KR20220069045A - 안정성이 향상된 신규 히알루론산 가수분해 효소 변이체 및 이를 포함하는 약제학적 조성물 - Google Patents
안정성이 향상된 신규 히알루론산 가수분해 효소 변이체 및 이를 포함하는 약제학적 조성물 Download PDFInfo
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Abstract
본 발명은 히알루론산 가수분해 효소인 인간 히알루로니다제의 효소 활성과 열 안정성이 향상된 신규 PH20 변이체 또는 이의 절편에 관한 것으로, 서열번호 3의 아미노산 서열을 갖는 변이체에서 하나 이상의 아미노산 잔기의 치환과, 선택적으로 추가적인 N-말단 및/또는 C-말단의 아미노산 잔기가 결실된, 신규 PH20 변이체 또는 이의 절편에 대한 것이다.
Description
본 발명은 히알루론산 가수분해 효소인 인간 히알루로니다제의 효소 활성과 열 안정성을 향상시킨 신규 인간 PH20 변이체 또는 이의 절편에 관한 것으로, 구체적으로는 서열번호 3의 아미노산 서열을 가지는 히알루로니다제 변이체에 있어, 하나 이상의 아미노산 잔기의 치환, 결실 및/또는 삽입을 포함하고, 선택적으로 N-말단 및/또는 C-말단의 아미노산 잔기 일부가 결실된 PH20 변이체 또는 이의 절편, 이의 제조 방법 및 이를 포함하는 약제학적 조성물에 관한 것이다.
인간의 피부는 표피, 진피, 피하지방층으로 구성되어 있으며, 피부에는 6 종류의 글리코사미노글리칸(glycosaminoglycan)이 존재한다. 글리코사미노글리칸에는 히알루론산(hyaluronic acid), 콘드로이틴 황산염(chondroitin sulfate), 더마탄 황산염(dermatan sulfate), 헤파란 황산염(heparan sulfate), 헤파린(heparin), 케라탄 황산염(keratin sulfate)이 속한다.
글리코사미노글리칸은 이당류 형태의 당이 반복적으로 연결된 구조를 이룬다. 연결되는 당의 갯수는 글리코사미노글리칸마다 다르지만, 수백 개에서 수천 개에 달한다. 글리코사미노글리칸 중에서 히알루론산은 체내 존재량의 절반 이상이 피부에 존재한다. 히알루론산은 세포막에 존재하는 히알루론산 합성효소(hyaluronan synthase)에 의해 합성되며 프로테오글리칸 (proteoglycan)과 결합하지 않고 단독으로 존재하며, 황산기가 없는 유일한 글리코사미노글리칸이다. 다른 글리코사미노글리칸들은 프로테오글리칸과 결합하며 황산기를 가지고 있다. 히알루론산은 글루크론산(glucuronic acid)과 N-아세틸글루코사민(N-acetylglucosamine)이 교차되어 β-1,3 결합과 β-1,4 결합으로 연결되어 있고, 이러한 이당류가 대략 5,000번 반복된다. 인간의 몸에서 대략 1/3 정도(5 g)의 히알루론산은 매일 분해되는 것으로 알려져 있다.
히알루로니다제는 세포외기질(extracellular matrix)에 위치한 히알루론산을 분해하는 효소이다. 인간에는 6 종류의 히알루로니다제 유전자가 존재하는 것으로 알려져 있다 (Hyal1, Hyal2, Hyal3, Hyal4, HyalPS1 그리고 PH20/SPAM1). 인간에서 Hyal1과 Hyal2은 대부분의 조직에서 발현되며, PH20/SPAM1(이하 PH20)은 정자의 세포막과 첨체(acrosome) 막에 발현된다. 그렇지만 HyalPS1은 pseudogene이기 때문에 발현되지 않는다. 히알루로니다제는 히알루론산을 절단하는 방식에 따라 3 종류로 나누어진다. H2O를 사용하여 N-아세틸글루코사민과 글루크론산 사이의 β-1,4 결합을 절단하는 효소(EC 3.2.1.35)와 β-1,3 결합을 절단하는 효소(EC 3.2.1.36), 그리고 H2O를 사용하지 않고 β-1,4 결합을 절단하는 세균의 히알루로니다제(EC 4.2.99.1)로 나누어진다.
Hyal1의 촉매 아미노산 잔기는 D129와 E131이며, substrate-assisted catalysis 방법으로 히알루론산을 가수분해한다. Hyal1은 산성인 pH 3~4에서 최적 활성을 나타내며, pH 4.5 이상에서는 효소 활성이 없다. Hyal1과는 대조적으로, PH20은 pH 3~8의 넓은 pH 구간에서 활성을 나타낸다.
Arming 등은 PH20의 촉매 아미노산이 D111과 E113임을 밝혔다 (Arming et al., 1997). Arming 등은 신호 서열이 제거된 PH20의 첫 번째 아미노산인 Leu를 1번으로 지정하였으므로, 신호 서열이 포함되어 있는 PH20에서는 촉매 아미노산 잔기는 각각 D146과 E148에 해당한다.
히알루로니다제는 히알루론산을 가수분해하여 세포외기질의 히알루론산의 점성(viscosity)을 감소시켜 조직(피부)으로의 투과성(permeability)를 증가시킨다. 피부의 피하 (subcutaneous) 부위는 pH가 대략 7.0 ~ 7.5인 중성이므로, 여러 종류의 히알루로니다제 중에서 PH20이 임상에서 많이 사용되고 있다(Bookbinder et al., 2006). PH20이 임상에서 사용되는 예로는 안과 수술에서 안구이완제 및 마취 주사 첨가제로 이용되고 있고, 항체치료제를 피하 주사할때도 PH20을 병용 투여한다(Bookbinder et al., 2006). 또한 종양세포에 히알루론산이 과발현 되는 특성을 이용하여 PH20으로 종양세포 세포외기질의 히알루론산을 가수분해하여 항암치료제의 종양세포 접근성을 높이는데 사용된다. 또한 조직 내에 과다하게 존재하는 체액 및 혈액의 재흡수를 촉진하는데도 사용된다.
PH20은 Lathrop 등에 의해 기니피그(guinea pig)의 정자에서 처음으로 동정되었고, 다른 많은 종의 정자에도 발현됨이 알려져 있다. 인간의 PH20 유전자는 Lin 등 및 Gmachl 등에 의해 클로닝 되었다. 인간 PH20는 서열번호 1에 따른 서열을 가지는 509개의 아미노산 잔기로 구성되어 있고, 기니피그의 PH20과는 60% 아미노산 서열이 일치한다. 인간의 PH20 효소는 SPAM1 (sperm adhesion molecule-1) 유전자로부터 코딩 되며 정자의 세포막 표면과 첨체의 막 안쪽에 PH20의 Ser490이 glycosylphosphatidylinositol (GPI)과 결합한 형태로 존재한다. 정자는 히알루론산이 많은 난자의 cumulus layer를 통과하여 난자 안으로 침투할 때 PH20을 이용하여 히알루론산을 가수분해한다. PH20은 정자 내 단백질 양의 1% 이내로 존재하며, 6개의 N-당화 자리를 가진다 (N82, N166, N235, N254, N368, N393).
현재 상업적으로 많이 이용되는 PH20은 소나 양의 고환에서 추출한 형태이다. 예로는 암파다제(Amphadase®) (소 히알루로니다제)와 비트라제(Vitrase®) (양 히알루로니다제) 등이 있다.
Bovine testicular hyaluronidase (BTH)는 소의 야생형 PH20에서 신호 펩티드(signal peptide)와 C-말단 56개의 아미노산을 단백질 번역후 변형(post-translational modification) 과정에서 제거한 형태이다. BTH 또한 당 단백질이며 아미노산을 포함한 전체 성분 중 만노오스(mannose)가 5%, 글루코사민(glucosamine)이 2.2%를 차지한다. 동물 유래 히알루로니다제를 인체에 고 용량으로 반복 투여할 경우 중화항체 (neutralizing antibody)가 생성될 수 있다. 동물에서 유래한 히알루로니다제에는 PH20 이외에도 다른 생체물질이 포함되어 있어서, 인체에 투여 시 알러지 반응을 일으키는 원인이 될 수 있다(Bookbinder et al., 2006). 특히 소에서 추출한 PH20의 경우에는 광우병에 대한 우려로 생산과 이용에 제한이 있다. 이러한 문제점을 개선하기 위해 인간PH20의 재조합 단백질에 대한 연구가 진행되었다.
인간 PH20의 재조합 단백질은 효모(P. pastoris), DS-2 곤충세포, 동물세포 등에서 발현된 것이 보고되었다. 곤충세포와 효모에서 생산된 재조합 PH20 단백질은 단백질번역후변형 과정에서 N-당화의 양상이 인간 PH20과 다르다.
히알루로니다제 중에서 단백질 구조가 밝혀진 것은 Hyal1 (PDB ID: 2PE4) (Chao et al., 2007)과 Bee venom hyaluronidase (PDB ID: 1FCQ, 1FCU, 1FCV)가 있다. Hyal1은 촉매 도메인과 EGF-유사 도메인의 2개 도메인으로 구성되어 있으며, 촉매 도메인은 단백질의 2차구조를 특징하는 알파나선과 베타-스트랜드가 각각 8번씩 반복되는 (β/α)8 형태를 이룬다 (Chao et al., 2007). EGF-유사도메인은 Hyal1의 C-말단이 다르게 스플라이싱 된 변이체에서 모두 보존되어 있다. Hyal1과 PH20의 아미노산 서열은 35.1% 일치하며, 아직 PH20의 단백질 구조는 밝혀지지 않았다.
인간 PH20의 재조합 단백질은 Halozyme Therapeutic사에 의해 개발되어 Hylenex 상품명으로 판매되고 있다(Bookbinder et al., 2006; Frost, 2007).
PH20의 촉매 아미노산인 D146과 E148을 각각 아스파라진(D146N)과 글루타민(E148Q)으로 돌연변이시켰을 때 효소 활성이 없었다 (Arming et al., 1997). 또한 PH20의 R246을 글리신으로 치환하면 효소 활성의 90%가 감소하였고, E319를 글루타민, R322을 트레오닌으로 치환하면 효소 활성이 없어졌다. PH20의 C-말단 부위 아미노산 36개가 제거된(474-509 부위의 아미노산 절단) 변이체는 야생형 PH20보다 효소 활성이 75% 감소하였다. 이 돌연변이는 세포 밖으로 분비되지 않고, HeLa 세포 내에 잔존하였다. PH20에서 C-말단 134개 아미노산이 제거되면, PH20의 효소 활성이 없었으며, 세포 밖으로 분비되지 않았다. Frost 등에 의하면 PH20의 C-말단 477-483 부위는 수용성(soluble) 발현에 필수적이다 (Frost, 2007). Full-length PH20 (1~509) 또는 C-말단이 467에서 절단된 변이체의 활성은 C-말단이 477~483 중 한 곳에서 절단된 변이체의 10%에 불과하였다(Frost, 2007).
재조합 PH20은 의학적으로 의약품의 피하 전달을 촉진하기 위한 전달 제제로써의 용도, 안과 질환 환자의 안압을 감소시키는 용도, 수술 후 협착 현상을 지연시키는 용도, 암 등의 질환에서 화학요법제의 활성을 증가시키기 위한 분산 제제로써의 용도, 외과 수술의 보조 치료제 용도 등으로 사용된다.
특히, 단백질 의약품의 경우에는 최근 1mL 당 수십 mg에서 수백 mg으로까지 고농도의 고용량 제품으로 개발되고 있으므로, 이러한 단백질 의약품의 피하 전달을 촉진하기 위한 전달 제제로써의 재조합 PH20의 용도가 증가하고 있다. 이러한 단백질 의약품의 경우에는 고농도로 인한 단백질의 점도 증가 및 응집 현상으로 인하여 물리적 안정성에 문제가 발생할 수 있다. 게다가 단백질의 응집 현상은 비가역적 현상으로 소량이 응집되기 시작하면, 응집이 더욱 증가하는 경향이 있다(Schon et al., 2015). 따라서, 병용 투여하게 되는 재조합 PH20에서 응집 현상이 발생하게 되면 단백질 의약품의 안정성을 감소시킬 수 있는 원인이 된다.
한편, 기존의 재조합 PH20은 여전히 열 안정성이나 발현율이 충분하지 못하다. 따라서, 산업계에서 생물학적 및 물리-화학적 특성을 추가로 개선한 재조합 히알루로니다제에 대한 수요가 매우 높다.
참고문헌
Arming, S., Strobl, B., Wechselberger, C., and Kreil, G. (1997). In vitro mutagenesis of PH-20 hyaluronidase from human sperm. Eur J Biochem 247, 810-814.
Bookbinder, L.H., Hofer, A., Haller, M.F., Zepeda, M.L., Keller, G.A., Lim, J.E., Edgington, T.S., Shepard, H.M., Patton, J.S., and Frost, G.I. (2006). A recombinant human enzyme for enhanced interstitial transport of therapeutics. J Control Release 114, 230-241.
Chao, K.L., Muthukumar, L., and Herzberg, O. (2007). Structure of human hyaluronidase-1, a hyaluronan hydrolyzing enzyme involved in tumor growth and angiogenesis. Biochemistry 46, 6911-6920.
Frost, G.I. (2007). Recombinant human hyaluronidase (rHuPH20): an enabling platform for subcutaneous drug and fluid administration. Expert Opin Drug Deliv 4, 427-440.
Schon, A., Clarkson, B.R., Siles, R., Ross, P., Brown, R.K., Freire, E. (2015) Denatured state aggregation parameters derived from concentration dependence of protein stability. Anal Chem 488, 45-50
WO 2020/022791A (2020. 1. 30.)
본 발명의 목적은 야생형 PH20, 바람직하게는 성숙된 야생형 PH20에 비해 안정성, 효소 활성 및 발현율이 향상된 신규 PH20 변이체 또는 이의 절편을 제공하는 것이다.
본 발명의 다른 목적은 상기 PH20 변이체 또는 이의 절편을 포함하는 암 치료용 조성물 및 이를 이용한 치료방법을 제공하는 것이다.
상기 목적을 달성하기 위하여, 본 발명은 서열번호 3의 아미노산 서열을 갖는 히알루로니다제 변이체에서 하나 이상의 아미노산 잔기의 치환, 결실 및/또는 삽입을 포함하고, 선택적으로 N-말단 및/또는 C-말단의 아미노산 잔기의 일부가 결실된 PH20 변이체 또는 이의 절편을 제공한다.
본 발명은 또한 상기 본 발명에 따른 PH20 변이체 또는 이의 절편을 포함하는 암 치료용 조성물 및 이를 이용한 치료방법을 제공한다.
본 발명에 따른 PH20 변이체 또는 이의 절편들은 성숙된 야생형 PH20과 비교하여 ExpiCHO 세포에서 발현되었을 때 단백질 발현량이 증가하였으며, 단백질 응집온도는 4~11.5 ℃ 정도 증가하여, 높은 열 안정성을 가지면서 또한 효율적으로 생산될 수 있는 효과가 있다.
또한, 본 발명에 따른 PH20 변이체 또는 이의 절편들은 히알루로니다제의 활성을 측정하는 실험 중의 하나인 substrate-gel assay의 결과에서 단백질의 접힘(refolding)이 향상되어 성숙된 야생형 PH20보다 빨리 renaturation이 되는 효과가 있으며, C-말단의 절단위치에 상관없이 원래의 효소 활성을 유지하는 효과가 있다.
나아가 본 발명에 따른 PH20 변이체 또는 이의 절편들은 낮은 면역원성을 가지고 있어, 인체에 반복 투여하는 것이 가능하다.
도 1은 서열번호 3의 아미노산 서열을 가지는 PH20변이체를 기반으로 하는 각종 변이체에 대한 SDS-PAGE 분석 결과를 나타낸 것이다. 이하 각 변이체에 대한 SDS-PAGE 분석 결과는 각 변이체를 발현하는 동물 세포 배양액을 이용하여 컬럼크로마토그래피 방법으로 정제를 진행하고 최종 정제된 변이체에 대하여 10% SDS-PAGE 분석을 실시한 것이다.
도 1A는 변이체 HM98, HM99, HM130, HM143, HM71, HM100, HM131, HM72, HM101, HM114 에 대한 SDS-PAGE 결과를 나타낸 것이다.
도 1B는 변이체 HM63, HM102, HM115, HM64, HM103, HM116, HM125, HM132, HM65, HM133, HM144, HM104, HM117에 대한 SDS-PAGE 결과를 나타낸 것이다.
도 1C는 변이체 HM66, HM105, HM134, HM76, HM106, HM135, HM136, HM67에 대한 SDS-PAGE gel 결과를 나타낸 것이다.
도 1D는 변이체 HM82, HM83, HM84, HM85, HM86, HM88, HM89, HM107, HM118, HM90, HM91, HM92, HM93, HM94, HM95에 대한 SDS-PAGE 결과를 나타낸 것이다.
도 1E는 변이체 HM126, HM69, HM110, HM138, HM73, HM111, HM121, HM139, HM74, HM112, HM140에 대한 SDS-PAGE 결과를 나타낸 것이다.
도 1F는 HM75, HM141, HM145, HM70, HM77, HM142, HM78, HM79, HM96, HM146, HM147, HM149, HM150 변이체에 대한 SDS-PAGE 결과를 나타낸 것이다.
도 2는 성숙된 야생형 PH20과, 성숙된 야생형 PH20의 M345~I361 부위를 각각 Hyal2, Hyal3 및 Hyal4의 대응되는 서열로 치환한 Hyal2-변이체 (Hyal2-Variant), Hyal3-변이체 (Hyal3-Variant) 및 Hyal4-변이체 (Hayl4-Variant)의 발현 정도를 나타낸 것이다. SDS-PAGE의 Lane CS는 배양액 시료, Lane FT는 HisTag 컬럼에서 결합하지 않은 불순물, Lane E는 HisTag 컬럼 용출액이다.
도 3은 서열번호 3의 아미노산 서열을 가지는 PH20변이체를 기반으로 하는 각종 변이체에 대한 SDS-PAGE 분석 결과를 나타낸 것이다. 각 변이체를 발현하는 동물 세포 배양액을 이용하여 컬럼크로마토그래피 방법으로 정제를 진행하고 최종 정제된 변이체에 대하여 10% SDS-PAGE 분석을 실시한 것이다.
도 3A는 변이체 HM152, HM153, HM154, HM155, HM156, HM157, HM158, HM159, HM160, HM161, HM162, HM163, HM164, HM165, HM166, HM167, HM168, HM169에 대한 SDS-PAGE 결과를 나타낸 것이다.
