KR20210035806A - 가용화된 아피라제, 방법 및 용도 - Google Patents
가용화된 아피라제, 방법 및 용도 Download PDFInfo
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- KR20210035806A KR20210035806A KR1020217001187A KR20217001187A KR20210035806A KR 20210035806 A KR20210035806 A KR 20210035806A KR 1020217001187 A KR1020217001187 A KR 1020217001187A KR 20217001187 A KR20217001187 A KR 20217001187A KR 20210035806 A KR20210035806 A KR 20210035806A
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Abstract
본 발명은 가용화된 아피라제 폴리펩티드의 설계 및 치료적 용도, 제약 조성물, 치료적 용도 및 조직 손상의 예방 및 치료에 유용한 방법에 관한 것이다.
Description
본 발명은 가용화된 아피라제 폴리펩티드의 설계 및 치료적 용도, 제약 조성물, 및 조직 손상의 예방 및 치료에 유용한 방법에 관한 것이다.
아피라제(ATP-디포스파타제, 아데노신 디포스파타제, ADP 분해효소, 또는 ATP 디포스포하이드롤라제)는 디- 및 트리포스페이트 뉴클레오티드(NDP 및 NTP) 둘 다에 대해 활성인 원형질막 결합 효소군으로, 2개의 별개의 연속적인 포스페이트 방출 단계에서 NTP를 뉴클레오티드 모노포스페이트(NMP)로 가수분해하고, NDP는 중간체이다. 세포 표면에서 발견되고 세포 외 뉴클레오티드를 가수분해하는 대부분의 엑토-ATP 분해효소는 이 효소 패밀리에 속한다. 이들은 ATP와 ADP 둘 다를 가수분해함으로써, 특히 ATP를 가수분해하는 ATP 분해효소와 상이하다.
분화 클러스터 39(CD39, UniProt P49961, 또는 서열번호 1)로도 알려져 있는, 최초로 알려진 인간 아피라제인 엑토뉴클레오시드 트리포스페이트 디포스포하이드롤라제-1(유전자: ENTPD1, 단백질: NTPDase1)는 세포 외로 향하는 촉매 부위를 갖는 세포 표면에 위치한 효소이다.
공지된 인간 CD39 패밀리 가운데, 구성원 CD39L3은 CD39와 CD39L1 (엑토-ATP 분해효소) 사이의 생화학적 활성을 갖는, 엑토-아피라제(엑토-ATPD 분해효소)로 알려져 있다. 구체적으로 예를 들어, US7247300B1(본원에 참조로 포함됨)에 개시되었거나 본원에 서열번호 3으로 포함된 바와 같은 인간 CD39L3이 가용화되어 치료 목적을 위해 정제되었다.
본 개시는 특히 가용화된 인간 아피라제, 예컨대 인간 CD39의 특정 변형이 놀랍도록 활성인 단백질을 초래하며, 이는 여전히 안전하고 제조가 용이하다는 예상치 못한 발견을 기초로 한다.
본 발명의 제1 양태에 따르면, N 말단 결실, C 말단 결실 및 중심 변형으로 구성된 목록으로부터 선택된 적어도 2종의 변형이 있는 가용화된 인간 아피라제가 제공된다.
일 구현예에서 가용화된 인간 아피라제는 N 말단 결실, C 말단 결실 및 변형 결실을 포함한다.
일 구현예에서, 중심 변형은 1개 이상의 아미노산의 결실을 포함한다. 또 다른 구현예에서, 중심 변형은 1개 이상의 아미노산의 점 돌연변이, 예컨대 치환 돌연변이를 포함한다. 또 다른 구현예에서, 중심 변형은 1개 이상의 아미노산의 결실 및 1개 이상의 아미노산의 점 돌연변이, 예컨대, 치환 돌연변이의 조합이다.
N 말단 결실은 서열번호 1에 따른 야생형 CD39 서열의 N 말단으로부터 결실된 30 내지 50개의 아미노산, 예컨대, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 또는 50개의 아미노산의 결실일 수 있다. 바람직한 구현예에서, N 말단 결실은 34, 37, 38 또는 45개의 아미노산이다.
C 말단 결실은 서열번호 1에 따른 야생형 CD39 서열의 C 말단으로부터 결실된 20 내지 40개의 아미노산, 예컨대, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39 또는 40개의 아미노산의 결실일 수 있다. 바람직한 구현예에서, C 말단 결실은 22, 29 또는 37개의 아미노산이다.
중심 결실은 서열번호 1에 따른 야생형 CD39 서열로부터 결실된, 10 내지 15개의 연속적인 아미노산, 예컨대, 10, 11, 12, 13, 14 또는 15개의 아미노산의 결실일 수 있다. 바람직한 구현예에서, 중심 결실은 12개의 아미노산, 예컨대, 서열번호 1에 따른 야생형 CD39 서열과 관련하여 아미노산 번호 193 내지 204이다.
일 구현예에서, 가용화된 인간 아피라제는 K71E, N73Q, V95A, G102D, Y104S, T106S, R113M, L149M, V151A, E173D, T229A, L254M, K258R, W263R, E276D, N292Q, R304G, I319T, N327Q, A362N, F365S, N371Q, K405N, Y412F, L424Q, H436D, I437N, F439S, G441D, N457Q, P463S, 및 S469R로 구성된 군으로부터 선택된, 서열번호 1에 따른 야생형 CD39 서열과 관련하여 1, 2, 3, 4, 또는 5개의 점 돌연변이를 포함한다.
일 구현예에서 가용화된 인간 아피라제는 서열번호 4, 서열번호 6, 서열번호 32, 서열번호 54, 서열번호 56, 서열번호 70, 서열번호 76, 및 서열번호 78로 구성된 군으로부터 선택된 서열을 포함한다.
일 구현예에서, 가용화된 인간 아피라제는 서열번호 131, 서열번호 133, 서열번호 135, 서열번호 137, 서열번호 139 및 서열번호 141로 구성된 군으로부터 선택된 서열을 포함한다.
일 특정 구현예에서, 가용화된 인간 아피라제는 서열번호 213, 서열번호 227, 서열번호 219, 서열번호 227, 서열번호 217, 서열번호 209, 서열번호 221, 서열번호 72, 서열번호 215, 서열번호 223, 서열번호 211, 서열번호 58 및 서열번호 229로 구성된 군으로부터 선택된 서열을 포함한다.
일 특정 구현예에서, 가용화된 인간 아피라제는 서열번호 213, 서열번호 227, 서열번호 219, 서열번호 227, 서열번호 217, 서열번호 209, 서열번호 221, 서열번호 72, 서열번호 215, 서열번호 223, 서열번호 211, 서열번호 58 및 서열번호 229로 구성된 군으로부터 선택된 서열로 구성된다.
바람직한 구현예에서, 가용화된 인간 아피라제는 서열번호 58, 서열번호 72 및 서열번호 229로 구성된 군으로부터 선택된 서열을 포함한다.
일 구현예에서, 가용화된 인간 아피라제는 서열번호 58을 포함한다. 일 구현예에서, 가용화된 인간 아피라제는 서열번호 72를 포함한다. 일 구현예에서, 가용화된 인간 아피라제는 서열번호 229를 포함한다.
바람직한 구현예에서, 가용화된 인간 아피라제는 서열번호 58, 서열번호 72 및 서열번호 229로 구성된 군으로부터 선택된 서열로 구성된다.
일 구현예에서, 가용화된 인간 아피라제는 서열번호 58로 구성된다. 일 구현예에서, 가용화된 인간 아피라제는 서열번호 72로 구성된다. 일 구현예에서, 가용화된 인간 아피라제는 서열번호 229로 구성된다.
본 발명의 제2 양태에 따르면, 본 발명의 제1 양태에 따른 아피라제의 치료 유효 용량 및 1종 이상의 제약상 허용 가능한 담체를 포함하는 제약 조성물이 제공된다.
일 구현예에서, 제약 조성물은 1종 이상의 추가 활성 성분을 추가로 포함한다.
본 발명의 제3 양태에 따르면, 의약으로서 사용하기 위한 제1 양태에 따른 단리된 아피라제가 제공된다.
본 발명의 제4 양태에 따르면, 조직 손상의 치료에 사용하기 위한 제1 양태에 따른 단리된 아피라제가 제공된다.
조직 손상은 급성 뇌 손상(뇌졸중); 급성 다기관 부전; 신장 또는 기타 고형 장기 이식 후 지연 이식편 기능; 화상 손상; 방사선 손상; 외상 및/또는 저산소증으로 인한 급성 손상, 예컨대 급성 호흡 곤란 증후군(ARDS) 또는 폐 손상; 급성 신장 손상, 예컨대 흉부 수술(예를 들어, 대동맥 판막 교체, 관상 동맥 우회 수술) 또한 패혈증 또는 횡문근 융해증 또는 항생제 또는 기타 약물의 독성 효과에 따른 급성 신장 손상; 급성 심근 손상일 수 있다.
또 다른 구현예에서, 본 개시의 제4 양태는 심장 수술 관련 급성 신장 손상의 치료에 사용하기 위한 본 발명의 제1 양태에 따른 단리된 아피라제에 관한 것이다.
또 다른 구현예에서, 본 개시의 제4 양태는 지연 이식편 기능(DGF), 급성 호흡 곤란 증후군(ARDS), 급성 심근 경색(AMI), 외상성 뇌 손상(TBI)/급성 허혈 뇌졸중(AIS), 허혈-재관류 손상(IRI), 또는 종종 다기관 부전(MOF)으로 지칭되는 이들의 조합의 치료에 사용하기 위한 본 발명의 제1 양태에 따른 단리된 아피라제에 관한 것이다.
일 구현예에서, 심장 수술 관련 급성 신장 손상의 치료에 사용되는 가용화된 인간 아피라제는 서열번호 58의 아미노산 서열을 포함한다.
일 구현예에서, 심장 수술 관련 급성 신장 손상의 치료에 사용되는 가용화된 인간 아피라제는 서열번호 72의 아미노산 서열을 포함한다. 일 구현예에서, 심장 수술 관련 급성 신장 손상의 치료에 사용되는 가용화된 인간 아피라제는 서열번호 229의 아미노산 서열을 포함한다.
추가의 바람직한 구현예에서, 본 개시는 패혈증 관련 급성 신장 손상의 치료를 위한 본 발명의 제1 양태에 따른 단리된 아피라제의 용도에 관한 것이다.
제4 양태의 일 구현예에서, 패혈증 관련 급성 신장 손상의 치료에 사용하기 위한 가용화된 인간 아피라제는 서열번호 58의 아미노산 서열을 포함한다.
제4 양태의 일 구현예에서, 패혈증 관련 급성 신장 손상의 치료에 사용하기 위한 가용화된 인간 아피라제는 서열번호 72의 아미노산 서열을 포함한다.
제4 양태의 일 구현예에서, 패혈증 관련 급성 신장 손상의 치료에 사용하기 위한 가용화된 인간 아피라제는 서열번호 229의 아미노산 서열을 포함한다.
본 발명의 제5 양태에 따르면, 인간 대상체에서 조직 손상의 치료 방법이 제공되며, 방법은 상기 대상체에게 제1 양태에 따른 가용화된 인간 아피라제의 치료 유효 용량을 투여하는 단계를 포함한다. 본 발명의 제5 양태의 일 구현예는 심장 수술 관련 급성 신장 손상의 치료 방법에 관한 것으로, 방법은 이러한 치료를 필요로 하는 대상체에게 본 발명의 제1 양태에 따른 단리된 아피라제의 치료 유효 용량을 투여하는 단계를 포함한다.
본 발명의 제5 양태의 또 다른 구현예는 지연 이식편 기능(DGF), 급성 호흡 곤란 증후군(ARDS), 급성 심근 경색(AMI), 외상성 뇌 손상(TBI)/급성 허혈 뇌졸중(AIS), 허혈-재관류 손상(IRI), 또는 종종 다기관 부전(MOF)으로 지칭되는 이들의 조합의 치료 방법에 관한 것으로, 방법은 이러한 치료를 필요로 하는 대상체에게 본 발명의 제1 양태에 따른 단리된 아피라제의 치료 유효 용량을 투여하는 단계를 포함한다.
제5 양태의 일 구현예에서, 심장 수술 관련 급성 신장 손상의 치료 방법에 사용되는 가용화된 인간 아피라제는 서열번호 58, 서열번호 72 또는 서열번호 229의 아미노산 서열을 포함한다.
본 발명의 제5 양태의 일 구현예는 패혈증 관련 급성 신장 손상의 치료 방법에 관한 것으로, 방법은 이러한 치료를 필요로 하는 대상체에게 본 발명의 제1 양태에 따른 단리된 아피라제의 치료 유효 용량을 투여하는 단계를 포함한다.
제5 양태의 일 구현예에서, 패혈증 관련 급성 신장 손상의 치료 방법에 사용되는 가용화된 인간 아피라제는 서열번호 58, 서열번호 72 또는 서열번호 229의 아미노산 서열을 포함한다. 조직 손상은 급성 뇌 손상(뇌졸중); 급성 다기관 부전; 신장 또는 기타 고형 장기 이식 후 지연 이식편 기능; 화상 손상; 방사선 손상; 외상 및/또는 저산소증으로 인한 급성 손상, 예컨대 급성 호흡 곤란 증후군(ARDS) 또는 폐 손상; 급성 신장 손상, 예컨대 흉부 수술(예를 들어, 대동맥 판막 교체, 관상 동맥 우회 수술) 또한 패혈증 또는 횡문근 융해증 또는 항생제 또는 기타 약물의 독성 효과에 따른 급성 신장 손상; 급성 심근 손상일 수 있다.
본 발명의 제6 양태에 따르면, 제1 양태에 따른 임의의 아피라제를 암호화하는 단리된 핵산 분자가 제공된다.
본 발명의 제7 양태에 따르면, 제6 양태에 따른 1개 이상의 핵산 서열을 포함하는 클로닝 또는 발현 벡터가 제공되며, 이때, 벡터는 제1 양태에 따른 단리된 아피라제의 재조합 생산에 적합하다.
본 발명의 제8 양태에 따르면, 제7 양태에 따른 1개 이상의 클로닝 또는 발현 벡터를 포함하는 숙주 세포가 제공된다.
본 발명의 제9 양태에 따르면, 제1 양태에 따른 아피라제의 생산 공정이 제공되며, 이는 제8 양태에 따른 숙주 세포를 배양하는 단계, 정제하는 단계, 및 상기 아피라제를 회수하는 단계를 포함한다.
도 1은 서열 정렬이다.
도 2a는 일 구현예에 따른 항-APP 웨스턴 블롯에 의한 인간 CD39를 함유하는 상청액의 발현 수준을 나타낸 것이다.
도 2b는 일 구현예에 따른 항-APP 웨스턴 블롯에 의한 시스테인 가교 결실 인간 CD39 변이체를 함유하는 상청액의 발현 수준을 나타낸 것이다.
도 3은 CD39 변이체의 고체상 ATP 분해효소 분석 결과를 보여주는 그래프이다.
도 4는 일 구현예에 따른 인간 CD39 변이체로 형질전환된 HEK293 세포에서의 고체상 ATP 절단을 보여주는 그래프이다.
도 5는 일 구현예에 따른 벡터의 개략적 개요이다.
도 6은 정상 상태 근사를 기초로 한 효소 모델이다.
도 7은 일 구현예에 따른 단백질에 대한 동역학 데이터 및 모델 적합의 개요이다.
도 8은 일 구현예에 따른 단백질에 대한 동역학 데이터 및 모델 적합의 개요이다.
도 9는 일 구현예에 따른 단백질에 대한 동역학 데이터 및 모델 적합의 개요이다.
도 10은 실험 조건의 개략도이다.
도 11은 구현예에 따른 단백질에 대한 AMP 수준을 보여주는 그래프이다.
도 12는 구현예에 따른 단백질에 대한 생체 내 결과를 보여주는 그래프이다.
도 2a는 일 구현예에 따른 항-APP 웨스턴 블롯에 의한 인간 CD39를 함유하는 상청액의 발현 수준을 나타낸 것이다.
도 2b는 일 구현예에 따른 항-APP 웨스턴 블롯에 의한 시스테인 가교 결실 인간 CD39 변이체를 함유하는 상청액의 발현 수준을 나타낸 것이다.
도 3은 CD39 변이체의 고체상 ATP 분해효소 분석 결과를 보여주는 그래프이다.
도 4는 일 구현예에 따른 인간 CD39 변이체로 형질전환된 HEK293 세포에서의 고체상 ATP 절단을 보여주는 그래프이다.
도 5는 일 구현예에 따른 벡터의 개략적 개요이다.
도 6은 정상 상태 근사를 기초로 한 효소 모델이다.
도 7은 일 구현예에 따른 단백질에 대한 동역학 데이터 및 모델 적합의 개요이다.
도 8은 일 구현예에 따른 단백질에 대한 동역학 데이터 및 모델 적합의 개요이다.
도 9는 일 구현예에 따른 단백질에 대한 동역학 데이터 및 모델 적합의 개요이다.
도 10은 실험 조건의 개략도이다.
도 11은 구현예에 따른 단백질에 대한 AMP 수준을 보여주는 그래프이다.
도 12는 구현예에 따른 단백질에 대한 생체 내 결과를 보여주는 그래프이다.
본 개시는 특히 가용화된 CD39의 특정 변형이 놀랍도록 활성인 단백질을 초래하며, 이는 여전히 안전하고 제조가 용이하다는 예상치 못한 발견을 기초로 한다.
아래의 구체적인 구현예에서 나타나는 바와 같이, 바람직한 구현예는 N 말단 결실, C 말단 결실 및 중심 결실로 구성된 목록으로부터 선택된 적어도 2가지의 변형을 갖는 가용화된 인간 아피라제, 예컨대 서열번호 4, 서열번호 6, 서열번호 32, 서열번호 54, 서열번호 56, 서열번호 70, 서열번호 76, 및 서열번호 78로 구성된 군으로부터 선택된 서열을 포함하는 가용화된 인간 아피라제이다.
본 발명자들은 면역원성 증가의 위험과 이에 따른 안전성 위험의 증가 때문에 여전히 너무 많은 변형을 도입하지 않으면서 활성과 발현 능력 둘 다를 보유하는 가용화된 인간 아피라제를 달성하기 위해 여러 가지 상이한 서열 변형 전략을 시도하였다. 놀랍게도, 효율과 인간 아피라제 발현 능력 둘 다를 증가시키는 동시에 너무 많은 면역원성 위험을 부가하지 않는 것으로 밝혀진 하나의 서열 변형은 중심 부분의 결실, 소위 델타 MIL(ΔMIL) 변형이었다.
본 발명의 구현예에 따른 가용화된 인간 아피라제의 발현을 증가시키기 위하여, N 말단 발현 태그를 시험하였다. 다양한 N 말단 발현 태그가 당해 분야에 공지되어 있지만, 놀랍게도 모든 태그가 효과가 있지는 않았다. 본 발명자들은 몇몇 태그가 효과가 있음을 발견했지만, 예상할 수는 없었다.
이러한 N 말단 태그는 서열번호 131, 서열번호 133, 서열번호 135, 서열번호 137, 서열번호 139 또는 서열번호 141이었다. 본원에 제시된 바와 같이, 특히 바람직한 태그는 서열번호 133, 서열번호 135 또는 서열번호 137이다.
구체적인 세부 사항은 아래 실시예 9 내지 13에 기재되어 있다. 그러나 이러한 실시예의 예측 불가능한 속성을 설명하기 위해, 비교 요약을 표 1에 제시하였다.
[표 1]
바람직한 구현예의 요약.
1.
정의
당업자가 본 발명을 실시하는 것을 용이하게 하기 위해, 다음 용어를 본 설명 전반에 걸쳐 사용한다.
용어 "CD39" 및 "hCD39"는 본 개시 전체에 걸쳐 동의어로 사용되며, 달리 언급되지 않는 한, UniProt P49961 또는 서열번호 1에 따른 인간 분화 클러스터 39(CD39)를 의미한다.
용어 "아피라제"는 달리 언급되지 않는 한 인간 아피라제를 지칭한다. 본원에서 사용되는 "가용화된 아피라제"는 야생형 단백질로서 세포막에 결합되어 존재하는 아피라제가 변형되어 더 이상 세포막에 결합되어 있지 않고, 가용성 상태로 존재함, 즉, 더 이상 세포막에 고정되어 있지 않음을 의미한다.
약어 "MIL"은 세포막을 관통하여 물리적으로 고정된 N 말단 및 C 말단 부분 이외에, 세포막과 상호작용하는 야생형 (인간) CD39 단백질의 중심 부분인 막 상호작용 루프(membrane interaction loop)를 지칭한다. 용어 "델타 MIL", 또는 "ΔMIL"은 야생형 (인간) CD39로부터의 MIL 서열의 결실을 지칭한다.
수치 x와 관련된 용어 "약"은, 예를 들어 +/-10%를 의미한다. 수치 범위 또는 숫자 목록의 앞에 사용될 때, "약"이라는 용어는 시리즈의 각각의 숫자에 적용되고, 예를 들어 "약 1~5"라는 어구는 "약 1 내지 약 5"로 해석되어야 하거나, 예를 들어 "약 1, 2, 3, 4"라는 어구는 "약 1, 약 2, 약 3, 약 4"로 해석되어야 한다.
"실질적으로"라는 단어는 "완전히"를 배제하지는 않고, 예를 들어 Y가 "실질적으로 없는" 조성물은 Y가 완전히 없을 수 있다. 필요한 경우, "실질적으로"라는 단어는 본 개시의 정의로부터 생략될 수 있다.
"포함하는"이라는 용어는 "구성된"을 또한 포괄하고, 예를 들어 X를 "포함하는" 조성물은 X만으로 구성될 수 있거나, 추가의 어떤 것, 예를 들어 X + Y를 포함할 수 있다.
천연 폴리펩티드 및 이의 기능적 유도체와 관련하여 "동일성"은, 서열 동일성의 일부로서 임의의 보존적 치환을 고려하지 않으면서, 최대 동일성 백분율을 달성하도록 서열을 정렬하고 필요한 경우 갭을 도입한 후 상응하는 천연 폴리펩티드의 잔기와 동일한 후보 서열에서의 아미노산 잔기의 백분율로서 본원에서 정의된다. N 말단 또는 C 말단 연장이나 삽입 어느 것도 동일성을 감소시키는 것으로 해석되어서는 안 된다. 정렬을 위한 방법 및 컴퓨터 프로그램은 잘 알려져 있다. 동일성 백분율은 일반적인 정렬 알고리즘, 예를 들어, 문헌[Altshul et al. ((1990) J. Mol. Biol., 215: 403 410)]에 기술된 BLAST(Basic Local Alignment Search Tool); 문헌[Needleman et al. ((1970) J. Mol. Biol., 48: 444 453)]의 알고리즘; 또는 문헌[Meyers et al. ((1988) Comput. Appl. Biosci., 4: 11 17)]의 알고리즘에 의해 결정될 수 있다. 일련의 매개변수는 갭 페널티 12, 갭 연장 페널티 4, 및 프레임쉬프트 갭 페널티 5를 갖는 블로섬(Blosum) 62 스코어링 매트릭스일 수 있다. 2개의 아미노산 또는 뉴클레오티드 서열 사이의 동일성 백분율은 또한 PAM120 가중 잔기 표, 갭 길이 페널티 12 및 갭 페널티 4를 사용하는, ALIGN 프로그램(버전 2.0)에 통합된 문헌[E. Meyers and W. Miller ((1989) CABIOS, 4:11-17)]의 알고리즘을 사용하여 결정될 수 있다.
"아미노산(들)"은 예를 들어 모든 천연 발생 L-α-아미노산을 지칭하고, D-아미노산을 포함한다. 어구 "아미노산 서열 변이체"는 본 개시에 따른 서열과 비교하여 아미노산 서열에 일부 차이가 있는 분자를 지칭한다. 예를 들어, 명시된 서열의, 본 개시에 따른 단백질의 아미노산 서열 변이체는 여전히 아피라제 활성을 갖는다. 아미노산 서열 변이체는 치환 변이체(본 개시에 따른 폴리펩티드에서 동일한 위치에 적어도 하나의 아미노산 잔기가 제거되고 그 위치에 상이한 아미노산이 삽입된 것), 삽입 변이체(본 개시에 따른 폴리펩티드의 특정 위치의 아미노산에 바로 인접하여 삽입된 하나 이상의 아미노산을 갖는 것) 및 결실 변이체(본 개시에 따른 폴리펩티드에서 하나 이상의 아미노산이 제거된 것)를 포함한다.
용어 "치료"는 본원에서 대상체에 대한 본 발명에 따른 아피라제의 적용 또는 투여, 또는 대상체 또는 대상체로부터의 단리된 조직 또는 세포주에 대한 상기 아피라제를 포함하는 제약 조성물의 적용 또는 투여로서 정의되며, 여기서 대상체는 조직 손상, 조직 손상과 관련된 증상을 가지며, 목적은 특히 세포 외 ATP의 수준을 감소시켜 조직 손상 또는 조직 손상의 임의의 관련 증상을 완화, 경감, 또는 개선하는 것이다.
또한, "치료"는 대상체에 대한 아피라제를 포함하는 제약 조성물의 적용 또는 투여, 또는 대상체로부터의 단리된 조직 또는 세포주에 대한 본 발명의 아피라제를 포함하는 제약 조성물의 적용 또는 투여를 의미하며, 여기서 대상체는 조직 손상 또는 조직 손상과 관련된 증상을 가지며, 목적은 조직 손상 또는 조직 손상의 임의의 관련 증상을 경감, 완화, 또는 개선하는 것이다.
용어 "예방"은 예방적 또는 방지적 처치를 의미하며, 이는 질환, 장애, 및/또는 이와 관련된 증상의 발병을 지연시키는 것 또는 예방하는 것과 관련된다.
본원에서 사용되는 바와 같이, 대상체가 생물학적으로, 의학적으로 또는 삶의 질에 있어서 이러한 치료에서 이익을 얻는 경우 이러한 대상체는 이러한 치료를 "필요로 한다".
"제약상 허용 가능한"이라는 용어는 활성 성분(들)의 생물학적 활성의 효과를 방해하지 않는 비독성 물질을 의미한다.
본원에서 사용되는 바와 같이, 대상 화합물의 "투여"라는 용어는 치료를 필요로 하는 대상체에게 본 발명의 화합물 및 이의 전구약물을 제공하는 것을 의미한다. 1종 이상의 추가 치료제와 "병용한" 투여는 임의의 순서 및 임의의 투여 경로로의 동시(병행) 및 연속 투여를 포함한다.
본원에서 사용되는 바와 같이, "치료 유효 용량"은 환자(예컨대, 인간)에게 단일 또는 다중 용량 투여 시 장애 또는 재발성 장애를 치료하거나, 예방하거나, 그의 발병을 예방하거나, 치유하거나, 지연시키거나, 그의 중증도를 감소시키거나, 그의 적어도 하나의 증상을 완화하기에, 또는 그러한 치료의 부재 하에서 예상되는 것 이상으로 환자의 생존을 연장하기에 유효한 아피라제의 용량(양)을 지칭한다. 단독으로 투여된 개별 활성 성분(예를 들어, 아피라제)에 적용되는 경우, 이 용어는 그 성분을 단독으로 지칭한다. 조합에 적용되는 경우, 이 용어는, 조합하여, 연속적으로, 또는 동시에 투여되든지 간에, 치료 효과를 가져오는 활성 성분들을 합한 용량 또는 양을 지칭한다.
어구 "투여 요법"은 병을 치료하는 데 사용되는 요법, 예를 들어, 조직 손상의 치료 중에 사용되는 투약 프로토콜을 의미한다.
어구 "투여하기 위한 수단"은 환자에게 약물을 전신 투여하기 위해 이용 가능한 임의의 도구(사전 충전된 시린지, 바이알 및 시린지, 주사 펜, 자동주사기, 정맥 내(i.v.) 드립 및 백, 펌프, 패치 펌프 등을 포함하나 이에 한정되지 않음)를 나타내기 위해 사용된다. 이러한 물품을 이용해, 환자가 약물을 자가 투여(즉, 스스로 약물을 투여)할 수 있거나, 의사가 약물을 투여할 수 있다.
2.
실시예 1: 무막 CD39
야생형 인간 아피라제 CD39(hCD39, UniProt P49961, 또는 서열번호 1)는 N 말단의 막관통 도메인(추정 아미노산 17~37), 중심 추정 막 상호작용 루프(MIL 추정 아미노산 193~204) 및 C 말단 막관통 도메인(추정 아미노산 479~499)에 의해 세포막에 자연스럽게 고정된다. 포유동물 숙주세포를 이용한 CD39의 가용성 변이체의 발현을 가능하게 하기 위하여, CD39 서열의 몇몇 요소를 변형하여 무막, 또는 가용화된, 단백질을 수득하였다. 천연 리더 서열 및 N 말단 막관통 영역을 분비 리더 및 정제 태그로 치환하였다(서열번호 133). CD39의 세포 외 도메인의 경계를 변경하여 발현, 정제 및 활성 파라미터를 최적화하였다(각각 서열번호 1의 아미노산 번호 38~476, 서열번호 1의 아미노산 번호 39~469, 서열번호 1의 아미노산 46~461, 및 서열번호 1의 아미노산 46~476). 시스테인을 알라닌으로 치환하거나 이황화 가교(서열번호 107, 109, 111, 113, 및 115)로 구성된 루프를 단축하여, 응집 경향 및 효소 활성에 미치는 시스테인 및 이황화 가교의 영향을 체계적으로 평가하였다. 소수성 아미노산의 스트레치는 랫트-CD39의 구조 연구에서 기술되었고(문헌[Zebisch et al, J.Mol. Biol. (2012), 415, 288-306, 야생형 랫트 CD39, Uniprot P97687, 서열번호 2에 기재됨), 이 루프는 세포막과 상호작용할 수 있다고 생각된다(MIL). 본 발명자들은 이러한 결과를 서열 정렬에 의해 인간 CD39 서열로 바꾸어 루프 결실이 있는 CD39 변이체(서열번호 4에 기재된 바와 같은, CD39ΔMIL 또는 EP28)를 생성하였다. 기능적 CD39의 발현 수준 및 열 안정성에 미치는 MIL의 결실(또는 델타/Δ)의 영향을 평가하였다.
서열번호 1과 서열번호 4의 서열 정렬을 보여주는 도 1에서 볼 수 있듯이, N 말단 아미노산 1 내지 27, C 말단 아미노산 477 내지 510, 및 중심 막 상호작용 루프(MIL) 아미노산 193 내지 204를 wtCD39(서열번호 1)로부터 결실시켜 CD39ΔMIL(서열번호 4)을 생성하였다.
열 안정성에 미치는 상이한 서열 변형의 영향을 연구하였다. 또한, CHO 세포 발현 수율 및 단량체 함량에 미치는 상이한 서열 변형의 영향을 연구하였다.
(1)
방법
(a)
발현 플라스미드의 생성
호모 사피엔스에 대한 코돈 최적화를 포함한, 상이한 hCD39 경계 변이체 및 막 상호작용 루프(MIL) 결실을 암호화하는 DNA 서열을 GeneArt(Life Technologies Inc., 독일 레겐스부르크 소재)에서 주문하였다. hCD39 변이체를 암호화하는 서열을 GeneArt 유래의 벡터 또는 이의 내부 생성 변이체로부터 표준 분자생물학 기법에 의해 포유동물 세포에서의 분비에 적합한 발현 벡터로 서브클로닝하였다. 시스테인 가교 결실 변이체에 존재하는 시스테인에서 알라닌으로의 돌연변이를 변형된 올리고뉴클레오티드에 의해 표적화하였고, 후속 어셈블리 PCR 단계 후, 생성된 단편을 이전에 언급된 동일한 발현 벡터로 서브클로닝하였다. 발현 벡터의 요소는 프로모터(거대세포 바이러스(CMV) 인핸서-프로모터), 분비를 용이하게 하기 위한 신호 서열, 폴리아데닐화 신호 및 전사 종결인자(소 성장 호르몬(BGH) 유전자), 에피솜 복제 및 원핵생물에서의 복제를 가능하게 하는 요소(예를 들어 SV40 원점 및 ColE1 또는 당해 분야에 공지되어 있는 다른 것) 및 선택을 가능하게 하기 위한 요소(암피실린 저항성 유전자 및/또는 제오신 마커)를 포함한다. 절단된, 가용화된 인간 CD39 버전의 목록을 표 2에 예시하였다. 아미노산 변형은 서열번호 1과 관련하여 넘버링하였다.
[표 2]
절단된, 가용화된 인간 CD39 버전.
(b)
hCD39 변이체의 마이크로 규모의 발현
혈청 부재 하에 단백질의 일시적인 발현을 위한 바람직한 숙주세포주의 하나로서 (본원에 참조로 포함된 제WO2006096989A2호에 개시된 바와 같은) 293-6E 세포를 마이크로 규모 실험을 위해 선택하였다. 형질감염 시약으로서 FuGene HD(Roche Applied Science, 카탈로그 번호 04709705001)를 사용하여 형질감염을 수행하였다. 세포의 형질감염 및 증식을 위해 V3 무혈청 배양 배지(Bioconcept, 카탈로그 번호 V3-K)를 이용하여 현탁 배양액에 293-6E 세포를 배양하였다. 5% CO2의 가습 인큐베이터 내의 오비탈 쉐이커(100~120 rpm) 상의 Corning 쉐이크 플라스크(Corning, 미국 매사추세츠 주 턱스베리 소재)(시드 플라스크)에서 세포를 성장시켰다. 시드 배양물의 세포는 지수 성장기(세포 밀도 5x105 ~ 3x106개/mL)에서 유지되어야 하며 형질감염의 경우 90% 초과의 생존율을 보여야 한다. 이 범위를 벗어난 세포 밀도는 희석 후 지연 단계로 이어지거나 형질감염 효율의 감소를 초래할 것이다.
마이크로 규모(0.5 ml)의 형질감염의 경우, 시드 배양물로부터 세포 분액을 취하여 V3 무혈청 배양 배지 중에 0.5x106개 세포/mL로 조정하였다. DNA 용액(용액 1이라 함)을 14 μl의 V3 무혈청 배양 배지에 0.5 μg의 hCD39 발현 플라스미드를 희석하여 준비한 다음, 2.3 μl의 FuGene HD 용액도 14 μl의 V3 무혈청 배양 배지에 희석하였다(용액 2). 두 용액 모두를 실온(RT)에서 5~10분 동안 배양하였다. 그 후, 용액 2를 부드럽게 혼합하면서 용액 1에 첨가하고 실온에서 추가로 5~15분 동안 배양하였다. 그 후, 형질감염 혼합물을 48-웰 조직 배양 플레이트(Corning, 미국 매사추세츠 주 턱스베리 소재)에 0.5x106개/mL로 시딩한 세포 0.5 ml에 첨가하고, 플레이트를 5% CO2의 가습 인큐베이터 내의 오비탈 쉐이커(300 rpm) 상에 위치시켰다. 4℃에서 10분 동안 4000 rpm에서 원심분리(Heraeus, Multifuge 3 S-R, Thermo Scientific, 미국 일리노이 주 락포드 소재)하여 형질감염 3일 후 배양물을 수확하였다. 회수된 세포 상청액을 추가 처리할 때까지 4℃에 보관하였다.
(c)
마이크로 규모의 발현 상청액에 대한 웨스턴 블롯 분석
재조합 hCD39 변이체의 발현 및 정확한 형성을 확인하기 위해 마이크로 규모의 발현 상청액에 대해 웨스턴 블롯 분석을 수행하였다. 8 μl의 상청액을 E-PAGE™ 로딩 버퍼(4x, Invitrogen, #EPBNF-01)에 희석하고 비 환원 조건에서 E-Page 48, 8% 겔(Invitrogen, #EP04808)에 로딩하였다. 겔을 23분 동안 E-base 마더 장치(Invitrogen)에서 러닝시키고, 단백질을 제조사의 지침(7분 실행)에 따라 iBlot 시스템(Invitrogen)을 사용하여 니트로셀룰로스 막(Invitrogen IB301001)으로 옮겼다. TBS/0.05 Tween20(TBST)에서 3회 세척한 후, 막을 5% 밀크/TBST와 함께 부드럽게 교반하면서 1시간 동안 배양한 다음, 2% 밀크/TBST에 희석한, 4 μg/ml의 항-APP 마우스 항체 용액(단백질 태깅에 사용되는 아밀로이드 전구체 단백질(APP)의 펩티드 스트레치에 대해 Novartis 내부에서 얻은 항체)과 함께 1시간 동안 배양하였다. 추가의 3회 세척 단계 후, 막을 2% 밀크/TBST에 희석한 항-마우스 IgG-알칼리 포스파타제(Sigma-Aldrich, A5153-1ML)의 1:1000 희석액과 함께 배양하고, TBST에서 다시 3회 세척한 다음, TBS에서 헹굼 단계를 수행하였다. 제조사의 지침에 따라 SIGMAFAST™ BCIP®/NBT(Sigma-Aldrich, #B5655-25TAB)를 사용하여 1~5분 동안 신호를 발생시키고, 막을 물로 헹구어 중지시켰다.
