KR20170124565A - 변경된 PAM 특이성을 갖는 조작된 CRISPR-Cas9 뉴클레아제 - Google Patents

변경된 PAM 특이성을 갖는 조작된 CRISPR-Cas9 뉴클레아제 Download PDF

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KR20170124565A
KR20170124565A KR1020177026620A KR20177026620A KR20170124565A KR 20170124565 A KR20170124565 A KR 20170124565A KR 1020177026620 A KR1020177026620 A KR 1020177026620A KR 20177026620 A KR20177026620 A KR 20177026620A KR 20170124565 A KR20170124565 A KR 20170124565A
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제이. 키쓰 종
벤자민 클레인스티버
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Abstract

변경된 및 개선된 PAM 특이성을 갖는 조작된 CRISPR-Cas9 뉴클레아제, 및 게놈 공학, 에피게놈 공학 및 게놈 표적화에서의 그의 용도가 개시된다.

Description

변경된 PAM 특이성을 갖는 조작된 CRISPR-Cas9 뉴클레아제
우선권 주장
본 출원은 2015년 3월 3일에 출원된 미국 가특허 출원 일련 번호 61/127,634; 2015년 5월 22일에 출원된 62/165,517; 2015년 10월 9일에 출원된 62/239,737; 및 2015년 11월 20일에 출원된 62/258,402를 우선권으로 주장한다. 상기 문헌의 전체 내용은 본원에 참고로 포함된다.
연방정부 지원받은 연구 또는 개발
본 발명은 국립보건원에 의해 수여된 승인 번호 DP1 GM105378, NIH R01 GM107427, 및 R01 GM088040 하에 정부 지원을 받아 이루어졌다. 정부는 본 발명에 대해 특정한 권리를 갖는다.
기술 분야
적어도 부분적으로 본 발명은 변경된 및 개선된 프로토스페이서 인접 모티프 (Protospacer Adjacent Motif, PAM) 특이성을 갖는 조작된 주기적으로 간격을 띄고 분포하는 짧은 회문구조 반복부 (Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR)/CRISPR-연관된 단백질 9 (Cas9) 뉴클레아제, 및 게놈 공학, 에피게놈 공학 및 게놈 표적화에서 그의 용도에 관한 것이다.
CRISPR-Cas9 뉴클레아제는 광범위한 유기체 및 세포 유형에서 효율적인 맞춤형 게놈 편집을 가능하게 한다 (Sander & Joung, Nat Biotechnol 32, 347-355 (2014); Hsuet al., Cell 157, 1262-1278 (2014); Doudna & Charpentier, Science 346, 1258096 (2014); Barrangou & May, Expert Opin Biol Ther 15, 311-314 (2015)). Cas9에 의한 표적 부위 인식은 crRNA 및 tracrRNA로 공지된 2가지 짧은 RNA에 의해 지시되고 (Deltcheva et al., Nature 471, 602-607 (2011); Jinek et al., Science 337, 816-821 (2012)), 이들은 키메라 단일 가이드 RNA (sgRNA)에 융합될 수 있다 (Jinek et al., Science 337, 816-821 (2012); Jinek et al., Elife 2, e00471 (2013); Mali et al., Science 339, 823-826 (2013); Cong et al., Science 339, 819-823 (2013)). (crRNA로부터 유래된) sgRNA의 5' 말단은 표적 DNA 부위와 염기쌍을 형성할 수 있고, 이로써 Cas9/sgRNA 복합체에 의한 부위-특이적 분할의 직접적인 재프로그래밍화를 허용한다 (Jinek et al., Science 337, 816-821 (2012)). 그러나, Cas9는 또한 sgRNA와 염기쌍을 형성하는 DNA에 근접하여 있는 특이적 프로토스페이서 인접 모티프 (PAM)를 인식하여야 하고 (Mojica et al., Microbiology 155, 733-740 (2009); Shah et al., RNA Biol 10, 891-899 (2013); Jinek et al., Science 337, 816-821 (2012); Sapranauskas et al., Nucleic Acids Res 39, 9275-9282 (2011); Horvath et al., J Bacteriol 190, 1401-1412 (2008)), 이는 서열-특이적 인식을 개시하는데 필요한 요건이지만 (Sternberg et al., Nature 507, 62-67 (2014)), 또한 게놈 편집을 위한 이들 뉴클레아제의 표적화 범위를 제한할 수 있다. 광범위하게 사용되는 스트렙토코쿠스 피오게네스 Cas9 (SpCas9)는 무작위 DNA 서열의 8 bp마다 한 번 발생하는 짧은 NGG PAM을 인식한다 (Jinek et al., Science 337, 816-821 (2012); Jiang et al., Nat Biotechnol 31, 233-239 (2013)). 대조적으로, 지금까지 특성분석된 다른 Cas9 이종상동유전자(orthologue)는 더 긴 PAM을 인식할 수 있다 (Horvath et al., J Bacteriol 190, 1401-1412 (2008); Fonfara et al., Nucleic Acids Res 42, 2577-2590 (2014); Esvelt et al., Nat Methods 10, 1116-1121 (2013); Ran et al., Nature 520, 186-191 (2015); Zhang et al., Mol Cell 50, 488-503 (2013)). 예를 들어, 바이러스 전달에 더욱 적합한 몇몇 작은 Cas9 이종상동유전자 중 하나인 스타필로코쿠스 아우레우스(Staphylococcus aureus) Cas9 (SaCas9) (Horvath et al., J Bacteriol 190, 1401-1412 (2008); Ran et al., Nature 520, 186-191 (2015); Zhang et al., Mol Cell 50, 488-503 (2013))는 무작위 DNA의 32 bp마다 한 번 발생하는 것으로 예상되는 더 긴 NNGRRT (서열식별번호(SEQ ID NO):46) PAM을 인식한다. 작은 유전자 요소의 변형 (예를 들어, 전사 인자 결합 부위 (Canver et al. Nature.;527(7577):192-7 (2015); Vierstra et al., Nat Methods. 12(10):927-30 (2015)) 또는 PAM 내에서 서열 차이를 위치시킴으로써 대립유전자-특이적 변경의 수행 (Courtney, D.G. et al. Gene Ther. 23(1):108-12 (2015)을 비롯한 다양한 적용을 위해 Cas9 이종상동유전자의 표적화 범위를 넓히는 것이 중요하다.
본원에 기재된 바와 같이, 흔히 사용되는 스트렙토코쿠스 피오게네스(Streptococcus pyogenes) Cas9 (SpCas9) 뿐만 아니라 스타필로코쿠스 아우레우스 Cas9 (SaCas9)는 구조적 정보, 박테리아 선택-기반으로 지시된 진화, 및 조합 고안을 이용하여 신규한 PAM 서열을 인식하도록 조작되었다. 이들 변경된 PAM 특이성 변이체는 야생형 SpCas9 또는 SaCas9에 의해 효율적으로 표적화될 수 없는 제브라피쉬 및 인간 세포에서의 내인성 유전자 부위의 강력한 편집을 가능하게 한다. 또한, 본 발명자들은 비-표준적인(non-canonical) NAG 및 NGA PAM을 갖는 부위에 대해 감소된 활성을 갖는, 인간 세포에서 개선된 PAM 특이성을 나타내는 또다른 SpCas9 변이체를 확인하고 특성분석하였다. 또한, 본 발명자들은 완전히 상이한 PAM 특이성을 갖는 2가지 소형 Cas9 이종상동유전자인 스트렙토코쿠스 써모필루스(Streptococcus thermophilus) Cas9 (St1Cas9) 및 스타필로코쿠스 아우레우스 Cas9 (SaCas9)가 본 발명자들의 박테리아 선택 시스템에서 및 인간 세포에서 효율적으로 기능하였음을 발견하였고, 이는 본 발명자들의 조작 전략이 다른 종으로부터의 Cas9로 확장될 수 있음을 시사한다. 본 발명자들의 발견은 광범위하게 유용한 SpCas9 및 SaCas9 변이체를 제공하며, 이들은 본원에서 집합적으로 "변이체" 또는 "상기 변이체"로 지칭된다.
제1 측면에서, 본 발명은 하기 위치: G1104, S1109, L1111, D1135, S1136, G1218, N1317, R1335, T1337 중 하나 이상에서 돌연변이를 갖는, 예를 들어 서열식별번호:1의 아미노산 서열과 적어도 80% 동일한 서열을 포함하는, 단리된 스트렙토코쿠스 피오게네스 Cas9 (SpCas9) 단백질을 제공한다. 일부 실시양태에서, 변이체 SpCas9 단백질은 하기 돌연변이: G1104K; S1109T; L1111H; D1135V; D1135E; D1135N; D1135Y; S1136N; G1218R; N1317K; R1335E; R1335Q 및 T1337R 중 하나 이상을 포함한다. 일부 실시양태에서, 변이체 SpCas9 단백질은 하기 돌연변이: D1135; D1135V/R1335Q/T1337R (VQR 변이체); D1135E/R1335Q/T1337R (EQR 변이체); D1135V/G1218/R1335Q/T1337R (VRQR 변이체); D1135N/G1218R/R1335Q/T1337R (NRQR 변이체); D1135Y/G1218R/R1335Q/T1337R (YRQR 변이체); G1104K/D1135V/G1218R/R1335Q/T1337R (KVRQR 변이체); S1109T/D1135V/G1218R/R1335Q/T1337R (TVRQR 변이체); L1111H/D1135V/G1218R/R1335Q/T1337R (HVRQR 변이체); D1135V/S1136N/G1218R/R1335Q/T1337R (VNRQR 변이체); D1135V/G1218R/N1317K/R1335Q/T1337R (VRKQR 변이체); 또는 D1135V/G1218R/R1335E/T1337R (VRER 변이체)를 포함한다.
일부 실시양태에서, 변이체 SpCas9 단백질은 D10, E762, D839, H983 또는 D986에서의 돌연변이; 및 H840 또는 N863에서의 돌연변이로 이루어진 군으로부터 선택된, 뉴클레아제 활성을 감소시키는 하나 이상의 돌연변이를 포함한다.
일부 실시양태에서, 돌연변이는 (i) D10A 또는 D10N, 및 (ii) H840A, H840N 또는 H840Y이다.
또한, 본원에는 하기 위치: E782, N968 및/또는 R1015 중 하나 이상에서 돌연변이를 갖는, 예를 들어 서열식별번호:2의 아미노산 서열과 적어도 80% 동일한 서열을 포함하는, 단리된 스타필로코쿠스 아우레우스 Cas9 (SaCas9) 단백질이 제공된다. 또한, 본원에는 하기 위치: E735, E782, K929, N968, A1021, K1044 및/또는 R1015 중 하나, 둘 또는 그 이상에서 돌연변이를 갖는, 단리된 스타필로코쿠스 아우레우스 Cas9 (SaCas9) 단백질이 제공된다. 일부 실시양태에서, 변이체 SaCas9 단백질은 하기 돌연변이: R1015Q, R1015H, E782K, N968K, E735K, K929R, A1021T, K1044N 중 하나 이상을 포함한다. 일부 실시양태에서, 변이체 SaCas9 단백질은 D10, D556, H557 및/또는 N580에서의 돌연변이로 이루어진 군으로부터 선택된, 뉴클레아제 활성을 감소시키는 하나 이상의 돌연변이를 포함한다.
일부 실시양태에서, 변이체 SaCas9 단백질은 D10A, D556A, H557A, N580A, 예를 들어 D10A/H557A 및/또는 D10A/D556A/H557A/N580A에서의 돌연변이를 포함한다.
본원에 기재된 SpCas9 변이체는 하기 위치: D1135, G1218, R1335, T1337 중 하나 이상에서 돌연변이를 갖는 서열식별번호:1의 아미노산 서열을 포함할 수 있다. 일부 실시양태에서, SpCas9 변이체는 하기 돌연변이: D1135V; D1135E; G1218R; R1335E; R1335Q 및 T1337R 중 하나 이상을 포함할 수 있다. 일부 실시양태에서, SpCas9 변이체는 하기 돌연변이 세트: D1135V/R1335Q/T1337R (VQR 변이체); D1135V/G1218R/R1335Q/T1337R (VRQR 변이체); D1135E/R1335Q/T1337R (EQR 변이체); 또는 D1135V/G1218R/R1335E/T1337R (VRER 변이체) 중 하나를 포함할 수 있다.
본원에 기재된 SaCas9 변이체는 하기 위치: E735, E782, K929, N968, R1015, A1021 및/또는 K1044 중 하나 이상에서 돌연변이를 갖는 서열식별번호:2의 아미노산 서열을 포함할 수 있다. 일부 실시양태에서, SaCas9 변이체는 하기 돌연변이: R1015Q, R1015H, E782K, N968K, E735K, K929R, A1021T, K1044N 중 하나 이상을 포함할 수 있다. 일부 실시양태에서, SaCas9 변이체는 하기 돌연변이 세트: E782K/N968K/R1015H (KKH 변이체); E782K/K929R/R1015H (KRH 변이체); 또는 E782K/K929R/N968K/R1015H (KRKH 변이체) 중 하나를 포함할 수 있다.
또한, 본원에서 임의적인 개재 링커로 이종 기능적 도메인에 융합된 본원에 기재된 단리된 변이체 SaCas9 또는 SpCas9 단백질을 포함하는 융합 단백질이며, 여기서 링커는 융합 단백질의 활성을 방해하지 않는 것인 융합 단백질을 제공한다. 일부 실시양태에서, 이종 기능적 도메인은 전사 활성화 도메인이다. 일부 실시양태에서, 전사 활성화 도메인은 VP64 또는 NF-κB p65로부터의 것이다. 일부 실시양태에서, 이종 기능적 도메인은 전사 사일런서 또는 전사 저해 도메인이다. 일부 실시양태에서, 전사 저해 도메인은 크뤼펠-연관된 박스 (KRAB) 도메인, ERF 저해인자 도메인 (ERD), 또는 mSin3A 상호작용 도메인 (SID)이다. 일부 실시양태에서, 전사 사일런서는 이질염색질 단백질 1 (HP1), 예를 들어 HP1α 또는 HP1β이다. 일부 실시양태에서, 이종 기능적 도메인은 DNA의 메틸화 상태를 변형시키는 효소이다. 일부 실시양태에서, DNA의 메틸화 상태를 변형시키는 효소는 DNA 메틸트랜스퍼라제 (DNMT) 또는 TET 단백질이다. 일부 실시양태에서, TET 단백질은 TET1이다. 일부 실시양태에서, 이종 기능적 도메인은 히스톤 서브유닛을 변형시키는 효소이다. 일부 실시양태에서, 히스톤 서브유닛을 변형시키는 효소는 히스톤 아세틸트랜스퍼라제 (HAT), 히스톤 데아세틸라제 (HDAC), 히스톤 메틸트랜스퍼라제 (HMT), 또는 히스톤 데메틸라제이다. 일부 실시양태에서, 이종 기능적 도메인은 생물학적 테더이다. 일부 실시양태에서, 생물학적 테더는 MS2, Csy4 또는 람다 N 단백질이다. 일부 실시양태에서, 이종 기능적 도메인은 FokI이다.
또한, 본원에는 본원에 기재된 변이체 SaCas9 또는 SpCas9 단백질을 코딩하는 단리된 핵산, 뿐만 아니라 본원에 기재된 변이체 SaCas9 또는 SpCas9 단백질을 발현시키기 위해 임의적으로 하나 이상의 조절 도메인에 작동가능하게 연결된 단리된 핵산을 포함하는 벡터가 제공된다. 또한, 본원에는 본원에 기재된 핵산을 포함하고, 임의적으로 본원에 기재된 변이체 SaCas9 또는 SpCas9 단백질을 발현하는 숙주 세포, 예를 들어 포유동물 숙주 세포가 제공된다.
또한, 본원에는 본원에 기재된 단리된 변이체 SaCas9 또는 SpCas9 단백질, 및 세포의 게놈의 선택된 부분에 상보적인 영역을 갖는 가이드 RNA를 세포에서 발현시킴으로써 세포의 게놈을 변경시키는 방법이 제공된다.
또한, 본원에는 변이체 단백질, 및 세포의 게놈의 선택된 부분에 상보적인 영역을 갖는 가이드 RNA를 세포에서 발현시킴으로써 세포의 게놈을 변경시키는, 예를 들어 선택적으로 변경시키는 방법이 제공된다.
또한, 본원에 기재된 단백질 변이체, 및 세포의 게놈의 선택된 부분에 상보적인 영역을 갖는 가이드 RNA를 세포와 접촉시킴으로써 세포의 게놈을 변경시키는, 예를 들어 선택적으로 변경시키는 방법이 제공된다.
일부 실시양태에서, 단리된 단백질 또는 융합 단백질은 핵 국재화 서열, 세포 침투 펩티드 서열 및/또는 친화성 태그 중 하나 이상을 포함한다.
본원에 기재된 방법의 일부 실시양태에서, 세포는 줄기 세포, 예를 들어 배아 줄기 세포, 중간엽 줄기 세포, 또는 유도된 만능 줄기 세포이거나; 살아있는 동물에 있거나; 또는 배아, 예를 들어 포유동물, 곤충 또는 어류 (예를 들어, 제브라피쉬) 배아 또는 배아 세포에 있다.
추가로, 본원에는 이중 가닥 DNA (dsDNA) 분자를 변경시키는 방법, 예를 들어 시험관내 방법이 제공된다. 상기 방법은 본원에 기재된 하나 이상의 변이체 단백질, 및 dsDNA 분자의 선택된 부분에 상보적인 영역을 갖는 가이드 RNA를 dsDNA 분자와 접촉시키는 것을 포함한다.
달리 정의되지 않는다면, 모든 기술적 및 과학적 용어는 본 발명이 속한 기술분야의 기술자에 의해 통상적으로 이해되는 것과 동일한 의미를 갖는다. 본 발명에서 이용되는 방법 및 물질이 본원에 기재되고, 관련 기술분야에 공지된 다른 적합한 방법 및 물질 또한 이용될 수 있다. 상기 물질, 방법 및 실시예는 단지 예시적인 것이고, 제한되는 것으로 의도되지 않는다. 본원에 언급된 모든 공보, 특허 출원, 특허, 서열, 데이터베이스 항목, 및 다른 참고문헌은 그들의 전문이 참고로 포함된다. 분쟁의 여지가 있는 경우, 정의를 비롯한 본 명세서가 우선일 것이다.
본 발명의 다른 특성 및 이점은 하기 상세한 설명, 도면 및 청구항으로부터 자명할 것이다.
본 특허 또는 출원 파일은 적어도 하나의 컬러 도면을 포함한다. 컬러 도면(들)을 갖는 이 특허 또는 특허 출원 공보의 사본은 요청시 필요한 수수료를 지불하여 특허청에 제공될 것이다.
도 1A-J | 변경된 PAM 특이성을 갖는 SpCas9 변이체의 진화 및 특성분석. a, PAM 염기로 염기-특이적 접촉을 하게 하는 SpCas9 잔기의 합리적인 돌연변이는 U2OS 인간 세포-기재의 강화된 녹색 형광 단백질 (EGFP) 파괴 검정에서 PAM 특이성을 변경시키기에는 불충분하다. 파괴 빈도를 유세포 분석법에 의해 정량화하고, 이번 및 후속 패널 (c, g, h, 및 j)에서 백그라운드 대조군에서 관찰된 파괴의 평균 수준은 적색 점선으로 나타내고, 오차 막대는 s.e.m., n = 3을 나타낸다. b, SpCas9의 PAM 특이성을 변경시키기 위해 사용된 2-플라스미드 양성 선택 검정의 개략도. 기능적 Cas9/sgRNA 복합체에 의한 양성 선택 플라스미드 내에서 표적 부위의 분할은 박테리아를 선택적 배지에 두었을 때 생존을 위해 필요하다 (도 12A-B 또한 참고). c, NGA PAM을 함유하는 표적 부위를 분할할 수 있는 SpCas9 변이체에 대한 양성 선택으로부터 수득한 돌연변이의 조합 조립 및 시험. SpCas9 변이체를 NGG 또는 NGA PAM을 함유하는 부위를 표적화하는 sgRNA와 쌍형성시키고, EGFP 파괴 검정을 이용하여 활성을 평가하였다. 오차 막대는 s.e.m., n = 3을 나타낸다. d, 박테리아를 선택적 배지에 두었을 때 선택 플라스미드의 분할에 의해 세포 사멸이 일어나는, 음성 선택 검정의 개략도. 이 시스템은 프로토스페이서의 3' 말단에 인접한 무작위화된 서열을 함유하는 플라스미드의 라이브러리를 생성함으로써 Cas9의 PAM 특이성을 프로파일링하도록 조정되었다 (도 13b 또한 참고). e, 야생형 SpCas9의 선택후 PAM 고갈 값 (PPDV)과 2가지 무작위화된 PAM 라이브러리 (각각 상이한 프로토스페이서를 가짐)의 산점도. PAM을 그들의 제2/제3/제4 위치에 의해 분류하여 플롯팅하였다. 적색 점선은 통계적으로 유의한 고갈에 대한 컷오프를 나타내고 (dCas9 대조군 실험으로부터 수득함, 도 13c 참고), 회색 점선은 5배 고갈 (0.2의 PPDV)을 나타낸다. f, 야생형 SpCas9에 의해 인식되는 것과 구별되는 PAM을 인식하는 VQR 및 EQR SpCas9 변이체에 대한 PPDV 산점도. g, NGAN 및 NGNG PAM을 갖는 부위에 대한 야생형, VQR 및 EQR SpCas9의 EGFP 파괴 빈도. 오차 막대는 s.e.m., n = 3을 나타낸다. h, NGCG PAM을 함유하는 표적 부위를 분할할 수 있는 SpCas9 변이체에 대한 양성 선택으로부터 수득된 돌연변이의 조합 조립 및 시험. NGGG 또는 NGCG PAM을 함유하는 부위를 표적화하는 sgRNA를 EGFP 파괴 검정을 이용하여 Cas9 표적화에 대해 평가하였다. 오차 막대는 s.e.m., n = 3을 나타낸다. i, VRER 변이체에 대한 PPDV 산점도. j, NGCN 및 NGNG PAM을 갖는 부위에 대한 야생형 및 VRER SpCas9의 EGFP 파괴 빈도. 오차 막대는 s.e.m., n = 3을 나타낸다.
도 2 | 진화된 PAM 특이성을 갖는 SpCas9 변이체는 제브라피쉬 배아 및 인간 세포에서 내인성 부위를 강력하게 변형시킨다. a, NGAG PAM을 보유한 내인성 유전자 부위에 대해 야생형 또는 VQR SpCas9에 의해 유도된 제브라피쉬 배아에서의 돌연변이 유발 빈도의 정량화. 돌연변이 빈도는 T7E1 검정을 이용하여 결정하였고, 오차 막대는 s.e.m., n = 5 내지 9개의 개별 배아를 나타낸다. b, NGAG, NGAT 및 NGAA PAM을 함유하는 부위로 표적화된 sgRNA를 갖는 4가지 내인성 인간 유전자에 있는 16개의 표적 부위에서 T7E1 검정에 의해 정량화된 VQR 변이체의 돌연변이 빈도. 오차 막대는 s.e.m., n = 3을 나타낸다. c, NGA PAM을 갖는 내인성 인간 유전자 표적 부위에 대한 야생형 SpCas9의 돌연변이 빈도. 비교의 편의를 위해, 동일한 sgRNA를 이용하는 VQR 변이체에 대한 돌연변이 빈도를 여기에 다시 제시하였다 (패널 b에 제시된 것과 동일한 데이터). 오차 막대는 s.e.m., n = 3을 나타내고, n.d.는 T7E1에 의해 검출불가능함이다. d, T7E1 검정에 의해 정량화된 3가지 내인성 인간 유전자에 있는 NGCG PAM을 함유하는 9개의 표적 부위에서 야생형, VRER 및 VQR SpCas9의 돌연변이 빈도. 19 및 20 nt의 sgRNA 상보성 길이를 이용하였고, 오차 막대는 s.e.m., n = 3을 나타낸다. e, 인간 게놈에서 야생형, VQR 및 VRER SpCas9에 의해 표적화가능한 20 nt 스페이서를 갖는 부위 개수의 표시. f, 패널 b 및 d로부터의 sgRNA를 이용하여 VQR 및 VRER SpCas9 변이체에 대해 GUIDE-seq에 의해 확인된 오프-타겟(off-target) 분할 부위의 개수.
도 3 | D1135E 돌연변이는 SpCas9의 PAM 인식 및 스페이서 특이성을 개선시 킨다. a, 2가지 무작위화된 PAM 라이브러리에 대한 야생형 및 D1135E SpCas9의 PPDV 산점도 (각각 좌측 및 우측 패널). PAM을 그들의 제2/제3/제4 위치에 의해 분류하여 플롯팅하였다. 야생형 SpCas9에 대해 제시된 데이터는 도 1d의 플롯과 동일하고, 편의를 위해 여기에 다시 제시하였다. 적색 점선은 통계적으로 유의하게 고갈된 PAM을 나타내고 (도 13c 참고), 회색 점선은 5배 고갈 컷오프 (0.2의 PPDV)를 나타낸다. b, 인간 세포에서 NGG, NAG 및 NGA PAM을 함유하는 부위에 대한 야생형 및 D1135E SpCas9의 EGFP 파괴 활성. 파괴 빈도를 유세포 분석법에 의해 정량화하고, 이 패널 및 (d)에서는 백그라운드 대조군에 의해 관찰된 파괴의 평균 수준을 적색 점선으로 나타내었고, 오차 막대는 s.e.m., n = 3을 나타내고, 활성에서의 평균 배수 변화를 제시하였다. c, 인간 세포에 있는 6개의 내인성 부위에서 야생형 및 D1135E SpCas9에 대해 T7E1에 의해 검출된 돌연변이 유발 빈도. 오차 막대는 s.e.m., n = 3을 나타내고, 활성에서의 평균 배수 변화를 제시하였다. d, 인간 세포에서 EGFP 파괴 실험을 위해 형질감염된 야생형 또는 D1135E SpCas9-코딩 플라스미드의 양의 적정. 이들 모든 실험에서 사용된 sgRNA 플라스미드의 양은 250 ng로 고정되었다. 상이한 EGFP 부위를 표적화하는 2가지 sgRNA를 사용하였고, 오차 막대는 s.e.m., n = 3을 나타낸다. e, 야생형 및 D1135E SpCas9를 이용하여 3가지 sgRNA에 대한 온- 및 오프-타겟 부위의 표적화된 심층-시퀀싱. 온-타겟(on-target) 부위는 상단에 제시하고, 오프-타겟 부위는 온-타겟에 대한 미스매치를 강조하여 아래에 열거하였다. 오프-타겟 부위에서 야생형 SpCas9에 비해 D1135E에 의한 활성의 배수 감소가 온-타겟 부위에서의 활성의 변화에 비해 더 큰 것은 녹색으로 강조하였고, 각각의 앰플리콘에 대한 대조군 indel 수준을 기록하였다. f, D1135E를 이용한 온- 및 오프-타겟 부위에서의 활성의 배수 감소를 야생형 SpCas9에 의해 관찰된 indel 빈도와 비교하여 플롯팅한, 표적화된 심층-시퀀싱 데이터의 요약. g, D1135E를 이용한 특이성에서의 정규화된 배수-변화를 야생형 SpCas9를 이용한 오프-타겟 부위에서의 판독 카운트와 비교하여 플롯팅한, 오프-타겟 부위에서 GUIDE-seq에 의해 검출된 야생형과 D1135E 사이의 특이성 변화 (도 18c 또한 참고). D1135E에 대한 판독 카운트가 없는 부위에서의 특이성의 추정된 배수-증가는 플롯팅하지 않았다 (도 18c 참고).
도 4 | 박테리아 및 인간 세포에서 St1Cas9 및 SaCas9 이종상동유전자의 특성분석. a, 2가지 무작위화된 PAM 라이브러리를 이용한 St1Cas9에 대한 PPDV 산점도. PAM을 그들의 제3/제4/제5/제6 위치에 의해 분류하여 플롯팅하였다. 20 및 21 뉴클레오티드의 sgRNA 상보성 길이를 이용하여 양쪽 라이브러리에 대해 St1Cas9를 프로그래밍하였다 (각각 좌측 및 우측 패널). 적색 점선은 통계적으로 유의하게 고갈된 PAM을 나타내고 (도 13c 참고), 회색 점선은 5배 고갈을 나타내고 (0.2의 PPDV), α, 생물정보 접근법에 의해 이전에 확인된 PAM27; β, 엄격한 실험 조건 하에 이전에 확인된 PAM20; *, 이 연구에서 발견된 신규한 PAM; γ, 온건한 실험 조건 하에 이전에 확인된 PAM20. b, 2가지 무작위화된 PAM 라이브러리를 이용한 SaCas9에 대한 PPDV 산점도. PAM을 그들의 제3/제4/제5/제6 위치에 의해 분류하여 플롯팅하였다. 21 및 23 뉴클레오티드의 sgRNA 상보성 길이를 이용하여 양쪽 라이브러리에 대해 SaCas9를 프로그래밍하였다 (각각 좌측 및 우측 패널). SaCas9에 대해 확인된 PAM을 제시하였고, PAM 1-3은 이들 실험에서 사용된 스페이서 및 스페이서 길이의 모든 조합에서 일관되게 고갈되었다. c, x-축에 나타낸 상이한 표적 부위 및 PAM을 보유하는 선택 플라스미드로 시도할 때 박테리아 양성 선택에서 St1Cas9 및 SaCas9의 생존 백분율. St1Cas9 및 SaCas9에 대한 패널 (a) 및 (b)로부터의 고도로 고갈된 PAM을 양성 선택 플라스미드에서 표적 부위에 대해 사용하였다. d, e, 각각 NNAGAA (서열식별번호:3) 또는 NNGGGT (서열식별번호:4) / NNGAGT (서열식별번호:5) PAM을 함유하는 EGFP 부위에 대한 St1Cas9 (패널 d) 또는 SaCas9 (패널 e)의 EGFP 파괴 활성. 동일한 부위에 대해 상이한 길이를 갖는 매칭된 sgRNA를 나타내었고, 파괴 빈도를 유세포 분석법에 의해 정량화하고, 음성 대조군을 이용하여 수득된 EGFP 파괴의 평균 빈도를 적색 점선으로 나타내고, 오차 막대는 s.e.m., n = 3을 나타낸다. f, g, 각각 NNAGAA (서열식별번호:3) 또는 NNGGGT (서열식별번호:4) / NNGAGT (서열식별번호:5) / NNGAAT (서열식별번호:6) PAM을 함유하는 4가지 내인성 인간 유전자에 있는 부위에서 T7E1 검정에 의해 정량화된 St1Cas9 (패널 f) 및 SaCas9 (패널 g)의 돌연변이 빈도. 오차 막대는 s.e.m., n = 3을 나타내고, n.d.는 T7E1에 의해 검출불가능함이다.
도 5A- J. 서열 및 맵 - 이 연구에서 사용된 플라스미드
Figure pct00001

Figure pct00002

도 6 | SaCas9의 PAM-상호작용 잔기를 예상하기 위해 Cas9 이종상동유전자 의 정 렬. SpCas9, SaCas9, 및 11가지 다른 Cas9 이종상동유전자의 PAM-상호작용 도메인을 정렬하여, SpCas9에 대해 공지된 것을 기준으로 하여 SaCas9에서의 PAM 함유 잔기를 식별하였다. 각각 상단, 상단, 에스. 피오게네스, 서열식별번호:1의 아미노산 1229-1368, 이어서 서열식별번호:29-40.
도 7 | 박테리아 스크린에서 상이한 PAM에 대한 활성에 대해 평가된 SaCas9에서의 치환. 도 6의 정렬을 기준으로, 표준적인 NNGAGT (서열식별번호:5) 및 비-표준적인 NNAAGT (서열식별번호:41) 및 NNAGGT (서열식별번호:42) PAM에 대한 활성에 대한 효과를 스크리닝하기 위해 단일 아미노산 치환을 박테리아 양성 선택에서 시험하였다. 선택적 배지 상의 박테리아 콜로니는, SaCas9 변이체가 지정된 PAM을 함유하는 부위에 대해 활성을 가짐을 시사한다.
도 8A-B | SaCas9 변이체가 NNARRT ( 서열식별번호:43 ) PAM을 표적화할 수 있게 하는 아미노산 치환의 요약. NNARRT (서열식별번호:43) PAM을 함유하는 부위에 대해 박테리아에서 생존을 가능하게 하는 52가지 선택된 돌연변이체 SaCas9 클론의 PAM-상호작용 도메인의 아미노산 서열; 제시된 서열은 표 6에 제시된 서열식별번호:53-104의 부분 서열이다.
도 9 | 야생형 및 조작된 SaCas9 변이체의 인간 세포 활성. 인간 세포 EGFP 리포터 검정에서 야생형, KKQ 및 KKH SaCas9의 활성을 NNRRRT (서열식별번호:45) PAM을 함유하는 부위에 대하여 평가하였다.
도 10. 박테리아에서 비-표준적인 PAM에 대한 SaCas9 활성, 및 R1015에서의 지정된 돌연변이가 동일한 비-표준적인 PAM에 대한 활성에 영향을 미치는 방법.
도 11. 조작된 변이체는 형태 NNNRRT의 PAM을 인식할 수 있다.
도 12A-B | SpCas9의 변경된 PAM 특이성 변이체를 조작하기 위해 사용된 박테리아-기재 양성 선택. a, 도 1b로부터의 양성 선택의 확장된 개략도 (좌측 패널), 및 SpCas9가 양성 선택에서 예상한 대로 거동함을 입증 (우측 패널). 스페이서 1, 서열식별번호:105; 스페이서 2, 서열식별번호:106. b, 변경된 PAM 인식 특이성을 갖는 SpCas9 변이체를 선택하도록 양성 선택을 조정하는 방법의 개략도. 무작위화된 PAM-상호작용 (PI) 도메인 (잔기 1097-1368)을 갖는 SpCas9 클론의 라이브러리를 변경된 PAM을 보유한 선택 플라스미드에 의해 시도하였다. 양성 선택 플라스미드를 분할함으로써 선택을 생존하는 SpCas9 변이체를 시퀀싱하여, 변경된 PAM 특이성을 가능하게 하는 돌연변이를 결정하였다.
도 13A-D | Cas9 뉴클레아제의 전반적인 PAM 특이성을 프로파일링하기 위한 박테리아 세포-기재 부위-고갈 검정. a, 도 1d로부터의 음성 선택을 예시하는 확장된 개략도 (좌측 패널), 및 야생형 SpCas9가 기능적 (NGG) 및 비-기능적 (NGA) PAM을 갖는 부위의 스크린에서 예상되는 바와 같이 거동함을 입증 (우측 패널). b, PAM 대신에 6가지 무작위화된 염기쌍을 함유하는 음성 선택 플라스미드 라이브러리를 구성함으로써 기능적 PAM에 대해 스크리닝하기 위해 부위-고갈 검정으로서 음성 선택을 이용하는 방법의 개략도. 관심 Cas9/sgRNA에 의해 분할된 PAM을 함유하는 선택 플라스미드는 고갈된 반면에, 분할되지 않은 (또는 불량하게 분할된) PAM은 유지되었다. 선택후 PAM의 빈도를 출발 라이브러리에서 그의 선택전 빈도와 비교하여, 선택후 PAM 고갈 값 (PPDV)을 계산하였다. 스페이서 1, 서열식별번호:105; 스페이서 2, 서열식별번호:106. c, d, 2가지 무작위화된 PAM 라이브러리에 대해 촉매 불활성 SpCas9 (dCas9) (그의 제2/제3/제4 위치에 의해 분류하여 플롯팅함)에 대한 PAM의 PPDV를 플롯팅함으로써, 통계적으로 유의한 PPDV에 대한 컷오프를 수립하였다 (c). 2가지 라이브러리에 대해 평균 PPDV로부터의 3.36 표준 편차의 역가를 계산하였고 ((d)에서 적색 선), 0.85 미만의 임의의 PPDV 편차가 dCas9 처리와 비교하여 통계적으로 유의함을 수립하였다 ((c)에서 적색 점선). (c)에서 회색 점선은 검정에서 5배 고갈을 나타낸다 (0.2의 PPDV).
도 14 | 부위-고갈 검정과 EGFP 파괴 활성의 일치. 데이터 점은 상응하는 PAM에 대해 라이브러리 1 및 2에서 관찰된 평균 PPDV (도 1f)에 대해 플롯팅된, VQR 및 EQR SpCas9 변이체 (도 1g)에서 2개의 NGAN 및 NGNG PAM 부위의 평균 EGFP 파괴를 나타낸다. 적색 점선은 통계적으로 유의하게 고갈된 PAM을 나타내고 (0.85의 PPDV, 도 13c 참고), 회색 점선은 5배 고갈을 나타낸다 (0.2의 PPDV). 평균 값은 95% 신뢰 구간으로 플롯팅되었다.
도 15 | NGAG PAM을 함유하는 내인성 제브라피쉬 부위에서 VQR SpCas9 변이체에 의해 유도된 삽입 또는 결실 돌연변이. 각각의 표적 좌위의 경우, 야생형 서열은 황색으로 강조한 프로토스페이서와 함께 상단에 제시하였고 (상보성 가닥 상에 존재하는 경우 녹색으로 강조함), PAM은 적색 밑줄친 텍스트로 표시하였다. 결실은 회색으로 강조한 적색 점선으로 제시하였고, 삽입은 청색으로 강조한 소문자로 도시하였다. 각각의 indel 돌연변이에 의해 초래된 길이의 순 변화는 우측 (+, 삽입; -, 결실)에 제시하였다. 일부 변경은 서열의 삽입 및 결실 둘 다를 가졌고, 이들 경우에는 변경을 괄호안에 나열하였다. 각각의 돌연변이체 대립유전자가 회수된 배수 (1배 초과인 경우)를 괄호안에 제시하였다.
도 16A-B | SpCas9의 야생형 및 진화된 변이체에 의해 표적화된 내인성 유전자. a, 야생형, VQR 및 VRER SpCas9에 의해 표적화된 서열을 각각 청색, 적색 및 녹색으로 제시하였다. T7E1을 위해 이들 좌위를 증폭시키는데 사용된 sgRNA 및 프라이머의 서열은 하기 표 1 및 2에 제공되어 있다. b, 4가지 상이한 내인성 인간 유전자에서 NGG PAM을 보유하는 8개의 표적 부위에서 야생형 SpCas9에 대해 T7E1에 의해 검출된 평균 돌연변이 유발 빈도 (상단 패널의 주석에 상응함). 오차 막대는 s.e.m., n = 3을 나타낸다.
도 17A-B | GUIDE-seq 를 이용하여 결정된 VQR 및 VRER SpCas9 변이체의 특이성 프로파일. 의도된 온-타겟 부위는 흑색 사각형으로 표시하고, 오프-타겟 부위 내에서의 미스매칭된 위치는 강조하였다. a, VQR 변이체의 특이성은 인간 세포에서 NGA PAM을 함유하는 내인성 부위: EMX1 부위 4 (서열식별번호:142), FANCF 부위 1 (서열식별번호:143), FANCF 부위 3 (서열식별번호:144), FANCF 부위 4 (서열식별번호:145), RUNX1 부위 1 (서열식별번호:146), RUNX1 부위 3 (서열식별번호:147), VEGFA 부위 1 (서열식별번호:148), 및 ZSCAN2 (서열식별번호:149)를 표적화함으로써 평가하였다. b, VRER 변이체의 특이성은 인간 세포에서 NGCG PAM을 함유하는 내인성 부위: FANCF 부위 3 (서열식별번호:150), FANCF 부위 4 (서열식별번호:151), RUNX1 부위 1 (서열식별번호:152), VEGFA 부위 1 (서열식별번호:153), 및 VEGFA 부위 2 (서열식별번호:154)를 표적화함으로써 평가하였다.
도 18A-C | GUIDE-seq 에 의해 검출된 오프 - 타겟 부위에서 D1135E와 야생형 SpCas9 사이의 활성 차이. a, 제한 단편 길이 다형 분석에 의해 추정된, 온-타겟 부위에서 올리고 태그 통합의 평균 빈도. 오차 막대는 s.e.m., n = 4를 나타낸다. b, T7E1에 의해 검출된, 온-타겟 부위에서 평균 돌연변이 유발 빈도. 오차 막대는 s.e.m., n = 4를 나타낸다. c, 3가지 내인성 인간 세포 부위 (EMX1 부위 3 (서열식별번호:155); ZNF629 부위 (서열식별번호:156), VEGFA 부위 3 (서열식별번호:157))에서 야생형 SpCas9와 D1135E 사이의 GUIDE-seq 판독-카운트 차이. 온-타겟 부위는 상단에 제시하였고, 오프-타겟 부위는 미스매치를 강조하여 아래에 열거하였다. 표에서, 온-타겟 활성에 대한 오프-타겟 활성의 비를 야생형과 D1135E 사이에서 비교하여, 특이성에서의 정규화된 배수-변화를 계산하였다 (특이성 증가는 녹색으로 강조함). 검출가능한 GUIDE-seq 판독이 없는 부위의 경우에는, 1의 값을 지정하여 특이성에서의 추정된 변화를 계산하였다 (오렌지색으로 표시함). 도 3e에서 심층-시퀀싱에 의해 분석된 오프-타겟 부위를 EMX1 부위 3 및 VEGFA 부위 3 오프-타겟 부위의 좌측에 넘버링하였다.
도 19A-F | St1Cas9 및 SaCas9에 대한 추가의 PAM, 및 인간 세포에서 스페이 서 길이를 기재로 하는 활성. a, 스페이서 1 (상단 패널) 또는 스페이서 2 (하단 패널)에 대해 무작위화된 PAM 라이브러리를 이용하여 수득된 20 및 21 뉴클레오티드의 sgRNA 상보성 길이를 비교하는 St1Cas9에 대한 PPDV 산점도. PAM을 그들의 제3/제4/제5/제6 위치에 의해 분류하여 플롯팅하였다. 적색 점선은 통계적으로 유의하게 고갈된 PAM을 나타내고 (도 13c 참고), 회색 점선은 5배 고갈을 나타낸다 (0.2의 PPDV). b, 각각 4가지 시험된 조건 하에 St1Cas9에 대해 0.2 미만의 PPDV를 갖는 PAM의 표. 좌측에 제시한 PAM 번호는 도 4a에서와 동일하다. c, 스페이서 1 (상단 패널) 또는 스페이서 2 (하단 패널)에 대해 무작위화된 PAM 라이브러리를 이용하여 수득된 21 및 23 뉴클레오티드의 sgRNA 상보성 길이를 비교하는 SaCas9에 대한 PPDV 산점도. PAM을 그들의 제3/제4/제5/제6 위치에 의해 분류하여 플롯팅하였다. 적색 및 회색 점선은 (a)에서와 동일하다. d, 각각 4가지 시험된 조건 하에 SaCas9에 대해 0.2 미만의 PPDV를 갖는 PAM의 표. PAM 번호는 도 4b에서와 동일하다. e, f, EGFP 파괴를 통해 다양한 스페이서 길이에 걸쳐 St1Cas9 및 SaCas9의 인간 세포 활성 (패널 e, 도 4d, 4e로부터의 데이터) 및 T7E1에 의해 검출된 내인성 유전자 돌연변이 유발 (패널 f, 도 4f, 4g로부터의 데이터). 모든 복제물의 활성을 제시하였고 (n = 3 또는 4); 막대는 평균 및 95% 신뢰 구간을 예시하고; 스페이서 길이당 부위의 개수를 표시하였다.
도 20A-B | SpCas9에 의한 PAM 인식에서 D1135, G1218 및 T1337의 구조적 및 기능적 역할. a, PAM 인식과 관련있는 6가지 잔기의 구조적 표현. 좌측 패널은 PAM15의 제3 염기 위치와 물-매개된 작은 홈 접촉을 만드는 잔기인 S1136과 D1135의 근접성을 예시한다. 우측 패널은 PAM15의 제3 염기 위치와 직접적인 염기-특이적 큰 홈 접촉을 만드는 잔기인 R1335와 G1218, E1219 및 T1337의 근접성을 예시한다. 옹스트롬 거리는 황색 점선으로 표시하고, PAM의 비-표적 가닥 구아닌 염기 dG2 및 dG3은 청색으로 제시하고, 다른 DNA 염기는 오렌지색으로 제시하고, 물 분자는 적색으로 제시하고, 영상은 PDB:4UN3으로부터 PyMOL을 사용하여 생성하였다. b, PAM 인식과 관련있는 SpCas9의 6가지 잔기의 돌연변이 분석. 각각의 위치에서 3가지 돌연변이 유형 중 하나를 함유하는 클론을, NGG PAM을 보유하는 부위로 표적화된 2개의 sgRNA를 이용하여 EGFP 파괴에 대해 시험하였다. 각각의 위치에 대해, 본 발명자들은 알라닌 치환 및 2가지 비-보존적 돌연변이를 생성하였다. S1136 및 R1335는 PAM15의 제3 구아닌과의 접촉을 매개하는 것으로 이전에 보고되었고, D1135, G1218, E1219 및 T1337은 본 연구에서 보고한다. EGFP 파괴 활성은 유세포 분석법에 의해 정량화하고, 백그라운드 대조군은 적색 점선으로 나타내고, 오차 막대는 s.e.m., n = 3을 나타낸다.
도 21A-F 변경된 PAM 특이성을 갖는 SaCas9 변이체의 선택 및 조립. (a) SpCas9 및 SaCas9를 강조한 Cas9 이종상동유전자의 계통수. (b) 박테리아 양성 선택 검정에서 평가된, 단일 아미노산 치환을 갖는 SaCas9 변이체의 활성 (도 31b 또한 참고). 오차 막대는 s.e.m., n = 3을 나타내고, NS = 생존하지 못함이다. (c) 야생형 및 R1015H SaCas9의 인간 세포 활성. EGFP 파괴 활성은 유세포 분석법에 의해 정량화하고, 오차 막대는 s.e.m, n = 3을 나타내고, 백그라운드 EGFP 손실의 평균 수준은 적색 점선으로 나타내었다 (이 패널 및 패널 e의 경우). (d) 변경된 PAM 특이성을 갖는 SaCas9 변이체에 대해 선택할 때, 각각의 아미노산 위치에서 관찰된 치환의 총 개수. R1015에서의 스타터 돌연변이는 카운트하지 않았다. (e) 변경된 PAM 특이성에 대해 선택할 때 관찰된 돌연변이를 함유하는 변이체의 인간 세포 EGFP 파괴 활성. (f) KKH 변이체에 대한 야생형 SaCas9의 평균 선택후 PAM 고갈 값 (PPDV) 산점도 (n = 2, 도 34c 또한 참고). PAM 대신에 상이한 프로토스페이서 및 8개의 무작위화된 염기쌍을 갖는 2가지 라이브러리를 사용하여, PAM이 각각의 Cas9에 의해 표적화 가능한지를 결정하였다. 통계적으로 유의한 고갈은 적색 점선으로 표시하고 (dCas9 대조군과 비교, 도 34a 및 34b 참고), 5배 고갈은 회색 점선으로 표시하였다.
도 22A-F. 인간 세포에서 내인성 부위로 표적화된 SaCas9 KKH 변이체의 활성. (a) T7E1 검정에 의해 결정된, KKH SaCas9에 의해 유도된 NNNRRT PAM을 함유하는 55개의 상이한 부위에서 돌연변이 유발 빈도. 오차 막대는 s.e.m., n = 3을 나타내고, ND는 T7E1 검정에 의해 검출불가능함을 나타낸다. (b) PAM의 제3 위치에 대한 KKH 변이체 선호도. 패널 a에서의 데이터로부터의 평균 활성을 이 패널 및 패널 b 및 c에 제시하였다. (c) PAM의 제4 및 제5 위치에 대한 KKH 변이체 선호도. (d) KKH SaCas9 변이체의 스페이서 길이 선호도. (e) NNNRRT PAM을 함유하는 다양한 부위로 표적화된 야생형 및 KKH SaCas9의 인간 세포 EGFP 파괴 활성의 비교. EGFP 파괴는 유세포 분석법에 의해 정량화하고, 오차 막대는 s.e.m, n = 3을 나타내고, 백그라운드 EGFP 손실의 평균 수준은 적색 점선으로 나타내었다. (f) 패널 a로부터 가능한 16가지 NNNRRT 부위 각각에 대해 한 부위에서의 야생형 SaCas9의 돌연변이 유발 빈도 (가장 높은 KKH 활성을 갖는 부위를 선택함). 오차 막대는 s.e.m., n = 3을 나타내고, ND는 T7E1 검정에 의해 검출불가능함을 나타낸다.
도 23A-E 야생형 및 KKH SaCas9의 게놈에 걸친 특이성 프로파일. (a) 및 (b) EMX 부위 1 (서열식별번호:158) 및 VEGF 부위 8 (서열식별번호:159)에서 오프-타겟의 총 개수 (패널 a) 및 각각의 오프-타겟 부위에서 관찰된 미스매치 (패널 b)로 나타낸, NNGRRT (서열식별번호:46) PAM을 함유하는 부위로 표적화된 야생형 및 KKH SaCas9의 직접적인 비교. 패널 b 및 e의 경우, 각각의 부위에서의 GUIDE-seq 판독 카운트를 표시하고, 온-타겟 서열은 흑색 박스로 표시하고, 오프-타겟 부위 내의 미스매칭된 위치는 강조하고, 서열은 세포-유형 특이적 SNP에 대해 보정하고,잠재적인 sgRNA 또는 DNA 벌지(bulge) 뉴클레오티드를 갖는 부위는 각각 작은 적색-테두리 염기 또는 점선으로 나타내었다. (c) VEGFA 부위 8에서 야생형 및 KKH SaCas9에 의한 오프-타겟 부위 분할의 차이를 강조한 벤 다이어그램. (d) 및 (e) 오프-타겟의 총 개수 (패널 d) 및 각각의 오프-타겟 부위에서 관찰된 미스매치 (패널 e)로 나타낸, NNHRRT (서열식별번호:44) PAM을 갖는 부위인, EMX 부위 1 (서열식별번호:160), EMX 부위 4 (서열식별번호:161), EMX 부위 10 (서열식별번호:162), FANCF 부위 9 (서열식별번호:163), 및 FANCF 부위 16 (서열식별번호:164)로 표적화된 KKH 변이체의 특이성 프로파일.
도 24: 박테리아 2-플라스미드 스크린에서 VQR -유도체 클론의 활성. NGAN PAM을 함유하는 박테리아의 부위에 대한 24가지 상이한 VQR 유도체 변이체의 시험. 비-선택적 플레이트와 비교한 선택적 플레이트 상에서의 생존은 지정된 PAM에 대한 활성의 지표이다.
도 25: SpCas9-VQR 유도체의 인간 세포 EGFP 파괴 활성. SpCas9 변이체의 EGFP 파괴 활성은 지정된 PAM을 함유하는 부위에 대한 활성의 척도이다.
도 26: SpCas9-VQR 및 -VRQR 변이체의 인간 세포 EGFP 파괴 활성. SpCas9 변이체의 EGFP 파괴 활성은 지정된 PAM을 함유하는 부위에 대한 활성의 척도이다.
도 27: 박테리아 2-플라스미드 스크린에서 SpCas9-VRQR 유도체 변이체의 활성. VQR 및 VRQR 변이체와 비교한, NGAN PAM을 함유하는 박테리아의 부위에 대한 12가지 상이한 VQR 유도체 변이체의 시험. 비-선택적 플레이트와 비교한 선택적 플레이트 상에서의 생존은 지정된 PAM에 대한 활성의 지표이다.
도 28: SpCas9-VRQR 변이체의 인간 세포 EGFP 파괴 활성. SpCas9 변이체의 EGFP 파괴 활성은 지정된 PAM을 함유하는 부위에 대한 활성의 척도이다.
도 29 Cas9 이종상동유전자 (도 21a로부터)의 단백질 도메인 정렬. SpCas9의 도메인 구조는 상단에 제시하고 (PDB:4UN3을 기준으로; Anders et al., 2014), SpCas9의 PAM 접촉 잔기는 강조하고, 변경된 PAM 특이성 변이체를 선택하도록 돌연변이된 SaCas9 영역을 제시하였다.
도 30 PAM-상호작용 잔기의 식별을 위한 Cas9 이종상동유전자의 일차 서열 정렬; 각각 서열식별번호:165-176. PAM 접촉을 위해 중요하는 것으로 이전에 확인된 SpCas9 잔기 (Anders et al., 2014; 실시예 1-2)는 청색으로 강조하고, SaCas9 PAM 특이성을 조정할 수 있는 잔기 (이 연구에서 확인됨)는 오렌지색으로 강조하고, R1015에 인접한 양으로 하전된 잔기는 황색으로 강조하였다. 구조적으로 예상된 SpCas9의 PAM-상호작용 도메인은 청색 점선으로 강조하고 (PDB:4UN3을 기준으로; Anders et al., 2014), PCR 돌연변이 유발을 위한 경계로서 사용된 SaCas9 PAM-상호작용 도메인의 보존적 추정은 오렌지색 점선으로 나타내었다.
도 31A-B 박테리아 양성 선택 검정의 개략도. (a) 선택 플라스미드는 대안적인 PAM 서열을 인식할 수 있는 Cas9 변이체를 스크리닝하도록 변형시킬 수 있다. (b) 양성 선택에서 기능적 또는 비-기능적 Cas9/sgRNA 쌍을 스크리닝할 때 양성 선택 플라스미드 (좌측 패널) 및 예상된 결과 (우측 패널)의 개략도.
도 32 KNH 및 KKH 변이체로 K929R 돌연변이의 추가. EGFP 파괴 활성은 유세포 분석법에 의해 정량화하고, 오차 막대는 s.e.m, n = 3을 나타내고, 백그라운드 EGFP 손실의 평균 수준은 적색 점선으로 나타내었다.
도 33 박테리아 부위-고갈 검정의 개략도. 야생형 또는 KKH SaCas9에 의한 분할에 불응성인 PAM 대신에 8개의 무작위화된 뉴클레오티드를 갖는 부위-고갈 플라스미드를 시퀀싱하였다. 라이브러리 1 스페이서 서열, 서열식별번호:105; 라이브러리 2 스페이서 서열, 서열식별번호:106. 표적화가능한 PAM은, 선택후 PAM 고갈 값 (PPDV)으로서 계산되는, 투입 라이브러리와 비교한 그들의 고갈에 의해 추론하였다.
도 34A-E 야생형 및 KKH SaCas9에 대한 부위-고갈 검정 결과. (a) 양쪽 라이브러리에 대한 dCas9 대조군 실험의 PPDV 값. 적색 점선은 통계적 유의성을 나타내고 (PPDV = 0.794, 패널 b 참고), 회색 점선은 5배 고갈을 나타내고, PAM의 제3/제4/제5/제6 위치를 포함하는 윈도우에 대한 PPDV를 플롯팅하였다 (이 패널 및 패널 c의 경우). (b) 통계적으로 유의한 선택후 PAM 고갈 값 (PPDV)을 패널 a에서의 dCas9 대조군 실험으로부터 결정하였다. 통계적 유의성은 역가를 표준 편차의 3.36배로 설정함으로써 결정하였다. (c) PAM 대신에 8개의 무작위화된 뉴클레오티드를 함유하는 2가지 라이브러리 각각에 대해 야생형 및 KKH SaCas9에 대한 PPDV의 비교. (d) 및 (e) PAM, 및 각각 야생형 및 KKH SaCas9에 대해 5배 초과로 고갈된 모든 PAM에 대해 상응하는 PPDV 값. 서열 모티프는 2가지 카테고리: 1) 10배 초과 고갈 또는 2) 5배 내지 10배 고갈에서 PAM에 대해 제시하였다.
도 35A-D KKH SaCas9에 의해 표적화된 내인성 부위의 추가의 특성. (a) NNNRRT PAM의 가능한 16가지 NRR 모티프를 기준으로 비닝된(binned), 55개의 내인성 부위 sgRNA 각각에 대한 활성. 도 2a로부터의 평균 활성을 이 패널 및 패널 b 및 c에 제시하였다. (b) 및 (c) 내인성 유전자 파괴 활성과 스페이서 및 PAM 각각의 GC 함량 사이의 관계. (d) 활성을 기준으로 비닝된, 표적 부위의 스페이서 및 PAM에 대한 서열 로고. 부위는 평균 돌연변이 빈도 (도 2a로부터)를 기준으로 낮은 (0-10%, 17개 부위), 중간 (10-30%, 17개 부위) 또는 높은 (>30%, 21개 부위) 활성으로 분류하였다.
도 36A-B GUIDE-seq 실험에 대한 온-타겟 태그 통합 및 돌연변이 유발 빈도. (a) 평균 GUIDE-seq 태그 통합 빈도를 결정하기 위한 제한 단편 길이 다형 (RFLP) 분석. 오차 막대는 s.e.m., n = 3을 나타낸다 (이 패널 및 패널 b의 경우). (b) 평균 돌연변이 유발은 T7E1 검정에 의해 검출하였다.
도 37A-B 말단절단된 반복부:항-반복부 sgRNA는 전장 sgRNA를 능가하고, 이는 이전의 결과와 유사하다 (Ran et al., 2015). (a) NNGRRT (서열식별번호:46) PAM을 함유하는 4가지 부위에 대한 야생형 SaCas9의 인간 세포 EGFP 파괴 활성. EGFP 파괴 활성은 유세포 분석법에 의해 정량화하고, 오차 막대는 s.e.m, n = 3을 나타내고, 백그라운드 EGFP 손실의 평균 수준은 적색 점선으로 나타내었다 (이 패널 및 패널 b의 경우). (b) NNNRRT PAM을 함유하는 8가지 부위에 대한 KKH SaCas9의 인간 세포 EGFP 파괴 활성.
CRISPR-Cas9 뉴클레아제가 게놈 편집을 위해 널리 사용되지만1 -4, Cas9를 분할할 수 있는 서열의 범위는 표적 부위에서 특이적 프로토스페이서 인접 모티프 (PAM)에 대한 요구에 의해 제한된다5 , 6. 예를 들어, 지금까지 가장 강력하고 널리 사용되는 Cas9인 SpCas9는 일차적으로 NGG PAM을 인식한다. 그 결과, 종종 다양한 게놈 편집 적용에 필요한 이중-가닥 절단부 (DSB)를 정확히 표적화하는 것이 어려울 수 있다. 또한, Cas9에 의한 불완전한 PAM 인식은 원치않는 오프-타겟 돌연변이의 생성을 초래할 수 있다7 , 8. 목적을 위해 변경된 또는 개선된 PAM 특이성을 갖는 Cas9 유도체를 진화시키는 능력이 이들 제한을 다룰 것이지만, 본 발명자들의 지식으로는 이러한 Cas9 변이체가 기재된 적이 없다.
연장된 PAM을 인식하는 직교형 Cas9의 표적화 범위를 개선시키는 잠재적인 전략은 그의 PAM 인식 특이성을 변경시키는 것이다. 본원에 기재된 바와 같이, SpCas9의 PAM 인식 특이성은 박테리아 세포-기재 선택 시스템을 이용하여 수행되는 구조-지시된 고안 및 직접적인 진화에 의해 변경될 수 있으며, 실시예 1 및 2를 참고한다. 또한, 본원에는 PAM 내의 특정 위치에 대해 완화된 또는 부분적으로 완화된 특이성을 갖도록 진화된 변이체가 기재되며, 실시예 3을 참고한다. 이들 변이체는 더 긴 PAM 서열에 대해 특이성을 갖는 Cas9 이종상동유전자의 유용성을 확장시킨다.
변경된 PAM 특이성을 갖는 조작된 Cas9 변이체
이 연구에서 조작된 SpCas9 변이체는 야생형 SpCas9에 의해 접근가능한 부위를 크게 증가시키고, 추가로 CRISPR-Cas9 플랫폼을 사용하는 기회를 개선시켜 효율적인 HDR을 실시하고, NHEJ-매개된 indel을 작은 유전자 요소로 표적화하고, 동일한 세포에서 두가지 상이한 대립유전자를 구별하기 위한 PAM의 요건을 개발한다. 변경된 PAM 특이성 SpCas9 변이체는, 현재 제브라피쉬 배아 및 인간 세포 둘 다에서 SpCas9에 의해 표적화될 수 없는 내인성 유전자 부위를 효율적으로 파괴할 수 있으며, 이는 이들이 다양한 상이한 세포 유형 및 유기체에서 작용할 것임을 시사한다. 중요하게는, GUIDE-seq 실험은, VQR 및 VRER SpCas9 변이체의 전반적인 프로파일이 야생형 SpCas9에서 관찰된 것과 유사하거나 그보다 양호함을 제시한다. 또한, 본 발명자들이 확인하여 특성분석한 개선된 특이성 D1135E 변이체는 널리 사용되는 야생형 SpCas9에 대한 우수한 대안을 제공한다. D1135E는 표준적인 NGG PAM을 갖는 부위에 대해 야생형 SpCas9와 유사한 활성을 갖지만, 미스매칭된 스페이서 서열 및 표준적인 또는 비-표준적인 PAM을 보유하는 오프-타겟 부위의 게놈에 걸친 분할을 감소시킨다.