도 3B는 변이체 HM170, HM171, HM172, HM173, HM174, HM175, HM176, HM177, HM178, HM179, HM180, HM181, HM182, HM183, HM184, HM185, HM186에 대한 SDS-PAGE 결과를 나타낸 것이다.
도 3C는 변이체 HM190, HM191, HM192, HM193, HM194, HM195, HM196, HM197, HM198, HM199, HM203, HM204, HM205에 대한 SDS-PAGE 결과를 나타낸 것이다.
도 3D는 변이체 HM208, HM210, HM211, HM212, HM213, HM214, HM216, HM217, HM218, HM219, HM220에 대한 SDS-PAGE 결과를 나타낸 것이다.
도 3E는 변이체 HM231, HM232, HM233, HM234, HM235, HM243, HM245, HM246에 대한 SDS-PAGE 결과를 나타낸 것이다.
도 3F는 변이체 HM254, HM261, HM262, HM263, HM266, HM268, HM271, HM275, HM276, HM279, HM280, HM287, HM288에 대한 SDS-PAGE 결과를 나타낸 것이다.
도 4는 야생형 PH20(L36-Y482)과 서열번호 3의 아미노산 서열을 가지는 PH20변이체(F38-F468)의 열안정성 결과를 SDS-PAGE로 분석한 결과를 나타낸 것이다. Lane A, B, C, D는 초기 상태의 야생형 PH20(Lane A, C)과 서열번호 3의 PH20 변이체(Lane B, D)를 환원 상태(Lane A, B)와 비환원 상태(Lane C, D)로 SDS-PAGE 분석을 실시한 결과이고, Lane E, F, G, H는 42℃ 조건에서 7일 동안 보관한 후 야생형 PH20 (Lane E, G)과 서열번호 3의 PH20 변이체(Lane F, H)를 환원 상태(Lane E, F)와 비환원 상태(Lane G, H)로 SDS-PAGE 분석을 실시한 결과이다.
도 1A는 변이체 HM98, HM99, HM130, HM143, HM71, HM100, HM131, HM72, HM101, HM114 에 대한 SDS-PAGE 결과를 나타낸 것이다.
도 1B는 변이체 HM63, HM102, HM115, HM64, HM103, HM116, HM125, HM132, HM65, HM133, HM144, HM104, HM117에 대한 SDS-PAGE 결과를 나타낸 것이다.
도 1C는 변이체 HM66, HM105, HM134, HM76, HM106, HM135, HM136, HM67에 대한 SDS-PAGE gel 결과를 나타낸 것이다.
도 1D는 변이체 HM82, HM83, HM84, HM85, HM86, HM88, HM89, HM107, HM118, HM90, HM91, HM92, HM93, HM94, HM95에 대한 SDS-PAGE 결과를 나타낸 것이다.
도 1E는 변이체 HM126, HM69, HM110, HM138, HM73, HM111, HM121, HM139, HM74, HM112, HM140에 대한 SDS-PAGE 결과를 나타낸 것이다.
도 1F는 HM75, HM141, HM145, HM70, HM77, HM142, HM78, HM79, HM96, HM146, HM147, HM149, HM150 변이체에 대한 SDS-PAGE 결과를 나타낸 것이다.
도 2는 성숙된 야생형 PH20과, 성숙된 야생형 PH20의 M345~I361 부위를 각각 Hyal2, Hyal3 및 Hyal4의 대응되는 서열로 치환한 Hyal2-변이체 (Hyal2-Variant), Hyal3-변이체 (Hyal3-Variant) 및 Hyal4-변이체 (Hayl4-Variant)의 발현 정도를 나타낸 것이다. SDS-PAGE의 Lane CS는 배양액 시료, Lane FT는 HisTag 컬럼에서 결합하지 않은 불순물, Lane E는 HisTag 컬럼 용출액이다.
도 3은 서열번호 3의 아미노산 서열을 가지는 PH20변이체를 기반으로 하는 각종 변이체에 대한 SDS-PAGE 분석 결과를 나타낸 것이다. 각 변이체를 발현하는 동물 세포 배양액을 이용하여 컬럼크로마토그래피 방법으로 정제를 진행하고 최종 정제된 변이체에 대하여 10% SDS-PAGE 분석을 실시한 것이다.
도 3A는 변이체 HM152, HM153, HM154, HM155, HM156, HM157, HM158, HM159, HM160, HM161, HM162, HM163, HM164, HM165, HM166, HM167, HM168, HM169에 대한 SDS-PAGE 결과를 나타낸 것이다.
도 3B는 변이체 HM170, HM171, HM172, HM173, HM174, HM175, HM176, HM177, HM178, HM179, HM180, HM181, HM182, HM183, HM184, HM185, HM186에 대한 SDS-PAGE 결과를 나타낸 것이다.
도 3C는 변이체 HM190, HM191, HM192, HM193, HM194, HM195, HM196, HM197, HM198, HM199, HM203, HM204, HM205에 대한 SDS-PAGE 결과를 나타낸 것이다.
도 3D는 변이체 HM208, HM210, HM211, HM212, HM213, HM214, HM216, HM217, HM218, HM219, HM220에 대한 SDS-PAGE 결과를 나타낸 것이다.
도 3E는 변이체 HM231, HM232, HM233, HM234, HM235, HM243, HM245, HM246에 대한 SDS-PAGE 결과를 나타낸 것이다.
도 3F는 변이체 HM254, HM261, HM262, HM263, HM266, HM268, HM271, HM275, HM276, HM279, HM280, HM287, HM288에 대한 SDS-PAGE 결과를 나타낸 것이다.
도 4는 야생형 PH20(L36-Y482)과 서열번호 3의 아미노산 서열을 가지는 PH20변이체(F38-F468)의 열안정성 결과를 SDS-PAGE로 분석한 결과를 나타낸 것이다. Lane A, B, C, D는 초기 상태의 야생형 PH20(Lane A, C)과 서열번호 3의 PH20 변이체(Lane B, D)를 환원 상태(Lane A, B)와 비환원 상태(Lane C, D)로 SDS-PAGE 분석을 실시한 결과이고, Lane E, F, G, H는 42℃ 조건에서 7일 동안 보관한 후 야생형 PH20 (Lane E, G)과 서열번호 3의 PH20 변이체(Lane F, H)를 환원 상태(Lane E, F)와 비환원 상태(Lane G, H)로 SDS-PAGE 분석을 실시한 결과이다.
다른 식으로 정의되지 않는 한, 본 명세서에서 사용된 모든 기술적 및 과학적 용어들은 본 발명이 속하는 기술분야에서 숙련된 전문가에 의해서 통상적으로 이해되는 것과 동일한 의미를 갖는다. 일반적으로, 본 명세서에서 사용된 명명법은 본 기술분야에서 잘 알려져 있고 통상적으로 사용되는 것이다.
본 발명에 있어, 야생형 PH20을 기준으로 설명할 때의 각 변이체의 아미노산 잔기의 위치는 서열번호 1에 따른 아미노산 서열의 위치에 따르며, 서열번호 3에 따른 PH20 변이체를 기준으로 설명할 경우에는 서열번호 3의 아미노산 서열의 위치에 따른다.
본 발명의 발명자들은 앞선 연구를 통해 서열번호 1의 아미노산 서열을 갖는 야생형 PH20, 바람직하게는 성숙된 야생형 PH20에 있어, 알파나선 부위 및/또는 그 연결 부위에 해당하는 부위, 바람직하게는 알파나선 8 부위(S347~C381) 및/또는 알파나선 7과 알파나선 8 연결 부위(A333~R346)에서 하나 이상의 아미노산 잔기의 치환을 포함하고, 선택적으로 N-말단 및/또는 C-말단의 아미노산 잔기 일부가 절단되어 결실된 히알루로니다제 PH20 변이체가 기존의 야생형 PH20 또는 그 절편에 비해 우수한 효능을 갖는다는 것을 발견하고, 특허출원한 바 있다(WO 2020/022791A 참조).
본 발명에 있어, “성숙된 야생형 PH20”은 서열번호 1의 야생형 PH20의 아미노산 서열에서, 시그널 펩타이드인 M1 내지 T35와, PH20의 실질적인 기능과는 무관한 N483 내지 L509 또는 A491 내지 L509가 결실된, 서열번호 1의 L36 내지 Y482 또는 L36 내지 S490의 아미노산 잔기로 이루어진 단백질을 의미한다.
구체적으로 본 발명의 발명자들은 선행연구를 통해 서열번호 1의 아미노산 서열을 갖는 야생형 PH20에 있어 알파나선 8 부위(S347~C381) 및/또는, 알파나선 7과 알파나선 8 연결 부위(A333~R346) 중의 일부인 T341 내지 I361에 해당하는 아미노산 부위를 서열번호 2의 서열을 갖는 야생형 Hyal1의 대응되는 아미노산 잔기들로 치환할 경우, 발현 효율 및 효소 활성이 향상된다는 것을 발견하였으며, 나아가 N-말단 및 C-말단에서의 일부 아미노산 서열이 결실된 단편의 경우에도 여전히 우수한 발현 효율 및 높은 효소 활성을 가진다는 점을 확인한 바 있다.
본 발명의 연구자들은 지속적으로 연구를 수행한 결과, 서열번호 1의 아미노산 서열을 갖는 야생형 PH20의 T341 내지 I361에 해당하는 아미노산 부위를 서열번호 2의 서열을 갖는 야생형 Hyal1의 대응되는 아미노산 서열로 치환된 서열번호 3의 서열을 갖는 변이체의 경우, 추가적인 아미노산 잔기의 치환, 결실 및/또는 삽입을 포함하고, 나아가 선택적으로 N-말단 및/또는 C-말단의 아미노산 잔기의 일부가 결실되더라도 여전히 우수한 발현 효율 및 높은 효소 활성을 가질 뿐만 아니라, 단백질 응집온도(aggregation temperature, Tagg)가 야생형 PH20에 비해 현저하게 향상되는 것을 발견하고 본 발명을 완성하였다.
서열번호 3의 서열을 갖는 변이체는 서열번호 1의 아미노산 서열을 갖는 야생형 PH20에서 T341S, L342W, S343E, I344N, M345T, S347T, M348K, K349E, L352Q, L353A, L354I, D355K, N356E, E359D 및 I361T의 15개의 아미노산 잔기가 치환된 변이체이다.
이러한 측면에서, 본 발명에 따른 PH20 변이체 또는 이의 절편은 서열번호 3의 아미노산 서열을 갖는 PH20 변이체에서 하나 이상의 아미노산 잔기의 치환, 결실 및/또는 삽입을 포함하고, 선택적으로 N-말단 및/또는 C-말단의 아미노산 잔기의 일부가 결실된 것을 특징으로 한다.
앞서 설명한 바와 같이, 서열번호 3의 아미노산 서열을 갖는 변이체는 야생형 PH20의 T341 내지 I361의 아미노산 잔기들이 야생형 Hyal1의 대응되는 아미노산 잔기들로 치환된 변이체이다(표 2 참조). 서열번호 3의 아미노산 서열을 갖는 변이체 또는 이의 N-말단 및 C-말단에서의 아미노산 잔기 결실을 포함하는 단편은 기존 연구에서 야생형 PH20에 비해 가장 뛰어난 활성과 안정성을 가지고 있는 변이체로 확인되었다.
구체적으로, 본 발명에 따른 PH20 변이체 또는 이의 절편은, 서열번호 3의 서열에 있어서, 하나 이상의 변이, 바람직하게는 아미노산 잔기의 치환, 결실 및/또는 삽입을 포함하는 것을 특징으로 하며, 단백질의 안정성을 나타내는 지표인 단백질의 응집 온도(aggregation temperature, Tagg)가 야생형 PH20보다 높은 것을 특징으로 한다. 또한, 본 발명에 따른 PH20 변이체는 서열번호 1의 야생형 PH20은 포함하지 않는다.
본 발명에 있어, “PH20 변이체”는 서열번호 3의 아미노산 서열에서 일부 아미노산 잔기의 변이, 바람직하게는 아미노산 잔기의 치환, 결실 및/또는 삽입을 포함하는 것뿐 아니라, 그러한 아미노산 잔기의 치환, 결실 및/또는 삽입과 함께, N-말단 또는 C-말단에서의 일부 아미노산 잔기의 결실이 일어난 것을 모두 포함하는 개념으로 사용되며, “PH20 변이체 또는 이의 절편”이라는 표현과 실질적으로 동일한 개념으로 사용된다.
바람직하게는 본 발명에 따른 PH20 변이체는 서열번호 3의 아미노산 서열을 갖는 변이체에 있어, R39, D65 내지 L68, N82, T84, I102 내지 I105, T132 내지 Y134, N166, L179 내지 T182, T185 내지 K187, V241 내지 K244, N266 내지 Q269, P271, V272, K290 내지 P292, Q311 내지 K314, G340 내지 N363, L441, S442, D451 내지 D453, D461, V463 및 D461 내지 V463로 구성된 군에서 선택된 하나 이상의 위치에서 아미노산 잔기의 치환, 삽입 및/또는 결실을 포함하는 것을 특징으로 하며 단백질 응집온도(aggregation temperature, Tagg)가 야생형 PH20보다 향상된 것, 즉 높은 것을 특징으로 한다.
본 발명에 따른 PH20 변이체는 서열번호 3의 아미노산 서열에서 20개 이하, 바람직하게는 17개 이하, 더욱 바람직하게는 15개 이하의 아미노산 위치에서의 변이를 포함할 수 있지만 이에 한정되는 것은 아니다.
더욱 바람직하게는 본 발명에 따른 PH20 변이체 변이체 또는 이의 절편은 서열번호 3의 아미노산 서열을 갖는 변이체에 있어, R39K, D65A, E66A, P67A, L68A, N82A, T84N, I102A, D103A, S104A, S104N, I105A, I105Q, T132A, T132S, F133A, Y134A, N166A, N166K, L179A, L179S, L179I, L179F, S180T, S180A, L181A, L181M, T182A, T185A, E186A, E186D, K187A, V241A, E242A, I243A, K244A, N266A, T267A, Q268A, Q268D, Q268I, Q268N, Q269A, P271A, V272A, K290A, I291A, I291G, I291L, P292A, P292D, Q311A, V312A, L313A, L313P, L313M, K314A, G340Q, S341H, S341D, S341T, W342I, W342D, W342H, W342L, E343V, E343S, E343Y, E343Q, N344F, N344I, T345E, T345K, T345S, R346M, R346F, R346L, R346T, R346S, R346A, T347Q, T347E, T347V, T347W, T347H, T347S, K348Q, K348F, K348D, K348T, K348E, K348M, E349L, E349W, E349A, S350Q, S350I, S350D, S350T, S350E, S350N, Q352E, Q352G, Q352Y, Q352W, Q352T, A353E, A353Y, A353H, A353K, I354E, I354Q, I354S, I354V, I354A, I354N, I354T, I354R, I354W, I354L, K355Q, K355H, K355D, E356M, E356F, E356I, E356L, E356Q, E356V, E356D, Y357W, Y357F, M358V, M358R, M358Y, M358L, D359K, D359V, D359Y, D359Q, D359T, D359S, D359E, T360Y, T360R, T360L, T360D, T360S, T361M, T361E, T361H, T361L, T361D, T361I, L362A, N363M, N363E, L441A, S442A, D451A, D451S, T452A, T452D, T452H, T452K, T452G, T452P, T452M, T452F, D453A, D461R, D461A, G462A, V463Y 및 V463A로 구성된 군에서 선택된 하나 이상의 아미노산 잔기의 치환을 포함하는 것을 특징으로 하지만 이에 한정되는 것은 아니다.
본 발명에 있어서, “S341”과 같이 1 글자(one letter)의 아미노산 잔기명과 숫자가 함께 기재된 표현은 서열번호 1 또는 서열번호 3에 따른 아미노산 서열에서의 각 위치에서의 아미노산 잔기를 의미한다.
예를 들어 “S341”은 서열번호 3의 아미노산 서열에서의 341번째 위치에서의 아미노산 잔기가 세린임을 의미하며, “S341H”는 서열번호 3의 341번째 세린이 히스티딘으로 치환된 것을 의미한다.
본 발명에 따른 PH20 변이체 또는 이의 절편은, 특정 아미노산 잔기 위치에서, 아미노산 잔기가 보존적으로 치환된 변이체 또는 이의 절편들도 포함하는 의미로 해석된다.
본 명세서에서 “보존적 치환”이란 1개 이상의 아미노산을 해당 PH20 변이체의 생물학적 또는 생화학적 기능의 손실을 야기하지 않는 유사한 생화학적 특성을 갖는 아미노산으로 치환하는 것을 포함하는 PH20 변이체의 변형을 의미한다.
“보존적 아미노산 치환”은 아미노산 잔기를 유사한 측쇄를 갖는 아미노산 잔기로 대체시키는 치환이다. 유사한 측쇄를 갖는 아미노산 잔기 부류는 해당 기술분야에 규정되어 있으며, 잘 알려져 있다. 이들 부류는 염기성 측쇄를 갖는 아미노산(예를 들어, 라이신, 아르기닌, 히스티딘), 산성 측쇄를 갖는 아미노산(예를 들어, 아스파르트산, 글루탐산), 대전되지 않은 극성 측쇄를 갖는 아미노산(예를 들어, 아스파라진, 글루타민, 세린, 트레오닌, 티로신, 시스테인), 비극성 측쇄를 갖는 아미노산(예를 들어, 글리신, 알라닌, 발린, 류신, 이소류신, 프롤린, 페닐알라닌, 메티오닌, 트립토판), 베타-분지된 측쇄를 갖는 아미노산(예를 들어, 트레오닌, 발린, 이소류신) 및 방향족 측쇄를 갖는 아미노산(예를 들어, 티로신, 페닐알라닌, 트립토판, 히스티딘)을 포함한다.
본 발명의 PH20 변이체 또는 이의 절편은 보존적 아미노산 치환을 갖더라도 여전히 활성을 보유할 수 있음이 확인되었다.
또한, 본 발명에 따른 PH20 변이체 또는 이의 절편은, 본 발명에 따른 PH20 변이체 또는 이의 절편과 실질적으로 동일한 기능 및/또는 효과를 가지며, 80% 또는 85% 이상, 바람직하게는 90% 이상, 더욱 바람직하게는 95% 이상, 가장 바람직하게는 99% 이상의 아미노산 서열 상동성을 가지는 PH20 변이체 또는 이의 절편들도 포함하는 의미로 해석된다.
