gly Val Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu 245 250 255 Lys Ala Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu Gly Gly 260 265 270 Ser His His His His His His His His 275 280 <210> 120 <211> 216 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <220> <221> MISC_FEATURE <222> (2)..(2) <223> X is absent or an amino acid linker <220> <221> MISC_FEATURE <222> (206)..(216) <223> optionally absent <400> 120 Xaa Xaa Met Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala Val Leu 1 5 10 15 Arg Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe 20 25 30 Leu Gly Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala 35 40 45 Asp Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile 50 55 60 Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val 65 70 75 80 Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile 85 90 95 Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met 100 105 110 Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu 115 120 125 Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala Met 130 135 140 Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn 145 150 155 160 Leu Asp Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly 165 170 175 Val Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys 180 185 190 Ala Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu Gly Gly Ser 195 200 205 His His His His His His His His 210 215 <210> 121 <211> 227 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <400> 121 Xaa Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala 1 5 10 15 Ala Lys Ala Glu Glu Ala Ala Arg Met Glu Glu Leu Phe Lys Glu His 20 25 30 Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Lys Lys 35 40 45 Lys Ala Leu Ala Val Phe Leu Gly Gly Val Asp Leu Ile Glu Ile Thr 50 55 60 Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Glu Leu Ser Phe Leu 65 70 75 80 Lys Glu Met Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu 85 90 95 Gln Ala Arg Glu Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro 100 105 110 His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Glu Gly Val Phe 115 120 125 Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys 130 135 140 Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro 145 150 155 160 Gln Phe Val Glu Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val 165 170 175 Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Glu Ala 180 185 190 Gly Val Gln Ala Val Gly Val Gly Glu Ala Leu Asn Glu Gly Thr Pro 195 200 205 Val Glu Val Ala Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Glu Gly 210 215 220 Ala Thr Glu 225 <210> 122 <211> 205 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <220> <221> MISC_FEATURE <222> (2)..(2) <223> X is absent or an amino acid linker <400> 122 Xaa Xaa Met Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala Val Leu 1 5 10 15 Arg Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe 20 25 30 Leu Gly Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala 35 40 45 Asp Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile 50 55 60 Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val 65 70 75 80 Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile 85 90 95 Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met 100 105 110 Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu 115 120 125 Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala Met 130 135 140 Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn 145 150 155 160 Leu Asp Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly 165 170 175 Val Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys 180 185 190 Ala Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu 195 200 205 <210> 123 <211> 238 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <220> <221> MISC_FEATURE <222> (228)..(238) <223> optionally absent <400> 123 Xaa Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala 1 5 10 15 Ala Lys Ala Glu Glu Ala Ala Arg Met Glu Glu Leu Phe Lys Glu His 20 25 30 Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Lys Lys 35 40 45 Lys Ala Leu Ala Val Phe Leu Gly Gly Val Asp Leu Ile Glu Ile Thr 50 55 60 Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Glu Leu Ser Phe Leu 65 70 75 80 Lys Glu Met Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu 85 90 95 Gln Ala Arg Glu Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro 100 105 110 His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Glu Gly Val Phe 115 120 125 Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys 130 135 140 Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro 145 150 155 160 Gln Phe Val Glu Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val 165 170 175 Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Glu Ala 180 185 190 Gly Val Gln Ala Val Gly Val Gly Glu Ala Leu Asn Glu Gly Thr Pro 195 200 205 Val Glu Val Ala Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Glu Gly 210 215 220 Ala Thr Glu Gly Gly Ser His His His His His His His His 225 230 235 <210> 124 <211> 216 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> X is at least one second protein comprises an immunogenic portion of a SARS-CoV-2 antigen or a variant or homolog thereof <220> <221> MISC_FEATURE <222> (2)..(2) <223> X is absent or an amino acid linker <220> <221> MISC_FEATURE <222> (206)..(216) <223> optionally absent <400> 124 Xaa Xaa Met Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala Val Leu 1 5 10 15 Arg Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe 20 25 30 Leu Gly Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala 35 40 45 Asp Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile 50 55 60 Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val 65 70 75 80 Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile 85 90 95 Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met 100 105 110 Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu 115 120 125 Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala Met 130 135 140 Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn 145 150 155 160 Leu Asp Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly 165 170 175 Val Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys 180 185 190 Ala Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu Gly Gly Ser 195 200 205 His His His His His His His His 210 215 <210> 125 <211> 204 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 125 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 1 5 10 15 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 20 25 30 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 35 40 45 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 50 55 60 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 65 70 75 80 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 85 90 95 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 100 105 110 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 115 120 125 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 130 135 140 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 145 150 155 160 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 165 170 175 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 180 185 190 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 195 200 <210> 126 <211> 208 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 126 Glu Thr Gly Thr Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 1 5 10 15 Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 20 25 30 Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 35 40 45 Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 50 55 60 Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg 65 70 75 80 Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala 85 90 95 Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 100 105 110 Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 115 120 125 Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 130 135 140 Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 145 150 155 160 Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 165 170 175 Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 180 185 190 Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 195 200 205 <210> 127 <211> 1198 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 127 Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr 1 5 10 15 Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser 20 25 30 Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn 35 40 45 Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys 50 55 60 Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala 65 70 75 80 Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr 85 90 95 Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn 100 105 110 Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln 145 150 155 160 Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu 165 170 175 Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser 180 185 190 Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser 195 200 205 Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg 210 215 220 Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp 225 230 235 240 Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr 245 250 255 Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile 260 265 270 Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 275 280 285 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 290 295 300 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 305 310 315 320 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 325 330 335 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 340 345 350 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 355 360 365 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 370 375 380 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 385 390 395 400 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 405 410 415 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 420 425 430 Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu 435 440 445 Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser 450 455 460 Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln 465 470 475 480 Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys 530 535 540 Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Ser Gly Ala Gly 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys 1190 1195 <210> 128 <211> 1202 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(4) <223> optionally absent <400> 128 Glu Thr Gly Thr Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro 1 5 10 15 Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys 20 25 30 Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro 35 40 45 Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr 50 55 60 Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly 65 70 75 80 Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile 85 90 95 Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn 100 105 110 Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn 115 120 125 Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met 130 135 140 Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu 145 150 155 160 Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn 165 170 175 Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe 180 185 190 Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro 195 200 205 Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile 210 215 220 Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu 225 230 235 240 Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr 245 250 255 Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu 260 265 270 Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser 275 280 285 Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr 290 295 300 Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe 305 310 315 320 Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr 325 330 335 Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys 340 345 350 Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe 355 360 365 Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr 370 375 380 Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln 385 390 395 400 Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu 405 410 415 Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu 420 425 430 Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg 435 440 445 Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr 450 455 460 Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr 465 470 475 480 Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr 485 490 495 Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro 500 505 510 Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys 515 520 525 Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr 530 535 540 Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile 545 550 555 560 Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu 565 570 575 Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly 580 585 590 Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys 595 600 605 Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp 610 615 620 Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys 625 630 635 640 Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro 645 650 655 Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro 660 665 670 Ser Gly Ala Gly Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met 675 680 685 Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala 690 695 700 Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val 705 710 715 720 Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp 725 730 735 Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr 740 745 750 Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn 755 760 765 Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro 770 775 780 Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro 785 790 795 800 Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys 805 810 815 Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu 820 825 830 Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly 835 840 845 Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr 850 855 860 Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly 865 870 875 880 Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg 885 890 895 Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys 900 905 910 Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser 915 920 925 Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn 930 935 940 Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn 945 950 955 960 Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp 965 970 975 Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu 980 985 990 Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu 995 1000 1005 Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys 1010 1015 1020 Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr 1025 1030 1035 His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe 1040 1045 1050 Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr 1055 1060 1065 Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu 1070 1075 1080 Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg 1085 1090 1095 Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val 1100 1105 1110 Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val 1115 1120 1125 Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu 1130 1135 1140 Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly 1145 1150 1155 Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu 1160 1165 1170 Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu 1175 1180 1185 Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys 1190 1195 1200 <210> 129 <211> 1230 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 129 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr 35 40 45 Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser 50 55 60 Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn 65 70 75 80 Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys 85 90 95 Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala 100 105 110 Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr 115 120 125 Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn 130 135 140 Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu 145 150 155 160 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 165 170 175 Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln 180 185 190 Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu 195 200 205 Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser 210 215 220 Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser 225 230 235 240 Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg 245 250 255 Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp 260 265 270 Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr 275 280 285 Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile 290 295 300 Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 305 310 315 320 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 325 330 335 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 340 345 350 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 355 360 365 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 370 375 380 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 385 390 395 400 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 405 410 415 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 420 425 430 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 435 440 445 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 450 455 460 Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu 465 470 475 480 Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser 485 490 495 Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln 500 505 510 Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg 515 520 525 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 530 535 540 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 545 550 555 560 Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys 565 570 575 Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr 580 585 590 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 595 600 605 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 610 615 620 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 625 630 635 640 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 645 650 655 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 660 665 670 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 675 680 685 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Ser Gly Ala Gly 690 695 700 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 705 710 715 720 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 725 730 735 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 740 745 750 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 755 760 765 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 770 775 780 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 785 790 795 800 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 805 810 815 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 820 825 830 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 835 840 845 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 850 855 860 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 865 870 875 880 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 885 890 895 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 900 905 910 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 915 920 925 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 930 935 940 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 945 950 955 960 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 965 970 975 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 980 985 990 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 995 1000 1005 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu 1010 1015 1020 Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg 1025 1030 1035 Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu 1040 1045 1050 Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu 1055 1060 1065 Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His 1070 1075 1080 Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro 1085 1090 1095 Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val 1100 1105 1110 Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe 1115 1120 1125 Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly 1130 1135 1140 Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp 1145 1150 1155 Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys 1160 1165 1170 Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile 1175 1180 1185 Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp 1190 1195 1200 Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp 1205 1210 1215 Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys 1220 1225 1230 <210> 130 <211> 1208 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(15) <223> optionally absent <400> 130 Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gly Ser Ala Ser Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Pro Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Pro Ala Leu Gln Ile 885 890 895 Pro Phe Pro Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Pro Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln 1205 <210> 131 <211> 1160 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(15) <223> optionally absent <400> 131 Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gly Ser Ala Ser Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Pro Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Pro Ala Leu Gln Ile 885 890 895 Pro Phe Pro Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Pro Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr 1160 <210> 132 <211> 1195 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(2) <223> optionally absent <400> 132 Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr 1 5 10 15 Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser 20 25 30 Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn 35 40 45 Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys 50 55 60 Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala 65 70 75 80 Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr 85 90 95 Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn 100 105 110 Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln 145 150 155 160 Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu 165 170 175 Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser 180 185 190 Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser 195 200 205 Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg 210 215 220 Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp 225 230 235 240 Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr 245 250 255 Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile 260 265 270 Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 275 280 285 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 290 295 300 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 305 310 315 320 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 325 330 335 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 340 345 350 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 355 360 365 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 370 375 380 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 385 390 395 400 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 405 410 415 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 420 425 430 Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu 435 440 445 Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser 450 455 460 Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln 465 470 475 480 Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys 530 535 540 Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gly Ser Ala Ser 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Pro Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Pro Ala 865 870 875 880 Leu Gln Ile Pro Phe Pro Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Pro Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln 1190 1195 <210> 133 <211> 1147 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(2) <223> optionally absent <400> 133 Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr 1 5 10 15 Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser 20 25 30 Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn 35 40 45 Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys 50 55 60 Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala 65 70 75 80 Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr 85 90 95 Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn 100 105 110 Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln 145 150 155 160 Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu 165 170 175 Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser 180 185 190 Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser 195 200 205 Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg 210 215 220 Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp 225 230 235 240 Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr 245 250 255 Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile 260 265 270 Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 275 280 285 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 290 295 300 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 305 310 315 320 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 325 330 335 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 340 345 350 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 