KR20200058482A - 재조합 실크 제조를 위한 변형 균주 - Google Patents
재조합 실크 제조를 위한 변형 균주 Download PDFInfo
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Abstract
본 발명은 숙주 유기체로부터 분비되는 재조합 발현 생성물의 분해를 감소시키는 변형된 균주 및 이러한 변형된 균주의 사용 방법을 개시한다.
Description
발명의 분야
본 발명은 세포로부터 단백질 또는 대사산물의 생성을 생성 또는 향상시키기 위한 균주 최적화 방법에 관한 것이다. 본 발명은 또한 이들 방법으로부터 생성된 조성물에 관한 것이다. 특히, 본 발명은 효모 세포에 의해 발현된 재조합 단백질의 분해를 감소시키도록 선택되거나 유전자 조작된 효모 세포, 및 유용한 화합물의 제조를 위해 효모 세포를 배양하는 방법에 관한 것이다.
메탄올자화 효모 피키아 파스토리스 (Pichia pastoris)는 재조합 단백질의 제조에 널리 사용된다. P. 파스토리스는높은 세포 밀도로 성장하고, 엄격하게 제어된 메탄올-유도성 트랜스 유전자 발현을 제공하고, 한정된 배지에서 이종 단백질을 효과적으로 분비한다.
그러나, P. 파스토리스 균주의 배양 동안, 재조합 발현 단백질은 수집되기 전에 분해될 수 있어, 재조합 발현 단백질의 단편 및 감소된 수율의 전장 재조합 단백질을 포함하는 단백질의 혼합물을 생성할 수 있다. 따라서, P. 파스토리스에서 단백질 분해를 완화시키기 위한 도구 및 조작된 균주가 필요하다.
발명의 요약
일부 구체예에서, 본 발명은 YPS1-1 프로테아제 및 YPS1-2 프로테아제의 활성이 약화되거나 제거된 피키아 파스토리스 미생물을 제공하며, 여기서 상기 미생물은 재조합 폴리펩티드를 발현한다.
일부 구체예에서, YPS1-1 프로테아제는 서열 번호: 67에 최소한 95% 동일한 폴리펩티드 서열을 포함한다. 일부 구체예들에서, YPS1-1 프로테아제는 서열 번호: 67을 포함한다. 일부 구체예들에서, YPS1-1 프로테아제는 YPS1-1 유전자에 의해 인코드된다. 일부 구체예들에서, YPS1-1 유전자는 서열 번호: 1에 최소한 95% 동일한 폴리뉴클레오티드 서열을 포함한다. 일부 구체예들에서, YPS1-1 유전자는 서열 번호: 1의 15, 20, 25, 30, 40, 또는 50개 이상의 인접 뉴클레오티드를 포함한다. 일부 구체예들에서, YPS1-1 유전자는 서열 번호: 1을 포함한다. 일부 구체예들에서, YPS1-1 유전자는 상기 미생물의 PAS_chr4_0584 좌위에 존재한다.
일부 구체예에서, YPS1-2 프로테아제는 서열 번호: 68에 최소한 95% 동일한 폴리펩티드 서열을 포함한다. 일부 구체예들에서, YPS1-2 프로테아제는 서열 번호: 68을 포함한다. 일부 구체예들에서, YPS1-2 프로테아제는 YPS1-2 유전자에 의해 인코드된다. 일부 구체예들에서, YPS1-2 유전자는 서열 번호: 2에 최소한 95% 동일한 폴리뉴클레오티드 서열을 포함한다. 일부 구체예들에서, YPS1-2 유전자는 서열 번호: 2의 15, 20, 25, 30, 40, 또는 50개 이상의 인접 뉴클레오티드를 포함한다. 일부 구체예들에서, YPS1-2 유전자는 서열 번호: 2를 포함한다. 일부 구체예들에서, YPS1-2 유전자는 상기 미생물의 PAS_chr3_1157 좌위에 존재한다.
일부 구체예들에서, YPS1-1 유전자 또는 상기 YPS1-2 유전자, 또는 둘 모두는 돌연변이되었거나 녹아웃되었다.
일부 구체예들에서, 미생물은 재조합 단백질을 발현한다. 일부 구체예들에서, 재조합 단백질은 실크 단백질로부터의 하나 이상의 블록 폴리펩티드 서열을 포함한다. 일부 구체예들에서, 재조합 단백질은 실크 유사 폴리펩티드를 포함한다. 일부 구체예들에서, 실크-유사 폴리펩티드는 하나 이상의 반복 서열들 {GGY-[GPG-X1]n1-GPS-(A)n2}n3 (서열 번호: 514)을 포함하고, 이 때 X1 = SGGQQ (서열 번호: 515) 또는 GAGQQ (서열 번호: 516) 또는 GQGPY (서열 번호: 517) 또는 AGQQ (서열 번호: 518) 또는 SQ이고; n1은 4 내지 8이고; n2는 6 내지 20이고; 그리고 n3는 2 내지 20이다. 일부 구체예들에서, 실크-유사 폴리펩티드는 서열 번호: 462에 의해 인코드되는 폴리펩티드 서열을 포함한다.
일부 구체예들에서, 미생물에서 하나 이상의 추가 프로테아제들의 활성은 약화되었거나 제거되었다. 일부 구체예들에서, 하나 이상의 추가 프로테아제는 YPS1-5, MCK7, 또는 YPS1-3을 포함한다.
일부 구체예들에서, YPS1-5 유전자는 상기 미생물의 PAS_chr3_0688 좌위에 존재한다.
일부 구체예들에서, MCK7 프로테아제는 서열 번호: 7에 최소한 95% 동일한 폴리뉴클레오티드 서열을 포함하는 MCK7 유전자에 의해 인코드된다. 일부 구체예들에서, MCK7 유전자는 서열 번호: 7의 15, 20, 25, 30, 40, 또는 50개 이상의 인접 뉴클레오티드를 포함한다. 일부 구체예들에서, MCK7 유전자는 서열 번호: 7을 포함한다. 일부 구체예들에서, MCK7 유전자는 상기 미생물의 PAS_chr1-1_0379 좌위에 존재한다.
일부 구체예들에서, YPS1-3 프로테아제는 서열 번호: 3에 최소한 95% 동일한 폴리뉴클레오티드 서열을 포함하는 YPS1-3 유전자에 의해 인코드된다. 일부 구체예들에서, YPS1-3 유전자는 서열 번호: 3의 15, 20, 25, 30, 40, 또는 50개 이상의 인접 뉴클레오티드를 포함한다. 일부 구체예들에서, YPS1-3 유전자는 서열 번호: 3을 포함한다. 일부 구체예들에서, YPS1-3 유전자는 상기 미생물의 PAS_chr3_0299 좌위에 존재한다.
일부 구체예들에서, 하나 이상의 추가 프로테아제는 서열 번호: 68 - 130으로 구성된 그룹에서 선택된 폴리펩티드 서열에 최소한 95% 동일한 폴리펩티드 서열을 포함한다. 일부 구체예들에서, 하나 이상의 추가 프로테아제는 서열 번호: 68 - 130으로 구성된 그룹에서 선택된 폴리펩티드 서열을 포함한다. 일부 구체예들에서, 하나 이상의 추가 프로테아제는 서열 번호: 3 - 66으로 구성된 그룹에서 선택된 폴리뉴클레오티드 서열에 최소한 95% 동일한 폴리뉴클레오티드 서열에 의해 인코드된다. 일부 구체예들에서, 하나 이상의 추가 프로테아제는 서열 번호: 3 - 66으로 구성된 그룹에서 선택된 폴리뉴클레오티드 서열의 15, 20, 25, 30, 40, 또는 50개 이상의 인접 뉴클레오티드를 포함하는 뉴클레오티드 서열에 의해 인코드된다.
일부 구체예들에서, 미생물은 3X, 4X 또는 5X 프로테아제 녹아웃을 포함한다.
또한 본 발명은, 본 발명의 일부 구체예들에 따르면, 서열 번호: 1을 포함하는 YPS1-1 유전자 및 서열 번호: 2를 포함하는 YPS1-2 유전자의 돌연변이 또는 결실에 의해 감소되는 YPS1-1 및 YPS1-2 활성을 포함하는 조작된 미생물 피키아 파스토리스를 제공하며, 이 때 상기 미생물은 서열 번호: 462에 의해 인코드되는 폴리펩티드 서열을 포함하는 재조합 발현 단백질을 추가로 포함한다.
일부 구체예들에서, 또한 본 발명은 본 명세서에 기재된 프로테아제 완화 미생물을 포함하는 세포 배양물을 제공한다.
또한, 일부 구체예에 따르면, 본 명세서에 기재된 YPS1-1 및 YPS1-2 활성이 약화되거나 제거된 미생물을 포함하는 세포 배양물을 제공하며, 여기서 미생물은 단백질을 재조합적으로 발현하고, 상기 재조합적으로 발현된 단백질은 YPS1-1 및 YPS1-2 활성이 약화되거나 제거되지 않은 그 외 동일한 피키아 파스토리스 미생물을 포함하는 세포 배양물보다 덜 분해된다.
일부 구체예들에서, 본 발명은 다음 단계를 포함하는, 분해가 감소된 재조합 단백질의 제조 방법을 제공한다: YPS1-1 및 YPS1-2 활성이 재조합 발현 단백질의 발현에 적합한 조건하의 배양 배지에서 본 명세서에 기재된 바와 같이 약화되었거나 제거된 미생물을 배양하는 단계; 및 미생물 또는 배양 배지로부터 재조합 단백질을 단리하는 단계.
일부 구체예들에서, 재조합 단백질은 상기 미생물로부터 분비되며, 상기 재조합 단백질을 단리하는 단계는 상기 분비된 재조합 단백질을 포함하는 배양 배지를 수집하는 단계를 포함한다. 일부 구체예들에서, 재조합 단백질은 다른 동일한 미생물에 의해 생성된 상기 재조합 단백질과 비교하여 감소된 수준의 분해를 가지며, 여기서 상기 YPS1-1 및 상기 YPS1-2 프로테아제 활성은 약화되거나 제거되지 않았다.
또한, 본 발명은 YPS1-1 단백질 및 YPS1-2 단백질을 인코드하는 유전자를 녹아웃 또는 돌연변이시키는 단계를 포함하는, 재조합 발현된 단백질의 분해를 감소시키기 위해 피키아 파스토리스를 변형시키는 방법을 제공한다. 일부 구체예들에서, 재조합 발현 단백질의 분해를 감소시키기 위해 피키아 파스토리스를 변형시키는 방법은 YPS1-3 단백질, YPS1-5 단백질 또는 MCK7 단백질을 코딩하는 하나 이상의 추가 유전자를 녹아웃 또는 돌연변이시키는 단계를 추가로 포함한다. 일부 구체예들에서, 재조합 발현 단백질의 분해를 감소시키기 위해 피키아 파스토리스를 변형시키는 방법은 서열 번호: 68-130으로 구성된 그룹에서 선택된 폴리펩티드를 포함하는 단백질을 인코드하는 하나 이상의 유전자를 녹아웃시키는 단계를 추가로 포함한다.
일부 구체예들에서, 재조합 발현 단백질은 2, 3, 4, 5, 6, 7, 8, 9, 또는 10개 이상의 인접 알라닌 잔기들을 포함하는 폴리A 서열을 포함한다. 일부 구체예들에서, 재조합 발현 단백질은 실크-유사 폴리펩티드를 포함한다. 일부 구체예들에서, 실크-유사 폴리펩티드는 하나 이상의 반복 서열들 {GGY-[GPG-X1]n1-GPS-(A)n2}n3(서열 번호: 514)을 포함하고, 이 때 X1 = SGGQQ (서열 번호: 515) 또는 GAGQQ (서열 번호: 516) 또는 GQGPY (서열 번호: 517) 또는 AGQQ (서열 번호: 518) 또는 SQ이고; n1은 4 내지 8이고; n2는 6 내지 20이고; 그리고 n3는 2 내지 20이다. 일부 구체예들에서, 재조합 발현 단백질은 서열 번호: 462에 의해 인코드되는 폴리펩티드 서열을 포함한다.
도면의 간단한 설명
전술한 그리고 다른 목적, 특징 및 이점들은 첨부된 도면에 도시된 바와 같은 본 발명의 특정 구체예들에 관한 하기 설명으로부터 명백해질 것이며, 도면에서 유사한 도면 부호는 서로 다른 도면 전반에 걸쳐 동일한 부분을 지칭한다. 도면은 반드시 축척대로 도시된 것은 아니며, 대신 본 발명의 다양한 구체예의 원리를 설명하기 위해 강조된다.
도 1은 제오신 내성 마커를 사용한, KU 70 결실에 대한 플라스미드 맵이다.
도 2는 표적화된 프로테아제 유전자 결실을 위해 상동성 아암과 함께 사용되는 노르세오트리신 마커를 포함하는 플라스미드의 플라스미드 맵이다.
도 3A 및 도 3B는 노르세오트리신 내성 마커에 연접하여, 원하는 프로테아제 유전자를 표적하는 상동성 아암을 가지는, 프로테아제 녹아웃을 위한 카세트이다.
도 4는 단일 KO 균주들로부터 단리된 단백질의 대표적인 웨스턴 블롯으로, 이들 균주로부터의 단백질 분해를 보여준다.
도 5는 이중 KO 균주들로부터 단리된 단백질의 대표적인 웨스턴 블롯으로, 이들 균주로부터의 단백질 분해를 보여준다.
도 6은 BMGY 또는 YPD에서 계대배양된 2X, 3X, 4X, 및 5X 프로테아제 KO 균주들로부터 단리된 단백질의 대표적인 웨스턴 블롯으로, 이들 균주로부터의 단백질 분해를 보여준다.
전술한 그리고 다른 목적, 특징 및 이점들은 첨부된 도면에 도시된 바와 같은 본 발명의 특정 구체예들에 관한 하기 설명으로부터 명백해질 것이며, 도면에서 유사한 도면 부호는 서로 다른 도면 전반에 걸쳐 동일한 부분을 지칭한다. 도면은 반드시 축척대로 도시된 것은 아니며, 대신 본 발명의 다양한 구체예의 원리를 설명하기 위해 강조된다.
도 1은 제오신 내성 마커를 사용한, KU 70 결실에 대한 플라스미드 맵이다.
도 2는 표적화된 프로테아제 유전자 결실을 위해 상동성 아암과 함께 사용되는 노르세오트리신 마커를 포함하는 플라스미드의 플라스미드 맵이다.
도 3A 및 도 3B는 노르세오트리신 내성 마커에 연접하여, 원하는 프로테아제 유전자를 표적하는 상동성 아암을 가지는, 프로테아제 녹아웃을 위한 카세트이다.
도 4는 단일 KO 균주들로부터 단리된 단백질의 대표적인 웨스턴 블롯으로, 이들 균주로부터의 단백질 분해를 보여준다.
도 5는 이중 KO 균주들로부터 단리된 단백질의 대표적인 웨스턴 블롯으로, 이들 균주로부터의 단백질 분해를 보여준다.
도 6은 BMGY 또는 YPD에서 계대배양된 2X, 3X, 4X, 및 5X 프로테아제 KO 균주들로부터 단리된 단백질의 대표적인 웨스턴 블롯으로, 이들 균주로부터의 단백질 분해를 보여준다.
상세한 설명
본 발명의 다양한 구체예들에 관한 세부사항은 하기 상세한 설명에서 설명된다. 본 발명의 그 외 다른 특징, 목적 및 이점들은 하기 상세한 설명과 도면 및 청구범위로부터 명확해 질 것이다.
정의
본 명세서에 달리 정의되지 않는 한, 본 발명과 관련하여 사용되는 과학 및 기술 용어들은 해당 분야의 숙련된 기술자들이 통상적으로 이해하는 의미를 가져야 한다. 더욱이, 내용에서 달리 필요하지 않는 한, 단수형 용어들은 복수형을 포함하며, 복수형 용어들은 단수형을 포함한다. 용어 "하나 (a 및 an)"는 내용에서 달리 언급이 없는 한 복수의 지칭을 포함한다. 일반적으로, 본 발명에 기술된 생화학, 효소학, 분자 및 세포 생물학, 미생물학, 유전학 및 단백질과 핵산 화학 및 혼성화와 관련하여 사용되는 명명법 및 이의 기술들은 해당 분야에 잘 알려져 있고 통상적으로 사용되는 것들이다.
달리 언급이 없는 한, 하기 용어들은 다음과 같은 의미를 가지는 것으로 이해되어야 한다:
용어 "폴리뉴클레오티드" 또는 "핵산 분자"는 최소한 10개 염기 길이의 뉴클레오티드의 폴리머 형태를 지칭한다. 상기 용어는 DNA 분자 (예를 들어, cDNA 또는 게놈 또는 합성 DNA) 및 RNA 분자 (예를 들어, mRNA 또는 합성 RNA)뿐만 아니라 비-천연 뉴클레오티드 유사체, 비-고유 뉴클레오시드간 결합, 또는 둘 모두를 포함하는 DNA 또는 RNA의 유사체를 포함한다. 핵산은 임의의 토폴로지 입체형태일 수 있다. 예를 들면, 핵산은 단일 가닥, 이중 가닥, 삼중 가닥, 4중 가닥, 부분 이중 가닥, 분지형, 헤어핀, 원형 또는 자물쇠 입체형태 일 수 있다.
달리 지시되지 않는 한, 및 일반적인 형식 "서열 번호:"로 본 명세서에 기재된 모든 서열에 대한 예로서, "서열 번호: 1을 포함하는 핵산"은 최소한 일부가 (i) 서열 번호: 1의 서열, 또는 (ii) 서열 번호: 1에 상보적인 서열을 가짐을 지칭한다. 둘 중 선택은 내용에 따라 결정된다. 예를 들어, 핵산이 프로브로 사용되는 경우, 둘 중 하나의 선택은 프로브가 원하는 표적에 상보적이어야한다는 요건에 의해 결정된다.
"단리된" RNA, DNA 또는 혼합 중합체는 천연 숙주 세포에서 고유 폴리뉴클레오티드와 자연적으로 수반되는 다른 세포 성분들, 예를 들어, 리보솜, 폴리머라제 및 자연적으로 관련된 게놈 서열로부터 실질적으로 분리된 것이다.
"단리된" 유기 분자 (예를 들어, 실크 단백질)는 그것이 유래된 숙주 세포의 세포 성분 (막 지질, 염색체, 단백질) 또는 숙주 세포가 배양되었던 배지로부터 실질적으로 분리된 것이다. 특정한 단리된 생체 분자는 거의 균질하게 정제될 수 있지만, 이 용어는 생체 분자가 다른 모든 화학 물질로부터 분리될 것을 요구하지는 않는다.
용어 "재조합"은 (1) 자연 발생 환경으로부터 제거되어 있거나, (2) 유전자가 자연에서 발견되는 폴리뉴클레오티드의 전부 또는 일부와 연관되어 있지 않거나, (3) 자연에서는 연결되지 않은 폴리뉴클레오티드에 작동가능하게 연결되거나, 또는 (4) 실제로는 발생하지 않는, 생체 분자, 예를 들어, 유전자 또는 단백질을 의미한다. 용어 "재조합"은 클로닝된 DNA 단리물, 화학적으로 합성된 폴리뉴클레오티드 유사체, 또는 이종시스템에 의해 생물학적으로 합성된 폴리뉴클레오티드 유사체뿐만 아니라 이러한 핵산에 의해 인코드된 단백질 및/또는 mRNA와 관련하여 사용될 수 있다.
이종 서열이 유기체 게놈 내 내인성 핵산 서열 (또는 이러한 서열의 인코드된 단백질 생성물)에 인접하여 배치되어, 이러한 내인성 핵산 서열의 발현이 변형되는 경우, 이러한 내인성 핵산 서열은 "재조합"으로 간주된다. 이와 관련하여, 이종 서열은 이종 서열 자체가 내인성인지 (동일한 숙주 세포 또는 이의 자손에서 유래한 것인지) 또는 외인성인지 (다른 숙주 세포 또는 이의 자손에서 유래한 것인지)에 관계없이 내인성 핵산 서열에 자연적으로 인접하지 않는 서열이다. 예를 들어, 프로모터 서열은 숙주 세포의 게놈 내 유전자의 고유 프로모터로 대체 될 수 있고 (예를 들어, 상동 재조합에 의해), 그 결과 이 유전자는 변경된 발현 패턴을 가진다. 이 유전자는 자연적으로 연접하는 서열들 중 최소한 일부로부터 분리되기 때문에 이제 "재조합"이 될 것이다.
핵산은 또한 게놈 내 상응하는 핵산에서 자연적으로 발생하지 않는 임의의 변형을 함유하는 경우 "재조합"으로 간주된다. 예를 들어, 내인성 코딩 서열은, 예를 들어, 인간의 개입에 의해 인공적으로 도입 된 삽입, 결실 또는 점 돌연변이를 함유하는 경우 "재조합"으로 간주된다. "재조합 핵산"은 또한 이종 부위에서 숙주 세포 염색체에 통합된 핵산 및 에피 솜으로 존재하는 핵산 구조체를 포함한다.
본 명세서에서 사용되는, 참조 핵산 서열에 관한 어구 "축퇴 변이체"는 표준 유전자 코드에 따라 번역되어 참조 핵산 서열로부터 번역된 것과 동일한 아미노산 서열을 제공 할 수 있는 핵산 서열을 포함한다. 용어 "축퇴 올리고뉴클레오티드" 또는 "축퇴 프라이머"는 서열이 반드시 동일하지는 않지만 하나 이상의 특정 분절 내에서 서로 상동인 표적 핵산 서열과 혼성화 할 수 있는 올리고뉴클레오티드를 나타내기 위해 사용된다.
핵산 서열과 관련하여 용어 "서열 동일성 퍼센트" 또는 "동일한"은 최대 상응을 위해 정렬될 때 동일한 두 개의 서열 내 잔기들을 지칭한다. 서열 동일성 비교의 길이는 약 9개 이상의 뉴클레오티드, 일반적으로 약 20개 이상의 뉴클레오티드, 보다 일반적으로 약 24개 이상의 뉴클레오티드, 전형적으로 약 28개 이상의 뉴클레오티드, 보다 전형적으로 약 32개 이상의 뉴클레오티드, 및 바람직하게는 약 36개 이상의 뉴클레오티드의 스트레치에 걸친 것일 수 있다. 뉴클레오티드 서열 동일성을 측정하는데 사용될 수 있는 해당 분야에 공지된 다수의 상이한 알고리즘이 존재한다. 예를 들어, 폴리뉴클레오티드 서열은 위스콘신주, 메디슨의 Genetics Computer Group (GCG)사 Wisconsin Package Version 10.0의 프로그램인 FASTA, Gap 또는 Bestfit을 사용하여 비교 될 수 있다. FASTA는 문제(query) 서열과 검색 서열간의 가장 잘 겹쳐지는 영역의 정렬 및 서열 동일성 퍼센트를 제공한다. Pearson, Methods Enzymol. 183:63-98 (1990) (본 명세서에 그 전문이 참고문헌으로 포함됨). 예를 들어, 핵산 서열들 사이의 서열 동일성 퍼센트는 기본 파라미터 (점수화 행렬에 대한 NOPAM 인자 및 워드 크기 6)의 FASTA를 사용하거나 본 명세서에 참고로 포함된 GCG 버전 6.1에 제공된 바와 같은 기본 파라미터를 가지는 갭을 사용하여 결정될 수 있다. 대안적으로, 서열들은 컴퓨터 프로그램, BLAST를 사용하여 비교될 수 있다 (Altschul 외, J. Mol. Biol. 215:403-410 (1990); Gish and States, Nature Genet. 3:266-272 (1993); Madden 외, Meth. Enzymol. 266:131-141 (1996); Altschul 외, Nucleic Acids Res. 25:3389-3402 (1997); Zhang and Madden, Genome Res. 7:649-656 (1997)), 특히 blastp 또는 tblastn (Altschul 외, Nucleic Acids Res. 25:3389-3402 (1997)).
핵산 또는 이의 단편을 지칭할 때 용어 "실질적 상동성" 또는 "실질적 유사성"은, 상기 논의한 FASTA, BLAST 또는 Gap과 같은 임의의 공지된 서열 동일성 알고리즘으로 측정시, 적절한 뉴클레오티드 삽입 또는 결실과 함께 또 다른 핵산 (또는 이의 상보적 가닥)과 최적으로 정렬될 경우, 최소한 약 75%, 80%, 85%, 바람직하게는 최소한 약 90%, 그리고 더욱 바람직하게는 최소한 약 95%, 96%, 97%, 98% 또는 99%의 뉴클레오티드 염기에서 뉴클레오티드 서열 동일성이 존재함을 의미한다.
대안적으로, 엄격한 혼성화 조건하에서 핵산 또는 이의 단편이 다른 핵산, 다른 핵산의 가닥 또는 이의 상보적 가닥에 혼성화 될 때 실질적인 상동성 또는 유사성이 존재한다. 핵산 혼성화 실험과 관련하여 "엄격한 혼성화 조건"및 "엄격한 세척 조건"은 다수의 상이한 물리적 파라미터에 의존한다. 핵산 혼성화는 염 농도, 온도, 용매, 혼성화 종의 기본 조성, 상보적 영역의 길이 및 혼성화 핵산 사이의 뉴클레오티드 염기 미스매치수와 같은 조건에 의해 영향을 받을 것이며, 이는 해당 분야의 숙련된 기술자에게 용이하게 이해될 것이다. 해당 분야의 숙련된 기술자는 특정한 혼성화 엄격성을 달성하기 위해 이들 파라미터를 변화시키는 방법을 알고 있다.
일반적으로, "엄격한 혼성화"는 특정 세트의 조건하에서 특정 DNA 하이브리드에 대한 열 용융점 (Tm) 미만인 약 25°C에서 실시된다. "엄격한 세척"은 특정 세트의 조건하에서 특정 DNA 하이브리드에 대해 Tm보다 약 5 ℃낮은 온도에서 실시된다. Tm은 표적 서열의 50%가 완전하게 매칭된 프로브에 혼성화하는 온도이다. Sambrook 외, Molecular Cloning: A Laboratory Manual, 2d ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (1989), 페이지 9.51, 본 명세서에 참고문헌으로 포함됨. 본 명세서의 목적과 관련하여, "엄격한 조건"은 용액상 혼성화에 대해 6xSSC (여기서 20xSSC는 3.0 M NaCl 및 0.3 M 소듐 시트레이트를 함유함)에서의 수성 혼성화 (즉, 포름아마이드가 없음), 65℃에서 8-12 시간 동안 1% SDS, 후속하여 0.2xSSC에서 2회 세척, 65℃에서 20분 동안 0.1% SDS로서 정의된다. 숙련된 기술자는 65℃에서의 혼성화가 혼성화하는 서열의 길이 및 퍼센트 동일성을 포함한 다수의 인자에 따라 상이한 비율로 발생하게 됨을 이해할 것이다.
본 발명의 핵산 (폴리뉴클레오티드로도 지칭됨)은 RNA, cDNA, 게놈 DNA, 및 상기의 합성 형태 및 혼합 중합체의 센스 및 안티센스 가닥 둘 모두를 포함할 수 있다. 이들은 화학적으로 또는 생화학적으로 변형 될 수 있거나, 비-천연 또는 유도체화 된 뉴클레오티드 염기를 함유 할 수 있으며, 이를 해당 분야의 숙련된 기술자는 쉽게 이해할 것이다. 이러한 변형들에는, 예를 들면, 표지화, 메틸화, 하나 이상의 자연 발생 뉴클레오티드의 유사체로의 치환, 뉴클레오티드간 변형, 가령, 비하전된 링키지 (예컨대, 메틸 포스포네이트, 포스포트라이에스터, 포스포라미데이트, 카바메이트, 등), 하전된 링키지 (예컨대, 포스포로티오에이트, 포스포로디티오에이트, 등), 부속 모이어티 (예컨대, 폴리펩티드), 층간삽입물 (예컨대, 아크리딘, 소랄렌, 등), 킬레이터, 알킬레이터, 및 변형된 링키지 (예컨대, 알파 아노머 핵산 등)가 포함된다. 또한 수소 결합 및 다른 화학적 상호 작용을 통해 지정된 서열에 결합하는 능력에서 폴리뉴클레오티드를 모방하는 합성 분자가 포함된다. 이러한 분자는 해당 분야에 공지되어 있으며, 예를 들어, 펩티드 링키지가 분자의 골격에서 포스페이트 링키지를 대체하는 분자들을 포함한다. 다른 변형은, 예를 들어, 리보스 고리가 가교 모이어티 또는 다른 구조, 가령, "잠금" 핵산에서 발견되는 변형을 함유하는 유사체를 포함할 수 있다.
핵산 서열에 적용될 때 용어 "돌연변이된"은 핵산 서열의 뉴클레오티드가 참조 핵산 서열과 비교하여 삽입, 결실 또는 변경될 수 있음을 의미한다. 유전자좌에서 단일 변경이 이루어질 수 있거나 (점 돌연변이) 단일 유전자좌에서 다수의 뉴클레오티드가 삽입, 결실 또는 변경 될 수 있다. 또한, 핵산 서열 내의 임의의 수의 유전자좌에서 하나 이상의 변형이 이루어질 수 있다. 핵산 서열은 "에러-유발 PCR" (DNA 중합효소의 복제 충실도가 낮은 조건 하에서 PCR을 수행하기 위한 공정, 그 결과 PCR 생성물의 전체 길이를 따라 높은 비율의 점 돌연변이가 수득됨; 예를 들어, Leung et al., Technique, 1 : 11-15 (1989) 및 Caldwell and Joyce, PCR Methods Applic. 2 : 28-33 참조 (1992)); 및 "올리고뉴클레오티드-지정 돌연변이유발" (관심있는 임의의 클로닝된 DNA 단편에서 부위-특이적 돌연변이의 생성을 가능하게 하는 과정; 예를 들어, Reidhaar-Olson and Sauer, Science 241 : 53-57 (1988) 참조)와 같은 돌연변이유발 기술을 포함한 (그러나 이에 제한되는 것은 아님) 해당 분야에 공지된 임의의 방법에 의해 돌연변이 될 수 있다.
본 명세서에서 사용되는 용어 "약화하다"는 일반적으로 돌연변이, 부분 또는 완전 결실, 삽입, 또는, 유전자 서열 또는 유전자 서열의 전사를 제어하는 서열에 대하여 이루어지는 다른 변이를 비롯한 기능적 결실을 의미하며, 이는 유전자 생성물의 생성을 감소 또는 저해하거나 유전자 생성물이 기능하지 못하게 한다. 일부 예들에서 기능적 결실은 녹아웃 돌연변이로 기재된다. 약화는 또한 핵산 서열을 변경하거나, 유전자를 활성이 덜한 프로모터의 제어하에 위치시키거나, 하향 조절하거나, 관심 유전자를 표적으로 하는 간섭 RNA, 리보자임 또는 안티센스 서열을 발현시킴으로써, 또는 해당 분야에 공지된 임의의 다른 기술을 통한 아미노산 서열 변화를 포함한다. 힌 예에서, 피드백 억제 또는 생성물이 아닌 조성물 또는 반응물 (비경로 특이적 피드백)에 의해 유발되는 억제에 대한 특정 효소의 민감도는 효소 활성이 화합물의 존재에 의해 영향을 받지 않도록 감소된다. 다른 예에서, 덜 활성으로 변경된 효소는 약화된 것으로 지칭될 수 있다.
본 명세서에서 사용된 용어 "결실"은 단백질의 핵산 분자 또는 하나 이상의 아미노산으로부터 하나 이상의 뉴클레오티드의 제거를 말하며, 양측의 영역은 함께 결합된다.
본 명세서에서 사용된 용어 "녹아웃"은 발현 또는 활성 수준이 0으로 감소된 유전자를 지칭하고자 하는 것이다. 일부 예에서, 유전자는 그 코딩 서열의 일부 또는 전부의 결실을 통해 녹아웃된다. 다른 예에서, 유전자는 하나 이상의 뉴클레오티드를 오픈 리딩 프레임에 도입함으로써 녹아웃되어, 비-센스 또는 비-기능적 단백질 생성물의 번역을 가져온다.
본 명세서에서 사용되는 용어 "벡터"는 그것이 연결되어 있는 또 다른 핵산을 전달할 수 있는 핵산 분자를 지칭하고자 한다. 벡터의 한 유형은 "플라스미드"로서, 이는 일반적으로 추가 DNA 분절이 결찰될 수 있는 원형 이중 가닥 DNA 루프를 지칭하지만, 또한 선형 이중 가닥 분자, 가령, 중합효소 연쇄 반응 (PCR)에 의한 증폭으로 생성된 것도 포함한다). 다른 벡터는 코스미드, 박테리아 인공 염색체 (BAC) 및 효모 인공 염색체 (YAC)를 포함한다. 다른 유형의 벡터는 바이러스성 벡터이며, 여기서 추가적인 DNA 분절은 바이러스 게놈에 결찰 될 수 있다 (하기에서 더 상세히 논의됨). 특정 벡터는 이들이 도입되는 숙주 세포 (예를 들어, 숙주 세포에서 기능하는 복제 원점을 가지는 벡터)에서 자율 복제 가능하다. 다른 벡터는 숙주 세포로 도입 될 때 숙주 세포의 게놈에 통합 될 수 있으며, 이로써 숙주 게놈과 함께 복제된다. 또한, 특정 바람직한 벡터는 이들이 작동 가능하게 연결된 유전자의 발현을 지시 할 수 있다. 이러한 벡터를 본 명세서에서 "재조합 발현 벡터" (또는 간단히 "발현 벡터")"라고 지칭한다.
"작동적으로 연결된" 또는 "작동가능하게 연결된" 발현 조절 서열은, 발현 조절 서열이 관심 유전자와 인접해 있어 관심 유전자를 제어하는 링키지, 뿐만 아니라 트랜스로 또는 일정 거리에서 작용하여 관심 유전자를 조절하는 발현 조절 서열을 지칭한다.
용어 "발현 조절 서열"은 작동적으로 연결된 코딩 서열들의 발현에 영향을 주는데 필요한 폴리뉴클레오티드 서열을 지칭한다. 발현 조절 서열은 핵산 서열들의 전사, 전사후 사건 및 번역을 제어하는 서열이다. 발현 조절 서열은 적절한 전사 개시, 종결, 프로모터 및 인핸서 서열; 스플라이 싱 및 폴리아데닐화 신호와 같은 효율적인 RNA 처리 신호; 세포질 mRNA를 안정화시키는 서열; 번역 효율을 향상시키는 서열 (예를 들어, 리보솜 결합 부위); 단백질 안정성을 향상시키는 서열; 및 필요한 경우, 단백질 분비를 향상시키는 서열을 포함한다. 이러한 조절 서열의 성질은 숙주 유기체에 따라 다르다; 원핵 생물에서, 이러한 조절 서열은 일반적으로 프로모터, 리보솜 결합 부위 및 전사 종결 서열을 포함한다. "조절 서열"이라는 용어는, 최소한, 그 존재가 발현에 필수적인 모든 성분을 포함하며, 그 존재가 유리한 추가 성분, 예를 들어, 리더 서열 및 융합 파트너 서열을 포함 할 수 있는 것으로 한다.
용어 "조절 요소"는 핵산 분자의 전사 또는 번역에 영향을 미치는 임의의 요소를 지칭한다. 이들은 예를 들어 다음을 포함하지만 이에 제한되지는 않는다: 조절 단백질 (예를 들어, 전사 인자), 샤페론, 신호전달 단백질, RNAi 분자, 안티센스 RNA 분자, 마이크로 RNA 및 RNA 압타머. 조절 요소는 숙주 유기체에 대해 내인성 일 수 있다. 조절 요소는 또한 숙주 유기체에 대해 외인성 일 수 있다. 조절 요소는 합성적으로 생성된 조절 요소 일 수 있다.
본 명세서에서 사용된 용어 "프로모터", "프로모터 요소" 또는 "프로모터 서열"은 관심 뉴클레오티드 서열에 결찰될 때 관심 뉴클레오티드 서열의 mRNA로의 전사를 조절 할 수 있는 DNA 서열을 지칭한다. 프로모터는 반드시는 아니지만 전형적으로 mRNA로의 전사가 제어하는 관심 뉴클레오티드 서열의 5 '(즉, 상류)에 위치하고, 전사를 개시하기 위한 RNA 중합효소 및 다른 전사 인자에 의한 특이적 결합 부위를 제공한다. 프로모터는 숙주 유기체에 대해 내인성 일 수 있다. 프로모터는 또한 숙주 유기체에 대해 외인성 일 수 있다. 프로모터는 합성적으로 생성된 조절 요소 일 수 있다.
본 명세서에 기재된 재조합 유전자를 발현하는데 유용한 프로모터는 항시성 및 유도성/억제성 프로모터 둘 모두를 포함한다. 다수의 재조합 유전자가 본 발명의 조작된 유기체에서 발현되는 경우, 상이한 유전자는 상이한 프로모터에 의해 또는 별개의 오페론에서 동일한 프로모터에 의해 조절될 수 있거나, 2개 이상의 유전자의 발현은 한 오페론의 일부로서 단일 프로모터에 의해 조절될 수 있다.
본 명세서에서 사용된 용어 "재조합 숙주 세포" (또는 간단히 "숙주 세포")는 재조합 벡터가 도입된 세포를 지칭하는 것으로 한다. 이러한 용어는 특정 대상 세포 뿐만 아니라 그러한 세포의 자손을 의미하는 것으로 이해되어야 한다. 돌연변이 또는 환경적 영향으로 인해 특정 변형이 후속 세대에서 발생할 수 있기 때문에, 이러한 자손은 실제로 모 세포와 동일하지 않을 수 있지만, 본 명세서에 사용된 용어 "숙주 세포"의 범위 내에 여전히 포함된다. 재조합 숙주 세포는 배양하여 성장된 단리된 세포 또는 세포주일 수 있거나 살아있는 조직 또는 유기체에 존재하는 세포일 수 있다.
본 명세서에서 사용된 용어 "펩티드"는 짧은 폴리펩티드, 예를 들어, 전형적으로 약 50개 미만의 아미노산 길이 및 보다 전형적으로 약 30개 미만의 아미노산 길이인 것을 지칭한다. 본 명세서에서 사용된 이 용어는 구조적 그리고 이에 따른 생물학적 기능을 모방하는 유사체 및 모방체를 포함한다.
용어 "폴리펩티드"는 자연-발생 및 비-자연 발생 단백질 모두, 그리고 이의 단편, 돌연변이체, 유도체 및 유사체를 포함한다. 폴리펩티드는 모노머 또는 폴리머일 수 있다. 또한, 폴리펩티드는 각각 하나 이상의 별개의 활성을 가지는 다수의 상이한 도메인을 포함 할 수 있다.
용어 "단리된 단백질" 또는 "단리된 폴리펩티드"는, 그 기원 또는 유도 출처에 의해, (1) 본래 상태에서 이를 수반하는 자연적으로 관련된 구성성분들과 연결되어 있지 않거나, (2) 순도가 다른 세포 물질의 존재에 대해 조정될 수 있는 (예컨대, 동일한 종으로부터의 다른 단백질들이 없는), 자연에서 발견되지 않는 순도로 존재하거나, (3) 상이한 종의 세포에 의해 발현되거나, 또는 (4) 자연에서 나타나지 않는 (예컨대, 자연에서 발견되는 폴리펩티드의 단편이거나, 자연에서 발견되지 않는 아미노산 유사체 또는 유도체 또는 표준 펩티드 결합 이외의 링키지를 포함함) 단백질 또는 폴리펩티드이다. 그러므로, 화학적으로 합성된 또는 이것이 자연적으로 유래되는 세포와 상이한 세포 시스템에서 합성된 폴리펩티드는 이의 자연적으로 연관된 구성성분들로부터 "단리될" 것이다. 폴리펩티드 또는 단백질은 또한 해당 분야에 공지된 단백질 정제 기술을 사용하여 단리에 의해 자연적으로 연관된 성분이 실질적으로 없도록 만들 수 있다. 그리하여 정의되는 "단리된"은 전술한 단백질, 폴리펩티드, 펩티드 또는 올리고펩티드가 본래의 환경으로부터 물리적으로 제거될 것을 반드시 요구하지는 않는다.
용어 "폴리펩티드 단편"은 전장 폴리펩티드와 비교하여 결실, 예를 들어, 아미노-말단 및/또는 카르복시-말단 결실을 가지는 폴리펩티드를 지칭한다. 바람직한 구체예에서, 폴리펩티드 단편은 단편의 아미노산 서열이 자연 발생 서열의 상응하는 위치와 동일한 인접 서열이다. 단편은 전형적으로 5, 6, 7, 8, 9 또는 10개 이상의 아미노산 길이, 바람직하게는 12, 14, 16 또는 18개 이상의 아미노산 길이, 더욱 바람직하게는 20개 이상의 아미노산 길이, 보다 바람직하게는 25, 30, 35, 40 또는 45개 이상의 아미노산, 훨씬 더 바람직하게는 50 또는 60개 이상의 아미노산 길이, 및 더욱 더 바람직하게는 70개 이상의 아미노산 길이이다.
단백질을 인코드하는 핵산 서열이 제 2 단백질을 인코드하는 핵산 서열과 유사한 서열을 가지는 경우, 단백질은 제 2 단백질에 대해 "상동성"을 가지거나 "상동성"이다. 대안적으로, 두 단백질이 "유사한" 아미노산 서열을 가지는 경우 단백질은 제 2 단백질과 상동성을 가진다. (따라서, "상동성 단백질"이라는 용어는 두 단백질이 유사한 아미노산 서열을 가지는 것을 의미하는 것으로 정의된다.) 본 명세서에서 (특히 예측된 구조적 유사성과 관련하여) 사용되는, 아미노산 서열의 두 영역 사이의 상동성은 기능의 유사성을 암시하는 것으로 해석된다.
단백질 또는 펩티드와 관련하여 "상동성"이 사용되는 경우, 동일하지 않은 잔기 위치는 종종 보존적 아미노산 치환으로 인해 다른 것으로 인정된다. "보존적 아미노산 치환"은 아미노산 잔기가 유사한 화학적 특성 (예를 들어, 전하 또는 소수성)을 가지는 측쇄 (R 기)를 보유한 또 다른 아미노산 잔기로 치환되는 것이다. 일반적으로, 보존적 아미노산 치환은 단백질의 기능적 특성을 실질적으로 변화시키지 않을 것이다. 보존적 치환으로 인해 둘 이상의 아미노산 서열이 서로 상이한 경우, 서열 동일성 퍼센트 또는 상동성 정도는 치환의 보존적 성질을 보정하기 위해 상향 조정될 수 있다. 이러한 조정을 실시하는 수단은 숙련된 기술자에게 잘 알려져 있다. 예컨대, Pearson, 1994, Methods Mol. Biol. 24:307-31 및 25:365-89을 참고하라 (본 명세서에 참고문헌으로 포함됨).
20개의 전형적인 아미노산 및 그 약어는 전형적인 사용에 따른다. Immunology-A Synthesis (Golub and Gren eds., Sinauer Associates, Sunderland, Mass., 2nd ed. 1991)를 참고하면 되며, 이는 본 명세서에 참고문헌으로 포함된다. 20개의 종래 아미노산, 비자연 아미노산, 가령, α-, α-이치환 아미노산, N-알킬 아미노산, 및 이의 비전형적 아미노산들의 입체이성질체 (예컨대, D-아미노산) 또한 본 발명의 폴리펩티드에 적합한 성분이 될 수 있다. 비전형적인 아미노산들의 예에는 다음이 포함된다: 4-하이드록시프롤린, γ-카르복시글루타메이트, ε-N,N,N-트라이메틸리신, ε-N-아세틸리신, O-포스포세린, N-아세틸세린, N-포름일메티오닌, 3-메틸히스티딘, 5-하이드록시리신, N-메틸아르기닌, 및 다른 유사한 아미노산 및 이미노산 (예컨대, 4-하이드록시프롤린). 본 출원에서 사용되는 폴리펩티드 명명법에서, 표준 용법 및 관례에 따라 왼쪽 단부는 아미노 말단 단부에 상응하고 오른쪽 단부는 카르복시-말단 단부에 상응한다.
하기 6개 그룹은 각각 서로에 대해 보존적 치환인 아미노산을 포함한다: 1) 세린 (S), 트레오닌 (T); 2) 아스파르트 산 (D), 글루탐산 (E); 3) 아스파라긴 (N), 글루타민 (Q); 4) 아르기닌 (R), 리신 (K); 5) 이소류신 (I), 류신 (L), 메티오닌 (M), 알라닌 (A), 발린 (V) 및 6) 페닐알라닌 (F), 티로신 (Y), 트립토판 (W).
때때로 서열 동일성 퍼센트라고도 하는 폴리펩티드에 대한 서열 상동성은 전형적으로 서열 분석 소프트웨어를 사용하여 측정된다. 예컨대, Sequence Analysis Software Package of the Genetics Computer Group (GCG), University of Wisconsin Biotechnology Center, 910 University Avenue, Madison, Wis. 53705를 참고하라. 단백질 분석 소프트웨어는 보존적 아미노산 치환을 포함하여 다양한 치환, 결실 및 다른 변형에 해당하는 상동성의 척도를 사용하여 유사한 서열을 매칭시킨다. 예를 들면, GCG는 "Gap" 및 "Bestfit"와 같은 프로그램을 포함하며, 이 프로그램을 기본 매개변수와 함께 사용하여, 밀접하게 관련된 폴리펩티드들, 가령, 상이한 종의 유기체들의 상동성 폴리펩티드들 간, 또는 야생형 단백질과 이의 뮤테인 간의 서열 상동성 또는 서열 동일성을 결정할 수 있다. 예컨대, GCG Version 6.1을 참고하라.
상이한 유기체들의 수많은 서열들을 포함하는 데이터베이스와 특정 폴리펩티드 서열을 비교할 때 유용한 알고리즘은 컴퓨터 프로그램 BLAST (Altschul 외, J. Mol. Biol. 215:403-410 (1990); Gish and States, Nature Genet. 3:266-272 (1993); Madden 외, Meth. Enzymol. 266:131-141 (1996); Altschul 외, Nucleic Acids Res. 25:3389-3402 (1997); Zhang and Madden, Genome Res. 7:649-656 (1997)), 특히 blastp 또는 tblastn (Altschul 외, Nucleic Acids Res. 25:3389-3402 (1997))이다.
BLASTp에 대한 바람직한 매개변수들은 다음과 같다: 예상값: 10 (기본값); 필터: seg (기본값); 갭 오픈 코스트: 11 (기본값); 갭 확장 코스트: 1 (기본값); 최대 정렬: 100 (기본값); 워드 크기: 11 (기본값); 디스크립션 수: 100 (기본값); 행렬: BLOWSUM62.
BLASTp에 대한 바람직한 매개변수들은 다음과 같다: 예상값: 10 (기본값); 필터: seg (기본값); 갭 오픈 코스트: 11 (기본값); 갭 확장 코스트: 1 (기본값); 최대 정렬: 100 (기본값); 워드 크기: 11 (기본값); 디스크립션 수: 100 (기본값); 벌점 행렬: BLOWSUM62. 상동성을 위해 비교되는 폴리펩티드 서열들의 길이는 일반적으로 최소한 약 16개 아미노산 잔기들, 통상적으로 최소한 약 20개 잔기들, 보다 통상적으로 최소한 약 24개 잔기들, 전형적으로 최소한 약 28개 잔기들, 그리고 바람직하게는 약 35개 이상의 잔기들이 될 것이다. 다수의 상이한 유기체들의 서열을 포함하는 데이터베이스를 검색할 때, 아미노산 서열을 비교하는 것이 바람직하다. 아미노산 서열을 사용한 데이터베이스 검색은 해당 분야에 공지된 blastp 이외의 알고리즘에 의해 측정 될 수 있다. 예를 들면, 폴리펩티드 서열들은 GCG Version 6.1의 프로그램인 FASTA를 사용하여 비교될 수 있다. FASTA는 문제(query) 서열과 검색 서열간의 가장 잘 겹쳐지는 영역의 정렬 및 서열 동일성 퍼센트를 제공한다. Pearson, Methods Enzymol. 183:63-98 (1990) (본 명세서에 참고문헌으로 포함됨). 예를 들어, 아미노산 서열 간의 서열 동일성 퍼센트는 참고문헌으로 포함되는 GCG 버전 6.1에 제공된 바와 같이, 그의 디폴트 매개변수 (워드 크기 2 및 PAM250 스코어링 매트릭스)를 갖는 FASTA를 사용하여 결정될 수 있다.
본 명세서 및 청구범위 전반에 걸쳐, "포함한다(comprise)"라는 단어 또는 "포함하는(comprises)" 또는 "포함하는(comprising)"과 같은 변형은 명시된 정수 또는 정수 그룹을 포함하지만, 다른 정수 또는 정수 그룹을 배제하지 않는다는 것을 의미하는 것으로 이해될 것이다.
예시적인 방법 및 재료들을 하기에 설명하고 있으나, 본 명세서에 기재된 방법 및 재료들과 유사하거나 균등한 방법들 및 재료 또한 본 발명의 실시에 사용될 수 있으며 이는 숙련된 기술자에게 명백할 것이다. 본 출원에서 언급된 모든 간행물 및 그 밖의 다른 참고문헌들은 전부 본 출원에 참고문헌으로 포함된다. 충돌이 있는 경우, 정의를 비롯하여 본 명세서의 내용이 우선한다. 재료, 방법 및 실시예들은 단지 설명을 위한 것이며 제한을 하고자 하는 것이 아니다.
개요
본 발명은, 예를 들어, 프로테아제 분해를 감소시킴으로써 표적 세포에서 전장 길이의 원하는 생성물의 생성을 증가시키기 위한 재조합 균주 및 재조합 균주의 생성 방법을 제공한다.
일부 구체예들에서, 피키아 파스토리스에서 프로테아제 활성을 약화시키기 위하여, 이들 효소를 인코드하는 유전자를 불활성화 또는 돌연변이시켜 활성을 감소시키거나 제거한다. 이것은 유전자 조절 요소의 변형을 통한 유전자 자체의 돌연변이 또는 삽입을 통해 이루어질 수 있다. 이것은 표준 효모 유전학 기술을 통해 구현 될 수 있다. 이러한 기술의 예는 이중 상동 재조합을 통한 유전자 대체를 포함하며, 여기서 불 활성화될 유전자에 연접하는 상동 영역들은 선별 마커 유전자 (가령, 항생제 내성 유전자 또는 효모 균주의 영양요구성을 보충하는 유전자)에 연접하는 벡터에서 클로닝된다.
대안 적으로, 상동성 영역은 PCR-증폭되고 중첩 PCR을 통해 선별 마커 유전자에 연결될 수 있다. 이어서, 이러한 DNA 단편은 해당 분야에 공지된 방법, 예를 들어, 전기천공법을 통해 피키아 파스토리스내에 형질전환된다. 이어서 선택적 조건하에서 성장하는 형질전환체들을 표준 기술, 예컨대, 게놈 DNA에 대한 PCR 또는 서던 블롯에 의해 유전자 파괴 발생에 대해 분석하였다. 대안적인 실험에서, 유전자 불활성화는 단일 상동 재조합을 통해 구현될 수 있으며, 이 때, 예를 들어, 유전자 ORF의 5 ' 단부는 선별 마커 유전자를 또한 함유하는 프로모터없는 벡터 상에 클로닝된다. 표적 유전자 상동성 단편에서 벡터만을 절단하는 제한 효소에 의한 분해를 통해 이러한 벡터를 선형화할 때, 이러한 벡터는 피키아 파스토리스 내에 형질전환된다. 표적 유전자 부위에서의 통합은 게놈 DNA에서의 PCR 또는 서던 블롯을 통해 확인된다. 이러한 방식으로, 벡터 상에 클로닝된 유전자 단편의 복제가 게놈에서 구현되고, 다음과 같은 표적 유전자 좌위의 2개의 복제본이 생성된다:ORF가 불완전하여, 단축된 비활성 단백질을 발현시키는 제 1 복제본, 및 전사를 유도하는 프로모터가 없는 제 2 복제본.
대안적으로, 트랜스포존 돌연변이유발을 사용하여 표적 유전자를 불활성화시킨다. 이러한 돌연변이체의 라이브러리는 PCR을 통해 표적 유전자에서의 삽입 발생에 대해 스크리닝 될 수 있다.
조작된/녹아웃 균주의 기능적 표현형 (즉, 결핍)은 해당 분야에 공지된 기술을 사용하여 평가 될 수 있다. 예를 들어, 프로테아제 활성에서 조작된 균주의 결핍은 해당 분야에 공지된 임의의 다양한 방법, 그 중에서도, 예컨대, 발색 프로테아제 기질의 가수분해 활성 분석, 선택된 프로테아제에 대한 기질 단백질의 밴드 이동 등을 사용하여 확인할 수 있다.
본 명세서에 기재된 프로테아제 활성의 약화는 녹아웃 돌연변이 이외의 메커니즘을 통해 구현 될 수 있다. 예를 들면, 원하는 프로테아제는 핵산 서열을 변경하거나, 유전자를 활성이 덜한 프로모터의 제어하에 위치시키거나, 하향 조절하거나, 관심 유전자를 표적으로 하는 간섭 RNA, 리보자임 또는 안티센스 서열을 발현시킴으로써, 또는 해당 분야에 공지된 임의의 다른 기술을 통한 아미노산 서열 변화에 의해 약화될 수 있다. 바람직한 균주에서, PAS_chr4_0584 (YPS1-1) 및 PAS_chr3_1157 (YPS1-2) (예컨대, 서열 번호: 66 및 67을 포함하는 폴리펩티드)에서 인코드되는 프로테아제들의 프로테아제 활성은 상기 기재된 임의의 방법에 의해 약화된다. 일부 양상들에서, 본 발명은 메탄올자화 효모 균주, 특히 피키아 파스토리스 균주에 관한 것이며, 이 때 YPS1-1 및 YPS1-2 유전자 (예컨대, 서열 번호: 1 및 서열 번호: 2에 제시됨)는 불활성화 되어있다. 일부 구체예에서, 균주에 의해 발현되는 원하는 단백질 생성물의 프로테아제 활성을 추가로 감소시키기 위해 본 명세서에 제공된 방법에 따라 추가 프로테아제 암호화 유전자가 녹아웃 될 수 있다.