본 발명에 따른 PH20 변이체 또는 이의 절편들은 성숙된 야생형 PH20보다 동물세포에서 발현이 증가하며, 단백질 접힘도 증가하여 열 안정성이 증가하는 효과를 나타내며, 나아가 열 안정성이 증가함에도 불구하고, 이들의 효소 활성은 성숙된 야생형 PH20보다 증가하거나 유사하였다.
한편, 성숙된 야생형 PH20의 C-말단 부위가 절단되면 효소 활성이 감소하는 것으로 알려져 있으나, 본 발명에 따른 PH20 변이체들은 단백질 접힘 증가와 열 안정성 증가로 인하여 C-말단에서의 일부 아미노산 잔기가 절단되어 결실되거나, 및/또는 N-말단의 아미노산이 1~7개, 바람직하게는 1~5개까지 절단되어 결실되더라도 성숙된 야생형 PH20보다 증가하거나 유사한 효소 활성 및 발현효율을 유지하였으며, 또한 높은 단백질의 응집 온도(aggregation temperature, Tagg)를 가진다.
이에 따라 본 발명에 따른 PH20 변이체 또는 이의 절편은, 서열번호 3 등의 본 발명에 따른 아미노산 서열을 갖는 변이체에 있어서, 하나 이상의 변이, 바람직하게는 아미노산 잔기의 치환, 결실 및/또는 삽입을 포함하며, 추가적으로 C-말단 및/또는 N-말단에서의 일부 아미노산 잔기가 결실된 것을 특징으로 하지만, 이에 한정되는 것은 아니다.
한 측면에서, 본 발명에 따른 PH20 변이체 또는 이의 절편은, 서열번호 3 등의 본 발명에 따른 아미노산 서열 N-말단의 M1 내지 P42로 구성된 군에서 선택된 아미노산 잔기의 앞, 바람직하게는 L36, N37, F38, R39, A40, P41 또는 P42의 아미노산 잔기 앞에서의 절단이 일어나 N-말단에서의 일부 아미노산 잔기가 결실되거나, 및/또는 C-말단의 V455 내지 L509로 구성된 군에서 선택된 아미노산 잔기 다음, 바람직하게는 V455 내지 S490로 구성된 군에서 선택된 아미노산 잔기 다음, 가장 바람직하게는 V455, D456, C458, D461, C464, I465, D466, A467, F468, K470, P471, P472, M473, E474, T475, E476, P478, I480, Y482, A484, P486, T488 또는 S490의 아미노산 잔기 다음에서의 절단이 일어나 C-말단에서의 일부 아미노산 잔기가 결실된 것을 특징으로 할 수 있다.
상기 N-말단의 M1 내지 P42로 구성된 군에서 선택된 아미노산 잔기의 앞에서의 절단이 일어났다는 표현은 N-말단의 M1 내지 P42에서 선택된 아미노산 잔기의 바로 앞 아미노산 잔기까지가 절단되어 결실되었다는 의미이다. M1 앞에서의 절단이 일어난 경우는 아무런 N-말단에서의 절단이 일어나지 않은 경우를 의미한다.
예를 들어, L36, N37, F38, R39, A40, P41 또는 P42의 아미노산 잔기 앞에서의 절단이 일어났다는 표현은, 각각 서열번호 3 등의 본 발명에 따른 아미노산 서열에서 M1부터 L36의 바로 앞 아미노산 잔기인 T35까지, M1부터 N37의 바로 앞 아미노산 잔기인 L36까지, M1부터 F38의 바로 앞 아미노산 잔기인 N37까지, M1부터 R39의 바로 앞 아미노산 잔기인 F38까지, M1부터 A40의 바로 앞 아미노산 잔기인 R39까지, M1부터 P41의 바로 앞 아미노산 잔기인 A40까지, M1부터 P42의 바로 앞 아미노산 잔기인 P41까지가 절단되어 제거되었다는 것을 의미한다.
또한, C-말단의 V455 내지 L509로 구성된 군에서 선택된 아미노산 잔기 다음에서 절단이 일어났다는 표현은 C-말단의 V455 내지 L509에서 선택된 아미노산 잔기의 바로 다음 아미노산 잔기부터 절단되어 결실되었다는 의미이다.
예를 들어, C-말단의 V455, D456, C458, D461, C464, I465, D466, A467, F468, K470, P471, P472, M473, E474, T475, E476, P478, I480, Y482, A484, P486, T488 또는 S490의 아미노산 잔기 다음에서의 절단이 일어났다는 표현은 각각 서열번호 3 등의 본 발명에 따른 아미노산 서열에서 상기 V455, D456, C458, D461, C464, I465, D466, A467, F468, K470, P472, M473, E474, T475, E476, P478, I480, Y482, A484, P486, T488 또는 S490 다음 아미노산 잔기부터 절단되어 제거되었음을 의미한다.
바람직하게는 본 발명에 따른 신규 PH20 변이체 또는 이의 절편은 서열번호 3의 아미노산 서열을 갖는 변이체에 있어, 하나 이상의 위치에서의 아미노산 잔기의 치환, 삽입 또는 결실을 포함하고, N-말단의 F38 잔기 앞에서 절단되고, C-말단의 F468 잔기 다음에서 절단된 것을 특징으로 한다.
보다 바람직하게는, 본 발명에 따른 신규 PH20 변이체 또는 이의 절편은 서열번호 163 내지 서열번호 316로 구성된 군에서 선택되는 아미노산 서열을 포함하는 것을 특징으로 하지만, 이에 한정되는 것은 아니다.
본 발명에 따른 구체적 실시예에서 제작한 PH20 변이체에서 치환 또는 절단된 아미노산의 서열은 표 6에 기재된 바와 같다.
또한, 본 발명에서는 PH20의 고유한 신호 펩티드가 아닌 동물세포에서 단백질 발현량이 많은 다른 단백질의 신호 펩티드를 이용하여 재조합 PH20 단백질의 발현을 향상시키고자 하였다.
이에 따라 또 다른 측면에서, 본 발명에 따른 신규 PH20 변이체는 M1 내지 T35의 야생형 PH20의 신호 펩티드를 대신하여, 추가적으로 N-말단에 표 3에 기재된 바와 같은 서열번호 4에 따른 MATGSRTSLLLAFGLLCLPWLQEGSA의 아미노산 서열을 갖는 인간 성장호르몬 유래의 신호 펩티드, 서열번호 5에 따른 MKWVTFISLLFLFSSAYS의 아미노산 서열을 갖는 인간 혈청 알부민 유래의 신호 펩티드, 또는 서열번호 6에 따른 MAAHLLPICALFLTLLDMAQG의 아미노산 서열을 갖는 인간 Hyal1 유래의 신호 펩티드를 포함하는 것을 특징으로 하지만, 이에 한정되는 것은 아니다.
상기 “M1 내지 T35의 야생형 PH20의 신호 펩티드를 대신”한다는 의미는 서열번호 3의 아미노산 서열에 있어, 신호 펩티드의 일부 또는 전부가 결실되어 야생형 PH20의 신호 펩티드의 기능을 수행하지 못하는 경우를 의미하며, 추가적으로 N-말단의 일부가 더 결실된 경우, 예를 들어 N37, F38, R39, A40, P41 또는 P42 잔기 앞에서의 절단이 일어나 야생형 PH20의 신호 펩티드와 함께 추가적인 N-말단의 결실이 일어난 경우를 포함하는 의미로 사용된다.
본 발명은 다른 측면에서, 본 발명에 따른 신규 PH20 변이체 또는 절편을 포함하는 암 치료용 조성물 및 이를 이용한 암 치료방법을 제공한다.
본 발명에 따른 신규 PH20 변이체 또는 절편으로 치료가능한 암 또는 암종은 특별히 제한되지 않으며, 고형암 및 혈액암을 모두 포함한다. 이러한 암의 예로는 흑색종 등의 피부암, 간암, 간세포암(hepatocellular carcinoma), 위암, 유방암, 폐암, 난소암, 기관지암, 비인두암, 후두암, 췌장암, 방광암, 대장암, 결장암, 자궁경부암, 뇌암, 전립선암, 골암, 갑상선암, 부갑상선암, 신장암, 식도암, 담도암, 고환암, 직장암, 두경부암, 경추암, 요관암, 골육종, 신경아세포종, 섬유육종, 횡문근육종, 성상세포종, 신경모세포종 및 신경교종으로 이루어진 군에서 선택될 수 있지만, 이에 한정되는 것은 아니다. 바람직하게는 본 발명의 조성물로 치료할 수 있는 암은 대장암, 유방암, 폐암 및 신장암으로 구성된 군에서 선택될 수 있지만, 이에 한정되는 것은 아니다.
상기 조성물은 약학 조성물일 수 있다. 상기 약학 조성물은 약학적으로 허용 가능한 조성물을 추가로 포함할 수 있으며, 상기 조성물은 약물의 제제화에 통상적으로 이용되는 것으로서, 락토스, 덱스트로스, 수크로스, 솔비톨, 만니톨, 전분, 아카시아 고무, 인산칼슘, 알기네이트, 젤라틴, 규산 칼슘, 미세결정성 셀룰로스, 폴리비닐피롤리돈, 셀룰로스, 물, 시럽, 메틸 셀룰로스, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 활석, 스테아르산 마그네슘, 미네랄 오일 등으로 이루어진 군에서 선택된 1종 이상일 수 있으나, 이에 한정되는 것은 아니다. 상기 약학 조성물은 또한 약학 조성물 제조에 통상적으로 사용되는 희석제, 부형제, 윤활제, 습윤제, 감미제, 향미제, 유화제, 현탁제, 보존제로 이루어진 군에서 선택된 1종 이상을 추가로 포함할 수 있다.
상기 약학 조성물은 경구 또는 비경구로 투여할 수 있다. 비경구 투여인 경우에는 정맥내 주입, 피하 주입, 근육 주입, 복강 주입, 내피 투여, 국소 투여, 비내 투여, 폐내 투여 및 직장내 투여 등으로 투여할 수 있다. 경구 투여 시, 단백질 또는 펩타이드는 소화가 되기 때문에 경구용 조성물은 활성 약제를 코팅하거나 위에서의 분해로부터 보호되도록 제형화될 수 있다. 또한, 상기 조성물은 활성 물질이 표적 세포로 이동할 수 있는 임의의 장치에 의해 투여될 수 있다.
상기 약학 조성물은 오일 또는 수성 매질중의 용액, 현탁액, 시럽제 또는 유화액 형태이거나 엑스제, 산제, 분말제, 과립제, 정제 또는 캅셀제 등의 형태로 제형화될 수 있으며, 제형화를 위하여 분산제 또는 안정화제를 추가적으로 포함할 수 있다.
특히, 본 발명에 따른 암 치료용 조성물은 다른 항암제와의 병용 치료 용도로 사용되는 것을 특징으로 한다.
본 발명에 따른 신규 PH20 변이체 또는 절편과 병용 치료 용도로 사용가능한 항암제는 화학항암제, 항체 형태의 항암제, 생물학적 항암제, RNAi, 세포 치료제 등이 바람직하지만 이에 한정되는 것은 아니다.
바람직하게는 본 발명에 따른 신규 PH20 변이체 또는 절편과 병용 치료 용도로 사용가능한 항암제는 면역항암제, 특히 바람직하게는 면역체크포인트 저해제(immune checkpoint inhibitor)이지만 이에 한정되는 것은 아니다.
또한 본 발명은 본 발명에 다른 신규 PH20 변이체 또는 절편과 다른 항암제, 특히 상기의 항암제들을 병용하여 사용하는 것을 특징으로 하는 암 치료 방법을 제공한다.
본 발명은 다른 관점에서, 본 발명에 따른 PH20 변이체 또는 이의 절편을 코딩하는 핵산에 관한 것이다.
본 명세서에서 사용되는 핵산은 세포, 세포 용해물(lysate) 중에 존재하거나, 또는 부분적으로 정제된 형태 또는 실질적으로 순수한 형태로 존재할 수도 있다. 핵산은 알칼리/SDS 처리, CsCl 밴드화(banding), 컬럼 크로마토그래피, 아가로스 겔 전기 영동 및 해당 기술분야에 잘 알려진 기타의 것을 포함하는 표준 기술에 의해 다른 세포 성분 또는 기타 오염 물질, 예를 들어 다른 세포의 핵산 또는 단백질로부터 정제되어 나올 경우 "단리"되거나 "실질적으로 순수하게 된" 것이다. 본 발명의 핵산은 예를 들어 DNA 또는 RNA일 수 있다.
본 발명은 또 다른 관점에서, 상기 핵산을 포함하는 벡터에 관한 것이다. 본 발명에 따른 PH20 변이체 또는 이의 절편의 발현을 위하여, PH20 변이체 또는 이의 절편을 코딩하는 DNA를 표준 분자 생물학 기술(예를 들어 PCR 증폭 또는 PH20 변이체를 발현하는 하이브리도마를 사용한 cDNA 클로닝)로 수득할 수 있으며, DNA가 전사 및 번역 제어 서열에 "작동되도록 결합"되어 발현 벡터 내로 삽입될 수 있다.
본 명세서에서 사용되는 용어 "작동되도록 결합"은 벡터 내의 전사 및 번역 제어 서열이 PH20 변이체 또는 이의 절편을 코딩하는 유전자의 전사 및 번역을 조절하는 의도된 기능을 하도록 PH20 변이체 또는 이의 절편을 코딩하는 유전자가 벡터 내로 라이게이션된다는 것을 의미할 수 있다. 발현 벡터 및 발현 제어 서열은 사용되는 발현용 숙주세포와 적합하도록 선택된다. PH20 변이체를 코딩하는 유전자는 표준 방법(예를 들어 PH20 변이체 또는 이의 절편을 코딩하는 유전자 단편 및 벡터 상의 상보성 제한 효소 부위의 라이게이션, 또는 제한 효소 부위가 전혀 존재하지 않을 경우 블런트 엔드 라이게이션(blunt end ligation)으로 발현 벡터 내로 삽입된다.
또한, 상기 재조합 발현 벡터는 숙주세포에서 PH20 변이체 또는 이의 절편을 코딩하는 유전자의 발현을 제어하는 조절서열을 지닌다. "조절서열"은 PH20 변이체 또는 이의 절편을 코딩하는 유전자의 전사 또는 번역을 제어하는 프로모터, 인핸서 및 기타 발현 제어 요소(예를 들어 폴리아데닐화 신호)를 포함할 수 있다. 통상의 기술자는 형질전환시킬 숙주세포의 선택, 단백질의 발현 수준 등과 같은 인자에 따라 조절 서열을 달리 선택하여, 발현 벡터의 디자인이 달라질 수 있음을 인식할 수 있다.
본 발명은 또 다른 관점에서, 상기 핵산 또는 상기 벡터를 포함하는 숙주세포에 관한 것이다. 본 발명에 따른 숙주 세포는 동물세포, 식물세포, 효모, 대장균 및 곤충세포로 구성된 군에서 선택되는 것이 바람직하지만, 이에 한정되는 것은 아니다.
구체적으로는 본 발명에 따른 숙주세포는 대장균, 바실러스 서브틸리스(Bacillus subtilis), 스트렙토마이세스 속(Streptomyces sp.), 슈도모나스 속(Pseudomonas sp.), 프로테우스 미라빌리스(Proteus mirabilis) 또는 스타필로코쿠스 속(Staphylococcus sp.)과 같은 원핵 세포일 수 있다. 또한, 아스페르길러스 속(Aspergillus sp.)과 같은 진균, 피치아 파스토리스(Pichia pastoris), 사카로마이세스 세레비지애(Saccharomyces cerevisiae), 쉬조사카로마세스 속(Schizosaccharomyces sp.) 및 뉴로스포라 크라사(Neurospora crassa)와 같은 효모, 그 밖의 하등진핵 세포, 및 곤충으로부터의 세포와 같은 고등 진핵생물의 세포와 같은 진핵 세포일 수 있다.
또한, 본 발명에 따른 숙주세포는 식물이나 포유동물로부터 유래할 수 있다. 바람직하게는, 원숭이 신장 세포7(COS7: monkey kidney cells) 세포, NSO 세포, SP2/0, 차이니즈 햄스터 난소(CHO: Chinese hamster ovary) 세포, W138, 어린 햄스터 신장(BHK: baby hamster kidney) 세포, MDCK, 골수종 세포주, HuT 78 세포 및 HEK293 세포 등이 이용가능하지만 이에 한정되지 않는다. 특히 바람직하게는 CHO 세포가 사용될 수 있다.
상기 핵산 또는 상기 벡터는 숙주세포에 형질주입 또는 트랜스펙션(transfection)된다. "형질주입" 또는 "트랜스펙션”시키기 위해 원핵 또는 진핵 숙주세포 내로 외인성 핵산(DNA 또는 RNA)을 도입하는 데에 통상 사용되는 여러 종류의 다양한 기술, 예를 들어 전기 영동법, 인산칼슘 침전법, DEAE-덱스트란 트랜스펙션 또는 리포펙션(lipofection) 등을 사용할 수 있다. 본 발명에 따른 PH20 변이체 또는 이의 절편을 발현시키기 위해 다양한 발현 숙주/벡터 조합이 이용될 수 있다. 진핵숙주에 적합한 발현 벡터로는 이들로 한정되는 것은 아니지만 SV40, 소 유두종바이러스, 아데노바이러스, 아데노-연관 바이러스(adeno-associated virus), 시토메갈로바이러스 및 레트로바이러스로부터 유래된 발현 조절 서열이 포함된다. 세균 숙주에 사용할 수 있는 발현 벡터에는 pET, pRSET, pBluescript, pGEX2T, pUC벡터, col E1, pCR1, pBR322, pMB9 및 이들의 유도체와 같이 대장균(Escherichia coli)에서 얻어지는 세균성 플라스미드, RP4와 같이 보다 넓은 숙주 범위를 갖는 플라스미드, λgt10과 λgt11, NM989와 같은 매우 다양한 파지 람다(phage lambda) 유도체로 예시될 수 있는 파지 DNA, 및 M13과 필라멘트성 단일가닥의 DNA 파지와 같은 기타 다른 DNA 파지가 포함된다. 효모 세포에 유용한 발현 벡터는 2μm 플라스미드 및 그의 유도체이다. 곤충 세포에 유용한 벡터는 pVL941이다.