355 360 365 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 370 375 380 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 385 390 395 400 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 405 410 415 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 420 425 430 Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu 435 440 445 Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser 450 455 460 Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln 465 470 475 480 Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys 530 535 540 Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gly Ser Ala Ser 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Pro Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Pro Ala 865 870 875 880 Leu Gln Ile Pro Phe Pro Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Pro Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr 1145 <210> 134 <211> 1193 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 134 Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser 1 5 10 15 Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val 20 25 30 Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr 35 40 45 Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe 50 55 60 Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr 65 70 75 80 Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp 85 90 95 Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val 100 105 110 Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val 115 120 125 Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val 130 135 140 Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe 145 150 155 160 Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu 165 170 175 Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His 180 185 190 Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu 195 200 205 Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln 210 215 220 Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser 225 230 235 240 Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln 245 250 255 Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp 260 265 270 Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu 275 280 285 Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg 290 295 300 Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu 305 310 315 320 Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr 325 330 335 Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val 340 345 350 Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser 355 360 365 Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser 370 375 380 Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr 385 390 395 400 Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly 405 410 415 Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly 420 425 430 Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro 435 440 445 Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro 450 455 460 Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr 465 470 475 480 Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val 485 490 495 Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro 500 505 510 Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe 515 520 525 Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe 530 535 540 Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala 545 550 555 560 Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser 565 570 575 Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln 580 585 590 Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala 595 600 605 Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly 610 615 620 Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His 625 630 635 640 Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys 645 650 655 Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gly Ser Ala Ser Ser Val 660 665 670 Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn 675 680 685 Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr 690 695 700 Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser 705 710 715 720 Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn 725 730 735 Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu 740 745 750 Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala 755 760 765 Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly 770 775 780 Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg 785 790 795 800 Ser Pro Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala 805 810 815 Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg 820 825 830 Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro 835 840 845 Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala 850 855 860 Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Pro Ala Leu Gln 865 870 875 880 Ile Pro Phe Pro Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val 885 890 895 Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe 900 905 910 Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Pro Ser 915 920 925 Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu 930 935 940 Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser 945 950 955 960 Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val 965 970 975 Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr 980 985 990 Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 995 1000 1005 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1010 1015 1020 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1025 1030 1035 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1040 1045 1050 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1055 1060 1065 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1070 1075 1080 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1085 1090 1095 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1100 1105 1110 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1115 1120 1125 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1130 1135 1140 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1145 1150 1155 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1160 1165 1170 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1175 1180 1185 Gly Lys Tyr Glu Gln 1190 <210> 135 <211> 1145 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 135 Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser 1 5 10 15 Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val 20 25 30 Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr 35 40 45 Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe 50 55 60 Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr 65 70 75 80 Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp 85 90 95 Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val 100 105 110 Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val 115 120 125 Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val 130 135 140 Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe 145 150 155 160 Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu 165 170 175 Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His 180 185 190 Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu 195 200 205 Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln 210 215 220 Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser 225 230 235 240 Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln 245 250 255 Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp 260 265 270 Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu 275 280 285 Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg 290 295 300 Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu 305 310 315 320 Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr 325 330 335 Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val 340 345 350 Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser 355 360 365 Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser 370 375 380 Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr 385 390 395 400 Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly 405 410 415 Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly 420 425 430 Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro 435 440 445 Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro 450 455 460 Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr 465 470 475 480 Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val 485 490 495 Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro 500 505 510 Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe 515 520 525 Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe 530 535 540 Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala 545 550 555 560 Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser 565 570 575 Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln 580 585 590 Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala 595 600 605 Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly 610 615 620 Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His 625 630 635 640 Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys 645 650 655 Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gly Ser Ala Ser Ser Val 660 665 670 Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn 675 680 685 Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr 690 695 700 Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser 705 710 715 720 Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn 725 730 735 Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu 740 745 750 Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala 755 760 765 Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly 770 775 780 Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg 785 790 795 800 Ser Pro Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala 805 810 815 Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg 820 825 830 Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro 835 840 845 Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala 850 855 860 Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Pro Ala Leu Gln 865 870 875 880 Ile Pro Phe Pro Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val 885 890 895 Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe 900 905 910 Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Pro Ser 915 920 925 Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu 930 935 940 Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser 945 950 955 960 Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val 965 970 975 Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr 980 985 990 Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 995 1000 1005 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1010 1015 1020 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1025 1030 1035 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1040 1045 1050 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1055 1060 1065 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1070 1075 1080 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1085 1090 1095 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1100 1105 1110 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1115 1120 1125 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1130 1135 1140 His Thr 1145 <210> 136 <211> 1199 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 136 Glu Thr Cys Thr Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro 1 5 10 15 Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys 20 25 30 Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro 35 40 45 Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr 50 55 60 Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly 65 70 75 80 Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile 85 90 95 Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn 100 105 110 Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn 115 120 125 Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met 130 135 140 Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu 145 150 155 160 Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn 165 170 175 Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe 180 185 190 Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro 195 200 205 Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile 210 215 220 Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu 225 230 235 240 Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr 245 250 255 Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu 260 265 270 Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser 275 280 285 Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr 290 295 300 Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe 305 310 315 320 Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr 325 330 335 Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys 340 345 350 Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe 355 360 365 Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr 370 375 380 Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln 385 390 395 400 Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu 405 410 415 Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu 420 425 430 Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg 435 440 445 Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr 450 455 460 Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr 465 470 475 480 Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr 485 490 495 Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro 500 505 510 Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys 515 520 525 Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr 530 535 540 Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile 545 550 555 560 Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu 565 570 575 Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly 580 585 590 Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys 595 600 605 Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp 610 615 620 Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys 625 630 635 640 Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro 645 650 655 Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro 660 665 670 Gly Ser Ala Ser Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met 675 680 685 Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala 690 695 700 Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val 705 710 715 720 Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp 725 730 735 Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr 740 745 750 Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn 755 760 765 Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro 770 775 780 Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro 785 790 795 800 Ser Lys Pro Ser Lys Arg Ser Pro Ile Glu Asp Leu Leu Phe Asn Lys 805 810 815 Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu 820 825 830 Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly 835 840 845 Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr 850 855 860 Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly 865 870 875 880 Ala Gly Pro Ala Leu Gln Ile Pro Phe Pro Met Gln Met Ala Tyr Arg 885 890 895 Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys 900 905 910 Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser 915 920 925 Leu Ser Ser Thr Pro Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn 930 935 940 Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn 945 950 955 960 Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp 965 970 975 Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu 980 985 990 Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu 995 1000 1005 Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys 1010 1015 1020 Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr 1025 1030 1035 His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe 1040 1045 1050 Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr 1055 1060 1065 Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu 1070 1075 1080 Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg 1085 1090 1095 Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val 1100 1105 1110 Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val 1115 1120 1125 Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu 1130 1135 1140 Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly 1145 1150 1155 Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu 1160 1165 1170 Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu 1175 1180 1185 Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln 1190 1195 <210> 137 <211> 1151 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 137 Glu Thr Cys Thr Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro 1 5 10 15 Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys 20 25 30 Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro 35 40 45 Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr 50 55 60 Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly 65 70 75 80 Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile 85 90 95 Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn 100 105 110 Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn 115 120 125 Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met 130 135 140 Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu 145 150 155 160 Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn 165 170 175 Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe 180 185 190 Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro 195 200 205 Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile 210 215 220 Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu 225 230 235 240 Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr 245 250 255 Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu 260 265 270 Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser 275 280 285 Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr 290 295 300 Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe 305 310 315 320 Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr 325 330 335 Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys 340 345 350 Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe 355 360 365 Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr 370 375 380 Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln 385 390 395 400 Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu 405 410 415 Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu 420 425 430 Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg 435 440 445 Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr 450 455 460 Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr 465 470 475 480 Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr 485 490 495 Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro 500 505 510 Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys 515 520 525 Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr 530 535 540 Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile 545 550 555 560 Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu 565 570 575 Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly 580 585 590 Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys 595 600 605 Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp 610 615 620 Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys 625 630 635 640 Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro 645 650 655 Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro 660 665 670 Gly Ser Ala Ser Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met 675 680 685 Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala 690 695 700 Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val 705 710 715 720 Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp 725 730 735 Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr 740 745 750 Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn 755 760 765 Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro 770 775 780 Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro 785 790 795 800 Ser Lys Pro Ser Lys Arg Ser Pro Ile Glu Asp Leu Leu Phe Asn Lys 805 810 815 Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu 820 825 830 Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly 835 840 845 Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr 850 855 860 Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly 865 870 875 880 Ala Gly Pro Ala Leu Gln Ile Pro Phe Pro Met Gln Met Ala Tyr Arg 885 890 895 Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys 900 905 910 Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser 915 920 925 Leu Ser Ser Thr Pro Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn 930 935 940 Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn 945 950 955 960 Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp 965 970 975 Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu 980 985 990 Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu 995 1000 1005 Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys 1010 1015 1020 Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr 1025 1030 1035 His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe 1040 1045 1050 Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr 1055 1060 1065 Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu 1070 1075 1080 Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg 1085 1090 1095 Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val 1100 1105 1110 Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val 1115 1120 1125 Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu 1130 1135 1140 Asp Lys Tyr Phe Lys Asn His Thr 1145 1150 <210> 138 <211> 1446 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(15) <223> optionally absent <220> <221> MISC_FEATURE <222> (1209)..(1231) <223> optionally absent <220> <221> MISC_FEATURE <222> (1436)..(1446) <223> optionally absent <400> 138 Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gly Ser Ala Ser Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Pro Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Pro Ala Leu Gln Ile 885 890 895 Pro Phe Pro Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Pro Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser 1205 1210 1215 Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu Ala Ala Arg Lys Met 1220 1225 1230 Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala 1235 1240 1245 Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala 1250 1255 1260 Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala 1265 1270 1275 Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala 1280 1285 1290 Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys 1295 1300 1305 Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp 1310 1315 1320 Glu Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met 1325 1330 1335 Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu 1340 1345 1350 Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro 1355 1360 1365 Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe 1370 1375 1380 Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe 1385 1390 1395 Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys 1400 1405 1410 Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu 1415 1420 1425 Lys Ile Arg Gly Ala Thr Glu Gly Gly Ser His His His His His 1430 1435 1440 His His His 1445 <210> 139 <211> 1475 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(15) <223> optionally absent <220> <221> MISC_FEATURE <222> (1209)..(1260) <223> optionally absent <220> <221> MISC_FEATURE <222> (1465)..(1475) <223> optionally absent <400> 139 Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gly Ser Ala Ser Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Pro Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Pro Ala Leu Gln Ile 885 890 895 Pro Phe Pro Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Pro Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn 1160 1165 1170 Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu 1175 1180 1185 Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu 1190 1195 1200 Gly Lys Tyr Glu Gln Gly Ser Gly Tyr Ile Pro Glu Ala Pro Arg 1205 1210 1215 Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu 1220 1225 1230 Ser Thr Phe Leu Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly 1235 1240 1245 Ser Glu Lys Ala Ala Lys Ala Glu Glu Ala Ala Arg Lys Met Glu 1250 1255 1260 Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn 1265 1270 1275 Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly 1280 1285 1290 Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp 1295 1300 1305 Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile 1310 1315 1320 Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala 1325 1330 1335 Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu 1340 1345 1350 Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro 1355 1360 1365 Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly 1370 1375 1380 His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln 1385 1390 1395 Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val 1400 1405 1410 Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys 1415 1420 1425 Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly 1430 1435 1440 Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys 1445 1450 1455 Ile Arg Gly Ala Thr Glu Gly Gly Ser His His His His His His 1460 1465 1470 His His 1475 <210> 140 <211> 1398 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(15) <223> optionally absent <220> <221> MISC_FEATURE <222> (1161)..(1183) <223> optionally absent <220> <221> MISC_FEATURE <222> (1388)..