재조합 균주의 제조
본 발명은, 예를 들어, 재조합 유전자를 전달하는 벡터를 사용하여 활성을 감소시키기 위해 또는 필요에 따라 내인성 유전자를 녹아웃시키거나 다른 방식으로 약화시키기 위해 균주를 형질전환시키는 방법을 제공한다. 이들 벡터는 복제 원점 및 선별 마커 (일반적으로 항생제 내성이지만 다른 많은 방법이 가능함)를 포함하는 벡터 골격 또는 표적 세포의 염색체에 통합 될 수 있는 선형 단편의 형태를 취할 수 있다. 벡터는 선택된 유기체 및 삽입 방법에 상응하여야 한다.
벡터의 요소들이 선택되면, 벡터의 제작은 많은 다른 방식으로 수행 될 수 있다. 한 구체예에서, 모든 벡터를 개별적으로 만드는 DNA 합성 서비스 또는 방법이 사용될 수 있다.
각 벡터 (삽입 및 작동에 필요한 추가 요소 포함)에 대한 DNA를 확보하면, 이는 조립되어야 한다. 제한효소 클로닝, 평활-말단 결찰 및 오버랩 어셈블리를 포함하는 (그러나 이에 제한되는 것은 아님) 많은 어셈블리 방법이 존재한다 [예컨대, Gibson, D.G., 외, Enzymatic assembly of DNA molecules up to several hundred kilobases. Nature methods, 6(5), 343-345 (2009), 및 GeneArt Kit (http://tools.invitrogen.com/content/sfs/manuals/geneart_seamless_cloning_and_assembly_man.pdf) 참고]. 오버랩 어셈블리는 모든 요소가 올바른 위치에 어셈블되도록 그리고 원하지않는 서열이 도입되지 않도록 하는 방법을 제공한다.
상기 생성된 벡터는 표준 분자 생물학 기술, 예를 들어, 분자 클로닝을 사용하여 표적 세포에 삽입될 수 있다. 한 구체예에서, 표적 세포는 이들이 원하는 생성물을 제조하는데 필요한 유전자를 이미 함유하도록 이미 조작되거나 선택되지만, 이는 또한 또 다른 벡터 삽입 동안 또는 삽입 후에 수행 될 수도 있다.
유기체 및 라이브러리 요소 유형 (플라스미드 또는 게놈 삽입)에 따라, DNA를 포함하는 벡터를 세포에 통합시키기 위한 몇 가지 공지된 삽입 방법이 사용될 수 있다. 이러한 방법들은, 예를 들어, 국소 환경으로부터 DNA를 흡수하여 복제 할 수 있는 미생물의 형질전환, 전기천공법 또는 화학적 수단에 의한 형질전환, 바이러스 또는 파지에 의한 형질도입, 둘 이상의 세포의 짝짓기, 또는 상이한 세포로부터의 접합을 포함 할 수 있다.
박테리아 세포에 재조합 DNA를 도입하는 몇 가지 방법들이 해당 분야에 공지되어 있는데, 이 방법에는 형질전환, 형질도입 및 전기천공법이 포함되만 이에 제한되지는 않으며, Sambrook, 외, Molecular Cloning: A Laboratory Manual (1989), Second Edition, Cold Spring Harbor Press, Plainview, N.Y를 참고하라. 형질전환을 위한 시판 키트 및 박테리아 숙주 세포들의 비-제한적인 예들에는 NovaBlue SinglesTM (EMD Chemicals Inc., NJ, USA), Max Efficiency® DH5αTM, One Shot® BL21 (DE3) 대장균 세포, One Shot ® BL21 (DE3) pLys 대장균 세포 (Invitrogen Corp., Carlsbad, Calif., USA), XL1-Blue 적격 세포 (Stratagene, CA, USA)가 포함된다. 전기천공법을 위한 시판 키트 및 박테리아 숙주 세포들의 비-제한적인 예들에는 ZappersTM 전기적격 세포 (EMD Chemicals Inc., NJ, USA), XL1-Blue 전기천공-적격 세포 (Stratagene, CA, USA), ElectroMAXTM 아그로박테리움 투메파시엔스 (A. tumefaciens) LBA4404 세포 (Invitrogen Corp., Carlsbad, Calif., USA)가 포함된다.
진핵 세포에서 재조합 핵산을 도입시키는 몇 가지 방법이 해당 분야에 공지되어있다. 예시적인 방법은 형질 감염, 전기 천공, 리포좀 매개 핵산 전달, 숙주 세포로의 미세 주입을 포함하며, Sambrook, 외, Molecular Cloning: A Laboratory Manual (1989), Second Edition, Cold Spring Harbor Press, Plainview, N.Y.를 참고하라. 재조합 핵산을 진핵 세포에 형질감염시키기 위한 시판 키트 및 시약들의 비-제한적 예들에는 LipofectamineTM 2000, OptifectTM 시약, 칼슘 포스페이트 형질감염 키트 (Invitrogen Corp., Carlsbad, Calif., USA), GeneJammer® 형질감염 시약, LipoTAXI® 형질감염 시약 (Stratagene, CA, USA)이 포함된다. 대안적으로, 재조합 핵산은 배큘로 바이러스 벡터를 사용하여 곤충 세포 (예를 들어, sf9, sf21, High FiveTM)로 도입 될 수 있다.
각 클론을 개별적으로 테스트하기 위해 형질전환된 세포를 단리할 수 있다. 한 구체예에서, 이것은 형질전환된 세포만이 생존하고 재생하는 것을 보장하는 선별 물질을 함유하는 (또는 선별 물질이 없는) 하나 이상의 배양 배지 플레이트 상에 배양물을 스프레드하여 수행된다. 이러한 특정 물질은 항생제 (라이브러리에 항생제 내성 마커가 포함된 경우), 대사산물 누락 (영양요구균주 보완용) 또는 그 외 선별 수단일 수 있다. 세포들은 개별 콜로니들로 성장되며, 이들 각각은 단일 클론을 함유한다.
콜로니들은 원하는 단백질, 대사산물, 또는 기타 생성물의 생성에 대하여, 또는 프로테아제 활성의 감소에 대하여 스크리닝된다. 한 구체예에서, 스크리닝은 최고 (또는 충분히 높은) 생성물 생성 역가 또는 효율성을 가지는 재조합 세포들을 식별한다. 이는 세포 배양물로부터 수집된 원하는 전장 폴리펩티드의 분해 생성물 비율의 감소 또는 총량의 증가를 포함한다.
이러한 분석은 개별 클론들을, 멀티-웰 플레이트의 웰 당 하나씩 성장시킴으로써 실시될 수 있다. 세포가 적절한 바이오매스 밀도에 도달하면 메탄올로 유도된다. 일정 기간, 전형적으로 24-72 시간의 유도 후, 원심분리기에서 회전시켜 세포들을 펠렛화하고 상청액을 제거하여 배양물을 수확한다. 이어서, 각 배양물로부터 얻은 상청액은 프로테아제 활성 및/또는 단백질 분해에 대해 테스트 될 수 있다.
실크 서열
일부 구체예들에서, 본 명세서에 기재된 감소된 프로테아제 활성을 가지는 변형된 균주는 실크-유사 폴리펩티드 서열을 재조합적으로 발현시킨다. 일부 구체예들에서, 실크-유사 폴리펩티드 서열은 1) 실크 폴리펩티드 서열에서 유래한 반복 도메인들을 혼합 및 매칭시킴으로써 생성된 블록 코폴리머 폴리펩티드 조성물 및/또는 2) 산업적으로 확장가능한 미생물로부터의 분비에 의해 유용한 섬유를 형성하기에 충분히 큰 크기 (약 40kDa)를 가지는 블록 공중 합체 폴리펩티드의 재조합 발현이다. 거의 모두 공개된 거미 실크 폴리펩티드의 아미노산 서열들로부터의 서열을 비롯하여, 실크 반복 도메인 단편들로부터 조작된 큰 (대략 40 kDa 내지 대략 100 kDa) 블록 코폴리머 폴리펩티드는 본 명세서에 기재된 변형 미생물에서 발현 될 수 있다. 일부 구체예에서, 실크 폴리펩티드 서열은 섬유 형성이 가능한 고도로 발현되고 분비된 폴리펩티드를 생성하도록 매칭되고 설계된다. 일부 구체예들에서, 숙주 변형된 균주에서 프로테아제 유전자의 녹아웃 또는 프로테아제 활성의 감소는 실크 유사 폴리펩티드의 분해를 감소시킨다.
본 발명은 실크 폴리펩티드 서열 공간에 걸쳐 실크 폴리펩티드 도메인들의 조합 혼합물로부터 조작된 블록 코폴리머의 발현 및 분비를 위한 조성물을 제공하며, 여기서 블록 코폴리머는 분해가 최소이다. 일부 구체예들에서 본 발명은 분해를 최소로 하면서 확장가능한 유기체 (예를 들어, 효모, 진균 및 그람 양성 박테리아)에서 블록 코폴리머를 분비하는 방법을 제공한다. 일부 구체예들에서, 블록 코폴리머 폴리펩티드는 0 개 이상의 N-말단 도메인 (NTD), 1 개 이상의 반복 도메인 (REP) 및 0 개 이상의 C-말단 도메인 (CTD)을 포함한다. 구체예의 일부 양상들에서, 블록 코폴리머 폴리펩티드는 >100개 아미노산의 단일 폴리펩티드 사슬이다. 일부 구체예들에서, 블록 코폴리머 폴리펩티드는 국제 특허 공개공보 WO/2015/042164, “Methods and Compositions for Synthesizing Improved Silk Fibers” (그 전문이 참고문헌으로 포함됨)에 개시된 블록 코폴리머 폴리펩티드의 서열에 최소한 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 또는 99% 동일한 도메인을 포함한다.
몇 가지 유형들의 고유 거미 실크가 확인된 바 있다. 각각의 천연 방적 실크 유형의 기계적 특성은 그 실크의 분자 조성에 밀접하게 연결되어있는 것으로 여겨진다. 예컨대, Garb, J.E., 외, Untangling spider silk evolution with spidroin terminal domains, BMC Evol. Biol., 10:243 (2010); Bittencourt, D., 외, Protein families, natural history and biotechnological aspects of spider silk, Genet. Mol. Res., 11:3 (2012); Rising, A., 외, Spider silk proteins: recent advances in recombinant production, structure-function relationships and biomedical applications, Cell. Mol. Life Sci., 68:2, pg. 169-184 (2011); 및 Humenik, M., 외, Spider silk: understanding the structure-function relationship of a natural fiber, Prog. Mol. Biol. Transl. Sci., 103, pg. 131-85 (2011)을 참고하라. 예를 들면:
아시니폼 (AcSp) 실크는 적당히 높은 강도와 적당히 높은 탄력성이 결합된 결과, 높은 인성을 가지는 경향이 있다. AcSp 실크는 종종 폴리 세린 및 GPX의 모티프를 포함하는 큰 블록 ( "앙상블 반복") 크기를 특징으로 한다. 튜불리폼 (TuSp 또는 원통형) 실크는 보통의 강도 및 높은 탄력성으로 인해 큰 직경을 가지는 경향이 있다. TuSp 실크는 폴리 세린 및 폴리 트레오닌 함량 및 짧은 폴리 알라닌 경로를 특징으로 한다. 메이저 엠풀레이트 (MaSp) 실크는 높은 강도 및 보통의 탄력성을 가지는 경향이 있다. MaSp 실크는 다음 두 가지 아형들 중 하나 일 수 있다: MaSp1 및 MaSp2. MaSp1 실크는 일반적으로 MaSp2 실크보다 탄력성이 작고, 폴리 알라닌, GX, 및 GGX 모티프로 특징된다. MaSp2 실크는 폴리 알라닌, GGX, 및 GPX 모티프로 특징된다. 마이너 엠풀레이트 (MiSp) 실크는 보통의 강도 및 보통의 탄력성을 가지는 경향이 있다. MiSp 실크는 GGX, GA, 및 폴리 A 모티프로 특징되며, 종종 대략 100개 아미노산의 스페이서 요소들을 내포한다. 편모 (Flag) 실크는 매우 높은 탄력성과 보통의 강도를 가지는 경향이 있다. Flag 실크는 보통 GPG, GGX, 및 짧은 스페이서 모티프로 특징된다.
각 실크 유형의 특성은 종마다 다를 수 있으며, 독특한 라이프스타일 (예컨대, 앉아있는 거미줄 스피너 대 베가본드 사냥꾼)을 이끄는 거미 또는 진화적으로 오래된 거미는 위의 설명과 다른 특성을 가진 실크를 제조할 수 있다 (거미 다양성 및 분류의 설명에 관하여, Hormiga, G., 및 Griswold, C.E., Systematics, phylogeny, and evolution of orb-weaving spiders, Annu. Rev. Entomol. 59, pg. 487-512 (2014); 및 Blackedge, T.A. 외, Reconstructing web evolution and spider diversification in the molecular era, Proc. Natl. Acad. Sci. U.S.A., 106:13, pg. 5229-5234 (2009) 참고). 그러나, 천연 실크 단백질의 반복 도메인과 서열 유사성 및/또는 아미노산 조성 유사성을 가지는 합성 블록 코폴리머 폴리펩티드는 상응하는 천연 실크 섬유의 특성을 재현하는 상업적 규모의 일관된 실크-유사 섬유를 제조하는데 사용될 수 있다.
일부 구체예들에서, 추정 실크 서열들의 목록은 관련 용어들, 예컨대 “스피드로인”,“피브로인",“MaSp”에 관해 GenBank를 검색함으로써 컴파일 될 수 있으며, 독립적인 시퀀싱 시도를 통해 수득된 추가 서열들과 함께 풀링될 수 있다. 이어서 서열들은 아미노산으로 번역되고, 중복 엔트리에 대해 필터링되고, 수동적으로 도메인들 (NTD, REP, CTD)로 분할된다. 일부 구체예들에서, 후보 아미노산 서열들은 피키아 (코마가타엘라) 파스토리스에서의 발현을 위해 최적화된 DNA 서열로 역번역된다. DNA 서열들은 각각 발현 벡터로 클론되고 피키아 (코마가타엘라) 파스토리스로 형질전환된다. 일부 구체예들에서, 성공적인 발현 및 분비를 나타내는 다양한 실크 도메인들은 이어서 조합 방식으로 어셈블되어 섬유 형성이 가능한 실크 분자를 형성한다.
실크 폴리펩티드는 특징적으로 비-반복 영역 (예를 들어, C-말단 및 N-말단 도메인)이 연접된 반복 도메인 (REP)으로 구성된다. 한 구체예에서, C-말단 및 N-말단 도메인 모두는 75-350개 아미노산 길이이다. 반복 도메인은 도 1에 도시된 바와 같이 계층 구조를 나타낸다. 이러한 반복 도메인은 일련의 블록들 (반복 유닛으로도 지칭됨)을 포함한다. 실크 반복 도메인 전체에 걸쳐 블록들은, 때로는 완전하게 때로는 불완전하게 (준-반복 도메인을 구성함) 반복된다. 블록들의 길이 및 조성은 상이한 실크 유형에 따라 그리고 상이한 종들에 걸쳐 달라진다. 표 1은 선택된 종 및 실크 유형들로부터 얻은 블록 서열들의 예를 열거하며, 추가 예들은 Rising, A. 외, Spider silk proteins: recent advances in recombinant production, structure-function relationships and biomedical applications, Cell Mol. Life Sci., 68:2, pg 169-184 (2011); 및 Gatesy, J. 외, Extreme diversity, conservation, and convergence of spider silk fibroin sequences, Science, 291:5513, pg. 2603-2605 (2001)에 제시되어 있다. 일부 예에서, 블록들은 규칙적인 패턴으로 배열되어, 해당 실크 서열의 반복 도메인에서 여러번 (보통 2-8회) 나타나는 큰 매크로-반복을 형성할 수 있다. 반복 도메인 또는 매크로-반복 내 반복된 블록 및 반복 도메인 내 반복된 매크로-반복은 스페이싱 요소에 의해 분리 될 수 있다. 일부 구체예들에서, 블록 서열들은 폴리A 영역을 수반하는 글리신 풍부 영역을 포함한다. 일부 구체예들에서, 짧은 (~1-10개) 아미노산 모티프는 블록 내 여러번 나타난다. 본 발명의 목적을 위해, 상이한 천연 실크 폴리펩티드들로부터 얻은 블록들은 원 순열 (circular permutation)을 고려하지 않고 선택 될 수 있다 (즉, 실크 폴리펩티드들 간에 다른 방식으로 유사한 식별된 블록들은 원 순열로 인해 정렬하지 않을 수 있다). 그러므로, 예를 들어, SGAGG (서열 번호: 494)의 "블록"은, 본 발명의 목적에 있어, GSGAG (서열 번호: 495)과 그리고 GGSGA (서열 번호: 496)와 동일하며; 이들은 모두 서로 원 순열이다. 주어진 실크 서열에 대해 선택된 특정 순열은 무엇보다도 편의상 지정될 수 있다 (보통 G로 시작). NCBI 데이터베이스로부터 얻은 실크 서열들은 블록과 비-반복 영역들로 구분될 수 있다.
본 발명의 특정 구체예에 따른 블록 및/또는 매크로-반복 도메인으로부터 얻은 섬유-형성 블록 공중합체 폴리펩티드는 참고문헌으로 포함된 국제 특허 공개 공보 WO/2015/042164에 기재되어 있다. GenBank와 같은 단백질 데이터베이스 또는 신생경로 (de novo) 시퀀싱을 통해 얻은 천연 실크 서열은 도메인 (N-말단 도메인, 반복 도메인 및 C-말단 도메인) 별로 분류된다. 섬유로의 합성 및 어셈블리를 위해 선택된 N-말단 도메인 및 C-말단 도메인 서열은 천연 아미노산 서열 정보 및 본 명세서에 기재된 다른 변형을 포함한다. 반복 도메인은 중요한 아미노산 정보를 포착하는 동시에 아미노산을 인코드하는 DNA의 크기를 쉽게 합성가능한 단편들로 감소시키는 대표적인 블록, 일반적으로 실크의 유형에 따라 1 내지 8 개의 대표적인 블록을 함유하는 반복 서열로 분해된다. 일부 구체예들에서, 적절하게 형성된 블록 코폴리머 폴리펩티드는 하나 이상의 반복 서열을 포함하는 하나 이상의 반복 도메인을 포함하고, 선택적으로 N-말단 도메인 및/또는 C-말단 도메인에 연접된다.
일부 구체예들에서, 반복 도메인은 하나 이상의 반복 서열을 포함한다. 일부 구체예들에서, 반복 서열은 150-300개 아미노산 잔기들이다. 일부 구체예들에서, 반복 서열은 복수의 블록들을 포함한다. 일부 구체예들에서, 반복 서열은 복수의 매크로-반복을 포함한다. 일부 구체예들에서, 하나의 블록 또는 매크로-반복은 다수의 반복 서열들에 걸쳐 분할된다.
일부 구체예들에서, DNA 어셈블리 요건을 충족시키기 위해 반복 서열은 글리신으로 시작하고 페닐알라닌 (F), 티로신 (Y), 트립토판 (W), 시스테인 (C), 히스티딘 (H), 아스파라긴 (N), 메티오닌 (M) 또는 아스파르트산 (D)으로 끝날 수 없다. 일부 구체예들에서, 반복 서열들 중 일부는 천연 서열과 비교하여 변경될 수 있다. 일부 구체예들에서, 반복 서열은 (F, Y, W, C, H, N, M 또는 D에서 종결되는 것을 피하기 위해) 폴리펩티드의 C 말단에 세린을 추가함으로써 변경 될 수 있다. 일부 구체예들에서, 반복 서열은 다른 블록의 상동성 시퀀스를 불완전 블록에 채움으로써 변형될 수 있다. 일부 구체예들에서, 반복 서열은 블록들 또는 매크로반복들의 순서를 재배열함으로써 변형될 수 있다.
일부 구체예들에서, 비-반복 N- 및 C-말단 도메인이 합성을 위해 선택될 수 있다. 일부 구체예들에서, N-말단 도메인은 SignalP에 의해 확인된 바와 같이 리딩 신호 서열의 제거에 의한 것일 수 있다 (Peterson, T.N., 외, SignalP 4.0: discriminating signal peptides from transmembrane regions, Nat. Methods, 8:10, pg. 785-786 (2011).
일부 구체예들에서, N-말단 도메인, 반복 서열, 또는 C-말단 도메인 서열은 아겔레놉시스 아페르타 (Agelenopsis aperta), 알리아티푸스 굴로수스 (Aliatypus gulosus), 아포노펠마 세에만니 (Aphonopelma seemanni), 아프토스티추스 종. (Aptostichus sp.) AS217, 아프토스티추스 종. AS220, 아라네우스 디아데마투스 (Araneus diadematus), 아라네우스 겜모이데스 (Araneus gemmoides), 아라네우스 벤트리코수스 (Araneus ventricosus), 아르지오페 아모에나 (Argiope amoena), 아르지오페 아르젠타타 (Argiope argentata), 아르지오페 브루엔니치 (Argiope bruennichi), 아르지오페 트리파스시아타 (Argiope trifasciata), 아티포이데스 리베르시 (Atypoides riversi), 아비쿨라리아 주루엔시스 (Avicularia juruensis), 보트리오시르툼 칼리포르니쿰 (Bothriocyrtum californicum), 데이노피스 스피노사 (Deinopis Spinosa), 디구에티아 카니티에스 (Diguetia canities), 돌로메데스 테네브로수스 (Dolomedes tenebrosus), 유아그루스 치소세우스 (Euagrus chisoseus), 유프로스테놉스 아우스트랄리스 (Euprosthenops australis), 가스테라칸타 맘모사 (Gasteracantha mammosa), 히포칠루스 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), 포에실로테리아 레갈리스 (Poecilotheria regalis), 테트라그나타 카우아이엔시스 (Tetragnatha kauaiensis), 또는 울로보루스 디베르수스 (Uloborus diversus)에서 유래될 수 있다.
일부 구체예들에서, 실크 폴리펩티드 뉴클레오티드 코딩 서열은 알파 짝짓기 인자 뉴클레오티드 코딩 서열에 작동적으로 연결될 수 있다. 일부 구체예들에서, 실크 폴리펩티드 뉴클레오티드 코딩 서열은 또 다른 내인성 또는 이종성 분비 신호 코딩 서열에 작동적으로 연결될 수 있다. 일부 구체예들에서, 실크 폴리펩티드 뉴클레오티드 코딩 서열은 3X FLAG 뉴클레오티드 코딩 서열에 작동적으로 연결될 수 있다. 일부 구체예들에서, 실크 폴리펩티드 뉴클레오티드 코딩 서열은 다른 친화성 태그, 가령, 6-8 His 잔기들(서열 번호: 520)에 작동적으로 연결된다.
실크-유사 폴리펩티드
일부 구체예들에서, 본 발명에 개시된 P. 파스토리스 균주는 실크-유사 폴리펩티드를 발현하기 위해 변형되어 있다. 바람직한 구체예들의 실크-유사 폴리펩티드 제작 방법은 WO 2015/042164, 특히 114-134 단락에 제공되며, 이 문헌은 본 명세서에 참고문헌으로 포함된다. 이 문헌에는 아르지오페 브루엔니치 (Argiope bruennichi) 종과 같은 MaSp2로부터 유래한 재조합 거미 실크 단백질 단편 서열들에 기초한 합성 단백질성 코폴리머가 개시되어 있다. 각각의 반복 유닛의 분자량이 약 20 kDa 보다 큰 2 내지 20개 반복 유닛을 포함하는 실크-유사 폴리펩티드가 기재되어 있다. 코폴리머의 각 반복 유닛 내에는 약 60개 이상의 아미노산 잔기가 있고, 이들은 다수의 "준-반복 유닛"으로 구성되게 된다. 일부 구체예들에서, 이 문헌에 기재된 폴리펩티드의 반복 유닛은 MaSp2 드래그라인 실크 단백질 서열에 대해 95% 이상의 서열 동일성을 가진다.
일부 구체예들에서, 실크-유사 폴리펩티드의 각 "반복 유닛"은 2 내지 20개의 "준-반복" 유닛들 (즉, n3은 2 내지 20임)을 포함한다. 준-반복은 정확한 반복이어야 할 필요는 없다. 각 반복은 연결된 준-반복으로 구성될 수 있다. 방정식 1은 본 발명에 따른 반복 유닛의 조성을 보여주며 이는 WO 2015/042164로부터 참고로 포함된 것이다. 각 실크-유사 폴리펩티드는 방정식 1에 의해 정의된 하나 이상의 반복 유닛을 가질 수 있다.
{GGY-[GPG-X1]n1-GPS-(A)n2}n3. (서열 번호: 514) (방정식 1)
가변 구성 요소 X1 ("모티프"로 명명됨)은 방정식 2에 나타낸 다음과 같은 아미노산 서열들 중 어느 하나에 따르며 X1 은 각 준-반복 유닛 내부에서 무작위로 달라진다.
X1 = SGGQQ (서열 번호: 515) 또는 GAGQQ (서열 번호: 516) 또는 GQGPY (서열 번호: 517) 또는 AGQQ (서열 번호: 518) 또는 SQ (방정식 2).
다시 방정식 1을 보면, 방정식 1에서 "GGY-[GPG-X1]n1-GPS" (서열 번호: 521)로 나타내어지는 준-반복 유닛의 구성 요소는 "제 1 영역"으로 지칭된다. 준-반복 유닛은 부분적으로 준-반복 유닛 내부의 제 1 영역을 4 내지 8회 반복함으로써 형성된다. 즉, n1 값은 하나의 준-반복 유닛 내부에서 반복되는 제 1 영역의 수를 나타내고, n1 값은 4, 5, 6, 7 또는 8 중 어느 하나이다. "(A)n2" (서열 번호: 522)로 나타내어지는 구성 요소 (즉, 폴리A 서열)은 "제 2 영역"으로 지칭되며 각 준-반복 유닛 내부에서 아미노산 서열 "A"를 n2회 반복함으로써 형성된다 (서열 번호: 522).즉, n1 값은 하나의 준-반복 유닛 내부에서 반복되는 제 1 영역의 수를 나타내고, n1 값은 4, 5, 6, 7 또는 8 중 어느 하나이다. "(A)n2"로 나타내어지는 구성 요소 (즉, 폴리A 서열)은 "제 2 영역"으로 지칭되며 각 준-반복 유닛 내부에서 아미노산 서열 "A"를 n2회 반복함으로써 형성된다. 즉, n2 값은 하나의 준-반복 유닛 내부에서 반복되는 제 2 영역의 수를 나타내고, n2 값은 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 또는 20 중 어느 하나이다. 일부 구체예들에서, 본 발명의 폴리펩티드의 반복 유닛은 방정식 1과 2에 의해 기재되는 준-반복을 함유하는 서열에 대해 95% 이상의 서열 동일성을 가진다. 일부 구체예들에서, 본 발명의 폴리펩티드의 반복 유닛은 방정식 1과 2에 의해 기재되는 준-반복을 함유하는 서열에 대해 80% 이상, 또는 90% 이상, 또는 955 이상, 또는 99% 이상의 서열 동일성을 가진다.
추가 구체예들에서, 3개의 "긴" 준 반복에는 3개의 "짧은" 준-반복 유닛이 이어진다. 짧은 준-반복 유닛들은 n1=4 또는 5인 것들이다. 긴 준-반복 유닛들은 n1=6, 7 또는 8인 것들로 정의된다. 일부 구체예들에서, 짧은 준-반복 모두는 반복 유닛의 각각의 준-반복 유닛 내부의 동일한 위치에서 동일한 X1 모티프를 가진다. 일부 구체예들에서, 6개 중 최대 3개 준-반복 유닛은 동일한 X1 모티프를 공유한다.
추가 구체예들에서, 반복 유닛은 반복 유닛 내부의 하나의 열에서 2회 이상 나타나는 동일한 X1을 사용하지 않는 준-반복 유닛으로 구성된다. 추가 구체예들에서, 반복 유닛은 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 또는 20개 이상의 준-반복이 반복 유닛의 단일 준-반복 유닛에서 동일한 X1을 2회 이상 사용하지 않는 준-반복 유닛들로 구성된다.
그러므로, 일부 구체예들에서, 본 발명은 분해가 감소된 실크-유사 폴리펩티드를 재조합적으로 발현하여, 세포 배양물로부터 단리된 생성물에 존재하는 전장 폴리펩티드의 양을 증가시키는 효모 균주를 제공한다. 일부 구체예들에서, 실크-유사 폴리펩티드를 발현하는 균주는 PAS_chr4_0584 녹아웃 및 PAS_chr3_1157 녹아웃을 포함하는 P. 파스토리스 균주이다.
균등물 및 범위
해당 기술 분야의 숙련된 기술자들은 통상적인 실험을 통해 본 출원에 기재된 본 발명에 따른 특정 구체예들에 대한 많은 균등예들을 인식 또는 알 수 있을 것이다. 본 발명의 범위는 상기 설명에 제한되지 않으며, 그보다는 첨부한 청구범위에 제시된 바와 같다.
청구범위에서, 관사, 가령, "하나(a)", "하나 (an)" 및 "그것"은 내용상 반대 또는 달리 자명하게 나타나 있지 않은 한, 하나 또는 하나 이상을 의미할 수 있다. 그룹의 하나 또는 그 이상의 구성원들 사이에 "또는"을 포함하는 청구범위 또는 상세한 설명은, 내용상 역으로 명시되지 않거나 달리 내용으로부터 자명하지 않는 한, 그룹 구성원들 중 하나, 하나 이상, 또는 모두가 주어진 생성물 또는 과정에서 존재하거나, 사용되거나, 또는 다른 방식으로 관련되는 경우 만족되는 것으로 고려된다. 본 발명은 그룹 중 정확히 하나의 구성원이 주어진 생성물 또는 과정에서 존재하거나, 사용되거나, 또는 다른 방식으로 관련되는 구체예들을 포함한다. 본 발명은 그룹 구성원들 중 하나 이상 또는 모두가 주어진 생성물 또는 과정에서 존재하거나, 사용되거나, 또는 다른 방식으로 관련되는 구체예들을 포함한다.
또한 용어 "포함하는"은 추가 요소 또는 단계들의 포함에 개방되어 있고 이를 허용하지만 이를 필요로 하지 않음을 의미함을 유의하라. 용어 "포함하는"이 본 명세서에서 사용될 때, 용어 "~로 구성된" 또한 포함되고 개시된다.
범위가 주어지는 경우, 끝점이 포함된다. 더욱이, 달리 지시가 없는 한 또는 발명의 내용 및 해당 분야의 통상의 기술자가 이해하는 것으로부터 자명하지 않은 한, 범우로 표현된 값들은, 내용에서 명확히 달리 언급이 없는 한, 발명의 상이한 구체예들에서 언급된 범위 내 임의의 특정 값 또는 하위범위를 범위의 하한 단위의 10분의 1까지 가정할 수 있음을 이해하여야 한다.
모든 인용된 출처들, 예를 들면, 본 명세서에서 인용된 참고문헌 간행물, 데이터베이스, 데이터베이스 엔트리, 및 기술분야는 인용문헌에 명시적으로 언급되지 않은 경우에도 본 명세서에 참고문헌으로 포함된다. 인용 출처와 본 명세서의 설명이 상충하는 경우, 본 명세서의 설명이 우선하여야 한다.
섹션 및 표 제목은 제한적인 것이 아니다.
실시예
하기 내용은 본 발명을 수행하기 위한 특정 구체예의 예이다. 실시예는 오직 설명을 위하여 제공되며, 어떤 방식으로든 본 발명의 범위를 제한하고자 하는 것이 아니다. 사용되는 값들 (예컨대, 양, 온도, 등)에 관하여 정확도를 보장하기 위하여 노력을 하였으나, 일부 실험 오차 및 편차를 물론 고려하여야 한다.
달리 지시되지 않는 한, 본 발명의 실시는 숙련된 기술자에게 통상적인 단백질 화학, 생화학, 재조합 DNA 기술 및 약리학적 방법을 이용할 것이다. 이러한 기술들은 문헌에 자세히 설명되어 있다. 예컨대, T.E. Creighton, Proteins: Structures and Molecular Properties (W.H. Freeman and Company, 1993); A.L. Lehninger, Biochemistry (Worth Publishers, Inc., current addition); Sambrook, 외, Molecular Cloning: A Laboratory Manual (2nd Edition, 1989); Methods In Enzymology (S. Colowick and N. Kaplan eds., Academic Press, Inc.); Remington's Pharmaceutical Sciences, 18th Edition (Easton, Pennsylvania: Mack Publishing Company, 1990); Carey and Sundberg Advanced Organic Chemistry 3rd Ed. (Plenum Press) Vols A and B(1992)를 참고하라.
실시예 1: 18B를 발현하는 재조합 효모의 제조
먼저, 우리는 KU70 기능을 제거하여 추가 편집 및 조작을 용이하게 하기 위해 P. 파스토리스 균주를 형질전환시켰다. HIS+ 피키아 파스토리스 (코마가타엘라 파피이) 균주 GS115의 유도체 (NRRL Y15851)는 제오신 내성 마커에 연접하고 KU70 좌위를 표적하는 상동성 아암으로 구성된 DNA 카세트로 전기천공되었다. 카세트의 맵이 도 1에 도시되어 있으며, 서열들은 표 10에 제공된다. 형질전환체는 제오신으로 보충된 YPD 아가 플레이트에 도말되었다. 이는 KU70 기능을 제거시킨다.
이어서, 우리는 실크-유사 폴리펩티드를 인코드하는 재조합 유전자를 발현시키기 위해 이 균주를 변형시켰다. HIS+ 피키아 파스토리스 (코마가타엘라 파피이) 균주 GS115의 유도체 (NRRL Y15851)는 실크-유사 폴리펩티드 ("18B") (서열 번호: 463)의 발현 및 분비를 유발하기 위해 재조합 벡터 (서열 번호: 462)로 형질전환시켰다. 형질전환은 본 명세서에 참고문헌으로 포함되는 PMID 15679083에 기재된 전기천공법에 의해 구현되었다.
각 벡터는 프로모터 (pGCW14) 및 종결인자 (tAOX1 pA 신호)에 연접하는 재조합 벡터에서 실크-유사 단백질을 인코드하는 폴리뉴클레오티드 서열을 가지는 18B 발현 카세트를 포함한다. 재조합 벡터는 박테리아 및 효모 형질전환체의 선택을 위한 우세한 내성 마커 및 박테리아 복제 원점을 추가로 포함하였다. 제 1 재조합 벡터는 피키아 파스토리스 게놈 내 AOX2 좌위의 3'에 바로 18B 폴리뉴클레오티드 서열들의 통합을 지시하는 표적화 영역들을 포함하였다. 제 1 벡터에서 내성 마커는 G418에 내성을 부여하였다 (aka 제네티신).제 2 재조합 벡터는 피키아 파스토리스 게놈 내 TEF1 좌위의 3'에 바로 18B 폴리뉴클레오티드 서열들의 통합을 지시하는 표적화 영역들을 포함하였다. 제 2 벡터의 내성 마커는 하이그로마이신 B에 내성을 부여하였다.
실시예 2: 단일 프로테아제 KO 돌연변이체들의 라이브러리 생성
재조합 피키아 파스토리스 균주에서 18B의 성공적 형질전환 및 분비 후, 프로테아제들을 인코드하는 65개의 오픈 리딩 프레임 (ORFs)들은 결실에 대해 개별적으로 표적화되었다 (표 2). 세포들을 노르세오트리신 내성 마커에 연접한 ~1150 bp 상동성 아암을 가지는 DNA 카세트를 포함하는 벡터로 형질전환시켰다. 노르세오트리신 내성 마커를 포함하는 플라스미드 맵은 도 2에 도시되어 있으며, 서열들은 표 11에 제공된다.
각 표적에 사용된 상동성 아암들을 표 7에 제공된 프라이머들에 의해 증폭시켜, 노르세오트리신 내성 플라스미드에 삽입하였다. 상동성 아암들을 노르세오트리신 플라스미드에 삽입하여, 도 3A 및 도 3B에서 보는 바와 같이, 표적 프로테아제에 대해 3' 및 5' 상동성 아암이 연접한 노르세오트리신 내성 마커를 포함하는 카세트를 생성하였다. 도 3A에서, 내성 카세트 (노르 내성 카세트)는 상동성 아암 (HA1 및 HA2)에 연접되는 것으로 도시된다. 도 3B에서, 노르세오트리신 마커를 상세히 나타내는데, 이는 사카로마이세스 세레비시아에 (Saccharomyces cerevisiae)의 ILV5 유전자로부터의 프로모터 (pILV5), 스트렙토마이세스 노우르세이 (Streptomyces noursei)의 노르세오트리신 아세틸트랜스퍼라제 유전자 (nat), 및 사카로마이세스 세레비시아에 (Saccharomyces cerevisiae)의 CYC1 유전자의 폴리A 신호를 포함한다.
각 벡터의 상동성 아암들은 표 2에 제공된 65개의 원하는 프로테아제 좌위 중 하나를 표적하였다. 형질전환체들을 노르세오트리신으로 보충된 YPD 아가 플레이트에 도말하고, 30℃에서 48시간 동안 배양하였다.
실시예 3: 감소된 단백질 분해를 위한 단일 프로테아제 녹아웃 클론 테스트
생성된 클론들을 96-웰 블록들의 400 μL의 완충 글리세롤-복합 배지 (BMGY)에 접종하고 1,000 rpm에서 교반하면서 30℃에서 48시간 동안 배양하였다. 48-시간 배양 후, 4 μL의 각 배양물을 사용하여 96-웰 블록에 있는 400 μL BMGY를 접종시키고, 이어서 30℃에서 48 시간 동안 배양하였다. 재조합 단백질을 추출하기 위해 세포 배양물에 구아니딘 티오시아네이트를 2.5M 최종 농도까지 추가하였다. 5분 배양 후, 용액을 원심분리하고 상청액을 샘플링하여 웨스턴 블롯으로 분석하였다.
각 프로테아제 녹아웃의 대표적인 클론에 대한 웨스턴 블롯 데이터는 도 3에 도시된다. 단일 프로테아제 결실은 웨스턴 블롯으로 탐지된 실크 단편들의 분포에 뚜렷한 영향을 미치지 않음을 보여주었다.
실시예 4: 프로테아제 이중 녹아웃의 라이브러리 생성
개개 KO 이외에도, 상이한 짝짓기 방식의 프로테아제 조합들을 녹아웃시켰다. 이들 프로테아제들은, 부분적으로, 서로에 대해 상보적 기능을 가질 수 있는 패러로그였기 때문에 선택되었다.
이중 녹아웃을 생성하기 위하여, 실시예 2에서 제조된 단일 프로테아제 녹아웃 균주로부터 노르세오트리신 내성을 제거하고, 실시예 2에 제공된 제 2 노르세오트리신 내성 카세트로 형질전환시켜 제 2 프로테아제를 결실시켰다. 형질전환체들을 노르세오트리신으로 보충된 YPD 아가 플레이트에 도말하고, 30℃에서 48시간 동안 배양하였다. 테스트한 이중 프로테아제 녹아웃들은 표 3에 제공된다.
실시예 5: 감소된 단백질 분해를 위한 이중 프로테아제 녹아웃 클론 테스트
생성된 클론들을 96-웰 블록들의 400 μL의 완충 글리세롤-복합 배지 (BMGY)에 접종하고 1,000 rpm에서 교반하면서 30℃에서 48시간 동안 배양하였다. 48-시간 배양 후, 4 μL의 각 배양물을 사용하여 96-웰 블록에 있는 400 μL BMGY를 접종시키고, 이어서 30℃에서 48 시간 동안 배양하였다. 재조합 단백질을 추출하기 위해 세포 배양물에 구아니딘 티오시아네이트를 2.5M 최종 농도까지 추가하였다. 5분 배양 후, 용액을 원심분리하고 상청액을 샘플링하여 웨스턴 블롯으로 분석하였다.
도 4는 상이한 프로테아제 이중 녹아웃 균주로부터 얻은 대표적인 결과를 보여준다. 보는 바와 같이, 테스트한 모든 단일 녹아웃 균주에서 단백질 분해가 존재함에도 불구하고, PAS_chr4_0584 + PAS_chr3_1157 프로테아제 녹아웃 (표 3의 균주 3)의 조합은 분해 생성물들을 거의 완전히 제거하였다. 그 외 다른 프로테아제 조합들 어느 것도 분해 생성물들을 제거하지 못했다.
실시예 6: 추가 프로테아제 녹아웃 균주
실시예 4 및 5에서 본 바와 같이, 원하는 단백질 (예컨대, 18B)의 분해를 완화시키기 위해 원하는 단백질을 생성할 수 있는 변형된 피키아 파스토리스 세포를 형질전환시켜 PAS_chr4_0584 및 PAS_chr3_1157에서 프로테아제를 제거하였다. 우리는 전장 생성물의 생성을 향상시키고 분해를 최소화시키기 위하여 하나 이상의 추가 프로테아제들을 녹아웃시켰다.
각각의 추가 녹아웃을 위해, 추가 프로테아제 유전자는, 실시예 2에서 제공된 원하는 유전자를 표적하는 상동성 아암을 가진 노르세오트리신 내성 카세트로 형질전환시킴으로써 단일 프로테아제 KO (1X KO), 이중 프로테아제 KO (2X KO), 삼중 프로테아제 KO (3X KO), 또는 사중 프로테아제 KO (4X KO)로부터 결실되었다. 각 균주에서 녹아웃된 프로테아제 유전자들을 표 4에 나타낸다.
생성된 세포들을 선택 배지 플레이트 (영양요구성 또는 항생제 내성 마커)에서 단리하고, 개개 클론들을 추가 테스트를 위해 단리하였다. 개개 클론들을 다음과 같이 생성 단백질 생성 조건하에서 액체 배양 분석으로 테스트하였다: 각 균주의 분리된 콜로니들을 96-웰 블록들의 400 μL의 완충 글리세롤-복합 배지 (BMGY)에 접종하고 1,000 rpm에서 교반하면서 30℃에서 48시간 동안 배양하였다. 48시간 접종 후, 4 μL의 각 배양물을 사용하여 96-웰 블록들의 400 μL의 BMGY 또는 400 μL의 YPD (효모 추출물 펩톤 덱스트로스 배지)에 접종한 다음, 1,000 rpm에서 교반하면서 30℃에서 48시간 동안 배양하였다.
세포에 의해 발현된 단백질을 단리하고 다음과 같이 분해에 관해 분석하였다: 재조합 단백질을 추출하기 위해 세포 배양물에 구아니딘 티오시아네이트를 2.5M 최종 농도까지 추가하였다. 5분 배양 후, 용액을 원심분리하고 상청액을 샘플링하여 웨스턴 블롯으로 분석하였다.
도 5는 BMGY 또는 YPD에서 접종된 2X KO, 3X KO, 4X KO 및 5X KO 균주로부터 정제된 단백질의 웨스턴 블롯 결과를 보여준다. 보는 바와 같이, PAS_chr4_0584 + PAS_chr3_1157 프로테아제 녹아웃을 가진 균주 (표 3의 균주 3)로부터의 추가적인 프로테아제 유전자 결실은 분해 생성물을 추가적으로 제거하는 결과를 가져왔다.
다른 구체예
사용된 용어들은 제한하고자 하는 것이 아니라 설명을 위한 용어이며, 본 발명의 진정한 범위 및 사상을 벗어나지 않고 첨부된 청구 범위의 범위 내에서 변경이 이루어질 수 있음을 이해해야한다.
본 발명을 어느 정도의 길이로 그리고 어느 정도 특정하여 설명하였으나, 본 발명이 이러한 특정예 또는 구체예 또는 임의의 특정 구체예에 제한되어야 함을 의도한 것이 아니며, 선행 기술을 고려하여 이러한 청구범위에 대한 가능한 가장 넓은 해석을 제공하여, 본 발명의 의도한 범위를 효과적으로 포함하도록 첨부된 청구범위를 참고하여 해석되어야 한다.
본 명세서에 언급된 모든 간행물, 특허 출원, 특허 및 다른 참고문헌들은 그 전문이 참고문헌으로 포함된다. 충돌이 있는 경우, 정의를 비롯하여 본 명세서의 내용이 우선한다. 또한, 섹션 제목, 재료, 방법 및 실시예들은 단지 설명을 위한 것이며 제한을 하고자 하는 것이 아니다.
서열 목록
SEQUENCE LISTING
<110> BOLT THREADS, INC.
