製備多聚體蛋白質的方法和相關的組合物的製作方法

2023-06-14 10:28:36 2

專利名稱：製備多聚體蛋白質的方法和相關的組合物的製作方法
技術領域：
本發明涉及多聚體蛋白質複合物、氧還蛋白和重組多肽；以及製備它們的改良方法。
背景技術：
多聚體蛋白(即，包含多個多肽鏈的蛋白質)是一類具有生物學和商業重要性的蛋白質。例如，抗體是可以用於治療多種疾病的多聚體蛋白質。然而，鑑於其複雜性，多聚體蛋白常常為製備造成顯著的困難。
氧還蛋白也是一種商業上重要的蛋白質，可應用於各種不同的產業中，包括製藥業、個人護理和食品業。例如，硫氧還蛋白這種氧還蛋白可以用於製備個人護理產品(日本專利申請JP 9012471A2，JP103743A2，JP 1129785A2)、藥物組合物/產品(Aota等(1996)J.cardiov.Pharmacol.(1996)27727-732)以及減少食品如奶(del Val等(1999)J.allerg.Vlin.Immunol.103690-697)和小麥(Buchanan等(1997)Proc.Natl.Acad.Sci.USA 945372-5377)中存在的蛋白質變應原。
然而，本領域仍需要進一步改良用於重組表達多聚體蛋白，包括氧還蛋白的這些方法。本發明滿足了此需要並提供了相關的優點。
發明概述本發明涉及與油體結合用於製備第一和/或第二重組多肽、多聚體蛋白質複合物、異源多聚體蛋白複合物、多聚體融合蛋白(multimeric-fusion-proteins)、異源多聚體融合蛋白、免疫球蛋白多肽鏈、免疫球蛋白、氧還蛋白融合多肽和/或硫氧還蛋白相關蛋白的改良新方法。因此，本文提供製備重組多聚體蛋白質複合物的方法，所述方法包括(a)在包含油體的細胞中生產第一重組多肽和第二重組多肽，其中所述第一重組多肽能夠與所述第二重組多肽結合形成所述多聚體蛋白複合物；和(b)通過能夠結合所述油體和所述第一重組多肽的油體靶向蛋白使所述多聚體蛋白複合物與油體結合。
該方法還考慮分離與所述重組多聚體蛋白複合物結合的油體。第二重組多肽可以與能夠結合油體和第二重組多肽的第二油體靶向蛋白結合。所述油體靶向蛋白均可以是油體蛋白也可以是免疫球蛋白。油體靶向蛋白可以是油質蛋白或caleosin。當油體靶向蛋白是油質蛋白或caleosin時，第一重組多肽可以和所述油質蛋白或caleosin融合。同樣，第二重組多肽可以和能夠結合油體的第二油質蛋白或第二caleosin融合。第一和第二重組多肽可以以包括所述第一和第二多肽的多聚體融合蛋白形式產生，並可以形成多聚體蛋白複合物。該多聚體蛋白複合物可以是異源多聚體蛋白複合物，而異源多聚體蛋白複合物可以是具有酶學活性的氧還蛋白複合物或免疫球蛋白。在一個實施方案中，第一重組多肽能夠與第二重組多肽在細胞中結合。在另一實施方案中，第一重組多肽可以是硫氧還蛋白而第二重組多肽可以是硫氧還蛋白還原酶。在特定的實施方案中，該硫氧還蛋白可以選自SEQ ID NOs38、42、46、50和SEQ ID NOs52-194；而硫氧還蛋白還原酶可以選自SEQ ID NOs8、9、10、40、44、48、50和SEQ ID NOs195-313。在另一實施方案中，第一重組多肽可以是免疫球蛋白多肽鏈。例如，第一重組多肽可以是免疫球蛋白輕鏈或其免疫學活性部分，而第二重組多肽可以是免疫球蛋白重鏈或其免疫學活性部分。在此實施方案中，油體靶向蛋白可以包括A蛋白、L蛋白或G蛋白。細胞可以是植物細胞，如紅花細胞等。
本文還提供在細胞中表達包含第一和第二重組多肽的重組多聚體蛋白複合物的方法，所述方法包括(a)向細胞中引入第一嵌合核酸序列，其包含(i)能夠在所述細胞中調節轉錄的第一核酸序列；(ii)與(i)可操作連接的、編碼第一重組多肽的第二核酸序列；(b)向所述細胞中引入第二嵌合核酸序列，其包含(i)能夠在所述細胞中調節轉錄的第三核酸序列；(ii)與(i)可操作連接的、編碼第二重組多肽的第四核酸序列；(c)在允許所述第一和第二重組多肽在包含油體的子代細胞中表達的條件下培養所述細胞，其中所述第一重組多肽和第二重組多肽能夠形成多聚體蛋白複合物；和(d)通過能結合所述油體和所述第一重組多肽的油體靶向蛋白使所述第一重組多肽和油體結合。該方法還考慮從子代細胞中分離出包含此多聚體蛋白複合物的油體。第二重組多肽可以與能夠結合油體和第二重組多肽的第二油體靶向蛋白結合。所述油體靶向蛋白每種均可以是油體蛋白質或免疫球蛋白。油體靶向蛋白可以是油質蛋白或caleosin。當油體靶向蛋白是油質蛋白或caleosin時，第一重組多肽可以和所述油質蛋白或caleosin融合。同樣，第二重組多肽可以和能夠與油體結合的第二油質蛋白或第二caleosin融合。第一和第二重組多肽可以以包含所述第一和第二多肽的多聚體融合蛋白的形成產生，也可以形成多聚體蛋白複合物。此多聚體蛋白複合物可以是異源多聚體蛋白複合物，而此異源多聚體蛋白複合物可以是具有酶學活性的氧還蛋白複合物或免疫球蛋白。在一個實施方案中，第一重組多肽能夠與第二重組多肽在所述子代細胞中形成多聚體蛋白複合物。在另一實施方案中，第一重組多肽可以是硫氧還蛋白而第二重組多肽可以是硫氧還蛋白還原酶。在特定的實施方案中，該硫氧還蛋白可以選自SEQ ID NOs38、42、46、50和SEQ ID NOs52-194；而硫氧還蛋白還原酶可以選自SEQ ID NOs8、9、10、40、44、48、50和SEQ ID NOs195-313。在另一實施方案中，第一重組多肽可以是免疫球蛋白多肽鏈。例如，第一重組多肽可以是免疫球蛋白輕鏈或其免疫學活性部分，而第二重組多肽可以是免疫球蛋白重鏈或其免疫學活性部分。在此實施方案中，油體靶向蛋白可以包括A蛋白、L蛋白或G蛋白。細胞可以是植物細胞，如紅花細胞等。
本文還提供在植物中生產重組多聚體蛋白複合物的方法，所述方法包括(a)製備包含如下細胞的第一植物，所述細胞包含油體和第一重組多肽，其中所述第一重組多肽能夠通過油體靶向蛋白與所述油體結合；(b)製備包含如下細胞的第二植物，所述細胞包含油體和第二重組多肽；和(c)使所述第一植物和所述第二植物進行有性雜交產生包含如下細胞的子代植物，所述細胞包含油體，其中所述油體能夠與所述第一重組多肽結合，而所述第一重組多肽能夠與所述第二重組多肽結合形成所述重組多聚體蛋白複合物。在第二植物中第二重組多肽可以通過第二油體靶向蛋白與油體結合。可以從包含所述多聚體蛋白複合物的子代植物中分離油體。油體靶向蛋白可以選自油體蛋白或免疫球蛋白，其中油體蛋白可以是油質蛋白或caleosin。第一重組多肽可以和油質蛋白或caleosin融合；而第二重組多肽可以和能夠與油體結合的第二油質蛋白或第二caleosin融合。第一和第二重組多肽可以形成多聚體蛋白複合物，如異源多聚體蛋白複合物，其中此異源多聚體蛋白複合物可以是具有酶學活性的氧還蛋白複合物或免疫球蛋白。在特定的實施方案中，第一重組多肽是硫氧還蛋白，而第二重組多肽是硫氧還蛋白還原酶。該硫氧還蛋白可以選自SEQ ID NOs38、42、46、50和SEQ ID NOs52-194；而硫氧還蛋白還原酶可以選自SEQ ID NOs8、9、10、40、44、48、50和SEQ ID NOs195-313。在另一實施方案中，第一重組多肽可以是免疫球蛋白多肽鏈。例如，第一重組多肽可以是免疫球蛋白輕鏈或其免疫學活性部分，而第二重組多肽可以是免疫球蛋白重鏈或其免疫學活性部分。在此實施方案中，油體靶向蛋白可以包括A蛋白、L蛋白或G蛋白。細胞可以是植物細胞，如紅花細胞等。