(1398) <223> optionally absent <400> 140 Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gly Ser Ala Ser Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Pro Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Pro Ala Leu Gln Ile 885 890 895 Pro Phe Pro Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Pro Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu 1160 1165 1170 Lys Ala Ala Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu Leu 1175 1180 1185 Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val 1190 1195 1200 Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val 1205 1210 1215 His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val 1220 1225 1230 Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly 1235 1240 1245 Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala Val Glu 1250 1255 1260 Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile 1265 1270 1275 Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val 1280 1285 1290 Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr 1295 1300 1305 Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val 1310 1315 1320 Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr 1325 1330 1335 Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly 1340 1345 1350 Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro 1355 1360 1365 Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg 1370 1375 1380 Gly Ala Thr Glu Gly Gly Ser His His His His His His His His 1385 1390 1395 <210> 141 <211> 1427 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(15) <223> optionally absent <220> <221> MISC_FEATURE <222> (1161)..(1212) <223> optionally absent <220> <221> MISC_FEATURE <222> (1417)..(1427) <223> optionally absent <400> 141 Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 1 5 10 15 Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 20 25 30 Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 35 40 45 His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 50 55 60 Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 65 70 75 80 Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 85 90 95 Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 100 105 110 Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 115 120 125 Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 130 135 140 Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 145 150 155 160 Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 165 170 175 Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 180 185 190 Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 195 200 205 Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 210 215 220 Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 225 230 235 240 Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 245 250 255 Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 260 265 270 Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 275 280 285 Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 290 295 300 Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 305 310 315 320 Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 325 330 335 Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 340 345 350 Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 355 360 365 Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 370 375 380 Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 385 390 395 400 Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 405 410 415 Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 420 425 430 Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 435 440 445 Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 450 455 460 Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 465 470 475 480 Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 485 490 495 Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 500 505 510 Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 515 520 525 Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 530 535 540 Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 545 550 555 560 Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 565 570 575 Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 580 585 590 Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 595 600 605 Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 610 615 620 His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 625 630 635 640 Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 645 650 655 Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 660 665 670 Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gly Ser Ala Ser Ser Val Ala 675 680 685 Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 690 695 700 Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 705 710 715 720 Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 725 730 735 Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 740 745 750 Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 755 760 765 Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 770 775 780 Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 785 790 795 800 Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 805 810 815 Pro Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 820 825 830 Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 835 840 845 Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 850 855 860 Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 865 870 875 880 Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Pro Ala Leu Gln Ile 885 890 895 Pro Phe Pro Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 900 905 910 Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 915 920 925 Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Pro Ser Ala 930 935 940 Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 945 950 955 960 Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 965 970 975 Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val Gln 980 985 990 Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 995 1000 1005 Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn 1010 1015 1020 Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys 1025 1030 1035 Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 1040 1045 1050 Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val 1055 1060 1065 Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His 1070 1075 1080 Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn 1085 1090 1095 Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln 1100 1105 1110 Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val 1115 1120 1125 Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro 1130 1135 1140 Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn 1145 1150 1155 His Thr Gly Ser Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln 1160 1165 1170 Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe 1175 1180 1185 Leu Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys 1190 1195 1200 Ala Ala Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe 1205 1210 1215 Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu 1220 1225 1230 Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val His 1235 1240 1245 Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile 1250 1255 1260 Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala 1265 1270 1275 Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala Val Glu Ser 1280 1285 1290 Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser 1295 1300 1305 Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met 1310 1315 1320 Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile 1325 1330 1335 Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys 1340 1345 1350 Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly 1355 1360 1365 Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val 1370 1375 1380 Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp 1385 1390 1395 Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly 1400 1405 1410 Ala Thr Glu Gly Gly Ser His His His His His His His His 1415 1420 1425 <210> 142 <211> 478 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (237)..(263) <223> optionally absent <220> <221> MISC_FEATURE <222> (468)..(478) <223> optionally absent <400> 142 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 35 40 45 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 50 55 60 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 65 70 75 80 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 85 90 95 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 100 105 110 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 115 120 125 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 130 135 140 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 145 150 155 160 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 165 170 175 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 180 185 190 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Tyr Gly Val 195 200 205 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 210 215 220 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Gly Gly Ser Gly 225 230 235 240 Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala 245 250 255 Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His 260 265 270 Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu 275 280 285 Lys Ala Val Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr 290 295 300 Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu 305 310 315 320 Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu 325 330 335 Gln Ala Arg Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro 340 345 350 His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe 355 360 365 Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys 370 375 380 Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro 385 390 395 400 Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val 405 410 415 Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala 420 425 430 Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro 435 440 445 Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly 450 455 460 Ala Thr Glu Gly Gly Ser His His His His His His His His 465 470 475 <210> 143 <211> 478 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (237)..(263) <223> optionally absent <220> <221> MISC_FEATURE <222> (468)..(478) <223> optionally absent <400> 143 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 35 40 45 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 50 55 60 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 65 70 75 80 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 85 90 95 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 100 105 110 Arg Gln Ile Ala Pro Gly Gln Thr Gly Asn Ile Ala Asp Tyr Asn Tyr 115 120 125 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 130 135 140 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 145 150 155 160 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 165 170 175 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Lys Gly Phe Asn 180 185 190 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Tyr Gly Val 195 200 205 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 210 215 220 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Gly Gly Ser Gly 225 230 235 240 Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala 245 250 255 Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His 260 265 270 Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu 275 280 285 Lys Ala Val Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr 290 295 300 Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu 305 310 315 320 Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu 325 330 335 Gln Ala Arg Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro 340 345 350 His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe 355 360 365 Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys 370 375 380 Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro 385 390 395 400 Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val 405 410 415 Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala 420 425 430 Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro 435 440 445 Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly 450 455 460 Ala Thr Glu Gly Gly Ser His His His His His His His His 465 470 475 <210> 144 <211> 478 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (237)..(263) <223> optionally absent <220> <221> MISC_FEATURE <222> (468)..(478) <223> optionally absent <400> 144 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 35 40 45 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 50 55 60 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 65 70 75 80 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 85 90 95 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 100 105 110 Arg Gln Ile Ala Pro Gly Gln Thr Gly Thr Ile Ala Asp Tyr Asn Tyr 115 120 125 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 130 135 140 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 145 150 155 160 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 165 170 175 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Lys Gly Phe Asn 180 185 190 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Tyr Gly Val 195 200 205 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 210 215 220 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Gly Gly Ser Gly 225 230 235 240 Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala 245 250 255 Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His 260 265 270 Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu 275 280 285 Lys Ala Val Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr 290 295 300 Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu 305 310 315 320 Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu 325 330 335 Gln Ala Arg Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro 340 345 350 His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe 355 360 365 Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys 370 375 380 Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro 385 390 395 400 Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val 405 410 415 Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala 420 425 430 Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro 435 440 445 Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly 450 455 460 Ala Thr Glu Gly Gly Ser His His His His His His His His 465 470 475 <210> 145 <211> 478 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (237)..(263) <223> optionally absent <220> <221> MISC_FEATURE <222> (468)..(478) <223> optionally absent <400> 145 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 35 40 45 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 50 55 60 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 65 70 75 80 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 85 90 95 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 100 105 110 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 115 120 125 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 130 135 140 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 145 150 155 160 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 165 170 175 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Lys Gly Phe Asn 180 185 190 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 195 200 205 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 210 215 220 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Gly Gly Ser Gly 225 230 235 240 Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala 245 250 255 Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His 260 265 270 Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu 275 280 285 Lys Ala Val Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr 290 295 300 Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu 305 310 315 320 Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu 325 330 335 Gln Ala Arg Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro 340 345 350 His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe 355 360 365 Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys 370 375 380 Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro 385 390 395 400 Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val 405 410 415 Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala 420 425 430 Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro 435 440 445 Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly 450 455 460 Ala Thr Glu Gly Gly Ser His His His His His His His His 465 470 475 <210> 146 <211> 478 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (237)..(263) <223> optionally absent <220> <221> MISC_FEATURE <222> (468)..(478) <223> optionally absent <400> 146 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 35 40 45 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 50 55 60 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 65 70 75 80 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 85 90 95 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 100 105 110 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 115 120 125 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 130 135 140 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Arg Tyr Arg Leu 145 150 155 160 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 165 170 175 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 180 185 190 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 195 200 205 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 210 215 220 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Gly Gly Ser Gly 225 230 235 240 Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala 245 250 255 Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His 260 265 270 Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu 275 280 285 Lys Ala Val Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr 290 295 300 Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu 305 310 315 320 Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu 325 330 335 Gln Ala Arg Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro 340 345 350 His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe 355 360 365 Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys 370 375 380 Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro 385 390 395 400 Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val 405 410 415 Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala 420 425 430 Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro 435 440 445 Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly 450 455 460 Ala Thr Glu Gly Gly Ser His His His His His His His His 465 470 475 <210> 147 <211> 474 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(28) <223> optionally absent <220> <221> MISC_FEATURE <222> (233)..(259) <223> optionally absent <220> <221> MISC_FEATURE <222> (464)..(474) <223> optionally absent <400> 147 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Arg Phe Pro Asn 20 25 30 Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe 35 40 45 Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala 50 55 60 Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys 65 70 75 80 Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val 85 90 95 Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala 100 105 110 Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp 115 120 125 Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser 130 135 140 Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser 145 150 155 160 Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala 165 170 175 Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro 180 185 190 Leu Gln Ser Tyr Gly Phe Gln Pro Thr Tyr Gly Val Gly Tyr Gln Pro 195 200 205 Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr 210 215 220 Val Cys Gly Pro Lys Lys Ser Thr Gly Gly Ser Gly Gly Ser Gly Ser 225 230 235 240 Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu 245 250 255 Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala 260 265 270 Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala 275 280 285 Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro 290 295 300 Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly 305 310 315 320 Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys 325 330 335 Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu 340 345 350 Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly 355 360 365 Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr 370 375 380 Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys 385 390 395 400 Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly 405 410 415 Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala 420 425 430 Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg 435 440 445 Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu Gly 450 455 460 Gly Ser His His His His His His His His 465 470 <210> 148 <211> 474 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(28) <223> optionally absent <220> <221> MISC_FEATURE <222> (233)..(259) <223> optionally absent <220> <221> MISC_FEATURE <222> (464)..(474) <223> optionally absent <400> 148 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Arg Phe Pro Asn 20 25 30 Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe 35 40 45 Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala 50 55 60 Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys 65 70 75 80 Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val 85 90 95 Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala 100 105 110 Pro Gly Gln Thr Gly Asn Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp 115 120 125 Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser 130 135 140 Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser 145 150 155 160 Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala 165 170 175 Gly Ser Thr Pro Cys Asn Gly Val Lys Gly Phe Asn Cys Tyr Phe Pro 180 185 190 Leu Gln Ser Tyr Gly Phe Gln Pro Thr Tyr Gly Val Gly Tyr Gln Pro 195 200 205 Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr 210 215 220 Val Cys Gly Pro Lys Lys Ser Thr Gly Gly Ser Gly Gly Ser Gly Ser 225 230 235 240 Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu 245 250 255 Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala 260 265 270 Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala 275 280 285 Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro 290 295 300 Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly 305 310 315 320 Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys 325 330 335 Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu 340 345 350 Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly 355 360 365 Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr 370 375 380 Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys 385 390 395 400 Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly 405 410 415 Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala 420 425 430 Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg 435 440 445 Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu Gly 450 455 460 Gly Ser His His His His His His His His 465 470 <210> 149 <211> 474 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(18) <223> optionally absent <220> <221> MISC_FEATURE <222> (233)..(259) <223> optionally absent <220> <221> MISC_FEATURE <222> (464)..(474) <223> optionally absent <400> 149 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Arg Phe Pro Asn 20 25 30 Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe 35 40 45 Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala 50 55 60 Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys 65 70 75 80 Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val 85 90 95 Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala 100 105 110 Pro Gly Gln Thr Gly Thr Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp 115 120 125 Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser 130 135 140 Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser 145 150 155 160 Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala 165 170 175 Gly Ser Thr Pro Cys Asn Gly Val Lys Gly Phe Asn Cys Tyr Phe Pro 180 185 190 Leu Gln Ser Tyr Gly Phe Gln Pro Thr Tyr Gly Val Gly Tyr Gln Pro 195 200 205 Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr 210 215 220 Val Cys Gly Pro Lys Lys Ser Thr Gly Gly Ser Gly Gly Ser Gly Ser 225 230 235 240 Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu 245 250 255 Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala 260 265 270 Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala 275 280 285 Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro 290 295 300 Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly 305 310 315 320 Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys 325 330 335 Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu 340 345 350 Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly 355 360 365 Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr 370 375 380 Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys 385 390 395 400 Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly 405 410 415 Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala 420 425 430 Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg 435 440 445 Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu Gly 450 455 460 Gly Ser His His His His His His His His 465 470 <210> 150 <211> 474 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(28) <223> optionally absent <220> <221> MISC_FEATURE <222> (233)..(259) <223> optionally absent <220> <221> MISC_FEATURE <222> (464)..