(d)
고체상 AxP 분해효소 분석
ATP 분해효소, ADP 분해효소 및 AMP 분해효소 활성을 마이크로 규모 발현 상청액으로부터 플레이트 상에 포획된 hCD39 변이체 상에서 Pi ColorLock Gold 인산염 검출 시스템(Innova Biosciences, 카탈로그 번호 303-0030)을 이용하여 결정하였다(고체상 AxP 분해효소 분석). 이 방법은 제조업체가 권장한 용액 기반 분석(액체상 Axp 분해효소 분석법)과 비교하여 덜 민감한 것으로 밝혀졌으나, 마이크로 규모의 발현 상청액에 잠재적으로 존재하는 숙주세포 효소에 의해 매개되는 AxP 분해효소를 감소시키는 장점이 있다. PBS에 희석된, 20 μl의 항-APP 마우스 항체 10 μg/ml의 용액 항체(단백질 태깅에 사용되는 아밀로이드 전구체 단백질(APP)의 펩티드 스트레치에 대해 Novartis 내부에서 얻은 항체)를 maxisorp 384 웰 투명 플레이트(Nunc)의 각 웰에 첨가하고 4℃에서 밤새 배양하였다. TBST로 3회 세척한 후, 웰을 실온에서 100 μl의 5%의 밀크/TBST를 이용하여 부드럽게 교반하면서 1시간 동안 차단하였다. 추가 3회의 세척 단계 후, 2%의 밀크/TBST 중 20 μl의 연속 희석된 마이크로 규모의 발현 상청액을 웰에 3 반복하여 첨가하고, 부드럽게 교반하면서 실온에서 2시간 동안 배양하였다. 그 후, 웰을 100 μl의 TBST로 다시 4회, 80 μl의 50 mM Tris-Cl/5 mM MgCl2 pH 7.5로 2회 세척하였다. 50 mM의 Tris-Cl/5 mM의 MgCl2 pH 7.5에 희석된 80 μM의 아데노신 인산염 용액 30 μl(ATP: SIGMA A2383, ADP: SIGMA A2754)를 각각 3 반복하여 첨가하고, 37℃에서 24시간 동안 배양하였다. 제조사의 지침에 따라 10분 동안 준비된 7.5 μl의 Gold 시약 믹스를 사용하여 신호를 발생시켰고, 3 μl의 안정화제를 사용하여 반응을 중지시켰다. TECAN Genios Pro 기기를 사용하여 620 nm에서의 흡광도를 판독하였다.
(2)
결과
(a)
hCD39 발현 수준에 미치는 경계, 막 상호작용 루프(MIL) 결실 및 시스테인 가교 결실의 효과
상이한 hCD39 변이체의 발현 수준을 평가하기 위해, 상응하는 발현 플라스미드를 0.5 ml의 293-6E 세포에서 2 반복하여 형질감염시키고, 형질감염 3일 후 수집된 상청액에 대해 웨스턴 블롯(항-APP 검출 Ab)을 수행하였다. 결과를 도 2a 및 도 2b에 도시하였다.
결과는 aa46에 비해 aa38에서 시작하는 hCD39의 더 높은 발현 수준을 나타낸다. N 말단 경계와 MIL 결실은 발현 수준에 주된 영향을 미치지 않는 것으로 보인다. hCD39(aa46-461)의 맥락에서 첫 번째 또는 네 번째의 시스테인 가교가 결실된 hCD39의 더 높은 발현 수준 또한 관찰되었다. 또한, hCD39(aa46-461) ΔMIL 백본을 사용하여, 첫 번째 시스테인 가교 결실의 더 높은 발현 수준이 확인되었다.
(b)
hCD39 활성에 미치는 경계, 막 상호작용 루프(MIL) 결실 및 시스테인 가교 결실의 효과
CD39 효소 활성을 위에 기술된 상청액 샘플에 대한 고체상 AxP 분해효소 분석에 의해 측정하였다. 결과를 표 3, 도 3 및 도 4에 제시하였다.
[표 3]
CD39 변이체에 대한 고체상 ATP 분석
MIL의 결실은 기능적으로 발현된 CD39 재조합 단백질의 비율을 증가시키는 것으로 보인다. 상이한 경계는 활성인 hCD39 활성에 주요한 영향을 나타내지 않는다. 결과는 모든 시스테인 가교 결실 변이체의 강하게 감소되었거나 완전하게 파괴된 ATP 분해효소 활성을 나타낸다. 유사한 결과가 고체상 ADP 분해효소 분석을 이용하여 얻어졌다. 따라서, 놀랍게도, 효율성 및 CD39를 발현하는 능력 둘 다를 증가시키는 서열 변형은 델타 MIL(ΔMIL) 변형이다.
3.
실시예 2: 발현 태그
후보의 발현 특성을 개선하기 위하여, 상이한 발현 태그를 시험하였다.
IL-2의 N 말단 부분(서열번호 131)에 기초한 상이한 발현 태그를 표 4에 기재된 바와 같이 시험하였다. 서열번호 131에 따른 발현 태그 1-16 아미노산(aa)을 Geneart에 의해 합성하였다.
[표 4]
IL-2 발현 태그 변이체 개요
서열번호 4에 기재된 바와 같이 CD39ΔMIL과 관련하여 모든 발현 태그를 시험하였다. 모든 구성체는 APP 태그와 His 태그를 포함하였다.
도 5에 제시된 바와 같이 벡터 pRS5a를 발현에 사용하였다. 프라이머 쌍은 표 4에 기재된 바와 같았다.
어닐링 온도는 모든 경우에 64℃였다.
1 μl의 주형 DNA 모액, 25 μl의 Kapa Hifi Hotstart 중합효소(kappa Biosystems/KK2602)를 혼합하여 PCR 용액을 제조하였다. 1.5 μl의 정방향 프라이머, 1.5 μl의 역방향 프라이머를 이용하였고, 물을 이용하여 최종 부피를 50 μl로 조정하였다.
표 5의 스케줄에 따라 PCR 반응을 수행하였다.
[표 5]
PCR 스케줄
PCR 반응이 완료된 후, 제조사의 지침에 따라 Wizard® SV 겔 및 PCR 클린-업 키트(Promega, No. 9282), 1개 컬럼, 30 μl의 용리를 이용하여 DNA 추출을 수행하였다.
CutSmart(R) 완충액 중 New England Biolabs(NEB)가 제공한 효소 NruI-HF(NEB # R3192) 및 NotI-HF(NEB # R3189)로 삽입물과 벡터를 절단하였다. 반응 시간은 37℃에서 3시간이었다.
생산자의 유효한 프로토콜에 따라 Rapid DNA 탈인산화 및 라이게이션 키트(Fa. Roche, No. 04898117001)를 이용하여 탈인산화된 벡터로 라이게이션을 밤새 수행하였다.
다음날, DNA-Miniprep 및 정방향 프라이머 P270(서열 번호 165) 및 역방향 프라이머 P271(서열 번호 166)을 이용한 서열 분석을 위해 단일 클로니를 선택하였다.
또한, 표 6에 따라 발현을 증가시키는 것으로 당해 분야에 공지된 몇몇 단백질 서열을 시험하였다.
[표 6]
선행기술 태그
시험한 생성 조합을 표 7에 기재하였다.
[표 7]
시험한 구성체
표 6의 선행기술 태그 중 어느 것도 단백질의 발현을 제공하지 않았다(데이터 미도시). 이는 예상하지 못했는데, 선행기술에 따르면 이들 서열은 발현을 증가시킨다고 교시하고 있기 때문이다.
4.
실시예 3: 추가 돌연변이
가용성 CD39의 특징을 개선하고 이를 제약 개발에 적합하게 만들기 위해, 서열번호 4에 기재된 CD39ΔMIL인 EP28에 추가 변형을 도입하였다. 상이한 돌연변이 및 돌연변이된 변이체가 표 8에 제시되어 있으며, 이들은 서열번호 1에 기재된 바와 같은 야생형 CD39의 아미노산 위치에 따라 넘버링하였다.
[표 8]
점 돌연변이
활성 부위의 2개의 돌연변이가 더 큰 활성을 초래한다(365 및 412).
5.
실시예 4: 글리코실화 부위 제거
위의 EP14 변이체에 기초하여, 서열번호 1에 기재된 야생형 CD39의 아미노산 위치에 따라 넘버링된, 표 9에 따른 점 돌연변이를 도입하여 글리코실화 부위의 영향을 확인하였다.
[표 9]
글리코실화 부위 돌연변이
(a)
재료 및 방법
발현 벡터 pRS5a(도 5)를 클로닝에 사용하였다. 표 10에 기재된 바와 같은 프라이머를 사용하였다.
[표 10]
프라이머 서열
QuikChange Lightning 부위 특이적 돌연변이 유발 키트(Agilent, No. 210519-5)를 제조사의 지침에 따라 PCR에 사용하였다.
다음날, DNA-Miniprep을 위해 단일 클로니를 선택하고, 정방향 프라이머 P270(서열 번호 165) 및 역방향 프라이머 P271(서열 번호 166)을 이용한 서열 분석을 수행하였다.
(돌연변이 유발로 인한) 벡터 백본의 정확성을 보장하기 위해 다음의 방법을 사용하여 서열 분석된 삽입물 단편을 pRS5a의 새로운 벡터 백본(도 5) 내로 클로닝하였다.
APP_HIS-태그, 모액 농축물 3.3 μg/μl를 함유하는 발현 태그 서열번호 135와 함께 서열번호 36의 벡터 백본을 사용하여 벡터를 제조하였다.
10 μg의 벡터-DNA, 0.4 μl의 HindIII(100 U/μl, NEB), 2 μl의 EcoRI(20U/μl, NEB), 5 μl의 Cutsmart 완충액 10x 농축물(NEB), H2O를 최종 부피 50 μl까지 혼합하여 벡터를 소화시켰다. 소화는 37℃에서 3시간 동안 수행되었다.
탈인산화는 알칼리 포스파타제(송아지 내장)(CIP, NEB, No. M0290L) 10U/μl로 수행되었다. 소화 직후, 3 μl의 CIP를 소화된 벡터에 첨가하고 30분 동안 37℃에서 배양하였다. 소화 및 탈인산화된 벡터를 분취용 0.8%의 TAE 아가로스 겔에 로딩하고, 약 6100 bp의 정확한 밴드 크기의 벡터를 잘라내었다. Wizard® SV 겔 및 PCR 클린-업 키트(Promega, No. 9282), 1개 컬럼, 100 ul의 용리로 정화를 수행하였다. OD 260 nm는 64 ng/μl의 농도를 보여주었다.
42.5 μl의 DNA(각 DNA에 대해 약 3 내지 5 ug), 5 μl의 Cutsmart 완충액, 10x 농축물, NEB no B7204S, 0.4 μl의 HindIII-HF, 100 U/μl, NEB no. R3104S, 2 μl의 EcoRI-HF, 20 U/μl, NEB no. R3103L을 혼합하고, H2O로 부피를 50 μl로 조정하여 돌연변이된 삽입물 단편의 소화를 수행하였다. PCR 기기에서 37℃에서 3시간 동안 소화를 수행하였다. 소화된 삽입물을 분취용 0.8%의 TAE 아가로스 겔에 로딩하고, 약 1400 bp의 정확한 밴드 크기의 벡터를 잘라내었다. Wizard® SV 겔 및 PCR 클린-업 키트(Promega, No. 9282), 1개 컬럼, 30 μl의 용리로 정화를 수행하였다. OD 260 nm는 1 내지 25 ng/μl의 농도를 보여주었다.
Rapid DNA 라이게이션 키트(No. K1423, Fa. Thermo Scientific)와 함께 (벡터:삽입물 비 약 1:10)을 이용하여 라이게이션을 수행하였다. 4 μl의 5x 라이게이션 완충액을 1 μl의 리가아제, 2 μl의 벡터 단편, HindIII/EcoRI 소화된 모액 농축물 64 ng/μl, 13 μl의 삽입물 단편, HindIII/EcoRI 소화된, 모액 농축물 1 내지 25 ng/μl와 혼합하였다. 라이게이션을 RT에서 10분 동안 수행하였다.
형질전환은 10 μl의 라이게이션을 80 μl의 화학적 적격 XL1Blue 세포(Novartis, FS/RL)와 함께 얼음에서 30분 동안 배양하여 수행하였다. Eppendorf 인큐베이터에서 42℃에서 45초 동안 열 충격을 가한 후, 얼음에서 2분 동안 배양하였다. 그 후, 1 ml의 2YT 배지를 첨가하고, Eppendorf 진탕기(800 rpm)에서 37℃에서 1.5시간 동안 배양하였다. 세포를 7000 rpm에서 3분 동안 원심분리하고, LB/Carb/Gluc에 콜로니 플레이팅을 하였다. 플레이팅 후, 37℃에서 밤새 배양하였다.
다음날, DNA-Miniprep을 위해 단일 클로니를 선택하고, 정방향 프라이머 P270(서열 번호 165) 및 역방향 프라이머 P271(서열 번호 166)을 이용한 서열 분석을 수행하였다.
7일의 발현, 200 ml의 규모에 따라 정확한 서열을 HEK293 세포 내로 형질감염시켰다.
다음 재료를 사용하였다:
SV40 대형 T 항원을 구성적으로 발현하는 인간 배아 신장 세포(HEK293-T), 예를 들어, ATCC11268
실온에서 H2O에 용해시켜 NaOH로 pH 7.05로 조정한 폴리에틸렌이민 "MAX" MW 40.000(PEI)(Polysciences, Cat. 24765)
M11V3 무혈청 배양 배지(Bioconcept, CH, Cat: V3-K)
DNA: 공급업체에서 권장하는 프로토콜에 따라 Qiagen DNA 키트인 Midiprep-키트(No. 12943)로 제조됨.
일시적 형질감염을 위한 모든 세포 배양 작업은 무혈청 M11V3 배지에서 성장하는 현탁액 적응 HEK293-T 세포를 사용하여 수행된다.
5% CO2의 가습 CO2-인큐베이터 내의 오비탈 쉐이커(115 rpm) 상의 Corning 쉐이크 플라스크(Corning, 미국)(시드 플라스크)에서 세포를 성장시킨다.
사용된 세포는 지수성장기(세포 밀도 5x105 ~ 3x106개/ml)에 있었고, 생존율이 90%를 초과하였다.
계수된 세포를 사용하여 소규모(여기서는 20/50 또는 100 ml)로 형질감염을 수행하였고, 상응하는 세포의 양을 M11V3 배지를 사용하여 1.4x106개 세포/ml로 조정하였다. 최종 형질감염 부피의 36%의 세포 현탁액이 사용된다.
7%의 최종 부피의 M11V3에 1 mg/L의 최종 부피 DNA를 희석하고 부드럽게 혼합하여 DNA 용액(용액 1)을 제조한다. 멸균 여과되지 않은 DNA로 인한 배양물 오염을 방지하기 위해 Penc./Strep을 급이 후 형질감염에 추가했다. 그 후, 3 mg/L의 최종 부피의 PEI 용액을 7%의 최종 부피의 M11V3 중에 희석하고 부드럽게 혼합한다(용액 2). 두 용액 모두를 실온(RT)에서 5~10분 동안 배양한다. 그 후 용액 2를 용액 1에 부드럽게 혼합하면서 첨가하고, 실온에서 5~15분 더 배양한다. 배양 후, 형질감염 믹스를 세포에 첨가하고, 배양물을 4시간 동안 배양한다(115 rpm, 37℃, 5% CO2).
발현 7일 후에 상청액을 수확하였다.
원심분리 4500 rpm., 15분, 4℃(Heraeus, Multifuge 3 S-R)
멸균 필터를 통한 정화, 0.22 μm(Stericup 필터, Thermo Scientific, Cat.567-0020)
상청액을 추가 단계를 위한 정제로 전달한다. 1 ml의 상청액 샘플이 개방 접근 APP-컬럼의 IPC에 사용된다.
샘플 바이알은 유리 크림프 바이알, 2 ml Agilent, 카탈로그 번호 5182-0543 및 캡: 크림프 11 mm, 카탈로그 번호 5040-4667이었다.
5 ml의 Histrap HP 컬럼(GE Life Sciences, 주문번호 17-5248-02)을 이용하여 다음의 프로토콜에 따라 Aekta Pure 또는 Aekta Avant(GE Healthcare)에서 고정화 금속 친화성 크로마토그래피(IMAC)를 이용하여 단백질을 정제하였다. 사양을 표 11에 기재하였다.
[표 11]
IMAC 프로토콜
사용된 완충액은 표 12 및 표 13에 따라 구성되었다.
[표 12]
IMAC A, 평형화 및 세척 완충액
[표 13]
IMAC B, 용리 완충액
표 14에 따른, 생성된 단백질을 저장하였다.
[표 14]
구성체
(b)
결과 및 해석
수율 및 분석 SEC의 단량체 피크와 관련하여 돌연변이체의 개선이 없었다. 서열번호 137에 따른 발현 태그가 있는 모체 단백질(EP14)이 최선의 수율 및 분석에서 가장 높은 단량체 피크를 제공하였다. 최저 수율 및 최악의 단량체 피크는 돌연변이 N371Q로 달성되었다.
6.
실시예 5: 조합
성질을 더욱 개선하기 위하여, 위의 실시예 3에서 도입된 일부 돌연변이를 아래 표 15에 따라 조합하였다. 돌연변이는 서열번호 1에 기재된 바와 같은 야생형 CD39의 아미노산 위치에 따라 넘버링하였다.
[표 15]
구성체의 조합
(a)
재료 및 방법
표 16에 따른 프라이머를 사용하였다.
[표 16]
프라이머
다음의 피펫팅 계획을 이용하여 PCR 반응을 준비하였다:
5 μl의 10x 반응 완충액,
1 μl의 ds-DNA-주형(모액 농축물 100 ng/μl),
1.5 μl의 프라이머 1,
1.5 μl의 프라이머 2,
1 μl의 dNTP 믹스
1.5 μl의 QuickSolution 시약,
35.5 μl의 H2O(최종 부피 50 μl를 위함), 및
1 μl의 QuickChange Lightning Enzyme.
표 17에 따른 PCR 사이클링 파라미터를 사용하였다.
[표 17]
PCR 사이클링 파라미터
반응 직후, 2 μl의 DpnI 효소를 각 반응물에 첨가하고, 혼합하고, 37℃에서 5분 동안 배양하였다.
XL10-골드 초 적격 세포로의 형질전환을 다음과 같이 수행하였다. 세포를 얼음 위에서 해동시켰다. 45 μl/형질전환을 사용하였고, 2 μl의 B-ME를 각 바이알에 첨가하였다. 그 후, 3 μl의 DpnI 소화된 PCR 생성물을 첨가하고, 15 ml BD 튜브에서 얼음 위에서 30분 동안 배양하였다. 그 후, 샘플에 40초 동안 열 충격을 가하고, 2분 동안 얼음 위에서 배양하였다. 다음으로, 950 μl의 SOC 배지를 첨가한 후, 진탕 배양기에서 37℃에서 1.5시간 동안 배양하였다. 마지막으로, 세포를 LB-carb-플레이트에 플레이팅하고, 37℃에서 밤새 배양하였다. 다음날, DNA-miniprep 및 서열 분석을 위해 단일 콜로니를 선택하였다.
실시예 4에 기술된 바와 같이, 정확한 서열을 HEK293 세포 내로 형질감염시켰다.
다음에 따라 고정화 금속 친화성 크로마토그래피(IMAC)를 이용하여 단백질을 정제하였다. 95 ml의 상청액을 사용하였다(전체 중 약 4 ml을 분석(IPC)을 위해 보관한다).
사용한 재료:
니켈-NTA 아가로스, Qiagen, 카탈로그 번호/ID: 30230, Poly-Prep 크로마토그래피 컬럼, 비어 있음, BioRad, No. 731-1550, IMAC A 완충액 pH7.4(20 mM의 NaPO4-완충액 및 50 mM의 이미다졸 함유). IMAC B 완충액 pH7.4(20 mM의 NaPO4-완충액 및 300 mM의 이미다졸 함유). TBS(MilliQ-Water로 1x 농축물까지 희석된 10x-농축물). Ultracel-10 막을 구비한 Amicon Ultra-4 원심분리 필터 유닛, 10K, UFC801096.
공정 단계:
1. Qiagen의 니켈-NTA-아가로스 1 ml(= 0.5 ml CV)로 컬럼을 준비하였다;
2. 10 CV IMAC A로의 평형화;
3. 컬럼 상에 15/45 ml의 SN을 로딩함(플로우 스루 수집);
4. 10 CV IMAC A로 세척(15 ml의 Falcon 튜브에 수집);
5. 6.5 CV의 IMAC B에서 용리;
6. 용리액의 농도 결정;
7. Amicon Ultra-4 원심분리 필터 유닛 10K로 3.5 ml의 샘플을 약 400 μl까지 농축;
8. TBS를 첨가하여 완충액 교환 및 원심분리 5000;
40 μl의 각 샘플을 이용한 분석적 SEC를 이용하고 12 μl의 각 샘플을 이용한 단백질 겔을 이용하여 샘플을 분석하였다.
생성된 단백질을 저장하였다.
(b)
결과 및 해석
결과를 표 18에 제시하였다.
[표 18]
결과 개요
프로테아제 부위:
마트립타제를 삽입했을 때 수율이 없거나 매우 낮았다. 퓨린 부위의 경우, 약 40%의 수율이 있었다(그러나 형질감염의 경우, DNA의 50%만이 사용되었는데, 퓨린 플라스미드와의 공동 형질감염이기 때문이었다).
IL2-절단:
aa1-3이 포함되는 모든 절단은 비슷한 결과를 제공하며, aa1-3만이 다른 것들과 비교하여 약간 더 낮을 수 있지만, 이는 샘플간의 차이일 수 있다. 절단 aa4-12는 단백질 발현을 초래하지 않는다. 다른 모든 EP 변이체와 마찬가지로, IL2-출발점 및 hCD39-단백질 사이의 TSS 링커를 함유하는 EP28 사이에서 차이가 발견되지 않았다.
조합:
EP19(L424Q)와의 조합은 단백질 발현의 현저한 개선을 가져오지 않았다.
EP1(R113M)과의 조합은 분석적 SEC에서 더 낮은 응집을 나타내었다. NEG726은 잘 발현되었지만, 시험한 모든 것들 중에서 최악의 응집을 보였주었다(약 37%). EP14xEP17의 조합은 임의의 추가적인 개선을 가져오지 않았다(F365S + Y412F).
7.
실시예 6: 최종 후보의 클로닝
아래 표 19에 기재된 바와 같은 선택된 임상 후보를 추가 시험을 위해 발현시켰다.
[표 19]
최종 후보 개요
다음의 프라이머를 사용하였다:
[표 20]
프라이머
다음의 피펫팅 계획을 이용하여 PCR 반응을 준비하였다:
0.25 μl의 DMSO,
20 ng의 벡터
1.5 μl의 삽입물(45 ng/ μl),
2 μl의 5 x HF 완충액,
0.1 μl의 Phusion 중합효소,
0.08 μl의 dNTP 믹스
10-X μl의 ddH2O
표 17에 따른 PCR 사이클링 파라미터를 사용하였다.
[표 21]
PCR 사이클링 파라미터
반응 직후, 0.5 μl의 DpnI 효소를 각 반응물에 첨가하고, 혼합하고, 37℃에서 2시간 동안 배양하였다.
XL10-골드 초 적격 세포로의 형질전환을 다음과 같이 수행하였다. 세포를 얼음 위에서 해동시켰다. 45 μl/형질전환을 사용하였고, 2 μl의 B-ME를 각 바이알에 첨가하였다. 그 후, 3 μl의 DpnI 소화된 PCR 생성물을 첨가하고, 15 ml BD 튜브에서 얼음 위에서 30분 동안 배양하였다. 그 후, 샘플에 40초 동안 열 충격을 가하고, 2분 동안 얼음 위에서 배양하였다. 다음으로, 950 μl의 SOC 배지를 첨가한 후, 진탕 배양기에서 37℃에서 1.5시간 동안 배양하였다. 마지막으로, 세포를 LB-carb-플레이트에 플레이팅하고, 37℃에서 밤새 배양하였다. 다음날, DNA-miniprep 및 서열 분석을 위해 단일 콜로니를 선택하였다.
모든 구성체를 새로운 벡터 배경으로 서브클로닝하여 시퀀스가 정확함을 확인하였다. 이를 위하여, 모든 구성체를 PCR로 증폭시키고, G4S-링커를 삽입한 후, HindIII/EcoRI로 소화시켰다.
생성된 단백질을 저장하였다.
8.
실시예 7: 비교 단백질의 생성
(1)
삭제 돌연변이
생체 내 연구를 위한 음성 대조군 단백질을 생성하기 위하여, 1/2개의 돌연변이를 모 인간 CD39ΔMIL 단백질(EP28) 내로 삽입하였다. 이 돌연변이들은 이 단백질의 효소 활성을 제거하거나 낮추는 것으로 문헌에 기술되어 있다. 돌연변이 위치는 E174A 및 S218A이다.
다음의 프라이머를 사용하였다:
[표 22]
프라이머
다음의 피펫팅 계획을 이용하여 PCR 반응을 준비하였다:
5 μl의 10x 반응 완충액,
1 μl의 ds-DNA-주형(모액 농축물 100 ng/μl),
1.5 μl의 프라이머 1,
1.5 μl의 프라이머 2,
1 μl의 dNTP 믹스
1.5 μl의 QuickSolution 시약,
35.5 μl의 H2O(최종 부피 50 μl를 위함), 및
1 μl의 QuickChange Lightning Enzyme.
표 17에 따른 PCR 사이클링 파라미터를 사용하였다.
[표 23]
PCR 사이클링 파라미터
반응 직후, 2 μl의 DpnI 효소를 각 반응물에 첨가하고, 혼합하고, 37℃에서 5분 동안 배양하였다.
XL10-골드 초 적격 세포로의 형질전환을 다음과 같이 수행하였다. 세포를 얼음 위에서 해동시켰다. 45 μl/형질전환을 사용하였고, 2 μl의 B-ME를 각 바이알에 첨가하였다. 그 후, 3 μl의 DpnI 소화된 PCR 생성물을 첨가하고, 15 ml BD 튜브에서 얼음 위에서 30분 동안 배양하였다. 그 후, 샘플에 40초 동안 열 충격을 가하고, 2분 동안 얼음 위에서 배양하였다. 다음으로, 950 μl의 SOC 배지를 첨가한 후, 진탕 배양기에서 37℃에서 1.5시간 동안 배양하였다. 마지막으로, 세포를 LB-carb-플레이트에 플레이팅하고, 37℃에서 밤새 배양하였다. 다음날, DNA-miniprep 및 서열 분석을 위해 단일 콜로니를 선택하였다.
다음의 프로토콜에 따라 정확한 서열을 HEK293 세포 내로 형질감염시켰다.
10 μg의 벡터-DNA, 0.4 μl의 HindIII(100 U/μl, NEB), 2 μl의 EcoRI(20/μl, NEB), 5 μl의 Cutsmart 완충액 10x 농축물(NEB), H2O를 최종 부피 50 μl까지 사용하여 소화 완충액을 제조하였다. 소화 반응을 37℃에서 3시간 동안 수행하였다.
소화 직후, 탈인산화 반응을 수행하였다. 송아지 내장 알칼리 포스파타제(10 U/μl, CIP, NEB, No. M0290L)를 소화된 벡터 믹스에 첨가하고(3μl), 37℃에서 30분 동안 배양하였다.
소화 및 탈인산화된 벡터를 서브클로닝하여 서열을 확인하였다.
다음의 프로토콜에 따라 정확한 서열을 HEK293 세포 내로 형질감염시켰다.
다음의 재료를 이용하여 7일의 발현을 수행하였다; 1. SV40 대형 T 항원을 구성적으로 발현하는 인간 배아 신장 세포(HEK293-T, ATCC11268); 2. 폴리에틸렌이민 "MAX" MW 40.000(PEI)(Polysciences, Cat. 24765).
PEI 용액은 실온(RT)에서 900 ml의 세포 배양 등급의 물에 PEI 1 g을 조심스럽게 용해시켜 제조한다. 그 후, 최종 pH 7.05를 위해 NaOH로 중화시킨다. 마지막으로 부피를 1 L로 조정하고, 용액을 0.22 μm의 필터를 통해 여과하고, 분취액으로 분주하고, 추가 사용 시까지 -80℃에서 동결시킨다. 해동되면, 분취액을 -20℃에서 최대 3회까지 재냉동시킬 수 있지만, -20℃에서 장기간 보관해서는 안 된다.
M11V3 무혈청 배양 배지(Bioconcept, CH, Cat: V3-K).
일시적 형질감염을 위한 모든 세포 배양 작업은 무혈청 M11V3 배지에서 성장하는 현탁액 적응 HEK293-T 세포를 사용하여 수행된다.
소규모(< 5 L)의 형질감염을 위해, 5% CO2의 가습 CO2-인큐베이터 내의 오비탈 쉐이커(100 rpm) 상의 Corning 쉐이크 플라스크(Corning, 미국)(시드 플라스크)에서 세포를 성장시킨다.
일반적으로, 시드 배양물의 세포는 지수 성장기(세포 밀도 5x105 ~ 3x106개/mL)에 있어야 하며 90% 초과의 생존율을 나타내야 한다. 이 범위를 벗어난 세포 밀도는 분할 후 지연 단계로 이어지거나 형질감염 효능의 감소를 초래할 것이다.
소규모(여기서는 2 L)의 형질감염의 경우, 시드 배양물로부터 세포 분액을 취하여 M11V3 배지로 최종 부피의 36% 중 1.4x106개 세포/mL로 조정한다.
7%의 최종 부피의 M11V3에 1 mg/L의 최종 부피 DNA를 희석하고 부드럽게 혼합하여 DNA 용액(용액 1)을 제조한다. 배양물의 오염을 방지하기 위해, 이 용액을 0.22 μm의 필터(예를 들어, Millipore Stericup)를 이용하여 여과할 수 있다. 여기서는 작은 부피로 인해, 멸균 여과를 수행하지 않았다. 그 후, 3 mg/L의 최종 부피의 PEI 용액을 7%의 최종 부피의 M11V3 중에 희석하고 부드럽게 혼합한다(용액 2). 두 용액 모두를 실온(RT)에서 5~10분 동안 배양한다. 그 후, 용액 2를 부드럽게 혼합하며 용액 1에 첨가하고 실온에서 5~15분 더 배양한다(PEI가 DNA를 덮거나 양으로 하전된 입자로 응축시키며, 이는 음이온성 세포 표면 잔류물에 결합하여 엔도시토시스를 통해 세포 내로 들어오게 되므로, 배양 시간 동안 다시 혼합하지 않는다). 배양 후, 형질감염 믹스를 세포에 첨가하고, 배양물을 4시간 동안 배양한다(10 rpm, 37℃, 6% CO2).
마지막으로 다음 예에 따라 나머지 50%의 최종 부피의 M11V3 배지를 배양물에 공급한다: 접종 부피: 1.4x106개 세포/ml의 36 ml.
용액 1: 100 μg의 플라스미드 DNA가 있는 7 ml의 M11V3 배지. 용액 2: 300 μg의 PEI(300 μl)가 있는 7 ml의 M11V3 배지
공급: 50 ml의 M11V3, 총 100 ml.
다음에 따라 고정화 금속 친화성 크로마토그래피(IMAC)를 이용하여 단백질을 정제하였다. 95 ml의 상청액을 사용하였다(전체 중 약 4 ml을 분석(IPC)을 위해 보관한다).
사용한 재료:
니켈-NTA 아가로스, Qiagen, 카탈로그 번호/ID: 30230, Poly-Prep 크로마토그래피 컬럼, 비어 있음, BioRad, No. 731-1550, IMAC A 완충액 pH7.4(20 mM의 NaPO4-완충액 및 50 mM의 이미다졸 함유). IMAC B 완충액 pH7.4(20 mM의 NaPO4-완충액 및 300 mM의 이미다졸 함유). TBS(MilliQ-Water로 1x 농축물까지 희석된 10x-농축물). Ultracel-10 막을 구비한 Amicon Ultra-4 원심분리 필터 유닛, 10K, UFC801096.
공정 단계:
1. Qiagen의 니켈-NTA-아가로스 1 ml(= 0.5 ml CV)로 컬럼을 준비하였다;
2. 10 CV IMAC A로의 평형화;
3. 컬럼 상에 15/45 ml의 SN을 로딩함(플로우 스루 수집);
4. 10 CV IMAC A로 세척(15 ml의 Falcon 튜브에 수집);
5. 6.5 CV의 IMAC B에서 용리;
6. 용리액의 농도 결정;
7. Amicon Ultra-4 원심분리 필터 유닛 10K로 3.5 ml의 샘플을 약 400 μl까지 농축;
8. TBS를 첨가하여 완충액 교환 및 원심분리 5000;
40 μl의 각 샘플을 이용한 분석적 SEC를 이용하고 12 μl의 각 샘플을 이용한 단백질 겔을 이용하여 샘플을 분석하였다.
생성된 단백질을 저장하였다.
(2)
플러스MIL
중첩 연장 PCR을 이용하여 막 상호작용 루프(aa193-204)와 함께 EP14aa1-3의 클로닝을 수행하였다.
다음의 프라이머를 사용하였다:
[표 24]
프라이머
다음의 피펫팅 계획을 이용하여 PCR 반응을 준비하였다:
1.2 μl의 Phusion Hot Start 중합효소,
24 μl의 5x HF-완충액,
0.96 μl의 100 mM dNTP(25 mM의 각 dNTP),
0.6 μl의 정방향 프라이머,
0.6 μl의 역방향 프라이머,
92.64 μl의 DEPC H2O.
표 17에 따른 PCR 사이클링 파라미터를 사용하였다.
[표 25]
PCR 사이클링 파라미터
반응 직후, 2 μl의 DpnI 효소를 각 반응물에 첨가하고, 혼합하고, 37℃에서 2시간 동안 배양하였다.
2 μl의 PCR 생성물을 96-웰 PCR 플레이트로 옮기고, 얼음 위에서 냉각시켜 형질전환을 수행하였다. 20 μl의 STELLAR 화학 성분 박테리아를 첨가하고 위아래로 한 번 피펫팅하여 조심스럽게 혼합하였다. 샘플을 얼음 위에서 30분 동안 배양한 다음, PCR 기기에서 42℃에서 45초 동안 배양한 다음, 얼음 위에서 60초 더 배양하였다. 마지막으로, 90 μl의 SOC 배지를 첨가하고, 37℃에서 1시간 동안 배양하였다. 전체 형질감염 믹스를 LB-암피실린 또는 LB-카르베니실린 플레이트에 플레이팅하고 밤새 37℃에서 성장시켰다.
서열번호 155에 따른 아미노산 서열을 갖는, 생성된 단백질 EP14_플러스MIL을 보관하였다.
9.
실시예 8: 효소 활성
효소 활성 분석을 이용하여 이전의 실시예에서 생성된 후보의 특성을 규명하였다.
다음의 시약을 사용하였다: 파이(Pi) 불포함 완충액, 인산염 불포함 생리 식염수(140 mM NaCl, 5 mM KCl, 1 mM MgCl2, 2 mM CaCl2, 10 mM Hepes, pH7.4); 및 파이 불포함 완충액 + 2% BSA, 20 mg/ml BSA를 함유하는, 인산염 불포함 생리 식염수; (서열번호 1에 따른) CD39 단백질; ATP.
2 반복의 CD39 용액을 2 μg/ml으로 제조하였다. 15 μl ATP 모액 + 1185 μl 완충액, 총 1.2 ml로부터 2 반복의 ATP 용액을 1000 μM로 제조하였다.
최종 120 μl/웰로 채워진 48 웰 PCR 플레이트에 60 μl의 ATP를 60 μl의 CD39 또는 대조군의 경우 60 μl의 파이 불포함 완충액과 혼합하여 효소 반응을 연구하였다. 최종 농도는 500 μM의 ATP 및 1 μg/ml의 CD39였다.
샘플을 각각 0, 5, 15, 30, 60, 90, 및 150분 동안 37℃에서 배양하였다. 그 후, 샘플을 파이 방출 분석 또는 HPLC에 의해 평가하였다.