本文還提供編碼本文所述多聚體融合蛋白的嵌合核酸，所述核酸包含(a)編碼油體靶向蛋白的第一核酸序列；(b)在閱讀框中與(a)可操作連接的、編碼第一重組多肽的第二核酸序列；(c)在閱讀框中與(b)可操作連接的、編碼第二重組多肽的第三核酸序列；其中所述第一和第二重組多肽能夠形成多聚體蛋白複合物。油體靶向蛋白可以選自油體蛋白質或免疫球蛋白。油體蛋白可以是油質蛋白或caleosin。此多聚體蛋白複合物可以是異源多聚體蛋白複合物，第一和第二重組多肽可以形成具有酶學活性的異源多聚體氧還蛋白複合物或免疫球蛋白。在一個特定實施方案中，第一重組多肽是硫氧還蛋白而第二重組多肽是硫氧還蛋白還原酶。該硫氧還蛋白可以選自SEQ ID NOs38、42、46、50和SEQ ID NOs52-194；而硫氧還蛋白還原酶可以選自SEQID NOs8、9、10、40、44、48、50和SEQ ID NOs195-313。在另一實施方案中，第一重組多肽可以是免疫球蛋白多肽鏈。例如，第一重組多肽可以是免疫球蛋白輕鏈或其免疫學活性部分，而第二重組多肽可以是免疫球蛋白重鏈或其免疫學活性部分。在此實施方案中，油體靶向蛋白可以包括A蛋白、L蛋白或G蛋白。在再一實施方案中，可以在編碼油體靶向蛋白的核酸序列和編碼第一重組多肽的核酸序列之間放置接頭核酸序列，其編碼迴避油體表面的接頭胺基酸序列。迴避油體表面的接頭胺基酸序列可以實質上帶有負電荷，或具有至少35kd的分子量。任選地，該基因融合物還可以包含編碼能夠被酶或化學物質特異切割的胺基酸序列的接頭核酸序列，其中該接頭序列位於迴避油體表面的接頭胺基酸序列(非蛋白水解接頭)和所述編碼第一重組多肽的序列之間。
本文還提供重組多聚體融合蛋白，其包含(i)油體靶向蛋白或其片斷，(ii)第一重組多肽和(iii)第二重組多肽，其中所述第一和第二重組多肽能夠形成多聚體蛋白複合物。油體靶向蛋白選自油體蛋白或免疫球蛋白，而油體蛋白可以是油質蛋白或caleosin。多聚體融合蛋白可以是異源多聚體融合蛋白，其中所述第一和第二重組多肽形成具有酶學活性的異源多聚體氧還蛋白複合物或免疫球蛋白。在一個特定實施方案中，第一重組多肽是是硫氧還蛋白而第二重組多肽是硫氧還蛋白還原酶。該硫氧還蛋白可以選自SEQ ID NOs38、42、46、50和SEQ ID NOs52-194；而硫氧還蛋白還原酶可以選自SEQ ID NOs8、9、10、40、44、48、50和SEQ ID NOs195-313。在另一實施方案中，第一重組多肽可以是免疫球蛋白多肽鏈。例如，第一重組多肽可以是免疫球蛋白輕鏈或其免疫學活性部分，而第二重組多肽可以是免疫球蛋白重鏈或其免疫學活性部分。在此實施方案中，油體靶向蛋白可以包括A蛋白、L蛋白或G蛋白。在再一實施方案中，可以在編碼油體靶向蛋白的核酸序列和編碼第一重組多肽的核酸序列之間放置接頭核酸序列，其編碼迴避油體表面的接頭胺基酸序列。迴避油體表面的接頭胺基酸序列可以實質上帶有負電荷，或具有至少35kd的分子量。任選地，該基因融合物還可以包含編碼能夠被酶或化學物質特異切割的胺基酸序列的接頭核酸序列，其中該接頭序列位於迴避油體表面的接頭胺基酸序列和所述編碼第一重組多肽的序列之間。
本文還提供包含多聚體蛋白複合物的分離的油體，所述多聚體蛋白複合物包含(i)油體靶向蛋白和(ii)第一重組多肽，而所述油體還包含第二重組多肽，其中所述第一和第二重組多肽能形成多聚體蛋白複合物。油體靶向蛋白可以選自油體蛋白或免疫球蛋白，而油體蛋白可以是油質蛋白或caleosin。多聚體融合蛋白可以是異源多聚體融合蛋白，其中所述第一和第二重組多肽形成具有酶學活性的異源多聚體氧還蛋白複合物或免疫球蛋白。在一個特定實施方案中，第一重組多肽是硫氧還蛋白，而第二重組多肽是硫氧還蛋白還原酶。在另一實施方案中，第一重組多肽可以是免疫球蛋白多肽鏈。例如，第一重組多肽可以是免疫球蛋白輕鏈或其免疫學活性部分，而第二重組多肽可以是免疫球蛋白重鏈或其免疫學活性部分。在此實施方案中，油體靶向蛋白可以包括A蛋白、L蛋白或G蛋白。
本文還提供分離的油體，其包含(a)包含與第一重組多肽融合的第一油體靶向蛋白的第一融合蛋白；和(b)包含與第二重組多肽融合的第二油體靶向蛋白的第二融合蛋白；其中所述第一和第二重組多肽能夠形成多聚體蛋白複合物。油體靶向蛋白可以選自油體蛋白或免疫球蛋白，而油體蛋白可以是油質蛋白或caleosin。多聚體融合蛋白可以是異源多聚體融合蛋白，其中所述第一和第二重組多肽形成具有酶學活性的異源多聚體氧還蛋白複合物或免疫球蛋白。在一個特定實施方案中，第一重組多肽是硫氧還蛋白，而第二重組多肽是硫氧還蛋白還原酶。該硫氧還蛋白可以選自SEQ ID NOs38、42、46、50和SEQ ID NOs52-194；而硫氧還蛋白還原酶可以選自SEQID NOs8、9、10、40、44、48、50和SEQ ID NOs195-313。在另一實施方案中，第一重組多肽可以是免疫球蛋白多肽鏈。例如，第一重組多肽可以是免疫球蛋白輕鏈或其免疫學活性部分，而第二重組多肽可以是免疫球蛋白重鏈或其免疫學活性部分。在此實施方案中，油體靶向蛋白可以包括A蛋白、L蛋白或G蛋白。
本文還提供包含本文所述油體、多聚體蛋白複合物和多聚體融合蛋白的細胞或轉基因植物。在一個實施方案中，第一重組多肽是免疫球蛋白多肽鏈。例如，第一重組多肽可以是免疫球蛋白輕鏈或其免疫學活性部分，而第二重組多肽可以是免疫球蛋白重鏈或其免疫學活性部分。在此實施方案中，油體靶向蛋白可以包括A蛋白、L蛋白或G蛋白。在其中所述第一重組多肽是硫氧還蛋白而所述第二重組多肽是硫氧還蛋白還原酶的實施方案中，可以採用本文所述方法配製可以用於食品、個人護理產品或藥物組合物生產中的油體。這些製劑還可以包含額外的NADP或NADPH。所述食品可以是以奶或小麥為基礎的食品。所述個人護理產品可以用於降低人體表面的氧化壓力或可以用於增亮皮膚。所述藥物組合物可以用於治療慢性阻塞性肺病(COPD)、白內障、糖尿病、螫刺毒作用、支氣管肺病、惡性腫瘤、銀屑病、再灌注損傷、傷口癒合、膿毒病、GI出血、腸道疾病(intestinal bowel disease)(IBD)、潰瘍、GERD(胃食管反流病)。
本文還提供包含分離的油體、硫氧還蛋白和硫氧還蛋白還原酶的組合物，所述硫氧還蛋白可以選自SEQ ID NOs38、42、46、50和SEQ ID NOs52-194；而所述硫氧還蛋白還原酶可以選自SEQ ID NOs8、9、10、40、44、48、50和SEQ ID NOs195-313。該組合物還可以包含NADP或NADPH。在另一實施方案中，組合物包含可以是免疫球蛋白多肽鏈的第一重組多肽和第二重組蛋白。例如，第一重組多肽可以是免疫球蛋白輕鏈或其免疫學活性部分，而第二重組多肽可以是免疫球蛋白重鏈或其免疫學活性部分。在此實施方案中，油體靶向蛋白可以包括A蛋白、L蛋白或G蛋白。
本文還提供多聚體融合蛋白，其中該融合蛋白含有兩個或多個選自圖5所示蛋白的多肽鏈。還提供降低食物的變應原性(allergenicity)的方法，包括步驟提供本文所述分離的油體；和將此分離的油體加入食物中，由此降低食物的變應原性。所述食物可以選自小麥麵粉、小麥麵團、奶、乾酪、酸牛奶和冰淇淋。處理食物的各種方法可以還包括在實質上缺少NADPH時提供NADH作為輔因子。
