KR102638074B1 - 재조합 단백질을 고분비 수율로 생산하기 위한 조성물 및 방법 - Google Patents
재조합 단백질을 고분비 수율로 생산하기 위한 조성물 및 방법 Download PDFInfo
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- KR102638074B1 KR102638074B1 KR1020197029626A KR20197029626A KR102638074B1 KR 102638074 B1 KR102638074 B1 KR 102638074B1 KR 1020197029626 A KR1020197029626 A KR 1020197029626A KR 20197029626 A KR20197029626 A KR 20197029626A KR 102638074 B1 KR102638074 B1 KR 102638074B1
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Abstract
본원의 개시내용은 재조합 단백질을 생산하기 위한 방법, 및 상기 방법에 사용되고 이에 의해 생산되는 조성물에 관한 것이다. 구체적으로, 본원의 개시내용은 고분비 수율로 재조합 단백질을 생산하기 위한 방법에 관한 것이고, 본원에 제공된 조성물은 사카로마이세스 세레비지애 ( Saccharomyces cerevisiae ) 및 비-αMF 신호 펩타이드의 α-교배 인자 (αMF)의 리더 펩타이드를 포함하는 재조합 분비 신호와 작동가능하게 연결되는 단백질을 암호화하는 폴리뉴클레오타이드 서열을 포함하는 발현 작제물, 재조합 벡터, 재조합 숙주 세포를 포함한다.
Description
관련 출원에 대한 상호 참조
본 출원은 2017년 3월 10일자로 출원된 미국 가출원 번호 제62/470,144호의 이점을 주장하며, 이의 개시내용은 본원에 참조로 포함된다.
본 발명의 기술분야
본원의 개시내용은 재조합 단백질을 생산하기 위한 방법뿐만 아니라, 상기 방법에 사용되고 이에 의해 생산되는 조성물에 관한 것이다. 구체적으로, 본원의 개시내용은 재조합 단백질을 고분비 수율로 생산하기 위한 방법뿐만 아니라, 상기 방법에 사용되는 발현 작제물, 재조합 벡터, 재조합 숙주 세포 및 발효에 관한 것이다.
연구, 산업적 또는 치료학적 목적을 위해 요구되는 단백질 (예를 들어, 효소, 백신, 호르몬 및 생약제학적 단백질)은 재조합 숙주 세포에서 산업적으로 생산된다. 효모, 특히, 출아 효모는 상기 응용을 위해 선호되는 진핵 숙주 유기체이다. 효모 세포는 저렴한 배지에서 높은 세포 밀도로 신속하게 성장하고 단백질 폴딩 및 해독 후 변형(예를 들어, 단백질 가수분해 성숙화, 디설파이드 결합 형성, 인산화, O- 및 N-연결된 당화)을 위한 세포 기구를 포함한다. 재조합 단백질을 생산하기 위해 가장 통상적으로 사용되는 효모 종은 사카로마이세스 세레비지애 (Saccharomyces cerevisiae ), 피키아 파스토리스 ( Pichia pastoris ), 한세눌라 폴 리모르파 ( Hansenula polymorpha ), 및 클루이베로마이세스 락티스 ( Kluyveromyces lactis)를 포함한다. 이들 중에서, 피키아 파스토리스는 재조합 단백질이 보다 큰 (예를 들어, 산업적) 규모로 생산되어야만 하는 응용에 특히 적합한데 그 이유는 고밀도 세포 성장을 성취할 수 있기 때문이다.
재조합 숙주 세포에서 재조합 단백질의 산업적 규모의 생산은 상기 재조합 단백질이 세포로부터 분비되는 경우 용이해지는데 그 이유는 분비된 단백질이 온전한 세포로부터 용이하게 분리되기 때문이고, 세포 용해 및 세포 잔해물로부터 단백질의 후속적 분리가 필요 없다. 피키아 파스토리스는 분비된 재조합 단백질의 생산에 특히 적합한데 그 이유는 이것이 최소 염 배지에서 성장할 수 있어 이는 낮은 전도율에서 여과 및 크로마토그래피를 통해 분리된 단백질의 단리를 가능하게 하기 때문이고 피키아 파스토리스는 고유하게 상대적으로 적은 생성물 (즉, 소형 단백질)을 분비하고, 이는 분비된 재조합 단백질의 단리 및 정제를 추가로 촉진시키기 때문이다.
분비된 재조합 단백질의 생산을 위해 사용되는 재조합 숙주 세포는 이상적으로 대량의 재조합 단백질을 생산하고 생산되는 재조합 단백질의 대부분을 분비한다. 전자는 전형적으로 예를 들어, 재조합 숙주 세포 내로 가공되고 재조합 단백질을 암호화하는 폴리뉴클레오타이드 서열을 코돈 최적화하고, 상기 폴리뉴클레오타이드 서열의 전사를 강한 프로모터 및 효과적인 종결자의 제어 하에 있도록 하고, 적합한 리보스 결합 부위를 도입함에 의해 해독을 최적화하고, 재조합 숙주 세포 내 폴리뉴클레오타이드 서열의 카피수를 증가시키는 (예를 들어, 특정 폴리뉴클레오타이드 서열의 2개 이상의 카피를 포함하는 숙주 세포를 가공함에 의해)것과 같은 당업계에 널리 공지된 전략을 사용함에 의해 성취된다. 이들 전략은 그러나 이들의 효과에서 고유 한계에 도달하는 경향이 있는데 그 이유는 높은 카피수가 유전학적으로 재조합 숙주 세포를 불안정화시키고, 강한 프로모터가 재조합 숙주 세포가 적당히 폴딩시키고/시키거나 분비할 수 있는 것보다 높은 수준의 재조합 단백질을 생성하기 때문이다(문헌참조: Damasceno et al. [2012] Appl Microbiol Biotechnol 93:31-39; Parekh et al. [1995] Protein Expr Purif. 6(4):537-45; Zhu et al. [2009]- J Appl Microbiol 107:954-963; Liu et al. [2003] Protein Expr. Purif. 30:262-274). 결과로서, 재조합 단백질의 수율은 폴딩되지 않거나 잘못 폴딩된 재조합 단백질이 재조합 숙주 세포 내부에 축적하고 재조합 숙주 세포가 분자 스트레스 반응을 활성화시키기 때문에 정체기에 이르거나 심지어 감소하는 경향이 있다 (예를 들어, 폴딩되지 않은 단백질 반응 [UPR] 또는 ER-연합된 단백질 분해 경로 [ERAD] (문헌참조: Hohenblum et al. [2004] Biotechnol Bioeng. 12:367-375; Vassileva et al. [2001] J Biotechnol. 12:21-35; Inan et al. [2006] Biotechnol Bioeng. 12:771-778; Zhu et al. [2009] J Appl Microbiol. 12(3):954-963). 실제로, 샤페론 단백질 또는 주요 UPR 전사 조절인자 (Hac1p)의 상향조절은 UPR의 효과를 감소시키고 재조합 단백질 수율을 부스팅하는 것으로 나타났다(문헌참조: Zhang et al. [2006] Biotechnol Prog. 12:1090-1095; Lee et al. [2012] Process Biochem. 12:2300-2305; Valkonen et al. [2003] Appl Environ Microbiol. 12:6979-6986). 그러나, 상기 대책은 혼성 결과를 생성하였고(문헌참조: Guerfal et al. [2010] Microb Cell Fact.12:49) 재조합 숙주 세포의 분비 경로의 포화를 여전히 완전히 제거하지 못한다(문헌참조: Inan et al. [2006] Biotechnol Bioeng.12:771-778). 따라서, 재조합 숙주 세포의 분비 기구의 능력은 재조합 단백질의 생산을 위한 주요 병목으로 남아있다.
따라서, 재조합 숙주 세포에 대한 과발현의 부정적인 영향을 완화시키면서 목적하는 재조합 단백질의 증가된 발현을 가능하게 하는 방법 및 조성물이 필요하다.
도 1은 재조합 단백질을 고분비 수율로 생산하기 위한 방법의 흐름도이다.
도 2는 사카로마이세스 세레비지애 (*프로-αMF(sc))의 α-교배 인자의 리더 펩타이드 및 신호 펩타이드의 기능성 변이체를 포함하는 N-말단 재조합 분비 신호에 작동가능하게 연결된 실크-유사 단백질을 암호화하는 폴리뉴클레오타이드 서열을 포함하는 재조합 벡터의 도해적 맵이다. 사용된 다양한 신호 펩타이드 및 재조합 분비 신호에 대한 아미노산 서열은 표 A 및 B에 제공된다.
도 3 내지 6은 는 ELISA에 의해 분석되는 바와 같이 다양한 피키아 파스토리 스 재조합 숙주 세포에 의해 생성된 재조합 실크 유사 단백질의 세포외 (분비) 수율을 보여준다.
도 7은 본 발명의 구현예에 따라 재조합 분비 신호를 갖는 폴리펩타이드를 발현하기 위해 발현 작제물을 포함하는 재조합 벡터의 다이아그램이다.
도 8은 다양한 재조합 분비 신호를 갖는 재조합 알파-아밀라제를 발현하도록 형질전환된 피키아 파스토리스로부터 알파-아밀라제의 분비 수준을 도해한다.
도 9는 다양한 재조합 분비 신호를 갖는 재조합 형광성 단백질을 발현하도록 형질전환된 피키아 파스토리스로부터 형광성 단백질의 분비 수준을 도해한다.
상기 도면은 단지 도해 목적을 위해 본원의 개시내용의 다양한 구현예를 도시한다. 당업자는 본원에 도해된 구조 및 방법의 대안적 구현예가 본원에 기재된 원리로부터 벗어나는 것 없이 사용될 수 있다는 것을 하기의 논의로부터 용이하게 인지할 것이다.
도 2는 사카로마이세스 세레비지애 (*프로-αMF(sc))의 α-교배 인자의 리더 펩타이드 및 신호 펩타이드의 기능성 변이체를 포함하는 N-말단 재조합 분비 신호에 작동가능하게 연결된 실크-유사 단백질을 암호화하는 폴리뉴클레오타이드 서열을 포함하는 재조합 벡터의 도해적 맵이다. 사용된 다양한 신호 펩타이드 및 재조합 분비 신호에 대한 아미노산 서열은 표 A 및 B에 제공된다.
도 3 내지 6은 는 ELISA에 의해 분석되는 바와 같이 다양한 피키아 파스토리 스 재조합 숙주 세포에 의해 생성된 재조합 실크 유사 단백질의 세포외 (분비) 수율을 보여준다.
도 7은 본 발명의 구현예에 따라 재조합 분비 신호를 갖는 폴리펩타이드를 발현하기 위해 발현 작제물을 포함하는 재조합 벡터의 다이아그램이다.
도 8은 다양한 재조합 분비 신호를 갖는 재조합 알파-아밀라제를 발현하도록 형질전환된 피키아 파스토리스로부터 알파-아밀라제의 분비 수준을 도해한다.
도 9는 다양한 재조합 분비 신호를 갖는 재조합 형광성 단백질을 발현하도록 형질전환된 피키아 파스토리스로부터 형광성 단백질의 분비 수준을 도해한다.
상기 도면은 단지 도해 목적을 위해 본원의 개시내용의 다양한 구현예를 도시한다. 당업자는 본원에 도해된 구조 및 방법의 대안적 구현예가 본원에 기재된 원리로부터 벗어나는 것 없이 사용될 수 있다는 것을 하기의 논의로부터 용이하게 인지할 것이다.
정의
달리 정의되지 않는 경우, 본원에서 사용된 모든 기술적 및 과학적 용어는 본원의 개시내용이 속하는 기술 분야의 통상의 기술자에 의해 통상적으로 이해되는 바와 동일한 의미를 갖는다.
용어 "a" 및 "an" 및 "the" 및 본원에 사용된 바와 같은 유사 용어는 본원에 달리 지적되거나 문맥에 의해 명백히 반박되지 않는 경우 단수 및 복수 둘 다를 언급한다.
아미노산은 이들의 단일-문자 코드 또는 이들의 3문자 코드에 의해 언급될 수 있다. 단일-문자 코드, 아미노산 명칭 및 3-문자 코드는 다음과 같다: G - 글라이신 (Gly), P - 프롤린 (Pro), A - 알라닌 (Ala), V - 발린 (Val), L - 류신 (Leu), I - 이소류신 (Ile), M - 메티오닌 (Met), C - 시스테인 (Cys), F - 페닐알라닌 (Phe), Y - 티로신 (Tyr), W - 트립토판 (Trp), H - 히스티딘 (His), K - 라이신 (Lys), R - 아르기닌 (Arg), Q - 글루타민 (Gln), N - 아스파라긴 (Asn), E - 글루탐산 (Glu), D - 아스파르트산 (Asp), S - 세린 (Ser), T - 트레오닌 (Thr).
본원에 사용된 바와 같은 용어 "기능성 변이체"는 고유 단백질과 조성에 있어서 상이한 단백질을 언급하고, 여기서, 기능성 성질은 고유 단백질 성질의 10% 이내에서 보존된다. 일부 실시 양태에서, 기능성 변이체와 고유 단백질 간의 차이는 주요 아미노산 서열 (예를 들어, 하나 이상의 아미노산은 제거되거나, 삽입되거나 치환된다) 또는 해독 후 변형 (예를 들어, 당화, 인산화)에 있을 수 있다. 아미노산 삽입은 단일 또는 다중 아미노산의 내부 서열 삽입뿐만 아니라 N-말단 및/또는 C-말단 융합부를 포함할 수 있다. 아미노산 치환은 비-보존성 및 보존성 치환을 포함하고, 여기서, 보존성 아미노산 치환은 당업계에 널리 공지되어 있다(문헌참조: 예를 들어, Creighton (1984) Proteins.W.H.Freeman and Company (Eds)). 일부 실시 양태에서, 기능성 변이체 및 고유 단백질은 적어도 80%, 적어도 85%, 적어도 90%, 적어도 95%, 또는 적어도 99%의 아미노산 또는 뉴클레오타이드 서열 동일성을 갖는다.
본원에 사용된 바와 같은 핵산 또는 아미노산 서열과 관련하여 용어 "동일성" 또는 "동일한"은 서열이 최대 상응성을 위해 정렬되는 경우 동일한 2개의 서열 내 뉴클레오타이드 또는 아미노산 잔기를 언급한다. 상기 응용에 의존하여, "동일성" 퍼센트는 비교되는 서열 영역 상에 존재할 수 있거나 (즉, 서브서열 [예를 들어, 기능성 도메인 상에]) 대안적으로 서열의 전장에 걸쳐 존재할 수 있다. "영역"은 적어도 9, 20, 24, 28, 32, 또는 36개 뉴클레오타이드, 또는 적어도 6개 아미노산의 연속 스트레치인 것으로 고려된다. 서열 비교를 위해, 전형적으로 하나의 서열은 시험 서열이 이와 비교되는 참조 서열로서 작용한다. 서열 비교 알고리즘을 사용하는 경우, 시험 및 참조 서열은 컴퓨터에 입력되고 필요한 경우 서브서열 좌표가 지정되고 서열 알고리즘 프로그램 파라미터가 지정된다. 이어서, 서열 비교 알고리즘은 지정된 프로그램 파라미터를 기준으로 참조 서열과 상대적으로 시험 서열(들)에 대한 서열 동일성 퍼센트를 계산한다. 비교를 위한 서열의 최적의 정렬은 예를 들어, Smith & Waterman, Adv.Appl.Math.2:482 (1981)의 국소 상동성 알고리즘, Needleman & Wunsch, J. Mol. Biol. 48:443 (1970)의 상동성 정렬 알고리즘, Pearson & Lipman, Proc. Nat'l.Acad. Sci. USA 85:2444 (1988)의 유사성 방법에 의한 조사, 이들 알고리즘(GAP, BESTFIT, FASTA, 및 TFASTA(기관: Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, Wis.))의 컴퓨터 수행, 또는 육안 조사(문헌참조: 일반적으로 Ausubel et al., infra)에 의해 수행될 수 있다. 서열 동일성 및 서열 유사성 퍼센트를 결정하기 위해 적합한 알고리즘의 하나의 예는 BLAST 알고리즘이다(문헌참조: 예를 들어, Altschul et al. [1990] J. Mol. Biol. 215:403-410; Gish & States.[1993] Nature Genet.3:266-272; Madden et al. [1996] Meth.Enzymol.266:131-141; Altschul et al. [1997] Nucleic Acids Res.25:3389-3402; Zhang 7 Madden.[1997] Genome Res.7:649-656). BLAST 분석을 수행하기 위한 소프트웨어는 기관 (National Center for Biotechnology Information)을 통해 공개적으로 가용하다. 상기 소프트웨어는 또한 폴리펩타이드 서열 내 또는 상기 서열의 도메인 내에서 발견되는 임의의 특정 아미노산의 몰 퍼센트를 결정하기 위해 사용될 수 있다. 당업자는 상기 퍼센트가 또한 조사 및 수동 계산을 통해 결정될 수 있음을 인지할 것이다.
용어 "포함하는", "포함한다", "갖는 (having)", "갖는다 (has)", "와 함께 (with)", 또는 이의 변형체는 용어 "포함하는"과 유사한 방식으로 포괄적인 것으로 의도된다.
본원에 사용된 바와 같은 용어 "미생물 (microbe)"은 미생물 (microorganism)을 언급하고 단세포 유기체를 언급한다. 본원에 사용된 바와 같은 용어는 모든 세균, 모든 고세균, 단세포 원생생물, 단세포 동물, 단세포 식물, 단세포 진균류, 단세포 조류, 모든 원생동물, 및 모든 색조류계를 포함한다.
용어 본원에 사용된 바와 같은 "고유"는 이의 천연의 비변형된 상태에서 발견되는 것을 언급한다.
본원에 사용된 바와 같은 용어 "작동가능하게 연결된"은 단백질을 암호화하는 폴리뉴클레오타이드 서열 또는 단백질과 연속으로 연결된 폴리뉴클레오타이드 또는 아미노산 서열, 및 단백질을 암호화하는 폴리뉴클레오타이드 서열과 트랜스로 또는 일정 거리에서 작용하고 단백질을 암호화하는 폴리뉴클레오타이드 또는 단백질의 전사, 해독, 폴딩, 분비 또는 다른 기능성 양상을 제어하는, 폴리뉴클레오타이드 또는 아미노산 서열을 언급한다.
용어 "임의의" 또는 "임의로"는 특정 특성 또는 구조가 존재하거나 존재하지 않을 수 있거나, 이벤트 또는 상황이 존재하거나 존재하지 않을 수 있음을 의미하고, 상기 기재가 특정 특성 또는 구조가 존재하는 상황 및 상기 특성 또는 구조가 존재하는 상황, 또는 이벤트 또는 상황이 존재하는 상황 및 상기 이벤트 또는 상황이 일어나지 않는 상황을 포함한다.
본원에 사용된 바와 같은 용어 "단백질"은 기능성 구조물이 없는 폴리펩타이드 및 활성 구조로 폴딩되는 폴리펩타이드 둘 다를 언급한다.
본원에 사용된 바와 같은 용어 "재조합 단백질"은 재조합 숙주 세포에서 생성되는 단백질을 언급하거나, 재조합 핵산으로부터 합성되는 단백질을 언급한다.
본원에 사용된 바와 같은 용어 "재조합 숙주 세포"는 재조합 핵산을 포함하는 숙주 세포를 언급한다.
본원에 사용된 바와 같은 용어 "재조합 핵산"은 이의 자연 발생 환경으로부터 제거된 핵산, 또는 이것이 자연에서 발견되는 경우 핵산에 인접하거나 근접한 핵산 전부 또는 일부와 연합되지 않은 핵산, 또는 이것이 자연적으로 연결되지 않은 핵산에 작동가능하게 연결된 핵산, 또는 천연적으로 존재하지 않는 핵산, 또는 자연에서 핵산에서 발견되지 않는 변형 (예를 들어, 삽입, 결실 또는 인간 중재에 의해 인공적으로 도입된 점 돌연변이)을 함유하는 핵산, 또는 이종성 부위에서 염색체로 통합된 핵산을 언급한다. 상기 용어는 클로닝된 DNA 단리물 및 화학적으로 합성된 뉴클레오타이드 유사체를 포함하는 핵산을 포함한다.
본원에 사용된 바와 같은 용어 "재조합 분비 신호"는 신호 펩타이드와 리더 펩타이드의 비-천연적 조합을 포함하는 분비 신호를 언급한다.
본원에 사용된 바와 같은 용어 "재조합 벡터"는 이것이 연결되는 또 다른 핵산을 수송할 수 있는 핵산 분자를 언급한다. 상기 용어는 일반적으로 추가의 DNA 분절이 연결될 수 있는 환형 이중 가닥 DNA 루프, 및 폴리머라제 연쇄 반응 (PCR)에 의한 증폭으로부터 또는 제한 효소를 사용한 플라스미드의 처리로부터 비롯된 것들과 같은 선형 이중 가닥 분자를 언급하는 "플라스미드"를 포함한다. 벡터의 다른 비제한적인 예는 박테리오파아지, 코스미드, 세균 인공 염색체 (BAC), 효모 인공 염색체 (YAC), 및 바이러스 벡터 (즉, 추가의 DNA 분절이 연결된 완전하거나 부분적인 바이러스 게놈)를 포함한다. 특정 벡터는 이들이 도입된 재조합 숙주 세포에서 자가 복제할 수 있다 (예를 들어, 세포에서 작용하는 복제 오리진을 갖는 벡터). 도입 시 다른 벡터는 재조합 숙주 세포의 게놈에 통합될 수 있고 이에 의해 세포 게놈과 함께 복제된다.
본원에 사용된 바와 같은 용어 "분비된 재조합 단백질"은 재조합 단백질을 생성하는 재조합 숙주 세포의 세포막 및/또는 세포 벽을 거쳐 배출되는 재조합 단백질을 언급한다.
본원에 사용된 바와 같은 용어 "분비 수율"은 숙주 세포를 포함하는 발효에 공급되는 고정된 탄소 양을 기반으로 숙주 세포에 의해 생산되는 분비된 단백질의 양을 언급한다.
본원에 사용된 바와 같은 용어 "총 수율"은 숙주 세포를 포함하는 발효에 공급되는 고정된 탄소 양을 기반으로 숙주 세포에 의해 생산되는 총 단백질의 양을 언급한다.
본원에 사용된 바와 같은 용어 "절두된"은 본래의 단백질 보다 길이가 짧은 단백질 서열을 언급한다. 일부 실시 양태에서, 절두된 단백질은 본래의 단백질 길이의 10% 초과, 또는 20% 초과, 또는 30% 초과, 또는 40% 초과, 또는 50% 초과, 또는 60% 초과, 또는 70% 초과, 또는 80% 초과, 또는 90% 초과일 수 있다.
예시적 방법 및 재료는 하기에 기재되어 있지만, 본원에 기재된 것들과 유사하거나 동등한 방법 및 재료가 또한 본 발명의 수행에서 사용될 수 있고 당업자에게 자명할 것이다. 본원에서 언급된 모든 간행물 및 기타 참조 문헌은 그 내용 전체가 참조로 포함된다. 상충하는 경우, 정의를 포함하는 본 명세서가 우선할 것이다. 상기 물질, 방법 및 실시예들은 단지 예시일 뿐, 본 발명의 범위를 한정하려는 것은 아니다.
값의 범위가 언급될 때마다, 상기 범위는 명백히 기재된 것과 같이 상기 범위 내 속하는 모든 값을 포함하고, 상기 범위를 경계하는 값을 더 포함한다. 따라서, "X 내지 Y"의 범위는 X와 Y 사이에 속하는 모든 값을 포함하고 X 및 Y를 포함한다.
재조합 단백질을
고분비
수율로 생산하기 위한 조성물 및 방법
본원에 제공된 것은 발현 작제물, 재조합 벡터, 재조합 숙주 세포 및 발효, 및 재조합 단백질을 고분비 수율로 생산하기 위해 상기 발현 작제물, 재조합 벡터, 재조합 숙주 세포 및 발효를 사용하는 방법이다.
본원에 제공되는 조성물 및 방법의 이점은 이들이 대량의 재조합 단백질을 생산하기 위해 저렴한 수단을 제공함을 포함한다. 대량은 이들의 분비 경로를 통해 재조합 단백질을 분비하는 재조합 숙주 세포를 사용하여 수득된다. 재조합 단백질의 상기 분비는 a) 재조합 단백질의 세포내 축적으로부터의 독성을 회피하고; b) 세포 파쇄, 세포 성분으로부터의 분리 및 단백질의 재폴딩 공정을 제외시킴에 의해 정제를 단순화하고; c) 재조합 단백질의 활성/기능에 중요할 수 있는 해독 후 변형을 갖는 적당히 폴딩된 재조합 단백질을 제공한다.
발현
작제물
본원에 제공된 재조합 분비 신호에 작동가능하게 연결된 단백질을 암호화하는 폴리뉴클레오타이드 서열을 포함하는 발현 작제물이 본원에 제공된다. 재조합 분비 신호는 전형적으로 단백질의 N-단말에 작동가능하게 연결된다.
재조합 분비 신호
분비되도록 하기 위해서는, 단백질은 이를 생산하는 세포의 세포내 분비 경로를 통해 이동해야만 한다. 상기 단백질은 N-말단 분비 신호를 통해, 또 다른 세포 지정장소로의 이동 보다는 상기 경로로 지시된다. 최소로, 분비 신호는 신호 펩타이드를 포함한다. 신호 펩타이드는 전형적으로 N-말단 염기성 아미노산 및 C-말단 극성 아미노산에 의해 플랭킹된 13 내지 36개의 대부분 소수성인 아미노산으로 이루어진다. 신호 펩타이드는 발생 초기 단백질을 세포질로부터 ER의 루멘으로 해독과 동시에 또는 해독 후의 이동을 매개하는 신호 인지 입자 (SRP) 또는 다른 수송 단백질 (예를 들어, SND, GET)과 상호작용한다. ER에서, 신호 펩타이드는 전형적으로 절단 제거하고 단백질은 폴딩하고 해독 후 변형을 진행한다. 이어서, 상기 단백질은 ER로부터 골지체로 전달되고, 이어서 분비 소포체 및 세포 외부로 전달된다. 신호 펩타이드에 추가로, 본래에 분비를 위해 지정된 발생 초기 단백질의 서브세트는 리더 펩타이드도 포함하는 분비 신호를 갖고 있다. 리더 펩타이드는 전형적으로, 하전에 의해 차단된 소수성 아미노산 또는 극성 아미노산으로 이루어진다. 이론에 국한되는 것 없이, 리더 펩타이드는 수송을 서행시켜 단백질의 적당한 폴딩을 보장하고/하거나 ER로부터 골지체로의 단백질의 수송을 촉진시키고, 상기 리더 펩타이드는 전형적으로 절단 제거되는 것으로 사료된다.
세포로부터 분비되는 단백질의 양은 단백질 간에 상당히 다양하고, 부분적으로 이의 발생 초기 상태에서 단백질에 작동가능하게 연결된 분비 신호에 의존한다. 다수의 분비 신호는 당업계에 공지되어 있고, 일부는 통상적으로 분비된 재조합 단백질의 생산을 위해 사용된다. 이들 중에서 두드러진 것은 사카로마이세스 세레비지애 (Saccharomyces cerevisiae )의 α-교배 인자 (αMF)의 분비 신호이고, 이것은 N-말단 19-아미노산 신호 펩타이드 (또한 본원에서 프리-αMF(sc)로서 언급되는)에 이어서 70-아미노산 리더 펩타이드로 이루어진다 (또한 본원에서 프로-αMF(sc)로서 언급됨; 서열번호: 1). 사카로마이세스세레비지애의 αMF (또한 본원에서 프리-αMF(sc)/프로-αMF(sc)로서 언급되는)의 분비 신호에서 프로-αMF(sc) (서열번호 115)의 내포는 단백질의 고분비 수율을 성취하기 위해 중요함을 입증하였다(문헌참조: 예를 들어, 문헌[Fitzgerald & Glick [2014] Microb Cell Fact 28;13(1):125; Fahnestock et al. [2000] J Biotechnol 74(2):105)]를 참조한다. 프리-αMF(sc) 이외의 다른 신호 펩타이드에 프로-αMF(sc) 또는 이의 기능성 변이체의 추가는 또한 재조합 단백질의 분비를 성취하는 수단으로서 탐구되었지만 다양한 정도의 효과를 보여주었고, 특정 재조합 숙주 세포에서 특정 재조합 단백질에 대한 분비를 증가시키지만 다른 재조합 단백질에 대한 분비에 효과가 없거나 분비를 감소시킨다(문헌참조: Fitzgerald & Glick.[2014] Microb Cell Fact 28;13(1):125; Liu et al. [2005] Biochem Biophys Res Commun.326(4):817-24 ; Obst et al. [2017] ACS Synth Biol. 2017 Mar 2).
본원에 제공된 발명은 다양한 분비 수율의 재조합 단백질을 제공하는 프리-αMF(sc) 이외의 특정 신호 펩타이드와 조합하여 고유 프로-αMF(sc)(본원에서 *프로-αMF(sc)로 지칭됨)의 기능성 변이체를 포함하는 재조합 분비 신호의 발명자에 의한 식별에 기초한다. 일부 실시 양태에서, 재조합 분비 신호는 종래 기술(예를 들어, 프리-OST1(sc) / 프로-αMF(sc); [Fitzgerald & Glick. [2014] Microb Cell Fact 28;13(1):125; Liu et al. [2005] Biochem Biophys Res Commun. 326(4):817-24 ; Obst et al. [2017] ACS Synth Biol. 2017 Mar 2] 참조)에서 사카로마이세스 세레비지애의 α-교배 인자 (αMF)의 분비 신호 및/또는 재조합 분비 신호로 달성되는 것보다 더 크게 재조합 단백질 분비 수율을 제공한다. 다른 양태에서, 재조합 분비 신호는 사카로마이세스 세레비지애의 α-교배 인자 (αMF)의 분비 신호로 달성되는 것보다 더 적은 재조합 단백질의 분비 수율을 제공한다.
따라서, 다양한 실시 양태에서, 본원에 제공된 발현 작제물은 리더 펩타이드와 신호 펩타이드를 포함하는 재조합 분비 신호에 작동가능하게 연결된 단백질을 암호화하는 폴리뉴클레오타이드 서열을 포함하고, 여기서 리더 펩타이드는 프로-αMF(sc)(서열번호: 1) 또는 서열번호 1과 적어도 80% 아미노산 서열 동일성을 갖는 기능성 변이체이고, 신호 펩타이드는 프리-αMF(sc)를 포함하지 않는다.
일부 실시 양태에서, 기능성 변이체는 하나 또는 두개의 치환된 아미노산을 포함하는 고유 프로-αMF(sc)이다. 일부 실시 양태에서, 기능성 변이체는 *프로-αMF이다 (서열번호 2). 일부 실시 양태에서, 상기 기능성 변이체는 하기 서열번호 1과 적어도 85%, 적어도 90%, 적어도 95%, 또는 적어도 99%의 아미노산 서열 동일성을 갖는다. 일부 실시 양태에서, 상기 기능성 변이체는 αMF_no_EAEA 또는 αMF△ 또는 αMF△_no_Kex (문헌참조: Obst et al. [2017] ACS Synth Biol. 2017 Mar 2)이다.
일부 실시 양태에서, 표 1로부터 선택된 신호 펩타이드 또는 표 1로부터 선택된 신호 펩타이드와 적어도 80% 아미노산 서열 동일성을 갖는 기능성 변이체이다. 일부 실시 양태에서, 기능성 변이체는 1개 또는 2개의 치환된 아미노산을 포함하는 표 1로부터 선택된 신호 펩타이드이다. 일부 상기 실시 양태에서, 기능성 변이체는 표 1로부터 선택된 신호 펩타이드와 적어도 85%, 적어도 90%, 적어도 95%, 또는 적어도 99%의 아미노산 서열 동일성을 갖는다. 일부 실시 양태에서, 신호 펩타이드는 발생 초기 재조합 단백질의 해독 후 ER로의 이동을 매개한다(즉, 단백질 합성은 이동을 진행시켜 발생 초기 재조합 단백질이 ER로 이동하기 전 세포 세포질에 존재하도록 한다). 다른 실시 양태에서, 신호 펩타이드는 발생 초기 재조합 단백질의 해독과 동시에 ER로의 이동을 매개한다 (즉, 단백질 합성 및 ER로의 이동은 동시에 일어난다). 해독과 동시의 ER로의 이동을 매개하는 신호 펩타이드를 사용하는 이점은 신속한 폴딩 경향이 있는 재조합 단백질이 ER로의 이동 및 이에 따른 분비를 방해하는 형태를 가정하는 것이 방지된다는 것이다.
표 1 - 신호 펩타이드
따라서, 일부 실시 양태에서, 발현 작제물은 표 2로부터 선택되는 재조합 분비 신호에 작동가능하게 연결된 단백질을 암호화하는 폴리뉴클레이타이드 서열을 포함하거나 표 2로부터 선택되는 재조합 분비 신호와 적어도 80% 아미노산 서열 동일성을 갖는 기능성 변이체이다. 일부 실시 양태에서, 기능성 변이체는 표 2로부터 선택되는 재조합 분비 신호와 적어도 85%, 적어도 90%, 적어도 95%, 또는 적어도 99% 아미노산 서열 동일성을 갖는다.
일부 실시 양태에서, 본원에 제공된 발현 작제물은 다중 (예를 들어, 2, 3, 4, 5, 등) 카피로 폴리뉴클레오타이드 서열을 포함한다. 이러한 일부 실시 양태에서, 폴리뉴클레오타이드 서열은 동일하다. 다른 이러한 실시 양태에서, 적어도 2개의 폴리뉴클레오타이드 서열은 동일하지 않다. 적어도 2개의 폴리뉴클레오타이드 서열은 동일하지 않은 실시 양태에서, 적어도 2개의 폴리뉴클레오타이드 서열은 단백질 및/또는 재조합 분비 신호 및/또는 이들이 암호화하는 선택적 태그 펩타이드 및 폴리펩타이드(이하 참조)에서 서로 상이할 수 있다.
표 2 - 재조합 분비 신호
재조합 단백질
본원에 제공된 발현 작제물에 포함되는 폴리뉴클레오타이드 서열에 의해 암호화된 단백질은 임의의 단백질일 수 있다.
일부 실시 양태에서, 단백질은 실크 또는 실크 유사 단백질이다. 상기 실크 또는 실크 유사 단백질은 전장 또는 절두된 본래의 실크 단백질 또는 전장 또는 절두된 본래의 실크 단백질의 기능성 변이체의 막대한 어레이로부터 선택될 수 있거나 본래의 실크 단백질 또는 실크 단백질의 기능성 변이체의 도메인을 포함한다. 추정 고유 실크 단백질은 관련 용어 (예를 들어, 누에 실크, 스파이더 실크, 스피드로인, 피브로인, MaSp)에 대한 서열 데이터베이스 (예를 들어 GenBank)를 검색하고 임의의 뉴클레오타이드 서열을 아미노산 서열로 해독함에 의해 동정될 수 있다.
일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 누에의 전장 또는 절두된 고유 실크 단백질, 또는 누에의 전장 또는 절두된 고유 실크 단백질의 기능성 변이체이거나, 누에의 고유 실크 단백질의 고유 또는 기능성 변이체의 도메인을 포함한다. 일부 상기 실시 양태에서, 누에는 봄빅스 모리(Bombyx mori)이다 .
일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 스파이더의 전장 또는 절두된 고유 실크 단백질, 또는 스파이더의 전장 또는 절두된 고유 실크 단백질의 기능성 변이체이거나, 스파이더의 고유 실크 단백질의 고유 또는 기능성 변이체의 도메인을 포함한다. 일부 실시 양태에서, 고유 실크 단백질은 오브 위빙 스파이더 (orb weaving spider)의, 메이져 앰풀레이트 스파이더 피브로인 (Major Ampullate spider fibroin) (MaSp, 또한 드래그라인으로 호칭; 예를 들어, MaSp1, MaSp2) 실크 단백질, 마이너 앰풀레이트 스파이더 피브로인 (Minor Ampullate spider fibroin) (MiSp) 실크 단백질, 플라겔리폼 스파이더 피브로인 (Flagelliform spider fibroin) (Flag) 실크 단백질, 액시니폼 스파이더 피브로인 (Aciniform spider fibroin) (AcSp) 실크 단백질, 투불리폼 스파이더 피브로인 (Tubuliform spider fibroin) (TuSp) 실크 단백질, 및 피리폼 스파이더 피브로인 (Pyriform spider fibroin) (PySp) 실크 단백질로 이루어진 군으로부터 선택된다. 일부 실시 양태에서, 스파이더는 아겔레노프시스 아페르타 ( Agelenopsis aperta ), 알리아티푸스 굴로서스 ( Aliatypus gulosus ), 아포노펠마 세마니 ( Aphonopelma seemanni ), 아프토스티쿠스 종(Aptostichus sp.)AS21 7, 압토스티쿠스 종(Aptostichus sp.)AS220 , 아라네우스 디아데마투스 ( Araneus diadematus ), 아라네우스 겜모이데스 ( Araneus gemmoides), 아라네우스 벤트리코서스 ( Araneus ventricosus ), 아르기오페 아모네나 ( Argiope amoena ), 아르기오페 아르겐타타 ( Argiope argentata ), 아르기오페 브루에니키 ( Argiope bruennichi ), 아르기오페 트리파스시아타 ( Argiope trifasciata), 아티포이데스 리베르시 ( Atypoides riversi ), 아비쿨라리아 유루엔시스 ( Avicularia juruensis ), 보트리오시르툼 캘리포르니쿰 ( Bothriocyrtum californicum), 데이노피스 스피노사 ( Deinopis Spinosa ), 디구에티아 카니티에스 (Diguetia canities ), 돌로메데스 테네브로서스 ( Dolomedes tenebrosus ), 유아그루스 키소세우스 ( Euagrus chisoseus ), 유프로스테노프스 아우스트랄리스 (Euprosthenops australis), 가스테라칸타 마모사 ( Gasteracantha mammosa ), 히포킬루스 토렐리 ( Hypochilus thorelli ), 쿠쿨카니아 히베르날리스 ( Kukulcania hibernalis), 라트로덱투스 헤스페루스 ( Latrodectus hesperus ), 메가헥수라 풀바 (Megahexura fulva ), 메테페이라 그란디오사 ( Metepeira grandiosa ), 네필라 안티포디아나 ( Nephila antipodiana ), 네필라 클라바타 ( Nephila clavata ), 네필라 클라비페스 ( Nephila clavipes ), 네필라 마다가스카리엔시스 ( Nephila madagascariensis), 네필라 필리페스 ( Nephila pilipes ), 네필렌기스 크루엔타타 (Nephilengys cruentata ), 파라윅시아 비스트리아타 ( Parawixia bistriata ), 페우세티아 비리단스 ( Peucetia viridans ), 플렉트레우리스 트리스티스 ( Plectreurys tristis), 포에클리오테리아 레갈리스 ( Poecilotheria regalis), 테트라그나타 카우아이엔시스 ( Tetragnatha kauaiensis ), 또는 울로보루스 디베르서스 (Uloborus diversus)로 이루어진 군으로부터 선택된다.