(1)
파이 방출 분석
(a)
재료 및 방법
제조사의 지침에 따라 표준 파이 검출 키트로부터 시약을 제조하였다.
물에 희석하여 파이를 이용한 표준 곡선을 준비하였다. 파이 모액(100 μM)의 1:2 연속 희석물을 제조하였다: 450 μl + 450 μl의 물. 표준 곡선 농도는 다음과 같았다: 50 μM / 25 μM / 12.5 μM / 6.25 μM / 3.1 μM / 1.5 μM / 0 μM.
Gold 시약 믹스를 다음과 같이 제조하였다: 4 ml의 골드 시약 + 40 μl의 촉진제(3개 플레이트의 경우). 96 웰 플레이트에서, 샘플을 H2O에 1:10으로 희석하였다(물에서의 희석: 10 μl의 샘플 + 90 μl의 H2O). 50 μl의 1:10 희석 샘플을 96 절반 면적 웰 플레이트(Corning, 3690)의 각 웰에 분주하였다. 12.5 μl의 Gold 시약 믹스를 각 웰에 첨가하고(25%의 샘플 부피), 샘플을 실온에서 10분 동안 배양하였다. 흡광도를 635 nm에서 판독하였다.
(b)
결과 및 해석
후보에 대한 비교 결과를 표 26에 제시하였다.
[표 26]
후보에 대한 비교 결과.
효소에 500 μM의 ATP를 첨가하고 시간 경과에 따라 HPLC(아래에 기술된 방법)로 ATP, ADP, AMP의 농도를 분석하여 효소 활성을 측정하였다. 생성된 동역학 곡선을 도 6의 모델에 적합화하여 효소 상수를 얻었다. 효소 상수 Kcat과 관련하여, 효소는 다음의 순서(낮은 활성에서 높은 활성으로)를 보여준다: EP28(wt), EP17, EP14, EP15.
도 7은 EP28에 대한 동역학 데이터 및 모델 적합을 보여준다. 도 8은 EP14에 대한 동역학 데이터 및 모델 적합을 보여준다. 도 9는 EP15에 대한 동역학 데이터 및 모델 적합을 보여준다.
EP28(wt), EP14, EP15 및 EP17에 대한 효소 상수의 개요를 표 27에 제시하였다. 야생형(WT)과 비교하여, 3개의 신규 변이체는 증가된 촉매 활성을 보여준다. 중요한 것은 새로운 변이체들이 촉매 속도 상수(kcat) 및 촉매 효율(kcat/Km)의 뚜렷한 증가를 보여준다는 점이다. 조직 손상 및 혈전증 중의 보고된 ATP 및 ADP 기질 농도가 보고된 Km을 초과하므로, kcat 및 kcat/Km의 이러한 증가는 생체 내에서의 더 높은 활성으로 해석될 가능성이 높을 것이다.
[표 27]
효소 상수
(2)
HPLC 타당성 분석(동역학 및 용량 반응)
(a)
재료 및 방법
후보를 HPLC 타당성 분석으로 시험하였다. 70 μl의 각 샘플을 HPLC용 유리 바이알로 옮겼다.
표 28에 제시된 바와 같이 모액 5 mM로 보정 샘플을 제조하였다.
[표 28]
모액
1000 μM
20 μL의 각 모액을 HPLC 바이알에 혼합하였다.
500 μM
20 μL 1 mM + 20 μL H2O
100 μM
10 μL 1 mM + 90 μL H2O
10 μM
10 μL 100 μM + 90 μL H2O
1 μM
10 μL 10 μM + 90 μL H2O
CapPump(G1376A), 탈기장치(G1379A), ALS(G1329A), Thermostat(G1330B, ColComp (G1316A) 및 DAD(G1315A)를 구비한 Agilent 1100 시스템을 이용하여 HPLC 분리를 수행하였다. 용매 A: 10 mM의 KH2PO4(04243, Riedel-de Ha
n) + 2 mM의 브롬화 TBA, pH 7.0(86857-10G-F, Fluka) 및 용매 B: 10 mM의 KH2PO4 / ACN 1/1 + 2 mM의 브롬화 TBA, pH 5.5. 컬럼: Nucleodur 300-5 C18 ec, 2 x 150 mm, 5 μm, Macherey-Nagel 760185.20 Batch E14100258 36654055. 컬럼 온도는 40℃, 주입 부피는 10 μL, 유속은 0.3 ml/분이었고, 구배는 0~3': 0% B; 3~23': 0~95% B, 선형; 23~28': 95% B, 선형; 28~29': 95~0% B, 선형; 5' 포스트 시간". DAD: 247 nm 및 259 nm.
Waters UPLC I 클래스를 이용하여 UPLC 분리를 수행하였다. 용매 A: 10 mM의 KH2PO4 / 10 mM의 K2HPO4 1/1 + 2 mM의 브롬화 TBA, pH 7.0. 용매 B: 10 mM의 KH2PO4 / ACN 1/1 + 2 mM의 브롬화 TBA, pH 5.5. 컬럼: Fortis Bio C18, 2.1 x 50 mm, 5 μm, di2chrom BIO318-020301 SN H03161210-2. 컬럼 온도는 40℃, 주입 부피는 10 μL, 유속은 0.5 ml/분이었고, 구배는 0~1': 0% B; 1~8': 0~55% B, 선형; 8~10': 55% B; 10~11': 55-0% B, 선형; 14' 정지 시간. DAD는 247 nm 및 259 nm였다.
(b)
결과
결과는 도 7, 8, 9 및 11에서 볼 수 있으며, 상이한 구현예에 따른 후보에 대한 동역학 데이터 및 모델 적합을 보여준다.
10.
실시예 9: 시험관 내 활성, 최초 스크린
이전 실시예에서 기술된 CD39 버전인 EP1 내지 EP24를 IL2-리더가 없고 IL2-출발점이 없는 포유동물 발현 벡터 pRS5a_리더_APP_His(도 5)로 클로닝하였다.
(a)
재료 및 방법
7일 동안 HEK293(PEI-형질감염)에서의 EP-Hit의 소규모 발현(20/50 ml의 규모)을 수행한 후, (위에 기술된 바와 같이) APP-HPLC 상에서의 IPC를 수행하였다.
Ni-NTA-컬럼(0.5 ml CV)을 이용한 15/45 ml의 세포 상청액의 단백질 정제;
6 CV의 IMAC B 완충액(20 mM NaPO4-완충액, 300 mM 이미다졸, pH7.4)을 이용한 용리;
TBS, pH 7.4에서의 정제된 단백질의 농축 및 재완충;
단백질 겔, 분석적 SEC를 이용한 단백질의 분석;
모든 변이체 및 3개의 대조군(IL2-출발점이 있고 없는 모 hCD39-dMIL 또는 EP28, 및 IL2-출발점이 없는 8M-버전)의 전달: TBS, pH 7.4에서의 정제된 단백질 90-200 ul
(b)
결과 및 해석
결과를 아래 표 29에 요약하였다.
모든 샘플은 TBS pH 7.4 중에 있고, APP-(서열번호 247) 및 His-태그(서열번호 249)를 갖는다.
모 인간 CD39ΔMIL(EP28)만이 15개의 아미노산 길이의 IL2-출발점인 aa1-15(서열번호 133)를 갖는다.
파이 방출 분석 BOENKTH1-0252824, 이중 det. 60 및 180분 값
[표 29]
시험관 내 활성
11.
실시예 10: 시험관 내 활성, 개선된 스크린
12종의 돌연변이의 서브세트를 두 번째로 시험하였으나, IL-2 출발점이 더 큰 발현 규모를 허용하였다.
(a)
재료 및 방법
15개의 아미노산 길이의 IL2-출발점인 aa1-15(서열번호 133)가 있는, 포유동물 발현 벡터 pRS5a_리더_APP_His(도 5). 7일 동안 HEK293(PEI-형질감염)에서의 EP-Hit의 소규모 발현(50/100 ml의 규모)에 이은, (위에 기술된 바와 같은) APP-HPLC 상에서의 IPC.
Ni-NTA-컬럼(0.5 ml CV)을 이용한 45/95 ml의 세포 상청액의 단백질 정제
6 CV의 IMAC B 완충액(20 mM NaPO4-완충액, 300 mM 이미다졸, pH 7.4)을 이용한 용리
TBS, pH 7.4에서의 정제된 단백질의 농축 및 재완충,
단백질 겔, 분석적 SEC를 이용한 단백질의 분석
모든 변이체 및 대조군(IL2-출발점 aa1-15(서열번호 133)가 있는, 모 hCD39-dMIL, 또는 EP28)의 전달:
500 ul의 TBS, pH7.4 중의 정제된 단백질
(b)
결과 및 해석
결과를 아래 표 30, 표 32 및 표 33에 요약하였다.
[표 30]
EP-Hit 2016.07.06의 단백질 정제, 파트 1
[표 31]
EP-Hit 2016.07.06의 단백질 정제, 파트 2
[표 32]
단백질 정제 EP-Hit 2016.07.15
[표 33]
서열번호 1에 따른 야생형 CD39 서열과 관련된 점 돌연변이.
12.
실시예 11: 생체 내 활성, pK
(a)
재료 및 방법
생체 내 PK의 경우, PBS 완충액 중 10 mg/ml의 최종 농도의 10 mg/kg 화합물을 꼬리 정맥을 통해 4마리의 의식이 있는 암컷 C57BL/6 마우스에게 정맥 내(1 ml/kg)로 투여하였다. 마우스는 WIGA에서 입수하였고, 체중이 약 22 g이었다. 모든 생애 연구는 스위스 동물복지법에 따라 수행되었다.
POCT Minivette을 사용하여 적은 부피의 혈청 튜브에 투약 후 0.25, 3, 8, 24 및 48시간 후에 전혈을 수집하였다(시간당 50 μL). 혈청을 분리하여 농도 결정에 사용하였다.
Gyrolab 기술은 원심력 및 레이저 유도 형광 검출을 통해 작동하는 친화도 플로우 스루 형식을 사용하는 나노리터 규모의 자동화된 면역분석이다. 스트렙타비딘 코팅 비드는 Gyrolab Bioaffy CD의 친화도 컬럼에 미리 패킹되어 있다. 각 CD는 112개의 컬럼을 함유한다. 마이크로구조당 친화도 포획 컬럼은 15 nl을 포함한다. 주입된 샘플은 모세관 작용에 의해 들어간다. 비오틴 부착된 포획 시약은 스트렙타비딘 코팅 비드에 결합한다. 그 후, 분석물 용액이 주입되고, 이는 포획된 분자에 결합한다. 마지막으로, 형광단 표지 검출 시약이 적용된다. CD39의 경우, APP 태그의 가용성에 따라 두 가지의 상이한 분석 판독값을 사용하였다.
1) 항-CD39(40035) 및 항-APP(27431)은 도 10a에 도시되어 있다.
2) Fab(40035) 및 항-Fc/항-CD39(40044)의 1:1 프리믹스(모두 EP28aa1-16 구성체)는 도 10b에 도시되어 있다. 항체 40044는 아민 커플링에 의해 비오틴 부착될 때 활성을 잃으므로, 항체 40035만 비오틴을 부착하였다.
CD39 구성체에 대한 모든 표준 곡선을 1:2의 희석 계열로 5% (v/v)의 마우스 혈청을 함유하는 Rexxip A에 희석하였다. APP 태그가 부착된 구성체에 적용된 농도 범위는 5000 ng/ml 내지 9.77 ng/ml이었고, EP28aa1-16의 경우 10000 ng/ml 내지 9.77 ng/ml이었다. 모든 마우스 혈청 샘플을 5% (v/v)의 마우스 혈청을 함유하는 Rexxip A에 1:100으로 희석하였다. CD39 구성체의 QC 샘플을 5% (v/v) 마우스 혈청을 함유하는 Rexxip A에 희석하였다(APP 태그가 있는 구성체의 경우 50 및 500 ng/ml, EP28aa1-16의 경우 500 및 1000 ng/ml). 모든 비오틴 부착된 포획 시약의 최종 농도는 0.1 mg/ml이었고, 형광 표지된 검출 항체는 Rexxip F에 10 nM로 희석되었다.
(b)
결과 및 해석
결과를 표 34에 요약하였다. 보다시피, 모든 후보는 동일한 PK를 보여준다. 따라서, 후보의 선택은 PK 속성을 기초로 하지 않았다.
[표 34]
pK 값
13.
실시예 12: 생체 내 활성, AKI 모델
(a)
재료 및 방법
우측 신장의 신장적출술을 I/R 설정의 시작 전에 수행하였다. 생물학의 전체 역학을 변화시키는 보상 기전을 피하기 위해 두 번째 신장을 제거한다. 자발적으로 호흡하는 마취된 동물을 온혈동물 모니터 시스템의 온혈동물 담요 위에 놓고, 멸균 거즈로 덮는다. 체온을 직장 탐침을 통해 기록하고 저체온증을 방지하기 위해 36.5~37.5℃의 범위에서 조절한다. 동물을 마취시키고, 제모하고, 소독한다(Betaseptic). 중간선 절개/개복술 후, 복부 내용물을 좌측으로 집어넣고, 우측 신장을 제거한다. 요관과 혈관을 분리하고 결찰한 후(9-0 Ethicon), 신장을 제거한다.
I/R 손상 유도: 우측 신장의 신장적출술 직후, 복부 내용물을 우측으로 집어넣고, 좌측 신동맥을 신장 허혈 유도를 위해 자유로이 절개한다.
미세동맥류 클립을 이용하여 육경을 클램핑하여 신장으로 가는 혈류를 차단하고 신장 허혈을 유도한다. 신장 허혈의 지속기간은 클램핑 시간으로부터 시작한다. 성공적인 허혈은 신장의 색이 몇 초 안에 적색에서 진한 보라색으로 변하는 것에 의해 확인된다. 허혈 후, 미세동맥류 클립을 제거하고, 재관류는 신장의 색이 적색으로 변하는 것에 의해 표시된다.
(b)
결과 및 해석
결과를 도 12에 나타내었다. 후보들은 그들의 특정 시험관 내 활성과 관련이 있는 생체 내 용량 반응을 보여준다. 도 12a는 모 EP28에 대한 결과를 보여주고, 도 12b는 EP1xEP17에 대한 결과를 보여주며, 도 12c는 EP14에 대한 결과를 보여준다. 보다시피, EP28 및 EP1xEP17은 유사한 용량 반응을 보이는 반면, 시험관 내 활성이 더 높은 EP14는 더 낮은 용량으로 완전한 효능을 나타낸다.
14.
실시예 13: 역가, 수율 및 개발가능성
선택된 후보를 상업적 규모로 제조하기 위해서는 상대적으로 높은 수율로 이들을 발현시킬 수 있는 것이 중요하다. 치료 단백질의 경우, 고 생산성 클론을 선택할 수 있게 하는 농축 기술의 부족과 더불어 포맷 복잡성으로 인해 치료적 항체에 비해 이는 덜 간단할 수 있다.
두 후보 EP14aa1-3 및 EP28aa1-3은 비슷한 기술적 특성을 가지고 있었으며, 이러한 특성은 도전적이었다. 특히, 초기 발현 배치의 낮은 발현 역가(데이터 미도시)는 생산 비용에 영향을 미치거나 숙주 세포 단백질의 제어가 강력하지 않기 때문에 규모 확대 후에 더 낮을 수도 있다.
두 후보 모두에 대한 초기 클론 선택에 의해 단백질 발현을 개선하기 위해 맞춤형 정제 공정이 요구되었다. 이를 위해 후보 EP28aa1-3 및 EP14aa1-3을 발현하는 세포 풀을 생성하였다.
모 CHO 세포주를 EP28aa1-16/EP14aa1-3 발현 세포주의 생산을 위한 숙주 세포주로 사용하였다. 숙주 세포주는 예컨대, 특허 출원 제WO2015092737호 및 제WO2015092735호(둘 다 전체가 참조로서 포함됨)에 기술된 방식으로, 당업자에게 잘 알려져 있는 CHO-K1 세포주로부터 유래되었다. CHO 세포주로부터의 단일 바이알을 사용하여 EP28aa1-16/EP14aa1-3 재조합 세포주를 제조하였다.
세포를 화학적으로 한정된 배양 배지에서 성장시켰다. EP28aa1-16/EP14aa1-3을 암호화하는 발현 벡터인 SwaI 선형화된 플라스미드 DNA 1 μg을 각 형질감염에 대하여 첨가하였다. 형질감염 반응을 화학적으로 한정된 배양 배지에서 수행하였다.
제조사의 지시에 따라 AMAXA 유전자 펄서를 사용하여 전기천공에 의해 형질감염을 수행하였다. 형질감염에 사용된 모 CHO 세포는 지수 성장기에 있었고, 세포 생존률은 95%를 초과하였다. 전체로서, 형질감염당 5x106개 세포로 3회의 형질감염을 수행하였다. 형질감염 직후, 세포를 화학적으로 한정된 배양 배지를 함유하는 쉐이크 플라스크로 옮겼다.
선택 과정을 시작하기 전에 세포 풀을 36.5℃ 및 10% CO2에서 48시간 동안 배양하였다. 발현 벡터에 암호화된 선택 마커를 사용하여 선택 절차를 수행하였다. 형질감염 및 저 엽산염 조건 하에서의 성장 48시간 후, 화학적으로 한정된 배양 배지에 10 nM MTX를 첨가하여 추가의 선택적 압력을 가하였다. MTX 선택 개시 21일 후, 주로 MTX 내성 세포로 구성된 풀 집단이 출현하였다. 풀 회수 후 세포를 냉동시켰다. EP28aa1-16/EP14aa1-3의 농도 측정을 위하여 화학적으로 한정된 배양 배지에서 표준 공급형 배치를 준비하였다. 역상 크로마토그래피(RPC)를 이용하여 생성물 농도를 결정하였다. EP28aa1-16/EP14aa1-3을 생산하는 CHO 세포 풀을 FACS 단일 세포 분류/세포 프린터 절차에 사용하여 개별화된 클론성 세포주를 수득하였다.
15.
실시예 14: 치료적 용도
P2X7R을 활성화시키는 세포 외 ATP는 이식편 대 숙주 질환을 강화하는 것과 같이, 여러 질환과 명백하게 관련이 있었다(문헌[Wilhelm et al. Graft-versus-host disease is enhanced by extracellular ATP activating P2X7R. Nature Medicine 16:12, pages 1434-1439 (2010)].)
또한, 시험관 내 및 생체 내 연구 모두 CD39가 ADP의 수준을 조절하여 심혈관 건강에서 중요한 아피라제를 나타냄을 보여준다. 아피라제는 세포 외 ADP를 대사하여 혈소판 응집을 억제하는 것으로 알려져 있다.
인간 아피라제는 혈소판의 ADP 수용체에 비가역적으로 결합하는 클로피도그렐(PlavixTM)과 같은 다른 요법과 달리 혈소판에 공유 결합하지 않는다. 이는 치료적 차단의 더 빠른 소실을 가능하게 하고, 따라서 과도한 혈소판 활성화를 나타내는 환자로의 더욱 안전한 접근을 가능하게 한다. 이는 과도한 혈소판 활성화를 나타내는 환자에 대한 더욱 안전한 접근을 제공한다.
따라서, 본 발명에 따른 화합물과 같은, 세포 외 ATP의 수준을 감소시키는 화합물의 치료적 용도에 대한 명확한 근거가 있다.
본 발명에 따른 화합물의 치료적 용도의 구체적인 비 제한적 예는 외상 및/또는 저산소증으로 인한 급성 기관 손상, 예컨대, 급성 호흡 곤란 증후군(ARDS), 폐 손상, 신부전, 급성 신장 손상(AKI)(관상 동맥 우회로 이식 수술 후의 급성 신장 손상 포함), 신장 또는 기타 고형 장기의 이식(이종이식 포함) 후 지연 이식편 기능, 또는 혈관 질환, 예컨대, 폐쇄성 혈관 질환, 이식, 및 이종이식, 뇌졸중, 관상 동맥 질환 또는 심근경색으로 인한 손상, 죽상 동맥경화증, 동맥경화증, 색전증, 자간전증, 혈관성형술, 혈관 손상, 이식, 신생아 저산소성 허혈성 뇌병증, 혈소판 관련 허혈성 장애(폐 허혈, 관상동맥 허혈 및 뇌 허혈 포함), 허혈-재관류 손상(IRI) 혈전성 장애(관상 동맥 혈전증, 뇌 대동맥 혈전증, 심장 내 혈전증, 말초 동맥 혈전증, 및 정맥 혈전증 포함), 신장 또는 기타 고형 장기의 이식(이종이식 포함) 후 지연 이식편 기능을 앓는 개체의 치료이다. 본 발명에 따른 화합물의 치료적 용도의 다른 비 제한적인 예는 화상 또는 방사선 손상, 패혈증의 치료, 상처 치유 개선, 출혈 또는 출혈 위험 감소, 기관 손상, 이식편 대 숙주 빌환의 예방, 또는 이식 거부의 예방이다.
본 발명에 다른 화합물의 특히 바람직한 치료적 용도는 급성 신장 손상(AKI), 예컨대, 관상 동맥 우회로 이식 수술 후의 급성 신장 손상 또는 패혈증 또는 횡문근 융해이다. 이 병태는 환자의 사망률을 증가시키고, 표준 치료(SoC)가 없다. 중환자실의 AKI의 주요 원인은 다음과 같다: 패혈증(47.5%), 대수술(34%), 심장성 쇼크(27%), 저혈량증(26%) 및 신독성 화합물(19%). 또한, AKI는 만성 신장 질환(CKD) 발병의 독립적인 강력한 위험 인자이다. 주요 심장 수술 환자의 20~30%가 급성 신장 손상을 입는다. 또 다른 바람직한 구현예는 심장 수술 관련 급성 신장 손상의 치료를 위한 본 발명에 따른 단리된 아피라제의 용도에 관한 것이다.
또 다른 구현예에서, 본 개시는 지연 이식편 기능(DGF), 급성 호흡 곤란 증후군(ARDS), 급성 심근 경색(AMI), 외상성 뇌 손상(TBI)/급성 허혈 뇌졸중(AIS), 또는 종종 다기관 부전(MOF)으로 지칭되는 이들의 조합의 치료에 사용하기 위한 본 발명에 따른 단리된 아피라제에 관한 것이다.
16.
급성 신장 손상(AKI)은 패혈증의 일반적인 합병증이다. 패혈증 환자의 28%가 AKI를 얻는다. 추가의 바람직한 구현예에서, 본 개시는 패혈증 관련 급성 신장 손상의 치료를 위한 본 발명에 따른 단리된 아피라제의 용도에 관한 것이다. 실시예 15: 치료 조성물
치료 단백질은 일반적으로, 투여 준비된 수성 형태로 또는 투여 전에 적합한 희석제로 재구성하기 위한 동결건조물로서 제형화된다. 단백질은 동결건조물로서, 또는 예를 들어, 사전 충전된 시린지 내의 수성 조성물로서 제형화될 수 있다.
적합한 제형은 수성 제약 조성물 또는 환자에게 전달하기 위하여 고농도의 치료 단백질 활성 성분 및 낮은 수준의 단백질 응집물을 갖는 용액을 제공하도록 재구성될 수 있는 동결건조물을 제공할 수 있다. 고농도의 단백질은 환자에게 전달되어야 하는 물질의 양(용량)을 감소시킬 수 있으므로 유용하다. 감소된 투약 부피는 고정된 용량을 환자에게 전달하는 데 소요되는 시간을 최소화한다. 고농도의 단백질을 갖는 본 발명의 수성 조성물은 피하 투여에 특히 적합하다.
따라서, 본 발명은 치료 단백질을 포함하는, 대상체에서의 투여, 예를 들어 피하 투여에 적합한 수성 제약 조성물을 제공한다.
치료 단백질은 제약상 허용 가능한 담체와 조합될 때 제약 조성물로서 사용될 수 있다. 이러한 조성물은, 치료 단백질 이외에, 담체, 다양한 희석제, 충전제, 염, 완충액, 안정화제, 가용화제 및 당해 분야에 알려진 다른 물질을 함유할 수 있다. 담체의 특성은 투여 경로에 따라 달라질 것이다. 개시된 방법에 사용하기 위한 제약 조성물은 특정 표적 장애의 치료를 위한 추가적인 치료제를 또한 함유할 수 있다.
17.
실시예 16: 투여 경로
일반적으로, 본 발명에 따른 단백질은 예를 들어 정맥 내, 복강 내 또는 피하 주사에 의해 투여된다. 이러한 투여를 수행하는 방법은 당업자에게 알려져 있다. 국소 또는 경구 투여될 수 있거나 점막을 통해 전달될 수 있는 조성물을 수득할 수도 있다. 당업자가 이해하는 바와 같이, 임의의 적합한 투여 수단이 특정의 선택된 투여 경로에 적절하게 사용될 수 있다.
가능한 투여 경로의 예는 비경구(예를 들어, 정맥 내(I.V. 또는 IV), 근육 내(IM), 피내, 피하(S.C. 또는 SC) 또는 주입), 경구 및 폐(예를 들어, 흡입), 코, 경피(국소), 경점막, 동맥 내, 연속 주입, 및 직장 투여를 포함한다. 비경구, 피내, 또는 피하 적용에 사용되는 용액 또는 현탁액에는 다음의 성분이 포함될 수 있다: 멸균 희석제, 예컨대 주사용수, 식염수 용액, 고정유, 폴리에틸렌 글리콜, 글리세린, 프로필렌 글리콜 또는 기타 합성 용매; 항균제, 예컨대 벤질 알코올 또는 메틸 파라벤; 항산화제, 예컨대 아스코르브산 또는 중아황산나트륨; 킬레이트화제, 예컨대 에틸렌디아민테트라아세트산; 완충제, 예컨대 아세테이트, 시트레이트 또는 포스페이트 및 긴장성 조정제, 예컨대 염화나트륨 또는 덱스트로스. pH는 산 또는 염기, 예컨대 염산 또는 수산화나트륨으로 조정될 수 있다. 비경구 제제는 유리 또는 플라스틱으로 제조된 앰플, 일회용 시린지, 또는 다회 용량 바이알에 봉입될 수 있다.
아피라제 요법은 치료법을 필요로 하는 대상체에게 본 발명에 따른 단백질의 "로딩 용량"을 투여함으로써 개시될 수 있다. "로딩 용량"은 대상체에게 투여되는 본 발명에 따른 단백질의 초기 용량을 의미하며, 여기서 투여되는 본 발명에 따른 단백질의 용량은 더 높은 용량 범위 내에 속한다. "로딩 용량"은 완전한 "로딩 용량"이 약 24시간 내에(또는 질환의 중증도에 따라 여러 번 정맥 내 투여가 필요한 경우 첫 달 내에) 투여되는 한, 단회 투여, 예를 들어 단백질이 IV 투여되는 단회 주입으로 투여되거나, 다회 투여, 예를 들어 단백질이 IV 투여되는 다회 주입으로 투여될 수 있다. "로딩 용량"의 투여 후, 대상체는 이어서 본 발명에 따른 단백질의 하나 이상의 추가 치료 유효 용량을 투여 받는다. 후속 치료 유효 용량은, 예를 들어 매주의 투약 일정에 따라, 또는 2주에 1회, 3주에 1회, 또는 4주에 1회 투여될 수 있다. 이러한 구현예에서, 후속의 치료 유효 용량은 일반적으로 더 낮은 용량 범위 내에 속한다.
대안적으로, 일부 구현예에서, "로딩 용량" 후, 후속적인 치료 유효 용량의 본 발명에 따른 단백질은 "유지 일정"에 따라 투여되며, 치료 유효 용량의 본 발명에 따른 단백질은 월 1회, 6주에 1회, 2개월에 1회, 10주에 1회, 3개월에 1회, 14주에 1회, 4개월에 1회, 18주에 1회, 5개월에 1회, 22주에 1회, 6개월에 1회, 7개월에 1회, 8개월에 1회, 9개월에 1회, 10개월에 1회, 11개월에 1회, 또는 12개월에 1회 투여된다. 이러한 구현예에서, 본 발명에 따른 단백질의 치료 유효 용량은, 특히 후속 용량이 더 빈번한 간격으로(예를 들어, 2주에 1회 내지 월 1회) 투여될 경우 더 낮은 투약 범위 내이거나, 특히 후속 용량이 덜 빈번한 간격으로 투여될 경우(예를 들어, 후속 용량이 1개월 내지 12개월 간격으로 투여될 경우) 더 높은 투약 범위 내에 속한다.
일반적으로 투약 시기는 "기준선"으로도 알려져 있는, 활성 화합물의 첫 번째 투여일로부터 측정된다. 그러나 의료인마다 상이한 명명 규칙을 사용한다.
특히, 0주차는 일부 의료인에 의해 1주차로 지칭될 수 있는 한편, 0일차는 일부 의료인에 의해 1일차로 지칭될 수 있다. 따라서, 동일한 투약 일정을 지칭하면서, 예를 들어 의사마다 용량을 3주차/21일차, 3주차/22일차, 4주차/21일차, 4주차/22일차에 제공되는 것으로 지정하는 것이 가능하다. 일관성을 위해, 본원에서는 투약의 첫째 주를 0주차로 지칭하고, 투약의 첫째 날을 1일차로 지칭한다. 그러나 이 명명 규칙은 단순히 일관성을 위해 사용되며, 제한적인 것으로 해석되어서는 안 된다는 점은 당업자가 이해할 것이다. 즉, 의사가 특정 주를 "1주차" 또는 "2주차"라 지칭하는지에 관계없이 매주의 투약은 단백질의 매주 용량을 제공하는 것이다. 본원에 언급된 투여 요법의 예는 도 1 및 도 2에서 확인된다. 용량은 정확한 시점에 제공될 필요가 없으며, 예를 들어 대략 29일차에 예정된 용량은 적절한 주에 제공되는 한, 예를 들어 24일차 내지 34일차에, 예를 들어 30일차에 제공될 수 있음이 이해될 것이다.
본원에 사용된 어구 "[표시된 용량]의 전달을 허용하기에 충분한 양의 단백질을 갖는 용기"는 주어진 용기(예를 들어, 바이알, 펜, 시린지) 내에 원하는 용량을 제공하는 데 사용될 수 있는 부피의 (예를 들어, 제약 조성물의 일부로서) 단백질이 배치되어 있음을 의미하기 위해 사용된다. 일례로서, 원하는 용량이 500 mg이면, 임상의는 농도가 250 mg/ml인 단백질 제형을 함유하는 용기로부터의 2 ml, 농도가 500 mg/ml인 단백질 제형을 함유하는 용기로부터의 1 ml, 농도가 1000 mg/ml인 단백질 제형을 함유하는 용기로부터의 0.5 ml 등을 사용할 수 있다. 이러한 각각의 경우, 이들 용기는 원하는 500 mg의 용량의 전달을 허용하기에 충분한 양의 단백질을 갖는다.
본원에서 사용되는 어구 "[표시된 용량]의 [투여 경로] 전달을 허용하는 투여량으로 제형화된"은 주어진 제약 조성물이 표시된 투여 경로(예를 들어, s.c. 또는 i.v.)를 통해 원하는 용량의 단백질을 제공하는 데 사용될 수 있음을 의미하는 데 사용된다. 일례로서, 원하는 피하 용량이 500 mg이면, 임상의는 250 mg/ml 농도의 단백질 제형 2 ml, 500 mg/ml 농도의 단백질 제형 1 ml, 1000 mg/ml 농도의 단백질 제형 0.5 ml 등을 사용할 수 있다. 이러한 각각의 경우, 이들 단백질 제형은 단백질의 피하 전달을 허용하기에 충분히 높은 농도이다. 피하 전달은 전형적으로 약 2 ml 미만의 부피, 바람직하게는 약 1 ml 이하의 부피의 전달을 필요로 한다. 그러나 예를 들어 패치/펌프 메커니즘을 이용해 더 많은 부피가 시간이 지남에 따라 전달될 수 있다.
환자에서 조직 손상의 치료용 의약의 제조를 위한 단백질의 용도가 본원에 개시되며, 이러한 의약은 용기를 포함하도록 제형화되며, 각각의 용기는 단위 용량당 적어도 약 75 mg, 150 mg, 300 mg 또는 600 mg의 단백질의 전달을 허용하기에 충분한 양의 단백질을 갖는다.
환자에서 조직 손상의 치료용 의약의 제조를 위한 단백질의 용도가 본원에 개시되며, 이러한 의약은 단위 용량당 75 mg, 150 mg, 300 mg 또는 600 mg의 단백질의 전신 전달(예를 들어, i.v. 또는 s.c. 전달)을 허용하는 투여량으로 제형화된다.
18.
실시예 17: 키트
또한, 본 개시는 (경우에 따라) 조직 손상이 있는 환자를 단백질로 치료하기 위한 키트를 포함한다. 이러한 키트는 (예를 들어, 액체 또는 동결건조 형태의) 단백질 또는 (위에 기술된) 단백질을 포함하는 제약 조성물을 포함한다. 추가로, 이러한 키트는 단백질을 투여하기 위한 수단(예를 들어, 시린지 및 바이알, 사전 충전된 시린지, 사전 충전된 펜, 패치/펌프) 및 사용 지침을 포함할 수 있다. 지침은 특정 투약 요법의 일부로서 환자에게 단백질을 제공하는 것을 개시할 수 있다. 이들 키트는 또한 예를 들어, 봉입된 단백질과 함께 전달하기 위한, 건선 치료용 (위에 기술된) 추가 치료제를 포함할 수 있다.
어구 "투여하기 위한 수단"은 환자에게 약물을 전신 투여하기 위해 이용 가능한 임의의 도구(사전 충전된 시린지, 바이알 및 시린지, 주사 펜, 자동주사기, i.v. 드립 및 백, 펌프, 패치/펌프 등을 포함하나 이에 한정되지 않음)를 나타내기 위해 사용된다. 이러한 물품을 이용해, 환자가 약물을 자가 투여(즉, 스스로 약물을 투여)할 수 있거나, 간병인 또는 의사가 약물을 투여할 수 있다.
조직 손상이 있는 환자의 치료를 위한 키트가 본원에 개시되며, 키트는 a) 치료적 유효량의 단백질을 포함하는 제약 조성물; b) 환자에게 단백질을 투여하기 위한 수단; 및 c) 이를 필요로 하는 환자에게 단백질을 피하 투여하는 것을 제공하는 지침을 포함한다.
서열 표
본 발명을 실시하는 데 유용한 아미노산 및 뉴클레오티드 서열을 표 35에 개시하였다.
