KR100810699B1 - 항원 유전자 서열의 동정 방법 - Google Patents
항원 유전자 서열의 동정 방법 Download PDFInfo
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- KR100810699B1 KR100810699B1 KR1020017006157A KR20017006157A KR100810699B1 KR 100810699 B1 KR100810699 B1 KR 100810699B1 KR 1020017006157 A KR1020017006157 A KR 1020017006157A KR 20017006157 A KR20017006157 A KR 20017006157A KR 100810699 B1 KR100810699 B1 KR 100810699B1
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- KR
- South Korea
- Prior art keywords
- ile
- lys
- leu
- asn
- glu
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Abstract
본 발명은 잠재적 백신 항원의 유전자 서열을 동정하는 방법에 관한 것이다. 또한, 본 발명에는 유전자 서열 및 이 유전자 서열로 암호화되는 폴리펩티드와, 동물에서 보호 면역 반응을 유도하기 위한 이러한 서열의 사용이 포함된다. 본 발명은 특히 마이코플라스마, 바람직하게는 마이코플라스마 하이오뉴모니아의 잠재적 항원 유전자 서열 동정에 관한 것이다. 본 발명의 일 실시형태에 따르면, 발현 벡터의 뉴클레오티드 서열로부터 번역된 발현 단백질의 동정 방법이 제공되며, 상기 방법은 뉴클레오티드 서열로부터 번역된 단백질과 공동-발현되는 마커를 사용하는 것을 포함하여 이루어진다. 본 발명의 다른 실시형태에 따르면, 뉴클레오티드 서열 시료로부터 질환의 치료 항원 단백질을 암호화하는 치료 항원 유전자 서열을 동정하는 방법이 제공된다. 마커는 폴리히스티딘 태그가 바람직하다.
Description
본 발명은 잠재적 백신 항원의 유전자 서열을 동정하는 방법에 관한 것이다. 또한, 유전자 서열 및 이 유전자 서열로 암호화되는 폴리펩티드와, 동물에서 보호 면역 반응을 유도하기 위한 이러한 서열의 사용에 관한 것이다. 특히 본 발명은 마이코플라스마, 바람직하게는 마이코플라스마 하이오뉴모니아(Mycoplasma hyopneumoniae)의 잠재적 항원 유전자 서열의 동정에 관한 것이다.
병원균에 대하여 백신이 성공을 거두기 위해서는, 숙주 면역계에 쉽게 접근할 수 있는 병원균의 적당한 항원을 동정해야 한다. 항원이 일단 동정되면, 병원균에 대한 보호의 기본을 형성할 수 있다.
최근 동물 건강 회사(Animal Health companies)를 통하여 다수의 백신이 상업화되고 있다. 많은 백신은 불활성화된 전체 세포 박테린에 기초한다. 이러한 백신이 합리적인 수준의 효능을 제공한다고 하더라도 개선의 여지가 상당하다. 따라서, 전체 세포 또는 전체 세포 단편에 기초하지 않는 백신을 개발함으로써 현재 이용가능한 백신을 개선할 수 있다.
병원균에 대한 백신을 생성하는 다른 방법에는 다양한 단백질의 불활성화된 항원 조혼합물을 사용하는 것이 포함된다. 그러나, 이러한 방법은 숙주에 다양한 항원을 제공하지만, 숙주 면역계에 쉽게 접근가능한 대부분의 단백질이 다른 항원에 의해 방해를 받으므로 이 중 어떤 방법도 적당한 총체적인 보호를 제공하지 못한다는 문제점이 있다. 또한, 일부 병원균은 까다로운 필요조건 때문에 증식하기 어렵거나 비용이 많이 든다. 어떤 병원균은 또한 취급하기 위험하다. 따라서, 세포 또는 박테리아의 증식 및 전체 세포 또는 전체 세포의 단편의 처리를 필요로 하지 않는 백신은 더 안전하고, 값싸고, 아마 더 효능있는 백신을 제공한다.
더 깨끗하고 더 특이적인 백신을 얻는 한 방법은 재조합 보호 항원을 사용하는 것이다. 특이적 항원을 제공함으로써, 숙주 면역계에 쉽게 접근할 수 있는 항원만을 사용할 수 있다.
문제는 잠재적 항원의 동정이다. 한 가지 방법은 유전자 라이브러리를 만드는 것이다. 그러나, 이 라이브러리로부터 잠재적 보호 항원을 포함할 수 있는 서열을 결정하는 것은 매우 많은 시간이 소모된다.
다수의 잠재적인 항원 유전자를 통해 질병으로부터 어떤 수준의 보호를 제공하는 이들의 효능을 효과적으로 선별하기 위해, 이들을 초기에 발현 클론으로서 클로닝하는 것이 유용하다. 이 방법에서는 지루하고 시간 낭비적인 클론 분석 및 이어지는 발현 서브클로닝이 불필요하다. 항원 발견의 전체 공정은 가속화된다. 이제 본 출원인들은, 처음 조사된 클론이 재조합 단백질을 발현하고 있었음을 확인하기 위한 신규한 방법을 제공한다.
먼저, 유용한 단백질에 특이적이거나 유용한 단백질이 풍부한 항체를 사용하 여 특정 단백질의 전부 또는 일부를 발현하는 클론의 발현 라이브러리를 선별하였다.
또한, 단백질을 암호화하는 DNA 서열을 동정함으로써, 적당한 발현 비히클을 사용하여 재조합 DNA 분자를 형성하고 이러한 재조합 DNA 분자를 사용하여 적당한 숙주(예를 들어, 원핵 또는 진핵 숙주)를 형질전환시킬 수 있다. 이어서, 형질전환된 숙주를 배양하여, 숙주가 DNA 서열을 발현하고 원하는 단백질을 생성하도록 할 수 있다.
생성 후 분리된 단백질, 활성 성분 또는 이의 조합물을 보호 면역 반응을 일으키기에 충분한 양으로 투여(예를 들어, 주사)하여 감염에 대한 면역성을 부여하는 수단을 제공한다.
마이코플라스마 하이오뉴모니아는, 동물 건강 회사에 의해 백신이 상업화된 병원균 중 하나이다. 이 병원균은 돼지에 동물지방병성 폐렴을 유발한다. 치사시키는 경우는 드물지만, 심각한 병적 상태를 일으키고, 돼지의 음식 전환 효율을 크게 감소시켜 중량 증가를 감소시킴으로써 능률을 저하시키는 경우가 많다. 동물은 기침과 열의 증세를 보이고, 기회성 미생물에 의해 종종 2차 감염되기 쉽다.
마이코플라스마 하이오뉴모니아에 대한 백신을 제공하기 위하여 많은 시도가 있었으나 성공을 거두지 못하였다. 특히, 열 불활성화된, 살아있는 마이코플라스마 또는 이의 추출물을 사용하면 보호를 제공함에 효과적이지 못한 것으로 판명되었다. 불활성화된 전체 세포 박테린에 기초한 백신 중 일부는 어느 수준의 효능을 보이지만 개선의 여지가 있다.
또한, 마이코플라스마 하이오뉴모니아는 까다로운 필요조건 때문에 증식시키기 어렵고 비용이 많이 든다. 따라서, 현재 사용할 수 있는 백신들은 전체 세포 또는 전체 세포의 단편을 기초로 하지 않는 백신을 개발함으로써 개선될 수 있다.
따라서, 본 발명의 목적은 종래 기술의 문제점의 일부를 극복하거나 적어도 완화시키는 것이다.
본 발명의 일실시형태는 발현 벡터에서 뉴클레오티드 서열로부터 번역된 발현 단백질을 동정하는 방법을 제공하며, 상기 방법은 뉴클레오티드 서열로부터 번역된 단백질과 공동-발현되는 마커를 사용하는 것을 포함한다.
본 발명의 바람직한 실시형태는 발현 벡터에서 뉴클레오티드 서열에 의해 암호화된 발현 단백질을 동정하기 위한 폴리히스티딘 태그(polyHis tag)의 사용을 제공하며, 상기 폴리히스티딘 태그는 상기 단백질과 공동-발현된다.
본 발명의 다른 실시형태는 뉴클레오티드 서열의 혼합물로부터의 뉴클레오티드 서열에 의해 암호화된 발현 단백질을 동정하는 방법을 제공하며, 상기 방법은:
마커를 포함하는 발현 벡터를 제공하는 단계;
혼합물로부터 뉴클레오티드 서열을 발현 벡터로 도입시키는 단계; 및
발현 단백질과 공동-발현되는 마커를 포함하는 융합 단백질의 존재 여부를 확인함으로써 발현 벡터에 의해 발현된 발현 단백질을 동정하는 단계를 포함하여 이루어진다.
바람직한 실시형태에서 마커는 폴리히스티딘 태그이다.
다른 바람직한 실시형태에서, 발현 벡터는 발현 단백질을 포함하는 마커-융합 단백질을 발현하기 위해 숙주 세포로 유전자도입(transfect)된다. 마커 융합 단백질은 폴리히스티딘 태그 및 발현 단백질을 포함하는 폴리히스티딘 태그-융합 단백질인 것이 바람직하다. 발현 벡터 집단을 숙주 세포로 도입시키면 선별될 수 있는 게놈 또는 cDNA 라이브러리를 만들 수 있다.
이 방법의 다른 바람직한 실시형태는 융합 단백질에서 발현된 마커를 사용하여 발현 단백질을 정제하는 단계를 포함한다. 바람직한 마커는 폴리히스티딘 태그이다.
다른 실시형태는 상기 방법에 따라 동정된 정제된 재조합 단백질을 제공한다. 재조합 단백질은 발현 단백질인 것이 바람직하다.
다른 실시형태는 상기 방법에 따라 동정된 재조합 단백질을 암호화하는 정제된 뉴클레오티드 서열을 제공한다.
본 발명의 다른 실시형태는 뉴클레오티드 서열에 의해 암호화된 발현 단백질을 동정하는데 사용하기 위해 마커, 바람직하게는 폴리히스티딘 태그를 포함하는 발현 벡터를 제공한다.
본 발명의 또다른 실시형태는 발현 단백질을 동정하는데 사용하기 위해 마커, 바람직하게는 폴리히스티딘 태그를 포함하는 발현 벡터를 포함한 숙주를 제공한다.
본 발명의 다른 실시형태는 뉴클레오티드 서열의 시료로부터 항원 단백질을 암호화하는 유전자 서열을 동정하기 위한 방법을 제공하며, 상기 방법은:
마커를 포함하는 발현 벡터를 제공하는 단계;
시료로부터 뉴클레오티드 서열을 발현 벡터로 도입시키는 단계;
뉴클레오티드 서열에 의해 번역된 발현 단백질과 공동-발현되는 마커를 포함하는 융합 단백질의 존재 여부를 확인함으로써 발현 벡터에 의해 발현된 항원 발현 단백질을 동정하는 단계; 및
항원 발현 단백질을 동정하는 단계를 포함하여 이루어진다.
바람직한 마커는 폴리히스티딘 태그이다.
바람직한 실시형태에서, 이 방법은 발현 벡터에 의해 암호화된 항원 단백질의 유전자 서열을 결정하는 단계를 더 포함한다.
본 발명의 다른 실시형태는, 뉴클레오티드 서열의 라이브러리를 선별하는 방법을 제공하며, 상기 방법은:
뉴클레오티드 서열의 공급원을 제공하는 단계;
마커를 포함하는 발현 벡터를 제공하는 단계;
뉴클레오티드 서열을 발현 벡터로 도입시킴으로써 라이브러리를 만드는 단계;
뉴클레오티드 서열에 의해 번역된 발현 단백질과 공동-발현되는 마커를 포함하는 융합 단백질의 존재 여부를 확인함으로써 발현 벡터에 의해 발현된 발현 단백질을 동정하는 단계; 및
발현 단백질의 뉴클레오티드 서열을 확인하는 단계를 포함한다.
바람직한 마커는 폴리히스티딘 태그이다.
다른 실시형태는 발현 라이브러리에서 발현 클론들을 동정하기 위해 선별하는 방법을 제공하며, 상기 방법은:
뉴클레오티드 서열의 공급원을 제공하는 단계;
마커를 포함하는 발현 벡터를 제공하는 단계;
뉴클레오티드 서열을 발현 벡터로 도입시키는 단계;
발현 벡터를 숙주속으로 형질전환시켜 발현 라이브러리를 만드는 단계; 및
발현 단백질과 공동-발현되는 마커, 바람직하게는 폴리히스티딘 태그를 포함하는 융합 단백질의 발현을 검출하여 발현 클론의 위치를 확인하는 단계를 포함한다.
본 발명의 다른 실시형태는 뉴클레오티드 서열의 시료로부터 질병의 치료 항원 단백질을 암호화하는 치료 항원 유전자 서열을 동정하는 방법을 제공하며, 상기 방법은:
마커를 포함하는 발현 벡터를 제공하는 단계;
시료로부터 뉴클레오티드 서열을 발현 벡터로 도입시키는 단계;
뉴클레오티드 서열에 의해 번역된 발현 단백질과 공동-발현되는 마커를 포함하는 융합 단백질의 존재 여부를 확인함으로써 발현 벡터에 의해 발현된 항원 발현 단백질을 동정하는 단계;
항원 발현 단백질을 발현하는 발현 벡터를 동물에게 접종시키는 단계;
동물을 질병으로 감염시키는 단계;
백신접종에 의해 유도된 치료적 효과를 제공하는 발현 벡터 및 발현 단백질 을 동정하는 단계; 및
발현 벡터에 의해 암호화된 항원 발현 단백질의 유전자 서열을 확인하는 단계를 포함하여 이루어진다.
바람직한 마커는 폴리히스티딘 태그이다.
본 발명의 다른 바람직한 실시형태는 마이코플라스마, 바람직하게는 마이코플라스마 하이오뉴모니아의 폴리펩티드를 암호화하는 뉴클레오티드 서열에 대한 뉴클레오티드 서열의 라이브러리를 선별하는 방법을 제공하며, 상기 방법은:
마이코플라스마 시료로부터 뉴클레오티드 서열의 공급원을 제공하는 단계;
마커를 포함하는 발현 벡터를 제공하는 단계;
뉴클레오티드 서열을 발현 벡터에 도입시키는 단계;
뉴클레오티드 서열에 의해 번역된 발현 단백질과 공동-발현되는 마커, 바람직하게는 폴리히스티딘 태그를 포함하는 융합 단백질의 존재 여부를 확인함으로써 발현 벡터에 의해 발현된 마이코플라스마 발현 단백질을 동정하는 단계; 및
마이코플라스마, 바람직하게는 마이코플라스마 하이오뉴모니아의 발현 단백질의 뉴클레오티드 서열을 확인하는 단계를 포함하여 이루어진다.
바람직한 마커는 폴리히스티딘 태그이다.
바람직한 실시형태에서, 유전자 서열은 마이코플라스마, 바람직하게는 마이코플라스마 하이오뉴모니아의 항원 폴리펩티드를 암호화한다.
본 발명의 다른 실시형태는 마이코플라스마, 바람직하게는 마이코플라스마 하이오뉴모니아의 폴리펩티드를 암호화하는 뉴클레오티드 서열, 돌연변이체, 유사체, 유도체 또는 기능적으로 활성인 이의 단편을 제공하며, 상기 뉴클레오티드 서열은 상기 방법으로 동정된다. 뉴클레오티드 서열은 도 1a 내지 42 중의 어느 하나에 따른 서열, 및 돌연변이체, 유사체, 유도체 또는 기능적으로 활성인 이의 단편을 포함하는 것이 바람직하다. 더 상세하게는, 뉴클레오티드 서열은 SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:77, SEQ ID NO:79, SEQ ID NO:81 또는 SEQ ID NO:83 또는 돌연변이체, 유사체, 유도체 또는 기능적으로 활성인 이의 단편에 따른다.
본 발명의 또다른 실시형태는, 마이코플라스마, 바람직하게는 마이코플라스마 하이오뉴모니아의 폴리펩티드를 암호화하는 뉴클레오티드 서열, 돌연변이체, 유사체, 유도체 또는 기능적으로 활성인 이의 단편에 의해 암호화된 폴리펩티드를 제공하며, 상기 뉴클레오티드 서열은 상기 방법에 의해 동정된다. 폴리펩티드는 도 1a 내지 42 중의 어느 하나에 따른 서열, 돌연변이체, 유사체, 유도체 또는 기능적으로 활성인 이의 단편에 의해 암호화된 뉴클레오티드 서열에 의해 암호화되는 것이 바람직하다. 더 상세하게는, 폴리펩티드는 SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO: 62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO: 74, SEQ ID NO: 76, SEQ ID NO:78, SEQ ID NO:80, SEQ ID NO:82 또는 SEQ ID NO:84에 따른 아미노산 서열 또는 돌연변이체, 유사체, 유도체 또는 기능적으로 활성인 이의 단편을 가진다.
본 발명의 다른 실시형태는 상기 폴리펩티드 또는 뉴클레오티드 서열을 포함하는 조성물을 포함한다. 또한, 다른 실시형태는 상기 폴리펩티드 또는 뉴클레오티드 서열의 약제학적 조성물 및 백신 조성물을 포함한다.
본 발명의 다른 실시형태는 폴리펩티드에 대해 생성된 모노클로날 항체를 포함한다.
또한, 본 발명의 다른 실시형태는 마이코플라스마 감염을 치료하는 방법을 포함하며, 상기 방법은 상기 방법에 의해 동정된 폴리펩티드를 암호화하는 뉴클레오티드 서열 또는 뉴클레오티드 서열에 의해 암호화된 마이코플라스마의 항원 폴리펩티드를 유효량으로 투여하는 단계를 포함한다. 항원 폴리펩티드는 도 1a 내지 42 중의 어느 하나에 따른 뉴클레오티드 서열 또는 돌연변이체, 유사체, 유도체 또는 기능적으로 활성인 이의 단편에 의해 암호화되는 것이 바람직하다. 더 상세하게는, 뉴클레오티드 서열은 SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:77, SEQ ID NO:79, SEQ ID NO:81 또는 SEQ ID NO:83 또는 돌연변이체, 유사체, 유도체 또는 기능적으로 활성인 이의 단편에 따른다.
본 명세서의 상세한 설명 및 청구항 전체에서, "포함한다" 및 "포함하는" 및 "포함하여 이루어진다"와 같은 변형어는 다른 첨가체, 성분, 정수 또는 단계를 배제하는 의미가 아니다.
본 발명의 일 실시형태는 발현 벡터의 뉴클레오티드 서열로부터 번역된 발현 단백질을 동정하는 방법을 제공하며, 상기 방법은 뉴클레오티드 서열로부터 번역된 단백질과 공동-발현되는 마커의 사용을 포함한다.
바람직한 실시형태에서, 마커는 검출될 수 있는 임의의 마커이다. 모노클로날 항체 또는 특이적인 폴리클로날 항혈청으로 검출할 수 있다. 바람직한 마커는 작은, 바람직하게는 30 아미노산 이하인 것이 바람직하다. 가장 바람직한 마커는 폴리히스티딘 태그이다. 또한, 태그는 하기 태그들 중 하나일 수 있다:
(a) 시그마-알드리치사(Sigma-Aldrich Inc. USA)로부터의 플라스미드 벡터에 이용가능한 8 아미노산 태그 서열인 FLAG 태그,
(b) 암래드 코포레이션 주식회사(Amrad Corporation Ltd., Australia)로부터의 벡터에 이용가능한 I-SPY 에피토프 6 아미노산 태그,
(c) 혈구응집소 에피토프 9 아미노산 태그(Clontech Laboratories Inc. USA); 및
(d) c-Myc 에피토프 12 아미노산 태그(Clontech Laboratories Inc. USA).
마커가 폴리히스티딘 태그인 경우, 히스티딘 잔기의 수는 4 내지 8개인 것이 바람직하며, 6개인 것이 더 바람직하다. 적어도 4 내지 8개의 인접하는 히스티딘 잔기가 있다면, 총 10개 이상의 아미노산을 제공하는 폴리히스티딘 태그 앞에 4개 이상의 아미노산 잔기가 올 수 있다.
다수의 잠재적인 항원 유전자를 통해 질병으로부터 어느 수준의 보호를 제공하는 이들의 효능을 효과적으로 선별하기 위해, 이들을 초기에 발현 클론으로서 클로닝하는 것이 유용하다. 이 방법에서는 지루하고 시간 낭비적인 클론 분석 및 이어지는 발현 서브클로닝이 불필요하다. 항원 발견의 전체 공정은 가속화된다. 이제 본 출원인들은, 처음 조사된 클론이 재조합 단백질을 발현하고 있었음을 확인하기 위한 신규한 방법을 제공한다.
이것은 특히 유전자 라이브러리를 다루는 경우이다. 임의의 무작위 라이브러리에서 대부분의 클론들은 발현하기에 부정확한 방향에 존재하거나 또는 단백질을 발현하기에 잘못된 리딩 프레임에 존재한다. 발현 벡터에서 마커, 바람직하게는 폴리히스티딘 태그를 사용하면 마커, 바람직하게는 폴리히스티딘 태그 융합 단백질을 발현하는 클론의 발현을 효과적으로 동정할 수 있다.
재조합 마커-융합 단백질 또는 바람직하게는 폴리히스티딘 융합 단백질, 또는 단지 짧은 재조합 단백질을 생성하지 않는 클론에서, 암호화된 작은 마커 또는 폴리히스티딘 단백질은 숙주 세포 안에서 신속하게 분해되고, 잔존하는 임의의 마커 또는 폴리히스티딘 단백질은 콜로니 스크리닝을 위해 사용되는 막에 매우 약하게 결합한다. 따라서, 비-생산적인 클론은 콜로니 스크리닝에 부정적인 결과를 낳는 반면, 더 길게 태그된 재조합 단백질을 생성하는 클론은 긍정적인 신호를 제공할 수 있다. 따라서, 일반적인 게놈 발현 라이브러리는 복잡성이 상당히 감소될 수 있으므로, 더 빠르고 효율적인 스크리닝 및 이어서 원하는 클론의 사용을 가능하게 한다.
단백질을 발현하는 이러한 클론들은 잠재적인 보호 항원으로 생각되고, 클론을 구성하고 선별하는데 사용되는 전략 때문에, 원래 분리된 클론은 즉시 유전자 백신 접종을 위한 정제된 플라스미드 DNA의 형태, 또는 정제된 마커-융합 재조합 단백질, 바람직하게는 폴리히스티딘 정제된 재조합 융합 단백질로서 백신 실험에서 사용될 수 있다.
마커가 폴리히스티딘 태그 영역인 경우, 이는 이 영역을 포함한 임의의 공급원으로부터 유도될 수 있다. 예를 들어, 폴리히스티딘 태그를 암호화하는 벡터 pQE30, pQE31 및 pQE32(Qiagen Pty. Ltd. Australia)의 영역이 사용될 수 있다. 폴리히스티딘 태그의 다른 공급원은 노바겐사(Novagen Inc., USA(pET-1.9-33))로부터 또는 폴리히스티딘 태그를 합성 제조하여 얻을 수 있다.
본 발명의 다른 실시형태는 뉴클레오티드 서열의 혼합물로부터의 뉴클레오티드 서열로부터 번역된 발현 단백질을 동정하기 위한 방법을 제공하며, 상기 방법은:
마커를 포함하는 발현 벡터를 제공하는 단계;
혼합물로부터 뉴클레오티드 서열을 발현 벡터로 도입시키는 단계; 및
발현 단백질과 공동-발현되는 마커를 포함하는 융합 단백질의 존재 여부를 확인함으로써 발현 벡터에 의해 발현된 발현 단백질을 동정하는 단계를 포함하여 이루어진다.
바람직한 마커는 폴리히스티딘 태그이다. 하기 구체적인 실시예들은 폴리히스티딘 태그 마커 및 폴리히스티딘 태그 융합 단백질에 관한 것이다. 그러나, 검출될 수 있고, 발현 클론에서 단백질과 공동-발현될 수 있는 임의의 마커를 사용할 수 있다. 따라서, 본 발명은 폴리히스티딘 태그에 한정되지 않는다. 이 마커는 단지 실례일 뿐 기재된 본 발명의 보편성을 제한하는 것으로 받아들여서는 안된다.
상기한 바와 같이, 특히 유전자 라이브러리로부터 유도된 클론에서의 발현 단백질의 동정은 병원균에 대해 잠재적인 항원을 암호화하는 뉴클레오티드 서열의 동정을 촉진시킨다.
뉴클레오티드 서열의 혼합물은 조직 시료, 미생물, 세포 또는 핵산을 함유하는 어떤 성분과 같은 임의의 공급원으로부터 유도될 수 있다. 바람직하게는, 핵산은 게놈, 미토콘드리아, 재조합 또는 mRNA이다. DNA의 시료는 우선 예를 들면, 초 음파 또는 제한 효소 분해와 같은 효소 분해에 의해 DNA를 분해하는 어떤 방법으로 분해한다. 이와 달리, 뉴클레오티드 서열은 상기 DNA 서열의 일부의 PCR로부터 유도할 수 있다. 이러한 서열은 오픈 리딩 프레임(open reading frames: ORF)일 수 있다. 발현 벡터는 폴리히스티딘 태그를 포함하는 것이 바람직하다. 폴리히스티딘 태그는 상기와 같이 폴리히스티딘 태그를 포함하는 임의의 공급원으로부터 유도될 수 있다.
폴리히스티딘 태그는 pQE30, pQE31 및 pQE32(Qiagen Pty. Ltd. Australia)와 같은 표준 벡터로부터 유도될 수 있다. 이러한 벡터는 T5 프로모터, Lac 오퍼레이터 및 폴리히스티딘 태그 영역을 암호화할 수 있다. 이 영역은 뉴클레오티드 서열에 의해 암호화된 단백질을 발현할 수 있는 발현 벡터로 클로닝될 수 있다. 이와 달리, 폴리히스티딘 태그는 합성 제조될 수 있다.
바람직하게는 마커 또는 바람직하게는 폴리히스티딘 태그 영역이 진핵 세포 발현 벡터로 클로닝된다. 더 바람직하게는, 벡터는 pCI(Promega Corporation, Australia)이고, 바람직하게는 클론 pCI30, pCI31 및 pCI32를 생성한다.
이러한 일련의 벡터들은 모든 세 개의 리딩 프레임에서 단편들을 폴리히스티딘 태그 영역의 하류에 클로닝하게 한다. 이 예시된 클론에서 사이토메갈로바이러스(CMV) 즉시-초기 인헨서(enhancer)/프로모터, 키메라 인트론, 및 SV40 후기 폴리아데닐레이션 신호로 인해, 벡터는 정제된 플라스미드 DNA를 사용하는 유전자 면역화 및 세포 배양 시스템에서 진핵 세포 발현 벡터로 사용된다. T5 프로모터는 원핵세포에서 클로닝된 삽입물을 발현하게 한다. 이 벡터들의 구조는 중요한데, 그 이유는 이들이 재조합 단백질을 발현하는 다수의 클론들을 동정하기 위한 라이브러리를 선별할 수 있기 때문이다.
게놈 DNA를 분해한 것과 같은 혼합물에서의 뉴클레오티드 서열(들)은 당업자들에게 공지된 임의의 방법에 의해 도입되거나 발현 벡터로 도입될 수 있다. 발현 벡터는 숙주 세포에서 단백질을 발현하는데 사용될 수 있다.
바람직한 실시형태에서, 폴리히스티딘 태그 및 발현 단백질을 포함하는 폴리히스티딘 융합 단백질의 발현 단백질을 발현하기 위해서 발현 벡터는 숙주 세포에 유전자도입된다. 발현 벡터를 숙주 세포에 도입하면 게놈 또는 cDNA 라이브러리를 만들 수 있다.
숙주 세포는 발현 벡터를 수용할 수 있는 임의의 세포일 수 있다. 이 세포는 원핵세포인 것이 바람직하다. 대장균인 것이 가장 바람직하다. 단백질을 발현하는 발현 단백질(및 이어서 임의의 클론 또는 숙주 세포)의 동정은 폴리히스티딘 태그 융합 단백질 상의 폴리히스티딘 태그의 존재 여부에 의해 확인할 수 있다.
본 발명의 벡터는 폴리히스티딘 태그를 기초로 모든 발현 클론에 대한 일반적인 스크리닝을 할 수 있게 한다.
폴리히스티딘 태그는 폴리히스티딘 신호가 색원체 기질의 첨가에 의해 발현되는 것을 특징으로 하는 니켈 수지와 같은 탐침과 결합된 금속 킬레이트로 또는 항-폴리히스티딘 항체를 사용하여 동정할 수 있다.
재조합 폴리히스티딘 융합 단백질, 또는 단지 짧은 재조합 단백질을 생성하지 않는 클론에서, 암호화된 작은 폴리히스티딘 단백질은 숙주 세포 안으로 신속하 게 분해되고, 잔존하는 임의의 폴리히스티딘 단백질은 콜로니 스크리닝을 위해 사용되는 막에 매우 약하게 결합한다. 따라서, 비-생산적인 클론은 폴리히스티딘 콜로니 스크리닝에 부정적인 결과를 낳는 반면, 더 길게 폴리히스티딘 태그된 재조합 단백질을 생성하는 클론은 긍정적인 신호를 제공할 수 있다. 따라서, 일반적인 게놈 발현 라이브러리는 복잡성이 상당히 감소될 수 있으므로, 더 빠르고 더 효율적인 스크리닝 및 이어서 원하는 클론의 사용을 가능하게 한다.
이 방법의 다른 바람직한 실시형태에는 융합 단백질에서 발현되는 폴리히스티딘 태그를 사용하여 발현 단백질을 정제하는 단계가 포함된다.
폴리히스티딘 태그를 사용하여 발현 클론에 의해 발현된 발현 단백질을 동정한 후, 이 태그는 임의의 발현 단백질을 정제하기 위해 사용될 수 있다. 당업자에게 공지된 임의의 정제 방법을 사용할 수 있다. 항-폴리히스티딘 항체를 사용한 친화도 크로마토그래피에서 친화도 컬럼을 사용할 수 있다. 일반적으로, 폴리히스티딘 태그에 의해 동정된 발현 단백질은 폴리히스티딘 태그의 사용에 의존하는 임의의 방법을 사용하여 분리할 수 있다.
다른 실시형태는 상기 방법에 따라 동정된 정제된 재조합 단백질을 제공한다.
일단 단백질이 분리되면, 정제된 단백질의 형태로 백신 실험을 포함한 어떤 다수의 방법에 사용될 수 있다. 이 단백질은 잠재적 항원으로서 즉시 동정될 수 있다. 이것은 보호 항원이 되는 것이 바람직하다.
다른 실시형태는 상기 방법에 따라 동정된 재조합 단백질을 암호화하는 정제 된 뉴클레오티드 서열을 제공한다.
상기 폴리히스티딘 방법에 의해 동정된 단백질은 분리된 뉴클레오티드 서열, 바람직하게는 재조합 서열에 의해 발현된다. 단백질을 동정함으로써, 뉴클레오티드 서열을 포함하는 단백질을 발현하는 클론을 동정할 수 있다.
이러한 클론은 정제된 플라스미드 DNA를 제공하며, 특히, 플라스미드 DNA는 잠재적 보호 항원을 나타낼 수 있다.
본 발명의 다른 실시형태는 뉴클레오티드 서열에 의해 암호화된 발현 단백질을 동정하는데 사용하기 위해 마커, 바람직하게는 폴리히스티딘 태그를 포함하는 재조합 벡터 또는 발현 벡터를 제공한다.
발현 벡터는 발현 단백질의 발현을 생성하는 임의의 벡터일 수 있다. 플라스미드 또는 코스미드일 수 있다. 이것은 클론으로 도입되어 백신 접종 또는 동정 목적을 위한 단백질을 얻기 위한 목적으로 발현 단백질을 더 확대할 수 있다.
본 발명의 다른 형태는 발현 벡터를 포함하는 숙주를 제공하며, 상기 벡터는 뉴클레오티드 서열에 의해 암호화된 발현 단백질을 동정하는데 사용하기 위한 마커, 바람직하게는 폴리히스티딘 태그를 포함한다.
숙주 세포는 발현 벡터를 포함할 수 있는 어떤 수용 능력 있는 세포일 수 있다. 숙주 세포는 원핵세포 또는 진핵세포인 것이 바람직하다.