전형적으로, 실크 단백질은 대형 단백질 (>150kDa, >1000 아미노산)이고 이것은 3개의 도메인으로 분해될 수 있다: N-말단 비-반복 도메인 (NTD), 반복 도메인 (REP), 및 C-말단 비-반복 도메인 (CTD). REP는 아미노산 서열의 블록 ("반복 유닛")을 포함하고 이는 길이가 적어도 12개 아미노산이고 완전하게 ("정확한-반복 유닛") 또는 불완전하게 ("준-반복 유닛") 반복하고 길이가 2 내지 10개 아미노산 서열 모티프를 포함할 수 있다 (도 1 참조). REP는 전형적으로 본래의 스파이더 실크 단백질의 약 90%를 차지하고 알라닌-풍부 나노-결정 (<10 nm) 도메인 (가능하게 교호하는 베타 시트로 구성되는) 및 글라이신-풍부 무정형 도메인 (능히 알파-나선 및/또는 베타-턴을 함유하는)으로 어셈블리하고, 이들은 이론에 국한되는 것 없이 각각 스파이더 실크 섬유에 강도 및 유연성을 부여하는 것으로 사료된다. REP의 길이 및 조성물은 상이한 스파이더 실크 단백질 중에서 및 상이한 스파이더 종에 걸쳐 다양한 것으로 공지되어 있고 특이적 성질을 갖는 광범위한 실크 섬유를 생성한다.
일부 실시 양태에서, 실크 또는 실크-유사 단백질은 고유 REP (예를 들어, 1, 2, 3, 4, 5, 6, 7, 8)의 하나 이상의 고유 또는 기능성 변이체, NTD (예를 들어, 0, 1)의 0 이상의 고유 또는 기능성 변이체, 및 고유 CTD (예를 들어, 0, 1)의 0 이상의 고유 또는 기능성 변이체를 포함한다. 일부 실시 양태에서, 실크 또는 실크 유사 단백질은 하나 이상의 NTD를 포함하고 이들 각각은 75 내지 350개 아미노산을 포함한다. 일부 실시 양태에서, 실크 또는 실크 유사 단백질은 하나 이상의 CTD를 포함하고 이들 각각은 75 내지 350개 아미노산을 포함한다. 일부 실시 양태에서, 실크 또는 실크 유사 단백질은 하나 이상의 REP를 포함하고 이들은 반복 유닛들을 포함하고 이들 각각은 60 초과, 100 초과, 150 초과, 200 초과, 250 초과, 300 초과, 350 초과, 400 초과, 450 초과, 500 초과, 600 초과, 700 초과, 800 초과, 900 초과, 1000 초과, 1250 초과, 1500 초과, 1750 초과, 또는 2000 초과; 60 내지 2000, 내지 1750, 내지 1500, 내지 1250, 내지 1000, 내지 900, 내지 800, 내지 700, 내지 600, 내지 500, 내지 450, 내지 400, 내지 350, 내지 300, 내지 250, 내지 200, 내지 150, 또는 내지 100; 100 내지 2000, 내지 1750, 내지 1500, 내지 1250, 내지 1000, 내지 900, 내지 800, 내지 700, 내지 600, 내지 500, 내지 450, 내지 400, 내지 350, 내지 300, 내지 250, 내지 200, 또는 내지 150; 150 내지 2000, 내지 1750, 내지 1500, 내지 1250, 내지 1000, 내지 900, 내지 800, 내지 700, 내지 600, 내지 500, 내지 450, 내지 400, 내지 350, 내지 300, 내지 250, 또는 내지 200; 200 내지 2000, 내지 1750, 내지 1500, 내지 1250, 내지 1000, 내지 900, 내지 800, 내지 700, 내지 600, 내지 500, 내지 450, 내지 400, 내지 350, 내지 300, 또는 내지 250; 250 내지 2000, 내지 1750, 내지 1500, 내지 1250, 내지 1000, 내지 900, 내지 800, 내지 700, 내지 600, 내지 500, 내지 450, 내지 400, 내지 350, 또는 내지 300; 300 내지 2000, 내지 1750, 내지 1500, 내지 1250, 내지 1000, 내지 900, 내지 800, 내지 700, 내지 600, 내지 500, 내지 450, 내지 400, 또는 내지 350; 350 내지 2000, 내지 1750, 내지 1500, 내지 1250, 내지 1000, 내지 900, 내지 800, 내지 700, 내지 600, 내지 500, 내지 450, 또는 내지 400; 400 내지 2000, 내지 1750, 내지 1500, 내지 1250, 내지 1000, 내지 900, 내지 800, 내지 700, 내지 600, 내지 500, 또는 내지 450; 450 내지 2000, 내지 1750, 내지 1500, 내지 1250, 내지 1000, 내지 900, 내지 800, 내지 700, 내지 600, 또는 내지 500; 500 내지 2000, 내지 1750, 내지 1500, 내지 1250, 내지 1000, 내지 900, 내지 800, 내지 700, 또는 내지 600; 600 내지 2000, 내지 1750, 내지 1500, 내지 1250, 내지 1000, 내지 900, 내지 800, 또는 내지 700; 700 내지 2000, 내지 1750, 내지 1500, 내지 1250, 내지 1000, 내지 900, 또는 내지 800; 800 내지 2000, 내지 1750, 내지 1500, 내지 1250, 내지 1000, 또는 내지 900; 900 내지 2000, 내지 1750, 내지 1500, 내지 1250, 또는 내지 1000; 1000 내지 2000, 내지 1750, 내지 1500, 또는 내지 1250; 1250 내지 2000, 내지 1750, 또는 내지 1500; 1500 내지 2000, 또는 내지 1750; 또는 1750 내지 2000 아미노산 잔기를 포함한다.
일부 실시 양태에서, 실크 또는 실크 유사 단백질은 2 초과, 4 초과, 6 초과, 8 초과, 10 초과, 12 초과, 14 초과, 16 초과, 18 초과, 20 초과, 22 초과, 24 초과, 26 초과, 28 초과, 또는 30 초과; 2 내지 30, 내지 28, 내지 26, 내지 24, 내지 22, 내지 20, 내지 18, 내지 16, 내지 14, 내지 12, 내지 10, 내지 8, 내지 6, 또는 내지 4; 4 내지 30, 내지 28, 내지 26, 내지 24, 내지 22, 내지 20, 내지 18, 내지 16, 내지 14, 내지 12, 내지 10, 내지 8, 또는 내지 6; 6 내지 30, 내지 28, 내지 26, 내지 24, 내지 22, 내지 20, 내지 18, 내지 16, 내지 14, 내지 12, 내지 10, 또는 내지 8; 8 내지 30, 내지 28, 내지 26, 내지 24, 내지 22, 내지 20, 내지 18, 내지 16, 내지 14, 내지 12, 또는 내지 10; 10 내지 30, 내지 28, 내지 26, 내지 24, 내지 22, 내지 20, 내지 18, 내지 16, 내지 14, 또는 내지 12; 12 내지 30, 내지 28, 내지 26, 내지 24, 내지 22, 내지 20, 내지 18, 내지 16, 또는 내지 14; 14 내지 30, 내지 28, 내지 26, 내지 24, 내지 22, 내지 20, 내지 18, 또는 내지 16; 16 내지 30, 내지 28, 내지 26, 내지 24, 내지 22, 내지 20, 또는 내지 18; 내지 18 내지 30, 내지 28, 내지 26, 내지 24, 내지 22, 또는 내지 20; 20 내지 30, 내지 28, 내지 26, 내지 24, 또는 내지 22; 22 내지 30, 내지 28, 내지 26, 또는 내지 24; 24 내지 30, 내지 28, 또는 내지 26; 26 내지 30, 또는 내지 28; 28 내지 30의 정확한 반복 및/또는 준-반복 유닛들을 포함하고 이들 각각은 5 kDa 초과, 10 kDa 초과, 20 kDa 초과, 30 kDa 초과, 40 kDa 초과, 50 kDa 초과, 60 kDa 초과, 70 kDa 초과, 80 kDa 초과, 또는 90 kDa초과; 5 kDa 내지 100 kDa, 내지 90 kDa, 내지 80 kDa, 내지 70 kDa, 내지 60 kDa, 내지 50 kDa, 내지 40 kDa, 내지 30 kDa, 내지 20 kDa, 또는 내지 10 kDa; 10 kDa 내지 100 kDa, 내지 90 kDa, 내지 80 kDa, 내지 70 kDa, 내지 60 kDa, 내지 50 kDa, 내지 40 kDa, 내지 30 kDa, 또는 내지 20 kDa; 20 kDa 내지 100 kDa, 내지 90 kDa, 내지 80 kDa, 내지 70 kDa, 내지 60 kDa, 내지 50 kDa, 내지 40 kDa, 또는 내지 30 kDa; 30 kDa 내지 100 kDa, 내지 90 kDa, 내지 80 kDa, 내지 70 kDa, 내지 60 kDa, 내지 50 kDa, 또는 내지 40 kDa; 40 kDa 내지 100 kDa, 내지 90 kDa, 내지 80 kDa, 내지 70 kDa, 내지 60 kDa, 또는 내지 50 kDa; 내지 50 kDa 내지 100 kDa, 내지 90 kDa, 내지 80 kDa, 내지 70 kDa, 또는 내지 60 kDa; 60 kDa 내지 100 kDa, 내지 90 kDa, 내지 80 kDa, 또는 내지 70 kDa; 70 kDa 내지 100 kDa, 내지 90 kDa, 또는 내지 80 kDa; 80 kDa 내지 100 kDa, 또는 내지 90 kDa; 또는 90 kDa 내지 100 kDa의 분자량을 갖는다. 일부 상기 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질 내 2개 이상의 정확한-반복 또는 준-반복 유닛의 배열은 고유하지 않다.
일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 1 초과, 2 초과, 4 초과, 6 초과, 8 초과, 10 초과, 15 초과, 20 초과, 또는 25 초과; 1 내지 30, 내지 25, 내지 20, 내지 15, 내지 10, 내지 8, 내지 6, 내지 4, 또는 내지 2; 2 내지 30, 내지 25, 내지 20, 내지 15, 내지 10, 내지 8, 내지 6, 또는 내지 4; 4 내지 30, 내지 25, 내지 20, 내지 15, 내지 10, 내지 8, 또는 내지 6; 6 내지 30, 내지 25, 내지 20, 내지 15, 내지 10, 또는 내지 8; 8 내지 30, 내지 25, 내지 20, 내지 15, 또는 내지 10; 10 내지 30, 내지 25, 내지 20, 또는 내지 15; 15 내지 30, 내지 25, 또는 내지 20; 20 내지 30, 또는 내지 25; 또는 25 내지 30의 정확한-반복 및/또는 준-반복 유닛을 포함하고 이는 글라이신 풍부하다. 일부 상기 실시 양태에서, 하나 이상의 글라이신 풍부 정확한 반복 및/또는 준-반복 유닛은 4 초과, 6 초과, 8 초과, 10 초과, 12 초과, 15 초과, 18 초과, 20 초과, 25 초과, 30 초과, 40 초과, 50 초과, 60 초과, 70 초과, 80 초과, 90 초과, 100 초과, 150 초과; 4 내지 200, 내지 150, 내지 100, 내지 90, 내지 80, 내지 70, 내지 60, 내지 50, 내지 40, 내지 30, 내지 25, 내지 20, 내지 18, 내지 15, 내지 12, 내지 10, 내지 8, 또는 내지 6; 6 내지 200, 내지 150, 내지 100, 내지 90, 내지 80, 내지 70, 내지 60, 내지 50, 내지 40, 내지 30, 내지 25, 내지 20, 내지 18, 내지 15, 내지 12, 내지 10, 또는 내지 8; 8 내지 200, 내지 150, 내지 100, 내지 90, 내지 80, 내지 70, 내지 60, 내지 50, 내지 40, 내지 30, 내지 25, 내지 20, 내지 18, 내지 15, 내지 12, 또는 내지 10; 10 내지 200, 내지 150, 내지 100, 내지 90, 내지 80, 내지 70, 내지 60, 내지 50, 내지 40, 내지 30, 내지 25, 내지 20, 내지 18, 내지 15, 또는 내지 12; 12 내지 200, 내지 150, 내지 100, 내지 90, 내지 80, 내지 70, 내지 60, 내지 50, 내지 40, 내지 30, 내지 25, 내지 20, 내지 18, 또는 내지 15; 15 내지 200, 내지 150, 내지 100, 내지 90, 내지 80, 내지 70, 내지 60, 내지 50, 내지 40, 내지 30, 내지 25, 내지 20, 또는 내지 18; 18 내지 200, 내지 150, 내지 100, 내지 90, 내지 80, 내지 70, 내지 60, 내지 50, 내지 40, 내지 30, 내지 25, 또는 내지 20; 20 내지 200, 내지 150, 내지 100, 내지 90, 내지 80, 내지 70, 내지 60, 내지 50, 내지 40, 내지 30, 또는 내지 25; 25 내지 200, 내지 150, 내지 100, 내지 90, 내지 80, 내지 70, 내지 60, 내지 50, 내지 40, 또는 내지 30; 30 내지 200, 내지 150, 내지 100, 내지 90, 내지 80, 내지 70, 내지 60, 내지 50, 또는 내지 40; 40 내지 200, 내지 150, 내지 100, 내지 90, 내지 80, 내지 70, 내지 60, 또는 내지 50; 50 내지 200, 내지 150, 내지 100, 내지 90, 내지 80, 내지 70, 또는 내지 60; 60 내지 200, 내지 150, 내지 100, 내지 90, 내지 80, 또는 내지 70; 70 내지 200, 내지 150, 내지 100, 내지 90, 또는 내지 80; 80 내지 200, 내지 150, 내지 100, 또는 내지 90; 90 내지 200, 내지 150, 또는 내지 100; 100 내지 200, 또는 내지 150; 또는 150 내지 200 연속 아미노산을 포함하고 이들은 30% 초과, 40% 초과, 45% 초과, 50% 초과, 55% 초과, 60% 초과, 70% 초과, 또는 80% 초과; 30% 내지 100%, 내지 90%, 내지 80%, 내지 70%, 내지 60%, 내지 55%, 내지 50%, 내지 45%, 또는 내지 40%; 40% 내지 100%, 내지 90%, 내지 80%, 내지 70%, 내지 60%, 내지 55%, 내지 50%, 또는 내지 45%; 45% 내지 100%, 내지 90%, 내지 80%, 내지 70%, 내지 60%, 내지 55%, 또는 내지 50%; 50% 내지 100%, 내지 90%, 내지 80%, 내지 70%, 내지 60%, 또는 내지 55%; 55% 내지 100%, 내지 90%, 내지 80%, 내지 70%, 또는 내지 60%; 60% 내지 100%, 내지 90%, 내지 80%, 또는 내지 70%; 70% 내지 100%, 내지 90%, 또는 내지 80%; 80% 내지 100%, 또는 내지 90%; 또는 90% 내지 100% 글라이신이다.
일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 1 초과, 2 초과, 4 초과, 6 초과, 8 초과, 10 초과, 15 초과, 20 초과, 또는 25 초과; 1 내지 30, 내지 25, 내지 20, 내지 15, 내지 10, 내지 8, 내지 6, 내지 4, 또는 내지 2; 2 내지 30, 내지 25, 내지 20, 내지 15, 내지 10, 내지 8, 내지 6, 또는 내지 4; 4 내지 30, 내지 25, 내지 20, 내지 15, 내지 10, 내지 8, 또는 내지 6; 6 내지 30, 내지 25, 내지 20, 내지 15, 내지 10, 또는 내지 8; 8 내지 30, 내지 25, 내지 20, 내지 15, 또는 내지 10; 10 내지 30, 내지 25, 내지 20, 또는 내지 15; 15 내지 30, 내지 25, 또는 내지 20; 20 내지 30, 또는 내지 25; 또는 25 내지 30의 정확한-반복 및/또는 준-반복 유닛을 포함하고 이는 글라이신 풍부하다. 일부 상기 실시 양태에서, 하나 이상의 알라닌-풍부 정확한-반복 및/또는 준-반복 유닛은 4 초과, 6 초과, 8 초과, 10 초과, 12 초과, 15 초과, 또는 18 초과; 4 내지 20, 내지 18, 내지 15, 내지 12, 내지 10, 내지 8, 또는 내지 6; 6 내지 20, 내지 18, 내지 15, 내지 12, 내지 10, 또는 내지 8; 8 내지 20, 내지 18, 내지 15, 내지 12, 또는 내지 10; 10 내지 18, 내지 15, 또는 내지 12; 12 내지 20, 내지 18, 또는 내지 15; 15 내지 20, 또는 내지 18; 또는 18 내지 20개를 포함하고; 연속 아미노산은 70% 초과, 75% 초과, 80% 초과, 85% 초과, 또는 90% 초과; 70% 내지 100%, 내지 90%, 내지 85%, 내지 80%, 또는 내지 75%; 75% 내지 100%, 내지 90%, 내지 85%, 또는 내지 80%; 80% 내지 100%, 내지 90%, 또는 내지 85%; 85% 내지 100%, 또는 내지 90%; 또는 90% 내지 100%의 알라닌이다.
일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 하나 이상의 글라이신-풍부 정확한-반복 및/또는 준-반복 유닛을 포함하고 이들은 20 내지 100 아미노산 길이이고 4 내지 20 아미노산 길이인 폴리-알라닌-풍부 영역과 연결되어 있다. 일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 5-20%의 폴리-알라닌 영역 (4 내지 20 폴리-알라닌 잔기)을 포함한다. 일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 25-50%의 글라이신을 포함한다. 일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 15-35%의 GGX를 포함하고, 여기서, X는 임의의 아미노산이다. 일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 15-60%의 GPG를 포함한다. 일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 10-40%의 알라닌을 포함한다. 일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 0-20%의 프롤린을 포함한다. 일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 10-50%의 베타-턴을 포함한다. 일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 10-50%의 알파-나선 조성물을 포함한다. 일부 실시 양태에서, 이들 조성물 범위 모두는 동일한 실크 또는 실크 또는 실크 유사 단백질에 적용한다. 일부 실시 양태에서, 이들 조성물 범위의 2개 이상은 동일한 실크 또는 실크 또는 실크 유사 단백질에 적용한다.
일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질의 구조는 베타-시트 구조, 베타-턴 구조 또는 알파-나선 구조를 형성한다. 일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질의 2차, 3차 및 4차 구조는 나노결정 베타-시트 영역, 무정형 베타-턴 영역, 무정형 알파 나선 영역, 비-결정 매트릭스에 매립된 무작위로 공간에 분배된 나노결정 영역, 또는 비-결정 매트릭스에 매립된 무작위로 배향된 나노결정 영역을 갖는다. 일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 고도로 결정성이다. 다른 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 고도로 무정형이다. 일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 결정성 및 무정형 영역 둘 다를 포함한다. 일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 10용적% 내지 40용적%의 결정성 물질을 포함한다.
일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 하나 이상의 정확한 반복 또는 준-반복 유닛을 포함하고 이들은 고유 스파이더 실크 단백질의 반복 유닛과 적어도 80%, 적어도 85%, 적어도 90%, 적어도 95%, 또는 적어도 99%의 아미노산 서열 동일성을 갖는다. 일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 하나 이상의 정확한 반복 또는 준-반복 유닛을 포함하고 이들은 고유 스파이더 실크 드래그라인 실크 단백질의 반복 유닛과 적어도 80%, 적어도 85%, 적어도 90%, 적어도 95%, 또는 적어도 99%의 아미노산 서열 동일성을 갖는다. 일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 하나 이상의 정확한 반복 또는 준-반복 유닛을 포함하고 이들은 고유 MA 드래그라인 실크 단백질의 반복 유닛과 적어도 80%, 적어도 85%, 적어도 90%, 적어도 95%, 또는 적어도 99%의 아미노산 서열 동일성을 갖는다. 일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 하나 이상의 정확한 반복 또는 준-반복 유닛을 포함하고 이들은 고유 MaSp2 드래그라인 실크 단백질의 반복 유닛과 적어도 80%, 적어도 85%, 적어도 90%, 적어도 95%, 또는 적어도 99%의 아미노산 서열 동일성을 갖는다.
일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 하나 이상의 준-반복 유닛을 포함하고, 여기서, 각각의 준-반복 유닛의 아미노산 서열은 수학식 1에 의해 기재되고, 여기서, X1의 아미노산 서열 (“모티프”로 호칭됨)은 수학식 2에 의해 기재되어 있고 각각의 준-반복 유닛 내 무작위로 다양할 수 있다. 서열 [GPG-X1]n1 은 "제1 영역"으로서 언급되고 글라이신-풍부이다. 서열 (A)n2 는 "제2 영역"으로서 언급되고, 알라닌-풍부이다. 일부 실시 양태에서, n1의 값은 4, 5, 6, 7, 또는 8 중 임의의 하나이다. 일부 실시 양태에서, n2의 값은 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 또는 20 중 임의의 하나이다. 일부 실시 양태에서, n3의 값은 2 내지 20의 임의의 하나이다. 일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 수학식 1 및 2에 의해 기재된 준-반복 유닛과 적어도 80%, 90%, 95%, 또는 99%의 서열 동일성을 갖는 하나 이상의 준-반복 유닛을 포함한다.
{GGY - [GPG-X1]n1 - GPS-(A)n2 }n3 (수학식 1)
X1 = SGGQQ 또는 GAGQQ 또는 GQGPY 또는 AGQQ 또는 SQ (수학식 2)
일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 수학식 1 및 수학식 2에 의해 기재된 바와 같은 준-반복 유닛을 포함하고, 여기서, n1은 준-반복 유닛의 적어도 절반에 대해 4 또는 5이다. 일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 수학식 1 및 수학식 2에 의해 기재된 바와 같은 준-반복 유닛을 포함하고, 여기서, n2는 준-반복 유닛의 적어도 절반에 대해 5 또는 8이다.
본원에 사용된 바와 같은 용어 "짧은 준-반복 유닛"은 n1이 4 또는 5인 반복 유닛을 언급한다 (수학식 1에 나타낸 바와 같이). 본원에 사용된 바와 같은 용어 "긴 준-반복 유닛"은 n1이 6, 7 또는 8인 반복체를 언급한다 (수학식 1에 나타낸 바와 같이). 일부 실시 양태에서, n1은 준-반복 유닛의 적어도 절반에 대해 4 내지 5이다. 일부 실시 양태에서, n2는 준-반복 유닛의 적어도 절반에 대해 5 내지 8이다. 일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 3개의 “긴 준-반복 유닛”에 이어서 3개의 “짧은 준-반복 유닛”을 포함한다. 일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 단일 준-반복체에서 일렬로 2개 초과 또는 2회 초과의 동일한 X1 모티프를 갖지 않는 준-반복 유닛을 포함한다. 일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 동일한 위치에서 동일한 X1 모티프를 포함하는 준-반복 유닛을 포함한다. 일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 동일한 위치에서 동일한 수학식 2 서열을 포함하는 준-반복 유닛을 포함한다. 일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 준-반복 유닛을 포함하고, 여기서, 6개 중 3개 이하의 준-반복 유닛은 동일한 X1을 공유한다.
일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 Xqr 준-반복 유닛을 포함하고, 여기서
Xqr = Xsqr + Xlqr (수학식 3),
여기서, Xqr은 2 내지 20의 수이고; Xsqr은 짧은 준-반복체의 수 및 1 내지 (Xqr-1)의 수이고; Xlqr은 긴 준-반복체의 수 및 1 내지 (Xqr-1)의 수이다. 일부 실시 양태에서, Xqr은 2 내지 20의 수이다. 반복 유닛의 아미노산 서열의 비-제한적인 예는 표 3에 나타낸다.
표 3 - 실크 또는 실크 유사 단백질의 예시적 반복 유닛
일부 실시 양태에서, 실크 또는 실크 또는 실크 유사 단백질은 서열번호 17을 포함하는 하나 이상의 반복 유닛을 포함하고, 상기 반복 유닛은 6개 준-반복 유닛을 함유한다. 준-반복 유닛은 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 또는 20회 연결되어 약 50 kDal 내지 약 1,000 kDal의 폴리펩타이드 분자를 형성할 수 있다. 상기 반복 유닛은 또한 나노-결정성 영역과 관련된 폴리-알라닌 영역, 및 덜-결정성 영역을 함유하는 베타-턴과 관련된 글라이신 풍부 영역을 함유한다.
추가의 적합한 실크 또는 실크 또는 실크 유사 단백질의 비제한적인 예는 예를 들어 하기 문헌에 제공된다: 국제 특허 공개공보 WO/2016/201369, 2016년 12월 15일자로 공개됨; 미국 특허 출원 제62/394,683호, 2016년 9월 14일자로 출원됨; 미국 특허 출원 제15/705,185호, 2017년 9월 14일자로 출원됨, 미국 공개공보 제US20160222174호, 2016년 8월 4일자로 공개됨; 국제 특허 공개공보 WO2016/149414, 2016년 3월 16일자로 공개됨; 국제 특허 공개공보 WO 2014/066374, 2014년 1월 5일자로 공개됨, 및 국제 특허 공개공보 WO 2015/042164, 2015년 3월 26일자로 공개됨, 이의 각각은 이의 전문이 본원에 참조로 포함됨.
전형적으로, 분비 신호와 단백질의 작동 가능한 연결은 단백질을 암호화하는 폴리뉴클레오타이드 서열의 개시 코돈의 제거를 필요로 한다.
다른 성분
일부 실시 양태에서, 발현 작제물 내 포함되는 폴리뉴클레오타이드 서열은 단백질의 C-말단에 작동가능하게 연결된 태그 펩타이드 또는 폴리펩타이드를 추가로 암호화한다. 상기 태그 펩타이드 또는 폴리펩타이드는 재조합 단백질의 정제를 도와줄 수 있다. 태그 펩타이드 또는 폴리펩타이드의 비제한적인 예는 친화성 태그 (즉, 특정 제제 또는 매트릭스에 결합하는 펩타이드 또는 폴리펩타이드), 가용화 태그 (즉, 단백질의 적당한 폴딩을 도와주고 침전을 방지하는 펩타이드 또는 폴리펩타이드), 크로마토그래피 태그 (즉, 단백질의 크로마토그래피 성질을 변화시켜 특정 분리 기술에 걸쳐 상이한 해리를 부여하는 펩타이드 또는 폴리펩타이드), 에피토프 태그 (즉, 항체에 의해 결합되는 펩타이드 또는 폴리펩타이드), 형광성 태그, 크로마토그래피 태그, 효소 기질 태그 (즉, 특이적 효소 반응을 위한 기질인 펩타이드 또는 폴리펩타이드), 화학적 기질 태그 (즉, 특이적 말단 변형을 위한 기질인 펩타이드 또는 폴리펩타이드), 또는 이들의 조합체를 포함한다. 적합한 친화성 태그의 비제한적인 예는 말토스 결합 단백질 (MBP), 글루타티온-S-트랜스퍼라제 (GST), 폴리(His)태그, SBP-태그, 스트렙-태그, 및 칼모둘린-태그를 포함한다. 적합한 용해도 태그의 비제한적인 예는 티오레독신(TRX), 폴리(NANP), MBP, 및 GST를 포함한다. 크로마토그래피 태그의 비제한적인 예는 다중음이온성 아미노산 (예를 들어, FLAG-태그) 및 폴리글루타메이트 태그를 포함한다. 에피토프 태그의 비제한적인 예는 V5-태그, VSV-태그, Myc-태그, HA-태그, E-태그, NE-태그, Ha-태그, Myc-태그, 및 FLAG-태그를 포함한다. 형광성 태그의 비제한적인 예는 녹색 형광성 단백질 (GFP), 청색 형광성 단백질 (BFP), 시안 형광성 단백질 (CFP), 황색 형광성 단백질 (YFP), 오렌지 형광성 단백질 (OFP), 적색 형광성 단백질 (RFP), 및 이들의 유도체를 포함한다. 효소 기질 태그의 비제한적인 예는 비오티닐화 (예를 들어, AviTag, 비오틴 카복실 캐리어 단백질[BCCP])를 위해 적합한 서열 내 라이신을 포함하는 펩타이드 또는 폴리펩타이드를 포함한다. 화학적 기질 태그의 비제한적인 예는 FIAsH-EDT2와 반응을 위해 적합한 기질을 포함한다. C-말단 태그 펩타이드 또는 폴리펩타이드의 재조합 단백질로의 융합은 절단가능(예를 들어, TEV 프로테아제, 트롬빈, 인자 Xa, 또는 엔테로펩티다제)할 수 있거나 절단 가능하지 않을 수 있다.
일부 실시 양태에서, 발현 작제물 내 포함되는 폴리뉴클레오타이드 서열은 단백질과 재조합 분비 신호 간에 작동가능하게 연결된 링커 펩타이드를 추가로 암호화한다. 링커 펩타이드는 다양한 크기를 가질 수 있다. 일부 상기 실시 양태에서, 링커 펩타이드를 암호화하는 폴리뉴클레오타이드 서열은 제한 효소 부위를 포함하여 다른 폴리펩타이드 서열의 대체 또는 첨가를 가능하게 한다.
발현 작제물은 재조합 분비 신호에 작동가능하게 연결되는 단백질을 암호화하는 폴리뉴클레오타이드 서열에 작동가능하게 연결되는 프로모터를 추가로 포함하여 폴리뉴클레오타이드 서열의 전사를 구동시킬 수 있다. 프로모터는 항상성 프로모터 또는 유도성 프로모터일 수 있다. 유도는 예를 들어, 글루코스 억제, 갈락토스 유도, 슈크로스 유도, 포스페이트 억제, 티아민 억제 또는 메탄올 유도를 통해 일어난다. 적합한 프로모터는 본원에 제공된 재조합 숙주 세포 내 단백질의 발현을 매개하는 프로모터이다. 적합한 프로모터의 비제한적인 예는 피키아 파스토리스 ( Pichia pastoris ) 의 알콜 옥시다제 (AOX1) 프로모터 (pAOX1), 피키아 파스토리스의 글리세르알데하이드-3-포스페이트 데하이드로게나제 (GAP) 프로모터 (pGAP), YPT1 프로모터, 사카로마이세스 세레비지애 ( Saccharomyces cerevisae ) 의 3-포스포글리세레이트 키나제 1 (PGK1) 프로모터 (pPKG1), SSA4 프로모터, HSP82 프로모터, GPM1 프로모터, KAR2 프로모터, 피키아 파스토리스의 트리오스 포스페이트 이소머라제 1 (TPI1) 프로모터 (pTPI1), 피키아 파스토리스의 에놀라제 1 (ENO1) 프로모터 (pENO1), PET9 프로모터, PEX8 (PER3) 프로모터, AOX2 프로모터, AOD 프로모터, THI11 프로모터, DAS 프로모터, FLD1 프로모터, PHO89 프로모터, CUP1 프로모터, GTH1 프로모터, ICL1 프로모터, TEF1 프로모터, LAC4-PBI 프로모터, T7 프로모터, TAC 프로모터, GCW14 프로모터, GAL1 프로모터, λPL 프로모터, λPR 프로모터, 베타-락타마제 프로모터, spa 프로모터, CYC1 프로모터, TDH3 프로모터, GPD 프로모터, 사카로마이세스 세레비지애의 해독 개시 인자 1 (TEF1) 프로모터, ENO2 프로모터, PGL1 프로모터, GAP 프로모터, SUC2 프로모터, ADH1 프로모터, ADH2 프로모터, HXT7 프로모터, PHO5 프로모터 및 CLB1 프로모터를 포함한다. 사용될 수 있는 추가의 프로모터는 당업계에 공지되어 있다.
발현 작제물은 재조합 분비 신호에 작동가능하게 연결된 단백질을 암호화하는 폴리뉴클레오타이드 서열에 작동가능하게 연결된 프로모터를 추가로 포함하여 폴리뉴클레오타이드 서열의 전사를 구동할 수 있다. 적합한 종결자는 본원에 제공된 재조합 숙주 세포 내 전사를 종결시키는 종결자다. 적합한 종결자의 비제한적인 예는 피키아 파스토리스의 AOX1 종결자 (tAOX1), PGK1 종결자, 및 TPS1 종결자를 포함한다. 추가의 종결자는 당업계에 공지되어 있다.
재조합 벡터
본원에 제공된 재조합 벡터는 본원에 제공된 발현 작제물을 포함한다. 일부 실시 양태에서, 재조합 벡터는 다중 발현 작제물 (예를 들어, 2, 3, 4, 5, 등)을 포함한다. 일부 이러한 실시 양태에서, 발현 작제물은 동일한다. 다른 이러한 실시 양태에서, 적어도 2개의 발현 작제물은 동일하지 않다. 적어도 2개의 발현 작제물이 동일하지 않은 실시 양태에서, 적어도 2개의 발현 작제물은 단백질, 재조합 분비 신호, 프로모터, 종결자 및/또는 이들을 암호화하는 다른 성분에서 서로 상이할 수 있다.
재조합 벡터는 재조합 숙주 세포에서 재조합 벡터의 전파에 적합한 요소를 추가로 포함할 수 있다. 이러한 다른 요소의 비제한적인 예는 복제 기원 및 선택 마커 (예를 들어, 항생제 내성 유전자, 독립영양성 마커)를 포함한다. 복제 기원 및 선택 마커는 당업계에 공지되어 있다. 다양한 실시 양태에서, 복제 기원은 박테리아 또는 효모 복제 기원이다. 일부 구체예에서, 복제 기원은 피치아 자율 복제 서열(Pichia autonomously replicating sequences, PARS)이다. 일부 실시 양태에서, 선택 마커는 약물 내성 마커이다. 약물 내성 마커는 세포가 또한 세포를 사멸시키는 외인성으로 부가된 약물의 독성을 제거하도록 할 수 있다. 약물 내성 마커의 도해적 예는 암피실린, 테트라사이클린, 카나마이신, 블레오마이신, 스트렙토마이신, 하이그로마이신, 네오마이신, Zeocin™ 등과 같은 항생제에 대한 내성에 대한 것들을 포함하지만 이에 제한되지 않는다. 다른 실시 양태에서, 선택 마커는 독립영양성 마커이다. 독립영양성 마커는 세포가 필수 성분이 없는 배지에서 성장되도록 하면서 필수 성분 (일반적으로 아미노산)을 합성할 수 있게 한다. 적합한 독립영양성 마커는 예를 들어, hisD를 포함하고 이는 히스티디놀의 존재하에 히스티딘 부재 배지 내 성장을 가능하게 한다. 다른 선택 마커는 블레오마이신-내성 유전자, 메탈로티오네인 유전자, 하이그로마이신 B-포스포트랜스퍼라제 유전자, AURI 유전자, 아데노신 데아미나제 유전자, 아미노글리코사이드 포스포트랜스퍼라제 유전자, 디하이드로폴레이트 리덕타제 유전자, 티미딘 키나제 유전자, 및 크산틴-구아닌 포스포리보실트랜스퍼라제 유전자를 포함한다.
재조합 벡터는 발현 작제물의 숙주 세포의 게놈에서 특정 위치로의 통합을 지시할 수 있는 표적화 서열을 추가로 포함할 수 있다. 이러한 표적화 서열의 비제한적인 예는 숙주 세포의 게놈에 포함된 폴리뉴클레오타이드 서열과 상동성인 폴리뉴클레오타이드 서열이다. 일부 실시 양태에서, 표적화 서열은 숙주 세포의 게놈에서 반복적인 요소와 상동성이다. 일부 실시 양태에서, 표적화 서열은 숙주 세포에서 이식가능한 요소에 상동성이다.
재조합 숙주 세포
본원에 제공된 재조합 숙주 세포는 본원에 제공된 발현 작제물을 포함하는 세포이다. 재조합 숙주 세포는 포유동물, 식물, 조류, 진균류 또는 미생물 기원일 수 있다.