본 발명은 또 다른 관점에서, 숙주세포를 배양하여 본 발명에 따른 PH20 변이체 또는 이의 절편을 발현시키는 단계를 포함하는 본 발명에 따른 PH20 변이체 또는 이의 절편의 제조방법에 관한 것이다.
상기 PH20 변이체 또는 이의 절편을 발현할 수 있는 재조합 발현 벡터가 포유류 숙주세포 내로 도입될 경우, PH20 변이체 또는 이의 변이체는 숙주세포에서 발현되기에 충분한 기간 동안, 또는 더 바람직하게는 숙주세포가 배양되는 배양 배지 내로 PH20 변이체가 분비되게 하기에 충분한 기간 동안 숙주세포를 배양함으로써 제조될 수 있다.
경우에 따라서, 발현된 PH20 변이체 또는 이의 절편은 숙주세포로부터 분리하여 균일하도록 정제할 수 있다. 상기 PH20 변이체 또는 이의 절편의 분리 또는 정제는 통상의 단백질에서 사용되고 있는 분리, 정제 방법, 예를 들어 크로마토그래피에 의해 수행될 수 있다. 상기 크로마토그래피는 예를 들어, 친화성 크로마토그래피, 이온교환 크로마토그래피 또는 소수성 크로마토그래피에서 선택된 하나 이상의 조합일 수 있지만, 이에 한정되지는 않는다. 상기 크로마토그래피 이외에, 추가로 여과, 초여과, 염석, 투석 등을 조합하여 사용할 수 있다.
효소의 산업적 이용 가능성을 확인하기 위하여서는 효소의 촉매 반응 속도에 대한 분석이 필요하다. 효소 반응은 고정된 반응성의 활성 부위를 갖는 효소 반응과 다양한 반응성을 가진 여러 활성 부위를 갖는 효소 반응으로 나뉠 수 있다. 히알루로니다제와 같이 고정된 반응성의 단일 활성 부위를 갖는 효소의 촉매 반응의 속도는 Michaelis-Menten의 속도 공식에 따르는 것으로 알려져 있다.
Michaelis-Menten의 효소 반응 속도론은 다음의 식과 같이 효소(E) - 기질(S)의 복합체[ES] 형성단계에서의 가역 반응 단계와 ES 복합체의 해리로 인한 생성물(P)가 생성되는 비가역 반응 단계의 2단계 반응체계로 효소 반응을 가정하는 것을 전제로 한다. 이 경우, kf, kr, kcat은 각 방향으로의 반응의 속도 상수이다 (Alan Fersht (1977) Enzyme structure and mechanism).
효소 반응은 효소와 기질이 반응하여 ES 복합체를 형성하는 과정이 빠르게 평형 상태로 도달한다고 가정하거나, 충분히 높은 기질 농도를 유지하는 반응을 수행하여 효소의 농도를 충분히 낮게 하여 d[ES]/dt≒0이라 가정할 수 있는 유사 정상상태라고 할 수 있다. 빠른 평형을 가정하거나 유사 정상상태를 가정하는 속도식은 모두 동일하게 유도되기 때문에, 대부분의 실험은 초기에 효소농도에 비해 높은 기질농도를 유지하는 유사 정상상태로 가정한다.
이와 같은 가정하에서 “효소의 양은 반응 전후에 일정하다.”와 “”화학 반응에서 화학 평형점에 도달할 경우, 생성물이 만들어지는 반응속도와 이 물질이 다시 분해되는 속도는 같다.”라는 조건을 이용하면, 최종 생성물의 반응 속도는 다음과 같은 Michaelis-Menten 속도 공식으로 표현할 수 있다. 이 때, K M = (k r + k cat ) / k f 이며, Vmax = k cat [E]0이다.
이와 같은 Michaelis-Menten 속도 공식을 이용하여 효소 반응 속도의 분석을 실험적으로 수행하기 위하여서 Lineweaver-Burk 방정식을 이용한다. 이 방정식은 실험에서 주어진 기질 농도의 역수 1/[S]에 대해 실험적으로 측정한 반응속도의 역수 1/V의 값과의 관계를 보여주는 방정식이다. 이 방정식이 1차 방정식임을 통계적으로 확인하게 되면, 효소 반응이 Michaelis-Menten의 속도 공식에 따르는 반응임을 확인할 수 있으며, 이 방정식을 이용하여 K M 과 Vmax 를 구할 수 있다.
효소는 화학 반응을 촉매하는데 있어, 활성 부위에서 기질과 결합한 후 전이 상태를 갖게 되는데, 높은 에너지를 갖는 전이 상태로 도달하기 위한 활성화 에너지는 기질과의 여러 결합을 통하여 낮아지게 된다. 이러한 전이 상태로 도달하기 위한 평형 상수는 k cat / K M 에 비례하게 된다. 여기서 1 / K M 은 효소와 기질이 결합하여 효소-기질 복합체를 만드는 정도와 효소-기질 복합체가 분해되지 않고 유지되는 정도를 합친 지표이고, k cat 은 효소-기질 복합체가 생성물을 만들어지는 평형 상수이므로 k cat / K M 은 기질과 효소로부터 얼마만큼의 생산물을 얻어낼 수 있는지에 대한 지표, 즉 효소의 촉매 효율을 나타내는 것이라 할 수 있다.
히알루로니다제의 산업적 이용 가능성은 효소 촉매 효율과 비례한다. 특히, 단클론 항체와 같은 고분자 약리 활성 물질과 함께 피하로 주사하는 경우에는 히알루로니다제의 효소 촉매 효율이 중요한 역할을 한다. 본 발명에 따른 변이체가 야생형 PH20보다 k cat / K M 이 높은 경우에는 고분자 약리 활성 물질에 포함된 히알루로니다제가 피하로 투여될 때, 피하 내에 존재하는 히알루론산을 더 빠르게 분해함으로 약리 활성 물질이 빨리 분산될 수 있게 하는 우월한 효과를 준다. 또한 본 발명에 따른 변이체가 야생형 PH20보다 k cat 이 큰 경우에는 동일한 효소 농도에서는 최대 반응 속도인 Vmax가 증가하여 동일한 시간에 더 많은 양의 히알루론산을 분해하게 되어 보다 넓은 범위에 약리 활성 물질을 분산시킬 수 있게 하는 우월한 효과를 준다.
따라서, 본 발명에 따른 PH20변이체의 효소학적 특성을 확인하기 위하여 각 변이체의 효소 반응 속도를 분석하고 이의 Vmax (최대 효소 반응 속도), Km (50% Vmax 조건에서 기질 농도), kcat (기질 전환율), kcat/Km (효소 촉매 효율) 결과를 실시예 4에서 비교하였다. 이 결과를 보면, 야생형 PH20 대비하여 본 발명에 따른 PH20 변이체의 우월성을 입증할 수 있다.
실시예
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 예시하기 위한 것으로서, 본 발명의 범위가 이들 실시예에 의해 제한되는 것으로 해석되지는 않는 것은 당업계에서 통상의 지식을 가진 자에게 있어서 자명할 것이다.
실시예 1. PH20 변이체 제작
PH20 변이체 제작을 위해 야생형 PH20의 cDNA (clone ID: hMU002604)를 한국인간유전자은행에서 구입하였다. 야생형 PH20은 아미노산 L36부터 S490까지를 암호화한다. 중합효소 연쇄반응(polymerase chain reaction, 이하 PCR이라고 함)을 이용하여 PH20의 유전자를 증폭하고 pcDNA3.4-TOPO vector의 Xho I과 Not I 제한효소 자리에 삽입하였다. ExpiCHO 세포에서의 발현을 위해 PH20의 고유한 신호 펩티드 대신 인간 성장호르몬, 인간 혈청 알부민, 또는 인간 Hyal1의 신호 펩티드 중 하나를 신호 펩티드로 사용하였다. HisTrap 컬럼을 이용한 단백질 정제를 위해 PH20 cDNA의 3'-말단에 His-tag의 DNA 서열이 위치하게 하였다. PH20 변이체의 아미노산 치환은 PCR 방법을 이용하였고, 아미노산의 치환 확인은 DNA sequencing을 이용하였다.
PH20 변이체의 클로닝에 사용한 프라이머의 목록은 표 4에 정리되어 있고, 이의 구체적 서열은 표 5에 정리되어 있다.
효소 활성과 열 안정성이 증가한 PH20 변이체를 찾은 후, His-tag이 없는 형태로도 PH20 변이체의 cDNA를 제작하였다.
PH20 변이체의 제작은 해당 PH20 변이체의 cDNA를 이용하여 다음과 같이 제작하였다.
변이체의 발현은 ExpiCHO 발현 시스템을 사용하였다. ExpiCHO 세포의 세포수가 6x106/mL이 되었을 때 야생형 또는 변이체 PH20의 cDNA가 pcDNA3.4-TOPO 벡터에 삽입된 플라스미드로 ExpiFectamine CHO Reagent를 이용하여 ExpiCHO 세포를 형질주입 시켰다. 세포배양액은 ExpiCHO Expression Medium (100~500 mL)을 이용하였다. 형질주입 후 ExpiCHO 세포를 총 6일간 130 rpm에서 진탕 배양하였으며, 이 기간 동안 37 ℃에서 1일 배양하고, 온도를 32 ℃로 낮추어서 5일간 더 배양하였다. 배양 완료 시 10,000 rpm에서 30분간 원심 분리하여 세포 상등액을 회수하였다.
ExpiCHO 세포에서 생산한 C-말단 His-tag이 붙은 야생형 및 변이체 PH20의 재조합단백질은 AKTA prime 장비(GE Healthcare사)를 이용하여 3단계의 컬럼 크로마토그래피로 정제하였는데, 변이체에 따라 HisTrap HP 컬럼, Q Sepharose 컬럼, Phenyl HP 컬럼 순서의 방법과 Q Sepharose 컬럼, HisTrap HP 컬럼, Butyl HP 컬럼의 3 단계로 정제하였다.
HisTrap HP 컬럼, Q Sepharose 컬럼, Phenyl HP 컬럼 순서의 정제는 다음과 같이 진행하였다. HisTrap HP 컬럼을 이용한 단백질 정제를 위해서 버퍼 A (20 mM sodium phosphate, pH 7.5, 0.5 M NaCl)와 버퍼 B (20 mM sodium phosphate, pH 7.5, 0.5 M NaCl, 0.5 M imidazole)을 제조하였다. 단백질을 HisTrap 컬럼에 결합시키고, 비특이적(non-specific)으로 결합한 단백질을 제거하기 위해 버퍼 A를 5 column volume (CV) 흘려주고, conductivity가 일정하게 유지되는 것을 확인한 후 20%의 버퍼 B를 5 CV 흘려 단백질을 용출하였다. 용출된 단백질을 Dialysis buffer (20 mM sodium phosphate, pH 7.5, 50 mM NaCl)를 이용하여 투석하였다. Q Sepharose 컬럼을 이용한 단백질 정제를 위해서 버퍼 A (20 mM sodium phosphate, pH 7.5)와 버퍼 B (20 mM sodium phosphate, pH 7.5, 0.5 M NaCl)를 제조하였다. 단백질을 Q Sepharose 컬럼에 결합시키고, 버퍼 A를 5 CV 흘려주어 비 특이적으로 결합한 단백질을 제거한 후, 0~100%의 농도 기울기로 버퍼 B를 5 CV 흘려주어 단백질을 용출하였다. Phenyl HP 컬럼을 이용한 단백질 정제를 위해 버퍼 A (20 mM sodium phosphate, pH 7.0, 1.5 M (NH4)2SO4)와 버퍼 B (20 mM sodium phosphate, pH 7.0)를 제조하였다. 단백질을 Phenyl 컬럼에 결합시키고, 버퍼 A를 5 CV 흘려주어 비특이적으로 결합한 단백질을 제거한 후, 0~100%의 농도 기울기로 버퍼 B를 5 CV 흘려주어 단백질을 용출하였다.
Q Sepharose 컬럼, HisTrap HP 컬럼, Butyl HP 컬럼 순서의 정제는 다음과 같이 진행하였다. Q Sepharose 컬럼을 이용한 단백질 정제를 위해서 버퍼 A (20 mM NaPi, 15 mM NaCl, pH 8.0)와 버퍼 B (20 mM NaPi, 500 mM NaCl, pH 8.0)를 각각 제조하였다. 배양액의 pH와 conductivity를 Buffer A와 동일하게 맞추고자 1 M Tris 버퍼를 이용하여 pH 8로 적정하였으며 purified water (PW)를 부어 conductivity를 5 mS/cm 이하로 맞추었다. 그리고 0.22 μm pore 크기의 membrane에 배양액을 여과하였다. 다음 Q Sepharose 컬럼에 단백질을 결합시킨 후 버퍼 A를 5 column volume (CV) 흘려주어 비특이적(non-specific)으로 결합한 단백질을 제거하였다. 타겟 단백질의 용출을 위해 Buffer B를 3 CV 순차적으로 흘려주었다. HisTrap HP 컬럼을 이용한 단백질 정제를 위해서 Buffer A (20 mM NaPi, 500 mM NaCl, pH 7.5)와 Buffer B (20 mM NaPi, 500 mM NaCl, 500 mM Imidazole, pH 7.5)를 각각 제조하였다. 단백질 시료를 HisTrap HP 컬럼에 결합시킨 후 비특이적으로 결합된 단백질을 제거하고자 7% Buffer B를 10 CV 흘려주었으며, 타겟 단백질의 용출을 위해 40% Buffer B를 3 CV 흘려주었다. Butyl HP 컬럼을 이용한 단백질 정제를 위해서 Buffer A (20 mM NaPi, 1.5 M Ammonium sulfate, pH 7.0)와 Buffer B (20 mM NaPi, pH 7.0)를 각각 제조하였다. 컬럼에 로딩하기 위해 3 M Ammonium sulfate 용액과 단백질 시료를 1:1 비율로 섞은 후 0.22 μm pore 크기의 membrane에 여과하였다. 단백질 시료를 Butyl HP 컬럼에 결합시킨 후 Buffer A를 5 CV 흘려 불순물을 제거하였다. 그리고 0~100% Buffer B 직선농도구배로 타겟 단백질을 용출하였으며, Dialysis buffer (20 mM NaPi, 100 mM NaCl, pH 7.0)를 이용하여 투석하였다. 본 발명에 따른 변이체에 대해 본문에 제시하는 방법으로 정제를 진행하였고, 각 정제 산물에 대해 10% SDS-PAGE 분석을 실시하여 도 1과 도 3에 제시하였다.
야생형과 변이체 PH20의 효소 활성은 turbidimetric assay를 이용하여 측정하였다.
Turbidimetric assay은 히알루론산과 알부민(BSA) 혼합 시 생성되는 침전을 흡광도를 이용하여 측정하는 방법으로, PH20에 의해 히알루론산이 가수분해되면 알부민과 혼합 시 흡광도가 감소한다. 일반적으로는 다음과 같이 진행하였다. 히알루로니다제 PH20 (Sigma)를 1, 2, 5, 7.5, 10, 15, 20, 30, 50, 60 unit/mL되게 희석하여 각 튜브에 준비한다. 정제된 단백질 샘플을 enzyme diluent buffer (20 mM Tris·HCl, pH 7.0, 77 mM NaCl, 0.01% (w/v) bovine serum albumin)에 용해하여 100X, 300X, 600X, 1200X, 2400X 되게 희석하여 각 튜브에 준비한다. 새로운 튜브에 3 mg/mL인 히알루론산 용액의 농도가 0.3 mg/mL 되게 10배 희석하여 각 튜브의 부피가 180 ㎕가 되게 한다. 희석한 히알루론산 용액에 효소를 60 ㎕ 넣고 혼합하여 37℃에서 45분간 반응시킨다. 반응이 끝나면 96-well plate에 반응시킨 효소 50 ㎕와 acidic albumin solution 250 ㎕를 각 well에 넣고 10분간 진탕한 후 600 nm에서 분광 광도계로 흡광도를 측정한다.
단백질의 열 안정성의 측정방법은 동적 광 산란기기 (Dynamic Light Scattering, DLS)을 이용한 응집온도 측정, Sypro-Orange dye를 이용하여 real-time PCR에서 측정한 melting temperature (Tm), 특정 온도에서 일정 시간 방치 후 효소 활성을 측정하는 방법 등의 방법이 있다. DLS를 이용한 응집온도 측정은 빛의 산란을 이용하여 분자의 응집 현상을 측정하기 때문에 민감도가 높으며 일반적으로 단백질의 녹는점(Tm)보다 온도가 낮다. 각 변이체를 0.2 mg/mL의 동일한 농도의 용액으로 제조한 후, 측정하기 때문에 이 결과값을 응집 온도로 사용하여 각 변이체의 물리적 특성을 비교할 수 있다 (Philo, J.S. (2009) Cur Pharm Biotech 10, 359-372).
서열번호 3의 PH20 변이체로부터 치환 또는 절단하여 본 발명에서 제작한 PH20변이체의 아미노산의 서열은 아래의 표 6과 같다.
본 발명에서는 표 6에 제시한 서열에서 C-말단에 단백질 정제를 위해서 6개의 Histidine을 추가한 변이체로 실험을 하였지만, 이러한 C-말단의 추가는 효소의 활성 및 단백질의 안정성에는 영향이 없음을 확인하였다. 본 발명에 따른 변이체는 HM과 일련번호의 조합으로 명명하였고, 실시예 3에 따른 변이체는 각각 Hyal2-변이체, Hyal3-변이체, Hyal4-변이체로 명명하였다.
실시예 2. 본 발명에 따른 PH20 변이체 특성 분석
서열번호 3의 아미노산 서열을 기반으로, N말단과 C말단의 절단을 포함한 변이체 연구를 통하여 단백질의 구조와 기능에 대한 추가 연구를 진행하였다. 제조된 변이체의 발현량과 활성 분석 결과, 응집온도는 표 7에 기재된 바와 같다.
발현량 (Expression Level)과 활성 분석 (Specific Activity)은 실시예 1에서 제시된 Turbidimetric Assay로 진행되었다. 이 Assay의 결과를 정리할 때, 배양액과 정제 후의 활성 분석을 각각의 정량 한도 (LOQ: Limit of Quantification)를 설정하여 배양액의 활성은 300 unit/mL을 초과할 때 “> LOQ”으로 표시하였고, 활성은 15 unit/μg을 초과할 때 “> LOQ”으로 표시하였다. 그 반대의 경우에는 부등호의 표시를 바꾸었다. 표 7에서는 이를 적용하여 각 발현량과 활성 분석의 정량 한도를 표시하고 이를 토대로 시험 결과를 정리하였다. 서열번호 1의 야생형 PH20 (L36-Y482)의 응집 온도는 46.5℃ 이며, 서열번호 3의 PH20 변이체 (F38-F468)의 응집 온도는 51℃이다.