본 발명의 다른 실시형태는 뉴클레오티드 서열의 시료로부터 항원 단백질을 암호화하는 유전자 서열을 동정하는 방법을 제공하며, 상기 방법은:
마커, 바람직하게는 폴리히스티딘 태그를 포함하는 발현 벡터를 제공하는 단 계;
시료로부터 뉴클레오티드 서열을 발현 벡터로 도입시키는 단계;
뉴클레오티드 서열에 의해 번역된 발현 단백질과 공동-발현되는 마커를 포함하는 융합 단백질의 존재 여부를 확인함으로써 발현 벡터에 의해 발현된 항원 발현 단백질을 동정하는 단계;
항원 단백질을 동정하는 단계; 및
발현 벡터에 의해 암호화된 항원 단백질 유전자의 뉴클레오티드 서열을 바람직하게 확인하는 단계를 포함하여 이루어진다.
항원 단백질의 동정은 폴리히스티딘 태그를 가진 융합 단백질을 동정 및 바람직하게는 분리하고, 융합 단백질이 폴리히스티딘 태그에 의해 생성되지 않는 면역 반응을 유도할 수 있는지를 결정하는 것을 포함한다. 면역 반응은 ELISA 또는 항체/항원 반응을 수행하는 면역 동물로부터의 항혈청을 사용하는 표준 시험관 내 면역학적 실험에 의해 결정할 수 있다.
본 발명의 다른 실시형태는 뉴클레오티드 서열의 라이브러리를 스크리닝하는 방법을 제공하며, 상기 방법은:
뉴클레오티드 서열의 공급원을 제공하는 단계;
마커, 바람직하게는 폴리히스티딘 태그를 포함하는 발현 벡터를 제공하는 단계;
뉴클레오티드 서열을 발현 벡터로 도입함으로써 라이브러리를 만드는 단계;
뉴클레오티드 서열에 의해 번역된 발현 단백질과 공동-발현되는 마커를 포함 하는 융합 단백질의 존재 여부를 확인함으로써 발현 벡터에 의해 발현된 발현 단백질을 동정하는 단계; 및
발현 단백질 유전자의 뉴클레오티드 서열을 확인하는 단계를 포함한다.
다른 실시형태는 라이브러리에서 발현 클론을 동정하기 위해 스크리닝하는 방법을 제공하며, 상기 방법은:
뉴클레오티드 서열의 공급원을 제공하는 단계;
마커, 바람직하게는 폴리히스티딘 태그를 포함하는 발현 벡터를 제공하는 단계;
뉴클레오티드 서열을 발현 벡터로 도입시키는 단계;
발현 벡터를 숙주로 유전자도입하여 발현 라이브러리를 만드는 단계; 및
발현 단백질과 공동-발현되는 마커, 바람직하게는 폴리히스티딘 태그를 포함하는 융합 단백질의 발현을 검출하여 발현 클론의 위치를 확인하는 단계를 포함한다.
발현 클론에 의해 전사된 폴리히스티딘 태그를 가진 발현 단백질의 동정은 오픈 리딩 프레임(ORF)을 발현하는 클론(숙주 세포)들을 더 동정한다.
따라서, 이 방법은 뉴클레오티드 서열의 혼합물에서 ORF를 동정한다. 이는 잠재적으로 항원으로서 유용한 단백질을 암호화하는 유용한 뉴클레오티드 서열을 동정하는 과정을 효과적으로 가속화시킨다. 이것은 즉시 확대될 수 있는 클론을 신속하게 동정하여, 유전자 백신과 같은 어떤 용도를 위해 또는 재조합 단백질에 대한 항체를 개발하기 위해 충분한 뉴클레오티드 서열 또는 플라스미드 DNA 또는 재조합 단백질 시료를 제공한다.
본 발명의 다른 실시형태는 뉴클레오티드 서열의 시료에서, 질환의 치료 항원 단백질을 암호화하는 치료 항원 유전자 서열을 동정하는 방법을 제공하며, 상기 방법은:
마커를 포함하는 발현 벡터를 제공하는 단계;
시료로부터 뉴클레오티드 서열을 발현 벡터로 도입시키는 단계;
뉴클레오티드 서열에 의해 번역된 발현 단백질과 공동-발현되는 마커를 포함하는 융합 단백질의 존재 여부를 확인함으로써 발현 벡터에 의해 발현된 항원 발현 단백질을 동정하는 단계;
항원 발현 단백질을 발현하는 발현 벡터를 동물에게 접종시키는 단계;
동물을 질병으로 감염시키는 단계;
백신접종에 의해 유도된 치료적 효과를 제공하는 발현 벡터 및 발현 단백질을 동정하는 단계; 및
발현 벡터에 의해 암호화된 항원 발현 단백질의 유전자 서열을 확인하는 단계를 포함하여 이루어진다.
본 발명은 클론의 백신 가능성을 즉시 평가하기 위해, 뉴클레오티드 서열의 라이브러리를 스크리닝하고, DNA 백신 접종 실험에 동정된 클론을 사용하는 효과적인 방법을 제공한다는 점에서 유리하다. 백신 실험을 하기 위해 동정된 클론을 용이하게 사용하는 이러한 면은 현재 사용가능한 방법을 더 개선한다.
본 발명의 다른 바람직한 실시형태는, 마이코플라스마, 바람직하게는 마이코 플라스마 하이오뉴모니아의 폴리펩티드를 암호화하는 뉴클레오티드 서열에 대한 뉴클레오티드 서열의 라이브러리를 스크리닝하는 방법을 제공하며, 상기 방법은:
마이코플라스마 시료로부터 뉴클레오티드 서열의 공급원을 제공하는 단계;
마커, 바람직하게는 폴리히스티딘 태그를 포함하는 발현 벡터를 제공하는 단계;
뉴클레오티드 서열을 발현 벡터에 도입시키는 단계;
뉴클레오티드 서열에 의해 번역된 발현 단백질과 공동-발현되는 마커, 바람직하게는 폴리히스티딘 태그를 포함하는 융합 단백질의 존재 여부를 확인함으로써 발현 벡터에 의해 발현된 마이코플라스마 발현 단백질을 동정하는 단계; 및
마이코플라스마, 바람직하게는 마이코플라스마 하이오뉴모니아의 발현 단백질 유전자의 뉴클레오티드 서열을 확인하는 단계를 포함하여 이루어진다.
마이코플라스마의 시료로부터의 뉴클레오티드 서열의 공급원은 게놈, 미토콘드리아, 재조합 또는 mRNA 기원일 수 있다. 공급원이 게놈인 경우, 게놈 DNA는 당업자에게 공지된 임의의 방법에 의해 마이코플라스마로부터 분리될 수 있다.
마이코플라스마는 마이코플라스마 하이오뉴모니아인 것이 바람직하다. 폴리히스티딘 태그-마이코플라스마 융합 단백질의 동정 방법은 상기한 바와 같다.
바람직하게는, 뉴클레오티드 서열은 항원 단백질을 암호화한다. 따라서, 단백질이 면역 반응을 유도하는지를 확인하는 단계가 더 있다. 바람직하게는, 항원 단백질은 마이코플라스마 항원 단백질이다. 더 바람직하게는, 마이코플라스마 하이오뉴모니아 항원 단백질이다.
"면역 반응"이라는 용어는 일반적으로 미생물, 기생충, 이식조직, 단백질 또는 항원과 같은 외부 성분의 침입에 대한 특이적 항체 및/또는 세포독성 세포가 생성되는 면역계에 의해 개시된 선택적 반응을 의미한다.
"면역계"라는 용어는 감염으로부터 신체를 보호하기 위해 및 경우에 따라 재감염에 대해 오래 지속되는 특이적 면역을 제공하기 위해, 일반적으로 미생물, 기생충, 이식조직, 단백질 또는 항원과 같은 외부 성분의 침입에 대한 특이적 보호 반응을 개시할 수 있는 임의의 세포 또는 조직을 의미한다.
본 발명의 다른 실시형태는, 마이코플라스마, 바람직하게는 마이코플라스마 하이오뉴모니아의 폴리펩티드를 암호화하는 뉴클레오티드 서열, 돌연변이체, 유사체, 유도체 또는 기능적으로 활성인 이의 단편을 제공하며, 상기 뉴클레오티드 서열은 상기 방법에 의해 동정된다. 뉴클레오티드 서열은 도 1a 내지 42 중의 어느 하나에 따른 서열, 및 돌연변이체, 유사체, 유도체 또는 기능적으로 활성인 이의 단편을 포함하는 것이 바람직하다. 더 상세하게는, 이것은 SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:77, SEQ ID NO:79, SEQ ID NO:81 또는 SEQ ID NO:83 또는 돌연변이체, 유사체, 유도체 또는 기능적으로 활성인 이의 단편을 포함한다.
다른 실시형태에서, 하기 뉴클레오티드 서열을 포함하는 재조합 벡터, 돌연변이체, 유사체, 유도체 또는 기능적으로 활성인 이의 단편이 제공된다. 뉴클레오티드 서열은 도 1a 내지 42 중의 어느 하나에 따르는 서열, 돌연변이체, 유사체, 유도체 또는 기능적으로 활성인 이의 단편이 바람직하다. 더욱 구체적으로, SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:77, SEQ ID NO:79, SEQ ID NO:81 또는 SEQ ID NO:83 또는 돌연변이체, 유사체, 유도체 또는 기능적으로 활성인 이의 단편을 포함하여 이루어진다.
"돌연변이체, 유사체, 또는 유도체"라는 용어는 그 서열의 결손, 첨가 또는 치환을 포함할 수 있는 서열을 의미한다. 이러한 용어가 단백질과 관련되는 경우, 상기 변화는 단백질의 활성을 실질적으로 변화시키지 않는다. 변화된 핵산 분자와 관련되는 경우, 상기 변화는 단백질 암호화 영역의 리딩 프레임에 변화를 일으키지 않으며, 바람직하게는 변화가 없는 단백질을 암호화하고, 생물학적 기능을 약간 감 소시키거나 증가시킬 뿐이다.
"단편"이라는 용어는, 전체 길이보다 짧으나 전장 서열과 보합결합할 수 있고, 전장 서열의 일부인 아미노산 서열을 암호화할 수 있는 핵산 서열의 일부로서 인식되는 핵산 또는 아미노산 서열 일부를 의미한다.
유전 코드의 축퇴로 인해 동일하거나 기능적으로 동등한 아미노산 서열을 암호화하는 다른 핵산 서열도 본 발명의 범위에 포함된다. 뉴클레오티드 서열의 이러한 변형은, 동일하거나 기능적으로 동등한 유전자 산물을 얻는 다른 뉴클레오티드의 치환을 포함할 수 있다. 본 발명의 범위에는 또한 결손 및/또는 첨가가 일어난, 기능적으로 동등한 유전자 산물을 얻는 핵산 서열이 포함된다. 또한, 유전자 산물은, 기능적으로 활성인 산물을 생성하는 변화를 일으키는 서열의 아미노산 잔기가 결손, 첨가 또는 치환된 것을 포함할 수 있다.
다른 실시형태에서, 상기 재조합 벡터를 포함하는 숙주 세포가 제공된다. 숙주 세포는 재조합 벡터를 수용할 수 있는 어떤 세포가 가능하다. 숙주 세포는 원핵 세포가 바람직하고, 대장균이 더욱 바람직하다.
본 발명의 다른 실시형태에서, 상기 방법으로 동정된 폴리펩티드를 암호화하는 아미노산 서열이 제공된다. 폴리펩티드는 발현 벡터의 산물일 수 있으며, 또는 마커, 바람직하게는 폴리히스티딘 마커와 공동-발현된 단백질로서 동정된 발현 단백질이다. 아미노산 서열이 상기 방법으로 동정된 뉴클레오티드 서열로부터 번역되는 것이 바람직하다.
바람직한 실시형태에서, 이 아미노산 서열은 마이코플라스마, 바람직하게는 마이코플라스마 하이오뉴모니아의 폴리펩티드를 암호화한다. 더욱 바람직하게는 이 아미노산 서열은 도 1a 내지 42 중의 어느 하나에 따른 서열, 돌연변이체, 유사체, 유도체 또는 기능적으로 활성인 이의 단편을 포함하여 이루어진다. 더욱 구체적으로 SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO 62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO 74, SEQ ID NO: 76, SEQ ID NO:78, SEQ ID NO:80, SEQ ID NO:82 또는 SEQ ID NO:84 또는 돌연변이체, 유사체, 유도체 또는 기능적으로 활성인 이의 단편을 포함하여 이루어진다.
본 발명의 다른 실시형태에서, 상기와 같은 아미노산 서열, 돌연변이체, 유사체, 유도체 또는 기능적으로 활성인 이의 단편으로 암호화되는 폴리펩티드가 제공된다. 이 서열은 마이코플라스마, 바람직하게는 마이코플라스마 하이오뉴모니아의 폴리펩티드를 암호화하고, 상기 아미노산 서열은 상기 방법으로 동정되는 것이 바람직하다. 이 폴리펩티드는 도 1a 내지 42 중의 어느 하나에 따른 아미노산 서열, 돌연변이체, 유사체, 유도체 또는 기능적으로 활성인 이의 단편으로 암호화되는 것이 바람직하다. 더욱 구체적으로 SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO 62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO 74, SEQ ID NO: 76, SEQ ID NO:78, SEQ ID NO:80, SEQ ID NO:82 또는 SEQ ID NO:84 또는 돌연변이체, 유사체, 유도체 또는 기능적으로 활성인 이의 단편을 포함하여 이루어진다.
이 폴리펩티드는 당업자에게 어떤 공지된 방법으로 분리 및 정제될 수 있다. 분리 방법은 뉴클레오티드 서열 라이브러리로부터 발현 단백질 또는 발현 클론을 동정하기 위해 사용되었던 폴리히스티딘 태그를 사용하는 것이 바람직하다.
다른 실시형태에서, 상기한 바와 같은 폴리펩티드 또는 뉴클레오티드 서열을 포함하여 이루어지는 조성물이 제공된다. 이 조성물은 상기와 같은 하나 이상의 폴리펩티드 또는 뉴클레오티드 서열 및 약제학적으로 허용가능한 담체를 포함하여 이루어지는 약제학적 조성물일 수 있다. 이 조성물은 또한 상기한 하나 이상의 폴리펩티드 또는 뉴클레오티드 서열을 포함하여 이루어지는 백신 조성물일 수 있다. 폴리펩티드가 바람직하게는 마이코플라스마, 더욱 바람직하게는 마이코플라스마 하이오뉴모니아의 뉴클레오티드 서열 또는 항원 단백질인 이 백신 조성물은 면역 반응을 일으킬 수 있다.
본 발명의 다른 실시형태에서, 상기되거나 상기된 방법에 따라 동정된 폴리 펩티드에 대한 항체가 제공된다. 이 항체는 모노클로날 항체인 것이 바람직하다.
당해 기술 분야에서 상기 폴리펩티드의 에피토프에 대한 항체를 제조하기 위하여 사용가능한 다양한 방법은 공지되어 있다. 토끼, 마우스, 염소 등을 포함하며 이에 한정되지 않는 다양한 숙주 동물을, 폴리펩티드를 사용하여 면역화시킨 후 이들 항체를 제조하는데 사용할 수 있다. 숙주 종에 따라 면역 반응을 증가시키기 위하여 보강제를 사용할 수 있으며, 프로인트(Freunds)(완전 및 불완전)를 포함할 수 있으나 이에 한정되지 않는다. 모노클로날 항체는 시험관 내에서 세포주로 항체 분자를 연속 제조할 수 있는 기술을 사용하여 제조할 수 있다. 이는 히브리도마 기술(Kohler and Milstein, Nature 256, 495, (1975))을 포함할 수 있으나 이에 한정되지는 않는다. 폴리펩티드에 대한 항체는 다양한 조직, 체액 및 세포주에서 항원 폴리펩티드의 검출, 예를 들어 항원의 스크리닝 분석 및 폴리펩티드(바람직하게는 항원 폴리펩티드)의 친화 정제에 사용할 수 있다.
백신 조성물은 상기 뉴클레오티드 서열을 포함하는 정제된 플라스미드 DNA를 포함한다.
본 발명의 다른 실시형태에서 아미노산 서열에 의해 암호화되고 상기된 방법에 의해 동정되는 항원 폴리펩티드를 유효량으로 투여하는 것을 포함하는 감염 치료 방법이 제공된다. 감염은 마이코플라스마 감염이 바람직하다. 감염이 마이코플라스마 하이오뉴모니아 감염인 것이 더욱 바람직하다.
또한, 이 폴리펩티드는 도 1a 내지 42 중의 어느 하나에 따른 아미노산 서열, 돌연변이체, 유사체, 유도체 또는 기능적으로 활성인 이의 단편에 의해 암호화된 아미노산 서열로 암호화되는 것이 바람직하다. 더욱 구체적으로 이 서열은 SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:77, SEQ ID NO:79, SEQ ID NO:81 또는 SEQ ID NO:83 또는 돌연변이체, 유사체, 유도체 또는 기능적으로 활성인 이의 단편을 포함하여 이루어진다.
이 폴리펩티드는 도 1a 내지 42 중의 어느 하나에 따른 아미노산 서열, 돌연변이체, 유사체, 유도체 또는 기능적으로 활성인 이의 단편을 갖는 것이 또한 바람직하다. 더욱 구체적으로는, SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO 62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO 74, SEQ ID NO: 76, SEQ ID NO:78, SEQ ID NO:80, SEQ ID NO:82 또는 SEQ ID NO:84, 돌연변이체, 유사체, 유도체 또는 기능적으로 활성인 이의 단편을 포함하여 이루어진다.
본 발명의 다른 실시형태에서, 필요한 동물에 상기 방법에 의해 동정된 뉴클레오티드 서열을 포함하는 유효량의 DNA 분자를 투여하는 것을 포함하는 감염 치료 방법이 제공된다. 이 감염은 마이코플라스마 감염이 바람직하다. 이 감염은 마이코플라스마 하이오뉴모니아 감염인 것이 더욱 바람직하다.
이 뉴클레오티드 서열은 도 1a 내지 42 중의 어느 하나에 따른 서열, 돌연변이체, 유사체, 유도체 또는 기능적으로 활성인 이의 단편, 또는 더욱 구체적으로는 SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:77, SEQ ID NO:79, SEQ ID NO:81 또는 SEQ ID NO:83 또는 돌연변이체, 유사체, 유도체 또는 기능적으로 활성인 이의 단편이다.
DNA는 세포가 DNA를 포함할 수 있도록 하는 주사를 통하여 투여하거나, 국부적으로 적용할 수 있다. DNA를 피하 또는 근육 내에 피부층 속으로 주사하는 것이 바람직하다.
본 발명의 다른 실시형태에서, 상기된 방법에 의하여 동정된 폴리펩티드에 특이적인 항체를 유효량으로 투여하는 것을 포함하는 감염의 치료 방법이 제공된다.
이 감염은 마이코플라스마 감염이 바람직하다. 이 감염은 마이코플라스마 하이오뉴모니아 감염인 것이 더욱 바람직하다.
이 폴리펩티드 서열은 도 1a 내지 42 중의 어느 하나에 따른 아미노산 서열, 돌연변이체, 유사체, 유도체 또는 기능적으로 활성인 이의 단편, 또는 더욱 구체적으로는 SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO 62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO 74, SEQ ID NO: 76, SEQ ID NO:78, SEQ ID NO:80, SEQ ID NO:82 또는 SEQ ID NO:84 또는 돌연변이체, 유사체, 유도체 또는 기능적으로 활성인 이의 단편에 의하여 암호화된다.
이제 실시예 및 도면을 참조하여 본 발명을 더욱 상세히 설명한다. 그러나, 다음 상세한 설명은 설명을 위한 것으로, 이에 본 발명의 일반적인 사항이 제한되는 것은 아니다.
도 1a 내지 도 1b는 클론 pAD612로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:1) 및 아미노산 서열(SEQ ID NO:2)을 나타내는 도이다.
도 2a 내지 도 2b는 클론 pAD633으로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:3) 및 아미노산 서열(SEQ ID NO:4)을 나타내는 도이다.
도 3a 내지 도 3b는 클론 pAD639로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:5) 및 아미노산 서열(SEQ:ID NO:6)을 나타내는 도이다.
도 4는 클론 pAD640으로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:7) 및 아미노산 서열(SEQ ID NO:8)을 나타내는 도이다.
도 5a 내지 도 5b는 클론 pAD641 및 pAD1033으로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:9) 및 아미노산 서열(SEQ ID NO:10)을 나타내는 도이다.
도 6a 내지 도 6d는 클론 pAD653으로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:11) 및 아미노산 서열(SEQ ID NO:12)을 나타내는 도이다.
도 7a 내지 도 7b는 클론 pAD657 및 pAD964로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:13) 및 아미노산 서열(SEQ ID NO:14)을 나타내는 도이다.
도 8a 내지 도 8b는 클론 pAD659 및 pAD910으로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:15) 및 아미노산 서열(SEQ ID NO:16)을 나타내는 도이다.
도 9a 내지 도 9c는 클론 pAD662로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:17) 및 아미노산 서열(SEQ ID NO:18)을 나타내는 도이다.
도 10a 내지 도 10b는 클론 pAD681로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:19) 및 아미노산 서열(SEQ ID NO:20)을 나타내는 도이다.
도 11a 내지 도 11b는 클론 pAD700으로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:21) 및 아미노산 서열(SEQ ID NO:22)을 나타내는 도이다.
도 12는 클론 pAD711로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:23) 및 아미노산 서열(SEQ ID NO:24)을 나타내는 도이다.
도 13은 클론 pAD721로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:25) 및 아미노산 서열(SEQ ID NO:26)을 나타내는 도이다.
도 14a 내지 도 14b는 클론 pAD727로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:27) 및 아미노산 서열(SEQ ID NO:28)을 나타내는 도이다.
도 15a 내지 도 15d는 클론 pAD742로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:29) 및 아미노산 서열(SEQ ID NO:30)을 나타내는 도이다.
도 16a 내지 도 16c는 클론 pAD760으로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:31) 및 아미노산 서열(SEQ ID NO:32)을 나타내는 도이다.
도 17a 내지 도 17c는 클론 pAD774로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:33) 및 아미노산 서열(SEQ ID NO:34)을 나타내는 도이다.
도 18a 내지 도 18b는 클론 pAD784로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:35) 및 아미노산 서열(SEQ ID NO:36)을 나타내는 도이다.
도 19는 클론 pAD789로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:37) 및 아미노산 서열(SEQ ID NO:38)을 나타내는 도이다.
도 20a 내지 도 20c는 클론 pAD908, pAD981, pAD1013 및 pAD1049로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:39) 및 아미노산 서열(SEQ ID NO:40)을 나타내는 도이다.
도 21a 내지 도 21b는 클론 pAD913으로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:41) 및 아미노산 서열(SEQ ID NO:42)을 나타내는 도이다.
도 22는 클론 pAD920으로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:43) 및 아미노산 서열(SEQ ID NO:44)을 나타내는 도이다.
도 23a 내지 도 23b는 클론 pAD922로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:45) 및 아미노산 서열(SEQ ID NO:46)을 나타내는 도이다.
도 24는 클론 pAD923 및 pAD925로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:47) 및 아미노산 서열(SEQ ID NO:48)을 나타내는 도이다.
도 25a 내지 도 25b는 클론 pAD950으로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:49) 및 아미노산 서열(SEQ ID NO:50)을 나타내는 도이다.
도 26은 클론 pAD951로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:51) 및 아미노산 서열(SEQ ID NO:52)을 나타내는 도이다.
도 27은 클론 pAD977로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:53) 및 아미노산 서열(SEQ ID NO:54)을 나타내는 도이다.
도 28은 클론 pAD983으로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:55) 및 아미노산 서열(SEQ ID NO:56)을 나타내는 도이다.
도 29는 클론 pAD984로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:57) 및 아미노산 서열(SEQ ID NO:58)을 나타내는 도이다.
도 30은 클론 pAD994로 표시된 마이코플라스마 서열 30의 뉴클레오티드(SEQ ID NO:59) 및 아미노산 서열(SEQ ID NO:60) 을 나타내는 도이다.
도 31은 클론 pAD1005로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:61) 및 아미노산 서열(SEQ ID NO:62)을 나타내는 도이다.
도 32는 클론 pAD1016으로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:63) 및 아미노산 서열(SEQ ID NO:64)을 나타내는 도이다.
도 33은 클론 pAD1020으로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:65) 및 아미노산 서열(SEQ ID NO:66)을 나타내는 도이다.
도 34는 클론 pAD1027로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:67) 및 아미노산 서열(SEQ ID NO:68)을 나타내는 도이다.
도 35는 클론 pAD1037로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:69) 및 아미노산 서열(SEQ ID NO:70)을 나타내는 도이다.
도 36a 내지 도 36c는 클론 pAD1038로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:71) 및 아미노산 서열(SEQ ID NO:72)을 나타내는 도이다.
도 37a 내지 37b는 클론 pAD1040으로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:73) 및 아미노산 서열(SEQ ID NO:74)을 나타내는 도이다.
도 38은 클론 pAD702로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:75) 및 아미노산 서열(SEQ ID NO:76)을 나타내는 도이다.
도 39는 클론 pAD763으로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:77) 및 아미노산 서열(SEQ ID NO:78)을 나타내는 도이다.
도 40은 클론 pAD766으로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:79) 및 아미노산 서열(SEQ ID NO:80)을 나타내는 도이다.
도 41은 클론 pAD957로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:81) 및 아미노산 서열(SEQ ID NO:82)을 나타내는 도이다.
도 42는 클론 pAD996으로 표시된 마이코플라스마의 뉴클레오티드(SEQ ID NO:83) 및 아미노산 서열(SEQ ID NO:84)을 나타내는 도이다.
도면 기호의 설명
아미노산을 나타내기 위해 사용한 문자는 하기와 같다.
알라닌 A
아르기닌 R
아스파라긴 N
아스파르트산 D
시스테인 C
글루탐산 E
글루타민 Q
글리신 G
히스티딘 H
이소류신 I
류신 L
리신 K
메티오닌 M
페닐알라닌 F
프롤린 P
세린 S
트레오닌 T
트립토판 W
티로신 Y
발린 V
마이코플라스마 유전자 코드는 UGA(TGA)는 일반적인 정지 신호와는 다른 트립토판을 암호화하기 때문에 보통 유전자 코드와는 다르다. 도 1a 내지 42 에서 나타낸 추정 번역에서 TGA는 트립토판 잔기에 대한 코드로 생각한다.
실시예 1: pCI30, pCI31 및 pCI32 게놈 라이브러리 구성
마이코플라스마 하이오뉴모니아에서 분리된 게놈 DNA를 초음파 처리 또는 부분 제한 효소 분해를 통하여 적당한 크기의 단편으로 분해하였다. 그리고나서, DNA를 아가로오스 겔 상에 이동시켜서, 크기가 선택된 단편을 이 겔에서 잘라내어 회수하였다. 벡터 DNA(pCI30, pCI31 및 pCI32)를 새우 알칼리성 포스파타아제로 처리된 적당한 제한 효소(Sma I 또는 BamHI)로 분해하여 말단의 포스페이트를 제거한 후, 아가로오스 겔에 이동시켰다. 일직선 형태의 밴드를 잘라내어 DNA를 회수하였다. 게놈 DNA 단편과 절단 벡터 DNA를 1:1 내지 5:1의 몰비로 혼합하고, 표준 결찰 조건을 사용하여 결찰하였다. 결찰 혼합물을 사용하여 수용능력있는 대장균 세포를 형질전환시킨 후, 다수의 별개의 게놈 라이브러리를 얻었다.
실시예 2: 게놈 라이브러리의 스크리닝
게놈 라이브러리를 암피실린(100㎍/ml) 함유 루리아-베르토니(Luria-Bertoni; LB) 브로스 아가 상에 도포하고 밤새 37℃로 성장시켰다. 건조된 멸균 니트로셀룰로오스 막을 콜로니 상부에 위치시키고, 이어서 즉시 이를 제거하여 암피실린 및 IPTG(1mM) 함유 LB 플레이트 상에 콜로니 쪽을 위로하여 위치시키고, 4시간동안 37℃에서 배양시킴으로써 이 플레이트의 필터 리프트 레플리카(filter lift replicas)를 만들었다. 그리고나서, 막을 표준 방법으로 처리하여 박테리아를 용해시키고, 막을 중화시키고, 단백질을 막에 결합시켰다. 이어서, 건조막을 항-폴리히스티딘 항체 또는 결합된 니켈 수지를 사용하여 조사하고, 색원체 기질을 첨가하여 폴리히스티딘 신호를 발현시켰다. 발현된 막을 원래의 플레이트에 다시 위치시키고, 양성 콜로니를 암피실린을 보충한 풍부한 성장 배지를 함유하는 96조, 깊은 조 플레이트에 놓았다. 이어서, 클론을 37℃에서 성장시켰다. 이러한 플레이트의 레플리카를 얻어 장기간 저장을 위하여 -70℃로 유지시켰다.
실시예 3: 선택된 클론의 서열 분석
각 라이브러리로부터 폴리히스티딘 양성 클론의 집합체를 선택하였다. 플라스미드 DNA를 제조하고, 벡터에 삽입된 부위의 바로 상류 영역과 상동인 프라이머를 사용한 자동화 디데옥시 서열확인법에 의해 삽입된 단편으로부터의 DNA 서열 정보를 얻었다. 얻어진 서열 데이터를 공개적으로 이용가능한 진뱅크(GenBank) 데이터베이스와 비교하였다. 본 출원인의 양성 서열 및 데이터베이스 엔트리 간의 상동 관계를 검토하였으며, 많은 경우에 있어 이러한 정보를 통해 클로닝된 유전자 단편의 가능한 기능 중 몇가지를 알게 되었다. 이러한 상동관계에 대한 정보에 기초하여, 마이코플라스마 하이오뉴모니아 감염동안 숙주의 면역계에 쉽게 접근가능하거나 다른 이유로 어느 수준의 보호를 제공할 것으로 생각되는 단백질을 암호화하는 유전자를 나타낼 것으로 보이는 양성 클론의 하부 그룹을 선택하였다. 이러한 선택된 양성 클론은 가능성이 있는 보호 항원을 암호화한다.
추가 연구를 위하여 선택된 클론 중 일부는 동일 유전자의 다른 부분을 나타낸다.
실시예 4: 가능성이 있는 보호 항원의 스크리닝
동정된 유전자의 치료 적용을 조사하기 위하여 일련의 동물 실험을 행하였다. 모든 실험은 유사한 프로토콜을 따랐다. M. 하이오뉴모니아가 없는 돼지 떼로부터의 돼지를 6주령에서 시작하여 2주 간격으로 3회 백신접종하였다. 500㎍의 플라스미드 DNA를 균등하게 둘로 나누어 2번 주사기가 설치된 바이오젝터 2000(Biojector 2000) 불필요 주입장치를 사용하여, 각 귓등의 기부조직에 하나씩 백신접종하였다. 3차 백신접종하고 1-2 주 후에, 활성 M. 하이오뉴모니아 감염된 돼지에서 유래한 0.45μM의 여과된 폐 균등액 5ml 투여량을 기관내 주입하여 돼지를 감염시켰다. 감염 3-4주 후에 돼지를 안락사시키고, 폐를 분리하여 폐렴 병변을 평가하였다. 폐렴 병변은 영향을 받은 폐엽(lung lobe)의 수를 세어 병에 걸린 각 폐엽의 퍼센트를 측정하여 평가하였다. 이러한 평가 시스템은 질병 상태에 대한 두 가지 기준, 엽 스코어(lobe score) 및 병변 스코어를 제공한다. 각 실험에 서, 각 그룹의 평균 결과를 나타낸다. 양성 치료 효과를 가졌던 클론 그룹의 실험 결과를 나타낸다. 클론의 다른 그룹은 양성 치료 효과를 나타내지 않았으며, 이러한 결과는 나타내지 않는다.