적합한 진균류의 비제한적인 예는 메탄올자화 효모, 필라멘트성 효모, 아륵술라 아데니니보란스 ( Arxula adeninivorans ), 아스퍼길러스 나이거 ( Aspergillus niger), 아스퍼질러스 나이거 변이체 ( Aspergillus niger var). 아와모리 ( awamori ), 아스퍼질러스 오리재 ( Aspergillus oryzae ), 캔디다 에첼시 ( Candida etchellsii ), 캔디다 구일리에르몬디 ( Candida guilliermondii ), 캔디다 후밀리스 ( Candida humilis), 캔디다 리롤리티카 ( Candida lipolytica ), 캔디다 슈도트로피칼리스 (Candida pseudotropicalis ), 캔디다 우틸리스 ( Candida utilis ), 캔디다 베르사틸리스 ( Candida versatilis ), 데바리오마이세스 한세닐 ( Debaryomyces hansenii ), 엔도티아 파라시티카 ( Endothia parasitica ), 에레모테시움 아스흐비이 (Eremothecium ashbyii ), 푸사리움 모닐리포르메 ( Fusarium moniliforme ), 한세눌라 폴리모르파 ( Hansenula polymorpha ), 클루이베로마이세스 락티스 (Kluyveromyces lactis ), 클루베로마이세스 마륵시아누스 ( Kluyveromyces marxianus), 클루베로마이세스 써모톨레란스 ( Kluyveromyces thermotolerans ), 모르테이렐라 비나세아 변이체 ( Morteirella vinaceae var). 라피노세우틸리저 (raffinoseutilizer), 무코르 미에헤이 ( Mucor miehei ), 무코르 미에헤이 변이체 (Mucor miehei var)를 포함하고, 쿠니 엣 에머슨 ( Cooney et Emerson), 무코르 푸 실루스 린드트 ( Mucor pusillus Lindt ), 페니실리움 로쿠에포르티 ( Penicillium roquefortii), 피키아 메타놀리카 ( Pichia methanolica ), 피키아 ( Pichia ) ( 코마가타엘라 ( Komagataella )) 파스토리스 ( pastoris ), 피키아 ( Pichia ) ( 세페로마이세스 (Scheffersomyces)) 스티피티스 ( stipitis ), 리조푸스 니베우스 ( Rhizopus niveus), 로도토룰라 종( Rhodotorula sp .), 사카로마이세스 바야누스 (Saccharomyces bayanus ), 사카로마이세스 베티쿠스 ( Saccharomyces beticus ), 사카로마이세스 세레비지애 ( Saccharomyces cerevisiae ), 사카로마이세스 체발리에리 (Saccharomyces chevalieri ), 사카로마이세스 디아스타티쿠스 ( Saccharomyces diastaticus), 사카로마이세스 엘립소이데우스 ( Saccharomyces ellipsoideus ), 사카로마이세스 엑시구스 ( Saccharomyces exiguus ), 사카로마이세스 플로렌티누스 (Saccharomyces florentinus ), 사카로마이세스 프라길리스 ( Saccharomyces fragilis), 사카로마이세스 파스토리아누스 ( Saccharomyces pastorianus ), 사카로마이세스 폼베 ( Saccharomyces pombe ), 사카로마이세스 사케 ( Saccharomyces sake), 사카로마이세스 우바룸 ( Saccharomyces uvarum ), 스포리디오볼루스 요흔소니 ( Sporidiobolus johnsonii ), 스포리디오볼루스 살모니컬러 ( Sporidiobolus salmonicolor), 스로로볼로마이세스 로세우스 ( Sporobolomyces roseus ), 트리코더마 레시 ( Trichoderma reesi ), 크산토필로마이세스 덴드로로우스 (Xanthophyllomyces dendrorhous ), 야로위아 리폴리티카 ( Yarrowia lipolytica ), 자이고사카로마이세스 로욱시 ( Zygosaccharomyces rouxii ), 및 이들의 유도체 및 교배체를 포함한다.
적합한 미생물의 비제한적인 예는 아세토박터 수복시단스 ( Acetobacter suboxydans), 아세토박터 크실리눔 ( Acetobacter xylinum ), 액티노플레인 미소우리엔시스 ( Actinoplane missouriensis ), 아트로스피라 플라텐시스 ( Arthrospira platensis), 아르트로스피라 맥시마 ( Arthrospira maxima), 바실러스 세레우스 (Bacillus cereus ), 바실러스 코아굴란스 (Bacillus coagulans ), 바실러스 리케니포르미스 (Bacillus licheniformis ), 바실러스 스테아로테르모필루스 (Bacillus stearothermophilus), 바실러스 서브틸리스 (Bacillus subtilis ), 에스케리치아 콜리 ( Escherichia coli ), 락토바실러스 액시도필루스 (Lactobacillus acidophilus), 락토바실러스 불가리쿠스 (Lactobacillus bulgaricus ), 락토바실러스 류테리 (Lactobacillus reuteri ), 락토코쿠스 락티스 ( Lactococcus lactis ), 락토코쿠스 락티스 란세필드 그룹 N ( Lactococcus lactis Lancefield Group N), 류코노스톡 시 트로보룸 ( Leuconostoc citrovorum ), 류코노스톡 덱스트라니쿰 ( Leuconostoc dextranicum), 류코노스톡 메센테로이데스 균주 ( Leuconostoc mesenteroides strain) NRRL B-512(F), 마이크로코쿠스 리소데이크티쿠스 ( Micrococcus lysodeikticus), 스피룰리나 ( Spirulina ), 스트렙토코쿠스 크레모리스 (Streptococcus cremoris ), 스트렙토코쿠스 락티스 (Streptococcus lactis ), 스트렙토코쿠스 락티스 서브종 디아세틸락티스 (Streptococcus lactis subspecies diacetylactis), 스트렙토코쿠스 써모필러스 (Streptococcus thermophilus ), 스트렙토마이세스 차타노겐시스 ( Streptomyces chattanoogensis ), 스트렙토마이세스 그 리세우스 ( Streptomyces griseus), 스트렙토마이세스 나탈렌시스 ( Streptomyces natalensis), 스트렙토마이세스 올리바세우스 ( Streptomyces olivaceus ), 스트렙토마이세스 올리보크로모게네스 ( Streptomyces olivochromogenes ), 스트렙토마이세스 루비기노수스 (Streptomyces rubiginosus ), 크산토모나스 캄페스트리스 ( Xanthomonas campestris), 및 이들의 유도체 및 교배체를 포함한다.
재조합 숙주 세포로서 사용될 수 있는 추가의 균주는 당업계에 공지되어 있다. 상기 용어 "재조합 숙주 세포"는 특정 대상체 세포뿐만 아니라 상기 세포의 후손을 언급하는 것으로 의도되는 것으로 이해되어야만 한다. 특정 변형이 돌연변이 또는 환경적 영향으로 인해 후속 세대에서 일어날 수 있으므로 상기 후손은 사실 모 세포와 동일하지 않을 수 있지만 본원에 사용된 바와 같은 용어 "재조합 숙주 세포"의 범위 내에 여전히 포함된다.
일부 실시 양태에서, 발현 작제물은 재조합 숙주 세포의 게놈(예를 들어, 염색체) 내에, 예를 들어 상동 재조합 또는 표적화된 통합을 통해 안정적으로 통합된다. 게놈 통합을 위한 적합한 부위의 비제한적인 예는 사카로마이세스 세레비지애 게놈의 Ty1 유전자좌, 피키아 파스토리스 게놈의 rDNA 및 HSP82 유전자좌, 및 재조합 숙주 세포의 게놈 전체에 흩어진 카피를 갖는 이식가능한 요소를 포함한다. 다른 실시 양태에서, 발현 작제물은 재조합 숙주 세포의 게놈 내에 안정적으로 통합되지 않고 오히려 염색체 외적으로(예를 들어, 플라스미드에서) 유지된다.
재조합 단백질의 생산은 재조합 숙주 세포에 포함된 본원에서 제공된 발현 작제물의 카피 수 및 발현 작제물에 포함된 폴리뉴클레오타이드 서열의 전사 속도에 의해 영향을 받을 수 있다. 일부 실시 양태에서, 재조합 숙주 세포는 단일 발현 작제물을 포함한다. 다른 구체예에서, 재조합 숙주 세포는 2개 이상(예를 들어, 3, 4, 5, 또는 그 이상)의 발현 작제물을 포함한다. 일부 실시 양태에서, 재조합 숙주 세포는 강한 프로모터에 작동가능하게 연결된 폴리뉴클레오타이드 서열을 포함하는 발현 작제물을 포함한다. 강한 프로모터의 비제한적인 예는 피키아 파스토리스의 pGCW14 프로모터를 포함한다. 일부 실시 양태에서, 재조합 숙주 세포는 배지 프로모터에 작동하는 연결된 폴리뉴클레오타이드 서열을 포함하는 발현 작제물을 포함한다. 이러한 배지 프로모터의 비제한적인 예는 피키아 파스토리스의 pGAP 프로모터를 포함한다. 일부 실시 양태에서, 재조합 숙주 세포는 약한 프로모터에 작동가능하게 연결된 폴리뉴클레오타이드 서열을 포함하는 발현 작제물을 포함한다.
본원에서 제공된 재조합 분비 신호는 재조합 단백질의 높은 분비 수율을 제공한다. 따라서, 다양한 실시 양태에서, 재조합 숙주 세포는 단백질의 총 수율의 중량으로 적어도 1%, 5%, 10%, 20%, 또는 30%; 1% 내지 100%, 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, 또는 10%; 10% 내지 100%, 90%, 80%, 70%, 60%, 50%, 40%, 30%, 또는 20%; 20% 내지 100%, 90%, 80%, 70%, 60%, 50%, 40%, 또는 30%; 30% 내지 100%, 90%, 80%, 70%, 60%, 50%, 또는 40%; 40% 내지 100%, 90%, 80%, 70%, 60%, 또는 50%; 50% 내지 100%, 90%, 80%, 70%, 또는 60%; 60% 내지 100%, 90%, 80%, 또는 70%; 70% 내지 100%, 90%, 또는 80%; 80% 내지 100%, 또는 90%; 또는 90% 내지 100%의 발현 작제물 내 포함된 폴리뉴클레오타이드 서열에 의해 암호화되는 단백질의 분비 수율을 생산한다. 생산된 재조합 단백질의 동일성은 HPLC 정량, 웨스턴 블롯 분석, 폴리아크릴아미드 겔 전기영동, 및 2-차원 질량 분광측정기 (2D-MS/MS) 서열 동정에 의해 확인될 수 있다.
발효물
본원에 제공된 발효물은 본원에 제공된 재조합 숙주 세포 및 재조합 숙주 세포를 성장시키기 위해 적합한 배양 배지를 포함한다.
발효물은 재조합 숙주 세포를, 세포 생존 및/또는 성장을 위해 재조합 숙주 세포에 의해 요구되는 영양물을 제공하는 배양 배지 중에서 배양함에 의해 수득된다. 상기 배양 배지는 전형적으로 과량의 탄소원을 함유한다. 적합한 탄소원의 비제한적인 예는 모노사카라이드, 디사카라이드, 폴리사카라이드, 알콜 및 이들의 조합물을 포함한다. 적합한 모노사카라이드의 비제한적인 예는 글루코스, 갈락토스, 만노스, 프럭토스, 리보스, 크실로스, 아라비노스, 리보스 및 이들의 조합물을 포함한다. 적합한 디사카라이드의 비제한적인 예는 슈크로스, 락토스, 말토스, 테할로스, 셀로비오스 및 이들의 조합물을 포함한다. 적합한 폴리사카라이드의 비제한적인 예는 라피노스, 전분, 글리코겐, 글리칸, 셀룰로스, 키틴, 및 이들의 조합물을 포함한다. 적합한 알콜의 비제한적인 예는 메탄올 및 글리콜을 포함한다.
본원에서 제공된 재조합 분비 신호는 재조합 단백질의 고분비 수율을 제공한다. 따라서, 다양한 실시 양태에서, 본원에 제공된 발효물은 분비된 재조합 단백질로서 재조합 단백질의 총 수율의 적어도 1중량%, 5중량%, 10중량%, 20중량%, 또는 30중량%; 1중량% 내지 100중량%, 90중량%, 80중량%, 70중량%, 60중량%, 50중량%, 40중량%, 30중량%, 20중량%, 또는 10중량%; 10중량% 내지 100중량%, 90중량%, 80중량%, 70중량%, 60중량%, 50중량%, 40중량%, 30중량%, 또는 20중량%; 20중량% 내지 100중량%, 90중량%, 80중량%, 70중량%, 60중량%, 50중량%, 40중량%, 또는 30중량%; 30중량% 내지 100중량%, 90중량%, 80중량%, 70중량%, 60중량%, 50중량%, 또는 40중량%; 40중량% 내지 100중량%, 90중량%, 80중량%, 70중량%, 60중량%, 또는 50중량%; 50중량% 내지 100중량%, 90중량%, 80중량%, 70중량%, 또는 60중량%; 60중량% 내지 100중량%, 90중량%, 80중량%, 또는 70중량%; 70중량% 내지 100중량%, 90중량%, 또는 80중량%; 80중량% 내지 100중량%, 또는 90중량%; 또는 90중량% 내지 100중량%를 포함한다. 일부 실시 양태에서, 발효물의 배양 배지는 재조합 숙주 세포에 의해 생성되는 재조합 단백질을 적어도 0.1 g/L, 적어도 0.5 g/L, 적어도 1 g/L, 적어도 2 g/L, 적어도 5 g/L, 적어도 7 g/L, 적어도 10 g/L, 적어도 15 g/L, 또는 적어도 20 g/L; 0.1 g/L 내지 30 g/L, 내지 25 g/L, 내지 20 g/L, 내지 15 g/L, 내지 10 g/L, 내지 7 g/L, 내지 5 g/L, 내지 2 g/L, 내지 1 g/L, 또는 내지 0.5 g/L; 0.5 g/L 내지 30 g/L, 내지 25 g/L, 내지 20 g/L, 내지 15 g/L, 내지 10 g/L, 내지 7 g/L, 내지 5 g/L, 내지 2 g/L, 또는 내지 1 g/L; 1 g/L 내지 30 g/L, 내지 25 g/L, 내지 20 g/L, 내지 15 g/L, 내지 10 g/L, 내지 7 g/L, 내지 5 g/L, 또는 내지 2 g/L; 2 g/L 내지 30 g/L, 내지 25 g/L, 내지 20 g/L, 내지 15 g/L, 내지 10 g/L, 내지 7 g/L, 또는 내지 5 g/L; 5 g/L 내지 30 g/L, 내지 25 g/L, 내지 20 g/L, 내지 15 g/L, 내지 10 g/L, 또는 내지 7 g/L; 7 g/L 내지 30 g/L, 내지 25 g/L, 내지 20 g/L, 내지 15 g/L, 또는 내지 10 g/L; 10 g/L 내지 30 g/L, 내지 25 g/L, 내지 20 g/L, 또는 내지 15 g/L; 15 g/L 내지 30 g/L, 내지 25 g/L, 또는 내지 20 g/L; 20 g/L 내지 30 g/L, 또는 내지 25 g/L; 또는 25 g/L 내지 30 g/L 포함한다.
재조합 단백질을
고분비
수율로 생산하기 위한 방법
본원에 제공된 것은 재조합 단백질을 고분비 수율로 생산하기 위한 방법이다. 상기 방법은 일반적으로 당업계에 널리 공지되어 있고 달리 지적되지 않는 경우 본원 명세서 전반에 걸쳐 인용되고 논의된 다양한 일반 및 보다 구체적인 참조문헌에 기재된 바와 같이 통상적인 방법에 따라 수행된다. 문헌참조: 예를 들어, Sambrook et al. Molecular Cloning:A Laboratory Manual, 2d ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989; Ausubel et al. Current Protocols in Molecular Biology, Greene Publishing Associates, 1992, and Supplements to 2002); Harlow and Lane, Antibodies:A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1990; Taylor and Drickamer, Introduction to Glycobiology, Oxford Univ.Press, 2003; Worthington Enzyme Manual, Worthington Biochemical Corp., Freehold, N.J.;Handbook of Biochemistry:Section A Proteins, Vol I, CRC Press, 1976; Handbook of Biochemistry:Section A Proteins, Vol II, CRC Press, 1976; Essentials of Glycobiology, Cold Spring Harbor Laboratory Press, 1999.
본원에 제공된 방법은 본원에 제공된 재조합 숙주 세포를 본원에 제공된 발효물을 수득하기 위해 적합한 조건 하에서 배양 배지 내 본원에 제공된 재조합 숙주 세포를 배양하는 단계 (도 1에서 단계 1003)를 포함한다. 이들 방법에 사용하기 위해 적합한 배양 배지는 적합한 배양 조건으로서 당업계에 공지되어 있다. 예를 들어, 효모 숙주 세포를 배양하기 위한 세부 사항은 당업계에 기재되어 있다: Idiris et al. (2010) Appl.Microbiol.Biotechnol.86 :403-417 ; Zhang et al. (2000) Biotechnol.Bioprocess.Eng. 5:275-287; Zhu (2012) Biotechnol.Adv.30 :1158-1170 ; 및 Li et al. (2010) MAbs 2:466-477.
일부 실시 양태에서, 상기 방법은 본원에서 제공된 발현 작제물 및/또는 재조합 벡터를 작제하는 단계(도 1에서 단계 1001)를 추가로 포함한다. 발현 작제물 및 재조합 벡터를 작제하기 위한 방법은 당업계에 공지되어 있다. 일부 실시 양태에서, 발현 작제물 및/또는 재조합 벡터는 합성적으로 생성된다. 다른 구현에에서, 발현 작제물 및/또는 재조합 벡터는 유기체, 세포, 조직 또는 플라스미드 작제물로부터 표준 과정에 의해 단리되거나 PCR 증폭된다. 일부 실시 양태에서, 발현 작제물 및/또는 재조합 벡터는 특정 숙주 세포에서 발현을 위해 코돈 최적화한다.
일부 실시 양태에서, 상기 방법은 재조합 단백질의 발현 (예를 들어, 폴리뉴클레오타이드 수 및/또는 및/또는 폴리뉴클레오타이드 서열에 작동가능하게 연결된 프로모터의 강도를 증가시키거나 감소시킴에 의해) 및 재조합 단백질의 분비 효율 (예를 들어, 특정 재조합 분비 신호를 선택함에 의해)의 균형을 유지시키는 단계를 포함한다.
일부 실시 양태에서, 상기 방법은 세포를 본원에서 제공된 발현 작제물 또는 재조합 벡터로 형질전환시켜 본원에 제공된 재조합 숙주 세포를 수득하는 단계 (도 1에서 단계 1002)를 추가로 포함한다. 상기 형질전환을 위해, 재조합 벡터는 환형이거나 선형일 수 있다. 세포를 형질전환시키기 위한 방법은 당업계에 널리 공지되어 있다. 상기 방법의 비제한적인 예는 인산칼슘 형질감염, 덴드리머 형질감염, 리포좀 형질감염 (예를 들어, 양이온성 리포좀 형질감염), 양이온성 중합체 형질감염, 전기천공, 세포 압착 (squeezing), 소노포레이션 (sonoporation), 광학 형질감염, 원형질체 융합, 임팔레펙션 (impalefection), 유체역학적 전달, 유전자 검, 마그네토펙션 (magnetofection), 스페로플라스트 (spheroblast) 생성, 폴리에틸렌 글리콜 (PEP) 처리 및 바이러스 형질도입을 포함한다. 당업자는 특정 유형의 세포에 대해 보다 양호한 연구 벡터를 도입하기 위한 특정 기술에 대한 당업자의 지식을 기준으로 본원에 기재된 발현 작제물 또는 재조합 벡터로 세포를 형질전환시키기 위해 적합한 하나 이상의 방법을 선택할 수 있다. 본원에 제공된 발현 작제물 또는 재조합 벡터를 포함하는 재조합 세포 형질전환체는 예를 들어, 세포의 성장을 위해 또는 이를 저해하기 위한 선택을 허용하는 재조합 벡터에 의해 암호화된 약물 내성 또는 독립영양 마커를 발현시킴에 의해 또는 다른 수단 (예를 들어, 발현 작제물 또는 재조합 벡터 내 포함되는 광 방출 펩타이드의 검출, 개별 재조합 숙주 세포 콜로니의 분자 분석 [예를 들어, 제한 효소 맵핑, PCR 증폭 또는 단리된 염색체외 벡터 또는 염색체 통합 부위에 의해])에 의해 용이하게 동정될 수 있다.
일부 실시 양태에서, 상기 방법은 본원에 제공된 발효로부터 분비된 재조합 단백질을 추출하는 단계 (도 1에서 단계 1004)를 추가로 포함한다. 추출은 분비된 단백질을 정제하기 위한 당업계에 공지된 다양한 방법에 의해 일어날 수 있다. 상기 방법에서 공통된 단계는 세포의 펠렛화, 및 재조합 숙주 세포 및 세포 잔해물을 포함하는 세포 펠렛의 제거를 유발하는 속도로의 원심분리에 이어서 침전제 (예를 들어, 5 내지 60% 포화의 황산암모늄에 이어서 원심분리) 또는 친화성 분리 (예를 들어, 재조합 단백질 또는 이들의 C-말단 태그 [예를 들어, FLAG, 헤마글루티닌]에 특이적으로 결합하는 항체와의 면역학적 상호작용, 또는 6 내지 8개 히스티딘 잔기들로 태그된 폴리펩타이드의 단리를 위해 니켈 컬럼에 결합시킴을 통해)를 사용한 재조합 단백질의 침전을 포함한다. 현탁된 재조합 단백질은 투석하여 용해된 염을 제거할 수 있다. 추가로, 투석된 재조합 단백질은 가열하여 다른 단백질을 변성시키고 변성된 단백질은 원심분리에 의해 제거할 수 있다.
실시예
실시예
1:
실크
유사 단백질을 고 분비 수율로 생산하는
피키아
파스토리스
재조합 숙주 세포의 생성
실크 유사 단백질을 분비하는 피키아 파스토리스 ( 코마가타엘라 파피 (Komagataella phaffii )) 재조합 숙주 세포는 GS115 (NRRL Y15851)의 HIS+ 유도체를 다양한 재조합 벡터로 형질전환시킴에 의해 생성하였다.
재조합 벡터 (도 2 참조)는 다양한 N-단말 재조합 분비 신호에 작동가능하게 연결된 실크 유사 단백질(서열번호 114)을 암호화하는 폴리뉴클레오타이드 서열을 포함하는 발현 작제물을 포함한다. 재조합 분비 신호는 *프로-αMF(sc) (서열번호 2) 또는 프로-EPX1(pp) (서열번호 144)에 작동가능하게 연결된 N-말단 신호 펩타이드로 이루어진다. 실크 유사 단백질은 C-말단 FLAG-태그에 작동적으로 추가로 연결되었다. 폴리뉴클레오타이드 서열 각각은 프로모터 (pGCW14) 및 종결자 (tAOX1 pA 신호)에 의해 플랭킹되었다. 재조합 벡터는 피키아 파스토리스 게놈 내에서 ICL1, HSP82, 또는 THI13 유전자좌의 바로 3' 영역에 바라현 작제물의 통합을 지시하는 표적화 영역, 세균 및 효모 형질전환체, 및 세균의 복제 기원의 선택에 대한 우성 내성 마커를 추가로 포함한다.
재조합 벡터를 전기천공을 통해 피키아 파스토리스 숙주 세포로 형질전환시켜 재조합 숙주 균주를 생성시켰다. 형질전환체는 항생제가 보충된 YPD 한천 플레이트 상에 분주하였고 30℃에서 48시간 동안 항온처리하였다.
각각의 최종 형질전환으로부터의 클론을 96-웰 블록에서 400 μL의 완충 글리세롤-복합체 배지 (BMGY)에 접종하고, 1,000 rpm에서 진탕과 함께 30℃에서 48시간 동안 항온처리하였다. 48시간 항온처리 후, 4 μL의 각각의 배양물을 사용하여 96-웰 블록에서 400 μL의 최소 배지에 접종하고 이어서 30℃에서 48시간 동안 항온처리하였다.
구아니딘 티오시아네이트를 세포 배양물에 2.5 M의 최종 농도로 첨가하여 ELISA에 의한 측정을 위해 재조합 단백질을 추출하였다. 5분 항온처리 후, 용액을 원심분리하고 상등액을 샘플 채취하였다.
도 3에 나타낸 바와 같이, 다수의 재조합 분비 신호는 프리-OST1(sc) / *프로-αMF(sc) 재조합 분비 신호 및/또는 프리-αMF(sc) / *프로-αMF(sc) 분비 신호 보다 더 높은 분비 수율의 실크 유사 단백질을 생산하는 반면, 다른 것은 더 낮은 분비 수율로 생산하였다.
도 4에 나타낸 바와 같이, 재조합 분비 신호가 프로-EPX1(pp) 보다는 프로-αMF(sc)를 포함할 때, 실크 유사 단백질의 분비 수율이 상당히 높았다. 도 4에 추가로 나타낸 바와 같이, 재조합 분비 신호 프리-EPX1(pp) / *프로-αMF(sc) 보다는 재조합 분비 신호 프리-GCW14(pp) / *프로-αMF(sc)에 의해 약간 더 높은 분비 수율을 얻었다.
도 5 및 도 6은 실크 유사 단백질의 분비 수율을 달성하는 본원에 제공된 추가의 재조합 분비 신호를 보여준다.
실시예
2: 알파-아밀라제 또는 녹색 형광성
단백질을 높은
분비율로 생산하는 피키아 파스토리스 재조합 숙주 세포의 생성
알파 아밀라제 또는 녹색 형광성 단백질을 분비하는 피키아 파스토리스 ( 코마가타엘라 파피 ( Komagataella phaffii )) 재조합 숙주 세포는 GS115 (NRRL Y15851)의 HIS+ 유도체를 다양한 재조합 벡터로 형질전환시킴에 의해 생성하였다.
재조합 벡터 (도 7 참조)는 하기를 암호화하는 폴리뉴클레오타이드 서열을 포함하는 발현 작제물을 포함하였고, 알파-아밀라제 (서열번호 145) 또는 녹색 형광성 단백질 (서열번호 146) 이들은 다양한 N-말단 재조합 분비 시그날에 작동가능하게 연결되어 있다. 재조합 분비 신호는 *프로-αMF(sc) (서열번호 2)에 작동가능하게 연결된 N-말단 신호 펩타이드로 이루어져 있다. 알파-아밀라제 또는 녹색 형광성 단백질은 추가로 C-말단 FLAG-태그에 작동가능하게 연결되어 있다. 폴리뉴클레오타이드 서열 각각은 프로모터 (pGCW14) 및 종결자 (tAOX1 pA 신호)에 의해 플랭킹되어 있다. 재조합 벡터는 추가로 피키아 파스토리스 게놈 내에 THI4 유전자좌의 바로 3'의 영역으로 발현 작제물의 통합을 지시하는 표적화 영역, 세균 및 효모 형질전환체의 선별을 위한 우성 내성 마커, 및 세균 복제 오리진을 포함하였다.
재조합 벡터로 피키아 파스토리스 숙주 세포를, 전기천공을 통해 형질전환시켜 재조합 숙주 균주를 생성하였다. 형질전환체는 항생제가 보충된 YPD 한천 플레이트 상에 분주하였고 30℃에서 48 내지 96시간 동안 항온처리하였다.
각각의 최종 형질전환으로부터의 클론은 96웰 블록에서 400 μL의 완충 글리세롤-복합체 배지(BMGY)에 접종하고, 1,000 rpm에서 진탕과 함께 30℃에서 48시간 동안 항온처리하였다. 48시간 항온처리 후, 4 μL의 각각의 배양물을 사용하여 96-웰 블록에서 400 μL의 최소 배지에 접종하고 이어서 30℃에서 48시간 동안 항온처리하였다.
구아니딘 티오시아네이트를 세포 배양물에 2.5 M의 최종 농도로 첨가하여 ELISA에 의한 측정을 위해 재조합 단백질을 추출하였다. 5분의 항온처리 후, 용액을 원심분리하고 상등액을 샘플링하였다.
도 8에 나타낸 바와 같이, 프리-EPX1(pp)/*프로-αMF(sc) 및 프리-PEP4(sc)/*프로-αMF(sc) 재조합 분비 신호는 프리- αMF(sc)/*프로-αMF(sc) 재조합 분비 신호보다 높은 분비 수율로 아밀라제를 생성하였고 프리-DSE4(pp)/*프로-αMF(sc) 분비 신호는 대략적으로 동일한 양의 분비된 아밀라제를 생성하였다.
도 9에 나타낸 바와 같이, 프리-EPX1(pp)/*프로-αMF(sc) 재조합 분비 신호는 프리- αMF(sc)/*프로-αMF(sc) 재조합 분비 신호 보다 높은 분비 수율로 녹색 형광성 단백질을 생성하였고, 프리-PEP4(sc)/*프로-αMF(sc) 및 프리-DSE4(pp)/*프로-αMF(sc) 분비 신호는 덜 분비된 형광성 단백질을 생성하였다.
본원의 개시내용에 대한 이전의 기재는 설명을 목적으로 제공되었고; 본 발명의 범위에 국한되거나 제한되는 것으로 의도되지 않는다.
상기 실시예에서 사용되는 수 (예를 들어, 양, 온도 등)와 관련된 정확도를 보장하기 위한 노력이 수행되었지만, 일부 실험 오류 및 편차는 물론 허용되어야만 한다. 실시예에 사용된 시약은 일반적으로 시판되고 있거나 시판되는 기구, 당업계에 공지된 방법 또는 시약을 사용하여 제조될 수 있다. 상기 실시예는 본 발명의 많은 상이한 구현예에 대한 구체적인 기재를 제공하는 것으로 의도되지 않는다. 당업자는 많은 변화 및 변형이 첨부된 청구항의 취지 또는 범위로부터 벗어나는 것 없이 실시예에 제공된 구현예에 만들어질 수 있음을 인지할 것이다.
표 4 - 추가 서열
<110> BOLT THREADS, INC.