본원에 기재된 모든 SpCas9 및 SaCas9 변이체는 예를 들어 간단한 부위-지정 돌연변이 유발에 의해 존재하는 널리 사용되는 벡터에 신속히 도입될 수 있고, 이들이 PAM-상호작용 도메인 내에 함유된 단지 얼마 안되는 돌연변이를 필요로 하기 때문에, 변이체는 또한 SpCas9 플랫폼 (예를 들어, 말단절단된 sgRNA (Tsai et al., Nat Biotechnol 33, 187-197 (2015); Fu et al., Nat Biotechnol 32, 279-284 (2014)), 니카제 돌연변이 (Mali et al., Nat Biotechnol 31, 833-838 (2013); Ran et al., Cell 154, 1380-1389 (2013)), 이량체 FokI-dCas9 융합 (Guilinger et al., Nat Biotechnol 32, 577-582 (2014); Tsai et al., Nat Biotechnol 32, 569-576 (2014))에 대해 이전에 기재된 다른 개선을 가지면서 작용해야 한다.
제3 PAM 염기 위치와 아마도 접촉하는 R1335에 대한 돌연변이 외에도, 이 연구에서 진화된 SpCas9 변이체는 D1135, G1218 및 T1337에서 아미노산 치환을 보유하고, 이들 모두는 SpCas9-PAM 구조에서 제3 PAM 위치와의 직접적인 또는 간접적인 접촉을 만드는 잔기 근처에 또는 인접하여 위치하지만 그 자체는 PAM 염기와의 접촉을 매개하지 않는다 (Anders et al., Nature 513, 569-573 (2014)) (도 20a). 이와 일치하게, 본 발명자들은 이들 위치에서의 다양한 돌연변이가 NGG PAM을 보유하는 부위의 SpCas9-매개된 분할에 영향을 미치는 것으로 여겨지지는 않음을 확인하였다 (도 20b). 이들 결과는 VQR 및 VRER SpCas9 변이체의 G1218 및 T1337에서의 아미노산 치환의 특성과 함께, 이들 두 위치에서의 변경이 기능-획득 돌연변이일 수 있음을 시사한다. 예를 들어, T1337R 돌연변이는 특히 VRER 변이체의 경우에는 PAM의 제4 위치와의 또는 그 근처와의 백본 또는 염기-특이적 접촉을 형성하는 것이 가능하다. D1135에서의 돌연변이의 메카니즘적 역할은 덜 명백하지만, 이들은 아마도 PAM의 제3 위치에서 작은 홈을 통해서 구아닌과의 물-매개된 접촉을 만드는 것과 관련이 있는 인접한 S1136 잔기의 활성에 영향을 미칠 수 있다 (Anders et al., Nature 513, 569-573 (2014)). D1135E 돌연변이는 이 네트워크를 파괴함으로써, 아마도 SpCas9/gRNA 복합체와 표적 부위의 전반적인 상호작용 에너지를 감소시킴으로써 특이성을 개선시킬 수 있으며, 본 발명자들이 이전에 제안한 메카니즘은 이들 원치않는 서열을 에너지적으로 덜 유리하게 분할함으로써 오프-타겟 효과를 감소시킬 수 있다 (Fu et al., Nat Biotechnol 32, 279-284 (2014)).
본 결과는 명백히 변경된 PAM 특이성을 갖는 Cas9 뉴클레아제 조작의 실현가능성을 수립한다. 이전에 기재된 바와 같이 추가의 Cas9 이종상동유전자의 특성분석 (Esvelt et al., Nat Methods 10, 1116-1121 (2013); Fonfara et al., Nucleic Acids Res 42, 2577-2590 (2014)) 또는 도메인-스와핑된 Cas9 키메라의 생성 (Nishimasu et al., Cell. 156(5):935-49 (2014))은 또한 상이한 PAM을 표적화하기 위한 잠재적인 방안을 제공한다. 본원에서 설명된 조작 전략은 또한 표적화가능한 PAM의 범위를 더욱 다양화시키기 위해 이러한 이종상동유전자 또는 합성 하이브리드 Cas9를 이용하여 수행할 수 있다. St1Cas9 및 SaCas9는 본 발명자들의 박테리아 선택 시스템에서 및 인간 세포에서 SpCas9에 비해 더 작은 그의 크기 및 그의 강력한 게놈 편집 활성에 대한 본 발명자들의 입증에 의해 추후의 조작 노력을 위한 특히 매력적인 프레임워크를 만든다.
본 발명자들의 결과는 야생형 SaCas9의 R1015가 제3 PAM 위치에 있는 G와 접촉한다는 것을 강력히 시사한다. 이론에 구애되기를 바라는 것은 아니지만, R1015H 치환이 제3 위치에서의 이러한 접촉을 제거하고 특이성을 완화시킬 수 있지만, R1015의 G 접촉으로의 손실은 또한 아마도 표적 부위 결합과 연관된 에너지를 감소시킬 수 있고, 이는 R1015H 돌연변이 단독이 인간 세포에서 NNNRRT 부위에 대한 강력한 활성에는 충분하지 않은 이유를 설명한다. E782K 및 N968K 치환 둘 다 양의 전하를 더하기 때문에, 이들이 DNA 포스페이트 백본과 비-특이적으로 상호작용하여 R1015의 구아닌 접촉으로의 손실에 대해 에너지적으로 보상하는 것이 가능하다.
본원에 기재된 유전학적 접근법은 구조적 정보를 필요로 하지 않고, 따라서 여러 다른 Cas9 이종상동유전자에 적용가능해야 한다. 확대된 PAM 특이성을 갖는 Cas9 뉴클레아제를 진화시키기 위한 유일한 요건은, 이들이 박테리아-기재 선택에서 기능하는 것이다. 이전의 연구에서 PAM 인식이 고도로 관련된 Cas9 이종상동유전자의 PAM-상호작용 도메인을 스와핑함으로써 변경될 수 있다고 입증하였지만 (Nishimasu et al., Cell (2014)), 이 전략이 더욱 다양한 이종상동유전자를 사용할 때 일반화가능하거나 효과적인지 여부가 결정되어야 한다. 대조적으로, 본 발명자들이 본원에 기재한 진화 전략은 천연 발생 Cas9 이종상동유전자 내에 코딩된 것들 외에도 PAM 인식 특이성을 조작하기 위해 사용될 수 있다. 이러한 전반적인 전략을 이용하여 천연에 존재하는 수많은 Cas9 이종상동유전자의 표적화 범위를 확대시키고 그의 유용성을 확장시킬 수 있다.
변경된 특이성을 갖는 SpCas9 변이체
따라서, 본원에는 spCas9 변이체가 제공된다. SpCas9 야생형 서열은 다음과 같다:
Figure pct00003
Figure pct00004
본원에 기재된 SpCas9 변이체는 하기 위치: D1135, G1218, R1335, T1337 중 하나 이상에서 (또는 그와 유사한 위치에서) 돌연변이를 포함할 수 있다. 일부 실시양태에서, SpCas9 변이체는 하기 돌연변이: D1135V; D1135E; G1218R; R1335E; R1335Q; 및 T1337R 중 하나 이상을 포함한다. 일부 실시양태에서, SpCas9 변이체는 서열식별번호:1의 아미노산 서열과 적어도 80%, 예를 들어 적어도 85%, 90% 또는 95% 동일하고, 예를 들어 서열식별번호:1의 잔기의 5%, 10%, 15% 또는 20%까지가 예를 들어 보존적 돌연변이에 의해 교체되어 차이가 있다. 바람직한 실시양태에서, 변이체는 모체의 바람직한 활성, 예를 들어 뉴클레아제 활성 (모체가 니카제 또는 데드 Cas9인 경우에는 제외) 및/또는 가이드 RNA 및 표적 DNA와 상호작용하는 능력을 보유한다.
두 핵산 서열의 퍼센트 동일성을 결정하기 위해, 서열을 최적 비교 목적을 위해 정렬시킨다 (예를 들어, 최적 정렬을 위해 제1 및 제2 아미노산 또는 핵산 서열 중 하나 또는 둘 다에 갭을 도입시킬 수 있고, 비교 목적을 위해 비-상동성 서열은 무시할 수 있음). 비교 목적을 위해 정렬된 기준 서열의 길이는 기준 서열 길이의 적어도 80%, 일부 실시양태에서는 적어도 90% 또는 100%이다. 이어서, 상응하는 아미노산 위치 또는 뉴클레오티드 위치에 있는 뉴클레오티드를 비교한다. 제1 서열에서의 위치가 제2 서열에서의 상응하는 위치와 동일한 뉴클레오티드에 의해 점유된 경우에는, 분자는 그 위치에서 동일하다 (본원에서 사용된 핵산 "동일성"은 핵산 "상동성"과 동등함). 두 서열 사이의 퍼센트 동일성은, 두 서열의 최적의 정렬을 위해 도입될 필요가 있는 갭의 개수 및 각 갭의 길이를 고려하여 서열에 의해 공유된 동일한 위치의 개수의 함수이다. 두 폴리펩티드 또는 핵산 서열 사이의 퍼센트 동일성은, 관련 기술분야의 기술 내에서 다양한 방식으로, 예를 들어 공개적으로 이용가능한 컴퓨터 소프트웨어, 예컨대 스미스 워터맨(Smith Waterman) 정렬 (Smith, T. F. and M. S. Waterman (1981) J Mol Biol 147:195-7); 진매처 플러스(GeneMatcher PlusTM, Schwarz and Dayhof (1979) Atlas of Protein Sequence and Structure, Dayhof, M.O., Ed, pp 353-358)에 도입된 "베스트핏(BestFit)" (Smith and Waterman, Advances in Applied Mathematics, 482-489 (1981)); BLAST 프로그램 (Basic Local Alignment Search Tool; Altschul, S. F., W. Gish, et al. (1990) J Mol Biol 215: 403-10), BLAST-2, BLAST-P, BLAST-N, BLAST-X, WU-BLAST-2, ALIGN, ALIGN-2, CLUSTAL, 또는 메그얼라인(Megalign) (DNASTAR) 소프트웨어를 이용하여 결정한다. 또한, 통상의 기술자는 정렬 측정을 위한 적절한 파라미터, 예컨대 비교하고자 하는 서열의 길이에 걸쳐 최대 정렬을 달성하기 위해 요구되는 임의의 알고리즘을 결정할 수 있다. 일반적으로, 단백질 또는 핵산의 경우, 비교의 길이는 전장을 포함하여 전장 이하의 임의의 길이일 수 있다 (예를 들어, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 또는 100%). 본 발명의 조성물 및 방법의 목적을 위해, 서열 전장의 적어도 80%를 BLAST 알고리즘 및 디폴트 파라미터를 이용하여 정렬시킨다.
본 발명의 목적을 위해, 서열의 비교 및 두 서열 사이의 퍼센트 동일성의 측정은 갭 패널티가 12이고 갭 익스텐드 패널티가 4이고 프레임쉬프트 갭 패널티가 5인 블로썸(Blossum) 62 스코어링 매트릭스를 이용하여 수행할 수 있다.
보존적 치환은 전형적으로 하기 군 내에서의 치환을 포함한다: 글리신, 알라닌; 발린, 이소류신, 류신; 아스파르트산, 글루탐산, 아스파라긴, 글루타민; 세린, 트레오닌; 리신, 아르기닌; 및 페닐알라닌, 티로신.
일부 실시양태에서, SpCas9 변이체는 하기 돌연변이 세트: D1135V/R1335Q/T1337R (VQR 변이체); D1135V/G1218R/R1335Q/T1337R (VRQR 변이체); D1135E/R1335Q/T1337R (EQR 변이체); 또는 D1135V/G1218R/R1335E/T1337R (VRER 변이체) 중 하나를 포함한다.
일부 실시양태에서, SpCas9 변이체는 또한 Cas9의 뉴클레아제 활성을 감소 또는 파괴하는 하기 돌연변이: D10, E762, D839, H983 또는 D986, 및 H840 또는 N863 중 하나, 예를 들어 D10A/D10N 및 H840A/H840N/H840Y를 포함하여, 단백질의 뉴클레아제 부분을 촉매 불활성으로 만들고, 이들 위치에서의 치환은 알라닌 (문헌 [Nishimasu al., Cell 156, 935-949 (2014)]에 기재된 바와 같이), 또는 다른 잔기, 예를 들어 글루타민, 아스파라긴, 티로신, 세린 또는 아스파르테이트일 수 있고, 예를 들어 E762Q, H983N, H983Y, D986N, N863D, N863S 또는 N863H일 수 있다 (WO 2014/152432 참고). 일부 실시양태에서, 변이체는 D10A 또는 H840A에서의 돌연변이 (이는 단일-가닥 니카제를 생성함), 또는 D10A 및 H840A에서의 돌연변이 (이는 뉴클레아제 활성을 방해하며, 이 돌연변이체는 데드 Cas9 또는 dCas9로 공지됨)를 포함한다.
또한, 본원에는 SaCas9 변이체가 제공된다. SaCas9 야생형 서열은 다음과 같다:
Figure pct00005
Figure pct00006
본원에 기재된 SaCas9 변이체는 하기 위치: E782, N968 및/또는 R1015 중 하나 이상에서 (또는 그위 유사한 위치에서) 돌연변이를 포함한다. 일부 실시양태에서, 변이체는 하기 돌연변이: R1015Q, R1015H, E782K, N968K, E735K, K929R, A1021T, K1044N 중 하나 이상을 포함한다. 일부 실시양태에서, SaCas9 변이체는 돌연변이 E782K, K929R, N968K 및 R1015X를 포함하고, 여기서 X는 R 이외의 임의의 아미노산이다. 일부 실시양태에서, SaCas9 변이체는 서열식별번호:2의 아미노산 서열과 적어도 80%, 예를 들어 적어도 85%, 90% 또는 95% 동일하고, 예를 들어 서열식별번호:2의 잔기의 5%, 10%, 15% 또는 20%까지가 예를 들어 보존적 돌연변이에 의해 교체되어 차이가 있다. 바람직한 실시양태에서, 변이체는 모체의 바람직한 활성, 예를 들어 뉴클레아제 활성 (모체가 니카제 또는 데드 Cas9인 경우에는 제외) 및/또는 가이드 RNA 및 표적 DNA와 상호작용하는 능력을 보유한다.
일부 실시양태에서, SaCas9 변이체는 또한 SaCas9의 뉴클레아제 활성을 감소 또는 파괴하는 하기 돌연변이: D10A, D556A, H557A, N580A 중 하나, 예를 들어 D10A/H557A 및/또는 D10A/D556A/H557A/N580A를 포함하여, 단백질의 뉴클레아제 부분을 촉매 불활성으로 만들고, 이들 위치에서의 치환은 알라닌 (문헌 [Nishimasu al., Cell 156, 935-949 (2014)]에 기재된 바와 같이), 또는 다른 잔기, 예를 들어 글루타민, 아스파라긴, 티로신, 세린 또는 아스파르테이트일 수 있다. 일부 실시양태에서, 변이체는 D10A, D556A, H557A 또는 N580A에서의 돌연변이 (이는 단일-가닥 니카제를 생성할 수 있음), 또는 D10A/H557A 및/또는 D10A/D556A/H557A/N580A에서의 돌연변이 (이는 SpCas9와의 유사성으로 인해 뉴클레아제 활성을 방해할 수 있으며, 이들은 데드 Cas9 또는 dCas9로도 지칭됨)를 포함한다.
또한, 본원에는 SpCas9 및/또는 SaCas9 변이체를 코딩하는 단리된 핵산, 변이체 단백질을 발현하기 위해 임의적으로 하나 이상의 조절 도메인에 작동가능하게 연결된 단리된 핵산을 포함하는 벡터, 및 핵산을 포함하고 임의적으로 변이체 단백질을 발현하는 숙주 세포, 예를 들어 포유동물 숙주 세포가 제공된다.
본원에 기재된 변이체를 이용하여 세포의 게놈을 변경시킬 수 있고, 상기 방법은 일반적으로 세포의 게놈의 선택된 부분에 상보적인 영역을 갖는 가이드 RNA와 함께 세포에서 변이체 단백질을 발현시키는 것을 포함한다. 세포의 게놈을 선택적으로 변경시키는 방법이 관련 기술분야에 공지되어 있으며, 예를 들어 US8,697,359; US2010/0076057; US2011/0189776; US2011/0223638; US2013/0130248; WO/2008/108989; WO/2010/054108; WO/2012/164565; WO/2013/098244; WO/2013/176772; US20150050699; US20150045546; US20150031134; US20150024500; US20140377868; US20140357530; US20140349400; US20140335620; US20140335063; US20140315985; US20140310830; US20140310828; US20140309487; US20140304853; US20140298547; US20140295556; US20140294773; US20140287938; US20140273234; US20140273232; US20140273231; US20140273230; US20140271987; US20140256046; US20140248702; US20140242702; US20140242700; US20140242699; US20140242664; US20140234972; US20140227787; US20140212869; US20140201857; US20140199767; US20140189896; US20140186958; US20140186919; US20140186843; US20140179770; US20140179006; US20140170753; Makarova et al., "Evolution and classification of the CRISPR-Cas systems" 9(6) Nature Reviews Microbiology 467-477 (1-23) (Jun. 2011); Wiedenheft et al., "RNA-guided genetic silencing systems in bacteria and archaea" 482 Nature 331-338 (Feb. 16, 2012); Gasiunas et al., "Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria" 109(39) Proceedings of the National Academy of Sciences USA E2579-E2586 (Sep. 4, 2012); Jinek et al., "A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity" 337 Science 816-821 (Aug. 17, 2012); Carroll, "A CRISPR Approach to Gene Targeting" 20(9) Molecular Therapy 1658-1660 (Sep. 2012); 2012년 5월 25일에 출원된 미국 출원 번호 61/652,086; Al-Attar et al., Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs): The Hallmark of an Ingenious Antiviral Defense Mechanism in Prokaryotes, Biol Chem. (2011) vol. 392, Issue 4, pp. 277-289; Hale et al., Essential Features and Rational Design of CRISPR RNAs That Function With the Cas RAMP Module Complex to Cleave RNAs, Molecular Cell, (2012) vol. 45, Issue 3, 292-302를 참고한다.
상기 참고문헌에 기재된 SpCas9 단백질 대신에 본원에 기재된 변이체 단백질을 하기 표 4에 따른 PAM 서열을 갖는 서열을 표적화하는 가이드 RNA와 함께 사용할 수 있다.
Figure pct00007
또한, 본원에 기재된 변이체는 야생형 Cas9 또는 관련 기술분야에 공지된 다른 Cas9 돌연변이 (예컨대, 상기 기재된 dCas9 또는 Cas9 니카제) 대신에 융합 단백질로, 예를 들어 WO 2014/124284에 기재된 이종 기능적 도메인과의 융합 단백질로 사용될 수 있다. 예를 들어, 바람직하게는 하나 이상의 뉴클레아제-감소 또는 사멸 돌연변이를 포함하는 변이체는 Cas9의 N 또는 C 말단 상에서 전사 활성화 도메인 또는 다른 이종 기능적 도메인, 예를 들어 전사 저해인자 (예를 들어, KRAB, ERD, SID 등, 예를 들어 ets2 저해인자 인자 (ERF) 저해인자 도메인 (ERD)의 아미노산 473-530, KOX1의 KRAB 도메인의 아미노산 1-97, 또는 Mad mSIN3 상호작용 도메인 (SID)의 아미노산 1-36; 문헌 [Beerli et al., PNAS USA 95:14628-14633 (1998)] 참고) 또는 사일런서, 예컨대 이질염색질 단백질 1 (HP1, swi6으로도 공지됨), 예를 들어 HP1α 또는 HP1β에 융합될 수 있고; 관련 기술분야에 공지된 바와 같이 고정된 RNA 결합 서열에 융합된 긴 비-코딩 RNA (lncRNA)를 동원할 수 있는 단백질 또는 펩티드, 예컨대 MS2 코트 단백질, 엔도리보뉴클레아제 Csy4, 또는 람다 N 단백질에 의해 결합된 것들; DNA의 메틸화 상태를 변경시키는 효소 (예를 들어, DNA 메틸트랜스퍼라제 (DNMT) 또는 TET 단백질); 또는 히스톤 서브유닛을 변경시키는 효소 (예를 들어, 히스톤 아세틸트랜스퍼라제 (HAT), 히스톤 데아세틸라제 (HDAC), 히스톤 메틸트랜스퍼라제 (예를 들어, 리신 또는 아르기닌 잔기의 메틸화를 위해) 또는 히스톤 데메틸라제 (예를 들어, 리신 또는 아르기닌 잔기의 탈메틸화를 위해)) 또한 이용될 수 있다. 이러한 도메인을 위한 수많은 서열이 관련 기술분야에 공지되어 있고, 예를 들어 DNA에서 메틸화된 시토신의 히드록실화를 촉매하는 도메인이 있다. 예시적인 단백질에는 DNA에서 5-메틸시토신 (5-mC)을 5-히드록시메틸시토신 (5-hmC)으로 전환시키는 효소인 텐-일레븐-트랜스로케이션(Ten-Eleven-Translocation, TET)1-3 패밀리가 포함된다.
인간 TET1-3에 대한 서열은 관련 기술분야에 공지되어 있고, 하기 표에 제시되어 있다:
Figure pct00008
* 변이체 (1)은 더 긴 전사체를 나타내고, 더 긴 이소형 (a)를 코딩한다. 변이체 (2)는 변이체 1에 비해 5' UTR 및 3' UTR에서 코딩 서열이 상이하다. 생성된 이소형 (b)는 더 짧고, 이소형 a와 구별되는 C-말단을 갖는다.
일부 실시양태에서, 촉매 도메인의 전장 서열 모두 또는 그의 일부, 예를 들어 시스테인-풍부 연장부, 및 7개의 고도로 보존된 엑손에 의해 코딩되는 2OGFeDO 도메인을 포함하는 촉매 모듈, 예를 들어 아미노산 1580-2052를 포함하는 Tet1 촉매 도메인, 아미노산 1290-1905을 포함하는 Tet2 및 아미노산 966-1678을 포함하는 Tet3이 포함될 수 있다. 예를 들어, 3가지 모든 Tet 단백질에서 주요 촉매 잔기를 예시하는 정렬을 위해 Iyer et al., Cell Cycle. 2009 Jun 1;8(11):1698-710. Epub 2009 Jun 27의 도 1을 참고하고, 전장 서열의 경우에는 그의 보충 자료를 참고하며 (예를 들어, seq 2c 참고); 일부 실시양태에서, 상기 서열은 Tet1의 아미노산 1418-2136 또는 Tet2/3에서의 상응하는 영역을 포함한다.
다른 촉매 모듈은 Iyer et al., 2009에서 확인된 단백질로부터의 것일 수 있다.
일부 실시양태에서, 이종 기능적 도메인은 생물학적 테더이며, MS2 코트 단백질, 엔도리보뉴클레아제 Csy4, 또는 람다 N 단백질의 모두 또는 일부 (예를 들어, 그로부터의 DNA 결합 도메인)를 포함한다. 이들 단백질을 사용하여, 특이적 스템-루프 구조를 함유하는 RNA 분자를 dCas9 gRNA 표적화 서열이 특이성을 갖는 부위로 동원하기 위해 사용될 수 있다. 예를 들어, MS2 코트 단백질, 엔도리보뉴클레아제 Csy4 또는 람다 N에 융합된 dCas9 변이체를 사용하여, Csy4, MS2 또는 람다 N 결합 서열에 연결된 긴 비-코딩 RNA (lncRNA), 예컨대 XIST 또는 HOTAIR을 동원할 수 있다 (예를 들어, Keryer-Bibens et al., Biol. Cell 100:125-138 (2008) 참고). 대안적으로, 예를 들어 상기 Keryer-Bibens et al.에서 기재된 바와 같이 Csy4, MS2 또는 람다 N 단백질 결합 서열은 또 다른 단백질에 연결될 수 있고, 상기 단백질은 본원에 기재된 방법 및 조성물을 이용하여 dCas9 변이체 결합 부위로 표적화될 수 있다. 일부 실시양태에서, Csy4는 촉매 불활성이다. 일부 실시양태에서, WO 2014/204578에 기재된 바와 같이 Cas9 변이체, 바람직하게는 dCas9 변이체는 FokI에 융합된다.
일부 실시양태에서, 융합 단백질은 dCas9 변이체와 이종 기능적 도메인 사이에 링커를 포함한다. 이들 융합 단백질에서 (또는 연결된 구조의 경우 융합 단백질들 사이에서) 사용될 수 있는 링커는 융합 단백질의 기능을 방해하지 않는 임의의 서열을 포함할 수 있다. 바람직한 실시양태에서, 링커는 예를 들어 2-20개 아미노산으로 짧고, 전형적으로 가요성이다 (즉, 높은 자유도를 갖는 아미노산, 예컨대 글리신, 알라닌 및 세린을 포함함). 일부 실시양태에서, 링커는 GGGS (서열식별번호:188) 또는 GGGGS (서열식별번호:189)로 이루어진 하나 이상의 유닛, 예를 들어 GGGS (서열식별번호:188) 또는 GGGGS (서열식별번호:189) 유닛의 2, 3, 4개 이상의 반복부를 포함한다. 다른 링커 서열 또한 사용될 수 있다.
발현 시스템
본원에 기재된 Cas9 변이체를 사용하기 위해, 그를 코딩하는 핵산으로부터 그를 발현시키는 것이 바람직할 수 있다. 이는 다양한 방식으로 수행될 수 있다. 예를 들어, Cas9 변이체를 코딩하는 핵산을 복제 및/또는 발현을 위한 원핵 또는 진핵 세포로 형질전환시키기 위해 중간체 벡터로 클로닝할 수 있다. Cas9 변이체를 생산하기 위해 Cas9 변이체를 코딩하는 핵산을 저장 또는 조작하기 위하여 중간체 벡터는 전형적으로 원핵생물 벡터, 예를 들어 플라스미드, 또는 셔틀 벡터, 또는 곤충 벡터이다. Cas9 변이체를 코딩하는 핵산을 또한 식물 세포, 동물 세포, 바람직하게는 포유동물 세포 또는 인간 세포, 진균 세포, 박테리아 세포, 또는 원생동물 세포에 투여하기 위해 발현 벡터로 클로닝할 수 있다.
발현을 달성하기 위해, 전형적으로 Cas9 변이체를 코딩하는 서열을 전사를 지시하는 프로모터를 함유하는 발현 벡터로 서브클로닝한다. 적합한 박테리아 및 진핵세포 프로모터는 관련 기술분야에 널리 공지되어 있고, 예를 들어 문헌 [Sambrook et al., Molecular Cloning, A Laboratory Manual (3d ed. 2001); Kriegler, Gene Transfer and Expression: A Laboratory Manual (1990); 및 Current Protocols in Molecular Biology (Ausubel et al., eds., 2010)]에 기재되어 있다. 조작된 단백질을 발현시키기 위한 박테리아 발현 시스템은 예를 들어 이. 콜라이(E. coli), 바실루스(Bacillus) 종, 및 살모넬라(Salmonella)에서 얻을 수 있다 (Palva et al., 1983, Gene 22:229-235). 이러한 발현 시스템을 위한 키트는 상업적으로 입수가능하다. 포유동물 세포, 효모, 및 곤충 세포를 위한 진핵세포 발현 시스템은 관련 기술분야에 널리 공지되어 있고, 또한 상업적으로 입수가능하다.
핵산 발현을 지시하는데 사용되는 프로모터는 특정한 적용에 따라 좌우된다. 예를 들어, 전형적으로 강력한 구성 프로모터는 융합 단백질의 발현 및 증식을 위해 사용된다. 대조적으로, Cas9 변이체를 유전자 조절을 위해 생체내로 투여하는 경우에는, Cas9 변이체의 특정한 용도에 따라 구성 또는 유도 프로모터가 사용될 수 있다. 또한, Cas9 변이체의 투여에 바람직한 프로모터는 약한 프로모터, 예컨대 HSV TK 또는 유사한 활성을 갖는 프로모터일 수 있다. 프로모터는 또한 전사활성화에 반응성인 요소, 예를 들어 저산소증 반응 요소, Gal4 반응 요소, lac 저해인자 반응 요소, 및 소분자 제어 시스템, 예컨대 테트라시클린-조절된 시스템 및 RU-486 시스템을 포함할 수 있다 (예를 들어, Gossen & Bujard, 1992, Proc. Natl. Acad. Sci. USA, 89:5547; Oligino et al., 1998, Gene Ther., 5:491-496; Wang et al., 1997, Gene Ther., 4:432-441; Neering et al., 1996, Blood, 88:1147-55; 및 Rendahl et al., 1998, Nat. Biotechnol., 16:757-761 참고).
프로모터 이외에도, 전형적으로 발현 벡터는 원핵세포 또는 진핵세포인 숙주 세포에서 핵산 발현을 위해 필요한 모든 추가의 요소를 함유하는 전사 유닛 또는 발현 카세트를 함유한다. 따라서, 전형적인 발현 카세트는 예를 들어 Cas9 변이체를 코딩하는 핵산 서열에 작동가능하게 연결된 프로모터, 및 예를 들어 전사체의 효율적인 폴리아데닐화, 전사 종결, 리보솜 결합 부위, 또는 번역 종결을 위해 필요한 임의의 신호를 함유한다. 카세트의 추가의 요소에는 예를 들어 인핸서 및 슬라이싱된 이종의 인트론 신호가 포함될 수 있다.
유전자 정보를 세포에 전달하기 위한 특정한 발현 벡터는 Cas9 변이체의 의도된 용도, 예를 들어 식물, 동물, 박테리아, 진균, 원생동물 등에서의 발현과 관련하여 선택된다. 표준 박테리아 발현 벡터에는 플라스미드, 예컨대 pBR322 기재 플라스미드, pSKF, pET23D, 및 상업적으로 입수가능한 태그-융합 발현 시스템, 예컨대 GST 및 LacZ가 포함된다.
진핵세포 바이러스로부터의 조절 요소를 함유하는 발현 벡터는 종종 진핵세포 발현 벡터, 예를 들어 SV40 벡터, 유두종 바이러스 벡터, 및 엡스테인-바르(Epstein-Barr) 바이러스로부터 유래된 벡터에서 사용된다. 다른 예시적인 진핵세포 벡터에는 pMSG, pAV009/A+, pMTO10/A+, pMAMneo-5, 바쿨로바이러스 pDSVE, 및 SV40 초기 프로모터, SV40 후기 프로모터, 메탈로티오네인 프로모터, 쥐 유방 종양 바이러스 프로모터, 라우스 육종 바이러스 프로모터, 폴리헤드린 프로모터, 또는 진핵 세포에서의 발현에 효과적인 것으로 제시된 프로모터의 지시 하에 단백질 발현을 허용하는 임의의 다른 벡터가 포함된다.
Cas9 변이체를 발현하기 위한 벡터는 가이드 RNA의 발현을 유도하기 위한 RNA Pol III 프로모터, 예를 들어 H1, U6 또는 7SK 프로모터를 포함할 수 있다. 이들 인간 프로모터는 플라스미드 형질감염 이후 포유동물 세포에서 Cas9 변이체의 발현을 허용한다.
일부 발현 시스템은 안정하게 형질감염된 세포주의 선택을 위한 마커, 예컨대 티미딘 키나제, 히그로마이신 B 포스포트랜스퍼라제, 및 디히드로폴레이트 리덕타제를 갖는다. 폴리헤드린 프로모터 또는 다른 강력한 바쿨로바이러스 프로모터의 지시 하에 gRNA 코딩 서열과 함께 곤충 세포에서 바쿨로바이러스 벡터를 사용하는 것과 같은 고수율 발현 시스템 또한 적합하다.
발현 벡터에 전형적으로 포함되는 요소에는 또한 이. 콜라이에서 기능하는 레플리콘, 재조합 플라스미드를 보유하는 박테리아의 선택을 허용하기 위해 항생제 내성을 코딩하는 유전자, 및 재조합 서열의 삽입을 허용하기 위해 플라스미드의 비필수 영역에서의 독특한 제한 부위를 포함한다.
표준 형질감염 방법을 이용하여 다량의 단백질을 발현하는 박테리아, 포유동물, 효모 또는 곤충 세포주를 생성한 다음, 표준 기술을 이용하여 정제한다 (예를 들어, Colley et al., 1989, J. Biol. Chem., 264:17619-22; Guide to Protein Purification, in Methods in Enzymology, vol. 182 (Deutscher, ed., 1990) 참고). 진핵 및 원핵 세포의 형질전환은 표준 기술에 따라 수행한다 (예를 들어, Morrison, 1977, J. Bacteriol. 132:349-351; Clark-Curtiss & Curtiss, Methods in Enzymology 101:347-362 (Wu et al., eds, 1983) 참고).
외래 뉴클레오티드 서열을 숙주 세포에 도입하는 임의의 공지된 절차를 이용할 수 있다. 이들 절차는 인산칼슘 형질감염, 폴리브렌, 원형질체 융합, 전기천공, 뉴클레오펙션, 리포좀, 현미주사, 네이키드 DNA, 플라스미드 벡터, 바이러스 벡터, 에피좀형 및 편입형 둘 다, 및 클로닝된 게놈 DNA, cDNA, 합성 DNA 또는 다른 외래 유전자 물질을 숙주 세포에 도입하기 위한 다른 널리 공지된 방법의 이용을 포함한다 (예를 들어, 상기 Sambrook et al. 참고). 이용된 특정한 유전자 조작 절차는 Cas9 변이체를 발현할 수 있는 숙주 세포에 적어도 하나의 유전자를 성공적으로 도입할 수 있어야만 한다.
본 발명은 벡터 및 상기 벡터를 포함하는 세포를 포함한다.
실시예
본 발명은 하기 실시예에서 추가로 기재되며, 하기 실시에는 청구항에 기재된 본 발명의 범위를 제한하지 않는다.
방법
실시예 1 및 2에서 하기 물질 및 방법이 사용되었다.
플라스미드 및 올리고뉴클레오티드
이 연구에서 사용된 개략적 맵 및 DNA 서열은 도 5A-J 및 서열식별번호:7-20에서 확인할 수 있다. 양성 선택 플라스미드, 음성 선택 플라스미드, 및 부위-고갈 라이브러리를 생성하기 위해 사용된 올리고뉴클레오티드의 서열은 표 1에 기재하였다. 이 연구에서 모든 gRNA 표적의 서열은 표 2에 기재하였다. Cas9에서의 점 돌연변이는 PCR에 의해 생성하였다.
Figure pct00009
Figure pct00010
Figure pct00011
Figure pct00012
Figure pct00013
Figure pct00014
박테리아 Cas9/sgRNA 발현 플라스미드는 Cas9 및 sgRNA를 별도로 발현시키기 위해 2가지 T7 프로모터를 이용하여 제작하였다. 이들 플라스미드는 에스. 피오게네스에 대한 Cas9의 인간 코돈 최적된 변이체 (BPK764, JDS246으로부터 서브클로닝된 SpCas9 서열17), CRISPR 좌위 1로부터의 에스. 써모필루스 Cas9 (MSP1673, 이전에 공개된 명세서로부터 변형된 St1Cas9 서열20), 및 에스. 아우레우스 (BPK2101, 유니프롯(Uniprot) J7RUA5로부터 최적화된 SaCas9 서열 코돈)를 코딩한다. SpCas934, 35 및 St1Cas920의 경우에는 이전에 제조된 sgRNA 서열을 사용한 반면에, SaCas9 sgRNA 서열은, CRISPRfinder를 이용하여 crRNA 반복부에 대한 유럽 뉴클레오티드 보관소(European Nucleotide Archive) 서열 HE980450을 검색하고, 이전에 기재된 것과 유사한 생물정보 접근법을 이용하여 tracrRNA를 확인함으로써 결정하였다36. sgRNA의 스페이서 상보성 영역을 완성하기 위한 어닐링된 올리고를 BsaI cut BPK764 및 BPK2101, 또는 BspMI cut MSP1673에 라이게이션시켰다 (상부 올리고를 생성하기 위해 5'-ATAG를 스페이서에 부착시키고, 하부 올리고를 생성하기 위해 5'-AAAC를 스페이서 서열의 역 보체에 부착시킴).
뮤타짐(Mutazyme) II (애질런트 테크놀로지즈(Agilent Technologies))를 이용하여 SpCas9의 잔기 1097-1368을 ~5.2 치환/킬로베이스로 무작위로 돌연변이시켜, 돌연변이된 PAM-상호작용 (PI) 도메인 라이브러리를 생성하였다. 각각의 PI 도메인 라이브러리의 이론적 복잡도는 수득한 형질전환체의 개수를 기준으로 107 클론 초과로 추정되었다. 어닐링된 표적 부위 올리고를 각각 XbaI/SphI 또는 EcoRI/SphI cut p11-lacY-wtx117에 라이게이션시킴으로써 양성 및 음성 선택 플라스미드를 생성하였다.
2가지 무작위화된 PAM 라이브러리 (각각 상이한 프로토스페이서 서열을 가짐)는, 프로토스페이서의 3' 말단에 바로 인접한 6개의 무작위화된 뉴클레오티드를 함유한 올리고의 하부 가닥을 채우기 위해 Klenow(-exo)를 이용하여 제작하였다 (표 1 참고). 이중-가닥 생성물을 EcoRI에 의해 절단하여, cut p11-lacY-wtx1에 라이게이션하기 위해 EcoRI/SphI 말단을 남겼다. 각각의 무작위화된 PAM 라이브러리의 이론적 복잡도는 수득한 형질전환체의 개수를 기준으로 106 초과로 추정되었다.
SpCas9 및 SpCas9 변이체를 JDS246으로부터 유래된 벡터로부터의 인간 세포에서 발현시켰다16. St1Cas9 및 SaCas9의 경우, MSP1673 및 BPK2101로부터의 Cas9 ORF를 CAG 프로모터 벡터에 서브클로닝하여, 각각 MSP1594 및 BPK2139를 생성하였다. sgRNA의 U6 발현을 위한 플라스미드 (여기에 목적하는 스페이서 올리고를 클로닝할 수 있음)는 SpCas9 sgRNA (BPK1520), St1Cas9 sgRNA (BPK2301) 및 SaCas9 gRNA (VVT1)에 대해 상기 기재된 sgRNA 서열을 이용하여 생성하였다. sgRNA의 스페이서 상보성 영역을 완성하기 위한 어닐링된 올리고를 이들 벡터의 BsmBI 오버행에 라이게이션시켰다 (상부 올리고를 생성하기 위해 5'-CACC를 스페이서에 부착시키고, 하부 올리고를 생성하기 위해 5'-AAAC를 스페이서 서열의 역 보체에 부착시킴).
SpCas9 변이체의 진화를 위한 박테리아-기재 양성 선택 검정
양성 선택 플라스미드 (매입된 표적 부위를 가짐)를 함유하는 적격 이. 콜라이 BW25141(λDE3)23을 Cas9/sgRNA-코딩 플라스미드로 형질전환시켰다. SOB 배지에서 60 분 회복시킨 후, 형질전환체를 클로람페니콜 (비-선택적) 또는 클로람페니콜 + 10 mM 아라비노스 (선택적)를 함유하는 LB 플레이트 상에 플레이팅하였다. 양성 선택 플라스미드의 분할은 생존 빈도: (선택적 플레이트 상의 콜로니 / 비-선택적 플레이트 상의 콜로니)를 계산함으로써 추정하였다 (도 12 또한 참고).
신규한 PAM을 분할할 수 있는 SpCas9 변이체를 선택하기 위해, PI-도메인 돌연변이된 Cas9/sgRNA 플라스미드 라이브러리를, 표적 부위 + 관심 PAM을 코딩하는 양성 선택 플라스미드를 함유하는 이. 콜라이 BW25141(λDE3) 세포로 전기천공시켰다. 일반적으로, ~50,000개 클론을 스크리닝하여, 50 내지 100개 생존자를 수득하였다. 생존 클론의 PI 도메인을 새로운 백본 플라스미드에 서브클로닝하고, 양성 선택을 위해 재시험하였다. 활성에 대한 이러한 이차 스크린에서 10% 초과의 생존을 갖는 클론을 시퀀싱하였다. 시퀀싱된 클론에서 관찰된 돌연변이를, 생존 클론에서 그의 빈도, 치환 유형, SpCas9/sgRNA 결정 구조에서 PAM 염기와의 근접성 (PDB:4UN3)14, 및 (일부 경우에) 인간 세포-기재 EGFP 파괴 검정에서의 활성을 기준으로 하는 추가의 평가를 위해 선택하였다.
Cas9 PAM 특이성을 프로파일링하기 위한 박테리아-기재 부위-고갈 검정
Cas9/sgRNA 발현 플라스미드를 함유하는 적격 이. 콜라이 BW25141(λDE3)을 분할가능한 또는 분할가능하지 않은 표적 부위를 보유한 음성 선택 플라스미드로 형질전환시켰다. SOB 배지에서 60 분 회복시킨 후, 형질전환체를 클로람페니콜 + 카르베니실린을 함유하는 LB 플레이트 상에 플레이팅하였다. 음성 선택 플라스미드의 분할은 형질전환된 DNA μg당 콜로니 형성 유닛을 계산함으로서 추정하였다 (도 13 또한 참고).
음성 선택을 조정하여, 각각의 무작위화된 PAM 라이브러리를 적절한 Cas9/sgRNA 플라스미드를 이미 보유한 이. 콜라이 BW25141(λDE3) 세포에 전기천공시킴으로써 Cas9 뉴클레아제의 PAM 특이성 프로파일을 결정하였다. 80,000-100,000개 콜로니를 LB + 클로람페니콜 + 카르베니실린 플레이트 상에 저밀도 도포로 플레이팅하였다. Cas9에 의한 분할에 불응성인 음성 선택 플라스미드를 함유하는 생존 콜로니를 수확하고, 플라스미드 DNA를 맥시-프렙(maxi-prep, 퀴아젠(Qiagen))에 의해 단리하였다. 생성된 플라스미드 라이브러리를 퓨젼 핫-스타트 플렉스(Phusion Hot-start Flex) DNA 폴리머라제 (뉴 잉글랜드 바이오랩스(New England BioLabs))를 사용하여 PCR에 의해 증폭시킨 다음, 아젠코트 앰퓨어(Agencourt Ampure) XP 클린업 스텝 (베크만 코울터 게노믹스(Beckman Coulter Genomics))을 수행하였다. 각각의 부위-고갈 실험에서 ~500 ng의 클린 PCR 생성물로부터 KAPA HTP 라이브러리 제조 키트 (카파 바이오시스템즈(KAPA BioSystems))를 사용하여 듀얼-인덱스드 Tru-Seq 일루미나(Dual-indexed Tru-Seq Illumina) 심층-시퀀싱 라이브러리를 제조하였다. 다나-파버 캔서 인스티튜트 몰레큘라 바이올로지 코어(Dana-Farber Cancer Institute Molecular Biology Core)는 일루미나 MiSeq 시퀀서(Illumina MiSeq Sequencer) 상에서 150-bp 쌍형성-말단 시퀀싱을 수행하였다.
각각의 MiSeq 작동에 대해 산출한 미가공 FASTQ 파일을 파이톤(Python) 프로그램을 이용하여 분석하여, 상대적인 PAM 고갈을 결정하였다. 프로그램 (방법 참고)을 다음과 같이 작동시켰다: 먼저, 주어진 실험에 대한 모든 FASTQ 리드 파일을 선택할 수 있는 사용자에게 파일 다이얼로그를 제시하였다. 이들 파일에 대해, 각각의 FASTQ 엔트리를 양쪽 가닥 상의 고정된 스페이서 영역에 대해 스캐닝하였다. 스페이서 영역이 발견된 경우에는, 스페이서 영역을 플랭킹하는 6개의 가변 뉴클레오티드를 포획하여 카운터에 넣었다. 검출된 가변 영역의 상기 세트로부터, 각각의 가능한 위치에서 2-6 nt 길이의 각각의 윈도우의 카운트 및 빈도를 표로 작성하였다. 선택후 PAM 고갈 값 (PPDV: 선택된 집단에서의 PAM의 선택후 빈도를 PAM의 선택전 라이브러리 빈도로 나눔)을 계산함으로써, 무작위화된 PAM 라이브러리 둘 다에 대한 부위-고갈 데이터를 분석하였다. 각각의 실험에 대해 6 bp 무작위화된 영역에서 모든 가능한 2-6 길이 윈도우에 걸쳐 PPDV 분석을 수행하였다. PAM 선호도를 가시화하기 위해 본 발명자들이 사용한 윈도우는 야생형 및 변이체 SpCas9 실험에서 제2, 제3 및 제4 PAM 위치를 나타내는 3 nt 윈도우, 및 St1Cas9 및 SaCas9에서 제3, 제4, 제5, 제6 PAM 위치를 나타내는 4 nt 윈도우였다.
PPDV에 대한 2가지 유의성 역가는 다음을 기준으로 결정하였다: 1) 선택전 라이브러리 로그 판독 카운트 비에 대한 dCas9 분포를 기준으로 하는 통계적 유의성 역가 (도 13c & 13d 참고), 및 2) 인간 세포에서 고갈 값과 활성 사이의 실험 관계식을 기준으로 하는 생물학적 활성 역가. 통계적 역가는 dCas9에 대한 평균 PPDV로부터의 3.36 표준 편차 (0.85의 상대적 PPDV와 동등함)로 설정하였고, 이는 다중 비교를 위해 조정한 후 0.05의 정규 분포 양측 p-값 (즉, p=0.05/64)에 상응하였다. 고갈 수준은 인간 세포에서 활성의 합리적인 예측변수로서 작용하기 때문에, 생물학적 활성 역가를 5배 고갈 (0.2의 PPDV와 동등함)로 설정하였다 (도 14 또한 참고). 도 14에서 95% 신뢰 구간은 평균의 표준 편차를 샘플 크기의 제곱근에 1.96을 곱한 값으로 나눔으로써 계산하였다.
인간 세포 배양 및 형질감염
구성적으로 발현된 EGFP-PEST 리포터 유전자의 단일 통합 카피를 보유하는 U2OS.EGFP 세포15를 10% FBS, 2 mM GlutaMax (라이프 테크놀로지즈(Life Technologies)), 페니실린/스트렙토마이신, 및 400 μg/ml의 G418로 보충된 어드밴스드(Advanced) DMEM 배지 (라이프 테크놀로지즈)에서 37℃에서 5% CO2 하에 배양시켰다. 세포를 제조자의 프로토콜에 따라 론자(Lonza) 4D-뉴클레오펙터의 DN-100 프로그램을 사용하여 750 ng의 Cas9 플라스미드 및 250 ng의 sgRNA 플라스미드 (달리 언급하지 않는다면)로 공동-형질감염시켰다. 빈 U6 프로모터 플라스미드와 함께 형질감염된 Cas9 플라스미드를 모든 인간 세포 실험에서 음성 대조군으로서 사용하였다. 내인성 유전자 실험에서 표적 부위는 야생형 SpCas9에 의해 분할가능한 200 bp의 NGG 부위 내에서 선택하였다 (도 16a 및 표 2 참고).
제브라피쉬 관리 및 주사
제브라피쉬 관리 및 사용은 연구 동물 관리에 대한 메사추세츠주 종합 병원 소위원회(Massachusetts General Hospital Subcommittee on Research Animal Care)에 의해 승인받았다. 이전에 기재된 바와 같이 mMESSAGE mMACHINE T7 ULTRA 키트 (라이프 테크놀로지즈)를 사용하여 Cas9 mRNA를 PmeI-소화된 JDS246 (야생형 SpCas9) 또는 MSP469 (VQR 변이체)에 의해 전사시켰다21. 이 연구에서 모든 sgRNA를 클로닝-비의존성 sgRNA 생성 방법에 따라 제조하였다24. sgRNA를 MEGAscript SP6 전사 키트 (라이프 테크놀로지즈)에 의해 전사시키고, RNA 클린 & 컨센트레이터-5 (RNA Clean & Concentrator-5, 자이모 리서치(Zymo Research))에 의해 정제하고, RNase-무함유 물로 용리시켰다.
sgRNA- 및 Cas9-코딩 mRNA를 1-세포 단계 제브라피쉬 배아에 공동-주사하였다. 각각의 배아를 30 ng/μL gRNA 및 300 ng/μL Cas9 mRNA를 함유하는 ~2-4.5 nL 용액으로 주사하였다. 다음 날, 주사된 배아를 정상 형태학적 발달에 대해 입체경 하에 검사하고, 5 내지 9개 배아로부터 게놈 DNA를 추출하였다.
인간 세포 EGFP 파괴 검정
EGFP 파괴 실험은 이전에 기재된 바와 같이 수행하였다16. 형질감염된 세포를 포르테싸(Fortessa) 유세포 분석기 (비디 바이오사이언시즈(BD Biosciences))를 사용하여 형질감염 ~52 시간 후에 EGFP 발현에 대해 분석하였다. 백그라운드 EGFP 손실은 모든 실험에서 대략 2.5%이었다 (그래프에서 적색 점선으로 나타냄).
뉴클레아제-유도된 돌연변이율을 정량화하기 위한 T7E1 검정, 표적화된 심층-시퀀싱, 및 GUIDE-seq
인간 세포15 및 제브라피쉬21에 대해 이전에 기재된 바와 같이 T7E1 검정을 수행하였다. U2OS.EGFP 인간 세포의 경우, 아젠코트 디엔어드밴스(Agencourt DNAdvance) 게놈 DNA 단리 키트 (베크만 코울터 게노믹스)를 사용하여 형질감염 ~72 시간 후에 형질감염된 세포로부터 게놈 DNA를 추출하였다. 제브라피쉬 또는 인간 세포 게놈 DNA로부터의 표적 좌위를 표 1에 열거된 프라이머를 사용하여 증폭시켰다. 대략 200 ng의 정제된 PCR 생성물을 변성시키고, 어닐링시키고, T7E1 (뉴 잉글랜드 바이오랩스)로 소화시켰다. 돌연변이 유발 빈도는 인간 세포15 및 제브라피쉬21에 대해 이전에 기재된 바와 같이 퀴악셀(Qiaxcel) 모세관 전기영동 장비 (퀴아젠)를 사용하여 정량화하였다.
표적화된 심층-시퀀싱의 경우, 이전에 특성분석된 온- 및 오프-타겟 부위 (Tsai et al., Nat Biotechnol 33, 187-197 (2015); Fu et al., Nat Biotechnol 31, 822-826 (2013); Fu et al., Nat Biotechnol 32, 279-284 (2014))를 표 1에 열거된 프라이머와 함께 퓨젼 핫-스타트 플렉스를 사용하여 증폭시켰다. 게놈 좌위를 대조군 조건 (빈 sgRNA), 야생형, 및 D1135E SpCas9에 대해 증폭시켰다. 라이브러리 제조에 대한 각각의 조건으로부터 ~500 ng의 DNA를 풀링하기 전에 아젠코트 앰퓨어 XP 클린업 스텝 (베크만 코울터 게노믹스)을 수행하였다. KAPA HTP 라이브러리 제조 키트 (카파 바이오시스템즈)를 사용하여 듀얼-인덱스드 Tru-Seq 일루미나 심층-시퀀싱 라이브러리를 생성하였다. 다나-파버 캔서 인스티튜트 몰레큘라 바이올로지 코어는 일루미나 MiSeq 시퀀서 상에서 150-bp 쌍형성-말단 시퀀싱을 수행하였다. 표적화된 심층-시퀀싱 데이터의 돌연변이 분석을 이전에 기재된 바와 같이 수행하였다 (Tsai et al., Nat Biotechnol 32, 569-576 (2014)). 간략히, 일루미나 MiSeq 쌍형성 말단 판독 데이터를 bwa를 사용하여 인간 게놈 기준 GRChr37에 맵핑하였다 (Li et al., Bioinformatics 25, 1754-1760 (2009)). 표적 또는 오프-타겟 부위와 중복되는 indel 돌연변이에 대해 고품질 판독 (품질 점수 >= 30)을 평가하였다. 1-bp indel 돌연변이가 1-bp의 예상된 절단점 내에서 발생하지 않는다면, 상기 돌연변이는 분석으로부터 제외하였다. D1135E와 야생형 SpCas9를 비교하는 온- 및 오프-타겟 부위에서 활성의 변화는 양쪽 조건으로부터의 indel 빈도를 비교함으로써 계산하였다 (백그라운드 대조군 앰플리콘 indel 수준을 초과하는 돌연변이율의 경우).
GUIDE-seq 실험을 이전에 기재된 바와 같이 수행하였다 (Tsai et al., Nat Biotechnol 33, 187-197 (2015)). 간략히, 포스포릴화된 포스포로티오에이트-변형된 이중-가닥 올리고데옥시뉴클레오티드 (dsODN)를 상기 기재된 바와 같이 Cas9 뉴클레아제를 이용하여 Cas9 및 sgRNA 발현 플라스미드와 함께 U2OS 세포로 형질감염시켰다. DSB 활성을 함유하는 게놈 간격을 확인하기 위해 dsODN-특이적 증폭, 고산출량 시퀀싱, 및 맵핑을 수행하였다. 야생형 대 D1135E 실험의 경우, 오프-타겟 판독 카운트를 온-타겟 판독 카운트에 대해 정규화하여, 샘플간의 시퀀싱 깊이 차이에 대해 보정하였다. 이어서, 야생형 및 D1135E SpCas9의 정규화 비를 비교하여, 오프-타겟 부위에서 활성의 배수-변화를 계산하였다. GUIDE-seq에 대한 야생형 및 D1135E 샘플이 의도된 표적 부위에서 유사한 올리고 태그 통합률을 가졌는지 여부를 결정하기 위해, 표 1에 열거된 프라이머를 사용하여 100 ng의 게놈 DNA (상기 기재된 바와 같이 단리됨)로부터 퓨젼 핫-스타트 플렉스에 의해 의도된 표적 좌위를 증폭시킴으로써 제한 단편 길이 다형 (RFLP) 검정을 수행하였다. 아젠코트 앰퓨어 XP 키트를 사용하여 클린업하기 전에, 37℃에서 3 시간 동안 대략 150 ng의 PCR 생성물을 20 U의 NdeI (뉴 잉글랜드 바이오랩스)에 의해 소화시켰다. RFLP 결과를 퀴악셀 모세관 전기영동 장비 (퀴아젠)에 의해 대략적인 올리고 태그 통합률을 정량화하였다. 상기 기재된 바와 같이 유사한 목적을 위해 T7E1 검정을 수행하였다.
소프트웨어 - PAM 고갈 MiSeq 데이터를 분석용
명령어 "python PAM_depletion.py"를 사용하여 (파일이 들어있는 디렉토리에서) 명령 프롬프트로 실행
Figure pct00015
Figure pct00016
Figure pct00017
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Figure pct00019
실시예 1
표적화 범위 제한을 다루는 잠재적인 한 방안은 신규한 PAM 특이성을 갖는 Cas9 변이체를 조작하는 것이다. PAM 특이성을 변경시키기 위한 이전의 시도에서는, 제2 및 제3 PAM 위치에서 구아닌 뉴클레오티드와 접촉하는 아르기닌 잔기 (각각 R1333 및 R1335)를 돌연변이시키는 염기-특이적 SpCas9-PAM 상호작용에 대한 구조적 정보를 이용하였다 (Anders et al., Nature 513, 569-573 (2014)). 양쪽 아르기닌의 글루타민으로의 치환 (그의 측쇄는 아데닌과 상호작용하는 것으로 예상될 수 있음)은, 시험관내에서 예상된 NAA PAM을 보유하는 표적을 분할할 수 있는 SpCas9 변이체를 생성하는데 실패하였다 (Anders et al., Nature 513, 569-573 (2014)). 본 발명자들은, 뉴클레아제 유도된 indel이 형광 손실을 초래하는 인간 세포-기재 U2OS EGFP 리포터 유전자 파괴 검정을 이용하여 (Reyon et al., Nat Biotechnol 30, 460-465 (2012); Fu et al., Nat Biotechnol 31, 822-826 (2013)), R1333Q/R1335Q SpCas9 변이체가 NAA PAM을 갖는 표적 부위를 효율적으로 분할하는데 실패하였음을 확인하였다 (도 1a). 추가로, 본 발명자들은 단일 R1333Q 및 R1335Q SpCas9 변이체 각각이 그들의 예상된 NAG 및 NGA 부위 각각을 갖는 표적 부위를 효율적으로 분할하는데 실패하였음을 확인하였다 (도 1a). 따라서, 본 발명자들은 재조작 PAM 특이성이 R1333 및 R1335 이외의 위치에서 추가의 돌연변이를 필요로 할 수 있는 것으로 판단하였다. 예를 들어, 입수가능한 구조적 정보는, K1107 및 S1136이 각각 PAM의 제2 및 제3 염기와 직접적인 또는 간접적인 작은 홈 접촉을 만든다는 것을 제시한다 (Anders et al., Nature 513, 569-573 (2014)). 따라서, 이들 위치에서 또는 근처에서의 추가의 변경이 PAM 특이성을 변경시키는데 필요할 수 있다는 것이 타당하다.
PAM 특이성을 변형시키는데 결정적일 수 있는 추가의 위치를 확인하기 위해, 본 발명자들은 귀소 엔도뉴클레아제의 특성을 연구하기 위해 이전에 사용된 박테리아 선택 시스템 (이후 양성 선택이라고 지칭함)을 이용하였다 (Chen & Zhao, Nucleic Acids Res 33, e154 (2005); Doyon et al., J Am Chem Soc 128, 2477-2484 (2006)). 이 시스템에 대한 본 발명자들의 조정에서, 유도성 독성 유전자를 코딩하는 양성 선택 플라스미드의 Cas9-매개된 분할은 선형화된 플라스미드의 후속적인 분해 및 손실로 인해 세포 생존을 가능하게 한다 (도 1b 및 도 12a). SpCas9가 양성 선택 시스템에서 기능할 수 있음을 수립한 후에, 본 발명자들은 야생형 및 R1335Q 변이체 둘 다가 NGA PAM을 갖는 표적 부위를 보유하는 선택 플라스미드를 분할하는 그들의 능력에 대해 시험하였고, 예상된 대로 생존을 관찰하는데 실패하였다 (도 12a). 기능-획득 돌연변이에 대해 스크리닝하기 위해, 본 발명자들은 5.2 돌연변이/킬로베이스의 평균 돌연변이율로 무작위로 돌연변이된 PAM-상호작용 도메인 (아미노산 위치 1097-1368)을 보유하는 야생형 및 R1335Q SpCas9의 라이브러리를 생성하였다 (도 12b 및 방법). 이들 라이브러리를, NGA PAM을 갖는 표적 부위를 함유하는 양성 선택 플라스미드를 갖는 박테리아에 도입시키고, 선택적 배지 상에 플레이팅하였다. R1335Q-기재 라이브러리로부터의 생존 클론의 서열로부터, 기존의 R1335Q 돌연변이 이외의 가장 빈번한 치환이 D1135V/Y/N/E 및 T1337R임이 드러났다 (표 3). 본 발명자들은 야생형 SpCas9-기재 라이브러리 선택을 갖는 생존자를 더 적게 수득하였지만, 이들 클론의 서열 또한 D1135V/Y/N 및 R1335Q 돌연변이를 포함하였다. 다음으로, 본 발명자들은 인간 세포-기재 EGFP 파괴 검정을 이용하여 D1135V/Y/N/E, R1335Q, 및 T1337R 돌연변이의 가능한 모든 단일, 이중 및 삼중 조합을 보유하는 SpCas9를 조립하여 시험하였다. 이 분석은 3개의 모든 위치에서 치환을 갖는 SpCas9 변이체가 NGA PAM에 대해 최고 활성을 나타내었지만, NGG PAM에 대해서는 최저 활성을 나타내었음이 제시하였다 (도 1c). 본 발명자들은 추가의 특성분석을 위해 2가지 SpCas9 변이체, D1135V/R1335Q/T1337R 및 D1135E/R1335Q/T1337R (이후 각각 VQR 및 EQR SpCas9 변이체라고 지칭함)을 선택하였는데, 이들이 NGA와 NGG PAM 사이의 가장 큰 차이를 가졌기 때문이다 (도 1c).