[표 35]
본 발명을 실시하는 데 유용한 서열
SEQUENCE LISTING
<110> NOVARTIS AG
<120> SOLUBILIZED APYRASES, METHODS AND USE
<130> PAT057510-EP-EPA
<140> EP 18184269.1
<141> 2018-07-18
<160> 253
<170> PatentIn version 3.5
<210> 1
<211> 510
<212> PRT
<213> Homo sapiens
<400> 1
Met Glu Asp Thr Lys Glu Ser Asn Val Lys Thr Phe Cys Ser Lys Asn
1 5 10 15
Ile Leu Ala Ile Leu Gly Phe Ser Ser Ile Ile Ala Val Ile Ala Leu
20 25 30
Leu Ala Val Gly Leu Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys
35 40 45
Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile
50 55 60
Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His Gln
65 70 75 80
Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln
85 90 95
Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala
100 105 110
Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu
115 120 125
Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu
130 135 140
Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro
145 150 155 160
Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala
165 170 175
Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys
180 185 190
Thr Arg Trp Phe Ser Ile Val Pro Tyr Glu Thr Asn Asn Gln Glu Thr
195 200 205
Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val
210 215 220
Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg
225 230 235 240
Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr
245 250 255
Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val
260 265 270
Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys
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Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg
290 295 300
Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly
305 310 315 320
Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser
325 330 335
Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro
340 345 350
Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys
355 360 365
Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu
370 375 380
Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser
385 390 395 400
Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly
405 410 415
Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp
420 425 430
Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala
435 440 445
Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala
450 455 460
Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr Tyr Val Phe Leu
465 470 475 480
Met Val Leu Phe Ser Leu Val Leu Phe Thr Val Ala Ile Ile Gly Leu
485 490 495
Leu Ile Phe His Lys Pro Ser Tyr Phe Trp Lys Asp Met Val
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<210> 2
<211> 511
<212> PRT
<213> Rattus norvegicus
<400> 2
Met Glu Asp Ile Lys Asp Ser Lys Val Lys Arg Phe Cys Ser Lys Asn
1 5 10 15
Ile Leu Ile Ile Leu Gly Phe Ser Ser Val Leu Ala Val Ile Ala Leu
20 25 30
Ile Ala Val Gly Leu Thr His Asn Lys Pro Leu Pro Glu Asn Val Lys
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Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Asn Leu Tyr Ile
50 55 60
Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val Gln Leu
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Leu Glu Glu Cys Gln Val Lys Gly Pro Gly Ile Ser Lys Tyr Ala Gln
85 90 95
Lys Thr Asp Glu Ile Ala Ala Tyr Leu Ala Glu Cys Met Lys Met Ser
100 105 110
Thr Glu Arg Ile Pro Ala Ser Lys Gln His Gln Thr Pro Val Tyr Leu
115 120 125
Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Lys Gln Ser
130 135 140
Ala Asp Glu Val Leu Ala Ala Val Ser Arg Ser Leu Lys Ser Tyr Pro
145 150 155 160
Phe Asp Phe Gln Gly Ala Lys Ile Ile Thr Gly Gln Glu Glu Gly Ala
165 170 175
Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Arg Phe Thr Gln Glu
180 185 190
Gln Ser Trp Leu Asn Phe Ile Ser Asp Ser Gln Lys Gln Ala Thr Phe
195 200 205
Gly Ala Leu Asp Leu Gly Gly Ser Ser Thr Gln Val Thr Phe Val Pro
210 215 220
Leu Asn Gln Thr Leu Glu Ala Pro Glu Thr Ser Leu Gln Phe Arg Leu
225 230 235 240
Tyr Gly Thr Asp Tyr Thr Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
245 250 255
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Gln Asp Ile Gln Val Ser
260 265 270
Ser Gly Gly Ile Leu Lys Asp Pro Cys Phe Tyr Pro Gly Tyr Lys Lys
275 280 285
Val Val Asn Val Ser Glu Leu Tyr Gly Thr Pro Cys Thr Lys Arg Phe
290 295 300
Glu Lys Lys Leu Pro Phe Asn Gln Phe Gln Val Gln Gly Thr Gly Asp
305 310 315 320
Tyr Glu Gln Cys His Gln Ser Ile Leu Lys Phe Phe Asn Asn Ser His
325 330 335
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Val Phe Leu Pro Pro Leu
340 345 350
Gln Gly Ser Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Asp Phe
355 360 365
Phe Lys Lys Met Ala Asn Asp Ser Val Ser Ser Gln Glu Lys Met Thr
370 375 380
Glu Ile Thr Lys Asn Phe Cys Ser Lys Pro Trp Glu Glu Val Lys Ala
385 390 395 400
Ser Tyr Pro Thr Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser
405 410 415
Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr Asn Phe Thr Gly
420 425 430
Thr Ser Trp Asp Gln Ile His Phe Met Gly Lys Ile Lys Asp Ser Asn
435 440 445
Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro
450 455 460
Ala Glu Gln Pro Leu Ser Pro Pro Leu Pro His Ser Thr Tyr Ile Ser
465 470 475 480
Leu Met Val Leu Phe Ser Leu Val Leu Val Ala Met Val Ile Thr Gly
485 490 495
Leu Phe Ile Phe Ser Lys Pro Ser Tyr Phe Trp Lys Glu Ala Val
500 505 510
<210> 3
<211> 441
<212> PRT
<213> Homo sapiens
<400> 3
Gln Ile His Lys Gln Glu Val Leu Pro Pro Gly Leu Lys Tyr Gly Ile
1 5 10 15
Val Leu Asp Ala Gly Ser Ser Arg Thr Thr Val Tyr Val Tyr Gln Trp
20 25 30
Pro Ala Glu Lys Glu Asn Asn Thr Gly Val Val Ser Gln Thr Phe Lys
35 40 45
Cys Ser Val Lys Gly Ser Gly Ile Ser Ser Tyr Gly Asn Asn Pro Gln
50 55 60
Asp Val Pro Arg Ala Phe Glu Glu Cys Met Gln Lys Val Lys Gly Gln
65 70 75 80
Val Pro Ser His Leu His Gly Ser Thr Pro Ile His Leu Gly Ala Thr
85 90 95
Ala Gly Met Arg Leu Leu Arg Leu Gln Asn Glu Thr Ala Ala Asn Glu
100 105 110
Val Leu Glu Ser Ile Gln Ser Tyr Phe Lys Ser Gln Pro Phe Asp Phe
115 120 125
Arg Gly Ala Gln Ile Ile Ser Gly Gln Glu Glu Gly Val Tyr Gly Trp
130 135 140
Ile Thr Ala Asn Tyr Leu Met Gly Asn Phe Leu Glu Lys Asn Leu Trp
145 150 155 160
His Met Trp Val His Pro His Gly Val Glu Thr Thr Gly Ala Leu Asp
165 170 175
Leu Gly Gly Ala Ser Thr Gln Ile Ser Phe Val Ala Gly Glu Lys Met
180 185 190
Asp Leu Asn Thr Ser Asp Ile Met Gln Val Ser Leu Tyr Gly Tyr Val
195 200 205
Tyr Thr Leu Tyr Thr His Ser Phe Gln Cys Tyr Gly Arg Asn Glu Ala
210 215 220
Glu Lys Lys Phe Leu Ala Met Leu Leu Gln Asn Ser Pro Thr Lys Asn
225 230 235 240
His Leu Thr Asn Pro Cys Tyr Pro Arg Asp Tyr Ser Ile Ser Phe Thr
245 250 255
Met Gly His Val Phe Asp Ser Leu Cys Thr Val Asp Gln Arg Pro Glu
260 265 270
Ser Tyr Asn Pro Asn Asp Val Ile Thr Phe Glu Gly Thr Gly Asp Pro
275 280 285
Ser Leu Cys Lys Glu Lys Val Ala Ser Ile Phe Asp Phe Lys Ala Cys
290 295 300
His Asp Gln Glu Thr Cys Ser Phe Asp Gly Val Tyr Gln Pro Lys Ile
305 310 315 320
Lys Gly Pro Phe Val Ala Phe Ala Gly Phe Tyr Tyr Thr Ala Ser Ala
325 330 335
Leu Asn Leu Ser Gly Ser Phe Ser Leu Asp Thr Phe Asn Ser Ser Thr
340 345 350
Trp Asn Phe Cys Ser Gln Asn Trp Ser Gln Leu Pro Leu Leu Leu Pro
355 360 365
Lys Phe Asp Glu Val Tyr Ala Arg Ser Tyr Cys Phe Ser Ala Asn Tyr
370 375 380
Ile Tyr His Leu Phe Val Asn Gly Tyr Lys Phe Thr Glu Glu Thr Trp
385 390 395 400
Pro Gln Ile His Phe Glu Lys Glu Val Gly Asn Ser Ser Ile Ala Trp
405 410 415
Ser Leu Gly Tyr Met Leu Ser Leu Thr Asn Gln Ile Pro Ala Glu Ser
420 425 430
Pro Leu Ile Arg Leu Pro Ile Glu Pro
435 440
<210> 4
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 4
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 5
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 5
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 6
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 6
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 7
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 7
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccatgga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 8
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 8
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Met
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 9
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 9
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccatgga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgatggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccaaggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 10
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 10
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Gly Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Arg Thr Pro Leu Ser His Ser Thr
420 425
<210> 11
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 11
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccatgga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agggattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgcgc 1260
acacctctga gccacagcac c 1281
<210> 12
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 12
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Ala Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Arg Thr Pro Leu Ser His Ser Thr
420 425
<210> 13
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 13
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgcgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccatgga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagg 1260
acacctctga gccacagcac c 1281
<210> 14
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 14
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Met
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Asp Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 15
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 15
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgatggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcgacaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 16
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 16
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Ser Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Met
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Arg Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 17
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 17
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatctc cctgaccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgatggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgc ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 18
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 18
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Glu Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Ser Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Ala Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Thr Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 19
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 19
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgagg aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgtccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg cggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcacc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 20
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 20
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Ala Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 21
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 21
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgattccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg cggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggt aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtagtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
ccattccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 22
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 22
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Arg Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 23
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 23
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctga ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 24
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 24
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Thr Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 25
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 25
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta tggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcacc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcctttgagc 1260
acacctctga gccacagcac c 1281
<210> 26
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 26
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Thr Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 27
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 27
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccatgga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcacc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960
ctgaacctga ctagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 28
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 28
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Asp Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Thr Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 29
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 29
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga tatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcacc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 30
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 30
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Ser Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Pro Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 31
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 31
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctactccgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgccgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 32
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 32
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Ser Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 33
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 33
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccttgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctactccgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gttacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 34
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 34
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Lys Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Ser Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Pro Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Ser Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 35
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 35
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggcgctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaagg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgccca tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctactccgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgccgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatct ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 36
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 36
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Asn Glu Lys Tyr Leu Ser Glu Phe Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 37
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 37
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccaac cctgggagga aatcaagacc tcctacgctg gcgtgaacga gaagtacctg 1080
agcgagtttt gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 38
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 38
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Phe Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 39
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 39
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtttt gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 40
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 40
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Asp Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 41
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 41
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcgacatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgcagcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 42
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 42
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu Asp Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 43
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 43
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgcagcaggg ctaccacttc 1140
accgccgata gctgggagga catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 44
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 44
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Gly Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Ser Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 45
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 45
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacgg gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccactcc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 46
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 46
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Arg Thr Pro Leu Ser His Ser Thr
420 425
<210> 47
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 47
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccatgga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgcgc 1260
acacctctga gccacagcac c 1281
<210> 48
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 48
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Gly Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Gly Thr Pro Leu Ser His Ser Thr
420 425
<210> 49
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 49
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacgg gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgtt gaatctgacc aacatgatcc ccgccgagca gcccctgggc 1260
acacctctga gccacagcac c 1281
<210> 50
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 50
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Met Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Arg Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Ser Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Arg Thr Pro Leu Ser His Ser Thr
420 425
<210> 51
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 51
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttatgtgcta cggaaaggac caggctctga ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgtacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccactcc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgaga 1260
acacctctga gccacagcac c 1281
<210> 52
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 52
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Lys Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Asn His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 53
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 53
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaagga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgcagcaggg ctaccacttc 1140
accgccgata gctgggagca caaccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 54
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 54
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Asn Glu Lys Tyr Leu Ser Glu Phe Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 55
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 55
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccatgga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccaac cctgggagga aatcaagacc tcctacgctg gcgtgaacga gaagtacctg 1080
agcgagtttt gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 56
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 56
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Phe Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 57
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 57
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccatgga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtttt gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 58
<211> 430
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 58
Ala Pro Thr Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly
1 5 10 15
Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys
20 25 30
Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu
35 40 45
Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val
50 55 60
Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu
65 70 75 80
Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala
85 90 95
Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp
100 105 110
Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp
115 120 125
Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly
130 135 140
Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln
145 150 155 160
Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr
165 170 175
Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln
180 185 190
Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu
195 200 205
Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile
210 215 220
Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly
225 230 235 240
Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr
245 250 255
Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly
260 265 270
Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn
275 280 285
Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu
290 295 300
Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val
305 310 315 320
Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val
325 330 335
Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys
340 345 350
Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe
355 360 365
Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr
370 375 380
Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser
385 390 395 400
Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile
405 410 415
Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425 430
<210> 59
<211> 1290
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 59
gcccctacca cccagaacaa ggccctgccc gagaacgtga agtacggcat cgtgctggac 60
gccggctcct cccacacctc cctgtacatc tacaagtggc ctgccgagaa agaaaacgac 120
accggcgtgg tgcaccaagt ggaagagtgc agagtgaagg gccccggcat ctccaagttc 180
gtgcagaaag tgaacgagat cggcatctac ctgaccgact gcatggaacg ggccagagaa 240
gtgatccctc ggtcccagca ccaggaaacc cctgtctacc tgggcgccac cgccggcatg 300
cggctgctgc ggatggaatc cgaggaactg gccgaccggg tgctggacgt ggtggaacgg 360
tccctgtcca actacccatt cgattttcaa ggcgccagaa tcatcaccgg ccaggaagag 420
ggcgcctacg gctggatcac catcaactac ctgctgggca agttctccca gaagaatcag 480
gaaaccttcg gcgccctgga cctgggcgga gccagcaccc aagtcacatt cgtgccccag 540
aaccagacca tcgagagccc cgacaacgcc ctgcagttcc ggctgtacgg caaggactac 600
aacgtgtaca cccacagctt tctgtgctac ggcaaggacc aggccctgtg gcagaagctg 660
gccaaggaca tccaagtggc ctccaacgag atcctgcggg acccctgctt ccaccccggc 720
tacaagaaag tggtcaacgt gtccgacctg tacaagaccc cttgcaccaa gagattcgag 780
atgaccctgc ccttccagca gttcgagatc cagggcatcg gcaactacca gcagtgccac 840
cagtccatcc tggaactgtt caacacctcc tactgcccct actcccagtg cgccttcaac 900
ggcatcttcc tgcctccact gcagggcgac ttcggcgcct tctccgcctt ctacttcgtg 960
atgaagttcc tgaacctgac ctccgagaaa gtgtcccagg aaaaagtgac cgagatgatg 1020
aagaagttct gcgcccagcc ctgggaggaa atcaagacct cctacgctgg cgtgaaagag 1080
aagtacctgt ccgagtactg cttctccggc acctacatcc tgtccctgct gctgcagggc 1140
taccacttca ccgccgacag ctgggagcac atccacttca tcggcaagat ccagggatcc 1200
gacgctggct ggaccctggg ctacatgctg aatctgacca acatgatccc cgccgagcag 1260
cccctgtcca cccctctgtc tcactccacc 1290
<210> 60
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 60
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Ser Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Phe Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 61
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 61
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccttgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctactccgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtttt gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gttacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 62
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 62
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Thr Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu Asp Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 63
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 63
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcacc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgcagcaggg ctaccacttc 1140
accgccgata gctgggagga catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 64
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 64
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Ser Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 65
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 65
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccttgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctactccgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgcagcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gttacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 66
<211> 442
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 66
Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Thr Ser Ser Thr
1 5 10 15
Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu Asp
20 25 30
Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala Glu
35 40 45
Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg Val
50 55 60
Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile Gly
65 70 75 80
Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro Arg
85 90 95
Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly Met
100 105 110
Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu Asp
115 120 125
Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly Ala
130 135 140
Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr Ile
145 150 155 160
Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe Gly
165 170 175
Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro Gln
180 185 190
Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu Tyr
195 200 205
Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly Lys
210 215 220
Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala Ser
225 230 235 240
Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys Val
245 250 255
Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe Glu
260 265 270
Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn Tyr
275 280 285
Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr Cys
290 295 300
Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu Gln
305 310 315 320
Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe Leu
325 330 335
Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met Met
340 345 350
Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr Ala
355 360 365
Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr Tyr
370 375 380
Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser Trp
385 390 395 400
Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly Trp
405 410 415
Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu Gln
420 425 430
Pro Leu Ser Thr Pro Leu Ser His Ser Thr
435 440
<210> 67
<211> 1326
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 67
gcccctacca gcagcagcac caagaaaacc cagctgacca gcagcaccca gaacaaggcc 60
ctgcccgaga acgtgaagta cggcatcgtg ctggatgccg gcagcagcca caccagcctg 120
tacatctaca agtggcctgc cgagaaagaa aacgacaccg gcgtggtgca tcaggtggaa 180
gagtgcagag tgaagggccc tggcatcagc aagttcgtgc agaaagtgaa cgagatcggc 240
atctacctga ccgactgcat ggaacgggcc agggaagtga tccccagaag ccagcaccag 300
gaaacccccg tgtatctggg agccaccgcc ggcatgagac tgctgagaat ggaaagcgag 360
gaactggccg accgggtgct ggacgtggtg gaaagaagcc tgagcaacta cccattcgat 420
tttcaaggcg ccagaatcat caccggccag gaagaaggcg cctacggctg gatcaccatc 480
aactacctgc tgggcaagtt cagccagaag aatcaggaaa ccttcggcgc cctggacctg 540
ggcggagctt ctacccaagt gaccttcgtg ccccagaatc agaccatcga gagccccgac 600
aacgccctgc agttccggct gtacggcaag gactacaatg tgtacaccca cagctttctg 660
tgctacggaa aggaccaggc tctgtggcag aagctggcca aggacatcca ggtggccagc 720
aacgagatcc tgcgggaccc ttgcttccac cccggctaca agaaagtcgt gaacgtgtcc 780
gacctgtaca agaccccctg caccaagaga ttcgagatga ccctgccctt ccagcagttc 840
gagatccagg gcatcggcaa ttaccagcag tgccaccaga gcatcctgga actgttcaac 900
accagctact gcccctacag ccagtgcgcc ttcaacggca tcttcctgcc acctctgcag 960
ggggatttcg gcgccttcag cgccttctac ttcgtgatga agttcctgaa cctgaccagc 1020
gagaaggtgt cccaggaaaa agtgacagag atgatgaaga agttctgcgc ccagccctgg 1080
gaggaaatca agacctccta cgctggcgtg aaagagaagt acctgagcga gtactgcttc 1140
agcggcacct acatcctgag cctgctgctg cagggctacc acttcaccgc cgatagctgg 1200
gagcacatcc acttcatcgg caagattcag ggcagcgacg ccggctggac actgggctac 1260
atgctgaatc tgaccaacat gatccccgcc gagcagcccc tgagcacacc tctgagccac 1320
agcacc 1326
<210> 68
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 68
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Phe Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu Asp Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 69
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 69
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtttt gcttcagcgg cacctacatc ctgagcctgc tgcagcaggg ctaccacttc 1140
accgccgata gctgggagga catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 70
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 70
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Phe Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 71
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 71
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtttt gcttcagcgg cacctacatc ctgagcctgc tgcagcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 72
<211> 443
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 72
Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Thr Ser Ser Gly
1 5 10 15
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
20 25 30
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
35 40 45
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
50 55 60
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
65 70 75 80
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
85 90 95
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
100 105 110
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
115 120 125
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
130 135 140
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
145 150 155 160
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
165 170 175
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
180 185 190
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
195 200 205
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
210 215 220
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
225 230 235 240
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
245 250 255
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
260 265 270
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
275 280 285
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
290 295 300
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
305 310 315 320
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
325 330 335
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
340 345 350
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
355 360 365
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
370 375 380
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
385 390 395 400
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
405 410 415
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
420 425 430
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
435 440
<210> 73
<211> 1329
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 73
gcccctacct cctccagcac caagaaaacc cagctgacct ccagcggcac ccagaacaag 60
gccctgcccg agaacgtgaa gtacggcatc gtgctggacg ccggctcctc ccacacctcc 120
ctgtacatct acaagtggcc tgccgagaaa gaaaacgaca ccggcgtggt gcaccaagtg 180
gaagagtgca gagtgaaggg ccccggcatc tccaagttcg tgcagaaagt gaacgagatc 240
ggcatctacc tgaccgactg catggaacgg gccagagaag tgatccctcg gtcccagcac 300
caggaaaccc ctgtctacct gggcgccacc gccggcatgc ggctgctgcg gatggaatcc 360
gaggaactgg ccgaccgggt gctggacgtg gtggaacggt ccctgtccaa ctacccattc 420
gattttcaag gcgccagaat catcaccggc caggaagagg gcgcctacgg ctggatcacc 480
atcaactacc tgctgggcaa gttctcccag aagaatcagg aaaccttcgg cgccctggac 540
ctgggcggag ccagcaccca agtcacattc gtgccccaga accagaccat cgagagcccc 600
gacaacgccc tgcagttccg gctgtacggc aaggactaca acgtgtacac ccacagcttt 660
ctgtgctacg gcaaggacca ggccctgtgg cagaagctgg ccaaggacat ccaagtggcc 720
tccaacgaga tcctgcggga cccctgcttc caccccggct acaagaaagt ggtcaacgtg 780
tccgacctgt acaagacccc ttgcaccaag agattcgaga tgaccctgcc cttccagcag 840
ttcgagatcc agggcatcgg caactaccag cagtgccacc agtccatcct ggaactgttc 900
aacacctcct actgccccta ctcccagtgc gccttcaacg gcatcttcct gcctccactg 960
cagggcgact tcggcgcctt ctccgccttc tacttcgtga tgaagttcct gaacctgacc 1020
tccgagaaag tgtcccagga aaaagtgacc gagatgatga agaagttctg cgcccagccc 1080
tgggaggaaa tcaagacctc ctacgctggc gtgaaagaga agtacctgtc cgagtactgc 1140
ttctccggca cctacatcct gtccctgctg ctgcagggct accacttcac cgccgacagc 1200
tgggagcaca tccacttcat cggcaagatc cagggatccg acgctggctg gaccctgggc 1260
tacatgctga atctgaccaa catgatcccc gccgagcagc ccctgtccac ccctctgtct 1320
cactccacc 1329
<210> 74
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 74
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Ser Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 75
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 75
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccatgga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctactccgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgcagcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 76
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 76
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Phe Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 77
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 77
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccatgga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagttct gcttcagcgg cacctacatc ctgagcctgc tgcagcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 78
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 78
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Ser Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 79
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 79
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccatgga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccttgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctactccgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gttacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 80
<211> 433
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 80
Ala Pro Thr Ser Ser Ser Thr Gln Asn Lys Ala Leu Pro Glu Asn Val
1 5 10 15
Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr
20 25 30
Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His
35 40 45
Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val
50 55 60
Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg
65 70 75 80
Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr
85 90 95
Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu
100 105 110
Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr
115 120 125
Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly
130 135 140
Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln
145 150 155 160
Lys Asn Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr
165 170 175
Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn
180 185 190
Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His
195 200 205
Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala
210 215 220
Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe
225 230 235 240
His Pro Gly Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr
245 250 255
Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu
260 265 270
Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu
275 280 285
Leu Phe Asn Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly
290 295 300
Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe
305 310 315 320
Tyr Phe Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln
325 330 335
Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu
340 345 350
Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu
355 360 365
Tyr Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr
370 375 380
His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile
385 390 395 400
Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr
405 410 415
Asn Met Ile Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser
420 425 430
Thr
<210> 81
<211> 1299
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 81
gcccctacca gcagcagcac ccagaacaag gccctgcccg agaacgtgaa gtacggcatc 60
gtgctggatg ccggcagcag ccacaccagc ctgtacatct acaagtggcc tgccgagaaa 120
gaaaacgaca ccggcgtggt gcatcaggtg gaagagtgca gagtgaaggg ccctggcatc 180
agcaagttcg tgcagaaagt gaacgagatc ggcatctacc tgaccgactg catggaacgg 240
gccagggaag tgatccccag aagccagcac caggaaaccc ccgtgtatct gggagccacc 300
gccggcatga gactgctgag aatggaaagc gaggaactgg ccgaccgggt gctggacgtg 360
gtggaaagaa gcctgagcaa ctacccattc gattttcaag gcgccagaat catcaccggc 420
caggaagaag gcgcctacgg ctggatcacc atcaactacc tgctgggcaa gttcagccag 480
aagaatcagg aaaccttcgg cgccctggac ctgggcggag cttctaccca agtgaccttc 540
gtgccccaga atcagaccat cgagagcccc gacaacgccc tgcagttccg gctgtacggc 600
aaggactaca atgtgtacac ccacagcttt ctgtgctacg gaaaggacca ggctctgtgg 660
cagaagctgg ccaaggacat ccaggtggcc agcaacgaga tcctgcggga cccttgcttc 720
caccccggct acaagaaagt cgtgaacgtg tccgacctgt acaagacccc ctgcaccaag 780
agattcgaga tgaccctgcc cttccagcag ttcgagatcc agggcatcgg caattaccag 840
cagtgccacc agagcatcct ggaactgttc aacaccagct actgccccta cagccagtgc 900
gccttcaacg gcatcttcct gccacctctg cagggggatt tcggcgcctt cagcgccttc 960
tacttcgtga tgaagttcct gaacctgacc agcgagaagg tgtcccagga aaaagtgaca 1020
gagatgatga agaagttctg cgcccagccc tgggaggaaa tcaagacctc ctacgctggc 1080
gtgaaagaga agtacctgag cgagtactgc ttcagcggca cctacatcct gagcctgctg 1140
ctgcagggct accacttcac cgccgatagc tgggagcaca tccacttcat cggcaagatt 1200
cagggcagcg acgccggctg gacactgggc tacatgctga atctgaccaa catgatcccc 1260
gccgagcagc ccctgagcac acctctgagc cacagcacc 1299
<210> 82
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 82
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Ala Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 83
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 83
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaagc cggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 84
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 84
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Ala Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ala Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 85
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 85
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaagc cggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agctgctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 86
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 86
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Gln Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Ser Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 87
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 87
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaacagga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctactccgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 88
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 88
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Ala Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Ser Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 89
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 89
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcaggcc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctactccgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 90
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 90
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Gln Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Ser Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 91
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 91
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgcagg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctactccgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 92
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 92
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Gln Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Ser Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 93
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 93
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tccagaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctactccgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 94
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 94
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Ser Val Met Lys Phe
305 310 315 320
Leu Gln Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 95
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 95
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctactccgt gatgaagttc 960
ctgcagctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 96
<211> 427
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 96