실험 1
클론 pA612-789를 포함한 클론 그룹으로 백신 접종
처리
엽 스코어
병변 스코어
백신 비접종, 비감염 0 0
백신 비접종, 감염 4.4 120
백신 접종, 감염 3.25 72.5
클론 pAD612-789를 함유하는 백신은 치료 효과를 나타냈다. 백신접종된 돼지의 엽 스코어는 대조구보다 26% 낮았고, 병변 스코어는 40% 낮았다.
실험 2
두가지 다른 클론 그룹을 백신으로 실험하였다.
그룹 1: pAD's 662, 774, 784, 922 및 964
그룹 2: pAD's 612, 633, 639, 640, 641, 653, 657, 659, 681, 700, 711, 721, 727, 742, 760, 789, 908, 910, 911, 913, 920, 923, 925, 950, 951, 966, 967, 977, 981, 983, 984, 994, 1001, 1005, 1013, 1016, 1020, 1027, 1033, 1037, 1038, 1040 및 1049.
처리
엽 스코어
병변 스코어
백신 비접종, 비감염 0 0
벡터 백신 접종, 감염 3.4 67
그룹 1 백신 접종, 감염 1.6 38
그룹 2 백신 접종, 감염 2.2 51
실험 2에서 유도된 질병의 총 심각도는 이보다 약하게 감염된 실험 1보다 낮았다. 클론의 두 그룹 모두 치료 효과를 나타냈다.
그룹 1의 백신은 엽 스코어를 53% 감소시켰고, 병변 스코어를 43% 감소시켰다. 그룹 2의 백신은, 빈 벡터 플라스미드 DNA를 사용하여 백신 접종한 그룹과 비교하여 엽 스코어를 35% 감소시켰고, 병변 스코어를 24% 감소시켰다.
실험 3
그룹 1: 실험 2의 그룹 1과 동일한 클론
바이오젝터에 대하여 설명한 바와 같은 표준 방법으로 또는 유전자총(genegun)을 사용하여 DNA를 전달하였다. 유전자 총으로 전달하기 위하여 돼지 각각에 1.6 미크론의 금 입자를 사용하여, 3회의 각 백신 접종 시점에서 각각 1.25㎍ DNA씩 4개로 접종하였다. 백신 접종은 각 귀의 뒤와 각 뒷다리 안쪽에 실시하였다. 전달 압력은 500psi였다.
처리
엽 스코어
병변 스코어
백신 비접종, 비감염 0 0
벡터 백신 접종, 감염 4.2 109
그룹 1 바이오젝터 백신 접종, 감염 2.5 67
그룹 1 유전자총 백신 접종, 감염 2.2 48.5
이 실험을 통하여, 노출(naked) DNA로 전달되는 경우에 그룹 1 중 5개 클론이 치료 효과를 갖는다는 것이 다시 증명되었다. 바이오젝터 전달된 백신은 엽 스코어를 40% 감소시켰으며, 병변 스코어를 39% 감소시켰다. 유전자총에 의하여 전달된 클론의 동일한 수집물은 엽 스코어를 48% 감소시켰고, 병변 스코어를 56% 감소시켰다.
실험 4
실험 2에 사용된 클론의 다른 조합물을 이 실험에 사용하였다.
그룹 3: pAD's 653, 711, 727, 920, 951, 및 965
그룹 4: pAD's 612, 639, 640, 1005, 1020, 및 1038
그룹 5: pAD's 742, 760, 923, 925, 994, 984, 및 1037
이전 실험에 사용되지 않았던 다른 5개 클론의 그룹을 또한 포함시켰다.
그룹 6: pAD's 702, 763, 766, 957, 및 996
처리
엽 스코어
병변 스코어
백신 비접종, 비감염 0 0
벡터 백신 접종, 감염 5.0 106
그룹 3 백신 접종, 감염 2.8 54
그룹 3 유전자 총 백신접종, 감염 2.6 87
그룹 4 백신접종, 감염 3.0 79
그룹 5 백신접종, 감염 3.6 74
그룹 6 백신접종, 감염 2.75 42.5
이들 클론 그룹은 모두 폐렴 병변의 심각도를 감소시킨다는 점에서 치료 효과를 가졌다. 그룹 3 클론은 엽 스코어를 바이오젝터로 전달되는 경우에 44% 감소시켰고, 유전자총으로 전달되는 경우에 48% 감소시켰으며, 병변 스코어를 바이오젝터로 전달되는 경우에 49%, 유전자 총으로 전달되는 경우에 18% 감소시켰다. 다른 3가지 실험백신은 바이오젝터로만 전달하였다. 그룹 4의 백신은 엽 스코어를 40%, 병변 스코어를 25% 감소시켰다. 그룹 5의 백신은 엽 스코어를 28%, 병변 스코어를 30% 감소시켰다. 그룹 6의 백신은 엽 스코어를 45%, 병변 스코어를 60% 감소시켰다.
실험 5
다음 백신을 실험 3에서 설명한 바와 같은 방식으로 유전자총으로 전달하였다.
처리 엽 스코어 병변 스코어
백신 비접종, 비감염 0 0
벡터 백신 접종, 감염 4.6 163
pAD662 1.0 23
pAD784 3.4 134
pAD922 4.6 124
pAD964 1.2 17
이 실험에서 치료 효능에 대해 시험한 네개의 클론은, 보다 큰 5개의 클론 그룹의 일부로서 이전의 실험 2 및 3에서 시험한 그룹 1 클론에서 유래한다. 클론 pAD662는 엽 스코어를 78% 감소시키고, 병변 스코어를 86% 감소시켰다. 클론 pAD964는 엽 스코어를 74% 감소시키고, 병변 스코어를 90% 감소시켰다. 다른 클론은 치료 효과가 거의 없었으며, 벡터 대조구에서 나타난 것과 유사한 결과를 나타내었다.
이 실험 및 이전 실험을 통하여, 약술된 방법을 사용하여 개별적으로 전달된 유전자 백신으로서 또는 더 큰 클론 그룹의 성분으로서 치료 효과를 갖는 클로닝된 유전자를 동정할 수 있음이 증명된다.
실험 6
클론 pAD662 및 pAD964로 암호화된 재조합 단백질을 분리하고, 친화도 크로마토그래피를 위해 폴리히스티딘 서열을 사용하여 정제하였다. 재조합 단백질 용액을 조합하여, 인터버트 인터네셔널 BV제 포타솔(Fortasol) 아쥬반트 중에 조성하였다. 돼지를 2주 간격으로 3회 백신접종한 후 감염시키고, 폐 병변을 이전 실험에서와 유사한 방식으로 스코어화하였다. 백신의 각 투여량에는 각 항원이 200 마이크로그람 존재하였다.
처리 엽 스코어 병변 스코어
백신 비접종, 비감염 0 0
백신 비접종, 감염 6.4 158
pAD662 및 pAD964 단백질 2.2 40
재조합 단백질에 의한 치료 효과는 명백하였다. 시험 백신 그룹은 엽 스코어를 66% 감소시키고, 병변 스코어를 75% 감소시켰다.
이 실험을 통하여, 우선 단백질 발현을 위해 클론을 스크리닝한 후, 유전자 백신 접종하는 것을 포함하는 약술된 방법을 사용하여 동정된 항원은, 재조합 단백질에 기초한 백신으로서 사용되는 경우에도 효과적일 수 있음이 증명된다.
실험 5
다음 백신을 실험 3에서 설명한 바와 같은 방식으로 유전자총으로 전달하였다.
처리 엽 스코어 병변 스코어
백신 비접종, 비감염 0 0
벡터 백신 접종, 감염 4.6 163
pAD662 1.0 23
pAD784 3.4 134
pAD922 4.6 124
pAD964 1.2 17
이 실험에서 치료 효능에 대해 시험한 네개의 클론은, 보다 큰 5개의 클론 그룹의 일부로서 이전의 실험 2 및 3에서 시험한 그룹 1 클론에서 유래한다. 클론 pAD662는 엽 스코어를 78% 감소시키고, 병변 스코어를 86% 감소시켰다. 클론 pAD964는 엽 스코어를 74% 감소시키고, 병변 스코어를 90% 감소시켰다. 다른 클론은 치료 효과가 거의 없었으며, 벡터 대조구에서 나타난 것과 유사한 결과를 나타내었다.
이 실험 및 이전 실험을 통하여, 약술된 방법을 사용하여 개별적으로 전달된 유전자 백신으로서 또는 더 큰 클론 그룹의 성분으로서 치료 효과를 갖는 클로닝된 유전자를 동정할 수 있음이 증명된다.
실험 6
클론 pAD662 및 pAD964로 암호화된 재조합 단백질을 분리하고, 친화도 크로마토그래피를 위해 폴리히스티딘 서열을 사용하여 정제하였다. 재조합 단백질 용액을 조합하여, 인터버트 인터네셔널 BV제 포타솔(Fortasol) 아쥬반트 중에 조성하였다. 돼지를 2주 간격으로 3회 백신접종한 후 감염시키고, 폐 병변을 이전 실험에서와 유사한 방식으로 스코어화하였다. 백신의 각 투여량에는 각 항원이 200 마이크로그람 존재하였다.
처리 엽 스코어 병변 스코어
백신 비접종, 비감염 0 0
백신 비접종, 감염 6.4 158
pAD662 및 pAD964 단백질 2.2 40
재조합 단백질에 의한 치료 효과는 명백하였다. 시험 백신 그룹은 엽 스코어를 66% 감소시키고, 병변 스코어를 75% 감소시켰다.
이 실험을 통하여, 우선 단백질 발현을 위해 클론을 스크리닝한 후, 유전자 백신 접종하는 것을 포함하는 약술된 방법을 사용하여 동정된 항원은, 재조합 단백질에 기초한 백신으로서 사용되는 경우에도 효과적일 수 있음이 증명된다.
이러한 종류의 실험을 통하여, 백신 비접종 또는 빈 벡터 백신 접종된 돼지와 비교하여, 본 특허에 상세히 설명한 클론된 유전자 수집물은, 재조합 플라스미드의 다양한 조합물로 백신 접종된 그룹에서 폐 병변의 심각도를 낮춤으로써 치료 효과를 가질 수 있다는 것이 증명된다. 이러한 치료 효과의 증명에 기초하여, 본 발명에서는 42가지 유전자 수집물을 청구한다.
실시예 5: 완전한 유전자를 회수하기 위한 게놈 라이브러리의 스크리닝
실시예 4에 기재된 클론은 일부 유전자 서열만을 포함한다. 완전한 유전자의 뉴클레오티드 서열을 동정하는 것이 바람직한데, 이들이 백신 설계에 유용할 추가의 에피토프를 암호화할 것으로 생각되기 때문이다. 실시예 4의 클론으로 나타낸 유전자의 완전한 암호화 영역을, 두 게놈 라이브러리를 스크리닝하여 회수하였다. 제한 효소 EcoRI 및 BgIII로 분해시켜 만든 단편을 EcoRI 및 BamHI로 각각 분해된 pUC18 벡터에 결찰시킴으로써 게놈 라이브러리를 구성하였다. 결찰된 생성물을 XL2-BlueMRF' 수용능력있는 세포(Stratagene)에 결찰 혼합하여 형질전환시키고, 100㎍/ml의 암피실린을 함유하는 루리아-베르토니 아가 플레이트 상에 도포하여 회수시켰다. 풍부한 성장 배지를 함유하는 96조 플레이트에 콜로니를 넣고, 밤새 성장시킨 후 각각에 대하여 플라스미드 DNA를 제조하였다. 각각으로부터의 플라스미드 DNA를 변성시켜 나이론막에 찍었다. 이어서, 대표적인 막을 실시예 4에 기재된 각 클론에 존재하는 삽입된 DNA로부터 얻은 디고시제닌(digoxigenin) 표지된 PCR 산물로 조사하였다. 제한효소 분해, 유전자 특이적 프라이머를 사용하는 PCR 및 뉴클레오티드 서열확인을 통하여 보합결합된 클론을 동정 및 분석하였다. 얻어진 유전자 서열은 도 1a 내지 42에 상세히 나타낸다. 다수의 이러한 서열은 유전자의 완전한 암호화 서열을 나타내지만, 많은 유전자들은 일부 서열만으로 이용가능하다.
마지막으로, 본 명세서의 정신을 벗어나지 않는 한 다양한 다른 변경 및/또는 변화가 가능한 것으로 이해해야 한다.
<110> COMMONWEALTH SCIENTIFIC AND INDUSTRIAL RESEARCH ORGANISATION
<120> METHODS OF IDENTIFYING ANTIGEN GENE SEQUENCES
<130> FPA05595
<150> AU PP7273
<151> 1998-11-20
<160> 84
<170> KOPATIN 1.5
<210> 1
<211> 1125
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD612
<400> 1
atggcaaaac aagattttta taaaattctg ggagttgaaa aatcagcatc actaacagaa 60
ataaaaaaag cttatcgaaa tttagtaaat atttatcatc ctgataaaaa tacaaaaaaa 120
tcagctgaag aacaaaaaca agctgaggcc aaatttaaag aaatccagga agcctacgaa 180
attttatctg atgaaacaaa gcgaaaacag tacgataaat tcggtcatgc cgcttttgat 240
cagcaatttg gtggtgggtc tagtggcttt tcaggatttg attttggcga tattttttca 300
agttttacct ctggttttgg ttttggcggc tcacaagaac aaaaatatag tcgtccttta 360
aagggcgaaa attttcaagc taaaatttat atcagtttta tcgagtcaat tctcggaaaa 420
gaaatctccc agaaattaac aaaatacgat caatgtgata actgtaaggg ttcaggcgct 480
aattcttctt ctgatattac aacttgctat aattgtcaag gtcggggaat gcaaactgag 540
gtcttaaata tcccgggatt tggtcgggtt cagaacaaaa caacttgttc agtttgttta 600
ggttccggga aaaacattac aaaaattgca aagaagtgcc atggaaaaac tatagttgag 660
acaaaagagg aagtaactat taaaattccg gccggaatcc aggatggaat gtttatccgc 720
gtggccggat ttggtggacc gggacacaaa ggcgggcctt ctggagatct tcatcttgag 780
attaatgttc gtcagcataa acattttact agatccggaa atgatattca tgtgaatatg 840
ccagtttcaa taattgatat tatcaaccaa aatactgtcg aagttcccaa cccaaccggt 900
ttgaaaaaag ttagacttta tgattattat aaatccggtc caattgttaa tgttcttcct 960
gctggggctc ctgatccaaa aaatccaaga attattggcg atctcaaggt tcatttaatt 1020
ttttatatcc ccgaatttag tccccgtcaa aaagatgagc tcaaccaggt ttttgctcaa 1080
atcaatgata aaacaaaggc aaaatgacta aaagaatttc aataa 1125
<210> 2
<211> 368
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD612
<400> 2
Met Ala Lys Gln Asp Phe Tyr Lys Ile Leu Gly Val Glu Lys Ser Ala
1 5 10 15
Ser Leu Thr Glu Ile Lys Lys Ala Tyr Arg Asn Leu Val Asn Ile Tyr
20 25 30
His Pro Asp Lys Asn Thr Lys Lys Ser Ala Glu Glu Gln Lys Gln Ala
35 40 45
Glu Ala Lys Phe Lys Glu Ile Gln Glu Ala Tyr Glu Ile Leu Ser Asp
50 55 60
Glu Thr Lys Arg Lys Gln Tyr Asp Lys Phe Gly His Ala Ala Phe Asp
65 70 75 80
Gln Gln Phe Gly Gly Gly Ser Ser Gly Phe Ser Gly Phe Asp Phe Gly
85 90 95
Asp Ile Phe Ser Ser Phe Thr Ser Gly Phe Gly Phe Gly Gly Ser Gln
100 105 110
Glu Gln Lys Tyr Ser Arg Pro Leu Lys Gly Glu Asn Phe Gln Ala Lys
115 120 125
Ile Tyr Ile Ser Phe Ile Glu Ser Ile Leu Gly Lys Glu Ile Ser Gln
130 135 140
Lys Leu Thr Lys Tyr Asp Gln Cys Asp Asn Cys Lys Gly Ser Gly Ala
145 150 155 160
Asn Ser Ser Ser Asp Ile Thr Thr Cys Tyr Asn Cys Gln Gly Arg Gly
165 170 175
Met Gln Thr Glu Val Leu Asn Ile Pro Gly Phe Gly Arg Val Gln Asn
180 185 190
Lys Thr Thr Cys Ser Val Cys Leu Gly Ser Gly Lys Asn Ile Thr Lys
195 200 205
Ile Ala Lys Lys Cys His Gly Lys Thr Ile Val Glu Thr Lys Glu Glu
210 215 220
Val Thr Ile Lys Ile Pro Ala Gly Ile Gln Asp Gly Met Phe Ile Arg
225 230 235 240
Val Ala Gly Phe Gly Gly Pro Gly His Lys Gly Gly Pro Ser Gly Asp
245 250 255
Leu His Leu Glu Ile Asn Val Arg Gln His Lys His Phe Thr Arg Ser
260 265 270
Gly Asn Asp Ile His Val Asn Met Pro Val Ser Ile Ile Asp Ile Ile
275 280 285
Asn Gln Asn Thr Val Glu Val Pro Asn Pro Thr Gly Leu Lys Lys Val
290 295 300
Arg Leu Tyr Asp Tyr Tyr Lys Ser Gly Pro Ile Val Asn Val Leu Pro
305 310 315 320
Ala Gly Ala Pro Asp Pro Lys Asn Pro Arg Ile Ile Gly Asp Leu Lys
325 330 335
Val His Leu Ile Phe Tyr Ile Pro Glu Phe Ser Pro Arg Gln Lys Asp
340 345 350
Glu Leu Asn Gln Val Phe Ala Gln Ile Asn Asp Lys Thr Lys Ala Lys
355 360 365
<210> 3
<211> 819
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD633
<400> 3
atgataaaag tttccgatgt ttgctttagt tatacaaaca acatggacca gcttgtgctg 60
aaaaatatta atgttgtttt tgaaaaaggt aaatattatg caattctagg gcataatggt 120
tcaggaaaat caacgttttc taagattctt tcaggaattt ttaaacctca aaaaggtagt 180
attgaagttg atggagtttt actaaataag gaaaatttaa cgaaaattag gaaaaaaatt 240
ggtataattt ttcaaaaccc agataatcaa tttgttgggg caacggttga agatgacatc 300
gctttcagtt tggaaaacat taatgaggat ccaaaaaaaa tgagtcaaat aatcgcaaat 360
ttagctgcaa aagtgcaaat ggagtcatat ttagaccgtg agccacaatt tttatctggg 420
ggccaaaagc aaaaagtagc aattgcatca gttttagcac taaatcctga gattataatt 480
tttgatgaaa taacttcaat gcttgatccc agaggtaaat atgatgttgt taaaattctt 540
gatgatctaa gaaaagataa aacaaaaact ttaatttcaa tcacccacaa tatgaatgaa 600
gcaattttag ctgatgaaat tattgttttt gcaaatgggg gaattatcgc tcagggggat 660
ccaaaattaa ttttaaatga taaaaatatc atcgaaaaag cgaaaattga ctccccattt 720
atctataaaa tttccagcgc acttaaatta gttagtccaa cttatgacga aaatgaattg 780
ctagagcaac tatgaaaatt aaagcaaaaa acatcgtaa 819
<210> 4
<211> 272
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD633
<400> 4
Met Ile Lys Val Ser Asp Val Cys Phe Ser Tyr Thr Asn Asn Met Asp
1 5 10 15
Gln Leu Val Leu Lys Asn Ile Asn Val Val Phe Glu Lys Gly Lys Tyr
20 25 30
Tyr Ala Ile Leu Gly His Asn Gly Ser Gly Lys Ser Thr Phe Ser Lys
35 40 45
Ile Leu Ser Gly Ile Phe Lys Pro Gln Lys Gly Ser Ile Glu Val Asp
50 55 60
Gly Val Leu Leu Asn Lys Glu Asn Leu Thr Lys Ile Arg Lys Lys Ile
65 70 75 80
Gly Ile Ile Phe Gln Asn Pro Asp Asn Gln Phe Val Gly Ala Thr Val
85 90 95
Glu Asp Asp Ile Ala Phe Ser Leu Glu Asn Ile Asn Glu Asp Pro Lys
100 105 110
Lys Met Ser Gln Ile Ile Ala Asn Leu Ala Ala Lys Val Gln Met Glu
115 120 125
Ser Tyr Leu Asp Arg Glu Pro Gln Phe Leu Ser Gly Gly Gln Lys Gln
130 135 140
Lys Val Ala Ile Ala Ser Val Leu Ala Leu Asn Pro Glu Ile Ile Ile
145 150 155 160
Phe Asp Glu Ile Thr Ser Met Leu Asp Pro Arg Gly Lys Tyr Asp Val
165 170 175
Val Lys Ile Leu Asp Asp Leu Arg Lys Asp Lys Thr Lys Thr Leu Ile
180 185 190
Ser Ile Thr His Asn Met Asn Glu Ala Ile Leu Ala Asp Glu Ile Ile
195 200 205
Val Phe Ala Asn Gly Gly Ile Ile Ala Gln Gly Asp Pro Lys Leu Ile
210 215 220
Leu Asn Asp Lys Asn Ile Ile Glu Lys Ala Lys Ile Asp Ser Pro Phe
225 230 235 240
Ile Tyr Lys Ile Ser Ser Ala Leu Lys Leu Val Ser Pro Thr Tyr Asp
245 250 255
Glu Asn Glu Leu Leu Glu Gln Leu Trp Lys Leu Lys Gln Lys Thr Ser
260 265 270
<210> 5
<211> 609
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD639
<400> 5
atgtttagtc aaactattta taaatgaaaa agcgaaaatc tcgaaagagt ggtcgtccct 60
gaaaaaggac tttcttgcga atataacggt ctttttagca taagaactgg caaaagtttg 120
tacgggctgc tacaaaattt agataatgat tattttattg cttacctaag atcaagtgtg 180
cttatcttta cctcttccgc atcatccgct ttagtaagag caaagtctta ttgcgaaaac 240
gatttttgat tgcataaaaa taatttttta gtcggcctta tcgtctttag tgccggaatt 300
tttaaaataa tggatggtag atgagaaaat acctatcttg ttaaatcagg ggatggtttt 360
aaccggtttt tacaagaact aaaaagcaaa aaacactata aattagaatg ttttttgctt 420
tcaaacttat tttttgtcag cctgagtcta actaatcata tcagaagtct agcccatcca 480
gatttaaata attcaactat ttatttaaat gaattatgcc ttgatgatct tagtcaaaaa 540
gaaactttag ctctaaaaag tcttggaaat tatgattttg acgatcaaga aaaggaactt 600
ttagagatc 609
<210> 6
<211> 203
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD639
<400> 6
Met Phe Ser Gln Thr Ile Tyr Lys Trp Lys Ser Glu Asn Leu Glu Arg
1 5 10 15
Val Val Val Pro Glu Lys Gly Leu Ser Cys Glu Tyr Asn Gly Leu Phe
20 25 30
Ser Ile Arg Thr Gly Lys Ser Leu Tyr Gly Leu Leu Gln Asn Leu Asp
35 40 45
Asn Asp Tyr Phe Ile Ala Tyr Leu Arg Ser Ser Val Leu Ile Phe Thr
50 55 60
Ser Ser Ala Ser Ser Ala Leu Val Arg Ala Lys Ser Tyr Cys Glu Asn
65 70 75 80
Asp Phe Trp Leu His Lys Asn Asn Phe Leu Val Gly Leu Ile Val Phe
85 90 95
Ser Ala Gly Ile Phe Lys Ile Met Asp Gly Arg Trp Glu Asn Thr Tyr
100 105 110
Leu Val Lys Ser Gly Asp Gly Phe Asn Arg Phe Leu Gln Glu Leu Lys
115 120 125
Ser Lys Lys His Tyr Lys Leu Glu Cys Phe Leu Leu Ser Asn Leu Phe
130 135 140
Phe Val Ser Leu Ser Leu Thr Asn His Ile Arg Ser Leu Ala His Pro
145 150 155 160
Asp Leu Asn Asn Ser Thr Ile Tyr Leu Asn Glu Leu Cys Leu Asp Asp
165 170 175
Leu Ser Gln Lys Glu Thr Leu Ala Leu Lys Ser Leu Gly Asn Tyr Asp
180 185 190
Phe Asp Asp Gln Glu Lys Glu Leu Leu Glu Ile
195 200
<210> 7
<211> 471
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD640
<400> 7
gaggtaagca cgattcccgg acgaggcgat attaaactaa caggttcgct taaggatgta 60
atgcaagaat cagcccggat tgccctttct tatgttcagt caaaggccaa ggattttggg 120
attaattttg attttgaaaa cactttaatt catattcatg tacccgaagg agcaattcca 180
aaagatgggc catcagcagg gataactttt gcaacagcaa taatttcagc cctctcgcaa 240
aagccggtct cacataatat tgcaatgaca ggggagataa ccttgcgcgg gaaggtttta 300
gcaatcggcg gactaaaaga aaagacgatg ggggcctatt taaatgggat taaaattatt 360
tttattccca aggcgaacga gaaaaattta gtcgatattc cgcaggaagt aaaagacgtt 420
atccagttta ttcccgttga tacttatcaa ccaatttatg attttatttt t 471
<210> 8
<211> 157
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD640
<400> 8
Glu Val Ser Thr Ile Pro Gly Arg Gly Asp Ile Lys Leu Thr Gly Ser
1 5 10 15
Leu Lys Asp Val Met Gln Glu Ser Ala Arg Ile Ala Leu Ser Tyr Val
20 25 30
Gln Ser Lys Ala Lys Asp Phe Gly Ile Asn Phe Asp Phe Glu Asn Thr
35 40 45
Leu Ile His Ile His Val Pro Glu Gly Ala Ile Pro Lys Asp Gly Pro
50 55 60
Ser Ala Gly Ile Thr Phe Ala Thr Ala Ile Ile Ser Ala Leu Ser Gln
65 70 75 80
Lys Pro Val Ser His Asn Ile Ala Met Thr Gly Glu Ile Thr Leu Arg
85 90 95
Gly Lys Val Leu Ala Ile Gly Gly Leu Lys Glu Lys Thr Met Gly Ala
100 105 110
Tyr Leu Asn Gly Ile Lys Ile Ile Phe Ile Pro Lys Ala Asn Glu Lys
115 120 125
Asn Leu Val Asp Ile Pro Gln Glu Val Lys Asp Val Ile Gln Phe Ile
130 135 140
Pro Val Asp Thr Tyr Gln Pro Ile Tyr Asp Phe Ile Phe
145 150 155
<210> 9
<211> 1128
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clones pAD641 and pAD1033
<400> 9
aaaaaacttt tagatacttt aggggctgaa tttagtccaa aagcacttgt ttcttcgctt 60
tcgatctcac aaaagcaatt tatcgaaatc gccaaagctt tatcccaaaa accggaaatt 120
atcatttttg atgaaccgac ttcggttcta accgaaaaag atacccaaaa actttatctg 180
cttgttgaaa aacttaaaaa acaaggaatt gcaatcgtct gaattaccca tagaatggaa 240
gaaattaaga aaacttgtga atttatcact gtgattcgaa acggaatgta tattgaaagt 300
aagccaataa atgaatttaa aaacgaagat gagattattt ctttaatggt cggttttgat 360
atcgagcagc gctatcccga aaaaacgccg gttagaagta aaaaaccatc gtttttagtt 420
agaaatttat caaatgataa agtttctaat atcagttttg aaatcaaacc aggtgaaatt 480
ttagtttttt atggccttgt aagttcaggt cgaactgaat tagctagaac tttaattggc 540
gatatgcctt atttaaatgg tcatattgaa ctaaatggtc aagaatttcg cccaaaaaat 600
attaaggaca gtcttgatca tggaatttat tatctttctg aaaataggaa acaaattggt 660
ctaaatgtta atttaccaat taattttaat atcacaattt cttctcttgg ctcaaatcag 720
attttttctt tccttccttt tgtctcaaaa gcaaaaataa ctaaaactac aaatcattat 780
attaaacaat taaagatcaa aacaacttca caagatacgc cattaacttc tttatcaggt 840
ggaaatcaac aaaaagtttc acttgcaaaa gggcttgcaa cccaaccgca agttttcatc 900
ctcgatgaac caactcgcgg agtcgatgtt ggcgcaagaa aggaaattta taatttaatt 960
caccaattaa aacaagaaaa taaaacaatt atgataattt cttcggatat gcaagaggtt 1020
atcggaatcg ctgatcgggt aattacaatg tatgaaggca gaattacaag tgaattagtt 1080
ggcccgcaaa ttaccgatca aaatataatg aaatattcac ttaattta 1128
<210> 10
<211> 376
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clones pAD641 and pAD1033
<400> 10
Lys Lys Leu Leu Asp Thr Leu Gly Ala Glu Phe Ser Pro Lys Ala Leu
1 5 10 15
Val Ser Ser Leu Ser Ile Ser Gln Lys Gln Phe Ile Glu Ile Ala Lys
20 25 30
Ala Leu Ser Gln Lys Pro Glu Ile Ile Ile Phe Asp Glu Pro Thr Ser
35 40 45
Val Leu Thr Glu Lys Asp Thr Gln Lys Leu Tyr Leu Leu Val Glu Lys
50 55 60
Leu Lys Lys Gln Gly Ile Ala Ile Val Trp Ile Thr His Arg Met Glu
65 70 75 80
Glu Ile Lys Lys Thr Cys Glu Phe Ile Thr Val Ile Arg Asn Gly Met
85 90 95
Tyr Ile Glu Ser Lys Pro Ile Asn Glu Phe Lys Asn Glu Asp Glu Ile
100 105 110
Ile Ser Leu Met Val Gly Phe Asp Ile Glu Gln Arg Tyr Pro Glu Lys
115 120 125
Thr Pro Val Arg Ser Lys Lys Pro Ser Phe Leu Val Arg Asn Leu Ser
130 135 140
Asn Asp Lys Val Ser Asn Ile Ser Phe Glu Ile Lys Pro Gly Glu Ile
145 150 155 160
Leu Val Phe Tyr Gly Leu Val Ser Ser Gly Arg Thr Glu Leu Ala Arg
165 170 175
Thr Leu Ile Gly Asp Met Pro Tyr Leu Asn Gly His Ile Glu Leu Asn
180 185 190
Gly Gln Glu Phe Arg Pro Lys Asn Ile Lys Asp Ser Leu Asp His Gly
195 200 205
Ile Tyr Tyr Leu Ser Glu Asn Arg Lys Gln Ile Gly Leu Asn Val Asn
210 215 220
Leu Pro Ile Asn Phe Asn Ile Thr Ile Ser Ser Leu Gly Ser Asn Gln
225 230 235 240
Ile Phe Ser Phe Leu Pro Phe Val Ser Lys Ala Lys Ile Thr Lys Thr
245 250 255
Thr Asn His Tyr Ile Lys Gln Leu Lys Ile Lys Thr Thr Ser Gln Asp
260 265 270
Thr Pro Leu Thr Ser Leu Ser Gly Gly Asn Gln Gln Lys Val Ser Leu
275 280 285
Ala Lys Gly Leu Ala Thr Gln Pro Gln Val Phe Ile Leu Asp Glu Pro
290 295 300
Thr Arg Gly Val Asp Val Gly Ala Arg Lys Glu Ile Tyr Asn Leu Ile
305 310 315 320
His Gln Leu Lys Gln Glu Asn Lys Thr Ile Met Ile Ile Ser Ser Asp
325 330 335
Met Gln Glu Val Ile Gly Ile Ala Asp Arg Val Ile Thr Met Tyr Glu
340 345 350
Gly Arg Ile Thr Ser Glu Leu Val Gly Pro Gln Ile Thr Asp Gln Asn
355 360 365
Ile Met Lys Tyr Ser Leu Asn Leu
370 375
<210> 11
<211> 2394
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD653
<400> 11
acagtcggaa ttaacaaaac cgaaatggat gcaaatacca aaagaatgat gtataatgcc 60
gatattactt attcggttca ttctgaatta ggttttgatt atctccggga taatatggtt 120
ttttcagcag ctgaaaaagt tcaaagggga ctaaattttt gcctaatcga tgaagtagac 180
tcaattttga tcgatgaagc caaaacccct ttgattatca gtggtggcaa aactaacctt 240
ccagcccaat atttatccgc gaaccaattt gttaatactc taattgctga agatttttat 300
attgatgaag aaactaaggg aattaaatta aatgataaag gaatcgataa ggcaaatgct 360
ttttttggcc ttcgtaattt atatgaaatt caaaactcag aaatagttca tcgaattcaa 420
aacgcgctga gagccaataa ggtgatgaaa cgcgatgttg aatatattgt ccaggacggc 480
aaaattgcct tagttgatca atttactggg cgaattatgg ctggaagatc ttattctgaa 540
ggtctccagc aagccctgca agcaaaagag gggcttgaaa ttgaacctga gacaaaaaca 600
ctagcaacaa ttacctatca aaattttttt cgccttttta aaaaattatc agggatgacc 660
gggactgcca aaaccgaaga acaagaattt atcgatgttt ataatatgcg cgtgaatgtg 720
attccgacaa acaaaccgat gattcgtaag gatgaaaaag atgaaatttt tgccactagt 780
cacgaaaaaa atcaagctat aatttccgaa gttgaacgtg ttcataaaat ggggcagcca 840
attttaattg gaacctcaca agttgttgac tctgaaacgc tttcggagat gctaaaccaa 900
aaaggacttt atcatacagt attaaatgca aaacaaaacc aacttgaagc cgaaattatt 960
gcccaggcag gacgaaaaaa tgcgattacc atcgcgacaa atatggctgg aagaagaact 1020
gatataattt tagagcctgg tgtgactgaa cttgggcggc tttatattct tggaaccgat 1080
aaagccgaaa ctagaagaat cgataaccaa ctacgaggtc gctctggacg acaaggtgat 1140
gtgggaattt cgcgattttt tatctcactt caggaccaac tttttcggcg ttttaccaat 1200
tttgatcaaa tttttggcgc ttatggacaa acaaatgggg caattaaagg aaaatatatt 1260
catgcggttt tacttgcagc ccaaaagaaa atcgaaggct ttaacttcga tatgcgcaaa 1320
actgtgctta gttatgatga tgttattcgt caacagcgtg atttaattta tgcccaaaga 1380
gatattttgc ttcagattga aaattttgac cattatatcc agaagatgat tattcgggct 1440
gttgatatca ttttaagcta tgattttata attttaccaa atcaagaaat tcactataaa 1500
aatttaataa attttcttaa tgataattta tcaagaatta ctcattttaa ctttgggcaa 1560
attggaattg aaaattatcc cattgaacaa cttaatgaat ttttaatcaa acaattagaa 1620
actatttatt ttaaacaaat ccaatcagtt ttaaaggaaa atcttggaaa aacctacttt 1680
gaatcagaac gttatattat tttatcaaca cttgatagtc agtgacaaaa tcatattgac 1740
accattgaca aattaagatc ttctgctaat ttagttcagt attcccagaa aaatccttat 1800
caaattttta ccgaggaagc aacaaaaaaa ttcaacattt tagtagcaga atccgcttat 1860
caggcaatag tttctttatt taataattca aatgctgaaa aaatagaata tatcaaagca 1920
attttgtctg atggaaccgc aatttcttat ccggcagata gccctcaaga aataattgat 1980