본 발명자들의 신규한 SpCas9 변이체에 대한 전반적인 PAM 특이성 프로파일을 평가하기 위해, 본 발명자들은 박테리아-기재 음성 선택 시스템을 이용하였다 (도 1d 및 도 13a). 이전의 연구에서는 Cas9 뉴클레아제의 분할 부위 선호도를 확인하기 위해 유사한 유형의 선택 시스템을 이용하였다 (Jiang et al., Nat Biotechnol 31, 233-239 (2013); Esvelt et al., Nat Methods 10, 1116-1121 (2013)). 이 검정의 본 발명자들의 버전에서 (본 발명자들은 부위-고갈 검정이라고 지칭함), 프로토스페이서에 인접하여 위치한 무작위화된 6 bp 서열을 보유하는 플라스미드의 라이브러리를 이. 콜라이에서 Cas9/sgRNA 복합체에 의한 분할에 대해 시험하였다 (도 13b). Cas9/sgRNA 복합체에 의한 분할에 대해 내성인 프로토스페이서-인접 서열을 갖는 플라스미드는 항생제 내성 유전자의 존재로 인해 세포 생존을 가능하게 하는 반면에, 분할가능한 서열을 보유하는 플라스미드는 분해되어 라이브러리로부터 고갈되었다 (도 13b). ~100,000의 표적화될 수 없는 서열의 고산출량 시퀀싱은 임의의 주어진 PAM에 대한 선택후 PAM 고갈 값 (PPDV)의 계산을 가능하게 하였다. PAM (또는 PAM의 군)의 PPDV는, 선택후 집단에서의 해당 PAM 빈도를 선택전 라이브러리에서의 그의 빈도로 나눔으로써 정의된다. 이 정량적인 값은 해당 PAM에 대한 Cas9 활성의 추정치를 제공한다. 2가지 무작위화된 PAM 라이브러리 (각각 상이한 프로토스페이서를 가짐)에 대해 촉매 불활성 Cas9 (dCas9)에 의해 수득된 프로파일은, 임의의 주어진 PAM 또는 PAM의 군에 대한 PPDV의 통계적으로 유의한 변화를 나타내는 것의 정의를 가능하게 한다 (도 13c). 이어서, 본 발명자들은 2가지 무작위화된 PAM 라이브러리를 이용하여 수득한 야생형 SpCas9에 대한 PPDV가 표적화가능한 PAM의 이전에 기재된 그의 프로파일을 재연하였음을 입증함으로써 본 발명자들의 부위-고갈 검정을 인증하였다 (Jiang et al., Nat Biotechnol 31, 233-239 (2013)) (도 1e).
부위-고갈 검정을 이용하여, 본 발명자들은 2가지 무작위화된 PAM 라이브러리를 사용하여 VQR 및 EQR SpCas9 변이체에 대한 PAM 특이성 프로파일을 수득하였다. VQR 변이체는 NGAN 및 NGCG PAM을 보유하는 부위를 강력하게 고갈시키고, NGGG, NGTG 및 NAAG PAM을 보유하는 부위는 보다 약하게 고갈시켰다 (도 1f). 대조적으로, EQR 변이체는 NGAG PAM을 강력하게 고갈시키고, NGAT, NGAA 및 NGCG PAM은 보다 약하게 고갈시켰으며 (도 1f), 이는 VQR 변이체에 대한 잠재적으로 더욱 제한된 표적화 범위를 입증한다. 부위-고갈 검정에 의해 확인된 PAM이 또한 인간 세포에서 인식될 수 있는지 여부를 시험하기 위해, 본 발명자들은 EGFP 파괴 검정을 이용하여 표적 부위에 대한 VQR 및 EQR SpCas9 변이체에 의한 분할을 평가하였다. VQR 변이체는 NGAN PAM을 보유하는 EGFP의 부위를 강력하게 분할하였고 (NGAG>NGAT=NGAA>NGAC의 상대적인 효율성으로), 또한 NGCG, NGGG 및 NGTG PAM을 보유하는 부위를 전반적으로 보다 낮은 효율로 분할하였다 (도 1g). EQR 변이체는 또한, 모두 VQR 변이체에 비해 더 낮은 활성으로, 인간 세포에서 다른 NGAN PAM에 비해 NGAG 및 NGNG PAM에 대한 그의 선호도를 재연하였다 (도 1g). 종합하면, 인간 세포에서 이들 결과는, 박테리아 부위-고갈 검정에서 관찰된 것을 강력하게 반영하고 (도 14), 박테리아 검정에서 0.2의 PPDV (5배 고갈을 나타냄)가 인간 세포에서의 활성에 대해 합리적으로 예상되는 역가를 제공함을 시사한다 (도 14).
다음으로, 본 발명자들은 NGC PAM을 인식할 수 있는 SpCas9 변이체를 확인하기 위해 시도함으로써 본 발명자들의 조작 전략의 일반화 가능성을 확장시키고자 하였다. 먼저, 본 발명자들은 시토신과 상호작용할 수 있을 것으로 예상된 R1335의 아미노산 치환 (D, E, S, 또는 T)을 보유한 Cas9 돌연변이체를 고안하였고, 양성 선택 시스템을 이용하여 NGC PAM 부위에 대해 활성을 갖지 않음을 확인하였다. 이어서, 본 발명자들은 이들 단일 치환된 SpCas9 변이체 각각의 PAM-상호작용 도메인을 무작위로 돌연변이시켰지만, 양성 선택에서 생존 콜로니를 수득하는데 여전히 실패하였다. T1337R 돌연변이가 본 발명자들의 VQR 및 EQR SpCas9 변이체의 활성을 증가시켰기 때문에 (도 1c), 본 발명자들은 이 돌연변이를 A, D, E, S, T 또는 V의 R1335 치환과 조합하고, 그들의 PAM-상호작용 도메인을 다시 무작위로 돌연변이시켰다. 이들 6가지 돌연변이된 라이브러리 (기존의 R1335E/T1337R 및 R1335T/T1337R 치환을 보유함) 중 2가지를 이용하는 선택은 다양한 추가의 돌연변이를 보유하는 생존 콜로니를 생성하였다 (표 3). 박테리아 및 인간 세포-기재 검정 둘 다를 이용하는 선택된 다양한 클론의 특성분석은, 특정한 4개 위치에서의 치환 (D1135V, G1218R, R1335E 및 T1337R)이 NGC PAM의 분할에 중요한 것으로 여겨짐을 시사하였다. EGFP 파괴 검정을 이용하는 이들 돌연변이의 모든 잠재적인 단일, 이중, 삼중 및 사중 조합의 조립 및 시험은, 사중 VRER 변이체가 NGCG PAM에 대해 최고 활성을 나타내고, NGGG PAM에 대해 최소 활성을 나타냄을 수립하였다 (도 1h). 부위-고갈 검정을 이용하는 VRER 변이체의 분석은 NGCG PAM에 대해 매우 특이적임이 드러났다 (도 1i). 이 결과와 일치하게, VRER 변이체를 갖는 인간 세포에서 수행한 EGFP 파괴 검정에 의해, NGCG PAM을 갖는 부위의 효율적인 분할, NGCA, NGCC 및 NGCT PAM을 갖는 부위의 크게 감소되고 일관성 없는 분할, 및 NGAG, NGTG 및 NGGG PAM을 갖는 부위에 대한 본질적으로 활성 없음이 드러났다 (도 1j).
본 발명자들의 VQR 및 VRER SpCas9 변이체가 야생형 SpCas9에 의해 현재 변형가능하지 않은 부위의 표적화를 가능하게 할 수 있음을 직접 입증하기 위해, 본 발명자들은 제브라피쉬 배아 및 인간 세포에서 내인성 유전자에 대한 그들의 활성을 시험하였다. 단일 세포 제브라피쉬 배아에서, 본 발명자들은 VQR 변이체가 NGAG PAM을 보유하는 내인성 유전자 부위를 20 내지 43%의 평균 돌연변이 유발 빈도로 효율적으로 변형시킬 수 있고 (도 2a), indel이 예상된 분할 부위에서 기원하였음을 (도 15) 확인하였다. 인간 세포에서, 본 발명자들은 VQR 변이체가 NGAG, NGAT 및 NGAA PAM을 보유한 4가지 상이한 내인성 유전자에 걸쳐 16개 부위를 강력하게 변형시켰음을 확인하였다 (6 내지 53%의 범위, 평균 33%; 도 2b 및 도 16a). 중요하게는, 본 발명자들은 야생형 SpCas9가 제브라피쉬 및 인간 세포에서 NGAG 및 NGAT PAM을 갖는 동일한 부위의 대부분을 효율적으로 변경시킬 수 없었지만 (도 2a 및 2c), NGG PAM을 보유하는 부위는 거의 효율적으로 변형시켰음을 (도 16b) 증명하였다. 유사하게, 3가지 내인성 인간 유전자에 걸쳐 NGCG PAM을 갖는 9개 부위에서 VRER 변이체 활성을 실험하였을 때, 본 발명자들은 강력한 평균 파괴 빈도 (5 내지 36%의 범위, 평균 21%; 도 2d)를 또한 관찰하였다. 본 발명자들의 부위-고갈 데이터와 일치하게 (도 1e & 1f), VQR 변이체는 VRER 변이체에서 관찰된 것과 유사한 효율로 NGCG PAM 부위를 변경시킨 반면에, 야생형 SpCas9는 그러지 못하였다 (도 2d). 기준 인간 게놈 서열의 컴퓨터 분석은, 본 발명자들의 VQR 및 VRER SpCas9 변이체의 추가가 이전에는 야생형 SpCas9만으로 가능했던 것에 비해 잠재적인 표적 부위의 범위를 배가시켰음을 제시한다 (도 2e). 종합하면, 이들 결과는, 본 발명자들의 조작된 SpCas9 변이체가 제브라피쉬 배아 및 인간 세포에서 이전에는 접근불가능했던 내인성 부위의 변형을 가능하게 함으로써 SpCas9의 표적화 범위를 확장시킴을 입증한다.
본 발명자들의 VQR 및 VRER SpCas9 뉴클레아제의 게놈에 걸친 특이성을 결정하기 위해, 본 발명자들은 인간 세포에서 이들 SpCas9 변이체의 오프-타겟 분할 사건을 프로파일링하도록 최근에 기재된 GUIDE-seq (Genome-wide Unbiased Identification of Double-stranded breaks Enabled by sequencing) 방법10을 이용하였다. 본 발명자들은 총 13가지의 상이한 sgRNA를 이용하여 VQR 및 VRER SpCas9 변이체의 게놈에 걸친 활성을 프로파일링하였고 (각각 도 2b 및 2d로부터 VQR에 대해 8가지 및 VRER에 대해 5가지), 이로써 본 발명자들은 그들의 의도된 온-타겟 부위에서 높은 효율을 유도할 수 있음을 제시하였다. 이들 GUIDE-seq 실험은 수많은 중요한 관찰을 생성하였다: 인간 세포에서 본 발명자들의 SpCas9 변이체에 의해 유도된 오프-타겟 DSB의 개수는 야생형 SpCas9에 의해 이전에 관찰된 것에 필적할만하였다 (또는 VRER 변이체의 경우에는 아마도 훨씬 더 양호함) (도 2f). 본 발명자들은 VRER에 의해 관찰된 게놈에 걸친 높은 특이성이 NGCG PAM에 대한 그의 제한된 특이성 및 아마도 인간 게놈에서 NGCG PAM을 갖는 부위의 상대적인 고갈 둘 다에 의해 생성될 수 있음을 주목하였다 (도 2e)21. 추가로, 관찰된 오프-타겟 부위는 1개의 염기에 의해 3'이 "이동된" PAM에 대한 일부 내성을 비롯하여 본 발명자들의 부위-고갈 실험에 의해 예상되는 PAM 서열을 전반적으로 갖는다 (도 1f 및 1i로부터의 PAM을 도 17로부터의 것과 비교함). 최종적으로, 본 발명자들의 VQR 및 VRER SpCas9 변이체의 오프-타겟 부위에서 확인된 미스매치의 위치 및 개수 (도 17)는 본 발명자들은 비-반복성 서열로 표적화된 sgRNA에 대해 야생형 SpCas9에 의해 이전에 관찰한 것과 그들의 분포에 있어서 유사하였다10.
이전의 연구는 SpCas9에 의한 불완전한 PAM 인식은 인간 세포에서 비-표준적인 NAG, NGA 및 다른 PAM을 함유하는 원치않는 부위의 인식을 유도할 수 있음을 제시한 바 있다 (Hsu et al., Nat Biotechnol 31, 827-832 (2013); Tsai et al., Nat Biotechnol 33, 187-197 (2015); Jiang et al., Nat Biotechnol 31, 233-239 (2013); Mali et al., Nat Biotechnol 31, 833-838 (2013); Zhang et al., Sci Rep 4, 5405 (2014)). 따라서, 본 발명자들은 PAM-상호작용을 매개하는 잔기에서 또는 근처에서의 돌연변이가 SpCas9 PAM 특이성을 개선시키는 지에 대해 탐구하는데 관심이 있었다. VQR 변이체를 조작하면서, 본 발명자들은 D1135E SpCas9 돌연변이체가 야생형 SpCas9에 비해 표준적인 NGG PAM과 비-표준적인 NGA PAM을 더 잘 구별하는 것으로 여겨짐을 주목하였다 (도 1c). 이러한 관찰 하에, 본 발명자들의 부위-고갈 검정을 이용하여 본 발명자들은 상기 D1135E 변이체의 PAM 인식 프로파일을 철저히 평가하였다. 이 실험으로부터 야생형 SpCas9에 비해 D1135E SpCas9에 의한 비-표준적인 NAG, NGA 및 NNGG PAM의 고갈이 감소되었음이 드러났다 (도 3a). 흥미롭게는, 이 효과가 본 발명자들이 사용한 2가지 프로토스페이서 중 하나에 대해 더욱 현저하였고, 이는 비-표준적인 PAM 인식에 대한 D1135E 치환의 영향을 프로토스페이서-의존성 방식으로 어느 정도 변화시킬 수 있음을 시시한다. 중요하게는, 본 발명자들은 임의의 새로운 비-표준적인 PAM 특이성의 출현을 관찰하지 않았다.
다음으로, 본 발명자들은 D1135E SpCas9의 개선된 PAM 특이성 또한 인간 세포에서 관찰될 수 있는지 여부를 시험하였다. 비-표준적인 NAG 또는 NGA PAM을 갖는 8개 표적 부위에 대한 야생형 및 D1135E SpCas9의 직접 비교에서, 본 발명자들은 이들 부위가 EGFP 파괴 검정에서 야생형 SpCas9에 의해서 보다 D1135E에 의해 일관되게 덜 효율적으로 분할되는 것으로 관찰하였다 (도 3b, 활성에서 1.94의 평균 배수 감소). 중요하게는, 야생형 및 D1135E SpCas9 둘 다 표준적인 NGG PAM을 갖는 4개의 EGFP 리포터 유전자 부위 및 6개의 내인성 인간 유전자 부위에 대해 필적할만한 활성을 제시하였으며 (각각 도 3b 및 3c), 이는 D1135E 변이체가 NGG PAM을 갖는 온-타겟 부위의 분할에 대해 눈에 띄는 영향을 미치지 않음을 입증한다 (10개의 모든 부위에 걸쳐 활성에서 1.04의 평균 배수 감소). 본 발명자들이 인간 세포에 형질감염된 Cas9-코딩 플라스미드 농도를 감소시킨 적정 실험에서, 동일한 부위로 표적화시킬 때 야생형 및 D1135E SpCas9의 활성에서의 실질적인 차이가 없음이 드러났고 (도 3d), 이는 D1135E 변이체에 의해 관찰된 증가된 특이성이 단순히 단백질 탈안정화의 결과가 아님을 시사한다.
D1135E의 도입이 SpCas9의 오프-타겟 분할 효과를 감소시킬 수 있는지 여부를 더 직접적으로 평가하기 위해, 본 발명자들은 3가지 상이한 sgRNA의 이전에 공지된 25개 오프-타겟 부위에 대해 야생형 및 D1135E SpCas9에 의해 유도된 돌연변이율을 비교하도록 심층-시퀀싱을 이용하였다 (Hsu et al., Nat Biotechnol 31, 827-832 (2013); Tsai et al., Nat Biotechnol 33, 187-197 (2015); Fu et al., Nat Biotechnol 31, 822-826 (2013)). 이들 25개 부위는 스페이서 서열 및 표준적인 NGG 및 비-표준적인 PAM 둘 다에서 다양한 미스매치를 갖는 오프-타겟 부위를 포함하였다 (도 3e). 이들 심층-시퀀싱 실험의 결과에서, D1135E 변이체는 3개의 온-타겟 부위에서 관찰된 돌연변이 빈도에 비해 백그라운드 indel 비율을 초과하는 활성을 갖는 22개의 오프-타겟 부위 중 19개에서 감소된 돌연변이 빈도를 제시함이 드러났다 (도 3e & 3f). 흥미롭게도, 이들 감소된 오프-타겟 돌연변이 빈도는 표준적인 PAM을 갖는 여러 부위에서 관찰되었고, 이는 D1135E에 의한 특이성 증가가 비-표준적인 PAM을 갖는 부위로만 제한되지 않음을 시사한다. 게놈에 걸친 규모로 D1135E와 연관된 특이성에서의 개선을 평가하기 위해, 본 발명자들은 3가지 상이한 sgRNA (이 중 2가지는 표준적인 및 비-표준적인 PAM을 갖는 오프-타겟 부위를 갖는 것으로 이전에 공지된 것임 (Hsu et al., Nat Biotechnol 31, 827-832 (2013); Tsai et al., Nat Biotechnol 33, 187-197 (2015); Fu et al., Nat Biotechnol 31, 822-826 (2013))를 갖는 야생형 및 D1135E SpCas9를 이용하여 GUIDE-seq 실험을 수행하였다. 본 발명자들은 D1135E SpCas9 변이체와 야생형 SpCas9를 비교할 때 게놈에 걸친 특이성에서의 전반적인 개선을 관찰하였다 (도 3g). 본 발명자들이 시험한 3가지 모든 sgRNA의 경우, 특이성에서의 이들 개선은 표준적인 또는 비-표준적인 PAM을 갖는 미스매칭된 스페이서를 함유한 오프-타겟 부위에서 관찰되었다 (도 18). 중요하게는, 이들 GUIDE-seq 실험에 의해, D1135E 돌연변이의 도입이 SpCas9에 의해 유도된 오프-타겟 효과의 개수를 증가시키지 않는 것으로 입증되었다. 종합하면, 이들 결과는 D1135E 치환이 SpCas9의 전반적인 특이성을 증가시킬 수 있음을 제시한다.
상기 기재된 모든 실험에서 SpCas9를 사용하여 수행하였지만, 신규한 PAM 특이성을 갖는 Cas9를 특성분석 및 조작하기 위한 매력적인 후보가 될 수 있는, 다른 박테리아로부터의 여러 Cas9 이종상동유전자가 있다 (Fonfara et al., Nucleic Acids Res 42, 2577-2590 (2014); Ran et al., Nature 520, 186-191 (2015)). 이의 실현가능성을 탐구하기 위해, 본 발명자들은 2가지 유사 크기 이종상동유전자, CRISPR1 좌위로부터의 스트렙토코쿠스 써모필루스 Cas9 (St1Cas9) (Deveau et al., J Bacteriol 190, 1390-1400 (2008); Horvath et al., J Bacteriol 190, 1401-1412 (2008)) 및 스타필로코쿠스 아우레우스 (SaCas9) (Hsu et al., Cell 157, 1262-1278 (2014); Ran et al., Nature 520, 186-191 (2015))가 본 발명자들의 박테리아 선택 검정에서 또한 기능할 수 있는지 여부를 결정하였다. St1Cas9의 PAM은 NNAGAA (서열식별번호:3)로 이전에 특성분석된 반면에 (Esvelt et al., Nat Methods 10, 1116-1121 (2013); Fonfara et al., Nucleic Acids Res 42, 2577-2590 (2014); Deveau et al., J Bacteriol 190, 1390-1400 (2008); Horvath et al., J Bacteriol 190, 1401-1412 (2008)), 이전에 기재된 접근법을 이용하여 SaCas9 PAM의 생물정보를 유도하고자 하는 본 발명자들의 시도는 (Fonfara et al., Nucleic Acids Res 42, 2577-2590 (2014)) 컨센서스 서열을 수득하는데 실패하였다 (데이터는 제시하지 않음). 따라서, 본 발명자들은 SaCas9 및 양성 대조군으로서 St1Cas9에 대한 PAM을 결정하기 위한 본 발명자들의 부위-고갈 검정을 이용하였다. 이들 실험은 2가지 상이한 프로토스페이서, 및 각각의 프로토스페이서에 대해 2가지 상이한 상보성 길이를 갖는 sgRNA를 이용하여 수행하였고, 그 결과 Cas9에 대한 4가지 선택을 수득하였다. St1Cas9의 경우, 본 발명자들은 이전에 기재된 6가지 PAM 이외에 2가지 신규한 PAM을 확인하였다 (Esvelt et al., Nat Methods 10, 1116-1121 (2013); Fonfara et al., Nucleic Acids Res 42, 2577-2590 (2014); Horvath et al., J Bacteriol 190, 1401-1412 (2008)) (도 4a 및 도 19c 및 19d, SaCas9 PAM 특이성의 최근의 정의와 일치함 (Ran et al., Nature 520, 186-191 (2015))). SaCas9의 경우, 주로 하나의 프로토스페이서에 의해 관찰된 제한된 PAM 선호도로 인해 4가지 선택에서 PPDV 가변성이 있었다. 그 결과, 3가지 PAM만이 4가지 모든 실험에서 5배 초과로 고갈되었다: NNGGGT (서열식별번호:4), NNGAAT (서열식별번호:6), NNGAGT (서열식별번호:5) (도 4b). 그러나, 본 발명자들은 제2 프로토스페이서 라이브러리를 이용하여 더욱 표적화가능한 여러 PAM을 확인하였고, 이는 SaCas9가 추가의 수많은 PAM을 인식할 수 있음을 시사한다 (도 18c 및 18d). 본 발명자들의 부위-고갈 실험에서 확인된 PAM을 이용하여 (St1Cas9의 경우 NNAGAA (서열식별번호:3) 및 SaCas9의 경우 NNGAGT (서열식별번호:5)), 본 발명자들은 St1Cas9 및 SaCas9 둘 다 박테리아 양성 선택 시스템에서 효율적으로 기능할 수 있음을 확인하였고 (도 4c), 이는 그들의 PAM 특이성이 돌연변이 유발 및 선택에 의해 변형될 수 있음을 시사한다.
모든 Cas9 이종상동유전자가 그들의 천연 상태 외에서 효율적으로 기능하지는 않기 때문에 (Esvelt et al., Nat Methods 10, 1116-1121 (2013)), 본 발명자들은 St1Cas9 및 SaCas9가 인간 세포에서 표적 부위를 강력하게 분할할 수 있는지 여부를 시험하였다. St1Cas9는 인간 세포에서 뉴클레아제로서 기능하지만 단지 일부 부위에서만 기능하는 것으로 이전에 제시된 바 있다 (Esvelt et al., 2013; Cong et al., Science 339, 819-823 (2013)). 본 발명자들은 가변-길이 상보성 영역을 갖는 sgRNA를 이용하여 NNAGAA (서열식별번호:3) PAM을 보유하는 부위에 대한 St1Cas9 활성을 평가하였고, 5가지 표적 부위 중 3개에서 높은 활성이 확인되었다 (도 4d). SaCas9의 경우, 본 발명자들은 NNGGGT (서열식별번호:4) 또는 NNGAGT (서열식별번호:5) PAM을 보유하는 8가지 부위에서 효율적인 활성을 관찰하였다 (도 4e). St1Cas9 및 SaCas9 둘 다의 경우, 스페이서 상보성의 활성과 길이 사이에 명백한 상관관계가 없음이 관찰되었다 (도 19e). 다음으로, 본 발명자들은 St1Cas9 및 SaCas9가 인간 세포에서 내인성 좌위를 효율적으로 변형시킬 수 있는지 여부를 결정하였다. St1Cas9의 경우, T7E1 검정에 의해 판단되는 바와 같이 4가지 유전자에 걸쳐 11개 부위 중 7개는 효율적으로 파괴된 반면에 (1 내지 25%, 평균 13%; 도 4f), SaCas9는 4가지 유전자에 걸쳐 시험된 16개 부위에서 다소 더 강력한 활성을 나타내었다 (1% 내지 37%, 평균 19%; 도 4g). 다시 한 번, St1Cas9 및 SaCas9의 경우 sgRNA 스페이서 길이를 고려할 때 명백한 경향이 관찰되지 않았다 (도 19f). 종합하면, 본 발명자들의 결과는, St1Cas9 및 SaCas9가 본 발명자들의 박테리아-기재 선택 및 인간 세포 둘 다에서 강력하게 기능함을 제시하였고, 이는 이들이 신규한 PAM 특이성을 갖는 추가의 SpCas9 변이체를 조작하기 위한 매력적인 후보가 되게 한다.
Figure pct00020
Figure pct00021
Figure pct00022
Figure pct00023
Figure pct00024
Figure pct00025
Figure pct00026
실시예 2. 스타필로코쿠스 아우레우스 Cas9의 PAM 특이성의 조작
본 발명자들은 스트렙토코쿠스 피오게네스 Cas9 (SpCas9)의 잔기 (R1333 및 R1335)가 PAM 인식에 중요하다는 것을 알았기 때문에, 본 발명자들은 스타필로코쿠스 아우레우스 Cas9 (SaCas9)의 PAM-상호작용 도메인 (PI 도메인)에서 상동성 잔기를 찾기 위해 Cas9 이종상동유전자의 정렬을 생성하였다 (도 6 참고). 본 발명자들 등은 이전에 SaCas9의 PAM이 NNGRRT (서열식별번호:46) (여기서, N은 임의의 뉴클레오티드이고, R은 A 또는 G임)임을 제시한 바 있다. 본 발명자들의 데이터를 기준으로 PAM의 제3 위치에서 G에 대한 선호도가 가장 엄격한 요건인 것으로 여겨졌으며, 본 발명자들은 양으로 하전된 잔기, 예컨대 리신 (K) 또는 아르기닌 (R)이 상기 상호작용을 매개할 수 있다고 가정하였다. 도 6에 제시된 바와 같이, SpCas9의 R1333 및 R1335에 대한 상동성 영역에서 SaCas9의 수많은 후보 잔기, 예컨대 K1101, R1012, R1015, K1018 및 K1023가 있다.
돌연변이체 클론이 표준적인 NNGRRT PAM (서열식별번호:46)을 함유하는 부위를 여전히 분할할 수 있는지, 또는 가능하게는 이전에는 표적화될 수 없었던 NNARRT의 PAM (서열식별번호:43)을 분할할 수 있는지를 결정하기 위해, 본 발명자들은 이들 5가지 위치에서의 알라닌 (A) 및 글루타민 (Q) 치환을 생성하였다 (도 7). 본 발명자들은 본 발명자들의 박테리아 검정 (이전의 특허 출원에 기재되었음)을 이용하였으며, 여기서 Cas9의 활성은 선택적 조건 하에 플레이팅할 때 박테리아 콜로니의 생존에 의해 가시화될 수 있다. Cas9의 상대적 활성은 비-선택적 배지에 비해 선택적 배지 상에서 성장한 박테리아 콜로니의 비를 계산함으로써 정량화할 수 있었다. 도 7에서, 본 발명자들은 R1015A 및 R1015Q 돌연변이만이 표준적인 NNGAGT (서열식별번호:5) PAM을 인식하는 SaCas9의 능력에 영향을 미치는 반면에, 어떠한 돌연변이도 NNARRT (서열식별번호:43) PAM (NNAAGT (서열식별번호:41) 또는 NNAGGT (서열식별번호:42))의 표적화를 가능하게 하지 않았음을 제시하였다. 이들 결과는 R1015가 SaCas9에 의한 PAM 인식에서 소정의 역할을 한다는 것을 시사한다.
이어서, 본 발명자들은 무작위로 돌연변이된 야생형 SaCas9 또는 R1015Q 변이체를 선택하고, NNAAGT (서열식별번호:41) 또는 NNAGGT (서열식별번호:42) PAM을 함유하는 부위에 대한 변경된 PAM 특이성 클론을 선택하였다 (SpCas9에 대해 이전에 기재된 바와 같음). 본 발명자들은 이들 PAM을 표적화할 수 있는 수많은 돌연변이체 클론을 확인하고, 재스크리닝하고, 시퀀싱하였으며, 이들의 아미노산 서열을 도 8 (및 표 6)에 제시하였다. 이들 서열을 요약하면, 수많은 변화가 SaCas9 특이성을 변경시키는데 매우 중요한 것으로 여겨졌지만 (R1015Q, R1015H, E782K), 다른 많은 돌연변이 또한 기여할 수 있다 (N968K, E735K, K929R, A1021T, K1044N).
NNARRT (서열식별번호:43)에 대한 SaCas9의 PAM 특이성을 변경시키는데 필수적인 위치 및 돌연변이를 확인한 후, 본 발명자들은 단일, 이중 및 삼중 돌연변이체 조합을 만들어서 특이성 변화에 대해 가장 풍부한 돌연변이의 기여를 평가하였다 (표 5). 본 발명자들의 양성 선택 (이전에 기재됨)에서 다양한 PAM에 대해 이들 돌연변이를 시험하였을 때, 본 발명자들은 수많은 돌연변이가 표준적인 NNGAGT (서열식별번호:5) 및 비-표준적인 NNAAGT (서열식별번호:41) 또는 NNAGGT (서열식별번호:42) PAM 둘 다에 대한 활성을 허용하는 반면에, 야생형 SaCas9 효소는 비-표준적인 PAM에 대해 매우 낮은 활성을 가졌다는 것을 관찰하였다. 구체적으로, 삼중 돌연변이가 PAM의 제3 위치에서 완화된 특이성을 가능하게 하여 (KKQ, KKH, GKQ, GKH - 위치 E782/N968/R1015에 대한 돌연변이를 기준으로 명명함), 표준적인 NNGRRT (서열식별번호:46)에 대한 NNRRRT (서열식별번호:45)의 컨센서스 PAM 모티프를 유도하는 것처럼 여겨졌다. PAM 요건의 이러한 완화는 이론적으로 SpCas9의 표적화 범위를 배가시킨다. 이후, 변이체는 위치 782, 968 및 1015에 대한 그들의 신원을 기준으로 명명될 것이다. 예를 들어, E782K/N968K/R1015H는 SaCas9 KKH 변이체로 명명될 것이다.
Figure pct00027
다음으로, 본 발명자들은 조작된 변이체가 인간 세포 상태에서 비-표준적인 PAM을 표적화할 수 있는지 여부를 결정하기 위해, 인간 세포 EGFP 파괴 검정 (이전에 기재됨)에서 삼중 돌연변이체 중 2가지를 평가하였다 (도 9). 비-표준적인 PAM을 함유하는 EGFP 유전자 내의 부위를 표적화할 수 있는 변이체는 EGFP 코딩 프레임을 파괴하여, 신호의 소실을 유도할 것이다. 그 결과, KKQ 및 KKH 돌연변이체 둘 다 표준적인 NNGRRT (서열식별번호:46) PAM에 대하여 야생형 SaCas9와 유사한 활성을 보유하는 반면에, NNARRT (서열식별번호:43) PAM에 대해서는 훨씬 더 높은 활성을 가진 것으로 드러났다.
전반적으로, 본 발명자들은 PAM의 제3 위치에서 G에서 R (A 또는 G)로 야생형 효소의 선호도를 완화시키는 것으로 여겨지는 SaCas9에서의 돌연변이 (KKQ 또는 KKH 변이체)를 확인한 바 있다. 이는 SaCas9의 표적화를 NNGRRT (서열식별번호:46) PAM 제한에서 NNRRRT (서열식별번호:45) PAM으로 효율적으로 완화시킨다.
본 발명자들은 인간 세포에서 NNARRT (서열식별번호:43) PAM을 표적화할 수 있는 변이체를 성공적으로 유도하였기 때문에, 다음으로 본 발명자들은 본 발명자들이 NNCRRT (서열식별번호:47) 또는 NNTRRT (서열식별번호:48)에 대해 특이성을 갖는 변이체를 조작할 수 있는지 여부에 대해 의문을 가졌다. 이를 위해, 본 발명자들은 먼저 R1015를 E로 (PAM의 제3 위치에서 C에 대해 특이성을 갖는 경우) 및 L 또는 M으로 (PAM의 제3 위치에서 T에 대해 특이성을 갖는 경우) 돌연변이시키고, 본 발명자들의 박테리아 양성 선택 검정에서 (이전에 기재됨) 그들의 예상된 PAM에 대해 이들을 시험하였다 (도 10). 본 발명자들은 야생형 SaCas9가 NNCAGT (서열식별번호:511) PAM을 함유하는 부위를 비효율적으로 분할할 수 있고, R1015E 변이체가 동일한 부위에 대해 약간 더 활성을 가지며, 야생형 또는 임의의 다른 지정된 돌연변이는 다른 PAM에 대해 활성을 전달하지 않는 것으로 관찰하였다 (도 10). R1015Q에서 본 발명자들이 확인한 바와 같이, 이는 NNCRRT (서열식별번호:47) 및 NNTRRT (서열식별번호:48) PAM을 표적화할 수 있는 SaCas9 변이체를 조작하기 위해 다른 돌연변이가 필요할 것임을 시사하였다.
NNARRT (서열식별번호:43) PAM에 대한 SaCas9 진화된 변이체의 경우, R1015(H/Q)와 함께 E782K 및 N968K 돌연변이가 필요하며 필수적이었다. 이들 돌연변이가 이들의 예상된 PAM에 대한 R1015(E/L/M) 변이체의 활성을 증가시키는지 여부를 시험하기 위해, 본 발명자들은 KKE, KKL 및 KKM 변이체를 생성하였다. 도 11에 제시된 바와 같이, KKE, KKL 및 KKM 모두 그들의 예상된 PAM에 대해 강력한 활성을 가졌다.
또한, 본 발명자들은 KKQ, KKH, KKE, KKL 또는 KKM 변이체가 PAM의 제3 위치에 있는 임의의 뉴클레오티드에 대해 완화된 특이성을 갖는지 여부에 대해 의문을 가졌고, 이에 본 발명자들은 NNNRRT PAM을 함유하는 본 발명자들의 박테리아 양성 선택 검정에서 수많은 부위를 조사하였다. 도 11에 제시된 바와 같이, 몇몇 예외는 있지만 거의 모든 이들 변이체는 NNNRRT PAM을 함유하는 시험된 모든 부위를 분할할 수 있다. 이는 이들이 NNNRRT 부위를 효율적으로 표적화할 수 있기 때문에, PAM의 제3 위치에서 완화된 특이성을 가졌음을 나타내었다. 이는 몇몇 NNNRRT 부위에 대해서는 매우 낮은 활성을 가지면서 NNGAGT (서열식별번호:5) 부위만을 효율적으로 표적화할 수 있는 야생형 단백질 (ENR)과는 대조적이다. 요약하면, KKH (및 도 11에 제시된 다른 유사한 유도체) 변이체는 박테리아에서 NNNRRT PAM을 함유하는 부위를 표적화할 수 있고, 이는 SaCas9의 표적화 범위를 효율적으로 4배화시킨다.
따라서, KKH 변이체 (및 도 6에 도시된 일부 다른 변이체)는 박테리아에서 NNNRRT PAM을 표적화할 수 있고, 이는 SaCas9의 표적화 범위를 효율적으로 4배화시킨다.
Figure pct00028
Figure pct00029
Figure pct00030
Figure pct00031
Figure pct00032
Figure pct00033
Figure pct00034
Figure pct00035
실시예 3에 대한 방법
하기 물질 및 방법을 실시예 3에서 사용하였다.
플라스미드 및 올리고뉴클레오티드
올리고뉴클레오티드를 표 11에 열거하고, sgRNA 표적 부위를 표 12에 열거하고, 이 연구에 사용된 플라스미드를 표 10에 열거하였다.
박테리아 Cas9/sgRNA 발현 플라스미드를 이용하여, 각각 별도의 T7 프로모터 하에 발현되는 SaCas9 및 sgRNA의 인간 코돈 최적화된 버전 둘 다를 발현시켰다. 이 선택에서 사용된 박테리아 발현 플라스미드는 BPK2101로부터 유도한 반면에 (실시예 1-2 참고), 부위-고갈 검정에 사용된 것은 짧아진 반복부:항-반복부 서열을 갖는 sgRNA를 발현하도록 변형시켰다 (하기 참고). 이들 박테리아 발현 플라스미드에서 모든 sgRNA는 T7 프로모터로부터의 적절한 발현을 위해 스페이서 서열의 5' 말단에서 2개의 구아닌을 포함하였다.
SaCas9 변이체의 라이브러리를 생성하기 위해, SaCas9의 아미노산 M657-G1053을 뮤타짐 II (애질런트 테크놀로지즈)를 이용하여 ~5.5 돌연변이/킬로베이스의 빈도로 무작위로 돌연변이시켰다. 야생형 및 R1015Q SaCas9 둘 다 돌연변이 유발을 위한 출발 주형으로 사용하여, 6x106 초과 클론의 추정된 복잡도를 갖는 2가지 라이브러리를 생성하였다.
표적 부위를 코딩하는 올리고뉴클레오티드 듀플렉스를 XbaI/SphI-소화된 p11-lacY-wtx1로 라이게이션시킴으로써 양성 선택 플라스미드를 조립하였다 (Chen, Z. & Zhao, H. A highly sensitive selection method for directed evolution of homing endonucleases. Nucleic Acids Res 33, e154 (2005)). 부위-고갈 실험의 경우, 상이한 스페이서 서열을 함유하는 2가지 별도의 라이브러리를 생성하였다. 각각의 라이브러리의 경우, (PAM 대신에) 스페이서 서열에 인접한 8개의 무작위화된 뉴클레오티드를 함유하는 올리고뉴클레오티드를 하부 가닥 프라이머와 복합체화시키고, Klenow(-exo)를 이용하여 채웠다 (표 11 참고). 생성된 생성물을 EcoRI에 의해 소화시키고, EcoRI/SphI-소화된 p11-lacY-wtx1로 라이게이션시켰다. 두 부위-고갈 라이브러리의 추정된 복잡도는 4x106 초과의 클론이었다.
인간 세포 실험의 경우, 인간 코돈-최적화된 야생형 및 변이체 SaCas9를 CAG 프로모터를 함유하는 플라스미드로부터 발현시켰다 (표 12). sgRNA 발현 플라스미드 (U6 프로모터를 함유함)는 스페이서 서열을 코딩하는 올리고뉴클레오티드 듀플렉스를 BsmBI 소화된 VVT1에 라이게이션시킴으로써 생성하였다 (실시예 1-2 참고, 또는 BPK2660 (각각 전장 120 nt crRNA:tracrRNA sgRNA 또는 84 nt 짧아진 반복부:항-반복부 버전을 함유함). 인간 발현을 위해 이 연구에서 사용된 모든 sgRNA는 U6 프로모터로부터의 적절한 발현을 보장하기 위해 스페이서의 5' 말단에 1개의 구아닌을 포함하였고, 또한 이전에 기재된 것과 유사한 짧아진 sgRNA를 사용하였다 (도 37A-B) (Ran, F.A. et al. In vivo genome editing using Staphylococcus aureus Cas9. Nature 520, 186-191 (2015)).
Cas9 이종상동유전자 서열의 생물정보 분석
이전의 연구에서 수행한 것과 유사하게 (Fonfara, I. et al. Phylogeny of Cas9 determines functional exchangeability of dual-RNA and Cas9 among orthologous type II CRISPR-Cas systems. Nucleic Acids Res 42, 2577-2590 (2014); Ran, F.A. et al. In vivo genome editing using Staphylococcus aureus Cas9. Nature 520, 186-191 (2015); Anders, C., Niewoehner, O., Duerst, A. & Jinek, M. Structural basis of PAM-dependent target DNA recognition by the Cas9 endonuclease. Nature 513, 569-573 (2014)), SpCas9 및 SaCas9 둘 다와 유사한 Cas9 이종상동유전자를 ClustalW2 (ebi.ac.uk/Tools/msa/clustalw2/)를 이용하여 정렬하였다. 생성된 계통수 및 단백질 정렬을 지니어스 버전(Geneious version) 8.1.6 및 ESPript (espript.ibcp.fr/ESPript/ESPript/)를 이용하여 가시화하였다.
박테리아-기재 양성 선택 검정
박테리아 양성 선택 검정을 이전에 기재된 것과 같이 수행하였다 (실시예 1-2 참고). 간략히, Cas9/sgRNA 플라스미드를 양성 선택 플라스미드를 함유하는 이. 콜라이 BW25141(λDE3) (Kleinstiver et al., Nucleic Acids Res 38, 2411-2427 (2010))에 형질전환시켰다. 형질전환체를 비-선택적 (클로람페니콜) 및 선택적 (클로람페니콜 + 10 mM 아라비노스) 조건 둘 다에 플레이팅하였다. 선택 플라스미드의 Cas9 분할은 퍼센트 생존: (선택적 플레이트 상의 콜로니의 #/비-선택적 플레이트 상의 콜로니의 #)x100을 계산함으로써 추정하였다. 대안적인 PAM을 인식할 수 있는 SaCas9 변이체를 선택하기 위해, 돌연변이된 PI 도메인을 갖는 야생형 및 R1015Q 라이브러리를, NNAAGT (서열식별번호:41), NNAGGT (서열식별번호:42), NNCAGT (서열식별번호:511), NNCGGT (서열식별번호:512), NNTAGT (서열식별번호:513), 또는 NNTGGT (서열식별번호:514) PAM을 갖는 양성 선택 플라스미드를 함유하는 적격 이. 콜라이 BW25141(λDE3)에 형질전환시켰다. 대략 1x105 클론을 선택적 조건에 대해 플레이팅함으로써 스크리닝하고, 선택 플라스미드를 분할할 것으로 추정되는 SaCas9 변이체를 함유하는 생존 콜로니를 미니프렙 (MGH DNA Core)에 의해 단리하였다. 모든 변이체를 양성 선택 검정에서 개별적으로 재스크리닝하고, ~20% 초과의 생존을 갖는 것들을 시퀀싱하여, 대안적인 PAM의 인식에 필요한 돌연변이를 결정하였다.
박테리아-기재 부위-고갈 검정
부위-고갈 실험을 이전에 기재된 바와 같이 수행하였다 (실시예 1-2 참고). 간략히, 무작위화된 PAM 라이브러리를 야생형, 촉매 불활성 (D10A/H557A), 또는 KKH 변이체 SaCas9/sgRNA 플라스미드를 함유하는 적격 이. 콜라이 BW25141(λDE3)에 전기천공하였다. 1x105 초과의 콜로니를 클로람페니콜/카르베니실린 플레이트 상에 플레이팅하고, 생존 콜로니 내에 함유된 Cas9 표적화에 내성인 PAM을 갖는 선택 플라스미드를 맥시프렙 (퀴아젠)에 의해 단리하였다. 스페이서 서열 및 PAM을 함유하는 플라스미드의 영역을 표 11에 열거된 프라이머를 사용하여 PCR에 의해 증폭시켰다. 다나-파버 캔서 인스티튜트 몰레큘라 바이올로지 코어에서 일루미나 MiSeq 고산출량 시퀀싱을 작동시키기 전에, KAPA HTP 라이브러리 제조 키트 (카파 바이오시스템즈)를 이용하여, 각각의 부위-고갈 조건으부터의 ~500 ng 정제된 PCR 생성물을 사용하여 듀얼-인덱스드 Tru-Seq 일루미나 시퀀싱 라이브러리를 생성하였다. 스크립트를 변형시켜 8개의 무작위화된 뉴클레오티드를 분석한 것을 제외하고는, 부위-고갈 실험으로부터의 데이터를 이전에 기재된 바와 같이 분석하였다 (실시예 1-2 참고). PAM을 인식하는 Cas9의 능력은 임의의 주어진 PAM의 선택후 PAM 고갈 값 (PPDV)을 계산함으로써 결정하였다: 해당 PAM의 선택후 빈도 대 선택전 라이브러리 빈도의 비. 촉매 불활성 SaCas9를 사용하는 대조군 실험을 이용하여, 0.794의 PPDV가 투입 라이브러리에 대한 통계적으로 유의한 고갈을 나타냄을 수립하였다.
인간 세포 배양 및 형질감염
U2OS 세포를 본 발명자들의 콜라보레이터 티. 캐쏘멘(collaborator T. Cathomen, 프라이부르크)으로부터 입수하였고, EGFP-PEST 리포터 유전자의 단일 통합 카피를 보유한 U2OS.EGFP 세포 (Reyon, D. et al. FLASH assembly of TALENs for high-throughput genome editing. Nat Biotechnol 30, 460-465 (2012))를 10% FBS, 페니실린/스트렙토마이신 및 2 mM GlutaMAX (라이프 테크놀로지즈)를 함유하는 어드밴스드 DMEM 배지 (라이프 테크놀로지즈)에서 37℃에서 5% CO2 하에 배양시켰다. 세포주 신원은 STR 프로파일링 (ATCC) 및 심층-시퀀싱에 의해 확인하였고, 세포를 마이코플라즈마 오염에 대해 격주로 시험하였다. U2OS.EGFP 배양 배지에 400 μg/mL G418을 추가로 보충하였다. 제조자의 지시에 따라 론자 4D-뉴클레오펙터의 DN-100 프로그램을 이용하여 세포를 750 ng Cas9 플라스미드 및 250 ng sgRNA 플라스미드로 공동-형질감염시켰다.
인간 세포 EGFP 파괴 검정
EGFP 파괴 실험을 이전에 기재된 바와 같이 수행하였다 (Fu, Y. et al. High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells. Nat Biotechnol 31, 822-826 (2013); Reyon, D. et al. FLASH assembly of TALENs for high-throughput genome editing. Nat Biotechnol 30, 460-465 (2012)). 대략 52 시간 동안 형질감염시킨 후, 포르테싸 유세포 분석기 (비디 바이오사이언시즈)를 이용하여 형질감염된 U2OS.EGFP 세포에서 EGFP 형광을 측정하였다. Cas9 및 빈 U6 프로모터 플라스미드의 음성 대조군 형질감염을 이용하여 모든 실험에 대해 ~2.5% 백그라운드 EGFP 손실을 수립하였다 (도면에서 적색 점선으로 표시됨).
T7E1 검정
T7E1 검정을 이전에 기재된 바와 같이 수행하여 (Reyon, D. et al. FLASH assembly of TALENs for high-throughput genome editing. Nat Biotechnol 30, 460-465 (2012)), 인간 세포의 내인성 좌위에서 Cas9-유도된 돌연변이 유발을 정량화하였다. 대략 72 시간 동안 형질감염시킨 후, 아젠코트 디엔어드밴스 게놈 DNA 단리 키트 (베크만 코울터 게노믹스)를 이용하여 게놈 DNA를 단리하였다. 표 11에 열거된 프라이머를 이용하여 ~100 ng의 게놈 DNA로부터 표적 좌위를 PCR에 의해 증폭시켰다. 아젠코트 앰퓨어 XP 클린업 스텝 (베크만 코울터 게노믹스) 이후, T7E1 (뉴 잉글랜드 바이오랩스)에 의해 소화시키기 전에 ~200 ng의 정제된 PCR 생성물을 변성시키고 혼성화시켰다. 제2 클린업 스텝 이후, 퀴악셀 모세관 전기영동 장비 (퀴아젠)를 이용하여 돌연변이 유발 빈도를 정량화하였다.
GUIDE- seq 실험
GUIDE-seq 실험을 이전에 기재된 바와 같이 수행하여 분석하였다 (Tsai, S.Q. et al. GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases. Nat Biotechnol 33, 187-197 (2015)). 간략히, U2OS 세포를 상기 기재된 바와 같이 Cas9 및 sgRNA 플라스미드, 뿐만 아니라 매입된 NdeI 부위를 갖는 포스포릴화된 포스포로티오에이트-변형된 이중-가닥 올리고데옥시뉴클레오티드 (dsODN) 100 pmol로 형질감염시켰다. 제한 단편 길이 다형 (RFLP) 분석을 수행하여, dsODN-태그 통합 빈도를 결정하였고 (실시예 1-2 참고; Tsai, S.Q. et al. GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases. Nat Biotechnol 33, 187-197 (2015)), T7E1 검정을 수행하여 온-타겟 Cas9 돌연변이 유발 빈도를 정량화하였다. dsODN 태그-특이적 증폭 및 라이브러리 제조 (Tsai, S.Q. et al. GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases. Nat Biotechnol 33, 187-197 (2015))를 일루미나 MiSeq 시퀀서를 이용한 고산출량 시퀀싱 이전에 수행하였다. 잠재적인 오프-타겟 부위를 맵핑하였을 때, 온-타겟 스페이서 서열에 대한 정렬의 컷오프는 21개 뉴클레오티드 스페이서의 경우 8개 미스매치, 22개 뉴클레오티드 스페이서의 경우 9개 미스매치, 및 23개 뉴클레오티드 스페이서의 경우 10개 미스매치로 설정하였다. 잠재적인 DNA- 또는 RNA-벌지를 갖는 오프-타겟 부위 (Lin, Y. et al. CRISPR/Cas9 systems have off-target activity with insertions or deletions between target DNA and guide RNA sequences. Nucleic Acids Res 42, 7473-7485 (2014))를 수동 정렬에 의해 확인하였다.
표 10 - 실시예 3에서 사용된 플라스미드
Figure pct00036
표 11 - 실시예 3에서 사용된 올리고뉴클레오티드
Figure pct00037
표 12 - 실시예 3에 대한 sgRNA 표적 부위
Figure pct00038
Figure pct00039
Figure pct00040
*도 1c 및 1e, 도 32에서 사용됨
**도 3, 도 36A-B에서 GUIDE-seq 실험을 위해 사용됨
실시예 3. 스타필로코쿠스 아우레우스 Cas9의 PAM 특이성의 조작
CRISPR-Cas9 뉴클레아제에 의한 부위-특이적 DNA 분할은 일차적으로 RNA-DNA 상호작용에 의해 지시되지만, 프로토스페이서 인접 모티프 (PAM)의 Cas9-매개된 인식 또한 필요로 한다. 흔히 사용되는 스트렙토코쿠스 피오게네스 Cas9가 그의 NGG PAM 내의 2개의 뉴클레오티드만에 대해서만 특이성을 갖지만, 목적하는 특성을 갖는 다른 Cas9 이종상동유전자는 더 긴 PAM을 인식한다. 특이성의 관점으로부터 잠재적인 이점이 있지만, 연장된 PAM 서열은 게놈 편집 적용을 위한 Cas9 이종상동유전자의 표적화 범위를 제한할 수 있다. 이러한 Cas9 이종상동유전자에 의해 표적화가능한 서열의 범위를 넓히는 한 가능한 전략은, PAM 내의 특정 위치에 대한 완화된 특이성을 갖는 변이체를 진화시키는 것일 수 있다. 여기서, 본 발명자들은 바이러스 전달을 요하는 적용에 유용한 소형 이종상동유전자인 스타필로코쿠스 아우레우스 Cas9 (SaCas9)의 NNGRRT (서열식별번호:46) PAM 특이성을 변경시키기 위해 분자 진화를 이용하였다. KKH SaCas9로 지칭되는 본 발명자들이 확인한 한 변이체는 NNNRRT PAM을 갖는 내인성 인간 표적 부위에서 강력한 게놈 편집 활성을 제시하였다. 중요하게는, GUIDE-seq 방법을 이용하여, 본 발명자들은 야생형 및 KKH SaCas9 둘 다 인간 세포에서 필적할만한 수의 오프-타겟 효과를 유도한다는 것을 제시하였다. KKH SaCas9는 SaCas9의 표적화 범위를 거의 2배 내지 4배 증가시켰고, 이는 야생형 뉴클레아제에 의해서는 변경될 수 없는 서열의 표적화를 가능하게 한다. 더욱 일반적으로, 이들 결과는 Cas9 이종상동유전자의 표적화 범위를 넓히기 위한 PAM 특이성 완화의 실현가능성을 입증한다. 본 발명자들의 분자 진화 전략은 PAM과 접촉하는 특이적 잔기에 대한 구조적 정보 또는 선험적 지식을 필요로 하지 않으며, 따라서 광범위한 Cas9 이종상동유전자에 적용가능해야 한다.
결과
본 발명자들은 구조적 정보를 필요로 하지 않는 완화된 PAM 인식 특이성을 갖는 Cas9 변이체를 조작하기 위한 비편파적인 유전적 접근법을 고안하였다. 본 발명자들은 본 발명자들이 이들 연구를 시작할 시점에는 구조적 데이터가 입수가능하지 않았던 SaCas9를 이용하여 이 전략을 시험하였다. 초기 단계에서, 본 발명자들은 구조적으로 잘 특성분석된 SpCas9와의 서열 비교에 의해 SaCas9에 대한 PAM-상호작용 도메인을 조심스럽게 추정하고자 하였다 (Jiang et al., Science 348, 1477-1481 (2015); Anders et al., Nature 513, 569-573 (2014); Jinek et al., Science (2014); Nishimasu et al., Cell (2014)). SpCas9 및 SaCas9가 일차 서열 수준에서 실질적으로 상이하였지만 (도 21a, 도 29), 10개 추가의 이종상동유전자를 이용한 둘 다의 정렬은 SaCas9에 대해 예상된 PAM-상호작용 도메인을 조심스럽게 규정하는 것을 가능하게 하였다 (실시예 3에 대한 방법; 도 29 및 30 참고).
SaCas9 PAM의 제3 위치에 있는 구아닌이 가장 엄격한 특이성을 갖는 염기이기 때문에 (Ran et al., Nature 520, 186-191 (2015)), 본 발명자들은 예상된 PI 도메인을 무작위로 돌연변이시키고, 이전에 기재된 본 발명자들의 박테리아 세포-기재 방법을 이용하여 (실시예 1-2 참고) 제3 PAM 위치에서 다른 가능한 3개의 뉴클레오티드 (즉, NN[A/C/T]RRT PAM (NNHRRT (서열식별번호:44)); 도 31a) 각각을 갖는 부위를 분할할 수 있는 돌연변이체를 선택하기 위해 시도하였다. NNARRT (서열식별번호:43) 및 NNCRRT (서열식별번호:47) PAM을 함유하는 부위에 대한 선택으로부터 생존 변이체 모두가 아니라 하나가 R1015H 돌연변이를 보유한 반면에, 본 발명자들은 NNTRRT (서열식별번호:48) PAM에 대한 선택으로부터는 어떠한 변이체도 수득하지 않았다. 이들 결과는, R1015가 SpCas9 PAM의 제3 위치에 있는 구아닌의 인식에 참여할 수 있음을 강력하게 시사한다. 실제로, 본 발명자들의 정렬에서, 본 발명자들은 이전에 PAM의 제3 염기 위치의 인식과 연관된 잔기인 SpCas9 R1335 (도 30) 부근에 SaCas9의 R1015가 있음을 확인하였다 (실시예 1-2 참고; Anders, C., Niewoehner, O., Duerst, A. & Jinek, M. Structural basis of PAM-dependent target DNA recognition by the Cas9 endonuclease. Nature 513, 569-573 (2014)). 이와 일치하게, 본 발명자들은 본 발명자들의 박테리아 선택 시스템에서 시험하였을 때 (도 31b), R1015의 알라닌 또는 글루타민으로의 돌연변이가 NNGRRT (서열식별번호:46) PAM을 함유하는 표적 부위에 대한 SaCas9 활성을 실질적으로 감소시킨 것을 확인하였다 (도 21b). R1015 부근에 있는 다른 양으로 하전된 잔기의 알라닌 또는 글루타민 치환은 SaCas9 활성에 대해 강력한 효과를 갖지 않았다 (도 21b, 도 30).
본 발명자들의 박테리아-기재 선택 결과는 또한 R1015H 돌연변이가 PAM의 제3 위치에서 SaCas9의 특이성을 적어도 부분적으로 완화시킬 수 있음을 시사한다. 그러나, 본 발명자들은 NNNRRT PAM의 제3 위치에 임의의 뉴클레오티드를 갖는 부위에 대해 시험하였을 때 (도 21c) R1015H 단일 돌연변이체가 이전에 기재된 본 발명자들의 인간 세포-기재 EGFP 파괴 검정에서 최적보다 낮은 활성을 가졌음을 확인하였다 (Fu et al., Nat Biotechnol 31, 822-826 (2013); Reyon et al., Nat Biotechnol 30, 460-465 (2012)). 이는 추가의 돌연변이가 인간 세포에서 R1015H 돌연변이체의 활성을 증가 또는 최적화시키는데 필요할 수 있음을 시사하기 때문에, 본 발명자들은 R1015Q 돌연변이 또한 보유한 SaCas9의 예상된 PI 도메인을 포함하는 영역을 무작위로 돌연변이시켰다. 이어서, 본 발명자들은 본 발명자들의 박테리아 선택 시스템을 이용하여 이 라이브러리로부터 3가지 상이한 NNHRRT (서열식별번호:44) PAM 각각을 갖는 표적 부위를 분할할 수 있는 변이체를 선택하였다. R1015H와는 달리 R1015Q가 돌연변이체는 박테리에서 활성을 제시하지 않기 때문에 본 발명자들은 이를 사용하였다 (도 21b). NNTRRT (서열식별번호:48) PAM에 대한 선택시 생존 클론이 다시 관찰되지는 않았지만, NNARRT (서열식별번호:43) 또는 NNCRRT (서열식별번호:47)에 대한 R1015Q 변이체를 갖는 선택은 E782, K929, N968에서 돌연변이를 생성하였고, 놀랍게도 1015의 Q를 H로 돌연변이시켰다.
야생형 SaCas9로부터의 선택 결과와 조합하여, 모든 선택에 걸쳐 확인된 가장 빈번한 미스센스 돌연변이는 E782K, K929R, N968K 및 R1015H이었고 (도 21d), 이는 이들 돌연변이의 조합이 SaCas9 PAM의 제3 위치에 A 또는 C를 함유하는 부위의 효율적인 분할을 허용할 수 있음을 시사한다. 따라서, 본 발명자들은 PAM의 제3 위치에서 (즉, NNNRRT PAM 상에) 4가지 염기를 각각 보유하는 부위로 표적화된 sgRNA를 사용하여 인간 세포-기재 EGFP 파괴 검정을 이용하여 이들 돌연변이의 상이한 조합을 함유하는 SaCas9 변이체에 대해 시험하였다 (도 21e, 도 32). 본 발명자들은 삼중 돌연변이체 조합 E782K/N968K/R1015H 및 E782K/K929R/R1015H를 갖는 변이체는 NNNRRT PAM을 갖는 부위에서 매우 활성인 반면에 (도 21e, 도 32), 4개의 모든 돌연변이 (E782K/K929R/N968K/R1015H)를 함유하는 사중 돌연변이체 변이체는 이들 부위에 대해 전반적으로 더 낮은 활성을 가짐을 확인하였다 (도 32). 본 발명자들은 추가의 특성분석을 위해 E782K/N968K/R1015H (이후 KKH 변이체로 지칭됨)를 선택하였고, 본 발명자들의 인간 세포-기재 EGFP 파괴 검정을 이용하여 KKH 변이체를 포함하는 3가지 모든 치환이 활성에 필요함을 입증하였다 (도 21e).
KKH 및 야생형 SaCas9의 PAM 특이성을 더욱 포괄적으로 정의하기 위해, 본 발명자들은 이전에 기재한 본 발명자들의 박테리아 세포-기재 부위-고갈 검정을 이용하였다 (실시예 1-2 참고) (도 33). 이 방법은 무작위화된 PAM 서열을 보유한 DNA 플라스미드의 상대적인 분할 (및 그에 따라 박테리아 세포에서의 고갈)을 확인함으로써 Cas9 PAM 특이성 프로파일을 생성하였고, 선택후 PAM 고갈 값 (PPDV)으로 정량화하였다. 본 발명자들은 PAM 대신에 8개의 무작위화된 염기를 갖는 각각의 2가지 상이한 스페이서 서열을 갖는 라이브러리를 이용하여 야생형 및 KKH SaCas9 둘 다에서 부위-고갈 실험을 수행하였다 (도 33). 촉매 불활성 SaCas9를 이용하는 대조군 실험은 임의의 PAM 서열이 적게 고갈되었음을 제시하였고 (도 34a), 이는 0.794의 PPDV로서 통계적으로 유의한 고갈에 대한 역가를 수립하는 것을 가능하게 하였다 (도 34b). 이전의 실험은, 본 발명자들의 박테리아 부위-고갈 검정에서 PPDV가 <0.2인 PAM이 본 발명자들의 인간 세포-기재 EGFP 파괴 검정에서 효율적으로 분할될 수 있음을 제시한 바 있다 (실시예 1-2 참고). 야생형 SaCas9의 경우, 가장 많이 고갈된 PAM (두 라이브러리로부터 수득된 평균 PPDV를 기준으로)은 예상된 바와 같이 4가지 NNGRRT (서열식별번호:46) PAM이었다 (도 21f 및 도 34c). 흥미롭게도, 평균 PPDV가 <0.1인 다른 PAM은 NNGRRN (서열식별번호:49) 형태를 갖는 것들을 포함하였고 (도 34d), 이는 일부 스페이서 서열의 경우 PAM의 마지막 위치가 본 발명자들의 박테리아-기재 검정에서 T로 완전히 규명될 수 없음을 시사한다 (비록 이전의 보고에서 시험관내 PAM 고갈 검정, ChIP-seq 및 내인성 인간 부위의 표적화에 의해 PAM의 제6 위치에서 티민이 가장 바람직하였음이 입증되었지만 (Ran, F.A. et al. In vivo genome editing using Staphylococcus aureus Cas9. Nature 520, 186-191 (2015))). 대조적으로, KKH 변이체의 경우에는, 평균 PPDV가 <0.2인 PAM은 NNGRRT (서열식별번호:46) PAM을 함유할 뿐만 아니라 4가지 모든 NNARRT (서열식별번호:43), 4가지 모든 NNCRRT (서열식별번호:47), 및 4가지 NNTRRT 중 3가지 (서열식별번호:48) PAM을 함유하였다 (도 21f, 도 34c 및 34e). 이들 결과는, KKH SaCas9가 그의 야생형 대응체에 비해 넓은 PAM 표적화 범위를 가진 것으로 여겨짐을 시사한다.