(474) <223> optionally absent <400> 150 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Arg Phe Pro Asn 20 25 30 Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe 35 40 45 Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala 50 55 60 Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys 65 70 75 80 Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val 85 90 95 Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala 100 105 110 Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp 115 120 125 Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser 130 135 140 Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser 145 150 155 160 Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala 165 170 175 Gly Ser Thr Pro Cys Asn Gly Val Lys Gly Phe Asn Cys Tyr Phe Pro 180 185 190 Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro 195 200 205 Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr 210 215 220 Val Cys Gly Pro Lys Lys Ser Thr Gly Gly Ser Gly Gly Ser Gly Ser 225 230 235 240 Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu 245 250 255 Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala 260 265 270 Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala 275 280 285 Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro 290 295 300 Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly 305 310 315 320 Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys 325 330 335 Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu 340 345 350 Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly 355 360 365 Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr 370 375 380 Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys 385 390 395 400 Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly 405 410 415 Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala 420 425 430 Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg 435 440 445 Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu Gly 450 455 460 Gly Ser His His His His His His His His 465 470 <210> 151 <211> 474 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(28) <223> optionally absent <220> <221> MISC_FEATURE <222> (233)..(259) <223> optionally absent <220> <221> MISC_FEATURE <222> (464)..(474) <223> optionally absent <400> 151 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Arg Phe Pro Asn 20 25 30 Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe 35 40 45 Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala 50 55 60 Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys 65 70 75 80 Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val 85 90 95 Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala 100 105 110 Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp 115 120 125 Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser 130 135 140 Lys Val Gly Gly Asn Tyr Asn Tyr Arg Tyr Arg Leu Phe Arg Lys Ser 145 150 155 160 Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala 165 170 175 Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro 180 185 190 Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro 195 200 205 Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr 210 215 220 Val Cys Gly Pro Lys Lys Ser Thr Gly Gly Ser Gly Gly Ser Gly Ser 225 230 235 240 Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu 245 250 255 Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala 260 265 270 Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala 275 280 285 Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro 290 295 300 Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly 305 310 315 320 Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys 325 330 335 Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu 340 345 350 Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly 355 360 365 Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr 370 375 380 Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys 385 390 395 400 Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly 405 410 415 Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala 420 425 430 Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg 435 440 445 Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu Gly 450 455 460 Gly Ser His His His His His His His His 465 470 <210> 152 <211> 157 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> optionally absent <400> 152 Met Asn Gln His Ser His Lys Asp Tyr Glu Thr Val Arg Ile Ala Val 1 5 10 15 Val Arg Ala Arg Trp His Ala Glu Ile Val Asp Ala Cys Val Ser Ala 20 25 30 Phe Glu Ala Ala Met Ala Asp Ile Gly Gly Asp Arg Phe Ala Val Asp 35 40 45 Val Phe Asp Val Pro Gly Ala Tyr Glu Ile Pro Leu His Ala Arg Thr 50 55 60 Leu Ala Glu Thr Gly Arg Tyr Gly Ala Val Leu Gly Thr Ala Phe Val 65 70 75 80 Val Asn Gly Gly Ile Tyr Arg His Glu Phe Val Ala Ser Ala Val Ile 85 90 95 Asp Gly Met Met Asn Val Gln Leu Ser Thr Gly Val Pro Val Leu Ser 100 105 110 Ala Val Leu Thr Pro His Arg Tyr Arg Asp Ser Asp Ala His Thr Leu 115 120 125 Leu Phe Leu Ala Leu Phe Ala Val Lys Gly Met Glu Ala Ala Arg Ala 130 135 140 Cys Val Glu Ile Leu Ala Ala Arg Glu Lys Ile Ala Ala 145 150 155 <210> 153 <211> 157 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> optionally absent <400> 153 Met Asn Gln His Ser His Lys Asp His Glu Thr Val Arg Ile Ala Val 1 5 10 15 Val Arg Ala Arg Trp His Ala Glu Ile Val Asp Ala Cys Val Ser Ala 20 25 30 Phe Glu Ala Ala Met Arg Asp Ile Gly Gly Asp Arg Phe Ala Val Asp 35 40 45 Val Phe Asp Val Pro Gly Ala Tyr Glu Ile Pro Leu His Ala Arg Thr 50 55 60 Leu Ala Glu Thr Gly Arg Tyr Gly Ala Val Leu Gly Thr Ala Phe Val 65 70 75 80 Val Asn Gly Gly Ile Tyr Arg His Glu Phe Val Ala Ser Ala Val Ile 85 90 95 Asp Gly Met Met Asn Val Gln Leu Asp Thr Gly Val Pro Val Leu Ser 100 105 110 Ala Val Leu Thr Pro His Arg Tyr Arg Asp Ser Asp Ala His Thr Leu 115 120 125 Leu Phe Leu Ala Leu Phe Ala Val Lys Gly Met Glu Ala Ala Arg Ala 130 135 140 Cys Val Glu Ile Leu Ala Ala Arg Glu Lys Ile Ala Ala 145 150 155 <210> 154 <211> 157 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> optionally absent <400> 154 Met Asn Gln His Ser His Lys Asp His Glu Thr Val Arg Ile Ala Val 1 5 10 15 Val Arg Ala Arg Trp His Ala Glu Ile Val Asp Ala Cys Val Ser Ala 20 25 30 Phe Glu Ala Ala Met Arg Asp Ile Gly Gly Asp Arg Phe Ala Val Asp 35 40 45 Val Phe Asp Val Pro Gly Ala Tyr Glu Ile Pro Leu His Ala Arg Thr 50 55 60 Leu Ala Glu Thr Gly Arg Tyr Gly Ala Val Leu Gly Thr Ala Phe Val 65 70 75 80 Val Asp Gly Gly Ile Tyr Asp His Glu Phe Val Ala Ser Ala Val Ile 85 90 95 Asp Gly Met Met Asn Val Gln Leu Asp Thr Gly Val Pro Val Leu Ser 100 105 110 Ala Val Leu Thr Pro His Glu Tyr Glu Asp Ser Asp Ala Asp Thr Leu 115 120 125 Leu Phe Leu Ala Leu Phe Ala Val Lys Gly Met Glu Ala Ala Arg Ala 130 135 140 Cys Val Glu Ile Leu Ala Ala Arg Glu Lys Ile Ala Ala 145 150 155 <210> 155 <211> 157 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> optionally absent <400> 155 Met Asn Gln His Ser His Lys Asp His Glu Thr Val Arg Ile Ala Val 1 5 10 15 Val Arg Ala Arg Trp His Ala Glu Ile Val Asp Ala Cys Val Ser Ala 20 25 30 Phe Glu Ala Ala Met Arg Asp Ile Gly Gly Asp Arg Phe Ala Val Asp 35 40 45 Val Phe Asp Val Pro Gly Ala Tyr Glu Ile Pro Leu His Ala Arg Thr 50 55 60 Leu Ala Glu Thr Gly Arg Tyr Gly Ala Val Leu Gly Thr Ala Phe Val 65 70 75 80 Val Asn Gly Gly Ile Tyr Arg His Glu Phe Val Ala Ser Ala Val Ile 85 90 95 Asn Gly Met Met Asn Val Gln Leu Asn Thr Gly Val Pro Val Leu Ser 100 105 110 Ala Val Leu Thr Pro His Asn Tyr Asp Lys Ser Lys Ala His Thr Leu 115 120 125 Leu Phe Leu Ala Leu Phe Ala Val Lys Gly Met Glu Ala Ala Arg Ala 130 135 140 Cys Val Glu Ile Leu Ala Ala Arg Glu Lys Ile Ala Ala 145 150 155 <210> 156 <211> 193 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(31) <223> optionally absent <220> <221> MISC_FEATURE <222> (188)..(193) <223> optionally absent <400> 156 Met Gly Ser Ser His His His His His His Ser Ser Gly Leu Val Pro 1 5 10 15 Arg Gly Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Gly Ser Asn 20 25 30 Gln His Ser Gln Lys Asp Gln Glu Thr Val Arg Ile Ala Val Val Arg 35 40 45 Ala Arg Trp His Ala Phe Ile Val Asp Ala Cys Val Ser Ala Phe Glu 50 55 60 Ala Ala Met Arg Lys Ile Gly Gly Glu Arg Phe Ala Val Asp Val Phe 65 70 75 80 Asp Val Pro Gly Ala Tyr Glu Ile Pro Leu His Ala Arg Thr Leu Ala 85 90 95 Lys Thr Gly Arg Tyr Gly Ala Val Leu Gly Thr Ala Phe Val Val Asn 100 105 110 Gly Gly Ile Tyr Arg His Glu Phe Val Ala Ser Ala Val Ile Asp Gly 115 120 125 Met Met Asn Val Gln Leu Asp Thr Gly Val Pro Val Leu Ser Ala Val 130 135 140 Leu Thr Pro His Asn Tyr Asp Lys Ser Asn Ala Lys Thr Leu Leu Phe 145 150 155 160 Leu Ala Leu Phe Ala Val Lys Gly Met Glu Ala Ala Arg Ala Cys Val 165 170 175 Glu Ile Leu Ala Ala Arg Glu Lys Ile Ala Ala Gly Ser Leu Glu Gly 180 185 190 Ser <210> 157 <211> 159 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> optionally absent <220> <221> MISC_FEATURE <222> (158)..(159) <223> optionally absent <400> 157 Met Asn Gln His Ser His Lys Asp His Glu Thr Val Arg Ile Ala Val 1 5 10 15 Val Arg Ala Arg Trp His Ala Glu Ile Val Asp Ala Cys Val Ser Ala 20 25 30 Phe Glu Ala Ala Met Arg Asp Ile Gly Gly Asp Arg Phe Ala Val Asp 35 40 45 Val Phe Asp Val Pro Gly Ala Tyr Glu Ile Pro Leu His Ala Arg Thr 50 55 60 Leu Ala Glu Thr Gly Arg Tyr Gly Ala Val Leu Gly Thr Ala Phe Val 65 70 75 80 Val Asn Gly Gly Ile Tyr Arg His Glu Phe Val Ala Ser Ala Val Ile 85 90 95 Asp Gly Met Met Asn Val Gln Leu Asp Thr Gly Val Pro Val Leu Ser 100 105 110 Ala Val Leu Thr Pro His Asn Tyr Asp Lys Ser Lys Ala His Thr Leu 115 120 125 Leu Phe Leu Ala Leu Phe Ala Val Lys Gly Met Glu Ala Ala Arg Ala 130 135 140 Cys Val Glu Ile Leu Ala Ala Arg Glu Lys Ile Ala Ala Gly Ser 145 150 155 <210> 158 <211> 159 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> optionally absent <220> <221> MISC_FEATURE <222> (158)..(159) <223> optionally absent <400> 158 Met Asn Gln His Ser His Lys Asp His Glu Thr Val Arg Ile Ala Val 1 5 10 15 Val Arg Ala Arg Trp His Ala Phe Ile Val Asp Ala Cys Val Ser Ala 20 25 30 Phe Glu Ala Ala Met Arg Asp Ile Gly Gly Asp Arg Phe Ala Val Asp 35 40 45 Val Phe Asp Val Pro Gly Ala Tyr Glu Ile Pro Leu His Ala Arg Thr 50 55 60 Leu Ala Glu Thr Gly Arg Tyr Gly Ala Val Leu Gly Thr Ala Phe Val 65 70 75 80 Val Asn Gly Gly Ile Tyr Arg His Glu Phe Val Ala Ser Ala Val Ile 85 90 95 Asp Gly Met Met Asn Val Gln Leu Asp Thr Gly Val Pro Val Leu Ser 100 105 110 Ala Val Leu Thr Pro His Asn Tyr Asp Lys Ser Asn Ala Lys Thr Leu 115 120 125 Leu Phe Leu Ala Leu Phe Ala Val Lys Gly Met Glu Ala Ala Arg Ala 130 135 140 Cys Val Glu Ile Leu Ala Ala Arg Glu Lys Ile Ala Ala Gly Ser 145 150 155 <210> 159 <211> 159 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(1) <223> optionally absent <220> <221> MISC_FEATURE <222> (158)..(159) <223> optionally absent <400> 159 Met Asn Gln His Ser His Lys Asp His Glu Thr Val Arg Ile Ala Val 1 5 10 15 Val Arg Ala Arg Trp His Ala Phe Ile Val Asp Ala Cys Val Ser Ala 20 25 30 Phe Glu Ala Ala Met Arg Asp Ile Gly Gly Asp Arg Phe Ala Val Asp 35 40 45 Val Phe Asp Val Pro Gly Ala Tyr Glu Ile Pro Leu His Ala Arg Thr 50 55 60 Leu Ala Glu Thr Gly Arg Tyr Gly Ala Val Leu Gly Thr Ala Phe Val 65 70 75 80 Val Asn Gly Gly Ile Tyr Arg His Glu Phe Val Ala Ser Ala Val Ile 85 90 95 Asp Gly Met Met Asn Val Gln Leu Asp Thr Gly Val Pro Val Leu Ser 100 105 110 Ala Val Leu Thr Pro His Asn Tyr Asp Lys Ser Asn Ala Lys Thr Leu 115 120 125 Leu Phe Leu Ala Leu Phe Ala Val Lys Gly Met Glu Ala Ala Arg Ala 130 135 140 Cys Val Glu Ile Leu Ala Ala Arg Glu Lys Ile Ala Ala Gly Ser 145 150 155 <210> 160 <211> 244 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 160 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 35 40 45 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 50 55 60 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 65 70 75 80 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 85 90 95 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 100 105 110 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 115 120 125 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 130 135 140 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 145 150 155 160 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 165 170 175 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 180 185 190 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 195 200 205 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 210 215 220 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr His His His His 225 230 235 240 His His His His <210> 161 <211> 1281 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 161 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr 35 40 45 Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser 50 55 60 Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn 65 70 75 80 Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys 85 90 95 Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala 100 105 110 Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr 115 120 125 Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn 130 135 140 Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu 145 150 155 160 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 165 170 175 Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln 180 185 190 Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu 195 200 205 Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser 210 215 220 Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser 225 230 235 240 Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg 245 250 255 Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp 260 265 270 Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr 275 280 285 Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile 290 295 300 Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 305 310 315 320 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 325 330 335 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 340 345 350 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 355 360 365 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 370 375 380 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 385 390 395 400 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 405 410 415 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 420 425 430 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 435 440 445 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 450 455 460 Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu 465 470 475 480 Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser 485 490 495 Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln 500 505 510 Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg 515 520 525 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 530 535 540 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 545 550 555 560 Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys 565 570 575 Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr 580 585 590 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 595 600 605 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 610 615 620 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 625 630 635 640 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 645 650 655 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 660 665 670 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 675 680 685 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Ser Gly Ala Gly 690 695 700 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 705 710 715 720 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 725 730 735 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 740 745 750 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 755 760 765 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 770 775 780 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 785 790 795 800 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 805 810 815 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 820 825 830 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 835 840 845 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 850 855 860 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 865 870 875 880 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 885 890 895 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 900 905 910 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 915 920 925 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 930 935 940 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 945 950 955 960 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 965 970 975 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 980 985 990 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 995 1000 1005 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu 1010 1015 1020 Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg 1025 1030 1035 Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu 1040 1045 1050 Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu 1055 1060 1065 Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His 1070 1075 1080 Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro 1085 1090 1095 Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val 1100 1105 1110 Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe 1115 1120 1125 Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly 1130 1135 1140 Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp 1145 1150 1155 Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys 1160 1165 1170 Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile 1175 1180 1185 Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp 1190 1195 1200 Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp 1205 1210 1215 Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Gly Ser Gly 1220 1225 1230 Arg Glu Asn Leu Tyr Phe Gln Gly Gly Gly Gly Ser Gly Tyr Ile 1235 1240 1245 Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly 1250 1255 1260 Glu Trp Val Leu Leu Ser Thr Phe Leu Gly His His His His His 1265 1270 1275 His His His 1280 <210> 162 <211> 860 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 162 Met Ala Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala 1 5 10 15 Leu Ala Ser Thr Ile Glu Glu Gln Ala Lys Thr Phe Leu Asp Lys Phe 20 25 30 Asn His Glu Ala Glu Asp Leu Phe Tyr Gln Ser Ser Leu Ala Ser Trp 35 40 45 Asn Tyr Asn Thr Asn Ile Thr Glu Glu Asn Val Gln Asn Met Asn Asn 50 55 60 Ala Gly Asp Lys Trp Ser Ala Phe Leu Lys Glu Gln Ser Thr Leu Ala 65 70 75 80 Gln Met Tyr Pro Leu Gln Glu Ile Gln Asn Leu Thr Val Lys Leu Gln 85 90 95 Leu Gln Ala Leu Gln Gln Asn Gly Ser Ser Val Leu Ser Glu Asp Lys 100 105 110 Ser Lys Arg Leu Asn Thr Ile Leu Asn Thr Met Ser Thr Ile Tyr Ser 115 120 125 Thr Gly Lys Val Cys Asn Pro Asp Asn Pro Gln Glu Cys Leu Leu Leu 130 135 140 Glu Pro Gly Leu Asn Glu Ile Met Ala Asn Ser Leu Asp Tyr Asn Glu 145 150 155 160 Arg Leu Trp Ala Trp Glu Ser Trp Arg Ser Glu Val Gly Lys Gln Leu 165 170 175 Arg Pro Leu Tyr Glu Glu Tyr Val Val Leu Lys Asn Glu Met Ala Arg 180 185 190 Ala Asn His Tyr Glu Asp Tyr Gly Asp Tyr Trp Arg Gly Asp Tyr Glu 195 200 205 Val Asn Gly Val Asp Gly Tyr Asp Tyr Ser Arg Gly Gln Leu Ile Glu 210 215 220 Asp Val Glu His Thr Phe Glu Glu Ile Lys Pro Leu Tyr Glu His Leu 225 230 235 240 His Ala Tyr Val Arg Ala Lys Leu Met Asn Ala Tyr Pro Ser Tyr Ile 245 250 255 Ser Pro Ile Gly Cys Leu Pro Ala His Leu Leu Gly Asp Met Trp Gly 260 265 270 Arg Phe Trp Thr Asn Leu Tyr Ser Leu Thr Val Pro Phe Gly Gln Lys 275 280 285 Pro Asn Ile Asp Val Thr Asp Ala Met Val Asp Gln Ala Trp Asp Ala 290 295 300 Gln Arg Ile Phe Lys Glu Ala Glu Lys Phe Phe Val Ser Val Gly Leu 305 310 315 320 Pro Asn Met Thr Gln Gly Phe Trp Glu Asn Ser Met Leu Thr Asp Pro 325 330 335 Gly Asn Val Gln Lys Ala Val Cys His Pro Thr Ala Trp Asp Leu Gly 340 345 350 Lys Gly Asp Phe Arg Ile Leu Met Cys Thr Lys Val Thr Met Asp Asp 355 360 365 Phe Leu Thr Ala His His Glu Met Gly His Ile Gln Tyr Asp Met Ala 370 375 380 Tyr Ala Ala Gln Pro Phe Leu Leu Arg Asn Gly Ala Asn Glu Gly Phe 385 390 395 400 His Glu Ala Val Gly Glu Ile Met Ser Leu Ser Ala Ala Thr Pro Lys 405 410 415 His Leu Lys Ser Ile Gly Leu Leu Ser Pro Asp Phe Gln Glu Asp Asn 420 425 430 Glu Thr Glu Ile Asn Phe Leu Leu Lys Gln Ala Leu Thr Ile Val Gly 435 440 445 Thr Leu Pro Phe Thr Tyr Met Leu Glu Lys Trp Arg Trp Met Val Phe 450 455 460 Lys Gly Glu Ile Pro Lys Asp Gln Trp Met Lys Lys Trp Trp Glu Met 465 470 475 480 Lys Arg Glu Ile Val Gly Val Val Glu Pro Val Pro His Asp Glu Thr 485 490 495 Tyr Cys Asp Pro Ala Ser Leu Phe His Val Ser Asn Asp Tyr Ser Phe 500 505 510 Ile Arg Tyr Tyr Thr Gly Thr Leu Tyr Gln Phe Gln Phe Gln Glu Ala 515 520 525 Leu Cys Gln Ala Ala Lys His Glu Gly Pro Leu His Lys Cys Asp Ile 530 535 540 Ser Asn Ser Thr Glu Ala Gly Gln Lys Leu Phe Asn Met Leu Arg Leu 545 550 555 560 Gly Lys Ser Glu Pro Trp Thr Leu Ala Leu Glu Asn Val Val Gly Ala 565 570 575 Lys Asn Met Asn Val Arg Pro Leu Leu Asn Tyr Phe Glu Pro Leu Phe 580 585 590 Thr Trp Leu Lys Asp Gln Asn Lys Asn Ser Phe Val Gly Trp Ser Thr 595 600 605 Asp Trp Ser Pro Tyr Ala Asp Pro Leu Val Pro Arg Gly Ser Gly Gly 610 615 620 Gly Gly Asp Pro Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 625 630 635 640 Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe 645 650 655 Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 660 665 670 Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 675 680 685 Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 690 695 700 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 705 710 715 720 Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 725 730 735 Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 740 745 750 Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 755 760 765 Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 770 775 780 Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 785 790 795 800 Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 805 810 815 Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 820 825 830 Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 835 840 845 Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 850 855 860 <210> 163 <211> 993 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 163 Met Pro Met Gly Ser Leu Gln Pro Leu Ala Thr Leu Tyr Leu Leu Gly 1 5 10 15 Met Leu Val Ala Ser Val Leu Ala Gln Ser Thr Ile Glu Glu Gln Ala 20 25 30 Lys Thr Phe Leu Asp Lys Phe Asn His Glu Ala Glu Asp Leu Phe Tyr 35 40 45 Gln Ser Ser Leu Ala Ser Trp Asn Tyr Asn Thr Asn Ile Thr Glu Glu 50 55 60 Asn Val Gln Asn Met Asn Asn Ala Gly Glu Lys Trp Ser Ala Phe Leu 65 70 75 80 Lys Glu Gln Ser Thr Leu Ala Gln Met Tyr Pro Leu Gln Glu Ile Gln 85 90 95 Asn Leu Thr Val Lys Leu Gln Leu Gln Ala Leu Gln Gln Asn Gly Ser 100 105 110 Ser Val Leu Ser Glu Asp Lys Ser Lys Arg Leu Asn Thr Ile Leu Asn 115 120 125 Thr Met Ser Thr Ile Tyr Ser Thr Gly Lys Val Cys Asn Pro Asn Asn 130 135 140 Pro Gln Glu Cys Leu Leu Leu Asp Pro Gly Leu Asn Glu Ile Met Glu 145 150 155 160 Lys Ser Leu Asp Tyr Asn Glu Arg Leu Trp Ala Trp Glu Gly Trp Arg 165 170 175 Ser Glu Val Gly Lys Gln Leu Arg Pro Leu Tyr Glu Glu Tyr Val Val 180 185 190 Leu Lys Asn Glu Met Ala Arg Ala Asn His Tyr Lys Asp Tyr Gly Asp 195 200 205 Tyr Trp Arg Gly Asn Tyr Glu Val Asn Gly Val Asp Gly Tyr Asp Tyr 210 215 220 Asn Arg Asp Gln Leu Ile Glu Asp Val Glu Arg Thr Phe Glu Glu Ile 225 230 235 240 Lys Pro Leu Tyr Glu His Leu His Ala Tyr Val Arg Ala Lys Leu Met 245 250 255 Asn Ala Tyr Pro Ser Tyr Ile Ser Pro Thr Gly Cys Leu Pro Ala His 260 265 270 Leu Leu Gly Asp Met Trp Gly Arg Phe Trp Thr Asn Leu Tyr Ser Leu 275 280 285 Thr Val Pro Phe Gly Gln Lys Pro Asn Ile Asp Val Thr Asp Ala Met 290 295 300 Val Asn Gln Ala Trp Asn Ala Gln Arg Ile Phe Lys Glu Ala Glu Lys 305 310 315 320 Phe Phe Val Ser Val Gly Leu Pro Asn Met Thr Gln Gly Phe Trp Glu 325 330 335 Asn Ser Met Leu Thr Asp Pro Gly Asn Val Gln Lys Val Val Cys His 340 345 350 Pro Thr Ala Trp Asp Leu Gly Lys Gly Asp Phe Arg Ile Ile Met Cys 355 360 365 Thr Lys Val Thr Met Asp Asp Phe Leu Thr Ala His His Glu Met Gly 370 375 380 His Ile Gln Tyr Asp Met Ala Tyr Ala Ala Gln Pro Phe Leu Leu Arg 385 390 395 400 Asn Gly Ala Asn Glu Gly Phe His Glu Ala Val Gly Glu Ile Met Ser 405 410 415 Leu Ser Ala Ala Thr Pro Lys His Leu Lys Ser Ile Gly Leu Leu Ser 420 425 430 Pro Asp Phe Gln Glu Asp Asn Glu Thr Glu Ile Asn Phe Leu Leu Lys 435 440 445 Gln Ala Leu Thr Ile Val Gly Thr Leu Pro Phe Thr Tyr Met Leu Glu 450 455 460 Lys Trp Arg Trp Met Val Phe Lys Gly Glu Ile Pro Lys Asp Gln Trp 465 470 475 480 Met Lys Lys Trp Trp Glu Met Lys Arg Glu Ile Val Gly Val Val Glu 485 490 495 Pro Val Pro His Asp Glu Thr Tyr Cys Asp Pro Ala Ser Leu Phe His 500 505 510 Val Ser Asn Asp Tyr Ser Phe Ile Arg Tyr Tyr Thr Arg Thr Leu Tyr 515 520 525 Gln Phe Gln Phe Gln Glu Ala Leu Cys Gln Ala Ala Lys His Glu Gly 530 535 540 Pro Leu His Lys Cys Asp Ile Ser Asn Ser Thr Glu Ala Gly Gln Lys 545 550 555 560 Leu Leu Asn Met Leu Lys Leu Gly Lys Ser Glu Pro Trp Thr Leu Ala 565 570 575 Leu Glu Asn Val Val Gly Ala Lys Asn Met Asn Val Arg Pro Leu Leu 580 585 590 Asn Tyr Phe Glu Pro Leu Phe Thr Trp Leu Lys Asp Gln Asn Lys Asn 595 600 605 Ser Phe Val Gly Trp Ser Thr Asp Trp Ser Pro Tyr Ala Asp Gln Ser 610 615 620 Ile Lys Val Arg Ile Ser Leu Lys Ser Ala Leu Gly Asp Lys Ala Tyr 625 630 635 640 Glu Trp Asn Asp Asn Glu Met Tyr Leu Phe Arg Ser Ser Val Ala Tyr 645 650 655 Ala Met Arg Thr Tyr Phe Leu Glu Ile Lys His Gln Thr Ile Leu Phe 660 665 670 Gly Glu Glu Asp Val Arg Val Ala Asp Leu Lys Pro Arg Ile Ser Phe 675 680 685 Asn Phe Tyr Val Thr Ala Pro Lys Asn Val Ser Asp Ile Ile Pro Arg 690 695 700 Thr Glu Val Glu Glu Ala Ile Arg Ile Ser Arg Ser Arg Ile Asn Asp 705 710 715 720 Ala Phe Arg Leu Asn Asp Asn Ser Leu Glu Phe Leu Gly Ile Gln Thr 725 730 735 Thr Leu Ala Pro Pro Tyr Gln Ser Pro Val Thr Asp Pro Leu Val Pro 740 745 750 Arg Gly Ser Gly Gly Gly Gly Asp Pro Glu Pro Lys Ser Cys Asp Lys 755 760 765 Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 770 775 780 Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 785 790 795 800 Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 805 810 815 Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 820 825 830 Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val 835 840 845 Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 850 855 860 Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys 865 870 875 880 Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 885 890 895 Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr 900 905 910 Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 915 920 925 Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 930 935 940 Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 945 950 955 960 Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 965 970 975 Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 980 985 990 Lys <210> 164 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 164 Gly His His His His His His His His 1 5 <210> 165 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 165 Gly Ser Gly Arg Glu Asn Leu Tyr Phe Gln Gly 1 5 10 <210> 166 <211> 31 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <400> 166 Gly Gly Gly Ser Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala 1 5 10 15 Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu 20 25 30 <210> 167 <211> 409 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (205)..