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Ser Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr
355 360 365
Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser
370 375 380
Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly
385 390 395 400
Trp Thr Leu Gly Tyr Met Leu Gln Leu Thr Asn Met Ile Pro Ala Glu
405 410 415
Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 97
<211> 1281
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 97
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctactccgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080
agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140
accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200
tggacactgg gctacatgct gcagctgacc aacatgatcc ccgccgagca gcccctgagc 1260
acacctctga gccacagcac c 1281
<210> 98
<211> 69
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 98
tgccctacga gacaaacaat caggaaacct tcggcgccct ggacctgggc ggagcttcta 60
cccaagtga 69
<210> 99
<211> 431
<212> PRT
<213> Homo sapiens
<400> 99
Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu Asp
1 5 10 15
Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala Glu
20 25 30
Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg Val
35 40 45
Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile Gly
50 55 60
Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro Arg
65 70 75 80
Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly Met
85 90 95
Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu Asp
100 105 110
Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly Ala
115 120 125
Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr Ile
130 135 140
Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Thr Arg Trp Phe Ser Ile
145 150 155 160
Val Pro Tyr Glu Thr Asn Asn Gln Glu Thr Phe Gly Ala Leu Asp Leu
165 170 175
Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile
180 185 190
Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr
195 200 205
Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu
210 215 220
Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu
225 230 235 240
Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys Val Val Asn Val Ser
245 250 255
Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro
260 265 270
Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His
275 280 285
Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr Cys Pro Tyr Ser Gln
290 295 300
Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe Gly
305 310 315 320
Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe Leu Asn Leu Thr Ser
325 330 335
Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys
340 345 350
Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu
355 360 365
Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu
370 375 380
Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser Trp Glu His Ile His
385 390 395 400
Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr
405 410 415
Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu Gln Pro Leu Ser
420 425 430
<210> 100
<211> 1293
<212> DNA
<213> Homo sapiens
<400> 100
cagaacaaag ccctgcccga gaacgtgaag tacggcatcg tgctggatgc cggcagcagc 60
cacaccagcc tgtacatcta caagtggcct gccgagaaag aaaacgatac cggtgtcgtg 120
caccaggtgg aagagtgcag agtgaagggc cctggcatca gcaagttcgt gcagaaagtg 180
aacgagatcg gcatctacct gaccgactgc atggaacggg ccagagaagt gatccccaga 240
agccagcacc aggaaacccc cgtgtacctg ggagccacag ccggcatgag actgctgcgg 300
atggaaagcg aggaactggc cgacagagtg ctggacgtgg tggaaagaag cctgagcaac 360
tacccattcg attttcaagg ggccagaatc atcaccggcc aggaagaggg cgcttacggc 420
tggatcacca tcaactacct gctgggcaag ttcagccaga aaacccggtg gttcagcatc 480
gtgccctacg agacaaacaa tcaggaaacc ttcggagccc tggacctggg cggagcctct 540
acccaagtga ccttcgtgcc ccagaatcag accatcgaga gccccgacaa cgccctgcag 600
ttccggctgt acggcaagga ctacaatgtg tacacccaca gctttctgtg ctacggaaag 660
gaccaggccc tgtggcagaa gctggccaag gacatccagg tggccagcaa cgagatcctg 720
cgggaccctt gcttccaccc cggctacaag aaagtcgtga acgtgtccga cctgtacaag 780
accccctgca ccaagagatt cgagatgacc ctgcccttcc agcagttcga gatccagggc 840
atcggcaact accagcagtg ccaccagagc atcctggaac tgttcaacac cagctactgc 900
ccctacagcc agtgcgcctt caacggcatc ttcctgccac ctctgcaggg ggacttcggc 960
gctttcagcg ccttctactt cgtgatgaag ttcctgaacc tgaccagcga gaaggtgtcc 1020
caggaaaaag tgacagagat gatgaagaag ttctgcgccc agccctggga ggaaatcaag 1080
acctcctacg ctggcgtgaa agagaagtac ctgagcgagt actgcttcag cggtacctac 1140
atcctgagcc tgctgctgca gggctaccac ttcaccgccg atagctggga gcacatccac 1200
ttcatcggca agattcaggg cagcgacgcc ggctggacac tgggctacat gctgaatctg 1260
accaacatga tccccgccga gcagcccctg agc 1293
<210> 101
<211> 431
<212> PRT
<213> Homo sapiens
<400> 101
Asn Val Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser
1 5 10 15
Leu Tyr Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val
20 25 30
Val His Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys
35 40 45
Phe Val Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met
50 55 60
Glu Arg Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro
65 70 75 80
Val Tyr Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser
85 90 95
Glu Glu Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser
100 105 110
Asn Tyr Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu
115 120 125
Glu Gly Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe
130 135 140
Ser Gln Lys Thr Arg Trp Phe Ser Ile Val Pro Tyr Glu Thr Asn Asn
145 150 155 160
Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val
165 170 175
Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu
180 185 190
Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe
195 200 205
Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp
210 215 220
Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro
225 230 235 240
Gly Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys
245 250 255
Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln
260 265 270
Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe
275 280 285
Asn Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe
290 295 300
Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe
305 310 315 320
Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys
325 330 335
Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile
340 345 350
Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys
355 360 365
Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe
370 375 380
Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly
385 390 395 400
Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met
405 410 415
Ile Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425 430
<210> 102
<211> 1293
<212> DNA
<213> Homo sapiens
<400> 102
aacgtgaagt acggcatcgt gctggatgcc ggcagcagcc acaccagcct gtacatctac 60
aagtggcctg ccgagaaaga aaacgatacc ggtgtcgtgc accaggtgga agagtgcaga 120
gtgaagggcc ctggcatcag caagttcgtg cagaaagtga acgagatcgg catctacctg 180
accgactgca tggaacgggc cagagaagtg atccccagaa gccagcacca ggaaaccccc 240
gtgtacctgg gagccacagc cggcatgaga ctgctgcgga tggaaagcga ggaactggcc 300
gacagagtgc tggacgtggt ggaaagaagc ctgagcaact acccattcga ttttcaaggg 360
gccagaatca tcaccggcca ggaagagggc gcttacggct ggatcaccat caactacctg 420
ctgggcaagt tcagccagaa aacccggtgg ttcagcatcg tgccctacga gacaaacaat 480
caggaaacct tcggagccct ggacctgggc ggagcctcta cccaagtgac cttcgtgccc 540
cagaatcaga ccatcgagag ccccgacaac gccctgcagt tccggctgta cggcaaggac 600
tacaatgtgt acacccacag ctttctgtgc tacggaaagg accaggccct gtggcagaag 660
ctggccaagg acatccaggt ggccagcaac gagatcctgc gggacccttg cttccacccc 720
ggctacaaga aagtcgtgaa cgtgtccgac ctgtacaaga ccccctgcac caagagattc 780
gagatgaccc tgcccttcca gcagttcgag atccagggca tcggcaacta ccagcagtgc 840
caccagagca tcctggaact gttcaacacc agctactgcc cctacagcca gtgcgccttc 900
aacggcatct tcctgccacc tctgcagggg gacttcggcg ctttcagcgc cttctacttc 960
gtgatgaagt tcctgaacct gaccagcgag aaggtgtccc aggaaaaagt gacagagatg 1020
atgaagaagt tctgcgccca gccctgggag gaaatcaaga cctcctacgc tggcgtgaaa 1080
gagaagtacc tgagcgagta ctgcttcagc ggtacctaca tcctgagcct gctgctgcag 1140
ggctaccact tcaccgccga tagctgggag cacatccact tcatcggcaa gattcagggc 1200
agcgacgccg gctggacact gggctacatg ctgaatctga ccaacatgat ccccgccgag 1260
cagcccctga gcacacctct gtctcacagc acc 1293
<210> 103
<211> 416
<212> PRT
<213> Homo sapiens
<400> 103
Asn Val Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser
1 5 10 15
Leu Tyr Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val
20 25 30
Val His Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys
35 40 45
Phe Val Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met
50 55 60
Glu Arg Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro
65 70 75 80
Val Tyr Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser
85 90 95
Glu Glu Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser
100 105 110
Asn Tyr Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu
115 120 125
Glu Gly Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe
130 135 140
Ser Gln Lys Thr Arg Trp Phe Ser Ile Val Pro Tyr Glu Thr Asn Asn
145 150 155 160
Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val
165 170 175
Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu
180 185 190
Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe
195 200 205
Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp
210 215 220
Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro
225 230 235 240
Gly Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys
245 250 255
Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln
260 265 270
Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe
275 280 285
Asn Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe
290 295 300
Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe
305 310 315 320
Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys
325 330 335
Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile
340 345 350
Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys
355 360 365
Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe
370 375 380
Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly
385 390 395 400
Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met
405 410 415
<210> 104
<211> 1248
<212> DNA
<213> Homo sapiens
<400> 104
aacgtgaagt acggcatcgt gctggatgcc ggcagcagcc acaccagcct gtacatctac 60
aagtggcctg ccgagaaaga aaacgatacc ggtgtcgtgc accaggtgga agagtgcaga 120
gtgaagggcc ctggcatcag caagttcgtg cagaaagtga acgagatcgg catctacctg 180
accgactgca tggaacgggc cagagaagtg atccccagaa gccagcacca ggaaaccccc 240
gtgtacctgg gagccacagc cggcatgaga ctgctgcgga tggaaagcga ggaactggcc 300
gacagagtgc tggacgtggt ggaaagaagc ctgagcaact acccattcga ttttcaaggg 360
gccagaatca tcaccggcca ggaagagggc gcttacggct ggatcaccat caactacctg 420
ctgggcaagt tcagccagaa aacccggtgg ttcagcatcg tgccctacga gacaaacaat 480
caggaaacct tcggagccct ggacctgggc ggagcctcta cccaagtgac cttcgtgccc 540
cagaatcaga ccatcgagag ccccgacaac gccctgcagt tccggctgta cggcaaggac 600
tacaatgtgt acacccacag ctttctgtgc tacggaaagg accaggccct gtggcagaag 660
ctggccaagg acatccaggt ggccagcaac gagatcctgc gggacccttg cttccacccc 720
ggctacaaga aagtcgtgaa cgtgtccgac ctgtacaaga ccccctgcac caagagattc 780
gagatgaccc tgcccttcca gcagttcgag atccagggca tcggcaacta ccagcagtgc 840
caccagagca tcctggaact gttcaacacc agctactgcc cctacagcca gtgcgccttc 900
aacggcatct tcctgccacc tctgcagggg gacttcggcg ctttcagcgc cttctacttc 960
gtgatgaagt tcctgaacct gaccagcgag aaggtgtccc aggaaaaagt gacagagatg 1020
atgaagaagt tctgcgccca gccctgggag gaaatcaaga cctcctacgc tggcgtgaaa 1080
gagaagtacc tgagcgagta ctgcttcagc ggtacctaca tcctgagcct gctgctgcag 1140
ggctaccact tcaccgccga tagctgggag cacatccact tcatcggcaa gattcagggc 1200
agcgacgccg gctggacact gggctacatg ctgaatctga ccaacatg 1248
<210> 105
<211> 404
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 105
Asn Val Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser
1 5 10 15
Leu Tyr Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val
20 25 30
Val His Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys
35 40 45
Phe Val Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met
50 55 60
Glu Arg Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro
65 70 75 80
Val Tyr Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser
85 90 95
Glu Glu Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser
100 105 110
Asn Tyr Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu
115 120 125
Glu Gly Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe
130 135 140
Ser Gln Lys Asn Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala
145 150 155 160
Ser Thr Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro
165 170 175
Asp Asn Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr
180 185 190
Thr His Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys
195 200 205
Leu Ala Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro
210 215 220
Cys Phe His Pro Gly Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr
225 230 235 240
Lys Thr Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln
245 250 255
Phe Glu Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile
260 265 270
Leu Glu Leu Phe Asn Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe
275 280 285
Asn Gly Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser
290 295 300
Ala Phe Tyr Phe Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val
305 310 315 320
Ser Gln Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro
325 330 335
Trp Glu Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu
340 345 350
Ser Glu Tyr Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln
355 360 365
Gly Tyr His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly
370 375 380
Lys Ile Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn
385 390 395 400
Leu Thr Asn Met
<210> 106
<211> 1212
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 106
aacgtgaagt acggcatcgt gctggatgcc ggcagcagcc acaccagcct gtacatctac 60
aagtggcctg ccgagaaaga aaacgatacc ggtgtcgtgc accaggtgga agagtgcaga 120
gtgaagggcc ctggcatcag caagttcgtg cagaaagtga acgagatcgg catctacctg 180
accgactgca tggaacgggc cagagaagtg atccccagaa gccagcacca ggaaaccccc 240
gtgtacctgg gagccacagc cggcatgaga ctgctgcgga tggaaagcga ggaactggcc 300
gacagagtgc tggacgtggt ggaaagaagc ctgagcaact acccattcga ttttcaaggg 360
gccagaatca tcaccggcca ggaagagggc gcttacggct ggatcaccat caactacctg 420
ctgggcaagt tcagccagaa aaatcaggaa accttcggag ccctggacct gggcggagcc 480
tctacccaag tgaccttcgt gccccagaat cagaccatcg agagccccga caacgccctg 540
cagttccggc tgtacggcaa ggactacaat gtgtacaccc acagctttct gtgctacgga 600
aaggaccagg ccctgtggca gaagctggcc aaggacatcc aggtggccag caacgagatc 660
ctgcgggacc cttgcttcca ccccggctac aagaaagtcg tgaacgtgtc cgacctgtac 720
aagaccccct gcaccaagag attcgagatg accctgccct tccagcagtt cgagatccag 780
ggcatcggca actaccagca gtgccaccag agcatcctgg aactgttcaa caccagctac 840
tgcccctaca gccagtgcgc cttcaacggc atcttcctgc cacctctgca gggggacttc 900
ggcgctttca gcgccttcta cttcgtgatg aagttcctga acctgaccag cgagaaggtg 960
tcccaggaaa aagtgacaga gatgatgaag aagttctgcg cccagccctg ggaggaaatc 1020
aagacctcct acgctggcgt gaaagagaag tacctgagcg agtactgctt cagcggtacc 1080
tacatcctga gcctgctgct gcagggctac cacttcaccg ccgatagctg ggagcacatc 1140
cacttcatcg gcaagattca gggcagcgac gccggctgga cactgggcta catgctgaat 1200
ctgaccaaca tg 1212
<210> 107
<211> 416
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 107
Asn Val Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser
1 5 10 15
Leu Tyr Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val
20 25 30
Val His Gln Val Glu Glu Ala Arg Val Lys Gly Pro Gly Ile Ser Lys
35 40 45
Phe Val Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Ala Met
50 55 60
Glu Arg Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro
65 70 75 80
Val Tyr Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser
85 90 95
Glu Glu Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser
100 105 110
Asn Tyr Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu
115 120 125
Glu Gly Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe
130 135 140
Ser Gln Lys Thr Arg Trp Phe Ser Ile Val Pro Tyr Glu Thr Asn Asn
145 150 155 160
Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val
165 170 175
Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu
180 185 190
Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe
195 200 205
Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp
210 215 220
Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro
225 230 235 240
Gly Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys
245 250 255
Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln
260 265 270
Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe
275 280 285
Asn Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe
290 295 300
Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe
305 310 315 320
Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys
325 330 335
Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile
340 345 350
Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys
355 360 365
Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe
370 375 380
Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly
385 390 395 400
Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met
405 410 415
<210> 108
<211> 1248
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 108
aacgtgaagt acggcatcgt gctggatgcc ggcagcagcc acaccagcct gtacatctac 60
aagtggcctg ccgagaaaga aaacgatacc ggtgtcgtgc accaggtgga agaggccaga 120
gtgaagggcc ctggcatcag caagttcgtg cagaaagtga acgagatcgg catctacctg 180
accgacgcca tggaacgggc cagagaagtg atccccagaa gccagcacca ggaaaccccc 240
gtgtacctgg gagccacagc cggcatgaga ctgctgcgga tggaaagcga ggaactggcc 300
gacagagtgc tggacgtggt ggaaagaagc ctgagcaact acccattcga ttttcaaggg 360
gccagaatca tcaccggcca ggaagagggc gcttacggct ggatcaccat caactacctg 420
ctgggcaagt tcagccagaa aacccggtgg ttcagcatcg tgccctacga gacaaacaat 480
caggaaacct tcggagccct ggacctgggc ggagcctcta cccaagtgac cttcgtgccc 540
cagaatcaga ccatcgagag ccccgacaac gccctgcagt tccggctgta cggcaaggac 600
tacaatgtgt acacccacag ctttctgtgc tacggaaagg accaggccct gtggcagaag 660
ctggccaagg acatccaggt ggccagcaac gagatcctgc gggacccttg cttccacccc 720
ggctacaaga aagtcgtgaa cgtgtccgac ctgtacaaga ccccctgcac caagagattc 780
gagatgaccc tgcccttcca gcagttcgag atccagggca tcggcaacta ccagcagtgc 840
caccagagca tcctggaact gttcaacacc agctactgcc cctacagcca gtgcgccttc 900
aacggcatct tcctgccacc tctgcagggg gacttcggcg ctttcagcgc cttctacttc 960
gtgatgaagt tcctgaacct gaccagcgag aaggtgtccc aggaaaaagt gacagagatg 1020
atgaagaagt tctgcgccca gccctgggag gaaatcaaga cctcctacgc tggcgtgaaa 1080
gagaagtacc tgagcgagta ctgcttcagc ggtacctaca tcctgagcct gctgctgcag 1140
ggctaccact tcaccgccga tagctgggag cacatccact tcatcggcaa gattcagggc 1200
agcgacgccg gctggacact gggctacatg ctgaatctga ccaacatg 1248
<210> 109
<211> 416
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 109
Asn Val Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser
1 5 10 15
Leu Tyr Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val
20 25 30
Val His Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys
35 40 45
Phe Val Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met
50 55 60
Glu Arg Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro
65 70 75 80
Val Tyr Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser
85 90 95
Glu Glu Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser
100 105 110
Asn Tyr Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu
115 120 125
Glu Gly Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe
130 135 140
Ser Gln Lys Thr Arg Trp Phe Ser Ile Val Pro Tyr Glu Thr Asn Asn
145 150 155 160
Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val
165 170 175
Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu
180 185 190
Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe
195 200 205
Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp
210 215 220
Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Ala Phe His Pro
225 230 235 240
Gly Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys
245 250 255
Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln
260 265 270
Gly Ile Gly Asn Tyr Gln Gln Ala His Gln Ser Ile Leu Glu Leu Phe
275 280 285
Asn Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe
290 295 300
Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe
305 310 315 320
Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys
325 330 335
Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile
340 345 350
Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys
355 360 365
Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe
370 375 380
Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly
385 390 395 400
Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met
405 410 415
<210> 110
<211> 1248
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 110
aacgtgaagt acggcatcgt gctggatgcc ggcagcagcc acaccagcct gtacatctac 60
aagtggcctg ccgagaaaga aaacgatacc ggtgtcgtgc accaggtgga agagtgcaga 120
gtgaagggcc ctggcatcag caagttcgtg cagaaagtga acgagatcgg catctacctg 180
accgactgca tggaacgggc cagagaagtg atccccagaa gccagcacca ggaaaccccc 240
gtgtacctgg gagccacagc cggcatgaga ctgctgcgga tggaaagcga ggaactggcc 300
gacagagtgc tggacgtggt ggaaagaagc ctgagcaact acccattcga ttttcaaggg 360
gccagaatca tcaccggcca ggaagagggc gcttacggct ggatcaccat caactacctg 420
ctgggcaagt tcagccagaa aacccggtgg ttcagcatcg tgccctacga gacaaacaat 480
caggaaacct tcggagccct ggacctgggc ggagcctcta cccaagtgac cttcgtgccc 540
cagaatcaga ccatcgagag ccccgacaac gccctgcagt tccggctgta cggcaaggac 600
tacaatgtgt acacccacag ctttctgtgc tacggaaagg accaggccct gtggcagaag 660
ctggccaagg acatccaggt ggccagcaac gagatcctgc gggaccctgc cttccacccc 720
ggctacaaga aagtcgtgaa cgtgtccgac ctgtacaaga ccccctgcac caagagattc 780
gagatgaccc tgcccttcca gcagttcgag atccagggca tcggcaacta ccagcaggcc 840
caccagagca tcctggaact gttcaacacc agctactgcc cctacagcca gtgcgccttc 900
aacggcatct tcctgccacc tctgcagggg gacttcggcg ctttcagcgc cttctacttc 960
gtgatgaagt tcctgaacct gaccagcgag aaggtgtccc aggaaaaagt gacagagatg 1020
atgaagaagt tctgcgccca gccctgggag gaaatcaaga cctcctacgc tggcgtgaaa 1080
gagaagtacc tgagcgagta ctgcttcagc ggtacctaca tcctgagcct gctgctgcag 1140
ggctaccact tcaccgccga tagctgggag cacatccact tcatcggcaa gattcagggc 1200
agcgacgccg gctggacact gggctacatg ctgaatctga ccaacatg 1248
<210> 111
<211> 416
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 111
Asn Val Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser
1 5 10 15
Leu Tyr Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val
20 25 30
Val His Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys
35 40 45
Phe Val Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met
50 55 60
Glu Arg Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro
65 70 75 80
Val Tyr Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser
85 90 95
Glu Glu Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser
100 105 110
Asn Tyr Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu
115 120 125
Glu Gly Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe
130 135 140
Ser Gln Lys Thr Arg Trp Phe Ser Ile Val Pro Tyr Glu Thr Asn Asn
145 150 155 160
Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val
165 170 175
Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu
180 185 190
Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe
195 200 205
Leu Ala Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp
210 215 220
Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro
225 230 235 240
Gly Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Ala
245 250 255
Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln
260 265 270
Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe
275 280 285
Asn Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe
290 295 300
Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe
305 310 315 320
Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys
325 330 335
Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile
340 345 350
Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys
355 360 365
Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe
370 375 380
Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly
385 390 395 400
Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met
405 410 415
<210> 112
<211> 1248
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 112
aacgtgaagt acggcatcgt gctggatgcc ggcagcagcc acaccagcct gtacatctac 60
aagtggcctg ccgagaaaga aaacgatacc ggtgtcgtgc accaggtgga agagtgcaga 120
gtgaagggcc ctggcatcag caagttcgtg cagaaagtga acgagatcgg catctacctg 180
accgactgca tggaacgggc cagagaagtg atccccagaa gccagcacca ggaaaccccc 240
gtgtacctgg gagccacagc cggcatgaga ctgctgcgga tggaaagcga ggaactggcc 300
gacagagtgc tggacgtggt ggaaagaagc ctgagcaact acccattcga ttttcaaggg 360
gccagaatca tcaccggcca ggaagagggc gcttacggct ggatcaccat caactacctg 420
ctgggcaagt tcagccagaa aacccggtgg ttcagcatcg tgccctacga gacaaacaat 480
caggaaacct tcggagccct ggacctgggc ggagcctcta cccaagtgac cttcgtgccc 540
cagaatcaga ccatcgagag ccccgacaac gccctgcagt tccggctgta cggcaaggac 600
tacaatgtgt acacccacag ctttctggcc tacggaaagg accaggccct gtggcagaag 660
ctggccaagg acatccaggt ggccagcaac gagatcctgc gggacccttg cttccacccc 720
ggctacaaga aagtcgtgaa cgtgtccgac ctgtacaaga cccccgccac caagagattc 780
gagatgaccc tgcccttcca gcagttcgag atccagggca tcggcaacta ccagcagtgc 840
caccagagca tcctggaact gttcaacacc agctactgcc cctacagcca gtgcgccttc 900
aacggcatct tcctgccacc tctgcagggg gacttcggcg ctttcagcgc cttctacttc 960
gtgatgaagt tcctgaacct gaccagcgag aaggtgtccc aggaaaaagt gacagagatg 1020
atgaagaagt tctgcgccca gccctgggag gaaatcaaga cctcctacgc tggcgtgaaa 1080
gagaagtacc tgagcgagta ctgcttcagc ggtacctaca tcctgagcct gctgctgcag 1140
ggctaccact tcaccgccga tagctgggag cacatccact tcatcggcaa gattcagggc 1200
agcgacgccg gctggacact gggctacatg ctgaatctga ccaacatg 1248
<210> 113
<211> 416
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 113
Asn Val Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser
1 5 10 15
Leu Tyr Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val
20 25 30
Val His Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys
35 40 45
Phe Val Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met
50 55 60
Glu Arg Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro
65 70 75 80
Val Tyr Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser
85 90 95
Glu Glu Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser
100 105 110
Asn Tyr Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu
115 120 125
Glu Gly Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe
130 135 140
Ser Gln Lys Thr Arg Trp Phe Ser Ile Val Pro Tyr Glu Thr Asn Asn
145 150 155 160
Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val
165 170 175
Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu
180 185 190
Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe
195 200 205
Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp
210 215 220
Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro
225 230 235 240
Gly Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys
245 250 255
Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln
260 265 270
Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe
275 280 285
Asn Thr Ser Tyr Ala Pro Tyr Ser Gln Ala Ala Phe Asn Gly Ile Phe
290 295 300
Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe
305 310 315 320
Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys
325 330 335
Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile
340 345 350
Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys
355 360 365
Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe
370 375 380
Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly
385 390 395 400
Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met
405 410 415
<210> 114
<211> 1248
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 114
aacgtgaagt acggcatcgt gctggatgcc ggcagcagcc acaccagcct gtacatctac 60
aagtggcctg ccgagaaaga aaacgatacc ggtgtcgtgc accaggtgga agagtgcaga 120
gtgaagggcc ctggcatcag caagttcgtg cagaaagtga acgagatcgg catctacctg 180
accgactgca tggaacgggc cagagaagtg atccccagaa gccagcacca ggaaaccccc 240
gtgtacctgg gagccacagc cggcatgaga ctgctgcgga tggaaagcga ggaactggcc 300
gacagagtgc tggacgtggt ggaaagaagc ctgagcaact acccattcga ttttcaaggg 360
gccagaatca tcaccggcca ggaagagggc gcttacggct ggatcaccat caactacctg 420
ctgggcaagt tcagccagaa aacccggtgg ttcagcatcg tgccctacga gacaaacaat 480
caggaaacct tcggagccct ggacctgggc ggagcctcta cccaagtgac cttcgtgccc 540
cagaatcaga ccatcgagag ccccgacaac gccctgcagt tccggctgta cggcaaggac 600
tacaatgtgt acacccacag ctttctgtgc tacggaaagg accaggccct gtggcagaag 660
ctggccaagg acatccaggt ggccagcaac gagatcctgc gggacccttg cttccacccc 720
ggctacaaga aagtcgtgaa cgtgtccgac ctgtacaaga ccccctgcac caagagattc 780
gagatgaccc tgcccttcca gcagttcgag atccagggca tcggcaacta ccagcagtgc 840
caccagagca tcctggaact gttcaacacc agctacgccc cctacagcca ggccgccttc 900
aacggcatct tcctgccacc tctgcagggg gacttcggcg ctttcagcgc cttctacttc 960
gtgatgaagt tcctgaacct gaccagcgag aaggtgtccc aggaaaaagt gacagagatg 1020
atgaagaagt tctgcgccca gccctgggag gaaatcaaga cctcctacgc tggcgtgaaa 1080
gagaagtacc tgagcgagta ctgcttcagc ggtacctaca tcctgagcct gctgctgcag 1140
ggctaccact tcaccgccga tagctgggag cacatccact tcatcggcaa gattcagggc 1200
agcgacgccg gctggacact gggctacatg ctgaatctga ccaacatg 1248
<210> 115
<211> 416
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 115
Asn Val Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser
1 5 10 15
Leu Tyr Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val
20 25 30
Val His Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys
35 40 45
Phe Val Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met
50 55 60
Glu Arg Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro
65 70 75 80
Val Tyr Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser
85 90 95
Glu Glu Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser
100 105 110
Asn Tyr Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu
115 120 125
Glu Gly Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe
130 135 140
Ser Gln Lys Thr Arg Trp Phe Ser Ile Val Pro Tyr Glu Thr Asn Asn
145 150 155 160
Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val
165 170 175
Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu
180 185 190
Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe
195 200 205
Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp
210 215 220
Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro
225 230 235 240
Gly Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys
245 250 255
Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln
260 265 270
Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe
275 280 285
Asn Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe
290 295 300
Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe
305 310 315 320
Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys
325 330 335
Val Thr Glu Met Met Lys Lys Phe Ala Ala Gln Pro Trp Glu Glu Ile
340 345 350
Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Ala
355 360 365
Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe
370 375 380
Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly
385 390 395 400
Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met
405 410 415
<210> 116
<211> 1248
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 116
aacgtgaagt acggcatcgt gctggatgcc ggcagcagcc acaccagcct gtacatctac 60
aagtggcctg ccgagaaaga aaacgatacc ggtgtcgtgc accaggtgga agagtgcaga 120
gtgaagggcc ctggcatcag caagttcgtg cagaaagtga acgagatcgg catctacctg 180
accgactgca tggaacgggc cagagaagtg atccccagaa gccagcacca ggaaaccccc 240
gtgtacctgg gagccacagc cggcatgaga ctgctgcgga tggaaagcga ggaactggcc 300
gacagagtgc tggacgtggt ggaaagaagc ctgagcaact acccattcga ttttcaaggg 360
gccagaatca tcaccggcca ggaagagggc gcttacggct ggatcaccat caactacctg 420
ctgggcaagt tcagccagaa aacccggtgg ttcagcatcg tgccctacga gacaaacaat 480
caggaaacct tcggagccct ggacctgggc ggagcctcta cccaagtgac cttcgtgccc 540
cagaatcaga ccatcgagag ccccgacaac gccctgcagt tccggctgta cggcaaggac 600
tacaatgtgt acacccacag ctttctgtgc tacggaaagg accaggccct gtggcagaag 660
ctggccaagg acatccaggt ggccagcaac gagatcctgc gggacccttg cttccacccc 720
ggctacaaga aagtcgtgaa cgtgtccgac ctgtacaaga ccccctgcac caagagattc 780
gagatgaccc tgcccttcca gcagttcgag atccagggca tcggcaacta ccagcagtgc 840
caccagagca tcctggaact gttcaacacc agctactgcc cctacagcca gtgcgccttc 900
aacggcatct tcctgccacc tctgcagggg gacttcggcg ctttcagcgc cttctacttc 960
gtgatgaagt tcctgaacct gaccagcgag aaggtgtccc aggaaaaagt gacagagatg 1020
atgaagaagt tcgccgccca gccctgggag gaaatcaaga cctcctacgc tggcgtgaaa 1080
gagaagtacc tgagcgagta cgccttcagc ggtacctaca tcctgagcct gctgctgcag 1140
ggctaccact tcaccgccga tagctgggag cacatccact tcatcggcaa gattcagggc 1200
agcgacgccg gctggacact gggctacatg ctgaatctga ccaacatg 1248
<210> 117
<211> 404
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 117
Asn Val Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser
1 5 10 15
Leu Tyr Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val
20 25 30
Val His Gln Val Glu Glu Ala Arg Val Lys Gly Pro Gly Ile Ser Lys
35 40 45
Phe Val Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Ala Met
50 55 60
Glu Arg Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro
65 70 75 80
Val Tyr Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser
85 90 95
Glu Glu Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser
100 105 110
Asn Tyr Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu
115 120 125
Glu Gly Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe
130 135 140
Ser Gln Lys Asn Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala
145 150 155 160
Ser Thr Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro
165 170 175
Asp Asn Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr
180 185 190
Thr His Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys
195 200 205
Leu Ala Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro
210 215 220
Cys Phe His Pro Gly Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr
225 230 235 240
Lys Thr Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln
245 250 255
Phe Glu Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile
260 265 270
Leu Glu Leu Phe Asn Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe
275 280 285
Asn Gly Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser
290 295 300
Ala Phe Tyr Phe Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val
305 310 315 320
Ser Gln Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro
325 330 335
Trp Glu Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu
340 345 350
Ser Glu Tyr Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln
355 360 365
Gly Tyr His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly
370 375 380
Lys Ile Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn
385 390 395 400
Leu Thr Asn Met
<210> 118
<211> 1212
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 118
aacgtgaagt acggcatcgt gctggatgcc ggcagcagcc acaccagcct gtacatctac 60
aagtggcctg ccgagaaaga aaacgatacc ggtgtcgtgc accaggtgga agaggccaga 120
gtgaagggcc ctggcatcag caagttcgtg cagaaagtga acgagatcgg catctacctg 180
accgacgcca tggaacgggc cagagaagtg atccccagaa gccagcacca ggaaaccccc 240
gtgtacctgg gagccacagc cggcatgaga ctgctgcgga tggaaagcga ggaactggcc 300
gacagagtgc tggacgtggt ggaaagaagc ctgagcaact acccattcga ttttcaaggg 360
gccagaatca tcaccggcca ggaagagggc gcttacggct ggatcaccat caactacctg 420
ctgggcaagt tcagccagaa aaatcaggaa accttcggag ccctggacct gggcggagcc 480
tctacccaag tgaccttcgt gccccagaat cagaccatcg agagccccga caacgccctg 540
cagttccggc tgtacggcaa ggactacaat gtgtacaccc acagctttct gtgctacgga 600
aaggaccagg ccctgtggca gaagctggcc aaggacatcc aggtggccag caacgagatc 660
ctgcgggacc cttgcttcca ccccggctac aagaaagtcg tgaacgtgtc cgacctgtac 720
aagaccccct gcaccaagag attcgagatg accctgccct tccagcagtt cgagatccag 780
ggcatcggca actaccagca gtgccaccag agcatcctgg aactgttcaa caccagctac 840
tgcccctaca gccagtgcgc cttcaacggc atcttcctgc cacctctgca gggggacttc 900
ggcgctttca gcgccttcta cttcgtgatg aagttcctga acctgaccag cgagaaggtg 960
tcccaggaaa aagtgacaga gatgatgaag aagttctgcg cccagccctg ggaggaaatc 1020
aagacctcct acgctggcgt gaaagagaag tacctgagcg agtactgctt cagcggtacc 1080
tacatcctga gcctgctgct gcagggctac cacttcaccg ccgatagctg ggagcacatc 1140
cacttcatcg gcaagattca gggcagcgac gccggctgga cactgggcta catgctgaat 1200
ctgaccaaca tg 1212
<210> 119
<211> 404
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 119
Asn Val Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser
1 5 10 15
Leu Tyr Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val
20 25 30
Val His Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys
35 40 45
Phe Val Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met
50 55 60
Glu Arg Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro
65 70 75 80
Val Tyr Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser
85 90 95
Glu Glu Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser
100 105 110
Asn Tyr Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu
115 120 125
Glu Gly Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe
130 135 140
Ser Gln Lys Asn Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala
145 150 155 160
Ser Thr Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro
165 170 175
Asp Asn Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr
180 185 190
Thr His Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys
195 200 205
Leu Ala Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro
210 215 220
Ala Phe His Pro Gly Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr
225 230 235 240
Lys Thr Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln
245 250 255
Phe Glu Ile Gln Gly Ile Gly Asn Tyr Gln Gln Ala His Gln Ser Ile
260 265 270
Leu Glu Leu Phe Asn Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe
275 280 285
Asn Gly Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser
290 295 300
Ala Phe Tyr Phe Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val
305 310 315 320
Ser Gln Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro
325 330 335
Trp Glu Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu
340 345 350
Ser Glu Tyr Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln
355 360 365
Gly Tyr His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly
370 375 380
Lys Ile Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn
385 390 395 400
Leu Thr Asn Met
<210> 120
<211> 1212
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 120
aacgtgaagt acggcatcgt gctggatgcc ggcagcagcc acaccagcct gtacatctac 60
aagtggcctg ccgagaaaga aaacgatacc ggtgtcgtgc accaggtgga agagtgcaga 120
gtgaagggcc ctggcatcag caagttcgtg cagaaagtga acgagatcgg catctacctg 180
accgactgca tggaacgggc cagagaagtg atccccagaa gccagcacca ggaaaccccc 240
gtgtacctgg gagccacagc cggcatgaga ctgctgcgga tggaaagcga ggaactggcc 300
gacagagtgc tggacgtggt ggaaagaagc ctgagcaact acccattcga ttttcaaggg 360
gccagaatca tcaccggcca ggaagagggc gcttacggct ggatcaccat caactacctg 420
ctgggcaagt tcagccagaa aaatcaggaa accttcggag ccctggacct gggcggagcc 480
tctacccaag tgaccttcgt gccccagaat cagaccatcg agagccccga caacgccctg 540
cagttccggc tgtacggcaa ggactacaat gtgtacaccc acagctttct gtgctacgga 600
aaggaccagg ccctgtggca gaagctggcc aaggacatcc aggtggccag caacgagatc 660
ctgcgggacc ctgccttcca ccccggctac aagaaagtcg tgaacgtgtc cgacctgtac 720
aagaccccct gcaccaagag attcgagatg accctgccct tccagcagtt cgagatccag 780
ggcatcggca actaccagca ggcccaccag agcatcctgg aactgttcaa caccagctac 840
tgcccctaca gccagtgcgc cttcaacggc atcttcctgc cacctctgca gggggacttc 900
ggcgctttca gcgccttcta cttcgtgatg aagttcctga acctgaccag cgagaaggtg 960
tcccaggaaa aagtgacaga gatgatgaag aagttctgcg cccagccctg ggaggaaatc 1020
aagacctcct acgctggcgt gaaagagaag tacctgagcg agtactgctt cagcggtacc 1080
tacatcctga gcctgctgct gcagggctac cacttcaccg ccgatagctg ggagcacatc 1140
cacttcatcg gcaagattca gggcagcgac gccggctgga cactgggcta catgctgaat 1200
ctgaccaaca tg 1212
<210> 121
<211> 404
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 121
Asn Val Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser
1 5 10 15
Leu Tyr Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val
20 25 30
Val His Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys
35 40 45
Phe Val Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met
50 55 60
Glu Arg Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro
65 70 75 80
Val Tyr Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser
85 90 95
Glu Glu Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser
100 105 110
Asn Tyr Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu
115 120 125
Glu Gly Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe
130 135 140
Ser Gln Lys Asn Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala
145 150 155 160
Ser Thr Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro
165 170 175
Asp Asn Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr
180 185 190
Thr His Ser Phe Leu Ala Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys
195 200 205
Leu Ala Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro
210 215 220
Cys Phe His Pro Gly Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr
225 230 235 240
Lys Thr Pro Ala Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln
245 250 255
Phe Glu Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile
260 265 270
Leu Glu Leu Phe Asn Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe
275 280 285
Asn Gly Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser
290 295 300
Ala Phe Tyr Phe Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val
305 310 315 320
Ser Gln Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro
325 330 335
Trp Glu Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu
340 345 350
Ser Glu Tyr Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln
355 360 365
Gly Tyr His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly
370 375 380