인간 세포에서 KKH SaCas9 변이체의 강력함을 평가하기 위해, 본 발명자들은 다양한 NNNRRT PAM을 함유하는 55가지 상이한 내인성 유전자 표적 부위에 대한 그의 활성을 시험하였다 (도 22a). KKH 변이체는 모든 부위에 걸쳐 24.7%의 평균 돌연변이 유발 빈도로 효율적인 활성을 제시하였고, 상기 부위의 80% (55개 부위 중 44개)는 5% 초과의 파괴를 제시하였다. 55가지 모든 부위에 걸친 KKH SaCas9 활성의 분석은 PAM의 제3 위치에 대한 선호도 순서 (NN[G>A=C>T]RRT; 도 22b) 뿐만 아니라 PAM의 제4/제5 위치에 대한 선호도 순서 (NNN[AG>GG>GA>AA]T; 도 22c)를 나타내었다. 이와 일치하게, 본 발명자들은 NNNRRT PAM의 제3/제4/제5 위치의 16가지 가능한 조합에서의 차이를 관찰하였다 (도 35a). KKH SaCas9는 21-23개 뉴클레오티드 범위의 스페이서 길이 (도 22d), 가변 GC 함량을 갖는 스페이서 서열 (도 35b), 및 가변 GC 함량을 갖는 PAM (도 35c)에 대해 효율적으로 기능하였다. 저효율, 중간 효율 및 고효율 (각각 0-10%, 10-30%, 및 >30% 평균 돌연변이 유발 빈도)로 분할된 부위로부터 유래된 서열 로고는 NNNRRT PAM의 제4 및 제5 위치 외에도 전체 표적 부위에 걸쳐 적은 서열 선호도를 나타내었고, 아마도 고효율로 분할된 부위 상의 제2 PAM 위치에 있는 구아닌에 대해 약간의 선호도를 나타내었다 (도 35d).
KKH 변이체가 야생형 SaCas9에 의해 표적화될 수 없는 PAM의 변형을 가능하게 함을 입증하기 위해, 본 발명자들은 다양한 NNNRRT PAM을 보유하는 부위에 대해 인간 세포에서 이들 뉴클레아제의 직접 비교를 수행하였다. 본 발명자들의 EGFP 파괴 검정 및 16가지 내인성 인간 유전자 표적을 이용하는 16가지 부위의 평가 (각각 도 22e 및 22f)는, KKH SaCas9가 NNNRRT PAM을 보유하는 표적 부위를 강력하게 변형시킨 반면에, 야생형 SaCas9는 NNGRRT (서열식별번호:46) PAM을 갖는 부위만을 효율적으로 표적화하였음을 제시하였다. NNHRRT (서열식별번호:44) PAM을 갖는 24가지 모든 부위의 경우에는, KKH 변이체가 야생형 SaCas9에 비해 실질적으로 높은 비율로 돌연변이 유발을 유도하였고, NNGRRT (서열식별번호:46) PAM을 갖는 8가지 부위의 경우에는 KKH SaCas9가 야생형에 필적할만하거나 그보다 약간 낮은 수준의 돌연변이 유발을 유도하였다 (도 22e 및 22f). 이들 결과는 종합하면, KKH 변이체가 NNNRRT PAM을 갖는 부위를 분할할 수 있고, 이로써 현재 인간 세포에서 야생형 SaCas9에 의해 효율적으로 변경될 수 없는 NNHRRT (서열식별번호:44) PAM을 갖는 부위의 표적화를 가능하게 함을 입증한다.
SaCas9의 게놈에 걸친 특이성에 대한 KKH 돌연변이의 영향을 평가하기 위해, 본 발명자들은 GUIDE-seq (Genome-wide Unbiased Identification of DSBs Enabled by sequencing) 방법을 이용하여 (Tsai, S.Q. et al. GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases. Nat Biotechnol 33, 187-197 (2015)), 동일한 sgRNA를 갖는 야생형 및 KKH SaCas9의 오프-타겟 프로파일을 직접 비교하였다. NNGRRT (서열식별번호:46) PAM을 함유하는 6가지 내인성 인간 유전자 부위로 표적화된 sgRNA를 이용하여 시험하였을 때, 본 발명자들은 야생형 및 KKH SaCas9가 6가지 모든 부위에 대해 거의 동일한 GUIDE-seq 태그 통합률 및 온-타겟 분할 빈도를 유도하였음을 관찰하였다 (각각 도 36a 및 36b). 또한, 야생형 및 KKH SaCas9는 6가지 sgRNA 각각에 의해 유사한 개수의 오프-타겟 부위 돌연변이를 유도하였다 (도 23a 및 23b). KKH 변이체의 경우 오프-타겟 부위가 일반적으로 NNNRRT PAM 모티프에 부착하였고, 야생형 SaCas9의 경우 오프-타겟 부위가 NNGRR[T>G] 모티프에 부착하였다 (도 22b). 시험된 6가지 sgRNA 중에서 가장 많은 개수의 오프-타겟 부위를 유도한 sgRNA 중 하나에 대해, 본 발명자들은 야생형 및 KKH SaCas9에 의해 유사한 개수의 오프-타겟 부위를 관찰하였다. 그러나, 그들의 주어진 상이한 PAM 특이성에 의해 예상될 수 있는 바와 같이 오프-타겟 부위는 야생형과 KKH SaCas9 사이에서 단지 일부만 중복되었다 (도 23b 및 23c). 본 발명자들이 NNGRRT (서열식별번호:46) PAM을 갖는 부위를 표적화하기 위해 KKH 변이체의 사용을 지지하지만 (야생형 SaCas9가 이들 부위에 대해 KKH에 비해 더 높은 온-타겟 활성을 제시할 수 있기 때문에), 이들 결과는 KKH SaCas9만이 예상된 PAM을 갖는 오프-타겟 부위를 분할하고, 전반적으로 야생형 SaCas9에서 관찰된 것에 필적할만한 개수의 오프-타겟 부위를 유도함을 시사한다.
KKH SaCas9의 게놈에 걸친 특이성을 추가로 실험하기 위해, 본 발명자들은 NNHRRT (서열식별번호:44) PAM을 함유하는 부위로 표적화된 5가지 추가의 sgRNA를 시험하였다 (도 23d 및 23e). GUIDE-seq에 의해 검출된 오프-타겟 부위는 전반적으로 개수가 적었고 (이전에 공개된 실험에서 야생형 SpCas9 및 SpCas9 변이체에 의해 관찰된 개수에 필적할만함 (실시예 1-2 참고 (Tsai, S.Q. et al. GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases. Nat Biotechnol 33, 187-197 (2015)), 잠재적인 DNA- 및 RNA-벌지 오프-타겟을 나타내었고 (Lin, Y. et al. CRISPR/Cas9 systems have off-target activity with insertions or deletions between target DNA and guide RNA sequences. Nucleic Acids Res 42, 7473-7485 (2014)), 예상된 PAM 서열을 함유하였다. 종합하면, 본 발명자들의 실험은 야생형 및 KKH SaCas9의 게놈에 걸친 특이성이 유사하였고, 전반적으로 GUIDE-seq에 의해 판단되는 바와 같이 인간 세포에서 낮은 개수의 오프-타겟 돌연변이를 제시하였다.
야생형 SaCas9가 NNGRRT (서열식별번호:46) PAM을 표적화하기 위한 가장 최적의 선택이지만, 본 발명자들이 본원에 기재한 KKH SaCas9 변이체는 NNARRT (서열식별번호:43) 및 NNCRRT (서열식별번호:47) PAM을 갖는 부위를 강력하게 표적화할 수 있고, NNTRRT (서열식별번호:48) PAM을 갖는 부위에 대해 합리적인 성공률을 갖는다. 따라서, 본 발명자들은 KKH 변이체가 무작위 DNA 서열에서 SaCas9의 표적화 범위를 거의 2배 내지 4배만큼 증가시키며, 이로써 고도로 정밀한 표적화를 요하는 다양한 상이한 적용에서 SaCas9를 더욱 광범위하게 이용하는 가능성을 개선시킨다고 조심스럽게 추정하였다. GUIDE-seq를 이용하여, 본 발명자들은 NNGRRT (서열식별번호:46) PAM을 함유하는 동일한 부위로 표적화될 때 KKH SaCas9가 야생형 SaCas9와 유사한 개수의 오프-타겟 돌연변이를 유도함을 입증하였다. 또한, NNHRRT (서열식별번호:44) PAM을 보유한 부위로 표적화될 때 KKH SaCas9는 단지 적은 개수의 오프-타겟 돌연변이를 유도하였다. KKH SaCas9가 야생형 SaCas9에 비해 변형된 PAM 서열을 인식하더라도, 프로토스페이서 및 PAM의 전체 조합 길이가 충분히 길어서 (24 내지 26 bp) KKH 변이체가 인간 게놈에 합리적으로 직교된다면 본 발명자들의 발견은 전혀 놀라운 것이 아니다. 또한, PAM 인식의 변형이 그의 표적 부위와의 Cas9/sgRNA 상호작용 에너지를 변경시킴으로써 특이성을 개선시킬 수 있음이 가능하다 (말단절단된 sgRNA의 개선된 특이성에 대해 이전에 제안한 메카니즘 (Fu, Y., Sander, J.D., Reyon, D., Cascio, V.M. & Joung, J.K. Improving CRISPR-Cas nuclease specificity using truncated guide RNAs. Nat Biotechnol 32, 279-284 (2014)) 또는 D1135E SpCas9 돌연변이체 (실시예 1-2 참고)와 유사함).
실시예 4. SpCas9 - VQR 변이체의 활성의 개선
SpCas9-VQR 변이체가 NGAN PAM에 대한 선호도: NGAG>NGAA=NGAT>NGAC를 갖기 때문에, 본 발명자들은 NGAH PAM (여기서, H = A, C, 또는 T)에 대해 개선된 활성을 갖는 유도체 변이체를 선택하고자 하였다. NGAA, NGAT 또는 NGAC PAM을 갖는 표적 부위를 함유하는 세포에 대한 R1335Q 라이브러리 (무작위로 돌연변이된 PI 도메인을 가짐)를 이용한 선택은 변경된 PAM 특이성을 전달하는 돌연변이를 함유한 추가의 클론을 시퀀싱하는 것을 가능하게 하였다. 이들 클론의 서열은 NGAA, NGAT 또는 NGAC PAM에 대한 PAM 특이성을 변경시키는데 중요할 수 있는 추가의 돌연변이를 나타내었다.
이들 선택의 결과를 기준으로, VQR 변이체 및 24가지 다른 유도체 변이체를 박테리아에서 NGAG, NGAA, NGAT 및 NGAC PAM 부위에 대해 시험하였다. 이들 수많은 유도체 변이체는 NGAH PAM 부위에 대해 VQR 변이체에 비해 더 많이 생존하였고, 이들 중 대부분은 G1218R 돌연변이를 함유하였다 (표 7 및 도 24).
Figure pct00041
박테리아 스크린의 결과로부터 이들 추가의 돌연변이 중 일부가 NGAH PAM 부위에 대한 활성을 개선시킨다는 것이 입증되었으므로, 본 발명자들은 EGFP 파괴 검정으로 인간 세포에서 최상의 후보 중 일부를 시험하였다. 본 발명자들은 VRQR, NRQR 및 YRQR 변이체를 비롯한 이들 수많은 변이체가 NGAH 부위를 표적화하는데 있어서 VQR 변이체를 능가한다는 것을 관찰하였다 (표 8 및 도 25). 이들 클론과 VQR 변이체 사이의 주요 차이점은 이들이 G1218R 돌연변이를 포함한다는 것이다.
Figure pct00042
VRQR 변이체가 시험된 것들 중 가장 강력한 것으로 여겨졌기 때문에, 본 발명자들은 인간 세포에서 9가지 상이한 내인성 부위 (NGAA, NGAC, NGAT 및 NGAG PAM 각각에 대한 2가지 부위, 및 NGCG PAM에 대한 1가지 부위)에 대한 그의 활성을 VQR의 활성과 비교하였다. 이 데이터로부터 VRQR 변이체가 인간 세포에서 시험된 모든 부위에서 VQR 변이체를 능가한다는 것이 드러났다 (도 26).
VRQR 변이체가 VQR 변이체에 비해 개선된 활성을 가짐을 입증한 후에, 본 발명자들은 추가의 치환을 부가하는 것이 활성을 추가로 개선시킬 수 있는지 여부를 결정하고자 하였다. 본 발명자들은 선택으로부터 SpCas9의 PAM 상호작용 포켓에 매우 근접하여 있는 추가의 돌연변이를 관찰하였기 때문에, 이들 돌연변이의 하위집합을 VQR 및 VRQR 변이체에 부가하여, 박테리아에서 NGAG, NGAA, NGAT 및 NGAC PAM을 함유하는 부위에 대해 스크리닝하였다 (표 9 및 도 27). 수많은 유도체 변이체가 NGAT 및 NGAC PAM 부위에 대해 더 높은 활성을 갖는 것으로 보였고, 이에 본 발명자들은 인간 세포에서 이들 변이체를 시험하였다. 본 발명자들은 인간 세포 EGFP 파괴 검정에서 VQR 또는 VRQR 백그라운드에 부가된 돌연변이를 함유하는 추가의 변이체를 시험하였다. 이들 실험은 다시, VRQR이 VQR 변이체에 비해 NGAH PAM에 대해 더욱 강력한 활성을 갖고, VRQR 백본에서 추가의 돌연변이가 유익함을 나타내었다.
Figure pct00043
종합하면, 이들 결과는 SpCas9-VQR 변이체에서 추가의 돌연변이를 포함시키는 것이 NGAN PAM을 함유하는 부위, 구체적으로 NGAH PAM을 함유하는 부위에 대한 활성을 개선시킬 수 있음을 시사한다.
참고문헌
Figure pct00044
Figure pct00045
다른 실시양태
본 발명이 상세한 설명에 의해 기재되었지만, 상기 기재는 첨부된 청구항의 범위에 의해 정의되는 본 발명을 예시하는 것이지 그의 범위를 제한하기 위한 의도는 아님을 이해해야 한다. 다른 측면, 이점 및 변형이 하기 청구항의 범위 내에 있다.
SEQUENCE LISTING <110> THE GENERAL HOSPITAL CORPORATION <120> ENGINEERED CRISPR-CAS9 NUCLEASES WITH ALTERED PAM SPECIFICITY <130> 29539-0163WO1 <140> PCT/US2016/020756 <141> 2016-03-03 <150> 62/127,634 <151> 2015-03-03 <150> 62/165,517 <151> 2015-05-22 <150> 62/239,737 <151> 2015-10-09 <150> 62/258,402 <151> 2015-11-20 <160> 1021 <170> PatentIn version 3.5 <210> 1 <211> 1368 <212> PRT <213> Streptococcus pyogenes <400> 1 Met Asp Lys Lys Tyr Ser Ile Gly Leu Asp Ile Gly Thr Asn Ser Val 1 5 10 15 Gly Trp Ala Val Ile Thr Asp Glu Tyr Lys Val Pro Ser Lys Lys Phe 20 25 30 Lys Val Leu Gly Asn Thr Asp Arg His Ser Ile Lys Lys Asn Leu Ile 35 40 45 Gly Ala Leu Leu Phe Asp Ser Gly Glu Thr Ala Glu Ala Thr Arg Leu 50 55 60 Lys Arg Thr Ala Arg Arg Arg Tyr Thr Arg Arg Lys Asn Arg Ile Cys 65 70 75 80 Tyr Leu Gln Glu Ile Phe Ser Asn Glu Met Ala Lys Val Asp Asp Ser 85 90 95 Phe Phe His Arg Leu Glu Glu Ser Phe Leu Val Glu Glu Asp Lys Lys 100 105 110 His Glu Arg His Pro Ile Phe Gly Asn Ile Val Asp Glu Val Ala Tyr 115 120 125 His Glu Lys Tyr Pro Thr Ile Tyr His Leu Arg Lys Lys Leu Val Asp 130 135 140 Ser Thr Asp Lys Ala Asp Leu Arg Leu Ile Tyr Leu Ala Leu Ala His 145 150 155 160 Met Ile Lys Phe Arg Gly His Phe Leu Ile Glu Gly Asp Leu Asn Pro 165 170 175 Asp Asn Ser Asp Val Asp Lys Leu Phe Ile Gln Leu Val Gln Thr Tyr 180 185 190 Asn Gln Leu Phe Glu Glu Asn Pro Ile Asn Ala Ser Gly Val Asp Ala 195 200 205 Lys Ala Ile Leu Ser Ala Arg Leu Ser Lys Ser Arg Arg Leu Glu Asn 210 215 220 Leu Ile Ala Gln Leu Pro Gly Glu Lys Lys Asn Gly Leu Phe Gly Asn 225 230 235 240 Leu Ile Ala Leu Ser Leu Gly Leu Thr Pro Asn Phe Lys Ser Asn Phe 245 250 255 Asp Leu Ala Glu Asp Ala Lys Leu Gln Leu Ser Lys Asp Thr Tyr Asp 260 265 270 Asp Asp Leu Asp Asn Leu Leu Ala Gln Ile Gly Asp Gln Tyr Ala Asp 275 280 285 Leu Phe Leu Ala Ala Lys Asn Leu Ser Asp Ala Ile Leu Leu Ser Asp 290 295 300 Ile Leu Arg Val Asn Thr Glu Ile Thr Lys Ala Pro Leu Ser Ala Ser 305 310 315 320 Met Ile Lys Arg Tyr Asp Glu His His Gln Asp Leu Thr Leu Leu Lys 325 330 335 Ala Leu Val Arg Gln Gln Leu Pro Glu Lys Tyr Lys Glu Ile Phe Phe 340 345 350 Asp Gln Ser Lys Asn Gly Tyr Ala Gly Tyr Ile Asp Gly Gly Ala Ser 355 360 365 Gln Glu Glu Phe Tyr Lys Phe Ile Lys Pro Ile Leu Glu Lys Met Asp 370 375 380 Gly Thr Glu Glu Leu Leu Val Lys Leu Asn Arg Glu Asp Leu Leu Arg 385 390 395 400 Lys Gln Arg Thr Phe Asp Asn Gly Ser Ile Pro His Gln Ile His Leu 405 410 415 Gly Glu Leu His Ala Ile Leu Arg Arg Gln Glu Asp Phe Tyr Pro Phe 420 425 430 Leu Lys Asp Asn Arg Glu Lys Ile Glu Lys Ile Leu Thr Phe Arg Ile 435 440 445 Pro Tyr Tyr Val Gly Pro Leu Ala Arg Gly Asn Ser Arg Phe Ala Trp 450 455 460 Met Thr Arg Lys Ser Glu Glu Thr Ile Thr Pro Trp Asn Phe Glu Glu 465 470 475 480 Val Val Asp Lys Gly Ala Ser Ala Gln Ser Phe Ile Glu Arg Met Thr 485 490 495 Asn Phe Asp Lys Asn Leu Pro Asn Glu Lys Val Leu Pro Lys His Ser 500 505 510 Leu Leu Tyr Glu Tyr Phe Thr Val Tyr Asn Glu Leu Thr Lys Val Lys 515 520 525 Tyr Val Thr Glu Gly Met Arg Lys Pro Ala Phe Leu Ser Gly Glu Gln 530 535 540 Lys Lys Ala Ile Val Asp Leu Leu Phe Lys Thr Asn Arg Lys Val Thr 545 550 555 560 Val Lys Gln Leu Lys Glu Asp Tyr Phe Lys Lys Ile Glu Cys Phe Asp 565 570 575 Ser Val Glu Ile Ser Gly Val Glu Asp Arg Phe Asn Ala Ser Leu Gly 580 585 590 Thr Tyr His Asp Leu Leu Lys Ile Ile Lys Asp Lys Asp Phe Leu Asp 595 600 605 Asn Glu Glu Asn Glu Asp Ile Leu Glu Asp Ile Val Leu Thr Leu Thr 610 615 620 Leu Phe Glu Asp Arg Glu Met Ile Glu Glu Arg Leu Lys Thr Tyr Ala 625 630 635 640 His Leu Phe Asp Asp Lys Val Met Lys Gln Leu Lys Arg Arg Arg Tyr 645 650 655 Thr Gly Trp Gly Arg Leu Ser Arg Lys Leu Ile Asn Gly Ile Arg Asp 660 665 670 Lys Gln Ser Gly Lys Thr Ile Leu Asp Phe Leu Lys Ser Asp Gly Phe 675 680 685 Ala Asn Arg Asn Phe Met Gln Leu Ile His Asp Asp Ser Leu Thr Phe 690 695 700 Lys Glu Asp Ile Gln Lys Ala Gln Val Ser Gly Gln Gly Asp Ser Leu 705 710 715 720 His Glu His Ile Ala Asn Leu Ala Gly Ser Pro Ala Ile Lys Lys Gly 725 730 735 Ile Leu Gln Thr Val Lys Val Val Asp Glu Leu Val Lys Val Met Gly 740 745 750 Arg His Lys Pro Glu Asn Ile Val Ile Glu Met Ala Arg Glu Asn Gln 755 760 765 Thr Thr Gln Lys Gly Gln Lys Asn Ser Arg Glu Arg Met Lys Arg Ile 770 775 780 Glu Glu Gly Ile Lys Glu Leu Gly Ser Gln Ile Leu Lys Glu His Pro 785 790 795 800 Val Glu Asn Thr Gln Leu Gln Asn Glu Lys Leu Tyr Leu Tyr Tyr Leu 805 810 815 Gln Asn Gly Arg Asp Met Tyr Val Asp Gln Glu Leu Asp Ile Asn Arg 820 825 830 Leu Ser Asp Tyr Asp Val Asp His Ile Val Pro Gln Ser Phe Leu Lys 835 840 845 Asp Asp Ser Ile Asp Asn Lys Val Leu Thr Arg Ser Asp Lys Asn Arg 850 855 860 Gly Lys Ser Asp Asn Val Pro Ser Glu Glu Val Val Lys Lys Met Lys 865 870 875 880 Asn Tyr Trp Arg Gln Leu Leu Asn Ala Lys Leu Ile Thr Gln Arg Lys 885 890 895 Phe Asp Asn Leu Thr Lys Ala Glu Arg Gly Gly Leu Ser Glu Leu Asp 900 905 910 Lys Ala Gly Phe Ile Lys Arg Gln Leu Val Glu Thr Arg Gln Ile Thr 915 920 925 Lys His Val Ala Gln Ile Leu Asp Ser Arg Met Asn Thr Lys Tyr Asp 930 935 940 Glu Asn Asp Lys Leu Ile Arg Glu Val Lys Val Ile Thr Leu Lys Ser 945 950 955 960 Lys Leu Val Ser Asp Phe Arg Lys Asp Phe Gln Phe Tyr Lys Val Arg 965 970 975 Glu Ile Asn Asn Tyr His His Ala His Asp Ala Tyr Leu Asn Ala Val 980 985 990 Val Gly Thr Ala Leu Ile Lys Lys Tyr Pro Lys Leu Glu Ser Glu Phe 995 1000 1005 Val Tyr Gly Asp Tyr Lys Val Tyr Asp Val Arg Lys Met Ile Ala 1010 1015 1020 Lys Ser Glu Gln Glu Ile Gly Lys Ala Thr Ala Lys Tyr Phe Phe 1025 1030 1035 Tyr Ser Asn Ile Met Asn Phe Phe Lys Thr Glu Ile Thr Leu Ala 1040 1045 1050 Asn Gly Glu Ile Arg Lys Arg Pro Leu Ile Glu Thr Asn Gly Glu 1055 1060 1065 Thr Gly Glu Ile Val Trp Asp Lys Gly Arg Asp Phe Ala Thr Val 1070 1075 1080 Arg Lys Val Leu Ser Met Pro Gln Val Asn Ile Val Lys Lys Thr 1085 1090 1095 Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro Lys 1100 1105 1110 Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 1115 1120 1125 Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val Ala Tyr Ser Val 1130 1135 1140 Leu Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys 1145 1150 1155 Ser Val Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser 1160 1165 1170 Phe Glu Lys Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys 1175 1180 1185 Glu Val Lys Lys Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu 1190 1195 1200 Phe Glu Leu Glu Asn Gly Arg Lys Arg Met Leu Ala Ser Ala Gly 1205 1210 1215 Glu Leu Gln Lys Gly Asn Glu Leu Ala Leu Pro Ser Lys Tyr Val 1220 1225 1230 Asn Phe Leu Tyr Leu Ala Ser His Tyr Glu Lys Leu Lys Gly Ser 1235 1240 1245 Pro Glu Asp Asn Glu Gln Lys Gln Leu Phe Val Glu Gln His Lys 1250 1255 1260 His Tyr Leu Asp Glu Ile Ile Glu Gln Ile Ser Glu Phe Ser Lys 1265 1270 1275 Arg Val Ile Leu Ala Asp Ala Asn Leu Asp Lys Val Leu Ser Ala 1280 1285 1290 Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu Gln Ala Glu Asn 1295 1300 1305 Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala Pro Ala Ala 1310 1315 1320 Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Arg Tyr Thr Ser 1325 1330 1335 Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile Thr 1340 1345 1350 Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 1355 1360 1365 <210> 2 <211> 1053 <212> PRT <213> Staphylococcus aureus <400> 2 Met Lys Arg Asn Tyr Ile Leu Gly Leu Asp Ile Gly Ile Thr Ser Val 1 5 10 15 Gly Tyr Gly Ile Ile Asp Tyr Glu Thr Arg Asp Val Ile Asp Ala Gly 20 25 30 Val Arg Leu Phe Lys Glu Ala Asn Val Glu Asn Asn Glu Gly Arg Arg 35 40 45 Ser Lys Arg Gly Ala Arg Arg Leu Lys Arg Arg Arg Arg His Arg Ile 50 55 60 Gln Arg Val Lys Lys Leu Leu Phe Asp Tyr Asn Leu Leu Thr Asp His 65 70 75 80 Ser Glu Leu Ser Gly Ile Asn Pro Tyr Glu Ala Arg Val Lys Gly Leu 85 90 95 Ser Gln Lys Leu Ser Glu Glu Glu Phe Ser Ala Ala Leu Leu His Leu 100 105 110 Ala Lys Arg Arg Gly Val His Asn Val Asn Glu Val Glu Glu Asp Thr 115 120 125 Gly Asn Glu Leu Ser Thr Lys Glu Gln Ile Ser Arg Asn Ser Lys Ala 130 135 140 Leu Glu Glu Lys Tyr Val Ala Glu Leu Gln Leu Glu Arg Leu Lys Lys 145 150 155 160 Asp Gly Glu Val Arg Gly Ser Ile Asn Arg Phe Lys Thr Ser Asp Tyr 165 170 175 Val Lys Glu Ala Lys Gln Leu Leu Lys Val Gln Lys Ala Tyr His Gln 180 185 190 Leu Asp Gln Ser Phe Ile Asp Thr Tyr Ile Asp Leu Leu Glu Thr Arg 195 200 205 Arg Thr Tyr Tyr Glu Gly Pro Gly Glu Gly Ser Pro Phe Gly Trp Lys 210 215 220 Asp Ile Lys Glu Trp Tyr Glu Met Leu Met Gly His Cys Thr Tyr Phe 225 230 235 240 Pro Glu Glu Leu Arg Ser Val Lys Tyr Ala Tyr Asn Ala Asp Leu Tyr 245 250 255 Asn Ala Leu Asn Asp Leu Asn Asn Leu Val Ile Thr Arg Asp Glu Asn 260 265 270 Glu Lys Leu Glu Tyr Tyr Glu Lys Phe Gln Ile Ile Glu Asn Val Phe 275 280 285 Lys Gln Lys Lys Lys Pro Thr Leu Lys Gln Ile Ala Lys Glu Ile Leu 290 295 300 Val Asn Glu Glu Asp Ile Lys Gly Tyr Arg Val Thr Ser Thr Gly Lys 305 310 315 320 Pro Glu Phe Thr Asn Leu Lys Val Tyr His Asp Ile Lys Asp Ile Thr 325 330 335 Ala Arg Lys Glu Ile Ile Glu Asn Ala Glu Leu Leu Asp Gln Ile Ala 340 345 350 Lys Ile Leu Thr Ile Tyr Gln Ser Ser Glu Asp Ile Gln Glu Glu Leu 355 360 365 Thr Asn Leu Asn Ser Glu Leu Thr Gln Glu Glu Ile Glu Gln Ile Ser 370 375 380 Asn Leu Lys Gly Tyr Thr Gly Thr His Asn Leu Ser Leu Lys Ala Ile 385 390 395 400 Asn Leu Ile Leu Asp Glu Leu Trp His Thr Asn Asp Asn Gln Ile Ala 405 410 415 Ile Phe Asn Arg Leu Lys Leu Val Pro Lys Lys Val Asp Leu Ser Gln 420 425 430 Gln Lys Glu Ile Pro Thr Thr Leu Val Asp Asp Phe Ile Leu Ser Pro 435 440 445 Val Val Lys Arg Ser Phe Ile Gln Ser Ile Lys Val Ile Asn Ala Ile 450 455 460 Ile Lys Lys Tyr Gly Leu Pro Asn Asp Ile Ile Ile Glu Leu Ala Arg 465 470 475 480 Glu Lys Asn Ser Lys Asp Ala Gln Lys Met Ile Asn Glu Met Gln Lys 485 490 495 Arg Asn Arg Gln Thr Asn Glu Arg Ile Glu Glu Ile Ile Arg Thr Thr 500 505 510 Gly Lys Glu Asn Ala Lys Tyr Leu Ile Glu Lys Ile Lys Leu His Asp 515 520 525 Met Gln Glu Gly Lys Cys Leu Tyr Ser Leu Glu Ala Ile Pro Leu Glu 530 535 540 Asp Leu Leu Asn Asn Pro Phe Asn Tyr Glu Val Asp His Ile Ile Pro 545 550 555 560 Arg Ser Val Ser Phe Asp Asn Ser Phe Asn Asn Lys Val Leu Val Lys 565 570 575 Gln Glu Glu Asn Ser Lys Lys Gly Asn Arg Thr Pro Phe Gln Tyr Leu 580 585 590 Ser Ser Ser Asp Ser Lys Ile Ser Tyr Glu Thr Phe Lys Lys His Ile 595 600 605 Leu Asn Leu Ala Lys Gly Lys Gly Arg Ile Ser Lys Thr Lys Lys Glu 610 615 620 Tyr Leu Leu Glu Glu Arg Asp Ile Asn Arg Phe Ser Val Gln Lys Asp 625 630 635 640 Phe Ile Asn Arg Asn Leu Val Asp Thr Arg Tyr Ala Thr Arg Gly Leu 645 650 655 Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn Asn Leu Asp Val Lys 660 665 670 Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe Leu Arg Arg Lys Trp 675 680 685 Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys His His Ala Glu Asp 690 695 700 Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys 705 710 715 720 Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln Met Phe Glu Glu Lys 725 730 735 Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu 740 745 750 Ile Phe Ile Thr Pro His Gln Ile Lys His Ile Lys Asp Phe Lys Asp 755 760 765 Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro Asn Arg Glu Leu Ile 770 775 780 Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu 785 790 795 800 Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu 805 810 815 Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu Leu Met Tyr His His 820 825 830 Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly 835 840 845 Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr 850 855 860 Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro Val Ile Lys Lys Ile 865 870 875 880 Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu Asp Ile Thr Asp Asp 885 890 895 Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu Ser Leu Lys Pro Tyr 900 905 910 Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr Lys Phe Val Thr Val 915 920 925 Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser 930 935 940 Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala 945 950 955 960 Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly 965 970 975 Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp Leu Leu Asn Arg Ile 980 985 990 Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met 995 1000 1005 Asn Asp Lys Arg Pro Pro Arg Ile Ile Lys Thr Ile Ala Ser Lys 1010 1015 1020 Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu Gly Asn Leu 1025 1030 1035 Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys Lys Gly 1040 1045 1050 <210> 3 <211> 6 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (1)..(2) <223> a, c, t, g, unknown or other <400> 3 nnagaa 6 <210> 4 <211> 6 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (1)..(2) <223> a, c, t, g, unknown or other <400> 4 nngggt 6 <210> 5 <211> 6 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (1)..(2) <223> a, c, t, g, unknown or other <400> 5 nngagt 6 <210> 6 <211> 6 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (1)..(2) <223> a, c, t, g, unknown or other <400> 6 nngaat 6 <210> 7 <211> 4572 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 7 taatacgact cactataggg gaattgtgag cggataacaa ttcccctgta gaaataattt 60 tgtttaactt taataaggag atataccatg gataaaaagt attctattgg tttagacatc 120 ggcactaatt ccgttggatg ggctgtcata accgatgaat acaaagtacc ttcaaagaaa 180 tttaaggtgt tggggaacac agaccgtcat tcgattaaaa agaatcttat cggtgccctc 240 ctattcgata gtggcgaaac ggcagaggcg actcgcctga aacgaaccgc tcggagaagg 300 tatacacgtc gcaagaaccg aatatgttac ttacaagaaa tttttagcaa tgagatggcc 360 aaagttgacg attctttctt tcaccgtttg gaagagtcct tccttgtcga agaggacaag 420 aaacatgaac ggcaccccat ctttggaaac atagtagatg aggtggcata tcatgaaaag 480 tacccaacga tttatcacct cagaaaaaag ctagttgact caactgataa agcggacctg 540 aggttaatct acttggctct tgcccatatg ataaagttcc gtgggcactt tctcattgag 600 ggtgatctaa atccggacaa ctcggatgtc gacaaactgt tcatccagtt agtacaaacc 660 tataatcagt tgtttgaaga gaaccctata aatgcaagtg gcgtggatgc gaaggctatt 720 cttagcgccc gcctctctaa atcccgacgg ctagaaaacc tgatcgcaca attacccgga 780 gagaagaaaa atgggttgtt cggtaacctt atagcgctct cactaggcct gacaccaaat 840 tttaagtcga acttcgactt agctgaagat gccaaattgc agcttagtaa ggacacgtac 900 gatgacgatc tcgacaatct actggcacaa attggagatc agtatgcgga cttatttttg 960 gctgccaaaa accttagcga tgcaatcctc ctatctgaca tactgagagt taatactgag 1020 attaccaagg cgccgttatc cgcttcaatg atcaaaaggt acgatgaaca tcaccaagac 1080 ttgacacttc tcaaggccct agtccgtcag caactgcctg agaaatataa ggaaatattc 1140 tttgatcagt cgaaaaacgg gtacgcaggt tatattgacg gcggagcgag tcaagaggaa 1200 ttctacaagt ttatcaaacc catattagag aagatggatg ggacggaaga gttgcttgta 1260 aaactcaatc gcgaagatct actgcgaaag cagcggactt tcgacaacgg tagcattcca 1320 catcaaatcc acttaggcga attgcatgct atacttagaa ggcaggagga tttttatccg 1380 ttcctcaaag acaatcgtga aaagattgag aaaatcctaa cctttcgcat accttactat 1440 gtgggacccc tggcccgagg gaactctcgg ttcgcatgga tgacaagaaa gtccgaagaa 1500 acgattactc cctggaattt tgaggaagtt gtcgataaag gtgcgtcagc tcaatcgttc 1560 atcgagagga tgaccaactt tgacaagaat ttaccgaacg aaaaagtatt gcctaagcac 1620 agtttacttt acgagtattt cacagtgtac aatgaactca cgaaagttaa gtatgtcact 1680 gagggcatgc gtaaacccgc ctttctaagc ggagaacaga agaaagcaat agtagatctg 1740 ttattcaaga ccaaccgcaa agtgacagtt aagcaattga aagaggacta ctttaagaaa 1800 attgaatgct tcgattctgt cgagatctcc ggggtagaag atcgatttaa tgcgtcactt 1860 ggtacgtatc atgacctcct aaagataatt aaagataagg acttcctgga taacgaagag 1920 aatgaagata tcttagaaga tatagtgttg actcttaccc tctttgaaga tcgggaaatg 1980 attgaggaaa gactaaaaac atacgctcac ctgttcgacg ataaggttat gaaacagtta 2040 aagaggcgtc gctatacggg ctggggacga ttgtcgcgga aacttatcaa cgggataaga 2100 gacaagcaaa gtggtaaaac tattctcgat tttctaaaga gcgacggctt cgccaatagg 2160 aactttatgc agctgatcca tgatgactct ttaaccttca aagaggatat acaaaaggca 2220 caggtttccg gacaagggga ctcattgcac gaacatattg cgaatcttgc tggttcgcca 2280 gccatcaaaa agggcatact ccagacagtc aaagtagtgg atgagctagt taaggtcatg 2340 ggacgtcaca aaccggaaaa cattgtaatc gagatggcac gcgaaaatca aacgactcag 2400 aaggggcaaa aaaacagtcg agagcggatg aagagaatag aagagggtat taaagaactg 2460 ggcagccaga tcttaaagga gcatcctgtg gaaaataccc aattgcagaa cgagaaactt 2520 tacctctatt acctacaaaa tggaagggac atgtatgttg atcaggaact ggacataaac 2580 cgtttatctg attacgacgt cgatcacatt gtaccccaat cctttttgaa ggacgattca 2640 atcgacaata aagtgcttac acgctcggat aagaaccgag ggaaaagtga caatgttcca 2700 agcgaggaag tcgtaaagaa aatgaagaac tattggcggc agctcctaaa tgcgaaactg 2760 ataacgcaaa gaaagttcga taacttaact aaagctgaga ggggtggctt gtctgaactt 2820 gacaaggccg gatttattaa acgtcagctc gtggaaaccc gccaaatcac aaagcatgtt 2880 gcacagatac tagattcccg aatgaatacg aaatacgacg agaacgataa gctgattcgg 2940 gaagtcaaag taatcacttt aaagtcaaaa ttggtgtcgg acttcagaaa ggattttcaa 3000 ttctataaag ttagggagat aaataactac caccatgcgc acgacgctta tcttaatgcc 3060 gtcgtaggga ccgcactcat taagaaatac ccgaagctag aaagtgagtt tgtgtatggt 3120 gattacaaag tttatgacgt ccgtaagatg atcgcgaaaa gcgaacagga gataggcaag 3180 gctacagcca aatacttctt ttattctaac attatgaatt tctttaagac ggaaatcact 3240 ctggcaaacg gagagatacg caaacgacct ttaattgaaa ccaatgggga gacaggtgaa 3300 atcgtatggg ataagggccg ggacttcgcg acggtgagaa aagttttgtc catgccccaa 3360 gtcaacatag taaagaaaac tgaggtgcag accggagggt tttcaaagga atcgattctt 3420 ccaaaaagga atagtgataa gctcatcgct cgtaaaaagg actgggaccc gaaaaagtac 3480 ggtggcttcg atagccctac agttgcctat tctgtcctag tagtggcaaa agttgagaag 3540 ggaaaatcca agaaactgaa gtcagtcaaa gaattattgg ggataacgat tatggagcgc 3600 tcgtcttttg aaaagaaccc catcgacttc cttgaggcga aaggttacaa ggaagtaaaa 3660 aaggatctca taattaaact accaaagtat agtctgtttg agttagaaaa tggccgaaaa 3720 cggatgttgg ctagcgccgg agagcttcaa aaggggaacg aactcgcact accgtctaaa 3780 tacgtgaatt tcctgtattt agcgtcccat tacgagaagt tgaaaggttc acctgaagat 3840 aacgaacaga agcaactttt tgttgagcag cacaaacatt atctcgacga aatcatagag 3900 caaatttcgg aattcagtaa gagagtcatc ctagctgatg ccaatctgga caaagtatta 3960 agcgcataca acaagcacag ggataaaccc atacgtgagc aggcggaaaa tattatccat 4020 ttgtttactc ttaccaacct cggcgctcca gccgcattca agtattttga cacaacgata 4080 gatcgcaaac gatacacttc taccaaggag gtgctagacg cgacactgat tcaccaatcc 4140 atcacgggat tatatgaaac tcggatagat ttgtcacagc ttgggggtga cggatccccc 4200 aagaagaaga ggaaagtctc gagcgactac aaagaccatg acggtgatta taaagatcat 4260 gacatcgatt acaaggatga cgatgacaag tgaagcggcc gcataatgct taagtcgaac 4320 agaaagtaat cgtattgtac acggccgcat aatcgaaatt aatacgactc actataggga 4380 gacccatgcc atagcgttgt tcggaacaga ttcaccaaca cctagtggtc tccgttttag 4440 agctagaaat agcaagttaa aataaggcta gtccgttatc aacttgaaaa agtggcaccg 4500 agtcggtgct ccgctgagca ataactagca taaccccttg gggcctctaa acgggtcttg 4560 aggggttttt tg 4572 <210> 8 <211> 4572 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 8 taatacgact cactataggg gaattgtgag cggataacaa ttcccctgta gaaataattt 60 tgtttaactt taataaggag atataccatg gataaaaagt attctattgg tttagccatc 120 ggcactaatt ccgttggatg ggctgtcata accgatgaat acaaagtacc ttcaaagaaa 180 tttaaggtgt tggggaacac agaccgtcat tcgattaaaa agaatcttat cggtgccctc 240 ctattcgata gtggcgaaac ggcagaggcg actcgcctga aacgaaccgc tcggagaagg 300 tatacacgtc gcaagaaccg aatatgttac ttacaagaaa tttttagcaa tgagatggcc 360 aaagttgacg attctttctt tcaccgtttg gaagagtcct tccttgtcga agaggacaag 420 aaacatgaac ggcaccccat ctttggaaac atagtagatg aggtggcata tcatgaaaag 480 tacccaacga tttatcacct cagaaaaaag ctagttgact caactgataa agcggacctg 540 aggttaatct acttggctct tgcccatatg ataaagttcc gtgggcactt tctcattgag 600 ggtgatctaa atccggacaa ctcggatgtc gacaaactgt tcatccagtt agtacaaacc 660 tataatcagt tgtttgaaga gaaccctata aatgcaagtg gcgtggatgc gaaggctatt 720 cttagcgccc gcctctctaa atcccgacgg ctagaaaacc tgatcgcaca attacccgga 780 gagaagaaaa atgggttgtt cggtaacctt atagcgctct cactaggcct gacaccaaat 840 tttaagtcga acttcgactt agctgaagat gccaaattgc agcttagtaa ggacacgtac 900 gatgacgatc tcgacaatct actggcacaa attggagatc agtatgcgga cttatttttg 960 gctgccaaaa accttagcga tgcaatcctc ctatctgaca tactgagagt taatactgag 1020 attaccaagg cgccgttatc cgcttcaatg atcaaaaggt acgatgaaca tcaccaagac 1080 ttgacacttc tcaaggccct agtccgtcag caactgcctg agaaatataa ggaaatattc 1140 tttgatcagt cgaaaaacgg gtacgcaggt tatattgacg gcggagcgag tcaagaggaa 1200 ttctacaagt ttatcaaacc catattagag aagatggatg ggacggaaga gttgcttgta 1260 aaactcaatc gcgaagatct actgcgaaag cagcggactt tcgacaacgg tagcattcca 1320 catcaaatcc acttaggcga attgcatgct atacttagaa ggcaggagga tttttatccg 1380 ttcctcaaag acaatcgtga aaagattgag aaaatcctaa cctttcgcat accttactat 1440 gtgggacccc tggcccgagg gaactctcgg ttcgcatgga tgacaagaaa gtccgaagaa 1500 acgattactc cctggaattt tgaggaagtt gtcgataaag gtgcgtcagc tcaatcgttc 1560 atcgagagga tgaccaactt tgacaagaat ttaccgaacg aaaaagtatt gcctaagcac 1620 agtttacttt acgagtattt cacagtgtac aatgaactca cgaaagttaa gtatgtcact 1680 gagggcatgc gtaaacccgc ctttctaagc ggagaacaga agaaagcaat agtagatctg 1740 ttattcaaga ccaaccgcaa agtgacagtt aagcaattga aagaggacta ctttaagaaa 1800 attgaatgct tcgattctgt cgagatctcc ggggtagaag atcgatttaa tgcgtcactt 1860 ggtacgtatc atgacctcct aaagataatt aaagataagg acttcctgga taacgaagag 1920 aatgaagata tcttagaaga tatagtgttg actcttaccc tctttgaaga tcgggaaatg 1980 attgaggaaa gactaaaaac atacgctcac ctgttcgacg ataaggttat gaaacagtta 2040 aagaggcgtc gctatacggg ctggggacga ttgtcgcgga aacttatcaa cgggataaga 2100 gacaagcaaa gtggtaaaac tattctcgat tttctaaaga gcgacggctt cgccaatagg 2160 aactttatgc agctgatcca tgatgactct ttaaccttca aagaggatat acaaaaggca 2220 caggtttccg gacaagggga ctcattgcac gaacatattg cgaatcttgc tggttcgcca 2280 gccatcaaaa agggcatact ccagacagtc aaagtagtgg atgagctagt taaggtcatg 2340 ggacgtcaca aaccggaaaa cattgtaatc gagatggcac gcgaaaatca aacgactcag 2400 aaggggcaaa aaaacagtcg agagcggatg aagagaatag aagagggtat taaagaactg 2460 ggcagccaga tcttaaagga gcatcctgtg gaaaataccc aattgcagaa cgagaaactt 2520 tacctctatt acctacaaaa tggaagggac atgtatgttg atcaggaact ggacataaac 2580 cgtttatctg attacgacgt cgatgccatt gtaccccaat cctttttgaa ggacgattca 2640 atcgacaata aagtgcttac acgctcggat aagaaccgag ggaaaagtga caatgttcca 2700 agcgaggaag tcgtaaagaa aatgaagaac tattggcggc agctcctaaa tgcgaaactg 2760 ataacgcaaa gaaagttcga taacttaact aaagctgaga ggggtggctt gtctgaactt 2820 gacaaggccg gatttattaa acgtcagctc gtggaaaccc gccaaatcac aaagcatgtt 2880 gcacagatac tagattcccg aatgaatacg aaatacgacg agaacgataa gctgattcgg 2940 gaagtcaaag taatcacttt aaagtcaaaa ttggtgtcgg acttcagaaa ggattttcaa 3000 ttctataaag ttagggagat aaataactac caccatgcgc acgacgctta tcttaatgcc 3060 gtcgtaggga ccgcactcat taagaaatac ccgaagctag aaagtgagtt tgtgtatggt 3120 gattacaaag tttatgacgt ccgtaagatg atcgcgaaaa gcgaacagga gataggcaag 3180 gctacagcca aatacttctt ttattctaac attatgaatt tctttaagac ggaaatcact 3240 ctggcaaacg gagagatacg caaacgacct ttaattgaaa ccaatgggga gacaggtgaa 3300 atcgtatggg ataagggccg ggacttcgcg acggtgagaa aagttttgtc catgccccaa 3360 gtcaacatag taaagaaaac tgaggtgcag accggagggt tttcaaagga atcgattctt 3420 ccaaaaagga atagtgataa gctcatcgct cgtaaaaagg actgggaccc gaaaaagtac 3480 ggtggcttcg atagccctac agttgcctat tctgtcctag tagtggcaaa agttgagaag 3540 ggaaaatcca agaaactgaa gtcagtcaaa gaattattgg ggataacgat tatggagcgc 3600 tcgtcttttg aaaagaaccc catcgacttc cttgaggcga aaggttacaa ggaagtaaaa 3660 aaggatctca taattaaact accaaagtat agtctgtttg agttagaaaa tggccgaaaa 3720 cggatgttgg ctagcgccgg agagcttcaa aaggggaacg aactcgcact accgtctaaa 3780 tacgtgaatt tcctgtattt agcgtcccat tacgagaagt tgaaaggttc acctgaagat 3840 aacgaacaga agcaactttt tgttgagcag cacaaacatt atctcgacga aatcatagag 3900 caaatttcgg aattcagtaa gagagtcatc ctagctgatg ccaatctgga caaagtatta 3960 agcgcataca acaagcacag ggataaaccc atacgtgagc aggcggaaaa tattatccat 4020 ttgtttactc ttaccaacct cggcgctcca gccgcattca agtattttga cacaacgata 4080 gatcgcaaac gatacacttc taccaaggag gtgctagacg cgacactgat tcaccaatcc 4140 atcacgggat tatatgaaac tcggatagat ttgtcacagc ttgggggtga cggatccccc 4200 aagaagaaga ggaaagtctc gagcgactac aaagaccatg acggtgatta taaagatcat 4260 gacatcgatt acaaggatga cgatgacaag tgaagcggcc gcataatgct taagtcgaac 4320 agaaagtaat cgtattgtac acggccgcat aatcgaaatt aatacgactc actataggga 4380 gacccatgcc atagcgttgt tcggaacaga ttcaccaaca cctagtggtc tccgttttag 4440 agctagaaat agcaagttaa aataaggcta gtccgttatc aacttgaaaa agtggcaccg 4500 agtcggtgct ccgctgagca ataactagca taaccccttg gggcctctaa acgggtcttg 4560 aggggttttt tg 4572 <210> 9 <211> 3825 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 9 taatacgact cactataggg gaattgtgag cggataacaa ttcccctgta gaaataattt 60 tgtttaactt taataaggag atataccatg ggcagcgacc tggtgctggg cctggacatc 120 ggcatcggca gcgtgggcgt gggcatcctg aacaaggtga ccggcgagat catccacaag 180 aacagtcgca tcttccctgc tgctcaggct gagaacaacc tggtgcgccg caccaaccgc 240 cagggtcgcc ggcttgctcg ccgcaagaag caccggcgcg tgcgcctgaa ccgcctgttc 300 gaggagagcg gcctgatcac cgacttcacc aagatcagca tcaacctgaa cccctaccag 360 ctgcgcgtga agggcctgac cgacgagctg agcaacgagg agctgttcat cgccctgaag 420 aacatggtga agcaccgcgg catcagctac ctggacgacg ccagcgacga cggcaacagc 480 agcgtgggcg actacgccca gatcgtgaag gagaacagca agcagctgga gaccaagacc 540 cccggccaga tccagctgga gcgctaccag acctacggcc agctgcgcgg cgacttcacc 600 gtggagaagg acggcaagaa gcaccgcctg atcaacgtgt tccccaccag cgcctaccgc 660 agcgaggccc tgcgcatcct gcagacccag caggagttca acccccagat caccgacgag 720 ttcatcaacc gctacctgga gatcctgacc ggcaagcgca agtactacca cggccccggc 780 aacgagaaga gccgcaccga ctacggccgc taccgcacca gcggcgagac cctggacaac 840 atcttcggca tcctgatcgg caagtgcacc ttctaccccg acgagttccg cgccgccaag 900 gccagctaca ccgcccagga gttcaatctg ctgaacgacc tgaacaacct gaccgtgccc 960 accgagacca agaagctgag caaggagcag aagaaccaga tcatcaacta cgtgaagaac 1020 gagaaggcta tgggccccgc caagctgttc aagtacatcg ccaagctgct gagctgcgac 1080 gtggccgaca tcaagggcta ccgcatcgac aagagcggca aggccgagat ccacaccttc 1140 gaggcctacc gcaagatgaa gaccctggag accctggaca tcgagcagat ggaccgagag 1200 accctggaca agctggccta cgtgctgacc ctgaacaccg agcgcgaggg catccaggag 1260 gccctggagc acgagttcgc cgacggcagc ttcagccaga aacaggtgga cgagctggtg 1320 cagttccgca aggccaacag cagcatcttc ggcaagggct ggcacaactt cagcgtgaag 1380 ctgatgatgg agctgatccc cgagctgtac gagaccagcg aggagcagat gaccatcctg 1440 acccgcctgg gcaagcagaa gaccaccagc agcagcaaca agaccaagta catcgacgag 1500 aagctgctga ccgaggagat ctacaacccc gtggtggcca agagcgtgcg ccaggccatc 1560 aagatcgtga acgccgccat caaggagtac ggcgacttcg acaacatcgt gatcgagatg 1620 gcccgcgaga ccaacgagga cgacgagaag aaggccatcc agaagatcca gaaggccaac 1680 aaggacgaga aggacgccgc catgctgaag gccgccaacc agtacaacgg caaggccgag 1740 ctgccccaca gcgtgttcca cggccacaag cagctggcca ccaagatccg cctgtggcac 1800 cagcagggcg agcgctgcct gtacaccggc aagaccatca gcatccacga cctgatcaac 1860 aacagcaacc agttcgaggt ggaccacatc ctgcccctga gcatcacctt cgacgacagc 1920 ctggccaaca aggtgctggt gtacgccacc gccaaccagg agaagggcca gcgcaccccc 1980 taccaggccc tggacagcat ggacgacgcc tggagcttcc gcgagctgaa ggccttcgtg 2040 cgcgagagca agaccctgag caacaagaag aaggagtatc tgctgaccga ggaggacatc 2100 agcaagttcg acgtgcgcaa gaagttcatc gagcgcaacc tggtggacac ccgctacgcc 2160 agccgcgtgg tgctgaacgc cctgcaggag cacttccgcg cccacaagat cgacaccaag 2220 gtgagcgtgg tgcgcggcca gttcaccagc cagctgcgcc gccactgggg catcgagaag 2280 acccgcgaca cctaccacca ccacgccgtg gacgccctga tcattgcggc ttctagccag 2340 ctgaacctgt ggaagaagca gaagaacacc ctggtgagct acagcgagga ccagctgctg 2400 gacatcgaga ccggcgagct gatcagcgac gacgagtaca aggagagcgt gttcaaggcc 2460 ccctaccagc acttcgtgga caccctgaag agcaaggagt tcgaggacag catcctgttc 2520 agctaccagg tggacagcaa gttcaaccgc aagatcagcg acgccaccat ctacgccacc 2580 cgccaggcca aggtgggcaa ggacaaggcc gacgagacct acgtgctggg caagatcaag 2640 gacatctaca cccaggacgg ctacgacgcc ttcatgaaga tctacaagaa ggacaagagc 2700 aagttcctga tgtaccgcca cgacccccag accttcgaga aggtgatcga gcccatcctg 2760 gagaactacc ccaacaagca gatcaacgat aaaggcaagg aggtgccctg caaccccttc 2820 ctgaagtaca aggaggagca cggctacatc cgcaagtaca gcaagaaggg caacggcccc 2880 gagatcaaga gcctgaagta ctacgacagc aagctgggca accacatcga catcaccccc 2940 aaggacagca acaacaaggt ggtgctgcag agcgtgagcc cctggcgcgc cgacgtgtac 3000 ttcaacaaga ccaccggcaa gtacgagatc ctggggctga agtacgccga tctgcagttt 3060 gataaaggca caggcaccta caagatcagc caggagaagt acaacgacat caagaagaag 3120 gagggcgtgg acagcgacag cgagttcaag ttcaccctgt acaagaacga ccttctgctg 3180 gtgaaggaca ccgagaccaa ggagcaacag ctgttccgct tcctgagccg caccatgccc 3240 aagcagaagc actacgtgga gctgaagccc tacgacaagc agaagttcga gggcggcgag 3300 gccctgatca aggtgctggg caacgtggcc aacagcggcc agtgcaagaa gggcctgggc 3360 aagagcaaca tcagcatcta caaggtgcgc accgacgtgc tgggcaacca gcacatcatc 3420 aagaacgagg gcgacaagcc caagttggac ttcagcaggg ctgaccccaa gaagaagagg 3480 aaggtgtgag cggccgcata atgcttaagt cgaacagaaa gtaatcgtat tgtacacggc 3540 cgcataatcg aaattaatac gactcactat aggactgcag gtcatgccat agcgttgttc 3600 ggaacagatt caccaacacc tagtacctgc actcgttttt gtactctcaa gatttaagta 3660 actgtacaac gaaacttaca cagttactta aatcttgcag aagctacaaa gataaggctt 3720 catgccgaaa tcaacaccct gtcattttat ggcagggtgt tttccgctga gcaataacta 3780 gcataacccc ttggggcctc taaacgggtc ttgaggggtt ttttg 3825 <210> 10 <211> 3674 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 10 taatacgact cactataggg gaattgtgag cggataacaa ttcccctgta gaaataattt 60 tgtttaactt taataaggag atataccatg ggcaaacgga actacatcct ggggcttgac 120 attgggataa ccagcgttgg ctacggaatt attgattatg agacacgcga tgtgattgac 180 gccggggtta ggctgttcaa agaggccaac gttgaaaaca acgagggaag acggagtaag 240 cgcggagcaa gaagactcaa gcgcagacgg agacatcgga ttcagagggt gaaaaagctg 300 ctcttcgatt acaatctcct gaccgatcat agtgagctga gcggaatcaa cccctacgag 360 gcgcgagtga aagggctttc ccagaagctg tccgaagagg agttctccgc cgcgttgctg 420 cacctggcca aacggagggg ggttcacaat gtaaacgaag tggaggagga cacgggcaat 480 gaacttagta cgaaagaaca gatcagtagg aactctaagg ctctcgaaga gaaatacgtc 540 gctgagttgc agcttgagag actgaaaaaa gacggcgaag tacgcggatc tattaatagg 600 ttcaagactt cagattacgt aaaggaagcc aagcagctcc tgaaagtaca gaaagcgtac 660 catcagctcg atcagagctt catcgatacc tacatagatt tgctggagac acggaggaca 720 tactacgagg gcccagggga aggatctcct tttgggtgga aggacatcaa ggaatggtac 780 gagatgctta tgggacattg tacatatttt ccggaggagc tcaggagcgt caagtacgcc 840 tacaatgccg acctgtacaa tgccctcaat gacctcaata acctcgtgat taccagggac 900 gagaacgaga agctggagta ctatgaaaag ttccagatta tcgagaatgt gtttaagcag 960 aagaagaagc cgacacttaa gcagattgca aaggaaatcc tcgtgaatga ggaagatatc 1020 aagggataca gagtgacaag tacaggcaag cccgagttca caaatctgaa ggtgtaccac 1080 gatattaagg acataaccgc acgaaaggag ataatcgaaa acgctgagct cctcgatcag 1140 atcgcaaaaa ttcttaccat ctaccagtct agtgaggaca ttcaggagga actgactaat 1200 ctgaacagtg agctcaccca agaggaaatt gagcagattt caaacctgaa aggctacacc 1260 gggacgcaca atctgagcct caaagcaatc aacctcattc tggatgaact ttggcacaca 1320 aatgacaacc aaattgccat attcaaccgc ctgaaactgg tgccaaaaaa agtggatctg 1380 tcacagcaaa aggaaatccc tacaaccttg gttgacgatt ttattctgtc ccccgttgtc 1440 aagcggagct tcatccagtc aatcaaggtg atcaatgcca tcattaaaaa atacggattg 1500 ccaaacgata taattatcga gcttgcacga gagaagaact caaaggacgc ccagaagatg 1560 attaacgaaa tgcagaagcg caaccgccag acaaacgaac gcatagagga aattataaga 1620 acaaccggca aagagaatgc caagtatctg atcgagaaaa tcaagctgca cgacatgcaa 1680 gaaggcaagt gcctgtactc tctggaagct atcccactcg aagatctgct gaataatcca 1740 ttcaattacg aggtggacca catcatccct agatccgtaa gctttgacaa ttccttcaat 1800 aacaaagttc tggttaaaca ggaggaaaat tctaaaaaag ggaaccggac cccgttccag 1860 tacctgagct ccagtgacag caagattagc tacgagactt ttaagaaaca tattctgaat 1920 ctggccaaag gcaaaggcag gatcagcaag accaagaagg agtacctcct cgaagaacgc 1980 gacattaaca gatttagtgt gcagaaagat ttcatcaacc gaaaccttgt cgatactcgg 2040 tacgccacga gaggcctgat gaatctcctc aggagctact tccgcgtcaa taatctggac 2100 gttaaagtca agagcataaa tgggggattc accagctttc tgaggagaaa gtggaagttt 2160 aagaaggaac gaaacaaagg atacaagcac catgctgagg atgctttgat catcgctaac 2220 gcggacttta tctttaagga atggaaaaag ctggataagg caaagaaagt gatggaaaac 2280 cagatgttcg aggagaagca ggcagagtca atgcctgaga tcgagacaga gcaggaatac 2340 aaggaaattt tcatcacccc tcatcagatt aaacacataa aggacttcaa agactataaa 2400 tactctcata gggtggacaa aaaacccaat cgcgagctca ttaatgacac cctgtactca 2460 acacggaagg atgataaagg taataccttg attgtgaata atcttaatgg attgtatgac 2520 aaagataacg acaagctcaa gaagctgatc aacaagtctc cagagaagct ccttatgtat 2580 caccacgacc cacagactta tcagaaattg aaactgatca tggagcaata cggggatgag 2640 aagaacccac tctacaaata ttatgaggaa acaggtaatt acctgaccaa gtactccaag 2700 aaggataacg gaccagtgat caaaaagata aagtactatg gcaacaaact taatgcgcat 2760 ttggacataa ctgacgatta ccccaattct cgaaacaagg ttgtgaagct ctccctgaag 2820 ccttatagat ttgacgtgta cctggataat ggggtttata aattcgtcac cgtgaaaaat 2880 ctggacgtga tcaaaaagga gaactattat gaagtaaact caaagtgcta tgaggaggcg 2940 aagaagctga agaagatctc caatcaggcc gagttcatcg cttccttcta taataacgat 3000 ctcatcaaga tcaatggaga gctttatcgc gtcattggtg tgaacaatga cttgctgaac 3060 aggatcgaag tcaatatgat agacattacc taccgggagt atctcgaaaa catgaatgat 3120 aaacggccgc ctcgcatcat caagacaatc gcatctaaaa ctcagtcaat aaaaaagtac 3180 tctaccgata tcctggggaa tctctatgaa gtgaagtcaa agaagcaccc acaaatcatt 3240 aaaaaaggtg gatcccccaa gaagaagagg aaagtctcga gcgactacaa agaccatgac 3300 ggtgattata aagatcatga catcgattac aaggatgacg atgacaagta aagcggccgc 3360 ataatgctta agtcgaacag aaagtaatcg tattgtacac ggccgcataa tcgaaattaa 3420 tacgactcac tatagggaga cccatgccat agcgttgttc ggaacagatt caccaacacc 3480 tagtggtctc cgttttagta ctctgtaatt ttaggtatga ggtagacgaa aattgtactt 3540 atacctaaaa ttacagaatc tactaaaaca aggcaaaatg ccgtgtttat ctcgtcaact 3600 tgttggcgag atccgctgag caataactag cataacccct tggggcctct aaacgggtct 3660 tgaggggttt tttg 3674 <210> 11 <211> 4206 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 11 atggataaaa agtattctat tggtttagac atcggcacta attccgttgg atgggctgtc 60 ataaccgatg aatacaaagt accttcaaag aaatttaagg tgttggggaa cacagaccgt 120 cattcgatta aaaagaatct tatcggtgcc ctcctattcg atagtggcga aacggcagag 180 gcgactcgcc tgaaacgaac cgctcggaga aggtatacac gtcgcaagaa ccgaatatgt 240 tacttacaag aaatttttag caatgagatg gccaaagttg acgattcttt ctttcaccgt 300 ttggaagagt ccttccttgt cgaagaggac aagaaacatg aacggcaccc catctttgga 360 aacatagtag atgaggtggc atatcatgaa aagtacccaa cgatttatca cctcagaaaa 420 aagctagttg actcaactga taaagcggac ctgaggttaa tctacttggc tcttgcccat 480 atgataaagt tccgtgggca ctttctcatt gagggtgatc taaatccgga caactcggat 540 gtcgacaaac tgttcatcca gttagtacaa acctataatc agttgtttga agagaaccct 600 ataaatgcaa gtggcgtgga tgcgaaggct attcttagcg cccgcctctc taaatcccga 660 cggctagaaa acctgatcgc acaattaccc ggagagaaga aaaatgggtt gttcggtaac 720 cttatagcgc tctcactagg cctgacacca aattttaagt cgaacttcga cttagctgaa 780 gatgccaaat tgcagcttag taaggacacg tacgatgacg atctcgacaa tctactggca 840 caaattggag atcagtatgc ggacttattt ttggctgcca aaaaccttag cgatgcaatc 900 ctcctatctg acatactgag agttaatact gagattacca aggcgccgtt atccgcttca 960 atgatcaaaa ggtacgatga acatcaccaa gacttgacac ttctcaaggc cctagtccgt 1020 cagcaactgc ctgagaaata taaggaaata ttctttgatc agtcgaaaaa cgggtacgca 1080 ggttatattg acggcggagc gagtcaagag gaattctaca agtttatcaa acccatatta 1140 gagaagatgg atgggacgga agagttgctt gtaaaactca atcgcgaaga tctactgcga 1200 aagcagcgga ctttcgacaa cggtagcatt ccacatcaaa tccacttagg cgaattgcat 1260 gctatactta gaaggcagga ggatttttat ccgttcctca aagacaatcg tgaaaagatt 1320 gagaaaatcc taacctttcg cataccttac tatgtgggac ccctggcccg agggaactct 1380 cggttcgcat ggatgacaag aaagtccgaa gaaacgatta ctccctggaa ttttgaggaa 1440 gttgtcgata aaggtgcgtc agctcaatcg ttcatcgaga ggatgaccaa ctttgacaag 1500 aatttaccga acgaaaaagt attgcctaag cacagtttac tttacgagta tttcacagtg 1560 tacaatgaac tcacgaaagt taagtatgtc actgagggca tgcgtaaacc cgcctttcta 1620 agcggagaac agaagaaagc aatagtagat ctgttattca agaccaaccg caaagtgaca 1680 gttaagcaat tgaaagagga ctactttaag aaaattgaat gcttcgattc tgtcgagatc 1740 tccggggtag aagatcgatt taatgcgtca cttggtacgt atcatgacct cctaaagata 1800 attaaagata aggacttcct ggataacgaa gagaatgaag atatcttaga agatatagtg 1860 ttgactctta ccctctttga agatcgggaa atgattgagg aaagactaaa aacatacgct 1920 cacctgttcg acgataaggt tatgaaacag ttaaagaggc gtcgctatac gggctgggga 1980 cgattgtcgc ggaaacttat caacgggata agagacaagc aaagtggtaa aactattctc 2040 gattttctaa agagcgacgg cttcgccaat aggaacttta tgcagctgat ccatgatgac 2100 tctttaacct tcaaagagga tatacaaaag gcacaggttt ccggacaagg ggactcattg 2160 cacgaacata ttgcgaatct tgctggttcg ccagccatca aaaagggcat actccagaca 2220 gtcaaagtag tggatgagct agttaaggtc atgggacgtc acaaaccgga aaacattgta 2280 atcgagatgg cacgcgaaaa tcaaacgact cagaaggggc aaaaaaacag tcgagagcgg 2340 atgaagagaa tagaagaggg tattaaagaa ctgggcagcc agatcttaaa ggagcatcct 2400 gtggaaaata cccaattgca gaacgagaaa ctttacctct attacctaca aaatggaagg 2460 gacatgtatg ttgatcagga actggacata aaccgtttat ctgattacga cgtcgatcac 2520 attgtacccc aatccttttt gaaggacgat tcaatcgaca ataaagtgct tacacgctcg 2580 gataagaacc gagggaaaag tgacaatgtt ccaagcgagg aagtcgtaaa gaaaatgaag 2640 aactattggc ggcagctcct aaatgcgaaa ctgataacgc aaagaaagtt cgataactta 2700 actaaagctg agaggggtgg cttgtctgaa cttgacaagg ccggatttat taaacgtcag 2760 ctcgtggaaa cccgccaaat cacaaagcat gttgcacaga tactagattc ccgaatgaat 2820 acgaaatacg acgagaacga taagctgatt cgggaagtca aagtaatcac tttaaagtca 2880 aaattggtgt cggacttcag aaaggatttt caattctata aagttaggga gataaataac 2940 taccaccatg cgcacgacgc ttatcttaat gccgtcgtag ggaccgcact cattaagaaa 3000 tacccgaagc tagaaagtga gtttgtgtat ggtgattaca aagtttatga cgtccgtaag 3060 atgatcgcga aaagcgaaca ggagataggc aaggctacag ccaaatactt cttttattct 3120 aacattatga atttctttaa gacggaaatc actctggcaa acggagagat acgcaaacga 3180 cctttaattg aaaccaatgg ggagacaggt gaaatcgtat gggataaggg ccgggacttc 3240 gcgacggtga gaaaagtttt gtccatgccc caagtcaaca tagtaaagaa aactgaggtg 3300 cagaccggag ggttttcaaa ggaatcgatt cttccaaaaa ggaatagtga taagctcatc 3360 gctcgtaaaa aggactggga cccgaaaaag tacggtggct tcgatagccc tacagttgcc 3420 tattctgtcc tagtagtggc aaaagttgag aagggaaaat ccaagaaact gaagtcagtc 3480 aaagaattat tggggataac gattatggag cgctcgtctt ttgaaaagaa ccccatcgac 3540 ttccttgagg cgaaaggtta caaggaagta aaaaaggatc tcataattaa actaccaaag 3600 tatagtctgt ttgagttaga aaatggccga aaacggatgt tggctagcgc cggagagctt 3660 caaaagggga acgaactcgc actaccgtct aaatacgtga atttcctgta tttagcgtcc 3720 cattacgaga agttgaaagg ttcacctgaa gataacgaac agaagcaact ttttgttgag 3780 cagcacaaac attatctcga cgaaatcata gagcaaattt cggaattcag taagagagtc 3840 atcctagctg atgccaatct ggacaaagta ttaagcgcat acaacaagca cagggataaa 3900 cccatacgtg agcaggcgga aaatattatc catttgttta ctcttaccaa cctcggcgct 3960 ccagccgcat tcaagtattt tgacacaacg atagatcgca aacgatacac ttctaccaag 4020 gaggtgctag acgcgacact gattcaccaa tccatcacgg gattatatga aactcggata 4080 gatttgtcac agcttggggg tgacggatcc cccaagaaga agaggaaagt ctcgagcgac 4140 tacaaagacc atgacggtga ttataaagat catgacatcg attacaagga tgacgatgac 4200 aagtga 4206 <210> 12 <211> 4206 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 12 atggataaaa agtattctat tggtttagac atcggcacta attccgttgg atgggctgtc 60 ataaccgatg aatacaaagt accttcaaag aaatttaagg tgttggggaa cacagaccgt 120 cattcgatta aaaagaatct tatcggtgcc ctcctattcg atagtggcga aacggcagag 180 gcgactcgcc tgaaacgaac cgctcggaga aggtatacac gtcgcaagaa ccgaatatgt 240 tacttacaag aaatttttag caatgagatg gccaaagttg acgattcttt ctttcaccgt 300 ttggaagagt ccttccttgt cgaagaggac aagaaacatg aacggcaccc catctttgga 360 aacatagtag atgaggtggc atatcatgaa aagtacccaa cgatttatca cctcagaaaa 420 aagctagttg actcaactga taaagcggac ctgaggttaa tctacttggc tcttgcccat 480 atgataaagt tccgtgggca ctttctcatt gagggtgatc taaatccgga caactcggat 540 gtcgacaaac tgttcatcca gttagtacaa acctataatc agttgtttga agagaaccct 600 ataaatgcaa gtggcgtgga tgcgaaggct attcttagcg cccgcctctc taaatcccga 660 cggctagaaa acctgatcgc acaattaccc ggagagaaga aaaatgggtt gttcggtaac 720 cttatagcgc tctcactagg cctgacacca aattttaagt cgaacttcga cttagctgaa 780 gatgccaaat tgcagcttag taaggacacg tacgatgacg atctcgacaa tctactggca 840 caaattggag atcagtatgc ggacttattt ttggctgcca aaaaccttag cgatgcaatc 900 ctcctatctg acatactgag agttaatact gagattacca aggcgccgtt atccgcttca 960 atgatcaaaa ggtacgatga acatcaccaa gacttgacac ttctcaaggc cctagtccgt 1020 cagcaactgc ctgagaaata taaggaaata ttctttgatc agtcgaaaaa cgggtacgca 1080 ggttatattg acggcggagc gagtcaagag gaattctaca agtttatcaa acccatatta 1140 gagaagatgg atgggacgga agagttgctt gtaaaactca atcgcgaaga tctactgcga 1200 aagcagcgga ctttcgacaa cggtagcatt ccacatcaaa tccacttagg cgaattgcat 1260 gctatactta gaaggcagga ggatttttat ccgttcctca aagacaatcg tgaaaagatt 1320 gagaaaatcc taacctttcg cataccttac tatgtgggac ccctggcccg agggaactct 1380 cggttcgcat ggatgacaag aaagtccgaa gaaacgatta ctccctggaa ttttgaggaa 1440 gttgtcgata aaggtgcgtc agctcaatcg ttcatcgaga ggatgaccaa ctttgacaag 1500 aatttaccga acgaaaaagt attgcctaag cacagtttac tttacgagta tttcacagtg 1560 tacaatgaac tcacgaaagt taagtatgtc actgagggca tgcgtaaacc cgcctttcta 1620 agcggagaac agaagaaagc aatagtagat ctgttattca agaccaaccg caaagtgaca 1680 gttaagcaat tgaaagagga ctactttaag aaaattgaat gcttcgattc tgtcgagatc 1740 tccggggtag aagatcgatt taatgcgtca cttggtacgt atcatgacct cctaaagata 1800 attaaagata aggacttcct ggataacgaa gagaatgaag atatcttaga agatatagtg 1860 ttgactctta ccctctttga agatcgggaa atgattgagg aaagactaaa aacatacgct 1920 cacctgttcg acgataaggt tatgaaacag ttaaagaggc gtcgctatac gggctgggga 1980 cgattgtcgc ggaaacttat caacgggata agagacaagc aaagtggtaa aactattctc 2040 gattttctaa agagcgacgg cttcgccaat aggaacttta tgcagctgat ccatgatgac 2100 tctttaacct tcaaagagga tatacaaaag gcacaggttt ccggacaagg ggactcattg 2160 cacgaacata ttgcgaatct tgctggttcg ccagccatca aaaagggcat actccagaca 2220 gtcaaagtag tggatgagct agttaaggtc atgggacgtc acaaaccgga aaacattgta 2280 atcgagatgg cacgcgaaaa tcaaacgact cagaaggggc aaaaaaacag tcgagagcgg 2340 atgaagagaa tagaagaggg tattaaagaa ctgggcagcc agatcttaaa ggagcatcct 2400 gtggaaaata cccaattgca gaacgagaaa ctttacctct attacctaca aaatggaagg 2460 gacatgtatg ttgatcagga actggacata aaccgtttat ctgattacga cgtcgatcac 2520 attgtacccc aatccttttt gaaggacgat tcaatcgaca ataaagtgct tacacgctcg 2580 gataagaacc gagggaaaag tgacaatgtt ccaagcgagg aagtcgtaaa gaaaatgaag 2640 aactattggc ggcagctcct aaatgcgaaa ctgataacgc aaagaaagtt cgataactta 2700 actaaagctg agaggggtgg cttgtctgaa cttgacaagg ccggatttat taaacgtcag 2760 ctcgtggaaa cccgccaaat cacaaagcat gttgcacaga tactagattc ccgaatgaat 2820 acgaaatacg acgagaacga taagctgatt cgggaagtca aagtaatcac tttaaagtca 2880 aaattggtgt cggacttcag aaaggatttt caattctata aagttaggga gataaataac 2940 taccaccatg cgcacgacgc ttatcttaat gccgtcgtag ggaccgcact cattaagaaa 3000 tacccgaagc tagaaagtga gtttgtgtat ggtgattaca aagtttatga cgtccgtaag 3060 atgatcgcga aaagcgaaca ggagataggc aaggctacag ccaaatactt cttttattct 3120 aacattatga atttctttaa gacggaaatc actctggcaa acggagagat acgcaaacga 3180 cctttaattg aaaccaatgg ggagacaggt gaaatcgtat gggataaggg ccgggacttc 3240 gcgacggtga gaaaagtttt gtccatgccc caagtcaaca tagtaaagaa aactgaggtg 3300 cagaccggag ggttttcaaa ggaatcgatt cttccaaaaa ggaatagtga taagctcatc 3360 gctcgtaaaa aggactggga cccgaaaaag tacggtggct tcgtgagccc tacagttgcc 3420 tattctgtcc tagtagtggc aaaagttgag aagggaaaat ccaagaaact gaagtcagtc 3480 aaagaattat tggggataac gattatggag cgctcgtctt ttgaaaagaa ccccatcgac 3540 ttccttgagg cgaaaggtta caaggaagta aaaaaggatc tcataattaa actaccaaag 3600 tatagtctgt ttgagttaga aaatggccga aaacggatgt tggctagcgc cggagagctt 3660 caaaagggga acgaactcgc actaccgtct aaatacgtga atttcctgta tttagcgtcc 3720 cattacgaga agttgaaagg ttcacctgaa gataacgaac agaagcaact ttttgttgag 3780 cagcacaaac attatctcga cgaaatcata gagcaaattt cggaattcag taagagagtc 3840 atcctagctg atgccaatct ggacaaagta ttaagcgcat acaacaagca cagggataaa 3900 cccatacgtg agcaggcgga aaatattatc catttgttta ctcttaccaa cctcggcgct 3960 ccagccgcat tcaagtattt tgacacaacg atagatcgca aacagtacag atctaccaag 4020 gaggtgctag acgcgacact gattcaccaa tccatcacgg gattatatga aactcggata 4080 gatttgtcac agcttggggg tgacggatcc cccaagaaga agaggaaagt ctcgagcgac 4140 tacaaagacc atgacggtga ttataaagat catgacatcg attacaagga tgacgatgac 4200 aagtga 4206 <210> 13 <211> 4206 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 13 atggataaaa agtattctat tggtttagac atcggcacta attccgttgg atgggctgtc 60 ataaccgatg aatacaaagt accttcaaag aaatttaagg tgttggggaa cacagaccgt 120 cattcgatta aaaagaatct tatcggtgcc ctcctattcg atagtggcga aacggcagag 180 gcgactcgcc tgaaacgaac cgctcggaga aggtatacac gtcgcaagaa ccgaatatgt 240 tacttacaag aaatttttag caatgagatg gccaaagttg acgattcttt ctttcaccgt 300 ttggaagagt ccttccttgt cgaagaggac aagaaacatg aacggcaccc catctttgga 360 aacatagtag atgaggtggc atatcatgaa aagtacccaa cgatttatca cctcagaaaa 420 aagctagttg actcaactga taaagcggac ctgaggttaa tctacttggc tcttgcccat 480 atgataaagt tccgtgggca ctttctcatt gagggtgatc taaatccgga caactcggat 540 gtcgacaaac tgttcatcca gttagtacaa acctataatc agttgtttga agagaaccct 600 ataaatgcaa gtggcgtgga tgcgaaggct attcttagcg cccgcctctc taaatcccga 660 cggctagaaa acctgatcgc acaattaccc ggagagaaga aaaatgggtt gttcggtaac 720 cttatagcgc tctcactagg cctgacacca aattttaagt cgaacttcga cttagctgaa 780 gatgccaaat tgcagcttag taaggacacg tacgatgacg atctcgacaa tctactggca 840 caaattggag atcagtatgc ggacttattt ttggctgcca aaaaccttag cgatgcaatc 900 ctcctatctg acatactgag agttaatact gagattacca aggcgccgtt atccgcttca 960 atgatcaaaa ggtacgatga acatcaccaa gacttgacac ttctcaaggc cctagtccgt 1020 cagcaactgc ctgagaaata taaggaaata ttctttgatc agtcgaaaaa cgggtacgca 1080 ggttatattg acggcggagc gagtcaagag gaattctaca agtttatcaa acccatatta 1140 gagaagatgg atgggacgga agagttgctt gtaaaactca atcgcgaaga tctactgcga 1200 aagcagcgga ctttcgacaa cggtagcatt ccacatcaaa tccacttagg cgaattgcat 1260 gctatactta gaaggcagga ggatttttat ccgttcctca aagacaatcg tgaaaagatt 1320 gagaaaatcc taacctttcg cataccttac tatgtgggac ccctggcccg agggaactct 1380 cggttcgcat ggatgacaag aaagtccgaa gaaacgatta ctccctggaa ttttgaggaa 1440 gttgtcgata aaggtgcgtc agctcaatcg ttcatcgaga ggatgaccaa ctttgacaag 1500 aatttaccga acgaaaaagt attgcctaag cacagtttac tttacgagta tttcacagtg 1560 tacaatgaac tcacgaaagt taagtatgtc actgagggca tgcgtaaacc cgcctttcta 1620 agcggagaac agaagaaagc aatagtagat ctgttattca agaccaaccg caaagtgaca 1680 gttaagcaat tgaaagagga ctactttaag aaaattgaat gcttcgattc tgtcgagatc 1740 tccggggtag aagatcgatt taatgcgtca cttggtacgt atcatgacct cctaaagata 1800 attaaagata aggacttcct ggataacgaa gagaatgaag atatcttaga agatatagtg 1860 ttgactctta ccctctttga agatcgggaa atgattgagg aaagactaaa aacatacgct 1920 cacctgttcg acgataaggt tatgaaacag ttaaagaggc gtcgctatac gggctgggga 1980 cgattgtcgc ggaaacttat caacgggata agagacaagc aaagtggtaa aactattctc 2040 gattttctaa agagcgacgg cttcgccaat aggaacttta tgcagctgat ccatgatgac 2100 tctttaacct tcaaagagga tatacaaaag gcacaggttt ccggacaagg ggactcattg 2160 cacgaacata ttgcgaatct tgctggttcg ccagccatca aaaagggcat actccagaca 2220 gtcaaagtag tggatgagct agttaaggtc atgggacgtc acaaaccgga aaacattgta 2280 atcgagatgg cacgcgaaaa tcaaacgact cagaaggggc aaaaaaacag tcgagagcgg 2340 atgaagagaa tagaagaggg tattaaagaa ctgggcagcc agatcttaaa ggagcatcct 2400 gtggaaaata cccaattgca gaacgagaaa ctttacctct attacctaca aaatggaagg 2460 gacatgtatg ttgatcagga actggacata aaccgtttat ctgattacga cgtcgatcac 2520 attgtacccc aatccttttt gaaggacgat tcaatcgaca ataaagtgct tacacgctcg 2580 gataagaacc gagggaaaag tgacaatgtt ccaagcgagg aagtcgtaaa gaaaatgaag 2640 aactattggc ggcagctcct aaatgcgaaa ctgataacgc aaagaaagtt cgataactta 2700 actaaagctg agaggggtgg cttgtctgaa cttgacaagg ccggatttat taaacgtcag 2760 ctcgtggaaa cccgccaaat cacaaagcat gttgcacaga tactagattc ccgaatgaat 2820 acgaaatacg acgagaacga taagctgatt cgggaagtca aagtaatcac tttaaagtca 2880 aaattggtgt cggacttcag aaaggatttt caattctata aagttaggga gataaataac 2940 taccaccatg cgcacgacgc ttatcttaat gccgtcgtag ggaccgcact cattaagaaa 3000 tacccgaagc tagaaagtga gtttgtgtat ggtgattaca aagtttatga cgtccgtaag 3060 atgatcgcga aaagcgaaca ggagataggc aaggctacag ccaaatactt cttttattct 3120 aacattatga atttctttaa gacggaaatc actctggcaa acggagagat acgcaaacga 3180 cctttaattg aaaccaatgg ggagacaggt gaaatcgtat gggataaggg ccgggacttc 3240 gcgacggtga gaaaagtttt gtccatgccc caagtcaaca tagtaaagaa aactgaggtg 3300 cagaccggag ggttttcaaa ggaatcgatt cttccaaaaa ggaatagtga taagctcatc 3360 gctcgtaaaa aggactggga cccgaaaaag tacggtggct tcgagagccc tacagttgcc 3420 tattctgtcc tagtagtggc aaaagttgag aagggaaaat ccaagaaact gaagtcagtc 3480 aaagaattat tggggataac gattatggag cgctcgtctt ttgaaaagaa ccccatcgac 3540 ttccttgagg cgaaaggtta caaggaagta aaaaaggatc tcataattaa actaccaaag 3600 tatagtctgt ttgagttaga aaatggccga aaacggatgt tggctagcgc cggagagctt 3660 caaaagggga acgaactcgc actaccgtct aaatacgtga atttcctgta tttagcgtcc 3720 cattacgaga agttgaaagg ttcacctgaa gataacgaac agaagcaact ttttgttgag 3780 cagcacaaac attatctcga cgaaatcata gagcaaattt cggaattcag taagagagtc 3840 atcctagctg atgccaatct ggacaaagta ttaagcgcat acaacaagca cagggataaa 3900 cccatacgtg agcaggcgga aaatattatc catttgttta ctcttaccaa cctcggcgct 3960 ccagccgcat tcaagtattt tgacacaacg atagatcgca aacagtacag atctaccaag 4020 gaggtgctag acgcgacact gattcaccaa tccatcacgg gattatatga aactcggata 4080 gatttgtcac agcttggggg tgacggatcc cccaagaaga agaggaaagt ctcgagcgac 4140 tacaaagacc atgacggtga ttataaagat catgacatcg attacaagga tgacgatgac 4200 aagtga 4206 <210> 14 <211> 4206 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 14 atggataaaa agtattctat tggtttagac atcggcacta attccgttgg atgggctgtc 60 ataaccgatg aatacaaagt accttcaaag aaatttaagg tgttggggaa cacagaccgt 120 cattcgatta aaaagaatct tatcggtgcc ctcctattcg atagtggcga aacggcagag 180 gcgactcgcc tgaaacgaac cgctcggaga aggtatacac gtcgcaagaa ccgaatatgt 240 tacttacaag aaatttttag caatgagatg gccaaagttg acgattcttt ctttcaccgt 300 ttggaagagt ccttccttgt cgaagaggac aagaaacatg aacggcaccc catctttgga 360 aacatagtag atgaggtggc atatcatgaa aagtacccaa cgatttatca cctcagaaaa 420 aagctagttg actcaactga taaagcggac ctgaggttaa tctacttggc tcttgcccat 480 atgataaagt tccgtgggca ctttctcatt gagggtgatc taaatccgga caactcggat 540 gtcgacaaac tgttcatcca gttagtacaa acctataatc agttgtttga agagaaccct 600 ataaatgcaa gtggcgtgga tgcgaaggct attcttagcg cccgcctctc taaatcccga 660 cggctagaaa acctgatcgc acaattaccc ggagagaaga aaaatgggtt gttcggtaac 720 cttatagcgc tctcactagg cctgacacca aattttaagt cgaacttcga cttagctgaa 780 gatgccaaat tgcagcttag taaggacacg tacgatgacg atctcgacaa tctactggca 840 caaattggag atcagtatgc ggacttattt ttggctgcca aaaaccttag cgatgcaatc 900 ctcctatctg acatactgag agttaatact gagattacca aggcgccgtt atccgcttca 960 atgatcaaaa ggtacgatga acatcaccaa gacttgacac ttctcaaggc cctagtccgt 1020 cagcaactgc ctgagaaata taaggaaata ttctttgatc agtcgaaaaa cgggtacgca 1080 ggttatattg acggcggagc gagtcaagag gaattctaca agtttatcaa acccatatta 1140 gagaagatgg atgggacgga agagttgctt gtaaaactca atcgcgaaga tctactgcga 1200 