本文還提供治療或保護靶對象使其免受氧化壓力的方法，包括步驟提供包含硫氧還蛋白和硫氧還蛋白還原酶的重組氧還蛋白融合多肽；和使該重組融合多肽和易受氧化壓力影響的靶對象接觸，由此達到抵抗壓力的治療或保護作用。所述靶對象可以選自分子、分子複合物、細胞、組織和器官。
本文還提供製備與油體結合的酶學活性氧還蛋白的方法，包括a)在細胞中製備包含第一氧還蛋白及與其連接的第二氧還蛋白的氧還蛋白融合多肽；b)通過能夠結合所述氧還蛋白融合多肽和所述油體的油體靶向蛋白使所述氧還蛋白融合多肽與油體結合；和c)分離與所述氧還蛋白融合多肽結合的油體。第一氧還蛋白可以是硫氧還蛋白而第二氧還蛋白可以是硫氧還蛋白還原酶。
本文還提供製備免疫球蛋白的方法，所述方法包括(a)在包含油體的細胞中生產第一免疫球蛋白多肽鏈和第二免疫球蛋白多肽鏈，其中所述第一免疫球蛋白多肽鏈能夠與第二免疫球蛋白多肽鏈結合形成所述免疫球蛋白；和(b)通過能夠結合所述油體和所述第一免疫球蛋白多肽鏈的油體靶向蛋白使所述免疫球蛋白與油體結合。例如，第一免疫球蛋白多肽鏈可以是免疫球蛋白輕鏈或其免疫學活性部分，而第二免疫球蛋白多肽鏈可以是免疫球蛋白重鏈或其免疫學活性部分。在此實施方案中，油體靶向蛋白可以包括A蛋白、L蛋白或G蛋白。
本文還提供製備與油體結合的氧還蛋白或免疫球蛋白的方法，包括a)向細胞中引入包含如下成分的嵌合核酸序列1)能夠在所述細胞中調節轉錄的第一核酸序列；2)與第一核酸序列可操作連接的編碼重組融合多肽的第二核酸序列，其包含(i)編碼足以使所述重組融合多肽靶向油體的油體蛋白部分的核酸序列，(ii)與(i)連接的、編碼氧還蛋白融合多肽(包含相互連接的第一氧還蛋白和第二氧還蛋白)的核酸序列或編碼免疫球蛋白(包含相互連接的第一免疫球蛋白多肽鏈和第二免疫球蛋白多肽鏈)的核酸序列；3)與第二核酸序列可操作連接的能夠在所述細胞中終止轉錄的第三核酸序列；b)在允許所述氧還蛋白融合多肽或免疫球蛋白在包含油體的子代細胞中表達的條件下培養所述細胞；和c)從所述子代細胞中分離包含所述氧還蛋白融合多肽或免疫球蛋白的所述油體。在某些實施方案中，可以在所述編碼足夠的油體蛋白部分的核酸序列和所述編碼氧還蛋白融合多肽或免疫球蛋白的核酸序列之間放置接頭核酸序列，其編碼迴避油體表面的接頭胺基酸序列。迴避油體表面的接頭胺基酸序列可以實質上帶有負電荷，或具有至少35kd的分子量。任選地，該基因融合物還可以包含編碼能夠被酶或化學物質特異切割的胺基酸序列的接頭核酸序列，其中該接頭序列位於迴避油體表面的接頭胺基酸序列和所述編碼氧還蛋白融合多肽的核酸序列之間。在此任選實施方案中，還可以考慮引入能夠切開所述氧還蛋白融合多肽和所述油體的酶或化學物質，由此獲得分離的氧還蛋白融合多肽。第一氧還蛋白可以是硫氧還蛋白而第二氧還蛋白可以是硫氧還蛋白還原酶。在一個實施方案中，該硫氧還蛋白和硫氧還蛋白還原酶可以從鼠耳芥屬(Arabidopsis)獲得。在另一實施方案中，第一氧還蛋白以氧還蛋白融合多肽形式產生時比僅以第一氧還蛋白而沒有第二氧還蛋白產生時活性至少高5倍。
本文還提供利用本文所述各種方法配製與氧還蛋白融合多肽結合的油體乳劑，用於製備能夠治療靶對象的氧化壓力的產品、能夠化學還原靶對象的產品、藥物組合物、個人護理產品或食品。因此，本文提供乳劑製品組合物。
本文還提供嵌合核酸，其包含1)能夠在宿主細胞中調節轉錄的第一核酸序列；2)與1)可操作連接的編碼重組融合多肽的第二核酸序列，其包含(i)編碼足以使所述重組融合多肽靶向油體的油體蛋白部分的核酸序列和與之連接的(ii)編碼氧還蛋白融合多肽(包含相連接的第一氧還蛋白和第二氧還蛋白)的核酸序列；3)與2)可操作連接的能在所述細胞中終止轉錄的第三核酸序列。油體蛋白可以是油質蛋白或caleosin，第一氧還蛋白可以是硫氧還蛋白而第二氧還蛋白可以是硫氧還蛋白還原酶。在某些實施方案中，可以在所述編碼足夠的油體蛋白部分的核酸序列和所述編碼氧還蛋白融合多肽的核酸序列之間放置接頭核酸序列，其編碼迴避油體表面的接頭胺基酸序列。迴避油體表面的接頭胺基酸序列可以實質上帶有負電荷，或具有至少35kd的分子量。在一個實施方案中，該基因融合物還可以任選地包含編碼能夠被酶或化學物質特異切割的胺基酸序列的接頭核酸序列，其中該接頭序列位於迴避油體表面的接頭胺基酸序列和所述編碼氧還蛋白融合多肽的核酸序列之間。
本文還提供包含本文所述的任何嵌合核酸序列和構建體的轉基因植物，例如紅花植物。嵌合核酸可以包含在質體中。因此，本文提供其中含有嵌合核酸的分離的質體。本文還提供包含本文提供的嵌合核酸的植物種子。
本文還提供使用本文提供的任一方法獲得的油體製品，和含有此油體製品的食品、藥物組合物及個人護理產品。本文提供的這些產品和/或組合物能夠治療靶對象的氧化壓力，能夠化學還原靶對象。本文還提供包含能夠化學還原靶對象的油體製品的去汙劑組合物，以及清潔物體的相關方法，該方法包括在促進清潔的條件下向物體施用此產品。
本文還提供包含基因融合物的核酸構建體，其中該基因融合物包含相互可操作連接的編碼油體蛋白或其活性片斷的第一區和編碼至少一個硫氧還蛋白相關蛋白或其活性片斷的第二區。在一個實施方案中，所述至少一個硫氧還蛋白相關蛋白可以是硫氧還蛋白。該硫氧還蛋白可以選自SEQ ID NOs38、42、46、50和SEQ ID NOs52-194，並可以從鼠耳芥屬或小麥中獲得。
在另一實施方案中，所述至少一個硫氧還蛋白相關蛋白可以是硫氧還蛋白還原酶。該硫氧還蛋白還原酶可以選自SEQ ID NOs8、9、10、40、44、48、50和SEQ ID NOs195-313，和/或來源於鼠耳芥屬或小麥。該硫氧還蛋白還原酶可以是NADPH-依賴性硫氧還蛋白還原酶。所述第二區可以編碼硫氧還蛋白和硫氧還蛋白還原酶。在一個實施方案中，硫氧還蛋白和硫氧還蛋白還原酶從麻風分枝桿菌(Mycobacterium leprae)獲得。在另一實施方案中，所述至少一個硫氧還蛋白相關蛋白可以是工程化的融合蛋白。第一區可以以5』至3』的方向位於第二區之前。或者，第一區可以以5』至3』的方向尾隨於第二區之後。基因融合物可以任選地再包含與第一區或第二區或兩者可操作連接的、編碼第二硫氧還蛋白相關蛋白或其活性片斷的第三區。可以使該基因融合物與種子特異性啟動子如菜豆蛋白啟動子可操作地連接。在一個實施方案中，至少一個硫氧還蛋白相關多肽來源於選自鼠耳芥屬或小麥的植物物種。在另一實施方案中，至少一個硫氧還蛋白相關蛋白可以來源於大腸桿菌(E.coli)。
在一個實施方案中，基因融合物還包含編碼迴避油體表面的接頭胺基酸序列的核酸序列，其中該接頭胺基酸序列位於第一區和第二區之間。迴避油體表面的接頭胺基酸序列可以實質上帶負電荷或具有至少35kd的分子量。此外，基因融合物還可以包含編碼能夠被酶或化學物質特異切割的胺基酸序列的接頭核酸序列，其中該接頭序列位於迴避油體表面的接頭胺基酸序列和第二區之間。