<120> COMPOSITIONS AND METHODS FOR PRODUCING HIGH SECRETED YIELDS OF
RECOMBINANT PROTEINS
<130> 27576-39722/WO
<140> PCT/US2018/021812
<141> 2018-03-09
<150> 62/470,144
<151> 2017-03-10
<160> 154
<170> PatentIn version 3.5
<210> 1
<211> 70
<212> PRT
<213> Saccharomyces cerevisiae
<400> 1
Ala Pro Val Asn Thr Thr Thr Glu Asp Glu Thr Ala Gln Ile Pro Ala
1 5 10 15
Glu Ala Val Ile Gly Tyr Leu Asp Leu Glu Gly Asp Phe Asp Val Ala
20 25 30
Val Leu Pro Phe Ser Asn Ser Thr Asn Asn Gly Leu Leu Phe Ile Asn
35 40 45
Thr Thr Ile Ala Ser Ile Ala Ala Lys Glu Glu Gly Val Ser Leu Asp
50 55 60
Lys Arg Glu Ala Glu Ala
65 70
<210> 2
<211> 70
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 2
Ala Pro Val Asn Thr Thr Thr Glu Asp Glu Thr Ala Gln Ile Pro Ala
1 5 10 15
Glu Ala Val Ile Gly Tyr Ser Asp Leu Glu Gly Asp Phe Asp Val Ala
20 25 30
Val Leu Pro Phe Ser Asn Ser Thr Asn Asn Gly Leu Leu Phe Ile Asn
35 40 45
Thr Thr Ile Ala Ser Ile Ala Ala Lys Glu Glu Gly Val Ser Leu Glu
50 55 60
Lys Arg Glu Ala Glu Ala
65 70
<210> 3
<211> 27
<212> PRT
<213> Bos taurus
<400> 3
Met Asp Ser Lys Gly Ser Ser Gln Lys Gly Ser Arg Leu Leu Leu Leu
1 5 10 15
Leu Val Val Ser Asn Leu Leu Leu Cys Ser Ala
20 25
<210> 4
<211> 18
<212> PRT
<213> Gallus gallus
<400> 4
Met Arg Ser Leu Leu Ile Leu Val Leu Cys Phe Leu Pro Leu Ala Ala
1 5 10 15
Leu Gly
<210> 5
<211> 20
<212> PRT
<213> Saccharomyces cerivisae
<400> 5
Met Lys Ala Phe Thr Ser Leu Leu Cys Gly Leu Gly Leu Ser Thr Thr
1 5 10 15
Leu Ala Lys Ala
20
<210> 6
<211> 46
<212> PRT
<213> Pichia pastoris
<400> 6
Met Asp Ser Glu Pro Leu Leu Pro Asn Pro Asn Asp Ser Arg Lys Pro
1 5 10 15
Ala Asn Trp Arg Arg Ile Ile Lys Tyr Ile Ser Leu Thr Leu Ala Trp
20 25 30
Ile Gly Ile Phe Ser Tyr Val Tyr Ile Tyr His Gly Thr Ala
35 40 45
<210> 7
<211> 22
<212> PRT
<213> Saccharomyces cerevisiae
<400> 7
Met Phe Ser Leu Lys Ala Leu Leu Pro Leu Ala Leu Leu Leu Val Ser
1 5 10 15
Ala Asn Gln Val Ala Ala
20
<210> 8
<211> 19
<212> PRT
<213> Saccharomyces cerevisiae
<400> 8
Met Leu Leu Gln Ala Phe Leu Phe Leu Leu Ala Gly Phe Ala Ala Lys
1 5 10 15
Ile Ser Ala
<210> 9
<211> 20
<212> PRT
<213> Pichia pastoris
<400> 9
Met Lys Leu Ser Thr Asn Leu Ile Leu Ala Ile Ala Ala Ala Ser Ala
1 5 10 15
Val Val Ser Ala
20
<210> 10
<211> 97
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 10
Met Asp Ser Lys Gly Ser Ser Gln Lys Gly Ser Arg Leu Leu Leu Leu
1 5 10 15
Leu Val Val Ser Asn Leu Leu Leu Cys Ser Ala Ala Pro Val Asn Thr
20 25 30
Thr Thr Glu Asp Glu Thr Ala Gln Ile Pro Ala Glu Ala Val Ile Gly
35 40 45
Tyr Ser Asp Leu Glu Gly Asp Phe Asp Val Ala Val Leu Pro Phe Ser
50 55 60
Asn Ser Thr Asn Asn Gly Leu Leu Phe Ile Asn Thr Thr Ile Ala Ser
65 70 75 80
Ile Ala Ala Lys Glu Glu Gly Val Ser Leu Glu Lys Arg Glu Ala Glu
85 90 95
Ala
<210> 11
<211> 88
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 11
Met Arg Ser Leu Leu Ile Leu Val Leu Cys Phe Leu Pro Leu Ala Ala
1 5 10 15
Leu Gly Ala Pro Val Asn Thr Thr Thr Glu Asp Glu Thr Ala Gln Ile
20 25 30
Pro Ala Glu Ala Val Ile Gly Tyr Ser Asp Leu Glu Gly Asp Phe Asp
35 40 45
Val Ala Val Leu Pro Phe Ser Asn Ser Thr Asn Asn Gly Leu Leu Phe
50 55 60
Ile Asn Thr Thr Ile Ala Ser Ile Ala Ala Lys Glu Glu Gly Val Ser
65 70 75 80
Leu Glu Lys Arg Glu Ala Glu Ala
85
<210> 12
<211> 90
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 12
Met Lys Ala Phe Thr Ser Leu Leu Cys Gly Leu Gly Leu Ser Thr Thr
1 5 10 15
Leu Ala Lys Ala Ala Pro Val Asn Thr Thr Thr Glu Asp Glu Thr Ala
20 25 30
Gln Ile Pro Ala Glu Ala Val Ile Gly Tyr Ser Asp Leu Glu Gly Asp
35 40 45
Phe Asp Val Ala Val Leu Pro Phe Ser Asn Ser Thr Asn Asn Gly Leu
50 55 60
Leu Phe Ile Asn Thr Thr Ile Ala Ser Ile Ala Ala Lys Glu Glu Gly
65 70 75 80
Val Ser Leu Glu Lys Arg Glu Ala Glu Ala
85 90
<210> 13
<211> 116
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 13
Met Asp Ser Glu Pro Leu Leu Pro Asn Pro Asn Asp Ser Arg Lys Pro
1 5 10 15
Ala Asn Trp Arg Arg Ile Ile Lys Tyr Ile Ser Leu Thr Leu Ala Trp
20 25 30
Ile Gly Ile Phe Ser Tyr Val Tyr Ile Tyr His Gly Thr Ala Ala Pro
35 40 45
Val Asn Thr Thr Thr Glu Asp Glu Thr Ala Gln Ile Pro Ala Glu Ala
50 55 60
Val Ile Gly Tyr Ser Asp Leu Glu Gly Asp Phe Asp Val Ala Val Leu
65 70 75 80
Pro Phe Ser Asn Ser Thr Asn Asn Gly Leu Leu Phe Ile Asn Thr Thr
85 90 95
Ile Ala Ser Ile Ala Ala Lys Glu Glu Gly Val Ser Leu Glu Lys Arg
100 105 110
Glu Ala Glu Ala
115
<210> 14
<211> 92
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 14
Met Phe Ser Leu Lys Ala Leu Leu Pro Leu Ala Leu Leu Leu Val Ser
1 5 10 15
Ala Asn Gln Val Ala Ala Ala Pro Val Asn Thr Thr Thr Glu Asp Glu
20 25 30
Thr Ala Gln Ile Pro Ala Glu Ala Val Ile Gly Tyr Ser Asp Leu Glu
35 40 45
Gly Asp Phe Asp Val Ala Val Leu Pro Phe Ser Asn Ser Thr Asn Asn
50 55 60
Gly Leu Leu Phe Ile Asn Thr Thr Ile Ala Ser Ile Ala Ala Lys Glu
65 70 75 80
Glu Gly Val Ser Leu Glu Lys Arg Glu Ala Glu Ala
85 90
<210> 15
<211> 89
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 15
Met Leu Leu Gln Ala Phe Leu Phe Leu Leu Ala Gly Phe Ala Ala Lys
1 5 10 15
Ile Ser Ala Ala Pro Val Asn Thr Thr Thr Glu Asp Glu Thr Ala Gln
20 25 30
Ile Pro Ala Glu Ala Val Ile Gly Tyr Ser Asp Leu Glu Gly Asp Phe
35 40 45
Asp Val Ala Val Leu Pro Phe Ser Asn Ser Thr Asn Asn Gly Leu Leu
50 55 60
Phe Ile Asn Thr Thr Ile Ala Ser Ile Ala Ala Lys Glu Glu Gly Val
65 70 75 80
Ser Leu Glu Lys Arg Glu Ala Glu Ala
85
<210> 16
<211> 90
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 16
Met Lys Leu Ser Thr Asn Leu Ile Leu Ala Ile Ala Ala Ala Ser Ala
1 5 10 15
Val Val Ser Ala Ala Pro Val Asn Thr Thr Thr Glu Asp Glu Thr Ala
20 25 30
Gln Ile Pro Ala Glu Ala Val Ile Gly Tyr Ser Asp Leu Glu Gly Asp
35 40 45
Phe Asp Val Ala Val Leu Pro Phe Ser Asn Ser Thr Asn Asn Gly Leu
50 55 60
Leu Phe Ile Asn Thr Thr Ile Ala Ser Ile Ala Ala Lys Glu Glu Gly
65 70 75 80
Val Ser Leu Glu Lys Arg Glu Ala Glu Ala
85 90
<210> 17
<211> 315
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 17
Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gly Gly
1 5 10 15
Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Ser Gly Gln Gln Gly
20 25 30
Pro Gly Gly Ala Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly
35 40 45
Pro Gly Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro
50 55 60
Gly Ala Gly Gln Gln Gly Pro Gly Gly Ala Gly Gln Gln Gly Pro Gly
65 70 75 80
Ser Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Gly Gln
85 90 95
Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro
100 105 110
Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala
115 120 125
Ala Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln Arg Ser Gln Gly Pro
130 135 140
Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly
145 150 155 160
Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly
165 170 175
Pro Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr
180 185 190
Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser
195 200 205
Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala
210 215 220
Ala Ala Ala Ala Ala Ala Val Gly Gly Tyr Gly Pro Gly Ala Gly Gln
225 230 235 240
Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro
245 250 255
Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala
260 265 270
Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln
275 280 285
Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr
290 295 300
Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala
305 310 315
<210> 18
<211> 280
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 18
Gly Gly Gln Gly Gly Arg Gly Gly Phe Gly Gly Leu Gly Ser Gln Gly
1 5 10 15
Ala Gly Gly Ala Gly Gln Gly Gly Ala Gly Ala Ala Ala Ala Ala Ala
20 25 30
Ala Ala Gly Gly Asp Gly Gly Ser Gly Leu Gly Gly Tyr Gly Ala Gly
35 40 45
Arg Gly His Gly Val Gly Leu Gly Gly Ala Gly Gly Ala Gly Ala Ala
50 55 60
Ser Ala Ala Ala Ala Ala Gly Gly Gln Gly Gly Arg Gly Gly Phe Gly
65 70 75 80
Gly Leu Gly Ser Gln Gly Ala Gly Gly Ala Gly Gln Gly Gly Ala Gly
85 90 95
Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Asp Gly Gly Ser Gly Leu
100 105 110
Gly Gly Tyr Gly Ala Gly Arg Gly His Gly Ala Gly Leu Gly Gly Ala
115 120 125
Gly Gly Ala Gly Ala Ala Ser Ala Ala Ala Ala Ala Gly Gly Gln Gly
130 135 140
Gly Arg Gly Gly Phe Gly Gly Leu Gly Ser Gln Gly Ser Gly Gly Ala
145 150 155 160
Gly Gln Gly Gly Ser Gly Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly
165 170 175
Asp Gly Gly Ser Gly Leu Gly Gly Tyr Gly Ala Gly Arg Gly Tyr Gly
180 185 190
Ala Gly Leu Gly Gly Ala Gly Gly Ala Gly Ala Ala Ser Ala Ala Ala
195 200 205
Ala Ala Gly Gly Gln Gly Gly Arg Gly Gly Phe Gly Gly Leu Gly Ser
210 215 220
Gln Gly Ala Gly Gly Ala Gly Gln Gly Gly Ser Gly Ala Ala Ala Ala
225 230 235 240
Ala Ala Ala Ala Val Ala Asp Gly Gly Ser Gly Leu Gly Gly Tyr Gly
245 250 255
Ala Gly Arg Gly Tyr Gly Ala Gly Leu Gly Gly Ala Gly Gly Ala Gly
260 265 270
Ala Ala Ser Ala Ala Ala Ala Thr
275 280
<210> 19
<211> 278
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 19
Gly Ser Ala Pro Gln Gly Ala Gly Gly Pro Ala Pro Gln Gly Pro Ser
1 5 10 15
Gln Gln Gly Pro Val Ser Gln Gly Pro Tyr Gly Pro Gly Ala Ala Ala
20 25 30
Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly
35 40 45
Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Ser
50 55 60
Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro
65 70 75 80
Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr
85 90 95
Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser
100 105 110
Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala
115 120 125
Ala Ala Ala Ala Ala Ala Val Gly Gly Tyr Gly Pro Gly Ala Gly Gln
130 135 140
Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro
145 150 155 160
Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala
165 170 175
Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln
180 185 190
Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr
195 200 205
Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro
210 215 220
Gly Ala Gly Gln Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly
225 230 235 240
Gly Gln Gly Pro Tyr Gly Ser Gly Gln Gln Gly Pro Gly Gly Ala Gly
245 250 255
Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ala Ala
260 265 270
Ala Ala Ala Ala Ala Ala
275
<210> 20
<211> 261
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 20
Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gly Gly
1 5 10 15
Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Ser Gly Gln Gln Gly
20 25 30
Pro Gly Gly Ala Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly
35 40 45
Pro Gly Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro
50 55 60
Gly Ala Gly Gln Gln Gly Pro Gly Gly Ala Gly Gln Gln Gly Pro Gly
65 70 75 80
Ser Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Gly Gln
85 90 95
Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro
100 105 110
Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala
115 120 125
Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln
130 135 140
Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr
145 150 155 160
Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro
165 170 175
Gly Ala Gly Gln Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly
180 185 190
Gly Gln Gly Pro Tyr Gly Ser Gly Gln Gln Gly Pro Gly Gly Ala Gly
195 200 205
Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Gly Gly Tyr Gly Pro
210 215 220
Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly
225 230 235 240
Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala Ala Ala
245 250 255
Ala Ala Ala Ala Ala
260
<210> 21
<211> 258
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 21
Gly Pro Gly Ala Arg Arg Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser
1 5 10 15
Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Ser Gly Gln
20 25 30
Gln Gly Pro Gly Gly Ala Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro
35 40 45
Tyr Gly Pro Gly Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr
50 55 60
Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Gly Ala Gly Gln Gln Gly
65 70 75 80
Pro Gly Ser Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala
85 90 95
Gly Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln
100 105 110
Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala Ala Ala Ala Ala
115 120 125
Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro
130 135 140
Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln
145 150 155 160
Gly Pro Tyr Gly Pro Gly Ala Ala Ala Ala Ala Ala Ala Val Gly Gly
165 170 175
Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly
180 185 190
Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Ser
195 200 205
Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Ala Gly
210 215 220
Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly
225 230 235 240
Pro Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala
245 250 255
Ala Ala
<210> 22
<211> 257
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 22
Gly Pro Gly Ala Arg Arg Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser
1 5 10 15
Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Ser Gly Gln
20 25 30
Gln Gly Pro Gly Gly Ala Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro
35 40 45
Tyr Gly Pro Gly Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr
50 55 60
Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Gly Ala Gly Gln Gln Gly
65 70 75 80
Pro Gly Ser Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala
85 90 95
Gly Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln
100 105 110
Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala Ala Ala Ala Ala
115 120 125
Ala Ala Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly
130 135 140
Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly
145 150 155 160
Pro Tyr Gly Pro Gly Ala Ala Ala Ala Ala Ala Ala Val Gly Gly Tyr
165 170 175
Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser
180 185 190
Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala
195 200 205
Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln
210 215 220
Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro
225 230 235 240
Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala
245 250 255
Ala
<210> 23
<211> 255
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 23
Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gly Gly
1 5 10 15
Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Ser Gly Gln Gln Gly
20 25 30
Pro Gly Gly Ala Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly
35 40 45
Pro Gly Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro
50 55 60
Gly Ala Gly Gln Gln Gly Pro Gly Gly Ala Gly Gln Gln Gly Pro Glu
65 70 75 80
Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly
85 90 95
Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ala Ala Ala Ala Ala Ala Val
100 105 110
Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln Gly
115 120 125
Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly
130 135 140
Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly
145 150 155 160
Ala Gly Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln
165 170 175
Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala Ala Ala Ala
180 185 190
Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro
195 200 205
Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Ser
210 215 220
Gly Gln Gln Gly Pro Gly Gly Ala Gly Gln Gln Gly Pro Gly Gly Gln
225 230 235 240
Gly Pro Tyr Gly Pro Gly Ala Ala Ala Ala Ala Ala Ala Ala Ala
245 250 255
<210> 24
<211> 252
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 24
Gly Val Phe Ser Ala Gly Gln Gly Ala Thr Pro Trp Glu Asn Ser Gln
1 5 10 15
Leu Ala Glu Ser Phe Ile Ser Arg Phe Leu Arg Phe Ile Gly Gln Ser
20 25 30
Gly Ala Phe Ser Pro Asn Gln Leu Asp Asp Met Ser Ser Ile Gly Asp
35 40 45
Thr Leu Lys Thr Ala Ile Glu Lys Met Ala Gln Ser Arg Lys Ser Ser
50 55 60
Lys Ser Lys Leu Gln Ala Leu Asn Met Ala Phe Ala Ser Ser Met Ala
65 70 75 80
Glu Ile Ala Val Ala Glu Gln Gly Gly Leu Ser Leu Glu Ala Lys Thr
85 90 95
Asn Ala Ile Ala Ser Ala Leu Ser Ala Ala Phe Leu Glu Thr Thr Gly
100 105 110
Tyr Val Asn Gln Gln Phe Val Asn Glu Ile Lys Thr Leu Ile Phe Met
115 120 125
Ile Ala Gln Ala Ser Ser Asn Glu Ile Ser Gly Ser Ala Ala Ala Ala
130 135 140
Gly Gly Ser Ser Gly Gly Gly Gly Gly Ser Gly Gln Gly Gly Tyr Gly
145 150 155 160
Gln Gly Ala Tyr Ala Ser Ala Ser Ala Ala Ala Ala Tyr Gly Ser Ala
165 170 175
Pro Gln Gly Thr Gly Gly Pro Ala Ser Gln Gly Pro Ser Gln Gln Gly
180 185 190
Pro Val Ser Gln Pro Ser Tyr Gly Pro Ser Ala Thr Val Ala Val Thr
195 200 205
Ala Val Gly Gly Arg Pro Gln Gly Pro Ser Ala Pro Arg Gln Gln Gly
210 215 220
Pro Ser Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Gly Arg Gly Pro
225 230 235 240
Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala
245 250
<210> 25
<211> 252
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 25
Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala
1 5 10 15
Gly Ser Gly Ala Ser Thr Ser Val Ser Thr Ser Ser Ser Ser Gly Ser
20 25 30
Gly Ala Gly Ala Gly Ala Gly Ser Gly Ala Gly Ser Gly Ala Gly Ala
35 40 45
Gly Ser Gly Ala Gly Ala Gly Ala Gly Ala Gly Gly Ala Gly Ala Gly
50 55 60
Phe Gly Ser Gly Leu Gly Leu Gly Tyr Gly Val Gly Leu Ser Ser Ala
65 70 75 80
Gln Ala Gln Ala Gln Ala Gln Ala Ala Ala Gln Ala Gln Ala Gln Ala
85 90 95
Gln Ala Gln Ala Tyr Ala Ala Ala Gln Ala Gln Ala Gln Ala Gln Ala
100 105 110
Gln Ala Gln Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Ala
115 120 125
Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly Ser
130 135 140
Gly Ala Ser Thr Ser Val Ser Thr Ser Ser Ser Ser Gly Ser Gly Ala
145 150 155 160
Gly Ala Gly Ala Gly Ser Gly Ala Gly Ser Gly Ala Gly Ala Gly Ser
165 170 175
Gly Ala Gly Ala Gly Ala Gly Ala Gly Gly Ala Gly Ala Gly Phe Gly
180 185 190
Ser Gly Leu Gly Leu Gly Tyr Gly Val Gly Leu Ser Ser Ala Gln Ala
195 200 205
Gln Ala Gln Ala Gln Ala Ala Ala Gln Ala Gln Ala Gln Ala Gln Ala
210 215 220
Gln Ala Tyr Ala Ala Ala Gln Ala Gln Ala Gln Ala Gln Ala Gln Ala
225 230 235 240
Gln Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
245 250
<210> 26
<211> 252
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 26
Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala
1 5 10 15
Gly Ser Gly Ala Ser Thr Ser Val Ser Thr Ser Ser Ser Ser Gly Ser
20 25 30
Gly Ala Gly Ala Gly Ala Gly Ser Gly Ala Gly Ser Gly Ala Gly Ala
35 40 45
Gly Ser Gly Ala Gly Ala Gly Ala Gly Ala Gly Gly Ala Gly Ala Ala
50 55 60
Phe Gly Ser Gly Leu Gly Leu Gly Tyr Gly Val Gly Leu Ser Ser Ala
65 70 75 80
Gln Ala Gln Ala Gln Ala Gln Ala Ala Ala Gln Ala Gln Ala Asp Ala
85 90 95
Gln Ala Gln Ala Tyr Ala Ala Ala Gln Ala Gln Ala Gln Ala Gln Ala
100 105 110
Gln Ala Gln Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Ala
115 120 125
Gly Ala Gly Ala Gly Ala Gly Ser Gly Ala Gly Ala Gly Ala Gly Ser
130 135 140
Gly Ala Ser Thr Ser Val Ser Thr Ser Ser Ser Ser Gly Ser Gly Ala
145 150 155 160
Gly Ala Gly Ala Gly Ser Gly Ala Gly Ser Gly Ala Gly Ala Gly Ser
165 170 175
Gly Ala Gly Ala Gly Ala Gly Ala Gly Gly Ala Gly Ala Gly Phe Gly
180 185 190
Ser Gly Leu Gly Leu Gly Tyr Gly Val Gly Leu Ser Ser Ala Gln Ala
195 200 205
Gln Ala Gln Ala Gln Ala Ala Ala Gln Ala Gln Ala Asp Ala Gln Ala
210 215 220
Gln Ala Tyr Ala Ala Ala Gln Ala Gln Ala Gln Ala Gln Ala Gln Ala
225 230 235 240
Gln Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
245 250
<210> 27
<211> 252
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 27
Gly Ala Gly Ala Gly Ala Gly Ala Gly Ser Gly Ala Gly Ala Gly Ala
1 5 10 15
Gly Ser Gly Ala Ser Thr Ser Val Ser Thr Ser Ser Ser Ser Gly Ser
20 25 30
Gly Ala Gly Ala Gly Ala Gly Ser Gly Ala Gly Ser Gly Ala Gly Ala
35 40 45
Gly Ser Gly Ala Gly Ala Gly Ala Gly Ala Gly Gly Ala Gly Ala Gly
50 55 60
Phe Gly Ser Gly Leu Gly Leu Gly Tyr Gly Val Gly Leu Ser Ser Ala
65 70 75 80
Gln Ala Gln Ala Gln Ser Ala Ala Ala Ala Arg Ala Gln Ala Asp Ala
85 90 95
Gln Ala Gln Ala Tyr Ala Ala Ala Gln Ala Gln Ala Gln Ala Gln Ala
100 105 110
Gln Ala Gln Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Ala
115 120 125
Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly Ser
130 135 140
Gly Ala Ser Thr Ser Val Ser Thr Ser Ser Ser Ser Ala Ser Gly Ala
145 150 155 160
Gly Ala Gly Ala Gly Ser Gly Ala Gly Ser Gly Ala Gly Ala Gly Ser
165 170 175
Gly Ala Gly Ala Gly Ala Gly Ala Gly Gly Ala Gly Ala Gly Phe Gly
180 185 190
Ser Gly Leu Gly Leu Gly Tyr Gly Val Gly Leu Ser Ser Ala Gln Ala
195 200 205
Gln Ala Gln Ala Gln Ala Ala Ala Gln Ala Gln Ala Gln Ala Gln Ala
210 215 220
Gln Ala Leu Ala Ala Ala Gln Ala Gln Ala Gln Ala Gln Ala Gln Ala
225 230 235 240
Gln Ala Ala Ala Ala Thr Ala Ala Ala Ala Ala Ala
245 250
<210> 28
<211> 252
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 28
Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Gly Ala Gly
1 5 10 15
Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly
20 25 30
Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly
35 40 45
Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala Ala
50 55 60
Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln
65 70 75 80
Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly
85 90 95
Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly
100 105 110
Pro Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly
115 120 125
Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly
130 135 140
Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly
145 150 155 160
Ala Ala Ala Ala Ala Ala Ala Val Gly Gly Tyr Gly Pro Gly Ala Gly
165 170 175
Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly
180 185 190
Pro Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala
195 200 205
Ala Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser
210 215 220
Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro
225 230 235 240
Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala
245 250
<210> 29
<211> 251
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 29
Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Gly Ala Gly
1 5 10 15
Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly
20 25 30
Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly
35 40 45
Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala Ala
50 55 60
Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln
65 70 75 80
Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly
85 90 95
Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly
100 105 110
Pro Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr
115 120 125
Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser
130 135 140
Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala
145 150 155 160
Ala Ala Ala Ala Ala Ala Val Gly Gly Tyr Gly Pro Gly Ala Gly Gln
165 170 175
Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro
180 185 190
Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala
195 200 205
Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln
210 215 220
Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr
225 230 235 240
Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala
245 250
<210> 30
<211> 248
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 30
Gly His Gln Gly Pro His Arg Lys Thr Pro Trp Glu Thr Pro Glu Met
1 5 10 15
Ala Glu Asn Phe Met Asn Asn Val Arg Glu Asn Leu Glu Ala Ser Arg
20 25 30
Ile Phe Pro Asp Glu Leu Met Lys Asp Met Glu Ala Ile Thr Asn Thr
35 40 45
Met Ile Ala Ala Val Asp Gly Leu Glu Ala Gln His Arg Ser Ser Tyr
50 55 60
Ala Ser Leu Gln Ala Met Asn Thr Ala Phe Ala Ser Ser Met Ala Gln
65 70 75 80
Leu Phe Ala Thr Glu Gln Asp Tyr Val Asp Thr Glu Val Ile Ala Gly
85 90 95
Ala Ile Gly Lys Ala Tyr Gln Gln Ile Thr Gly Tyr Glu Asn Pro His
100 105 110
Leu Ala Ser Glu Val Thr Arg Leu Ile Gln Leu Phe Arg Glu Glu Asp
115 120 125
Asp Leu Glu Asn Glu Val Glu Ile Ser Phe Ala Asp Thr Asp Asn Ala
130 135 140
Ile Ala Arg Ala Ala Ala Gly Ala Ala Ala Gly Ser Ala Ala Ala Ser
145 150 155 160
Ser Ser Ala Asp Ala Ser Ala Thr Ala Glu Gly Ala Ser Gly Asp Ser
165 170 175
Gly Phe Leu Phe Ser Thr Gly Thr Phe Gly Arg Gly Gly Ala Gly Ala
180 185 190
Gly Ala Gly Ala Ala Ala Ala Ser Ala Ala Ala Ala Ser Ala Ala Ala
195 200 205
Ala Gly Ala Glu Gly Asp Arg Gly Leu Phe Phe Ser Thr Gly Asp Phe
210 215 220
Gly Arg Gly Gly Ala Gly Ala Gly Ala Gly Ala Ala Ala Ala Ser Ala
225 230 235 240
Ala Ala Ala Ser Ala Ala Ala Ala
245
<210> 31
<211> 245
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 31
Gly Gly Ala Gln Lys His Pro Ser Gly Glu Tyr Ser Val Ala Thr Ala
1 5 10 15
Ser Ala Ala Ala Thr Ser Val Thr Ser Gly Gly Ala Pro Val Gly Lys
20 25 30
Pro Gly Val Pro Ala Pro Ile Phe Tyr Pro Gln Gly Pro Leu Gln Gln
35 40 45
Gly Pro Ala Pro Gly Pro Ser Asn Val Gln Pro Gly Thr Ser Gln Gln
50 55 60
Gly Pro Ile Gly Gly Val Gly Glu Ser Asn Thr Phe Ser Ser Ser Phe
65 70 75 80
Ala Ser Ala Leu Gly Gly Asn Arg Gly Phe Ser Gly Val Ile Ser Ser
85 90 95
Ala Ser Ala Thr Ala Val Ala Ser Ala Phe Gln Lys Gly Leu Ala Pro
100 105 110
Tyr Gly Thr Ala Phe Ala Leu Ser Ala Ala Ser Ala Ala Ala Asp Ala
115 120 125
Tyr Asn Ser Ile Gly Ser Gly Ala Ser Ala Ser Ala Tyr Ala Gln Ala
130 135 140
Phe Ala Arg Val Leu Tyr Pro Leu Leu Gln Gln Tyr Gly Leu Ser Ser
145 150 155 160
Ser Ala Asp Ala Ser Ala Phe Ala Ser Ala Ile Ala Ser Ser Phe Ser
165 170 175
Thr Gly Val Ala Gly Gln Gly Pro Ser Val Pro Tyr Val Gly Gln Gln
180 185 190
Gln Pro Ser Ile Met Val Ser Ala Ala Ser Ala Ser Ala Ala Ala Ser
195 200 205
Ala Ala Ala Val Gly Gly Gly Pro Val Val Gln Gly Pro Tyr Asp Gly
210 215 220
Gly Gln Pro Gln Gln Pro Asn Ile Ala Ala Ser Ala Ala Ala Ala Ala
225 230 235 240
Thr Ala Thr Ser Ser
245
<210> 32
<211> 244
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 32
Gly Gly Gln Gly Gly Arg Gly Gly Phe Gly Gly Leu Gly Ser Gln Gly
1 5 10 15
Glu Gly Gly Ala Gly Gln Gly Gly Ala Gly Ala Ala Ala Ala Ala Ala
20 25 30
Ala Ala Gly Ala Asp Gly Gly Phe Gly Leu Gly Gly Tyr Gly Ala Gly
35 40 45
Arg Gly Tyr Gly Ala Gly Leu Gly Gly Ala Gly Gly Ala Gly Ala Ala
50 55 60
Ser Ala Ala Ala Ala Ala Gly Gly Gln Gly Gly Arg Ser Gly Phe Gly
65 70 75 80
Gly Leu Gly Ser Gln Gly Ala Gly Gly Ala Gly Gln Gly Gly Ala Gly
85 90 95
Ala Ala Ala Ala Ala Ala Ala Ala Gly Ala Asp Gly Gly Ser Gly Leu
100 105 110
Gly Gly Tyr Gly Ala Gly Arg Gly Tyr Gly Ala Ser Leu Gly Gly Ala
115 120 125
Asp Gly Ala Gly Ala Ala Ser Ala Ala Ala Ala Ala Gly Gly Gln Gly
130 135 140
Gly Arg Gly Gly Phe Gly Gly Leu Gly Ser Gln Gly Ala Gly Gly Ala
145 150 155 160
Gly Gln Gly Gly Ala Gly Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly
165 170 175
Asp Gly Gly Ser Gly Leu Gly Gly Tyr Gly Ala Gly Arg Gly Tyr Gly
180 185 190
Ala Gly Leu Gly Gly Ala Gly Gly Ala Gly Ala Ala Ser Ala Ala Ala
195 200 205
Ala Ala Gly Gly Glu Gly Gly Arg Gly Gly Phe Gly Gly Leu Gly Ser
210 215 220
Gln Gly Ala Gly Gly Ala Gly Gln Gly Gly Ser Leu Ala Ala Ala Ala
225 230 235 240
Ala Ala Ala Ala
<210> 33
<211> 244
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 33
Gly Pro Gly Gly Tyr Gly Gly Pro Gly Gln Pro Gly Pro Gly Gln Gly
1 5 10 15
Gln Tyr Gly Pro Gly Pro Gly Gln Gln Gly Pro Arg Gln Gly Gly Gln
20 25 30
Gln Gly Pro Ala Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Gly
35 40 45
Tyr Gly Gly Pro Gly Gln Gln Gly Pro Arg Gln Gly Gln Gln Gln Gly
50 55 60
Pro Ala Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Pro Arg
65 70 75 80
Gly Tyr Gly Gly Pro Gly Gln Gln Gly Pro Val Gln Gly Gly Gln Gln
85 90 95
Gly Pro Ala Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly Val Gly Gly
100 105 110
Tyr Gly Gly Pro Gly Gln Gln Gly Pro Gly Gln Gly Gln Tyr Gly Pro
115 120 125
Gly Thr Gly Gln Gln Gly Gln Gly Pro Ser Gly Gln Gln Gly Pro Ala
130 135 140
Gly Ala Ala Ala Ala Ala Ala Gly Gly Ala Ala Gly Pro Gly Gly Tyr
145 150 155 160
Gly Gly Pro Gly Gln Gln Gly Pro Gly Gln Gly Gln Tyr Gly Pro Gly
165 170 175
Thr Gly Gln Gln Gly Gln Gly Pro Ser Gly Gln Gln Gly Pro Ala Gly
180 185 190
Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Gly Tyr Gly Gly
195 200 205
Pro Gly Gln Gln Gly Pro Gly Gln Gly Gln Tyr Gly Pro Gly Ala Gly
210 215 220
Gln Gln Gly Gln Gly Pro Gly Ser Gln Gln Gly Pro Ala Ser Ala Ala
225 230 235 240
Ala Ala Ala Ala
<210> 34
<211> 243
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 34
Gly Ser Gly Ala Gly Gln Gly Thr Gly Ala Gly Ala Gly Ala Ala Ala
1 5 10 15
Ala Ala Ala Gly Ala Ala Gly Ser Gly Ala Gly Gln Gly Ala Gly Ser
20 25 30
Gly Ala Gly Ala Ala Ala Ala Ala Ala Ala Ala Ser Ala Ala Gly Ala
35 40 45
Gly Gln Gly Ala Gly Ser Gly Ser Gly Ala Gly Ala Ala Ala Ala Ala
50 55 60
Ala Ala Ala Ala Gly Ala Gly Gln Gly Ala Gly Ser Gly Ser Gly Ala
65 70 75 80
Gly Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gln Gln Gln
85 90 95
Gln Gln Gln Gln Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
100 105 110
Ala Gly Ser Gly Gln Gly Ala Ser Phe Gly Val Thr Gln Gln Phe Gly
115 120 125
Ala Pro Ser Gly Ala Ala Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala
130 135 140
Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly Gln Glu Ala Gly Thr Gly
145 150 155 160
Ala Gly Ala Ala Ala Ala Ala Ala Ala Ala Gly Ala Ala Gly Ser Gly
165 170 175
Ala Gly Gln Gly Ala Gly Ser Gly Ala Gly Ala Ala Ala Ala Ala Ala
180 185 190
Ala Ala Ala Ser Ala Ala Gly Ala Gly Gln Gly Ala Gly Ser Gly Ser
195 200 205
Gly Ala Gly Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gln
210 215 220
Gln Gln Gln Gln Gln Gln Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
225 230 235 240
Ala Ala Ala
<210> 35
<211> 242
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 35
Gly Gly Ala Gln Lys Gln Pro Ser Gly Glu Ser Ser Val Ala Thr Ala
1 5 10 15
Ser Ala Ala Ala Thr Ser Val Thr Ser Ala Gly Ala Pro Val Gly Lys
20 25 30
Pro Gly Val Pro Ala Pro Ile Phe Tyr Pro Gln Gly Pro Leu Gln Gln
35 40 45
Gly Pro Ala Pro Gly Pro Ser Tyr Val Gln Pro Ala Thr Ser Gln Gln
50 55 60
Gly Pro Ile Gly Gly Ala Gly Arg Ser Asn Ala Phe Ser Ser Ser Phe
65 70 75 80
Ala Ser Ala Leu Ser Gly Asn Arg Gly Phe Ser Glu Val Ile Ser Ser
85 90 95
Ala Ser Ala Thr Ala Val Ala Ser Ala Phe Gln Lys Gly Leu Ala Pro
100 105 110
Tyr Gly Thr Ala Phe Ala Leu Ser Ala Ala Ser Ala Ala Ala Asp Ala
115 120 125
Tyr Asn Ser Ile Gly Ser Gly Ala Asn Ala Phe Ala Tyr Ala Gln Ala
130 135 140
Phe Ala Arg Val Leu Tyr Pro Leu Val Gln Gln Tyr Gly Leu Ser Ser
145 150 155 160
Ser Ala Lys Ala Ser Ala Phe Ala Ser Ala Ile Ala Ser Ser Phe Ser
165 170 175
Ser Gly Ala Ala Gly Gln Gly Gln Ser Ile Pro Tyr Gly Gly Gln Gln
180 185 190
Gln Pro Pro Met Thr Ile Ser Ala Ala Ser Ala Ser Ala Gly Ala Ser
195 200 205
Ala Ala Ala Val Lys Gly Gly Gln Val Gly Gln Gly Pro Tyr Gly Gly
210 215 220
Gln Gln Gln Ser Thr Ala Ala Ser Ala Ser Ala Ala Ala Thr Thr Ala
225 230 235 240
Thr Ala
<210> 36
<211> 241
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 36
Gly Ala Asp Gly Gly Ser Gly Leu Gly Gly Tyr Gly Ala Gly Arg Gly
1 5 10 15
Tyr Gly Ala Gly Leu Gly Gly Ala Asp Gly Ala Gly Ala Ala Ser Ala
20 25 30
Ala Ala Ala Ala Gly Gly Gln Gly Gly Arg Gly Gly Phe Gly Arg Leu
35 40 45
Gly Ser Gln Gly Ala Gly Gly Ala Gly Gln Gly Gly Ala Gly Ala Ala
50 55 60
Ala Ala Val Ala Ala Ala Gly Gly Asp Gly Gly Ser Gly Leu Gly Gly
65 70 75 80
Tyr Gly Ala Gly Arg Gly Tyr Gly Ala Gly Leu Gly Gly Ala Gly Gly
85 90 95
Ala Gly Ala Ala Ser Ala Ala Ala Ala Ala Gly Gly Gln Gly Gly Arg
100 105 110
Gly Gly Phe Gly Gly Leu Gly Ser Gln Gly Ala Gly Gly Ala Gly Gln
115 120 125
Gly Gly Ala Gly Ala Ala Ala Ser Gly Asp Gly Gly Ser Gly Leu Gly
130 135 140