<120> MODIFIED STRAINS FOR THE PRODUCTION OF RECOMBINANT SILK
<130> 27576-37324/PCT
<140> PCT/US2017/054997
<141> 2017-10-03
<160> 522
<170> PatentIn version 3.5
<210> 1
<211> 1800
<212> DNA
<213> Pichia pastoris
<400> 1
atgttgaagg atcagttctt gttatgggtt gctttgatag cgagcgtacc ggtttccggc 60
gtgatggcag ctcctagcga gtccgggcat aacacggttg aaaaacgaga tgccaaaaac 120
gttgttggcg ttcaacagtt ggacttcagc gttctgaggg gtgattcctt cgaaagtgcc 180
tcttcagaga acgtgcctcg gcttgtgagg agagatgaca cgctagaagc tgagctaatc 240
aaccagcaat cattctactt gtcacgactg aaagttggat cacatcaagc ggatattgga 300
atcctagtgg acacaggatc ctctgattta tgggtaatgg actcggtaaa cccatactgc 360
agtagccgtt cccgcgtgaa gagagatata cacgatgaga agatcgccga atgggatccc 420
atcaatctca agaaaaatga aacttctcag aataaaaatt tttgggattg gctcgttgga 480
actagcacta gttctccttc caccgccacg gcaactggta gtggtagtgg tagtggtagt 540
ggtagtggta gtggtagtgc tgccacagcc gtatcggtaa gttctgcaca ggcaacattg 600
gattgctcta cgtatggaac gtttgatcac gctgattcct cgacgttcca tgacaataat 660
acagactttt tcatctcata cgctgatacc acttttgctt caggaatctg gggttatgac 720
gacgtcatta tcgacggcat agaggtgaaa gaactttcct tcgccgttgc agacatgacc 780
aattcctcta ttggtgtgtt aggtattgga ctgaaaggcc tagaatccac atatgctagt 840
gcatcttcgg tcagtgaaat gtatcagtat gacaatttgc cagccaagat ggtcaccgat 900
gggttgatca acaaaaatgc atactccttg tacttgaact ccaaggacgc ctcaagtggt 960
tccatcctct ttggaggtgt ggatcatgaa aaatattcgg gacaattgtt gacagttcca 1020
gtcatcaaca cactcgcttc cagtggttac agagaggcaa ttcgtttaca aattacttta 1080
aatggaatag atgtgaaaaa gggttctgac cagggaactc ttttacaagg gagatttgct 1140
gcattattgg actctggagc tacgctaacg tatgctcctt cttctgtttt aaattcaatt 1200
ggccggaacc tgggcggctc ctatgattcg tcaagacaag cttataccat tcgttgtgtt 1260
tctgcatcag ataccacttc tctggtattc aattttgggg gtgctacagt ggaagtttcc 1320
ctgtacgatc tacagattgc aacatattac accgggggaa gtgccacgca atgtcttatt 1380
ggaatattca gctctggaag tgatgagttt gtgctcggtg ataccttctt gaggtcagcc 1440
tacgtggttt acgatcttga tgggcttgaa gtgtcgcttg cccaagccaa cttcaacgaa 1500
accgattctg atgttgaggc tattacctcc agtgtacctt ccgctactcg tgcatccgga 1560
tacagttcta catggtctgg ttctgccagc ggtacagttt acacttcggt tcagatggaa 1620
tccggtgctg cttccagctc caactcttct ggatcgaata tgggttcctc ttcctcatcg 1680
tcctcttcat cgtcctcgac ttccagtgga gacgaagaag gagggagctc cgccaacagg 1740
gtccccttca gctacctttc tctctgtttg gtagttattc tcggcgtgtg tatagtatag 1800
<210> 2
<211> 1781
<212> DNA
<213> Pichia pastoris
<400> 2
atgatcatca accacttggt attgacagcc ctcagcattg cactagcaag tgcgcaactc 60
caatcgcctt tcaaggctaa caagttgcca ttcaaaaagt ttatcattcc aacgacccaa 120
aggaccgttt aattaagaga gatgactacg agtccctcga cttgagacac atcggagtct 180
tgtacactgc agagatccaa attggatctg acgaaactga aattgaggtc attgtcgaca 240
ctggttctgc cgacttgtgg gtcatcgatt ccgacgctgc cgtctgtgag ttatcctacg 300
atgagattga ggccaatagc ttttcctcgg cttctgccaa attcatggac aagatagctc 360
ctccatcaca agagctcctg gatgggctga gtgagtttgg atttgctctc gatggtgaaa 420
tttctcaata cctagccgat aaatctggac gtgtttcgaa aagagaggaa aatcaacaag 480
atttcaacat taaccgtgac gagcctgtgt gtgaacagtt tggttccttc gattctagtt 540
cttccgacac tttccaaagc aacaattcag cttttggtat tgcttacctt gatggaacca 600
ctgctaacgg aacttgggtc agggacacag tccgcatcgg cgactttgcc atcagccaac 660
agagttttgc cttagtcaac atcacagata actacatggg aatcttgggt ctcggtcctg 720
ctacccaaca aaccaccaat agtaacccaa ttgcagcaaa cagatttact tatgatggtg 780
ttgtggattc attgcggtcc caaggattta tcaattcagc atcgttttct gtttacttgt 840
ctccagatga agataacgag cacgacgaat tcagcgacgg agaaatttta tttggtgcta 900
ttgatagggc caagatagac gggccattta gacttttccc atatgtcaat ccttacaaac 960
cagtttaccc cgatcaatat acttcctacg ttacagtgtc cacaattgcg gtgtcttcgt 1020
cagatgaaac tctcattatt gaaagacgtc ctcgtttggc attaatcgat acaggtgcca 1080
ccttctccta tttgccaacc tacccattga ttcgtttagc gttttccatc catggaggct 1140
ttgaatatgt ttctcaattg ggactatttg tcattcgtac aagttctctg tctgttgcta 1200
gaaataaggt gattgagttc aagtttggtg aagacgttgt gatccaatcc ccagtttctg 1260
atcatctatt ggacgtctca ggccttttta ctgatggcca acaatactcc gcattaactg 1320
tacgtgaaag tcttgacgga ctttccattc taggtgatac attcatcaaa tcggcctact 1380
tattctttga caatgaaaac agccagctgg gtattggtca gatcaacgtc actgatgacg 1440
aggatattga ggtggtcggt gatttcacta ttgaacgaga cccagcctac tcctctactt 1500
ggtctagcga tttacctcat gaaacaccca ctagggcttt gagtactgct tcagggggag 1560
gccttggtac cggaataaac acggccacaa gtcgtgcaag ttctcgttcc acatctggct 1620
ctacttcacg aacttcttct acatctggct ctgcttctgg tacttcttca ggtgcatctt 1680
ctgctactca aaatgacgaa acatccactg atcttggagc tccagctgca tctttaagtg 1740
caacgccatg tctttttgcc atcttgctgc tcatgttgta g 1781
<210> 3
<211> 1584
<212> DNA
<213> Pichia pastoris
<400> 3
atgaacccta gcagcttaat tctacttgca ctcagcattg gctactccat tgctgagtca 60
aatttctctt tcaaacccag caagttacct ctcaaaaaac atcgtgattc ttcttccccg 120
catgaacgat ttcttaaacg agatggaccc tatcatccgc tagaagccga cgcttacttt 180
tactacacta cgtctatatt ggttggatca gaagaagaaa aagttgaagt aacagttgat 240
ttaggaacct ctgatttatg ggtcgtcgat tacaacaccg gtttatgtga tagatccttt 300
gacgaaacct atcttaaacg tagtctggat acttctgagg aagattattc tgctggagat 360
cttggctcct cagtcggtgt acgcagcgct agaaaattct tgcgcaaaag ggacaccaat 420
caaactgagg ttaatgaagc taactatggt gcttgtccaa attcgattac cttcaatcca 480
gaaaactcgt cttctttcca gagtaatgat actgctttca atatcagcta ctttgatgga 540
accagtgcta gtggtttttg ggctactgat acaatttact ttggtgacct tgaggtcagc 600
gagcaatttt ttgggctggc aaacttaaca ataagttatg gaggagtctt aggtcttggc 660
ccttccaacc tacaaacaac caatgctaac cccaacggtg aggaattcat ttacagcgga 720
gtcttagatt ccatgcgtga tcaagggctt atcaactcgg cttctttctc aatctatctc 780
aatccagaga atttcagaga tgaagataac tattctaatg aaggagcgat tttgttcgga 840
gcaattgata atgcgaagat tgacgggtca ttgaagctgt taccatacgt gacttcaggt 900
ggacactctc agattgatgc taatttcact tacatcacct tgaataatat tgccgtggct 960
gacaatgata cagccctgat cgttgagacc aacccccaat tggcaatgtt gaatccaaag 1020
tttatataca cctattttcc aaacgaagta ttgacccggc tggtaaactc tattgacaat 1080
ctagaatatg atcctgttga ggggttatat aggataagga gaacaaacat tagggatatt 1140
aacaaaaaaa tcatagagtt tcaatttggt gacgagattg tgatacattc tcccttatca 1200
aattatctgt ctgatacatg ggttccaagc acaaactaca cctatttgga gattcaggat 1260
agcagagagg atttctttat ccttggtaat gcatttttca agtctgcgta tttgtttttt 1320
gacaatgata acagtgaagt cggtattggc caactaaagg ttaccgataa ggaggacatc 1380
gttccagttg gtgaattttc tttggatcaa gattcagggt actcgtcaac ctggtcaacg 1440
ttctcctatg aaactggttc agctcccttg ggtacgtcaa ctttcgaaac gagtacaaaa 1500
actagttcag atggagctgc cccgtcggtg tctcacatta acactagttc ctacttattt 1560
gcgtttgtac tacttttcct ttag 1584
<210> 4
<211> 1422
<212> DNA
<213> Pichia pastoris
<400> 4
atgttgccca tccgcttatc caaacttctg cttttgctct ccttaaagtt gaaattgggt 60
acagctgaag aaaaatacca aaagttggat ttaaaaagaa ttgacaaaga ctattatgcc 120
gtcgatgtca aagtcggctc cgatgagcag gagatcaaag aggtactaat agatacgggt 180
tcatctgatt tctggatctt ggacaaatcg ttctgtaatt ctccaacatc agaggaagaa 240
gagaacagta acgggcgtag caacaaggaa agctgtggag tctatggctc gttcgactcc 300
aacaagtcag agacatttca ggcaactggc caagtatttg acgctgctta cggtgacacc 360
acagccgagt cgacaggatc ttcaggagtt cgaggaattg atcagctacg ggtaggagat 420
attcatatag aagaactcta ttttggacta gtgacaaaca ctacaagttt accacccgtt 480
ttaggaattg cccagctttc cgaagagttc agcaacaact cttatcctaa ctttccatac 540
cagatgaaag aggaaggtct gattgatgtt gttgcatact ctctctcctt gggccaaagt 600
aaaggtgaac tactgttcgg ggctatggac cactcaaaat ataatggaac actattgaaa 660
gcccctatat tgcaggcggg cacaccagga atgcaagttc ttttaactgg agtggccctt 720
acaaatggtt catcaagcgt cttcaatgag acagacaata aaggttttat ctactttgac 780
agtgggacta ctgcttccac tctgccatca gagcactttg atgatctttt caaccatcac 840
ggatgggcgt acgatggtga tacattgaca tattcgattc aatgcgatag tgagggagaa 900
aaatctttac ttgacttcac tttagaatat accattgctg gtaatattgt catcaaagta 960
ccatttgaag acattattat gaagaatgaa aatgatggag aatgcctctc aaccgtaatg 1020
gtgtcgaacc agacttcttt ttcatattcc gatgacacac cctttttcgt tgctggagac 1080
gaagttctgt tgaacgctta tgttgtttac aacctagaaa cacaagagct ggccattgct 1140
ccagcagtgg ataatccaga agatactgaa gaagatattg agattatctc cgcagacttt 1200
gatatttcag aagccagaga ttatagcgtt ggattagagt tcagaaatac cacaattcca 1260
gctacaactg attacttgcc ttcctcgatg tcgtcaggtt cagtcagcga agagactggt 1320
tccaagtctg agagctctac ttctgaggac tttgctgcag ccacgttgaa accatttaca 1380
ttttggggtt tcgtcctttt tttctttcac tttttgattt ga 1422
<210> 5
<211> 1839
<212> DNA
<213> Pichia pastoris
<400> 5
atgttagttg ctgttgccct agtgttgtta ctgtctacag gctatgctgg aatcgtcgcc 60
attgataccg aatatgagtt caccattggt tttcttagta cgatagaaat agggtttccc 120
ccacaaagca taacggctca atgggataca ggatcgtctg acctcttggt caattccgtg 180
acaaattcac agtgtgctca ggacggatgt agctttggtg cgttcgcctt caacaaatcc 240
accacttatt ccaatataac aaaccctaac aaccttcatg ttcagttctc ctttgcaagc 300
ggcagcgtgg ttgatgacaa acttgtgagt gacactattt ttgtagattc caaggtaatc 360
ccacggttca actttgcact ggtatcgaag ggagacctgt atggtgataa tatttttggt 420
attggaccga gagggaacca gggaacattc gattccaatg gaactccagc tttctatgat 480
agctttcctt atcacttgaa ggccctcggt ttaatcaaac gactggctta ctcattttac 540
actgggccca cccagggaaa ggtagtattt ggaggggtgg atcatggaaa gtacgatggg 600
tgcctggaga aactcgagat tgtccatgac agtgcttttt acacactgct tgaggcaatt 660
gatgctgatg atacttccgt cttggatgag caaattcatg ttttgtttga tactggtacc 720
gccttgacac tttttcccag ctttattgct gaacaactgg ctgatttttt gaaagctaca 780
tattcggacg aatacaatac gtttgtagtt ccctgcgacc aagattttga ttttgaatac 840
cttcattttg gttttcgaaa cattaagttg tcggtgcgct ttaaggatct gtttttagtc 900
attgacgata gtgtttgtgc tgtggggttt gatcaagggg cagatgcaaa caagataacc 960
tttgggtctt cacttttaag aaactactac acgctttatg atctagattc caaagaaatt 1020
ttgattgctg acgtcaagcc tgatggtcca gacgatattg aaatattatc gggtccagtt 1080
caacgaattt gtgatgaaaa gggtgtcagt agcacttcat tatggagtag tctgagtata 1140
gagtccacga tagaaccaga cacttttacc actaagcctt ctatttccca gacacggtat 1200
tcgactagct ccattggacc tcaaaacatt tctaactctt taggtgaata tccttcagtt 1260
tccgtcactc tttctgaaca ccataacact acttccatag cctcaaattc ctcattagaa 1320
gggaaaccag caactccaac tgttacagac cagtcgtacc agaataataa gactacctct 1380
accgtaattg ctgtgaattt gattacccat tcaaccactc attcaaccac tcattcaccc 1440
acctattcaa ccactcattc tagtaatgga tcacgctcaa ctttagagta cacttcaacc 1500
aaggaatcct cggtgaaaat gccctgtgcg ttgatcatct ccgacacaat tccgtacaat 1560
gcttccggtg ggaatagtag ttatggatcg ttaatttcaa catctacggt taacaatgtt 1620
gaagagaata attcaaacac tgttagacca agaaaaagac agaccttcgt ttcgggaacc 1680
acttccacga tactactcta ttcctcaact acgacccaag catatcagat gttgtcctca 1740
acttcaatcc cccgaccatc cataaaagcc agttcaaatg ctggtagccg caaaacttca 1800
aagacattat taacatttat catattgtat attttttag 1839
<210> 6
<211> 1749
<212> DNA
<213> Pichia pastoris
<400> 6
atgtaccagg cgttgttggt tttgtctctg atatgctttt cgtcggctaa ttttgttaag 60
ctgcgaagca acgctggtat gttttatgat actatggctg gagttccacg ttcagatgaa 120
gagttctggt tgcgtttgga tattaaccaa ggtctctctt ggactctgga tagtagctac 180
tactcctgta atggctcaaa tgtttcgtct tccctgtgtt tcaattctgc tcaaaacgtt 240
tacgatgctt ccaatagtcc aactgcagat ttcgttgatg tctacgcaaa cacaactgta 300
aacaatacag atgaggcatc ggccgagaga gtaaatctta caaacaactt atttgctgat 360
ggcgtttata tggaagacaa tttttacgtc acattgaata atggagcaag aatgactgct 420
acagatctga aatttttgaa tgcccacaat agtagcgccg ctgtggggtc tttggcgttg 480
gggagttaca cctcacagga cgtgccaact ttcttacaaa gactccaaag cggtggtctt 540
attgaatcca actcgttttc attggcatta aacgaaatcg attcttcata tggagagctc 600
tatttgggga caataaactc taccaagtat gtcgagcctc tggtagaatt cgattttatt 660
ccggtgtcag atcccaatgg agtttttgga ttcgattggg aagatacatt ccctacagtt 720
ccgatcagcg gattaagcat gtcttcgaat gacaaacaga gaactgtctt tttccccaat 780
gagtggaaca acacggtctt aacgggaaca tacccacttc caatgatgtt agattcaaga 840
aacatcttta tccatcttcc attctcttca atcatacata tagcagtgca gcttaatgca 900
ctgtatcttg atacacttca taaatgggcc gtgaactgtt ctgttggtca actggacgca 960
actttaaact ttcacatggg taaccttacc gttcatgctc ctatcaagga gttgatttat 1020
ccagcatacc aaggagacaa aaggctgagc tttgctaatg gagaagatgt ttgtattctt 1080
gccatggctc ctgatgttta cattggttat ccactgctag gaaccccctt tttaaggaat 1140
gcagtggttg ccgttaatca tgattcaaaa aaggtcgccg ttgccaatct taatagagat 1200
agcattcctc ccgcttcgaa cgtttctgtt tcggaatcaa tgggagttta tgttcctcca 1260
cctgtttcaa cttcaagaac atcggagaga ccgtccacac tagatgagac tagtacagcc 1320
aattttgaca aaagggaaga gtctgcaata tcatcaagtt cagtcactaa cagctcgtct 1380
agaaattctt caaccataac ttcttcagga actcaaaccg agcaaacatc aggcatagct 1440
accatcgaaa cagatagcat accaggagct ctagggaata atttaactga ttattcaacg 1500
ctgactctaa caatatacac caattccgaa gtggacgaac tcaatcctaa catagcaaca 1560
gcattcattt ccaatggttc tatttattca gagccttacc ccttttccgg aactgcagtt 1620
gctgaatcat tcagtgcatc accttcacag gctgaaggat cgaactcatc gtcctcagga 1680
tcttctttag ttttgtgttt ctttacatca ttggccagtc tgttgactgt gagctgtcta 1740
ctactgtaa 1749
<210> 7
<211> 1895
<212> DNA
<213> Pichia pastoris
<400> 7
atgtttgtga tccagctggc attcctatgt ctaggcgtca gcctaaccac tgcacaacct 60
agttcacctt tcaaggcaaa taagtttcct tttaaaaagg ttcactactc atcaaaccct 120
agcgatcgcc ttattaagcg agacaactat aagaagcttg acttgagaca tcttggcgtc 180
ttgtatactg cggaaattga aattggttca ggcaaaactg aaatcgaagt tattgttgac 240
accggatctg cagatttgtg ggtaattgac tcaaatgcag ccgtatgcga ttgtcctatc 300
ttgagataca aggtacaagt gtttccaccc ttagtcaaac tgccaacgta acacccctat 360
caggtaaact tttgaatgga cttcaagaaa ttggcattgt aactgatggc aaaatttcca 420
aaaagtttca ggaaaaccat cttttgaaga gaaacgaggc cttgaatttt gatgtcgatc 480
tgaataagcc catttgtgat caatttggat ccttcaatcc acagtcatca agaacttttc 540
aaagcaacga cacagcattt agtatcagat atctggacaa ctcttttgcc aatggatcgt 600
gggtgaggga tacggtttat gttggtgatt ttgaaattga ccagcaaagt tttgcattgg 660
ttgatatcac aaataactac atgggaattc tgggccttgg tccttctagt cagcagacaa 720
ccaatagtga tcctacagat aacagtttca cttatcttgg tattctggat tctttgcggg 780
cccaaggatt cattaattca gcctcgtact cggtttatct ggccccagat ggtaagactg 840
atgatactga tcacgatgat ggtgagatcc tgtttggtgc tatcgacgag gctaaaatta 900
atggacagtt gaagttgttt ccatatgtca atccttataa atcggtatac cctgaccaat 960
acgcttcata catcaccgtt tccagtatta ctgtagccag ttattttagt agccgcttgg 1020
ttgaaagaat ccctcaatta gctcttttag acactggtgc cacattttct tacttgccaa 1080
cttatacgct gatacgtctc gcctatgcca tccatcctgg ttttgagtat gtccgacaac 1140
tgggtttatt tattatagag tcaaacgtac tctccagtgc gagacaaagt accattgact 1200
tccggtttgg caaagacgta gtaattcgat ccaatgtttc agaccatcta ctcgacgtat 1260
cacaatactt cacatctgga cattatcttg cacttaccat ccatgaaagt gtcgatgggc 1320
ttctcatttt gggtgacacg tttatcaagt ccacctactt atttttcgac aatgataaca 1380
gtgaattggg tattggtcag atcaaaatta ccaatgacga ggatattcaa gaagttggtg 1440
aattcacctt agaacgcgat tcagactatt cttctacatg gtccatttac tcttatgaaa 1500
cttctttgga tcccttaagc actggcactg gtacggggtc aacctattct cctactcgca 1560
gtactacagc tagaagcgaa ccgactacgt ctcgacgctc caccaccctt caacccagaa 1620
caactgtgat tccttctatt gacaggcttt cattgaacag cataactagt catggttcct 1680
ctactaacgg aacctcccca actaatgaga cttcttttgc tgaggatgga ggaactttga 1740
cacccgaaga agcttctttg acaacttcac taaattctgc tactatttct gagactactt 1800
ttgtcgatgt tgaaacttct actaccaatg gtgcttcagt tgtatctttg agtgttggtc 1860
cctgcattat tgccttccta ctactcatct cttaa 1895
<210> 8
<211> 3201
<212> DNA
<213> Pichia pastoris
<400> 8
atgagcatgg gagctactgt ttcaaaggag tccactgtag acctaacact gccgctgttg 60
cagctgagtc caagactgtt gttcctgcct ggagttgtct acaagacgac tttcaagttc 120
caggaggggg tcaacatctt gctacgtttt agagacctgt tcgatgagtc tttttctgaa 180
agaaatgacg ttctaggtga tattgcccgc tcgcagaagg aacaacagga aaacgattat 240
gaccatatcc cttttttgag cagcaatgct aagaagagca taggtgtcct gaaagaccaa 300
cttgaacttg gtgggtctga tgacaagtca cttccctggg ttattgcctg tctccctggg 360
ttcgaccagt cagaccagga ctccattgcc actacaattt gtcagataac tgaggtgtcc 420
gtcgttaacc aggatattgt actatccttc gaagcattaa ccagaggatc tttaaaatcc 480
aaaaagacca tctccatgaa tgaatcaacc atatctgtgg aagtggatat accatttact 540
gaggttgacc agaccatcag taacaagctc atcttgacaa atattgataa gggtctgcaa 600
ctactggaga atatcaaaca gtttctagtc acctatcaaa atgacatgat gaaccttgaa 660
gatactacca tggaaaagaa ctcccgtcta aagtctgcaa tgatgatttt ggctccgttg 720
tctcacttga tctacgccac tgtctcatct caagaatcca ctcatgctta tactagacta 780
tccaaccagt acaagtccgc taagaaggaa ttagattcaa ccaaaaacag aaagtcttta 840
ctcaagaaga ttttgaaaac taatgatatt ctcacttcag tgttcccctt cagtatggtt 900
caaaaggtgg atgtcttggg agctatttca agttctacag acaggatcca aacaactatc 960
gacgcgttgg actttgccaa tccacttttc gaaacatatt tgaacgttga ttatgttctg 1020
gagacatgga aagattttga cactaagaac ggcaaaattg ctgccaattt gaccaggtct 1080
caattagtat ctaaccactt gaagggcctc agagtactga ttgaagacat ccaaggaact 1140
tcaagaaggc gggtcagtcc ttctcagaga actcgtttgg cgccttcgcc caatacaaat 1200
tctgcaaatc aggcaccgaa agctggagaa tcagacgacg aaaataaaga attgcgtgat 1260
tttatcaaca acctctccaa attgaagatc tcagaggatg gaaagaggct cgttaccaaa 1320
gatttcaaca gaatgactca aatgcaacca agttcatcgg agtaccaact gctcagaact 1380
tatttagaga ttattatgga tatcccatgg gaaacaaaaa atattgtaaa acaacaaatt 1440
tttgatctag acaaggccaa agaaacacta gatcaggacc attacggaat ggactccgtc 1500
aaagatagga tcttagagta tttagcagtt cttaaactcc acgatcacat taaaacgtcc 1560
aaccccaagc aagaagacga ggaaatcaaa gccagagcac ccattctctt actaacaggt 1620
ccacctggtg ttggtaaaac ttcgttagga aaatctattg caaaggctct gaacaaaaag 1680
ttccagcgag taagtcttgg aggattgaag gatgagtccg aaattaaggg acatcgcaga 1740
acttacgttg gagcaatgcc aggactattg acccaagcac tgaggaaatc tcaatctttt 1800
gatccagtga tacttttgga tgaaattgac aaggttgtcg atggatccca aggccctggt 1860
agtcgtgtaa acggtgatcc agctgctgct ttgcttgaag tgttagaccc agagcaaaat 1920
tctaacttct ctgaccatta tatcgggttc ccacttgact tgtctcgtgt tgtttttatc 1980
tgtacgtcca acgatatgag catgatcagt gccccattaa gggatagaat ggaggttatt 2040
gaactgaatg gctacaatta tttcgaaaaa gtggagattg ttaaacaatt cttattacca 2100
aagcagatca aaagaaacgg actgcctacg aatgccgaat caccatcggt ggttattcct 2160
gacgaagtga ttatgtacat cgctgtcaat tatactcggg agccaggtat tcgtaatttg 2220
gaacggttaa tagggagtat ctgtcggggt aaggctattg aatactctag cttgatgagt 2280
agtactcaag ctccaggcga aattccaaag ggatacgttt ccaaggtcac ggtagataat 2340
ctttcaaagt acattggaat acccccggaa ttgtctacag gcaagaatat gaggaatgat 2400
tcagctatct ctaaaaagta cggaatcgtg aacggcctca gttacaatag tagcggacat 2460
ggaagtaccc tagtctttga aatgaccggt atacctaata gtactaacac taacatgatt 2520
acgaccggca gattgggtga tgttcttaca gaaagtgtca agatcgcaag aacaattata 2580
agatcgatgt ttagtcacaa cttactacaa ttaaaggatg acgaaacttc aacttctggg 2640
gatcttttga agaggtttga cactactcag gttcacatgc atgtgcccgc tggtgctatt 2700
caaaaagacg gacccagtgc tggaatcacc attacgctgt gccttctgtc ggtgatgcta 2760
gagaaacctg taccaaggga tttggccatg actggagaga ttactttgag agggatggta 2820
ctgccaattg gaggtgttca tgagaagcta ctaggagcac atttaactgg aaccgttaaa 2880
agggtgatcc ttccaagaag taatcgaaga gatgtcattc aagactttat ctctaacttg 2940
gaagccaata acagaagttc tagggataag ctactggtag atcttatcaa agaggaggag 3000
tcattactgt ccaactcaaa taaatccgaa cgaattggag tgttcgggct tcctgaaaaa 3060
tgggttcaag agaagttggg acttcaagtg agctacgtgg aagaattttg ggatgttatc 3120
cagattgtct ggaacgatca ggttgaaatt gacagcacca aattacacga gctagctact 3180
aaagagttcg caaggctatg a 3201
<210> 9
<211> 1680
<212> DNA
<213> Pichia pastoris
<400> 9
atgcaattgc gtcattccgt tggattggct atcttatctg ccatagcagt ccaaggattg 60
ctaattccta acattgagtc attacccagc cagtttggtg ctaatggtga cagtgaacaa 120
ggtgtattag cccaccatgg taaacatcct aaagttgata tggctcacca tggaaagcat 180
cctaaaatcg ctaaggattc caagggacac cctaagcttt gccctgaagc tttgaagaag 240
atgaaagaag gccacccttc ggctccagtc attactaccc attccgcttc taaaaactta 300
atcccttact cttatattat agtcttcaag aagggtgtca cttcagagga tatcgacttc 360
caccgtgacc ttatctccac tcttcatgaa gagtctgtga gcaaattaag agagtcagat 420
ccaaatcact catttttcgt ttctaatgag aatggcgaaa caggttacac cggtgacttc 480
tccgttggtg acttgctcaa gggttacacc ggatacttca cggatgacac tttagagctt 540
atcagtaagc atccagcagt tgctttcatt gaaagggatt cgagagtatt tgccaccgat 600
tttgaaactc aaaacggtgc tccttggggt ttggccagag tctctcacag aaagcctctt 660
tccctaggca gcttcaacaa gtacttatat gatggagctg gtggtgaagg tgttacttcc 720
tatgttatcg atacaggtat ccacgtcact cacaaagaat tccagggtag agcatcttgg 780
ggtaagacca ttccagctgg agacgttgat gacgatggaa acggtcacgg aactcactgt 840
gctggtacca ttgcttctga aagctacggt gttgccaaga aggctaatgt tgttgccatc 900
aaggtcttga gatctaatgg ttctggttcg atgtcagatg ttctgaaggg tgttgagtat 960
gccacccaat cccacttgga tgctgttaaa aagggcaaca agaaatttaa gggctctacc 1020
gctaacatgt cactgggtgg tggtaaatct cctgctttgg accttgcagt caatgctgct 1080
gttaagaatg gtattcactt tgccgttgca gcaggtaacg aaaaccaaga tgcttgtaac 1140
acctcgccag cagctgctga gaatgccatc accgtcggtg catcaacctt atcagacgct 1200
agagcttact tttctaacta cggtaaatgt gttgacattt tcgctccagg tttaaacatt 1260
ctttctacct acactggttc ggatgacgca actgctacct tgtctggtac ttcaatggcc 1320
tctcctcaca ttgctggtct gttgacttac ttcctatcat tgcagcctgc tgctggatct 1380
ctgtactcta acggaggatc tgagggtgtc acacctgctc aattgaaaaa gaacctcctc 1440
aagtatgcat ctgtcggagt attagaggat gttccagaag acactccaaa cctcttggtt 1500
tacaatggtg gtggacaaaa cctttcttct ttctggggaa aggagacaga agacaatgtt 1560
gcttcctccg acgatactgg tgagtttcac tcttttgtga acaagcttga atcagctgtt 1620
gaaaacttgg cccaagagtt tgcacattca gtgaaggagc tggcttctga acttatttag 1680
<210> 10
<211> 1233
<212> DNA
<213> Pichia pastoris
<400> 10
atgatatttg acggtactac gatgtcaatt gccattggtt tgctctctac tctaggtatt 60
ggtgctgaag ccaaagttca ttctgctaag atacacaagc atccagtctc agaaacttta 120
aaagaggcca attttgggca gtatgtctct gctctggaac ataaatatgt ttctctgttc 180
aacgaacaaa atgctttgtc caagtcgaat tttatgtctc agcaagatgg ttttgccgtt 240
gaagcttcgc atgatgctcc acttacaaac tatcttaacg ctcagtattt tactgaggta 300
tcattaggta cccctccaca atcgttcaag gtgattcttg acacaggatc ctccaattta 360
tgggttccta gcaaagattg tggatcatta gcttgcttct tgcatgctaa gtatgaccat 420
gatgagtctt ctacttataa gaagaatggt agtagctttg aaattaggta tggatccggt 480
tccatggaag ggtatgtttc tcaggatgtg ttgcaaattg gggatttgac cattcccaaa 540
gttgattttg ctgaggccac atcggagccg gggttggcct tcgcttttgg caaatttgac 600
ggaattttgg ggcttgctta tgattcaata tcagtaaata agattgttcc tccaatttac 660
aaggctttgg aattagatct ccttgacgaa ccaaaatttg ccttctactt gggggatacg 720
gacaaagatg aatccgatgg cggtttggcc acatttggtg gtgtggacaa atctaagtat 780
gaaggaaaga tcacctggtt gcctgtcaga agaaaggctt actgggaggt ctcttttgat 840
ggtgtaggtt tgggatccga atatgctgaa ttgcaaaaaa ctggtgcagc catcgacact 900
ggaacctcat tgattgcttt gcccagtggc ctagctgaaa ttctcaatgc agaaattggt 960
gctaccaagg gttggtctgg tcaatacgct gtggactgtg acactagaga ctctttgcca 1020
gacttaactt taaccttcgc cggttacaac tttaccatta ctccatatga ctatactttg 1080
gaggtttctg ggtcatgtat tagtgctttc acccccatgg actttcctga accaataggt 1140
cctttggcaa tcattggtga ctcgttcttg agaaaatatt actcagttta tgacctaggc 1200
aaagatgcag taggtttagc caagtctatt tag 1233
<210> 11
<211> 942
<212> DNA
<213> Pichia pastoris
<400> 11
atgaagctct ccaccaattt gattctagct attgcagcag cttccgccgt tgtctcagct 60
gctccagttg ctccagccga agaggcagca aaccacttgc acaagcgtgc ttactacacc 120
gacacaacca agactcacac tttcactgag gttgttactg tctaccgaac tttgaaaccg 180
ggcgaaagta tcccaactga ctctccaagc cacggtggta aaagtactaa aaagggtaag 240
ggtagtacca ctcactctgg tgctccagga gctacctctg gtgctccaac tgacgacacc 300
acttcgacta gtggctcagt agggttacca actagcgcaa cttcagttac ctcttctacc 360
tcctctgcaa gtacaacaag cagtggaact tcagccacta gcactggtac cggtactagc 420
actagcacta gcactggtac tggtactggt actacaggca caggaaccac tagttccagc 480
actagctctt ctgctacttc gactccaacc ggttctatcg acgctatcag ccagacactt 540
ctggatactc acaatgataa gcgtgctttg cacggcgtcc cagaccttac ttggtctacc 600
gaactcgctg actacgccca aggttacgcc gattcataca cttgtggctc ttcattagaa 660
cacacaggtg gaccatacgg tgaaaatttg gcctctggat actctcctgc tggcagtgta 720
gaagcatggt acaacgagat cagcgactac gatttctcta acccaggtta ttctgctggt 780
accggtcact tcacccaagt tgtctggaaa tcaactacac agctgggctg tggatacaag 840
gagtgcagta ccgacagata ctacatcatc tgcgaatacg cacctcgtgg aaatattgtt 900
tctgccggct acttcgaaga caacgtcctg cctcctgttt ga 942
<210> 12
<211> 690
<212> DNA
<213> Pichia pastoris
<400> 12
atgactgtgc aaattttgat tgtagttacc agtgttgcta agtatgaaag cggaaagctg 60
ccaacaggct tgtggttaag tgagttgaca catatgtatc atagtgcaaa agagaacggc 120
tatgatgtga cgattgcgag tccgcaaggc ggaaacattc cgcttgaccc tgaaagcttg 180
aaatcaatgc tgattgacaa gctttcaaag gattatgaga caaaccaaga ctttatgaag 240
ttgttgcaaa acacaaaaag tttgggtgaa gtcacaggac aacagtttga cgttgtttat 300
ttggcaggtg gacacggaac aatgtatgac tttccgaaca acactgtttt acaaaacatc 360
atcaaagaac actatgaggc gggcaaaatt gttgccgctg tatgtcacgg agtttgtggg 420
cttttgaacg taaaactgtc tgatggcgag tatctaatca aagacaaggc cattacagga 480
tttaattggt ttgaagaagc tatagcagga cgcagaaaag aagtaccgtt caaccttgaa 540
gcagaattga ataaaaaaac ttcaaaatac gagaaagctt ttatcccaat gacgtcaaaa 600
gtggtcgtgg acgggaactt aatcacagga cagaacccat tcagttcaaa agaaattgcg 660
aaagtggtaa tggaacaact gaagcaataa 690
<210> 13
<211> 2517
<212> DNA
<213> Pichia pastoris
<400> 13
atgattgatg agaagcaatt gaatcaaccc aaaaggagcg tcttaagacg tctccatatg 60
ctgtttctgc cattactagc tatctccttt ttcctgatat atttaagtga tatcacacag 120
cctctcttcc gtgcccgaaa ggaagacgaa aacccgttgg aaatttactt gaaggcattg 180
gaaacgaatg aagctcacaa atggtcaaag gtgtacactt cgcagcctca tttggccgga 240
accaactacg gattggttga gtttactaag tccaaatttg aagaatatgg atttgaggcc 300
agtgtcgatg actacgatgt gtacctgagt taccctattg atcatagttt ggaattgtat 360
gagcattctg aggataaaaa tgacaagctc ttgtataagg cttcgctgca agaggacgtt 420
ctctctgaag acccaactac ttcaggcgac gacctgatcc ctaccttcct tggttacggt 480
gctaacggca atgtatctgc agaatacatc tacgctaact atggaaccaa agaggacttt 540
gaggatttgg tggcccgtgg tgttccaatc aaggggaaga tcgcagtcat tagatatggt 600
caaatattta gaggcttaaa ggtgaaattt gcccaagaat atggcgcaat cggtgctgtc 660
atatacagtg acccaggcga cgattatggt atcacccctg aaaatggtta caagccttac 720
cctcatggta aagccagaaa cccaagctct gtgcaaagag gttctgccca atttttgtct 780
gtttatcccg gtgacccaac cacgccagga gttggatcga agaagggagt agaaagagtt 840
gatcctcatg ctacaacccc ttccattcca gtcttgcctt tgagtttcaa agatgccttg 900
ccaattttga agaaacttaa taaggaagga ttgtctgttc ctgactcctg gaagggaggt 960
ctcgagggag ttgattacag taccggccca gctaaaaaca ttcatttgaa cctttatagc 1020
gaacaaaact ttactattac acctatttac aatgtctatg gagagatcaa aggtgagaat 1080
gctgacgaag ttatcattat tggtaaccat cgtgacgctt ggattaaggg aggtgcttct 1140
gaccctaaca gtggatctgc tgctttgatt gaacttagta gaggtttgca cgccctaacc 1200
aaaacaggat ggaagccaca ccgtactatt gtactagctt cctgggatgc tgaggaatat 1260
ggcttgattg gatctactga gtttggagaa cagtttgaga agttccttca gaagaaggtc 1320
gttgcctatt tgaacgttga cgttgctgta gctggaactc atcttcattt gggtgcctcg 1380
ccatctttgt tcaaactatt gaaggataat gccaaagaaa tcactttcaa gaattcaacc 1440
gagactttgt atgacaacta tgttaaagat catggcaacg acattatttc gaccttagga 1500
agtggaagtg actacactgt ctttttggat catttgggaa ttccttcgct tgatattggt 1560
ttcattgctg gaaaaggtga cccagtatat cactatcatt caaactatga ttcgtaccac 1620
tggatcagta ctagtggtga tcctggattt gagtatcata atgtactggc caaatatttg 1680
ggttcgttgg ttttgaatct ctctgagaga gaggtgttgt acctgaagct tcatgattat 1740
gctaccgaat tgctcaagta cctcttggaa gcctacgccc aaatgccaga ggaatgggac 1800
gatgaagtaa ttggtttcag atcttcctcg tgtcatcgtg cgaaagcatc tcatcatggt 1860
aaggatcctc atcatgaggg aagacgccat cacggaaaag gattccattc taaaggaggg 1920
cctcatcatg gggaacgcca tcacggaaaa ggattccacg ctgaaggggg accccaccat 1980
gagaaaggac cgcatcacga aaaagggctc cacgtcgaag gagagcccca tcatcagaaa 2040
ggacctcact ttgaaaaagg attccatcat gacatggaga tgtaccataa gaaattggct 2100
catcacggta aagaacccaa gacgaagcta aagcacttga agaaacaagt tgagagttta 2160
atcatcgatt tcgccaatac cactcaaaca tatgacgctt acactgactt ccttcagaag 2220
caacatgaga ttagggattc tctttcattc tgggagaaaa tcaagctaca ttttaagatc 2280
aaggcagcta acttcaaact taaatatttt gagcgagttt tccttcatga aaatggctta 2340
aagaacagag aatggttcaa acatattgta tatgctgcag gaaggaacac tggttacgcc 2400
ggacaaagac tgcctggtct tgtggaagcc attgaagaca agaatctgca tgatgcagta 2460
aaatggcttc acatcctttc caagaagatt gatagtctac agaagtcatt agagtag 2517
<210> 14
<211> 888
<212> DNA
<213> Pichia pastoris
<400> 14
atgagattac ttcacatttc attgctatca attatctcag tattgaccaa ggccaacgct 60
gaatgttgtt acaccaacac acatactacc actgaagtct ggtatactac agtatatgct 120
cgagatgtta gtgaagagac ttcttccaca ctggctggtg gaagtgcaac tgtcagctca 180
gaagtgagtt cgacaattga atctagcgtt gccacttccg ctaccaccga atcttcaagt 240
gagacatcag ggtccacatc tgggtccaca tctgccactg aatcatcaac tggtagtagc 300
tcgctagcaa ccagttcatc gataaccagt tcagagtctt ccaccattac acaaaccaca 360
ggacaagagt caacaagccc aaccccatcg tcctcagaga caggttcttc tactactact 420
ccctacgata taagtccaac ggcaagttcc gactttgatg cttttaaata tcaaattctt 480
gatgaacaca acataaaaag agctctacat ggagttgacg gattagagtg ggatgaagaa 540
gtatatgctg ccgcccaagc atatgctgac gcatacactt gtgacggaac cttggttcac 600
tctggaaata gtctgtacgg agaaaactta gcgtatggtt actcaaccag agggactgtt 660
gatgcctggt acagtgaaat tgaatattat gactttaata acccaggtta taccccaggt 720
gttggacatt tcactcaagt agtttggaaa agcaccacaa agctcggctg cgctttcaag 780
tactgcaatg actattacgg agcctacgtg gtatgcaact actcaccacc aggaaattat 840
gtcaacgagg gatacttcga agccaatgtg ttaccactgg tagattaa 888
<210> 15
<211> 681
<212> DNA
<213> Pichia pastoris
<400> 15
atgagttatc ccctaggtct gggtcgtaca gcttataggt tcatcccgag gtcaatctgt 60
tcaagacgat ccatctcatc ccatgcatta cctccaacgc cctccaactc accaccagca 120
ggagatttat tcaccaaact gctgaacgaa cgcatcatat atttagcagg aggcattgat 180
gatgcgcaag caacatctat cacggctcaa ttgctgtatc tggaatcgca gtcaacgtcg 240
aaacaaatca acatttacat caactcacca ggaggttctg tcacggcagg gctggccatc 300
tacgacacaa tccagtatat ccgagcgcca gtttccacgg tttgcttagg acaggcatgc 360
tccatggcat ccctcttgct tgcaagcgga acgcatggca aacgtttgat cttgccaaac 420
gctaccataa tggtgcatca accatcttcg gcaaacggaa ttaagggaca ggccactgat 480
atcgagatat atgcccgtca tatcatcaat accaaacaga aattgcaaac tttataccta 540
aaacacatgt ctccaaccat gacggtggat gaaatcactg cacttttgga gagagatcgg 600
ttcatggagc cagaggaggc agtgtctctt ggactggcgg accgtgtatt agagaggaaa 660
cccccggttg tatctgacta a 681
<210> 16
<211> 1659
<212> DNA
<213> Pichia pastoris
<400> 16
atgacagata ccaaggagtt agccacgttg ctggagaact tgttgaaatt gcaaaaatca 60
ggaagtcttg gtgaaattgt gggtcaagca cagcgcattt atcatgacat ttctgacctc 120
tcagtcctat ctggattatc aaccccagaa gtgctctctc ctcacacatc tccagatgtc 180
cccgagagag ttccatctga agtcaactta gacaattcca atctggcaac tgatgtcaac 240
gaaaaggaga agtattttga cgattttgca aatgactaca tcgagtttac ctacaagaac 300
cccaccacct accatttggt gcaatctgtg gcggaattgt tgaagaaaag cggattcgaa 360
tatcttcctg aagcagctga ctggtccaaa ttattcgacc ctgaaaagac gggagcgtat 420
ttcacaatcc ggaatggaac ctctttagct gccttcacaa ttggtagttt ctggtcccca 480
gccaagggag taggagctat cggaagtcac atcgatgctc tcacaactaa gctgaagcca 540
gtctccaata agagtaaggt tgatggctac gagttgttgg gagtttcccc ctatgctggt 600
gctttgtctg acgtctggtg ggatagagat ttgggtattg gtggaagagt aatttacaaa 660
aatgaatctt ccggcaagct ttccaccact ttggttaaca gtacacctca tcctgttgct 720
catattccaa ctttggcccc tcattttggt actccctcca acggtccatt caacaaggaa 780
acccaagcag ttcccgttgt aggattttct gacggaaacg acgaggagaa acccactgag 840
gatgaacaaa agtctccttt gattggtaag cattctttaa aactactccg ctacatatct 900
aagctagcag gagtgccagt gtcctccttg attgatttcg atttggacat attcgatgtc 960
caaaaaggta ctaggggcgg tctttccaat gagttcattt acgccccaag agtggatgat 1020
cgtatttgtt cttactctgc tctacaagcg cttatcagac gtcacaagga tcccgaatcc 1080
tttgtcacag acgactcttt caatcttgtt gccctttatg acaacgagga gatcggatct 1140
ctctccagac agggagccaa gggtggtcta cttgagtcga ccatttccag agcaatcgct 1200
gcattgaaaa tttcagagcc agggactctg caaagactat atgcaaattc agtgattctt 1260
tctgcagatg tcacacattt gttaaatccc aatttcaccg aagtgtactt ggagcaccac 1320
aagccactgc caaacacagg gattgcactt gcgctggatt cgaatggcca tatggccaca 1380
gatttgttag gcaaggtcgt tgttgagcag ctggctaaac tcaatgatga taaagtgcag 1440
tacttccaga ttcggaacga ttcaaggtct ggagggacca ttggacccag tatttccagt 1500
agtactggcg ctagaaccat tgatcttgga attccccaat tgtccatgca cagtattcgt 1560
gctaccgtgg gatacaaaga tgttggcctc gctgtcaagt ttttccaagg gttctttaaa 1620
aattggagaa aagttgtcga cggcattgaa gagttttaa 1659
<210> 17
<211> 3552
<212> DNA
<213> Pichia pastoris
<400> 17
atgacttcgg tatttttggg tgtttataga gccctatttg attaccaagc tcaaaatgac 60
gaagaactaa ctgtgcatga gaatgatcta ctatacgtat tggaaaagtc cgaaattgat 120
gactggtgga aagttaaaca acgagttatc ggagttaatg tcgaggaacc aataggtctg 180
gtacccagta cttatattga gcctgctaca cctatcgggt cagctgttgc actgtatgat 240
tatgacagac aaacagaaga agaaattact ttcaaggaga atgacacctt tgacgtgtac 300
gacaccgacg atcaggagtg gatcttggtt ggcctgaaca atatccattt tggtttcgtg 360
cctgcaaact acatacaaat ttctttgggt acgacggcac ctgcttctaa caatccacca 420
atacttagtc ccgccagctt ccctccacct cctcaacgga tcaacaactc ctctgttccc 480
tctctcaaag atgctgaacc agcaagaaat ctagaggacg ataatgctta tgaagaggag 540
gaagatgtac ctccaccaat gccaacgcga ccaactgcca ctacagctac atctaatatc 600
tctgctcctc aggactctga atccgaagag gaaccttcta gtagtagcag aaggccaagt 660
ggccgttcaa gggcggatga tgattttgta aaaggagact atttcacttg ggatgttcag 720
gaaattaatg gccgcaaaaa gaggaaagct gtcctgggta tcggaaatgg tagtatttat 780
gtccaagcag agggacattc ttctaagaaa tgggatatca ggaatttgac aaatttcagt 840
aacgaaaaaa agcacgtctt ttttgacttt accaacccct cggcatccta tgaacttcat 900
gcaggctcca aggacgcagc agatgccatc ctgtcaattg ttggtgattt gaaaggtgct 960
tcttcaatgc gtgctttgaa agaggtgaag gctgcatctt ctgccccaaa aaccaagact 1020
ggtaaagtca gttacaactt cgatgctgaa agtcccgatg agttgtcgat tagggagggt 1080
gatgttgtct acatattgaa cgataaagaa tcctctgagt ggtggatagt tcaggacgtt 1140
aatactaaca agaaaggtgt tgttccagct agctacatag agttgattag cgggggtgga 1200
tctactttag ccagcattgg ctcttctatt tccaaaggtt ctaagaaagc ttttggatcc 1260
tccagaaaac gtaaggaaaa agagcgtaag catttggaag agcaacgtgc cgctaaaaga 1320
gaaaccgaaa gggaacgtca aagacttcga tccaaggaag aaagggatag gctaagaaag 1380
ttagatgaaa aggaaagaag gaaaaagcaa aaagctactc cacaggatga agaccaaccc 1440
gagactagca aacctaatcc tcatagagtg cgtacctgga ttgacagttc aggatccttc 1500
aaagttgaag cagagtattt gggagttgtt gacggtaaga ttcatctgca taaaacaaac 1560
ggtgtaaaga ttgccgtagc ggctcctaag ttgtcactag aggatttaga gtatgtggaa 1620
agaatcactg gaatgtcgtt agaaaaatac aagccaaagc caaaatctag tggttcctat 1680
tccagacctt ccaaaaagcc atcctctaga gaatcttcac caaaggagtc cagccgctcc 1740
ggagttaaac aatcagttcc caagattgat cctcccaaag acccagatta tgattggttt 1800
caatttttct tgggttgcga tattgatccg aataattgtc agcgatacag tgtggttttc 1860
attaatgaac aactggatga gagtagtttg caagacctca ctccatccct actaagatcg 1920
ctagggttaa gagaaggtga tattttgaga gttcaaaaat tcttggataa caagtttggt 1980
cgaaccaaag ctcaagaatc tgctaccaat ggtggtttat ttaccaagag tgatggtaca 2040
ttgaagaaca ataggtccac tgatgttcta acaagtacag ttgtaacgcg agaaacttta 2100
agtcctacta aggccgaggc taagagcaaa agaattgatg acgaagcatg ggctctcaaa 2160
cccgctgccg aatctagctc tcaaatggat caattctcca gacctgtcag tgcaatgagc 2220
aaacaattga ctggatccat acaagatctc gtcaacttga aacctttggg ggacaatgca 2280
aacaacgctt cggtagccca caaagctgaa acaccaaaca ctacccagga caaaccttct 2340
gctcctgtct tggaacctgt gaagactgga gctgcaaggg gacctgtgca agcgcaacca 2400
acaagtggtg gtttcgtcac tgcacaacct actggtgctc tagttgcaat gcctacaggt 2460
ttcatgccca ttacgatggt gcccgtaaag acaggaggaa ctatagctct tcaacccact 2520
ggtggattcg tttcgttgca aagaactggt ggggtacttc cgcaggttac agggggactt 2580
gttcccgttc agactggtgg gttagtaatg cctcagacct catttggtgt aactccaact 2640
ttgcagccaa caggagggat tctacctgct cagaggacag gtggattggt tcctgttcaa 2700
aggacggggg ggctaattcc cgtccaacaa actggaagat tagttcctgt tcaacaaact 2760
ggaggattga ttcctgttca aaggactgga ggattagttc ccgttcagag aactggaaac 2820
ttacaacctg tacctacaac ctcttttgga agtcaaccaa caggaacttt tgtgcctcaa 2880
tcttcctttg gtaatcagtt ggccaccaat ttgaataacc cgcaaaccac attcggctct 2940
caaccaacag gaggtttccc tcagacatca tttgcacaaa atcagtttag acaatcgaca 3000
ggaggtttcc agcagacccc aattgtgcaa caaacagggg gattccccca atactccgct 3060
ggacaacaga cggtaggatt ccctcagaac tcttttggac agcagacagg aggaattgcc 3120
caaaactcat ttggacaaca gacaggaggt tatcaaacag gttttcaagg aaatggatcg 3180
attccaatgc cccagtcctc attcggtgct tcaaatctgg gattcaatgg tgctacgcag 3240
cagaactaca acattggcat gggccaatct ttgccagcag cttctatccc tccccttcaa 3300
ccctcttaca cctcatcact caatggaatg tcaaacatgc ttcagaacgt aagcatctct 3360
cagcagccac aacaagccca gccaatgacg acttttggag cacctgtggc ccagcctccg 3420
ttacaggctc aaccaactgg ctttggtttt ggtaactcgc cctatggagg tcagaaccca 3480
ctccaatctc agccaacagg taaaagagcc aacttatcag cagctaccgc agacaaccca 3540
ttcggcttct ag 3552
<210> 18
<211> 1662
<212> DNA
<213> Pichia pastoris
<400> 18
atgaccaacc aatcaacagt ggtggattta cgcctttcat ccaagagagt tgttggcaaa 60
ccagtcaagt tgcccacagt cctagcgtgc tcagggtcag attcttccgg tggtgcaggg 120
atcgaagcag atatcaaatc catcacggct tttgggtgct atgcgctaac agcaattaca 180
tctttaactg cccagaatac caaaggtgtc accagtatag aaaacaccga cccaaagttt 240
ttcgaagaga ttttagaggc aaattttgag gacattgaaa tcgatgtggt gaaaactgga 300
ctgttaaacc ctgagtcatc tcgtttattg ctgaaatttt tagataaata ccacaaagga 360
aagccatttg tcctggatcc ggtcttagtg gctacgtctg gttcaatgct tgcagatcaa 420
cacgaattag ggttcaccat tgattctcat tttaagaaag ctactatcat tactccaaat 480
ttcgaagagg catgtgtgat ctactcttac ttgaaaaagc tgaagactgt agatgagttg 540
ggtgaaatag aaactttaga ggatttgaaa ggaatggcca agttcatcca gcaaactaca 600
cattgcaact ctgttcttct taaaggtggc catattccct ggaatagaaa cgagcagttg 660
gttaaaaaaa agggaggaga tccagcatac attactgata ttctttatca gggtcatttg 720
gataaattca cggtaatcaa gacagattac ttgacaagtt ctggaactca tggttctggg 780
tgtacgattg ctgcctcaat tgctgcaaac attgcccgtt cgttgaagat tgaggatgct 840
gtaatttctt cgattagata cgttcatcag gcaatttttg gagcagatga gacgctagga 900
caaggaaaag gccctttgaa tcatgtgttt catatttctc ctcccattaa cggcacaagt 960
gctgagaata actttcttcc gttctatcca ggtcacttct tagattactt actggagcat 1020
cctttggtga gtcccatctg gaagaactac atcaaccacc catttttaga aaacgtagca 1080
acaaataagc tggctaagaa cagattcatc cactacattt gtcaagatta cgtgtatcta 1140
gcttcttatg cccgtgtcca cggcttagct gccggagttg cacctgatat tgaaagcata 1200
aaggcagaag cccatataat cgactccatc atggaagaaa tgcatagaca taaagacgta 1260
ttgaactctc gtggaattgt gaaactggat gaattaagac cctccaaggc ctgcaaacag 1320
tattccgact acctcctaaa cattgcgaag acatcagact gggtggccat aaaaatcgcc 1380
ttagcaccat gcatctttgg ctactattac gctgccattt atgctcggtc gtttatcaag 1440
gatgaagctg acgtggacga agaattcttg aattggatca atacgtatac cggtgattgg 1500
tacaaagatg ctgttgacga ggccagacag tcgctagaaa gccatatgca agctgtttct 1560
cccgtccagt tagcagagct agtcaagatc tttgcagatg tctgtcaatt ggaggtgaac 1620
ttctggactt cgccaatgga actaccagaa caagatctat ga 1662
<210> 19
<211> 1008
<212> DNA
<213> Pichia pastoris
<400> 19
atgcctacag tggtgactaa cgagtcctct ctcttgcaaa caaccgtgag tgttgcacca 60
ttggtgcttt tatctgttgt tgatcactac gaacgagtgg tgcaggcacc caacgcccca 120
actaattcaa acgacaaaag agtcgtgggg gtcattttgg gagacaatac aaacaagaac 180
ttgatcaagg taaccaactc atttgccatc ccgtttgaag aagacgaaaa gaacagggat 240
atttggtttt tggatcacga cttcatcgaa tcgatgatgg aaatgttcaa gaagattaat 300
gccaaagaaa gacttattgg atggtaccac tctggaccaa agttaaagtc atctgatcta 360
caaatcaacg agttattcaa gagattcact ccaaatcctt tgcttttgat tgtggatgta 420
aattccaccg atatagtcga tattcctaca gactcatatt tggcaattga agaaattaga 480
gacgatggct caagtgcaga aaaaacgttt atccatttac catccatcat ccaggccgaa 540
gaagcagaag aaattggagt ggagcatctt ctgagggata tccgagacca ggcgtgcgga 600
aatctgtcca taagattgac taacaatttc aaatcgctga agtctttaaa cgatcgcata 660
gccaacattg tccaatattt gcgcaagatt ttaagtggag aattaccaat aaataatgta 720
attcttggaa aattacagga catattcaac ttattgccca acttggttgc cgttcaaggt 780
gatcccacaa aaccagccac tgcaagtgct aaccaactag ccacatcatt caatgtgaag 840
accaatgatg aattaatgat ggtttacatc tccagtttag taagatccat cttggctttc 900
catgatttga tcgacaataa gatcgagaac aagaagaaca acgagaaaga taaggaattc 960
acaccaacag aggaagaacc ccaacaagcg gctatagaat cgaaataa 1008
<210> 20
<211> 969
<212> DNA
<213> Pichia pastoris
<400> 20
atgacaatgt caaccgaaga tatcatcgcc aggcatagga aggagaaaag ggaccaaatt 60
gcacttatta caaggatgaa gaagcagagc actaagtcaa ccaaaaagga aatcatgaaa 120
caatgctctc tcttggaaga agagctacag gcaagacata agaaggagtt aggtgagtgc 180
aagactgaaa attccgtcga gagaagtagt gagcctactg acgaaaaatc aaatggtgga 240
gaactttttt cccctgaaaa gttattatca atgatgactt taaaacagca aggaactcca 300
agtgagaatc aaggaaacgc aactgttcca aagagaaaac gcaataggca gaaggacaga 360
ttagctagaa gggaagttgc cattaaagag atgcaagcag cagcagcaaa agaggctaac 420
ctccaaacaa atttcaaaga gatagaattg aacaacataa gccaactgtg ccaagttgct 480
cacctggaac catatgatat ccgacctgat gggcattgct tgtttgcatc tataaaagat 540
cagttggagg ttcggcacaa aattgaaaat ataagtatac aagatcttcg gtctctggct 600
gcgagtcata ttaaaaatga tcccgagact tatactcctt tcctttttga tgagaatact 660
atgaaaatca gggacattga tgactatgca aacgagctgg aaaccacggc tttatgggga 720
ggtgatatgg aaattttggc attgagcaaa gagtttgatt gtccaatcag tgtaatgatt 780
agtggaagac ctattcatct tgtcaatgcc gacggttcta aagaggagtt gaagttggtt 840
tattaccgtc atgcatatgg cctaggtgag cattacaact ctttaagaga tagatcagag 900
ataagggagt cttgtatagt tgagcaagag gaaaaagaag cggtagacga tggaaaatca 960
tcttcttga 969
<210> 21
<211> 939
<212> DNA
<213> Pichia pastoris
<400> 21
atgagactta agatcaagcg ttcaaatgaa cagcggctaa taacattgcc tgacggggct 60
acagtatcgg atttacttaa tgaaattgga tcagcttcta tcaatataaa ggttgggttt 120
cctcctcaga caattgatat ctcagatacc agcaagttgc ttactgatag tggaatcaag 180
aatggtgaaa tgatcattgt cactgatacc attgaaacag aagtgcctgt caacaagaat 240
gaggttgcaa ttgccactgt ctcaaaccag aatgatgcgc cctacgttca aatagacgac 300
atcttcctag tcttgcggaa gattcccgat gataattctt gtttcttcaa ctctgtcggc 360
tactgtatat ttggtcctga ttcaatcaag tatccggatt ctcaacaaga actaagacag 420