상기 표 7에 기재된 바와 같이, 서열번호 3의 아미노산 서열을 갖는 변이체에있어서, 하나의 아미노산 잔기의 치환을 갖고 있는 변이체인 HM63, HM64, HM65, HM66, HM67, HM69, HM70, HM71, HM72, HM73, HM74, HM75, HM76, HM77, HM78, HM79, HM82, HM83, HM84, HM85, HM86, HM88, HM89, HM90, HM91, HM92, HM93, HM94, HM95, HM97, HM98, HM99, HM100, HM101, HM102, HM103, HM104, HM105, HM106, HM107, HM110, HM111, HM112, HM114, HM115, HM116, HM117, HM118, HM121, HM125, HM126, HM130, HM131, HM132, HM133, HM134, HM135, HM136, HM138, HM139, HM140, HM141, HM142, HM143, HM144, HM145, HM152, HM153, HM154, HM155, HM156, HM157, HM158, HM159, HM160, HM161, HM162, HM163, HM164, HM165, HM166, HM167, HM168, HM169, HM170, HM171, HM172, HM173, HM174, HM175, HM176, HM177, HM178, HM179, HM180, HM181, HM182, HM183, HM184, HM185, HM186, HM190, HM191, HM192, HM193, HM194, HM195, HM196, HM197, HM198, HM199, HM203, HM204, HM205, HM208, HM210, HM211, HM212, HM213, HM214, HM216, HM217, HM218, HM219, HM220, HM231, HM232, HM233, HM234, HM235, HM243, HM245, HM246 총 133종의 변이체는 정제 후 정제 분획에서의 활성도 유지되고 있으며, 응집 온도도 48 ℃ 내지 58 ℃의 범위를 갖는 열안정성이 높은 변이체임을 확인하였다. 이 중 HM63, HM64, HM65, HM66, HM67, HM69, HM70, HM71, HM72, HM73, HM74, HM75, HM76, HM77, HM78, HM79, HM82, HM83, HM84, HM85, HM86, HM88, HM89, HM90, HM91, HM92, HM93, HM94, HM95, HM98, HM99, HM100, HM101, HM102, HM103, HM104, HM105, HM106, HM107, HM110, HM111, HM112, HM114, HM115, HM116, HM117, HM118, HM121, HM125, HM126, HM130, HM131, HM132, HM133, HM134, HM135, HM136, HM138, HM139, HM140, HM141, HM142, HM143, HM144, HM145 총 65종의 변이체는 서열번호 3에서 PH20으로부터 치환된 치환 부위 중 하나의 위치를 변이한 변이체이며, 응집 온도는 48 ℃ 내지 58 ℃의 범위를 갖고 있다. HM97, HM152, HM153, HM154, HM155, HM156, HM157, HM158, HM159, HM160, HM161, HM162, HM163, HM164, HM165, HM166, HM167, HM168, HM169, HM170, HM171, HM172, HM173, HM174, HM175, HM176, HM177, HM178, HM179, HM180, HM181, HM182, HM183, HM184, HM185, HM186, HM190, HM191, HM192, HM193, HM194, HM195, HM196, HM197, HM198, HM199, HM203, HM204, HM205, HM208, HM210, HM211, HM212, HM213, HM214, HM216, HM217, HM218, HM219, HM220, HM231, HM232, HM233, HM234, HM235, HM243, HM245, HM246 총 68종의 변이체는 서열번호 3에서 PH20으로부터 치환된 치환 부위 이외의 부위 중 하나의 위치를 변이한 변이체이며, 응집 온도는 48 ℃ 내지 56 ℃의 범위를 갖고 있다.
이로써 서열번호 3으로부터 하나의 위치를 치환한 변이체는 어느 위치를 치환해도 서열번호 1의 야생형 PH20 (L36-Y482)의 응집 온도보다는 높은 값을 갖는 것을 알 수 있다. 단, 이 중 HM174, HM208, HM210, HM211은 배양액에서의 활성이 LOQ인 300 unit/mL 보다는 낮지만, 정제 후의 활성은 LOQ인 15 unit/μg 보다 높은 것이 발견되었다. 이러한 사례를 보면, 변이체의 활성을 배양액에서만 측정하게 되면, 변이체 자체만의 특성을 정확히 분석할 수는 없을 것으로 판단된다.
그리고, 서열번호 3의 아미노산 서열을 갖는 변이체에 있어, 상기 표 7에 기재된 것과 같이, HM146, HM147, HM149, HM262 및 HM263은 서열번호 3의 아미노산 서열을 갖는 변이체와 동일한 변이, 즉 아미노산 잔기의 치환을 유지하고 있지만, N-말단과 C-말단의 추가 절단을 포함한 것으로, 서열번호 3의 아미노산 서열을 갖는 변이체에 있어, 단백질의 발현과 활성에서 N-말단과 C-말단의 추가 절단에 의해 영향을 받지 않는다는 것을 확인할 수 있었다. 응집 온도도 서열번호 3과 크게 다르지 않은 49 ℃ 내지 53 ℃의 범위를 갖고 있으므로, 물리적 특성도 N-말단과 C-말단의 추가 절단에 의해 영향을 받지 않았음을 알 수 있었다.
또한, 서열번호 3의 아미노산 서열을 갖는 변이체에 있어, 상기 표 7에 기재된 것 중에서 하나 이상의 아미노산 치환 및 절단을 포함하고 있는 변이체인 HM96, HM150, HM254, HM261, HM266, HM268, HM271, HM275, HM276, HM279, HM280, HM287, 및 HM288 총 13종의 경우에도, 단백질의 발현이 성공적으로 이루어지고, 나아가 효소 활성도 유지하고 있음을 확인할 수 있었고, 응집 온도도 48 ℃ 내지 59 ℃의 범위를 갖고 있다. 따라서, 이러한 다중 치환의 경우에도 단백질의 활성과 물리적 특성을 유지하는 것을 확인할 수 있었다. 다만, 다중 치환의 경우에는 이를 구성하는 각 단일 치환에서 나타나는 특성의 조합만으로는 예측할 수 없는 효소 활성과 응집 온도를 갖는 것으로 나타났다.
실시예 3. Hyal2, Hyal3, Hyal4의 서열로 치환된 변이체의 활성 분석
서열번호 1의 야생형 PH20의 아미노산 서열에서 M345~I361 구간을 대신하여 Hyal1 이외에 인간에 존재하는 다른 종류의 히알루로니다제인 Hyal2 (TTSTETCQYLKDYLTRL)와 Hyal3 (SSSEEECWHLHDYLVDT), 그리고 Hyal4 (TASKANCTKVKQFVSSD)의 아미노산 서열을 상기 M345~I361 구간에 도입하여 단백질의 안정성이 어떻게 변화하는지를 알아보고자 하였다.
성숙된 야생형 PH20 (L36-S490)의 M345~I361 부위를 각각 Hyal2, Hyal3 및 Hyal4의 대응되는 서열로 치환된 변이체를 각각 Hyal2-변이체, Hyal3-변이체 및 Hyal4-변이체라고 한다.
Hyal2-변이체, Hyal3-변이체 그리고 Hyal4-변이체를 각각 제작한 후, 이들 변이체의 열 안정성을 분석하였다 (도 2, 참조). 그 결과 DLS로 측정한 Hyal3-변이체의 응집온도는 48℃로 46.5℃인 야생형 PH20보다 1.5℃ 높은 측정값을 나타내어 열 안정성이 증가한 것으로 판단된다.
또한, ExpiCHO 세포 배양액에서 이들 변이체의 발현 여부를 확인하고자 HisTrap 컬럼을 사용하여 동일한 방법으로 정제하고, SDS-PAGE 분석으로 단백질의 발현량을 비교한 결과, Hyal3-변이체의 발현량이 가장 많았고, Hyal2-변이체와 Hyal4-변이체 순으로 발현량이 많았다.
실시예 4. 본 발명에 따른 변이체의 열안정성 분석
본 발명에 따른 변이체의 열안정성을 확인하기 위하여 SDS-PAGE 분석을 실시하였다. 정제된 서열번호 1의 야생형 PH20(L36-Y482)과 본 발명에 따른 PH20 변이체 중 서열번호 3의 정제된 단백질(F38-F468)을 각각 42℃에서 7일 동안 보관한 다음 10% SDS-PAGE 분석을 환원조건과 비환원조건에서 실시하였다 (도 4).
그 결과, 야생형 PH20(L36-Y482)의 경우에는 응집물이 관찰되는데 (도 4 Lane G), 서열번호 3의 PH20변이체(F38-F468)의 경우에는 응집물이 관찰되지 않았다 (도 4 Lane H). 이는 두 단백질의 응집온도의 차이로 인하여 응집 현상의 차이가 발생하는 것으로 확인되었다. 이로써 본 발명에 따른 변이체의 높은 응집 온도로 인하여 야생형 PH20보다 높은 열안정성을 갖게 되어 더 넓은 산업적 이용이 가능할 것으로 판단된다.
실시예 5. 본 발명에 따른 변이체의 효소 반응 속도 (Enzyme kinetics) 분석
본 발명에 따른 변이체의 효소 반응 속도 (Enzyme kinetics)를 분석하기 위해 Morgan-Elson 방법 (Takahashi, T. et al (2003) Anal Biochem 322:257-263)으로 효소 활성을 측정하였다. Morgan-Elson 방법은 히알루론산이 히알루로니다제에 의해 가수분해되었을 때, 생성된 N-acetyl-D-glucosamine (GlcNAc)의 환원 말단과 Ehrlich’s Reagent인 para-dimetylaminobenzaldehyde (DMAB)의 반응에 의해 생성되는 붉은색 물질을 정량(545 nm)하는 비색분석법이다. N-acetyl-D-glucosamine (GlcNAc, Sigma)를 희석 완충 용액 (0.1 M NaPi, 0.1 M NaCl, 1.5 mM Saccharic Acid 1,4-lactone, pH 5.35)로 0.25, 0.50, 0.75, 1.00, 1.25 mM 되게 희석하여 준비한 각 시험관에 Tetraborate를 처리하여 환원 후, DMAB를 첨가하여 발색 반응시켰다. 반응 후 545 nm에서 흡광도를 측정하여 GlcNAc의 표준 반응 곡선을 작성하였다. 기질인 히알루론산을 희석 완충 용액으로 0.54, 0.65, 0.87, 1.23, 2.17 μM 되게 희석하여 준비한 각 시험관에 히알루로니다제를 첨가하여 37℃에서 5분간 반응시키고 100℃에서 5분간 가열하여 효소 반응을 종료시키고, Tetraborate를 처리하여 환원 후, DMAB를 첨가하여 발색 반응시켰다. 반응 후 545 nm에서 흡광도를 측정하여서 위의 GlcNAc의 표준 반응 곡선을 이용하여 효소 활성을 측정하였다. 이 방법을 사용하여 서열번호 1의 야생형 PH20 및 본 발명에 따른 PH20 변이체의 효소 반응 속도 (Enzyme kinetics)를 분석하면 Lineweaver-Burk 곡선의 직선성이 확인되어 본 발명에 따른 PH20 변이체는 Michaelis-Menten 효소 반응 속도 공식에 따르는 것을 확인하였다.
표 8은 서열번호 1의 야생형 PH20 (L36-Y482), 서열번호 3의 PH20 변이체 (F38-F468), HM261 및 HM268에 대한 효소 반응 속도 분석 결과인 Vmax (최대 효소 반응 속도), K m (50% Vmax 조건에서 기질 농도), k cat (기질 전환율), k cat/K m (효소 촉매 효율)을 제시하였다. K m 값이 작을수록 효소의 기질 결합력이 증가하고, k cat 값은 커질수록 효소의 기질 전환율이 증가하게 되므로 k cat/K m 은 각 PH20 변이체의 효소 촉매 효율이 야생형 PH20보다 증가하였음을 확인할 수 있었다. 또한, 서열번호 3, HM261 및 HM268은 k cat 값이 서열번호 1의 야생형 PH20보다 크므로 효소의 기질 전환율이 크기 때문에 야생형 PH20 대비 각 PH20 변이체의 산업적 이용 가능성이 더 크다는 것을 알 수 있었다.
전자파일 첨부하였음.
SEQUENCE LISTING
<110> Alteogen, Inc
<120> Novel Hyaluronidase Variants with Improved Stability and
Pharmaceutical Composition Comprising the Same
<130> PP-B2512
<150> KR 10-2020-0009046
<151> 2020-01-23
<160> 316
<170> PatentIn version 3.2
<210> 1
<211> 509
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 1
Met Gly Val Leu Lys Phe Lys His Ile Phe Phe Arg Ser Phe Val Lys
1 5 10 15
Ser Ser Gly Val Ser Gln Ile Val Phe Thr Phe Leu Leu Ile Pro Cys
20 25 30
Cys Leu Thr Leu Asn Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro
35 40 45
Phe Leu Trp Ala Trp Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe
50 55 60
Asp Glu Pro Leu Asp Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg
65 70 75 80
Ile Asn Ala Thr Gly Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu
85 90 95
Gly Tyr Tyr Pro Tyr Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly
100 105 110
Gly Ile Pro Gln Lys Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys
115 120 125
Lys Asp Ile Thr Phe Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val
130 135 140
Ile Asp Trp Glu Glu Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro
145 150 155 160
Lys Asp Val Tyr Lys Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn
165 170 175
Val Gln Leu Ser Leu Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe
180 185 190
Glu Lys Ala Gly Lys Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys
195 200 205
Leu Leu Arg Pro Asn His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys
210 215 220
Tyr Asn His His Tyr Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn
225 230 235 240
Val Glu Ile Lys Arg Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser
245 250 255
Thr Ala Leu Tyr Pro Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val
260 265 270
Ala Ala Thr Leu Tyr Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val
275 280 285
Ser Lys Ile Pro Asp Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr
290 295 300
Arg Ile Val Phe Thr Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu
305 310 315 320
Leu Val Tyr Thr Phe Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile
325 330 335
Val Ile Trp Gly Thr Leu Ser Ile Met Arg Ser Met Lys Ser Cys Leu
340 345 350
Leu Leu Asp Asn Tyr Met Glu Thr Ile Leu Asn Pro Tyr Ile Ile Asn
355 360 365
Val Thr Leu Ala Ala Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln
370 375 380
Gly Val Cys Ile Arg Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu
385 390 395 400
Asn Pro Asp Asn Phe Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr
405 410 415
Val Arg Gly Lys Pro Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys
420 425 430
Phe Tyr Cys Ser Cys Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp
435 440 445
Val Lys Asp Thr Asp Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys
450 455 460
Ile Asp Ala Phe Leu Lys Pro Pro Met Glu Thr Glu Glu Pro Gln Ile
465 470 475 480
Phe Tyr Asn Ala Ser Pro Ser Thr Leu Ser Ala Thr Met Phe Ile Val
485 490 495
Ser Ile Leu Phe Leu Ile Ile Ser Ser Val Ala Ser Leu
500 505
<210> 2
<211> 435
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 2
Met Ala Ala His Leu Leu Pro Ile Cys Ala Leu Phe Leu Thr Leu Leu
1 5 10 15
Asp Met Ala Gln Gly Phe Arg Gly Pro Leu Leu Pro Asn Arg Pro Phe
20 25 30
Thr Thr Val Trp Asn Ala Asn Thr Gln Trp Cys Leu Glu Arg His Gly
35 40 45
Val Asp Val Asp Val Ser Val Phe Asp Val Val Ala Asn Pro Gly Gln
50 55 60
Thr Phe Arg Gly Pro Asp Met Thr Ile Phe Tyr Ser Ser Gln Leu Gly
65 70 75 80
Thr Tyr Pro Tyr Tyr Thr Pro Thr Gly Glu Pro Val Phe Gly Gly Leu
85 90 95
Pro Gln Asn Ala Ser Leu Ile Ala His Leu Ala Arg Thr Phe Gln Asp
100 105 110
Ile Leu Ala Ala Ile Pro Ala Pro Asp Phe Ser Gly Leu Ala Val Ile
115 120 125
Asp Trp Glu Ala Trp Arg Pro Arg Trp Ala Phe Asn Trp Asp Thr Lys
130 135 140
Asp Ile Tyr Arg Gln Arg Ser Arg Ala Leu Val Gln Ala Gln His Pro
145 150 155 160
Asp Trp Pro Ala Pro Gln Val Glu Ala Val Ala Gln Asp Gln Phe Gln
165 170 175
Gly Ala Ala Arg Ala Trp Met Ala Gly Thr Leu Gln Leu Gly Arg Ala
180 185 190
Leu Arg Pro Arg Gly Leu Trp Gly Phe Tyr Gly Phe Pro Asp Cys Tyr
195 200 205
Asn Tyr Asp Phe Leu Ser Pro Asn Tyr Thr Gly Gln Cys Pro Ser Gly
210 215 220
Ile Arg Ala Gln Asn Asp Gln Leu Gly Trp Leu Trp Gly Gln Ser Arg
225 230 235 240
Ala Leu Tyr Pro Ser Ile Tyr Met Pro Ala Val Leu Glu Gly Thr Gly
245 250 255
Lys Ser Gln Met Tyr Val Gln His Arg Val Ala Glu Ala Phe Arg Val
260 265 270
Ala Val Ala Ala Gly Asp Pro Asn Leu Pro Val Leu Pro Tyr Val Gln
275 280 285
Ile Phe Tyr Asp Thr Thr Asn His Phe Leu Pro Leu Asp Glu Leu Glu
290 295 300
His Ser Leu Gly Glu Ser Ala Ala Gln Gly Ala Ala Gly Val Val Leu
305 310 315 320
Trp Val Ser Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile
325 330 335
Lys Glu Tyr Met Asp Thr Thr Leu Gly Pro Phe Ile Leu Asn Val Thr
340 345 350
Ser Gly Ala Leu Leu Cys Ser Gln Ala Leu Cys Ser Gly His Gly Arg
355 360 365
Cys Val Arg Arg Thr Ser His Pro Lys Ala Leu Leu Leu Leu Asn Pro
370 375 380
Ala Ser Phe Ser Ile Gln Leu Thr Pro Gly Gly Gly Pro Leu Ser Leu
385 390 395 400
Arg Gly Ala Leu Ser Leu Glu Asp Gln Ala Gln Met Ala Val Glu Phe
405 410 415
Lys Cys Arg Cys Tyr Pro Gly Trp Gln Ala Pro Trp Cys Glu Arg Lys
420 425 430
Ser Met Trp
435
<210> 3
<211> 509
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 3
Met Gly Val Leu Lys Phe Lys His Ile Phe Phe Arg Ser Phe Val Lys
1 5 10 15
Ser Ser Gly Val Ser Gln Ile Val Phe Thr Phe Leu Leu Ile Pro Cys
20 25 30
Cys Leu Thr Leu Asn Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro
35 40 45
Phe Leu Trp Ala Trp Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe
50 55 60
Asp Glu Pro Leu Asp Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg
65 70 75 80
Ile Asn Ala Thr Gly Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu
85 90 95
Gly Tyr Tyr Pro Tyr Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly
100 105 110
Gly Ile Pro Gln Lys Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys
115 120 125
Lys Asp Ile Thr Phe Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val
130 135 140
Ile Asp Trp Glu Glu Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro
145 150 155 160
Lys Asp Val Tyr Lys Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn
165 170 175
Val Gln Leu Ser Leu Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe
180 185 190
Glu Lys Ala Gly Lys Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys
195 200 205
Leu Leu Arg Pro Asn His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys
210 215 220
Tyr Asn His His Tyr Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn
225 230 235 240
Val Glu Ile Lys Arg Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser
245 250 255
Thr Ala Leu Tyr Pro Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val
260 265 270
Ala Ala Thr Leu Tyr Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val
275 280 285
Ser Lys Ile Pro Asp Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr
290 295 300
Arg Ile Val Phe Thr Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu
305 310 315 320
Leu Val Tyr Thr Phe Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile
325 330 335
Val Ile Trp Gly Ser Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln
340 345 350
Ala Ile Lys Glu Tyr Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn
355 360 365
Val Thr Leu Ala Ala Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln
370 375 380
Gly Val Cys Ile Arg Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu
385 390 395 400
Asn Pro Asp Asn Phe Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr
405 410 415
Val Arg Gly Lys Pro Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys
420 425 430
Phe Tyr Cys Ser Cys Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp
435 440 445
Val Lys Asp Thr Asp Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys
450 455 460
Ile Asp Ala Phe Leu Lys Pro Pro Met Glu Thr Glu Glu Pro Gln Ile
465 470 475 480
Phe Tyr Asn Ala Ser Pro Ser Thr Leu Ser Ala Thr Met Phe Ile Val
485 490 495
Ser Ile Leu Phe Leu Ile Ile Ser Ser Val Ala Ser Leu
500 505
<210> 4
<211> 26
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 4
Met Ala Thr Gly Ser Arg Thr Ser Leu Leu Leu Ala Phe Gly Leu Leu
1 5 10 15
Cys Leu Pro Trp Leu Gln Glu Gly Ser Ala
20 25
<210> 5
<211> 18
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 5
Met Lys Trp Val Thr Phe Ile Ser Leu Leu Phe Leu Phe Ser Ser Ala
1 5 10 15
Tyr Ser
<210> 6
<211> 21
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 6
Met Ala Ala His Leu Leu Pro Ile Cys Ala Leu Phe Leu Thr Leu Leu
1 5 10 15
Asp Met Ala Gln Gly
20
<210> 7
<211> 93
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 7
atatggggaa ccctcagtat aactacaagc actgagacct gccaatatct gaaggattac 60
ctgaccagac tgctgaatcc ttacataatc aac 93
<210> 8
<211> 93
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 8
atatggggaa ccctcagtat atccagcagt gaggaagaat gctggcattt gcacgattac 60
ctggtagaca cactgaatcc ttacataatc aac 93
<210> 9
<211> 93
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 9
atatggggaa ccctcagtat aaccgcatct aaggcaaact gcacaaaagt aaaacaattc 60
gtctccagtg atctgaatcc ttacataatc aac 93
<210> 10
<211> 33
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 10
gaatatctcg aggccaccat gaagtgggtt aca 33
<210> 11
<211> 55
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 11
ctaattgcgg ccgctcatta gtggtgatgg tgatgatgga agaaaccaat tctgc 55
<210> 12
<211> 44
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 12
aattaggcgg ccgcctatta aaaggcgtcg atgcacacgc catc 44
<210> 13
<211> 64
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 13
ctctaattgc ggccgctcat tagtggtgat ggtgatgatg aaaggcgtcg atgcacacgc 60
catc 64
<210> 14
<211> 44
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 14
aattagagct cgaggccacc atgaaatggg tgacctttat ctcc 44
<210> 15
<211> 28
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 15
cagattctcg aggccaccat gaaatggg 28
<210> 16
<211> 51
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 16
atctggggct cctgggagaa caccaggcag aaggagagct gccaggccat c 51
<210> 17
<211> 54
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 17
atctggggct cctgggagaa caccaggacc caggagagct gccaggccat caag 54
<210> 18
<211> 44
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 18
agaacaccag gaccaaggag caatgccagg ccatcaagga gtac 44
<210> 19
<211> 44
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 19
aggagagctg ccaggccatc caggagtaca tggacacaac cctg 44
<210> 20
<211> 51
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 20
agctgccagg ccatcaagga gtacgtggac acaaccctga acccttatat c 51
<210> 21
<211> 42
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 21
aggagtacat ggacacaacc gcgaaccctt atatcatcaa tg 42
<210> 22
<211> 44
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 22
atcgtgatct ggggctcctg ggtgaacacc aggaccaagg agag 44
<210> 23
<211> 41
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 23
atctggggct cctgggagtt caccaggacc aaggagagct g 41
<210> 24
<211> 51
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 24
agctgccagg ccatcaagga gtacatgaaa acaaccctga acccttatat c 51
<210> 25
<211> 42
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 25
atcaaggagt acatggacta caccctgaac ccttatatca tc 42
<210> 26
<211> 42
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 26
atcaaggagt acatggacac aatgctgaac ccttatatca tc 42
<210> 27
<211> 43
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 27
accaggacca aggagagctg cgaggccatc aaggagtaca tgg 43
<210> 28
<211> 43
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 28
agtacatgga cacaaccctg atgccttata tcatcaatgt gac 43
<210> 29
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 29
tagaagattg tcacgccctg gccgttggca ttgatccgag gagagc 46
<210> 30
<211> 45
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 30
tgcaccagct cgatggaccg tttcttatac acgtccttag gcttc 45
<210> 31
<211> 45
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 31
accaaggaga gctgccaggc cgaaaaggag tacatggaca caacc 45
<210> 32
<211> 45
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 32
accaaggaga gctgccaggc ccaaaaggag tacatggaca caacc 45
<210> 33
<211> 45
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 33
accaaggaga gctgccaggc ctctaaggag tacatggaca caacc 45
<210> 34
<211> 45
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 34
accaaggaga gctgccaggc cgtcaaggag tacatggaca caacc 45
<210> 35
<211> 45
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 35
accaaggaga gctgccaggc cgcgaaggag tacatggaca caacc 45
<210> 36
<211> 45
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 36
accaaggaga gctgccaggc caacaaggag tacatggaca caacc 45
<210> 37
<211> 45
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 37
accaaggaga gctgccaggc caccaaggag tacatggaca caacc 45
<210> 38
<211> 48
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 38
aaggagagct gccaggccat caagatgtac atggacacaa ccctgaac 48
<210> 39
<211> 48
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 39
aaggagagct gccaggccat caagttctac atggacacaa ccctgaac 48
<210> 40
<211> 48
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 40
aaggagagct gccaggccat caagatatac atggacacaa ccctgaac 48
<210> 41
<211> 48
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 41
aaggagagct gccaggccat caagttgtac atggacacaa ccctgaac 48
<210> 42
<211> 48
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 42
aaggagagct gccaggccat caagcagtac atggacacaa ccctgaac 48
<210> 43
<211> 48
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 43
aaggagagct gccaggccat caaggtatac atggacacaa ccctgaac 48
<210> 44
<211> 96
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 44
atcgtgatct ggggctcctg ggtgaacacc aggaccaagg agagctgcca ggccatcaag 60
gagtacatgg acacaatgct gaacccttat atcatc 96
<210> 45
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 45
agctagcggc atcgtgatct ggcaatcctg ggagaacacc aggacc 46
<210> 46
<211> 45
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 46
agcggcatcg tgatctgggg ccactgggag aacaccagga ccaag 45
<210> 47
<211> 48
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 47
agcggcatcg tgatctgggg ctccattgag aacaccagga ccaaggag 48
<210> 48
<211> 44
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 48
atcgtgatct ggggctcctg gtataacacc aggaccaagg agag 44
<210> 49
<211> 49
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 49
atcgtgatct ggggctcctg ggagaacgaa aggaccaagg agagctgcc 49
<210> 50
<211> 47
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 50
atctggggct cctgggagaa caccttcacc aaggagagct gccaggc 47
<210> 51
<211> 51
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 51
atctggggct cctgggagaa caccagggaa aaggagagct gccaggccat c 51
<210> 52
<211> 55
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 52
atctggggct cctgggagaa caccaggacc aagttgagct gccaggccat caagg 55
<210> 53
<211> 41
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 53
agaacaccag gaccaaggag atctgccagg ccatcaagga g 41
<210> 54
<211> 45
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 54
accaggacca aggagagctg cggggccatc aaggagtaca tggac 45
<210> 55
<211> 44
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 55
accaaggaga gctgccaggc cagaaaggag tacatggaca caac 44
<210> 56
<211> 51
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 56
agctgccagg ccatcaagga gtaccgggac acaaccctga acccttatat c 51
<210> 57
<211> 44
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 57
aggccatcaa ggagtacatg gtcacaaccc tgaaccctta tatc 44
<210> 58
<211> 47
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 58
aggccatcaa ggagtacatg gacagaaccc tgaaccctta tatcatc 47
<210> 59
<211> 45
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 59
atctggggct cctgggagaa caagaggacc aaggagagct gccag 45
<210> 60
<211> 47
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 60
atctggggct cctgggagaa caccctgacc aaggagagct gccaggc 47
<210> 61
<211> 51
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 61
atctggggct cctgggagaa caccagggtc aaggagagct gccaggccat c 51
<210> 62
<211> 57
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 62
atctggggct cctgggagaa caccaggacc aagtggagct gccaggccat caaggag 57
<210> 63
<211> 44
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 63
accaaggaga gctgccaggc ctggaaggag tacatggaca caac 44
<210> 64
<211> 44
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 64
aggccatcaa ggagtacatg tacacaaccc tgaaccctta tatc 44
<210> 65
<211> 51
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 65
atctggggct cctgggagaa caccaggtgg aaggagagct gccaggccat c 51
<210> 66
<211> 44
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 66
agctgccagg ccatcaagga gtggatggac acaaccctga accc 44
<210> 67
<211> 48
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 67
agcggcatcg tgatctgggg ctccgacgag aacaccagga ccaaggag 48
<210> 68
<211> 45
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 68
atcgtgatct ggggctcctg gcagaacacc aggaccaagg agagc 45
<210> 69
<211> 51
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 69
atctggggct cctgggagaa caccaggcac aaggagagct gccaggccat c 51
<210> 70
<211> 54
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 70
atctggggct cctgggagaa caccaggacc ttcgagagct gccaggccat caag 54
<210> 71
<211> 44
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 71
agaacaccag gaccaaggag gactgccagg ccatcaagga gtac 44
<210> 72
<211> 47
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 72
accaggacca aggagagctg ctacgccatc aaggagtaca tggacac 47
<210> 73
<211> 44
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 73
aggaccaagg agagctgcca ggaaatcaag gagtacatgg acac 44
<210> 74
<211> 51
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 74
agctgccagg ccatcaagga gtactacgac acaaccctga acccttatat c 51
<210> 75
<211> 44
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 75
aggccatcaa ggagtacatg cagacaaccc tgaaccctta tatc 44
<210> 76
<211> 47
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 76
aggccatcaa ggagtacatg gacctaaccc tgaaccctta tatcatc 47
<210> 77
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 77
atcaaggagt acatggacac agagctgaac ccttatatca tcaatg 46
<210> 78
<211> 43
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 78
agtacatgga cacaaccctg gagccttata tcatcaatgt gac 43
<210> 79
<211> 48
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 79
agcggcatcg tgatctgggg ctcccatgag aacaccagga ccaaggag 48
<210> 80
<211> 54
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 80
atctggggct cctgggagaa caccaggacc gacgagagct gccaggccat caag 54
<210> 81
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 81
atcaaggagt acatggacac acacctgaac ccttatatca tcaatg 46
<210> 82
<211> 44
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 82
tttggaatca caggaggagc ccgagagtat gcggagctaa acag 44
<210> 83
<211> 41
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 83
tttggaatca caggaggagc agagtatgcg gagctaaaca g 41
<210> 84
<211> 62
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 84
ctctaattgc ggccgcctat tagtggtgat ggtgatgatg gtccacggca tctgtgtcct 60
tc 62
<210> 85
<211> 74
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 85
agaacaccag gaccaaggag cagtgccagg ccatcaagga gtacatggac cgaaccctga 60
acccttatat catc 74
<210> 86
<211> 55
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 86
taaaagagaa caggctcata tccaggggct cggcaaactt gcccaggcag aactc 55
<210> 87
<211> 53
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 87
taaaagagaa caggctcata tccaggggcg cgtcaaactt gcccaggcag aac 53
<210> 88
<211> 48
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 88
taaaagagaa caggctcata tccagggcct cgtcaaactt gcccaggc 48
<210> 89
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 89
taaaagagaa caggctcata tccgcgggct cgtcaaactt gcccag 46
<210> 90
<211> 42
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 90
accaggatcg tgtttacaga cgcggtgctg aagttcctgt cc 42
<210> 91
<211> 42
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 91
aggatcgtgt ttacagacca ggcgctgaag ttcctgtccc ag 42
<210> 92
<211> 42
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 92
atcgtgttta cagaccaggt ggcgaagttc ctgtcccagg at 42
<210> 93
<211> 45
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 93
atcgtgttta cagaccaggt gctggcgttc ctgtcccagg atgag 45
<210> 94
<211> 47
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 94
gccctgtacc ctagcatcta tctggccacc cagcagagcc cagtggc 47
<210> 95
<211> 50
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 95
ctgtacccta gcatctatct gaacgcccag cagagcccag tggccgctac 50
<210> 96
<211> 51
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 96
taccctagca tctatctgaa caccgcgcag agcccagtgg ccgctacact g 51
<210> 97
<211> 55
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 97
taccctagca tctatctgaa cacccaggcg agcccagtgg ccgctacact gtatg 55
<210> 98
<211> 54
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 98
agcatctatc tgaacaccca gcagagcgca gtggccgcta cactgtatgt gagg 54
<210> 99
<211> 48
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 99
tatctgaaca cccagcagag cccagcggcc gctacactgt atgtgagg 48
<210> 100
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 100
tgtcactccg gtgatagaat cggcatatgg atagtagccc agtctg 46
<210> 101
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 101
tcactgtcac tccggtgata gaagcgatat atggatagta gcccag 46
<210> 102
<211> 51
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 102
tccgttcact gtcactccgg tgatagcatc gatatatgga tagtagccca g 51
<210> 103
<211> 47
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 103
tccgttcact gtcactccgg tggcagaatc gatatatgga tagtagc 47
<210> 104
<211> 44
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 104
ttgtccactg gcatgtagaa ggcgatgtcc ttcttagcct tatc 44
<210> 105
<211> 52
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 105
