KR20100105630A - 유인원 아과 ｃ 아데노바이러스 ｓａｄｖ-40, -31, 및 -34 및 그것의 사용 - Google Patents
유인원 아과 ｃ 아데노바이러스 ｓａｄｖ-40, -31, 및 -34 및 그것의 사용 Download PDFInfo
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Abstract
재조합 벡터는 조절 서열의 제어 하에서 유인원 아데노바이러스 SAdV-40, SAdV-31 또는 SAdV-34 서열 및 이종성 유전자를 포함한다. 유인원 아데노바이러스 SAdV-40, SAdV-31 또는 SAdV-34 유전자를 발현시키는 셀 라인이 또한 개시된다. 벡터 및 셀 라인을 사용하는 방법이 제공된다.
Description
아데노바이러스는 약 36 킬로베이스(kb)의 게놈 크기를 가지는 이중-나선 DNA 바이러스이며, 이는 다양한 표적 조직에서 고성능 유전자 전이 및 거대 이식 유전자 수용력을 달성하는 그것의 능력에 기인하여 유전자 전달 용도를 위해 널리 사용되었다. 전통적으로 아데노바이러스의 E1 유전자는 결실되고, 선택 프로모터, 관심 유전자의 cDNA 서열 및 폴리 A 시그널로 구성되는 이식 유전자 카세트로 대체되는데, 이는 복제 결함 재조합 바이러스를 초래한다.
아데노바이러스는 3개의 주요 단백질, 헥손(II), 펜톤 염기(III) 및 혹모양 섬유(IV)와 다수의 다른 부수적 단백질, VI, VIII, IX, IIIa 및 IVa2로 구성되는 다면체형의 캡시드를 가지는 특징적인 형태를 가진다[W.C. Russell, J. Gen Virol., 81 :2573-2604 (2000년 11월)]. 바이러스 게놈은 역위 말단 반복(ITR)을 가지는 5' 말단에 공유적으로 부착되는 말단 단백질을 가지는 선형의, 이중-나선 DNA이다. 바이러스 DNA는 고염기성 단백질 VII 및 소펩티드 pX(이전에 뮤로 언급됨)와 상세하게 관련된다. 다른 단백질 V는 이 DNA-단백질 복합체와 함께 패키징되고 단백질 VI를 통해 캡시드에 구조적 연결을 제공한다. 바이러스는 또한 성숙한 감염 바이러스를 만들기 위해 일부 구조적 단백질을 처리하는데 필요한 바이러스-암호화된 프로테아제를 함유한다.
분류체계는 인간, 유인원, 소, 말, 돼지, 양, 개 및 주머니쥐 아데노바이러스를 포함하는 포유류아데노바이러스 과를 위해 개발되었다. 이 분류체계는 적혈구를 교착시키기 위해 과 내의 아데노바이러스 서열의 다른 능력에 기초하여 개발되었다. 결과는 현재 아군 A, B, C, D, E 및 F로서 언급되는 6개의 아군이었다. B.N Fields et al, (Lippincott Raven Publishers, Philadelphia, 1996)에 의해 편집된 FIELD'S VIROLOGY, 6th Ed.의 T. Shenk et al , Adenovihdae : The Viruses and their Replication", Ch. 67, p. 111-2112 참조.
재조합 아데노바이러스는 숙주 세포에 이종성 분자의 전달에 대해 설명되었다. 두 침팬지 아데노바이러스의 게놈을 설명하는 미국 특허 6,083,716 참조. 유인원 아데노바이러스, C5, C6 및 C7은 백신 벡터로서 유용한 미국 특허 7,247,472호에서 설명되었다. 다른 침팬지 아데노바이러스는 아데노바이러스 백신 담체를 제조하는데 유용한 WO 2005/1071093에서 설명되었다.
당업계에서 필요로 되는 것은 표적에 분자를 효과적으로 전달하고 모집단에서 선택된 아데노바이러스 항원형에 기존 면역의 효과를 최소화하는 벡터이다.
아과 C 내의 3개의 신규한 유인원 아데노바이러스의 분리된 핵산 서열 및 아미노산 서열 및 이들 서열을 함유하는 벡터가 본원에서 제공된다. 또한 본 발명의 벡터 및 세포를 사용하는 다수의 방법이 제공된다. 이들 아데노바이러스는 SAdV-40, SAdV-31 및 SAdV-34를 포함한다.
본원에 설명되는 방법은 본 발명의 벡터를 투여함으로써 포유동물 환자에 하나 이상의 선택된 이종성 유전자(들)을 전달하는 단계를 수반한다. 백신접종을 위해 본원에서 기술되는 조성물의 사용은 보호성 면역 반응의 유발을 위한 선택된 항원의 제시를 허용한다. 이들 유인원 아데노바이러스에 기초한 벡터는 또한 시험관내 이종성 유전자 생성물을 만들기 위해 사용될 수 있다. 이러한 유전자 생성물은 그 자체가 본원에 설명되는 것과 같은 다양한 목적을 위해 유용하다.
본 발명의 이들 및 다른 구체예 및 이점은 하기에서 더욱 상세하게 기술된다.
모두 침팬지 배설물로부터 분리된 유인원 아데노바이러스 40, SAdV-31 및SAdV-34로부터의 신규 핵산 및 아미노산 서열이 제공된다.
또한 재조합 단백질 또는 단편 또는 다른 시약의 시험관 내 생성에서 사용을 위한 이들 벡터를 생성하기 위한 신규 아데노바이러스 벡터 및 팩키징 셀 라인이 제공된다. 더 나아가 치료적 또는 백신 목적을 위한 이종성 분자를 전달하는데 사용을 위한 조성물이 제공된다. 이러한 치료적 또는 백신 조성물은 삽입된 이종성 분자를 전달하는 아데노바이러스 벡터를 함유한다. 게다가, 신규의 SAdV 서열은 재조합 아데노-관련 바이러스(AAV) 벡터의 생성을 위해 필요로 되는 필수적인 헬퍼 기능을 제공하는데 유용하다. 따라서, 이러한 생성 방법에서 이들 서열을 사용하는 헬퍼 구조체, 방법 및 셀 라인이 제공된다.
이들 바이러스가 아군 C로부터 유래하기 때문에, 이들 바이러스의 캡시드(선택적으로 무결함 또는 재조합 바이러스 입자 또는 중공 캡시드)는 면역조절 효과를 유발하는 방법에 유용하거나 또는 피험자에 아데노바이러스 아군 C 캡시드를 전달함으로써 면역반응이 향상된다. SAdV-40, SAdV-31 또는 SAdV-34 캡시드는 단독으로 또는 그것에서 면역반응을 향상시키기 위한 활성 약제와 함께 요법과 조합하여 전달될 수 있다. 다른 양태에서, SAdV-40, SAdV-31 또는 SAdV-34 캡시드를 피험자에 전달하는 단계를 포함하는 그것이 필요한 피험자에서 인터페론 알파 생성을 유발하는 방법이 제공된다. 또 다른 양태에서, 배양물에서 하나 이상의 사이토카인을 생성하는 방법이 제공된다. 이 방법은 특히 알파 인터페론을 포함하는 사이토카인/케모킨을 생성하기에 적당한 조건하에서 수지상 세포 및 본원에 설명되는 SAdV 캡시드를 함유하는 배양물을 배양하는 단계를 수반한다.
핵산 또는 그것의 단편을 말할 때, 용어 "실질적인 상동성" 또는 "실질적인 유사성"은, 다른 핵산(또는 그것의 상보적 가닥)과 함께 적절한 뉴클레오티드 삽입 또는 결실에 의해 최상으로 배열될 때, 배열된 서열의 적어도 약 95 내지 99%로 뉴클레오티드 서열 동일성이 있음을 나타낸다.
아미노산 또는 그것의 단편을 말할 때, 용어 "실질적인 상동성" 또는 "실질적인 유사성"은, 다른 아미노산(또는 그것의 상보적 가닥)과 함께 적절한 아미노산 삽입 또는 결실에 의해 최상으로 배열될 때, 배열된 서열의 적어도 약 95 내지 99%로 아미노산 서열 동일성이 있음을 나타낸다. 바람직하게는, 상동성은 길이에 있어서 적어도 8개의 아미노산, 또는 더 바람직하게는 적어도 15개의 아미노산인 전장 서열, 또는 그것의 단백질, 또는 그것의 단편에 있다. 적절한 단편의 예는 본원에서 기술된다.
핵산 서열에 있어서 용어 "백분율 서열 동일성" 또는 "동일한"은 최대 대응에 대해 배열될 때 동일한 두 서열의 잔기를 말한다. 한 서열과 다른 서열을 배열하는데 갭이 필요로 될 때, 스코어링의 정도는 갭에 대한 불이익 없이 더 긴 서열에 대해 계산된다. 폴리뉴클레오티드 또는 암호화된 폴리펩티드의 기능성을 보존하는 서열은 이에 의해 더욱 밀접하게 동일하다. 서열 길이 동일성 비교는 게놈의 전장(예를 들어, 약 36 kbp), 유전자, 단백질, 서브유닛, 또는 효소의 오픈리딩프레임의 전장[예를 들어, 아데노바이러스 코딩 영역을 제공하는 표]에 걸쳐 있을 수 있고, 또는 적어도 약 500 내지 5000개의 뉴클레오티드의 단편이 요망된다. 그러나, 예를 들어, 적어도 약 9개의 뉴클레오티드, 보통 적어도 약 20 내지 24개의 뉴클레오티드, 적어도 약 28 내지 32개의 뉴클레오티드, 적어도 약 36개 또는 그 이상의 뉴클레오티드를 가지는 더 작은 단편들 사이의 동일성이 또한 요망될 수 있다. 유사하게, "백분율 서열 동일성"은 단백질, 또는 그것의 단편의 전장에 걸쳐서 아미노산 서열에 대해 용이하게 결정될 수 있다. 적절하게, 단편은 길이에 있어서 적어도 8개의 아미노산이며, 약 700개까지의 아미노산이 있을 수 있다. 적절한 단편의 예는 본원에서 기술된다.
동일성은 디폴트 세팅에서 정의되는 바와 같은 이러한 알고리즘 및 컴퓨터 프로그램을 사용하여 용이하게 결정된다. 바람직하게는, 이러한 동일성은 단백질, 효소, 서브유닛의 전장에 걸쳐, 또는 길이에 있어서 적어도 약 8개의 단편에 걸쳐서 있다. 그러나, 동일성은 더 짧은 영역에 기초할 수 있으며, 동일성 유전자 생성물이 배치되는 사용에 적합하다.
본원에서 설명되는 바와 같은, 배열은 인터넷의 웹 서버를 통해 접근가능한 "Clustal W"와 같은 다양한 일반 공중에게 또는 상업적으로 이용가능한 Multiple Sequence Alignment 프로그램을 사용하여 수행된다. 또 다르게는, 벡터 NTI® 유틸리티[InVitrogen]가 또한 사용된다. 상기 기술된 프로그램에 함유된 것들을 포함하는 뉴클레오티드 서열 동일성을 측정하는데 사용될 수 있는 당업계에 공지된 다수의 알고리즘이 있다. 다른 예에서, 폴리뉴클레오티드 서열은 Fasta, GCG Version 6.1의 프로그램을 사용하여 비교될 수 있다. Fasta는 질의와 검색 서열 사이의 최상의 중첩 영역의 배열 및 백분율 서열 동일성을 제공한다. 예를 들어, 핵산 서열 사이의 백분율 서열 동일성은 참고로써 본원에 포함되는 GCG Version 6.1에서 제공되는 바와 같은 Fasta와 그것의 디폴트 매개변수(워드 크기 6 및 스코어링 매트릭스에 대한 NOPAM 인자)를 사용하여 결정될 수 있다. 유사하게 프로그램은 아미노산 배열을 수행하기 위해 이용가능하다. 일반적으로, 당업자가 필요하다면 이들 세팅을 변경할 수 있지만, 이들 프로그램은 디폴트 세팅에서 사용된다. 또 다르게는, 당업자는 기준 알고리즘 및 프로그램에 의해 제공되는 동일성 또는 배열의 최소한의 수준을 제공하는 다른 알고리즘 또는 컴퓨터 프로그램을 이용할 수 있다.
폴리뉴클레오티드에 사용되는 "재조합"은, 폴리뉴클레오티드가 클로닝, 제한 또는 연결 단계, 및 천연에서 발견되는 폴리뉴클레오티드와 별개인 구조체를 초래하는 다른 과정의 다양한 조합의 생성물이라는 것을 의미한다. 재조합 바이러스는 재조합 폴리뉴클레오티드를 포함하는 바이러스 입자이다. 용어는 각각 본래의 폴리뉴클레오티드 구조체의 복제물 및 본래의 바이러스 구조체의 자손을 포함한다.
"이종성"은 비교되는 독립체의 나머지로부터 유전자형으로 완전한 독립체에서 유래됨을 의미한다. 예를 들어, 플라스미드에 유전공학 기술에 의해 도입된 폴리뉴클레오티드 또는 다른 종으로부터 유래된 벡터는 이종성 폴리뉴클레오티드이다. 원래의 코딩 서열로부터 제거되고 천연에서는 연결된 것으로 발견되지 않는 코딩 서열에 작동가능하게 연결된 프로모터는 이종성 프로모터이다. 바이러스 또는 바이러스 벡터의 게놈으로 클로닝된 자리-특이적 재조합 자리(바이러스의 게놈은 천연에서는 그것을 함유하지 않는다)는 이종성 재조합 자리이다. 재조합 효소에 대한 서열을 암호화하는 폴리뉴클레오티드가 재조합효소를 정상적으로 발현하지 않는 세포를 유전적으로 변경하기 위해 사용될 때, 폴리뉴클레오티드와 재조합 효소는 둘 다 세포에 이종성이다.
본 명세서 및 청구항을 통해 사용되는, 용어 "포함하다" 및 그것의 변형인 "포함하는"은 다른 성분, 요소, 완전체, 단계 등에 포괄적이다. 용어 "구성된다" 또는 "구성되는"은 다른 성분, 구성요소, 정수, 단계 등에 배타적이다.
I. 유인원
아데노바이러스
서열
본 발명은 각각이 천연에서 연관된 다른 물질로부터 분리된 유인원 아데노바이러스 40 (SAdV-40), SAdV-31 또는 SAdV-34의 핵산 서열 및 아미노산 서열을 제공한다.
A. 핵산 서열
본원에서 제공되는 SAdV-40 핵산 서열은 SEQ 1D NO: 1의 뉴클레오티드 1 내지 37718을 포함한다. 본원에서 제공되는 SAdV-31핵산 서열은 SEQ ID NO: 32의 뉴클레오티드 1 내지 37828를 포함한다. 본원에 제공되는 SAdV-34 핵산 서열은 SEQ ID NO: 63의 뉴클레오티드 1 내지 37799을 포함한다. 본원에 참고로써 포함되는 서열목록을 참조.
한 구체예에서, 본 발명의 핵산 서열은 각각 SEQ ID NO: 1, 32, 또는 63의 서열에 상보적인 가닥뿐만 아니라 하기 서열의 서열의 대응하는 RNA 및 cDNA 서열 및 그것의 상보적 가닥을 더 포함한다. 다른 구체예에서, 핵산 서열은 서열목록과 98.5% 이상 동일한, 바람직하게는 약 99% 동일한 서열을 더 포함한다. 또한 한 구체예에서, SEQ ID NO: 1, 32, 또는 63 및 그것의 상보적 가닥에서 제공된 서열의 천연 변이체 및 공학적 변형이 포함된다. 이러한 변형은, 예를 들어, 당업계에 알려진 표지, 메틸화, 및 하나 이상의 자연적으로 발생하는 뉴클레오티드의 축퇴 뉴클레오티드로의 치환을 포함한다.
한 구체예에서, SAdV-40, SAdV-31 또는 SAdV-34의 서열의 단편, 및 그것의 상보적 가닥, 그것에 상보적인 cDNA 및 RNA가 제공된다. 적당한 단편은 길이에 있어 적어도 15개의 뉴클레오티드이며, 기능적 단편, 즉, 생물학적 관심이 있는 단편을 포함한다. 예를 들어, 기능적 단편은 요망되는 아데노바이러스 생성물을 발현시킬 수 있고 또는 재조합 바이러스 벡터의 생성에 유용할 수 있다. 이러한 단편은 유전자 서열 및 본원의 표에 열거되는 단편을 포함한다. 표는 SAdV-40, SAdV-31 또는 SAdV-34 서열의 전사체 영역 및 오픈리딩 프레임을 제공한다. 특정 유전자에 대해, 전사체 및 오픈리딩프레임(ORF)은 SEQ ID NO: 1, 32, 또는 63에서 존재하는 상보적인 가닥에 위치된다. 예를 들어, E2b, E4 및 E2a 참조. 암호화된 단백질의 계산된 분자량이 또한 나타난다. SAdV-40, SAdV-31 또는 SAdV-34의 E1a 오픈리딩프레임 및 E2b 오픈리딩프레임은 내부 스플라이스 자리를 함유한다는 것에 주의한다. 이들 스플라이스 자리는 상기 표에서 기록된다.
SAdV-40, SAdV-31 또는 SAdV-34 아데노바이러스 핵산 서열은 치료제로서 및 다양한 벡터 시스템 및 숙주 세포의 구성에서 유용하다. 본원에서 사용되는, 벡터는 네이키드 DNA, 플라스미드, 바이러스, 코스미드 또는 에피솜을 포함하는 어떤 적당한 핵산 분자를 포함한다. 이들 서열 및 생성물은 단독으로 또는 다른 아데노바이러스 서열 또는 분획과 조합하여, 또는 다른 아데노바이러스 또는 비-아데노바이러스 서열로부터의 요소와 조합하여 사용될 수 있다. SAdV-40, SAdV-31 또는 SAdV-34 서열은 안티센스 전달 벡터, 유전자 치료 벡터, 또는 백신 벡터로서 또한 유용하다. 따라서, 추가로 SAdV-40, SAdV-31 또는 SAdV-34 서열을 함유하는 핵산 분자, 유전자 전달 벡터, 및 숙주 세포가 제공된다.
예를 들어, 본 발명은 본 발명의 유인원 Ad ITR 서열을 함유하는 핵산 분자를 포함한다. 다른 예에서, 본 발명은 원하는 Ad 유전자 생성물을 암호화하는 본 발명의 유인원 Ad 서열을 함유하는 핵산 분자를 제공한다. 본 발명의 서열을 사용하여 구성되는 또 다른 핵산 분자는 본원에 제공되는 정보의 관점에서 당업자에게 용이하게 명백할 것이다.
한 구체예에서, 본원에서 확인되는 유인원 Ad 유전자 영역은 세포에 이종성 분자의 전달을 위한 다양한 벡터에서 사용될 수 있다. 예를 들어, 벡터는 패키징 숙주 세포에서 바이러스 벡터를 발생시키는 목적을 위해 아데노바이러스 캡시드 단백질(또는 그것의 단편)의 발현에 대해 발생된다. 이러한 벡터는 트랜스 발현을 위해 설계될 수 있다. 또 다르게는, 이러한 벡터는 원하는 아데노바이러스 기능을 발현시키는 서열, 예를 들어, 하나 이상의 E1a, E1b, 말단 반복 서열, E2a, E2b, E4, E4ORF6 영역을 안정하게 함유하는 세포를 제공하기 위해 설계된다.
게다가, 아데노바이러스 유전자 서열 및 그것의 단편은 헬퍼-의존 바이러스(예를 들어, 필수 기능이 결핍된 아데노바이러스 벡터, 또는 아데노-관련 바이러스(AAV))의 생성에 필요한 헬퍼 기능을 제공하는데 유용하다. 이러한 생성 방법에 대해,SAdV-40, SAdV-31 또는 SAdV-34서열은 인간 Ad에 기술된 것과 유사한 방법인 그러한 방법으로 이용될 수 있다. 그러나, SAdV-40, SAdV-31 또는 SAdV-34 사이의 서열, 서열과 인간 Ad의 그것들의 차이점 때문에, SAdV-40, SAdV-31 또는 SAdV-34 서열의 사용은 rAAV 생성 동안 감염성 아데노바이러스 오염물질을 생성할 수 있는 인간 Ad E1 기능을 전달하는 숙주 세포, 예를 들어, 293 세포에서 헬퍼 기능을 가지는 상동 재조합의 가능성을 크게 최소화하거나 제거한다.
아데노바이러스 헬퍼 기능을 사용하는 rAAV를 생성하는 방법은 인간 아데노바이러스 항원형과 함께 문헌에서 길이로 기술되었다. 예를 들어, 미국 특허 6,258,595 및 그것에 인용된 참고문헌을 참조. 또한, 미국 특허 5,871,982; WO 99/14354; WO 99/15685; WO 99/47691 참조. 이들 방법은 또한 비-인간 영장류 AAV 항원형을 포함하는 비-인간 항원형 AAV의 생성에 사용될 수 있다. 필요한 헬퍼 기능(예를 들어, E1a, E1b, E2a 및/또는 E4ORF6)을 제공하는 SAdV-40, SAdV-31 또는 SAdV-34 서열은 필요한 아데노바이러스 기능을 제공하는데 특히 유용할 수 있는 한편, 어떤 다른 아데노바이러스와 재조합의 가능성을 최소화 또는 제거하는 것은 전형적으로 인간 기원의 rAAV-패키징 세포에서 존재한다. 따라서, SAdV-40, SAdV-31 또는 SAdV-34의 선택된 유전자 또는 오픈리딩프레임은 이들 rAAV 생성 방법에 사용될 수 있다.
또 다르게는, SAdV-40, SAdV-31 또는 SAdV-34의 서열을 기초로 한 재조합 벡터는 이들 방법에 사용될 수 있다. 이러한 재조합 아데노바이러스 유인원 벡터는, 그것의 발현을 제어하는 조절 서열의 제어하에서 예를 들어, 침팬지 Ad 서열이 예를 들어, AAV 3' 및/또는 5' ITRs 및 이식 유전자로 구성되는 rAAV 발현 카세트 옆에 배치되는 하이브리드 침팬지 Ad/AAV를 포함할 수 있다. 당업자는 또 다른 유인원 아데노바이러스 벡터 및/또는 SAdV-40, SAdV-31 또는 SAdV-34 유전자 서열이 아데노바이러스 헬퍼에 의존하여 rAAV 및 다른 바이러스의 생성에 유용할 것임을 인식할 것이다.
또 다른 구체예에서, 핵산 분자는 숙주 세포에서 선택된 아데노바이러스 유전자 생성물의 전달 및 발현을 위해 설계되어 원하는 생리적 효과를 이룬다. 예를 들어, SAdV-40, SAdV-31 또는 SAdV-34 E1a 단백질을 암호화하는 서열을 함유하는 핵산 분자는 암 치료제로서 사용을 위해 피험자에게 전달될 수 있다. 선택적으로, 이러한 분자는 지질-계 담체에서 제형화되고, 바람직하게는 암세포를 표적화한다. 이러한 제형은 다른 암 치료제(예를 들어, 시스플라틴, 탁솔 등)와 조합될 수 있다. 본원에 제공되는 아데노바이러스 서열에 대한 또 다른 사용은 당업자에게 용이하게 명백할 것이다.
게다가, 당업자는 SAdV-40, SAdV-31 또는 SAdV-34 서열이 치료 및 면역 분자의 시험관 내, 생체 밖 또는 생체 내 전달을 위해 다양한 바이러스 및 비-바이러스 벡터 시스템에 대한 사용에 용이하게 적용될 수 있다는 것을 용이하게 이해할 것이다. 예를 들어, SAdV-40, SAdV-31 또는 SAdV-34 유인원 Ad 서열은 다양한 rAd 및 비-rAd 벡터 시스템에 이용될 수 있다. 이러한 벡터 시스템은, 예를 들어, 플라스미드, 렌티바이러스, 레트로바이러스, 수두바이러스, 우두 바이러스, 및 특히 아데노-연관 바이러스 시스템을 포함할 수 있다. 이러한 벡터 시스템의 선택은 본 발명의 제한이 아니다.
본 발명은 추가로 본 발명의 유인원 및 유인원-유래 단백질의 생성에 유용한 분자를 제공한다. 본 발명의 유인원 Ad DNA 서열을 포함하는 폴리뉴클레오티드를 전달하는 이러한 분자는 네이키드 DNA, 플라스미드, 바이러스 또는 다른 유전적 구성요소의 형태일 수 있다.
B.
SAdV
-40,
SAdV
-31 또는
SAdV
-34
아데노바이러스
단백질
본원에 설명되는 아데노바이러스 핵산에 의해 암호화되는 SAdV-40, SAdV-31 또는 SAdV-34 아데노바이러스의 유전자 생성물, 예컨대, 단백질, 효소 및 그것의 단편이 제공된다. 더 나아가, 다른 방법에 의해 발생되는 이들 핵산 서열에 의해 암호화된 아미노산 서열을 가지는 SAdV-40, SAdV-31 또는 SAdV-34 단백질, 효소, 및 그것의 단편이 포함된다. 이러한 단백질은 상기 표에서 확인되는 오픈리딩프레임에 의해 암호화되는 것, 하기 표의 단백질(또한 서열목록에서 나타냄), 및 단백질 및 폴리펩티드의 단편을 포함한다.
따라서, 한 양태에서, 실질적으로 순수한, 즉, 다른 바이러스 및 단백질성 단백질이 없는 독특한 유인원 아데노바이러스 단백질이 제공된다. 바람직하게는, 이들 단백질은 적어도 10% 상동성, 더 바람직하게는 60% 상동성, 및 가장 바람직하게는 95% 상동성이다.
한 구체예에서, 독특한 유인원-유래 캡시드 단백질이 제공된다. 본원에서 사용된 바와 같은, 유인원-유래 캡시드 단백질은, 제한 없이, 키메라 캡시드 단백질, 융합 단백질, 인공 캡시드 단백질, 합성 캡시드 단백질, 및 재조합 캡시드 단백질을 포함하여, 이들 단백질의 의미에 대한 제한 없이, 상기 정의한 바와 같은 SAdV-40, SAdV-31 또는 SAdV-34 캡시드 단백질 또는 그것의 단편을 함유하는 어떤 아데노바이러스 캡시드 단백질을 포함한다.
적당하게, 이들 유인원-유래 캡시드 단백질은 다른 아데노바이러스 항원형의 캡시드 영역 또는 그것의 단편, 또는 본원에서 설명되는 바와 같은 변형된 유인원 캡시드 단백질 또는 단편과 조합하여 하나 이상의 SAdV-40, SAdV-31 또는 SAdV-34 영역 또는 그것의 단편(예를 들어, 헥손, 펜톤, 섬유 또는 그것의 단편)을 함유한다. 본원에서 사용되는 바와 같은 "변형된 굴성과 연관된 캡시드 단백질의 변형"은 변경된 캡시드 단백질, 즉, 펜톤, 헥손 또는 섬유 단백질 영역, 또는 그것의 단편, 예로써, 섬유 영역의 혹(knob) 도메인, 또는 이를 암호화하는 폴리뉴클레오티드를 포함하는데, 특이성은 변경된다. 유인원-유래 캡시드는 인간 또는 비-인간 기원일 수 있는 하나 이상의 본 발명 또는 다른 Ad 항원형과 함께 구성될 수 있다. 이러한 Ad는 ATCC, 상업적 및 학업적 공급원을 포함하는 다양한 공급원으로부터 획득될 수 있고, 또는 Ad의 서열은 GenBank 또는 다른 적당한 공급원으로부터 획득될 수 있다.
SAdV-40 [SEQ ID NO:6], SAdV-31 [SEQ ID NO: 37], 또는 SAdV-34 [SEQ ID NO: 68]의 펜톤 단백질의 아미노산 서열이 제공된다. 적절하게는, 이들 펜톤 단백질, 또는 그것의 독특한 단편은 다양한 목적을 위해 이용될 수 있다. 적절한 단편의 예는 각각 상기 제공된 아미노산 넘버링 및 각각 SEQ ID NO:6, 37 또는 68에 기초한 약 50, 100, 150, 또는 200개의 아미노산의 N-말단 및/또는 C-말단의 절단(truncation)을 가지는 펜톤을 포함한다. 다른 적당한 단편은 더 짧은 내부의, C-말단의 또는 N-말단의 단편을 포함한다. 추가로, 펜톤 단백질은 당업자에게 공지된 다양한 목적을 위해 변형될 수 있다.
또한 SAdV-40 [SEQ ID NO: 11], SAdV-31 [SEQ ID NO: 42], 또는 SAdV-34 [SEQ ID NO: 73]의 헥손 단백질의 아미노산 서열이 제공된다. 적절하게는, 이들 헥손 단백질, 또는 그것의 독특한 단편은 다양한 목적을 위해 이용될 수 있다. 적절한 단편의 예는 상기 제공된 아미노산 넘버링 및 각각 SEQ ID NO: 11, 42 또는 73에 기초한 약 50, 100, 150, 200, 300, 400, 또는 500개의 아미노산의 N-말단 및/또는 C-말단의 절단을 가지는 헥손을 포함한다. 다른 적당한 단편은 더 짧은 내부의, C-말단, 또는 N-말단의 단편을 포함한다. 예를 들어, 한 적당한 단편은 헥손 단백질, 지정된 DE1 및 FG1, 또는 그것의 고도가변 영역의 루프 영역(도메인)이다. 이러한 단편은 각각 SEQ ID NO: 11, 42 또는 73에 대하여 유인원 헥손 단백질의 아미노산 잔기 약 125 내지 443; 약 138 내지 441, 또는 더 적은 단편을 걸치는 영역, 예로써, 약 잔기 138 내지 잔기 163; 약 170 내지 약 176; 약 195 내지 약 203; 약 233 내지 약 246; 약 253 내지 약 374; 약 287 내지 약 297; 및 약 404 내지 약 430을 걸치는 것을 포함한다. 다른 적당한 단편은 당업자에 의해 용이하게 확인될 수 있다. 추가로, 헥손 단백질은 당업계에 공지된 다양한 목적을 위해 변형될 수 있다. 헥손 단백질이 아데노바이러스의 항원형에 대한 결정요인이기 때문에, 이러한 인공 헥손 단백질은 인공 항원형을 가지는 아데노바이러스를 초래할 수 있다. 다른 인공 캡시드 단백질은 또한 침팬지 Ad 펜톤 서열 및/또는 본 발명의 섬유 서열 및/또는 그것의 단편을 사용하여 구성될 수 있다.
한 구체예에서, SAdV-40, SAdV-31 또는 SAdV-34 헥손 단백질의 서열을 이용하는 변경된 헥손 단백질을 가지는 아데노바이러스가 발생될 수 있다. 헥손 단백질을 변경하는 한 적절한 방법은 참고로써 포함되는 미국 특허 5,922,315호에서 기술된다. 이 방법에서, 아데노바이러스 헥손의 적어도 하나의 루프 영역은 다른 아데노바이러스 항원형의 적어도 하나의 루프 영역으로 변경된다. 따라서, 이러한 변경된 아데노바이러스 헥손 단백질의 적어도 하나의 루프 영역은 SAdV-39의 유인원 Ad 헥손 루프 영역이다. 한 구체예에서, SAdV-40, SAdV-31 또는 SAdV-34 헥손 단백질의 루프 영역은 다른 아데노바이러스 항원형으로부터 루프 영역으로써 대체된다. 다른 구체예에서, SAdV-40, SAdV-31 또는 SAdV-34 헥손의 루프 영역은 다른 아데노바이러스 항원형의 루프 영역을 대체하기 위해 사용된다. 적절한 아데노바이러스 항원형은 본원에서 설명되는 바와 같은 인간과 비-인간 항원형 중으로부터 용이하게 선택될 수 있다. 적당한 항원형의 선택은 본 발명에서 제한되지 않는다. SAdV-40, SAdV-31 또는 SAdV-34 헥손 단백질 서열에 대한 또 다른 사용은 당업자에게 용이하게 명백할 것이다.
SAdV-40 [SEQ ID NO:20], SAdV-31 [SEQ ID NO: 51], 또는 SAdV-34 [SEQ ID NO: 82]의 섬유 단백질의 아미노산 서열이 제공된다. 적절하게는, 이 섬유 단백질, 또는 그것의 독특한 단편은 다양한 목적을 위해 이용될 수 있다. 한 적절한 단편은 SEQ ID NO: 20, 51, 또는 82 내에 위치되는 섬유 혹이다. 다른 적절한 단편의 예는 SEQ ID NO: 20, 51, 또는 82에서 제공되는 아미노산 넘버링에 기초하여 약 50, 100, 150, 또는 200 아미노산의 N-말단의 및/또는 C-말단의 절단을 가지는 섬유를 포함한다. 또 다른 적절한 단편은 내부 단편을 포함한다. 추가로, 섬유 단백질은 당업자에게 공지된 다양한 기술을 사용하여 변형될 수 있다.
SAdV-40, SAdV-31 또는 SAdV-34의 단백질의 독특한 단편은 길이에 있어서 적어도 8개의 아미노산이다. 그러나, 다른 원하는 길이의 단편이 용이하게 이용될 수 있다. 게다가, 변형은 SAdV-40, SAdV-31 또는 SAdV-34 유전자 생성물의 수율 및/또는 발현을 향상시키기 위해 도입될 수 있고, 예를 들어, SAdV-40, SAdV-31 또는 SAdV-34 유전자 생성물의 모두 또는 단편이 향상을 위해 융합 파트너와 융합되는(직접 또는 링커를 통해) 융합 분자의 구성이 본원에서 제공된다. 다른 적절한 변형은, 제한 없이, 보통 절단되는 전- 또는 후-단백질을 제거하기 위해 및 성숙 단백질 또는 효소 및/또는 비밀 유전자 생성물을 제공하기 위한 코딩 영역의 돌연변이를 제공하기 위해 코딩 영역(예를 들어, 단백질 또는 효소)의 절단을 포함한다. 또 다른 변형은 당업자에게 용이하게 명백할 것이다. 더 나아가 본원에 제공된 SAdV-40, SAdV-31 또는 SAdV-34 단백질과 적어도 약 99% 동일성을 가지는 단백질이 포함된다.
본원에서 설명되는 바와 같은, SAdV-40, SAdV-31 또는 SAdV-34의 아데노바이러스 캡시드 단백질을 함유하는 본 발명의 벡터는 중화벡터가 다른 Ad 항원형계 벡터 뿐만 아니라 다른 바이러스 벡터의 유효성을 감소시키는 용도에서의 사용에 특히 적합하다. rAd 벡터는 반복 유전자 치료 또는 부스팅 면역 반응(백신 타이터)을 위한 재투여에서 특히 유리하다.
특정 환경 하에서, 항체를 발생시키기 위한 하나 이상의 SAdV-40, SAdV-31 또는 SAdV-34 유전자 생성물(예를 들어, 캡시드 단백질 또는 그것의 단편)을 사용하는 것이 바람직할 수 있다. 본원에서 사용되는 용어 "항체"는 에피토프에 특이적으로 결합할 수 있는 면역글로불린 분자를 말한다. 항체는, 예를 들어, 고친화도 폴리클로날 항체, 모노클로날 항체, 합성 항체, 키메라 항체, 재조합 항체 및 인간화된 항체를 포함하는 다양한 형태로 존재할 수 있다. 이러한 항체는 면역글로불린 분류 IgG, IgM, IgA, IgD 및 IgE로부터 기원한다.
이러한 항체는 당업계에 알려진 어떤 다수의 방법을 사용하여 발생될 수 있다. 적절한 항체는 잘-알려진 전통적인 기술, 예를 들어, Kohler 및 Milstein, 및 그것의 많은 공지된 변형에 의해 발생될 수 있다. 유사하게, 바람직한 고역가 항체는 이들 항원에서 개발된 모노클로날 또는 폴리클로날 항체에 대한 공지된 재조합 기술을 적용함으로써 발생될 수 있다[예를 들어, PCT 특허 출원 No. PCT/GB85/00392; 영국 특허 출원 공개 번호 GB2188638A; Amit et al ., 1986 Science, 233:747-753; Queen et al ., 1989 Proc . Nat'l . Acad . Sci . USA, 86: 10029-10033; PCT 특허 출원 번호 PCT/WO9007861; 및 Riechmann et al., Nature, 332:323-327 (1988); Huse et al, 1988a Science, 246: 1275-1281 참조]. 또 다르게는, 항체는 본 발명의 항원에 동물 또는 인간 항체의 상보성 결정 영역을 조작함으로써 생성될 수 있다. 예를 들어, E. Mark and Padlin, "Humanization of Monoclonal Antibodies", Chapter 4, The Handbook of Experimental Pharmacology, Vol. 113, The Pharmacology of Monoclonal Antibodies, Springer-Verlag (June, 1994); Harlow et al ., 1999, Using Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory Press, NY; Harlow et al ., 1989, Antibodies: A Laboratory Manual, Cold Spring Harbor, New York; Houston et al ., 1988, Proc . Natl. Acad . Sci USA 85:5879-5883; 및 Bird et al ., 1988, Science 242:423-426 참조. 추가로 본 발명에 의해 항-유전자형 항체(Ab2) 및 항-항-유전자형 항체(Ab3)가 제공된다. 예를 들어, M. Wettendorff et al ., "Modulation of anti-tumor immunity by anti-idiotypic antibodies." In Idiotypic Network and Diseases, ed. by J. Cerny and J. Hiernaux, 1990 J. Am . Soc . Microbiol ., Washington DC: pp. 203-229]. 이들 항-유전자형 및 항-항-유전자형 항체는 당업계에 공지된 기술을 사용하여 생성된다. 이들 항체는 진단적 및 임상적 방법 및 키트를 포함하는 다양한 목적을 위해 사용될 수 있다.
특정 환경 하에서, SAdV-40, SAdV-31 또는 SAdV-34 유전자 생성물, 항체 또는 본 발명의 다른 구조체에 검출가능한 표지 또는 태그를 도입하는 것이 바람직할 수 있다. 본원에서 사용되는 바와 같은, 검출가능한 표지는 단독으로 또는 다른 분자와 상호작용하여, 검출가능한 신호를 제공할 수 있는 분자이다. 가장 바람직하게는, 표지는, 예를 들어, 면역 조직 화학 분석 또는 면역 형광 현미경검사에 의해 시각적으로 검출가능하다. 예를 들어, 적당한 표지는 플루오르세인 이소티오시아네이트 (FITC), 피코에리트린 (PE), 알로피코시아닌(APC), 코리포스핀-O (CPO) 또는 탠덤 염료, PE-시아닌-5 (PC5), 및 PE-텍사스 레드(ECD)를 포함한다. 모든 이들 형광 염료는 상업적으로 이용가능하고, 그것들의 사용은 당업계에 공지되어 있다. 다른 유용한 표지는 콜로이드 골드 표지를 포함한다. 또 다른 유용한 표지는 방사성 화합물 또는 원소를 포함한다. 추가적으로, 표지는 분석에서 측색 신호를 나타내기 위해 작동하는 다양한 효소 시스템을 포함하며, 예를 들어, 글루코오스 옥시다아제(기질로서 글루코오스를 사용)는 페록시다아제 및 테트라메틸 벤지딘(TMB)과 같은 수소 도너의 존재하에서 푸른색으로서 보이는 산화된 TMB를 생성하는 생성물로서 과산화물을 방출한다. 다른 예는 ATP, 글루코오스, 및 NAD+와 반응하는 글루코오스-6-포스페이트 탈수소효소와 함께 양고추냉이과산화효소 (HRP), 알칼리 포스파타아제 (AP), 및 헥소키나아제를 포함하여, 특히 340 nm 파장에서 증가된 흡광도로서 검출되는 NADH를 얻는다.
본원에서 기술되는 방법에서 이용되는 다른 표지 시스템은 다른 수단, 예를 들어, 주입된 염료가 적용가능한 분석에서 결과 복합체의 존재하에서 시각적 신호 표시를 제공하기 위한 표적 서열과 콘쥬게이트를 형성하는 효소 대신에 사용되는 착색 라텍스 마이크로입자[Bangs Laboratories, Indiana]에 의해 검출가능하다.
원하는 분자와 표지를 커플링 또는 결합하는 방법은 마찬가지로 통상적이며 당업자에게 공지되어 있다. 표지 부착의 공지된 방법이 기술된다[예를 들어, Handbook of Fluorescent probes and Research Chemicals, 6th Ed., R.P.M. Haugland, Molecular Probes, Inc., Eugene, OR, 1996; Pierce Catalog and Handbook, Life Science and Analytical Research Products, Pierce Chemical Company, Rockford, IL, 1994/1995 참조]. 따라서, 표지 및 커플링 방법의 선택은 본 발명을 제한하지 않는다.
SAdV-40, SAdV-31 또는 SAdV-34의 서열, 단백질, 및 단편은 재조합 생성물, 화학적 합성, 또는 다른 합성 수단을 포함하는 임의의 적절한 수단에 의해 생성될 수 있다. 적절한 생성 기술은 당업자에게 잘 공지되어 있다. 예를 들어, Sambrook et al, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Press (Cold Spring Harbor, NY) 참조. 또 다르게는, 펩티드는 또한 잘 공지된 고체 상 펩티드 합성 방법(Merrifield, J. Am . Chem . Soc, 85:2149 (1962); Stewart and Young, Solid Phase Peptide Synthesis (Freeman, San Francisco, 1969) pp. 27-62)에 의해 합성될 수 있다. 이들 및 다른 적절한 생성 방법은 당업자의 지식 내이며, 본 발명의 범위를 제한하지 않는다.
게다가, 당업자는 SAdV-40, SAdV-31 또는 SAdV-34 서열이 치료 및 면역 분자의 시험관 내, 생체 밖 또는 생체 내 전달을 위한 다양한 바이러스 및 비-바이러스 벡터 시스템을 위한 사용에 용이하게 적용될 수 있다는 것을 용이하게 이해할 것이다. 예를 들어, 한 구체예에서, 유인원 Ad 캡시드 단백질 및 본원에서 기술되는 다른 유인원 아데노바이러스 단백질은 비-바이러스, 유전자의 단백질계 전달, 단백질 및 기타 바람직한 진단적, 치료적 및 면역적 분자에 대해 사용된다. 한 이러한 구체예에서, 본 발명의 단백질은 아데노바이러스에 대한 수용체와 함께 세포를 표적화하기 위한 분자에 직접 또는 간접적으로 연결된다. 바람직하게는, 헥손, 펜톤, 섬유 또는 세포 표면 수용체를 위한 리간드를 가지는 그것의 단편과 같은 캡시드 단백질이 이러한 표적을 위해 선택된다. 전달에 적당한 분자는 본원에서 기술되는 치료적 분자와 그것의 유전자 생성물 중에서 선택된다. 지질, 폴리Lys 등을 포함하는 다양한 링커가 링커로서 이용될 수 있다. 예를 들어, 유인원 펜톤 단백질은 Medina-Kauwe LK, et al, Gene Ther . 2001년 5월; 8(10):795-803 및 Medina-Kauwe LK, et al, Gene Ther . 2001년 12월; 8(23): 1753-1761에서 기술되는 것과 유사한 방법으로 유인원 펜톤 서열을 사용하여 융합 단백질의 생성에 의한 목적을 위해 용이하게 이용될 수 있다. 또 다르게는, 유인원 Ad 단백질 IX의 아미노산 서열은 미국 특허 출원 20010047081에 기술되는 바와 같은 세포 표면 수용체에 벡터를 표적화하기 위해 이용될 수 있다. 적당한 리간드는 CD40 항원, RGD-함유 또는 폴리리신-함유 서열 등을 포함한다. 예를 들어, 헥손 단백질 및/또는 섬유 단백질을 포함하는 또 다른 유인원 Ad 단백질은 이들 및 유사한 목적을 위해 사용될 수 있다.
또 다른 SAdV-40, SAdV-31 또는 SAdV-34 아데노바이러스 단백질은 당업자에게 용이하게 명백할 다양한 목적을 위하여 단독으로, 또는 다른 아데노바이러스 단백질과 조합하여 사용될 수 있다. 게다가, SAdV 아데노바이러스 단백질의 또 다른 사용은 당업자에게 용이하게 명백할 것이다.
II
. 재조합
아데노바이러스
벡터
본원에 설명되는 조성물은 치료 또는 백신 목적을 위해 세포에 이종성 분자를 전달하는 벡터를 포함한다. 본원에서 사용되는, 벡터는 제한 없이, 네이키드 DNA, 파지, 트랜스포존, 코스미드, 에피솜, 플라스미드, 또는 바이러스를 포함하는 어떤 유전적 요소를 포함할 수 있다. 이러한 벡터는 SAdV-40, SAdV-31 또는 SAdV-34 및 미니유전자의 유인원 아데노바이러스를 함유한다. "미니유전자" 또는 "발현 카세트"는 숙주 세포에서 유전자 생성물의 번역, 전사 및/또는 발현을 작동하는데 필요한 선택된 이종성 유전자 및 다른 조절 요소의 조합을 의미한다.
전형적으로, SAdV-40, SAdV-31 또는 SAdV-34 -유래된 아데노바이러스 벡터는 설계되어 선택된 아데노바이러스 유전자에 고유한 영역에서 미니유전자는 다른 아데노바이러스 서열을 함유하는 핵산 분자에 위치된다. 미니유전자는 원한다면, 영역의 기능을 방해하기 위해 존재하는 유전자 영역에 도입될 수 있다. 또 다르게는, 미니유전자는 부분적으로 또는 완전히 결실된 아데노바이러스 유전자의 자리에 삽입될 수 있다. 예를 들어, 미니유전자는 특히 선택될 수 있는 기능적 E1 결실 또는 기능적 E3 결실의 자리와 같은 자리에서 위치될 수 있다. 용어 "기능적으로 결실된" 또는 "기능적 결실"은 유전자 영역의 충분한 양이 예를 들어, 돌연변이 또는 변형에 의해 제거 또는 다르게는 손상되어, 유전자 영역은 유전자 발현의 기능적 생성물을 더 이상 생성할 수 없음을 의미한다. 원한다면, 전체 유전자 영역이 제거될 수도 있다. 유전자 파괴 또는 결실을 위한 다른 적절한 자리는 본 출원의 어디에서나 논의된다.
예를 들어, 재조합 바이러스의 발생에 유용한 생성 벡터에 대해, 벡터는 미니유전자 및 아데노바이러스 게놈의 5' 말단 또는 아데노바이러스 게놈의 3' 말단 중 하나, 또는 아데노바이러스 게놈의 5'과 3' 둘 다를 함유할 수 있다. 아데노바이러스 게놈의 5' 말단은 패키징 및 복제에 필요한 5' 시스-구성요소; 즉, 5' 역위 말단 반복 (ITR) 서열(복제의 기원으로서 작용) 및 본래의 5' 패키징 인핸서 도메인(E1 프로모터를 위한 패키징 선형 Ad 게놈 및 인핸서 요소에 필요한 서열을 함유)을 함유한다. 아데노바이러스 게놈의 3' 말단은 패키징 및 단백질 막화(encapsidation)에 필요한 3' 시스-구성요소(ITR을 포함)를 포함한다. 적절하게는, 재조합 아데노바이러스는 5' 및 3' 아데노바이러스 시스-구성요소를 함유하며, 미니유전자는 5' 및 3' 아데노바이러스 서열 사이에 위치된다. SAdV-40, SAdV-31 또는 SAdV-34 기초 아데노바이러스 벡터는 또한 추가 아데노바이러스 서열을 함유할 수 있다.
적절하게는, 이들 SAdV-40, SAdV-31 또는 SAdV-34 기초 아데노바이러스 벡터는 본 발명의 아데노바이러스 게놈으로부터 유래된 하나 이상의 아데노바이러스 구성요소를 함유할 수 있다. 한 구체예에서, 벡터는 SAdV-40, SAdV-31 또는 SAdV-34로부터의 아데노바이러스 ITR 및 동일한 아데노바이러스 항원형으로부터의 추가 아데노바이러스 서열을 함유한다. 다른 구체예에서, 벡터는 ITR을 제공하는 것보다 다른 아데노바이러스 항원형으로부터 유래되는 아데노바이러스 서열을 함유한다.
본원에서 정의되는 바와 같이, 슈도타입화된(pseudotyped) 아데노바이러스는 아데노바이러스의 캡시드 단백질이 ITR을 제공하는 아데노바이러스 보다 다른 아데노바이러스로부터 오는 아데노바이러스를 말한다.
추가로, 키메라 또는 하이브리드 아데노바이러스는 당업자에게 공지된 기술을 사용하여 본원에 기술된 아데노바이러스를 사용하여 구성될 수 있다. 예를 들어, 미국 특허 US 7,291,498호 참조.
ITR의 아데노바이러스 공급원 및 벡터에 존재하는 어떤 다른 아데노바이러스 서열의 공급원은 본 발명을 제한하지 않는다. 다양한 아데노바이러스 균주가 American Type Culture Collection, Manassas, Virginia로부터 이용가능하고, 또는 다양한 상업적 및 기관의 공급원으로부터 이용가능하다. 추가로, 많은 이러한 균주의 서열은 예를 들어, PubMed 및 GenBank를 포함하는 다양한 데이터베이스로부터 이용가능하다. 다른 유인원 또는 인간 아데노바이러스로부터 제조된 상동 아데노바이러스 벡터는 공개된 문헌에서 기술된다[예를 들어, 미국 특허 5,240,846호 참조]. 다수의 아데노바이러스 종류의 DNA 서열은 타입 Ad5[GenBank 등록 번호 M73260]를 포함하여, GenBank로부터 이용가능하다. 아데노바이러스 서열은 항원형 2, 3, 4, 7, 12 및 40과 같은 어떤 공지된 아데노바이러스 항원형으로부터 얻을 수 있고, 또한 어떤 본원에서 확인되는 인간형을 포함한다. 유사하게 비-인간 동물(예를 들어, 유인원)을 감염시키는 것으로 알려진 아데노바이러스는 또한 본 발명의 벡터 구조체에서 사용될 수 있다. 예를 들어, 미국 특허 6,083,716호 참조.
바이러스 서열, 헬퍼 바이러스(필요하다면), 및 재조합 바이러스 입자, 및 다른 벡터 성분 및 본원에 설명되는 벡터의 구조체에서 사용되는 서열은 상기 기술된 바와 같이 획득된다. 본 발명의 SAdV-40, SAdV-31 또는 SAdV-34 유인원 아데노바이러스 서열의 DNA 서열은 벡터 및 이러한 벡터의 제조에 유용한 셀 라인을 구성하기 위해 사용된다.
서열 결실, 삽입, 및 다른 돌연변이를 포함하는 본 발명의 벡터를 형성하는 핵산 서열의 변형은 표준 분자 생물학적 기술을 사용하여 발생될 수 있고, 본 구체예의 범주 내이다.
A. "미니유전자"
이식 유전자의 선택, "미니유전자"의 클로닝 및 구성 및 바이러스 벡터에 그것의 삽입을 위해 사용되는 방법은 본원에서 제공되는 교시가 주어지는 당업계의 기술 내이다.
1. 이식 유전자
이식 유전자는 관심의 폴리펩티드, 단백질, 또는 다른 생성물을 암호화하는 이식 유전자 옆에 위치하는 벡터 서열에 이종성인 핵산 서열이다. 핵산 코딩 서열은 숙주 세포에서 이식 유전자 전사, 번역 및/또는 발현을 허용하는 방식으로 조절 성분에 작동가능하게 연결된다.
이식 유전자 서열의 조성은 결과 벡터가 위치될 곳에서 사용에 의존할 것이다. 예를 들어, 한 종류의 이식 유전자 서열은 발현이 검출가능한 신호를 생성할 때 리포터 서열을 포함한다. 이러한 리포터 서열은, 제한 없이, DNA 서열 암호화 β-락타마아제, β-갈락토시다아제(LacZ), 알칼린 포스파타아제, 티미딘 키나아제, 녹색 형광 단백질(GFP), 클로람페니콜 아세틸트랜스페라아제(CAT), 루시페라아제, 예를들어, CD2, CD4, CD8를 포함하는 막 결합 단백질, 인플루엔자 헤마그글루티닌 단백질, 및 당업계에 잘 공지된 다른 것을 그것과 관련된 고친화도 항체에서 포함하며, 또는 통상적인 수단, 및 특히 헤마그글루티닌 또는 Myc로부터 항원 태그 도메인에 적절하게 융합된 막 결합 단백질을 포함하는 융합 단백질에 의해 생성될 수 있다. 이들 코딩 서열은, 그것의 발현을 작동시키는 조절 요소와 결합될 때, 효소, 방사선 촬영, 측색, 형광 또는 다른 분광기 분석, 형광 활성화 세포 정렬 분석 및 효소면역분석(ELISA), 방사면역측정법(RIA) 및 면역 조직 화학을 포함하는 면역 분석을 포함하는 통상적인 수단에 의해 검출가능한 신호를 제공한다. 예를 들어, 마커 서열은 LacZ 유전자이며, 신호를 전달하는 벡터의 존재는 베타-갈락토시다아제 활성에 대한 분석에 의해 검출된다. 이식 유전자가 GFP 또는 루시페라아제인 경우, 신호를 전달하는 벡터는 광도계에서 색 또는 광 생성에 의해 시각적으로 측정될 수있다.
한 구체예에서, 이식 유전자는 단백질, 펩티드, RNA, 효소, 또는 촉매적 RNA와 같은 생물 및 의학에서 유용한 생성물을 암호화하는 비-마커 서열이다. 바람직한 RNA 분자는 tRNA, dsRNA, 리보솜 RNA, 촉매적 RNA, 및 안티센스 RNA를 포함한다. 유용한 RNA 서열의 한 예는 처치 동물에서 표적 핵산 서열의 발현을 끝내는 서열이다.
이식 유전자는 암 치료제 또는 백신으로서, 면역 반응의 유발, 및/또는 예방 백신 목적을 위한 예를 들어, 유전적 결함의 치료에 사용될 수 있다. 본원에서 사용되는 바와 같은, 면역 반응의 유발은 분자에서 T 세포 및/또는 체액성 면역반응을 유발하는 분자의 능력(예를 들어, 유전자 생성물)을 말한다. 본 발명은 추가로 예를 들어, 멀티-서브유닛 단백질에 의해 야기되는 질환을 고치거나 또는 완화하기 위해 다양한 이식 유전자를 사용하는 것을 포함한다. 특정 상황에서, 다른 이식 유전자는 단백질의 각 서브유닛을 암호화하고, 또는 다른 펩티드 또는 단백질을 코딩하기 위해 사용될 수 있다. 이는 단백질 서브유닛을 암호화하는 DNA의 크기가 클 때, 예를 들어, 면역글로불린, 혈소판-유래 성장인자, 또는 디스트로핀 단백질에 대해 바람직하다. 멀티-서브유닛 단백질을 생성하기 위한 세포를 위해, 세포는 각각의 다른 서브유닛을 함유하는 재조합 바이러스로 감염된다. 또 다르게는, 단백질의 다른 서브유닛은 동일한 이식 유전자에 의해 암호화될 수 있다. 이 경우에, 단일 이식 유전자는 내부 리보자임 유입 자리(IRES)에 의해 분리된 각 서브유닛에 대한 DNA와 함께, 각각의 서브유닛을 암호화하는 DNA를 포함한다. 이는 각각의 서브유닛을 암호화하는 DNA의 자리가 작을 때, 예를 들어, 서브유닛 및 IRES를 암호화하는 DNA의 전체 크기가 5 킬로베이스 미만일 때, 바람직하다. IRES에 대한 대안으로서, DNA는 번역-후 사건에서 자기-절단하는 2A 펩티드를 암호화하는 서열에 의해 분리될 수 있다. 예를 들어, ML. Donnelly, et al ., J. Gen . Virol ., 78(Pt 1): 13-21 (1997년 1월); Furler, S., et al , Gene Ther ., 8(11):864-873 (2001년 6월); Klump H., et al , Gene Ther ., 8(10):811-817(2001년 5월) 참조. 이 2A 펩티드는 IRES보다 상당히 더 작으며, 공간이 제한 인자일 때 사용에 적합하도록 만든다. 그러나, 선택된 이식 유전자가 어떤 생물학적으로 활성인 생성물 또는 다른 생성물, 예를 들어, 연구에 바람직한 생성물을 암호화할 수도 있다.
적당한 이식 유전자는 당업자에 의해 용이하게 선택될 수 있다. 이식 유전자의 선택은 이 구체예를 제한하는 것으로 고려되지 않는다.
2. 조절 요소
미니유전자에 대해 상기 확인된 주요 요소에 더하여, 벡터는 또한 플라스미드 벡터로 트랜스펙팅된 또는 본 발명에 의해 생성되는 바이러스로 감염된 세포에서 그것의 전사, 번역 및/또는 발현을 허용하는 방식으로 이식 유전자에 작동가능하게 연결되는 필요한 통상적인 조절 요소를 포함한다. 본원에 사용되는 바와 같은, "작동가능하게 연결된" 서열은 관심의 유전자와 인접하는 발현 조절 서열 및 트랜스에서 또는 관심의 유전자를 조절하기 위한 거리에서 작용하는 발현 조절 서열을 둘 다 포함한다.
발현 조절 서열은 적절한 전사, 개시, 종결, 프로모터 및 인핸서 서열; 스플라이싱 및 폴리아데닐화(폴리A) 신호와 같은 효율적인 RNA 처리 신호; 세포질 mRNA를 안정화하는 서열; 번역 효율을 향상시키는 서열(즉, Kozak 일치 서열); 단백질 안정성을 향상시키는 서열; 및 필요하다면, 암호화된 생성물의 분비를 향상시키는 서열을 포함한다.
원래의, 구성의, 유도의 및/또는 조직-특이적인 프로모터를 포함하는 매우 다수의 발현 조절 서열은 당업계에 공지되어 있으며 이용될 수 있다. 구성 프로모터의 예는, 제한없이 로우스육종바이러스 (RSV) LTR 프로모터(선택적으로 RSV 인핸서와 함께), 시토메갈로 바이러스(CMV) 프로모터(선택적으로 CMV 인핸서와 함께)[예를 들어, Boshart et al, Cell, 41:521-530 (1985) 참조], SV40 프로모터, 디히드로폴레이트 환원효소 프로모터, β-액틴 프로모터, 포스포글리세롤 키나아제(PGK) 프로모터, 및 EF1α 프로모터[Invitrogen]를 포함한다.
유도성 프로모터는 유전자 발현의 조절을 허용하고 외인성으로 공급된 화합물, 온도와 같은 환경적 인자, 또는 특이적인 생리적 상태의 존재, 예를 들어, 급성 병기, 세포의 특정 분화 상태, 또는 단지 세포를 복제하는 것에 의해 조절될 수 있다. 유도성 프로모터 및 유도성 시스템은, 제한 없이, Invitrogen, Clontech 및 Ariad를 포함하는 다양한 상업적 공급원으로부터 이용가능하다. 많은 다른 시스템이 기술되었고 당업자에 의해 용이하게 선택될 수 있다. 예를 들어, 유도성 프로모터는 아연-유도성 양 메탈로티오닌(MT) 프로모터 및 덱사메타손(Dex)-유도성 마우스 유방 종양 바이러스 (MMTV) 프로모터를 포함한다. 다른 유도성 시스템은 T7 폴리머라아제 프로모터 시스템[WO 98/10088]; 엑디손 곤충 프로모터 [No et al, Proc. Natl . Acad . Sci . USA , 93:3346-3351 (1996)], 테트라사이클린-억제성 시스템[Gossen et al , Proc . Natl . Acad . Sci . USA, 89:5547-5551 (1992)], 테트라사이클린-유도성 시스템[Gossen et al , Science , 268:1766-1769 (1995), 또한 Harvey et al , Curr . Opin . Chem . Biol ., 2:512-518 (1998) 참조]을 포함한다. 다른 시스템은 카스트라디올(castradiol), 디페놀 무리슬레론(diphenol murislerone)을 사용하는 FK506 다이머, VP16 또는 p65, RU486-유도성 시스템[Wang et al, Nat. Biotech., 15:239-243 (1997) 및 Wang et al , Gene Ther ., 4:432-441 (1997)] 및 라파마이신-유도성 시스템[Magari et al , J. Clin . Invest ., 100:2865-2872 (1997)]을 포함한다. 일부 유도성 프로모터의 유효성은 시간에 따라 증가한다. 이러한 경우에, 탠덤에서 다양한 억제물질을 삽입함으로써 이러한 시스템, 예를 들어, IRES에 의해 TetR에 연결된 TetR의 효율성을 향상시킬 수 있다. 또 다르게는, 원하는 기능에 대한 스크리닝 전에 적어도 3일을 기다릴 수 있다. 이 시스템의 효율성을 향상시키기 위해 공지된 수단에 의해 원하는 단백질의 발현을 향상시킬 수 있다. 예를 들어, Woodchuck Hepatitis Virus Posttranscriptional Regulatory Element (WPRE)를 사용한다.
다른 구체예에서, 이식 유전자에 대한 원래의 프로모터가 사용될 것이다. 본래 프로모터는 이식 유전자의 발현이 본래 발현을 모방하는 것으로 소망될 때 바람직할 수 있다. 원래 프로모터는 이식 유전자의 발현이 일시적으로 또는 발달적으로, 또는 조직-특이적 방법으로, 또는 특이적 전사 자극에 대한 반응으로 조절되어야 할 때, 사용될 수 있다. 추가 구체예에서, 인핸서 요소, 폴리아데닐화 자리 또는 Kozak 일치 서열과 같은 다른 본래 발현 조절 요소는 또한 본래 발현을 모방하도록 사용될 수 있다.
이식 유전자의 다른 구체예는 조직-특이적 프로모터에 작동가능하게 연결된 이식 유전자를 포함한다. 예를 들어, 골격근에서 발현이 소망된다면, 근육에서 활성인 프로모터가 사용되어야 한다. 이들은 골격의 β-액틴, 미오신 경사슬 2A, 디스트로핀, 근육 크레아틴 키나아제를 암호화하는 유전자로부터의 프로모터뿐만 아니라 자연적으로 발생하는 프로모터보다 더 높은 활성을 가지는 합성 근육 프로모터를 포함한다(Li et al ., Nat . Biotech., 17:241-245 (1999)). 조직-특이적인 프로모터의 예는 간(알부민, Miyatake et al , J. Virol , 71 :5124-32 (1997); B형 간염바이러스 코어 프로모터, Sandig et al , Gene Ther ., 3: 1002-9 (1996); 알파-태아 단백질(AFP), Arbuthnot et al ., Hum . Gene Ther ., 7: 1503-14 (1996)), 뼈 오스테오칼신(Stein et al , Mol . Biol . Rep ., 24:185-96 (1997)); 뼈 시알로단백질(Chen et al , J. Bone Miner . Res ., 11:654-64 (1996)), 림프구 (CD2, Hansal et al, J. Immunol, 161:1063-8 (1998); 면역글로불린 중사슬; T 세포 수용체 사슬), 뉴런-특이적 에놀라아제(NSE) 프로모터와 같은 신경세포(Andersen et al , Cell . Mol . Neurobiol, 13:503-15 (1993)), 신경미세섬유 경-사슬 유전자(Piccioli et al , Proc. Natl . Acad . Sci USA, 88:561 1-5 (1991)), 및 특히 뉴런-특이적 vgf 유전자(Piccioli et al , Neuron, 15:373-84 (1995))에 대해 알려져 있다.
선택적으로, 치료적으로 유용한 또는 면역성 생성물을 암호화하는 이식 유전자를 전달하는 벡터는 또한 선택가능한 마커를 포함할 수 있고, 또는 리포터 유전자는 특히 제네티신, 하이그로미신 또는 퓨리마이신 저항을 암호화하는 서열을 포함할 수 있다. 이러한 선택가능한 리포터 또는 마커 유전자(바람직하게는 바이러스 입자안으로 패키징되는 바이러스 게놈 밖에 위치됨)는 암피실린 저항과 같은 박테리아 세포에서 플라스미드의 존재를 표시하는데 사용될 수 있다. 벡터의 다른 성분은 복제의 기원을 포함할 수 있다. 이들 및 다른 프로모터 및 벡터 요소의 선택은 통상적이며 많은 이러한 서열이 이용가능하다[예를 들어, Sambrook et al, 및 그것에 인용된 참고문헌 참조].
이들 벡터는 당업자에게 공지된 기술과 함께, 본원에 제공된 기술 및 서열을 사용하여 발생된다. 이러한 기술은 문헌[Sambrook et al, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Press, Cold Spring Harbor, NY]에서 기술되는 것과 같은 cDNA의 통상적인 클로닝 기술, 아데노바이러스 게놈의 중복 올리고뉴클레오티드 서열의 사용, 폴리머라아제 연쇄 반응, 및 원하는 뉴클레오티드 서열을 제공하는 어떤 적당한 방법을 포함한다.
III
. 바이러스 벡터의 생성
한 구체예에서, 유인원 아데노바이러스 플라스미드(또는 다른 벡터)는 아데노바이러스 벡터를 만드는데 사용된다. 한 구체예에서, 아데노바이러스 벡터는 복제-결함의 아데노바이러스 입자이다. 한 구체예에서, 아데노바이러스 입자는 E1a 및/또는 E1b 유전자에서 결실에 의한 복제-결함이 제공된다. 또 다르게는, 아데노바이러스는, 선택적으로 E1a 및/또는 E1b 유전자를 보유하는 동안 다른 수단에 의한 복제-결함이 제공된다. 아데노바이러스 벡터는 또한 아데노바이러스 게놈에서 다른 돌연변이, 예를 들어, 다른 유전자에서 온도-민감 돌연변이 또는 결실을 함유할 수 있다. 다른 구체예에서, 아데노바이러스 벡터에서 무결함 E1a 및/또는 E1b 영역을 보유하는 것이 바람직하다. 이러한 무결함 E1 영역은 아데노바이러스 게놈에서 그것의 본래 위치에서 위치될 수도 있고 또는 본래 아데노바이러스 게놈에서 결실 자리(예를 들어, E3 영역)에 위치될 수도 있다.
인간(또는 다른 포유동물) 세포에 유전자의 전달을 위해 유용한 유인원 아데노바이러스 벡터의 구성에서, 아데노바이러스 핵산 서열의 범위는 벡터에서 사용될 수 있다. 예를 들어, 모든 또는 일부의 아데노바이러스 지연 초기 유전자 E3은 재조합 바이러스의 부분을 형성하는 유인원 아데노바이러스 서열로부터 제거될 수 있다. 유인원 E3의 기능은 재조합 바이러스 입자의 기능 및 생성에 무관한 것으로 믿어진다. 유인원 아데노바이러스 벡터는 또한 E4 유전자의 적어도 ORF6 영역의 결실을 가지도록, 더 바람직하게는 이 영역, 전체 E4 영역 기능의 불필요한 중복 때문에 구성될 수 있다. 본 발명의 또 다른 벡터는 지연된 초기 유전자 E2a에서 결실을 함유한다. 결실은 또한 유인원 아데노바이러스 게놈의 L5를 통해 어떤 말기 유전자 L1에서 만들어질 수 있다. 유사하게, 중간 유전자 IX 및 IVa2의 결실은 일부 목적에 유용할 수 있다. 다른 결실은 다른 구조적 또는 비-구조적 아데노바이러스 유전자에서 만들어질 수 있다. 상기 논의된 결실은 개개로 사용될 수 있고, 즉, 본원에 설명되는 바와 같은 사용을 위한 아데노바이러스 서열은 단지 단일 영역에서 결실을 함유할 수 있다. 또 다르게는, 전체 유전자 또는 그것의 생물학적 활성을 파괴하는데 효과적인 그것의 부분의 결실은 어떤 조합으로 사용될 수 있다. 예를 들어, 한 예시적인 벡터에서, 아데노바이러스 서열은 E1 유전자 및 E4 유전자, 또는 E1, E2a 및 E3 유전자, 또는 E1 및 E3 유전자, 또는 E3 등의 결실과 함께 또는 결실 없이, E1, E2a 및 E4 유전자의 결실을 가질 수 있다. 상기 논의한 바와 같이, 이러한 결실은 원하는 결과를 이루기 위해 온도-민감 돌연변이와 같은 다른 돌연변이와 조합하여 사용될 수 있다.
어떤 필수 아데노바이러스 서열을 결핍하는 아데노바이러스 벡터(예를 들어, E1a, E1b, E2a, E2b, E4 ORF6, L1, L2, L3, L4 및 L5)는 아데노바이러스 입자의 바이러스 전염력 및 증식에 필요로 되는 비교대상 외 아데노바이러스 유전자 생성물의 존재하에서 배양될 수 있다. 이들 헬퍼 기능은 하나 이상의 헬퍼 구조체(예를 들어, 플라스미드 또는 바이러스) 또는 패키징 숙주 세포의 존재하에서 아데노바이러스 벡터를 배양함으로써 제공될 수 있다. 예를 들어, 1996년 5월 9일 공개되고, 본원에 참고로써 포함된 국제 특허 출원 WO96/13597의 "최소의" 인간 Ad 벡터의 제조에 대해 설명된 기술을 참조.
1.
헬퍼
바이러스
따라서, 미니유전자을 전달하는데 사용되는 바이러스 벡터의 유인원 아데노바이러스 유전자 함량에 의존하여, 헬퍼 아데노바이러스 또는 비-복제 바이러스 단편이 미니유전자를 함유하는 감염 재조합 바이러스 입자를 생성하는데 필요한 충분한 유인원 아데노바이러스 유전자 서열을 제공하기 위해 필요할 수 있다. 유용한 헬퍼 바이러스는 아데노바이러스 벡터 구조체에서 존재하지 않는 및/또는 벡터가 트랜스펙팅되는 패키징 셀 라인에 의해 발현되지 않는 선택된 아데노바이러스 유전자 서열을 함유한다. 한 구체예에서, 헬퍼 바이러스는 복제-결함이며, 상기 기술된 서열에 더하여 다양한 아데노바이러스 유전자를 함유한다. 이러한 헬퍼 바이러스는 E1-발현 셀 라인과 조합하여 바람직하게 사용된다.
헬퍼 바이러스는 또한 Wu et al , J. Biol . Chem ., 264:16985-16987 (1989); K. J. Fisher 및 J. M. Wilson, Biochem. J., 299:49 (1994년 4월 1일)에서 기술된 바와 같은 폴리-양이온 콘쥬게이트로 형성될 수 있다. 헬퍼 바이러스는 선택적으로 제 2 리포터 미니유전자를 함유할 수 있다. 다수의 이러한 리포터 유전자는 당업계에 공지되어 있다. 아데노바이러스 벡터에서 이식 유전자와 다른 헬퍼 바이러스 상의 리포터 유전자의 존재는 독립적으로 모니터링되는 Ad 벡터와 헬퍼 바이러스 둘 다를 허용한다. 이런 제 2 리포터는 정제 시 결과 재조합 바이러스와 헬퍼 바이러스 사이의 분리를 가능하게 하는데 사용된다.
2. 상보성 셀 라인
상기 기술된 어떤 유전자에서 결실된 재조합 유인원 아데노바이러스(Ad)를 발생시키기 위해, 바이러스의 복제 및 전염력에 필수적이라면, 결실된 유전자 영역의 기능은 헬퍼 바이러스 또는 셀 라인, 즉, 상보성 또는 패키징 셀 라인에 의해 재조합 바이러스에 공급되어야 한다. 많은 환경에서, 인간 E1을 발현시키는 셀 라인은 침팬지 Ad 벡터를 서로 보완하기 위해 사용될 수 있다. 본 발명의 침팬지 Ad 서열과 현재 이용가능한 패키징 세포에서 발견되는 인간 AdE1 서열 사이의 다양성에 기인하여, 현재 인간 E1-함유 세포의 사용이 복제 및 생성 과정 동안 복제-가능 아데노바이러스의 생성을 방지하기 때문에 이는 특히 유리하다. 그러나, 특정 환경에서, E1 유전자 생성물을 발현시키고 E1-결핍 유인원 아데노바이러스의 생성에 이용될 수 있는 셀 라인을 이용하는 것이 바람직할 것이다. 이러한 셀 라인은 기술되었다. 예를 들어, 미국 특허 6,083,716호 참조.
원한다면, 선택된 모 셀 라인에서 발현을 위한 프로모터의 전사 조절 하에서 SAdV28로부터 아데노바이러스 E1 유전자를 최소한으로 발현시키는 패키징 세포 또는 셀 라인을 발생시키기 위해 본원에 제공되는 서열을 이용할 수 있다. 유도성 또는 구성적 프로모터는 이 목적을 위해 사용될 수 있다. 이러한 프로모터의 예는 본 명세서의 어디에서나 상세하게 설명된다. 모 세포는 어떤 요망되는 SAdV28 유전자를 발현시키는 신규 셀 라인의 생성을 위해 선택된다. 제한 없이, 이러한 모 셀 라인은 특히 HeLa [ATCC Accession No. CCL 2], A549 [ATCC Accession No. CCL 185], HEK 293, KB [CCL 17], Detroit [예를 들어, Detroit 510, CCL 72] 및 WI-38 [CCL 75] 세포일 수 있다. 이들 셀 라인은 모두 American Type Culture Collection, 10801 University Boulevard, Manassas, Virginia 20110-2209로부터 이용가능하다. 다른 적당한 모 셀 라인은 다른 공급원으로부터 획득될 수 있다.
이러한 E1-발현 셀 라인은 재조합 유인원 아데노바이러스 E1 결실 벡터의 생성에서 유용하다. 추가적으로, 또 다르게는, 하나 이상의 유인원 아데노바이러스 유전자 생성물, 예를 들어, E1a, E1b, E2a, 및/또는 E4 ORF6을 발현시키는 셀 라인은 재조합 유인원 바이러스 벡터의 생성에서 사용되는 바와 같은 본질적으로 동일한 과정을 사용하여 구성될 수 있다. 이러한 셀 라인은 그런 생성물을 암호화하는 필수적 유전자에서 결실된 아데노바이러스를 서로보완하기 위해, 또는 헬퍼-의존 바이러스(예를 들어, 아데노-관련 바이러스)의 패키징에 필요한 헬퍼 기능을 제공하기 위해 이용될 수 있다. 숙주 세포의 제조는 선택된 DNA 서열의 조합과 같은 기술을 수반한다. 이 조합은 통상적인 기술을 이용하여 수행될 수 있다. 이러한 기술은 폴리머라아제 연쇄 반응, 합성 방법, 및 원하는 뉴클레오티드 서열을 제공하는 어떤 다른 적당한 방법과 조합된, 잘 공지되어 있고 상기 인용한 Sambrook et al.에서 기술되는 cDNA 및 게놈 클로닝, 아데노바이러스 게놈의 중복 올리고뉴클레오티드 서열의 사용을 포함한다.
또 다른 대안으로, 필수적인 아데노바이러스 유전자 생성물이 아데노바이러스 벡터 및/또는 헬퍼 바이러스에 의해 트랜스에서 제공된다. 이러한 예에서, 적절한 숙주 세포는 원핵(예를 들어, 박테리아) 세포를 포함하는 어떤 생물학적 유기체, 및 곤충 세포, 효모 세포 및 포유동물 세포를 포함하는 진핵세포로부터 선택될 수 있다. 특히 바람직한 숙주 세포는, 제한 없이, A549, WEHI, 3T3, 10T1/2, HEK 293 세포 또는 PERC6 (이들 둘 다 기능적 아데노바이러스 E1을 발현시킨다) [Fallaux, FJ et al, (1998), Hum Gene Ther, 9:1909-1917], Saos, C2C12, L 세포, HT1080, HepG2 및 일차 섬유아세포, 인간, 원숭이, 마우스, 래트, 토끼 및 햄스터를 포함하는 포유동물로부터 유래된 간세포 및 근원세포와 같은 세포를 포함하는 어떤 포유동물 종 중에서 선택된다. 세포를 제공하는 포유동물 종의 선택은 본 발명을 제한하지 않으며; 포유동물 세포, 즉, 섬유아세포, 간세포, 종양 세포 등의 종류도 아니다.
3. 셀 라인의 바이러스 입자 및
트랜스펙션의
조합
일반적으로, 트랜스펙션에 의해 미니유전자를 포함하는 벡터를 전달할 때, 벡터는 약 1 x 104 세포 내지 약 1 x 1013 세포, 및 바람직하게는 약 105 세포에서 약 5 μg 내지 약 100 μg DNA, 및 바람직하게는 약 10 내지 약 50 μg DNA의 양으로 전달된다. 그러나, 선택된 벡터, 전달 방법 및 선택된 숙주 세포로서 고려하여, 숙주 세포에서 벡터 DNA의 상대적 양은 조절될 수 있다.
벡터는 네이키드 DNA, 플라스미드, 파지, 트랜스포존, 코스미드, 에피솜, 바이러스 등을 포함하여 당업계에 알려진 또는 상기 기재된 어떤 벡터일 수 있다. 벡터의 숙주 세포에 도입은 트랜스펙션, 및 감염을 포함하는 당업계에 공지된 또는 상기 기재된 바와 같은 어떤 수단에 의해 달성될 수 있다. 하나 이상의 아데노바이러스 유전자는 숙주 세포의 게놈에 안정적으로 통합되고, 에피솜으로서 안정적으로 발현되고, 또는 일시적으로 발현될 수 있다. 유전자 생성물은 모두 에피솜에서 일시적으로 발현되거나 안정적으로 통합될 수 있고, 또는 유전자 생성물의 일부는 안정적으로 발현되는 반면, 나머지는 일시적으로 발현될 수도 있다. 추가로, 각각의 아데노바이러스 유전자의 프로모터는 구성적 프로모터, 유도성 프로모터 또는 본래 아데노바이러스 프로모터로부터 독립적으로 선택될 수 있다. 프로모터는 예를 들어, 유기체 또는 세포의 특이적 생리학적 상태에 의해(즉, 분화상태에 의해 또는 복제 또는 정지 세포(quiescent cell)에서) 또는 외인성으로-첨가된 인자에 의해 조절될 수 있다.
숙주 세포에 분자(플라스미드 또는 바이러스)의 도입은 또한 당업자에게 공지되고, 본 명세서를 통해 논의되는 바와 같은 기술을 사용하여 수행될 수 있다. 바람직한 구체예에서, 표준 트랜스펙션 기술, 예를 들어, CaPO4 트랜스펙션 또는 전기천공법이 사용된다.
재조합 바이러스 입자를 생성하기 위해 아데노바이러스의 선택된 DNA 서열뿐만 아니라 이식 유전자 및 다른 벡터 요소의 다양한 중간체 플라스미드에의 조합, 및 플라스미드 및 벡터의 사용은 통상적인 기술을 사용하여 모두 달성된다. 이러한 기술은 문헌[Sambrook et al, 상기 인용]에서 기술되는 것과 같은 cDNA의 통상적인 클로닝 기술, 아데노바이러스 게놈의 중복 올리고뉴클레오티드 서열의 사용, 폴리머라아제 연쇄 반응, 및 원하는 뉴클레오티드 서열을 제공하는 어떤 적당한 방법을 포함한다. 표준 트랜스펙션 및 공동-트랜스펙션 기술, 예를 들어, CaPO4 침지 기법이 사용된다. 사용되는 다른 통상적인 방법은 바이러스 게놈의 상동 재조합, 한천중층에서 바이러스의 플라크, 신호 생성을 측정하는 방법 등을 포함한다.
예를 들어, 원하는 미니유전자-함유 바이러스 벡터의 구성 및 조합에 따라서, 벡터는 헬퍼 바이러스의 존재하에서 패키징 셀 라인 안으로 시험관 내에서 트랜스펙팅된다. 상동 재조합은 헬퍼와 벡터 서열 사이에서 발생하며, 이는 비리온 캡시드로 복제되고 패키징되는 벡터에서 아데노바이러스-이식 유전자 서열을 허용하여, 재조합 바이러스 벡터 입자를 초래한다. 이러한 바이러스 입자를 생성하는 현재의 방법은 트랜스펙션에 기초한다. 그러나, 본 발명은 이러한 방법에 제한되지 않는다.
결과 재조합 유인원 아데노바이러스는 선택된 이식 유전자가 선택된 세포로 이동하는데 유용하다. 패키징 셀 라인에서 성장한 재조합 바이러스에 의한 생체내 실험에서, 본 발명의 E1-결실 재조합 유인원 아데노바이러스 벡터는 이식 유전자를 비-유인원, 바람직하게는 인간, 세포에 이동시키는데 유용함을 증명한다.
IV
. 재조합
아데노바이러스
벡터의 사용
재조합 유인원 아데노바이러스-40, SAdV-31 또는 SAdV-34 기초 벡터는 시험관내, 생체 밖, 및 생체 내 인간 또는 비-유인원 수의과 환자에서 유전자 전달에 유용하다.
본원에 설명되는 재조합 아데노바이러스 벡터는 시험관내 이종성 유전자에 의해 암호화되는 생성물의 생성을 위한 발현 벡터로서 사용될 수 있다. 예를 들어, E1 결실의 위치로 삽입되는 유전자를 함유하는 재조합 아데노바이러스는 상기 기술한 바와 같은 E1-발현 셀 라인에 트랜스펙팅될 수 있다. 또 다르게는, 복제-가능 아데노바이러스는 다른 선택된 셀 라인에서 사용될 수 있다. 트랜스펙팅된 세포는 그 후 통상적인 방법으로 배양되고, 프로모터로부터 유전자 생성물을 발현시키기 위한 재조합 아데노바이러스를 허용한다. 유전자 생성물은 그 후 배양물로부터 단백질 분리 및 회수의 공지된 통상적인 방법에 의해 배양물 배지로부터 회수될 수 있다.
SAdV-40, SAdV-31 또는 SAdV-34-유래 재조합 유인원 아데노바이러스 벡터는 생체내 또는 생체밖에서 조차 선택되는 숙주 세포에 선택된 이식 유전자를 전달할 수 있는 효율적인 유전자 전달 비히클을 제공하며, 유기체는 하나 이상의 AAV 항원형에서 중화 항체를 가진다. 한 구체예에서, rAAV 및 세포는 생체밖에서 혼합되고; 감염 세포는 통상적인 방법을 사용하여 배양되며; 형질도입된 세포는 환자에 재주입된다. 이들 조성물은 치료적 목적 및 보호 면역을 유발하는 것을 포함하는 면역을 위한 유전자 전달에 특히 적합하다.
더 흔하게는, SAdV-40, SAdV-31 또는 SAdV-34 재조합 아데노바이러스 벡터는 하기 기술되는 바와 같은 치료 또는 면역 분자의 전달을 위해 이용될 것이다. 본 발명의 재조합 아데노바이러스 벡터는 재조합 아데노바이러스 벡터의 반복 전달을 수반하는 요법에서 사용에 특히 적합하다는 것이 두 용도에 대해 용이하게 이해될 것이다. 이러한 요법은 전형적으로 바이러스 캡시드가 변형되는 일련의 바이러스 벡터의 전달을 수반한다. 바이러스 캡시드는 각각의 이후의 투여를 위해, 또는 특정 항원형 캡시드의 미리-선택된 수(예를 들어, 1, 2, 3, 4 또는 그 이상)의 투여 후 변형될 수 있다. 따라서, 요법은 제 1 유인원 캡시드와 함께 rAd의 전달, 제 2 유인원 캡시드와 함께 rAd의 전달, 및 제 3 유인원 캡시드와 함께 전달을 수반할 수 있다. 본 발명의 Ad 캡시드를 단독으로, 다른 것과 조합하여, 또는 다른 아데노바이러스와 조합하여(바람직하게는 면역적으로 비-교차반응임) 사용하는 다양한 다른 요법은 당업자에게 명백할 것이다. 선택적으로, 이러한 요법은 다른 비-인간 영장류 아데노바이러스, 인간 아데노바이러스, 또는 본원에 설명되는 것과 같은 인공 서열의 캡시드와 함께 rAd의 투여를 수반할 수 있다. 요법의 각 단계는 단일 Ad 캡시드로 일련의 주입(또는 다른 전달 경로) 후 다른 Ad 공급원으로부터 일련의 다른 캡시드의 투여를 수반할 수 있다. 또 다르게는, SAdV-40, SAdV-31 또는 SAdV-34 벡터는 다른 바이러스 시스템, 비-바이러스 전달 시스템, 단백질, 펩티드, 및 다른 생물학적으로 활성인 분자를 포함하는 다른 비-아데노바이러스-매개 전달 시스템을 수반하는 요법에서 이용될 수 있다.
하기의 섹션은 본 발명의 아데노바이러스 벡터를 통해 전달될 수 있는 예시적인 분자에 초점을 맞출 것이다.
A. 치료 분자의
Ad
-매개 전달
한 구체예에서, 상기-기술된 재조합 벡터는 유전자 치료를 위해 공개된 방법에 따라서 인간에 투여된다. 선택된 이식 유전자를 함유하는 유인원 바이러스 벡터는 환자에 투여될 수 있으며, 바람직하게는 생물학적으로 양립가능한 용액 또는 약학적으로 허용가능한 전달 비히클에서 현탁된다. 적당한 비히클은 멸균 식염수를 포함한다. 약학적으로 허용가능한 담체로 공지되고 당업자에게 잘 알려진 다른 수성 및 비-수성 등장 멸균 주사 용액 및 수성 및 비-수성 멸균 현탁액은 본 목적을 위해 사용될 수 있다.
유인원 아데노바이러스 벡터는 표적 세포를 형질도입하고 유전자 전달 및 발현의 충분한 수준을 제공하는데 충분한 양으로 투여되어, 지나친 불리함 없이 또는 의학적으로 허용가능한 생리적인 효과와 함께 치료적 이점을 제공하며, 이는 의학 분야의 당업자에 의해 결정될 수 있다. 투여의 통상적인 및 약학적으로 허용가능한 경로는, 제한되는 것은 아니지만, 망막에 직접적인 전달 및 다른 안구 전달 방법, 간에 직접적인 전달, 흡입, 비강내, 정맥내, 근육내, 기관내, 피하, 피내, 직장, 경구 및 다른 비경구 투여 경로를 포함한다. 투여 경로는, 원한다면, 이식 유전자 또는 질환에 따라서 조합 또는 조절될 수 있다. 투여 경로는 주로 치료되는 질환의 특성에 의존할 것이다.
바이러스 벡터의 투약은 치료되는 질환, 환자의 연령, 체중 및 건강상태와 같은 요인에 주로 의존할 것이고, 따라서 환자들 사이에서 다양할 수 있다. 예를 들어, 바이러스 벡터의 치료적으로 유효한 성인 인간 또는 수의과 투약량은 일반적으로 약 1 x 106 내지 약 1 x 1015 입자, 약 1 x 1011 내지 1 x 1013 입자, 또는 약 1 x 109 내지 1 x 1012 입자 바이러스의 농도를 함유하는 담체의 약 100 μL 내지 약 100 mL의 범위에 있다. 투약량은 동물의 크기 및 투여 경로에 의존하는 범위에 있을 것이다. 예를 들어, 근육내 주사에 대해 적당한 인간 또는 수의적 투약량(약 80 kg 동물)은 단일 자리에 대해 mL 당, 약 1 x 109 내지 약 5 x 1012 입자의 범위에 있다. 선택적으로, 투여의 다양한 자리는 전달될 수 있다. 다른 예에서, 적당한 인간 또는 수의적 투여는 경구 제형에 대해 약 1 x 1011 내지 약 1 x 1015 입자의 범위에 있을 수 있다. 당업자는 투여 경로, 및 재조합 벡터가 사용되기 위한 치료 또는 백신 용도에 따라서 이들 용량을 조절할 수 있다. 이식 유전자의 발현 수준, 또는 면역원, 순환 항체의 수준은 투약량 투여의 빈도를 결정하기 위해 모니터링 될 수 있다. 투여 빈도의 시간을 결정하기 위한 또 다른 방법은 당업자에게 용이하게 명백할 것이다.
선택적 방법 단계는 바이러스 벡터의 투여와 동시에, 또는 전 또는 후에 적당한 양의 짧은 작동 면역 조절자의 환자에서 공동-투여를 수반한다. 선택된 면역 조절자는 본 발명의 재조합 벡터에 대해 관련된 중화 항체의 형성을 억제할 수 있는 또는 벡터의 T 림프구 (CTL) 제거를 억제할 수 있는 약제로서 본원에 정의된다. 면역 조절자는 T 헬퍼 서브셋(TH1 또는 TH2)과 B 세포 사이에서 상호작용을 방해하여 중화 항체 형성을 억제할 수 있다. 또 다르게는, 면역 조절자는 TH1 세포와 CTL 사이의 상호작용을 억제하여 벡터의 CTL 제거의 발생을 감소시킬 수 있다. 다양한 유용한 면역 조절자 및 그것의 사용을 위한 투약량은, 예를 들어, Yang et al ., J. Virol., 70(9) (Sept., 1996); 1996년 5월 2일 공개된 국제 특허 출원 번호 WO96/12406; 및 본원에 모두 참고로써 포함되는 국제 특허출원 번호 PCT/US96/03035에서 개시된다.
1. 치료 이식 유전자
이식 유전자에 의해 암호화되는 유용한 치료적 생성물은, 제한 없이, 인슐린, 글루카곤, 성장 호르몬(GH), 파라티로이드 호르몬(PTH), 성장 호르몬 방출 인자(GRF), 여포 자극 호르몬(FSH), 황체 형성 호르몬(LH), 인간 융모성 고나도트로핀(hCG), 혈관내피성장인자(VEGF), 엔지오포이에틴, 엔지오스태틴, 백혈구조혈성장인자 (GCSF), 에리스로포이에틴(EPO), 결합조직 성장인자(CTGF), 염기성 섬유아세포 성장인자 (bFGF), 산성 섬유아세포 성장인자(aFGF), 상피세포성장인자(EGF), 형질전환 성장인자 (TGF), 혈소판 유래 성장인자 (PDGF), 인슐린 성장 인자 1 및 II (IGF-I 및 IGF-II), TGF, 액티빈, 인히빈을 포함하는 형질전환 성장 인자 수퍼패밀리의 어떤 하나, 또는 어떤 뼈 형성 단백질(BMP) BMPs 1-15, 성장 인자의 헤레귤인/뉴레귤린/ARIA/neu 분화 인자(NDF) 패밀리 중 어떤 하나, 신경 성장인자(NGF), 뇌-유래 신경 친화성 인자(BDNF), 뉴로트로핀 NT-3 및 NT-4/5, 섬모 향신경성 인자(CNTF), 신경아교세포계 유래 신경영양 인자(GDNF), 뉴투린, 애그린, 세마포린/콜랩신의 패밀리 중 어떤 하나, 네트린-1 및 네트린-2, 간세포성장인자(HGF), 에프린, 노긴, 소닉 헤지호그 및 티로신 히드록실라아제를 포함하는 호르몬 및 성장 및 분화 인자를 포함한다.
다른 유용한 이식 유전자 생성물은, 제한 없이, 사이토카인 및 림포카인, 예로써, 트롬보포이에틴(TPO), IL-25를 통한 인터류킨(IL) IL-1(예를 들어, IL-2, IL-4, IL-12 및 IL-18을 포함), 단핵세포 화학유인물질 단백질, 백혈병 억제 인자, 과립성 백혈구 - 대식세포 집락 자극인자, 파스(Fas) 리간드, 종양 괴사 인자 및, 인터페론, 및 줄기 세포 인자, flk-2/flt3 리간드를 포함하는 면역 체계를 조절하는 단백질을 포함한다. 면역 체계에 의해 생성되는 유전자 생성물은 또한 본 발명에 유용하다. 이들은, 제한 없이, 면역글로불린 IgG, IgM, IgA, IgD 및 IgE, 키메라 면역글로불린, 인간화된 항체, 단일쇄 항체, T 세포 수용체, 키메라 T 세포 수용체, 단일쇄 T 세포 수용체, 클래스 I 및 클래스 II MHC 분자, 및 공학변형된 면역글로불린 및 MHC 분자를 포함한다. 유용한 유전자 생성물은 또한 상보적 조절 단백질, 막 보조 단백질(MCP), 붕괴 촉진인자(DAF), CR1, CF2 및 CD59를 포함한다.
또 다른 유용한 유전자 생성물은 호르몬, 성장 인자, 사이토카인, 림포카인, 조절 단백질 및 면역 체계 단백질에 대한 수용체 중 어떤 하나를 포함한다. 본 발명은 저밀도 리포단백질(LDL) 수용체, 고밀도 리포단백질(HDL) 수용체, 매우 낮은 밀도 리포단백질(VLDL) 수용체, 및 스캐빈저 수용체를 포함하는 콜레스테롤 조절을 위한 수용체를 포함한다. 본 발명은 또한 글루코코르티코이드 수용체 및 에스트로겐 수용체, 비타민 D 수용체 및 다른 핵 수용체를 포함하는 스테로이드 호르몬 수용체 수퍼패밀리의 멤버와 같은 유전자 생성물을 포함한다. 게다가, 유용한 유전자 생성물은 전사 인자, 예컨대, jun , fos, max, mad, 혈청반응인자(SRF), AP-1, AP2, myb, MyoD 및 마이오제닌, ETS-박스 함유 단백질, TFE3, E2F, ATF1, ATF2, ATF3, ATF4, ZF5, NFAT, CREB, HNF-4, C/EBP, SP1, CCAAT-박스 결합 단백질, 인터페론 조절 인자 (IRF-1), 윌름 종양 단백질, ETS-결합 단백질, STAT, GATA-박스 결합 단백질, 예컨대, GATA-3, 및 날개달린(winged) 나선형 단백질의 포크헤드(forkhead) 패밀리를 포함한다.
다른 유용한 생성물은, 카르바모일 합성효소 I, 오르니틴 트랜스카르바밀라아제, 아르기노숙시네이트 합성효소, 아르기노숙시네이트 리아제, 아르기나아제, 푸마릴아세트아세테이트 가수분해효소, 페닐알라닌 가수분해효소, 알파-1 안티트립신, 글루코오스-6-포스페이트, 포르포빌리노겐 디아미나아제, 인자 VIII, 인자 IX, 시스타티온 베타-합성효소, 가지사슬 케토산 데카르복실라아제, 알부민, 이소발레릴-coA 탈수소효소, 프로피오닐 CoA 카르복실라아제, 메틸 말로닐 CoA 무타아제, 글루타릴 CoA 탈수소효소, 인슐린, 베타-글루코시다아제, 파이루베이트 카르복실레이트, 간 포스포릴라아제, 포스포릴라아제 키나아제, 글리신 데카르복실라아제, H-단백질, T-단백질, 낭포성 섬유증 막단백질 조절자(CFTR) 서열, 및 디스트로핀 cDNA 서열을 포함한다.
다른 유용한 유전자 생성물은 비-천연적으로 발생하는 폴리펩티드, 예컨대, 삽입, 결실 또는 아미노산 치환을 함유하는 비-천연적으로 발생하는 아미노산 서열을 가지는 키메라 또는 하이브리드 폴리펩티드를 포함한다. 예를 들어, 단일-사슬 공학변형된 면역글로불린은 특정 면역타협 환자에서 유용할 수 있다. 비-천연적으로 발생하는 유전자 서열의 다른 종류는 표적의 과발현을 감소시키는데 사용될 수 있는 안티센스 분자 및 촉매적 핵산, 예를 들어 리보자임을 포함한다.
유전자 발현의 감소 및/또는 조절은 암 및 건선과 같이 이상증식 세포를 특징으로 하는 이상증식 질환의 치료에 특히 바람직하다. 표적 폴리펩티드는 정상 세포와 비교하여 이상증식 세포에서 배타적으로 또는 더 높은 수준으로 생성되는 폴리펩티드를 포함한다. 표적 항원은 myb, myc, fyn, 및 전좌 유전자 bcr/abl, ras, src, P53, neu, trk 및 EGRF과 같은 종양유전자에 의해 암호화되는 폴리펩티드를 포함한다. 표적 항원으로서 종양유전자 생성물에 더하여, 항-암 치료를 위한 표적 폴리펩티드 및 보호 요법은 B 세포 림프종에 의해 만들어지는 항체의 가변 영역 및 T 세포 림프종의 T 세포 수용체의 가변 영역을 포함하며, 일부 구체예에서, 이는 또한 자가면역 질병에 대한 표적 항원으로서 사용된다. 다른 종양-관련 폴리펩티드는 모노클로날 항체 17-1A 및 폴레이트 결합 폴리펩티드에 의해 인식되는 폴리펩티드를 포함하는 종양 세포에서 더 높은 수준으로 발견되는 폴리펩티드와 같은 표적 폴리펩티드로서 사용될 수 있다.
다른 적당한 치료 폴리펩티드 및 단백질은 세포 수용체 및 자기-관련 항체를 생성하는 세포를 포함하는 자가면역과 관련된 표적에 대하여 광범위 기초 보호 면역 반응을 부여함으로써 자가면역 질병 및 장애를 겪고 있는 개체를 치료하는데 유용할 수 있는 것들을 포함한다. T 세포 매개 자가면역 질병은 류마티스 관절염(RA), 다발성경화증(MS), 쇼그렌증후군, 유육종증, 인슐린 의존성 당뇨병(IDDM), 자가면역성 갑상샘염, 반응성 관절염, 강직성 척추염, 경피증, 다발성 근염, 건선, 혈관염, 베게너 육아종증, 크론병 및 궤양성 대장염을 포함한다. 각각의 이들 질병은 내인성 항원에 결합하고 자가면역 질병에 관련되는 면역 캐스캐이드를 시작하는 T 세포 수용체(TCR)를 특징으로 한다.
본 발명의 유인원 아데노바이러스 벡터는 특히 이식 유전자의 다양한 아데노바이러스-매개 전달이 요망되는 치료 요법에서, 예를 들어, 동일한 이식 유전자의 회복을 수반하는 요법에서 또는 다른 이식 유전자의 전달을 수반하는 요법과 조합하여 적합하다. 이러한 요법은 SAdV-40, SAdV-31 또는 SAdV-34 유인원 아데노바이러스 벡터의 투여 후, 동일한 항원형 아데노바이러스로부터의 벡터와 함께 재-투여를 수반할 수 있다. 특히 바람직한 요법은 SAdV-40, SAdV-31 또는 SAdV-34 유인원 아데노바이러스 벡터의 투여를 수반하며, 제 1 투여로 전달되는 벡터의 아데노바이러스 캡시드 서열의 공급원은 하나 이상의 이후의 투여에서 이용되는 바이러스 벡터의 아데노바이러스 캡시드 서열의 공급원과 다르다. 예를 들어, 치료 요법은 SAdV-40, SAdV-31 또는 SAdV-34 벡터의 투여 및 동일 또는 다른 항원형의 하나 이상의 아데노바이러스 벡터에 의한 반복 투여를 수반한다. 다른 예에서, 치료 요법은 아데노바이러스 벡터의 투여 후 제 1 전달 아데노바이러스 벡터에서 캡시드의 공급원과 다른 캡시드를 가지는 SAdV-40, SAdV-31 또는 SAdV-34 벡터에 의한 반복 투여, 및 선택적으로 투여 단계 전 벡터의 아데노바이러스 캡시드의 공급원과 동일한 또는, 바람직하게는 다른, 벡터에 의한 투여를 수반한다. 이들 요법은 SAdV-40, SAdV-31 또는 SAdV-34 유인원 서열을 사용하여 구성되는 아데노바이러스 벡터의 전달에 제한되지 않는다. 오히려, 이들 요법은, 제한 없이, 하나 이상의 SAdV-40, SAdV-31 또는 SAdV-34 벡터와 조합하여, 다른 유인원 아데노바이러스 서열(예를 들어, Pan9 또는 C68, C1, 등), 다른 비-인간 영장류 아데노바이러스 서열, 또는 인간 아데노바이러스 서열을 포함하는 다른 아데노바이러스 서열을 용이하게 이용할 수 있다. 이러한 유인원, 다른 비-인간 영장류 및 인간 아데노바이러스 항원형의 예는 본 문서에서 어디에서나 논의된다. 추가로, 이 치료 요법은 비-아데노바이러스 벡터, 비-바이러스 벡터, 및/또는 다양한 다른 치료적으로 유용한 화합물 또는 분자와 조합하여 SAdV-40, SAdV-31 또는 SAdV-34 아데노바이러스 벡터의 자발적 또는 순차적 전달을 수반할 수 있다. 본 발명은 이들 치료 요법에 제한되지 않으며, 다양한 것들이 당업자에게 용이하게 명확할 것이다.
B. 면역성 이식 유전자의
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-매개 전달
재조합 SAdV-40, SAdV-31 또는 SAdV-34 벡터는 또한 면역성 조성물로서 사용될 수 있다. 본원에 사용된 바와 같이, 면역성 조성물은 체액(예를 들어, 항체) 또는 세포(예를 들어, 세포독성 T 세포) 반응이 포유동물, 및 바람직하게는 영장류에 전달 후 면역성 조성물에 의해 전달되는 이식 유전자 생성물에 고정되는 조성물이다. 재조합 유인원 Ad는 원하는 면역원을 암호화하는 그것의 아데노바이러스 서열 결실 유전자 중 어떤 것을 함유할 수 있다. 유인원 아데노바이러스는 인간 기원의 아데노바이러스와 비교하여 다른 동물 종에서 살아있는 재조합 바이러스 백신으로서 사용에 더 적합할 가능성이 있지만, 이러한 사용에 제한되는 것은 아니다. 재조합 아데노바이러스는 면역 반응의 유발에 결정적이고 병원체의 확산을 제한할 수 있다는 것이 확인된 항원(들)에 대한 어떤 병원체 및 cDNA에 대해 이용가능한 어떤 병원체에 대하여 예방 또는 치료 백신으로서 사용될 수 있다.
이러한 백신(또는 다른 면역원) 조성물은 상기 기술한 바와 간은 적당한 전달 비히클에서 제형화된다. 일반적으로 면역성 조성물에 대한 용량은 치료 조성물에 대해 상기 정의한 범위에 있다. 선택 유전자의 면역의 수준은, 만약에 있다면, 부스터에 대한 필요를 결정하기 위해 모니터링될 수 있다. 혈청에서 항체 타이터의 평가에 따라서, 선택적인 부스터 면역이 요망될 수 있다.
선택적으로, 본 발명의 백신 조성물은, 예를 들어, 보조제, 안정화제, pH 조절제, 보존제 등을 포함하는 다른 성분을 함유하기 위해 제형화될 수 있다. 이러한 성분은 백신 업계에서 당업자에게 잘 공지되어 있다. 적당한 보조제의 예는, 제한없이, 리포좀, 알륨, 모노포스포릴 지질 A, 및 어떤 생물학적으로 활성인 인자, 예로써, 사이토카인, 인터류킨, 케모킨, 리간드 및 최상으로는 그것의 조합을 포함한다. 특정의 이들 생물학적으로 활성인 인자는 생체내, 예를 들어, 플라스미드 또는 바이러스 벡터를 통해 발현될 수 있다. 예를 들어, 이러한 보조제는 항원만을 암호화하는 DNA 백신과 함께 프라이밍 시 발생되는 면역 반응과 비교하여, 항원-특이적 면역 반응을 향상시키기 위해 항원을 암호화하는 프라이밍 DNA 백신과 함께 투여될 수 있다.
재조합 아데노바이러스는 "면역원 양", 즉, 원하는 세포를 트랜스펙팅하기 위해 투여되는 경로에서 효과적이고, 면역 반응을 유발하기 위해 선택되는 유전자의 발현의 충분한 수준을 제공하는 양으로 투여된다. 보호 면역이 제공되는 경우, 재조합 아데노바이러스는 감염 및/또는 재발을 예방하는데 유용한 백신 조성물이 되는 것으로 고려된다.
또 다르게는, 또는 추가로, 본 발명의 벡터는 선택된 면역원에 대한 면역 반응을 유발하는 펩티드, 폴리펩티드 또는 단백질을 암호화하는 이식 유전자를 함유한다. 재조합 SAdV 벡터는 벡터에 의해 발현되는 삽입된 이종성 항원 단백질에서 세포 용해 T 세포 및 항체를 유발할 때 매우 효율적인 것으로 기대된다.
예를 들어, 면역원은 다양한 바이러스 과로부터 선택될 수 있다. 면역 반응이 바람직한 바이러스 패밀리의 예는, 보통 감기의 약 50%의 경우를 초래하는 리노바이러스 속; 폴리오바이러스, 콕사키 바이러스, 에코바이러스 및 A형 간염 바이러스와 같은 인간 엔테로바이러스를 포함하는 엔테로바이러스 속; 및 주로 비-인간 동물에서 발 및 구강 질병을 초래하는 압소바이러스 속을 포함하는 피코르나바이러스 과를 포함한다. 바이러스의 피코르나바이러스 과 내에서, 표적 항원은 VP1, VP2, VP3, VP4, 및 VPG를 포함한다. 다른 바이러스 과는 바이러스의 노워크(Norwalk) 군을 포함하고, 유행성 위장염의 중요한 감염인자인 칼시바이러스 과를 포함한다. 인간 및 비-인간 동물에서 면역 반응을 유발하기 위한 표적 항원에서 사용에 바람직한 또 다른 바이러스 과는 토가바이러스 과이며, 이는 신드비스 바이러스, 로스리버 바이러스 및 베네수엘라, 동부형&서부형 마뇌염, 및 루벨라 바이러스를 포함하는 루비바이러스를 포함하는 알파바이러스 속을 포함한다. 플라비비리다에과는 뎅기열, 황열, 일본 뇌염, 세인트루이스 뇌막염 및 진드기매개 바이러스를 포함한다. 다른 표적 항원은 C형 간염 또는 코로나바이러스과로부터 발생될 수 있으며, 이는 다수의 비-인간 바이러스, 예컨대, 전염성 기관지염(가금류), 돼지 전염성 위장염 바이러스(돼지), 돼지 혈구응집성 뇌척수염 바이러스(돼지), 고양이 전염성 복막염 바이러스(고양이), 고양이 장 코노나바이러스(고양이), 개 코로나바이러스(개), 및 인간 호흡 코로나바이러스를 포함하며, 이는 보통의 감기 및/또는 비-A, B 또는 C형 간염을 야기할 수 있다. 코로나바이러스과 내에서, 표적 항원은 E1 (또한 M 또는 매트릭스 단백질로 불림), E2 (또한 S 또는 스파이크 단백질로 불림), E3 (또한 HE 또는 헤마그글루틴-엘터로오스로 불림) 글리코단백질(모든 코로나바이러스에 존재하지 않음) 또는 N(뉴클레오캡시드)을 포함한다. 또 다른 항원은 베시큘로바이러스속(예를 들어, 소수포형 구내염 바이러스), 및 리사 바이러스속(예를 들어, 광견병)을 포함하는 랩도 바이러스과를 표적으로 할 수 있다.
랩도바이러스 과 내에서, 적당한 항원은 G 단백질 또는 N 단백질로부터 유래될 수 있다. 마르부르크 및 에볼라 바이러스와 같은 출혈열 바이러스를 포함하는 필로바이러스 과는 항원의 적당한 공급원일 수 있다. 파라믹소바이러스 과는 파라인플루엔자 바이러스 타입 1, 파라인플루엔자 바이러스 타입 3, 소 파라인플루엔자 바이러스 타입 3, 루불라바이러스(멈프스 바이러스), 파라인플루엔자 바이러스 타입 2, 파라인플루엔자 바이러스 타입 4, 뉴캐슬병 바이러스(닭), 우역, 홍역 및 개디스템퍼를 포함하는 모르비리바이러스, 호흡기 세포융합 바이러스를 포함하는 뉴모바이러스를 포함한다. 인플루엔자 바이러스는 오소믹소바이러스 과 내로 분류되며 적당한 항원(예를 들어, HA 단백질, N1 단백질)의 공급원이다. 분야바이러스 과는 분야바이러스 속(캘리포니아뇌염, La Crosse), 플레보바이러스(리프트 밸리열), 한타바이러스 (퓨어말라(puremala)는 헤마하긴(hemahagin) 열 바이러스이다), 나이로바이러스(진드기증(Nairobi sheep disease)) 및 다양한 미지정 분야바이러스를 포함한다. 아레나바이러스 과는 LCM 및 라사열 바이러스에 대한 항원의 공급원을 제공한다. 레오 바이러스 과는 레오바이러스, 로타바이러스(어린이에게서 급성위장염을 야기한다), 오르비바이러스, 및 컬티바이러스(콜로라도진드기열, 레봄보(Lebombo) (인간), 말 뇌증, 청설병) 속을 포함한다.