gccgtcgcta atgtaatcag agagaacaac caaggtattt ataactccgc catcttgggt 480
ggaaagtcaa tcacagagta ttctcagtgg atccaaagca gtaattcctg gggaggagcc 540
atcgaagcac agatattggc agaatacctt gatatcagta tctggacagt ggatattgag 600
tctcttcaag tctacaaatt taatgatgaa atggcttcaa ggttttgcgt tattatgtat 660
agtggtattc attacgacgc tatggctctc aagctggaca catcattaga tgaggaggac 720
tcacaaattt gtgtgtttga taagttcagt gagttgggga ctttgattga agacaacgtt 780
ctcaaattaa ccaaccatct taagaaccag ggctattata cgaatacttc cacattcata 840
ctccaatgtc aaatatgtct cgcaacattg caaggagaaa aagaagcaaa tagccacgca 900
aagaaaactg gccacacaaa ttttggtgaa gtcaattga 939
<210> 22
<211> 5528
<212> DNA
<213> Pichia pastoris
<400> 22
atgtcattgt ctgatcctga ggacagccta agacgtctac ttgtgagttt accctccaat 60
gttaagtacg atgcggagtc ttcggtattg aaaagccgac tgaaccttgc tctatatttc 120
tcgctgacaa agagaggtga atatctgggt tccttggtaa cggacttgcc aatggatttg 180
ccatcatctt attccgaaat cttagaggct gaagatgatt cctactcaag attggctgaa 240
tcaatgtaca aatgccctaa ctataagcat catggaagac cttgtgcaag gcagttcaag 300
caaggagagc cgatataccg gtgctacgaa tgtggttttg acgagacttg tgtaatgtgc 360
atgcattgtt ttaataggga gcaacatcga gaccacgagg tttccatttc aattgcttcg 420
tcctccaacg atggtatctg tgattgtgga gatcctcagg catggaatat cgaattacac 480
tgccagagtg aactggaaca agatgaccat tcaagttcag aagttaatcc agattttaaa 540
tctgctataa gggaaacaat ggatattatt ttagattaca ttttggattg tactattcat 600
tctgcatcta tgcttcctgc tgttcaggac atgatgaagg aagacccatc cgactatgaa 660
atggctattc aatatgcttc agatagttct tctctgccca ttgaaagata tggagtggaa 720
gacacgaatg ttcagtcctg gaacgtagtc ctgtggaacg acgaattcca taattatgat 780
gaggctattg attgcatcca gcaagttagt agatgttcat tgtctaaagg acaagctgac 840
gctcaaaaga ttaatgattt tggattttcc atcataagaa gaagtgaatc cttgccttta 900
ctgatagaaa ggtgcgccaa ggttgaagaa tccgggttta ctattacgat tctttctgat 960
agagatgtta cccgattgat tattattgat actatttttg attggttatt gactctgtta 1020
gaaatttcaa ggccggaaat tcagactgct attagagaaa gtttgtgtga atctcttttg 1080
gaagagtttc atgccgacat tcacgaagga gattttttct accgggaaga tgaatattca 1140
gacacacggg gtttgctgga tttcaaaaac agaattccag ccccattggt ggaggatgta 1200
atgaacgagt tgtctattga tgacttgaag aacagaaaac tatccagttt tcttaatgaa 1260
caaccttcag ctctagtcgg ctcaagagta cagtatttct tctatatgga tctgcggttc 1320
tggaaaaagg caagaaaatc tttgaaattg ctaacgacat ctgttttggt ttcaaacttg 1380
gaatacaaaa agactttttc tgaacagttt gtgaaaatat actcgcatct gttgatattg 1440
atggcaaagg aagatagaga gtggcttctc agcaatgcgg gcaatgctgt agtacaactc 1500
tttacatgtc ctaaaacatc tctccattta ttacaaccac aatatttcag aagcatcatc 1560
gtccccatca ttttgttgtt cgaatcttat actggaaacc atttgctgtg gaaacgacca 1620
tatcaactct tatcacgtaa gaaaggtctc aaatttggtt taatgcgttc tttaactgat 1680
ctagtgacgt taatcaccac tgcccatcaa tcagaagaac atttggtact ttttcagggt 1740
aagaacttca tttacataat catgcttttt aggatgttcc agagtgccct gacattggtc 1800
agaaaggaag gagaacatat taccagggaa tccactgaat ttttaaccta cctgcaaata 1860
tcttactacc ttaatgatgt catcaaaggt attgttgaaa ttgcgcaggt tcctgaaata 1920
cgtaaacctg aacattggaa agttgtggaa acaaacatac aaatattggc cactttaatt 1980
tcatcagaac cttataagtt tcatatggtg cacgaaaaac aacttattga ccatgacgta 2040
acaaagaaac caacctctct tattaatcca ttgaatggat tactgtctaa catgttaaca 2100
accgtaaggg ccaattcttt ttcattttta actcgtcaag tttctcagat taatttttgg 2160
agtatcaatc ccgaagtctc attttcagat gatttagact atctgaaact ctcatcgaag 2220
agtttagaag caattacttt gagttcacag ataaaaattg gccactggat tagaaatgga 2280
tccatgacta gtaaacaagc gcaattgtac tgcacgaggt tcactcaata tggttacata 2340
gccgacgttc atttgaacca acttgctata ctcgaagaac gcgacgatga tcgtctatta 2400
ttaaacattt tggatagatt caatctaata gattggttct ataacgatca ggacgtgctt 2460
ggtactgttt tcgaagaacg atctttttac ctaatgaatg aattggttaa gtttctttat 2520
aatatgtttt cacacagagt taacttccag tttgaatcaa atttcacaga gaaaacccag 2580
tatgaggtaa cgcaatacat tttatacacg ctttgtaaag gatctttgtc attttcagat 2640
ctgacagccg actttcctat ctccgtggaa gttactgttt ttgacaagat ccttgatgag 2700
gttgctgttt acgaagagcc caaaactatg aatgattctg gaaagtattc tatcaagaaa 2760
agttattaca aaaagatgga tccaatgtct atttatgtgg actcgggtga tttcgatgat 2820
gtatcaacag cgatagtaaa ggaactttca attttaggaa aaataaaaga ggagaatgtt 2880
gtaattgaac ctcagatcag tggaccgaat gaatccaaca gccgtgtctt gagcagattg 2940
aaacggttct tcattagcaa atctgtagtc aaactgtttt ataaattgtt acaatctgct 3000
ctttctgaga gcaatgagac ctacgtcatt gaacttttac atttgattca agcagtttta 3060
ttagatgaac atgaattgta cagaatcgaa gatccagtgc aatactttat tcaaattcct 3120
gtgtgtgatc tactgttatc agttgttgag cacaatgatt tttcacgacc tgtctgcaaa 3180
aaactgaagt tctattgaat tggttgatcc agcgggacga gtcaatcatt gactcattgg 3240
ttgattcttt tggtgaaaag cacattgaaa actttaaaaa atctaaggga tctcaagttc 3300
tggagactaa acgagctaaa caaaagcgtt tagccaagga gagacaagag aagatcaaat 3360
cacgatttgc taaacagcaa aagtctttca tgaagcagaa tttggacgca aaaaagagtg 3420
cggaacatgt aactacacat ttatccaaag acaatgaagg attaggtagt tcctcccagg 3480
actcttttca tgagtgcatt ctttgtcaac gtgctcagga gggcaacgag atgtttggaa 3540
tccctgcata tgttgaaaaa gtttccacgt tttgggattt tcaacctaag gatgagtcaa 3600
cctatacgga aagatgctta acaaccattg aaaatcaaat gaaacaattg catgaagaaa 3660
cggatgccaa caatgaggtt agagaacatc tttattatca aaaagatact cctgtaaaaa 3720
gcatggcacc gatatcttca agacacattg ttaagtcatg cgggcaccac atgcattata 3780
aatgtttttc tgagttacta gaaaacagca ggaagtttag cacttgtccg ctttgtcgct 3840
ctgccattaa tgcttttgtt ccacaatttg ccatgaaaaa cgatgctagc cctgcttttc 3900
aggaggctgc ttcgaatatt agtcactttg aaaagttgaa tttgaatcaa attgtatcga 3960
aatatcttct caatgattcc ttcttgaaat ttattgcgga agaaagtaag gaccagttca 4020
tgtatttgaa tgagtttaaa gacattttga aagacgcccc agatgcttct gaccacatgt 4080
tgagtgaagg gttatttccc tcatttttgg ccatgtcaac attattgggt aataccctag 4140
caaatactga aattcgtctc agattatccc ccgagaagat tccccagaaa ggaaacttga 4200
agagaaaaga ttcggaatta ataacctcat tacttcaatg tgtctcggtt atctcaatct 4260
tattgaaaca atcttatcct gaagagcagt atctgtctcc atttttgaat aaaccaaatt 4320
cattaattat tgattttgcc atttcacttc tacttggaaa agaagactca cttcaagaaa 4380
ctattgtggg catttacaag caaacaattc tgcattcatt gaatttacta ttgactaacg 4440
ttggagataa tgagcatttc agaaggatgc tgagcggtgc aaactctatt attaatgatt 4500
cagaactggc cattttcaaa aagtttgtgt caacggccac ttttacctct gatgtttcat 4560
tcattacttg caacgaacaa ttattggttg gactgtatat tcttttggag aaaaccacca 4620
cagtgtatct taaacagttg tttctgataa tcagcatgtg cagacccttg gacttatgcc 4680
taaatcgtga ctacgagaat tccaatgatt acgaccacta tttgtttggc caactgtgca 4740
aattttttaa cctttccagt ataatcagtt atttgggatc tggaattcct ggtggaaacc 4800
tattggagga gcaaaatgat cttatattaa aaggacaatc cactctccct tcaacaattg 4860
agtatccagg tctcgtttat cttgtgaatt tgcctagaga actgaacact tttacttttt 4920
caaaatatga cacccaagat gcagttaatc taaacttttc tgtttgttta acgtgtggca 4980
aaagagtgaa acatagcggt gattctgaaa atgaaattga aaacttccct gggtacaatg 5040
gtgttcctct tactttgttt caccatcata agaattgtcc tttctctgga tatggagaag 5100
cacaatgtat cttcttaacc ccaaagttga ataaattgac tgccttacta aagattcagc 5160
ctccacgagg aatttctgat cgctcgctat atcacagtac atttgcattc ccattgagca 5220
gcccatatct aaccacacat ggagagtcac attctggtca tggaggcttg atacgcaaag 5280
cgttcctgaa tagagatcga tttcgaaatc tgaatgagct atggttggat ggtgaactag 5340
ctttgtatat ttcccgaagc cttggggatt ctcaaattgt agcggaacca atcaaccctg 5400
ttatgattac aatgccggga ggtattcagg aggcattaaa tcttgcgttc accactttcc 5460
tcggtgacca agaacccggg gatgatgact tggaagatta tgagtatgac atactgttaa 5520
atagatga 5528
<210> 23
<211> 3168
<212> DNA
<213> Pichia pastoris
<400> 23
atgtctgcct ttggtgtggt tccgagtgta ttaaacactg gaaaccagat caagcagaaa 60
aacggaacgc ttttcaagaa atcttctgga gtttacaata aacagcagcg ggatcacaat 120
tccagggata aaaagcgatc agctcgtaaa acaaatacac cgccaacacc gactgagagt 180
acttccgcaa agaagtcatc aactcaatca gacgacaaag tgagtcctga tattttacaa 240
ttgtcgcata ttgagattca atatgtgggc ccacttcttt ccaacccaga atctttggga 300
tatgtgaaac aaaacaataa taccaaaatc aagactccga aatatttagt ggatacagat 360
tcaaacctgg tttttggtcc tgatacaact aataaatggg atattgagaa ccagcacaaa 420
atgatcgaaa tggaatcttc ccatcaaggt gactggcaag gtatttatga acaatttcaa 480
gaaatgaata aagtggagcg tcaaaaaatg gaagatctgg gcttggtggc aaaagaggga 540
caaagcatgg acctgacaaa tgctatctca ttcaaaggta gctgcgtgga tatgtgtccc 600
gtttatgata gagtcaagag ggaggtacag agagatgttg atccattgga gagagatcct 660
gccactggta agatatctcg agagagagct ttaaagaaat ttgtgcgtcc ttcaggccaa 720
gcaccgcctc ttccttctga cgtaagacct cctcatattc tggtaaaaag tttaaactat 780
attgtggata atttgctgga taaattaccg caaagtcatt cattaatttg ggatagaacc 840
cgtagtatca gacaagattt tacactacag agctactctg gcttggaagc aattgagtgt 900
aacgaaagaa tttgtcgcat acatctactt tgtgctcata taatgccggg ttctgatcaa 960
tctgacttct ccaagcagca agaaattgaa caattcacaa aatcattgaa aacattaaca 1020
gacatatatg atgttgtcag atccaaagga ggaaaatgtg ccaacgaagc tgaattcagg 1080
gcttataatt tgctggtgca ttttcgggac ccaaatctaa ttcatgaaat ccagaactta 1140
cctactcgaa ttcttaagga cgaacgagtt caacttgctt taatgtttcg aagtctacta 1200
ttgaataata atttcaaaga ataccagagg aacattcctg gttgcttggg ggtttttcag 1260
cagtttttca atatgtgttt tgatccagcc accccattct taatcggatg tgtgctggaa 1320
cttaattttg aagagataag attttacgct ttgaaatcga tctcacgttc ttatcacaag 1380
aaatctgccc ctctaacgac ccagaagtta gcatctatgc tcggatttga ttccgaggat 1440
aagctcctaa ctttcactaa ttatttcaag actcctacgt gtactaattc tagaaatgaa 1500
acgtgcattg atatctcaaa acttagatac gagagtttta cggatttggc tgctccaaag 1560
cagatttaca cttcaagatt agacaacaaa ttaaaaggat tcacctataa ggatgttgtt 1620
gatcaaggat taaataacac atccttgcac atagctaatt tgaaagaaac aatggctcag 1680
aatcaacata ttgcagtgga gaaattaccc aatatctcat ttccacaaca tgctttgtct 1740
tctacccctt tcgaagtaga atcaaagtca gacatagtca gatcttcttc cggatcggct 1800
ccgccccaga ctttgatccc accgattcaa gaaaaagtaa taacttctca aatacagcca 1860
ccaataactc ccgtcgttcc cactgaagaa atccaaactc ttccaaaaat agaggagccc 1920
aggttcaaag atcttccaaa ttttgaaaat gcatgcaaag aggtttcctc tattttaatc 1980
aagaagacta tatctccttt gattgctccc atagtgaaca atcagctaga agagtacaac 2040
cggcgacaaa cggttttaag ggatcaggag agacaaaatc aaagaagaca acttttgatt 2100
tcatcccttc aggaagaatt gtactctgct tttatacgag aacaagtgta tattcaagtg 2160
gttgatactc aagccaaaga gtgctttaac aagaatctga aacggcgaat atttcagaaa 2220
ttcatcgggg gtttaattac attgaaaaac aaacaaatga ataagagaag aaaacttgat 2280
gaaattcaag tcttcaagaa taaggttgtt tcctcaagtc aacttcggta ttcagtttca 2340
agaagtcaaa cggaggacaa ttcaacgtca aactcgagtg acgaggaagc atcagctgtt 2400
cagatgaata ttactctttc accatctgtg gatccacttt ggtcacccat agatattaag 2460
tttatattag actccaattt aaagttgttt gaggataaca aggataaata ctggaatttc 2520
atgtttgcga ttgccgattg gactattcta ccaagcaaat ggcttcgtta caaattccaa 2580
cttcaaaacc ccagtctcat aaatactgtt gaatcctcaa attacaaagc caaattacgg 2640
gctctaccca gtgacaaact tcttacaagg gaatacatgg agcactgtcg atttttggta 2700
tttcaagtcg gaaaggttga tgaatcatca aacctgaaag aatctttgtt cagagactca 2760
cagtttatta accgattaat gaaatatgcc aagaagtact cgcaatacca gattggagta 2820
cttgtcttat attatcatga ggatgactct tttgataaac agaaaattat tgatcttttg 2880
ttattagaac aatacacaaa taagttagtc aactcactcg agatagttga catgaacaaa 2940
ctcacaaatg atgaactgat aaaagcattg accacgctag tccacaacta taaggataaa 3000
ggtatcaaca aatcggtacc aacatcttcc accaaaggac acaccactag cattatggaa 3060
caggatatga cagtatacag ctacagcacg tccaattcca gggatgctaa gcttaattat 3120
attttgaagc aagcctaccc ccgcaggggg tttcacttga aacaatga 3168
<210> 24
<211> 1401
<212> DNA
<213> Pichia pastoris
<400> 24
atgtcagaat ggccctcagc tttggaaaat tttgtaagtc attgtttcca gcgtgccaac 60
attgagagct ttccacccgg caaaaaaaaa gaactccaaa aacagttgac gcaaatcatc 120
aatttagcaa ttcttgaaaa caaacttaat tctaataact ggtccaaaca aaagctacca 180
atatttggag aagcaagaga gttagaattg gagcagaaaa tgggaaatgt ttatccaatt 240
actgtttcta gtcgaagaag tgacttgatg catcaagagg cagttcaacc atctgagcct 300
ttagttccct ccgaaagcca acaaaagaaa aagtctagag aattgcgatt taagatcact 360
aaaaaaagtt ctgtatcacc cgcaaataaa atacaagttg cttgtgactt gaattgtaaa 420
cttgtgggaa ctaacacctc tatcgagaaa gattattata gacttacatc tcatccggat 480
ccttccatgg taagaccttt gcctatttta aagaaatcgt tgcagcatct ttacgccaaa 540
tatcaaagtc tagaacgttt caaagctctc agcaaggcag agtacagcta ttttttgaat 600
caactgaaat ccctaaggca agacctcaca gtgcaagaca ttcagaatca gttcactgtt 660
aaagtttacg aatttaatac tcaattggcg attcaaaatg aagattttgg tgagcttaat 720
caatgtttga ctcagctggc gcaattgtac actgtatcaa ctatgggtca tacttattac 780
tattctgata ctggcaaata caaccaagag cacaactgtt ttcttgccaa ggatctttgt 840
gaggatcgaa accatatcaa tatgttcaaa tttacgagtt atagaatttt atattttctt 900
ctcatagacg ccccctggga attgctaaaa ataaggcagg atttattcaa ccgtggtcaa 960
cagtatgcaa ttcgtcacaa caaatttctt ttgaagtcat tcaagctttc ggatctcata 1020
accgccatgg attatattca tatcaaggac gaatattcat tcctcgtgaa tatggactca 1080
gatgtctgca atttaaggac agtgtttgat gacgaacata tgactttgaa ccaagacgac 1140
tggtttttct ataagatact ctaccataag attttcttac gagaacagct gaaggccctg 1200
ataactataa gcaaatctta tcgacagata tccctctact acttgaaaaa tctactgatg 1260
gatttagtat tcttggaaaa gaataagtta tctcgtttca ttgagaatgg tgaggtattt 1320
aactgcacga gcgcaagatc attactgctt caaatagaga agaagcagct atcaaagata 1380
gatatcaagg gtcaggtatg a 1401
<210> 25
<211> 1075
<212> DNA
<213> Pichia pastoris
<400> 25
atggttgact cagagactat caacaaattc atagaagtaa cgggagcctc tgccttccaa 60
gcaattcagt acctagagga gactgatgac tttgaagcgg cagtcaatga ttattattcc 120
tctcaactgg agaatgagaa gggcaagggt aaatcagaac gtccagtcaa tcaaacaaag 180
gcttctgcag ggcccaagat cagaactttc aacgacctaa atagcaactc aaatggggac 240
aacaatcttt tcacaggtgg tgaaaagtcc ggtcttcaag ttgagaaccc agacaaacgt 300
ggggaccctt ttgggttggt caatgatctt ttgaagaaag ctgaggaaac tggccaacaa 360
ccagatacaa ggccccatga agaagctcct gctagacaat ttgttggaac tggccacaag 420
ctgggcagta cggacagtcc ctccgaagtt agtgtctgac cctgcctcaa gaataagaag 480
agctcagaaa gtcagccgac agataacatt ttggaaggac ggattccaag ttggagacgg 540
agatttatac agatatgatg accctgcaaa cgcaagatat ctagccgact tgaacgctgg 600
aagggcacca ctggctcttc tagatgtcga gattgggcaa gaggtagatg tcacagtgca 660
taaaaagata gaaaaaaatt tcactcctcc taagaaagcc cgagttggct ttcaaggtaa 720
aggtcagaga ttagggtctc cagtaccggg cgacataaag ctcagtcaat ctcctgaggt 780
gcaacaagaa acacaagagg aagctgagga ggaaaagcaa aaggaggagg ccgagcagct 840
gggaactggg gattctcccg ttcagattag actcgccaat ggtcagagaa ttgttcatag 900
attcaattct actgattctg ttgctcaatt atatgcattt gtcaatgaac atagtccctc 960
cgccagagaa tttgtgcttt ctctagcttt cccggtgaaa cctattgaga acaatgagga 1020
cacactcaag gatgctggac tcataaacgc tgttgttgtc caaagatgga aataa 1075
<210> 26
<211> 897
<212> DNA
<213> Pichia pastoris
<400> 26
atgggcgtga tacttccaga cgatggtaag caatcgggag gccaaccaaa tagaagggct 60
aaagtcctga gccgattttt accaccagaa catcaaagac cttcaatcgg cctcttcctg 120
ggacctttta ctccagcagc tgataatgag attgccctgt ggacttgcat tggcgctcag 180
ctctttagtg ggctggcatt gcttagaatg agccgaagat ttgttttttc gcccgatcaa 240
tctgtaagaa ggtttctctt taagactttt cataatgtgg taggtgcagc cctgatattt 300
gggagcggat tagaagggac taggatgctt ctacctgagg atccttggaa agaagaagct 360
agaaaagcaa gaatattggc ccaattgaaa ggtgagcccg ttagttggtg gtatggaccc 420
aagagtttta ttccttctgg aaggttagaa tacacaaaac agatgcagtt tcacaacttt 480
gaagtcatgc ataaatcacc cgaaaaaata gcccgagctc tcatgattaa ggacaaactc 540
aaggaggaaa caaataccct ttattcgtcc attcatgaga aagcggaaca acagactatt 600
cgactctcta aagatctaca gaacaacgtt cccctcaaag gggtaacgtc atatgttcct 660
caatttagca cttcaaatac ggacaccaag ttatatttga aaaatgttag cttgaagacc 720
catgccgacc tggaaaaggt ctgggcagaa cacaatcctt gggacatcct ggaagagaaa 780
atttctccaa tttccgtaat tgcactgcca aagtttaacc caattatatc tgaggttgaa 840
cctgacaagc agcaaccatc tacgggtgat atcaaataca ttagtgacag aaaataa 897
<210> 27
<211> 1530
<212> DNA
<213> Pichia pastoris
<400> 27
atgaaatatt tgccactcgt tgctaccctg gcctcttcgg ccctcgctgc tggcatcaac 60
ttcgcccaat tactggacca gaagccactg gacattgccg ataatgttaa atgggaattg 120
aagcctgagg tcgactctgc tgctcttcaa agtgcagtca atgagctaga cttgaaaatc 180
gaagccagct atttgtttaa agttgcacat ggttccgtct ttgaatacgg acatcctacc 240
agagtcatcg gttctcctgg tcactggtcc acaatcaacc atgtcctcga cacattacat 300
aacttcaaac actactacga cgttgacgtt cagccatttg aagcctttac cggtatcctt 360
aagtctttct cattgaccat taacggagtt gcaccaaagt ctgcagaagc tttagattta 420
actcctccta ctcctggcgg ttttccagtg accggtccag tcgttttagt tgataattat 480
ggttgtcaag cttctgacta tccattcaac gtgactaacg gaattgcctt aattcaaagg 540
ggttcttgtt cattcggtca aaaatcagaa cttgctggtc tccgtggagc caaagccgct 600
ctcatttaca acaacgtgcc aggtagtgct aagggaacct taggtgcccc aactcctcat 660
caggtaccat cgttgtcact ttctcaggaa gatggagagg ccgtcaagcg tcagcttctg 720
acttctggaa gcgtaattgc aactgtcgct gtcgattcct acgttaagaa gttcaaaacc 780
aagaatgtga ttgctaccac tcgttacggt aatgatagca acattgtgat gctaggtgca 840
cattcagact ctgttgctgc tggaccaggt atcaatgacg atggttctgg taccatctct 900
cttttgaacg tggccaaata cctaactaaa ttcaaagtta ataacaaggt tcgtttcgct 960
tggtgggcag ctgaagaaga aggattactt ggatccgact actacgtttc aaagttaacc 1020
cccaaggaga aatctcagat tcgtttgttt atggactacg atatgatggc ttcccctaac 1080
tacgcctacc aggtctataa tgccactaac agcgagaacc cagttggatc tgaggagctt 1140
aagaatttat acattgactg gtacgttgaa cagggtctga actacactct agttccattt 1200
gatggccgat ccgactatga tggattcatc aagagcggta ttcccggagg tggtattgct 1260
accggagcag aaggtttgaa gaccgaagag gaggctgaac tatttggtgg tgaagctgga 1320
gttgcatatg acccatgtta ccactctctt tgtgacgatt tggccaaccc tgactatgtt 1380
ccatgggttg tcaatactaa attaattgcc cacagtgtcg ccacttatgc aaagagcttg 1440
gacggattcc cattgcgtga ggagcctagc ccattcaaga tgactgccca gtcaaacttc 1500
aagtaccacg gtccaaaact tgtcctttag 1530
<210> 28
<211> 513
<212> DNA
<213> Pichia pastoris
<400> 28
atgctcaaac actccttaaa aacagggttg gtctttctca cttggatacc ggtgatttat 60
acggtaaagg aacacctgat atacgttgga aaggtggaag gatcctcaat gtcacccact 120
ttgaatcccg ttaaaggtta ttctgactat gtgattttat ggaagttaaa cttcaaagag 180
tcactcaaag tgggagacgt ggtttttata aggtctcctg tagatccaga gaagttatat 240
gctaaacgta taaaggctgt tcaaggggat accgtggtga ctaggcatcc ataccccaaa 300
gacaaagtgt ccattccaag aaaccatctt tgggtagaag gagacaatat acacagcgtg 360
gatagtaaca actttggtcc gatatcgttg ggccttgtat taggaagagc aactcacgta 420
atttttcccc tgaacaggat aggtaatatc tctggtgaag ggggtagaga agttagggag 480
gattatttaa gagcggagga cagtccgatg taa 513
<210> 29
<211> 915
<212> DNA
<213> Pichia pastoris
<400> 29
atggtttctg aaattcagct tagattagct gttattattt atgatatact ctgttcggcg 60
tcttatgttc tagtcatcca tttgagacca accagagccc ttccgcatca acccatagac 120
cgtaacaatc ctctaacgat taaagaaagg tgccagcgag ccagtgtgtt gactgctaca 180
catgtattat tattgcctat tcttttaaaa gtgttgagac tgtcagaaat tgcggaaact 240
acggcgaaac ttggaatagt ggtgggatat cacaaccaga gctggtcttt ctctaacctc 300
caagatgata ttgtcagcat tttcaaagct ttaggtttga ccatgattct cttttctggt 360
cctattgtag attattttta ctattcaaac tcaacagaag taatcaagca agatctggcg 420
tatgtcgtta gcctcgaggg tatgcgtgat ctacttgtgg gacccatcac tgaggaactt 480
ctttatcggt catgttccat ttcattaatg ctagtagcta acgattacgc caacaaattt 540
ctgttcggcc aacactggtt aataatggta tcatcactct acttcggtat agcacatctt 600
catcatgctg ttgaactgta tcattgtaaa agatattcat taactaccat aaccatatca 660
actgccttcc aatggtcata tacaacgtta tttggaatat atgcaagctt tctatacttg 720
cgaacaggat ctgtatggtc agcaatagtt gttcattcat tttgcaacat gatggggttt 780
ccccggttga catttggacg tgatgaagcg agagattgga aagtgggtta ctatgtgttg 840
ctcgctctag gttccgtcct attcaaaaag tttctttact ctctaacaga atctaaccat 900
acgcttcttc tataa 915
<210> 30
<211> 2451
<212> DNA
<213> Pichia pastoris
<400> 30
atgtatcccg aacacaagta tcgggagtat caacggaggg tgcccttatg gcagtactcc 60
ctgttggtga ttgtactgct atacgggtct catttgctta tcagcaccat caacttgata 120
cactataacc acaaaaatta tcatgcacac ccagtcaata gtggtatcgt tcttaatgag 180
tttgctgatg acgattcatt ctctttgaat ggcactctga acttggagaa ctggagaaat 240
ggtacctttt cccctaaatt tcattccatt cagtggaccg aaataggtca ggaagatgac 300
cagggatatt acattctctc ttccaattcc tcttacatag taaagtcttt atccgaccca 360
gactttgaat ctgttctatt caacgagtct acaatcactt acaacggtga agaacatcat 420
gtggaagacg tcatagtgtc caataatctt caatatgcat tggtagttac ggataagaga 480
cataattggc gccattcttt ttttgcgaat tactggctgt ataaagtcaa caatcctgaa 540
caggttcagc ctttgtttga tacagatcta tcgttgaatg gtcttattag ccttgtccat 600
tggtctccgg attcttccca agttgcattt gtgttggaaa ataacatata tttgaagcat 660
cttaacaact tttctgattc aaggattgat caactaactt atgatggagg cgaaaacata 720
ttttatggca aaccagattg ggtttatgaa gaagaagtgt ttgaaagcaa ctctgctatg 780
tggtggtctc caaatggaaa gtttttatca atattgcgaa ctaatgacac ccaagtgcct 840
gtctatccta ttccatattt tgttcagtct gatgctgaaa cagctatcga tgaataccct 900
cttctgaaac acataaaata cccaaaggca ggatttccca atccagttgt tgatgtgatt 960
gtatacgatg ttcaacgcca gcacatatct aggttacctg ctggtgatcc tttctacaac 1020
gatgagaaca ttaccaatga ggacagactt atcactgaga tcatctgggt tggtgattca 1080
cggttcctga ccaagattac gaacagggaa agtgacttgt tagcatttta tctggtagac 1140
gctgaggcta acaatagtaa gctggtaaga ttccaagatg ctaagagcac caagtcttgg 1200
tttgaaattg aacacaacac attgtatatt cctaaggata cttcagtggg aagggcacaa 1260
gatggctaca tcgacaccat agatgttaac ggctacaacc atttagccta tttctcacca 1320
ccagacaacc cagaccccaa ggtcattctt acgcgtggtg attgggaagt cgttgacagt 1380
ccatctgcat ttgacttcaa aagaaatttg gtttacttta cagcaaccaa gaaatcctca 1440
atagaaagac atgtttattg tgttgggata gacgggaaac aattcaacaa tgtaactgat 1500
gtttcatcag atggatacta cagtacaagc ttttcccctg gagcaagata tgtattgcta 1560
tcacaccaag gtccccgtgt accttatcaa aagatgatag atcttgtcaa aggcaccgaa 1620
gaaataatcg aatctaacga agatttgaaa gactccgttg ctttatttga tttacctgat 1680
gtcaagtacg gcgaaatcga gcttgaaaaa ggtgtcaagt caaactacgt tgagatcagg 1740
cctaagaact tcgatgaaag caaaaagtat ccggttttat tttttgtgta tggggggcca 1800
ggttcccaat tggtaacaaa gacattttct aagagtttcc agcatgttgt atcctctgag 1860
cttgacgtca ttgttgtcac ggtggatgga agagggactg gatttaaagg tagaaaatat 1920
agatccatag tgcgggacaa cttgggtcat tatgaatccc tggaccaaat cacggcagga 1980
aaaatttggg cagcaaagcc ttacgttgat gagaatagac tggccatttg gggttggtct 2040
tatggaggtt acatgacgct aaaggtttta gaacaggata aaggtgaaac attcaaatat 2100
ggaatgtctg ttgcccctgt gacgaattgg aaattctatg attctatcta cacagaaaga 2160
tacatgcaca ctcctcagga caatccaaac tattataatt cgtcaatcca tgagattgat 2220
aatttgaagg gagtgaagag gttcttgcta atgcacggaa ctggtgacga caatgttcac 2280
ttccaaaata cactcaaagt tctagattta tttgatttac atggtcttga aaactatgat 2340
atccacgtgt tccctgatag tgatcacagt attagatatc acaacggtaa tgttatagtg 2400
tatgataagc tattccattg gattaggcgt gcattcaagg ctggcaaata a 2451
<210> 31
<211> 1866
<212> DNA
<213> Pichia pastoris
<400> 31
atgaaaccgt atcaccatgc aaaaagccgc ccaataggca gctacctgta ttttggggtg 60
tttaccgtag cattgacatt tctgacgtgg cttaaatatg acgcagagct gtttgctcag 120
caggttcact cgaaagacat ttatgaccca cagttcaaca ttacgttgcc aattgatggc 180
ccaacattta ccccatcaaa gaactattca attagtgttc aaaatgcagc agtggcgtcc 240
gatatagaac aatgttcaaa attaggtgta tctattctgc agcaaggtgg caatgcggcc 300
gattcagcag tcaccgtggc cctgtgtatc ggaacaatca attcgtattc gtccggtata 360
gggggaggag gattcattgt ctctaagtta attgataatc ctaccgctct gagttttgat 420
tgtcgagaaa tggctccttc taaaagtttc aaagaaatgt tcaactatca tgaggagaag 480
gccagagtag gtggtttggc tgtcgccatt ccaggagagt taaagggact ctatgaactg 540
tttcagcacc atggttctgg taatgttgag tggaaagatt tgattttgcc cgttgctgag 600
ttggctgagg tgggatggac tgtcgatccg ctgttttcta gtgcattgaa atctattgag 660
caccatattt acgagcattc atatgattgg gcctttgcat tgaatgaaga cggaaaaatt 720
aaaaaaagag gtgactggat taatcgtccc atgttggcta ctacgttgag gagaatagct 780
gaaagtggca acgttgatct attctatgac ccagagagcg atatagtaca aagcatggtg 840
aatgctacta gaaagtatgg aggaatcctt gaagcctcag actttgcaaa atatagagtt 900
cgaattgaag aatcgttgac attgcataac tttacatctg acggccttac ggtttatacg 960
tccaatgggg catcctcagg gttggtgctc cttgctgggt tgaagctcat ggacttattc 1020
gaagatttca aggaatttca taatgatttc ggggctgttg agtctcaaag gcttgttgaa 1080
acgatgaagt ggatggcttc agtaagaagc aaccttggag atttgaacat ttactccacc 1140
aacgaaactg aaattgacga tcataggaag aggtacgaca gatacaaatc agatgagtgg 1200
gcaatagaaa ctcatgccaa aattaatgat tcccacacac ttccttcttg gaaagattat 1260
gctccagcct ttctacctaa tgatcctcat ggtacatctc atttcagtat cgttgaccaa 1320
tacggtaatg cggtggctat gacaaccact gttaaccttg gatttggatc taaaatacac 1380
gatcctatat cagggattat tctaaatgat gaaatggacg atttttcagt tccaacatca 1440
tctaatgcat ttggtttgca tccatcaatc tataattggg tagagcctta caaaagacct 1500
ctctcttcat gtgctcctac cgtaattgtt gattctctgg gagtacctca ttttgtcatc 1560
ggggcagcag gagggtccaa gatcactacc acagttttac aagcaattat aagagtttac 1620
cattatcacc tggatctttt agacgtcatt gcatatccac gctttcatca tcaactactt 1680
ccggaagaag ttcttctgga gtttccacga gataataaac taatacgcca tctaaaagaa 1740
agagggcatg atgttagagt ccaagcacca atatccacca tgaatggtat cctacgaaaa 1800
agaggtggaa gcctgatagc agttagtgat cactggagaa agcttggtcg accttggggc 1860
ttttga 1866
<210> 32
<211> 1605
<212> DNA
<213> Pichia pastoris
<400> 32
atgaaatcgg ttatttggag ccttctatct ttgctagcat tgtcgcaggc attgactatt 60
ccattgctgg aagagcttca acagcaaaca ttttttagca agaaaaccgt tcctcaacaa 120
gttgctgaat tggtgggcac ccattactct aaggatgaga taatcagtct atggaaggac 180
attgagctgg atgtacccag ggaaaagatc caagaggcct tcgataagtt cgtaaaacaa 240
tcaactgcca cttcccccgt tagaaatgaa tttcccttgt ctcagcaaga ttgggtgaca 300
gtgaccaaca ccaagtttga taattatcaa ttgagggtta aaaaatccca ccctgaaaag 360
ctaaacattg ataaggtaaa gcaatcttcg ggatacctgg atatcattga tcaagataag 420
catcttttct attggttttt tgaatcccga aatgatccgt ccacagaccc aatcatccta 480
tggttgaatg gtggacccgg ctgctcttct attacagggt tgctattcga aaagattggc 540
cccagttaca tcaccaaaga gattaagccg gaacataatc cttattcatg gaacaacaat 600
gctagtgtta tcttccttga gcaaccggtt ggagtaggat tttcttactc ttctaagaaa 660
gtcggtgata ctgcaactgc tgccaaagat acatatgtgt ttttggagct tttcttccaa 720
aagtttcctc agttcctgac ctctaatctg cacattgctg gggaatcgta tgctggccat 780
tatttgccca agattgcttc tgagattgtg tctcacgcag acaagacgtt tgacctttca 840
ggagtcatga tcggtaatgg tcttactgat cctctaattc agtataagta ctatcagcca 900
atggcctgtg gaaaaggtgg ctacaagcag gtcatttcgg acgaggaatg tgatgaattg 960
gatagggtct atccaagatg tgaacgttta acgcgggcat gttatgagtt ccaaaattca 1020
gttacttgtg ttccggcaac actttattgc gaccaaaagc tactgaagcc gtacactgac 1080
actggcttga atgtctatga tattcgtaca atgtgcgatg aagggactga tttgtgttac 1140
aaagaactgg aatacgtgga gaagtacatg aaccagcctg aagtgcagga agccgtgggc 1200
tctgaagtca gttcttacaa aggttgtgac gatgatgtct tcttaagatt tttgtactct 1260
ggcgatggat ctaagccttt ccaccagtat atcacggatg ttctcaatgc aagtattccg 1320
gttctgattt acgcaggtga taaagattat atctgtaatt ggctaggaaa ccaagcttgg 1380
gtcaatgagc tagaatggaa cttgtctgag gaattccagg caactccgat tcgaccgtgg 1440
ttcactttgg acaataacga ttatgcagga aacgtacaaa cttatggaaa cttttccttt 1500
ctaagagtat ttgatgctgg tcacatggtt ccttacaatc aaccagtcaa cgcacttgac 1560
atggttgtca gatggacaca cggtgatttc tcatttggtt attaa 1605
<210> 33
<211> 2520
<212> DNA
<213> Pichia pastoris
<400> 33
atgactcaat tagatgtcga atcattgatt caagaactca cactaaatga aaaggttcaa 60
cttctgtccg gatcagactt ttggcacacc accccagtta gacgtctagg aattccaaag 120
atgagattat ctgacggtcc taacggcgtc cgaggaacca agtttttcaa tggagttcca 180
accgcatgtt ttccttgtgg tactggatta ggtgccactt tcgataaaga acttctaaaa 240
gaagctggct ccttgatggc agacgaagct aaagcaaaag ctgcctcggt agttttgggt 300
cctacagcta acattgctcg aggccccaac ggaggaagag gcttcgaatc ttttggagag 360
gatccagtgg ttaatggatt atctagtgct gcaatgatta atggattgca aggtaaatat 420
attgcggcta ccatgaaaca ttatgtttgt aacgatttag agatggatcg taattgcatt 480
gatgcacagg tgtctcacag agctctaaga gaagtgtacc ttcttccatt ccaaattgcg 540
gtaagagatg caaatcctcg cgctatcatg actgcttata ataaagcaaa cggtgaacat 600
gtatctcagt caaagtttct tctagatgag gttttgagaa aagaatgggg ctgggatggt 660
ttgttaatgt ccgattggtt cggtgtgtac gatgcaaagt cttctatcac taatggtctt 720
gacctggaaa tgcctggtcc acctcagtgc agagtccatt cggcaaccga tcatgccatc 780
aattctgggg agatacacat aaatgatgtc gatgagcggg tgcgaagcct cttaagttta 840
attaactatt gtcaccagag tggcgtcact gaggaggatc cggagacatc cgataacaac 900
accccagaga ccatcgaaaa actcagaaaa atcagtagag aatcaatcgt cttgctgaag 960
gatgatgaca ggaacagaag tatccttcct ctgaagaagt cagataaaat tgccgtgatt 1020
ggaaacaatg ctaagcaggc tgcatattgc ggaggaggtt ctgcttctgt tctctcgtac 1080
catactacaa ctcctttcga ctctatcaaa tcacgattgg aagattcaaa cactccagct 1140
tacaccatcg gtgctgatgc ttacaagaac cttccgcctt tgggccctca gatgacagac 1200
agcgatggaa aaccggggtt cgacgccaaa ttttttgttg gctcgcctac atctaaagat 1260
agaaagctga ttgatcactt tcagttgacc aattcacaag tcttcctggt tgactactat 1320
aatgaacaga tccctgaaaa caaagagttt tacgtagacg ttgaagggca attcattcct 1380
gaggaagatg gaacctataa ctttggcttg accgtattcg gaacgggaag attattcgtg 1440
gatgataagc tggtttccga tagtagccaa aaccagaccc ctggagattc cttttttgga 1500
ctagcagctc aagaggttat cgggtccatt catttggtca agggtaaagc atataaaata 1560
aaggttcttt atggatccag tgtcaccaga acatatgaaa ttgcagccag tgttgctttt 1620
gaaggaggag catttacttt tggtgcagca aaacaaagaa atgaagatga agaaattgct 1680
agagctgtgg aaattgctaa ggcaaatgat aaagtggtgt tgtgcatagg tctaaatcaa 1740
gactttgaaa gtgagggatt cgacaggccg gatatcaaaa ttcctggagc aaccaacaag 1800
atggtaagtg ctgttttgaa ggctaaccct aacactgtga tcgtcaacca aacaggaacc 1860
ccagtcgaga tgccatgggc cagtgacgct ccagtgatct tgcaggcttg gtttgggggg 1920
tctgaggcag ggaccgctat agctgatgta ctattcggtg actacaaccc tagcggaaaa 1980
ctaacggtta cttttccctt gagatttgag gataaccctg catatctcaa cttccaatcc 2040
aataagcaag catgttggta tggggaagac gtttatgtgg gctacagata ttacgagacc 2100
atagacaggc ctgtgttatt cccatttggc cacggattgt cattcaccga atttgatttt 2160
accgacatgt ttgtcaggct tgaagaagaa aaccttgaag ttgaggttgt agtcagaaac 2220
acaggaaagt atgatggtgc tgaagttgtg cagttgtacg tagcaccagt atccccatcc 2280
ctgaaaaggc ccatcaaaga actcaaggaa tatgctaaga ttttcttagc cagtggtgag 2340
gcaaaaacag ttcacctgag cgttcctatt aagtatgcca cttcgttctt tgacgaatat 2400
cagaagaaat ggtgctccga gaaaggagag tacacaatct tactgggatc cagctcagca 2460
gatattaaag tttcgcaatc tattacttta gaaaaaacaa ctttttggaa aggtttatag 2520
<210> 34
<211> 5004
<212> DNA
<213> Pichia pastoris
<400> 34
atgttcctca aaagtctcct tagttttgcg tctatcctaa cgctttgcaa ggcctgggat 60
ctggaagatg tacaagatgc accaaagatc aaaggtaatg aagtacccgg tcgctatatc 120
attgagtatg aagaagcttc cacttcagca tttgctaccc aactgagagc tgggggatat 180
gactttaaca tccaatacga ctactcaact ggttcccttt tcaacggagc atctgttcaa 240
atcagcaacg ataacaaaac cactttccag gatttgcaaa gtttgcgtgc agtcaaaaat 300
gtttacccag ctactctcat tacattagat gaaacatttg agcttgctga cacgaagcca 360
tggaaccctc atggaattac cggtgtcgat tctttgcatg agcaaggata tactggtagt 420
ggtgttgtta ttgcagttat cgatactggt gttgactata cacaccctgc tctgggtggt 480
ggtatcggag ataatttccc tatcaaagct ggttatgatt tgtcttccgg tgatggtgtc 540
atcacgaatg atcctatgga ttgtgacggt catggtacct ttgtatcctc catcattgtt 600
gcaaataaca aagatatggt tggtgttgca ccagatgctc agattgtcat gtacaaagtg 660
ttcccctgtt ctgatagtac ttcgactgac atagttatgg cgggtatgca aaaggcctat 720
gatgatggtc acaagattat ttcgctatca ctgggatctg actcggggtt ttccagtact 780
ccagcttcct taatggccag caggattgct caagacagag ttgttttggt ggctgctggt 840
aactctggag aacttggtcc attctatgcc tcctcccctg cttctgggaa acaagtcatt 900
tcagttggat ctgttcaaaa cgaacaatgg acaacctttc cagtaacctt tacctcttca 960
aacggtgaat caagggtttt tccttacctc gcttacaatg gtgcacagat tggatttgat 1020
gccgagcttg aggttgattt taccgaagaa agaggatgcg tctatgaacc agagatctcc 1080
gcagataatg cgaataaagc tattttgtta agaaggggcg tcggctgtgt tgaaaacttg 1140
gaattcaatt tattgtctgt ggctggttac aaggcttact tcttgtacaa ctcattttca 1200
agaccatgga gtctcttgaa tatttctcca ctgattgagc tagacaacgc ttactctctt 1260
gttgaagagg aagttggaat atgggtgaaa acccaaatcg acgccggtaa caccgtcaag 1320
ttaaaggtga gcacgagtga ccaaatgttg ccatctgata aagagtattt gggagttgga 1380
aagatggatt attactcctc tcaaggacct gcttatgagc ttgaattttt cccaacgata 1440
tccgctccag gtggagacag ttggggcgct tggcccggtg ggcaatacgg tgttgcctca 1500
ggaacaagtt ttgcttgccc ctatgttgca ggtcttacag ctctttatga atcgcagttt 1560
ggaattcaag atccccagga ctatgtgaga aaattagtct ccacagctac cgatcttcaa 1620
ttatttgact ggaacgcagt gaaacttgag acctctatga atgctccact tattcaacag 1680
ggagctggtc tagtgaacgc tcttggtttg tttgagacta agactgtgat cgtgtctgct 1740
ccttatttgg agctcaatga caccatcaat agagccagtg agtataccat tcaaattaag 1800
aatgagaact ctgagactat tacctatcaa gttgttcacg ttccgggaac tactgtctac 1860
tctagatcag cttctgggaa catcccatac ctggtcaatc aagattttgc accttacggt 1920
gatagtgatg ctgcgacagt tgctctatcc acagaagagt tggttttggg accaggagaa 1980
gttggtgaag tcactgtgat cttctctaca gaagaaattg atcaagaaac tgctccaatt 2040
attcagggta agattacatt ttatggtgat gtcataccga ttgctgttcc ttatatggga 2100
gttgaagttg atattcattc ctgggagcct ctcattgaga ggcctttatc agtgagaatg 2160
tatttggatg atggttcctt agcatatgtt gatgatgatc ctgattatga gttcaatgtg 2220
tatgactggg attctcctag attttatttt aacctgagat atgcaaccaa agaagtatcg 2280
attgacttgg tgcaccctga ttatagcatt gagaacgact acgaatggcc tttagtttcc 2340
ggacacaaca actattatgg tcccgtggga tacgactacg attatacctc gggtcaagcc 2400
tttttgcctc gttactttca acaacgtatt aacgaacttg gatatctttc tttttccaga 2460
tttgctaact tttctgtagt tcctgctggt gaatacaaag ctctatttag agttttgcta 2520
ccatatggag acttttggaa caaagaagac tggcaattgt ttgaatcccc agtgtttaac 2580
gtcctcgctc caccgaatga agaaaacact actgaagagc caactgagga atccagcgag 2640
gagcctaccg aagagtcaac gtctgagtca actgaagagc cctcttctga gtcaactgag 2700
aaatctagcg aggtgccaac tgaagaaatt actgaagatg caacatccac aattgatgat 2760
gatgaagcat ccaccgaaag ctctactgaa gaaccaagtg ctcagcccac cggtccttac 2820
tctgatttga ctgtcggtga ggccattacc gacgttagtg tcaccagttt gaggacaact 2880
gaagcatttg gatacacttc cgactggttg gttgtgtctt tcactttcaa cactactgac 2940
agagatatta ctctcccacc ttacgctgtt gtacaagtaa ctatcccaaa tgaacttcaa 3000
ttcattgctc atccagaata cgccccatac cttgagccct cattgcaagt tttctacact 3060
aagaatgaaa gattaattat gactagtcag ttcaactacg acaccagagt catcgacttc 3120
aagtttgaca atcgagacca agtaataact caagtggagg gagttgttta tttcacgatg 3180
aaactagaac aagatttcat ttctgcattg gccccaggtg aatacgattt tgaatttcat 3240
acatccgttg attcttatgc ttcgaccttt gactttattc cattgattag atccgagcca 3300
atcaaattga tagcaggtgc accagacgaa gttgaatggt ttattgatat tccaagtgca 3360
tacagcgatt tggcaacgat agatattagt tctgatatcg atactaatga taatttgcag 3420
cagtacttct atgattgctc aaagctcaag tacactattg gaaaagagtt tgatcagtgg 3480
ggtaatttta cagctggatc agatggtaac caatacagca ataccaccga tgggtatgtt 3540
ccaattactg attctaccgg ctctccagta gctgaagttc aatgtttaat ggaaagtatc 3600
tcattgagtt tcacaaatac tcttgctgag gatgaagtat tgagagttgt tcttcactct 3660
tctgcgttta gacgtggttc attcaccatg gccaacgtgg taaacgttga cattacagct 3720
ggtggattgg caaaaagaga actcttctct tatatattgg atgaaaatta ctatgctagt 3780
actggatctg aggggttggc atttgacgta tttgaagttg ctgatcaggt cgaggagcca 3840
actgaggagt caacctcaga ggaatctact gaacaggaaa cttccaccga ggaacctacc 3900
gaggaatcaa ctgaacctac tgaggaatct acccaggaac ctactgaaga gcccaccgac 3960
gagcctactt ctgagtcaac tgaggaacct tctgaggagc caacttctga cgatctctca 4020
attgacccaa ctgctgtacc taccgatgaa cctactgaag agccaactga ggagcctact 4080
tctgagtcaa ctgaggaacc ttctgaggag ccaacttctg acgatctctc aattgaccca 4140
actgctgtac ctaccgatga acctactgaa gagccaactg aggagccgac ctctgagact 4200
accgatgatc catcgatagc acctactgct gtgccaactt ccgacacatc ttctggacaa 4260
tcggtggtta ctcaaaacac tacagtcact cagactacca tcacttcagt ctgtaatgtt 4320
tgtgctgaga cccctgtaac aatcacttac actgcaccag ttgtgactaa gccagtttct 4380
tacaccaccg ttacttcagt ttgccatgta tgtgcagaga caccaatcac agttaccttg 4440
acgttgccat gtgaaaccga agacgtgaca aagactgccg gccctaagac tgtcacttac 4500
accgaagttt gcaactcctg tgctgacaag cctatcactt acacctacat cgctccagag 4560
tacactcaag gtgccgaacg tacaacagtt acatcggttt gcaacgtttg tgctgagaca 4620
cctgtaacgc taacatacac tgcgccgaaa gccagtcgtc atacagttcc ttcacaatat 4680
tcaagtgccg gagagctcat ttcatccaag gggatcacga ttcctactgt tcctgcccgt 4740
ccaactggta cttatagtaa gtctgttgac actagccaac gtacactcgc taccattaca 4800
aaatcttcag atgagtctaa cactgttacc actactcaag ccacacaagt tttgagcggt 4860
gaatccagtg gaattcaagc tgcttcaaac agcacgagca tctcagctcc aactgtcact 4920
acagctggga acgagaactc tggatctaga ttttcgtttg ctggactatt cacagttctg 4980
cctcttatct tgttcgttat ataa 5004
<210> 35
<211> 1335
<212> DNA
<213> Pichia pastoris
<400> 35
atgcagtttg cttccttact gcttctcttg tatattttct tggggcaaat ttatcctact 60
gaagcagcaa aatattttgt tcgtctgaag aagcctcaca cactagacct cttgttcaaa 120
caggatgaag cagatgcatc tgctgagaac cgaatctctc ttcatggttt aagggaccga 180
atcaaaaaaa agatctcttt tggaacgttc gaaggttttg ttggtgaatt cacaacagaa 240
cttgtagaaa aactaaaaaa gaattcgttg attgcagaca taactcctga cattatcgtc 300
tcatcttgcg atatcgaatt gcagtccccc gctcctgatc acctggctag gttatccaaa 360
gaaggtgccg taagagcaca agatcgtctt cttggaccgg aatttttcta cgatggtgac 420
tggactggag aaggcgtcaa tgtatacgtg atagacacgg gtatcagggt aaatctagat 480
gaatttgagg gcagagcatc atttggtgct gattttacag gcactgggaa agatgactct 540
gttggtcatg gaacccacgt agctggtctt attggctcca aaacttttgg agtggccaaa 600
aatatcaact tgatatccgt aaaagctctc tctggtaatg ggagcggttc gctttcagag 660
gtcctacagg cgattgaatt cgcagtcaag catatgaaag ccagtcgtaa gccaggtgtt 720
gctaacttgt ctctaggtgc accaaaaaat tcaatccttg aaaaagcgat tgaagaggca 780
ttcaagaacg gtttagtcat agtagcagca gctggcaatg ccttcgtgga tgcctgtaac 840
acatcccctg caaactctcc atatgcaatc accgttggag ctataggtga tcacaacgat 900
gaaataacta gattttccaa ctggggagcc tgtgtcgatc tttttgcagg aggggacaca 960
attgtaagtg taggacttct caatggagtc gctgtccgca tgtctggaac ttcgatgtct 1020
gctccaatag tcgcaggctt agccggaata ttacttgacc agggtgtggc cccagaagat 1080
gtaaaaggta agttaataga gctctcagat gaagggaaga tcaacgataa tactggaatt 1140
ctaaagccgg gaactccaaa ccgaatagcc aacaatggaa ttcgaaaaag tgattatgaa 1200
gatcaaaaag aaaatgacaa tgatgaagac gatgaagacg gggaagacaa tctagaagac 1260
attgaagagg acgaggatta ttgggatgaa gagagaaggt atagggaata tgcggtatct 1320
agtttagtct tctaa 1335
<210> 36
<211> 546
<212> DNA
<213> Pichia pastoris
<400> 36
atgttcaaca ttatccaacg gatacagagt ttgagcaatt tttatttaac ggtttccatt 60
ctattatgta ttgttacaac agttgtctca attattagta tgttcttgga tgaaacgtcc 120
agtattcctg cccaattaag caatgttgta atatcaacaa atttaaagta tagcagatcg 180
tttggttcag tcggtggtag acctaaagaa aactccaaga ttttatttga tcttgatatg 240
gatctggctc cattattcaa ttggaatact aaacaactgt ttgtacaatt ggtagcagag 300
taccctacct ctgttgccga tgatggtgcg aaggtgacct attgggatag cataattact 360
gagaaaaagt acgcaagagt gcatgtcaat aagcagaggg gaaaatactc agtttgggac 420
gtgtcggact cctttcaagg ccgcaatgct acggttaaac tgaaatggaa cttacagccc 480
tatgtcggct ttctattctt tggacaaact aagggagaga ttgaggtggc ctatcctgca 540
acataa 546
<210> 37
<211> 870
<212> DNA
<213> Pichia pastoris
<400> 37
atgagtgtca tagtgcatcc tcttgcacta ttgacaataa tcgacgagtt ccagagacga 60
ggtcgcaaca acgattccat aatattcggt gggttacttg gtaaacatga tgaatccacc 120
aaccaaatat ctgttgttaa cagctttgtg ataccattga tcgataatca gtttttgaat 180
aaagagtact tgcaggacat gctactcaaa ttttctatca ttaattccaa ctttcgattc 240
gtaggttact atcacgttca atctttaaac ggtaccgaaa ctcaacagta tgacttgaac 300
gctattaacc tagtatgcca agatgataat aggccttcgt cctttgtcca ttggatagta 360
acagatccaa aagagttcaa atcattctcg atgtattact tggatgattc aatggttcaa 420
ctcgtcaatt ccaatattca acattacatt tctaaaccat tgccctatga atttaaaaac 480
cttctgtctg agaaaattgc tatcgacaca atcctcaagc aatccaggct agaaaaagac 540
ttatccacca aaaactcact gaagaaatta aacaatagtt atatcgacat tcattcctca 600
ctgaacgttc tctataaatc agtcaatagg cttattcgtt acctcaaaaa atgctcaaaa 660
tcagaagttt caattgacta tgacacagtt caggaaatga atactgtaat actgaaaatt 720
gaaaggctta aattgatacc ccaagtcaag gaggagtttg acttagtgac tctttcacta 780
ctggtagaca atcttgatca gatggatcat cttttgtatc tccggaaaca agtggaacag 840
tacaaaatat ctgaatcaat gtatagttag 870
<210> 38
<211> 1167
<212> DNA
<213> Pichia pastoris
<400> 38
atgaaatttc actcgattgt cttcacattt tcactcgttt tgagttcact ggcgttgtcg 60
ataccatggg tgtctgacca catggtccag catctttttg ccgacccttc aatcagtaaa 120
ggtcctgatg tagatctcgt tgggctacat aagcatttgg tcagcatcaa atctctttcg 180
ggctatgaac aagaagtagt atcgtggttg gccgattatc tagccagtag gggtcttact 240
gtggagttga acaaggtcga ggacgaaact gaacgttaca atttgtatgc ttatttggga 300
accacccgca acactaaggt tgtgctaact tctcacttag acacagttcc cccttatctt 360
ccctacaaag ttgaggaagg tggctatatc tttggcagag gaagctgtga tgctaaggga 420
tcagttgcgg cacaagtgat tgccttccta aatctcttgg aagagggctc catcaaagaa 480
ggtgatgtca gtcttttgta cgtcgttggt gaagagattg gaggtgatgg aatgcgcaca 540
gctagcaaga ccttgggtgc taaatgggac actgccattt ttggagaacc taccgagaac 600
aagcttgcca ttggacacaa gggaattgca ctgtttgacc tgaagattac aggaaaatcc 660
tgtcattctg gataccctga gctgggaatt gatgccgacg ctatgttggt ccagattttg 720
cacaagttgc tttttgagac ttcttggcct gtcagtgatt tgctgggaaa ctccacagtc 780
aacgcgggac agatcaacgg aggagtagct gctaatgtta tttcttcgga agcacatgcc 840
aaggttttaa tccgcgtggc taaagacatt gacgctgtag agaagctgat ctacgaggcc 900
attgccccct tcgaggagta tacagacatt acctttcact ccaaagaaga tgctactttc 960
ttggattaca aggttgaagg gttcgagaac tacattgcag cctacagtac cgatgtacca 1020
ttcctagtga cgggctccaa tttgaccaga tatttgtacg gaccaggaag catcatggtg 1080
gctcatgggc ctgatgaaat ggtcaaggtt tcagacctgc aggatagtgt tgacggatac 1140
aagcgattag tctccgtctc actttag 1167
<210> 39
<211> 1776
<212> DNA
<213> Pichia pastoris
<400> 39
atgccagaga aaaagaaaca aaaaaaagag tcgacatctc cattcaaggg taacctagtt 60
gggatctcat tggtagctgt ggcattgttt gccatctacc agtacctcta cccaagctcg 120
ttttcctctc agcctgaaac cccagcccca gttttcgatc tgagcagtga attagaagca 180
ttgtgtcccg tgtaccctgc agtcagatct tccgacttcg aaaaggatcg ccccatctta 240
gagagaattc tgaacgatcc ctcatttaga atcgcttctg ctcaaaaact gagtaaggct 300
gttcagatcg atacccaagt gttcgacgaa caattggacg tggctcaaga ccctgaagtt 360
tggaccaaat tcgtcaagtt ccatgaatat ttggaggcaa ctttccccac cgtttactcc 420
caattgaagg tcgacaaaat caacacctat ggcttggttt tcacttggga aggctcagac 480