(205) <223> X is absent or is an amino acid linker <400> 167 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 1 5 10 15 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 20 25 30 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 35 40 45 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 50 55 60 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 65 70 75 80 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 85 90 95 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 100 105 110 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 115 120 125 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 130 135 140 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 145 150 155 160 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 165 170 175 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 180 185 190 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Xaa Lys Met Glu 195 200 205 Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn Ser 210 215 220 Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val 225 230 235 240 His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile 245 250 255 Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly 260 265 270 Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala Val Glu Ser Gly Ala 275 280 285 Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala 290 295 300 Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu 305 310 315 320 Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro 325 330 335 Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe 340 345 350 Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val 355 360 365 Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala 370 375 380 Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe 385 390 395 400 Val Glu Lys Ile Arg Gly Ala Thr Glu 405 <210> 168 <211> 474 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (237)..(259) <223> optionally absent <220> <221> MISC_FEATURE <222> (464)..(474) <223> optionally absent <400> 168 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 35 40 45 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 50 55 60 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 65 70 75 80 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 85 90 95 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 100 105 110 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 115 120 125 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 130 135 140 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 145 150 155 160 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 165 170 175 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 180 185 190 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 195 200 205 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 210 215 220 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Gly Ser Gly Ser 225 230 235 240 Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu 245 250 255 Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val Ala 260 265 270 Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala Val Ala 275 280 285 Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe Thr Val Pro 290 295 300 Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly 305 310 315 320 Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys 325 330 335 Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu 340 345 350 Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly 355 360 365 Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr 370 375 380 Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys 385 390 395 400 Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly 405 410 415 Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala 420 425 430 Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg 435 440 445 Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu Gly 450 455 460 Gly Ser His His His His His His His His 465 470 <210> 169 <211> 409 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (205)..(205) <223> X is absent or is an amino acid linker <400> 169 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 1 5 10 15 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 20 25 30 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 35 40 45 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 50 55 60 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 65 70 75 80 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 85 90 95 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 100 105 110 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 115 120 125 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 130 135 140 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 145 150 155 160 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 165 170 175 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 180 185 190 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Xaa Lys Met Glu 195 200 205 Glu Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn Ser 210 215 220 Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly Val 225 230 235 240 His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile 245 250 255 Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly 260 265 270 Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala Val Glu Ser Gly Ala 275 280 285 Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala 290 295 300 Lys Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu 305 310 315 320 Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro 325 330 335 Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe 340 345 350 Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val 355 360 365 Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly Ser Ala 370 375 380 Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe 385 390 395 400 Val Glu Lys Ile Arg Gly Ala Thr Glu 405 <210> 170 <211> 478 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (237)..(263) <223> optionally absent <220> <221> MISC_FEATURE <222> (468)..(478) <223> optionally absent <400> 170 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 35 40 45 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 50 55 60 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 65 70 75 80 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 85 90 95 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 100 105 110 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 115 120 125 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 130 135 140 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 145 150 155 160 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 165 170 175 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 180 185 190 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 195 200 205 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 210 215 220 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Gly Gly Ser Gly 225 230 235 240 Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala 245 250 255 Lys Ala Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His 260 265 270 Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu 275 280 285 Lys Ala Val Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr 290 295 300 Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu 305 310 315 320 Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu 325 330 335 Gln Ala Arg Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro 340 345 350 His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe 355 360 365 Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys 370 375 380 Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro 385 390 395 400 Gln Phe Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val 405 410 415 Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala 420 425 430 Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr Pro 435 440 445 Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly 450 455 460 Ala Thr Glu Gly Gly Ser His His His His His His His His 465 470 475 <210> 171 <211> 1403 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1199)..(1199) <223> X is absent or is an amino acid linker <400> 171 Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr 1 5 10 15 Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser 20 25 30 Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn 35 40 45 Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys 50 55 60 Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala 65 70 75 80 Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr 85 90 95 Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn 100 105 110 Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln 145 150 155 160 Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu 165 170 175 Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser 180 185 190 Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser 195 200 205 Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg 210 215 220 Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp 225 230 235 240 Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr 245 250 255 Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile 260 265 270 Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 275 280 285 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 290 295 300 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 305 310 315 320 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 325 330 335 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 340 345 350 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 355 360 365 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 370 375 380 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 385 390 395 400 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 405 410 415 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 420 425 430 Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu 435 440 445 Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser 450 455 460 Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln 465 470 475 480 Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys 530 535 540 Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Ser Gly Ala Gly 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Xaa Lys Met Glu Glu 1190 1195 1200 Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn Ser 1205 1210 1215 Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly 1220 1225 1230 Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr 1235 1240 1245 Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile 1250 1255 1260 Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala Val 1265 1270 1275 Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu 1280 1285 1290 Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly 1295 1300 1305 Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His 1310 1315 1320 Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe 1325 1330 1335 Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro 1340 1345 1350 Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala 1355 1360 1365 Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr 1370 1375 1380 Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile 1385 1390 1395 Arg Gly Ala Thr Glu 1400 <210> 172 <211> 1511 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (1231)..(1296) <223> optionally absent <220> <221> MISC_FEATURE <222> (1501)..(1511) <223> optionally absent <400> 172 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr 35 40 45 Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser 50 55 60 Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn 65 70 75 80 Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys 85 90 95 Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala 100 105 110 Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr 115 120 125 Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn 130 135 140 Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu 145 150 155 160 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 165 170 175 Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln 180 185 190 Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu 195 200 205 Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser 210 215 220 Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser 225 230 235 240 Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg 245 250 255 Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp 260 265 270 Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr 275 280 285 Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile 290 295 300 Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 305 310 315 320 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 325 330 335 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 340 345 350 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 355 360 365 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 370 375 380 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 385 390 395 400 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 405 410 415 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 420 425 430 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 435 440 445 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 450 455 460 Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu 465 470 475 480 Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser 485 490 495 Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln 500 505 510 Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg 515 520 525 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 530 535 540 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 545 550 555 560 Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys 565 570 575 Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr 580 585 590 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 595 600 605 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 610 615 620 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 625 630 635 640 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 645 650 655 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 660 665 670 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 675 680 685 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Ser Gly Ala Gly 690 695 700 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 705 710 715 720 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 725 730 735 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 740 745 750 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 755 760 765 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 770 775 780 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 785 790 795 800 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 805 810 815 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 820 825 830 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 835 840 845 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 850 855 860 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 865 870 875 880 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 885 890 895 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 900 905 910 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 915 920 925 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 930 935 940 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 945 950 955 960 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 965 970 975 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 980 985 990 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 995 1000 1005 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu 1010 1015 1020 Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg 1025 1030 1035 Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu 1040 1045 1050 Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu 1055 1060 1065 Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His 1070 1075 1080 Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro 1085 1090 1095 Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val 1100 1105 1110 Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe 1115 1120 1125 Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly 1130 1135 1140 Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp 1145 1150 1155 Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys 1160 1165 1170 Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile 1175 1180 1185 Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp 1190 1195 1200 Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp 1205 1210 1215 Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Gly Ser Gly 1220 1225 1230 Arg Glu Asn Leu Tyr Phe Gln Gly Gly Gly Gly Ser Gly Tyr Ile 1235 1240 1245 Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly 1250 1255 1260 Glu Trp Val Leu Leu Ser Thr Phe Leu Gly Gly Ser Gly Ser Gly 1265 1270 1275 Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu 1280 1285 1290 Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys Ile Val 1295 1300 1305 Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu Lys Ala 1310 1315 1320 Val Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile Thr Phe 1325 1330 1335 Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser Val Leu 1340 1345 1350 Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val 1355 1360 1365 Glu Gln Ala Arg Lys Ala Val Glu Ser Gly Ala Glu Phe Ile Val 1370 1375 1380 Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Lys 1385 1390 1395 Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val 1400 1405 1410 Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly 1415 1420 1425 Glu Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly Pro Phe 1430 1435 1440 Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn 1445 1450 1455 Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly Val Gly 1460 1465 1470 Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu Lys Ala 1475 1480 1485 Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu Gly Gly Ser 1490 1495 1500 His His His His His His His His 1505 1510 <210> 173 <211> 1403 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1199)..(1199) <223> X is absent or is an amino acid linker <400> 173 Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr 1 5 10 15 Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser 20 25 30 Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn 35 40 45 Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys 50 55 60 Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala 65 70 75 80 Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr 85 90 95 Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn 100 105 110 Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln 145 150 155 160 Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu 165 170 175 Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser 180 185 190 Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser 195 200 205 Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg 210 215 220 Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp 225 230 235 240 Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr 245 250 255 Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile 260 265 270 Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 275 280 285 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 290 295 300 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 305 310 315 320 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 325 330 335 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 340 345 350 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 355 360 365 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 370 375 380 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 385 390 395 400 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 405 410 415 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 420 425 430 Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu 435 440 445 Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser 450 455 460 Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln 465 470 475 480 Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys 530 535 540 Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Ser Gly Ala Gly 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Xaa Lys Met Glu Glu 1190 1195 1200 Leu Phe Lys Lys His Lys Ile Val Ala Val Leu Arg Ala Asn Ser 1205 1210 1215 Val Glu Glu Ala Ile Glu Lys Ala Val Ala Val Phe Ala Gly Gly 1220 1225 1230 Val His Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr 1235 1240 1245 Val Ile Lys Ala Leu Ser Val Leu Lys Glu Lys Gly Ala Ile Ile 1250 1255 1260 Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Lys Ala Val 1265 1270 1275 Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu 1280 1285 1290 Ile Ser Gln Phe Ala Lys Glu Lys Gly Val Phe Tyr Met Pro Gly 1295 1300 1305 Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His 1310 1315 1320 Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe 1325 1330 1335 Val Lys Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro 1340 1345 1350 Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Lys Ala 1355 1360 1365 Gly Val Leu Ala Val Gly Val Gly Ser Ala Leu Val Lys Gly Thr 1370 1375 1380 Pro Asp Glu Val Arg Glu Lys Ala Lys Ala Phe Val Glu Lys Ile 1385 1390 1395 Arg Gly Ala Thr Glu 1400 <210> 174 <211> 1468 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (1231)..(1253) <223> optionally absent <220> <221> MISC_FEATURE <222> (1458)..