Gly Tyr Gly Ala Gly Arg Gly Tyr Gly Ala Gly Leu Gly Gly Ala Asp
145 150 155 160
Gly Ala Gly Ala Ala Ser Ala Ala Ser Ala Ala Gly Gly Gln Gly Gly
165 170 175
Arg Gly Gly Phe Gly Gly Leu Gly Ser Gln Gly Ala Gly Gly Ala Gly
180 185 190
Gln Gly Gly Ala Gly Ala Ala Ala Ala Ala Ala Thr Ala Gly Gly Asp
195 200 205
Gly Gly Ser Gly Leu Gly Gly Tyr Gly Ala Gly Arg Gly Tyr Gly Ala
210 215 220
Gly Leu Gly Gly Ala Gly Gly Ala Gly Ala Ala Ser Ala Ala Ala Ala
225 230 235 240
Ala
<210> 37
<211> 241
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 37
Gly Ala Gly Ala Gly Gln Gly Gly Arg Gly Gly Tyr Gly Gln Gly Gly
1 5 10 15
Phe Gly Gly Gln Gly Ser Gly Ala Gly Ala Gly Ala Ser Ala Ala Ala
20 25 30
Gly Ala Gly Ala Gly Gln Gly Gly Arg Gly Gly Tyr Gly Gln Gly Gly
35 40 45
Phe Gly Gly Gln Gly Ser Gly Ala Gly Ala Gly Ala Ser Ala Ala Ala
50 55 60
Gly Ala Gly Ala Gly Gln Gly Gly Arg Gly Gly Tyr Gly Gln Gly Gly
65 70 75 80
Phe Gly Gly Gln Gly Ser Gly Ala Gly Ala Gly Ala Ser Ala Ala Ala
85 90 95
Ala Ala Gly Ala Gly Gln Gly Gly Arg Gly Gly Tyr Gly Gln Gly Gly
100 105 110
Leu Gly Gly Ser Gly Ser Gly Ala Gly Ala Gly Ala Gly Ala Ala Ala
115 120 125
Ala Ala Ala Ala Gly Ala Gly Gly Tyr Gly Gln Gly Gly Leu Gly Gly
130 135 140
Tyr Gly Gln Gly Ala Gly Ala Gly Gln Gly Gly Leu Gly Gly Tyr Gly
145 150 155 160
Ser Gly Ala Gly Ala Gly Ala Ser Ala Ala Ala Ala Ala Gly Ala Gly
165 170 175
Gly Ala Gly Gln Gly Gly Leu Gly Gly Tyr Gly Gln Gly Ala Gly Ala
180 185 190
Gly Gln Gly Gly Leu Gly Gly Tyr Gly Ser Gly Ala Gly Ala Gly Ala
195 200 205
Ala Ala Ala Ala Ala Ala Gly Ala Gly Gly Ser Gly Gln Gly Gly Leu
210 215 220
Gly Gly Tyr Gly Ser Gly Gly Gly Ala Gly Gly Ala Ser Ala Ala Ala
225 230 235 240
Ala
<210> 38
<211> 239
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 38
Gly Ala Tyr Ala Tyr Ala Tyr Ala Ile Ala Asn Ala Phe Ala Ser Ile
1 5 10 15
Leu Ala Asn Thr Gly Leu Leu Ser Val Ser Ser Ala Ala Ser Val Ala
20 25 30
Ser Ser Val Ala Ser Ala Ile Ala Thr Ser Val Ser Ser Ser Ser Ala
35 40 45
Ala Ala Ala Ala Ser Ala Ser Ala Ala Ala Ala Ala Ser Ala Gly Ala
50 55 60
Ser Ala Ala Ser Ser Ala Ser Ala Ser Ser Ser Ala Ser Ala Ala Ala
65 70 75 80
Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Ser Gly Ala Ser Gly Ala
85 90 95
Ala Gly Gly Ser Gly Gly Phe Gly Leu Ser Ser Gly Phe Gly Ala Gly
100 105 110
Ile Gly Gly Leu Gly Gly Tyr Pro Ser Gly Ala Leu Gly Gly Leu Gly
115 120 125
Ile Pro Ser Gly Leu Leu Ser Ser Gly Leu Leu Ser Pro Ala Ala Asn
130 135 140
Gln Arg Ile Ala Ser Leu Ile Pro Leu Ile Leu Ser Ala Ile Ser Pro
145 150 155 160
Asn Gly Val Asn Phe Gly Val Ile Gly Ser Asn Ile Ala Ser Leu Ala
165 170 175
Ser Gln Ile Ser Gln Ser Gly Gly Gly Ile Ala Ala Ser Gln Ala Phe
180 185 190
Thr Gln Ala Leu Leu Glu Leu Val Ala Ala Phe Ile Gln Val Leu Ser
195 200 205
Ser Ala Gln Ile Gly Ala Val Ser Ser Ser Ser Ala Ser Ala Gly Ala
210 215 220
Thr Ala Asn Ala Phe Ala Gln Ser Leu Ser Ser Ala Phe Ala Gly
225 230 235
<210> 39
<211> 239
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 39
Gly Ala Ala Gln Lys Gln Pro Ser Gly Glu Ser Ser Val Ala Thr Ala
1 5 10 15
Ser Ala Ala Ala Thr Ser Val Thr Ser Gly Gly Ala Pro Val Gly Lys
20 25 30
Pro Gly Val Pro Ala Pro Ile Phe Tyr Pro Gln Gly Pro Leu Gln Gln
35 40 45
Gly Pro Ala Pro Gly Pro Ser Asn Val Gln Pro Gly Thr Ser Gln Gln
50 55 60
Gly Pro Ile Gly Gly Val Gly Gly Ser Asn Ala Phe Ser Ser Ser Phe
65 70 75 80
Ala Ser Ala Leu Ser Leu Asn Arg Gly Phe Thr Glu Val Ile Ser Ser
85 90 95
Ala Ser Ala Thr Ala Val Ala Ser Ala Phe Gln Lys Gly Leu Ala Pro
100 105 110
Tyr Gly Thr Ala Phe Ala Leu Ser Ala Ala Ser Ala Ala Ala Asp Ala
115 120 125
Tyr Asn Ser Ile Gly Ser Gly Ala Asn Ala Phe Ala Tyr Ala Gln Ala
130 135 140
Phe Ala Arg Val Leu Tyr Pro Leu Val Arg Gln Tyr Gly Leu Ser Ser
145 150 155 160
Ser Gly Lys Ala Ser Ala Phe Ala Ser Ala Ile Ala Ser Ser Phe Ser
165 170 175
Ser Gly Thr Ser Gly Gln Gly Pro Ser Ile Gly Gln Gln Gln Pro Pro
180 185 190
Val Thr Ile Ser Ala Ala Ser Ala Ser Ala Gly Ala Ser Ala Ala Ala
195 200 205
Val Gly Gly Gly Gln Val Gly Gln Gly Pro Tyr Gly Gly Gln Gln Gln
210 215 220
Ser Thr Ala Ala Ser Ala Ser Ala Ala Ala Ala Thr Ala Thr Ser
225 230 235
<210> 40
<211> 239
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 40
Gly Ala Ala Gln Lys Gln Pro Ser Gly Glu Ser Ser Val Ala Thr Ala
1 5 10 15
Ser Ala Ala Ala Thr Ser Val Thr Ser Gly Gly Ala Pro Val Gly Lys
20 25 30
Pro Gly Val Pro Ala Pro Ile Phe Tyr Pro Gln Gly Pro Leu Gln Gln
35 40 45
Gly Pro Ala Pro Gly Pro Ser Asn Val Gln Pro Gly Thr Ser Gln Gln
50 55 60
Gly Pro Ile Gly Gly Val Gly Gly Ser Asn Ala Phe Ser Ser Ser Phe
65 70 75 80
Ala Ser Ala Leu Ser Leu Asn Arg Gly Phe Thr Glu Val Ile Ser Ser
85 90 95
Ala Ser Ala Thr Ala Val Ala Ser Ala Phe Gln Lys Gly Leu Ala Pro
100 105 110
Tyr Gly Thr Ala Phe Ala Leu Ser Ala Ala Ser Ala Ala Ala Asp Ala
115 120 125
Tyr Asn Ser Ile Gly Ser Gly Ala Asn Ala Phe Ala Tyr Ala Gln Ala
130 135 140
Phe Ala Arg Val Leu Tyr Pro Leu Val Arg Gln Tyr Gly Leu Ser Ser
145 150 155 160
Ser Gly Lys Ala Ser Ala Phe Ala Ser Ala Ile Ala Ser Ser Phe Ser
165 170 175
Ser Gly Thr Ser Gly Gln Gly Pro Ser Ile Gly Gln Gln Gln Pro Pro
180 185 190
Val Thr Ile Ser Ala Ala Ser Ala Ser Ala Gly Ala Ser Ala Ala Ala
195 200 205
Val Gly Gly Gly Gln Val Gly Gln Gly Pro Tyr Gly Gly Gln Gln Gln
210 215 220
Ser Thr Ala Ala Ser Ala Ser Ala Ala Ala Ala Thr Ala Thr Ser
225 230 235
<210> 41
<211> 239
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 41
Gly Ala Ala Gln Lys Gln Pro Ser Gly Glu Ser Ser Val Ala Thr Ala
1 5 10 15
Ser Ala Ala Ala Thr Ser Val Thr Ser Gly Gly Ala Pro Val Gly Lys
20 25 30
Pro Gly Val Pro Ala Pro Ile Phe Tyr Pro Gln Gly Pro Leu Gln Gln
35 40 45
Gly Pro Ala Pro Gly Pro Ser Asn Val Gln Pro Gly Thr Ser Gln Gln
50 55 60
Gly Pro Ile Gly Gly Val Gly Gly Ser Asn Ala Phe Ser Ser Ser Phe
65 70 75 80
Ala Ser Ala Leu Ser Leu Asn Arg Gly Phe Thr Glu Val Ile Ser Ser
85 90 95
Ala Ser Ala Thr Ala Val Ala Ser Ala Phe Gln Lys Gly Leu Ala Pro
100 105 110
Tyr Gly Thr Ala Phe Ala Leu Ser Ala Ala Ser Ala Ala Ala Asp Ala
115 120 125
Tyr Asn Ser Ile Gly Ser Gly Ala Asn Ala Phe Ala Tyr Ala Gln Ala
130 135 140
Phe Ala Arg Val Leu Tyr Pro Leu Val Gln Gln Tyr Gly Leu Ser Ser
145 150 155 160
Ser Ala Lys Ala Ser Ala Phe Ala Ser Ala Ile Ala Ser Ser Phe Ser
165 170 175
Ser Gly Thr Ser Gly Gln Gly Pro Ser Ile Gly Gln Gln Gln Pro Pro
180 185 190
Val Thr Ile Ser Ala Ala Ser Ala Ser Ala Gly Ala Ser Ala Ala Ala
195 200 205
Val Gly Gly Gly Gln Val Gly Gln Gly Pro Tyr Gly Gly Gln Gln Gln
210 215 220
Ser Thr Ala Ala Ser Ala Ser Ala Ala Ala Ala Thr Ala Thr Ser
225 230 235
<210> 42
<211> 239
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 42
Gly Gly Ala Gln Lys Gln Pro Ser Gly Glu Ser Ser Val Ala Thr Ala
1 5 10 15
Ser Ala Ala Ala Thr Ser Val Thr Ser Ala Gly Ala Pro Val Gly Lys
20 25 30
Pro Gly Val Pro Ala Pro Ile Phe Tyr Pro Gln Gly Pro Leu Gln Gln
35 40 45
Gly Pro Ala Pro Gly Pro Ser Asn Val Gln Pro Gly Thr Ser Gln Gln
50 55 60
Gly Pro Ile Gly Gly Val Gly Gly Ser Asn Ala Phe Ser Ser Ser Phe
65 70 75 80
Ala Ser Ala Leu Ser Leu Asn Arg Gly Phe Thr Glu Val Ile Ser Ser
85 90 95
Ala Ser Ala Thr Ala Val Ala Ser Ala Phe Gln Lys Gly Leu Ala Pro
100 105 110
Tyr Gly Thr Ala Phe Ala Leu Ser Ala Ala Ser Ala Ala Ala Asp Ala
115 120 125
Tyr Asn Ser Ile Gly Ser Gly Ala Asn Ala Phe Ala Tyr Ala Gln Ala
130 135 140
Phe Ala Arg Val Leu Tyr Pro Leu Val Gln Gln Tyr Gly Leu Ser Ser
145 150 155 160
Ser Ala Lys Ala Ser Ala Phe Ala Ser Ala Ile Ala Ser Ser Phe Ser
165 170 175
Ser Gly Thr Ser Gly Gln Gly Pro Ser Asn Gly Gln Gln Gln Pro Pro
180 185 190
Val Thr Ile Ser Ala Ala Ser Ala Ser Ala Gly Ala Ser Ala Ala Ala
195 200 205
Val Gly Gly Gly Gln Val Ser Gln Gly Pro Tyr Gly Gly Gln Gln Gln
210 215 220
Ser Thr Ala Ala Ser Ala Ser Ala Ala Ala Ala Thr Ala Thr Ser
225 230 235
<210> 43
<211> 239
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 43
Gly Gly Ala Gln Lys Gln Pro Ser Gly Glu Ser Ser Val Ala Thr Ala
1 5 10 15
Ser Ala Ala Ala Thr Ser Val Thr Ser Ala Gly Ala Pro Gly Gly Lys
20 25 30
Pro Gly Val Pro Ala Pro Ile Phe Tyr Pro Gln Gly Pro Leu Gln Gln
35 40 45
Gly Pro Ala Pro Gly Pro Ser Asn Val Gln Pro Gly Thr Ser Gln Gln
50 55 60
Gly Pro Ile Gly Gly Val Gly Gly Ser Asn Ala Phe Ser Ser Ser Phe
65 70 75 80
Ala Ser Ala Leu Ser Leu Asn Arg Gly Phe Thr Glu Val Ile Ser Ser
85 90 95
Ala Ser Ala Thr Ala Val Ala Ser Ala Phe Gln Lys Gly Leu Ala Pro
100 105 110
Tyr Gly Thr Ala Phe Ala Leu Ser Ala Ala Ser Ala Ala Ala Asp Ala
115 120 125
Tyr Asn Ser Ile Gly Ser Gly Ala Asn Ala Phe Ala Tyr Ala Gln Ala
130 135 140
Phe Ala Arg Val Leu Tyr Pro Leu Val Gln Gln Tyr Gly Leu Ser Ser
145 150 155 160
Ser Ala Lys Ala Ser Ala Phe Ala Ser Ala Ile Ala Ser Ser Phe Ser
165 170 175
Ser Gly Thr Ser Gly Gln Gly Pro Ser Ile Gly Gln Gln Gln Pro Pro
180 185 190
Val Thr Ile Ser Ala Ala Ser Ala Ser Ala Gly Ala Ser Ala Ala Ala
195 200 205
Val Gly Gly Gly Gln Val Gly Gln Gly Pro Tyr Gly Gly Gln Gln Gln
210 215 220
Ser Thr Ala Ala Ser Ala Ser Ala Ala Ala Ala Thr Ala Thr Ser
225 230 235
<210> 44
<211> 236
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 44
Gly Pro Gly Gly Tyr Gly Gly Pro Gly Gln Gln Gly Pro Gly Gln Gly
1 5 10 15
Gln Gln Gln Gly Pro Ala Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly
20 25 30
Pro Gly Gly Tyr Gly Gly Pro Gly Gln Gln Gly Pro Gly Gln Gly Gln
35 40 45
Gln Gln Gly Pro Ala Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly
50 55 60
Pro Gly Gly Tyr Gly Gly Pro Gly Gln Gln Arg Pro Gly Gln Ala Gln
65 70 75 80
Tyr Gly Arg Gly Thr Gly Gln Gln Gly Gln Gly Pro Gly Ala Gln Gln
85 90 95
Gly Pro Ala Ser Ala Ala Ala Ala Ala Ala Ala Gly Ala Gly Leu Tyr
100 105 110
Gly Gly Pro Gly Gln Gln Gly Pro Gly Gln Gly Gln Gln Gln Gly Pro
115 120 125
Ala Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly
130 135 140
Gly Tyr Gly Gly Pro Gly Gln Gln Gly Pro Gly Gln Ala Gln Gln Gln
145 150 155 160
Gly Pro Ala Ser Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Gly Tyr
165 170 175
Ser Gly Pro Gly Gln Gln Gly Pro Gly Gln Ala Gln Gln Gln Gly Pro
180 185 190
Ala Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Gly Tyr
195 200 205
Gly Gly Pro Gly Gln Gln Gly Pro Gly Gln Gly Gln Gln Gln Gly Pro
210 215 220
Ala Ser Ala Ala Ala Ala Ala Ala Ala Thr Ala Ala
225 230 235
<210> 45
<211> 234
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 45
Gly Ala Gly Gly Asp Gly Gly Leu Phe Leu Ser Ser Gly Asp Phe Gly
1 5 10 15
Arg Gly Gly Ala Gly Ala Gly Ala Gly Ala Ala Ala Ala Ser Ala Ala
20 25 30
Ala Ala Ser Ser Ala Ala Ala Gly Ala Arg Gly Gly Ser Gly Phe Gly
35 40 45
Val Gly Thr Gly Gly Phe Gly Arg Gly Gly Ala Gly Asp Gly Ala Ser
50 55 60
Ala Ala Ala Ala Ser Ala Ala Ala Ala Ser Ala Ala Ala Ala Gly Ala
65 70 75 80
Gly Gly Asp Ser Gly Leu Phe Leu Ser Ser Gly Asp Phe Gly Arg Gly
85 90 95
Gly Ala Gly Ala Gly Ala Gly Ala Ala Ala Ala Ser Ala Ala Ala Ala
100 105 110
Ser Ala Ala Ala Ala Gly Thr Gly Gly Val Gly Gly Leu Phe Leu Ser
115 120 125
Ser Gly Asp Phe Gly Arg Gly Gly Ala Gly Ala Gly Ala Gly Ala Ala
130 135 140
Ala Ala Ser Ala Ala Ala Ala Ser Ser Ala Ala Ala Gly Ala Arg Gly
145 150 155 160
Gly Ser Gly Phe Gly Val Gly Thr Gly Gly Phe Gly Arg Gly Gly Pro
165 170 175
Gly Ala Gly Thr Gly Ala Ala Ala Ala Ser Ala Ala Ala Ala Ser Ala
180 185 190
Ala Ala Ala Gly Ala Gly Gly Asp Ser Gly Leu Phe Leu Ser Ser Glu
195 200 205
Asp Phe Gly Arg Gly Gly Ala Gly Ala Gly Thr Gly Ala Ala Ala Ala
210 215 220
Ser Ala Ala Ala Ala Ser Ala Ala Ala Ala
225 230
<210> 46
<211> 233
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 46
Gly Ala Gly Arg Gly Tyr Gly Gly Gly Tyr Gly Gly Gly Ala Ala Ala
1 5 10 15
Gly Ala Gly Ala Gly Ala Gly Ala Gly Arg Gly Tyr Gly Gly Gly Tyr
20 25 30
Gly Gly Gly Ala Gly Ser Gly Ala Gly Ser Gly Ala Gly Ala Gly Gly
35 40 45
Gly Ser Gly Tyr Gly Arg Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala
50 55 60
Ala Ala Ala Ala Gly Ala Gly Ala Gly Gly Ala Gly Gly Tyr Gly Gly
65 70 75 80
Gly Ala Gly Ala Gly Ala Gly Ala Ser Ala Ala Ala Gly Ala Gly Ala
85 90 95
Gly Ala Gly Gly Ala Gly Gly Tyr Gly Gly Gly Tyr Gly Gly Gly Ala
100 105 110
Gly Ala Gly Ala Gly Ala Gly Ala Ala Ala Ala Ala Gly Ala Gly Ala
115 120 125
Gly Ala Gly Ala Gly Arg Gly Tyr Gly Gly Gly Phe Gly Gly Gly Ala
130 135 140
Gly Ser Gly Ala Gly Ala Gly Ala Gly Ala Gly Gly Gly Ser Gly Tyr
145 150 155 160
Gly Arg Gly Ala Gly Gly Tyr Gly Gly Gly Tyr Gly Gly Gly Ala Gly
165 170 175
Thr Gly Ala Gly Ala Ala Ala Ala Thr Gly Ala Gly Ala Gly Ala Gly
180 185 190
Ala Gly Arg Gly Tyr Gly Gly Gly Tyr Gly Gly Gly Ala Gly Ala Gly
195 200 205
Ala Gly Ala Gly Ala Gly Ala Gly Gly Gly Ser Gly Tyr Gly Arg Gly
210 215 220
Ala Gly Ala Gly Ala Ser Val Ala Ala
225 230
<210> 47
<211> 231
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 47
Gly Ala Leu Gly Gln Gly Ala Ser Val Trp Ser Ser Pro Gln Met Ala
1 5 10 15
Glu Asn Phe Met Asn Gly Phe Ser Met Ala Leu Ser Gln Ala Gly Ala
20 25 30
Phe Ser Gly Gln Glu Met Lys Asp Phe Asp Asp Val Arg Asp Ile Met
35 40 45
Asn Ser Ala Met Asp Lys Met Ile Arg Ser Gly Lys Ser Gly Arg Gly
50 55 60
Ala Met Arg Ala Met Asn Ala Ala Phe Gly Ser Ala Ile Ala Glu Ile
65 70 75 80
Val Ala Ala Asn Gly Gly Lys Glu Tyr Gln Ile Gly Ala Val Leu Asp
85 90 95
Ala Val Thr Asn Thr Leu Leu Gln Leu Thr Gly Asn Ala Asp Asn Gly
100 105 110
Phe Leu Asn Glu Ile Ser Arg Leu Ile Thr Leu Phe Ser Ser Val Glu
115 120 125
Ala Asn Asp Val Ser Ala Ser Ala Gly Ala Asp Ala Ser Gly Ser Ser
130 135 140
Gly Pro Val Gly Gly Tyr Ser Ser Gly Ala Gly Ala Ala Val Gly Gln
145 150 155 160
Gly Thr Ala Gln Ala Val Gly Tyr Gly Gly Gly Ala Gln Gly Val Ala
165 170 175
Ser Ser Ala Ala Ala Gly Ala Thr Asn Tyr Ala Gln Gly Val Ser Thr
180 185 190
Gly Ser Thr Gln Asn Val Ala Thr Ser Thr Val Thr Thr Thr Thr Asn
195 200 205
Val Ala Gly Ser Thr Ala Thr Gly Tyr Asn Thr Gly Tyr Gly Ile Gly
210 215 220
Ala Ala Ala Gly Ala Ala Ala
225 230
<210> 48
<211> 231
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 48
Gly Gly Gln Gly Gly Gln Gly Gly Tyr Asp Gly Leu Gly Ser Gln Gly
1 5 10 15
Ala Gly Gln Gly Gly Tyr Gly Gln Gly Gly Ala Ala Ala Ala Ala Ala
20 25 30
Ala Ala Ser Gly Ala Gly Ser Ala Gln Arg Gly Gly Leu Gly Ala Gly
35 40 45
Gly Ala Gly Gln Gly Tyr Gly Ala Gly Ser Gly Gly Gln Gly Gly Ala
50 55 60
Gly Gln Gly Gly Ala Ala Ala Ala Thr Ala Ala Ala Ala Gly Gly Gln
65 70 75 80
Gly Gly Gln Gly Gly Tyr Gly Gly Leu Gly Ser Gln Gly Ser Gly Gln
85 90 95
Gly Gly Tyr Gly Gln Gly Gly Ala Ala Ala Ala Ala Ala Ala Ala Ser
100 105 110
Gly Asp Gly Gly Ala Gly Gln Glu Gly Leu Gly Ala Gly Gly Ala Gly
115 120 125
Gln Gly Tyr Gly Ala Gly Leu Gly Gly Gln Gly Gly Ala Gly Gln Gly
130 135 140
Gly Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Gln Gly Gly Gln
145 150 155 160
Gly Gly Tyr Gly Gly Leu Gly Ser Gln Gly Ala Gly Gln Gly Gly Tyr
165 170 175
Gly Gln Gly Gly Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala Gly
180 185 190
Gly Ala Gly Gln Gly Gly Leu Gly Ala Ala Gly Ala Gly Gln Gly Tyr
195 200 205
Gly Ala Gly Ser Gly Gly Gln Gly Gly Ala Gly Gln Gly Gly Ala Ala
210 215 220
Ala Ala Ala Ala Ala Ala Ala
225 230
<210> 49
<211> 231
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 49
Gly Gly Gln Gly Gly Gln Gly Gly Tyr Gly Gly Leu Gly Ser Gln Gly
1 5 10 15
Ala Gly Gln Gly Gly Tyr Gly Gln Gly Gly Val Ala Ala Ala Ala Ala
20 25 30
Ala Ala Ser Gly Ala Gly Gly Ala Gly Arg Gly Gly Leu Gly Ala Gly
35 40 45
Gly Ala Gly Gln Glu Tyr Gly Ala Val Ser Gly Gly Gln Gly Gly Ala
50 55 60
Gly Gln Gly Gly Glu Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Gln
65 70 75 80
Gly Gly Gln Gly Gly Tyr Gly Gly Leu Gly Ser Gln Gly Ala Gly Gln
85 90 95
Gly Gly Tyr Gly Gln Gly Gly Ala Ala Ala Ala Ala Ala Ala Ala Ser
100 105 110
Gly Ala Gly Gly Ala Arg Arg Gly Gly Leu Gly Ala Gly Gly Ala Gly
115 120 125
Gln Gly Tyr Gly Ala Gly Leu Gly Gly Gln Gly Gly Ala Gly Gln Gly
130 135 140
Ser Ala Ser Ala Ala Ala Ala Ala Ala Ala Gly Gly Gln Gly Gly Gln
145 150 155 160
Gly Gly Tyr Gly Gly Leu Gly Ser Gln Gly Ser Gly Gln Gly Gly Tyr
165 170 175
Gly Gln Gly Gly Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly Ala Gly
180 185 190
Gly Ala Gly Arg Gly Ser Leu Gly Ala Gly Gly Ala Gly Gln Gly Tyr
195 200 205
Gly Ala Gly Leu Gly Gly Gln Gly Gly Ala Gly Gln Gly Gly Ala Ala
210 215 220
Ala Ala Ala Ser Ala Ala Ala
225 230
<210> 50
<211> 229
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 50
Gly Pro Gly Gly Tyr Gly Gly Pro Gly Gln Gln Gly Pro Gly Gln Gly
1 5 10 15
Gln Tyr Gly Pro Gly Thr Gly Gln Gln Gly Gln Gly Pro Gly Gly Gln
20 25 30
Gln Gly Pro Val Gly Ala Ala Ala Ala Ala Ala Ala Ala Val Ser Ser
35 40 45
Gly Gly Tyr Gly Ser Gln Gly Ala Gly Gln Gly Gly Gln Gln Gly Ser
50 55 60
Gly Gln Arg Gly Pro Ala Ala Ala Gly Pro Gly Gly Tyr Ser Gly Pro
65 70 75 80
Gly Gln Gln Gly Pro Gly Gln Gly Gly Gln Gln Gly Pro Ala Ser Ala
85 90 95
Ala Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Gly Tyr Gly Gly Ser
100 105 110
Gly Gln Gln Gly Pro Gly Gln Gly Arg Gly Thr Gly Gln Gln Gly Gln
115 120 125
Gly Pro Gly Gly Gln Gln Gly Pro Ala Ser Ala Ala Ala Ala Ala Ala
130 135 140
Ala Gly Pro Gly Gly Tyr Gly Gly Pro Gly Gln Gln Gly Pro Gly Gln
145 150 155 160
Gly Gln Tyr Gly Pro Gly Thr Gly Gln Gln Gly Gln Gly Pro Ala Ser
165 170 175
Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly Gly Tyr Gly Gly Pro Gly
180 185 190
Gln Gln Gly Pro Gly Gln Gly Gln Tyr Gly Pro Gly Thr Gly Gln Gln
195 200 205
Gly Gln Gly Pro Gly Gly Gln Gln Gly Pro Gly Gly Ala Ser Ala Ala
210 215 220
Ala Ala Ala Ala Ala
225
<210> 51
<211> 228
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 51
Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gly Gly
1 5 10 15
Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Ser Gly Gln Gln Gly
20 25 30
Pro Gly Gly Ala Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly
35 40 45
Pro Gly Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro
50 55 60
Gly Ala Gly Gln Gln Gly Pro Gly Gly Ala Gly Gln Gln Gly Pro Gly
65 70 75 80
Ser Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Gly Gln
85 90 95
Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro
100 105 110
Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala
115 120 125
Ala Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln Arg Ser Gln Gly Pro
130 135 140
Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly
145 150 155 160
Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly
165 170 175
Pro Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly Pro Gly
180 185 190
Ala Gly Arg Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln
195 200 205
Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala Ala Ala Ala
210 215 220
Ala Ala Ala Ala
225
<210> 52
<211> 225
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 52
Gly Gln Gly Gly Gln Gly Gly Gln Gly Gly Leu Gly Gln Gly Gly Tyr
1 5 10 15
Gly Gln Gly Ala Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala
20 25 30
Ala Ala Ala Ala Ala Gly Arg Gly Gln Gly Gly Tyr Gly Gln Gly Ser
35 40 45
Gly Gly Asn Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser
50 55 60
Gly Gln Gly Ser Gln Gly Gly Gln Gly Gly Gln Gly Gln Gly Gly Tyr
65 70 75 80
Gly Gln Gly Ala Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala
85 90 95
Ala Ala Ala Ala Ser Gly Arg Gly Gln Gly Gly Tyr Gly Gln Gly Ala
100 105 110
Gly Gly Asn Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
115 120 125
Ala Gly Gln Gly Gly Gln Gly Gly Tyr Gly Gly Leu Gly Gln Gly Gly
130 135 140
Tyr Gly Gln Gly Ala Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala
145 150 155 160
Ala Ala Ala Ala Gly Gly Gln Gly Gly Gln Gly Gln Gly Gly Tyr Gly
165 170 175
Gln Gly Ser Gly Gly Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
180 185 190
Ala Ala Ala Ala Ala Gly Arg Gly Gln Gly Gly Tyr Gly Gln Gly Ser
195 200 205
Gly Gly Asn Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
210 215 220
Ala
225
<210> 53
<211> 225
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 53
Gly Arg Gly Pro Gly Gly Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gly
1 5 10 15
Pro Gly Ala Ala Ala Ala Ala Ala Gly Pro Gly Gly Tyr Gly Pro Gly
20 25 30
Gly Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gly Pro Gly Ala Ala Ala
35 40 45
Ala Ala Ala Ala Gly Arg Gly Pro Gly Gly Tyr Gly Pro Gly Gln Gln
50 55 60
Gly Pro Gly Gln Gln Gly Pro Gly Gly Ser Gly Ala Ala Ala Ala Ala
65 70 75 80
Ala Gly Arg Gly Pro Gly Gly Tyr Gly Pro Gly Gln Gln Gly Pro Gly
85 90 95
Gly Pro Gly Ala Ala Ala Ala Ala Ala Gly Pro Gly Gly Tyr Gly Pro
100 105 110
Gly Gln Gln Gly Pro Gly Ala Ala Ala Ala Ala Ala Ala Ala Gly Arg
115 120 125
Gly Pro Gly Gly Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gly Pro Gly
130 135 140
Ala Ala Ala Ala Ala Ala Ala Gly Arg Gly Pro Gly Gly Tyr Gly Pro
145 150 155 160
Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Gly Gly Ser Gly Ala Ala
165 170 175
Ala Ala Ala Ala Gly Arg Gly Pro Gly Gly Tyr Gly Pro Gly Gln Gln
180 185 190
Gly Pro Gly Gly Pro Gly Ala Ala Ala Ala Ala Ala Gly Pro Gly Gly
195 200 205
Tyr Gly Pro Gly Gln Gln Gly Pro Gly Ala Ala Ala Ala Ala Ala Ala
210 215 220
Ala
225
<210> 54
<211> 225
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 54
Gly Arg Gly Pro Gly Gly Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gly
1 5 10 15
Ser Gly Ala Ala Ala Ala Ala Ala Gly Arg Gly Pro Gly Gly Tyr Gly
20 25 30
Pro Gly Gln Gln Gly Pro Gly Gly Pro Gly Ala Ala Ala Ala Ala Ala
35 40 45
Gly Pro Gly Gly Tyr Gly Pro Gly Gln Gln Gly Thr Gly Ala Ala Ala
50 55 60
Ala Ala Ala Ala Gly Ser Gly Ala Gly Gly Tyr Gly Pro Gly Gln Gln
65 70 75 80
Gly Pro Gly Gly Pro Gly Ala Ala Ala Ala Ala Ala Gly Pro Gly Gly
85 90 95
Tyr Gly Pro Gly Gln Gln Gly Pro Gly Ala Ala Ala Ala Ala Ala Ala
100 105 110
Gly Ser Gly Pro Gly Gly Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gly
115 120 125
Ser Ser Ala Ala Ala Ala Ala Ala Gly Pro Gly Arg Tyr Gly Pro Gly
130 135 140
Gln Gln Gly Pro Gly Ala Ala Ala Ala Ala Ser Ala Gly Arg Gly Pro
145 150 155 160
Gly Gly Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gly Pro Gly Ala Ala
165 170 175
Ala Ala Ala Ala Gly Pro Gly Gly Tyr Gly Pro Gly Gln Gln Gly Pro
180 185 190
Gly Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly Pro Gly Gly Tyr Gly
195 200 205
Pro Gly Gln Gln Gly Pro Gly Gly Pro Gly Ala Ala Ala Ala Ala Ala
210 215 220
Ala
225
<210> 55
<211> 219
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 55
Gly Ala Ala Ala Thr Ala Gly Ala Gly Ala Ser Val Ala Gly Gly Tyr
1 5 10 15
Gly Gly Gly Ala Gly Ala Ala Ala Gly Ala Gly Ala Gly Gly Tyr Gly
20 25 30
Gly Gly Tyr Gly Ala Val Ala Gly Ser Gly Ala Gly Ala Ala Ala Ala
35 40 45
Ala Ser Ser Gly Ala Gly Gly Ala Ala Gly Tyr Gly Arg Gly Tyr Gly
50 55 60
Ala Gly Ser Gly Ala Gly Ala Gly Ala Gly Thr Val Ala Ala Tyr Gly
65 70 75 80
Gly Ala Gly Gly Val Ala Thr Ser Ser Ser Ser Ala Thr Ala Ser Gly
85 90 95
Ser Arg Ile Val Thr Ser Gly Gly Tyr Gly Tyr Gly Thr Ser Ala Ala
100 105 110
Ala Gly Ala Gly Val Ala Ala Gly Ser Tyr Ala Gly Ala Val Asn Arg
115 120 125
Leu Ser Ser Ala Glu Ala Ala Ser Arg Val Ser Ser Asn Ile Ala Ala
130 135 140
Ile Ala Ser Gly Gly Ala Ser Ala Leu Pro Ser Val Ile Ser Asn Ile
145 150 155 160
Tyr Ser Gly Val Val Ala Ser Gly Val Ser Ser Asn Glu Ala Leu Ile
165 170 175
Gln Ala Leu Leu Glu Leu Leu Ser Ala Leu Val His Val Leu Ser Ser
180 185 190
Ala Ser Ile Gly Asn Val Ser Ser Val Gly Val Asp Ser Thr Leu Asn
195 200 205
Val Val Gln Asp Ser Val Gly Gln Tyr Val Gly
210 215
<210> 56
<211> 219
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 56
Gly Gly Gln Gly Gly Phe Ser Gly Gln Gly Gln Gly Gly Phe Gly Pro
1 5 10 15
Gly Ala Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
20 25 30
Arg Gln Gly Gly Gln Gly Gln Gly Gly Phe Gly Gln Gly Ala Gly Gly
35 40 45
Asn Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gln
50 55 60
Gln Gly Gly Gln Gly Gly Phe Ser Gly Arg Gly Gln Gly Gly Phe Gly
65 70 75 80
Pro Gly Ala Gly Ser Ser Ala Ala Ala Ala Ala Ala Gly Gln Gly Gly
85 90 95
Gln Gly Gln Gly Gly Phe Gly Gln Gly Ala Gly Gly Asn Ala Ala Ala
100 105 110
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gln Gly Gly
115 120 125
Gln Gly Arg Gly Gly Phe Gly Gln Gly Ala Gly Gly Asn Ala Ala Ala
130 135 140
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gln Gln Gly Gly
145 150 155 160
Gln Gly Gly Phe Gly Gly Arg Gly Gln Gly Gly Phe Gly Pro Gly Ala
165 170 175
Gly Ser Ser Ala Ala Ala Ala Ala Ala Gly Gln Gly Gly Gln Gly Arg
180 185 190
Gly Gly Phe Gly Gln Gly Ala Gly Gly Asn Ala Ala Ala Ala Ser Ala
195 200 205
Ala Ala Ala Ala Ser Ala Ala Ala Ala Gly Gln
210 215
<210> 57
<211> 218
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 57
Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Gly Ala Gly
1 5 10 15
Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Gly Ala Gly Gln Gln Gly
20 25 30
Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ala Ala Ala Ala Ala
35 40 45
Ala Val Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser
50 55 60
Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro
65 70 75 80
Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly
85 90 95
Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly
100 105 110
Gly Gln Gln Gly Pro Gly Gly Leu Gly Pro Tyr Gly Pro Ser Ala Ala
115 120 125
Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln
130 135 140
Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Arg Pro Gly
145 150 155 160
Gly Leu Gly Pro Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala
165 170 175
Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln Gly
180 185 190
Pro Gly Ser Gly Gly Gln Gln Arg Pro Gly Gly Leu Gly Pro Tyr Gly
195 200 205
Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala
210 215
<210> 58
<211> 217
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 58
Gly Ala Gly Ala Gly Gly Gly Tyr Gly Gly Gly Tyr Ser Ala Gly Gly
1 5 10 15
Gly Ala Gly Ala Gly Ser Gly Ala Ala Ala Gly Ala Gly Ala Gly Arg
20 25 30
Gly Gly Ala Gly Gly Tyr Ser Ala Gly Ala Gly Thr Gly Ala Gly Ala
35 40 45
Ala Ala Gly Ala Gly Thr Ala Gly Gly Tyr Ser Gly Gly Tyr Gly Ala
50 55 60
Gly Ala Ser Ser Ser Ala Gly Ser Ser Phe Ile Ser Ser Ser Ser Met
65 70 75 80
Ser Ser Ser Gln Ala Thr Gly Tyr Ser Ser Ser Ser Gly Tyr Gly Gly
85 90 95
Gly Ala Ala Ser Ala Ala Ala Gly Ala Gly Ala Ala Ala Gly Gly Tyr
100 105 110
Gly Gly Gly Tyr Gly Ala Gly Ala Gly Ala Gly Ala Ala Ala Ala Ser
115 120 125
Gly Ala Thr Gly Arg Val Ala Asn Ser Leu Gly Ala Met Ala Ser Gly
130 135 140
Gly Ile Asn Ala Leu Pro Gly Val Phe Ser Asn Ile Phe Ser Gln Val
145 150 155 160
Ser Ala Ala Ser Gly Gly Ala Ser Gly Gly Ala Val Leu Val Gln Ala
165 170 175
Leu Thr Glu Val Ile Ala Leu Leu Leu His Ile Leu Ser Ser Ala Ser
180 185 190
Ile Gly Asn Val Ser Ser Gln Gly Leu Glu Gly Ser Met Ala Ile Ala
195 200 205
Gln Gln Ala Ile Gly Ala Tyr Ala Gly
210 215
<210> 59
<211> 216
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 59
Gly Ala Gly Ala Gly Gly Ala Gly Gly Tyr Ala Gln Gly Tyr Gly Ala
1 5 10 15
Gly Ala Gly Ala Gly Ala Gly Ala Gly Thr Gly Ala Gly Gly Ala Gly
20 25 30
Gly Tyr Gly Gln Gly Tyr Gly Ala Gly Ser Gly Ala Gly Ala Gly Gly
35 40 45
Ala Gly Gly Tyr Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly Asp
50 55 60
Ala Ser Gly Tyr Gly Gln Gly Tyr Gly Asp Gly Ala Gly Ala Gly Ala
65 70 75 80
Gly Ala Ala Ala Ala Ala Gly Ala Ala Ala Gly Ala Arg Gly Ala Gly
85 90 95
Gly Tyr Gly Gly Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala
100 105 110
Ala Gly Gly Tyr Gly Gln Gly Tyr Gly Ala Gly Ala Gly Glu Gly Ala
115 120 125
Gly Ala Gly Ala Gly Ala Gly Ala Val Ala Gly Ala Gly Ala Ala Ala
130 135 140
Ala Ala Gly Ala Gly Ala Gly Ala Gly Gly Ala Glu Gly Tyr Gly Ala
145 150 155 160
Gly Ala Gly Ala Gly Gly Ala Gly Gly Tyr Gly Gln Ser Tyr Gly Asp
165 170 175
Gly Ala Ala Ala Ala Ala Gly Ser Gly Ala Gly Ala Gly Gly Ser Gly
180 185 190
Gly Tyr Gly Ala Gly Ala Gly Ala Gly Ser Gly Ala Gly Ala Ala Gly
195 200 205
Gly Tyr Gly Gly Gly Ala Gly Ala
210 215
<210> 60
<211> 216
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 60
Gly Pro Gly Gly Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gly Tyr Gly
1 5 10 15
Pro Gly Gln Gln Gly Pro Gly Arg Tyr Gly Pro Gly Gln Gln Gly Pro
20 25 30
Ser Gly Pro Gly Ser Ala Ala Ala Ala Ala Ala Gly Ser Gly Gln Gln
35 40 45
Gly Pro Gly Gly Tyr Gly Pro Arg Gln Gln Gly Pro Gly Gly Tyr Gly
50 55 60
Gln Gly Gln Gln Gly Pro Ser Gly Pro Gly Ser Ala Ala Ala Ala Ser
65 70 75 80
Ala Ala Ala Ser Ala Glu Ser Gly Gln Gln Gly Pro Gly Gly Tyr Gly
85 90 95
Pro Gly Gln Gln Gly Pro Gly Gly Tyr Gly Pro Gly Gln Gln Gly Pro
100 105 110
Gly Gly Tyr Gly Pro Gly Gln Gln Gly Pro Ser Gly Pro Gly Ser Ala
115 120 125
Ala Ala Ala Ala Ala Ala Ala Ser Gly Pro Gly Gln Gln Gly Pro Gly
130 135 140
Gly Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gly Tyr Gly Pro Gly Gln
145 150 155 160
Gln Gly Pro Ser Gly Pro Gly Ser Ala Ala Ala Ala Ala Ala Ala Ala
165 170 175
Ser Gly Pro Gly Gln Gln Gly Pro Gly Gly Tyr Gly Pro Gly Gln Gln
180 185 190
Gly Pro Gly Gly Tyr Gly Pro Gly Gln Gln Gly Leu Ser Gly Pro Gly
195 200 205
Ser Ala Ala Ala Ala Ala Ala Ala
210 215
<210> 61
<211> 216
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 61
Gly Arg Gly Pro Gly Gly Tyr Gly Gln Gly Gln Gln Gly Pro Gly Gly
1 5 10 15
Pro Gly Ala Ala Ala Ala Ala Ala Gly Pro Gly Gly Tyr Gly Pro Gly
20 25 30
Gln Gln Gly Pro Gly Ala Ala Ala Ala Ala Ala Ala Gly Ser Gly Pro
35 40 45
Gly Gly Tyr Gly Pro Gly Gln Gln Gly Pro Gly Arg Ser Gly Ala Ala
50 55 60
Ala Ala Ala Ala Ala Ala Gly Arg Gly Pro Gly Gly Tyr Gly Pro Gly
65 70 75 80
Gln Gln Gly Pro Gly Gly Pro Gly Ala Ala Ala Ala Ala Ala Gly Pro
85 90 95
Gly Gly Tyr Gly Pro Gly Gln Gln Gly Pro Gly Ala Ala Ala Ala Ala
100 105 110
Ser Ala Gly Arg Gly Pro Gly Gly Tyr Gly Pro Gly Gln Gln Gly Pro
115 120 125
Gly Gly Ser Gly Ala Ala Ala Ala Ala Ala Gly Arg Gly Pro Gly Gly
130 135 140
Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gly Pro Gly Ala Ala Ala Ala
145 150 155 160
Ala Ala Ala Gly Arg Gly Pro Gly Gly Tyr Gly Pro Gly Gln Gln Gly
165 170 175
Pro Gly Gln Gln Gly Pro Gly Gly Ser Gly Ala Ala Ala Ala Ala Ala
180 185 190
Gly Arg Gly Pro Gly Gly Tyr Gly Pro Gly Gln Gln Gly Pro Gly Gly
195 200 205
Pro Gly Ala Ala Ala Ala Ala Ala
210 215
<210> 62
<211> 214
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 62
Gly Val Gly Ala Gly Gly Glu Gly Gly Tyr Asp Gln Gly Tyr Gly Ala
1 5 10 15
Gly Ala Gly Ala Gly Ser Gly Gly Gly Ala Gly Gly Ala Gly Gly Tyr
20 25 30
Gly Gly Gly Ala Gly Ala Gly Ser Gly Gly Gly Ala Gly Gly Ala Gly
35 40 45
Gly Tyr Gly Gly Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly Gly
50 55 60
Ala Gly Gly Tyr Gly Gly Gly Ala Gly Ala Gly Thr Gly Ala Arg Ala
65 70 75 80
Gly Ala Gly Gly Val Gly Gly Tyr Gly Gln Ser Tyr Gly Ala Gly Ala
85 90 95
Ser Ala Ala Ala Gly Ala Gly Val Gly Ala Gly Gly Ala Gly Ala Gly
100 105 110
Gly Ala Gly Gly Tyr Gly Gln Gly Tyr Gly Ala Gly Ala Gly Ile Gly
115 120 125
Ala Gly Asp Ala Gly Gly Tyr Gly Gly Gly Ala Gly Ala Gly Ala Ser
130 135 140
Ala Gly Ala Gly Gly Tyr Gly Gly Gly Ala Gly Ala Gly Ala Gly Gly
145 150 155 160
Val Gly Gly Tyr Gly Lys Gly Tyr Gly Ala Gly Ser Gly Ala Gly Ala
165 170 175
Ala Ala Ala Ala Gly Ala Gly Ala Gly Ser Ala Gly Gly Tyr Gly Arg
180 185 190
Gly Asp Gly Ala Gly Ala Gly Gly Ala Ser Gly Tyr Gly Gln Gly Tyr
195 200 205
Gly Ala Gly Ala Ala Ala
210
<210> 63
<211> 212
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 63