cctagtctga aaccactcat gttcttggct caccaagacg tggttccagt ccagaaagat 540
actcttcagg attggtcata tccccctttc gaaggacgta tcgccgatga cagagtttgg 600
ggacgtggat cagctgattg caagagttta ctgattgcat tactggaaac cgtagaattg 660
ctggtagatg aagggtactc accaaagaga ggtgtcatcc tcgcatttgg attcgacgaa 720
gaagcttcag gtacctacgg tgctcacaat atctccaagt ttttgcttga gaaatatggg 780
ccagatagta ttgccctcat tttggatgaa ggtgaggctg tcagttacgt ggacaagaaa 840
caaactaccc tcgttgcaaa gattgctacg caggaaaagg gttaccttga cctagaggtc 900
gcattgacca ctgtaggagg ccattcttct gtccccccta agcacactgc aattggcctt 960
atttccaagt tggtcacaca tatcgaagat catccattgg acccagaaat tagtaccaga 1020
aatcctctgg tacagttttc gaactgtctt ggtgcagctg gggctttgag agatgacttc 1080
aagactgctc ttgttgcata cagcaaggat ccgtcgaaca acattgtcaa acaaggtgtg 1140
attaaaggta tttccaagat tgcatttttc ttcggttctt tgattaccac aacacaagcc 1200
accgatctta ttttcggtgg agagaagatc aatgctttgc ctgaaagtgc tagagtagtt 1260
atcaaccata gagtggacgt tgagcgtgat tcagcccaaa tcatagacag attgattcac 1320
ttccacgttg ttcctattgc caaggagcac ggtttcaagg tcacttacag tgactatggt 1380
agtgacaaag ttgaaactgt ctacgagcca gaaggagttg cctcattggg agaattccac 1440
gtttctcctt tctccagagt ctgggagcct gctccagaat ctccatccga cgacaatgtc 1500
tggtccatca tttctggtac cactcgtacg atatttgagg agtttgtgga cccctcggct 1560
aaacttattg caagtccata catgatgcct ggtaacaccg acactcgaca ctactggccg 1620
ctgacaaaga atatctatag atacgttcca ggtattgtag atatttacaa ggctaagata 1680
cactcggtag atgaatctac cgaggttgat gcccacttgc aagttatagc tttctaccac 1740
gagttcatca aggttgccag cgaatgggag ctttga 1776
<210> 40
<211> 1275
<212> DNA
<213> Pichia pastoris
<400> 40
atgaaatcct ctaaagaact atacaaggag gctctcaact atgaatactc ttccgcggtt 60
tctttcaagg cctgggttcg aagtgctcaa atcattttgc gacatgcccg gcagtttgct 120
gaacaaagat acatcagtga gtgctataag ttgtctgttc gttttgtaga cttgattgtg 180
aacaagatgg ccacgcataa agagctcaag caattgaaga aaataaatgc accagtatat 240
ctcacctatt tggatttggc tacgaagaaa gtcccagatg tcatcaagga atgtgaggcc 300
ttgaagacaa ttttggatga tgagtaccaa agctacctca aactgcaaca attgaaacga 360
cagaagcaga aagaccaatt gatccatcat cagaatcagg ctcaaacgca taaattacgt 420
agatcttcat caatattgaa agatcatatc aacgctgttg atgaaagagc gctgttgaaa 480
caactacagc agttgacata ccatgatcgt gaattcgcaa ccgcaataac ggagatgcca 540
aattatccag agatccccca gctgagtatt tcaacgaatc agaacactag atcagaggca 600
cccccacttc caccaagagt atcgcaggaa cagtcattag caccagtatc actagattca 660
tcacaggcag atttacaaca caaaactgtt aacttcaccg aagctgggca accattacga 720
acagtattta tttcagatag actccaatct gagttcctta gactagcgga accaaacacg 780
atacaaaagc tagagacttg tggcatcctt tgtggaaagc tcgtcagaaa tgcattcttc 840
atcacccatt tggttatacc agatcaagag tcgacaccaa acacatgtaa tacaagaaat 900
gaggaaaagt tattcgacac tatagatcag cttgatttat ttgtccttgg atggatacat 960
acccacccaa cacaatcatg cttcctgtct tccatagact tacatacaca gaattcgtac 1020
cagatcatgt taagcgaagc aattgccatt gtgtgtgcac cagcacctca gttttctcat 1080
cattcttttg gatgttttcg gctaacccat cctccgggaa ttccaaccat tacacaatgc 1140
actaggacgg gatttcatcc tcatgaggaa cccaatctgt atgtgacttg taatcgaaag 1200
aacatgggcg acgtgcaagg cggacacgtt gtgatcaaga atcatttacc gtttgaaaag 1260
cttgatctaa gataa 1275
<210> 41
<211> 1347
<212> DNA
<213> Pichia pastoris
<400> 41
atgactagtt ctgtagataa agtgagtcag aaggtcgctg acgtaaaact gggctcctcc 60
aagtcaacaa agaataacaa gagcaaaggt aaaggaaaat ccaacaagaa tcaagtggtt 120
gaggatgatg atgaggatga ttttgaaaag gccttggagc ttgcaatgca attagatgca 180
caaaaactag ctcagaaaaa agctgatgat gtgcctcttg ttgaagaaga agagaaaaaa 240
gttgaggaaa agattgaaca gcaatatgac cccatttcca ctttttaccc tgatggaaac 300
tatccccaag gagaagttgt ggattacaaa gatgacaact tgtaccgtac tactgatgaa 360
gaaaagcgag ctttggatcg agagaagaat aacaagtgga atgaatttcg taaaggtgct 420
gaaattcata ggagagttcg aaaactggca aaggatgaga tcaaaccggg aatgtcaatg 480
atcgagatcg ccgaactaat cgaaaacgca gttcgtggat atagtggtga agacggactc 540
aagggtggta tgggatttcc ttgtggtctt tctttgaacc attgtgctgc gcactattct 600
cctaatgcta acgacaaact tgtcttaaat tatgaagacg tcatgaaagt agattttggt 660
gtccatgtga acggtcacat tatcgatagt gcattcacgt taacattcga tgacaaatat 720
gatgatctgt tgaaagctgt caaggatgct accaatactg gtattcgtga agcaggtatt 780
gatgtgagat tgaccgacat tggtgaagcc atccaagaag taatggagtc ctacgaagtt 840
actttagacg gagaaacata ccaagttaaa cctatcaaga atctttgtgg ccataacatc 900
ggccagtata gaattcatgg tggtaagtct gttcccatag tgaagaattt tgacaacacc 960
aagatggagg aaggtgaaac ctttgcaatt gaaacctttg gcagtacagg aaggggtcat 1020
gtgataggac aaggtgaatg ctctcactac gccaagaatc cagatgcccc cgccaatgct 1080
atctccagca ttcgtgtgaa ccgtgctaaa caattgctaa agactatcga tgagaacttt 1140
ggtactcttc cattctgtcg tcgctacata gatcgtcttg gagaagaaaa gtacttattg 1200
gcattgaacc agttggttaa atctggagtt gttagcgatt atccaccctt ggtagatgtc 1260
aaggggtcat acactgccca atacgagcac accatccttt tgagacctaa tgttaaggaa 1320
gttgtatccc gcggtgaaga ctactag 1347
<210> 42
<211> 1119
<212> DNA
<213> Pichia pastoris
<400> 42
atgattcaca gctgtgctag tgctgagtgc tcaaaagcga ctgaatctac cttaaaatgt 60
cccttgtgtc taaaacaagg tcagatccaa tatttttgta accaaaaatg tttcaagaat 120
ggatggaaga tccacaaagc ggttcacgcc aaagatggtg atatagatgg ttcgtacaac 180
ccctttccca actttgccta caccggtgag ctcagaccag catatccctt gtctgtgaga 240
cgagaggttc cagagaacat tactctccca gattatgctc ttgatggagt accagtctca 300
gaaatcaaaa ataacagaat gaacaagatc aatttggtaa cggagccaga agacctggcc 360
aagctaaaaa atgtttgccg tttagcacga gaggttctag atgctgcggc tgcatctatc 420
aaaccaggag ttaccactga tgagatagat gaaatcgttc atagtgaaac aatcaagaga 480
gaagcatacc cctccccttt aaattacttc aattttccca aatctgtttg cacatccgtt 540
aatgaagtca tctgccacgg tatacctgat cgtagaccgc tccaggatgg tgacatcgtg 600
aacctggatg ttacccttta taaagatgga tttcatgcag atctgaatga aacgtactat 660
gttggagaga aggccaagac taacaaagat ctggtcaacc tcgtcgagac aaccagagaa 720
gctcttgctg aagctatccg tttagtgaaa cccggcatgc cgttccgtca aattggtact 780
gttatcgaaa actatgtgac tgaaagaggc tgtgaaactg ttcgttctta cactggtcat 840
ggtatcaata ctttgttcca cactgaacca accattccgc attacgctcg taacaaagct 900
gttggagtag ccaaaccagg agtggtattc actatcgaac caatgttgac tctgggcact 960
catcgtgacg tggtttggcc cgacaactgg accgccgtta ccgctgatgg aggaccaagt 1020
gcccaatttg aacataccct tttggttacg gaagatggtg tggagattct cactggcaga 1080
acggaaactt cgccaggcgg tgccatctca agactataa 1119
<210> 43
<211> 1605
<212> DNA
<213> Pichia pastoris
<400> 43
atgctctata agaccacctt gtcaatagca cacacgagtg tgatattgtt gtcattgata 60
accgccataa gttgctttga gttgcatctt cctcagaagg tttctcatat agtagacagt 120
ttacaatata cttgcggcca atttttgcaa aagcagcaga tctttgcact ctataacaag 180
caaaatttca ccgaaatagt gaaccagaat atcaagggaa tagaggagag agttttgtct 240
gagttgcttg aagaaagatt agagaatgaa tcccagaatg attattatac cgccaattct 300
caaaattggc ctatcgactt ggatcagtac tcagaatcat ttgtaataag gatcacatct 360
gaagatgagt ttatcaagta cttgatcttc aaggaagcta aagctttgca tatttccata 420
tgggagcaat ctgttggttt gatagatttg aaggttgacc gtgatcagat gcaccgccta 480
ctttacaacg tggagtcacg catactggaa cgaagaacga gaagtgttga cagtccagtt 540
tctgaatata aagtacaatt gatgattgga gatcttccac agcgaatcta cgaaacatat 600
ccttcgacaa aagtgacatc tttgcaagcc ctaggagagt tcccttcttt ccagaaccta 660
agtaatgctt tttttgagga ttttagaacg ctggaaacta tatacgactg gttcgaagaa 720
atacagaagg aatttcctaa gctagtgtcg atcaactgga ttgggcaaac ttatgaaggt 780
cgtgatctga aggctcttca cgttagaggg aagcactctg gcaacaaaac agtagtcgtt 840
acaggtggaa tgcatgcgcg tgaatggata tcagtaacca gtgcatgcta tgccgttcac 900
aaactgctcc aaaactatgc tgacggacac cacaaggaag cgaaatacct ggacaagttg 960
gactttttgt ttgttccagt tttgaatcct gatggatacg aatatagctt taacgaagac 1020
aggttgtgga ggaagaacag acaagaaact tatatgcccc gatgttttgg tatagacatt 1080
gaccattcat ttgattatca tttcgtgaaa tcagaagact taccctgtgg agaggaatat 1140
tcgggtgagt cccctttcga aagtatagaa agtgaagtgt ggaataattt cctgaacaga 1200
accaaagaag aacataagat ctacggctat atcgacttac actcgtattc gcaaacggtg 1260
ctgtatccct atgcgtactc atgcgaaatc ttaccaaggg acgaggaaaa cctgattgag 1320
ctaggttacg gtattgcaag ggccataaga aagagtacag ggaaaaaata tcaagtgttg 1380
aaggcatgcg aagacaggga tgcagatcta ttgcctgatt tgggaggagg aaccgcttta 1440
gattatatgt accacaaccg tgcatactgg gcgtttcaga tcaaattgag ggattccggt 1500
aatcatggct ttctccttcc caaaaagttt atatacccag ttggaacaga ggtttatgcc 1560
tcaattcagt acttttgttc ttttgtgctg aatttagaag gctaa 1605
<210> 44
<211> 1191
<212> DNA
<213> Pichia pastoris
<400> 44
atgaaattga ccataacatt agcccataac gatcaaatct tggacattga tgtgtccagt 60
gaaatgctac tatctgacct caaagtcctg ttggagttgg aaacttccgt acttaaaaac 120
gaccaacaat tattttacaa taacaacctg ctcactggag atgactcgcc actggaagat 180
ttaggactca aagataatga actcataatt ctgagcaaag tcgaagcaca tagtgatgtc 240
aattcacact tgaactctgt tagagaacag ttgatacaaa acccgctata ccaggccagt 300
ttacctccaa gtcttagaga taagctcgac gaccctcaag gcttcaaaga agaagtggaa 360
aaactaatcc aattggggca gtttggacaa tacgggcctt cccgtacttc cgtccaacag 420
gaattagaca gactacaaag agatcctgac aatccacaaa atcagaaacg aattatggag 480
ctcattaacg aacaagctat agaggaaaat atgaatactg cttttgaaat ctcacctgaa 540
tctttcgttt ccgtgaatat gctctatata aatgtggaaa ttaatggtgt ccattgtaaa 600
gcattcgtcg atagtggagc ccaaacgacc ataatgtccc ctaaactcgc agagaaatgc 660
aaccttgcga atctaattga taaaaggttc cgaggagtcg cacagggtgt aggaagttct 720
gaaatcattg gtcgtatcca ttctgctccc ataaaaatcg aagatattat tgttccctgc 780
tcattcactg ttttggatac caaggttgac cttctattcg gacttgatat gttgagaaga 840
catcagtgtg tgattgacct taagaacaac tgtttacaaa ttgcagacag aaagacagaa 900
tttttaggag aagcagacat cccaaaggaa ttctttaacc aaccaatgga agctccatcc 960
acagctcctg tcccaaaacc tgtacaacct cctcaacaac tcggtcagcg gccggctgga 1020
agccctccct ccacaattca aagaccagca gtacaaccgc cacctgtgga tatacctcca 1080
gaaaaaatcc agcagttgat caaccttgga ttcggagaag aggagtcgaa agaagcactt 1140
attagatcta gaggaaatgt ggaagttgca gcggctttgt tattcaacta g 1191
<210> 45
<211> 1553
<212> DNA
<213> Pichia pastoris
<400> 45
atgccaaacc ttccttctag cttgaacaag atgactgctc aagccgtgaa atacgcaaac 60
ggtatgtcat ctgccctctc ccgtgtttga gactctatcc actaacttta gattttatca 120
ccttcctgaa caattcacct actccatacc atgctgtcga ctccgtaaag tccaaattgg 180
tagagtcggg gtttaacgag ctcagtgaga gagttaattg ggccggaaaa gtcaagaaga 240
atggcgctta ctttgtgact cgtaacaatt cgtccattat agccttcact gttggcgggc 300
actggcagcc aggtaacgga gtgtcaattg ttggagccca tactgattcc ccaaccttga 360
gaatcaaacc catatcccat tcgactaagg agggatttaa ccaagttgga attgaaactt 420
atggtggagg cttgtggcat acgtggtttg acagagattt aggagtagct ggacgagtgt 480
ttattgaaga agaagaatct ggtaacattg tgtccaagtt agtcaagatc gataaaccag 540
tattgagaat ccccacacta gccatacacc ttaccaaaga gagagctaag tttgagttta 600
ataaggaaac tcaattccat ccaatctcat cgcttgaaaa ctcctctgaa aaggagaaaa 660
acaaagatga ggaacatgac gcttgtgcag gagaagattt gactacggag gagtttaagt 720
caattcaatc tgttgtggag agacacaaca aacaattgct tgatctggtg gctgcagatc 780
ttgattgctc tatatcccag atagtggact ttgaattgat tcttttcgac cacaacaaac 840
cagtactcgg aggtttgaat gaagaatttg tgttctcagg aagattggac aacctaactt 900
cttgtttctg tgccactgaa gcgcttataa atgccagtaa agataccaac aggttagatc 960
tggatactaa tattcaactg atctctctgt ttgaccacga agagattgga tcagtttctg 1020
ctcaaggagc tgattcttca tttctacctg acatacttca gcgtataaca agactaactg 1080
gtaatgaggt tagcaccgat ctggaaggac aaccaaattc tttcttttta gagtcaatgg 1140
ccaaatcttt cctactatct tcagatatgg cacatggtgt gcatcccaac tatggggaag 1200
tctatgagaa gctaaatagg ccaagaatca acgagggacc agtgatcaaa ataaacgcta 1260
atcaaaggta cagcaccaat tccccaggta ttgttttgct caagaagatt ggtgagttgg 1320
gaaaggtccc cttgcaattg tttgttgtta gaaacgactc tccctgtggg tcaacaattg 1380
gtccaatgtt gagtgctaaa cttggacttc gaacgctgga cctcgggaac ccccagctct 1440
ccatgcattc tatcagagaa actggaggtg ctcgtgacgt taaaaagttg gtcgatcttt 1500
tcgaaagcta ttttgagaat tattacacct tggagcctaa gattaaggta taa 1553
<210> 46
<211> 1413
<212> DNA
<213> Pichia pastoris
<400> 46
atgaacaaag gtccgaaaga attggagggc cgcaagtatc cagcaagagc ccatgcactg 60
acggtcaaaa atcactttat ccaaaagaag gctgacattt caagtcgttc tgcaatcttt 120
attagtggcg aagatctcaa gttgtatcct tactgtgacc aaacagctcc tctcagacag 180
aatcgttatt tcttttatct gtcaggttgt aatatccctg gatcccatgt cctttttgac 240
ttggacgccg aattgttaat tctggtgcta ccagaaattg attgggatga tgtcatgtgg 300
agtgggatgc ctctttcgat tgaagatgcc tacaagacgt ttgatgtgga caaggtggta 360
tatcttaaag atttgcaagg ctttttgtcg tcgtttggaa aaatatatac aactgacatc 420
aatgatgaaa attctaagtt tggcaatcta ctaacagaga aagatcctga cttgttctgg 480
gctctggatg aatccagatt gatcaaagac gactatgaac tcactctaat gagacatgcg 540
tcaaaaattt ctgacaattc ccattacgct gtcatgtcgg ctcttccaat tgaaactgac 600
gaaggccata ttcacgctga gtttgtttat cattcgttaa gacagggatc taaatttcaa 660
agttatgacc cgatttgttg cagtggacca aactgtagta cccttcatta tgttaagaat 720
gacgattcta tggagaataa acacaccgtt ctaatcgatg ctggtgcaga atggaacaac 780
tatgctagtg acgttacaag atgttttccc atcaatggag attggacgaa agagcatctt 840
gagatctata atgctgtttt ggatatgcag gaccaagtta tgaagaagat taagcctgaa 900
gcccattggg atgagctaca ccttttggca catcgtgttc tcattaagca ttttttgagc 960
ctcggcatat ttcataacgg aacagaggat gagatatttg agagtggagt ctcagtatca 1020
ttctttcctc atgggctggg tcacctttta ggaatggata ctcatgatgt tggtgggcac 1080
cccaactatg atgatccaaa ccctctattg agatacctaa gattgagaag agtgttgaaa 1140
gaaaatatgg tagttacgaa cgaacctgga atctacttct ctccctatct tgttgaattg 1200
ggactgaagg atgataataa ggcaaaatat gtcaacaagg atgtactgga aaagtattgg 1260
tatgtcggag gtgtgagaat tgaagacgat attcttgtta cgaaagatgg gtatgaaaac 1320
ttcaccaaga ttactagcga ccccgaagaa atttccaaaa tcgttaaaaa ggggttggag 1380
aagggtaaag acgggttcca taatgttgta tga 1413
<210> 47
<211> 2612
<212> DNA
<213> Pichia pastoris
<400> 47
atgacatctc ggacagctga gaacccgttc gatatagagc ttcaagagaa tctaagtcca 60
cgttcttcca attcgtccat attggaaaac attaatgagt atgctagaag acatcgcaat 120
gattcgcttt cccaagaatg tgataatgaa gatgagaacg aaaatctcaa ttatactgat 180
aacttggcca agttttcaaa gtctggagta tcaagaaaga gctgtatgct aatatttggt 240
atttgctttg ttatctggct gtttctcttt gaccttgtat gcgagggaca atcgattttc 300
caatttgaac gagtacgttc cagattcaaa cagccacgga actgcttctg ccaccacgtc 360
taatcgttga accaaaacag actgaattac ctgaaagcaa agattctaac actgattatc 420
aaaaaggagc taaattgagc cttagcggct ggagatcagg tctgtacaat gtctatccaa 480
aactgatctc tcgtggtgaa gatgacatat actatgaaca cagttttcat cgtatagatg 540
aaaagaggat tacagactct caacacggtc gaactgtatt taactatgag aaaattgaag 600
taaatggaat cacgtataca gtgtcatttg tcaccatttc tccttacgat tctgccaaat 660
tcttagtcgc atgcgactat gaaaaacact ggagacattc tacgtttgca aaatatttca 720
tatatgataa ggaaagcgac caagaggata gctttgtacc tgtctacgat gacaaggcat 780
tgagcttcgt tgaatggtcg ccctcaggtg atcatgtagt attcgttttt gaaaacaatg 840
tatacctcaa acaactctca actttagagg ttaagcaggt aacttttgat ggtgatgaga 900
gtatttacaa tggtaagcct gactggatct atgaagagga agttttaagt agcgacagag 960
ccatatggtg gaatgacgat ggatcgtact ttacgttctt gagacttgat gacagcaatg 1020
tcccaacctt caacttgcag catttttttg aagaaacagg ctctgtgtcg aaatatccgg 1080
tcattgatcg attgaaatat ccaaaaccag gatttgacaa ccccctggtt tctttgttta 1140
gttacaacgt tgccaagcaa aagttagaaa agctaaatat tggagcagca gtttctttgg 1200
gagaagactt cgtgctttac agtttaaaat ggatagacaa ttcttttttc ttgtcgaagt 1260
tcacagaccg cacttcgaaa aaaatggaag ttactctagt ggacattgaa gccaattctg 1320
cttcggtggt gagaaaacat gatgcaactg agtataacgg ctggttcact ggagaatttt 1380
ctgtttatcc tgtcgttgga gataccattg gttacattga tgtaatctat tatgaggact 1440
acgatcactt ggcttattat ccagactgca catccgataa gtatattgtg cttacagatg 1500
gttcatggaa tgttgttgga cctggagttt tagaagtgct tgaagataga gtctacttta 1560
tcggcaccaa agaatcatca atggaacatc acttgtatta tacatcatta acgggaccca 1620
aggttaaggc tgttatggat atcaaagaac ctgggtactt tgatgtaaac attaagggaa 1680
aatatgcttt actatcttac agaggcccca aactcccata ccagaaattt attgatcttt 1740
ctgaccctag tacaacaagt cttgatgaca ttttatcgtc taatagagga attgtcgagg 1800
ttagtttagc aactcacagc gttcctgttt ctacctatac taatgtaaca cttgaggacg 1860
gcgtcacact gaacatgatt gaagtgttgc ctgccaattt taatcctagc aagaagtacc 1920
cactgttggt caacatttat ggtggaccgg gctcccagaa gttagatgtg cagttcaaca 1980
ttgggtttga gcatattatt tcttcgtcac tggatgcaat agtgctttac atagatccga 2040
gaggtactgg aggtaaaagc tgggctttta aatcttacgc tacagagaaa ataggctact 2100
gggaaccacg agacatcact gcagtagttt ccaagtggat ttcagatcac tcatttgtga 2160
atcctgacaa aactgcgata tgggggtggt cttacggtgg gttcactacg cttaagacat 2220
tggaatatga ttctggagag gttttcaaat atggtatggc tgttgctcca gtaactaatt 2280
ggcttttgta tgactccatc tacactgaaa gatacatgaa ccttccaaag gacaatgttg 2340
aaggctacag tgaacacagc gtcattaaga aggtttccaa ttttaagaat gtaaaccgat 2400
tcttggtttg tcacgggact actgatgata acgtgcattt tcagaacaca ctaaccttac 2460
tggaccagtt caatattaat ggtgttgtga attacgatct tcaggtgtat cccgacagtg 2520
aacatagcat tgcccatcac aacgcaaata aagtgatcta cgagaggtta ttcaagtggt 2580
tagagcgggc atttaacgat agatttttgt aa 2612
<210> 48
<211> 2127
<212> DNA
<213> Pichia pastoris
<400> 48
atgacctgcc aaagtgtaga agagctggat gctattgttg aatcaaagct tagggaggtt 60
gataataaag tttcgaacgg aaatgttgac ttcatcaaac aatatctgat tcaggcgatg 120
aactattatg acaagtatag atctgaaatc aaaaaaattg gacccacaga aaagaaccct 180
aaatactatt gttttcaaga ggcagcgtat gttaactaca aagcttccca agctttacta 240
agagagagaa tacccaagct gcctggcttt ggaggatata aatctgcgta ttcaaaaatc 300
tatcgtgaac tgatagaaat ggtagagggg caagaacatg agattgccca gataaaaagc 360
ggcttaagga aaaacttttg tgatgataca ttagttcttc gactgagaag tttaaaatca 420
ccatctgcta ctcagcccaa aagtttaccg gattctacac ccacttcaca atttaaacca 480
aaaccttcaa agccttttag tatcacaatc aatgaggaat acatttcggt tgaccaattg 540
tcacgccttc ttaaaacgaa cccgaatgac atactcctca ttgatctacg gtctcgtcaa 600
gagtacgacg tgtatcacat tgaagatggc tccggggtgg acatgtcaat atgtatagaa 660
ccaatgagta tcagaaacgg atacacagca gaggatcttt atcaactttc aatggccgtc 720
aatccagatt atgaaaggag attgttcaag aatcggtctc agtatgaact gttggtatgt 780
tatggtaatt atgacaacga ggctactgtt caaatgttca tgactatcat gaataaagat 840
acttccctca agaggcggag cgtctatttg aaatccggaa ttaagggctg gaatcaggat 900
ctgagttttc aagattcgaa accgaatggg tacttaacta gtacgactga ctacttcagt 960
aacactccga aacacacaat tacgcccaaa tcatcaaaat caagttcaaa acctacttta 1020
aaaactactg tcaactctgg gcctgcccac actgttggga tcaataatct aggaaataca 1080
tgttacatga attgcatact tcaatgccta ttagaaagtg ataagtttgt ttcatttttt 1140
ttacaaggcg attataagaa acatatcaat attaatagcc gattaggctc gagaggtata 1200
ttggctacag gatttcattt gttagtgcta ttaatatcca gatcatctgg taaaacagtg 1260
actccttctt catttgccaa agatgtttca acagtgaata agaattttaa gttaggagag 1320
caacaggatt gttttgaatt tttagatttt ctcctggata gtttacatga agacctgaat 1380
gaatgtggga atgaaccacc aatcgcagaa ctcacacctg aagaggaaaa gcttagggaa 1440
gctttaccta tcaggattgc ttcgaccatt gaatgggaaa ggtatttaaa aaacaatttt 1500
agcatagtag aagatgtgtt tcaagggcag tacttctcca gattggaatg tacagtctgt 1560
aaaagcactt caactactta taactcattc agttcactgt ccttgccaat cccattagat 1620
cgacaaaatg tcacactaga tgactgtttc caggcttttt gttctgtaga agaattgaac 1680
ggagatgaca gatggcattg tccaagctgt aaaaaaaagc aggtcgcttt taagaaactt 1740
ggtatctcta gactaccaag tgttctgatc gttcacttta aaaggtttca ggtcaagtgg 1800
gaaacaggtc atataatcaa gatagacaag tttatcagtt atccgttcaa gctatcaatg 1860
gacaaatatt ggcccaaagc tcaatcagaa gaagaactaa gaaacttgga gaagctacca 1920
tcgagaaatc agaatccccc tttcaattat cgattgacag gggtggctaa tcattttggg 1980
accagaacat catctggtca ctacacatca tatgttcaaa aaggtggcca atggtattac 2040
tttgacgata gtgctgtgac tagcaatgtt gatcgtcata aaatcgtaaa tgggaacgcc 2100
tatgttttat tttatcgacg tagttag 2127
<210> 49
<211> 669
<212> DNA
<213> Pichia pastoris
<400> 49
atggaagccg tgaatttaca aattgaatgg attagacagg tgcctccagt tactgtggct 60
cttgtagcat ccatgtcaat gacctatttt ttgcaacgca tagatgtatt atcctcaaat 120
atgttcgtgt ttgaaagaca tcgtgtgttt aatgagatgg cctattctcg tttgatacta 180
agtttcttct tcagcgccca ttcgtttgtt ggattctttt ggacattgta cacattattt 240
cagaattcac aggcactcga gctgacctat gaaaactcaa tcgattacct ctactcattg 300
gtgataatag caggtttgat cgtggcatgg gcctcatact tggggggtcc gttcatgctg 360
ggatgggttc tagctgacgt cttgagaacc atatggtgca aacagaatcc caacgaaaga 420
atgtctattt tggggctagt ttccttcaag gcaggatact ttccatttgt aatacttgcc 480
atttcatggc tagaaggaag ttcaagaaat cttctattaa tgctaattag ccaaactgtc 540
agtcaggctt atatttttgg acaccatatg atgcccgaac tacacgggat cgatctgttt 600
ctgcctatat ggaaattcca gtgtttcaga cgtcagagac aaccaccaat tcatcagcat 660
caagactaa 669
<210> 50
<211> 927
<212> DNA
<213> Pichia pastoris
<400> 50
atgtcaaagg tggtggtatt cctaaatgga ttattggcaa taacctttac gtttgaactt 60
ctctctgttt taagcgtgcc aatcaccaag catatccaac tttgttctta tcaaggatat 120
aagtttggcg tgtttggata ttgcaccgag aataatatct gcacaacgat aggaatcggt 180
tatcatcgaa attcaataga cgaattgaga ggcttttcat taccaagtaa tgcaagaagc 240
tctatatcaa gcttgttggt ggttcatttg attggctgtg tttgcacctt tattttatgg 300
gttctaagtc tcatgttgaa tatggataga tttcacagat cattatggtt cttattaacg 360
tgtctagtat ggacttgtgc tttctttttt tttacattat tctccttcct ggtagacgtg 420
ttactatttg tgccacacgt tgcgtttgga ggttggttga tgttggtaag tactgtattt 480
ttggcattta caggaaccat tttttgcatc atgcgaagaa ctgtcagctc aagaaaaact 540
catttgaaga actacaacgg gggaagtaca agtttgatgc ggctgcagac gtatatctcc 600
aatagctcta gaggaagctc tgtaaccaat gatgaatacg tctggtttca agaaactcca 660
ttacaagacc tctacccccc agacaatccc aattacgacg acatctacgg aacgactgaa 720
cacgaactaa cccgcttgga cacaatatct cttgaaaggc caagaatagg ccttatcaca 780
aacgaaaatg ccagcggcga tggtggggta gtttccccac cacagaatga cagtacactt 840
ctggaatctt cgggcagaat taggaatggg ccactgggag accgaagtga atttcccaac 900
ggatcaacaa gcgaactttc tgcataa 927
<210> 51
<211> 714
<212> DNA
<213> Pichia pastoris
<400> 51
atgaaataca gtgaccaatt aatagaagag tacaaagaat tatggttaac agcgacatct 60
aatgagctta ctagagaatg gtgccaggga actctccacc tgagcaaatt atacgtttac 120
ttgacacaag acttaaagta ttttggggat ggatttcgac ttttaggcaa aaccatttcg 180
ttatgtcgcc gtaggcaatc gcttgtgtca ttaggcaaac atgtggggat gctcagtaat 240
agtgagaaca cgtacttcgt ggattgtatt aacgatctta ctgaacagtt attaagagat 300
gggatgtaca atgctgaaga attagaagaa atcagtggtt taacgttacc tgccgtggaa 360
aggtaccttt tattcatgag atcgatggta gagtcttcta caataactta tgcagaaatg 420
attactgtga tgtttgtaat ggaacaagtc tatctggatt ggtcaaataa tggactgaga 480
agtaaacctg acaacttgca ttggtggttc aatgaatgga ttgatataca tagtggggag 540
aactttgaaa gctggtgcca gtttttaaag gatgaggtag accgctgtat acaggagttg 600
aaggatgcta atagagatga tctcgtggcg agggttgagg agatttttag agaaacatta 660
gaacttgaag tcgaattctt taaaagttgt tacgatatca cggacgatga atga 714
<210> 52
<211> 357
<212> DNA
<213> Pichia pastoris
<400> 52
atgcactcga aatttaggtg ggtatgtgtc gatactcaat tctgcacaca ccaccaaaat 60
ctgtcgcctt tctcttatat ctccaacccg agtccaatgt cattttctta ccttgaaggc 120
aacatcgatt ttaaaggaca ggaacttgca aacaggatca ctaaaaaact aatcacattt 180
ggtgcaatta ttagttttct ggtaggattt ttgagtgaca acatcttata cactgtatac 240
actttcgcag cttttggttt attgactgct tctttggtta ttcccccttt tagcttctac 300
aaaaagaacc ctgtaacatg gttaccaaag aaatccaaaa tagagattca gcattga 357
<210> 53
<211> 3423
<212> DNA
<213> Pichia pastoris
<400> 53
atgacagact ctgttaactc tgatgattct gatctggaaa tcatagaggt gactgagcct 60
actccaaaag tggacctttt ggcccccaat ccagcattta attttactgc ccccataagc 120
aacagtaacg gcacaactcc aataaggaga aaacttgatg accaatccaa ctccaattct 180
tttgccagac tggaatcgtt acgggaatca tcagtgaaac cacaagctag tacgttcaat 240
agtagtaggt tcatccccca agccgaccaa ttttccaata atcagaataa tgaacttgat 300
aacaacaatg gattcgccga ctggatttct aagtcccaac ctgaatttcc ctttccactt 360
aatgatggac caaaaaagtc cagcaatcaa cctacaaact caaattttga agagatcatc 420
gatttaactg aagatatcga gataaataca tctgtccccg catctacatc atcttctacc 480
ccagttccct ccagcacaca gaatcagagc catcatatag ccaacaacaa cacagcacaa 540
gatgcgcata tcttccaagg gaaacgacct ctccaatcat attcagatga tgaagacgaa 600
gatttgcaaa ttgtaggatc caatattgtt cagcagcctc taggaattat gccaggaact 660
ttcaacgccc ctgcaaacat actccatttt gacggttcaa accagaatga acaagccaga 720
tggctggact tgcggataaa agatttgtta gataatcttc acaatcttcg agttcatgct 780
cagtcgaata ttatggagat caataggttc atttccactt tggggcattt aaacagagaa 840
gtttcagagc tcaatctaag atatcaatct atcgtgaaca atcctcaggc gaccgctaat 900
aatcaaggat acctcactca gcttttgaac aggattcagg agcttactaa tgaaaaagcg 960
cacatattta gagagatgga tacatccaag ataaaacagc aggagattca cagaagaatc 1020
catgctctct cgtcaacaat tgacaaactg aaaaaagatc gtgaacttat ctttcgaaat 1080
gctcaaaatg cttttcacgg tgatatgaag aatgaagttt tggaaggcca gtctttcatg 1140
gatgcaattc atagggcaaa tagcttgggt tatgcttcaa atatttattc tcgttctgat 1200
gaagacgctg gaagcttaca acggcttctt gaaaatatcc agcccgatat ggaggacaaa 1260
gacgatgatg aattggctaa aactccgaag gagttcaata ttcaactgct gaagcatcag 1320
agagttgggt tagattggct acttcggatg gagaagtcaa ccaacaaagg aggcatttta 1380
gcagatgcca tgggcctggg aaaaaccatc caggctatta gtattattta cgcaaacaaa 1440
tggaaaacac aagaagaagc cgaagaggag gcaaaacttg aagagaaggt tagatccgaa 1500
aagtctacat cagaaacgaa tggagaggtc agcaaaacgt caacggcaaa gtcggaaaag 1560
aaacccatcc aaggagacga aggatatttc aaaactacgt taataatagc accagtttct 1620
cttctacatc agtgggagtc tgaaatcttg ttaaagacga aaccagaata caggctaaaa 1680
gttttcattt atcacaagca aaaaatgtcc tcgtttgaag agctccaaca gtatgatata 1740
gtattaacat cgtatggaac tctgtcttct caaatgaaga agcattttga agaggcaatt 1800
aaggaggcag acctacagcc caactcttca tccataccag cagaagactc tggaggcata 1860
tctttcaagt caccattttt tgcaaaagaa acaaagtttc ttcgagtcat tctagacgaa 1920
gcccataaga tcaaaggaaa aaatacaatc acttcgaagg cagtcgcttt ggtgaagtct 1980
aaatacagat ggtgtttaac gggcacaccg ctacaaaata aaattgaaga actatggcct 2040
ctacttcgat tcttgagaat taagccatat tatgatgaaa agcgatttag aactggcata 2100
gtattaccta taaagagttc catgtcaggc aaatatgatt ccacagacaa gaagattgct 2160
atgaggaaac ttcatgccct acttaaagca atcttgttga aacgaaacaa agattcgaag 2220
attgatggag agcccattct caagttaccc aagaagcata tcattgacac attcatagaa 2280
atggaagcaa aagagttaga cttttacaag gatctggaag gacagacagc caaaaaagcc 2340
gaaaagatgc taaacgctgg aaagggacaa ggaaatcatt attctggtat tcttatcttg 2400
ctattgagac tgagacaaac ttgttgccac catttcctcg tgaagttatc tgagatgaag 2460
caagaagcca aattgaaaca ggaagttgct accaagatgc cacaattggc cacacaacta 2520
tctcctgctg tggtaaggag aattaacatt gaagcagagg ccggatttac gtgtcctata 2580
tgtttggata acatcataaa tgagaatgct tgtatattat acaaatgtgg acatgttgtt 2640
tgtcaagatt gcaaagacga tttcttcacc aattatcaag agaatgaaac tgatgacggt 2700
cttagagtgt ccaaatgtgt gacctgtcgt ttgcctgtca acgaaagcaa tgtaatcagt 2760
ttcccagtct acgacaagat tgtgaaccag catatttcag tgatggatat agttaaaagt 2820
gagtctccag tgttgtcaaa aattgaaatg attcaacaac tgatccggga gaacaaaggc 2880
gtcttcgaat cgtctgccaa gatcgataaa gcagtggaaa tgatacaaga gttactgaga 2940
gacaatccag gggagaagat catagttttt agtcaattca caactctctt cgatgtcata 3000
gaggtaatac tcaaagagaa caacattaaa ttcattagat atgacgggtc aatgtctctt 3060
agcaatagag atgctgccat tcaagagttt tatgagagta cggagaaaaa cgtaatgctt 3120
ctttctttga aagcagggaa cgtggggttg acattgactt gcgcctcccg tgtcataata 3180
atggacccat tttggaaccc atatgtggaa gaccaggcca tggatagagc ccatagaatt 3240
ggccagttaa gagaagtttt cgtctatcga atgttgatca agaacaccgt cgaagataga 3300
attttgacca ttcaaaatac gaaaagagaa atagttgaaa acgctctgga taaccagagt 3360
ttgaatacga tatccaagct tggcaggaac gagttggctt tcttatttgg tatcggcaat 3420
tga 3423
<210> 54
<211> 1080
<212> DNA
<213> Pichia pastoris
<400> 54
atggagtgta aaaaagtcaa agatcgccta gtcacggaat acttaaagat tgaatgtagt 60
cgacttaacc gaaggatacg ctccctgaaa aatccaaaag ttgagcaagc cctactgcaa 120
ttcaagaact cacgtttggc tcacatgaga aaggctcatc tggatggaat aagaaaccca 180
cagtatacgg atgacgccat ctttcaggca ttggaaacca tggatttgga ccacatattt 240
gagaaggcag gtagtcttta caactcacag caacaagatg aatcaaaaaa agattccctg 300
gatgaaacag atttcaccgt ggtggcgttg ctagattggt tcaagaatga cttcttcaaa 360
tgggtaaaca agccaccttg tcctgtttgc catagtgaag atgaaagccg cataagaatg 420
gtcggatctg caaggcccac tagtgaagaa ttgtcgtacg gagcaggggt cgtagaggtg 480
tttaattgtg accattgtag ctgtgcaatc agatttccaa gatataacga ccctaagaag 540
ctcctgagaa ctagagctgg acgatgtggg gaatggaata actgttttct gttgtgtcta 600
aaagccttgg gtctgaaagc tagatgtgtg aggaatgtgg aagatcatgt atggagtgaa 660
tactactcgg aacatctcaa gcggtgggtc catctggata gttgcgagaa tgcctttgat 720
caaccagaac tatactgcaa aggttggggg aaaaagatga gctattgttt tgcttttgat 780
gacactctca tagaagatgt gagtgccaag tacattactc aaggtagact gcctaaaatg 840
ctagacgacg aaaccatcag aatatgcttg tattttttca accaggaagc tcttaagatg 900
gtgagtgaaa atccagaggc attctactcc gctttggtta agtatcacag atgtctgtct 960
gcgaatagaa aagagagcgg gtcaaaatca cgagccgtga atgctagttt gacttcattg 1020
ttaccacgac aatctggtag cgcatcctgg acgtctgaga gaggcgaaaa cggactttag 1080
<210> 55
<211> 819
<212> DNA
<213> Pichia pastoris
<400> 55
atgcctataa aggggcggtt caccaaaaag aagccaaaaa ggaaagatga gccaaatcga 60
ccgtccccca cccagttcat caaaaaaata gcctcattga aaaagcagac caggagagat 120
gaggccctgg atgtgctaca cgaactagca gttgttgtgt cacctttgat gaaagagaac 180
ggtttcactg ttggattatt atgcgaaatg ttcccgaaga atgcctcttt attggggctg 240
aatgtgaata tgggttcaaa gatcatgatc cgattgagac ctagccacaa catgaacttg 300
tttttgccaa aaagagagat catcggtaca atgctccatg agttaaccca taatcgcttt 360
tcggcccatg atgtaaggtt ttatgacttt cttgagggtc tcaagagcag gttttttgag 420
attcaggtga aaggatcttt acaaactaca gggtatgtta actttagtga agttctatct 480
ggtaatgcgg cgagagggca actgattcaa aaggaaaaag agaaaggaca aagattgggt 540
ggtaataagc atgcaaaacc tatgagagtc ctaatcttgg aggcggccga gaagagaatg 600
atagactcta aatggtgcgg aggagctagc aatgaagtag gccttccaaa aattgaagat 660
ctaatggacg atgaagaagc tcaacactct gaactaaagg aagagaatac aaagaaggtc 720
agaaaaattg ttcaacctag caaaaagaaa attgtagatt tggaaaacct accgaatggc 780
aagtccatta ttattgatct aactaatgac gatgactaa 819
<210> 56
<211> 1719
<212> DNA
<213> Pichia pastoris
<400> 56
atggaacaca attgtctgaa agtcaatgaa ttggcgctcc agttggctca atcactgcag 60
aacagcaaag tcagcacagc tgatcctcta aagaagagga caagcagcta cagaggcctg 120
agtagcgagc ctataatcac agaggaagaa ccaacaatca agggcgacta taatagattt 180
tacagtcagt cttcagataa gcaagtattg gacaataaac catggttgca ggatggaaac 240
tatttcaaga ctgtatacat ttcaacgata gcactactga agatgatgtc tcatgcccgg 300
tccggtggtt caattgagat tatgggcatg ctgacaggta aggtgtttgc caacacatta 360
gtcgtaatgg attgctactt acttccggtt gaaggtacag agacacgagt gaatgctcaa 420
gcggaaggat atgagttcat ggtctcttat ttggataact taaaggaaat caagcataac 480
gagaatatca taggatggta tcactctcat cctggttatg ggtgctggtt gagtggaatt 540
gatgttgcca ctcagaattt aaaccaaaag tttcaagatc cctacctggc gatagtgatt 600
gatcctgaaa gatcagtcag acaaggattt gttgagattg gagcattcag aacgtttgct 660
gagccagccg ttggaagatc gtcgtcgtca gtttcctctg caagtggtgc aggaattagt 720
gatgttgcgt tttcttccgg tagaaacagt gcatctggaa tgtcctcagt tctgagtgca 780
agtaatatta gcattgccga agagctaagc aaacaatcga tcacccaaaa tgtttttgac 840
agaactacta caaagattcc caagggcaaa atgactgatt ttggagctca ttcaggaaaa 900
tattactcgc tagaggttaa ggttttcaga tctccactgg aggagaaact actggatacg 960
tttggttcta aaacctggat taaaggttta acgaactact ccaacgttgt taatgccgag 1020
gaaactcaag tggagttaat gcataaaata atggaagcca cggagaactt acggaaggaa 1080
tctccttcta aattgccatc tttggtgatg gggaacctga tttattcagg tgcctctcaa 1140
ggaacaacag ggaaccgcaa gcgctcaatg tccaaatctt ctatttattc gggtttacaa 1200
gcttcatcgg gtatacccag ttctaggtat cctacgaagg gaaaaaatat gagtggatct 1260
caattcaatg atgacccgct agcaagatca ctggataaaa taccgccaga tagtccagat 1320
caacagtacg atggcgcatt atccattcaa caaccgaaaa gagcatataa tacacatact 1380
tctagagcag gtgggttggc cagcgttctg tcctctggga gtatggatcc tcaaagttac 1440
tccatggtag gacgaatgag tctaactaat caatcgccgg ggacagctct gagaggccta 1500
aatacacctc ccaacaaacg accgcagaga aaccctggtc atacaagctc aggtcaagga 1560
ggaacgcctg gaggagtcag tcggtccaaa gagaaaatta acaagccaat aggtataagc 1620
atgattagca aggatttcaa ggttgtcatc tcacaacagg tcaaccagat gctacgtcgt 1680
cacgtccaga atgacctttt tggatccaat agtccctaa 1719
<210> 57
<211> 2181
<212> DNA
<213> Pichia pastoris
<400> 57
atggatcatg cccaacgatt gctagaacta agtttttaca atcaaagtct gggcaaatca 60
gtgatagcaa agaaatacag aatagaatcc tctcgatatt tgaatgaaca actggacaag 120
tccttgacaa gagataatga tctgattgga ttatgccgta tagcattaga caacaagttg 180
accatatcag ataagattat atggatgagc tctcaagttg aagacaactt ctttccgcca 240
gtttttcaag gcttgaagac gtatattgat agcgacgaga tttatcaaga gaaactttta 300
agcgtaccag cggattttga accaatagtt gaatggaaga gttgcacaga gttgcccaat 360
gaatggtcaa acaatggtgt ggacaattta tttcaggatt ctttagatga ctgttcgttt 420
gtagcttcat ttctatcctg caacaatatt ggtatccctc tcatggataa agtcattccc 480
cacaaaaact cgttcaaata tgcggttaga ctgactttca atggttgcga aaggttggtg 540
tttattgata gccgtttgcc tttgcttagg aatacttcca agactttacg agtgtcaagt 600
ttttctaaca aagatctctt atggcctagc atcatcgaaa aagctttcct gaaaatgtgt 660
gatgatgggt acaagttttc aggatcaaat tcagccattg caaactatgc tttgactggc 720
tggatccctg aagtcattaa aacttcttca tgtacaatag cagatattag ccgattgcat 780
gaggattttc ggaacggaaa cgtagtacta tgcttgggaa cgggcaatct gaccgagcga 840
gaatgcaaac agtatggatt gatccccaat catgactatg ctgtcactaa actatcattt 900
acgaatgatt cagaatacaa gtttgacatt cgtaatccgt ggactaaagg gcagaaagca 960
gtgacaatta cagatctttc aacctttgaa gttatctacg caaacagaaa tcctataatg 1020
ttttcgcaca tgaaccagct aagcggtatc tgtcaaagtc aggttaatga agagttcata 1080
gatctaattc ttaaccattc gcagtatacc ctaggcaatg acggtaattc tacaattgat 1140
gtgattcttt tctttgaaag acattcgtta agaaagaaaa tcagtgcaga gtctcgtatt 1200
gagattttcc aatcagaagg cgaaagacta atctccagaa gaaataaagc aagcaaggaa 1260
tgtgtttcta ataataccaa ctttcatttc ataacaatcg aactgaaacc gttagaaaag 1320
gtaactgtgg taatagatat cggcgagtct tcgattcgaa gccatccatt tactctaaag 1380
gcttttgcca atgattcaac tataactttg aacaaagcac tttctagacc tggttgtttc 1440
aagcaaatgg acctagagct aacgccctta aactctggtg ggaattggga taattatgct 1500
tattacaaaa atccacaact catagtcact cttcacggag attcaacgga tgaagctcca 1560
tttgaatctg ctgttttcag caaaagtgat aagaccctat ttacgtatac agtgttttgg 1620
aaaagtgacg atccagactt tcctttcatc actgacgcaa gcaagaacaa gctcgtaagc 1680
acagacaata agtataaata cagatcatgt acaagatcaa gagttgtttc ttgcgacaaa 1740
agctatttgt tcgtgctgag ctcctacgaa cctgatgcaa ttgagtcttt caaagtattt 1800
tttcaatgtt cccacgattt ttctatagag tgggctgaga cgtcgcttgg gcttttcaca 1860
aaggaagaaa ctttctcctg gaaggaccaa ttagtcaagg agttcattat tcaagtctat 1920
aacccttcaa agttgaaagt tcacgcagta aacaccaaca acaaacgcag atcaaaacta 1980
aattgctctc tctcattcca aaacacatta atcagctctt tgcaagacta cacagacaat 2040
ctctatggat gctttattag cgggaacttg gagattcccg gcaagtatct attacaagtt 2100
cataaaaaca ttatatctaa cgaagaatgt ttggtcgaaa ttggatctag ttcgtcattt 2160
gagttatggg aacatcatta a 2181
<210> 58
<211> 1137
<212> DNA
<213> Pichia pastoris
<400> 58
atgttgaaaa ctcgatttca ttccagaaag ggttttgtaa tctacagtgg agatgatgaa 60
gagagtgacg aagagagtaa acaatggatg tttcccgagt cgacctttgt aaccaatggg 120
tttgaccaat tgttcaaggt gagaaatgtc aataccatta atgacgacga tgacggctac 180
caatcgttcg atcaaccgga ttgggcgcaa gatttaaccg cagatactca gtatcttgct 240
ttaggtgacg aaggggagaa tcatcgttca caacaagaga taggcaacag gaaaagagcc 300
aacaaaaagc aaaagaagcc aactaaagca aagacaaaac gtcaacaaag acgcacagcc 360
aaaaatgatc aatccacgga acgatctgcc atttcacaac cttctaactt aagtacactg 420
aactccttac tcaaatctgt tcggtctgaa ctttccaatt ctgatgggag tccccacaca 480
ttctacgatg tatctctcta tgaagaagat ctgaacaacc tagctgatga cgaatggttg 540
aacgataata acgtctcgtt tatctacgag tacattgaaa gattttacat tacccgttgt 600
ttgagcgaca agcttcaatt ttcatcaaag aagatggtca attctcaaat aatactcctc 660
cgaccttcta tggttttttt gctggcacat tcaactccaa aagatatcca ggattttctc 720
ccaccgttgg ataagtctgg ctttatattc cttcctctga acgacaatga tgatctggaa 780
atggctgaag gtggatccca ttggtgtctt ttagttgtag ctgttcacga taacaaatgt 840
ttcctctatg actcattaga gaatgccaat ctcacagagt ctgttgcgct tgtgtctaag 900
ctgtccactc tgctaaacag gcgaatacaa ctcgttgaaa atacacattg tcctcaacaa 960
ctcaatggca gtgattgtgg agtaatcaca acccaaatta cagcactact ggtatcccga 1020
ctgctttgtg ttttgccggg acatcctata aatttggatc ttcaaaatgt agctatcaac 1080
gcaataagcg ggagaatctt catgttaaaa ctcctccaac atgttctgaa caattaa 1137
<210> 59
<211> 408
<212> DNA
<213> Pichia pastoris
<400> 59
atggcaccac cagtccctgt atatacgaga gatgaagtca agatgcaatt tccacagtac 60
atgatgaaat ttttgccttc aaactgtgag ctgtactcca tcatccagaa ccaatgtacc 120
ttctctgctg acgagataat atgtgtgccc ttcaagaggg tgtttgccaa atgccggagg 180
ggaaaccaag aagccaagag gaacataata ccagagaatg gaggactgaa tttaactgga 240
aagaaactaa tcccaagaga atacacagtc attgaagtta cggactccct aacgaacaag 300
tacgacaata gtagcctcat ggacagattt tttgaggcag aaagagattt aatgataagg 360
tttcaagaat atgaggaacg gaacagtaag gaaggagaaa taaagtag 408
<210> 60
<211> 1449
<212> DNA
<213> Pichia pastoris
<400> 60
atgctcagac agtttgctgg aagggagttc aagcgtcggt tttctacggg aatcaagacg 60
atgccaacaa agcttaccaa actgccaaat ggtattcgtg tcgtaacgga cgaagctccg 120
ggccatttta gtgccatggg cattttcgtt gatgctggtt caagatatga gagccagttt 180
ccagaattaa ccggccactc tcacatcatc gatagacttg cattcaaatc aacatccaaa 240
ttcgatggga aatctatggt agaaaacacc aatcatttag gtggcaactt tatgtgtgcc 300
tcttcaagag agtcattgat ataccaggct tcagtgttca acaaagatgt ggacaagatg 360
gctgaaatcc tcagttctac agtcaaagaa cctttattta ctgaggagga agtttctaat 420
cagatagcaa cagcagatta tgagttggat gagttatggc tgcaacctga cctaattctt 480
cccgaattgt ctcaacaggt agcttatgga tcaaaaaatt tgggttcccc gctgctctgt 540
ccgaaggagt ctttagcaaa catctcaaga gaatcccttt tgaagtatcg tgaaatattt 600
tttagacctg agaacttggt cgttgctatg ttgggagttc cccacgagaa ggccttggaa 660
cttgttgata aaaatttagg cgatatgaaa tctgtcggtt ccagtccagt ggtcaaagaa 720
cctgctaaat atacaggagg agaactttct ttgcctccag ttcctcctat gggtgggctt 780
cccgagtttc atcacatata tcttacattt gaaggtgtcc ccgtggactc tgacgatgtc 840
tactcactgg ctactttgca gatgctcgtc ggtggtggtg gatctttctc tgctggtggt 900
ccaggaaaag gaatgtatgc cagagcatac acgcgagttc tgaatcagta cggttttatt 960
gaaagttgca attcatatat acacaatttc tcagactcgg ggctgtttgg tctctcaatt 1020
tcaagcattc cgcaggcaaa taaagttgtt gcagaactct taggtcatga actgagctgc 1080
ttgttttctg aaaatccggg caaaggtgct cttaccaatg ccgaagtaaa ccgtgccaaa 1140
aatcagctac ggtcttcttt gttgatgaac ttggagagca agatggttca attagaagaa 1200
ctaggaagac acattcaagt ttatggcaga aaagttgatg tcacagagat gtgtgataaa 1260
atcagcaaag ttacaaagga agatctagtt gcaattgcaa agaaagtctt gaccggaagc 1320
aacccgacta tagttgttca aggtgacaga gaatcttatg gagacattga gggtactttg 1380
gcatcttttg gagttggttt agatgccgct tccaaagctt caaagaaaaa aacgagaggt 1440
tggttctaa 1449
<210> 61
<211> 390
<212> DNA
<213> Pichia pastoris
<400> 61
atggcaatta tcaagttcaa cgcaggcaaa gtcaagattg acgaggaaac caagctttgt 60
acacccttgg caacaagagg agaaataatc gtccaattgt cggctgaggg cgaagagttt 120
tatgatttca aatgggtccc tactgagaac acagctggtg aaggtaacca gtcagagaca 180
ttcttggtca ttccgggcga tgtgacgtgg aaacacgtca aaagttgtaa agatggtaga 240
gttttcaaat tgacattttt gagtagtggg gcaaagagtt tgttctggat gcaagatgat 300
aatggaaacg aggatgaccc atcagagttg acaaccaaag ataaggaaat tagtgaaaaa 360
attaccaagt tgttcgacga agaagagtga 390
<210> 62
<211> 2184
<212> DNA
<213> Pichia pastoris
<400> 62
atgaaacact tggctgtcca taagtacaag gtaggagcca tcgcagctgg cttggttgtc 60
tcctataaaa tctttgccta ccgcgctgcg tcttcctcct cctcaaacgt catcaacttg 120
accaatatgg caaaaactcc aatcacttta aaaccccctc aggctccact ccgctgggac 180
catactccag agcagatcct tgccgaaact gataagtata tatctaccag tcaagaggtt 240
gacgattggg tggcaaacag ctttgccact gccaatgtgg acaccatcaa gaaaatagcc 300
gccgctgaga atgaacaata cttgccactg tgtcaattga gtttttatca acatatctcg 360
gataaccagg acgttcgtaa tgccagtact gttagtgagg agaaaattga taagttctcc 420
atcgaatcca accttagaga agatgtgttc aaaacagtga acaaagtgtt caaacaggtt 480
caagaagatt cggaactcca aaagaccttg gacccagaat ttaggcgttt actagaaaaa 540
ttgaacctag gttacgtgag atctggttta gatttatccc aggagaagag agaccaagtc 600
aagagtttga aacaagaact atcaaccatt tcaatcaagt ttaataagaa cttgggagag 660
gaaactgaac acatttggtt caccactgag gagttaaaag gtgttccaga atcagttgtt 720
gagcagtttg aaactaagaa tgagaatgat gttacttacc acaagatgac atacaagtat 780
cctgacctgt tcccggtact aaaatatgcc gttaatccag ctacgagaca aagagctttt 840
gtcggggatc aaaacaagat acctgaaaat tcaggattac ttgtgaaagc cgtcaatttg 900
agaaacgaac ttgcaaaagt tttgggttat gatacctatg ctgactatat cctggaagtg 960
aagatggcca agaactccaa gaatgttttt gaatttcttg atgatgtaag ggaaaaactc 1020
agacctctcg gagagaagga actgcaaaga atgttgactc tcaaggctaa cgacccaaat 1080
gctgttgata aggaaaatta ctacgtctgg gatcatcgtt actatgataa caagcttctt 1140
gaatctgaat acaaagtgga tgagcaaaag ctggctgaat actttccaat ggagtccacc 1200
attgaaaaaa tgcttgccat ttacgagcac ttgttcaatt tgcagtttca acaagttgac 1260
gattcggaga aacaagtttg gcatccagat gtaaaacaat tctccgtttg gaaaatcgat 1320
aaccctgatt ctcctgaatt tgtgggctgg atctattttg atttgcatcc aagagaagga 1380
aaatacggtc acgctgctaa ttttggaatc ggtcctagtt acatcaaaga agatgggagt 1440
aaaaattatc ctgtcactgc tttggtttgc aacttttcta aaccatcaaa ggataagcca 1500
tccctattga agcacaatga agtcactaca ttcttccatg agctaggaca tggtatccat 1560
gatttaattg ggcaaactag gtatgctcgt ttccatggta cttcagttgc tcgtgatttc 1620
gttgaatgtc cttcacagat tctagagtac tggacctgga ctagagatca actcaagtct 1680
ctttcccaac attacaagac aggagaagcc ctctccgatg aactcattga ttcgctagtc 1740
aagtccaagc atgtcaatgg cgccattttc aatcttaggc agttacactt tggtctcttt 1800
gacatgaaac tacatactgc caaagagcct gaatctttag atgtgacaag gttgtggaac 1860
gaattacgtg aggaagtcgc tctggttaag aatggtgacc aaattacgaa aggatacggt 1920
tcatttggac acctaatggg cggttatgct gctggttact acggatacct gtattctcaa 1980
gtgtttgcca gtgacattta ttacaccttt ttcaaagctg atccaatgag tacagctcaa 2040
ggtatcaagt accgtgatat cattcttgcc agaggtggat caagagagga gctagataat 2100
ctcaaggaat tacttggaag agagcctaca tctgatgcct ttatgactga gcttggagta 2160
gaaaatggtg cgtccaagtt gtaa 2184
<210> 63
<211> 2766
<212> DNA
<213> Pichia pastoris
<400> 63
atgcgttttt tggtctcatc ctttcggccc ttcagacata caatttcgtc gcatatctca 60
atgggccagg ctctgtctgc cattcgtgta tttcataaaa attctcactc acgtacccaa 120
ggtttaaggc gccactctca ctactgttgc caccgcaaga tagatatgag tacttctact 180