레트로바이러스 과는 고양이 백혈병 바이러스, HTLVI 및 HTLVII, 렌티바이러스(인간 면역결핍 바이러스(HIV), 유인원 면역결핍 바이러스(SIV), 고양이 면역부전 바이러스(FIV), 말 전염성 빈혈 바이러스 및 스푸마바이러스를 포함)로서 인간 및 수의과 질병을 포함하는 옹코리비리날(oncorivirinal) 아과를 포함한다. 렌티바이러스 중에서, 많은 적당한 항원이 기술되었고 용이하게 선택될 수 있다. 적당한 HIV 및 SIV 항원의 예는, 제한 없이, gag, pol, Vif, Vpx, VPR, Env, Tat, Nef, 및 Rev 단백질뿐만 아니라 그것의 다양한 단편을 포함한다. 예를 들어, Env 단백질의 적당한 단편은 gp120, gp160, gp41과 같은 어떤 그것의 서브유닛, 또는 그것의 더 작은 단편, 예를 들어, 길이에 있어 적어도 약 8개의 아미노산을 포함할 수 있다. 유사하게, tat 단백질의 단편이 선택될 수 있다. [미국 특허 5,891,994호 및 미국 특허 6,193,981호 참조] 또한, D.H. Barouch et al, J. Virol., 75(5):2462-2467 (2001년 3월), 및 R.R. Amara, et al, Science, 292:69-74 (2001년 4월 6일)에서 기술되는 HIV 및 SIV 단백질 참조. 다른 예에서, HIV 및/또는 SIV 면역성 단백질 또는 펩티드는 융합 단백질 또는 다른 면역성 분자를 형성하기 위해 사용될 수 있다. 예를 들어, 2001년 8월 2일 공개된 WO 01/54719, 및 1999년 4월 8일 공개된 WO 99/16884에서 기술되는 HIV-1 Tat 및/또는 Nef 융합 단백질 및 면역 요법을 참조. 본 발명은 HIV 및/또는 SIV 면역원성 단백질 또는 본원에 설명되는 펩디드로 제한되지 않는다. 게다가, 이들 단백질에서 다양한 변형이 기술되었고, 또는 당업자에 의해 용이하게 만들어질 수 있었다. 예를 들어, 미국 특허 5,972,596에서 기술되는 변형된 구역 단백질(gag protein)을 참조. 추가로, 어떤 요망되는 HIV 및/또는 SIV 면역원은 단독으로 또는 조합하여 전달될 수 있다. 이러한 조합은 단일 벡터 또는 다중 벡터로부터 발현을 포함할 수 있다. 선택적으로, 다른 조합은 단백질 형태에서 하나 이상의 면역원의 전달과 함께 하나 이상의 발현된 면역원의 전달을 수반할 수 있다. 이러한 조합은 하기에서 더욱 상세하게 논의된다.
파포바바이러스 과는 폴리오마바이러스 아과(BKU 및 JCU 바이러스) 및 파필로마바이러스 아과(암 또는 유두종의 악성 진행과 관련)를 포함한다. 아데노바이러스 과는 호흡기 질병 및/또는 장염을 야기하는 바이러스(EX, AD7, ARD, O. B.)를 포함한다. 파보바이러스 과 고양이 파보 바이러스(고양이 장염), 고양이 범백혈구감소증 바이러스, 개 파보바이러스 및 돼지 파보바이러스. 헤르페스바이러스 과는 심플렉스바이러스 속 (HSVI, HSVII), 바리셀로바이러스 (가성광견병, 바리셀라-조스터 바이러스)를 포함하는 알파헤르페스바이러스 아과 및 시토메갈로 바이러스(HCMV, 무로메갈로바이러스)를 포함하는 베타헤르페스바이러스 아과 및 림포크립토바이러스 속, EBV (버킷 임파종(Burkitts lymphoma)), 전염성비기관염, 마렉병 바이러스, 및 라디노바이러스를 포함하는 감마헤르페스바이러스 아과를 포함한다. 수두 바이러스과는 오르토폭스바이러스(바리올라 (두창) 및 백시니아 (우두)), 파라폭스바이러스, 아비폭스바이러스, 카프리폭스바이러스, 레포리폭스바이러스, 수이폭스바이러스 속을 포함하는 초르도폭스바이러스아과, 및 엔토모폭스바이러스 아과를 포함한다. 헤파드나바이러스 과는 B형 간염 바이러스를 포함한다. 적당한 항원의 공급원일 수 있는 한 미분류 바이러스는 델타감염 바이러스이다. 또 다른 바이러스 공급원은 조류 전염성 훼브리셔스낭병 바이러스 및 돼지 호흡기 생식기 증후군 바이러스를 포함할 수 있다. 알파바이러스 과는 말동맥염바이러스 및 다양한 뇌염바이러스를 포함한다.
다른 병원체에 대한 인간 또는 비-인간 동물을 면역화하는데 유용한 면역원은, 예를 들어, 인간 및 비-인간 척추동물을 감염시키는 박테리아, 진균, 기생충미생물 또는 다세포 기생충, 또는 암 세포 또는 종양 세포를 포함한다. 박테리아 병원체의 예는 폐렴쌍구균; 포도상구균; 및 연쇄상구균을 포함하는 병원체의 그램양성 구균을 포함한다. 병원체의 그램-음성 구균은 뇌척수막염균; 임균을 포함한다. 병원체의 장 그램-음성 간균은 장내세균(enterobacteriaceae); 슈도모나스, 아시네토박테리아 및 에이케넬라; 멜리오이도시스; 살모넬라; 시겔라; 헤모필루스; 모락셀라; H. 듀크레이(무른 궤양을 야기함); 브루셀라균; 프란시셀라 툴라렌시스균(툴라레미아를 야기); 예르시니아(파스튜렐라); 모닐리포르미스사슬막대균 및 나선균을 포함하고; 그램-양성 간균은 리스테리아모노사이토제네스; 돈단독균(erysipelothrix rhusiopathiae); 코리네박테리움 디프테리아(디프테리아); 콜레라; 탄저균 (탄저병); 도노반증(서혜육아종); 및 바르토넬라증을 포함한다. 병원성 혐기성 세균에 의해 야기되는 질병은 파상풍; 보툴리즘; 다른 클로스트리디아; 결핵; 나병; 및 다른 마이코박테리아를 포함한다. 병원성 스피로헤타병은 매독; 트레포네마병: 매종, 핀타 및 풍토병성 매독; 및 렙토스피라병을 포함한다. 더 고등의 병원체 박테리아 및 병원성 진균에 의해 야기되는 다른 감염은 방선균증; 노카르디아증; 효모균증, 분아진균증, 히스토플라스마증 및 콕시디오이데스 진균증; 칸디다증, 아스페르길루스증, 및 뮤코르 진균증; 스포로트릭스증; 파라콕시디오이드마이세스증, 페트리엘리듐증, 토룰롭시스증, 균종 및 색소진균증; 및 피부사상균증을 포함한다. 리케차감염은 발진티푸스, 로키산 홍반열, Q열, 및 리켓치아폭스를 포함한다. 마이코플라스마 및 클라미디아 감염의 예는: 마이코플라즈마 뉴모니아; 서혜 림프 육아종; 앵무새병; 및 주산기 클라미디아 감염을 포함한다. 병원성 진핵생물은 병원성 원생동물 및 장내 기생충을 포함하고, 이에 의해 생성되는 감염은: 아메바성 감염; 말라리아; 리슈만편모충증; 트리파노소마증; 톡소플라스마증; 폐포자충(Pneumocystis carinii); 트리칸스(Trichans); 톡소포자충(Toxoplasma gondii) ; 바베스열원충증; 지알디아증; 선모충병; 필라리아병; 주혈흡충병; 선충; 흡충 또는 요행; 및 촌충류(촌충) 감염을 포함한다.
다수의 이들 유기체 및/또는 이에 의해 생성되는 독소는 생물학적 공격에서 사용을 위한 가능성을 가지는 약제로서 질병 대책 센터(Centers for Disease Control)[(CDC), Department of Heath and Human Services, USA]에 의해 확인되었다. 예를 들어, 일부의 이들 생물학적 약제는 탄저균 (탄저병), 클로스트리디움 보툴리늄 및 그것의 독소(보툴리즘), 페스트균(Yersinia pestis)(흑사병), 대두창(두창), 프란키셀라 툴라렌시스(Francisella tularensis)(툴라레미아), 및 바이러스성 출혈열[필로바이러스(예를 들어, Ebola, Marburg], 및 아레나바이러스[예를 들어, Lassa, Machupo])를 포함하며, 이들 모두는 현재 카테고리 A 약제로서 분류되며; 콕시엘라 부르네티(Q 열); 브루셀라 종(브루셀라병), 비저균(Burkholderia mallei)(마비저), 부르코홀데리아 슈도 말레이(Burkholderia pseudomallei)(유비저), 피마자 및 그것의 독소(리신 독소), 클로스트리듐 균(clostridium perfringen) 및 그것의 독소(엡실론 독소), 포도상구균 종 및 그것의 독소(엔테로톡시 B), 클라미디아 시타시(앵무새병), 물의 안전성 위협(예를 들어, 비브리오콜레라, 크립토스포리듐 파르붐), 발진티푸스(리케챠 포와제키(Rickettsia powazekii)), 및 바이러스성뇌염(알파바이러스, 예를 들어, 베네수엘라마뇌염; 동부형마 뇌막염; 서부형 마뇌염)를 포함하고; 이들 모두는 카테고리 B 약제로서 분류되고; 니판 바이러스 및 한타바이러스를 포함하고, 이것은 카테고리 C 약제로서 분류된다. 게다가, 이렇게 분류 또는 다르게 분류되는 다른 유기체는 장래의 목적을 위해 확인 및/또는 사용될 수 있다. 본원에서 기술되는 바이러스 벡터 및 다른 구조체는 이들 유기체, 바이러스, 그것의 독소 또는 다른 부산물로부터, 이들 생물학적 약제에 의한 감염 또는 다른 역반응을 예방 및/또는 치료할 항원을 전달하는데 유용하다는 것이 이해될 것이다.
T 세포의 가변 영역에 대해 면역원을 전달하는 SAdV-40, SAdV-31 또는 SAdV-34 벡터의 투여는 이들 T 세포를 제거하기 위해 CTL을 포함하는 면역반응을 일으키는 것으로 예상된다. RA에서, 질병에 수반되는 TCR의 몇몇의 특정 가변 영역은 특성이 기술되었다. 이들 TCR은 V-3, V-14, V-17 및 Vα-17을 포함한다. 따라서, 적어도 하나의 이들 폴리펩티드를 암호화하는 핵산 서열의 전달은 RA에 수반된 T 세포를 표적화할 면역반응을 유발할 것이다. MS에서, 질병에 수반된 TCR의 몇몇 특정 가변 영역은 특성이 기술되었다. 이들 TCR은 V-7 및 Vα-10을 포함한다. 따라서, 적어도 하나의 이들 폴리펩티드를 암호화하는 핵산 서열의 전달은 MS에 수반되는 T세포를 표적화할 면역반응을 유발할 것이다. 경피증에서, 질병에 수반된 TCR의 몇몇 특정 가변 영역은 특성이 기술되었다. 이들 TCR은 V-6, V-8, V-14 및 Vα-16, Vα-3C, Vα-7, Vα-14, Vα-15, Vα-16, Vα-28 및 Vα-12을 포함한다. 따라서, 적어도 하나의 이들 폴리펩티드를 암호화하는 재조합 유인원 아데노바이러스의 전달은 경피증에 수반된 T 세포를 표적화할 면역 반응을 일으킬 것이다.
C.
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-매개 전달 방법
선택된 유전자의 치료 수준, 또는 면역의 수준은, 만약에 있다면, 부스터에 대한 필요를 결정하기 위해 모니터링될 수 있다. 혈청에서 CD8+ T 세포 반응, 또는 선택적으로 항체 타이터의 평가에 따라서, 선택적인 부스터 면역화가 요망될 수 있다. 선택적으로, 재조합 SAdV-40, SAdV-31 또는 SAdV-34 벡터는 단일 투여에서 또는 예를 들어, 다른 활성 성분을 수반하는 요법 또는 치료의 과정과 조합하는 다양한 요법 또는 프라임-부스트 요법에서 전달될 수 있다. 다양한 이러한 요법은 당업계에서 기술되었고 용이하게 선택될 수 있다.
예를 들어, 프라임-부스트 요법은 일차 면역 체계로 DNA(예를 들어, 플라스미드) 기초 벡터를, 이차의 부스터로 이러한 항원을 암호화하는 서열을 전달하는 단백질 또는 재조합 바이러스와 같은 일반적인 항원의 투여를 수반할 수 있다. 예를 들어, 참고로써 포함되는 2000년 3월 2일 공개된 WO 00/11140 참조. 또 다르게는, 면역 요법은 항원, 또는 단백질을 전달하는 벡터(바이러스 또는 DNA-기초)에 대한 면역 반응을 촉진하기 위해 재조합 SAdV-40, SAdV-31 또는 SAdV-34 벡터의 투여를 수반할 수 있다. 또 다른 대안으로, 면역 요법은 단백질의 투여 후 항원을 암호화하는 벡터와 함께 부스터를 수반한다.
한 구체예에서, 상기 항원을 전달하는 플라스미드 DNA 벡터를 전달한 후 재조합 SAdV-40, SAdV-31 또는 SAdV-34 벡터로 부스팅함으로써 선택된 항원에서 면역반응을 프라이밍하고 부스팅하는 방법이 기술된다. 한 구체예에서, 프라임-부스트 요법은 프라임 및/또는 부스트 비히클로부터 멀티단백질의 발현을 수반한다. 예를 들어, HIV 및 SIV에 대한 면역 반응을 발생시키는데 유용한 단백질 서브유닛의 발현에 대한 멀티단백질 요법을 기술하는 R. R. Amara, Science, 292:69-74 (2001년 4월 6일) 참조. 예를 들어, DNA 프라임은 단일 전사로부터 Gag, Pol, Vif, VPX 및 Vpr 및 Env, Tat, 및 Rev를 전달할 수 있다. 또 다르게는, SIV Gag, Pol 및 HIV-1 Env는 재조합 SAdV-40, SAdV-31 또는 SAdV-34 아데노바이러스 구조체에서 전달된다. 또 다른 요법은 WO 99/16884 및 WO 01/54719에서 기술된다.
그러나, 프라임-부스트 요법은 HIV에 대한 면역 또는 이들 항원의 전달에 제한되지 않는다. 예를 들어, 프라이밍은 제 1 SAdV-40, SAdV-31 또는 SAdV-34 벡터에 의한 전달단계 후 제 2 Ad 벡터로, 또는 단백질 형태에서 항원 그 자체를 함유하는 조성물과 함께 부스팅하는 단계를 수반할 수 있다. 한 예에서, 프라임-부스트 요법은 항원이 유래된 바이러스, 박테리아 또는 다른 유기체에 대한 보호 면역 반응을 제공할 수 있다. 다른 구체예에서, 프라임-부스트 요법은 치료제가 투여되는 질환의 존재의 검출을 위한 통상적인 분석을 사용하여 측정될 수 있는 치료효과를 제공한다.
프라이밍 조성물은 요망되는 면역 반응이 표적화되는 항원에 따라서 용량 의존적 방법으로 다양한 자리에 투여될 수 있다. 주사(들)의 양 또는 위치 또는 약학적 담체는 제한되지 않는다. 오히려, 요법은 이들 각각이 매 시간마다, 매일, 주마다 또는 매월 또는 매년마다 투여되는 단일 용량 또는 투약량을 포함할 수 있는 프라이밍 및/또는 부스팅 단계를 수반할 수 있다. 예로서, 포유동물은 담체에서 약 10 μg 내지 약 50 μg의 플라스미드를 함유하는 하나 이상의 용량을 수용할 수 있다. DNA 조성물의 바람직한 양은 약 1 μg 내지 약 10,000 μg의 DNA 벡터의 범위에 있다. 투약량은 피험자 체중 당 1 μg 내지 1000 μg DNA로 다양할 것이다. 전달의 양 또는 자리는 포유동물의 동일성 및 질환에 기초하여 바람직하게 선택된다.
포유동물에 대한 항원의 전달에 적당한 벡터의 투약 단위는 본원에서 기술된다. 벡터는 등장 식염수; 등장 염 용액 또는 이러한 투여에서 당업자에게 명백할 다른 제형과 같은 약학적으로 또는 생리학적으로 허용가능한 담체로 현탁 또는 용해됨으로써 투여를 위해 제조된다. 적절한 담체는 당업자에게 명백할 것이고 투여 경로의 상당 부분에 의존할 것이다. 본원에 설명되는 조성물은 상기 기술된 경로에 따라서, 서방성 제형으로 생체분해가능한 생체적합성 폴리머를 사용하여, 또는 미셀, 겔 및 리포좀을 사용하는 현장 전달에 의해 포유동물에 투여될 수 있다. 선택적으로, 프라이밍 단계는 또한 본원에 설명되는 바와 같은 프라이밍 조성물, 적당한 양의 보조제와 함께 투여하는 단계를 포함한다.
바람직하게는, 부스팅 조성물은 포유동물 피험자에 대해 프라이밍 조성물을 투여 후 약 2 내지 약 27주에 투여된다. 부스팅 조성물의 투여는 프라이밍 DNA 백신에 의해 투여되는 동일한 항원을 함유하는 또는 전달할 수 있는 부스팅 조성물의 유효량을 사용하여 수행된다. 부스팅 조성물은 동일한 바이러스 공급원(예를 들어, 본 발명의 아데노바이러스 서열) 또는 다른 공급원으로부터 유래된 재조합 바이러스 벡터로 구성될 수 있다. 또 다르게는, "부스팅 조성물"은 프라이밍 DNA 백신에서, 그러나 조성물이 숙주에서 면역 반응을 유발하는 단백질 또는 펩티드의 형태로 암호화되는 바와 같은 동일한 항원을 함유하는 조성물일 수 있다. 다른 구체예에서, 부스팅 조성물은 포유동물 세포에서 그것의 발현을 지시하는 조절 서열, 예를 들어, 잘-공지된 박테리아 또는 바이러스 벡터와 같은 벡터의 제어하에서 항원을 암호화하는 DNA 서열을 함유한다. 부스팅 조성물의 일차적 요건은 조성물의 항원이 프라이밍 조성물에 의해 암호화되는 동일 항원, 또는 교차-반응 항원이다.
다른 구체예에서, SAdV-40, SAdV-31 또는 SAdV-34 벡터는 또한 다양한 다른 면역 및 치료 요법에서 사용을 위해 적합하게 된다. 이러한 요법은 다른 항원형 캡시드의 Ad 벡터와 함께 동시에 또는 순차적으로 SAdV-40, SAdV-31 또는 SAdV-34 벡터의 전달, SAdV-40, SAdV-31 또는 SAdV-34 벡터가 동시에 또는 순차적으로 비-Ad 벡터와 함께 전달되는 요법, SAdV-40, SAdV-31 또는 SAdV-34 벡터가 동시에 또는 순차적으로 단백질, 펩티드 및/또는 다른 생물학적으로 유용한 치료 또는 면역원성 화합물과 함께 전달되는 요법을 수반할 수 있다. 이러한 사용은 당업자에게 용이하게 명백할 것이다.
하기 예는 SAdV-40, SAdV-31 또는 SAdV-34의 클로닝 및 대표적인 재조합 SAdV-40, SAdV-31 또는 SAdV-34 벡터의 구성을 예시한다. 이들 예는 단지 예시적인 것이며, 본 발명의 범주를 제한하는 것은 아니다.
실시예
1 - 유인원
아데노바이러스의
분리 및
PCR
분석
University of Louisiana New Iberia Research Center, 4401 W. Admiral Doyle Drive, New Iberia, Louisiana, USA에서 침팬지 집단, 및 Michael E. Keeling Center for Comparative Medicine and Research, University of Texas M. D. Anderson Cancer Center, Bastrop, Texas, USA에서 침팬지 집단으로부터 채변 샘플을 얻었다. 행크스 평형화 염 용액의 현탁액에서 침팬지 채변 샘플로부터의 상청액을 0.2 미크론 실린지 필터를 통해 멸균 여과하였다. 100 μl의 각각의 여과된 샘플을 인간 셀 라인 A549 배양물에 접종하였다. 이들 세포를 10% FBS, 1% Penn-Strep 및 50μg/ml 겐타마이신과 함께 Ham's F12에서 성장시켰다. 배양물에서 약 1 내지 2주 후, 시각적 세포변성 효과(CPE)는 몇몇의 접종물과 함께 세포 배양물에서 명백하였다. 아데노바이러스를 아데노바이러스 정제를 위한 표준 공개된 염화세슘 기울기 기술을 사용하여 A549 세포에서 배양물로부터 정제하였다. 정제한 아데노바이러스로부터 DNA를 분리하였고 Qiagen Genomic services, Hilden, Germany에 의해 완전히 서열화하였다.
바이러스 DNA 서열의 계통발생적 분석에 기초하여, 아데노바이러스 지정된 유인원 아데노바이러스 31 (SAdV-31), 유인원 아데노바이러스 34 (SAdV-34), 유인원 아데노바이러스 40 (SAdV-40)을 인간 아군 C로서 동일 아군 내가 되도록 결정하였다.
벡터를 만들기 위해 사용되는 방법은 전체 E1-결핍 아데노바이러스 벡터의 박테리아 플라스미드 분자 클론을 우선 만든 다음 E1 보완 셀 라인 HEK 293에 플라스미드 DNA의 트랜스펙션을 하여 바이러스 벡터를 구제한다.
E1-결핍 아데노바이러스 벡터의 분자 클론을 만들기 위해, 희소-절단 제한 효소 I-CeuI 및 PI-SceI에 대한 인식 자리가 E1 결핍 대신에 삽입된 곳에서 E1-결핍 아데노바이러스의 플라스미드 분자 클론을 우선 만들었다. I-CeuI 및 PI-SceI 옆에 위치하고, 이들 제한 효소를 사용하여 절단한 발현 카세트를 E1-결핍 아데노바이러스 플라스미드 클론에 연결하였다. E1 결핍 대신에 요망되는 발현 카세트를 포함하는 플라스미드 아데노바이러스 분자 클론을 HEK 293 세포에 트랜스펙팅하여 재조합 아데노바이러스 벡터를 구제하였다. 트랜스펙션 다음의 구제는 제한 효소 분해에 의해 플라스미드로부터 선형의 아데노바이러스 게놈을 우선 방출함으로써 가능하게 된다는 것을 발견하였다.
실시예
2- 통상적인 분자 생물학 기술을 사용하는
SAdV
-40,
SAdV
-31 및 SAdV-34의 벡터 구성
A. SAdV-40 (아군 C)을 사용하는 E1 결핍 벡터를 기술한 바와 같이 제조하였다.
1.
pSR2
의 구성:
PmeI 자리 옆에 위치하는 SnaBI, FseI, MluI, PacI 및, EcoRV 자리를 함유하는 링커를 하기와 같이 EcoRI 및 NdeI에 의해 pBR322 절단으로 클로닝하였다.
2.
pSR7
의 구성:
이는 PmeI 자리 옆에 위치하는 SnaBI, FseI, NdeI, NheI, EcoRI, PacI 및 EcoRV 자리를 함유하는 링커를 만든다. pSR7에서, 이 링커는 EcoRI에서 NdeI 자리로 pBR322 단편을 대체한다.
3.
PCR
에 의한
E1
결핍 왼쪽 말단의 구성
New England Biolabs (NEB) Phusion 키트를- 키트에서 공급하는 각각 프라이머, 0.5 μM, dNTP - 각각 0.2mM, 효소 - NEB Phusion, 완충제- 사용하였다.
PCR 조건(모두 3개 반응에 대해) - 98°-30초, [98°-10초, 어닐링 - 30초, 72°- 15초]의 25 주기
PCR
1
올리고머
PCR
2
올리고머
SOE 3의 5' 19개 염기는 SOE 2에 상보적이다.
SOE 4의 5' 10개 염기는 NdeI 자리를 포함한다(pSR7에 제 1 생성물을 클로닝하기 위함).
PCR
3
PCR 1 및 PCR 2의 생성물을 합하기 위해, 20μl의 각 PCR을 1% Seaplaque gel에서 실행하였다. 밴드를 절단하였고 아가로오스를 68°에서 용융시켰다. 5μl의 각각의 용융된 겔을 190μl의 물과 합하였다. 4μl의 희석한 혼합물을 프라이머 SOE 1 및 SOE 4를 사용하여 200μl PCR 반응에서 주형으로서 사용하였고, 61°에서 어닐링하였다. 예상한 생성물 크기는 747 bp였다.
4.
pSR7
C14
LEdelE1
IP
를 수득하기 위한 I-
CeuI
및
PI
-
SceI
자리의 삽입과 함께 기능적
E1
결실을 포함하는
SAdV
-40 왼쪽 말단의
클로닝
최종 PCR 생성물을 NdeI로 분해하였고 SnaBI 및 NdeI로 pSR7 cut에 연결하였다. 미니프렙을 PmeI(expect 2073, 809)로 분해함으로써 분석하였다. 4개를 프라이머 pBRfwd [CACCTGACGTCTAAGAAACC (SEQ ID NO: 103)] 및 pBRrev [TG AGCG AGGAAGCGGAAG (SEQ ID NO: 104)]로 서열화하였다. 서열은 클로닝된 바이러스 왼쪽 말단 서열의 처음 79 bp 다음에 44bp 결실이 존재한다는 것을 나타내었다. 결실을 고치기 위해, SacII - NdeI을 다른 플라스미드로부터 교환하였다(NdeI까지 SAdV-40 바이러스 DNA 3433 bp 왼쪽 말단을 포함, 결실을 고치기 위해 pSR7에서 클로닝된 자리).
5.
EcoRI
자리(33952)로부터
SAdV
-40 바이러스 오른쪽 말단의
클로닝
.
SAdV-40 바이러스 DNA를 EcoRI로 분해하였고, 3767 bp 오른쪽 말단 단편을 EcoRI 및 EcoRV 사이의 pSR7 C14 LE delE1 IP로 클로닝하여 pC40IP LE RE를 수득하였다.
6.
SAdV
-40 바이러스
NdeI
-
EcoRI
(3433 - 33952) 단편의
클로닝
플라스미드 pC40IP LE RE를 NdeI 및 EcoRI로 분해하였고, 33952 bp 바이러스 NdeI - EcoRI 단편을 연결하였다. 클론을 pC40 IP로 불렀다.
B.
SAdV
-31의 벡터 구성
SAdV-31 (아군 C)을 사용하는 E1 결실 벡터를 설명한 바와 같이 제조하였다.
1.
pSR2
의 구성:
PmeI 자리 옆에 위치하는 SnaBI, FseI, MluI, PacI 및, EcoRV 자리를 함유하는 링커를 하기와 같이 EcoRI 및 NdeI에 의한 pBR322으로 클로닝하였다.
올리고머
2.
pSR7
의 구성:
플라스미드 pSR2를 MluI로 분해하였고, 어닐링한 올리고머
3.
PacI
자리 (37008)로부터
SAdV
-31 바이러스 오른쪽 말단의
클로닝
.
SAdV-31 바이러스 DNA를 PacI로 분해하였고, 821 bp 오른쪽 말단 단편을 PacI 및 EcoRV 사이의 pSR7에 클로닝하여 pSR7 C31 RE를 수득하였다.
4.
NheI
(9449)에 바이러스 왼쪽 말단의
클로닝
SAdV-31 바이러스 DNA를 NheI로 분해하였고 9449 bp 왼쪽 말단 단편을 SnaBI 및 NheI 사이의 pSR7 C31 RE에 클로닝하여 pSR7 C31 LERE를 수득하였다.
5.
pC31
LERE1
IPf
를 수득하기 위한 I-
CeuI
및
PI
-
SceI
자리의 삽입에 의한 기능적
E1
결실
플라스미드 pSR7 C31LERE를 BlpI와 NdeI (두 자리 모두에서 Klenow를 채움)사이에서 결실하여 E1a 및 대부분의 E1b 코딩 영역을 결실하였고; 그 자리에서 DNA 단편(pBleuSK I-PI로부터의 EcoRV 단편은 I-CeuI 및 PI-SceI에 대한 자리를 포함한다)을 연결하여 pC31 LERE IP를 수득하였다.
6.
SAdV
-31 바이러스
NheI
-
PacRI
(9449 - 37008) 단편의
클로닝
플라스미드 pC31 LERE IP를 NheI 및 PacI로 분해하였고, 27559 bp 바이러스 NdeI - EcoRI 단편을 연결하였다. 클론을 pC31 IP로 불렀다.
C.
Ad
E1
결실을 가능하게 하는
클로닝
자리의 삽입
E1 결실 대신에 I-CeuI 및 PI-SceI 인식 자리를 포함하는 DNA 절편을 삽입하기 위해, 플라스미드 pBleuSK I-PI를 사용하였다. 플라스미드 pBleuSK I-PI는 pBluescript II SK(+) (Stratagene)의 EcoRV 자리에 삽입된 654 bp 단편을 함유한다. 654 bp 절편은 희소-절단 제한 효소 I-CeuI 및 PI-SceI를 위한 인식 자리를 포함한다. E1 결실 대신에 I-CeuI 및 PI-SceI 인식 자리를 포함하는 DNA 절편을 삽입하기 위해서, pBleuSK I-PI를 EcoRV로 분해하였고, 654 bp 단편을 아데노바이러스 게놈 E1 결실의 위치에 연결하였다.
삽입한 DNA의 서열은 하기에서 EcoRV 인식 자리 옆에 위치함을 나타낸다. I-CeuI 및 PI-SceI에 대한 인식 서열을 밑줄친다.
인플루엔자 바이러스 뉴클레오단백질을 발현시키는 E1-결실 아데노바이러스 벡터를 구성하기 위해서, H1N1 인플루엔자 A 바이러스 NP를 암호화하는 뉴클레오티드 서열(A/Puerto Rico/8/34/Mount Sinai, GenBank 등록번호 AF389119.1)은 최적화된 코돈이었고, 완전히 합성하였다(Celtek Genes, Nashville, TN). 인간 사이토메갈로바이러스 초기 프로모터, 합성 인트론(플라스미드 pCI (Promega, Madison, Wisconsin)로부터 얻음), 코돈 최적화 인플루엔자 A NP 코딩 서열 및 소 성장 호르몬 폴리아데닐화 신호로 구성되는 발현을 구성하였다. 플라스미드 pShuttle CMV PI FIuA NP는 상기 기술된 발현 카세트를 포함하며, 이는 각각 희소-절단 제한 효소 I-CeuI 및 PI-SceI (New England Biolabs)에 대한 인식 자리 옆에 위치한다. E1-결핍 아데노바이러스 벡터의 분자 클론을 만들기 위해서, E1-결핍 아데노바이러스의 플라스미드 분자 클론을 본 실시예의 앞 부분에서 기술한 바와 같이 만들었고, 희소-절단 제한 효소 I-CeuI 및 PI-SceI에 대한 인식 자리를 E1 결실 대신 삽입하였다. E1-결실 아데노바이러스 플라스미드를 그 후 I-CeuI 및 PI-SceI로 분해하였고 발현 카세트(동일 효소에 의해 분해)를 연결하였다. 결과 아데노바이러스 플라스미드 분자 클론을 HEK 293 세포에 트랜스펙팅하여 재조합 아데노바이러스 벡터를 구제하였다. 트랜스펙션 후 구조는 제한 효소 분해에 의해 플라스미드로부터 선형 아데노바이러스 게놈을 우선 방출함으로써 가능하게 됨을 발견하였다.
실시예
3 - 교차-중화 항체의 평가
야생형 SAdV-40, SAdV-31, SAdV-34를 직접 면역 형광법에 의해 모니터링되는 감염 억제 중화 항체 분석을 사용하여 인간 아데노바이러스 5(아종 C) 및 침팬지 아데노바이러스 7(SAdV-24), 및 인간 풀링된 IgG와 비교하여 교차-중화 활성에 대해 평가하였다. 일반적 인간 집단이 노출되는 다수의 항원에 대한 항체를 함유하기 때문에, 인간 풀링된 IgG[Hu Pooled IgG]를 상업적으로 구입하고, 면역타협 환자에서 투여를 위해 승인한다. 인간 풀링된 IgG에 대한 유인원 아데노바이러스에서 중화 항체의 존재 또는 부존재는 일반적 모집단에서 이들 아데노바이러스에 대한 항체의 보급의 반영이다.
분석을 하기와 같이 수행하였다. HAdV-5 또는 SAdV-24로 주사한 토끼로부터의 혈청 샘플을 35분 동안 56℃에서 가열하여 불활성화하였다. 야생형 아데노바이러스(108 입자/웰)를 무혈청 둘베코 변형 이글 배지(DMEM)에서 희석하였고, 37℃에서 1시간 동안 DMEM에서 가열-불활성화된 혈청의 2-배 연속 희석으로 배양하였다. 이후에, 혈청-아데노바이러스 혼합물을 105 단일층 A549 세포와 함께 웰 내의 슬라이드에 첨가하였다. 1시간 후, 각 웰의 세포를 100 μl의 20% 소 태아혈청(FBS)-DMEM으로 보충하였고, 5% CO2로 37℃에서 22시간 동안 배양하였다. 다음에, 세포를 PBS로 2회 헹구고 DAPI로 염색하였고, 염소에 FITC로 표지된, 광범위하게 교차 반응성인 항체(Virostat)를 파라포름알데히드(4%, 30 분)에서 고정 및 0.2% Triton (4℃, 20 분)에서 침투 후 HAdV-5에 대해 길렀다. 감염의 수준을 현미경관찰 하에서 FITC 양성 세포의 수를 카운팅함으로써 결정하였다. NAB 타이터를 나이브(naive) 혈청 대조군과 비교하여 50% 이상으로써 아데노바이러스 감염을 억제한 가장 높은 혈청 희석으로서 기록한다.
< 1/20의 타이터 값이 나타나면, 중화 항체 농도는 검출의 제한, 즉 1/20 이하이다.
이들 데이터는 일반 모집단에서 SAdV-31 및 SAdV-40에 대해 최소한의 면역반응성이 있음을 나타낸다. 이들 데이터는 HAdV-5 및 SAdV-24와 교차-반응하지 않는 앞의 표에 있는 유인원 아데노바이러스가 아데노바이러스의 순차적 전달을 수반하는 요법, 예를 들어, 프라임-부스트 또는 암 치료법에 유용할 수 있음을 추가로 나타낸다.
실시예
4 - 사이토카인 유도
형질세포양 수지상세포를 인간 말초혈액 단핵구(PBMCs)로부터 분리하였고, 96웰 플레이트로 배지에서 배양하였고 아데노바이러스로 감염시켰다. 48시간 후 세포를 스핀다운하고 상청액을 수집하였고 인터페론 α의 존재하에서 분석하였다.
더 구체적으로, PBMC를 펜실베니아 유니버시티에서 CFAR(Center For AIDS Research) 면역학 코어로부터 획득하였다. 3억 개의 이들 세포를 그 후 키트와 함께 제공된 설명서에 따라서 Miltenyi Biotec제의 "인간 형질세포양 수지상세포 분리 키트"를 사용하여 형질세포양 수지상세포(pDCs)를 분리하기 위해 사용하였다. 이 키트를 사용하는 분리는 모든 다른 세포 종류를 제거하는 것을, 그러나 pDC는 PBMC로부터 제거하는 것을 기초로 하였다.
최종 세포 수는 보통 도너로부터 도너까지 다양하지만, 4십만 내지 7십만 개의 세포의 범위에 있다. 따라서 발생된 데이터(하기 논의)는 다중 도너로부터의 세포의 분석에서 비롯된다. 그렇지만 놀랍게도, 인터페론 또는 다른 사이토카인 방출에 기초한 아군의 분리는 다양한 도너로부터 세포를 분리할 때조차 유지된다.
세포를 L-글루타민, 10% 소 태아 혈청(Mediatech), 1OmM 헤페스 완충제 용액(Invitrogen), 항생물질(페니실린, 스트렙토마이신 및 겐타마이신-Mediatech 제) 및 인간-인터류킨 3 (20ng/mL - R&D)으로 보충한 RPMI-1640 배지(Mediatech)에서 배양하였다. 야생형 아데노바이러스를 10,000 (세포 당 10,000개의 바이러스 입자, 106 세포/ml의 농도로)의 감염다중도(MOI)에서 세포에 직접 첨가하였다. 48 시간 후, 세포를 스핀 다운하였고, 상청액을 인터페론의 존재하에서 분석하였다. 사이토카인을 제조업자로부터 추천된 프로토콜을 사용하여 PBL 생물의학 연구소로부터 효소-결합면역흡착분석법(ELISA) 키트를 사용하여 분석하였다.
본 연구는 아군 C 아데노바이러스가 IFNα의 검출가능하지 않은 양을 만든다는 것을 나타내었다(본 분석은 1250 pg/mL의 검출 제한을 가진다). 반대로, 아군 E 아데노바이러스의 모든 시험 멤버는 IFNα를 생성하였고, 일반적으로 아군 B 아데노바이러스와 비교하여 상당히 우수한 IFNα를 생성하였다.
다양한 다른 사이토카인을 또한 아데노바이러스의 스크리닝에서 검출하였다. 그러나, 일반적으로, 아군 E 아데노바이러스는 아군 C 아데노바이러스보다 상당히 더 높은 수준의 IL-6, RANTES, MIP-1α, TNF-α, IL-8, 및 IP-10을 생성하였다. 아군 B 아데노바이러스는 또한 IFNα, IL-6, RANTES, 및 MIP1α의 유도에서 아군 C 아데노바이러스를 능가하였다.
상당한 세포 용혈이 이 연구에서 관찰되지 않았기 때문에, 이는 감염과 상관없이, 바이러스 복제의 어떤 상당한 양의 존재하에서 사이토카인이 아군 E 아데노바이러스와 세포를 접촉함으로써 생성된다는 것을 제안한다.
다른 연구에서(제시하지 않음), 세포를 중공 C7 캡시드 단백질(Ad 아군 E) 또는 UV-불활성 아데노바이러스 C7 바이러스 벡터(UV 불활성화는 교차-연결을 야기하며, 아데노바이러스 유전자 발현을 제거한다) 중 하나와 함께 상기 기술된 바와 같이 배양하였다. 이들 연구에서, 동일 또는 더 높은 수준의 IFNα가 무결함 C7과 비교하여 중공 캡시드와 불활성 바이러스 벡터 둘 다에 대해 관찰되었다.
상기 인용된 모든 문헌은 참고로써 본원에 포함된다. 수많은 변형 및 변경이 상기 확인된 설명의 범주에 포함되며 당업자에게 명백한 것으로 기대된다. 이러한 조성물 및 공정에 대한 변형 및 변경, 예로써 다른 미니유전자의 선택 또는 벡터 또는 면역 조절자의 선택 또는 투약량은 첨부되는 청구항의 범주 내인 것으로 믿어진다.
SEQUENCE LISTING
<110> The Trustees of the University of Pennsylvania
Roy, Soumitra
Wilson, James M.
Vandenberghe, Luc
<120> Simian Subfamily C Adenoviruses SAdV-40, -31, and -34 and Uses
Thereof
<130> UPN-U4624PCT
<150> US 61/004,465
<151> 2007-11-28
<150> US 61/004,568
<151> 2007-11-28
<150> US 61/004,496
<151> 2007-11-28
<160> 105
<170> PatentIn version 3.5
<210> 1
<211> 37718
<212> DNA
<213> Simian adenovirus 40
<220>
<221> repeat_region
<222> (1)..(113)
<223> label=ITR
<220>
<221> CDS
<222> (2021)..(3541)
<223> label=Elb\55K
<220>
<221> CDS
<222> (3640)..(4098)
<223> label=pIX
<220>
<221> misc_feature
<222> (4163)..(5787)
<223> complement (4163..5496, 5775..5787) label=IVa2
<220>
<221> misc_feature
<222> (5269)..(14219)
<223> complement (5269..8850, 14211..14219) label=pol
<220>
<221> misc_feature
<222> (8652)..(14219)
<223> complement (8652..10652, 14211..14219) label=pTP
<220>
<221> CDS
<222> (11105)..(12361)
<223> label=52K
<220>
<221> CDS
<222> (12388)..(14160)
<223> label=pIIIa
<220>
<221> CDS
<222> (14256)..(16034)
<223> label=penton
<220>
<221> CDS
<222> (16052)..(16645)
<223> label=pVII
<220>
<221> CDS
<222> (16721)..(17833)
<223> label=V
<220>
<221> CDS
<222> (17861)..(18103)
<223> label=pX
<220>
<221> CDS
<222> (18202)..(18954)
<223> label=pVI
<220>
<221> CDS
<222> (19069)..(21948)
<223> label=hexon
<220>
<221> CDS
<222> (21981)..(22607)
<223> label=protease
<220>
<221> misc_feature
<222> (22727)..(24376)
<223> complement label=DBP
<220>
<221> CDS
<222> (24414)..(26915)
<223> label=100K
<220>
<221> CDS
<222> (27607)..(28287)
<223> label=pVIII
<220>
<221> CDS
<222> (28291)..(28605)
<223> label=E3\12.5K
<220>
<221> CDS
<222> (29303)..(29797)
<223> label=E3\gp19K
<220>
<221> CDS
<222> (29829)..(30722)
<223> label=E3\CR1\beta
<220>
<221> CDS
<222> (31576)..(31845)
<223> label=E3\RID\alpha
<220>
<221> CDS
<222> (31851)..(32246)
<223> label=E3\RID\beta
<220>
<221> CDS
<222> (32834)..(34462)
<223> label=fiber
<220>
<221> misc_feature
<222> (34673)..(35830)
<223> complement (34673..34945, 35648..35830) label=E4\orf6/7
<220>
<221> misc_feature
<222> (34949)..(35830)
<223> complement label=E4\orf6
<220>
<221> misc_feature
<222> (35733)..(36095)
<223> complement label=E4\orf4
<220>
<221> misc_feature
<222> (36115)..(36459)
<223> complement label=E4\orf3
<220>
<221> misc_feature
<222> (36459)..(36848)
<223> complement label=E4\orf2
<220>
<221> misc_feature
<222> (36908)..(37291)
<223> complement label=E4\orf1
<220>
<221> repeat_region
<222> (37606)..(37718)
<223> complement label=ITR
<400> 1
catcatcaat aatatacctt attttggatt gaagccaata tgataatgag atgggtggcg 60
cggggcgggg cgcggggcgg gaggcgggtc cgggggcggg ccggcgggcg gggcggtgtg 120
gcggaagtgg actttgtaag tgtggcggat gtgacttgct agtgtcgggc gcggtaaaag 180
tgacgttttc cgtgcgcgac aacgcccacg ggaagtgaca tttttcccgc ggtttttacc 240
ggatgttgta gtgaatttgg gcgtaaccaa gtaagatttg gccattttcg cgggaaaact 300
gaaacgggga agtgaaatct gattaatttc gcgttagtca taccgcgtaa tatttgtcga 360
gggccgaggg actttggccg attacgtgga ggactcgccc aggtgttttt tgaggtgaat 420
ttccgcgttc cgggtcaaag tctccgtttt attattatag tcagctgacg cggagtgtat 480
ttataccctc tgatctcgtc aagaggccac tcttgagtgc cagcgagtag agttttctcc 540
tctgccgctc tccgctccgc tccgctcggc tctgacaccg gggaaaaaat gagacatttc 600
acctacgatg gcggtgtgct caccggccag ctggctgctg aggtcctgga caccctgatc 660
gaggaggtat tggctgataa ttatcctccc tcgactcctt ttgagccacc tacacttcac 720
gaactctacg atctggatgt ggtggggccc agcgatccga acgagcaggc ggtttccagt 780
ttttttccag agtccatgtt gttggccagc caggaggggg tcgaacttga gacccctcct 840
ccgatcgtgg attcccccga tccgccgcag ctgactaggc agcccgagcg ctgtgcggga 900
cctgagacta tgccccagct gctacctgag gtgatcgatc tcacctgtaa tgagtctggt 960
tttccaccca gcgaggatga ggacgaagag ggtgagcagt ttgtgttaga ttctgtggaa 1020
caacccgggc gaggatgcag gtcttgtcaa tatcaccgga aaaacacagg agactcccag 1080
attatgtgtt ctctgtgtta tatgaagatg acctgtatgt ttatttacag taagtttatc 1140
atcggtgggc aggtgggcta tagtgtgggt ggtggtcttt ggggggtttt ttaatatatg 1200
tcaggggtta tgctgaagac ttttttattg tgatttttaa aggtccagtg tctgagcccg 1260
agcaagaacc tgaaccggag cctgagcctt ctcgccccag gagaaagcct gtaatcttaa 1320
ctagacccag cgcaccggta gcgagaggcc tcagcagcgc ggagaccacc gactccggtg 1380
cttcctcatc acccccggag attcaccccc tggtgcccct gtgtcccgtt aagcccgttg 1440
ccgtgagagt cagtgggcgg cggtctgctg tggagtgcat tgaggacttg ctttttgatt 1500
cacaggaacc tttggacttg agcttgaaac gccccaggca ttaaacctgg tcacctggac 1560
tgaatgagtt gacgcctatg tttgcttttg aatgacttaa tgtgtataga taataaagag 1620
tgagataatg ttttaattgc atggtgtgtt taacttgggc ggagtctgct gggtatataa 1680
gcttccctgg gctaaacttg gttacacttg acctcatgga ggcctgggag tgtttggaga 1740
actttgccgg agttcgtgcc ttgctggacg agagctctaa caatacctct tggtggtgga 1800
ggtatttgtg gggctctccc cagggcaagt tagtttgtag aatcaaggag gattacaagt 1860
gggaatttga agagcttttg aaatcctgtg gtgagctatt ggattctttg aatctaggcc 1920
accaggctct cttccaggag aaggtcatca ggactttgga tttttccaca ccggggcgca 1980
ttgcagccgc ggttgctttt ctagcttttt tgaaggatag atg gag cga aga gac 2035
Met Glu Arg Arg Asp
1 5
cca ctt gag ttc ggg cta cgt cct gga ttt tct ggc cat gca act gtg 2083
Pro Leu Glu Phe Gly Leu Arg Pro Gly Phe Ser Gly His Ala Thr Val
10 15 20
gag agc atg gat cag aca caa gaa cag gct gca act gtt gtc ttc cgt 2131
Glu Ser Met Asp Gln Thr Gln Glu Gln Ala Ala Thr Val Val Phe Arg
25 30 35
ccg ccc gtt gct gat tcc ggc gga gga gca aca ggc cgg gtc aga gga 2179
Pro Pro Val Ala Asp Ser Gly Gly Gly Ala Thr Gly Arg Val Arg Gly
40 45 50
ccg ggc ccg tcg gga tcc gga gga gag ggc acc gag gcc ggg cga gag 2227
Pro Gly Pro Ser Gly Ser Gly Gly Glu Gly Thr Glu Ala Gly Arg Glu
55 60 65
gag cgc gct gaa cct ggg aac cgg gct gag cgg cca tcc aca tcg gga 2275
Glu Arg Ala Glu Pro Gly Asn Arg Ala Glu Arg Pro Ser Thr Ser Gly
70 75 80 85
gtg aat gtc ggg cag gtg gtg gat ctt ttt cca gaa ctg cgg cgg att 2323
Val Asn Val Gly Gln Val Val Asp Leu Phe Pro Glu Leu Arg Arg Ile
90 95 100
ttg act att agg gag gat ggg caa ttt gtt aag ggt ctt aag agg gag 2371
Leu Thr Ile Arg Glu Asp Gly Gln Phe Val Lys Gly Leu Lys Arg Glu
105 110 115
agg ggg gct tct gag cat aac gag gag gcc agt aat tta gct ttt agc 2419
Arg Gly Ala Ser Glu His Asn Glu Glu Ala Ser Asn Leu Ala Phe Ser
120 125 130
ttg atg acc aga cac cgt cca gag tgc atc act ttt cag cag att aag 2467
Leu Met Thr Arg His Arg Pro Glu Cys Ile Thr Phe Gln Gln Ile Lys
135 140 145
gac aat tgt gcc aat gag ttg gat ctg ttg ggt cag aag tat agc ata 2515
Asp Asn Cys Ala Asn Glu Leu Asp Leu Leu Gly Gln Lys Tyr Ser Ile
150 155 160 165
gag cag ctg acc act tac tgg ctg cag ccg ggt gat gat ctg gag gaa 2563
Glu Gln Leu Thr Thr Tyr Trp Leu Gln Pro Gly Asp Asp Leu Glu Glu
170 175 180
gct att agg gtg tat gct aag gtg gcc ctg cgg ccc gat tgc aag tac 2611
Ala Ile Arg Val Tyr Ala Lys Val Ala Leu Arg Pro Asp Cys Lys Tyr
185 190 195
aag ctc aag ggg ctg gtg aat atc agg aat tgt tgc tac att tct ggc 2659
Lys Leu Lys Gly Leu Val Asn Ile Arg Asn Cys Cys Tyr Ile Ser Gly
200 205 210
aac ggg gcg gag gtg gag ata gag acc gaa gac agg gtg gct ttc aga 2707
Asn Gly Ala Glu Val Glu Ile Glu Thr Glu Asp Arg Val Ala Phe Arg
215 220 225
tgc agc atg atg aat atg tgg ccg ggg gtg ctg ggc atg gac ggg gtg 2755
Cys Ser Met Met Asn Met Trp Pro Gly Val Leu Gly Met Asp Gly Val
230 235 240 245
gtg att atg aat gtg agg ttc acg ggg ccc aac ttt aac ggc acg gtg 2803
Val Ile Met Asn Val Arg Phe Thr Gly Pro Asn Phe Asn Gly Thr Val
250 255 260
ttt ttg ggg aac acc aac ctg gtc ctg cac ggg gtg agc ttc tat ggg 2851
Phe Leu Gly Asn Thr Asn Leu Val Leu His Gly Val Ser Phe Tyr Gly
265 270 275
ttt aac aac acc tgt gtg gag gcc tgg acc gat gtg aag gtc cgc ggt 2899
Phe Asn Asn Thr Cys Val Glu Ala Trp Thr Asp Val Lys Val Arg Gly
280 285 290
tgc gcc ttt tat gga tgt tgg aag gcc ata gtg agc cgc cct aag agc 2947
Cys Ala Phe Tyr Gly Cys Trp Lys Ala Ile Val Ser Arg Pro Lys Ser
295 300 305
agg agt tcc att aag aaa tgc ttg ttt gag agg tgc acc ttg ggg atc 2995
Arg Ser Ser Ile Lys Lys Cys Leu Phe Glu Arg Cys Thr Leu Gly Ile
310 315 320 325
ctg gcc gag ggc aac tgc agg gtg cgc cac aat gtg gcc tcc gag tgc 3043
Leu Ala Glu Gly Asn Cys Arg Val Arg His Asn Val Ala Ser Glu Cys
330 335 340
ggt tgc ttc atg cta gtc aag agc gtg gcg gta atc aag cat aat atg 3091
Gly Cys Phe Met Leu Val Lys Ser Val Ala Val Ile Lys His Asn Met
345 350 355
gtg tgc ggc aac agc gag gac aag gcc tca cag atg ctg acc tgc acg 3139
Val Cys Gly Asn Ser Glu Asp Lys Ala Ser Gln Met Leu Thr Cys Thr
360 365 370
gat ggc aac tgc cac ttg ctg aag acc atc cat gta acc agc cac agc 3187
Asp Gly Asn Cys His Leu Leu Lys Thr Ile His Val Thr Ser His Ser
375 380 385
cgg aag gcc tgg ccc gtg ttc gag cac aac ttg ctg acc cgc tgc tcc 3235
Arg Lys Ala Trp Pro Val Phe Glu His Asn Leu Leu Thr Arg Cys Ser
390 395 400 405
ttg cat ctg ggc aac agg cgg ggg gtg ttc ctg ccc tat caa tgc aac 3283
Leu His Leu Gly Asn Arg Arg Gly Val Phe Leu Pro Tyr Gln Cys Asn
410 415 420
ttt agt cac acc aag atc ttg cta gag ccc gag agc atg tcc aag gtg 3331
Phe Ser His Thr Lys Ile Leu Leu Glu Pro Glu Ser Met Ser Lys Val
425 430 435
aac ttg aac ggg gtg ttt gac atg acc atg aag atc tgg aag gtg ctg 3379
Asn Leu Asn Gly Val Phe Asp Met Thr Met Lys Ile Trp Lys Val Leu
440 445 450
agg tac gac gag acc agg tcc cgg tgc aga ccc tgc gag tgc ggg ggc 3427
Arg Tyr Asp Glu Thr Arg Ser Arg Cys Arg Pro Cys Glu Cys Gly Gly
455 460 465
aag cat atg agg aac cag ccc gtg atg ctg gat gtg acc gag gag ctg 3475
Lys His Met Arg Asn Gln Pro Val Met Leu Asp Val Thr Glu Glu Leu
470 475 480 485
agg aca gac cac ttg gtt ctg gcc tgc acc agg gcc gag ttt ggt tct 3523
Arg Thr Asp His Leu Val Leu Ala Cys Thr Arg Ala Glu Phe Gly Ser
490 495 500
agc gat gaa gac aca gat tgaggtgggt gagtgggcgt ggcctggggt 3571
Ser Asp Glu Asp Thr Asp
505
ggtcatgaaa atatataagt tgggggtctt agggtctctt tatttgtatt gcagagaccg 3631
ccggagcc atg agc ggg agc agc agc agc agt agc agc agc gcc ttg gat 3681
Met Ser Gly Ser Ser Ser Ser Ser Ser Ser Ser Ala Leu Asp
510 515 520
ggc agc atc gtg agc cct tat ttg acg acg cgg atg ccc cac tgg gcc 3729
Gly Ser Ile Val Ser Pro Tyr Leu Thr Thr Arg Met Pro His Trp Ala
525 530 535
ggg gtg cgt cag aat gtg atg ggc tcc agc atc gac ggc cga ccc gtc 3777
Gly Val Arg Gln Asn Val Met Gly Ser Ser Ile Asp Gly Arg Pro Val
540 545 550
ctg ccc gca aat tcc gcc acg ctg acc tat gcg acc gtc gcg ggg acg 3825
Leu Pro Ala Asn Ser Ala Thr Leu Thr Tyr Ala Thr Val Ala Gly Thr
555 560 565
ccg ttg gac gcc acc gca gcc gcc gcc gcc acc gca gcc gcc tcg gcc 3873
Pro Leu Asp Ala Thr Ala Ala Ala Ala Ala Thr Ala Ala Ala Ser Ala
570 575 580 585
gtg cgc agc ctg gcc acg gac ttt gca ttc ctg gga cca ctg gcg aca 3921
Val Arg Ser Leu Ala Thr Asp Phe Ala Phe Leu Gly Pro Leu Ala Thr
590 595 600
ggg gct act tct cgg gcc gct gct gcc gcc gtt cgc gat gac aag ctg 3969
Gly Ala Thr Ser Arg Ala Ala Ala Ala Ala Val Arg Asp Asp Lys Leu
605 610 615
acc gcc ctg ctg gcg cag ttg gat gcg ctt act cgg gaa ctg ggt gac 4017
Thr Ala Leu Leu Ala Gln Leu Asp Ala Leu Thr Arg Glu Leu Gly Asp
620 625 630
ctt tct cag cag gtc atg gcc ctg cgc cag cag gtc tcc tcc ctg caa 4065
Leu Ser Gln Gln Val Met Ala Leu Arg Gln Gln Val Ser Ser Leu Gln
635 640 645
gct ggc ggg aat gct tct ccc aca aat gcc gtt taagataaat aaaaccagac 4118
Ala Gly Gly Asn Ala Ser Pro Thr Asn Ala Val
650 655 660
tctgtttgga ttaaagaaaa gtagcaagtg cattgctctc tttatttcat aattttccgc 4178
gcgcgatagg ccctagacca gcgttctcgg tcgttgaggg tgcggtgtat cttctccagg 4238
acgtggtaga ggtggctctg gacgttgaga tacatgggca tgagcccgtc ccgggggtgg 4298
aggtagcacc actgcagagc ttcatgctcc ggggtggtgt tgtagatgat ccagtcgtag 4358
caggagcgct gggcatggtg cctaaaaatg tccttcagca gcaggccaat ggccaggggg 4418
aggcccttgg tgtaagtgtt tacaaaacgg ttaagttggg aagggtgcat tcggggagag 4478
atgatgtgca tcttggactg tatttttaga ttggcgatgt ttccgcccag atcccttctg 4538
ggattcatgt tgtgcaggac caccagtaca gtgtatccgg tgcacttggg gaatttgtca 4598
tgcagcttag agggaaaagc gtggaagaac ttggagacgc ccttgtggcc tcccagattt 4658
tccatgcatt cgtccatgat gatggcaatg ggcccgcggg aggcagcttg ggcaaagata 4718
tttctggggt cgctgacgtc gtagttgtgt tccagggtga ggtcgtcata ggccattttt 4778
acaaagcgcg ggcggagggt gcccgactgg gggatgatgg tcccctctgg ccctggggcg 4838
tagttgccct cgcagatctg catttcccag gccttaatct cggagggggg aatcatatcc 4898
acctgcgggg cgatgaagaa aacggtttcc ggagccgggg agattaactg ggatgagagc 4958
aggtttctaa gcagctgtga ttttccacaa ccggtgggcc cataaataac acctataacc 5018
ggttgcagct ggtagtttag agagctgcag ctgccgtcgt cccggaggag gggggccacc 5078
tcgttgagca tgtccctgac gcgcatgttc tccccgacca gatccgccag aaggcgctcg 5138
ccgcccaggg acagcagctc ttgcaaggaa gcaaagtttt tcagcggctt gaggccgtcc 5198
gccgtgggca tgtttttcag ggtctggctg agcagctcca ggcggtccca gagctcggtg 5258
acgtgctcta cggcatctct atccagcata tctcctcgtt tcgcgggttg gggcgacttt 5318
cgctgtaggg taccaagcgg tggtcgtcca gcggggccag agtcatgtcc ttccatgggc 5378
gcagggtcct cgtcagggtg gtctgggtca cggtgaaggg gtgcgctccg ggctgagcgc 5438
ttgccaaggt gcgcttgagg ctggttctgc tggtgctgaa gcgctgccgg tcttcgccct 5498
gcgcgtcggc caggtagcat ttgaccatgg tgtcatagtc cagcccctcc gcggcgtgtc 5558
ccttggcgcg cagcttgccc ttggaggtgg cgccgcacga ggggcagagc aggctcttga 5618
gcgcgtagag cttgggggcg aggaagaccg attcggggga gtaggcgtcc gcgccgcagg 5678
ccccgcacac ggtctcgcac tccaccagcc aggtgagctc ggggcgcgcc gggtcaaaaa 5738
ccaggtttcc cccatgcttt ttgatgcgtt tcttacctcg ggtctccatg aggtggtgtc 5798
cccgctcggt gacgaagagg ctgtccgtgt ctccgtagac cgacttgagg ggtcttttct 5858
ccaagggggt ccctcggtct tcctcgtaga ggaactcgga ccactctgag acgaaggccc 5918
gcgtccaggc caggacgaag gaggctatgt gggaggggta gcggtcgttg tccactaggg 5978
ggtccacctt ttccaaggtg tgaagacaca tgtcgccttc ctcggcgtcc aggaaggtga 6038
ttggcttgta ggtgtaggcc acgtgaccgg gggttcctga cgggggggta taaaaggggg 6098
tgggggcgcg ctcgtcgtca ctctcttccg catcgctgtc tgcgagggcc agctgctggg 6158
gtgagtattc cctctcgaag gcgggcatga cctccgcgct gaggttgtca gtttccaaaa 6218
acgaggagga tttgatgttc acctgtcccg aggtgatacc tttgagggta cccgcgtcca 6278
tctggtcaga aaacacgatc tttttattgt ccagcttggt ggcgaacgac ccgtagaggg 6338
cgttggagag cagcttggcg atggagcgca gggtctggtt cttgtccctg tcggcgcgct 6398
ccttggccgc gatgttgagc tgcacgtact cgcgcgcgac gcagcgccac tcggggaaga 6458
cggtggtgcg ctcgtcgggc accaggcgca cgcgccagcc gcggttgtgc agggtgacca 6518
ggtccacgct ggtggcgacc tcgccgcgca ggcgctcgtt ggtccagcag agacggccgc 6578
ccttgcgcga gcagaagggg ggcagggggt cgagctgggt ctcgtccggg gggtccgcgt 6638
ccacggtgaa gaccccgggg cgcaggcgcg cgtcgaagta gtctatcttg caaccttgca 6698
tgtccagcgc ctgctgccag tcgcgggcgg cgagcgcgcg ctcgtagggg ttgagcggcg 6758
ggccccaggg catggggtgg gtgagtgcgg aggcgtacat gccgcagatg tcatagacgt 6818
agaggggctc ccgcaggacc ccgatgtagg tggggtagca gcggccgccg cggatgctgg 6878
cgcgcacgta gtcatacagc tcgtgcgagg gggcgaggag gtcggggccc aggttggtgc 6938
gggcggggcg ctccgcgcgg aagacgatct gcctgaagat ggcatgtgag ttggaagaga 6998
tggtggggcg ctggaagacg ttgaagctgg cgtcctgcag gccgacggcg tcgcgcacga 7058
aggaggcgta ggagtcgcgc agcttgtgta ccagctcggc ggtgacctgc acgtcgagcg 7118
cgcagtagtc gagggtctcg cggatgatgt catacttagc ctgccccttc tttttccaca 7178
gctcgcggtt gaggacaaac tcttcgcggt ctttccagta ctcttggatc gggaaaccgt 7238
ccggttccga acggtaagag cctagcatgt agaactggtt gacggcctgg taggcgcagc 7298
agcccttctc cacggggagg gcgtaggcct gcgcggcctt gcggagcgag gtgtgggtca 7358
gggcgaaggt gtccctgacc atgactttga ggtactggtg cttgaagtcg gagtcgtcgc 7418
agccgccccg ctcccagagc gagaagtcgg tgcgcttctt ggagcggggg ttgggcagag 7478
cgaaggtgac atcgttgaaa aggattttgc ccgcgcgggg catgaagttg cgggtgatgc 7538
ggaagggccc cggcacttca gagcggttgt tgatgacctg ggcggcgagc acgatctcgt 7598
cgaagccgtt gatgttgtgg cccacgatgt agagttccag gaagcggggc cggcccttta 7658
cggtgggcag cttctttagc tcttcgtagg tgagctcctc gggcgaggcg aggccgtgct 7718
cggccagggc ccagtccgcg aggtgcgggt tgtctctgag gaaggactcc cagaggtcgc 7778
gggccaggag ggtctgcagg cggtccctga aggtcctgaa ctggcggccc acggccattt 7838
tttcgggggt gatgcagtag aaggtgaggg ggtcttgctg ccagcggtcc cagtcgagct 7898
gcagggcgag gtcgcgcgcg gcggtgacca ggcgctcgtc gcccccgaat ttcatgacca 7958
gcatgaaggg cacgagctgc tttccgaagg cccccatcca agtgtaggtc tctacatcgt 8018
aggtgacaaa gaggcgctcc gtgcgaggat gcgagccgat cgggaagaac tggatctccc 8078
gccaccagtt ggaggagtgg ctgttgatgt ggtggaagta gaagtcccgt cgccgggccg 8138
agcactcgtg ctggcttttg taaaagcgag cgcagtactg gcagcgctgc acgggctgta 8198
cctcctgcac gagatgcacc tttcgcccgc gcacgaggaa gccgaggggg aatctgagcc 8258
ccccgcctgg ctcgcggcat ggctggtgct cttctacttt ggatgcgtgt ccgtctccgt 8318
ctggctcctc gaggggtgtt acggtggagc ggaccaccac gccgcgcgag ccgcaggtcc 8378
agatatcggc gcgcggcggt cggagtttga tgacgacatc gcgcagctgg gagctgtcca 8438
tggtctggag ctcccgcggc ggcggcaggt cagccgggag ttcttgcagg ttcacctcgc 8498
agagtcgggc cagggcgcgg ggcaggtcta ggtggtactt gatctctagg ggcgtgttgg 8558
tggcggcgtc gatggcttgc aggagcccgc agccccgggg cgcgacgacg gtgccccgcg 8618
gggtggtggt ggtggtggtg gcggtgcagc tcagaagcgg tgccgcgggc gggcccccgg 8678
aggtaggggg ggctccggtc ccgctggcag gggcggcagc ggcacgtcgg cgtggagcgc 8738
gggcaggagt tggtgctgtg cccggaggtt gctggcgaag gcgacgacgc ggcggttgat 8798
ctcctggatc tggcgcctct gcgtgaagac gacgggcccg gtgagcttga acctgaaaga 8858
gagttcgaca gaatcaatct cggtgtcatt gaccgcggcc tggcgcagga tctcctgcac 8918
gtctcccgag ttgtcttggt aggcgatctc ggccatgaac tgctcgatct cttcctcctg 8978
gaggtctccg cgtccggcgc gttccacggt ggccgccagg tcgttggaga tgcgccccat 9038
gagctgcgag aaggcgttga gtccgccctc gttccagact cggctgtaga ccacgccccc 9098
ctggtcgtcg cgggcgcgca tgaccacctg cgcgaggttg agctccacgt gccgcgcgaa 9158
gacggcgtag ttgcgcagac gctggaagag gtagttgagg gtggtggcgg tgtgctcggc 9218
cacgaagaag ttcatgaccc agcggcgcaa cgtggattcg ttgatgtccc ccaaggcctc 9278
cagccgttcc atggcctcgt agaagtccac ggcgaagttg aaaaactggg agttgcgcgc 9338
cgacacggtc aactcctcct ccagaagacg gatgagctcg gcgacggtgt cgcgcacctc 9398
gcgctcgaag gctatgggga tctcttcctc cgctagcatc accacctcct cctcttcctc 9458
ctcttctggc acttccatga tggcttcctc ctcttcgggg ggtggcggcg gcggcggtgg 9518
gggagggggc gctctgcgcc ggcggcggcg caccgggagg cggtccacga agcgcgcgat 9578
catctccccg cggcggcggc gcatggtctc ggtgacggcg cggccgttct cccgggggcg 9638
cagttggaag acgccgccgg acatctggtg ctggggcggg tggccgtgag gcagcgagac 9698
ggcgctgacg atgcatctca acaattgctg cgtaggtacg ccgccgaggg acctgaggga 9758
gtccatatcc accggatccg aaaacctttc gaggaaggcg tctaaccagt cgcagtcgca 9818
aggtaggctg agcaccgtgg cgggcggcgg ggggtggggg gagtgtctgg cggaggtgct 9878
gctgatgatg taattgaagt aggcggactt gacacggcgg atggtcgaca ggagcaccat 9938
gtccttgggt ccggcctgct ggatgcggag gcggtcggct atgccccagg cttcgttctg 9998
gcatcggcgc aggtccttgt agtagtcttg catgagcctt tccaccggca cctcttctcc 10058
ttcctcttct gcttcttcca tgtctgcttc ggccctgggg cggcgccgcg cccccctgcc 10118
ccccatgcgc gtgaccccga accccctgag cggttggagc agggccaggt cggcgacgac 10178
gcgctcggcc aggatggcct gctgcacctg cgtgagggtg gtttggaagt catccaagtc 10238
cacgaagcgg tggtaggcgc ccgtgttgat ggtgtaggtg cagttggcca tgacggacca 10298
gttgacggtc tggtggcccg gttgcgacat ctcggtgtac ctgagtcgcg agtaggcgcg 10358
ggagtcgaag acgtagtcgt tgcaagtccg caccaggtac tggtagccca ccaggaagtg 10418
cggcggcggc tggcggtaga ggggccagcg cagggtggcg ggggctccgg gggccaggtc 10478
ttccagcatg aggcggtggt aggcgtagat gtacctggac atccaggtga tacccgcggc 10538
ggtggtggag gcgcgcggga agtcgcgcac ccggttccag atgttgcgca ggggcagaaa 10598
gtgctccatg gtaggcgtgc tctgtccagt cagacgcgcg cagtcgttga tactctagac 10658
cagggaaaac gaaagccggt cagcgggcac tcttccgtgg tctggtgaat agatcgcaag 10718
ggtatcatgg cggagggcct cggttcgagc cccgggtccg ggccggacgg tccgccatga 10778
tccacgcggt taccgcccgc gtgtcgaacc caggtgtgcg acgtcagaca acggtggagt 10838
gttccttttg gcgtttttct ggccgggcgc cggcgccgcg taagagacta agccgcgaaa 10898
gcgaaagcag taagtggctc gctccccgta gccggaggga tccttgctaa gggttgcgtt 10958
gcggcgaacc ccggttcgaa tcccgtactc gggccggccg gacccgcggc taaggtgtcg 11018
gattggcctc cccctcgtat aaagaccccg cttgcggatt gactccggac acggggacga 11078
gcccctttta tttttgcttt ccccag atg cat ccg gtg ctg cgg cag atg cgc 11131
Met His Pro Val Leu Arg Gln Met Arg
665
ccc ccg ccc cag cag cag caa caa cac cag caa gag cgg cag caa cag 11179
Pro Pro Pro Gln Gln Gln Gln Gln His Gln Gln Glu Arg Gln Gln Gln
670 675 680 685
cag cgg gag tca tgc agg gcc ccc tca ccc acc ctc ggc ggc ccg gcc 11227
Gln Arg Glu Ser Cys Arg Ala Pro Ser Pro Thr Leu Gly Gly Pro Ala
690 695 700
acc tcg gcg tcc gcg gcc gtg tct ggc gcc tgc ggc ggc ggc ggg ggg 11275
Thr Ser Ala Ser Ala Ala Val Ser Gly Ala Cys Gly Gly Gly Gly Gly
705 710 715
ccg gct gac gac ccc gag gag ccc ccg cgg cgc agg gcc aga cac tac 11323
Pro Ala Asp Asp Pro Glu Glu Pro Pro Arg Arg Arg Ala Arg His Tyr
720 725 730
ctg gac ctg gag gag ggc gag ggc ctg gcg cgg ctg ggg gcg ccg tct 11371
Leu Asp Leu Glu Glu Gly Glu Gly Leu Ala Arg Leu Gly Ala Pro Ser
735 740 745
ccc gag cgc cac ccg cgg gtg cag cta aag cgc gac tcg cgc gag gcg 11419
Pro Glu Arg His Pro Arg Val Gln Leu Lys Arg Asp Ser Arg Glu Ala
750 755 760 765
tac gtg cct cgg cag aac ctg ttc agg gac cgc gcg ggc gag gag ccc 11467
Tyr Val Pro Arg Gln Asn Leu Phe Arg Asp Arg Ala Gly Glu Glu Pro
770 775 780
gag gag atg cgg gac agg agg ttc agc gcg ggg cgg gag ctg cgg cag 11515
Glu Glu Met Arg Asp Arg Arg Phe Ser Ala Gly Arg Glu Leu Arg Gln
785 790 795
ggg ctg aac cgc gag cgg ctg ctg cgc gag gag gac ttt gag ccc gac 11563
Gly Leu Asn Arg Glu Arg Leu Leu Arg Glu Glu Asp Phe Glu Pro Asp
800 805 810
gcg cgg acg ggg atc agc ccc gcg cgc gcg cac gtg gcg gcc gcc gac 11611
Ala Arg Thr Gly Ile Ser Pro Ala Arg Ala His Val Ala Ala Ala Asp
815 820 825
ctg gtg acg gcg tac gag cag acg gtg aac cag gag atc aac ttc caa 11659
Leu Val Thr Ala Tyr Glu Gln Thr Val Asn Gln Glu Ile Asn Phe Gln
830 835 840 845
aag agt ttc aac aac cac gtg cgc acg ctg gtg gcg cgc gag gag gtg 11707
Lys Ser Phe Asn Asn His Val Arg Thr Leu Val Ala Arg Glu Glu Val
850 855 860
act atc ggg ctg atg cac ctg tgg gac ttt gtg agc gcg ctg gtg cag 11755
Thr Ile Gly Leu Met His Leu Trp Asp Phe Val Ser Ala Leu Val Gln
865 870 875
aac ccc aat agc aag cct ctg acg gcg cag ctg ttc ctg ata gtg cag 11803
Asn Pro Asn Ser Lys Pro Leu Thr Ala Gln Leu Phe Leu Ile Val Gln
880 885 890
cac agc agg gac aac gag gcg ttt agg gac gcg ctg ctg aac atc acc 11851
His Ser Arg Asp Asn Glu Ala Phe Arg Asp Ala Leu Leu Asn Ile Thr
895 900 905
gag ccc gag ggc cgg tgg ctg ctg gac ctg att aac atc ctg cag agc 11899
Glu Pro Glu Gly Arg Trp Leu Leu Asp Leu Ile Asn Ile Leu Gln Ser
910 915 920 925
ata gtg gtg cag gag cgc agc ctg agc ctg gcc gac aag gtg gcg gcc 11947
Ile Val Val Gln Glu Arg Ser Leu Ser Leu Ala Asp Lys Val Ala Ala
930 935 940
atc aac tac tcg atg ctg agc ctg ggc aag ttt tac gcg cgc aaa atc 11995
Ile Asn Tyr Ser Met Leu Ser Leu Gly Lys Phe Tyr Ala Arg Lys Ile
945 950 955
tac cag acg ccg tac gtg ccc ata gac aag gag gtg aag atc gac ggt 12043
Tyr Gln Thr Pro Tyr Val Pro Ile Asp Lys Glu Val Lys Ile Asp Gly
960 965 970
ttt tac atg cgc atg gcg ctg aag gtg ctc acc cta agc gac gac ctg 12091
Phe Tyr Met Arg Met Ala Leu Lys Val Leu Thr Leu Ser Asp Asp Leu
975 980 985
ggc gtg tac cgc aac gag cgc atc cac aag gcc gtg agc gtg agc cgg 12139
Gly Val Tyr Arg Asn Glu Arg Ile His Lys Ala Val Ser Val Ser Arg
990 995 1000 1005
cgg cgc gag ctg agc gac cgc gag ctg atg cac agc ctg cag cgg 12184
Arg Arg Glu Leu Ser Asp Arg Glu Leu Met His Ser Leu Gln Arg
1010 1015 1020
gcg ctg gcg ggc gcc ggc agc ggc gac agg gag gcg gag tcc tac 12229
Ala Leu Ala Gly Ala Gly Ser Gly Asp Arg Glu Ala Glu Ser Tyr
1025 1030 1035
ttc gat gcg ggg gcg gac ctg cgc tgg gcg ccc agc cgg cgg gcc 12274
Phe Asp Ala Gly Ala Asp Leu Arg Trp Ala Pro Ser Arg Arg Ala
1040 1045 1050
ctg gag gcc gcg ggg gtc cgc gag gac tat gac gag gac ggc gag 12319
Leu Glu Ala Ala Gly Val Arg Glu Asp Tyr Asp Glu Asp Gly Glu
1055 1060 1065
gag gat gag gag tac gag cta gag gag ggc gag tac ctg gac 12361
Glu Asp Glu Glu Tyr Glu Leu Glu Glu Gly Glu Tyr Leu Asp
1070 1075
taaaccgcgg gtggtgtttc cggtag atg caa gac ccg aac gtg gtg gac 12411
Met Gln Asp Pro Asn Val Val Asp
1080 1085
ccg gcg ctg cgg gcg gct ctg cag agc cag ccg tcc ggc ctt aac 12456
Pro Ala Leu Arg Ala Ala Leu Gln Ser Gln Pro Ser Gly Leu Asn
1090 1095 1100
tcc tca gac gac tgg cga cag gtc atg gac cgc atc atg tcg ctg 12501
Ser Ser Asp Asp Trp Arg Gln Val Met Asp Arg Ile Met Ser Leu
1105 1110 1115
acg gcg cgt aac ccg gac gcg ttc cgg cag cag ccg cag gcc aac 12546
Thr Ala Arg Asn Pro Asp Ala Phe Arg Gln Gln Pro Gln Ala Asn
1120 1125 1130
agg ctc tcc gcc atc ctg gag gcg gtg gtg cct gcg cgc tcg aac 12591
Arg Leu Ser Ala Ile Leu Glu Ala Val Val Pro Ala Arg Ser Asn
1135 1140 1145
ccc acg cac gag aag gtg ctg gcc ata gtg aac gcg ctg gcc gag 12636
Pro Thr His Glu Lys Val Leu Ala Ile Val Asn Ala Leu Ala Glu
1150 1155 1160
aac agg gcc atc cgc ccg gac gag gcc ggg ctg gtg tac gac gcg 12681
Asn Arg Ala Ile Arg Pro Asp Glu Ala Gly Leu Val Tyr Asp Ala
1165 1170 1175
ctg ctg cag cgc gtg gcc cgc tac aac agc ggc aac gtg cag acc 12726
Leu Leu Gln Arg Val Ala Arg Tyr Asn Ser Gly Asn Val Gln Thr
1180 1185 1190
aac ctg gac cgg ctg gtg ggg gac gtg cgc gag gcg gtg gcg cag 12771
Asn Leu Asp Arg Leu Val Gly Asp Val Arg Glu Ala Val Ala Gln
1195 1200 1205
cgc gag cgc gcg gat cgg cag ggc aac ctg ggc tcc atg gtg gcg 12816
Arg Glu Arg Ala Asp Arg Gln Gly Asn Leu Gly Ser Met Val Ala
1210 1215 1220
ctg aat gcc ttc ctg agc acg cag ccg gcc aac gtg ccg cgg ggg 12861
Leu Asn Ala Phe Leu Ser Thr Gln Pro Ala Asn Val Pro Arg Gly
1225 1230 1235
cag gaa gac tac acc aac ttt gtg agc gcg ctg cgg ctg atg gtg 12906
Gln Glu Asp Tyr Thr Asn Phe Val Ser Ala Leu Arg Leu Met Val
1240 1245 1250
acc gag acc ccc cag agc gag gtg tac cag tcg ggc ccg gac tac 12951
Thr Glu Thr Pro Gln Ser Glu Val Tyr Gln Ser Gly Pro Asp Tyr
1255 1260 1265
ttc ttc cag acc agc aga cag ggc ctg cag acg gtg aac ctg agc 12996
Phe Phe Gln Thr Ser Arg Gln Gly Leu Gln Thr Val Asn Leu Ser
1270 1275 1280
cag gct ttc aag aac ctg cgg ggg ctg tgg ggc gtg aag gcg ccc 13041
Gln Ala Phe Lys Asn Leu Arg Gly Leu Trp Gly Val Lys Ala Pro
1285 1290 1295
acc ggc gac cgg gcg acg gtg tcc agc ctg ctg acg ccc aac tcg 13086
Thr Gly Asp Arg Ala Thr Val Ser Ser Leu Leu Thr Pro Asn Ser
1300 1305 1310
cgc ctg ctg ctg ctg ctg atc gcg ccg ttc acg gac agc ggc agc 13131
Arg Leu Leu Leu Leu Leu Ile Ala Pro Phe Thr Asp Ser Gly Ser
1315 1320 1325
gtg tcc cgg gac acc tac ctg ggg cac ctg ctg acc ctg tac cgc 13176
Val Ser Arg Asp Thr Tyr Leu Gly His Leu Leu Thr Leu Tyr Arg
1330 1335 1340
gag gcc atc ggg cag gcg cag gtg gac gag cac acc ttc cag gag 13221
Glu Ala Ile Gly Gln Ala Gln Val Asp Glu His Thr Phe Gln Glu
1345 1350 1355
atc acc agc gtt agc cgc gcg ctg ggg cag gag gac acg agc agc 13266
Ile Thr Ser Val Ser Arg Ala Leu Gly Gln Glu Asp Thr Ser Ser
1360 1365 1370
ctg gag gcg act ctg aac tac ctg ctg acc aac cgg cgg cag aag 13311
Leu Glu Ala Thr Leu Asn Tyr Leu Leu Thr Asn Arg Arg Gln Lys
1375 1380 1385
att ccc tcg ctg cac agc ctg acc tcc gag gag gag cgc atc ttg 13356
Ile Pro Ser Leu His Ser Leu Thr Ser Glu Glu Glu Arg Ile Leu
1390 1395 1400
cgc tac gtg cag cag agc gtg agc ctg aac ctg atg cgc gac ggg 13401
Arg Tyr Val Gln Gln Ser Val Ser Leu Asn Leu Met Arg Asp Gly
1405 1410 1415
gtg acg ccc agt gtg gcg ctg gac atg acc gcg cgc aac atg gaa 13446
Val Thr Pro Ser Val Ala Leu Asp Met Thr Ala Arg Asn Met Glu
1420 1425 1430
ccg ggc atg tac gcc gcg cac cgg cct tac atc aac cgc ctg atg 13491
Pro Gly Met Tyr Ala Ala His Arg Pro Tyr Ile Asn Arg Leu Met
1435 1440 1445
gac tac ctg cat cgc gcg gcg gcc gtg aac ccc gag tac ttt acc 13536
Asp Tyr Leu His Arg Ala Ala Ala Val Asn Pro Glu Tyr Phe Thr
1450 1455 1460
aac gcc atc ctg aac ccg cac tgg ctc ccg ccg ccc ggg ttc tac 13581
Asn Ala Ile Leu Asn Pro His Trp Leu Pro Pro Pro Gly Phe Tyr
1465 1470 1475
agc ggg ggc ttc gag gtc ccg gag gcc aac gat ggc ttc ctg tgg 13626
Ser Gly Gly Phe Glu Val Pro Glu Ala Asn Asp Gly Phe Leu Trp
1480 1485 1490
gac gac atg gac gac agc gtg ttc tcc ccg cgg ccg cag gcg ctg 13671
Asp Asp Met Asp Asp Ser Val Phe Ser Pro Arg Pro Gln Ala Leu
1495 1500 1505
gcg gaa gcg tcc ctg ctg cgt ccc aag aag gag gag gag gcg agt 13716
Ala Glu Ala Ser Leu Leu Arg Pro Lys Lys Glu Glu Glu Ala Ser
1510 1515 1520
cgc cgc cgc ggc agc agc ggc gtg gct tct ctg tcc gag ctg ggg 13761
Arg Arg Arg Gly Ser Ser Gly Val Ala Ser Leu Ser Glu Leu Gly
1525 1530 1535
gcg gca gcc gcc gcg cgc ccc ggg tcc ctg ggc ggc agc ccc ttt 13806
Ala Ala Ala Ala Ala Arg Pro Gly Ser Leu Gly Gly Ser Pro Phe
1540 1545 1550
ccg agc ctg gtg ggg tct ctg cac agc gag cgc acc acc cgc cct 13851
Pro Ser Leu Val Gly Ser Leu His Ser Glu Arg Thr Thr Arg Pro
1555 1560 1565
cgg ctg ctg ggc gag gac gag tac ctg aat aac tcc ctg ctg cag 13896
Arg Leu Leu Gly Glu Asp Glu Tyr Leu Asn Asn Ser Leu Leu Gln
1570 1575 1580
ccg gtg cgg gag aaa aac ctg ccc ccc gcc ttc ccc aac aac ggg 13941
Pro Val Arg Glu Lys Asn Leu Pro Pro Ala Phe Pro Asn Asn Gly
1585 1590 1595
ata gag agc ctg gtg gac aag atg agc aga tgg aag acc tat gcg 13986
Ile Glu Ser Leu Val Asp Lys Met Ser Arg Trp Lys Thr Tyr Ala
1600 1605 1610
cag gag cac agg gac gcg ccc gcg ctc cgg ccg ccc acg cgg cgc 14031
Gln Glu His Arg Asp Ala Pro Ala Leu Arg Pro Pro Thr Arg Arg
1615 1620 1625
cag cgc cac gac cgg cag cgg ggg ctg gtg tgg gat gac gag gac 14076
Gln Arg His Asp Arg Gln Arg Gly Leu Val Trp Asp Asp Glu Asp
1630 1635 1640
tcc gcg gac gat agc agc gtg ctg gac ctg gga ggg agc ggc aac 14121
Ser Ala Asp Asp Ser Ser Val Leu Asp Leu Gly Gly Ser Gly Asn
1645 1650 1655
ccg ttc gcg cac ctg cgc ccc cgc ctg ggg agg atg ttt taaaaaaaaa 14170
Pro Phe Ala His Leu Arg Pro Arg Leu Gly Arg Met Phe
1660 1665 1670
aaaaagcaag aagcatgatg caaaattaaa taaaactcac caaggccatg gcgaccgagc 14230
gttggtttct tgtgttccct tcagt atg cgg cgc gcg gcg atg tac cag gag 14282
Met Arg Arg Ala Ala Met Tyr Gln Glu
1675
gga cct cct ccc tct tac gag agc gtg gtg ggc gcg gcg gcg gcg 14327
Gly Pro Pro Pro Ser Tyr Glu Ser Val Val Gly Ala Ala Ala Ala
1680 1685 1690
gcg ccc tct tct ccc ttt gcg tcg cag ctg ctg gag ccg ccg tac 14372
Ala Pro Ser Ser Pro Phe Ala Ser Gln Leu Leu Glu Pro Pro Tyr
1695 1700 1705
gtg cct ccg cgc tac ctg cgg cct acg ggg ggg aga aac agc atc 14417
Val Pro Pro Arg Tyr Leu Arg Pro Thr Gly Gly Arg Asn Ser Ile
1710 1715 1720
cgt tac tcg gag ctg gcg ccc ctg ttc gac acc acc cgg gtg tac 14462
Arg Tyr Ser Glu Leu Ala Pro Leu Phe Asp Thr Thr Arg Val Tyr
1725 1730 1735
ctg gtg gac aac aag tcg gcg gac gtg gcc tcc ctg aac tac cag 14507
Leu Val Asp Asn Lys Ser Ala Asp Val Ala Ser Leu Asn Tyr Gln
1740 1745 1750
aac gac cac agc aat ttt ttg acc acg gtc atc cag aac aat gac 14552
Asn Asp His Ser Asn Phe Leu Thr Thr Val Ile Gln Asn Asn Asp
1755 1760 1765
tac agc ccg agc gag gcc agc acc cag acc atc aat ctg gat gac 14597
Tyr Ser Pro Ser Glu Ala Ser Thr Gln Thr Ile Asn Leu Asp Asp
1770 1775 1780
cgg tcg cac tgg ggc ggc gac ctg aaa acc atc ctg cac acc aac 14642
Arg Ser His Trp Gly Gly Asp Leu Lys Thr Ile Leu His Thr Asn
1785 1790 1795
atg ccc aac gtg aac gag ttc atg ttc acc aat aag ttc aag gcg 14687
Met Pro Asn Val Asn Glu Phe Met Phe Thr Asn Lys Phe Lys Ala
1800 1805 1810
cgg gtg atg gtg tcg cgc tcg cac acc aag gaa gac cgg gtg gag 14732
Arg Val Met Val Ser Arg Ser His Thr Lys Glu Asp Arg Val Glu
1815 1820 1825
ctg aag tac gag tgg gtg gag ttc gag ctg cca gag ggc aac tac 14777
Leu Lys Tyr Glu Trp Val Glu Phe Glu Leu Pro Glu Gly Asn Tyr
1830 1835 1840
tcc gag acc atg acc att gac ctg atg aac aac gcg atc gtg gag 14822
Ser Glu Thr Met Thr Ile Asp Leu Met Asn Asn Ala Ile Val Glu
1845 1850 1855
cac tat ctg aaa gtg ggc agg cag aac ggg gtc ctg gag agc gac 14867
His Tyr Leu Lys Val Gly Arg Gln Asn Gly Val Leu Glu Ser Asp
1860 1865 1870
atc ggg gtc aag ttc gac acc agg aac ttc cgc ctg ggg ctg gac 14912
Ile Gly Val Lys Phe Asp Thr Arg Asn Phe Arg Leu Gly Leu Asp
1875 1880 1885
ccc gtg acc ggg ctg gtt atg ccc ggg gtg tac acc aac gag gcc 14957
Pro Val Thr Gly Leu Val Met Pro Gly Val Tyr Thr Asn Glu Ala
1890 1895 1900
ttc cat ccc gac atc atc ctg ctg ccc ggc tgc ggg gtg gac ttc 15002
Phe His Pro Asp Ile Ile Leu Leu Pro Gly Cys Gly Val Asp Phe
1905 1910 1915
act tac agc cgc ctg agc aac ctc ctg ggc atc cgc aag cgg cag 15047
Thr Tyr Ser Arg Leu Ser Asn Leu Leu Gly Ile Arg Lys Arg Gln
1920 1925 1930
ccc ttc cag gag ggc ttc agg atc acc tac gag gac ctg gag ggg 15092
Pro Phe Gln Glu Gly Phe Arg Ile Thr Tyr Glu Asp Leu Glu Gly
1935 1940 1945
ggc aac atc ccc gcg ctc ctc gat gtg gag gcc tac cag gat agc 15137
Gly Asn Ile Pro Ala Leu Leu Asp Val Glu Ala Tyr Gln Asp Ser
1950 1955 1960
ttg aag gaa aat gag gcg gga cag gag gat acc gcc ccc gcc gcc 15182
Leu Lys Glu Asn Glu Ala Gly Gln Glu Asp Thr Ala Pro Ala Ala
1965 1970 1975
tcc gcc gcc gcc gag cag ggc gag gat gct gct gac acc gcg gcc 15227
Ser Ala Ala Ala Glu Gln Gly Glu Asp Ala Ala Asp Thr Ala Ala
1980 1985 1990
gcg gac ggg gca gag gcc gac ccc gct atg gtg gtg gag gct ccc 15272
Ala Asp Gly Ala Glu Ala Asp Pro Ala Met Val Val Glu Ala Pro
1995 2000 2005
gag cag gag gag gac atg aat gac agt gcg gtg cgc gga gac acc 15317
Glu Gln Glu Glu Asp Met Asn Asp Ser Ala Val Arg Gly Asp Thr
2010 2015 2020
ttc gtc acc cgg ggg gag gaa aag caa gcg gag gcc gag gcc gcg 15362
Phe Val Thr Arg Gly Glu Glu Lys Gln Ala Glu Ala Glu Ala Ala
2025 2030 2035
gcc gag gaa aag caa ctg gcg gca gca gcg gcg gcg gcg gcg ttg 15407
Ala Glu Glu Lys Gln Leu Ala Ala Ala Ala Ala Ala Ala Ala Leu
2040 2045 2050
gcc gcg gcg gag gct gag tct gag ggg acc aag ccc gcc aag gag 15452
Ala Ala Ala Glu Ala Glu Ser Glu Gly Thr Lys Pro Ala Lys Glu
2055 2060 2065
ccc gtg att aag ccc ctg acc gaa gat agc aag aag cgc agt tac 15497
Pro Val Ile Lys Pro Leu Thr Glu Asp Ser Lys Lys Arg Ser Tyr
2070 2075 2080
aac ctg ctc aag gac agc acc aac acc gcg tac cgc agc tgg tac 15542
Asn Leu Leu Lys Asp Ser Thr Asn Thr Ala Tyr Arg Ser Trp Tyr
2085 2090 2095
ctg gcc tac aac tac ggc gac ccg tcg acg ggg gtg cgc tcc tgg 15587
Leu Ala Tyr Asn Tyr Gly Asp Pro Ser Thr Gly Val Arg Ser Trp
2100 2105 2110
acc ctg ctg tgc acg ccg gac gtg acc tgc ggc tcg gag cag gtg 15632
Thr Leu Leu Cys Thr Pro Asp Val Thr Cys Gly Ser Glu Gln Val
2115 2120 2125
tac tgg tcg ctg ccc gac atg atg caa gac ccc gtg acc ttc cgc 15677
Tyr Trp Ser Leu Pro Asp Met Met Gln Asp Pro Val Thr Phe Arg
2130 2135 2140
tcc acg cgg cag gtc agc aac ttc ccg gtg gtg ggc gcc gag ctg 15722
Ser Thr Arg Gln Val Ser Asn Phe Pro Val Val Gly Ala Glu Leu
2145 2150 2155
ctg ccc gtg cac tcc aag agc ttc tac aac gac cag gcc gtc tac 15767
Leu Pro Val His Ser Lys Ser Phe Tyr Asn Asp Gln Ala Val Tyr
2160 2165 2170
tcc cag ctc atc cgc cag ttc acc tct ctg acc cac gtg ttc aat 15812
Ser Gln Leu Ile Arg Gln Phe Thr Ser Leu Thr His Val Phe Asn
2175 2180 2185
cgc ttt cct gag aac cag att ctg gcg cgc ccg ccc gcc ccc acc 15857
Arg Phe Pro Glu Asn Gln Ile Leu Ala Arg Pro Pro Ala Pro Thr
2190 2195 2200
atc acc acc gtc agt gaa aac gtt cct gct ctc aca gat cac ggg 15902
Ile Thr Thr Val Ser Glu Asn Val Pro Ala Leu Thr Asp His Gly
2205 2210 2215
acg cta ccg ctg cgc aac agc atc gga gga gtc cag cga gtg acc 15947
Thr Leu Pro Leu Arg Asn Ser Ile Gly Gly Val Gln Arg Val Thr
2220 2225 2230
gtt act gac gcc aga cgc cgc acc tgc ccc tac gtt tac aag gcc 15992
Val Thr Asp Ala Arg Arg Arg Thr Cys Pro Tyr Val Tyr Lys Ala
2235 2240 2245
ttg ggc ata gtc tcg ccg cgc gtc ctt tcc agc cgc act ttt 16034
Leu Gly Ile Val Ser Pro Arg Val Leu Ser Ser Arg Thr Phe
2250 2255 2260
tgagcaacac caccatc atg tcc atc ctg atc tca ccc agc aat aac tcc 16084
Met Ser Ile Leu Ile Ser Pro Ser Asn Asn Ser
2265 2270
ggc tgg gga ctg ctg cgc gcg ccc agc aag atg ttc gga ggg gcg 16129
Gly Trp Gly Leu Leu Arg Ala Pro Ser Lys Met Phe Gly Gly Ala
2275 2280 2285
agg aag cgt tcc gag cag cac ccc gtg cgc gtg cgc ggg cac ttc 16174
Arg Lys Arg Ser Glu Gln His Pro Val Arg Val Arg Gly His Phe
2290 2295 2300
cgc gcc ccc tgg gga gcg cac aaa cgc ggc cgc gcg ggg cgc acc 16219
Arg Ala Pro Trp Gly Ala His Lys Arg Gly Arg Ala Gly Arg Thr
2305 2310 2315
acc gtg gac gac gcc atc gac tcg gtg gtg gag cag gcg cgc aac 16264
Thr Val Asp Asp Ala Ile Asp Ser Val Val Glu Gln Ala Arg Asn
2320 2325 2330
tac agg ccc gcg gtc tct acc gtg gac gcg gcc atc cag acc gtg 16309
Tyr Arg Pro Ala Val Ser Thr Val Asp Ala Ala Ile Gln Thr Val
2335 2340 2345
gtg cgg ggc gcg cgg cgg tac gcc aag ctg aag agc cgc cgg aag 16354
Val Arg Gly Ala Arg Arg Tyr Ala Lys Leu Lys Ser Arg Arg Lys
2350 2355 2360
cgc gtg gcc cgc cgc cac cgc cgc cga ccc ggg gcc gcc gcc aaa 16399
Arg Val Ala Arg Arg His Arg Arg Arg Pro Gly Ala Ala Ala Lys
2365 2370 2375
cgc gcc gcc gcg gcc ctg ctt cgc cgg gcc aag cgc acg ggc cgc 16444
Arg Ala Ala Ala Ala Leu Leu Arg Arg Ala Lys Arg Thr Gly Arg
2380 2385 2390
cgc gcc gcc atg agg gcc gcg cgc cgc ttg gcc gcc ggc atc acc 16489
Arg Ala Ala Met Arg Ala Ala Arg Arg Leu Ala Ala Gly Ile Thr
2395 2400 2405
gcc gcc acc atg gcc ccc cgt acc cga aga cgc gcg gcc gcc gcc 16534
Ala Ala Thr Met Ala Pro Arg Thr Arg Arg Arg Ala Ala Ala Ala
2410 2415 2420
gcc gcc gcc gcc atc agt gac atg gcc agc agg cgc cgg ggc aac 16579
Ala Ala Ala Ala Ile Ser Asp Met Ala Ser Arg Arg Arg Gly Asn
2425 2430 2435
gtg tac tgg gtg cgc gac tcg gtg acc ggc acg cgc gtg ccc gtg 16624
Val Tyr Trp Val Arg Asp Ser Val Thr Gly Thr Arg Val Pro Val
2440 2445 2450
cgc ttc cgc ccc ccg cgg act tgagatgatg tgaaaaaaca acactgagtc 16675
Arg Phe Arg Pro Pro Arg Thr
2455 2460
tcctgctgtt gtgtgtatcc cagcggcggc ggcgcgcgca gcgtc atg tcc aag 16729
Met Ser Lys
cgc aaa atc aaa gaa gag atg ctc cag gtc gtc gcg ccg gag atc 16774
Arg Lys Ile Lys Glu Glu Met Leu Gln Val Val Ala Pro Glu Ile
2465 2470 2475
tat ggg ccc ccg aag aag gaa gag cag gat tcg aag ccc cgc aag 16819
Tyr Gly Pro Pro Lys Lys Glu Glu Gln Asp Ser Lys Pro Arg Lys
2480 2485 2490
ata aag cgg gtc aaa aag aaa aag aaa gat gat gac gat gcc gat 16864
Ile Lys Arg Val Lys Lys Lys Lys Lys Asp Asp Asp Asp Ala Asp
2495 2500 2505
ggg gag gtg gag ttc ctg cgc gcc acg gcg ccc agg cgc ccg gtg 16909
Gly Glu Val Glu Phe Leu Arg Ala Thr Ala Pro Arg Arg Pro Val
2510 2515 2520
cag tgg aag ggc cgg cgc gta aag cgc gtc ctg cgc ccc ggc acc 16954
Gln Trp Lys Gly Arg Arg Val Lys Arg Val Leu Arg Pro Gly Thr
2525 2530 2535
gcg gtg gtc ttc acg ccc ggc gag cgc tcc acc cgg act ttc aag 16999
Ala Val Val Phe Thr Pro Gly Glu Arg Ser Thr Arg Thr Phe Lys
2540 2545 2550
cgc gtc tat gac gag gtg tac ggc gac gaa gac ctg ctg gag cag 17044
Arg Val Tyr Asp Glu Val Tyr Gly Asp Glu Asp Leu Leu Glu Gln
2555 2560 2565
gcc aac gag cgc ttc gga gag ttt gct tac ggg aag cgt cag cgg 17089
Ala Asn Glu Arg Phe Gly Glu Phe Ala Tyr Gly Lys Arg Gln Arg
2570 2575 2580
gcg ctg ggg aag gag gac ctg ctg gcg ctg ccg ctg gac cag ggc 17134
Ala Leu Gly Lys Glu Asp Leu Leu Ala Leu Pro Leu Asp Gln Gly
2585 2590 2595
aac ccc acc ccc agt ctg aag ccc gtg acc ctg cag cag gtg ctg 17179
Asn Pro Thr Pro Ser Leu Lys Pro Val Thr Leu Gln Gln Val Leu
2600 2605 2610
ccg agc agc gca ccc tcc gag gcg aag cgg ggt ctg aag cgc gag 17224
Pro Ser Ser Ala Pro Ser Glu Ala Lys Arg Gly Leu Lys Arg Glu
2615 2620 2625
ggc ggc gac ctg gcg ccc acc gtg cag ctc atg gtg ccc aag cgg 17269
Gly Gly Asp Leu Ala Pro Thr Val Gln Leu Met Val Pro Lys Arg
2630 2635 2640
cag agg ctg gag gat gtg ctg gag aaa atg aaa gta gac ccc ggt 17314
Gln Arg Leu Glu Asp Val Leu Glu Lys Met Lys Val Asp Pro Gly
2645 2650 2655
ctg cag ccg gac atc agg gtc cgc ccc atc aag cag gtg gcg ccg 17359
Leu Gln Pro Asp Ile Arg Val Arg Pro Ile Lys Gln Val Ala Pro
2660 2665 2670
ggc ctc ggc gtg cag acc gtg gac gtg gtc atc ccc acc ggc aac 17404
Gly Leu Gly Val Gln Thr Val Asp Val Val Ile Pro Thr Gly Asn
2675 2680 2685
tcc ccc gcc gcc acc acc act acc gct gcc tcc acg gac atg gag 17449
Ser Pro Ala Ala Thr Thr Thr Thr Ala Ala Ser Thr Asp Met Glu
2690 2695 2700
aca cag acc gat ccc gcc gca gcc gca gcc gcc gcc gca gcc gcg 17494
Thr Gln Thr Asp Pro Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
2705 2710 2715
acc tcc tcg gcg gag gtg cag acg gac ccc tgg ctg ccg ccg gcg 17539
Thr Ser Ser Ala Glu Val Gln Thr Asp Pro Trp Leu Pro Pro Ala
2720 2725 2730
atg tca gct ccc cgc gcg cgt cgc ggg cgc agg aag tac ggc gcc 17584
Met Ser Ala Pro Arg Ala Arg Arg Gly Arg Arg Lys Tyr Gly Ala
2735 2740 2745
gcc aac gcg ctc ctg ccc gag tac gcc ttg cat cct tcc atc gcg 17629
Ala Asn Ala Leu Leu Pro Glu Tyr Ala Leu His Pro Ser Ile Ala
2750 2755 2760
ccc acc ccc ggc tac cga ggc tat acc tac cgc ccg cga aga gcc 17674
Pro Thr Pro Gly Tyr Arg Gly Tyr Thr Tyr Arg Pro Arg Arg Ala
2765 2770 2775
aag ggt tcc acc cgc cgt ccc cgc cga cgc gcc gcc gcc acc acc 17719
Lys Gly Ser Thr Arg Arg Pro Arg Arg Arg Ala Ala Ala Thr Thr
2780 2785 2790
cgc cgc cgc cgc cgc aga cgc cag ccc gca ctg gct cca gtc tcc 17764
Arg Arg Arg Arg Arg Arg Arg Gln Pro Ala Leu Ala Pro Val Ser
2795 2800 2805
gtg agg aga gtg gcg cgc gac gga cac acc ctg gtg ctg ccc agg 17809
Val Arg Arg Val Ala Arg Asp Gly His Thr Leu Val Leu Pro Arg
2810 2815 2820
gcg cgc tac cac ccc agc atc gtt taaaagcctg ttgtggttct tgcagat 17860
Ala Arg Tyr His Pro Ser Ile Val
2825 2830
atg gcc ctc act tgc cgc ctc cgt ttc ccg gtg ccg gga tac cga 17905
Met Ala Leu Thr Cys Arg Leu Arg Phe Pro Val Pro Gly Tyr Arg
2835 2840 2845
gga gga aga tcg cgc cgc agg agg ggt ctg gcc ggc cgc ggc ctg 17950
Gly Gly Arg Ser Arg Arg Arg Arg Gly Leu Ala Gly Arg Gly Leu
2850 2855 2860
agc gga ggc agc cgc cgc gcg cac cgg cgg cga cgc gcc acc agc 17995
Ser Gly Gly Ser Arg Arg Ala His Arg Arg Arg Arg Ala Thr Ser
2865 2870 2875
cga cgc atg cgc ggc ggg gtg ctg ccc ctg tta atc ccc ctg atc 18040
Arg Arg Met Arg Gly Gly Val Leu Pro Leu Leu Ile Pro Leu Ile
2880 2885 2890
gcc gcg gcg atc ggc gcc gtg ccc ggg atc gcc tcc gtg gcc ttg 18085
Ala Ala Ala Ile Gly Ala Val Pro Gly Ile Ala Ser Val Ala Leu
2895 2900 2905
caa gcg tcc cag agg cat tgacagactt gcaaacttgc aaatatggaa 18133
Gln Ala Ser Gln Arg His
2910
aaaaaaaaaa accccaataa aaaagtctag actctcacgc tcgcttggtc ctgtgactat 18193
tttgtaga atg gaa gac atc aac ttt gcg tcg ctg gcc ccg cgt cac 18240
Met Glu Asp Ile Asn Phe Ala Ser Leu Ala Pro Arg His
2915 2920 2925
ggc tcg cgc ccg ttc ctg gga cac tgg aac gat atc ggc acc agc 18285
Gly Ser Arg Pro Phe Leu Gly His Trp Asn Asp Ile Gly Thr Ser
2930 2935 2940
aac atg agc ggt ggc gcc ttc agt tgg ggc tct ctg tgg agc ggc 18330
Asn Met Ser Gly Gly Ala Phe Ser Trp Gly Ser Leu Trp Ser Gly
2945 2950 2955
att aaa agt atc ggg tct gcc gtt aaa aat tac ggc tcc cgg gcc 18375
Ile Lys Ser Ile Gly Ser Ala Val Lys Asn Tyr Gly Ser Arg Ala
2960 2965 2970
tgg aac agc agc acg ggc cag atg ttg aga gac aag ttg aaa gag 18420
Trp Asn Ser Ser Thr Gly Gln Met Leu Arg Asp Lys Leu Lys Glu
2975 2980 2985
cag aac ttc cag cag aag gtg gtg gag ggc ctg gcc tcc ggc atc 18465
Gln Asn Phe Gln Gln Lys Val Val Glu Gly Leu Ala Ser Gly Ile
2990 2995 3000
aac ggg gtg gtg gac ctg gcc aac cag gcc gtg cag aat aag atc 18510
Asn Gly Val Val Asp Leu Ala Asn Gln Ala Val Gln Asn Lys Ile
3005 3010 3015
aac agc aga ctg gac ccc cgg ccg ccg gtg gag gag gtg ccg ccg 18555
Asn Ser Arg Leu Asp Pro Arg Pro Pro Val Glu Glu Val Pro Pro
3020 3025 3030
gcg ctg gag acg gtg tcc ccc gat ggg cgt ggc gag aag cgc ccg 18600
Ala Leu Glu Thr Val Ser Pro Asp Gly Arg Gly Glu Lys Arg Pro
3035 3040 3045
cgg ccc gat agg gaa gag acc act ctg gtc acg cag acc gat gag 18645
Arg Pro Asp Arg Glu Glu Thr Thr Leu Val Thr Gln Thr Asp Glu
3050 3055 3060
ccg ccc ccg tat gag gag gcc ctg aag caa ggt ctg ccc acc acg 18690
Pro Pro Pro Tyr Glu Glu Ala Leu Lys Gln Gly Leu Pro Thr Thr
3065 3070 3075
cgg ccc atc gcg ccc atg gcc acc ggg gtg gtg ggc cgc cac acc 18735
Arg Pro Ile Ala Pro Met Ala Thr Gly Val Val Gly Arg His Thr
3080 3085 3090
ccc gcc acg ctg gac ttg cct ccg ccc gcc gat gtg ccg cag cag 18780
Pro Ala Thr Leu Asp Leu Pro Pro Pro Ala Asp Val Pro Gln Gln
3095 3100 3105
cag aag gcg gca cag ccg ggc ccg ccc gcg acc gcc tcc cgt tcc 18825
Gln Lys Ala Ala Gln Pro Gly Pro Pro Ala Thr Ala Ser Arg Ser
3110 3115 3120
tcc gcc ggt cct ctg cgc cgc gcg gcc agc ggc ccc cgc ggg ggg 18870
Ser Ala Gly Pro Leu Arg Arg Ala Ala Ser Gly Pro Arg Gly Gly
3125 3130 3135
gtc gcg agg cac ggc aac tgg cag agc acg ctg aac agc atc gtg 18915
Val Ala Arg His Gly Asn Trp Gln Ser Thr Leu Asn Ser Ile Val
3140 3145 3150
ggt ctg ggg gtg cgg tcc gtg aag cgc cgc cga tgc tac tgaatagctt 18964
Gly Leu Gly Val Arg Ser Val Lys Arg Arg Arg Cys Tyr
3155 3160
agctaacgtg ttgtatgtgt gtatgcgccc tatgtcgccg ccagaggagc tgctgagtcg 19024
ccgccgttcg cgcgcccacc accaccgcca ctccgcccct caag atg gcg acc cca 19080
Met Ala Thr Pro
3165
tcg atg atg ccg cag tgg tcg tac atg cac atc tcg ggc cag gac 19125
Ser Met Met Pro Gln Trp Ser Tyr Met His Ile Ser Gly Gln Asp
3170 3175 3180
gcc tcg gag tac ctg agc ccc ggg ctg gtg cag ttc gcc cgc gcc 19170
Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala Arg Ala
3185 3190 3195
acc gag agc tac ttc agc ctg agt aac aag ttt agg aac ccc acg 19215
Thr Glu Ser Tyr Phe Ser Leu Ser Asn Lys Phe Arg Asn Pro Thr
3200 3205 3210
gtg gcg ccc acg cac gat gtg acc acc gac cgg tct cag cgc ctg 19260
Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
3215 3220 3225
acg ctg cgg ttc att ccc gtg gac cgc gag gac acc gcg tac tcg 19305
Thr Leu Arg Phe Ile Pro Val Asp Arg Glu Asp Thr Ala Tyr Ser
3230 3235 3240
tac aag gcg cgg ttc acc ctg gcc gtg ggc gac aac cgc gtg ctg 19350
Tyr Lys Ala Arg Phe Thr Leu Ala Val Gly Asp Asn Arg Val Leu
3245 3250 3255
gac atg gcc tcc acc tac ttt gac atc cgc ggg gtg ctg gac cgg 19395
Asp Met Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg
3260 3265 3270
ggt ccc act ttc aag ccc tac tct ggc acc gcc tac aac tcc ctg 19440
Gly Pro Thr Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu
3275 3280 3285
gcc ccc aag ggc gct ccc aac tcc tgc gag tgg gag caa gag gaa 19485
Ala Pro Lys Gly Ala Pro Asn Ser Cys Glu Trp Glu Gln Glu Glu
3290 3295 3300
act cag gca gtt gaa gaa gca gca gaa gag gaa gaa gaa gat gct 19530
Thr Gln Ala Val Glu Glu Ala Ala Glu Glu Glu Glu Glu Asp Ala
3305 3310 3315
gac ggt caa gct gag gaa gag caa gca gct acc aaa aag act cat 19575
Asp Gly Gln Ala Glu Glu Glu Gln Ala Ala Thr Lys Lys Thr His
3320 3325 3330
gta tat gct cag gct ccc ctt tct ggc gaa aaa att agt aaa gat 19620
Val Tyr Ala Gln Ala Pro Leu Ser Gly Glu Lys Ile Ser Lys Asp
3335 3340 3345
ggt ctg caa ata gga acg gac gct aca gct aca gaa caa aaa cct 19665
Gly Leu Gln Ile Gly Thr Asp Ala Thr Ala Thr Glu Gln Lys Pro
3350 3355 3360
att tat gca gac cct aca ttc cag ccc gaa ccc caa atc ggg gag 19710
Ile Tyr Ala Asp Pro Thr Phe Gln Pro Glu Pro Gln Ile Gly Glu
3365 3370 3375
tca cag tgg aat gag gca gat gct aca gtc gcc ggc ggt aga gtg 19755
Ser Gln Trp Asn Glu Ala Asp Ala Thr Val Ala Gly Gly Arg Val
3380 3385 3390
cta aag aaa tct act ccc atg aaa cca tgc tat ggt tcc tat gca 19800
Leu Lys Lys Ser Thr Pro Met Lys Pro Cys Tyr Gly Ser Tyr Ala
3395 3400 3405
aga ccc aca aat gct aat gga ggt cag ggt gta cta acg gca aat 19845
Arg Pro Thr Asn Ala Asn Gly Gly Gln Gly Val Leu Thr Ala Asn
3410 3415 3420
gcc cag gga cag cta gaa tct cag gtt gaa atg caa ttc ttt tca 19890
Ala Gln Gly Gln Leu Glu Ser Gln Val Glu Met Gln Phe Phe Ser
3425 3430 3435
act tct gaa aac gcc cgt aac gag act aac aac att cag ccc aaa 19935
Thr Ser Glu Asn Ala Arg Asn Glu Thr Asn Asn Ile Gln Pro Lys
3440 3445 3450
ttg gtg ctg tat agt gag gat gtg cac atg gag acc ccg gat acg 19980
Leu Val Leu Tyr Ser Glu Asp Val His Met Glu Thr Pro Asp Thr
3455 3460 3465
cac ctt tct tac aag ccc gca aaa agc gat gac aat tca aaa atc 20025
His Leu Ser Tyr Lys Pro Ala Lys Ser Asp Asp Asn Ser Lys Ile
3470 3475 3480
atg ctg ggt cag cag tcc atg ccc aac aga cct aat tac atc ggc 20070
Met Leu Gly Gln Gln Ser Met Pro Asn Arg Pro Asn Tyr Ile Gly
3485 3490 3495
ttc aga gat aac ttt atc ggc ctc atg tat tac aat agc act ggc 20115
Phe Arg Asp Asn Phe Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly
3500 3505 3510
aac atg gga gtg ctt gca ggt cag gcc tct cag ttg aat gca gtg 20160
Asn Met Gly Val Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala Val
3515 3520 3525
gtg gac ttg caa gac aga aac aca gaa ctg tcc tac cag ctc ttg 20205
Val Asp Leu Gln Asp Arg Asn Thr Glu Leu Ser Tyr Gln Leu Leu
3530 3535 3540
ctt gat tcc atg ggt gac aga acc aga tac ttt tcc atg tgg aat 20250
Leu Asp Ser Met Gly Asp Arg Thr Arg Tyr Phe Ser Met Trp Asn
3545 3550 3555
cag gca gtg gac agt tat gac cca gat gtt aga att att gaa aat 20295
Gln Ala Val Asp Ser Tyr Asp Pro Asp Val Arg Ile Ile Glu Asn
3560 3565 3570
cat gga act gaa gac gag ctc ccc aac tat tgt ttc cct ctg ggt 20340
His Gly Thr Glu Asp Glu Leu Pro Asn Tyr Cys Phe Pro Leu Gly
3575 3580 3585
ggc ata ggg gta act gac act tac cag gct gtt aaa acc aac aat 20385
Gly Ile Gly Val Thr Asp Thr Tyr Gln Ala Val Lys Thr Asn Asn
3590 3595 3600
ggc aat aac ggg ggc cag gtg act tgg aca aaa gat gaa act ttt 20430
Gly Asn Asn Gly Gly Gln Val Thr Trp Thr Lys Asp Glu Thr Phe
3605 3610 3615
gca gat cgc aat gaa ata ggg gtg gga aac aat ttc gct atg gag 20475
Ala Asp Arg Asn Glu Ile Gly Val Gly Asn Asn Phe Ala Met Glu
3620 3625 3630
ata aac ctc agt gcc aac ctg tgg aga aac ttc ctg tac tcc aac 20520
Ile Asn Leu Ser Ala Asn Leu Trp Arg Asn Phe Leu Tyr Ser Asn
3635 3640 3645
gtg gcg ctg tac cta cca gac aag ctt aag tac aac ccc tcc aat 20565
Val Ala Leu Tyr Leu Pro Asp Lys Leu Lys Tyr Asn Pro Ser Asn
3650 3655 3660
gtg gac atc tct gac aac ccc aac acc tac gat tac atg aac aag 20610
Val Asp Ile Ser Asp Asn Pro Asn Thr Tyr Asp Tyr Met Asn Lys
3665 3670 3675
cga gtg gtg gcc ccg ggg ctg gtg gac tgc tac atc aac ctg ggc 20655
Arg Val Val Ala Pro Gly Leu Val Asp Cys Tyr Ile Asn Leu Gly
3680 3685 3690
gcg cgc tgg tcg ctg gac tac atg gac aac gtc aac ccc ttc aac 20700
Ala Arg Trp Ser Leu Asp Tyr Met Asp Asn Val Asn Pro Phe Asn
3695 3700 3705
cac cac cgc aat gcg ggc ctg cgc tac cgc tcc atg ctc ctg ggc 20745
His His Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly
3710 3715 3720
aac ggg cgc tac gtg ccc ttc cac atc cag gtg ccc cag aag ttc 20790
Asn Gly Arg Tyr Val Pro Phe His Ile Gln Val Pro Gln Lys Phe
3725 3730 3735
ttt gcc atc aag aac ctc ctc ctc ctg ccg ggc tcc tac acc tac 20835
Phe Ala Ile Lys Asn Leu Leu Leu Leu Pro Gly Ser Tyr Thr Tyr
3740 3745 3750
gag tgg aac ttc agg aag gat gtc aac atg gtc ctc cag agc tct 20880
Glu Trp Asn Phe Arg Lys Asp Val Asn Met Val Leu Gln Ser Ser
3755 3760 3765
ctg ggt aac gat ctc agg gtg gac ggg gcc agc atc aag ttc gag 20925
Leu Gly Asn Asp Leu Arg Val Asp Gly Ala Ser Ile Lys Phe Glu
3770 3775 3780
agc atc tgc ctc tac gcc acc ttc ttc ccc atg gcc cac aac acg 20970
Ser Ile Cys Leu Tyr Ala Thr Phe Phe Pro Met Ala His Asn Thr
3785 3790 3795
gcc tcc acg ctc gag gcc atg ctc agg aac gac acc aac gac cag 21015
Ala Ser Thr Leu Glu Ala Met Leu Arg Asn Asp Thr Asn Asp Gln
3800 3805 3810
tcc ttc aat gac tac ctc tcc gcc gcc aac atg ctc tac ccc ata 21060
Ser Phe Asn Asp Tyr Leu Ser Ala Ala Asn Met Leu Tyr Pro Ile
3815 3820 3825
ccc gcc aac gcc acc aac gtc ccc atc tcc atc ccc tcg cgc aac 21105
Pro Ala Asn Ala Thr Asn Val Pro Ile Ser Ile Pro Ser Arg Asn
3830 3835 3840
tgg gcg gcc ttc cgc ggc tgg gcc ttc acc cgc ctc aag acc aag 21150
Trp Ala Ala Phe Arg Gly Trp Ala Phe Thr Arg Leu Lys Thr Lys
3845 3850 3855
gag acc ccc tcc ctg ggc tcg gga ttc gac ccc tac tac acc tac 21195
Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr Tyr Thr Tyr
3860 3865 3870
tcg ggc tcc att ccc tac ctg gac ggc acc ttc tac ctc aac cac 21240
Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu Asn His
3875 3880 3885
act ttc aag aag gtc tcg gtc acc ttc gac tcc tcg gtc agc tgg 21285