Gly Tyr Gly Ala Gly Ala Gly Arg Gly Tyr Gly Ala Gly Ala Gly Ala
1 5 10 15
Gly Ala Gly Ala Val Ala Ala Ser Gly Ala Gly Ala Gly Ala Gly Tyr
20 25 30
Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly Tyr Gly Ala Gly Ala
35 40 45
Gly Arg Gly Tyr Gly Ala Gly Ala Gly Ala Gly Ala Gly Ser Gly Ala
50 55 60
Ala Ser Gly Ala Gly Ala Gly Ala Gly Tyr Gly Ala Gly Ala Gly Ala
65 70 75 80
Gly Ala Gly Tyr Gly Ala Gly Ala Gly Ser Gly Tyr Gly Thr Gly Ala
85 90 95
Gly Ala Gly Ala Gly Ala Ala Ala Ala Gly Gly Ala Gly Ala Gly Ala
100 105 110
Gly Tyr Gly Ala Gly Ala Gly Arg Gly Tyr Gly Ala Gly Ala Gly Ala
115 120 125
Gly Ala Ala Ser Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Ala Ser
130 135 140
Gly Ala Gly Ala Gly Ser Gly Tyr Gly Ala Gly Ala Ala Ala Ala Gly
145 150 155 160
Gly Ala Gly Ala Gly Ala Gly Gly Gly Tyr Gly Ala Gly Ala Gly Arg
165 170 175
Gly Tyr Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly Ser Gly Ser
180 185 190
Gly Ser Ala Ala Gly Tyr Gly Gln Gly Tyr Gly Ser Gly Ser Gly Ala
195 200 205
Gly Ala Ala Ala
210
<210> 64
<211> 198
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 64
Gly Gln Gly Thr Asp Ser Ser Ala Ser Ser Val Ser Thr Ser Thr Ser
1 5 10 15
Val Ser Ser Ser Ala Thr Gly Pro Asp Thr Gly Tyr Pro Val Gly Tyr
20 25 30
Tyr Gly Ala Gly Gln Ala Glu Ala Ala Ala Ser Ala Ala Ala Ala Ala
35 40 45
Ala Ala Ser Ala Ala Glu Ala Ala Thr Ile Ala Gly Leu Gly Tyr Gly
50 55 60
Arg Gln Gly Gln Gly Thr Asp Ser Ser Ala Ser Ser Val Ser Thr Ser
65 70 75 80
Thr Ser Val Ser Ser Ser Ala Thr Gly Pro Asp Met Gly Tyr Pro Val
85 90 95
Gly Asn Tyr Gly Ala Gly Gln Ala Glu Ala Ala Ala Ser Ala Ala Ala
100 105 110
Ala Ala Ala Ala Ser Ala Ala Glu Ala Ala Thr Ile Ala Ser Leu Gly
115 120 125
Tyr Gly Arg Gln Gly Gln Gly Thr Asp Ser Ser Ala Ser Ser Val Ser
130 135 140
Thr Ser Thr Ser Val Ser Ser Ser Ala Thr Gly Pro Gly Ser Arg Tyr
145 150 155 160
Pro Val Arg Asp Tyr Gly Ala Asp Gln Ala Glu Ala Ala Ala Ser Ala
165 170 175
Ala Ala Ala Ala Ala Ala Ala Ala Ser Ala Ala Glu Glu Ile Ala Ser
180 185 190
Leu Gly Tyr Gly Arg Gln
195
<210> 65
<211> 198
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 65
Gly Gln Gly Thr Asp Ser Val Ala Ser Ser Ala Ser Ser Ser Ala Ser
1 5 10 15
Ala Ser Ser Ser Ala Thr Gly Pro Asp Thr Gly Tyr Pro Val Gly Tyr
20 25 30
Tyr Gly Ala Gly Gln Ala Glu Ala Ala Ala Ser Ala Ala Ala Ala Ala
35 40 45
Ala Ala Ser Ala Ala Glu Ala Ala Thr Ile Ala Gly Leu Gly Tyr Gly
50 55 60
Arg Gln Gly Gln Gly Thr Asp Ser Ser Ala Ser Ser Val Ser Thr Ser
65 70 75 80
Thr Ser Val Ser Ser Ser Ala Thr Gly Pro Gly Ser Arg Tyr Pro Val
85 90 95
Arg Asp Tyr Gly Ala Asp Gln Ala Glu Ala Ala Ala Ser Ala Thr Ala
100 105 110
Ala Ala Ala Ala Ala Ala Ser Ala Ala Glu Glu Ile Ala Ser Leu Gly
115 120 125
Tyr Gly Arg Gln Gly Gln Gly Thr Asp Ser Val Ala Ser Ser Ala Ser
130 135 140
Ser Ser Ala Ser Ala Ser Ser Ser Ala Thr Gly Pro Asp Thr Gly Tyr
145 150 155 160
Pro Val Gly Tyr Tyr Gly Ala Gly Gln Ala Glu Ala Ala Ala Ser Ala
165 170 175
Ala Ala Ala Ala Ala Ala Ser Ala Ala Glu Ala Ala Thr Ile Ala Gly
180 185 190
Leu Gly Tyr Gly Arg Gln
195
<210> 66
<211> 195
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 66
Gly Gln Gly Gly Gln Gly Gly Tyr Gly Gly Leu Gly Gln Gly Gly Tyr
1 5 10 15
Gly Gln Gly Ala Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala
20 25 30
Ala Ala Ala Ala Gly Gly Gln Gly Gly Gln Gly Gln Gly Arg Tyr Gly
35 40 45
Gln Gly Ala Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
50 55 60
Ala Ala Ala Ala Gly Arg Gly Gln Gly Gly Tyr Gly Gln Gly Ser Gly
65 70 75 80
Gly Asn Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly
85 90 95
Gln Gly Ser Gln Gly Gly Gln Gly Gly Gln Gly Gln Gly Gly Tyr Gly
100 105 110
Gln Gly Ala Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
115 120 125
Ala Ala Ala Ser Gly Arg Gly Gln Gly Gly Tyr Gly Gln Gly Ala Gly
130 135 140
Gly Asn Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
145 150 155 160
Gly Gln Gly Gly Gln Gly Gly Tyr Gly Gly Leu Gly Gln Gly Gly Tyr
165 170 175
Gly Gln Gly Ala Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala
180 185 190
Ala Ala Ala
195
<210> 67
<211> 193
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 67
Gly Gly Leu Gly Gly Gln Gly Gly Leu Gly Gly Leu Gly Ser Gln Gly
1 5 10 15
Ala Gly Leu Gly Gly Tyr Gly Gln Gly Gly Ala Gly Gln Gly Gly Ala
20 25 30
Ala Ala Ala Ala Ala Ala Ala Gly Gly Leu Gly Gly Gln Gly Gly Arg
35 40 45
Gly Gly Leu Gly Ser Gln Gly Ala Gly Gln Gly Gly Tyr Gly Gln Gly
50 55 60
Gly Ala Gly Gln Gly Gly Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly
65 70 75 80
Leu Gly Gly Gln Gly Gly Leu Gly Ala Leu Gly Ser Gln Gly Ala Gly
85 90 95
Gln Gly Gly Ala Gly Gln Gly Gly Tyr Gly Gln Gly Gly Ala Ala Ala
100 105 110
Ala Ala Ala Gly Gly Leu Gly Gly Gln Gly Gly Leu Gly Gly Leu Gly
115 120 125
Ser Gln Gly Ala Gly Gln Gly Gly Tyr Gly Gln Gly Gly Ala Gly Gln
130 135 140
Gly Gly Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Leu Gly Gly Gln
145 150 155 160
Gly Gly Leu Gly Gly Leu Gly Ser Gln Gly Ala Gly Pro Gly Gly Tyr
165 170 175
Gly Gln Gly Gly Ala Gly Gln Gly Gly Ala Ala Ala Ala Ala Ala Ala
180 185 190
Ala
<210> 68
<211> 192
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 68
Gly Gly Gln Gly Arg Gly Gly Phe Gly Gln Gly Ala Gly Gly Asn Ala
1 5 10 15
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gln Gln Val
20 25 30
Gly Gln Phe Gly Phe Gly Gly Arg Gly Gln Gly Gly Phe Gly Pro Phe
35 40 45
Ala Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ser Ala Ala Ala Gly
50 55 60
Gln Gly Gly Gln Gly Gln Gly Gly Phe Gly Gln Gly Ala Gly Gly Asn
65 70 75 80
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Arg Gln Gly Gly
85 90 95
Gln Gly Gln Gly Gly Phe Ser Gln Gly Ala Gly Gly Asn Ala Ala Ala
100 105 110
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gln Gln Gly Gly
115 120 125
Gln Gly Gly Phe Gly Gly Arg Gly Gln Gly Gly Phe Gly Pro Gly Ala
130 135 140
Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Thr Ala Ala Ala Gly Gln
145 150 155 160
Gly Gly Gln Gly Arg Gly Gly Phe Gly Gln Gly Ala Gly Ser Asn Ala
165 170 175
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gln
180 185 190
<210> 69
<211> 190
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 69
Gly Gly Gln Gly Gly Gln Gly Gly Tyr Gly Gly Leu Gly Ser Gln Gly
1 5 10 15
Ala Gly Gln Gly Gly Tyr Gly Ala Gly Gln Gly Ala Ala Ala Ala Ala
20 25 30
Ala Ala Ala Gly Gly Ala Gly Gly Ala Gly Arg Gly Gly Leu Gly Ala
35 40 45
Gly Gly Ala Gly Gln Gly Tyr Gly Ala Gly Leu Gly Gly Gln Gly Gly
50 55 60
Ala Gly Gln Ala Ala Ala Ala Ala Ala Ala Gly Gly Ala Gly Gly Ala
65 70 75 80
Arg Gln Gly Gly Leu Gly Ala Gly Gly Ala Gly Gln Gly Tyr Gly Ala
85 90 95
Gly Leu Gly Gly Gln Gly Gly Ala Gly Gln Gly Gly Ala Ala Ala Ala
100 105 110
Ala Ala Ala Ala Gly Gly Gln Gly Gly Gln Gly Gly Tyr Gly Gly Leu
115 120 125
Gly Ser Gln Gly Ala Gly Gln Gly Gly Tyr Gly Ala Gly Gln Gly Gly
130 135 140
Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Gln Gly Gly Gln Gly Gly
145 150 155 160
Tyr Gly Gly Leu Gly Ser Gln Gly Ala Gly Gln Gly Gly Tyr Gly Gly
165 170 175
Arg Gln Gly Gly Ala Gly Ala Ala Ala Ala Ala Ala Ala Ala
180 185 190
<210> 70
<211> 188
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 70
Gly Gly Ala Gly Gln Arg Gly Tyr Gly Gly Leu Gly Asn Gln Gly Ala
1 5 10 15
Gly Arg Gly Gly Leu Gly Gly Gln Gly Ala Gly Ala Ala Ala Ala Ala
20 25 30
Ala Ala Gly Gly Ala Gly Gln Gly Gly Tyr Gly Gly Leu Gly Asn Gln
35 40 45
Gly Ala Gly Arg Gly Gly Gln Gly Ala Ala Ala Ala Ala Gly Gly Ala
50 55 60
Gly Gln Gly Gly Tyr Gly Gly Leu Gly Ser Gln Gly Ala Gly Arg Gly
65 70 75 80
Gly Gln Gly Ala Gly Ala Ala Ala Ala Ala Ala Val Gly Ala Gly Gln
85 90 95
Glu Gly Ile Arg Gly Gln Gly Ala Gly Gln Gly Gly Tyr Gly Gly Leu
100 105 110
Gly Ser Gln Gly Ser Gly Arg Gly Gly Leu Gly Gly Gln Gly Ala Gly
115 120 125
Ala Ala Ala Ala Ala Ala Gly Gly Ala Gly Gln Gly Gly Leu Gly Gly
130 135 140
Gln Gly Ala Gly Gln Gly Ala Gly Ala Ala Ala Ala Ala Ala Gly Gly
145 150 155 160
Val Arg Gln Gly Gly Tyr Gly Gly Leu Gly Ser Gln Gly Ala Gly Arg
165 170 175
Gly Gly Gln Gly Ala Gly Ala Ala Ala Ala Ala Ala
180 185
<210> 71
<211> 186
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 71
Gly Gly Ala Gly Gln Gly Gly Leu Gly Gly Gln Gly Ala Gly Gln Gly
1 5 10 15
Ala Gly Ala Ser Ala Ala Ala Ala Gly Gly Ala Gly Gln Gly Gly Tyr
20 25 30
Gly Gly Leu Gly Ser Gln Gly Ala Gly Arg Gly Gly Glu Gly Ala Gly
35 40 45
Ala Ala Ala Ala Ala Ala Gly Gly Ala Gly Gln Gly Gly Tyr Gly Gly
50 55 60
Leu Gly Gly Gln Gly Ala Gly Gln Gly Gly Tyr Gly Gly Leu Gly Ser
65 70 75 80
Gln Gly Ala Gly Arg Gly Gly Leu Gly Gly Gln Gly Ala Gly Ala Ala
85 90 95
Ala Ala Gly Gly Ala Gly Gln Gly Gly Leu Gly Gly Gln Gly Ala Gly
100 105 110
Gln Gly Ala Gly Ala Ala Ala Ala Ala Ala Gly Gly Ala Gly Gln Gly
115 120 125
Gly Tyr Gly Gly Leu Gly Ser Gln Gly Ala Gly Arg Gly Gly Leu Gly
130 135 140
Gly Gln Gly Ala Gly Ala Val Ala Ala Ala Ala Ala Gly Gly Ala Gly
145 150 155 160
Gln Gly Gly Tyr Gly Gly Leu Gly Ser Gln Gly Ala Gly Arg Gly Gly
165 170 175
Gln Gly Ala Gly Ala Ala Ala Ala Ala Ala
180 185
<210> 72
<211> 182
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 72
Gly Ala Gly Ala Gly Ala Gly Ala Gly Ser Gly Ala Gly Ala Ala Gly
1 5 10 15
Gly Tyr Gly Gly Gly Ala Gly Ala Gly Val Gly Ala Gly Gly Ala Gly
20 25 30
Gly Tyr Asp Gln Gly Tyr Gly Ala Gly Ala Gly Ala Gly Ser Gly Ala
35 40 45
Gly Ala Gly Gly Ala Gly Gly Tyr Gly Gly Gly Ala Gly Ala Gly Ala
50 55 60
Asp Ala Gly Ala Gly Gly Ala Gly Gly Tyr Gly Gly Gly Ala Gly Ala
65 70 75 80
Gly Ala Gly Ala Arg Ala Gly Ala Gly Gly Val Gly Gly Tyr Gly Gln
85 90 95
Ser Tyr Gly Ala Gly Ala Gly Ala Gly Ala Gly Val Gly Ala Gly Gly
100 105 110
Ala Gly Ala Gly Gly Ala Asp Gly Tyr Gly Gln Gly Tyr Gly Ala Gly
115 120 125
Ala Gly Thr Gly Ala Gly Asp Ala Gly Gly Tyr Gly Gly Gly Ala Gly
130 135 140
Ala Gly Ala Ser Ala Gly Ala Gly Gly Tyr Gly Gly Gly Ala Gly Ala
145 150 155 160
Gly Gly Val Gly Val Tyr Gly Lys Gly Tyr Gly Ser Gly Ser Gly Ala
165 170 175
Gly Ala Ala Ala Ala Ala
180
<210> 73
<211> 182
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 73
Gly Gly Ala Gly Gly Tyr Gly Val Gly Gln Gly Tyr Gly Ala Gly Ala
1 5 10 15
Gly Ala Gly Ala Ala Ala Gly Ala Gly Ala Gly Gly Ala Gly Gly Tyr
20 25 30
Gly Ala Gly Gln Gly Tyr Gly Ala Gly Ala Gly Val Gly Ala Ala Ala
35 40 45
Ala Ala Gly Ala Gly Ala Gly Val Gly Gly Ala Gly Gly Tyr Gly Arg
50 55 60
Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Ala Ala Gly Ala
65 70 75 80
Gly Ala Gly Ala Ala Ala Gly Ala Gly Ala Gly Gly Ala Gly Gly Tyr
85 90 95
Gly Ala Gly Gln Gly Tyr Gly Ala Gly Ala Gly Val Gly Ala Ala Ala
100 105 110
Ala Ala Gly Ala Gly Ala Gly Val Gly Gly Ala Gly Gly Tyr Gly Arg
115 120 125
Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly Gly Ala Gly Gly Tyr
130 135 140
Gly Arg Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly Gly
145 150 155 160
Ala Gly Gly Tyr Gly Ala Gly Gln Gly Tyr Gly Ala Gly Ala Gly Ala
165 170 175
Gly Ala Ala Ala Ala Ala
180
<210> 74
<211> 182
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 74
Gly Glu Ala Phe Ser Ala Ser Ser Ala Ser Ser Ala Val Val Phe Glu
1 5 10 15
Ser Ala Gly Pro Gly Glu Glu Ala Gly Ser Ser Gly Asp Gly Ala Ser
20 25 30
Ala Ala Ala Ser Ala Ala Ala Ala Ala Gly Ala Gly Ser Gly Arg Arg
35 40 45
Gly Pro Gly Gly Ala Arg Ser Arg Gly Gly Ala Gly Ala Gly Ala Gly
50 55 60
Ala Gly Ser Gly Val Gly Gly Tyr Gly Ser Gly Ser Gly Ala Gly Ala
65 70 75 80
Gly Ala Gly Ala Gly Ala Gly Ala Gly Gly Glu Gly Gly Phe Gly Glu
85 90 95
Gly Gln Gly Tyr Gly Ala Gly Ala Gly Ala Gly Phe Gly Ser Gly Ala
100 105 110
Gly Ala Gly Ala Gly Ala Gly Ser Gly Ala Gly Ala Gly Glu Gly Val
115 120 125
Gly Ser Gly Ala Gly Ala Gly Ala Gly Ala Gly Phe Gly Val Gly Ala
130 135 140
Gly Ala Gly Ala Gly Ala Gly Ala Gly Phe Gly Ser Gly Ala Gly Ala
145 150 155 160
Gly Ser Gly Ala Gly Ala Gly Tyr Gly Ala Gly Arg Ala Gly Gly Arg
165 170 175
Gly Arg Gly Gly Arg Gly
180
<210> 75
<211> 182
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 75
Gly Glu Ala Phe Ser Ala Ser Ser Ala Ser Ser Ala Val Val Phe Glu
1 5 10 15
Ser Ala Gly Pro Gly Glu Glu Ala Gly Ser Ser Gly Gly Gly Ala Ser
20 25 30
Ala Ala Ala Ser Ala Ala Ala Ala Ala Gly Ala Gly Ser Gly Arg Arg
35 40 45
Gly Pro Gly Gly Ala Arg Ser Arg Gly Gly Ala Gly Ala Gly Ala Gly
50 55 60
Ala Gly Ser Gly Val Gly Gly Tyr Gly Ser Gly Ser Gly Ala Gly Ala
65 70 75 80
Gly Ala Gly Ala Gly Ala Gly Ala Gly Gly Glu Gly Gly Phe Gly Glu
85 90 95
Gly Gln Gly Tyr Gly Ala Gly Ala Gly Ala Gly Phe Gly Ser Gly Ala
100 105 110
Gly Ala Gly Ala Gly Ala Gly Ser Gly Ala Gly Ala Gly Glu Gly Val
115 120 125
Gly Ser Gly Ala Gly Ala Gly Ala Gly Ala Gly Phe Gly Val Gly Ala
130 135 140
Gly Ala Gly Ala Gly Ala Gly Ala Gly Phe Gly Ser Gly Ala Gly Ala
145 150 155 160
Gly Ser Gly Ala Gly Ala Gly Tyr Gly Ala Gly Arg Ala Gly Gly Arg
165 170 175
Gly Arg Gly Gly Arg Gly
180
<210> 76
<211> 182
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 76
Gly Asn Gly Leu Gly Gln Ala Leu Leu Ala Asn Gly Val Leu Asn Ser
1 5 10 15
Gly Asn Tyr Leu Gln Leu Ala Asn Ser Leu Ala Tyr Ser Phe Gly Ser
20 25 30
Ser Leu Ser Gln Tyr Ser Ser Ser Ala Ala Gly Ala Ser Ala Ala Gly
35 40 45
Ala Ala Ser Gly Ala Ala Gly Ala Gly Ala Gly Ala Ala Ser Ser Gly
50 55 60
Gly Ser Ser Gly Ser Ala Ser Ser Ser Thr Thr Thr Thr Thr Thr Thr
65 70 75 80
Ser Thr Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser
85 90 95
Ala Ala Ala Ser Thr Ser Ala Ser Ala Ser Ala Ser Ala Ser Ala Ser
100 105 110
Ala Ser Ala Phe Ser Gln Thr Phe Val Gln Thr Val Leu Gln Ser Ala
115 120 125
Ala Phe Gly Ser Tyr Phe Gly Gly Asn Leu Ser Leu Gln Ser Ala Gln
130 135 140
Ala Ala Ala Ser Ala Ala Ala Gln Ala Ala Ala Gln Gln Ile Gly Leu
145 150 155 160
Gly Ser Tyr Gly Tyr Ala Leu Ala Asn Ala Val Ala Ser Ala Phe Ala
165 170 175
Ser Ala Gly Ala Asn Ala
180
<210> 77
<211> 182
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 77
Gly Asn Gly Leu Gly Gln Ala Leu Leu Ala Asn Gly Val Leu Asn Ser
1 5 10 15
Gly Asn Tyr Leu Gln Leu Ala Asn Ser Leu Ala Tyr Ser Phe Gly Ser
20 25 30
Ser Leu Ser Gln Tyr Ser Ser Ser Ala Ala Gly Ala Ser Ala Ala Gly
35 40 45
Ala Ala Ser Gly Ala Ala Gly Ala Gly Ala Gly Ala Ala Ser Ser Gly
50 55 60
Gly Ser Ser Gly Ser Ala Ser Ser Ser Thr Thr Thr Thr Thr Thr Thr
65 70 75 80
Ser Thr Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser
85 90 95
Ala Ala Ala Ser Thr Ser Ala Ser Ala Ser Ala Ser Ala Ser Ala Ser
100 105 110
Ala Ser Ala Phe Ser Gln Thr Phe Val Gln Thr Val Leu Gln Ser Ala
115 120 125
Ala Phe Gly Ser Tyr Phe Gly Gly Asn Leu Ser Leu Gln Ser Ala Gln
130 135 140
Ala Ala Ala Ser Ala Ala Ala Gln Ala Ala Ala Gln Gln Ile Gly Leu
145 150 155 160
Gly Ser Tyr Gly Tyr Ala Leu Ala Asn Ala Val Ala Ser Ala Phe Ala
165 170 175
Ser Ala Gly Ala Asn Ala
180
<210> 78
<211> 182
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 78
Gly Asn Gly Leu Gly Gln Ala Leu Leu Ala Asn Gly Val Leu Asn Ser
1 5 10 15
Gly Asn Tyr Leu Gln Leu Ala Asn Ser Leu Ala Tyr Ser Phe Gly Ser
20 25 30
Ser Leu Ser Gln Tyr Ser Ser Ser Ala Ala Gly Ala Ser Ala Ala Gly
35 40 45
Ala Ala Ser Gly Ala Ala Gly Ala Gly Ala Gly Ala Ala Ser Ser Gly
50 55 60
Gly Ser Ser Gly Ser Ala Ser Ser Ser Thr Thr Thr Thr Thr Thr Thr
65 70 75 80
Ser Thr Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser
85 90 95
Ala Ala Ala Ser Thr Ser Ala Ser Ala Ser Ala Ser Ala Ser Ala Ser
100 105 110
Ala Ser Ala Phe Ser Gln Thr Phe Val Gln Thr Val Leu Gln Ser Ala
115 120 125
Ala Phe Gly Ser Tyr Phe Gly Gly Asn Leu Ser Leu Gln Ser Ala Gln
130 135 140
Ala Ala Ala Ser Ala Ala Ala Gln Ala Ala Ala Gln Gln Ile Gly Leu
145 150 155 160
Gly Ser Tyr Gly Tyr Ala Leu Ala Asn Ala Val Ala Ser Ala Phe Ala
165 170 175
Ser Ala Gly Ala Asn Ala
180
<210> 79
<211> 180
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 79
Gly Ala Ser Gly Ala Gly Gln Gly Gln Gly Tyr Gly Gln Gln Gly Gln
1 5 10 15
Gly Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
20 25 30
Ala Ala Ala Gln Gly Gln Gly Gln Gly Tyr Gly Gln Gln Gly Gln Gly
35 40 45
Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Ala Ser Gly Ala
50 55 60
Gly Gln Gly Gln Gly Tyr Gly Gln Gln Gly Gln Gly Ser Ala Ala Ala
65 70 75 80
Ala Ala Ala Ala Ala Ala Ala Gly Ala Ser Gly Ala Gly Gln Gly Gln
85 90 95
Gly Tyr Gly Gln Gln Gly Gln Gly Gly Ser Ser Ala Ala Ala Ala Ala
100 105 110
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gln Gly Gln Gly Tyr
115 120 125
Gly Gln Gln Gly Gln Gly Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala
130 135 140
Gly Ala Ser Gly Ala Gly Gln Gly Gln Gly Tyr Gly Gln Gln Gly Gln
145 150 155 160
Gly Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
165 170 175
Ala Ala Ala Ala
180
<210> 80
<211> 179
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 80
Gly Arg Gly Gln Gly Gly Tyr Gly Gln Gly Ser Gly Gly Asn Ala Ala
1 5 10 15
Ala Ala Ala Ala Ala Gly Gln Gly Gly Phe Gly Gly Gln Glu Gly Asn
20 25 30
Gly Gln Gly Ala Gly Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
35 40 45
Ala Ala Gly Gly Ser Gly Gln Gly Arg Tyr Gly Gly Arg Gly Gln Gly
50 55 60
Gly Tyr Gly Gln Gly Ala Gly Ala Ala Ala Ser Ala Ala Ala Ala Ala
65 70 75 80
Ala Ala Ala Ala Ala Gly Gln Gly Gly Phe Gly Gly Gln Glu Gly Asn
85 90 95
Gly Gln Gly Ala Gly Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
100 105 110
Ala Ala Gly Gly Ser Gly Gln Gly Gly Tyr Gly Gly Arg Gly Gln Gly
115 120 125
Gly Tyr Gly Gln Gly Ala Gly Ala Ala Ala Ala Ala Ala Ala Ala Ala
130 135 140
Ala Ala Ala Ala Ala Gly Gln Gly Gly Gln Gly Gly Phe Gly Ser Gln
145 150 155 160
Gly Gly Asn Gly Gln Gly Ala Gly Ser Ala Ala Ala Ala Ala Ala Ala
165 170 175
Ala Ala Ala
<210> 81
<211> 178
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 81
Gly Gln Asn Thr Pro Trp Ser Ser Thr Glu Leu Ala Asp Ala Phe Ile
1 5 10 15
Asn Ala Phe Met Asn Glu Ala Gly Arg Thr Gly Ala Phe Thr Ala Asp
20 25 30
Gln Leu Asp Asp Met Ser Thr Ile Gly Asp Thr Ile Lys Thr Ala Met
35 40 45
Asp Lys Met Ala Arg Ser Asn Lys Ser Ser Lys Gly Lys Leu Gln Ala
50 55 60
Leu Asn Met Ala Phe Ala Ser Ser Met Ala Glu Ile Ala Ala Val Glu
65 70 75 80
Gln Gly Gly Leu Ser Val Asp Ala Lys Thr Asn Ala Ile Ala Asp Ser
85 90 95
Leu Asn Ser Ala Phe Tyr Gln Thr Thr Gly Ala Ala Asn Pro Gln Phe
100 105 110
Val Asn Glu Ile Arg Ser Leu Ile Asn Met Phe Ala Gln Ser Ser Ala
115 120 125
Asn Glu Val Ser Tyr Gly Gly Gly Tyr Gly Gly Gln Ser Ala Gly Ala
130 135 140
Ala Ala Ser Ala Ala Ala Ala Gly Gly Gly Gly Gln Gly Gly Tyr Gly
145 150 155 160
Asn Leu Gly Gly Gln Gly Ala Gly Ala Ala Ala Ala Ala Ala Ala Ser
165 170 175
Ala Ala
<210> 82
<211> 178
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 82
Gly Gln Asn Thr Pro Trp Ser Ser Thr Glu Leu Ala Asp Ala Phe Ile
1 5 10 15
Asn Ala Phe Leu Asn Glu Ala Gly Arg Thr Gly Ala Phe Thr Ala Asp
20 25 30
Gln Leu Asp Asp Met Ser Thr Ile Gly Asp Thr Leu Lys Thr Ala Met
35 40 45
Asp Lys Met Ala Arg Ser Asn Lys Ser Ser Gln Ser Lys Leu Gln Ala
50 55 60
Leu Asn Met Ala Phe Ala Ser Ser Met Ala Glu Ile Ala Ala Val Glu
65 70 75 80
Gln Gly Gly Leu Ser Val Ala Glu Lys Thr Asn Ala Ile Ala Asp Ser
85 90 95
Leu Asn Ser Ala Phe Tyr Gln Thr Thr Gly Ala Val Asn Val Gln Phe
100 105 110
Val Asn Glu Ile Arg Ser Leu Ile Ser Met Phe Ala Gln Ala Ser Ala
115 120 125
Asn Glu Val Ser Tyr Gly Gly Gly Tyr Gly Gly Gly Gln Gly Gly Gln
130 135 140
Ser Ala Gly Ala Ala Ala Ala Ala Ala Ser Ala Gly Ala Gly Gln Gly
145 150 155 160
Gly Tyr Gly Gly Leu Gly Gly Gln Gly Ala Gly Ser Ala Ala Ala Ala
165 170 175
Ala Ala
<210> 83
<211> 177
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 83
Gly Gly Gln Gly Gly Gln Gly Gly Tyr Gly Gly Leu Gly Ser Gln Gly
1 5 10 15
Ala Gly Gln Gly Gly Tyr Gly Gln Gly Gly Ala Ala Ala Ala Ala Ala
20 25 30
Ser Ala Gly Gly Gln Gly Gly Gln Gly Gly Tyr Gly Gly Leu Gly Ser
35 40 45
Gln Gly Ala Gly Gln Gly Gly Tyr Gly Gly Gly Ala Phe Ser Gly Gln
50 55 60
Gln Gly Gly Ala Ala Ser Val Ala Thr Ala Ser Ala Ala Ala Ser Arg
65 70 75 80
Leu Ser Ser Pro Gly Ala Ala Ser Arg Val Ser Ser Ala Val Thr Ser
85 90 95
Leu Val Ser Ser Gly Gly Pro Thr Asn Ser Ala Ala Leu Ser Asn Thr
100 105 110
Ile Ser Asn Val Val Ser Gln Ile Ser Ser Ser Asn Pro Gly Leu Ser
115 120 125
Gly Cys Asp Val Leu Val Gln Ala Leu Leu Glu Ile Val Ser Ala Leu
130 135 140
Val His Ile Leu Gly Ser Ala Asn Ile Gly Gln Val Asn Ser Ser Gly
145 150 155 160
Val Gly Arg Ser Ala Ser Ile Val Gly Gln Ser Ile Asn Gln Ala Phe
165 170 175
Ser
<210> 84
<211> 177
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 84
Gly Gly Ala Gly Gln Gly Gly Tyr Gly Gly Leu Gly Gly Gln Gly Ala
1 5 10 15
Gly Ala Ala Ala Ala Ala Ala Gly Gly Ala Gly Gln Gly Gly Tyr Gly
20 25 30
Gly Gln Gly Ala Gly Gln Gly Ala Ala Ala Ala Ala Ala Ser Gly Ala
35 40 45
Gly Gln Gly Gly Tyr Glu Gly Pro Gly Ala Gly Gln Gly Ala Gly Ala
50 55 60
Ala Ala Ala Ala Ala Gly Gly Ala Gly Gln Gly Gly Tyr Gly Gly Leu
65 70 75 80
Gly Gly Gln Gly Ala Gly Gln Gly Ala Gly Ala Ala Ala Ala Ala Ala
85 90 95
Gly Gly Ala Gly Gln Gly Gly Tyr Gly Gly Leu Gly Gly Gln Gly Ala
100 105 110
Gly Gln Gly Ala Gly Ala Ala Ala Ala Ala Ala Gly Gly Ala Gly Gln
115 120 125
Gly Gly Tyr Gly Gly Gln Gly Ala Gly Gln Gly Ala Ala Ala Ala Ala
130 135 140
Ala Gly Gly Ala Gly Gln Gly Gly Tyr Gly Gly Leu Gly Ser Gly Gln
145 150 155 160
Gly Gly Tyr Gly Arg Gln Gly Ala Gly Ala Ala Ala Ala Ala Ala Ala
165 170 175
Ala
<210> 85
<211> 175
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 85
Gly Ala Ser Ser Ala Ala Ala Ala Ala Ala Ala Thr Ala Thr Ser Gly
1 5 10 15
Gly Ala Pro Gly Gly Tyr Gly Gly Tyr Gly Pro Gly Ile Gly Gly Ala
20 25 30
Phe Val Pro Ala Ser Thr Thr Gly Thr Gly Ser Gly Ser Gly Ser Gly
35 40 45
Ala Gly Ala Ala Gly Ser Gly Gly Leu Gly Gly Leu Gly Ser Ser Gly
50 55 60
Gly Ser Gly Gly Leu Gly Gly Gly Asn Gly Gly Ser Gly Ala Ser Ala
65 70 75 80
Ala Ala Ser Ala Ala Ala Ala Ser Ser Ser Pro Gly Ser Gly Gly Tyr
85 90 95
Gly Pro Gly Gln Gly Val Gly Ser Gly Ser Gly Ser Gly Ala Ala Gly
100 105 110
Gly Ser Gly Thr Gly Ser Gly Ala Gly Gly Pro Gly Ser Gly Gly Tyr
115 120 125
Gly Gly Pro Gln Phe Phe Ala Ser Ala Tyr Gly Gly Gln Gly Leu Leu
130 135 140
Gly Thr Ser Gly Tyr Gly Asn Gly Gln Gly Gly Ala Ser Gly Thr Gly
145 150 155 160
Ser Gly Gly Val Gly Gly Ser Gly Ser Gly Ala Gly Ser Asn Ser
165 170 175
<210> 86
<211> 174
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 86
Gly Gln Pro Ile Trp Thr Asn Pro Asn Ala Ala Met Thr Met Thr Asn
1 5 10 15
Asn Leu Val Gln Cys Ala Ser Arg Ser Gly Val Leu Thr Ala Asp Gln
20 25 30
Met Asp Asp Met Gly Met Met Ala Asp Ser Val Asn Ser Gln Met Gln
35 40 45
Lys Met Gly Pro Asn Pro Pro Gln His Arg Leu Arg Ala Met Asn Thr
50 55 60
Ala Met Ala Ala Glu Val Ala Glu Val Val Ala Thr Ser Pro Pro Gln
65 70 75 80
Ser Tyr Ser Ala Val Leu Asn Thr Ile Gly Ala Cys Leu Arg Glu Ser
85 90 95
Met Met Gln Ala Thr Gly Ser Val Asp Asn Ala Phe Thr Asn Glu Val
100 105 110
Met Gln Leu Val Lys Met Leu Ser Ala Asp Ser Ala Asn Glu Val Ser
115 120 125
Thr Ala Ser Ala Ser Gly Ala Ser Tyr Ala Thr Ser Thr Ser Ser Ala
130 135 140
Val Ser Ser Ser Gln Ala Thr Gly Tyr Ser Thr Ala Ala Gly Tyr Gly
145 150 155 160
Asn Ala Ala Gly Ala Gly Ala Gly Ala Ala Ala Ala Val Ser
165 170
<210> 87
<211> 174
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 87
Gly Gln Lys Ile Trp Thr Asn Pro Asp Ala Ala Met Ala Met Thr Asn
1 5 10 15
Asn Leu Val Gln Cys Ala Gly Arg Ser Gly Ala Leu Thr Ala Asp Gln
20 25 30
Met Asp Asp Leu Gly Met Val Ser Asp Ser Val Asn Ser Gln Val Arg
35 40 45
Lys Met Gly Ala Asn Ala Pro Pro His Lys Ile Lys Ala Met Ser Thr
50 55 60
Ala Val Ala Ala Gly Val Ala Glu Val Val Ala Ser Ser Pro Pro Gln
65 70 75 80
Ser Tyr Ser Ala Val Leu Asn Thr Ile Gly Gly Cys Leu Arg Glu Ser
85 90 95
Met Met Gln Val Thr Gly Ser Val Asp Asn Thr Phe Thr Thr Glu Met
100 105 110
Met Gln Met Val Asn Met Phe Ala Ala Asp Asn Ala Asn Glu Val Ser
115 120 125
Ala Ser Ala Ser Gly Ser Gly Ala Ser Tyr Ala Thr Gly Thr Ser Ser
130 135 140
Ala Val Ser Thr Ser Gln Ala Thr Gly Tyr Ser Thr Ala Gly Gly Tyr
145 150 155 160
Gly Thr Ala Ala Gly Ala Gly Ala Gly Ala Ala Ala Ala Ala
165 170
<210> 88
<211> 174
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 88
Gly Ser Gly Tyr Gly Ala Gly Ala Gly Ala Gly Ala Gly Ser Gly Tyr
1 5 10 15
Gly Ala Gly Ala Gly Ala Gly Ser Gly Tyr Gly Ala Gly Ala Gly Ala
20 25 30
Gly Ala Gly Ser Gly Tyr Val Ala Gly Ala Gly Ala Gly Ala Gly Ala
35 40 45
Gly Ser Gly Tyr Gly Ala Gly Ala Gly Ala Gly Ala Gly Ser Ser Tyr
50 55 60
Ser Ala Gly Ala Gly Ala Gly Ala Gly Ser Gly Tyr Gly Ala Gly Ser
65 70 75 80
Ser Ala Ser Ala Gly Ser Ala Val Ser Thr Gln Thr Val Ser Ser Ser
85 90 95
Ala Thr Thr Ser Ser Gln Ser Ala Ala Ala Ala Thr Gly Ala Ala Tyr
100 105 110
Gly Thr Arg Ala Ser Thr Gly Ser Gly Ala Ser Ala Gly Ala Ala Ala
115 120 125
Ser Gly Ala Gly Ala Gly Tyr Gly Gly Gln Ala Gly Tyr Gly Gln Gly
130 135 140
Gly Gly Ala Ala Ala Tyr Arg Ala Gly Ala Gly Ser Gln Ala Ala Tyr
145 150 155 160
Gly Gln Gly Ala Ser Gly Ser Ser Gly Ala Ala Ala Ala Ala
165 170
<210> 89
<211> 171
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 89
Gly Gly Gln Gly Gly Arg Gly Gly Phe Gly Gly Leu Ser Ser Gln Gly
1 5 10 15
Ala Gly Gly Ala Gly Gln Gly Gly Ser Gly Ala Ala Ala Ala Ala Ala
20 25 30
Ala Ala Gly Gly Asp Gly Gly Ser Gly Leu Gly Asp Tyr Gly Ala Gly
35 40 45
Arg Gly Tyr Gly Ala Gly Leu Gly Gly Ala Gly Gly Ala Gly Val Ala
50 55 60
Ser Ala Ala Ala Ser Ala Ala Ala Ser Arg Leu Ser Ser Pro Ser Ala
65 70 75 80
Ala Ser Arg Val Ser Ser Ala Val Thr Ser Leu Ile Ser Gly Gly Gly
85 90 95
Pro Thr Asn Pro Ala Ala Leu Ser Asn Thr Phe Ser Asn Val Val Tyr
100 105 110
Gln Ile Ser Val Ser Ser Pro Gly Leu Ser Gly Cys Asp Val Leu Ile
115 120 125
Gln Ala Leu Leu Glu Leu Val Ser Ala Leu Val His Ile Leu Gly Ser
130 135 140
Ala Ile Ile Gly Gln Val Asn Ser Ser Ala Ala Gly Glu Ser Ala Ser
145 150 155 160
Leu Val Gly Gln Ser Val Tyr Gln Ala Phe Ser
165 170
<210> 90
<211> 169
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 90
Gly Val Gly Gln Ala Ala Thr Pro Trp Glu Asn Ser Gln Leu Ala Glu
1 5 10 15
Asp Phe Ile Asn Ser Phe Leu Arg Phe Ile Ala Gln Ser Gly Ala Phe
20 25 30
Ser Pro Asn Gln Leu Asp Asp Met Ser Ser Ile Gly Asp Thr Leu Lys
35 40 45
Thr Ala Ile Glu Lys Met Ala Gln Ser Arg Lys Ser Ser Lys Ser Lys
50 55 60
Leu Gln Ala Leu Asn Met Ala Phe Ala Ser Ser Met Ala Glu Ile Ala
65 70 75 80
Val Ala Glu Gln Gly Gly Leu Ser Leu Glu Ala Lys Thr Asn Ala Ile
85 90 95
Ala Asn Ala Leu Ala Ser Ala Phe Leu Glu Thr Thr Gly Phe Val Asn
100 105 110
Gln Gln Phe Val Ser Glu Ile Lys Ser Leu Ile Tyr Met Ile Ala Gln
115 120 125
Ala Ser Ser Asn Glu Ile Ser Gly Ser Ala Ala Ala Ala Gly Gly Gly
130 135 140
Ser Gly Gly Gly Gly Gly Ser Gly Gln Gly Gly Tyr Gly Gln Gly Ala
145 150 155 160
Ser Ala Ser Ala Ser Ala Ala Ala Ala
165
<210> 91
<211> 169
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 91
Gly Gly Gly Asp Gly Tyr Gly Gln Gly Gly Tyr Gly Asn Gln Arg Gly
1 5 10 15
Val Gly Ser Tyr Gly Gln Gly Ala Gly Ala Gly Ala Ala Ala Thr Ser
20 25 30
Ala Ala Gly Gly Ala Gly Ser Gly Arg Gly Gly Tyr Gly Glu Gln Gly
35 40 45
Gly Leu Gly Gly Tyr Gly Gln Gly Ala Gly Ala Gly Ala Ala Ser Thr
50 55 60
Ala Ala Gly Gly Gly Asp Gly Tyr Gly Gln Gly Gly Tyr Gly Asn Gln
65 70 75 80
Gly Gly Arg Gly Ser Tyr Gly Gln Gly Ser Gly Ala Gly Ala Gly Ala
85 90 95
Ala Val Ala Ala Ala Ala Gly Gly Ala Val Ser Gly Gln Gly Gly Tyr
100 105 110
Asp Gly Glu Gly Gly Gln Gly Gly Tyr Gly Gln Gly Ser Gly Ala Gly
115 120 125
Ala Ala Val Ala Ala Ala Ser Gly Gly Thr Gly Ala Gly Gln Gly Gly
130 135 140
Tyr Gly Ser Gln Gly Ser Gln Ala Gly Tyr Gly Gln Gly Ala Gly Phe
145 150 155 160
Arg Ala Ala Ala Ala Thr Ala Ala Ala
165
<210> 92
<211> 168
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 92
Gly Ala Gly Ala Gly Tyr Gly Gly Gln Val Gly Tyr Gly Gln Gly Ala
1 5 10 15
Gly Ala Ser Ala Gly Ala Ala Ala Ala Gly Ala Gly Ala Gly Tyr Gly
20 25 30
Gly Gln Ala Gly Tyr Gly Gln Gly Ala Gly Gly Ser Ala Gly Ala Ala
35 40 45
Ala Ala Gly Ala Gly Ala Gly Arg Gln Ala Gly Tyr Gly Gln Gly Ala
50 55 60
Gly Ala Ser Ala Arg Ala Ala Ala Ala Gly Ala Gly Thr Gly Tyr Gly
65 70 75 80
Gln Gly Ala Gly Ala Ser Ala Gly Ala Ala Ala Ala Gly Ala Gly Ala
85 90 95
Gly Ser Gln Val Gly Tyr Gly Gln Gly Ala Gly Ala Ser Ser Gly Ala
100 105 110
Ala Ala Ala Ala Gly Ala Gly Ala Gly Tyr Gly Gly Gln Val Gly Tyr
115 120 125
Glu Gln Gly Ala Gly Ala Ser Ala Gly Ala Glu Ala Ala Ala Ser Ser
130 135 140
Ala Gly Ala Gly Tyr Gly Gly Gln Ala Gly Tyr Gly Gln Gly Ala Gly
145 150 155 160
Ala Ser Ala Gly Ala Ala Ala Ala
165
<210> 93
<211> 166
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 93
Gly Gly Ala Gly Gln Gly Gly Tyr Gly Gly Leu Gly Gly Gln Gly Ala
1 5 10 15
Gly Gln Gly Gly Leu Gly Gly Gln Arg Ala Gly Ala Ala Ala Ala Ala
20 25 30
Ala Gly Gly Ala Gly Gln Gly Gly Tyr Gly Gly Leu Gly Ser Gln Gly
35 40 45
Ala Gly Arg Gly Gly Tyr Gly Gly Val Gly Ser Gly Ala Ser Ala Ala
50 55 60
Ser Ala Ala Ala Ser Arg Leu Ser Ser Pro Glu Ala Ser Ser Arg Val
65 70 75 80
Ser Ser Ala Val Ser Asn Leu Val Ser Ser Gly Pro Thr Asn Ser Ala
85 90 95
Ala Leu Ser Ser Thr Ile Ser Asn Val Val Ser Gln Ile Ser Ala Ser
100 105 110
Asn Pro Gly Leu Ser Gly Cys Asp Val Leu Val Gln Ala Leu Leu Glu
115 120 125
Val Val Ser Ala Leu Ile Gln Ile Leu Gly Ser Ser Ser Ile Gly Gln
130 135 140
Val Asn Tyr Gly Thr Ala Gly Gln Ala Ala Gln Ile Val Gly Gln Ser
145 150 155 160
Val Tyr Gln Ala Leu Gly
165
<210> 94
<211> 166
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 94
Gly Gly Tyr Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Gly Ala Gly
1 5 10 15
Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ser Ser Ser
20 25 30
Ala Ala Ala Val Gly Gly Tyr Gly Pro Ser Ser Gly Leu Gln Gly Pro
35 40 45
Ala Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ala Ala Ser Ala Ala Ala
50 55 60
Ala Ala Gly Ala Ser Arg Leu Ser Ser Pro Gln Ala Ser Ser Arg Val
65 70 75 80
Ser Ser Ala Val Ser Ser Leu Val Ser Ser Gly Pro Thr Asn Ser Ala
85 90 95
Ala Leu Thr Asn Thr Ile Ser Ser Val Val Ser Gln Ile Ser Ala Ser
100 105 110
Asn Pro Gly Leu Ser Gly Cys Asp Val Leu Ile Gln Ala Leu Leu Glu
115 120 125
Ile Val Ser Ala Leu Val His Ile Leu Gly Tyr Ser Ser Ile Gly Gln
130 135 140
Ile Asn Tyr Asp Ala Ala Ala Gln Tyr Ala Ser Leu Val Gly Gln Ser
145 150 155 160
Val Ala Gln Ala Leu Ala
165
<210> 95
<211> 166
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 95
Gly Gly Ala Gly Ala Gly Gln Gly Ser Tyr Gly Gly Gln Gly Gly Tyr
1 5 10 15
Gly Gln Gly Gly Ala Gly Ala Ala Thr Ala Thr Ala Ala Ala Ala Gly
20 25 30
Gly Ala Gly Ser Gly Gln Gly Gly Tyr Gly Gly Gln Gly Gly Leu Gly
35 40 45
Gly Tyr Gly Gln Gly Ala Gly Ala Gly Ala Ala Ala Ala Ala Ala Ala
50 55 60
Ala Ala Gly Gly Ala Gly Ala Gly Gln Gly Gly Tyr Gly Gly Gln Gly
65 70 75 80
Gly Gln Gly Gly Tyr Gly Gln Gly Ala Gly Ala Gly Ala Ala Ala Ala
85 90 95
Ala Ala Gly Gly Ala Gly Ala Gly Gln Gly Gly Tyr Gly Gly Gln Gly
100 105 110
Gly Tyr Gly Gln Gly Gly Gly Ala Gly Ala Ala Ala Ala Ala Ala Ala
115 120 125
Ala Ser Gly Gly Ser Gly Ser Gly Gln Gly Gly Tyr Gly Gly Gln Gly
130 135 140
Gly Leu Gly Gly Tyr Gly Gln Gly Ala Gly Ala Gly Ala Gly Ala Ala
145 150 155 160
Ala Ser Ala Ala Ala Ala
165
<210> 96
<211> 165
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 96
Gly Gln Gly Gly Gln Gly Gly Tyr Gly Arg Gln Ser Gln Gly Ala Gly
1 5 10 15
Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly
20 25 30
Ser Gly Gln Gly Gly Tyr Gly Gly Gln Gly Gln Gly Gly Tyr Gly Gln
35 40 45
Ser Ser Ala Ser Ala Ser Ala Ala Ala Ser Ala Ala Ser Thr Val Ala