caaataatcg cctctaacga ggagagaatc gcggctgcaa gaaaagcaaa agaagaaaaa 2040
cagcctgaat ttattgaaaa acaacttgct aaactaaaaa ttgaaaaggt tgaatcagga 2100
gaggaatttg aactttgaaa aatcggagat agcaaactag ttaacctaaa aaaggaaatg 2160
cctcttgatg aaaaacaaaa tattttagta aaaatgcagc aggaacaact tgaaatgatg 2220
agcgaggaag aaaaaaacct aatacaagaa caaaatttag agattgtaga gattgaagaa 2280
atagaggaag aaattcaaaa tgaaaatccc caaaaagttg aatttgtgga ttttaaaaat 2340
gatcctgatg catataataa actgatattc ggtgcggatt atgcagataa ccat 2394
<210> 12
<211> 798
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD653
<400> 12
Thr Val Gly Ile Asn Lys Thr Glu Met Asp Ala Asn Thr Lys Arg Met
1 5 10 15
Met Tyr Asn Ala Asp Ile Thr Tyr Ser Val His Ser Glu Leu Gly Phe
20 25 30
Asp Tyr Leu Arg Asp Asn Met Val Phe Ser Ala Ala Glu Lys Val Gln
35 40 45
Arg Gly Leu Asn Phe Cys Leu Ile Asp Glu Val Asp Ser Ile Leu Ile
50 55 60
Asp Glu Ala Lys Thr Pro Leu Ile Ile Ser Gly Gly Lys Thr Asn Leu
65 70 75 80
Pro Ala Gln Tyr Leu Ser Ala Asn Gln Phe Val Asn Thr Leu Ile Ala
85 90 95
Glu Asp Phe Tyr Ile Asp Glu Glu Thr Lys Gly Ile Lys Leu Asn Asp
100 105 110
Lys Gly Ile Asp Lys Ala Asn Ala Phe Phe Gly Leu Arg Asn Leu Tyr
115 120 125
Glu Ile Gln Asn Ser Glu Ile Val His Arg Ile Gln Asn Ala Leu Arg
130 135 140
Ala Asn Lys Val Met Lys Arg Asp Val Glu Tyr Ile Val Gln Asp Gly
145 150 155 160
Lys Ile Ala Leu Val Asp Gln Phe Thr Gly Arg Ile Met Ala Gly Arg
165 170 175
Ser Tyr Ser Glu Gly Leu Gln Gln Ala Leu Gln Ala Lys Glu Gly Leu
180 185 190
Glu Ile Glu Pro Glu Thr Lys Thr Leu Ala Thr Ile Thr Tyr Gln Asn
195 200 205
Phe Phe Arg Leu Phe Lys Lys Leu Ser Gly Met Thr Gly Thr Ala Lys
210 215 220
Thr Glu Glu Gln Glu Phe Ile Asp Val Tyr Asn Met Arg Val Asn Val
225 230 235 240
Ile Pro Thr Asn Lys Pro Met Ile Arg Lys Asp Glu Lys Asp Glu Ile
245 250 255
Phe Ala Thr Ser His Glu Lys Asn Gln Ala Ile Ile Ser Glu Val Glu
260 265 270
Arg Val His Lys Met Gly Gln Pro Ile Leu Ile Gly Thr Ser Gln Val
275 280 285
Val Asp Ser Glu Thr Leu Ser Glu Met Leu Asn Gln Lys Gly Leu Tyr
290 295 300
His Thr Val Leu Asn Ala Lys Gln Asn Gln Leu Glu Ala Glu Ile Ile
305 310 315 320
Ala Gln Ala Gly Arg Lys Asn Ala Ile Thr Ile Ala Thr Asn Met Ala
325 330 335
Gly Arg Arg Thr Asp Ile Ile Leu Glu Pro Gly Val Thr Glu Leu Gly
340 345 350
Arg Leu Tyr Ile Leu Gly Thr Asp Lys Ala Glu Thr Arg Arg Ile Asp
355 360 365
Asn Gln Leu Arg Gly Arg Ser Gly Arg Gln Gly Asp Val Gly Ile Ser
370 375 380
Arg Phe Phe Ile Ser Leu Gln Asp Gln Leu Phe Arg Arg Phe Thr Asn
385 390 395 400
Phe Asp Gln Ile Phe Gly Ala Tyr Gly Gln Thr Asn Gly Ala Ile Lys
405 410 415
Gly Lys Tyr Ile His Ala Val Leu Leu Ala Ala Gln Lys Lys Ile Glu
420 425 430
Gly Phe Asn Phe Asp Met Arg Lys Thr Val Leu Ser Tyr Asp Asp Val
435 440 445
Ile Arg Gln Gln Arg Asp Leu Ile Tyr Ala Gln Arg Asp Ile Leu Leu
450 455 460
Gln Ile Glu Asn Phe Asp His Tyr Ile Gln Lys Met Ile Ile Arg Ala
465 470 475 480
Val Asp Ile Ile Leu Ser Tyr Asp Phe Ile Ile Leu Pro Asn Gln Glu
485 490 495
Ile His Tyr Lys Asn Leu Ile Asn Phe Leu Asn Asp Asn Leu Ser Arg
500 505 510
Ile Thr His Phe Asn Phe Gly Gln Ile Gly Ile Glu Asn Tyr Pro Ile
515 520 525
Glu Gln Leu Asn Glu Phe Leu Ile Lys Gln Leu Glu Thr Ile Tyr Phe
530 535 540
Lys Gln Ile Gln Ser Val Leu Lys Glu Asn Leu Gly Lys Thr Tyr Phe
545 550 555 560
Glu Ser Glu Arg Tyr Ile Ile Leu Ser Thr Leu Asp Ser Gln Trp Gln
565 570 575
Asn His Ile Asp Thr Ile Asp Lys Leu Arg Ser Ser Ala Asn Leu Val
580 585 590
Gln Tyr Ser Gln Lys Asn Pro Tyr Gln Ile Phe Thr Glu Glu Ala Thr
595 600 605
Lys Lys Phe Asn Ile Leu Val Ala Glu Ser Ala Tyr Gln Ala Ile Val
610 615 620
Ser Leu Phe Asn Asn Ser Asn Ala Glu Lys Ile Glu Tyr Ile Lys Ala
625 630 635 640
Ile Leu Ser Asp Gly Thr Ala Ile Ser Tyr Pro Ala Asp Ser Pro Gln
645 650 655
Glu Ile Ile Asp Gln Ile Ile Ala Ser Asn Glu Glu Arg Ile Ala Ala
660 665 670
Ala Arg Lys Ala Lys Glu Glu Lys Gln Pro Glu Phe Ile Glu Lys Gln
675 680 685
Leu Ala Lys Leu Lys Ile Glu Lys Val Glu Ser Gly Glu Glu Phe Glu
690 695 700
Leu Trp Lys Ile Gly Asp Ser Lys Leu Val Asn Leu Lys Lys Glu Met
705 710 715 720
Pro Leu Asp Glu Lys Gln Asn Ile Leu Val Lys Met Gln Gln Glu Gln
725 730 735
Leu Glu Met Met Ser Glu Glu Glu Lys Asn Leu Ile Gln Glu Gln Asn
740 745 750
Leu Glu Ile Val Glu Ile Glu Glu Ile Glu Glu Glu Ile Gln Asn Glu
755 760 765
Asn Pro Gln Lys Val Glu Phe Val Asp Phe Lys Asn Asp Pro Asp Ala
770 775 780
Tyr Asn Lys Leu Ile Phe Gly Ala Asp Tyr Ala Asp Asn His
785 790 795
<210> 13
<211> 1410
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clones pAD657 and pAD964
<400> 13
atgatttcgt atttttattc aaaatcagca ccgcagtgtc ttaaaactga aaatcccaga 60
ttttgttata aactaaataa aaatttagta aaatttcaaa aagaattaga tctattaaaa 120
cagaaaaaac ttgcaccaaa agaatatgaa agccagttta gtgatctaaa agaaaaattt 180
ttagcttatg aagttaatat aaaaaaacat tatcaggcaa aaaaatccta taaattacgt 240
gctatttgag atcggattca aaaatattga catacaagct ttaacagatc ccattttgat 300
tttgaagcat tttctaaaaa tgttgaatat aaacaaatag gaaataaacg tcataaaatt 360
gttgcccgga tcaaaaattt aaacctttcc tttgtcaatc cagcaaatcc cgagattaga 420
aatatcgtga ttcgtaatgc ctcaattgat ttttatgaag gcgaaattca tgccttaatt 480
ggcgagtctg gttcaggaaa atcagtaatt acttcttgtc tttatggtct tgtcggtcaa 540
aacggggtaa ttgaatcagg tgaaatcaaa ctttttaaca atccagtgca aaattttgat 600
tttcgtgctt gagaactttc aaattatcgg ggaaaagtta tttcagctgt cttccagaat 660
ccgatgtcaa ctttaaatcc aacaaaaaaa ataggcatcc aaattatgga aggaatgtta 720
ttaaacaaga ttgttaaaac gaaaaaagaa gcctatgaaa aagcactttt atatcttaga 780
atgaccaaaa ttgctaaccc ggaaatggtt atgaaattat atccccatga gctttcagga 840
ggtatgattc aaagaattgt gatctcagca attttatcac ttgaacctaa aattatcgtt 900
atggatgaac caacaacagc tttggataca accgtgcaag ctttagttct tgatattatc 960
cgcgatctcc aaaaaagact aaaaattaca attattttca ttactcacga ccttggagtt 1020
gtcgcttctc ttgcaactta tatctcaatc atgtatgctg gtcaagttgt cgaggaaggt 1080
acaagagatg aaattctttt aaatccaaga catccatata cttgagggct aattacttca 1140
atgcctgatg tcaataaagg cgaacgactt cagtcaattc gcggggttgt tccttcttct 1200
ttaaattcaa ttgttggcga tgcttttgca gttagaaacg attatgcctt agaacaagat 1260
ttttttattg aacctaaatt ttacagaata agtccaactc accgagtcaa atcagcttta 1320
cttgatccaa aagcaccaaa agttgtccca ccaaaaatta tttaccaaaa atgactgcaa 1380
tttgcaaaga tgaggcaaga aaatggaaga 1410
<210> 14
<211> 470
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clones pAD657 and pAD964
<400> 14
Met Ile Ser Tyr Phe Tyr Ser Lys Ser Ala Pro Gln Cys Leu Lys Thr
1 5 10 15
Glu Asn Pro Arg Phe Cys Tyr Lys Leu Asn Lys Asn Leu Val Lys Phe
20 25 30
Gln Lys Glu Leu Asp Leu Leu Lys Gln Lys Lys Leu Ala Pro Lys Glu
35 40 45
Tyr Glu Ser Gln Phe Ser Asp Leu Lys Glu Lys Phe Leu Ala Tyr Glu
50 55 60
Val Asn Ile Lys Lys His Tyr Gln Ala Lys Lys Ser Tyr Lys Leu Arg
65 70 75 80
Ala Ile Trp Asp Arg Ile Gln Lys Tyr Trp His Thr Ser Phe Asn Arg
85 90 95
Ser His Phe Asp Phe Glu Ala Phe Ser Lys Asn Val Glu Tyr Lys Gln
100 105 110
Ile Gly Asn Lys Arg His Lys Ile Val Ala Arg Ile Lys Asn Leu Asn
115 120 125
Leu Ser Phe Val Asn Pro Ala Asn Pro Glu Ile Arg Asn Ile Val Ile
130 135 140
Arg Asn Ala Ser Ile Asp Phe Tyr Glu Gly Glu Ile His Ala Leu Ile
145 150 155 160
Gly Glu Ser Gly Ser Gly Lys Ser Val Ile Thr Ser Cys Leu Tyr Gly
165 170 175
Leu Val Gly Gln Asn Gly Val Ile Glu Ser Gly Glu Ile Lys Leu Phe
180 185 190
Asn Asn Pro Val Gln Asn Phe Asp Phe Arg Ala Trp Glu Leu Ser Asn
195 200 205
Tyr Arg Gly Lys Val Ile Ser Ala Val Phe Gln Asn Pro Met Ser Thr
210 215 220
Leu Asn Pro Thr Lys Lys Ile Gly Ile Gln Ile Met Glu Gly Met Leu
225 230 235 240
Leu Asn Lys Ile Val Lys Thr Lys Lys Glu Ala Tyr Glu Lys Ala Leu
245 250 255
Leu Tyr Leu Arg Met Thr Lys Ile Ala Asn Pro Glu Met Val Met Lys
260 265 270
Leu Tyr Pro His Glu Leu Ser Gly Gly Met Ile Gln Arg Ile Val Ile
275 280 285
Ser Ala Ile Leu Ser Leu Glu Pro Lys Ile Ile Val Met Asp Glu Pro
290 295 300
Thr Thr Ala Leu Asp Thr Thr Val Gln Ala Leu Val Leu Asp Ile Ile
305 310 315 320
Arg Asp Leu Gln Lys Arg Leu Lys Ile Thr Ile Ile Phe Ile Thr His
325 330 335
Asp Leu Gly Val Val Ala Ser Leu Ala Thr Tyr Ile Ser Ile Met Tyr
340 345 350
Ala Gly Gln Val Val Glu Glu Gly Thr Arg Asp Glu Ile Leu Leu Asn
355 360 365
Pro Arg His Pro Tyr Thr Trp Gly Leu Ile Thr Ser Met Pro Asp Val
370 375 380
Asn Lys Gly Glu Arg Leu Gln Ser Ile Arg Gly Val Val Pro Ser Ser
385 390 395 400
Leu Asn Ser Ile Val Gly Asp Ala Phe Ala Val Arg Asn Asp Tyr Ala
405 410 415
Leu Glu Gln Asp Phe Phe Ile Glu Pro Lys Phe Tyr Arg Ile Ser Pro
420 425 430
Thr His Arg Val Lys Ser Ala Leu Leu Asp Pro Lys Ala Pro Lys Val
435 440 445
Val Pro Pro Lys Ile Ile Tyr Gln Lys Trp Leu Gln Phe Ala Lys Met
450 455 460
Arg Gln Glu Asn Gly Arg
465 470
<210> 15
<211> 1332
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clones pAD659 and pAD910
<400> 15
atgaaaaata ttgaaaaaag tgaaataatt atctcccttg ttgatgttga taaagaattt 60
ggtgataaaa aagttttaga tcaaataaat ttggacatta aacgaggaga ttttgtcaca 120
cttttagggc cctcagggtc cgggaagaca acaattttac gtttaattgg tggttttgaa 180
tgaactactc gcggcgaaat caaatttaat ggcatcgata taaaagacgt tccggcacat 240
aaacgtgata cagctacaat ttttcaagat tatgcacttt ttccacattt atcagttcgt 300
ggaaatattg aatttggtct taaattaaaa agaattaaaa aaaaggcaga agaaattccg 360
gatgtagtct ggaaaaaatt tgagcactta aagaaaaaat gacaggataa gcaaaagcga 420
aagattaaag agttaaaaat tttacaggct catttagaaa aactgcttga aaatccacag 480
ttagatatta aaaaacgtaa aaaattacag gataaattag atgattctga ttttagatat 540
tcaaattgag aaaattatct aacatccaaa tcagaaagtt ttaaaaaaaa atacctaacc 600
cgaaagatca caaaacagga aattaataaa gaaattaccg atattattga ccttgttggt 660
ctaactggaa atgaaaatcg agcaatttcg gaattatcag gaggaatgaa acaacgcgta 720
gcacttgcaa gatcgcttgt aattgagcct gaaattgtcc tacttgatga acctttatca 780
gctttagata caaaaattag gcaaaaaatg caagtttttc taaaaaaaat tcaacaaaaa 840
cttggcctaa cttttatttt tgttactcat gatcaagatg aagccttgca attatcagat 900
aaaatcgcca taatccgtaa tggaaaaatc gcccaatacg atgaaccaaa acaaatttat 960
gactatccag ttaataaatg ggtggctaat tttattggtg attctaattt ttttcaggca 1020
aaatacatta aaaaaaatca ggtcgaaatt cttggtctta aattatatac aattcatgat 1080
gagtttatcc caggccaaaa attagattgc ctgattcgtc cagaagatat cgatattgac 1140
ctaaattcag gctattttaa aggaaaagtt atccaaaata tttataaagg ttcatactat 1200
tcacttgata tcaaagtaga aaatacaata attaatgtcg aaactaacga tttttatgac 1260
ctcgagactc aagtttttct aaaatgagat gatgatgcta ttcatttaat ggagatggaa 1320
aatgctgaaa tt 1332
<210> 16
<211> 444
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clones pAD659 and pAD910
<400> 16
Met Lys Asn Ile Glu Lys Ser Glu Ile Ile Ile Ser Leu Val Asp Val
1 5 10 15
Asp Lys Glu Phe Gly Asp Lys Lys Val Leu Asp Gln Ile Asn Leu Asp
20 25 30
Ile Lys Arg Gly Asp Phe Val Thr Leu Leu Gly Pro Ser Gly Ser Gly
35 40 45
Lys Thr Thr Ile Leu Arg Leu Ile Gly Gly Phe Glu Trp Thr Thr Arg
50 55 60
Gly Glu Ile Lys Phe Asn Gly Ile Asp Ile Lys Asp Val Pro Ala His
65 70 75 80
Lys Arg Asp Thr Ala Thr Ile Phe Gln Asp Tyr Ala Leu Phe Pro His
85 90 95
Leu Ser Val Arg Gly Asn Ile Glu Phe Gly Leu Lys Leu Lys Arg Ile
100 105 110
Lys Lys Lys Ala Glu Glu Ile Pro Asp Val Val Trp Lys Lys Phe Glu
115 120 125
His Leu Lys Lys Lys Trp Gln Asp Lys Gln Lys Arg Lys Ile Lys Glu
130 135 140
Leu Lys Ile Leu Gln Ala His Leu Glu Lys Leu Leu Glu Asn Pro Gln
145 150 155 160
Leu Asp Ile Lys Lys Arg Lys Lys Leu Gln Asp Lys Leu Asp Asp Ser
165 170 175
Asp Phe Arg Tyr Ser Asn Trp Glu Asn Tyr Leu Thr Ser Lys Ser Glu
180 185 190
Ser Phe Lys Lys Lys Tyr Leu Thr Arg Lys Ile Thr Lys Gln Glu Ile
195 200 205
Asn Lys Glu Ile Thr Asp Ile Ile Asp Leu Val Gly Leu Thr Gly Asn
210 215 220
Glu Asn Arg Ala Ile Ser Glu Leu Ser Gly Gly Met Lys Gln Arg Val
225 230 235 240
Ala Leu Ala Arg Ser Leu Val Ile Glu Pro Glu Ile Val Leu Leu Asp
245 250 255
Glu Pro Leu Ser Ala Leu Asp Thr Lys Ile Arg Gln Lys Met Gln Val
260 265 270
Phe Leu Lys Lys Ile Gln Gln Lys Leu Gly Leu Thr Phe Ile Phe Val
275 280 285
Thr His Asp Gln Asp Glu Ala Leu Gln Leu Ser Asp Lys Ile Ala Ile
290 295 300
Ile Arg Asn Gly Lys Ile Ala Gln Tyr Asp Glu Pro Lys Gln Ile Tyr
305 310 315 320
Asp Tyr Pro Val Asn Lys Trp Val Ala Asn Phe Ile Gly Asp Ser Asn
325 330 335
Phe Phe Gln Ala Lys Tyr Ile Lys Lys Asn Gln Val Glu Ile Leu Gly
340 345 350
Leu Lys Leu Tyr Thr Ile His Asp Glu Phe Ile Pro Gly Gln Lys Leu
355 360 365
Asp Cys Leu Ile Arg Pro Glu Asp Ile Asp Ile Asp Leu Asn Ser Gly
370 375 380
Tyr Phe Lys Gly Lys Val Ile Gln Asn Ile Tyr Lys Gly Ser Tyr Tyr
385 390 395 400
Ser Leu Asp Ile Lys Val Glu Asn Thr Ile Ile Asn Val Glu Thr Asn
405 410 415
Asp Phe Tyr Asp Leu Glu Thr Gln Val Phe Leu Lys Trp Asp Asp Asp
420 425 430
Ala Ile His Leu Met Glu Met Glu Asn Ala Glu Ile
435 440
<210> 17
<211> 1590
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD662
<400> 17
gatattaaat tgaaaaaaac taatattcta tcactaaaaa aaataaaaaa agtttatggt 60
cctgtaattg ctctttctga tgtgactttt gttgttccaa aaggggaaat aactagccta 120
gttggtgaaa atggcgcggg aaaatcgaca cttttaaaaa ttttatcagg agtgattcct 180
gctggacaat atgaaggtga tctaattttt gaagataaaa ttatggcttt tgcaaataca 240
aaagcctccg aacgtgtcgg aattgcaata attcatcaag aactttcaat ttcaccttat 300
ttatcaattt gcgagaacat gtatatcggt aattatccga ctaaatttgg caaagttaac 360
tgaaataaga tgatttccga atgcaaaaaa tatctagaaa tggtcggtct tgatgaagat 420
ccaacaacaa ttgctggctc tctttcgatt gcaaaacagc aaatggttga gatcgcaaaa 480
gcactttcaa aaaatgcaaa actactaatt ttagatgaac cgacttcctc tttaaatgat 540
gaaaatgctt ttcgcttact tgatattatg aaaagtttaa aaagtaaagg aattacttcg 600
atttttgtct cccataaatt aaatgaagtc aaatatgtct ctgataatat tgttgtaatc 660
cgcgatggta aattcatttc ccagtataat aaaaatgaag aaataattga tgaaaaccgg 720
ctaattcagg acattgttgg ccggccttta aagtccaaat ttcctcctag ggatttagat 780
cgaaaaatcg gggaaattat ttttgagatc aaagatatag ttattcctca tgctagtatt 840
gcaaattata atgttgtcaa aaatgcttcc cttgatgtta aacaaggcga aattgtcgga 900
atttccggac ttgttggatc gggtcgaacc gaattaatgc tttcactttt tgggcagtat 960
tataacaaac cttcaagtgg caaagttttc tataaaggta aagaagtaaa atttactaac 1020
acaaaacagg caatcaaatc gggaattatg tatgcttccg aagatcgaaa aaatgttggt 1080
ctaatccaaa ttttttcgat tcaaaataat atcacttccg ccgctttgca tttattttca 1140
aaatgaggaa ttctaaataa aaataaggaa ataattaatg cccaaaaact aaaaaaagat 1200
gtaagtatta aaacaaaaaa tattctaaat aatgtcgaat ccctttctgg gggaaatcag 1260
caaaaagttg taattgccaa agctttaagc accaaatttg accttctaat tatcgatgag 1320
ccaacaaaag gtattgatgt tggctcaaaa tacgaaattt ataaaatttt actagacctt 1380
tcatcacaag gtaaaacaat tattgtaatc tcttcggaaa ttgaagaact tttaggaatc 1440
accgatcacc tttattttgt gactggaaaa ctttttggtc aaaatcaaga ctgactttcc 1500
cagtttttgc atctttttta taactttttt gaccaaaagg attaccataa ggacttccaa 1560
attttgagac ataatcttgg tgaagcgagt 1590
<210> 18
<211> 530
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD662
<400> 18
Asp Ile Lys Leu Lys Lys Thr Asn Ile Leu Ser Leu Lys Lys Ile Lys
1 5 10 15
Lys Val Tyr Gly Pro Val Ile Ala Leu Ser Asp Val Thr Phe Val Val
20 25 30
Pro Lys Gly Glu Ile Thr Ser Leu Val Gly Glu Asn Gly Ala Gly Lys
35 40 45
Ser Thr Leu Leu Lys Ile Leu Ser Gly Val Ile Pro Ala Gly Gln Tyr
50 55 60
Glu Gly Asp Leu Ile Phe Glu Asp Lys Ile Met Ala Phe Ala Asn Thr
65 70 75 80
Lys Ala Ser Glu Arg Val Gly Ile Ala Ile Ile His Gln Glu Leu Ser
85 90 95
Ile Ser Pro Tyr Leu Ser Ile Cys Glu Asn Met Tyr Ile Gly Asn Tyr
100 105 110
Pro Thr Lys Phe Gly Lys Val Asn Trp Asn Lys Met Ile Ser Glu Cys
115 120 125
Lys Lys Tyr Leu Glu Met Val Gly Leu Asp Glu Asp Pro Thr Thr Ile
130 135 140
Ala Gly Ser Leu Ser Ile Ala Lys Gln Gln Met Val Glu Ile Ala Lys
145 150 155 160
Ala Leu Ser Lys Asn Ala Lys Leu Leu Ile Leu Asp Glu Pro Thr Ser
165 170 175
Ser Leu Asn Asp Glu Asn Ala Phe Arg Leu Leu Asp Ile Met Lys Ser
180 185 190
Leu Lys Ser Lys Gly Ile Thr Ser Ile Phe Val Ser His Lys Leu Asn
195 200 205
Glu Val Lys Tyr Val Ser Asp Asn Ile Val Val Ile Arg Asp Gly Lys
210 215 220
Phe Ile Ser Gln Tyr Asn Lys Asn Glu Glu Ile Ile Asp Glu Asn Arg
225 230 235 240
Leu Ile Gln Asp Ile Val Gly Arg Pro Leu Lys Ser Lys Phe Pro Pro
245 250 255
Arg Asp Leu Asp Arg Lys Ile Gly Glu Ile Ile Phe Glu Ile Lys Asp
260 265 270
Ile Val Ile Pro His Ala Ser Ile Ala Asn Tyr Asn Val Val Lys Asn
275 280 285
Ala Ser Leu Asp Val Lys Gln Gly Glu Ile Val Gly Ile Ser Gly Leu
290 295 300
Val Gly Ser Gly Arg Thr Glu Leu Met Leu Ser Leu Phe Gly Gln Tyr
305 310 315 320
Tyr Asn Lys Pro Ser Ser Gly Lys Val Phe Tyr Lys Gly Lys Glu Val
325 330 335
Lys Phe Thr Asn Thr Lys Gln Ala Ile Lys Ser Gly Ile Met Tyr Ala
340 345 350
Ser Glu Asp Arg Lys Asn Val Gly Leu Ile Gln Ile Phe Ser Ile Gln
355 360 365
Asn Asn Ile Thr Ser Ala Ala Leu His Leu Phe Ser Lys Trp Gly Ile
370 375 380
Leu Asn Lys Asn Lys Glu Ile Ile Asn Ala Gln Lys Leu Lys Lys Asp
385 390 395 400
Val Ser Ile Lys Thr Lys Asn Ile Leu Asn Asn Val Glu Ser Leu Ser
405 410 415
Gly Gly Asn Gln Gln Lys Val Val Ile Ala Lys Ala Leu Ser Thr Lys
420 425 430
Phe Asp Leu Leu Ile Ile Asp Glu Pro Thr Lys Gly Ile Asp Val Gly
435 440 445
Ser Lys Tyr Glu Ile Tyr Lys Ile Leu Leu Asp Leu Ser Ser Gln Gly
450 455 460
Lys Thr Ile Ile Val Ile Ser Ser Glu Ile Glu Glu Leu Leu Gly Ile
465 470 475 480
Thr Asp His Leu Tyr Phe Val Thr Gly Lys Leu Phe Gly Gln Asn Gln
485 490 495
Asp Trp Leu Ser Gln Phe Leu His Leu Phe Tyr Asn Phe Phe Asp Gln
500 505 510
Lys Asp Tyr His Lys Asp Phe Gln Ile Leu Arg His Asn Leu Gly Glu
515 520 525
Ala Ser
530
<210> 19
<211> 852
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD681
<400> 19
atcgaaacca tcaaaattga gctgggtgag cagctcgaat tttttgaaaa aaataataaa 60
ttagtcgaaa aacaacgact aaaagaccga gtcaataatg atattgactc gctttctgaa 120
ttcggaattt gttcaggaat tgagaattat gcccgccata ttgacggacg ccaaaaaggc 180
gaaaaaccat ttagtttact agattattta ccccaagacg gcctaatttt tattgatgaa 240
tcccatatta tgatcagcca aattaagggc atgtatgaag gtgatcgaag ccgaaaacaa 300
accttggttg actatggtta tcgactacct tcagctcttg ataatcggcc cttaaaactc 360
agtgaatttg agaaatatca acaggcaaaa atttatgttt cagccacacc ggccagctat 420
gaaattgata aaacaaatgg cgaaattgtc tcgcaaatta tcagaccaac tggactaatt 480
gatccagaaa tagtaattga atctaccaaa aatcaaatgg agaaaatttt tcagtatttg 540
ctaaaacaga aggaaaaaaa agaaagaagt ctcattttaa ctaccacaaa acgactggcc 600
gaagaaatca gcaagtatct ccaggaagaa aaattacaaa atgtctatta tttgcactca 660
gaaatgacga cttttgagcg cgatgaaatc ataattaagc ttcgaaaagg aatttatgat 720
gcaattgtcg ggataaattt acttcgtgaa ggcgttgata tcccggaagt ttctttgatt 780
tttgttcttg aagccggtct tgtttctttt ttgcgatccg catgcgagct cggtaccccg 840
ggtcgacctg ca 852
<210> 20
<211> 284
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD681
<400> 20
Ile Glu Thr Ile Lys Ile Glu Leu Gly Glu Gln Leu Glu Phe Phe Glu
1 5 10 15
Lys Asn Asn Lys Leu Val Glu Lys Gln Arg Leu Lys Asp Arg Val Asn
20 25 30
Asn Asp Ile Asp Ser Leu Ser Glu Phe Gly Ile Cys Ser Gly Ile Glu
35 40 45
Asn Tyr Ala Arg His Ile Asp Gly Arg Gln Lys Gly Glu Lys Pro Phe
50 55 60
Ser Leu Leu Asp Tyr Leu Pro Gln Asp Gly Leu Ile Phe Ile Asp Glu
65 70 75 80
Ser His Ile Met Ile Ser Gln Ile Lys Gly Met Tyr Glu Gly Asp Arg
85 90 95
Ser Arg Lys Gln Thr Leu Val Asp Tyr Gly Tyr Arg Leu Pro Ser Ala
100 105 110
Leu Asp Asn Arg Pro Leu Lys Leu Ser Glu Phe Glu Lys Tyr Gln Gln
115 120 125
Ala Lys Ile Tyr Val Ser Ala Thr Pro Ala Ser Tyr Glu Ile Asp Lys
130 135 140
Thr Asn Gly Glu Ile Val Ser Gln Ile Ile Arg Pro Thr Gly Leu Ile
145 150 155 160
Asp Pro Glu Ile Val Ile Glu Ser Thr Lys Asn Gln Met Glu Lys Ile
165 170 175
Phe Gln Tyr Leu Leu Lys Gln Lys Glu Lys Lys Glu Arg Ser Leu Ile
180 185 190
Leu Thr Thr Thr Lys Arg Leu Ala Glu Glu Ile Ser Lys Tyr Leu Gln
195 200 205
Glu Glu Lys Leu Gln Asn Val Tyr Tyr Leu His Ser Glu Met Thr Thr
210 215 220
Phe Glu Arg Asp Glu Ile Ile Ile Lys Leu Arg Lys Gly Ile Tyr Asp
225 230 235 240
Ala Ile Val Gly Ile Asn Leu Leu Arg Glu Gly Val Asp Ile Pro Glu
245 250 255
Val Ser Leu Ile Phe Val Leu Glu Ala Gly Leu Val Ser Phe Leu Arg
260 265 270
Ser Ala Cys Glu Leu Gly Thr Pro Gly Arg Pro Ala
275 280
<210> 21
<211> 843
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD700
<400> 21
atgcccaaat taaaccgact tagagcccga tttgtccaga ttcaaaacat tgaaaaaatg 60
acaaatgtaa tggaaatgat tgcgaatgca aaaattccaa aaataaaaaa caagtttaaa 120
attgttcaag aatattttga aaatttagat tatatttttc aaaatattct tgcaaattta 180
tctaagaagg ttgaggaatt aactaatgct gattccaaaa aaaatcttta tattattttt 240
ggatcaaatt taggtttttg tggtgccctt aataatttaa tcttaaaaaa tgttgtccca 300
caacttcaga aaaatgatga aattatcgtc tttggtgaaa aaatttataa ttttttgtca 360
ataaattact ctaatttaat tattaaattt tttctaaata ttgaagaaac taattttagt 420