aagcagcgga ctttcgacaa cggtagcatt ccacatcaaa tccacttagg cgaattgcat 1260 gctatactta gaaggcagga ggatttttat ccgttcctca aagacaatcg tgaaaagatt 1320 gagaaaatcc taacctttcg cataccttac tatgtgggac ccctggcccg agggaactct 1380 cggttcgcat ggatgacaag aaagtccgaa gaaacgatta ctccctggaa ttttgaggaa 1440 gttgtcgata aaggtgcgtc agctcaatcg ttcatcgaga ggatgaccaa ctttgacaag 1500 aatttaccga acgaaaaagt attgcctaag cacagtttac tttacgagta tttcacagtg 1560 tacaatgaac tcacgaaagt taagtatgtc actgagggca tgcgtaaacc cgcctttcta 1620 agcggagaac agaagaaagc aatagtagat ctgttattca agaccaaccg caaagtgaca 1680 gttaagcaat tgaaagagga ctactttaag aaaattgaat gcttcgattc tgtcgagatc 1740 tccggggtag aagatcgatt taatgcgtca cttggtacgt atcatgacct cctaaagata 1800 attaaagata aggacttcct ggataacgaa gagaatgaag atatcttaga agatatagtg 1860 ttgactctta ccctctttga agatcgggaa atgattgagg aaagactaaa aacatacgct 1920 cacctgttcg acgataaggt tatgaaacag ttaaagaggc gtcgctatac gggctgggga 1980 cgattgtcgc ggaaacttat caacgggata agagacaagc aaagtggtaa aactattctc 2040 gattttctaa agagcgacgg cttcgccaat aggaacttta tgcagctgat ccatgatgac 2100 tctttaacct tcaaagagga tatacaaaag gcacaggttt ccggacaagg ggactcattg 2160 cacgaacata ttgcgaatct tgctggttcg ccagccatca aaaagggcat actccagaca 2220 gtcaaagtag tggatgagct agttaaggtc atgggacgtc acaaaccgga aaacattgta 2280 atcgagatgg cacgcgaaaa tcaaacgact cagaaggggc aaaaaaacag tcgagagcgg 2340 atgaagagaa tagaagaggg tattaaagaa ctgggcagcc agatcttaaa ggagcatcct 2400 gtggaaaata cccaattgca gaacgagaaa ctttacctct attacctaca aaatggaagg 2460 gacatgtatg ttgatcagga actggacata aaccgtttat ctgattacga cgtcgatcac 2520 attgtacccc aatccttttt gaaggacgat tcaatcgaca ataaagtgct tacacgctcg 2580 gataagaacc gagggaaaag tgacaatgtt ccaagcgagg aagtcgtaaa gaaaatgaag 2640 aactattggc ggcagctcct aaatgcgaaa ctgataacgc aaagaaagtt cgataactta 2700 actaaagctg agaggggtgg cttgtctgaa cttgacaagg ccggatttat taaacgtcag 2760 ctcgtggaaa cccgccaaat cacaaagcat gttgcacaga tactagattc ccgaatgaat 2820 acgaaatacg acgagaacga taagctgatt cgggaagtca aagtaatcac tttaaagtca 2880 aaattggtgt cggacttcag aaaggatttt caattctata aagttaggga gataaataac 2940 taccaccatg cgcacgacgc ttatcttaat gccgtcgtag ggaccgcact cattaagaaa 3000 tacccgaagc tagaaagtga gtttgtgtat ggtgattaca aagtttatga cgtccgtaag 3060 atgatcgcga aaagcgaaca ggagataggc aaggctacag ccaaatactt cttttattct 3120 aacattatga atttctttaa gacggaaatc actctggcaa acggagagat acgcaaacga 3180 cctttaattg aaaccaatgg ggagacaggt gaaatcgtat gggataaggg ccgggacttc 3240 gcgacggtga gaaaagtttt gtccatgccc caagtcaaca tagtaaagaa aactgaggtg 3300 cagaccggag ggttttcaaa ggaatcgatt cttccaaaaa ggaatagtga taagctcatc 3360 gctcgtaaaa aggactggga cccgaaaaag tacggtggct tcgtgagccc tacagttgcc 3420 tattctgtcc tagtagtggc aaaagttgag aagggaaaat ccaagaaact gaagtcagtc 3480 aaagaattat tggggataac gattatggag cgctcgtctt ttgaaaagaa ccccatcgac 3540 ttccttgagg cgaaaggtta caaggaagta aaaaaggatc tcataattaa actaccaaag 3600 tatagtctgt ttgagttaga aaatggccga aaacggatgt tggctagcgc cagagagctt 3660 caaaagggga acgaactcgc actaccgtct aaatacgtga atttcctgta tttagcgtcc 3720 cattacgaga agttgaaagg ttcacctgaa gataacgaac agaagcaact ttttgttgag 3780 cagcacaaac attatctcga cgaaatcata gagcaaattt cggaattcag taagagagtc 3840 atcctagctg atgccaatct ggacaaagta ttaagcgcat acaacaagca cagggataaa 3900 cccatacgtg agcaggcgga aaatattatc catttgttta ctcttaccaa cctcggcgct 3960 ccagccgcat tcaagtattt tgacacaacg atagatcgca aagagtacag atctaccaag 4020 gaggtgctag acgcgacact gattcaccaa tccatcacgg gattatatga aactcggata 4080 gatttgtcac agcttggggg tgacggatcc cccaagaaga agaggaaagt ctcgagcgac 4140 tacaaagacc atgacggtga ttataaagat catgacatcg attacaagga tgacgatgac 4200 aagtga 4206 <210> 15 <211> 4206 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 15 atggataaaa agtattctat tggtttagac atcggcacta attccgttgg atgggctgtc 60 ataaccgatg aatacaaagt accttcaaag aaatttaagg tgttggggaa cacagaccgt 120 cattcgatta aaaagaatct tatcggtgcc ctcctattcg atagtggcga aacggcagag 180 gcgactcgcc tgaaacgaac cgctcggaga aggtatacac gtcgcaagaa ccgaatatgt 240 tacttacaag aaatttttag caatgagatg gccaaagttg acgattcttt ctttcaccgt 300 ttggaagagt ccttccttgt cgaagaggac aagaaacatg aacggcaccc catctttgga 360 aacatagtag atgaggtggc atatcatgaa aagtacccaa cgatttatca cctcagaaaa 420 aagctagttg actcaactga taaagcggac ctgaggttaa tctacttggc tcttgcccat 480 atgataaagt tccgtgggca ctttctcatt gagggtgatc taaatccgga caactcggat 540 gtcgacaaac tgttcatcca gttagtacaa acctataatc agttgtttga agagaaccct 600 ataaatgcaa gtggcgtgga tgcgaaggct attcttagcg cccgcctctc taaatcccga 660 cggctagaaa acctgatcgc acaattaccc ggagagaaga aaaatgggtt gttcggtaac 720 cttatagcgc tctcactagg cctgacacca aattttaagt cgaacttcga cttagctgaa 780 gatgccaaat tgcagcttag taaggacacg tacgatgacg atctcgacaa tctactggca 840 caaattggag atcagtatgc ggacttattt ttggctgcca aaaaccttag cgatgcaatc 900 ctcctatctg acatactgag agttaatact gagattacca aggcgccgtt atccgcttca 960 atgatcaaaa ggtacgatga acatcaccaa gacttgacac ttctcaaggc cctagtccgt 1020 cagcaactgc ctgagaaata taaggaaata ttctttgatc agtcgaaaaa cgggtacgca 1080 ggttatattg acggcggagc gagtcaagag gaattctaca agtttatcaa acccatatta 1140 gagaagatgg atgggacgga agagttgctt gtaaaactca atcgcgaaga tctactgcga 1200 aagcagcgga ctttcgacaa cggtagcatt ccacatcaaa tccacttagg cgaattgcat 1260 gctatactta gaaggcagga ggatttttat ccgttcctca aagacaatcg tgaaaagatt 1320 gagaaaatcc taacctttcg cataccttac tatgtgggac ccctggcccg agggaactct 1380 cggttcgcat ggatgacaag aaagtccgaa gaaacgatta ctccctggaa ttttgaggaa 1440 gttgtcgata aaggtgcgtc agctcaatcg ttcatcgaga ggatgaccaa ctttgacaag 1500 aatttaccga acgaaaaagt attgcctaag cacagtttac tttacgagta tttcacagtg 1560 tacaatgaac tcacgaaagt taagtatgtc actgagggca tgcgtaaacc cgcctttcta 1620 agcggagaac agaagaaagc aatagtagat ctgttattca agaccaaccg caaagtgaca 1680 gttaagcaat tgaaagagga ctactttaag aaaattgaat gcttcgattc tgtcgagatc 1740 tccggggtag aagatcgatt taatgcgtca cttggtacgt atcatgacct cctaaagata 1800 attaaagata aggacttcct ggataacgaa gagaatgaag atatcttaga agatatagtg 1860 ttgactctta ccctctttga agatcgggaa atgattgagg aaagactaaa aacatacgct 1920 cacctgttcg acgataaggt tatgaaacag ttaaagaggc gtcgctatac gggctgggga 1980 cgattgtcgc ggaaacttat caacgggata agagacaagc aaagtggtaa aactattctc 2040 gattttctaa agagcgacgg cttcgccaat aggaacttta tgcagctgat ccatgatgac 2100 tctttaacct tcaaagagga tatacaaaag gcacaggttt ccggacaagg ggactcattg 2160 cacgaacata ttgcgaatct tgctggttcg ccagccatca aaaagggcat actccagaca 2220 gtcaaagtag tggatgagct agttaaggtc atgggacgtc acaaaccgga aaacattgta 2280 atcgagatgg cacgcgaaaa tcaaacgact cagaaggggc aaaaaaacag tcgagagcgg 2340 atgaagagaa tagaagaggg tattaaagaa ctgggcagcc agatcttaaa ggagcatcct 2400 gtggaaaata cccaattgca gaacgagaaa ctttacctct attacctaca aaatggaagg 2460 gacatgtatg ttgatcagga actggacata aaccgtttat ctgattacga cgtcgatcac 2520 attgtacccc aatccttttt gaaggacgat tcaatcgaca ataaagtgct tacacgctcg 2580 gataagaacc gagggaaaag tgacaatgtt ccaagcgagg aagtcgtaaa gaaaatgaag 2640 aactattggc ggcagctcct aaatgcgaaa ctgataacgc aaagaaagtt cgataactta 2700 actaaagctg agaggggtgg cttgtctgaa cttgacaagg ccggatttat taaacgtcag 2760 ctcgtggaaa cccgccaaat cacaaagcat gttgcacaga tactagattc ccgaatgaat 2820 acgaaatacg acgagaacga taagctgatt cgggaagtca aagtaatcac tttaaagtca 2880 aaattggtgt cggacttcag aaaggatttt caattctata aagttaggga gataaataac 2940 taccaccatg cgcacgacgc ttatcttaat gccgtcgtag ggaccgcact cattaagaaa 3000 tacccgaagc tagaaagtga gtttgtgtat ggtgattaca aagtttatga cgtccgtaag 3060 atgatcgcga aaagcgaaca ggagataggc aaggctacag ccaaatactt cttttattct 3120 aacattatga atttctttaa gacggaaatc actctggcaa acggagagat acgcaaacga 3180 cctttaattg aaaccaatgg ggagacaggt gaaatcgtat gggataaggg ccgggacttc 3240 gcgacggtga gaaaagtttt gtccatgccc caagtcaaca tagtaaagaa aactgaggtg 3300 cagaccggag ggttttcaaa ggaatcgatt cttccaaaaa ggaatagtga taagctcatc 3360 gctcgtaaaa aggactggga cccgaaaaag tacggtggct tcgagagccc tacagttgcc 3420 tattctgtcc tagtagtggc aaaagttgag aagggaaaat ccaagaaact gaagtcagtc 3480 aaagaattat tggggataac gattatggag cgctcgtctt ttgaaaagaa ccccatcgac 3540 ttccttgagg cgaaaggtta caaggaagta aaaaaggatc tcataattaa actaccaaag 3600 tatagtctgt ttgagttaga aaatggccga aaacggatgt tggctagcgc cggagagctt 3660 caaaagggga acgaactcgc actaccgtct aaatacgtga atttcctgta tttagcgtcc 3720 cattacgaga agttgaaagg ttcacctgaa gataacgaac agaagcaact ttttgttgag 3780 cagcacaaac attatctcga cgaaatcata gagcaaattt cggaattcag taagagagtc 3840 atcctagctg atgccaatct ggacaaagta ttaagcgcat acaacaagca cagggataaa 3900 cccatacgtg agcaggcgga aaatattatc catttgttta ctcttaccaa cctcggcgct 3960 ccagccgcat tcaagtattt tgacacaacg atagatcgca aacgatacac ttctaccaag 4020 gaggtgctag acgcgacact gattcaccaa tccatcacgg gattatatga aactcggata 4080 gatttgtcac agcttggggg tgacggatcc cccaagaaga agaggaaagt ctcgagcgac 4140 tacaaagacc atgacggtga ttataaagat catgacatcg attacaagga tgacgatgac 4200 aagtga 4206 <210> 16 <211> 3402 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 16 atgggcagcg acctggtgct gggcctggac atcggcatcg gcagcgtggg cgtgggcatc 60 ctgaacaagg tgaccggcga gatcatccac aagaacagtc gcatcttccc tgctgctcag 120 gctgagaaca acctggtgcg ccgcaccaac cgccagggtc gccggcttgc tcgccgcaag 180 aagcaccggc gcgtgcgcct gaaccgcctg ttcgaggaga gcggcctgat caccgacttc 240 accaagatca gcatcaacct gaacccctac cagctgcgcg tgaagggcct gaccgacgag 300 ctgagcaacg aggagctgtt catcgccctg aagaacatgg tgaagcaccg cggcatcagc 360 tacctggacg acgccagcga cgacggcaac agcagcgtgg gcgactacgc ccagatcgtg 420 aaggagaaca gcaagcagct ggagaccaag acccccggcc agatccagct ggagcgctac 480 cagacctacg gccagctgcg cggcgacttc accgtggaga aggacggcaa gaagcaccgc 540 ctgatcaacg tgttccccac cagcgcctac cgcagcgagg ccctgcgcat cctgcagacc 600 cagcaggagt tcaaccccca gatcaccgac gagttcatca accgctacct ggagatcctg 660 accggcaagc gcaagtacta ccacggcccc ggcaacgaga agagccgcac cgactacggc 720 cgctaccgca ccagcggcga gaccctggac aacatcttcg gcatcctgat cggcaagtgc 780 accttctacc ccgacgagtt ccgcgccgcc aaggccagct acaccgccca ggagttcaat 840 ctgctgaacg acctgaacaa cctgaccgtg cccaccgaga ccaagaagct gagcaaggag 900 cagaagaacc agatcatcaa ctacgtgaag aacgagaagg ctatgggccc cgccaagctg 960 ttcaagtaca tcgccaagct gctgagctgc gacgtggccg acatcaaggg ctaccgcatc 1020 gacaagagcg gcaaggccga gatccacacc ttcgaggcct accgcaagat gaagaccctg 1080 gagaccctgg acatcgagca gatggaccga gagaccctgg acaagctggc ctacgtgctg 1140 accctgaaca ccgagcgcga gggcatccag gaggccctgg agcacgagtt cgccgacggc 1200 agcttcagcc agaaacaggt ggacgagctg gtgcagttcc gcaaggccaa cagcagcatc 1260 ttcggcaagg gctggcacaa cttcagcgtg aagctgatga tggagctgat ccccgagctg 1320 tacgagacca gcgaggagca gatgaccatc ctgacccgcc tgggcaagca gaagaccacc 1380 agcagcagca acaagaccaa gtacatcgac gagaagctgc tgaccgagga gatctacaac 1440 cccgtggtgg ccaagagcgt gcgccaggcc atcaagatcg tgaacgccgc catcaaggag 1500 tacggcgact tcgacaacat cgtgatcgag atggcccgcg agaccaacga ggacgacgag 1560 aagaaggcca tccagaagat ccagaaggcc aacaaggacg agaaggacgc cgccatgctg 1620 aaggccgcca accagtacaa cggcaaggcc gagctgcccc acagcgtgtt ccacggccac 1680 aagcagctgg ccaccaagat ccgcctgtgg caccagcagg gcgagcgctg cctgtacacc 1740 ggcaagacca tcagcatcca cgacctgatc aacaacagca accagttcga ggtggaccac 1800 atcctgcccc tgagcatcac cttcgacgac agcctggcca acaaggtgct ggtgtacgcc 1860 accgccaacc aggagaaggg ccagcgcacc ccctaccagg ccctggacag catggacgac 1920 gcctggagct tccgcgagct gaaggccttc gtgcgcgaga gcaagaccct gagcaacaag 1980 aagaaggagt atctgctgac cgaggaggac atcagcaagt tcgacgtgcg caagaagttc 2040 atcgagcgca acctggtgga cacccgctac gccagccgcg tggtgctgaa cgccctgcag 2100 gagcacttcc gcgcccacaa gatcgacacc aaggtgagcg tggtgcgcgg ccagttcacc 2160 agccagctgc gccgccactg gggcatcgag aagacccgcg acacctacca ccaccacgcc 2220 gtggacgccc tgatcattgc ggcttctagc cagctgaacc tgtggaagaa gcagaagaac 2280 accctggtga gctacagcga ggaccagctg ctggacatcg agaccggcga gctgatcagc 2340 gacgacgagt acaaggagag cgtgttcaag gccccctacc agcacttcgt ggacaccctg 2400 aagagcaagg agttcgagga cagcatcctg ttcagctacc aggtggacag caagttcaac 2460 cgcaagatca gcgacgccac catctacgcc acccgccagg ccaaggtggg caaggacaag 2520 gccgacgaga cctacgtgct gggcaagatc aaggacatct acacccagga cggctacgac 2580 gccttcatga agatctacaa gaaggacaag agcaagttcc tgatgtaccg ccacgacccc 2640 cagaccttcg agaaggtgat cgagcccatc ctggagaact accccaacaa gcagatcaac 2700 gataaaggca aggaggtgcc ctgcaacccc ttcctgaagt acaaggagga gcacggctac 2760 atccgcaagt acagcaagaa gggcaacggc cccgagatca agagcctgaa gtactacgac 2820 agcaagctgg gcaaccacat cgacatcacc cccaaggaca gcaacaacaa ggtggtgctg 2880 cagagcgtga gcccctggcg cgccgacgtg tacttcaaca agaccaccgg caagtacgag 2940 atcctggggc tgaagtacgc cgatctgcag tttgataaag gcacaggcac ctacaagatc 3000 agccaggaga agtacaacga catcaagaag aaggagggcg tggacagcga cagcgagttc 3060 aagttcaccc tgtacaagaa cgaccttctg ctggtgaagg acaccgagac caaggagcaa 3120 cagctgttcc gcttcctgag ccgcaccatg cccaagcaga agcactacgt ggagctgaag 3180 ccctacgaca agcagaagtt cgagggcggc gaggccctga tcaaggtgct gggcaacgtg 3240 gccaacagcg gccagtgcaa gaagggcctg ggcaagagca acatcagcat ctacaaggtg 3300 cgcaccgacg tgctgggcaa ccagcacatc atcaagaacg agggcgacaa gcccaagttg 3360 gacttcagca gggctgaccc caagaagaag aggaaggtgt ga 3402 <210> 17 <211> 3264 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 17 atggggaaac ggaactacat cctggggctt gacattggga taaccagcgt tggctacgga 60 attattgatt atgagacacg cgatgtgatt gacgccgggg ttaggctgtt caaagaggcc 120 aacgttgaaa acaacgaggg aagacggagt aagcgcggag caagaagact caagcgcaga 180 cggagacatc ggattcagag ggtgaaaaag ctgctcttcg attacaatct cctgaccgat 240 catagtgagc tgagcggaat caacccctac gaggcgcgag tgaaagggct ttcccagaag 300 ctgtccgaag aggagttctc cgccgcgttg ctgcacctgg ccaaacggag gggggttcac 360 aatgtaaacg aagtggagga ggacacgggc aatgaactta gtacgaaaga acagatcagt 420 aggaactcta aggctctcga agagaaatac gtcgctgagt tgcagcttga gagactgaaa 480 aaagacggcg aagtacgcgg atctattaat aggttcaaga cttcagatta cgtaaaggaa 540 gccaagcagc tcctgaaagt acagaaagcg taccatcagc tcgatcagag cttcatcgat 600 acctacatag atttgctgga gacacggagg acatactacg agggcccagg ggaaggatct 660 ccttttgggt ggaaggacat caaggaatgg tacgagatgc ttatgggaca ttgtacatat 720 tttccggagg agctcaggag cgtcaagtac gcctacaatg ccgacctgta caatgccctc 780 aatgacctca ataacctcgt gattaccagg gacgagaacg agaagctgga gtactatgaa 840 aagttccaga ttatcgagaa tgtgtttaag cagaagaaga agccgacact taagcagatt 900 gcaaaggaaa tcctcgtgaa tgaggaagat atcaagggat acagagtgac aagtacaggc 960 aagcccgagt tcacaaatct gaaggtgtac cacgatatta aggacataac cgcacgaaag 1020 gagataatcg aaaacgctga gctcctcgat cagatcgcaa aaattcttac catctaccag 1080 tctagtgagg acattcagga ggaactgact aatctgaaca gtgagctcac ccaagaggaa 1140 attgagcaga tttcaaacct gaaaggctac accgggacgc acaatctgag cctcaaagca 1200 atcaacctca ttctggatga actttggcac acaaatgaca accaaattgc catattcaac 1260 cgcctgaaac tggtgccaaa aaaagtggat ctgtcacagc aaaaggaaat ccctacaacc 1320 ttggttgacg attttattct gtcccccgtt gtcaagcgga gcttcatcca gtcaatcaag 1380 gtgatcaatg ccatcattaa aaaatacgga ttgccaaacg atataattat cgagcttgca 1440 cgagagaaga actcaaagga cgcccagaag atgattaacg aaatgcagaa gcgcaaccgc 1500 cagacaaacg aacgcataga ggaaattata agaacaaccg gcaaagagaa tgccaagtat 1560 ctgatcgaga aaatcaagct gcacgacatg caagaaggca agtgcctgta ctctctggaa 1620 gctatcccac tcgaagatct gctgaataat ccattcaatt acgaggtgga ccacatcatc 1680 cctagatccg taagctttga caattccttc aataacaaag ttctggttaa acaggaggaa 1740 aattctaaaa aagggaaccg gaccccgttc cagtacctga gctccagtga cagcaagatt 1800 agctacgaga cttttaagaa acatattctg aatctggcca aaggcaaagg caggatcagc 1860 aagaccaaga aggagtacct cctcgaagaa cgcgacatta acagatttag tgtgcagaaa 1920 gatttcatca accgaaacct tgtcgatact cggtacgcca cgagaggcct gatgaatctc 1980 ctcaggagct acttccgcgt caataatctg gacgttaaag tcaagagcat aaatggggga 2040 ttcaccagct ttctgaggag aaagtggaag tttaagaagg aacgaaacaa aggatacaag 2100 caccatgctg aggatgcttt gatcatcgct aacgcggact ttatctttaa ggaatggaaa 2160 aagctggata aggcaaagaa agtgatggaa aaccagatgt tcgaggagaa gcaggcagag 2220 tcaatgcctg agatcgagac agagcaggaa tacaaggaaa ttttcatcac ccctcatcag 2280 attaaacaca taaaggactt caaagactat aaatactctc atagggtgga caaaaaaccc 2340 aatcgcgagc tcattaatga caccctgtac tcaacacgga aggatgataa aggtaatacc 2400 ttgattgtga ataatcttaa tggattgtat gacaaagata acgacaagct caagaagctg 2460 atcaacaagt ctccagagaa gctccttatg tatcaccacg acccacagac ttatcagaaa 2520 ttgaaactga tcatggagca atacggggat gagaagaacc cactctacaa atattatgag 2580 gaaacaggta attacctgac caagtactcc aagaaggata acggaccagt gatcaaaaag 2640 ataaagtact atggcaacaa acttaatgcg catttggaca taactgacga ttaccccaat 2700 tctcgaaaca aggttgtgaa gctctccctg aagccttata gatttgacgt gtacctggat 2760 aatggggttt ataaattcgt caccgtgaaa aatctggacg tgatcaaaaa ggagaactat 2820 tatgaagtaa actcaaagtg ctatgaggag gcgaagaagc tgaagaagat ctccaatcag 2880 gccgagttca tcgcttcctt ctataataac gatctcatca agatcaatgg agagctttat 2940 cgcgtcattg gtgtgaacaa tgacttgctg aacaggatcg aagtcaatat gatagacatt 3000 acctaccggg agtatctcga aaacatgaat gataaacggc cgcctcgcat catcaagaca 3060 atcgcatcta aaactcagtc aataaaaaag tactctaccg atatcctggg gaatctctat 3120 gaagtgaagt caaagaagca cccacaaatc attaaaaaag gtggatcccc caagaagaag 3180 aggaaagtct cgagcgacta caaagaccat gacggtgatt ataaagatca tgacatcgat 3240 tacaaggatg acgatgacaa gtaa 3264 <210> 18 <211> 422 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 18 tgtacaaaaa agcaggcttt aaaggaacca attcagtcga ctggatccgg taccaaggtc 60 gggcaggaag agggcctatt tcccatgatt ccttcatatt tgcatatacg atacaaggct 120 gttagagaga taattagaat taatttgact gtaaacacaa agatattagt acaaaatacg 180 tgacgtagaa agtaataatt tcttgggtag tttgcagttt taaaattatg ttttaaaatg 240 gactatcata tgcttaccgt aacttgaaag tatttcgatt tcttggcttt atatatcttg 300 tggaaaggac gaaacaccgg agacgattaa tgcgtctccg ttttagagct agaaatagca 360 agttaaaata aggctagtcc gttatcaact tgaaaaagtg gcaccgagtc ggtgcttttt 420 tt 422 <210> 19 <211> 471 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 19 tgtacaaaaa agcaggcttt aaaggaacca attcagtcga ctggatccgg taccaaggtc 60 gggcaggaag agggcctatt tcccatgatt ccttcatatt tgcatatacg atacaaggct 120 gttagagaga taattagaat taatttgact gtaaacacaa agatattagt acaaaatacg 180 tgacgtagaa agtaataatt tcttgggtag tttgcagttt taaaattatg ttttaaaatg 240 gactatcata tgcttaccgt aacttgaaag tatttcgatt tcttggcttt atatatcttg 300 tggaaaggac gaaacacccg agacgattaa tgcgtctcgg tttttgtact ctcaagattt 360 aagtaactgt acaacgaaac ttacacagtt acttaaatct tgcagaagct acaaagataa 420 ggcttcatgc cgaaatcaac accctgtcat tttatggcag ggtgtttttt t 471 <210> 20 <211> 466 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 20 tgtacaaaaa agcaggcttt aaaggaacca attcagtcga ctggatccgg taccaaggtc 60 gggcaggaag agggcctatt tcccatgatt ccttcatatt tgcatatacg atacaaggct 120 gttagagaga taattagaat taatttgact gtaaacacaa agatattagt acaaaatacg 180 tgacgtagaa agtaataatt tcttgggtag tttgcagttt taaaattatg ttttaaaatg 240 gactatcata tgcttaccgt aacttgaaag tatttcgatt tcttggcttt atatatcttg 300 tggaaaggac gaaacacccg agacgattaa tgcgtctcgg ttttagtact ctgtaatttt 360 aggtatgagg tagacgaaaa ttgtacttat acctaaaatt acagaatcta ctaaaacaag 420 gcaaaatgcc gtgtttatct cgtcaacttg ttggcgagat tttttt 466 <210> 21 <211> 3609 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 21 taatacgact cactataggg gaattgtgag cggataacaa ttcccctgta gaaataattt 60 tgtttaactt taataaggag atataccatg ggcaaacgga actacatcct ggggcttgac 120 attgggataa ccagcgttgg ctacggaatt attgattatg agacacgcga tgtgattgac 180 gccggggtta ggctgttcaa agaggccaac gttgaaaaca acgagggaag acggagtaag 240 cgcggagcaa gaagactcaa gcgcagacgg agacatcgga ttcagagggt gaaaaagctg 300 ctcttcgatt acaatctcct gaccgatcat agtgagctga gcggaatcaa cccctacgag 360 gcgcgagtga aagggctttc ccagaagctg tccgaagagg agttctccgc cgcgttgctg 420 cacctggcca aacggagggg ggttcacaat gtaaacgaag tggaggagga cacgggcaat 480 gaacttagta cgaaagaaca gatcagtagg aactctaagg ctctcgaaga gaaatacgtc 540 gctgagttgc agcttgagag actgaaaaaa gacggcgaag tacgcggatc tattaatagg 600 ttcaagactt cagattacgt aaaggaagcc aagcagctcc tgaaagtaca gaaagcgtac 660 catcagctcg atcagagctt catcgatacc tacatagatt tgctggagac acggaggaca 720 tactacgagg gcccagggga aggatctcct tttgggtgga aggacatcaa ggaatggtac 780 gagatgctta tgggacattg tacatatttt ccggaggagc tcaggagcgt caagtacgcc 840 tacaatgccg acctgtacaa tgccctcaat gacctcaata acctcgtgat taccagggac 900 gagaacgaga agctggagta ctatgaaaag ttccagatta tcgagaatgt gtttaagcag 960 aagaagaagc cgacacttaa gcagattgca aaggaaatcc tcgtgaatga ggaagatatc 1020 aagggataca gagtgacaag tacaggcaag cccgagttca caaatctgaa ggtgtaccac 1080 gatattaagg acataaccgc acgaaaggag ataatcgaaa acgctgagct cctcgatcag 1140 atcgcaaaaa ttcttaccat ctaccagtct agtgaggaca ttcaggagga actgactaat 1200 ctgaacagtg agctcaccca agaggaaatt gagcagattt caaacctgaa aggctacacc 1260 gggacgcaca atctgagcct caaagcaatc aacctcattc tggatgaact ttggcacaca 1320 aatgacaacc aaattgccat attcaaccgc ctgaaactgg tgccaaaaaa agtggatctg 1380 tcacagcaaa aggaaatccc tacaaccttg gttgacgatt ttattctgtc ccccgttgtc 1440 aagcggagct tcatccagtc aatcaaggtg atcaatgcca tcattaaaaa atacggattg 1500 ccaaacgata taattatcga gcttgcacga gagaagaact caaaggacgc ccagaagatg 1560 attaacgaaa tgcagaagcg caaccgccag acaaacgaac gcatagagga aattataaga 1620 acaaccggca aagagaatgc caagtatctg atcgagaaaa tcaagctgca cgacatgcaa 1680 gaaggcaagt gcctgtactc tctggaagct atcccactcg aagatctgct gaataatcca 1740 ttcaattacg aggtggacca catcatccct agatccgtaa gctttgacaa ttccttcaat 1800 aacaaagttc tggttaaaca ggaggaaaat tctaaaaaag ggaaccggac cccgttccag 1860 tacctgagct ccagtgacag caagattagc tacgagactt ttaagaaaca tattctgaat 1920 ctggccaaag gcaaaggcag gatcagcaag accaagaagg agtacctcct cgaagaacgc 1980 gacattaaca gatttagtgt gcagaaagat ttcatcaacc gaaaccttgt cgatactcgg 2040 tacgccacga gaggcctgat gaatctcctc aggagctact tccgcgtcaa taatctggac 2100 gttaaagtca agagcataaa tgggggattc accagctttc tgaggagaaa gtggaagttt 2160 aagaaggaac gaaacaaagg atacaagcac catgctgagg atgctttgat catcgctaac 2220 gcggacttta tctttaagga atggaaaaag ctggataagg caaagaaagt gatggaaaac 2280 cagatgttcg aggagaagca ggcagagtca atgcctgaga tcgagacaga gcaggaatac 2340 aaggaaattt tcatcacccc tcatcagatt aaacacataa aggacttcaa agactataaa 2400 tactctcata gggtggacaa aaaacccaat cgcgagctca ttaatgacac cctgtactca 2460 acacggaagg atgataaagg taataccttg attgtgaata atcttaatgg attgtatgac 2520 aaagataacg acaagctcaa gaagctgatc aacaagtctc cagagaagct ccttatgtat 2580 caccacgacc cacagactta tcagaaattg aaactgatca tggagcaata cggggatgag 2640 aagaacccac tctacaaata ttatgaggaa acaggtaatt acctgaccaa gtactccaag 2700 aaggataacg gaccagtgat caaaaagata aagtactatg gcaacaaact taatgcgcat 2760 ttggacataa ctgacgatta ccccaattct cgaaacaagg ttgtgaagct ctccctgaag 2820 ccttatagat ttgacgtgta cctggataat ggggtttata aattcgtcac cgtgaaaaat 2880 ctggacgtga tcaaaaagga gaactattat gaagtaaact caaagtgcta tgaggaggcg 2940 aagaagctga agaagatctc caatcaggcc gagttcatcg cttccttcta taataacgat 3000 ctcatcaaga tcaatggaga gctttatcgc gtcattggtg tgaacaatga cttgctgaac 3060 aggatcgaag tcaatatgat agacattacc taccgggagt atctcgaaaa catgaatgat 3120 aaacggccgc ctcgcatcat caagacaatc gcatctaaaa ctcagtcaat aaaaaagtac 3180 tctaccgata tcctggggaa tctctatgaa gtgaagtcaa agaagcaccc acaaatcatt 3240 aaaaaaggtg gatcccccaa gaagaagagg aaagtctcga gcgactacaa agaccatgac 3300 ggtgattata aagatcatga catcgattac aaggatgacg atgacaagta aagcggccgc 3360 ataatgctta agtcgaacag aaagtaatcg tattgtacac ggccgcataa tcgaaattaa 3420 tacgactcac tataggggca cgggcagctt gccgggtttt agtactctgt aatgaaaatt 3480 acagaatcta ctaaaacaag gcaaaatgcc gtgtttatct cgtcaacttg ttggcgagat 3540 tttttttccg ctgagcaata actagcataa ccccttgggg cctctaaacg ggtcttgagg 3600 ggttttttg 3609 <210> 22 <211> 3609 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 22 taatacgact cactataggg gaattgtgag cggataacaa ttcccctgta gaaataattt 60 tgtttaactt taataaggag atataccatg ggcaaacgga actacatcct ggggcttgcc 120 attgggataa ccagcgttgg ctacggaatt attgattatg agacacgcga tgtgattgac 180 gccggggtta ggctgttcaa agaggccaac gttgaaaaca acgagggaag acggagtaag 240 cgcggagcaa gaagactcaa gcgcagacgg agacatcgga ttcagagggt gaaaaagctg 300 ctcttcgatt acaatctcct gaccgatcat agtgagctga gcggaatcaa cccctacgag 360 gcgcgagtga aagggctttc ccagaagctg tccgaagagg agttctccgc cgcgttgctg 420 cacctggcca aacggagggg ggttcacaat gtaaacgaag tggaggagga cacgggcaat 480 gaacttagta cgaaagaaca gatcagtagg aactctaagg ctctcgaaga gaaatacgtc 540 gctgagttgc agcttgagag actgaaaaaa gacggcgaag tacgcggatc tattaatagg 600 ttcaagactt cagattacgt aaaggaagcc aagcagctcc tgaaagtaca gaaagcgtac 660 catcagctcg atcagagctt catcgatacc tacatagatt tgctggagac acggaggaca 720 tactacgagg gcccagggga aggatctcct tttgggtgga aggacatcaa ggaatggtac 780 gagatgctta tgggacattg tacatatttt ccggaggagc tcaggagcgt caagtacgcc 840 tacaatgccg acctgtacaa tgccctcaat gacctcaata acctcgtgat taccagggac 900 gagaacgaga agctggagta ctatgaaaag ttccagatta tcgagaatgt gtttaagcag 960 aagaagaagc cgacacttaa gcagattgca aaggaaatcc tcgtgaatga ggaagatatc 1020 aagggataca gagtgacaag tacaggcaag cccgagttca caaatctgaa ggtgtaccac 1080 gatattaagg acataaccgc acgaaaggag ataatcgaaa acgctgagct cctcgatcag 1140 atcgcaaaaa ttcttaccat ctaccagtct agtgaggaca ttcaggagga actgactaat 1200 ctgaacagtg agctcaccca agaggaaatt gagcagattt caaacctgaa aggctacacc 1260 gggacgcaca atctgagcct caaagcaatc aacctcattc tggatgaact ttggcacaca 1320 aatgacaacc aaattgccat attcaaccgc ctgaaactgg tgccaaaaaa agtggatctg 1380 tcacagcaaa aggaaatccc tacaaccttg gttgacgatt ttattctgtc ccccgttgtc 1440 aagcggagct tcatccagtc aatcaaggtg atcaatgcca tcattaaaaa atacggattg 1500 ccaaacgata taattatcga gcttgcacga gagaagaact caaaggacgc ccagaagatg 1560 attaacgaaa tgcagaagcg caaccgccag acaaacgaac gcatagagga aattataaga 1620 acaaccggca aagagaatgc caagtatctg atcgagaaaa tcaagctgca cgacatgcaa 1680 gaaggcaagt gcctgtactc tctggaagct atcccactcg aagatctgct gaataatcca 1740 ttcaattacg aggtggacgc catcatccct agatccgtaa gctttgacaa ttccttcaat 1800 aacaaagttc tggttaaaca ggaggaaaat tctaaaaaag ggaaccggac cccgttccag 1860 tacctgagct ccagtgacag caagattagc tacgagactt ttaagaaaca tattctgaat 1920 ctggccaaag gcaaaggcag gatcagcaag accaagaagg agtacctcct cgaagaacgc 1980 gacattaaca gatttagtgt gcagaaagat ttcatcaacc gaaaccttgt cgatactcgg 2040 tacgccacga gaggcctgat gaatctcctc aggagctact tccgcgtcaa taatctggac 2100 gttaaagtca agagcataaa tgggggattc accagctttc tgaggagaaa gtggaagttt 2160 aagaaggaac gaaacaaagg atacaagcac catgctgagg atgctttgat catcgctaac 2220 gcggacttta tctttaagga atggaaaaag ctggataagg caaagaaagt gatggaaaac 2280 cagatgttcg aggagaagca ggcagagtca atgcctgaga tcgagacaga gcaggaatac 2340 aaggaaattt tcatcacccc tcatcagatt aaacacataa aggacttcaa agactataaa 2400 tactctcata gggtggacaa aaaacccaat cgcgagctca ttaatgacac cctgtactca 2460 acacggaagg atgataaagg taataccttg attgtgaata atcttaatgg attgtatgac 2520 aaagataacg acaagctcaa gaagctgatc aacaagtctc cagagaagct ccttatgtat 2580 caccacgacc cacagactta tcagaaattg aaactgatca tggagcaata cggggatgag 2640 aagaacccac tctacaaata ttatgaggaa acaggtaatt acctgaccaa gtactccaag 2700 aaggataacg gaccagtgat caaaaagata aagtactatg gcaacaaact taatgcgcat 2760 ttggacataa ctgacgatta ccccaattct cgaaacaagg ttgtgaagct ctccctgaag 2820 ccttatagat ttgacgtgta cctggataat ggggtttata aattcgtcac cgtgaaaaat 2880 ctggacgtga tcaaaaagga gaactattat gaagtaaact caaagtgcta tgaggaggcg 2940 aagaagctga agaagatctc caatcaggcc gagttcatcg cttccttcta taataacgat 3000 ctcatcaaga tcaatggaga gctttatcgc gtcattggtg tgaacaatga cttgctgaac 3060 aggatcgaag tcaatatgat agacattacc taccgggagt atctcgaaaa catgaatgat 3120 aaacggccgc ctcgcatcat caagacaatc gcatctaaaa ctcagtcaat aaaaaagtac 3180 tctaccgata tcctggggaa tctctatgaa gtgaagtcaa agaagcaccc acaaatcatt 3240 aaaaaaggtg gatcccccaa gaagaagagg aaagtctcga gcgactacaa agaccatgac 3300 ggtgattata aagatcatga catcgattac aaggatgacg atgacaagta aagcggccgc 3360 ataatgctta agtcgaacag aaagtaatcg tattgtacac ggccgcataa tcgaaattaa 3420 tacgactcac tataggggca cgggcagctt gccgggtttt agtactctgt aatgaaaatt 3480 acagaatcta ctaaaacaag gcaaaatgcc gtgtttatct cgtcaacttg ttggcgagat 3540 tttttttccg ctgagcaata actagcataa ccccttgggg cctctaaacg ggtcttgagg 3600 ggttttttg 3609 <210> 23 <211> 3609 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 23 taatacgact cactataggg gaattgtgag cggataacaa ttcccctgta gaaataattt 60 tgtttaactt taataaggag atataccatg ggcaaacgga actacatcct ggggcttgac 120 attgggataa ccagcgttgg ctacggaatt attgattatg agacacgcga tgtgattgac 180 gccggggtta ggctgttcaa agaggccaac gttgaaaaca acgagggaag acggagtaag 240 cgcggagcaa gaagactcaa gcgcagacgg agacatcgga ttcagagggt gaaaaagctg 300 ctcttcgatt acaatctcct gaccgatcat agtgagctga gcggaatcaa cccctacgag 360 gcgcgagtga aagggctttc ccagaagctg tccgaagagg agttctccgc cgcgttgctg 420 cacctggcca aacggagggg ggttcacaat gtaaacgaag tggaggagga cacgggcaat 480 gaacttagta cgaaagaaca gatcagtagg aactctaagg ctctcgaaga gaaatacgtc 540 gctgagttgc agcttgagag actgaaaaaa gacggcgaag tacgcggatc tattaatagg 600 ttcaagactt cagattacgt aaaggaagcc aagcagctcc tgaaagtaca gaaagcgtac 660 catcagctcg atcagagctt catcgatacc tacatagatt tgctggagac acggaggaca 720 tactacgagg gcccagggga aggatctcct tttgggtgga aggacatcaa ggaatggtac 780 gagatgctta tgggacattg tacatatttt ccggaggagc tcaggagcgt caagtacgcc 840 tacaatgccg acctgtacaa tgccctcaat gacctcaata acctcgtgat taccagggac 900 gagaacgaga agctggagta ctatgaaaag ttccagatta tcgagaatgt gtttaagcag 960 aagaagaagc cgacacttaa gcagattgca aaggaaatcc tcgtgaatga ggaagatatc 1020 aagggataca gagtgacaag tacaggcaag cccgagttca caaatctgaa ggtgtaccac 1080 gatattaagg acataaccgc acgaaaggag ataatcgaaa acgctgagct cctcgatcag 1140 atcgcaaaaa ttcttaccat ctaccagtct agtgaggaca ttcaggagga actgactaat 1200 ctgaacagtg agctcaccca agaggaaatt gagcagattt caaacctgaa aggctacacc 1260 gggacgcaca atctgagcct caaagcaatc aacctcattc tggatgaact ttggcacaca 1320 aatgacaacc aaattgccat attcaaccgc ctgaaactgg tgccaaaaaa agtggatctg 1380 tcacagcaaa aggaaatccc tacaaccttg gttgacgatt ttattctgtc ccccgttgtc 1440 aagcggagct tcatccagtc aatcaaggtg atcaatgcca tcattaaaaa atacggattg 1500 ccaaacgata taattatcga gcttgcacga gagaagaact caaaggacgc ccagaagatg 1560 attaacgaaa tgcagaagcg caaccgccag acaaacgaac gcatagagga aattataaga 1620 acaaccggca aagagaatgc caagtatctg atcgagaaaa tcaagctgca cgacatgcaa 1680 gaaggcaagt gcctgtactc tctggaagct atcccactcg aagatctgct gaataatcca 1740 ttcaattacg aggtggacca catcatccct agatccgtaa gctttgacaa ttccttcaat 1800 aacaaagttc tggttaaaca ggaggaaaat tctaaaaaag ggaaccggac cccgttccag 1860 tacctgagct ccagtgacag caagattagc tacgagactt ttaagaaaca tattctgaat 1920 ctggccaaag gcaaaggcag gatcagcaag accaagaagg agtacctcct cgaagaacgc 1980 gacattaaca gatttagtgt gcagaaagat ttcatcaacc gaaaccttgt cgatactcgg 2040 tacgccacga gaggcctgat gaatctcctc aggagctact tccgcgtcaa taatctggac 2100 gttaaagtca agagcataaa tgggggattc accagctttc tgaggagaaa gtggaagttt 2160 aagaaggaac gaaacaaagg atacaagcac catgctgagg atgctttgat catcgctaac 2220 gcggacttta tctttaagga atggaaaaag ctggataagg caaagaaagt gatggaaaac 2280 cagatgttcg aggagaagca ggcagagtca atgcctgaga tcgagacaga gcaggaatac 2340 aaggaaattt tcatcacccc tcatcagatt aaacacataa aggacttcaa agactataaa 2400 tactctcata gggtggacaa aaaacccaat cgcaagctca ttaatgacac cctgtactca 2460 acacggaagg atgataaagg taataccttg attgtgaata atcttaatgg attgtatgac 2520 aaagataacg acaagctcaa gaagctgatc aacaagtctc cagagaagct ccttatgtat 2580 caccacgacc cacagactta tcagaaattg aaactgatca tggagcaata cggggatgag 2640 aagaacccac tctacaaata ttatgaggaa acaggtaatt acctgaccaa gtactccaag 2700 aaggataacg gaccagtgat caaaaagata aagtactatg gcaacaaact taatgcgcat 2760 ttggacataa ctgacgatta ccccaattct cgaaacaagg ttgtgaagct ctccctgaag 2820 ccttatagat ttgacgtgta cctggataat ggggtttata aattcgtcac cgtgaaaaat 2880 ctggacgtga tcaaaaagga gaactattat gaagtaaact caaagtgcta tgaggaggcg 2940 aagaagctga agaagatctc caatcaggcc gagttcatcg cttccttcta taagaacgat 3000 ctcatcaaga tcaatggaga gctttatcgc gtcattggtg tgaacaatga cttgctgaac 3060 aggatcgaag tcaatatgat agacattacc taccgggagt atctcgaaaa catgaatgat 3120 aaacggccgc ctcacatcat caagacaatc gcatctaaaa ctcagtcaat aaaaaagtac 3180 tctaccgata tcctggggaa tctctatgaa gtgaagtcaa agaagcaccc acaaatcatt 3240 aaaaaaggtg gatcccccaa gaagaagagg aaagtctcga gcgactacaa agaccatgac 3300 ggtgattata aagatcatga catcgattac aaggatgacg atgacaagta aagcggccgc 3360 ataatgctta agtcgaacag aaagtaatcg tattgtacac ggccgcataa tcgaaattaa 3420 tacgactcac tataggggca cgggcagctt gccgggtttt agtactctgt aatgaaaatt 3480 acagaatcta ctaaaacaag gcaaaatgcc gtgtttatct cgtcaacttg ttggcgagat 3540 tttttttccg ctgagcaata actagcataa ccccttgggg cctctaaacg ggtcttgagg 3600 ggttttttg 3609 <210> 24 <211> 3609 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 24 taatacgact cactataggg gaattgtgag cggataacaa ttcccctgta gaaataattt 60 tgtttaactt taataaggag atataccatg ggcaaacgga actacatcct ggggcttgac 120 attgggataa ccagcgttgg ctacggaatt attgattatg agacacgcga tgtgattgac 180 gccggggtta ggctgttcaa agaggccaac gttgaaaaca acgagggaag acggagtaag 240 cgcggagcaa gaagactcaa gcgcagacgg agacatcgga ttcagagggt gaaaaagctg 300 ctcttcgatt acaatctcct gaccgatcat agtgagctga gcggaatcaa cccctacgag 360 gcgcgagtga aagggctttc ccagaagctg tccgaagagg agttctccgc cgcgttgctg 420 cacctggcca aacggagggg ggttcacaat gtaaacgaag tggaggagga cacgggcaat 480 gaacttagta cgaaagaaca gatcagtagg aactctaagg ctctcgaaga gaaatacgtc 540 gctgagttgc agcttgagag actgaaaaaa gacggcgaag tacgcggatc tattaatagg 600 ttcaagactt cagattacgt aaaggaagcc aagcagctcc tgaaagtaca gaaagcgtac 660 catcagctcg atcagagctt catcgatacc tacatagatt tgctggagac acggaggaca 720 tactacgagg gcccagggga aggatctcct tttgggtgga aggacatcaa ggaatggtac 780 gagatgctta tgggacattg tacatatttt ccggaggagc tcaggagcgt caagtacgcc 840 tacaatgccg acctgtacaa tgccctcaat gacctcaata acctcgtgat taccagggac 900 gagaacgaga agctggagta ctatgaaaag ttccagatta tcgagaatgt gtttaagcag 960 aagaagaagc cgacacttaa gcagattgca aaggaaatcc tcgtgaatga ggaagatatc 1020 aagggataca gagtgacaag tacaggcaag cccgagttca caaatctgaa ggtgtaccac 1080 gatattaagg acataaccgc acgaaaggag ataatcgaaa acgctgagct cctcgatcag 1140 atcgcaaaaa ttcttaccat ctaccagtct agtgaggaca ttcaggagga actgactaat 1200 ctgaacagtg agctcaccca agaggaaatt gagcagattt caaacctgaa aggctacacc 1260 gggacgcaca atctgagcct caaagcaatc aacctcattc tggatgaact ttggcacaca 1320 aatgacaacc aaattgccat attcaaccgc ctgaaactgg tgccaaaaaa agtggatctg 1380 tcacagcaaa aggaaatccc tacaaccttg gttgacgatt ttattctgtc ccccgttgtc 1440 aagcggagct tcatccagtc aatcaaggtg atcaatgcca tcattaaaaa atacggattg 1500 ccaaacgata taattatcga gcttgcacga gagaagaact caaaggacgc ccagaagatg 1560 attaacgaaa tgcagaagcg caaccgccag acaaacgaac gcatagagga aattataaga 1620 acaaccggca aagagaatgc caagtatctg atcgagaaaa tcaagctgca cgacatgcaa 1680 gaaggcaagt gcctgtactc tctggaagct atcccactcg aagatctgct gaataatcca 1740 ttcaattacg aggtggacca catcatccct agatccgtaa gctttgacaa ttccttcaat 1800 aacaaagttc tggttaaaca ggaggaaaat tctaaaaaag ggaaccggac cccgttccag 1860 tacctgagct ccagtgacag caagattagc tacgagactt ttaagaaaca tattctgaat 1920 ctggccaaag gcaaaggcag gatcagcaag accaagaagg agtacctcct cgaagaacgc 1980 gacattaaca gatttagtgt gcagaaagat ttcatcaacc gaaaccttgt cgatactcgg 2040 tacgccacga gaggcctgat gaatctcctc aggagctact tccgcgtcaa taatctggac 2100 gttaaagtca agagcataaa tgggggattc accagctttc tgaggagaaa gtggaagttt 2160 aagaaggaac gaaacaaagg atacaagcac catgctgagg atgctttgat catcgctaac 2220 gcggacttta tctttaagga atggaaaaag ctggataagg caaagaaagt gatggaaaac 2280 cagatgttcg aggagaagca ggcagagtca atgcctgaga tcgagacaga gcaggaatac 2340 aaggaaattt tcatcacccc tcatcagatt aaacacataa aggacttcaa agactataaa 2400 tactctcata gggtggacaa aaaacccaat cgcgagctca ttaatgacac cctgtactca 2460 acacggaagg atgataaagg taataccttg attgtgaata atcttaatgg attgtatgac 2520 aaagataacg acaagctcaa gaagctgatc aacaagtctc cagagaagct ccttatgtat 2580 caccacgacc cacagactta tcagaaattg aaactgatca tggagcaata cggggatgag 2640 aagaacccac tctacaaata ttatgaggaa acaggtaatt acctgaccaa gtactccaag 2700 aaggataacg gaccagtgat caaaaagata aagtactatg gcaacaaact taatgcgcat 2760 ttggacataa ctgacgatta ccccaattct cgaaacaagg ttgtgaagct ctccctgaag 2820 ccttatagat ttgacgtgta cctggataat ggggtttata aattcgtcac cgtgaaaaat 2880 ctggacgtga tcaaaaagga gaactattat gaagtaaact caaagtgcta tgaggaggcg 2940 aagaagctga agaagatctc caatcaggcc gagttcatcg cttccttcta taataacgat 3000 ctcatcaaga tcaatggaga gctttatcgc gtcattggtg tgaacaatga cttgctgaac 3060 aggatcgaag tcaatatgat agacattacc taccgggagt atctcgaaaa catgaatgat 3120 aaacggccgc ctcgcatcat caagacaatc gcatctaaaa ctcagtcaat aaaaaagtac 3180 tctaccgata tcctggggaa tctctatgaa gtgaagtcaa agaagcaccc acaaatcatt 3240 aaaaaaggtg gatcccccaa gaagaagagg aaagtctcga gcgactacaa agaccatgac 3300 ggtgattata aagatcatga catcgattac aaggatgacg atgacaagta aagcggccgc 3360 ataatgctta agtcgaacag aaagtaatcg tattgtacac ggccgcataa tcgaaattaa 3420 tacgactcac tataggtcgc cctcgaactt cacctgtttt agtactctgt aatgaaaatt 3480 acagaatcta ctaaaacaag gcaaaatgcc gtgtttatct cgtcaacttg ttggcgagat 3540 tttttttccg ctgagcaata actagcataa ccccttgggg cctctaaacg ggtcttgagg 3600 ggttttttg 3609 <210> 25 <211> 3609 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 25 taatacgact cactataggg gaattgtgag cggataacaa ttcccctgta gaaataattt 60 tgtttaactt taataaggag atataccatg ggcaaacgga actacatcct ggggcttgcc 120 attgggataa ccagcgttgg ctacggaatt attgattatg agacacgcga tgtgattgac 180 gccggggtta ggctgttcaa agaggccaac gttgaaaaca acgagggaag acggagtaag 240 cgcggagcaa gaagactcaa gcgcagacgg agacatcgga ttcagagggt gaaaaagctg 300 ctcttcgatt acaatctcct gaccgatcat agtgagctga gcggaatcaa cccctacgag 360 gcgcgagtga aagggctttc ccagaagctg tccgaagagg agttctccgc cgcgttgctg 420 cacctggcca aacggagggg ggttcacaat gtaaacgaag tggaggagga cacgggcaat 480 gaacttagta cgaaagaaca gatcagtagg aactctaagg ctctcgaaga gaaatacgtc 540 gctgagttgc agcttgagag actgaaaaaa gacggcgaag tacgcggatc tattaatagg 600 ttcaagactt cagattacgt aaaggaagcc aagcagctcc tgaaagtaca gaaagcgtac 660 catcagctcg atcagagctt catcgatacc tacatagatt tgctggagac acggaggaca 720 tactacgagg gcccagggga aggatctcct tttgggtgga aggacatcaa ggaatggtac 780 gagatgctta tgggacattg tacatatttt ccggaggagc tcaggagcgt caagtacgcc 840 tacaatgccg acctgtacaa tgccctcaat gacctcaata acctcgtgat taccagggac 900 gagaacgaga agctggagta ctatgaaaag ttccagatta tcgagaatgt gtttaagcag 960 aagaagaagc cgacacttaa gcagattgca aaggaaatcc tcgtgaatga ggaagatatc 1020 aagggataca gagtgacaag tacaggcaag cccgagttca caaatctgaa ggtgtaccac 1080 gatattaagg acataaccgc acgaaaggag ataatcgaaa acgctgagct cctcgatcag 1140 atcgcaaaaa ttcttaccat ctaccagtct agtgaggaca ttcaggagga actgactaat 1200 ctgaacagtg agctcaccca agaggaaatt gagcagattt caaacctgaa aggctacacc 1260 gggacgcaca atctgagcct caaagcaatc aacctcattc tggatgaact ttggcacaca 1320 aatgacaacc aaattgccat attcaaccgc ctgaaactgg tgccaaaaaa agtggatctg 1380 tcacagcaaa aggaaatccc tacaaccttg gttgacgatt ttattctgtc ccccgttgtc 1440 aagcggagct tcatccagtc aatcaaggtg atcaatgcca tcattaaaaa atacggattg 1500 ccaaacgata taattatcga gcttgcacga gagaagaact caaaggacgc ccagaagatg 1560 attaacgaaa tgcagaagcg caaccgccag acaaacgaac gcatagagga aattataaga 1620 acaaccggca aagagaatgc caagtatctg atcgagaaaa tcaagctgca cgacatgcaa 1680 gaaggcaagt gcctgtactc tctggaagct atcccactcg aagatctgct gaataatcca 1740 ttcaattacg aggtggacgc catcatccct agatccgtaa gctttgacaa ttccttcaat 1800 aacaaagttc tggttaaaca ggaggaaaat tctaaaaaag ggaaccggac cccgttccag 1860 tacctgagct ccagtgacag caagattagc tacgagactt ttaagaaaca tattctgaat 1920 ctggccaaag gcaaaggcag gatcagcaag accaagaagg agtacctcct cgaagaacgc 1980 gacattaaca gatttagtgt gcagaaagat ttcatcaacc gaaaccttgt cgatactcgg 2040 tacgccacga gaggcctgat gaatctcctc aggagctact tccgcgtcaa taatctggac 2100 gttaaagtca agagcataaa tgggggattc accagctttc tgaggagaaa gtggaagttt 2160 aagaaggaac gaaacaaagg atacaagcac catgctgagg atgctttgat catcgctaac 2220 gcggacttta tctttaagga atggaaaaag ctggataagg caaagaaagt gatggaaaac 2280 cagatgttcg aggagaagca ggcagagtca atgcctgaga tcgagacaga gcaggaatac 2340 aaggaaattt tcatcacccc tcatcagatt aaacacataa aggacttcaa agactataaa 2400 tactctcata gggtggacaa aaaacccaat cgcgagctca ttaatgacac cctgtactca 2460 acacggaagg atgataaagg taataccttg attgtgaata atcttaatgg attgtatgac 2520 aaagataacg acaagctcaa gaagctgatc aacaagtctc cagagaagct ccttatgtat 2580 caccacgacc cacagactta tcagaaattg aaactgatca tggagcaata cggggatgag 2640 aagaacccac tctacaaata ttatgaggaa acaggtaatt acctgaccaa gtactccaag 2700 aaggataacg gaccagtgat caaaaagata aagtactatg gcaacaaact taatgcgcat 2760 ttggacataa ctgacgatta ccccaattct cgaaacaagg ttgtgaagct ctccctgaag 2820 ccttatagat ttgacgtgta cctggataat ggggtttata aattcgtcac cgtgaaaaat 2880 ctggacgtga tcaaaaagga gaactattat gaagtaaact caaagtgcta tgaggaggcg 2940 aagaagctga agaagatctc caatcaggcc gagttcatcg cttccttcta taataacgat 3000 ctcatcaaga tcaatggaga gctttatcgc gtcattggtg tgaacaatga cttgctgaac 3060 aggatcgaag tcaatatgat agacattacc taccgggagt atctcgaaaa catgaatgat 3120 aaacggccgc ctcgcatcat caagacaatc gcatctaaaa ctcagtcaat aaaaaagtac 3180 tctaccgata tcctggggaa tctctatgaa gtgaagtcaa agaagcaccc acaaatcatt 3240 aaaaaaggtg gatcccccaa gaagaagagg aaagtctcga gcgactacaa agaccatgac 3300 ggtgattata aagatcatga catcgattac aaggatgacg atgacaagta aagcggccgc 3360 ataatgctta agtcgaacag aaagtaatcg tattgtacac ggccgcataa tcgaaattaa 3420 tacgactcac tataggtcgc cctcgaactt cacctgtttt agtactctgt aatgaaaatt 3480 acagaatcta ctaaaacaag gcaaaatgcc gtgtttatct cgtcaacttg ttggcgagat 3540 tttttttccg ctgagcaata actagcataa ccccttgggg cctctaaacg ggtcttgagg 3600 ggttttttg 3609 <210> 26 <211> 3609 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 26 taatacgact cactataggg gaattgtgag cggataacaa ttcccctgta gaaataattt 60 tgtttaactt taataaggag atataccatg ggcaaacgga actacatcct ggggcttgac 120 attgggataa ccagcgttgg ctacggaatt attgattatg agacacgcga tgtgattgac 180 gccggggtta ggctgttcaa agaggccaac gttgaaaaca acgagggaag acggagtaag 240 cgcggagcaa gaagactcaa gcgcagacgg agacatcgga ttcagagggt gaaaaagctg 300 ctcttcgatt acaatctcct gaccgatcat agtgagctga gcggaatcaa cccctacgag 360 gcgcgagtga aagggctttc ccagaagctg tccgaagagg agttctccgc cgcgttgctg 420 cacctggcca aacggagggg ggttcacaat gtaaacgaag tggaggagga cacgggcaat 480 gaacttagta cgaaagaaca gatcagtagg aactctaagg ctctcgaaga gaaatacgtc 540 gctgagttgc agcttgagag actgaaaaaa gacggcgaag tacgcggatc tattaatagg 600 ttcaagactt cagattacgt aaaggaagcc aagcagctcc tgaaagtaca gaaagcgtac 660 catcagctcg atcagagctt catcgatacc tacatagatt tgctggagac acggaggaca 720 tactacgagg gcccagggga aggatctcct tttgggtgga aggacatcaa ggaatggtac 780 gagatgctta tgggacattg tacatatttt ccggaggagc tcaggagcgt caagtacgcc 840 tacaatgccg acctgtacaa tgccctcaat gacctcaata acctcgtgat taccagggac 900 gagaacgaga agctggagta ctatgaaaag ttccagatta tcgagaatgt gtttaagcag 960 aagaagaagc cgacacttaa gcagattgca aaggaaatcc tcgtgaatga ggaagatatc 1020 aagggataca gagtgacaag tacaggcaag cccgagttca caaatctgaa ggtgtaccac 1080 gatattaagg acataaccgc acgaaaggag ataatcgaaa acgctgagct cctcgatcag 1140 atcgcaaaaa ttcttaccat ctaccagtct agtgaggaca ttcaggagga actgactaat 1200 ctgaacagtg agctcaccca agaggaaatt gagcagattt caaacctgaa aggctacacc 1260 gggacgcaca atctgagcct caaagcaatc aacctcattc tggatgaact ttggcacaca 1320 aatgacaacc aaattgccat attcaaccgc ctgaaactgg tgccaaaaaa agtggatctg 1380 tcacagcaaa aggaaatccc tacaaccttg gttgacgatt ttattctgtc ccccgttgtc 1440 aagcggagct tcatccagtc aatcaaggtg atcaatgcca tcattaaaaa atacggattg 1500 ccaaacgata taattatcga gcttgcacga gagaagaact caaaggacgc ccagaagatg 1560 attaacgaaa tgcagaagcg caaccgccag acaaacgaac gcatagagga aattataaga 1620 acaaccggca aagagaatgc caagtatctg atcgagaaaa tcaagctgca cgacatgcaa 1680 gaaggcaagt gcctgtactc tctggaagct atcccactcg aagatctgct gaataatcca 1740 ttcaattacg aggtggacca catcatccct agatccgtaa gctttgacaa ttccttcaat 1800 aacaaagttc tggttaaaca ggaggaaaat tctaaaaaag ggaaccggac cccgttccag 1860 tacctgagct ccagtgacag caagattagc tacgagactt ttaagaaaca tattctgaat 1920 ctggccaaag gcaaaggcag gatcagcaag accaagaagg agtacctcct cgaagaacgc 1980 gacattaaca gatttagtgt gcagaaagat ttcatcaacc gaaaccttgt cgatactcgg 2040 tacgccacga gaggcctgat gaatctcctc aggagctact tccgcgtcaa taatctggac 2100 gttaaagtca agagcataaa tgggggattc accagctttc tgaggagaaa gtggaagttt 2160 aagaaggaac gaaacaaagg atacaagcac catgctgagg atgctttgat catcgctaac 2220 gcggacttta tctttaagga atggaaaaag ctggataagg caaagaaagt gatggaaaac 2280 cagatgttcg aggagaagca ggcagagtca atgcctgaga tcgagacaga gcaggaatac 2340 aaggaaattt tcatcacccc tcatcagatt aaacacataa aggacttcaa agactataaa 2400 tactctcata gggtggacaa aaaacccaat cgcaagctca ttaatgacac cctgtactca 2460 acacggaagg atgataaagg taataccttg attgtgaata atcttaatgg attgtatgac 2520 aaagataacg acaagctcaa gaagctgatc aacaagtctc cagagaagct ccttatgtat 2580 caccacgacc cacagactta tcagaaattg aaactgatca tggagcaata cggggatgag 2640 aagaacccac tctacaaata ttatgaggaa acaggtaatt acctgaccaa gtactccaag 2700 aaggataacg gaccagtgat caaaaagata aagtactatg gcaacaaact taatgcgcat 2760 ttggacataa ctgacgatta ccccaattct cgaaacaagg ttgtgaagct ctccctgaag 2820 ccttatagat ttgacgtgta cctggataat ggggtttata aattcgtcac cgtgaaaaat 2880 ctggacgtga tcaaaaagga gaactattat gaagtaaact caaagtgcta tgaggaggcg 2940 aagaagctga agaagatctc caatcaggcc gagttcatcg cttccttcta taagaacgat 3000 ctcatcaaga tcaatggaga gctttatcgc gtcattggtg tgaacaatga cttgctgaac 3060 aggatcgaag tcaatatgat agacattacc taccgggagt atctcgaaaa catgaatgat 3120 aaacggccgc ctcacatcat caagacaatc gcatctaaaa ctcagtcaat aaaaaagtac 3180 tctaccgata tcctggggaa tctctatgaa gtgaagtcaa agaagcaccc acaaatcatt 3240 aaaaaaggtg gatcccccaa gaagaagagg aaagtctcga gcgactacaa agaccatgac 3300 ggtgattata aagatcatga catcgattac aaggatgacg atgacaagta aagcggccgc 3360 ataatgctta agtcgaacag aaagtaatcg tattgtacac ggccgcataa tcgaaattaa 3420 tacgactcac tataggtcgc cctcgaactt cacctgtttt agtactctgt aatgaaaatt 3480 acagaatcta ctaaaacaag gcaaaatgcc gtgtttatct cgtcaacttg ttggcgagat 3540 tttttttccg ctgagcaata actagcataa ccccttgggg cctctaaacg ggtcttgagg 3600 ggttttttg 3609 <210> 27 <211> 3264 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 27 atggggaaac ggaactacat cctggggctt gacattggga taaccagcgt tggctacgga 60 attattgatt atgagacacg cgatgtgatt gacgccgggg ttaggctgtt caaagaggcc 120 aacgttgaaa acaacgaggg aagacggagt aagcgcggag caagaagact caagcgcaga 180 cggagacatc ggattcagag ggtgaaaaag ctgctcttcg attacaatct cctgaccgat 240 catagtgagc tgagcggaat caacccctac gaggcgcgag tgaaagggct ttcccagaag 300 ctgtccgaag aggagttctc cgccgcgttg ctgcacctgg ccaaacggag gggggttcac 360 aatgtaaacg aagtggagga ggacacgggc aatgaactta gtacgaaaga acagatcagt 420 aggaactcta aggctctcga agagaaatac gtcgctgagt tgcagcttga gagactgaaa 480 aaagacggcg aagtacgcgg atctattaat aggttcaaga cttcagatta cgtaaaggaa 540 gccaagcagc tcctgaaagt acagaaagcg taccatcagc tcgatcagag cttcatcgat 600 acctacatag atttgctgga gacacggagg acatactacg agggcccagg ggaaggatct 660 ccttttgggt ggaaggacat caaggaatgg tacgagatgc ttatgggaca ttgtacatat 720 tttccggagg agctcaggag cgtcaagtac gcctacaatg ccgacctgta caatgccctc 780 aatgacctca ataacctcgt gattaccagg gacgagaacg agaagctgga gtactatgaa 840 aagttccaga ttatcgagaa tgtgtttaag cagaagaaga agccgacact taagcagatt 900 gcaaaggaaa tcctcgtgaa tgaggaagat atcaagggat acagagtgac aagtacaggc 960 aagcccgagt tcacaaatct gaaggtgtac cacgatatta aggacataac cgcacgaaag 1020 gagataatcg aaaacgctga gctcctcgat cagatcgcaa aaattcttac catctaccag 1080 tctagtgagg acattcagga ggaactgact aatctgaaca gtgagctcac ccaagaggaa 1140 attgagcaga tttcaaacct gaaaggctac accgggacgc acaatctgag cctcaaagca 1200 atcaacctca ttctggatga actttggcac acaaatgaca accaaattgc catattcaac 1260 cgcctgaaac tggtgccaaa aaaagtggat ctgtcacagc aaaaggaaat ccctacaacc 1320 ttggttgacg attttattct gtcccccgtt gtcaagcgga gcttcatcca gtcaatcaag 1380 gtgatcaatg ccatcattaa aaaatacgga ttgccaaacg atataattat cgagcttgca 1440 cgagagaaga actcaaagga cgcccagaag atgattaacg aaatgcagaa gcgcaaccgc 1500 cagacaaacg aacgcataga ggaaattata agaacaaccg gcaaagagaa tgccaagtat 1560 ctgatcgaga aaatcaagct gcacgacatg caagaaggca agtgcctgta ctctctggaa 1620 gctatcccac tcgaagatct gctgaataat ccattcaatt acgaggtgga ccacatcatc 1680 cctagatccg taagctttga caattccttc aataacaaag ttctggttaa acaggaggaa 1740 aattctaaaa aagggaaccg gaccccgttc cagtacctga gctccagtga cagcaagatt 1800 agctacgaga cttttaagaa acatattctg aatctggcca aaggcaaagg caggatcagc 1860 aagaccaaga aggagtacct cctcgaagaa cgcgacatta acagatttag tgtgcagaaa 1920 gatttcatca accgaaacct tgtcgatact cggtacgcca cgagaggcct gatgaatctc 1980 ctcaggagct acttccgcgt caataatctg gacgttaaag tcaagagcat aaatggggga 2040 ttcaccagct ttctgaggag aaagtggaag tttaagaagg aacgaaacaa aggatacaag 2100 caccatgctg aggatgcttt gatcatcgct aacgcggact ttatctttaa ggaatggaaa 2160 aagctggata aggcaaagaa agtgatggaa aaccagatgt tcgaggagaa gcaggcagag 2220 tcaatgcctg agatcgagac agagcaggaa tacaaggaaa ttttcatcac ccctcatcag 2280 attaaacaca taaaggactt caaagactat aaatactctc atagggtgga caaaaaaccc 2340 aatcgcaagc tcattaatga caccctgtac tcaacacgga aggatgataa aggtaatacc 2400 ttgattgtga ataatcttaa tggattgtat gacaaagata acgacaagct caagaagctg 2460 atcaacaagt ctccagagaa gctccttatg tatcaccacg acccacagac ttatcagaaa 2520 ttgaaactga tcatggagca atacggggat gagaagaacc cactctacaa atattatgag 2580 gaaacaggta attacctgac caagtactcc aagaaggata acggaccagt gatcaaaaag 2640 ataaagtact atggcaacaa acttaatgcg catttggaca taactgacga ttaccccaat 2700 tctcgaaaca aggttgtgaa gctctccctg aagccttata gatttgacgt gtacctggat 2760 aatggggttt ataaattcgt caccgtgaaa aatctggacg tgatcaaaaa ggagaactat 2820 tatgaagtaa actcaaagtg ctatgaggag gcgaagaagc tgaagaagat ctccaatcag 2880 gccgagttca tcgcttcctt ctataagaac gatctcatca agatcaatgg agagctttat 2940 cgcgtcattg gtgtgaacaa tgacttgctg aacaggatcg aagtcaatat gatagacatt 3000 acctaccggg agtatctcga aaacatgaat gataaacggc cgcctcacat catcaagaca 3060 atcgcatcta aaactcagtc aataaaaaag tactctaccg atatcctggg gaatctctat 3120 gaagtgaagt caaagaagca cccacaaatc attaaaaaag gtggatcccc caagaagaag 3180 aggaaagtct cgagcgacta caaagaccat gacggtgatt ataaagatca tgacatcgat 3240 tacaaggatg acgatgacaa gtaa 3264 <210> 28 <211> 430 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polynucleotide <400> 28 tgtacaaaaa agcaggcttt aaaggaacca attcagtcga ctggatccgg taccaaggtc 60 gggcaggaag agggcctatt tcccatgatt ccttcatatt tgcatatacg atacaaggct 120 gttagagaga taattagaat taatttgact gtaaacacaa agatattagt acaaaatacg 180 tgacgtagaa agtaataatt tcttgggtag tttgcagttt taaaattatg ttttaaaatg 240 gactatcata tgcttaccgt aacttgaaag tatttcgatt tcttggcttt atatatcttg 300 tggaaaggac gaaacacccg agacgattaa tgcgtctcgg ttttagtact ctgtaatgaa 360 aattacagaa tctactaaaa caaggcaaaa tgccgtgttt atctcgtcaa cttgttggcg 420 agattttttt 430 <210> 29 <211> 134 <212> PRT <213> Listeria innocua <400> 29 Gln Gln Val Leu Pro Asn His Leu Val Thr Leu Leu His His Ala Ala 1 5 10 15 Asn Cys Glu Val Ser Asp Gly Lys Ser Leu Asp Tyr Ile Glu Ser Asn 20 25 30 Arg Glu Met Phe Ala Glu Leu Leu Ala His Val Ser Glu Phe Ala Lys 35 40 45 Arg Tyr Thr Leu Ala Glu Ala Asn Leu Asn Lys Ile Asn Gln Leu Phe 50 55 60 Glu Gln Asn Lys Glu Gly Asp Ile Lys Ala Ile Ala Gln Ser Phe Val 65 70 75 80 Asp Leu Met Ala Phe Asn Ala Met Gly Ala Pro Ala Ser Phe Lys Phe 85 90 95 Phe Glu Thr Thr Ile Glu Arg Lys Arg Tyr Asn Asn Leu Lys Glu Leu 100 105 110 Leu Asn Ser Thr Ile Ile Tyr Gln Ser Ile Thr Gly Leu Tyr Glu Ser 115 120 125 Arg Lys Arg Leu Asp Asp 130 <210> 30 <211> 139 <212> PRT <213> Streptococcus mutans <400> 30 Glu Ile Val Leu Pro Asn His Leu Gly Thr Leu Leu Tyr His Ala Lys 1 5 10 15 Asn Ile His Lys Val Asp Glu Pro Lys His Leu Asp Tyr Val Asp Lys 20 25 30 His Lys Asp Glu Phe Lys Glu Leu Leu Asp Val Val Ser Asn Phe Ser 35 40 45 Lys Lys Tyr Thr Leu Ala Glu Gly Asn Leu Glu Lys Ile Lys Glu Leu 50 55 60 Tyr Ala Gln Asn Asn Gly Glu Asp Leu Lys Glu Leu Ala Ser Ser Phe 65 70 75 80 Ile Asn Leu Leu Thr Phe Thr Ala Ile Gly Ala Pro Ala Thr Phe Lys 85 90 95 Phe Phe Asp Lys Asn Ile Asp Arg Lys Arg Tyr Thr Ser Thr Thr Glu 100 105 110 Ile Leu Asn Ala Thr Leu Ile His Gln Ser Ile Thr Gly Leu Tyr Glu 115 120 125 Thr Arg Ile Asp Leu Asn Lys Leu Gly Gly Asp 130 135 <210> 31 <211> 148 <212> PRT <213> Streptococcus thermophilus <400> 31 Gln Ile Phe Leu Ser Gln Lys Phe Val Lys Leu Leu Tyr His Ala Lys 1 5 10 15 Arg Ile Ser Asn Thr Ile Asn Glu Asn His Arg Lys Tyr Val Glu Asn 20 25 30 His Lys Lys Glu Phe Glu Glu Leu Phe Tyr Tyr Ile Leu Glu Phe Asn 35 40 45 Glu Asn Tyr Val Gly Ala Lys Lys Asn Gly Lys Leu Leu Asn Ser Ala 50 55 60 Phe Gln Ser Trp Gln Asn His Ser Ile Asp Glu Leu Cys Ser Ser Phe 65 70 75 80 Ile Gly Pro Thr Gly Ser Glu Arg Lys Gly Leu Phe Glu Leu Thr Ser 85 90 95 Arg Gly Ser Ala Ala Asp Phe Glu Phe Leu Gly Val Lys Ile Pro Arg 100 105 110 Tyr Arg Asp Tyr Thr Pro Ser Ser Leu Leu Lys Asp Ala Thr Leu Ile 115 120 125 His Gln Ser Val Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ala Lys 130 135 140 Leu Gly Glu Gly 145 <210> 32 <211> 175 <212> PRT <213> Francisella novicida <400> 32 Lys Arg Lys Thr Trp Asp Asn Asn Phe Ile Tyr Gln Ile Leu Asn Asp 1 5 10 15 Ser Asp Ser Arg Ala Asp Gly Thr Lys Pro Phe Ile Pro Ala Phe Asp 20 25 30 Ile Ser Lys Asn Glu Ile Val Glu Ala Ile Ile Asp Ser Phe Thr Ser 35 40 45 Lys Asn Ile Phe Trp Leu Pro Lys Asn Ile Glu Leu Gln Lys Val Asp 50 55 60 Asn Lys Asn Ile Phe Ala Ile Asp Thr Ser Lys Trp Phe Glu Val Glu 65 70 75 80 Thr Pro Ser Asp Leu Arg Asp Ile Gly Ile Ala Thr Ile Gln Tyr Lys 85 90 95 Ile Asp Asn Asn Ser Arg Pro Lys Val Arg Val Lys Leu Asp Tyr Val 100 105 110 Ile Asp Asp Asp Ser Lys Ile Asn Tyr Phe Met Asn His Ser Leu Leu 115 120 125 Lys Ser Arg Tyr Pro Asp Lys Val Leu Glu Ile Leu Lys Gln Ser Thr 130 135 140 Ile Ile Glu Phe Glu Ser Ser Gly Phe Asn Lys Thr Ile Lys Glu Met 145 150 155 160 Leu Gly Met Lys Leu Ala Gly Ile Tyr Asn Glu Thr Ser Asn Asn 165 170 175 <210> 33 <211> 145 <212> PRT <213> Lactobacillus buchneri <400> 33 Lys Gln Leu Val Leu Ser Asp Lys Ala Met Gln Val Leu Ser Lys Asp 1 5 10 15 Asp Lys Leu Lys Asn Gln Asp Glu Asn Gln Asn Leu Ile Asp Val Tyr 20 25 30 Asp Glu Ile Leu Glu Lys Val Asp Gln Tyr Phe Glu Leu Tyr Asp Ile 35 40 45 Asn Lys Phe Arg Gln Lys Leu His Asp Gly Arg Lys Lys Phe Ile Glu 50 55 60 Leu Pro Val Asp Asn Asp Phe Asn Gly Lys Lys Leu Ile Ser Tyr Gly 65 70 75 80 Lys Arg Ala Thr Ile Ile Ser Ile Leu Asn Gly Leu His Ala Asn Ala 85 90 95 Thr Met Ser Asn Leu Lys Tyr Leu Gly Ile Ser Ser Pro Phe Gly Met 100 105 110 Leu Gln Val Pro Asn Gly Ile Ile Leu Ser Pro Ala Ser Arg Ile Cys 115 120 125 Tyr Gln Ser Pro Thr Gly Leu Phe Glu Arg Lys Val Lys Leu Ser Asp 130 135 140 Leu 145 <210> 34 <211> 155 <212> PRT <213> Trepanoma denticola <400> 34 Ser Gln Arg Glu Lys Ile Gly Lys Thr Ile Ser Pro Tyr Glu Asp Leu 1 5 10 15 Ser Phe Arg Ser Tyr Ile Lys Glu Asn Leu Trp Lys Lys Thr Lys Asn 20 25 30 Asp Glu Ile Gly Glu Lys Glu Phe Tyr Asp Leu Leu Gln Lys Lys Asn 35 40 45 Leu Glu Ile Tyr Asp Met Leu Leu Thr Lys His Lys Asp Thr Ile Tyr 50 55 60 Lys Lys Arg Pro Asn Ser Ala Thr Ile Asp Ile Leu Val Lys Gly Lys 65 70 75 80 Glu Lys Phe Lys Ser Leu Ile Ile Glu Asn Gln Phe Glu Val Ile Leu 85 90 95 Glu Ile Leu Lys Leu Phe Ser Ala Thr Arg Asn Val Ser Asp Leu Gln 100 105 110 His Ile Gly Gly Ser Lys Tyr Ser Gly Val Ala Lys Ile Gly Asn Lys 115 120 125 Ile Ser Ser Leu Asp Asn Cys Ile Leu Ile Tyr Gln Ser Ile Thr Gly 130 135 140 Ile Phe Glu Lys Arg Ile Asp Leu Leu Lys Val 145 150 155 <210> 35 <211> 150 <212> PRT <213> Streptococcus thermophilus <400> 35 Asn Lys Thr Thr Gly Lys Tyr Glu Ile Leu Gly Leu Lys Tyr Ala Asp 1 5 10 15 Leu Gln Phe Glu Lys Gly Thr Gly Thr Tyr Lys Ile Ser Gln Glu Lys 20 25 30 Tyr Asn Asp Ile Lys Lys Lys Glu Gly Val Asp Ser Asp Ser Glu Phe 35 40 45 Lys Phe Thr Leu Tyr Lys Asn Asp Leu Leu Leu Val Lys Asp Thr Glu 50 55 60 Thr Lys Glu Gln Gln Leu Phe Arg Phe Leu Ser Arg Thr Met Pro Lys 65 70 75 80 Gln Lys His Tyr Val Glu Leu Lys Pro Tyr Asp Lys Gln Lys Phe Glu 85 90 95 Gly Gly Glu Ala Leu Ile Lys Val Leu Gly Asn Val Ala Asn Ser Gly 100 105 110 Gln Cys Lys Lys Gly Leu Gly Lys Ser Asn Ile Ser Ile Tyr Lys Val 115 120 125 Arg Thr Asp Val Leu Gly Asn Gln His Ile Ile Lys Asn Glu Gly Asp 130 135 140 Lys Pro Lys Leu Asp Phe 145 150 <210> 36 <211> 128 <212> PRT <213> Neisseria meningitidis <400> 36 Lys Gly Asp Lys Tyr Tyr Leu Val Pro Ile Tyr Ser Trp Gln Val Ala 1 5 10 15 Lys Gly Ile Leu Pro Asp Arg Ala Val Val Gln Gly Lys Asp Glu Glu 20 25 30 Asp Trp Gln Leu Ile Asp Asp Ser Phe Asn Phe Lys Phe Ser Leu His 35 40 45 Pro Asn Asp Leu Val Glu Val Ile Thr Lys Lys Ala Arg Met Phe Gly 50 55 60 Tyr Phe Ala Ser Cys His Arg Gly Thr Gly Asn Ile Asn Ile Arg Ile 65 70 75 80 His Asp Leu Asp His Lys Ile Gly Lys Asn Gly Ile Leu Glu Gly Ile 85 90 95 Gly Val Lys Thr Ala Leu Ser Phe Gln Lys Tyr Gln Ile Asp Glu Leu 100 105 110 Gly Lys Glu Ile Arg Pro Cys Arg Leu Lys Lys Arg Pro Pro Val Arg 115 120 125 <210> 37 <211> 127 <212> PRT <213> Pasteurella multocida <400> 37 Lys Asn Asn Lys Phe Phe Leu Val Pro Ile Tyr Thr Trp Gln Val Ala 1 5 10 15 Lys Gly Ile Leu Pro Asn Lys Ala Ile Val Ala His Lys Asn Glu Asp 20 25 30 Glu Trp Glu Glu Met Asp Glu Gly Ala Lys Phe Lys Phe Ser Leu Phe 35 40 45 Pro Asn Asp Leu Val Glu Leu Lys Thr Lys Lys Glu Tyr Phe Phe Gly 50 55 60 Tyr Tyr Ile Gly Leu Asp Arg Ala Thr Gly Asn Ile Ser Leu Lys Glu 65 70 75 80 His Asp Gly Glu Ile Ser Lys Gly Lys Asp Gly Val Tyr Arg Val Gly 85 90 95 Val Lys Leu Ala Leu Ser Phe Glu Lys Tyr Gln Val Asp Glu Leu Gly 100 105 110 Lys Asn Arg Gln Ile Cys Arg Pro Gln Gln Arg Gln Pro Val Arg 115 120 125 <210> 38 <211> 141 <212> PRT <213> Campylobacter jejuni <400> 38 Phe Tyr Ala Val Pro Ile Tyr Thr Met Asp Phe Ala Leu Lys Val Leu 1 5 10 15 Pro Asn Lys Ala Val Ala Arg Ser Lys Lys Gly Glu Ile Lys Asp Trp 20 25 30 Ile Leu Met Asp Glu Asn Tyr Glu Phe Cys Phe Ser Leu Tyr Lys Asp 35 40 45 Ser Leu Ile Leu Ile Gln Thr Lys Asp Met Gln Glu Pro Glu Phe Val 50 55 60 Tyr Tyr Asn Ala Phe Thr Ser Ser Thr Val Ser Leu Ile Val Ser Lys 65 70 75 80 His Asp Asn Lys Phe Glu Thr Leu Ser Lys Asn Gln Lys Ile Leu Phe 85 90 95 Lys Asn Ala Asn Glu Lys Glu Val Ile Ala Lys Ser Ile Gly Ile Gln 100 105 110 Asn Leu Lys Val Phe Glu Lys Tyr Ile Val Ser Ala Leu Gly Glu Val 115 120 125 Thr Lys Ala Glu Phe Arg Gln Arg Glu Asp Phe Lys Lys 130 135 140 <210> 39 <211> 148 <212> PRT <213> Actinomyces naeslundii <400> 39 Gln Arg His Gly Asp Leu Phe Ser Ala Val Ile Pro Pro Gln Ser Ile 1 5 10 15 Ser Met Arg Cys Ala Glu Pro Lys Leu Arg Lys Ala Ile Thr Thr Gly 20 25 30 Asn Ala Thr Tyr Leu Gly Trp Val Val Val Gly Asp Glu Leu Glu Ile 35 40 45 Asn Val Asp Ser Phe Thr Lys Tyr Ala Ile Gly Arg Phe Leu Glu Asp 50 55 60 Phe Pro Asn Thr Thr Arg Trp Arg Ile Cys Gly Tyr Asp Thr Asn Ser 65 70 75 80 Lys Leu Thr Leu Lys Pro Ile Val Leu Ala Ala Glu Gly Leu Glu Asn 85 90 95 Pro Ser Ser Ala Val Asn Glu Ile Val Glu Leu Lys Gly Trp Arg Val 100 105 110 Ala Ile Asn Val Leu Thr Lys Val His Pro Thr Val Val Arg Arg Asp 115 120 125 Ala Leu Gly Arg Pro Arg Tyr Ser Ser Arg Ser Asn Leu Pro Thr Ser 130 135 140 Trp Thr Ile Glu 145 <210> 40 <211> 135 <212> PRT <213> Staphylococcus aureus <400> 40 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 1 5 10 15 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 20 25 30 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 35 40 45 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 50 55 60 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 65 70 75 80 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 85 90 95 Arg Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 100 105 110 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 115 120 125 Pro Gln Ile Ile Lys Lys Gly 130 135 <210> 41 <211> 6 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (1)..