本文還提供含有包含基因融合物的核酸構建體的轉基因植物，其中基因融合物包含相互可操作連接的編碼油體蛋白或其活性片斷的區域和編碼第一硫氧還蛋白相關蛋白或其活性片斷的區域。該硫氧還蛋白相關蛋白可以是硫氧還蛋白。核酸構建體可以包含在質體中。在一個實施方案中，當所述第一硫氧還蛋白相關蛋白是硫氧還蛋白時，構建體還可以包含編碼硫氧還蛋白還原酶的區域。基因融合物可以任選地再包含可操作地與第一區或第二區或兩者連接的編碼第二硫氧還蛋白相關蛋白或其活性片斷的第三區域。基因融合物還可以任選地包含編碼迴避油體表面的接頭胺基酸序列的核酸序列，其中編碼該接頭胺基酸序列的核酸位於編碼油體蛋白的區域和編碼第一硫氧還蛋白相關蛋白的區域之間。迴避油體表面的接頭胺基酸序列可以實質上帶負電荷或具有至少35kd的分子量。基因融合物還可以任選地包含編碼能夠被酶或化學物質特異切割的胺基酸序列的接頭核酸序列，其中該接頭序列位於迴避油體表面的接頭胺基酸序列和編碼第一硫氧還蛋白相關蛋白的區域之間。
本文還提供包含核酸構建體，即與基因融合物可操作連接的種子特異性啟動子的轉基因植物，其中基因融合物包含編碼油體蛋白或其活性片斷的區域和與之可操作連接的編碼第一硫氧還蛋白相關蛋白或其活性片斷的區域，其中包含油質蛋白及硫氧還蛋白相關蛋白的活性的融合蛋白在植物的種子中產生。在另一實施方案中，提供濃度至少為總細胞種子蛋白大約0.5％的硫氧還蛋白相關蛋白。本文還提供包含硫氧還蛋白相關蛋白的活性的提取物。還提供從各種種子獲得的油體和/或油。
本文還提供製備包含硫氧還蛋白相關活性的融合蛋白的方法，該方法包括步驟a)提供包含核酸構建體的轉基因植物，所述核酸構建體包含可操作地連接基因融合物的種子特異性啟動子，其中基因融合物包含編碼油體蛋白或其活性片斷的區域和與之可操作連接的編碼第一硫氧還蛋白相關蛋白或其活性片斷的區域，該基因融合物編碼包含硫氧還蛋白相關活性的融合蛋白；b)從該植物獲得種子；和c)通過從種子中分離油體回收此融合蛋白。在一個實施方案中，對油體進行分級分離以便部分純化此融合蛋白。油體可以和融合蛋白結合。可以在分級分離油體後將油體蛋白和硫氧還蛋白相關蛋白切開。切割步驟可以利用蛋白酶或化學蛋白水解進行。
本文還提供降低食物變應原性的方法，包括步驟a)提供包含與融合蛋白結合的油體的製品，該融合蛋白包含油體蛋白或其活性片斷以及硫氧還蛋白相關蛋白或其活性片斷；和b)將此製品加入食物中，由於硫氧還蛋白相關蛋白或片斷的活性，食物的變應原性得以降低。所述食物可以是小麥麵粉、小麥麵團、奶、乾酪、酸牛奶和冰淇淋。在一個實施方案中，在實質上缺少NADPH時使用NADH作為輔因子。
本文還提供在可藥用載體中包含融合蛋白的藥物組合物，所述融合蛋白包含油體蛋白或其活性片斷以及硫氧還蛋白相關蛋白或其活性片斷。油體可以與融合蛋白結合。本文還提供在可藥用載體中包含與融合蛋白結合的油體的化妝品製劑，所述融合蛋白包含油體蛋白或其活性片斷以及硫氧還蛋白相關蛋白或其活性片斷。還提供治療或保護靶對象使其免受氧化壓力的方法，包括步驟a)提供包含融合蛋白的製品，所述融合蛋白包含油體蛋白或其活性片斷以及硫氧還蛋白相關蛋白或其活性片斷；和b)使製品與靶對象接觸，其中所述靶對象對氧化壓力具有易感性，由此達到抵抗壓力的治療或保護作用。靶對象可以選自分子、分子複合物、細胞、組織和器官。
本文還提供包含基因融合物的核酸構建體，其中基因融合物包含編碼油體蛋白或其活性片斷的第一區及與之可操作連接的編碼至少一個多肽或其活性片斷的第二區和在閱讀框中位於第一和第二區多肽之間的迴避油體表面的接頭。本文還提供使此構建體表達為編碼的胺基酸序列的方法；以及包含此構建體和編碼的胺基酸序列的油體、製劑、乳劑、細胞和植物。這些具體構建體、油體、製劑、乳劑、細胞和植物可以根據本文描述的方法製備。第二區可以編碼任何多肽，例如，治療上、營養上、工業上或化妝上有用的肽，見本文所述。例如，第二區可以編碼氧還蛋白、免疫球蛋白、硫氧還蛋白相關蛋白或多聚體蛋白複合物中的任何一種或多種重組多肽。
本發明其它特徵和優點鑑於如下的詳細描述將是十分明顯的。然而，應當理解，此發明詳述和具體實施例在指出本發明特定實施方案的同時僅是以舉例說明的方式給出的。
附圖簡述

圖1顯示公布的NADPH硫氧還蛋白還原酶核酸序列(SEQ ID NO9)(ATTHIREDB-Jacquot等，J.Mol.Biol.(1994)235(4)1357-63)與此處實施例1中分離的序列(TR；SEQ ID NO8)的ClustalW格式的比對比較。
圖2顯示此公布的NADPH硫氧還蛋白還原酶序列的推導胺基酸序列(SEQ ID NO12)(ATTHIREDB Jacquot等，J.Mol.Biol.(1994)235(4)1357-63)與此處實施例1中分離的序列(TR；SEQ ID NO13)的ClustalW格式的比對。
圖3顯示鼠耳芥(Arabidopsis thaliana)硫氧還蛋白還原酶-接頭-硫氧還蛋白合成融合物的胺基酸序列(Arab TR-link-Trxh；SEQ ID NO37)與麻風分枝桿菌硫氧還蛋白還原酶-硫氧還蛋白天然融合物(M.lepTR/Trxh；SEQ ID NO36)的clustal比對。整體上，這兩種蛋白質在胺基酸水平上有大約50％的一致性。
圖4是柱型圖，顯示針對各種轉基因鼠耳芥屬植物種子級分測量到的硫氧還蛋白/硫氧還蛋白還原酶活性。以大腸桿菌硫氧還蛋白和硫氧還蛋白還原酶活性的百分數表示相對比活性。圖中編號的柱對應如下1.W.T.+油質蛋白-硫氧還蛋白2.W.T.+硫氧還蛋白-油質蛋白3.W.T.+硫氧還蛋白
4.W.T.+油質蛋白-硫氧還蛋白還原酶5.W.T.+硫氧還蛋白還原酶-油質蛋白6.W.T.+硫氧還蛋白還原酶7.硫氧還蛋白+油質蛋白-硫氧還蛋白還原酶8.硫氧還蛋白+硫氧還蛋白還原酶-油質蛋白9.硫氧還蛋白+硫氧還蛋白還原酶10.硫氧還蛋白還原酶+油質蛋白-硫氧還蛋白11.硫氧還蛋白還原酶+硫氧還蛋白-油質蛋白12.油質蛋白-M.lep TR/Trxh13.大腸桿菌硫氧還蛋白還原酶+硫氧還蛋白圖5提供了一系列可以用於本文所述異源多聚體融合蛋白和異源多聚體蛋白複合物中的示例性蛋白質。
發明詳述如前述，本發明涉及用於製備多聚體蛋白質，包括第一和第二重組多肽)、多聚體蛋白質複合物、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白多肽鏈、免疫球蛋白、氧還蛋白融合多肽和第一及第二硫氧還蛋白相關蛋白質的改良新方法；和相關產品。這些方法允許產生與油體結合的活性多聚體蛋白複合物。而與多聚體蛋白複合物結合的油體可以用於製備各種有用的乳劑。
因此，本文提供製備與油體結合的重組多聚體蛋白質複合物的方法，所述方法包括(a)在包含油體的細胞中產生第一重組多肽和第二重組多肽，其中所述第一重組多肽能夠與所述第二重組多肽在此細胞中結合形成所述多聚體蛋白複合物；和(b)通過能夠結合所述油體和所述第一重組多肽的油體靶向蛋白使所述多聚體蛋白質複合物與油體結合。
定義和術語除非另行定義，否則本文所用所有科學技術術語均採用本發明所屬領域技術人員通常理解的含義。在允許的情況下，在本文整個公開中提及的所有專利、申請、公開的申請和其它出版物以及來自GenBank、SwissPro和其它資料庫的序列都完整地併入作為參考。
本文中，短語「多聚體蛋白質複合物」是指兩個或多個多肽鏈持久地或重複地相互作用或相互配合形成包含此兩個或多個多肽鏈的生物學活性裝配物。應當注意的是，這些多肽無需相互作用或相互配合(coordination)形成複合物也可以獨立地具有生物學活性。多聚體蛋白質複合物可以提供生物學結構，或可能能夠有利於化學或生物學反應。例如，多聚體蛋白質複合物中的一個蛋白質區域可以重複激活或失活該多聚體蛋白質複合物中所含的另一個或多個蛋白質的生物學或代謝活性。在一個實施方案中，多聚體蛋白質複合物中所含的第一和第二重組多肽可以以獨立的非連續多肽鏈形式結合或相互作用，或多聚體蛋白質複合物可以以第一和第二重組多肽之間的融合多肽(多聚體融合蛋白)的形式製備。