aaacttccag agcgtcaatt gctaccagcc aatgttaggc ctaccaaata tgatttgaca 240
ttggagccct tattttctac cttcaagttt aacggagaag agactataca tttagatgtt 300
caggaggact ccagttctat tacgctacac gctctagaca tcgatctcca agattcacta 360
ttgataactt caaacaagtc taagactccc ccgcttcatg tgacaagcaa tgatgatgac 420
caatcgctca cttttcaatt caaagagggt actctagtaa agggagataa ggtgcagctg 480
cagttgaaat ttgttggtga attgaatgat aagatggccg gtttttaccg ctcttcatat 540
gaagagaatg gagaaactaa atatttggca actacccaga tggagccaac agattgtcgt 600
cgtgctttcc cttcctttga tgagccatcg ctaaaagccg tattcaacat tgccctcatt 660
gctgatcaga aacttacttg tctctcaaac atggacgtga aagaggaaca atctctcgga 720
gatagaagga agaaggtgat attcaatccc actccactaa tttctactta cctaattgct 780
tttattgttg gtgatttaaa atatattgaa gccgactata actatcgcat tcctgtcaga 840
gtttatgcca cccctggttt agagaagcag ggtcgttttt ctgtcgagct tgctgctaaa 900
acattagaat tctttgagca acagtttgat attgattatc ctcttccaaa gatggacatg 960
gtggcgattc atgatttcag tgcaggagct atggaaaact ttgggcttgt tacctataga 1020
gttgttgatt tgctgtacga tgaaaaaaat tcaaatttgg ctactaagca acgtgttgca 1080
gaagttgtcc aacacgaatt ggcgcatcag tggtttggta atcttgtcac aatggagtgg 1140
tgggagggcc tttggctgaa tgaaggcttt gctacatgga tgtcttggta ctcttgtgac 1200
aagtttttcc ctgattggaa agtatgggaa caatatgtta cagattcttt acaacaggct 1260
ctggctctgg acgctctacg tgcttctcac cctattgaag ttcctgtgaa aagggccgac 1320
gagatcaatc aaatttttga cgcaatttcc tattctaaag gatcctcctt gctaaaaatg 1380
atctccaaat ggctcggaga ggatgtgttc attaagggag tctccagtta tttaaaaaag 1440
cacaggtatg gtaatacgaa aaccaccgat ttgtgggaat cgctttctga ggtgtctgga 1500
aaagatgtgg tcaaagttat gagtatctgg actggtaaaa ttggatttcc aatcatctca 1560
gtaactgaaa atgcaaaccg tatcactttt actcagaaca gatatttaac tactggtgat 1620
gtaactcctg aagaggatac gacgatttat cctgtttttt tgggactcaa aacagaaagc 1680
tcaactgatg agtcgctggt ccttgactca aggtcaatgt cagtagatat ccagaattct 1740
gactttttca aagttaatgc tgaacaagcc ggtatttaca ggaccaatta tgcaccagag 1800
agatggatca aacttggaaa gcaacctcac cttctaagtg tagaagaccg tgctggtttg 1860
gttgcggatg cgggcgctct ggctagttct ggtcactcat ctacaaggaa ctttttgaac 1920
cttgtaaatt catggaaaga tgagtctagc tttgttgtct gggacgaaat aacttcccgt 1980
gttgcagctt taaaagcagc ttggttattt gaatcccaat ctgacattga cgccctgaat 2040
gctttcgtaa gagaccttat ttctacgaag atcaaaagta tcggatggtc attcaatgat 2100
aatgaaccat tccttgaaca aagactaaag agccttctat atgctactgc tgctggtgca 2160
aaagtaccag gagtagttaa atcagcattg ataaactttc aaaaatacgt tgctggtgat 2220
aagactgcca ttcaccctaa cataaaggca gttacgtttc aaactgttgc ggcccaagga 2280
tctgaaaagg aatgggatca gttactcgac atctacaaga accctgtatc tattgatgag 2340
aaaattattg ctcttaggtc tctcggaagg tttgaagatc ccatcttgat cgcaaagacc 2400
ctggcactgt tatttgatgg ttccgtaagg tcacaagata tttacgtacc aatgcaaggc 2460
cttcgtgcga ctaagatagg agtagagtca cttttcaagt ggttgactct taattgggac 2520
aagatttata aattgcttcc acctggtctg tcaatgcttg gttctgtggt tactatcagt 2580
acttctgggt tcacttcctt ggatgatcaa aagcgtgtca aagatttctt tgcatcaaag 2640
gataccaaag gcttcgacca gggtttggcc caggcgttag acaccatcca atccaaggca 2700
agttgggtac aacgtgactc taggaatgta tccgattggc tacgtgagca gggatacaaa 2760
aaatag 2766
<210> 64
<211> 1803
<212> DNA
<213> Pichia pastoris
<400> 64
atgataagga tatccttgct gaaaagagca ctgtttccct acgggcgact accaatgcat 60
aatggtaggt ggtattcaga cataggtggc ggaaattcaa ggaatcggaa cgaacagaaa 120
ccaaaattgc ctgtaccaac tagtaatgaa gttaaggaca atgagtcaaa cccggacttc 180
tttattaaaa acggctttag atcagctgat attgcagaga catcctttgt gaaagacaag 240
ggtgctacag tcgaagagga acgtaataca tcggacagtt cacacgaatc tcctcaactt 300
aattttaagg aaaccaacga cgaaacgaat tcaacgatcc aaccaccagt ggcaaaatta 360
cccaccccaa agcaattgaa acaatacctg gataggttca tcgtgggaca agagaagtgc 420
aagaagataa tgtcggtcgc agtttacact cattatgttc gaataaataa ccaggctcag 480
aaacggaatc agaaggtcga ttcctctgaa gaaaatgttg agaatgggtt tccaaatgtt 540
actaaagaat ttgaggacga aaatgaccca gattatgttc cggatttgga gaaatcaaat 600
gttcttttgc tgggaccgtc tggatcaggc aagaccctga ttgctaagac tctcgctaaa 660
tgtctgcagg ttccatttat aattcaagat tgtacctcct tgacccaggc tggttatgtt 720
ggcgaggata ttgagagctg tattgaaaag ttgctaattg attcagacta cgatattgaa 780
aggtgtgaaa agggaattat tgtgctggat gaaatagaca agttggccaa gccctctgtc 840
tatacaggaa ccaaagatat tgcaggagag ggtgttcaac aaggcctttt aaaactggtt 900
gaaggtacta cagttacggt tcaatgcaag aggagcaatg ctcctgatca taatcagttc 960
ggattgaatg gcaaagctac aaatcaggac aaggaaaatt atatcgttga cactacaaat 1020
atcttatttt taaccctggg agcgtttgtg aacctagata agattgttgc ttataggctg 1080
aagcagaact ctattggatt cgatactgat gagtcgaaag atatttctga aacagactca 1140
gtttccgaca aatctacatt agaatatgtt acacttccag atggatcaaa agtttcagct 1200
ctggaacttg tgtcttctac ggatctacag aattatgggt tgattccaga actgatcggc 1260
aggcttccga ttgtatcttc actttctcct ttaacagttg atgatcttgt ggctgtcctg 1320
actgagccca ggaactcgat actaaagcaa tatgtgcatt tctttgacac tgtcaatgtc 1380
aaacttgcta tcacttccaa ggcaatcaga aggatagccg agatctcgat caagaatggt 1440
acaggtgcaa gaggtctcag agccattttg gagaaactgc tactcaatgc caagtatgat 1500
tgccctggta gtagtatttc atttgtgtta gttgatacag atgttataag taagtctatc 1560
gatgagaata aggaaacggg ggaattcgtc ttcaaagatg gtgagccaaa gtattactcg 1620
cgtggagaat tattttcctt tttcaatgag ttatcaaaag aagacgaaaa actcaagaca 1680
tcaattgaaa agatgtgcca aataccactt tccaagaatc gcatagttta ctccgaagag 1740
gagcaggcaa ggttggattc ttctaaacct ctcgccgtga agcactatga acctttcatt 1800
tga 1803
<210> 65
<211> 2322
<212> DNA
<213> Pichia pastoris
<400> 65
atgagcttca acctgctaag tgttccttta cgaacgtcaa agccgatacc gttaggcgaa 60
agcctaaaag agcttatcaa caatcagtac taccagacat ctgctgcgtt caaatcggat 120
atcgaagaga tcgaccaact aagaaatgat gtcctatcaa tagaaccaaa caatgatgga 180
cttgcattgc tcaagagata ctatgtacag ttagccagca ttagccaaaa actccctgat 240
tattttatgg agtatccctg gtttggaaca ttaggatacc aagtaactgg ccccgtagct 300
ctaaaatccc tctatttcga aagaatcaat atagcgtaca acatcgcagc gacgtattca 360
atcataggtt taaacgagcc cagagctaca ggagaaggct tgaaaaaatc atgcatttat 420
tttcagtata gtagtggggc attcgaaagt gtactgaagc tagtggagca aaaaccgaaa 480
gagctgacac ttcccattga tcttagtgtt aacattatga aaaccctggc taaactcatg 540
ctggctcagg cccaggaatg tttttggcaa aaggctgttt ctaacacttt aaaagataac 600
gttattgcaa ggttggcctt tcaagtatct caattttacg atgaagctct gtctatggct 660
tacaagtgcg atattttaaa gtctgaatgg atagaacata tgagttgcaa gaagctgcat 720
tttaaggctg cggcccaatt tagacttgct tgtgtggcag tcgctgcttc tagacatgga 780
gaggaaatag caagattaag gattgcaaat accatttgcg aaacagcatc tagagaagcc 840
aagtatcacc ttccctctgt atcttccgat ttggagagtc tttcgaagat aatcaaagac 900
tctttaagaa gaagtgaacg tgataatgat ctaatatatc tgcaggaagt tcctaatgaa 960
tcagatcttc ctccaattgt tgcagcatct atggttgaac ctaagccaat agttgagtta 1020
aattcagctg aatgtgcgaa agatacaaag aaatacggca aaatcctttt ccatgatctt 1080
atgccatact tagtgattga aattgcacag gcatttagag agaggcagga ttcttatgtt 1140
gtaaagcata tcaaggagcc catggagatg ctgacaaaga ttcttcacac aatccttgct 1200
gaaaatggac ttccggcgtt gatagatacc atacaaaggc ctcaaagatt gccaaccaac 1260
atccttgaac attgtcaaat actcaatgaa aggggtggca tggacaaact taaggtattt 1320
ttcgaagata tcagcaagct aagacacaaa agtgagcaag ttctccaaaa ctgtgtcgaa 1380
ttgctacaaa tggaagagtc cgaaaatgag gaaatgagaa ggaagcatgg atcacagagg 1440
tggaattttg ctgactctag ggaggcatca gcagatgtca ggaaaagtgt acaggcacta 1500
gagggctatt tgaaacaggc ccatgatggt gatcaagtga tctggaatga cttcgaacaa 1560
ttgaagccac tactaagcat gatgagtgct cctaattcaa ctaaattact ggaagaattt 1620
gtaccaaatt caaaattcgt cagacttcct ccagaattga accgaatcgt taacgaatta 1680
agagctgatg ttaatcaggt caaaaagctc gcatcgcaaa gggaaacttt tattaataca 1740
gttaaagtaa aaagcaccga cctgtccata ttgcccttgg tagtttccca ttataagaaa 1800
ttacaacaaa acaacattaa tacgatcacg acggaattgt tcgaagaagt gttcagacga 1860
caggttagca acttcgattc tgatatcaga tttgttcaaa aacacaggga caaccaaatc 1920
gagttagaga agcatattaa atctttggtc caacaattca atcagcttag agggaatata 1980
gatgcctcgc aagaacgcca aaatgcactt cagttgttgg acgatgccta taacggatac 2040
cttgatttgg taaacaacct cacacaggga cttagttttt acaatgattt cactggaaag 2100
gcaaatgatg tctatttgag atgtcaagaa ttctacaact ttcgtaaaca agaagccatg 2160
aagctggagc aggaaatata tgctgtattt gaacaaggta aatctcctca gaaaaaacaa 2220
ctagaagatc aggtttcaga tcaaccaaaa agtgaagtca agtcttcaaa gggttattct 2280
aatgagctgt ggaaccccga cgttggaatt aaatttggct ag 2322
<210> 66
<211> 960
<212> DNA
<213> Pichia pastoris
<400> 66
atggtggcct ctcttcacat tgtcaatccg aatttggcct ccgctttcag tttgcctccc 60
aggtcaaaca ctttgagcgt ttccatacac gcttcggctt tgttacagat cctggaatca 120
agttacttcg accagaataa gaatggtcgt atcataggaa ccctcctagg ttctaggtct 180
gaagagacaa cggaggttca agtcaaagac tctttcatag tttcccacac ggaggacgga 240
gacgagttta ccattgattc ttctcaacgt gaatttgtcg ccatccacaa gaagtctagc 300
ccaagagact cagtcgtagg atggttttcc attaactcta aggtcgacag ctttatcgga 360
ctggtccatg actttttctc aaagggtcca gatagcacac acccgtaccc tgccatatat 420
ttgagtatcc agttatgtga cgagagcgga tccttcgtag agccagtttt caaggcgtac 480
gttgcctccc cagtgggatg ttatggagct ctggcaagtc acttagacct tgaaaaagct 540
ggctcttttg tcttctctga agtcccaacc aaggtcatat actctgctaa cgaaaaaagt 600
ctgctggctc atttcaagaa caacgttgtg gaacccaaag ttccaatacc acaaaacgac 660
acaaatcaac taatttcaca actcaacaaa ctcgacgttt ccattgacca gttaatagac 720
tacgttgaca aagtcatttc aggatctctg gatagaaatg atgtgaagaa tgatgagatt 780
ggccgtttcc tgttgaccaa cttagtttcc cttccaactt ctccttcaaa ggaagagctt 840
tcatcttcca taagctctca tatccaggac tcactgatga tcgactactt ggcctccgcc 900
gtgaaaactc aattagatgt tagctccaaa ttaatgaacc tggtacaaga tgataaatag 960
<210> 67
<211> 599
<212> PRT
<213> Pichia pastoris
<400> 67
Met Leu Lys Asp Gln Phe Leu Leu Trp Val Ala Leu Ile Ala Ser Val
1 5 10 15
Pro Val Ser Gly Val Met Ala Ala Pro Ser Glu Ser Gly His Asn Thr
20 25 30
Val Glu Lys Arg Asp Ala Lys Asn Val Val Gly Val Gln Gln Leu Asp
35 40 45
Phe Ser Val Leu Arg Gly Asp Ser Phe Glu Ser Ala Ser Ser Glu Asn
50 55 60
Val Pro Arg Leu Val Arg Arg Asp Asp Thr Leu Glu Ala Glu Leu Ile
65 70 75 80
Asn Gln Gln Ser Phe Tyr Leu Ser Arg Leu Lys Val Gly Ser His Gln
85 90 95
Ala Asp Ile Gly Ile Leu Val Asp Thr Gly Ser Ser Asp Leu Trp Val
100 105 110
Met Asp Ser Val Asn Pro Tyr Cys Ser Ser Arg Ser Arg Val Lys Arg
115 120 125
Asp Ile His Asp Glu Lys Ile Ala Glu Trp Asp Pro Ile Asn Leu Lys
130 135 140
Lys Asn Glu Thr Ser Gln Asn Lys Asn Phe Trp Asp Trp Leu Val Gly
145 150 155 160
Thr Ser Thr Ser Ser Pro Ser Thr Ala Thr Ala Thr Gly Ser Gly Ser
165 170 175
Gly Ser Gly Ser Gly Ser Gly Ser Gly Ser Ala Ala Thr Ala Val Ser
180 185 190
Val Ser Ser Ala Gln Ala Thr Leu Asp Cys Ser Thr Tyr Gly Thr Phe
195 200 205
Asp His Ala Asp Ser Ser Thr Phe His Asp Asn Asn Thr Asp Phe Phe
210 215 220
Ile Ser Tyr Ala Asp Thr Thr Phe Ala Ser Gly Ile Trp Gly Tyr Asp
225 230 235 240
Asp Val Ile Ile Asp Gly Ile Glu Val Lys Glu Leu Ser Phe Ala Val
245 250 255
Ala Asp Met Thr Asn Ser Ser Ile Gly Val Leu Gly Ile Gly Leu Lys
260 265 270
Gly Leu Glu Ser Thr Tyr Ala Ser Ala Ser Ser Val Ser Glu Met Tyr
275 280 285
Gln Tyr Asp Asn Leu Pro Ala Lys Met Val Thr Asp Gly Leu Ile Asn
290 295 300
Lys Asn Ala Tyr Ser Leu Tyr Leu Asn Ser Lys Asp Ala Ser Ser Gly
305 310 315 320
Ser Ile Leu Phe Gly Gly Val Asp His Glu Lys Tyr Ser Gly Gln Leu
325 330 335
Leu Thr Val Pro Val Ile Asn Thr Leu Ala Ser Ser Gly Tyr Arg Glu
340 345 350
Ala Ile Arg Leu Gln Ile Thr Leu Asn Gly Ile Asp Val Lys Lys Gly
355 360 365
Ser Asp Gln Gly Thr Leu Leu Gln Gly Arg Phe Ala Ala Leu Leu Asp
370 375 380
Ser Gly Ala Thr Leu Thr Tyr Ala Pro Ser Ser Val Leu Asn Ser Ile
385 390 395 400
Gly Arg Asn Leu Gly Gly Ser Tyr Asp Ser Ser Arg Gln Ala Tyr Thr
405 410 415
Ile Arg Cys Val Ser Ala Ser Asp Thr Thr Ser Leu Val Phe Asn Phe
420 425 430
Gly Gly Ala Thr Val Glu Val Ser Leu Tyr Asp Leu Gln Ile Ala Thr
435 440 445
Tyr Tyr Thr Gly Gly Ser Ala Thr Gln Cys Leu Ile Gly Ile Phe Ser
450 455 460
Ser Gly Ser Asp Glu Phe Val Leu Gly Asp Thr Phe Leu Arg Ser Ala
465 470 475 480
Tyr Val Val Tyr Asp Leu Asp Gly Leu Glu Val Ser Leu Ala Gln Ala
485 490 495
Asn Phe Asn Glu Thr Asp Ser Asp Val Glu Ala Ile Thr Ser Ser Val
500 505 510
Pro Ser Ala Thr Arg Ala Ser Gly Tyr Ser Ser Thr Trp Ser Gly Ser
515 520 525
Ala Ser Gly Thr Val Tyr Thr Ser Val Gln Met Glu Ser Gly Ala Ala
530 535 540
Ser Ser Ser Asn Ser Ser Gly Ser Asn Met Gly Ser Ser Ser Ser Ser
545 550 555 560
Ser Ser Ser Ser Ser Ser Thr Ser Ser Gly Asp Glu Glu Gly Gly Ser
565 570 575
Ser Ala Asn Arg Val Pro Phe Ser Tyr Leu Ser Leu Cys Leu Val Val
580 585 590
Ile Leu Gly Val Cys Ile Val
595
<210> 68
<211> 562
<212> PRT
<213> Pichia pastoris
<400> 68
Met Ile Ile Asn His Leu Val Leu Thr Ala Leu Ser Ile Ala Leu Ala
1 5 10 15
Asn Asp Tyr Glu Ser Leu Asp Leu Arg His Ile Gly Val Leu Tyr Thr
20 25 30
Ala Glu Ile Gln Ile Gly Ser Asp Glu Thr Glu Ile Glu Val Ile Val
35 40 45
Asp Thr Gly Ser Ala Asp Leu Trp Val Ile Asp Ser Asp Ala Ala Val
50 55 60
Cys Glu Leu Ser Tyr Asp Glu Ile Glu Ala Asn Ser Phe Ser Ser Ala
65 70 75 80
Ser Ala Lys Phe Met Asp Lys Ile Ala Pro Pro Ser Gln Glu Leu Leu
85 90 95
Asp Gly Leu Ser Glu Phe Gly Phe Ala Leu Asp Gly Glu Ile Ser Gln
100 105 110
Tyr Leu Ala Asp Lys Ser Gly Arg Val Ser Lys Arg Glu Glu Asn Gln
115 120 125
Gln Asp Phe Asn Ile Asn Arg Asp Glu Pro Val Cys Glu Gln Phe Gly
130 135 140
Ser Phe Asp Ser Ser Ser Ser Asp Thr Phe Gln Ser Asn Asn Ser Ala
145 150 155 160
Phe Gly Ile Ala Tyr Leu Asp Gly Thr Thr Ala Asn Gly Thr Trp Val
165 170 175
Arg Asp Thr Val Arg Ile Gly Asp Phe Ala Ile Ser Gln Gln Ser Phe
180 185 190
Ala Leu Val Asn Ile Thr Asp Asn Tyr Met Gly Ile Leu Gly Leu Gly
195 200 205
Pro Ala Thr Gln Gln Thr Thr Asn Ser Asn Pro Ile Ala Ala Asn Arg
210 215 220
Phe Thr Tyr Asp Gly Val Val Asp Ser Leu Arg Ser Gln Gly Phe Ile
225 230 235 240
Asn Ser Ala Ser Phe Ser Val Tyr Leu Ser Pro Asp Glu Asp Asn Glu
245 250 255
His Asp Glu Phe Ser Asp Gly Glu Ile Leu Phe Gly Ala Ile Asp Arg
260 265 270
Ala Lys Ile Asp Gly Pro Phe Arg Leu Phe Pro Tyr Val Asn Pro Tyr
275 280 285
Lys Pro Val Tyr Pro Asp Gln Tyr Thr Ser Tyr Val Thr Val Ser Thr
290 295 300
Ile Ala Val Ser Ser Ser Asp Glu Thr Leu Ile Ile Glu Arg Arg Pro
305 310 315 320
Arg Leu Ala Leu Ile Asp Thr Gly Ala Thr Phe Ser Tyr Leu Pro Thr
325 330 335
Tyr Pro Leu Ile Arg Leu Ala Phe Ser Ile His Gly Gly Phe Glu Tyr
340 345 350
Val Ser Gln Leu Gly Leu Phe Val Ile Arg Thr Ser Ser Leu Ser Val
355 360 365
Ala Arg Asn Lys Val Ile Glu Phe Lys Phe Gly Glu Asp Val Val Ile
370 375 380
Gln Ser Pro Val Ser Asp His Leu Leu Asp Val Ser Gly Leu Phe Thr
385 390 395 400
Asp Gly Gln Gln Tyr Ser Ala Leu Thr Val Arg Glu Ser Leu Asp Gly
405 410 415
Leu Ser Ile Leu Gly Asp Thr Phe Ile Lys Ser Ala Tyr Leu Phe Phe
420 425 430
Asp Asn Glu Asn Ser Gln Leu Gly Ile Gly Gln Ile Asn Val Thr Asp
435 440 445
Asp Glu Asp Ile Glu Val Val Gly Asp Phe Thr Ile Glu Arg Asp Pro
450 455 460
Ala Tyr Ser Ser Thr Trp Ser Ser Asp Leu Pro His Glu Thr Pro Thr
465 470 475 480
Arg Ala Leu Ser Thr Ala Ser Gly Gly Gly Leu Gly Thr Gly Ile Asn
485 490 495
Thr Ala Thr Ser Arg Ala Ser Ser Arg Ser Thr Ser Gly Ser Thr Ser
500 505 510
Arg Thr Ser Ser Thr Ser Gly Ser Ala Ser Gly Thr Ser Ser Gly Ala
515 520 525
Ser Ser Ala Thr Gln Asn Asp Glu Thr Ser Thr Asp Leu Gly Ala Pro
530 535 540
Ala Ala Ser Leu Ser Ala Thr Pro Cys Leu Phe Ala Ile Leu Leu Leu
545 550 555 560
Met Leu
<210> 69
<211> 207
<212> PRT
<213> Pichia pastoris
<400> 69
Met Val Ala Ser His Val Asn Asn Ala Ser Ala Ser Arg Ser Asn Thr
1 5 10 15
Ser Val Ser His Ala Ser Ala Ser Ser Tyr Asp Asn Lys Asn Gly Arg
20 25 30
Gly Thr Gly Ser Arg Ser Thr Thr Val Val Lys Asp Ser Val Ser His
35 40 45
Thr Asp Gly Asp Thr Asp Ser Ser Arg Val Ala His Lys Lys Ser Ser
50 55 60
Arg Asp Ser Val Val Gly Trp Ser Asn Ser Lys Val Asp Ser Gly Val
65 70 75 80
His Asp Ser Lys Gly Asp Ser Thr His Tyr Ala Tyr Ser Cys Asp Ser
85 90 95
Gly Ser Val Val Lys Ala Tyr Val Ala Ser Val Gly Cys Tyr Gly Ala
100 105 110
Ala Ser His Asp Lys Ala Gly Ser Val Ser Val Thr Lys Val Tyr Ser
115 120 125
Ala Asn Lys Ser Ala His Lys Asn Asn Val Val Lys Val Asn Asp Thr
130 135 140
Asn Ser Asn Lys Asp Val Ser Asp Asp Tyr Val Asp Lys Val Ser Gly
145 150 155 160
Ser Asp Arg Asn Asp Val Lys Asn Asp Gly Arg Thr Asn Val Ser Thr
165 170 175
Ser Ser Lys Ser Ser Ser Ser Ser His Asp Ser Met Asp Tyr Ala Ser
180 185 190
Ala Val Lys Thr Asp Val Ser Ser Lys Met Asn Val Asp Asp Lys
195 200 205
<210> 70
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 70
acctattgtt taccttcctg 20
<210> 71
<211> 40
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 71
gaattctctc acttaatctt tagctcccat gctcatcttg 40
<210> 72
<211> 40
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 72
gcggccgcaa gaagttgatt gtttatttgt aggcggtgcc 40
<210> 73
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 73
gggctatccg ccttatcttg 20
<210> 74
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 74
aataacttca tgactgcatt 20
<210> 75
<211> 40
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 75
gaattctctc acttaatctt agtttaaata atatggagat 40
<210> 76
<211> 40
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 76
gcggccgcaa gaagttgatt attggagaaa aggaatacac 40
<210> 77
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 77
ggcatctccg tctggtgcag 20
<210> 78
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 78
caaggttcga aactgcagct 20
<210> 79
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 79
ctcacttaat cttctgtact ctgaagagag agcaaaccaa tggcaa 46
<210> 80
<211> 47
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 80
agaagttgat tgagactttc aacgagggtc ctttggcaat cattggt 47
<210> 81
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 81
accccaggac caggtatttc 20
<210> 82
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 82
tactacaggc tggctgttcc 20
<210> 83
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 83
ctcacttaat cttctgtact ctgaagaagt ccaactgttg aacgcc 46
<210> 84
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 84
agaagttgat tgagactttc aacgagggtc cccttcagct accttt 46
<210> 85
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 85
tccctgctaa gccctaatcg 20
<210> 86
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 86
aagttgtatg gccgtcctca 20
<210> 87
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 87
ctcacttaat cttctgtact ctgaagtgag tcttggttgt gtcggt 46
<210> 88
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 88
agaagttgat tgagactttc aacgaggcct cctgtttgat cggttc 46
<210> 89
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 89
gtgccatggt gacgttacag 20
<210> 90
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 90
cggagttata ggggacgctt 20
<210> 91
<211> 47
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 91
ctcacttaat cttctgtact ctgaagcgtc acatcatagc cgttctc 47
<210> 92
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 92
agaagttgat tgagactttc aacgagcgtc aaaagtggtc gtggac 46
<210> 93
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 93
tggcccagtt acacggaata 20
<210> 94
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 94
gtcgatcgtt ggtgtgtgac 20
<210> 95
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 95
ctcacttaat cttctgtact ctgaaggagc cgactttgac atcgac 46
<210> 96
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 96
agaagttgat tgagactttc aacgagagcg aagagactgg ttccaa 46
<210> 97
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 97
agctgttcta accgtcctca 20
<210> 98
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 98
cttggaatat ctgtgggcgc 20
<210> 99
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 99
ctcacttaat cttctgtact ctgaagtcat gaccagcagt tgttca 46
<210> 100
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 100
agaagttgat tgagactttc aacgagatgc tgcaggaagg aacact 46
<210> 101
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 101
caaactctgc acctccaagc 20
<210> 102
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 102
ctctgattgc acgagaaggc 20
<210> 103
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 103
ctcacttaat cttctgtact ctgaagtgaa aggcgattgg agttgc 46
<210> 104
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 104
agaagttgat tgagactttc aacgagctgg ctctgcttct ggtact 46
<210> 105
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 105
gatgttgagg cgggcataag 20
<210> 106
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 106
tttcaacggg gttctacgga 20
<210> 107
<211> 48
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 107
ctcacttaat cttctgtact ctgaaggtgg tagtatgtgt gttggtgt 48
<210> 108
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 108
agaagttgat tgagactttc aacgagctgc gctttcaagt actgca 46
<210> 109
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 109
tgtcttcctc gtcttcctcg 20
<210> 110
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 110
cgggcaataa tcagtggagc 20
<210> 111
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 111
ctcacttaat cttctgtact ctgaagcgtt ggaggtaatg catggg 46
<210> 112
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 112
agaagttgat tgagactttc aacgagggcg gaccgtgtat tagaga 46
<210> 113
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 113
tcagagaagc cagtggaagg 20
<210> 114
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 114
ttcctcggcc tctttatgct 20
<210> 115
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 115
ctcacttaat cttctgtact ctgaagcaac gtggctaact ccttgg 46
<210> 116
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 116
agaagttgat tgagactttc aacgaggttg tcgacggcat tgaaga 46
<210> 117
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 117
tcggttcaaa gcccctaagt 20
<210> 118
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 118
aggtgtgaaa tgcgctgatc 20
<210> 119
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 119
ctcacttaat cttctgtact ctgaagaaac caacaacgcc tggtac 46
<210> 120
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 120
agaagttgat tgagactttc aacgagtcac aggctgaagg atcgaa 46
<210> 121
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 121
ccatggtgtg ttttccggtt 20
<210> 122
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 122
tgagggacaa agtaatgggg t 21
<210> 123
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 123
ctcacttaat cttctgtact ctgaagaccg aagtcatggt tggaaa 46
<210> 124
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 124
agaagttgat tgagactttc aacgagctac cgcagacaac ccattc 46
<210> 125
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 125
cgctccctca tcgagtactt 20
<210> 126
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 126
cagacatcgt ggaaactgcc 20
<210> 127
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 127
ctcacttaat cttctgtact ctgaagtatc tgcttcgatc cctgca 46
<210> 128
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 128
agaagttgat tgagactttc aacgagttct cccgtccagt tagcag 46
<210> 129
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 129
atttcagaag ctccgcatcc 20
<210> 130
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 130
acaaaagcac gcgattgaga 20
<210> 131
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 131
ctcacttaat cttctgtact ctgaagacac tcacggttgt ttgcaa 46
<210> 132
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 132
agaagttgat tgagactttc aacgagaacc ccaacaagcg gctata 46
<210> 133
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 133
acccggatct gctagtgaag 20
<210> 134
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 134
cgtatgctcg tgtgactgtg 20
<210> 135
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 135
ctcacttaat cttctgtact ctgaagttcc tatgcctggc gatgat 46
<210> 136
<211> 49
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 136
agaagttgat tgagactttc aacgagaggg agtcttgtat agttgagca 49
<210> 137
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 137
agcaggggta ttttcacgga 20
<210> 138
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 138
agcatgattg tgttgggtgg 20
<210> 139
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 139
ctcacttaat cttctgtact ctgaagaatc cgatactgta gccccg 46
<210> 140
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 140
agaagttgat tgagactttc aacgaggcaa agaaaactgg ccacac 46
<210> 141
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 141
ggaaggccct attcacgact 20
<210> 142
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 142
caccatttcc ctgctgtgtc 20
<210> 143
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 143
ctcacttaat cttctgtact ctgaagtcaa taccgaagac tccgca 46
<210> 144
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 144
agaagttgat tgagactttc aacgagggga ggtattcagg aggcat 46
<210> 145
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 145
gctcgatcag atattgtccg c 21
<210> 146
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 146
agcagctctc caatcagtgt 20
<210> 147
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 147
ctcacttaat cttctgtact ctgaagctgg aattgtgatc ccgctg 46
<210> 148
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 148
agaagttgat tgagactttc aacgagtttt gaagcaagcc tacccc 46
<210> 149
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 149
caggatccag ccgctaaaac 20
<210> 150
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 150
tgaacaagca gccacatcac 20
<210> 151
<211> 47
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 151
ctcacttaat cttctgtact ctgaagtgag ggccattctg acatact 47
<210> 152
<211> 48
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 152
agaagttgat tgagactttc aacgaggtga ggtatttaac tgcacgag 48
<210> 153
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 153
tcgcctacat agtctgcaca 20
<210> 154
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 154
acctcatgcc atgtctgtca 20
<210> 155
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 155
ctcacttaat cttctgtact ctgaagttga ctgccgcttc aaagtc 46
<210> 156
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 156
agaagttgat tgagactttc aacgagccgc cagagaattt gtgctt 46
<210> 157
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 157
tagaggtgaa cgtttggcct 20
<210> 158
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 158
aatccatcac ctccacccag 20
<210> 159
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 159
ctcacttaat cttctgtact ctgaaggctg ctggagtaaa aggtcc 46
<210> 160
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 160
agaagttgat tgagactttc aacgagcaag cagcaaccat ctacgg 46
<210> 161
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 161
aacctcatcc actgtcagca 20
<210> 162
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 162
ggaagacaaa gttcgctccg 20
<210> 163
<211> 48
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 163
ctcacttaat cttctgtact ctgaagtcat agttgagagc ctccttgt 48
<210> 164
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 164
agaagttgat tgagactttc aacgagacaa tgcactagga cgggat 46
<210> 165
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 165
cttgaatcag gcgacgtacc 20
<210> 166
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 166
cccagctctc tttcactcca 20
<210> 167
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 167
ctcacttaat cttctgtact ctgaagttga agagcagcag agtcga 46
<210> 168
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 168
agaagttgat tgagactttc aacgagttaa ttgcccacag tgtcgc 46
<210> 169
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 169
accttccaca gtcgacgaat 20
<210> 170
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 170
acaaacagtc aaatgcacgg a 21
<210> 171
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 171
ctcacttaat cttctgtact ctgaagtcct tccacctttc caacgt 46
<210> 172
<211> 47
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 172
agaagttgat tgagactttc aacgaggggg tagagaagtt agggagg 47
<210> 173
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 173
ggaactacaa ctggaggcct 20
<210> 174
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 174
tagtgccggt tccatggatt 20
<210> 175
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 175
ctcacttaat cttctgtact ctgaagggtc tatgggttga tgcgga 46
<210> 176
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 176
agaagttgat tgagactttc aacgagatgt gttgctcgct ctaggt 46
<210> 177
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 177
cgacaaacac accaaggtcc 20
<210> 178
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 178
gttgttggag tgagcgatgg 20
<210> 179
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 179
ctcacttaat cttctgtact ctgaagcctc cgttgatact cccgat 46
<210> 180
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 180
agaagttgat tgagactttc aacgagtgca ttcaaggctg gcaaat 46
<210> 181
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 181
gcatatggag tggtgtgcag 20
<210> 182
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 182
cgggtagcat tgaacgtacg 20
<210> 183
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 183
ctcacttaat cttctgtact ctgaagatgc tacggtaaac acccca 46
<210> 184
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 184
agaagttgat tgagactttc aacgagactg gagaaagctt ggtcga 46
<210> 185
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 185
aggcaccaga agaaagagct 20
<210> 186
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 186
ggacacgttt ggagcttctt 20
<210> 187
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 187
ctcacttaat cttctgtact ctgaaggccc accaattcag caactt 46
<210> 188
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 188
agaagttgat tgagactttc aacgaggatg ctggtcacat ggttcc 46
<210> 189
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 189
aaccgccaat agtttcagcc 20
<210> 190
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 190
ggatgagaaa gcggcttctg 20
<210> 191
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 191
ctcacttaat cttctgtact ctgaaggtgc caaaagtctg atccgg 46
<210> 192
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 192
agaagttgat tgagactttc aacgagtgcc acttcgttct ttgacg 46
<210> 193
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 193
acggatcagt gatggcgtat 20
<210> 194
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 194
atgggatctg gacgacgttt 20
<210> 195
<211> 47
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 195
ctcacttaat cttctgtact ctgaagagct ggatcacaaa cattcgg 47
<210> 196
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 196
agaagttgat tgagactttc aacgagcttt gagtgttggt ccctgc 46
<210> 197
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 197
cggctaccaa gtcagacctt 20
<210> 198
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 198
gttgcccatt acgtcctgtg 20
<210> 199
<211> 49
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 199
ctcacttaat cttctgtact ctgaagcctt tgatctttgg tgcatcttg 49
<210> 200
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 200
agaagttgat tgagactttc aacgagcact acagctggga acgaga 46
<210> 201
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 201
acgggttgga aaagttgagc 20
<210> 202
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 202
agtggggttg gagattggag 20
<210> 203
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 203
ctcacttaat cttctgtact ctgaagacga ttccagcata gcctgt 46
<210> 204
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 204
agaagttgat tgagactttc aacgagctgg tagccgcaaa acttca 46
<210> 205
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 205
gcgttgaatc ctcctcgttc 20
<210> 206
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 206
ctgtggggtc tgaacatcct 20
<210> 207
<211> 47
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 207
ctcacttaat cttctgtact ctgaagagct gctagggttc attgagt 47
<210> 208
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 208
agaagttgat tgagactttc aacgagctcc cttgggtacg tcaact 46
<210> 209
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 209
tggcagtctt cacatgtcct 20
<210> 210
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 210
agctggtcaa gtctggtacc 20
<210> 211
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 211
ctcacttaat cttctgtact ctgaaggagg tctagtgtgt gaggct 46
<210> 212
<211> 49
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 212
agaagttgat tgagactttc aacgagagaa ggtataggga atatgcggt 49
<210> 213
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 213
tagccacaac cctgatgacg 20
<210> 214
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 214
tacactggga cgcagatgtt 20
<210> 215
<211> 48
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 215
ctcacttaat cttctgtact ctgaagtgct caaactctgt atccgttg 48
<210> 216
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 216
agaagttgat tgagactttc aacgagcttt caaggccgca atgcta 46
<210> 217
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 217
cttcctttgc agttggtggt 20
<210> 218
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 218
gggtctttgg ctttggtgag 20
<210> 219
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 219
ctcacttaat cttctgtact ctgaagcgtc tctggaactc gtcgat 46
<210> 220
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 220
agaagttgat tgagactttc aacgagcccc aagtcaagga ggagtt 46
<210> 221
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 221
gagtccaatc acggccaatc 20
<210> 222
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 222
tgcttcttcg gacagatcgt 20
<210> 223
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 223
ctcacttaat cttctgtact ctgaagtact gattgaaggg tcggca 46
<210> 224
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 224
agaagttgat tgagactttc aacgagttgt acggaccagg aagcat 46
<210> 225
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 225
ttcctctgcc tcttccttgg 20
<210> 226
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 226
agcatgcaaa cacgaggtac 20
<210> 227
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 227
ctcacttaat cttctgtact ctgaagagag gaaaacgagc ttgggt 46
<210> 228
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 228
agaagttgat tgagactttc aacgagatca aggttgccag cgaatg 46
<210> 229
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 229
accctacaga accgcaatga 20
<210> 230
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 230
acagcccaaa tagagacgca 20
<210> 231
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 231
ctcacttaat cttctgtact ctgaagagga gcccagtttt acgtca 46
<210> 232
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 232
agaagttgat tgagactttc aacgagtatc ccgcggtgaa gactac 46
<210> 233
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 233
gtgttgctaa gcctgtggac 20
<210> 234
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 234
tcctcctttc gacgcttctt 20
<210> 235
<211> 49
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 235
ctcacttaat cttctgtact ctgaagacag ctgtgaatca tgaagtttt 49
<210> 236
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 236
agaagttgat tgagactttc aacgagattc tcactggcag aacgga 46
<210> 237
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 237
ttttcacgtt gaggccactg 20
<210> 238
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 238
agctccgcag taacaggaat 20
<210> 239
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 239
ctcacttaat cttctgtact ctgaagtcaa agcaacttat ggcggt 46
<210> 240
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 240
agaagttgat tgagactttc aacgagctct tcgcagcacc agaaag 46
<210> 241
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 241
tcgttgttgc tggtgttctg 20
<210> 242
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 242
agtttgaagg cacgttggtc 20
<210> 243
<211> 47
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 243
ctcacttaat cttctgtact ctgaagactc caacaggact ttgaggt 47
<210> 244
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 244
agaagttgat tgagactttc aacgagaaat gtggaagttg cagcgg 46
<210> 245
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 245
aggttgatcg ccgtcttgta 20
<210> 246
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 246
tcttcatgag gtggtaggcg 20
<210> 247
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 247
ctcacttaat cttctgtact ctgaagagag ggcagatgac ataccg 46
<210> 248
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 248
agaagttgat tgagactttc aacgaggaga aactggaggt gctcgt 46
<210> 249
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 249
caaggcattc agttgaccgt 20
<210> 250
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 250
accaacgagc cttacagaca 20
<210> 251
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 251
ctcacttaat cttctgtact ctgaagtttt gaccgtcagt gcatgg 46
<210> 252
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 252
agaagttgat tgagactttc aacgaggtcg gaggtgtgag aattga 46
<210> 253
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 253
tgggaactat gtggctcctc 20
<210> 254
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 254
cgagctatca gtactcccgg 20
<210> 255
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 255
ctcacttaat cttctgtact ctgaagggtt ctcagctgtc cgagat 46
<210> 256
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 256
agaagttgat tgagactttc aacgagtagc attgcccatc acaacg 46
<210> 257
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 257
gtgggaagac tattgatgcg a 21
<210> 258
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 258
gggaaatcgc tgaggtgtac 20
<210> 259
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 259
ctcacttaat cttctgtact ctgaagaggt catctggaag ctttgc 46
<210> 260
<211> 49
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 260
agaagttgat tgagactttc aacgagggtg gccaatggta ttactttga 49
<210> 261
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 261
ataagagccc cgatacaggc 20
<210> 262
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 262
cttgacacac tttgctcctg a 21
<210> 263
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 263
ctcacttaat cttctgtact ctgaagagta gctgacctgt tgtgcc 46
<210> 264
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 264
agaagttgat tgagactttc aacgagggac accatatgat gcccga 46
<210> 265
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 265
cagatcaagt ccaagtccgc 20
<210> 266
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 266
agagactttg cgagagtccc 20
<210> 267
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 267
ctcacttaat cttctgtact ctgaagtgca atatccaaac acgcca 46
<210> 268
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 268
agaagttgat tgagactttc aacgagactt ctggaatctt cgggca 46
<210> 269
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 269
ggatgtttgg gccattgtga 20
<210> 270
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 270
caatctctcg cttcatcacg 20
<210> 271
<211> 49
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 271
ctcacttaat cttctgtact ctgaagtcgc tgttaaccat aattctttg 49
<210> 272
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 272
agaagttgat tgagactttc aacgaggcga gggttgagga gatttt 46
<210> 273
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 273
ggccatggca ctattttgtt 20
<210> 274
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 274
acgtacttcc cgcccaataa 20
<210> 275
<211> 47
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 275
ctcacttaat cttctgtact ctgaagccca cctaaatttc gagtgca 47
<210> 276
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 276
agaagttgat tgagactttc aacgagacac tttcgcagct tttggt 46
<210> 277
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 277
tcctccttgc catgaagagg 20
<210> 278
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 278
gcctgatgaa gatgatgccg 20
<210> 279
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 279
ctcacttaat cttctgtact ctgaagaggc tcagtcacct ctatga 46
<210> 280
<211> 47
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 280
agaagttgat tgagactttc aacgagtgat caagaacacc gtcgaag 47
<210> 281
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 281
tccctttgtt ggtcgtacga 20
<210> 282
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 282
tggttcaact tgtagcgcat 20
<210> 283
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 283
ctcacttaat cttctgtact ctgaaggggc ttgctcaact tttgga 46
<210> 284
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 284
agaagttgat tgagactttc aacgagcgac aatctggtag cgcatc 46
<210> 285
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 285
atgctcgtac aaagacccca 20
<210> 286
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 286
tgagatctcc aagtgcagca 20
<210> 287
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 287
ctcacttaat cttctgtact ctgaaggacg gtcgatttgg ctcatc 46
<210> 288
<211> 49
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 288
agaagttgat tgagactttc aacgagtgaa gaagctcaac actctgaac 49
<210> 289
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 289
tgattgacgg caccctgtat 20
<210> 290
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 290
caataattca gctgcgccct 20
<210> 291
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 291
ctcacttaat cttctgtact ctgaagcctc tgtagctgct tgtcct 46
<210> 292
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 292
agaagttgat tgagactttc aacgagagga gtcagtcggt ccaaag 46
<210> 293
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 293
tgtgggctgg gatgtgtaat 20
<210> 294
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 294
agcacggtca agtaaatcgc 20
<210> 295
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 295
ctcacttaat cttctgtact ctgaagtgct atcactgatt tgccca 46
<210> 296