Thr Phe Lys Lys Val Ser Val Thr Phe Asp Ser Ser Val Ser Trp
3890 3895 3900
ccg ggc aac gac cgt ctg ctc acc ccc aac gag ttc gag atc aag 21330
Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys
3905 3910 3915
cgc tcg gtc gac ggg gag ggc tac aac gtg gcc cag tgc aac atg 21375
Arg Ser Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met
3920 3925 3930
acc aag gac tgg ttc ctg gtc cag atg ctg gcc aac tac aac atc 21420
Thr Lys Asp Trp Phe Leu Val Gln Met Leu Ala Asn Tyr Asn Ile
3935 3940 3945
ggc tac cag ggc ttc tac atc cca gag agc tac aag gac agg atg 21465
Gly Tyr Gln Gly Phe Tyr Ile Pro Glu Ser Tyr Lys Asp Arg Met
3950 3955 3960
tac tcc ttc ttc agg aac ttc cag ccc atg agc cgg cag gtg gtg 21510
Tyr Ser Phe Phe Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val
3965 3970 3975
gac cag acc aag tac aag gac tac cag gag gtg ggc atc atc cac 21555
Asp Gln Thr Lys Tyr Lys Asp Tyr Gln Glu Val Gly Ile Ile His
3980 3985 3990
cag cac aac aac tcg ggc ttc gtg ggc tac ctc gcc ccc acc atg 21600
Gln His Asn Asn Ser Gly Phe Val Gly Tyr Leu Ala Pro Thr Met
3995 4000 4005
cgc gag gga cag gcc tac ccc gcc aac ttc ccc tat ccg ctc ata 21645
Arg Glu Gly Gln Ala Tyr Pro Ala Asn Phe Pro Tyr Pro Leu Ile
4010 4015 4020
ggc aag acc gcg gtc gac agc atc acc cag aaa aag ttc ctc tgc 21690
Gly Lys Thr Ala Val Asp Ser Ile Thr Gln Lys Lys Phe Leu Cys
4025 4030 4035
gac cgc acc ctc tgg cgc atc ccc ttc tcc agc aac ttc atg tcc 21735
Asp Arg Thr Leu Trp Arg Ile Pro Phe Ser Ser Asn Phe Met Ser
4040 4045 4050
atg ggt gcg ctc tcg gac ctg ggc cag aac ttg ctc tac gcc aac 21780
Met Gly Ala Leu Ser Asp Leu Gly Gln Asn Leu Leu Tyr Ala Asn
4055 4060 4065
tcc gcc cac gcc ctc gac atg acc ttc gag gtc gac ccc atg gac 21825
Ser Ala His Ala Leu Asp Met Thr Phe Glu Val Asp Pro Met Asp
4070 4075 4080
gag ccc acc ctt ctc tat gtt ctg ttc gaa gtc ttt gac gtg gtc 21870
Glu Pro Thr Leu Leu Tyr Val Leu Phe Glu Val Phe Asp Val Val
4085 4090 4095
cgg gtc cac cag ccg cac cgc ggc gtc atc gag acc gtg tac ctg 21915
Arg Val His Gln Pro His Arg Gly Val Ile Glu Thr Val Tyr Leu
4100 4105 4110
cgt acg ccc ttc tcg gcc ggc aac gcc acc acc taaagaagca 21958
Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr
4115 4120
agccgcagtc atcgccgcct gc atg ccg tcg ggt tcc acc gag caa gag 22007
Met Pro Ser Gly Ser Thr Glu Gln Glu
4125 4130
ctc agg gcc atc gtc aga gac ctg gga tgc ggg ccc tat ttt ttg 22052
Leu Arg Ala Ile Val Arg Asp Leu Gly Cys Gly Pro Tyr Phe Leu
4135 4140 4145
ggc acc ttc gac aag cgc ttc cct ggc ttt gtc tcc cca cac aag 22097
Gly Thr Phe Asp Lys Arg Phe Pro Gly Phe Val Ser Pro His Lys
4150 4155 4160
ctg gcc tgc gcc atc gtc aac acg gcc ggc cgc gag acc ggg ggc 22142
Leu Ala Cys Ala Ile Val Asn Thr Ala Gly Arg Glu Thr Gly Gly
4165 4170 4175
gtg cac tgg ctg gcc ttc gcc tgg aac ccg cgc tcc aaa aca tgc 22187
Val His Trp Leu Ala Phe Ala Trp Asn Pro Arg Ser Lys Thr Cys
4180 4185 4190
ttc ctc ttt gac ccc ttc ggc ttt tcg gac cag cgg ctc aag caa 22232
Phe Leu Phe Asp Pro Phe Gly Phe Ser Asp Gln Arg Leu Lys Gln
4195 4200 4205
atc tac gag ttc gag tac gag ggc ttg ctg cgt cgc agc gcc atc 22277
Ile Tyr Glu Phe Glu Tyr Glu Gly Leu Leu Arg Arg Ser Ala Ile
4210 4215 4220
gcc tcc tcg ccc gac cgc tgc gtc acc ctc gaa aag tcc acc cag 22322
Ala Ser Ser Pro Asp Arg Cys Val Thr Leu Glu Lys Ser Thr Gln
4225 4230 4235
acc gtg cag ggg ccc gac tcg gcc gcc tgc ggt ctc ttc tgc tgc 22367
Thr Val Gln Gly Pro Asp Ser Ala Ala Cys Gly Leu Phe Cys Cys
4240 4245 4250
atg ttt ctg cac gcc ttt gtg cac tgg cct cag agt ccc atg gac 22412
Met Phe Leu His Ala Phe Val His Trp Pro Gln Ser Pro Met Asp
4255 4260 4265
cgc aac ccc acc atg aac ttg ctg acg ggg gtg ccc aac tcc atg 22457
Arg Asn Pro Thr Met Asn Leu Leu Thr Gly Val Pro Asn Ser Met
4270 4275 4280
ctc cag agc ccc cag gtc gag ccc acc ctg cgc cgc aac cag gag 22502
Leu Gln Ser Pro Gln Val Glu Pro Thr Leu Arg Arg Asn Gln Glu
4285 4290 4295
cag ctc tac agc ttc ctg gag cgc cac tcg ccc tac ttc cgc cgc 22547
Gln Leu Tyr Ser Phe Leu Glu Arg His Ser Pro Tyr Phe Arg Arg
4300 4305 4310
cac agc gca cag atc agg agg gcc acc tcc ttc tgc cac ttg caa 22592
His Ser Ala Gln Ile Arg Arg Ala Thr Ser Phe Cys His Leu Gln
4315 4320 4325
gag atg caa gaa ggg taataacgat gtacacactt tttttctcaa taaatggcat 22647
Glu Met Gln Glu Gly
4330
ttttttattt atacaagctc tctggggtat tcatttccca ccaccaccac ccgccgttgt 22707
cgccatctgg ctctatttag aaatcgaaag ggttctgccg ggagtcgccg tgcgccacgg 22767
gcagggacac gttgcgatac tggtagcggg tgccccactt gaactcgggc accaccaggc 22827
gaggcagctc ggggaagttt tcgctccaca ggctgcgggt cagcaccagc gcgttcatca 22887
ggtcgggcgc cgagatcttg aagtcgcagt tggggccgcc gccctgcgcg cgcgagttgc 22947
ggtacaccgg gttgcagcac tggaacacca acagcgccgg gtgcttcacg ctggccagca 23007
cgctgcggtc ggagatgagc tcggcgtcca ggtcctccgc gttgctcagc gcgaacgggg 23067
tcatcttggg cacttgccgc cccaggaagg gcgcgtgccc cggtttcgag ttgcagtcgc 23127
agcgcagcgg gatcagcagg tgcccgtgcc cggactcggc gttggggtac agcgcgcgca 23187
tgaaggcctg catctggcgg aaggccatct gggccttggc gccctccgag aagaacatgc 23247
cacaggactt gcccgagaac tggtttgcgg ggcagctggc gtcgtgcagg cagcagcgcg 23307
cgtcggtgtt ggcgatctgc accacgttgc gcccccaccg gttcttcacg atcttggcct 23367
tggacgattg ctccttcagc gcgcgctgcc cgttctcgct ggtcacatcc atctcgatca 23427
catgttcctt gttcaccatg ctgctgccgt gcagacactt cagctcgccc tccgtctcgg 23487
tgcagcggtg ctgccacagc gcgcagcccg tgggctcgaa agacttgtag gtcacctccg 23547
cgaaggactg caggtacccc tgcaaaaagc ggcccatcat ggtcacgaag gtcttgttgc 23607
tgctgaaggt cagctgcagc ccgcggtgct cctcgttcag ccaggtcttg cacacggccg 23667
ccagcgcctc cacctggtcg ggcagcatct tgaagttcac cttcagctca ttctccacgt 23727
ggtacttgtc catcagcgtg cgcgccgcct ccatgccctt ctcccaggcc gacaccagcg 23787
gcaggctcac ggggttcttc accatcaccg tggccgccgc ctccgccgcg ctttcgcttt 23847
ccgccccgct gttctcttcc tcttcctcct cttcctcgcc gccgcccact cgcagccccc 23907
gcaccacggg gtcgtcttcc tgcaggcgct gtaccttgcg cttgccgttg cgcccctgct 23967
tgatgcgcac gggcgggttg ctgaagccca ccatcaccag cgcggcctct tcttgctcgt 24027
cctcgctgtc cagaatgacc tccggggagg gggggttggt catcctcagt accgaggcac 24087
gcttcttttt cttcctgggg gcgttcgcca gctccgcggc tgcggccgct gccgaggtcg 24147
aaggccgagg gctgggcgtg cgcggcacca gcgcgtcctg cgagccgtcc tcgtcctcct 24207
cggactcgag acggaggcgg gcccgcttct tcgggggcgc gcggggcggc ggaggcggcg 24267
gcggcgacgg agacggggac gagacatcgt ccagggtggg tggacggcgg gccgcgccgc 24327
gtccgcgctc gggggtggtc tcgcgctggt cctcttcccg actggccatc tcccactgct 24387
ccttctccta taggcagaaa gagatc atg gag tct ctc atg cga gtc gag 24437
Met Glu Ser Leu Met Arg Val Glu
4335 4340
aag gag gag gac agc cta acc gcc ccc tct gag ccc tcc acc acc 24482
Lys Glu Glu Asp Ser Leu Thr Ala Pro Ser Glu Pro Ser Thr Thr
4345 4350 4355
gcc gcc acc acc gcc aat gcc gcc gcg gac gac gcg ccc acc gag 24527
Ala Ala Thr Thr Ala Asn Ala Ala Ala Asp Asp Ala Pro Thr Glu
4360 4365 4370
acc acc gcc agt acc acc ctc ccc agc gac gca ccc ccg ctc gag 24572
Thr Thr Ala Ser Thr Thr Leu Pro Ser Asp Ala Pro Pro Leu Glu
4375 4380 4385
aat gaa gtg ctg atc gag cag gac ccg ggt ttt gtg agc gga gag 24617
Asn Glu Val Leu Ile Glu Gln Asp Pro Gly Phe Val Ser Gly Glu
4390 4395 4400
gag gat gag gtg gat gag aag gag aag gag gag gtc gcc gcc tca 24662
Glu Asp Glu Val Asp Glu Lys Glu Lys Glu Glu Val Ala Ala Ser
4405 4410 4415
gtg cca aaa gag gat aaa aag caa gac cag gac gac gca gat aag 24707
Val Pro Lys Glu Asp Lys Lys Gln Asp Gln Asp Asp Ala Asp Lys
4420 4425 4430
gat gag aca gca gtc ggg cgg ggg aac gga agc cat gat gct gat 24752
Asp Glu Thr Ala Val Gly Arg Gly Asn Gly Ser His Asp Ala Asp
4435 4440 4445
gac ggc tac cta gac gtg gga gac gac gtg ctg ctt aag cac ctg 24797
Asp Gly Tyr Leu Asp Val Gly Asp Asp Val Leu Leu Lys His Leu
4450 4455 4460
cac cgc cag tgc gtc atc gtc tgc gac gcg ctg cag gag cgc tgc 24842
His Arg Gln Cys Val Ile Val Cys Asp Ala Leu Gln Glu Arg Cys
4465 4470 4475
gaa gtg ccc ctg gac gtg gcg gag gtc agc cgc gcc tac gag cgg 24887
Glu Val Pro Leu Asp Val Ala Glu Val Ser Arg Ala Tyr Glu Arg
4480 4485 4490
cac ctc ttc gcg ccg cac gtg ccc ccc aag cgc cgg gag aac ggc 24932
His Leu Phe Ala Pro His Val Pro Pro Lys Arg Arg Glu Asn Gly
4495 4500 4505
acc tgc gag ccc aac ccg cgt ctc aac ttc tac ccg gtc ttc gcg 24977
Thr Cys Glu Pro Asn Pro Arg Leu Asn Phe Tyr Pro Val Phe Ala
4510 4515 4520
gta ccc gag gtg ctg gcc acc tac cac atc ttt ttc caa aac tgc 25022
Val Pro Glu Val Leu Ala Thr Tyr His Ile Phe Phe Gln Asn Cys
4525 4530 4535
aag atc ccc ctc tcc tgc cgc gct aac cgc acc cgc gcc gac aaa 25067
Lys Ile Pro Leu Ser Cys Arg Ala Asn Arg Thr Arg Ala Asp Lys
4540 4545 4550
acc ctg acc ctg cgg cag ggc gcc cac ata cct gat att gcc tct 25112
Thr Leu Thr Leu Arg Gln Gly Ala His Ile Pro Asp Ile Ala Ser
4555 4560 4565
ctg gag gaa gtg ccc aag atc ttc gag ggt ctc ggt cgc gac gag 25157
Leu Glu Glu Val Pro Lys Ile Phe Glu Gly Leu Gly Arg Asp Glu
4570 4575 4580
aaa cgg gcg gcg aac gct ctg cac gga gac agc gaa aac gag agt 25202
Lys Arg Ala Ala Asn Ala Leu His Gly Asp Ser Glu Asn Glu Ser
4585 4590 4595
cac tcg ggg gtg ctg gtg gag ctc gag ggc gac aac gcg cgc ctg 25247
His Ser Gly Val Leu Val Glu Leu Glu Gly Asp Asn Ala Arg Leu
4600 4605 4610
gcc gta ctc aag cgc agc ata gag gtc acc cac ttt gcc tac ccg 25292
Ala Val Leu Lys Arg Ser Ile Glu Val Thr His Phe Ala Tyr Pro
4615 4620 4625
gcg ctc aac ctg ccc ccc aag gtc atg agt gtg gtc atg ggc gag 25337
Ala Leu Asn Leu Pro Pro Lys Val Met Ser Val Val Met Gly Glu
4630 4635 4640
ctc atc atg cgc cgc gcc cag ccc ctg gcc gcg gat gca aac ttg 25382
Leu Ile Met Arg Arg Ala Gln Pro Leu Ala Ala Asp Ala Asn Leu
4645 4650 4655
caa gag tcc tca gag gaa ggc ctg ccc gcg gtc agc gac gag cag 25427
Gln Glu Ser Ser Glu Glu Gly Leu Pro Ala Val Ser Asp Glu Gln
4660 4665 4670
ctg gcg cgc tgg ctg gaa acc cgc gac ccc gcg cag ctg gag gag 25472
Leu Ala Arg Trp Leu Glu Thr Arg Asp Pro Ala Gln Leu Glu Glu
4675 4680 4685
cgg cgc aag ctc atg atg gcc gcg gtg ctg gtc acc gtg gag ctc 25517
Arg Arg Lys Leu Met Met Ala Ala Val Leu Val Thr Val Glu Leu
4690 4695 4700
gag tgt ctg cag cgc ttc ttc gcg gac ccc gag atg cag cgc aag 25562
Glu Cys Leu Gln Arg Phe Phe Ala Asp Pro Glu Met Gln Arg Lys
4705 4710 4715
ctc gag gag acc ctg cac tac acc ttc cgc cag ggc tac gtg cgc 25607
Leu Glu Glu Thr Leu His Tyr Thr Phe Arg Gln Gly Tyr Val Arg
4720 4725 4730
cag gcc tgc aag atc tcc aac gtg gag ctc tgc aac ctg gtc tcc 25652
Gln Ala Cys Lys Ile Ser Asn Val Glu Leu Cys Asn Leu Val Ser
4735 4740 4745
tac ctg ggc atc ctg cac gag aac cgc ctc ggg cag aac gtc ctg 25697
Tyr Leu Gly Ile Leu His Glu Asn Arg Leu Gly Gln Asn Val Leu
4750 4755 4760
cac tcc acc ctc aaa ggg gag gcg cgc cgc gac tac atc cgc gac 25742
His Ser Thr Leu Lys Gly Glu Ala Arg Arg Asp Tyr Ile Arg Asp
4765 4770 4775
tgc gcc tac ctc ttc ctc tgc tac acc tgg cag acg gcc atg ggg 25787
Cys Ala Tyr Leu Phe Leu Cys Tyr Thr Trp Gln Thr Ala Met Gly
4780 4785 4790
gtc tgg cag cag tgc ctg gag gag cgc aac ctc aag gag ctg gaa 25832
Val Trp Gln Gln Cys Leu Glu Glu Arg Asn Leu Lys Glu Leu Glu
4795 4800 4805
aag ctc ctc aag cgc acc ctc agg gac ctc tgg acg ggc ttc aac 25877
Lys Leu Leu Lys Arg Thr Leu Arg Asp Leu Trp Thr Gly Phe Asn
4810 4815 4820
gag cgc tcg gtg gcc gcc gcg ctg gcg gac atc atc ttc ccc gag 25922
Glu Arg Ser Val Ala Ala Ala Leu Ala Asp Ile Ile Phe Pro Glu
4825 4830 4835
cgc ttg ctc aag acc ctg cag cag ggc ctg cca gac ttc acc agc 25967
Arg Leu Leu Lys Thr Leu Gln Gln Gly Leu Pro Asp Phe Thr Ser
4840 4845 4850
cag agc atg ctg cag aac ttc agg act ttc atc ctg gag cgc tcg 26012
Gln Ser Met Leu Gln Asn Phe Arg Thr Phe Ile Leu Glu Arg Ser
4855 4860 4865
ggc atc ctg ccg gcc act tgc tgc gcg ctg ccc agc gac ttc gtg 26057
Gly Ile Leu Pro Ala Thr Cys Cys Ala Leu Pro Ser Asp Phe Val
4870 4875 4880
ccc atc aag tac agg gag tgc ccg ccg ccg ctc tgg ggc cac tgc 26102
Pro Ile Lys Tyr Arg Glu Cys Pro Pro Pro Leu Trp Gly His Cys
4885 4890 4895
tac ctc ttc cag ctg gcc aac tac ctc gcc tac cac tcg gac ctc 26147
Tyr Leu Phe Gln Leu Ala Asn Tyr Leu Ala Tyr His Ser Asp Leu
4900 4905 4910
atg gaa gac gtg agc ggc gag ggc ctg ctc gag tgc cac tgc cgc 26192
Met Glu Asp Val Ser Gly Glu Gly Leu Leu Glu Cys His Cys Arg
4915 4920 4925
tgc aac ctc tgc acg ccc cac cgc tct cta gtc tgc aac ccg cag 26237
Cys Asn Leu Cys Thr Pro His Arg Ser Leu Val Cys Asn Pro Gln
4930 4935 4940
ctg ctc agc gag agt cag att atc ggt acc ttc gag ctg cag ggt 26282
Leu Leu Ser Glu Ser Gln Ile Ile Gly Thr Phe Glu Leu Gln Gly
4945 4950 4955
ccc tcg cct gac gag aag tcc gcg gct ccg ggg ctg aaa ctc act 26327
Pro Ser Pro Asp Glu Lys Ser Ala Ala Pro Gly Leu Lys Leu Thr
4960 4965 4970
ccg ggg cta tgg act tcc gcc tac cta cgc aaa ttt gta cct gag 26372
Pro Gly Leu Trp Thr Ser Ala Tyr Leu Arg Lys Phe Val Pro Glu
4975 4980 4985
gac tac cac gcc cac gag atc agg ttc tac gaa gac caa tcc cgc 26417
Asp Tyr His Ala His Glu Ile Arg Phe Tyr Glu Asp Gln Ser Arg
4990 4995 5000
ccg ccc aag gcg gag ctc acc gcc tgc gtc atc acc cag ggg cac 26462
Pro Pro Lys Ala Glu Leu Thr Ala Cys Val Ile Thr Gln Gly His
5005 5010 5015
atc ctg ggc caa ttg caa gcc atc aac aaa gcc cgc cga gag ttc 26507
Ile Leu Gly Gln Leu Gln Ala Ile Asn Lys Ala Arg Arg Glu Phe
5020 5025 5030
ttg ctg aaa aag ggt cgg ggg gtg tac ctg gac ccc cag tcc ggc 26552
Leu Leu Lys Lys Gly Arg Gly Val Tyr Leu Asp Pro Gln Ser Gly
5035 5040 5045
gag gag cta aac ccg cta ccc ccg ccg ccg ccc cag cag cgg gac 26597
Glu Glu Leu Asn Pro Leu Pro Pro Pro Pro Pro Gln Gln Arg Asp
5050 5055 5060
ctt gct tcc cag gat ggc acc cag aaa gaa gca gca gcc gcc gcc 26642
Leu Ala Ser Gln Asp Gly Thr Gln Lys Glu Ala Ala Ala Ala Ala
5065 5070 5075
gca gcc ata cat gct tct gga gga aga gga gga gga ctg gga cag 26687
Ala Ala Ile His Ala Ser Gly Gly Arg Gly Gly Gly Leu Gly Gln
5080 5085 5090
tca ggc aga gga ggt ttc gga cga gga gca gga gga gat gat gga 26732
Ser Gly Arg Gly Gly Phe Gly Arg Gly Ala Gly Gly Asp Asp Gly
5095 5100 5105
aga ctg gga gga gga cag cag cct aga cga gga agc ttc aga ggc 26777
Arg Leu Gly Gly Gly Gln Gln Pro Arg Arg Gly Ser Phe Arg Gly
5110 5115 5120
cga aga ggt ggc aga cgc aac acc atc acc ctc ggt cgc agc ccc 26822
Arg Arg Gly Gly Arg Arg Asn Thr Ile Thr Leu Gly Arg Ser Pro
5125 5130 5135
ctc gcc ggg gcc cct gaa atc ctc cga acc cag cac cag cgc tat 26867
Leu Ala Gly Ala Pro Glu Ile Leu Arg Thr Gln His Gln Arg Tyr
5140 5145 5150
aac ctc cgc tcc tcc ggc gcc ggc gcc acc cgc ccg cag acc caa 26912
Asn Leu Arg Ser Ser Gly Ala Gly Ala Thr Arg Pro Gln Thr Gln
5155 5160 5165
ccg tagatgggac accacaggaa ccggggtcgg taagtccaag tgcccgccgc 26965
Pro
cgccaccgca gcagcagcag cagcagcgcc agggctaccg ctcgtggcgc gggcacaaga 27025
acgccatagt cgcctgcttg caagactgcg ggggcaacat ctctttcgcc cgccgcttcc 27085
tgctattcca ccacggggtc gcctttcccc gcaatgtcct gcattactac cgtcatctct 27145
acagccccta ctgcagcggc gacccagagg cggcagcggc agccacagcg gcgaccacca 27205
cctaggaaga tatcctccgc gggcaagaca gcggcagcag cggccaggag acccgcggcg 27265
gcagcggcgg gagcggtggg cgctctgcgc ctctcgccca acgaacccct ctcgacccgg 27325
gagctcagac acaggatctt ccccactttg tatgccatct tccaacagag cagaggccag 27385
gagcaggagc tgaaaataaa aaacagatct ctgcgctccc tcacccgcag ctgtctgtat 27445
cacaaaagcg aagatcagct tcggcgcacg ctggaggacg cggaggcact cttcagcaaa 27505
tactgcgcgc tcactcttaa agactagctc cgcgcccttc tcgaatttag gcgggagaaa 27565
actacgtcat cgccggccgc cgcccagccc gcccagccga g atg agc aaa gag 27618
Met Ser Lys Glu
5170
att ccc acg cca tac atg tgg agc tac cag ccg cag atg gga ctc 27663
Ile Pro Thr Pro Tyr Met Trp Ser Tyr Gln Pro Gln Met Gly Leu
5175 5180 5185
gcg gcg gga gcg gcc cag gac tac tcc acc cgc atg aac tac atg 27708
Ala Ala Gly Ala Ala Gln Asp Tyr Ser Thr Arg Met Asn Tyr Met
5190 5195 5200
agc gcg gga ccc cac atg atc tca cag gtc aac ggg atc cgc gcc 27753
Ser Ala Gly Pro His Met Ile Ser Gln Val Asn Gly Ile Arg Ala
5205 5210 5215
cag cga aac caa ata ctg ctg gaa cag gcg gcc atc acc gcc acg 27798
Gln Arg Asn Gln Ile Leu Leu Glu Gln Ala Ala Ile Thr Ala Thr
5220 5225 5230
ccc cgc cat aat ctc aac ccc cga aat tgg ccc gcc gcc ctc gtg 27843
Pro Arg His Asn Leu Asn Pro Arg Asn Trp Pro Ala Ala Leu Val
5235 5240 5245
tac cag gaa acc ccc tcc gcc acc acc gta cta ctt ccg cgt gac 27888
Tyr Gln Glu Thr Pro Ser Ala Thr Thr Val Leu Leu Pro Arg Asp
5250 5255 5260
gcc cag gcc gaa gtc cag atg act aac tca ggg gcg cag ctc gcg 27933
Ala Gln Ala Glu Val Gln Met Thr Asn Ser Gly Ala Gln Leu Ala
5265 5270 5275
ggc ggc ttt cgt cac ggg gcg cgg ccg ctc cga cca ggt ata aga 27978
Gly Gly Phe Arg His Gly Ala Arg Pro Leu Arg Pro Gly Ile Arg
5280 5285 5290
cac ctg atg atc aga ggc cga ggt atc cag ctc aac gac gag tcg 28023
His Leu Met Ile Arg Gly Arg Gly Ile Gln Leu Asn Asp Glu Ser
5295 5300 5305
gtg agc tct tcg ctc ggt ctc cgt ccg gac gga act ttc cag ctc 28068
Val Ser Ser Ser Leu Gly Leu Arg Pro Asp Gly Thr Phe Gln Leu
5310 5315 5320
gcc gga tcc ggc cgc tct tcg ttc acg ccc cgc cag gcg tac ctt 28113
Ala Gly Ser Gly Arg Ser Ser Phe Thr Pro Arg Gln Ala Tyr Leu
5325 5330 5335
act ctg cag acc tcg tcc tcg gag ccc cgc tcc ggc ggc atc gga 28158
Thr Leu Gln Thr Ser Ser Ser Glu Pro Arg Ser Gly Gly Ile Gly
5340 5345 5350
acc ctc cag ttc gtg gag gag ttc gtg ccc tcg gtc tac ttc aac 28203
Thr Leu Gln Phe Val Glu Glu Phe Val Pro Ser Val Tyr Phe Asn
5355 5360 5365
ccc ttc tcg gga cct ccc gga cgc tac ccc gac cag ttc att ccg 28248
Pro Phe Ser Gly Pro Pro Gly Arg Tyr Pro Asp Gln Phe Ile Pro
5370 5375 5380
aac ttt gac gcg gtg aag gac tcg gcg gac ggc tac gac tga atg 28293
Asn Phe Asp Ala Val Lys Asp Ser Ala Asp Gly Tyr Asp Met
5385 5390 5395
tca ggt gcc gag gca gag cag ctt cgc ctg aga cac ctc gag cac 28338
Ser Gly Ala Glu Ala Glu Gln Leu Arg Leu Arg His Leu Glu His
5400 5405 5410
tgc cgc cgc cac aag tgc ttc gcc cgc ggt tcc ggt gag ttc tgc 28383
Cys Arg Arg His Lys Cys Phe Ala Arg Gly Ser Gly Glu Phe Cys
5415 5420 5425
tac ttt cag cta ccc gag gag cat acc gag ggg ccg gcg cac ggc 28428
Tyr Phe Gln Leu Pro Glu Glu His Thr Glu Gly Pro Ala His Gly
5430 5435 5440
gtc cgc ctg acc acc cag ggc gag gtt acc tgt tcc ctc atc cgg 28473
Val Arg Leu Thr Thr Gln Gly Glu Val Thr Cys Ser Leu Ile Arg
5445 5450 5455
gag ttc acc ctc cgt ccc ctg cta gtg gag cgg gag cgg ggt ccc 28518
Glu Phe Thr Leu Arg Pro Leu Leu Val Glu Arg Glu Arg Gly Pro
5460 5465 5470
tgt gtc cta act atc gcc tgc aac tgc cct aac cct gga tta cat 28563
Cys Val Leu Thr Ile Ala Cys Asn Cys Pro Asn Pro Gly Leu His
5475 5480 5485
caa gat ctt tgc tgt cat ctc tgt gct gag ttt aat aaa cgc 28605
Gln Asp Leu Cys Cys His Leu Cys Ala Glu Phe Asn Lys Arg
5490 5495
tgagatcaga atctactggg gctcctgtcg ccatcctgtg aacgccaccg tcttcaccca 28665
ccccgaccag gcccaggcga acctcacctg cggtctgcat cggagggcca agaagtacct 28725
cacctggtac ttcaacggca ccccctttgt ggtttacaac agcttcgacg gggacggagt 28785
ctccctgaaa gaccagctct ccggtctcag ctactccatc cacaagaaca ccaccctcca 28845
actcttccct ccctacctgc cgggaaccta cgagtgcgtc accggccgct gcacccacct 28905
cacccgcctg atcgtaaacc agagctttcc gggaacagat aactctctct tccccagaac 28965
aggaggtgag ctcaggaaac tccccgggga ccagggcgga gacgtacctt cgacccttgt 29025
ggggttagga ttttttatta ccgggttgct ggctctttta atcaaagctt ccttgagatt 29085
tgttctttcc ttctacgtgt atgaacacct caacctccaa taactctacc ctttcttcgg 29145
aatcaggtga cttctctgaa atcgggcttg gtgtgctgct tactctgttg atttttttcc 29205
ttatcatact cagccttctg tgcctcaggc tcgccgcctg ctgcgcacac atctatatct 29265
actgctggtt gctcaagtgc aggggtcgcc acccaag atg aac agg tac atg 29317
Met Asn Arg Tyr Met
5500
gtc cta tcg atc cta ggc ctg ctg gcc ctg gcg gcc tgc agc gcc 29362
Val Leu Ser Ile Leu Gly Leu Leu Ala Leu Ala Ala Cys Ser Ala
5505 5510 5515
gcc aaa aaa gag att acc ttt gag gag ccc gct tgc aat gta act 29407
Ala Lys Lys Glu Ile Thr Phe Glu Glu Pro Ala Cys Asn Val Thr
5520 5525 5530
ttc aag ccc gag ggt gac caa tgc acc acc ctc gtc aaa tgc gtt 29452
Phe Lys Pro Glu Gly Asp Gln Cys Thr Thr Leu Val Lys Cys Val
5535 5540 5545
acc aat cat gag agg ctg cgc atc gac tac aaa aac aaa act ggc 29497
Thr Asn His Glu Arg Leu Arg Ile Asp Tyr Lys Asn Lys Thr Gly
5550 5555 5560
cgg ttt gcg gtc tat agt gtg ttt acg ccc gga gac ccc tct aac 29542
Arg Phe Ala Val Tyr Ser Val Phe Thr Pro Gly Asp Pro Ser Asn
5565 5570 5575
tac tct gtc acc gtc ttc cag ggc gga cag tct aag ata ttc aat 29587
Tyr Ser Val Thr Val Phe Gln Gly Gly Gln Ser Lys Ile Phe Asn
5580 5585 5590
tac act ttc cct ttt tat gag ttg tgc gat gcg gtc atg tac atg 29632
Tyr Thr Phe Pro Phe Tyr Glu Leu Cys Asp Ala Val Met Tyr Met
5595 5600 5605
tca aaa cag tac aac ctg tgg cct ccc tct ccc cag gcg tgt gtg 29677
Ser Lys Gln Tyr Asn Leu Trp Pro Pro Ser Pro Gln Ala Cys Val
5610 5615 5620
gaa aat act ggg tct tac tgc tgt atg gct ttc gca atc act acg 29722
Glu Asn Thr Gly Ser Tyr Cys Cys Met Ala Phe Ala Ile Thr Thr
5625 5630 5635
ctc gct cta atc tgc acg gtg cta tat ata aaa ttc agg cag agg 29767
Leu Ala Leu Ile Cys Thr Val Leu Tyr Ile Lys Phe Arg Gln Arg
5640 5645 5650
cga atc ttt atc gat gaa aag aaa atg cct tgatcgctaa caccggcttt 29817
Arg Ile Phe Ile Asp Glu Lys Lys Met Pro
5655 5660
ctatctgcag a atg aat gca atc acc tcc cta cta atc acc acc acc 29864
Met Asn Ala Ile Thr Ser Leu Leu Ile Thr Thr Thr
5665 5670 5675
ctc ctt gcg att gcc cat ggg ttg aca cga atc gaa gtg cca gtg 29909
Leu Leu Ala Ile Ala His Gly Leu Thr Arg Ile Glu Val Pro Val
5680 5685 5690
ggg tcc aat gtc acc atg gtg ggc ccc gcc ggc aat tcc acc ctc 29954
Gly Ser Asn Val Thr Met Val Gly Pro Ala Gly Asn Ser Thr Leu
5695 5700 5705
atg tgg gaa aaa ttt gtc cgc aat caa tgg gtt cat ttc tgc tct 29999
Met Trp Glu Lys Phe Val Arg Asn Gln Trp Val His Phe Cys Ser
5710 5715 5720
aac cga atc agt atc aag ccc aga gcc atc tgc gat ggg caa aat 30044
Asn Arg Ile Ser Ile Lys Pro Arg Ala Ile Cys Asp Gly Gln Asn
5725 5730 5735
cta act ctg atc aat gtg caa atg atg gat gct ggg tac tat tac 30089
Leu Thr Leu Ile Asn Val Gln Met Met Asp Ala Gly Tyr Tyr Tyr
5740 5745 5750
ggg cag cgg gga gaa atc att aat tac tgg cga ccc cac aag gac 30134
Gly Gln Arg Gly Glu Ile Ile Asn Tyr Trp Arg Pro His Lys Asp
5755 5760 5765
tac atg ctg cat gta gtc gag gca ctt ccc act acc acc ccc act 30179
Tyr Met Leu His Val Val Glu Ala Leu Pro Thr Thr Thr Pro Thr
5770 5775 5780
acc acc tct ccc acc acc act acc acc acc act act act act act 30224
Thr Thr Ser Pro Thr Thr Thr Thr Thr Thr Thr Thr Thr Thr Thr
5785 5790 5795
act acc act acc gct gcc cgc cat acc cgc aaa agc acc atg att 30269
Thr Thr Thr Thr Ala Ala Arg His Thr Arg Lys Ser Thr Met Ile
5800 5805 5810
agc aca aag ccc cct cgt gct cac tcc cac gcc ggc ggg ccc atc 30314
Ser Thr Lys Pro Pro Arg Ala His Ser His Ala Gly Gly Pro Ile
5815 5820 5825
ggt gcg acc tca gaa acc acc gag ctt tgc ttc tgc caa tgc act 30359
Gly Ala Thr Ser Glu Thr Thr Glu Leu Cys Phe Cys Gln Cys Thr
5830 5835 5840
aac gcc agc gct cat gaa ctg ttc gac ctg gag aat gag gat gcc 30404
Asn Ala Ser Ala His Glu Leu Phe Asp Leu Glu Asn Glu Asp Ala
5845 5850 5855
cag cag agc tcc gct tgc ctg acc cag gag gct gtg gag ccc gtt 30449
Gln Gln Ser Ser Ala Cys Leu Thr Gln Glu Ala Val Glu Pro Val
5860 5865 5870
gcc ctg aag cag atc ggt gat tca ata att gac tct tct tct ttt 30494
Ala Leu Lys Gln Ile Gly Asp Ser Ile Ile Asp Ser Ser Ser Phe
5875 5880 5885
gcc act ccc gaa tac cct ccc gat tct act ttc cac atc acg ggt 30539
Ala Thr Pro Glu Tyr Pro Pro Asp Ser Thr Phe His Ile Thr Gly
5890 5895 5900
acc aaa gac cct aac ctc tct ttc tac ctg atg ctg ctg ctc tgt 30584
Thr Lys Asp Pro Asn Leu Ser Phe Tyr Leu Met Leu Leu Leu Cys
5905 5910 5915
atc tct gtg gtc tct tcc gcg ctg atg tta ctg ggg atg ttc tgc 30629
Ile Ser Val Val Ser Ser Ala Leu Met Leu Leu Gly Met Phe Cys
5920 5925 5930
tgc ctg atc tgc cgc aga aag aga aaa gct cgc tct cag ggc caa 30674
Cys Leu Ile Cys Arg Arg Lys Arg Lys Ala Arg Ser Gln Gly Gln
5935 5940 5945
cca ctg atg ccc ttc ccc tac ccc ccg gat ttt gca gat aac aag 30719
Pro Leu Met Pro Phe Pro Tyr Pro Pro Asp Phe Ala Asp Asn Lys
5950 5955 5960
ata tgagctcgct gctgacacta accgctttac tagcctgcgc tctaaccctt 30772
Ile
gtcgcttgcg actcgagatt ccacaatgtc acagctgtgg caggagaaaa tgttactttc 30832
aactccacgg ccgataccca gtggtcgtgg agtggctcag gtagctactt aactatctgc 30892
aatagctcca cttcccccag catatcccca accaagtacc aatgcaatgc cagcctgttc 30952
accctcatca acgcttccac cctggacaat ggactctatg taggctatgt accctttggt 31012
gggcaaggaa agacccacgc ttacaacctg gaagttcgcc agcccagaac cactacccaa 31072
gcttctccca ccaccaccac caccatcagc agcagcagca gcagcagcca cagcagcagc 31132
agcagattat tgactttggt tttggccagc tcatctgccg ctacccaggc catctacagc 31192
tctgtgcccg aaaccactca gatccaccgc ccagaaacga ccaccgccac caccctacac 31252
acctccagcg atcagatgcc gaccaacatc acccccttgg ctcttcaaat gggacttaca 31312
agccccactc caaaaccagt ggatgcgacc gaggtctccg ccctcgtcaa tgactgggcg 31372
gggctgggaa tgtggtggtt cgccataggc atgatggcgc tctgcctgct tctgctctgg 31432
ctcatctgct gcctccaccg caggcgagcc agacccccca tctatagacc catcattgtc 31492
ctgaaccccg ataatgatgg gatccataga ttggatggcc tgaaaaacct acttttttct 31552
tttacagtat gataaattga gac atg cct cgc att ttc ttg tac atg ttc 31602
Met Pro Arg Ile Phe Leu Tyr Met Phe
5965 5970
ctt ctc cca cct ttt ctg ggg tgt tct acg ctg gcc gct gtg tct 31647
Leu Leu Pro Pro Phe Leu Gly Cys Ser Thr Leu Ala Ala Val Ser
5975 5980 5985
cac ctg gag gta gac tgc ctc tca ccc ttc act gtc tac ctg ctt 31692
His Leu Glu Val Asp Cys Leu Ser Pro Phe Thr Val Tyr Leu Leu
5990 5995 6000
tac gga ttg gtc acc ctc act ctc atc tgc agc cta atc aca gta 31737
Tyr Gly Leu Val Thr Leu Thr Leu Ile Cys Ser Leu Ile Thr Val
6005 6010 6015
atc atc gcc ttc atc cag tgc att gat tac atc tgt gtg cgc ctc 31782
Ile Ile Ala Phe Ile Gln Cys Ile Asp Tyr Ile Cys Val Arg Leu
6020 6025 6030
gca tac ttc aga cac cac ccg cag tac cga gac agg aac att gcc 31827
Ala Tyr Phe Arg His His Pro Gln Tyr Arg Asp Arg Asn Ile Ala
6035 6040 6045
caa ctt cta aga ctg ctc taatc atg cat aag act gtg atc tgc ctt 31874
Gln Leu Leu Arg Leu Leu Met His Lys Thr Val Ile Cys Leu
6050 6055 6060
ctg atc ctc tgc atc ctg ccc acc ctc acc tcc tgc cag tac acc 31919
Leu Ile Leu Cys Ile Leu Pro Thr Leu Thr Ser Cys Gln Tyr Thr
6065 6070 6075
aca aaa tct ccg cgc aaa aga cat gcc tcc tgc cgc ttc acc caa 31964
Thr Lys Ser Pro Arg Lys Arg His Ala Ser Cys Arg Phe Thr Gln
6080 6085 6090
ctg tgg aat ata ccc aaa tgc tac aac gaa aag agc gag ctc tcc 32009
Leu Trp Asn Ile Pro Lys Cys Tyr Asn Glu Lys Ser Glu Leu Ser
6095 6100 6105
gaa gct tgg ctg tat ggg gtc atc tgt gtc tta gtt ttc tgc agc 32054
Glu Ala Trp Leu Tyr Gly Val Ile Cys Val Leu Val Phe Cys Ser
6110 6115 6120
act gtc ttt gcc ctc atg atc tac ccc tac ttt gat ttg gga tgg 32099
Thr Val Phe Ala Leu Met Ile Tyr Pro Tyr Phe Asp Leu Gly Trp
6125 6130 6135
aac gcg atc gat gcc atg aat tac ccc acc ttt ccc gca ccc gag 32144
Asn Ala Ile Asp Ala Met Asn Tyr Pro Thr Phe Pro Ala Pro Glu
6140 6145 6150
ata att cca ctg cga caa gtt gtg ccc gtt gtc gtt aat caa cgc 32189
Ile Ile Pro Leu Arg Gln Val Val Pro Val Val Val Asn Gln Arg
6155 6160 6165
ccc cca tcc cct acg ccc act gaa atc agc tac ttt aac cta aca 32234
Pro Pro Ser Pro Thr Pro Thr Glu Ile Ser Tyr Phe Asn Leu Thr
6170 6175 6180
ggc gga gat gac tgacgcccta gatctagaaa tggacggcat cagtaccgag 32286
Gly Gly Asp Asp
cagcgtctcc tagagaggcg caggcaggcg gctgagcaag agcgcctcaa tcaggagctc 32346
cgagatctcg ttaacctgca ccagtgcaaa agaggcatct tttgtctggt aaagcaggct 32406
aaagtcacct acgagaagac cggcaacagc caccgcctca gttacaaatt gcccacccag 32466
cgccagaagc tggtgctcat ggtgggtgag aatcccatca ccgtcaccca gcactcggta 32526
gagaccgagg ggtgtctgca ctccccctgt cggggtccag aagacctctg caccctggta 32586
aagaccctgt gcggtctcag agatttagtc ccctttaact aatcaaacac tggaatcaat 32646
aaaaagaatc acttacttaa aatcagacag caggtctctg tccagtttat tcagcagcac 32706
ctccttcccc tcctcccaac tctggtactc caaacgcctt ctggcggcaa acttcctcca 32766
caccctgaag ggaatgtcag attcttgctc ctgtccctcc gcacccacta tcttcatgtt 32826
gttgcag atg aag cgc acc aaa acg tct gac gag agc ttc aac ccc 32872
Met Lys Arg Thr Lys Thr Ser Asp Glu Ser Phe Asn Pro
6185 6190 6195
gtg tac ccc tat gac acg gaa agc ggc cct ccc tcc gtc cct ttc 32917
Val Tyr Pro Tyr Asp Thr Glu Ser Gly Pro Pro Ser Val Pro Phe
6200 6205 6210
ctc acc cct ccc ttc gtg tct ccc gat gga ttc caa gaa agc ccc 32962
Leu Thr Pro Pro Phe Val Ser Pro Asp Gly Phe Gln Glu Ser Pro
6215 6220 6225
ccc ggg gtc ctg tct ctg aac ctg gcc gag ccc ctg gtc act tcc 33007
Pro Gly Val Leu Ser Leu Asn Leu Ala Glu Pro Leu Val Thr Ser
6230 6235 6240
cac ggc atg ctt gcc ctg aaa atg gga agt ggc ctc tcc ctg gac 33052
His Gly Met Leu Ala Leu Lys Met Gly Ser Gly Leu Ser Leu Asp
6245 6250 6255
gac gct ggc aac ctt acc tct caa gat att acc tcc act acc cct 33097
Asp Ala Gly Asn Leu Thr Ser Gln Asp Ile Thr Ser Thr Thr Pro
6260 6265 6270
ccc ctc aaa aaa acc aag acc aac ctc agc cta gaa acc tca tcc 33142
Pro Leu Lys Lys Thr Lys Thr Asn Leu Ser Leu Glu Thr Ser Ser
6275 6280 6285
ccc cta act gta agc acc tca ggc gcc ctc acc gta gca gcc gcc 33187
Pro Leu Thr Val Ser Thr Ser Gly Ala Leu Thr Val Ala Ala Ala
6290 6295 6300
gct ccc ctg gcg gtg gcc ggc acc tcc ctc acc atg caa tca gag 33232
Ala Pro Leu Ala Val Ala Gly Thr Ser Leu Thr Met Gln Ser Glu
6305 6310 6315
gcc ccc ctg gca gta cag gat gca aaa ctc acc ctg gcc acc aaa 33277
Ala Pro Leu Ala Val Gln Asp Ala Lys Leu Thr Leu Ala Thr Lys
6320 6325 6330
ggc ccc ctg acc gtg tct gaa ggc aaa ctg gcc ttg caa aca tcg 33322
Gly Pro Leu Thr Val Ser Glu Gly Lys Leu Ala Leu Gln Thr Ser
6335 6340 6345
gcc ccg ctg acg gcc gct gac agc agc acc ctc acc gtt agc tcc 33367
Ala Pro Leu Thr Ala Ala Asp Ser Ser Thr Leu Thr Val Ser Ser
6350 6355 6360
act cca cca att agt gta agc agt gga agt ttg ggc ttg gac atg 33412
Thr Pro Pro Ile Ser Val Ser Ser Gly Ser Leu Gly Leu Asp Met
6365 6370 6375
gaa gac ccc atg tat act cac gat gga aaa ctg gga ata aga att 33457
Glu Asp Pro Met Tyr Thr His Asp Gly Lys Leu Gly Ile Arg Ile
6380 6385 6390
ggg ggt cca cta aga gta gta gac agc ttg cac aca ctc act gta 33502
Gly Gly Pro Leu Arg Val Val Asp Ser Leu His Thr Leu Thr Val
6395 6400 6405
gtt acc gga aat gga cta act gta gat aac aat gcc ctc caa act 33547
Val Thr Gly Asn Gly Leu Thr Val Asp Asn Asn Ala Leu Gln Thr
6410 6415 6420
aga gtt acg ggc gcc cta ggt tat gac aca tca gga aat cta caa 33592
Arg Val Thr Gly Ala Leu Gly Tyr Asp Thr Ser Gly Asn Leu Gln
6425 6430 6435
ctg aga gcc gca ggg ggt atg cga att gat gca aat ggc caa ctt 33637
Leu Arg Ala Ala Gly Gly Met Arg Ile Asp Ala Asn Gly Gln Leu
6440 6445 6450
atc ctt gat gtg gca tac cca ttt gat gct caa aac aat ctc agc 33682
Ile Leu Asp Val Ala Tyr Pro Phe Asp Ala Gln Asn Asn Leu Ser
6455 6460 6465
ctt aga ctt ggt cag gga ccc ctg tat gta aat aca gac cac aac 33727
Leu Arg Leu Gly Gln Gly Pro Leu Tyr Val Asn Thr Asp His Asn
6470 6475 6480
ctg gat tta aat tgc aac aga ggt cta acc aca act acc acc aac 33772
Leu Asp Leu Asn Cys Asn Arg Gly Leu Thr Thr Thr Thr Thr Asn
6485 6490 6495
aac aca aaa aaa ctt gag act aaa att agc tca ggc tta gac tat 33817
Asn Thr Lys Lys Leu Glu Thr Lys Ile Ser Ser Gly Leu Asp Tyr
6500 6505 6510
gac acc aat ggt gct gtc att att aaa ctt ggc act ggt cta agc 33862
Asp Thr Asn Gly Ala Val Ile Ile Lys Leu Gly Thr Gly Leu Ser
6515 6520 6525
ttc gac aac aca ggc gcc cta act gtg gga aac act ggt gat gat 33907
Phe Asp Asn Thr Gly Ala Leu Thr Val Gly Asn Thr Gly Asp Asp
6530 6535 6540
aaa ctg act ctg tgg acg acc cca gac cca tct cca aat tgc aga 33952
Lys Leu Thr Leu Trp Thr Thr Pro Asp Pro Ser Pro Asn Cys Arg
6545 6550 6555
att cac tca gac aaa gac tgc aag ttt act ctc gtc cta act aag 33997
Ile His Ser Asp Lys Asp Cys Lys Phe Thr Leu Val Leu Thr Lys
6560 6565 6570
tgt gga agc caa atc ctg gcc tct gtc gcc gcc cta gcg gta tca 34042
Cys Gly Ser Gln Ile Leu Ala Ser Val Ala Ala Leu Ala Val Ser
6575 6580 6585
gga aat ctg gct tcg ata aca ggc acc gtt gcc agc gtt acc atc 34087
Gly Asn Leu Ala Ser Ile Thr Gly Thr Val Ala Ser Val Thr Ile
6590 6595 6600
ttt ctt aga ttt gat cag aat gga gtg ctt atg gaa aac tcc tca 34132
Phe Leu Arg Phe Asp Gln Asn Gly Val Leu Met Glu Asn Ser Ser
6605 6610 6615
cta gac aag cag tac tgg aac ttc aga aat ggc aat tca act aat 34177
Leu Asp Lys Gln Tyr Trp Asn Phe Arg Asn Gly Asn Ser Thr Asn
6620 6625 6630
gct gcc ccc tac acc aac gca gtt ggg ttc atg cca aac ctc gca 34222
Ala Ala Pro Tyr Thr Asn Ala Val Gly Phe Met Pro Asn Leu Ala
6635 6640 6645
gcg tac ccc aaa acg caa agc cag act gct aaa aac aac att gta 34267
Ala Tyr Pro Lys Thr Gln Ser Gln Thr Ala Lys Asn Asn Ile Val
6650 6655 6660
agt cag gtt tac ttg aat gga gac aaa tcc aaa ccc atg acc ctt 34312
Ser Gln Val Tyr Leu Asn Gly Asp Lys Ser Lys Pro Met Thr Leu
6665 6670 6675
acc atc acc ctc aat gga act aat gaa tcc agt gaa act agt cag 34357
Thr Ile Thr Leu Asn Gly Thr Asn Glu Ser Ser Glu Thr Ser Gln
6680 6685 6690
gtg agt cac tac tcc atg tca ttt aca tgg gct tgg gaa agc ggg 34402
Val Ser His Tyr Ser Met Ser Phe Thr Trp Ala Trp Glu Ser Gly
6695 6700 6705
caa tat gcc act gaa acc ttt gcc acc aac tcc ttc acc ttt tct 34447
Gln Tyr Ala Thr Glu Thr Phe Ala Thr Asn Ser Phe Thr Phe Ser
6710 6715 6720
tac att gct gaa caa taaaaagcat gacgctgatg ttcatttctg attcttattt 34502
Tyr Ile Ala Glu Gln
6725
tattattttc aaacacaaca aaatcattca agtcattctt ccatcttagc ttaatagaca 34562
cagtagctta atagacccag tagtgcaaag ccccattcta gcttataaat cagacagtga 34622
taattaacca ccaccaccat accttttgat tcaggaaatc atgatcatca caggatccta 34682
gtcttcaggc cgccccctcc ctcccaagac acagaataca cagtcctctc cccccgactg 34742
gctttaaata acaccatctg gttggtcaca gacatgttct taggggttat attccacacg 34802
gtctcctgcc gcgccaggcg ctcgtcggtg atgttgataa actctcccgg cagctcgctc 34862
aagttcacgt cgctgtccag cggctgaacc tccggctgac gcgataactg tgcgaccggc 34922
tgctggacga acggaggccg cgcctacaag ggggtagagt cataattctc ggtcaggata 34982
gggcggtgat gcagcagcag cgagcgaaac atctgctgcc gccgccgctc cgtccggcag 35042
gaaaacaaca cgccggtggt ctcctccgcg ataatccgca ccgcccgcag catcagcttc 35102
ctcgttctcc gcgcgcagca ccgcaccctg atctcgctca agtcggcgca gtaggtacag 35162
cacagcacca cgatgttatt catgatccca cagtgcaggg cgctgtatcc aaagctcatg 35222
ccgggaacca ccgcccccac gtggccatcg taccacaagc gcacgtaaat caagtgtcga 35282
cccctcatga acgtgctgga cacaaacatt acttccttgg gcatgttgta attcaccacc 35342
tcccggtacc agataaacct ctggttgaac acggcacctt ccaccaccat cctgaaccaa 35402
gaggccagaa cctgcccacc ggctatgcac tgcagggaac ccgggttgga acaatgacaa 35462
tgcagactcc aaggctcgta accgtggatc atccggctgc tgaaggcatc gatgttggca 35522
caacacagac acacgtgcat gcactttctc atgattagca gctcttccct cgtcaggatc 35582
atatcccaag gaataaccca ttcttgaatc aacgtaaaac ccacacagca gggaaggcct 35642
cgcacataac tcacattgtg catggtcagc gtgttgcatt ccggaaacag cggatgatcc 35702
tccagtatcg aggcgcgggt ctcgttctca cagggaggta aagggtccct gctgtacgga 35762
ctgtgccggg acgaccgaga tcgtgttgag cgtagtgtca tggaaaaggg aacgccggac 35822
gtggtcatac ttcttgaagc agaaccaggt tcgcgcgtgg caggcctcct tgcgtctgcg 35882
gtctcgccgt ctagctcgct ccgtgtgata attgtagtac agccactccc gcagagcgtc 35942
gaggcgcacc ctggcttccg gatctatgta gactccgtct tgcaccgcgg ccctgataat 36002
atccaccacc gtagaataag caacacccag ccaagcaata cactcgctct gcgagcggca 36062
gacaggagga gcgggcagag atgggagaac catgataaaa aacttttttt taaagaatat 36122
tttccaattc ttcgaaagta agatctatca agtggcagcg ctcccctcca ctggcgcggt 36182
caaactctac ggccaaagca cagacaacgg catttctaag atgttcctta atggcgtcca 36242
aaagacacac cgctctcaag ttgcagtaaa ctatgaatga aaacccatcc ggctgatttt 36302
ccaatataga cgcgccggcg gcgtccacca aacccagata attttcttct ctccagcggt 36362
ttagaatctg tctaagcaaa tcccttatat caagtccggc catgccaaaa atctgctcaa 36422
gagcgccctc caccttcatg accaagcagc gcatcatgat tgcaaaaatt caggttcttc 36482
agagacctgt ataagattca aaatgggaac attaacaaaa attcctctgt cgcgcagatc 36542
ccttcgcagg gcaagctgaa cataatcaga caggtctgaa cggaccagtg aggccaaatc 36602
cccaccagga accagatcca gagaccctat actgattatg acgcgcatac tcggggctat 36662
gctgaccagc gtagcgccga tgtaggcgtg ctgcatgggc ggcgagataa aatgcaaagt 36722
gctggttaaa aaatcaggca aagcctcgcg caaaaaagct aacacatcat aatcatgctc 36782
atgcagatag ttgcaggtaa gctcaggaac caaaacggaa taacacacga ttttcctctc 36842
aaacatgact tcgcggatac tgcgtaaaac aaaaattaca aataaaaaat taattaaata 36902
acttaaacat tggaagcctg tctcacaaca ggaaaaacca ctttaatcaa cataagacgg 36962
gccacgggca tgccggcata gccgtaaaaa aattggtccc cgtgattaac aagtaccaca 37022
gacagctccc cggtcatgtc gggggtcatc atgtgagact ctgtatacac gtctggattg 37082
tgaacatcag acaaacaaag aaatcgagcc acgtagcccg gaggtataat cacccgcagg 37142
cggaggtaca gcaaaacgac ccccatagga ggaatcacaa aattagtagg agaaaaaaat 37202
acataaacac cagaaaaacc ctgttgctga ggcaaaatag cgccctcccg atccaaaaca 37262
acataaagcg cttccacagg agcagccata acaaagaccc gagtcttacc agtaaaagaa 37322
aaaagatctc tcaacgcagc accagcacca acacttcgca gtgtaaaagg ccaagtgccg 37382
agagagtata tataggaata aaaagtgacg taaacgggca aagtccaaaa aacgcccaga 37442
aaaaccgcac gcgaacctac gccccgaaac gaaagccaaa aaacactaga cactcccttc 37502
cggcgtcaac ttccgctttc ccacgctacg tcacttcccc cagtcaaaca aactacgtat 37562
cccgaacttc caagtcgcca cgcccaaaac accgcctaca cctccccgcc cgccggcccg 37622
cccccggacc cgcctcccgc cccgcgcccc gccccgcgcc acccatctca ttatcatatt 37682
ggcttcaatc caaaataagg tatattattg atgatg 37718
<210> 2
<211> 507
<212> PRT
<213> Simian adenovirus 40
<400> 2
Met Glu Arg Arg Asp Pro Leu Glu Phe Gly Leu Arg Pro Gly Phe Ser
1 5 10 15
Gly His Ala Thr Val Glu Ser Met Asp Gln Thr Gln Glu Gln Ala Ala
20 25 30
Thr Val Val Phe Arg Pro Pro Val Ala Asp Ser Gly Gly Gly Ala Thr
35 40 45
Gly Arg Val Arg Gly Pro Gly Pro Ser Gly Ser Gly Gly Glu Gly Thr
50 55 60
Glu Ala Gly Arg Glu Glu Arg Ala Glu Pro Gly Asn Arg Ala Glu Arg
65 70 75 80
Pro Ser Thr Ser Gly Val Asn Val Gly Gln Val Val Asp Leu Phe Pro
85 90 95
Glu Leu Arg Arg Ile Leu Thr Ile Arg Glu Asp Gly Gln Phe Val Lys
100 105 110
Gly Leu Lys Arg Glu Arg Gly Ala Ser Glu His Asn Glu Glu Ala Ser
115 120 125
Asn Leu Ala Phe Ser Leu Met Thr Arg His Arg Pro Glu Cys Ile Thr
130 135 140
Phe Gln Gln Ile Lys Asp Asn Cys Ala Asn Glu Leu Asp Leu Leu Gly
145 150 155 160
Gln Lys Tyr Ser Ile Glu Gln Leu Thr Thr Tyr Trp Leu Gln Pro Gly
165 170 175
Asp Asp Leu Glu Glu Ala Ile Arg Val Tyr Ala Lys Val Ala Leu Arg
180 185 190
Pro Asp Cys Lys Tyr Lys Leu Lys Gly Leu Val Asn Ile Arg Asn Cys
195 200 205
Cys Tyr Ile Ser Gly Asn Gly Ala Glu Val Glu Ile Glu Thr Glu Asp
210 215 220
Arg Val Ala Phe Arg Cys Ser Met Met Asn Met Trp Pro Gly Val Leu
225 230 235 240
Gly Met Asp Gly Val Val Ile Met Asn Val Arg Phe Thr Gly Pro Asn
245 250 255
Phe Asn Gly Thr Val Phe Leu Gly Asn Thr Asn Leu Val Leu His Gly
260 265 270
Val Ser Phe Tyr Gly Phe Asn Asn Thr Cys Val Glu Ala Trp Thr Asp
275 280 285
Val Lys Val Arg Gly Cys Ala Phe Tyr Gly Cys Trp Lys Ala Ile Val
290 295 300
Ser Arg Pro Lys Ser Arg Ser Ser Ile Lys Lys Cys Leu Phe Glu Arg
305 310 315 320
Cys Thr Leu Gly Ile Leu Ala Glu Gly Asn Cys Arg Val Arg His Asn
325 330 335
Val Ala Ser Glu Cys Gly Cys Phe Met Leu Val Lys Ser Val Ala Val
340 345 350
Ile Lys His Asn Met Val Cys Gly Asn Ser Glu Asp Lys Ala Ser Gln
355 360 365
Met Leu Thr Cys Thr Asp Gly Asn Cys His Leu Leu Lys Thr Ile His
370 375 380
Val Thr Ser His Ser Arg Lys Ala Trp Pro Val Phe Glu His Asn Leu
385 390 395 400
Leu Thr Arg Cys Ser Leu His Leu Gly Asn Arg Arg Gly Val Phe Leu
405 410 415
Pro Tyr Gln Cys Asn Phe Ser His Thr Lys Ile Leu Leu Glu Pro Glu
420 425 430
Ser Met Ser Lys Val Asn Leu Asn Gly Val Phe Asp Met Thr Met Lys
435 440 445
Ile Trp Lys Val Leu Arg Tyr Asp Glu Thr Arg Ser Arg Cys Arg Pro
450 455 460
Cys Glu Cys Gly Gly Lys His Met Arg Asn Gln Pro Val Met Leu Asp
465 470 475 480
Val Thr Glu Glu Leu Arg Thr Asp His Leu Val Leu Ala Cys Thr Arg
485 490 495
Ala Glu Phe Gly Ser Ser Asp Glu Asp Thr Asp
500 505
<210> 3
<211> 153
<212> PRT
<213> Simian adenovirus 40
<400> 3
Met Ser Gly Ser Ser Ser Ser Ser Ser Ser Ser Ala Leu Asp Gly Ser
1 5 10 15
Ile Val Ser Pro Tyr Leu Thr Thr Arg Met Pro His Trp Ala Gly Val
20 25 30
Arg Gln Asn Val Met Gly Ser Ser Ile Asp Gly Arg Pro Val Leu Pro
35 40 45
Ala Asn Ser Ala Thr Leu Thr Tyr Ala Thr Val Ala Gly Thr Pro Leu
50 55 60
Asp Ala Thr Ala Ala Ala Ala Ala Thr Ala Ala Ala Ser Ala Val Arg
65 70 75 80
Ser Leu Ala Thr Asp Phe Ala Phe Leu Gly Pro Leu Ala Thr Gly Ala
85 90 95
Thr Ser Arg Ala Ala Ala Ala Ala Val Arg Asp Asp Lys Leu Thr Ala
100 105 110
Leu Leu Ala Gln Leu Asp Ala Leu Thr Arg Glu Leu Gly Asp Leu Ser
115 120 125
Gln Gln Val Met Ala Leu Arg Gln Gln Val Ser Ser Leu Gln Ala Gly
130 135 140
Gly Asn Ala Ser Pro Thr Asn Ala Val
145 150
<210> 4
<211> 419
<212> PRT
<213> Simian adenovirus 40
<400> 4
Met His Pro Val Leu Arg Gln Met Arg Pro Pro Pro Gln Gln Gln Gln
1 5 10 15
Gln His Gln Gln Glu Arg Gln Gln Gln Gln Arg Glu Ser Cys Arg Ala
20 25 30
Pro Ser Pro Thr Leu Gly Gly Pro Ala Thr Ser Ala Ser Ala Ala Val
35 40 45
Ser Gly Ala Cys Gly Gly Gly Gly Gly Pro Ala Asp Asp Pro Glu Glu
50 55 60
Pro Pro Arg Arg Arg Ala Arg His Tyr Leu Asp Leu Glu Glu Gly Glu
65 70 75 80
Gly Leu Ala Arg Leu Gly Ala Pro Ser Pro Glu Arg His Pro Arg Val
85 90 95
Gln Leu Lys Arg Asp Ser Arg Glu Ala Tyr Val Pro Arg Gln Asn Leu
100 105 110
Phe Arg Asp Arg Ala Gly Glu Glu Pro Glu Glu Met Arg Asp Arg Arg
115 120 125
Phe Ser Ala Gly Arg Glu Leu Arg Gln Gly Leu Asn Arg Glu Arg Leu
130 135 140
Leu Arg Glu Glu Asp Phe Glu Pro Asp Ala Arg Thr Gly Ile Ser Pro
145 150 155 160
Ala Arg Ala His Val Ala Ala Ala Asp Leu Val Thr Ala Tyr Glu Gln
165 170 175
Thr Val Asn Gln Glu Ile Asn Phe Gln Lys Ser Phe Asn Asn His Val
180 185 190
Arg Thr Leu Val Ala Arg Glu Glu Val Thr Ile Gly Leu Met His Leu
195 200 205
Trp Asp Phe Val Ser Ala Leu Val Gln Asn Pro Asn Ser Lys Pro Leu
210 215 220
Thr Ala Gln Leu Phe Leu Ile Val Gln His Ser Arg Asp Asn Glu Ala
225 230 235 240
Phe Arg Asp Ala Leu Leu Asn Ile Thr Glu Pro Glu Gly Arg Trp Leu
245 250 255
Leu Asp Leu Ile Asn Ile Leu Gln Ser Ile Val Val Gln Glu Arg Ser
260 265 270
Leu Ser Leu Ala Asp Lys Val Ala Ala Ile Asn Tyr Ser Met Leu Ser
275 280 285
Leu Gly Lys Phe Tyr Ala Arg Lys Ile Tyr Gln Thr Pro Tyr Val Pro
290 295 300
Ile Asp Lys Glu Val Lys Ile Asp Gly Phe Tyr Met Arg Met Ala Leu
305 310 315 320
Lys Val Leu Thr Leu Ser Asp Asp Leu Gly Val Tyr Arg Asn Glu Arg
325 330 335
Ile His Lys Ala Val Ser Val Ser Arg Arg Arg Glu Leu Ser Asp Arg
340 345 350
Glu Leu Met His Ser Leu Gln Arg Ala Leu Ala Gly Ala Gly Ser Gly
355 360 365
Asp Arg Glu Ala Glu Ser Tyr Phe Asp Ala Gly Ala Asp Leu Arg Trp
370 375 380
Ala Pro Ser Arg Arg Ala Leu Glu Ala Ala Gly Val Arg Glu Asp Tyr
385 390 395 400
Asp Glu Asp Gly Glu Glu Asp Glu Glu Tyr Glu Leu Glu Glu Gly Glu
405 410 415
Tyr Leu Asp
<210> 5
<211> 591
<212> PRT
<213> Simian adenovirus 40
<400> 5
Met Gln Asp Pro Asn Val Val Asp Pro Ala Leu Arg Ala Ala Leu Gln
1 5 10 15
Ser Gln Pro Ser Gly Leu Asn Ser Ser Asp Asp Trp Arg Gln Val Met
20 25 30
Asp Arg Ile Met Ser Leu Thr Ala Arg Asn Pro Asp Ala Phe Arg Gln
35 40 45
Gln Pro Gln Ala Asn Arg Leu Ser Ala Ile Leu Glu Ala Val Val Pro
50 55 60
Ala Arg Ser Asn Pro Thr His Glu Lys Val Leu Ala Ile Val Asn Ala
65 70 75 80
Leu Ala Glu Asn Arg Ala Ile Arg Pro Asp Glu Ala Gly Leu Val Tyr
85 90 95
Asp Ala Leu Leu Gln Arg Val Ala Arg Tyr Asn Ser Gly Asn Val Gln
100 105 110
Thr Asn Leu Asp Arg Leu Val Gly Asp Val Arg Glu Ala Val Ala Gln
115 120 125
Arg Glu Arg Ala Asp Arg Gln Gly Asn Leu Gly Ser Met Val Ala Leu
130 135 140
Asn Ala Phe Leu Ser Thr Gln Pro Ala Asn Val Pro Arg Gly Gln Glu
145 150 155 160
Asp Tyr Thr Asn Phe Val Ser Ala Leu Arg Leu Met Val Thr Glu Thr
165 170 175
Pro Gln Ser Glu Val Tyr Gln Ser Gly Pro Asp Tyr Phe Phe Gln Thr
180 185 190
Ser Arg Gln Gly Leu Gln Thr Val Asn Leu Ser Gln Ala Phe Lys Asn
195 200 205
Leu Arg Gly Leu Trp Gly Val Lys Ala Pro Thr Gly Asp Arg Ala Thr
210 215 220
Val Ser Ser Leu Leu Thr Pro Asn Ser Arg Leu Leu Leu Leu Leu Ile
225 230 235 240
Ala Pro Phe Thr Asp Ser Gly Ser Val Ser Arg Asp Thr Tyr Leu Gly
245 250 255
His Leu Leu Thr Leu Tyr Arg Glu Ala Ile Gly Gln Ala Gln Val Asp
260 265 270
Glu His Thr Phe Gln Glu Ile Thr Ser Val Ser Arg Ala Leu Gly Gln
275 280 285
Glu Asp Thr Ser Ser Leu Glu Ala Thr Leu Asn Tyr Leu Leu Thr Asn
290 295 300
Arg Arg Gln Lys Ile Pro Ser Leu His Ser Leu Thr Ser Glu Glu Glu
305 310 315 320
Arg Ile Leu Arg Tyr Val Gln Gln Ser Val Ser Leu Asn Leu Met Arg
325 330 335
Asp Gly Val Thr Pro Ser Val Ala Leu Asp Met Thr Ala Arg Asn Met
340 345 350
Glu Pro Gly Met Tyr Ala Ala His Arg Pro Tyr Ile Asn Arg Leu Met
355 360 365
Asp Tyr Leu His Arg Ala Ala Ala Val Asn Pro Glu Tyr Phe Thr Asn
370 375 380
Ala Ile Leu Asn Pro His Trp Leu Pro Pro Pro Gly Phe Tyr Ser Gly
385 390 395 400
Gly Phe Glu Val Pro Glu Ala Asn Asp Gly Phe Leu Trp Asp Asp Met
405 410 415
Asp Asp Ser Val Phe Ser Pro Arg Pro Gln Ala Leu Ala Glu Ala Ser
420 425 430
Leu Leu Arg Pro Lys Lys Glu Glu Glu Ala Ser Arg Arg Arg Gly Ser
435 440 445
Ser Gly Val Ala Ser Leu Ser Glu Leu Gly Ala Ala Ala Ala Ala Arg
450 455 460
Pro Gly Ser Leu Gly Gly Ser Pro Phe Pro Ser Leu Val Gly Ser Leu
465 470 475 480
His Ser Glu Arg Thr Thr Arg Pro Arg Leu Leu Gly Glu Asp Glu Tyr
485 490 495
Leu Asn Asn Ser Leu Leu Gln Pro Val Arg Glu Lys Asn Leu Pro Pro
500 505 510
Ala Phe Pro Asn Asn Gly Ile Glu Ser Leu Val Asp Lys Met Ser Arg
515 520 525
Trp Lys Thr Tyr Ala Gln Glu His Arg Asp Ala Pro Ala Leu Arg Pro
530 535 540
Pro Thr Arg Arg Gln Arg His Asp Arg Gln Arg Gly Leu Val Trp Asp
545 550 555 560
Asp Glu Asp Ser Ala Asp Asp Ser Ser Val Leu Asp Leu Gly Gly Ser
565 570 575
Gly Asn Pro Phe Ala His Leu Arg Pro Arg Leu Gly Arg Met Phe
580 585 590
<210> 6
<211> 593
<212> PRT
<213> Simian adenovirus 40
<400> 6
Met Arg Arg Ala Ala Met Tyr Gln Glu Gly Pro Pro Pro Ser Tyr Glu
1 5 10 15
Ser Val Val Gly Ala Ala Ala Ala Ala Pro Ser Ser Pro Phe Ala Ser
20 25 30
Gln Leu Leu Glu Pro Pro Tyr Val Pro Pro Arg Tyr Leu Arg Pro Thr
35 40 45
Gly Gly Arg Asn Ser Ile Arg Tyr Ser Glu Leu Ala Pro Leu Phe Asp
50 55 60
Thr Thr Arg Val Tyr Leu Val Asp Asn Lys Ser Ala Asp Val Ala Ser
65 70 75 80
Leu Asn Tyr Gln Asn Asp His Ser Asn Phe Leu Thr Thr Val Ile Gln
85 90 95
Asn Asn Asp Tyr Ser Pro Ser Glu Ala Ser Thr Gln Thr Ile Asn Leu
100 105 110
Asp Asp Arg Ser His Trp Gly Gly Asp Leu Lys Thr Ile Leu His Thr
115 120 125
Asn Met Pro Asn Val Asn Glu Phe Met Phe Thr Asn Lys Phe Lys Ala
130 135 140
Arg Val Met Val Ser Arg Ser His Thr Lys Glu Asp Arg Val Glu Leu
145 150 155 160
Lys Tyr Glu Trp Val Glu Phe Glu Leu Pro Glu Gly Asn Tyr Ser Glu
165 170 175
Thr Met Thr Ile Asp Leu Met Asn Asn Ala Ile Val Glu His Tyr Leu
180 185 190
Lys Val Gly Arg Gln Asn Gly Val Leu Glu Ser Asp Ile Gly Val Lys
195 200 205
Phe Asp Thr Arg Asn Phe Arg Leu Gly Leu Asp Pro Val Thr Gly Leu
210 215 220
Val Met Pro Gly Val Tyr Thr Asn Glu Ala Phe His Pro Asp Ile Ile
225 230 235 240
Leu Leu Pro Gly Cys Gly Val Asp Phe Thr Tyr Ser Arg Leu Ser Asn
245 250 255
Leu Leu Gly Ile Arg Lys Arg Gln Pro Phe Gln Glu Gly Phe Arg Ile
260 265 270
Thr Tyr Glu Asp Leu Glu Gly Gly Asn Ile Pro Ala Leu Leu Asp Val
275 280 285
Glu Ala Tyr Gln Asp Ser Leu Lys Glu Asn Glu Ala Gly Gln Glu Asp
290 295 300
Thr Ala Pro Ala Ala Ser Ala Ala Ala Glu Gln Gly Glu Asp Ala Ala
305 310 315 320
Asp Thr Ala Ala Ala Asp Gly Ala Glu Ala Asp Pro Ala Met Val Val
325 330 335
Glu Ala Pro Glu Gln Glu Glu Asp Met Asn Asp Ser Ala Val Arg Gly
340 345 350
Asp Thr Phe Val Thr Arg Gly Glu Glu Lys Gln Ala Glu Ala Glu Ala
355 360 365
Ala Ala Glu Glu Lys Gln Leu Ala Ala Ala Ala Ala Ala Ala Ala Leu
370 375 380
Ala Ala Ala Glu Ala Glu Ser Glu Gly Thr Lys Pro Ala Lys Glu Pro
385 390 395 400
Val Ile Lys Pro Leu Thr Glu Asp Ser Lys Lys Arg Ser Tyr Asn Leu
405 410 415
Leu Lys Asp Ser Thr Asn Thr Ala Tyr Arg Ser Trp Tyr Leu Ala Tyr
420 425 430
Asn Tyr Gly Asp Pro Ser Thr Gly Val Arg Ser Trp Thr Leu Leu Cys
435 440 445
Thr Pro Asp Val Thr Cys Gly Ser Glu Gln Val Tyr Trp Ser Leu Pro
450 455 460
Asp Met Met Gln Asp Pro Val Thr Phe Arg Ser Thr Arg Gln Val Ser
465 470 475 480
Asn Phe Pro Val Val Gly Ala Glu Leu Leu Pro Val His Ser Lys Ser
485 490 495
Phe Tyr Asn Asp Gln Ala Val Tyr Ser Gln Leu Ile Arg Gln Phe Thr
500 505 510
Ser Leu Thr His Val Phe Asn Arg Phe Pro Glu Asn Gln Ile Leu Ala
515 520 525
Arg Pro Pro Ala Pro Thr Ile Thr Thr Val Ser Glu Asn Val Pro Ala
530 535 540
Leu Thr Asp His Gly Thr Leu Pro Leu Arg Asn Ser Ile Gly Gly Val
545 550 555 560
Gln Arg Val Thr Val Thr Asp Ala Arg Arg Arg Thr Cys Pro Tyr Val
565 570 575
Tyr Lys Ala Leu Gly Ile Val Ser Pro Arg Val Leu Ser Ser Arg Thr
580 585 590
Phe
<210> 7
<211> 198
<212> PRT
<213> Simian adenovirus 40
<400> 7
Met Ser Ile Leu Ile Ser Pro Ser Asn Asn Ser Gly Trp Gly Leu Leu
1 5 10 15
Arg Ala Pro Ser Lys Met Phe Gly Gly Ala Arg Lys Arg Ser Glu Gln
20 25 30
His Pro Val Arg Val Arg Gly His Phe Arg Ala Pro Trp Gly Ala His
35 40 45
Lys Arg Gly Arg Ala Gly Arg Thr Thr Val Asp Asp Ala Ile Asp Ser
50 55 60
Val Val Glu Gln Ala Arg Asn Tyr Arg Pro Ala Val Ser Thr Val Asp
65 70 75 80
Ala Ala Ile Gln Thr Val Val Arg Gly Ala Arg Arg Tyr Ala Lys Leu
85 90 95
Lys Ser Arg Arg Lys Arg Val Ala Arg Arg His Arg Arg Arg Pro Gly
100 105 110
Ala Ala Ala Lys Arg Ala Ala Ala Ala Leu Leu Arg Arg Ala Lys Arg
115 120 125
Thr Gly Arg Arg Ala Ala Met Arg Ala Ala Arg Arg Leu Ala Ala Gly
130 135 140
Ile Thr Ala Ala Thr Met Ala Pro Arg Thr Arg Arg Arg Ala Ala Ala
145 150 155 160
Ala Ala Ala Ala Ala Ile Ser Asp Met Ala Ser Arg Arg Arg Gly Asn
165 170 175
Val Tyr Trp Val Arg Asp Ser Val Thr Gly Thr Arg Val Pro Val Arg
180 185 190
Phe Arg Pro Pro Arg Thr
195
<210> 8
<211> 371
<212> PRT
<213> Simian adenovirus 40
<400> 8
Met Ser Lys Arg Lys Ile Lys Glu Glu Met Leu Gln Val Val Ala Pro
1 5 10 15
Glu Ile Tyr Gly Pro Pro Lys Lys Glu Glu Gln Asp Ser Lys Pro Arg
20 25 30
Lys Ile Lys Arg Val Lys Lys Lys Lys Lys Asp Asp Asp Asp Ala Asp
35 40 45
Gly Glu Val Glu Phe Leu Arg Ala Thr Ala Pro Arg Arg Pro Val Gln
50 55 60
Trp Lys Gly Arg Arg Val Lys Arg Val Leu Arg Pro Gly Thr Ala Val
65 70 75 80
Val Phe Thr Pro Gly Glu Arg Ser Thr Arg Thr Phe Lys Arg Val Tyr
85 90 95
Asp Glu Val Tyr Gly Asp Glu Asp Leu Leu Glu Gln Ala Asn Glu Arg
100 105 110
Phe Gly Glu Phe Ala Tyr Gly Lys Arg Gln Arg Ala Leu Gly Lys Glu
115 120 125
Asp Leu Leu Ala Leu Pro Leu Asp Gln Gly Asn Pro Thr Pro Ser Leu
130 135 140
Lys Pro Val Thr Leu Gln Gln Val Leu Pro Ser Ser Ala Pro Ser Glu
145 150 155 160
Ala Lys Arg Gly Leu Lys Arg Glu Gly Gly Asp Leu Ala Pro Thr Val
165 170 175
Gln Leu Met Val Pro Lys Arg Gln Arg Leu Glu Asp Val Leu Glu Lys
180 185 190
Met Lys Val Asp Pro Gly Leu Gln Pro Asp Ile Arg Val Arg Pro Ile
195 200 205
Lys Gln Val Ala Pro Gly Leu Gly Val Gln Thr Val Asp Val Val Ile
210 215 220
Pro Thr Gly Asn Ser Pro Ala Ala Thr Thr Thr Thr Ala Ala Ser Thr
225 230 235 240
Asp Met Glu Thr Gln Thr Asp Pro Ala Ala Ala Ala Ala Ala Ala Ala
245 250 255
Ala Ala Thr Ser Ser Ala Glu Val Gln Thr Asp Pro Trp Leu Pro Pro
260 265 270
Ala Met Ser Ala Pro Arg Ala Arg Arg Gly Arg Arg Lys Tyr Gly Ala
275 280 285
Ala Asn Ala Leu Leu Pro Glu Tyr Ala Leu His Pro Ser Ile Ala Pro
290 295 300
Thr Pro Gly Tyr Arg Gly Tyr Thr Tyr Arg Pro Arg Arg Ala Lys Gly
305 310 315 320
Ser Thr Arg Arg Pro Arg Arg Arg Ala Ala Ala Thr Thr Arg Arg Arg
325 330 335
Arg Arg Arg Arg Gln Pro Ala Leu Ala Pro Val Ser Val Arg Arg Val
340 345 350
Ala Arg Asp Gly His Thr Leu Val Leu Pro Arg Ala Arg Tyr His Pro
355 360 365
Ser Ile Val
370
<210> 9
<211> 81
<212> PRT
<213> Simian adenovirus 40
<400> 9
Met Ala Leu Thr Cys Arg Leu Arg Phe Pro Val Pro Gly Tyr Arg Gly
1 5 10 15
Gly Arg Ser Arg Arg Arg Arg Gly Leu Ala Gly Arg Gly Leu Ser Gly
20 25 30
Gly Ser Arg Arg Ala His Arg Arg Arg Arg Ala Thr Ser Arg Arg Met
35 40 45
Arg Gly Gly Val Leu Pro Leu Leu Ile Pro Leu Ile Ala Ala Ala Ile
50 55 60
Gly Ala Val Pro Gly Ile Ala Ser Val Ala Leu Gln Ala Ser Gln Arg
65 70 75 80
His
<210> 10
<211> 251
<212> PRT
<213> Simian adenovirus 40
<400> 10
Met Glu Asp Ile Asn Phe Ala Ser Leu Ala Pro Arg His Gly Ser Arg
1 5 10 15
Pro Phe Leu Gly His Trp Asn Asp Ile Gly Thr Ser Asn Met Ser Gly
20 25 30
Gly Ala Phe Ser Trp Gly Ser Leu Trp Ser Gly Ile Lys Ser Ile Gly
35 40 45
Ser Ala Val Lys Asn Tyr Gly Ser Arg Ala Trp Asn Ser Ser Thr Gly
50 55 60
Gln Met Leu Arg Asp Lys Leu Lys Glu Gln Asn Phe Gln Gln Lys Val
65 70 75 80
Val Glu Gly Leu Ala Ser Gly Ile Asn Gly Val Val Asp Leu Ala Asn
85 90 95
Gln Ala Val Gln Asn Lys Ile Asn Ser Arg Leu Asp Pro Arg Pro Pro
100 105 110
Val Glu Glu Val Pro Pro Ala Leu Glu Thr Val Ser Pro Asp Gly Arg
115 120 125
Gly Glu Lys Arg Pro Arg Pro Asp Arg Glu Glu Thr Thr Leu Val Thr
130 135 140
Gln Thr Asp Glu Pro Pro Pro Tyr Glu Glu Ala Leu Lys Gln Gly Leu
145 150 155 160
Pro Thr Thr Arg Pro Ile Ala Pro Met Ala Thr Gly Val Val Gly Arg
165 170 175
His Thr Pro Ala Thr Leu Asp Leu Pro Pro Pro Ala Asp Val Pro Gln
180 185 190
Gln Gln Lys Ala Ala Gln Pro Gly Pro Pro Ala Thr Ala Ser Arg Ser
195 200 205
Ser Ala Gly Pro Leu Arg Arg Ala Ala Ser Gly Pro Arg Gly Gly Val
210 215 220
Ala Arg His Gly Asn Trp Gln Ser Thr Leu Asn Ser Ile Val Gly Leu
225 230 235 240
Gly Val Arg Ser Val Lys Arg Arg Arg Cys Tyr
245 250
<210> 11
<211> 960
<212> PRT
<213> Simian adenovirus 40
<400> 11
Met Ala Thr Pro Ser Met Met Pro Gln Trp Ser Tyr Met His Ile Ser
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Glu Ser Tyr Phe Ser Leu Ser Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Thr Leu Arg Phe Ile Pro Val Asp Arg Glu Asp Thr Ala Tyr Ser Tyr
65 70 75 80
Lys Ala Arg Phe Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Thr
100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125
Ala Pro Asn Ser Cys Glu Trp Glu Gln Glu Glu Thr Gln Ala Val Glu
130 135 140
Glu Ala Ala Glu Glu Glu Glu Glu Asp Ala Asp Gly Gln Ala Glu Glu
145 150 155 160
Glu Gln Ala Ala Thr Lys Lys Thr His Val Tyr Ala Gln Ala Pro Leu
165 170 175
Ser Gly Glu Lys Ile Ser Lys Asp Gly Leu Gln Ile Gly Thr Asp Ala
180 185 190
Thr Ala Thr Glu Gln Lys Pro Ile Tyr Ala Asp Pro Thr Phe Gln Pro
195 200 205
Glu Pro Gln Ile Gly Glu Ser Gln Trp Asn Glu Ala Asp Ala Thr Val
210 215 220
Ala Gly Gly Arg Val Leu Lys Lys Ser Thr Pro Met Lys Pro Cys Tyr
225 230 235 240
Gly Ser Tyr Ala Arg Pro Thr Asn Ala Asn Gly Gly Gln Gly Val Leu
245 250 255
Thr Ala Asn Ala Gln Gly Gln Leu Glu Ser Gln Val Glu Met Gln Phe
260 265 270
Phe Ser Thr Ser Glu Asn Ala Arg Asn Glu Thr Asn Asn Ile Gln Pro
275 280 285
Lys Leu Val Leu Tyr Ser Glu Asp Val His Met Glu Thr Pro Asp Thr
290 295 300
His Leu Ser Tyr Lys Pro Ala Lys Ser Asp Asp Asn Ser Lys Ile Met
305 310 315 320
Leu Gly Gln Gln Ser Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg
325 330 335
Asp Asn Phe Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly
340 345 350
Val Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln
355 360 365
Asp Arg Asn Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Met Gly
370 375 380
Asp Arg Thr Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr
385 390 395 400
Asp Pro Asp Val Arg Ile Ile Glu Asn His Gly Thr Glu Asp Glu Leu
405 410 415
Pro Asn Tyr Cys Phe Pro Leu Gly Gly Ile Gly Val Thr Asp Thr Tyr
420 425 430
Gln Ala Val Lys Thr Asn Asn Gly Asn Asn Gly Gly Gln Val Thr Trp
435 440 445
Thr Lys Asp Glu Thr Phe Ala Asp Arg Asn Glu Ile Gly Val Gly Asn
450 455 460
Asn Phe Ala Met Glu Ile Asn Leu Ser Ala Asn Leu Trp Arg Asn Phe
465 470 475 480
Leu Tyr Ser Asn Val Ala Leu Tyr Leu Pro Asp Lys Leu Lys Tyr Asn
485 490 495
Pro Ser Asn Val Asp Ile Ser Asp Asn Pro Asn Thr Tyr Asp Tyr Met
500 505 510
Asn Lys Arg Val Val Ala Pro Gly Leu Val Asp Cys Tyr Ile Asn Leu
515 520 525
Gly Ala Arg Trp Ser Leu Asp Tyr Met Asp Asn Val Asn Pro Phe Asn
530 535 540
His His Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn
545 550 555 560
Gly Arg Tyr Val Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala
565 570 575
Ile Lys Asn Leu Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn
580 585 590
Phe Arg Lys Asp Val Asn Met Val Leu Gln Ser Ser Leu Gly Asn Asp
595 600 605
Leu Arg Val Asp Gly Ala Ser Ile Lys Phe Glu Ser Ile Cys Leu Tyr
610 615 620
Ala Thr Phe Phe Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala
625 630 635 640
Met Leu Arg Asn Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser
645 650 655
Ala Ala Asn Met Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Val Pro
660 665 670
Ile Ser Ile Pro Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ala Phe
675 680 685
Thr Arg Leu Lys Thr Lys Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp
690 695 700
Pro Tyr Tyr Thr Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe
705 710 715 720
Tyr Leu Asn His Thr Phe Lys Lys Val Ser Val Thr Phe Asp Ser Ser
725 730 735
Val Ser Trp Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu
740 745 750
Ile Lys Arg Ser Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn
755 760 765
Met Thr Lys Asp Trp Phe Leu Val Gln Met Leu Ala Asn Tyr Asn Ile
770 775 780
Gly Tyr Gln Gly Phe Tyr Ile Pro Glu Ser Tyr Lys Asp Arg Met Tyr
785 790 795 800
Ser Phe Phe Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp Gln
805 810 815
Thr Lys Tyr Lys Asp Tyr Gln Glu Val Gly Ile Ile His Gln His Asn
820 825 830
Asn Ser Gly Phe Val Gly Tyr Leu Ala Pro Thr Met Arg Glu Gly Gln
835 840 845
Ala Tyr Pro Ala Asn Phe Pro Tyr Pro Leu Ile Gly Lys Thr Ala Val
850 855 860
Asp Ser Ile Thr Gln Lys Lys Phe Leu Cys Asp Arg Thr Leu Trp Arg
865 870 875 880
Ile Pro Phe Ser Ser Asn Phe Met Ser Met Gly Ala Leu Ser Asp Leu
885 890 895
Gly Gln Asn Leu Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Thr
900 905 910
Phe Glu Val Asp Pro Met Asp Glu Pro Thr Leu Leu Tyr Val Leu Phe
915 920 925
Glu Val Phe Asp Val Val Arg Val His Gln Pro His Arg Gly Val Ile
930 935 940
Glu Thr Val Tyr Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr
945 950 955 960
<210> 12
<211> 209
<212> PRT
<213> Simian adenovirus 40
<400> 12
Met Pro Ser Gly Ser Thr Glu Gln Glu Leu Arg Ala Ile Val Arg Asp
1 5 10 15
Leu Gly Cys Gly Pro Tyr Phe Leu Gly Thr Phe Asp Lys Arg Phe Pro
20 25 30
Gly Phe Val Ser Pro His Lys Leu Ala Cys Ala Ile Val Asn Thr Ala
35 40 45
Gly Arg Glu Thr Gly Gly Val His Trp Leu Ala Phe Ala Trp Asn Pro
50 55 60
Arg Ser Lys Thr Cys Phe Leu Phe Asp Pro Phe Gly Phe Ser Asp Gln
65 70 75 80
Arg Leu Lys Gln Ile Tyr Glu Phe Glu Tyr Glu Gly Leu Leu Arg Arg
85 90 95
Ser Ala Ile Ala Ser Ser Pro Asp Arg Cys Val Thr Leu Glu Lys Ser
100 105 110
Thr Gln Thr Val Gln Gly Pro Asp Ser Ala Ala Cys Gly Leu Phe Cys
115 120 125
Cys Met Phe Leu His Ala Phe Val His Trp Pro Gln Ser Pro Met Asp
130 135 140
Arg Asn Pro Thr Met Asn Leu Leu Thr Gly Val Pro Asn Ser Met Leu
145 150 155 160
Gln Ser Pro Gln Val Glu Pro Thr Leu Arg Arg Asn Gln Glu Gln Leu
165 170 175
Tyr Ser Phe Leu Glu Arg His Ser Pro Tyr Phe Arg Arg His Ser Ala
180 185 190
Gln Ile Arg Arg Ala Thr Ser Phe Cys His Leu Gln Glu Met Gln Glu
195 200 205
Gly
<210> 13
<211> 834
<212> PRT
<213> Simian adenovirus 40
<400> 13
Met Glu Ser Leu Met Arg Val Glu Lys Glu Glu Asp Ser Leu Thr Ala
1 5 10 15
Pro Ser Glu Pro Ser Thr Thr Ala Ala Thr Thr Ala Asn Ala Ala Ala
20 25 30
Asp Asp Ala Pro Thr Glu Thr Thr Ala Ser Thr Thr Leu Pro Ser Asp
35 40 45
Ala Pro Pro Leu Glu Asn Glu Val Leu Ile Glu Gln Asp Pro Gly Phe
50 55 60
Val Ser Gly Glu Glu Asp Glu Val Asp Glu Lys Glu Lys Glu Glu Val
65 70 75 80
Ala Ala Ser Val Pro Lys Glu Asp Lys Lys Gln Asp Gln Asp Asp Ala
85 90 95
Asp Lys Asp Glu Thr Ala Val Gly Arg Gly Asn Gly Ser His Asp Ala
100 105 110
Asp Asp Gly Tyr Leu Asp Val Gly Asp Asp Val Leu Leu Lys His Leu
115 120 125
His Arg Gln Cys Val Ile Val Cys Asp Ala Leu Gln Glu Arg Cys Glu
130 135 140
Val Pro Leu Asp Val Ala Glu Val Ser Arg Ala Tyr Glu Arg His Leu
145 150 155 160
Phe Ala Pro His Val Pro Pro Lys Arg Arg Glu Asn Gly Thr Cys Glu
165 170 175
Pro Asn Pro Arg Leu Asn Phe Tyr Pro Val Phe Ala Val Pro Glu Val
180 185 190
Leu Ala Thr Tyr His Ile Phe Phe Gln Asn Cys Lys Ile Pro Leu Ser
195 200 205
Cys Arg Ala Asn Arg Thr Arg Ala Asp Lys Thr Leu Thr Leu Arg Gln
210 215 220
Gly Ala His Ile Pro Asp Ile Ala Ser Leu Glu Glu Val Pro Lys Ile
225 230 235 240
Phe Glu Gly Leu Gly Arg Asp Glu Lys Arg Ala Ala Asn Ala Leu His
245 250 255
Gly Asp Ser Glu Asn Glu Ser His Ser Gly Val Leu Val Glu Leu Glu
260 265 270
Gly Asp Asn Ala Arg Leu Ala Val Leu Lys Arg Ser Ile Glu Val Thr
275 280 285
His Phe Ala Tyr Pro Ala Leu Asn Leu Pro Pro Lys Val Met Ser Val
290 295 300
Val Met Gly Glu Leu Ile Met Arg Arg Ala Gln Pro Leu Ala Ala Asp
305 310 315 320
Ala Asn Leu Gln Glu Ser Ser Glu Glu Gly Leu Pro Ala Val Ser Asp
325 330 335
Glu Gln Leu Ala Arg Trp Leu Glu Thr Arg Asp Pro Ala Gln Leu Glu
340 345 350
Glu Arg Arg Lys Leu Met Met Ala Ala Val Leu Val Thr Val Glu Leu
355 360 365
Glu Cys Leu Gln Arg Phe Phe Ala Asp Pro Glu Met Gln Arg Lys Leu
370 375 380
Glu Glu Thr Leu His Tyr Thr Phe Arg Gln Gly Tyr Val Arg Gln Ala
385 390 395 400
Cys Lys Ile Ser Asn Val Glu Leu Cys Asn Leu Val Ser Tyr Leu Gly
405 410 415
Ile Leu His Glu Asn Arg Leu Gly Gln Asn Val Leu His Ser Thr Leu
420 425 430
Lys Gly Glu Ala Arg Arg Asp Tyr Ile Arg Asp Cys Ala Tyr Leu Phe
435 440 445
Leu Cys Tyr Thr Trp Gln Thr Ala Met Gly Val Trp Gln Gln Cys Leu
450 455 460
Glu Glu Arg Asn Leu Lys Glu Leu Glu Lys Leu Leu Lys Arg Thr Leu
465 470 475 480
Arg Asp Leu Trp Thr Gly Phe Asn Glu Arg Ser Val Ala Ala Ala Leu
485 490 495
Ala Asp Ile Ile Phe Pro Glu Arg Leu Leu Lys Thr Leu Gln Gln Gly
500 505 510
Leu Pro Asp Phe Thr Ser Gln Ser Met Leu Gln Asn Phe Arg Thr Phe
515 520 525
Ile Leu Glu Arg Ser Gly Ile Leu Pro Ala Thr Cys Cys Ala Leu Pro
530 535 540
Ser Asp Phe Val Pro Ile Lys Tyr Arg Glu Cys Pro Pro Pro Leu Trp
545 550 555 560
Gly His Cys Tyr Leu Phe Gln Leu Ala Asn Tyr Leu Ala Tyr His Ser
565 570 575
Asp Leu Met Glu Asp Val Ser Gly Glu Gly Leu Leu Glu Cys His Cys
580 585 590
Arg Cys Asn Leu Cys Thr Pro His Arg Ser Leu Val Cys Asn Pro Gln
595 600 605
Leu Leu Ser Glu Ser Gln Ile Ile Gly Thr Phe Glu Leu Gln Gly Pro
610 615 620
Ser Pro Asp Glu Lys Ser Ala Ala Pro Gly Leu Lys Leu Thr Pro Gly
625 630 635 640
Leu Trp Thr Ser Ala Tyr Leu Arg Lys Phe Val Pro Glu Asp Tyr His
645 650 655
Ala His Glu Ile Arg Phe Tyr Glu Asp Gln Ser Arg Pro Pro Lys Ala
660 665 670
Glu Leu Thr Ala Cys Val Ile Thr Gln Gly His Ile Leu Gly Gln Leu
675 680 685
Gln Ala Ile Asn Lys Ala Arg Arg Glu Phe Leu Leu Lys Lys Gly Arg
690 695 700
Gly Val Tyr Leu Asp Pro Gln Ser Gly Glu Glu Leu Asn Pro Leu Pro
705 710 715 720
Pro Pro Pro Pro Gln Gln Arg Asp Leu Ala Ser Gln Asp Gly Thr Gln
725 730 735
Lys Glu Ala Ala Ala Ala Ala Ala Ala Ile His Ala Ser Gly Gly Arg
740 745 750
Gly Gly Gly Leu Gly Gln Ser Gly Arg Gly Gly Phe Gly Arg Gly Ala
755 760 765
Gly Gly Asp Asp Gly Arg Leu Gly Gly Gly Gln Gln Pro Arg Arg Gly
770 775 780
Ser Phe Arg Gly Arg Arg Gly Gly Arg Arg Asn Thr Ile Thr Leu Gly
785 790 795 800
Arg Ser Pro Leu Ala Gly Ala Pro Glu Ile Leu Arg Thr Gln His Gln
805 810 815
Arg Tyr Asn Leu Arg Ser Ser Gly Ala Gly Ala Thr Arg Pro Gln Thr
820 825 830
Gln Pro
<210> 14
<211> 227
<212> PRT
<213> Simian adenovirus 40
<400> 14
Met Ser Lys Glu Ile Pro Thr Pro Tyr Met Trp Ser Tyr Gln Pro Gln
1 5 10 15
Met Gly Leu Ala Ala Gly Ala Ala Gln Asp Tyr Ser Thr Arg Met Asn
20 25 30
Tyr Met Ser Ala Gly Pro His Met Ile Ser Gln Val Asn Gly Ile Arg
35 40 45
Ala Gln Arg Asn Gln Ile Leu Leu Glu Gln Ala Ala Ile Thr Ala Thr
50 55 60
Pro Arg His Asn Leu Asn Pro Arg Asn Trp Pro Ala Ala Leu Val Tyr
65 70 75 80
Gln Glu Thr Pro Ser Ala Thr Thr Val Leu Leu Pro Arg Asp Ala Gln
85 90 95
Ala Glu Val Gln Met Thr Asn Ser Gly Ala Gln Leu Ala Gly Gly Phe
100 105 110
Arg His Gly Ala Arg Pro Leu Arg Pro Gly Ile Arg His Leu Met Ile
115 120 125
Arg Gly Arg Gly Ile Gln Leu Asn Asp Glu Ser Val Ser Ser Ser Leu
130 135 140
Gly Leu Arg Pro Asp Gly Thr Phe Gln Leu Ala Gly Ser Gly Arg Ser
145 150 155 160
Ser Phe Thr Pro Arg Gln Ala Tyr Leu Thr Leu Gln Thr Ser Ser Ser
165 170 175
Glu Pro Arg Ser Gly Gly Ile Gly Thr Leu Gln Phe Val Glu Glu Phe
180 185 190
Val Pro Ser Val Tyr Phe Asn Pro Phe Ser Gly Pro Pro Gly Arg Tyr
195 200 205
Pro Asp Gln Phe Ile Pro Asn Phe Asp Ala Val Lys Asp Ser Ala Asp
210 215 220
Gly Tyr Asp
225
<210> 15
<211> 105
<212> PRT
<213> Simian adenovirus 40
<400> 15
Met Ser Gly Ala Glu Ala Glu Gln Leu Arg Leu Arg His Leu Glu His
1 5 10 15
Cys Arg Arg His Lys Cys Phe Ala Arg Gly Ser Gly Glu Phe Cys Tyr
20 25 30
Phe Gln Leu Pro Glu Glu His Thr Glu Gly Pro Ala His Gly Val Arg
35 40 45
Leu Thr Thr Gln Gly Glu Val Thr Cys Ser Leu Ile Arg Glu Phe Thr
50 55 60
Leu Arg Pro Leu Leu Val Glu Arg Glu Arg Gly Pro Cys Val Leu Thr
65 70 75 80
Ile Ala Cys Asn Cys Pro Asn Pro Gly Leu His Gln Asp Leu Cys Cys
85 90 95
His Leu Cys Ala Glu Phe Asn Lys Arg
100 105
<210> 16
<211> 165
<212> PRT
<213> Simian adenovirus 40
<400> 16
Met Asn Arg Tyr Met Val Leu Ser Ile Leu Gly Leu Leu Ala Leu Ala
1 5 10 15
Ala Cys Ser Ala Ala Lys Lys Glu Ile Thr Phe Glu Glu Pro Ala Cys
20 25 30
Asn Val Thr Phe Lys Pro Glu Gly Asp Gln Cys Thr Thr Leu Val Lys
35 40 45
Cys Val Thr Asn His Glu Arg Leu Arg Ile Asp Tyr Lys Asn Lys Thr
50 55 60
Gly Arg Phe Ala Val Tyr Ser Val Phe Thr Pro Gly Asp Pro Ser Asn
65 70 75 80
Tyr Ser Val Thr Val Phe Gln Gly Gly Gln Ser Lys Ile Phe Asn Tyr
85 90 95
Thr Phe Pro Phe Tyr Glu Leu Cys Asp Ala Val Met Tyr Met Ser Lys
100 105 110
Gln Tyr Asn Leu Trp Pro Pro Ser Pro Gln Ala Cys Val Glu Asn Thr
115 120 125
Gly Ser Tyr Cys Cys Met Ala Phe Ala Ile Thr Thr Leu Ala Leu Ile
130 135 140
Cys Thr Val Leu Tyr Ile Lys Phe Arg Gln Arg Arg Ile Phe Ile Asp
145 150 155 160
Glu Lys Lys Met Pro
165
<210> 17
<211> 298
<212> PRT
<213> Simian adenovirus 40
<400> 17
Met Asn Ala Ile Thr Ser Leu Leu Ile Thr Thr Thr Leu Leu Ala Ile
1 5 10 15
Ala His Gly Leu Thr Arg Ile Glu Val Pro Val Gly Ser Asn Val Thr
20 25 30
Met Val Gly Pro Ala Gly Asn Ser Thr Leu Met Trp Glu Lys Phe Val
35 40 45
Arg Asn Gln Trp Val His Phe Cys Ser Asn Arg Ile Ser Ile Lys Pro
50 55 60
Arg Ala Ile Cys Asp Gly Gln Asn Leu Thr Leu Ile Asn Val Gln Met
65 70 75 80
Met Asp Ala Gly Tyr Tyr Tyr Gly Gln Arg Gly Glu Ile Ile Asn Tyr
85 90 95
Trp Arg Pro His Lys Asp Tyr Met Leu His Val Val Glu Ala Leu Pro
100 105 110
Thr Thr Thr Pro Thr Thr Thr Ser Pro Thr Thr Thr Thr Thr Thr Thr
115 120 125
Thr Thr Thr Thr Thr Thr Thr Thr Ala Ala Arg His Thr Arg Lys Ser
130 135 140
Thr Met Ile Ser Thr Lys Pro Pro Arg Ala His Ser His Ala Gly Gly
145 150 155 160
Pro Ile Gly Ala Thr Ser Glu Thr Thr Glu Leu Cys Phe Cys Gln Cys
165 170 175
Thr Asn Ala Ser Ala His Glu Leu Phe Asp Leu Glu Asn Glu Asp Ala
180 185 190
Gln Gln Ser Ser Ala Cys Leu Thr Gln Glu Ala Val Glu Pro Val Ala
195 200 205
Leu Lys Gln Ile Gly Asp Ser Ile Ile Asp Ser Ser Ser Phe Ala Thr
210 215 220
Pro Glu Tyr Pro Pro Asp Ser Thr Phe His Ile Thr Gly Thr Lys Asp
225 230 235 240
Pro Asn Leu Ser Phe Tyr Leu Met Leu Leu Leu Cys Ile Ser Val Val
245 250 255
Ser Ser Ala Leu Met Leu Leu Gly Met Phe Cys Cys Leu Ile Cys Arg
260 265 270
Arg Lys Arg Lys Ala Arg Ser Gln Gly Gln Pro Leu Met Pro Phe Pro
275 280 285
Tyr Pro Pro Asp Phe Ala Asp Asn Lys Ile
290 295
<210> 18
<211> 90
<212> PRT
<213> Simian adenovirus 40
<400> 18
Met Pro Arg Ile Phe Leu Tyr Met Phe Leu Leu Pro Pro Phe Leu Gly
1 5 10 15
Cys Ser Thr Leu Ala Ala Val Ser His Leu Glu Val Asp Cys Leu Ser
20 25 30
Pro Phe Thr Val Tyr Leu Leu Tyr Gly Leu Val Thr Leu Thr Leu Ile
35 40 45
Cys Ser Leu Ile Thr Val Ile Ile Ala Phe Ile Gln Cys Ile Asp Tyr
50 55 60
Ile Cys Val Arg Leu Ala Tyr Phe Arg His His Pro Gln Tyr Arg Asp
65 70 75 80
Arg Asn Ile Ala Gln Leu Leu Arg Leu Leu
85 90
<210> 19
<211> 132
<212> PRT
<213> Simian adenovirus 40
<400> 19
Met His Lys Thr Val Ile Cys Leu Leu Ile Leu Cys Ile Leu Pro Thr
1 5 10 15
Leu Thr Ser Cys Gln Tyr Thr Thr Lys Ser Pro Arg Lys Arg His Ala
20 25 30
Ser Cys Arg Phe Thr Gln Leu Trp Asn Ile Pro Lys Cys Tyr Asn Glu
35 40 45
Lys Ser Glu Leu Ser Glu Ala Trp Leu Tyr Gly Val Ile Cys Val Leu
50 55 60
Val Phe Cys Ser Thr Val Phe Ala Leu Met Ile Tyr Pro Tyr Phe Asp
65 70 75 80
Leu Gly Trp Asn Ala Ile Asp Ala Met Asn Tyr Pro Thr Phe Pro Ala
85 90 95
Pro Glu Ile Ile Pro Leu Arg Gln Val Val Pro Val Val Val Asn Gln
100 105 110
Arg Pro Pro Ser Pro Thr Pro Thr Glu Ile Ser Tyr Phe Asn Leu Thr
115 120 125
Gly Gly Asp Asp
130
<210> 20
<211> 543
<212> PRT
<213> Simian adenovirus 40
<400> 20
Met Lys Arg Thr Lys Thr Ser Asp Glu Ser Phe Asn Pro Val Tyr Pro
1 5 10 15
Tyr Asp Thr Glu Ser Gly Pro Pro Ser Val Pro Phe Leu Thr Pro Pro
20 25 30
Phe Val Ser Pro Asp Gly Phe Gln Glu Ser Pro Pro Gly Val Leu Ser
35 40 45
Leu Asn Leu Ala Glu Pro Leu Val Thr Ser His Gly Met Leu Ala Leu
50 55 60
Lys Met Gly Ser Gly Leu Ser Leu Asp Asp Ala Gly Asn Leu Thr Ser