gaaccaattt tagaaatctc aaactttgta aatcaatcga tttttgagag aaaatataaa 480
aaaattttta tttgttataa caaatttatc agtattatac attcaagccc agagatgcaa 540
aatttatttg atttcaaaaa aaatactata aaatacggtg gttacgggat tgagtttgaa 600
ccaaatgcta ctgaggtttt taaaaaatta atgccctttt atataaaatc catccttgaa 660
aaacttttta tcgaatccaa attagttgag acttcaacta gacgaacatc aatggaaagt 720
gcactgaaaa tgccagttga aattttgcat aagtttagaa acagaaataa ttccagtcgt 780
ccagccatga ttaccccaga aattattgag attattagtg gtaaaatgtt gaaaaagtta 840
ggt 843
<210> 22
<211> 281
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD700
<400> 22
Met Pro Lys Leu Asn Arg Leu Arg Ala Arg Phe Val Gln Ile Gln Asn
1 5 10 15
Ile Glu Lys Met Thr Asn Val Met Glu Met Ile Ala Asn Ala Lys Ile
20 25 30
Pro Lys Ile Lys Asn Lys Phe Lys Ile Val Gln Glu Tyr Phe Glu Asn
35 40 45
Leu Asp Tyr Ile Phe Gln Asn Ile Leu Ala Asn Leu Ser Lys Lys Val
50 55 60
Glu Glu Leu Thr Asn Ala Asp Ser Lys Lys Asn Leu Tyr Ile Ile Phe
65 70 75 80
Gly Ser Asn Leu Gly Phe Cys Gly Ala Leu Asn Asn Leu Ile Leu Lys
85 90 95
Asn Val Val Pro Gln Leu Gln Lys Asn Asp Glu Ile Ile Val Phe Gly
100 105 110
Glu Lys Ile Tyr Asn Phe Leu Ser Ile Asn Tyr Ser Asn Leu Ile Ile
115 120 125
Lys Phe Phe Leu Asn Ile Glu Glu Thr Asn Phe Ser Glu Pro Ile Leu
130 135 140
Glu Ile Ser Asn Phe Val Asn Gln Ser Ile Phe Glu Arg Lys Tyr Lys
145 150 155 160
Lys Ile Phe Ile Cys Tyr Asn Lys Phe Ile Ser Ile Ile His Ser Ser
165 170 175
Pro Glu Met Gln Asn Leu Phe Asp Phe Lys Lys Asn Thr Ile Lys Tyr
180 185 190
Gly Gly Tyr Gly Ile Glu Phe Glu Pro Asn Ala Thr Glu Val Phe Lys
195 200 205
Lys Leu Met Pro Phe Tyr Ile Lys Ser Ile Leu Glu Lys Leu Phe Ile
210 215 220
Glu Ser Lys Leu Val Glu Thr Ser Thr Arg Arg Thr Ser Met Glu Ser
225 230 235 240
Ala Leu Lys Met Pro Val Glu Ile Leu His Lys Phe Arg Asn Arg Asn
245 250 255
Asn Ser Ser Arg Pro Ala Met Ile Thr Pro Glu Ile Ile Glu Ile Ile
260 265 270
Ser Gly Lys Met Leu Lys Lys Leu Gly
275 280
<210> 23
<211> 615
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD711
<400> 23
tcaggtatgt caaaaaatat taaggaaatt tcaatcctac cccttaaatt aaatcctgct 60
ggaattatgc ctgtaatttt tgccttaatt atcgtttcac tgccgacact ttttagcgga 120
tttcttgata gaaatacctc agcagttcgg aattgaatag ataataatat gcaaatttat 180
cacccaatcg gtcttatcat ttttattgtt tttaatgtct ccttttcaat aataatgtcc 240
ttacaacaat cccgagttga taaaattgca caggattttg ccaaaaattc aacttttatc 300
cctgggattc gcccaggaga acagactgaa gattatttaa tttcagtggt tttgcgactt 360
tcagttttca gtgcgattta tcttaccttt ttaggaattc tccaacctgt tgaaattatg 420
ttaggtcttc cttcggcaat cacaatttca ggaacttcga taataatttt agcaacaact 480
acacttgaaa cgatttcgca gatcaaagcc cgttatgatg cacaaaaagt tctaaaacaa 540
agtaaaaaga tccgcaaaaa tttacaagtt cgaaaaaatt ctccttctat tgattcaaat 600
caggatcttt tatgg 615
<210> 24
<211> 205
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD711
<400> 24
Ser Gly Met Ser Lys Asn Ile Lys Glu Ile Ser Ile Leu Pro Leu Lys
1 5 10 15
Leu Asn Pro Ala Gly Ile Met Pro Val Ile Phe Ala Leu Ile Ile Val
20 25 30
Ser Leu Pro Thr Leu Phe Ser Gly Phe Leu Asp Arg Asn Thr Ser Ala
35 40 45
Val Arg Asn Trp Ile Asp Asn Asn Met Gln Ile Tyr His Pro Ile Gly
50 55 60
Leu Ile Ile Phe Ile Val Phe Asn Val Ser Phe Ser Ile Ile Met Ser
65 70 75 80
Leu Gln Gln Ser Arg Val Asp Lys Ile Ala Gln Asp Phe Ala Lys Asn
85 90 95
Ser Thr Phe Ile Pro Gly Ile Arg Pro Gly Glu Gln Thr Glu Asp Tyr
100 105 110
Leu Ile Ser Val Val Leu Arg Leu Ser Val Phe Ser Ala Ile Tyr Leu
115 120 125
Thr Phe Leu Gly Ile Leu Gln Pro Val Glu Ile Met Leu Gly Leu Pro
130 135 140
Ser Ala Ile Thr Ile Ser Gly Thr Ser Ile Ile Ile Leu Ala Thr Thr
145 150 155 160
Thr Leu Glu Thr Ile Ser Gln Ile Lys Ala Arg Tyr Asp Ala Gln Lys
165 170 175
Val Leu Lys Gln Ser Lys Lys Ile Arg Lys Asn Leu Gln Val Arg Lys
180 185 190
Asn Ser Pro Ser Ile Asp Ser Asn Gln Asp Leu Leu Trp
195 200 205
<210> 25
<211> 648
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD721
<400> 25
atcgccgaag aagtttcaag tttttctccg tttgaccgac ttttattttt taggatgtta 60
gatactgcaa ctgcaggtga tattttcacc tacttttcac cagaaattca gaccaaatta 120
gtactaagtt taccaaatga gctaatcaat aaattacttg atgaacttta tgttgatgaa 180
attgtcgaac ttcttgatga agtccctgat aatgttgcca aaagaatttt gcgcaacatt 240
gacattgata ctcgtaaaca aataaatcaa cttttgcagt ataccgacga tcaaattggc 300
gcttttatgt cagttgatat cgtctatctt tttaaagatt cgacttgtca tcaagcactt 360
gaaaaaatta gaaactataa agatatctcc gaattagtgc attattatta tgtcgttgat 420
caaaacaaga aaataatcgg ggcaactact ttagaagata ttgtcttttc tgatcctaat 480
actcagatca aagaaattgt ttttcaagtc ccttttcttg ttacactgat aaaaaagatt 540
atgccgccga agtttttgcc caaaatgatt tttccagtac tcccggttgt taataccagc 600
cagaaactaa tccgaatggt tccagttgat gatattatcc gatattgt 648
<210> 26
<211> 216
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD721
<400> 26
Ile Ala Glu Glu Val Ser Ser Phe Ser Pro Phe Asp Arg Leu Leu Phe
1 5 10 15
Phe Arg Met Leu Asp Thr Ala Thr Ala Gly Asp Ile Phe Thr Tyr Phe
20 25 30
Ser Pro Glu Ile Gln Thr Lys Leu Val Leu Ser Leu Pro Asn Glu Leu
35 40 45
Ile Asn Lys Leu Leu Asp Glu Leu Tyr Val Asp Glu Ile Val Glu Leu
50 55 60
Leu Asp Glu Val Pro Asp Asn Val Ala Lys Arg Ile Leu Arg Asn Ile
65 70 75 80
Asp Ile Asp Thr Arg Lys Gln Ile Asn Gln Leu Leu Gln Tyr Thr Asp
85 90 95
Asp Gln Ile Gly Ala Phe Met Ser Val Asp Ile Val Tyr Leu Phe Lys
100 105 110
Asp Ser Thr Cys His Gln Ala Leu Glu Lys Ile Arg Asn Tyr Lys Asp
115 120 125
Ile Ser Glu Leu Val His Tyr Tyr Tyr Val Val Asp Gln Asn Lys Lys
130 135 140
Ile Ile Gly Ala Thr Thr Leu Glu Asp Ile Val Phe Ser Asp Pro Asn
145 150 155 160
Thr Gln Ile Lys Glu Ile Val Phe Gln Val Pro Phe Leu Val Thr Leu
165 170 175
Ile Lys Lys Ile Met Pro Pro Lys Phe Leu Pro Lys Met Ile Phe Pro
180 185 190
Val Leu Pro Val Val Asn Thr Ser Gln Lys Leu Ile Arg Met Val Pro
195 200 205
Val Asp Asp Ile Ile Arg Tyr Cys
210 215
<210> 27
<211> 837
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD727
<400> 27
tcatttggtt caggatttaa tttagcaatt gattttagtg gcggaactaa ctttttaatt 60
gaaagctcaa attcaagtta tgatttaatt acaaaggaaa aagccgaaaa aataattagt 120
tttcttgatt cacaaaatat aaacaagtca aattcaacaa ttttgcttaa tccattaaat 180
gaaaatggaa atatttttaa tcttgaaatt aaaacaaaac ttgatctagc aacaaaaatt 240
gcctcattaa atacggcaat ccagaataat ttttctaata ttcgaatgac aaattattca 300
atttcgaatg aagaagctca aaaattaatt ttcaatgcaa ttctttcagt tggaatcgca 360
cttatttttg taactatttt tacgctaatt aggtttaaat ggactttttc gcttgcaata 420
attttctcac ttctttttaa tgttttaatg gttttgctag caattattat tacacggatc 480
gaaatatcgc agaatttagt tgttgcaatt cttactttaa ttggttatac agtaaatgat 540
acaatcgtgg tttttgatag agtaaaagca agattttcag aaataaatca tgaaaatgtt 600
tataaatttg ataaaattaa agaaatttcc ttacaagcaa ttagagaaac agcaaaaagg 660
tcggtatata catccttgac aaccatttta acaattgttg ttttaatgat tttttatgaa 720
tcaattgata ttgtctttag cctgacgatg ttaattggtg tgataattgg aacatattcc 780
tccttattta tcgcaacccg catttggatt attcttgaat catcccgtaa tcgtaaa 837
<210> 28
<211> 279
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD727
<400> 28
Ser Phe Gly Ser Gly Phe Asn Leu Ala Ile Asp Phe Ser Gly Gly Thr
1 5 10 15
Asn Phe Leu Ile Glu Ser Ser Asn Ser Ser Tyr Asp Leu Ile Thr Lys
20 25 30
Glu Lys Ala Glu Lys Ile Ile Ser Phe Leu Asp Ser Gln Asn Ile Asn
35 40 45
Lys Ser Asn Ser Thr Ile Leu Leu Asn Pro Leu Asn Glu Asn Gly Asn
50 55 60
Ile Phe Asn Leu Glu Ile Lys Thr Lys Leu Asp Leu Ala Thr Lys Ile
65 70 75 80
Ala Ser Leu Asn Thr Ala Ile Gln Asn Asn Phe Ser Asn Ile Arg Met
85 90 95
Thr Asn Tyr Ser Ile Ser Asn Glu Glu Ala Gln Lys Leu Ile Phe Asn
100 105 110
Ala Ile Leu Ser Val Gly Ile Ala Leu Ile Phe Val Thr Ile Phe Thr
115 120 125
Leu Ile Arg Phe Lys Trp Thr Phe Ser Leu Ala Ile Ile Phe Ser Leu
130 135 140
Leu Phe Asn Val Leu Met Val Leu Leu Ala Ile Ile Ile Thr Arg Ile
145 150 155 160
Glu Ile Ser Gln Asn Leu Val Val Ala Ile Leu Thr Leu Ile Gly Tyr
165 170 175
Thr Val Asn Asp Thr Ile Val Val Phe Asp Arg Val Lys Ala Arg Phe
180 185 190
Ser Glu Ile Asn His Glu Asn Val Tyr Lys Phe Asp Lys Ile Lys Glu
195 200 205
Ile Ser Leu Gln Ala Ile Arg Glu Thr Ala Lys Arg Ser Val Tyr Thr
210 215 220
Ser Leu Thr Thr Ile Leu Thr Ile Val Val Leu Met Ile Phe Tyr Glu
225 230 235 240
Ser Ile Asp Ile Val Phe Ser Leu Thr Met Leu Ile Gly Val Ile Ile
245 250 255
Gly Thr Tyr Ser Ser Leu Phe Ile Ala Thr Arg Ile Trp Ile Ile Leu
260 265 270
Glu Ser Ser Arg Asn Arg Lys
275
<210> 29
<211> 2523
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD742
<400> 29
atgaagttaa taaaaattga aattgaaggt tttaaatcct ttgctgaacc tgtaagtatt 60
aaatttgatg gttcaattgt tggaataatt gggccaaatg gctctggaaa atccaatata 120
aatgatgcaa ttaaatgagt tttaggcgaa aaatcagtta aacaattacc gggcccaaat 180
atggatgatg gcatttttgc tggctcaaaa acaggtatga tcgcaattga aaaaattgaa 240
atcaggacaa aagagcttga aaaacaagta aaacagcttg aaaaacaagc agaaaatgca 300
aaaatttacc tcgaaaaatc aaagcaatta gaatctgttg aagtcggctt aattgtctct 360
gatattaaaa agtaccaaac agaattagat caagtccagg aaaaattaaa tgatctaaaa 420
tttcaagaac ctaaatttat cagcgaaatt gaagcaaatg agaaaataat tattacaaat 480
acacaaaaaa ggtcagaaat tgaagctgaa atcaacacta aaaaccgcga aattcaccgc 540
ctaaaagagc aaattaatac cctaaattta gcttatgcaa aagcaactca acttcaagaa 600
atgattttat caagtgaaat tagtgtaaat tttgagcaaa aaatggctgc tttgcgccaa 660
aaatatagtc ttataagcgc gcaaaaagac aattttgcaa aattaatcag ccaaaacaag 720
ctcaaaaaac tagaaattga agaaaaactt aatacattta ggacacaaaa gggtgaaatt 780
gaaaggaatt tatacagtct aaattccgaa aaaattatta gtcaaactag aatctccgag 840
ctaaaaaagt ccttagaatc aatgtctttt ttgccaaagg ggacaaaaat cattatcgaa 900
aatagctttc tttttcctgg atattgtggg cttgtctctg atttaatcaa aattttccca 960
aaatatacag gcgcaattga agccgcattg ggtccaactt taaaacaaat tgttgttgac 1020
caacctgaaa ccgcagtttc agcaattaat tttctaaaga aaaattatgc aggaagcgca 1080
acatttatcc ccctttcaac attaaaaccg cgatttattc ccgatttata tcttgaacat 1140
ctaaattcac aaaaaggttt tataaattta gctagcaatt tagtcgattt tgaaaaaaaa 1200
tacaagattt tagcggattt tttactagga gggattattg ttgctgatac aattgattca 1260
gcaaatcgaa tcgcaaactt ccttaaccac aaaaacatga tcgtaacttt agacggcgat 1320
gttattagaa ctagcgggat aatttctggg ggtcataaga taaaaaatga ttcttccttt 1380
tcaattcagt ataaaatcga tgaactaaca aataatttga atttttttga agaaaaaatt 1440
caagaattta aagttaaatc taatgaattt gaacagttaa ttacaagaga atctgtattt 1500
ttacagcaaa ttaatattaa tcttaatgat ttagagcaaa aatttagtaa ttctgaaaat 1560
gaattaatcg aaattaaagc tcaaaatgaa ggtcttgaag agagtctaaa tcaaaaagat 1620
gacctaaatt taagtctaaa tcgaacttta aaagaaaaaa ttgaacttga aaatgtggtt 1680
ttagaacttg aaaatcaatg caaaatttta aaaactgaaa aaaaacagct cgataatcaa 1740
atttcagaac ttacagtttt agttcaagaa cttaaccaaa aacagcgaaa aatcaacgca 1800
gatcttaacc aaaatcaaaa ttacaaagac aaatatgaat ttttaattac aaatttacga 1860
aataatttat cccaaaaata cagtctaact tttgaaggcg cagctcaaaa atatgaactt 1920
gaaattccag aaaaagatgc tcgcgaattt gttaatagtc taaatttaga gattaaagcg 1980
cttggaaatg ttaatttaga tgcaattaat gactttgaaa caacgagtca aagactcgaa 2040
aaactaaaaa aaagtcaaaa tgaacttgaa actgccaggt caaaaatttt agaagttatc 2100
tcggatttag ataaaattat cattggaaaa acccaggaaa ttgtcgatct agttaattcc 2160
gagtttaacc ttgttttcca gaatatgttt ggtgggggaa gtgcaaaaat ttattttagt 2220
gataaaaacg atattttaaa ttcggggatt gaaataagtg cccaaccacc tggaaaaact 2280
atcaaaaata ttaggctttt ttctgggggc gaaaaggcaa ttattgcaat ttcacttttg 2340
ttttcaatta ttaaggcaag accaattccg ctttgcattc ttgatgaagt tgaagctgcc 2400
cttgatgagt caaatgtgat cagatatgtg gaatttcgaa agcagttaaa acaaaaaacg 2460
cagtttttga tcatcaccca tcggcacgga acgatgtccc gagttgatca acttttagga 2520
atc 2523
<210> 30
<211> 841
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD742
<400> 30
Met Lys Leu Ile Lys Ile Glu Ile Glu Gly Phe Lys Ser Phe Ala Glu
1 5 10 15
Pro Val Ser Ile Lys Phe Asp Gly Ser Ile Val Gly Ile Ile Gly Pro
20 25 30
Asn Gly Ser Gly Lys Ser Asn Ile Asn Asp Ala Ile Lys Trp Val Leu
35 40 45
Gly Glu Lys Ser Val Lys Gln Leu Pro Gly Pro Asn Met Asp Asp Gly
50 55 60
Ile Phe Ala Gly Ser Lys Thr Gly Met Ile Ala Ile Glu Lys Ile Glu
65 70 75 80
Ile Arg Thr Lys Glu Leu Glu Lys Gln Val Lys Gln Leu Glu Lys Gln
85 90 95
Ala Glu Asn Ala Lys Ile Tyr Leu Glu Lys Ser Lys Gln Leu Glu Ser
100 105 110
Val Glu Val Gly Leu Ile Val Ser Asp Ile Lys Lys Tyr Gln Thr Glu
115 120 125
Leu Asp Gln Val Gln Glu Lys Leu Asn Asp Leu Lys Phe Gln Glu Pro
130 135 140
Lys Phe Ile Ser Glu Ile Glu Ala Asn Glu Lys Ile Ile Ile Thr Asn
145 150 155 160
Thr Gln Lys Arg Ser Glu Ile Glu Ala Glu Ile Asn Thr Lys Asn Arg
165 170 175
Glu Ile His Arg Leu Lys Glu Gln Ile Asn Thr Leu Asn Leu Ala Tyr
180 185 190
Ala Lys Ala Thr Gln Leu Gln Glu Met Ile Leu Ser Ser Glu Ile Ser
195 200 205
Val Asn Phe Glu Gln Lys Met Ala Ala Leu Arg Gln Lys Tyr Ser Leu
210 215 220
Ile Ser Ala Gln Lys Asp Asn Phe Ala Lys Leu Ile Ser Gln Asn Lys
225 230 235 240
Leu Lys Lys Leu Glu Ile Glu Glu Lys Leu Asn Thr Phe Arg Thr Gln
245 250 255
Lys Gly Glu Ile Glu Arg Asn Leu Tyr Ser Leu Asn Ser Glu Lys Ile
260 265 270
Ile Ser Gln Thr Arg Ile Ser Glu Leu Lys Lys Ser Leu Glu Ser Met
275 280 285
Ser Phe Leu Pro Lys Gly Thr Lys Ile Ile Ile Glu Asn Ser Phe Leu
290 295 300
Phe Pro Gly Tyr Cys Gly Leu Val Ser Asp Leu Ile Lys Ile Phe Pro
305 310 315 320
Lys Tyr Thr Gly Ala Ile Glu Ala Ala Leu Gly Pro Thr Leu Lys Gln
325 330 335
Ile Val Val Asp Gln Pro Glu Thr Ala Val Ser Ala Ile Asn Phe Leu
340 345 350
Lys Lys Asn Tyr Ala Gly Ser Ala Thr Phe Ile Pro Leu Ser Thr Leu
355 360 365
Lys Pro Arg Phe Ile Pro Asp Leu Tyr Leu Glu His Leu Asn Ser Gln
370 375 380
Lys Gly Phe Ile Asn Leu Ala Ser Asn Leu Val Asp Phe Glu Lys Lys
385 390 395 400
Tyr Lys Ile Leu Ala Asp Phe Leu Leu Gly Gly Ile Ile Val Ala Asp
405 410 415
Thr Ile Asp Ser Ala Asn Arg Ile Ala Asn Phe Leu Asn His Lys Asn
420 425 430
Met Ile Val Thr Leu Asp Gly Asp Val Ile Arg Thr Ser Gly Ile Ile
435 440 445
Ser Gly Gly His Lys Ile Lys Asn Asp Ser Ser Phe Ser Ile Gln Tyr
450 455 460
Lys Ile Asp Glu Leu Thr Asn Asn Leu Asn Phe Phe Glu Glu Lys Ile
465 470 475 480
Gln Glu Phe Lys Val Lys Ser Asn Glu Phe Glu Gln Leu Ile Thr Arg
485 490 495
Glu Ser Val Phe Leu Gln Gln Ile Asn Ile Asn Leu Asn Asp Leu Glu
500 505 510
Gln Lys Phe Ser Asn Ser Glu Asn Glu Leu Ile Glu Ile Lys Ala Gln
515 520 525
Asn Glu Gly Leu Glu Glu Ser Leu Asn Gln Lys Asp Asp Leu Asn Leu
530 535 540
Ser Leu Asn Arg Thr Leu Lys Glu Lys Ile Glu Leu Glu Asn Val Val
545 550 555 560
Leu Glu Leu Glu Asn Gln Cys Lys Ile Leu Lys Thr Glu Lys Lys Gln
565 570 575
Leu Asp Asn Gln Ile Ser Glu Leu Thr Val Leu Val Gln Glu Leu Asn
580 585 590
Gln Lys Gln Arg Lys Ile Asn Ala Asp Leu Asn Gln Asn Gln Asn Tyr
595 600 605
Lys Asp Lys Tyr Glu Phe Leu Ile Thr Asn Leu Arg Asn Asn Leu Ser
610 615 620
Gln Lys Tyr Ser Leu Thr Phe Glu Gly Ala Ala Gln Lys Tyr Glu Leu
625 630 635 640
Glu Ile Pro Glu Lys Asp Ala Arg Glu Phe Val Asn Ser Leu Asn Leu
645 650 655
Glu Ile Lys Ala Leu Gly Asn Val Asn Leu Asp Ala Ile Asn Asp Phe
660 665 670
Glu Thr Thr Ser Gln Arg Leu Glu Lys Leu Lys Lys Ser Gln Asn Glu
675 680 685
Leu Glu Thr Ala Arg Ser Lys Ile Leu Glu Val Ile Ser Asp Leu Asp
690 695 700
Lys Ile Ile Ile Gly Lys Thr Gln Glu Ile Val Asp Leu Val Asn Ser
705 710 715 720
Glu Phe Asn Leu Val Phe Gln Asn Met Phe Gly Gly Gly Ser Ala Lys
725 730 735
Ile Tyr Phe Ser Asp Lys Asn Asp Ile Leu Asn Ser Gly Ile Glu Ile
740 745 750
Ser Ala Gln Pro Pro Gly Lys Thr Ile Lys Asn Ile Arg Leu Phe Ser
755 760 765
Gly Gly Glu Lys Ala Ile Ile Ala Ile Ser Leu Leu Phe Ser Ile Ile
770 775 780
Lys Ala Arg Pro Ile Pro Leu Cys Ile Leu Asp Glu Val Glu Ala Ala
785 790 795 800
Leu Asp Glu Ser Asn Val Ile Arg Tyr Val Glu Phe Arg Lys Gln Leu
805 810 815
Lys Gln Lys Thr Gln Phe Leu Ile Ile Thr His Arg His Gly Thr Met
820 825 830
Ser Arg Val Asp Gln Leu Leu Gly Ile
835 840
<210> 31
<211> 1698
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD760
<400> 31
atgaatagaa aaaaaaccga aaaatcaaaa attagttcaa aagatagtaa aaaattaata 60
attcaagcta tccaagatgt ggcaaaaaat agcgaattaa atctggaagc agttattgat 120
atttttcagg aagcaattga atttgtaata acaaagaaaa ttgacccaga tgcgcaaata 180
aaaattgaag ctgatcttga acaattgagt tttaaagttt ttaatacaaa cgggattgtt 240
gttgaagaaa attattttga tgatcttaca gatgaggaaa aagttaacga tcttgtttct 300
tttattttac tatcaaaggc aaaagaaact gatcctgaga ttcaggttga tgatattttt 360
tcaattgaaa ttaatcttga aagttttgaa cattgacttt ttatggcaat tatgcacgct 420
tttaagcaaa aaatttctga aattgtccga aataatgttt ataacaaata tttatcgctt 480
aaaaataacg tagttttggc cactgttact aataaaattg ctgctggtta tattttcgaa 540
attgacgatg ataaagtttc tgcctttatg ccaagccatt atgcaagtgg acaaaattta 600
aaaataggca ctaaacatga agttgtaatt gaaaatgtat caaaaaatac aaaacagtcg 660
caggttgtga tatcctcaaa atcagttcaa cttgtcaaga aaaaaataat cgatgcaatc 720
cctgaactac agtcaaaatt tcttgaaatc acttcaattg cacggattcc aggggaaaga 780
tgtaaagtcg caattcgcag aaatgaagat gccgaagctg ataatatttc tgaaatcggc 840
tcaattgtag gagcaactgg ctcaagagtt cttgcaattt ctcaagaact tcaaggtgaa 900
aaaattgagg tgattaaata tgatgataat attgtcaaat ttattgttaa tgcgatgtcg 960
ccttcaaaag ttatttgcgt aaaagagttc aaaataggtc ataaattacg tcgttttatc 1020
gtagttgttc ctgattttca acatagttta gccattggaa aaaacggttc aaatgttaaa 1080
ctagtagcag atctaacacg ttgtcaagtg caaattatcc cgtattcaag cgcgctaaaa 1140
gatcaaaatt ttaaaattga atgaaatgga aatattaaag acattcaaga actaaacagt 1200
cttaacaatg agtatattca tcgccagcag ggtagaattt atcaaaatca tcggaattca 1260
tatggtcaag gtaataataa ttttgactta attttacagc aattcgaatc tgatattcgc 1320
gagttagaaa aaccttatgg gattgaaaac gagtttatac caaaaaatga gcaaaaacag 1380
gtaagaagtc accaagaatt tccaaaaaac aagaataatc tagcaaaagc agcaactaaa 1440
tcgcgtaatt ttaacaaaag ccagaatatc cgcgaaaata tttcaaaaga ttttgattat 1500
ggctttgaaa acgagaaaga ttctaattct ttccaaaata ttagtcaaag atcttttttt 1560
gatgcagatt cactttttga ttcggctcta aatgaggcaa ttagtgaaaa cgagttaatc 1620
gataaaattc accaagaaga ggaaaaaaaa caagaattat tattacaaga gaaggaaaaa 1680
tgagcaaaaa atgaagct 1698
<210> 32
<211> 566
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD760
<400> 32
Met Asn Arg Lys Lys Thr Glu Lys Ser Lys Ile Ser Ser Lys Asp Ser
1 5 10 15
Lys Lys Leu Ile Ile Gln Ala Ile Gln Asp Val Ala Lys Asn Ser Glu
20 25 30
Leu Asn Leu Glu Ala Val Ile Asp Ile Phe Gln Glu Ala Ile Glu Phe
35 40 45
Val Ile Thr Lys Lys Ile Asp Pro Asp Ala Gln Ile Lys Ile Glu Ala
50 55 60
Asp Leu Glu Gln Leu Ser Phe Lys Val Phe Asn Thr Asn Gly Ile Val
65 70 75 80
Val Glu Glu Asn Tyr Phe Asp Asp Leu Thr Asp Glu Glu Lys Val Asn
85 90 95
Asp Leu Val Ser Phe Ile Leu Leu Ser Lys Ala Lys Glu Thr Asp Pro
100 105 110
Glu Ile Gln Val Asp Asp Ile Phe Ser Ile Glu Ile Asn Leu Glu Ser
115 120 125
Phe Glu His Trp Leu Phe Met Ala Ile Met His Ala Phe Lys Gln Lys
130 135 140
Ile Ser Glu Ile Val Arg Asn Asn Val Tyr Asn Lys Tyr Leu Ser Leu
145 150 155 160
Lys Asn Asn Val Val Leu Ala Thr Val Thr Asn Lys Ile Ala Ala Gly
165 170 175
Tyr Ile Phe Glu Ile Asp Asp Asp Lys Val Ser Ala Phe Met Pro Ser
180 185 190
His Tyr Ala Ser Gly Gln Asn Leu Lys Ile Gly Thr Lys His Glu Val
195 200 205
Val Ile Glu Asn Val Ser Lys Asn Thr Lys Gln Ser Gln Val Val Ile
210 215 220
Ser Ser Lys Ser Val Gln Leu Val Lys Lys Lys Ile Ile Asp Ala Ile
225 230 235 240
Pro Glu Leu Gln Ser Lys Phe Leu Glu Ile Thr Ser Ile Ala Arg Ile
245 250 255
Pro Gly Glu Arg Cys Lys Val Ala Ile Arg Arg Asn Glu Asp Ala Glu
260 265 270
Ala Asp Asn Ile Ser Glu Ile Gly Ser Ile Val Gly Ala Thr Gly Ser
275 280 285
Arg Val Leu Ala Ile Ser Gln Glu Leu Gln Gly Glu Lys Ile Glu Val
290 295 300
Ile Lys Tyr Asp Asp Asn Ile Val Lys Phe Ile Val Asn Ala Met Ser
305 310 315 320
Pro Ser Lys Val Ile Cys Val Lys Glu Phe Lys Ile Gly His Lys Leu
325 330 335
Arg Arg Phe Ile Val Val Val Pro Asp Phe Gln His Ser Leu Ala Ile
340 345 350
Gly Lys Asn Gly Ser Asn Val Lys Leu Val Ala Asp Leu Thr Arg Cys
355 360 365
Gln Val Gln Ile Ile Pro Tyr Ser Ser Ala Leu Lys Asp Gln Asn Phe
370 375 380
Lys Ile Glu Trp Asn Gly Asn Ile Lys Asp Ile Gln Glu Leu Asn Ser
385 390 395 400
Leu Asn Asn Glu Tyr Ile His Arg Gln Gln Gly Arg Ile Tyr Gln Asn
405 410 415
His Arg Asn Ser Tyr Gly Gln Gly Asn Asn Asn Phe Asp Leu Ile Leu
420 425 430
Gln Gln Phe Glu Ser Asp Ile Arg Glu Leu Glu Lys Pro Tyr Gly Ile
435 440 445
Glu Asn Glu Phe Ile Pro Lys Asn Glu Gln Lys Gln Val Arg Ser His
450 455 460
Gln Glu Phe Pro Lys Asn Lys Asn Asn Leu Ala Lys Ala Ala Thr Lys
465 470 475 480
Ser Arg Asn Phe Asn Lys Ser Gln Asn Ile Arg Glu Asn Ile Ser Lys
485 490 495
Asp Phe Asp Tyr Gly Phe Glu Asn Glu Lys Asp Ser Asn Ser Phe Gln
500 505 510
Asn Ile Ser Gln Arg Ser Phe Phe Asp Ala Asp Ser Leu Phe Asp Ser
515 520 525