Lys Ile Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn
385 390 395 400
Leu Thr Asn Met
<210> 122
<211> 1212
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 122
aacgtgaagt acggcatcgt gctggatgcc ggcagcagcc acaccagcct gtacatctac 60
aagtggcctg ccgagaaaga aaacgatacc ggtgtcgtgc accaggtgga agagtgcaga 120
gtgaagggcc ctggcatcag caagttcgtg cagaaagtga acgagatcgg catctacctg 180
accgactgca tggaacgggc cagagaagtg atccccagaa gccagcacca ggaaaccccc 240
gtgtacctgg gagccacagc cggcatgaga ctgctgcgga tggaaagcga ggaactggcc 300
gacagagtgc tggacgtggt ggaaagaagc ctgagcaact acccattcga ttttcaaggg 360
gccagaatca tcaccggcca ggaagagggc gcttacggct ggatcaccat caactacctg 420
ctgggcaagt tcagccagaa aaatcaggaa accttcggag ccctggacct gggcggagcc 480
tctacccaag tgaccttcgt gccccagaat cagaccatcg agagccccga caacgccctg 540
cagttccggc tgtacggcaa ggactacaat gtgtacaccc acagctttct ggcctacgga 600
aaggaccagg ccctgtggca gaagctggcc aaggacatcc aggtggccag caacgagatc 660
ctgcgggacc cttgcttcca ccccggctac aagaaagtcg tgaacgtgtc cgacctgtac 720
aagacccccg ccaccaagag attcgagatg accctgccct tccagcagtt cgagatccag 780
ggcatcggca actaccagca gtgccaccag agcatcctgg aactgttcaa caccagctac 840
tgcccctaca gccagtgcgc cttcaacggc atcttcctgc cacctctgca gggggacttc 900
ggcgctttca gcgccttcta cttcgtgatg aagttcctga acctgaccag cgagaaggtg 960
tcccaggaaa aagtgacaga gatgatgaag aagttctgcg cccagccctg ggaggaaatc 1020
aagacctcct acgctggcgt gaaagagaag tacctgagcg agtactgctt cagcggtacc 1080
tacatcctga gcctgctgct gcagggctac cacttcaccg ccgatagctg ggagcacatc 1140
cacttcatcg gcaagattca gggcagcgac gccggctgga cactgggcta catgctgaat 1200
ctgaccaaca tg 1212
<210> 123
<211> 404
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 123
Asn Val Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser
1 5 10 15
Leu Tyr Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val
20 25 30
Val His Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys
35 40 45
Phe Val Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met
50 55 60
Glu Arg Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro
65 70 75 80
Val Tyr Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser
85 90 95
Glu Glu Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser
100 105 110
Asn Tyr Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu
115 120 125
Glu Gly Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe
130 135 140
Ser Gln Lys Asn Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala
145 150 155 160
Ser Thr Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro
165 170 175
Asp Asn Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr
180 185 190
Thr His Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys
195 200 205
Leu Ala Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro
210 215 220
Cys Phe His Pro Gly Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr
225 230 235 240
Lys Thr Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln
245 250 255
Phe Glu Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile
260 265 270
Leu Glu Leu Phe Asn Thr Ser Tyr Ala Pro Tyr Ser Gln Ala Ala Phe
275 280 285
Asn Gly Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser
290 295 300
Ala Phe Tyr Phe Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val
305 310 315 320
Ser Gln Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro
325 330 335
Trp Glu Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu
340 345 350
Ser Glu Tyr Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln
355 360 365
Gly Tyr His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly
370 375 380
Lys Ile Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn
385 390 395 400
Leu Thr Asn Met
<210> 124
<211> 1212
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 124
aacgtgaagt acggcatcgt gctggatgcc ggcagcagcc acaccagcct gtacatctac 60
aagtggcctg ccgagaaaga aaacgatacc ggtgtcgtgc accaggtgga agagtgcaga 120
gtgaagggcc ctggcatcag caagttcgtg cagaaagtga acgagatcgg catctacctg 180
accgactgca tggaacgggc cagagaagtg atccccagaa gccagcacca ggaaaccccc 240
gtgtacctgg gagccacagc cggcatgaga ctgctgcgga tggaaagcga ggaactggcc 300
gacagagtgc tggacgtggt ggaaagaagc ctgagcaact acccattcga ttttcaaggg 360
gccagaatca tcaccggcca ggaagagggc gcttacggct ggatcaccat caactacctg 420
ctgggcaagt tcagccagaa aaatcaggaa accttcggag ccctggacct gggcggagcc 480
tctacccaag tgaccttcgt gccccagaat cagaccatcg agagccccga caacgccctg 540
cagttccggc tgtacggcaa ggactacaat gtgtacaccc acagctttct gtgctacgga 600
aaggaccagg ccctgtggca gaagctggcc aaggacatcc aggtggccag caacgagatc 660
ctgcgggacc cttgcttcca ccccggctac aagaaagtcg tgaacgtgtc cgacctgtac 720
aagaccccct gcaccaagag attcgagatg accctgccct tccagcagtt cgagatccag 780
ggcatcggca actaccagca gtgccaccag agcatcctgg aactgttcaa caccagctac 840
gccccctaca gccaggccgc cttcaacggc atcttcctgc cacctctgca gggggacttc 900
ggcgctttca gcgccttcta cttcgtgatg aagttcctga acctgaccag cgagaaggtg 960
tcccaggaaa aagtgacaga gatgatgaag aagttctgcg cccagccctg ggaggaaatc 1020
aagacctcct acgctggcgt gaaagagaag tacctgagcg agtactgctt cagcggtacc 1080
tacatcctga gcctgctgct gcagggctac cacttcaccg ccgatagctg ggagcacatc 1140
cacttcatcg gcaagattca gggcagcgac gccggctgga cactgggcta catgctgaat 1200
ctgaccaaca tg 1212
<210> 125
<211> 404
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 125
Asn Val Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser
1 5 10 15
Leu Tyr Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val
20 25 30
Val His Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys
35 40 45
Phe Val Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met
50 55 60
Glu Arg Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro
65 70 75 80
Val Tyr Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser
85 90 95
Glu Glu Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser
100 105 110
Asn Tyr Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu
115 120 125
Glu Gly Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe
130 135 140
Ser Gln Lys Asn Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala
145 150 155 160
Ser Thr Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro
165 170 175
Asp Asn Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr
180 185 190
Thr His Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys
195 200 205
Leu Ala Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro
210 215 220
Cys Phe His Pro Gly Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr
225 230 235 240
Lys Thr Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln
245 250 255
Phe Glu Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile
260 265 270
Leu Glu Leu Phe Asn Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe
275 280 285
Asn Gly Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser
290 295 300
Ala Phe Tyr Phe Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val
305 310 315 320
Ser Gln Glu Lys Val Thr Glu Met Met Lys Lys Phe Ala Ala Gln Pro
325 330 335
Trp Glu Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu
340 345 350
Ser Glu Tyr Ala Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln
355 360 365
Gly Tyr His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly
370 375 380
Lys Ile Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn
385 390 395 400
Leu Thr Asn Met
<210> 126
<211> 1212
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 126
aacgtgaagt acggcatcgt gctggatgcc ggcagcagcc acaccagcct gtacatctac 60
aagtggcctg ccgagaaaga aaacgatacc ggtgtcgtgc accaggtgga agagtgcaga 120
gtgaagggcc ctggcatcag caagttcgtg cagaaagtga acgagatcgg catctacctg 180
accgactgca tggaacgggc cagagaagtg atccccagaa gccagcacca ggaaaccccc 240
gtgtacctgg gagccacagc cggcatgaga ctgctgcgga tggaaagcga ggaactggcc 300
gacagagtgc tggacgtggt ggaaagaagc ctgagcaact acccattcga ttttcaaggg 360
gccagaatca tcaccggcca ggaagagggc gcttacggct ggatcaccat caactacctg 420
ctgggcaagt tcagccagaa aaatcaggaa accttcggag ccctggacct gggcggagcc 480
tctacccaag tgaccttcgt gccccagaat cagaccatcg agagccccga caacgccctg 540
cagttccggc tgtacggcaa ggactacaat gtgtacaccc acagctttct gtgctacgga 600
aaggaccagg ccctgtggca gaagctggcc aaggacatcc aggtggccag caacgagatc 660
ctgcgggacc cttgcttcca ccccggctac aagaaagtcg tgaacgtgtc cgacctgtac 720
aagaccccct gcaccaagag attcgagatg accctgccct tccagcagtt cgagatccag 780
ggcatcggca actaccagca gtgccaccag agcatcctgg aactgttcaa caccagctac 840
tgcccctaca gccagtgcgc cttcaacggc atcttcctgc cacctctgca gggggacttc 900
ggcgctttca gcgccttcta cttcgtgatg aagttcctga acctgaccag cgagaaggtg 960
tcccaggaaa aagtgacaga gatgatgaag aagttcgccg cccagccctg ggaggaaatc 1020
aagacctcct acgctggcgt gaaagagaag tacctgagcg agtacgcctt cagcggtacc 1080
tacatcctga gcctgctgct gcagggctac cacttcaccg ccgatagctg ggagcacatc 1140
cacttcatcg gcaagattca gggcagcgac gccggctgga cactgggcta catgctgaat 1200
ctgaccaaca tg 1212
<210> 127
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 127
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Thr Arg Trp Phe Ser
145 150 155 160
Ile Val Pro Tyr Glu Thr Asn Asn Gln Glu Thr Phe Gly Ala Leu Asp
165 170 175
Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro Gln Asn Gln Thr
180 185 190
Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp
195 200 205
Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala
210 215 220
Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala Ser Asn Glu Ile
225 230 235 240
Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys Val Val Asn Val
245 250 255
Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe Glu Met Thr Leu
260 265 270
Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys
275 280 285
His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Phe Asn Gly Ile Phe
290 295 300
Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe
305 310 315 320
Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys
325 330 335
Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile
340 345 350
Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys
355 360 365
Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe
370 375 380
Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly
385 390 395 400
Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met
405 410 415
Ile Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425 430
<210> 128
<211> 1293
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 128
acacagaaca aagccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga taccggtgtc 120
gtgcaccagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccagaga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtac ctgggagcca cagccggcat gagactgctg 300
cggatggaaa gcgaggaact ggccgacaga gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggggccaga atcatcaccg gccaggaaga gggcgcttac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaaaacccg gtggttcagc 480
atcgtgccct acgagacaaa caatcaggaa accttcggag ccctggacct gggcggagcc 540
tctacccaag tgaccttcgt gccccagaat cagaccatcg agagccccga caacgccctg 600
cagttccggc tgtacggcaa ggactacaat gtgtacaccc acagctttct gtgctacgga 660
aaggaccagg ccctgtggca gaagctggcc aaggacatcc aggtggccag caacgagatc 720
ctgcgggacc cttgcttcca ccccggctac aagaaagtcg tgaacgtgtc cgacctgtac 780
aagaccccct gcaccaagag attcgagatg accctgccct tccagcagtt cgagatccag 840
ggcatcggca actaccagca gtgccaccag agcatcctgg aactgttcaa caccagcttc 900
aacggcatct tcctgccacc tctgcagggg gacttcggcg ctttcagcgc cttctacttc 960
gtgatgaagt tcctgaacct gaccagcgag aaggtgtccc aggaaaaagt gacagagatg 1020
atgaagaagt tctgcgccca gccctgggag gaaatcaaga cctcctacgc tggcgtgaaa 1080
gagaagtacc tgagcgagta ctgcttcagc ggtacctaca tcctgagcct gctgctgcag 1140
ggctaccact tcaccgccga tagctgggag cacatccact tcatcggcaa gattcagggc 1200
agcgacgccg gctggacact gggctacatg ctgaatctga ccaacatgat ccccgccgag 1260
cagcccctga gcacacctct gtctcacagc acc 1293
<210> 129
<211> 439
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 129
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Thr Arg Trp Phe Ser
145 150 155 160
Ile Val Pro Tyr Glu Thr Asn Asn Gln Glu Thr Phe Gly Ala Leu Asp
165 170 175
Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro Gln Asn Gln Thr
180 185 190
Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp
195 200 205
Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala
210 215 220
Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala Ser Asn Glu Ile
225 230 235 240
Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys Val Val Asn Val
245 250 255
Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe Glu Met Thr Leu
260 265 270
Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys
275 280 285
His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr Ala Pro Tyr Ser
290 295 300
Gln Ala Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe
305 310 315 320
Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe Leu Asn Leu Thr
325 330 335
Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met Met Lys Lys Phe
340 345 350
Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys
355 360 365
Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr Tyr Ile Leu Ser
370 375 380
Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser Trp Glu His Ile
385 390 395 400
His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly
405 410 415
Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu Gln Pro Leu Ser
420 425 430
Thr Pro Leu Ser His Ser Thr
435
<210> 130
<211> 1317
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 130
acacagaaca aagccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga taccggtgtc 120
gtgcaccagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccagaga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtac ctgggagcca cagccggcat gagactgctg 300
cggatggaaa gcgaggaact ggccgacaga gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggggccaga atcatcaccg gccaggaaga gggcgcttac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaaaacccg gtggttcagc 480
atcgtgccct acgagacaaa caatcaggaa accttcggag ccctggacct gggcggagcc 540
tctacccaag tgaccttcgt gccccagaat cagaccatcg agagccccga caacgccctg 600
cagttccggc tgtacggcaa ggactacaat gtgtacaccc acagctttct gtgctacgga 660
aaggaccagg ccctgtggca gaagctggcc aaggacatcc aggtggccag caacgagatc 720
ctgcgggacc cttgcttcca ccccggctac aagaaagtcg tgaacgtgtc cgacctgtac 780
aagaccccct gcaccaagag attcgagatg accctgccct tccagcagtt cgagatccag 840
ggcatcggca actaccagca gtgccaccag agcatcctgg aactgttcaa caccagctac 900
gccccctaca gccaggccgc cttcaacggc atcttcctgc cacctctgca gggggacttc 960
ggcgctttca gcgccttcta cttcgtgatg aagttcctga acctgaccag cgagaaggtg 1020
tcccaggaaa aagtgacaga gatgatgaag aagttctgcg cccagccctg ggaggaaatc 1080
aagacctcct acgctggcgt gaaagagaag tacctgagcg agtactgctt cagcggtacc 1140
tacatcctga gcctgctgct gcagggctac cacttcaccg ccgatagctg ggagcacatc 1200
cacttcatcg gcaagattca gggcagcgac gccggctgga cactgggcta catgctgaat 1260
ctgaccaaca tgatccccgc cgagcagccc ctgagcacac ctctgtctca cagcacc 1317
<210> 131
<211> 16
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 131
Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Thr Ser Ser Gly
1 5 10 15
<210> 132
<211> 48
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 132
gcccccacca gcagcagcac caagaagacc cagctgacca gcagcggc 48
<210> 133
<211> 15
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 133
Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Thr Ser Ser
1 5 10 15
<210> 134
<211> 45
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 134
gcccctacca gcagcagcac caagaaaacc cagctgacca gcagc 45
<210> 135
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 135
Ala Pro Thr Ser Ser Ser
1 5
<210> 136
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 136
gcccctacca gcagcagc 18
<210> 137
<211> 3
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 137
Ala Pro Thr
1
<210> 138
<211> 9
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 138
gcccctacc 9
<210> 139
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 139
Ala Pro Thr Ser Ser Ser Thr Lys Lys
1 5
<210> 140
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 140
gcccctacca gcagcagcac caagaaa 27
<210> 141
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 141
Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu
1 5 10
<210> 142
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 142
gcccctacca gcagcagcac caagaaaacc cagctg 36
<210> 143
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 143
Ser Ser Ser Thr Lys Lys Thr Gln Leu
1 5
<210> 144
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 144
agcagcagca ccaagaaaac ccagctg 27
<210> 145
<211> 426
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 145
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Asp Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe
145 150 155 160
Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro
165 170 175
Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu
180 185 190
Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly
195 200 205
Arg Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala
210 215 220
Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys
225 230 235 240
Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe
245 250 255
Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn
260 265 270
Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr
275 280 285
Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu
290 295 300
Gln Gly Asp Phe Gly Ala Phe Ser Asn Phe Tyr Tyr Val Met Lys Phe
305 310 315 320
Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met
325 330 335
Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr
340 345 350
Ala Gly Gln Glu Arg Trp Leu Arg Asp Tyr Cys Phe Ser Gly Thr Tyr
355 360 365
Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser Trp
370 375 380
Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly Trp
385 390 395 400
Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu Gln
405 410 415
Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425
<210> 146
<211> 1278
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 146
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccagaga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggacga gggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480
ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540
atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600
acccacagct ttctgtgcta cggccgggac caggctctgt ggcagaagct ggccaaggac 660
atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720
gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780
cccttccagc agttcgagat ccagggcatc ggcaactacc agcagtgcca ccagagcatc 840
ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900
ctgccacctc tgcaggggga tttcggcgcc ttcagcaact tctactacgt gatgaagttc 960
ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020
tgcgcccagc cctgggagga aatcaagacc tcttacgccg gacaggaacg gtggctgcgg 1080
gactactgtt tcagcggcac ctacatcctg tccctgctgc tgcagggcta ccacttcacc 1140
gccgatagct gggagcacat ccacttcatc ggcaagattc agggcagcga cgccggctgg 1200
acactgggct acatgctgaa tctgaccaac atgatccccg ccgagcagcc cctgagcaca 1260
cctctgtctc acagcacc 1278
<210> 147
<211> 537
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 147
Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln
1 5 10 15
Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr
20 25 30
Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser
35 40 45
Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr
50 55 60
Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys
65 70 75 80
His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro
85 90 95
Val Thr Lys Ser Phe Asn Arg Gly Glu Gly Gly Gly Gly Ser Thr Gln
100 105 110
Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu Asp Ala
115 120 125
Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala Glu Lys
130 135 140
Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg Val Lys
145 150 155 160
Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile Gly Ile
165 170 175
Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro Arg Ser
180 185 190
Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly Met Arg
195 200 205
Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu Asp Val
210 215 220
Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly Ala Arg
225 230 235 240
Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr Ile Asn
245 250 255
Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe Gly Ala
260 265 270
Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro Gln Asn
275 280 285
Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu Tyr Gly
290 295 300
Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly Lys Asp
305 310 315 320
Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala Ser Asn
325 330 335
Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys Val Val
340 345 350
Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe Glu Met
355 360 365
Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn Tyr Gln
370 375 380
Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr Cys Pro
385 390 395 400
Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu Gln Gly
405 410 415
Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe Leu Asn
420 425 430
Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met Met Lys
435 440 445
Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr Ala Gly
450 455 460
Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr Tyr Ile
465 470 475 480
Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser Trp Glu
485 490 495
His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly Trp Thr
500 505 510
Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu Gln Pro
515 520 525
Leu Ser Thr Pro Leu Ser His Ser Thr
530 535
<210> 148
<211> 1611
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 148
acggtggccg ctcccagcgt gttcatcttc ccccccagcg acgagcagct gaagagcggc 60
accgccagcg tggtgtgcct gctgaacaac ttctaccccc gggaggccaa ggtgcagtgg 120
aaggtggaca acgccctgca gagcggcaac agccaggaaa gcgtcaccga gcaggacagc 180
aaggactcca cctacagcct gagcagcacc ctgaccctga gcaaggccga ctacgagaag 240
cacaaggtgt acgcctgcga ggtgacccac cagggcctgt ccagccccgt gaccaagagc 300
ttcaaccggg gcgagggagg cggaggatct acccagaaca aggccctgcc cgagaacgtg 360
aagtacggca tcgtgctgga tgccggcagc agccacacca gcctgtacat ctacaagtgg 420
cctgccgaga aagaaaacga caccggcgtg gtgcatcagg tggaagagtg cagagtgaag 480
ggccctggca tcagcaagtt cgtgcagaaa gtgaacgaga tcggcatcta cctgaccgac 540
tgcatggaac gggccaggga agtgatcccc agaagccagc accaggaaac ccccgtgtat 600
ctgggagcca ccgccggcat gagactgctg agaatggaaa gcgaggaact ggccgaccgg 660
gtgctggacg tggtggaaag aagcctgagc aactacccat tcgattttca aggcgccaga 720
atcatcaccg gccaggaaga aggcgcctac ggctggatca ccatcaacta cctgctgggc 780
aagttcagcc agaagaatca ggaaaccttc ggcgccctgg acctgggcgg agcttctacc 840
caagtgacct tcgtgcccca gaatcagacc atcgagagcc ccgacaacgc cctgcagttc 900
cggctgtacg gcaaggacta caatgtgtac acccacagct ttctgtgcta cggaaaggac 960
caggctctgt ggcagaagct ggccaaggac atccaggtgg ccagcaacga gatcctgcgg 1020
gacccttgct tccaccccgg ctacaagaaa gtcgtgaacg tgtccgacct gtacaagacc 1080
ccctgcacca agagattcga gatgaccctg cccttccagc agttcgagat ccagggcatc 1140
ggcaattacc agcagtgcca ccagagcatc ctggaactgt tcaacaccag ctactgcccc 1200
tacagccagt gcgccttcaa cggcatcttc ctgccacctc tgcaggggga tttcggcgcc 1260
ttcagcgcct tctacttcgt gatgaagttc ctgaacctga ccagcgagaa ggtgtcccag 1320
gaaaaagtga cagagatgat gaagaagttc tgcgcccagc cctgggagga aatcaagacc 1380
tcctacgctg gcgtgaaaga gaagtacctg agcgagtact gcttcagcgg cacctacatc 1440
ctgagcctgc tgctgcaggg ctaccacttc accgccgata gctgggagca catccacttc 1500
atcggcaaga ttcagggcag cgacgccggc tggacactgg gctacatgct gaatctgacc 1560
aacatgatcc ccgccgagca gcccctgagc acacctctga gccacagcac c 1611
<210> 149
<211> 508
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 149
Met Gln Ile Phe Val Lys Thr Leu Thr Gly Lys Thr Ile Thr Leu Glu
1 5 10 15
Val Glu Pro Ser Asp Thr Ile Glu Asn Val Lys Ala Lys Ile Gln Asp
20 25 30
Lys Glu Gly Ile Pro Pro Asp Gln Gln Arg Leu Ile Phe Ala Gly Lys
35 40 45
Gln Leu Glu Asp Gly Arg Thr Leu Ser Asp Tyr Asn Ile Gln Lys Glu
50 55 60
Ser Thr Leu His Leu Val Leu Arg Leu Arg Gly Gly Gly Gly Gly Gly
65 70 75 80
Ser Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val
85 90 95
Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro
100 105 110
Ala Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys
115 120 125
Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu
130 135 140
Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile
145 150 155 160
Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala
165 170 175
Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val
180 185 190
Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln
195 200 205
Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile
210 215 220
Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr
225 230 235 240
Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val
245 250 255
Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg
260 265 270
Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr
275 280 285
Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val
290 295 300
Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys
305 310 315 320
Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg
325 330 335
Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly
340 345 350
Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser
355 360 365
Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro
370 375 380
Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys
385 390 395 400
Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu
405 410 415
Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser
420 425 430
Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly
435 440 445
Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp
450 455 460
Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala
465 470 475 480
Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala
485 490 495
Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
500 505
<210> 150
<211> 1524
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 150
atgcaaatct tcgtgaagac cctgactggt aagaccatca ccctcgaggt ggagcccagt 60
gacaccatcg agaatgtcaa ggcaaagatc caagataagg aaggcatccc tcctgatcag 120
cagaggttga tctttgctgg gaaacagctg gaagatggac gcaccctgtc tgactacaac 180
atccagaaag agtccactct gcacttggtc ctgcgcttga gggggggtgg aggcggagga 240
tctacccaga acaaggccct gcccgagaac gtgaagtacg gcatcgtgct ggatgccggc 300
agcagccaca ccagcctgta catctacaag tggcctgccg agaaagaaaa cgacaccggc 360
gtggtgcatc aggtggaaga gtgcagagtg aagggccctg gcatcagcaa gttcgtgcag 420
aaagtgaacg agatcggcat ctacctgacc gactgcatgg aacgggccag ggaagtgatc 480
cccagaagcc agcaccagga aacccccgtg tatctgggag ccaccgccgg catgagactg 540
ctgagaatgg aaagcgagga actggccgac cgggtgctgg acgtggtgga aagaagcctg 600
agcaactacc cattcgattt tcaaggcgcc agaatcatca ccggccagga agaaggcgcc 660
tacggctgga tcaccatcaa ctacctgctg ggcaagttca gccagaagaa tcaggaaacc 720
ttcggcgccc tggacctggg cggagcttct acccaagtga ccttcgtgcc ccagaatcag 780
accatcgaga gccccgacaa cgccctgcag ttccggctgt acggcaagga ctacaatgtg 840
tacacccaca gctttctgtg ctacggaaag gaccaggctc tgtggcagaa gctggccaag 900
gacatccagg tggccagcaa cgagatcctg cgggaccctt gcttccaccc cggctacaag 960
aaagtcgtga acgtgtccga cctgtacaag accccctgca ccaagagatt cgagatgacc 1020
ctgcccttcc agcagttcga gatccagggc atcggcaatt accagcagtg ccaccagagc 1080
atcctggaac tgttcaacac cagctactgc ccctacagcc agtgcgcctt caacggcatc 1140
ttcctgccac ctctgcaggg ggatttcggc gccttcagcg ccttctactt cgtgatgaag 1200
ttcctgaacc tgaccagcga gaaggtgtcc caggaaaaag tgacagagat gatgaagaag 1260
ttctgcgccc agccctggga ggaaatcaag acctcctacg ctggcgtgaa agagaagtac 1320
ctgagcgagt actgcttcag cggcacctac atcctgagcc tgctgctgca gggctaccac 1380
ttcaccgccg atagctggga gcacatccac ttcatcggca agattcaggg cagcgacgcc 1440
ggctggacac tgggctacat gctgaatctg accaacatga tccccgccga gcagcccctg 1500
agcacacctc tgagccacag cacc 1524
<210> 151
<211> 618
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 151
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Ser Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Gly Gly Gly Gly Ser Thr
180 185 190
Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu Asp
195 200 205
Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala Glu
210 215 220
Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg Val
225 230 235 240
Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile Gly
245 250 255
Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro Arg
260 265 270
Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly Met
275 280 285
Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu Asp
290 295 300
Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly Ala
305 310 315 320
Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr Ile
325 330 335
Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe Gly
340 345 350
Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro Gln
355 360 365
Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu Tyr
370 375 380
Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly Lys
385 390 395 400
Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala Ser
405 410 415
Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys Val
420 425 430
Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe Glu
435 440 445
Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn Tyr
450 455 460
Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr Cys
465 470 475 480
Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu Gln
485 490 495
Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe Leu
500 505 510
Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met Met
515 520 525
Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr Ala
530 535 540
Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr Tyr
545 550 555 560
Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser Trp
565 570 575
Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly Trp
580 585 590
Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu Gln
595 600 605
Pro Leu Ser Thr Pro Leu Ser His Ser Thr
610 615
<210> 152
<211> 1854
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 152
gacgcccaca agagcgaggt ggcccaccgg ttcaaggacc tgggcgagga aaacttcaag 60
gccctggtgc tgatcgcctt cgcccagtac ctgcagcaga gccccttcga agatcacgta 120
aagttagtca acgaggttac ggaattcgca aagacatgcg ttgctgacga atccgctgag 180
aattgtgaca agagtttgca cactttattc ggagataagt tgtgtactgt agctactttg 240
agagagactt acggtgaaat ggctgactgc tgtgcaaaac aggaaccaga acgtaacgaa 300
tgtttccttc agcataagga tgataaccct aaccttccaa ggcttgttag gccagaagtc 360
gacgtgatgt gcaccgcctt ccatgataat gaagagactt ttcttaaaaa gtacctatac 420
gagattgcaa ggcgtcatcc atatttttac gccccagagc tgttgttttt cgcaaagaga 480
tacaaagctg catttactga gtgttgccaa gctgccgaca aggccgcttg tttgctacca 540
aagttggacg aattgagagg aggcggagga tctacccaga acaaggccct gcccgagaac 600
gtgaagtacg gcatcgtgct ggatgccggc agcagccaca ccagcctgta catctacaag 660
tggcctgccg agaaagaaaa cgacaccggc gtggtgcatc aggtggaaga gtgcagagtg 720
aagggccctg gcatcagcaa gttcgtgcag aaagtgaacg agatcggcat ctacctgacc 780
gactgcatgg aacgggccag ggaagtgatc cccagaagcc agcaccagga aacccccgtg 840
tatctgggag ccaccgccgg catgagactg ctgagaatgg aaagcgagga actggccgac 900
cgggtgctgg acgtggtgga aagaagcctg agcaactacc cattcgattt tcaaggcgcc 960
agaatcatca ccggccagga agaaggcgcc tacggctgga tcaccatcaa ctacctgctg 1020
ggcaagttca gccagaagaa tcaggaaacc ttcggcgccc tggacctggg cggagcttct 1080
acccaagtga ccttcgtgcc ccagaatcag accatcgaga gccccgacaa cgccctgcag 1140
ttccggctgt acggcaagga ctacaatgtg tacacccaca gctttctgtg ctacggaaag 1200
gaccaggctc tgtggcagaa gctggccaag gacatccagg tggccagcaa cgagatcctg 1260
cgggaccctt gcttccaccc cggctacaag aaagtcgtga acgtgtccga cctgtacaag 1320
accccctgca ccaagagatt cgagatgacc ctgcccttcc agcagttcga gatccagggc 1380
atcggcaatt accagcagtg ccaccagagc atcctggaac tgttcaacac cagctactgc 1440
ccctacagcc agtgcgcctt caacggcatc ttcctgccac ctctgcaggg ggatttcggc 1500
gccttcagcg ccttctactt cgtgatgaag ttcctgaacc tgaccagcga gaaggtgtcc 1560
caggaaaaag tgacagagat gatgaagaag ttctgcgccc agccctggga ggaaatcaag 1620
acctcctacg ctggcgtgaa agagaagtac ctgagcgagt actgcttcag cggcacctac 1680
atcctgagcc tgctgctgca gggctaccac ttcaccgccg atagctggga gcacatccac 1740
ttcatcggca agattcaggg cagcgacgcc ggctggacac tgggctacat gctgaatctg 1800
accaacatga tccccgccga gcagcccctg agcacacctc tgagccacag cacc 1854
<210> 153
<211> 625
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 153
Asp Glu Gly Lys Ala Ser Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser
1 5 10 15
Leu Gln Lys Phe Gly Glu Arg Ala Phe Lys Ala Trp Ala Val Ala Arg
20 25 30
Leu Ser Gln Arg Phe Pro Lys Ala Glu Phe Ala Glu Val Ser Lys Leu
35 40 45
Val Thr Asp Leu Thr Lys Val His Thr Glu Cys Cys His Gly Asp Leu
50 55 60
Leu Glu Cys Ala Asp Asp Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu
65 70 75 80
Asn Gln Asp Ser Ile Ser Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro
85 90 95
Leu Leu Glu Lys Ser His Cys Ile Ala Glu Val Glu Asn Asp Glu Met
100 105 110
Pro Ala Asp Leu Pro Ser Leu Ala Ala Asp Phe Val Glu Ser Lys Asp
115 120 125
Val Cys Lys Asn Tyr Ala Glu Ala Lys Asp Val Phe Leu Gly Met Phe
130 135 140
Leu Tyr Glu Tyr Ala Arg Arg His Pro Asp Tyr Ser Val Val Leu Leu
145 150 155 160
Leu Arg Leu Ala Lys Thr Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala
165 170 175
Ala Ala Asp Pro His Glu Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys
180 185 190
Pro Gly Gly Gly Gly Ser Thr Gln Asn Lys Ala Leu Pro Glu Asn Val
195 200 205
Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr
210 215 220
Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His
225 230 235 240
Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val
245 250 255
Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg
260 265 270
Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr
275 280 285
Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu
290 295 300
Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr
305 310 315 320
Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly
325 330 335
Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln
340 345 350
Lys Asn Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr
355 360 365
Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn
370 375 380
Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His
385 390 395 400
Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala
405 410 415
Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe
420 425 430
His Pro Gly Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr
435 440 445
Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu
450 455 460
Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu
465 470 475 480
Leu Phe Asn Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly
485 490 495
Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe
500 505 510
Tyr Phe Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln
515 520 525
Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu
530 535 540
Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu
545 550 555 560
Tyr Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr
565 570 575
His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile
580 585 590
Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr
595 600 605
Asn Met Ile Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser
610 615 620
Thr
625
<210> 154
<211> 1875
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 154
gacgagggta aggcatcatc tgccaagcag agattaaaat gtgcatcttt gcaaaaattt 60
ggagagagag cttttaaggc atgggctgtt gcccgactaa gccaaagatt cccaaaagcc 120
gaatttgctg aagtatccaa gctggtgact gatttgacta aagtacatac agaatgttgc 180
catggcgacc ttttagaatg tgctgatgac agagcagatt tggctaagta tatctgcgaa 240
aatcaagatt caatcagctc taagctgaag gaatgttgcg agaaaccact gttagaaaaa 300
tcgcattgta ttgctgaagt tgaaaatgat gagatgcctg ctgacttgcc ttctcttgcc 360
gctgattttg ttgagtcgaa ggatgtctgt aagaattatg ctgaagctaa agacgttttc 420
ctgggtatgt tcttatatga gtacgcaaga cgtcacccag attactctgt ggttctgcta 480
ctgagattgg ctaaaacata cgagacaacg ctggagaagt gctgtgctgc cgctgaccct 540
catgagtgct atgcaaaggt ttttgatgaa ttcaaaccag gaggcggagg atctacccag 600
aacaaggccc tgcccgagaa cgtgaagtac ggcatcgtgc tggatgccgg cagcagccac 660
accagcctgt acatctacaa gtggcctgcc gagaaagaaa acgacaccgg cgtggtgcat 720
caggtggaag agtgcagagt gaagggccct ggcatcagca agttcgtgca gaaagtgaac 780
gagatcggca tctacctgac cgactgcatg gaacgggcca gggaagtgat ccccagaagc 840
cagcaccagg aaacccccgt gtatctggga gccaccgccg gcatgagact gctgagaatg 900
gaaagcgagg aactggccga ccgggtgctg gacgtggtgg aaagaagcct gagcaactac 960
ccattcgatt ttcaaggcgc cagaatcatc accggccagg aagaaggcgc ctacggctgg 1020
atcaccatca actacctgct gggcaagttc agccagaaga atcaggaaac cttcggcgcc 1080
ctggacctgg gcggagcttc tacccaagtg accttcgtgc cccagaatca gaccatcgag 1140
agccccgaca acgccctgca gttccggctg tacggcaagg actacaatgt gtacacccac 1200
agctttctgt gctacggaaa ggaccaggct ctgtggcaga agctggccaa ggacatccag 1260
gtggccagca acgagatcct gcgggaccct tgcttccacc ccggctacaa gaaagtcgtg 1320
aacgtgtccg acctgtacaa gaccccctgc accaagagat tcgagatgac cctgcccttc 1380
cagcagttcg agatccaggg catcggcaat taccagcagt gccaccagag catcctggaa 1440
ctgttcaaca ccagctactg cccctacagc cagtgcgcct tcaacggcat cttcctgcca 1500
cctctgcagg gggatttcgg cgccttcagc gccttctact tcgtgatgaa gttcctgaac 1560
ctgaccagcg agaaggtgtc ccaggaaaaa gtgacagaga tgatgaagaa gttctgcgcc 1620
cagccctggg aggaaatcaa gacctcctac gctggcgtga aagagaagta cctgagcgag 1680
tactgcttca gcggcaccta catcctgagc ctgctgctgc agggctacca cttcaccgcc 1740
gatagctggg agcacatcca cttcatcggc aagattcagg gcagcgacgc cggctggaca 1800
ctgggctaca tgctgaatct gaccaacatg atccccgccg agcagcccct gagcacacct 1860
ctgagccaca gcacc 1875
<210> 155
<211> 439
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 155
Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu
1 5 10 15
Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala
20 25 30
Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg
35 40 45
Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile
50 55 60
Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro
65 70 75 80
Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly
85 90 95
Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu
100 105 110
Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly
115 120 125
Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr
130 135 140
Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Thr Arg Trp Phe Ser
145 150 155 160
Ile Val Pro Tyr Glu Thr Asn Asn Gln Glu Thr Phe Gly Ala Leu Asp
165 170 175
Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro Gln Asn Gln Thr
180 185 190
Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp
195 200 205
Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala
210 215 220
Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala Ser Asn Glu Ile
225 230 235 240
Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys Val Val Asn Val
245 250 255
Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe Glu Met Thr Leu
260 265 270
Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys
275 280 285
His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr Cys Pro Tyr Ser
290 295 300
Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe
305 310 315 320
Gly Ala Phe Ser Ala Phe Tyr Ser Val Met Lys Phe Leu Asn Leu Thr
325 330 335
Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met Met Lys Lys Phe
340 345 350
Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys
355 360 365
Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr Tyr Ile Leu Ser
370 375 380
Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser Trp Glu His Ile
385 390 395 400
His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly
405 410 415
Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu Gln Pro Leu Ser
420 425 430
Thr Pro Leu Ser His Ser Thr
435
<210> 156
<211> 1317
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 156
acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60
agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120
gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180
gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240
agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300
agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360
aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420
ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaccag atggttcagc 480
atcgtgccct acgagacaaa caatcaggaa accttcggcg ccctggacct gggcggagct 540
tctacccaag tgaccttcgt gccccagaat cagaccatcg agagccccga caacgccctg 600
cagttccggc tgtacggcaa ggactacaat gtgtacaccc acagctttct gtgctacgga 660
aaggaccagg ctctgtggca gaagctggcc aaggacatcc aggtggccag caacgagatc 720
ctgcgggacc cttgcttcca ccccggctac aagaaagtcg tgaacgtgtc cgacctgtac 780
aagaccccct gcaccaagag attcgagatg accctgccct tccagcagtt cgagatccag 840
ggcatcggca attaccagca gtgccaccag agcatcctgg aactgttcaa caccagctac 900
tgcccctaca gccagtgcgc cttcaacggc atcttcctgc cacctctgca gggggatttc 960
ggcgccttca gcgccttcta ctccgtgatg aagttcctga acctgaccag cgagaaggtg 1020
tcccaggaaa aagtgacaga gatgatgaag aagttctgcg cccagccctg ggaggaaatc 1080
aagacctcct acgctggcgt gaaagagaag tacctgagcg agtactgctt cagcggcacc 1140
tacatcctga gcctgctgct gcagggctac cacttcaccg ccgatagctg ggagcacatc 1200
cacttcatcg gcaagattca gggcagcgac gccggctgga cactgggcta catgctgaat 1260
ctgaccaaca tgatccccgc cgagcagccc ctgagcacac ctctgagcca cagcacc 1317
<210> 157
<211> 90
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 157
tcgcgatcct ggaaggcgtg cactgcgccc ctaccagcag cagcaccaag aaaacccagc 60
tgaccagcag cacccagaac aaggccctgc 90
<210> 158
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 158
tagaaggcac agtcgagg 18
<210> 159
<211> 66
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 159
ctggtcgcga tcctggaagg cgtgcactgc gcccctacca gcagcagcac ccagaacaag 60
gccctg 66
<210> 160
<211> 66
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 160
ctggtcgcga tcctggaagg cgtgcactgc gcccctacca gcagcagcac ccagaacaag 60
gccctg 66
<210> 161
<211> 57
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 161
ctggtcgcga tcctggaagg cgtgcactgc gcccctacca cccagaacaa ggccctg 57