65 70 75 80
Gln Asp Ile Thr Ser Thr Thr Pro Pro Leu Lys Lys Thr Lys Thr Asn
85 90 95
Leu Ser Leu Glu Thr Ser Ser Pro Leu Thr Val Ser Thr Ser Gly Ala
100 105 110
Leu Thr Val Ala Ala Ala Ala Pro Leu Ala Val Ala Gly Thr Ser Leu
115 120 125
Thr Met Gln Ser Glu Ala Pro Leu Ala Val Gln Asp Ala Lys Leu Thr
130 135 140
Leu Ala Thr Lys Gly Pro Leu Thr Val Ser Glu Gly Lys Leu Ala Leu
145 150 155 160
Gln Thr Ser Ala Pro Leu Thr Ala Ala Asp Ser Ser Thr Leu Thr Val
165 170 175
Ser Ser Thr Pro Pro Ile Ser Val Ser Ser Gly Ser Leu Gly Leu Asp
180 185 190
Met Glu Asp Pro Met Tyr Thr His Asp Gly Lys Leu Gly Ile Arg Ile
195 200 205
Gly Gly Pro Leu Arg Val Val Asp Ser Leu His Thr Leu Thr Val Val
210 215 220
Thr Gly Asn Gly Leu Thr Val Asp Asn Asn Ala Leu Gln Thr Arg Val
225 230 235 240
Thr Gly Ala Leu Gly Tyr Asp Thr Ser Gly Asn Leu Gln Leu Arg Ala
245 250 255
Ala Gly Gly Met Arg Ile Asp Ala Asn Gly Gln Leu Ile Leu Asp Val
260 265 270
Ala Tyr Pro Phe Asp Ala Gln Asn Asn Leu Ser Leu Arg Leu Gly Gln
275 280 285
Gly Pro Leu Tyr Val Asn Thr Asp His Asn Leu Asp Leu Asn Cys Asn
290 295 300
Arg Gly Leu Thr Thr Thr Thr Thr Asn Asn Thr Lys Lys Leu Glu Thr
305 310 315 320
Lys Ile Ser Ser Gly Leu Asp Tyr Asp Thr Asn Gly Ala Val Ile Ile
325 330 335
Lys Leu Gly Thr Gly Leu Ser Phe Asp Asn Thr Gly Ala Leu Thr Val
340 345 350
Gly Asn Thr Gly Asp Asp Lys Leu Thr Leu Trp Thr Thr Pro Asp Pro
355 360 365
Ser Pro Asn Cys Arg Ile His Ser Asp Lys Asp Cys Lys Phe Thr Leu
370 375 380
Val Leu Thr Lys Cys Gly Ser Gln Ile Leu Ala Ser Val Ala Ala Leu
385 390 395 400
Ala Val Ser Gly Asn Leu Ala Ser Ile Thr Gly Thr Val Ala Ser Val
405 410 415
Thr Ile Phe Leu Arg Phe Asp Gln Asn Gly Val Leu Met Glu Asn Ser
420 425 430
Ser Leu Asp Lys Gln Tyr Trp Asn Phe Arg Asn Gly Asn Ser Thr Asn
435 440 445
Ala Ala Pro Tyr Thr Asn Ala Val Gly Phe Met Pro Asn Leu Ala Ala
450 455 460
Tyr Pro Lys Thr Gln Ser Gln Thr Ala Lys Asn Asn Ile Val Ser Gln
465 470 475 480
Val Tyr Leu Asn Gly Asp Lys Ser Lys Pro Met Thr Leu Thr Ile Thr
485 490 495
Leu Asn Gly Thr Asn Glu Ser Ser Glu Thr Ser Gln Val Ser His Tyr
500 505 510
Ser Met Ser Phe Thr Trp Ala Trp Glu Ser Gly Gln Tyr Ala Thr Glu
515 520 525
Thr Phe Ala Thr Asn Ser Phe Thr Phe Ser Tyr Ile Ala Glu Gln
530 535 540
<210> 21
<211> 640
<212> DNA
<213> Simian adenovirus 40
<220>
<221> CDS
<222> (1)..(636)
<223> label=Elb\19K
<400> 21
atg gtg tgt tta act tgg gcg gag tct gct ggg tat ata agc ttc cct 48
Met Val Cys Leu Thr Trp Ala Glu Ser Ala Gly Tyr Ile Ser Phe Pro
1 5 10 15
ggg cta aac ttg gtt aca ctt gac ctc atg gag gcc tgg gag tgt ttg 96
Gly Leu Asn Leu Val Thr Leu Asp Leu Met Glu Ala Trp Glu Cys Leu
20 25 30
gag aac ttt gcc gga gtt cgt gcc ttg ctg gac gag agc tct aac aat 144
Glu Asn Phe Ala Gly Val Arg Ala Leu Leu Asp Glu Ser Ser Asn Asn
35 40 45
acc tct tgg tgg tgg agg tat ttg tgg ggc tct ccc cag ggc aag tta 192
Thr Ser Trp Trp Trp Arg Tyr Leu Trp Gly Ser Pro Gln Gly Lys Leu
50 55 60
gtt tgt aga atc aag gag gat tac aag tgg gaa ttt gaa gag ctt ttg 240
Val Cys Arg Ile Lys Glu Asp Tyr Lys Trp Glu Phe Glu Glu Leu Leu
65 70 75 80
aaa tcc tgt ggt gag cta ttg gat tct ttg aat cta ggc cac cag gct 288
Lys Ser Cys Gly Glu Leu Leu Asp Ser Leu Asn Leu Gly His Gln Ala
85 90 95
ctc ttc cag gag aag gtc atc agg act ttg gat ttt tcc aca ccg ggg 336
Leu Phe Gln Glu Lys Val Ile Arg Thr Leu Asp Phe Ser Thr Pro Gly
100 105 110
cgc att gca gcc gcg gtt gct ttt cta gct ttt ttg aag gat aga tgg 384
Arg Ile Ala Ala Ala Val Ala Phe Leu Ala Phe Leu Lys Asp Arg Trp
115 120 125
agc gaa gag acc cac ttg agt tcg ggc tac gtc ctg gat ttt ctg gcc 432
Ser Glu Glu Thr His Leu Ser Ser Gly Tyr Val Leu Asp Phe Leu Ala
130 135 140
atg caa ctg tgg aga gca tgg atc aga cac aag aac agg ctg caa ctg 480
Met Gln Leu Trp Arg Ala Trp Ile Arg His Lys Asn Arg Leu Gln Leu
145 150 155 160
ttg tct tcc gtc cgc ccg ttg ctg att ccg gcg gag gag caa cag gcc 528
Leu Ser Ser Val Arg Pro Leu Leu Ile Pro Ala Glu Glu Gln Gln Ala
165 170 175
ggg tca gag gac cgg gcc cgt cgg gat ccg gag gag agg gca ccg agg 576
Gly Ser Glu Asp Arg Ala Arg Arg Asp Pro Glu Glu Arg Ala Pro Arg
180 185 190
ccg ggc gag agg agc gcg ctg aac ctg gga acc ggg ctg agc ggc cat 624
Pro Gly Glu Arg Ser Ala Leu Asn Leu Gly Thr Gly Leu Ser Gly His
195 200 205
cca cat cgg gag tgaa 640
Pro His Arg Glu
210
<210> 22
<211> 212
<212> PRT
<213> Simian adenovirus 40
<400> 22
Met Val Cys Leu Thr Trp Ala Glu Ser Ala Gly Tyr Ile Ser Phe Pro
1 5 10 15
Gly Leu Asn Leu Val Thr Leu Asp Leu Met Glu Ala Trp Glu Cys Leu
20 25 30
Glu Asn Phe Ala Gly Val Arg Ala Leu Leu Asp Glu Ser Ser Asn Asn
35 40 45
Thr Ser Trp Trp Trp Arg Tyr Leu Trp Gly Ser Pro Gln Gly Lys Leu
50 55 60
Val Cys Arg Ile Lys Glu Asp Tyr Lys Trp Glu Phe Glu Glu Leu Leu
65 70 75 80
Lys Ser Cys Gly Glu Leu Leu Asp Ser Leu Asn Leu Gly His Gln Ala
85 90 95
Leu Phe Gln Glu Lys Val Ile Arg Thr Leu Asp Phe Ser Thr Pro Gly
100 105 110
Arg Ile Ala Ala Ala Val Ala Phe Leu Ala Phe Leu Lys Asp Arg Trp
115 120 125
Ser Glu Glu Thr His Leu Ser Ser Gly Tyr Val Leu Asp Phe Leu Ala
130 135 140
Met Gln Leu Trp Arg Ala Trp Ile Arg His Lys Asn Arg Leu Gln Leu
145 150 155 160
Leu Ser Ser Val Arg Pro Leu Leu Ile Pro Ala Glu Glu Gln Gln Ala
165 170 175
Gly Ser Glu Asp Arg Ala Arg Arg Asp Pro Glu Glu Arg Ala Pro Arg
180 185 190
Pro Gly Glu Arg Ser Ala Leu Asn Leu Gly Thr Gly Leu Ser Gly His
195 200 205
Pro His Arg Glu
210
<210> 23
<211> 6020
<212> DNA
<213> Simian adenovirus 40
<220>
<221> CDS
<222> (1)..(597)
<223> label=22K
<220>
<221> CDS
<222> (1976)..(2515)
<223> label=E3\CR1\alpha
<220>
<221> CDS
<222> (4112)..(4951)
<223> label=E3\CR1\gamma
<220>
<221> CDS
<222> (5632)..(6015)
<223> label=E3\14.7K
<400> 23
atg gca ccc aga aag aag cag cag ccg ccg ccg cag cca tac atg ctt 48
Met Ala Pro Arg Lys Lys Gln Gln Pro Pro Pro Gln Pro Tyr Met Leu
1 5 10 15
ctg gag gaa gag gag gag gac tgg gac agt cag gca gag gag gtt tcg 96
Leu Glu Glu Glu Glu Glu Asp Trp Asp Ser Gln Ala Glu Glu Val Ser
20 25 30
gac gag gag cag gag gag atg atg gaa gac tgg gag gag gac agc agc 144
Asp Glu Glu Gln Glu Glu Met Met Glu Asp Trp Glu Glu Asp Ser Ser
35 40 45
cta gac gag gaa gct tca gag gcc gaa gag gtg gca gac gca aca cca 192
Leu Asp Glu Glu Ala Ser Glu Ala Glu Glu Val Ala Asp Ala Thr Pro
50 55 60
tca ccc tcg gtc gca gcc ccc tcg ccg ggg ccc ctg aaa tcc tcc gaa 240
Ser Pro Ser Val Ala Ala Pro Ser Pro Gly Pro Leu Lys Ser Ser Glu
65 70 75 80
ccc agc acc agc gct ata acc tcc gct cct ccg gcg ccg gcg cca ccc 288
Pro Ser Thr Ser Ala Ile Thr Ser Ala Pro Pro Ala Pro Ala Pro Pro
85 90 95
gcc cgc aga ccc aac cgt aga tgg gac acc aca gga acc ggg gtc ggt 336
Ala Arg Arg Pro Asn Arg Arg Trp Asp Thr Thr Gly Thr Gly Val Gly
100 105 110
aag tcc aag tgc ccg ccg ccg cca ccg cag cag cag cag cag cag cgc 384
Lys Ser Lys Cys Pro Pro Pro Pro Pro Gln Gln Gln Gln Gln Gln Arg
115 120 125
cag ggc tac cgc tcg tgg cgc ggg cac aag aac gcc ata gtc gcc tgc 432
Gln Gly Tyr Arg Ser Trp Arg Gly His Lys Asn Ala Ile Val Ala Cys
130 135 140
ttg caa gac tgc ggg ggc aac atc tct ttc gcc cgc cgc ttc ctg cta 480
Leu Gln Asp Cys Gly Gly Asn Ile Ser Phe Ala Arg Arg Phe Leu Leu
145 150 155 160
ttc cac cac ggg gtc gcc ttt ccc cgc aat gtc ctg cat tac tac cgt 528
Phe His His Gly Val Ala Phe Pro Arg Asn Val Leu His Tyr Tyr Arg
165 170 175
cat ctc tac agc ccc tac tgc agc ggc gac cca gag gcg gca gcg gca 576
His Leu Tyr Ser Pro Tyr Cys Ser Gly Asp Pro Glu Ala Ala Ala Ala
180 185 190
gcc aca gcg gcg acc acc acc taggaagata tcctccgcgg gcaagacagc 627
Ala Thr Ala Ala Thr Thr Thr
195
ggcagcagcg gccaggagac ccgcggcggc agcggcggga gcggtgggcg ctctgcgcct 687
ctcgcccaac gaacccctct cgacccggga gctcagacac aggatcttcc ccactttgta 747
tgccatcttc caacagagca gaggccagga gcaggagctg aaaataaaaa acagatctct 807
gcgctccctc acccgcagct gtctgtatca caaaagcgaa gatcagcttc ggcgcacgct 867
ggaggacgcg gaggcactct tcagcaaata ctgcgcgctc actcttaaag actagctccg 927
cgcccttctc gaatttaggc gggagaaaac tacgtcatcg ccggccgccg cccagcccgc 987
ccagccgaga tgagcaaaga gattcccacg ccatacatgt ggagctacca gccgcagatg 1047
ggactcgcgg cgggagcggc ccaggactac tccacccgca tgaactacat gagcgcggga 1107
ccccacatga tctcacaggt caacgggatc cgcgcccagc gaaaccaaat actgctggaa 1167
caggcggcca tcaccgccac gccccgccat aatctcaacc cccgaaattg gcccgccgcc 1227
ctcgtgtacc aggaaacccc ctccgccacc accgtactac ttccgcgtga cgcccaggcc 1287
gaagtccaga tgactaactc aggggcgcag ctcgcgggcg gctttcgtca cggggcgcgg 1347
ccgctccgac caggtataag acacctgatg atcagaggcc gaggtatcca gctcaacgac 1407
gagtcggtga gctcttcgct cggtctccgt ccggacggaa ctttccagct cgccggatcc 1467
ggccgctctt cgttcacgcc ccgccaggcg taccttactc tgcagacctc gtcctcggag 1527
ccccgctccg gcggcatcgg aaccctccag ttcgtggagg agttcgtgcc ctcggtctac 1587
ttcaacccct tctcgggacc tcccggacgc taccccgacc agttcattcc gaactttgac 1647
gcggtgaagg actcggcgga cggctacgac tgaatgtcag gtgccgaggc agagcagctt 1707
cgcctgagac acctcgagca ctgccgccgc cacaagtgct tcgcccgcgg ttccggtgag 1767
ttctgctact ttcagctacc cgaggagcat accgaggggc cggcgcacgg cgtccgcctg 1827
accacccagg gcgaggttac ctgttccctc atccgggagt tcaccctccg tcccctgcta 1887
gtggagcggg agcggggtcc ctgtgtccta actatcgcct gcaactgccc taaccctgga 1947
ttacatcaag atctttgctg tcatctct gtg ctg agt tta ata aac gct gag 1999
Val Leu Ser Leu Ile Asn Ala Glu
200 205
atc aga atc tac tgg ggc tcc tgt cgc cat cct gtg aac gcc acc gtc 2047
Ile Arg Ile Tyr Trp Gly Ser Cys Arg His Pro Val Asn Ala Thr Val
210 215 220
ttc acc cac ccc gac cag gcc cag gcg aac ctc acc tgc ggt ctg cat 2095
Phe Thr His Pro Asp Gln Ala Gln Ala Asn Leu Thr Cys Gly Leu His
225 230 235
cgg agg gcc aag aag tac ctc acc tgg tac ttc aac ggc acc ccc ttt 2143
Arg Arg Ala Lys Lys Tyr Leu Thr Trp Tyr Phe Asn Gly Thr Pro Phe
240 245 250 255
gtg gtt tac aac agc ttc gac ggg gac gga gtc tcc ctg aaa gac cag 2191
Val Val Tyr Asn Ser Phe Asp Gly Asp Gly Val Ser Leu Lys Asp Gln
260 265 270
ctc tcc ggt ctc agc tac tcc atc cac aag aac acc acc ctc caa ctc 2239
Leu Ser Gly Leu Ser Tyr Ser Ile His Lys Asn Thr Thr Leu Gln Leu
275 280 285
ttc cct ccc tac ctg ccg gga acc tac gag tgc gtc acc ggc cgc tgc 2287
Phe Pro Pro Tyr Leu Pro Gly Thr Tyr Glu Cys Val Thr Gly Arg Cys
290 295 300
acc cac ctc acc cgc ctg atc gta aac cag agc ttt ccg gga aca gat 2335
Thr His Leu Thr Arg Leu Ile Val Asn Gln Ser Phe Pro Gly Thr Asp
305 310 315
aac tct ctc ttc ccc aga aca gga ggt gag ctc agg aaa ctc ccc ggg 2383
Asn Ser Leu Phe Pro Arg Thr Gly Gly Glu Leu Arg Lys Leu Pro Gly
320 325 330 335
gac cag ggc gga gac gta cct tcg acc ctt gtg ggg tta gga ttt ttt 2431
Asp Gln Gly Gly Asp Val Pro Ser Thr Leu Val Gly Leu Gly Phe Phe
340 345 350
att acc ggg ttg ctg gct ctt tta atc aaa gct tcc ttg aga ttt gtt 2479
Ile Thr Gly Leu Leu Ala Leu Leu Ile Lys Ala Ser Leu Arg Phe Val
355 360 365
ctt tcc ttc tac gtg tat gaa cac ctc aac ctc caa taactctacc 2525
Leu Ser Phe Tyr Val Tyr Glu His Leu Asn Leu Gln
370 375
ctttcttcgg aatcaggtga cttctctgaa atcgggcttg gtgtgctgct tactctgttg 2585
atttttttcc ttatcatact cagccttctg tgcctcaggc tcgccgcctg ctgcgcacac 2645
atctatatct actgctggtt gctcaagtgc aggggtcgcc acccaagatg aacaggtaca 2705
tggtcctatc gatcctaggc ctgctggccc tggcggcctg cagcgccgcc aaaaaagaga 2765
ttacctttga ggagcccgct tgcaatgtaa ctttcaagcc cgagggtgac caatgcacca 2825
ccctcgtcaa atgcgttacc aatcatgaga ggctgcgcat cgactacaaa aacaaaactg 2885
gccggtttgc ggtctatagt gtgtttacgc ccggagaccc ctctaactac tctgtcaccg 2945
tcttccaggg cggacagtct aagatattca attacacttt ccctttttat gagttgtgcg 3005
atgcggtcat gtacatgtca aaacagtaca acctgtggcc tccctctccc caggcgtgtg 3065
tggaaaatac tgggtcttac tgctgtatgg ctttcgcaat cactacgctc gctctaatct 3125
gcacggtgct atatataaaa ttcaggcaga ggcgaatctt tatcgatgaa aagaaaatgc 3185
cttgatcgct aacaccggct ttctatctgc agaatgaatg caatcacctc cctactaatc 3245
accaccaccc tccttgcgat tgcccatggg ttgacacgaa tcgaagtgcc agtggggtcc 3305
aatgtcacca tggtgggccc cgccggcaat tccaccctca tgtgggaaaa atttgtccgc 3365
aatcaatggg ttcatttctg ctctaaccga atcagtatca agcccagagc catctgcgat 3425
gggcaaaatc taactctgat caatgtgcaa atgatggatg ctgggtacta ttacgggcag 3485
cggggagaaa tcattaatta ctggcgaccc cacaaggact acatgctgca tgtagtcgag 3545
gcacttccca ctaccacccc cactaccacc tctcccacca ccactaccac caccactact 3605
actactacta ctaccactac cgctgcccgc catacccgca aaagcaccat gattagcaca 3665
aagccccctc gtgctcactc ccacgccggc gggcccatcg gtgcgacctc agaaaccacc 3725
gagctttgct tctgccaatg cactaacgcc agcgctcatg aactgttcga cctggagaat 3785
gaggatgccc agcagagctc cgcttgcctg acccaggagg ctgtggagcc cgttgccctg 3845
aagcagatcg gtgattcaat aattgactct tcttcttttg ccactcccga ataccctccc 3905
gattctactt tccacatcac gggtaccaaa gaccctaacc tctctttcta cctgatgctg 3965
ctgctctgta tctctgtggt ctcttccgcg ctgatgttac tggggatgtt ctgctgcctg 4025
atctgccgca gaaagagaaa agctcgctct cagggccaac cactgatgcc cttcccctac 4085
cccccggatt ttgcagataa caagat atg agc tcg ctg ctg aca cta acc gct 4138
Met Ser Ser Leu Leu Thr Leu Thr Ala
380 385
tta cta gcc tgc gct cta acc ctt gtc gct tgc gac tcg aga ttc cac 4186
Leu Leu Ala Cys Ala Leu Thr Leu Val Ala Cys Asp Ser Arg Phe His
390 395 400
aat gtc aca gct gtg gca gga gaa aat gtt act ttc aac tcc acg gcc 4234
Asn Val Thr Ala Val Ala Gly Glu Asn Val Thr Phe Asn Ser Thr Ala
405 410 415 420
gat acc cag tgg tcg tgg agt ggc tca ggt agc tac tta act atc tgc 4282
Asp Thr Gln Trp Ser Trp Ser Gly Ser Gly Ser Tyr Leu Thr Ile Cys
425 430 435
aat agc tcc act tcc ccc agc ata tcc cca acc aag tac caa tgc aat 4330
Asn Ser Ser Thr Ser Pro Ser Ile Ser Pro Thr Lys Tyr Gln Cys Asn
440 445 450
gcc agc ctg ttc acc ctc atc aac gct tcc acc ctg gac aat gga ctc 4378
Ala Ser Leu Phe Thr Leu Ile Asn Ala Ser Thr Leu Asp Asn Gly Leu
455 460 465
tat gta ggc tat gta ccc ttt ggt ggg caa gga aag acc cac gct tac 4426
Tyr Val Gly Tyr Val Pro Phe Gly Gly Gln Gly Lys Thr His Ala Tyr
470 475 480
aac ctg gaa gtt cgc cag ccc aga acc act acc caa gct tct ccc acc 4474
Asn Leu Glu Val Arg Gln Pro Arg Thr Thr Thr Gln Ala Ser Pro Thr
485 490 495 500
acc acc acc acc atc agc agc agc agc agc agc agc cac agc agc agc 4522
Thr Thr Thr Thr Ile Ser Ser Ser Ser Ser Ser Ser His Ser Ser Ser
505 510 515
agc aga tta ttg act ttg gtt ttg gcc agc tca tct gcc gct acc cag 4570
Ser Arg Leu Leu Thr Leu Val Leu Ala Ser Ser Ser Ala Ala Thr Gln
520 525 530
gcc atc tac agc tct gtg ccc gaa acc act cag atc cac cgc cca gaa 4618
Ala Ile Tyr Ser Ser Val Pro Glu Thr Thr Gln Ile His Arg Pro Glu
535 540 545
acg acc acc gcc acc acc cta cac acc tcc agc gat cag atg ccg acc 4666
Thr Thr Thr Ala Thr Thr Leu His Thr Ser Ser Asp Gln Met Pro Thr
550 555 560
aac atc acc ccc ttg gct ctt caa atg gga ctt aca agc ccc act cca 4714
Asn Ile Thr Pro Leu Ala Leu Gln Met Gly Leu Thr Ser Pro Thr Pro
565 570 575 580
aaa cca gtg gat gcg acc gag gtc tcc gcc ctc gtc aat gac tgg gcg 4762
Lys Pro Val Asp Ala Thr Glu Val Ser Ala Leu Val Asn Asp Trp Ala
585 590 595
ggg ctg gga atg tgg tgg ttc gcc ata ggc atg atg gcg ctc tgc ctg 4810
Gly Leu Gly Met Trp Trp Phe Ala Ile Gly Met Met Ala Leu Cys Leu
600 605 610
ctt ctg ctc tgg ctc atc tgc tgc ctc cac cgc agg cga gcc aga ccc 4858
Leu Leu Leu Trp Leu Ile Cys Cys Leu His Arg Arg Arg Ala Arg Pro
615 620 625
ccc atc tat aga ccc atc att gtc ctg aac ccc gat aat gat ggg atc 4906
Pro Ile Tyr Arg Pro Ile Ile Val Leu Asn Pro Asp Asn Asp Gly Ile
630 635 640
cat aga ttg gat ggc ctg aaa aac cta ctt ttt tct ttt aca gta 4951
His Arg Leu Asp Gly Leu Lys Asn Leu Leu Phe Ser Phe Thr Val
645 650 655
tgataaattg agacatgcct cgcattttct tgtacatgtt ccttctccca ccttttctgg 5011
ggtgttctac gctggccgct gtgtctcacc tggaggtaga ctgcctctca cccttcactg 5071
tctacctgct ttacggattg gtcaccctca ctctcatctg cagcctaatc acagtaatca 5131
tcgccttcat ccagtgcatt gattacatct gtgtgcgcct cgcatacttc agacaccacc 5191
cgcagtaccg agacaggaac attgcccaac ttctaagact gctctaatca tgcataagac 5251
tgtgatctgc cttctgatcc tctgcatcct gcccaccctc acctcctgcc agtacaccac 5311
aaaatctccg cgcaaaagac atgcctcctg ccgcttcacc caactgtgga atatacccaa 5371
atgctacaac gaaaagagcg agctctccga agcttggctg tatggggtca tctgtgtctt 5431
agttttctgc agcactgtct ttgccctcat gatctacccc tactttgatt tgggatggaa 5491
cgcgatcgat gccatgaatt accccacctt tcccgcaccc gagataattc cactgcgaca 5551
agttgtgccc gttgtcgtta atcaacgccc cccatcccct acgcccactg aaatcagcta 5611
ctttaaccta acaggcggag atg act gac gcc cta gat cta gaa atg gac ggc 5664
Met Thr Asp Ala Leu Asp Leu Glu Met Asp Gly
660 665 670
atc agt acc gag cag cgt ctc cta gag agg cgc agg cag gcg gct gag 5712
Ile Ser Thr Glu Gln Arg Leu Leu Glu Arg Arg Arg Gln Ala Ala Glu
675 680 685
caa gag cgc ctc aat cag gag ctc cga gat ctc gtt aac ctg cac cag 5760
Gln Glu Arg Leu Asn Gln Glu Leu Arg Asp Leu Val Asn Leu His Gln
690 695 700
tgc aaa aga ggc atc ttt tgt ctg gta aag cag gct aaa gtc acc tac 5808
Cys Lys Arg Gly Ile Phe Cys Leu Val Lys Gln Ala Lys Val Thr Tyr
705 710 715
gag aag acc ggc aac agc cac cgc ctc agt tac aaa ttg ccc acc cag 5856
Glu Lys Thr Gly Asn Ser His Arg Leu Ser Tyr Lys Leu Pro Thr Gln
720 725 730
cgc cag aag ctg gtg ctc atg gtg ggt gag aat ccc atc acc gtc acc 5904
Arg Gln Lys Leu Val Leu Met Val Gly Glu Asn Pro Ile Thr Val Thr
735 740 745 750
cag cac tcg gta gag acc gag ggg tgt ctg cac tcc ccc tgt cgg ggt 5952
Gln His Ser Val Glu Thr Glu Gly Cys Leu His Ser Pro Cys Arg Gly
755 760 765
cca gaa gac ctc tgc acc ctg gta aag acc ctg tgc ggt ctc aga gat 6000
Pro Glu Asp Leu Cys Thr Leu Val Lys Thr Leu Cys Gly Leu Arg Asp
770 775 780
tta gtc ccc ttt aac taatc 6020
Leu Val Pro Phe Asn
785
<210> 24
<211> 199
<212> PRT
<213> Simian adenovirus 40
<400> 24
Met Ala Pro Arg Lys Lys Gln Gln Pro Pro Pro Gln Pro Tyr Met Leu
1 5 10 15
Leu Glu Glu Glu Glu Glu Asp Trp Asp Ser Gln Ala Glu Glu Val Ser
20 25 30
Asp Glu Glu Gln Glu Glu Met Met Glu Asp Trp Glu Glu Asp Ser Ser
35 40 45
Leu Asp Glu Glu Ala Ser Glu Ala Glu Glu Val Ala Asp Ala Thr Pro
50 55 60
Ser Pro Ser Val Ala Ala Pro Ser Pro Gly Pro Leu Lys Ser Ser Glu
65 70 75 80
Pro Ser Thr Ser Ala Ile Thr Ser Ala Pro Pro Ala Pro Ala Pro Pro
85 90 95
Ala Arg Arg Pro Asn Arg Arg Trp Asp Thr Thr Gly Thr Gly Val Gly
100 105 110
Lys Ser Lys Cys Pro Pro Pro Pro Pro Gln Gln Gln Gln Gln Gln Arg
115 120 125
Gln Gly Tyr Arg Ser Trp Arg Gly His Lys Asn Ala Ile Val Ala Cys
130 135 140
Leu Gln Asp Cys Gly Gly Asn Ile Ser Phe Ala Arg Arg Phe Leu Leu
145 150 155 160
Phe His His Gly Val Ala Phe Pro Arg Asn Val Leu His Tyr Tyr Arg
165 170 175
His Leu Tyr Ser Pro Tyr Cys Ser Gly Asp Pro Glu Ala Ala Ala Ala
180 185 190
Ala Thr Ala Ala Thr Thr Thr
195
<210> 25
<211> 180
<212> PRT
<213> Simian adenovirus 40
<400> 25
Val Leu Ser Leu Ile Asn Ala Glu Ile Arg Ile Tyr Trp Gly Ser Cys
1 5 10 15
Arg His Pro Val Asn Ala Thr Val Phe Thr His Pro Asp Gln Ala Gln
20 25 30
Ala Asn Leu Thr Cys Gly Leu His Arg Arg Ala Lys Lys Tyr Leu Thr
35 40 45
Trp Tyr Phe Asn Gly Thr Pro Phe Val Val Tyr Asn Ser Phe Asp Gly
50 55 60
Asp Gly Val Ser Leu Lys Asp Gln Leu Ser Gly Leu Ser Tyr Ser Ile
65 70 75 80
His Lys Asn Thr Thr Leu Gln Leu Phe Pro Pro Tyr Leu Pro Gly Thr
85 90 95
Tyr Glu Cys Val Thr Gly Arg Cys Thr His Leu Thr Arg Leu Ile Val
100 105 110
Asn Gln Ser Phe Pro Gly Thr Asp Asn Ser Leu Phe Pro Arg Thr Gly
115 120 125
Gly Glu Leu Arg Lys Leu Pro Gly Asp Gln Gly Gly Asp Val Pro Ser
130 135 140
Thr Leu Val Gly Leu Gly Phe Phe Ile Thr Gly Leu Leu Ala Leu Leu
145 150 155 160
Ile Lys Ala Ser Leu Arg Phe Val Leu Ser Phe Tyr Val Tyr Glu His
165 170 175
Leu Asn Leu Gln
180
<210> 26
<211> 280
<212> PRT
<213> Simian adenovirus 40
<400> 26
Met Ser Ser Leu Leu Thr Leu Thr Ala Leu Leu Ala Cys Ala Leu Thr
1 5 10 15
Leu Val Ala Cys Asp Ser Arg Phe His Asn Val Thr Ala Val Ala Gly
20 25 30
Glu Asn Val Thr Phe Asn Ser Thr Ala Asp Thr Gln Trp Ser Trp Ser
35 40 45
Gly Ser Gly Ser Tyr Leu Thr Ile Cys Asn Ser Ser Thr Ser Pro Ser
50 55 60
Ile Ser Pro Thr Lys Tyr Gln Cys Asn Ala Ser Leu Phe Thr Leu Ile
65 70 75 80
Asn Ala Ser Thr Leu Asp Asn Gly Leu Tyr Val Gly Tyr Val Pro Phe
85 90 95
Gly Gly Gln Gly Lys Thr His Ala Tyr Asn Leu Glu Val Arg Gln Pro
100 105 110
Arg Thr Thr Thr Gln Ala Ser Pro Thr Thr Thr Thr Thr Ile Ser Ser
115 120 125
Ser Ser Ser Ser Ser His Ser Ser Ser Ser Arg Leu Leu Thr Leu Val
130 135 140
Leu Ala Ser Ser Ser Ala Ala Thr Gln Ala Ile Tyr Ser Ser Val Pro
145 150 155 160
Glu Thr Thr Gln Ile His Arg Pro Glu Thr Thr Thr Ala Thr Thr Leu
165 170 175
His Thr Ser Ser Asp Gln Met Pro Thr Asn Ile Thr Pro Leu Ala Leu
180 185 190
Gln Met Gly Leu Thr Ser Pro Thr Pro Lys Pro Val Asp Ala Thr Glu
195 200 205
Val Ser Ala Leu Val Asn Asp Trp Ala Gly Leu Gly Met Trp Trp Phe
210 215 220
Ala Ile Gly Met Met Ala Leu Cys Leu Leu Leu Leu Trp Leu Ile Cys
225 230 235 240
Cys Leu His Arg Arg Arg Ala Arg Pro Pro Ile Tyr Arg Pro Ile Ile
245 250 255
Val Leu Asn Pro Asp Asn Asp Gly Ile His Arg Leu Asp Gly Leu Lys
260 265 270
Asn Leu Leu Phe Ser Phe Thr Val
275 280
<210> 27
<211> 128
<212> PRT
<213> Simian adenovirus 40
<400> 27
Met Thr Asp Ala Leu Asp Leu Glu Met Asp Gly Ile Ser Thr Glu Gln
1 5 10 15
Arg Leu Leu Glu Arg Arg Arg Gln Ala Ala Glu Gln Glu Arg Leu Asn
20 25 30
Gln Glu Leu Arg Asp Leu Val Asn Leu His Gln Cys Lys Arg Gly Ile
35 40 45
Phe Cys Leu Val Lys Gln Ala Lys Val Thr Tyr Glu Lys Thr Gly Asn
50 55 60
Ser His Arg Leu Ser Tyr Lys Leu Pro Thr Gln Arg Gln Lys Leu Val
65 70 75 80
Leu Met Val Gly Glu Asn Pro Ile Thr Val Thr Gln His Ser Val Glu
85 90 95
Thr Glu Gly Cys Leu His Ser Pro Cys Arg Gly Pro Glu Asp Leu Cys
100 105 110
Thr Leu Val Lys Thr Leu Cys Gly Leu Arg Asp Leu Val Pro Phe Asn
115 120 125
<210> 28
<211> 970
<212> DNA
<213> Simian adenovirus 40
<220>
<221> CDS
<222> (9)..(549)
<223> label=Ela
<220>
<221> CDS
<222> (663)..(961)
<223> label=Ela
<400> 28
gggaaaaa atg aga cat ttc acc tac gat ggc ggt gtg ctc acc ggc cag 50
Met Arg His Phe Thr Tyr Asp Gly Gly Val Leu Thr Gly Gln
1 5 10
ctg gct gct gag gtc ctg gac acc ctg atc gag gag gta ttg gct gat 98
Leu Ala Ala Glu Val Leu Asp Thr Leu Ile Glu Glu Val Leu Ala Asp
15 20 25 30
aat tat cct ccc tcg act cct ttt gag cca cct aca ctt cac gaa ctc 146
Asn Tyr Pro Pro Ser Thr Pro Phe Glu Pro Pro Thr Leu His Glu Leu
35 40 45
tac gat ctg gat gtg gtg ggg ccc agc gat ccg aac gag cag gcg gtt 194
Tyr Asp Leu Asp Val Val Gly Pro Ser Asp Pro Asn Glu Gln Ala Val
50 55 60
tcc agt ttt ttt cca gag tcc atg ttg ttg gcc agc cag gag ggg gtc 242
Ser Ser Phe Phe Pro Glu Ser Met Leu Leu Ala Ser Gln Glu Gly Val
65 70 75
gaa ctt gag acc cct cct ccg atc gtg gat tcc ccc gat ccg ccg cag 290
Glu Leu Glu Thr Pro Pro Pro Ile Val Asp Ser Pro Asp Pro Pro Gln
80 85 90
ctg act agg cag ccc gag cgc tgt gcg gga cct gag act atg ccc cag 338
Leu Thr Arg Gln Pro Glu Arg Cys Ala Gly Pro Glu Thr Met Pro Gln
95 100 105 110
ctg cta cct gag gtg atc gat ctc acc tgt aat gag tct ggt ttt cca 386
Leu Leu Pro Glu Val Ile Asp Leu Thr Cys Asn Glu Ser Gly Phe Pro
115 120 125
ccc agc gag gat gag gac gaa gag ggt gag cag ttt gtg tta gat tct 434
Pro Ser Glu Asp Glu Asp Glu Glu Gly Glu Gln Phe Val Leu Asp Ser
130 135 140
gtg gaa caa ccc ggg cga gga tgc agg tct tgt caa tat cac cgg aaa 482
Val Glu Gln Pro Gly Arg Gly Cys Arg Ser Cys Gln Tyr His Arg Lys
145 150 155
aac aca gga gac tcc cag att atg tgt tct ctg tgt tat atg aag atg 530
Asn Thr Gly Asp Ser Gln Ile Met Cys Ser Leu Cys Tyr Met Lys Met
160 165 170
acc tgt atg ttt att tac a gtaagtttat catcggtggg caggtgggct 579
Thr Cys Met Phe Ile Tyr
175 180
atagtgtggg tggtggtctt tggggggttt tttaatatat gtcaggggtt atgctgaaga 639
cttttttatt gtgattttta aag gt cca gtg tct gag ccc gag caa gaa cct 691
Ser Pro Val Ser Glu Pro Glu Gln Glu Pro
185 190
gaa ccg gag cct gag cct tct cgc ccc agg aga aag cct gta atc tta 739
Glu Pro Glu Pro Glu Pro Ser Arg Pro Arg Arg Lys Pro Val Ile Leu
195 200 205
act aga ccc agc gca ccg gta gcg aga ggc ctc agc agc gcg gag acc 787
Thr Arg Pro Ser Ala Pro Val Ala Arg Gly Leu Ser Ser Ala Glu Thr
210 215 220
acc gac tcc ggt gct tcc tca tca ccc ccg gag att cac ccc ctg gtg 835
Thr Asp Ser Gly Ala Ser Ser Ser Pro Pro Glu Ile His Pro Leu Val
225 230 235
ccc ctg tgt ccc gtt aag ccc gtt gcc gtg aga gtc agt ggg cgg cgg 883
Pro Leu Cys Pro Val Lys Pro Val Ala Val Arg Val Ser Gly Arg Arg
240 245 250
tct gct gtg gag tgc att gag gac ttg ctt ttt gat tca cag gaa cct 931
Ser Ala Val Glu Cys Ile Glu Asp Leu Leu Phe Asp Ser Gln Glu Pro
255 260 265 270
ttg gac ttg agc ttg aaa cgc ccc agg cat taaacctgg 970
Leu Asp Leu Ser Leu Lys Arg Pro Arg His
275 280
<210> 29
<211> 280
<212> PRT
<213> Simian adenovirus 40
<400> 29
Met Arg His Phe Thr Tyr Asp Gly Gly Val Leu Thr Gly Gln Leu Ala
1 5 10 15
Ala Glu Val Leu Asp Thr Leu Ile Glu Glu Val Leu Ala Asp Asn Tyr
20 25 30
Pro Pro Ser Thr Pro Phe Glu Pro Pro Thr Leu His Glu Leu Tyr Asp
35 40 45
Leu Asp Val Val Gly Pro Ser Asp Pro Asn Glu Gln Ala Val Ser Ser
50 55 60
Phe Phe Pro Glu Ser Met Leu Leu Ala Ser Gln Glu Gly Val Glu Leu
65 70 75 80
Glu Thr Pro Pro Pro Ile Val Asp Ser Pro Asp Pro Pro Gln Leu Thr
85 90 95
Arg Gln Pro Glu Arg Cys Ala Gly Pro Glu Thr Met Pro Gln Leu Leu
100 105 110
Pro Glu Val Ile Asp Leu Thr Cys Asn Glu Ser Gly Phe Pro Pro Ser
115 120 125
Glu Asp Glu Asp Glu Glu Gly Glu Gln Phe Val Leu Asp Ser Val Glu
130 135 140
Gln Pro Gly Arg Gly Cys Arg Ser Cys Gln Tyr His Arg Lys Asn Thr
145 150 155 160
Gly Asp Ser Gln Ile Met Cys Ser Leu Cys Tyr Met Lys Met Thr Cys
165 170 175
Met Phe Ile Tyr Ser Pro Val Ser Glu Pro Glu Gln Glu Pro Glu Pro
180 185 190
Glu Pro Glu Pro Ser Arg Pro Arg Arg Lys Pro Val Ile Leu Thr Arg
195 200 205
Pro Ser Ala Pro Val Ala Arg Gly Leu Ser Ser Ala Glu Thr Thr Asp
210 215 220
Ser Gly Ala Ser Ser Ser Pro Pro Glu Ile His Pro Leu Val Pro Leu
225 230 235 240
Cys Pro Val Lys Pro Val Ala Val Arg Val Ser Gly Arg Arg Ser Ala
245 250 255
Val Glu Cys Ile Glu Asp Leu Leu Phe Asp Ser Gln Glu Pro Leu Asp
260 265 270
Leu Ser Leu Lys Arg Pro Arg His
275 280
<210> 30
<211> 930
<212> DNA
<213> Simian adenovirus 40
<220>
<221> CDS
<222> (11)..(340)
<223> label=33K
<220>
<221> CDS
<222> (615)..(929)
<223> label=33K
<400> 30
gcttcccagg atg gca ccc aga aag aag cag cag ccg ccg ccg cag cca 49
Met Ala Pro Arg Lys Lys Gln Gln Pro Pro Pro Gln Pro
1 5 10
tac atg ctt ctg gag gaa gag gag gag gac tgg gac agt cag gca gag 97
Tyr Met Leu Leu Glu Glu Glu Glu Glu Asp Trp Asp Ser Gln Ala Glu
15 20 25
gag gtt tcg gac gag gag cag gag gag atg atg gaa gac tgg gag gag 145
Glu Val Ser Asp Glu Glu Gln Glu Glu Met Met Glu Asp Trp Glu Glu
30 35 40 45
gac agc agc cta gac gag gaa gct tca gag gcc gaa gag gtg gca gac 193
Asp Ser Ser Leu Asp Glu Glu Ala Ser Glu Ala Glu Glu Val Ala Asp
50 55 60
gca aca cca tca ccc tcg gtc gca gcc ccc tcg ccg ggg ccc ctg aaa 241
Ala Thr Pro Ser Pro Ser Val Ala Ala Pro Ser Pro Gly Pro Leu Lys
65 70 75
tcc tcc gaa ccc agc acc agc gct ata acc tcc gct cct ccg gcg ccg 289
Ser Ser Glu Pro Ser Thr Ser Ala Ile Thr Ser Ala Pro Pro Ala Pro
80 85 90
gcg cca ccc gcc cgc aga ccc aac cgt aga tgg gac acc aca gga acc 337
Ala Pro Pro Ala Arg Arg Pro Asn Arg Arg Trp Asp Thr Thr Gly Thr
95 100 105
ggg gtcggtaagt ccaagtgccc gccgccgcca ccgcagcagc agcagcagca 390
Gly
110
gcgccagggc taccgctcgt ggcgcgggca caagaacgcc atagtcgcct gcttgcaaga 450
ctgcgggggc aacatctctt tcgcccgccg cttcctgcta ttccaccacg gggtcgcctt 510
tccccgcaat gtcctgcatt actaccgtca tctctacagc ccctactgca gcggcgaccc 570
agaggcggca gcggcagcca cagcggcgac caccacctag gaag ata tcc tcc gcg 626
Ile Ser Ser Ala
ggc aag aca gcg gca gca gcg gcc agg aga ccc gcg gcg gca gcg gcg 674
Gly Lys Thr Ala Ala Ala Ala Ala Arg Arg Pro Ala Ala Ala Ala Ala
115 120 125 130
gga gcg gtg ggc gct ctg cgc ctc tcg ccc aac gaa ccc ctc tcg acc 722
Gly Ala Val Gly Ala Leu Arg Leu Ser Pro Asn Glu Pro Leu Ser Thr
135 140 145
cgg gag ctc aga cac agg atc ttc ccc act ttg tat gcc atc ttc caa 770
Arg Glu Leu Arg His Arg Ile Phe Pro Thr Leu Tyr Ala Ile Phe Gln
150 155 160
cag agc aga ggc cag gag cag gag ctg aaa ata aaa aac aga tct ctg 818
Gln Ser Arg Gly Gln Glu Gln Glu Leu Lys Ile Lys Asn Arg Ser Leu
165 170 175
cgc tcc ctc acc cgc agc tgt ctg tat cac aaa agc gaa gat cag ctt 866
Arg Ser Leu Thr Arg Ser Cys Leu Tyr His Lys Ser Glu Asp Gln Leu
180 185 190
cgg cgc acg ctg gag gac gcg gag gca ctc ttc agc aaa tac tgc gcg 914
Arg Arg Thr Leu Glu Asp Ala Glu Ala Leu Phe Ser Lys Tyr Cys Ala
195 200 205 210
ctc act ctt aaa gac t 930
Leu Thr Leu Lys Asp
215
<210> 31
<211> 215
<212> PRT
<213> Simian adenovirus 40
<400> 31
Met Ala Pro Arg Lys Lys Gln Gln Pro Pro Pro Gln Pro Tyr Met Leu
1 5 10 15
Leu Glu Glu Glu Glu Glu Asp Trp Asp Ser Gln Ala Glu Glu Val Ser
20 25 30
Asp Glu Glu Gln Glu Glu Met Met Glu Asp Trp Glu Glu Asp Ser Ser
35 40 45
Leu Asp Glu Glu Ala Ser Glu Ala Glu Glu Val Ala Asp Ala Thr Pro
50 55 60
Ser Pro Ser Val Ala Ala Pro Ser Pro Gly Pro Leu Lys Ser Ser Glu
65 70 75 80
Pro Ser Thr Ser Ala Ile Thr Ser Ala Pro Pro Ala Pro Ala Pro Pro
85 90 95
Ala Arg Arg Pro Asn Arg Arg Trp Asp Thr Thr Gly Thr Gly Ile Ser
100 105 110
Ser Ala Gly Lys Thr Ala Ala Ala Ala Ala Arg Arg Pro Ala Ala Ala
115 120 125
Ala Ala Gly Ala Val Gly Ala Leu Arg Leu Ser Pro Asn Glu Pro Leu
130 135 140
Ser Thr Arg Glu Leu Arg His Arg Ile Phe Pro Thr Leu Tyr Ala Ile
145 150 155 160
Phe Gln Gln Ser Arg Gly Gln Glu Gln Glu Leu Lys Ile Lys Asn Arg
165 170 175
Ser Leu Arg Ser Leu Thr Arg Ser Cys Leu Tyr His Lys Ser Glu Asp
180 185 190
Gln Leu Arg Arg Thr Leu Glu Asp Ala Glu Ala Leu Phe Ser Lys Tyr
195 200 205
Cys Ala Leu Thr Leu Lys Asp
210 215
<210> 32
<211> 37828
<212> DNA
<213> Simian adenovirus 31
<220>
<221> repeat_region
<222> (1)..(121)
<223> label=ITR
<220>
<221> CDS
<222> (2033)..(3553)
<223> label=Elb\55K
<220>
<221> CDS
<222> (3655)..(4116)
<223> label=pIX
<220>
<221> misc_feature
<222> (4181)..(5805)
<223> complement (4181..5514,5793..5805) label=IVa2
<220>
<221> misc_feature
<222> (5287)..(14232)
<223> complement (5287..8868,14224..14232) label=pol
<220>
<221> misc_feature
<222> (8670)..(14232)
<223> complement (8670..10664,14224..14232) label=pTP
<220>
<221> CDS
<222> (11118)..(12377)
<223> label=52K
<220>
<221> CDS
<222> (12404)..(14167)
<223> label=pIIIa
<220>
<221> CDS
<222> (14272)..(16038)
<223> label=penton
<220>
<221> CDS
<222> (16062)..(16655)
<223> label=pVII
<220>
<221> CDS
<222> (16721)..(17839)
<223> label=V
<220>
<221> CDS
<222> (17868)..(18110)
<223> label=pX
<220>
<221> CDS
<222> (18207)..(18965)
<223> label=pVI
<220>
<221> CDS
<222> (19077)..(21938)
<223> label=hexon
<220>
<221> CDS
<222> (21974)..(22603)
<223> label=protease
<220>
<221> misc_feature
<222> (22728)..(24395)
<223> complement label=DBP
<220>
<221> CDS
<222> (24433)..(26928)
<223> label=100K
<220>
<221> CDS
<222> (27623)..(28303)
<223> label=pVIII
<220>
<221> CDS
<222> (28307)..(28621)
<223> label=E3\12.5K
<220>
<221> CDS
<222> (29319)..(29816)
<223> label=E3\gp19K
<220>
<221> CDS
<222> (29848)..(30720)
<223> label=E3\CR1\beta
<220>
<221> CDS
<222> (31574)..(31843)
<223> label=E3\RID\alpha
<220>
<221> CDS
<222> (31849)..(32244)
<223> label=E3\RID\beta
<220>
<221> CDS
<222> (32779)..(34566)
<223> label=fiber
<220>
<221> misc_feature
<222> (34785)..(35942)
<223> complement (34785..35057,35760..35942) label=E4\orf6/7
<220>
<221> misc_feature
<222> (35061)..(35942)
<223> complement label=E4\orf6
<220>
<221> misc_feature
<222> (35845)..(36207)
<223> complement label=E4\orf4
<220>
<221> misc_feature
<222> (36224)..(36568)
<223> complement label=E4\orf3
<220>
<221> misc_feature
<222> (36568)..(36957)
<223> complement label=E4\orf2
<220>
<221> misc_feature
<222> (37019)..(37402)
<223> complement label=E4\orf1
<220>
<221> repeat_region
<222> (37708)..(37828)
<223> complement label=ITR
<400> 32
catcatcaat aatatacctt attttggatt gaagccaata tgataatgag gtgggcggag 60
cgggatgtga cgcggggcgg gaggcggggc gcggggcggg ccggcgggcg gggaggtgtg 120
gcggaagttg agtttgcaag tgtggcggat gtgacttgct agtgccggac gcggtaaaag 180
tgacgttttt cgtgtgcgcc aacgcccacg ggaagtgaca tttttcccgc ggtttttacc 240
ggatgttgta gtgaatttgg gcgtaaccaa gtaagatttg gccattttcg cgggaaaact 300
gaaacgggga agtgaaatct gattaatttc gcgttagtca taccgcgtaa tatttgtcga 360
gggccgaggg actttgaccg attacgtgga ggactcgccc aggtgttttt tgaggtgaat 420
ttccgcgttc cgggtcaaag tctccgtttt attattatag tcagctgacg cggagtgtat 480
ttataccctc tgatctcgtc aagaggccac tcttgagtgc cagcgagtag agttttctcc 540
tctgccgctc agctccgctc cgctcagctc tgacaccggg gaaaaatgag acatttcacc 600
tacgatggcg gtgtgctcac cggccagctg gctgctcagg tcctggacac cctgatcgag 660
gaggtattgg ctgataatta tcctcccgcg actcctttcg acgcacctac ccttcacgaa 720
ctgtatgatc tggaggtggt ggggcccaac gatccgaacg agcaggcggt ttccgaattt 780
tttcccgagt ccatgttgtt ggccagccag gagggggtcg aacttcagac ccctcctccg 840
atcaccgttt cccccgatcc gccgccgctg agtaggcagc ccgagcgctg cgtgggacct 900
gcgactatgc cccagctgct gcctgaggtg atcgatctca cctgtaacga gtctggtttt 960
ccacccagcg aggatgagga cgaagagggt gagcagtttg tgttagattc tgtggatcaa 1020
cccgggcgag gatgcaggtc ttgtcaatat caccggagaa acacaggaga cccccagatt 1080
atgtgttctc tgtgttatat gaagatgacc tgtatgttta tttacagtaa gtttgtgatc 1140
ggtgggcagg tgggctatag tgtgggtggg tggtctttgt ggtgtttttt tttttaatat 1200
atgttagggg gttatgctaa atactttctt attgtgattt ttttaaaagg tccagtgtct 1260
gagcccgagc aggaacctga gccggagcct gagcctcctc gccccaggag aaagcctgca 1320
attttaacta gacccagcgc accggtagcg aggggcctca gcagtgcgga gaccaccgac 1380
tccggcgctt ccgcaccatc ccctccggag attcatcctg tggtgcccct gtgtcccatt 1440
aagcccgttg ccgtgagagt tagtgggcgg cggtctgctg tggagtgcat tgaggacttg 1500
ctttttgaat cacaggaacc tttggacttg agcttgaaac gccccaggca ttagacctgg 1560
tcacctggac tgaatgagtt gacgcctatg tttgcttttg aatgacttaa tgtgtatata 1620
taataaagag tgagataatg ttttaattgc atggtgtgtt taactggggc ggagtctgct 1680
gggtgtatat aagcttccct gggctaaact tggttacact tgacctcatg gaggcctggg 1740
agtgtttgga gagctttgcc ggagtgcgtg ccttgctgga cgagagctct aacaatacct 1800
ctgggtggtg gaggtatttg tggggctctc cccagggcaa gttagtttgt aggatcaagg 1860
aggattacaa gtgggaattt gaagagcttt tgaaatcctg tggtgagcta ttggattctt 1920
tgaatctagg ccaccaggct cttttccagg agaaggtcat caggactttg gatttttcca 1980
caccggggcg cgttgcagcc ggggttgctt ttctagcttt tttgaaggat aa atg gag 2038
Met Glu
1
cga aga gac cca ctt gag ttc ggg cta cgt cct gga ttt tct ggc cat 2086
Arg Arg Asp Pro Leu Glu Phe Gly Leu Arg Pro Gly Phe Ser Gly His
5 10 15
gca act gtg gag ggc atg gat cag gca caa gaa cag gct gca act gtt 2134
Ala Thr Val Glu Gly Met Asp Gln Ala Gln Glu Gln Ala Ala Thr Val
20 25 30
gtc tac cgt ccg ccc gct gct gat tcc ggc gga gga gca aca ggc cgg 2182
Val Tyr Arg Pro Pro Ala Ala Asp Ser Gly Gly Gly Ala Thr Gly Arg
35 40 45 50
gtc aga gga ccg ggc ccg tcg gga tcc gga gca ggg ggc gcc gag gcc 2230
Val Arg Gly Pro Gly Pro Ser Gly Ser Gly Ala Gly Gly Ala Glu Ala
55 60 65
ggg cga gag gag cgc gtg gaa cct ggg aac cgg gct gag cgg cca tcc 2278
Gly Arg Glu Glu Arg Val Glu Pro Gly Asn Arg Ala Glu Arg Pro Ser
70 75 80
aca tcg gga gtg aat gtc gga cag gtg gcg gat ctt ttt cca gaa ctg 2326
Thr Ser Gly Val Asn Val Gly Gln Val Ala Asp Leu Phe Pro Glu Leu
85 90 95
cgg cgg atc ttg act atc agg gag gat ggg caa ttt gtt aag ggt ctt 2374
Arg Arg Ile Leu Thr Ile Arg Glu Asp Gly Gln Phe Val Lys Gly Leu
100 105 110
aag agg gag agg ggg gct tct gag cat aac gag gag gcc agt aat ttg 2422
Lys Arg Glu Arg Gly Ala Ser Glu His Asn Glu Glu Ala Ser Asn Leu
115 120 125 130
gct ttt agc ttg atg acc aga cac cgt cca gag tgc atc act ttt cag 2470
Ala Phe Ser Leu Met Thr Arg His Arg Pro Glu Cys Ile Thr Phe Gln
135 140 145
cag att aag gat aat tgt gcc aat gag ttg gat ctg ttg ggt cag aag 2518
Gln Ile Lys Asp Asn Cys Ala Asn Glu Leu Asp Leu Leu Gly Gln Lys
150 155 160
tat agc ata gag cag ctg acc act tac tgg ctg cag ccg ggt gat gat 2566
Tyr Ser Ile Glu Gln Leu Thr Thr Tyr Trp Leu Gln Pro Gly Asp Asp
165 170 175
ttg gag gaa gct att agg gtg tat gct aag gtg gcc ctg cgg ccc gat 2614
Leu Glu Glu Ala Ile Arg Val Tyr Ala Lys Val Ala Leu Arg Pro Asp
180 185 190
tgc aag tac aag ctg aag ggg ctg gtg aat atc agg aat tgt tgc tac 2662
Cys Lys Tyr Lys Leu Lys Gly Leu Val Asn Ile Arg Asn Cys Cys Tyr
195 200 205 210
att tct ggc aac ggg gca gag gtg gag ata gag acc gaa gac agg gtg 2710
Ile Ser Gly Asn Gly Ala Glu Val Glu Ile Glu Thr Glu Asp Arg Val
215 220 225
gcc ttc aga tgc tgc atg gtg aat atg tgg ccg ggg gtg ctg ggc atg 2758
Ala Phe Arg Cys Cys Met Val Asn Met Trp Pro Gly Val Leu Gly Met
230 235 240
gac ggg gtg gtg att atg aat gtg agg ttc acg ggt ccc aac ttt aac 2806
Asp Gly Val Val Ile Met Asn Val Arg Phe Thr Gly Pro Asn Phe Asn
245 250 255
ggc acg gtg ttc ttg ggg aac acc aac ctg gtc ctg cac ggg gtg agt 2854
Gly Thr Val Phe Leu Gly Asn Thr Asn Leu Val Leu His Gly Val Ser
260 265 270
ttc tat ggg ttt aac aac acc tgt gtg gag gcc tgg acc gat gtg aag 2902
Phe Tyr Gly Phe Asn Asn Thr Cys Val Glu Ala Trp Thr Asp Val Lys
275 280 285 290
gtc cgc ggc tgc gcc ttc tat gga tgt tgg aag gcc ata gtg agc cgc 2950
Val Arg Gly Cys Ala Phe Tyr Gly Cys Trp Lys Ala Ile Val Ser Arg
295 300 305
ccc aag agc agg agt tcc att aag aaa tgc ttg ttt gag agg tgc acc 2998
Pro Lys Ser Arg Ser Ser Ile Lys Lys Cys Leu Phe Glu Arg Cys Thr
310 315 320
ttg ggg atc ctg gcc gag ggc aac tgc agg gtg cgc cac aat gtg gcc 3046
Leu Gly Ile Leu Ala Glu Gly Asn Cys Arg Val Arg His Asn Val Ala
325 330 335
tcc gag tgc ggt tgc ttc atg ctt gtc aag agc gtg gcg ata atc aag 3094
Ser Glu Cys Gly Cys Phe Met Leu Val Lys Ser Val Ala Ile Ile Lys
340 345 350
cat aat atg gtg tgt ggc aac agc gag gac aag gcc tca cag atg ctg 3142
His Asn Met Val Cys Gly Asn Ser Glu Asp Lys Ala Ser Gln Met Leu
355 360 365 370
acc tgc gcg gat ggc aac tgc cac ttg ctg aag acc atc cat ata acc 3190
Thr Cys Ala Asp Gly Asn Cys His Leu Leu Lys Thr Ile His Ile Thr
375 380 385
agc cac ggc cgg aag gcc tgg ccc gtg ttc gag cac aac gtg ctg acc 3238
Ser His Gly Arg Lys Ala Trp Pro Val Phe Glu His Asn Val Leu Thr
390 395 400
cgc tgc tcc ttg cat ctg ggc aac agg cgc ggg gtg ttc ctg ccc tat 3286
Arg Cys Ser Leu His Leu Gly Asn Arg Arg Gly Val Phe Leu Pro Tyr
405 410 415
caa tgc aac ctt agc cac acc aag atc ttg cta gag ccc gag agc atg 3334
Gln Cys Asn Leu Ser His Thr Lys Ile Leu Leu Glu Pro Glu Ser Met
420 425 430
tcc aag gtg aac ttg aat ggg gtg ttt gac atg acc atg aag ata tgg 3382
Ser Lys Val Asn Leu Asn Gly Val Phe Asp Met Thr Met Lys Ile Trp
435 440 445 450
aag gtg ctg agg tac gac gag acc agg tcc cga tgc aga ccc tgc gag 3430
Lys Val Leu Arg Tyr Asp Glu Thr Arg Ser Arg Cys Arg Pro Cys Glu
455 460 465
tgc ggg ggc aag cat atg agg aac cag ccc gtg atg ctg gat gtg acc 3478
Cys Gly Gly Lys His Met Arg Asn Gln Pro Val Met Leu Asp Val Thr
470 475 480
gag gag ctg agg acc gac cac ttg gtt ctg gcc tgc acc agg gcc gag 3526
Glu Glu Leu Arg Thr Asp His Leu Val Leu Ala Cys Thr Arg Ala Glu
485 490 495
ttt ggt tct agc gat gaa gac acg gat tgaggtgggt gagtgggcgt 3573
Phe Gly Ser Ser Asp Glu Asp Thr Asp
500 505
ggcctggggt ggtaatgaaa atatataagt tgggggtctt agggtctctt tatttgtgtt 3633
gcagagacct ccgccggagc c atg agc ggg agc agc agc agc agc agc agc 3684
Met Ser Gly Ser Ser Ser Ser Ser Ser Ser
510 515
agc agc gcc ttg gat ggc agc atc gtg agc cct tat ttg acg acg cgg 3732
Ser Ser Ala Leu Asp Gly Ser Ile Val Ser Pro Tyr Leu Thr Thr Arg
520 525 530
atg ccc cac tgg gcc ggg gtg cgt cag aat gtg atg ggc tcc agc atc 3780
Met Pro His Trp Ala Gly Val Arg Gln Asn Val Met Gly Ser Ser Ile
535 540 545
gac ggc cga ccc gtc ttg ccc gca aat tcc gcc acg ctg acc tac gcg 3828
Asp Gly Arg Pro Val Leu Pro Ala Asn Ser Ala Thr Leu Thr Tyr Ala
550 555 560 565
acc gtc gcg ggg acg ccg ttg gac gct acc gcc gcc gcc gcc gcc acc 3876
Thr Val Ala Gly Thr Pro Leu Asp Ala Thr Ala Ala Ala Ala Ala Thr
570 575 580
gcc gcc gcc tcg gcc gtg cgc agc ctg gcc acg gac ttt gca ttc ctg 3924
Ala Ala Ala Ser Ala Val Arg Ser Leu Ala Thr Asp Phe Ala Phe Leu
585 590 595
gga cca ctg gcg aca ggg gct act tct cgg gcc gcc gct gcc gcc gtc 3972
Gly Pro Leu Ala Thr Gly Ala Thr Ser Arg Ala Ala Ala Ala Ala Val
600 605 610
cgc gat gac aag ctg acc gcc ctg ctg gcg cag ttg gat gcg ctt acc 4020
Arg Asp Asp Lys Leu Thr Ala Leu Leu Ala Gln Leu Asp Ala Leu Thr
615 620 625
cgg gaa ctg ggc gac ctt tct cag cag gtc atg gcc ctg cgc cag cag 4068
Arg Glu Leu Gly Asp Leu Ser Gln Gln Val Met Ala Leu Arg Gln Gln
630 635 640 645
gtc tcc tcc ctg caa gct ggc ggg aat gct tct ccc aca aat gcc gtt 4116
Val Ser Ser Leu Gln Ala Gly Gly Asn Ala Ser Pro Thr Asn Ala Val
650 655 660
taagataaat aaaaccagac tctgtttgga ttaaagaaaa gtagcaagtg cattgctctc 4176
tttatttcat aattctccgc gcgcgatagg cccgagacca gcgttctcgg tcgttgaggg 4236
tgcggtgtat cttctccagg acgtggtaga ggtggctctg gatgttgaga tacatgggca 4296
tgagcccgtc ccgggggtgg aggtagcacc actgcagagc ttcatgctcc ggggtggtgt 4356
tgtagatgat ccagtcgtag caggagcgct gggcatggtg cctaaaaatg tccttcagca 4416
gcaggccgat ggccaggggg aggcccttgg tgtaagtgtt tacaaaacgg ttaagttggg 4476
aagggtgcat tcggggagag atgatgtgca tcttggactg tatttttaga ttggcgatgt 4536
ttccgcccag atcccttctg ggattcatgt tgtgcaggac caccagtaca gtgtatccgg 4596
tgcacttggg gaatttgtca tgcagcttag agggaaatgc gtggaagaac ttggagacgc 4656
ccttgtggcc tcccagattt tccatgcatt cgtccatgat gatggcaatg ggcccgcggg 4716
aggcagcctg ggcaaagatg tttctggggt cactgacgtc gtagttgtgt tccagggtga 4776
ggtcgtcata ggccattttt acaaagcgcg ggcggagggt gcccgactgg gggatgatgg 4836
tcccctctgg ccccggggcg tagttgccct cgcagatctg catttcccaa gccttaatct 4896
cggagggggg aatcatatcc acctgcgggg cgatgaagaa aacggtttcc ggagccgggg 4956
agattaactg ggatgagagc aggtttctaa gcagctgtga ttttccacag ccggtgggcc 5016
cataaataac acctataacc ggctgcagct ggtagttgag agagctgcag ctgccgtcgt 5076
cccggaggag gggggccacc tcgttgagca tgtccctgac gcgcatgttc tccccgacca 5136
gatccgccag aaggcgctcg ccgcccaggg acagcagctc ttgcaaggaa gcaaagtttt 5196
tcagcggctt gaggccgtcc gccgtgggca tgtttttcag ggtctgactg agcagctcca 5256
ggcggtccca gagctcggtg acgtgctcta cggcatctct atccagcata tctcctcgtt 5316
tcgcgggttg gggcgacttt cgctgtaggg caccaagcga tgttcgtcca gcgcggccag 5376
ggtcatgtcc ttccatgggc gcagggtcct cgtcagggtg gtctgggtca cggtgaaggg 5436
gtgcgccccg ggctgggcgc tggccagggt gcgcttgagg ctggtcctgc tggtgctgaa 5496
gcgctgccgg tcttcgccct gcgcgtcggc caggtagcat ttgaccatgg tgtcgtagtc 5556
cagcccctcc gcggcgtgtc ccttggcgcg cagcttgccc ttggaggtgg cgccgcacga 5616
ggggcagagc aggctcttga gcgcgtagag cttgggggcg aggaagaccg attcggggga 5676
gtaggcgtcc gcgccgcagg ccccgcacac ggtctcgcac tccaccagcc aggtgagctc 5736
ggggcgcgcc gggtcaaaaa ccaggtttcc cccatgcttt ttgatgcgtt tcttacctcg 5796
ggtctccatg aggcggtgtc cccgctcggt gacgaagagg ctgtccgtgt ctccgtagac 5856
cgacttgagg ggtctgttct ccaggggggt ccctcggtcc tcctcgtaga ggaactcgga 5916
ccactctgag acgaaggccc gcgtccaggc caggacgaag gaggctaggt gggaggggta 5976
gcggtcgttg tccactaggg ggtccacctt ctccaaggtg tgaagacaca tgtcgccttc 6036
ctcggcgtcc aggaagatga ttggcttgta ggtgtaggcc acgtgaccgg gggtccccga 6096
cgggggggta taaaaggggg tgggggcgcg ctcgtcgtca ctctcttccg catcgctgtc 6156
tgcgagggcc agctgctggg gtgagtactc cctctcgaag gcgggcatga cctccgcgct 6216
gaggttgtca gtttccaaaa acgaggagga tttgatgttc acctgtcccg aggtgatacc 6276
tttgagggtg cccgcgtcca tctggtcaga aaacacaatc tttttattgt ccagcttggt 6336
ggcgaacgac ccatagaggg cgttggagag cagcttggcg atggagcgca gggtctggtt 6396
cttgtccctg tcggcgcgct ccttggccgc gatgttgagc tgcacgtact cgcgcgcgac 6456
gcagcgccac tcggggaaga cggtggtgcg ctcgtcgggc accaggcgca cgcgccagcc 6516
gcggttgtgc agggtgacca ggtccacgct ggtggcgacc tcgccgcgca ggcgctcgtt 6576
ggtccagcag aggcggccgc ccttgcgcga gcagaagggg ggcagggggt cgagctgggt 6636
ctcgtccggg gggtccgcgt ccacggtgaa gaccccgggg cgcaggcgcg cgtcgaagta 6696
gtcgatcttg caaccttgca tgtccagcgc ccgctgccag tcgcgggcgg cgagcgcgcg 6756
ctcgtagggg ttgagcggcg ggccccaggg catggggtgg gtgagcgcgg aggcgtacat 6816
gccgcagatg tcgtagacgt agaggggctc ccgcaggacc ccgaggtagg tggggtagca 6876
gcggccgccg cggatgctgg cgcgcacgta gtcatagagc tcgtgcgagg gggcgaggag 6936
gtcggggccc aggttggtgc gggcggggcg ctccgcgcgg aagacgatct gcctgaagat 6996
ggcatgcgag ttggaagaga tggtggggcg ctggaagacg ttgaagctgg catctcgcag 7056
gccgacggcg tcgcgcacga aggaggcgta ggagtcgcgc agcttgtgca ccagctcggc 7116
ggtgacctgc acgtcgagcg cgcagtagtc gagggtctcg cggatgatgt catacttagc 7176
ctgccccttc tttttccaca gctcgcggtt gaggacaaac tcttcgcggt ctttccagta 7236
ctcttggatc gggaaaccgt ccggttccga acggtaagag cctagcatgt agaactggtt 7296
gacggcctgg taggcgcagc agcccttctc cacggggagg gcgtaggcct gcgcggcctt 7356
gcggagcgag gtgtgggtca gggcgaaggt gtccctgacc atgactttga ggtactggtg 7416
cttgaagtcg gagtcgtcgc agccgccctg ctcccagagc gagaagtcgg tgcgcttctt 7476
ggagcggggg ttgggcagcg cgaaggtgac atcgttgaag aggatcttgc ccgcgcgggg 7536
catgaagttg cgggtgatgc ggaagggccc cggcacctcg gagcggttgt tgatgacctg 7596
ggcggcgagc acgatctcgt cgaagccgtt gatgttgtgg ccgacgatgt agagttccag 7656
gaagcggggc cggcccttga cggtgggcag cttctttagc tcttcgtagg tgagctcctc 7716
gggcgaggcg aggccgtgct cggccagggc ccagtccgcc aggtgcgggt tgtctctgag 7776
gaaggagtcc cagaggtcgc gggccaggag ggtctgcagg cggtccctga aagtcctgaa 7836
ctggcgaccc acggccatct tttcgggggt gatgcagtag aaggtgaggg ggtcttgctg 7896
ccagcggtcc cagtcgagct gcagggcgag gtcgcgcgcg gcggcgacca ggcgctcgtc 7956
gcccccgaat ttcatgacca gcatgaaggg cacgagctgc tttccgaagg cccccatcca 8016
agtgtaggtc tctacatcgt aggtgacaaa gaggcgctcc gtgcgaggat gcgagccgat 8076
cgggaagaac tggatctccc gccaccagtt ggaggagtgg ctgttgatgt ggtggaagta 8136
gaagtcccgt cgccgggccg aacactcgtg ctggcttttg taaaagcgag cgcagtactg 8196
gcagcgctgc acgggctgta cctcctgcac gagatgcacc ttccggccgc gcacgaggaa 8256
ggcgaggggg aatctgagcc ccccgcctgg ctcgcggcat ggctggtgct cttctacttt 8316
ggatgcgtgt ccgtctccgt ctggctcctc gaggggtgtt acggtggagc ggaccaccac 8376
gccgcgcgag ccgcaggtcc agatatcggc gcgcggcggt cggagtttga tgacgacatc 8436
gcgcagctgg gagctgtcca tggtctggag ctcccgcggc ggcggcaggt cagccgggag 8496
ttcttgcagg ttcacctcgc agagtcgggc cagggcgcgg ggcaggtcca ggtggtacct 8556
gatctctagg ggcgtgttgg tggcggcgtc gatggcttgc aggagcccgc agccccgggg 8616
cgcgacgacg gtgccccgcg gggtggtggt ggtggtagtg gtgatgctgc ttagaagcgg 8676
tgccgcgggc gggcccccgg aggtaggggg ggctccggtc ccgcgggcag gggcggcagc 8736
ggcacgtcgg cgtggagcgc gggcaggagt tggtgctgcg cccggaggtt gctggcgaag 8796
gcgacgacgc ggcggttgat ctcctggatc tggcgcctct gcgtgaagac gacgggcccg 8856
gtgagcttga acctgaaaga gagttcaaca gaatcaatct cggtgtcatt gaccgcggcc 8916
tggcgcagga tctcctgcac gtctcccgag ttgtcttggt aggcgatctc ggccatgaac 8976
tgctcgatct cttcctcctg gaggtctccg cgtccggcgc gctccacggt ggccgccagg 9036
tcgttggaga tgcgccccat gagctgcgag aaggcgttga gtccgccctc gttccagact 9096
cggctgtaga ccacgccccc ctggtcgtcg cgggcgcgca tgaccacctg cgcgaggttg 9156
agttccacgt gccgcgcgaa gacggcgtag ttgcgcagac gctggaagag gtagttgagg 9216
gtggtggcgg tgtgctcggc cacgaagaag ttcatgaccc agcggcgcaa cgtggattcg 9276
ttgatgtccc ccaaggcctc cagccgttcc atggcctcgt agaagtccac ggcgaagttg 9336
aaaaactggg agttgcgcgc cgacacggtc aactcctcct ccagaagacg gatgagctcg 9396
gcgacggtgt cgcgcacctc gcgctcgaag gctatgggga tctcttcctc cgctagcatc 9456
accacctcct cctcctcttc tggcacttcc atgatggctt cttcctcttc ggggggcggc 9516
ggcggcggtg ggggaggggg cgctcggcgc cggcggcggc gcaccgggag gcggtccacg 9576
aagcgcgcga tcatctcccc gcggcggcgg cgcatggtct cggtgacggc gcggccgttc 9636
tcccgggggc gcagctggaa gacgccgccg gacatctggt gctggggcgg gtggccgtga 9696
ggcagggaga cggcgctgac gatgcatctc aacaattgct gcgtaggtac gccgccgagg 9756
gacctgaggg agtccatatc caccggatcc gaaaaccttt cgaggaaagc gtctaaccag 9816
tcgcagtcgc aaggtaggct gagcaccgtg gcgggcggcg gggggtgggg ggagtgtctg 9876
gcggaggtgc tgctgatgat gtaattgaag taggcggact tgacacggcg gatggtcgac 9936
aggagcacca tgtccttggg cccggcctgc tggatgcgga ggcggtcggc tatgccccag 9996
gcttcgttct ggcatcggcg caggtccttg tagtagtctt gcatgagcct ttccaccggc 10056
acctcttctc cttcctcttc tgcttcttcc atctgtgctt cggcccgggg gcggcgtcgc 10116
tgcgcccccc tgccacccat gcgcgtgacc ccgaaccccc tgagcggctg gagcagggcc 10176
aggtcggcga cgacgcgctc ggccaggatg gcctgctgca cctgcgtgag ggtggtctgg 10236
aagtcatcca agtccacgaa gcggtggtag gcgcccgtgt tgatggtgta ggtgcagttg 10296
gccatgacgg accagttgac ggtctggtgg cccggttgcg acatctcggt gtacctgagt 10356
cgcgagtagg cgcgggagtc gaagacgtag tcgttgcaag tccgcaccag gtactggtag 10416
cccaccagga agtgcggcgg cggctggcgg tagaggggcc agcgcagggt ggcgggggct 10476
ccgggggcca ggtcttccag catgaggcgg tggtaggcgt agatgtacct ggacatccag 10536
gtgatacctg cggcggtggt ggaggcgcgc gggaagtcgc gcacccggtt ccagatgttg 10596
cgcaggggca gaaagtgctc catggtaggc gtgctctgtc cagtcagacg cgcgcagtcg 10656
ttgatactct agaccaggga aaacgaaagc cggtcagcgg gcactcttcc gtggtctggt 10716
gaatagatcg caagggtatc atggcggagg gcctcggttc gagccccggg tccgggccgg 10776
acggtccgcc atgatccacg cggttaccgc ccgcgtgtcg aacccaggtg tgcgacgtca 10836
gacaacggtg gagtgttcct tttggcgttt ttctggccgg gcgccggcgc cgcgtaagag 10896
actaaggcgc gaaagcgaaa gcagtaagtg gctcgctccc cgtagccgga gggatccttg 10956
ctaagggttg cgttgcggcg aaccccggtt cgaatcctat actcgggccg gccggacccg 11016
cggctaaggt gtcggattgg cctccccctc gtataaagac cccgcttgcg gattgactcc 11076
ggacacgggg acgagccccc ttttattttt gctttcccca g atg cat ccg gtg ctg 11132
Met His Pro Val Leu
665
cgg cag atg cgc ccc ccg ccc cag cag caa cac cag cag caa gag cgg 11180
Arg Gln Met Arg Pro Pro Pro Gln Gln Gln His Gln Gln Gln Glu Arg
670 675 680
cag cca cag cag cag cag cgg gag tca tgc agg gcc ccc tcg ccc acc 11228
Gln Pro Gln Gln Gln Gln Arg Glu Ser Cys Arg Ala Pro Ser Pro Thr
685 690 695
ctt ggc ggc ccg gcc act tcg gcg tcc gcg gcc gtg tcc ggc gcc ggc 11276
Leu Gly Gly Pro Ala Thr Ser Ala Ser Ala Ala Val Ser Gly Ala Gly
700 705 710
ggc ggc ggc ggg ggg ctg gcg gac gac ccc gag gag ccc ccg cgg cgc 11324
Gly Gly Gly Gly Gly Leu Ala Asp Asp Pro Glu Glu Pro Pro Arg Arg
715 720 725 730
agg gcc aga cac tac ctg gac ctg gag gag ggc gag ggc ctg gcg cgg 11372
Arg Ala Arg His Tyr Leu Asp Leu Glu Glu Gly Glu Gly Leu Ala Arg
735 740 745
ctg ggg gcg ccg tct ccc gag cgc cac ccg cgg gtg cag ctg aag cgc 11420
Leu Gly Ala Pro Ser Pro Glu Arg His Pro Arg Val Gln Leu Lys Arg
750 755 760
gac tcg cgc gag gcg tac gtg cct cgg cag aac ctg ttc agg gac cgc 11468
Asp Ser Arg Glu Ala Tyr Val Pro Arg Gln Asn Leu Phe Arg Asp Arg
765 770 775
gcg ggc gag gag ccc gag gag atg cgg gac agg agg ttc agc gcg ggg 11516
Ala Gly Glu Glu Pro Glu Glu Met Arg Asp Arg Arg Phe Ser Ala Gly
780 785 790
cgg gag ctg cgg cag ggg ctg aac cgc gag cgc ttg ctg cgc gag gag 11564
Arg Glu Leu Arg Gln Gly Leu Asn Arg Glu Arg Leu Leu Arg Glu Glu
795 800 805 810
gac ttt gag ccc gac gcg cgg acg ggg atc agc ccc gcg cgc gcg cac 11612
Asp Phe Glu Pro Asp Ala Arg Thr Gly Ile Ser Pro Ala Arg Ala His
815 820 825
gtg gcg gcc gcc gac ctg gtg acg gcg tac gag cag acg gtg aac cag 11660
Val Ala Ala Ala Asp Leu Val Thr Ala Tyr Glu Gln Thr Val Asn Gln
830 835 840
gag att aac ttc caa aag agt ttc aac aac cac gtg cgc acg ctg gtg 11708
Glu Ile Asn Phe Gln Lys Ser Phe Asn Asn His Val Arg Thr Leu Val
845 850 855
gcg cgc gag gag gtg acc atc ggg ctg atg cac ctg tgg gac ttt gtg 11756
Ala Arg Glu Glu Val Thr Ile Gly Leu Met His Leu Trp Asp Phe Val
860 865 870
agc gcg ctg gtg cag aac ccc aac agc aag cct ctg acg gcg cag ctg 11804
Ser Ala Leu Val Gln Asn Pro Asn Ser Lys Pro Leu Thr Ala Gln Leu
875 880 885 890
ttc ctg ata gtg cag cac agc agg gac aac gag gcg ttc agg gac gcg 11852
Phe Leu Ile Val Gln His Ser Arg Asp Asn Glu Ala Phe Arg Asp Ala
895 900 905
ctg ctg aac atc acc gag ccc gag ggc cgg tgg ctg ctg gac ctg att 11900
Leu Leu Asn Ile Thr Glu Pro Glu Gly Arg Trp Leu Leu Asp Leu Ile
910 915 920
aac atc ctg cag agc ata gtg gtg cag gag cgc agc ctg agc ctg gcc 11948
Asn Ile Leu Gln Ser Ile Val Val Gln Glu Arg Ser Leu Ser Leu Ala
925 930 935
gac aag gtg gcg gcc atc aac tac tcg atg ctg agt ctg ggc aag ttt 11996
Asp Lys Val Ala Ala Ile Asn Tyr Ser Met Leu Ser Leu Gly Lys Phe
940 945 950
tac gcg cgc aag atc tac cag acg ccg tac gtg ccc ata gac aag gag 12044
Tyr Ala Arg Lys Ile Tyr Gln Thr Pro Tyr Val Pro Ile Asp Lys Glu
955 960 965 970
gtg aag atc gac ggc ttt tac atg cgc atg gcg ctg aag gtg ctg acc 12092
Val Lys Ile Asp Gly Phe Tyr Met Arg Met Ala Leu Lys Val Leu Thr
975 980 985
ctg agc gac gac ctg ggc gtg tac cgc aac gag cgc atc cac aag gcc 12140
Leu Ser Asp Asp Leu Gly Val Tyr Arg Asn Glu Arg Ile His Lys Ala
990 995 1000
gtg agc gtg agc cgg cgg cgc gag ctg agc gac cgc gag ctg atg 12185
Val Ser Val Ser Arg Arg Arg Glu Leu Ser Asp Arg Glu Leu Met
1005 1010 1015
cac agc ctg cag cgg gcg ctg gcg ggc gcc ggc agc ggc gac agg 12230
His Ser Leu Gln Arg Ala Leu Ala Gly Ala Gly Ser Gly Asp Arg
1020 1025 1030
gag gcg gag tcc tac ttc gat gcg ggg gcg gac ctg cgc tgg gcg 12275
Glu Ala Glu Ser Tyr Phe Asp Ala Gly Ala Asp Leu Arg Trp Ala
1035 1040 1045
ccc agc cgg cgg gcc ctg gag gcc gcg ggg gtc cgc gag gac tat 12320
Pro Ser Arg Arg Ala Leu Glu Ala Ala Gly Val Arg Glu Asp Tyr
1050 1055 1060
gac gag gac ggc gag gag gat gag gag tac gag cta gag gag ggc 12365
Asp Glu Asp Gly Glu Glu Asp Glu Glu Tyr Glu Leu Glu Glu Gly
1065 1070 1075
gag tac ctg gac taaaccgcgg gtggtgtttc cggtag atg caa gac ccg 12415
Glu Tyr Leu Asp Met Gln Asp Pro
1080 1085
aac gtg gtg gac ccg gcg ctg cgg gcg gct ctg cag agc cag ccg 12460
Asn Val Val Asp Pro Ala Leu Arg Ala Ala Leu Gln Ser Gln Pro
1090 1095 1100
tcc ggc ctt aac tcc tca gac gac tgg cga cag gtc atg gac cgc 12505
Ser Gly Leu Asn Ser Ser Asp Asp Trp Arg Gln Val Met Asp Arg
1105 1110 1115
atc atg tcg ctg acg gcg cgc aac ccg gac gcg ttc cgg cag cag 12550
Ile Met Ser Leu Thr Ala Arg Asn Pro Asp Ala Phe Arg Gln Gln
1120 1125 1130
ccg cag gcc aac agg ctc tcc gcc atc ctg gag gcg gtg gtg cct 12595
Pro Gln Ala Asn Arg Leu Ser Ala Ile Leu Glu Ala Val Val Pro
1135 1140 1145
gcg cgc tcg aac ccc acg cac gag aag gtg ctg gcc ata gtg aac 12640
Ala Arg Ser Asn Pro Thr His Glu Lys Val Leu Ala Ile Val Asn
1150 1155 1160
gcg ctg gcc gag aac agg gcc atc cgc ccg gac gag gcc ggg ctg 12685
Ala Leu Ala Glu Asn Arg Ala Ile Arg Pro Asp Glu Ala Gly Leu
1165 1170 1175
gtg tac gac gcg ctg ctg cag cgc gtg gcc cgc tac aac agc ggc 12730
Val Tyr Asp Ala Leu Leu Gln Arg Val Ala Arg Tyr Asn Ser Gly
1180 1185 1190
aac gtg cag acc aac ctg gac cgg ctg gtg ggg gac gtg cgc gag 12775
Asn Val Gln Thr Asn Leu Asp Arg Leu Val Gly Asp Val Arg Glu
1195 1200 1205
gcg gtg gcg cag cgc gag cgc gcg gat cgg cag ggc aac ctg ggc 12820
Ala Val Ala Gln Arg Glu Arg Ala Asp Arg Gln Gly Asn Leu Gly
1210 1215 1220
tcc atg gtg gcg ctg aac gcc ttc ctg agc acg cag ccg gcc aac 12865
Ser Met Val Ala Leu Asn Ala Phe Leu Ser Thr Gln Pro Ala Asn
1225 1230 1235
gtg ccg cgg ggg cag gag gac tac acc aac ttt gtg agc gcg ctg 12910
Val Pro Arg Gly Gln Glu Asp Tyr Thr Asn Phe Val Ser Ala Leu
1240 1245 1250
cgg ctg atg gtg acc gag acc ccc cag agc gag gtg tac cag tcg 12955
Arg Leu Met Val Thr Glu Thr Pro Gln Ser Glu Val Tyr Gln Ser
1255 1260 1265
ggc ccg gac tac ttc ttc cag acc agc aga cag ggc ctg caa acg 13000
Gly Pro Asp Tyr Phe Phe Gln Thr Ser Arg Gln Gly Leu Gln Thr
1270 1275 1280
gtg aac ctg agc cag gct ttc aag aac ctg cgg ggg ctg tgg ggc 13045
Val Asn Leu Ser Gln Ala Phe Lys Asn Leu Arg Gly Leu Trp Gly
1285 1290 1295
gtg aag gcg ccc acc ggg gac cgg gcg acg gtg tcc agc ctg ctg 13090
Val Lys Ala Pro Thr Gly Asp Arg Ala Thr Val Ser Ser Leu Leu
1300 1305 1310
acg ccc aac tcg cgc ctg ctg ctg cta ctg atc gcg ccg ttc acg 13135
Thr Pro Asn Ser Arg Leu Leu Leu Leu Leu Ile Ala Pro Phe Thr
1315 1320 1325
gac agc ggc agc gtg tcc cgg gac acc tac ctg ggg cac ctg ctg 13180
Asp Ser Gly Ser Val Ser Arg Asp Thr Tyr Leu Gly His Leu Leu
1330 1335 1340
acc ctg tac cgc gag gcc atc ggg cag gcg cag gtg gac gag cac 13225
Thr Leu Tyr Arg Glu Ala Ile Gly Gln Ala Gln Val Asp Glu His
1345 1350 1355
acc ttc caa gag atc acc agc gtg agc cgc gcg ctg ggg cag gag 13270
Thr Phe Gln Glu Ile Thr Ser Val Ser Arg Ala Leu Gly Gln Glu
1360 1365 1370
gac acg agc agc ctg gag gcg act ctg aac tac ctg ctg acc aac 13315
Asp Thr Ser Ser Leu Glu Ala Thr Leu Asn Tyr Leu Leu Thr Asn
1375 1380 1385
cgg cgg cag aag atc ccc tcg ctg cac agc ctg acc tcc gag gag 13360
Arg Arg Gln Lys Ile Pro Ser Leu His Ser Leu Thr Ser Glu Glu
1390 1395 1400
gag cgc atc ctg cgc tac gtg cag cag agc gtg agc ctg aac ctg 13405
Glu Arg Ile Leu Arg Tyr Val Gln Gln Ser Val Ser Leu Asn Leu
1405 1410 1415
atg cgc gac ggt gtg acg ccc agc gtg gcg ctg gac atg acc gcg 13450
Met Arg Asp Gly Val Thr Pro Ser Val Ala Leu Asp Met Thr Ala
1420 1425 1430
cgc aac atg gaa ccg ggc atg tac gcc gcg cac cgg cct tac atc 13495
Arg Asn Met Glu Pro Gly Met Tyr Ala Ala His Arg Pro Tyr Ile
1435 1440 1445
aac cgc ctg atg gac tac ctg cat cgc gcg gcg gcc gtg aac ccc 13540
Asn Arg Leu Met Asp Tyr Leu His Arg Ala Ala Ala Val Asn Pro
1450 1455 1460
gag tac ttc acc aac gcc atc ctg aac ccg cac tgg ctc ccg ccg 13585
Glu Tyr Phe Thr Asn Ala Ile Leu Asn Pro His Trp Leu Pro Pro
1465 1470 1475
ccc ggg ttc tac agc ggg ggc ttc gag gtt ccc gag gcc aac gat 13630
Pro Gly Phe Tyr Ser Gly Gly Phe Glu Val Pro Glu Ala Asn Asp
1480 1485 1490
ggc ttc ctg tgg gac gac atg gac gac agc gtg ttc tcc ccg cgg 13675
Gly Phe Leu Trp Asp Asp Met Asp Asp Ser Val Phe Ser Pro Arg
1495 1500 1505
ccg cag gcg ctg gcg gag gcg tcc ctg ctg cgt ccc aag aag gag 13720
Pro Gln Ala Leu Ala Glu Ala Ser Leu Leu Arg Pro Lys Lys Glu
1510 1515 1520
gag agt cgc cac ggt ccc cgc ggc agt agc gct tct ctg tcc gag 13765
Glu Ser Arg His Gly Pro Arg Gly Ser Ser Ala Ser Leu Ser Glu
1525 1530 1535
ctg ggg gcg gcc gcc gcg cgc ccc ggg tcc cta ggg ggc agc ccc 13810
Leu Gly Ala Ala Ala Ala Arg Pro Gly Ser Leu Gly Gly Ser Pro
1540 1545 1550
ttt ccg agc ctg gtg ggg tct ctg caa agc ggg cgc acc acc cgc 13855
Phe Pro Ser Leu Val Gly Ser Leu Gln Ser Gly Arg Thr Thr Arg
1555 1560 1565
ccg cga ctg ctg ggc gag gac gag tac ctg aac aac tcc ctg atg 13900
Pro Arg Leu Leu Gly Glu Asp Glu Tyr Leu Asn Asn Ser Leu Met
1570 1575 1580
cag ccg gtg cgg gag aaa aac ctg ccc ccc gca ttt ccc aac aac 13945
Gln Pro Val Arg Glu Lys Asn Leu Pro Pro Ala Phe Pro Asn Asn
1585 1590 1595
ggg ata gag agc ctg gtg gac aag atg agc aga tgg aag acc tat 13990
Gly Ile Glu Ser Leu Val Asp Lys Met Ser Arg Trp Lys Thr Tyr
1600 1605 1610
gcg cag gag cac agg gac gcg ccc gcg ctc cgc ccg ccc acg cgg 14035
Ala Gln Glu His Arg Asp Ala Pro Ala Leu Arg Pro Pro Thr Arg
1615 1620 1625
cgc cag cgc cac gac cgg cag cgg ggg ctg gtg tgg gat gac gag 14080
Arg Gln Arg His Asp Arg Gln Arg Gly Leu Val Trp Asp Asp Glu
1630 1635 1640
gac tcc gcg gac gat agc agc gtg ctg gac ctg gga ggg agc ggc 14125
Asp Ser Ala Asp Asp Ser Ser Val Leu Asp Leu Gly Gly Ser Gly
1645 1650 1655
aac ccg ttc gcg cac ctg cgc ccc cgc ctg ggg agg atg ttt 14167
Asn Pro Phe Ala His Leu Arg Pro Arg Leu Gly Arg Met Phe
1660 1665
taaaaaagca agaagcatga tgcaaaaaat tggataatta atataataaa actcaccaag 14227
gccatggcga ccgagcgttg gtttcttgtt gtgttccctt tagt atg cga cgc gcg 14283
Met Arg Arg Ala
1670
gcg atg tac cag gag gga cct cct ccc tct tac gag agc gtg gtg 14328
Ala Met Tyr Gln Glu Gly Pro Pro Pro Ser Tyr Glu Ser Val Val
1675 1680 1685
ggc gcg gct tct ccc ttt gcg tca cag ctg gag ccg ccg tac gtg 14373
Gly Ala Ala Ser Pro Phe Ala Ser Gln Leu Glu Pro Pro Tyr Val
1690 1695 1700
cct ccg cgc tac ctg cgg cct acg ggg ggg aga aac agc atc cgt 14418
Pro Pro Arg Tyr Leu Arg Pro Thr Gly Gly Arg Asn Ser Ile Arg
1705 1710 1715
tac tcg gag ctg gcg ccc ctg ttc gac acc acc cgg gtg tac ctg 14463
Tyr Ser Glu Leu Ala Pro Leu Phe Asp Thr Thr Arg Val Tyr Leu
1720 1725 1730
gtg gac aac aag tcg gcg gac gtg gcc tcc ctg aac tac cag aac 14508
Val Asp Asn Lys Ser Ala Asp Val Ala Ser Leu Asn Tyr Gln Asn
1735 1740 1745
gac cac agc aat ttt ttg acc acg gtc atc cag aac aat gac tac 14553
Asp His Ser Asn Phe Leu Thr Thr Val Ile Gln Asn Asn Asp Tyr
1750 1755 1760
agc ccg agc gag gcc agc acc cag acc atc aat ctg gat gac cgg 14598
Ser Pro Ser Glu Ala Ser Thr Gln Thr Ile Asn Leu Asp Asp Arg
1765 1770 1775
tcg cac tgg ggc ggc gac ctg aaa acc atc ctg cac acc aac atg 14643
Ser His Trp Gly Gly Asp Leu Lys Thr Ile Leu His Thr Asn Met
1780 1785 1790
ccc aac gtg aac gag ttc atg ttc acc aat aag ttc aag gcg cgg 14688
Pro Asn Val Asn Glu Phe Met Phe Thr Asn Lys Phe Lys Ala Arg
1795 1800 1805
gtg atg gtg tcg cgc tcg cac acc aag gac gac cgg gtg gag ctg 14733
Val Met Val Ser Arg Ser His Thr Lys Asp Asp Arg Val Glu Leu
1810 1815 1820
aag tac gag tgg gtg gag ttc gag ctg ccc gag ggc aac tac tcc 14778
Lys Tyr Glu Trp Val Glu Phe Glu Leu Pro Glu Gly Asn Tyr Ser
1825 1830 1835
gag acc atg acc att gac ctg atg aac aac gcg atc gtg gag cac 14823
Glu Thr Met Thr Ile Asp Leu Met Asn Asn Ala Ile Val Glu His
1840 1845 1850
tat ctg aaa gtg ggc agg cag aac ggg gtt ctg gag agc gac atc 14868
Tyr Leu Lys Val Gly Arg Gln Asn Gly Val Leu Glu Ser Asp Ile
1855 1860 1865
ggg gtg aag ttc gac acc agg aac ttc cgc ctg ggg ctg gac ccc 14913
Gly Val Lys Phe Asp Thr Arg Asn Phe Arg Leu Gly Leu Asp Pro
1870 1875 1880
gtg acc ggg ctg gtc atg ccc ggg gtg tac acc aac gag gcc ttc 14958
Val Thr Gly Leu Val Met Pro Gly Val Tyr Thr Asn Glu Ala Phe
1885 1890 1895
cat ccc gac atc gtc ctg ctg ccc ggc tgc ggg gtg gac ttc acc 15003
His Pro Asp Ile Val Leu Leu Pro Gly Cys Gly Val Asp Phe Thr
1900 1905 1910
tac agc cgc ctg agc aac ctc ctg ggc atc cgc aag cgg cag ccc 15048
Tyr Ser Arg Leu Ser Asn Leu Leu Gly Ile Arg Lys Arg Gln Pro
1915 1920 1925
ttc cag gag ggc ttc agg atc acc tac gag gac ctg gag ggg ggc 15093
Phe Gln Glu Gly Phe Arg Ile Thr Tyr Glu Asp Leu Glu Gly Gly
1930 1935 1940
aac atc ccc gcg ctc ctc gat gtg gag gcc tac cag gat agc tta 15138
Asn Ile Pro Ala Leu Leu Asp Val Glu Ala Tyr Gln Asp Ser Leu
1945 1950 1955
aag gaa aac gag gcg ggg cag gag gac acc gcc tcc gcc gcc gcc 15183
Lys Glu Asn Glu Ala Gly Gln Glu Asp Thr Ala Ser Ala Ala Ala
1960 1965 1970
gct gca gcc gcc gcc acc ccc gct gag cag ggc gag gat gcc gcc 15228
Ala Ala Ala Ala Ala Thr Pro Ala Glu Gln Gly Glu Asp Ala Ala
1975 1980 1985
gcc gca gcc ggc gcg gcc gag gcg gag gcc gaa ccc gcc atg gtg 15273
Ala Ala Ala Gly Ala Ala Glu Ala Glu Ala Glu Pro Ala Met Val
1990 1995 2000
gtg gag gag cag gag gag gac atg aat gac agc gcg gtg cgc gga 15318
Val Glu Glu Gln Glu Glu Asp Met Asn Asp Ser Ala Val Arg Gly
2005 2010 2015
gac acc ttc gtc acc cgg ggg gag gaa aag caa gcg gag gcc gag 15363
Asp Thr Phe Val Thr Arg Gly Glu Glu Lys Gln Ala Glu Ala Glu
2020 2025 2030
gcc gcg gcc gag gag aag cag gcg gcg gag gcg gca gcg gct ttg 15408
Ala Ala Ala Glu Glu Lys Gln Ala Ala Glu Ala Ala Ala Ala Leu
2035 2040 2045
gcc gcg gca gag gcg gct gag gct gag tcg gag ggg gcc aag aag 15453
Ala Ala Ala Glu Ala Ala Glu Ala Glu Ser Glu Gly Ala Lys Lys
2050 2055 2060
gag ccc gtg att aag ccc ctg acc gaa gat agc aag aag cgc agt 15498
Glu Pro Val Ile Lys Pro Leu Thr Glu Asp Ser Lys Lys Arg Ser
2065 2070 2075
tac aac gtg ctc aag gac agc acc aac acc gcg tac cgc agc tgg 15543
Tyr Asn Val Leu Lys Asp Ser Thr Asn Thr Ala Tyr Arg Ser Trp
2080 2085 2090
tac ctg gcc tac aac tac ggc gac ccg tcg acg ggg gtg cgc tcc 15588
Tyr Leu Ala Tyr Asn Tyr Gly Asp Pro Ser Thr Gly Val Arg Ser
2095 2100 2105
tgg acc ctg ctg tgc acg ccg gac gtg acc tgc ggc tcg gag cag 15633
Trp Thr Leu Leu Cys Thr Pro Asp Val Thr Cys Gly Ser Glu Gln
2110 2115 2120
gtg tac tgg tcg ctg ccc gac atg atg caa gac ccc gtg acc ttc 15678
Val Tyr Trp Ser Leu Pro Asp Met Met Gln Asp Pro Val Thr Phe
2125 2130 2135
cgc tcc acg cgg cag gtc agc aac ttc ccg gtg gtg ggc gcc gag 15723
Arg Ser Thr Arg Gln Val Ser Asn Phe Pro Val Val Gly Ala Glu
2140 2145 2150
ctg ctg ccc gtg cac tcc aag agc ttc tac aac gac cag gcc gtc 15768
Leu Leu Pro Val His Ser Lys Ser Phe Tyr Asn Asp Gln Ala Val
2155 2160 2165
tac tcc cag ctc atc cgc cag ttc acc tct ctg acc cac gtg ttc 15813
Tyr Ser Gln Leu Ile Arg Gln Phe Thr Ser Leu Thr His Val Phe
2170 2175 2180
aat cgc ttt cct gag aac cag att ctg gcg cgc ccg ccc gcc ccc 15858
Asn Arg Phe Pro Glu Asn Gln Ile Leu Ala Arg Pro Pro Ala Pro
2185 2190 2195
acc atc acc acc gtc agt gaa aac gtt cct gct ctc aca gat cac 15903
Thr Ile Thr Thr Val Ser Glu Asn Val Pro Ala Leu Thr Asp His
2200 2205 2210
ggg acg cta ccg ctg cgc aac agc atc gga gga gtc cag cga gtg 15948
Gly Thr Leu Pro Leu Arg Asn Ser Ile Gly Gly Val Gln Arg Val
2215 2220 2225
acc gtt act gac gcc aga cgc cgc acc tgc ccc tac gtt tac aag 15993
Thr Val Thr Asp Ala Arg Arg Arg Thr Cys Pro Tyr Val Tyr Lys
2230 2235 2240
gcc ttg ggc ata gtc tct ccg cgc gtc ctt tcc agc cgc act ttt 16038
Ala Leu Gly Ile Val Ser Pro Arg Val Leu Ser Ser Arg Thr Phe
2245 2250 2255
tgagcaaaac acccaccatc atc atg tcc atc ctg atc tcg ccc agc aat 16088
Met Ser Ile Leu Ile Ser Pro Ser Asn
2260 2265
aac tcc ggc tgg gga ctg ctg cgc gcg ccc agc aag atg ttc gga 16133
Asn Ser Gly Trp Gly Leu Leu Arg Ala Pro Ser Lys Met Phe Gly
2270 2275 2280
ggg gcg agg aag cgc tcc gag cag cac ccc gtg cgc gtg cgc ggg 16178
Gly Ala Arg Lys Arg Ser Glu Gln His Pro Val Arg Val Arg Gly
2285 2290 2295
cac ttc cgc gcc ccc tgg gga gcg cac aaa cgc ggc cgc acg ggg 16223
His Phe Arg Ala Pro Trp Gly Ala His Lys Arg Gly Arg Thr Gly
2300 2305 2310
cgc acc acc gtg gac gac gcc atc gac tcg gtg gtg gag cag gcg 16268
Arg Thr Thr Val Asp Asp Ala Ile Asp Ser Val Val Glu Gln Ala
2315 2320 2325
cgc aac tac agg ccc gcg gtc tcc acc gtg gac gcg gcc atc cag 16313
Arg Asn Tyr Arg Pro Ala Val Ser Thr Val Asp Ala Ala Ile Gln
2330 2335 2340
aca gtg gtg cag ggc gcg cgg cgg tac gcc aag ctg aag agc cgc 16358
Thr Val Val Gln Gly Ala Arg Arg Tyr Ala Lys Leu Lys Ser Arg
2345 2350 2355
cgg aag cgc gtg gcc cgc cgc cac cgc cgc cga ccc ggg gcc gcc 16403
Arg Lys Arg Val Ala Arg Arg His Arg Arg Arg Pro Gly Ala Ala
2360 2365 2370
gcc aaa cgc gcc gcc gcc gcc ctg ctt cgc cgg gcc aag cgc acg 16448
Ala Lys Arg Ala Ala Ala Ala Leu Leu Arg Arg Ala Lys Arg Thr
2375 2380 2385
ggc cgc cgc gcc gcc atg agg gcc gcg cgc cgc ctg gcc gcc ggc 16493
Gly Arg Arg Ala Ala Met Arg Ala Ala Arg Arg Leu Ala Ala Gly
2390 2395 2400
atc acc gcc acc gcc atg gcc ccc cgc acc cga aga cgc gcg gcc 16538
Ile Thr Ala Thr Ala Met Ala Pro Arg Thr Arg Arg Arg Ala Ala
2405 2410 2415
gcc gcc gcc gcc gcg gcc atc agc gac atg gcc acc agg cgc cgg 16583
Ala Ala Ala Ala Ala Ala Ile Ser Asp Met Ala Thr Arg Arg Arg
2420 2425 2430
ggc aac gtg tac tgg gtg cgc gac tcg gtg agc ggt gtg cgc gtg 16628
Gly Asn Val Tyr Trp Val Arg Asp Ser Val Ser Gly Val Arg Val
2435 2440 2445
ccc gtg cgc ttc cgc ccc ccg cgg act tgatgtgtga aaaacaacac 16675
Pro Val Arg Phe Arg Pro Pro Arg Thr
2450 2455
tgagtctcct gctgttgtgt gtatcccagc ggcgcgcgca gcgac atg tcc aag 16729
Met Ser Lys
cgc aaa atc aaa gaa gag atg ctc cag gtc atc gcg ccg gag atc 16774
Arg Lys Ile Lys Glu Glu Met Leu Gln Val Ile Ala Pro Glu Ile
2460 2465 2470
tat ggg ccc ccg aag aag gaa gag cag gat ttc aag tcc cgc aag 16819
Tyr Gly Pro Pro Lys Lys Glu Glu Gln Asp Phe Lys Ser Arg Lys
2475 2480 2485
ata aag cgg gtc aaa aag aaa aag aaa gat gat gat gcc gat ggg 16864
Ile Lys Arg Val Lys Lys Lys Lys Lys Asp Asp Asp Ala Asp Gly
2490 2495 2500
gag gtg gag ttt ctg cgc gcc acg gcg ccc agg cgc ccg gtg cag 16909
Glu Val Glu Phe Leu Arg Ala Thr Ala Pro Arg Arg Pro Val Gln
2505 2510 2515
tgg aag ggc cgg cgc gta aag cgc gtc ctg cgc ccc ggc acc gcg 16954
Trp Lys Gly Arg Arg Val Lys Arg Val Leu Arg Pro Gly Thr Ala
2520 2525 2530
gtg gtc ttc acg ccc ggc gag cgc tcc acc cgg act ttc aag cgc 16999
Val Val Phe Thr Pro Gly Glu Arg Ser Thr Arg Thr Phe Lys Arg
2535 2540 2545
gtc tat gac gag gtg tac ggc gac gaa gac ctg ctg gag cag gcc 17044
Val Tyr Asp Glu Val Tyr Gly Asp Glu Asp Leu Leu Glu Gln Ala
2550 2555 2560
aac gag cgc ttc gga gag ttt gct tac ggg aag cga cag cgg ccg 17089
Asn Glu Arg Phe Gly Glu Phe Ala Tyr Gly Lys Arg Gln Arg Pro
2565 2570 2575
ctg ggg aag gag gat gag gac ctg ctg gcg ctg ccg ctg gac cgg 17134
Leu Gly Lys Glu Asp Glu Asp Leu Leu Ala Leu Pro Leu Asp Arg
2580 2585 2590
ggc aac ccc acc ccc agc ttg aag ccc gtg acc ctg cag cag gtg 17179
Gly Asn Pro Thr Pro Ser Leu Lys Pro Val Thr Leu Gln Gln Val
2595 2600 2605
ctg ccg agc agc gcg ccc tcc gag acg aag cgg ggt ctg aag cgc 17224
Leu Pro Ser Ser Ala Pro Ser Glu Thr Lys Arg Gly Leu Lys Arg
2610 2615 2620
gag ggc ggc gac ctg gcg ccc acc gtg cag ctg atg gtg ccc aag 17269
Glu Gly Gly Asp Leu Ala Pro Thr Val Gln Leu Met Val Pro Lys
2625 2630 2635
cgg cag agg ctg gag gac gtg ctg gag aaa atg aaa gta gac ccc 17314
Arg Gln Arg Leu Glu Asp Val Leu Glu Lys Met Lys Val Asp Pro
2640 2645 2650
ggt ctg cag ccg gac atc agg gtc cgc ccc atc aag cag gtg gca 17359
Gly Leu Gln Pro Asp Ile Arg Val Arg Pro Ile Lys Gln Val Ala
2655 2660 2665
ccg ggt ctc ggc gtg cag acc gtg gac gtg gtc att ccc acc ggc 17404
Pro Gly Leu Gly Val Gln Thr Val Asp Val Val Ile Pro Thr Gly
2670 2675 2680