(2) <223> a, c, t, g, unknown or other <400> 41 nnaagt 6 <210> 42 <211> 6 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (1)..(2) <223> a, c, t, g, unknown or other <400> 42 nnaggt 6 <210> 43 <211> 6 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (1)..(2) <223> a, c, t, g, unknown or other <400> 43 nnarrt 6 <210> 44 <211> 6 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (1)..(2) <223> a, c, t, g, unknown or other <400> 44 nnhrrt 6 <210> 45 <211> 6 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (1)..(2) <223> a, c, t, g, unknown or other <400> 45 nnrrrt 6 <210> 46 <211> 6 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (1)..(2) <223> a, c, t, g, unknown or other <400> 46 nngrrt 6 <210> 47 <211> 6 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (1)..(2) <223> a, c, t, g, unknown or other <400> 47 nncrrt 6 <210> 48 <211> 6 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (1)..(2) <223> a, c, t, g, unknown or other <400> 48 nntrrt 6 <210> 49 <211> 6 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (1)..(2) <223> a, c, t, g, unknown or other <220> <221> modified_base <222> (6)..(6) <223> a, c, t, g, unknown or other <400> 49 nngrrn 6 <210> 50 <400> 50 000 <210> 51 <400> 51 000 <210> 52 <400> 52 000 <210> 53 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 53 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Arg Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Lys Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro His Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Asn Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 54 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 54 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Glu Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Met Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Met Ala Ser Phe Tyr Lys Asn Asp Leu 305 310 315 320 Ile Lys Phe Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro His Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 55 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 55 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Ile Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asn Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ser Ser Phe Tyr Ser Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro His Ile Ile Lys Arg 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 56 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 56 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Val Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro His Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Glu Ile Ile Lys 385 390 395 400 Lys Gly <210> 57 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 57 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Arg Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro His Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 58 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 58 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Lys Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Phe Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asn Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Gly 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro His Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 59 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 59 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Lys Asp Lys Arg Pro Pro His Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Ile Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 60 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 60 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 His Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro His Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Asn Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 61 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 61 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Asn Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro His Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys Arg Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 62 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 62 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Leu Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Arg Asn Leu Asp Val Ile Lys Lys Glu Asn His 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 63 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 63 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Lys Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Thr Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Val Lys 385 390 395 400 Lys Gly <210> 64 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 64 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Arg Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Tyr Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Thr Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys Gln Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 65 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 65 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Leu Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 66 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 66 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Ile Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Met Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Ile Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 67 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 67 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Arg Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Val Ile Lys 385 390 395 400 Lys Gly <210> 68 <211> 400 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 68 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Arg Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Asp Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Ile Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Arg Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Tyr Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 <210> 69 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 69 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Arg Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Thr Lys 385 390 395 400 Lys Gly <210> 70 <211> 399 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 70 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Asn Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Gln Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Asn Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Asn Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile 385 390 395 <210> 71 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 71 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Tyr Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Ile Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Val Lys 385 390 395 400 Lys Gly <210> 72 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 72 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 73 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 73 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Lys Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 74 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 74 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Leu Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Met Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr His Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro His Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 75 <211> 396 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 75 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Ile Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Tyr Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Ser Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro 385 390 395 <210> 76 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 76 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Asn Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 77 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 77 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Leu Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Lys Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Cys Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 78 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 78 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Lys Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Gly Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Asp Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Leu Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Val Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 79 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 79 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Ile Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Lys Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Asn Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 80 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 80 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Ile Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 81 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 81 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Gln 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Tyr Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Lys Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro His Ile Ile Lys 385 390 395 400 Lys Gly <210> 82 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 82 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Ile Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Arg Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 83 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 83 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Phe Glu Asn Met Asn Val Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 84 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 84 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys His 115 120 125 Asn Arg Glu Leu Val Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Thr Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 85 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 85 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Met Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Glu 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Arg Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 86 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 86 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Val Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Asn Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Tyr Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Arg Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Arg Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 87 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 87 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Asn Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Ile Asn Gly Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Thr Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 88 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 88 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Asn Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Glu Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Ile Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Gly Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Ile Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Asn Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 89 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 89 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Val Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Ile Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Val Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Ile 385 390 395 400 Lys Gly <210> 90 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 90 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Gly 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 91 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 91 Ala Thr Arg Gly Leu Met Asn Leu Leu Lys Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ser Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys His 115 120 125 Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Ile Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Thr Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Pro Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 92 <211> 396 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 92 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Glu Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Ser Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Tyr Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro 385 390 395 <210> 93 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 93 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro Tyr Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Arg Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 94 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 94 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Asn Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Arg Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Phe Lys Tyr Ser His Met Val Asp Lys Lys Pro 115 120 125 Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Ile Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 95 <211> 396 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 95 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Ile Arg Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro 385 390 395 <210> 96 <211> 396 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 96 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Val Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Ile Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro 385 390 395 <210> 97 <211> 396 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 97 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro 385 390 395 <210> 98 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 98 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Met Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asp Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro His Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Gln Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 99 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 99 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Gly Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Arg Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Ser Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Thr Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 100 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 100 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Tyr Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Thr Asn Lys Ser Pro Gly Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala Tyr Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Asn Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Glu Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro His Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 101 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 101 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Phe Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Asp Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Thr Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 102 <211> 400 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 102 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Thr Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys His Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asp Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 <210> 103 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 103 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Asn Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Tyr Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 104 <211> 402 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 104 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 1 5 10 15 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 20 25 30 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 35 40 45 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 50 55 60 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 65 70 75 80 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 85 90 95 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 100 105 110 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 115 120 125 Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 130 135 140 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 145 150 155 160 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 165 170 175 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 180 185 190 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 195 200 205 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 210 215 220 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 225 230 235 240 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 245 250 255 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 260 265 270 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 275 280 285 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 290 295 300 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 305 310 315 320 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 325 330 335 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 340 345 350 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Gln Ile Ile Lys Thr 355 360 365 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 370 375 380 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 385 390 395 400 Lys Gly <210> 105 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 105 gggcacgggc agcttgcccg 20 <210> 106 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 106 gtcgccctcg aacttcacct 20 <210> 107 <211> 70 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 107 cgtaaggagc gcgaggcggc ggccgcggcg gcggaggctg caggactgag cgagcagatc 60 gtgtttgagg 70 <210> 108 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 108 cgtaaggagc gagcagatcg tgtttgagg 29 <210> 109 <211> 36 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 109 cgtaaggagc gcgaggcgag cagatcgtgt ttgagg 36 <210> 110 <211> 41 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 110 cgtaaggagc gcgaggctga gcgagcagat cgtgtttgag g 41 <210> 111 <211> 42 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 111 cgtaaggagc gcgaggcggc ggcgagcaga tcgtgtttga gg 42 <210> 112 <211> 54 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 112 cgtaaggagc gcgaggcggc ggccgcagat cgagcgagca gatcgtgttt gagg 54 <210> 113 <211> 55 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 113 cgtaaggagc gcgaggcggc ggccgcggcg gctagcgagc agatcgtgtt tgagg 55 <210> 114 <211> 55 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 114 cgtaaggagc gcgaggcggc ggccgcggcg gcgggcgagc agatcgtgtt tgagg 55 <210> 115 <211> 56 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 115 cgtaaggagc gcgaggcggc ggccgcggcg gctgagcgag cagatcgtgt ttgagg 56 <210> 116 <211> 51 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 116 cgtaaggagc gcgaggcagc ggccgcggcg gcgagcagat cgtgtttgag g 51 <210> 117 <211> 57 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 117 cgtaaggagc gcagagagcg taaggagcgc gaggcggcga gcagatcgtg tttgagg 57 <210> 118 <211> 62 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 118 cgtaaggagc gcgaggcggc ggccgcggcg gcggaggctg agcgagcaga tcgtgtttga 60 gg 62 <210> 119 <211> 69 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 119 cgtaaggagc gcgaggcggc ggccgcggcg gcggaggctg cagactgagc gagcagatcg 60 tgtttgagg 69 <210> 120 <211> 70 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 120 cgtaaggagc gcgaggcggc ggccgcggcg gcggaggctg agcgagactg agcgagcaga 60 tcgtgtttga 70 <210> 121 <211> 70 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 121 cgtaaggagc gcgaggcggc ggccgcggcg gcggaggctg cagcgagcag agcgagcaga 60 tcgtgtttga 70 <210> 122 <211> 61 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 122 tgtcgggaac ctctccaggg atgttacgga ggccctcatc ctgcaagtgt tctctcagat 60 c 61 <210> 123 <211> 49 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 123 tgtcgggtat gttacggagg ccctcatcct gcaagtgttc tctcagatc 49 <210> 124 <211> 53 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 124 tgtcgggaac ctctgttacg gaggccctca tcctgcaagt gttctctcag atc 53 <210> 125 <211> 56 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 125 tgtcgggaac ctctcctgtt acggaggccc tcatcctgca agtgttctct cagatc 56 <210> 126 <211> 57 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 126 tgtcgggaac ctctccatgt tacggaggcc ctcatcctgc aagtgttctc tcagatc 57 <210> 127 <211> 60 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 127 tgtcgggaac ctctccggga tgttacggag gcccttatcc tgcaagtgtt ctctcagatc 60 <210> 128 <211> 60 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 128 tgtcgggaac ctctccatga tgttacggag gccctcatcc tgcaagtgtt ctctcagatc 60 <210> 129 <211> 61 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 129 tgtcgggaac ctctccaggg acgttacgga ggccctcatc ctgcaagtgt tctctcagat 60 c 61 <210> 130 <211> 61 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 130 tgtcgggaac ctctgaaccg gatgttacgg aggccctcat cctgcaagtg ttctctcaga 60 t 61 <210> 131 <211> 61 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 131 tgtcgggaac ctctcgttac ggagatgtta cggaggccct catcctgcaa gtgttctctc 60 a 61 <210> 132 <211> 61 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 132 tgtcgggaac ctctccatgt tacggatgtt acggaggccc tcatcctgca agtgttctct 60 c 61 <210> 133 <211> 61 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 133 tgtcgggaac ctctccatgt tgtggatgtt acggaggccc tcatcctgca agtgttctct 60 c 61 <210> 134 <211> 61 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 134 tgtcgggaac ctctccattt gagagggaat tatttataaa ataaataatt acggaggccc 60 t 61 <210> 135 <211> 61 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 135 catggcgacc gggggcggaa ctactgctct ccaaccagag gcgagaatcg gggggcggac 60 g 61 <210> 136 <211> 55 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 136 catggcgacc gggggcggaa ctactgcacc agaggcgaga atcggggggc ggacg 55 <210> 137 <211> 56 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 137 catggcgacc gggggcggaa ctactgctct cagaggcgag aatcgggggg cggacg 56 <210> 138 <211> 57 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 138 catggcgacc gggggcggaa ctactgctct ccagaggcga gaatcggggg gcggacg 57 <210> 139 <211> 57 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 139 catggcgacc gggggcggaa ctactgctcg ccagaggcga gaatcggggg gcggacg 57 <210> 140 <211> 61 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 140 catggcgacc gggggcggaa ctactgctct ccagaggcca gaggcgagaa tcggggggcg 60 g 61 <210> 141 <211> 61 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 141 catggcgacc gggggcggag ctactgctct ctactgctct ctcaccagag gcgagaatcg 60 g 61 <210> 142 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (21)..(21) <223> a, c, t, g, unknown or other <220> <221> modified_base <222> (24)..(24) <223> a, c, t, g, unknown or other <400> 142 gccacgaagc aggccaatgg ngan 24 <210> 143 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (21)..(21) <223> a, c, t, g, unknown or other <220> <221> modified_base <222> (24)..(24) <223> a, c, t, g, unknown or other <400> 143 gaatcccttc tgcagcacct ngan 24 <210> 144 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (21)..(21) <223> a, c, t, g, unknown or other <220> <221> modified_base <222> (24)..(24) <223> a, c, t, g, unknown or other <400> 144 gcggcggctg cacaaccagt ngan 24 <210> 145 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (21)..(21) <223> a, c, t, g, unknown or other <220> <221> modified_base <222> (24)..(24) <223> a, c, t, g, unknown or other <400> 145 ggttgtgcag ccgccgctcc ngan 24 <210> 146 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (21)..(21) <223> a, c, t, g, unknown or other <220> <221> modified_base <222> (24)..(24) <223> a, c, t, g, unknown or other <400> 146 ggtgcatttt caggaggaag ngan 24 <210> 147 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (21)..(21) <223> a, c, t, g, unknown or other <220> <221> modified_base <222> (24)..(24) <223> a, c, t, g, unknown or other <400> 147 gagatgtagg gctagagggg ngan 24 <210> 148 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (21)..(21) <223> a, c, t, g, unknown or other <220> <221> modified_base <222> (24)..(24) <223> a, c, t, g, unknown or other <400> 148 gcgagcagcg tcttcgagag ngan 24 <210> 149 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (21)..(21) <223> a, c, t, g, unknown or other <220> <221> modified_base <222> (24)..(24) <223> a, c, t, g, unknown or other <400> 149 gtgcggcaag agcttcagcc ngan 24 <210> 150 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (21)..(21) <223> a, c, t, g, unknown or other <400> 150 gcagaaggga ttccatgagg ngcg 24 <210> 151 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (20)..(20) <223> a, c, t, g, unknown or other <400> 151 gaagggattc catgaggtgn gcg 23 <210> 152 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (20)..(20) <223> a, c, t, g, unknown or other <400> 152 gggtgcattt tcaggaggan gcg 23 <210> 153 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (21)..(21) <223> a, c, t, g, unknown or other <400> 153 gcagacggca gtcactaggg ngcg 24 <210> 154 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (21)..(21) <223> a, c, t, g, unknown or other <400> 154 gctgggtgaa tggagcgagc ngcg 24 <210> 155 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 155 gagtccgagc agaagaagaa ggg 23 <210> 156 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 156 gtgcggcaag agcttcagcc ggg 23 <210> 157 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 157 ggtgagtgag tgtgtgcgtg tgg 23 <210> 158 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (22)..(23) <223> a, c, t, g, unknown or other <400> 158 gcaaccacaa acccacgagg gnngrrt 27 <210> 159 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (22)..(23) <223> a, c, t, g, unknown or other <400> 159 gggtgagtga gtgtgtgcgt gnngrrt 27 <210> 160 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (23)..(25) <223> a, c, t, g, unknown or other <400> 160 gtgtggttcc agaaccggag gannnrrt 28 <210> 161 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (22)..(24) <223> a, c, t, g, unknown or other <400> 161 gctcagcctg agtgttgagg cnnnrrt 27 <210> 162 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (22)..(24) <223> a, c, t, g, unknown or other <400> 162 ggctctccga ggagaaggcc annnrrt 27 <210> 163 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (23)..(25) <223> a, c, t, g, unknown or other <400> 163 gcgcccactg caaggcccgg cgnnnrrt 28 <210> 164 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (22)..(24) <223> a, c, t, g, unknown or other <400> 164 ggggtcccag gtgctgacgt annnrrt 27 <210> 165 <211> 483 <212> PRT <213> Streptococcus pyogenes <400> 165 Leu Leu Asn Ala Lys Leu Ile Thr Gln Arg Lys Phe Asp Asn Leu Thr 1 5 10 15 Lys Ala Glu Arg Gly Gly Leu Ser Glu Leu Asp Lys Ala Gly Phe Ile 20 25 30 Lys Arg Gln Leu Val Glu Thr Arg Gln Ile Thr Lys His Val Ala Gln 35 40 45 Ile Leu Asp Ser Arg Met Asn Thr Lys Tyr Asp Glu Asn Asp Lys Leu 50 55 60 Ile Arg Glu Val Lys Val Ile Thr Leu Lys Ser Lys Leu Val Ser Asp 65 70 75 80 Phe Arg Lys Asp Phe Gln Phe Tyr Lys Val Arg Glu Ile Asn Asn Tyr 85 90 95 His His Ala His Asp Ala Tyr Leu Asn Ala Val Val Gly Thr Ala Leu 100 105 110 Ile Lys Lys Tyr Pro Lys Leu Glu Ser Glu Phe Val Tyr Gly Asp Tyr 115 120 125 Lys Val Tyr Asp Val Arg Lys Met Ile Ala Lys Ser Glu Gln Glu Ile 130 135 140 Gly Lys Ala Thr Ala Lys Tyr Phe Phe Tyr Ser Asn Ile Met Asn Phe 145 150 155 160 Phe Lys Thr Glu Ile Thr Leu Ala Asn Gly Glu Ile Arg Lys Arg Pro 165 170 175 Leu Ile Glu Thr Asn Gly Glu Thr Gly Glu Ile Val Trp Asp Lys Gly 180 185 190 Arg Asp Phe Ala Thr Val Arg Lys Val Leu Ser Met Pro Gln Val Asn 195 200 205 Ile Val Lys Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser 210 215 220 Ile Leu Pro Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp 225 230 235 240 Trp Asp Pro Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val Ala Tyr 245 250 255 Ser Val Leu Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu 260 265 270 Lys Ser Val Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser 275 280 285 Phe Glu Lys Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu 290 295 300 Val Lys Lys Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu 305 310 315 320 Leu Glu Asn Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln 325 330 335 Lys Gly Asn Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr 340 345 350 Leu Ala Ser His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu 355 360 365 Gln Lys Gln Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile 370 375 380 Ile Glu Gln Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala 385 390 395 400 Asn Leu Asp Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro 405 410 415 Ile Arg Glu Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn 420 425 430 Leu Gly Ala Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg 435 440 445 Lys Arg Tyr Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His 450 455 460 Gln Ser Ile Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu 465 470 475 480 Gly Gly Asp <210> 166 <211> 460 <212> PRT <213> Streptococcus mutans <400> 166 Leu Leu Ser Ala Lys Leu Ile Thr Gln Arg Lys Phe Asp Asn Leu Thr 1 5 10 15 Lys Ala Glu Arg Gly Gly Leu Thr Asp Asp Asp Lys Ala Gly Phe Ile 20 25 30 Lys Arg Gln Leu Val Glu Thr Arg Gln Ile Thr Lys His Val Ala Arg 35 40 45 Ile Leu Asp Glu Arg Phe Asn Thr Glu Thr Asp Glu Asn Asn Lys Lys 50 55 60 Ile Arg Gln Val Lys Ile Val Thr Leu Lys Ser Asn Leu Val Ser Asn 65 70 75 80 Phe Arg Lys Glu Phe Glu Leu Tyr Lys Val Arg Glu Ile Asn Asp Tyr 85 90 95 His His Ala His Asp Ala Tyr Leu Asn Ala Val Ile Gly Lys Ala Leu 100 105 110 Leu Gly Val Tyr Pro Gln Leu Glu Pro Glu Phe Val Tyr Gly Asp Tyr 115 120 125 Pro His Phe His Gly His Lys Glu Asn Lys Ala Thr Ala Lys Lys Phe 130 135 140 Phe Tyr Ser Asn Ile Met Asn Phe Phe Lys Lys Asp Asp Val Arg Thr 145 150 155 160 Asp Lys Asn Gly Glu Ile Ile Trp Lys Lys Asp Glu His Ile Ser Asn 165 170 175 Ile Lys Lys Val Leu Ser Tyr Pro Gln Val Asn Ile Val Lys Lys Val 180 185 190 Glu Glu Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro Lys Gly 195 200 205 Asn Ser Asp Lys Leu Ile Pro Arg Lys Thr Lys Lys Phe Tyr Trp Asp 210 215 220 Thr Lys Lys Tyr Gly Gly Phe Asp Ser Pro Ile Val Ala Tyr Ser Ile 225 230 235 240 Leu Val Ile Ala Asp Ile Glu Lys Gly Lys Ser Lys Lys Leu Lys Thr 245 250 255 Val Lys Ala Leu Val Gly Val Thr Ile Met Glu Lys Met Thr Phe Glu 260 265 270 Arg Asp Pro Val Ala Phe Leu Glu Arg Lys Gly Tyr Arg Asn Val Gln 275 280 285 Glu Glu Asn Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Lys Leu Glu 290 295 300 Asn Gly Arg Lys Arg Leu Leu Ala Ser Ala Arg Glu Leu Gln Lys Gly 305 310 315 320 Asn Glu Ile Val Leu Pro Asn His Leu Gly Thr Leu Leu Tyr His Ala 325 330 335 Lys Asn Ile His Lys Val Asp Glu Pro Lys His Leu Asp Tyr Val Asp 340 345 350 Lys His Lys Asp Glu Phe Lys Glu Leu Leu Asp Val Val Ser Asn Phe 355 360 365 Ser Lys Lys Tyr Thr Leu Ala Glu Gly Asn Leu Glu Lys Ile Lys Glu 370 375 380 Leu Tyr Ala Gln Asn Asn Gly Glu Asp Leu Lys Glu Leu Ala Ser Ser 385 390 395 400 Phe Ile Asn Leu Leu Thr Phe Thr Ala Ile Gly Ala Pro Ala Thr Phe 405 410 415 Lys Phe Phe Asp Lys Asn Ile Asp Arg Lys Arg Tyr Thr Ser Thr Thr 420 425 430 Glu Ile Leu Asn Ala Thr Leu Ile His Gln Ser Ile Thr Gly Leu Tyr 435 440 445 Glu Thr Arg Ile Asp Leu Asn Lys Leu Gly Gly Asp 450 455 460 <210> 167 <211> 496 <212> PRT <213> Streptococcus thermophilus <400> 167 Leu Leu Lys Ser Lys Leu Ile Ser Gln Arg Lys Phe Asp Asn Leu Thr 1 5 10 15 Lys Ala Glu Arg Gly Gly Leu Leu Pro Glu Asp Lys Ala Gly Phe Ile 20 25 30 Gln Arg Gln Leu Val Glu Thr Arg Gln Ile Thr Lys His Val Ala Arg 35 40 45 Leu Leu Asp Glu Lys Phe Asn Asn Lys Lys Asp Glu Asn Asn Arg Ala 50 55 60 Val Arg Thr Val Lys Ile Ile Thr Leu Lys Ser Thr Leu Val Ser Gln 65 70 75 80 Phe Arg Lys Asp Phe Glu Leu Tyr Lys Val Arg Glu Ile Asn Asp Phe 85 90 95 His His Ala His Asp Ala Tyr Leu Asn Ala Val Ile Ala Ser Ala Leu 100 105 110 Leu Lys Lys Tyr Pro Lys Leu Glu Pro Glu Phe Val Tyr Gly Asp Tyr 115 120 125 Pro Lys Tyr Asn Ser Phe Arg Glu Arg Lys Ser Ala Thr Glu Lys Val 130 135 140 Tyr Phe Tyr Ser Asn Ile Met Asn Ile Phe Lys Lys Ser Ile Ser Leu 145 150 155 160 Ala Asp Gly Arg Val Ile Glu Arg Pro Leu Ile Glu Val Asn Glu Glu 165 170 175 Thr Gly Glu Ser Val Trp Asn Lys Glu Ser Asp Leu Ala Thr Val Arg 180 185 190 Arg Val Leu Ser Tyr Pro Gln Val Asn Val Val Lys Lys Val Glu Glu 195 200 205 Gln Asn His Gly Leu Asp Arg Gly Lys Pro Lys Gly Leu Phe Asn Ala 210 215 220 Asn Leu Ser Ser Lys Pro Lys Pro Asn Ser Asn Glu Asn Leu Val Gly 225 230 235 240 Ala Lys Glu Tyr Leu Asp Pro Lys Lys Tyr Gly Gly Tyr Ala Gly Ile 245 250 255 Ser Asn Ser Phe Ala Val Leu Val Lys Gly Thr Ile Glu Lys Gly Ala 260 265 270 Lys Lys Lys Ile Thr Asn Val Leu Glu Phe Gln Gly Ile Ser Ile Leu 275 280 285 Asp Arg Ile Asn Tyr Arg Lys Asp Lys Leu Asn Phe Leu Leu Glu Lys 290 295 300 Gly Tyr Lys Asp Ile Glu Leu Ile Ile Glu Leu Pro Lys Tyr Ser Leu 305 310 315 320 Phe Glu Leu Ser Asp Gly Ser Arg Arg Met Leu Ala Ser Ile Leu Ser 325 330 335 Thr Asn Asn Lys Arg Gly Glu Ile His Lys Gly Asn Gln Ile Phe Leu 340 345 350 Ser Gln Lys Phe Val Lys Leu Leu Tyr His Ala Lys Arg Ile Ser Asn 355 360 365 Thr Ile Asn Glu Asn His Arg Lys Tyr Val Glu Asn His Lys Lys Glu 370 375 380 Phe Glu Glu Leu Phe Tyr Tyr Ile Leu Glu Phe Asn Glu Asn Tyr Val 385 390 395 400 Gly Ala Lys Lys Asn Gly Lys Leu Leu Asn Ser Ala Phe Gln Ser Trp 405 410 415 Gln Asn His Ser Ile Asp Glu Leu Cys Ser Ser Phe Ile Gly Pro Thr 420 425 430 Gly Ser Glu Arg Lys Gly Leu Phe Glu Leu Thr Ser Arg Gly Ser Ala 435 440 445 Ala Asp Phe Glu Phe Leu Gly Val Lys Ile Pro Arg Tyr Arg Asp Tyr 450 455 460 Thr Pro Ser Ser Leu Leu Lys Asp Ala Thr Leu Ile His Gln Ser Val 465 470 475 480 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ala Lys Leu Gly Glu Gly 485 490 495 <210> 168 <211> 446 <212> PRT <213> Listeria innocua <400> 168 Leu Tyr Gln Gly Asn Leu Met Ser Lys Arg Lys Phe Asp Tyr Leu Thr 1 5 10 15 Lys Ala Glu Arg Gly Gly Leu Thr Glu Ala Asp Lys Ala Arg Phe Ile 20 25 30 His Arg Gln Leu Val Glu Thr Arg Gln Ile Thr Lys Asn Val Ala Asn 35 40 45 Ile Leu His Gln Arg Phe Asn Tyr Glu Lys Asp Asp His Gly Asn Thr 50 55 60 Met Lys Gln Val Arg Ile Val Thr Leu Lys Ser Ala Leu Val Ser Gln 65 70 75 80 Phe Arg Lys Gln Phe Gln Leu Tyr Lys Val Arg Asp Val Asn Asp Tyr 85 90 95 His His Ala His Asp Ala Tyr Leu Asn Gly Val Val Ala Asn Thr Leu 100 105 110 Leu Lys Val Tyr Pro Gln Leu Glu Pro Glu Phe Val Tyr Gly Asp Tyr 115 120 125 His Gln Phe Asp Trp Phe Lys Ala Asn Lys Ala Thr Ala Lys Lys Gln 130 135 140 Phe Tyr Thr Asn Ile Met Leu Phe Phe Ala Gln Lys Asp Arg Ile Ile 145 150 155 160 Asp Glu Asn Gly Glu Ile Leu Trp Asp Lys Lys Tyr Leu Asp Thr Val 165 170 175 Lys Lys Val Met Ser Tyr Arg Gln Met Asn Ile Val Lys Lys Thr Glu 180 185 190 Ile Gln Lys Gly Glu Phe Ser Lys Ala Thr Ile Lys Pro Lys Gly Asn 195 200 205 Ser Ser Lys Leu Ile Pro Arg Lys Thr Asn Trp Asp Pro Met Lys Tyr 210 215 220 Gly Gly Leu Asp Ser Pro Asn Met Ala Tyr Ala Val Val Ile Glu Tyr 225 230 235 240 Ala Lys Gly Lys Asn Lys Leu Val Phe Glu Lys Lys Ile Ile Arg Val 245 250 255 Thr Ile Met Glu Arg Lys Ala Phe Glu Lys Asp Glu Lys Ala Phe Leu 260 265 270 Glu Glu Gln Gly Tyr Arg Gln Pro Lys Val Leu Ala Lys Leu Pro Lys 275 280 285 Tyr Thr Leu Tyr Glu Cys Glu Glu Gly Arg Arg Arg Met Leu Ala Ser 290 295 300 Ala Asn Glu Ala Gln Lys Gly Asn Gln Gln Val Leu Pro Asn His Leu 305 310 315 320 Val Thr Leu Leu His His Ala Ala Asn Cys Glu Val Ser Asp Gly Lys 325 330 335 Ser Leu Asp Tyr Ile Glu Ser Asn Arg Glu Met Phe Ala Glu Leu Leu 340 345 350 Ala His Val Ser Glu Phe Ala Lys Arg Tyr Thr Leu Ala Glu Ala Asn 355 360 365 Leu Asn Lys Ile Asn Gln Leu Phe Glu Gln Asn Lys Glu Gly Asp Ile 370 375 380 Lys Ala Ile Ala Gln Ser Phe Val Asp Leu Met Ala Phe Asn Ala Met 385 390 395 400 Gly Ala Pro Ala Ser Phe Lys Phe Phe Glu Thr Thr Ile Glu Arg Lys 405 410 415 Arg Tyr Asn Asn Leu Lys Glu Leu Leu Asn Ser Thr Ile Ile Tyr Gln 420 425 430 Ser Ile Thr Gly Leu Tyr Glu Ser Arg Lys Arg Leu Asp Asp 435 440 445 <210> 169 <211> 470 <212> PRT <213> Trepanoma denticola <400> 169 Leu Ala Glu Asn His Leu Ile Ser Lys Arg Lys Leu Asn Asn Leu Thr 1 5 10 15 Thr Asp Pro Asp Lys Ile Gly Lys Phe Thr Ala Gln Gly Phe Ile His 20 25 30 Arg Gln Leu Val Glu Thr Ser Gln Val Ile Arg Leu Val Ala Asn Ile 35 40 45 Leu Gly Asn Glu Tyr Gly His Asp Gly Thr Thr Ile Ile Glu Val Thr 50 55 60 Ala Lys Met Asn His Gln Met Arg Lys Asp Phe Asp Leu Ile Lys Ile 65 70 75 80 Arg Asp Val Asn Asp Tyr His His Ala Met Asp Ala Tyr Leu Thr Ala 85 90 95 Tyr Val Gly Asp Tyr Leu Tyr Leu Arg Tyr Pro Lys Leu Arg Ser Tyr 100 105 110 Phe Val Tyr Gly Asp Phe Lys Lys Leu Lys Asp Gln Ser Leu Lys Ile 115 120 125 Arg Asn Phe Asn Phe Leu His Asp Leu Thr Asn Asp Glu Ala Gly Asp 130 135 140 Lys Ile Val Asp Gln Glu Thr Gly Glu Ile Ile Trp Asp Lys His Glu 145 150 155 160 Ser Val Lys Gln Leu Lys Lys Val Tyr His Tyr Lys Phe Met Leu Val 165 170 175 Ser Gln Glu Val Tyr Thr Arg Gln Asp Ala Leu Phe Asn Gln Thr Ile 180 185 190 Tyr Pro Ala Ser Asp Ala Asp Lys Arg Lys Leu Ile Pro Ile Lys Asn 195 200 205 Asn Lys Pro Val Asp Val Tyr Gly Gly Tyr Ser Gly Asn Val Asp Ala 210 215 220 Tyr Met Ala Ile Val Arg Ile His Gly Lys Lys Glu Asp Lys Tyr Lys 225 230 235 240 Val Val Gly Val Pro Met Arg Ala Val Ala Asp Leu Lys Lys Ala Glu 245 250 255 Ser Lys Gly Arg Asp Asn Tyr Leu Asn Ala Val His Glu Val Leu Lys 260 265 270 Pro Gln Phe Thr Lys Lys Lys Lys Asp Arg Lys Thr Gly Glu Ile Thr 275 280 285 Glu Met Met Asp Asp Phe Asp Val Leu Leu Gly Lys Val Tyr Tyr Arg 290 295 300 Gln Leu Ile Val Asp Gly Asn Lys Lys Phe Met Leu Gly Ser Ser Thr 305 310 315 320 Tyr Gln Tyr Asn Ala Lys Gln Leu Val Leu Ser Asp Lys Ala Met Gln 325 330 335 Val Leu Ser Lys Asp Asp Lys Leu Lys Asn Gln Asp Glu Asn Gln Asn 340 345 350 Leu Ile Asp Val Tyr Asp Glu Ile Leu Glu Lys Val Asp Gln Tyr Phe 355 360 365 Glu Leu Tyr Asp Ile Asn Lys Phe Arg Gln Lys Leu His Asp Gly Arg 370 375 380 Lys Lys Phe Ile Glu Leu Pro Val Asp Asn Asp Phe Asn Gly Lys Lys 385 390 395 400 Leu Ile Ser Tyr Gly Lys Arg Ala Thr Ile Ile Ser Ile Leu Asn Gly 405 410 415 Leu His Ala Asn Ala Thr Met Ser Asn Leu Lys Tyr Leu Gly Ile Ser 420 425 430 Ser Pro Phe Gly Met Leu Gln Val Pro Asn Gly Ile Ile Leu Ser Pro 435 440 445 Ala Ser Arg Ile Cys Tyr Gln Ser Pro Thr Gly Leu Phe Glu Arg Lys 450 455 460 Val Lys Leu Ser Asp Leu 465 470 <210> 170 <211> 470 <212> PRT <213> Lactobacillus buchneri <400> 170 Leu Gln Arg Asn Asn Phe Ile Ser Leu Glu Lys Leu Asn Arg Leu Thr 1 5 10 15 Arg Ala Thr Pro Ile Ser Asp Asp Glu Thr Ala Lys Phe Ile Ala Arg 20 25 30 Gln Leu Val Glu Thr Arg Gln Ala Thr Lys Val Ala Ala Lys Val Leu 35 40 45 Glu Lys Met Phe Pro Glu Thr Lys Ile Val Tyr Ser Lys Ala Glu Thr 50 55 60 Val Ser Met Phe Arg Asn Lys Phe Asp Ile Val Lys Cys Arg Glu Ile 65 70 75 80 Asn Asp Phe His His Ala His Asp Ala Tyr Leu Asn Ile Val Val Gly 85 90 95 Asn Val Tyr Asn Thr Lys Phe Thr Asn Asn Pro Trp Asn Phe Ile Lys 100 105 110 Glu Lys Arg Asp Asn Pro Lys Ile Ala Asp Thr Tyr Asn Tyr Tyr Lys 115 120 125 Val Phe Asp Tyr Asp Val Lys Arg Asn Asn Ile Thr Ala Trp Glu Lys 130 135 140 Gly Lys Thr Ile Ile Thr Val Lys Asp Met Leu Lys Arg Asn Thr Pro 145 150 155 160 Ile Tyr Thr Arg Gln Ala Ala Cys Lys Lys Gly Glu Leu Phe Asn Gln 165 170 175 Thr Ile Met Lys Lys Gly Leu Gly Gln His Pro Leu Lys Lys Glu Gly 180 185 190 Pro Phe Ser Asn Ile Ser Lys Tyr Gly Gly Tyr Asn Lys Val Ser Ala 195 200 205 Ala Tyr Tyr Thr Leu Ile Glu Tyr Glu Glu Lys Gly Asn Lys Ile Arg 210 215 220 Ser Leu Glu Thr Ile Pro Leu Tyr Leu Val Lys Asp Ile Gln Lys Asp 225 230 235 240 Gln Asp Val Leu Lys Ser Tyr Leu Thr Asp Leu Leu Gly Lys Lys Glu 245 250 255 Phe Lys Ile Leu Val Pro Lys Ile Lys Ile Asn Ser Leu Leu Lys Ile 260 265 270 Asn Gly Phe Pro Cys His Ile Thr Gly Lys Thr Asn Asp Ser Phe Leu 275 280 285 Leu Arg Pro Ala Val Gln Phe Cys Cys Ser Asn Asn Glu Val Leu Tyr 290 295 300 Phe Lys Lys Ile Ile Arg Phe Ser Glu Ile Arg Ser Gln Arg Glu Lys 305 310 315 320 Ile Gly Lys Thr Ile Ser Pro Tyr Glu Asp Leu Ser Phe Arg Ser Tyr 325 330 335 Ile Lys Glu Asn Leu Trp Lys Lys Thr Lys Asn Asp Glu Ile Gly Glu 340 345 350 Lys Glu Phe Tyr Asp Leu Leu Gln Lys Lys Asn Leu Glu Ile Tyr Asp 355 360 365 Met Leu Leu Thr Lys His Lys Asp Thr Ile Tyr Lys Lys Arg Pro Asn 370 375 380 Ser Ala Thr Ile Asp Ile Leu Val Lys Gly Lys Glu Lys Phe Lys Ser 385 390 395 400 Leu Ile Ile Glu Asn Gln Phe Glu Val Ile Leu Glu Ile Leu Lys Leu 405 410 415 Phe Ser Ala Thr Arg Asn Val Ser Asp Leu Gln His Ile Gly Gly Ser 420 425 430 Lys Tyr Ser Gly Val Ala Lys Ile Gly Asn Lys Ile Ser Ser Leu Asp 435 440 445 Asn Cys Ile Leu Ile Tyr Gln Ser Ile Thr Gly Ile Phe Glu Lys Arg 450 455 460 Ile Asp Leu Leu Lys Val 465 470 <210> 171 <211> 430 <212> PRT <213> Pasteurella multocida <400> 171 Phe Val Ala Leu Val Leu Gly Ser Gln Cys Ser Ala Ala Lys Lys Gln 1 5 10 15 Arg Leu Leu Thr Gln Val Ile Asp Asp Asn Lys Phe Ile Asp Arg Asn 20 25 30 Leu Asn Asp Thr Arg Tyr Ile Ala Arg Phe Leu Ser Asn Tyr Ile Gln 35 40 45 Glu Asn Leu Leu Leu Val Gly Lys Asn Lys Lys Asn Val Phe Thr Pro 50 55 60 Asn Gly Gln Ile Thr Ala Leu Leu Arg Ser Arg Trp Gly Leu Ile Lys 65 70 75 80 Ala Arg Glu Asn Asn Asn Arg His His Ala Leu Asp Ala Ile Val Val 85 90 95 Ala Cys Ala Thr Pro Ser Met Gln Gln Lys Ile Thr Arg Phe Ile Arg 100 105 110 Phe Lys Glu Val His Pro Tyr Lys Ile Glu Asn Arg Tyr Glu Met Val 115 120 125 Asp Gln Glu Ser Gly Glu Ile Ile Ser Pro His Phe Pro Glu Pro Trp 130 135 140 Ala Tyr Phe Arg Gln Glu Val Asn Ile Arg Val Phe Asp Asn His Pro 145 150 155 160 Asp Thr Val Leu Lys Glu Met Leu Pro Asp Arg Pro Gln Ala Asn His 165 170 175 Gln Phe Val Gln Pro Leu Phe Val Ser Arg Ala Pro Thr Arg Lys Met 180 185 190 Ser Gly Gln Gly His Met Glu Thr Ile Lys Ser Ala Lys Arg Leu Ala 195 200 205 Glu Gly Ile Ser Val Leu Arg Ile Pro Leu Thr Gln Leu Lys Pro Asn 210 215 220 Leu Leu Glu Asn Met Val Asn Lys Glu Arg Glu Pro Ala Leu Tyr Ala 225 230 235 240 Gly Leu Lys Ala Arg Leu Ala Glu Phe Asn Gln Asp Pro Ala Lys Ala 245 250 255 Phe Ala Thr Pro Phe Tyr Lys Gln Gly Gly Gln Gln Val Lys Ala Ile 260 265 270 Arg Val Glu Gln Val Gln Lys Ser Gly Val Leu Val Arg Glu Asn Asn 275 280 285 Gly Val Ala Asp Asn Ala Ser Ile Val Arg Thr Asp Val Phe Ile Lys 290 295 300 Asn Asn Lys Phe Phe Leu Val Pro Ile Tyr Thr Trp Gln Val Ala Lys 305 310 315 320 Gly Ile Leu Pro Asn Lys Ala Ile Val Ala His Lys Asn Glu Asp Glu 325 330 335 Trp Glu Glu Met Asp Glu Gly Ala Lys Phe Lys Phe Ser Leu Phe Pro 340 345 350 Asn Asp Leu Val Glu Leu Lys Thr Lys Lys Glu Tyr Phe Phe Gly Tyr 355 360 365 Tyr Ile Gly Leu Asp Arg Ala Thr Gly Asn Ile Ser Leu Lys Glu His 370 375 380 Asp Gly Glu Ile Ser Lys Gly Lys Asp Gly Val Tyr Arg Val Gly Val 385 390 395 400 Lys Leu Ala Leu Ser Phe Glu Lys Tyr Gln Val Asp Glu Leu Gly Lys 405 410 415 Asn Arg Gln Ile Cys Arg Pro Gln Gln Arg Gln Pro Val Arg 420 425 430 <210> 172 <211> 448 <212> PRT <213> Neisseria meningitidis <400> 172 Phe Lys Ala Arg Val Glu Thr Ser Arg Phe Pro Arg Ser Lys Lys Gln 1 5 10 15 Arg Ile Leu Leu Gln Lys Phe Asp Glu Asp Gly Phe Lys Glu Arg Asn 20 25 30 Leu Asn Asp Thr Arg Tyr Val Asn Arg Phe Leu Cys Gln Phe Val Ala 35 40 45 Asp Arg Met Arg Leu Thr Gly Lys Gly Lys Lys Arg Val Phe Ala Ser 50 55 60 Asn Gly Gln Ile Thr Asn Leu Leu Arg Gly Phe Trp Gly Leu Arg Lys 65 70 75 80 Val Arg Ala Glu Asn Asp Arg His His Ala Leu Asp Ala Val Val Val 85 90 95 Ala Cys Ser Thr Val Ala Met Gln Gln Lys Ile Thr Arg Phe Val Arg 100 105 110 Tyr Lys Glu Met Asn Ala Phe Asp Gly Lys Thr Ile Asp Lys Glu Thr 115 120 125 Gly Glu Val Leu His Gln Lys Thr His Phe Pro Gln Pro Trp Glu Phe 130 135 140 Phe Ala Gln Glu Val Met Ile Arg Val Phe Gly Lys Pro Asp Gly Lys 145 150 155 160 Pro Glu Phe Glu Glu Ala Asp Thr Pro Glu Lys Leu Arg Thr Leu Leu 165 170 175 Ala Glu Lys Leu Ser Ser Arg Pro Glu Ala Val His Glu Tyr Val Thr 180 185 190 Pro Leu Phe Val Ser Arg Ala Pro Asn Arg Lys Met Ser Gly Gln Gly 195 200 205 His Met Glu Thr Val Lys Ser Ala Lys Arg Leu Asp Glu Gly Val Ser 210 215 220 Val Leu Arg Val Pro Leu Thr Gln Leu Lys Leu Lys Asp Leu Glu Lys 225 230 235 240 Met Val Asn Arg Glu Arg Glu Pro Lys Leu Tyr Glu Ala Leu Lys Ala 245 250 255 Arg Leu Glu Ala His Lys Asp Asp Pro Ala Lys Ala Phe Ala Glu Pro 260 265 270 Phe Tyr Lys Tyr Asp Lys Ala Gly Asn Arg Thr Gln Gln Val Lys Ala 275 280 285 Val Arg Val Glu Gln Val Gln Lys Thr Gly Val Trp Val Arg Asn His 290 295 300 Asn Gly Ile Ala Asp Asn Ala Thr Met Val Arg Val Asp Val Phe Glu 305 310 315 320 Lys Gly Asp Lys Tyr Tyr Leu Val Pro Ile Tyr Ser Trp Gln Val Ala 325 330 335 Lys Gly Ile Leu Pro Asp Arg Ala Val Val Gln Gly Lys Asp Glu Glu 340 345 350 Asp Trp Gln Leu Ile Asp Asp Ser Phe Asn Phe Lys Phe Ser Leu His 355 360 365 Pro Asn Asp Leu Val Glu Val Ile Thr Lys Lys Ala Arg Met Phe Gly 370 375 380 Tyr Phe Ala Ser Cys His Arg Gly Thr Gly Asn Ile Asn Ile Arg Ile 385 390 395 400 His Asp Leu Asp His Lys Ile Gly Lys Asn Gly Ile Leu Glu Gly Ile 405 410 415 Gly Val Lys Thr Ala Leu Ser Phe Gln Lys Tyr Gln Ile Asp Glu Leu 420 425 430 Gly Lys Glu Ile Arg Pro Cys Arg Leu Lys Lys Arg Pro Pro Val Arg 435 440 445 <210> 173 <211> 381 <212> PRT <213> Campylobacter jejuni <400> 173 Ile Glu Val Leu Ala Lys Asn Leu Pro Thr Lys Lys Gln Lys Arg Ile 1 5 10 15 Leu Asp Lys Asn Tyr Lys Asp Lys Glu Gln Lys Asn Phe Lys Asp Arg 20 25 30 Asn Leu Asn Asp Thr Arg Tyr Ile Ala Arg Leu Val Leu Asn Tyr Thr 35 40 45 Lys Asp Tyr Leu Asp Phe Leu Pro Leu Ser Asp Asp Glu Asn Thr Lys 50 55 60 Leu Asn Asp Thr Gln Lys Gly Ser Lys Val His Val Glu Ala Lys Ser 65 70 75 80 Gly Met Leu Thr Ser Ala Leu Arg His Thr Trp Gly Phe Ser Ala Lys 85 90 95 Asp Arg Asn Asn His Leu His His Ala Ile Asp Ala Val Ile Ile Ala 100 105 110 Tyr Ala Asn Asn Ser Ile Val Lys Ala Phe Ser Asp Phe Lys Lys Glu 115 120 125 Gln Glu Ser Asn Ser Ala Glu Leu Tyr Ala Lys Lys Ile Ser Glu Leu 130 135 140 Asp Tyr Lys Asn Lys Arg Lys Phe Phe Glu Pro Phe Ser Gly Phe Arg 145 150 155 160 Gln Lys Val Leu Asp Lys Ile Asp Glu Ile Phe Val Ser Lys Pro Glu 165 170 175 Arg Lys Lys Pro Ser Gly Ala Leu His Glu Glu Thr Phe Arg Lys Glu 180 185 190 Glu Glu Phe Tyr Gln Ser Tyr Gly Gly Lys Glu Gly Val Leu Lys Ala 195 200 205 Leu Glu Leu Gly Lys Ile Arg Lys Val Asn Gly Lys Ile Val Lys Asn 210 215 220 Gly Asp Met Phe Arg Val Asp Ile Phe Lys His Lys Lys Thr Asn Lys 225 230 235 240 Phe Tyr Ala Val Pro Ile Tyr Thr Met Asp Phe Ala Leu Lys Val Leu 245 250 255 Pro Asn Lys Ala Val Ala Arg Ser Lys Lys Gly Glu Ile Lys Asp Trp 260 265 270 Ile Leu Met Asp Glu Asn Tyr Glu Phe Cys Phe Ser Leu Tyr Lys Asp 275 280 285 Ser Leu Ile Leu Ile Gln Thr Lys Asp Met Gln Glu Pro Glu Phe Val 290 295 300 Tyr Tyr Asn Ala Phe Thr Ser Ser Thr Val Ser Leu Ile Val Ser Lys 305 310 315 320 His Asp Asn Lys Phe Glu Thr Leu Ser Lys Asn Gln Lys Ile Leu Phe 325 330 335 Lys Asn Ala Asn Glu Lys Glu Val Ile Ala Lys Ser Ile Gly Ile Gln 340 345 350 Asn Leu Lys Val Phe Glu Lys Tyr Ile Val Ser Ala Leu Gly Glu Val 355 360 365 Thr Lys Ala Glu Phe Arg Gln Arg Glu Asp Phe Lys Lys 370 375 380 <210> 174 <211> 485 <212> PRT <213> Streptococcus gallolyticus <220> <223> Streptococcus gallolyticus pasteurianus <400> 174 Met Lys Asp Tyr Val Leu Lys Gln Lys Gly Leu Gly Lys Lys Lys Arg 1 5 10 15 Asp Tyr Leu Leu Thr Thr Glu Asn Ile Asp Lys Ile Glu Val Lys Lys 20 25 30 Lys Phe Ile Glu Arg Asn Leu Val Asp Thr Arg Tyr Ala Ser Arg Val 35 40 45 Val Leu Asn Ser Leu Gln Ser Ala Leu Arg Glu Leu Gly Lys Asp Thr 50 55 60 Lys Val Ser Val Val Arg Gly Gln Phe Thr Ser Gln Leu Arg Arg Lys 65 70 75 80 Trp Lys Ile Asp Lys Ser Arg Glu Thr Tyr His His His Ala Val Asp 85 90 95 Ala Leu Ile Ile Ala Ala Ser Ser Gln Leu Lys Leu Trp Glu Lys Gln 100 105 110 Asp Asn Pro Met Phe Val Asp Tyr Gly Lys Asn Gln Val Val Asp Lys 115 120 125 Gln Thr Gly Glu Ile Leu Ser Val Ser Asp Asp Glu Tyr Lys Glu Leu 130 135 140 Val Phe Gln Pro Pro Tyr Gln Gly Phe Val Asn Thr Ile Ser Ser Lys 145 150 155 160 Gly Phe Glu Asp Glu Ile Leu Phe Ser Tyr Gln Val Asp Ser Lys Tyr 165 170 175 Asn Arg Lys Val Ser Asp Ala Thr Ile Tyr Ser Thr Arg Lys Ala Lys 180 185 190 Ile Gly Lys Asp Lys Lys Glu Glu Thr Tyr Val Leu Gly Lys Ile Lys 195 200 205 Asp Ile Tyr Ser Gln Asn Gly Phe Asp Thr Phe Ile Lys Lys Tyr Asn 210 215 220 Lys Asp Lys Thr Gln Phe Leu Met Tyr Gln Lys Asp Ser Leu Thr Trp 225 230 235 240 Glu Asn Val Ile Glu Val Ile Leu Arg Asp Tyr Pro Thr Thr Lys Lys 245 250 255 Ser Glu Asp Gly Lys Asn Asp Val Lys Cys Asn Pro Phe Glu Glu Tyr 260 265 270 Arg Arg Glu Asn Gly Leu Ile Cys Lys Tyr Ser Lys Lys Gly Lys Gly 275 280 285 Thr Pro Ile Lys Ser Leu Lys Tyr Tyr Asp Lys Lys Leu Gly Asn Cys 290 295 300 Ile Asp Ile Thr Pro Glu Glu Ser Arg Asn Lys Val Ile Leu Gln Ser 305 310 315 320 Ile Asn Pro Trp Arg Ala Asp Val Tyr Phe Asn Pro Glu Thr Leu Lys 325 330 335 Tyr Glu Leu Met Gly Leu Lys Tyr Ser Asp Leu Ser Phe Glu Lys Gly 340 345 350 Thr Gly Asn Tyr His Ile Ser Gln Glu Lys Tyr Asp Ala Ile Lys Glu 355 360 365 Lys Glu Gly Ile Gly Lys Lys Ser Glu Phe Lys Phe Thr Leu Tyr Arg 370 375 380 Asn Asp Leu Ile Leu Ile Lys Asp Ile Ala Ser Gly Glu Gln Glu Ile 385 390 395 400 Tyr Arg Phe Leu Ser Arg Thr Met Pro Asn Val Asn His Tyr Val Glu 405 410 415 Leu Lys Pro Tyr Asp Lys Glu Lys Phe Asp Asn Val Gln Glu Leu Val 420 425 430 Glu Ala Leu Gly Glu Ala Asp Lys Val Gly Arg Cys Ile Lys Gly Leu 435 440 445 Asn Lys Pro Asn Ile Ser Ile Tyr Lys Val Arg Thr Asp Val Leu Gly 450 455 460 Asn Lys Tyr Phe Val Lys Lys Lys Gly Asp Lys Pro Lys Leu Asp Phe 465 470 475 480 Lys Asn Asn Lys Lys 485 <210> 175 <211> 476 <212> PRT <213> Streptococcus thermophilus <400> 175 Leu Lys Ala Phe Val Arg Glu Ser Lys Thr Leu Ser Asn Lys Lys Lys 1 5 10 15 Glu Tyr Leu Leu Thr Glu Glu Asp Ile Ser Lys Phe Asp Val Arg Lys 20 25 30 Lys Phe Ile Glu Arg Asn Leu Val Asp Thr Arg Tyr Ala Ser Arg Val 35 40 45 Val Leu Asn Ala Leu Gln Glu His Phe Arg Ala His Lys Ile Asp Thr 50 55 60 Lys Val Ser Val Val Arg Gly Gln Phe Thr Ser Gln Leu Arg Arg His 65 70 75 80 Trp Gly Ile Glu Lys Thr Arg Asp Thr Tyr His His His Ala Val Asp 85 90 95 Ala Leu Ile Ile Ala Ala Ser Ser Gln Leu Asn Leu Trp Lys Lys Gln 100 105 110 Lys Asn Thr Leu Val Ser Tyr Ser Glu Asp Gln Leu Leu Asp Ile Glu 115 120 125 Thr Gly Glu Leu Ile Ser Asp Asp Glu Tyr Lys Glu Ser Val Phe Lys 130 135 140 Ala Pro Tyr Gln His Phe Val Asp Thr Leu Lys Ser Lys Glu Phe Glu 145 150 155 160 Asp Ser Ile Leu Phe Ser Tyr Gln Val Asp Ser Lys Phe Asn Arg Lys 165 170 175 Ile Ser Asp Ala Thr Ile Tyr Ala Thr Arg Gln Ala Lys Val Gly Lys 180 185 190 Asp Lys Ala Asp Glu Thr Tyr Val Leu Gly Lys Ile Lys Asp Ile Tyr 195 200 205 Thr Gln Asp Gly Tyr Asp Ala Phe Met Lys Ile Tyr Lys Lys Asp Lys 210 215 220 Ser Lys Phe Leu Met Tyr Arg His Asp Pro Gln Thr Phe Glu Lys Val 225 230 235 240 Ile Glu Pro Ile Leu Glu Asn Tyr Pro Asn Lys Gln Ile Asn Glu Lys 245 250 255 Gly Lys Glu Val Pro Cys Asn Pro Phe Leu Lys Tyr Lys Glu Glu His 260 265 270 Gly Tyr Ile Arg Lys Tyr Ser Lys Lys Gly Asn Gly Pro Glu Ile Lys 275 280 285 Ser Leu Lys Tyr Tyr Asp Ser Lys Leu Gly Asn His Ile Asp Ile Thr 290 295 300 Pro Lys Asp Ser Asn Asn Lys Val Val Leu Gln Ser Val Ser Pro Trp 305 310 315 320 Arg Ala Asp Val Tyr Phe Asn Lys Thr Thr Gly Lys Tyr Glu Ile Leu 325 330 335 Gly Leu Lys Tyr Ala Asp Leu Gln Phe Glu Lys Gly Thr Gly Thr Tyr 340 345 350 Lys Ile Ser Gln Glu Lys Tyr Asn Asp Ile Lys Lys Lys Glu Gly Val 355 360 365 Asp Ser Asp Ser Glu Phe Lys Phe Thr Leu Tyr Lys Asn Asp Leu Leu 370 375 380 Leu Val Lys Asp Thr Glu Thr Lys Glu Gln Gln Leu Phe Arg Phe Leu 385 390 395 400 Ser Arg Thr Met Pro Lys Gln Lys His Tyr Val Glu Leu Lys Pro Tyr 405 410 415 Asp Lys Gln Lys Phe Glu Gly Gly Glu Ala Leu Ile Lys Val Leu Gly 420 425 430 Asn Val Ala Asn Ser Gly Gln Cys Lys Lys Gly Leu Gly Lys Ser Asn 435 440 445 Ile Ser Ile Tyr Lys Val Arg Thr Asp Val Leu Gly Asn Gln His Ile 450 455 460 Ile Lys Asn Glu Gly Asp Lys Pro Lys Leu Asp Phe 465 470 475 <210> 176 <211> 450 <212> PRT <213> Staphylococcus aureus <400> 176 Phe Lys Lys His Ile Leu Asn Leu Ala Lys Gly Lys Gly Arg Ile Ser 1 5 10 15 Lys Thr Lys Lys Glu Tyr Leu Leu Glu Glu Arg Asp Ile Asn Arg Phe 20 25 30 Ser Val Gln Lys Asp Phe Ile Asn Arg Asn Leu Val Asp Thr Arg Tyr 35 40 45 Ala Thr Arg Gly Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn 50 55 60 Asn Leu Asp Val Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe 65 70 75 80 Leu Arg Arg Lys Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys 85 90 95 His His Ala Glu Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe 100 105 110 Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln 115 120 125 Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu 130 135 140 Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile 145 150 155 160 Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro 165 170 175 Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp 180 185 190 Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys 195 200 205 Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu 210 215 220 Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile 225 230 235 240 Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu 245 250 255 Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro 260 265 270 Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu 275 280 285 Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu 290 295 300 Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr 305 310 315 320 Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr 325 330 335 Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys 340 345 350 Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe Tyr Asn Asn Asp Leu 355 360 365 Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile Gly Val Asn Asn Asp 370 375 380 Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp Ile Thr Tyr Arg Glu 385 390 395 400 Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro Arg Ile Ile Lys Thr 405 410 415 Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr Ser Thr Asp Ile Leu 420 425 430 Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His Pro Gln Ile Ile Lys 435 440 445 Lys Gly 450 <210> 177 <400> 177 000 <210> 178 <400> 178 000 <210> 179 <400> 179 000 <210> 180 <400> 180 000 <210> 181 <400> 181 000 <210> 182 <400> 182 000 <210> 183 <400> 183 000 <210> 184 <400> 184 000 <210> 185 <400> 185 000 <210> 186 <400> 186 000 <210> 187 <400> 187 000 <210> 188 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic peptide <400> 188 Gly Gly Gly Ser 1 <210> 189 <211> 5 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic peptide <400> 189 Gly Gly Gly Gly Ser 1 5 <210> 190 <211> 33 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 190 ctagagggca cgggcagctt gccggtgggc atg 33 <210> 191 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 191 cccaccggca agctgcccgt gccct 25 <210> 192 <211> 34 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 192 ctagaggtcg ccctcgaact tcacctcggg catg 34 <210> 193 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 193 cccgaggtga agttcgaggg cgacct 26 <210> 194 <211> 33 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 194 aattcgggca cgggcagctt gccggtgggc atg 33 <210> 195 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 195 cccaccggca agctgcccgt gcccg 25 <210> 196 <211> 34 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 196 aattcggtcg ccctcgaact tcacctcggg catg 34 <210> 197 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 197 cccgaggtga agttcgaggg cgaccg 26 <210> 198 <211> 60 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (31)..