<210> 162
<211> 75
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 162
ctggtcgcga tcctggaagg cgtgcactgc gcccctacca gcagcagcac caagaaaacc 60
cagaacaagg ccctg 75
<210> 163
<211> 84
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 163
ctggtcgcga tcctggaagg cgtgcactgc gcccctacca gcagcagcac caagaaaacc 60
cagctgaccc agaacaaggc cctg 84
<210> 164
<211> 75
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 164
ctggtcgcga tcctggaagg cgtgcactgc agcagcagca ccaagaaaac ccagctgacc 60
cagaacaagg ccctg 75
<210> 165
<211> 16
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 165
catacgattt aggtga 16
<210> 166
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 166
tagaaggcac agtcgagg 18
<210> 167
<211> 76
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 167
Met Gln Ile Phe Val Lys Thr Leu Thr Gly Lys Thr Ile Thr Leu Glu
1 5 10 15
Val Glu Pro Ser Asp Thr Ile Glu Asn Val Lys Ala Lys Ile Gln Asp
20 25 30
Lys Glu Gly Ile Pro Pro Asp Gln Gln Arg Leu Ile Phe Ala Gly Lys
35 40 45
Gln Leu Glu Asp Gly Arg Thr Leu Ser Asp Tyr Asn Ile Gln Lys Glu
50 55 60
Ser Thr Leu His Leu Val Leu Arg Leu Arg Gly Gly
65 70 75
<210> 168
<211> 105
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 168
Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln
1 5 10 15
Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr
20 25 30
Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser
35 40 45
Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr
50 55 60
Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys
65 70 75 80
His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro
85 90 95
Val Thr Lys Ser Phe Asn Arg Gly Glu
100 105
<210> 169
<211> 186
<212> PRT
<213> Homo sapiens
<400> 169
Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu
1 5 10 15
Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln
20 25 30
Gln Ser Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu
35 40 45
Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys
50 55 60
Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu
65 70 75 80
Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro
85 90 95
Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu
100 105 110
Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His
115 120 125
Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg
130 135 140
Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg
145 150 155 160
Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala
165 170 175
Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg
180 185
<210> 170
<211> 193
<212> PRT
<213> Homo sapiens
<400> 170
Asp Glu Gly Lys Ala Ser Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser
1 5 10 15
Leu Gln Lys Phe Gly Glu Arg Ala Phe Lys Ala Trp Ala Val Ala Arg
20 25 30
Leu Ser Gln Arg Phe Pro Lys Ala Glu Phe Ala Glu Val Ser Lys Leu
35 40 45
Val Thr Asp Leu Thr Lys Val His Thr Glu Cys Cys His Gly Asp Leu
50 55 60
Leu Glu Cys Ala Asp Asp Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu
65 70 75 80
Asn Gln Asp Ser Ile Ser Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro
85 90 95
Leu Leu Glu Lys Ser His Cys Ile Ala Glu Val Glu Asn Asp Glu Met
100 105 110
Pro Ala Asp Leu Pro Ser Leu Ala Ala Asp Phe Val Glu Ser Lys Asp
115 120 125
Val Cys Lys Asn Tyr Ala Glu Ala Lys Asp Val Phe Leu Gly Met Phe
130 135 140
Leu Tyr Glu Tyr Ala Arg Arg His Pro Asp Tyr Ser Val Val Leu Leu
145 150 155 160
Leu Arg Leu Ala Lys Thr Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala
165 170 175
Ala Ala Asp Pro His Glu Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys
180 185 190
Pro
<210> 171
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 171
ctgccgagaa agaacaggac accggcgtgg 30
<210> 172
<211> 30
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 172
ccacgccggt gtcctgttct ttctcggcag 30
<210> 173
<211> 29
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 173
cgtgccccag aatcaggcca tcgagagcc 29
<210> 174
<211> 29
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 174
ggctctcgat ggcctgattc tggggcacg 29
<210> 175
<211> 41
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 175
ggctacaaga aagtcgtgca ggtgtccgac ctgtacaaga c 41
<210> 176
<211> 41
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 176
gtcttgtaca ggtcggacac ctgcacgact ttcttgtagc c 41
<210> 177
<211> 35
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 177
gcatcctgga actgttccag accagctact gcccc 35
<210> 178
<211> 35
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 178
ggggcagtag ctggtctgga acagttccag gatgc 35
<210> 179
<211> 35
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 179
ccgtgatgaa gttcctgcag ctgaccagcg agaag 35
<210> 180
<211> 35
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 180
cttctcgctg gtcagctgca ggaacttcat cacgg 35
<210> 181
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 181
cactgggcta catgctgcag ctgaccaaca tgatcc 36
<210> 182
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 182
ggatcatgtt ggtcagctgc agcatgtagc ccagtg 36
<210> 183
<211> 39
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 183
ctacatcctg agcctgctgc agcagggcta ccacttcac 39
<210> 184
<211> 39
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 184
gtgaagtggt agccctgctg cagcaggctc aggatgtag 39
<210> 185
<211> 43
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 185
gagaagtacc tgagcgagtt ttgcttcagc ggcacctaca tcc 43
<210> 186
<211> 43
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 186
ggatgtaggt gccgctgaag caaaactcgc tcaggtactt ctc 43
<210> 187
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 187
gttcgagatc cagggcaccg gcaattacca gcagtg 36
<210> 188
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 188
cactgctggt aattgccggt gccctggatc tcgaac 36
<210> 189
<211> 37
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 189
cgccgatagc tgggagcaca tccacttcat cggcaag 37
<210> 190
<211> 37
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 190
cttgccgatg aagtggatgt gctcccagct atcggcg 37
<210> 191
<211> 120
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 191
gagatcggca tctacctgac cgactgcatg gaacgggcca tggaagtgat ccccagaagc 60
cagcaccagg aaacccccgt gtatctggga gccaccgccg gcatgagact gctgagaatg 120
<210> 192
<211> 25
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 192
gagatcggca tctacctgac cgact 25
<210> 193
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 193
cattctcagc agtctcat 18
<210> 194
<211> 120
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 194
cttcagcgcc ttctactccg tgatgaagtt cctgaacctg accagcgaga aggtgtccca 60
ggaaaaagtg acagagatga tgaagaagtt ctgcgcccag ccctgggagg aaatcaagac 120
<210> 195
<211> 19
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 195
cttcagcgcc ttctactcc 19
<210> 196
<211> 19
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 196
ggtcttgatt tcctcccag 19
<210> 197
<211> 119
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 197
ctgggaggaa atcaagacct cctacgctgg cgtgaaagag aagtacctga gcgagttctg 60
cttcagcggc acctacatcc tgagcctgct gctgcagggc taccacttca ccgccgata 119
<210> 198
<211> 119
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 198
ctgggaggaa atcaagacct cctacgctgg cgtgaaagag aagtacctga gcgagtactg 60
cttcagcggc acctacatcc tgagcctgct gcagcagggc taccacttca ccgccgata 119
<210> 199
<211> 119
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 199
ctgggaggaa atcaagacct cctacgctgg cgtgaaagag aagtacctga gcgagttctg 60
cttcagcggc acctacatcc tgagcctgct gcagcagggc taccacttca ccgccgata 119
<210> 200
<211> 19
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 200
ctgggaggaa atcaagacc 19
<210> 201
<211> 19
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 201
tatcggcggt gaagtggta 19
<210> 202
<211> 119
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 202
ctgggaggaa atcaagacct cctacgctgg cgtgaaagag aagtacctga gcgagtactg 60
cttcagcggc acctacatcc tgagcctgct gctgcagggc taccacttca ccgccgata 119
<210> 203
<211> 26
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 203
caccggccag gaagccggcg cctacg 26
<210> 204
<211> 26
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 204
cgtaggcgcc ggcttcctgg ccggtg 26
<210> 205
<211> 34
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 205
ggacctgggc ggagctgcta cccaagtgac cttc 34
<210> 206
<211> 34
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 206
gaaggtcact tgggtagcag ctccgcccag gtcc 34
<210> 207
<211> 80
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 207
ctggatcacc atcaactacc tgctgggcaa gttcagccag aagaccagat ggttcagcat 60
cgtgccctac gagacaaaca 80
<210> 208
<211> 69
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
primer"
<400> 208
tcacttgggt agaagctccg cccaggtcca gggcgccgaa ggtttcctga ttgtttgtct 60
cgtagggca 69
<210> 209
<211> 430
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 209
Ala Pro Thr Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly
1 5 10 15
Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys
20 25 30
Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu
35 40 45
Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val
50 55 60
Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu
65 70 75 80
Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala
85 90 95
Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp
100 105 110
Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp
115 120 125
Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly
130 135 140
Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln
145 150 155 160
Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr
165 170 175
Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln
180 185 190
Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu
195 200 205
Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile
210 215 220
Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly
225 230 235 240
Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr
245 250 255
Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly
260 265 270
Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn
275 280 285
Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu
290 295 300
Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val
305 310 315 320
Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val
325 330 335
Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys
340 345 350
Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe
355 360 365
Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr
370 375 380
Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser
385 390 395 400
Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile
405 410 415
Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425 430
<210> 210
<211> 1290
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 210
gcccctacca cccagaacaa ggccctgccc gagaacgtga agtacggcat cgtgctggat 60
gccggcagca gccacaccag cctgtacatc tacaagtggc ctgccgagaa agaaaacgac 120
accggcgtgg tgcatcaggt ggaagagtgc agagtgaagg gccctggcat cagcaagttc 180
gtgcagaaag tgaacgagat cggcatctac ctgaccgact gcatggaacg ggccatggaa 240
gtgatcccca gaagccagca ccaggaaacc cccgtgtatc tgggagccac cgccggcatg 300
agactgctga gaatggaaag cgaggaactg gccgaccggg tgctggacgt ggtggaaaga 360
agcctgagca actacccatt cgattttcaa ggcgccagaa tcatcaccgg ccaggaagaa 420
ggcgcctacg gctggatcac catcaactac ctgctgggca agttcagcca gaagaatcag 480
gaaaccttcg gcgccctgga cctgggcgga gcttctaccc aagtgacctt cgtgccccag 540
aatcagacca tcgagagccc cgacaacgcc ctgcagttcc ggctgtacgg caaggactac 600
aatgtgtaca cccacagctt tctgtgctac ggaaaggacc aggctctgtg gcagaagctg 660
gccaaggaca tccaggtggc cagcaacgag atcctgcggg acccttgctt ccaccccggc 720
tacaagaaag tcgtgaacgt gtccgacctg tacaagaccc cctgcaccaa gagattcgag 780
atgaccctgc ccttccagca gttcgagatc cagggcatcg gcaattacca gcagtgccac 840
cagagcatcc tggaactgtt caacaccagc tactgcccct acagccagtg cgccttcaac 900
ggcatcttcc tgccacctct gcagggggat ttcggcgcct tcagcgcctt ctacttcgtg 960
atgaagttcc tgaacctgac cagcgagaag gtgtcccagg aaaaagtgac agagatgatg 1020
aagaagttct gcgcccagcc ctgggaggaa atcaagacct cctacgctgg cgtgaaagag 1080
aagtacctga gcgagtactg cttcagcggc acctacatcc tgagcctgct gctgcagggc 1140
taccacttca ccgccgatag ctgggagcac atccacttca tcggcaagat tcagggcagc 1200
gacgccggct ggacactggg ctacatgctg aatctgacca acatgatccc cgccgagcag 1260
cccctgagca cacctctgag ccacagcacc 1290
<210> 211
<211> 430
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 211
Ala Pro Thr Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly
1 5 10 15
Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys
20 25 30
Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu
35 40 45
Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val
50 55 60
Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu
65 70 75 80
Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala
85 90 95
Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp
100 105 110
Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp
115 120 125
Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly
130 135 140
Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln
145 150 155 160
Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr
165 170 175
Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln
180 185 190
Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu
195 200 205
Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile
210 215 220
Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly
225 230 235 240
Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr
245 250 255
Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly
260 265 270
Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn
275 280 285
Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu
290 295 300
Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val
305 310 315 320
Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val
325 330 335
Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys
340 345 350
Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Phe Cys Phe
355 360 365
Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr
370 375 380
Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser
385 390 395 400
Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile
405 410 415
Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425 430
<210> 212
<211> 1290
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 212
gcccctacca cccagaacaa ggccctgccc gagaacgtga agtacggcat cgtgctggat 60
gccggcagca gccacaccag cctgtacatc tacaagtggc ctgccgagaa agaaaacgac 120
accggcgtgg tgcatcaggt ggaagagtgc agagtgaagg gccctggcat cagcaagttc 180
gtgcagaaag tgaacgagat cggcatctac ctgaccgact gcatggaacg ggccatggaa 240
gtgatcccca gaagccagca ccaggaaacc cccgtgtatc tgggagccac cgccggcatg 300
agactgctga gaatggaaag cgaggaactg gccgaccggg tgctggacgt ggtggaaaga 360
agcctgagca actacccatt cgattttcaa ggcgccagaa tcatcaccgg ccaggaagaa 420
ggcgcctacg gctggatcac catcaactac ctgctgggca agttcagcca gaagaatcag 480
gaaaccttcg gcgccctgga cctgggcgga gcttctaccc aagtgacctt cgtgccccag 540
aatcagacca tcgagagccc cgacaacgcc ctgcagttcc ggctgtacgg caaggactac 600
aatgtgtaca cccacagctt tctgtgctac ggaaaggacc aggctctgtg gcagaagctg 660
gccaaggaca tccaggtggc cagcaacgag atcctgcggg acccttgctt ccaccccggc 720
tacaagaaag tcgtgaacgt gtccgacctg tacaagaccc cctgcaccaa gagattcgag 780
atgaccctgc ccttccagca gttcgagatc cagggcatcg gcaattacca gcagtgccac 840
cagagcatcc tggaactgtt caacaccagc tactgcccct acagccagtg cgccttcaac 900
ggcatcttcc tgccacctct gcagggggat ttcggcgcct tcagcgcctt ctacttcgtg 960
atgaagttcc tgaacctgac cagcgagaag gtgtcccagg aaaaagtgac agagatgatg 1020
aagaagttct gcgcccagcc ctgggaggaa atcaagacct cctacgctgg cgtgaaagag 1080
aagtacctga gcgagttttg cttcagcggc acctacatcc tgagcctgct gctgcagggc 1140
taccacttca ccgccgatag ctgggagcac atccacttca tcggcaagat tcagggcagc 1200
gacgccggct ggacactggg ctacatgctg aatctgacca acatgatccc cgccgagcag 1260
cccctgagca cacctctgag ccacagcacc 1290
<210> 213
<211> 433
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 213
Ala Pro Thr Ser Ser Ser Thr Gln Asn Lys Ala Leu Pro Glu Asn Val
1 5 10 15
Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr
20 25 30
Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His
35 40 45
Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val
50 55 60
Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg
65 70 75 80
Ala Met Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr
85 90 95
Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu
100 105 110
Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr
115 120 125
Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly
130 135 140
Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln
145 150 155 160
Lys Asn Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr
165 170 175
Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn
180 185 190
Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His
195 200 205
Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala
210 215 220
Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe
225 230 235 240
His Pro Gly Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr
245 250 255
Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu
260 265 270
Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu
275 280 285
Leu Phe Asn Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly
290 295 300
Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe
305 310 315 320
Tyr Phe Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln
325 330 335
Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu
340 345 350
Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu
355 360 365
Phe Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr
370 375 380
His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile
385 390 395 400
Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr
405 410 415
Asn Met Ile Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser
420 425 430
Thr
<210> 214
<211> 1299
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 214
gcccctacca gcagcagcac ccagaacaag gccctgcccg agaacgtgaa gtacggcatc 60
gtgctggatg ccggcagcag ccacaccagc ctgtacatct acaagtggcc tgccgagaaa 120
gaaaacgaca ccggcgtggt gcatcaggtg gaagagtgca gagtgaaggg ccctggcatc 180
agcaagttcg tgcagaaagt gaacgagatc ggcatctacc tgaccgactg catggaacgg 240
gccatggaag tgatccccag aagccagcac caggaaaccc ccgtgtatct gggagccacc 300
gccggcatga gactgctgag aatggaaagc gaggaactgg ccgaccgggt gctggacgtg 360
gtggaaagaa gcctgagcaa ctacccattc gattttcaag gcgccagaat catcaccggc 420
caggaagaag gcgcctacgg ctggatcacc atcaactacc tgctgggcaa gttcagccag 480
aagaatcagg aaaccttcgg cgccctggac ctgggcggag cttctaccca agtgaccttc 540
gtgccccaga atcagaccat cgagagcccc gacaacgccc tgcagttccg gctgtacggc 600
aaggactaca atgtgtacac ccacagcttt ctgtgctacg gaaaggacca ggctctgtgg 660
cagaagctgg ccaaggacat ccaggtggcc agcaacgaga tcctgcggga cccttgcttc 720
caccccggct acaagaaagt cgtgaacgtg tccgacctgt acaagacccc ctgcaccaag 780
agattcgaga tgaccctgcc cttccagcag ttcgagatcc agggcatcgg caattaccag 840
cagtgccacc agagcatcct ggaactgttc aacaccagct actgccccta cagccagtgc 900
gccttcaacg gcatcttcct gccacctctg cagggggatt tcggcgcctt cagcgccttc 960
tacttcgtga tgaagttcct gaacctgacc agcgagaagg tgtcccagga aaaagtgaca 1020
gagatgatga agaagttctg cgcccagccc tgggaggaaa tcaagacctc ctacgctggc 1080
gtgaaagaga agtacctgag cgagttctgc ttcagcggca cctacatcct gagcctgctg 1140
ctgcagggct accacttcac cgccgatagc tgggagcaca tccacttcat cggcaagatt 1200
cagggcagcg acgccggctg gacactgggc tacatgctga atctgaccaa catgatcccc 1260
gccgagcagc ccctgagcac acctctgagc cacagcacc 1299
<210> 215
<211> 442
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 215
Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Thr Ser Ser Thr
1 5 10 15
Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu Asp
20 25 30
Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala Glu
35 40 45
Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg Val
50 55 60
Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile Gly
65 70 75 80
Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu Val Ile Pro Arg
85 90 95
Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly Met
100 105 110
Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu Asp
115 120 125
Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly Ala
130 135 140
Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr Ile
145 150 155 160
Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe Gly
165 170 175
Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro Gln
180 185 190
Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu Tyr
195 200 205
Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly Lys
210 215 220
Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala Ser
225 230 235 240
Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys Val
245 250 255
Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe Glu
260 265 270
Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn Tyr
275 280 285
Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr Cys
290 295 300
Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu Gln
305 310 315 320
Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe Leu
325 330 335
Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met Met
340 345 350
Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr Ala
355 360 365
Gly Val Asn Glu Lys Tyr Leu Ser Glu Phe Cys Phe Ser Gly Thr Tyr
370 375 380
Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser Trp
385 390 395 400
Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly Trp
405 410 415
Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu Gln
420 425 430
Pro Leu Ser Thr Pro Leu Ser His Ser Thr
435 440
<210> 216
<211> 1326
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 216
gcccctacca gcagcagcac caagaaaacc cagctgacca gcagcaccca gaacaaggcc 60
ctgcccgaga acgtgaagta cggcatcgtg ctggatgccg gcagcagcca caccagcctg 120
tacatctaca agtggcctgc cgagaaagaa aacgacaccg gcgtggtgca tcaggtggaa 180
gagtgcagag tgaagggccc tggcatcagc aagttcgtgc agaaagtgaa cgagatcggc 240
atctacctga ccgactgcat ggaacgggcc atggaagtga tccccagaag ccagcaccag 300
gaaacccccg tgtatctggg agccaccgcc ggcatgagac tgctgagaat ggaaagcgag 360
gaactggccg accgggtgct ggacgtggtg gaaagaagcc tgagcaacta cccattcgat 420
tttcaaggcg ccagaatcat caccggccag gaagaaggcg cctacggctg gatcaccatc 480
aactacctgc tgggcaagtt cagccagaag aatcaggaaa ccttcggcgc cctggacctg 540
ggcggagctt ctacccaagt gaccttcgtg ccccagaatc agaccatcga gagccccgac 600
aacgccctgc agttccggct gtacggcaag gactacaatg tgtacaccca cagctttctg 660
tgctacggaa aggaccaggc tctgtggcag aagctggcca aggacatcca ggtggccagc 720
aacgagatcc tgcgggaccc ttgcttccac cccggctaca agaaagtcgt gaacgtgtcc 780
gacctgtaca agaccccctg caccaagaga ttcgagatga ccctgccctt ccagcagttc 840
gagatccagg gcatcggcaa ttaccagcag tgccaccaga gcatcctgga actgttcaac 900
accagctact gcccctacag ccagtgcgcc ttcaacggca tcttcctgcc acctctgcag 960
ggggatttcg gcgccttcag cgccttctac ttcgtgatga agttcctgaa cctgaccagc 1020
gagaaggtgt cccaggaaaa agtgacagag atgatgaaga agttctgcgc ccaaccctgg 1080
gaggaaatca agacctccta cgctggcgtg aacgagaagt acctgagcga gttttgcttc 1140
agcggcacct acatcctgag cctgctgctg cagggctacc acttcaccgc cgatagctgg 1200
gagcacatcc acttcatcgg caagattcag ggcagcgacg ccggctggac actgggctac 1260
atgctgaatc tgaccaacat gatccccgcc gagcagcccc tgagcacacc tctgagccac 1320
agcacc 1326
<210> 217
<211> 430
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 217
Ala Pro Thr Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly
1 5 10 15
Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys
20 25 30
Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu
35 40 45
Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val
50 55 60
Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu
65 70 75 80
Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala
85 90 95
Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp
100 105 110
Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp
115 120 125
Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly
130 135 140
Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln
145 150 155 160
Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr
165 170 175
Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln
180 185 190
Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu
195 200 205
Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile
210 215 220
Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly
225 230 235 240
Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr
245 250 255
Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly
260 265 270
Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn
275 280 285
Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu
290 295 300
Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val
305 310 315 320
Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val
325 330 335
Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys
340 345 350
Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Phe Cys Phe
355 360 365
Ser Gly Thr Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr His Phe Thr
370 375 380
Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser
385 390 395 400
Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile
405 410 415
Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425 430
<210> 218
<211> 1290
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 218
gcccctacca cccagaacaa ggccctgccc gagaacgtga agtacggcat cgtgctggat 60
gccggcagca gccacaccag cctgtacatc tacaagtggc ctgccgagaa agaaaacgac 120
accggcgtgg tgcatcaggt ggaagagtgc agagtgaagg gccctggcat cagcaagttc 180
gtgcagaaag tgaacgagat cggcatctac ctgaccgact gcatggaacg ggccatggaa 240
gtgatcccca gaagccagca ccaggaaacc cccgtgtatc tgggagccac cgccggcatg 300
agactgctga gaatggaaag cgaggaactg gccgaccggg tgctggacgt ggtggaaaga 360
agcctgagca actacccatt cgattttcaa ggcgccagaa tcatcaccgg ccaggaagaa 420
ggcgcctacg gctggatcac catcaactac ctgctgggca agttcagcca gaagaatcag 480
gaaaccttcg gcgccctgga cctgggcgga gcttctaccc aagtgacctt cgtgccccag 540
aatcagacca tcgagagccc cgacaacgcc ctgcagttcc ggctgtacgg caaggactac 600
aatgtgtaca cccacagctt tctgtgctac ggaaaggacc aggctctgtg gcagaagctg 660
gccaaggaca tccaggtggc cagcaacgag atcctgcggg acccttgctt ccaccccggc 720
tacaagaaag tcgtgaacgt gtccgacctg tacaagaccc cctgcaccaa gagattcgag 780
atgaccctgc ccttccagca gttcgagatc cagggcatcg gcaattacca gcagtgccac 840
cagagcatcc tggaactgtt caacaccagc tactgcccct acagccagtg cgccttcaac 900
ggcatcttcc tgccacctct gcagggggat ttcggcgcct tcagcgcctt ctacttcgtg 960
atgaagttcc tgaacctgac cagcgagaag gtgtcccagg aaaaagtgac agagatgatg 1020
aagaagttct gcgcccagcc ctgggaggaa atcaagacct cctacgctgg cgtgaaagag 1080
aagtacctga gcgagttctg cttcagcggc acctacatcc tgagcctgct gcagcagggc 1140
taccacttca ccgccgatag ctgggagcac atccacttca tcggcaagat tcagggcagc 1200
gacgccggct ggacactggg ctacatgctg aatctgacca acatgatccc cgccgagcag 1260
cccctgagca cacctctgag ccacagcacc 1290
<210> 219
<211> 433
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 219
Ala Pro Thr Ser Ser Ser Thr Gln Asn Lys Ala Leu Pro Glu Asn Val
1 5 10 15
Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr
20 25 30
Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His
35 40 45
Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val
50 55 60
Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg
65 70 75 80
Ala Met Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr
85 90 95
Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu
100 105 110
Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr
115 120 125
Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly
130 135 140
Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln
145 150 155 160
Lys Asn Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr
165 170 175
Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn
180 185 190
Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His
195 200 205
Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala
210 215 220
Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe
225 230 235 240
His Pro Gly Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr
245 250 255
Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu
260 265 270
Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu
275 280 285
Leu Phe Asn Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly
290 295 300
Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe
305 310 315 320
Tyr Phe Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln
325 330 335
Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu
340 345 350
Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu
355 360 365
Phe Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr
370 375 380
His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile
385 390 395 400
Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr
405 410 415
Asn Met Ile Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser
420 425 430
Thr
<210> 220
<211> 1299
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 220
gcccctacca gcagcagcac ccagaacaag gccctgcccg agaacgtgaa gtacggcatc 60
gtgctggatg ccggcagcag ccacaccagc ctgtacatct acaagtggcc tgccgagaaa 120
gaaaacgaca ccggcgtggt gcatcaggtg gaagagtgca gagtgaaggg ccctggcatc 180
agcaagttcg tgcagaaagt gaacgagatc ggcatctacc tgaccgactg catggaacgg 240
gccatggaag tgatccccag aagccagcac caggaaaccc ccgtgtatct gggagccacc 300
gccggcatga gactgctgag aatggaaagc gaggaactgg ccgaccgggt gctggacgtg 360
gtggaaagaa gcctgagcaa ctacccattc gattttcaag gcgccagaat catcaccggc 420
caggaagaag gcgcctacgg ctggatcacc atcaactacc tgctgggcaa gttcagccag 480
aagaatcagg aaaccttcgg cgccctggac ctgggcggag cttctaccca agtgaccttc 540
gtgccccaga atcagaccat cgagagcccc gacaacgccc tgcagttccg gctgtacggc 600
aaggactaca atgtgtacac ccacagcttt ctgtgctacg gaaaggacca ggctctgtgg 660
cagaagctgg ccaaggacat ccaggtggcc agcaacgaga tcctgcggga cccttgcttc 720
caccccggct acaagaaagt cgtgaacgtg tccgacctgt acaagacccc ctgcaccaag 780
agattcgaga tgaccctgcc cttccagcag ttcgagatcc agggcatcgg caattaccag 840
cagtgccacc agagcatcct ggaactgttc aacaccagct actgccccta cagccagtgc 900
gccttcaacg gcatcttcct gccacctctg cagggggatt tcggcgcctt cagcgccttc 960
tacttcgtga tgaagttcct gaacctgacc agcgagaagg tgtcccagga aaaagtgaca 1020
gagatgatga agaagttctg cgcccagccc tgggaggaaa tcaagacctc ctacgctggc 1080
gtgaaagaga agtacctgag cgagttctgc ttcagcggca cctacatcct gagcctgctg 1140
cagcagggct accacttcac cgccgatagc tgggagcaca tccacttcat cggcaagatt 1200
cagggcagcg acgccggctg gacactgggc tacatgctga atctgaccaa catgatcccc 1260
gccgagcagc ccctgagcac acctctgagc cacagcacc 1299
<210> 221
<211> 430
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 221
Ala Pro Thr Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly
1 5 10 15
Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys
20 25 30
Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu
35 40 45
Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val
50 55 60
Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu
65 70 75 80
Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala
85 90 95
Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp
100 105 110
Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp
115 120 125
Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly
130 135 140
Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln
145 150 155 160
Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr
165 170 175
Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln
180 185 190
Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu
195 200 205
Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile
210 215 220
Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly
225 230 235 240
Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr
245 250 255
Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly
260 265 270
Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn
275 280 285
Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu
290 295 300
Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Ser Val
305 310 315 320
Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val
325 330 335
Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys
340 345 350
Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe
355 360 365
Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr
370 375 380
Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser
385 390 395 400
Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile
405 410 415
Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425 430
<210> 222
<211> 1290
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 222
gcccctacca cccagaacaa ggccctgccc gagaacgtga agtacggcat cgtgctggat 60
gccggcagca gccacaccag cctgtacatc tacaagtggc ctgccgagaa agaaaacgac 120
accggcgtgg tgcatcaggt ggaagagtgc agagtgaagg gccctggcat cagcaagttc 180
gtgcagaaag tgaacgagat cggcatctac ctgaccgact gcatggaacg ggccatggaa 240
gtgatcccca gaagccagca ccaggaaacc cccgtgtatc tgggagccac cgccggcatg 300
agactgctga gaatggaaag cgaggaactg gccgaccggg tgctggacgt ggtggaaaga 360
agcctgagca actacccatt cgattttcaa ggcgccagaa tcatcaccgg ccaggaagaa 420
ggcgcctacg gctggatcac catcaactac ctgctgggca agttcagcca gaagaatcag 480
gaaaccttcg gcgccttgga cctgggcgga gcttctaccc aagtgacctt cgtgccccag 540
aatcagacca tcgagagccc cgacaacgcc ctgcagttcc ggctgtacgg caaggactac 600
aatgtgtaca cccacagctt tctgtgctac ggaaaggacc aggctctgtg gcagaagctg 660
gccaaggaca tccaggtggc cagcaacgag atcctgcggg acccttgctt ccaccccggc 720
tacaagaaag tcgtgaacgt gtccgacctg tacaagaccc cctgcaccaa gagattcgag 780
atgaccctgc ccttccagca gttcgagatc cagggcatcg gcaattacca gcagtgccac 840
cagagcatcc tggaactgtt caacaccagc tactgcccct acagccagtg cgccttcaac 900
ggcatcttcc tgccacctct gcagggggat ttcggcgcct tcagcgcctt ctactccgtg 960
atgaagttcc tgaacctgac cagcgagaag gtgtcccagg aaaaagtgac agagatgatg 1020
aagaagttct gcgcccagcc ctgggaggaa atcaagacct cctacgctgg cgtgaaagag 1080
aagtacctga gcgagtactg cttcagcggc acctacatcc tgagcctgct gctgcagggc 1140
taccacttca ccgccgatag ctgggagcac atccacttca tcggcaagat tcagggcagc 1200
gacgccggct ggacactggg ttacatgctg aatctgacca acatgatccc cgccgagcag 1260
cccctgagca cacctctgag ccacagcacc 1290
<210> 223
<211> 433
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 223
Ala Pro Thr Ser Ser Ser Thr Gln Asn Lys Ala Leu Pro Glu Asn Val
1 5 10 15
Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr
20 25 30
Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His
35 40 45
Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val
50 55 60
Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg
65 70 75 80
Ala Met Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr
85 90 95
Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu
100 105 110
Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr
115 120 125
Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly
130 135 140
Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln
145 150 155 160
Lys Asn Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr
165 170 175
Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn
180 185 190
Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His
195 200 205
Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala
210 215 220
Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe
225 230 235 240
His Pro Gly Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr
245 250 255
Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu
260 265 270
Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu
275 280 285
Leu Phe Asn Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly
290 295 300
Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe
305 310 315 320
Tyr Ser Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln
325 330 335
Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu
340 345 350
Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu
355 360 365
Tyr Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr
370 375 380
His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile
385 390 395 400
Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr
405 410 415
Asn Met Ile Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser
420 425 430
Thr
<210> 224
<211> 1299
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 224
gcccctacca gcagcagcac ccagaacaag gccctgcccg agaacgtgaa gtacggcatc 60
gtgctggatg ccggcagcag ccacaccagc ctgtacatct acaagtggcc tgccgagaaa 120
gaaaacgaca ccggcgtggt gcatcaggtg gaagagtgca gagtgaaggg ccctggcatc 180
agcaagttcg tgcagaaagt gaacgagatc ggcatctacc tgaccgactg catggaacgg 240
gccatggaag tgatccccag aagccagcac caggaaaccc ccgtgtatct gggagccacc 300
gccggcatga gactgctgag aatggaaagc gaggaactgg ccgaccgggt gctggacgtg 360
gtggaaagaa gcctgagcaa ctacccattc gattttcaag gcgccagaat catcaccggc 420
caggaagaag gcgcctacgg ctggatcacc atcaactacc tgctgggcaa gttcagccag 480
aagaatcagg aaaccttcgg cgccttggac ctgggcggag cttctaccca agtgaccttc 540
gtgccccaga atcagaccat cgagagcccc gacaacgccc tgcagttccg gctgtacggc 600
aaggactaca atgtgtacac ccacagcttt ctgtgctacg gaaaggacca ggctctgtgg 660
cagaagctgg ccaaggacat ccaggtggcc agcaacgaga tcctgcggga cccttgcttc 720
caccccggct acaagaaagt cgtgaacgtg tccgacctgt acaagacccc ctgcaccaag 780
agattcgaga tgaccctgcc cttccagcag ttcgagatcc agggcatcgg caattaccag 840
cagtgccacc agagcatcct ggaactgttc aacaccagct actgccccta cagccagtgc 900
gccttcaacg gcatcttcct gccacctctg cagggggatt tcggcgcctt cagcgccttc 960
tactccgtga tgaagttcct gaacctgacc agcgagaagg tgtcccagga aaaagtgaca 1020
gagatgatga agaagttctg cgcccagccc tgggaggaaa tcaagacctc ctacgctggc 1080
gtgaaagaga agtacctgag cgagtactgc ttcagcggca cctacatcct gagcctgctg 1140
ctgcagggct accacttcac cgccgatagc tgggagcaca tccacttcat cggcaagatt 1200
cagggcagcg acgccggctg gacactgggt tacatgctga atctgaccaa catgatcccc 1260
gccgagcagc ccctgagcac acctctgagc cacagcacc 1299
<210> 225
<211> 430
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 225
Ala Pro Thr Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly
1 5 10 15
Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys
20 25 30
Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu
35 40 45
Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val
50 55 60
Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu
65 70 75 80
Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala
85 90 95
Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp
100 105 110
Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp
115 120 125
Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly
130 135 140
Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln
145 150 155 160
Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr
165 170 175
Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln
180 185 190
Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu
195 200 205
Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile
210 215 220
Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly
225 230 235 240
Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr
245 250 255
Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly
260 265 270
Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn
275 280 285
Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu
290 295 300
Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val
305 310 315 320
Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val
325 330 335
Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys
340 345 350
Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Phe Cys Phe
355 360 365
Ser Gly Thr Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr His Phe Thr
370 375 380
Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser
385 390 395 400
Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile
405 410 415
Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425 430
<210> 226
<211> 1290
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 226
gcccctacca cccagaacaa ggccctgccc gagaacgtga agtacggcat cgtgctggat 60
gccggcagca gccacaccag cctgtacatc tacaagtggc ctgccgagaa agaaaacgac 120
accggcgtgg tgcatcaggt ggaagagtgc agagtgaagg gccctggcat cagcaagttc 180
gtgcagaaag tgaacgagat cggcatctac ctgaccgact gcatggaacg ggccagggaa 240
gtgatcccca gaagccagca ccaggaaacc cccgtgtatc tgggagccac cgccggcatg 300
agactgctga gaatggaaag cgaggaactg gccgaccggg tgctggacgt ggtggaaaga 360
agcctgagca actacccatt cgattttcaa ggcgccagaa tcatcaccgg ccaggaagaa 420
ggcgcctacg gctggatcac catcaactac ctgctgggca agttcagcca gaagaatcag 480
gaaaccttcg gcgccctgga cctgggcgga gcttctaccc aagtgacctt cgtgccccag 540
aatcagacca tcgagagccc cgacaacgcc ctgcagttcc ggctgtacgg caaggactac 600
aatgtgtaca cccacagctt tctgtgctac ggaaaggacc aggctctgtg gcagaagctg 660
gccaaggaca tccaggtggc cagcaacgag atcctgcggg acccttgctt ccaccccggc 720
tacaagaaag tcgtgaacgt gtccgacctg tacaagaccc cctgcaccaa gagattcgag 780
atgaccctgc ccttccagca gttcgagatc cagggcatcg gcaattacca gcagtgccac 840
cagagcatcc tggaactgtt caacaccagc tactgcccct acagccagtg cgccttcaac 900
ggcatcttcc tgccacctct gcagggggat ttcggcgcct tcagcgcctt ctacttcgtg 960
atgaagttcc tgaacctgac cagcgagaag gtgtcccagg aaaaagtgac agagatgatg 1020
aagaagttct gcgcccagcc ctgggaggaa atcaagacct cctacgctgg cgtgaaagag 1080
aagtacctga gcgagttttg cttcagcggc acctacatcc tgagcctgct gcagcagggc 1140
taccacttca ccgccgatag ctgggagcac atccacttca tcggcaagat tcagggcagc 1200
gacgccggct ggacactggg ctacatgctg aatctgacca acatgatccc cgccgagcag 1260
cccctgagca cacctctgag ccacagcacc 1290
<210> 227
<211> 433
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 227
Ala Pro Thr Ser Ser Ser Thr Gln Asn Lys Ala Leu Pro Glu Asn Val
1 5 10 15
Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr
20 25 30
Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His
35 40 45
Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val
50 55 60
Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg
65 70 75 80
Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr
85 90 95
Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu
100 105 110
Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr
115 120 125
Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly
130 135 140
Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln
145 150 155 160