aac tcc ccc gcc gcc gcc acc acc acc acc gct acc tcc acg gac 17449
Asn Ser Pro Ala Ala Ala Thr Thr Thr Thr Ala Thr Ser Thr Asp
2685 2690 2695
atg gag acg cag acc gtc ccc gca gcc gca gcc gcc gct gca gcc 17494
Met Glu Thr Gln Thr Val Pro Ala Ala Ala Ala Ala Ala Ala Ala
2700 2705 2710
acc gcc gcg acc tcc tcg gcg gag gtg cag acg gac ccc tgg ctg 17539
Thr Ala Ala Thr Ser Ser Ala Glu Val Gln Thr Asp Pro Trp Leu
2715 2720 2725
ccg ccg gcg atg gct ccc cgc gcg cgc cgc ggg cgc agg aag tac 17584
Pro Pro Ala Met Ala Pro Arg Ala Arg Arg Gly Arg Arg Lys Tyr
2730 2735 2740
ggc gcc gcc aac gcg ctc ctg ccc gag tac gcc ttg cat cct tcc 17629
Gly Ala Ala Asn Ala Leu Leu Pro Glu Tyr Ala Leu His Pro Ser
2745 2750 2755
atc gcg ccc acc ccc ggc tac cga ggc tac acc tac cgc ccg cga 17674
Ile Ala Pro Thr Pro Gly Tyr Arg Gly Tyr Thr Tyr Arg Pro Arg
2760 2765 2770
aga gcc aag ggc tcc acc cgc cgc ccc cgc cga cgc gcc gcc acc 17719
Arg Ala Lys Gly Ser Thr Arg Arg Pro Arg Arg Arg Ala Ala Thr
2775 2780 2785
acc cgc cgc cgt cgc cgc agc cgt cgc cag ccc gca ctg gcc cca 17764
Thr Arg Arg Arg Arg Arg Ser Arg Arg Gln Pro Ala Leu Ala Pro
2790 2795 2800
atc tcc gtg agg aga gtg gcg cgc gac gga cgc acc ctg gtg ctg 17809
Ile Ser Val Arg Arg Val Ala Arg Asp Gly Arg Thr Leu Val Leu
2805 2810 2815
ccc agg gcg cgc tac cac ccc agc atc gtt taaaaagcct gttgtggttc 17859
Pro Arg Ala Arg Tyr His Pro Ser Ile Val
2820 2825
ttgcagat atg gcc ctc act tgc cgc ctc cgt ttc ccg gtg ccg gga 17906
Met Ala Leu Thr Cys Arg Leu Arg Phe Pro Val Pro Gly
2830 2835 2840
tac cga gga gga aga tcg cgc cgc agg agg ggt ctg gcc ggc cgc 17951
Tyr Arg Gly Gly Arg Ser Arg Arg Arg Arg Gly Leu Ala Gly Arg
2845 2850 2855
ggc ctg agc gga ggc agc cgc cgc gcg cac cgg cgg cga cgc gcc 17996
Gly Leu Ser Gly Gly Ser Arg Arg Ala His Arg Arg Arg Arg Ala
2860 2865 2870
acc agc cga cgc atg cgc ggc ggg gtg ctg ccc ctg ctg atc ccc 18041
Thr Ser Arg Arg Met Arg Gly Gly Val Leu Pro Leu Leu Ile Pro
2875 2880 2885
ctg atc gcc gcg gcg atc ggc gcc gtg ccc ggg atc gcc tcc gtg 18086
Leu Ile Ala Ala Ala Ile Gly Ala Val Pro Gly Ile Ala Ser Val
2890 2895 2900
gcc ttg cag gcg tcc cag agg cgt taacagactt gcaaacttgc 18130
Ala Leu Gln Ala Ser Gln Arg Arg
2905 2910
aaatatggaa aaaaaaaaac cccaataaaa aagtctagac tctcacgctc gcttggtcct 18190
gtgactattt tgtaga atg gaa gac atc aac ttt gcg tcg ctg gcc ccg 18239
Met Glu Asp Ile Asn Phe Ala Ser Leu Ala Pro
2915 2920
cgt cac ggc tcg cgc ccg ttc ctg gga cac tgg aac gat atc ggc 18284
Arg His Gly Ser Arg Pro Phe Leu Gly His Trp Asn Asp Ile Gly
2925 2930 2935
acc agc aac atg agc ggt ggc gcc ttc agt tgg ggc tct ctg tgg 18329
Thr Ser Asn Met Ser Gly Gly Ala Phe Ser Trp Gly Ser Leu Trp
2940 2945 2950
agc ggc att aaa agt atc ggg tcg gcc gtt aaa aat tac ggc acc 18374
Ser Gly Ile Lys Ser Ile Gly Ser Ala Val Lys Asn Tyr Gly Thr
2955 2960 2965
cgg gcc tgg aac agc agc acg ggc cag atg ttg aga gac aag ttg 18419
Arg Ala Trp Asn Ser Ser Thr Gly Gln Met Leu Arg Asp Lys Leu
2970 2975 2980
aaa gag cag aac ttc cag cag aag gtg gtg gag ggc ctg gcc tcc 18464
Lys Glu Gln Asn Phe Gln Gln Lys Val Val Glu Gly Leu Ala Ser
2985 2990 2995
ggc atc aac ggg gtg gtg gac ctg gcc aac cag gcc gtg cag aat 18509
Gly Ile Asn Gly Val Val Asp Leu Ala Asn Gln Ala Val Gln Asn
3000 3005 3010
aag atc aac agc aga ctg gac ccc cgg ccg ccg gta gag gag gtg 18554
Lys Ile Asn Ser Arg Leu Asp Pro Arg Pro Pro Val Glu Glu Val
3015 3020 3025
ccg ccg gcg ctg gag acg gtg tcc ccc gat ggg cgg ggc gaa aag 18599
Pro Pro Ala Leu Glu Thr Val Ser Pro Asp Gly Arg Gly Glu Lys
3030 3035 3040
cgc ccg cgg ccc gat agg gaa gag acc act ctg gtc acg cag acc 18644
Arg Pro Arg Pro Asp Arg Glu Glu Thr Thr Leu Val Thr Gln Thr
3045 3050 3055
gat gag ccg ccc ccg tac gag gag gcc ctg aag caa ggt ctg ccc 18689
Asp Glu Pro Pro Pro Tyr Glu Glu Ala Leu Lys Gln Gly Leu Pro
3060 3065 3070
acc acg cgg ccc atc gcg ccc atg gcc acc ggg gtg gtg ggc cgc 18734
Thr Thr Arg Pro Ile Ala Pro Met Ala Thr Gly Val Val Gly Arg
3075 3080 3085
cac acc ccc gcc acg ctg gac ttg cct ccg ccc gcc gat gtg ccg 18779
His Thr Pro Ala Thr Leu Asp Leu Pro Pro Pro Ala Asp Val Pro
3090 3095 3100
cag cag cag aag gcg gca cag ccg ggc ccg ccc gcg acc gcc ccc 18824
Gln Gln Gln Lys Ala Ala Gln Pro Gly Pro Pro Ala Thr Ala Pro
3105 3110 3115
cgt tcc tcc gcc ggt cct ctg cgc cgc gcg gcc agt ggc ccc cgc 18869
Arg Ser Ser Ala Gly Pro Leu Arg Arg Ala Ala Ser Gly Pro Arg
3120 3125 3130
ggc ggg gtc tcg agg cac agc agc ggc aac tgg cag agc acg ctg 18914
Gly Gly Val Ser Arg His Ser Ser Gly Asn Trp Gln Ser Thr Leu
3135 3140 3145
aac agc atc gtg ggt ctg ggg gtg cgg tcc gtg aag cgc cgc cga 18959
Asn Ser Ile Val Gly Leu Gly Val Arg Ser Val Lys Arg Arg Arg
3150 3155 3160
tgc tac tgaatagctt agctaacgtg ttgtatgtgt gtatgcgtcc tatgtcgccg 19015
Cys Tyr
ccagaggagc tgctgagtcg ccgccgttcg cgcgcccacc accgccactc cgcccctcaa 19075
g atg gcg acc cca tcg atg atg ccg cag tgg tcg tac atg cac atc 19121
Met Ala Thr Pro Ser Met Met Pro Gln Trp Ser Tyr Met His Ile
3165 3170 3175
tcg ggc cag gac gcc tcg gag tac ctg agt ccc ggg ctg gtg cag 19166
Ser Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln
3180 3185 3190
ttc gcc cgc gcc acc gag agc tac ttc agt ctg agt aac aag ttt 19211
Phe Ala Arg Ala Thr Glu Ser Tyr Phe Ser Leu Ser Asn Lys Phe
3195 3200 3205
agg aac ccc acg gtg gcg ccc acg cac gat gtg acc acc gac cgg 19256
Arg Asn Pro Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg
3210 3215 3220
tcc cag cgc ctg acg ctg cgg ttc atc ccc gtg gac cgc gag gac 19301
Ser Gln Arg Leu Thr Leu Arg Phe Ile Pro Val Asp Arg Glu Asp
3225 3230 3235
acc gcg tac tcg tac aag gcg cgg ttc acc ctg gcc gtg ggc gac 19346
Thr Ala Tyr Ser Tyr Lys Ala Arg Phe Thr Leu Ala Val Gly Asp
3240 3245 3250
aac cgc gtg ctg gac atg gcc tcc acc tac ttt gac atc cgc ggc 19391
Asn Arg Val Leu Asp Met Ala Ser Thr Tyr Phe Asp Ile Arg Gly
3255 3260 3265
gtg ctg gac cgc ggc ccc acc ttt aag ccc tac tcc ggc acc gcc 19436
Val Leu Asp Arg Gly Pro Thr Phe Lys Pro Tyr Ser Gly Thr Ala
3270 3275 3280
tac aac tcc ctg gcc ccc aag ggc gcg ccc aac cca tgc gag tgg 19481
Tyr Asn Ser Leu Ala Pro Lys Gly Ala Pro Asn Pro Cys Glu Trp
3285 3290 3295
gat gag gct gct act gcc ctt gac att gat ttg aac gca gaa gaa 19526
Asp Glu Ala Ala Thr Ala Leu Asp Ile Asp Leu Asn Ala Glu Glu
3300 3305 3310
gat gaa gaa ggc gat gaa gcc caa ggg gaa gca gat cag cag aaa 19571
Asp Glu Glu Gly Asp Glu Ala Gln Gly Glu Ala Asp Gln Gln Lys
3315 3320 3325
act cat gta ttt ggc cag gcg cca tac tcc gga cag aac att aca 19616
Thr His Val Phe Gly Gln Ala Pro Tyr Ser Gly Gln Asn Ile Thr
3330 3335 3340
aaa gaa ggc ata cag ata ggc att gat gct acc agt caa gcc caa 19661
Lys Glu Gly Ile Gln Ile Gly Ile Asp Ala Thr Ser Gln Ala Gln
3345 3350 3355
aca cct cta tat gcc gac aaa aca ttc caa ccc gaa cct caa atc 19706
Thr Pro Leu Tyr Ala Asp Lys Thr Phe Gln Pro Glu Pro Gln Ile
3360 3365 3370
ggg gag tcc caa tgg aat gag aca gag att agc tat gga gcg gga 19751
Gly Glu Ser Gln Trp Asn Glu Thr Glu Ile Ser Tyr Gly Ala Gly
3375 3380 3385
cgg gtg cta aaa aag acc act ctc atg aaa cct tgc tat ggg tca 19796
Arg Val Leu Lys Lys Thr Thr Leu Met Lys Pro Cys Tyr Gly Ser
3390 3395 3400
tat gca agg cct act aat gag aac gga ggt cag ggc atc ctc ctg 19841
Tyr Ala Arg Pro Thr Asn Glu Asn Gly Gly Gln Gly Ile Leu Leu
3405 3410 3415
gaa caa gat gga aag aaa gaa agt caa gtg gaa atg caa ttt ttc 19886
Glu Gln Asp Gly Lys Lys Glu Ser Gln Val Glu Met Gln Phe Phe
3420 3425 3430
tcc act act cag gca gct gcg ggt aat tca gat aat cct act cca 19931
Ser Thr Thr Gln Ala Ala Ala Gly Asn Ser Asp Asn Pro Thr Pro
3435 3440 3445
aag ctt gtt ttg tac agc gag gat gtt aac ctg gaa aca cca gat 19976
Lys Leu Val Leu Tyr Ser Glu Asp Val Asn Leu Glu Thr Pro Asp
3450 3455 3460
aca cac att tca tac atg ccc act aac aac gaa acc aat tca aga 20021
Thr His Ile Ser Tyr Met Pro Thr Asn Asn Glu Thr Asn Ser Arg
3465 3470 3475
gaa ctg ttg gga caa cag gcc atg ccc aac agg cct aat tac atc 20066
Glu Leu Leu Gly Gln Gln Ala Met Pro Asn Arg Pro Asn Tyr Ile
3480 3485 3490
ggc ttc aga gac aac ttt atc ggt ctc atg tac tac aac agc act 20111
Gly Phe Arg Asp Asn Phe Ile Gly Leu Met Tyr Tyr Asn Ser Thr
3495 3500 3505
ggc aac atg gga gtg ctt gca ggt cag gcc tct cag ttg aat gca 20156
Gly Asn Met Gly Val Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala
3510 3515 3520
gtg gtg gac ttg caa gac aga aac aca gaa ctg tcc tac cag ctc 20201
Val Val Asp Leu Gln Asp Arg Asn Thr Glu Leu Ser Tyr Gln Leu
3525 3530 3535
ttg ctt gat tcc atg ggt gac aga acc aga tat ttc tcc atg tgg 20246
Leu Leu Asp Ser Met Gly Asp Arg Thr Arg Tyr Phe Ser Met Trp
3540 3545 3550
aat cag gca gtg gac agt tat gac cca gat gtt aga att att gaa 20291
Asn Gln Ala Val Asp Ser Tyr Asp Pro Asp Val Arg Ile Ile Glu
3555 3560 3565
aat cat gga acc gaa gac gag ctc ccc aac tat tgt ttt cct ctg 20336
Asn His Gly Thr Glu Asp Glu Leu Pro Asn Tyr Cys Phe Pro Leu
3570 3575 3580
ggc ggc ata atc aat acg gaa act ttt aca aaa gtc aag cct aaa 20381
Gly Gly Ile Ile Asn Thr Glu Thr Phe Thr Lys Val Lys Pro Lys
3585 3590 3595
gct gga cag gac gct cag tgg gaa aaa gat tca gaa ttt tca gat 20426
Ala Gly Gln Asp Ala Gln Trp Glu Lys Asp Ser Glu Phe Ser Asp
3600 3605 3610
aaa aat gaa ata aga gtg gga aac aac ttc gct atg gaa atc aac 20471
Lys Asn Glu Ile Arg Val Gly Asn Asn Phe Ala Met Glu Ile Asn
3615 3620 3625
atc aat gcc aac ctg tgg agg aac ttc ctg tac tcc aac gtg gcc 20516
Ile Asn Ala Asn Leu Trp Arg Asn Phe Leu Tyr Ser Asn Val Ala
3630 3635 3640
ctg tac ctg cca gac aag ctt aag tat act cca tcc aat gtg caa 20561
Leu Tyr Leu Pro Asp Lys Leu Lys Tyr Thr Pro Ser Asn Val Gln
3645 3650 3655
att tcc aac aac ccc aac tcc tac gat tac atg aac aag cga gtg 20606
Ile Ser Asn Asn Pro Asn Ser Tyr Asp Tyr Met Asn Lys Arg Val
3660 3665 3670
gtg gcc ccg ggg ctg gtg gac tgc tac atc aac ctg ggc gcg cgc 20651
Val Ala Pro Gly Leu Val Asp Cys Tyr Ile Asn Leu Gly Ala Arg
3675 3680 3685
tgg tcg ctg gac tac atg gac aac gtc aac ccc ttc aac cac cac 20696
Trp Ser Leu Asp Tyr Met Asp Asn Val Asn Pro Phe Asn His His
3690 3695 3700
cgc aac gcg ggc ctg cgc tac cgc tcc atg ctc ctg ggc aac ggg 20741
Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly
3705 3710 3715
cgc tac gtg ccc ttc cac atc cag gtg ccc cag aag ttc ttt gcc 20786
Arg Tyr Val Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala
3720 3725 3730
atc aag aac ctc ctc ctc ctg ccg ggc tcc tac acc tac gag tgg 20831
Ile Lys Asn Leu Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp
3735 3740 3745
aac ttc agg aag gat gtc aac atg gtc ctc cag agc tct ctg ggc 20876
Asn Phe Arg Lys Asp Val Asn Met Val Leu Gln Ser Ser Leu Gly
3750 3755 3760
aac gat ctc agg gtg gac ggg gcc agc atc aag ttc gag agc atc 20921
Asn Asp Leu Arg Val Asp Gly Ala Ser Ile Lys Phe Glu Ser Ile
3765 3770 3775
tgc ctc tac gcc acc ttc ttc ccc atg gcc cac aac acc gcc tcc 20966
Cys Leu Tyr Ala Thr Phe Phe Pro Met Ala His Asn Thr Ala Ser
3780 3785 3790
acg ctc gag gcc atg ctc agg aac gac acc aac gac cag tcc ttc 21011
Thr Leu Glu Ala Met Leu Arg Asn Asp Thr Asn Asp Gln Ser Phe
3795 3800 3805
aat gac tac ctc tcc gcc gcc aac atg ctc tac ccc atc ccc gcc 21056
Asn Asp Tyr Leu Ser Ala Ala Asn Met Leu Tyr Pro Ile Pro Ala
3810 3815 3820
aac gcc acc aac gtc ccc atc tcc atc ccc tcg cgc aac tgg gcg 21101
Asn Ala Thr Asn Val Pro Ile Ser Ile Pro Ser Arg Asn Trp Ala
3825 3830 3835
gcc ttc cgc ggc tgg gcc ttc acc cgc ctc aag acc aag gag acc 21146
Ala Phe Arg Gly Trp Ala Phe Thr Arg Leu Lys Thr Lys Glu Thr
3840 3845 3850
ccc tcc ctg ggc tcg gga ttc gac ccc tac tac acc tac tcg gga 21191
Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr Tyr Thr Tyr Ser Gly
3855 3860 3865
tcc att ccc tac ctg gac ggc acc ttc tac ctc aac cac act ttc 21236
Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu Asn His Thr Phe
3870 3875 3880
aag aag gtc tcg gtc acc ttc gac tcc tcg gtc agc tgg ccg ggc 21281
Lys Lys Val Ser Val Thr Phe Asp Ser Ser Val Ser Trp Pro Gly
3885 3890 3895
aac gac cgc ctg ctc acc ccc aac gag ttc gag atc aag cgc tcg 21326
Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys Arg Ser
3900 3905 3910
gtc gac ggg gag ggc tac aac gtg gcc cag tgc aac atg acc aag 21371
Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr Lys
3915 3920 3925
gac tgg ttc ctg gtc cag atg ctg gcc aac tac aac atc ggc tac 21416
Asp Trp Phe Leu Val Gln Met Leu Ala Asn Tyr Asn Ile Gly Tyr
3930 3935 3940
cag ggc ttc tac atc cca gag agc tac aag gac agg atg tac tcc 21461
Gln Gly Phe Tyr Ile Pro Glu Ser Tyr Lys Asp Arg Met Tyr Ser
3945 3950 3955
ttc ttc agg aac ttc cag ccc atg agc cgg cag gtg gtg gac cag 21506
Phe Phe Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp Gln
3960 3965 3970
acc aag tac aag gac tac cag gag gtg ggc atc atc cac cag cac 21551
Thr Lys Tyr Lys Asp Tyr Gln Glu Val Gly Ile Ile His Gln His
3975 3980 3985
aac aac tcg ggc ttc gtg ggc tac ctt gcc ccc acc atg cgc gag 21596
Asn Asn Ser Gly Phe Val Gly Tyr Leu Ala Pro Thr Met Arg Glu
3990 3995 4000
gga cag gcc tac ccc gcc aac ttc ccc tac ccg ctc ata ggc aag 21641
Gly Gln Ala Tyr Pro Ala Asn Phe Pro Tyr Pro Leu Ile Gly Lys
4005 4010 4015
acc gcg gtc gac agc atc acc cag aaa aag ttc ctc tgc gac cgc 21686
Thr Ala Val Asp Ser Ile Thr Gln Lys Lys Phe Leu Cys Asp Arg
4020 4025 4030
acc ctc tgg cgc atc ccc ttc tcc agc aac ttc atg tcc atg ggt 21731
Thr Leu Trp Arg Ile Pro Phe Ser Ser Asn Phe Met Ser Met Gly
4035 4040 4045
gcg ctc acg gac ctg ggc cag aac ctg ctc tat gcc aac tcc gcc 21776
Ala Leu Thr Asp Leu Gly Gln Asn Leu Leu Tyr Ala Asn Ser Ala
4050 4055 4060
cac gcg ctc gac atg acc ttc gag gtc gac ccc atg gac gag ccc 21821
His Ala Leu Asp Met Thr Phe Glu Val Asp Pro Met Asp Glu Pro
4065 4070 4075
acc ctt ctc tat gtt ctg ttc gaa gtc ttt gac gtg gtc cgg gtc 21866
Thr Leu Leu Tyr Val Leu Phe Glu Val Phe Asp Val Val Arg Val
4080 4085 4090
cac cag ccg cac cgc ggc gtc atc gag acc gtg tac ctg cgc aca 21911
His Gln Pro His Arg Gly Val Ile Glu Thr Val Tyr Leu Arg Thr
4095 4100 4105
ccc ttc tcg gcc ggc aac gcc acc acc taaagaagca agccgccgcc 21958
Pro Phe Ser Ala Gly Asn Ala Thr Thr
4110 4115
tccgccgccg cccgc atg ccg tcg ggt tcc acc gag cag gag ctc agg 22006
Met Pro Ser Gly Ser Thr Glu Gln Glu Leu Arg
4120 4125
gcc atc gtc aga gac ctg gga tgc ggg ccc tat ttt ttg ggc acc 22051
Ala Ile Val Arg Asp Leu Gly Cys Gly Pro Tyr Phe Leu Gly Thr
4130 4135 4140
ttc gac aag cgc ttc ccg ggc ttc gtc tcc ccg cac aag ctg gcc 22096
Phe Asp Lys Arg Phe Pro Gly Phe Val Ser Pro His Lys Leu Ala
4145 4150 4155
tgc gcc atc gtc aac acg gcc ggc cgc gag acc ggg ggc gtg cac 22141
Cys Ala Ile Val Asn Thr Ala Gly Arg Glu Thr Gly Gly Val His
4160 4165 4170
tgg ctg gcc ttc gcc tgg aac ccg cgc tcc aaa aca tgc ttt ctc 22186
Trp Leu Ala Phe Ala Trp Asn Pro Arg Ser Lys Thr Cys Phe Leu
4175 4180 4185
ttt gac ccc ttc ggc ttc tcg gac cag cgg ctc aag cag atc tac 22231
Phe Asp Pro Phe Gly Phe Ser Asp Gln Arg Leu Lys Gln Ile Tyr
4190 4195 4200
gag ttc gag tac gag ggc ctg ctg cgt cgc agc gcc atc gcc tcc 22276
Glu Phe Glu Tyr Glu Gly Leu Leu Arg Arg Ser Ala Ile Ala Ser
4205 4210 4215
tcg ccc gac cgc tgc gtc acc ctg gag aag tcc acc caa acc gtg 22321
Ser Pro Asp Arg Cys Val Thr Leu Glu Lys Ser Thr Gln Thr Val
4220 4225 4230
cag ggg ccc gac tcg gcc gcc tgc ggt ctc ttt tgc tgc atg ttc 22366
Gln Gly Pro Asp Ser Ala Ala Cys Gly Leu Phe Cys Cys Met Phe
4235 4240 4245
ctg cac gcc ttc gtg cac tgg ccc cag agt ccc atg gac cgc aac 22411
Leu His Ala Phe Val His Trp Pro Gln Ser Pro Met Asp Arg Asn
4250 4255 4260
ccc acc atg aac ttg ctg acg ggg gtg ccc aac tcc atg ctc cag 22456
Pro Thr Met Asn Leu Leu Thr Gly Val Pro Asn Ser Met Leu Gln
4265 4270 4275
agc ccc cag gtc gag ccc acc ctg cgc cgc aac cag gag cag ctc 22501
Ser Pro Gln Val Glu Pro Thr Leu Arg Arg Asn Gln Glu Gln Leu
4280 4285 4290
tac agc ttc ctg gag cgc cac tcg ccc tac ttc cgc cgc cac agc 22546
Tyr Ser Phe Leu Glu Arg His Ser Pro Tyr Phe Arg Arg His Ser
4295 4300 4305
gca cag atc agg agg gcc acc tcc ttc tgc cac ttg caa gag atg 22591
Ala Gln Ile Arg Arg Ala Thr Ser Phe Cys His Leu Gln Glu Met
4310 4315 4320
caa gaa ggg aaa taataacgat gtacacactt ttttctctca ataaatggca 22643
Gln Glu Gly Lys
4325
tttttttatt tatacatgct ctctggggta ttcatttccc aaccaccacc tccacccgcc 22703
gccgccgcca tctggctctc tttagaaatc gaaagggttc tgccgggagt cgccgtgcgc 22763
cacgggcagg gacacgttgc ggtactggta gcgggtgccc cacttgaact cgggcaccac 22823
caggcgaggt agctcgggga agttttcgtt ccacaggctg cgggtcagca ccagcgcgtt 22883
catcaggtcg ggcgccgaga tcttgaagtc gcagttgggg ccggcgccct gcgcgcgcga 22943
gttgcggtac accgggttgc agcactggaa caccagcagc gccgggtact tcacgctggc 23003
cagcacgctg cggtcggaga tcagctcggc gtccaggtcc tccgcgttgc tcagcgcgaa 23063
cggggtcatc ttgggcacct gccgccccag gaagggcgca tgccccggtt tcgagttgca 23123
gtcgcagcgc agcgggatca gcaggtgccc gtgcccggac tcggcgttgg ggtacagcgc 23183
gcgcaggaag gcctgcatct ggcggaaggc catctgggcc ttcgcgccct ccgagaagaa 23243
catgccgcag gatttgcccg agaactggtt cgcggggcag ctcgcgtcgt gcaggcaaca 23303
gcgcgcgtcg gtgttggcga tctgcaccac gttgcgcccc caccggttct tcacgatctt 23363
ggccttggac gcctgctcct tcagcgcgcg ctgcccgttc tcgctggtca catccatctc 23423
gatcacatgc tccttgttca ccatgctgct gccgtgcagg cacttcagct cgccctccgt 23483
ctcagtgcag cggtgctgcc acagcgcgca gcccgtgggc tcgaaagact tgtaggtcac 23543
ctccgcgaag gactgcaggt acccctgcaa aaagcgcccc atcatggtca cgaaggtctt 23603
gttgctgctg aaggtcagct gcagcccgcg gtgctcctcg ttcagccagg tcttgcaaac 23663
ggccgccagc gcctccacct ggtcgggcag catcttgaag ttcaccttca gctcattctc 23723
cacgtggtac ttgtccatca gcgcgcgcgc cgcctccata cccttctccc aggccgacac 23783
cagcggcagg ctcatggggt tcttcaccat cgccgtggcc gccgccgccg cggccccctc 23843
cgccgcgctt tcgctttccg ccccgctgtt ctcttcctct tcctcctctt cctcctcgtc 23903
gccgccgccc actcgcagcc cccgcactag ggggtcgtct tcctgcaggc gctgcacctt 23963
gcgcttgccg ccgcgcccct gcttgatgcg cacgggcggg ttgctgaagc ccaccattac 24023
cagcgcggcc tcttcttgct cttcctcgct gtccagaatg acctccgggg agggggggct 24083
ggccatcctc agtaccgagg cacgcttctt tttcttcctg ggggcgtttg ccagctccgc 24143
ggctgcggcc gccgccgagg tcgaaggccg agggctgggc gtgcgcggca ccagcgcgtc 24203
ctgcgagccg tcctcgtcct cctcggactc gaggcggcag cgggcccgct tctttggggg 24263
cgcgcggggc ggcggcggcg gaggcggcga cggagacggg gacgagacat cgtccagggt 24323
gggtggacgg cgggccgcgc cgcgtccgcg ctcgggggtg gtctcgcgct ggtcctcttc 24383
ccgactggcc atctcccact gctccttctc ctataggcag aaagagatc atg gag 24438
Met Glu
tct ctc atg caa gtc gag aag gag gag gac agc cta acc gcc ccc 24483
Ser Leu Met Gln Val Glu Lys Glu Glu Asp Ser Leu Thr Ala Pro
4330 4335 4340
tct gag ccc acc acc gcc gcc acc gcc gcc gcc agt gcc gcc gcg 24528
Ser Glu Pro Thr Thr Ala Ala Thr Ala Ala Ala Ser Ala Ala Ala
4345 4350 4355
gac gac gcg ccc acc gag acc acc acc act acc acc acc ctt ccc 24573
Asp Asp Ala Pro Thr Glu Thr Thr Thr Thr Thr Thr Thr Leu Pro
4360 4365 4370
agc gac gca ccc ccg ctc gag aag gaa gtg ctg atc gag cag gac 24618
Ser Asp Ala Pro Pro Leu Glu Lys Glu Val Leu Ile Glu Gln Asp
4375 4380 4385
ccg ggt ttt gtg agc gaa gag gag gat gag gcg gat gag aag gag 24663
Pro Gly Phe Val Ser Glu Glu Glu Asp Glu Ala Asp Glu Lys Glu
4390 4395 4400
gat act gcc gcc tca gtg cca aaa gag gat aaa aag caa gac cag 24708
Asp Thr Ala Ala Ser Val Pro Lys Glu Asp Lys Lys Gln Asp Gln
4405 4410 4415
gac gac gca gaa aaa gat gag gca gca gtc ggg cgg ggg gac gga 24753
Asp Asp Ala Glu Lys Asp Glu Ala Ala Val Gly Arg Gly Asp Gly
4420 4425 4430
agc cat gat gct gat gac ggc tac cta gac gtg gga gac gac gtg 24798
Ser His Asp Ala Asp Asp Gly Tyr Leu Asp Val Gly Asp Asp Val
4435 4440 4445
ctg ctt aag cac ctg cac cgc cag tgc gtc atc atc tgc gac gcg 24843
Leu Leu Lys His Leu His Arg Gln Cys Val Ile Ile Cys Asp Ala
4450 4455 4460
ctg cag gag cgc tgc gaa gtg ccc ctg gac gtg gcg gag gtc agc 24888
Leu Gln Glu Arg Cys Glu Val Pro Leu Asp Val Ala Glu Val Ser
4465 4470 4475
cgc gcc tac gag cgg cac ctc ttc gcg ccg cac gtg ccc ccc aag 24933
Arg Ala Tyr Glu Arg His Leu Phe Ala Pro His Val Pro Pro Lys
4480 4485 4490
cgc cgc gag aac ggc acc tgc gag ccc aac ccg cgc ctc aac ttc 24978
Arg Arg Glu Asn Gly Thr Cys Glu Pro Asn Pro Arg Leu Asn Phe
4495 4500 4505
tac ccg gtc ttc gcg gta ccc gag gtg ctg gcc acc tac cac atc 25023
Tyr Pro Val Phe Ala Val Pro Glu Val Leu Ala Thr Tyr His Ile
4510 4515 4520
ttc ttc caa aac tgc aag atc ccc ctc tcc tgc cgc gcc aac cgc 25068
Phe Phe Gln Asn Cys Lys Ile Pro Leu Ser Cys Arg Ala Asn Arg
4525 4530 4535
acc cgc gcc gac aag acc ctg acc atg cgc cag ggc gcc cac ata 25113
Thr Arg Ala Asp Lys Thr Leu Thr Met Arg Gln Gly Ala His Ile
4540 4545 4550
cct gat atc acc tct ctg gag gaa gtg ccc aag atc ttc gag ggt 25158
Pro Asp Ile Thr Ser Leu Glu Glu Val Pro Lys Ile Phe Glu Gly
4555 4560 4565
ctc ggt cgc gac gag aaa cgg gcg gcg aac gct ctg cac gga gac 25203
Leu Gly Arg Asp Glu Lys Arg Ala Ala Asn Ala Leu His Gly Asp
4570 4575 4580
agt gaa aac gag agt cac tcg ggg gtg ctg gtg gag ctc gag ggc 25248
Ser Glu Asn Glu Ser His Ser Gly Val Leu Val Glu Leu Glu Gly
4585 4590 4595
gac aac gcg cgc ctg gcc gtg ctc aag cgc agc atc gag gtc acc 25293
Asp Asn Ala Arg Leu Ala Val Leu Lys Arg Ser Ile Glu Val Thr
4600 4605 4610
cac ttc gcc tac ccg gcg ctc aac ctg ccc ccc aag gtc atg agt 25338
His Phe Ala Tyr Pro Ala Leu Asn Leu Pro Pro Lys Val Met Ser
4615 4620 4625
gtg gtc atg ggc gag ctc atc atg cgc cgc gcc cag ccc ctg gac 25383
Val Val Met Gly Glu Leu Ile Met Arg Arg Ala Gln Pro Leu Asp
4630 4635 4640
gcg gat gca aac ttg caa gag tcc tcc gag gaa ggc ctg ccc gcg 25428
Ala Asp Ala Asn Leu Gln Glu Ser Ser Glu Glu Gly Leu Pro Ala
4645 4650 4655
gtc agc gac gag cag ctg gcg cgc tgg ctg gag acc cgc gac ccc 25473
Val Ser Asp Glu Gln Leu Ala Arg Trp Leu Glu Thr Arg Asp Pro
4660 4665 4670
gcg cag ctg gag gag cgg cgc aag ctc atg atg gcc gcg gtg ctg 25518
Ala Gln Leu Glu Glu Arg Arg Lys Leu Met Met Ala Ala Val Leu
4675 4680 4685
gtc acc gtg gag ctc gag tgt ctg cag cgc ttc ttc gcc gac ccc 25563
Val Thr Val Glu Leu Glu Cys Leu Gln Arg Phe Phe Ala Asp Pro
4690 4695 4700
gag atg cag cgc aag ctc gag gag acc ctg cac tac acc ttc cgc 25608
Glu Met Gln Arg Lys Leu Glu Glu Thr Leu His Tyr Thr Phe Arg
4705 4710 4715
cag ggc tac gtg cgc cag gcc tgc aag atc tcc aac gtg gag ctc 25653
Gln Gly Tyr Val Arg Gln Ala Cys Lys Ile Ser Asn Val Glu Leu
4720 4725 4730
tgc aac ctg gtc tcc tac ctg ggc atc ctg cac gag aac cgc ctc 25698
Cys Asn Leu Val Ser Tyr Leu Gly Ile Leu His Glu Asn Arg Leu
4735 4740 4745
ggg cag aac gtc ctg cac tcc acc ctc cga ggg gag gcg cgc cgc 25743
Gly Gln Asn Val Leu His Ser Thr Leu Arg Gly Glu Ala Arg Arg
4750 4755 4760
gat tac atc cgc gac tgc gtc tac ctc ttt ctc tgc tac acc tgg 25788
Asp Tyr Ile Arg Asp Cys Val Tyr Leu Phe Leu Cys Tyr Thr Trp
4765 4770 4775
cag acg gcc atg ggg gtc tgg cag cag tgc ctg gag gag cgc aac 25833
Gln Thr Ala Met Gly Val Trp Gln Gln Cys Leu Glu Glu Arg Asn
4780 4785 4790
ctc aag gag ctg gaa aag ctc ctc agg cgc gcc ctc agg gac ctc 25878
Leu Lys Glu Leu Glu Lys Leu Leu Arg Arg Ala Leu Arg Asp Leu
4795 4800 4805
tgg acg ggc ttc aac gag cgc tcg gtg gcc gcc gcg ctg gcg gac 25923
Trp Thr Gly Phe Asn Glu Arg Ser Val Ala Ala Ala Leu Ala Asp
4810 4815 4820
atc atc ttc ccc gag cgt ctg ctc aag acc ctg caa cag ggc ctg 25968
Ile Ile Phe Pro Glu Arg Leu Leu Lys Thr Leu Gln Gln Gly Leu
4825 4830 4835
ccc gac ttc acc agc cag agc atg ctg cag aac ttc agg act ttc 26013
Pro Asp Phe Thr Ser Gln Ser Met Leu Gln Asn Phe Arg Thr Phe
4840 4845 4850
atc ctg gag cgc tcg ggc atc ctg ccg gcc acc tgc tgc gcg ctg 26058
Ile Leu Glu Arg Ser Gly Ile Leu Pro Ala Thr Cys Cys Ala Leu
4855 4860 4865
ccc agc gac ttc gtg ccc atc aag tac agg gag tgc ccg ccg ccg 26103
Pro Ser Asp Phe Val Pro Ile Lys Tyr Arg Glu Cys Pro Pro Pro
4870 4875 4880
ctc tgg ggc cac tgc tac ctc ttc cag ctg gcc aac tac ctc gcc 26148
Leu Trp Gly His Cys Tyr Leu Phe Gln Leu Ala Asn Tyr Leu Ala
4885 4890 4895
cac cac tcg gac ctc atg gaa gac gtg agc ggc gag ggc ctg ctc 26193
His His Ser Asp Leu Met Glu Asp Val Ser Gly Glu Gly Leu Leu
4900 4905 4910
gag tgc cac tgc cgc tgc aac ctc tgc acg ccc cac cgc tct ctg 26238
Glu Cys His Cys Arg Cys Asn Leu Cys Thr Pro His Arg Ser Leu
4915 4920 4925
gtc tgc aac ccg cag ctg ctc agc gag agt cag att atc ggt acc 26283
Val Cys Asn Pro Gln Leu Leu Ser Glu Ser Gln Ile Ile Gly Thr
4930 4935 4940
ttc gag ctg cag ggt ccc tcg cct gac gag aag tcc gcg gct ccg 26328
Phe Glu Leu Gln Gly Pro Ser Pro Asp Glu Lys Ser Ala Ala Pro
4945 4950 4955
ggg ctg aaa ctc act ccg ggg ctg tgg act tcc gcc tac cta cgc 26373
Gly Leu Lys Leu Thr Pro Gly Leu Trp Thr Ser Ala Tyr Leu Arg
4960 4965 4970
aaa ttt gta cct gag gac tac cac gcc cac gag atc agg ttc tac 26418
Lys Phe Val Pro Glu Asp Tyr His Ala His Glu Ile Arg Phe Tyr
4975 4980 4985
gaa gac caa tcc cgc ccg ccc aag gcg gag ctc acc gcc tgc gtc 26463
Glu Asp Gln Ser Arg Pro Pro Lys Ala Glu Leu Thr Ala Cys Val
4990 4995 5000
atc acc cag ggg cac atc ctg ggc caa ttg caa gcc atc aac aaa 26508
Ile Thr Gln Gly His Ile Leu Gly Gln Leu Gln Ala Ile Asn Lys
5005 5010 5015
gcc cgc caa gag ttc ttg ctg aaa aag ggt cgg ggg gtg tac ctg 26553
Ala Arg Gln Glu Phe Leu Leu Lys Lys Gly Arg Gly Val Tyr Leu
5020 5025 5030
gac ccc cag tcc ggc gag gag ctc aac ccg cta ccc ccg ccg ccg 26598
Asp Pro Gln Ser Gly Glu Glu Leu Asn Pro Leu Pro Pro Pro Pro
5035 5040 5045
ccc cag cag cgg gac ctt gct tcc cag gat ggc acc cag aaa gaa 26643
Pro Gln Gln Arg Asp Leu Ala Ser Gln Asp Gly Thr Gln Lys Glu
5050 5055 5060
gca gca gca gcc gcc gcc gca gcc tca gcc cta cat gct tct gga 26688
Ala Ala Ala Ala Ala Ala Ala Ala Ser Ala Leu His Ala Ser Gly
5065 5070 5075
gga aga gga gga ctg gga cag tca ggc aga gga ggt ttc gga cga 26733
Gly Arg Gly Gly Leu Gly Gln Ser Gly Arg Gly Gly Phe Gly Arg
5080 5085 5090
gga gga gga gat gat gga aga ctg gga gga gga cag cag cct aga 26778
Gly Gly Gly Asp Asp Gly Arg Leu Gly Gly Gly Gln Gln Pro Arg
5095 5100 5105
cga gga agc ttc aga ggc cga aga ggt ggc aga cgc aac acc atc 26823
Arg Gly Ser Phe Arg Gly Arg Arg Gly Gly Arg Arg Asn Thr Ile
5110 5115 5120
acc ctc ggt cgc agc ccc ctc gcc ggg gcc cct gaa gtc ctc cga 26868
Thr Leu Gly Arg Ser Pro Leu Ala Gly Ala Pro Glu Val Leu Arg
5125 5130 5135
gcc cag cat cag cgc tat aac ctc cgc tcc tcc ggc gcc acc cgg 26913
Ala Gln His Gln Arg Tyr Asn Leu Arg Ser Ser Gly Ala Thr Arg
5140 5145 5150
ccg cag acc caa ccg tagatgggac accacaggaa ccggggtcgg taagtcaaag 26968
Pro Gln Thr Gln Pro
5155
tgcccaccgc cgccaccccc ctcgcagcag cagcgccagg gctaccgctc gtggcgcggg 27028
cacaagaacg ccatagtcgc ctgcttgcaa gactgcgggg gcaacatctc cttcgcccgc 27088
cgcttcctgc tcttccacca cggggtcgcc ttcccccgca atgtcctgca ttactaccgt 27148
catctctaca gcccctactg cggcagcggc gacccagagg cggcagcgtc agccgcagcg 27208
gagaccacca gctaggaaga cctcatcctc cgcgggcaag acggcggcag cggccaggag 27268
acccgcggcg gctgcggcga cgggagcggt gggcgcactg cgcctctcgc ccaacgaacc 27328
cctctcgacc cgggagctca gacacaggat cttccccact ctgtatgcca tcttccaaca 27388
gagcagaggc caggagcagg agctgaaaat aaaaaacaga tctctgcgct ccctcacccg 27448
cagctgtctg tatcacaaaa gcgaagatca gcttcggcgc acgctagagg acgcggaggc 27508
actcttcagc aaatactgcg cgctcactct taaggactag ctccgcgccc ttctcgaatt 27568
taggcgggag aaaactacgt catcgccggc cgccgcccag cccgcccagc cgac atg 27625
Met
5160
agc aaa gag att ccc acg cca tac atg tgg agc tac cag ccg cag 27670
Ser Lys Glu Ile Pro Thr Pro Tyr Met Trp Ser Tyr Gln Pro Gln
5165 5170 5175
atg gga gtc gcg gcg gga gcg gcc cag gac tac tcc acc cgc atg 27715
Met Gly Val Ala Ala Gly Ala Ala Gln Asp Tyr Ser Thr Arg Met
5180 5185 5190
aac tac atg agc gcg gga ccc cac atg atc tca cgg gtc aac ggt 27760
Asn Tyr Met Ser Ala Gly Pro His Met Ile Ser Arg Val Asn Gly
5195 5200 5205
atc cgc gcc cag cga aac caa ata ctg ctg gaa cag gcg gcc atc 27805
Ile Arg Ala Gln Arg Asn Gln Ile Leu Leu Glu Gln Ala Ala Ile
5210 5215 5220
acc gcc acg ccc cgt cat aat ctc aac ccc cga aat tgg ccc gcc 27850
Thr Ala Thr Pro Arg His Asn Leu Asn Pro Arg Asn Trp Pro Ala
5225 5230 5235
gcc ctc gtg tac cag gaa acc ccc tct gcc acc acc gta cta ctt 27895
Ala Leu Val Tyr Gln Glu Thr Pro Ser Ala Thr Thr Val Leu Leu
5240 5245 5250
ccg cgt gac gcc cag gcc gaa gtc cag atg act aac tca ggg gcg 27940
Pro Arg Asp Ala Gln Ala Glu Val Gln Met Thr Asn Ser Gly Ala
5255 5260 5265
cag ctc gcg ggc ggc ttt cgt cac ggg gcg agg ccg cac cgg cag 27985
Gln Leu Ala Gly Gly Phe Arg His Gly Ala Arg Pro His Arg Gln
5270 5275 5280
ggt ata tta cac ctg gcg atc aga ggc cga ggt att cag ctc aac 28030
Gly Ile Leu His Leu Ala Ile Arg Gly Arg Gly Ile Gln Leu Asn
5285 5290 5295
gac gag tcg gtg agc tct tcg ctc ggt ctc cgt ccg gac gga acc 28075
Asp Glu Ser Val Ser Ser Ser Leu Gly Leu Arg Pro Asp Gly Thr
5300 5305 5310
ttc cag ctc gcc gga gcc ggc cgc tct tcg ttc acg ccc cgc cag 28120
Phe Gln Leu Ala Gly Ala Gly Arg Ser Ser Phe Thr Pro Arg Gln
5315 5320 5325
gcg tac ctg act ctg cag acc tcg tcc tcg gag cct cgc tcc ggc 28165
Ala Tyr Leu Thr Leu Gln Thr Ser Ser Ser Glu Pro Arg Ser Gly
5330 5335 5340
ggc atc ggg acc ctc cag ttc gtg gag gag ttc gtg ccc tcg gtc 28210
Gly Ile Gly Thr Leu Gln Phe Val Glu Glu Phe Val Pro Ser Val
5345 5350 5355
tac ttc aac ccc ttc tcg gga cct ccc gga cgc tac ccc gac cag 28255
Tyr Phe Asn Pro Phe Ser Gly Pro Pro Gly Arg Tyr Pro Asp Gln
5360 5365 5370
ttc atc ccg aac ttt gac gcg gtg aag gac tca gcg gac ggc tac 28300
Phe Ile Pro Asn Phe Asp Ala Val Lys Asp Ser Ala Asp Gly Tyr
5375 5380 5385
gac tga atg tca ggt gcc gag gca gag cgg ctt cgc ctg aaa cac 28345
Asp Met Ser Gly Ala Glu Ala Glu Arg Leu Arg Leu Lys His
5390 5395
ctc gag cac tgc cgc cgc cac aac tgc ttc gcc cgc ggc tcc ggt 28390
Leu Glu His Cys Arg Arg His Asn Cys Phe Ala Arg Gly Ser Gly
5400 5405 5410
gag ttc tgc tac ttt cag cta ccc gag gag cat acc gaa ggg ccg 28435
Glu Phe Cys Tyr Phe Gln Leu Pro Glu Glu His Thr Glu Gly Pro
5415 5420 5425
gcg cac ggc gtc cgc ctg acc acc cag ggc gag gtt acc tgt tcc 28480
Ala His Gly Val Arg Leu Thr Thr Gln Gly Glu Val Thr Cys Ser
5430 5435 5440
ctc atc cgg gag ttc acc ctc cgt ccc ctg cta gtg gag cgg gag 28525
Leu Ile Arg Glu Phe Thr Leu Arg Pro Leu Leu Val Glu Arg Glu
5445 5450 5455
cgg ggt ccc tgt gtc cta act atc gcc tgc aac tgc cct aac cct 28570
Arg Gly Pro Cys Val Leu Thr Ile Ala Cys Asn Cys Pro Asn Pro
5460 5465 5470
gga tta cat caa gat ctt tgc tgt cat ctc tgt gct gag ttt aat 28615
Gly Leu His Gln Asp Leu Cys Cys His Leu Cys Ala Glu Phe Asn
5475 5480 5485
aaa cgc tgagatcaga atctactggg gctcctgtcg ccatcctctg aacgccaccg 28671
Lys Arg
5490
tcttcaccca ccccgaccag gcccaggcga acctcacctg cggtctgcat cggagggcca 28731
ggaagtacct cacctggtac ttcaacggca ccccctttgt ggtttacaac agcttcgacg 28791
gggacggagt ctccctgaaa gaccagctct ccggtctcag ctactccatc cacaagaaca 28851
ccaccctcca actcttccct ccctacctgc cgggaaccta cgagtgcgtc accggccgct 28911
gcacccacct cacccgcctg atcgtaaacc agagctttcc gggaacagat aactccctct 28971
tccccagaac aggaggtgag ctcaggaaac tccccgggga ccagggcgga gacctacctt 29031
cgacccttgt ggggttagga ttttttatta ccgggttgct ggctgtttta atcaaagctt 29091
ccttgagatt tatcctctcc atttacgtgt atgaacacct cagcctccag taactctacc 29151
ctttcttcgg aatcaggtga cttttctgaa atcgggctcg gtgtgctgct tactctgttg 29211
atttttttcc ttatcatact cagccttctg tgcctcaggc tcgccgcctg ctgcgcacat 29271
atctacatct actgctggtt gctcaagtgc aggggtcgcc acccaag atg aac agg 29327
Met Asn Arg
tac aca att cta acc atc cta ggc ctg ctg gcc ctg gcg gcc tgc 29372
Tyr Thr Ile Leu Thr Ile Leu Gly Leu Leu Ala Leu Ala Ala Cys
5495 5500 5505
agc gcc gcc acc aaa aaa gag gtt acc ttt gag gag ccc gct tgc 29417
Ser Ala Ala Thr Lys Lys Glu Val Thr Phe Glu Glu Pro Ala Cys
5510 5515 5520
aat gta acc ttc aag ccc gag ggt gcg cat tgt acc acc ctg gtc 29462
Asn Val Thr Phe Lys Pro Glu Gly Ala His Cys Thr Thr Leu Val
5525 5530 5535
aaa tgc gtt acc aag cat gag agg ttg cgc atc gac tac aaa aac 29507
Lys Cys Val Thr Lys His Glu Arg Leu Arg Ile Asp Tyr Lys Asn
5540 5545 5550
atg act ggc agg tat gcg gtc tat agt atc ttt acg ccc gga gac 29552
Met Thr Gly Arg Tyr Ala Val Tyr Ser Ile Phe Thr Pro Gly Asp
5555 5560 5565
ccc tct aac tac tct gtc acc gtc ttt gag ggc ggt cag ttt aag 29597
Pro Ser Asn Tyr Ser Val Thr Val Phe Glu Gly Gly Gln Phe Lys
5570 5575 5580
aaa ttc gat tac act ttc ccc ttt tat gag ttg tgc gat gcg gtc 29642
Lys Phe Asp Tyr Thr Phe Pro Phe Tyr Glu Leu Cys Asp Ala Val
5585 5590 5595
atg tac atg tca aaa cag tac aac ctg tgg ccc ccc act ccc cag 29687
Met Tyr Met Ser Lys Gln Tyr Asn Leu Trp Pro Pro Thr Pro Gln
5600 5605 5610
gcg tgt gtg gaa aat act ggg tct ttc tgc tgt gtg gct ttc cta 29732
Ala Cys Val Glu Asn Thr Gly Ser Phe Cys Cys Val Ala Phe Leu
5615 5620 5625
atc act gca gtc gct cta atc tgc acg ctg cta tat atc aaa ttc 29777
Ile Thr Ala Val Ala Leu Ile Cys Thr Leu Leu Tyr Ile Lys Phe
5630 5635 5640
agg cag agg cga atc ttt atc gat gaa aag aaa atg cct tgatcgctaa 29826
Arg Gln Arg Arg Ile Phe Ile Asp Glu Lys Lys Met Pro
5645 5650 5655
caccggcttt ctatctgcag a atg aat gca atc acc acc tcc cta cta atc 29877
Met Asn Ala Ile Thr Thr Ser Leu Leu Ile
5660 5665
acc acc acc ctc ctt gcg att gcc cat ggg ttg aca cga atc gaa 29922
Thr Thr Thr Leu Leu Ala Ile Ala His Gly Leu Thr Arg Ile Glu
5670 5675 5680
gtg cca gtg ggg tcc aat gtc acc atg gtg ggc ccc gcc ggc aat 29967
Val Pro Val Gly Ser Asn Val Thr Met Val Gly Pro Ala Gly Asn
5685 5690 5695
tcc acc ctc atg tgg gaa aaa ttt gtc cgc aat caa tgg gtt cat 30012
Ser Thr Leu Met Trp Glu Lys Phe Val Arg Asn Gln Trp Val His
5700 5705 5710
ttc tgc tct aac cga atc agt atc aag ccc aga gcc atc tgc gat 30057
Phe Cys Ser Asn Arg Ile Ser Ile Lys Pro Arg Ala Ile Cys Asp
5715 5720 5725
ggg caa aat cta acc ctg atc gat gtg caa atg atg gat gcc ggg 30102
Gly Gln Asn Leu Thr Leu Ile Asp Val Gln Met Met Asp Ala Gly
5730 5735 5740
tac tat tac ggg cag cgg gga gag att att aat tac tgg cga ccc 30147
Tyr Tyr Tyr Gly Gln Arg Gly Glu Ile Ile Asn Tyr Trp Arg Pro
5745 5750 5755
cac aag gac tac atg ctg cat gta gtc gag gca gtt ccc act acc 30192
His Lys Asp Tyr Met Leu His Val Val Glu Ala Val Pro Thr Thr
5760 5765 5770
tcc ccc act acc acc act acc act acc act acc acc tcc act acc 30237
Ser Pro Thr Thr Thr Thr Thr Thr Thr Thr Thr Thr Ser Thr Thr
5775 5780 5785
gct gcc cgc cat acc cgc aaa agc acc atg att agc aca aag ccc 30282
Ala Ala Arg His Thr Arg Lys Ser Thr Met Ile Ser Thr Lys Pro
5790 5795 5800
cct cct gct cac tcc cac gcc ggc ggg ccc atc ggt gcg acc tca 30327
Pro Pro Ala His Ser His Ala Gly Gly Pro Ile Gly Ala Thr Ser
5805 5810 5815
gaa acc acc gag ctt tgc ttc tgc caa tgc act aac gcc agc gct 30372
Glu Thr Thr Glu Leu Cys Phe Cys Gln Cys Thr Asn Ala Ser Ala
5820 5825 5830
cat gaa ctg ttc gac ctg gag aat gag gat gcc cag cag agc tcc 30417
His Glu Leu Phe Asp Leu Glu Asn Glu Asp Ala Gln Gln Ser Ser
5835 5840 5845
gct tgc ccg gcc ccg gcg gct gtg gag ccc gtt gcc ctg aag cag 30462
Ala Cys Pro Ala Pro Ala Ala Val Glu Pro Val Ala Leu Lys Gln
5850 5855 5860
atc ggt gat tct tcg ata att gac ttt tct gcc act ccc gaa tac 30507
Ile Gly Asp Ser Ser Ile Ile Asp Phe Ser Ala Thr Pro Glu Tyr
5865 5870 5875
cct ccc gat tct acc ttc cac atc acg ggt acc aaa gac cct aac 30552
Pro Pro Asp Ser Thr Phe His Ile Thr Gly Thr Lys Asp Pro Asn
5880 5885 5890
ctc tct ttc tac ctg atg ctg ctg ctc tgt atc tct gtg gtc tct 30597
Leu Ser Phe Tyr Leu Met Leu Leu Leu Cys Ile Ser Val Val Ser
5895 5900 5905
tcc gcg ctg atg tta ctg ggg atg ttc tgc tgc ctg atc tgc cgc 30642
Ser Ala Leu Met Leu Leu Gly Met Phe Cys Cys Leu Ile Cys Arg
5910 5915 5920
aga aag aga aaa gct cgc tct cag ggc caa cca ctg atg ccc ttc 30687
Arg Lys Arg Lys Ala Arg Ser Gln Gly Gln Pro Leu Met Pro Phe
5925 5930 5935
ccc tac ccc ccg gat ttt gca gat aac aag ata tgagctcgct 30730
Pro Tyr Pro Pro Asp Phe Ala Asp Asn Lys Ile
5940 5945
gctgacacta accgctttac tagcctgcgc tgctctaacc cttgtcgctt gcgaatccag 30790
attccacaat gtcacagttg tggcaggaga aaatgttaca ttcaactcca cggccgacgc 30850
ccggtggtcg tggagtggct ccggtagcta cctagatatc tgcaatagct ccacttcctc 30910
tagcataacc ccagccaagt accaatgcaa tgccaccctg ttcaccctca tcaacgcctc 30970
caccctggac aatggactct atgtaggcta cgtacccccc ggtgggcaag gaaagaccca 31030
cgcttacaac ctggaagtgc gccagcccag aaccactacc cagccttccc ccagcaccac 31090
caccaccacc agcagcagca gcaacagaag cagattcctg actttcattt tggccagctc 31150
atccgccgcc accgctcaga ccacccaggc catctacacc tctgtgcccg aaaccactca 31210
gacccaccgc ccagagacga ccaccgccac caccccacac acctccaccg accggatgcc 31270
ggccaacatc gcccccttgg ctcttcagaa tggacttaca agctccactc caaaaccagt 31330
ggatgcagcc gaagtctccg ccctcgtcaa tgactgggcg gggctgggaa tgtggtggtt 31390
cgccataggc atgatggcgc tctgcctgct tctgctctgg ctcatctgct gcctccaccg 31450
caggcgagcc agacccccca tctatagacc catcattgtc ctcaaccccg ataatgatgg 31510
gatccataga ttggatggcc tgaaaaacct acttttttct tttacagtat gataaattga 31570
gac atg cct cgc att ttc ttg tac ttg ctc ctt atc cca cct ttt 31615
Met Pro Arg Ile Phe Leu Tyr Leu Leu Leu Ile Pro Pro Phe
5950 5955 5960
ctg ggg tgt tct acg ctg gcc gct gtg tct cac ctg gag gta gac 31660
Leu Gly Cys Ser Thr Leu Ala Ala Val Ser His Leu Glu Val Asp
5965 5970 5975
tgt ctc cag ccc ttc gct gtc tac ctg ctt tac gga ctg gtc acc 31705
Cys Leu Gln Pro Phe Ala Val Tyr Leu Leu Tyr Gly Leu Val Thr
5980 5985 5990
ctc act ctc atc tgc agc cta atc aca gta atc atc gcc ttc atc 31750
Leu Thr Leu Ile Cys Ser Leu Ile Thr Val Ile Ile Ala Phe Ile
5995 6000 6005
cag tgc att gat tac atc tgt gtg cgc ctc gca tac ttc aga cac 31795
Gln Cys Ile Asp Tyr Ile Cys Val Arg Leu Ala Tyr Phe Arg His
6010 6015 6020
cac cca cag tac cga gac agg aac att gcc caa ctt cta aga ctt 31840
His Pro Gln Tyr Arg Asp Arg Asn Ile Ala Gln Leu Leu Arg Leu
6025 6030 6035
ctc taatc atg cat aag acc gtg atc tgc ctc ctg atc ctc tgc acc 31887
Leu Met His Lys Thr Val Ile Cys Leu Leu Ile Leu Cys Thr
6040 6045 6050
ctg ccc gcc ttc acc tcc tgc cag tac acc aca aaa gct ccg cgc 31932
Leu Pro Ala Phe Thr Ser Cys Gln Tyr Thr Thr Lys Ala Pro Arg
6055 6060 6065
aaa aga cat gcc tcc tgc cgc ttc acc caa ctg tgg aat atc ccc 31977
Lys Arg His Ala Ser Cys Arg Phe Thr Gln Leu Trp Asn Ile Pro
6070 6075 6080
aaa tgc tac aac gaa aag agc gag ctc tcc gaa gcc tgg ctg tat 32022
Lys Cys Tyr Asn Glu Lys Ser Glu Leu Ser Glu Ala Trp Leu Tyr
6085 6090 6095
ggg gtt atc tgt gtc tta gtt ttc tgc agc act gtc ttt gcc ctg 32067
Gly Val Ile Cys Val Leu Val Phe Cys Ser Thr Val Phe Ala Leu
6100 6105 6110
atg atc tac ccc cac att gat ttg gga tgg aac gcg atc gat gcc 32112
Met Ile Tyr Pro His Ile Asp Leu Gly Trp Asn Ala Ile Asp Ala
6115 6120 6125
atg agt tac ccc acc ttt ccc gcg ccc gag atg att cca ctg cga 32157
Met Ser Tyr Pro Thr Phe Pro Ala Pro Glu Met Ile Pro Leu Arg
6130 6135 6140
cag gtc gta ccc gtt gtc gtc aat caa cgc ccc cca tcc cct acg 32202
Gln Val Val Pro Val Val Val Asn Gln Arg Pro Pro Ser Pro Thr
6145 6150 6155
ccc act gag atc agc tac ttt aat cta aca ggc gga gat gac 32244
Pro Thr Glu Ile Ser Tyr Phe Asn Leu Thr Gly Gly Asp Asp
6160 6165 6170
tgacgcccta gatctagaaa tggacggcat cagtaccgag cagcgtctcc tagagaggcg 32304
caggcaggcg gttgagcaag agcgcctcaa tcaggagctc cgagatctcc ttaacctgca 32364
ccagtgcaaa agaggcatct tttgcctggc caagcaggcc aaagtcacct acgagaagac 32424
cggtaacagc caccgcctca gttacaaatt gcccacccag cgccagaagc tggtgctcat 32484
ggtgggtgag aatcccatca ccgtcaccca gcactcggta gaaaccgagg ggtgtctgca 32544
ctccccctgt cggggtccag aagacctctg caccctggtg aagaccctgt gcggtctcag 32604
agatttagtc ccctttaact aatcaaacac tggaatcaat aaaaaagaat cacttactta 32664
aaatcagtca gcaggtctct gtccagtttc ttcagcagca cctccttccc ctcctcccaa 32724
ctctggtact ccaaacgcct tctagcggca aacttcctcc acaccctgaa ggga atg 32781
Met
tca gat tct tgc tcc tgt ccc tcc gca ccc act atc ttc atg ttg 32826
Ser Asp Ser Cys Ser Cys Pro Ser Ala Pro Thr Ile Phe Met Leu
6175 6180 6185
ttg cag atg aag cgc acc aaa acg tct gac gag agc ttc aac ccc 32871
Leu Gln Met Lys Arg Thr Lys Thr Ser Asp Glu Ser Phe Asn Pro
6190 6195 6200
gtg tac ccc tat gac acg gaa aac ggt cct ccc tcc gtc cct ttc 32916
Val Tyr Pro Tyr Asp Thr Glu Asn Gly Pro Pro Ser Val Pro Phe
6205 6210 6215
ctc acc cct ccc ttc gtg tct ccc gat gga ttc caa gag agc ccc 32961
Leu Thr Pro Pro Phe Val Ser Pro Asp Gly Phe Gln Glu Ser Pro
6220 6225 6230
ccc ggg gtc ctg tct ctg aac ctg gcc gag ccc ctg gtc act tcc 33006
Pro Gly Val Leu Ser Leu Asn Leu Ala Glu Pro Leu Val Thr Ser
6235 6240 6245
cac ggc atg ctc gcc ctg aaa atg gga agt ggc ctc tcc ctg gac 33051
His Gly Met Leu Ala Leu Lys Met Gly Ser Gly Leu Ser Leu Asp
6250 6255 6260
gac gcc ggc aac ctc acc tct caa gat gtc acc acc act acc cct 33096
Asp Ala Gly Asn Leu Thr Ser Gln Asp Val Thr Thr Thr Thr Pro
6265 6270 6275
ccc ctg aaa aaa acc aag acc aac ctc agc cta gaa acc tca gcc 33141
Pro Leu Lys Lys Thr Lys Thr Asn Leu Ser Leu Glu Thr Ser Ala
6280 6285 6290
ccc ctg act gtg agc acc tca ggc gcc ctc acc cta gca gcc gcc 33186
Pro Leu Thr Val Ser Thr Ser Gly Ala Leu Thr Leu Ala Ala Ala
6295 6300 6305
gct ccc ctg gcg gtg gcc ggc acc tcc ctc acc atg caa tca gag 33231
Ala Pro Leu Ala Val Ala Gly Thr Ser Leu Thr Met Gln Ser Glu
6310 6315 6320
gcc ccc ctg aca gtc caa gat gca aaa ctc acc ctg gcc acc aag 33276
Ala Pro Leu Thr Val Gln Asp Ala Lys Leu Thr Leu Ala Thr Lys
6325 6330 6335
ggc ccc ctg acc gtg tct gaa ggc aaa ctg gcc ttg cag acc tcg 33321
Gly Pro Leu Thr Val Ser Glu Gly Lys Leu Ala Leu Gln Thr Ser
6340 6345 6350
gcc ccg ctg acg gcc gct gac agc agc acc ctc acc gtc agc gcc 33366
Ala Pro Leu Thr Ala Ala Asp Ser Ser Thr Leu Thr Val Ser Ala
6355 6360 6365
aca ccg ccc ctt agc aca agc aat ggc agc ttg ggt att gac atg 33411
Thr Pro Pro Leu Ser Thr Ser Asn Gly Ser Leu Gly Ile Asp Met
6370 6375 6380
caa gcc ccc att tac act act aac gga aaa ctg gga ctt aac ttt 33456
Gln Ala Pro Ile Tyr Thr Thr Asn Gly Lys Leu Gly Leu Asn Phe
6385 6390 6395
ggc gct ccc ctg cat gtg gta gac agc cta aat gca ctg act gta 33501
Gly Ala Pro Leu His Val Val Asp Ser Leu Asn Ala Leu Thr Val
6400 6405 6410
gtg act ggc caa ggt ctt acg ata aac ggt aca gcc cta caa act 33546
Val Thr Gly Gln Gly Leu Thr Ile Asn Gly Thr Ala Leu Gln Thr
6415 6420 6425
aga gtc tca ggt gcc ctc aac tat gac tca tca gga aac cta gaa 33591
Arg Val Ser Gly Ala Leu Asn Tyr Asp Ser Ser Gly Asn Leu Glu
6430 6435 6440
ttg aga gct gca ggg ggt atg cga gtt gat gca aat ggc aaa ctt 33636
Leu Arg Ala Ala Gly Gly Met Arg Val Asp Ala Asn Gly Lys Leu
6445 6450 6455
atc ctt gac gta gct tac cca ttt gat gct caa aac aac ctc agc 33681
Ile Leu Asp Val Ala Tyr Pro Phe Asp Ala Gln Asn Asn Leu Ser
6460 6465 6470
ctt aga ctt gga cag gga ccc ctg ttt gtt aac tct gcc cac aac 33726
Leu Arg Leu Gly Gln Gly Pro Leu Phe Val Asn Ser Ala His Asn
6475 6480 6485
ttg gat gtt aac tac aac aga ggc ctc tac ctg ttc aca tct gga 33771
Leu Asp Val Asn Tyr Asn Arg Gly Leu Tyr Leu Phe Thr Ser Gly
6490 6495 6500
aac acc aaa aag cta gaa gtt aat atc aaa aca gcc aaa ggc ctc 33816
Asn Thr Lys Lys Leu Glu Val Asn Ile Lys Thr Ala Lys Gly Leu
6505 6510 6515
att tat gat gac act gct ata gca atc aat cca ggc gat ggg cta 33861
Ile Tyr Asp Asp Thr Ala Ile Ala Ile Asn Pro Gly Asp Gly Leu
6520 6525 6530
gag ttt ggc tca ggc tca gat aca aat cca tta aaa act aaa ctt 33906
Glu Phe Gly Ser Gly Ser Asp Thr Asn Pro Leu Lys Thr Lys Leu
6535 6540 6545
gga ttg gga cta gag tat gac tcc agc aga gcc ata att gct aag 33951
Gly Leu Gly Leu Glu Tyr Asp Ser Ser Arg Ala Ile Ile Ala Lys
6550 6555 6560
ctg gga acc ggc cta agc ttt gac aac aca ggt gcc atc aca gtg 33996
Leu Gly Thr Gly Leu Ser Phe Asp Asn Thr Gly Ala Ile Thr Val
6565 6570 6575
ggc aac aac aat gat gac aag ctt acc ttg tgg acc aca cca gac 34041
Gly Asn Asn Asn Asp Asp Lys Leu Thr Leu Trp Thr Thr Pro Asp
6580 6585 6590
ccc tct ccc aac tgt aga att tat tca gaa aaa gat gct aaa ttt 34086
Pro Ser Pro Asn Cys Arg Ile Tyr Ser Glu Lys Asp Ala Lys Phe
6595 6600 6605
aca cta gtt tta act aaa tgc ggc agt cag gtg ttg gcc agc gtt 34131
Thr Leu Val Leu Thr Lys Cys Gly Ser Gln Val Leu Ala Ser Val
6610 6615 6620
tct gtt tta tct gta aaa ggc agc ctt gcg ccc atc agt ggc aca 34176
Ser Val Leu Ser Val Lys Gly Ser Leu Ala Pro Ile Ser Gly Thr
6625 6630 6635
gta act agc gct cag att att ctc aga ttt aat gaa aat gga gtt 34221
Val Thr Ser Ala Gln Ile Ile Leu Arg Phe Asn Glu Asn Gly Val
6640 6645 6650
cta cta agc aat tct tct ctt gac ccc caa tac tgg aac tac aga 34266
Leu Leu Ser Asn Ser Ser Leu Asp Pro Gln Tyr Trp Asn Tyr Arg
6655 6660 6665
aaa ggt gac ctt aca gag ggc act gca tat acc aac gca gtg gga 34311
Lys Gly Asp Leu Thr Glu Gly Thr Ala Tyr Thr Asn Ala Val Gly
6670 6675 6680
ttt atg ccc aac ctc aca gca tac cca aaa aca cag agt caa act 34356
Phe Met Pro Asn Leu Thr Ala Tyr Pro Lys Thr Gln Ser Gln Thr
6685 6690 6695
gct aaa agc aac att gta agc cag gtt tac ttg aat ggg gac aaa 34401
Ala Lys Ser Asn Ile Val Ser Gln Val Tyr Leu Asn Gly Asp Lys
6700 6705 6710
tcc aaa ccc atg atc ctc acc att acc ctc aat gga act aat gaa 34446
Ser Lys Pro Met Ile Leu Thr Ile Thr Leu Asn Gly Thr Asn Glu
6715 6720 6725
aca ggg gat gct aca gtt agc act tac tcc atg tca ttc tca tgg 34491
Thr Gly Asp Ala Thr Val Ser Thr Tyr Ser Met Ser Phe Ser Trp
6730 6735 6740
aat tgg aat gga agt aat tac att aat gaa acg ttc caa acc aac 34536
Asn Trp Asn Gly Ser Asn Tyr Ile Asn Glu Thr Phe Gln Thr Asn
6745 6750 6755
tct ttc acc ttc tcc tac atc gcc caa gaa taaaaaagca tgacgctgtt 34586
Ser Phe Thr Phe Ser Tyr Ile Ala Gln Glu
6760 6765
gtttgattca atgtgtttct gtttttattt ttcaagcaca acaaaatcat tttcaagtca 34646
tttttccatc ttagcttaat agacccagta gcttaataga cccagtagtg caaagcccca 34706
ttctagctta taaatcagac agtgataatc aaccaccacc accaccatac cttttgattc 34766
aggaaatcat catcatcaca ggatcctagt cgtcaggccg ccccctccct cccaagacac 34826
agaatacaca gtcctctccc cccgactggc tttaaacaac accatctggt tggtcacaga 34886
catgttctta ggggtgatat tccacacggt ctcctgccgc gccaggcgct cgtcggtgat 34946
gttgataaac tctcccggca gctcgctcaa gttcacgtcg ctgtccagcg gctgaacctc 35006
aggctgacgc gataactgcg cgaccggctg ctggacaaac ggaggccgcg cctacaaggg 35066
ggtagagtca taatcctcgg tcaggatagg acggtgatgc agcagcagcg agcgaatcat 35126
atgctgccgc cgccgctccg tccggcagga aaacaacaca ccggtggtct cctccgcgat 35186
aatccgcacc gcccgcagca tcagcttcct cgttctccgc gcgcagcacc gcaccctgat 35246
ctcgctcagg ccggcgcagt aggtacaaca cagcaccacg atgttattca tgatcccaca 35306
gtgcagggcg ctgtatccaa agctcatgcc gggaaccacc gcccccacgt ggccgtcgta 35366
ccacaagcgc acgtaaatca agtgtcgacc cctcatgaac gtgctggcca tatacatcac 35426
ttccttgggc atgttgtaat tcaccacctc ccgataccag ataaacctct ggttgaacat 35486
ggcgccttcc accaccatcc tgaaccaaga ggccagaacc tgcccaccgg ctatgcactg 35546
cagggaaccc gggttggaac aatgacaatg cagactccag ggctcgtaac cgtggatcat 35606
ccggctgccg aaggcatcga tgttggcaca acacagacac acgtgcatgc actttctcat 35666
gattagcagc tcctccctcg tcaagatcat atcccaagga attacccatt cttgaatcaa 35726
cgtaaagccc acacagcagg gaaggcctcg cacataactc acattgtgca tggtcagcgt 35786
gttgcattcc ggaaacagcg gatgatcctc cagtatcgag gcgcgggtct cgttctcaca 35846
gggaggtaaa ggggccctgc tgtacggact gtgccgggac gaccgagatc gtgttgaacg 35906
tagtgtcatg gaaaagggaa cgccggacgt ggtcatactt cttgaaacag aaccaggttc 35966
gcgcgtggca ggcttccttg cgtctgcggt ctcgccgtct agctcgctcc gtgtgatagt 36026
tgtagtacag ccactcccgc agaccgtcga ggcgccccct ggcttccgga tctatgtaga 36086
ctccgtcttg cgccgcggcc ctgataatat ccaccaccgt agaataagca acacccagcc 36146
aagcaataca ctcgctctgc gagcggcaga caggaggagc gggtagagat gggaggacca 36206
tgataaaaaa ctttttaaag aaaattctcc acttcttcga aaacaagatc tatcaagtgg 36266
cagcgctccc ctccactggc gcggtcaaac tctacggcca aagcacagat aacggcattt 36326
ctaagatgtt ccttaacggc atccaaaaga cacaccgctc tcaagttgca ataaactatt 36386
aatgaaaacc catccggctg attgtccaat atagacccgc cggcggcgtc caccaaaccc 36446
agataatttt cgtctctcca gcgatttaaa atctgtctaa gcaaatccct tatgtcaagt 36506
ccgaccatct gaaaaatctg ctcaagagcg ccctccacct tcatcatcaa gcagcgcatc 36566
atgattgcaa aaattcaggt tcttcagaga cctgtataag attcaaaacg ggaacattaa 36626
ccaaaattcc tctgtcgcgc agatcccttc gcagggcaag ctgaacataa tcagacaggt 36686
ctgaacggac cagtgaggcc aaatccccac caggaaccag atccagagac cctatactga 36746
ttatgacgcg catactcggg gctatgctga ccagcgtagc gccgaggtag gcgtgctgca 36806
tgggcggcga gagaaaatgc aaagtgctgg ttaaaaaatc aggcaaagcc tcgcgcaaaa 36866
aagctaacac atcgtaatca tgctcatgca ggtagttgca ggtaagctca ggaaccaaaa 36926
cggaataaca cacgattttc ctctcaaaca tgacttcgcg gatactgcgt taaaaaacaa 36986
aaattataaa taaaaattaa ttaaatatct taaatatcag aagcctgtct tacaacagga 37046
aaaaccactc tgattaacat aagacgagcc acgggcatgc cggcataacc gtaaaaaaat 37106
tggtccccgt gatttacaag taccacagac agctccccgg tcatgtcggg ggtcatcatg 37166
tgagactgtg tatacacgtc tgggttgtta acatcagaca gagaaagaaa tcggcctatg 37226
tagcccggag gtataatcac ccgcaggcgg aggtaaagca aaataacccc cataggagga 37286
atcacaaaat tagtaggaga aaaaaataca taaacaccag agaaaccctc ttgctgaggc 37346
aaaatagcgc cctcccggac caaaacaaca taaagcgctt ccacaggagc agccataaca 37406
aagacccgag ccttaccagt aaaataaaaa agatatctca acgcagcacc agcaccaaca 37466
cctgtcagtg tgtcaggcca agtgccgagc gagtatatat aggaataaaa agtgacgtaa 37526
acggttaaag tccagaaaac gcccagaaaa accgcacgcg aacctacgcc ccgaaacgaa 37586
agccaaaaaa cagtagacac tcccttccgg cgtcaacttc cgctttccca cgctacgtca 37646
cttccccggt caaacaaact acatttccca aacatacaag ttaccacgcc ccaaacaccg 37706
cccacacctc cccgcccgcc ggcccgcccc gcgccccgcc tcccgccccg cgtcacatcc 37766
cgctccgccc acctcattat catattggct tcaatccaaa ataaggtata ttattgatga 37826
tg 37828
<210> 33
<211> 507
<212> PRT
<213> Simian adenovirus 31
<400> 33
Met Glu Arg Arg Asp Pro Leu Glu Phe Gly Leu Arg Pro Gly Phe Ser
1 5 10 15
Gly His Ala Thr Val Glu Gly Met Asp Gln Ala Gln Glu Gln Ala Ala
20 25 30
Thr Val Val Tyr Arg Pro Pro Ala Ala Asp Ser Gly Gly Gly Ala Thr
35 40 45
Gly Arg Val Arg Gly Pro Gly Pro Ser Gly Ser Gly Ala Gly Gly Ala
50 55 60
Glu Ala Gly Arg Glu Glu Arg Val Glu Pro Gly Asn Arg Ala Glu Arg
65 70 75 80
Pro Ser Thr Ser Gly Val Asn Val Gly Gln Val Ala Asp Leu Phe Pro
85 90 95
Glu Leu Arg Arg Ile Leu Thr Ile Arg Glu Asp Gly Gln Phe Val Lys
100 105 110
Gly Leu Lys Arg Glu Arg Gly Ala Ser Glu His Asn Glu Glu Ala Ser
115 120 125
Asn Leu Ala Phe Ser Leu Met Thr Arg His Arg Pro Glu Cys Ile Thr
130 135 140
Phe Gln Gln Ile Lys Asp Asn Cys Ala Asn Glu Leu Asp Leu Leu Gly
145 150 155 160
Gln Lys Tyr Ser Ile Glu Gln Leu Thr Thr Tyr Trp Leu Gln Pro Gly
165 170 175
Asp Asp Leu Glu Glu Ala Ile Arg Val Tyr Ala Lys Val Ala Leu Arg
180 185 190
Pro Asp Cys Lys Tyr Lys Leu Lys Gly Leu Val Asn Ile Arg Asn Cys
195 200 205
Cys Tyr Ile Ser Gly Asn Gly Ala Glu Val Glu Ile Glu Thr Glu Asp
210 215 220
Arg Val Ala Phe Arg Cys Cys Met Val Asn Met Trp Pro Gly Val Leu
225 230 235 240
Gly Met Asp Gly Val Val Ile Met Asn Val Arg Phe Thr Gly Pro Asn
245 250 255
Phe Asn Gly Thr Val Phe Leu Gly Asn Thr Asn Leu Val Leu His Gly
260 265 270
Val Ser Phe Tyr Gly Phe Asn Asn Thr Cys Val Glu Ala Trp Thr Asp
275 280 285
Val Lys Val Arg Gly Cys Ala Phe Tyr Gly Cys Trp Lys Ala Ile Val
290 295 300
Ser Arg Pro Lys Ser Arg Ser Ser Ile Lys Lys Cys Leu Phe Glu Arg
305 310 315 320
Cys Thr Leu Gly Ile Leu Ala Glu Gly Asn Cys Arg Val Arg His Asn
325 330 335
Val Ala Ser Glu Cys Gly Cys Phe Met Leu Val Lys Ser Val Ala Ile
340 345 350
Ile Lys His Asn Met Val Cys Gly Asn Ser Glu Asp Lys Ala Ser Gln
355 360 365
Met Leu Thr Cys Ala Asp Gly Asn Cys His Leu Leu Lys Thr Ile His
370 375 380
Ile Thr Ser His Gly Arg Lys Ala Trp Pro Val Phe Glu His Asn Val
385 390 395 400
Leu Thr Arg Cys Ser Leu His Leu Gly Asn Arg Arg Gly Val Phe Leu
405 410 415
Pro Tyr Gln Cys Asn Leu Ser His Thr Lys Ile Leu Leu Glu Pro Glu
420 425 430
Ser Met Ser Lys Val Asn Leu Asn Gly Val Phe Asp Met Thr Met Lys
435 440 445
Ile Trp Lys Val Leu Arg Tyr Asp Glu Thr Arg Ser Arg Cys Arg Pro
450 455 460
Cys Glu Cys Gly Gly Lys His Met Arg Asn Gln Pro Val Met Leu Asp
465 470 475 480
Val Thr Glu Glu Leu Arg Thr Asp His Leu Val Leu Ala Cys Thr Arg
485 490 495
Ala Glu Phe Gly Ser Ser Asp Glu Asp Thr Asp
500 505
<210> 34
<211> 154
<212> PRT
<213> Simian adenovirus 31
<400> 34
Met Ser Gly Ser Ser Ser Ser Ser Ser Ser Ser Ser Ala Leu Asp Gly
1 5 10 15
Ser Ile Val Ser Pro Tyr Leu Thr Thr Arg Met Pro His Trp Ala Gly
20 25 30
Val Arg Gln Asn Val Met Gly Ser Ser Ile Asp Gly Arg Pro Val Leu
35 40 45
Pro Ala Asn Ser Ala Thr Leu Thr Tyr Ala Thr Val Ala Gly Thr Pro
50 55 60
Leu Asp Ala Thr Ala Ala Ala Ala Ala Thr Ala Ala Ala Ser Ala Val
65 70 75 80
Arg Ser Leu Ala Thr Asp Phe Ala Phe Leu Gly Pro Leu Ala Thr Gly
85 90 95
Ala Thr Ser Arg Ala Ala Ala Ala Ala Val Arg Asp Asp Lys Leu Thr
100 105 110
Ala Leu Leu Ala Gln Leu Asp Ala Leu Thr Arg Glu Leu Gly Asp Leu
115 120 125
Ser Gln Gln Val Met Ala Leu Arg Gln Gln Val Ser Ser Leu Gln Ala
130 135 140
Gly Gly Asn Ala Ser Pro Thr Asn Ala Val
145 150
<210> 35
<211> 420
<212> PRT
<213> Simian adenovirus 31
<400> 35
Met His Pro Val Leu Arg Gln Met Arg Pro Pro Pro Gln Gln Gln His
1 5 10 15
Gln Gln Gln Glu Arg Gln Pro Gln Gln Gln Gln Arg Glu Ser Cys Arg
20 25 30
Ala Pro Ser Pro Thr Leu Gly Gly Pro Ala Thr Ser Ala Ser Ala Ala
35 40 45
Val Ser Gly Ala Gly Gly Gly Gly Gly Gly Leu Ala Asp Asp Pro Glu
50 55 60
Glu Pro Pro Arg Arg Arg Ala Arg His Tyr Leu Asp Leu Glu Glu Gly
65 70 75 80
Glu Gly Leu Ala Arg Leu Gly Ala Pro Ser Pro Glu Arg His Pro Arg
85 90 95
Val Gln Leu Lys Arg Asp Ser Arg Glu Ala Tyr Val Pro Arg Gln Asn
100 105 110
Leu Phe Arg Asp Arg Ala Gly Glu Glu Pro Glu Glu Met Arg Asp Arg
115 120 125
Arg Phe Ser Ala Gly Arg Glu Leu Arg Gln Gly Leu Asn Arg Glu Arg
130 135 140
Leu Leu Arg Glu Glu Asp Phe Glu Pro Asp Ala Arg Thr Gly Ile Ser
145 150 155 160
Pro Ala Arg Ala His Val Ala Ala Ala Asp Leu Val Thr Ala Tyr Glu
165 170 175
Gln Thr Val Asn Gln Glu Ile Asn Phe Gln Lys Ser Phe Asn Asn His
180 185 190
Val Arg Thr Leu Val Ala Arg Glu Glu Val Thr Ile Gly Leu Met His
195 200 205
Leu Trp Asp Phe Val Ser Ala Leu Val Gln Asn Pro Asn Ser Lys Pro
210 215 220
Leu Thr Ala Gln Leu Phe Leu Ile Val Gln His Ser Arg Asp Asn Glu
225 230 235 240
Ala Phe Arg Asp Ala Leu Leu Asn Ile Thr Glu Pro Glu Gly Arg Trp
245 250 255
Leu Leu Asp Leu Ile Asn Ile Leu Gln Ser Ile Val Val Gln Glu Arg
260 265 270
Ser Leu Ser Leu Ala Asp Lys Val Ala Ala Ile Asn Tyr Ser Met Leu
275 280 285
Ser Leu Gly Lys Phe Tyr Ala Arg Lys Ile Tyr Gln Thr Pro Tyr Val
290 295 300
Pro Ile Asp Lys Glu Val Lys Ile Asp Gly Phe Tyr Met Arg Met Ala
305 310 315 320
Leu Lys Val Leu Thr Leu Ser Asp Asp Leu Gly Val Tyr Arg Asn Glu
325 330 335
Arg Ile His Lys Ala Val Ser Val Ser Arg Arg Arg Glu Leu Ser Asp
340 345 350
Arg Glu Leu Met His Ser Leu Gln Arg Ala Leu Ala Gly Ala Gly Ser
355 360 365
Gly Asp Arg Glu Ala Glu Ser Tyr Phe Asp Ala Gly Ala Asp Leu Arg
370 375 380
Trp Ala Pro Ser Arg Arg Ala Leu Glu Ala Ala Gly Val Arg Glu Asp
385 390 395 400
Tyr Asp Glu Asp Gly Glu Glu Asp Glu Glu Tyr Glu Leu Glu Glu Gly
405 410 415
Glu Tyr Leu Asp
420
<210> 36
<211> 588
<212> PRT
<213> Simian adenovirus 31
<400> 36
Met Gln Asp Pro Asn Val Val Asp Pro Ala Leu Arg Ala Ala Leu Gln
1 5 10 15
Ser Gln Pro Ser Gly Leu Asn Ser Ser Asp Asp Trp Arg Gln Val Met
20 25 30
Asp Arg Ile Met Ser Leu Thr Ala Arg Asn Pro Asp Ala Phe Arg Gln
35 40 45
Gln Pro Gln Ala Asn Arg Leu Ser Ala Ile Leu Glu Ala Val Val Pro
50 55 60
Ala Arg Ser Asn Pro Thr His Glu Lys Val Leu Ala Ile Val Asn Ala
65 70 75 80
Leu Ala Glu Asn Arg Ala Ile Arg Pro Asp Glu Ala Gly Leu Val Tyr
85 90 95
Asp Ala Leu Leu Gln Arg Val Ala Arg Tyr Asn Ser Gly Asn Val Gln
100 105 110
Thr Asn Leu Asp Arg Leu Val Gly Asp Val Arg Glu Ala Val Ala Gln
115 120 125
Arg Glu Arg Ala Asp Arg Gln Gly Asn Leu Gly Ser Met Val Ala Leu
130 135 140
Asn Ala Phe Leu Ser Thr Gln Pro Ala Asn Val Pro Arg Gly Gln Glu
145 150 155 160
Asp Tyr Thr Asn Phe Val Ser Ala Leu Arg Leu Met Val Thr Glu Thr
165 170 175
Pro Gln Ser Glu Val Tyr Gln Ser Gly Pro Asp Tyr Phe Phe Gln Thr
180 185 190
Ser Arg Gln Gly Leu Gln Thr Val Asn Leu Ser Gln Ala Phe Lys Asn
195 200 205
Leu Arg Gly Leu Trp Gly Val Lys Ala Pro Thr Gly Asp Arg Ala Thr
210 215 220
Val Ser Ser Leu Leu Thr Pro Asn Ser Arg Leu Leu Leu Leu Leu Ile
225 230 235 240
Ala Pro Phe Thr Asp Ser Gly Ser Val Ser Arg Asp Thr Tyr Leu Gly
245 250 255
His Leu Leu Thr Leu Tyr Arg Glu Ala Ile Gly Gln Ala Gln Val Asp
260 265 270
Glu His Thr Phe Gln Glu Ile Thr Ser Val Ser Arg Ala Leu Gly Gln
275 280 285
Glu Asp Thr Ser Ser Leu Glu Ala Thr Leu Asn Tyr Leu Leu Thr Asn
290 295 300
Arg Arg Gln Lys Ile Pro Ser Leu His Ser Leu Thr Ser Glu Glu Glu
305 310 315 320
Arg Ile Leu Arg Tyr Val Gln Gln Ser Val Ser Leu Asn Leu Met Arg
325 330 335
Asp Gly Val Thr Pro Ser Val Ala Leu Asp Met Thr Ala Arg Asn Met
340 345 350
Glu Pro Gly Met Tyr Ala Ala His Arg Pro Tyr Ile Asn Arg Leu Met
355 360 365
Asp Tyr Leu His Arg Ala Ala Ala Val Asn Pro Glu Tyr Phe Thr Asn
370 375 380
Ala Ile Leu Asn Pro His Trp Leu Pro Pro Pro Gly Phe Tyr Ser Gly
385 390 395 400
Gly Phe Glu Val Pro Glu Ala Asn Asp Gly Phe Leu Trp Asp Asp Met
405 410 415
Asp Asp Ser Val Phe Ser Pro Arg Pro Gln Ala Leu Ala Glu Ala Ser
420 425 430
Leu Leu Arg Pro Lys Lys Glu Glu Ser Arg His Gly Pro Arg Gly Ser
435 440 445
Ser Ala Ser Leu Ser Glu Leu Gly Ala Ala Ala Ala Arg Pro Gly Ser
450 455 460
Leu Gly Gly Ser Pro Phe Pro Ser Leu Val Gly Ser Leu Gln Ser Gly
465 470 475 480
Arg Thr Thr Arg Pro Arg Leu Leu Gly Glu Asp Glu Tyr Leu Asn Asn
485 490 495
Ser Leu Met Gln Pro Val Arg Glu Lys Asn Leu Pro Pro Ala Phe Pro
500 505 510
Asn Asn Gly Ile Glu Ser Leu Val Asp Lys Met Ser Arg Trp Lys Thr
515 520 525
Tyr Ala Gln Glu His Arg Asp Ala Pro Ala Leu Arg Pro Pro Thr Arg
530 535 540
Arg Gln Arg His Asp Arg Gln Arg Gly Leu Val Trp Asp Asp Glu Asp
545 550 555 560
Ser Ala Asp Asp Ser Ser Val Leu Asp Leu Gly Gly Ser Gly Asn Pro
565 570 575
Phe Ala His Leu Arg Pro Arg Leu Gly Arg Met Phe
580 585
<210> 37
<211> 589
<212> PRT
<213> Simian adenovirus 31
<400> 37
Met Arg Arg Ala Ala Met Tyr Gln Glu Gly Pro Pro Pro Ser Tyr Glu
1 5 10 15
Ser Val Val Gly Ala Ala Ser Pro Phe Ala Ser Gln Leu Glu Pro Pro
20 25 30
Tyr Val Pro Pro Arg Tyr Leu Arg Pro Thr Gly Gly Arg Asn Ser Ile
35 40 45
Arg Tyr Ser Glu Leu Ala Pro Leu Phe Asp Thr Thr Arg Val Tyr Leu
50 55 60
Val Asp Asn Lys Ser Ala Asp Val Ala Ser Leu Asn Tyr Gln Asn Asp
65 70 75 80
His Ser Asn Phe Leu Thr Thr Val Ile Gln Asn Asn Asp Tyr Ser Pro
85 90 95
Ser Glu Ala Ser Thr Gln Thr Ile Asn Leu Asp Asp Arg Ser His Trp
100 105 110
Gly Gly Asp Leu Lys Thr Ile Leu His Thr Asn Met Pro Asn Val Asn
115 120 125
Glu Phe Met Phe Thr Asn Lys Phe Lys Ala Arg Val Met Val Ser Arg
130 135 140
Ser His Thr Lys Asp Asp Arg Val Glu Leu Lys Tyr Glu Trp Val Glu
145 150 155 160
Phe Glu Leu Pro Glu Gly Asn Tyr Ser Glu Thr Met Thr Ile Asp Leu
165 170 175
Met Asn Asn Ala Ile Val Glu His Tyr Leu Lys Val Gly Arg Gln Asn
180 185 190
Gly Val Leu Glu Ser Asp Ile Gly Val Lys Phe Asp Thr Arg Asn Phe
195 200 205
Arg Leu Gly Leu Asp Pro Val Thr Gly Leu Val Met Pro Gly Val Tyr
210 215 220
Thr Asn Glu Ala Phe His Pro Asp Ile Val Leu Leu Pro Gly Cys Gly
225 230 235 240
Val Asp Phe Thr Tyr Ser Arg Leu Ser Asn Leu Leu Gly Ile Arg Lys
245 250 255
Arg Gln Pro Phe Gln Glu Gly Phe Arg Ile Thr Tyr Glu Asp Leu Glu
260 265 270
Gly Gly Asn Ile Pro Ala Leu Leu Asp Val Glu Ala Tyr Gln Asp Ser
275 280 285
Leu Lys Glu Asn Glu Ala Gly Gln Glu Asp Thr Ala Ser Ala Ala Ala
290 295 300
Ala Ala Ala Ala Ala Thr Pro Ala Glu Gln Gly Glu Asp Ala Ala Ala
305 310 315 320
Ala Ala Gly Ala Ala Glu Ala Glu Ala Glu Pro Ala Met Val Val Glu
325 330 335
Glu Gln Glu Glu Asp Met Asn Asp Ser Ala Val Arg Gly Asp Thr Phe
340 345 350
Val Thr Arg Gly Glu Glu Lys Gln Ala Glu Ala Glu Ala Ala Ala Glu
355 360 365
Glu Lys Gln Ala Ala Glu Ala Ala Ala Ala Leu Ala Ala Ala Glu Ala
370 375 380
Ala Glu Ala Glu Ser Glu Gly Ala Lys Lys Glu Pro Val Ile Lys Pro
385 390 395 400
Leu Thr Glu Asp Ser Lys Lys Arg Ser Tyr Asn Val Leu Lys Asp Ser
405 410 415
Thr Asn Thr Ala Tyr Arg Ser Trp Tyr Leu Ala Tyr Asn Tyr Gly Asp
420 425 430
Pro Ser Thr Gly Val Arg Ser Trp Thr Leu Leu Cys Thr Pro Asp Val
435 440 445
Thr Cys Gly Ser Glu Gln Val Tyr Trp Ser Leu Pro Asp Met Met Gln
450 455 460
Asp Pro Val Thr Phe Arg Ser Thr Arg Gln Val Ser Asn Phe Pro Val
465 470 475 480
Val Gly Ala Glu Leu Leu Pro Val His Ser Lys Ser Phe Tyr Asn Asp
485 490 495
Gln Ala Val Tyr Ser Gln Leu Ile Arg Gln Phe Thr Ser Leu Thr His
500 505 510
Val Phe Asn Arg Phe Pro Glu Asn Gln Ile Leu Ala Arg Pro Pro Ala
515 520 525
Pro Thr Ile Thr Thr Val Ser Glu Asn Val Pro Ala Leu Thr Asp His
530 535 540
Gly Thr Leu Pro Leu Arg Asn Ser Ile Gly Gly Val Gln Arg Val Thr
545 550 555 560
Val Thr Asp Ala Arg Arg Arg Thr Cys Pro Tyr Val Tyr Lys Ala Leu
565 570 575
Gly Ile Val Ser Pro Arg Val Leu Ser Ser Arg Thr Phe
580 585
<210> 38
<211> 198
<212> PRT
<213> Simian adenovirus 31
<400> 38
Met Ser Ile Leu Ile Ser Pro Ser Asn Asn Ser Gly Trp Gly Leu Leu
1 5 10 15
Arg Ala Pro Ser Lys Met Phe Gly Gly Ala Arg Lys Arg Ser Glu Gln
20 25 30
His Pro Val Arg Val Arg Gly His Phe Arg Ala Pro Trp Gly Ala His
35 40 45
Lys Arg Gly Arg Thr Gly Arg Thr Thr Val Asp Asp Ala Ile Asp Ser
50 55 60
Val Val Glu Gln Ala Arg Asn Tyr Arg Pro Ala Val Ser Thr Val Asp
65 70 75 80
Ala Ala Ile Gln Thr Val Val Gln Gly Ala Arg Arg Tyr Ala Lys Leu
85 90 95
Lys Ser Arg Arg Lys Arg Val Ala Arg Arg His Arg Arg Arg Pro Gly
100 105 110
Ala Ala Ala Lys Arg Ala Ala Ala Ala Leu Leu Arg Arg Ala Lys Arg
115 120 125
Thr Gly Arg Arg Ala Ala Met Arg Ala Ala Arg Arg Leu Ala Ala Gly
130 135 140
Ile Thr Ala Thr Ala Met Ala Pro Arg Thr Arg Arg Arg Ala Ala Ala
145 150 155 160
Ala Ala Ala Ala Ala Ile Ser Asp Met Ala Thr Arg Arg Arg Gly Asn
165 170 175
Val Tyr Trp Val Arg Asp Ser Val Ser Gly Val Arg Val Pro Val Arg
180 185 190
Phe Arg Pro Pro Arg Thr
195
<210> 39
<211> 373
<212> PRT
<213> Simian adenovirus 31
<400> 39
Met Ser Lys Arg Lys Ile Lys Glu Glu Met Leu Gln Val Ile Ala Pro
1 5 10 15
Glu Ile Tyr Gly Pro Pro Lys Lys Glu Glu Gln Asp Phe Lys Ser Arg
20 25 30
Lys Ile Lys Arg Val Lys Lys Lys Lys Lys Asp Asp Asp Ala Asp Gly
35 40 45
Glu Val Glu Phe Leu Arg Ala Thr Ala Pro Arg Arg Pro Val Gln Trp
50 55 60
Lys Gly Arg Arg Val Lys Arg Val Leu Arg Pro Gly Thr Ala Val Val
65 70 75 80
Phe Thr Pro Gly Glu Arg Ser Thr Arg Thr Phe Lys Arg Val Tyr Asp
85 90 95
Glu Val Tyr Gly Asp Glu Asp Leu Leu Glu Gln Ala Asn Glu Arg Phe
100 105 110
Gly Glu Phe Ala Tyr Gly Lys Arg Gln Arg Pro Leu Gly Lys Glu Asp
115 120 125
Glu Asp Leu Leu Ala Leu Pro Leu Asp Arg Gly Asn Pro Thr Pro Ser
130 135 140
Leu Lys Pro Val Thr Leu Gln Gln Val Leu Pro Ser Ser Ala Pro Ser
145 150 155 160
Glu Thr Lys Arg Gly Leu Lys Arg Glu Gly Gly Asp Leu Ala Pro Thr
165 170 175
Val Gln Leu Met Val Pro Lys Arg Gln Arg Leu Glu Asp Val Leu Glu
180 185 190
Lys Met Lys Val Asp Pro Gly Leu Gln Pro Asp Ile Arg Val Arg Pro
195 200 205
Ile Lys Gln Val Ala Pro Gly Leu Gly Val Gln Thr Val Asp Val Val
210 215 220
Ile Pro Thr Gly Asn Ser Pro Ala Ala Ala Thr Thr Thr Thr Ala Thr
225 230 235 240
Ser Thr Asp Met Glu Thr Gln Thr Val Pro Ala Ala Ala Ala Ala Ala
245 250 255
Ala Ala Thr Ala Ala Thr Ser Ser Ala Glu Val Gln Thr Asp Pro Trp
260 265 270
Leu Pro Pro Ala Met Ala Pro Arg Ala Arg Arg Gly Arg Arg Lys Tyr
275 280 285
Gly Ala Ala Asn Ala Leu Leu Pro Glu Tyr Ala Leu His Pro Ser Ile
290 295 300
Ala Pro Thr Pro Gly Tyr Arg Gly Tyr Thr Tyr Arg Pro Arg Arg Ala
305 310 315 320
Lys Gly Ser Thr Arg Arg Pro Arg Arg Arg Ala Ala Thr Thr Arg Arg
325 330 335
Arg Arg Arg Ser Arg Arg Gln Pro Ala Leu Ala Pro Ile Ser Val Arg
340 345 350
Arg Val Ala Arg Asp Gly Arg Thr Leu Val Leu Pro Arg Ala Arg Tyr
355 360 365
His Pro Ser Ile Val
370
<210> 40
<211> 81
<212> PRT
<213> Simian adenovirus 31
<400> 40
Met Ala Leu Thr Cys Arg Leu Arg Phe Pro Val Pro Gly Tyr Arg Gly
1 5 10 15
Gly Arg Ser Arg Arg Arg Arg Gly Leu Ala Gly Arg Gly Leu Ser Gly
20 25 30
Gly Ser Arg Arg Ala His Arg Arg Arg Arg Ala Thr Ser Arg Arg Met
35 40 45
Arg Gly Gly Val Leu Pro Leu Leu Ile Pro Leu Ile Ala Ala Ala Ile
50 55 60
Gly Ala Val Pro Gly Ile Ala Ser Val Ala Leu Gln Ala Ser Gln Arg
65 70 75 80
Arg
<210> 41
<211> 253
<212> PRT
<213> Simian adenovirus 31
<400> 41
Met Glu Asp Ile Asn Phe Ala Ser Leu Ala Pro Arg His Gly Ser Arg
1 5 10 15
Pro Phe Leu Gly His Trp Asn Asp Ile Gly Thr Ser Asn Met Ser Gly
20 25 30
Gly Ala Phe Ser Trp Gly Ser Leu Trp Ser Gly Ile Lys Ser Ile Gly
35 40 45
Ser Ala Val Lys Asn Tyr Gly Thr Arg Ala Trp Asn Ser Ser Thr Gly
50 55 60
Gln Met Leu Arg Asp Lys Leu Lys Glu Gln Asn Phe Gln Gln Lys Val
65 70 75 80
Val Glu Gly Leu Ala Ser Gly Ile Asn Gly Val Val Asp Leu Ala Asn
85 90 95
Gln Ala Val Gln Asn Lys Ile Asn Ser Arg Leu Asp Pro Arg Pro Pro
100 105 110
Val Glu Glu Val Pro Pro Ala Leu Glu Thr Val Ser Pro Asp Gly Arg
115 120 125
Gly Glu Lys Arg Pro Arg Pro Asp Arg Glu Glu Thr Thr Leu Val Thr
130 135 140
Gln Thr Asp Glu Pro Pro Pro Tyr Glu Glu Ala Leu Lys Gln Gly Leu
145 150 155 160
Pro Thr Thr Arg Pro Ile Ala Pro Met Ala Thr Gly Val Val Gly Arg
165 170 175
His Thr Pro Ala Thr Leu Asp Leu Pro Pro Pro Ala Asp Val Pro Gln
180 185 190
Gln Gln Lys Ala Ala Gln Pro Gly Pro Pro Ala Thr Ala Pro Arg Ser
195 200 205
Ser Ala Gly Pro Leu Arg Arg Ala Ala Ser Gly Pro Arg Gly Gly Val
210 215 220
Ser Arg His Ser Ser Gly Asn Trp Gln Ser Thr Leu Asn Ser Ile Val
225 230 235 240
Gly Leu Gly Val Arg Ser Val Lys Arg Arg Arg Cys Tyr
245 250
<210> 42
<211> 954
<212> PRT
<213> Simian adenovirus 31
<400> 42
Met Ala Thr Pro Ser Met Met Pro Gln Trp Ser Tyr Met His Ile Ser
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Glu Ser Tyr Phe Ser Leu Ser Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Thr Leu Arg Phe Ile Pro Val Asp Arg Glu Asp Thr Ala Tyr Ser Tyr
65 70 75 80
Lys Ala Arg Phe Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Thr
100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125
Ala Pro Asn Pro Cys Glu Trp Asp Glu Ala Ala Thr Ala Leu Asp Ile
130 135 140
Asp Leu Asn Ala Glu Glu Asp Glu Glu Gly Asp Glu Ala Gln Gly Glu
145 150 155 160
Ala Asp Gln Gln Lys Thr His Val Phe Gly Gln Ala Pro Tyr Ser Gly
165 170 175
Gln Asn Ile Thr Lys Glu Gly Ile Gln Ile Gly Ile Asp Ala Thr Ser
180 185 190
Gln Ala Gln Thr Pro Leu Tyr Ala Asp Lys Thr Phe Gln Pro Glu Pro
195 200 205
Gln Ile Gly Glu Ser Gln Trp Asn Glu Thr Glu Ile Ser Tyr Gly Ala
210 215 220
Gly Arg Val Leu Lys Lys Thr Thr Leu Met Lys Pro Cys Tyr Gly Ser
225 230 235 240
Tyr Ala Arg Pro Thr Asn Glu Asn Gly Gly Gln Gly Ile Leu Leu Glu
245 250 255
Gln Asp Gly Lys Lys Glu Ser Gln Val Glu Met Gln Phe Phe Ser Thr
260 265 270
Thr Gln Ala Ala Ala Gly Asn Ser Asp Asn Pro Thr Pro Lys Leu Val
275 280 285
Leu Tyr Ser Glu Asp Val Asn Leu Glu Thr Pro Asp Thr His Ile Ser
290 295 300
Tyr Met Pro Thr Asn Asn Glu Thr Asn Ser Arg Glu Leu Leu Gly Gln
305 310 315 320
Gln Ala Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp Asn Phe
325 330 335
Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val Leu Ala
340 345 350
Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp Arg Asn
355 360 365
Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Met Gly Asp Arg Thr
370 375 380
Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp Pro Asp
385 390 395 400
Val Arg Ile Ile Glu Asn His Gly Thr Glu Asp Glu Leu Pro Asn Tyr
405 410 415
Cys Phe Pro Leu Gly Gly Ile Ile Asn Thr Glu Thr Phe Thr Lys Val
420 425 430
Lys Pro Lys Ala Gly Gln Asp Ala Gln Trp Glu Lys Asp Ser Glu Phe
435 440 445
Ser Asp Lys Asn Glu Ile Arg Val Gly Asn Asn Phe Ala Met Glu Ile
450 455 460
Asn Ile Asn Ala Asn Leu Trp Arg Asn Phe Leu Tyr Ser Asn Val Ala
465 470 475 480
Leu Tyr Leu Pro Asp Lys Leu Lys Tyr Thr Pro Ser Asn Val Gln Ile
485 490 495
Ser Asn Asn Pro Asn Ser Tyr Asp Tyr Met Asn Lys Arg Val Val Ala
500 505 510
Pro Gly Leu Val Asp Cys Tyr Ile Asn Leu Gly Ala Arg Trp Ser Leu
515 520 525
Asp Tyr Met Asp Asn Val Asn Pro Phe Asn His His Arg Asn Ala Gly
530 535 540
Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg Tyr Val Pro Phe
545 550 555 560
His Ile Gln Val Pro Gln Lys Phe Phe Ala Ile Lys Asn Leu Leu Leu
565 570 575
Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg Lys Asp Val Asn
580 585 590
Met Val Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg Val Asp Gly Ala
595 600 605
Ser Ile Lys Phe Glu Ser Ile Cys Leu Tyr Ala Thr Phe Phe Pro Met
610 615 620
Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu Arg Asn Asp Thr
625 630 635 640
Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala Asn Met Leu Tyr
645 650 655
Pro Ile Pro Ala Asn Ala Thr Asn Val Pro Ile Ser Ile Pro Ser Arg
660 665 670
Asn Trp Ala Ala Phe Arg Gly Trp Ala Phe Thr Arg Leu Lys Thr Lys