tgcccagatt gtccactggc atgtaggcgg tgatgtcctt cttagcctta tc 52
<210> 106
<211> 45
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 106
tgcccagatt gtccactggc atggcgaagg tgatgtcctt cttag 45
<210> 107
<211> 50
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 107
agatcgtcgt tcctcttgat ctccgcattg aaacaggagc cgttgtagcc 50
<210> 108
<211> 53
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 108
gacagatcgt cgttcctctt gatcgccaca ttgaaacagg agccgttgta gcc 53
<210> 109
<211> 54
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 109
agccaagaca gatcgtcgtt cctcttggcc tccacattga aacaggagcc gttg 54
<210> 110
<211> 51
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 110
agccaagaca gatcgtcgtt cctcgcgatc tccacattga aacaggagcc g 51
<210> 111
<211> 44
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 111
tctgtggcct cggtcaggct cgcctgcacg ttctgctgct gcac 44
<210> 112
<211> 44
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 112
ttctctgtgg cctcggtcag ggccagctgc acgttctgct gctg 44
<210> 113
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 113
tagccttctc tgtggcctcg gtcgcgctca gctgcacgtt ctgctg 46
<210> 114
<211> 44
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 114
ttagccttct ctgtggcctc ggccaggctc agctgcacgt tctg 44
<210> 115
<211> 47
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 115
tcgaactcct gcttagcctt ctctgcggcc tcggtcaggc tcagctg 47
<210> 116
<211> 44
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 116
tcgaactcct gcttagcctt cgctgtggcc tcggtcaggc tcag 44
<210> 117
<211> 43
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 117
ttctcgaact cctgcttagc cgcctctgtg gcctcggtca ggc 43
<210> 118
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 118
agagaggcta tccgcgtgtc tgcgatcccc gacgccaagt ccccac 46
<210> 119
<211> 44
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 119
aggctatccg cgtgtctaag gcccccgacg ccaagtcccc actg 44
<210> 120
<211> 47
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 120
aggctatccg cgtgtctaag atcgccgacg ccaagtcccc actgccc 47
<210> 121
<211> 51
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 121
agttttactg ctcttgttat tccaccgcga gctgtaagga gaaggctgat g 51
<210> 122
<211> 47
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 122
actgctcttg ttattccacc ctggcctgta aggagaaggc tgatgtg 47
<210> 123
<211> 45
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 123
aaggagaagg ctgatgtgaa ggccacagat gccgtggacg tgtgc 45
<210> 124
<211> 48
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 124
aaggagaagg ctgatgtgaa ggacgcagat gccgtggacg tgtgcatc 48
<210> 125
<211> 43
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 125
aaggctgatg tgaaggacac agctgccgtg gacgtgtgca tcg 43
<210> 126
<211> 81
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 126
atattcgcgg ccgcctatta gtggtgatgg tgatgatgaa aggcgtcgat gcacacgcca 60
gcagcgatgc acacgtccac g 81
<210> 127
<211> 80
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 127
atattcgcgg ccgcctatta gtggtgatgg tgatgatgaa aggcgtcgat gcacacggca 60
tcagcgatgc acacgtccac 80
<210> 128
<211> 75
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 128
atattcgcgg ccgcctatta gtggtgatgg tgatgatgaa aggcgtcgat gcacgcgcca 60
tcagcgatgc acacg 75
<210> 129
<211> 47
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 129
tgtcacgccc tggccggtgg cagcgatccg aggagagccg ataaaag 47
<210> 130
<211> 45
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 130
tgcaccagct cgatggaccg agccttatac acgtccttag gcttc 45
<210> 131
<211> 44
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 131
ttcactgtca ctccggtgat attatcgata tatggatagt agcc 44
<210> 132
<211> 47
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 132
tccgttcact gtcactccgg tctgagaatc gatatatgga tagtagc 47
<210> 133
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 133
accctagcat ctatctgaac accgatcaga gcccagtggc cgctac 46
<210> 134
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 134
accctagcat ctatctgaac accatccaga gcccagtggc cgctac 46
<210> 135
<211> 42
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 135
aggctatccg cgtgtctaag ggccccgacg ccaagtcccc ac 42
<210> 136
<211> 40
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 136
atccgcgtgt ctaagatcga cgacgccaag tccccactgc 40
<210> 137
<211> 40
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 137
agaaggctga tgtgaaggac gacgatgccg tggacgtgtg 40
<210> 138
<211> 40
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 138
agaaggctga tgtgaaggac cacgatgccg tggacgtgtg 40
<210> 139
<211> 40
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 139
agaaggctga tgtgaaggac aaagatgccg tggacgtgtg 40
<210> 140
<211> 40
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 140
agaaggctga tgtgaaggac ggagatgccg tggacgtgtg 40
<210> 141
<211> 40
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 141
agaaggctga tgtgaaggac ccagatgccg tggacgtgtg 40
<210> 142
<211> 40
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 142
agaaggctga tgtgaaggac atggatgccg tggacgtgtg 40
<210> 143
<211> 40
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 143
agaaggctga tgtgaaggac ttcgatgccg tggacgtgtg 40
<210> 144
<211> 82
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 144
ctctaattgc ggccgcctat tagtggtgat ggtgatgatg aaaggcgtcg atgcacacgc 60
ccctagcgat gcacacgtcc ac 82
<210> 145
<211> 76
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 145
ctctaattgc ggccgctcat tagtggtgat ggtgatgatg aaaggcgtcg atgcagtagc 60
catcagcgat gcacac 76
<210> 146
<211> 44
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 146
ttctctgtgg cctcggtcag ggtcagctgc acgttctgct gctg 44
<210> 147
<211> 41
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 147
aggagaaggc tgatgtgaag agcacagatg ccgtggacgt g 41
<210> 148
<211> 45
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 148
atcgtgttta cagaccaggt gccgaagttc ctgtcccagg atgag 45
<210> 149
<211> 45
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 149
atcgtgttta cagaccaggt gatgaagttc ctgtcccagg atgag 45
<210> 150
<211> 44
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 150
tctgtggcct cggtcaggct cgactgcacg ttctgctgct gcac 44
<210> 151
<211> 44
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 151
tctgtggcct cggtcaggct aatctgcacg ttctgctgct gcac 44
<210> 152
<211> 44
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 152
tctgtggcct cggtcaggct aaactgcacg ttctgctgct gcac 44
<210> 153
<211> 84
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 153
atcgtgatct ggggctcctg ggagttcacc aggacccagg agagctgcca ggccatccag 60
gagtacatgg acacaaccct gaac 84
<210> 154
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 154
accctagcat ctatctgaac accaaccaga gcccagtggc cgctac 46
<210> 155
<211> 17
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 155
gcccaggcag aactcgc 17
<210> 156
<211> 62
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 156
tctcgaactc ctgcttagcc ttatctgtgg cctcggtcat gctcagctgc acgttctgct 60
gc 62
<210> 157
<211> 46
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 157
accctagcat ctatctgaac accgcgcaga gcccagtggc cgctac 46
<210> 158
<211> 60
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 158
atcgtgatct ggggctcctg ggagatcacc aggaccatgg agagctgcca ggccatcaag 60
<210> 159
<211> 60
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 159
agcggcatcg tgatctgggg cgacctgtcg atctcctcga ccatggagag ctgccaggcc 60
<210> 160
<211> 57
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 160
agcggcatcg tgatctgggg cgacctgtcg atctccagga ccatggagag ctgccag 57
<210> 161
<211> 54
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 161
atctggggct cctgggagaa caccaggacc atggagagct gccaggccat caag 54
<210> 162
<211> 60
<212> DNA
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 162
atcgtgatct ggggctcctg ggagatcacc aggaccatgg agagctgcca ggccatcaag 60
<210> 163
<211> 455
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 163
Leu Asn Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp
1 5 10 15
Ala Trp Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro
20 25 30
Leu Asp Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala
35 40 45
Thr Gly Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr
50 55 60
Pro Tyr Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro
65 70 75 80
Gln Lys Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile
85 90 95
Thr Phe Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp
100 105 110
Glu Glu Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val
115 120 125
Tyr Lys Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu
130 135 140
Ser Leu Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala
145 150 155 160
Gly Lys Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg
165 170 175
Pro Asn His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His
180 185 190
His Tyr Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile
195 200 205
Lys Arg Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu
210 215 220
Tyr Pro Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr
225 230 235 240
Leu Tyr Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile
245 250 255
Pro Asp Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val
260 265 270
Phe Thr Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr
275 280 285
Thr Phe Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp
290 295 300
Gly Thr Leu Ser Ile Thr Thr Ser Thr Glu Thr Cys Gln Tyr Leu Lys
305 310 315 320
Asp Tyr Leu Thr Arg Leu Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu
325 330 335
Ala Ala Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys
340 345 350
Ile Arg Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp
355 360 365
Asn Phe Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly
370 375 380
Lys Pro Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys
385 390 395 400
Ser Cys Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp
405 410 415
Thr Asp Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala
420 425 430
Phe Leu Lys Pro Pro Met Glu Thr Glu Glu Pro Gln Ile Phe Tyr Asn
435 440 445
Ala Ser Pro Ser Thr Leu Ser
450 455
<210> 164
<211> 455
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 164
Leu Asn Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp
1 5 10 15
Ala Trp Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro
20 25 30
Leu Asp Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala
35 40 45
Thr Gly Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr
50 55 60
Pro Tyr Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro
65 70 75 80
Gln Lys Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile
85 90 95
Thr Phe Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp
100 105 110
Glu Glu Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val
115 120 125
Tyr Lys Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu
130 135 140
Ser Leu Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala
145 150 155 160
Gly Lys Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg
165 170 175
Pro Asn His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His
180 185 190
His Tyr Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile
195 200 205
Lys Arg Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu
210 215 220
Tyr Pro Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr
225 230 235 240
Leu Tyr Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile
245 250 255
Pro Asp Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val
260 265 270
Phe Thr Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr
275 280 285
Thr Phe Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp
290 295 300
Gly Thr Leu Ser Ile Ser Ser Ser Glu Glu Glu Cys Trp His Leu His
305 310 315 320
Asp Tyr Leu Val Asp Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu
325 330 335
Ala Ala Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys
340 345 350
Ile Arg Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp
355 360 365
Asn Phe Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly
370 375 380
Lys Pro Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys
385 390 395 400
Ser Cys Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp
405 410 415
Thr Asp Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala
420 425 430
Phe Leu Lys Pro Pro Met Glu Thr Glu Glu Pro Gln Ile Phe Tyr Asn
435 440 445
Ala Ser Pro Ser Thr Leu Ser
450 455
<210> 165
<211> 455
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 165
Leu Asn Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp
1 5 10 15
Ala Trp Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro
20 25 30
Leu Asp Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala
35 40 45
Thr Gly Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr
50 55 60
Pro Tyr Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro
65 70 75 80
Gln Lys Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile
85 90 95
Thr Phe Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp
100 105 110
Glu Glu Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val
115 120 125
Tyr Lys Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu
130 135 140
Ser Leu Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala
145 150 155 160
Gly Lys Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg
165 170 175
Pro Asn His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His
180 185 190
His Tyr Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile
195 200 205
Lys Arg Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu
210 215 220
Tyr Pro Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr
225 230 235 240
Leu Tyr Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile
245 250 255
Pro Asp Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val
260 265 270
Phe Thr Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr
275 280 285
Thr Phe Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp
290 295 300
Gly Thr Leu Ser Ile Thr Ala Ser Lys Ala Asn Cys Thr Lys Val Lys
305 310 315 320
Gln Phe Val Ser Ser Asp Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu
325 330 335
Ala Ala Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys
340 345 350
Ile Arg Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp
355 360 365
Asn Phe Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly
370 375 380
Lys Pro Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys
385 390 395 400
Ser Cys Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp
405 410 415
Thr Asp Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala
420 425 430
Phe Leu Lys Pro Pro Met Glu Thr Glu Glu Pro Gln Ile Phe Tyr Asn
435 440 445
Ala Ser Pro Ser Thr Leu Ser
450 455
<210> 166
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 166
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Met Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 167
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 167
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Gln Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 168
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 168
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Gln Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 169
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 169
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Gln Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 170
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 170
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Gln Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 171
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 171
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Val Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 172
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 172
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Ala Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 173
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 173
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Val Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 174
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 174
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Phe Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 175
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 175
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Lys Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 176
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 176
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Tyr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 177
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 177
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Met Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 178
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 178
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Glu Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 179
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 179
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Met Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 180
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 180
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Asn Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 181
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 181
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Lys Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 182
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 182
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Glu Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 183
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 183
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Gln Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 184
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 184
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ser Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 185
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 185
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Val Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 186
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 186
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ala Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 187
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 187
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Asn Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 188
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 188
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Thr Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 189
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 189
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Met Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 190
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 190
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Phe Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 191
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 191
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Ile Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 192
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 192
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Leu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 193
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 193
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Gln Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 194
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 194
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Val Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 195
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 195
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Lys Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Val Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Met Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 196
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 196
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gln Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 197
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 197
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly His
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 198
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 198
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Ile Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 199
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 199
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Tyr Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 200
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 200
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Glu Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 201
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 201
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Phe Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 202
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 202
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Glu Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 203
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 203
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Leu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 204
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 204
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ile Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 205
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 205
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gly Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 206
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 206
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Arg Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 207
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 207
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Arg Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 208
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 208
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Val Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 209
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 209
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Arg Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 210
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 210
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Lys Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 211
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 211
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Leu Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 212
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 212
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Val Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 213
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 213
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Trp Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 214
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 214
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Trp Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 215
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 215
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Tyr Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 216
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 216
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Trp Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 217
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 217
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Trp
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 218
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 218
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Asp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 219
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 219
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Gln Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 220
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 220
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg His Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 221
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 221
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Phe Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 222
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 222
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Asp Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 223
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 223
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Tyr Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 224
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 224
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Glu Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 225
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 225
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Tyr Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 226
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 226
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Gln Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 227
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 227
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Leu Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 228
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 228
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Glu Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 229
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 229
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Glu Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 230
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 230
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
His Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 231
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 231
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Asp Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 232
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 232
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr His Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 233
<211> 430
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 233
Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp Asn
1 5 10 15
Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp Met
20 25 30
Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly Gln
35 40 45
Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr Ile
50 55 60
Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys Ile
65 70 75 80
Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe Tyr
85 90 95
Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu Trp
100 105 110
Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys Asn
115 120 125
Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu Thr
130 135 140
Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys Asp
145 150 155 160
Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn His
165 170 175
Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr Lys
180 185 190
Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg Asn
195 200 205
Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro Ser
210 215 220
Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr Val
225 230 235 240
Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp Ala
245 250 255
Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr Asp
260 265 270
Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe Gly
275 280 285
Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser Trp
290 295 300
Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr Met
305 310 315 320
Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala Lys
325 330 335
Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg Lys
340 345 350
Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe Ala
355 360 365
Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro Thr
370 375 380
Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys Tyr
385 390 395 400
Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp Ala
405 410 415
Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 234
<211> 429
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 234
Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp Asn Ala
1 5 10 15
Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp Met Ser
20 25 30
Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly Gln Gly
35 40 45
Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr Ile Asp
50 55 60
Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys Ile Ser
65 70 75 80
Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe Tyr Met
85 90 95
Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu Trp Arg
100 105 110
Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys Asn Arg
115 120 125
Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu Thr Glu
130 135 140
Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys Asp Phe
145 150 155 160
Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn His Leu
165 170 175
Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr Lys Lys
180 185 190
Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg Asn Asp
195 200 205
Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro Ser Ile
210 215 220
Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr Val Arg
225 230 235 240
Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp Ala Lys
245 250 255
Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr Asp Gln
260 265 270
Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe Gly Glu
275 280 285
Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser Trp Glu
290 295 300
Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr Met Asp
305 310 315 320
Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala Lys Met
325 330 335
Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg Lys Asn
340 345 350
Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe Ala Ile
355 360 365
Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro Thr Leu
370 375 380
Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys Tyr Ser
385 390 395 400
Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp Ala Val
405 410 415
Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425
<210> 235
<211> 419
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 235
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp
<210> 236
<211> 430
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 236
Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp Asn
1 5 10 15
Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp Met
20 25 30
Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly Gln
35 40 45
Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr Ile
50 55 60
Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys Ile
65 70 75 80
Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe Tyr
85 90 95
Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu Trp
100 105 110
Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys Asn
115 120 125
Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu Thr
130 135 140
Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys Asp
145 150 155 160
Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn His
165 170 175
Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr Lys
180 185 190
Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg Asn
195 200 205
Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro Ser
210 215 220
Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr Val
225 230 235 240
Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp Ala
245 250 255
Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr Asp
260 265 270
Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe Gly
275 280 285
Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser Trp
290 295 300
Glu Asn Thr Arg Thr Lys Glu Gln Cys Gln Ala Ile Lys Glu Tyr Met
305 310 315 320
Asp Arg Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala Lys
325 330 335
Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg Lys
340 345 350
Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe Ala
355 360 365
Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro Thr
370 375 380
Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys Tyr
385 390 395 400
Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp Ala
405 410 415
Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 237
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 237
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Ala Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 238
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 238
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Ala Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 239
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 239
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Ala Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 240
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 240
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Ala Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 241
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 241
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Ala Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 242
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 242
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Ala Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 243
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 243
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Ala Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 244
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 244
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Ala Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 245
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 245
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Ala Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 246
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 246
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Ala Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 247
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 247
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Ala Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 248
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 248
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Ala Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 249
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 249
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Ala Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 250
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 250
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Ala Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 251
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 251
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ala Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 252
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 252
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Ala Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 253
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 253
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ala Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 254
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 254
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ala Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 255
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 255
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Ala Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 256
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 256
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Ala
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 257
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 257
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Ala Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 258
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 258
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Ala Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 259
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 259
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Ala Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 260
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 260
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ala Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 261
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 261
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Ala Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 262
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 262
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Ala Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 263
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 263
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ala Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 264
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 264
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Ala
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 265
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 265
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Ala Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 266
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 266
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Ala Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 267
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 267
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Ala Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 268
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 268
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Ala Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 269
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 269
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Ala Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 270
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 270
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ala Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 271
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 271
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Ala Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 272
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 272
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Ala Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 273
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 273
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ala Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 274
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 274
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Ala Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 275
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 275
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Ala Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 276
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 276
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Ala
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 277
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 277
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Ala Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 278
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 278
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Ala Val Cys Ile Asp Ala Phe
420 425 430
<210> 279
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 279
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Ala Cys Ile Asp Ala Phe
420 425 430
<210> 280
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 280
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Ala Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 281
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 281
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Ala Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 282
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 282
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Asn Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 283
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 283
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Gln Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 284
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 284
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Asp Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 285
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 285
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Ile Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 286
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 286
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Gly Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 287
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 287
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Asp Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 288
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 288
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Asp Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 289
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 289
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp His Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 290
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 290
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Lys Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 291
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 291
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Gly Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 292
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 292
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Pro Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 293
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 293
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Met Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 294
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 294
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Phe Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 295
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 295
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Arg Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 296
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 296
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Tyr Cys Ile Asp Ala Phe
420 425 430
<210> 297
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 297
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Thr Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 298
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 298
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Ser Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 299
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 299
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Pro Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 300
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 300
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Met Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 301
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 301
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Ser Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 302
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 302
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Ile Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 303
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 303
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Phe Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 304
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 304
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Phe Thr Arg Thr Gln Glu Ser Cys Gln Ala Ile Gln Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 305
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 305
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Ser Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Ala
130 135 140
Thr Glu Ala Thr Asp Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Asn Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Leu Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Ala Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Asp Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 306
<211> 432
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 306
Asn Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala
1 5 10 15
Trp Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu
20 25 30
Asp Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr
35 40 45
Gly Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro
50 55 60
Tyr Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln
65 70 75 80
Lys Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr
85 90 95
Phe Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu
100 105 110
Glu Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr
115 120 125
Lys Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser
130 135 140
Leu Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly
145 150 155 160
Lys Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro
165 170 175
Asn His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His
180 185 190
Tyr Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys
195 200 205
Arg Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr
210 215 220
Pro Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu
225 230 235 240
Tyr Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro
245 250 255
Asp Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe
260 265 270
Thr Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr
275 280 285
Phe Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly
290 295 300
Ser Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu
305 310 315 320
Tyr Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala
325 330 335
Ala Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile
340 345 350
Arg Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn
355 360 365
Phe Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys
370 375 380
Pro Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser
385 390 395 400
Cys Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr
405 410 415
Asp Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 307
<211> 433
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 307
Leu Asn Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp
1 5 10 15
Ala Trp Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro
20 25 30
Leu Asp Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala
35 40 45
Thr Gly Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr
50 55 60
Pro Tyr Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro
65 70 75 80
Gln Lys Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile
85 90 95
Thr Phe Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp
100 105 110
Glu Glu Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val
115 120 125
Tyr Lys Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu
130 135 140
Ser Leu Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala
145 150 155 160
Gly Lys Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg
165 170 175
Pro Asn His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His
180 185 190
His Tyr Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile
195 200 205
Lys Arg Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu
210 215 220
Tyr Pro Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr
225 230 235 240
Leu Tyr Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile
245 250 255
Pro Asp Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val
260 265 270
Phe Thr Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr
275 280 285
Thr Phe Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp
290 295 300
Gly Ser Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys
305 310 315 320
Glu Tyr Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu
325 330 335
Ala Ala Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys
340 345 350
Ile Arg Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp
355 360 365
Asn Phe Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly
370 375 380
Lys Pro Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys
385 390 395 400
Ser Cys Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp
405 410 415
Thr Asp Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala
420 425 430
Phe
<210> 308
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 308
Phe Lys Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ala Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Ser Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Met
130 135 140
Thr Glu Ala Thr Asp Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Ala Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Leu Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Ala Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Asp Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 309
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 309
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Ala Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Ala
130 135 140
Thr Glu Ala Thr Ala Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Ala Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Leu Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Ala Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Lys Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Asp Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 310
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 310
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Ile Thr Arg Thr Met Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 311
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 311
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Asp
290 295 300
Leu Ser Ile Ser Ser Thr Met Glu Ser Cys Gln Ala Ile Asp Glu Tyr
305 310 315 320
Met Glu Thr Ile Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 312
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 312
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Thr Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Leu
130 135 140
Thr Glu Ala Thr Glu Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Gln Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Ile Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Val Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Asp
290 295 300
Leu Ser Ile Ser Arg Thr Met Glu Ser Cys Gln Ala Ile Asp Glu Tyr
305 310 315 320
Met Glu Thr Ile Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Thr Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 313
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 313
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Ser Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Ala
130 135 140
Thr Glu Ala Thr Asp Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Asn Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Leu Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Ala Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Asn Thr Arg Thr Met Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Asp Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 314
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 314
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Ser Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Ala
130 135 140
Thr Glu Ala Thr Asp Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Asn Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Leu Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Ala Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Ser
290 295 300
Trp Glu Ile Thr Arg Thr Met Glu Ser Cys Gln Ala Ile Lys Glu Tyr
305 310 315 320
Met Asp Thr Thr Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Asp Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 315
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 315
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Ala Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Ala
130 135 140
Thr Glu Ala Thr Ala Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Ala Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Leu Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Ala Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Asp
290 295 300
Leu Ser Ile Ser Ser Thr Met Glu Ser Cys Gln Ala Ile Asp Glu Tyr
305 310 315 320
Met Glu Thr Ile Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Asp Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
<210> 316
<211> 431
<212> PRT
<213> Artificial Sequence
<220>
<223> Artificial Sequence
<400> 316
Phe Arg Ala Pro Pro Val Ile Pro Asn Val Pro Phe Leu Trp Ala Trp
1 5 10 15
Asn Ala Pro Ser Glu Phe Cys Leu Gly Lys Phe Asp Glu Pro Leu Asp
20 25 30
Met Ser Leu Phe Ser Phe Ile Gly Ser Pro Arg Ile Asn Ala Thr Gly
35 40 45
Gln Gly Val Thr Ile Phe Tyr Val Asp Arg Leu Gly Tyr Tyr Pro Tyr
50 55 60
Ile Asp Ser Ile Thr Gly Val Thr Val Asn Gly Gly Ile Pro Gln Lys
65 70 75 80
Ile Ser Leu Gln Asp His Leu Asp Lys Ala Lys Lys Asp Ile Ala Phe
85 90 95
Tyr Met Pro Val Asp Asn Leu Gly Met Ala Val Ile Asp Trp Glu Glu
100 105 110
Trp Arg Pro Thr Trp Ala Arg Asn Trp Lys Pro Lys Asp Val Tyr Lys
115 120 125
Asn Arg Ser Ile Glu Leu Val Gln Gln Gln Asn Val Gln Leu Ser Ala
130 135 140
Thr Glu Ala Thr Ala Lys Ala Lys Gln Glu Phe Glu Lys Ala Gly Lys
145 150 155 160
Asp Phe Leu Val Glu Thr Ile Lys Leu Gly Lys Leu Leu Arg Pro Asn
165 170 175
His Leu Trp Gly Tyr Tyr Leu Phe Pro Asp Cys Tyr Asn His His Tyr
180 185 190
Lys Lys Pro Gly Tyr Asn Gly Ser Cys Phe Asn Val Glu Ile Lys Arg
195 200 205
Asn Asp Asp Leu Ser Trp Leu Trp Asn Glu Ser Thr Ala Leu Tyr Pro
210 215 220
Ser Ile Tyr Leu Asn Thr Ala Gln Ser Pro Val Ala Ala Thr Leu Tyr
225 230 235 240
Val Arg Asn Arg Val Arg Glu Ala Ile Arg Val Ser Lys Leu Pro Asp
245 250 255
Ala Lys Ser Pro Leu Pro Val Phe Ala Tyr Thr Arg Ile Val Phe Thr
260 265 270
Asp Gln Ala Leu Lys Phe Leu Ser Gln Asp Glu Leu Val Tyr Thr Phe
275 280 285
Gly Glu Thr Val Ala Leu Gly Ala Ser Gly Ile Val Ile Trp Gly Asp
290 295 300
Leu Ser Ile Ser Arg Thr Met Glu Ser Cys Gln Ala Ile Asp Glu Tyr
305 310 315 320
Met Glu Thr Ile Leu Asn Pro Tyr Ile Ile Asn Val Thr Leu Ala Ala
325 330 335
Lys Met Cys Ser Gln Val Leu Cys Gln Glu Gln Gly Val Cys Ile Arg
340 345 350
Lys Asn Trp Asn Ser Ser Asp Tyr Leu His Leu Asn Pro Asp Asn Phe
355 360 365
Ala Ile Gln Leu Glu Lys Gly Gly Lys Phe Thr Val Arg Gly Lys Pro
370 375 380
Thr Leu Glu Asp Leu Glu Gln Phe Ser Glu Lys Phe Tyr Cys Ser Cys
385 390 395 400
Tyr Ser Thr Leu Ser Cys Lys Glu Lys Ala Asp Val Lys Asp Asp Asp
405 410 415
Ala Val Asp Val Cys Ile Ala Asp Gly Val Cys Ile Asp Ala Phe
420 425 430
Claims (19)
- 서열번호 3에 따른 아미노산 서열을 갖는 변이체에 있어, 하나 이상의 위치에서 아미노산 잔기의 치환, 삽입 또는 결실을 포함하고 응집온도가 야생형 PH20보다 높은 것을 특징으로 하는 PH20 변이체 또는 이의 절편.