Ala Leu Asn Glu Ala Ile Ser Glu Asn Glu Leu Ile Asp Lys Ile His
530 535 540
Gln Glu Glu Glu Lys Lys Gln Glu Leu Leu Leu Gln Glu Lys Glu Lys
545 550 555 560
Trp Ala Lys Asn Glu Ala
565
<210> 33
<211> 1860
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD774
<400> 33
gaattctacc tttgatcacc taatgcaaat cgggtacatt ttgcaattta taaagatccg 60
gaagacaaaa ttccggctga aattattgtg atgtcaaaaa ataatgatgt ttggttttgc 120
caaattaatg cctcttttaa tggatattcc tataatttat taattgagca tcacgattta 180
aaaataactg aggcacttga tccttatgcc tttagtattg cgccttttga ttgaaaaaaa 240
aatgaaagtc caaaagcata tttaattgac attttttccg aaaaaactgg aaaaaatcct 300
tcaaaattag aaggatttaa caaaaatccg caaattgatg ctcaaattta tcagctgcac 360
attcgagatt tttcatctat tagtaaaaaa acagaaaata aaggtacttt tatcggagcg 420
ctagaaaatg atgtttttag ttatttaaat agcttaaaat ttaatttttt acaattatta 480
ccaatccact cttgttataa tttcagccaa aaaaacgcta gcatcctcca caaaggggat 540
ggaaacggtc attttagcac ttataattgg ggttatgacc caattggtta cttttcgata 600
aattcaagtt attcaacaga tccaatggat ccatatctgc gaatttttga gtttaaaaaa 660
tttgttgact ccgcccataa aaataagatc ggaattgttc ttgatgttga ttttagtcac 720
acctttaaaa attcaattct tgaggatgta gctcacgggc atttttaccg ggatgaagca 780
gctgttttac ctgccggatt tccgccactt gatacacgaa aaccaatggc atttaggcta 840
attttggatt ccttaatttt ttttactaaa tattataaag ttgatggatt tcgctttaat 900
ttagcatctt ttttagataa aaaagcaatt acagttattg ccagtgaact aaaaaaagtt 960
aatccaaata ttcttttata tggtgatttt tcaaatccta gtgacctacc aagcagaaat 1020
cgacttgaaa aagggaaaac aggaaatagt tttaactttg gatatttaaa cgatacaatc 1080
caaacagcaa ttatcgggag cggaaatccg cgtgataaag gtttaatttt atcaaaaact 1140
agtaaaaaat tcgctgctta tgtttcttca attccgggga acattgcaaa ttttgacttc 1200
caaaatttgc catattcaaa aaaaaaatac gacctttttg caaacgatat cagcctaaat 1260
cttgcctatc ttacttgtta taatggcccg actttagccg ataaaattct tagtgcgaca 1320
acgcgaattg gaaaaagaga atttcttgaa atctaccggc aagccttaat gatggtcaat 1380
tttgtccaag gaaaaatttc acttagtgct gggactgaat ttgctttttc aagaatttgt 1440
gatttttctg ggggcagtta tcaaaattgc tatcctaatt taaacataaa aagaccgcct 1500
ttttcgtttt tagcgggcaa atatcttgat tttcattctg ataaaaccac agatttcaca 1560
aatggattga attttgaaat tcttaaaaac aatgaaatca aagagaaaat ctttgatttt 1620
cttgccgaaa ttaatcaatt tcgccaaaat tctccatttt ttcggcttga tacaaaccaa 1680
aaaatcaaaa aacagctaaa atttgaaact gttgataaca ataaaggatt aattatcttt 1740
aaaattctgc taaaaataaa gtgattaaag ttattcataa tttttcacat ctttcttatg 1800
aatatgattt taaaaatttt aatattcttt ttagctcaaa gattaaagtt attcctaatt 1860
1860
<210> 34
<211> 620
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD774
<400> 34
Glu Phe Tyr Leu Trp Ser Pro Asn Ala Asn Arg Val His Phe Ala Ile
1 5 10 15
Tyr Lys Asp Pro Glu Asp Lys Ile Pro Ala Glu Ile Ile Val Met Ser
20 25 30
Lys Asn Asn Asp Val Trp Phe Cys Gln Ile Asn Ala Ser Phe Asn Gly
35 40 45
Tyr Ser Tyr Asn Leu Leu Ile Glu His His Asp Leu Lys Ile Thr Glu
50 55 60
Ala Leu Asp Pro Tyr Ala Phe Ser Ile Ala Pro Phe Asp Trp Lys Lys
65 70 75 80
Asn Glu Ser Pro Lys Ala Tyr Leu Ile Asp Ile Phe Ser Glu Lys Thr
85 90 95
Gly Lys Asn Pro Ser Lys Leu Glu Gly Phe Asn Lys Asn Pro Gln Ile
100 105 110
Asp Ala Gln Ile Tyr Gln Leu His Ile Arg Asp Phe Ser Ser Ile Ser
115 120 125
Lys Lys Thr Glu Asn Lys Gly Thr Phe Ile Gly Ala Leu Glu Asn Asp
130 135 140
Val Phe Ser Tyr Leu Asn Ser Leu Lys Phe Asn Phe Leu Gln Leu Leu
145 150 155 160
Pro Ile His Ser Cys Tyr Asn Phe Ser Gln Lys Asn Ala Ser Ile Leu
165 170 175
His Lys Gly Asp Gly Asn Gly His Phe Ser Thr Tyr Asn Trp Gly Tyr
180 185 190
Asp Pro Ile Gly Tyr Phe Ser Ile Asn Ser Ser Tyr Ser Thr Asp Pro
195 200 205
Met Asp Pro Tyr Leu Arg Ile Phe Glu Phe Lys Lys Phe Val Asp Ser
210 215 220
Ala His Lys Asn Lys Ile Gly Ile Val Leu Asp Val Asp Phe Ser His
225 230 235 240
Thr Phe Lys Asn Ser Ile Leu Glu Asp Val Ala His Gly His Phe Tyr
245 250 255
Arg Asp Glu Ala Ala Val Leu Pro Ala Gly Phe Pro Pro Leu Asp Thr
260 265 270
Arg Lys Pro Met Ala Phe Arg Leu Ile Leu Asp Ser Leu Ile Phe Phe
275 280 285
Thr Lys Tyr Tyr Lys Val Asp Gly Phe Arg Phe Asn Leu Ala Ser Phe
290 295 300
Leu Asp Lys Lys Ala Ile Thr Val Ile Ala Ser Glu Leu Lys Lys Val
305 310 315 320
Asn Pro Asn Ile Leu Leu Tyr Gly Asp Phe Ser Asn Pro Ser Asp Leu
325 330 335
Pro Ser Arg Asn Arg Leu Glu Lys Gly Lys Thr Gly Asn Ser Phe Asn
340 345 350
Phe Gly Tyr Leu Asn Asp Thr Ile Gln Thr Ala Ile Ile Gly Ser Gly
355 360 365
Asn Pro Arg Asp Lys Gly Leu Ile Leu Ser Lys Thr Ser Lys Lys Phe
370 375 380
Ala Ala Tyr Val Ser Ser Ile Pro Gly Asn Ile Ala Asn Phe Asp Phe
385 390 395 400
Gln Asn Leu Pro Tyr Ser Lys Lys Lys Tyr Asp Leu Phe Ala Asn Asp
405 410 415
Ile Ser Leu Asn Leu Ala Tyr Leu Thr Cys Tyr Asn Gly Pro Thr Leu
420 425 430
Ala Asp Lys Ile Leu Ser Ala Thr Thr Arg Ile Gly Lys Arg Glu Phe
435 440 445
Leu Glu Ile Tyr Arg Gln Ala Leu Met Met Val Asn Phe Val Gln Gly
450 455 460
Lys Ile Ser Leu Ser Ala Gly Thr Glu Phe Ala Phe Ser Arg Ile Cys
465 470 475 480
Asp Phe Ser Gly Gly Ser Tyr Gln Asn Cys Tyr Pro Asn Leu Asn Ile
485 490 495
Lys Arg Pro Pro Phe Ser Phe Leu Ala Gly Lys Tyr Leu Asp Phe His
500 505 510
Ser Asp Lys Thr Thr Asp Phe Thr Asn Gly Leu Asn Phe Glu Ile Leu
515 520 525
Lys Asn Asn Glu Ile Lys Glu Lys Ile Phe Asp Phe Leu Ala Glu Ile
530 535 540
Asn Gln Phe Arg Gln Asn Ser Pro Phe Phe Arg Leu Asp Thr Asn Gln
545 550 555 560
Lys Ile Lys Lys Gln Leu Lys Phe Glu Thr Val Asp Asn Asn Lys Gly
565 570 575
Leu Ile Ile Phe Lys Ile Leu Leu Lys Ile Lys Trp Leu Lys Leu Phe
580 585 590
Ile Ile Phe His Ile Phe Leu Met Asn Met Ile Leu Lys Ile Leu Ile
595 600 605
Phe Phe Leu Ala Gln Arg Leu Lys Leu Phe Leu Ile
610 615 620
<210> 35
<211> 897
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD784
<400> 35
gcttttttgt ttgttgatgg tcggtatatt gaaaaagctg aaaaagatgc taaaaattgt 60
caggtttttt tacctaccaa gcaaatcttg aagatttttt caagaaaacc cgtatcaaaa 120
aatcggcatt gatctgaata tttaactatt gaccaatttg ataaaataag aagttgattt 180
ccaaatgccg attttgttaa gttacaagcc caactttttc gaattataaa aacagaagaa 240
gaaatcaaaa atatcgaaaa agctgttgaa atctcactcg cggcttataa taaaatattt 300
ccaaaaatca aaccgggaat gacggagaaa agtatcgatg tcaacctaaa ttatcaaatg 360
aagcttttag gagccgaaaa agaatccttt gattcaataa ttgcaactgg ttctaattcg 420
gcaatgccgc attgaagggc gagtgaaacc gaaattttag ataatgatct tttaaaaatt 480
gattttggtg cgctttttaa cggttattgc gctgatatta caagaacttc ttatcttgga 540
cagattagtg aaaaaaaatt agaaattttg gaaatagtaa aaaaagctgc tgaaattggt 600
agaaaaaaag ttgctcctgg ggttaaagcc agcgaaattg accttgcttg ccggaatttt 660
atcaccgaac aaggctatgg aaaatatttt attcactcaa ctggccacgg ggttggtatt 720
gatatccatg aattgccagt tgttagttca actagccaga caattttaga gcccggaatg 780
gtaataactg ttgaacccgg aatttatatc cctggacttg gaggcgcaag aattgaggat 840
gttgttttag taactgaaag tggttttcgt accttgtcac gaaaaggtga aagaatt 897
<210> 36
<211> 299
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD784
<400> 36
Ala Phe Leu Phe Val Asp Gly Arg Tyr Ile Glu Lys Ala Glu Lys Asp
1 5 10 15
Ala Lys Asn Cys Gln Val Phe Leu Pro Thr Lys Gln Ile Leu Lys Ile
20 25 30
Phe Ser Arg Lys Pro Val Ser Lys Asn Arg His Trp Ser Glu Tyr Leu
35 40 45
Thr Ile Asp Gln Phe Asp Lys Ile Arg Ser Trp Phe Pro Asn Ala Asp
50 55 60
Phe Val Lys Leu Gln Ala Gln Leu Phe Arg Ile Ile Lys Thr Glu Glu
65 70 75 80
Glu Ile Lys Asn Ile Glu Lys Ala Val Glu Ile Ser Leu Ala Ala Tyr
85 90 95
Asn Lys Ile Phe Pro Lys Ile Lys Pro Gly Met Thr Glu Lys Ser Ile
100 105 110
Asp Val Asn Leu Asn Tyr Gln Met Lys Leu Leu Gly Ala Glu Lys Glu
115 120 125
Ser Phe Asp Ser Ile Ile Ala Thr Gly Ser Asn Ser Ala Met Pro His
130 135 140
Trp Arg Ala Ser Glu Thr Glu Ile Leu Asp Asn Asp Leu Leu Lys Ile
145 150 155 160
Asp Phe Gly Ala Leu Phe Asn Gly Tyr Cys Ala Asp Ile Thr Arg Thr
165 170 175
Ser Tyr Leu Gly Gln Ile Ser Glu Lys Lys Leu Glu Ile Leu Glu Ile
180 185 190
Val Lys Lys Ala Ala Glu Ile Gly Arg Lys Lys Val Ala Pro Gly Val
195 200 205
Lys Ala Ser Glu Ile Asp Leu Ala Cys Arg Asn Phe Ile Thr Glu Gln
210 215 220
Gly Tyr Gly Lys Tyr Phe Ile His Ser Thr Gly His Gly Val Gly Ile
225 230 235 240
Asp Ile His Glu Leu Pro Val Val Ser Ser Thr Ser Gln Thr Ile Leu
245 250 255
Glu Pro Gly Met Val Ile Thr Val Glu Pro Gly Ile Tyr Ile Pro Gly
260 265 270
Leu Gly Gly Ala Arg Ile Glu Asp Val Val Leu Val Thr Glu Ser Gly
275 280 285
Phe Arg Thr Leu Ser Arg Lys Gly Glu Arg Ile
290 295
<210> 37
<211> 633
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD789
<400> 37
gatcttgtat ttaaagtaga aaattctgaa aatcaattac aagatttaga tggaactttt 60
tctttaatta gtattaaaaa tttaaactat aaattggaag atagagtttt atttaataat 120
ttaaatttag aagttcaaaa aggtaaaaaa tatttactaa aaggagctaa cgggtctgga 180
aagtccacat tttcaaggat tttattaggc attgagaagg aatttgaagg tcaaatttta 240
ataaataaca aatacgatat aaaaaaaata aatcctgatt ctataaataa ccatattaat 300
tatgtataca acaattcaga cttaattaat gcatcaactc tagaaaatat ttcgcttttg 360
gaaccgaaaa caaaagatga gattaggccg ttattagaaa aggtaaattt tgaaaacctt 420
gatttagaca agaaaattga ttctgatgtt tgattatttt tccactgggc aaatccaaaa 480
aatccccttg cacgctcact ttattctcca aaagaaattt taataattga cgaaggtctt 540
tccaacttag accaagaaag ttatgttaaa atcatatctg aacttattgc ggataaaaat 600
ttaacattaa ttttcattac ccctcacttt gat 633
<210> 38
<211> 211
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD789
<400> 38
Asp Leu Val Phe Lys Val Glu Asn Ser Glu Asn Gln Leu Gln Asp Leu
1 5 10 15
Asp Gly Thr Phe Ser Leu Ile Ser Ile Lys Asn Leu Asn Tyr Lys Leu
20 25 30
Glu Asp Arg Val Leu Phe Asn Asn Leu Asn Leu Glu Val Gln Lys Gly
35 40 45
Lys Lys Tyr Leu Leu Lys Gly Ala Asn Gly Ser Gly Lys Ser Thr Phe
50 55 60
Ser Arg Ile Leu Leu Gly Ile Glu Lys Glu Phe Glu Gly Gln Ile Leu
65 70 75 80
Ile Asn Asn Lys Tyr Asp Ile Lys Lys Ile Asn Pro Asp Ser Ile Asn
85 90 95
Asn His Ile Asn Tyr Val Tyr Asn Asn Ser Asp Leu Ile Asn Ala Ser
100 105 110
Thr Leu Glu Asn Ile Ser Leu Leu Glu Pro Lys Thr Lys Asp Glu Ile
115 120 125
Arg Pro Leu Leu Glu Lys Val Asn Phe Glu Asn Leu Asp Leu Asp Lys
130 135 140
Lys Ile Asp Ser Asp Val Trp Leu Phe Phe His Trp Ala Asn Pro Lys
145 150 155 160
Asn Pro Leu Ala Arg Ser Leu Tyr Ser Pro Lys Glu Ile Leu Ile Ile
165 170 175
Asp Glu Gly Leu Ser Asn Leu Asp Gln Glu Ser Tyr Val Lys Ile Ile
180 185 190
Ser Glu Leu Ile Ala Asp Lys Asn Leu Thr Leu Ile Phe Ile Thr Pro
195 200 205
His Phe Asp
210
<210> 39
<211> 1791
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clones pAD908, pAD981, pAD1013
, and pAD1049
<400> 39
cttgaaataa tcaaatatgg atcaaaagaa tctctaaatt actgactaat ttctgaaagc 60
gggaaaagat atgactattt tcgaccaatt gaaggaattc ttaataaaat tcagagaaaa 120
ttttgggaga catcaagcga agatttacga ctttgattta agaaaatgat gtcagaattt 180
ccttgtagta gttgcaaagg agcccggctt aacaagtatg cgcttgccgt tttcattgaa 240
aagtataata tctttcaatt atcccaactt tcaattaaag atttaataac tttttttaga 300
aatttaaaat taactgaatt tgacggaaaa atttctactt taattctcga tgaaattaaa 360
tcacgactgt catttttagc aaatgttggt cttgaatatt taactttaaa tagatcaacg 420
gcaaccttat caggaggcga atcccaacga attaggcttg caagccaggt tggatatcaa 480
ctaaccggaa ttctttatgt tcttgatgaa ccttcaattg gcctacatca aaaagataat 540
gacaaattaa ttgcgacact gaaaaaaatg gttgaaattg gtaatagttt aattgtagtc 600
gagcatgatt ttgagacaat tttagctgct gattatattg ttgatatcgg gccaaaagct 660
ggtgaaaacg gtggtttttt ggttgctgca ggatcaatta aggatattga aaatgaacca 720
aaatcactta ccggccaatt tttaactgga aaattggaaa ttccagtacc aaaaaaacga 780
cgggctggca atggcaaatt tataattatt gaaaaagctg ctgaaaataa tttaaaaaaa 840
attaatgtca acattcctct aggcaaattt gttgttgtca ctggtgtttc tggatctgga 900
aagtcgacat tagttaatca aattatcgta aatgcgattg ccaaaaatct tggaacaact 960
aatattcgca ttgggaaaaa tgtgaggaaa ttaaagggct ttttaatatt gataagttga 1020
ttgcaatcaa tcaaagtcaa tcggacgaac cctagatcaa atcccgcaac ttatacctct 1080
gtttttgatg atatccgtga ggtttttgcc aatactgagc aggcaagagc gcttggtttt 1140
tcaaagtcaa aattttcctt taatctgcaa actgggcggt gtgataaatg ccaaggagac 1200
gggcaaatta aaattgaaat gtattttatg cctgatattt atgttttatg tgatcactgc 1260
caaggaaaaa gatacaagcc ggatgtccta caaattcgtt tttatggaaa aacaatcgcg 1320
gatattcttg atttaacagt ttcagaagca cttgaatttt tccataattg gcctaaaata 1380
atcgcaaaat tacaaaccct agctgatgtt ggtcttggtt atataaaact tggccaatca 1440
gcaataactt tatcaggagg agaagctcaa cgaattaaat tagccacttt tttacaaaaa 1500
aaacctaaag gaaaatcact ttttgtactt gacgagccaa caactggact ccataattat 1560
gatgttgcta atttaattaa agtgctaaat cgaatagtcg ataacggtga tagcataatt 1620
gtaatcgagc ataatttaga ggtaattaaa gttgctgact atattattga tttaggccca 1680
aacggcgggg ataacggggg ccaaatagtt gcaaaaggaa caccagaagc tgtagcaaaa 1740
gttagtgaat catatactgg cgcttattta aaaacaattt taaatataaa a 1791
<210> 40
<211> 597
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clones pAD908, pAD981, pAD1013, and pAD1049
<400> 40
Leu Glu Ile Ile Lys Tyr Gly Ser Lys Glu Ser Leu Asn Tyr Trp Leu
1 5 10 15
Ile Ser Glu Ser Gly Lys Arg Tyr Asp Tyr Phe Arg Pro Ile Glu Gly
20 25 30
Ile Leu Asn Lys Ile Gln Arg Lys Phe Trp Glu Thr Ser Ser Glu Asp
35 40 45
Leu Arg Leu Trp Phe Lys Lys Met Met Ser Glu Phe Pro Cys Ser Ser
50 55 60
Cys Lys Gly Ala Arg Leu Asn Lys Tyr Ala Leu Ala Val Phe Ile Glu
65 70 75 80
Lys Tyr Asn Ile Phe Gln Leu Ser Gln Leu Ser Ile Lys Asp Leu Ile
85 90 95
Thr Phe Phe Arg Asn Leu Lys Leu Thr Glu Phe Asp Gly Lys Ile Ser
100 105 110
Thr Leu Ile Leu Asp Glu Ile Lys Ser Arg Leu Ser Phe Leu Ala Asn
115 120 125
Val Gly Leu Glu Tyr Leu Thr Leu Asn Arg Ser Thr Ala Thr Leu Ser
130 135 140
Gly Gly Glu Ser Gln Arg Ile Arg Leu Ala Ser Gln Val Gly Tyr Gln
145 150 155 160
Leu Thr Gly Ile Leu Tyr Val Leu Asp Glu Pro Ser Ile Gly Leu His
165 170 175
Gln Lys Asp Asn Asp Lys Leu Ile Ala Thr Leu Lys Lys Met Val Glu
180 185 190
Ile Gly Asn Ser Leu Ile Val Val Glu His Asp Phe Glu Thr Ile Leu
195 200 205
Ala Ala Asp Tyr Ile Val Asp Ile Gly Pro Lys Ala Gly Glu Asn Gly
210 215 220
Gly Phe Leu Val Ala Ala Gly Ser Ile Lys Asp Ile Glu Asn Glu Pro
225 230 235 240
Lys Ser Leu Thr Gly Gln Phe Leu Thr Gly Lys Leu Glu Ile Pro Val
245 250 255
Pro Lys Lys Arg Arg Ala Gly Asn Gly Lys Phe Ile Ile Ile Glu Lys
260 265 270
Ala Ala Glu Asn Asn Leu Lys Lys Ile Asn Val Asn Ile Pro Leu Gly
275 280 285
Lys Phe Val Val Val Thr Gly Val Ser Gly Ser Gly Lys Ser Thr Leu
290 295 300
Val Asn Gln Ile Ile Val Asn Ala Ile Ala Lys Asn Leu Gly Thr Thr
305 310 315 320
Asn Ile Arg Ile Gly Lys Asn Val Arg Lys Leu Lys Gly Phe Leu Ile
325 330 335
Leu Ile Ser Trp Leu Gln Ser Ile Lys Val Asn Arg Thr Asn Pro Arg
340 345 350
Ser Asn Pro Ala Thr Tyr Thr Ser Val Phe Asp Asp Ile Arg Glu Val
355 360 365
Phe Ala Asn Thr Glu Gln Ala Arg Ala Leu Gly Phe Ser Lys Ser Lys
370 375 380
Phe Ser Phe Asn Leu Gln Thr Gly Arg Cys Asp Lys Cys Gln Gly Asp
385 390 395 400
Gly Gln Ile Lys Ile Glu Met Tyr Phe Met Pro Asp Ile Tyr Val Leu
405 410 415
Cys Asp His Cys Gln Gly Lys Arg Tyr Lys Pro Asp Val Leu Gln Ile
420 425 430
Arg Phe Tyr Gly Lys Thr Ile Ala Asp Ile Leu Asp Leu Thr Val Ser
435 440 445
Glu Ala Leu Glu Phe Phe His Asn Trp Pro Lys Ile Ile Ala Lys Leu
450 455 460
Gln Thr Leu Ala Asp Val Gly Leu Gly Tyr Ile Lys Leu Gly Gln Ser
465 470 475 480
Ala Ile Thr Leu Ser Gly Gly Glu Ala Gln Arg Ile Lys Leu Ala Thr
485 490 495
Phe Leu Gln Lys Lys Pro Lys Gly Lys Ser Leu Phe Val Leu Asp Glu
500 505 510
Pro Thr Thr Gly Leu His Asn Tyr Asp Val Ala Asn Leu Ile Lys Val
515 520 525
Leu Asn Arg Ile Val Asp Asn Gly Asp Ser Ile Ile Val Ile Glu His
530 535 540
Asn Leu Glu Val Ile Lys Val Ala Asp Tyr Ile Ile Asp Leu Gly Pro
545 550 555 560
Asn Gly Gly Asp Asn Gly Gly Gln Ile Val Ala Lys Gly Thr Pro Glu
565 570 575
Ala Val Ala Lys Val Ser Glu Ser Tyr Thr Gly Ala Tyr Leu Lys Thr
580 585 590
Ile Leu Asn Ile Lys
595
<210> 41
<211> 900
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD913
<400> 41
atgaaaatta aagcaaaaac catcgtaaaa atttatgatc aaaaattacc atcagaatta 60
aaagcccttg ataaagtaac tactgaaata aatcagggcg agtttattgc aataattggc 120
caaactggtt caggaaaaac aacttttatt cagcatatga atgcactttt gctaccagat 180
caaggcgaaa ttgagtatct ctattttgat tcaaaaaatc aagaaaaaaa attagttgtt 240
caaaaaccgc gtttttttag aaaaaaacta aaatttatta atgaaattcg tcggcgtgtg 300
ggcgtcgttt ttcagtttgc tgaatatcag ctttttgagc aaacaattga aaaagacatc 360
atatttgggg ctgtttcaat gggaactcca aaaaatgagg caaaaaaaat tgccgcagaa 420
ataattgaat tagttggtct tgatcaaagt tttttacaaa aatcaccttt tgaactttca 480
ggtggccaga aacgccgagt tgcaattgcc ggaattttag caatggatcc tgatattatt 540
ttttttgatg aacccacggc cggacttgat ccccaaggaa cgctaaaaat gcttgaaatt 600
cttgatactt tatataaaaa gggcaagaca atcattctgg caactcatga tcttgatagt 660
gttttagaat gaacaaaacg ttgtattttt tttaaagatg gtagaattat ttatgatggt 720
gatacttatt caattttagc aaataataaa tttttaattg aaaataagat gttaccaact 780
aatttactca attttcgcga aaaattaatc aaaattggtt atccaatttc taatgttaga 840
tcagtatctg agttaatcag tgaaattaat atgctaattc aaaaggaaac aaatgcagat 900
900
<210> 42
<211> 300
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD913
<400> 42
Met Lys Ile Lys Ala Lys Thr Ile Val Lys Ile Tyr Asp Gln Lys Leu
1 5 10 15
Pro Ser Glu Leu Lys Ala Leu Asp Lys Val Thr Thr Glu Ile Asn Gln
20 25 30
Gly Glu Phe Ile Ala Ile Ile Gly Gln Thr Gly Ser Gly Lys Thr Thr
35 40 45
Phe Ile Gln His Met Asn Ala Leu Leu Leu Pro Asp Gln Gly Glu Ile
50 55 60
Glu Tyr Leu Tyr Phe Asp Ser Lys Asn Gln Glu Lys Lys Leu Val Val
65 70 75 80
Gln Lys Pro Arg Phe Phe Arg Lys Lys Leu Lys Phe Ile Asn Glu Ile
85 90 95
Arg Arg Arg Val Gly Val Val Phe Gln Phe Ala Glu Tyr Gln Leu Phe
100 105 110
Glu Gln Thr Ile Glu Lys Asp Ile Ile Phe Gly Ala Val Ser Met Gly
115 120 125
Thr Pro Lys Asn Glu Ala Lys Lys Ile Ala Ala Glu Ile Ile Glu Leu
130 135 140
Val Gly Leu Asp Gln Ser Phe Leu Gln Lys Ser Pro Phe Glu Leu Ser
145 150 155 160
Gly Gly Gln Lys Arg Arg Val Ala Ile Ala Gly Ile Leu Ala Met Asp
165 170 175
Pro Asp Ile Ile Phe Phe Asp Glu Pro Thr Ala Gly Leu Asp Pro Gln
180 185 190
Gly Thr Leu Lys Met Leu Glu Ile Leu Asp Thr Leu Tyr Lys Lys Gly
195 200 205
Lys Thr Ile Ile Leu Ala Thr His Asp Leu Asp Ser Val Leu Glu Trp
210 215 220
Thr Lys Arg Cys Ile Phe Phe Lys Asp Gly Arg Ile Ile Tyr Asp Gly
225 230 235 240
Asp Thr Tyr Ser Ile Leu Ala Asn Asn Lys Phe Leu Ile Glu Asn Lys
245 250 255
Met Leu Pro Thr Asn Leu Leu Asn Phe Arg Glu Lys Leu Ile Lys Ile
260 265 270
Gly Tyr Pro Ile Ser Asn Val Arg Ser Val Ser Glu Leu Ile Ser Glu
275 280 285
Ile Asn Met Leu Ile Gln Lys Glu Thr Asn Ala Asp
290 295 300
<210> 43
<211> 489
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD920
<400> 43
ttaaaatccc gtttttatca aaaagtaaat tcgcagatag acgttaaaaa aaacacagat 60
caagaaaaag ataaaaaaac tgagcccgaa aaaattaatt tttatactct gaaaaaagta 120
atttttcctg aaagtttgct tgagattgat gattatgcct tttatgtcga tagtgcaaat 180
ttagatcaaa atgaaaaaat tcaagaactt gatttttcaa aagcaatgaa attaaggagg 240
attgggagtt tcgcttttca aggaaacaat ataaaaacgc tcgttttacc cccttctatt 300
acatcaattg gaaaacaagc ttttgcaaaa aacagtttag aaacagtaga tttttcccag 360
gcaacaaaac tagaaacaat tgaacctggt gccttttttg ataataaaat caccgaactt 420
gatttgtcaa aaaatttgat tttagccgaa attttcaggg tagttttgag acaaatcaaa 480
ttatcaagt 489
<210> 44
<211> 163
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD920
<400> 44
Leu Lys Ser Arg Phe Tyr Gln Lys Val Asn Ser Gln Ile Asp Val Lys
1 5 10 15
Lys Asn Thr Asp Gln Glu Lys Asp Lys Lys Thr Glu Pro Glu Lys Ile
20 25 30
Asn Phe Tyr Thr Leu Lys Lys Val Ile Phe Pro Glu Ser Leu Leu Glu
35 40 45
Ile Asp Asp Tyr Ala Phe Tyr Val Asp Ser Ala Asn Leu Asp Gln Asn
50 55 60
Glu Lys Ile Gln Glu Leu Asp Phe Ser Lys Ala Met Lys Leu Arg Arg
65 70 75 80
Ile Gly Ser Phe Ala Phe Gln Gly Asn Asn Ile Lys Thr Leu Val Leu
85 90 95
Pro Pro Ser Ile Thr Ser Ile Gly Lys Gln Ala Phe Ala Lys Asn Ser
100 105 110
Leu Glu Thr Val Asp Phe Ser Gln Ala Thr Lys Leu Glu Thr Ile Glu
115 120 125
Pro Gly Ala Phe Phe Asp Asn Lys Ile Thr Glu Leu Asp Leu Ser Lys
130 135 140
Asn Leu Ile Leu Ala Glu Ile Phe Arg Val Val Leu Arg Gln Ile Lys
145 150 155 160
Leu Ser Ser
<210> 45
<211> 1101
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD922
<400> 45
actgatcaga tcttaatttt ccatttggcc aaaactttag accaaaaata tcttgaaatt 60
gaccttgaaa tgctcgaaaa aggtaacttt gaatttcaag atttcattaa tttctggcaa 120
tctcggattg aaaaaataga agaaaattta gcgcaaattt ctaccgataa aatcacagag 180
gcaaaaatca acgaattttt taattcttat ttgctttatt ttgaaaaatt acaaaaatta 240
tttagctcat catataatct tggctatgaa aatgtggcca aattatatga ttatttctat 300
gaagtccaaa aaatttaccg acaaaaacag caagcaaaag tcgaatttga ctaccgcagt 360
gctaaaaaag attatgaaga ccagctaaaa aaaataaagc aagaaaaagc ttttttcatt 420
aaaacattaa atgtaaaagc gcttaattta aaaaaagagg cccaactcga gattgacaaa 480