Lys Asn Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr
165 170 175
Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn
180 185 190
Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His
195 200 205
Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala
210 215 220
Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe
225 230 235 240
His Pro Gly Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr
245 250 255
Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu
260 265 270
Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu
275 280 285
Leu Phe Asn Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly
290 295 300
Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe
305 310 315 320
Tyr Phe Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln
325 330 335
Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu
340 345 350
Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu
355 360 365
Phe Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr
370 375 380
His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile
385 390 395 400
Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr
405 410 415
Asn Met Ile Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser
420 425 430
Thr
<210> 228
<211> 1299
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 228
gcccctacca gcagcagcac ccagaacaag gccctgcccg agaacgtgaa gtacggcatc 60
gtgctggatg ccggcagcag ccacaccagc ctgtacatct acaagtggcc tgccgagaaa 120
gaaaacgaca ccggcgtggt gcatcaggtg gaagagtgca gagtgaaggg ccctggcatc 180
agcaagttcg tgcagaaagt gaacgagatc ggcatctacc tgaccgactg catggaacgg 240
gccagggaag tgatccccag aagccagcac caggaaaccc ccgtgtatct gggagccacc 300
gccggcatga gactgctgag aatggaaagc gaggaactgg ccgaccgggt gctggacgtg 360
gtggaaagaa gcctgagcaa ctacccattc gattttcaag gcgccagaat catcaccggc 420
caggaagaag gcgcctacgg ctggatcacc atcaactacc tgctgggcaa gttcagccag 480
aagaatcagg aaaccttcgg cgccctggac ctgggcggag cttctaccca agtgaccttc 540
gtgccccaga atcagaccat cgagagcccc gacaacgccc tgcagttccg gctgtacggc 600
aaggactaca atgtgtacac ccacagcttt ctgtgctacg gaaaggacca ggctctgtgg 660
cagaagctgg ccaaggacat ccaggtggcc agcaacgaga tcctgcggga cccttgcttc 720
caccccggct acaagaaagt cgtgaacgtg tccgacctgt acaagacccc ctgcaccaag 780
agattcgaga tgaccctgcc cttccagcag ttcgagatcc agggcatcgg caattaccag 840
cagtgccacc agagcatcct ggaactgttc aacaccagct actgccccta cagccagtgc 900
gccttcaacg gcatcttcct gccacctctg cagggggatt tcggcgcctt cagcgccttc 960
tacttcgtga tgaagttcct gaacctgacc agcgagaagg tgtcccagga aaaagtgaca 1020
gagatgatga agaagttctg cgcccagccc tgggaggaaa tcaagacctc ctacgctggc 1080
gtgaaagaga agtacctgag cgagttttgc ttcagcggca cctacatcct gagcctgctg 1140
cagcagggct accacttcac cgccgatagc tgggagcaca tccacttcat cggcaagatt 1200
cagggcagcg acgccggctg gacactgggc tacatgctga atctgaccaa catgatcccc 1260
gccgagcagc ccctgagcac acctctgagc cacagcacc 1299
<210> 229
<211> 430
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 229
Ala Pro Thr Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly
1 5 10 15
Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys
20 25 30
Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu
35 40 45
Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val
50 55 60
Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu
65 70 75 80
Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala
85 90 95
Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp
100 105 110
Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp
115 120 125
Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly
130 135 140
Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln
145 150 155 160
Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr
165 170 175
Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln
180 185 190
Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu
195 200 205
Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile
210 215 220
Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly
225 230 235 240
Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr
245 250 255
Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly
260 265 270
Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn
275 280 285
Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu
290 295 300
Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Ser Val
305 310 315 320
Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val
325 330 335
Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys
340 345 350
Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe
355 360 365
Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr
370 375 380
Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser
385 390 395 400
Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile
405 410 415
Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425 430
<210> 230
<211> 1290
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 230
gcccctacca cccagaacaa ggccctgccc gagaacgtga agtacggcat cgtgctggac 60
gccggctcct cccacacctc cctgtacatc tacaagtggc ctgccgagaa agaaaacgac 120
accggcgtgg tgcaccaagt ggaagagtgc agagtgaagg gccccggcat ctccaagttc 180
gtgcagaaag tgaacgagat cggcatctac ctgaccgact gcatggaacg ggccagagaa 240
gtgatccctc ggtcccagca ccaggaaacc cctgtctacc tgggcgccac cgccggcatg 300
cggctgctgc ggatggaatc cgaggaactg gccgaccggg tgctggacgt ggtggaacgg 360
tccctgtcca actacccatt cgattttcaa ggcgccagaa tcatcaccgg ccaggaagag 420
ggcgcctacg gctggatcac catcaactac ctgctgggca agttctccca gaagaatcag 480
gaaaccttcg gcgccctgga cctgggcgga gccagcaccc aagtcacatt cgtgccccag 540
aaccagacca tcgagagccc cgacaacgcc ctgcagttcc ggctgtacgg caaggactac 600
aacgtgtaca cccacagctt tctgtgctac ggcaaggacc aggccctgtg gcagaagctg 660
gccaaggaca tccaagtggc ctccaacgag atcctgcggg acccctgctt ccaccccggc 720
tacaagaaag tggtcaacgt gtccgacctg tacaagaccc cttgcaccaa gagattcgag 780
atgaccctgc ccttccagca gttcgagatc cagggcatcg gcaactacca gcagtgccac 840
cagtccatcc tggaactgtt caacacctcc tactgcccct actcccagtg cgccttcaac 900
ggcatcttcc tgcctccact gcagggcgac ttcggcgcct tctccgcctt ctactccgtg 960
atgaagttcc tgaacctgac ctccgagaaa gtgtcccagg aaaaagtgac cgagatgatg 1020
aagaagttct gcgcccagcc ctgggaggaa atcaagacct cctacgctgg cgtgaaagag 1080
aagtacctgt ccgagtactg cttctccggc acctacatcc tgtccctgct gctgcagggc 1140
taccacttca ccgccgacag ctgggagcac atccacttca tcggcaagat ccagggatcc 1200
gacgctggct ggaccctggg ctacatgctg aatctgacca acatgatccc cgccgagcag 1260
cccctgtcca cccctctgtc tcactccacc 1290
<210> 231
<211> 433
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 231
Ala Pro Thr Ser Ser Ser Thr Gln Asn Lys Ala Leu Pro Glu Asn Val
1 5 10 15
Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr
20 25 30
Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His
35 40 45
Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val
50 55 60
Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg
65 70 75 80
Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr
85 90 95
Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu
100 105 110
Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr
115 120 125
Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly
130 135 140
Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln
145 150 155 160
Lys Asn Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr
165 170 175
Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn
180 185 190
Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His
195 200 205
Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala
210 215 220
Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe
225 230 235 240
His Pro Gly Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr
245 250 255
Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu
260 265 270
Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu
275 280 285
Leu Phe Asn Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly
290 295 300
Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe
305 310 315 320
Tyr Ser Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln
325 330 335
Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu
340 345 350
Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu
355 360 365
Tyr Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr
370 375 380
His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile
385 390 395 400
Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr
405 410 415
Asn Met Ile Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser
420 425 430
Thr
<210> 232
<211> 1299
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 232
gcccctacca gcagcagcac ccagaacaag gccctgcccg agaacgtgaa gtacggcatc 60
gtgctggatg ccggcagcag ccacaccagc ctgtacatct acaagtggcc tgccgagaaa 120
gaaaacgaca ccggcgtggt gcatcaggtg gaagagtgca gagtgaaggg ccctggcatc 180
agcaagttcg tgcagaaagt gaacgagatc ggcatctacc tgaccgactg catggaacgg 240
gccagggaag tgatccccag aagccagcac caggaaaccc ccgtgtatct gggagccacc 300
gccggcatga gactgctgag aatggaaagc gaggaactgg ccgaccgggt gctggacgtg 360
gtggaaagaa gcctgagcaa ctacccattc gattttcaag gcgccagaat catcaccggc 420
caggaagaag gcgcctacgg ctggatcacc atcaactacc tgctgggcaa gttcagccag 480
aagaatcagg aaaccttcgg cgccttggac ctgggcggag cttctaccca agtgaccttc 540
gtgccccaga atcagaccat cgagagcccc gacaacgccc tgcagttccg gctgtacggc 600
aaggactaca atgtgtacac ccacagcttt ctgtgctacg gaaaggacca ggctctgtgg 660
cagaagctgg ccaaggacat ccaggtggcc agcaacgaga tcctgcggga cccttgcttc 720
caccccggct acaagaaagt cgtgaacgtg tccgacctgt acaagacccc ctgcaccaag 780
agattcgaga tgaccctgcc cttccagcag ttcgagatcc agggcatcgg caattaccag 840
cagtgccacc agagcatcct ggaactgttc aacaccagct actgccccta cagccagtgc 900
gccttcaacg gcatcttcct gccacctctg cagggggatt tcggcgcctt cagcgccttc 960
tactccgtga tgaagttcct gaacctgacc agcgagaagg tgtcccagga aaaagtgaca 1020
gagatgatga agaagttctg cgcccagccc tgggaggaaa tcaagacctc ctacgctggc 1080
gtgaaagaga agtacctgag cgagtactgc ttcagcggca cctacatcct gagcctgctg 1140
ctgcagggct accacttcac cgccgatagc tgggagcaca tccacttcat cggcaagatt 1200
cagggcagcg acgccggctg gacactgggt tacatgctga atctgaccaa catgatcccc 1260
gccgagcagc ccctgagcac acctctgagc cacagcacc 1299
<210> 233
<211> 430
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 233
Ala Pro Thr Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly
1 5 10 15
Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys
20 25 30
Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu
35 40 45
Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val
50 55 60
Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu
65 70 75 80
Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala
85 90 95
Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp
100 105 110
Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp
115 120 125
Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly
130 135 140
Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln
145 150 155 160
Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr
165 170 175
Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln
180 185 190
Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu
195 200 205
Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile
210 215 220
Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly
225 230 235 240
Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr
245 250 255
Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly
260 265 270
Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn
275 280 285
Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu
290 295 300
Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Ser Val
305 310 315 320
Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val
325 330 335
Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys
340 345 350
Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe
355 360 365
Ser Gly Thr Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr His Phe Thr
370 375 380
Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser
385 390 395 400
Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile
405 410 415
Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425 430
<210> 234
<211> 1290
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 234
gcccctacca cccagaacaa ggccctgccc gagaacgtga agtacggcat cgtgctggat 60
gccggcagca gccacaccag cctgtacatc tacaagtggc ctgccgagaa agaaaacgac 120
accggcgtgg tgcatcaggt ggaagagtgc agagtgaagg gccctggcat cagcaagttc 180
gtgcagaaag tgaacgagat cggcatctac ctgaccgact gcatggaacg ggccatggaa 240
gtgatcccca gaagccagca ccaggaaacc cccgtgtatc tgggagccac cgccggcatg 300
agactgctga gaatggaaag cgaggaactg gccgaccggg tgctggacgt ggtggaaaga 360
agcctgagca actacccatt cgattttcaa ggcgccagaa tcatcaccgg ccaggaagaa 420
ggcgcctacg gctggatcac catcaactac ctgctgggca agttcagcca gaagaatcag 480
gaaaccttcg gcgccctgga cctgggcgga gcttctaccc aagtgacctt cgtgccccag 540
aatcagacca tcgagagccc cgacaacgcc ctgcagttcc ggctgtacgg caaggactac 600
aatgtgtaca cccacagctt tctgtgctac ggaaaggacc aggctctgtg gcagaagctg 660
gccaaggaca tccaggtggc cagcaacgag atcctgcggg acccttgctt ccaccccggc 720
tacaagaaag tcgtgaacgt gtccgacctg tacaagaccc cctgcaccaa gagattcgag 780
atgaccctgc ccttccagca gttcgagatc cagggcatcg gcaattacca gcagtgccac 840
cagagcatcc tggaactgtt caacaccagc tactgcccct acagccagtg cgccttcaac 900
ggcatcttcc tgccacctct gcagggggat ttcggcgcct tcagcgcctt ctactccgtg 960
atgaagttcc tgaacctgac cagcgagaag gtgtcccagg aaaaagtgac agagatgatg 1020
aagaagttct gcgcccagcc ctgggaggaa atcaagacct cctacgctgg cgtgaaagag 1080
aagtacctga gcgagtactg cttcagcggc acctacatcc tgagcctgct gcagcagggc 1140
taccacttca ccgccgatag ctgggagcac atccacttca tcggcaagat tcagggcagc 1200
gacgccggct ggacactggg ctacatgctg aatctgacca acatgatccc cgccgagcag 1260
cccctgagca cacctctgag ccacagcacc 1290
<210> 235
<211> 433
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 235
Ala Pro Thr Ser Ser Ser Thr Gln Asn Lys Ala Leu Pro Glu Asn Val
1 5 10 15
Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr
20 25 30
Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His
35 40 45
Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val
50 55 60
Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg
65 70 75 80
Ala Met Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr
85 90 95
Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu
100 105 110
Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr
115 120 125
Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly
130 135 140
Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln
145 150 155 160
Lys Asn Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr
165 170 175
Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn
180 185 190
Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His
195 200 205
Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala
210 215 220
Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe
225 230 235 240
His Pro Gly Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr
245 250 255
Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu
260 265 270
Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu
275 280 285
Leu Phe Asn Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly
290 295 300
Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe
305 310 315 320
Tyr Ser Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln
325 330 335
Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu
340 345 350
Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu
355 360 365
Tyr Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr
370 375 380
His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile
385 390 395 400
Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr
405 410 415
Asn Met Ile Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser
420 425 430
Thr
<210> 236
<211> 1299
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 236
gcccctacca gcagcagcac ccagaacaag gccctgcccg agaacgtgaa gtacggcatc 60
gtgctggatg ccggcagcag ccacaccagc ctgtacatct acaagtggcc tgccgagaaa 120
gaaaacgaca ccggcgtggt gcatcaggtg gaagagtgca gagtgaaggg ccctggcatc 180
agcaagttcg tgcagaaagt gaacgagatc ggcatctacc tgaccgactg catggaacgg 240
gccatggaag tgatccccag aagccagcac caggaaaccc ccgtgtatct gggagccacc 300
gccggcatga gactgctgag aatggaaagc gaggaactgg ccgaccgggt gctggacgtg 360
gtggaaagaa gcctgagcaa ctacccattc gattttcaag gcgccagaat catcaccggc 420
caggaagaag gcgcctacgg ctggatcacc atcaactacc tgctgggcaa gttcagccag 480
aagaatcagg aaaccttcgg cgccctggac ctgggcggag cttctaccca agtgaccttc 540
gtgccccaga atcagaccat cgagagcccc gacaacgccc tgcagttccg gctgtacggc 600
aaggactaca atgtgtacac ccacagcttt ctgtgctacg gaaaggacca ggctctgtgg 660
cagaagctgg ccaaggacat ccaggtggcc agcaacgaga tcctgcggga cccttgcttc 720
caccccggct acaagaaagt cgtgaacgtg tccgacctgt acaagacccc ctgcaccaag 780
agattcgaga tgaccctgcc cttccagcag ttcgagatcc agggcatcgg caattaccag 840
cagtgccacc agagcatcct ggaactgttc aacaccagct actgccccta cagccagtgc 900
gccttcaacg gcatcttcct gccacctctg cagggggatt tcggcgcctt cagcgccttc 960
tactccgtga tgaagttcct gaacctgacc agcgagaagg tgtcccagga aaaagtgaca 1020
gagatgatga agaagttctg cgcccagccc tgggaggaaa tcaagacctc ctacgctggc 1080
gtgaaagaga agtacctgag cgagtactgc ttcagcggca cctacatcct gagcctgctg 1140
cagcagggct accacttcac cgccgatagc tgggagcaca tccacttcat cggcaagatt 1200
cagggcagcg acgccggctg gacactgggc tacatgctga atctgaccaa catgatcccc 1260
gccgagcagc ccctgagcac acctctgagc cacagcacc 1299
<210> 237
<211> 430
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 237
Ala Pro Thr Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly
1 5 10 15
Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys
20 25 30
Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu
35 40 45
Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val
50 55 60
Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu
65 70 75 80
Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala
85 90 95
Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp
100 105 110
Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp
115 120 125
Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly
130 135 140
Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln
145 150 155 160
Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr
165 170 175
Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln
180 185 190
Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu
195 200 205
Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile
210 215 220
Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly
225 230 235 240
Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr
245 250 255
Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly
260 265 270
Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn
275 280 285
Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu
290 295 300
Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val
305 310 315 320
Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val
325 330 335
Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys
340 345 350
Thr Ser Tyr Ala Gly Val Asn Glu Lys Tyr Leu Ser Glu Phe Cys Phe
355 360 365
Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr
370 375 380
Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser
385 390 395 400
Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile
405 410 415
Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425 430
<210> 238
<211> 1290
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 238
gcccctacca cccagaacaa ggccctgccc gagaacgtga agtacggcat cgtgctggat 60
gccggcagca gccacaccag cctgtacatc tacaagtggc ctgccgagaa agaaaacgac 120
accggcgtgg tgcatcaggt ggaagagtgc agagtgaagg gccctggcat cagcaagttc 180
gtgcagaaag tgaacgagat cggcatctac ctgaccgact gcatggaacg ggccagggaa 240
gtgatcccca gaagccagca ccaggaaacc cccgtgtatc tgggagccac cgccggcatg 300
agactgctga gaatggaaag cgaggaactg gccgaccggg tgctggacgt ggtggaaaga 360
agcctgagca actacccatt cgattttcaa ggcgccagaa tcatcaccgg ccaggaagaa 420
ggcgcctacg gctggatcac catcaactac ctgctgggca agttcagcca gaagaatcag 480
gaaaccttcg gcgccctgga cctgggcgga gcttctaccc aagtgacctt cgtgccccag 540
aatcagacca tcgagagccc cgacaacgcc ctgcagttcc ggctgtacgg caaggactac 600
aatgtgtaca cccacagctt tctgtgctac ggaaaggacc aggctctgtg gcagaagctg 660
gccaaggaca tccaggtggc cagcaacgag atcctgcggg acccttgctt ccaccccggc 720
tacaagaaag tcgtgaacgt gtccgacctg tacaagaccc cctgcaccaa gagattcgag 780
atgaccctgc ccttccagca gttcgagatc cagggcatcg gcaattacca gcagtgccac 840
cagagcatcc tggaactgtt caacaccagc tactgcccct acagccagtg cgccttcaac 900
ggcatcttcc tgccacctct gcagggggat ttcggcgcct tcagcgcctt ctacttcgtg 960
atgaagttcc tgaacctgac cagcgagaag gtgtcccagg aaaaagtgac agagatgatg 1020
aagaagttct gcgcccaacc ctgggaggaa atcaagacct cctacgctgg cgtgaacgag 1080
aagtacctga gcgagttttg cttcagcggc acctacatcc tgagcctgct gctgcagggc 1140
taccacttca ccgccgatag ctgggagcac atccacttca tcggcaagat tcagggcagc 1200
gacgccggct ggacactggg ctacatgctg aatctgacca acatgatccc cgccgagcag 1260
cccctgagca cacctctgag ccacagcacc 1290
<210> 239
<211> 433
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 239
Ala Pro Thr Ser Ser Ser Thr Gln Asn Lys Ala Leu Pro Glu Asn Val
1 5 10 15
Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr
20 25 30
Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His
35 40 45
Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val
50 55 60
Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg
65 70 75 80
Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr
85 90 95
Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu
100 105 110
Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr
115 120 125
Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly
130 135 140
Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln
145 150 155 160
Lys Asn Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr
165 170 175
Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn
180 185 190
Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His
195 200 205
Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala
210 215 220
Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe
225 230 235 240
His Pro Gly Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr
245 250 255
Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu
260 265 270
Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu
275 280 285
Leu Phe Asn Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly
290 295 300
Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe
305 310 315 320
Tyr Phe Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln
325 330 335
Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu
340 345 350
Glu Ile Lys Thr Ser Tyr Ala Gly Val Asn Glu Lys Tyr Leu Ser Glu
355 360 365
Phe Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr
370 375 380
His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile
385 390 395 400
Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr
405 410 415
Asn Met Ile Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser
420 425 430
Thr
<210> 240
<211> 1299
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 240
gcccctacca gcagcagcac ccagaacaag gccctgcccg agaacgtgaa gtacggcatc 60
gtgctggatg ccggcagcag ccacaccagc ctgtacatct acaagtggcc tgccgagaaa 120
gaaaacgaca ccggcgtggt gcatcaggtg gaagagtgca gagtgaaggg ccctggcatc 180
agcaagttcg tgcagaaagt gaacgagatc ggcatctacc tgaccgactg catggaacgg 240
gccagggaag tgatccccag aagccagcac caggaaaccc ccgtgtatct gggagccacc 300
gccggcatga gactgctgag aatggaaagc gaggaactgg ccgaccgggt gctggacgtg 360
gtggaaagaa gcctgagcaa ctacccattc gattttcaag gcgccagaat catcaccggc 420
caggaagaag gcgcctacgg ctggatcacc atcaactacc tgctgggcaa gttcagccag 480
aagaatcagg aaaccttcgg cgccctggac ctgggcggag cttctaccca agtgaccttc 540
gtgccccaga atcagaccat cgagagcccc gacaacgccc tgcagttccg gctgtacggc 600
aaggactaca atgtgtacac ccacagcttt ctgtgctacg gaaaggacca ggctctgtgg 660
cagaagctgg ccaaggacat ccaggtggcc agcaacgaga tcctgcggga cccttgcttc 720
caccccggct acaagaaagt cgtgaacgtg tccgacctgt acaagacccc ctgcaccaag 780
agattcgaga tgaccctgcc cttccagcag ttcgagatcc agggcatcgg caattaccag 840
cagtgccacc agagcatcct ggaactgttc aacaccagct actgccccta cagccagtgc 900
gccttcaacg gcatcttcct gccacctctg cagggggatt tcggcgcctt cagcgccttc 960
tacttcgtga tgaagttcct gaacctgacc agcgagaagg tgtcccagga aaaagtgaca 1020
gagatgatga agaagttctg cgcccaaccc tgggaggaaa tcaagacctc ctacgctggc 1080
gtgaacgaga agtacctgag cgagttttgc ttcagcggca cctacatcct gagcctgctg 1140
ctgcagggct accacttcac cgccgatagc tgggagcaca tccacttcat cggcaagatt 1200
cagggcagcg acgccggctg gacactgggc tacatgctga atctgaccaa catgatcccc 1260
gccgagcagc ccctgagcac acctctgagc cacagcacc 1299
<210> 241
<211> 442
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 241
Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Thr Ser Ser Thr
1 5 10 15
Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu Asp
20 25 30
Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala Glu
35 40 45
Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg Val
50 55 60
Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile Gly
65 70 75 80
Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro Arg
85 90 95
Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly Met
100 105 110
Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu Asp
115 120 125
Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly Ala
130 135 140
Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr Ile
145 150 155 160
Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe Gly
165 170 175
Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro Gln
180 185 190
Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu Tyr
195 200 205
Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly Lys
210 215 220
Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala Ser
225 230 235 240
Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys Val
245 250 255
Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe Glu
260 265 270
Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn Tyr
275 280 285
Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr Cys
290 295 300
Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu Gln
305 310 315 320
Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe Leu
325 330 335
Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met Met
340 345 350
Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr Ala
355 360 365
Gly Val Asn Glu Lys Tyr Leu Ser Glu Phe Cys Phe Ser Gly Thr Tyr
370 375 380
Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser Trp
385 390 395 400
Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly Trp
405 410 415
Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu Gln
420 425 430
Pro Leu Ser Thr Pro Leu Ser His Ser Thr
435 440
<210> 242
<211> 1326
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 242
gcccctacca gcagcagcac caagaaaacc cagctgacca gcagcaccca gaacaaggcc 60
ctgcccgaga acgtgaagta cggcatcgtg ctggatgccg gcagcagcca caccagcctg 120
tacatctaca agtggcctgc cgagaaagaa aacgacaccg gcgtggtgca tcaggtggaa 180
gagtgcagag tgaagggccc tggcatcagc aagttcgtgc agaaagtgaa cgagatcggc 240
atctacctga ccgactgcat ggaacgggcc agggaagtga tccccagaag ccagcaccag 300
gaaacccccg tgtatctggg agccaccgcc ggcatgagac tgctgagaat ggaaagcgag 360
gaactggccg accgggtgct ggacgtggtg gaaagaagcc tgagcaacta cccattcgat 420
tttcaaggcg ccagaatcat caccggccag gaagaaggcg cctacggctg gatcaccatc 480
aactacctgc tgggcaagtt cagccagaag aatcaggaaa ccttcggcgc cctggacctg 540
ggcggagctt ctacccaagt gaccttcgtg ccccagaatc agaccatcga gagccccgac 600
aacgccctgc agttccggct gtacggcaag gactacaatg tgtacaccca cagctttctg 660
tgctacggaa aggaccaggc tctgtggcag aagctggcca aggacatcca ggtggccagc 720
aacgagatcc tgcgggaccc ttgcttccac cccggctaca agaaagtcgt gaacgtgtcc 780
gacctgtaca agaccccctg caccaagaga ttcgagatga ccctgccctt ccagcagttc 840
gagatccagg gcatcggcaa ttaccagcag tgccaccaga gcatcctgga actgttcaac 900
accagctact gcccctacag ccagtgcgcc ttcaacggca tcttcctgcc acctctgcag 960
ggggatttcg gcgccttcag cgccttctac ttcgtgatga agttcctgaa cctgaccagc 1020
gagaaggtgt cccaggaaaa agtgacagag atgatgaaga agttctgcgc ccaaccctgg 1080
gaggaaatca agacctccta cgctggcgtg aacgagaagt acctgagcga gttttgcttc 1140
agcggcacct acatcctgag cctgctgctg cagggctacc acttcaccgc cgatagctgg 1200
gagcacatcc acttcatcgg caagattcag ggcagcgacg ccggctggac actgggctac 1260
atgctgaatc tgaccaacat gatccccgcc gagcagcccc tgagcacacc tctgagccac 1320
agcacc 1326
<210> 243
<211> 430
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 243
Ala Pro Thr Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly
1 5 10 15
Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys
20 25 30
Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu
35 40 45
Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val
50 55 60
Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu
65 70 75 80
Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala
85 90 95
Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp
100 105 110
Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp
115 120 125
Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly
130 135 140
Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln
145 150 155 160
Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr
165 170 175
Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln
180 185 190
Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu
195 200 205
Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile
210 215 220
Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly
225 230 235 240
Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr
245 250 255
Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly
260 265 270
Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn
275 280 285
Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu
290 295 300
Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val
305 310 315 320
Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val
325 330 335
Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys
340 345 350
Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe
355 360 365
Ser Gly Thr Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr His Phe Thr
370 375 380
Ala Asp Ser Trp Glu Asp Ile His Phe Ile Gly Lys Ile Gln Gly Ser
385 390 395 400
Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile
405 410 415
Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr
420 425 430
<210> 244
<211> 1290
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 244
gcccctacca cccagaacaa ggccctgccc gagaacgtga agtacggcat cgtgctggat 60
gccggcagca gccacaccag cctgtacatc tacaagtggc ctgccgagaa agaaaacgac 120
accggcgtgg tgcatcaggt ggaagagtgc agagtgaagg gccctggcat cagcaagttc 180
gtgcagaaag tgaacgagat cggcatctac ctgaccgact gcatggaacg ggccagggaa 240
gtgatcccca gaagccagca ccaggaaacc cccgtgtatc tgggagccac cgccggcatg 300
agactgctga gaatggaaag cgaggaactg gccgaccggg tgctggacgt ggtggaaaga 360
agcctgagca actacccatt cgattttcaa ggcgccagaa tcatcaccgg ccaggaagaa 420
ggcgcctacg gctggatcac catcaactac ctgctgggca agttcagcca gaagaatcag 480
gaaaccttcg gcgccctgga cctgggcgga gcttctaccc aagtgacctt cgtgccccag 540
aatcagacca tcgagagccc cgacaacgcc ctgcagttcc ggctgtacgg caaggactac 600
aatgtgtaca cccacagctt tctgtgctac ggaaaggacc aggctctgtg gcagaagctg 660
gccaaggaca tccaggtggc cagcaacgag atcctgcggg acccttgctt ccaccccggc 720
tacaagaaag tcgtgaacgt gtccgacctg tacaagaccc cctgcaccaa gagattcgag 780
atgaccctgc ccttccagca gttcgagatc cagggcatcg gcaattacca gcagtgccac 840
cagagcatcc tggaactgtt caacaccagc tactgcccct acagccagtg cgccttcaac 900
ggcatcttcc tgccacctct gcagggggat ttcggcgcct tcagcgcctt ctacttcgtg 960
atgaagttcc tgaacctgac cagcgagaag gtgtcccagg aaaaagtgac agagatgatg 1020
aagaagttct gcgcccagcc ctgggaggaa atcaagacct cctacgctgg cgtgaaagag 1080
aagtacctga gcgagtactg cttcagcggc acctacatcc tgagcctgct gcagcagggc 1140
taccacttca ccgccgatag ctgggaggac atccacttca tcggcaagat tcagggcagc 1200
gacgccggct ggacactggg ctacatgctg aatctgacca acatgatccc cgccgagcag 1260
cccctgagca cacctctgag ccacagcacc 1290
<210> 245
<211> 433
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polypeptide"
<400> 245
Ala Pro Thr Ser Ser Ser Thr Gln Asn Lys Ala Leu Pro Glu Asn Val
1 5 10 15
Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr
20 25 30
Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His
35 40 45
Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val
50 55 60
Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg
65 70 75 80
Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr
85 90 95
Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu
100 105 110
Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr
115 120 125
Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly
130 135 140
Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln
145 150 155 160
Lys Asn Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr
165 170 175
Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn
180 185 190
Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His
195 200 205
Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala
210 215 220
Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe
225 230 235 240
His Pro Gly Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr
245 250 255
Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu
260 265 270
Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu
275 280 285
Leu Phe Asn Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly
290 295 300
Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe
305 310 315 320
Tyr Phe Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln
325 330 335
Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu
340 345 350
Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu
355 360 365
Tyr Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr
370 375 380
His Phe Thr Ala Asp Ser Trp Glu Asp Ile His Phe Ile Gly Lys Ile
385 390 395 400
Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr
405 410 415
Asn Met Ile Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser
420 425 430
Thr
<210> 246
<211> 1299
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
polynucleotide"
<400> 246
gcccctacca gcagcagcac ccagaacaag gccctgcccg agaacgtgaa gtacggcatc 60
gtgctggatg ccggcagcag ccacaccagc ctgtacatct acaagtggcc tgccgagaaa 120
gaaaacgaca ccggcgtggt gcatcaggtg gaagagtgca gagtgaaggg ccctggcatc 180
agcaagttcg tgcagaaagt gaacgagatc ggcatctacc tgaccgactg catggaacgg 240
gccagggaag tgatccccag aagccagcac caggaaaccc ccgtgtatct gggagccacc 300
gccggcatga gactgctgag aatggaaagc gaggaactgg ccgaccgggt gctggacgtg 360
gtggaaagaa gcctgagcaa ctacccattc gattttcaag gcgccagaat catcaccggc 420
caggaagaag gcgcctacgg ctggatcacc atcaactacc tgctgggcaa gttcagccag 480
aagaatcagg aaaccttcgg cgccctggac ctgggcggag cttctaccca agtgaccttc 540
gtgccccaga atcagaccat cgagagcccc gacaacgccc tgcagttccg gctgtacggc 600
aaggactaca atgtgtacac ccacagcttt ctgtgctacg gaaaggacca ggctctgtgg 660
cagaagctgg ccaaggacat ccaggtggcc agcaacgaga tcctgcggga cccttgcttc 720
caccccggct acaagaaagt cgtgaacgtg tccgacctgt acaagacccc ctgcaccaag 780
agattcgaga tgaccctgcc cttccagcag ttcgagatcc agggcatcgg caattaccag 840
cagtgccacc agagcatcct ggaactgttc aacaccagct actgccccta cagccagtgc 900
gccttcaacg gcatcttcct gccacctctg cagggggatt tcggcgcctt cagcgccttc 960
tacttcgtga tgaagttcct gaacctgacc agcgagaagg tgtcccagga aaaagtgaca 1020
gagatgatga agaagttctg cgcccagccc tgggaggaaa tcaagacctc ctacgctggc 1080
gtgaaagaga agtacctgag cgagtactgc ttcagcggca cctacatcct gagcctgctg 1140
cagcagggct accacttcac cgccgatagc tgggaggaca tccacttcat cggcaagatt 1200
cagggcagcg acgccggctg gacactgggc tacatgctga atctgaccaa catgatcccc 1260
gccgagcagc ccctgagcac acctctgagc cacagcacc 1299
<210> 247
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 247
Glu Phe Arg His Asp Ser
1 5
<210> 248
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 248
gaattccggc acgacagc 18
<210> 249
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
6xHis tag"
<400> 249
His His His His His His
1 5
<210> 250
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
<400> 250
catcatcatc atcatcac 18
<210> 251
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 251
Gly Gly Gly Gly Ser
1 5
<210> 252
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 252
Val Lys Glu Lys Tyr Leu Ser Glu
1 5
<210> 253
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
peptide"
<400> 253
Gln Glu Arg Trp Leu Arg Asp
1 5
Claims (28)
- N 말단 결실, C 말단 결실 및 중심 변형으로 구성된 목록으로부터 선택된 적어도 2종의 변형이 있는 가용화된 인간 아피라제.
- 제1항에 있어서, N 말단 결실, C 말단 결실 및 중심 변형이 있는 가용화된 인간 아피라제.
- 제1항 또는 제2항에 있어서,
a) N 말단 결실은 30 내지 50개의 아미노산 길이이고,
b) C 말단 결실은 20 내지 40개의 아미노산 길이이고,
c) 중심 변형은 결실 및/또는 점 돌연변이를 포함하는 것인, 가용화된 인간 아피라제. - 제1항 내지 제3항 중 어느 한 항에 있어서, 중심 변형은 10 내지 15개의 연속적인 아미노산의 결실을 포함하는 것인, 가용화된 인간 아피라제.
- 제4항에 있어서, 중심 변형은 서열번호 1에 따른 야생형 CD39 서열과 관련하여 아미노산 번호 193 내지 204의 결실인 것인, 가용화된 인간 아피라제.
- 제1항 내지 제5항 중 어느 한 항에 있어서, 중심 변형은 K71E, N73Q, V95A, G102D, Y104S, T106S, R113M, L149M, V151A, E173D, T229A, L254M, K258R, W263R, E276D, N292Q, R304G, I319T, N327Q, A362N, F365S, N371Q, K405N, Y412F, L424Q, H436D, I437N, F439S, G441D, N457Q, P463S, 및 S469R로 구성된 군으로부터 선택된, 서열번호 1에 따른 야생형 CD39 서열과 관련하여 1, 2, 3, 4, 또는 5개의 점 돌연변이를 포함하는, 점 돌연변이를 포함하는 것인, 가용화된 인간 아피라제.
- 제1항 내지 제6항 중 어느 한 항에 있어서, 서열번호 4, 서열번호 6, 서열번호 32, 서열번호 54, 서열번호 56, 서열번호 70, 서열번호 76, 및 서열번호 78로 구성된 군으로부터 선택된 서열을 포함하는, 가용화된 인간 아피라제.
- 제1항 내지 제7항 중 어느 한 항에 있어서, 서열번호 131, 서열번호 133, 서열번호 135, 서열번호 137, 서열번호 139 및 서열번호 141로 구성된 군으로부터 선택된 서열을 포함하는, 가용화된 인간 아피라제.
- 제8항에 있어서, 서열번호 213, 서열번호 227, 서열번호 219, 서열번호 225, 서열번호 217, 서열번호 209, 서열번호 221, 서열번호 72, 서열번호 215, 서열번호 223, 서열번호 211, 서열번호 58 및 서열번호 229로 구성된 군으로부터 선택된 서열을 포함하거나 이로 구성된, 가용화된 인간 아피라제.
- 제9항에 있어서, 서열번호 58, 서열번호 72 및 서열번호 229로 구성된 군으로부터 선택된 서열로 구성된, 가용화된 인간 아피라제.
- 제1항 내지 제10항 중 어느 한 항의 아피라제의 치료 유효 용량 및 1종 이상의 제약상 허용 가능한 담체를 포함하는 제약 조성물.
- 제11항에 있어서, 1종 이상의 추가 활성 성분을 더 포함하는 제약 조성물.
- 의약으로서 사용하기 위한 제1항 내지 제10항의 단리된 아피라제.
- 조직 손상의 치료에 사용하기 위한 제1항 내지 제10항의 단리된 아피라제.
- 제14항에 있어서, 조직 손상은 급성 뇌 손상(뇌졸중); 급성 다기관 부전; 신장 또는 기타 고형 장기 이식 후 지연 이식편 기능; 화상 손상; 방사선 손상; 외상 및/또는 저산소증으로 인한 급성 손상, 예컨대 급성 호흡 곤란 증후군(ARDS) 또는 폐 손상; 급성 신장 손상, 예컨대 흉부 수술(예를 들어, 대동맥 판막 교체, 관상 동맥 우회 수술) 또한 패혈증 또는 횡문근 융해증 또는 항생제 또는 기타 약물의 독성 효과에 따른 급성 신장 손상; 급성 심근 손상인, 사용하기 위한 단리된 아피라제.
- 심장 수술 관련 급성 신장 손상의 치료에 사용하기 위한 제1항 내지 제10항의 단리된 아피라제.
- 지연 이식편 기능(DGF), 급성 호흡 곤란 증후군(ARDS), 급성 심근 경색(AMI), 외상성 뇌 손상(TBI)/급성 허혈 뇌졸중(AIS), 허혈-재관류 손상(IRI), 또는 종종 다기관 부전(MOF)으로 지칭되는 이들의 조합의 치료에 사용하기 위한 제1항 내지 제10항의 단리된 아피라제.
- 패혈증 관련 급성 신장 손상의 치료에 사용하기 위한 제1항 내지 제10항의 단리된 아피라제.
- 인간 대상체의 조직 손상의 치료 방법으로서, 상기 대상체에게 가용화된 인간 아피라제의 치료 유효 용량을 투여하는 단계를 포함하는 방법.
- 제19항에 있어서, 가용화된 인간 아피라제는 제1항 내지 제10항의 아피라제인 것인, 방법.
- 제19항 또는 제20항에 있어서, 조직 손상은 급성 뇌 손상(뇌졸중); 급성 다기관 부전; 신장 또는 기타 고형 장기 이식 후 지연 이식편 기능; 화상 손상; 방사선 손상; 외상 및/또는 저산소증으로 인한 급성 손상, 예컨대 급성 호흡 곤란 증후군(ARDS) 또는 폐 손상; 급성 신장 손상, 예컨대 흉부 수술(예를 들어, 대동맥 판막 교체, 관상 동맥 우회 수술) 또한 패혈증 또는 횡문근 융해증 또는 항생제 또는 기타 약물의 독성 효과에 따른 급성 신장 손상; 급성 심근 손상인, 방법.
- 심장 수술 관련 급성 신장 손상의 치료 방법으로서, 이러한 치료를 필요로 하는 대상체에게 가용화된 인간 아피라제의 치료 유효 용량을 투여하는 단계를 포함하는 방법.
- 지연 이식편 기능(DGF), 급성 호흡 곤란 증후군(ARDS), 급성 심근 경색(AMI), 외상성 뇌 손상(TBI)/급성 허혈 뇌졸중(AIS), 허혈-재관류 손상(IRI), 또는 종종 다기관 부전(MOF)으로 지칭되는 이들의 조합의 치료 방법으로서, 이러한 치료를 필요로 하는 대상체에게 가용화된 인간 아피라제의 치료 유효 용량을 투여하는 단계를 포함하는 방법.
- 패혈증 관련 급성 신장 손상의 치료 방법으로서, 이러한 치료를 필요로 하는 대상체에게 가용화된 인간 아피라제의 치료 유효 용량을 투여하는 단계를 포함하는 방법.
- 제1항 내지 제10항의 임의의 아피라제를 암호화하는 단리된 핵산 분자.
- 제25항에 따른 1개 이상의 핵산 서열을 포함하는 클로닝 또는 발현 벡터로서, 제1항 내지 제10항의 단리된 아피라제의 재조합 생산에 적합한 것인, 클로닝 또는 발현 벡터.
- 제26항에 따른 1개 이상의 클로닝 또는 발현 벡터를 포함하는 숙주 세포.
- 제1항 내지 제10항 중 어느 한 항의 아피라제의 생산 공정으로서, 제27항에 따른 숙주 세포를 배양하는 단계, 정제하는 단계, 및 상기 아피라제를 회수하는 단계를 포함하는 공정.
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| PCT/IB2019/056117 WO2020016804A1 (en) | 2018-07-18 | 2019-07-17 | Solubilized apyrases, methods and use |
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| TW202404627A (zh) | 2022-07-29 | 2024-02-01 | 瑞士商諾華公司 | 使用cd39、重組cd39用於急性器官損傷的治療 |
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| US20020002277A1 (en) * | 1998-10-16 | 2002-01-03 | Maliszewski Charles Richard | Inhibitors of platelet activation and recruitment |
| US6867177B2 (en) | 1999-08-13 | 2005-03-15 | The Trustees Of Columbia University In The City Of New York | CD39/ECTO-adpase as a treatment for thrombotic and ischemic disorders |
| US7247300B1 (en) | 2002-11-07 | 2007-07-24 | Apt Therapeutics, Inc. | Therapeutic use of soluble CD39L3 |
| US8551774B2 (en) | 2005-03-17 | 2013-10-08 | National Research Council Of Canada | Expression vectors containing a truncated epstein barr nuclear antigen 1 lacking the Gly-Gly-Ala domain for enhanced transient gene expression |
| US8535662B2 (en) * | 2010-01-13 | 2013-09-17 | Apt Therapeutics, Inc. | Apyrase therapy for bleeding conditions |
| PL3083677T3 (pl) | 2013-12-20 | 2020-03-31 | Novartis Ag | Nowe komórki eukariotyczne i sposoby rekombinowanej ekspresji produktu będącego przedmiotem zainteresowania |
| AU2014369175B2 (en) | 2013-12-20 | 2017-03-02 | Novartis Ag | Novel eukaryotic cells and methods for recombinantly expressing a product of interest |
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| CN112424346A (zh) | 2021-02-26 |
| JP2021529550A (ja) | 2021-11-04 |
| UY38299A (es) | 2020-02-28 |
| MA53177A (fr) | 2021-05-26 |
| EP3824079A1 (en) | 2021-05-26 |
| JP7425784B2 (ja) | 2024-01-31 |
| PH12021550122A1 (en) | 2021-09-27 |
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| ECSP21002804A (es) | 2021-04-29 |
| AR115790A1 (es) | 2021-02-24 |
| AU2019306821B2 (en) | 2022-09-29 |
| AU2019306821A1 (en) | 2020-12-24 |
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| SG11202011776RA (en) | 2021-02-25 |
| MX2021000542A (es) | 2021-03-29 |
| BR112021000586A2 (pt) | 2021-04-06 |
| CR20210021A (es) | 2021-03-23 |
| CU20210008A7 (es) | 2021-08-06 |
| WO2020016804A1 (en) | 2020-01-23 |
| IL280191A (en) | 2021-03-01 |
| CA3103684A1 (en) | 2020-01-23 |
| CO2021000210A2 (es) | 2021-01-18 |
| JOP20210008A1 (ar) | 2021-01-12 |
| ZA202007187B (en) | 2022-06-29 |
| US20220356455A1 (en) | 2022-11-10 |
| PE20210185A1 (es) | 2021-02-02 |
| EA202190057A1 (ru) | 2021-08-24 |
| CL2021000129A1 (es) | 2021-08-20 |
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