本文所述多聚體蛋白質複合物的兩個或多個多肽之間的重複的(例如，反覆發生的)相互作用或結合(association)的一個例子是兩個或多個不同的氧還蛋白之間的相互作用以形成異源多聚體蛋白質複合物。在此方面使用的示例性氧還蛋白有硫氧還蛋白和硫氧還蛋白還原酶。再一個例子是兩個或多個免疫球蛋白多肽鏈相互作用形成免疫球蛋白。本文中，短語「異源多聚體蛋白質複合物」是指兩個或多個不同的多肽鏈持久地或重複地相互作用或相互配合形成包含此兩個或多個多肽鏈的生物活性裝配物。本文提供的多聚體蛋白質複合物的其它實例包括第一及第二重組多肽、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、第一及第二免疫球蛋白多肽鏈、氧還蛋白融合多肽、和第一及第二硫氧還蛋白相關蛋白。
所述重組多肽或多聚體蛋白質複合物與油體結合。本文中，短語「油體」是指任何細胞類型中的任何油或脂肪貯存細胞器。因此，油體可以從包含油體的任何細胞中獲得，包括植物細胞(例如，其描述見Huang(1992)Ann.Rev.Plant Mol.Biol.43177-200)，動物細胞(見例如Murphy(1990)Prog Lipid Res 29(4)299-324)，包括脂肪細胞、肝細胞、產類固醇的細胞、乳腺表皮細胞、巨噬細胞，藻類細胞(見例如Rossler(1988)J.Physiol.London，24394-400)，真菌細胞包括酵母細胞(見例如Leber等(1994)Yeast 101421-1428)和細菌細胞(見例如Pieper-Furst等(1994)J.Bacteriol.1764328-4337)。優選本文所用油體是可以從植物細胞中獲得的油體，更優選是可以從植物種子細胞中獲得的油體。
本文中，短語「能夠結合」、「結合(associate)」或其語法變體指兩個或多個多肽之間的任何相互作用，包括任何共價相互作用(例如，多聚體融合蛋白)以及非共價相互作用。示例性的非共價相互作用可以是油體靶向蛋白和氧還蛋白或免疫球蛋白多肽鏈之間，以及兩個或多個獨立的油體蛋白融合蛋白中包含的兩個或多個不同蛋白質(例如，油質蛋白-硫氧還蛋白和油質蛋白-硫氧還蛋白還原酶中的氧還蛋白)之間發生的非共價相互作用。
本文中，術語「重組」(也稱作異源)在重組蛋白和胺基酸的背景下是指「屬於不同自然來源」或是非自然狀態。例如，如果宿主細胞用來自另一生物體，尤其是來自另一物種的核苷酸序列轉化，則該核苷酸序列和其編碼的胺基酸序列相對該宿主細胞以及由此相對帶有此基因的宿主細胞的後代而言是重組的(異源的)。類似地，重組(或異源)也是指來源於並插入在相同天然原始細胞類型中的核苷酸序列，但該序列以非天然狀態存在，如不同的拷貝數或處於不同調控元件的控制下。轉化的核苷酸序列可以包括重組編碼序列或重組調節元件。或者，轉化的核苷酸序列可以完全是異源的，或可以包括異源和同源核酸序列的任何可能組合。
在本發明的各種實施方案中，第一和/或第二重組多肽、多聚體蛋白質複合物、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽和/或硫氧還蛋白相關蛋白在包含油體的細胞中產生。本文中，短語「在細胞中」、「在此細胞中」或其語法變體是指第一和/或第二重組多肽、多聚體蛋白質複合物、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽和/或硫氧還蛋白相關蛋白可以在該細胞的任何細胞區室中產生，只要該細胞包含油體即可。在使用植物細胞的本發明實施方案中，此短語意在包括植物的質外體。
在本文提供的多種實施方案中，第一和/或第二重組多肽、多聚體蛋白質複合物、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽和/或硫氧還蛋白相關蛋白通過油體靶向蛋白與油體結合。本文中，短語「油體靶向蛋白」是指能夠與油體結合的任何蛋白質、蛋白質片斷或多肽。可用於本文中的油體靶向蛋白的例子包括油體蛋白，如油質蛋白和caleosin；免疫球蛋白，如雙特異性抗體；等。
在本文所述使用油體蛋白的實施方案中，第一和/或第二重組多肽、多聚體蛋白質複合物、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽和/或硫氧還蛋白相關蛋白優選與油體蛋白融合。術語「油體蛋白」是指天然存在於細胞中能夠與油體結合的任何蛋白質，包括任何油質蛋白或caleosin。
因此，本文提供了在細胞中表達包含第一和第二重組多肽的重組多聚體蛋白質複合物的方法，所述方法包括(a)向細胞中引入包含如下成分的第一嵌合核酸序列(i)在所述細胞中能夠調節轉錄的第一核酸序列；(ii)與第一核酸序列可操作連接的、編碼與油體蛋白融合的第一重組多肽的第二核酸序列，所述第一重組多肽的例子是氧還蛋白、免疫球蛋白多肽鏈或硫氧還蛋白相關蛋白；(b)向所述細胞中引入包含如下成分的第二嵌合核酸序列(i)能夠在所述細胞中調節轉錄的第三核酸序列；(ii)與第三核酸序列可操作連接的、編碼第二重組多肽的第四核酸序列，所述第二重組多肽的例子是第二氧還蛋白、第二免疫球蛋白多肽鏈或第二硫氧還蛋白相關蛋白；(c)在允許所述第一和第二重組多肽在包含油體的子代細胞中表達的條件下培養所述細胞，其中所述第一重組多肽和所述第二重組多肽能夠，優選在所述子代細胞中，形成多聚體蛋白質複合物；和(d)通過所述油體蛋白使所述第一重組多肽和油體結合。
術語「核酸」在本文中是指由天然鹼基、糖和糖間(主鏈)鍵組成的核苷酸或核苷單體的序列。此術語也包括包含功能類似的非天然單體或其部分的修飾的或替代的序列。核酸序列可以是核糖核酸(RNA)或脫氧核糖核酸(DNA)，並可以含有天然鹼基(包括腺嘌呤、鳥嘌呤、胞嘧啶、胸腺嘧啶和尿嘧啶)。序列也可以含有修飾鹼基，如黃嘌呤、次黃嘌呤、2-氨基腺嘌呤、6-甲基、2-丙基和其它烷基腺嘌呤、5-滷代尿嘧啶、5-滷代胞嘧啶、6-氮雜尿嘧啶、6-氮雜胞嘧啶和6-氮雜胸腺嘧啶、假尿嘧啶、4-硫代尿嘧啶、8-滷代腺嘌呤、8-氨基腺嘌呤、8-巰基腺嘌呤、8-硫代烷基腺嘌呤、8-羥基腺嘌呤和其它8-取代的腺嘌呤、8-滷代鳥嘌呤、8-氨基鳥嘌呤、8-巰基鳥嘌呤、8-硫代烷基鳥嘌呤、8-羥基鳥嘌呤和其它8-取代的鳥嘌呤、其它氮雜和脫氮雜尿嘧啶、胸腺嘧啶、胞嘧啶、腺嘌呤或鳥嘌呤、5-三氟甲基尿嘧啶和5-三氟胞嘧啶。
多聚體蛋白質複合物根據本文所述方法和組合物，能夠形成多聚體蛋白質複合物的任何兩個重組多肽均可以使用。編碼這兩個重組多肽的核酸序列可以從任何生物來源獲得，或可以合成製備。一般地，編碼多聚體蛋白質的核酸序列是本領域已知的並可以容易地獲得。可以使用已知的編碼多聚體蛋白質複合物的核酸序列設計並構建基於核酸序列的探針，以便發現和鑑定之前未發現的編碼多聚體蛋白質複合物的核酸序列，例如這可以通過篩選cDNA或基因組文庫或使用2-或多雜交系統來實現。由此，可以發現其它編碼多聚體蛋白質複合物的核酸序列並可以按本文所述使用這些序列。