ttcaccgctc aaaacaattt gttgacttcc tatattgacg aatttaatta tgaatataaa 540
attgcaaata acaaagcgct agtaacaaca gatctaaaaa attattcatt ttttaaaaaa 600
caagcaataa tcaataagga aattgccaaa tttcttgata ggagaaatat tttgttactt 660
gaaaaaaacc ttttttcctt tcttaatatt tctgagattg aaaaattatt tgaaattatg 720
aataatttca aaaaaagtca aattgaaaag tataaaagtt tgactttcga taaaaaagat 780
gaaaaaaatt atacaaatac aaaattattt agtcaattaa tccgtaccga aattatcatt 840
ttggatattc aaggtttaaa agaaattgcc caaaatcgta aaaaaactta tcaagaaaaa 900
gtaaattttc aaacaaaatt tctccaattt aaaaataaat attcatataa taaaaaaaga 960
agtagtccgc aagccgaaaa tctagaaaaa ctcaatgaat taaaagaaaa actggcccaa 1020
aaagaagcaa tttatgaaga agaaaaagac ctttttatta gaaaatatac ctcttggaaa 1080
acaaaaccag agcaaaaaaa t 1101
<210> 46
<211> 367
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD922
<400> 46
Thr Asp Gln Ile Leu Ile Phe His Leu Ala Lys Thr Leu Asp Gln Lys
1 5 10 15
Tyr Leu Glu Ile Asp Leu Glu Met Leu Glu Lys Gly Asn Phe Glu Phe
20 25 30
Gln Asp Phe Ile Asn Phe Trp Gln Ser Arg Ile Glu Lys Ile Glu Glu
35 40 45
Asn Leu Ala Gln Ile Ser Thr Asp Lys Ile Thr Glu Ala Lys Ile Asn
50 55 60
Glu Phe Phe Asn Ser Tyr Leu Leu Tyr Phe Glu Lys Leu Gln Lys Leu
65 70 75 80
Phe Ser Ser Ser Tyr Asn Leu Gly Tyr Glu Asn Val Ala Lys Leu Tyr
85 90 95
Asp Tyr Phe Tyr Glu Val Gln Lys Ile Tyr Arg Gln Lys Gln Gln Ala
100 105 110
Lys Val Glu Phe Asp Tyr Arg Ser Ala Lys Lys Asp Tyr Glu Asp Gln
115 120 125
Leu Lys Lys Ile Lys Gln Glu Lys Ala Phe Phe Ile Lys Thr Leu Asn
130 135 140
Val Lys Ala Leu Asn Leu Lys Lys Glu Ala Gln Leu Glu Ile Asp Lys
145 150 155 160
Phe Thr Ala Gln Asn Asn Leu Leu Thr Ser Tyr Ile Asp Glu Phe Asn
165 170 175
Tyr Glu Tyr Lys Ile Ala Asn Asn Lys Ala Leu Val Thr Thr Asp Leu
180 185 190
Lys Asn Tyr Ser Phe Phe Lys Lys Gln Ala Ile Ile Asn Lys Glu Ile
195 200 205
Ala Lys Phe Leu Asp Arg Arg Asn Ile Leu Leu Leu Glu Lys Asn Leu
210 215 220
Phe Ser Phe Leu Asn Ile Ser Glu Ile Glu Lys Leu Phe Glu Ile Met
225 230 235 240
Asn Asn Phe Lys Lys Ser Gln Ile Glu Lys Tyr Lys Ser Leu Thr Phe
245 250 255
Asp Lys Lys Asp Glu Lys Asn Tyr Thr Asn Thr Lys Leu Phe Ser Gln
260 265 270
Leu Ile Arg Thr Glu Ile Ile Ile Leu Asp Ile Gln Gly Leu Lys Glu
275 280 285
Ile Ala Gln Asn Arg Lys Lys Thr Tyr Gln Glu Lys Val Asn Phe Gln
290 295 300
Thr Lys Phe Leu Gln Phe Lys Asn Lys Tyr Ser Tyr Asn Lys Lys Arg
305 310 315 320
Ser Ser Pro Gln Ala Glu Asn Leu Glu Lys Leu Asn Glu Leu Lys Glu
325 330 335
Lys Leu Ala Gln Lys Glu Ala Ile Tyr Glu Glu Glu Lys Asp Leu Phe
340 345 350
Ile Arg Lys Tyr Thr Ser Trp Lys Thr Lys Pro Glu Gln Lys Asn
355 360 365
<210> 47
<211> 438
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clones pAD923 and pAD925
<400> 47
tataatttaa aaaaagaaac taatttgagg aaatttttaa tgtcaaaaaa atctaaaaat 60
tcaagcattg aatttgatgc tattgttgtc ggtggcggcc atgctgggat cgaagcagtt 120
tatgcattat taaaaaaaaa gttaaaagtt gttctaataa ctcttgataa gaaaaaatta 180
gcttcaatgc cttgtaatcc cgcaattggt gggccagcaa aaggaattat aactcgcgag 240
atcgatgccc ttggaggagt tcagggaaaa ttttcagatt tagcaatgat ccaaattaaa 300
tatttaaatg aatcaaaagg tcctgccgtt ttagcaatta gagcccaaat tgataaggaa 360
aaatattcaa aattaatatt aaaggatttg aaaaaacagg aaaatttatt aattatcgag 420
gatttggtta gtgaactc 438
<210> 48
<211> 146
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clones pAD923 and pAD925
<400> 48
Tyr Asn Leu Lys Lys Glu Thr Asn Leu Arg Lys Phe Leu Met Ser Lys
1 5 10 15
Lys Ser Lys Asn Ser Ser Ile Glu Phe Asp Ala Ile Val Val Gly Gly
20 25 30
Gly His Ala Gly Ile Glu Ala Val Tyr Ala Leu Leu Lys Lys Lys Leu
35 40 45
Lys Val Val Leu Ile Thr Leu Asp Lys Lys Lys Leu Ala Ser Met Pro
50 55 60
Cys Asn Pro Ala Ile Gly Gly Pro Ala Lys Gly Ile Ile Thr Arg Glu
65 70 75 80
Ile Asp Ala Leu Gly Gly Val Gln Gly Lys Phe Ser Asp Leu Ala Met
85 90 95
Ile Gln Ile Lys Tyr Leu Asn Glu Ser Lys Gly Pro Ala Val Leu Ala
100 105 110
Ile Arg Ala Gln Ile Asp Lys Glu Lys Tyr Ser Lys Leu Ile Leu Lys
115 120 125
Asp Leu Lys Lys Gln Glu Asn Leu Leu Ile Ile Glu Asp Leu Val Ser
130 135 140
Glu Leu
145
<210> 49
<211> 1074
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD950
<400> 49
caaattgtac aatcagaacc agaaatttta aatcaaaaat tttttttatg taaaaaaata 60
ctacaggaac aaaaattaat tagtttttgc gaacaaaaat tagaaaaagc aaagaaaaat 120
aaccaatttg aactcgccaa cgaatatcac aaagcgctta ttgcactgaa aaaaactaaa 180
attgaacaac aaaatattga gcttaacaac ctaaaaaata ttgattttct ttattatagt 240
gaaattggcg agaataattt agtaattagt tttgcttttt atcgcaatgg tgttttttta 300
tctaataaaa attttattat tgatattata cttaattata cagaagtttt aattaatttt 360
ttaaataatt attataaaat taatatttat cccgatgagt tagtagttaa aaatttttgg 420
cctaaaaatg ctgaattttt agacccaaaa attaatatca aaattggaaa aagcttaaaa 480
tataagcata ttttaaacac tttagcaaaa aatcaccaag attttatcag ccataatttt 540
gaccaagaaa ttaagaaaaa aattaaaaat cagaaaattt tagaactagt taaaaccagt 600
ttaaaaattg aaaatgttga aaaaattatg gcaattgact gctcaaattt agagtcaaac 660
taccccacaa ctggaattat tttctatata aacggaatat atgagcgaaa ttacaataga 720
tttttcaatt ataggggaac aaaaaaaggt gatacaaatt atatgagaca gggttttgaa 780
aaatatatta aaaatccaaa atttctaaaa cctgatttga ttttagtaga tggaggaatt 840
caacaaatta atttaattat agaaatttta agaaaaaatc actttgaaat tccgattttt 900
ggaatggtaa aaaataaaag gcataaaact gaaaaaatta ttgacttaaa tggtaaaaaa 960
attaacctag ctcaagaagt tcttaatttc tttgctttaa ttcaagaaaa tgtcgattta 1020
tttgttaagg aaaaaatgaa gaaaaaacaa ataaaaagtt tattttctaa ggaa 1074
<210> 50
<211> 358
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequenc:Deduced protein sequence from C
lone pAD950
<400> 50
Gln Ile Val Gln Ser Glu Pro Glu Ile Leu Asn Gln Lys Phe Phe Leu
1 5 10 15
Cys Lys Lys Ile Leu Gln Glu Gln Lys Leu Ile Ser Phe Cys Glu Gln
20 25 30
Lys Leu Glu Lys Ala Lys Lys Asn Asn Gln Phe Glu Leu Ala Asn Glu
35 40 45
Tyr His Lys Ala Leu Ile Ala Leu Lys Lys Thr Lys Ile Glu Gln Gln
50 55 60
Asn Ile Glu Leu Asn Asn Leu Lys Asn Ile Asp Phe Leu Tyr Tyr Ser
65 70 75 80
Glu Ile Gly Glu Asn Asn Leu Val Ile Ser Phe Ala Phe Tyr Arg Asn
85 90 95
Gly Val Phe Leu Ser Asn Lys Asn Phe Ile Ile Asp Ile Ile Leu Asn
100 105 110
Tyr Thr Glu Val Leu Ile Asn Phe Leu Asn Asn Tyr Tyr Lys Ile Asn
115 120 125
Ile Tyr Pro Asp Glu Leu Val Val Lys Asn Phe Trp Pro Lys Asn Ala
130 135 140
Glu Phe Leu Asp Pro Lys Ile Asn Ile Lys Ile Gly Lys Ser Leu Lys
145 150 155 160
Tyr Lys His Ile Leu Asn Thr Leu Ala Lys Asn His Gln Asp Phe Ile
165 170 175
Ser His Asn Phe Asp Gln Glu Ile Lys Lys Lys Ile Lys Asn Gln Lys
180 185 190
Ile Leu Glu Leu Val Lys Thr Ser Leu Lys Ile Glu Asn Val Glu Lys
195 200 205
Ile Met Ala Ile Asp Cys Ser Asn Leu Glu Ser Asn Tyr Pro Thr Thr
210 215 220
Gly Ile Ile Phe Tyr Ile Asn Gly Ile Tyr Glu Arg Asn Tyr Asn Arg
225 230 235 240
Phe Phe Asn Tyr Arg Gly Thr Lys Lys Gly Asp Thr Asn Tyr Met Arg
245 250 255
Gln Gly Phe Glu Lys Tyr Ile Lys Asn Pro Lys Phe Leu Lys Pro Asp
260 265 270
Leu Ile Leu Val Asp Gly Gly Ile Gln Gln Ile Asn Leu Ile Ile Glu
275 280 285
Ile Leu Arg Lys Asn His Phe Glu Ile Pro Ile Phe Gly Met Val Lys
290 295 300
Asn Lys Arg His Lys Thr Glu Lys Ile Ile Asp Leu Asn Gly Lys Lys
305 310 315 320
Ile Asn Leu Ala Gln Glu Val Leu Asn Phe Phe Ala Leu Ile Gln Glu
325 330 335
Asn Val Asp Leu Phe Val Lys Glu Lys Met Lys Lys Lys Gln Ile Lys
340 345 350
Ser Leu Phe Ser Lys Glu
355
<210> 51
<211> 282
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD951
<400> 51
tcgaatataa ctgacaaaac aggaaaactt ttaaaaattt ctaacaataa aaatacttta 60
atttttaaag ttgttggagt ttttgatcct gaaaaagatg acgaaaatat tgctattttt 120
aacaataata ttgaaaaata ttctagtgaa ttacttccaa tagctgctgt ggtttatttt 180
gatcatgata atttatataa taatattaat gaatttttaa ataaatatag caaaccgggc 240
gttagtcgtt attactcgac aaatggcggc cggatcaaat tc 282
<210> 52
<211> 94
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD951
<400> 52
Ser Asn Ile Thr Asp Lys Thr Gly Lys Leu Leu Lys Ile Ser Asn Asn
1 5 10 15
Lys Asn Thr Leu Ile Phe Lys Val Val Gly Val Phe Asp Pro Glu Lys
20 25 30
Asp Asp Glu Asn Ile Ala Ile Phe Asn Asn Asn Ile Glu Lys Tyr Ser
35 40 45
Ser Glu Leu Leu Pro Ile Ala Ala Val Val Tyr Phe Asp His Asp Asn
50 55 60
Leu Tyr Asn Asn Ile Asn Glu Phe Leu Asn Lys Tyr Ser Lys Pro Gly
65 70 75 80
Val Ser Arg Tyr Tyr Ser Thr Asn Gly Gly Arg Ile Lys Phe
85 90
<210> 53
<211> 438
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD977
<400> 53
attttaatta ataattcaat tgaatataag gaattagacc caaaccagtt aagaaaacat 60
attgcactaa caacaaatga aaacataatt ttcgaagaca ctttggcaaa caacataact 120
ttatgagata aaaatcccga tttagatttg ctaaattctt taataaaaaa gtataaaatt 180
gataattttt caaaaccaga aactgaaatt agctcaaaaa atttatctga gggcgaaaaa 240
caaaaagttg cattggccag attagagtac aaaaatttag atatttgatg tttagatgaa 300
gctcttgata acattttcaa ggaagatgct tttgaaattt acagtgattt actttcaaaa 360
ccgaataaaa caatttttat cgcaagtcac cacattcctg aaaaaataaa accgatgttt 420
gaccaaataa ttgaaatt 438
<210> 54
<211> 146
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD977
<400> 54
Ile Leu Ile Asn Asn Ser Ile Glu Tyr Lys Glu Leu Asp Pro Asn Gln
1 5 10 15
Leu Arg Lys His Ile Ala Leu Thr Thr Asn Glu Asn Ile Ile Phe Glu
20 25 30
Asp Thr Leu Ala Asn Asn Ile Thr Leu Trp Asp Lys Asn Pro Asp Leu
35 40 45
Asp Leu Leu Asn Ser Leu Ile Lys Lys Tyr Lys Ile Asp Asn Phe Ser
50 55 60
Lys Pro Glu Thr Glu Ile Ser Ser Lys Asn Leu Ser Glu Gly Glu Lys
65 70 75 80
Gln Lys Val Ala Leu Ala Arg Leu Glu Tyr Lys Asn Leu Asp Ile Trp
85 90 95
Cys Leu Asp Glu Ala Leu Asp Asn Ile Phe Lys Glu Asp Ala Phe Glu
100 105 110
Ile Tyr Ser Asp Leu Leu Ser Lys Pro Asn Lys Thr Ile Phe Ile Ala
115 120 125
Ser His His Ile Pro Glu Lys Ile Lys Pro Met Phe Asp Gln Ile Ile
130 135 140
Glu Ile
145
<210> 55
<211> 400
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD983
<400> 55
tcaacgggct gccaaattga acctgacaaa ccgctggtaa aaaaatgggt tatgggtgtt 60
ttatttaatt atagctttta ttattcagga attctaagca tagttttagg atttttttct 120
tctgaaataa caattttctt tcttcaaaca gcaggggctg atattaatgt tccagtttga 180
ggccatctaa taattgggac agttttttgt atttttttca ctagccttaa ttatatttca 240
ataaaaacat caggatgaat tgcgcttgca tcaacaattt taaaatttat tcctttagta 300
tttgcagttt ttgcaggaat tctatttcca aaaacttata atgccggcgg ttctaatgcc 360
tttgttcaaa cagctcaaat agttttaatt ttgcaaaatt 400
<210> 56
<211> 133
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD983
<400> 56
Ser Thr Gly Cys Gln Ile Glu Pro Asp Lys Pro Leu Val Lys Lys Trp
1 5 10 15
Val Met Gly Val Leu Phe Asn Tyr Ser Phe Tyr Tyr Ser Gly Ile Leu
20 25 30
Ser Ile Val Leu Gly Phe Phe Ser Ser Glu Ile Thr Ile Phe Phe Leu
35 40 45
Gln Thr Ala Gly Ala Asp Ile Asn Val Pro Val Trp Gly His Leu Ile
50 55 60
Ile Gly Thr Val Phe Cys Ile Phe Phe Thr Ser Leu Asn Tyr Ile Ser
65 70 75 80
Ile Lys Thr Ser Gly Trp Ile Ala Leu Ala Ser Thr Ile Leu Lys Phe
85 90 95
Ile Pro Leu Val Phe Ala Val Phe Ala Gly Ile Leu Phe Pro Lys Thr
100 105 110
Tyr Asn Ala Gly Gly Ser Asn Ala Phe Val Gln Thr Ala Gln Ile Val
115 120 125
Leu Ile Leu Gln Asn
130
<210> 57
<211> 522
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD984
<400> 57
ttaaaaagtg aaaaccaaaa agaaacagca aatttaaata ctacttttac tcaaacaatt 60
agtaaaaaag atatcgaaat aaccaattta agaaatgaaa ttggcaaatt tcttgatgaa 120
aaagataaaa tgcgaagtga cattcttgca aatgatgatg agataaaggc gatgaggagt 180
gaaatttctc aactaaaaga agcaaatgcc aacctacaaa atgtcaagtt agaagaaatt 240
tcaaatttaa aactagaaca taaggacgaa attaatgaaa aagaccgtaa aattagttat 300
ttagagaata aatttaacga cttggaagaa gaaaaaaata attcaattca aaatgctgta 360
agtcaaaaaa cacgagaaat aaaggaaaaa attgaaaaag agctagaaat taaatgggga 420
agaaaaaata aaacaggaaa aatcagattt aagaggaaaa ttttaaggag caaattaata 480
aaccaggaga aaaaattcaa gattagaaga agaattaaat ta 522
<210> 58
<211> 174
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD984
<400> 58
Leu Lys Ser Glu Asn Gln Lys Glu Thr Ala Asn Leu Asn Thr Thr Phe
1 5 10 15
Thr Gln Thr Ile Ser Lys Lys Asp Ile Glu Ile Thr Asn Leu Arg Asn
20 25 30
Glu Ile Gly Lys Phe Leu Asp Glu Lys Asp Lys Met Arg Ser Asp Ile
35 40 45
Leu Ala Asn Asp Asp Glu Ile Lys Ala Met Arg Ser Glu Ile Ser Gln
50 55 60
Leu Lys Glu Ala Asn Ala Asn Leu Gln Asn Val Lys Leu Glu Glu Ile
65 70 75 80
Ser Asn Leu Lys Leu Glu His Lys Asp Glu Ile Asn Glu Lys Asp Arg
85 90 95
Lys Ile Ser Tyr Leu Glu Asn Lys Phe Asn Asp Leu Glu Glu Glu Lys
100 105 110
Asn Asn Ser Ile Gln Asn Ala Val Ser Gln Lys Thr Arg Glu Ile Lys
115 120 125
Glu Lys Ile Glu Lys Glu Leu Glu Ile Lys Trp Gly Arg Lys Asn Lys
130 135 140
Thr Gly Lys Ile Arg Phe Lys Arg Lys Ile Leu Arg Ser Lys Leu Ile
145 150 155 160
Asn Gln Glu Lys Lys Phe Lys Ile Arg Arg Arg Ile Lys Leu
165 170
<210> 59
<211> 633
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD994
<400> 59
attaaacact tttttaaaag atttgaaatg tataaacgat tagttcagga attctttcct 60
aaattagatt ttgaaaattt agaaaaatac gtaaatttaa ttgaatttag taataaaaac 120
tttaatttaa ccgctttttc tggtgatatt ctttgaaaag agggaatttt tgagtcaatt 180
tttacaatga atttcattgt tggtttagta aataataaag aaaataaaaa attaaaaatt 240
ttggatattg gggctggatc aggttttcct tcaattcctt ttttgattac aaacccagaa 300
attgagctaa caatttctga gtcaatgcaa aaaagatgcc agtttttaaa ggatgtttct 360
gaaaaattag atttgaaatt caatttaatt tgcaaaccag ttcaagaaat taatccacaa 420
aaatttgata taataactgc cagagcagtg gcaaatttgg aaaagcttga gaaaattaca 480
aaaaaaattc attttccaaa aacgctttta gcttttatta aagggcccaa agtttttaat 540
gaagttcaaa attgtaaaaa ttgtaattat aaaatcatta aagttaataa taatataaat 600
aaaaaaattt ttatcgcatt taaacaagtt tct 633
<210> 60
<211> 211
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD994
<400> 60
Ile Lys His Phe Phe Lys Arg Phe Glu Met Tyr Lys Arg Leu Val Gln
1 5 10 15
Glu Phe Phe Pro Lys Leu Asp Phe Glu Asn Leu Glu Lys Tyr Val Asn
20 25 30
Leu Ile Glu Phe Ser Asn Lys Asn Phe Asn Leu Thr Ala Phe Ser Gly
35 40 45
Asp Ile Leu Trp Lys Glu Gly Ile Phe Glu Ser Ile Phe Thr Met Asn
50 55 60
Phe Ile Val Gly Leu Val Asn Asn Lys Glu Asn Lys Lys Leu Lys Ile
65 70 75 80
Leu Asp Ile Gly Ala Gly Ser Gly Phe Pro Ser Ile Pro Phe Leu Ile
85 90 95
Thr Asn Pro Glu Ile Glu Leu Thr Ile Ser Glu Ser Met Gln Lys Arg
100 105 110
Cys Gln Phe Leu Lys Asp Val Ser Glu Lys Leu Asp Leu Lys Phe Asn
115 120 125
Leu Ile Cys Lys Pro Val Gln Glu Ile Asn Pro Gln Lys Phe Asp Ile
130 135 140
Ile Thr Ala Arg Ala Val Ala Asn Leu Glu Lys Leu Glu Lys Ile Thr
145 150 155 160
Lys Lys Ile His Phe Pro Lys Thr Leu Leu Ala Phe Ile Lys Gly Pro
165 170 175
Lys Val Phe Asn Glu Val Gln Asn Cys Lys Asn Cys Asn Tyr Lys Ile
180 185 190
Ile Lys Val Asn Asn Asn Ile Asn Lys Lys Ile Phe Ile Ala Phe Lys
195 200 205
Gln Val Ser
210
<210> 61
<211> 537
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD1005
<400> 61
atgaaaaaat tattagttat tttgcttgat aaattccagg atattgaact tacaactttt 60
atttccctga ttaaaaaagc agaaattttt acagatattg aattttttaa ccctaaaaat 120
aataaattag taataggtca attcggagtt gtatcaattc aagcacataa tcactggaaa 180
tcagatgact ttgatgctgt ttttattccg gggggttttg cggcccaatt attccgcaag 240
gattcaaaat caattcaact tgtgagcgag ttttttgcgc aaaacaaaca tatttttgcc 300
atttgtgatg caccaaatgc aatttttgaa ctaaaattag cagaaaatta tcaatttagt 360
tcatatccaa accaacataa ttccaaaatt agactaagac aagattcgtt agtaactatt 420
gaccgcaatt atatttcggc aagaaatgca gcaagttcgg cagattttgc tttcgttgta 480
attgaaaagc tgggatcaaa agagttagct caaaaaatta gaaatggatt ttatctt 537
<210> 62
<211> 179
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD1005
<400> 62
Met Lys Lys Leu Leu Val Ile Leu Leu Asp Lys Phe Gln Asp Ile Glu
1 5 10 15
Leu Thr Thr Phe Ile Ser Leu Ile Lys Lys Ala Glu Ile Phe Thr Asp
20 25 30
Ile Glu Phe Phe Asn Pro Lys Asn Asn Lys Leu Val Ile Gly Gln Phe
35 40 45
Gly Val Val Ser Ile Gln Ala His Asn His Trp Lys Ser Asp Asp Phe
50 55 60
Asp Ala Val Phe Ile Pro Gly Gly Phe Ala Ala Gln Leu Phe Arg Lys
65 70 75 80
Asp Ser Lys Ser Ile Gln Leu Val Ser Glu Phe Phe Ala Gln Asn Lys
85 90 95
His Ile Phe Ala Ile Cys Asp Ala Pro Asn Ala Ile Phe Glu Leu Lys
100 105 110
Leu Ala Glu Asn Tyr Gln Phe Ser Ser Tyr Pro Asn Gln His Asn Ser
115 120 125
Lys Ile Arg Leu Arg Gln Asp Ser Leu Val Thr Ile Asp Arg Asn Tyr
130 135 140
Ile Ser Ala Arg Asn Ala Ala Ser Ser Ala Asp Phe Ala Phe Val Val
145 150 155 160
Ile Glu Lys Leu Gly Ser Lys Glu Leu Ala Gln Lys Ile Arg Asn Gly
165 170 175
Phe Tyr Leu
<210> 63
<211> 486
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD1016
<400> 63
ttaatcgttt ttgcttatat gatgttggtt gtaatgaatt gaggttttgc ctctgccgga 60
cttaacggta aagcgggaat aagtggttat ttaggtcact tttttccaaa tgctaatgaa 120
gccccaggaa ccgttgtaaa tcaagcagtt aactggggta tcacaattgg tcgtggaatt 180
ggatcagttc ttgttggttg attaattgtg aaaatttcgc ataaatatac agtaattttg 240
tctttatttt ttatgctttt tggaattatt gccccttatt caccaactta tgccgggttt 300
ataattctta gaacaatttt tgcaattggc ggaacaatgc agattatttt aattcaacca 360
gttgtctcaa attatttaaa tcaaaggcaa aaagctgtta tttcacaagt tttccccttt 420
tttttatcca attggaacaa taattacgct tattcctttt gcaggaatta tttggtcaag 480
agctca 486
<210> 64
<211> 162
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD1016
<400> 64
Leu Ile Val Phe Ala Tyr Met Met Leu Val Val Met Asn Trp Gly Phe
1 5 10 15
Ala Ser Ala Gly Leu Asn Gly Lys Ala Gly Ile Ser Gly Tyr Leu Gly
20 25 30
His Phe Phe Pro Asn Ala Asn Glu Ala Pro Gly Thr Val Val Asn Gln
35 40 45
Ala Val Asn Trp Gly Ile Thr Ile Gly Arg Gly Ile Gly Ser Val Leu
50 55 60
Val Gly Trp Leu Ile Val Lys Ile Ser His Lys Tyr Thr Val Ile Leu
65 70 75 80
Ser Leu Phe Phe Met Leu Phe Gly Ile Ile Ala Pro Tyr Ser Pro Thr
85 90 95
Tyr Ala Gly Phe Ile Ile Leu Arg Thr Ile Phe Ala Ile Gly Gly Thr
100 105 110
Met Gln Ile Ile Leu Ile Gln Pro Val Val Ser Asn Tyr Leu Asn Gln
115 120 125
Arg Gln Lys Ala Val Ile Ser Gln Val Phe Pro Phe Phe Leu Ser Asn
130 135 140
Trp Asn Asn Asn Tyr Ala Tyr Ser Phe Cys Arg Asn Tyr Leu Val Lys
145 150 155 160
Ser Ser
<210> 65
<211> 456
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD1020
<400> 65
tctgatcgtt ttccagttac aagtttagaa aaattatttc aatttgtcgc taattcagcg 60
cctatttttg aaaaattcaa aaaagcaaaa gaaaaatttt atcaagcaaa atttgggact 120
aagatgaata gttgagaccg tttagttcca ttagttgaga caaaaaataa ttattctgtt 180
gaagatgcac aaaaaatagt gcttggggca atcaaaccat taggtcaaga atataaagat 240
gttgtagaaa aagcatttag ccaaagatga attgactatc attatgttga ttcaaaaaga 300
tctggtgctt attcaattgg gggttcatat gggcttgaaa aaaaatatat tttaatgaat 360
tatgacttta ctataaacgc agttcatact ttagcacatg aattaggtca ttcgctccat 420
tcttattatt ctgataaaaa ccagaattat cataat 456
<210> 66
<211> 152
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD1020
<400> 66
Ser Asp Arg Phe Pro Val Thr Ser Leu Glu Lys Leu Phe Gln Phe Val
1 5 10 15
Ala Asn Ser Ala Pro Ile Phe Glu Lys Phe Lys Lys Ala Lys Glu Lys
20 25 30
Phe Tyr Gln Ala Lys Phe Gly Thr Lys Met Asn Ser Trp Asp Arg Leu
35 40 45
Val Pro Leu Val Glu Thr Lys Asn Asn Tyr Ser Val Glu Asp Ala Gln
50 55 60
Lys Ile Val Leu Gly Ala Ile Lys Pro Leu Gly Gln Glu Tyr Lys Asp
65 70 75 80
Val Val Glu Lys Ala Phe Ser Gln Arg Trp Ile Asp Tyr His Tyr Val
85 90 95
Asp Ser Lys Arg Ser Gly Ala Tyr Ser Ile Gly Gly Ser Tyr Gly Leu
100 105 110
Glu Lys Lys Tyr Ile Leu Met Asn Tyr Asp Phe Thr Ile Asn Ala Val
115 120 125
His Thr Leu Ala His Glu Leu Gly His Ser Leu His Ser Tyr Tyr Ser
130 135 140
Asp Lys Asn Gln Asn Tyr His Asn
145 150
<210> 67
<211> 576
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD1027
<400> 67
gaattaatta gggaaaattt atcacttgca aaatcatttt atgttgataa aaataataat 60
ccttggatat caacaacaaa aaattttgaa aacttatttg attatgtaca aagcgagcat 120
ctaattaata ctaataaaat aaaaaattat atcacaaaca taaattttaa aatcaaaaaa 180
aatagtgaaa tacctgcttt agaacttaat aatttgctaa aagatgataa aattcggctt 240
gaaataaatg ttgatatctc aaagtgagtc caacaaaaac taattaaaat tttaagtttt 300
aagtttgatt gggacctaaa accagacctg aatcagtatg cccggatttt tgcacaaaat 360
ctacccgagc caaaatctga ggtattctta ctaagaaaag atgaaaattc agcagcgtga 420
actagtaaaa aactagtaaa tataataaat aaaattaagg gatttaacaa tggattagac 480
ccagaaaatc ctgatttaag gttagttagc caactttatt tacttgattt tggcaaaatt 540
ggtgatgaaa atgctataga aaattttaaa gggatt 576
<210> 68
<211> 192
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD1027
<400> 68
Glu Leu Ile Arg Glu Asn Leu Ser Leu Ala Lys Ser Phe Tyr Val Asp
1 5 10 15
Lys Asn Asn Asn Pro Trp Ile Ser Thr Thr Lys Asn Phe Glu Asn Leu
20 25 30
Phe Asp Tyr Val Gln Ser Glu His Leu Ile Asn Thr Asn Lys Ile Lys
35 40 45
Asn Tyr Ile Thr Asn Ile Asn Phe Lys Ile Lys Lys Asn Ser Glu Ile
50 55 60
Pro Ala Leu Glu Leu Asn Asn Leu Leu Lys Asp Asp Lys Ile Arg Leu
65 70 75 80
Glu Ile Asn Val Asp Ile Ser Lys Trp Val Gln Gln Lys Leu Ile Lys
85 90 95