(1468) <223> optionally absent <400> 174 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr 35 40 45 Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser 50 55 60 Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn 65 70 75 80 Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys 85 90 95 Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala 100 105 110 Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr 115 120 125 Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn 130 135 140 Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu 145 150 155 160 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 165 170 175 Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln 180 185 190 Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu 195 200 205 Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser 210 215 220 Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser 225 230 235 240 Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg 245 250 255 Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp 260 265 270 Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr 275 280 285 Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile 290 295 300 Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 305 310 315 320 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 325 330 335 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 340 345 350 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 355 360 365 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 370 375 380 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 385 390 395 400 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 405 410 415 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 420 425 430 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 435 440 445 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 450 455 460 Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu 465 470 475 480 Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser 485 490 495 Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln 500 505 510 Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg 515 520 525 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 530 535 540 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 545 550 555 560 Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys 565 570 575 Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr 580 585 590 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 595 600 605 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 610 615 620 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 625 630 635 640 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 645 650 655 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 660 665 670 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 675 680 685 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Ser Gly Ala Gly 690 695 700 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 705 710 715 720 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 725 730 735 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 740 745 750 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 755 760 765 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 770 775 780 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 785 790 795 800 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 805 810 815 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 820 825 830 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 835 840 845 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 850 855 860 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 865 870 875 880 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 885 890 895 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 900 905 910 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 915 920 925 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 930 935 940 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 945 950 955 960 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 965 970 975 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 980 985 990 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 995 1000 1005 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu 1010 1015 1020 Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg 1025 1030 1035 Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu 1040 1045 1050 Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu 1055 1060 1065 Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His 1070 1075 1080 Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro 1085 1090 1095 Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val 1100 1105 1110 Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe 1115 1120 1125 Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly 1130 1135 1140 Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp 1145 1150 1155 Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys 1160 1165 1170 Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile 1175 1180 1185 Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp 1190 1195 1200 Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp 1205 1210 1215 Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Gly Ser Gly 1220 1225 1230 Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala 1235 1240 1245 Glu Glu Ala Ala Arg Lys Met Glu Glu Leu Phe Lys Lys His Lys 1250 1255 1260 Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Ile Glu 1265 1270 1275 Lys Ala Val Ala Val Phe Ala Gly Gly Val His Leu Ile Glu Ile 1280 1285 1290 Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Ala Leu Ser 1295 1300 1305 Val Leu Lys Glu Lys Gly Ala Ile Ile Gly Ala Gly Thr Val Thr 1310 1315 1320 Ser Val Glu Gln Ala Arg Lys Ala Val Glu Ser Gly Ala Glu Phe 1325 1330 1335 Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys 1340 1345 1350 Glu Lys Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu 1355 1360 1365 Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe 1370 1375 1380 Pro Gly Glu Val Val Gly Pro Gln Phe Val Lys Ala Met Lys Gly 1385 1390 1395 Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu 1400 1405 1410 Asp Asn Val Ala Glu Trp Phe Lys Ala Gly Val Leu Ala Val Gly 1415 1420 1425 Val Gly Ser Ala Leu Val Lys Gly Thr Pro Asp Glu Val Arg Glu 1430 1435 1440 Lys Ala Lys Ala Phe Val Glu Lys Ile Arg Gly Ala Thr Glu Gly 1445 1450 1455 Gly Ser His His His His His His His His 1460 1465 <210> 175 <211> 408 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (205)..(205) <223> X is absent or is an amino acid linker <400> 175 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 1 5 10 15 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 20 25 30 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 35 40 45 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 50 55 60 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 65 70 75 80 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 85 90 95 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 100 105 110 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 115 120 125 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 130 135 140 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 145 150 155 160 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 165 170 175 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 180 185 190 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Xaa Met Glu Glu 195 200 205 Leu Phe Lys Glu His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val 210 215 220 Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe Leu Gly Gly Val Asp 225 230 235 240 Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys 245 250 255 Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile Ile Gly Ala Gly Thr 260 265 270 Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val Glu Ser Gly Ala Glu 275 280 285 Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys 290 295 300 Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu 305 310 315 320 Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly 325 330 335 Glu Val Val Gly Pro Gln Phe Val Glu Ala Met Lys Gly Pro Phe Pro 340 345 350 Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala 355 360 365 Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly Val Gly Glu Ala Leu 370 375 380 Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys Ala Lys Ala Phe Val 385 390 395 400 Glu Lys Ile Glu Gly Ala Thr Glu 405 <210> 176 <211> 469 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (237)..(255) <223> optionally absent <220> <221> MISC_FEATURE <222> (459)..(469) <223> optionally absent <400> 176 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 35 40 45 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 50 55 60 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 65 70 75 80 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 85 90 95 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 100 105 110 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 115 120 125 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 130 135 140 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 145 150 155 160 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 165 170 175 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 180 185 190 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 195 200 205 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 210 215 220 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Gly Gly Ser Gly 225 230 235 240 Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu Ala Ala Arg Met 245 250 255 Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala Val Leu Arg Ala Asn 260 265 270 Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe Leu Gly Gly 275 280 285 Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val 290 295 300 Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile Ile Gly Ala 305 310 315 320 Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val Glu Ser Gly 325 330 335 Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe 340 345 350 Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr 355 360 365 Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe 370 375 380 Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala Met Lys Gly Pro 385 390 395 400 Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn 405 410 415 Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly Val Gly Glu 420 425 430 Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys Ala Lys Ala 435 440 445 Phe Val Glu Lys Ile Glu Gly Ala Thr Glu Gly Gly Ser His His His 450 455 460 His His His His His 465 <210> 177 <211> 408 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (205)..(205) <223> X is absent or is an amino acid linker <400> 177 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 1 5 10 15 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 20 25 30 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 35 40 45 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 50 55 60 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 65 70 75 80 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 85 90 95 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 100 105 110 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 115 120 125 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 130 135 140 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 145 150 155 160 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 165 170 175 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 180 185 190 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Xaa Met Glu Glu 195 200 205 Leu Phe Lys Glu His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val 210 215 220 Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe Leu Gly Gly Val Asp 225 230 235 240 Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys 245 250 255 Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile Ile Gly Ala Gly Thr 260 265 270 Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val Glu Ser Gly Ala Glu 275 280 285 Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys 290 295 300 Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu 305 310 315 320 Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly 325 330 335 Glu Val Val Gly Pro Gln Phe Val Glu Ala Met Lys Gly Pro Phe Pro 340 345 350 Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala 355 360 365 Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly Val Gly Glu Ala Leu 370 375 380 Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys Ala Lys Ala Phe Val 385 390 395 400 Glu Lys Ile Glu Gly Ala Thr Glu 405 <210> 178 <211> 473 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (237)..(259) <223> optionally absent <220> <221> MISC_FEATURE <222> (463)..(473) <223> optionally absent <400> 178 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 35 40 45 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 50 55 60 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 65 70 75 80 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 85 90 95 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 100 105 110 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 115 120 125 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 130 135 140 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 145 150 155 160 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 165 170 175 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 180 185 190 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 195 200 205 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 210 215 220 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Gly Ser Gly Ser 225 230 235 240 Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu 245 250 255 Ala Ala Arg Met Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala Val 260 265 270 Leu Arg Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala Leu Ala Val 275 280 285 Phe Leu Gly Gly Val Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp 290 295 300 Ala Asp Thr Val Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala 305 310 315 320 Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala 325 330 335 Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu 340 345 350 Ile Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val 355 360 365 Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr Ile 370 375 380 Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala 385 390 395 400 Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val 405 410 415 Asn Leu Asp Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val 420 425 430 Gly Val Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu 435 440 445 Lys Ala Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu Gly Gly 450 455 460 Ser His His His His His His His His 465 470 <210> 179 <211> 408 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (205)..(205) <223> X is absent or is an amino acid linker <400> 179 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 1 5 10 15 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 20 25 30 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 35 40 45 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 50 55 60 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 65 70 75 80 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 85 90 95 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 100 105 110 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 115 120 125 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 130 135 140 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 145 150 155 160 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 165 170 175 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 180 185 190 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Xaa Met Glu Glu 195 200 205 Leu Phe Lys Glu His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val 210 215 220 Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe Leu Gly Gly Val Asp 225 230 235 240 Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys 245 250 255 Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile Ile Gly Ala Gly Thr 260 265 270 Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val Glu Ser Gly Ala Glu 275 280 285 Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys 290 295 300 Glu Glu Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu 305 310 315 320 Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly 325 330 335 Glu Val Val Gly Pro Gln Phe Val Glu Ala Met Lys Gly Pro Phe Pro 340 345 350 Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val Ala 355 360 365 Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly Val Gly Glu Ala Leu 370 375 380 Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys Ala Lys Ala Phe Val 385 390 395 400 Glu Lys Ile Glu Gly Ala Thr Glu 405 <210> 180 <211> 477 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (237)..(263) <223> optionally absent <220> <221> MISC_FEATURE <222> (467)..(477) <223> optionally absent <400> 180 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn 35 40 45 Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser 50 55 60 Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser 65 70 75 80 Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys 85 90 95 Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val 100 105 110 Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr 115 120 125 Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn 130 135 140 Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu 145 150 155 160 Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu 165 170 175 Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn 180 185 190 Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val 195 200 205 Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His 210 215 220 Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Gly Gly Ser Gly 225 230 235 240 Gly Ser Gly Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala 245 250 255 Lys Ala Glu Glu Ala Ala Arg Met Glu Glu Leu Phe Lys Glu His Lys 260 265 270 Ile Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Lys Lys Lys 275 280 285 Ala Leu Ala Val Phe Leu Gly Gly Val Asp Leu Ile Glu Ile Thr Phe 290 295 300 Thr Val Pro Asp Ala Asp Thr Val Ile Lys Glu Leu Ser Phe Leu Lys 305 310 315 320 Glu Met Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu Gln 325 330 335 Ala Arg Glu Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser Pro His 340 345 350 Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr 355 360 365 Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu 370 375 380 Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln 385 390 395 400 Phe Val Glu Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro 405 410 415 Thr Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Glu Ala Gly 420 425 430 Val Gln Ala Val Gly Val Gly Glu Ala Leu Asn Glu Gly Thr Pro Val 435 440 445 Glu Val Ala Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Glu Gly Ala 450 455 460 Thr Glu Gly Gly Ser His His His His His His His His 465 470 475 <210> 181 <211> 1402 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1199)..(1199) <223> X is absent or is an amino acid linker <400> 181 Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr 1 5 10 15 Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser 20 25 30 Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn 35 40 45 Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys 50 55 60 Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala 65 70 75 80 Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr 85 90 95 Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn 100 105 110 Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln 145 150 155 160 Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu 165 170 175 Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser 180 185 190 Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser 195 200 205 Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg 210 215 220 Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp 225 230 235 240 Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr 245 250 255 Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile 260 265 270 Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 275 280 285 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 290 295 300 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 305 310 315 320 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 325 330 335 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 340 345 350 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 355 360 365 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 370 375 380 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 385 390 395 400 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 405 410 415 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 420 425 430 Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu 435 440 445 Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser 450 455 460 Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln 465 470 475 480 Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys 530 535 540 Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Ser Gly Ala Gly 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Xaa Met Glu Glu Leu 1190 1195 1200 Phe Lys Glu His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val 1205 1210 1215 Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe Leu Gly Gly Val 1220 1225 1230 Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val 1235 1240 1245 Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile Ile Gly 1250 1255 1260 Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val Glu 1265 1270 1275 Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile 1280 1285 1290 Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val 1295 1300 1305 Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr 1310 1315 1320 Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val 1325 1330 1335 Glu Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr 1340 1345 1350 Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Glu Ala Gly 1355 1360 1365 Val Gln Ala Val Gly Val Gly Glu Ala Leu Asn Glu Gly Thr Pro 1370 1375 1380 Val Glu Val Ala Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Glu 1385 1390 1395 Gly Ala Thr Glu 1400 <210> 182 <211> 1510 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (1231)..(1296) <223> optionally absent <220> <221> MISC_FEATURE <222> (1500)..(1510) <223> optionally absent <400> 182 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr 35 40 45 Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser 50 55 60 Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn 65 70 75 80 Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys 85 90 95 Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala 100 105 110 Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr 115 120 125 Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn 130 135 140 Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu 145 150 155 160 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 165 170 175 Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln 180 185 190 Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu 195 200 205 Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser 210 215 220 Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser 225 230 235 240 Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg 245 250 255 Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp 260 265 270 Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr 275 280 285 Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile 290 295 300 Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 305 310 315 320 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 325 330 335 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 340 345 350 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 355 360 365 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 370 375 380 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 385 390 395 400 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 405 410 415 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 420 425 430 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 435 440 445 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 450 455 460 Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu 465 470 475 480 Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser 485 490 495 Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln 500 505 510 Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg 515 520 525 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 530 535 540 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 545 550 555 560 Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys 565 570 575 Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr 580 585 590 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 595 600 605 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 610 615 620 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 625 630 635 640 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 645 650 655 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 660 665 670 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 675 680 685 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Ser Gly Ala Gly 690 695 700 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 705 710 715 720 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 725 730 735 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 740 745 750 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 755 760 765 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 770 775 780 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 785 790 795 800 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 805 810 815 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 820 825 830 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 835 840 845 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 850 855 860 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 865 870 875 880 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 885 890 895 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 900 905 910 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 915 920 925 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 930 935 940 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 945 950 955 960 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 965 970 975 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 980 985 990 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 995 1000 1005 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu 1010 1015 1020 Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg 1025 1030 1035 Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu 1040 1045 1050 Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu 1055 1060 1065 Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His 1070 1075 1080 Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro 1085 1090 1095 Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val 1100 1105 1110 Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe 1115 1120 1125 Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly 1130 1135 1140 Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp 1145 1150 1155 Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys 1160 1165 1170 Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile 1175 1180 1185 Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp 1190 1195 1200 Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp 1205 1210 1215 Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Gly Ser Gly 1220 1225 1230 Arg Glu Asn Leu Tyr Phe Gln Gly Gly Gly Gly Ser Gly Tyr Ile 1235 1240 1245 Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys Asp Gly 1250 1255 1260 Glu Trp Val Leu Leu Ser Thr Phe Leu Gly Gly Ser Gly Ser Gly 1265 1270 1275 Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala Glu Glu 1280 1285 1290 Ala Ala Arg Met Glu Glu Leu Phe Lys Glu His Lys Ile Val Ala 1295 1300 1305 Val Leu Arg Ala Asn Ser Val Glu Glu Ala Lys Lys Lys Ala Leu 1310 1315 1320 Ala Val Phe Leu Gly Gly Val Asp Leu Ile Glu Ile Thr Phe Thr 1325 1330 1335 Val Pro Asp Ala Asp Thr Val Ile Lys Glu Leu Ser Phe Leu Lys 1340 1345 1350 Glu Met Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser Val Glu 1355 1360 1365 Gln Ala Arg Glu Ala Val Glu Ser Gly Ala Glu Phe Ile Val Ser 1370 1375 1380 Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu Glu Gly 1385 1390 1395 Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu Val Lys 1400 1405 1410 Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro Gly Glu 1415 1420 1425 Val Val Gly Pro Gln Phe Val Glu Ala Met Lys Gly Pro Phe Pro 1430 1435 1440 Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp Asn Val 1445 1450 1455 Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly Val Gly Glu 1460 1465 1470 Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys Ala Lys 1475 1480 1485 Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu Gly Gly Ser His 1490 1495 1500 His His His His His His His 1505 1510 <210> 183 <211> 1402 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1199)..