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 296
agaagttgat tgagactttc aacgagggag attcccggca agtatc 46
<210> 297
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 297
ggctttctga ctacctgggt 20
<210> 298
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 298
aaagggaaga agggtgcagt 20
<210> 299
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 299
ctcacttaat cttctgtact ctgaagaagg tcgactcggg aaacat 46
<210> 300
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 300
agaagttgat tgagactttc aacgagtggt atcccgactg ctttgt 46
<210> 301
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 301
tggaatggct cgagaatggt 20
<210> 302
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 302
accaacaggc tgaacactag a 21
<210> 303
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 303
ctcacttaat cttctgtact ctgaagtcgt cagcagagaa ggtaca 46
<210> 304
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 304
agaagttgat tgagactttc aacgagacgg actccctaac gaacaa 46
<210> 305
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 305
tctgatggtt ggctttgctt 20
<210> 306
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 306
cggtttgtgg cccatctatg 20
<210> 307
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 307
ctcacttaat cttctgtact ctgaagaaaa ccgacgcttg aactcc 46
<210> 308
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 308
agaagttgat tgagactttc aacgagaagt cttgaccgga agcaac 46
<210> 309
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 309
gggccttaac aaacaccaca 20
<210> 310
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 310
tagaggcgga aaggaacgag 20
<210> 311
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 311
ctcacttaat cttctgtact ctgaagttgc caagggtgta caaagc 46
<210> 312
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 312
agaagttgat tgagactttc aacgagacca agttgttcga cgaaga 46
<210> 313
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 313
caacacatac caggcgaagg 20
<210> 314
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 314
ccctcctccg ccatcattat 20
<210> 315
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 315
ctcacttaat cttctgtact ctgaagtagg agacaaccaa gccagc 46
<210> 316
<211> 47
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 316
agaagttgat tgagactttc aacgagggag tagaaaatgg tgcgtcc 47
<210> 317
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 317
aatggctcca aatcacaggc 20
<210> 318
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 318
gctttgagga atgcgtgaag a 21
<210> 319
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 319
ctcacttaat cttctgtact ctgaaggtag tgagagtggc gcctta 46
<210> 320
<211> 47
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 320
agaagttgat tgagactttc aacgagtggg tacaacgtga ctctagg 47
<210> 321
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 321
acactcttaa ggctcgtcgt 20
<210> 322
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 322
ctcctccact tcagtatccg t 21
<210> 323
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 323
ctcacttaat cttctgtact ctgaagttcc ttgaatttcc gccacc 46
<210> 324
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 324
agaagttgat tgagactttc aacgaggagc aggcaaggtt ggattc 46
<210> 325
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 325
ctgggcagca aataacggtt 20
<210> 326
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 326
ccaaagttgg ctccgagtag 20
<210> 327
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 327
ctcacttaat cttctgtact ctgaagccta acggtatcgg ctttga 46
<210> 328
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 328
agaagttgat tgagactttc aacgagggca aaatcctttt ccatga 46
<210> 329
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 329
gaagaaggcc aagtgtgata 20
<210> 330
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 330
gacgagacgc tgttcctttc 20
<210> 331
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 331
ctcacttaat cttctgtact ctgaagtgtg aagagaggcc accatt 46
<210> 332
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 332
agaagttgat tgagactttc aacgagtgat cgactacttg gcctcc 46
<210> 333
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 333
aacaacattc aagctgccgt 20
<210> 334
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 334
atcggcaaag atgaagcgac 20
<210> 335
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 335
gctggacact tctgagctca 20
<210> 336
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 336
acttgtcagg acgatacgga 20
<210> 337
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 337
ccggtctccc tggaaataga 20
<210> 338
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 338
gcgaggtcct tgtcaatgag 20
<210> 339
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 339
acaagaactc gggctccttt 20
<210> 340
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 340
ttgcagcgct ccataatgtc 20
<210> 341
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 341
gctgattctg agaacgctgg 20
<210> 342
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 342
gccattcttc ggtgcagtag 20
<210> 343
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 343
tagagttgtc ccaaacggca 20
<210> 344
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 344
cgtggttctc gaggctctat 20
<210> 345
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 345
ggagttggaa cgtcgtagga 20
<210> 346
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 346
agttgtccgt cattagccct 20
<210> 347
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 347
tgttcccttt cggctagaca 20
<210> 348
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 348
acggttgagg gcattacgta 20
<210> 349
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 349
ttgtcttcca ccccttcgtt 20
<210> 350
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 350
ggttggcctt ggacattgtt 20
<210> 351
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 351
tgctcttcgg tactcatgct 20
<210> 352
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 352
tttggccatg ctgagctttt 20
<210> 353
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 353
aagcccgatc acttgcattt 20
<210> 354
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 354
cacctaatgt ttggcacccc 20
<210> 355
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 355
atcccagact gacatcgcaa 20
<210> 356
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 356
ccgccagaaa ttcatgccat 20
<210> 357
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 357
tcgtttcact gtaccatgca 20
<210> 358
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 358
accagtccgc attttcactg 20
<210> 359
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 359
gtggacagct gcaatcgtag 20
<210> 360
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 360
caactgggaa gcctgcattt 20
<210> 361
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 361
ccttgcatat ccgtttgcca 20
<210> 362
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 362
ggaggttcag gagcaggaat 20
<210> 363
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 363
cggtttcatc tgttgcctcc 20
<210> 364
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 364
gtcgcccatg ttctttcgat 20
<210> 365
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 365
caaacaggct ggaaaccaca 20
<210> 366
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 366
aatctccacg ttcagttgcg 20
<210> 367
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 367
tcatcccttg aaaaccccga 20
<210> 368
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 368
ttgtggaggg agattcaggc 20
<210> 369
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 369
aaggtaagga acgtgcttgc 20
<210> 370
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 370
gttctactgt tcacgtgctc t 21
<210> 371
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 371
accggttaga atacatgctg c 21
<210> 372
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 372
cgaaaagaag ctggactccg 20
<210> 373
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 373
ttccatcgta cgaccagtgt 20
<210> 374
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 374
agcgatgagg ccaacagtat 20
<210> 375
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 375
tgtccagccc aaaagactga 20
<210> 376
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 376
ctcctggggc tcgtactaag 20
<210> 377
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 377
cctcaataac gacggccttg 20
<210> 378
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 378
ccttttcctg atcagtgggg 20
<210> 379
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 379
tgttggggaa tgaaacacga 20
<210> 380
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 380
gaaggacgag tagggttgct 20
<210> 381
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 381
tcctgatctg gctcgtttgt 20
<210> 382
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 382
acctccaact cctgaaagca 20
<210> 383
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 383
cctcgagtct gggctttaca 20
<210> 384
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 384
ggagagatgc cagaccaagt 20
<210> 385
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 385
agcctgttct actgcatacg t 21
<210> 386
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 386
ccatttcttg taccctgggc 20
<210> 387
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 387
gcagaaaagg cgcgaatttc 20
<210> 388
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 388
gggaaaggat gtggaccaac 20
<210> 389
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 389
tggccaagag tgtccaattg 20
<210> 390
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 390
taacagatgg cgcacgtaga 20
<210> 391
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 391
ccttgcgttc ccaggtaaag 20
<210> 392
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 392
tgtggtatgg tttggggcta 20
<210> 393
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 393
actcccgttc ctccatgttc 20
<210> 394
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 394
acggtacaaa aggcgtttca 20
<210> 395
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 395
agtcaaactc ggtggtaggt 20
<210> 396
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 396
cggttatcat gtgcctgctc 20
<210> 397
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 397
atgttgctgc tccgaaatcc 20
<210> 398
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 398
gatctgctgg ccttgagagt 20
<210> 399
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 399
ctatgtcctg gtgtttgccg 20
<210> 400
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 400
gccaatgatg atctcgcagg 20
<210> 401
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 401
gcctttgata tgccgtcgtt 20
<210> 402
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 402
tcgagtaatg cttcccacca 20
<210> 403
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 403
agctttcaca acagcgatcg 20
<210> 404
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 404
tgattgcttc tgggttgctg 20
<210> 405
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 405
caaaaccggc gtaaaatggc 20
<210> 406
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 406
ttgtgctgca tctgtgtgag 20
<210> 407
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 407
agcctacaag tggttacagg t 21
<210> 408
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 408
ggaaaccgac cagcctaaag 20
<210> 409
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 409
agtcgcacca ggttatcaca 20
<210> 410
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 410
ggaaagctgc ccagaaactc 20
<210> 411
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 411
tgagaggatt cgttgtggct 20
<210> 412
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 412
ctatgtcgaa gtagcggtgc 20
<210> 413
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 413
agagtggcac tgctatcgaa 20
<210> 414
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 414
cgtacaaact tggcagctgt 20
<210> 415
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 415
gctgtgttgt aaattccggc 20
<210> 416
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 416
acaacccgga agacaactct 20
<210> 417
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 417
tgtcgttgcc ttcccgatat 20
<210> 418
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 418
gaagatggga gagggtgctt 20
<210> 419
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 419
cttgttgacg acggtagcag 20
<210> 420
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 420
ccctagtctc gttcgaaggg 20
<210> 421
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 421
ggcacagcag gttttcgtat 20
<210> 422
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 422
ggagattctg atgctacccc a 21
<210> 423
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 423
tggagccatc agatcaggac 20
<210> 424
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 424
cctgttcttg caagccttca 20
<210> 425
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 425
taagacatgc gaccaccaga 20
<210> 426
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 426
catggccaat gtcgaactgt 20
<210> 427
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 427
agctggctga aaaggtgttg 20
<210> 428
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 428
ctcagtgttg gaaagcaccc 20
<210> 429
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 429
tagggaatct ttggtggcgt 20
<210> 430
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 430
ggaacctaga gcgagcaaca 20
<210> 431
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 431
caggctctat tgtcgacgtg 20
<210> 432
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 432
ggaggtgatg acaatgccac 20
<210> 433
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 433
ctgtgaagct cctcctacgt 20
<210> 434
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 434
ggacactgct ggacaagaga 20
<210> 435
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 435
tactgacgcc gaagagctag 20
<210> 436
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 436
ccgatcgcaa aatagtggca 20
<210> 437
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 437
gttgtggttg tatgcggtca 20
<210> 438
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 438
caataactcc actggtgccg 20
<210> 439
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 439
tcgttatact ccagcgtgct 20
<210> 440
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 440
gggctcaaaa tctggaacca 20
<210> 441
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 441
caatgcagta ctcaccggtg 20
<210> 442
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 442
aagctgacga ccccttagac 20
<210> 443
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 443
ctatcgtgtc tgggctgcta 20
<210> 444
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 444
aaggagattg ccgcaactct 20
<210> 445
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 445
gtggagtcag agtcgagagg 20
<210> 446
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 446
cccagctttt atacggcttg g 21
<210> 447
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 447
cagcaaaagc tcgtgatcca 20
<210> 448
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 448
tgcgggtagt cgattgatgt 20
<210> 449
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 449
tcacgtatct cagcaacagg a 21
<210> 450
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 450
ggacctagga aatacgccca 20
<210> 451
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 451
actccagttc cacaagtcca 20
<210> 452
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 452
actgccaacc gtttactcca 20
<210> 453
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 453
gcgcggaaga ttaaagtcgt 20
<210> 454
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 454
ttggactcga tcgatgaggg 20
<210> 455
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 455
tgatgacttc caagatgcgc 20
<210> 456
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 456
tcacctggag caactgatgt 20
<210> 457
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 457
gtttggtacg cttgtaggcc 20
<210> 458
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 458
gatgagcaag catccattca 20
<210> 459
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 459
aaagacagga gcgtgagcat 20
<210> 460
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 460
ctcaacttcg cttgcccttt 20
<210> 461
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
primer
<400> 461
tgggaaacag aacgatgaac t 21
<210> 462
<211> 2835
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 462
ggtggttacg gtccaggcgc tggtcaacaa ggtccaggaa gtggtggtca acaaggacct 60
ggcggtcaag gaccctacgg tagtggccaa caaggtccag gtggagcagg acagcagggt 120
ccgggaggcc aaggacctta cggaccaggt gctgctgctg ccgccgctgc cgctgccgga 180
ggttacggtc caggagccgg acaacagggt ccaggtggag ctggacaaca aggtccagga 240
tcacaaggtc ctggtggaca aggtccatac ggtcctggtg ctggtcaaca gggaccaggt 300
agtcaaggac ctggttcagg tggtcagcag ggtccaggag gacagggtcc ttacggccct 360
tctgccgctg cagcagcagc cgctgccgca ggaggatacg gacctggtgc tggacaacga 420
tctcaaggac caggaggaca aggtccttat ggacctggcg ctggccaaca aggacctggt 480
tctcagggtc caggttcagg aggccaacaa ggcccaggag gtcaaggacc atacggacca 540
tccgctgcgg cagctgcagc tgctgcaggt ggatatggcc caggagccgg acaacagggt 600
cctggttcac aaggtccagg atctggtggt caacagggac caggcggcca gggaccttat 660
ggtccaggag ccgctgcagc agcagcagct gttggaggtt acggccctgg tgccggtcaa 720
caaggcccag gatctcaggg tcctggatct ggaggacaac aaggtcctgg aggtcagggt 780
ccatacggac cttcagcagc agctgctgct gcagccgctg gtggttatgg acctggtgct 840
ggtcaacaag gaccgggttc tcagggtccg ggttcaggag gtcagcaggg ccctggtgga 900
caaggacctt atggacctag tgcggctgca gcagctgccg ccgcaggtgg ttacggtcca 960
ggcgctggtc aacaaggtcc aggaagtggt ggtcaacaag gacctggcgg tcaaggaccc 1020
tacggtagtg gccaacaagg tccaggtgga gcaggacagc agggtccggg aggccaagga 1080
ccttacggac caggtgctgc tgctgccgcc gctgccgctg ccggaggtta cggtccagga 1140
gccggacaac agggtccagg tggagctgga caacaaggtc caggatcaca aggtcctggt 1200
ggacaaggtc catacggtcc tggtgctggt caacagggac caggtagtca aggacctggt 1260
tcaggtggtc agcagggtcc aggaggacag ggtccttacg gcccttctgc cgctgcagca 1320
gcagccgctg ccgcaggagg atacggacct ggtgctggac aacgatctca aggaccagga 1380
ggacaaggtc cttatggacc tggcgctggc caacaaggac ctggttctca gggtccaggt 1440
tcaggaggcc aacaaggccc aggaggtcaa ggaccatacg gaccatccgc tgcggcagct 1500
gcagctgctg caggtggata tggcccagga gccggacaac agggtcctgg ttcacaaggt 1560
ccaggatctg gtggtcaaca gggaccaggc ggccagggac cttatggtcc aggagccgct 1620
gcagcagcag cagctgttgg aggttacggc cctggtgccg gtcaacaagg cccaggatct 1680
cagggtcctg gatctggagg acaacaaggt cctggaggtc agggtccata cggaccttca 1740
gcagcagctg ctgctgcagc cgctggtggt tatggacctg gtgctggtca acaaggaccg 1800
ggttctcagg gtccgggttc aggaggtcag cagggccctg gtggacaagg accttatgga 1860
cctagtgcgg ctgcagcagc tgccgccgca ggtggttacg gtccaggcgc tggtcaacaa 1920
ggtccaggaa gtggtggtca acaaggacct ggcggtcaag gaccctacgg tagtggccaa 1980
caaggtccag gtggagcagg acagcagggt ccgggaggcc aaggacctta cggaccaggt 2040
gctgctgctg ccgccgctgc cgctgccgga ggttacggtc caggagccgg acaacagggt 2100
ccaggtggag ctggacaaca aggtccagga tcacaaggtc ctggtggaca aggtccatac 2160
ggtcctggtg ctggtcaaca gggaccaggt agtcaaggac ctggttcagg tggtcagcag 2220
ggtccaggag gacagggtcc ttacggccct tctgccgctg cagcagcagc cgctgccgca 2280
ggaggatacg gacctggtgc tggacaacga tctcaaggac caggaggaca aggtccttat 2340
ggacctggcg ctggccaaca aggacctggt tctcagggtc caggttcagg aggccaacaa 2400
ggcccaggag gtcaaggacc atacggacca tccgctgcgg cagctgcagc tgctgcaggt 2460
ggatatggcc caggagccgg acaacagggt cctggttcac aaggtccagg atctggtggt 2520
caacagggac caggcggcca gggaccttat ggtccaggag ccgctgcagc agcagcagct 2580
gttggaggtt acggccctgg tgccggtcaa caaggcccag gatctcaggg tcctggatct 2640
ggaggacaac aaggtcctgg aggtcagggt ccatacggac cttcagcagc agctgctgct 2700
gcagccgctg gtggttatgg acctggtgct ggtcaacaag gaccgggttc tcagggtccg 2760
ggttcaggag gtcagcaggg ccctggtgga caaggacctt atggacctag tgcggctgca 2820
gcagctgccg ccgca 2835
<210> 463
<211> 945
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polypeptide
<400> 463
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> 464
<211> 315
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polypeptide
<400> 464
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> 465
<211> 4324
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 465
ggagttgaat cacatcttac tggatagcga gctttttgac gaagtgaaaa tttctaattt 60
taaacaagag gaaggggtca aaaacggaga tatcttatac ttggaaaaag agatgacaat 120
cagtgatttc atcaattttg tatctagttg gccttctgtg ttttcgtgga agcagcaacg 180
aggaaaggag ggtatcctag atgattttta caacgaactg aacgactgct ttgagggggg 240
taacatgaaa gtaatatgga actccgtcct agtatttgcc aggaggaagc aaagggttgt 300
ataggcttta gtacttatag aggaaacggg gttacgtgca agcgcgcatg cctgagcttt 360
gagggggggg actttcacat ctcttcttct cacacttagc cctaacacag agaataataa 420
aaagcattgc aagatgagtg ttgtcagcaa gcaatacgac atccacgaag gcattatctt 480
tgtaattgaa ttgaccccgg agcttcacgc gccggcttca gaagggaaat ctcagctcca 540
gatcatctta gagaatgtca gtgaggttat ttctgagcta atcattacct tgcccggtac 600
aggaataggg tgttacctta ttaattacga cggtggtcaa aacgacgaaa tttaccccat 660
ttttgagtta caagacctga atttggaaat gatgaaacaa ttgtaccaag tcttggagga 720
ccatgtaagt gggcttaatc ctctcgagaa gcaattccca attgaacaca gtaaaccgtt 780
atcagccact ctgttctttc acttaaggtc tcttttttac atggcgaaga ctcataagcg 840
tactggaaga cattacaact tgaaaaagat tttcttgttc actaataacg ataaacctta 900
caatggaaac tctcagctga gagttccctt gaagaaaacc ctggctgatt acaatgacgt 960
agacattact ttgattccgt ttcttctgaa caagccttca ggtgtcaagt ttgacaagac 1020
ggaatactca gaaattttgt tctatgataa agatgcttgt tcgatgtcaa ttgaggagat 1080
ccgccaacga atttctagac ataaggagat caagcgggtt tacttcacct gtcctttgaa 1140
aatcgcaaat aacttgtgca tttctgtgaa aggttattct atgttttatc atgaaactcc 1200
aaggaagatc aaatttgtcg tcaatgaggg ttcaactttc aaagatgtgg agacaaaatc 1260
tcagtttgtc gatccaacat ccggaaaaga gttttccagt gaacagctga tcaaagcata 1320
tcctctaggt gccgatgctt acattccttt aaactcagag caagtcaaaa caataaatcg 1380
atttaatgat atcatcaata tcccctcttt ggaaattcta ggtttcaggg atatatctaa 1440
ttggttgcca cagtatcagt ttggcaaagc atcgttttta tcccctaata actatggtga 1500
ttttacacat tcgcagagaa catttagttg tcttcagtaa tgtcttgttt cttttgttgc 1560
agtggtgagc cattttgact tcgtgaaagt ttctttagaa tagttgtttc cagaggccaa 1620
acattccacc cgtagtaaag tgcaagcgta ggaagaccaa gactggcata aatcaggtat 1680
aagtgtcgag cactggcagg tgatcttctg aaagtttcta ctagcagata agatccagta 1740
gtcatgcata tggcaacaat gtaccgtgtg gatctaagaa cgcgtcctac taaccttcgc 1800
attcgttggt ccagtttgtt gttatcgatc aacgtgacaa ggttgtcgat tccgcgtaag 1860
catgcatacc caaggacgcc tgttgcaatt ccaagtgagc cagttccaac aatctttgta 1920
atattagagc acttcattgt gttgcgcttg aaagtaaaat gcgaacaaat taagagataa 1980
tctcgaaacc gcgacttcaa acgccaatat gatgtgcggc acacaataag cgttcatatc 2040
cgctgggtga ctttctcgct ttaaaaaatt atccgaaaaa atttttgacg gctagctcag 2100
tcctaggtac gctagcatta aagaggagaa aatggctaaa ctgacctctg ctgttccggt 2160
tctgaccgct cgtgacgttg ctggtgctgt tgagttctgg accgaccgtc tgggtttctc 2220
tcgtgacttc gttgaagacg acttcgctgg tgttgttcgt gacgacgtta ccctgttcat 2280
ctctgctgtt caggaccagg ttgttccgga caacaccctg gcttgggttt gggttcgtgg 2340
tctggacgaa ctgtacgctg aatggtctga agttgtttct accaacttcc gtgacgcttc 2400
tggtccggct atgaccgaaa tcggtgaaca gccgtggggt cgtgagttcg ctctgcgtga 2460
cccggctggt aactgcgttc acttcgttgc tgaagaacag gactaacacg tccgacggcg 2520
gcccacgggt cccaggcctc ggagatccgt cccccttttc ctttgtcgat atcatgtaat 2580
tagttatgtc acgcttacat tcacgccctc cccccacatc cgctctaacc gaaaaggaag 2640
gagttagaca acctgaagtc taggtcccta tttatttttt tatagttatg ttagtattaa 2700
gaacgttatt tatatttcaa atttttcttt tttttctgta cagacgcgtg tacgcatgta 2760
acattatact gaaaaccttg cttgagaagg ttttgggacg ctcgaaggct ttaatttgca 2820
agctgtatta gtttcacttt tcagcaacct ggtcggaaag atccacatca agaatggata 2880
ccaaccccaa gagtatgaaa atccttccct acaatggcac ttcaaaatgt tacgtgacga 2940
ttaccttcaa ttggaacacg atatcgacat cagtgacccc cttgagaaac aaaagtacat 3000
aaacagcctc gatgagacaa aaaccaagat catgaaacta cgggactatg tcaaggaaac 3060
tgccgatgat gacgaccctt cacggcttgc caacactctc aaagagctca accaagagct 3120
gaacaaaatt tccaactttg atatcatcgc caataagaag ccaaagaccc ccacgacagt 3180
agaccctgtt cctactgatg atgacatcat caacgcctgg aaggcaggaa ctctgaacgg 3240
tttcaaggtg gatcaattac gaaaatacgt aaggtcacga aacaactttc tggagacggc 3300
ctccaaaaag gcagatctca tcgccaacat tgacaagtac tttcagcaga agttcaaaga 3360
gactaaggcc tgattcgtgt tccttacttt ttcctcgcaa cgtgtttttt tcccaccaca 3420
ttgcctatgt tgtaatgcaa tgcagatgct ggcccagttt ttgacgattc tcgaaaattg 3480
gcattttcgt cgatgccatt ggccaaactg aaaattcaag acaaaataga ttggatttta 3540
tctgcaacgt cttccaccta cacaaccact ctacaaactt cagacaaaca tgtttataaa 3600
agcagctact agatccaaaa tgacaagttc gttattctct actacgtttg ttgtggcatt 3660
tggattggtg gctagcaaca acctcttgcc atgtcctgtt gaccactcta tgaataacga 3720
gactccgcaa gaattgaaac cattgcaggc tgaatcttct actagaaagt tgaactcttc 3780
cgcttaagtc aaataaaact actgacacag atgatgcaca gaaacaacgg atcacgctct 3840
tgactgatta gtcccgtcat tttggttctc attttcttca cagtcaccta tcaatgtatg 3900
atcacctgga aggatttccc tacgatactt caaatctttt acttgataat attactcatt 3960
atggctcagg aatgcagact gcctgattca agacgctgct cttcttattt aacacttgta 4020
cactaacccc atggaagcca gggaagggaa taaccatctc tctggtaata aatcggtctt 4080
tatttatgca tagaaaagga atctattata tttcgttcat ttggcactct gctaactgta 4140
gattaacggg tctcgtaaat tcaaaatctt cttccgatca aaccggggtg aaatattact 4200
tctcgtgcat agctaatttt caaataaccg tcctaaaatg aacggtcatt tacctggact 4260
ctcttgccaa atgggcaaca aaacataaag ctgatcagaa cgtaactagt ctctcggaat 4320
ccat 4324
<210> 466
<211> 22
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
oligonucleotide
<400> 466
ggagttgaat cacatcttac tg 22
<210> 467
<211> 1099
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 467
gacaactaaa tgttctctgc gaatgtgtaa aatcaccata gttattaggg gataaaaacg 60
atgctttgcc aaactgatac tgtggcaacc aattagatat atccctgaaa cctagaattt 120
ccaaagaggg gatattgatg atatcattaa atcgatttat tgttttgact tgctctgagt 180
ttaaaggaat gtaagcatcg gcacctagag gatatgcttt gatcagctgt tcactggaaa 240
actcttttcc ggatgttgga tcgacaaact gagattttgt ctccacatct ttgaaagttg 300
aaccctcatt gacgacaaat ttgatcttcc ttggagtttc atgataaaac atagaataac 360
ctttcacaga aatgcacaag ttatttgcga ttttcaaagg acaggtgaag taaacccgct 420
tgatctcctt atgtctagaa attcgttggc ggatctcctc aattgacatc gaacaagcat 480
ctttatcata gaacaaaatt tctgagtatt ccgtcttgtc aaacttgaca cctgaaggct 540
tgttcagaag aaacggaatc aaagtaatgt ctacgtcatt gtaatcagcc agggttttct 600
tcaagggaac tctcagctga gagtttccat tgtaaggttt atcgttatta gtgaacaaga 660
aaatcttttt caagttgtaa tgtcttccag tacgcttatg agtcttcgcc atgtaaaaaa 720
gagaccttaa gtgaaagaac agagtggctg ataacggttt actgtgttca attgggaatt 780
gcttctcgag aggattaagc ccacttacat ggtcctccaa gacttggtac aattgtttca 840
tcatttccaa attcaggtct tgtaactcaa aaatggggta aatttcgtcg ttttgaccac 900
cgtcgtaatt aataaggtaa caccctattc ctgtaccggg caaggtaatg attagctcag 960
aaataacctc actgacattc tctaagatga tctggagctg agatttccct tctgaagccg 1020
gcgcgtgaag ctccggggtc aattcaatta caaagataat gccttcgtgg atgtcgtatt 1080
gcttgctgac aacactcat 1099
<210> 468
<211> 549
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 468
tcaggcctta gtctctttga acttctgctg aaagtacttg tcaatgttgg cgatgagatc 60
tgcctttttg gaggccgtct ccagaaagtt gtttcgtgac cttacgtatt ttcgtaattg 120
atccaccttg aaaccgttca gagttcctgc cttccaggcg ttgatgatgt catcatcagt 180
aggaacaggg tctactgtcg tgggggtctt tggcttctta ttggcgatga tatcaaagtt 240
ggaaattttg ttcagctctt ggttgagctc tttgagagtg ttggcaagcc gtgaagggtc 300
gtcatcatcg gcagtttcct tgacatagtc ccgtagtttc atgatcttgg tttttgtctc 360
atcgaggctg tttatgtact tttgtttctc aagggggtca ctgatgtcga tatcgtgttc 420
caattgaagg taatcgtcac gtaacatttt gaagtgccat tgtagggaag gattttcata 480
ctcttggggt tggtatccat tcttgatgtg gatctttccg accaggttgc tgaaaagtga 540
aactaatac 549
<210> 469
<211> 552
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 469
ttcagtaatg tcttgtttct tttgttgcag tggtgagcca ttttgacttc gtgaaagttt 60
ctttagaata gttgtttcca gaggccaaac attccacccg tagtaaagtg caagcgtagg 120
aagaccaaga ctggcataaa tcaggtataa gtgtcgagca ctggcaggtg atcttctgaa 180
agtttctact agcagataag atccagtagt catgcatatg gcaacaatgt accgtgtgga 240
tctaagaacg cgtcctacta accttcgcat tcgttggtcc agtttgttgt tatcgatcaa 300
cgtgacaagg ttgtcgattc cgcgtaagca tgcataccca aggacgcctg ttgcaattcc 360
aagtgagcca gttccaacaa tctttgtaat attagagcac ttcattgtgt tgcgcttgaa 420
agtaaaatgc gaacaaatta agagataatc tcgaaaccgc gacttcaaac gccaatatga 480
tgtgcggcac acaataagcg ttcatatccg ctgggtgact ttctcgcttt aaaaaattat 540
ccgaaaaaat tt 552
<210> 470
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
oligonucleotide
<400> 470
cagaggccaa acattccacc 20
<210> 471
<211> 14
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
oligonucleotide
<400> 471
ttaaagagga gaaa 14
<210> 472
<211> 375
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 472
atggctaaac tgacctctgc tgttccggtt ctgaccgctc gtgacgttgc tggtgctgtt 60
gagttctgga ccgaccgtct gggtttctct cgtgacttcg ttgaagacga cttcgctggt 120
gttgttcgtg acgacgttac cctgttcatc tctgctgttc aggaccaggt tgttccggac 180
aacaccctgg cttgggtttg ggttcgtggt ctggacgaac tgtacgctga atggtctgaa 240
gttgtttcta ccaacttccg tgacgcttct ggtccggcta tgaccgaaat cggtgaacag 300
ccgtggggtc gtgagttcgc tctgcgtgac ccggctggta actgcgttca cttcgttgct 360
gaagaacagg actaa 375
<210> 473
<211> 318
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 473
cacgtccgac ggcggcccac gggtcccagg cctcggagat ccgtccccct tttcctttgt 60
cgatatcatg taattagtta tgtcacgctt acattcacgc cctcccccca catccgctct 120
aaccgaaaag gaaggagtta gacaacctga agtctaggtc cctatttatt tttttatagt 180
tatgttagta ttaagaacgt tatttatatt tcaaattttt cttttttttc tgtacagacg 240
cgtgtacgca tgtaacatta tactgaaaac cttgcttgag aaggttttgg gacgctcgaa 300
ggctttaatt tgcaagct 318
<210> 474
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
oligonucleotide
<400> 474
aggagttaga caacctgaag 20
<210> 475
<211> 23
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
oligonucleotide
<400> 475
gtaactagtc tctcggaatc cat 23
<210> 476
<211> 1623
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 476
cttcagagta cagaagatta agtgagagaa ttctaccgtt cgtatagcat acattatacg 60
aagttatttc agtaatgtct tgtttctttt gttgcagtgg tgagccattt tgacttcgtg 120
aaagtttctt tagaatagtt gtttccagag gccaaacatt ccacccgtag taaagtgcaa 180
gcgtaggaag accaagactg gcataaatca ggtataagtg tcgagcactg gcaggtgatc 240
ttctgaaagt ttctactagc agataagatc cagtagtcat gcatatggca acaatgtacc 300
gtgtggatct aagaacgcgt cctactaacc ttcgcattcg ttggtccagt ttgttgttat 360
cgatcaacgt gacaaggttg tcgattccgc gtaagcatgc atacccaagg acgcctgttg 420
caattccaag tgagccagtt ccaacaatct ttgtaatatt agagcacttc attgtgttgc 480
gcttgaaagt aaaatgcgaa caaattaaga gataatctcg aaaccgcgac ttcaaacgcc 540
aatatgatgt gcggcacaca ataagcgttc atatccgctg ggtgactttc tcgctttaaa 600
aaattatccg aaaaaatttt tgacggctag ctcagtccta ggtacgctag cattaaagag 660
gagaaaatga ctactcttga tgacacagcc tacagatata ggacatcagt tccgggtgac 720
gcagaggcta tcgaagcctt ggacggttca ttcactactg atacggtgtt tagagtcacc 780
gctacaggtg atggcttcac cttgagagag gttcctgtag acccaccctt aacgaaagtt 840
ttccctgatg acgaatcgga tgacgagtct gatgctggtg aggacggtga ccctgattcc 900
agaacatttg tcgcatacgg agatgatggt gacctggctg gctttgttgt ggtgtcctac 960
agcggatgga atcgtagact cacagttgag gacatcgaag ttgcacctga acatcgtggt 1020
cacggtgttg gtcgtgcact gatgggactg gcaacagagt ttgctagaga aagaggagcc 1080
ggacatttgt ggttagaagt gaccaatgtc aacgctcctg ctattcacgc atataggcga 1140
atgggtttca ctttgtgcgg tcttgatact gctttgtatg acggaactgc ttctgatggt 1200
gaacaagctc tttacatgag tatgccatgt ccatagcacg tccgacggcg gcccacgggt 1260
cccaggcctc ggagatccgt cccccttttc ctttgtcgat atcatgtaat tagttatgtc 1320
acgcttacat tcacgccctc cccccacatc cgctctaacc gaaaaggaag gagttagaca 1380
acctgaagtc taggtcccta tttatttttt tatagttatg ttagtattaa gaacgttatt 1440
tatatttcaa atttttcttt tttttctgta cagacgcgtg tacgcatgta acattatact 1500
gaaaaccttg cttgagaagg ttttgggacg ctcgaaggct ttaatttgca agctataact 1560
tcgtatagca tacattatac cttgttatgc ggccgcaaga agttgattga gactttcaac 1620
gag 1623
<210> 477
<211> 27
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
oligonucleotide
<400> 477
cttcagagta cagaagatta agtgaga 27
<210> 478
<211> 34
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
oligonucleotide
<400> 478
taccgttcgt atagcataca ttatacgaag ttat 34
<210> 479
<211> 552
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 479
ttcagtaatg tcttgtttct tttgttgcag tggtgagcca ttttgacttc gtgaaagttt 60
ctttagaata gttgtttcca gaggccaaac attccacccg tagtaaagtg caagcgtagg 120
aagaccaaga ctggcataaa tcaggtataa gtgtcgagca ctggcaggtg atcttctgaa 180
agtttctact agcagataag atccagtagt catgcatatg gcaacaatgt accgtgtgga 240
tctaagaacg cgtcctacta accttcgcat tcgttggtcc agtttgttgt tatcgatcaa 300
cgtgacaagg ttgtcgattc cgcgtaagca tgcataccca aggacgcctg ttgcaattcc 360
aagtgagcca gttccaacaa tctttgtaat attagagcac ttcattgtgt tgcgcttgaa 420
agtaaaatgc gaacaaatta agagataatc tcgaaaccgc gacttcaaac gccaatatga 480
tgtgcggcac acaataagcg ttcatatccg ctgggtgact ttctcgcttt aaaaaattat 540
ccgaaaaaat tt 552
<210> 480
<211> 14
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
oligonucleotide
<400> 480
ttaaagagga gaaa 14
<210> 481
<211> 570
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 481
atgactactc ttgatgacac agcctacaga tataggacat cagttccggg tgacgcagag 60
gctatcgaag ccttggacgg ttcattcact actgatacgg tgtttagagt caccgctaca 120
ggtgatggct tcaccttgag agaggttcct gtagacccac ccttaacgaa agttttccct 180
gatgacgaat cggatgacga gtctgatgct ggtgaggacg gtgaccctga ttccagaaca 240
tttgtcgcat acggagatga tggtgacctg gctggctttg ttgtggtgtc ctacagcgga 300
tggaatcgta gactcacagt tgaggacatc gaagttgcac ctgaacatcg tggtcacggt 360
gttggtcgtg cactgatggg actggcaaca gagtttgcta gagaaagagg agccggacat 420
ttgtggttag aagtgaccaa tgtcaacgct cctgctattc acgcatatag gcgaatgggt 480
ttcactttgt gcggtcttga tactgctttg tatgacggaa ctgcttctga tggtgaacaa 540
gctctttaca tgagtatgcc atgtccatag 570
<210> 482
<211> 318
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 482
cacgtccgac ggcggcccac gggtcccagg cctcggagat ccgtccccct tttcctttgt 60
cgatatcatg taattagtta tgtcacgctt acattcacgc cctcccccca catccgctct 120
aaccgaaaag gaaggagtta gacaacctga agtctaggtc cctatttatt tttttatagt 180
tatgttagta ttaagaacgt tatttatatt tcaaattttt cttttttttc tgtacagacg 240
cgtgtacgca tgtaacatta tactgaaaac cttgcttgag aaggttttgg gacgctcgaa 300
ggctttaatt tgcaagct 318
<210> 483
<211> 34
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
oligonucleotide
<400> 483
ataacttcgt atagcataca ttataccttg ttat 34
<210> 484
<211> 35
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
oligonucleotide
<400> 484
gcggccgcaa gaagttgatt gagactttca acgag 35
<210> 485
<211> 3869
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 485
tactacaggc tggctgttcc tcgcatggtg tttaatgtcc tgactgggtt ttcgtttatc 60
ggtattaccg gagccacctt gactgtaagg gaacgatact ggactaagag agtaatgcga 120
aaggcaacag cgtttctggc gaacctaatc aatgacggtt acgagtttac tactcctaaa 180
gccagtctta ttttgctaga gcgagtcaac gcttacttaa agggccaggg acctaattat 240
gacatcgatt ttgacgagca ggaggcgttc attaaagaaa tggaggagtt gaggacctct 300
ggtggatatg agaacagata ctcatattca ggaaccgatg aaacacccag agatccgggt 360
tgcctgtttc ttcccattgc tttaaataaa tggcactttg atgtgctaga ctgcctgagg 420
atatacggta ctcaggaaga tctggaatct aaattattaa gtgttcagca attggtgtta 480
caatgttgca tgaagcacag tggcatgact ccagacatgg tctttgcaac ggaagtagct 540
cagaagccga ccttcgaaga cgacatagtt tgtgatgata ttgacgctta tgcccagggg 600
ggtgattgtc tagattattg ttacacgcca agcaattact ccagaacttt agaaattcat 660
ggcaagattg ctaccttaca acgagagctg gggctatgct ataatattct cggaattttg 720
gaccgttttt ccgattaagg tttttagctc cattgcgcca acccccgctc tccagactcc 780
ttcgttatcc agcattcagc atggacaggt tcaaaaaata aaatttcttg atatgggtcc 840
acttcaaaca tgcgcctacc tgtaggaaaa aaaaagagaa cataaatatg ccgcgaacag 900
aaaacgtaat gtactgttct atatataaac tgttcagatc aatcataaat tctcagtttc 960
aaactttccg ctcagccaga ttttattcgt aaagaacgca tcattggctc tatgttgaag 1020
gatcagttct tgttatgggt tgctttgata gcgagcgtac cggtttccgg cgtgatggca 1080
gctcctagcg agtccgggca taacacggtt gaaaaacgag atgccaaaaa cgttgttggc 1140
gttcaacagt tggacttctt cagagtacag aagattaagt gagagaattc taccgttcgt 1200
atagcataca ttatacgaag ttatttcagt aatgtcttgt ttcttttgtt gcagtggtga 1260
gccattttga cttcgtgaaa gtttctttag aatagttgtt tccagaggcc aaacattcca 1320
cccgtagtaa agtgcaagcg taggaagacc aagactggca taaatcaggt ataagtgtcg 1380
agcactggca ggtgatcttc tgaaagtttc tactagcaga taagatccag tagtcatgca 1440
tatggcaaca atgtaccgtg tggatctaag aacgcgtcct actaaccttc gcattcgttg 1500
gtccagtttg ttgttatcga tcaacgtgac aaggttgtcg attccgcgta agcatgcata 1560
cccaaggacg cctgttgcaa ttccaagtga gccagttcca acaatctttg taatattaga 1620
gcacttcatt gtgttgcgct tgaaagtaaa atgcgaacaa attaagagat aatctcgaaa 1680
ccgcgacttc aaacgccaat atgatgtgcg gcacacaata agcgttcata tccgctgggt 1740
gactttctcg ctttaaaaaa ttatccgaaa aaatttttga cggctagctc agtcctaggt 1800
acgctagcat taaagaggag aaaatgacta ctcttgatga cacagcctac agatatagga 1860
catcagttcc gggtgacgca gaggctatcg aagccttgga cggttcattc actactgata 1920
cggtgtttag agtcaccgct acaggtgatg gcttcacctt gagagaggtt cctgtagacc 1980
cacccttaac gaaagttttc cctgatgacg aatcggatga cgagtctgat gctggtgagg 2040
acggtgaccc tgattccaga acatttgtcg catacggaga tgatggtgac ctggctggct 2100
ttgttgtggt gtcctacagc ggatggaatc gtagactcac agttgaggac atcgaagttg 2160
cacctgaaca tcgtggtcac ggtgttggtc gtgcactgat gggactggca acagagtttg 2220
ctagagaaag aggagccgga catttgtggt tagaagtgac caatgtcaac gctcctgcta 2280
ttcacgcata taggcgaatg ggtttcactt tgtgcggtct tgatactgct ttgtatgacg 2340
gaactgcttc tgatggtgaa caagctcttt acatgagtat gccatgtcca tagcacgtcc 2400
gacggcggcc cacgggtccc aggcctcgga gatccgtccc ccttttcctt tgtcgatatc 2460
atgtaattag ttatgtcacg cttacattca cgccctcccc ccacatccgc tctaaccgaa 2520
aaggaaggag ttagacaacc tgaagtctag gtccctattt atttttttat agttatgtta 2580
gtattaagaa cgttatttat atttcaaatt tttctttttt ttctgtacag acgcgtgtac 2640
gcatgtaaca ttatactgaa aaccttgctt gagaaggttt tgggacgctc gaaggcttta 2700
atttgcaagc tataacttcg tatagcatac attatacctt gttatgcggc cgcaagaagt 2760
tgattgagac tttcaacgag ggtccccttc agctaccttt ctctctgttt ggtagttatt 2820
ctcggcgtgt gtatagtata gtataaaagg gcctacattg gataggcttc aacattcctc 2880
aataaacaaa catccaacat cgcgcattcc gcatttcgca tttcacattt cgcgcctgcc 2940
ttcctttagg ttctttgaat catcatcaat cgtcgccgtc tacatcagag caggacttat 3000
ctttgccttc cccaaaaatt gccactccgt caaatagatt cttttgaatc cttgactatt 3060
tttgcctaaa taggtttttg ttagtttttc ttcaaagccc aaaagaaact ctatttagat 3120
tcatccagaa acaatctttt tctcacccca tttcgaagtg ccgtggagca cagacataaa 3180
aagatgacta ccgttcaacc tacagggcca gacaggctca ccctgccgca tattctactg 3240
gaattcaacg atggctcctc gcagcatgca gtgatcgagc taagcatgaa cgaggggatt 3300
aatatatcca cccatgagtg gaatccatcc actaatgagc aatcgccacg ggaagagaga 3360
gcaccacccc aacaatccaa tccatcgcat catccagaat catcgaacat agctactcaa 3420
agtcccgctc aggaaaccga gactcagccc ggcattccag gactagatag gcctgccttt 3480
gatacctcgg caacggggtc gtcagaacag gttgacccag tacagggaag gatcctggat 3540
gatattatag gccaatcatt aaggacttcc gaagaagacg ataccgaatc ccgccagaga 3600
ccacgagacc agaagaacat tatgatcacc gtgaattact tgtacgcaga cgacacaaat 3660
tccagaagtg ctaatacaaa caaccagacg cccaataaca cttctagaac ttccgacagt 3720
gaacgtgtgg gctccttatc gttgcacgtt ccggatctac cagataatgc cgacgattac 3780
tatatcgatg tactcattaa actaaccaca agcattgccc tcagcgtcat cacgtccatg 3840
atcaagaaac gattagggct tagcaggga 3869
<210> 486
<211> 1157
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 486
tactacaggc tggctgttcc tcgcatggtg tttaatgtcc tgactgggtt ttcgtttatc 60
ggtattaccg gagccacctt gactgtaagg gaacgatact ggactaagag agtaatgcga 120
aaggcaacag cgtttctggc gaacctaatc aatgacggtt acgagtttac tactcctaaa 180
gccagtctta ttttgctaga gcgagtcaac gcttacttaa agggccaggg acctaattat 240
gacatcgatt ttgacgagca ggaggcgttc attaaagaaa tggaggagtt gaggacctct 300
ggtggatatg agaacagata ctcatattca ggaaccgatg aaacacccag agatccgggt 360
tgcctgtttc ttcccattgc tttaaataaa tggcactttg atgtgctaga ctgcctgagg 420
atatacggta ctcaggaaga tctggaatct aaattattaa gtgttcagca attggtgtta 480
caatgttgca tgaagcacag tggcatgact ccagacatgg tctttgcaac ggaagtagct 540
cagaagccga ccttcgaaga cgacatagtt tgtgatgata ttgacgctta tgcccagggg 600
ggtgattgtc tagattattg ttacacgcca agcaattact ccagaacttt agaaattcat 660
ggcaagattg ctaccttaca acgagagctg gggctatgct ataatattct cggaattttg 720
gaccgttttt ccgattaagg tttttagctc cattgcgcca acccccgctc tccagactcc 780
ttcgttatcc agcattcagc atggacaggt tcaaaaaata aaatttcttg atatgggtcc 840
acttcaaaca tgcgcctacc tgtaggaaaa aaaaagagaa cataaatatg ccgcgaacag 900
aaaacgtaat gtactgttct atatataaac tgttcagatc aatcataaat tctcagtttc 960
aaactttccg ctcagccaga ttttattcgt aaagaacgca tcattggctc tatgttgaag 1020
gatcagttct tgttatgggt tgctttgata gcgagcgtac cggtttccgg cgtgatggca 1080
gctcctagcg agtccgggca taacacggtt gaaaaacgag atgccaaaaa cgttgttggc 1140
gttcaacagt tggactt 1157
<210> 487
<211> 1089
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 487
ggtccccttc agctaccttt ctctctgttt ggtagttatt ctcggcgtgt gtatagtata 60
gtataaaagg gcctacattg gataggcttc aacattcctc aataaacaaa catccaacat 120
cgcgcattcc gcatttcgca tttcacattt cgcgcctgcc ttcctttagg ttctttgaat 180
catcatcaat cgtcgccgtc tacatcagag caggacttat ctttgccttc cccaaaaatt 240
gccactccgt caaatagatt cttttgaatc cttgactatt tttgcctaaa taggtttttg 300