Ile Leu Ser Phe Lys Phe Asp Trp Asp Leu Lys Pro Asp Leu Asn Gln
100 105 110
Tyr Ala Arg Ile Phe Ala Gln Asn Leu Pro Glu Pro Lys Ser Glu Val
115 120 125
Phe Leu Leu Arg Lys Asp Glu Asn Ser Ala Ala Trp Thr Ser Lys Lys
130 135 140
Leu Val Asn Ile Ile Asn Lys Ile Lys Gly Phe Asn Asn Gly Leu Asp
145 150 155 160
Pro Glu Asn Pro Asp Leu Arg Leu Val Ser Gln Leu Tyr Leu Leu Asp
165 170 175
Phe Gly Lys Ile Gly Asp Glu Asn Ala Ile Glu Asn Phe Lys Gly Ile
180 185 190
<210> 69
<211> 351
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD1037
<400> 69
catatgttaa ttgaagtttt aataattcac taccgtcaag ttcagtatgg ccaaagtatt 60
aaaaaatcag taatttataa cttaataaca accctgattt tagtgccgat tattacagtt 120
ggcgcctttt tgaaccgttt ttttattaaa acaggctgac taataccatt ttttaatgtt 180
tctggcgggg caattttaag ttttgttgtc ataattgagt tagttccaga atttatccat 240
ttaagaaata acccttcttt tcagtgacat ttttctcttt ttttgtttgc tttaggaatt 300
attttagcct taattatttt aatttacatg aacattaagc gccgtagatc c 351
<210> 70
<211> 117
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD1037
<400> 70
His Met Leu Ile Glu Val Leu Ile Ile His Tyr Arg Gln Val Gln Tyr
1 5 10 15
Gly Gln Ser Ile Lys Lys Ser Val Ile Tyr Asn Leu Ile Thr Thr Leu
20 25 30
Ile Leu Val Pro Ile Ile Thr Val Gly Ala Phe Leu Asn Arg Phe Phe
35 40 45
Ile Lys Thr Gly Trp Leu Ile Pro Phe Phe Asn Val Ser Gly Gly Ala
50 55 60
Ile Leu Ser Phe Val Val Ile Ile Glu Leu Val Pro Glu Phe Ile His
65 70 75 80
Leu Arg Asn Asn Pro Ser Phe Gln Trp His Phe Ser Leu Phe Leu Phe
85 90 95
Ala Leu Gly Ile Ile Leu Ala Leu Ile Ile Leu Ile Tyr Met Asn Ile
100 105 110
Lys Arg Arg Arg Ser
115
<210> 71
<211> 1776
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD1038
<400> 71
gaattcgaaa aacgaattaa ggcaattttg caagaaattg agcaaaattc cgatcaagtt 60
attattttta ttgatgaaat tcaccttcta attggaacag gatcttctgg gactgattca 120
atggattttg ccaatatcct aaaaccaatt atggctcgcg gacagattaa attaatcggg 180
gctaccacaa attccgaata tcgcttatat atcgaaaaag atggcgccct tgaaagaaga 240
atgcaaaaag tagaaatttt agagccttca gttattgata caattaatat tttacgggga 300
attaaggaaa ggctagaaaa tttccatcaa gtaaaaatta aggattctgc tcttgttttt 360
gctacaaaag cggcaaatcg ttacattttt gaccgctttc tacctgataa agctatcgat 420
ttagtcgatg aagctgctgc ttctttaaaa gttgaaatca actaccaacc agaaaaactt 480
gaaaaagcaa agcgcgagct aatttattta aaaatggaag aaattaactc gcaaaaacaa 540
gataattcag aattaaaatc caaaattgaa aatcttgaaa atgaagtaaa aaaattacaa 600
gatcaatggg atcaatcaaa aaaatcagcc tctgaaatcg ctagcttatc ccaggaactt 660
gaaaaactaa aatatcaaca aaattactta atggaacaag gagactacca aaaagccgcc 720
gagattaaat acggaaaaat tcccaaaata agtaaaaaat taggcgaaat taaagcaaga 780
aggcaggaaa tttccaatgt tctagacgaa agtcagatcg caaaggttgt ctctaattga 840
acaaaaattc cgattgaaaa acttttagaa tcagaaattc aaaaatattt gaatttagaa 900
aaaaatttag caaaatcgct taagggtcaa aatcaggcaa ttaaggctgt ttcagatgcg 960
attttgcggt ttaaagctaa aattaatgat gaatcccgcc caatttcatc atttttcttt 1020
atgggaccaa ctggggtggg aaaaactgaa cttgctagag ctttagctct taatttattt 1080
aataataaaa accaaataat ccgtcttgat atgtcagaat atatggaaaa acatagtgtt 1140
tcaaagctaa ttggggctcc tccgggttat attggttttg aacaaggtgg taatctaaca 1200
aataaagtaa gactaaatcc ttattcgatt attttgcttg atgaaattga aaaagctcat 1260
ccggaagtaa tcaacatttt tttacaaatt cttgataatg gtgaaattgt tgatagtaag 1320
tcacaaaaag taaattttcg caatacaatt ataattatga cctcaaatat cggtgctaat 1380
aaaattcttg agggtaaaaa gatgaatgaa attgaggcaa aaaaggaact tttaagatat 1440
ttaaagccag aatttctcaa ccgaattgat gaaattatcg tatttaatcc tttaaattat 1500
gatataattt ttgaaattat tgaacttgaa ctaaaggatt tgcaaaatcg tctaaaggaa 1560
aataattttg agattgaatt tgaaaaatca gtcaaaaatt gaattttaga gtttggatat 1620
gataaaaatt ttggtgccag gccaattaag cgctttatta agaaagaaat tgaaaatttt 1680
gttgccaaaa aaatagtggc cgaagaaatt ttaaaagata aaaaatacaa tttatctttt 1740
aaaaatgata aattgcatct taatgaaagc gaaaat 1776
<210> 72
<211> 592
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD1038
<400> 72
Glu Phe Glu Lys Arg Ile Lys Ala Ile Leu Gln Glu Ile Glu Gln Asn
1 5 10 15
Ser Asp Gln Val Ile Ile Phe Ile Asp Glu Ile His Leu Leu Ile Gly
20 25 30
Thr Gly Ser Ser Gly Thr Asp Ser Met Asp Phe Ala Asn Ile Leu Lys
35 40 45
Pro Ile Met Ala Arg Gly Gln Ile Lys Leu Ile Gly Ala Thr Thr Asn
50 55 60
Ser Glu Tyr Arg Leu Tyr Ile Glu Lys Asp Gly Ala Leu Glu Arg Arg
65 70 75 80
Met Gln Lys Val Glu Ile Leu Glu Pro Ser Val Ile Asp Thr Ile Asn
85 90 95
Ile Leu Arg Gly Ile Lys Glu Arg Leu Glu Asn Phe His Gln Val Lys
100 105 110
Ile Lys Asp Ser Ala Leu Val Phe Ala Thr Lys Ala Ala Asn Arg Tyr
115 120 125
Ile Phe Asp Arg Phe Leu Pro Asp Lys Ala Ile Asp Leu Val Asp Glu
130 135 140
Ala Ala Ala Ser Leu Lys Val Glu Ile Asn Tyr Gln Pro Glu Lys Leu
145 150 155 160
Glu Lys Ala Lys Arg Glu Leu Ile Tyr Leu Lys Met Glu Glu Ile Asn
165 170 175
Ser Gln Lys Gln Asp Asn Ser Glu Leu Lys Ser Lys Ile Glu Asn Leu
180 185 190
Glu Asn Glu Val Lys Lys Leu Gln Asp Gln Trp Asp Gln Ser Lys Lys
195 200 205
Ser Ala Ser Glu Ile Ala Ser Leu Ser Gln Glu Leu Glu Lys Leu Lys
210 215 220
Tyr Gln Gln Asn Tyr Leu Met Glu Gln Gly Asp Tyr Gln Lys Ala Ala
225 230 235 240
Glu Ile Lys Tyr Gly Lys Ile Pro Lys Ile Ser Lys Lys Leu Gly Glu
245 250 255
Ile Lys Ala Arg Arg Gln Glu Ile Ser Asn Val Leu Asp Glu Ser Gln
260 265 270
Ile Ala Lys Val Val Ser Asn Trp Thr Lys Ile Pro Ile Glu Lys Leu
275 280 285
Leu Glu Ser Glu Ile Gln Lys Tyr Leu Asn Leu Glu Lys Asn Leu Ala
290 295 300
Lys Ser Leu Lys Gly Gln Asn Gln Ala Ile Lys Ala Val Ser Asp Ala
305 310 315 320
Ile Leu Arg Phe Lys Ala Lys Ile Asn Asp Glu Ser Arg Pro Ile Ser
325 330 335
Ser Phe Phe Phe Met Gly Pro Thr Gly Val Gly Lys Thr Glu Leu Ala
340 345 350
Arg Ala Leu Ala Leu Asn Leu Phe Asn Asn Lys Asn Gln Ile Ile Arg
355 360 365
Leu Asp Met Ser Glu Tyr Met Glu Lys His Ser Val Ser Lys Leu Ile
370 375 380
Gly Ala Pro Pro Gly Tyr Ile Gly Phe Glu Gln Gly Gly Asn Leu Thr
385 390 395 400
Asn Lys Val Arg Leu Asn Pro Tyr Ser Ile Ile Leu Leu Asp Glu Ile
405 410 415
Glu Lys Ala His Pro Glu Val Ile Asn Ile Phe Leu Gln Ile Leu Asp
420 425 430
Asn Gly Glu Ile Val Asp Ser Lys Ser Gln Lys Val Asn Phe Arg Asn
435 440 445
Thr Ile Ile Ile Met Thr Ser Asn Ile Gly Ala Asn Lys Ile Leu Glu
450 455 460
Gly Lys Lys Met Asn Glu Ile Glu Ala Lys Lys Glu Leu Leu Arg Tyr
465 470 475 480
Leu Lys Pro Glu Phe Leu Asn Arg Ile Asp Glu Ile Ile Val Phe Asn
485 490 495
Pro Leu Asn Tyr Asp Ile Ile Phe Glu Ile Ile Glu Leu Glu Leu Lys
500 505 510
Asp Leu Gln Asn Arg Leu Lys Glu Asn Asn Phe Glu Ile Glu Phe Glu
515 520 525
Lys Ser Val Lys Asn Trp Ile Leu Glu Phe Gly Tyr Asp Lys Asn Phe
530 535 540
Gly Ala Arg Pro Ile Lys Arg Phe Ile Lys Lys Glu Ile Glu Asn Phe
545 550 555 560
Val Ala Lys Lys Ile Val Ala Glu Glu Ile Leu Lys Asp Lys Lys Tyr
565 570 575
Asn Leu Ser Phe Lys Asn Asp Lys Leu His Leu Asn Glu Ser Glu Asn
580 585 590
<210> 73
<211> 796
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD1040
<400> 73
atggtaaaat ctacaaaaca tttcaaattt atcctttgaa attgattata tttgattttt 60
acgatttttt ttaaaattta tctcattgtt gctccttatt ttatttttac ttttattcta 120
aatgaaaatt taactttttt ttgggtagcc acaacatctt ttttaggggt tagaattttt 180
aatatctttt tagattttat gaatcaagca tattttaaag ggtttttgat ctttcataag 240
atgaaacttg ccgaaaaaat aacaaatttt ttggaaaaaa cgacttacaa aaaatataac 300
gaaaattcaa gtgggtttta ctattcggaa attgaaaata caatagaaaa aagcgtttca 360
caattttatg caaatttatt gtcctttttg caaactcttt ccataatttt gatgacttta 420
ggtttatttt tttatataaa ctggatttta gcgttaatta ttgtcggtgt tataaccttt 480
tttgtaatta caacttcttt actatctaaa aaattaacca aacttcaatc cgcaaaattg 540
caagcaattt cggattttaa caattcttta agcacttatc ttttaacttt gccgcaatta 600
aaaaccttaa attctgatga taaattcgaa tttataatta ataaaagaaa caagaaaaat 660
tgaataacta gagaaaaata tggtatattt tccgacttaa tttcattttt taatgaatat 720
tccaataatt ttttctccgc aataatcaca attggaattg cattttggac actttattat 780
aaaaataata atagct 796
<210> 74
<211> 265
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD1040
<400> 74
Met Val Lys Ser Thr Lys His Phe Lys Phe Ile Leu Trp Asn Trp Leu
1 5 10 15
Tyr Leu Ile Phe Thr Ile Phe Phe Lys Ile Tyr Leu Ile Val Ala Pro
20 25 30
Tyr Phe Ile Phe Thr Phe Ile Leu Asn Glu Asn Leu Thr Phe Phe Trp
35 40 45
Val Ala Thr Thr Ser Phe Leu Gly Val Arg Ile Phe Asn Ile Phe Leu
50 55 60
Asp Phe Met Asn Gln Ala Tyr Phe Lys Gly Phe Leu Ile Phe His Lys
65 70 75 80
Met Lys Leu Ala Glu Lys Ile Thr Asn Phe Leu Glu Lys Thr Thr Tyr
85 90 95
Lys Lys Tyr Asn Glu Asn Ser Ser Gly Phe Tyr Tyr Ser Glu Ile Glu
100 105 110
Asn Thr Ile Glu Lys Ser Val Ser Gln Phe Tyr Ala Asn Leu Leu Ser
115 120 125
Phe Leu Gln Thr Leu Ser Ile Ile Leu Met Thr Leu Gly Leu Phe Phe
130 135 140
Tyr Ile Asn Trp Ile Leu Ala Leu Ile Ile Val Gly Val Ile Thr Phe
145 150 155 160
Phe Val Ile Thr Thr Ser Leu Leu Ser Lys Lys Leu Thr Lys Leu Gln
165 170 175
Ser Ala Lys Leu Gln Ala Ile Ser Asp Phe Asn Asn Ser Leu Ser Thr
180 185 190
Tyr Leu Leu Thr Leu Pro Gln Leu Lys Thr Leu Asn Ser Asp Asp Lys
195 200 205
Phe Glu Phe Ile Ile Asn Lys Arg Asn Lys Lys Asn Trp Ile Thr Arg
210 215 220
Glu Lys Tyr Gly Ile Phe Ser Asp Leu Ile Ser Phe Phe Asn Glu Tyr
225 230 235 240
Ser Asn Asn Phe Phe Ser Ala Ile Ile Thr Ile Gly Ile Ala Phe Trp
245 250 255
Thr Leu Tyr Tyr Lys Asn Asn Asn Ser
260 265
<210> 75
<211> 453
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD702
<400> 75
tcttatgaga aaaaatattt acctttgcta atagtccctg gaatttttgg cgctatttta 60
ttttttcttt ttattaaaac acttttagac tataaagcaa tcaaaaaatc tgttatttat 120
tttcgttccc agttgcaaaa taatgcaaat cgacttgaaa tgccaccaat gattccatga 180
cttgtaaaaa aagtgaatca aaaagaggta aatgctatct gacttagcgg ctttactttg 240
tttgcaacaa ttatgatggg cttaacttac tgagtgttat taaaatatta tccggagaaa 300
aatattcaaa attctgccga atatataact gcaatggcag taaatggcgc tttgtttata 360
gttatgctaa tttatgattt aatgcttcgt cggcgtttgg gaaatattga agcaattttt 420
ggtcccattt atcataaaag ttttgatata ggt 453
<210> 76
<211> 151
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD702
<400> 76
Ser Tyr Glu Lys Lys Tyr Leu Pro Leu Leu Ile Val Pro Gly Ile Phe
1 5 10 15
Gly Ala Ile Leu Phe Phe Leu Phe Ile Lys Thr Leu Leu Asp Tyr Lys
20 25 30
Ala Ile Lys Lys Ser Val Ile Tyr Phe Arg Ser Gln Leu Gln Asn Asn
35 40 45
Ala Asn Arg Leu Glu Met Pro Pro Met Ile Pro Trp Leu Val Lys Lys
50 55 60
Val Asn Gln Lys Glu Val Asn Ala Ile Trp Leu Ser Gly Phe Thr Leu
65 70 75 80
Phe Ala Thr Ile Met Met Gly Leu Thr Tyr Trp Val Leu Leu Lys Tyr
85 90 95
Tyr Pro Glu Lys Asn Ile Gln Asn Ser Ala Glu Tyr Ile Thr Ala Met
100 105 110
Ala Val Asn Gly Ala Leu Phe Ile Val Met Leu Ile Tyr Asp Leu Met
115 120 125
Leu Arg Arg Arg Leu Gly Asn Ile Glu Ala Ile Phe Gly Pro Ile Tyr
130 135 140
His Lys Ser Phe Asp Ile Gly
145 150
<210> 77
<211> 99
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD763
<400> 77
gatctttgtg ttatttttgt taataaaacc aagtttaaaa gtcatttccc ctggtttgtc 60
agtggtttta acatcataat aatagacaaa ataattctt 99
<210> 78
<211> 33
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
pAD763
<400> 78
Asp Leu Cys Val Ile Phe Val Asn Lys Thr Lys Phe Lys Ser His Phe
1 5 10 15
Pro Trp Phe Val Ser Gly Phe Asn Ile Ile Ile Ile Asp Lys Ile Ile
20 25 30
Leu
<210> 79
<211> 489
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD766
<400> 79
gatcaacaaa aaccacaacc aaaagaagaa aaagaagaaa aacaagaaaa agaagaaaaa 60
aaaccgccga tagttcaagg tcctagtcca aaaccacaaa agattgaaaa tatcggtctt 120
gttaatgatt tttataaata caagtttaac gataaaattc ataaatttga accgactgag 180
tattataaaa atacagcaaa tttttctcag ggtggccttt atagtgcaaa tttgctcgaa 240
ttagaaaagg aaataaagaa acaagatccg gataatccta aaatatttta tgttcaaaga 300
cgaattgata ttggtggttt tctaacaaaa ggcacacttt taccatttca acccgcaaat 360
cttgagaata atttatcaag cctttcgctt tttgatagat attcccaatt tctgaggagc 420
ggcagattcg ataacaatta ttatataatt ggatccgata aggttgagga atttgatagg 480
ttgaaaaga 489
<210> 80
<211> 163
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD766
<400> 80
Asp Gln Gln Lys Pro Gln Pro Lys Glu Glu Lys Glu Glu Lys Gln Glu
1 5 10 15
Lys Glu Glu Lys Lys Pro Pro Ile Val Gln Gly Pro Ser Pro Lys Pro
20 25 30
Gln Lys Ile Glu Asn Ile Gly Leu Val Asn Asp Phe Tyr Lys Tyr Lys
35 40 45
Phe Asn Asp Lys Ile His Lys Phe Glu Pro Thr Glu Tyr Tyr Lys Asn
50 55 60
Thr Ala Asn Phe Ser Gln Gly Gly Leu Tyr Ser Ala Asn Leu Leu Glu
65 70 75 80
Leu Glu Lys Glu Ile Lys Lys Gln Asp Pro Asp Asn Pro Lys Ile Phe
85 90 95
Tyr Val Gln Arg Arg Ile Asp Ile Gly Gly Phe Leu Thr Lys Gly Thr
100 105 110
Leu Leu Pro Phe Gln Pro Ala Asn Leu Glu Asn Asn Leu Ser Ser Leu
115 120 125
Ser Leu Phe Asp Arg Tyr Ser Gln Phe Leu Arg Ser Gly Arg Phe Asp
130 135 140
Asn Asn Tyr Tyr Ile Ile Gly Ser Asp Lys Val Glu Glu Phe Asp Arg
145 150 155 160
Leu Lys Arg
<210> 81
<211> 474
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD957
<400> 81
agctatttta gtattataag ccctttgttt ttggctgttt cttgcacaaa cattataatt 60
agcaaatctg aattatcaaa aatagaaagt aatattttta attttataat aaacgaaaat 120
gaaaaaaatt taactagatt taccgcaact ttagtaaaaa aaactaataa taacttgact 180
tttgtcagta cttttcattc gctaaattca ataaaaaaca atatacagca acaagttttt 240
gatatttttt tacaacaatt tagtgtgaaa aatttagaaa ctaaattaaa atcaaaaatt 300
agagttgaat atgaaaataa agaaaaagat atcatagttt tttcgctaga tataaaggaa 360
cccttattgt tgagaatttc ggattctatt gattttcagg ttctagagga ttttacaaac 420
acaaaaaata gcctatttag cttaaggttt ctcaccgatc ttaaacgaag attt 474
<210> 82
<211> 158
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
clone pAD957
<400> 82
Ser Tyr Phe Ser Ile Ile Ser Pro Leu Phe Leu Ala Val Ser Cys Thr
1 5 10 15
Asn Ile Ile Ile Ser Lys Ser Glu Leu Ser Lys Ile Glu Ser Asn Ile
20 25 30
Phe Asn Phe Ile Ile Asn Glu Asn Glu Lys Asn Leu Thr Arg Phe Thr
35 40 45
Ala Thr Leu Val Lys Lys Thr Asn Asn Asn Leu Thr Phe Val Ser Thr
50 55 60
Phe His Ser Leu Asn Ser Ile Lys Asn Asn Ile Gln Gln Gln Val Phe
65 70 75 80
Asp Ile Phe Leu Gln Gln Phe Ser Val Lys Asn Leu Glu Thr Lys Leu
85 90 95
Lys Ser Lys Ile Arg Val Glu Tyr Glu Asn Lys Glu Lys Asp Ile Ile
100 105 110
Val Phe Ser Leu Asp Ile Lys Glu Pro Leu Leu Leu Arg Ile Ser Asp
115 120 125
Ser Ile Asp Phe Gln Val Leu Glu Asp Phe Thr Asn Thr Lys Asn Ser
130 135 140
Leu Phe Ser Leu Arg Phe Leu Thr Asp Leu Lys Arg Arg Phe
145 150 155
<210> 83
<211> 123
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Clone pAD996
<400> 83
agctatctat taattatgat gccgcagggg gaacctatca cactactggt taaggtcatt 60
acgctagcgg ttatgcactc agatgaaaat gctgaaaggt acataaactc tgatgatccg 120
atc 123
<210> 84
<211> 41
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Deduced protein sequence from
pAD996
<400> 84
Ser Tyr Leu Leu Ile Met Met Pro Gln Gly Glu Pro Ile Thr Leu Leu
1 5 10 15
Val Lys Val Ile Thr Leu Ala Val Met His Ser Asp Glu Asn Ala Glu
20 25 30
Arg Tyr Ile Asn Ser Asp Asp Pro Ile
35 40
Claims (70)
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- 도 1a 내지 42 중의 어느 하나에 따른 서열, 또는 SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:77, SEQ ID NO:79, SEQ ID NO:81 또는 SEQ ID NO:83을 가진 마이코플라스마의 뉴클레오티드 서열.
- 삭제
- 제 49항에 따른 뉴클레오티드 서열을 포함하는 재조합 벡터.
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- 제 51항에 따른 재조합 벡터를 포함하는 숙주 세포.
- 도 1a 내지 42 중의 어느 하나에 따른 서열, 또는 SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO 62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO 74, SEQ ID NO: 76, SEQ ID NO:78, SEQ ID NO:80, SEQ ID NO:82 또는 SEQ ID NO:84을 가진 마이코플라스마의 아미노산 서열.
- 제 54항에 따른 아미노산 서열에 의해 암호화된 분리 및 정제된 폴리펩티드.
- 삭제
- 제 49항에 따른 뉴클레오티드 서열로부터 번역된 분리 및 정제된 폴리펩티드.
- 제 55항에 따른 폴리펩티드에 특이적인 항체.
- 삭제
- 제 57항에 따른 폴리펩티드에 특이적인 항체.
- 제 58항 또는 제 60항에 있어서,상기 항체가 모노클로날 항체인 것을 특징으로 하는 항체.
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AUPP7273 | 1998-11-20 | ||
| AUPP7273A AUPP727398A0 (en) | 1998-11-20 | 1998-11-20 | Methods of identifying antigen gene sequences |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20010081018A KR20010081018A (ko) | 2001-08-25 |
| KR100810699B1 true KR100810699B1 (ko) | 2008-03-07 |
Family
ID=3811482
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020017006157A KR100810699B1 (ko) | 1998-11-20 | 1999-11-19 | 항원 유전자 서열의 동정 방법 |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US6759516B2 (ko) |
| EP (1) | EP1140978A4 (ko) |
| JP (1) | JP2002535604A (ko) |
| KR (1) | KR100810699B1 (ko) |
| CN (1) | CN1331699A (ko) |
| AU (1) | AUPP727398A0 (ko) |
| BR (1) | BR9915066A (ko) |
| CA (1) | CA2351736A1 (ko) |
| HU (1) | HUP0104519A3 (ko) |
| MX (1) | MXPA01005011A (ko) |
| NZ (1) | NZ511623A (ko) |
| WO (1) | WO2000031115A1 (ko) |
| ZA (1) | ZA200103677B (ko) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20190104312A (ko) * | 2016-10-31 | 2019-09-09 | 유니베르시태트 취리히 | 단백질 스크리닝 및 검출 방법 |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ527679A (en) * | 2001-02-07 | 2005-07-29 | Invitrogen Corp | Nucleic acid Ter-(termination sequence) sites and Ter-binding proteins or RTPs in vitro and in vivo or combinations thereof |
| PT1546357E (pt) | 2002-06-28 | 2013-09-10 | Univ Iowa State Res Found Inc | Polipéptidos imunogénicos de mycoplasma hyopneumoniae |
| EP1812055A4 (en) * | 2004-11-11 | 2008-09-03 | Univ Queensland | CHLAMYDIEN-ANTIGENE AND ITS USES |
| CN101851661B (zh) * | 2010-05-10 | 2015-09-09 | 其昌達生物高科技(上海)有限公司 | 非诊断目的的在a-peg-b列阵下加快检测支原体时间的方法 |
| WO2015123728A1 (en) * | 2014-02-18 | 2015-08-27 | University Of Technology, Sydney | Mycoplasma surface proteins and uses thereof |
| BR102014014727B1 (pt) * | 2014-06-16 | 2018-04-03 | Ouro Fino Saúde Animal Ltda | COMPLEXO DE POLIPROTEÍNAS IMUNOGÊNICAS DE M. hyopneumoniae, GENE SINTÉTICO CODIFICANTE DO COMPLEXO DE POLIPROTEÍNAS IMUNOGÊNICAS DE M. hyopneumoniae, COMPOSIÇÃO ANTIGÊNICA, PROCESSO DE OBTENÇÃO DE UM COMPLEXO DE POLIPROTEÍNAS IMUNOGÊNICAS DE M. hyopneumoniae |
| CN112979769B (zh) * | 2021-03-08 | 2023-01-31 | 珠海丽禾医疗诊断产品有限公司 | 一种氨基酸序列、蛋白质及其制备方法和应用 |
| CN113185588A (zh) * | 2021-04-28 | 2021-07-30 | 华中农业大学 | 一种牛支原体MbovP701蛋白及其制备方法与应用 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0359919A2 (en) * | 1988-06-29 | 1990-03-28 | Ml Technology Ventures, L.P. | Recombinant mycoplasma hyopneumoniae antigen and uses therefor |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1993003157A1 (en) * | 1991-07-29 | 1993-02-18 | Dana Farber Cancer Institute | Plasmids for the rapid preparation of modified proteins |
| US5703057A (en) * | 1995-04-07 | 1997-12-30 | Board Of Regents The University Of Texas System | Expression library immunization |
-
1998
- 1998-11-20 AU AUPP7273A patent/AUPP727398A0/en not_active Abandoned
-
1999
- 1999-11-19 MX MXPA01005011A patent/MXPA01005011A/es not_active IP Right Cessation
- 1999-11-19 CN CN99814733A patent/CN1331699A/zh active Pending
- 1999-11-19 KR KR1020017006157A patent/KR100810699B1/ko not_active IP Right Cessation
- 1999-11-19 EP EP99957754A patent/EP1140978A4/en not_active Withdrawn
- 1999-11-19 HU HU0104519A patent/HUP0104519A3/hu unknown
- 1999-11-19 CA CA002351736A patent/CA2351736A1/en not_active Abandoned
- 1999-11-19 BR BR9915066-2A patent/BR9915066A/pt not_active Application Discontinuation
- 1999-11-19 WO PCT/AU1999/001035 patent/WO2000031115A1/en active IP Right Grant
- 1999-11-19 JP JP2000583942A patent/JP2002535604A/ja active Pending
- 1999-11-19 NZ NZ511623A patent/NZ511623A/xx unknown
-
2001
- 2001-05-07 ZA ZA200103677A patent/ZA200103677B/en unknown
- 2001-05-21 US US09/861,451 patent/US6759516B2/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0359919A2 (en) * | 1988-06-29 | 1990-03-28 | Ml Technology Ventures, L.P. | Recombinant mycoplasma hyopneumoniae antigen and uses therefor |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20190104312A (ko) * | 2016-10-31 | 2019-09-09 | 유니베르시태트 취리히 | 단백질 스크리닝 및 검출 방법 |
| KR102264642B1 (ko) | 2016-10-31 | 2021-06-15 | 유니베르시태트 취리히 | 단백질 스크리닝 및 검출 방법 |
Also Published As
| Publication number | Publication date |
|---|---|
| AUPP727398A0 (en) | 1998-12-17 |
| US6759516B2 (en) | 2004-07-06 |
| WO2000031115A1 (en) | 2000-06-02 |
| MXPA01005011A (es) | 2002-04-24 |
| NZ511623A (en) | 2003-04-29 |
| CA2351736A1 (en) | 2000-06-02 |
| CN1331699A (zh) | 2002-01-16 |
| JP2002535604A (ja) | 2002-10-22 |
| HUP0104519A3 (en) | 2004-10-28 |
| US20020068289A1 (en) | 2002-06-06 |
| HUP0104519A2 (hu) | 2002-03-28 |
| EP1140978A1 (en) | 2001-10-10 |
| EP1140978A4 (en) | 2006-03-01 |
| KR20010081018A (ko) | 2001-08-25 |
| BR9915066A (pt) | 2002-01-15 |
| ZA200103677B (en) | 2002-05-07 |
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