675 680 685
Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr Tyr Thr Tyr Ser
690 695 700
Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu Asn His Thr Phe
705 710 715 720
Lys Lys Val Ser Val Thr Phe Asp Ser Ser Val Ser Trp Pro Gly Asn
725 730 735
Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys Arg Ser Val Asp
740 745 750
Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr Lys Asp Trp Phe
755 760 765
Leu Val Gln Met Leu Ala Asn Tyr Asn Ile Gly Tyr Gln Gly Phe Tyr
770 775 780
Ile Pro Glu Ser Tyr Lys Asp Arg Met Tyr Ser Phe Phe Arg Asn Phe
785 790 795 800
Gln Pro Met Ser Arg Gln Val Val Asp Gln Thr Lys Tyr Lys Asp Tyr
805 810 815
Gln Glu Val Gly Ile Ile His Gln His Asn Asn Ser Gly Phe Val Gly
820 825 830
Tyr Leu Ala Pro Thr Met Arg Glu Gly Gln Ala Tyr Pro Ala Asn Phe
835 840 845
Pro Tyr Pro Leu Ile Gly Lys Thr Ala Val Asp Ser Ile Thr Gln Lys
850 855 860
Lys Phe Leu Cys Asp Arg Thr Leu Trp Arg Ile Pro Phe Ser Ser Asn
865 870 875 880
Phe Met Ser Met Gly Ala Leu Thr Asp Leu Gly Gln Asn Leu Leu Tyr
885 890 895
Ala Asn Ser Ala His Ala Leu Asp Met Thr Phe Glu Val Asp Pro Met
900 905 910
Asp Glu Pro Thr Leu Leu Tyr Val Leu Phe Glu Val Phe Asp Val Val
915 920 925
Arg Val His Gln Pro His Arg Gly Val Ile Glu Thr Val Tyr Leu Arg
930 935 940
Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr
945 950
<210> 43
<211> 210
<212> PRT
<213> Simian adenovirus 31
<400> 43
Met Pro Ser Gly Ser Thr Glu Gln Glu Leu Arg Ala Ile Val Arg Asp
1 5 10 15
Leu Gly Cys Gly Pro Tyr Phe Leu Gly Thr Phe Asp Lys Arg Phe Pro
20 25 30
Gly Phe Val Ser Pro His Lys Leu Ala Cys Ala Ile Val Asn Thr Ala
35 40 45
Gly Arg Glu Thr Gly Gly Val His Trp Leu Ala Phe Ala Trp Asn Pro
50 55 60
Arg Ser Lys Thr Cys Phe Leu Phe Asp Pro Phe Gly Phe Ser Asp Gln
65 70 75 80
Arg Leu Lys Gln Ile Tyr Glu Phe Glu Tyr Glu Gly Leu Leu Arg Arg
85 90 95
Ser Ala Ile Ala Ser Ser Pro Asp Arg Cys Val Thr Leu Glu Lys Ser
100 105 110
Thr Gln Thr Val Gln Gly Pro Asp Ser Ala Ala Cys Gly Leu Phe Cys
115 120 125
Cys Met Phe Leu His Ala Phe Val His Trp Pro Gln Ser Pro Met Asp
130 135 140
Arg Asn Pro Thr Met Asn Leu Leu Thr Gly Val Pro Asn Ser Met Leu
145 150 155 160
Gln Ser Pro Gln Val Glu Pro Thr Leu Arg Arg Asn Gln Glu Gln Leu
165 170 175
Tyr Ser Phe Leu Glu Arg His Ser Pro Tyr Phe Arg Arg His Ser Ala
180 185 190
Gln Ile Arg Arg Ala Thr Ser Phe Cys His Leu Gln Glu Met Gln Glu
195 200 205
Gly Lys
210
<210> 44
<211> 832
<212> PRT
<213> Simian adenovirus 31
<400> 44
Met Glu Ser Leu Met Gln Val Glu Lys Glu Glu Asp Ser Leu Thr Ala
1 5 10 15
Pro Ser Glu Pro Thr Thr Ala Ala Thr Ala Ala Ala Ser Ala Ala Ala
20 25 30
Asp Asp Ala Pro Thr Glu Thr Thr Thr Thr Thr Thr Thr Leu Pro Ser
35 40 45
Asp Ala Pro Pro Leu Glu Lys Glu Val Leu Ile Glu Gln Asp Pro Gly
50 55 60
Phe Val Ser Glu Glu Glu Asp Glu Ala Asp Glu Lys Glu Asp Thr Ala
65 70 75 80
Ala Ser Val Pro Lys Glu Asp Lys Lys Gln Asp Gln Asp Asp Ala Glu
85 90 95
Lys Asp Glu Ala Ala Val Gly Arg Gly Asp Gly Ser His Asp Ala Asp
100 105 110
Asp Gly Tyr Leu Asp Val Gly Asp Asp Val Leu Leu Lys His Leu His
115 120 125
Arg Gln Cys Val Ile Ile Cys Asp Ala Leu Gln Glu Arg Cys Glu Val
130 135 140
Pro Leu Asp Val Ala Glu Val Ser Arg Ala Tyr Glu Arg His Leu Phe
145 150 155 160
Ala Pro His Val Pro Pro Lys Arg Arg Glu Asn Gly Thr Cys Glu Pro
165 170 175
Asn Pro Arg Leu Asn Phe Tyr Pro Val Phe Ala Val Pro Glu Val Leu
180 185 190
Ala Thr Tyr His Ile Phe Phe Gln Asn Cys Lys Ile Pro Leu Ser Cys
195 200 205
Arg Ala Asn Arg Thr Arg Ala Asp Lys Thr Leu Thr Met Arg Gln Gly
210 215 220
Ala His Ile Pro Asp Ile Thr Ser Leu Glu Glu Val Pro Lys Ile Phe
225 230 235 240
Glu Gly Leu Gly Arg Asp Glu Lys Arg Ala Ala Asn Ala Leu His Gly
245 250 255
Asp Ser Glu Asn Glu Ser His Ser Gly Val Leu Val Glu Leu Glu Gly
260 265 270
Asp Asn Ala Arg Leu Ala Val Leu Lys Arg Ser Ile Glu Val Thr His
275 280 285
Phe Ala Tyr Pro Ala Leu Asn Leu Pro Pro Lys Val Met Ser Val Val
290 295 300
Met Gly Glu Leu Ile Met Arg Arg Ala Gln Pro Leu Asp Ala Asp Ala
305 310 315 320
Asn Leu Gln Glu Ser Ser Glu Glu Gly Leu Pro Ala Val Ser Asp Glu
325 330 335
Gln Leu Ala Arg Trp Leu Glu Thr Arg Asp Pro Ala Gln Leu Glu Glu
340 345 350
Arg Arg Lys Leu Met Met Ala Ala Val Leu Val Thr Val Glu Leu Glu
355 360 365
Cys Leu Gln Arg Phe Phe Ala Asp Pro Glu Met Gln Arg Lys Leu Glu
370 375 380
Glu Thr Leu His Tyr Thr Phe Arg Gln Gly Tyr Val Arg Gln Ala Cys
385 390 395 400
Lys Ile Ser Asn Val Glu Leu Cys Asn Leu Val Ser Tyr Leu Gly Ile
405 410 415
Leu His Glu Asn Arg Leu Gly Gln Asn Val Leu His Ser Thr Leu Arg
420 425 430
Gly Glu Ala Arg Arg Asp Tyr Ile Arg Asp Cys Val Tyr Leu Phe Leu
435 440 445
Cys Tyr Thr Trp Gln Thr Ala Met Gly Val Trp Gln Gln Cys Leu Glu
450 455 460
Glu Arg Asn Leu Lys Glu Leu Glu Lys Leu Leu Arg Arg Ala Leu Arg
465 470 475 480
Asp Leu Trp Thr Gly Phe Asn Glu Arg Ser Val Ala Ala Ala Leu Ala
485 490 495
Asp Ile Ile Phe Pro Glu Arg Leu Leu Lys Thr Leu Gln Gln Gly Leu
500 505 510
Pro Asp Phe Thr Ser Gln Ser Met Leu Gln Asn Phe Arg Thr Phe Ile
515 520 525
Leu Glu Arg Ser Gly Ile Leu Pro Ala Thr Cys Cys Ala Leu Pro Ser
530 535 540
Asp Phe Val Pro Ile Lys Tyr Arg Glu Cys Pro Pro Pro Leu Trp Gly
545 550 555 560
His Cys Tyr Leu Phe Gln Leu Ala Asn Tyr Leu Ala His His Ser Asp
565 570 575
Leu Met Glu Asp Val Ser Gly Glu Gly Leu Leu Glu Cys His Cys Arg
580 585 590
Cys Asn Leu Cys Thr Pro His Arg Ser Leu Val Cys Asn Pro Gln Leu
595 600 605
Leu Ser Glu Ser Gln Ile Ile Gly Thr Phe Glu Leu Gln Gly Pro Ser
610 615 620
Pro Asp Glu Lys Ser Ala Ala Pro Gly Leu Lys Leu Thr Pro Gly Leu
625 630 635 640
Trp Thr Ser Ala Tyr Leu Arg Lys Phe Val Pro Glu Asp Tyr His Ala
645 650 655
His Glu Ile Arg Phe Tyr Glu Asp Gln Ser Arg Pro Pro Lys Ala Glu
660 665 670
Leu Thr Ala Cys Val Ile Thr Gln Gly His Ile Leu Gly Gln Leu Gln
675 680 685
Ala Ile Asn Lys Ala Arg Gln Glu Phe Leu Leu Lys Lys Gly Arg Gly
690 695 700
Val Tyr Leu Asp Pro Gln Ser Gly Glu Glu Leu Asn Pro Leu Pro Pro
705 710 715 720
Pro Pro Pro Gln Gln Arg Asp Leu Ala Ser Gln Asp Gly Thr Gln Lys
725 730 735
Glu Ala Ala Ala Ala Ala Ala Ala Ala Ser Ala Leu His Ala Ser Gly
740 745 750
Gly Arg Gly Gly Leu Gly Gln Ser Gly Arg Gly Gly Phe Gly Arg Gly
755 760 765
Gly Gly Asp Asp Gly Arg Leu Gly Gly Gly Gln Gln Pro Arg Arg Gly
770 775 780
Ser Phe Arg Gly Arg Arg Gly Gly Arg Arg Asn Thr Ile Thr Leu Gly
785 790 795 800
Arg Ser Pro Leu Ala Gly Ala Pro Glu Val Leu Arg Ala Gln His Gln
805 810 815
Arg Tyr Asn Leu Arg Ser Ser Gly Ala Thr Arg Pro Gln Thr Gln Pro
820 825 830
<210> 45
<211> 227
<212> PRT
<213> Simian adenovirus 31
<400> 45
Met Ser Lys Glu Ile Pro Thr Pro Tyr Met Trp Ser Tyr Gln Pro Gln
1 5 10 15
Met Gly Val Ala Ala Gly Ala Ala Gln Asp Tyr Ser Thr Arg Met Asn
20 25 30
Tyr Met Ser Ala Gly Pro His Met Ile Ser Arg Val Asn Gly Ile Arg
35 40 45
Ala Gln Arg Asn Gln Ile Leu Leu Glu Gln Ala Ala Ile Thr Ala Thr
50 55 60
Pro Arg His Asn Leu Asn Pro Arg Asn Trp Pro Ala Ala Leu Val Tyr
65 70 75 80
Gln Glu Thr Pro Ser Ala Thr Thr Val Leu Leu Pro Arg Asp Ala Gln
85 90 95
Ala Glu Val Gln Met Thr Asn Ser Gly Ala Gln Leu Ala Gly Gly Phe
100 105 110
Arg His Gly Ala Arg Pro His Arg Gln Gly Ile Leu His Leu Ala Ile
115 120 125
Arg Gly Arg Gly Ile Gln Leu Asn Asp Glu Ser Val Ser Ser Ser Leu
130 135 140
Gly Leu Arg Pro Asp Gly Thr Phe Gln Leu Ala Gly Ala Gly Arg Ser
145 150 155 160
Ser Phe Thr Pro Arg Gln Ala Tyr Leu Thr Leu Gln Thr Ser Ser Ser
165 170 175
Glu Pro Arg Ser Gly Gly Ile Gly Thr Leu Gln Phe Val Glu Glu Phe
180 185 190
Val Pro Ser Val Tyr Phe Asn Pro Phe Ser Gly Pro Pro Gly Arg Tyr
195 200 205
Pro Asp Gln Phe Ile Pro Asn Phe Asp Ala Val Lys Asp Ser Ala Asp
210 215 220
Gly Tyr Asp
225
<210> 46
<211> 105
<212> PRT
<213> Simian adenovirus 31
<400> 46
Met Ser Gly Ala Glu Ala Glu Arg Leu Arg Leu Lys His Leu Glu His
1 5 10 15
Cys Arg Arg His Asn Cys Phe Ala Arg Gly Ser Gly Glu Phe Cys Tyr
20 25 30
Phe Gln Leu Pro Glu Glu His Thr Glu Gly Pro Ala His Gly Val Arg
35 40 45
Leu Thr Thr Gln Gly Glu Val Thr Cys Ser Leu Ile Arg Glu Phe Thr
50 55 60
Leu Arg Pro Leu Leu Val Glu Arg Glu Arg Gly Pro Cys Val Leu Thr
65 70 75 80
Ile Ala Cys Asn Cys Pro Asn Pro Gly Leu His Gln Asp Leu Cys Cys
85 90 95
His Leu Cys Ala Glu Phe Asn Lys Arg
100 105
<210> 47
<211> 166
<212> PRT
<213> Simian adenovirus 31
<400> 47
Met Asn Arg Tyr Thr Ile Leu Thr Ile Leu Gly Leu Leu Ala Leu Ala
1 5 10 15
Ala Cys Ser Ala Ala Thr Lys Lys Glu Val Thr Phe Glu Glu Pro Ala
20 25 30
Cys Asn Val Thr Phe Lys Pro Glu Gly Ala His Cys Thr Thr Leu Val
35 40 45
Lys Cys Val Thr Lys His Glu Arg Leu Arg Ile Asp Tyr Lys Asn Met
50 55 60
Thr Gly Arg Tyr Ala Val Tyr Ser Ile Phe Thr Pro Gly Asp Pro Ser
65 70 75 80
Asn Tyr Ser Val Thr Val Phe Glu Gly Gly Gln Phe Lys Lys Phe Asp
85 90 95
Tyr Thr Phe Pro Phe Tyr Glu Leu Cys Asp Ala Val Met Tyr Met Ser
100 105 110
Lys Gln Tyr Asn Leu Trp Pro Pro Thr Pro Gln Ala Cys Val Glu Asn
115 120 125
Thr Gly Ser Phe Cys Cys Val Ala Phe Leu Ile Thr Ala Val Ala Leu
130 135 140
Ile Cys Thr Leu Leu Tyr Ile Lys Phe Arg Gln Arg Arg Ile Phe Ile
145 150 155 160
Asp Glu Lys Lys Met Pro
165
<210> 48
<211> 291
<212> PRT
<213> Simian adenovirus 31
<400> 48
Met Asn Ala Ile Thr Thr Ser Leu Leu Ile Thr Thr Thr Leu Leu Ala
1 5 10 15
Ile Ala His Gly Leu Thr Arg Ile Glu Val Pro Val Gly Ser Asn Val
20 25 30
Thr Met Val Gly Pro Ala Gly Asn Ser Thr Leu Met Trp Glu Lys Phe
35 40 45
Val Arg Asn Gln Trp Val His Phe Cys Ser Asn Arg Ile Ser Ile Lys
50 55 60
Pro Arg Ala Ile Cys Asp Gly Gln Asn Leu Thr Leu Ile Asp Val Gln
65 70 75 80
Met Met Asp Ala Gly Tyr Tyr Tyr Gly Gln Arg Gly Glu Ile Ile Asn
85 90 95
Tyr Trp Arg Pro His Lys Asp Tyr Met Leu His Val Val Glu Ala Val
100 105 110
Pro Thr Thr Ser Pro Thr Thr Thr Thr Thr Thr Thr Thr Thr Thr Ser
115 120 125
Thr Thr Ala Ala Arg His Thr Arg Lys Ser Thr Met Ile Ser Thr Lys
130 135 140
Pro Pro Pro Ala His Ser His Ala Gly Gly Pro Ile Gly Ala Thr Ser
145 150 155 160
Glu Thr Thr Glu Leu Cys Phe Cys Gln Cys Thr Asn Ala Ser Ala His
165 170 175
Glu Leu Phe Asp Leu Glu Asn Glu Asp Ala Gln Gln Ser Ser Ala Cys
180 185 190
Pro Ala Pro Ala Ala Val Glu Pro Val Ala Leu Lys Gln Ile Gly Asp
195 200 205
Ser Ser Ile Ile Asp Phe Ser Ala Thr Pro Glu Tyr Pro Pro Asp Ser
210 215 220
Thr Phe His Ile Thr Gly Thr Lys Asp Pro Asn Leu Ser Phe Tyr Leu
225 230 235 240
Met Leu Leu Leu Cys Ile Ser Val Val Ser Ser Ala Leu Met Leu Leu
245 250 255
Gly Met Phe Cys Cys Leu Ile Cys Arg Arg Lys Arg Lys Ala Arg Ser
260 265 270
Gln Gly Gln Pro Leu Met Pro Phe Pro Tyr Pro Pro Asp Phe Ala Asp
275 280 285
Asn Lys Ile
290
<210> 49
<211> 90
<212> PRT
<213> Simian adenovirus 31
<400> 49
Met Pro Arg Ile Phe Leu Tyr Leu Leu Leu Ile Pro Pro Phe Leu Gly
1 5 10 15
Cys Ser Thr Leu Ala Ala Val Ser His Leu Glu Val Asp Cys Leu Gln
20 25 30
Pro Phe Ala Val Tyr Leu Leu Tyr Gly Leu Val Thr Leu Thr Leu Ile
35 40 45
Cys Ser Leu Ile Thr Val Ile Ile Ala Phe Ile Gln Cys Ile Asp Tyr
50 55 60
Ile Cys Val Arg Leu Ala Tyr Phe Arg His His Pro Gln Tyr Arg Asp
65 70 75 80
Arg Asn Ile Ala Gln Leu Leu Arg Leu Leu
85 90
<210> 50
<211> 132
<212> PRT
<213> Simian adenovirus 31
<400> 50
Met His Lys Thr Val Ile Cys Leu Leu Ile Leu Cys Thr Leu Pro Ala
1 5 10 15
Phe Thr Ser Cys Gln Tyr Thr Thr Lys Ala Pro Arg Lys Arg His Ala
20 25 30
Ser Cys Arg Phe Thr Gln Leu Trp Asn Ile Pro Lys Cys Tyr Asn Glu
35 40 45
Lys Ser Glu Leu Ser Glu Ala Trp Leu Tyr Gly Val Ile Cys Val Leu
50 55 60
Val Phe Cys Ser Thr Val Phe Ala Leu Met Ile Tyr Pro His Ile Asp
65 70 75 80
Leu Gly Trp Asn Ala Ile Asp Ala Met Ser Tyr Pro Thr Phe Pro Ala
85 90 95
Pro Glu Met Ile Pro Leu Arg Gln Val Val Pro Val Val Val Asn Gln
100 105 110
Arg Pro Pro Ser Pro Thr Pro Thr Glu Ile Ser Tyr Phe Asn Leu Thr
115 120 125
Gly Gly Asp Asp
130
<210> 51
<211> 596
<212> PRT
<213> Simian adenovirus 31
<400> 51
Met Ser Asp Ser Cys Ser Cys Pro Ser Ala Pro Thr Ile Phe Met Leu
1 5 10 15
Leu Gln Met Lys Arg Thr Lys Thr Ser Asp Glu Ser Phe Asn Pro Val
20 25 30
Tyr Pro Tyr Asp Thr Glu Asn Gly Pro Pro Ser Val Pro Phe Leu Thr
35 40 45
Pro Pro Phe Val Ser Pro Asp Gly Phe Gln Glu Ser Pro Pro Gly Val
50 55 60
Leu Ser Leu Asn Leu Ala Glu Pro Leu Val Thr Ser His Gly Met Leu
65 70 75 80
Ala Leu Lys Met Gly Ser Gly Leu Ser Leu Asp Asp Ala Gly Asn Leu
85 90 95
Thr Ser Gln Asp Val Thr Thr Thr Thr Pro Pro Leu Lys Lys Thr Lys
100 105 110
Thr Asn Leu Ser Leu Glu Thr Ser Ala Pro Leu Thr Val Ser Thr Ser
115 120 125
Gly Ala Leu Thr Leu Ala Ala Ala Ala Pro Leu Ala Val Ala Gly Thr
130 135 140
Ser Leu Thr Met Gln Ser Glu Ala Pro Leu Thr Val Gln Asp Ala Lys
145 150 155 160
Leu Thr Leu Ala Thr Lys Gly Pro Leu Thr Val Ser Glu Gly Lys Leu
165 170 175
Ala Leu Gln Thr Ser Ala Pro Leu Thr Ala Ala Asp Ser Ser Thr Leu
180 185 190
Thr Val Ser Ala Thr Pro Pro Leu Ser Thr Ser Asn Gly Ser Leu Gly
195 200 205
Ile Asp Met Gln Ala Pro Ile Tyr Thr Thr Asn Gly Lys Leu Gly Leu
210 215 220
Asn Phe Gly Ala Pro Leu His Val Val Asp Ser Leu Asn Ala Leu Thr
225 230 235 240
Val Val Thr Gly Gln Gly Leu Thr Ile Asn Gly Thr Ala Leu Gln Thr
245 250 255
Arg Val Ser Gly Ala Leu Asn Tyr Asp Ser Ser Gly Asn Leu Glu Leu
260 265 270
Arg Ala Ala Gly Gly Met Arg Val Asp Ala Asn Gly Lys Leu Ile Leu
275 280 285
Asp Val Ala Tyr Pro Phe Asp Ala Gln Asn Asn Leu Ser Leu Arg Leu
290 295 300
Gly Gln Gly Pro Leu Phe Val Asn Ser Ala His Asn Leu Asp Val Asn
305 310 315 320
Tyr Asn Arg Gly Leu Tyr Leu Phe Thr Ser Gly Asn Thr Lys Lys Leu
325 330 335
Glu Val Asn Ile Lys Thr Ala Lys Gly Leu Ile Tyr Asp Asp Thr Ala
340 345 350
Ile Ala Ile Asn Pro Gly Asp Gly Leu Glu Phe Gly Ser Gly Ser Asp
355 360 365
Thr Asn Pro Leu Lys Thr Lys Leu Gly Leu Gly Leu Glu Tyr Asp Ser
370 375 380
Ser Arg Ala Ile Ile Ala Lys Leu Gly Thr Gly Leu Ser Phe Asp Asn
385 390 395 400
Thr Gly Ala Ile Thr Val Gly Asn Asn Asn Asp Asp Lys Leu Thr Leu
405 410 415
Trp Thr Thr Pro Asp Pro Ser Pro Asn Cys Arg Ile Tyr Ser Glu Lys
420 425 430
Asp Ala Lys Phe Thr Leu Val Leu Thr Lys Cys Gly Ser Gln Val Leu
435 440 445
Ala Ser Val Ser Val Leu Ser Val Lys Gly Ser Leu Ala Pro Ile Ser
450 455 460
Gly Thr Val Thr Ser Ala Gln Ile Ile Leu Arg Phe Asn Glu Asn Gly
465 470 475 480
Val Leu Leu Ser Asn Ser Ser Leu Asp Pro Gln Tyr Trp Asn Tyr Arg
485 490 495
Lys Gly Asp Leu Thr Glu Gly Thr Ala Tyr Thr Asn Ala Val Gly Phe
500 505 510
Met Pro Asn Leu Thr Ala Tyr Pro Lys Thr Gln Ser Gln Thr Ala Lys
515 520 525
Ser Asn Ile Val Ser Gln Val Tyr Leu Asn Gly Asp Lys Ser Lys Pro
530 535 540
Met Ile Leu Thr Ile Thr Leu Asn Gly Thr Asn Glu Thr Gly Asp Ala
545 550 555 560
Thr Val Ser Thr Tyr Ser Met Ser Phe Ser Trp Asn Trp Asn Gly Ser
565 570 575
Asn Tyr Ile Asn Glu Thr Phe Gln Thr Asn Ser Phe Thr Phe Ser Tyr
580 585 590
Ile Ala Gln Glu
595
<210> 52
<211> 570
<212> DNA
<213> Simian adenovirus 31
<220>
<221> CDS
<222> (8)..(568)
<223> label=Elb\19K
<400> 52
tgacctc atg gag gcc tgg gag tgt ttg gag agc ttt gcc gga gtg cgt 49
Met Glu Ala Trp Glu Cys Leu Glu Ser Phe Ala Gly Val Arg
1 5 10
gcc ttg ctg gac gag agc tct aac aat acc tct ggg tgg tgg agg tat 97
Ala Leu Leu Asp Glu Ser Ser Asn Asn Thr Ser Gly Trp Trp Arg Tyr
15 20 25 30
ttg tgg ggc tct ccc cag ggc aag tta gtt tgt agg atc aag gag gat 145
Leu Trp Gly Ser Pro Gln Gly Lys Leu Val Cys Arg Ile Lys Glu Asp
35 40 45
tac aag tgg gaa ttt gaa gag ctt ttg aaa tcc tgt ggt gag cta ttg 193
Tyr Lys Trp Glu Phe Glu Glu Leu Leu Lys Ser Cys Gly Glu Leu Leu
50 55 60
gat tct ttg aat cta ggc cac cag gct ctt ttc cag gag aag gtc atc 241
Asp Ser Leu Asn Leu Gly His Gln Ala Leu Phe Gln Glu Lys Val Ile
65 70 75
agg act ttg gat ttt tcc aca ccg ggg cgc gtt gca gcc ggg gtt gct 289
Arg Thr Leu Asp Phe Ser Thr Pro Gly Arg Val Ala Ala Gly Val Ala
80 85 90
ttt cta gct ttt ttg aag gat aaa tgg agc gaa gag acc cac ttg agt 337
Phe Leu Ala Phe Leu Lys Asp Lys Trp Ser Glu Glu Thr His Leu Ser
95 100 105 110
tcg ggc tac gtc ctg gat ttt ctg gcc atg caa ctg tgg agg gca tgg 385
Ser Gly Tyr Val Leu Asp Phe Leu Ala Met Gln Leu Trp Arg Ala Trp
115 120 125
atc agg cac aag aac agg ctg caa ctg ttg tct acc gtc cgc ccg ctg 433
Ile Arg His Lys Asn Arg Leu Gln Leu Leu Ser Thr Val Arg Pro Leu
130 135 140
ctg att ccg gcg gag gag caa cag gcc ggg tca gag gac cgg gcc cgt 481
Leu Ile Pro Ala Glu Glu Gln Gln Ala Gly Ser Glu Asp Arg Ala Arg
145 150 155
cgg gat ccg gag cag ggg gcg ccg agg ccg ggc gag agg agc gcg tgg 529
Arg Asp Pro Glu Gln Gly Ala Pro Arg Pro Gly Glu Arg Ser Ala Trp
160 165 170
aac ctg gga acc ggg ctg agc ggc cat cca cat cgg gag tg 570
Asn Leu Gly Thr Gly Leu Ser Gly His Pro His Arg Glu
175 180 185
<210> 53
<211> 187
<212> PRT
<213> Simian adenovirus 31
<400> 53
Met Glu Ala Trp Glu Cys Leu Glu Ser Phe Ala Gly Val Arg Ala Leu
1 5 10 15
Leu Asp Glu Ser Ser Asn Asn Thr Ser Gly Trp Trp Arg Tyr Leu Trp
20 25 30
Gly Ser Pro Gln Gly Lys Leu Val Cys Arg Ile Lys Glu Asp Tyr Lys
35 40 45
Trp Glu Phe Glu Glu Leu Leu Lys Ser Cys Gly Glu Leu Leu Asp Ser
50 55 60
Leu Asn Leu Gly His Gln Ala Leu Phe Gln Glu Lys Val Ile Arg Thr
65 70 75 80
Leu Asp Phe Ser Thr Pro Gly Arg Val Ala Ala Gly Val Ala Phe Leu
85 90 95
Ala Phe Leu Lys Asp Lys Trp Ser Glu Glu Thr His Leu Ser Ser Gly
100 105 110
Tyr Val Leu Asp Phe Leu Ala Met Gln Leu Trp Arg Ala Trp Ile Arg
115 120 125
His Lys Asn Arg Leu Gln Leu Leu Ser Thr Val Arg Pro Leu Leu Ile
130 135 140
Pro Ala Glu Glu Gln Gln Ala Gly Ser Glu Asp Arg Ala Arg Arg Asp
145 150 155 160
Pro Glu Gln Gly Ala Pro Arg Pro Gly Glu Arg Ser Ala Trp Asn Leu
165 170 175
Gly Thr Gly Leu Ser Gly His Pro His Arg Glu
180 185
<210> 54
<211> 6010
<212> DNA
<213> Simian adenovirus 31
<220>
<221> CDS
<222> (7)..(600)
<223> label=22K
<220>
<221> CDS
<222> (1982)..(2521)
<223> label=E3\CR1\alpha
<220>
<221> CDS
<222> (4100)..(4939)
<223> label=E3\CR1\gamma
<220>
<221> CDS
<222> (5620)..(6003)
<223> label=E3\14.7K
<400> 54
cccagg atg gca ccc aga aag aag cag cag cag ccg ccg ccg cag cct 48
Met Ala Pro Arg Lys Lys Gln Gln Gln Pro Pro Pro Gln Pro
1 5 10
cag ccc tac atg ctt ctg gag gaa gag gag gac tgg gac agt cag gca 96
Gln Pro Tyr Met Leu Leu Glu Glu Glu Glu Asp Trp Asp Ser Gln Ala
15 20 25 30
gag gag gtt tcg gac gag gag gag gag atg atg gaa gac tgg gag gag 144
Glu Glu Val Ser Asp Glu Glu Glu Glu Met Met Glu Asp Trp Glu Glu
35 40 45
gac agc agc cta gac gag gaa gct tca gag gcc gaa gag gtg gca gac 192
Asp Ser Ser Leu Asp Glu Glu Ala Ser Glu Ala Glu Glu Val Ala Asp
50 55 60
gca aca cca tca ccc tcg gtc gca gcc ccc tcg ccg ggg ccc ctg aag 240
Ala Thr Pro Ser Pro Ser Val Ala Ala Pro Ser Pro Gly Pro Leu Lys
65 70 75
tcc tcc gag ccc agc atc agc gct ata acc tcc gct cct ccg gcg cca 288
Ser Ser Glu Pro Ser Ile Ser Ala Ile Thr Ser Ala Pro Pro Ala Pro
80 85 90
ccc ggc cgc aga ccc aac cgt aga tgg gac acc aca gga acc ggg gtc 336
Pro Gly Arg Arg Pro Asn Arg Arg Trp Asp Thr Thr Gly Thr Gly Val
95 100 105 110
ggt aag tca aag tgc cca ccg ccg cca ccc ccc tcg cag cag cag cgc 384
Gly Lys Ser Lys Cys Pro Pro Pro Pro Pro Pro Ser Gln Gln Gln Arg
115 120 125
cag ggc tac cgc tcg tgg cgc ggg cac aag aac gcc ata gtc gcc tgc 432
Gln Gly Tyr Arg Ser Trp Arg Gly His Lys Asn Ala Ile Val Ala Cys
130 135 140
ttg caa gac tgc ggg ggc aac atc tcc ttc gcc cgc cgc ttc ctg ctc 480
Leu Gln Asp Cys Gly Gly Asn Ile Ser Phe Ala Arg Arg Phe Leu Leu
145 150 155
ttc cac cac ggg gtc gcc ttc ccc cgc aat gtc ctg cat tac tac cgt 528
Phe His His Gly Val Ala Phe Pro Arg Asn Val Leu His Tyr Tyr Arg
160 165 170
cat ctc tac agc ccc tac tgc ggc agc ggc gac cca gag gcg gca gcg 576
His Leu Tyr Ser Pro Tyr Cys Gly Ser Gly Asp Pro Glu Ala Ala Ala
175 180 185 190
tca gcc gca gcg gag acc acc agc taggaagacc tcatcctccg cgggcaagac 630
Ser Ala Ala Ala Glu Thr Thr Ser
195
ggcggcagcg gccaggagac ccgcggcggc tgcggcgacg ggagcggtgg gcgcactgcg 690
cctctcgccc aacgaacccc tctcgacccg ggagctcaga cacaggatct tccccactct 750
gtatgccatc ttccaacaga gcagaggcca ggagcaggag ctgaaaataa aaaacagatc 810
tctgcgctcc ctcacccgca gctgtctgta tcacaaaagc gaagatcagc ttcggcgcac 870
gctagaggac gcggaggcac tcttcagcaa atactgcgcg ctcactctta aggactagct 930
ccgcgccctt ctcgaattta ggcgggagaa aactacgtca tcgccggccg ccgcccagcc 990
cgcccagccg acatgagcaa agagattccc acgccataca tgtggagcta ccagccgcag 1050
atgggagtcg cggcgggagc ggcccaggac tactccaccc gcatgaacta catgagcgcg 1110
ggaccccaca tgatctcacg ggtcaacggt atccgcgccc agcgaaacca aatactgctg 1170
gaacaggcgg ccatcaccgc cacgccccgt cataatctca acccccgaaa ttggcccgcc 1230
gccctcgtgt accaggaaac cccctctgcc accaccgtac tacttccgcg tgacgcccag 1290
gccgaagtcc agatgactaa ctcaggggcg cagctcgcgg gcggctttcg tcacggggcg 1350
aggccgcacc ggcagggtat attacacctg gcgatcagag gccgaggtat tcagctcaac 1410
gacgagtcgg tgagctcttc gctcggtctc cgtccggacg gaaccttcca gctcgccgga 1470
gccggccgct cttcgttcac gccccgccag gcgtacctga ctctgcagac ctcgtcctcg 1530
gagcctcgct ccggcggcat cgggaccctc cagttcgtgg aggagttcgt gccctcggtc 1590
tacttcaacc ccttctcggg acctcccgga cgctaccccg accagttcat cccgaacttt 1650
gacgcggtga aggactcagc ggacggctac gactgaatgt caggtgccga ggcagagcgg 1710
cttcgcctga aacacctcga gcactgccgc cgccacaact gcttcgcccg cggctccggt 1770
gagttctgct actttcagct acccgaggag cataccgaag ggccggcgca cggcgtccgc 1830
ctgaccaccc agggcgaggt tacctgttcc ctcatccggg agttcaccct ccgtcccctg 1890
ctagtggagc gggagcgggg tccctgtgtc ctaactatcg cctgcaactg ccctaaccct 1950
ggattacatc aagatctttg ctgtcatctc t gtg ctg agt tta ata aac gct 2002
Val Leu Ser Leu Ile Asn Ala
200 205
gag atc aga atc tac tgg ggc tcc tgt cgc cat cct ctg aac gcc acc 2050
Glu Ile Arg Ile Tyr Trp Gly Ser Cys Arg His Pro Leu Asn Ala Thr
210 215 220
gtc ttc acc cac ccc gac cag gcc cag gcg aac ctc acc tgc ggt ctg 2098
Val Phe Thr His Pro Asp Gln Ala Gln Ala Asn Leu Thr Cys Gly Leu
225 230 235
cat cgg agg gcc agg aag tac ctc acc tgg tac ttc aac ggc acc ccc 2146
His Arg Arg Ala Arg Lys Tyr Leu Thr Trp Tyr Phe Asn Gly Thr Pro
240 245 250
ttt gtg gtt tac aac agc ttc gac ggg gac gga gtc tcc ctg aaa gac 2194
Phe Val Val Tyr Asn Ser Phe Asp Gly Asp Gly Val Ser Leu Lys Asp
255 260 265
cag ctc tcc ggt ctc agc tac tcc atc cac aag aac acc acc ctc caa 2242
Gln Leu Ser Gly Leu Ser Tyr Ser Ile His Lys Asn Thr Thr Leu Gln
270 275 280 285
ctc ttc cct ccc tac ctg ccg gga acc tac gag tgc gtc acc ggc cgc 2290
Leu Phe Pro Pro Tyr Leu Pro Gly Thr Tyr Glu Cys Val Thr Gly Arg
290 295 300
tgc acc cac ctc acc cgc ctg atc gta aac cag agc ttt ccg gga aca 2338
Cys Thr His Leu Thr Arg Leu Ile Val Asn Gln Ser Phe Pro Gly Thr
305 310 315
gat aac tcc ctc ttc ccc aga aca gga ggt gag ctc agg aaa ctc ccc 2386
Asp Asn Ser Leu Phe Pro Arg Thr Gly Gly Glu Leu Arg Lys Leu Pro
320 325 330
ggg gac cag ggc gga gac cta cct tcg acc ctt gtg ggg tta gga ttt 2434
Gly Asp Gln Gly Gly Asp Leu Pro Ser Thr Leu Val Gly Leu Gly Phe
335 340 345
ttt att acc ggg ttg ctg gct gtt tta atc aaa gct tcc ttg aga ttt 2482
Phe Ile Thr Gly Leu Leu Ala Val Leu Ile Lys Ala Ser Leu Arg Phe
350 355 360 365
atc ctc tcc att tac gtg tat gaa cac ctc agc ctc cag taactctacc 2531
Ile Leu Ser Ile Tyr Val Tyr Glu His Leu Ser Leu Gln
370 375
ctttcttcgg aatcaggtga cttttctgaa atcgggctcg gtgtgctgct tactctgttg 2591
atttttttcc ttatcatact cagccttctg tgcctcaggc tcgccgcctg ctgcgcacat 2651
atctacatct actgctggtt gctcaagtgc aggggtcgcc acccaagatg aacaggtaca 2711
caattctaac catcctaggc ctgctggccc tggcggcctg cagcgccgcc accaaaaaag 2771
aggttacctt tgaggagccc gcttgcaatg taaccttcaa gcccgagggt gcgcattgta 2831
ccaccctggt caaatgcgtt accaagcatg agaggttgcg catcgactac aaaaacatga 2891
ctggcaggta tgcggtctat agtatcttta cgcccggaga cccctctaac tactctgtca 2951
ccgtctttga gggcggtcag tttaagaaat tcgattacac tttccccttt tatgagttgt 3011
gcgatgcggt catgtacatg tcaaaacagt acaacctgtg gccccccact ccccaggcgt 3071
gtgtggaaaa tactgggtct ttctgctgtg tggctttcct aatcactgca gtcgctctaa 3131
tctgcacgct gctatatatc aaattcaggc agaggcgaat ctttatcgat gaaaagaaaa 3191
tgccttgatc gctaacaccg gctttctatc tgcagaatga atgcaatcac cacctcccta 3251
ctaatcacca ccaccctcct tgcgattgcc catgggttga cacgaatcga agtgccagtg 3311
gggtccaatg tcaccatggt gggccccgcc ggcaattcca ccctcatgtg ggaaaaattt 3371
gtccgcaatc aatgggttca tttctgctct aaccgaatca gtatcaagcc cagagccatc 3431
tgcgatgggc aaaatctaac cctgatcgat gtgcaaatga tggatgccgg gtactattac 3491
gggcagcggg gagagattat taattactgg cgaccccaca aggactacat gctgcatgta 3551
gtcgaggcag ttcccactac ctcccccact accaccacta ccactaccac taccacctcc 3611
actaccgctg cccgccatac ccgcaaaagc accatgatta gcacaaagcc ccctcctgct 3671
cactcccacg ccggcgggcc catcggtgcg acctcagaaa ccaccgagct ttgcttctgc 3731
caatgcacta acgccagcgc tcatgaactg ttcgacctgg agaatgagga tgcccagcag 3791
agctccgctt gcccggcccc ggcggctgtg gagcccgttg ccctgaagca gatcggtgat 3851
tcttcgataa ttgacttttc tgccactccc gaataccctc ccgattctac cttccacatc 3911
acgggtacca aagaccctaa cctctctttc tacctgatgc tgctgctctg tatctctgtg 3971
gtctcttccg cgctgatgtt actggggatg ttctgctgcc tgatctgccg cagaaagaga 4031
aaagctcgct ctcagggcca accactgatg cccttcccct accccccgga ttttgcagat 4091
aacaagat atg agc tcg ctg ctg aca cta acc gct tta cta gcc tgc gct 4141
Met Ser Ser Leu Leu Thr Leu Thr Ala Leu Leu Ala Cys Ala
380 385 390
gct cta acc ctt gtc gct tgc gaa tcc aga ttc cac aat gtc aca gtt 4189
Ala Leu Thr Leu Val Ala Cys Glu Ser Arg Phe His Asn Val Thr Val
395 400 405
gtg gca gga gaa aat gtt aca ttc aac tcc acg gcc gac gcc cgg tgg 4237
Val Ala Gly Glu Asn Val Thr Phe Asn Ser Thr Ala Asp Ala Arg Trp
410 415 420
tcg tgg agt ggc tcc ggt agc tac cta gat atc tgc aat agc tcc act 4285
Ser Trp Ser Gly Ser Gly Ser Tyr Leu Asp Ile Cys Asn Ser Ser Thr
425 430 435 440
tcc tct agc ata acc cca gcc aag tac caa tgc aat gcc acc ctg ttc 4333
Ser Ser Ser Ile Thr Pro Ala Lys Tyr Gln Cys Asn Ala Thr Leu Phe
445 450 455
acc ctc atc aac gcc tcc acc ctg gac aat gga ctc tat gta ggc tac 4381
Thr Leu Ile Asn Ala Ser Thr Leu Asp Asn Gly Leu Tyr Val Gly Tyr
460 465 470
gta ccc ccc ggt ggg caa gga aag acc cac gct tac aac ctg gaa gtg 4429
Val Pro Pro Gly Gly Gln Gly Lys Thr His Ala Tyr Asn Leu Glu Val
475 480 485
cgc cag ccc aga acc act acc cag cct tcc ccc agc acc acc acc acc 4477
Arg Gln Pro Arg Thr Thr Thr Gln Pro Ser Pro Ser Thr Thr Thr Thr
490 495 500
acc agc agc agc agc aac aga agc aga ttc ctg act ttc att ttg gcc 4525
Thr Ser Ser Ser Ser Asn Arg Ser Arg Phe Leu Thr Phe Ile Leu Ala
505 510 515 520
agc tca tcc gcc gcc acc gct cag acc acc cag gcc atc tac acc tct 4573
Ser Ser Ser Ala Ala Thr Ala Gln Thr Thr Gln Ala Ile Tyr Thr Ser
525 530 535
gtg ccc gaa acc act cag acc cac cgc cca gag acg acc acc gcc acc 4621
Val Pro Glu Thr Thr Gln Thr His Arg Pro Glu Thr Thr Thr Ala Thr
540 545 550
acc cca cac acc tcc acc gac cgg atg ccg gcc aac atc gcc ccc ttg 4669
Thr Pro His Thr Ser Thr Asp Arg Met Pro Ala Asn Ile Ala Pro Leu
555 560 565
gct ctt cag aat gga ctt aca agc tcc act cca aaa cca gtg gat gca 4717
Ala Leu Gln Asn Gly Leu Thr Ser Ser Thr Pro Lys Pro Val Asp Ala
570 575 580
gcc gaa gtc tcc gcc ctc gtc aat gac tgg gcg ggg ctg gga atg tgg 4765
Ala Glu Val Ser Ala Leu Val Asn Asp Trp Ala Gly Leu Gly Met Trp
585 590 595 600
tgg ttc gcc ata ggc atg atg gcg ctc tgc ctg ctt ctg ctc tgg ctc 4813
Trp Phe Ala Ile Gly Met Met Ala Leu Cys Leu Leu Leu Leu Trp Leu
605 610 615
atc tgc tgc ctc cac cgc agg cga gcc aga ccc ccc atc tat aga ccc 4861
Ile Cys Cys Leu His Arg Arg Arg Ala Arg Pro Pro Ile Tyr Arg Pro
620 625 630
atc att gtc ctc aac ccc gat aat gat ggg atc cat aga ttg gat ggc 4909
Ile Ile Val Leu Asn Pro Asp Asn Asp Gly Ile His Arg Leu Asp Gly
635 640 645
ctg aaa aac cta ctt ttt tct ttt aca gta tgataaattg agacatgcct 4959
Leu Lys Asn Leu Leu Phe Ser Phe Thr Val
650 655
cgcattttct tgtacttgct ccttatccca ccttttctgg ggtgttctac gctggccgct 5019
gtgtctcacc tggaggtaga ctgtctccag cccttcgctg tctacctgct ttacggactg 5079
gtcaccctca ctctcatctg cagcctaatc acagtaatca tcgccttcat ccagtgcatt 5139
gattacatct gtgtgcgcct cgcatacttc agacaccacc cacagtaccg agacaggaac 5199
attgcccaac ttctaagact tctctaatca tgcataagac cgtgatctgc ctcctgatcc 5259
tctgcaccct gcccgccttc acctcctgcc agtacaccac aaaagctccg cgcaaaagac 5319
atgcctcctg ccgcttcacc caactgtgga atatccccaa atgctacaac gaaaagagcg 5379
agctctccga agcctggctg tatggggtta tctgtgtctt agttttctgc agcactgtct 5439
ttgccctgat gatctacccc cacattgatt tgggatggaa cgcgatcgat gccatgagtt 5499
accccacctt tcccgcgccc gagatgattc cactgcgaca ggtcgtaccc gttgtcgtca 5559
atcaacgccc cccatcccct acgcccactg agatcagcta ctttaatcta acaggcggag 5619
atg act gac gcc cta gat cta gaa atg gac ggc atc agt acc gag cag 5667
Met Thr Asp Ala Leu Asp Leu Glu Met Asp Gly Ile Ser Thr Glu Gln
660 665 670
cgt ctc cta gag agg cgc agg cag gcg gtt gag caa gag cgc ctc aat 5715
Arg Leu Leu Glu Arg Arg Arg Gln Ala Val Glu Gln Glu Arg Leu Asn
675 680 685 690
cag gag ctc cga gat ctc ctt aac ctg cac cag tgc aaa aga ggc atc 5763
Gln Glu Leu Arg Asp Leu Leu Asn Leu His Gln Cys Lys Arg Gly Ile
695 700 705
ttt tgc ctg gcc aag cag gcc aaa gtc acc tac gag aag acc ggt aac 5811
Phe Cys Leu Ala Lys Gln Ala Lys Val Thr Tyr Glu Lys Thr Gly Asn
710 715 720
agc cac cgc ctc agt tac aaa ttg ccc acc cag cgc cag aag ctg gtg 5859
Ser His Arg Leu Ser Tyr Lys Leu Pro Thr Gln Arg Gln Lys Leu Val
725 730 735
ctc atg gtg ggt gag aat ccc atc acc gtc acc cag cac tcg gta gaa 5907
Leu Met Val Gly Glu Asn Pro Ile Thr Val Thr Gln His Ser Val Glu
740 745 750
acc gag ggg tgt ctg cac tcc ccc tgt cgg ggt cca gaa gac ctc tgc 5955
Thr Glu Gly Cys Leu His Ser Pro Cys Arg Gly Pro Glu Asp Leu Cys
755 760 765 770
acc ctg gtg aag acc ctg tgc ggt ctc aga gat tta gtc ccc ttt aac 6003
Thr Leu Val Lys Thr Leu Cys Gly Leu Arg Asp Leu Val Pro Phe Asn
775 780 785
taatcaa 6010
<210> 55
<211> 198
<212> PRT
<213> Simian adenovirus 31
<400> 55
Met Ala Pro Arg Lys Lys Gln Gln Gln Pro Pro Pro Gln Pro Gln Pro
1 5 10 15
Tyr Met Leu Leu Glu Glu Glu Glu Asp Trp Asp Ser Gln Ala Glu Glu
20 25 30
Val Ser Asp Glu Glu Glu Glu Met Met Glu Asp Trp Glu Glu Asp Ser
35 40 45
Ser Leu Asp Glu Glu Ala Ser Glu Ala Glu Glu Val Ala Asp Ala Thr
50 55 60
Pro Ser Pro Ser Val Ala Ala Pro Ser Pro Gly Pro Leu Lys Ser Ser
65 70 75 80
Glu Pro Ser Ile Ser Ala Ile Thr Ser Ala Pro Pro Ala Pro Pro Gly
85 90 95
Arg Arg Pro Asn Arg Arg Trp Asp Thr Thr Gly Thr Gly Val Gly Lys
100 105 110
Ser Lys Cys Pro Pro Pro Pro Pro Pro Ser Gln Gln Gln Arg Gln Gly
115 120 125
Tyr Arg Ser Trp Arg Gly His Lys Asn Ala Ile Val Ala Cys Leu Gln
130 135 140
Asp Cys Gly Gly Asn Ile Ser Phe Ala Arg Arg Phe Leu Leu Phe His
145 150 155 160
His Gly Val Ala Phe Pro Arg Asn Val Leu His Tyr Tyr Arg His Leu
165 170 175
Tyr Ser Pro Tyr Cys Gly Ser Gly Asp Pro Glu Ala Ala Ala Ser Ala
180 185 190
Ala Ala Glu Thr Thr Ser
195
<210> 56
<211> 180
<212> PRT
<213> Simian adenovirus 31
<400> 56
Val Leu Ser Leu Ile Asn Ala Glu Ile Arg Ile Tyr Trp Gly Ser Cys
1 5 10 15
Arg His Pro Leu Asn Ala Thr Val Phe Thr His Pro Asp Gln Ala Gln
20 25 30
Ala Asn Leu Thr Cys Gly Leu His Arg Arg Ala Arg Lys Tyr Leu Thr
35 40 45
Trp Tyr Phe Asn Gly Thr Pro Phe Val Val Tyr Asn Ser Phe Asp Gly
50 55 60
Asp Gly Val Ser Leu Lys Asp Gln Leu Ser Gly Leu Ser Tyr Ser Ile
65 70 75 80
His Lys Asn Thr Thr Leu Gln Leu Phe Pro Pro Tyr Leu Pro Gly Thr
85 90 95
Tyr Glu Cys Val Thr Gly Arg Cys Thr His Leu Thr Arg Leu Ile Val
100 105 110
Asn Gln Ser Phe Pro Gly Thr Asp Asn Ser Leu Phe Pro Arg Thr Gly
115 120 125
Gly Glu Leu Arg Lys Leu Pro Gly Asp Gln Gly Gly Asp Leu Pro Ser
130 135 140
Thr Leu Val Gly Leu Gly Phe Phe Ile Thr Gly Leu Leu Ala Val Leu
145 150 155 160
Ile Lys Ala Ser Leu Arg Phe Ile Leu Ser Ile Tyr Val Tyr Glu His
165 170 175
Leu Ser Leu Gln
180
<210> 57
<211> 280
<212> PRT
<213> Simian adenovirus 31
<400> 57
Met Ser Ser Leu Leu Thr Leu Thr Ala Leu Leu Ala Cys Ala Ala Leu
1 5 10 15
Thr Leu Val Ala Cys Glu Ser Arg Phe His Asn Val Thr Val Val Ala
20 25 30
Gly Glu Asn Val Thr Phe Asn Ser Thr Ala Asp Ala Arg Trp Ser Trp
35 40 45
Ser Gly Ser Gly Ser Tyr Leu Asp Ile Cys Asn Ser Ser Thr Ser Ser
50 55 60
Ser Ile Thr Pro Ala Lys Tyr Gln Cys Asn Ala Thr Leu Phe Thr Leu
65 70 75 80
Ile Asn Ala Ser Thr Leu Asp Asn Gly Leu Tyr Val Gly Tyr Val Pro
85 90 95
Pro Gly Gly Gln Gly Lys Thr His Ala Tyr Asn Leu Glu Val Arg Gln
100 105 110
Pro Arg Thr Thr Thr Gln Pro Ser Pro Ser Thr Thr Thr Thr Thr Ser
115 120 125
Ser Ser Ser Asn Arg Ser Arg Phe Leu Thr Phe Ile Leu Ala Ser Ser
130 135 140
Ser Ala Ala Thr Ala Gln Thr Thr Gln Ala Ile Tyr Thr Ser Val Pro
145 150 155 160
Glu Thr Thr Gln Thr His Arg Pro Glu Thr Thr Thr Ala Thr Thr Pro
165 170 175
His Thr Ser Thr Asp Arg Met Pro Ala Asn Ile Ala Pro Leu Ala Leu
180 185 190
Gln Asn Gly Leu Thr Ser Ser Thr Pro Lys Pro Val Asp Ala Ala Glu
195 200 205
Val Ser Ala Leu Val Asn Asp Trp Ala Gly Leu Gly Met Trp Trp Phe
210 215 220
Ala Ile Gly Met Met Ala Leu Cys Leu Leu Leu Leu Trp Leu Ile Cys
225 230 235 240
Cys Leu His Arg Arg Arg Ala Arg Pro Pro Ile Tyr Arg Pro Ile Ile
245 250 255
Val Leu Asn Pro Asp Asn Asp Gly Ile His Arg Leu Asp Gly Leu Lys
260 265 270
Asn Leu Leu Phe Ser Phe Thr Val
275 280
<210> 58
<211> 128
<212> PRT
<213> Simian adenovirus 31
<400> 58
Met Thr Asp Ala Leu Asp Leu Glu Met Asp Gly Ile Ser Thr Glu Gln
1 5 10 15
Arg Leu Leu Glu Arg Arg Arg Gln Ala Val Glu Gln Glu Arg Leu Asn
20 25 30
Gln Glu Leu Arg Asp Leu Leu Asn Leu His Gln Cys Lys Arg Gly Ile
35 40 45
Phe Cys Leu Ala Lys Gln Ala Lys Val Thr Tyr Glu Lys Thr Gly Asn
50 55 60
Ser His Arg Leu Ser Tyr Lys Leu Pro Thr Gln Arg Gln Lys Leu Val
65 70 75 80
Leu Met Val Gly Glu Asn Pro Ile Thr Val Thr Gln His Ser Val Glu
85 90 95
Thr Glu Gly Cys Leu His Ser Pro Cys Arg Gly Pro Glu Asp Leu Cys
100 105 110
Thr Leu Val Lys Thr Leu Cys Gly Leu Arg Asp Leu Val Pro Phe Asn
115 120 125
<210> 59
<211> 980
<212> DNA
<213> Simian adenovirus 31
<220>
<221> CDS
<222> (6)..(546)
<223> label=Ela
<220>
<221> CDS
<222> (670)..(971)
<223> label=Ela
<400> 59
gaaaa atg aga cat ttc acc tac gat ggc ggt gtg ctc acc ggc cag ctg 50
Met Arg His Phe Thr Tyr Asp Gly Gly Val Leu Thr Gly Gln Leu
1 5 10 15
gct gct cag gtc ctg gac acc ctg atc gag gag gta ttg gct gat aat 98
Ala Ala Gln Val Leu Asp Thr Leu Ile Glu Glu Val Leu Ala Asp Asn
20 25 30
tat cct ccc gcg act cct ttc gac gca cct acc ctt cac gaa ctg tat 146
Tyr Pro Pro Ala Thr Pro Phe Asp Ala Pro Thr Leu His Glu Leu Tyr
35 40 45
gat ctg gag gtg gtg ggg ccc aac gat ccg aac gag cag gcg gtt tcc 194
Asp Leu Glu Val Val Gly Pro Asn Asp Pro Asn Glu Gln Ala Val Ser
50 55 60
gaa ttt ttt ccc gag tcc atg ttg ttg gcc agc cag gag ggg gtc gaa 242
Glu Phe Phe Pro Glu Ser Met Leu Leu Ala Ser Gln Glu Gly Val Glu
65 70 75
ctt cag acc cct cct ccg atc acc gtt tcc ccc gat ccg ccg ccg ctg 290
Leu Gln Thr Pro Pro Pro Ile Thr Val Ser Pro Asp Pro Pro Pro Leu
80 85 90 95
agt agg cag ccc gag cgc tgc gtg gga cct gcg act atg ccc cag ctg 338
Ser Arg Gln Pro Glu Arg Cys Val Gly Pro Ala Thr Met Pro Gln Leu
100 105 110
ctg cct gag gtg atc gat ctc acc tgt aac gag tct ggt ttt cca ccc 386
Leu Pro Glu Val Ile Asp Leu Thr Cys Asn Glu Ser Gly Phe Pro Pro
115 120 125
agc gag gat gag gac gaa gag ggt gag cag ttt gtg tta gat tct gtg 434
Ser Glu Asp Glu Asp Glu Glu Gly Glu Gln Phe Val Leu Asp Ser Val
130 135 140
gat caa ccc ggg cga gga tgc agg tct tgt caa tat cac cgg aga aac 482
Asp Gln Pro Gly Arg Gly Cys Arg Ser Cys Gln Tyr His Arg Arg Asn
145 150 155
aca gga gac ccc cag att atg tgt tct ctg tgt tat atg aag atg acc 530
Thr Gly Asp Pro Gln Ile Met Cys Ser Leu Cys Tyr Met Lys Met Thr
160 165 170 175
tgt atg ttt att tac a gtaagtttgt gatcggtggg caggtgggct atagtgtggg 586
Cys Met Phe Ile Tyr
180
tgggtggtct ttgtggtgtt ttttttttta atatatgtta gggggttatg ctaaatactt 646
tcttattgtg atttttttaa aag gt cca gtg tct gag ccc gag cag gaa cct 698
Ser Pro Val Ser Glu Pro Glu Gln Glu Pro
185 190
gag ccg gag cct gag cct cct cgc ccc agg aga aag cct gca att tta 746
Glu Pro Glu Pro Glu Pro Pro Arg Pro Arg Arg Lys Pro Ala Ile Leu
195 200 205
act aga ccc agc gca ccg gta gcg agg ggc ctc agc agt gcg gag acc 794
Thr Arg Pro Ser Ala Pro Val Ala Arg Gly Leu Ser Ser Ala Glu Thr
210 215 220
acc gac tcc ggc gct tcc gca cca tcc cct ccg gag att cat cct gtg 842
Thr Asp Ser Gly Ala Ser Ala Pro Ser Pro Pro Glu Ile His Pro Val
225 230 235
gtg ccc ctg tgt ccc att aag ccc gtt gcc gtg aga gtt agt ggg cgg 890
Val Pro Leu Cys Pro Ile Lys Pro Val Ala Val Arg Val Ser Gly Arg
240 245 250
cgg tct gct gtg gag tgc att gag gac ttg ctt ttt gaa tca cag gaa 938
Arg Ser Ala Val Glu Cys Ile Glu Asp Leu Leu Phe Glu Ser Gln Glu
255 260 265 270
cct ttg gac ttg agc ttg aaa cgc ccc agg cat tagacctgg 980
Pro Leu Asp Leu Ser Leu Lys Arg Pro Arg His
275 280
<210> 60
<211> 281
<212> PRT
<213> Simian adenovirus 31
<400> 60
Met Arg His Phe Thr Tyr Asp Gly Gly Val Leu Thr Gly Gln Leu Ala
1 5 10 15
Ala Gln Val Leu Asp Thr Leu Ile Glu Glu Val Leu Ala Asp Asn Tyr
20 25 30
Pro Pro Ala Thr Pro Phe Asp Ala Pro Thr Leu His Glu Leu Tyr Asp
35 40 45
Leu Glu Val Val Gly Pro Asn Asp Pro Asn Glu Gln Ala Val Ser Glu
50 55 60
Phe Phe Pro Glu Ser Met Leu Leu Ala Ser Gln Glu Gly Val Glu Leu
65 70 75 80
Gln Thr Pro Pro Pro Ile Thr Val Ser Pro Asp Pro Pro Pro Leu Ser
85 90 95
Arg Gln Pro Glu Arg Cys Val Gly Pro Ala Thr Met Pro Gln Leu Leu
100 105 110
Pro Glu Val Ile Asp Leu Thr Cys Asn Glu Ser Gly Phe Pro Pro Ser
115 120 125
Glu Asp Glu Asp Glu Glu Gly Glu Gln Phe Val Leu Asp Ser Val Asp
130 135 140
Gln Pro Gly Arg Gly Cys Arg Ser Cys Gln Tyr His Arg Arg Asn Thr
145 150 155 160
Gly Asp Pro Gln Ile Met Cys Ser Leu Cys Tyr Met Lys Met Thr Cys
165 170 175
Met Phe Ile Tyr Ser Pro Val Ser Glu Pro Glu Gln Glu Pro Glu Pro
180 185 190
Glu Pro Glu Pro Pro Arg Pro Arg Arg Lys Pro Ala Ile Leu Thr Arg
195 200 205
Pro Ser Ala Pro Val Ala Arg Gly Leu Ser Ser Ala Glu Thr Thr Asp
210 215 220
Ser Gly Ala Ser Ala Pro Ser Pro Pro Glu Ile His Pro Val Val Pro
225 230 235 240
Leu Cys Pro Ile Lys Pro Val Ala Val Arg Val Ser Gly Arg Arg Ser
245 250 255
Ala Val Glu Cys Ile Glu Asp Leu Leu Phe Glu Ser Gln Glu Pro Leu
260 265 270
Asp Leu Ser Leu Lys Arg Pro Arg His
275 280
<210> 61
<211> 930
<212> DNA
<213> Simian adenovirus 31
<220>
<221> CDS
<222> (7)..(333)
<223> label=33K
<220>
<221> CDS
<222> (629)..(925)
<223> label=33K
<400> 61
cccagg atg gca ccc aga aag aag cag cag cag ccg ccg ccg cag cct 48
Met Ala Pro Arg Lys Lys Gln Gln Gln Pro Pro Pro Gln Pro
1 5 10
cag ccc tac atg ctt ctg gag gaa gag gag gac tgg gac agt cag gca 96
Gln Pro Tyr Met Leu Leu Glu Glu Glu Glu Asp Trp Asp Ser Gln Ala
15 20 25 30
gag gag gtt tcg gac gag gag gag gag atg atg gaa gac tgg gag gag 144
Glu Glu Val Ser Asp Glu Glu Glu Glu Met Met Glu Asp Trp Glu Glu
35 40 45
gac agc agc cta gac gag gaa gct tca gag gcc gaa gag gtg gca gac 192
Asp Ser Ser Leu Asp Glu Glu Ala Ser Glu Ala Glu Glu Val Ala Asp
50 55 60
gca aca cca tca ccc tcg gtc gca gcc ccc tcg ccg ggg ccc ctg aag 240
Ala Thr Pro Ser Pro Ser Val Ala Ala Pro Ser Pro Gly Pro Leu Lys
65 70 75
tcc tcc gag ccc agc atc agc gct ata acc tcc gct cct ccg gcg cca 288
Ser Ser Glu Pro Ser Ile Ser Ala Ile Thr Ser Ala Pro Pro Ala Pro
80 85 90
ccc ggc cgc aga ccc aac cgt aga tgg gac acc aca gga acc ggg 333
Pro Gly Arg Arg Pro Asn Arg Arg Trp Asp Thr Thr Gly Thr Gly
95 100 105
gtcggtaagt caaagtgccc accgccgcca cccccctcgc agcagcagcg ccagggctac 393
cgctcgtggc gcgggcacaa gaacgccata gtcgcctgct tgcaagactg cgggggcaac 453
atctccttcg cccgccgctt cctgctcttc caccacgggg tcgccttccc ccgcaatgtc 513
ctgcattact accgtcatct ctacagcccc tactgcggca gcggcgaccc agaggcggca 573
gcgtcagccg cagcggagac caccagctag gaagacctca tcctccgcgg gcaag acg 631
Thr
110
gcg gca gcg gcc agg aga ccc gcg gcg gct gcg gcg acg gga gcg gtg 679
Ala Ala Ala Ala Arg Arg Pro Ala Ala Ala Ala Ala Thr Gly Ala Val
115 120 125
ggc gca ctg cgc ctc tcg ccc aac gaa ccc ctc tcg acc cgg gag ctc 727
Gly Ala Leu Arg Leu Ser Pro Asn Glu Pro Leu Ser Thr Arg Glu Leu
130 135 140
aga cac agg atc ttc ccc act ctg tat gcc atc ttc caa cag agc aga 775
Arg His Arg Ile Phe Pro Thr Leu Tyr Ala Ile Phe Gln Gln Ser Arg
145 150 155
ggc cag gag cag gag ctg aaa ata aaa aac aga tct ctg cgc tcc ctc 823
Gly Gln Glu Gln Glu Leu Lys Ile Lys Asn Arg Ser Leu Arg Ser Leu
160 165 170
acc cgc agc tgt ctg tat cac aaa agc gaa gat cag ctt cgg cgc acg 871
Thr Arg Ser Cys Leu Tyr His Lys Ser Glu Asp Gln Leu Arg Arg Thr
175 180 185 190
cta gag gac gcg gag gca ctc ttc agc aaa tac tgc gcg ctc act ctt 919
Leu Glu Asp Ala Glu Ala Leu Phe Ser Lys Tyr Cys Ala Leu Thr Leu
195 200 205
aag gac tagct 930
Lys Asp
<210> 62
<211> 208
<212> PRT
<213> Simian adenovirus 31
<400> 62
Met Ala Pro Arg Lys Lys Gln Gln Gln Pro Pro Pro Gln Pro Gln Pro
1 5 10 15
Tyr Met Leu Leu Glu Glu Glu Glu Asp Trp Asp Ser Gln Ala Glu Glu
20 25 30
Val Ser Asp Glu Glu Glu Glu Met Met Glu Asp Trp Glu Glu Asp Ser
35 40 45
Ser Leu Asp Glu Glu Ala Ser Glu Ala Glu Glu Val Ala Asp Ala Thr
50 55 60
Pro Ser Pro Ser Val Ala Ala Pro Ser Pro Gly Pro Leu Lys Ser Ser
65 70 75 80
Glu Pro Ser Ile Ser Ala Ile Thr Ser Ala Pro Pro Ala Pro Pro Gly
85 90 95
Arg Arg Pro Asn Arg Arg Trp Asp Thr Thr Gly Thr Gly Thr Ala Ala
100 105 110
Ala Ala Arg Arg Pro Ala Ala Ala Ala Ala Thr Gly Ala Val Gly Ala
115 120 125
Leu Arg Leu Ser Pro Asn Glu Pro Leu Ser Thr Arg Glu Leu Arg His
130 135 140
Arg Ile Phe Pro Thr Leu Tyr Ala Ile Phe Gln Gln Ser Arg Gly Gln
145 150 155 160
Glu Gln Glu Leu Lys Ile Lys Asn Arg Ser Leu Arg Ser Leu Thr Arg
165 170 175
Ser Cys Leu Tyr His Lys Ser Glu Asp Gln Leu Arg Arg Thr Leu Glu
180 185 190
Asp Ala Glu Ala Leu Phe Ser Lys Tyr Cys Ala Leu Thr Leu Lys Asp
195 200 205
<210> 63
<211> 37799
<212> DNA
<213> Simian adenovirus 34
<220>
<221> repeat_region
<222> (1)..(119)
<223> label=ITR
<220>
<221> CDS
<222> (1640)..(2275)
<223> label=Elb\19K
<220>
<221> CDS
<222> (3637)..(4101)
<223> label=pIX
<220>
<221> misc_feature
<222> (4166)..(5790)
<223> complement (4166..5499, 5778..5790) label=IVa2
<220>
<221> misc_feature
<222> (5272)..(114220)
<223> complement (5272..8847, 14212..14220) label=pol
<220>
<221> misc_feature
<222> (8649)..(14220)
<223> complement (8649..10649, 14212..14220) label=pTP
<220>
<221> CDS
<222> (11102)..(12358)
<223> label=52K
<220>
<221> CDS
<222> (12385)..(14160)
<223> label=pIIIa
<220>
<221> CDS
<222> (14185)..(16035)
<223> label=penton
<220>
<221> CDS
<222> (16053)..(16646)
<223> label=pVII
<220>
<221> CDS
<222> (16722)..(17834)
<223> label=V
<220>
<221> CDS
<222> (17862)..(18104)
<223> label=pX
<220>
<221> CDS
<222> (18197)..(18949)
<223> label=pVI
<220>
<221> CDS
<222> (19064)..(21937)
<223> label=hexon
<220>
<221> CDS
<222> (21970)..(22596)
<223> label=protease
<220>
<221> misc_feature
<222> (22713)..(24362)
<223> complement label=DBP
<220>
<221> CDS
<222> (26597)..(27193)
<223> label=22K
<220>
<221> CDS
<222> (27593)..(28273)
<223> label=pVIII
<220>
<221> CDS
<222> (28277)..(28591)
<223> label=E3\12.5K
<220>
<221> CDS
<222> (29211)..(29783)
<223> label=E3\gp19K
<220>
<221> CDS
<222> (29815)..(30693)
<223> label=E3\CR1\beta
<220>
<221> CDS
<222> (31556)..(31825)
<223> label=E3\RID\alpha
<220>
<221> CDS
<222> (31831)..(32226)
<223> label=E3\RID\beta
<220>
<221> CDS
<222> (32760)..(34547)
<223> label=fiber
<220>
<221> misc_feature
<222> (34758)..(35888)
<223> complement (34758..35030, 35733..35888) label=E4\orf6/7
<220>
<221> misc_feature
<222> (35034)..(35888)
<223> complement label=E4\orf6
<220>
<221> misc_feature
<222> (35818)..(36180)
<223> complement label=E4\orf4
<220>
<221> misc_feature
<222> (36200)..(36544)
<223> complement label=E4\orf3
<220>
<221> misc_feature
<222> (36544)..(36993)
<223> complement label=E4\orf2
<220>
<221> misc_feature
<222> (36989)..(37372)
<223> complement label=E4\orf1
<220>
<221> repeat_region
<222> (37681)..(37799)
<223> complement label=ITR
<400> 63
catcatcaat aatatacctt attttggatt gaagccaata tgataatgag atgggcggcg 60
cggggcgggg cgcggggcgg gaggcgggtt tgggggcggg ccggcgggcg gggaggtgtg 120
gcggaagtgg actttgtaag tgtggcggat gtgacttgct agtgccgggc gcggtaaaag 180
tgacgttttc cgtgcgcgac aacgcccacg ggaagtgaca tttttcccgc ggtttttacc 240
ggatgttgta gtgaatttgg gcgtaaccaa gtaagatttg gtcattttcg cgggaaaact 300
gaaacgggga agtgaaatct gattaatttc gcgttagtca taccgcgtaa tatttgtcga 360
gggccgaggg actttggccg attacgtgga ggactcgccc aggtgttttt tgaggtgaat 420
ttccgcgttc cgggtcaaag tctccgtttt attattatag tcagctgacg cggagtgtat 480
ttataccctc tgatctcgtc aagaggccac tcttgagtgc cagcgagtag agttttctcc 540
tctgccgctc tccgctccgc tccgctcggc tctgacaccg gggaaaaaat gagacatttc 600
acctacgatg gcggtgtgct caccggccag ctggctgctg aggtcctgga caccctgatc 660
gaggaggtat tggccgataa ttatcctccc tcgactcctt ttgagccacc tacacttcac 720
gaactctacg atctggatgt ggtggggccc agcgatccga acgagcaggc ggtttccagt 780
ttttttccag agtccatgtt gttggccagc caggaggggg tcgaacttga gacccctcct 840
ccgatcgtgg attcccccga tccgccgcag ctgactaggc agcccgagcg ctgtgcggga 900
cctgagacta tgccccagct gctacctgag gtgatcgatc tcacctgtaa tgagtctggt 960
tttccaccca gcgaggatga ggacgaagag ggtgagcagt ttgtgttaga ttctgtggaa 1020
caacccgggc gaggatgcag gtcttgtcaa tatcaccgga aaaacacagg agactcccag 1080
attatgtgtt ctctgtgtta tatgaagatg acctgtatgt ttatttacag taagtttatc 1140
atcggtgggc aggtgggcta tagtgtgggt ggtggtcttt gggggttttt taatatatgt 1200
caggggttat gctgaagact tttttattgt gatttttaaa ggtccagtgt ctgagcccga 1260
gcaagaacct gaaccggagc ctgagccttc tcgccccagg agaaagcctg tgatcttaac 1320
tagacccagc gcaccggtag cgagaggcct cagcagcgcg gagaccaccg actccggtgc 1380
ttcctcatca cccccggaga ttcaccccct ggtgcccctg tgtcccgtta agcccgttgc 1440
cgtgagagtc agtgggcggc ggtctgctgt ggagtgcatt gaggacttgc tttttgattc 1500
acaggaacct ttggacttga gcttgaaacg ccccaggcat taaacctggt cacctggact 1560
gaatgagttg acgcctatgt ttgcttttga atgacttaat gtgtatagat aataaagagt 1620
gagataatgt tttaattgc atg gtg tgt tta act tgg gcg gag tct gct ggg 1672
Met Val Cys Leu Thr Trp Ala Glu Ser Ala Gly
1 5 10
tat ata agc ttc cct ggg cta aac ttg gtt aca ctt gac ctc atg gag 1720
Tyr Ile Ser Phe Pro Gly Leu Asn Leu Val Thr Leu Asp Leu Met Glu
15 20 25
gcc tgg gag tgt ttg gag aac ttt gcc gga gtt cgt gcc ttg ctg gac 1768
Ala Trp Glu Cys Leu Glu Asn Phe Ala Gly Val Arg Ala Leu Leu Asp
30 35 40
gag agc tct aac aat acc tct tgg tgg tgg agg tat ttg tgg ggc tct 1816
Glu Ser Ser Asn Asn Thr Ser Trp Trp Trp Arg Tyr Leu Trp Gly Ser
45 50 55
ccc cag ggc aag tta gtt tgt aga atc aag gag gat tac aag tgg gaa 1864
Pro Gln Gly Lys Leu Val Cys Arg Ile Lys Glu Asp Tyr Lys Trp Glu
60 65 70 75
ttt gaa gag ctt ttg aaa tcc tgt ggt gag cta ttg gat tct ttg aat 1912
Phe Glu Glu Leu Leu Lys Ser Cys Gly Glu Leu Leu Asp Ser Leu Asn
80 85 90
cta ggc cac cag gct ctc ttc cag gag aag gtc atc agg act ttg gat 1960
Leu Gly His Gln Ala Leu Phe Gln Glu Lys Val Ile Arg Thr Leu Asp
95 100 105
ttt tcc aca ccg ggg cgc att gca gcc gcg gtt gct ttt cta gct ttt 2008
Phe Ser Thr Pro Gly Arg Ile Ala Ala Ala Val Ala Phe Leu Ala Phe
110 115 120
ttg aag gat aga tgg agc gaa gag acc cac ttg agt tcg ggc tac gtc 2056
Leu Lys Asp Arg Trp Ser Glu Glu Thr His Leu Ser Ser Gly Tyr Val
125 130 135
ctg gat ttt ctg gcc atg caa ctg tgg aga gca tgg atc aga cac aag 2104
Leu Asp Phe Leu Ala Met Gln Leu Trp Arg Ala Trp Ile Arg His Lys
140 145 150 155
aac agg ctg caa ctg ttg tct tcc gtc cgc ccg ttg ctg att ccg gcg 2152
Asn Arg Leu Gln Leu Leu Ser Ser Val Arg Pro Leu Leu Ile Pro Ala
160 165 170
gag gag caa cag gcc ggg tca gag gac cgg gcc cgt cgg gat ccg gag 2200
Glu Glu Gln Gln Ala Gly Ser Glu Asp Arg Ala Arg Arg Asp Pro Glu
175 180 185
gag agg gca ccg agg ccg ggc gag agg agc gcg ccg aac ctg gga acc 2248
Glu Arg Ala Pro Arg Pro Gly Glu Arg Ser Ala Pro Asn Leu Gly Thr
190 195 200
ggg ctg agc ggc cat cca cat cgg gag tgaatgtcgg gcaggtggtg 2295
Gly Leu Ser Gly His Pro His Arg Glu
205 210
gatctttttc cagaactgcg gcggattttg actattaggg aggatgggca atttgttaag 2355
ggtcttaaga gggagagggg ggcttctgag cataacgagg aggccagtaa tttagctttt 2415
agcttgatga ccagacaccg tccagagtgc atcacttttc agcagattaa ggacaattgt 2475
gccaatgagt tggatctgtt gggtcagaag tatagcatag agcagctgac cacttactgg 2535
ctgcagccgg gtgatgatct ggaggaagct attagggtgt atgctaaggt ggccctgcgg 2595
cccgattgca agtacaagct caaggggctg gtgaatatca ggaattgttg ctacatttct 2655
ggcaacgggg cggaggtgga gatagagacc gaagacaggg tggctttcag atgcagcatg 2715
atgaatatgt ggccgggggt gctgggcatg gacggggtgg tgattatgaa tgtgaggttc 2775
acggggtcca actttaacgg cacggtgttt ttggggaaca ccaacctggt cctgcacggg 2835
gtgagcttct atgggtttaa caacacctgt gtggaggcct ggaccgatgt gaaggtccgc 2895
ggttgcgcct tttatggatg ttggaaggcc atagtgagcc gccctaagag caggagttcc 2955
attaagaaat gcttgtttga gaggtgcacc ttggggatcc tggccgaggg caactgcagg 3015
gtgcgccaca atgtggcctc cgagtgcggt tgcttcatgc tagtcaagag cgtggcggta 3075
atcaagcata atatggtgtg cggcaacagc gaggacaagg cctcacagat gctgacctgc 3135
acggatggca actgccactt gctgaagacc atccatgtaa ccagccacag ccggaaggcc 3195
tggcccgtgt tcgagcacaa cttgctgacc cgctgctcct tgcatctggg caacaggcgg 3255
ggggtgttcc tgccctatca atgcaacttt agtcacacca agatcttgct agagcccgag 3315
agcatgtcca aggtgaactt gaacggggtg tttgacatga ccatgaagat ctggaaggtg 3375
ctgaggtacg acgagaccag gtcccggtgc agaccctgcg agtgcggggg caagcatatg 3435
aggaaccagc ccgtgatgct ggatgtgacc gaggagctga ggacagacca cttggttctg 3495
gcctgcacca gggccgagtt tggttctagc gatgaagaca cagattgagg tgggtgagtg 3555
ggcgtggcct ggggtggtca tgaaaatata taagttgggg gtcttagggt ctctttattt 3615
gttgcagaga ccgccggagc c atg agc ggg agc agc agc agc agc agt agc 3666
Met Ser Gly Ser Ser Ser Ser Ser Ser Ser
215 220
agc agc agc gcc ttg gat ggc agc atc gtg agc cct tat ttg acg acg 3714
Ser Ser Ser Ala Leu Asp Gly Ser Ile Val Ser Pro Tyr Leu Thr Thr
225 230 235
cgg atg ccc cac tgg gcc ggg gtg cgt cag aat gtg atg ggc tcc agc 3762
Arg Met Pro His Trp Ala Gly Val Arg Gln Asn Val Met Gly Ser Ser
240 245 250
atc gac ggc cga ccc gtc ctg ccc gca aat tcc gcc acg ctg acc tat 3810
Ile Asp Gly Arg Pro Val Leu Pro Ala Asn Ser Ala Thr Leu Thr Tyr
255 260 265 270
gcg acc gtc gcg ggg acg ccg ttg gac gcc acc gcc gcc gcc gcc gcc 3858
Ala Thr Val Ala Gly Thr Pro Leu Asp Ala Thr Ala Ala Ala Ala Ala
275 280 285
acc gca gcc gcc tcg gcc gtg cgc agc ctg gcc acg gac ttt gca ttc 3906
Thr Ala Ala Ala Ser Ala Val Arg Ser Leu Ala Thr Asp Phe Ala Phe
290 295 300
ctg gga cca ctg gcg aca ggg gct act tct cgg gcc gct gct gcc gcc 3954
Leu Gly Pro Leu Ala Thr Gly Ala Thr Ser Arg Ala Ala Ala Ala Ala
305 310 315
gtt cgc gat gac aag ctg acc gcc ctg ctg gcg cag ttg gat gcg ctt 4002
Val Arg Asp Asp Lys Leu Thr Ala Leu Leu Ala Gln Leu Asp Ala Leu
320 325 330
act cgg gaa ctg ggt gac ctt tct cag cag gtc atg gcc ctg cgc cag 4050
Thr Arg Glu Leu Gly Asp Leu Ser Gln Gln Val Met Ala Leu Arg Gln
335 340 345 350
cag gtc tcc tcc ctg caa gct ggc ggg aat gct tct ccc aca aat gcc 4098
Gln Val Ser Ser Leu Gln Ala Gly Gly Asn Ala Ser Pro Thr Asn Ala
355 360 365
gtt taagataaat aaaaccagac tctgtttgga ttaaagaaaa gtagcaagtg 4151
Val
cattgctctc tttatttcat aattttccgc gcgcgatagg ccctagacca gcgttctcgg 4211
tcgttgaggg tgcggtgtat cttctccagg acgtggtaga ggtggctctg gacgttgaga 4271
tacatgggca tgagcccgtc ccgggggtgg aggtagcacc actgcagagc ttcatgctcc 4331
ggggtggtgt tgtagatgat ccagtcgtag caggagcgct gggcatggtg cctaaaaatg 4391
tccttcagca gcaggccgat ggccaggggg aggcccttgg tgtaagtgtt tacaaaacgg 4451
ttaagttggg aagggtgcat tcggggagag atgatgtgca tcttggactg tatttttaga 4511
ttggcgatgt ttccgcccag atcccttctg ggattcatgt tgtgcaggac caccagtaca 4571
gtgtatccgg tgcacttggg gaatttgtca tgcagcttag agggaaaagc gtggaagaac 4631
ttggagacgc ccttgtggcc tcccagattt tccatgcatt cgtccatgat gatggcaatg 4691
ggcccgcggg aggcagcttg ggcaaagata tttctggggt cgctgacgtc gtagttgtgt 4751
tccagggtga ggtcgtcata ggccattttt acaaagcgcg ggcggagggt gcccgactgg 4811
gggatgatgg tcccctctgg ccctggggcg tagttgccct cgcagatctg catttcccag 4871
gccttaatct cggagggggg aatcatatcc acctgcgggg cgatgaagaa aacggtttcc 4931
ggagccgggg agattaactg ggatgaaagc aggtttctaa gcagctgtga ttttccacaa 4991
ccggtgggcc cataaataac acctataacc ggttgcagct ggtagtttag agagctgcag 5051
ctgccgtcgt cccggaggag gggggccacc tcgttgagca tgtccctgac gcgcatgttc 5111
tccccgacca gatccgccag aaggcgctcg ccgcccaggg acagcagctc ttgcaaggaa 5171
gcaaagtttt tcagcggctt gaggccgtcc gccgtgggca tgtttttcag ggtctggctc 5231
agcagctcca ggcggtccca gagctcggtg acgtgctcta cggcatctct atccagcata 5291
tctcctcgtt tcgcgggttg gggcgacttt cgctgtaggg caccaagcgg tggtcgtcca 5351
gcggggccag agtcatgtcc ttccatgggc gcagggtcct cgtcagggtg gtctgggtca 5411
cggtgaaggg gtgcgctccg ggctgagcgc ttgccaaggt gcgcttgagg ctggttctgc 5471
tggtgctgaa gcgctgccgg tcttcgccct gcgcgtcggc caggtagcat ttgaccatgg 5531
tgtcatagtc cagcccctcc gcggcgtgtc ccttggcgcg cagcttgccc ttggaggtgg 5591
cgccgcacga ggggcagagc aggctcttga gcgcgtagag cttgggggcg aggaagaccg 5651
attcggggga gtaggcgtcc gcgccgcaga ccccgcacac ggtctcgcac tccaccagcc 5711
aggtgagctc ggggcgcgcc gggtcaaaaa ccaggtttcc cccatgcttt ttgatgcgtt 5771
tcttacctcg ggtctccatg aggtggtgtc cccgctcggt gacgaagagg ctgtccgtgt 5831
ctccgtagac cgacttgagg ggtcttttct ccaagggggt ccctcggtct tcctcgtaga 5891
ggaactcgga ccactctgag acgaaggccc gcgtccaggc caggacgaag gaggctatgt 5951
gggaggggta gcggtcgttg tccactaggg ggtccacctt ctccaaggtg tgaagacaca 6011
tgtcgccttc ctcggcgtcc aggaaggtga ttggcttgta ggtgtaggcc acgtgaccgg 6071
gggttcctga cgggggggta taaaaggggg tgggggcgcg ctcgtcgtca ctctcttccg 6131
catcgctgtc tgcgagggcc agctgctggg gtgagtattc cctctcgaag gcgggcatga 6191
cctccgcgct gaggttgtca gtttccaaaa acgaggagga tttgatgttc acctgtcccg 6251
aggtgatacc tttgagggta cccgcgtcca tctggtcaga aaacacgatc tttttattgt 6311
ccagcttggt ggcgaacgac ccgtagaggg cgttggagag cagcttggcg atggagcgca 6371
gggtctggtt cttgtccctg tcggcgcgct ccttggccgc gatgttgagc tgcacgtact 6431
cgcgcgcgac gcagcgccac tcggggaaga cggtggtgcg ctcgtcgggc accaggcgca 6491
cgcgccagcc gcggttgtgc agggtgacca ggtccacgct ggtggcgacc tcgccgcgca 6551
ggcgctcgtt ggtccagcag agacggccgc ccttgcgcga gcagaagggg ggcagggggt 6611
cgagctgggt ctcgtccggg gggtccgcgt ccacggtgaa gaccccgggg cgcaggcgcg 6671
cgtcgaagta gtctatcttg caaccttgca tgtccagcgc ctgctgccag tcgcgggcgg 6731
cgagcgcgcg ctcgtagggg ttgagcggcg ggccccaggg catggggtgg gtgagcgcgg 6791
aggcgtacat gccgcagatg tcatagacgt agaggggctc ccgcaggacc ccgatgtagg 6851
tggggtagca gcggccgccg cggatgctgg cgcgcacgta gtcatacagc tcgtgcgagg 6911
gggcgaggag gtcggggccc aggttggtgc gggcggggcg ctccgcgcgg aagacgatct 6971
gcctgaagat ggcatgcgag ttggaagaga tggtggggcg ctggaagacg ttgaagctgg 7031
cgtcctgcag gccgacggcg tcgcgcacga aggaggcgta ggagtcgcgc agcttgtgta 7091
ccagctcggc ggtgacctgc acgtcgagcg cgcagtagtc gagggtctcg cggatgatgt 7151
catacttagc ctgccccttc tttttccaca gctcgcggtt gaggacaaac tcttcgcggt 7211
ctttccagta ctcttggatc gggaaaccgt ccggttccga acggtaagag cctagcatgt 7271
agaactggtt gacggcctgg taggcgcagc agcccttctc cacggggagg gcgtaggcct 7331
gcgcggcctt gcggagcgag gtgtgggtca gggcgaaggt gtccctgacc atgactttga 7391
ggtactggtg cttgaagtcg gagtcgtcgc agccgccccg ctcccagagc gagaagtcgg 7451
tgcgcttctt ggagcggggg ttgggcagag cgaaggtgac atcgttgaag aggattttgc 7511
ccgcgcgggg catgaagttg cgggtgatgc ggaagggccc cggcacttca gagcggttgt 7571
tgatgacctg ggcggcgagc acgatctcgt cgaagccgtt gatgttgtgg cccacgatgt 7631
agagttccag gaagcggggc cggcccttta cggtgggcag cttctttagc tcttcgtagg 7691
tgagctcctc gggcgaggcg aggccgtgct cggccagggc ccagtccgcg aggtgcgggt 7751
tgtctctgag gaaggactcc cagaggtcgc gggccaggag ggtctgcagg cggtctctga 7811
aggtcctgaa ctggcggccc acggccattt tttcgggggt gatgcagtag aaggtgaggg 7871
ggtcttgctg ccagcggtcc cagtcgagct gcagggcgag gtcgcgcgcg gcggtgacca 7931
ggcgctcgtc gcccccgaat ttcatgacca gcatgaaggg cacgagctgc tttccgaagg 7991
cccccatcca agtgtaggtc tctacatcgt aggtgacaaa gaggcgctcc gtgcgaggat 8051
gcgagccgat cgggaagaac tggatctccc gccaccagtt ggaggagtgg ctgttgatgt 8111
ggtggaagta gaagtcccgt cgccgggccg agcactcgtg ctggcttttg taaaagcgag 8171
cgcagtactg gcagcgctgc acgggctgta cctcctgcac gagatgcacc tttcgcccgc 8231
gcacgaggaa gccgaggggg aatctgagcc ccccgcctgg ctcgcggcat ggctggtgct 8291
cttctacttt ggatgcgtgt ccgtctctgt ctggctcctc gaggggtgtt acggtggagc 8351
ggaccaccac gccgcgcgag ccgcaggtcc agatatcggc gcgcggcggt cggagtttga 8411
tgacgacatc gcgcagctgg gagctgtcca tggtctggag ctcccgcggc ggcggcaggt 8471
cagccgggag ttcttgcagg ttcacctcgc agagtcgggc cagggcgcgg ggcaggtcta 8531
ggtggtactt gatctctagg ggcgtgttgg tggcggcgtc gatggcttgc aggagcccgc 8591
agccccgggg cgcgacgacg gtgccccgcg gggtggtggt ggtggcggtg ctgctcagaa 8651
gcggtgccgc gggcgggccc ccggaggtag ggggggctcc ggtcccgcgg gcaggggcgg 8711
cagcggcacg tcggcgtgga gcgcgggcag gagttggtgc tgtgcccgga ggttgctggc 8771
gaaggcgacg acgcggcggt tgatctcctg gatctggcgc ctctgcgtga agacgacggg 8831
cccggtgagc ttgaacctga aagagagttc gacagaatca atctcggtgt cattgaccgc 8891
ggcctggcgc aggatctcct gcacgtctcc cgagttgtct tggtaggcga tctcagccat 8951
gaactgctcg atctcttcct cctggaggtc tccgcgtccg gcgcgttcca cggtggccgc 9011
caggtcgttg gagatgcgcc ccatgagctg cgagaaggcg ttgagtccgc cctcgttcca 9071
gactcggctg tagaccacgc ccccctggtc gtcgcgggcg cgcatgacca cctgcgcgag 9131
gttgagctcc acgtgccgcg cgaagacggc gtagttgcgc agacgctgga agaggtagtt 9191
gagggtggtg gcggtgtgct cggccacgaa gaagttcatg acccagcggc gcaacgtgga 9251
ttcgttgatg tcccccaagg cctccagccg ttccatggcc tcgtagaagt ccacggcgaa 9311
gttgaaaaac tgggagttgc gcgccgacac ggtcaactcc tcctccagaa gacggatgag 9371
ctcggcgacg gtgtcgcgca cctcgcgctc gaaggctatg gggatctctt cctccgctag 9431
catcaccacc tcctcctctt cctcctcttc tggcacttcc atgatggctt cctcctcttc 9491
ggggggtggc ggcggcggcg gtgggggagg gggcgctctg cgccggcggc ggcgcaccgg 9551
aaggcggtcc acgaagcgcg cgatcatctc cccgcggcgg cggcgcatgg tctcggtgac 9611
ggcgcggccg ttctcccggg ggcgcagttg gaagacgccg ccggacatct ggtgctgggg 9671
cgggtggccg tgaggcagcg agacggcgct gacgatgcat ctcaacaatt gctgcgtagg 9731
tacgccgccg agggacctga gggagtccat atccaccgga tccgaaaacc tttcgaggaa 9791
ggcgtctaac cagtcgcagt cgcaaggtag gctgagcacc gtggcgggcg gcggggggtg 9851
gggggagtgt ctggcggagg tgctgctgat gatgtaattg aagtaggcgg acttgacacg 9911
gcggatggtc gacaggagca ccatgtcctt gggtccggcc tgctggatgc ggaggcggtc 9971
ggctatgccc caggcttcgt tctggcatcg gcgcaggtcc ttgtagtagt cttgcatgag 10031
cctttccacc ggcacctctt ctccttcctc ttctgcttct tccatgtctg cttcggccct 10091
ggggcggtgc cgcgcccccc tgccccccat gcgcgtgacc ccgaaccccc tgagcggttg 10151
gagcagggcc aggtcggcga cgacgcgctc ggccaggatg gcctgctgca cctgcgtgag 10211
ggtggtttgg aagtcatcca agtccacgaa gcggtggtag gcgcccgtgt tgatggtgta 10271
ggtgcagttg gccatgacgg accagttgac ggtctggtgg cccggttgcg acatctcggt 10331
gtacctgagt cgcgagtagg cgcgggagtc gaagacgtag tcgttgcaag tccgcaccag 10391
gtactggtag cccaccagga agtgcggcgg cggctggcgg tagaggggcc agcgcagggt 10451
ggcgggggct ccgggggcca ggtcttccag catgaggcgg tggtaggcgt agatgtacct 10511
ggacatccag gtgatacccg cggcggtggt ggaggcgcgc ggaaagtcgc gcacccggtt 10571
ccagatgttg cgcaggggca gaaagtgctc catggtaggc gtgctctgtc cagtcagacg 10631
cgcgcagtcg ttgatactct agaccaggga aaacgaaagc cggtcagcgg gcactcttcc 10691
gtggtctggt gaatagatcg caagggtatc atggcggagg gcctcggttc gagccccggg 10751
tccgggccgg acggtccgcc atgatccacg cggttaccgc ccgcgtgtcg aacccaggtg 10811
tgcgacgtca gacaacggtg gagtgttcct tttggcgttt ttctggccgg gcgccggcgc 10871
cgcgtaagag actaagccgc gaaagcgaaa gcagtaagtg gctcgctccc cgtagccgga 10931
gggatccttg ctaagggttg cgttgcggcg aaccccggtt cgaatcccgt actcgggccg 10991
gccggacccg cggctaaggt gttggattgg cctccccctc gtataaagac cccgcttgcg 11051
gattgactcc ggacacgggg acgagcccct tttatttttg ctttccccag atg cat 11107
Met His
ccg gtg ctg cgg cag atg cgc ccc ccg ccc cag cag cag caa caa cac 11155
Pro Val Leu Arg Gln Met Arg Pro Pro Pro Gln Gln Gln Gln Gln His
370 375 380 385
cag caa gag cgg cag caa cag cag cgg gag tca tgc agg gcc ccc tca 11203
Gln Gln Glu Arg Gln Gln Gln Gln Arg Glu Ser Cys Arg Ala Pro Ser
390 395 400
ccc acc ctc ggc ggg ccg gcc acc tcg gcg tcc gcg gcc gtg tct ggc 11251
Pro Thr Leu Gly Gly Pro Ala Thr Ser Ala Ser Ala Ala Val Ser Gly
405 410 415
gcc tgc ggc ggc ggc ggg ggg ccg gct gac gac ccc gag gag ccc ccg 11299
Ala Cys Gly Gly Gly Gly Gly Pro Ala Asp Asp Pro Glu Glu Pro Pro
420 425 430
cgg cgc agg gcc aga cac tac ctg gac ctg gag gag ggc gag ggc ctg 11347
Arg Arg Arg Ala Arg His Tyr Leu Asp Leu Glu Glu Gly Glu Gly Leu
435 440 445
gcg cgg ctg ggg gcg ccg tct ccc gag cgc cac ccg cgg gtg cag ctg 11395
Ala Arg Leu Gly Ala Pro Ser Pro Glu Arg His Pro Arg Val Gln Leu
450 455 460 465
aag cgc gac tcg cgc gag gcg tac gtg cct cgg cag aac ctg ttc agg 11443
Lys Arg Asp Ser Arg Glu Ala Tyr Val Pro Arg Gln Asn Leu Phe Arg
470 475 480
gac cgc gcg ggc gag gag ccc gag gag atg cgg gac agg agg ttc agc 11491
Asp Arg Ala Gly Glu Glu Pro Glu Glu Met Arg Asp Arg Arg Phe Ser
485 490 495
gca ggg cgg gag ctg cgg cag ggg ctg aac cgc gag cgg ctg ctg cgc 11539
Ala Gly Arg Glu Leu Arg Gln Gly Leu Asn Arg Glu Arg Leu Leu Arg
500 505 510
gag gag gac ttt gag ccc gac gcg cgg acg ggg atc agc ccc gcg cgc 11587
Glu Glu Asp Phe Glu Pro Asp Ala Arg Thr Gly Ile Ser Pro Ala Arg
515 520 525
gcg cac gtg gcg gcc gcc gac ctg gtg acg gcg tac gag cag acg gtg 11635
Ala His Val Ala Ala Ala Asp Leu Val Thr Ala Tyr Glu Gln Thr Val
530 535 540 545
aac cag gag atc aac ttc caa aag agt ttc aac aac cac gtg cgc acg 11683
Asn Gln Glu Ile Asn Phe Gln Lys Ser Phe Asn Asn His Val Arg Thr
550 555 560
ctg gtg gcg cgc gag gag gtg acc atc ggg ctg atg cac ctg tgg gac 11731
Leu Val Ala Arg Glu Glu Val Thr Ile Gly Leu Met His Leu Trp Asp
565 570 575
ttt gta agc gcg ctg gtg cag aac ccc aac agc aag cct ctg acg gcg 11779
Phe Val Ser Ala Leu Val Gln Asn Pro Asn Ser Lys Pro Leu Thr Ala
580 585 590
cag ctg ttc ctg ata gtg cag cac agc agg gac aac gag gcg ttt agg 11827
Gln Leu Phe Leu Ile Val Gln His Ser Arg Asp Asn Glu Ala Phe Arg
595 600 605
gac gcg ctg ctg aac atc acc gag ccc gag ggt cgg tgg ctg ctg gac 11875
Asp Ala Leu Leu Asn Ile Thr Glu Pro Glu Gly Arg Trp Leu Leu Asp
610 615 620 625
ctg att aac atc ctg cag agc ata gtg gtg cag gag cgc agc ctg agc 11923
Leu Ile Asn Ile Leu Gln Ser Ile Val Val Gln Glu Arg Ser Leu Ser
630 635 640
ctg gcc gac aag gtg gcg gcc atc aac tac tcg atg ctg agc ctg ggc 11971
Leu Ala Asp Lys Val Ala Ala Ile Asn Tyr Ser Met Leu Ser Leu Gly
645 650 655
aag ttt tac gcg cgc aag atc tac cag acg ccg tac gtg ccc ata gac 12019
Lys Phe Tyr Ala Arg Lys Ile Tyr Gln Thr Pro Tyr Val Pro Ile Asp
660 665 670
aag gag gtg aag atc gac ggt ttt tac atg cgc atg gcg ctg aag gtg 12067
Lys Glu Val Lys Ile Asp Gly Phe Tyr Met Arg Met Ala Leu Lys Val
675 680 685
ctc acc ctg agc gac gac ctg ggc gtg tac cgc aac gag cgc atc cac 12115
Leu Thr Leu Ser Asp Asp Leu Gly Val Tyr Arg Asn Glu Arg Ile His
690 695 700 705
aag gcc gtg agc gtg agc cgg cgg cgc gag ctg agc gac cgc gag ctg 12163
Lys Ala Val Ser Val Ser Arg Arg Arg Glu Leu Ser Asp Arg Glu Leu
710 715 720
atg cac agc ctg cag cgg gcg ctg gcg ggc gcc ggc agc ggc gac agg 12211
Met His Ser Leu Gln Arg Ala Leu Ala Gly Ala Gly Ser Gly Asp Arg
725 730 735
gag gtg gag tcc tac ttt gat gcg ggg gcg gac ctg cgc tgg gcg ccc 12259
Glu Val Glu Ser Tyr Phe Asp Ala Gly Ala Asp Leu Arg Trp Ala Pro
740 745 750
agc cgg cgg gcc ctg gag gcc gcg ggg gtc cgc gag gac tat gac gag 12307
Ser Arg Arg Ala Leu Glu Ala Ala Gly Val Arg Glu Asp Tyr Asp Glu
755 760 765
gac ggc gag gag gat gag gag tac gag cta gag gag ggc gag tac ctg 12355
Asp Gly Glu Glu Asp Glu Glu Tyr Glu Leu Glu Glu Gly Glu Tyr Leu
770 775 780 785
gac taaaccgcgg gtggtgtttc cggtag atg caa gac ccg aac gtg gtg gac 12408
Asp Met Gln Asp Pro Asn Val Val Asp
790
ccg gcg ctg cgg gcg gct ctg cag agc cag ccg tcc ggc ctt aac tcc 12456
Pro Ala Leu Arg Ala Ala Leu Gln Ser Gln Pro Ser Gly Leu Asn Ser
795 800 805 810
tca gac gac tgg cga cag gtc atg gac cgc atc atg tcg ctg acg gcg 12504
Ser Asp Asp Trp Arg Gln Val Met Asp Arg Ile Met Ser Leu Thr Ala
815 820 825
cgt aac ccg gac gcg ttc cgg cag cag ccg cag gcc aac agg ctc tcc 12552
Arg Asn Pro Asp Ala Phe Arg Gln Gln Pro Gln Ala Asn Arg Leu Ser
830 835 840
gcc atc ctg gag gcg gtg gtg cct gcg cgc tcg aac ccc acg cac gag 12600
Ala Ile Leu Glu Ala Val Val Pro Ala Arg Ser Asn Pro Thr His Glu
845 850 855
aag gtg ctg gcc ata gtg aac gcg ctg gcc gag aac agg gcc atc cgc 12648
Lys Val Leu Ala Ile Val Asn Ala Leu Ala Glu Asn Arg Ala Ile Arg
860 865 870
ccg gac gag gcc ggg ctg gtg tac gac gcg ctg ctg cag cgc gtg gcc 12696
Pro Asp Glu Ala Gly Leu Val Tyr Asp Ala Leu Leu Gln Arg Val Ala
875 880 885 890
cgc tac aac agc ggc aac gtg cag acc aac ctg gac cgg ctg gtg ggg 12744
Arg Tyr Asn Ser Gly Asn Val Gln Thr Asn Leu Asp Arg Leu Val Gly
895 900 905
gac gtg cgc gag gcg gtg gcg cag cgc gag cgc gcg gat cgg cag ggc 12792
Asp Val Arg Glu Ala Val Ala Gln Arg Glu Arg Ala Asp Arg Gln Gly
910 915 920
aac ctg ggc tcc atg gtg gcg ctg aat gcc ttc ctg agc acg cag ccg 12840
Asn Leu Gly Ser Met Val Ala Leu Asn Ala Phe Leu Ser Thr Gln Pro
925 930 935
gcc aac gtg ccg cgg ggg cag gaa gac tac acc aac ttt gtg agc gcg 12888
Ala Asn Val Pro Arg Gly Gln Glu Asp Tyr Thr Asn Phe Val Ser Ala
940 945 950
ctg cgg ctg atg gtg acc gag acc ccc cag agc gag gtg tac cag tcg 12936
Leu Arg Leu Met Val Thr Glu Thr Pro Gln Ser Glu Val Tyr Gln Ser
955 960 965 970
ggc ccg gac tac ttc ttc cag acc agc aga cag ggc ctg cag acg gtg 12984
Gly Pro Asp Tyr Phe Phe Gln Thr Ser Arg Gln Gly Leu Gln Thr Val
975 980 985
aac ctg agc cag gct ttc aag aac ctg cgg ggg ctg tgg ggc gtg aag 13032
Asn Leu Ser Gln Ala Phe Lys Asn Leu Arg Gly Leu Trp Gly Val Lys
990 995 1000
gcg ccc acc ggc gac cgg gcg acg gtg tcc agc ctg ctg acg ccc 13077
Ala Pro Thr Gly Asp Arg Ala Thr Val Ser Ser Leu Leu Thr Pro
1005 1010 1015
aac tcg cgc ctg ctg ctg ctg ctg atc gcg ccg ttc acg gac agc 13122
Asn Ser Arg Leu Leu Leu Leu Leu Ile Ala Pro Phe Thr Asp Ser
1020 1025 1030
ggc agc gtg tcc cgg gac acc tac ctg ggg cac ctg ctg acc ctg 13167
Gly Ser Val Ser Arg Asp Thr Tyr Leu Gly His Leu Leu Thr Leu
1035 1040 1045
tac cgc gag gcc atc ggg cag gcg cag gtg gac gag cac acc ttc 13212
Tyr Arg Glu Ala Ile Gly Gln Ala Gln Val Asp Glu His Thr Phe
1050 1055 1060
cag gag atc acc agc gtg agc cgc gcg ctg ggg cag gag gac acg 13257
Gln Glu Ile Thr Ser Val Ser Arg Ala Leu Gly Gln Glu Asp Thr
1065 1070 1075
agc agc ctg gag gcg act ctg aac tac ctg ctg acc aac cgg cgg 13302
Ser Ser Leu Glu Ala Thr Leu Asn Tyr Leu Leu Thr Asn Arg Arg
1080 1085 1090
cag aag att ccc tcg ctg cac agc ctg acc tcc gag gag gag cgc 13347
Gln Lys Ile Pro Ser Leu His Ser Leu Thr Ser Glu Glu Glu Arg
1095 1100 1105
atc ttg cgc tac gtg cag cag agc gtg agc ctg aac ctg atg cgc 13392
Ile Leu Arg Tyr Val Gln Gln Ser Val Ser Leu Asn Leu Met Arg
1110 1115 1120
gac ggg gtg acg ccc agc gtg gcg ctg gac atg acc gcg cgc aac 13437
Asp Gly Val Thr Pro Ser Val Ala Leu Asp Met Thr Ala Arg Asn
1125 1130 1135
atg gaa ccg ggc atg tac gcc gcg cac cgg cct tac atc aac cgc 13482
Met Glu Pro Gly Met Tyr Ala Ala His Arg Pro Tyr Ile Asn Arg
1140 1145 1150
ctg atg gac tac ctg cat cgc gcg gcg gcc gtg aac ccc gag tac 13527
Leu Met Asp Tyr Leu His Arg Ala Ala Ala Val Asn Pro Glu Tyr
1155 1160 1165
ttt acc aac gct atc ctg aac ccg cac tgg ctc ccg ccg ccc ggg 13572
Phe Thr Asn Ala Ile Leu Asn Pro His Trp Leu Pro Pro Pro Gly
1170 1175 1180
ttc tac agc ggg ggc ttc gag gtc ccg gag gcc aac gat ggc ttc 13617
Phe Tyr Ser Gly Gly Phe Glu Val Pro Glu Ala Asn Asp Gly Phe
1185 1190 1195
ctg tgg gac gac atg gac gac agc gtg ttc tcc ccg cgg ccg cag 13662
Leu Trp Asp Asp Met Asp Asp Ser Val Phe Ser Pro Arg Pro Gln
1200 1205 1210
gcg ctg gcg gaa gcg tcc ctg ctg cgc ccc aag aag gag gag gag 13707
Ala Leu Ala Glu Ala Ser Leu Leu Arg Pro Lys Lys Glu Glu Glu
1215 1220 1225
gcg agt cgc cgc cgc cgc ggc agc agc ggc gtg gct tct ctg tcc 13752
Ala Ser Arg Arg Arg Arg Gly Ser Ser Gly Val Ala Ser Leu Ser
1230 1235 1240
gag ctg ggg gcg gca gcc gcc gcg cgc ccc ggg tcc ctg ggc ggc 13797
Glu Leu Gly Ala Ala Ala Ala Ala Arg Pro Gly Ser Leu Gly Gly
1245 1250 1255
agc ccc ttt ccg agc ctg gtg ggg tct ctg cac agc gag cgc acc 13842
Ser Pro Phe Pro Ser Leu Val Gly Ser Leu His Ser Glu Arg Thr
1260 1265 1270
acc cgc ccc cgg ctg ctg ggc gag gac gag tac ctg aat aac tcc 13887
Thr Arg Pro Arg Leu Leu Gly Glu Asp Glu Tyr Leu Asn Asn Ser
1275 1280 1285
ctg ctg cag ccg gtg cgg gag aaa aac ctg cct ccc gcc ttc ccc 13932
Leu Leu Gln Pro Val Arg Glu Lys Asn Leu Pro Pro Ala Phe Pro
1290 1295 1300
aac aac ggg ata gag agc ctg gtg gac aag atg agc aga tgg aag 13977
Asn Asn Gly Ile Glu Ser Leu Val Asp Lys Met Ser Arg Trp Lys
1305 1310 1315
acc tat gcg cag gag cac agg gac gcg ccc gcg ctc cgg ccg ccc 14022
Thr Tyr Ala Gln Glu His Arg Asp Ala Pro Ala Leu Arg Pro Pro
1320 1325 1330
acg cgg cgc cag cgc cac gac cgg cag cgg ggg ctg gtg tgg gat 14067
Thr Arg Arg Gln Arg His Asp Arg Gln Arg Gly Leu Val Trp Asp