50 55 60
Asn Ser Val Ser Arg Leu Ser Ser Pro Ser Ala Val Ser Arg Val Ser
65 70 75 80
Ser Ala Val Ser Ser Leu Val Ser Asn Gly Gln Val Asn Met Ala Ala
85 90 95
Leu Pro Asn Ile Ile Ser Asn Ile Ser Ser Ser Val Ser Ala Ser Ala
100 105 110
Pro Gly Ala Ser Gly Cys Glu Val Ile Val Gln Ala Leu Leu Glu Val
115 120 125
Ile Thr Ala Leu Val Gln Ile Val Ser Ser Ser Ser Val Gly Tyr Ile
130 135 140
Asn Pro Ser Ala Val Asn Gln Ile Thr Asn Val Val Ala Asn Ala Met
145 150 155 160
Ala Gln Val Met Gly
165
<210> 97
<211> 164
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 97
Gly Gly Ala Gly Gln Gly Gly Tyr Gly Gly Leu Gly Gly Gln Gly Ser
1 5 10 15
Gly Ala Ala Ala Ala Gly Thr Gly Gln Gly Gly Tyr Gly Ser Leu Gly
20 25 30
Gly Gln Gly Ala Gly Ala Ala Gly Ala Ala Ala Ala Ala Val Gly Gly
35 40 45
Ala Gly Gln Gly Gly Tyr Gly Gly Val Gly Ser Ala Ala Ala Ser Ala
50 55 60
Ala Ala Ser Arg Leu Ser Ser Pro Glu Ala Ser Ser Arg Val Ser Ser
65 70 75 80
Ala Val Ser Asn Leu Val Ser Ser Gly Pro Thr Asn Ser Ala Ala Leu
85 90 95
Ser Asn Thr Ile Ser Asn Val Val Ser Gln Ile Ser Ser Ser Asn Pro
100 105 110
Gly Leu Ser Gly Cys Asp Val Leu Val Gln Ala Leu Leu Glu Val Val
115 120 125
Ser Ala Leu Ile His Ile Leu Gly Ser Ser Ser Ile Gly Gln Val Asn
130 135 140
Tyr Gly Ser Ala Gly Gln Ala Thr Gln Ile Val Gly Gln Ser Val Tyr
145 150 155 160
Gln Ala Leu Gly
<210> 98
<211> 164
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 98
Gly Ala Gly Ala Gly Gly Ala Gly Gly Tyr Gly Ala Gly Gln Gly Tyr
1 5 10 15
Gly Ala Gly Ala Gly Ala Gly Ala Ala Ala Gly Ala Gly Ala Gly Gly
20 25 30
Ala Arg Gly Tyr Gly Ala Arg Gln Gly Tyr Gly Ser Gly Ala Gly Ala
35 40 45
Gly Ala Gly Ala Arg Ala Gly Gly Ala Gly Gly Tyr Gly Arg Gly Ala
50 55 60
Gly Ala Gly Ala Ala Ala Ala Ser Gly Ala Gly Ala Gly Gly Tyr Gly
65 70 75 80
Ala Gly Gln Gly Tyr Gly Ala Gly Ala Gly Ala Val Ala Ser Ala Ala
85 90 95
Ala Gly Ala Gly Ser Gly Ala Gly Gly Ala Gly Gly Tyr Gly Arg Gly
100 105 110
Ala Gly Ala Val Ala Gly Ala Gly Ala Gly Gly Ala Gly Gly Tyr Gly
115 120 125
Ala Gly Ala Gly Ala Ala Ala Gly Val Gly Ala Gly Gly Ser Gly Gly
130 135 140
Tyr Gly Gly Arg Gln Gly Gly Tyr Ser Ala Gly Ala Gly Ala Gly Ala
145 150 155 160
Ala Ala Ala Ala
<210> 99
<211> 163
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 99
Gly Gln Gly Gly Gln Gly Gly Tyr Gly Gly Leu Gly Gln Gly Gly Tyr
1 5 10 15
Gly Gln Gly Ala Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala
20 25 30
Ala Ala Gly Arg Gly Gln Gly Gly Tyr Gly Gln Gly Ser Gly Gly Asn
35 40 45
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly Gln Gly
50 55 60
Gly Gln Gly Gly Gln Gly Gly Gln Gly Gln Gly Gly Tyr Gly Gln Gly
65 70 75 80
Ala Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
85 90 95
Ala Ala Ala Gly Arg Gly Gln Gly Gly Tyr Gly Gln Gly Ala Gly Gly
100 105 110
Asn Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ser Gly Gln
115 120 125
Gly Gly Gln Gly Gly Gln Gly Gly Gln Gly Gln Gly Gly Tyr Gly Gln
130 135 140
Gly Ala Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
145 150 155 160
Ala Ala Ala
<210> 100
<211> 162
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 100
Gly Gly Tyr Gly Pro Gly Ser Gly Gln Gln Gly Pro Gly Gln Gln Gly
1 5 10 15
Pro Gly Gln Gln Gly Pro Gly Gln Gln Gly Pro Tyr Gly Ala Gly Ala
20 25 30
Ser Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Ser Gly Gln
35 40 45
Gln Gly Pro Gly Val Arg Val Ala Ala Pro Val Ala Ser Ala Ala Ala
50 55 60
Ser Arg Leu Ser Ser Ser Ala Ala Ser Ser Arg Val Ser Ser Ala Val
65 70 75 80
Ser Ser Leu Val Ser Ser Gly Pro Thr Thr Pro Ala Ala Leu Ser Asn
85 90 95
Thr Ile Ser Ser Ala Val Ser Gln Ile Ser Ala Ser Asn Pro Gly Leu
100 105 110
Ser Gly Cys Asp Val Leu Val Gln Ala Leu Leu Glu Val Val Ser Ala
115 120 125
Leu Val His Ile Leu Gly Ser Ser Ser Val Gly Gln Ile Asn Tyr Gly
130 135 140
Ala Ser Ala Gln Tyr Ala Gln Met Val Gly Gln Ser Val Thr Gln Ala
145 150 155 160
Leu Val
<210> 101
<211> 161
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 101
Gly Ala Gly Ala Gly Gly Ala Gly Tyr Gly Arg Gly Ala Gly Ala Gly
1 5 10 15
Ala Gly Ala Ala Ala Gly Ala Gly Ala Gly Ala Ala Ala Gly Ala Gly
20 25 30
Ala Gly Ala Gly Gly Tyr Gly Gly Gln Gly Gly Tyr Gly Ala Gly Ala
35 40 45
Gly Ala Gly Ala Ala Ala Ala Ala Gly Ala Gly Ala Gly Gly Ala Ala
50 55 60
Gly Tyr Ser Arg Gly Gly Arg Ala Gly Ala Ala Gly Ala Gly Ala Gly
65 70 75 80
Ala Ala Ala Gly Ala Gly Ala Gly Ala Gly Gly Tyr Gly Gly Gln Gly
85 90 95
Gly Tyr Gly Ala Gly Ala Gly Ala Gly Ala Ala Ala Ala Ala Gly Ala
100 105 110
Gly Ser Gly Gly Ala Gly Gly Tyr Gly Arg Gly Ala Gly Ala Gly Ala
115 120 125
Ala Ala Gly Ala Gly Ala Ala Ala Gly Ala Gly Ala Gly Ala Gly Gly
130 135 140
Tyr Gly Gly Gln Gly Gly Tyr Gly Ala Gly Ala Gly Ala Ala Ala Ala
145 150 155 160
Ala
<210> 102
<211> 160
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 102
Gly Ala Gly Ala Gly Arg Gly Gly Tyr Gly Arg Gly Ala Gly Ala Gly
1 5 10 15
Gly Tyr Gly Gly Gln Gly Gly Tyr Gly Ala Gly Ala Gly Ala Gly Ala
20 25 30
Ala Ala Ala Ala Gly Ala Gly Ala Gly Gly Tyr Gly Asp Lys Glu Ile
35 40 45
Ala Cys Trp Ser Arg Cys Arg Tyr Thr Val Ala Ser Thr Thr Ser Arg
50 55 60
Leu Ser Ser Ala Glu Ala Ser Ser Arg Ile Ser Ser Ala Ala Ser Thr
65 70 75 80
Leu Val Ser Gly Gly Tyr Leu Asn Thr Ala Ala Leu Pro Ser Val Ile
85 90 95
Ser Asp Leu Phe Ala Gln Val Gly Ala Ser Ser Pro Gly Val Ser Asp
100 105 110
Ser Glu Val Leu Ile Gln Val Leu Leu Glu Ile Val Ser Ser Leu Ile
115 120 125
His Ile Leu Ser Ser Ser Ser Val Gly Gln Val Asp Phe Ser Ser Val
130 135 140
Gly Ser Ser Ala Ala Ala Val Gly Gln Ser Met Gln Val Val Met Gly
145 150 155 160
<210> 103
<211> 160
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 103
Gly Ala Gly Ala Gly Ala Gly Gly Ala Gly Gly Tyr Gly Arg Gly Ala
1 5 10 15
Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Ala Ala Gly Gln Gly Tyr
20 25 30
Gly Ser Gly Ala Gly Ala Gly Ala Gly Ala Ser Ala Gly Gly Ala Gly
35 40 45
Ser Tyr Gly Arg Gly Ala Gly Ala Gly Ala Ala Ala Ala Ser Gly Ala
50 55 60
Gly Ala Gly Gly Tyr Gly Ala Gly Gln Gly Tyr Gly Ala Gly Ala Gly
65 70 75 80
Ala Val Ala Ser Ala Ala Ala Gly Ala Gly Ser Gly Ala Gly Gly Ala
85 90 95
Gly Gly Tyr Gly Arg Gly Ala Val Ala Gly Ser Gly Ala Gly Ala Gly
100 105 110
Ala Gly Ala Gly Gly Ala Gly Gly Tyr Gly Ala Gly Ala Gly Ala Gly
115 120 125
Ala Ala Ala Gly Ala Val Ala Gly Gly Ser Gly Gly Tyr Gly Gly Arg
130 135 140
Gln Gly Gly Tyr Ser Ala Gly Ala Gly Ala Gly Ala Ala Ala Ala Ala
145 150 155 160
<210> 104
<211> 159
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 104
Gly Pro Gly Gly Tyr Gly Pro Val Gln Gln Gly Pro Ser Gly Pro Gly
1 5 10 15
Ser Ala Ala Gly Pro Gly Gly Tyr Gly Pro Ala Gln Gln Gly Pro Ala
20 25 30
Arg Tyr Gly Pro Gly Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly Ser
35 40 45
Ala Gly Tyr Gly Pro Gly Pro Gln Ala Ser Ala Ala Ala Ser Arg Leu
50 55 60
Ala Ser Pro Asp Ser Gly Ala Arg Val Ala Ser Ala Val Ser Asn Leu
65 70 75 80
Val Ser Ser Gly Pro Thr Ser Ser Ala Ala Leu Ser Ser Val Ile Ser
85 90 95
Asn Ala Val Ser Gln Ile Gly Ala Ser Asn Pro Gly Leu Ser Gly Cys
100 105 110
Asp Val Leu Ile Gln Ala Leu Leu Glu Ile Val Ser Ala Cys Val Thr
115 120 125
Ile Leu Ser Ser Ser Ser Ile Gly Gln Val Asn Tyr Gly Ala Ala Ser
130 135 140
Gln Phe Ala Gln Val Val Gly Gln Ser Val Leu Ser Ala Phe Ser
145 150 155
<210> 105
<211> 156
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 105
Gly Thr Gly Gly Val Gly Gly Leu Phe Leu Ser Ser Gly Asp Phe Gly
1 5 10 15
Arg Gly Gly Ala Gly Ala Gly Ala Gly Ala Ala Ala Ala Ser Ala Ala
20 25 30
Ala Ala Ser Ser Ala Ala Ala Gly Ala Arg Gly Gly Ser Gly Phe Gly
35 40 45
Val Gly Thr Gly Gly Phe Gly Arg Gly Gly Ala Gly Ala Gly Thr Gly
50 55 60
Ala Ala Ala Ala Ser Ala Ala Ala Ala Ser Ala Ala Ala Ala Gly Ala
65 70 75 80
Gly Gly Asp Gly Gly Leu Phe Leu Ser Ser Gly Asp Phe Gly Arg Gly
85 90 95
Gly Ala Gly Ala Gly Ala Gly Ala Ala Ala Ala Ser Ala Ala Ala Ala
100 105 110
Ser Ser Ala Ala Ala Gly Ala Arg Gly Gly Ser Gly Phe Gly Val Gly
115 120 125
Thr Gly Gly Phe Gly Arg Gly Gly Ala Gly Asp Gly Ala Ser Ala Ala
130 135 140
Ala Ala Ser Ala Ala Ala Ala Ser Ala Ala Ala Ala
145 150 155
<210> 106
<211> 153
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 106
Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Gly Ala Gly
1 5 10 15
Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Ser Val Ala Ala
20 25 30
Ala Ala Ser Ala Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly
35 40 45
Pro Val Ala Ser Ala Ala Val Ser Arg Leu Ser Ser Pro Gln Ala Ser
50 55 60
Ser Arg Val Ser Ser Ala Val Ser Ser Leu Val Ser Ser Gly Pro Thr
65 70 75 80
Asn Pro Ala Ala Leu Ser Asn Ala Met Ser Ser Val Val Ser Gln Val
85 90 95
Ser Ala Ser Asn Pro Gly Leu Ser Gly Cys Asp Val Leu Val Gln Ala
100 105 110
Leu Leu Glu Ile Val Ser Ala Leu Val His Ile Leu Gly Ser Ser Ser
115 120 125
Ile Gly Gln Ile Asn Tyr Ala Ala Ser Ser Gln Tyr Ala Gln Met Val
130 135 140
Gly Gln Ser Val Ala Gln Ala Leu Ala
145 150
<210> 107
<211> 153
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 107
Gly Gly Ala Gly Gln Gly Gly Tyr Gly Gly Leu Gly Ser Gln Gly Ala
1 5 10 15
Gly Arg Gly Gly Tyr Gly Gly Gln Gly Ala Gly Ala Ala Ala Ala Ala
20 25 30
Thr Gly Gly Ala Gly Gln Gly Gly Tyr Gly Gly Val Gly Ser Gly Ala
35 40 45
Ser Ala Ala Ser Ala Ala Ala Ser Arg Leu Ser Ser Pro Gln Ala Ser
50 55 60
Ser Arg Val Ser Ser Ala Val Ser Asn Leu Val Ala Ser Gly Pro Thr
65 70 75 80
Asn Ser Ala Ala Leu Ser Ser Thr Ile Ser Asn Ala Val Ser Gln Ile
85 90 95
Gly Ala Ser Asn Pro Gly Leu Ser Gly Cys Asp Val Leu Ile Gln Ala
100 105 110
Leu Leu Glu Val Val Ser Ala Leu Ile His Ile Leu Gly Ser Ser Ser
115 120 125
Ile Gly Gln Val Asn Tyr Gly Ser Ala Gly Gln Ala Thr Gln Ile Val
130 135 140
Gly Gln Ser Val Tyr Gln Ala Leu Gly
145 150
<210> 108
<211> 153
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 108
Gly Gly Ala Gly Gln Gly Gly Tyr Gly Gly Leu Gly Ser Gln Gly Ala
1 5 10 15
Gly Arg Gly Gly Tyr Gly Gly Gln Gly Ala Gly Ala Ala Val Ala Ala
20 25 30
Ile Gly Gly Val Gly Gln Gly Gly Tyr Gly Gly Val Gly Ser Gly Ala
35 40 45
Ser Ala Ala Ser Ala Ala Ala Ser Arg Leu Ser Ser Pro Glu Ala Ser
50 55 60
Ser Arg Val Ser Ser Ala Val Ser Asn Leu Val Ser Ser Gly Pro Thr
65 70 75 80
Asn Ser Ala Ala Leu Ser Ser Thr Ile Ser Asn Val Val Ser Gln Ile
85 90 95
Gly Ala Ser Asn Pro Gly Leu Ser Gly Cys Asp Val Leu Ile Gln Ala
100 105 110
Leu Leu Glu Val Val Ser Ala Leu Val His Ile Leu Gly Ser Ser Ser
115 120 125
Ile Gly Gln Val Asn Tyr Gly Ser Ala Gly Gln Ala Thr Gln Ile Val
130 135 140
Gly Gln Ser Val Tyr Gln Ala Leu Gly
145 150
<210> 109
<211> 152
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 109
Gly Ala Ser Gly Gly Tyr Gly Gly Gly Ala Gly Glu Gly Ala Gly Ala
1 5 10 15
Ala Ala Ala Ala Gly Ala Gly Ala Gly Gly Ala Gly Gly Tyr Gly Gly
20 25 30
Gly Ala Gly Ser Gly Ala Gly Ala Val Ala Arg Ala Gly Ala Gly Gly
35 40 45
Ala Gly Gly Tyr Gly Ser Gly Ile Gly Gly Gly Tyr Gly Ser Gly Ala
50 55 60
Gly Ala Ala Ala Gly Ala Gly Ala Gly Gly Ala Gly Ala Tyr Gly Gly
65 70 75 80
Gly Tyr Gly Thr Gly Ala Gly Ala Gly Ala Arg Gly Ala Asp Ser Ala
85 90 95
Gly Ala Ala Ala Gly Tyr Gly Gly Gly Val Gly Thr Gly Thr Gly Ser
100 105 110
Ser Ala Gly Tyr Gly Arg Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala
115 120 125
Ala Ala Gly Ser Gly Ala Gly Ala Ala Gly Gly Tyr Gly Gly Gly Tyr
130 135 140
Gly Ala Gly Ala Gly Ala Gly Ala
145 150
<210> 110
<211> 152
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 110
Gly Ala Gly Ser Gly Gln Gly Gly Tyr Gly Gly Gln Gly Gly Leu Gly
1 5 10 15
Gly Tyr Gly Gln Gly Ala Gly Ala Gly Ala Ala Ala Gly Ala Ser Gly
20 25 30
Ser Gly Ser Gly Gly Ala Gly Gln Gly Gly Leu Gly Gly Tyr Gly Gln
35 40 45
Gly Ala Gly Ala Gly Ala Ala Ala Ala Ala Ala Gly Ala Ser Gly Ala
50 55 60
Gly Gln Gly Gly Phe Gly Pro Tyr Gly Ser Ser Tyr Gln Ser Ser Thr
65 70 75 80
Ser Tyr Ser Val Thr Ser Gln Gly Ala Ala Gly Gly Leu Gly Gly Tyr
85 90 95
Gly Gln Gly Ser Gly Ala Gly Ala Ala Ala Ala Gly Ala Ala Gly Gln
100 105 110
Gly Gly Gln Gly Gly Tyr Gly Gln Gly Ala Gly Ala Gly Ala Gly Ala
115 120 125
Gly Ala Gly Gln Gly Gly Leu Gly Gly Tyr Gly Gln Gly Ala Gly Ser
130 135 140
Ser Ala Ala Ser Ala Ala Ala Ala
145 150
<210> 111
<211> 151
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 111
Gly Gly Ala Gly Gln Gly Gly Tyr Gly Gly Leu Gly Gly Gln Gly Val
1 5 10 15
Gly Arg Gly Gly Leu Gly Gly Gln Gly Ala Gly Ala Ala Ala Ala Gly
20 25 30
Gly Ala Gly Gln Gly Gly Tyr Gly Gly Val Gly Ser Gly Ala Ser Ala
35 40 45
Ala Ser Ala Ala Ala Ser Arg Leu Ser Ser Pro Gln Ala Ser Ser Arg
50 55 60
Leu Ser Ser Ala Val Ser Asn Leu Val Ala Thr Gly Pro Thr Asn Ser
65 70 75 80
Ala Ala Leu Ser Ser Thr Ile Ser Asn Val Val Ser Gln Ile Gly Ala
85 90 95
Ser Asn Pro Gly Leu Ser Gly Cys Asp Val Leu Ile Gln Ala Leu Leu
100 105 110
Glu Val Val Ser Ala Leu Ile Gln Ile Leu Gly Ser Ser Ser Ile Gly
115 120 125
Gln Val Asn Tyr Gly Ser Ala Gly Gln Ala Thr Gln Ile Val Gly Gln
130 135 140
Ser Val Tyr Gln Ala Leu Gly
145 150
<210> 112
<211> 150
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 112
Gly Ala Gly Ser Gly Gly Ala Gly Gly Tyr Gly Arg Gly Ala Gly Ala
1 5 10 15
Gly Ala Gly Ala Ala Ala Gly Ala Gly Ala Gly Ala Gly Ser Tyr Gly
20 25 30
Gly Gln Gly Gly Tyr Gly Ala Gly Ala Gly Ala Gly Ala Ala Ala Ala
35 40 45
Ala Gly Ala Gly Ala Gly Ala Gly Gly Tyr Gly Arg Gly Ala Gly Ala
50 55 60
Gly Ala Gly Ala Gly Ala Gly Ala Ala Ala Arg Ala Gly Ala Gly Ala
65 70 75 80
Gly Gly Ala Gly Tyr Gly Gly Gln Gly Gly Tyr Gly Ala Gly Ala Gly
85 90 95
Ala Gly Ala Ala Ala Ala Ala Gly Ala Gly Ala Gly Gly Ala Gly Gly
100 105 110
Tyr Gly Arg Gly Ala Gly Ala Gly Ala Gly Ala Ala Ala Gly Ala Gly
115 120 125
Ala Gly Ala Gly Gly Tyr Gly Gly Gln Ser Gly Tyr Gly Ala Gly Ala
130 135 140
Gly Ala Ala Ala Ala Ala
145 150
<210> 113
<211> 150
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 113
Gly Ala Ser Gly Ala Gly Gln Gly Gln Gly Tyr Gly Gln Gln Gly Gln
1 5 10 15
Gly Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gln
20 25 30
Gly Gln Gly Gln Gly Tyr Gly Gln Gln Gly Gln Gly Tyr Gly Gln Gln
35 40 45
Gly Gln Gly Gly Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
50 55 60
Ala Ala Ala Gln Gly Gln Gly Gln Gly Tyr Gly Gln Gln Gly Gln Gly
65 70 75 80
Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Ala Ser Gly Ala Gly
85 90 95
Gln Gly Gln Gly Tyr Gly Gln Gln Gly Gln Gly Gly Ser Ser Ala Ala
100 105 110
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gln Gly Gln
115 120 125
Gly Tyr Gly Gln Gln Gly Gln Gly Ser Ala Ala Ala Ala Ala Ala Ala
130 135 140
Ala Ala Ala Ala Ala Ala
145 150
<210> 114
<211> 945
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 114
Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gly Gly
1 5 10 15
Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Ser Gly Gln Gln Gly
20 25 30
Pro Gly Gly Ala Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly
35 40 45
Pro Gly Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro
50 55 60
Gly Ala Gly Gln Gln Gly Pro Gly Gly Ala Gly Gln Gln Gly Pro Gly
65 70 75 80
Ser Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Gly Gln
85 90 95
Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro
100 105 110
Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala
115 120 125
Ala Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln Arg Ser Gln Gly Pro
130 135 140
Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly
145 150 155 160
Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly
165 170 175
Pro Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr
180 185 190
Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser
195 200 205
Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala
210 215 220
Ala Ala Ala Ala Ala Ala Val Gly Gly Tyr Gly Pro Gly Ala Gly Gln
225 230 235 240
Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro
245 250 255
Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala
260 265 270
Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln
275 280 285
Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr
290 295 300
Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro
305 310 315 320
Gly Ala Gly Gln Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly
325 330 335
Gly Gln Gly Pro Tyr Gly Ser Gly Gln Gln Gly Pro Gly Gly Ala Gly
340 345 350
Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ala Ala
355 360 365
Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln
370 375 380
Gly Pro Gly Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly
385 390 395 400
Gly Gln Gly Pro Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser
405 410 415
Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro
420 425 430
Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr
435 440 445
Gly Pro Gly Ala Gly Gln Arg Ser Gln Gly Pro Gly Gly Gln Gly Pro
450 455 460
Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly
465 470 475 480
Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Ser
485 490 495
Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Ala Gly
500 505 510
Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly
515 520 525
Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ala Ala Ala Ala Ala
530 535 540
Ala Val Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser
545 550 555 560
Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro
565 570 575
Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly
580 585 590
Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly
595 600 605
Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala Ala
610 615 620
Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln
625 630 635 640
Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr
645 650 655
Gly Ser Gly Gln Gln Gly Pro Gly Gly Ala Gly Gln Gln Gly Pro Gly
660 665 670
Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ala Ala Ala Ala Ala Ala Ala
675 680 685
Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Gly Ala
690 695 700
Gly Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Gly Gln Gly Pro Tyr
705 710 715 720
Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser
725 730 735
Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala
740 745 750
Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Ala Gly
755 760 765
Gln Arg Ser Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala
770 775 780
Gly Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln
785 790 795 800
Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala Ala Ala Ala Ala
805 810 815
Ala Ala Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly
820 825 830
Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly
835 840 845
Pro Tyr Gly Pro Gly Ala Ala Ala Ala Ala Ala Ala Val Gly Gly Tyr
850 855 860
Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser
865 870 875 880
Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala
885 890 895
Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln
900 905 910
Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro
915 920 925
Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala
930 935 940
Ala
945
<210> 115
<211> 89
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 115
Met Arg Phe Pro Ser Ile Phe Thr Ala Val Leu Phe Ala Ala Ser Ser
1 5 10 15
Ala Leu Ala Ala Pro Val Asn Thr Thr Thr Glu Asp Glu Thr Ala Gln
20 25 30
Ile Pro Ala Glu Ala Val Ile Gly Tyr Leu Asp Leu Glu Gly Asp Phe
35 40 45
Asp Val Ala Val Leu Pro Phe Ser Asn Ser Thr Asn Asn Gly Leu Leu
50 55 60
Phe Ile Asn Thr Thr Ile Ala Ser Ile Ala Ala Lys Glu Glu Gly Val
65 70 75 80
Ser Leu Asp Lys Arg Glu Ala Glu Ala
85
<210> 116
<211> 48
<212> PRT
<213> Saccharomyces cerivisae
<400> 116
Met Glu Gly Gly Glu Glu Glu Val Glu Arg Ile Pro Asp Glu Leu Phe
1 5 10 15
Asp Thr Lys Lys Lys His Leu Leu Asp Lys Leu Ile Arg Val Gly Ile
20 25 30
Ile Leu Val Leu Leu Ile Trp Gly Thr Val Leu Leu Leu Lys Ser Ile
35 40 45
<210> 117
<211> 43
<212> PRT
<213> Saccharomyces cerivisae
<400> 117
Met Phe Phe Asn Arg Leu Ser Ala Gly Lys Leu Leu Val Pro Leu Ser
1 5 10 15
Val Val Leu Tyr Ala Leu Phe Val Val Ile Leu Pro Leu Gln Asn Ser
20 25 30
Phe His Ser Ser Asn Val Leu Val Arg Gly Ala
35 40
<210> 118
<211> 26
<212> PRT
<213> Saccharomyces cerivisae
<400> 118
Met Pro Phe Gly Ile Asp Asn Thr Asp Phe Thr Val Leu Ala Gly Leu
1 5 10 15
Val Leu Ala Val Leu Leu Tyr Val Lys Arg
20 25
<210> 119
<211> 17
<212> PRT
<213> Saccharomyces cerivisae
<400> 119
Met Lys Pro Gln Cys Ile Leu Ile Ser Leu Leu Val Asn Leu Ala Tyr
1 5 10 15
Ala
<210> 120
<211> 24
<212> PRT
<213> Saccharomyces cerivisae
<400> 120
Met Ile Ser Ala Asn Ser Leu Leu Ile Ser Thr Leu Cys Ala Phe Ala
1 5 10 15
Ile Ala Thr Pro Leu Ser Lys Arg
20
<210> 121
<211> 19
<212> PRT
<213> Saccharomyces cerivisae
<400> 121
Met Leu Gln Ser Val Val Phe Phe Ala Leu Leu Thr Phe Ala Ser Ser
1 5 10 15
Val Ser Ala
<210> 122
<211> 21
<212> PRT
<213> Rattus norvegicus
<400> 122
Met Arg Leu Ala Val Val Cys Leu Cys Leu Phe Gly Leu Ala Ser Cys
1 5 10 15
Leu Pro Val Lys Val
20
<210> 123
<211> 31
<212> PRT
<213> Pichia pastoris
<400> 123
Met Leu Ser Leu Lys Pro Ser Trp Leu Thr Leu Ala Ala Leu Met Tyr
1 5 10 15
Ala Met Leu Leu Val Val Val Pro Phe Ala Lys Pro Val Arg Ala
20 25 30
<210> 124
<211> 23
<212> PRT
<213> Pichia pastoris
<400> 124
Met Ser Phe Ser Ser Asn Val Pro Gln Leu Phe Leu Leu Leu Val Leu
1 5 10 15
Leu Thr Asn Ile Val Ser Gly
20
<210> 125
<211> 16
<212> PRT
<213> Pichia pastoris
<400> 125
Met Asn Leu Tyr Leu Ile Thr Leu Leu Phe Ala Ser Leu Cys Ser Ala
1 5 10 15
<210> 126
<211> 19
<212> PRT
<213> Saccharomyces cerivisae
<400> 126
Met His Trp Ala Ala Ala Val Ala Ile Phe Phe Ile Val Val Thr Lys
1 5 10 15
Phe Leu Gln
<210> 127
<211> 18
<212> PRT
<213> Pichia pastoris
<400> 127
Met Arg Phe Ser Asn Phe Leu Thr Val Ser Ala Leu Leu Thr Gly Ala
1 5 10 15
Leu Gly
<210> 128
<211> 20
<212> PRT
<213> Saccharomyces cerivisae
<400> 128
Met Ser Leu Leu Tyr Ile Ile Leu Leu Phe Thr Gln Phe Leu Leu Leu
1 5 10 15
Pro Thr Asp Ala
20
<210> 129
<211> 44
<212> PRT
<213> Pichia pastoris
<400> 129
Met Ala Lys Ala Asp Gly Ser Leu Leu Tyr Tyr Asn Pro His Asn Pro
1 5 10 15
Pro Arg Arg Tyr Tyr Phe Tyr Met Ala Ile Phe Ala Val Ser Val Ile
20 25 30
Cys Val Leu Tyr Gly Pro Ser Gln Gln Leu Ser Ser
35 40
<210> 130
<211> 90
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 130
Met Lys Leu Ser Thr Asn Leu Ile Leu Ala Ile Ala Ala Ala Ser Ala
1 5 10 15
Val Val Ser Ala Ala Pro Val Asn Thr Thr Thr Glu Asp Glu Thr Ala
20 25 30
Gln Ile Pro Ala Glu Ala Val Ile Gly Tyr Ser Asp Leu Glu Gly Asp
35 40 45
Phe Asp Val Ala Val Leu Pro Phe Ser Asn Ser Thr Asn Asn Gly Leu
50 55 60
Leu Phe Ile Asn Thr Thr Ile Ala Ser Ile Ala Ala Lys Glu Glu Gly
65 70 75 80
Val Ser Leu Glu Lys Arg Glu Ala Glu Ala
85 90
<210> 131
<211> 118
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 131
Met Glu Gly Gly Glu Glu Glu Val Glu Arg Ile Pro Asp Glu Leu Phe
1 5 10 15
Asp Thr Lys Lys Lys His Leu Leu Asp Lys Leu Ile Arg Val Gly Ile
20 25 30
Ile Leu Val Leu Leu Ile Trp Gly Thr Val Leu Leu Leu Lys Ser Ile
35 40 45
Ala Pro Val Asn Thr Thr Thr Glu Asp Glu Thr Ala Gln Ile Pro Ala
50 55 60
Glu Ala Val Ile Gly Tyr Ser Asp Leu Glu Gly Asp Phe Asp Val Ala
65 70 75 80
Val Leu Pro Phe Ser Asn Ser Thr Asn Asn Gly Leu Leu Phe Ile Asn
85 90 95
Thr Thr Ile Ala Ser Ile Ala Ala Lys Glu Glu Gly Val Ser Leu Glu
100 105 110
Lys Arg Glu Ala Glu Ala
115
<210> 132
<211> 113
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 132
Met Phe Phe Asn Arg Leu Ser Ala Gly Lys Leu Leu Val Pro Leu Ser
1 5 10 15
Val Val Leu Tyr Ala Leu Phe Val Val Ile Leu Pro Leu Gln Asn Ser
20 25 30
Phe His Ser Ser Asn Val Leu Val Arg Gly Ala Ala Pro Val Asn Thr
35 40 45
Thr Thr Glu Asp Glu Thr Ala Gln Ile Pro Ala Glu Ala Val Ile Gly
50 55 60
Tyr Ser Asp Leu Glu Gly Asp Phe Asp Val Ala Val Leu Pro Phe Ser
65 70 75 80
Asn Ser Thr Asn Asn Gly Leu Leu Phe Ile Asn Thr Thr Ile Ala Ser
85 90 95
Ile Ala Ala Lys Glu Glu Gly Val Ser Leu Glu Lys Arg Glu Ala Glu
100 105 110
Ala
<210> 133
<211> 96
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 133
Met Pro Phe Gly Ile Asp Asn Thr Asp Phe Thr Val Leu Ala Gly Leu
1 5 10 15
Val Leu Ala Val Leu Leu Tyr Val Lys Arg Ala Pro Val Asn Thr Thr
20 25 30
Thr Glu Asp Glu Thr Ala Gln Ile Pro Ala Glu Ala Val Ile Gly Tyr
35 40 45
Ser Asp Leu Glu Gly Asp Phe Asp Val Ala Val Leu Pro Phe Ser Asn
50 55 60
Ser Thr Asn Asn Gly Leu Leu Phe Ile Asn Thr Thr Ile Ala Ser Ile
65 70 75 80
Ala Ala Lys Glu Glu Gly Val Ser Leu Glu Lys Arg Glu Ala Glu Ala
85 90 95
<210> 134
<211> 87
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 134
Met Lys Pro Gln Cys Ile Leu Ile Ser Leu Leu Val Asn Leu Ala Tyr
1 5 10 15
Ala Ala Pro Val Asn Thr Thr Thr Glu Asp Glu Thr Ala Gln Ile Pro
20 25 30
Ala Glu Ala Val Ile Gly Tyr Ser Asp Leu Glu Gly Asp Phe Asp Val
35 40 45
Ala Val Leu Pro Phe Ser Asn Ser Thr Asn Asn Gly Leu Leu Phe Ile
50 55 60
Asn Thr Thr Ile Ala Ser Ile Ala Ala Lys Glu Glu Gly Val Ser Leu
65 70 75 80
Glu Lys Arg Glu Ala Glu Ala
85
<210> 135
<211> 94
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 135
Met Ile Ser Ala Asn Ser Leu Leu Ile Ser Thr Leu Cys Ala Phe Ala
1 5 10 15
Ile Ala Thr Pro Leu Ser Lys Arg Ala Pro Val Asn Thr Thr Thr Glu
20 25 30
Asp Glu Thr Ala Gln Ile Pro Ala Glu Ala Val Ile Gly Tyr Ser Asp
35 40 45
Leu Glu Gly Asp Phe Asp Val Ala Val Leu Pro Phe Ser Asn Ser Thr
50 55 60
Asn Asn Gly Leu Leu Phe Ile Asn Thr Thr Ile Ala Ser Ile Ala Ala
65 70 75 80
Lys Glu Glu Gly Val Ser Leu Glu Lys Arg Glu Ala Glu Ala
85 90
<210> 136
<211> 89
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 136
Met Leu Gln Ser Val Val Phe Phe Ala Leu Leu Thr Phe Ala Ser Ser
1 5 10 15
Val Ser Ala Ala Pro Val Asn Thr Thr Thr Glu Asp Glu Thr Ala Gln
20 25 30
Ile Pro Ala Glu Ala Val Ile Gly Tyr Ser Asp Leu Glu Gly Asp Phe
35 40 45
Asp Val Ala Val Leu Pro Phe Ser Asn Ser Thr Asn Asn Gly Leu Leu
50 55 60
Phe Ile Asn Thr Thr Ile Ala Ser Ile Ala Ala Lys Glu Glu Gly Val
65 70 75 80
Ser Leu Glu Lys Arg Glu Ala Glu Ala
85
<210> 137
<211> 91
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 137
Met Arg Leu Ala Val Val Cys Leu Cys Leu Phe Gly Leu Ala Ser Cys
1 5 10 15
Leu Pro Val Lys Val Ala Pro Val Asn Thr Thr Thr Glu Asp Glu Thr
20 25 30
Ala Gln Ile Pro Ala Glu Ala Val Ile Gly Tyr Ser Asp Leu Glu Gly
35 40 45
Asp Phe Asp Val Ala Val Leu Pro Phe Ser Asn Ser Thr Asn Asn Gly
50 55 60
Leu Leu Phe Ile Asn Thr Thr Ile Ala Ser Ile Ala Ala Lys Glu Glu
65 70 75 80
Gly Val Ser Leu Glu Lys Arg Glu Ala Glu Ala
85 90
<210> 138
<211> 101
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 138
Met Leu Ser Leu Lys Pro Ser Trp Leu Thr Leu Ala Ala Leu Met Tyr
1 5 10 15
Ala Met Leu Leu Val Val Val Pro Phe Ala Lys Pro Val Arg Ala Ala
20 25 30
Pro Val Asn Thr Thr Thr Glu Asp Glu Thr Ala Gln Ile Pro Ala Glu
35 40 45
Ala Val Ile Gly Tyr Ser Asp Leu Glu Gly Asp Phe Asp Val Ala Val
50 55 60
Leu Pro Phe Ser Asn Ser Thr Asn Asn Gly Leu Leu Phe Ile Asn Thr
65 70 75 80
Thr Ile Ala Ser Ile Ala Ala Lys Glu Glu Gly Val Ser Leu Glu Lys
85 90 95
Arg Glu Ala Glu Ala
100
<210> 139
<211> 93
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 139
Met Ser Phe Ser Ser Asn Val Pro Gln Leu Phe Leu Leu Leu Val Leu
1 5 10 15
Leu Thr Asn Ile Val Ser Gly Ala Pro Val Asn Thr Thr Thr Glu Asp
20 25 30
Glu Thr Ala Gln Ile Pro Ala Glu Ala Val Ile Gly Tyr Ser Asp Leu
35 40 45
Glu Gly Asp Phe Asp Val Ala Val Leu Pro Phe Ser Asn Ser Thr Asn
50 55 60
Asn Gly Leu Leu Phe Ile Asn Thr Thr Ile Ala Ser Ile Ala Ala Lys
65 70 75 80
Glu Glu Gly Val Ser Leu Glu Lys Arg Glu Ala Glu Ala
85 90
<210> 140
<211> 86
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 140
Met Asn Leu Tyr Leu Ile Thr Leu Leu Phe Ala Ser Leu Cys Ser Ala
1 5 10 15
Ala Pro Val Asn Thr Thr Thr Glu Asp Glu Thr Ala Gln Ile Pro Ala
20 25 30
Glu Ala Val Ile Gly Tyr Ser Asp Leu Glu Gly Asp Phe Asp Val Ala
35 40 45
Val Leu Pro Phe Ser Asn Ser Thr Asn Asn Gly Leu Leu Phe Ile Asn
50 55 60
Thr Thr Ile Ala Ser Ile Ala Ala Lys Glu Glu Gly Val Ser Leu Glu
65 70 75 80
Lys Arg Glu Ala Glu Ala
85
<210> 141
<211> 89
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 141
Met His Trp Ala Ala Ala Val Ala Ile Phe Phe Ile Val Val Thr Lys
1 5 10 15
Phe Leu Gln Ala Pro Val Asn Thr Thr Thr Glu Asp Glu Thr Ala Gln
20 25 30
Ile Pro Ala Glu Ala Val Ile Gly Tyr Ser Asp Leu Glu Gly Asp Phe
35 40 45
Asp Val Ala Val Leu Pro Phe Ser Asn Ser Thr Asn Asn Gly Leu Leu
50 55 60
Phe Ile Asn Thr Thr Ile Ala Ser Ile Ala Ala Lys Glu Glu Gly Val
65 70 75 80
Ser Leu Glu Lys Arg Glu Ala Glu Ala
85
<210> 142
<211> 88
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 142
Met Arg Phe Ser Asn Phe Leu Thr Val Ser Ala Leu Leu Thr Gly Ala
1 5 10 15
Leu Gly Ala Pro Val Asn Thr Thr Thr Glu Asp Glu Thr Ala Gln Ile
20 25 30
Pro Ala Glu Ala Val Ile Gly Tyr Ser Asp Leu Glu Gly Asp Phe Asp
35 40 45
Val Ala Val Leu Pro Phe Ser Asn Ser Thr Asn Asn Gly Leu Leu Phe
50 55 60
Ile Asn Thr Thr Ile Ala Ser Ile Ala Ala Lys Glu Glu Gly Val Ser
65 70 75 80
Leu Glu Lys Arg Glu Ala Glu Ala
85
<210> 143
<211> 90
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 143
Met Ser Leu Leu Tyr Ile Ile Leu Leu Phe Thr Gln Phe Leu Leu Leu
1 5 10 15
Pro Thr Asp Ala Ala Pro Val Asn Thr Thr Thr Glu Asp Glu Thr Ala
20 25 30
Gln Ile Pro Ala Glu Ala Val Ile Gly Tyr Ser Asp Leu Glu Gly Asp
35 40 45
Phe Asp Val Ala Val Leu Pro Phe Ser Asn Ser Thr Asn Asn Gly Leu
50 55 60
Leu Phe Ile Asn Thr Thr Ile Ala Ser Ile Ala Ala Lys Glu Glu Gly
65 70 75 80
Val Ser Leu Glu Lys Arg Glu Ala Glu Ala
85 90
<210> 144
<211> 37
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 144
Ala Pro Val Ala Pro Ala Glu Glu Ala Ala Asn His Leu His Lys Arg
1 5 10 15
Ala Tyr Tyr Thr Asp Thr Thr Lys Thr His Thr Phe Thr Glu Val Val
20 25 30
Thr Val Tyr Arg Thr
35
<210> 145
<211> 483
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 145
Ala Asn Leu Asn Gly Thr Leu Met Gln Tyr Phe Glu Trp Tyr Met Pro
1 5 10 15
Asn Asp Gly Gln His Trp Lys Arg Leu Gln Asn Asp Ser Ala Tyr Leu
20 25 30
Ala Glu His Gly Ile Thr Ala Val Trp Ile Pro Pro Ala Tyr Lys Gly
35 40 45
Thr Ser Gln Asp Asp Val Gly Tyr Gly Ala Tyr Asp Leu Tyr Asp Leu
50 55 60
Gly Glu Phe His Gln Lys Gly Thr Val Arg Thr Lys Tyr Gly Thr Lys
65 70 75 80
Gly Glu Leu Gln Ser Ala Ile Asn Ser Leu His Ser Arg Asp Ile Asn
85 90 95
Val Tyr Gly Asp Val Val Ile Asn His Lys Gly Gly Ala Asp Ala Thr
100 105 110
Glu Asp Val Thr Ala Val Glu Val Asp Pro Ala Asp Arg Asn Arg Val
115 120 125
Thr Ser Gly Glu Gln Arg Ile Lys Ala Trp Thr His Phe Gln Phe Pro
130 135 140
Gly Arg Gly Ser Thr Tyr Ser Asp Phe Lys Trp His Trp Tyr His Phe
145 150 155 160
Asp Gly Thr Asp Trp Asp Glu Ser Arg Lys Leu Asn Arg Ile Tyr Lys
165 170 175
Phe Gln Gly Lys Ala Trp Asp Trp Glu Val Ser Asn Val Asn Gly Asn
180 185 190
Tyr Asp Tyr Leu Met Tyr Ala Asp Ile Asp Tyr Asp His Pro Asp Ala
195 200 205
Thr Ala Glu Ile Lys Arg Trp Gly Thr Trp Tyr Ala Asn Glu Leu Gln
210 215 220
Leu Asp Gly Phe Arg Leu Asp Ala Val Lys His Ile Lys Phe Ser Phe
225 230 235 240
Leu Arg Asp Trp Val Asn His Val Arg Glu Lys Thr Gly Lys Glu Met
245 250 255
Phe Thr Val Ala Glu Tyr Trp Gln Asn Asp Leu Gly Ala Leu Glu Asn
260 265 270
Tyr Leu Asn Lys Thr Asn Phe Asn His Ser Val Phe Asp Val Pro Leu
275 280 285
His Tyr Gln Phe His Ala Ala Ser Thr Gln Gly Gly Gly Tyr Asp Met
290 295 300
Arg Lys Leu Leu Asn Gly Thr Val Val Ser Lys His Pro Val Lys Ala
305 310 315 320