(1199) <223> X is absent or is an amino acid linker <400> 183 Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr 1 5 10 15 Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser 20 25 30 Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn 35 40 45 Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys 50 55 60 Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala 65 70 75 80 Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr 85 90 95 Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn 100 105 110 Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu 115 120 125 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 130 135 140 Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln 145 150 155 160 Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu 165 170 175 Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser 180 185 190 Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser 195 200 205 Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg 210 215 220 Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp 225 230 235 240 Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr 245 250 255 Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile 260 265 270 Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 275 280 285 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 290 295 300 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 305 310 315 320 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 325 330 335 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 340 345 350 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 355 360 365 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 370 375 380 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 385 390 395 400 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 405 410 415 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 420 425 430 Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu 435 440 445 Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser 450 455 460 Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln 465 470 475 480 Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg 485 490 495 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 500 505 510 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 515 520 525 Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys 530 535 540 Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr 545 550 555 560 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 565 570 575 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 580 585 590 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 595 600 605 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 610 615 620 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 625 630 635 640 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 645 650 655 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Ser Gly Ala Gly 660 665 670 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 675 680 685 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 690 695 700 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 705 710 715 720 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 725 730 735 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 740 745 750 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 755 760 765 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 770 775 780 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 785 790 795 800 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 805 810 815 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 820 825 830 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 835 840 845 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 850 855 860 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 865 870 875 880 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 885 890 895 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 900 905 910 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 915 920 925 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 930 935 940 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 945 950 955 960 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 965 970 975 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 980 985 990 Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 995 1000 1005 Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln 1010 1015 1020 Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser 1025 1030 1035 Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr 1040 1045 1050 Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile 1055 1060 1065 Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe Val 1070 1075 1080 Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu 1085 1090 1095 Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys 1100 1105 1110 Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu 1115 1120 1125 Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe 1130 1135 1140 Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly 1145 1150 1155 Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu 1160 1165 1170 Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln 1175 1180 1185 Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Xaa Met Glu Glu Leu 1190 1195 1200 Phe Lys Glu His Lys Ile Val Ala Val Leu Arg Ala Asn Ser Val 1205 1210 1215 Glu Glu Ala Lys Lys Lys Ala Leu Ala Val Phe Leu Gly Gly Val 1220 1225 1230 Asp Leu Ile Glu Ile Thr Phe Thr Val Pro Asp Ala Asp Thr Val 1235 1240 1245 Ile Lys Glu Leu Ser Phe Leu Lys Glu Met Gly Ala Ile Ile Gly 1250 1255 1260 Ala Gly Thr Val Thr Ser Val Glu Gln Ala Arg Glu Ala Val Glu 1265 1270 1275 Ser Gly Ala Glu Phe Ile Val Ser Pro His Leu Asp Glu Glu Ile 1280 1285 1290 Ser Gln Phe Ala Lys Glu Glu Gly Val Phe Tyr Met Pro Gly Val 1295 1300 1305 Met Thr Pro Thr Glu Leu Val Lys Ala Met Lys Leu Gly His Thr 1310 1315 1320 Ile Leu Lys Leu Phe Pro Gly Glu Val Val Gly Pro Gln Phe Val 1325 1330 1335 Glu Ala Met Lys Gly Pro Phe Pro Asn Val Lys Phe Val Pro Thr 1340 1345 1350 Gly Gly Val Asn Leu Asp Asn Val Ala Glu Trp Phe Glu Ala Gly 1355 1360 1365 Val Gln Ala Val Gly Val Gly Glu Ala Leu Asn Glu Gly Thr Pro 1370 1375 1380 Val Glu Val Ala Glu Lys Ala Lys Ala Phe Val Glu Lys Ile Glu 1385 1390 1395 Gly Ala Thr Glu 1400 <210> 184 <211> 1467 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(32) <223> optionally absent <220> <221> MISC_FEATURE <222> (1231)..(1253) <223> optionally absent <220> <221> MISC_FEATURE <222> (1457)..(1467) <223> optionally absent <400> 184 Met Gly Ile Leu Pro Ser Pro Gly Met Pro Ala Leu Leu Ser Leu Val 1 5 10 15 Ser Leu Leu Ser Val Leu Leu Met Gly Cys Val Ala Glu Thr Gly Thr 20 25 30 Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr 35 40 45 Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser 50 55 60 Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn 65 70 75 80 Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys 85 90 95 Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala 100 105 110 Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr 115 120 125 Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn 130 135 140 Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu 145 150 155 160 Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe 165 170 175 Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln 180 185 190 Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu 195 200 205 Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser 210 215 220 Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser 225 230 235 240 Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg 245 250 255 Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp 260 265 270 Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr 275 280 285 Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile 290 295 300 Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys 305 310 315 320 Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn 325 330 335 Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr 340 345 350 Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser 355 360 365 Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr 370 375 380 Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly 385 390 395 400 Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala 405 410 415 Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly 420 425 430 Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe 435 440 445 Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val 450 455 460 Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu 465 470 475 480 Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser 485 490 495 Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln 500 505 510 Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg 515 520 525 Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys 530 535 540 Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe 545 550 555 560 Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys 565 570 575 Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr 580 585 590 Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro 595 600 605 Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser 610 615 620 Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro 625 630 635 640 Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser 645 650 655 Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala 660 665 670 Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly 675 680 685 Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Ser Gly Ala Gly 690 695 700 Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 705 710 715 720 Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 725 730 735 Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 740 745 750 Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 755 760 765 Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 770 775 780 Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 785 790 795 800 Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 805 810 815 Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 820 825 830 Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 835 840 845 Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 850 855 860 Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 865 870 875 880 Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 885 890 895 Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 900 905 910 Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 915 920 925 Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 930 935 940 Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 945 950 955 960 Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 965 970 975 Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 980 985 990 Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala 995 1000 1005 Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu 1010 1015 1020 Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg 1025 1030 1035 Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu 1040 1045 1050 Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu 1055 1060 1065 Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu His 1070 1075 1080 Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro 1085 1090 1095 Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val 1100 1105 1110 Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe 1115 1120 1125 Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly 1130 1135 1140 Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp 1145 1150 1155 Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys 1160 1165 1170 Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile 1175 1180 1185 Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp 1190 1195 1200 Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp 1205 1210 1215 Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Gly Ser Gly 1220 1225 1230 Ser Gly Gly Ser Gly Gly Ser Gly Ser Glu Lys Ala Ala Lys Ala 1235 1240 1245 Glu Glu Ala Ala Arg Met Glu Glu Leu Phe Lys Glu His Lys Ile 1250 1255 1260 Val Ala Val Leu Arg Ala Asn Ser Val Glu Glu Ala Lys Lys Lys 1265 1270 1275 Ala Leu Ala Val Phe Leu Gly Gly Val Asp Leu Ile Glu Ile Thr 1280 1285 1290 Phe Thr Val Pro Asp Ala Asp Thr Val Ile Lys Glu Leu Ser Phe 1295 1300 1305 Leu Lys Glu Met Gly Ala Ile Ile Gly Ala Gly Thr Val Thr Ser 1310 1315 1320 Val Glu Gln Ala Arg Glu Ala Val Glu Ser Gly Ala Glu Phe Ile 1325 1330 1335 Val Ser Pro His Leu Asp Glu Glu Ile Ser Gln Phe Ala Lys Glu 1340 1345 1350 Glu Gly Val Phe Tyr Met Pro Gly Val Met Thr Pro Thr Glu Leu 1355 1360 1365 Val Lys Ala Met Lys Leu Gly His Thr Ile Leu Lys Leu Phe Pro 1370 1375 1380 Gly Glu Val Val Gly Pro Gln Phe Val Glu Ala Met Lys Gly Pro 1385 1390 1395 Phe Pro Asn Val Lys Phe Val Pro Thr Gly Gly Val Asn Leu Asp 1400 1405 1410 Asn Val Ala Glu Trp Phe Glu Ala Gly Val Gln Ala Val Gly Val 1415 1420 1425 Gly Glu Ala Leu Asn Glu Gly Thr Pro Val Glu Val Ala Glu Lys 1430 1435 1440 Ala Lys Ala Phe Val Glu Lys Ile Glu Gly Ala Thr Glu Gly Gly 1445 1450 1455 Ser His His His His His His His His 1460 1465 <210> 185 <211> 199 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(25) <223> optionally absent <220> <221> MISC_FEATURE <222> (180)..(199) <223> optionally absent <400> 185 Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 1 5 10 15 Gly Ser Thr Gly Asp Tyr Lys Asp Glu Lys Lys Tyr Asp Gly Ser Lys 20 25 30 Leu Arg Ile Gly Ile Leu His Ala Arg Glu Asn Ala Glu Ile Ile Leu 35 40 45 Ala Leu Val Leu Gly Ala Leu Lys Arg Leu Gln Glu Phe Gly Val Lys 50 55 60 Arg Glu Asn Ile Ile Ile Glu Thr Val Pro Gly Ser Phe Glu Leu Pro 65 70 75 80 Tyr Gly Ser Lys Leu Phe Val Glu Lys Gln Lys Arg Leu Gly Lys Pro 85 90 95 Leu Asp Ala Ile Ile Pro Ile Gly Val Leu Ile Lys Gly Ser Thr Met 100 105 110 His Phe Glu Tyr Ile Cys Asp Ser Thr Thr His Gln Leu Met Lys Leu 115 120 125 Asn Phe Glu Leu Gly Ile Pro Val Ile Phe Gly Val Leu Thr Cys Leu 130 135 140 Thr Asp Glu Gln Ala Glu Ala Arg Ala Gly Leu Ile Glu Gly Lys Met 145 150 155 160 His Asn His Gly Glu Asp Trp Gly Ala Ala Ala Val Glu Met Ala Thr 165 170 175 Lys Phe Asn Leu Glu Gly Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp 180 185 190 Leu His His His His His His 195 <210> 186 <211> 199 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(25) <223> optionally absent <220> <221> MISC_FEATURE <222> (180)..(199) <223> optionally absent <400> 186 Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 1 5 10 15 Gly Ser Thr Gly Asp Tyr Lys Asp Glu Lys Lys Tyr Asp Gly Ser Lys 20 25 30 Leu Arg Ile Gly Ile Leu His Ala Arg Trp Asn Ala Glu Ile Ile Leu 35 40 45 Ala Leu Val Leu Gly Ala Asn Lys Arg Leu Gln Glu Phe Gly Val Lys 50 55 60 Arg Glu Asn Ile Ile Ile Glu Thr Val Pro Gly Ser Phe Glu Leu Pro 65 70 75 80 Tyr Gly Ser Lys Leu Phe Val Glu Lys Gln Lys Arg Leu Gly Lys Pro 85 90 95 Leu Asp Ala Ile Ile Pro Ile Gly Val Leu Ile Lys Gly Ser Thr Met 100 105 110 His Phe Glu Tyr Ile Cys Asp Ser Thr Thr His Gln Leu Met Lys Leu 115 120 125 Asn Phe Glu Leu Gly Ile Pro Val Ile Phe Gly Val Leu Thr Cys Leu 130 135 140 Thr Asp Glu Gln Ala Glu Ala Arg Ala Gly Leu Ile Glu Gly Lys Met 145 150 155 160 His Asn His Gly Glu Asp Trp Gly Ala Ala Ala Val Glu Met Ala Thr 165 170 175 Lys Phe Asn Leu Glu Gly Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp 180 185 190 Leu His His His His His His 195 <210> 187 <211> 199 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(25) <223> optionally absent <220> <221> MISC_FEATURE <222> (180)..(199) <223> optionally absent <400> 187 Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 1 5 10 15 Gly Ser Thr Gly Asp Tyr Lys Asp Glu Lys Lys Tyr Asp Gly Ser Lys 20 25 30 Leu Arg Ile Gly Ile Leu His Ala Arg Trp Asn Ala Glu Ile Ile Leu 35 40 45 Ala Leu Val Leu Gly Ala Leu Lys Arg Leu Gln Glu Phe Gly Val Lys 50 55 60 Arg Glu Asn Ile Ile Ile Glu Thr Val Pro Gly Ser Phe Glu Leu Pro 65 70 75 80 Tyr Gly Ser Lys Leu Phe Val Glu Lys Gln Lys Arg Leu Gly Lys Pro 85 90 95 Leu Asp Ala Ile Ile Pro Ile Gly Val Leu Ile Lys Gly Ser Thr Met 100 105 110 His Phe Glu Tyr Ile Cys Asp Ser Thr Thr His Gln Leu Met Lys Leu 115 120 125 Asn Phe Glu Leu Gly Ile Pro Val Ile Phe Gly Val Leu Asn Cys Asp 130 135 140 Lys Asp Glu Gln Ala Glu Ala Arg Ala Gly Leu Ile Glu Gly Lys Met 145 150 155 160 His Asn His Gly Glu Asp Trp Gly Ala Ala Ala Val Glu Met Ala Thr 165 170 175 Lys Phe Asn Leu Glu Gly Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp 180 185 190 Leu His His His His His His 195 <210> 188 <211> 199 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(25) <223> optionally absent <220> <221> MISC_FEATURE <222> (180)..(199) <223> optionally absent <400> 188 Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 1 5 10 15 Gly Ser Thr Gly Asp Tyr Lys Asp Glu Lys Lys Tyr Asp Gly Ser Lys 20 25 30 Leu Arg Ile Gly Ile Leu His Ala Arg Trp Asn Ala Glu Ile Ile Leu 35 40 45 Ala Leu Val Leu Gly Ala Leu Lys Arg Leu Gln Glu Phe Gly Val Lys 50 55 60 Arg Glu Asn Ile Ile Ile Glu Thr Val Pro Gly Ser Phe Glu Leu Pro 65 70 75 80 Tyr Gly Ser Lys Leu Phe Val Glu Lys Gln Lys Arg Leu Gly Lys Pro 85 90 95 Leu Asp Ala Ile Ile Pro Ile Gly Val Leu Ile Lys Gly Ser Thr Met 100 105 110 His Phe Glu Tyr Ile Cys Asp Ser Thr Thr His Gln Leu Met Lys Leu 115 120 125 Asn Phe Glu Leu Gly Ile Pro Val Ile Phe Gly Val Leu Asn Cys Leu 130 135 140 Thr Asp Glu Gln Ala Glu Ala Arg Ala Gly Leu Ile Glu Gly Lys Met 145 150 155 160 His Asn His Gly Glu Asp Trp Gly Ala Ala Ala Val Glu Met Ala Thr 165 170 175 Lys Phe Asn Leu Glu Gly Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp 180 185 190 Leu His His His His His His 195 <210> 189 <211> 199 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(25) <223> optionally absent <220> <221> MISC_FEATURE <222> (180)..(199) <223> optionally absent <400> 189 Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 1 5 10 15 Gly Ser Thr Gly Asp Tyr Lys Asp Glu Lys Lys Tyr Asp Gly Ser Lys 20 25 30 Leu Arg Ile Gly Ile Leu His Ala Arg Trp Asn Ala Glu Ile Ile Leu 35 40 45 Ala Leu Val Leu Gly Ala Leu Lys Arg Leu Gln Glu Phe Gly Val Lys 50 55 60 Arg Glu Asn Ile Ile Ile Glu Thr Val Pro Gly Ser Phe Glu Leu Pro 65 70 75 80 Tyr Gly Ser Lys Leu Phe Val Glu Lys Gln Lys Arg Leu Gly Lys Pro 85 90 95 Leu Asp Ala Ile Ile Pro Ile Gly Val Leu Ile Lys Gly Ser Thr Met 100 105 110 His Phe Glu Tyr Ile Cys Asp Ser Thr Thr His Gln Leu Met Lys Leu 115 120 125 Asn Phe Glu Leu Gly Ile Pro Val Ile Phe Gly Val Leu Thr Cys Asp 130 135 140 Thr Asp Glu Gln Ala Glu Ala Arg Ala Gly Leu Ile Glu Gly Lys Met 145 150 155 160 His Asn His Gly Glu Asp Trp Gly Ala Ala Ala Val Glu Met Ala Thr 165 170 175 Lys Phe Asn Leu Glu Gly Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp 180 185 190 Leu His His His His His His 195 <210> 190 <211> 199 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(25) <223> optionally absent <220> <221> MISC_FEATURE <222> (180)..(199) <223> optionally absent <400> 190 Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 1 5 10 15 Gly Ser Thr Gly Asp Tyr Lys Asp Glu Lys Lys Tyr Asp Gly Ser Lys 20 25 30 Leu Arg Ile Gly Ile Leu His Ala Arg Trp Asn Ala Glu Ile Ile Leu 35 40 45 Ala Leu Val Leu Gly Ala Leu Lys Arg Leu Gln Glu Phe Gly Val Lys 50 55 60 Arg Glu Asn Ile Ile Ile Glu Thr Val Pro Gly Ser Phe Glu Leu Pro 65 70 75 80 Tyr Gly Ser Lys Leu Phe Val Glu Lys Gln Lys Arg Leu Gly Lys Pro 85 90 95 Leu Asp Ala Ile Ile Pro Ile Gly Val Leu Ile Lys Gly Ser Thr Met 100 105 110 His Phe Glu Tyr Ile Cys Asp Ser Thr Thr His Gln Leu Met Lys Leu 115 120 125 Asn Phe Glu Leu Gly Ile Pro Val Ile Phe Gly Val Leu Thr Cys Leu 130 135 140 Lys Asp Glu Gln Ala Glu Ala Arg Ala Gly Leu Ile Glu Gly Lys Met 145 150 155 160 His Asn His Gly Glu Asp Trp Gly Ala Ala Ala Val Glu Met Ala Thr 165 170 175 Lys Phe Asn Leu Glu Gly Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp 180 185 190 Leu His His His His His His 195 <210> 191 <211> 200 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(27) <223> optionally absent <220> <221> MISC_FEATURE <222> (181)..(200) <223> optionally absent <400> 191 Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 1 5 10 15 Gly Ser Thr Gly Asp Tyr Lys Asp Glu Met Gly Lys Tyr Asp Gly Ser 20 25 30 Lys Leu Arg Ile Gly Ile Leu His Ala Arg Gly Asn Ala Glu Ile Ile 35 40 45 Leu Ala Leu Val Leu Gly Ala Leu Lys Arg Leu Gln Glu Phe Gly Val 50 55 60 Lys Arg Glu Asn Ile Ile Ile Glu Thr Val Pro Gly Ser Phe Glu Leu 65 70 75 80 Pro Tyr Gly Ser Lys Leu Phe Val Glu Lys Gln Lys Arg Leu Gly Lys 85 90 95 Pro Leu Asp Ala Ile Ile Pro Ile Gly Val Leu Ile Arg Gly Ser Thr 100 105 110 Pro His Phe Asp Tyr Ile Ala Asp Ser Thr Thr His Gln Leu Met Lys 115 120 125 Leu Asn Phe Glu Leu Gly Ile Pro Val Ile Phe Gly Val Ile Thr Ala 130 135 140 Asp Thr Asp Glu Gln Ala Glu Ala Arg Ala Gly Leu Ile Glu Gly Lys 145 150 155 160 Met His Asn His Gly Glu Asp Trp Gly Ala Ala Ala Val Glu Met Ala 165 170 175 Thr Lys Phe Asn Leu Glu Gly Ser Glu Gln Lys Leu Ile Ser Glu Glu 180 185 190 Asp Leu His His His His His His 195 200 <210> 192 <211> 200 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(27) <223> optionally absent <220> <221> MISC_FEATURE <222> (181)..(200) <223> optionally absent <400> 192 Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 1 5 10 15 Gly Ser Thr Gly Asp Tyr Lys Asp Glu Met Gly Lys Tyr Asp Gly Ser 20 25 30 Lys Leu Arg Ile Gly Ile Leu His Ala Arg Glu Asn Ala Glu Ile Ile 35 40 45 Leu Ala Leu Val Leu Gly Ala Leu Lys Arg Leu Gln Glu Phe Gly Val 50 55 60 Lys Arg Glu Asn Ile Ile Ile Glu Thr Val Pro Gly Ser Phe Glu Leu 65 70 75 80 Pro Tyr Gly Ser Lys Leu Phe Val Glu Lys Gln Lys Arg Leu Gly Lys 85 90 95 Pro Leu Asp Ala Ile Ile Pro Ile Gly Val Leu Ile Arg Gly Ser Thr 100 105 110 Pro His Phe Asp Tyr Ile Ala Asp Ser Thr Thr His Gln Leu Met Lys 115 120 125 Leu Asn Phe Glu Leu Gly Ile Pro Val Ile Phe Gly Val Ile Thr Ala 130 135 140 Asp Thr Asp Glu Gln Ala Glu Ala Arg Ala Gly Leu Ile Glu Gly Lys 145 150 155 160 Met His Asn His Gly Glu Asp Trp Gly Ala Ala Ala Val Glu Met Ala 165 170 175 Thr Lys Phe Asn Leu Glu Gly Ser Glu Gln Lys Leu Ile Ser Glu Glu 180 185 190 Asp Leu His His His His His His 195 200 <210> 193 <211> 197 <212> PRT <213> Artificial Sequence <220> <223> Synthetic <220> <221> MISC_FEATURE <222> (1)..(27) <223> optionally absent <220> <221> MISC_FEATURE <222> (178)..(197) <223> optionally absent <400> 193 Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 1 5 10 15 Gly Ser Thr Gly Asp Tyr Lys Asp Glu Met Gly Lys Tyr Asp Gly Ser 20 25 30 Lys Leu Arg Ile Gly Ile Leu His Ala Arg Gly Asn Ala Glu Ile Ile 35 40 45 Leu Glu Leu Val Leu Gly Ala Leu Lys Arg Leu Gln Glu Phe Gly Val 50 55 60 Lys Arg Glu Asn Ile Ile Ile Glu Thr Val Pro Gly Ser Phe Glu Leu 65 70 75 80 Pro Tyr Gly Ser Lys Leu Phe Val Glu Lys Gln Lys Arg Leu Gly Lys 85 90 95 Pro Leu Asp Ala Ile Ile Pro Ile Gly Val Leu Ile Arg Gly Ser Thr 100 105 110 Ala His Phe Asp Tyr Ile Ala Asp Ser Thr Thr His Gln Leu Met Lys 115 120 125 Leu Asn Phe Glu Leu Gly Ile Pro Val Ile Phe Gly Val Leu Thr Thr 130 135 140 Glu Ser Asp Glu Gln Ala Glu Glu Arg Ala Gly Thr Lys Ala Gly Asn 145 150 155 160 His Gly Glu Asp Trp Gly Ala Ala Ala Val Glu Met Ala Thr Lys Phe 165 170 175 Asn Leu Glu Gly Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu His 180 185 190 His His His His His 195

Claims (59)

  1. 서열번호 1-84, 138-146 및 167-184로 이루어진 군으로부터 선택되는 아미노산 서열에 대해 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99% 또는 적어도 100% 동일한 아미노산 서열을 포함하고, 서열에서 X1이 생략되거나 또는 아미노산 링커이고, 괄호 안 서열이 선택적이며, 존재할 수 있거나, 또는 선택 잔기들 중 일부 또는 전부 생략될 수 있는, 폴리펩타이드.
  2. 제1항에 있어서, 서열번호 1-12 및 142-151로 이루어진 군으로부터 선택되는 아미노산 서열을 포함하는, 폴리펩타이드.
  3. 제1항에 있어서, 서열번호 1-8로 이루어진 군으로부터 선택되는 아미노산 서열을 포함하는, 폴리펩타이드.
  4. 제1항에 있어서, 서열번호 1-4로 이루어진 군으로부터 선택되는 아미노산 서열을 포함하는, 폴리펩타이드.
  5. 제1항에 있어서, 서열번호 5-8로 이루어진 군으로부터 선택되는 아미노산 서열을 포함하는, 폴리펩타이드.
  6. 제1항에 있어서, 서열번호 1 및 5로 이루어진 군으로부터 선택되는 아미노산 서열을 포함하는, 폴리펩타이드.
  7. 제1항에 있어서, 서열번호 1의 아미노산 서열을 포함하는, 폴리펩타이드.
  8. 제1항에 있어서, 서열번호 5의 아미노산 서열을 포함하는, 폴리펩타이드.
  9. 제1항 내지 제8항 중 어느 한 항에 따른 폴리펩타이드를 여러개 포함하는 나노입자.
  10. 나노입자로서,
    (a) 각각의 제1 어셈블리가 동일한 제1 단백질을 여러개 포함하는, 복수의 제1 어셈블리; 및
    (b) 각각의 제2 어셈블리가 동일한 제2 단백질을 여러개로 포함하는, 복수의 제2 어셈블리를 포함하고,
    상기 제1 단백질의 아미노산 서열이 상기 제2 단백질의 서열과 상이하고,
    상기 복수의 제1 어셈블리가 상기 복수의 제2 어셈블리와 비-공유적으로 상호작용해 나노입자를 형성하며,
    상기 나노입자가 그 표면에 제2 단백질 하나 이상에 존재하는 SARS-CoV-2 항원 또는 이의 변이체 또는 상동체의 면역원성 부분을 나열하는, 나노입자.
  11. 제10항에 있어서, 상기 제2 단백질이 서열번호 85-124 또는 185-193로 이루어진 군으로부터 선택되는 아미노산 서열에 대해 적어도 95%, 적어도 96%, 적어도 97%, 적어도 98%, 적어도 99% 또는 적어도 100% 동일한 아미노산 서열을 포함하고, 제2 단백질 하나 이상에서 X1이 SARS-CoV-2 항원 또는 이의 변이체 또는 상동체의 면역원성 부분을 포함하고, X2는 생략되거나 또는 아미노산 링커이고, 괄호 안 잔기들은 선택적인, 나노입자.
  12. 제11항에 있어서, 상기 제2 단백질이 서열번호 85-88로 이루어진 군으로부터 선택되는 아미노산 서열을 포함하는, 나노입자.
  13. 제11항에 있어서, 상기 제2 단백질이 서열번호 85-86으로 이루어진 군으로부터 선택되는 아미노산 서열을 포함하는, 나노입자.
  14. 제11항에 있어서, 상기 제2 단백질이 서열번호 85의 아미노산 서열을 포함하는, 나노입자.
  15. 제11항 내지 제14항 중 어느 한 항에 있어서, 상기 제2 단백질들 중 적어도 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% 또는 100%는 X1이 SARS-CoV-2 또는 이의 변이체 또는 상동체로부터 유래한 스파이크 (S) 단백질 세포외 도메인 (ECD) 아미노산 서열, S1 서브유닛 아미노산 서열, S2 서브유닛 아미노산 서열, S1 수용체 결합 도메인 (RBD) 아미노산 서열, 및/또는 N-말단 도메인 (NTD) 아미노산 서열에 대해 적어도 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100%의 아미노산 서열 동일성을 가진 아미노산 서열을 포함하는, 나노입자.
  16. 제11항 내지 제15항 중 어느 한 항에 있어서, 상기 제2 단백질들 중 적어도 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% 또는 100%는 X1이 서열번호 125-137로 이루어진 군으로부터 선택되는 아미노산 서열에 대해 적어도 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100%의 아미노산 서열 동일성을 가진 아미노산 서열을 포함하는, 나노입자.