- 제1항에 있어서, 서열번호 3의 아미노산 서열을 갖는 변이체에 있어, R39, D65 내지 L68, N82, T84, I102 내지 I105, T132 내지 Y134, N166, L179 내지 T182, T185 내지 K187, V241 내지 K244, N266 내지 Q269, P271, V272, K290 내지 P292, Q311 내지 K314, G340 내지 N363, L441, S442, D451 내지 D453, D461, V463 및 D461 내지 V463로 구성된 군에서 선택된 하나 이상의 위치에서의 아미노산 잔기의 치환을 포함하는 것을 특징으로 하는 PH20 변이체 또는 이의 절편.
- 제2항에 있어서, 상기 아미노산 잔기의 치환은 R39K, D65A, E66A, P67A, L68A, N82A, T84N, I102A, D103A, S104A, S104N, I105A, I105Q, T132A, T132S, F133A, Y134A, N166A, N166K, L179A, L179S, L179I, L179F, S180T, S180A, L181A, L181M, T182A, T185A, E186A, E186D, K187A, V241A, E242A, I243A, K244A, N266A, T267A, Q268A, Q268D, Q268I, Q268N, Q269A, P271A, V272A, K290A, I291A, I291G, I291L, P292A, P292D, Q311A, V312A, L313A, L313P, L313M, K314A, G340Q, S341H, S341D, S341T, W342I, W342D, W342H, W342L, E343V, E343S, E343Y, E343Q, N344F, N344I, T345E, T345K, T345S, R346M, R346F, R346L, R346T, R346S, R346A, T347Q, T347E, T347V, T347W, T347H, T347S, K348Q, K348F, K348D, K348T, K348E, K348M, E349L, E349W, E349A, S350Q, S350I, S350D, S350T, S350E, S350N, Q352E, Q352G, Q352Y, Q352W, Q352T, A353E, A353Y, A353H, A353K, I354E, I354Q, I354S, I354V, I354A, I354N, I354T, I354R, I354W, I354L, K355Q, K355H, K355D, E356M, E356F, E356I, E356L, E356Q, E356V, E356D, Y357W, Y357F, M358V, M358R, M358Y, M358L, D359K, D359V, D359Y, D359Q, D359T, D359S, D359E, T360Y, T360R, T360L, T360D, T360S, T361M, T361E, T361H, T361L, T361D, T361I, L362A, N363M, N363E, L441A, S442A, D451A, D451S, T452A, T452D, T452H, T452K, T452G, T452P, T452M, T452F, D453A, D461R, D461A, G462A, V463Y 및 V463A로 구성된 군에서 선택된 하나 이상인 것을 특징으로 하는 PH20 변이체 또는 이의 절편.
- 제1항 내지 제3항 중 어느 한 항에 있어서, 추가적으로 C-말단 및/또는 N-말단에서의 일부 아미노산 잔기가 결실된 것을 특징으로 하는 PH20 변이체 또는 이의 절편.
- 제4항에 있어서, N-말단의 M1 내지 P42로 구성된 군에서 선택된 아미노산 잔기 앞에서 절단되어 일부 아미노산 잔기가 결실된 것을 특징으로 하는 PH20 변이체 또는 이의 절편.
- 제5항에 있어서, N-말단의 L36, N37, F38, R39, A40, P41 또는 P42 잔기 앞에서 절단되어 일부 아미노산 잔기가 결실된 것을 특징으로 하는 PH20 변이체 또는 이의 절편.
- 제4항에 있어서, C-말단의 V455 내지 L509로 구성된 군에서 선택된 아미노산 잔기 다음에서 절단되어 일부 아미노산 잔기가 결실된 것을 특징으로 하는 PH20 변이체 또는 이의 절편.
- 제7항에 있어서, C-말단의 V455 내지 S490로 구성된 군에서 선택된 아미노산 잔기 다음에서 절단되어 일부 아미노산 잔기가 결실된 것을 특징으로 하는 PH20 변이체 또는 이의 절편.
- 제7항에 있어서, C-말단의 V455, D456, C458, D461, C464, I465, D466, A467, F468, K470, P471, P472, M473, E474, T475, E476, P478, I480, Y482, A484, P486, T488 또는 S490 잔기 다음에서 절단되어 일부 아미노산 잔기가 결실된 것을 특징으로 하는 PH20 변이체 또는 이의 절편.
- 제4항에 있어서, N-말단의 F38 잔기 앞에서 절단되고, C-말단의 F468 잔기 다음에서 절단되어 일부 아미노산 잔기가 결실된 것을 특징으로 하는 PH20 변이체 또는 이의 절편.
- 제1항 내지 제10항 중 어느 한 항에 있어서, 서열번호 163 내지 서열번호 316의 아미노산 서열로 구성된 군에서 선택되는 것을 특징으로 하는 PH20 변이체 또는 이의 절편.
- 제1항 내지 제11항 중 어느 한 항의 PH20 변이체 또는 이의 절편을 포함하는 암 치료용 조성물.
- 제12항에 있어서, 다른 항암제와의 병용 치료 용도로 사용되는 것을 특징으로 하는 암 치료용 조성물.
- 제13항에 있어서, 상기 다른 항암제는 면역항암제인 것을 특징으로 하는 암치료용 조성물.
- 제14항에 있어서, 상기 면역항암제는 면역체크포인트 저해제(immune checkpoint inhibitor)인 것을 특징으로 하는 암 치료용 조성물.
- 제1항 내지 제11항 중 어느 한 항의 PH20 변이체 또는 이의 절편을 코딩하는 핵산.
- 제16항에 따른 핵산을 포함하는 재조합 발현 벡터.
- 제17항에 따른 재조합 발현 벡터로 형질전환된 숙주세포.
- 제18항에 따른 숙주세포를 배양하는 단계를 포함하는 PH20 변이체 또는 이의 절편의 제조방법.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020200009046 | 2020-01-23 | ||
| KR20200009046 | 2020-01-23 | ||
| PCT/KR2021/000943 WO2021150079A1 (ko) | 2020-01-23 | 2021-01-25 | 안정성이 향상된 신규 히알루론산 가수분해 효소 변이체 및 이를 포함하는 약제학적 조성물 |
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| KR20220069045A true KR20220069045A (ko) | 2022-05-26 |
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| Application Number | Title | Priority Date | Filing Date |
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| KR1020227013211A KR20220069045A (ko) | 2020-01-23 | 2021-01-25 | 안정성이 향상된 신규 히알루론산 가수분해 효소 변이체 및 이를 포함하는 약제학적 조성물 |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US20230250408A1 (ko) |
| EP (1) | EP3992285A4 (ko) |
| JP (2) | JP2022552756A (ko) |
| KR (1) | KR20220069045A (ko) |
| CN (1) | CN113840921A (ko) |
| AU (2) | AU2021211348B2 (ko) |
| BR (1) | BR112021022739A2 (ko) |
| CA (1) | CA3137324A1 (ko) |
| MX (1) | MX2022008060A (ko) |
| TW (2) | TW202302845A (ko) |
| WO (1) | WO2021150079A1 (ko) |
| ZA (1) | ZA202206370B (ko) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023249408A1 (ko) * | 2022-06-22 | 2023-12-28 | (주)알테오젠 | N-말단 및/또는 c-말단이 절단된 가용성 ph20 폴리펩티드 및 이의 용도 |
| WO2024005502A1 (ko) * | 2022-06-29 | 2024-01-04 | 주식회사 오디스젠 | 중성 ph에서 활성을 나타내는 히알루로니다제 hyal1 변이체 |
| KR20240003758A (ko) * | 2022-06-29 | 2024-01-09 | 주식회사 오디스젠 | 중성 pH에서 활성을 나타내는 히알루로니다제 Hyal1변이체 |
| WO2024058648A1 (ko) * | 2022-09-16 | 2024-03-21 | (주)피앤피바이오팜 | 신규한 히알루로니다제 ph-20 변이체 및 그 용도 |
| WO2024196173A1 (ko) * | 2023-03-23 | 2024-09-26 | (주)알테오젠 | 신규 히알루론산 가수분해 효소 변이체 및 이를 포함하는 약제학적 조성물 |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP4267172A1 (en) | 2020-12-28 | 2023-11-01 | Bristol-Myers Squibb Company | Subcutaneous administration of pd1/pd-l1 antibodies |
| EP4267105A1 (en) | 2020-12-28 | 2023-11-01 | Bristol-Myers Squibb Company | Antibody compositions and methods of use thereof |
| PE20241337A1 (es) | 2021-09-14 | 2024-07-03 | Takeda Pharmaceuticals Co | Administracion facilitada de formulaciones concentradas de anticuerpos mediante el uso de hialuronidasa |
| WO2023235847A1 (en) | 2022-06-02 | 2023-12-07 | Bristol-Myers Squibb Company | Antibody compositions and methods of use thereof |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20160052812A (ko) * | 2008-04-14 | 2016-05-12 | 할로자임, 아이엔씨 | 히알루로난 관련 질환 및 상태 치료용 변형된 히알루로니다제 및 그 용도 |
| CN103205407B (zh) * | 2008-12-09 | 2016-03-16 | 哈洛齐梅公司 | 延长的可溶性ph20多肽及其用途 |
| ES2749620T3 (es) * | 2011-12-30 | 2020-03-23 | Halozyme Inc | Variantes de polipéptidos de PH20, formulaciones y usos de los mismos |
| TW201534726A (zh) * | 2013-07-03 | 2015-09-16 | Halozyme Inc | 熱穩定ｐｈ２０玻尿酸酶變異體及其用途 |
| KR102151388B1 (ko) | 2018-07-25 | 2020-09-04 | (주)알테오젠 | 효소 활성과 열 안정성이 증가한 새로운 히알루론산 가수분해 효소 및 이의 제조방법 |
| EA202192588A1 (ru) * | 2019-03-25 | 2022-03-17 | Алтеоген Инк. | Фармацевтическая композиция, включающая вариант ph20 гиалуронидазы человека, и лекарственное средство для подкожного введения |
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2021
- 2021-01-25 CN CN202180003323.4A patent/CN113840921A/zh active Pending
- 2021-01-25 KR KR1020227013211A patent/KR20220069045A/ko not_active Application Discontinuation
- 2021-01-25 MX MX2022008060A patent/MX2022008060A/es unknown
- 2021-01-25 BR BR112021022739A patent/BR112021022739A2/pt unknown
- 2021-01-25 AU AU2021211348A patent/AU2021211348B2/en active Active
- 2021-01-25 JP JP2021567961A patent/JP2022552756A/ja active Pending
- 2021-01-25 TW TW111136059A patent/TW202302845A/zh unknown
- 2021-01-25 EP EP21743774.8A patent/EP3992285A4/en active Pending
- 2021-01-25 TW TW110102662A patent/TW202140780A/zh unknown
- 2021-01-25 US US17/608,729 patent/US20230250408A1/en active Pending
- 2021-01-25 CA CA3137324A patent/CA3137324A1/en active Pending
- 2021-01-25 WO PCT/KR2021/000943 patent/WO2021150079A1/ko unknown
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2022
- 2022-06-08 ZA ZA2022/06370A patent/ZA202206370B/en unknown
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2024
- 2024-01-05 AU AU2024200091A patent/AU2024200091A1/en not_active Abandoned
- 2024-03-14 JP JP2024039952A patent/JP2024095673A/ja active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023249408A1 (ko) * | 2022-06-22 | 2023-12-28 | (주)알테오젠 | N-말단 및/또는 c-말단이 절단된 가용성 ph20 폴리펩티드 및 이의 용도 |
| KR102682612B1 (ko) * | 2022-06-22 | 2024-07-10 | (주)알테오젠 | N-말단 및/또는 c-말단이 절단된 가용성 ph20 폴리펩티드 및 이의 용도 |
| WO2024005502A1 (ko) * | 2022-06-29 | 2024-01-04 | 주식회사 오디스젠 | 중성 ph에서 활성을 나타내는 히알루로니다제 hyal1 변이체 |
| KR20240003758A (ko) * | 2022-06-29 | 2024-01-09 | 주식회사 오디스젠 | 중성 pH에서 활성을 나타내는 히알루로니다제 Hyal1변이체 |
| WO2024058648A1 (ko) * | 2022-09-16 | 2024-03-21 | (주)피앤피바이오팜 | 신규한 히알루로니다제 ph-20 변이체 및 그 용도 |
| WO2024196173A1 (ko) * | 2023-03-23 | 2024-09-26 | (주)알테오젠 | 신규 히알루론산 가수분해 효소 변이체 및 이를 포함하는 약제학적 조성물 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP3992285A1 (en) | 2022-05-04 |
| AU2021211348B2 (en) | 2023-10-05 |
| BR112021022739A2 (pt) | 2022-08-09 |
| JP2022552756A (ja) | 2022-12-20 |
| TW202302845A (zh) | 2023-01-16 |
| US20230250408A1 (en) | 2023-08-10 |
| ZA202206370B (en) | 2023-06-28 |
| EP3992285A4 (en) | 2023-01-25 |
| MX2022008060A (es) | 2022-07-27 |
| CN113840921A (zh) | 2021-12-24 |
| JP2024095673A (ja) | 2024-07-10 |
| AU2021211348A1 (en) | 2021-12-09 |
| WO2021150079A1 (ko) | 2021-07-29 |
| TW202140780A (zh) | 2021-11-01 |
| CA3137324A1 (en) | 2021-07-29 |
| AU2024200091A1 (en) | 2024-01-25 |
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