ttagtttttc ttcaaagccc aaaagaaact ctatttagat tcatccagaa acaatctttt 360
tctcacccca tttcgaagtg ccgtggagca cagacataaa aagatgacta ccgttcaacc 420
tacagggcca gacaggctca ccctgccgca tattctactg gaattcaacg atggctcctc 480
gcagcatgca gtgatcgagc taagcatgaa cgaggggatt aatatatcca cccatgagtg 540
gaatccatcc actaatgagc aatcgccacg ggaagagaga gcaccacccc aacaatccaa 600
tccatcgcat catccagaat catcgaacat agctactcaa agtcccgctc aggaaaccga 660
gactcagccc ggcattccag gactagatag gcctgccttt gatacctcgg caacggggtc 720
gtcagaacag gttgacccag tacagggaag gatcctggat gatattatag gccaatcatt 780
aaggacttcc gaagaagacg ataccgaatc ccgccagaga ccacgagacc agaagaacat 840
tatgatcacc gtgaattact tgtacgcaga cgacacaaat tccagaagtg ctaatacaaa 900
caaccagacg cccaataaca cttctagaac ttccgacagt gaacgtgtgg gctccttatc 960
gttgcacgtt ccggatctac cagataatgc cgacgattac tatatcgatg tactcattaa 1020
actaaccaca agcattgccc tcagcgtcat cacgtccatg atcaagaaac gattagggct 1080
tagcaggga 1089
<210> 488
<211> 3964
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 488
gccttctcgt gcaatcagag ctgttgaaag agagaagagg gcacacggaa gctgctgttc 60
aattgtgtga attgaccgga ttacaacctg ctggagtgat aggagagctg gttcgtgacg 120
aggacggctc tatgatgcga ttagacgact gtgttcagtt tggtctccgc cacaacgtaa 180
aaattatcaa ccttgaccag atcattgaat acatggattc caagaacagc tagatacgat 240
ggataggaat acagagatat catgattgag gaacgtaaga gctttttcga aagtgtgagt 300
ttgtggtgag ggccaggcgg tggggaggtg gtggggagcc tccttggtcg aatgtagata 360
tagtaagcaa gacacaagag cgcgcgaagt cttcaacgag gcggcgttgg gtcttgtacg 420
caacgtaatg actacacagt tgagcttgtc gcgaaccggt cgacattttg atcatgcata 480
ctatgttgag acaccatctc gtactattgc ggcaaccagc tgtaaatttg actaattaaa 540
gctgatgaag gatgcagggc gtcgtcaatt ttttgattga ttgcatttaa ttgtttgagc 600
cattcaaggc tgaatgcccg gcaccctaga cccttcttgt gagtactata aacccgcagg 660
cagggtaccc ttggccttct gcgagactac cagtcataac gtatatccac aatgtactag 720
taatagcccc ggaaaactct aatcccacag aacgtctaac gcctcctatg tcatcgatac 780
ccattcgcac tactgccatg gcccccctta cgtgatcatt tcacttactc ccgcctaagc 840
ttcgcccaca tgcctgcgtt ttgccaagat ttactgacga gtttggttta ctcatcctct 900
atttataact actagacttt caccattctt caccaccctc gtgccaatga tcatcaacca 960
cttggtattg acagccctca gcattgcact agcaagtgcg caactccaat cgcctttcac 1020
ttcagagtac agaagattaa gtgagagaat tctaccgttc gtatagcata cattatacga 1080
agttatttca gtaatgtctt gtttcttttg ttgcagtggt gagccatttt gacttcgtga 1140
aagtttcttt agaatagttg tttccagagg ccaaacattc cacccgtagt aaagtgcaag 1200
cgtaggaaga ccaagactgg cataaatcag gtataagtgt cgagcactgg caggtgatct 1260
tctgaaagtt tctactagca gataagatcc agtagtcatg catatggcaa caatgtaccg 1320
tgtggatcta agaacgcgtc ctactaacct tcgcattcgt tggtccagtt tgttgttatc 1380
gatcaacgtg acaaggttgt cgattccgcg taagcatgca tacccaagga cgcctgttgc 1440
aattccaagt gagccagttc caacaatctt tgtaatatta gagcacttca ttgtgttgcg 1500
cttgaaagta aaatgcgaac aaattaagag ataatctcga aaccgcgact tcaaacgcca 1560
atatgatgtg cggcacacaa taagcgttca tatccgctgg gtgactttct cgctttaaaa 1620
aattatccga aaaaattttt gacggctagc tcagtcctag gtacgctagc attaaagagg 1680
agaaaatgac tactcttgat gacacagcct acagatatag gacatcagtt ccgggtgacg 1740
cagaggctat cgaagccttg gacggttcat tcactactga tacggtgttt agagtcaccg 1800
ctacaggtga tggcttcacc ttgagagagg ttcctgtaga cccaccctta acgaaagttt 1860
tccctgatga cgaatcggat gacgagtctg atgctggtga ggacggtgac cctgattcca 1920
gaacatttgt cgcatacgga gatgatggtg acctggctgg ctttgttgtg gtgtcctaca 1980
gcggatggaa tcgtagactc acagttgagg acatcgaagt tgcacctgaa catcgtggtc 2040
acggtgttgg tcgtgcactg atgggactgg caacagagtt tgctagagaa agaggagccg 2100
gacatttgtg gttagaagtg accaatgtca acgctcctgc tattcacgca tataggcgaa 2160
tgggtttcac tttgtgcggt cttgatactg ctttgtatga cggaactgct tctgatggtg 2220
aacaagctct ttacatgagt atgccatgtc catagcacgt ccgacggcgg cccacgggtc 2280
ccaggcctcg gagatccgtc ccccttttcc tttgtcgata tcatgtaatt agttatgtca 2340
cgcttacatt cacgccctcc ccccacatcc gctctaaccg aaaaggaagg agttagacaa 2400
cctgaagtct aggtccctat ttattttttt atagttatgt tagtattaag aacgttattt 2460
atatttcaaa tttttctttt ttttctgtac agacgcgtgt acgcatgtaa cattatactg 2520
aaaaccttgc ttgagaaggt tttgggacgc tcgaaggctt taatttgcaa gctataactt 2580
cgtatagcat acattatacc ttgttatgcg gccgcaagaa gttgattgag actttcaacg 2640
agctggctct gcttctggta cttcttcagg tgcatcttct gctactcaaa atgacgaaac 2700
atccactgat cttggagctc cagctgcatc tttaagtgca acgccatgtc tttttgccat 2760
cttgctgctc atgttgtagt agactttttt tttcactgag tttttatgta ctactgatta 2820
cattgtgtag gtgtaatgat gtgcactata atactaatat agtcaaaatg ctacagagga 2880
aagtgcaggt tgcctgtggt ggtttttctt attagcaccc tctgaacact ctttacctct 2940
aacatcctca gccatgctaa tcgcgcataa aataaatctt cgaacttttt tccattttat 3000
gctcataaag cttccttact gtcaccttat caaaagagct tttgccacta aagtagtcac 3060
acccagaatt gctcccgaat atcgtccaac aatgctagga tctgtggaaa gtttgacaaa 3120
taatttgaac accttgagct tgaagcttcc tgaagttaat atccaaggct cctttccaga 3180
aagtaaccca gtggaccttt tgagaaacta catcactcaa gaacttagta aaatttctgg 3240
agttgacaaa gaattgattt tcccagcctt ggaatggggt accacactgg aaaaaggtga 3300
tcttttgatc ccagttcctc gtctgagaat aaagggtgct aatcctaaag atttagccga 3360
acaatgggct gctgcattcc caaagggtgg atatcttaaa gacgttattg cgcaaggacc 3420
tttcttgcag ttctttttta acacatcggt tctgtacaag ttggtgatat ctgatgctct 3480
ggagagaggc gatgactttg gtgcacttcc tctaggaaag ggacaaaaag ttatagtgga 3540
gttttcttct ccaaatattg ccaaaccttt ccacgctggc catcttagaa gtacaatcat 3600
cggtggtttt atttccaatc tgtatgaaaa gctgggtcat gaagttatga ggatgaatta 3660
tttgggagac tggggaaaac aatttggtgt tcttgcagta ggatttgagc gttacggtga 3720
tgaggcaaaa ttaaagactg atccaatcaa ccatttgttt gaggtctatg ttaaaatcaa 3780
ccaagatatt aaggctcaat cagagtctac tgaggagatt gcagaagggc aatcattaga 3840
tgaccaggca agagcttttt tcaagaaaat ggaaaatggc gacgaatcgg ctgtaagctt 3900
gtggaaaaga ttccgtgagt tatccattga gaagtacatt gatacttatg cccgcctcaa 3960
catc 3964
<210> 489
<211> 1019
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 489
gccttctcgt gcaatcagag ctgttgaaag agagaagagg gcacacggaa gctgctgttc 60
aattgtgtga attgaccgga ttacaacctg ctggagtgat aggagagctg gttcgtgacg 120
aggacggctc tatgatgcga ttagacgact gtgttcagtt tggtctccgc cacaacgtaa 180
aaattatcaa ccttgaccag atcattgaat acatggattc caagaacagc tagatacgat 240
ggataggaat acagagatat catgattgag gaacgtaaga gctttttcga aagtgtgagt 300
ttgtggtgag ggccaggcgg tggggaggtg gtggggagcc tccttggtcg aatgtagata 360
tagtaagcaa gacacaagag cgcgcgaagt cttcaacgag gcggcgttgg gtcttgtacg 420
caacgtaatg actacacagt tgagcttgtc gcgaaccggt cgacattttg atcatgcata 480
ctatgttgag acaccatctc gtactattgc ggcaaccagc tgtaaatttg actaattaaa 540
gctgatgaag gatgcagggc gtcgtcaatt ttttgattga ttgcatttaa ttgtttgagc 600
cattcaaggc tgaatgcccg gcaccctaga cccttcttgt gagtactata aacccgcagg 660
cagggtaccc ttggccttct gcgagactac cagtcataac gtatatccac aatgtactag 720
taatagcccc ggaaaactct aatcccacag aacgtctaac gcctcctatg tcatcgatac 780
ccattcgcac tactgccatg gcccccctta cgtgatcatt tcacttactc ccgcctaagc 840
ttcgcccaca tgcctgcgtt ttgccaagat ttactgacga gtttggttta ctcatcctct 900
atttataact actagacttt caccattctt caccaccctc gtgccaatga tcatcaacca 960
cttggtattg acagccctca gcattgcact agcaagtgcg caactccaat cgcctttca 1019
<210> 490
<211> 1322
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 490
ctggctctgc ttctggtact tcttcaggtg catcttctgc tactcaaaat gacgaaacat 60
ccactgatct tggagctcca gctgcatctt taagtgcaac gccatgtctt tttgccatct 120
tgctgctcat gttgtagtag actttttttt tcactgagtt tttatgtact actgattaca 180
ttgtgtaggt gtaatgatgt gcactataat actaatatag tcaaaatgct acagaggaaa 240
gtgcaggttg cctgtggtgg tttttcttat tagcaccctc tgaacactct ttacctctaa 300
catcctcagc catgctaatc gcgcataaaa taaatcttcg aacttttttc cattttatgc 360
tcataaagct tccttactgt caccttatca aaagagcttt tgccactaaa gtagtcacac 420
ccagaattgc tcccgaatat cgtccaacaa tgctaggatc tgtggaaagt ttgacaaata 480
atttgaacac cttgagcttg aagcttcctg aagttaatat ccaaggctcc tttccagaaa 540
gtaacccagt ggaccttttg agaaactaca tcactcaaga acttagtaaa atttctggag 600
ttgacaaaga attgattttc ccagccttgg aatggggtac cacactggaa aaaggtgatc 660
ttttgatccc agttcctcgt ctgagaataa agggtgctaa tcctaaagat ttagccgaac 720
aatgggctgc tgcattccca aagggtggat atcttaaaga cgttattgcg caaggacctt 780
tcttgcagtt cttttttaac acatcggttc tgtacaagtt ggtgatatct gatgctctgg 840
agagaggcga tgactttggt gcacttcctc taggaaaggg acaaaaagtt atagtggagt 900
tttcttctcc aaatattgcc aaacctttcc acgctggcca tcttagaagt acaatcatcg 960
gtggttttat ttccaatctg tatgaaaagc tgggtcatga agttatgagg atgaattatt 1020
tgggagactg gggaaaacaa tttggtgttc ttgcagtagg atttgagcgt tacggtgatg 1080
aggcaaaatt aaagactgat ccaatcaacc atttgtttga ggtctatgtt aaaatcaacc 1140
aagatattaa ggctcaatca gagtctactg aggagattgc agaagggcaa tcattagatg 1200
accaggcaag agcttttttc aagaaaatgg aaaatggcga cgaatcggct gtaagcttgt 1260
ggaaaagatt ccgtgagtta tccattgaga agtacattga tacttatgcc cgcctcaaca 1320
tc 1322
<210> 491
<211> 3932
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 491
gacgagacgc tgttcctttc aacttgtcca cttggactga caagtcaaca cctgttacta 60
attcttttgt catctctcag tatgaagaca cgcgtgttcc tcaatcagcc accagttcta 120
cacatccaaa catacctaaa cacgccaaag agtatccgtt agcaaatggg ccacctgggt 180
ggtgttggaa ttcccattcc agtatgtcga cagaccaacc aatatatcca ggacaccaat 240
atccaccacc gcttcagcag cactaccact ttgcttcacc caggcaacta tcaaactcta 300
gctctgggac gtcatccgtt cctttccaac caccccctgc tggtcaatta caaccacaag 360
gtaattctat gttcatacac atgccatttt cgctaaatgg cccaccagct gctggacagc 420
aattgatacc accccaagga ctagcctcaa tacctgtcgg ccccggcaac aacagttccc 480
tattggttag ccaaggtgca cctggcggct attctttagc ttcaccagcg ttgtcaccgg 540
tagatgcgac cttcgaagat cccgtcaaga gactgcccaa aaagcggaca aaaactggat 600
gtctcacttg ccgtaagaga cgaatcaaat gtgacgaacg caagccgttc tgtttcaact 660
gtgaaaaaag caaaaaggtg tgtactggtt ttacgcatct attcaaagat ccccctagca 720
aatcctaccc tcccagttca gatggtgcct cccctgttgc caatgaccac cctgtccccc 780
caaggcaaaa ctttggtgaa ttgaggggca gtctgaatta catcatcaac tagaagaatg 840
cttattcctt ttctctactg tataatcacg acgttatgtc ctttaatata agaaacgaca 900
attaaaccac tttaggtgga cataatccat ttctggatgc tgttcgatgt gtagtgtcta 960
aaccgatact gagatttctc tttctctttc tctttttttt ttttttccta ccatttcctt 1020
caagaaaata cacctttcga cagatcatca taaatggtgg cctctcttca cacttcagag 1080
tacagaagat taagtgagag aattctaccg ttcgtatagc atacattata cgaagttatt 1140
tcagtaatgt cttgtttctt ttgttgcagt ggtgagccat tttgacttcg tgaaagtttc 1200
tttagaatag ttgtttccag aggccaaaca ttccacccgt agtaaagtgc aagcgtagga 1260
agaccaagac tggcataaat caggtataag tgtcgagcac tggcaggtga tcttctgaaa 1320
gtttctacta gcagataaga tccagtagtc atgcatatgg caacaatgta ccgtgtggat 1380
ctaagaacgc gtcctactaa ccttcgcatt cgttggtcca gtttgttgtt atcgatcaac 1440
gtgacaaggt tgtcgattcc gcgtaagcat gcatacccaa ggacgcctgt tgcaattcca 1500
agtgagccag ttccaacaat ctttgtaata ttagagcact tcattgtgtt gcgcttgaaa 1560
gtaaaatgcg aacaaattaa gagataatct cgaaaccgcg acttcaaacg ccaatatgat 1620
gtgcggcaca caataagcgt tcatatccgc tgggtgactt tctcgcttta aaaaattatc 1680
cgaaaaaatt tttgacggct agctcagtcc taggtacgct agcattaaag aggagaaaat 1740
gactactctt gatgacacag cctacagata taggacatca gttccgggtg acgcagaggc 1800
tatcgaagcc ttggacggtt cattcactac tgatacggtg tttagagtca ccgctacagg 1860
tgatggcttc accttgagag aggttcctgt agacccaccc ttaacgaaag ttttccctga 1920
tgacgaatcg gatgacgagt ctgatgctgg tgaggacggt gaccctgatt ccagaacatt 1980
tgtcgcatac ggagatgatg gtgacctggc tggctttgtt gtggtgtcct acagcggatg 2040
gaatcgtaga ctcacagttg aggacatcga agttgcacct gaacatcgtg gtcacggtgt 2100
tggtcgtgca ctgatgggac tggcaacaga gtttgctaga gaaagaggag ccggacattt 2160
gtggttagaa gtgaccaatg tcaacgctcc tgctattcac gcatataggc gaatgggttt 2220
cactttgtgc ggtcttgata ctgctttgta tgacggaact gcttctgatg gtgaacaagc 2280
tctttacatg agtatgccat gtccatagca cgtccgacgg cggcccacgg gtcccaggcc 2340
tcggagatcc gtcccccttt tcctttgtcg atatcatgta attagttatg tcacgcttac 2400
attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga caacctgaag 2460
tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta tttatatttc 2520
aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata ctgaaaacct 2580
tgcttgagaa ggttttggga cgctcgaagg ctttaatttg caagctataa cttcgtatag 2640
catacattat accttgttat gcggccgcaa gaagttgatt gagactttca acgagtgatc 2700
gactacttgg cctccgccgt gaaaactcaa ttagatgtta gctccaaatt aatgaacctg 2760
gtacaagatg ataaatagga actcaaatac aaagcctacc attaatgact gttttatttt 2820
tatactaaag tagctaaagg gtgattatca aggagtggtt aacgatctat tcctagcagg 2880
gcactcagct catcgatctt tccaatatcg gcgtataacg cttccacttc tatcaacgta 2940
tcttcgttaa aaagaccacc tctggtggga actaatcctt ctgctgccgc ctctgctaaa 3000
ctctgtcttc gaatccgttt cttactaaca tcagcttcga cagataagcc actcttcttt 3060
atctttttct tagatcctgt tttgaatctc agggacttta ctggtgccat aacaacttcc 3120
tgttccagta ccttgttctt cttactcttt tttggtatta aagaatgtcc cgccttgagt 3180
cctcgatcat ccttggccat actcaatcgt ctagtagtgc tgttgaaatg ctgtaaagaa 3240
gaggaatatc ttcttaaatg gttggtatct ttttcagcaa ccacaccttt gtttcggaaa 3300
gcggataatg gcacattgct tggattgata gaagaagcta taaaagccca tcctgcgttt 3360
ggagcagttt gattgctctg agttactatg ttcaactgtg tattggcaaa agccttagag 3420
tcgctgtctg attcgcttat attgagtaaa tcatccaggt ccaatagagg aacagaacca 3480
gtctgcttcc cttttggttt tgtacgatcc ctaattgcac ccttcacaga aagttctacc 3540
cgtttggact ttatactgtc tttgttctct gatactgatc gcattgaaaa cccatcaata 3600
atctcaaagg gtttgccaca gtccgaggtg gtccaaattc caatcactgg agggatagga 3660
tccactttgg aagatgccag aacttctttt gcaattttgg taccaatttt tttattggat 3720
gttttgggaa gagcttcatc ttcatcagtg gagttgctgc tttcgttgtc atctactttt 3780
tggtcatctt ctagttcgtc gtcgtctgaa gcaatagcat ctgaggagga cgcatctcct 3840
tcacctttga aaaagtaatt aaataggtag gagtcatcat cagaatcttg ttcttggtct 3900
gatccccttt cgacggcagc ttgaatgttg tt 3932
<210> 492
<211> 1072
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 492
gacgagacgc tgttcctttc aacttgtcca cttggactga caagtcaaca cctgttacta 60
attcttttgt catctctcag tatgaagaca cgcgtgttcc tcaatcagcc accagttcta 120
cacatccaaa catacctaaa cacgccaaag agtatccgtt agcaaatggg ccacctgggt 180
ggtgttggaa ttcccattcc agtatgtcga cagaccaacc aatatatcca ggacaccaat 240
atccaccacc gcttcagcag cactaccact ttgcttcacc caggcaacta tcaaactcta 300
gctctgggac gtcatccgtt cctttccaac caccccctgc tggtcaatta caaccacaag 360
gtaattctat gttcatacac atgccatttt cgctaaatgg cccaccagct gctggacagc 420
aattgatacc accccaagga ctagcctcaa tacctgtcgg ccccggcaac aacagttccc 480
tattggttag ccaaggtgca cctggcggct attctttagc ttcaccagcg ttgtcaccgg 540
tagatgcgac cttcgaagat cccgtcaaga gactgcccaa aaagcggaca aaaactggat 600
gtctcacttg ccgtaagaga cgaatcaaat gtgacgaacg caagccgttc tgtttcaact 660
gtgaaaaaag caaaaaggtg tgtactggtt ttacgcatct attcaaagat ccccctagca 720
aatcctaccc tcccagttca gatggtgcct cccctgttgc caatgaccac cctgtccccc 780
caaggcaaaa ctttggtgaa ttgaggggca gtctgaatta catcatcaac tagaagaatg 840
cttattcctt ttctctactg tataatcacg acgttatgtc ctttaatata agaaacgaca 900
attaaaccac tttaggtgga cataatccat ttctggatgc tgttcgatgt gtagtgtcta 960
aaccgatact gagatttctc tttctctttc tctttttttt ttttttccta ccatttcctt 1020
caagaaaata cacctttcga cagatcatca taaatggtgg cctctcttca ca 1072
<210> 493
<211> 1237
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 493
tgatcgacta cttggcctcc gccgtgaaaa ctcaattaga tgttagctcc aaattaatga 60
acctggtaca agatgataaa taggaactca aatacaaagc ctaccattaa tgactgtttt 120
atttttatac taaagtagct aaagggtgat tatcaaggag tggttaacga tctattccta 180
gcagggcact cagctcatcg atctttccaa tatcggcgta taacgcttcc acttctatca 240
acgtatcttc gttaaaaaga ccacctctgg tgggaactaa tccttctgct gccgcctctg 300
ctaaactctg tcttcgaatc cgtttcttac taacatcagc ttcgacagat aagccactct 360
tctttatctt tttcttagat cctgttttga atctcaggga ctttactggt gccataacaa 420
cttcctgttc cagtaccttg ttcttcttac tcttttttgg tattaaagaa tgtcccgcct 480
tgagtcctcg atcatccttg gccatactca atcgtctagt agtgctgttg aaatgctgta 540
aagaagagga atatcttctt aaatggttgg tatctttttc agcaaccaca cctttgtttc 600
ggaaagcgga taatggcaca ttgcttggat tgatagaaga agctataaaa gcccatcctg 660
cgtttggagc agtttgattg ctctgagtta ctatgttcaa ctgtgtattg gcaaaagcct 720
tagagtcgct gtctgattcg cttatattga gtaaatcatc caggtccaat agaggaacag 780
aaccagtctg cttccctttt ggttttgtac gatccctaat tgcacccttc acagaaagtt 840
ctacccgttt ggactttata ctgtctttgt tctctgatac tgatcgcatt gaaaacccat 900
caataatctc aaagggtttg ccacagtccg aggtggtcca aattccaatc actggaggga 960
taggatccac tttggaagat gccagaactt cttttgcaat tttggtacca atttttttat 1020
tggatgtttt gggaagagct tcatcttcat cagtggagtt gctgctttcg ttgtcatcta 1080
ctttttggtc atcttctagt tcgtcgtcgt ctgaagcaat agcatctgag gaggacgcat 1140
ctccttcacc tttgaaaaag taattaaata ggtaggagtc atcatcagaa tcttgttctt 1200
ggtctgatcc cctttcgacg gcagcttgaa tgttgtt 1237
<210> 494
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 494
Ser Gly Ala Gly Gly
1 5
<210> 495
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 495
Gly Ser Gly Ala Gly
1 5
<210> 496
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 496
Gly Gly Ser Gly Ala
1 5
<210> 497
<211> 181
<212> PRT
<213> Aliatypus gulosus
<400> 497
Gly Ala Ala Ser Ser Ser Ser Thr Ile Ile Thr Thr Lys Ser Ala Ser
1 5 10 15
Ala Ser Ala Ala Ala Asp Ala Ser Ala Ala Ala Thr Ala Ser Ala Ala
20 25 30
Ser Arg Ser Ser Ala Asn Ala Ala Ala Ser Ala Phe Ala Gln Ser Phe
35 40 45
Ser Ser Ile Leu Leu Glu Ser Gly Tyr Phe Cys Ser Ile Phe Gly Ser
50 55 60
Ser Ile Ser Ser Ser Tyr Ala Ala Ala Ile Ala Ser Ala Ala Ser Arg
65 70 75 80
Ala Ala Ala Glu Ser Asn Gly Tyr Thr Thr His Ala Tyr Ala Cys Ala
85 90 95
Lys Ala Val Ala Ser Ala Val Glu Arg Val Thr Ser Gly Ala Asp Ala
100 105 110
Tyr Ala Tyr Ala Gln Ala Ile Ser Asp Ala Leu Ser His Ala Leu Leu
115 120 125
Tyr Thr Gly Arg Leu Asn Thr Ala Asn Ala Asn Ser Leu Ala Ser Ala
130 135 140
Phe Ala Tyr Ala Phe Ala Asn Ala Ala Ala Gln Ala Ser Ala Ser Ser
145 150 155 160
Ala Ser Ala Gly Ala Ala Ser Ala Ser Gly Ala Ala Ser Ala Ser Gly
165 170 175
Ala Gly Ser Ala Ser
180
<210> 498
<211> 126
<212> PRT
<213> Plectreurys tristis
<400> 498
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
115 120 125
<210> 499
<211> 239
<212> PRT
<213> Plectreurys tristis
<400> 499
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> 500
<211> 182
<212> PRT
<213> Araneus gemmoides
<400> 500
Gly Asn Val Gly Tyr Gln Leu Gly Leu Lys Val Ala Asn Ser Leu Gly
1 5 10 15
Leu Gly Asn Ala Gln Ala Leu Ala Ser Ser Leu Ser Gln Ala Val Ser
20 25 30
Ala Val Gly Val Gly Ala Ser Ser Asn Ala Tyr Ala Asn Ala Val Ser
35 40 45
Asn Ala Val Gly Gln Val Leu Ala Gly Gln Gly Ile Leu Asn Ala Ala
50 55 60
Asn Ala Gly Ser Leu Ala Ser Ser Phe Ala Ser Ala Leu Ser Ser Ser
65 70 75 80
Ala Ala Ser Val Ala Ser Gln Ser Ala Ser Gln Ser Gln Ala Ala Ser
85 90 95
Gln Ser Gln Ala Ala Ala Ser Ala Phe Arg Gln Ala Ala Ser Gln Ser
100 105 110
Ala Ser Gln Ser Asp Ser Arg Ala Gly Ser Gln Ser Ser Thr Lys Thr
115 120 125
Thr Ser Thr Ser Thr Ser Gly Ser Gln Ala Asp Ser Arg Ser Ala Ser
130 135 140
Ser Ser Ala Ser Gln Ala Ser Ala Ser Ala Phe Ala Gln Gln Ser Ser
145 150 155 160
Ala Ser Leu Ser Ser Ser Ser Ser Phe Ser Ser Ala Phe Ser Ser Ala
165 170 175
Thr Ser Ile Ser Ala Val
180
<210> 501
<211> 180
<212> PRT
<213> Argiope aurantia
<400> 501
Gly Ser Leu Ala Ser Ser Phe Ala Ser Ala Leu Ser Ala Ser Ala Ala
1 5 10 15
Ser Val Ala Ser Ser Ala Ala Ala Gln Ala Ala Ser Gln Ser Gln Ala
20 25 30
Ala Ala Ser Ala Phe Ser Arg Ala Ala Ser Gln Ser Ala Ser Gln Ser
35 40 45
Ala Ala Arg Ser Gly Ala Gln Ser Ile Ser Thr Thr Thr Thr Thr Ser
50 55 60
Thr Ala Gly Ser Gln Ala Ala Ser Gln Ser Ala Ser Ser Ala Ala Ser
65 70 75 80
Gln Ala Ser Ala Ser Ser Phe Ala Arg Ala Ser Ser Ala Ser Leu Ala
85 90 95
Ala Ser Ser Ser Phe Ser Ser Ala Phe Ser Ser Ala Asn Ser Leu Ser
100 105 110
Ala Leu Gly Asn Val Gly Tyr Gln Leu Gly Phe Asn Val Ala Asn Asn
115 120 125
Leu Gly Ile Gly Asn Ala Ala Gly Leu Gly Asn Ala Leu Ser Gln Ala
130 135 140
Val Ser Ser Val Gly Val Gly Ala Ser Ser Ser Thr Tyr Ala Asn Ala
145 150 155 160
Val Ser Asn Ala Val Gly Gln Phe Leu Ala Gly Gln Gly Ile Leu Asn
165 170 175
Ala Ala Asn Ala
180
<210> 502
<211> 199
<212> PRT
<213> Deinopis spinosa
<400> 502
Gly Ala Ser Ala Ser Ala Tyr Ala Ser Ala Ile Ser Asn Ala Val Gly
1 5 10 15
Pro Tyr Leu Tyr Gly Leu Gly Leu Phe Asn Gln Ala Asn Ala Ala Ser
20 25 30
Phe Ala Ser Ser Phe Ala Ser Ala Val Ser Ser Ala Val Ala Ser Ala
35 40 45
Ser Ala Ser Ala Ala Ser Ser Ala Tyr Ala Gln Ser Ala Ala Ala Gln
50 55 60
Ala Gln Ala Ala Ser Ser Ala Phe Ser Gln Ala Ala Ala Gln Ser Ala
65 70 75 80
Ala Ala Ala Ser Ala Gly Ala Ser Ala Gly Ala Gly Ala Ser Ala Gly
85 90 95
Ala Gly Ala Val Ala Gly Ala Gly Ala Val Ala Gly Ala Gly Ala Val
100 105 110
Ala Gly Ala Ser Ala Ala Ala Ala Ser Gln Ala Ala Ala Ser Ser Ser
115 120 125
Ala Ser Ala Val Ala Ser Ala Phe Ala Gln Ser Ala Ser Tyr Ala Leu
130 135 140
Ala Ser Ser Ser Ala Phe Ala Asn Ala Phe Ala Ser Ala Thr Ser Ala
145 150 155 160
Gly Tyr Leu Gly Ser Leu Ala Tyr Gln Leu Gly Leu Thr Thr Ala Tyr
165 170 175
Asn Leu Gly Leu Ser Asn Ala Gln Ala Phe Ala Ser Thr Leu Ser Gln
180 185 190
Ala Val Thr Gly Val Gly Leu
195
<210> 503
<211> 171
<212> PRT
<213> Nephila clavipes
<400> 503
Gly Ala Thr Ala Ala Ser Tyr Gly Asn Ala Leu Ser Thr Ala Ala Ala
1 5 10 15
Gln Phe Phe Ala Thr Ala Gly Leu Leu Asn Ala Gly Asn Ala Ser Ala
20 25 30
Leu Ala Ser Ser Phe Ala Arg Ala Phe Ser Ala Ser Ala Glu Ser Gln
35 40 45
Ser Phe Ala Gln Ser Gln Ala Phe Gln Gln Ala Ser Ala Phe Gln Gln
50 55 60
Ala Ala Ser Arg Ser Ala Ser Gln Ser Ala Ala Glu Ala Gly Ser Thr
65 70 75 80
Ser Ser Ser Thr Thr Thr Thr Thr Ser Ala Ala Arg Ser Gln Ala Ala
85 90 95
Ser Gln Ser Ala Ser Ser Ser Tyr Ser Ser Ala Phe Ala Gln Ala Ala
100 105 110
Ser Ser Ser Leu Ala Thr Ser Ser Ala Leu Ser Arg Ala Phe Ser Ser
115 120 125
Val Ser Ser Ala Ser Ala Ala Ser Ser Leu Ala Tyr Ser Ile Gly Leu
130 135 140
Ser Ala Ala Arg Ser Leu Gly Ile Ala Asp Ala Ala Gly Leu Ala Gly
145 150 155 160
Val Leu Ala Arg Ala Ala Gly Ala Leu Gly Gln
165 170
<210> 504
<211> 268
<212> PRT
<213> Argiope trifasciata
<400> 504
Gly Gly Ala Pro Gly Gly Gly Pro Gly Gly Ala Gly Pro Gly Gly Ala
1 5 10 15
Gly Phe Gly Pro Gly Gly Gly Ala Gly Phe Gly Pro Gly Gly Gly Ala
20 25 30
Gly Phe Gly Pro Gly Gly Ala Ala Gly Gly Pro Gly Gly Pro Gly Gly
35 40 45
Pro Gly Gly Pro Gly Gly Ala Gly Gly Tyr Gly Pro Gly Gly Ala Gly
50 55 60
Gly Tyr Gly Pro Gly Gly Val Gly Pro Gly Gly Ala Gly Gly Tyr Gly
65 70 75 80
Pro Gly Gly Ala Gly Gly Tyr Gly Pro Gly Gly Ser Gly Pro Gly Gly
85 90 95
Ala Gly Pro Gly Gly Ala Gly Gly Glu Gly Pro Val Thr Val Asp Val
100 105 110
Asp Val Thr Val Gly Pro Glu Gly Val Gly Gly Gly Pro Gly Gly Ala
115 120 125
Gly Pro Gly Gly Ala Gly Phe Gly Pro Gly Gly Gly Ala Gly Phe Gly
130 135 140
Pro Gly Gly Ala Pro Gly Ala Pro Gly Gly Pro Gly Gly Pro Gly Gly
145 150 155 160
Pro Gly Gly Pro Gly Gly Pro Gly Gly Val Gly Pro Gly Gly Ala Gly
165 170 175
Gly Tyr Gly Pro Gly Gly Ala Gly Gly Val Gly Pro Ala Gly Thr Gly
180 185 190
Gly Phe Gly Pro Gly Gly Ala Gly Gly Phe Gly Pro Gly Gly Ala Gly
195 200 205
Gly Phe Gly Pro Gly Gly Ala Gly Gly Phe Gly Pro Ala Gly Ala Gly
210 215 220
Gly Tyr Gly Pro Gly Gly Val Gly Pro Gly Gly Ala Gly Gly Phe Gly
225 230 235 240
Pro Gly Gly Val Gly Pro Gly Gly Ser Gly Pro Gly Gly Ala Gly Gly
245 250 255
Glu Gly Pro Val Thr Val Asp Val Asp Val Ser Val
260 265
<210> 505
<211> 420
<212> PRT
<213> Nephila clavipes
<400> 505
Gly Val Ser Tyr Gly Pro Gly Gly Ala Gly Gly Pro Tyr Gly Pro Gly
1 5 10 15
Gly Pro Tyr Gly Pro Gly Gly Glu Gly Pro Gly Gly Ala Gly Gly Pro
20 25 30
Tyr Gly Pro Gly Gly Val Gly Pro Gly Gly Ser Gly Pro Gly Gly Tyr
35 40 45
Gly Pro Gly Gly Ala Gly Pro Gly Gly Tyr Gly Pro Gly Gly Ser Gly
50 55 60
Pro Gly Gly Tyr Gly Pro Gly Gly Ser Gly Pro Gly Gly Tyr Gly Pro
65 70 75 80
Gly Gly Ser Gly Pro Gly Gly Tyr Gly Pro Gly Gly Ser Gly Pro Gly
85 90 95
Gly Tyr Gly Pro Gly Gly Tyr Gly Pro Gly Gly Ser Gly Pro Gly Gly
100 105 110
Ser Gly Pro Gly Gly Ser Gly Pro Gly Gly Tyr Gly Pro Gly Gly Thr
115 120 125
Gly Pro Gly Gly Ser Gly Pro Gly Gly Tyr Gly Pro Gly Gly Ser Gly
130 135 140
Pro Gly Gly Ser Gly Pro Gly Gly Tyr Gly Pro Gly Gly Ser Gly Pro
145 150 155 160
Gly Gly Phe Gly Pro Gly Gly Ser Gly Pro Gly Gly Tyr Gly Pro Gly
165 170 175
Gly Ser Gly Pro Gly Gly Ala Gly Pro Gly Gly Val Gly Pro Gly Gly
180 185 190
Phe Gly Pro Gly Gly Ala Gly Pro Gly Gly Ala Ala Pro Gly Gly Ala
195 200 205
Gly Pro Gly Gly Ala Gly Pro Gly Gly Ala Gly Pro Gly Gly Ala Gly
210 215 220
Pro Gly Gly Ala Gly Pro Gly Gly Ala Gly Pro Gly Gly Ala Gly Gly
225 230 235 240
Ala Gly Gly Ala Gly Gly Ser Gly Gly Ala Gly Gly Ser Gly Gly Thr
245 250 255
Thr Ile Ile Glu Asp Leu Asp Ile Thr Ile Asp Gly Ala Asp Gly Pro
260 265 270
Ile Thr Ile Ser Glu Glu Leu Pro Ile Ser Gly Ala Gly Gly Ser Gly
275 280 285
Pro Gly Gly Ala Gly Pro Gly Gly Val Gly Pro Gly Gly Ser Gly Pro
290 295 300
Gly Gly Val Gly Pro Gly Gly Ser Gly Pro Gly Gly Val Gly Pro Gly
305 310 315 320
Gly Ser Gly Pro Gly Gly Val Gly Pro Gly Gly Ala Gly Gly Pro Tyr
325 330 335
Gly Pro Gly Gly Ser Gly Pro Gly Gly Ala Gly Gly Ala Gly Gly Pro
340 345 350
Gly Gly Ala Tyr Gly Pro Gly Gly Ser Tyr Gly Pro Gly Gly Ser Gly
355 360 365
Gly Pro Gly Gly Ala Gly Gly Pro Tyr Gly Pro Gly Gly Glu Gly Pro
370 375 380
Gly Gly Ala Gly Gly Pro Tyr Gly Pro Gly Gly Ala Gly Gly Pro Tyr
385 390 395 400
Gly Pro Gly Gly Ala Gly Gly Pro Tyr Gly Pro Gly Gly Glu Gly Gly
405 410 415
Pro Tyr Gly Pro
420
<210> 506
<211> 376
<212> PRT
<213> Latrodectus hesperus
<400> 506
Gly Ile Asn Val Asp Ser Asp Ile Gly Ser Val Thr Ser Leu Ile Leu
1 5 10 15
Ser Gly Ser Thr Leu Gln Met Thr Ile Pro Ala Gly Gly Asp Asp Leu
20 25 30
Ser Gly Gly Tyr Pro Gly Gly Phe Pro Ala Gly Ala Gln Pro Ser Gly
35 40 45
Gly Ala Pro Val Asp Phe Gly Gly Pro Ser Ala Gly Gly Asp Val Ala
50 55 60
Ala Lys Leu Ala Arg Ser Leu Ala Ser Thr Leu Ala Ser Ser Gly Val
65 70 75 80
Phe Arg Ala Ala Phe Asn Ser Arg Val Ser Thr Pro Val Ala Val Gln
85 90 95
Leu Thr Asp Ala Leu Val Gln Lys Ile Ala Ser Asn Leu Gly Leu Asp
100 105 110
Tyr Ala Thr Ala Ser Lys Leu Arg Lys Ala Ser Gln Ala Val Ser Lys
115 120 125
Val Arg Met Gly Ser Asp Thr Asn Ala Tyr Ala Leu Ala Ile Ser Ser
130 135 140
Ala Leu Ala Glu Val Leu Ser Ser Ser Gly Lys Val Ala Asp Ala Asn
145 150 155 160
Ile Asn Gln Ile Ala Pro Gln Leu Ala Ser Gly Ile Val Leu Gly Val
165 170 175
Ser Thr Thr Ala Pro Gln Phe Gly Val Asp Leu Ser Ser Ile Asn Val
180 185 190
Asn Leu Asp Ile Ser Asn Val Ala Arg Asn Met Gln Ala Ser Ile Gln
195 200 205
Gly Gly Pro Ala Pro Ile Thr Ala Glu Gly Pro Asp Phe Gly Ala Gly
210 215 220
Tyr Pro Gly Gly Ala Pro Thr Asp Leu Ser Gly Leu Asp Met Gly Ala
225 230 235 240
Pro Ser Asp Gly Ser Arg Gly Gly Asp Ala Thr Ala Lys Leu Leu Gln
245 250 255
Ala Leu Val Pro Ala Leu Leu Lys Ser Asp Val Phe Arg Ala Ile Tyr
260 265 270
Lys Arg Gly Thr Arg Lys Gln Val Val Gln Tyr Val Thr Asn Ser Ala
275 280 285
Leu Gln Gln Ala Ala Ser Ser Leu Gly Leu Asp Ala Ser Thr Ile Ser
290 295 300
Gln Leu Gln Thr Lys Ala Thr Gln Ala Leu Ser Ser Val Ser Ala Asp
305 310 315 320
Ser Asp Ser Thr Ala Tyr Ala Lys Ala Phe Gly Leu Ala Ile Ala Gln
325 330 335
Val Leu Gly Thr Ser Gly Gln Val Asn Asp Ala Asn Val Asn Gln Ile
340 345 350
Gly Ala Lys Leu Ala Thr Gly Ile Leu Arg Gly Ser Ser Ala Val Ala
355 360 365
Pro Arg Leu Gly Ile Asp Leu Ser
370 375
<210> 507
<211> 200
<212> PRT
<213> Argiope trifasciata
<400> 507
Gly Ala Gly Tyr Thr Gly Pro Ser Gly Pro Ser Thr Gly Pro Ser Gly
1 5 10 15
Tyr Pro Gly Pro Leu Gly Gly Gly Ala Pro Phe Gly Gln Ser Gly Phe
20 25 30
Gly Gly Ser Ala Gly Pro Gln Gly Gly Phe Gly Ala Thr Gly Gly Ala
35 40 45
Ser Ala Gly Leu Ile Ser Arg Val Ala Asn Ala Leu Ala Asn Thr Ser
50 55 60
Thr Leu Arg Thr Val Leu Arg Thr Gly Val Ser Gln Gln Ile Ala Ser
65 70 75 80
Ser Val Val Gln Arg Ala Ala Gln Ser Leu Ala Ser Thr Leu Gly Val
85 90 95
Asp Gly Asn Asn Leu Ala Arg Phe Ala Val Gln Ala Val Ser Arg Leu
100 105 110
Pro Ala Gly Ser Asp Thr Ser Ala Tyr Ala Gln Ala Phe Ser Ser Ala
115 120 125
Leu Phe Asn Ala Gly Val Leu Asn Ala Ser Asn Ile Asp Thr Leu Gly
130 135 140
Ser Arg Val Leu Ser Ala Leu Leu Asn Gly Val Ser Ser Ala Ala Gln
145 150 155 160
Gly Leu Gly Ile Asn Val Asp Ser Gly Ser Val Gln Ser Asp Ile Ser
165 170 175
Ser Ser Ser Ser Phe Leu Ser Thr Ser Ser Ser Ser Ala Ser Tyr Ser
180 185 190
Gln Ala Ser Ala Ser Ser Thr Ser
195 200
<210> 508
<211> 357
<212> PRT
<213> Uloborus diversus
<400> 508
Gly Ala Ser Ala Ala Asp Ile Ala Thr Ala Ile Ala Ala Ser Val Ala
1 5 10 15
Thr Ser Leu Gln Ser Asn Gly Val Leu Thr Ala Ser Asn Val Ser Gln
20 25 30
Leu Ser Asn Gln Leu Ala Ser Tyr Val Ser Ser Gly Leu Ser Ser Thr
35 40 45
Ala Ser Ser Leu Gly Ile Gln Leu Gly Ala Ser Leu Gly Ala Gly Phe
50 55 60
Gly Ala Ser Ala Gly Leu Ser Ala Ser Thr Asp Ile Ser Ser Ser Val
65 70 75 80
Glu Ala Thr Ser Ala Ser Thr Leu Ser Ser Ser Ala Ser Ser Thr Ser
85 90 95
Val Val Ser Ser Ile Asn Ala Gln Leu Val Pro Ala Leu Ala Gln Thr
100 105 110
Ala Val Leu Asn Ala Ala Phe Ser Asn Ile Asn Thr Gln Asn Ala Ile
115 120 125
Arg Ile Ala Glu Leu Leu Thr Gln Gln Val Gly Arg Gln Tyr Gly Leu
130 135 140
Ser Gly Ser Asp Val Ala Thr Ala Ser Ser Gln Ile Arg Ser Ala Leu
145 150 155 160
Tyr Ser Val Gln Gln Gly Ser Ala Ser Ser Ala Tyr Val Ser Ala Ile
165 170 175
Val Gly Pro Leu Ile Thr Ala Leu Ser Ser Arg Gly Val Val Asn Ala
180 185 190
Ser Asn Ser Ser Gln Ile Ala Ser Ser Leu Ala Thr Ala Ile Leu Gln
195 200 205
Phe Thr Ala Asn Val Ala Pro Gln Phe Gly Ile Ser Ile Pro Thr Ser
210 215 220
Ala Val Gln Ser Asp Leu Ser Thr Ile Ser Gln Ser Leu Thr Ala Ile
225 230 235 240
Ser Ser Gln Thr Ser Ser Ser Val Asp Ser Ser Thr Ser Ala Phe Gly
245 250 255
Gly Ile Ser Gly Pro Ser Gly Pro Ser Pro Tyr Gly Pro Gln Pro Ser
260 265 270
Gly Pro Thr Phe Gly Pro Gly Pro Ser Leu Ser Gly Leu Thr Gly Phe
275 280 285
Thr Ala Thr Phe Ala Ser Ser Phe Lys Ser Thr Leu Ala Ser Ser Thr
290 295 300
Gln Phe Gln Leu Ile Ala Gln Ser Asn Leu Asp Val Gln Thr Arg Ser
305 310 315 320
Ser Leu Ile Ser Lys Val Leu Ile Asn Ala Leu Ser Ser Leu Gly Ile
325 330 335
Ser Ala Ser Val Ala Ser Ser Ile Ala Ala Ser Ser Ser Gln Ser Leu
340 345 350
Leu Ser Val Ser Ala
355
<210> 509
<211> 32
<212> PRT
<213> Euprosthenops australis
<400> 509
Gly Gly Gln Gly Gly Gln Gly Gln Gly Arg Tyr Gly Gln Gly Ala Gly
1 5 10 15
Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
20 25 30
<210> 510
<211> 42
<212> PRT
<213> Tetragnatha kauaiensis
<400> 510
Gly Gly Leu Gly Gly Gly Gln Gly Ala Gly Gln Gly Gly Gln Gln Gly
1 5 10 15
Ala Gly Gln Gly Gly Tyr Gly Ser Gly Leu Gly Gly Ala Gly Gln Gly
20 25 30
Ala Ser Ala Ala Ala Ala Ala Ala Ala Ala
35 40
<210> 511
<211> 42
<212> PRT
<213> Argiope aurantia
<400> 511
Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln Gly
1 5 10 15
Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Leu Gly Pro Tyr Gly
20 25 30
Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala
35 40
<210> 512
<211> 46
<212> PRT
<213> Deinopis spinosa
<400> 512
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 Ser Gly Gln
20 25 30
Gln Gly Pro Ala Gly Ala Ala Ala Ala Ala Ala Ala Ala Ala
35 40 45
<210> 513
<211> 42
<212> PRT
<213> Nephila clavata
<400> 513
Gly Pro Gly Gly Tyr Gly Leu Gly Gln Gln Gly Pro Gly Gln Gln Gly
1 5 10 15
Pro Gly Gln Gln Gly Pro Ala Gly Tyr Gly Pro Ser Gly Leu Ser Gly
20 25 30
Pro Gly Gly Ala Ala Ala Ala Ala Ala Ala
35 40
<210> 514
<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> 514
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
1010 1015 1020
Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa
1025 1030 1035
Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa
1040 1045 1050
Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala
1055 1060 1065
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr
1070 1075 1080
Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa
1085 1090 1095
Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa
1100 1105 1110
Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa
1115 1120 1125
Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa
1130 1135 1140
Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala
1145 1150 1155
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr
1160 1165 1170
Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa
1175 1180 1185
Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa
1190 1195 1200
Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa
1205 1210 1215
Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa
1220 1225 1230
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
1250 1255 1260
Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa
1265 1270 1275
Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa
1280 1285 1290
Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa
1295 1300 1305
Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa
1310 1315 1320
Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala
1325 1330 1335
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr
1340 1345 1350
Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa
1355 1360 1365
Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa
1370 1375 1380
Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa
1385 1390 1395
Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa
1400 1405 1410
Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala
1415 1420 1425
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr
1430 1435 1440
Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa
1445 1450 1455
Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa
1460 1465 1470
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
1490 1495 1500
Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala
1505 1510 1515
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr
1520 1525 1530
Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa
1535 1540 1545
Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa
1550 1555 1560
Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa
1565 1570 1575
Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa
1580 1585 1590
Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala
1595 1600 1605
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr
1610 1615 1620
Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa
1625 1630 1635
Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa
1640 1645 1650
Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa
1655 1660 1665
Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa
1670 1675 1680
Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala
1685 1690 1695
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr
1700 1705 1710
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
1730 1735 1740
Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa
1745 1750 1755
Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa
1760 1765 1770
Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala
1775 1780 1785
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
1790 1795 1800
<210> 515
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 515
Ser Gly Gly Gln Gln
1 5
<210> 516
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 516
Gly Ala Gly Gln Gln
1 5
<210> 517
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 517
Gly Gln Gly Pro Tyr
1 5
<210> 518
<211> 4
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 518
Ala Gly Gln Gln
1
<210> 519
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<220>
<221> MISC_FEATURE
<222> (1)..(10)
<223> This sequence may encompass 2-10 residues
<400> 519
Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala
1 5 10
<210> 520
<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> 520
His His His His His His His His
1 5
<210> 521
<211> 70
<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 "GPG-X1" repeating
units, wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ"
or "SQ," and some positions may be absent
<400> 521
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
65 70
<210> 522
<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> 522
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
Claims (50)
- YPS1-1 프로테아제 및 YPS1-2 프로테아제의 활성이 약화 또는 제거되었으며, 재조합 폴리펩티드를 발현시키는 피키아 파스토리스 (Pichia pastoris) 미생물.
- 청구항 1에 있어서, 상기 YPS1-1 프로테아제는 서열 번호: 67에 최소한 95% 동일한 폴리펩티드 서열을 포함하는, 미생물.
- 청구항 1에 있어서, 상기 YPS1-1 프로테아제는 서열 번호: 67을 포함하는, 미생물.
- 청구항 1 또는 청구항 2에 있어서, 상기 YPS1-1 프로테아제는 YPS1-1 유전자에 의해 인코드되는, 미생물.
- 청구항 4에 있어서, 상기 YPS1-1 유전자는, 서열 번호: 1에 최소한 95% 동일한 폴리뉴클레오티드 서열을 포함하는, 미생물.
- 청구항 4에 있어서, 상기 YPS1-1 유전자는 서열 번호: 1의 15, 20, 25, 30, 40, 또는 50개 이상의 인접 뉴클레오티드를 포함하는, 미생물.
- 청구항 4에 있어서, 상기 YPS1-1 유전자는 서열 번호: 1을 포함하는, 미생물.
- 청구항 4에 있어서, 상기 YPS1-1 유전자는 상기 미생물의 좌위 PAS_chr4_0584에 존재하는, 미생물.
- 전술한 청구항 중 어느 한 항에 있어서, 상기 YPS1-2 프로테아제는 서열 번호: 68에 최소한 95% 동일한 폴리펩티드 서열을 포함하는, 미생물.
- 청구항 9에 있어서, 상기 YPS1-2 프로테아제는 서열 번호: 68을 포함하는, 미생물.
- 전술한 청구항 중 어느 한 항에 있어서, 상기 YPS1-2 프로테아제는 YPS1-2 유전자에 의해 인코드되는, 미생물.
- 청구항 11에 있어서, 상기 YPS1-2 유전자는, 서열 번호: 2에 최소한 95% 동일한 폴리뉴클레오티드 서열을 포함하는, 미생물.
- 청구항 11에 있어서, 상기 YPS1-2 유전자는 서열 번호: 2의 15, 20, 25, 30, 40, 또는 50개 이상의 인접 뉴클레오티드를 포함하는, 미생물.
- 청구항 11에 있어서, 상기 YPS1-2 유전자는 서열 번호: 2를 포함하는, 미생물.
- 청구항 11에 있어서, 상기 YPS1-2 유전자는 상기 미생물의 좌위 PAS_chr3_1157에 존재하는, 미생물.
- 전술한 청구항 중 어느 한 항에 있어서, 상기 YPS1-1 유전자 또는 상기 YPS1-2 유전자, 또는 둘 모두는 돌연변이 되었거나 녹아웃되어 있는, 미생물.
- 전술한 청구항 중 어느 한 항에 있어서, 상기 미생물은 재조합 단백질을 발현하는, 미생물.
- 청구항 17에 있어서, 상기 재조합 단백질은 실크 단백질의 하나 이상의 블록 폴리펩티드 서열을 포함하는, 미생물.
- 청구항 17에 있어서, 상기 재조합 단백질은 실크-유사 폴리펩티드를 포함하는, 미생물.
- 청구항 19에 있어서, 상기 실크-유사 폴리펩티드는 하나 이상의 반복 서열들 {GGY-[GPG-X1]n1-GPS-(A)n2}n3 (서열 번호: 514)을 포함하는 미생물, 이 때
X1 = SGGQQ (서열 번호: 515) 또는 GAGQQ (서열 번호: 516) 또는 GQGPY (서열 번호: 517) 또는 AGQQ (서열 번호: 518) 또는 SQ이고;
n1은 4 내지 8이고;
n2는 6 내지 20이고; 그리고
n3은 2 내지 20임. - 청구항 19에 있어서, 상기 실크-유사 폴리펩티드는 서열 번호: 462에 의해 인코드되는 폴리펩티드 서열을 포함하는, 미생물.
- 전술한 청구항 중 어느 한 항에 있어서, 하나 이상의 추가 프로테아제들의 활성은 약화 또는 제거되어 있는, 미생물.
- 청구항 22에 있어서, 상기 하나 이상의 추가 프로테아제는 YPS1-5, MCK7, 또는 YPS1-3을 포함하는, 미생물.
- 청구항 23에 있어서, 상기 YPS1-5 유전자는 상기 미생물의 좌위 PAS_chr3_0688에 존재하는, 미생물.
- 청구항 23에 있어서, 상기 MCK7 프로테아제는 서열 번호: 7에 최소한 95% 동일한 폴리뉴클레오티드 서열을 포함하는 MCK7 유전자에 의해 인코드되는, 미생물.
- 청구항 23에 있어서, 상기 MCK7 유전자는 서열 번호: 7의 15, 20, 25, 30, 40, 또는 50개 이상의 인접 뉴클레오티드를 포함하는, 미생물.
- 청구항 23에 있어서, 상기 MCK7 유전자는 서열 번호: 7을 포함하는, 미생물.
- 청구항 23에 있어서, 상기 MCK7 유전자는 상기 미생물의 좌위 PAS_chr1-1_0379에 존재하는, 미생물.
- 청구항 23에 있어서, 상기 YPS1-3 프로테아제는 서열 번호: 3에 최소한 95% 동일한 폴리뉴클레오티드 서열을 포함하는 YPS1-3 유전자에 의해 인코드되는, 미생물.
- 청구항 23에 있어서, 상기 YPS1-3 유전자는 서열 번호: 3의 15, 20, 25, 30, 40, 또는 50개 이상의 인접 뉴클레오티드를 포함하는, 미생물.
- 청구항 23에 있어서, 상기 YPS1-3 유전자는 서열 번호: 3을 포함하는, 미생물.
- 청구항 23에 있어서, 상기 YPS1-3 유전자는 상기 미생물의 좌위 PAS_chr3_0299에 존재하는, 미생물.
- 청구항 22에 있어서, 상기 하나 이상의 추가 프로테아제는 서열 번호: 68 - 130으로 구성된 그룹에서 선택된 폴리펩티드 서열에 최소한 95% 동일한 폴리펩티드 서열을 포함하는, 미생물.
- 청구항 22에 있어서, 상기 하나 이상의 추가 프로테아제는 서열 번호: 68 - 130으로 구성된 그룹에서 선택된 폴리펩티드 서열을 포함하는, 미생물.
- 청구항 22에 있어서, 상기 하나 이상의 추가 프로테아제는 서열 번호: 3 - 66으로 구성된 그룹에서 선택된 폴리뉴클레오티드 서열에 최소한 95% 동일한 폴리뉴클레오티드 서열에 의해 인코드되는, 미생물.
- 청구항 22에 있어서, 상기 하나 이상의 추가 프로테아제는 서열 번호: 3 - 66으로 구성된 그룹에서 선택된 폴리뉴클레오티드 서열의 15, 20, 25, 30, 40, 또는 50개 이상의 인접 뉴클레오티드를 포함하는 폴리뉴클레오티드 서열에 의해 인코드되는, 미생물.
- 청구항 22-36 중 어느 한 항에 있어서, 상기 미생물은 3X, 4X 또는 5X 프로테아제 녹아웃을 포함하는, 미생물.
- 서열 번호: 1을 포함하는 YPS1-1 유전자 및 서열 번호: 2를 포함하는 YPS1-2 유전자의 돌연변이 또는 결실에 의해 감소된 YPS1-1 및 YPS1-2 활성을 포함하는 피키아 파스토리스 (Pichia pastoris) 조작된 미생물로서, 이 때 상기 미생물은 서열 번호: 462에 의해 인코드되는 폴리펩티드 서열을 포함하는 재조합 발현 단백질을 추가로 포함하는, 미생물.
- 청구항 1-38 중 어느 한 항의 미생물을 포함하는 세포 배양물.
- 청구항 17-38 중 어느 한 항의 미생물을 포함하는 세포 배양물로서, 상기 재조합 발현 단백질은 그 YPS1-1 및 YPS1-2 활성이 약화 또는 제거되지 않은 것 외에는 동일한 피키아 파스토리스 (Pichia pastoris) 미생물을 포함하는 세포 배양물보다 덜 분해되는, 세포 배양물.
- 다음 단계를 포함하는, 분해가 감소된 재조합 단백질의 제조 방법:
청구항 17-37 중 어느 한 항의 미생물을 재조합 발현 단백질의 발현에 적합한 조건하의 배양 배지에서 배양하는 단계; 및
상기 미생물 또는 배양 배지로부터 재조합 단백질을 단리하는 단계. - 청구항 41에 있어서, 상기 재조합 단백질은 상기 미생물로부터 분비되며, 상기 재조합 단백질을 단리하는 단계는 상기 분비된 재조합 단백질을 포함하는 배양 배지를 수집하는 단계를 포함하는, 방법.
- 청구항 41에 있어서, 상기 재조합 단백질은 상기 YPS1-1 및 상기 YPS1-2 프로테아제 활성이 약화 또는 제거되지 않은 것 이외에는 동일한 미생물에 의해 제조된 상기 재조합 단백질과 비교하여 감소된 분해 수준을 가지는, 방법.
- YPS1-1 단백질 및 YPS1-2 단백질을 인코드하는 유전자를 녹아웃 또는 돌연변이시키는 단계를 포함하는, 재조합 발현 단백질의 분해를 감소시키기 위한, 피키아 파스토리스 변형 방법.
- 청구항 44에 있어서, YPS1-3 단백질, YPS1-5 단백질, 또는 MCK7 단백질을 인코드하는 하나 이상의 추가 유전자들을 녹아웃 또는 돌연변이하는 단계를 추가로 포함하는, 방법.
- 청구항 44에 있어서, 서열 번호: 68-130으로 구성된 그룹에서 선택된 폴리펩티드를 포함하는 단백질을 인코드하는 하나 이상의 유전자들을 녹아웃하는 단계를 추가로 포함하는, 방법.
- 청구항 44에 있어서, 상기 재조합 발현 단백질은 2, 3, 4, 5, 6, 7, 8, 9, 또는 10개 이상의 인접 알라닌 잔기들을 포함하는 폴리A 서열 (서열 번호: 519)을 포함하는, 방법.
- 청구항 44에 있어서, 상기 재조합 발현 단백질은 실크-유사 폴리펩티드를 포함하는, 방법.
- 청구항 48에 있어서, 상기 실크-유사 폴리펩티드는 하나 이상의 반복 서열들 {GGY-[GPG-X1]n1-GPS-(A)n2}n3 (서열 번호: 514)을 포함하는 방법, 이 때
X1 = SGGQQ (서열 번호: 515) 또는 GAGQQ (서열 번호: 516) 또는 GQGPY (서열 번호: 517) 또는 AGQQ (서열 번호: 518) 또는 SQ이고;
n1은 4 내지 8이고;
n2는 6 내지 20이고; 그리고
n3은 2 내지 20임. - 청구항 44에 있어서, 상기 재조합 발현 단백질은 서열 번호: 462에 의해 인코드되는 폴리펩티드 서열을 포함하는, 방법.
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J. Ind. Microbiol. Biotechnol.,제40권,589-599면(2013) 1부.* * |
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KR102558303B1 (ko) | 2023-07-21 |
MX2020003362A (es) | 2020-07-29 |
EP3692054A1 (en) | 2020-08-12 |
CN111315763A (zh) | 2020-06-19 |
WO2019070246A1 (en) | 2019-04-11 |
EP3692054A4 (en) | 2021-06-09 |
JP7246102B2 (ja) | 2023-03-27 |
AU2017434920B2 (en) | 2022-02-10 |
JP2021503275A (ja) | 2021-02-12 |
AU2022202534A1 (en) | 2022-05-12 |
AU2017434920A1 (en) | 2020-05-07 |
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