(36) <223> a, c, t, g, unknown or other <220> <221> modified_base <222> (39)..(41) <223> a, c, t, g, unknown or other <400> 198 gcaggaattc gggcacgggc agcttgccgg nnnnnnctnn ngcgcaggtc acgaggcatg 60 <210> 199 <211> 60 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (31)..(36) <223> a, c, t, g, unknown or other <220> <221> modified_base <222> (39)..(41) <223> a, c, t, g, unknown or other <400> 199 gcaggaattc gtcgccctcg aacttcacct nnnnnnctnn ngcgcaggtc acgaggcatg 60 <210> 200 <211> 15 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic primer <400> 200 cctcgtgacc tgcgc 15 <210> 201 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic primer <400> 201 gataccgctc gccgcagc 18 <210> 202 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic primer <400> 202 ctgcgttctg atttaatctg tatcaggc 28 <210> 203 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic primer <400> 203 ggagatgtaa atcacctcca tctga 25 <210> 204 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic primer <400> 204 atgttagcct acctcgaaaa ccttc 25 <210> 205 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic primer <400> 205 cctgtgctct cctgttttta ggtat 25 <210> 206 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic primer <400> 206 aacatggtaa gaagcgtgag tgttt 25 <210> 207 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic primer <400> 207 caggctgttg aaccgtagat ttagt 25 <210> 208 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic primer <400> 208 tccacatgtt ttgagtttga gagtc 25 <210> 209 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic primer <400> 209 ggagcagctg gtcagagggg 20 <210> 210 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic primer <400> 210 ccatagggaa gggggacact gg 22 <210> 211 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic primer <400> 211 gggccgggaa agagttgctg 20 <210> 212 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic primer <400> 212 gccctacatc tgctctccct cc 22 <210> 213 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic primer <400> 213 ccagcacaac ttactcgcac ttgac 25 <210> 214 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic primer <400> 214 catcaccaac ccacagccaa gg 22 <210> 215 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic primer <400> 215 gatgagggct ccagatggca c 21 <210> 216 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic primer <400> 216 gaggagggag caggaaagtg agg 23 <210> 217 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 217 gggcacgggc agcttgccgg 20 <210> 218 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 218 gggcacgggc agcttgccgg tggt 24 <210> 219 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 219 gtcgccctcg aacttcacct 20 <210> 220 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 220 gtcgccctcg aacttcacct cggc 24 <210> 221 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 221 ggtcgccacc atggtgagca 20 <210> 222 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 222 ggtcgccacc atggtgagca aggg 24 <210> 223 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 223 ggtcagggtg gtcacgaggg 20 <210> 224 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 224 ggtcagggtg gtcacgaggg tggg 24 <210> 225 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 225 ggtggtgcag atgaacttca 20 <210> 226 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 226 ggtggtgcag atgaacttca gggt 24 <210> 227 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 227 gggtggtgcc catcctggtc 20 <210> 228 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 228 gggtggtgcc catcctggtc gagc 24 <210> 229 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 229 gacgtaaacg gccacaagtt 20 <210> 230 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 230 gacgtaaacg gccacaagtt cagc 24 <210> 231 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 231 gtgcagatga acttcagggt 20 <210> 232 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 232 gtgcagatga acttcagggt cagc 24 <210> 233 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 233 gggtggtcac gagggtgggc 20 <210> 234 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 234 gggtggtcac gagggtgggc cagg 24 <210> 235 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 235 ggtcgagctg gacggcgacg 20 <210> 236 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 236 ggtcgagctg gacggcgacg taaa 24 <210> 237 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 237 gtcgagctgg acggcgacgt 20 <210> 238 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 238 gtcgagctgg acggcgacgt aaac 24 <210> 239 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 239 ggggtggtgc ccatcctggt 20 <210> 240 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 240 ggggtggtgc ccatcctggt cgag 24 <210> 241 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 241 gccaccatgg tgagcaaggg 20 <210> 242 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 242 gccaccatgg tgagcaaggg cgag 24 <210> 243 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 243 gtcgccgtcc agctcgacca 20 <210> 244 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 244 gtcgccgtcc agctcgacca ggat 24 <210> 245 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 245 gcatcgccct cgccctcgcc 20 <210> 246 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 246 gcatcgccct cgccctcgcc ggac 24 <210> 247 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 247 gttcgagggc gacaccctgg 20 <210> 248 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 248 gttcgagggc gacaccctgg tgaa 24 <210> 249 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 249 gttcgagggc gacaccctgg 20 <210> 250 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 250 gttcgagggc gacaccctgg tgaa 24 <210> 251 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 251 gttcaccagg gtgtcgccct 20 <210> 252 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 252 gttcaccagg gtgtcgccct cgaa 24 <210> 253 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 253 gcagaagaac ggcatcaagg 20 <210> 254 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 254 gcagaagaac ggcatcaagg tgaa 24 <210> 255 <211> 17 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 255 gaagaacggc atcaagg 17 <210> 256 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 256 gaagaacggc atcaaggtga a 21 <210> 257 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 257 gcccaccctc gtgaccaccc 20 <210> 258 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 258 gcccaccctc gtgaccaccc tgac 24 <210> 259 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 259 gcccttgctc accatggtgg 20 <210> 260 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 260 gcccttgctc accatggtgg cgac 24 <210> 261 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 261 gtcgccgtcc agctcgacca 20 <210> 262 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 262 gtcgccgtcc agctcgacca ggat 24 <210> 263 <211> 17 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 263 gccgtccagc tcgacca 17 <210> 264 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 264 gccgtccagc tcgaccagga t 21 <210> 265 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 265 gtgtccggcg agggcgaggg 20 <210> 266 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 266 gtgtccggcg agggcgaggg cgat 24 <210> 267 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 267 gggcagcttg ccggtggtgc 20 <210> 268 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 268 gggcagcttg ccggtggtgc agat 24 <210> 269 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 269 ggcagcttgc cggtggtgc 19 <210> 270 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 270 ggcagcttgc cggtggtgca gat 23 <210> 271 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 271 gcagcttgcc ggtggtgc 18 <210> 272 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 272 gcagcttgcc ggtggtgcag at 22 <210> 273 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 273 ggggtggtgc ccatcctggt 20 <210> 274 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 274 ggggtggtgc ccatcctggt cgag 24 <210> 275 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 275 gggtggtgcc catcctggt 19 <210> 276 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 276 gggtggtgcc catcctggtc gag 23 <210> 277 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 277 ggtggtgccc atcctggt 18 <210> 278 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 278 ggtggtgccc atcctggtcg ag 22 <210> 279 <211> 17 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 279 gtggtgccca tcctggt 17 <210> 280 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 280 gtggtgccca tcctggtcga g 21 <210> 281 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 281 gccaccatgg tgagcaaggg 20 <210> 282 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 282 gccaccatgg tgagcaaggg cgag 24 <210> 283 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 283 gccgtaggtc agggtggtca 20 <210> 284 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 284 gccgtaggtc agggtggtca cgag 24 <210> 285 <211> 17 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 285 gtaggtcagg gtggtca 17 <210> 286 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 286 gtaggtcagg gtggtcacga g 21 <210> 287 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 287 gctgcccgac aaccactacc 20 <210> 288 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 288 gctgcccgac aaccactacc tgag 24 <210> 289 <211> 17 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 289 gcccgacaac cactacc 17 <210> 290 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 290 gcccgacaac cactacctga g 21 <210> 291 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 291 gcgagggcga tgccacctac 20 <210> 292 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 292 gcgagggcga tgccacctac ggca 24 <210> 293 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 293 gtggtcgggg tagcggctga 20 <210> 294 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 294 gtggtcgggg tagcggctga agca 24 <210> 295 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 295 ggagctgttc accggggtgg 20 <210> 296 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 296 ggagctgttc accggggtgg tgcc 24 <210> 297 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 297 gaacttgtgg ccgtttacgt 20 <210> 298 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 298 gaacttgtgg ccgtttacgt cgcc 24 <210> 299 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 299 ggtgaacagc tcctcgccct 20 <210> 300 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 300 ggtgaacagc tcctcgccct tgct 24 <210> 301 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 301 ggtggtgccc atcctggtcg 20 <210> 302 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 302 ggtggtgccc atcctggtcg agct 24 <210> 303 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 303 gccacaagtt cagcgtgtcc 20 <210> 304 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 304 gccacaagtt cagcgtgtcc ggcg 24 <210> 305 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 305 gcgtgtccgg cgagggcgag 20 <210> 306 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 306 gcgtgtccgg cgagggcgag ggcg 24 <210> 307 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 307 gtgtccggcg agggcgag 18 <210> 308 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 308 gtgtccggcg agggcgaggg cg 22 <210> 309 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 309 gcccgaaggc tacgtccagg 20 <210> 310 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 310 gcccgaaggc tacgtccagg agcg 24 <210> 311 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 311 gtcgtccttg aagaagatgg 20 <210> 312 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 312 gtcgtccttg aagaagatgg tgcg 24 <210> 313 <211> 17 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 313 gtccttgaag aagatgg 17 <210> 314 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 314 gtccttgaag aagatggtgc g 21 <210> 315 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 315 ggtcgccacc atggtgagca 20 <210> 316 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 316 ggtcgccacc atggtgagca aggg 24 <210> 317 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 317 ggtggtcacg agggtgggcc 20 <210> 318 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 318 ggtggtcacg agggtgggcc aggg 24 <210> 319 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 319 gatccaccgg tcgccaccat 20 <210> 320 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 320 gatccaccgg tcgccaccat ggtg 24 <210> 321 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 321 gtaaacggcc acaagttcag 20 <210> 322 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 322 gtaaacggcc acaagttcag cgtg 24 <210> 323 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 323 gagtccgagc agaagaagaa 20 <210> 324 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 324 gagtccgagc agaagaagaa gggc 24 <210> 325 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 325 gtcacctcca atgactaggg 20 <210> 326 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 326 gtcacctcca atgactaggg tggg 24 <210> 327 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 327 gaggaggaag ggcctgagtc 20 <210> 328 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 328 gaggaggaag ggcctgagtc cgag 24 <210> 329 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 329 ggttgcccac cctagtcatt 20 <210> 330 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 330 ggttgcccac cctagtcatt ggag 24 <210> 331 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 331 gctgagctga gagcctgatg 20 <210> 332 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 332 gctgagctga gagcctgatg ggaa 24 <210> 333 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 333 gccacgaagc aggccaatgg 20 <210> 334 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 334 gccacgaagc aggccaatgg ggag 24 <210> 335 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 335 ggaatccctt ctgcagcacc 20 <210> 336 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 336 ggaatccctt ctgcagcacc tgga 24 <210> 337 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 337 gctgcagaag ggattccatg 20 <210> 338 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 338 gctgcagaag ggattccatg aggt 24 <210> 339 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 339 gaatcccttc tgcagcacct 20 <210> 340 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 340 gaatcccttc tgcagcacct ggat 24 <210> 341 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 341 gtgctgcaga agggattcca 20 <210> 342 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 342 gtgctgcaga agggattcca tgag 24 <210> 343 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 343 gcggcggctg cacaaccagt 20 <210> 344 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 344 gcggcggctg cacaaccagt ggag 24 <210> 345 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 345 ggttgtgcag ccgccgctcc 20 <210> 346 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 346 ggttgtgcag ccgccgctcc agag 24 <210> 347 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 347 gaggcaagag ggcggctttg 20 <210> 348 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 348 gaggcaagag ggcggctttg ggcg 24 <210> 349 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 349 ggggtccagt tccgggatt 19 <210> 350 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 350 ggggtccagt tccgggatta gcg 23 <210> 351 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 351 gcagaaggga ttccatgagg 20 <210> 352 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 352 gcagaaggga ttccatgagg tgcg 24 <210> 353 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 353 gaagggattc catgaggtg 19 <210> 354 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 354 gaagggattc catgaggtgc gcg 23 <210> 355 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 355 gctgaaacag tgacctgtct 20 <210> 356 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 356 gctgaaacag tgacctgtct tggt 24 <210> 357 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 357 gatgtagggc tagaggggtg 20 <210> 358 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 358 gatgtagggc tagaggggtg aggc 24 <210> 359 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 359 ggtgcatttt caggaggaag 20 <210> 360 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 360 ggtgcatttt caggaggaag cgat 24 <210> 361 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 361 gttttcgctc cgaaggtaaa 20 <210> 362 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 362 gttttcgctc cgaaggtaaa agaa 24 <210> 363 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 363 gagatgtagg gctagagggg 20 <210> 364 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 364 gagatgtagg gctagagggg tgag 24 <210> 365 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 365 gcagagggga gaagaaagag 20 <210> 366 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 366 gcagagggga gaagaaagag agat 24 <210> 367 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 367 gggtgcattt tcaggagga 19 <210> 368 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 368 gggtgcattt tcaggaggaa gcg 23 <210> 369 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 369 ggtgagtgag tgtgtgcgtg 20 <210> 370 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 370 ggtgagtgag tgtgtgcgtg tggg 24 <210> 371 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 371 gttggagcgg ggagaaggcc 20 <210> 372 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 372 gttggagcgg ggagaaggcc aggg 24 <210> 373 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 373 gcgagcagcg tcttcgagag 20 <210> 374 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 374 gcgagcagcg tcttcgagag tgag 24 <210> 375 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 375 gacgtgtgtg tctgtgtggg 20 <210> 376 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 376 gacgtgtgtg tctgtgtggg tgag 24 <210> 377 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 377 ggttgagggc gttggagcgg 20 <210> 378 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 378 ggttgagggc gttggagcgg ggag 24 <210> 379 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 379 gctttggaaa gggggtgggg 20 <210> 380 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 380 gctttggaaa gggggtgggg ggag 24 <210> 381 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 381 gcagacggca gtcactaggg 20 <210> 382 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 382 gcagacggca gtcactaggg ggcg 24 <210> 383 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 383 gctgggtgaa tggagcgagc 20 <210> 384 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 384 gctgggtgaa tggagcgagc agcg 24 <210> 385 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 385 gtgtgggtga gtgagtgtg 19 <210> 386 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 386 gtgtgggtga gtgagtgtgt gcg 23 <210> 387 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 387 gtgtgcgtgt ggggttgag 19 <210> 388 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 388 gtgtgcgtgt ggggttgagg gcg 23 <210> 389 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 389 gtcgtgctgc ttcatgtggt 20 <210> 390 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 390 gtcgtgctgc ttcatgtggt cggggt 26 <210> 391 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 391 gaagtcgtgc tgcttcatgt ggt 23 <210> 392 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 392 gaagtcgtgc tgcttcatgt ggtcggggt 29 <210> 393 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 393 gccggtggtg cagatgaact t 21 <210> 394 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 394 gccggtggtg cagatgaact tcagggt 27 <210> 395 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 395 gccgtaggtc agggtggtca c 21 <210> 396 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 396 gccgtaggtc agggtggtca cgagggt 27 <210> 397 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 397 gcaacatcct ggggcacaag c 21 <210> 398 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 398 gcaacatcct ggggcacaag ctggagt 27 <210> 399 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 399 ggcaacatcc tggggcacaa gc 22 <210> 400 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 400 ggcaacatcc tggggcacaa gctggagt 28 <210> 401 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 401 gaagcactgc acgccgtagg t 21 <210> 402 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 402 gaagcactgc acgccgtagg tcagggt 27 <210> 403 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 403 gctgaagcac tgcacgccgt aggt 24 <210> 404 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 404 gctgaagcac tgcacgccgt aggtcagggt 30 <210> 405 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 405 gccctcgaac ttcacctcgg c 21 <210> 406 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 406 gccctcgaac ttcacctcgg cgcgggt 27 <210> 407 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 407 gtcgccctcg aacttcacct cggc 24 <210> 408 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 408 gtcgccctcg aacttcacct cggcgcgggt 30 <210> 409 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 409 gcaagggcga ggagctgttc ac 22 <210> 410 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 410 gcaagggcga ggagctgttc accggggt 28 <210> 411 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 411 gagcaagggc gaggagctgt tcac 24 <210> 412 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 412 gagcaagggc gaggagctgt tcaccggggt 30 <210> 413 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 413 gcccttcagc tcgatgcggt tcac 24 <210> 414 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 414 gcccttcagc tcgatgcggt tcaccagggt 30 <210> 415 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 415 gtctatatca tggccgacaa 20 <210> 416 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 416 gtctatatca tggccgacaa gcagaa 26 <210> 417 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 417 gcagctcgcc gaccactacc a 21 <210> 418 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 418 gcagctcgcc gaccactacc agcagaa 27 <210> 419 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 419 gtgcagctcg ccgaccacta cca 23 <210> 420 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 420 gtgcagctcg ccgaccacta ccagcagaa 29 <210> 421 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 421 gccttcgggc atggcggact t 21 <210> 422 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 422 gccttcgggc atggcggact tgaagaa 27 <210> 423 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 423 gtagccttcg ggcatggcgg actt 24 <210> 424 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 424 gtagccttcg ggcatggcgg acttgaagaa 30 <210> 425 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 425 gtctatatca tggccgacaa gca 23 <210> 426 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 426 gtctatatca tggccgacaa gcagaagaa 29 <210> 427 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 427 gtcttgtagt tgccgtcgtc ctt 23 <210> 428 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 428 gtcttgtagt tgccgtcgtc cttgaagaa 29 <210> 429 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 429 ggtcttgtag ttgccgtcgt cctt 24 <210> 430 <211> 30 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 430 ggtcttgtag ttgccgtcgt ccttgaagaa 30 <210> 431 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 431 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Arg Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 432 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 432 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Arg Tyr 225 230 235 240 Ile Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 433 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 433 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asn Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Phe Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 434 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 434 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Arg Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 435 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 435 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asn Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Arg Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Arg Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 436 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 436 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Val Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Asn Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Arg Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 437 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 437 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Pro Ile Asp Arg Lys Arg Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 438 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 438 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 439 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 439 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Val Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Lys Leu Gly Ala 210 215 220 Pro Ala Ala Ile Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 440 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 440 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Glu Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 441 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 441 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Met Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 442 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 442 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Val Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Glu Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 443 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 443 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Glu Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Phe Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ser Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 444 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 444 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Phe Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Leu Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Ile Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 445 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 445 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Lys Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 446 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 446 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Glu 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Cys Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 447 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 447 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Asn Arg Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Arg Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Ala Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 448 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 448 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Val Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Asn Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Thr Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 449 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 449 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Leu Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Arg His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys Tyr Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 450 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 450 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Val Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 451 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 451 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Ile Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 452 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 452 Lys Thr Glu Val Gln Thr Gly Arg Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asn Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 453 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 453 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile His Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 454 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 454 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 455 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 455 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asn Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Met Ile Asp Arg Lys Gln Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Val Gly Asp 260 265 270 <210> 456 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 456 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Arg Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 457 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 457 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Leu Leu Gly Gly Asp 260 265 270 <210> 458 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 458 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Asn Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Lys Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 459 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 459 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Lys Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 460 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 460 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asn Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 461 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 461 Glu Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val Ala Phe Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Phe Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 462 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 462 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Asp Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Val Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 463 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 463 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Asn Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Glu Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Ala Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 464 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 464 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Tyr Arg Lys Gln Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 465 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 465 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Asn Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asp Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 466 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 466 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asn Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Arg Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Phe Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 467 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 467 Lys Thr Glu Met Gln Thr Gly Gly Phe Ser Lys Glu Ser Val Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asn Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Arg Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Val Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Asp Asp Asn Glu Gln Lys Arg 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Arg Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 468 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 468 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Glu 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Lys Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Lys His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 469 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 469 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asn Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Asn Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Tyr Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Val Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 470 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 470 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Val Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Phe 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 471 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 471 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Leu Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Arg Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 472 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 472 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asn Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Asp Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Cys Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Lys Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 473 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 473 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Val Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 474 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 474 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Ile Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Val Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 475 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 475 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Ile Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Thr Ile Arg Glu 195 200 205 Gln Ala Glu Asn Thr Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 476 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 476 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His His Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 477 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 477 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Gly Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 478 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 478 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Leu Ile Lys Leu Pro Lys Tyr Asn Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 479 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 479 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asn Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Asp Tyr Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 480 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 480 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asp Ser Pro Lys Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Met Ser Gln Leu Gly Gly Asp 260 265 270 <210> 481 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 481 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ile Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 482 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 482 Lys Thr Glu Glu Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile His Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe His Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Met His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Glu Gly Asp 260 265 270 <210> 483 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 483 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Met Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 484 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 484 Lys Thr Glu Val Gln Thr Gly Arg Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Val Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 485 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 485 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Val Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Val Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 486 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 486 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Phe Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Met Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 487 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 487 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Val Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln Pro Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 488 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 488 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Val Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Ile Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Lys Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 489 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 489 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 490 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 490 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Val Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 491 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 491 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 492 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 492 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 493 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 493 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Phe Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Pro Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 494 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 494 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Leu Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 495 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 495 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 496 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 496 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Ile Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 497 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 497 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 498 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 498 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Thr Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Ile Lys 85 90 95 Asp Phe Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Gln Tyr 225 230 235 240 Arg Ser Pro Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 499 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 499 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 500 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 500 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Pro 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Ser 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Glu Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 501 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 501 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Asn Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Thr Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 502 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 502 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile His Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Thr Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 503 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 503 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Met Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Lys Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Lys Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Thr Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His His Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 504 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 504 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Arg Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Thr Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 505 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 505 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Leu Tyr Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Arg 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Lys Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Thr Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Val Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 506 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 506 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile His Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asn Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Thr Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ser Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Thr Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 507 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 507 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Gly Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asn Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Thr Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 508 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 508 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Asp Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Met Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Arg Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Val His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Thr Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 509 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 509 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asn Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Ile Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Val Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Thr Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 510 <211> 272 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 510 Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile His Pro 1 5 10 15 Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro 20 25 30 Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val Ala Tyr Ser Val Leu 35 40 45 Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val 50 55 60 Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys 65 70 75 80 Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys 85 90 95 Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn 100 105 110 Gly Arg Lys Arg Met Leu Ala Ser Ala Arg Glu Leu Gln Lys Gly Asn 115 120 125 Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser 130 135 140 His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln 145 150 155 160 Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln 165 170 175 Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp 180 185 190 Lys Val Leu Ser Ala Tyr Asn Lys Asp Arg Asp Lys Pro Ile Arg Glu 195 200 205 Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala 210 215 220 Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Thr Tyr 225 230 235 240 Arg Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile 245 250 255 Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 260 265 270 <210> 511 <211> 6 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (1)..(2) <223> a, c, t, g, unknown or other <400> 511 nncagt 6 <210> 512 <211> 6 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (1)..(2) <223> a, c, t, g, unknown or other <400> 512 nncggt 6 <210> 513 <211> 6 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (1)..(2) <223> a, c, t, g, unknown or other <400> 513 nntagt 6 <210> 514 <211> 6 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (1)..(2) <223> a, c, t, g, unknown or other <400> 514 nntggt 6 <210> 515 <211> 50 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 515 ctagagggtg ggcgggaggg tcgccctcga acttcacctt ggagtgcatg 50 <210> 516 <211> 42 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 516 cactccaagg tgaagttcga gggcgaccct cccgcccacc ct 42 <210> 517 <211> 67 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (36)..(43) <223> a, c, t, g, unknown or other <220> <221> modified_base <222> (46)..(48) <223> a, c, t, g, unknown or other <400> 517 gcaggaattc gggaggggca cgggcagctt gccggnnnnn nnnctnnngc gcaggtcacg 60 aggcatg 67 <210> 518 <211> 67 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (36)..(43) <223> a, c, t, g, unknown or other <220> <221> modified_base <222> (46)..(48) <223> a, c, t, g, unknown or other <400> 518 gcaggaattc ggagggtcgc cctcgaactt cacctnnnnn nnnctnnngc gcaggtcacg 60 aggcatg 67 <210> 519 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 519 gttgtactcc agcttgtgcc c 21 <210> 520 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 520 gttgtactcc agcttgtgcc ccaggat 27 <210> 521 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 521 ggacggcgac gtaaacggcc 20 <210> 522 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 522 ggacggcgac gtaaacggcc acaagt 26 <210> 523 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 523 gaacttcagg gtcagcttgc c 21 <210> 524 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 524 gaacttcagg gtcagcttgc cgtaggt 27 <210> 525 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 525 gtcgatgccc ttcagctcga 20 <210> 526 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 526 gtcgatgccc ttcagctcga tgcggt 26 <210> 527 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 527 gtgaccaccc tgacctacgg cg 22 <210> 528 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 528 gtgaccaccc tgacctacgg cgtgcagt 28 <210> 529 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 529 gatatagacg ttgtggctgt 20 <210> 530 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 530 gatatagacg ttgtggctgt tgtagt 26 <210> 531 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 531 ggtgaagttc gagggcgaca c 21 <210> 532 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 532 ggtgaagttc gagggcgaca ccctggt 27 <210> 533 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 533 gcgtgtccgg cgagggcgag ggcgat 26 <210> 534 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 534 gctcgaccag gatgggcacc ac 22 <210> 535 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 535 gctcgaccag gatgggcacc accccggt 28 <210> 536 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 536 gggcgaggag ctgttcaccg g 21 <210> 537 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 537 gggcgaggag ctgttcaccg gggtggt 27 <210> 538 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 538 gcactgcacg ccgtaggtca g 21 <210> 539 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 539 gcactgcacg ccgtaggtca gggtggt 27 <210> 540 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 540 gtgtggttcc agaaccggag ga 22 <210> 541 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 541 gtgtggttcc agaaccggag gacaaagt 28 <210> 542 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 542 gcaggctctc cgaggagaag g 21 <210> 543 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 543 gcaggctctc cgaggagaag gccaagt 27 <210> 544 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 544 gcccctccct ccctggccca ggt 23 <210> 545 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 545 gcccctccct ccctggccca ggtgaaggt 29 <210> 546 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 546 gctcagcctg agtgttgagg c 21 <210> 547 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 547 gctcagcctg agtgttgagg ccccagt 27 <210> 548 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 548 gcctgcttcg tggcaatgcg cc 22 <210> 549 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 549 gcctgcttcg tggcaatgcg ccaccggt 28 <210> 550 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 550 gcaaccacaa acccacgagg g 21 <210> 551 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 551 gcaaccacaa acccacgagg gcagagt 27 <210> 552 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 552 ggcctcccca aagcctggcc a 21 <210> 553 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 553 ggcctcccca aagcctggcc agggagt 27 <210> 554 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 554 gcagaagctg gaggaggaag ggc 23 <210> 555 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 555 gcagaagctg gaggaggaag ggcctgagt 29 <210> 556 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 556 gcttcgtggc aatgcgccac cg 22 <210> 557 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 557 gcttcgtggc aatgcgccac cggttgat 28 <210> 558 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 558 ggctctccga ggagaaggcc a 21 <210> 559 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 559 ggctctccga ggagaaggcc aagtggt 27 <210> 560 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 560 gcctctctgc aatgctattg gt 22 <210> 561 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 561 gcctctctgc aatgctattg gtcgaaat 28 <210> 562 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 562 gcgtactgat tggaacatcc g 21 <210> 563 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 563 gcgtactgat tggaacatcc gcgaaat 27 <210> 564 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 564 gacgtcacag tgaccgaggg cct 23 <210> 565 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 565 gacgtcacag tgaccgaggg cctggaagt 29 <210> 566 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 566 gcccggcgca cggtggcggg gtc 23 <210> 567 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 567 gcccggcgca cggtggcggg gtcccaggt 29 <210> 568 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 568 ggcggggtcc caggtgctga c 21 <210> 569 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 569 ggcggggtcc caggtgctga cgtaggt 27 <210> 570 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 570 ggcgtatcat ttcgcggatg t 21 <210> 571 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 571 ggcgtatcat ttcgcggatg ttccaat 27 <210> 572 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 572 gagaccgcca gaagctcgga aa 22 <210> 573 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 573 gagaccgcca gaagctcgga aaagcgat 28 <210> 574 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 574 ggatcgcttt tccgagcttc t 21 <210> 575 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 575 ggatcgcttt tccgagcttc tggcggt 27 <210> 576 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 576 gcgcccactg caaggcccgg cg 22 <210> 577 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 577 gcgcccactg caaggcccgg cgcacggt 28 <210> 578 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 578 gtagggcctt cgcgcacctc a 21 <210> 579 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 579 gtagggcctt cgcgcacctc atggaat 27 <210> 580 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 580 gcagccgccg ctccagagcc gt 22 <210> 581 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 581 gcagccgccg ctccagagcc gtgcgaat 28 <210> 582 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 582 ggccatgccg accaaagcgc cg 22 <210> 583 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 583 ggccatgccg accaaagcgc cgatggat 28 <210> 584 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 584 gcaaggcccg gcgcacggtg g 21 <210> 585 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 585 gcaaggcccg gcgcacggtg gcggggt 27 <210> 586 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 586 gaggcaagag ggcggctttg gg 22 <210> 587 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 587 gaggcaagag ggcggctttg ggcggggt 28 <210> 588 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 588 gtgaccgagg gcctggaagt tc 22 <210> 589 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 589 gtgaccgagg gcctggaagt tcgctaat 28 <210> 590 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 590 ggggtcccag gtgctgacgt a 21 <210> 591 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 591 ggggtcccag gtgctgacgt aggtagt 27 <210> 592 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 592 gtactgattg gaacatccgc ga 22 <210> 593 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 593 gtactgattg gaacatccgc gaaatgat 28 <210> 594 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 594 gtctgaagcc atcgcttcct cct 23 <210> 595 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 595 gtctgaagcc atcgcttcct cctgaaaat 29 <210> 596 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 596 ggttttcgct ccgaaggtaa a 21 <210> 597 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 597 ggttttcgct ccgaaggtaa aagaaat 27 <210> 598 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 598 gggactcccc aagccctatt a 21 <210> 599 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 599 gggactcccc aagccctatt aaaaaat 27 <210> 600 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 600 gcagcttgtt tcacctcggt gc 22 <210> 601 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 601 gcagcttgtt tcacctcggt gcagagat 28 <210> 602 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 602 gacctgtctt ggttttcgct cc 22 <210> 603 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 603 gacctgtctt ggttttcgct ccgaaggt 28 <210> 604 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 604 gcttccatct gattagtaag taa 23 <210> 605 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 605 gcttccatct gattagtaag taatccaat 29 <210> 606 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 606 gtgcagagat gcctcggtgc ct 22 <210> 607 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 607 gtgcagagat gcctcggtgc ctgccagt 28 <210> 608 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 608 gagggtgcat tttcaggagg a 21 <210> 609 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 609 gagggtgcat tttcaggagg aagcgat 27 <210> 610 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 610 gtttcacctc ggtgcagaga tgc 23 <210> 611 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 611 gtttcacctc ggtgcagaga tgcctcggt 29 <210> 612 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 612 gcgatggctt cagacagcat at 22 <210> 613 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 613 gcgatggctt cagacagcat atttgagt 28 <210> 614 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 614 gctccgaagg taaaagaaat ca 22 <210> 615 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 615 gctccgaagg taaaagaaat cattgagt 28 <210> 616 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 616 gaggcatatg attacaagtc ta 22 <210> 617 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 617 gaggcatatg attacaagtc tattggat 28 <210> 618 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 618 gaaagagaga tgtagggcta g 21 <210> 619 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 619 gaaagagaga tgtagggcta gaggggt 27 <210> 620 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 620 gtactcacct ctcatgaagc act 23 <210> 621 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 621 gtactcacct ctcatgaagc actgtgggt 29 <210> 622 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 622 gaggtgagta catgctggtc t 21 <210> 623 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 623 gaggtgagta catgctggtc ttgtaat 27 <210> 624 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 624 gagaggaatt caaactgagg ca 22 <210> 625 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 625 gagaggaatt caaactgagg catatgat 28 <210> 626 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 626 gaggctgaaa cagtgacctg t 21 <210> 627 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 627 gaggctgaaa cagtgacctg tcttggt 27 <210> 628 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 628 gtacatgaag caactccagt c 21 <210> 629 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 629 gtacatgaag caactccagt cccaaat 27 <210> 630 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 630 gacgggtggg gagagggaca c 21 <210> 631 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 631 gacgggtggg gagagggaca cacagat 27 <210> 632 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 632 gtcccaaata tgtagctgtt tg 22 <210> 633 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 633 gtcccaaata tgtagctgtt tgggaggt 28 <210> 634 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 634 ggccaggggt cactccagga t 21 <210> 635 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 635 ggccaggggt cactccagga ttccaat 27 <210> 636 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 636 gccagagccg gggtgtgcag ac 22 <210> 637 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 637 gccagagccg gggtgtgcag acggcagt 28 <210> 638 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 638 gaggacgtgt gtgtctgtgt gg 22 <210> 639 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 639 gaggacgtgt gtgtctgtgt gggtgagt 28 <210> 640 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 640 gggagaaggc caggggtcac tc 22 <210> 641 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 641 gggagaaggc caggggtcac tccaggat 28 <210> 642 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 642 gggtgagtga gtgtgtgcgt g 21 <210> 643 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 643 gggtgagtga gtgtgtgcgt gtggggt 27 <210> 644 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 644 gagtgaggac gtgtgtgtct gt 22 <210> 645 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 645 gagtgaggac gtgtgtgtct gtgtgggt 28 <210> 646 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 646 gcgttggagc ggggagaagg cc 22 <210> 647 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 647 gcgttggagc ggggagaagg ccaggggt 28 <210> 648 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 648 gctccattca cccagcttcc c 21 <210> 649 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 649 gctccattca cccagcttcc ctgtggt 27 <210> 650 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 650 cccaagaaga agaggaaagt c 21 <210> 651 <211> 76 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 651 gttttagagc tagaaatagc aagttaaaat aaggctagtc cgttatcaac ttgaaaaagt 60 ggcaccgagt cggtgc 76 <210> 652 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 652 tccagatggc acattgtcag 20 <210> 653 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 653 agggagcagg aaagtgaggt 20 <210> 654 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 654 gtagttgccg tcgtccttga a 21 <210> 655 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 655 gtagttgccg tcgtccttga agaagat 27 <210> 656 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 656 gccacctacg gcaagctgac cc 22 <210> 657 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 657 gccacctacg gcaagctgac cctgaagt 28 <210> 658 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 658 gacggcaact acaagacccg cgc 23 <210> 659 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 659 gacggcaact acaagacccg cgccgaggt 29 <210> 660 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 660 gagtccgagc agaagaagaa ggg 23 <210> 661 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 661 gagttagagc agaagaagaa agg 23 <210> 662 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 662 gagtctaagc agaagaagaa gag 23 <210> 663 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 663 gaggccgagc agaagaaaga cgg 23 <210> 664 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 664 gagtcctagc aggagaagaa gag 23 <210> 665 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 665 aagtctgagc acaagaagaa tgg 23 <210> 666 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 666 gagtccggga aggagaagaa agg 23 <210> 667 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 667 gaatccaagc aggagaagaa gga 23 <210> 668 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 668 acgtctgagc agaagaagaa tgg 23 <210> 669 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 669 ggtgagtgag tgtgtgcgtg tgg 23 <210> 670 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 670 agtgagtgag tgtgtgtgtg ggg 23 <210> 671 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 671 agagagtgag tgtgtgcatg agg 23 <210> 672 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 672 tgtgggtgag tgtgtgcgtg agg 23 <210> 673 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 673 gctgagtgag tgtatgcgtg tgg 23 <210> 674 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 674 tgtgggtgag tgtgtgcgtg aga 23 <210> 675 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 675 tgtgagtgag tgtgtgcgtg tga 23 <210> 676 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 676 ggtgagtgag tgcgtgcggg tgg 23 <210> 677 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 677 agtgtgtgag tgtgtgcgtg tgg 23 <210> 678 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 678 actgtgtgag tgtgtgcgtg agg 23 <210> 679 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 679 gaccccctcc accccgcctc cgg 23 <210> 680 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 680 attccccccc accccgcctc agg 23 <210> 681 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 681 acaccccccc accccgcctc agg 23 <210> 682 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 682 gggcccctcc accccgcctc tgg 23 <210> 683 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 683 cgccctcccc accccgcctc cgg 23 <210> 684 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 684 gacccccccc accccgcccc cgg 23 <210> 685 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 685 gcccccaccc accccgcctc tgg 23 <210> 686 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 686 ctccccaccc accccgcctc agg 23 <210> 687 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 687 tgcccctccc accccgcctc tgg 23 <210> 688 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 688 gggcacgggc agcttgcccg tga 23 <210> 689 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (21)..