Val Thr Phe Val Asp Asn His Asp Thr Gln Pro Gly Gln Ser Leu Glu
325 330 335
Ser Thr Val Gln Thr Trp Phe Lys Pro Leu Ala Tyr Ala Phe Ile Leu
340 345 350
Thr Arg Glu Ala Gly Tyr Pro Gln Ile Phe Tyr Gly Asp Met Tyr Gly
355 360 365
Thr Lys Gly Ala Ser Gln Arg Glu Ile Pro Ala Leu Lys His Lys Ile
370 375 380
Glu Pro Ile Leu Lys Ala Arg Ile Gln Tyr Ala Tyr Gly Ala Gln His
385 390 395 400
Asp Tyr Phe Asp His His Asp Ile Val Gly Trp Thr Arg Glu Gly Asp
405 410 415
Ser Ser Val Ala Asn Ser Gly Leu Ala Ala Leu Ile Thr Asp Gly Pro
420 425 430
Gly Gly Thr Lys Arg Met Tyr Val Gly Arg Gln Asn Ala Gly Glu Thr
435 440 445
Trp His Asp Ile Thr Gly Asn Arg Ser Asp Ser Val Val Ile Asn Ala
450 455 460
Glu Gly Trp Gly Glu Phe His Val Asn Gly Gly Ser Val Ser Ile Tyr
465 470 475 480
Val Gln Arg
<210> 146
<211> 235
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<400> 146
Thr Ala Leu Thr Glu Gly Ala Lys Leu Phe Glu Lys Glu Ile Pro Tyr
1 5 10 15
Ile Thr Glu Leu Glu Gly Asp Val Glu Gly Met Lys Phe Ile Ile Lys
20 25 30
Gly Glu Gly Thr Gly Asp Ala Thr Thr Gly Thr Ile Lys Ala Lys Tyr
35 40 45
Ile Cys Thr Thr Gly Asp Leu Pro Val Pro Trp Ala Thr Leu Val Ser
50 55 60
Thr Leu Ser Tyr Gly Val Gln Cys Phe Ala Lys Tyr Pro Ser His Ile
65 70 75 80
Lys Asp Phe Phe Lys Ser Ala Met Pro Glu Gly Tyr Thr Gln Glu Arg
85 90 95
Thr Ile Ser Phe Glu Gly Asp Gly Val Tyr Lys Thr Arg Ala Met Val
100 105 110
Thr Tyr Glu Arg Gly Ser Ile Tyr Asn Arg Val Thr Leu Thr Gly Glu
115 120 125
Asn Phe Lys Lys Asp Gly His Ile Leu Arg Lys Asn Val Ala Phe Gln
130 135 140
Cys Pro Pro Ser Ile Leu Tyr Ile Leu Pro Asp Thr Val Asn Asn Gly
145 150 155 160
Ile Arg Val Glu Phe Asn Gln Ala Tyr Asp Ile Glu Gly Val Thr Glu
165 170 175
Lys Leu Val Thr Lys Cys Ser Gln Met Asn Arg Pro Leu Ala Gly Ser
180 185 190
Ala Ala Val His Ile Pro Arg Tyr His His Ile Thr Tyr His Thr Lys
195 200 205
Leu Ser Lys Asp Arg Asp Glu Arg Arg Asp His Met Cys Leu Val Glu
210 215 220
Val Val Lys Ala Val Asp Leu Asp Thr Tyr Gln
225 230 235
<210> 147
<211> 64
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<220>
<221> MISC_FEATURE
<222> (4)..(8)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (12)..(16)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (20)..(24)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (28)..(32)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (36)..(40)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (44)..(48)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (52)..(56)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (60)..(64)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1)..(64)
<223> This region may encompass 4-8 "GPG-X1" repeating units, wherein
X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some
positions may be absent
<400> 147
Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa
1 5 10 15
Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa
20 25 30
Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa
35 40 45
Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa
50 55 60
<210> 148
<211> 20
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic peptide
<220>
<221> MISC_FEATURE
<222> (1)..(20)
<223> This sequence may encompass 6-20 residues
<400> 148
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
1 5 10 15
Ala Ala Ala Ala
20
<210> 149
<211> 1800
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic polypeptide
<220>
<221> MISC_FEATURE
<222> (7)..(11)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (15)..(19)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (23)..(27)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (31)..(35)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (39)..(43)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (47)..(51)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (55)..(59)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (63)..(67)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (4)..(67)
<223> This region may encompass 4-8 repeating "GPG-X1" repeating units,
wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some
positions may be absent
<220>
<221> MISC_FEATURE
<222> (71)..(90)
<223> This region may encompass 6-20 residues
<220>
<221> MISC_FEATURE
<222> (97)..(101)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (105)..(109)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (113)..(117)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (121)..(125)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (129)..(133)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (137)..(141)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (145)..(149)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (153)..(157)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (94)..(157)
<223> This region may encompass 4-8 repeating "GPG-X1" repeating units,
wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some
positions may be absent
<220>
<221> MISC_FEATURE
<222> (161)..(180)
<223> This region may encompass 6-20 residues
<220>
<221> MISC_FEATURE
<222> (187)..(191)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (195)..(199)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (203)..(207)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (211)..(215)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (219)..(223)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (227)..(231)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (235)..(239)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (243)..(247)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (184)..(247)
<223> This region may encompass 4-8 repeating "GPG-X1" repeating units,
wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some
positions may be absent
<220>
<221> MISC_FEATURE
<222> (251)..(270)
<223> This region may encompass 6-20 residues
<220>
<221> MISC_FEATURE
<222> (277)..(281)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (285)..(289)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (293)..(297)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (301)..(305)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (309)..(313)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (317)..(321)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (325)..(329)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (333)..(337)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (274)..(337)
<223> This region may encompass 4-8 repeating "GPG-X1" repeating units,
wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some
positions may be absent
<220>
<221> MISC_FEATURE
<222> (341)..(360)
<223> This region may encompass 6-20 residues
<220>
<221> MISC_FEATURE
<222> (367)..(371)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (375)..(379)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (383)..(387)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (391)..(395)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (399)..(403)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (407)..(411)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (415)..(419)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (423)..(427)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (364)..(427)
<223> This region may encompass 4-8 repeating "GPG-X1" repeating units,
wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some
positions may be absent
<220>
<221> MISC_FEATURE
<222> (431)..(450)
<223> This region may encompass 6-20 residues
<220>
<221> MISC_FEATURE
<222> (457)..(461)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (465)..(469)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (473)..(477)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (481)..(485)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (489)..(493)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (497)..(501)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (505)..(509)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (513)..(517)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (454)..(517)
<223> This region may encompass 4-8 repeating "GPG-X1" repeating units,
wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some
positions may be absent
<220>
<221> MISC_FEATURE
<222> (521)..(540)
<223> This region may encompass 6-20 residues
<220>
<221> MISC_FEATURE
<222> (547)..(551)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (555)..(559)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (563)..(567)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (571)..(575)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (579)..(583)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (587)..(591)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (595)..(599)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (603)..(607)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (544)..(607)
<223> This region may encompass 4-8 repeating "GPG-X1" repeating units,
wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some
positions may be absent
<220>
<221> MISC_FEATURE
<222> (611)..(630)
<223> This region may encompass 6-20 residues
<220>
<221> MISC_FEATURE
<222> (637)..(641)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (645)..(649)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (653)..(657)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (661)..(665)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (669)..(673)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (677)..(681)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (685)..(689)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (693)..(697)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (634)..(697)
<223> This region may encompass 4-8 repeating "GPG-X1" repeating units,
wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some
positions may be absent
<220>
<221> MISC_FEATURE
<222> (701)..(720)
<223> This region may encompass 6-20 residues
<220>
<221> MISC_FEATURE
<222> (727)..(731)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (735)..(739)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (743)..(747)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (751)..(755)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (759)..(763)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (767)..(771)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (775)..(779)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (783)..(787)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (724)..(787)
<223> This region may encompass 4-8 repeating "GPG-X1" repeating units,
wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some
positions may be absent
<220>
<221> MISC_FEATURE
<222> (791)..(810)
<223> This region may encompass 6-20 residues
<220>
<221> MISC_FEATURE
<222> (817)..(821)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (825)..(829)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (833)..(837)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (841)..(845)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (849)..(853)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (857)..(861)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (865)..(869)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (873)..(877)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (814)..(877)
<223> This region may encompass 4-8 repeating "GPG-X1" repeating units,
wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some
positions may be absent
<220>
<221> MISC_FEATURE
<222> (881)..(900)
<223> This region may encompass 6-20 residues
<220>
<221> MISC_FEATURE
<222> (907)..(911)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (915)..(919)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (923)..(927)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (931)..(935)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (939)..(943)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (947)..(951)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (955)..(959)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (963)..(967)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (904)..(967)
<223> This region may encompass 4-8 repeating "GPG-X1" repeating units,
wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some
positions may be absent
<220>
<221> MISC_FEATURE
<222> (971)..(990)
<223> This region may encompass 6-20 residues
<220>
<221> MISC_FEATURE
<222> (997)..(1001)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1005)..(1009)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1013)..(1017)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1021)..(1025)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1029)..(1033)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1037)..(1041)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1045)..(1049)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1053)..(1057)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (994)..(1057)
<223> This region may encompass 4-8 repeating "GPG-X1" repeating units,
wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some
positions may be absent
<220>
<221> MISC_FEATURE
<222> (1061)..(1080)
<223> This region may encompass 6-20 residues
<220>
<221> MISC_FEATURE
<222> (1087)..(1091)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1095)..(1099)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1103)..(1107)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1111)..(1115)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1119)..(1123)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1127)..(1131)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1135)..(1139)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1143)..(1147)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1084)..(1147)
<223> This region may encompass 4-8 repeating "GPG-X1" repeating units,
wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some
positions may be absent
<220>
<221> MISC_FEATURE
<222> (1151)..(1170)
<223> This region may encompass 6-20 residues
<220>
<221> MISC_FEATURE
<222> (1177)..(1181)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1185)..(1189)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1193)..(1197)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1201)..(1205)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1209)..(1213)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1217)..(1221)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1225)..(1229)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1233)..(1237)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1174)..(1237)
<223> This region may encompass 4-8 repeating "GPG-X1" repeating units,
wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some
positions may be absent
<220>
<221> MISC_FEATURE
<222> (1241)..(1260)
<223> This region may encompass 6-20 residues
<220>
<221> MISC_FEATURE
<222> (1267)..(1271)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1275)..(1279)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1283)..(1287)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1291)..(1295)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1299)..(1303)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1307)..(1311)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1315)..(1319)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1323)..(1327)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1264)..(1327)
<223> This region may encompass 4-8 repeating "GPG-X1" repeating units,
wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some
positions may be absent
<220>
<221> MISC_FEATURE
<222> (1331)..(1350)
<223> This region may encompass 6-20 residues
<220>
<221> MISC_FEATURE
<222> (1357)..(1361)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1365)..(1369)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1373)..(1377)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1381)..(1385)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1389)..(1393)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1397)..(1401)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1405)..(1409)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1413)..(1417)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1354)..(1417)
<223> This region may encompass 4-8 repeating "GPG-X1" repeating units,
wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some
positions may be absent
<220>
<221> MISC_FEATURE
<222> (1421)..(1440)
<223> This region may encompass 6-20 residues
<220>
<221> MISC_FEATURE
<222> (1447)..(1451)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1455)..(1459)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1463)..(1467)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1471)..(1475)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1479)..(1483)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1487)..(1491)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1495)..(1499)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1503)..(1507)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1444)..(1507)
<223> This region may encompass 4-8 repeating "GPG-X1" repeating units,
wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some
positions may be absent
<220>
<221> MISC_FEATURE
<222> (1511)..(1530)
<223> This region may encompass 6-20 residues
<220>
<221> MISC_FEATURE
<222> (1537)..(1541)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1545)..(1549)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1553)..(1557)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1561)..(1565)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1569)..(1573)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1577)..(1581)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1585)..(1589)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1593)..(1597)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1534)..(1597)
<223> This region may encompass 4-8 repeating "GPG-X1" repeating units,
wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some
positions may be absent
<220>
<221> MISC_FEATURE
<222> (1601)..(1620)
<223> This region may encompass 6-20 residues
<220>
<221> MISC_FEATURE
<222> (1627)..(1631)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1635)..(1639)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1643)..(1647)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1651)..(1655)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1659)..(1663)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1667)..(1671)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1675)..(1679)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1683)..(1687)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1624)..(1687)
<223> This region may encompass 4-8 repeating "GPG-X1" repeating units,
wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some
positions may be absent
<220>
<221> MISC_FEATURE
<222> (1691)..(1710)
<223> This region may encompass 6-20 residues
<220>
<221> MISC_FEATURE
<222> (1717)..(1721)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1725)..(1729)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1733)..(1737)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1741)..(1745)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1749)..(1753)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1757)..(1761)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1765)..(1769)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1773)..(1777)
<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or
"SQ," wherein some positions may be absent
<220>
<221> MISC_FEATURE
<222> (1714)..(1777)
<223> This region may encompass 4-8 repeating "GPG-X1" repeating units,
wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some
positions may be absent
<220>
<221> MISC_FEATURE
<222> (1781)..(1800)
<223> This region may encompass 6-20 residues
<220>
<221> MISC_FEATURE
<222> (1)..(1800)
<223> This sequence may encompass 2-20 "GGY-[GPG-X1]n1-GPS-(A)n2"
repeating units, wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ"
or "SQ," n1 is 4-8 and n2 is 6-20 and some positions may be
absent
<400> 149
Gly Gly Tyr Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa
1 5 10 15
Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa
20 25 30
Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa
35 40 45
Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa
50 55 60
Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
65 70 75 80
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly
85 90 95
Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly
100 105 110
Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly
115 120 125
Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly
130 135 140
Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Ser
145 150 155 160
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
165 170 175
Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly
180 185 190
Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly
195 200 205
Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly
210 215 220
Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly
225 230 235 240
Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala
245 250 255
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly
260 265 270
Tyr Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa
275 280 285
Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa
290 295 300
Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa
305 310 315 320
Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa
325 330 335
Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
340 345 350
Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Xaa Xaa
355 360 365
Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa
370 375 380
Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa
385 390 395 400
Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa
405 410 415
Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala
420 425 430
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
435 440 445
Ala Ala Gly Gly Tyr Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly
450 455 460
Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly
465 470 475 480
Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly
485 490 495
Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly
500 505 510
Xaa Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala
515 520 525
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly
530 535 540
Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly
545 550 555 560
Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly
565 570 575
Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly
580 585 590
Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly
595 600 605
Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
610 615 620
Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Xaa Xaa Xaa Xaa
625 630 635 640
Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa
645 650 655
Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa
660 665 670
Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa
675 680 685
Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala
690 695 700
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
705 710 715 720
Gly Gly Tyr Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa
725 730 735
Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa
740 745 750
Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa
755 760 765
Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa
770 775 780
Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
785 790 795 800
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly
805 810 815
Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly
820 825 830
Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly
835 840 845
Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly
850 855 860
Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Ser
865 870 875 880
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
885 890 895
Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly
900 905 910
Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly
915 920 925
Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly
930 935 940
Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly
945 950 955 960
Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala
965 970 975
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly
980 985 990
Tyr Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa
995 1000 1005
Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa
1010 1015 1020
Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa
1025 1030 1035 1040
Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa
1045 1050 1055
Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
1060 1065 1070
Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Xaa Xaa
1075 1080 1085
Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa
1090 1095 1100
Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa
1105 1110 1115 1120
Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa
1125 1130 1135
Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala
1140 1145 1150
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
1155 1160 1165
Ala Ala Gly Gly Tyr Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly
1170 1175 1180
Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly
1185 1190 1195 1200
Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly
1205 1210 1215
Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly
1220 1225 1230
Xaa Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala
1235 1240 1245
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly
1250 1255 1260
Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly
1265 1270 1275 1280
Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly
1285 1290 1295
Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly
1300 1305 1310
Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly
1315 1320 1325
Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
1330 1335 1340
Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Xaa Xaa Xaa Xaa
1345 1350 1355 1360
Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa
1365 1370 1375
Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa
1380 1385 1390
Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa
1395 1400 1405
Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala
1410 1415 1420
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
1425 1430 1435 1440
Gly Gly Tyr Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa
1445 1450 1455
Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa
1460 1465 1470
Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa
1475 1480 1485
Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa
1490 1495 1500
Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
1505 1510 1515 1520
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly
1525 1530 1535
Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly
1540 1545 1550
Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly
1555 1560 1565
Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly
1570 1575 1580
Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Ser
1585 1590 1595 1600
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
1605 1610 1615
Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly
1620 1625 1630
Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly
1635 1640 1645
Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly
1650 1655 1660
Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly
1665 1670 1675 1680
Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala
1685 1690 1695
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly
1700 1705 1710
Tyr Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa
1715 1720 1725
Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa
1730 1735 1740
Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa
1745 1750 1755 1760
Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa
1765 1770 1775
Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
1780 1785 1790
Ala Ala Ala Ala Ala Ala Ala Ala
1795 1800
<210> 150
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic peptide
<400> 150
Ser Gly Gly Gln Gln
1 5
<210> 151
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic peptide
<400> 151
Gly Ala Gly Gln Gln
1 5
<210> 152
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic peptide
<400> 152
Gly Gln Gly Pro Tyr
1 5
<210> 153
<211> 4
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic peptide
<400> 153
Ala Gly Gln Gln
1
<210> 154
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic peptide
<220>
<221> MISC_FEATURE
<222> (1)..(8)
<223> This sequence may encompass 6-8 residues
<400> 154
His His His His His His His His
1 5
Claims (32)
- 재조합 분비 신호에 작동가능하게 연결된 실크 또는 실크 유사 단백질을 암호화하는 폴리뉴클레오타이드 서열을 포함하되,
상기 재조합 분비 신호는 리더 펩타이드와 신호 펩타이드를 포함하고,
상기 리더 펩타이드가 서열번호 1 또는 서열번호 2의 아미노산 서열을 포함하고,
상기 신호 펩타이드는 프리-αMF(sc)를 포함하지 않는, 발현 작제물.
- 제1항에 있어서,
상기 리더 펩타이드는 서열번호 2의 아미노산 서열을 포함하고,
상기 신호 펩타이드는 서열번호 9의 아미노산 서열을 포함하는, 발현 작제물.
- 제1항에 있어서,
상기 신호 펩타이드는 서열번호 3 내지 9 및 116 내지 129로 구성된 군에서 선택된 아미노산 서열을 포함하는, 발현 작제물.
- 제1항에 있어서,
상기 재조합 분비 신호는 서열번호 10 내지 16 및 130 내지 143로 구성된 군에서 선택된 아미노산 서열을 포함하는, 발현 작제물.
- 제1항에 있어서,
상기 폴리뉴클레오타이드 서열은 다중 카피로 존재하는, 발현 작제물.
- 제1항에 있어서,
상기 폴리뉴클레오타이드 서열은 프로모터에 작동가능하게 연결되는, 발현 작제물.
- 제6항에 있어서,
상기 프로모터는 피키아 파스토리스의 pGCW14 프로모터이거나;
상기 프로모터는 피키아 파스토리스의 pGAP 프로모터이거나; 또는
상기 프로모터는 유도성 프로모터인, 발현 작제물.
- 제1항에 있어서,
상기 실크 또는 실크 유사 단백질은 서열번호 17 또는 서열번호 17의 다중 카피를 포함하는, 발현 작제물.
- 재조합 벡터로서,
상기 벡터는 제1항 내지 제8항 중 어느 한 항의 발현 작제물을 포함하거나; 또는
상기 벡터는 제1항 내지 제8항 중 어느 한 항의 발현 작제물을 포함하고,
상기 발현 작제물은 다중 카피로 존재하거나, 또는
상기 벡터는 PARS를 포함하는, 재조합 벡터.
- 제1항 내지 제8항 중 어느 한 항의 발현 작제물을 포함하는, 재조합 숙주 세포.
- 제10항에 있어서,
상기 재조합 숙주 세포는 효모 세포이거나; 또는
상기 재조합 숙주 세포는 출아(budding) 효모 세포 또는 메탄올자화성 효모 세포인, 재조합 숙주 세포.
- 제11항에 있어서,
상기 재조합 숙주 세포가 피키아 (Pichia) 종 이거나, 또는 피키아 파스토리스인, 재조합 숙주 세포.
- 제10항에 있어서,
상기 발현 작제물은 상기 재조합 숙주 세포의 게놈 내에 안정적으로 통합되거나;
상기 발현 작제물은 상기 재조합 숙주 세포에서 염색체 외적으로 유지되거나; 또는
상기 재조합 숙주 세포는 상기 재조합 숙주 세포에 의해 생산된 상기 실크 또는 실크 유사 단백질의 총 수율의 적어도 30 중량%의 상기 발현 작제물에 포함된 상기 폴리뉴클레오타이드 서열에 의해 암호화되는 상기 실크 또는 실크 유사 단백질의 분비 수율을 생산하는, 재조합 숙주 세포.
- 발효물로서,
상기 발효물은 제10항의 재조합 숙주 세포 및 배양 배지를 포함하거나; 또는
상기 발효물은 제10항의 재조합 숙주 세포 및 배양 배지를 포함하고,
상기 발효물은 분비된 단백질로서 상기 재조합 숙주 세포에 의해 생산된 상기 발현 작제물에 포함된 상기 폴리뉴클레오타이드 서열에 의해 암호화되는 상기 실크 또는 실크 유사 단백질의 총 수율의 적어도 30 중량%을 포함하거나, 또는
상기 발효물의 상기 배양 배지는 상기 발현 작제물에 포함된 상기 폴리뉴클레오타이드 서열에 의해 암호화되는 상기 실크 또는 실크 유사 단백질의 적어도 0.5 g/L을 포함하는, 발효물.
- 단백질을 생산하기 위한 방법으로서,
a) 배양 배지 중에서 제10항의 재조합 숙주 세포를 배양하여 상기 재조합 숙주 세포 및 상기 배양 배지를 포함하는 발효물을 수득하는 단계; 및
b) 상기 실크 또는 실크 유사 단백질을 상기 배양 배지로부터 추출하는 단계를 포함하는, 방법. - 삭제
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PCT/US2018/021812 WO2018165589A2 (en) | 2017-03-10 | 2018-03-09 | Compositions and methods for producing high secreted yields of recombinant proteins |
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KR20240071112A (ko) | 2022-11-15 | 2024-05-22 | 숙명여자대학교산학협력단 | 사료용 미생물단백질 생산을 위한 신규한 사카로마이세스 세레비지에 균주 |
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US11725030B2 (en) | 2023-08-15 |
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