包含在本文所述多聚體蛋白質複合物中的第一和/或第二重組多肽本身可以是異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽和/或第一和/或第二硫氧還蛋白相關蛋白的形式。
編碼第一和第二重組多肽、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽和/或第一和/或第二硫氧還蛋白相關蛋白的核酸序列可以從不同的來源獲得，或可以從相同的來源獲得。然而，一般該核酸序列獲自相同或相似生物來源。在編碼第一和第二重組多肽蛋白質的核酸序列獲自相同來源的某些實施方案中，編碼第一重組多肽和第二重組多肽的核酸序列可以是天然融合的。根據特定實施方案，編碼第一和第二重組多肽的核酸序列從植物來源獲得。
迴避油體表面的接頭本文中可以使用具有可變長度和/或負電荷的多肽間隔物或接頭將第一和/或第二重組多肽、多聚體蛋白質複合物、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽和第一和/或第二硫氧還蛋白相關蛋白與符合閱讀框的油體靶向蛋白分開，以提高多肽或複合物的活性和/或可接近性。例如，在本文所述的一個實施方案中，在編碼足夠的油體蛋白部分的核酸序列和編碼第一和/或第二重組多肽、多聚體蛋白質複合物、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽或第一和/或第二硫氧還蛋白相關蛋白的核酸序列之間，放置編碼迴避油體表面的接頭胺基酸序列的接頭核酸序列。
迴避油體表面的接頭被置於油體靶向蛋白和讀框內目的重組多肽，如本文所述多聚體蛋白質複合物之間，以使帶負電荷的油體表面和目的重組多肽間的距離增大和/或相互作用減少。帶負電荷的接頭被帶負電荷的油體表面排斥，這就使接頭所連接的重組多肽與油體表面的距離增大或相互作用減少。與油體表面的距離增加將導致重組多肽更易於接近，例如其靶標表面、蛋白質表面、蛋白質配偶體(partner)，並較少受到帶電荷的油體表面的影響。可以用於本文中的示例性接頭序列可以是帶負電荷的接頭或具有至少約35kd或更大分子量的接頭。
本文中，「帶負電荷的接頭」序列是指pI值小於或等於油體的pI值的任何胺基酸區段或編碼它的核酸。在某些實施方案中，帶負電荷的接頭的pI為在所用的特定植物和細胞體系中油體pI值的大約90％、80％、70％、60％、50％、40％、30％、低至約25％或更低。帶負電荷的接頭可以例如通過包含帶負電的胺基酸殘基的任何組合來製備。例如，在一個實施方案中，帶負電荷的接頭包含聚穀氨酸或聚天冬氨酸序列或這兩種胺基酸殘基的任何組合。此帶負電荷的接頭典型地長至少5、10、15、20、25、30、35、40、45、50、55、60、65、70、75、80、85、90、95、100或更多個胺基酸；並優選是非蛋白水解的(例如，非蛋白水解接頭)，不具有能有效蛋白水解的位點。當利用接頭的大小而非電荷來最小化目的重組多肽與油體表面的相互作用時，接頭是非蛋白水解的並且分子量為約35kd至多達約100kd。對此大小上限進行選擇是為了接頭不會顯著影響目的重組多肽的表達、活性、構象和/或與靶標的接近。
在使用非蛋白水解接頭胺基酸序列的本文所述某些實施方案中，基因融合物或蛋白質融合物(多聚體融合蛋白)還可以任選地包含編碼能夠被酶或化學物質特異切割的序列的接頭核酸或胺基酸序列，其中此接頭序列位於非蛋白水解接頭序列和編碼期望的重組蛋白質區域(如本文所述第一和/或第二重組多肽、多聚體蛋白複合物、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽或第一和/或第二硫氧還蛋白相關蛋白)的序列之間。當本文使用可切割接頭序列時，在特定的實施方案中，其比非蛋白水解接頭序列位於融合蛋白的油體靶向蛋白區域的更下遊。藉助可切割接頭，本文所述重組融合多肽，如多聚體融合蛋白和氧還蛋白融合多肽可以通過引入能夠切割所述多聚體融合蛋白和/或氧還蛋白融合多肽的酶或化學物質與所述油體分離並得以純化，由此得到和/或分離到此期望蛋白質。本文考慮到，在使用本文所述方法分離或純化蛋白質時，在非蛋白水解接頭/間隔序列下遊使用可切割接頭序列將提高蛋白質的回收率。
可以對編碼第一或第二重組多肽的核酸序列進行改變，例如根據所選用於表達此第一和第二重組多肽的具體細胞類型的優選密碼子使用優化此核酸序列，或改變已知會造成mRNA不穩定的基序，以提高表達水平(見例如PCT專利申請97/02352)。比較第一和第二重組多肽的密碼子使用和宿主密碼子使用將能夠鑑定到可作改變的密碼子。例如，典型地，植物進化趨向於優選富含CG的核苷酸序列，而細菌進化導致對富含AT的核苷酸序列的偏好。通過修飾核酸序列將宿主細胞優選的核酸序列摻入其中，可以優化表達。通過改變密碼子使用構建合成基因的例子可參見PCT專利申請93/07278。可以使用定向誘變、隨機誘變(Shiraishi等(1998)Arch.Biochem.Biophys.358104-115；Galkin等(1997)Protein Eng.10687-690；Carugo等(1997)Proteins 2810-28；Hurley等(1996)Biochemistry 35；5670-5678)、基因改組和/或通過添加有機溶劑(Holmberg等(1999)Protein Eng.12851-856)，改變第一和第二重組多肽。可以以類似方式改變用於本文所述方法和產品中的任何多肽間隔物。
在本文給出的特定實施方案中，能夠形成多聚體蛋白質複合物的重組多肽或硫氧還蛋白相關蛋白能夠形成異源多聚體蛋白質複合物。使用本文所述方法能夠與油體結合產生的、含有彼此能重複相互作用以達到激活、失活、氧化、還原、穩定等作用的多肽鏈的示例性異源多聚體蛋白質複合物包括圖5中給出的那些。因此，本文提供的用於異源多聚體蛋白質複合物中的示例性蛋白質和編碼它的核酸構建體，除了此處描述的外，還包括圖5中給出的那些。
可以用於本文所述的第一和/或第二重組多肽、多聚體蛋白質複合物、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽或第一和/或第二硫氧還蛋白相關蛋白中的其它多肽區域尤其包括表1中給出的那些免疫球蛋白區域。
表1-抗體異二聚體

如上述，在一個實施方案中，本文所述示例性異源多聚體蛋白質複合物和示例性異源多聚體融合蛋白包含氧還蛋白，如硫氧還蛋白和硫氧還蛋白還原酶和免疫球蛋白。
油體靶向蛋白編碼可以用於本文所述方法和組合物中的油體靶向蛋白的核酸序列可以是編碼能夠與第一重組多肽、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽和/或第一和/或第二硫氧還蛋白相關蛋白和油體結合的油體靶向蛋白質、蛋白質片斷或肽的任何核酸序列。編碼油體靶向肽的核酸序列可以通過合成或從任何生物來源獲得。