(26) <223> a, c, t, g, unknown or other <400> 689 gggcacgggc agcttgcccg nnnnnn 26 <210> 690 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (21)..(26) <223> a, c, t, g, unknown or other <400> 690 gtcgccctcg aacttcacct nnnnnn 26 <210> 691 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 691 gccacgaagc aggccaatgg ggag 24 <210> 692 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 692 gccacacagc aggtcaatgg ggaa 24 <210> 693 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 693 gaatcccttc tgcagcacct ggat 24 <210> 694 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 694 caatacctac tgcagcacct agag 24 <210> 695 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 695 ctgtcccctc cacagcacct ggag 24 <210> 696 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 696 aaatcccttc cgcagcacct aggt 24 <210> 697 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 697 taatcccttc cacagtacct agaa 24 <210> 698 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 698 gaaccccttc tacagcacct cggc 24 <210> 699 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 699 ttatcccttc tccagcacct agaa 24 <210> 700 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 700 gcggcggctg cacaaccagt ggag 24 <210> 701 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 701 tatgcggctg cacagccagt gggag 25 <210> 702 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 702 gtgggggcca cacaaccagt tgag 24 <210> 703 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 703 ggttgtgcag ccgccgctcc agag 24 <210> 704 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 704 ggtgcatttt caggaggaag cgat 24 <210> 705 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 705 ggtccatttt caggaggaag agtg 24 <210> 706 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 706 actgcatttt caggaggaac agag 24 <210> 707 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 707 gatgcatttc caggaggaag gagag 25 <210> 708 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 708 aatgcatttt cagaaggaag tgat 24 <210> 709 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 709 agtgcatcat caggaggaag ggaa 24 <210> 710 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 710 gacgcatctt caagaggaag tgaa 24 <210> 711 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 711 gctgcatgtc caggaggaag ggag 24 <210> 712 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 712 ggtccatgtt caggaggaaa ggag 24 <210> 713 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 713 ggtccatttc caggagaaag ggag 24 <210> 714 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 714 ggtgcactca caggaggaaa tgag 24 <210> 715 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 715 gtgatatagg gctagaggag agaa 24 <210> 716 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 716 gagctgcagg gctagaggga ggag 24 <210> 717 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 717 gagatgtagg gctagagggg tgag 24 <210> 718 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 718 gagatgtagg gagagaggga gagag 25 <210> 719 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 719 tgagagtagg gctagaggag ggag 24 <210> 720 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 720 gagatgttgg gccagagggg agaa 24 <210> 721 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 721 gagatgaaag gcaagagggg agag 24 <210> 722 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 722 agagtgtagg accagagggg tggg 24 <210> 723 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 723 ttagtgtagg gccagagagg gaag 24 <210> 724 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 724 gagatggagg gcaagagggg agaa 24 <210> 725 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 725 gaaatgtagg tctagagagg ggac 24 <210> 726 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 726 aagatgtatg actagaggga ggga 24 <210> 727 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 727 gagctgtagg gccaaaggga ggag 24 <210> 728 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 728 gagatatagg gcaagaggaa ggag 24 <210> 729 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 729 aaagtgcagg actaaagggg tgag 24 <210> 730 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 730 ctgatgtggg gctggagggg tgag 24 <210> 731 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 731 aagtggtagg attagagggg tgag 24 <210> 732 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 732 actgtgtagg cctagagagg tgag 24 <210> 733 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 733 gagatgtagt tctagaggga gagg 24 <210> 734 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 734 gtgatgtaga actagagggg tggg 24 <210> 735 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 735 gagttggagg cctagagagg ggag 24 <210> 736 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 736 gatgagtagg gctagaaggg ggag 24 <210> 737 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 737 aagatgaagg aatagagggg aaag 24 <210> 738 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 738 gggatggggg gctagaggag ggag 24 <210> 739 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 739 gtggtatagg gctagagggg agat 24 <210> 740 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 740 gaggtgcggg gcaaggggag ggag 24 <210> 741 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 741 gatatgtagg gccaaaggga agag 24 <210> 742 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 742 gtgatgtggg gctagagagt agaa 24 <210> 743 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 743 ggaatgtagg gccagagaga ggag 24 <210> 744 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 744 atgatgtagg tcaagagggg tgaa 24 <210> 745 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 745 tggatgtagg agtagagggt agag 24 <210> 746 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 746 gagaagcagg gctagaggag gagg 24 <210> 747 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 747 aagatgaagg gctaggggtg agag 24 <210> 748 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 748 gagatataag gctggagggg taag 24 <210> 749 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 749 aagatacagg gagagagggg agag 24 <210> 750 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 750 gaggactagg gctagaggga gggt 24 <210> 751 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 751 cagatgtagg gctgggggga gagg 24 <210> 752 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 752 cagatgtagg gctaaaatgg ggag 24 <210> 753 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 753 agtatatagg tctagagggg agag 24 <210> 754 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 754 aatatgtagg gaaagagggg ggaa 24 <210> 755 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 755 gagaggtagg gatagagggg agta 24 <210> 756 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 756 gaggagtagg ggtagagggg tgat 24 <210> 757 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 757 aagatgcaga gcaagagggg ggaa 24 <210> 758 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 758 aagatgcagg ggtagagggg tggg 24 <210> 759 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 759 aagctgtagg gccagatggg agag 24 <210> 760 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 760 gagctgcagg gctagggggg tgag 24 <210> 761 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 761 gagatgtagg accagaggga gggac 25 <210> 762 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 762 aagatgtcag gccagagggg taag 24 <210> 763 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 763 gagatgttgg gccagagggg agaa 24 <210> 764 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 764 gggttgcagg gccagagggg gagg 24 <210> 765 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 765 gagatgttgg gatagagggg gaaa 24 <210> 766 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 766 gaggggtagg actagagggg gaaa 24 <210> 767 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 767 gggatgtagg gctaggggga agac 24 <210> 768 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 768 gagatgaagt actagaaggg agag 24 <210> 769 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 769 cagatgtagg attagaggga gagaa 25 <210> 770 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 770 gaggtgtggg gctggagggg gaag 24 <210> 771 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 771 gagaggtagg gctggagggg agct 24 <210> 772 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 772 gcgagcagcg tcttcgagag tgag 24 <210> 773 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 773 ctgtggcaag agcttcagcc agag 24 <210> 774 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 774 gtgcggcaag agcttcagcc agag 24 <210> 775 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 775 tcgcagcaag agcttcagcc tgag 24 <210> 776 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 776 gtgcgggaag agcttcatcc agag 24 <210> 777 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 777 gtgtggcaag agcttcagca ggag 24 <210> 778 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 778 gtgtgggaag agcttcagcc agag 24 <210> 779 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 779 gtgcaacaag agctccagcc tgag 24 <210> 780 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 780 gtgcggcaag agcttcagcc gggg 24 <210> 781 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 781 atgtggtaag ggcttcagcc agag 24 <210> 782 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 782 atgtggtaag agcttcagcc agat 24 <210> 783 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 783 gtgtggcaag accttcagcc agac 24 <210> 784 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 784 ctgcggcaag tgcttcagct ggag 24 <210> 785 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 785 gtgcggcaag agcttcagcc agaa 24 <210> 786 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 786 gtgtggcaag accttcagcc ggac 24 <210> 787 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 787 gtgcggcaag agcttcagcc agtg 24 <210> 788 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 788 gtgtggcaag agcttcagca ggaa 24 <210> 789 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 789 gtgcggcaag agcttcagcc ggcg 24 <210> 790 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 790 gagcagcaag aacttcagcc caag 24 <210> 791 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 791 gtgtggcaag ggcttcagcc aggc 24 <210> 792 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 792 gtgcggcaag gccttcagcc agag 24 <210> 793 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 793 gtgcggcaag accttcaccc tgag 24 <210> 794 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 794 atgaggcaag aacataagcc tgag 24 <210> 795 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 795 gcagaaggga ttccatgagg tgcg 24 <210> 796 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 796 tgagaagaga tcccatgagg gaag 24 <210> 797 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 797 gaagggattc catgaggtgc gcg 23 <210> 798 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 798 atagggattc catgaggtgt gga 23 <210> 799 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 799 gggtgcattt tcaggaggaa gcg 23 <210> 800 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 800 gcagacggca gtcactaggg ggcg 24 <210> 801 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 801 acagaaggca gccactaggg aggcc 25 <210> 802 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 802 tcagacggtg gtcactagga ggcg 24 <210> 803 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 803 gcagaaaaca gccactaggg tgcc 24 <210> 804 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 804 gcagacgaca gtcactagga agcc 24 <210> 805 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 805 gctgggtgaa tggagcgagc agcg 24 <210> 806 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 806 gagttagagc agaagaagaa agg 23 <210> 807 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 807 gagtctaagc agaagaagaa gag 23 <210> 808 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 808 gaggccgagc agaagaaaga cgg 23 <210> 809 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 809 gagtcctagc aggagaagaa gag 23 <210> 810 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 810 aagtctgagc acaagaagaa tgg 23 <210> 811 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 811 gagtccggga aggagaagaa agg 23 <210> 812 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 812 gaatccaagc aggagaagaa gga 23 <210> 813 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 813 gtgtggcaag ggcttcagcc agg 23 <210> 814 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 814 gtgaggcagg agcatcagcc cgg 23 <210> 815 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 815 atggggaaag agcttcagcc tgg 23 <210> 816 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 816 gtgagggaag agcttcagca agg 23 <210> 817 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 817 atgtggtaag agcttcagcc aga 23 <210> 818 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 818 gtggggcaag aggttcagcc tgg 23 <210> 819 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 819 gtgcggcaag agcttcagcc aga 23 <210> 820 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 820 ctgtggcaag agcttcagcc aga 23 <210> 821 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 821 tcgcagcaag agcttcagcc tga 23 <210> 822 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 822 gtgctgcagg ggcttcagcc cgg 23 <210> 823 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 823 gtgtggcaag accttcagcc gga 23 <210> 824 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 824 gtgtggcaag agcttcagca gga 23 <210> 825 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 825 ttccggcagg agcttcagcc tgg 23 <210> 826 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 826 gtgtgacaag agcttcaaca ggg 23 <210> 827 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 827 gctgagtgag tgtatgcgtg tgg 23 <210> 828 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 828 tgtgggtgag tgtgtgcgtg agg 23 <210> 829 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 829 agtgagtgag tgtgtgtgtg ggg 23 <210> 830 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 830 agagagtgag tgtgtgcatg agg 23 <210> 831 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 831 gttgagtgaa tgtgtgcgtg agg 23 <210> 832 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 832 agtgaatgag tgtgtgtgtg tgg 23 <210> 833 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 833 ggtgagtgag tgcgtgcggg tgg 23 <210> 834 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 834 agcgagtggg tgtgtgcgtg ggg 23 <210> 835 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 835 agtgtgtgag tgtgtgcgtg tgg 23 <210> 836 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 836 tgtgagtaag tgtgtgtgtg tgg 23 <210> 837 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 837 actgtgtgag tgtgtgcgtg agg 23 <210> 838 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 838 ggtgagtgag tgtgtgtgtg agg 23 <210> 839 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 839 tgtgggtgag tgtgtgcgtg aga 23 <210> 840 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 840 ggtggatgag tgtgtgtgtg ggg 23 <210> 841 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 841 tgtgagtgag tgtgtgcgtg tga 23 <210> 842 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 842 agggagtgac tgtgtgcgtg tgg 23 <210> 843 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 843 ggtgtgtgag tgtgtgtgtg tgg 23 <210> 844 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 844 agcgagtgag tgtgtgtgtg ggg 23 <210> 845 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 845 tgtgggtgag catgtgcgtg agg 23 <210> 846 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 846 tgtgagtgag tgtgtgtatg ggg 23 <210> 847 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 847 agtgagaaag tgtgtgcatg cgg 23 <210> 848 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 848 ggtgagtaag tgtgagcgta agg 23 <210> 849 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 849 tgtgggtgag tgtgtgtgtg tgg 23 <210> 850 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 850 tgtgagtgag tgtgtgtgtg tga 23 <210> 851 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 851 agtgagtgag tgagtgagtg agg 23 <210> 852 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 852 gatgagtgag tgagtgagtg ggg 23 <210> 853 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 853 agtgagtaag tgagtgagtg agg 23 <210> 854 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 854 agtgagtatg tgtgtgtgtg ggg 23 <210> 855 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 855 gatgagtgtg tgtgtgtgtg agg 23 <210> 856 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 856 ggtgtgtgag tgtgagtgtg ggg 23 <210> 857 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 857 ggtgagtgtg tgtgtgcatg tgg 23 <210> 858 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 858 gatgagtcag tgagtgagtg ggg 23 <210> 859 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 859 ggtgagtcag tgtgtgagtg agg 23 <210> 860 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 860 agtgagtgag tatgtgtgta tgg 23 <210> 861 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 861 ggtgagtgag tgagtgagtg agg 23 <210> 862 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 862 tgtgagtgag tgtgtgtgtg tga 23 <210> 863 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 863 ggtgagagag tgtgtgcgta gga 23 <210> 864 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 864 ggagagtgag tgtgtgcatg tgc 23 <210> 865 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 865 tgtgagtggg tgtgtgcatg tgg 23 <210> 866 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 866 agtgagtgag tgtgtgtgtg aga 23 <210> 867 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 867 tgtgagtgag tgtgtgtgtg tga 23 <210> 868 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 868 aatgagtgag tgtgtgtgtg tga 23 <210> 869 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 869 ggtgagcaag tgtgtgtgtg tgg 23 <210> 870 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 870 ctggagtgag tgtgtgtgtg tgg 23 <210> 871 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 871 ggtgagtagg tgtgtgtgtg ggg 23 <210> 872 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 872 ggggtgtggg tgtgggggtg tg 22 <210> 873 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 873 cgtgagtgag tgtgtacctg ggg 23 <210> 874 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 874 gcaaccacaa acccacgagg gcagagt 27 <210> 875 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 875 acaaacacat acccacaagg acagagt 27 <210> 876 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 876 gcaatcacaa taccacaagg gaagagg 27 <210> 877 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (22)..(23) <223> a, c, t, g, unknown or other <400> 877 gtagggcctt cgcgcacctc anngrrt 27 <210> 878 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 878 gtagggcctt cgcgcacctc atggaat 27 <210> 879 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (22)..(23) <223> a, c, t, g, unknown or other <400> 879 gcaaggcccg gcgcacggtg gnngrrt 27 <210> 880 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 880 gcaaggcccg gcgcacggtg gcggggt 27 <210> 881 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 881 ctgaggcccg gcccacggtg gtgagga 27 <210> 882 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 882 acaaggctca gaacacggtg agaaagt 27 <210> 883 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 883 gcaaggcccc aggcatggtg gcacagt 27 <210> 884 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (22)..(23) <223> a, c, t, g, unknown or other <400> 884 gaaagagaga tgtagggcta gnngrrt 27 <210> 885 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 885 gaaagagaga tgtagggcta gaggggt 27 <210> 886 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 886 gaaagaggca tgtagggcta cagaggc 27 <210> 887 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 887 gaaagagaga aatagggcta gaacaaa 27 <210> 888 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (24)..(25) <223> a, c, t, g, unknown or other <400> 888 gtactcacct ctcatgaagc actnngrrt 29 <210> 889 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 889 gtactcacct ctcatgaagc actgtgggt 29 <210> 890 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 890 tacctcacct gccaggaagc acttgaaat 29 <210> 891 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 891 gggtgagtga gtgtgtgcgt gtggggt 27 <210> 892 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 892 gggtgagtca gtgagtgcgt ggtgagt 27 <210> 893 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 893 gagcgagtgg gtgtgtgcgt ggggggt 27 <210> 894 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 894 gggtgagtca gtgagtgcgt gatgagt 27 <210> 895 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 895 gagtgaatga gtgtgtgtgt gtggggt 27 <210> 896 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 896 gggtgagtca gtgtgtgagt ggtgagt 27 <210> 897 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 897 gggtgagtca gtgagtgcgt ggtgagt 27 <210> 898 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 898 gtgtgagtgt gtgtgtgcgt acagggt 27 <210> 899 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 899 gagtgagtga gtgtgtgtgt ggggggg 27 <210> 900 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 900 gggtgagtca gtgtgtgggt ggtgagt 27 <210> 901 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 901 gggtgagtca gtgtgtgagt ggtgagt 27 <210> 902 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 902 gggtgagtca gtgtgtgagt ggagagt 27 <210> 903 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 903 gggtgagtca gtgtgtgagt ggtgagt 27 <210> 904 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 904 gagtgagtaa gtgtgtgtgt gtgtggt 27 <210> 905 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 905 gggtgtgtgt ctgtgtgcgt gtggggt 27 <210> 906 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 906 gggtgagtca gtgtgtgagt ggtgagt 27 <210> 907 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 907 ggatgagtga gtgagtgagt ggggagt 27 <210> 908 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 908 gggtgagtca ctgtgtgagt ggtgagt 27 <210> 909 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 909 gggagagaga gtgtgtgcgt gtgtggt 27 <210> 910 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 910 ggctgaatgt gtgtgtgcgt gaatgat 27 <210> 911 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 911 aggtgaccgt gtgtgtgcgt ggagggt 27 <210> 912 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 912 gtatgggtga gagtgtgcgt gcacagt 27 <210> 913 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 913 gtgggtgtgg gggtgtgggt gttgggg 27 <210> 914 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 914 gggtgagtca gtgtgtgagt ggtgagt 27 <210> 915 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 915 gggtgagtca gtgtgtgagt ggtgagt 27 <210> 916 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 916 gaatgagtgt gtgtgtgtgt gtgcagt 27 <210> 917 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 917 gagtgagtgt gtgtgtgtga gagagag 27 <210> 918 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 918 ggatgagtga gtgagtgcat gttgagt 27 <210> 919 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 919 tggggtgtgg gtgtgtgggt gtggggg 27 <210> 920 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 920 gggtgagtga gtgagtgagt ggtgggt 27 <210> 921 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 921 gggtgagtga gtgagtgagt ggtgagt 27 <210> 922 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 922 gagtgagtca gtgtgtgagt ggtgagt 27 <210> 923 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 923 aagtgagtga gtgtgtgtgt gcaaaac 27 <210> 924 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 924 gaatgagtga gtgtgtgtgt aagaagt 27 <210> 925 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 925 gtgtgtgttg gggtgtgggt gtggggg 27 <210> 926 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 926 gtgtggtttc agaaccggag gatgaagc 28 <210> 927 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 927 gtgtggttcc agaaccggag gacaaagt 28 <210> 928 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 928 atctggttcc agaaccggag gatgaagt 28 <210> 929 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 929 atctggttcc agaaccgaag gatgaagt 28 <210> 930 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 930 gtgtggttcc agaaccgaag gatgaagt 28 <210> 931 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 931 atctggttcc agaaccggag gatgaagt 28 <210> 932 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 932 gtgtggttcc agaaccggcg gatgaagt 28 <210> 933 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 933 gtatggtttc agaaccgaag aacaaagt 28 <210> 934 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 934 atctggtttc agaaccggag gatgaagt 28 <210> 935 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 935 atctggttcc agaaccgcag gatgaagt 28 <210> 936 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 936 ttatggttcc agaaacgaag gaagcaat 28 <210> 937 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 937 ccaaggtccc ggaaccgaag gaggaagg 28 <210> 938 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 938 acgtggtacc agaatcggag gatgaagt 28 <210> 939 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 939 acctggttcc agaaccagag gatgaaat 28 <210> 940 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 940 gtatggcccc agaacagaag gaaagaat 28 <210> 941 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 941 gtctggttcc agaaccgaag ggccaagt 28 <210> 942 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 942 cctcagcctg agtgttgagg ctgcggt 27 <210> 943 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 943 gctcagcctg agtgttgagg ccccagt 27 <210> 944 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 944 gctgcagact gagtgttaag gccggagt 28 <210> 945 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 945 gttcagccca agtgttgaga ctcaggt 27 <210> 946 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 946 cttgagcctg ggtgtttgag gctgcagt 28 <210> 947 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 947 actgagcctg agggttgagg ctgcagt 27 <210> 948 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 948 acacagccag agggttgagg cggaggt 27 <210> 949 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 949 tatcagcttg agttttgagg ctgagat 27 <210> 950 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 950 cttgagccct gaatgttgag gctgcagt 28 <210> 951 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 951 tttgagccct gagtgttgag gctgcagt 28 <210> 952 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 952 ggctctccga ggagaaggcc aagtggt 27 <210> 953 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 953 ggctctccga tgggagggcc agagaat 27 <210> 954 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 954 ggctctctgg ggagaaagcc agggagc 27 <210> 955 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 955 ggctctcaga ggagaaggcc gagggga 27 <210> 956 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 956 agttctccaa ggagaagacc acgtggt 27 <210> 957 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 957 aactctccca ggagaaggcc cagaaat 27 <210> 958 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 958 gcgcccactg caaggcccgg cgcacggt 28 <210> 959 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 959 gcgcccactg cagggcccgg ctgcggag 28 <210> 960 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 960 gtgcccaccc agggcccggc acagagt 27 <210> 961 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 961 aggcccactg caaggcccag tgggcggc 28 <210> 962 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 962 gtgcccaccc agggcccggc acagagt 27 <210> 963 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <400> 963 ggggtcccag gtgctgacgt aggtagt 27 <210> 964 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (22)..(29) <223> a, c, t, g, unknown or other <400> 964 ggggcacggg cagcttgccc gnnnnnnnn 29 <210> 965 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> modified_base <222> (22)..(29) <223> a, c, t, g, unknown or other <400> 965 ggtcgccctc gaacttcacc tnnnnnnnn 29 <210> 966 <211> 5 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic peptide <400> 966 Ile Ile Lys Lys Gly 1 5 <210> 967 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 967 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Arg Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 968 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 968 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Arg Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Lys Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 His Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Asn Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 969 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 969 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Glu Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Met Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Met Ala Ser Phe 260 265 270 Tyr Lys Asn Asp Leu Ile Lys Phe Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 His Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 970 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 970 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asn Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ser Ser Phe 260 265 270 Tyr Ser Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 His Ile Ile Lys Arg Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 971 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 971 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Val Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 His Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Glu Ile Ile Lys Lys Gly 355 <210> 972 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 972 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Arg Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 His Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 973 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 973 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Phe Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asn Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Gly Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 His Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 974 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 974 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Lys Asp Lys Arg Pro Pro 305 310 315 320 His Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Ile Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 975 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 975 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu His Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 His Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Asn Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 976 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 976 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Asn Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 His Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys Arg 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 977 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 977 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Leu Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Arg Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn His Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 978 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 978 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Lys Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Thr Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Val Lys Lys Gly 355 <210> 979 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 979 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Arg Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Tyr Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Thr Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys Gln 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 980 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 980 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Leu Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 981 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 981 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Ile Tyr Lys Phe Val Thr Val Lys Asn Met Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Ile Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 982 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 982 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Arg Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Val Ile Lys Lys Gly 355 <210> 983 <211> 357 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 983 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Arg Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Asp Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Ile Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Arg Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Tyr Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys 355 <210> 984 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 984 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Thr Lys Lys Gly 355 <210> 985 <211> 356 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 985 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Gln Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Asn Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Asn Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile 355 <210> 986 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 986 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Tyr Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Ile Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Val Lys Lys Gly 355 <210> 987 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 987 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 988 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 988 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Lys Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 989 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 989 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Leu Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Met Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr His Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 His Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 990 <211> 353 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 990 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Ile Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Tyr Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Ser Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro <210> 991 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 991 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Asn Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 992 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 992 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Leu Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Lys Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Cys 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 993 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 993 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Lys Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Gly Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Asp Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Leu Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Val Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 994 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 994 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Ile Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Lys Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Asn Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 995 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 995 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Ile Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 996 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 996 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Gln Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Tyr 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Lys Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro His Ile Ile Lys Lys Gly 355 <210> 997 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 997 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Ile Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Arg Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 998 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 998 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Phe Glu Asn Met Asn Val Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 999 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 999 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys His Asn Arg Glu Leu Val Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Thr Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 1000 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 1000 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Met Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Glu Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Arg Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 1001 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 1001 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Val Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Asn Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Tyr Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Arg Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Arg Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 1002 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 1002 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Asn Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Ile Asn Gly Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Thr Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 1003 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 1003 Asn Asn Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Glu Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Ile Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Gly Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Ile Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Asn Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 1004 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 1004 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Val Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Ile Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Val Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Ile Lys Gly 355 <210> 1005 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 1005 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Gly Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 1006 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 1006 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ser Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys His Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Ile Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Thr Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Pro Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 1007 <211> 353 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 1007 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Glu Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Ser Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Tyr 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro <210> 1008 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 1008 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro Tyr 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Arg Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 1009 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 1009 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Asn Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Arg Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Phe Lys Tyr Ser His Met 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Ile Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 1010 <211> 353 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 1010 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Ile Arg Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro <210> 1011 <211> 353 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 1011 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Val Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Ile Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro <210> 1012 <211> 353 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 1012 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro <210> 1013 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 1013 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Met Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asp Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 His Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Gln Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 1014 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 1014 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Gly Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Arg Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Ser Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Thr Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 1015 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 1015 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Thr Asn Lys 115 120 125 Ser Pro Gly Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala Tyr Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Asn Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Glu Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 His Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 1016 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 1016 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Phe Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Asp Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Thr Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 1017 <211> 357 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 1017 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys His Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Glu Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asp Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys 355 <210> 1018 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 1018 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Asn Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Tyr Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 1019 <211> 359 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic polypeptide <400> 1019 Asn Lys Gly Tyr Lys His His Ala Glu Asp Ala Leu Ile Ile Ala Asn 1 5 10 15 Ala Asp Phe Ile Phe Lys Glu Trp Lys Lys Leu Asp Lys Ala Lys Lys 20 25 30 Val Met Glu Asn Gln Met Phe Glu Glu Lys Gln Ala Glu Ser Met Pro 35 40 45 Glu Ile Glu Thr Glu Gln Glu Tyr Lys Glu Ile Phe Ile Thr Pro His 50 55 60 Gln Ile Lys His Ile Lys Asp Phe Lys Asp Tyr Lys Tyr Ser His Arg 65 70 75 80 Val Asp Lys Lys Pro Asn Arg Lys Leu Ile Asn Asp Thr Leu Tyr Ser 85 90 95 Thr Arg Lys Asp Asp Lys Gly Asn Thr Leu Ile Val Asn Asn Leu Asn 100 105 110 Gly Leu Tyr Asp Lys Asp Asn Asp Lys Leu Lys Lys Leu Ile Asn Lys 115 120 125 Ser Pro Glu Lys Leu Leu Met Tyr His His Asp Pro Gln Thr Tyr Gln 130 135 140 Lys Leu Lys Leu Ile Met Glu Gln Tyr Gly Asp Glu Lys Asn Pro Leu 145 150 155 160 Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn Tyr Leu Thr Lys Tyr Ser Lys 165 170 175 Lys Asp Asn Gly Pro Val Ile Lys Lys Ile Lys Tyr Tyr Gly Asn Lys 180 185 190 Leu Asn Ala His Leu Asp Ile Thr Asp Asp Tyr Pro Asn Ser Arg Asn 195 200 205 Lys Val Val Lys Leu Ser Leu Lys Pro Tyr Arg Phe Asp Val Tyr Leu 210 215 220 Asp Asn Gly Val Tyr Lys Phe Val Thr Val Lys Asn Leu Asp Val Ile 225 230 235 240 Lys Lys Glu Asn Tyr Tyr Glu Val Asn Ser Lys Cys Tyr Glu Glu Ala 245 250 255 Lys Lys Leu Lys Lys Ile Ser Asn Gln Ala Glu Phe Ile Ala Ser Phe 260 265 270 Tyr Asn Asn Asp Leu Ile Lys Ile Asn Gly Glu Leu Tyr Arg Val Ile 275 280 285 Gly Val Asn Asn Asp Leu Leu Asn Arg Ile Glu Val Asn Met Ile Asp 290 295 300 Ile Thr Tyr Arg Glu Tyr Leu Glu Asn Met Asn Asp Lys Arg Pro Pro 305 310 315 320 Gln Ile Ile Lys Thr Ile Ala Ser Lys Thr Gln Ser Ile Lys Lys Tyr 325 330 335 Ser Thr Asp Ile Leu Gly Asn Leu Tyr Glu Val Lys Ser Lys Lys His 340 345 350 Pro Gln Ile Ile Lys Lys Gly 355 <210> 1020 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> misc_feature <222> (1)..(23) <223> This region may encompass 21-23 nucleotides <220> <221> modified_base <222> (1)..(25) <223> a, c, t, g, unknown or other <400> 1020 nnnnnnnnnn nnnnnnnnnn nnnnnarrt 29 <210> 1021 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic oligonucleotide <220> <221> misc_feature <222> (1)..(23) <223> This region may encompass 21-23 nucleotides <220> <221> modified_base <222> (1)..(25) <223> a, c, t, g, unknown or other <400> 1021 nnnnnnnnnn nnnnnnnnnn nnnnngrrt 29

Claims (36)

  1. 하기 위치: G1104, S1109, L1111, D1135, S1136, G1218, N1317, R1335, T1337 중 하나 이상에서 돌연변이를 갖는 단리된 스트렙토코쿠스 피오게네스(Streptococcus pyogenes) Cas9 (SpCas9) 단백질.
  2. 제1항에 있어서, 서열식별번호:1의 아미노산 서열과 적어도 80% 동일한 서열을 포함하는 단리된 단백질.
  3. 제1항에 있어서, 하기 돌연변이: G1104K; S1109T; L1111H; D1135V; D1135E; D1135N; D1335Y; S1136N; G1218R; N1317K; R1335E; R1335Q 및 T1337R 중 하나 이상을 포함하는 단리된 단백질.
  4. 제1항 내지 제3항 중 어느 한 항에 있어서, 하기 돌연변이: D1135E (D1135E 변이체); D1135V/R1335Q/T1337R (VQR 변이체); D1135V/G1218R/R1335Q/T1337R (VRQR 변이체); D1135E/R1335Q/T1337R (EQR 변이체); D1135N/G1218R/R1335Q/T1337R (NRQR 변이체); D1135Y/G1218R/R1335Q/T1337R (YRQR 변이체); G1104K/D1135V/G1218R/R1335Q/T1337R (KVRQR 변이체); S1109T/D1135V/G1218R/R1335Q/T1337R (TVRQR 변이체); L1111H/D1135V/G1218R/R1335Q/T1337R (HVRQR 변이체); D1135V/S1136N/G1218R/R1335Q/T1337R (VNRQR 변이체); D1135V/G1218R/N1317K/R1335Q/T1337R (VRKQR 변이체) 또는 D1135V/G1218R/R1335E/T1337R (VRER 변이체)을 포함하는 단리된 단백질.
  5. 제1항에 있어서, D10, E762, D839, H983 또는 D986에서의 돌연변이; 및 H840 또는 N863에서의 돌연변이로 이루어진 군으로부터 선택된, 뉴클레아제 활성을 감소시키는 하나 이상의 돌연변이를 추가로 포함하는 단리된 단백질.
  6. 제5항에 있어서, 돌연변이가
    (i) D10A 또는 D10N, 및
    (ii) H840A, H840N 또는 H840Y인
    단리된 단백질.
  7. 하기 위치: E782, N968 및/또는 R1015 중 하나 이상에서 돌연변이를 갖는 단리된 스타필로코쿠스 아우레우스(Staphylococcus aureus) Cas9 (SaCas9) 단백질.
  8. 제7항에 있어서, 서열식별번호:2의 아미노산 서열과 적어도 80% 동일한 서열을 포함하는 단리된 단백질.
  9. 제7항에 있어서, 하기 돌연변이: R1015Q, R1015H, E782K, N968K, E735K, K929R, A1021T, K1044N, E782K/N968K/R1015H (KKH 변이체); E782K/K929R/R1015H (KRH 변이체) 또는 E782K/K929R/N968K/R1015H (KRKH 변이체) 중 하나 이상을 포함하는 단리된 단백질.
  10. 제7항에 있어서, D10, D556, H557 및/또는 N580에서의 돌연변이로 이루어진 군으로부터 선택된, 뉴클레아제 활성을 감소시키는 하나 이상의 돌연변이를 추가로 포함하는 단리된 단백질.
  11. 제7항에 있어서, 돌연변이가 D10A, D556A, H557A, N580A, 예를 들어 D10A/H557A 및/또는 D10A/D556A/H557A/N580A인 단리된 단백질.
  12. 임의적인 개재 링커로 이종 기능적 도메인에 융합된 제1항 내지 제11항 중 어느 한 항의 단리된 단백질을 포함하는 융합 단백질이며, 여기서 링커는 융합 단백질의 활성을 방해하지 않는 것인 융합 단백질.
  13. 제12항에 있어서, 이종 기능적 도메인이 전사 활성화 도메인인 융합 단백질.
  14. 제12항에 있어서, 전사 활성화 도메인이 VP64 또는 NF-κB p65로부터의 것인 융합 단백질.
  15. 제12항에 있어서, 이종 기능적 도메인이 전사 사일런서 또는 전사 저해 도메인인 융합 단백질.
  16. 제15항에 있어서, 전사 저해 도메인이 크뤼펠-연관된 박스 (KRAB) 도메인, ERF 저해인자 도메인 (ERD), 또는 mSin3A 상호작용 도메인 (SID)인 융합 단백질.
  17. 제15항에 있어서, 전사 사일런서가 이질염색질 단백질 1 (HP1)인 융합 단백질.
  18. 제12항에 있어서, 이종 기능적 도메인이 DNA의 메틸화 상태를 변형시키는 효소인 융합 단백질.
  19. 제18항에 있어서, DNA의 메틸화 상태를 변형시키는 효소가 DNA 메틸트랜스퍼라제 (DNMT) 또는 TET 단백질인 융합 단백질.
  20. 제19항에 있어서, TET 단백질이 TET1인 융합 단백질.
  21. 제12항에 있어서, 이종 기능적 도메인이 히스톤 서브유닛을 변형시키는 효소인 융합 단백질.
  22. 제12항에 있어서, 히스톤 서브유닛을 변형시키는 효소가 히스톤 아세틸트랜스퍼라제 (HAT), 히스톤 데아세틸라제 (HDAC), 히스톤 메틸트랜스퍼라제 (HMT) 또는 히스톤 데메틸라제인 융합 단백질.
  23. 제12항에 있어서, 이종 기능적 도메인이 생물학적 테더인 융합 단백질.
  24. 제23항에 있어서, 생물학적 테더가 MS2, Csy4 또는 람다 N 단백질인 융합 단백질.
  25. 제12항에 있어서, 이종 기능적 도메인이 FokI인 융합 단백질.
  26. 제1항 내지 제25항 중 어느 한 항의 단백질을 코딩하는 단리된 핵산.
  27. 제26항의 단리된 핵산을 포함하는 벡터.
  28. 제27항에 있어서, 제21항의 단리된 핵산이 하기 위치: G1104, S1109, L1111, D1135, S1136, G1218, N1317, R1335, T1337 중 하나 이상에서 돌연변이를 갖는 단리된 스트렙토코쿠스 피오게네스 Cas9 (SpCas9) 단백질을 발현하기 위해 하나 이상의 조절 도메인에 작동가능하게 연결된 것인 벡터.
  29. 제27항에 있어서, 제21항의 단리된 핵산이 하기 위치: E782, N968 및/또는 R1015 중 하나 이상에서 돌연변이를 갖는 단리된 스타필로코쿠스 아우레우스 Cas9 (SaCas9) 단백질을 발현하기 위해 하나 이상의 조절 도메인에 작동가능하게 연결된 것인 벡터.
  30. 제26항의 핵산을 포함하고, 임의적으로 제1항 내지 제25항 중 어느 한 항의 단백질을 발현하는 숙주 세포, 바람직하게는 포유동물 숙주 세포.
  31. 세포의 게놈을 변경시키는 방법이며, 제1항 내지 제25항 중 어느 한 항의 단리된 단백질 또는 융합 단백질, 및 세포의 게놈의 선택된 부분에 상보적인 영역을 갖는 가이드 RNA를 세포에서 발현시키거나 또는 세포와 접촉시키는 것을 포함하는 방법.
  32. 제31항에 있어서, 단리된 단백질 또는 융합 단백질이 핵 국재화 서열, 세포 침투 펩티드 서열 및/또는 친화성 태그 중 하나 이상을 포함하는 것인 방법.
  33. 제31항에 있어서, 세포가 줄기 세포인 방법.
  34. 제33항에 있어서, 세포가 배아 줄기 세포, 중간엽 줄기 세포 또는 유도된 만능 줄기 세포이거나; 살아있는 동물에 있거나; 또는 배아에 있는 것인 방법.
  35. 이중 가닥 DNA (dsDNA) 분자를 변경시키는 방법이며, 제1항 내지 제25항 중 어느 한 항의 단리된 단백질 또는 융합 단백질, 및 dsDNA 분자의 선택된 부분에 상보적인 영역을 갖는 가이드 RNA를 dsDNA 분자와 접촉시키는 것을 포함하는 방법.
  36. 제35항에 있어서, dsDNA 분자가 시험관내에 있는 것인 방법.
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