1335 1340 1345
gac gag gac tcc gcg gac gat agc agc gtg ctg gac ctg gga ggg 14112
Asp Glu Asp Ser Ala Asp Asp Ser Ser Val Leu Asp Leu Gly Gly
1350 1355 1360
agc ggc aac ccg ttc gcg cac ctg cgc ccc cgc ctg ggg agg atg 14157
Ser Gly Asn Pro Phe Ala His Leu Arg Pro Arg Leu Gly Arg Met
1365 1370 1375
ttt taaaaaaaaa aaaaagcaag aagc atg atg caa aaa tta aat aaa act 14208
Phe Met Met Gln Lys Leu Asn Lys Thr
1380 1385
cac caa ggc cat ggc gac cga gcg ttg gtt tct tgt gtt ccc ttc 14253
His Gln Gly His Gly Asp Arg Ala Leu Val Ser Cys Val Pro Phe
1390 1395 1400
agt atg cgg cgc gcg gcg atg tac cag gag gga cct cct ccc tct 14298
Ser Met Arg Arg Ala Ala Met Tyr Gln Glu Gly Pro Pro Pro Ser
1405 1410 1415
tac gag agc gtg gtg ggc gcg gcg gcg gcg gcg ccc tct tct ccc 14343
Tyr Glu Ser Val Val Gly Ala Ala Ala Ala Ala Pro Ser Ser Pro
1420 1425 1430
ttt gcg tcg cag ctg ctg gag ccg ccg tac gtg cct ccg cgc tac 14388
Phe Ala Ser Gln Leu Leu Glu Pro Pro Tyr Val Pro Pro Arg Tyr
1435 1440 1445
ctg cgg cct acg ggg ggg aga aac agc atc cgt tac tcg gag ctg 14433
Leu Arg Pro Thr Gly Gly Arg Asn Ser Ile Arg Tyr Ser Glu Leu
1450 1455 1460
gcg ccc ctg ttc gac acc acc cgg gtg tac ctg gtg gac aac aag 14478
Ala Pro Leu Phe Asp Thr Thr Arg Val Tyr Leu Val Asp Asn Lys
1465 1470 1475
tcg gcg gac gtg gcc tcc ctg aac tac cag aac gac cac agc aat 14523
Ser Ala Asp Val Ala Ser Leu Asn Tyr Gln Asn Asp His Ser Asn
1480 1485 1490
ttt ttg acc acg gtc atc cag aac aat gac tac agc ccg agc gag 14568
Phe Leu Thr Thr Val Ile Gln Asn Asn Asp Tyr Ser Pro Ser Glu
1495 1500 1505
gcc agc acc cag acc atc aat ctg gat gac cgg tcg cac tgg ggc 14613
Ala Ser Thr Gln Thr Ile Asn Leu Asp Asp Arg Ser His Trp Gly
1510 1515 1520
ggc gac ctg aaa acc atc ctg cac acc aac atg ccc aac gtg aac 14658
Gly Asp Leu Lys Thr Ile Leu His Thr Asn Met Pro Asn Val Asn
1525 1530 1535
gag ttc atg ttc acc aat aag ttc aag gcg cgg gtg atg gtg tcg 14703
Glu Phe Met Phe Thr Asn Lys Phe Lys Ala Arg Val Met Val Ser
1540 1545 1550
cgc tcg cac acc aag gaa gac cgg gtg gag ctg aag tac gag tgg 14748
Arg Ser His Thr Lys Glu Asp Arg Val Glu Leu Lys Tyr Glu Trp
1555 1560 1565
gtg gag ttc gag ctg cca gag ggc aac tac tcc gag acc atg acc 14793
Val Glu Phe Glu Leu Pro Glu Gly Asn Tyr Ser Glu Thr Met Thr
1570 1575 1580
att gac ctg atg aac aac gcg atc gtg gag cac tat ctg aaa gtg 14838
Ile Asp Leu Met Asn Asn Ala Ile Val Glu His Tyr Leu Lys Val
1585 1590 1595
ggc agg cag aac ggg gtc ctg gag agc gac atc ggg gtc aag ttc 14883
Gly Arg Gln Asn Gly Val Leu Glu Ser Asp Ile Gly Val Lys Phe
1600 1605 1610
gac acc agg aac ttc cgc ctg ggg ctg gac ccc gtg acc ggg ctg 14928
Asp Thr Arg Asn Phe Arg Leu Gly Leu Asp Pro Val Thr Gly Leu
1615 1620 1625
gtt atg ccc ggg gtg tac acc aac gag gcc ttc cat ccc gac atc 14973
Val Met Pro Gly Val Tyr Thr Asn Glu Ala Phe His Pro Asp Ile
1630 1635 1640
atc ctg ctg ccc ggc tgc ggg gtg gac ttc act tac agc cgc ctg 15018
Ile Leu Leu Pro Gly Cys Gly Val Asp Phe Thr Tyr Ser Arg Leu
1645 1650 1655
agc aac ctc ctg ggc atc cgc aag cgg cag ccc ttc cag gag ggc 15063
Ser Asn Leu Leu Gly Ile Arg Lys Arg Gln Pro Phe Gln Glu Gly
1660 1665 1670
ttc agg atc acc tac gag gac ctg gag ggg ggc aac atc ccc gcg 15108
Phe Arg Ile Thr Tyr Glu Asp Leu Glu Gly Gly Asn Ile Pro Ala
1675 1680 1685
cta ctc gat gtg gag gcc tac cag gat agc ttg aag gaa aat gag 15153
Leu Leu Asp Val Glu Ala Tyr Gln Asp Ser Leu Lys Glu Asn Glu
1690 1695 1700
gcg gga cag gag gat acc gcc ccc gcc gcc tcc gcc gcc gcc gag 15198
Ala Gly Gln Glu Asp Thr Ala Pro Ala Ala Ser Ala Ala Ala Glu
1705 1710 1715
cag ggc gag gat gct gct gac acc gcg gcc gcg gac ggg gcg gaa 15243
Gln Gly Glu Asp Ala Ala Asp Thr Ala Ala Ala Asp Gly Ala Glu
1720 1725 1730
gcc gat ccc gct atg gtg gtg gag gct gcc gag cag gag gag gac 15288
Ala Asp Pro Ala Met Val Val Glu Ala Ala Glu Gln Glu Glu Asp
1735 1740 1745
atg aat gac agt gcg gtg cgc gga gac acc ttc gtc acc cgg ggg 15333
Met Asn Asp Ser Ala Val Arg Gly Asp Thr Phe Val Thr Arg Gly
1750 1755 1760
gag gaa aag caa gcg gag gcc gag gcc gcg gcc gag gaa aag caa 15378
Glu Glu Lys Gln Ala Glu Ala Glu Ala Ala Ala Glu Glu Lys Gln
1765 1770 1775
ctg gcg gca gca gcg gcg gcg gcg gcg ttg gcc gcg gcg gag gct 15423
Leu Ala Ala Ala Ala Ala Ala Ala Ala Leu Ala Ala Ala Glu Ala
1780 1785 1790
gag tct gag ggg acc aag cct gcc aag gag ccc gtg att aag ccc 15468
Glu Ser Glu Gly Thr Lys Pro Ala Lys Glu Pro Val Ile Lys Pro
1795 1800 1805
ctg acc gaa gat agc aag aag cgc agt tac aac ctg ctc aag gac 15513
Leu Thr Glu Asp Ser Lys Lys Arg Ser Tyr Asn Leu Leu Lys Asp
1810 1815 1820
agc acc aac acc gcg tac cgc agc tgg tac ctg gcc tac aac tac 15558
Ser Thr Asn Thr Ala Tyr Arg Ser Trp Tyr Leu Ala Tyr Asn Tyr
1825 1830 1835
ggc gac ccg tcg acg ggg gtg cgc tcc tgg acc ctg ctg tgc acg 15603
Gly Asp Pro Ser Thr Gly Val Arg Ser Trp Thr Leu Leu Cys Thr
1840 1845 1850
ccg gac gtg acc tgc ggc tcg gag cag gtg tac tgg tcg ctg ccc 15648
Pro Asp Val Thr Cys Gly Ser Glu Gln Val Tyr Trp Ser Leu Pro
1855 1860 1865
gac atg atg caa gac ccc gtg acc ttc cgc tcc acg cgg cag gtc 15693
Asp Met Met Gln Asp Pro Val Thr Phe Arg Ser Thr Arg Gln Val
1870 1875 1880
agc aac ttc ccg gtg gtg ggc gcc gag ctg ctg ccc gtg cac tcc 15738
Ser Asn Phe Pro Val Val Gly Ala Glu Leu Leu Pro Val His Ser
1885 1890 1895
aag agc ttc tac aac gac cag gcc gtc tac tcc cag ctc atc cgc 15783
Lys Ser Phe Tyr Asn Asp Gln Ala Val Tyr Ser Gln Leu Ile Arg
1900 1905 1910
cag ttc acc tct ctg acc cac gtg ttc aat cgc ttt cct gag aac 15828
Gln Phe Thr Ser Leu Thr His Val Phe Asn Arg Phe Pro Glu Asn
1915 1920 1925
cag att ctg gcg cgc ccg ccc gcc ccc acc atc acc acc gtc agt 15873
Gln Ile Leu Ala Arg Pro Pro Ala Pro Thr Ile Thr Thr Val Ser
1930 1935 1940
gaa aac gtt cct gct ctc aca gat cac ggg acg cta ccg ctg cgc 15918
Glu Asn Val Pro Ala Leu Thr Asp His Gly Thr Leu Pro Leu Arg
1945 1950 1955
aac agc atc gga gga gtc cag cga gtg acc gtt act gac gcc aga 15963
Asn Ser Ile Gly Gly Val Gln Arg Val Thr Val Thr Asp Ala Arg
1960 1965 1970
cgc cgc acc tgc ccc tac gtt tac aag gcc ttg ggc ata gtc tcg 16008
Arg Arg Thr Cys Pro Tyr Val Tyr Lys Ala Leu Gly Ile Val Ser
1975 1980 1985
ccg cgc gtc ctt tcc agc cgc act ttt tgagcaacac caccatc atg tcc 16058
Pro Arg Val Leu Ser Ser Arg Thr Phe Met Ser
1990 1995
atc ctg atc tca ccc agc aat aac tcc ggc tgg gga ctg ctg cgc 16103
Ile Leu Ile Ser Pro Ser Asn Asn Ser Gly Trp Gly Leu Leu Arg
2000 2005 2010
gcg ccc agc aag atg ttc gga ggg gcg agg aag cgt tcc gag cag 16148
Ala Pro Ser Lys Met Phe Gly Gly Ala Arg Lys Arg Ser Glu Gln
2015 2020 2025
cac ccc gtg cgc gtg cgc ggg cac ttc cgc gcc ccc tgg gga gcg 16193
His Pro Val Arg Val Arg Gly His Phe Arg Ala Pro Trp Gly Ala
2030 2035 2040
cac aaa cgc ggc cgc gcg ggg cgc acc acc gtg gac gac gcc atc 16238
His Lys Arg Gly Arg Ala Gly Arg Thr Thr Val Asp Asp Ala Ile
2045 2050 2055
gac tcg gtg gtg gag cag gcg cgc aac tac agg ccc gcg gtc tct 16283
Asp Ser Val Val Glu Gln Ala Arg Asn Tyr Arg Pro Ala Val Ser
2060 2065 2070
acc gtg gac gcg gcc atc cag acc gtg gtg cgg ggc gcg cgg cgg 16328
Thr Val Asp Ala Ala Ile Gln Thr Val Val Arg Gly Ala Arg Arg
2075 2080 2085
tac gcc aag ctg aag agc cgc cgg aag cgc gtg gcc cgc cgc cac 16373
Tyr Ala Lys Leu Lys Ser Arg Arg Lys Arg Val Ala Arg Arg His
2090 2095 2100
cgc cgc cga ccc ggg gcc gcc gcc aaa cgc gcc gcc gcg gcc ctg 16418
Arg Arg Arg Pro Gly Ala Ala Ala Lys Arg Ala Ala Ala Ala Leu
2105 2110 2115
ctt cgc cgg gcc aag cgc acg ggc cgc cgc gcc gcc atg agg gcc 16463
Leu Arg Arg Ala Lys Arg Thr Gly Arg Arg Ala Ala Met Arg Ala
2120 2125 2130
gcg cgc cgc ttg gcc gcc ggc atc acc gcc gcc acc atg gcc ccc 16508
Ala Arg Arg Leu Ala Ala Gly Ile Thr Ala Ala Thr Met Ala Pro
2135 2140 2145
cgt acc cga aga cgc gcg gcc gcc gcc gcc gcc gcc gcc atc agt 16553
Arg Thr Arg Arg Arg Ala Ala Ala Ala Ala Ala Ala Ala Ile Ser
2150 2155 2160
gac atg gcc agc agg cgc cgg ggc aac gtg tac tgg gtg cgc gac 16598
Asp Met Ala Ser Arg Arg Arg Gly Asn Val Tyr Trp Val Arg Asp
2165 2170 2175
tcg gtg acc ggc acg cgc gtg ccc gtg cgc ttc cgc ccc ccg cgg 16643
Ser Val Thr Gly Thr Arg Val Pro Val Arg Phe Arg Pro Pro Arg
2180 2185 2190
act tgagatgatg tgaaaaaaca acactgagtc tcctgctgtt gtgtgtatcc 16696
Thr
cagcggcggc ggcgcgcgca gcgtc atg tcc aag cgc aaa atc aaa gaa gag 16748
Met Ser Lys Arg Lys Ile Lys Glu Glu
2195 2200
atg ctc cag gtc gtc gcg ccg gag atc tat ggg ccc ccg aag aag 16793
Met Leu Gln Val Val Ala Pro Glu Ile Tyr Gly Pro Pro Lys Lys
2205 2210 2215
gaa gag cag gat tcg aag ccc cgc aag ata aag cgg gtc aaa aag 16838
Glu Glu Gln Asp Ser Lys Pro Arg Lys Ile Lys Arg Val Lys Lys
2220 2225 2230
aaa aag aaa gat gat gac gat gcc gat ggg gag gtg gag ttc ctg 16883
Lys Lys Lys Asp Asp Asp Asp Ala Asp Gly Glu Val Glu Phe Leu
2235 2240 2245
cgc gcc acg gcg ccc agg cgc ccg gtg cag tgg aag ggc cgg cgc 16928
Arg Ala Thr Ala Pro Arg Arg Pro Val Gln Trp Lys Gly Arg Arg
2250 2255 2260
gta aag cgc gtc ctg cgc ccc ggc acc gcg gtg gtc ttc acg ccc 16973
Val Lys Arg Val Leu Arg Pro Gly Thr Ala Val Val Phe Thr Pro
2265 2270 2275
ggc gag cgc tcc acc cgg act ttc aag cgc gtc tat gac gag gtg 17018
Gly Glu Arg Ser Thr Arg Thr Phe Lys Arg Val Tyr Asp Glu Val
2280 2285 2290
tac ggc gac gaa gac ctg ctg gag cag gcc aac gag cgc ttc gga 17063
Tyr Gly Asp Glu Asp Leu Leu Glu Gln Ala Asn Glu Arg Phe Gly
2295 2300 2305
gag ttt gct tac ggg aag cgt cag cgg gcg ctg ggg aag gag gac 17108
Glu Phe Ala Tyr Gly Lys Arg Gln Arg Ala Leu Gly Lys Glu Asp
2310 2315 2320
ctg ctg gcg ctg ccg ctg gac cag ggc aac ccc acc ccc agt ctg 17153
Leu Leu Ala Leu Pro Leu Asp Gln Gly Asn Pro Thr Pro Ser Leu
2325 2330 2335
aag ccc gtg acc ctg cag cag gtg ctg ccg agc agc gca ccc tcc 17198
Lys Pro Val Thr Leu Gln Gln Val Leu Pro Ser Ser Ala Pro Ser
2340 2345 2350
gag gcg aag cgg ggt ctg aag cgc gag ggc ggc gac ctg gcg ccc 17243
Glu Ala Lys Arg Gly Leu Lys Arg Glu Gly Gly Asp Leu Ala Pro
2355 2360 2365
acc gtg cag ctc atg gtg ccc aag cgg cag agg ctg gag gat gtg 17288
Thr Val Gln Leu Met Val Pro Lys Arg Gln Arg Leu Glu Asp Val
2370 2375 2380
ctg gag aaa atg aaa gta gac ccc ggt ctg cag ccg gac atc agg 17333
Leu Glu Lys Met Lys Val Asp Pro Gly Leu Gln Pro Asp Ile Arg
2385 2390 2395
gtc cgc ccc atc aag cag gtg gcg ccg ggc ctc ggc gtg cag acc 17378
Val Arg Pro Ile Lys Gln Val Ala Pro Gly Leu Gly Val Gln Thr
2400 2405 2410
gtg gac gtg gtc atc ccc acc ggc aac tcc ccc gcc gcc gcc acc 17423
Val Asp Val Val Ile Pro Thr Gly Asn Ser Pro Ala Ala Ala Thr
2415 2420 2425
act acc gct gcc tcc acg gac atg gag aca cag acc gat ccc gcc 17468
Thr Thr Ala Ala Ser Thr Asp Met Glu Thr Gln Thr Asp Pro Ala
2430 2435 2440
gca gcc gca gcc gca gcc gcc gcc gcg acc tcc tcg gcg gag gtg 17513
Ala Ala Ala Ala Ala Ala Ala Ala Ala Thr Ser Ser Ala Glu Val
2445 2450 2455
cag acg gac ccc tgg ctg ccg ccg gcg atg tca gct ccc cgc gcg 17558
Gln Thr Asp Pro Trp Leu Pro Pro Ala Met Ser Ala Pro Arg Ala
2460 2465 2470
cgt cgc ggg cgc agg aag tac ggc gcc gcc aac gcg ctc ctg ccc 17603
Arg Arg Gly Arg Arg Lys Tyr Gly Ala Ala Asn Ala Leu Leu Pro
2475 2480 2485
gag tac gcc ttg cat cct tcc atc gcg ccc acc ccc ggc tac cga 17648
Glu Tyr Ala Leu His Pro Ser Ile Ala Pro Thr Pro Gly Tyr Arg
2490 2495 2500
ggc tat acc tac cgc ccg cga aga gcc aag ggt tcc acc cgc cgt 17693
Gly Tyr Thr Tyr Arg Pro Arg Arg Ala Lys Gly Ser Thr Arg Arg
2505 2510 2515
ccc cgc cga cgc gcc gcc gcc acc acc cgc cgc cgc cgc cgc aga 17738
Pro Arg Arg Arg Ala Ala Ala Thr Thr Arg Arg Arg Arg Arg Arg
2520 2525 2530
cgc cag ccc gca ctg gct cca gtc tcc gtg agg aga gtg gcg cgc 17783
Arg Gln Pro Ala Leu Ala Pro Val Ser Val Arg Arg Val Ala Arg
2535 2540 2545
gac gga cac acc ctg gtg ctg ccc agg gcg cgc tac cac ccc agc 17828
Asp Gly His Thr Leu Val Leu Pro Arg Ala Arg Tyr His Pro Ser
2550 2555 2560
atc gtt taaaagcctg ttgtggttct tgcagat atg gcc ctc act tgc cgc 17879
Ile Val Met Ala Leu Thr Cys Arg
2565 2570
ctc cgt ttc ccg gtg ccg gga tac cga gga gga aga tcg cgc cgc 17924
Leu Arg Phe Pro Val Pro Gly Tyr Arg Gly Gly Arg Ser Arg Arg
2575 2580 2585
agg agg ggt ctg gcc ggc cgc ggc ctg agc gga ggc agc cgc cgc 17969
Arg Arg Gly Leu Ala Gly Arg Gly Leu Ser Gly Gly Ser Arg Arg
2590 2595 2600
gcg cac cgg cgg cga cgc gcc acc agc cga cgc atg cgc ggc ggg 18014
Ala His Arg Arg Arg Arg Ala Thr Ser Arg Arg Met Arg Gly Gly
2605 2610 2615
gtg ctg ccc ctg tta atc ccc ctg atc gcc gcg gcg atc ggc gcc 18059
Val Leu Pro Leu Leu Ile Pro Leu Ile Ala Ala Ala Ile Gly Ala
2620 2625 2630
gtg ccc ggg atc gcc tcc gtg gcc ttg caa gcg tcc cag agg cat 18104
Val Pro Gly Ile Ala Ser Val Ala Leu Gln Ala Ser Gln Arg His
2635 2640 2645
tgacagactt gcaaacttgc aaatatggaa aaaaacccca ataaaaaagt ctagactctc 18164
acgctcgctt ggtcctgtga ctattttgta ga atg gaa gac atc aac ttt gcg 18217
Met Glu Asp Ile Asn Phe Ala
2650
tcg ctg gcc ccg cgt cac ggc tcg cgc ccg ttc ctg gga cac tgg 18262
Ser Leu Ala Pro Arg His Gly Ser Arg Pro Phe Leu Gly His Trp
2655 2660 2665
aac gat atc ggc acc agc aac atg agc ggt ggc gcc ttc agt tgg 18307
Asn Asp Ile Gly Thr Ser Asn Met Ser Gly Gly Ala Phe Ser Trp
2670 2675 2680
ggc tct ctg tgg agc ggc att aaa agt atc ggg tct gcc gtt aaa 18352
Gly Ser Leu Trp Ser Gly Ile Lys Ser Ile Gly Ser Ala Val Lys
2685 2690 2695
aat tac ggc tcc cgg gcc tgg aac agc agc acg ggc cag atg ttg 18397
Asn Tyr Gly Ser Arg Ala Trp Asn Ser Ser Thr Gly Gln Met Leu
2700 2705 2710
aga gac aag ttg aaa gag cag aac ttc cag cag aag gtg gtg gag 18442
Arg Asp Lys Leu Lys Glu Gln Asn Phe Gln Gln Lys Val Val Glu
2715 2720 2725
ggc ctg gcc tcc ggc atc aac ggg gtg gtg gac ctg gcc aac cag 18487
Gly Leu Ala Ser Gly Ile Asn Gly Val Val Asp Leu Ala Asn Gln
2730 2735 2740
gcc gtg cag aat aag atc aac agc aga ctg gac ccc cgg ccg ccg 18532
Ala Val Gln Asn Lys Ile Asn Ser Arg Leu Asp Pro Arg Pro Pro
2745 2750 2755
gtg gag gag gtg ccg ccg gcg ctg gag acg gtg tcc ccc gat ggg 18577
Val Glu Glu Val Pro Pro Ala Leu Glu Thr Val Ser Pro Asp Gly
2760 2765 2770
cgt ggc gag aag cgc ccg cgg ccc gat agg gaa gag acc act ctg 18622
Arg Gly Glu Lys Arg Pro Arg Pro Asp Arg Glu Glu Thr Thr Leu
2775 2780 2785
gtc acg cag acc gat gag ccg ccc ccg tat gag gag gcc ctg aag 18667
Val Thr Gln Thr Asp Glu Pro Pro Pro Tyr Glu Glu Ala Leu Lys
2790 2795 2800
caa ggt ctg ccc acc acg cgg ccc atc gcg ccc atg gcc acc ggg 18712
Gln Gly Leu Pro Thr Thr Arg Pro Ile Ala Pro Met Ala Thr Gly
2805 2810 2815
gtg gtg ggc cgc cac acc ccc gcc acg ctg gac ttg cct ccg ccc 18757
Val Val Gly Arg His Thr Pro Ala Thr Leu Asp Leu Pro Pro Pro
2820 2825 2830
gcc gat gtg ccg cag cag cag aag gcg gca cag ccg ggc ccg ccc 18802
Ala Asp Val Pro Gln Gln Gln Lys Ala Ala Gln Pro Gly Pro Pro
2835 2840 2845
gcg acc gcc tcc cgt tcc tcc gcc ggt cct ctg cgc cgc gcg gcc 18847
Ala Thr Ala Ser Arg Ser Ser Ala Gly Pro Leu Arg Arg Ala Ala
2850 2855 2860
agc ggc ccc cgc ggg ggg gtc gcg agg cac ggc aac tgg cag agc 18892
Ser Gly Pro Arg Gly Gly Val Ala Arg His Gly Asn Trp Gln Ser
2865 2870 2875
acg ctg aac agc atc gtg ggt ctg ggg gtg cgg tcc gtg aag cgc 18937
Thr Leu Asn Ser Ile Val Gly Leu Gly Val Arg Ser Val Lys Arg
2880 2885 2890
cgc cga tgc tac tgaatagctt agctaacgtg ttgtatgtgt gtatgcgccc 18989
Arg Arg Cys Tyr
2895
tatgtcgccg ccagaggagc tgctgagtcg ccgccgttcg cgcgcccacc accaccgcca 19049
ctccgcccct caag atg gcg acc cca tcg atg atg ccg cag tgg tcg tac 19099
Met Ala Thr Pro Ser Met Met Pro Gln Trp Ser Tyr
2900 2905
atg cac atc tcg ggc cag gac gcc tcg gag tac ctg agc ccc ggg 19144
Met His Ile Ser Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly
2910 2915 2920
ctg gtg cag ttc gcc cgc gcc acc gag agc tac ttc agc ctg agt 19189
Leu Val Gln Phe Ala Arg Ala Thr Glu Ser Tyr Phe Ser Leu Ser
2925 2930 2935
aac aag ttt agg aac ccc acg gtg gcg ccc acg cac gat gtg acc 19234
Asn Lys Phe Arg Asn Pro Thr Val Ala Pro Thr His Asp Val Thr
2940 2945 2950
acc gac cgg tct cag cgc ctg acg ctg cgg ttc att ccc gtg gac 19279
Thr Asp Arg Ser Gln Arg Leu Thr Leu Arg Phe Ile Pro Val Asp
2955 2960 2965
cgc gag gac acc gcg tac tcg tac aag gcg cgg ttc acc ctg gcc 19324
Arg Glu Asp Thr Ala Tyr Ser Tyr Lys Ala Arg Phe Thr Leu Ala
2970 2975 2980
gtg ggc gac aac cgc gtg ctg gac atg gcc tcc acc tac ttt gac 19369
Val Gly Asp Asn Arg Val Leu Asp Met Ala Ser Thr Tyr Phe Asp
2985 2990 2995
atc cgc ggg gtg ctg gac cgg ggc ccc act ttc aag cct tac tct 19414
Ile Arg Gly Val Leu Asp Arg Gly Pro Thr Phe Lys Pro Tyr Ser
3000 3005 3010
ggc acc gcc tac aac tcc ctg gcc ccc aag ggc gct ccc aac tcc 19459
Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly Ala Pro Asn Ser
3015 3020 3025
tgc gag tgg gag caa tta gaa gaa gcc cag gcc gct gtg gaa gac 19504
Cys Glu Trp Glu Gln Leu Glu Glu Ala Gln Ala Ala Val Glu Asp
3030 3035 3040
gaa gaa tta gaa gat gaa gac gag gaa cca cag gat gag gca cct 19549
Glu Glu Leu Glu Asp Glu Asp Glu Glu Pro Gln Asp Glu Ala Pro
3045 3050 3055
gtg aaa aaa acc cat gta tac gct cag gct ccc ctt tct gga gaa 19594
Val Lys Lys Thr His Val Tyr Ala Gln Ala Pro Leu Ser Gly Glu
3060 3065 3070
gaa att act aaa aac ggt ttg caa ata ggg tca gat aac aca gaa 19639
Glu Ile Thr Lys Asn Gly Leu Gln Ile Gly Ser Asp Asn Thr Glu
3075 3080 3085
gcc cag tct aag ccc ata tat gca gat cct aca ttc cag ccc gaa 19684
Ala Gln Ser Lys Pro Ile Tyr Ala Asp Pro Thr Phe Gln Pro Glu
3090 3095 3100
ccc caa atc ggg gaa tcc cag tgg aat gag gca gat gct aca gtt 19729
Pro Gln Ile Gly Glu Ser Gln Trp Asn Glu Ala Asp Ala Thr Val
3105 3110 3115
gcc ggc ggt aga gtg cta aag aaa tcc act ccc atg aag cca tgc 19774
Ala Gly Gly Arg Val Leu Lys Lys Ser Thr Pro Met Lys Pro Cys
3120 3125 3130
tat ggt tcc tat gca aga ccc aca aac tcc aat gga ggt caa ggt 19819
Tyr Gly Ser Tyr Ala Arg Pro Thr Asn Ser Asn Gly Gly Gln Gly
3135 3140 3145
gtg ctg gtg gct gat gat aag ggg gtt ctt caa tct aaa gtt gaa 19864
Val Leu Val Ala Asp Asp Lys Gly Val Leu Gln Ser Lys Val Glu
3150 3155 3160
ttg caa ttt ttt tca aat act act act ctt aat cag cgg gag ggt 19909
Leu Gln Phe Phe Ser Asn Thr Thr Thr Leu Asn Gln Arg Glu Gly
3165 3170 3175
aac gat aca aaa cca aaa gtg gtg ctg tat agc gaa gat gtg cac 19954
Asn Asp Thr Lys Pro Lys Val Val Leu Tyr Ser Glu Asp Val His
3180 3185 3190
atg gaa act cca gac acc cac att tct tac aag ccc aca aaa agc 19999
Met Glu Thr Pro Asp Thr His Ile Ser Tyr Lys Pro Thr Lys Ser
3195 3200 3205
gat gac aat tca aaa atc atg ctg ggt cag cag tcc atg ccc aac 20044
Asp Asp Asn Ser Lys Ile Met Leu Gly Gln Gln Ser Met Pro Asn
3210 3215 3220
aga cct aat tac atc ggc ttc aga gac aac ttt atc ggc ctc atg 20089
Arg Pro Asn Tyr Ile Gly Phe Arg Asp Asn Phe Ile Gly Leu Met
3225 3230 3235
tat tac aat agc act ggc aac atg gga gtg ctt gca ggt cag gcc 20134
Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val Leu Ala Gly Gln Ala
3240 3245 3250
tct cag ttg aat gca gtg gtg gac ttg caa gac aga aac aca gaa 20179
Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp Arg Asn Thr Glu
3255 3260 3265
ctg tcc tac cag ctc ttg ctt gat tcc atg ggt gac aga acc aga 20224
Leu Ser Tyr Gln Leu Leu Leu Asp Ser Met Gly Asp Arg Thr Arg
3270 3275 3280
tac ttt tcc atg tgg aat cag gca gtg gac agt tat gac cca gat 20269
Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp Pro Asp
3285 3290 3295
gtc aga att att gaa aat cat gga act gaa gac gag ctc ccc aac 20314
Val Arg Ile Ile Glu Asn His Gly Thr Glu Asp Glu Leu Pro Asn
3300 3305 3310
tat tgt ttc cct ctg ggc ggc ata ggg gta act gac act tac cag 20359
Tyr Cys Phe Pro Leu Gly Gly Ile Gly Val Thr Asp Thr Tyr Gln
3315 3320 3325
gcc att aaa acc aat ggc aat ggt caa gaa aac cca acc tgg gaa 20404
Ala Ile Lys Thr Asn Gly Asn Gly Gln Glu Asn Pro Thr Trp Glu
3330 3335 3340
aaa gat aca gag ttt gca gac cgc aat gaa ata ggg gtg gga aac 20449
Lys Asp Thr Glu Phe Ala Asp Arg Asn Glu Ile Gly Val Gly Asn
3345 3350 3355
aat ttc gct atg gag atc aac ctc agt gcc aac ctg tgg aga aac 20494
Asn Phe Ala Met Glu Ile Asn Leu Ser Ala Asn Leu Trp Arg Asn
3360 3365 3370
ttc ctg tac tcc aac gtg gcg ctg tac cta cca gac aag ctt aag 20539
Phe Leu Tyr Ser Asn Val Ala Leu Tyr Leu Pro Asp Lys Leu Lys
3375 3380 3385
tac aac ccc tcc aat gtg gac atc tct gac aac ccc aac acc tac 20584
Tyr Asn Pro Ser Asn Val Asp Ile Ser Asp Asn Pro Asn Thr Tyr
3390 3395 3400
gat tac atg aac aag cga gtg gtg gcc ccg ggg ctg gtg gac tgc 20629
Asp Tyr Met Asn Lys Arg Val Val Ala Pro Gly Leu Val Asp Cys
3405 3410 3415
tac atc aac ctg ggc gcg cgc tgg tcg ctg gac tac atg gac aac 20674
Tyr Ile Asn Leu Gly Ala Arg Trp Ser Leu Asp Tyr Met Asp Asn
3420 3425 3430
gtg aac ccc ttc aac cac cac cgc aat gcg ggc ctg cgc tac cgc 20719
Val Asn Pro Phe Asn His His Arg Asn Ala Gly Leu Arg Tyr Arg
3435 3440 3445
tcc atg ctc ctg ggc aac ggg cgc tac gtg ccc ttc cac atc cag 20764
Ser Met Leu Leu Gly Asn Gly Arg Tyr Val Pro Phe His Ile Gln
3450 3455 3460
gtg ccc cag aag ttc ttt gcc atc aag aac ctc ctc ctc ctg ccg 20809
Val Pro Gln Lys Phe Phe Ala Ile Lys Asn Leu Leu Leu Leu Pro
3465 3470 3475
ggc tcc tac acc tac gag tgg aac ttc agg aag gat gtc aac atg 20854
Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg Lys Asp Val Asn Met
3480 3485 3490
gtc ctc cag agc tct ctg ggt aac gat ctc agg gtg gac ggg gcc 20899
Val Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg Val Asp Gly Ala
3495 3500 3505
agc atc aag ttc gag agc atc tgc ctc tac gcc acc ttc ttc ccc 20944
Ser Ile Lys Phe Glu Ser Ile Cys Leu Tyr Ala Thr Phe Phe Pro
3510 3515 3520
atg gcc cac aac acg gcc tcc acg ctc gag gcc atg ctc agg aac 20989
Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu Arg Asn
3525 3530 3535
gac acc aac gac cag tcc ttc aat gac tac ctc tcc gcc gcc aac 21034
Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala Asn
3540 3545 3550
atg ctc tac ccc ata ccc gcc aac gcc acc aac gtc ccc atc tcc 21079
Met Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Val Pro Ile Ser
3555 3560 3565
atc ccc tcg cgc aac tgg gcg gcc ttc cgc ggc tgg gcc ttc acc 21124
Ile Pro Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ala Phe Thr
3570 3575 3580
cgc ctc aag acc aag gag acc ccc tcc ctg ggc tcg gga ttc gac 21169
Arg Leu Lys Thr Lys Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp
3585 3590 3595
ccc tac tac acc tac tcg ggc tcc att ccc tac ctg gac ggc acc 21214
Pro Tyr Tyr Thr Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr
3600 3605 3610
ttc tac ctc aac cac act ttc aag aag gtc tcg gtc acc ttc gac 21259
Phe Tyr Leu Asn His Thr Phe Lys Lys Val Ser Val Thr Phe Asp
3615 3620 3625
tcc tcg gtc agc tgg ccg ggc aac gac cgt ctg ctc acc ccc aac 21304
Ser Ser Val Ser Trp Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn
3630 3635 3640
gag ttc gag atc aag cgc tcg gtc gac ggg gag ggc tac aac gtg 21349
Glu Phe Glu Ile Lys Arg Ser Val Asp Gly Glu Gly Tyr Asn Val
3645 3650 3655
gcc cag tgc aac atg acc aag gac tgg ttc ctg gtc cag atg ctg 21394
Ala Gln Cys Asn Met Thr Lys Asp Trp Phe Leu Val Gln Met Leu
3660 3665 3670
gcc aac tac aac atc ggc tac cag ggc ttc tac atc cca gag agc 21439
Ala Asn Tyr Asn Ile Gly Tyr Gln Gly Phe Tyr Ile Pro Glu Ser
3675 3680 3685
tac aag gac agg atg tac tcc ttc ttc agg aac ttc cag ccc atg 21484
Tyr Lys Asp Arg Met Tyr Ser Phe Phe Arg Asn Phe Gln Pro Met
3690 3695 3700
agc cgg cag gtg gtg gac cag acc aag tac aag gac tac cag gag 21529
Ser Arg Gln Val Val Asp Gln Thr Lys Tyr Lys Asp Tyr Gln Glu
3705 3710 3715
gtg ggc atc atc cac cag cac aac aac tcg ggc ttc gtg ggc tac 21574
Val Gly Ile Ile His Gln His Asn Asn Ser Gly Phe Val Gly Tyr
3720 3725 3730
ctc gcc ccc acc atg cgc gag gga cag gcc tac ccc gcc aac ttc 21619
Leu Ala Pro Thr Met Arg Glu Gly Gln Ala Tyr Pro Ala Asn Phe
3735 3740 3745
ccc tat ccg ctc ata ggc aag acc gcg gtc gac agc atc acc cag 21664
Pro Tyr Pro Leu Ile Gly Lys Thr Ala Val Asp Ser Ile Thr Gln
3750 3755 3760
aaa aag ttc ctc tgc gac cgc acc ctc tgg cgc atc ccc ttc tcc 21709
Lys Lys Phe Leu Cys Asp Arg Thr Leu Trp Arg Ile Pro Phe Ser
3765 3770 3775
agc aac ttc atg tcc atg ggt gcg ctc tcg gac ctg ggc cag aac 21754
Ser Asn Phe Met Ser Met Gly Ala Leu Ser Asp Leu Gly Gln Asn
3780 3785 3790
ttg ctc tac gcc aac tcc gcc cac gcc ctc gac atg acc ttc gag 21799
Leu Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Thr Phe Glu
3795 3800 3805
gtc gac ccc atg gac gag ccc acc ctt ctc tat gtt ctg ttc gaa 21844
Val Asp Pro Met Asp Glu Pro Thr Leu Leu Tyr Val Leu Phe Glu
3810 3815 3820
gtc ttt gac gtg gtc cgg gtc cac cag ccg cac cgc ggc gtc atc 21889
Val Phe Asp Val Val Arg Val His Gln Pro His Arg Gly Val Ile
3825 3830 3835
gag acc gtg tac ctg cgt acg ccc ttc tcg gcc ggc aac gcc acc 21934
Glu Thr Val Tyr Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr
3840 3845 3850
acc taaagaagca agccgcagtc atcgccgcct gc atg ccg tcg ggt tcc acc 21987
Thr Met Pro Ser Gly Ser Thr
3855 3860
gag caa gag ctc agg gcc atc gtc aga gac ctg gga tgc ggg ccc 22032
Glu Gln Glu Leu Arg Ala Ile Val Arg Asp Leu Gly Cys Gly Pro
3865 3870 3875
tat ttt ttg ggc acc ttc gac aag cgc ttc cct ggc ttt gtc tcc 22077
Tyr Phe Leu Gly Thr Phe Asp Lys Arg Phe Pro Gly Phe Val Ser
3880 3885 3890
cca cac aag ctg gcc tgc gcc atc gtc aac acg gcc ggc cgc gag 22122
Pro His Lys Leu Ala Cys Ala Ile Val Asn Thr Ala Gly Arg Glu
3895 3900 3905
acc ggg ggc gtg cac tgg ctg gcc ttc gcc tgg aac ccg cgc tcc 22167
Thr Gly Gly Val His Trp Leu Ala Phe Ala Trp Asn Pro Arg Ser
3910 3915 3920
aaa aca tgc ttc ctc ttt gac ccc ttc ggc ttt tcg gac cag cgg 22212
Lys Thr Cys Phe Leu Phe Asp Pro Phe Gly Phe Ser Asp Gln Arg
3925 3930 3935
ctc aag caa atc tac gag ttc gag tac gag ggc ttg ctg cgt cgc 22257
Leu Lys Gln Ile Tyr Glu Phe Glu Tyr Glu Gly Leu Leu Arg Arg
3940 3945 3950
agc gcc atc gcc tcc tcg ccc gac cgc tgc gtc acc ctc gaa aag 22302
Ser Ala Ile Ala Ser Ser Pro Asp Arg Cys Val Thr Leu Glu Lys
3955 3960 3965
tcc acc cag acc gtg cag ggg ccc gac tcg gcc gcc tgc ggt ctc 22347
Ser Thr Gln Thr Val Gln Gly Pro Asp Ser Ala Ala Cys Gly Leu
3970 3975 3980
ttc tgc tgc atg ttt ctg cac gcc ttt gtg cac tgg cct cag agt 22392
Phe Cys Cys Met Phe Leu His Ala Phe Val His Trp Pro Gln Ser
3985 3990 3995
ccc atg gac cgc aac ccc acc atg aac ttg ctg acg ggg gtg ccc 22437
Pro Met Asp Arg Asn Pro Thr Met Asn Leu Leu Thr Gly Val Pro
4000 4005 4010
aac tcc atg ctc cag agc ccc cag gtc gag ccc acc ctg cgc cgc 22482
Asn Ser Met Leu Gln Ser Pro Gln Val Glu Pro Thr Leu Arg Arg
4015 4020 4025
aac cag gag cag ctc tac agc ttc ctg gag cgc cac tcg cct tac 22527
Asn Gln Glu Gln Leu Tyr Ser Phe Leu Glu Arg His Ser Pro Tyr
4030 4035 4040
ttc cgc cgc cac agc gca cag atc agg agg gcc acc tcc ttc tgc 22572
Phe Arg Arg His Ser Ala Gln Ile Arg Arg Ala Thr Ser Phe Cys
4045 4050 4055
cac ttg caa gag atg caa gaa ggg taataacgat gtacacactt tttttctcaa 22626
His Leu Gln Glu Met Gln Glu Gly
4060
taaatggcat ctttttattt atacaagctc tctggggtat tcatttccca ccaccacccg 22686
ccgttgtcgc catctggctc tatttagaaa tcgaaagggt tctgccggga gtcgccgtgc 22746
gccacgggca gggacacgtt gcgatactgg tagcgggtgc cccacttgaa ctcgggcacc 22806
accaggcgag gcagctcggg gaagttttcg ctccacaggc tgcgggtcag caccagcgcg 22866
ttcatcaggt cgggcgccga gatcttgaag tcgcagttgg ggccgccgcc ctgcgcgcgc 22926
gagttgcggt acaccgggtt gcagcactgg aacaccaaca gcgccgggtg cttcacgctg 22986
gccagcacgc tgcggtcgga gatcagctcg gcgtccaggt cctccgcgtt gctcagcgcg 23046
aacggggtca tcttgggcac ttgccgcccc aggaagggcg cgtgccccgg tttcgagttg 23106
cagtcgcagc gcagcgggat cagcaggtgc ccgtgcccgg actcggcgtt ggggtacagc 23166
gcgcgcatga aggcctgcat ctggcggaag gccatctggg ccttggcgcc ctccgagaag 23226
aacatgccgc aggacttgcc cgagaactgg tttgcggggc agctggcgtc gtgcaggcag 23286
cagcgcgcgt cggtgttggc gatctgcacc acgttgcgcc cccaccggtt cttcacgatc 23346
ttggccttgg acgattgctc cttcagcgcg cgctgcccgt tctcgctggt cacatccatc 23406
tcgatcacat gttccttgtt caccatgctg ctgccgtgca gacacttcag ctcgccctcc 23466
gtctcggtgc agcggtgctg ccacagcgcg cagcccgtgg gctcgaaaga cttgtaggtc 23526
acctccgcga aggactgcag gtacccctgc aaaaagcggc ccatcatggt cacgaaggtc 23586
ttgttgctgc tgaaggtcag ctgcagcccg cggtgctcct cgttcagcca ggtcttgcac 23646
acggccgcca gcgcctccac ctggtcgggc agcatcttga agttcacctt tagctcattc 23706
tccacgtggt acttgtccat tagcgcgcgc gccgcctcca tgcccttctc ccaggccgac 23766
accagcggca ggctcacggg gttcttcacc atcaccgtgg ccgccgcctc cgccgcgctt 23826
tcgctttccg ccccgctgtt ctcttcctct tcctcctctt cctcgccgcc gcccactcgc 23886
agcccccgca ccacggggtc gtcttcctgc aggcgctgca ccttgcgctt gccgttgcgc 23946
ccctgcttga tgcgcacggg cgggttgctg aagcccacca tcaccagcgc ggcctcttct 24006
tgctcgtcct cgctgtccag aatgacctcc ggggaggggg ggttggtcat cctcagtacc 24066
gaggcacgct tctttttctt cctgggggcg ttcgccagct ccgcggctgc ggccgctgcc 24126
gaggtcgaag gccgagggct gggcgtgcgc ggcaccagcg cgtcttgcga gccgtcctcg 24186
tcctcctcgg actcgagacg gaggcgggcc cgcttcttcg ggggcgcgcg gggcggcgga 24246
ggcggcggcg gcgacggaga cggggacgag acatcgtcca gggtgggtgg acggcgggcc 24306
gcgccgcgtc cgcgctcggg ggtggtctcg cgctggtcct cttcccgact ggccatctcc 24366
cactgctcct tctcctatag gcagaaagag atcatggagt ctctcatgcg agtcgagaag 24426
gaggaggaca gcctaaccgc cccctctgag ccctccacca ccgccgccac caccgccaat 24486
gccgccgcgg acgacgcgcc caccgagacc accgccagta ccaccctccc cagcgacgca 24546
cccccgctcg agaatgaagt gctgatcgag caggacccgg gttttgtgag cggagaggag 24606
gatgaggtgg atgagaagga gaaggaggag gtcgccgcct cagtgccaaa agaggataaa 24666
aagcaagacc aggacgacgc agataaggat gagacagcag tcgggcgggg gaacggaagc 24726
catgatgctg atgacggcta cctagacgtg ggagacgacg tgctgcttaa gcacctgcac 24786
cgccagtgcg tcatcgtctg cgacgcgctg caggagcgct gcgaagtgcc cctggacgtg 24846
gcggaggtca gccgcgccta cgagcggcac ctcttcgcgc cgcacgtgcc ccccaagcgc 24906
cgggagaacg gcacctgcga gcccaacccg cgtctcaact tctacccggt cttcgcggta 24966
cccgaggtgc tggccaccta ccacatcttc ttccaaaact gcaagatccc cctctcctgc 25026
cgcgctaacc gcacccgcgc cgacaaaacc ctgaccctgc ggcagggcgc ccacatacct 25086
gatattgcct ctctggagga agtgcccaag atcttcgagg gtctcggtcg cgacgagaaa 25146
cgggcggcga acgctctgca cggagacagc gaaaacgaga gtcactcggg ggtgctggtg 25206
gagctcgagg gcgacaacgc gcgcctggcc gtactcaagc gcagcataga ggtcacccac 25266
tttgcctacc cggcgctcaa cctgcccccc aaggtcatga gtgtggtcat gggcgagctc 25326
atcatgcgcc gcgcccagcc cctggccgcg gatgcaaact tgcaagagtc ctcagaggaa 25386
ggcctgcccg cggtcagcga cgagcagctg gcgcgctggc tggagacccg cgaccccgcg 25446
cagctggagg agcggcgcaa gctcatgatg gccgcggtgc tggtcaccgt ggagctcgag 25506
tgtctgcagc gcttcttcgc ggaccccgag atgcagcgca agctcgagga gaccctgcac 25566
tacaccttcc gccagggcta cgtgcgccag gcctgcaaga tctccaacgt ggagctctgc 25626
aacctggtct cctacctggg catcctgcac gagaaccgcc tcgggcagaa cgtcctgcac 25686
tccaccctca aaggggaggc gcgccgcgac tacatccgcg actgcgccta cctcttcctc 25746
tgctacacct ggcagacggc tatgggggtc tggcagcagt gcctggagga gcgcaacctc 25806
aaggagctgg aaaagctcct caagcgcacc ctcagggacc tctggacggg cttcaacgag 25866
cgctcggtgg ccgccgcgct ggcggacatc atcttccccg agcgcttgct caagaccctg 25926
cagcagggcc tgccagactt caccagccag agcatgctgc agaacttcag gactttcatc 25986
cttgagcgct cgggcatcct gccggccact tgctgcgcgc tgcccagcga cttcgtgccc 26046
atcaagtaca gggagtgccc gccgccgctc tggggccact gctacctctt ccagctggcc 26106
aactacctcg cctaccactc ggacctcatg gaagacgtga gcggcgaggg cctgctcgag 26166
tgccactgcc gctgcaacct ctgcacgccc caccgctctc tagtctgcaa cccgcagctg 26226
ctcagcgaga gtcagattat cggtaccttc gagctgcagg gtccctcgcc tgacgagaag 26286
tccgcggctc cggggctgaa actcactccg gggctgtgga cttccgccta cctacgcaaa 26346
tttgtacctg aggactacca cgcccacgag atcaggttct acgaagacca atcccgcccg 26406
cccaaggcgg agctcaccgc ctgcgtcatc acccaggggc acatcctggg ccaattgcaa 26466
gccatcaaca aagcccgccg agagttcttg ctgaaaaagg gtcggggggt gtacctggac 26526
ccccagtccg gcgaggagct aaacccgcta cccccgccgc cgccccagca gcgggacctt 26586
gcttcccagg atg gca ccc aga aag aag cag cag ccg ccg ccg cag cca 26635
Met Ala Pro Arg Lys Lys Gln Gln Pro Pro Pro Gln Pro
4065 4070 4075
tac atg ctt ctg gag gaa gag gag gag gac tgg gac agt cag gca 26680
Tyr Met Leu Leu Glu Glu Glu Glu Glu Asp Trp Asp Ser Gln Ala
4080 4085 4090
gag gag gtt tcg gac gag gag cag gag gag atg atg gaa gac tgg 26725
Glu Glu Val Ser Asp Glu Glu Gln Glu Glu Met Met Glu Asp Trp
4095 4100 4105
gag gag gac agc agc cta gac gag gaa gct tca gag gcc gaa gag 26770
Glu Glu Asp Ser Ser Leu Asp Glu Glu Ala Ser Glu Ala Glu Glu
4110 4115 4120
gtg gca gac gca aca cca tca ccc tcg gtc gca gcc ccc tcg ccg 26815
Val Ala Asp Ala Thr Pro Ser Pro Ser Val Ala Ala Pro Ser Pro
4125 4130 4135
ggg ccc ctg aaa tcc tcc gaa ccc agc acc agc gct ata acc tcc 26860
Gly Pro Leu Lys Ser Ser Glu Pro Ser Thr Ser Ala Ile Thr Ser
4140 4145 4150
gct cct ccg gcg ccg gcg cca ccc gcc cgc aga ccc aac cgt aga 26905
Ala Pro Pro Ala Pro Ala Pro Pro Ala Arg Arg Pro Asn Arg Arg
4155 4160 4165
tgg gac acc aca gga acc ggg gtc ggt aag tcc aag tgc ccg ccg 26950
Trp Asp Thr Thr Gly Thr Gly Val Gly Lys Ser Lys Cys Pro Pro
4170 4175 4180
ccg cca ccg cag cag cag cag cag cag cgc cag ggc tac cgc tcg 26995
Pro Pro Pro Gln Gln Gln Gln Gln Gln Arg Gln Gly Tyr Arg Ser
4185 4190 4195
tgg cgc ggg cac aag aac gcc ata gtc gcc tgc ttg caa gac tgc 27040
Trp Arg Gly His Lys Asn Ala Ile Val Ala Cys Leu Gln Asp Cys
4200 4205 4210
ggg ggc aac atc tct ttc gcc cgc cgc ttc ctg cta ttc cac cac 27085
Gly Gly Asn Ile Ser Phe Ala Arg Arg Phe Leu Leu Phe His His
4215 4220 4225
ggg gtc gcc ttt ccc cgc aat gtc ctg cat tac tac cgt cat ctc 27130
Gly Val Ala Phe Pro Arg Asn Val Leu His Tyr Tyr Arg His Leu
4230 4235 4240
tac agc ccc tac tgc agc ggc gac cca gag gcg gca gcg gca gcc 27175
Tyr Ser Pro Tyr Cys Ser Gly Asp Pro Glu Ala Ala Ala Ala Ala
4245 4250 4255
aca gcg gcg acc acc acc taggaagata tcctccgcgg gcaagacagc 27223
Thr Ala Ala Thr Thr Thr
4260
ggcagcagcg gccaggagac ccgcggcagc agcggcggga gcggtgggcg cactgcgcct 27283
ctcgcccaac gaacccctct cgacccggga gctcagacac aggatcttcc ccactttgta 27343
tgccatcttc caacagagca gaggccagga gcaggagctg aaaataaaaa acagatctct 27403
gcgctccctc acccgcagct gtctgtatca caaaagcgaa gatcagcttc ggcgcacgct 27463
ggaggacgcg gaggcactct tcagcaaata ctgcgcgctc actcttaaag actagctccg 27523
cgcccttctc gaatttaggc gggagaaaac tacgtcatcg ccggccgccg cccagcccgc 27583
ccagccgag atg agc aaa gag att ccc acg cca tac atg tgg agc tac 27631
Met Ser Lys Glu Ile Pro Thr Pro Tyr Met Trp Ser Tyr
4265 4270 4275
cag ccg cag atg gga ctc gcg gcg gga gcg gcc cag gac tac tcc 27676
Gln Pro Gln Met Gly Leu Ala Ala Gly Ala Ala Gln Asp Tyr Ser
4280 4285 4290
acc cgc atg aac tac atg agc gcg gga ccc cac atg atc tca cag 27721
Thr Arg Met Asn Tyr Met Ser Ala Gly Pro His Met Ile Ser Gln
4295 4300 4305
gtc aac ggg atc cgc gcc cag cga aac caa ata ctg ctg gaa cag 27766
Val Asn Gly Ile Arg Ala Gln Arg Asn Gln Ile Leu Leu Glu Gln
4310 4315 4320
gcg gcc atc acc gcc acg ccc cgc cat aat ctc aac ccc cga aat 27811
Ala Ala Ile Thr Ala Thr Pro Arg His Asn Leu Asn Pro Arg Asn
4325 4330 4335
tgg ccc gcc gcc ctc gtg tac cag gaa acc ccc tcc gcc acc acc 27856
Trp Pro Ala Ala Leu Val Tyr Gln Glu Thr Pro Ser Ala Thr Thr
4340 4345 4350
gta cta ctt ccg cgt gac gcc cag gcc gaa gtc cag atg act aac 27901
Val Leu Leu Pro Arg Asp Ala Gln Ala Glu Val Gln Met Thr Asn
4355 4360 4365
tca ggg gcg cag ctc gcg ggc ggc ttt cgt cac ggg gcg cgg ccg 27946
Ser Gly Ala Gln Leu Ala Gly Gly Phe Arg His Gly Ala Arg Pro
4370 4375 4380
ctc cga cca ggt ata aga cac ctg atg atc aga ggc cga ggt atc 27991
Leu Arg Pro Gly Ile Arg His Leu Met Ile Arg Gly Arg Gly Ile
4385 4390 4395
cag ctc aac gac gag tcg gtg agc tct tcg ctc ggt ctc cgt ccg 28036
Gln Leu Asn Asp Glu Ser Val Ser Ser Ser Leu Gly Leu Arg Pro
4400 4405 4410
gac gga act ttc cag ctc gcc gga tcc ggc cgc tct tcg ttc acg 28081
Asp Gly Thr Phe Gln Leu Ala Gly Ser Gly Arg Ser Ser Phe Thr
4415 4420 4425
ccc cgc cag gcg tac ctg act ctg cag acc tcg tcc tcg gag ccc 28126
Pro Arg Gln Ala Tyr Leu Thr Leu Gln Thr Ser Ser Ser Glu Pro
4430 4435 4440
cgc tcc gga ggc atc gga acc ctc cag ttc gtg gag gag ttc gtg 28171
Arg Ser Gly Gly Ile Gly Thr Leu Gln Phe Val Glu Glu Phe Val
4445 4450 4455
ccc tcg gtc tac ttc aac ccc ttc tcg gga cct ccc gga cgc tac 28216
Pro Ser Val Tyr Phe Asn Pro Phe Ser Gly Pro Pro Gly Arg Tyr
4460 4465 4470
ccc gac cag ttc att ccg aac ttt gac gcg gtg aag gac tcg gcg 28261
Pro Asp Gln Phe Ile Pro Asn Phe Asp Ala Val Lys Asp Ser Ala
4475 4480 4485
gac ggc tac gac tga atg tca ggt gcc gag gca gag cag ctt cgc 28306
Asp Gly Tyr Asp Met Ser Gly Ala Glu Ala Glu Gln Leu Arg
4490 4495
ctg aga cac ctc gag cac tgc cgc cgc cac aag tgc ttc gcc cgc 28351
Leu Arg His Leu Glu His Cys Arg Arg His Lys Cys Phe Ala Arg
4500 4505 4510
ggt tcc ggt gag ttc tgc tac ttt cag cta ccc gag gag cat acc 28396
Gly Ser Gly Glu Phe Cys Tyr Phe Gln Leu Pro Glu Glu His Thr
4515 4520 4525
gag ggg ccg gcg cac ggc gtc cgc ctg acc acc cag ggc gag gtt 28441
Glu Gly Pro Ala His Gly Val Arg Leu Thr Thr Gln Gly Glu Val
4530 4535 4540
acc tgt tcc ctc atc cgg gag ttc acc ctc cgt ccc ctg cta gtg 28486
Thr Cys Ser Leu Ile Arg Glu Phe Thr Leu Arg Pro Leu Leu Val
4545 4550 4555
gag cgg gag cgg ggt ccc tgt gtc cta act atc gcc tgc aac tgc 28531
Glu Arg Glu Arg Gly Pro Cys Val Leu Thr Ile Ala Cys Asn Cys
4560 4565 4570
cct aac cct gga tta cat caa gat ctt tgc tgt cat ctc tgt gct 28576
Pro Asn Pro Gly Leu His Gln Asp Leu Cys Cys His Leu Cys Ala
4575 4580 4585
gag ttt aat aaa cgc tgagatcaga atctactggg gctcctgtcg ccatcctgtg 28631
Glu Phe Asn Lys Arg
4590
aacgccaccg tcttcaccca ccccgaccag gcccaggcga acctcacctg cggtctgcat 28691
cggagggcca agaagtacct cacctggtac ttcaacggca ccccctttgt ggtttacaac 28751
agcttcgacg gggacggagt ctccctgaaa gaccagctct ccggtctcag ctactccatc 28811
cacaagaaca ccaccctcca actcttccct ccctacctgc cgggaaccta cgagtgcgtc 28871
accggccgct gcacccacct cacccgcctg atcgtaaacc agagctttcc gggaacagat 28931
aactccctct tccccagaac aggaggtgag ctcaggaaac tccccgggga ccagggcgga 28991
gacgtacctt cgacccttgt ggggttagga ttttttatta ccgggttgct ggctctttta 29051
atcaaagctt ccttgagatt tgttctttcc ttctacgtgt atgaacacct cagcctccaa 29111
taactctacc ctttcttcgg aatcaggtga cttctctgaa atcgggcttg gtgtgctgct 29171
tactctgttg atttttttcc ttatcatact cagccttct gtg cct cag gct cgc 29225
Val Pro Gln Ala Arg
4595
cgc ctg ctg cgc aca cat cta tat cta ctg ctg gtt gct caa gtg 29270
Arg Leu Leu Arg Thr His Leu Tyr Leu Leu Leu Val Ala Gln Val
4600 4605 4610
cag ggg tcg cca ccc aag atg aac agg tac atg gtc cta tcg atc 29315
Gln Gly Ser Pro Pro Lys Met Asn Arg Tyr Met Val Leu Ser Ile
4615 4620 4625
cta ggc ctg ctg gcc ctg gcg gcc tgc agc gcc gcc aaa aaa gag 29360
Leu Gly Leu Leu Ala Leu Ala Ala Cys Ser Ala Ala Lys Lys Glu
4630 4635 4640
att acc ttt gag gag ccc gct tgc aat gta act ttc aag ccc gag 29405
Ile Thr Phe Glu Glu Pro Ala Cys Asn Val Thr Phe Lys Pro Glu
4645 4650 4655
ggt gac caa tgc acc acc ctc gtc aaa tgc gtt acc aat cat gag 29450
Gly Asp Gln Cys Thr Thr Leu Val Lys Cys Val Thr Asn His Glu
4660 4665 4670
agg ctg cgc atc gac tac aaa aac aaa act ggc cgg ttt gcg gtc 29495
Arg Leu Arg Ile Asp Tyr Lys Asn Lys Thr Gly Arg Phe Ala Val
4675 4680 4685
tat agt gtg ttt acg ccc gga gac ccc tct aac tac tct gtc acc 29540
Tyr Ser Val Phe Thr Pro Gly Asp Pro Ser Asn Tyr Ser Val Thr
4690 4695 4700
gtc ttc cag ggc gga cag tct aag ata ttc aat tac act ttc cct 29585
Val Phe Gln Gly Gly Gln Ser Lys Ile Phe Asn Tyr Thr Phe Pro
4705 4710 4715
ttt tat gag ttg tgc gat gcg gtc atg tac atg tca aaa cag tac 29630
Phe Tyr Glu Leu Cys Asp Ala Val Met Tyr Met Ser Lys Gln Tyr
4720 4725 4730
aac ctg tgg cct ccc tct ccc cag gcg tgt gtg gaa aat act ggg 29675
Asn Leu Trp Pro Pro Ser Pro Gln Ala Cys Val Glu Asn Thr Gly
4735 4740 4745
tct tac tgc tgt atg gct ttc gca atc act acg ctc gct cta atc 29720
Ser Tyr Cys Cys Met Ala Phe Ala Ile Thr Thr Leu Ala Leu Ile
4750 4755 4760
tgc acg gtg cta tat ata aaa ttc agg cag agg cga atc ttt atc 29765
Cys Thr Val Leu Tyr Ile Lys Phe Arg Gln Arg Arg Ile Phe Ile
4765 4770 4775
gat gaa aag aaa atg cct tgatcgctaa caccggcttt ctatctgcag a atg 29817
Asp Glu Lys Lys Met Pro Met
4780 4785
aat gca atc acc tcc cta cta atc acc acc acc ctc ctt gcg att 29862
Asn Ala Ile Thr Ser Leu Leu Ile Thr Thr Thr Leu Leu Ala Ile
4790 4795 4800
gcc cat ggg ttg aca cga atc gaa gtg cca gtg ggg tcc aat gtc 29907
Ala His Gly Leu Thr Arg Ile Glu Val Pro Val Gly Ser Asn Val
4805 4810 4815
acc atg gtg ggc ccc gcc ggc aat tcc acc ctc atg tgg gaa aaa 29952
Thr Met Val Gly Pro Ala Gly Asn Ser Thr Leu Met Trp Glu Lys
4820 4825 4830
ttt gtc cgc aat caa tgg gtt cat ttc tgc tct aac cga atc agt 29997
Phe Val Arg Asn Gln Trp Val His Phe Cys Ser Asn Arg Ile Ser
4835 4840 4845
atc aag ccc aga gcc atc tgc gat ggg caa aat cta act ctg atc 30042
Ile Lys Pro Arg Ala Ile Cys Asp Gly Gln Asn Leu Thr Leu Ile
4850 4855 4860
aat gtg caa atg atg gat gct ggg tac tat tac ggg cag cgg gga 30087
Asn Val Gln Met Met Asp Ala Gly Tyr Tyr Tyr Gly Gln Arg Gly
4865 4870 4875
gaa atc att aat tac tgg cga ccc cac aag gac tac atg ctg cat 30132
Glu Ile Ile Asn Tyr Trp Arg Pro His Lys Asp Tyr Met Leu His
4880 4885 4890
gta gtc gag gca ctt ccc act acc acc ccc act acc acc tct ccc 30177
Val Val Glu Ala Leu Pro Thr Thr Thr Pro Thr Thr Thr Ser Pro
4895 4900 4905
acc acc acc act act act act acc act acc gct gcc cgt cat acc 30222
Thr Thr Thr Thr Thr Thr Thr Thr Thr Thr Ala Ala Arg His Thr
4910 4915 4920
cgc aaa agc acc atg att agc aca aag ccc cct cgt gct cac tcc 30267
Arg Lys Ser Thr Met Ile Ser Thr Lys Pro Pro Arg Ala His Ser
4925 4930 4935
cac gcc ggc ggg ccc atc ggt gcg acc tca gaa acc acc gag ctt 30312
His Ala Gly Gly Pro Ile Gly Ala Thr Ser Glu Thr Thr Glu Leu
4940 4945 4950
tgc ttc tgc caa tgc act aac gcc agc gct cat gaa ctg ttc gac 30357
Cys Phe Cys Gln Cys Thr Asn Ala Ser Ala His Glu Leu Phe Asp
4955 4960 4965
ctg gag aat gag gat gcc cag cag agc tcc gct tgc ctg acc cag 30402
Leu Glu Asn Glu Asp Ala Gln Gln Ser Ser Ala Cys Leu Thr Gln
4970 4975 4980
gag gct gtg gag ccc gtt gcc ctg aag cag atc ggt gat tca ata 30447
Glu Ala Val Glu Pro Val Ala Leu Lys Gln Ile Gly Asp Ser Ile
4985 4990 4995
att gac tct tct tct ttt gcc act ccc gaa tac cct ccc gat tct 30492
Ile Asp Ser Ser Ser Phe Ala Thr Pro Glu Tyr Pro Pro Asp Ser
5000 5005 5010
act ttc cac atc acg ggt acc aaa gac cct aac ctc tct ttc tac 30537
Thr Phe His Ile Thr Gly Thr Lys Asp Pro Asn Leu Ser Phe Tyr
5015 5020 5025
ctg atg ctg ctg ctc tgt atc tct gtg gtc tct tcc gcg ctg atg 30582
Leu Met Leu Leu Leu Cys Ile Ser Val Val Ser Ser Ala Leu Met
5030 5035 5040
tta ctg ggg atg ttc tgc tgc ctg atc tgc cgc aga aag aga aaa 30627
Leu Leu Gly Met Phe Cys Cys Leu Ile Cys Arg Arg Lys Arg Lys
5045 5050 5055
gct cgc tct cag ggc caa cca ctg atg ccc ttc ccc tac ccc ccg 30672
Ala Arg Ser Gln Gly Gln Pro Leu Met Pro Phe Pro Tyr Pro Pro
5060 5065 5070
gat ttt gca gat aac aag ata tgagctcgct gctgacacta accgctttac 30723
Asp Phe Ala Asp Asn Lys Ile
5075
tagcctgcgc tctaaccctt gtcgcttgcg actcgagatt ccacaatgtc acagctgtgg 30783
caggagaaaa tgttactttc aactccacgg ccgataccca gtggtcgtgg agtggctcag 30843
gtagctactt aactatctgc aatagctcca cttcccccag catatcccca accaagtacc 30903
aatgcaatgc cagcctgttc accctcatca acgcttccac cctggacaat ggactctatg 30963
taggctatgt accctttggt gggcaaggaa agacccacgc ttacaacctg gaagttcgcc 31023
agcccagaac cactacccaa gcttctccca ccaccaccac caccaccacc atcaccagca 31083
gcagcagcag cagcagccac agcagcagca gcagattatt gactttggtt ttggccagct 31143
catctgccgc tacccaggcc atctacagct ctgtgcccga aaccactcag atctaccgcc 31203
cagaaacgac caccgccacc accctacaca cctccagcga tcagatgccg accaacatca 31263
cccccttggc tcttcaaatg ggacttacaa gccccactcc aaaaccagtg gatgcggccg 31323
aggtctccgc cctcgtcaat gactgggcgg ggctgggaat gtggtggttc gccataggca 31383
tgatggcgct ctgcctgctt ctgctctggc tcatctgctg cctccaccgc aggcgagcca 31443
gaccccccat ctatagaccc atcattgtcc tgaaccccga taatgatggg atccatagat 31503
tggatggcct gaaaaaccta cttttttctt ttacagtatg ataaattgag ac atg 31558
Met
cct cgc att ttc ttg tac atg ttc ctt ctc cca cct ttt ctg ggg 31603
Pro Arg Ile Phe Leu Tyr Met Phe Leu Leu Pro Pro Phe Leu Gly
5080 5085 5090
tgt tct acg ctg gcc gct gtg tct cac ctg gag gta gac tgc ctc 31648
Cys Ser Thr Leu Ala Ala Val Ser His Leu Glu Val Asp Cys Leu
5095 5100 5105
tca ccc ttc act gtc tac ctg ctt tac gga ttg gtc acc ctc act 31693
Ser Pro Phe Thr Val Tyr Leu Leu Tyr Gly Leu Val Thr Leu Thr
5110 5115 5120
ctc atc tgc agc cta atc aca gta atc atc gcc ttc atc cag tgc 31738
Leu Ile Cys Ser Leu Ile Thr Val Ile Ile Ala Phe Ile Gln Cys
5125 5130 5135
att gat tac atc tgt gtg cgc ctc gca tac ttc aga cac cac ccg 31783
Ile Asp Tyr Ile Cys Val Arg Leu Ala Tyr Phe Arg His His Pro
5140 5145 5150
cag tac cga gac agg aac att gcc caa ctt cta aga ctg ctc taatc 31830
Gln Tyr Arg Asp Arg Asn Ile Ala Gln Leu Leu Arg Leu Leu
5155 5160 5165
atg cat aag act gtg atc tgc ctt ctg atc ctc tgc atc ctg ccc 31875
Met His Lys Thr Val Ile Cys Leu Leu Ile Leu Cys Ile Leu Pro
5170 5175 5180
acc ctc acc tcc tgc cag tac acc aca aaa tct ccg cgc aaa aga 31920
Thr Leu Thr Ser Cys Gln Tyr Thr Thr Lys Ser Pro Arg Lys Arg
5185 5190 5195
cat gcc tcc tgc cgc ttc acc caa ctg tgg aat ata ccc aaa tgc 31965
His Ala Ser Cys Arg Phe Thr Gln Leu Trp Asn Ile Pro Lys Cys
5200 5205 5210
tac aac gaa aag agc gag ctc tcc gaa gct tgg ctg tat ggg gtc 32010
Tyr Asn Glu Lys Ser Glu Leu Ser Glu Ala Trp Leu Tyr Gly Val
5215 5220 5225
atc tgt gtc tta gtt ttc tgc agc act gtc ttt gcc ctc atg atc 32055
Ile Cys Val Leu Val Phe Cys Ser Thr Val Phe Ala Leu Met Ile
5230 5235 5240
tac ccc tac ttt gat ttg gga tgg aac gcg atc gat gcc atg aat 32100
Tyr Pro Tyr Phe Asp Leu Gly Trp Asn Ala Ile Asp Ala Met Asn
5245 5250 5255
tac ccc acc ttt ccc gca ccc gag ata att cca ctg cga caa gtt 32145
Tyr Pro Thr Phe Pro Ala Pro Glu Ile Ile Pro Leu Arg Gln Val
5260 5265 5270
gta ccc gtt gtc gtt aat caa cgc ccc cca tcc cct acg ccc act 32190
Val Pro Val Val Val Asn Gln Arg Pro Pro Ser Pro Thr Pro Thr
5275 5280 5285
gaa atc agc tac ttt aac cta aca ggc gga gat gac tgacgcccta 32236
Glu Ile Ser Tyr Phe Asn Leu Thr Gly Gly Asp Asp
5290 5295 5300
gatctagaaa tggacggcat cagtaccgag cagcgtctcc tagagaggcg caggcaggcg 32296
gctgagcaag agcgcctcaa tcaggagctc cgagatctcg ttaacctgca ccagtgcaaa 32356
agaggcatct tttgtctggt aaagcaggcc aaagtcacct acgagaagac cggcaacagc 32416
caccgcctca gttacaaatt gcccacccag cgccagaagc tggtgctcat ggtgggtgag 32476
aatcccatca ccgtcaccca gcactcggta gagaccgagg ggtgtctgca ctccccctgt 32536
cggggtccag aagacctctg caccctggta aagaccctgt gcggtctcag agatttagtc 32596
ccctttaact aatcaaacac tggaatcaat aaaaagaatc acttacttaa aatcagacag 32656
caggtctctg tccagtttat tcagcagcac ctccttcccc tcctcccaac tctggtactc 32716
caaacgcctt ctggcggcaa acttcctcca caccctgaag gga atg tca gat tct 32771
Met Ser Asp Ser
tgc tcc tgt ccc tcc gca ccc act atc ttc atg ttg ttg cag atg 32816
Cys Ser Cys Pro Ser Ala Pro Thr Ile Phe Met Leu Leu Gln Met
5305 5310 5315
aag cgc acc aaa acg tct gac gag agc ttc aac ccc gtg tac ccc 32861
Lys Arg Thr Lys Thr Ser Asp Glu Ser Phe Asn Pro Val Tyr Pro
5320 5325 5330
tat gac acg gaa agc ggc cct ccc tcc gtc cct ttc ctc acc cct 32906
Tyr Asp Thr Glu Ser Gly Pro Pro Ser Val Pro Phe Leu Thr Pro
5335 5340 5345
ccc ttc gtg tct ccc gat gga ttc caa gaa agt ccc cca ggg gtc 32951
Pro Phe Val Ser Pro Asp Gly Phe Gln Glu Ser Pro Pro Gly Val
5350 5355 5360
ctg tct ctg aac ctg gcc gag ccc ctg gtc act tcc cac ggc atg 32996
Leu Ser Leu Asn Leu Ala Glu Pro Leu Val Thr Ser His Gly Met
5365 5370 5375
ctc gcc ctg aaa atg gga agt ggc ctc tcc ctg gac gac gct ggc 33041
Leu Ala Leu Lys Met Gly Ser Gly Leu Ser Leu Asp Asp Ala Gly
5380 5385 5390
aac ctc acc tct caa gat atc acc acc gct agc cct ccc ctc aaa 33086
Asn Leu Thr Ser Gln Asp Ile Thr Thr Ala Ser Pro Pro Leu Lys
5395 5400 5405
aaa acc aag acc aac ctc agc cta gaa acc tca tcc ccc cta act 33131
Lys Thr Lys Thr Asn Leu Ser Leu Glu Thr Ser Ser Pro Leu Thr
5410 5415 5420
gtg agc acc tca ggc gcc ctc acc gta gca gcc gcc gct ccc ctg 33176
Val Ser Thr Ser Gly Ala Leu Thr Val Ala Ala Ala Ala Pro Leu
5425 5430 5435
gcg gtg gcc ggc acc tcc ctc acc atg caa tca gag gcc ccc ctg 33221
Ala Val Ala Gly Thr Ser Leu Thr Met Gln Ser Glu Ala Pro Leu
5440 5445 5450
aca gta cag gat gca aaa ctc acc ctg gcc acc aaa ggc ccc ctg 33266
Thr Val Gln Asp Ala Lys Leu Thr Leu Ala Thr Lys Gly Pro Leu
5455 5460 5465
acc gtg tct gaa ggc aaa ctg gcc ttg caa aca tcg gcc ccg ctg 33311
Thr Val Ser Glu Gly Lys Leu Ala Leu Gln Thr Ser Ala Pro Leu
5470 5475 5480
acg gcc gct gac agc agc acc ctc aca gtc agt gcc aca cca ccc 33356
Thr Ala Ala Asp Ser Ser Thr Leu Thr Val Ser Ala Thr Pro Pro
5485 5490 5495
ctt agc aca agc aat ggc agc ttg ggt att gac atg caa gcc ccc 33401
Leu Ser Thr Ser Asn Gly Ser Leu Gly Ile Asp Met Gln Ala Pro
5500 5505 5510
att tac acc acc aat gga aaa cta gga ctt aac ttt ggc gct ccc 33446
Ile Tyr Thr Thr Asn Gly Lys Leu Gly Leu Asn Phe Gly Ala Pro
5515 5520 5525
ctg cat gtg gta gac agc cta aat gca ctg act gta gtt act ggc 33491
Leu His Val Val Asp Ser Leu Asn Ala Leu Thr Val Val Thr Gly
5530 5535 5540
caa ggt ctt acg ata aac gga aca gcc cta caa act aga gtc tca 33536
Gln Gly Leu Thr Ile Asn Gly Thr Ala Leu Gln Thr Arg Val Ser
5545 5550 5555
ggt gcc ctc aac tat gac aca tca gga aac cta gaa ttg aga gct 33581
Gly Ala Leu Asn Tyr Asp Thr Ser Gly Asn Leu Glu Leu Arg Ala
5560 5565 5570
gca ggg ggt atg cga gtt gat gca aat ggt caa ctt atc ctt gat 33626
Ala Gly Gly Met Arg Val Asp Ala Asn Gly Gln Leu Ile Leu Asp
5575 5580 5585
gta gct tac cca ttt gat gca caa aac aat ctc agc ctt agg ctt 33671
Val Ala Tyr Pro Phe Asp Ala Gln Asn Asn Leu Ser Leu Arg Leu
5590 5595 5600
gga cag gga ccc ctg ttt gtt aac tct gcc cac aac ttg gat gtt 33716
Gly Gln Gly Pro Leu Phe Val Asn Ser Ala His Asn Leu Asp Val
5605 5610 5615
aac tac aac aga ggc ctc tac ctg ttc aca tct gga aat acc aaa 33761
Asn Tyr Asn Arg Gly Leu Tyr Leu Phe Thr Ser Gly Asn Thr Lys
5620 5625 5630
aag cta gaa gtt aat atc aaa aca gcc aag ggt ctc att tat gat 33806
Lys Leu Glu Val Asn Ile Lys Thr Ala Lys Gly Leu Ile Tyr Asp
5635 5640 5645
gac act gct ata gca atc aat gcg ggt gat ggg cta cag ttt gac 33851
Asp Thr Ala Ile Ala Ile Asn Ala Gly Asp Gly Leu Gln Phe Asp
5650 5655 5660
tca ggc tca gat aca aat cca tta aaa act aaa ctt gga tta gga 33896
Ser Gly Ser Asp Thr Asn Pro Leu Lys Thr Lys Leu Gly Leu Gly
5665 5670 5675
ctg gat tat gac tcc agc aga gcc ata att gct aaa ctg gga act 33941
Leu Asp Tyr Asp Ser Ser Arg Ala Ile Ile Ala Lys Leu Gly Thr
5680 5685 5690
ggc cta agc ttt gac aac aca ggt gcc atc aca gta ggc aac aaa 33986
Gly Leu Ser Phe Asp Asn Thr Gly Ala Ile Thr Val Gly Asn Lys
5695 5700 5705
aat gat gac aag ctc acc ttg tgg acc aca cca gac cca tct cct 34031
Asn Asp Asp Lys Leu Thr Leu Trp Thr Thr Pro Asp Pro Ser Pro
5710 5715 5720
aac tgt aga atc tat tca gag aaa gat gct aaa ttc aca ctt gtt 34076
Asn Cys Arg Ile Tyr Ser Glu Lys Asp Ala Lys Phe Thr Leu Val
5725 5730 5735
ttg act aaa tgc ggc agt cag gtg ttg gcc agc gtt tct gtt tta 34121
Leu Thr Lys Cys Gly Ser Gln Val Leu Ala Ser Val Ser Val Leu
5740 5745 5750
tct gta aaa ggt agc ctt gcg ccc atc agt ggc aca gta act agt 34166
Ser Val Lys Gly Ser Leu Ala Pro Ile Ser Gly Thr Val Thr Ser
5755 5760 5765
gct cag att gtc ctc aga ttt gat gaa aat gga gtt cta cta agc 34211
Ala Gln Ile Val Leu Arg Phe Asp Glu Asn Gly Val Leu Leu Ser
5770 5775 5780
aat tct tcc ctt gac cct caa tac tgg aac tac aga aaa ggt gac 34256
Asn Ser Ser Leu Asp Pro Gln Tyr Trp Asn Tyr Arg Lys Gly Asp
5785 5790 5795
ctt aca gag ggc act gca tat acc aac gca gtg gga ttt atg ccc 34301
Leu Thr Glu Gly Thr Ala Tyr Thr Asn Ala Val Gly Phe Met Pro
5800 5805 5810
aac ctc aca gca tac cca aaa aca cag agc caa act gct aaa agc 34346
Asn Leu Thr Ala Tyr Pro Lys Thr Gln Ser Gln Thr Ala Lys Ser
5815 5820 5825
aac att gta agt cag gtt tac ttg aat ggg gac aaa tcc aaa ccc 34391
Asn Ile Val Ser Gln Val Tyr Leu Asn Gly Asp Lys Ser Lys Pro
5830 5835 5840
atg acc ctc acc att acc ctc aat gga act aat gaa aca gga gat 34436
Met Thr Leu Thr Ile Thr Leu Asn Gly Thr Asn Glu Thr Gly Asp
5845 5850 5855
gcc aca gta agc act tac tcc atg tca ttc tca tgg aac tgg aat 34481
Ala Thr Val Ser Thr Tyr Ser Met Ser Phe Ser Trp Asn Trp Asn
5860 5865 5870
gga agt aat tac att aat gaa acg ttc caa acc aac tcc ttc acc 34526
Gly Ser Asn Tyr Ile Asn Glu Thr Phe Gln Thr Asn Ser Phe Thr
5875 5880 5885
ttc tcc tac atc gcc caa gaa taaaaagcat gacgctgttg atttgattca 34577
Phe Ser Tyr Ile Ala Gln Glu
5890 5895
atgtgtttct gttttatttt caagcacaac aaaatcattc aagtcattct tccatctagc 34637
ttaatataca cagtagctta atagacccag tagtgcaaag ccccattcta gcttataaat 34697
cagacagtga taattaacta ccaccaccat accttttgat tcaggaaatc atgatcatca 34757
caggatccta gtcttcaggc cgccccctcc ctcccaagac acagaataca cagtcctctc 34817
cccccgactg gctttaaata acaccatctg gttggtcaca gacatgttct taggggttat 34877
attccacacg gtctcctgcc gcgccaggcg ctcgtcggtg atgttgataa actctcccgg 34937
cagctcgctc aagttcacgt cgctgtccag cggctgaacc tccggctgac gcgataactg 34997
tgcgaccggc tgctggacaa acggaggccg cgcctacaag ggggtagagt cataatcctc 35057
ggtcaggata gggcggtgat gcagcagcag cgagcgaaac atctgctgcc gccgccgctc 35117
cgtccggcag gaaaacaaca cgccggtggt ctcctccgcg ataatccgca ccgcccgcag 35177
catcagcttc ctcgttctcc gcgcgcagca cctcaccctg atctcgctca agtcggcgca 35237
gtaggtacag cacagcacca cgatgttatt catgatccca cagtgcaggg cgctgtatcc 35297
aaagctcatg ccgggaacca ccgcccccac gtggccatcg taccacaagc gcacgtaaat 35357
taagtgtcga cccctcatga acgtgctgga cacaaacatt acttccttgg gcatgttgta 35417
attcaccacc tcccggtacc agataaacct ctggttaaac agggcacctt ccaccaccat 35477
cctgaaccaa gaggccagaa cctgcccacc ggctatgcac tgcagggaac ccgggttgga 35537
acaatgacaa tgcagactcc aaggctcgta accgtggatc atccggctgc tgaaggcatc 35597
gatgttggca caacacagac acacgtgcat gcactttctc atgattagca gctcttccct 35657
cgtcaggatc atatcccaag gaataaccca ttcttgaatc aacgtaaaac ccacacagca 35717
gggaaggcct cgcacataac tcacgttgtg catggtcagc gtgttgcatt ccggaaacag 35777
cggatgatcc tccagtatcg aggcgcgggt ctccttctca cagggaggta aagggtccct 35837
gctgtacgga ctgcgccggg acgaccgaga tcgtgttgag cgtagtgtca tggaaaaggg 35897
aacgccggac gtggtcatac ttcttgaagc agaaccaggt tcgcgcgtgg caggcctcct 35957
tgcgtctgcg gtctcgccgt ctagctcgct ccgtgtgata gttgtagtac agccactccc 36017
gcagagcgtc gaggcgcacc ctggcttccg gatctatgta gactccgtct tgcaccgcgg 36077
ccctgataat atccaccacc gtagaataag caacacccag ccaagcaata cactcgctct 36137
gcgagcggca gacaggagga gcgggcagag atgggagaac catgataaaa aacttttttt 36197
taaagaatat tttccaattc ttcgaaagta agatctatca agtggcagcg ctcccctcca 36257
ctggcgcggt caaactctac ggccaaagca cagacaacgg catttctaag atgttcctta 36317
atggcgtcca aaagacacac cgctctcaag ttgcagtaaa ctatgaatga aaacccatcc 36377
ggctgatttt ccaatataga cgcgccggcg gcgtccacca aacccagata attttcttct 36437
ctccagcggt ttagaatctg tctaagcaaa tcccttatat caagtccggc catgccaaaa 36497
atctgctcaa gagcgccctc caccttcatg accaagcagc gcatcatgat tgcaaaaatt 36557
caggttcttc agagacctgt ataagattca aaatgggaac attaacaaaa attcctctgt 36617
cgcgcagatc ccttcgcagg gcaagctgaa cataatcaga caggtctgaa cggaccagtg 36677
aggccaaatc cccaccagga accagatcca gagaccctat actgattatg acgcgcatac 36737
tcggggctat gctgaccagc gtagcgccga tgtaggcgtg ctgcatgggc ggcgagataa 36797
aatgcaaagt gctggttaaa aaatcaggca aagcctcgcg caaaaaagct aacacatcat 36857
aatcatgctc atgcaggtag ttgcaggtaa gctcaggaac caaaacggaa taacacacga 36917
ttttcctctc aaacatgact tcgcggatac tgcgtaaaac aaaaattata aataaaaaat 36977
taattaactt aaacattgga agcctgtctc acaacaggaa aaaccacttt aatcaacata 37037
agacgggcca cgggcatgcc ggcatagccg taaaaaaatt ggtccccgtg attaacaagt 37097
accacagaca gctccccggt catgtcgggg gtcatcatgt gagactctgt atacacgtct 37157
ggattgtgaa catcagacaa acaaagaaat cgagccacgt agcccggagg tataatcacc 37217
cgcaggcgga ggtacagcaa aacgaccccc ataggaggaa tcacaaaatt agtaggagaa 37277
aaaaatacat aaacaccaga aaaaccctgt tgctgaggca aaatagcgcc ctcccgatcc 37337
aaaacaacat aaagcgcttc cacaggagca gccataacaa agacccgagt cttaccagta 37397
aaagaaaaaa gatctctcaa cgcagcacca gcaccaacac ttcgcagtgt aaaaggccaa 37457
gtgccgagag agtatatata ggaataaaaa gtgacgtaaa cgggcaaagt ccaaaaaacg 37517
cccagaaaaa ccgcacgcga acctacgccc cgaaacgaaa gccaaaaaac actagacact 37577
cccttccggc gtcaacttcc ggtttcccac gctacgtcac ttcccccagt caaacaaact 37637
acatatcccg aacttccaag tcgccacgcc caaaacaccg cctacacctc cccgcccgcc 37697
ggcccgcccc caaacccgcc tcccgccccg cgccccgccc cgcgccgccc atctcattat 37757
catattggct tcaatccaaa ataaggtata ttattgatga tg 37799
<210> 64
<211> 212
<212> PRT
<213> Simian adenovirus 34
<400> 64
Met Val Cys Leu Thr Trp Ala Glu Ser Ala Gly Tyr Ile Ser Phe Pro
1 5 10 15
Gly Leu Asn Leu Val Thr Leu Asp Leu Met Glu Ala Trp Glu Cys Leu
20 25 30
Glu Asn Phe Ala Gly Val Arg Ala Leu Leu Asp Glu Ser Ser Asn Asn
35 40 45
Thr Ser Trp Trp Trp Arg Tyr Leu Trp Gly Ser Pro Gln Gly Lys Leu
50 55 60
Val Cys Arg Ile Lys Glu Asp Tyr Lys Trp Glu Phe Glu Glu Leu Leu
65 70 75 80
Lys Ser Cys Gly Glu Leu Leu Asp Ser Leu Asn Leu Gly His Gln Ala
85 90 95
Leu Phe Gln Glu Lys Val Ile Arg Thr Leu Asp Phe Ser Thr Pro Gly
100 105 110
Arg Ile Ala Ala Ala Val Ala Phe Leu Ala Phe Leu Lys Asp Arg Trp
115 120 125
Ser Glu Glu Thr His Leu Ser Ser Gly Tyr Val Leu Asp Phe Leu Ala
130 135 140
Met Gln Leu Trp Arg Ala Trp Ile Arg His Lys Asn Arg Leu Gln Leu
145 150 155 160
Leu Ser Ser Val Arg Pro Leu Leu Ile Pro Ala Glu Glu Gln Gln Ala
165 170 175
Gly Ser Glu Asp Arg Ala Arg Arg Asp Pro Glu Glu Arg Ala Pro Arg
180 185 190
Pro Gly Glu Arg Ser Ala Pro Asn Leu Gly Thr Gly Leu Ser Gly His
195 200 205
Pro His Arg Glu
210
<210> 65
<211> 155
<212> PRT
<213> Simian adenovirus 34
<400> 65
Met Ser Gly Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ala Leu Asp
1 5 10 15
Gly Ser Ile Val Ser Pro Tyr Leu Thr Thr Arg Met Pro His Trp Ala
20 25 30
Gly Val Arg Gln Asn Val Met Gly Ser Ser Ile Asp Gly Arg Pro Val
35 40 45
Leu Pro Ala Asn Ser Ala Thr Leu Thr Tyr Ala Thr Val Ala Gly Thr
50 55 60
Pro Leu Asp Ala Thr Ala Ala Ala Ala Ala Thr Ala Ala Ala Ser Ala
65 70 75 80
Val Arg Ser Leu Ala Thr Asp Phe Ala Phe Leu Gly Pro Leu Ala Thr
85 90 95
Gly Ala Thr Ser Arg Ala Ala Ala Ala Ala Val Arg Asp Asp Lys Leu
100 105 110
Thr Ala Leu Leu Ala Gln Leu Asp Ala Leu Thr Arg Glu Leu Gly Asp
115 120 125
Leu Ser Gln Gln Val Met Ala Leu Arg Gln Gln Val Ser Ser Leu Gln
130 135 140
Ala Gly Gly Asn Ala Ser Pro Thr Asn Ala Val
145 150 155
<210> 66
<211> 419
<212> PRT
<213> Simian adenovirus 34
<400> 66
Met His Pro Val Leu Arg Gln Met Arg Pro Pro Pro Gln Gln Gln Gln
1 5 10 15
Gln His Gln Gln Glu Arg Gln Gln Gln Gln Arg Glu Ser Cys Arg Ala
20 25 30
Pro Ser Pro Thr Leu Gly Gly Pro Ala Thr Ser Ala Ser Ala Ala Val
35 40 45
Ser Gly Ala Cys Gly Gly Gly Gly Gly Pro Ala Asp Asp Pro Glu Glu
50 55 60
Pro Pro Arg Arg Arg Ala Arg His Tyr Leu Asp Leu Glu Glu Gly Glu
65 70 75 80
Gly Leu Ala Arg Leu Gly Ala Pro Ser Pro Glu Arg His Pro Arg Val
85 90 95
Gln Leu Lys Arg Asp Ser Arg Glu Ala Tyr Val Pro Arg Gln Asn Leu
100 105 110
Phe Arg Asp Arg Ala Gly Glu Glu Pro Glu Glu Met Arg Asp Arg Arg
115 120 125
Phe Ser Ala Gly Arg Glu Leu Arg Gln Gly Leu Asn Arg Glu Arg Leu
130 135 140
Leu Arg Glu Glu Asp Phe Glu Pro Asp Ala Arg Thr Gly Ile Ser Pro
145 150 155 160
Ala Arg Ala His Val Ala Ala Ala Asp Leu Val Thr Ala Tyr Glu Gln
165 170 175
Thr Val Asn Gln Glu Ile Asn Phe Gln Lys Ser Phe Asn Asn His Val
180 185 190
Arg Thr Leu Val Ala Arg Glu Glu Val Thr Ile Gly Leu Met His Leu
195 200 205
Trp Asp Phe Val Ser Ala Leu Val Gln Asn Pro Asn Ser Lys Pro Leu
210 215 220
Thr Ala Gln Leu Phe Leu Ile Val Gln His Ser Arg Asp Asn Glu Ala
225 230 235 240
Phe Arg Asp Ala Leu Leu Asn Ile Thr Glu Pro Glu Gly Arg Trp Leu
245 250 255
Leu Asp Leu Ile Asn Ile Leu Gln Ser Ile Val Val Gln Glu Arg Ser
260 265 270
Leu Ser Leu Ala Asp Lys Val Ala Ala Ile Asn Tyr Ser Met Leu Ser
275 280 285
Leu Gly Lys Phe Tyr Ala Arg Lys Ile Tyr Gln Thr Pro Tyr Val Pro
290 295 300
Ile Asp Lys Glu Val Lys Ile Asp Gly Phe Tyr Met Arg Met Ala Leu
305 310 315 320
Lys Val Leu Thr Leu Ser Asp Asp Leu Gly Val Tyr Arg Asn Glu Arg
325 330 335
Ile His Lys Ala Val Ser Val Ser Arg Arg Arg Glu Leu Ser Asp Arg
340 345 350
Glu Leu Met His Ser Leu Gln Arg Ala Leu Ala Gly Ala Gly Ser Gly
355 360 365
Asp Arg Glu Val Glu Ser Tyr Phe Asp Ala Gly Ala Asp Leu Arg Trp
370 375 380
Ala Pro Ser Arg Arg Ala Leu Glu Ala Ala Gly Val Arg Glu Asp Tyr
385 390 395 400
Asp Glu Asp Gly Glu Glu Asp Glu Glu Tyr Glu Leu Glu Glu Gly Glu
405 410 415
Tyr Leu Asp
<210> 67
<211> 592
<212> PRT
<213> Simian adenovirus 34
<400> 67
Met Gln Asp Pro Asn Val Val Asp Pro Ala Leu Arg Ala Ala Leu Gln
1 5 10 15
Ser Gln Pro Ser Gly Leu Asn Ser Ser Asp Asp Trp Arg Gln Val Met
20 25 30
Asp Arg Ile Met Ser Leu Thr Ala Arg Asn Pro Asp Ala Phe Arg Gln
35 40 45
Gln Pro Gln Ala Asn Arg Leu Ser Ala Ile Leu Glu Ala Val Val Pro
50 55 60
Ala Arg Ser Asn Pro Thr His Glu Lys Val Leu Ala Ile Val Asn Ala
65 70 75 80
Leu Ala Glu Asn Arg Ala Ile Arg Pro Asp Glu Ala Gly Leu Val Tyr
85 90 95
Asp Ala Leu Leu Gln Arg Val Ala Arg Tyr Asn Ser Gly Asn Val Gln
100 105 110
Thr Asn Leu Asp Arg Leu Val Gly Asp Val Arg Glu Ala Val Ala Gln
115 120 125
Arg Glu Arg Ala Asp Arg Gln Gly Asn Leu Gly Ser Met Val Ala Leu
130 135 140
Asn Ala Phe Leu Ser Thr Gln Pro Ala Asn Val Pro Arg Gly Gln Glu
145 150 155 160
Asp Tyr Thr Asn Phe Val Ser Ala Leu Arg Leu Met Val Thr Glu Thr
165 170 175
Pro Gln Ser Glu Val Tyr Gln Ser Gly Pro Asp Tyr Phe Phe Gln Thr
180 185 190
Ser Arg Gln Gly Leu Gln Thr Val Asn Leu Ser Gln Ala Phe Lys Asn
195 200 205
Leu Arg Gly Leu Trp Gly Val Lys Ala Pro Thr Gly Asp Arg Ala Thr
210 215 220
Val Ser Ser Leu Leu Thr Pro Asn Ser Arg Leu Leu Leu Leu Leu Ile
225 230 235 240
Ala Pro Phe Thr Asp Ser Gly Ser Val Ser Arg Asp Thr Tyr Leu Gly
245 250 255
His Leu Leu Thr Leu Tyr Arg Glu Ala Ile Gly Gln Ala Gln Val Asp
260 265 270
Glu His Thr Phe Gln Glu Ile Thr Ser Val Ser Arg Ala Leu Gly Gln
275 280 285
Glu Asp Thr Ser Ser Leu Glu Ala Thr Leu Asn Tyr Leu Leu Thr Asn
290 295 300
Arg Arg Gln Lys Ile Pro Ser Leu His Ser Leu Thr Ser Glu Glu Glu
305 310 315 320
Arg Ile Leu Arg Tyr Val Gln Gln Ser Val Ser Leu Asn Leu Met Arg
325 330 335
Asp Gly Val Thr Pro Ser Val Ala Leu Asp Met Thr Ala Arg Asn Met
340 345 350
Glu Pro Gly Met Tyr Ala Ala His Arg Pro Tyr Ile Asn Arg Leu Met
355 360 365
Asp Tyr Leu His Arg Ala Ala Ala Val Asn Pro Glu Tyr Phe Thr Asn
370 375 380
Ala Ile Leu Asn Pro His Trp Leu Pro Pro Pro Gly Phe Tyr Ser Gly
385 390 395 400
Gly Phe Glu Val Pro Glu Ala Asn Asp Gly Phe Leu Trp Asp Asp Met
405 410 415
Asp Asp Ser Val Phe Ser Pro Arg Pro Gln Ala Leu Ala Glu Ala Ser
420 425 430
Leu Leu Arg Pro Lys Lys Glu Glu Glu Ala Ser Arg Arg Arg Arg Gly
435 440 445
Ser Ser Gly Val Ala Ser Leu Ser Glu Leu Gly Ala Ala Ala Ala Ala
450 455 460
Arg Pro Gly Ser Leu Gly Gly Ser Pro Phe Pro Ser Leu Val Gly Ser
465 470 475 480
Leu His Ser Glu Arg Thr Thr Arg Pro Arg Leu Leu Gly Glu Asp Glu
485 490 495
Tyr Leu Asn Asn Ser Leu Leu Gln Pro Val Arg Glu Lys Asn Leu Pro
500 505 510
Pro Ala Phe Pro Asn Asn Gly Ile Glu Ser Leu Val Asp Lys Met Ser
515 520 525
Arg Trp Lys Thr Tyr Ala Gln Glu His Arg Asp Ala Pro Ala Leu Arg
530 535 540
Pro Pro Thr Arg Arg Gln Arg His Asp Arg Gln Arg Gly Leu Val Trp
545 550 555 560
Asp Asp Glu Asp Ser Ala Asp Asp Ser Ser Val Leu Asp Leu Gly Gly
565 570 575
Ser Gly Asn Pro Phe Ala His Leu Arg Pro Arg Leu Gly Arg Met Phe
580 585 590
<210> 68
<211> 617
<212> PRT
<213> Simian adenovirus 34
<400> 68
Met Met Gln Lys Leu Asn Lys Thr His Gln Gly His Gly Asp Arg Ala
1 5 10 15
Leu Val Ser Cys Val Pro Phe Ser Met Arg Arg Ala Ala Met Tyr Gln
20 25 30
Glu Gly Pro Pro Pro Ser Tyr Glu Ser Val Val Gly Ala Ala Ala Ala
35 40 45
Ala Pro Ser Ser Pro Phe Ala Ser Gln Leu Leu Glu Pro Pro Tyr Val
50 55 60
Pro Pro Arg Tyr Leu Arg Pro Thr Gly Gly Arg Asn Ser Ile Arg Tyr
65 70 75 80
Ser Glu Leu Ala Pro Leu Phe Asp Thr Thr Arg Val Tyr Leu Val Asp
85 90 95
Asn Lys Ser Ala Asp Val Ala Ser Leu Asn Tyr Gln Asn Asp His Ser
100 105 110
Asn Phe Leu Thr Thr Val Ile Gln Asn Asn Asp Tyr Ser Pro Ser Glu
115 120 125
Ala Ser Thr Gln Thr Ile Asn Leu Asp Asp Arg Ser His Trp Gly Gly
130 135 140
Asp Leu Lys Thr Ile Leu His Thr Asn Met Pro Asn Val Asn Glu Phe
145 150 155 160
Met Phe Thr Asn Lys Phe Lys Ala Arg Val Met Val Ser Arg Ser His
165 170 175
Thr Lys Glu Asp Arg Val Glu Leu Lys Tyr Glu Trp Val Glu Phe Glu
180 185 190
Leu Pro Glu Gly Asn Tyr Ser Glu Thr Met Thr Ile Asp Leu Met Asn
195 200 205
Asn Ala Ile Val Glu His Tyr Leu Lys Val Gly Arg Gln Asn Gly Val
210 215 220
Leu Glu Ser Asp Ile Gly Val Lys Phe Asp Thr Arg Asn Phe Arg Leu
225 230 235 240
Gly Leu Asp Pro Val Thr Gly Leu Val Met Pro Gly Val Tyr Thr Asn
245 250 255
Glu Ala Phe His Pro Asp Ile Ile Leu Leu Pro Gly Cys Gly Val Asp
260 265 270
Phe Thr Tyr Ser Arg Leu Ser Asn Leu Leu Gly Ile Arg Lys Arg Gln
275 280 285
Pro Phe Gln Glu Gly Phe Arg Ile Thr Tyr Glu Asp Leu Glu Gly Gly
290 295 300
Asn Ile Pro Ala Leu Leu Asp Val Glu Ala Tyr Gln Asp Ser Leu Lys
305 310 315 320
Glu Asn Glu Ala Gly Gln Glu Asp Thr Ala Pro Ala Ala Ser Ala Ala
325 330 335
Ala Glu Gln Gly Glu Asp Ala Ala Asp Thr Ala Ala Ala Asp Gly Ala
340 345 350
Glu Ala Asp Pro Ala Met Val Val Glu Ala Ala Glu Gln Glu Glu Asp
355 360 365
Met Asn Asp Ser Ala Val Arg Gly Asp Thr Phe Val Thr Arg Gly Glu
370 375 380
Glu Lys Gln Ala Glu Ala Glu Ala Ala Ala Glu Glu Lys Gln Leu Ala
385 390 395 400
Ala Ala Ala Ala Ala Ala Ala Leu Ala Ala Ala Glu Ala Glu Ser Glu
405 410 415
Gly Thr Lys Pro Ala Lys Glu Pro Val Ile Lys Pro Leu Thr Glu Asp
420 425 430
Ser Lys Lys Arg Ser Tyr Asn Leu Leu Lys Asp Ser Thr Asn Thr Ala
435 440 445
Tyr Arg Ser Trp Tyr Leu Ala Tyr Asn Tyr Gly Asp Pro Ser Thr Gly
450 455 460
Val Arg Ser Trp Thr Leu Leu Cys Thr Pro Asp Val Thr Cys Gly Ser
465 470 475 480
Glu Gln Val Tyr Trp Ser Leu Pro Asp Met Met Gln Asp Pro Val Thr
485 490 495
Phe Arg Ser Thr Arg Gln Val Ser Asn Phe Pro Val Val Gly Ala Glu
500 505 510
Leu Leu Pro Val His Ser Lys Ser Phe Tyr Asn Asp Gln Ala Val Tyr
515 520 525
Ser Gln Leu Ile Arg Gln Phe Thr Ser Leu Thr His Val Phe Asn Arg
530 535 540
Phe Pro Glu Asn Gln Ile Leu Ala Arg Pro Pro Ala Pro Thr Ile Thr
545 550 555 560
Thr Val Ser Glu Asn Val Pro Ala Leu Thr Asp His Gly Thr Leu Pro
565 570 575
Leu Arg Asn Ser Ile Gly Gly Val Gln Arg Val Thr Val Thr Asp Ala
580 585 590
Arg Arg Arg Thr Cys Pro Tyr Val Tyr Lys Ala Leu Gly Ile Val Ser
595 600 605
Pro Arg Val Leu Ser Ser Arg Thr Phe
610 615
<210> 69
<211> 198
<212> PRT
<213> Simian adenovirus 34
<400> 69
Met Ser Ile Leu Ile Ser Pro Ser Asn Asn Ser Gly Trp Gly Leu Leu
1 5 10 15
Arg Ala Pro Ser Lys Met Phe Gly Gly Ala Arg Lys Arg Ser Glu Gln
20 25 30
His Pro Val Arg Val Arg Gly His Phe Arg Ala Pro Trp Gly Ala His
35 40 45
Lys Arg Gly Arg Ala Gly Arg Thr Thr Val Asp Asp Ala Ile Asp Ser
50 55 60
Val Val Glu Gln Ala Arg Asn Tyr Arg Pro Ala Val Ser Thr Val Asp
65 70 75 80
Ala Ala Ile Gln Thr Val Val Arg Gly Ala Arg Arg Tyr Ala Lys Leu
85 90 95
Lys Ser Arg Arg Lys Arg Val Ala Arg Arg His Arg Arg Arg Pro Gly
100 105 110
Ala Ala Ala Lys Arg Ala Ala Ala Ala Leu Leu Arg Arg Ala Lys Arg
115 120 125
Thr Gly Arg Arg Ala Ala Met Arg Ala Ala Arg Arg Leu Ala Ala Gly
130 135 140
Ile Thr Ala Ala Thr Met Ala Pro Arg Thr Arg Arg Arg Ala Ala Ala
145 150 155 160
Ala Ala Ala Ala Ala Ile Ser Asp Met Ala Ser Arg Arg Arg Gly Asn
165 170 175
Val Tyr Trp Val Arg Asp Ser Val Thr Gly Thr Arg Val Pro Val Arg
180 185 190
Phe Arg Pro Pro Arg Thr
195
<210> 70
<211> 371
<212> PRT
<213> Simian adenovirus 34
<400> 70
Met Ser Lys Arg Lys Ile Lys Glu Glu Met Leu Gln Val Val Ala Pro
1 5 10 15
Glu Ile Tyr Gly Pro Pro Lys Lys Glu Glu Gln Asp Ser Lys Pro Arg
20 25 30
Lys Ile Lys Arg Val Lys Lys Lys Lys Lys Asp Asp Asp Asp Ala Asp
35 40 45
Gly Glu Val Glu Phe Leu Arg Ala Thr Ala Pro Arg Arg Pro Val Gln
50 55 60
Trp Lys Gly Arg Arg Val Lys Arg Val Leu Arg Pro Gly Thr Ala Val
65 70 75 80
Val Phe Thr Pro Gly Glu Arg Ser Thr Arg Thr Phe Lys Arg Val Tyr
85 90 95
Asp Glu Val Tyr Gly Asp Glu Asp Leu Leu Glu Gln Ala Asn Glu Arg
100 105 110
Phe Gly Glu Phe Ala Tyr Gly Lys Arg Gln Arg Ala Leu Gly Lys Glu
115 120 125
Asp Leu Leu Ala Leu Pro Leu Asp Gln Gly Asn Pro Thr Pro Ser Leu
130 135 140
Lys Pro Val Thr Leu Gln Gln Val Leu Pro Ser Ser Ala Pro Ser Glu
145 150 155 160
Ala Lys Arg Gly Leu Lys Arg Glu Gly Gly Asp Leu Ala Pro Thr Val
165 170 175
Gln Leu Met Val Pro Lys Arg Gln Arg Leu Glu Asp Val Leu Glu Lys
180 185 190
Met Lys Val Asp Pro Gly Leu Gln Pro Asp Ile Arg Val Arg Pro Ile
195 200 205
Lys Gln Val Ala Pro Gly Leu Gly Val Gln Thr Val Asp Val Val Ile
210 215 220