  17. 제11항 내지 제16항 중 어느 한 항에 있어서, 상기 제2 단백질들 중 적어도 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% 또는 100%는 X1이 서열번호 125의 아미노산 서열에 대해 적어도 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100%의 아미노산 서열 동일성을 가진 아미노산 서열을 포함하는, 나노입자.
  18. 제17항에 있어서,
    (a) 제2 단백질들 중 적어도 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% 또는 100%는 X1이, 하기 자연 생성 돌연변이 또는 돌연변이들의 조합 중 하나를 포함하는 돌연변이를 포함하지만 이로 제한되지 않는, K90N, K90T, G119S, Y126F, T151I, E157K, E157A, S167P, N174Y 및 L125R로 이루어진 군으로부터 선택되는 돌연변이를 서열번호 125를 기준으로 1, 2, 3, 4, 5, 6, 7 또는 모두 8개 위치에서 포함하거나:
    N174Y (UK 변이체);
    K90N/E157K/N174Y (남아프리카 변이체);
    K90N 또는 T/E157K/N174Y (브라질 변이체); 또는
    L125R (LA 변이체), 또는
    (b) 제2 단백질들 중 적어도 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% 또는 100%는 X1이, 하기 자연 생성 돌연변이 또는 돌연변이들의 조합 중 하나를 포함하는 돌연변이를 포함하지만 이로 제한되지 않는, L18F, T20N, P26S, 잔기 69-70의 결손, D80A, D138Y, R190S, D215G, K417N, K417T, G446S, L452R, Y453F, T478I, E484K, S494P, N501Y, A570D, D614G, H655Y, P681H, A701V, T716L로 이루어진 군으로부터 선택되는 돌연변이를 서열번호 130을 기준으로 1, 2, 3, 4, 5, 6, 7 또는 모두 8개 위치에서 포함하거나:
    N501Y, 선택적으로, 잔기 69-70의 결손, A570D, D614G, P681H 및/또는 T716L 중 1, 2, 3, 4 또는 5개를 추가로 포함함 (UK 변이체);
    K417N/E484K/N501Y, 선택적으로, L18F, D80A, D215G, D614G 및/또는 A701V 중 1, 2, 3, 4 또는 5개를 추가로 포함함 (남아프리카 변이체);
    K417N 또는 T/E484K/N501Y, 선택적으로, L18F, T20N, P26S, D138Y, R190S, D614G 및/또는 H655Y 중 1, 2, 3, 4 또는 5개를 추가로 포함함 (브라질 변이체); 또는
    L452R (LA 변이체).
  19. 제17항에 있어서, 상기 제2 단백질들 중 적어도 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% 또는 100%는 X1이 서열번호 125를 기준으로 K90N, K90T, E157K 및 N174Y로 이루어진 군으로부터 선택되는 돌연변이를 1, 2, 3 또는 모두 4종 포함하는, 나노입자.
  20. 제11항 내지 제19항 중 어느 한 항에 있어서, 상기 제2 단백질들 중 적어도 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% 또는 100%는 X1이 서열번호 125의 아미노산 서열을 포함하는, 나노입자.
  21. 제11항 내지 제20항 중 어느 한 항에 있어서, 상기 제2 단백질의 100%는 X1이 서열번호 125의 아미노산 서열을 포함하고, 제2 단백질들이 모두 동일한, 나노입자.
  22. 제10항 내지 제21항 중 어느 한 항에 있어서, 상기 복수의 제2 어셈블리가 총체적으로 2종, 3종, 4종, 5종, 6종, 7종, 8종 또는 그 보다 많은 종의 여러가지 SARS-CoV-2 항원들을 포함하는, 나노입자.
  23. 제10항 내지 제22항 중 어느 한 항에 있어서, 상기 복수의 제2 어셈블리가 제1항 내지 제8항 중 어느 한 항에 따른 폴리펩타이드의 아미노산 서열을 포함하는 폴리펩타이드를 총체적으로 2, 3, 4, 5, 6, 7, 8 또는 그 보다 많이 포함하는, 나노입자.
  24. 제10항 내지 제23항 중 어느 한 항에 있어서, 상기 제2 어셈블리들 모두 제1항 내지 제8항 중 어느 한 항에 따른 폴리펩타이드의 아미노산 서열을 포함하는 하나 이상의 제2 단백질을 포함하는, 나노입자.
  25. 제10항 내지 제24항 중 어느 한 항에 있어서, 상기 제2 단백질 모두 제1항 내지 제8항 중 어느 한 항에 따른 폴리펩타이드의 아미노산 서열을 포함하는, 나노입자.
  26. 제10항 내지 제25항 중 어느 한 항에 있어서, 상기 제1 단백질이 서열번호 152-159로 이루어진 군으로부터 선택되는 아미노산 서열에 대해 적어도 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100% 동일한 아미노산 서열을 포함하고, 괄호 안 서열이 선택적이며 존재할 수 있거나 또는 선택 잔기들 중 일부 또는 전부 생략될 수 있는, 나노입자.
  27. 제10항 내지 제26항 중 어느 한 항에 있어서, 상기 제1 단백질이 서열번호 152-159로 이루어진 군으로부터 선택되는 아미노산 서열에 대해 적어도 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100% 동일한 아미노산 서열을 포함하는, 나노입자.
  28. 제10항 내지 제27항 중 어느 한 항에 있어서, 상기 제1 단백질이 서열번호 155의 아미노산 서열을 포함하는, 나노입자.
  29. 제28항에 있어서, 상기 제2 어셈블리 하나 이상이 서열번호 85-88로 이루어진 군으로부터 선택되는 아미노산 서열을 포함하는 제2 단백질을 하나 이상 포함하는, 나노입자.
  30. 제28항에 있어서, 상기 제2 어셈블리들 모두 서열번호 85-88로 이루어진 군으로부터 선택되는 아미노산 서열을 포함하는 제2 단백질을 하나 이상 포함하는, 나노입자.
  31. 제28항에 있어서, 상기 제2 단백질 모두 서열번호 85-88로 이루어진 군으로부터 선택되는 아미노산 서열을 포함하는, 나노입자.
  32. 제10항 내지 제31항 중 어느 한 항에 있어서, 상기 제1 어셈블리가 각각 오량체이고, 상기 제2 어셈블리가 각각 삼량체인, 나노입자.
  33. 제10항 내지 제32항 중 어느 한 항에 있어서,
    (a) 상기 제1 단백질이 서열번호 155의 아미노산 서열을 포함하고,
    (b) 상기 제2 단백질 모두 서열번호 85의 아미노산 서열을 포함하며,
    상기 제2 단백질들 중 적어도 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% 또는 100%는 X1이 서열번호 125의 아미노산 서열에 대해 적어도 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100%의 아미노산 서열 동일성을 가진 아미노산 서열을 포함하는, 나노입자.
  34. 제10항 내지 제33항 중 어느 한 항에 있어서,
    (a) 상기 제1 단백질이 서열번호 155의 아미노산 서열을 포함하고,
    (b) 상기 제2 단백질 모두 서열번호 85의 아미노산 서열을 포함하며,
    상기 제2 단백질들 중 적어도 적어도 50%, 60%, 70%, 80%, 90% 또는 100%는 X1이 서열번호 125의 아미노산 서열에 대해 적어도 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100%의 아미노산 서열 동일성을 가진 아미노산 서열을 포함하는, 나노입자.
  35. 제10항 내지 제34항 중 어느 한 항에 있어서,
    (a) 상기 제1 단백질이 서열번호 155의 아미노산 서열을 포함하고,
    (b) 상기 제2 단백질 모두 서열번호 1-8로 이루어진 군으로부터 선택되는 아미노산 서열을 포함하는, 나노입자.
  36. 제10항 내지 제35항 중 어느 한 항에 있어서,
    (a) 상기 제1 단백질이 서열번호 155의 아미노산 서열을 포함하고,
    (b) 상기 제2 단백질 모두 서열번호 1 또는 5로 이루어진 군으로부터 선택되는 아미노산 서열을 포함하는, 나노입자.
  37. 제10항 내지 제36항 중 어느 한 항에 따른, 바람직하게는 제33항 내지 제36항 중 어느 한 항에 따른 복수의 나노입자를 포함하는 조성물.
  38. 제1항 내지 제8항 중 어느 한 항에 따른 폴리펩타이드를, 바람직하게는 서열번호 1-12의 아미노산 서열을 암호화하는, 핵산 분자.
  39. 제42항에 있어서, 상기 폴리뉴클레오티드가 mRNA를 포함하는, 핵산 분자.
  40. 적절한 조절 서열에 작동가능하게 연결된 제38항 또는 제39항에 따른 핵산 분자를 포함하는 발현 벡터.
  41. 제1항 내지 제40항 중 어느 한 항에 따른 폴리펩타이드, 나노입자, 조성물, 핵산 및/또는 발현 벡터를 포함하는 세포.
  42. 하기 성분을 포함하는 약학적 조성물:
    (a) 제1항 내지 제41항 중 어느 한 항에 따른 폴리펩타이드, 나노입자, 조성물, 핵산, 발현 벡터 및/또는 세포; 및
    (b) 약제학적으로 허용가능한 담체.
  43. 제46항에 있어서, 제33항 내지 제36항 중 어느 한 항에 따른 복수의 나노입자를 포함하는, 약학적 조성물.
  44. 제37항, 제42항 또는 제43항에 있어서, 보강제를 더 포함하는, 조성물 또는 약학적 조성물.
  45. 제1항 내지 제37항 중 어느 한 항에 따른 폴리펩타이드, 나노입자, 조성물, 핵산 및/또는 조성물을 포함하는, 백신.
  46. 제45항에 있어서, 제33항 내지 제36항 중 어느 한 항에 따른 복수의 나노입자를 포함하는, 백신.
  47. SARS-CoV-2 감염을 치료하거나 또는 SARS-CoV-2 감염의 진행을 제한하기 위한 방법으로서, 필요한 개체에, 제1항 내지 제46항 중 어느 한 항에 따른 폴리펩타이드, 나노입자, 조성물, 핵산, 약학적 조성물 또는 백신을, 감염을 치료하거나 또는 감염의 진행을 제한하는데 유효한 양으로 투여하는 것을 포함하는, 방법.
  48. 제47항에 있어서, 제33항 내지 제36항 중 어느 한 항에 따른 복수의 나노입자, 제43항의 약학적 조성물 또는 제46항의 백신을 개체에 투여하는 것을 포함하는, 방법.
  49. 제47항 또는 제48항에 있어서, 상기 개체는 SARS-CoV-2로 감염되지 않은 개체이고, 상기 투여가 개체에서 SARS-CoV-2 감염의 진행을 제한하는 면역 반응을 상기 개체에서 SARS-CoV-2에 대항하여 유발하는, 방법.
  50. 제49항에 있어서, 상기 투여가 제1 용량 및 제2 용량의 투여를 포함하고, 제1 용량을 투여한 후 약 2주 내지 약 12주 또는 약 4주 내지 약 12주 경과 시점에 제2 용량을 투여하는, 방법.
  51. 제50항에 있어서, 상기 투여가
    (a) 서열번호 125-137의 아미노산 서열에 대해 적어도 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100%의 아미노산 서열 동일성을 가진 아미노산 서열을 암호화하는 DNA, mRNA 또는 아데노바이러스 벡터 백신을, 개체에게 감작 용량으로 투여하고; 및
    (b) 개체에, 제1항 내지 제46항 중 어느 한 항에 따른 폴리펩타이드, 나노입자, 조성물, 핵산, 약학적 조성물 또는 백신을 부스트 용량으로 투여하는 것을 포함하는, 방법.
  52. 제50항에 있어서, 상기 투여가
    (a) 개체에 제1항 내지 제46항 중 어느 한 항에 따른 폴리펩타이드, 나노입자, 조성물, 핵산, 약학적 조성물 또는 백신의 감작 용량으로 투여하고; 및
    (b) 개체에, 서열번호 125-137의 아미노산 서열에 대해 적어도 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100%의 아미노산 서열 동일성을 가진 아미노산 서열을 암호화하는 DNA, mRNA 또는 아데노바이러스 벡터 백신을, 부스트 용량으로 투여하는 것을 포함하는, 방법.
  53. 제47항 내지 제52항 중 어느 한 항에 있어서, 상기 면역 반응이 SARS-CoV-2에 대항하는 중화 항체을 생성하는 것을 포함하는, 방법.
  54. 제47항 내지 제53항 중 어느 한 항에 있어서, 상기 면역 반응이 SARS-CoV-2 스파이크 단백질에 대한 항체-특이적인 반응을 기하 평균 역가 적어도 1 x 105으로 유발하는 것을 포함하는, 방법.
  55. 제47항, 제48항, 제53항 또는 제54항 중 어느 한 항에 있어서, 상기 개체는 SARS-CoV-2를 포함하지만 이로 제한되지 않는 중증 급성 호흡기 (SARS) 바이러스에 의해 감염된 개체이고, 상기 투여가 개체에서 SARS 바이러스 감염을 치료하는 면역 반응을 상기 개체에서 SARS 바이러스에 대항하여 유발하는, 방법.
  56. 하기를 포함하는 키트:
    (a) 제1항 내지 제8항 중 어느 한 항에 따른 폴리펩타이드, 바람직하게는 서열번호 1 또는 5의 아미노산 서열을 포함하는 폴리펩타이드; 및
    (b) 서열번호 152-159로 이루어진 군으로부터 선택되는 아미노산 서열에 대해 적어도 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100% 동일한 아미노산 서열을 포함하는 제1 단백질로서, 괄호 안 서열이 선택적이고 존재하거나 또는 존재하지 않을 수 있으며, 바람직하게는 제1 단백질이 서열번호 155의 아미노산 서열을 포함하는, 제1 단백질.
  57. 하기를 포함하는 키트:
    (a) 제1항 내지 제8항 중 어느 한 항에 따른 폴리펩타이드를 암호화하는 핵산, 바람직하게는 서열번호 1 또는 5의 아미노산 서열을 포함하는 폴리펩타이드를 암호화하는 핵산; 및
    (b) 서열번호 152-159로 이루어진 군으로부터 선택되는 아미노산 서열에 대해 적어도 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100% 동일한 아미노산 서열을 포함하는 제1 단백질을 암호화하는 핵산으로서, 괄호 안 서열이 선택적이고 존재하거나 또는 존재하지 않을 수 있으며, 바람직하게는 제1 단백질이 서열번호 155의 아미노산 서열을 포함하는, 핵산.
  58. 하기를 포함하는 키트:
    (a) 적절한 조절 서열에 작동가능하게 연결된, 제1항 내지 제8항 중 어느 한 항에 따른 폴리펩타이드를 암호화하는 핵산을 포함하는, 발현 벡터로서, 상기 폴리펩타이드가 서열번호 1 또는 5의 아미노산 서열을 포함하는, 발현 벡터; 및
    (b) 서열번호 152-159로 이루어진 군으로부터 선택되는 아미노산 서열에 대해 적어도 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100% 동일한 아미노산 서열을 포함하는 제1 단백질을 암호화하는 핵산을 포함하는 발현 벡터로서, 괄호 안 서열이 선택적이며 존재하거나 또는 존재하지 않을 수 있으며, 상기 핵산이 적절한 조절 서열에 작동가능하게 연결되고, 바람직하게는 상기 제1 단백질이 서열번호 155의 아미노산 서열을 포함하는, 발현 벡터.
  59. 하기를 포함하는 키트:
    (a) 발현 벡터를 포함하는 세포로서, 상기 발현 벡터가 적절한 조절 서열에 작동가능하게 연결된, 제1항 내지 제8항 중 어느 한 항에 따른 폴리펩타이드를 암호화하는 핵산을 포함하며, 바람직하게는 상기 폴리펩타이드가 서열번호 1 또는 5의 아미노산 서열을 포함하는, 세포; 및
    (b) 발현 벡터를 포함하는 세포로서, 상기 발현 벡터가 서열번호 152-159로 이루어진 군으로부터 선택되는 아미노산 서열에 대해 적어도 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% 또는 100% 동일한 아미노산 서열을 포함하는 제1 단백질을 암호화하는 핵산을 포함하며, 괄호 안 서열이 선택적이며 존재하거나 또는 존재하지 않을 수 있으며, 상기 핵산이 적절한 조절 서열에 작동가능하게 연결되고, 바람직하게는 상기 제1 단백질이 서열번호 155의 아미노산 서열을 포함하는, 세포.
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