例如，在一個實施方案中，油體靶向蛋白是免疫球蛋白或免疫球蛋白衍生分子，例如，雙特異性單鏈抗體。單鏈抗體和雙特異性單鏈抗體的製備是本領域已知的(見例如，US專利US 5,763,733、US 5,767,260和US 5,260,203)。編碼可充當油體靶向蛋白的單鏈抗體的核酸序列可以從表達抗油質蛋白的單克隆抗體的雜交瘤細胞系中製得，參見Alting-Mees等(2000)IBC抗體工程國際年會，Poster#1。為了獲得對第一重組多肽的特異性，從抗第一重組多肽產生的單克隆中製備第二單鏈抗體編碼核酸序列並使其與抗油質蛋白單鏈抗體連接。在此實施方案中，油體通過油體靶向蛋白和第一重組多肽及油體的非共價相互作用而實現與第一重組多肽的結合。或者，可以將第一重組多肽製備為與油體靶向蛋白的融合蛋白。例如，可以使編碼抗油質蛋白單鏈抗體的核酸序列與編碼第一重組多肽的核酸序列融合。
以非免疫球蛋白為基礎的能夠與第一重組多肽結合的油體靶向蛋白可以使用例如噬菌體展示文庫技術(Pharmacia Biotech CatalogueNumber 27-9401-011重組噬菌體抗體系統表達試劑盒)開發和製備。
還可以對油體靶向蛋白進行化學修飾。例如，可以使用化學試劑如生物素基-N-羥基琥珀醯亞胺酯改變賴氨酸殘基的化學修飾實現稱作生物素化的過程，以修飾油質蛋白。方便地，這可以通過體外生物素化油體來實現。而體內生物素化可以通過大腸桿菌乙醯基-CoA羧化酶的生物素羧基載體蛋白的生物素化域肽來進行(Smith等(1998)Nucl.Acids Res.261414-1420)。可以隨後使用親和素或鏈黴親和素以實現氧還蛋白與油體的結合。
在特定實施方案中，油體靶向蛋白是油體蛋白，例如油質蛋白或caleosin或來源於它們的能夠靶向油體的足夠部分。編碼油質蛋白的核酸序列是本領域已知的。這些包括例如鼠耳芥屬油質蛋白(van Rooijen等(1991)Plant Mol.Bio.181177-1179)；玉米油質蛋白(Qu和Huang(1990)J.Biol.Chem.Vol.265 42238-2243)；菜籽油菜油質蛋白(Lee和Huang(1991)Plant Physiol.961395-1397)；和胡蘿蔔油質蛋白(Hatzopoulos等(1990)Plant Cell Vol.2，457-467)。caleosin核酸序列也是本領域已知的(Naested等(2000)Plant Mol.Biol.44(4)463-476；Chen等(1999)Plant Cell Physiol.40(10)1079-1086)。可以用於本發明中的來源於動物細胞的油體蛋白包括adopihilin(Brasaemle等，(1997)J.Lipid Res.，382249-2263；Heid等(1998)Cell Tissue Research 294309-321)、perilipin(Blanchette-Mackie等，(1995)J.Lipid Res.36；1211-1226；Servetnick等(1995)J.Biol.chem..27016970-16973)、載脂蛋白如apo A-I、A-II、A-IV、C-I、C-II、CIII(Segrest等(1990)Proteins 8103-117)和apoB(Chatterton等(1995)J.Lipid Res.362027-2037；Davis，RA inVance DE，Vance J.編，脂蛋白結構和分泌，The Nethelands，Elsevier，191403-426)。
在一個實施方案中，第一重組多肽與油體蛋白融合。方法學進一步參見US專利5,560,554，特此將其完整地併入此處作為參考。可以將第一重組多肽與油體蛋白的N端及C端融合(見Moloney和van Rooijen(1996)INFORM 7107-113)並可以使用油體蛋白片斷如油質蛋白分子的中心域，或修飾版本的油體蛋白。在此實施方案中，第二重組多肽在細胞內表達，然後在細胞內與第一重組多肽結合在細胞內形成多聚體蛋白質複合物。然後可以方便地從細胞中分離出包含多聚體蛋白質複合物的油體。
在再一實施方案中，第一和第二重組多肽分別與油體蛋白融合。在此實施方案中，編碼第一和第二多肽的核酸序列可以單獨地製備並引入不同的細胞系中，或可以將它們引入相同的細胞系中。當核酸序列被引入相同細胞系時，可以使用兩個獨立的表達載體製備這些核酸序列，或可以使用一個載體製備它們，在此載體中包含了編碼與油體蛋白融合的第一多肽和與油體蛋白融合的第二多肽的核酸序列。當使用不同細胞系時，通過子代的隨後交配(例如植物交配)製備包含如下油體的細胞世代，其中所述油體包含與油體蛋白融合的第一及第二重組多肽。
在備選實施方案中，第一和第二重組多肽相融合形成包含多聚體蛋白質複合物的多聚體融合蛋白。在此實施方案中，第一和第二多肽通過能夠與此融合蛋白並與油體結合的油體靶向蛋白與油體結合。在特定實施方案中，包含多聚體蛋白複合物的融合蛋白與油體蛋白如油質蛋白或caleosin融合。
在本文提供的多聚體蛋白質複合物是免疫球蛋白(例如多聚體免疫球蛋白複合物)的實施方案中，尤其優選的油體靶向蛋白是與免疫球蛋白結合蛋白如A蛋白(US專利5,151,350)、L蛋白(US專利5,965,390)和G蛋白(US專利4,954,618)或該免疫球蛋白結合蛋白的活性片斷結合的油質蛋白或caleosin。
可以通過例如製備油體(進一步詳細描述見下)和利用如SDS凝膠電泳鑑定這些製品中的蛋白，發現新的油體蛋白。可以針對這些蛋白質產生多克隆抗體用於篩選cDNA文庫以鑑定編碼油體蛋白的核酸序列。此方法學是本領域技術人員熟悉的(Huynh等(1985)《DNA Cloning》第1卷，a Practical Approach ed.DM Glover，IRL Press，pp 49-78)。還可以使用編碼油體蛋白的已知核酸序列(例如鼠耳芥屬、菜籽油菜(rapeseed)、胡蘿蔔和玉米的該核酸序列)探測例如cDNA和基因組文庫尋找編碼油體蛋白的核酸序列的存在來發現新的油體蛋白。
在一個實施方案中，第一和第二多肽是第一和第二氧還蛋白。因此，本文提供的一個實施方案涉及製備氧還蛋白的改良新方法。令人意外的是發現，與油體相結合製備時，和第二氧還蛋白以融合蛋白的形式製備的氧還蛋白具有完全的酶學活性。相反，當在缺少第二氧還蛋白的情況下製備該氧還蛋白時，該氧還蛋白具有降低的酶學活性。在一個實施方案中，第一氧還蛋白以氧還蛋白融合多肽的形式製備時比以非融合多肽的形式製備時活性高至少5倍。
因此，本文提供了製備與異源多聚體氧還蛋白複合物結合的油體的方法，所述方法包括(a)在包含油體的細胞中製備第一氧還蛋白和第二氧還蛋白，其中所述第一氧還蛋白能與所述第二氧還蛋白(優選在細胞中)相互作用形成所述異源多聚體氧還蛋白複合物；和(b)通過能夠與所述油體及所述異源多聚體氧還蛋白複合物結合的油體靶向蛋白使所述異源多聚體氧還蛋白複合物與油體結合。
在一個特定的實施方案中，第一和第二氧還蛋白以融合蛋白的形式製備形成氧還蛋白融合多肽。因此，本文提供製備與油體結合的具有酶學活性的氧還蛋白的方法，包括a)在細胞中製備包含相連接的第一氧還蛋白和第二氧還蛋白的氧還蛋白融合多肽；b)通過能夠與所述氧還蛋白融合多肽及所述油體結合的油體靶向蛋白使所述氧還蛋白融合多肽與油體結合；和c)分離與所述氧還蛋白融合多肽結合的所述油體。此與氧還蛋白結合的油體可以用於製備多種有用的乳劑。