Pro Thr Gly Asn Ser Pro Ala Ala Ala Thr Thr Thr Ala Ala Ser Thr
225 230 235 240
Asp Met Glu Thr Gln Thr Asp Pro Ala Ala Ala Ala Ala Ala Ala Ala
245 250 255
Ala Ala Thr Ser Ser Ala Glu Val Gln Thr Asp Pro Trp Leu Pro Pro
260 265 270
Ala Met Ser Ala Pro Arg Ala Arg Arg Gly Arg Arg Lys Tyr Gly Ala
275 280 285
Ala Asn Ala Leu Leu Pro Glu Tyr Ala Leu His Pro Ser Ile Ala Pro
290 295 300
Thr Pro Gly Tyr Arg Gly Tyr Thr Tyr Arg Pro Arg Arg Ala Lys Gly
305 310 315 320
Ser Thr Arg Arg Pro Arg Arg Arg Ala Ala Ala Thr Thr Arg Arg Arg
325 330 335
Arg Arg Arg Arg Gln Pro Ala Leu Ala Pro Val Ser Val Arg Arg Val
340 345 350
Ala Arg Asp Gly His Thr Leu Val Leu Pro Arg Ala Arg Tyr His Pro
355 360 365
Ser Ile Val
370
<210> 71
<211> 81
<212> PRT
<213> Simian adenovirus 34
<400> 71
Met Ala Leu Thr Cys Arg Leu Arg Phe Pro Val Pro Gly Tyr Arg Gly
1 5 10 15
Gly Arg Ser Arg Arg Arg Arg Gly Leu Ala Gly Arg Gly Leu Ser Gly
20 25 30
Gly Ser Arg Arg Ala His Arg Arg Arg Arg Ala Thr Ser Arg Arg Met
35 40 45
Arg Gly Gly Val Leu Pro Leu Leu Ile Pro Leu Ile Ala Ala Ala Ile
50 55 60
Gly Ala Val Pro Gly Ile Ala Ser Val Ala Leu Gln Ala Ser Gln Arg
65 70 75 80
His
<210> 72
<211> 251
<212> PRT
<213> Simian adenovirus 34
<400> 72
Met Glu Asp Ile Asn Phe Ala Ser Leu Ala Pro Arg His Gly Ser Arg
1 5 10 15
Pro Phe Leu Gly His Trp Asn Asp Ile Gly Thr Ser Asn Met Ser Gly
20 25 30
Gly Ala Phe Ser Trp Gly Ser Leu Trp Ser Gly Ile Lys Ser Ile Gly
35 40 45
Ser Ala Val Lys Asn Tyr Gly Ser Arg Ala Trp Asn Ser Ser Thr Gly
50 55 60
Gln Met Leu Arg Asp Lys Leu Lys Glu Gln Asn Phe Gln Gln Lys Val
65 70 75 80
Val Glu Gly Leu Ala Ser Gly Ile Asn Gly Val Val Asp Leu Ala Asn
85 90 95
Gln Ala Val Gln Asn Lys Ile Asn Ser Arg Leu Asp Pro Arg Pro Pro
100 105 110
Val Glu Glu Val Pro Pro Ala Leu Glu Thr Val Ser Pro Asp Gly Arg
115 120 125
Gly Glu Lys Arg Pro Arg Pro Asp Arg Glu Glu Thr Thr Leu Val Thr
130 135 140
Gln Thr Asp Glu Pro Pro Pro Tyr Glu Glu Ala Leu Lys Gln Gly Leu
145 150 155 160
Pro Thr Thr Arg Pro Ile Ala Pro Met Ala Thr Gly Val Val Gly Arg
165 170 175
His Thr Pro Ala Thr Leu Asp Leu Pro Pro Pro Ala Asp Val Pro Gln
180 185 190
Gln Gln Lys Ala Ala Gln Pro Gly Pro Pro Ala Thr Ala Ser Arg Ser
195 200 205
Ser Ala Gly Pro Leu Arg Arg Ala Ala Ser Gly Pro Arg Gly Gly Val
210 215 220
Ala Arg His Gly Asn Trp Gln Ser Thr Leu Asn Ser Ile Val Gly Leu
225 230 235 240
Gly Val Arg Ser Val Lys Arg Arg Arg Cys Tyr
245 250
<210> 73
<211> 958
<212> PRT
<213> Simian adenovirus 34
<400> 73
Met Ala Thr Pro Ser Met Met Pro Gln Trp Ser Tyr Met His Ile Ser
1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30
Arg Ala Thr Glu Ser Tyr Phe Ser Leu Ser Asn Lys Phe Arg Asn Pro
35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu
50 55 60
Thr Leu Arg Phe Ile Pro Val Asp Arg Glu Asp Thr Ala Tyr Ser Tyr
65 70 75 80
Lys Ala Arg Phe Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95
Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Thr
100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Ser Leu Ala Pro Lys Gly
115 120 125
Ala Pro Asn Ser Cys Glu Trp Glu Gln Leu Glu Glu Ala Gln Ala Ala
130 135 140
Val Glu Asp Glu Glu Leu Glu Asp Glu Asp Glu Glu Pro Gln Asp Glu
145 150 155 160
Ala Pro Val Lys Lys Thr His Val Tyr Ala Gln Ala Pro Leu Ser Gly
165 170 175
Glu Glu Ile Thr Lys Asn Gly Leu Gln Ile Gly Ser Asp Asn Thr Glu
180 185 190
Ala Gln Ser Lys Pro Ile Tyr Ala Asp Pro Thr Phe Gln Pro Glu Pro
195 200 205
Gln Ile Gly Glu Ser Gln Trp Asn Glu Ala Asp Ala Thr Val Ala Gly
210 215 220
Gly Arg Val Leu Lys Lys Ser Thr Pro Met Lys Pro Cys Tyr Gly Ser
225 230 235 240
Tyr Ala Arg Pro Thr Asn Ser Asn Gly Gly Gln Gly Val Leu Val Ala
245 250 255
Asp Asp Lys Gly Val Leu Gln Ser Lys Val Glu Leu Gln Phe Phe Ser
260 265 270
Asn Thr Thr Thr Leu Asn Gln Arg Glu Gly Asn Asp Thr Lys Pro Lys
275 280 285
Val Val Leu Tyr Ser Glu Asp Val His Met Glu Thr Pro Asp Thr His
290 295 300
Ile Ser Tyr Lys Pro Thr Lys Ser Asp Asp Asn Ser Lys Ile Met Leu
305 310 315 320
Gly Gln Gln Ser Met Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp
325 330 335
Asn Phe Ile Gly Leu Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val
340 345 350
Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val Asp Leu Gln Asp
355 360 365
Arg Asn Thr Glu Leu Ser Tyr Gln Leu Leu Leu Asp Ser Met Gly Asp
370 375 380
Arg Thr Arg Tyr Phe Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp
385 390 395 400
Pro Asp Val Arg Ile Ile Glu Asn His Gly Thr Glu Asp Glu Leu Pro
405 410 415
Asn Tyr Cys Phe Pro Leu Gly Gly Ile Gly Val Thr Asp Thr Tyr Gln
420 425 430
Ala Ile Lys Thr Asn Gly Asn Gly Gln Glu Asn Pro Thr Trp Glu Lys
435 440 445
Asp Thr Glu Phe Ala Asp Arg Asn Glu Ile Gly Val Gly Asn Asn Phe
450 455 460
Ala Met Glu Ile Asn Leu Ser Ala Asn Leu Trp Arg Asn Phe Leu Tyr
465 470 475 480
Ser Asn Val Ala Leu Tyr Leu Pro Asp Lys Leu Lys Tyr Asn Pro Ser
485 490 495
Asn Val Asp Ile Ser Asp Asn Pro Asn Thr Tyr Asp Tyr Met Asn Lys
500 505 510
Arg Val Val Ala Pro Gly Leu Val Asp Cys Tyr Ile Asn Leu Gly Ala
515 520 525
Arg Trp Ser Leu Asp Tyr Met Asp Asn Val Asn Pro Phe Asn His His
530 535 540
Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly Arg
545 550 555 560
Tyr Val Pro Phe His Ile Gln Val Pro Gln Lys Phe Phe Ala Ile Lys
565 570 575
Asn Leu Leu Leu Leu Pro Gly Ser Tyr Thr Tyr Glu Trp Asn Phe Arg
580 585 590
Lys Asp Val Asn Met Val Leu Gln Ser Ser Leu Gly Asn Asp Leu Arg
595 600 605
Val Asp Gly Ala Ser Ile Lys Phe Glu Ser Ile Cys Leu Tyr Ala Thr
610 615 620
Phe Phe Pro Met Ala His Asn Thr Ala Ser Thr Leu Glu Ala Met Leu
625 630 635 640
Arg Asn Asp Thr Asn Asp Gln Ser Phe Asn Asp Tyr Leu Ser Ala Ala
645 650 655
Asn Met Leu Tyr Pro Ile Pro Ala Asn Ala Thr Asn Val Pro Ile Ser
660 665 670
Ile Pro Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ala Phe Thr Arg
675 680 685
Leu Lys Thr Lys Glu Thr Pro Ser Leu Gly Ser Gly Phe Asp Pro Tyr
690 695 700
Tyr Thr Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly Thr Phe Tyr Leu
705 710 715 720
Asn His Thr Phe Lys Lys Val Ser Val Thr Phe Asp Ser Ser Val Ser
725 730 735
Trp Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile Lys
740 745 750
Arg Ser Val Asp Gly Glu Gly Tyr Asn Val Ala Gln Cys Asn Met Thr
755 760 765
Lys Asp Trp Phe Leu Val Gln Met Leu Ala Asn Tyr Asn Ile Gly Tyr
770 775 780
Gln Gly Phe Tyr Ile Pro Glu Ser Tyr Lys Asp Arg Met Tyr Ser Phe
785 790 795 800
Phe Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val Asp Gln Thr Lys
805 810 815
Tyr Lys Asp Tyr Gln Glu Val Gly Ile Ile His Gln His Asn Asn Ser
820 825 830
Gly Phe Val Gly Tyr Leu Ala Pro Thr Met Arg Glu Gly Gln Ala Tyr
835 840 845
Pro Ala Asn Phe Pro Tyr Pro Leu Ile Gly Lys Thr Ala Val Asp Ser
850 855 860
Ile Thr Gln Lys Lys Phe Leu Cys Asp Arg Thr Leu Trp Arg Ile Pro
865 870 875 880
Phe Ser Ser Asn Phe Met Ser Met Gly Ala Leu Ser Asp Leu Gly Gln
885 890 895
Asn Leu Leu Tyr Ala Asn Ser Ala His Ala Leu Asp Met Thr Phe Glu
900 905 910
Val Asp Pro Met Asp Glu Pro Thr Leu Leu Tyr Val Leu Phe Glu Val
915 920 925
Phe Asp Val Val Arg Val His Gln Pro His Arg Gly Val Ile Glu Thr
930 935 940
Val Tyr Leu Arg Thr Pro Phe Ser Ala Gly Asn Ala Thr Thr
945 950 955
<210> 74
<211> 209
<212> PRT
<213> Simian adenovirus 34
<400> 74
Met Pro Ser Gly Ser Thr Glu Gln Glu Leu Arg Ala Ile Val Arg Asp
1 5 10 15
Leu Gly Cys Gly Pro Tyr Phe Leu Gly Thr Phe Asp Lys Arg Phe Pro
20 25 30
Gly Phe Val Ser Pro His Lys Leu Ala Cys Ala Ile Val Asn Thr Ala
35 40 45
Gly Arg Glu Thr Gly Gly Val His Trp Leu Ala Phe Ala Trp Asn Pro
50 55 60
Arg Ser Lys Thr Cys Phe Leu Phe Asp Pro Phe Gly Phe Ser Asp Gln
65 70 75 80
Arg Leu Lys Gln Ile Tyr Glu Phe Glu Tyr Glu Gly Leu Leu Arg Arg
85 90 95
Ser Ala Ile Ala Ser Ser Pro Asp Arg Cys Val Thr Leu Glu Lys Ser
100 105 110
Thr Gln Thr Val Gln Gly Pro Asp Ser Ala Ala Cys Gly Leu Phe Cys
115 120 125
Cys Met Phe Leu His Ala Phe Val His Trp Pro Gln Ser Pro Met Asp
130 135 140
Arg Asn Pro Thr Met Asn Leu Leu Thr Gly Val Pro Asn Ser Met Leu
145 150 155 160
Gln Ser Pro Gln Val Glu Pro Thr Leu Arg Arg Asn Gln Glu Gln Leu
165 170 175
Tyr Ser Phe Leu Glu Arg His Ser Pro Tyr Phe Arg Arg His Ser Ala
180 185 190
Gln Ile Arg Arg Ala Thr Ser Phe Cys His Leu Gln Glu Met Gln Glu
195 200 205
Gly
<210> 75
<211> 199
<212> PRT
<213> Simian adenovirus 34
<400> 75
Met Ala Pro Arg Lys Lys Gln Gln Pro Pro Pro Gln Pro Tyr Met Leu
1 5 10 15
Leu Glu Glu Glu Glu Glu Asp Trp Asp Ser Gln Ala Glu Glu Val Ser
20 25 30
Asp Glu Glu Gln Glu Glu Met Met Glu Asp Trp Glu Glu Asp Ser Ser
35 40 45
Leu Asp Glu Glu Ala Ser Glu Ala Glu Glu Val Ala Asp Ala Thr Pro
50 55 60
Ser Pro Ser Val Ala Ala Pro Ser Pro Gly Pro Leu Lys Ser Ser Glu
65 70 75 80
Pro Ser Thr Ser Ala Ile Thr Ser Ala Pro Pro Ala Pro Ala Pro Pro
85 90 95
Ala Arg Arg Pro Asn Arg Arg Trp Asp Thr Thr Gly Thr Gly Val Gly
100 105 110
Lys Ser Lys Cys Pro Pro Pro Pro Pro Gln Gln Gln Gln Gln Gln Arg
115 120 125
Gln Gly Tyr Arg Ser Trp Arg Gly His Lys Asn Ala Ile Val Ala Cys
130 135 140
Leu Gln Asp Cys Gly Gly Asn Ile Ser Phe Ala Arg Arg Phe Leu Leu
145 150 155 160
Phe His His Gly Val Ala Phe Pro Arg Asn Val Leu His Tyr Tyr Arg
165 170 175
His Leu Tyr Ser Pro Tyr Cys Ser Gly Asp Pro Glu Ala Ala Ala Ala
180 185 190
Ala Thr Ala Ala Thr Thr Thr
195
<210> 76
<211> 227
<212> PRT
<213> Simian adenovirus 34
<400> 76
Met Ser Lys Glu Ile Pro Thr Pro Tyr Met Trp Ser Tyr Gln Pro Gln
1 5 10 15
Met Gly Leu Ala Ala Gly Ala Ala Gln Asp Tyr Ser Thr Arg Met Asn
20 25 30
Tyr Met Ser Ala Gly Pro His Met Ile Ser Gln Val Asn Gly Ile Arg
35 40 45
Ala Gln Arg Asn Gln Ile Leu Leu Glu Gln Ala Ala Ile Thr Ala Thr
50 55 60
Pro Arg His Asn Leu Asn Pro Arg Asn Trp Pro Ala Ala Leu Val Tyr
65 70 75 80
Gln Glu Thr Pro Ser Ala Thr Thr Val Leu Leu Pro Arg Asp Ala Gln
85 90 95
Ala Glu Val Gln Met Thr Asn Ser Gly Ala Gln Leu Ala Gly Gly Phe
100 105 110
Arg His Gly Ala Arg Pro Leu Arg Pro Gly Ile Arg His Leu Met Ile
115 120 125
Arg Gly Arg Gly Ile Gln Leu Asn Asp Glu Ser Val Ser Ser Ser Leu
130 135 140
Gly Leu Arg Pro Asp Gly Thr Phe Gln Leu Ala Gly Ser Gly Arg Ser
145 150 155 160
Ser Phe Thr Pro Arg Gln Ala Tyr Leu Thr Leu Gln Thr Ser Ser Ser
165 170 175
Glu Pro Arg Ser Gly Gly Ile Gly Thr Leu Gln Phe Val Glu Glu Phe
180 185 190
Val Pro Ser Val Tyr Phe Asn Pro Phe Ser Gly Pro Pro Gly Arg Tyr
195 200 205
Pro Asp Gln Phe Ile Pro Asn Phe Asp Ala Val Lys Asp Ser Ala Asp
210 215 220
Gly Tyr Asp
225
<210> 77
<211> 105
<212> PRT
<213> Simian adenovirus 34
<400> 77
Met Ser Gly Ala Glu Ala Glu Gln Leu Arg Leu Arg His Leu Glu His
1 5 10 15
Cys Arg Arg His Lys Cys Phe Ala Arg Gly Ser Gly Glu Phe Cys Tyr
20 25 30
Phe Gln Leu Pro Glu Glu His Thr Glu Gly Pro Ala His Gly Val Arg
35 40 45
Leu Thr Thr Gln Gly Glu Val Thr Cys Ser Leu Ile Arg Glu Phe Thr
50 55 60
Leu Arg Pro Leu Leu Val Glu Arg Glu Arg Gly Pro Cys Val Leu Thr
65 70 75 80
Ile Ala Cys Asn Cys Pro Asn Pro Gly Leu His Gln Asp Leu Cys Cys
85 90 95
His Leu Cys Ala Glu Phe Asn Lys Arg
100 105
<210> 78
<211> 191
<212> PRT
<213> Simian adenovirus 34
<400> 78
Val Pro Gln Ala Arg Arg Leu Leu Arg Thr His Leu Tyr Leu Leu Leu
1 5 10 15
Val Ala Gln Val Gln Gly Ser Pro Pro Lys Met Asn Arg Tyr Met Val
20 25 30
Leu Ser Ile Leu Gly Leu Leu Ala Leu Ala Ala Cys Ser Ala Ala Lys
35 40 45
Lys Glu Ile Thr Phe Glu Glu Pro Ala Cys Asn Val Thr Phe Lys Pro
50 55 60
Glu Gly Asp Gln Cys Thr Thr Leu Val Lys Cys Val Thr Asn His Glu
65 70 75 80
Arg Leu Arg Ile Asp Tyr Lys Asn Lys Thr Gly Arg Phe Ala Val Tyr
85 90 95
Ser Val Phe Thr Pro Gly Asp Pro Ser Asn Tyr Ser Val Thr Val Phe
100 105 110
Gln Gly Gly Gln Ser Lys Ile Phe Asn Tyr Thr Phe Pro Phe Tyr Glu
115 120 125
Leu Cys Asp Ala Val Met Tyr Met Ser Lys Gln Tyr Asn Leu Trp Pro
130 135 140
Pro Ser Pro Gln Ala Cys Val Glu Asn Thr Gly Ser Tyr Cys Cys Met
145 150 155 160
Ala Phe Ala Ile Thr Thr Leu Ala Leu Ile Cys Thr Val Leu Tyr Ile
165 170 175
Lys Phe Arg Gln Arg Arg Ile Phe Ile Asp Glu Lys Lys Met Pro
180 185 190
<210> 79
<211> 293
<212> PRT
<213> Simian adenovirus 34
<400> 79
Met Asn Ala Ile Thr Ser Leu Leu Ile Thr Thr Thr Leu Leu Ala Ile
1 5 10 15
Ala His Gly Leu Thr Arg Ile Glu Val Pro Val Gly Ser Asn Val Thr
20 25 30
Met Val Gly Pro Ala Gly Asn Ser Thr Leu Met Trp Glu Lys Phe Val
35 40 45
Arg Asn Gln Trp Val His Phe Cys Ser Asn Arg Ile Ser Ile Lys Pro
50 55 60
Arg Ala Ile Cys Asp Gly Gln Asn Leu Thr Leu Ile Asn Val Gln Met
65 70 75 80
Met Asp Ala Gly Tyr Tyr Tyr Gly Gln Arg Gly Glu Ile Ile Asn Tyr
85 90 95
Trp Arg Pro His Lys Asp Tyr Met Leu His Val Val Glu Ala Leu Pro
100 105 110
Thr Thr Thr Pro Thr Thr Thr Ser Pro Thr Thr Thr Thr Thr Thr Thr
115 120 125
Thr Thr Thr Ala Ala Arg His Thr Arg Lys Ser Thr Met Ile Ser Thr
130 135 140
Lys Pro Pro Arg Ala His Ser His Ala Gly Gly Pro Ile Gly Ala Thr
145 150 155 160
Ser Glu Thr Thr Glu Leu Cys Phe Cys Gln Cys Thr Asn Ala Ser Ala
165 170 175
His Glu Leu Phe Asp Leu Glu Asn Glu Asp Ala Gln Gln Ser Ser Ala
180 185 190
Cys Leu Thr Gln Glu Ala Val Glu Pro Val Ala Leu Lys Gln Ile Gly
195 200 205
Asp Ser Ile Ile Asp Ser Ser Ser Phe Ala Thr Pro Glu Tyr Pro Pro
210 215 220
Asp Ser Thr Phe His Ile Thr Gly Thr Lys Asp Pro Asn Leu Ser Phe
225 230 235 240
Tyr Leu Met Leu Leu Leu Cys Ile Ser Val Val Ser Ser Ala Leu Met
245 250 255
Leu Leu Gly Met Phe Cys Cys Leu Ile Cys Arg Arg Lys Arg Lys Ala
260 265 270
Arg Ser Gln Gly Gln Pro Leu Met Pro Phe Pro Tyr Pro Pro Asp Phe
275 280 285
Ala Asp Asn Lys Ile
290
<210> 80
<211> 90
<212> PRT
<213> Simian adenovirus 34
<400> 80
Met Pro Arg Ile Phe Leu Tyr Met Phe Leu Leu Pro Pro Phe Leu Gly
1 5 10 15
Cys Ser Thr Leu Ala Ala Val Ser His Leu Glu Val Asp Cys Leu Ser
20 25 30
Pro Phe Thr Val Tyr Leu Leu Tyr Gly Leu Val Thr Leu Thr Leu Ile
35 40 45
Cys Ser Leu Ile Thr Val Ile Ile Ala Phe Ile Gln Cys Ile Asp Tyr
50 55 60
Ile Cys Val Arg Leu Ala Tyr Phe Arg His His Pro Gln Tyr Arg Asp
65 70 75 80
Arg Asn Ile Ala Gln Leu Leu Arg Leu Leu
85 90
<210> 81
<211> 132
<212> PRT
<213> Simian adenovirus 34
<400> 81
Met His Lys Thr Val Ile Cys Leu Leu Ile Leu Cys Ile Leu Pro Thr
1 5 10 15
Leu Thr Ser Cys Gln Tyr Thr Thr Lys Ser Pro Arg Lys Arg His Ala
20 25 30
Ser Cys Arg Phe Thr Gln Leu Trp Asn Ile Pro Lys Cys Tyr Asn Glu
35 40 45
Lys Ser Glu Leu Ser Glu Ala Trp Leu Tyr Gly Val Ile Cys Val Leu
50 55 60
Val Phe Cys Ser Thr Val Phe Ala Leu Met Ile Tyr Pro Tyr Phe Asp
65 70 75 80
Leu Gly Trp Asn Ala Ile Asp Ala Met Asn Tyr Pro Thr Phe Pro Ala
85 90 95
Pro Glu Ile Ile Pro Leu Arg Gln Val Val Pro Val Val Val Asn Gln
100 105 110
Arg Pro Pro Ser Pro Thr Pro Thr Glu Ile Ser Tyr Phe Asn Leu Thr
115 120 125
Gly Gly Asp Asp
130
<210> 82
<211> 596
<212> PRT
<213> Simian adenovirus 34
<400> 82
Met Ser Asp Ser Cys Ser Cys Pro Ser Ala Pro Thr Ile Phe Met Leu
1 5 10 15
Leu Gln Met Lys Arg Thr Lys Thr Ser Asp Glu Ser Phe Asn Pro Val
20 25 30
Tyr Pro Tyr Asp Thr Glu Ser Gly Pro Pro Ser Val Pro Phe Leu Thr
35 40 45
Pro Pro Phe Val Ser Pro Asp Gly Phe Gln Glu Ser Pro Pro Gly Val
50 55 60
Leu Ser Leu Asn Leu Ala Glu Pro Leu Val Thr Ser His Gly Met Leu
65 70 75 80
Ala Leu Lys Met Gly Ser Gly Leu Ser Leu Asp Asp Ala Gly Asn Leu
85 90 95
Thr Ser Gln Asp Ile Thr Thr Ala Ser Pro Pro Leu Lys Lys Thr Lys
100 105 110
Thr Asn Leu Ser Leu Glu Thr Ser Ser Pro Leu Thr Val Ser Thr Ser
115 120 125
Gly Ala Leu Thr Val Ala Ala Ala Ala Pro Leu Ala Val Ala Gly Thr
130 135 140
Ser Leu Thr Met Gln Ser Glu Ala Pro Leu Thr Val Gln Asp Ala Lys
145 150 155 160
Leu Thr Leu Ala Thr Lys Gly Pro Leu Thr Val Ser Glu Gly Lys Leu
165 170 175
Ala Leu Gln Thr Ser Ala Pro Leu Thr Ala Ala Asp Ser Ser Thr Leu
180 185 190
Thr Val Ser Ala Thr Pro Pro Leu Ser Thr Ser Asn Gly Ser Leu Gly
195 200 205
Ile Asp Met Gln Ala Pro Ile Tyr Thr Thr Asn Gly Lys Leu Gly Leu
210 215 220
Asn Phe Gly Ala Pro Leu His Val Val Asp Ser Leu Asn Ala Leu Thr
225 230 235 240
Val Val Thr Gly Gln Gly Leu Thr Ile Asn Gly Thr Ala Leu Gln Thr
245 250 255
Arg Val Ser Gly Ala Leu Asn Tyr Asp Thr Ser Gly Asn Leu Glu Leu
260 265 270
Arg Ala Ala Gly Gly Met Arg Val Asp Ala Asn Gly Gln Leu Ile Leu
275 280 285
Asp Val Ala Tyr Pro Phe Asp Ala Gln Asn Asn Leu Ser Leu Arg Leu
290 295 300
Gly Gln Gly Pro Leu Phe Val Asn Ser Ala His Asn Leu Asp Val Asn
305 310 315 320
Tyr Asn Arg Gly Leu Tyr Leu Phe Thr Ser Gly Asn Thr Lys Lys Leu
325 330 335
Glu Val Asn Ile Lys Thr Ala Lys Gly Leu Ile Tyr Asp Asp Thr Ala
340 345 350
Ile Ala Ile Asn Ala Gly Asp Gly Leu Gln Phe Asp Ser Gly Ser Asp
355 360 365
Thr Asn Pro Leu Lys Thr Lys Leu Gly Leu Gly Leu Asp Tyr Asp Ser
370 375 380
Ser Arg Ala Ile Ile Ala Lys Leu Gly Thr Gly Leu Ser Phe Asp Asn
385 390 395 400
Thr Gly Ala Ile Thr Val Gly Asn Lys Asn Asp Asp Lys Leu Thr Leu
405 410 415
Trp Thr Thr Pro Asp Pro Ser Pro Asn Cys Arg Ile Tyr Ser Glu Lys
420 425 430
Asp Ala Lys Phe Thr Leu Val Leu Thr Lys Cys Gly Ser Gln Val Leu
435 440 445
Ala Ser Val Ser Val Leu Ser Val Lys Gly Ser Leu Ala Pro Ile Ser
450 455 460
Gly Thr Val Thr Ser Ala Gln Ile Val Leu Arg Phe Asp Glu Asn Gly
465 470 475 480
Val Leu Leu Ser Asn Ser Ser Leu Asp Pro Gln Tyr Trp Asn Tyr Arg
485 490 495
Lys Gly Asp Leu Thr Glu Gly Thr Ala Tyr Thr Asn Ala Val Gly Phe
500 505 510
Met Pro Asn Leu Thr Ala Tyr Pro Lys Thr Gln Ser Gln Thr Ala Lys
515 520 525
Ser Asn Ile Val Ser Gln Val Tyr Leu Asn Gly Asp Lys Ser Lys Pro
530 535 540
Met Thr Leu Thr Ile Thr Leu Asn Gly Thr Asn Glu Thr Gly Asp Ala
545 550 555 560
Thr Val Ser Thr Tyr Ser Met Ser Phe Ser Trp Asn Trp Asn Gly Ser
565 570 575
Asn Tyr Ile Asn Glu Thr Phe Gln Thr Asn Ser Phe Thr Phe Ser Tyr
580 585 590
Ile Ala Gln Glu
595
<210> 83
<211> 1530
<212> DNA
<213> Simian adenovirus 34
<220>
<221> CDS
<222> (10)..(1530)
<223> label=Elb\55K
<400> 83
gaaggatag atg gag cga aga gac cca ctt gag ttc ggg cta cgt cct gga 51
Met Glu Arg Arg Asp Pro Leu Glu Phe Gly Leu Arg Pro Gly
1 5 10
ttt tct ggc cat gca act gtg gag agc atg gat cag aca caa gaa cag 99
Phe Ser Gly His Ala Thr Val Glu Ser Met Asp Gln Thr Gln Glu Gln
15 20 25 30
gct gca act gtt gtc ttc cgt ccg ccc gtt gct gat tcc ggc gga gga 147
Ala Ala Thr Val Val Phe Arg Pro Pro Val Ala Asp Ser Gly Gly Gly
35 40 45
gca aca ggc cgg gtc aga gga ccg ggc ccg tcg gga tcc gga gga gag 195
Ala Thr Gly Arg Val Arg Gly Pro Gly Pro Ser Gly Ser Gly Gly Glu
50 55 60
ggc acc gag gcc ggg cga gag gag cgc gcc gaa cct ggg aac cgg gct 243
Gly Thr Glu Ala Gly Arg Glu Glu Arg Ala Glu Pro Gly Asn Arg Ala
65 70 75
gag cgg cca tcc aca tcg gga gtg aat gtc ggg cag gtg gtg gat ctt 291
Glu Arg Pro Ser Thr Ser Gly Val Asn Val Gly Gln Val Val Asp Leu
80 85 90
ttt cca gaa ctg cgg cgg att ttg act att agg gag gat ggg caa ttt 339
Phe Pro Glu Leu Arg Arg Ile Leu Thr Ile Arg Glu Asp Gly Gln Phe
95 100 105 110
gtt aag ggt ctt aag agg gag agg ggg gct tct gag cat aac gag gag 387
Val Lys Gly Leu Lys Arg Glu Arg Gly Ala Ser Glu His Asn Glu Glu
115 120 125
gcc agt aat tta gct ttt agc ttg atg acc aga cac cgt cca gag tgc 435
Ala Ser Asn Leu Ala Phe Ser Leu Met Thr Arg His Arg Pro Glu Cys
130 135 140
atc act ttt cag cag att aag gac aat tgt gcc aat gag ttg gat ctg 483
Ile Thr Phe Gln Gln Ile Lys Asp Asn Cys Ala Asn Glu Leu Asp Leu
145 150 155
ttg ggt cag aag tat agc ata gag cag ctg acc act tac tgg ctg cag 531
Leu Gly Gln Lys Tyr Ser Ile Glu Gln Leu Thr Thr Tyr Trp Leu Gln
160 165 170
ccg ggt gat gat ctg gag gaa gct att agg gtg tat gct aag gtg gcc 579
Pro Gly Asp Asp Leu Glu Glu Ala Ile Arg Val Tyr Ala Lys Val Ala
175 180 185 190
ctg cgg ccc gat tgc aag tac aag ctc aag ggg ctg gtg aat atc agg 627
Leu Arg Pro Asp Cys Lys Tyr Lys Leu Lys Gly Leu Val Asn Ile Arg
195 200 205
aat tgt tgc tac att tct ggc aac ggg gcg gag gtg gag ata gag acc 675
Asn Cys Cys Tyr Ile Ser Gly Asn Gly Ala Glu Val Glu Ile Glu Thr
210 215 220
gaa gac agg gtg gct ttc aga tgc agc atg atg aat atg tgg ccg ggg 723
Glu Asp Arg Val Ala Phe Arg Cys Ser Met Met Asn Met Trp Pro Gly
225 230 235
gtg ctg ggc atg gac ggg gtg gtg att atg aat gtg agg ttc acg ggg 771
Val Leu Gly Met Asp Gly Val Val Ile Met Asn Val Arg Phe Thr Gly
240 245 250
tcc aac ttt aac ggc acg gtg ttt ttg ggg aac acc aac ctg gtc ctg 819
Ser Asn Phe Asn Gly Thr Val Phe Leu Gly Asn Thr Asn Leu Val Leu
255 260 265 270
cac ggg gtg agc ttc tat ggg ttt aac aac acc tgt gtg gag gcc tgg 867
His Gly Val Ser Phe Tyr Gly Phe Asn Asn Thr Cys Val Glu Ala Trp
275 280 285
acc gat gtg aag gtc cgc ggt tgc gcc ttt tat gga tgt tgg aag gcc 915
Thr Asp Val Lys Val Arg Gly Cys Ala Phe Tyr Gly Cys Trp Lys Ala
290 295 300
ata gtg agc cgc cct aag agc agg agt tcc att aag aaa tgc ttg ttt 963
Ile Val Ser Arg Pro Lys Ser Arg Ser Ser Ile Lys Lys Cys Leu Phe
305 310 315
gag agg tgc acc ttg ggg atc ctg gcc gag ggc aac tgc agg gtg cgc 1011
Glu Arg Cys Thr Leu Gly Ile Leu Ala Glu Gly Asn Cys Arg Val Arg
320 325 330
cac aat gtg gcc tcc gag tgc ggt tgc ttc atg cta gtc aag agc gtg 1059
His Asn Val Ala Ser Glu Cys Gly Cys Phe Met Leu Val Lys Ser Val
335 340 345 350
gcg gta atc aag cat aat atg gtg tgc ggc aac agc gag gac aag gcc 1107
Ala Val Ile Lys His Asn Met Val Cys Gly Asn Ser Glu Asp Lys Ala
355 360 365
tca cag atg ctg acc tgc acg gat ggc aac tgc cac ttg ctg aag acc 1155
Ser Gln Met Leu Thr Cys Thr Asp Gly Asn Cys His Leu Leu Lys Thr
370 375 380
atc cat gta acc agc cac agc cgg aag gcc tgg ccc gtg ttc gag cac 1203
Ile His Val Thr Ser His Ser Arg Lys Ala Trp Pro Val Phe Glu His
385 390 395
aac ttg ctg acc cgc tgc tcc ttg cat ctg ggc aac agg cgg ggg gtg 1251
Asn Leu Leu Thr Arg Cys Ser Leu His Leu Gly Asn Arg Arg Gly Val
400 405 410
ttc ctg ccc tat caa tgc aac ttt agt cac acc aag atc ttg cta gag 1299
Phe Leu Pro Tyr Gln Cys Asn Phe Ser His Thr Lys Ile Leu Leu Glu
415 420 425 430
ccc gag agc atg tcc aag gtg aac ttg aac ggg gtg ttt gac atg acc 1347
Pro Glu Ser Met Ser Lys Val Asn Leu Asn Gly Val Phe Asp Met Thr
435 440 445
atg aag atc tgg aag gtg ctg agg tac gac gag acc agg tcc cgg tgc 1395
Met Lys Ile Trp Lys Val Leu Arg Tyr Asp Glu Thr Arg Ser Arg Cys
450 455 460
aga ccc tgc gag tgc ggg ggc aag cat atg agg aac cag ccc gtg atg 1443
Arg Pro Cys Glu Cys Gly Gly Lys His Met Arg Asn Gln Pro Val Met
465 470 475
ctg gat gtg acc gag gag ctg agg aca gac cac ttg gtt ctg gcc tgc 1491
Leu Asp Val Thr Glu Glu Leu Arg Thr Asp His Leu Val Leu Ala Cys
480 485 490
acc agg gcc gag ttt ggt tct agc gat gaa gac aca gat 1530
Thr Arg Ala Glu Phe Gly Ser Ser Asp Glu Asp Thr Asp
495 500 505
<210> 84
<211> 507
<212> PRT
<213> Simian adenovirus 34
<400> 84
Met Glu Arg Arg Asp Pro Leu Glu Phe Gly Leu Arg Pro Gly Phe Ser
1 5 10 15
Gly His Ala Thr Val Glu Ser Met Asp Gln Thr Gln Glu Gln Ala Ala
20 25 30
Thr Val Val Phe Arg Pro Pro Val Ala Asp Ser Gly Gly Gly Ala Thr
35 40 45
Gly Arg Val Arg Gly Pro Gly Pro Ser Gly Ser Gly Gly Glu Gly Thr
50 55 60
Glu Ala Gly Arg Glu Glu Arg Ala Glu Pro Gly Asn Arg Ala Glu Arg
65 70 75 80
Pro Ser Thr Ser Gly Val Asn Val Gly Gln Val Val Asp Leu Phe Pro
85 90 95
Glu Leu Arg Arg Ile Leu Thr Ile Arg Glu Asp Gly Gln Phe Val Lys
100 105 110
Gly Leu Lys Arg Glu Arg Gly Ala Ser Glu His Asn Glu Glu Ala Ser
115 120 125
Asn Leu Ala Phe Ser Leu Met Thr Arg His Arg Pro Glu Cys Ile Thr
130 135 140
Phe Gln Gln Ile Lys Asp Asn Cys Ala Asn Glu Leu Asp Leu Leu Gly
145 150 155 160
Gln Lys Tyr Ser Ile Glu Gln Leu Thr Thr Tyr Trp Leu Gln Pro Gly
165 170 175
Asp Asp Leu Glu Glu Ala Ile Arg Val Tyr Ala Lys Val Ala Leu Arg
180 185 190
Pro Asp Cys Lys Tyr Lys Leu Lys Gly Leu Val Asn Ile Arg Asn Cys
195 200 205
Cys Tyr Ile Ser Gly Asn Gly Ala Glu Val Glu Ile Glu Thr Glu Asp
210 215 220
Arg Val Ala Phe Arg Cys Ser Met Met Asn Met Trp Pro Gly Val Leu
225 230 235 240
Gly Met Asp Gly Val Val Ile Met Asn Val Arg Phe Thr Gly Ser Asn
245 250 255
Phe Asn Gly Thr Val Phe Leu Gly Asn Thr Asn Leu Val Leu His Gly
260 265 270
Val Ser Phe Tyr Gly Phe Asn Asn Thr Cys Val Glu Ala Trp Thr Asp
275 280 285
Val Lys Val Arg Gly Cys Ala Phe Tyr Gly Cys Trp Lys Ala Ile Val
290 295 300
Ser Arg Pro Lys Ser Arg Ser Ser Ile Lys Lys Cys Leu Phe Glu Arg
305 310 315 320
Cys Thr Leu Gly Ile Leu Ala Glu Gly Asn Cys Arg Val Arg His Asn
325 330 335
Val Ala Ser Glu Cys Gly Cys Phe Met Leu Val Lys Ser Val Ala Val
340 345 350
Ile Lys His Asn Met Val Cys Gly Asn Ser Glu Asp Lys Ala Ser Gln
355 360 365
Met Leu Thr Cys Thr Asp Gly Asn Cys His Leu Leu Lys Thr Ile His
370 375 380
Val Thr Ser His Ser Arg Lys Ala Trp Pro Val Phe Glu His Asn Leu
385 390 395 400
Leu Thr Arg Cys Ser Leu His Leu Gly Asn Arg Arg Gly Val Phe Leu
405 410 415
Pro Tyr Gln Cys Asn Phe Ser His Thr Lys Ile Leu Leu Glu Pro Glu
420 425 430
Ser Met Ser Lys Val Asn Leu Asn Gly Val Phe Asp Met Thr Met Lys
435 440 445
Ile Trp Lys Val Leu Arg Tyr Asp Glu Thr Arg Ser Arg Cys Arg Pro
450 455 460
Cys Glu Cys Gly Gly Lys His Met Arg Asn Gln Pro Val Met Leu Asp
465 470 475 480
Val Thr Glu Glu Leu Arg Thr Asp His Leu Val Leu Ala Cys Thr Arg
485 490 495
Ala Glu Phe Gly Ser Ser Asp Glu Asp Thr Asp
500 505
<210> 85
<211> 8220
<212> DNA
<213> Simian adenovirus 34
<220>
<221> CDS
<222> (10)..(2511)
<223> label=100K
<220>
<221> CDS
<222> (4182)..(4721)
<223> label=E3\CR1\alpha
<220>
<221> CDS
<222> (6303)..(7151)
<223> label=E3\CR1\gamma
<220>
<221> CDS
<222> (7832)..(8215)
<223> label=E3\14.7K
<400> 85
aaagagatc atg gag tct ctc atg cga gtc gag aag gag gag gac agc cta 51
Met Glu Ser Leu Met Arg Val Glu Lys Glu Glu Asp Ser Leu
1 5 10
acc gcc ccc tct gag ccc tcc acc acc gcc gcc acc acc gcc aat gcc 99
Thr Ala Pro Ser Glu Pro Ser Thr Thr Ala Ala Thr Thr Ala Asn Ala
15 20 25 30
gcc gcg gac gac gcg ccc acc gag acc acc gcc agt acc acc ctc ccc 147
Ala Ala Asp Asp Ala Pro Thr Glu Thr Thr Ala Ser Thr Thr Leu Pro
35 40 45
agc gac gca ccc ccg ctc gag aat gaa gtg ctg atc gag cag gac ccg 195
Ser Asp Ala Pro Pro Leu Glu Asn Glu Val Leu Ile Glu Gln Asp Pro
50 55 60
ggt ttt gtg agc gga gag gag gat gag gtg gat gag aag gag aag gag 243
Gly Phe Val Ser Gly Glu Glu Asp Glu Val Asp Glu Lys Glu Lys Glu
65 70 75
gag gtc gcc gcc tca gtg cca aaa gag gat aaa aag caa gac cag gac 291
Glu Val Ala Ala Ser Val Pro Lys Glu Asp Lys Lys Gln Asp Gln Asp
80 85 90
gac gca gat aag gat gag aca gca gtc ggg cgg ggg aac gga agc cat 339
Asp Ala Asp Lys Asp Glu Thr Ala Val Gly Arg Gly Asn Gly Ser His
95 100 105 110
gat gct gat gac ggc tac cta gac gtg gga gac gac gtg ctg ctt aag 387
Asp Ala Asp Asp Gly Tyr Leu Asp Val Gly Asp Asp Val Leu Leu Lys
115 120 125
cac ctg cac cgc cag tgc gtc atc gtc tgc gac gcg ctg cag gag cgc 435
His Leu His Arg Gln Cys Val Ile Val Cys Asp Ala Leu Gln Glu Arg
130 135 140
tgc gaa gtg ccc ctg gac gtg gcg gag gtc agc cgc gcc tac gag cgg 483
Cys Glu Val Pro Leu Asp Val Ala Glu Val Ser Arg Ala Tyr Glu Arg
145 150 155
cac ctc ttc gcg ccg cac gtg ccc ccc aag cgc cgg gag aac ggc acc 531
His Leu Phe Ala Pro His Val Pro Pro Lys Arg Arg Glu Asn Gly Thr
160 165 170
tgc gag ccc aac ccg cgt ctc aac ttc tac ccg gtc ttc gcg gta ccc 579
Cys Glu Pro Asn Pro Arg Leu Asn Phe Tyr Pro Val Phe Ala Val Pro
175 180 185 190
gag gtg ctg gcc acc tac cac atc ttc ttc caa aac tgc aag atc ccc 627
Glu Val Leu Ala Thr Tyr His Ile Phe Phe Gln Asn Cys Lys Ile Pro
195 200 205
ctc tcc tgc cgc gct aac cgc acc cgc gcc gac aaa acc ctg acc ctg 675
Leu Ser Cys Arg Ala Asn Arg Thr Arg Ala Asp Lys Thr Leu Thr Leu
210 215 220
cgg cag ggc gcc cac ata cct gat att gcc tct ctg gag gaa gtg ccc 723
Arg Gln Gly Ala His Ile Pro Asp Ile Ala Ser Leu Glu Glu Val Pro
225 230 235
aag atc ttc gag ggt ctc ggt cgc gac gag aaa cgg gcg gcg aac gct 771
Lys Ile Phe Glu Gly Leu Gly Arg Asp Glu Lys Arg Ala Ala Asn Ala
240 245 250
ctg cac gga gac agc gaa aac gag agt cac tcg ggg gtg ctg gtg gag 819
Leu His Gly Asp Ser Glu Asn Glu Ser His Ser Gly Val Leu Val Glu
255 260 265 270
ctc gag ggc gac aac gcg cgc ctg gcc gta ctc aag cgc agc ata gag 867
Leu Glu Gly Asp Asn Ala Arg Leu Ala Val Leu Lys Arg Ser Ile Glu
275 280 285
gtc acc cac ttt gcc tac ccg gcg ctc aac ctg ccc ccc aag gtc atg 915
Val Thr His Phe Ala Tyr Pro Ala Leu Asn Leu Pro Pro Lys Val Met
290 295 300
agt gtg gtc atg ggc gag ctc atc atg cgc cgc gcc cag ccc ctg gcc 963
Ser Val Val Met Gly Glu Leu Ile Met Arg Arg Ala Gln Pro Leu Ala
305 310 315
gcg gat gca aac ttg caa gag tcc tca gag gaa ggc ctg ccc gcg gtc 1011
Ala Asp Ala Asn Leu Gln Glu Ser Ser Glu Glu Gly Leu Pro Ala Val
320 325 330
agc gac gag cag ctg gcg cgc tgg ctg gag acc cgc gac ccc gcg cag 1059
Ser Asp Glu Gln Leu Ala Arg Trp Leu Glu Thr Arg Asp Pro Ala Gln
335 340 345 350
ctg gag gag cgg cgc aag ctc atg atg gcc gcg gtg ctg gtc acc gtg 1107
Leu Glu Glu Arg Arg Lys Leu Met Met Ala Ala Val Leu Val Thr Val
355 360 365
gag ctc gag tgt ctg cag cgc ttc ttc gcg gac ccc gag atg cag cgc 1155
Glu Leu Glu Cys Leu Gln Arg Phe Phe Ala Asp Pro Glu Met Gln Arg
370 375 380
aag ctc gag gag acc ctg cac tac acc ttc cgc cag ggc tac gtg cgc 1203
Lys Leu Glu Glu Thr Leu His Tyr Thr Phe Arg Gln Gly Tyr Val Arg
385 390 395
cag gcc tgc aag atc tcc aac gtg gag ctc tgc aac ctg gtc tcc tac 1251
Gln Ala Cys Lys Ile Ser Asn Val Glu Leu Cys Asn Leu Val Ser Tyr
400 405 410
ctg ggc atc ctg cac gag aac cgc ctc ggg cag aac gtc ctg cac tcc 1299
Leu Gly Ile Leu His Glu Asn Arg Leu Gly Gln Asn Val Leu His Ser
415 420 425 430
acc ctc aaa ggg gag gcg cgc cgc gac tac atc cgc gac tgc gcc tac 1347
Thr Leu Lys Gly Glu Ala Arg Arg Asp Tyr Ile Arg Asp Cys Ala Tyr
435 440 445
ctc ttc ctc tgc tac acc tgg cag acg gct atg ggg gtc tgg cag cag 1395
Leu Phe Leu Cys Tyr Thr Trp Gln Thr Ala Met Gly Val Trp Gln Gln
450 455 460
tgc ctg gag gag cgc aac ctc aag gag ctg gaa aag ctc ctc aag cgc 1443
Cys Leu Glu Glu Arg Asn Leu Lys Glu Leu Glu Lys Leu Leu Lys Arg
465 470 475
acc ctc agg gac ctc tgg acg ggc ttc aac gag cgc tcg gtg gcc gcc 1491
Thr Leu Arg Asp Leu Trp Thr Gly Phe Asn Glu Arg Ser Val Ala Ala
480 485 490
gcg ctg gcg gac atc atc ttc ccc gag cgc ttg ctc aag acc ctg cag 1539
Ala Leu Ala Asp Ile Ile Phe Pro Glu Arg Leu Leu Lys Thr Leu Gln
495 500 505 510
cag ggc ctg cca gac ttc acc agc cag agc atg ctg cag aac ttc agg 1587
Gln Gly Leu Pro Asp Phe Thr Ser Gln Ser Met Leu Gln Asn Phe Arg
515 520 525
act ttc atc ctt gag cgc tcg ggc atc ctg ccg gcc act tgc tgc gcg 1635
Thr Phe Ile Leu Glu Arg Ser Gly Ile Leu Pro Ala Thr Cys Cys Ala
530 535 540
ctg ccc agc gac ttc gtg ccc atc aag tac agg gag tgc ccg ccg ccg 1683
Leu Pro Ser Asp Phe Val Pro Ile Lys Tyr Arg Glu Cys Pro Pro Pro
545 550 555
ctc tgg ggc cac tgc tac ctc ttc cag ctg gcc aac tac ctc gcc tac 1731
Leu Trp Gly His Cys Tyr Leu Phe Gln Leu Ala Asn Tyr Leu Ala Tyr
560 565 570
cac tcg gac ctc atg gaa gac gtg agc ggc gag ggc ctg ctc gag tgc 1779
His Ser Asp Leu Met Glu Asp Val Ser Gly Glu Gly Leu Leu Glu Cys
575 580 585 590
cac tgc cgc tgc aac ctc tgc acg ccc cac cgc tct cta gtc tgc aac 1827
His Cys Arg Cys Asn Leu Cys Thr Pro His Arg Ser Leu Val Cys Asn
595 600 605
ccg cag ctg ctc agc gag agt cag att atc ggt acc ttc gag ctg cag 1875
Pro Gln Leu Leu Ser Glu Ser Gln Ile Ile Gly Thr Phe Glu Leu Gln
610 615 620
ggt ccc tcg cct gac gag aag tcc gcg gct ccg ggg ctg aaa ctc act 1923
Gly Pro Ser Pro Asp Glu Lys Ser Ala Ala Pro Gly Leu Lys Leu Thr
625 630 635
ccg ggg ctg tgg act tcc gcc tac cta cgc aaa ttt gta cct gag gac 1971
Pro Gly Leu Trp Thr Ser Ala Tyr Leu Arg Lys Phe Val Pro Glu Asp
640 645 650
tac cac gcc cac gag atc agg ttc tac gaa gac caa tcc cgc ccg ccc 2019
Tyr His Ala His Glu Ile Arg Phe Tyr Glu Asp Gln Ser Arg Pro Pro
655 660 665 670
aag gcg gag ctc acc gcc tgc gtc atc acc cag ggg cac atc ctg ggc 2067
Lys Ala Glu Leu Thr Ala Cys Val Ile Thr Gln Gly His Ile Leu Gly
675 680 685
caa ttg caa gcc atc aac aaa gcc cgc cga gag ttc ttg ctg aaa aag 2115
Gln Leu Gln Ala Ile Asn Lys Ala Arg Arg Glu Phe Leu Leu Lys Lys
690 695 700
ggt cgg ggg gtg tac ctg gac ccc cag tcc ggc gag gag cta aac ccg 2163
Gly Arg Gly Val Tyr Leu Asp Pro Gln Ser Gly Glu Glu Leu Asn Pro
705 710 715
cta ccc ccg ccg ccg ccc cag cag cgg gac ctt gct tcc cag gat ggc 2211
Leu Pro Pro Pro Pro Pro Gln Gln Arg Asp Leu Ala Ser Gln Asp Gly
720 725 730
acc cag aaa gaa gca gca gcc gcc gcc gca gcc ata cat gct tct gga 2259
Thr Gln Lys Glu Ala Ala Ala Ala Ala Ala Ala Ile His Ala Ser Gly
735 740 745 750
gga aga gga gga gga ctg gga cag tca ggc aga gga ggt ttc gga cga 2307
Gly Arg Gly Gly Gly Leu Gly Gln Ser Gly Arg Gly Gly Phe Gly Arg
755 760 765
gga gca gga gga gat gat gga aga ctg gga gga gga cag cag cct aga 2355
Gly Ala Gly Gly Asp Asp Gly Arg Leu Gly Gly Gly Gln Gln Pro Arg
770 775 780
cga gga agc ttc aga ggc cga aga ggt ggc aga cgc aac acc atc acc 2403
Arg Gly Ser Phe Arg Gly Arg Arg Gly Gly Arg Arg Asn Thr Ile Thr
785 790 795
ctc ggt cgc agc ccc ctc gcc ggg gcc cct gaa atc ctc cga acc cag 2451
Leu Gly Arg Ser Pro Leu Ala Gly Ala Pro Glu Ile Leu Arg Thr Gln
800 805 810
cac cag cgc tat aac ctc cgc tcc tcc ggc gcc ggc gcc acc cgc ccg 2499
His Gln Arg Tyr Asn Leu Arg Ser Ser Gly Ala Gly Ala Thr Arg Pro
815 820 825 830
cag acc caa ccg tagatgggac accacaggaa ccggggtcgg taagtccaag 2551
Gln Thr Gln Pro
tgcccgccgc cgccaccgca gcagcagcag cagcagcgcc agggctaccg ctcgtggcgc 2611
gggcacaaga acgccatagt cgcctgcttg caagactgcg ggggcaacat ctctttcgcc 2671
cgccgcttcc tgctattcca ccacggggtc gcctttcccc gcaatgtcct gcattactac 2731
cgtcatctct acagccccta ctgcagcggc gacccagagg cggcagcggc agccacagcg 2791
gcgaccacca cctaggaaga tatcctccgc gggcaagaca gcggcagcag cggccaggag 2851
acccgcggca gcagcggcgg gagcggtggg cgcactgcgc ctctcgccca acgaacccct 2911
ctcgacccgg gagctcagac acaggatctt ccccactttg tatgccatct tccaacagag 2971
cagaggccag gagcaggagc tgaaaataaa aaacagatct ctgcgctccc tcacccgcag 3031
ctgtctgtat cacaaaagcg aagatcagct tcggcgcacg ctggaggacg cggaggcact 3091
cttcagcaaa tactgcgcgc tcactcttaa agactagctc cgcgcccttc tcgaatttag 3151
gcgggagaaa actacgtcat cgccggccgc cgcccagccc gcccagccga gatgagcaaa 3211
gagattccca cgccatacat gtggagctac cagccgcaga tgggactcgc ggcgggagcg 3271
gcccaggact actccacccg catgaactac atgagcgcgg gaccccacat gatctcacag 3331
gtcaacggga tccgcgccca gcgaaaccaa atactgctgg aacaggcggc catcaccgcc 3391
acgccccgcc ataatctcaa cccccgaaat tggcccgccg ccctcgtgta ccaggaaacc 3451
ccctccgcca ccaccgtact acttccgcgt gacgcccagg ccgaagtcca gatgactaac 3511
tcaggggcgc agctcgcggg cggctttcgt cacggggcgc ggccgctccg accaggtata 3571
agacacctga tgatcagagg ccgaggtatc cagctcaacg acgagtcggt gagctcttcg 3631
ctcggtctcc gtccggacgg aactttccag ctcgccggat ccggccgctc ttcgttcacg 3691
ccccgccagg cgtacctgac tctgcagacc tcgtcctcgg agccccgctc cggaggcatc 3751
ggaaccctcc agttcgtgga ggagttcgtg ccctcggtct acttcaaccc cttctcggga 3811
cctcccggac gctaccccga ccagttcatt ccgaactttg acgcggtgaa ggactcggcg 3871
gacggctacg actgaatgtc aggtgccgag gcagagcagc ttcgcctgag acacctcgag 3931
cactgccgcc gccacaagtg cttcgcccgc ggttccggtg agttctgcta ctttcagcta 3991
cccgaggagc ataccgaggg gccggcgcac ggcgtccgcc tgaccaccca gggcgaggtt 4051
acctgttccc tcatccggga gttcaccctc cgtcccctgc tagtggagcg ggagcggggt 4111
ccctgtgtcc taactatcgc ctgcaactgc cctaaccctg gattacatca agatctttgc 4171
tgtcatctct gtg ctg agt tta ata aac gct gag atc aga atc tac tgg 4220
Val Leu Ser Leu Ile Asn Ala Glu Ile Arg Ile Tyr Trp
835 840 845
ggc tcc tgt cgc cat cct gtg aac gcc acc gtc ttc acc cac ccc gac 4268
Gly Ser Cys Arg His Pro Val Asn Ala Thr Val Phe Thr His Pro Asp
850 855 860
cag gcc cag gcg aac ctc acc tgc ggt ctg cat cgg agg gcc aag aag 4316
Gln Ala Gln Ala Asn Leu Thr Cys Gly Leu His Arg Arg Ala Lys Lys
865 870 875
tac ctc acc tgg tac ttc aac ggc acc ccc ttt gtg gtt tac aac agc 4364
Tyr Leu Thr Trp Tyr Phe Asn Gly Thr Pro Phe Val Val Tyr Asn Ser
880 885 890 895
ttc gac ggg gac gga gtc tcc ctg aaa gac cag ctc tcc ggt ctc agc 4412
Phe Asp Gly Asp Gly Val Ser Leu Lys Asp Gln Leu Ser Gly Leu Ser
900 905 910
tac tcc atc cac aag aac acc acc ctc caa ctc ttc cct ccc tac ctg 4460
Tyr Ser Ile His Lys Asn Thr Thr Leu Gln Leu Phe Pro Pro Tyr Leu
915 920 925
ccg gga acc tac gag tgc gtc acc ggc cgc tgc acc cac ctc acc cgc 4508
Pro Gly Thr Tyr Glu Cys Val Thr Gly Arg Cys Thr His Leu Thr Arg
930 935 940
ctg atc gta aac cag agc ttt ccg gga aca gat aac tcc ctc ttc ccc 4556
Leu Ile Val Asn Gln Ser Phe Pro Gly Thr Asp Asn Ser Leu Phe Pro
945 950 955
aga aca gga ggt gag ctc agg aaa ctc ccc ggg gac cag ggc gga gac 4604
Arg Thr Gly Gly Glu Leu Arg Lys Leu Pro Gly Asp Gln Gly Gly Asp
960 965 970 975
gta cct tcg acc ctt gtg ggg tta gga ttt ttt att acc ggg ttg ctg 4652
Val Pro Ser Thr Leu Val Gly Leu Gly Phe Phe Ile Thr Gly Leu Leu
980 985 990
gct ctt tta atc aaa gct tcc ttg aga ttt gtt ctt tcc ttc tac gtg 4700
Ala Leu Leu Ile Lys Ala Ser Leu Arg Phe Val Leu Ser Phe Tyr Val
995 1000 1005
tat gaa cac ctc agc ctc caa taactctacc ctttcttcgg aatcaggtga 4751
Tyr Glu His Leu Ser Leu Gln
1010
cttctctgaa atcgggcttg gtgtgctgct tactctgttg atttttttcc ttatcatact 4811
cagccttctg tgcctcaggc tcgccgcctg ctgcgcacac atctatatct actgctggtt 4871
gctcaagtgc aggggtcgcc acccaagatg aacaggtaca tggtcctatc gatcctaggc 4931
ctgctggccc tggcggcctg cagcgccgcc aaaaaagaga ttacctttga ggagcccgct 4991
tgcaatgtaa ctttcaagcc cgagggtgac caatgcacca ccctcgtcaa atgcgttacc 5051
aatcatgaga ggctgcgcat cgactacaaa aacaaaactg gccggtttgc ggtctatagt 5111
gtgtttacgc ccggagaccc ctctaactac tctgtcaccg tcttccaggg cggacagtct 5171
aagatattca attacacttt ccctttttat gagttgtgcg atgcggtcat gtacatgtca 5231
aaacagtaca acctgtggcc tccctctccc caggcgtgtg tggaaaatac tgggtcttac 5291
tgctgtatgg ctttcgcaat cactacgctc gctctaatct gcacggtgct atatataaaa 5351
ttcaggcaga ggcgaatctt tatcgatgaa aagaaaatgc cttgatcgct aacaccggct 5411
ttctatctgc agaatgaatg caatcacctc cctactaatc accaccaccc tccttgcgat 5471
tgcccatggg ttgacacgaa tcgaagtgcc agtggggtcc aatgtcacca tggtgggccc 5531
cgccggcaat tccaccctca tgtgggaaaa atttgtccgc aatcaatggg ttcatttctg 5591
ctctaaccga atcagtatca agcccagagc catctgcgat gggcaaaatc taactctgat 5651
caatgtgcaa atgatggatg ctgggtacta ttacgggcag cggggagaaa tcattaatta 5711
ctggcgaccc cacaaggact acatgctgca tgtagtcgag gcacttccca ctaccacccc 5771
cactaccacc tctcccacca ccaccactac tactactacc actaccgctg cccgtcatac 5831
ccgcaaaagc accatgatta gcacaaagcc ccctcgtgct cactcccacg ccggcgggcc 5891
catcggtgcg acctcagaaa ccaccgagct ttgcttctgc caatgcacta acgccagcgc 5951
tcatgaactg ttcgacctgg agaatgagga tgcccagcag agctccgctt gcctgaccca 6011
ggaggctgtg gagcccgttg ccctgaagca gatcggtgat tcaataattg actcttcttc 6071
ttttgccact cccgaatacc ctcccgattc tactttccac atcacgggta ccaaagaccc 6131
taacctctct ttctacctga tgctgctgct ctgtatctct gtggtctctt ccgcgctgat 6191
gttactgggg atgttctgct gcctgatctg ccgcagaaag agaaaagctc gctctcaggg 6251
ccaaccactg atgcccttcc cctacccccc ggattttgca gataacaaga t atg agc 6308
Met Ser
1015
tcg ctg ctg aca cta acc gct tta cta gcc tgc gct cta acc ctt 6353
Ser Leu Leu Thr Leu Thr Ala Leu Leu Ala Cys Ala Leu Thr Leu
1020 1025 1030
gtc gct tgc gac tcg aga ttc cac aat gtc aca gct gtg gca gga 6398
Val Ala Cys Asp Ser Arg Phe His Asn Val Thr Ala Val Ala Gly
1035 1040 1045
gaa aat gtt act ttc aac tcc acg gcc gat acc cag tgg tcg tgg 6443
Glu Asn Val Thr Phe Asn Ser Thr Ala Asp Thr Gln Trp Ser Trp
1050 1055 1060
agt ggc tca ggt agc tac tta act atc tgc aat agc tcc act tcc 6488
Ser Gly Ser Gly Ser Tyr Leu Thr Ile Cys Asn Ser Ser Thr Ser
1065 1070 1075
ccc agc ata tcc cca acc aag tac caa tgc aat gcc agc ctg ttc 6533
Pro Ser Ile Ser Pro Thr Lys Tyr Gln Cys Asn Ala Ser Leu Phe
1080 1085 1090
acc ctc atc aac gct tcc acc ctg gac aat gga ctc tat gta ggc 6578
Thr Leu Ile Asn Ala Ser Thr Leu Asp Asn Gly Leu Tyr Val Gly
1095 1100 1105
tat gta ccc ttt ggt ggg caa gga aag acc cac gct tac aac ctg 6623
Tyr Val Pro Phe Gly Gly Gln Gly Lys Thr His Ala Tyr Asn Leu
1110 1115 1120
gaa gtt cgc cag ccc aga acc act acc caa gct tct ccc acc acc 6668
Glu Val Arg Gln Pro Arg Thr Thr Thr Gln Ala Ser Pro Thr Thr
1125 1130 1135
acc acc acc acc acc atc acc agc agc agc agc agc agc agc cac 6713
Thr Thr Thr Thr Thr Ile Thr Ser Ser Ser Ser Ser Ser Ser His
1140 1145 1150
agc agc agc agc aga tta ttg act ttg gtt ttg gcc agc tca tct 6758
Ser Ser Ser Ser Arg Leu Leu Thr Leu Val Leu Ala Ser Ser Ser
1155 1160 1165
gcc gct acc cag gcc atc tac agc tct gtg ccc gaa acc act cag 6803
Ala Ala Thr Gln Ala Ile Tyr Ser Ser Val Pro Glu Thr Thr Gln
1170 1175 1180
atc tac cgc cca gaa acg acc acc gcc acc acc cta cac acc tcc 6848
Ile Tyr Arg Pro Glu Thr Thr Thr Ala Thr Thr Leu His Thr Ser
1185 1190 1195
agc gat cag atg ccg acc aac atc acc ccc ttg gct ctt caa atg 6893
Ser Asp Gln Met Pro Thr Asn Ile Thr Pro Leu Ala Leu Gln Met
1200 1205 1210
gga ctt aca agc ccc act cca aaa cca gtg gat gcg gcc gag gtc 6938
Gly Leu Thr Ser Pro Thr Pro Lys Pro Val Asp Ala Ala Glu Val
1215 1220 1225
tcc gcc ctc gtc aat gac tgg gcg ggg ctg gga atg tgg tgg ttc 6983
Ser Ala Leu Val Asn Asp Trp Ala Gly Leu Gly Met Trp Trp Phe
1230 1235 1240
gcc ata ggc atg atg gcg ctc tgc ctg ctt ctg ctc tgg ctc atc 7028
Ala Ile Gly Met Met Ala Leu Cys Leu Leu Leu Leu Trp Leu Ile
1245 1250 1255
tgc tgc ctc cac cgc agg cga gcc aga ccc ccc atc tat aga ccc 7073
Cys Cys Leu His Arg Arg Arg Ala Arg Pro Pro Ile Tyr Arg Pro
1260 1265 1270
atc att gtc ctg aac ccc gat aat gat ggg atc cat aga ttg gat 7118
Ile Ile Val Leu Asn Pro Asp Asn Asp Gly Ile His Arg Leu Asp
1275 1280 1285
ggc ctg aaa aac cta ctt ttt tct ttt aca gta tgataaattg 7161
Gly Leu Lys Asn Leu Leu Phe Ser Phe Thr Val
1290 1295
agacatgcct cgcattttct tgtacatgtt ccttctccca ccttttctgg ggtgttctac 7221
gctggccgct gtgtctcacc tggaggtaga ctgcctctca cccttcactg tctacctgct 7281
ttacggattg gtcaccctca ctctcatctg cagcctaatc acagtaatca tcgccttcat 7341
ccagtgcatt gattacatct gtgtgcgcct cgcatacttc agacaccacc cgcagtaccg 7401
agacaggaac attgcccaac ttctaagact gctctaatca tgcataagac tgtgatctgc 7461
cttctgatcc tctgcatcct gcccaccctc acctcctgcc agtacaccac aaaatctccg 7521
cgcaaaagac atgcctcctg ccgcttcacc caactgtgga atatacccaa atgctacaac 7581
gaaaagagcg agctctccga agcttggctg tatggggtca tctgtgtctt agttttctgc 7641
agcactgtct ttgccctcat gatctacccc tactttgatt tgggatggaa cgcgatcgat 7701
gccatgaatt accccacctt tcccgcaccc gagataattc cactgcgaca agttgtaccc 7761
gttgtcgtta atcaacgccc cccatcccct acgcccactg aaatcagcta ctttaaccta 7821
acaggcggag atg act gac gcc cta gat cta gaa atg gac ggc atc agt 7870
Met Thr Asp Ala Leu Asp Leu Glu Met Asp Gly Ile Ser
1300 1305 1310
acc gag cag cgt ctc cta gag agg cgc agg cag gcg gct gag caa 7915
Thr Glu Gln Arg Leu Leu Glu Arg Arg Arg Gln Ala Ala Glu Gln
1315 1320 1325
gag cgc ctc aat cag gag ctc cga gat ctc gtt aac ctg cac cag 7960
Glu Arg Leu Asn Gln Glu Leu Arg Asp Leu Val Asn Leu His Gln
1330 1335 1340
tgc aaa aga ggc atc ttt tgt ctg gta aag cag gcc aaa gtc acc 8005
Cys Lys Arg Gly Ile Phe Cys Leu Val Lys Gln Ala Lys Val Thr
1345 1350 1355
tac gag aag acc ggc aac agc cac cgc ctc agt tac aaa ttg ccc 8050
Tyr Glu Lys Thr Gly Asn Ser His Arg Leu Ser Tyr Lys Leu Pro
1360 1365 1370
acc cag cgc cag aag ctg gtg ctc atg gtg ggt gag aat ccc atc 8095
Thr Gln Arg Gln Lys Leu Val Leu Met Val Gly Glu Asn Pro Ile
1375 1380 1385
acc gtc acc cag cac tcg gta gag acc gag ggg tgt ctg cac tcc 8140
Thr Val Thr Gln His Ser Val Glu Thr Glu Gly Cys Leu His Ser
1390 1395 1400
ccc tgt cgg ggt cca gaa gac ctc tgc acc ctg gta aag acc ctg 8185
Pro Cys Arg Gly Pro Glu Asp Leu Cys Thr Leu Val Lys Thr Leu
1405 1410 1415
tgc ggt ctc aga gat tta gtc ccc ttt aac taatc 8220
Cys Gly Leu Arg Asp Leu Val Pro Phe Asn
1420 1425
<210> 86
<211> 834
<212> PRT
<213> Simian adenovirus 34
<400> 86
Met Glu Ser Leu Met Arg Val Glu Lys Glu Glu Asp Ser Leu Thr Ala
1 5 10 15
Pro Ser Glu Pro Ser Thr Thr Ala Ala Thr Thr Ala Asn Ala Ala Ala
20 25 30
Asp Asp Ala Pro Thr Glu Thr Thr Ala Ser Thr Thr Leu Pro Ser Asp
35 40 45
Ala Pro Pro Leu Glu Asn Glu Val Leu Ile Glu Gln Asp Pro Gly Phe
50 55 60
Val Ser Gly Glu Glu Asp Glu Val Asp Glu Lys Glu Lys Glu Glu Val
65 70 75 80
Ala Ala Ser Val Pro Lys Glu Asp Lys Lys Gln Asp Gln Asp Asp Ala
85 90 95
Asp Lys Asp Glu Thr Ala Val Gly Arg Gly Asn Gly Ser His Asp Ala
100 105 110
Asp Asp Gly Tyr Leu Asp Val Gly Asp Asp Val Leu Leu Lys His Leu
115 120 125
His Arg Gln Cys Val Ile Val Cys Asp Ala Leu Gln Glu Arg Cys Glu
130 135 140
Val Pro Leu Asp Val Ala Glu Val Ser Arg Ala Tyr Glu Arg His Leu
145 150 155 160
Phe Ala Pro His Val Pro Pro Lys Arg Arg Glu Asn Gly Thr Cys Glu
165 170 175
Pro Asn Pro Arg Leu Asn Phe Tyr Pro Val Phe Ala Val Pro Glu Val
180 185 190
Leu Ala Thr Tyr His Ile Phe Phe Gln Asn Cys Lys Ile Pro Leu Ser
195 200 205
Cys Arg Ala Asn Arg Thr Arg Ala Asp Lys Thr Leu Thr Leu Arg Gln
210 215 220
Gly Ala His Ile Pro Asp Ile Ala Ser Leu Glu Glu Val Pro Lys Ile
225 230 235 240
Phe Glu Gly Leu Gly Arg Asp Glu Lys Arg Ala Ala Asn Ala Leu His
245 250 255
Gly Asp Ser Glu Asn Glu Ser His Ser Gly Val Leu Val Glu Leu Glu
260 265 270
Gly Asp Asn Ala Arg Leu Ala Val Leu Lys Arg Ser Ile Glu Val Thr
275 280 285
His Phe Ala Tyr Pro Ala Leu Asn Leu Pro Pro Lys Val Met Ser Val
290 295 300
Val Met Gly Glu Leu Ile Met Arg Arg Ala Gln Pro Leu Ala Ala Asp
305 310 315 320
Ala Asn Leu Gln Glu Ser Ser Glu Glu Gly Leu Pro Ala Val Ser Asp
325 330 335
Glu Gln Leu Ala Arg Trp Leu Glu Thr Arg Asp Pro Ala Gln Leu Glu
340 345 350
Glu Arg Arg Lys Leu Met Met Ala Ala Val Leu Val Thr Val Glu Leu
355 360 365
Glu Cys Leu Gln Arg Phe Phe Ala Asp Pro Glu Met Gln Arg Lys Leu
370 375 380
Glu Glu Thr Leu His Tyr Thr Phe Arg Gln Gly Tyr Val Arg Gln Ala
385 390 395 400
Cys Lys Ile Ser Asn Val Glu Leu Cys Asn Leu Val Ser Tyr Leu Gly
405 410 415
Ile Leu His Glu Asn Arg Leu Gly Gln Asn Val Leu His Ser Thr Leu
420 425 430
Lys Gly Glu Ala Arg Arg Asp Tyr Ile Arg Asp Cys Ala Tyr Leu Phe
435 440 445
Leu Cys Tyr Thr Trp Gln Thr Ala Met Gly Val Trp Gln Gln Cys Leu
450 455 460
Glu Glu Arg Asn Leu Lys Glu Leu Glu Lys Leu Leu Lys Arg Thr Leu
465 470 475 480
Arg Asp Leu Trp Thr Gly Phe Asn Glu Arg Ser Val Ala Ala Ala Leu
485 490 495
Ala Asp Ile Ile Phe Pro Glu Arg Leu Leu Lys Thr Leu Gln Gln Gly
500 505 510
Leu Pro Asp Phe Thr Ser Gln Ser Met Leu Gln Asn Phe Arg Thr Phe
515 520 525
Ile Leu Glu Arg Ser Gly Ile Leu Pro Ala Thr Cys Cys Ala Leu Pro
530 535 540
Ser Asp Phe Val Pro Ile Lys Tyr Arg Glu Cys Pro Pro Pro Leu Trp
545 550 555 560
Gly His Cys Tyr Leu Phe Gln Leu Ala Asn Tyr Leu Ala Tyr His Ser
565 570 575
Asp Leu Met Glu Asp Val Ser Gly Glu Gly Leu Leu Glu Cys His Cys
580 585 590
Arg Cys Asn Leu Cys Thr Pro His Arg Ser Leu Val Cys Asn Pro Gln
595 600 605
Leu Leu Ser Glu Ser Gln Ile Ile Gly Thr Phe Glu Leu Gln Gly Pro
610 615 620
Ser Pro Asp Glu Lys Ser Ala Ala Pro Gly Leu Lys Leu Thr Pro Gly
625 630 635 640
Leu Trp Thr Ser Ala Tyr Leu Arg Lys Phe Val Pro Glu Asp Tyr His
645 650 655
Ala His Glu Ile Arg Phe Tyr Glu Asp Gln Ser Arg Pro Pro Lys Ala
660 665 670
Glu Leu Thr Ala Cys Val Ile Thr Gln Gly His Ile Leu Gly Gln Leu
675 680 685
Gln Ala Ile Asn Lys Ala Arg Arg Glu Phe Leu Leu Lys Lys Gly Arg
690 695 700
Gly Val Tyr Leu Asp Pro Gln Ser Gly Glu Glu Leu Asn Pro Leu Pro
705 710 715 720
Pro Pro Pro Pro Gln Gln Arg Asp Leu Ala Ser Gln Asp Gly Thr Gln
725 730 735
Lys Glu Ala Ala Ala Ala Ala Ala Ala Ile His Ala Ser Gly Gly Arg
740 745 750
Gly Gly Gly Leu Gly Gln Ser Gly Arg Gly Gly Phe Gly Arg Gly Ala
755 760 765
Gly Gly Asp Asp Gly Arg Leu Gly Gly Gly Gln Gln Pro Arg Arg Gly
770 775 780
Ser Phe Arg Gly Arg Arg Gly Gly Arg Arg Asn Thr Ile Thr Leu Gly
785 790 795 800
Arg Ser Pro Leu Ala Gly Ala Pro Glu Ile Leu Arg Thr Gln His Gln
805 810 815
Arg Tyr Asn Leu Arg Ser Ser Gly Ala Gly Ala Thr Arg Pro Gln Thr
820 825 830
Gln Pro
<210> 87
<211> 180
<212> PRT
<213> Simian adenovirus 34
<400> 87
Val Leu Ser Leu Ile Asn Ala Glu Ile Arg Ile Tyr Trp Gly Ser Cys
1 5 10 15
Arg His Pro Val Asn Ala Thr Val Phe Thr His Pro Asp Gln Ala Gln
20 25 30
Ala Asn Leu Thr Cys Gly Leu His Arg Arg Ala Lys Lys Tyr Leu Thr
35 40 45
Trp Tyr Phe Asn Gly Thr Pro Phe Val Val Tyr Asn Ser Phe Asp Gly
50 55 60
Asp Gly Val Ser Leu Lys Asp Gln Leu Ser Gly Leu Ser Tyr Ser Ile
65 70 75 80
His Lys Asn Thr Thr Leu Gln Leu Phe Pro Pro Tyr Leu Pro Gly Thr
85 90 95
Tyr Glu Cys Val Thr Gly Arg Cys Thr His Leu Thr Arg Leu Ile Val
100 105 110
Asn Gln Ser Phe Pro Gly Thr Asp Asn Ser Leu Phe Pro Arg Thr Gly
115 120 125
Gly Glu Leu Arg Lys Leu Pro Gly Asp Gln Gly Gly Asp Val Pro Ser
130 135 140
Thr Leu Val Gly Leu Gly Phe Phe Ile Thr Gly Leu Leu Ala Leu Leu
145 150 155 160
Ile Lys Ala Ser Leu Arg Phe Val Leu Ser Phe Tyr Val Tyr Glu His
165 170 175
Leu Ser Leu Gln
180
<210> 88
<211> 283
<212> PRT
<213> Simian adenovirus 34
<400> 88
Met Ser Ser Leu Leu Thr Leu Thr Ala Leu Leu Ala Cys Ala Leu Thr
1 5 10 15
Leu Val Ala Cys Asp Ser Arg Phe His Asn Val Thr Ala Val Ala Gly
20 25 30
Glu Asn Val Thr Phe Asn Ser Thr Ala Asp Thr Gln Trp Ser Trp Ser
35 40 45
Gly Ser Gly Ser Tyr Leu Thr Ile Cys Asn Ser Ser Thr Ser Pro Ser
50 55 60
Ile Ser Pro Thr Lys Tyr Gln Cys Asn Ala Ser Leu Phe Thr Leu Ile
65 70 75 80
Asn Ala Ser Thr Leu Asp Asn Gly Leu Tyr Val Gly Tyr Val Pro Phe
85 90 95
Gly Gly Gln Gly Lys Thr His Ala Tyr Asn Leu Glu Val Arg Gln Pro
100 105 110
Arg Thr Thr Thr Gln Ala Ser Pro Thr Thr Thr Thr Thr Thr Thr Ile
115 120 125
Thr Ser Ser Ser Ser Ser Ser Ser His Ser Ser Ser Ser Arg Leu Leu
130 135 140
Thr Leu Val Leu Ala Ser Ser Ser Ala Ala Thr Gln Ala Ile Tyr Ser
145 150 155 160
Ser Val Pro Glu Thr Thr Gln Ile Tyr Arg Pro Glu Thr Thr Thr Ala
165 170 175
Thr Thr Leu His Thr Ser Ser Asp Gln Met Pro Thr Asn Ile Thr Pro
180 185 190
Leu Ala Leu Gln Met Gly Leu Thr Ser Pro Thr Pro Lys Pro Val Asp
195 200 205
Ala Ala Glu Val Ser Ala Leu Val Asn Asp Trp Ala Gly Leu Gly Met
210 215 220
Trp Trp Phe Ala Ile Gly Met Met Ala Leu Cys Leu Leu Leu Leu Trp
225 230 235 240
Leu Ile Cys Cys Leu His Arg Arg Arg Ala Arg Pro Pro Ile Tyr Arg
245 250 255
Pro Ile Ile Val Leu Asn Pro Asp Asn Asp Gly Ile His Arg Leu Asp
260 265 270
Gly Leu Lys Asn Leu Leu Phe Ser Phe Thr Val
275 280
<210> 89
<211> 128
<212> PRT
<213> Simian adenovirus 34
<400> 89
Met Thr Asp Ala Leu Asp Leu Glu Met Asp Gly Ile Ser Thr Glu Gln
1 5 10 15
Arg Leu Leu Glu Arg Arg Arg Gln Ala Ala Glu Gln Glu Arg Leu Asn
20 25 30
Gln Glu Leu Arg Asp Leu Val Asn Leu His Gln Cys Lys Arg Gly Ile
35 40 45
Phe Cys Leu Val Lys Gln Ala Lys Val Thr Tyr Glu Lys Thr Gly Asn
50 55 60
Ser His Arg Leu Ser Tyr Lys Leu Pro Thr Gln Arg Gln Lys Leu Val
65 70 75 80
Leu Met Val Gly Glu Asn Pro Ile Thr Val Thr Gln His Ser Val Glu
85 90 95
Thr Glu Gly Cys Leu His Ser Pro Cys Arg Gly Pro Glu Asp Leu Cys
100 105 110
Thr Leu Val Lys Thr Leu Cys Gly Leu Arg Asp Leu Val Pro Phe Asn
115 120 125
<210> 90
<211> 960
<212> DNA
<213> Simian adenovirus 34
<220>
<221> CDS
<222> (9)..(549)
<223> label=Ela
<220>
<221> CDS
<222> (662)..(960)
<223> label=Ela
<400> 90
gggaaaaa atg aga cat ttc acc tac gat ggc ggt gtg ctc acc ggc cag 50
Met Arg His Phe Thr Tyr Asp Gly Gly Val Leu Thr Gly Gln
1 5 10
ctg gct gct gag gtc ctg gac acc ctg atc gag gag gta ttg gcc gat 98
Leu Ala Ala Glu Val Leu Asp Thr Leu Ile Glu Glu Val Leu Ala Asp
15 20 25 30
aat tat cct ccc tcg act cct ttt gag cca cct aca ctt cac gaa ctc 146
Asn Tyr Pro Pro Ser Thr Pro Phe Glu Pro Pro Thr Leu His Glu Leu
35 40 45
tac gat ctg gat gtg gtg ggg ccc agc gat ccg aac gag cag gcg gtt 194
Tyr Asp Leu Asp Val Val Gly Pro Ser Asp Pro Asn Glu Gln Ala Val
50 55 60
tcc agt ttt ttt cca gag tcc atg ttg ttg gcc agc cag gag ggg gtc 242
Ser Ser Phe Phe Pro Glu Ser Met Leu Leu Ala Ser Gln Glu Gly Val
65 70 75
gaa ctt gag acc cct cct ccg atc gtg gat tcc ccc gat ccg ccg cag 290
Glu Leu Glu Thr Pro Pro Pro Ile Val Asp Ser Pro Asp Pro Pro Gln
80 85 90
ctg act agg cag ccc gag cgc tgt gcg gga cct gag act atg ccc cag 338
Leu Thr Arg Gln Pro Glu Arg Cys Ala Gly Pro Glu Thr Met Pro Gln
95 100 105 110
ctg cta cct gag gtg atc gat ctc acc tgt aat gag tct ggt ttt cca 386
Leu Leu Pro Glu Val Ile Asp Leu Thr Cys Asn Glu Ser Gly Phe Pro
115 120 125
ccc agc gag gat gag gac gaa gag ggt gag cag ttt gtg tta gat tct 434
Pro Ser Glu Asp Glu Asp Glu Glu Gly Glu Gln Phe Val Leu Asp Ser
130 135 140
gtg gaa caa ccc ggg cga gga tgc agg tct tgt caa tat cac cgg aaa 482
Val Glu Gln Pro Gly Arg Gly Cys Arg Ser Cys Gln Tyr His Arg Lys
145 150 155
aac aca gga gac tcc cag att atg tgt tct ctg tgt tat atg aag atg 530
Asn Thr Gly Asp Ser Gln Ile Met Cys Ser Leu Cys Tyr Met Lys Met
160 165 170
acc tgt atg ttt att tac a gtaagtttat catcggtggg caggtgggct 579
Thr Cys Met Phe Ile Tyr
175 180
atagtgtggg tggtggtctt tgggggtttt ttaatatatg tcaggggtta tgctgaagac 639
ttttttattg tgatttttaa ag gt cca gtg tct gag ccc gag caa gaa cct 690
Ser Pro Val Ser Glu Pro Glu Gln Glu Pro
185 190
gaa ccg gag cct gag cct tct cgc ccc agg aga aag cct gtg atc tta 738
Glu Pro Glu Pro Glu Pro Ser Arg Pro Arg Arg Lys Pro Val Ile Leu
195 200 205
act aga ccc agc gca ccg gta gcg aga ggc ctc agc agc gcg gag acc 786
Thr Arg Pro Ser Ala Pro Val Ala Arg Gly Leu Ser Ser Ala Glu Thr
210 215 220
acc gac tcc ggt gct tcc tca tca ccc ccg gag att cac ccc ctg gtg 834
Thr Asp Ser Gly Ala Ser Ser Ser Pro Pro Glu Ile His Pro Leu Val
225 230 235
ccc ctg tgt ccc gtt aag ccc gtt gcc gtg aga gtc agt ggg cgg cgg 882
Pro Leu Cys Pro Val Lys Pro Val Ala Val Arg Val Ser Gly Arg Arg
240 245 250
tct gct gtg gag tgc att gag gac ttg ctt ttt gat tca cag gaa cct 930
Ser Ala Val Glu Cys Ile Glu Asp Leu Leu Phe Asp Ser Gln Glu Pro
255 260 265 270
ttg gac ttg agc ttg aaa cgc ccc agg cat 960
Leu Asp Leu Ser Leu Lys Arg Pro Arg His
275 280
<210> 91
<211> 280
<212> PRT
<213> Simian adenovirus 34
<400> 91
Met Arg His Phe Thr Tyr Asp Gly Gly Val Leu Thr Gly Gln Leu Ala
1 5 10 15
Ala Glu Val Leu Asp Thr Leu Ile Glu Glu Val Leu Ala Asp Asn Tyr
20 25 30
Pro Pro Ser Thr Pro Phe Glu Pro Pro Thr Leu His Glu Leu Tyr Asp
35 40 45
Leu Asp Val Val Gly Pro Ser Asp Pro Asn Glu Gln Ala Val Ser Ser
50 55 60
Phe Phe Pro Glu Ser Met Leu Leu Ala Ser Gln Glu Gly Val Glu Leu
65 70 75 80
Glu Thr Pro Pro Pro Ile Val Asp Ser Pro Asp Pro Pro Gln Leu Thr
85 90 95
Arg Gln Pro Glu Arg Cys Ala Gly Pro Glu Thr Met Pro Gln Leu Leu
100 105 110
Pro Glu Val Ile Asp Leu Thr Cys Asn Glu Ser Gly Phe Pro Pro Ser
115 120 125
Glu Asp Glu Asp Glu Glu Gly Glu Gln Phe Val Leu Asp Ser Val Glu
130 135 140
Gln Pro Gly Arg Gly Cys Arg Ser Cys Gln Tyr His Arg Lys Asn Thr
145 150 155 160
Gly Asp Ser Gln Ile Met Cys Ser Leu Cys Tyr Met Lys Met Thr Cys
165 170 175
Met Phe Ile Tyr Ser Pro Val Ser Glu Pro Glu Gln Glu Pro Glu Pro
180 185 190
Glu Pro Glu Pro Ser Arg Pro Arg Arg Lys Pro Val Ile Leu Thr Arg
195 200 205
Pro Ser Ala Pro Val Ala Arg Gly Leu Ser Ser Ala Glu Thr Thr Asp
210 215 220
Ser Gly Ala Ser Ser Ser Pro Pro Glu Ile His Pro Leu Val Pro Leu
225 230 235 240
Cys Pro Val Lys Pro Val Ala Val Arg Val Ser Gly Arg Arg Ser Ala
245 250 255
Val Glu Cys Ile Glu Asp Leu Leu Phe Asp Ser Gln Glu Pro Leu Asp
260 265 270
Leu Ser Leu Lys Arg Pro Arg His
275 280
<210> 92
<211> 930
<212> DNA
<213> Simian adenovirus 34
<220>
<221> CDS
<222> (7)..(336)
<223> label=33K
<220>
<221> CDS
<222> (590)..(925)
<223> label=33K
<400> 92
cccagg atg gca ccc aga aag aag cag cag ccg ccg ccg cag cca tac 48
Met Ala Pro Arg Lys Lys Gln Gln Pro Pro Pro Gln Pro Tyr
1 5 10
atg ctt ctg gag gaa gag gag gag gac tgg gac agt cag gca gag gag 96
Met Leu Leu Glu Glu Glu Glu Glu Asp Trp Asp Ser Gln Ala Glu Glu
15 20 25 30
gtt tcg gac gag gag cag gag gag atg atg gaa gac tgg gag gag gac 144
Val Ser Asp Glu Glu Gln Glu Glu Met Met Glu Asp Trp Glu Glu Asp
35 40 45
agc agc cta gac gag gaa gct tca gag gcc gaa gag gtg gca gac gca 192
Ser Ser Leu Asp Glu Glu Ala Ser Glu Ala Glu Glu Val Ala Asp Ala
50 55 60
aca cca tca ccc tcg gtc gca gcc ccc tcg ccg ggg ccc ctg aaa tcc 240
Thr Pro Ser Pro Ser Val Ala Ala Pro Ser Pro Gly Pro Leu Lys Ser
65 70 75
tcc gaa ccc agc acc agc gct ata acc tcc gct cct ccg gcg ccg gcg 288
Ser Glu Pro Ser Thr Ser Ala Ile Thr Ser Ala Pro Pro Ala Pro Ala
80 85 90
cca ccc gcc cgc aga ccc aac cgt aga tgg gac acc aca gga acc ggg 336
Pro Pro Ala Arg Arg Pro Asn Arg Arg Trp Asp Thr Thr Gly Thr Gly
95 100 105 110
gtcggtaagt ccaagtgccc gccgccgcca ccgcagcagc agcagcagca gcgccagggc 396
taccgctcgt ggcgcgggca caagaacgcc atagtcgcct gcttgcaaga ctgcgggggc 456
aacatctctt tcgcccgccg cttcctgcta ttccaccacg gggtcgcctt tccccgcaat 516
gtcctgcatt actaccgtca tctctacagc ccctactgca gcggcgaccc agaggcggca 576
gcggcagcca cag cgg cga cca cca cct agg aag ata tcc tcc gcg ggc 625
Arg Arg Pro Pro Pro Arg Lys Ile Ser Ser Ala Gly
115 120
aag aca gcg gca gca gcg gcc agg aga ccc gcg gca gca gcg gcg gga 673
Lys Thr Ala Ala Ala Ala Ala Arg Arg Pro Ala Ala Ala Ala Ala Gly
125 130 135
gcg gtg ggc gca ctg cgc ctc tcg ccc aac gaa ccc ctc tcg acc cgg 721
Ala Val Gly Ala Leu Arg Leu Ser Pro Asn Glu Pro Leu Ser Thr Arg
140 145 150
gag ctc aga cac agg atc ttc ccc act ttg tat gcc atc ttc caa cag 769
Glu Leu Arg His Arg Ile Phe Pro Thr Leu Tyr Ala Ile Phe Gln Gln
155 160 165 170
agc aga ggc cag gag cag gag ctg aaa ata aaa aac aga tct ctg cgc 817
Ser Arg Gly Gln Glu Gln Glu Leu Lys Ile Lys Asn Arg Ser Leu Arg
175 180 185
tcc ctc acc cgc agc tgt ctg tat cac aaa agc gaa gat cag ctt cgg 865
Ser Leu Thr Arg Ser Cys Leu Tyr His Lys Ser Glu Asp Gln Leu Arg
190 195 200
cgc acg ctg gag gac gcg gag gca ctc ttc agc aaa tac tgc gcg ctc 913
Arg Thr Leu Glu Asp Ala Glu Ala Leu Phe Ser Lys Tyr Cys Ala Leu
205 210 215
act ctt aaa gac tagct 930
Thr Leu Lys Asp
220
<210> 93
<211> 222
<212> PRT
<213> Simian adenovirus 34
<400> 93
Met Ala Pro Arg Lys Lys Gln Gln Pro Pro Pro Gln Pro Tyr Met Leu
1 5 10 15
Leu Glu Glu Glu Glu Glu Asp Trp Asp Ser Gln Ala Glu Glu Val Ser
20 25 30
Asp Glu Glu Gln Glu Glu Met Met Glu Asp Trp Glu Glu Asp Ser Ser
35 40 45
Leu Asp Glu Glu Ala Ser Glu Ala Glu Glu Val Ala Asp Ala Thr Pro
50 55 60
Ser Pro Ser Val Ala Ala Pro Ser Pro Gly Pro Leu Lys Ser Ser Glu
65 70 75 80
Pro Ser Thr Ser Ala Ile Thr Ser Ala Pro Pro Ala Pro Ala Pro Pro
85 90 95
Ala Arg Arg Pro Asn Arg Arg Trp Asp Thr Thr Gly Thr Gly Arg Arg
100 105 110
Pro Pro Pro Arg Lys Ile Ser Ser Ala Gly Lys Thr Ala Ala Ala Ala
115 120 125
Ala Arg Arg Pro Ala Ala Ala Ala Ala Gly Ala Val Gly Ala Leu Arg
130 135 140
Leu Ser Pro Asn Glu Pro Leu Ser Thr Arg Glu Leu Arg His Arg Ile
145 150 155 160
Phe Pro Thr Leu Tyr Ala Ile Phe Gln Gln Ser Arg Gly Gln Glu Gln
165 170 175
Glu Leu Lys Ile Lys Asn Arg Ser Leu Arg Ser Leu Thr Arg Ser Cys
180 185 190
Leu Tyr His Lys Ser Glu Asp Gln Leu Arg Arg Thr Leu Glu Asp Ala
195 200 205
Glu Ala Leu Phe Ser Lys Tyr Cys Ala Leu Thr Leu Lys Asp
210 215 220
<210> 94
<211> 70
<212> DNA
<213> Artificial Sequence
<220>
<223> oligomer P6 Top
<400> 94
aattgtttaa actacgtaat taggccggcc gcgcacgcgt gtcattaatt aagctagata 60
tcgtttaaac 70
<210> 95
<211> 68
<212> DNA
<213> Artificial Sequence
<220>
<223> oligomer P6 Bot
<400> 95
gtttaaacga tatctagctt aattaatgac acgcgtgcgc ggccggccta attacgtagt 60
ttaaacat 68
<210> 96
<211> 38
<212> DNA
<213> Artificial Sequence
<220>
<223> oligomer 951 Top
<400> 96
cgcgcatatg gatcgatcgc tagcgatcga tcgaattc 38
<210> 97
<211> 38
<212> DNA
<213> Artificial Sequence
<220>
<223> oligomer 951 bot
<400> 97
cgcggaattc gatcgatcgc tagcgatcga tccatatg 38
<210> 98
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> oligomer SOE 1
<400> 98
catcatcaat aatatacctt attttgg 27
<210> 99
<211> 19
<212> DNA
<213> Artificial Sequence
<220>
<223> oligomer SOE 2
<400> 99
aacggagact ttgacccgg 19
<210> 100
<211> 42
<212> DNA
<213> Artificial Sequence
<220>
<223> oligomer SOE 3
<400> 100
ccgggtcaaa gtctccgttt aactataacg gtcctaaggt ag 42
<210> 101
<211> 31
<212> DNA
<213> Artificial Sequence
<220>
<223> oligomer SOE 4
<400> 101
gatccatatg tgccatttca ttacctcttt c 31
<210> 102
<211> 318
<212> DNA
<213> Simian adenovirus 40 antisense
<400> 102
ccgggtcaaa gtctccgttt aactataacg gtcctaaggt agcgaaagct cagatctccc 60
gatcccctat ggtgcactct cagtacaatc tgctctgatg ccgcatagtt aagccagtat 120
ctgctccctg cttgtgtgtt ggaggtcgct gagtagtgcg cgagcaaaat ttaagctaca 180
acaaggcaag gcttgaccga caattgcatg aagaatctgc ttagggttag gcgttttgcg 240
ctgcttcgcg atgtacgggc cagatataca tctatgtcgg gtgcggagaa agaggtaatg 300
aaatggcaca tatggatc 318
<210> 103
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> primer pBRfwd
<400> 103
cacctgacgt ctaagaaacc 20
<210> 104
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> primer pBRrev
<400> 104
tgagcgagga agcggaag 18
<210> 105
<211> 660
<212> DNA
<213> Unknown
<220>
<223> plasmid sequence
<400> 105
gatatcattt ccccgaaaag tgccacctga cgtaactata acggtcctaa ggtagcgaaa 60
gctcagatct cccgatcccc tatggtgcac tctcagtaca atctgctctg atgccgcata 120
gttaagccag tatctgctcc ctgcttgtgt gttggaggtc gctgagtagt gcgcgagcaa 180
aatttaagct acaacaaggc aaggcttgac cgacaattgc atgaagaatc tgcttagggt 240
taggcgtttt gcgctgcttc gcgatgtacg ggccagatat acgcggtacg aaaccgctga 300
tcagcctcga ctgtgccttc tagttgccag ccatctgttg tttgcccctc ccccgtgcct 360
tccttgaccc tggaaggtgc cactcccact gtcctttcct aataaaatga ggaaattgca 420
tcgcattgtc tgagtaggtg tcattctatt ctggggggtg gggtggggca ggacagcaag 480
ggggaggatt gggaagacaa tagcaggcat gctggggatg cggtgggctc tatggcttct 540
gaggcggaaa gaaccagcag atctgcagat ctgaattcat ctatgtcggg tgcggagaaa 600
gaggtaatga aatggcatta tgggtattat gggtctgcat taatgaatcg gccagatatc 660
Claims (21)
- (a) SAdV-40의 헥손 단백질, SEQ ID NO: 11의 아미노산 1 내지 960; SAdV-31의 헥손 단백질, SEQ ID NO: 42의 아미노산 1 내지 954; SAdV-34의 헥손 단백질, SEQ ID NO: 73의 아미노산 1 내지 958;
(b) SAdV-40의 펜톤 단백질, SEQ ID NO: 6의 아미노산 1 내지 593; SAdV-31의 펜톤 단백질, SEQ ID NO: 37의 아미노산 1 내지 589; SAdV-34의 펜톤 단백질, SEQ ID NO: 68의 아미노산 1 내지 617; 및
(c) SAdV-40의 섬유 단백질, SEQ ID NO: 20의 아미노산 1 내지 543, SAdV-31의 섬유 단백질, SEQ ID NO: 51의 아미노산 1 내지 596; SAdV-34의 섬유 단백질, SEQ ID NO: 82의 아미노산 1 내지 596;
로 구성되는 군으로부터 선택되는 캡시드 단백질을 포함하는 캡시드를 가지며,
상기 캡시드는 숙주 세포에서 그것의 전사, 번역 및/또는 발현을 지시하는 발현 조절 서열에 작동가능하게 연결된 유전자를 전달하는 이종성 분자를 단백질막으로 싸는 아데노바이러스. - 제 1 항에 있어서, 복제 및 단백질 막화에 필요한 5' 및 3' 아데노바이러스 시스-구성요소를 추가로 포함하는 것을 특징으로 하는 아데노바이러스.
- 제 1 항에 있어서, 상기 아데노바이러스는 E1 유전자의 모두 또는 일부를 결핍하는 것을 특징으로 하는 아데노바이러스.
- 제 3 항에 있어서, 상기 아데노바이러스는 복제-결함인 것을 특징으로 하는 아데노바이러스.
- 제 5 항에 있어서, 상기 바이러스는 하이브리드 캡시드인 것을 특징으로 하는 아데노바이러스.
- 제 5 항에 있어서, 상기 벡터는 SAdV-40, SAdV-31, 및 SAdV-34로부터 선택되는 하나 이상의 캡시드 단백질을 포함하는 것을 특징으로 하는 아데노바이러스.
- SAdV 헥손 단백질의 단편은 길이에 있어서 약 50개의 아미노산의 N-말단 또는 C-말단 절단을 가지는 SEQ ID NO: 11, 42 또는 73의 SAdV 헥손 단백질 또는
SEQ ID NO: 11, 42 또는 73의 아미노산 잔기 125 내지 443;
SEQ ID NO: 11, 42 또는 73의 아미노산 잔기 138 내지 441;
SEQ ID NO: 11, 42 또는 73의 아미노산 잔기 138 내지 163;
SEQ ID NO: 11, 42 또는 73의 아미노산 잔기 170 내지 176; 및
SEQ ID NO: 11, 42 또는 73의 아미노산 잔기 404 내지 430으로 구성되는 군으로부터 선택되는 유인원 아데노바이러스 헥손 단백질의 단편 및 SAdV에 이종성인 핵산 서열을 함유하는 헥손을 포함하는 캡시드를 가지는 재조합 아데노바이러스. - 제 7 항에 있어서, 캡시드는 SAdV-40, SAdV-31 또는 SAdV-34 섬유 단백질을 추가로 포함하는 것을 특징으로 하는 재조합 아데노바이러스.
- 제 7 항에 있어서, 캡시드는 추가로 SAdV-40, SAdV-31 또는 SAdV-34 펜톤 단백질을 포함하는 것을 특징으로 하는 재조합 아데노바이러스.
- 제 7 항에 있어서, 상기 아데노바이러스는 복제 및 단백질 막화에 필요한 5' 및 3' 아데노바이러스 시스-구성요소를 포함하는 슈도타입화된 아데노바이러스이고, 상기 시스-구성요소는 아데노바이러스 5' 역위 말단 반복 및 아데노바이러스 3' 역위 말단 반복을 포함하는 것을 특징으로 하는 재조합 아데노바이러스.
- 제 7 항에 있어서, 아데노바이러스는 숙주 세포에서 생성물의 발현을 지시하는 서열에 작동가능하게 연결된 생성물을 암호화하는 핵산 서열을 포함하는 것을 특징으로 하는 재조합 아데노바이러스.
- 제 7 항에 있어서, 재조합 아데노바이러스는 하나 이상의 아데노바이러스 유전자를 포함하는 것을 특징으로 하는 재조합 아데노바이러스.
- 제 7 항에 있어서, 재조합 아데노바이러스는 복제-결함인 것을 특징으로 하는 재조합 아데노바이러스.
- 제 13 항에 있어서, 재조합 아데노바이러스는 아데노바이러스 E1에서 결실된 것을 특징으로 하는 재조합 아데노바이러스.
- 약학적으로 허용가능한 담체 중에 제 1 항 내지 제 14 항 중 어느 한 항의 바이러스를 포함하는 조성물.
- 제 1 항 내지 제 14 항 중 어느 한 항에 따르는 바이러스를 피험자에게 전달하는 단계를 포함하는 아데노바이러스 수용체를 가지는 세포를 표적화하는 방법.
- 유인원 아데노바이러스 40 핵산 SEQ ID NO: 1의 1 내지 37718 및 그것의 보체;
유인원 아데노바이러스 31 핵산 SEQ ID NO: 32의 1 내지 37828 및 그것의 보체; 및
유인원 아데노바이러스 34 핵산 SEQ ID NO: 63의 1 내지 37799 및 그것의 보체
로 구성되는 군으로부터 선택되는 분리된 유인원 아데노바이러스 아데노바이러스 핵산. - (a) 5' 역위 말단 반복 (ITR) 서열;
(b) 아데노바이러스 E1a 영역;
(c) 아데노바이러스 E1b 영역, 또는 작은 T, 거대한 T, 및 IX 영역에 대한 오픈리딩프레임으로 구성되는 군 중에서 선택되는 그것의 단편;
(d) pTP, 폴리머라아제, 및 IVa 영역에 대한 오픈리딩프레임을 포함하는 E2b 영역;
(e) L1 영역, 또는 52/55 kD 단백질, 및 IIIa 단백질에 대한 오픈리딩프레임으로 구성되는 군 중에서 선택되는 그것의 단편;
(f) L2 영역, 또는 펜톤, VII, VI, 및 pX 단백질에 대한 오픈리딩프레임으로 구성되는 군으로부터 선택되는 그것의 단편;
(g) L3 영역, 또는 VI, 헥손, 및 엔도프로테아제 단백질에 대한 오픈리딩프레임으로 구성되는 군으로부터 선택되는 그것의 단편;
(h) DNA-결합 단백질(DBP)에 대한 오픈리딩프레임을 포함하는 E2a 단백질;
(i) L4 영역, 또는 100 kD 단백질, 33 kD 상동체, 22kD 상동체 및 VIII에 대한 오픈리딩프레임으로 구성되는 군으로부터 선택되는 그것의 단편;
(j) E3 영역, 또는 12.5K 단백질, CR1-알파, gp19K; CR1-베타; CR1-감마; RID-알파; RID-베타; 및 14.7 K에 대한 오픈리딩프레임으로 구성되는 군으로부터 선택되는 그것의 단편;
(k) L5 영역, 또는 섬유 단백질에 대한 오픈리딩프레임으로부터 선택되는 그것의 단편;
(l) E4 영역, 또는 E4 ORF6/7, E4 ORF6, E4 ORF4, E4 ORF3, E4 ORF2, 및 E4 ORF1에 대한 오픈리딩프레임으로 구성되는 군으로부터 선택되는 그것의 단편; 및
(m) 유인원 아데노바이러스 40, SEQ ID NO:1; SAdV-31, SEQ ID NO: 32; SAdV-34, SEQ ID NO: 63의 3' ITR
로 구성되는 하나 이상의 군으로부터 선택되는 유인원 아데노바이러스 핵산 서열을 포함하는 벡터. - 제 18 항에 따르는 핵산 서열에 의해 암호화되는 유인원 아데노바이러스 단백질.
- SEQ ID NO: 29, 60 및 91의 아미노산 서열로부터 선택되는 E1a;
SEQ ID NO: 22, 53 및 64의 아미노산 서열로부터 선택되는 E1b, 작은 T/19K;
SEQ ID NO: 2, 33 및 84의 아미노산 서열로부터 선택되는 E1b, 거대 T/55K;
SEQ ID NO: 3, 34 및 65의 아미노산 서열로부터 선택되는 IX;
SEQ ID NO: 4, 35 및 66의 아미노산 서열로부터 선택되는 52/55D;
SEQ ID NO: 5, 36 및 67의 아미노산 서열로부터 선택되는 IIIa;
SEQ ID NO: 6, 37 및 68의 아미노산 서열로부터 선택되는 펜톤;
SEQ ID NO: 7, 38 및 69의 아미노산 서열로부터 선택되는 VII;
SEQ ID NO: 8, 39 및 70의 아미노산 서열로부터 선택되는 V;
SEQ ID NO: 9, 40 및 71의 아미노산 서열로부터 선택되는 pX;
SEQ ID NO: 10, 41 및 72의 아미노산 서열로부터 선택되는 VI;
SEQ ID NO: 11, 42 및 73의 아미노산 서열로부터 선택되는 헥손;
SEQ ID NO: 12, 43 및 74의 아미노산 서열로부터 선택되는 엔도프로테아제;
SEQ ID NO: 13, 44 및 86의 아미노산 서열로부터 선택되는 100 kD;
SEQ ID NO: 31, 62 및 93의 아미노산 서열로부터 선택되는 33 kD;
SEQ ID NO: 24, 55 및 75의 아미노산 서열로부터 선택되는 22 kD;
SEQ ID NO: 14, 45 및 76의 아미노산 서열로부터 선택되는 VIII;
SEQ ID NO: 15, 46 및 77의 아미노산 서열로부터 선택되는 12.5K;
SEQ ID NO: 25, 56 및 87의 아미노산 서열로부터 선택되는 CR1-알파;
SEQ ID NO: 16, 47 및 78의 아미노산 서열로부터 선택되는 gp19K;
SEQ ID NO: 17, 48 및 79의 아미노산 서열로부터 선택되는 CR1-베타;
SEQ ID NO: 26, 57 및 88의 아미노산 서열로부터 선택되는 CR1-감마;
SEQ ID NO: 18, 49 및 80의 아미노산 서열로부터 선택되는 RID-알파;
SEQ ID NO: 19, 50 및 81의 아미노산 서열로부터 선택되는 RID-베타;
SEQ ID NO: 27, 58 및 89의 아미노산 서열로부터 선택되는 14.7K; 및
SEQ LD NO: 20, 51 및 82의 아미노산 서열로부터 선택되는 섬유소
로 구성되는 군으로부터 선택되는 하나 이상의 유인원 아데노바이러스 단백질을 포함하는 조성물. - 제 20 항에 따르는 조성물을 피험자에 전달하는 단계를 포함하며, 상기 조성물은 헥손, 펜톤 및 섬유소로부터 선택되는 하나 이상의 유인원 아데노바이러스 SAdV-40, -31, 및 -34 단백질인 아데노바이러스 수용체를 가지는 세포를 표적화하는 방법.
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| Application Number | Priority Date | Filing Date | Title |
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| US449607P | 2007-11-28 | 2007-11-28 | |
| US446507P | 2007-11-28 | 2007-11-28 | |
| US456807P | 2007-11-28 | 2007-11-28 | |
| US61/004,568 | 2007-11-28 | ||
| US61/004,496 | 2007-11-28 | ||
| US61/004,465 | 2007-11-28 |
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| Publication Number | Publication Date |
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| KR20100105630A true KR20100105630A (ko) | 2010-09-29 |
| KR101614369B1 KR101614369B1 (ko) | 2016-04-21 |
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| US (1) | US8231880B2 (ko) |
| EP (2) | EP2220217A2 (ko) |
| JP (2) | JP5758124B2 (ko) |
| KR (1) | KR101614369B1 (ko) |
| CN (1) | CN102131920B (ko) |
| AU (1) | AU2008350937B2 (ko) |
| BR (1) | BRPI0819774A2 (ko) |
| CA (1) | CA2707029A1 (ko) |
| MX (1) | MX2010005860A (ko) |
| WO (1) | WO2009105084A2 (ko) |
| ZA (1) | ZA201003895B (ko) |
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| KR20180011265A (ko) * | 2015-06-12 | 2018-01-31 | 글락소스미스클라인 바이오로지칼즈 에스.에이. | 아데노바이러스 폴리뉴클레오티드 및 폴리펩티드 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20180011265A (ko) * | 2015-06-12 | 2018-01-31 | 글락소스미스클라인 바이오로지칼즈 에스.에이. | 아데노바이러스 폴리뉴클레오티드 및 폴리펩티드 |
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| Publication number | Publication date |
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| JP2011504751A (ja) | 2011-02-17 |
| JP5758124B2 (ja) | 2015-08-05 |
| WO2009105084A2 (en) | 2009-08-27 |
| AU2008350937A1 (en) | 2009-08-27 |
| EP2463362A1 (en) | 2012-06-13 |
| BRPI0819774A2 (pt) | 2014-10-14 |
| US8231880B2 (en) | 2012-07-31 |
| EP2463362B1 (en) | 2017-11-08 |
| JP2015083007A (ja) | 2015-04-30 |
| WO2009105084A8 (en) | 2010-10-07 |
| AU2008350937B2 (en) | 2014-10-09 |
| US20100260799A1 (en) | 2010-10-14 |
| CN102131920B (zh) | 2013-11-06 |
| KR101614369B1 (ko) | 2016-04-21 |
| CN102131920A (zh) | 2011-07-20 |
| EP2220217A2 (en) | 2010-08-25 |
| ZA201003895B (en) | 2011-04-28 |
| MX2010005860A (es) | 2010-06-22 |
| CA2707029A1 (en) | 2009-08-27 |
| WO2009105084A3 (en) | 2009-12-30 |
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