本文中，短語「氧還蛋白」或其語法變體是指能夠參與電子傳遞的任何蛋白質或活性蛋白質片斷。例如，氧還蛋白能夠催化電子從電子供體(也常常稱作還原劑)轉移至電子受體(也常常稱作氧化劑)上。在電子轉移過程中，還原劑(電子供體)被氧化，而氧化劑(電子受體)被還原。用於此處的示例性氧還蛋白包括鐵-硫蛋白、細胞色素、具氧化還原活性的巰基蛋白、具氧化還原活性的黃素蛋白。為了執行其作為電子導體的功能，已知氧還蛋白如硫氧還蛋白和硫氧還蛋白還原酶通過在多聚體蛋白質複合物(例如異源多聚體蛋白質複合物)中彼此相互作用或結合來發揮作用。
術語「氧還蛋白融合多肽」在本文中是指包含與第二氧還蛋白連接的第一氧還蛋白的任何融合多肽(如讀框內翻譯融合物)。可以用於本發明方法和組合物中的氧還蛋白可以是任何氧還蛋白。在一個實施方案中，第一和第二氧還蛋白是天然一般共同來自相同來源的一對氧還蛋白。在一個特定實施方案中，第一氧還蛋白是硫氧還蛋白而第二氧還蛋白是硫氧還蛋白還原酶。
氧還蛋白融合多肽可以在包含油體的任何細胞，包括任何動物細胞、植物細胞、藻類細胞、真菌細胞或細菌細胞中產生。在某些實施方案中，在植物細胞中製備氧還蛋白融合多肽，在特定實施方案中，在種子植物的種子細胞中製備氧還蛋白。
在特定實施方案中，所用油體靶向蛋白是油體蛋白。在使用油體蛋白的本發明實施方案中，第一和第二氧還蛋白優選與油體蛋白共價融合。因此，本發明提供了製備與油體結合的氧還蛋白的方法，包括a)向細胞中引入包含如下成分的嵌合核酸序列1)能夠在所述細胞中調節轉錄的第一核酸序列；2)與1)可操作連接的編碼重組融合多肽的第二核酸序列，所述重組融合多肽包含(i)編碼足以使所述重組融合多肽靶向油體的油體蛋白部分的第一核酸序列和與之在閱讀框中連接的(ii)編碼包含相連接的第一氧還蛋白和第二氧還蛋白的氧還蛋白融合多肽的第二核酸序列；3)與2)可操作連接的能夠在所述細胞中終止轉錄的第三核酸序列；
b)在允許所述氧還蛋白融合多肽在包含油體的子代細胞中表達的條件下培養所述細胞；c)從所述子代細胞中分離包含所述氧還蛋白融合多肽的所述油體。
氧還蛋白根據本文提供的各種方法和組合物，可以使用編碼氧還蛋白的任何核酸序列。編碼第一和/或第二氧還蛋白的核酸序列可以從任何生物來源獲得或可以合成製備。一般地，編碼氧還蛋白的核酸序列是本領域熟知的且易於獲得。見，例如Cristiano等(1993)Genomics 17(2)348-354；Doyama等(1998)Plant Sci.13753-62；Hoeoeg等(1984)Biosci.Rep.4917-923；以及表5給出的Swiss蛋白質序列。可以使用編碼氧還蛋白的已知核酸序列設計並構建基於核酸序列的探針以開發和鑑定先前未知的編碼氧還蛋白的核酸序列，例如可以通過篩選cDNA或基因組文庫來實現。因此，可以開發其它的核酸序列用於本發明。
編碼第一和/或第二氧還蛋白的核酸序列可以從不同來源或從相同來源獲得。然而，一般編碼氧還蛋白融合多肽的核酸序列包含來自相同或相似生物來源的編碼第一和第二氧還蛋白的核酸序列。在本文提供的某些實施方案中，當第一和第二氧還蛋白的核酸序列來自相同來源時，編碼第一氧還蛋白和第二氧還蛋白的核酸序列可以是天然融合的。根據一個特定的實施方案，編碼第一和第二氧還蛋白的核酸序列優選從植物來源獲得。
如上述，可以使用具有可變長度的多肽間隔物或接頭將第一和第二氧還蛋白彼此和/或與油體靶向蛋白分開；並且可以使第一和/或第二氧還蛋白與其它的氧還蛋白(例如一個或多個)融合。
可以改變編碼氧還蛋白的核酸序列，例如根據所選用於表達該氧還蛋白的具體細胞類型的優選密碼子使用優化此核酸序列，或改變已知會導致mRNA不穩定的基序，以提高表達水平(見例如PCT轉錄申請97/02352)。對氧還蛋白的密碼子使用和宿主的密碼子使用進行比較，將能夠鑑定出可作改變的密碼子。例如，典型地，植物進化趨向於優選富含CG的核苷酸序列，而細菌進化導致對富含AT的核苷酸序列的偏好。通過修飾核酸序列將宿主細胞優選的核酸序列摻入其中，可以優化表達。通過改變密碼子使用構建合成基因的例子可參見PCT專利申請93/07278。可以使用定向誘變、隨機誘變(Shiraishi等(1998)Arch.Biochem.Biophys.358104-115；Galkin等(1997)Protein Eng.10687-690；Carugo等(1997)Proteins 2810-28；Hurley等(1996)Biochemistry 35；5670-5678)和/或通過添加有機溶劑(Holmberg等(1999)Protein Eng.12851-856)，改變氧還蛋白。可以以類似方式改變第一和第二氧還蛋白之間的任何多肽間隔物。
可以通過開發二維矩陣和使用例如比色還原測定(colorometricreduction assay)(Johnson等(1984)J of Bact.Vol.158 31061-1069，Luthman等(1982)Biochemistry vol 21 266628-2233)確定哪種第一和第二氧還蛋白組合在電子傳遞中最有效來選擇第一和第二氧還蛋白。可以通過體外測定小麥貯存蛋白和奶貯存蛋白β-乳球蛋白的還原(Del Val等(1999)J.Allerg.Clin.Immunol.103690-697)，測試硫氧還蛋白和硫氧還蛋白還原酶的各組合。使用相同的策略，可以評價第一和第二氧還蛋白之間的多肽間隔物的有效性。
可以用於本發明中的第一和第二氧還蛋白包括但不限於選自如下氧還蛋白的任何第一氧還蛋白和第二氧還蛋白細胞色素如細胞色素a、細胞色素b和細胞色素c；含有卟啉的蛋白質如血紅蛋白；鐵硫蛋白，如鐵氧還蛋白；黃素蛋白如硫氧還蛋白還原酶、NADH脫氫酶、琥珀酸脫氫酶、二氫硫辛酸脫氫酶、醯基-CoA脫氫酶、D-胺基酸氧化酶、黃嘌呤氧化酶、乳清酸還原酶和醛氧化酶；連接吡啶的脫氫酶，例如乳酸脫氫酶、甘油醛-3-磷酸脫氫酶、蘋果酸脫氫酶和β-羥基butarate脫氫酶；和具有氧化還原活性的含巰基蛋白質如硫氧還蛋白。
在某些實施方案中，本文提供的氧還蛋白是硫氧還蛋白和其還原劑硫氧還蛋白還原酶(其共同又稱作「硫氧還蛋白相關」蛋白質)。本文中，術語「硫氧還蛋白」是指屬於通過二硫鍵的形成或水解催化氧化還原的巰基轉移酶家族的相對小的蛋白質(典型地大約12kDa)，所述巰基轉移酶即使不是普遍也是廣泛地分布在整個動植物和細菌界。硫氧還蛋白的此還原形式是還原甚至最難處理的二硫鍵的一個極好的催化劑。為了還原氧化的硫氧還蛋白，兩個細胞還原劑提供了還原當量(reductionequivalents)還原的鐵氧還蛋白和NADPH。這些還原當量通過與不同硫氧還蛋白還原酶(包括NADPH硫氧還蛋白還原酶和鐵氧還蛋白硫氧還蛋白還原酶)相互作用或結合提供給硫氧還蛋白。提供這些還原當量需要形成包含硫氧還蛋白和硫氧還蛋白還原酶的異源多聚體蛋白質複合物。鐵氧還蛋白硫氧還蛋白還原酶參與稱作Trxf和Trxm的植物硫氧還蛋白的還原，兩者均參與葉綠體中光合作用的調節。在植物種子中具有活性的NADPH/硫氧還蛋白稱作Trxh(本文中也稱作h型硫氧還蛋白)，其能夠還原多種的蛋白質，由此起到重要細胞氧化還原緩衝劑的作用。一般地，在細菌或動物細胞中僅發現一類硫氧還蛋白，其與植物Trxh型類似。h型硫氧還蛋白能夠被NADPH和NADPH-硫氧還蛋白還原酶還原。
示例性硫氧還蛋白的其它特徵為其是具有4至6個α螺旋圍繞的5個β片層核心的蛋白質。示例性硫氧還蛋白還可以表徵為具有含有如下共有胺基酸序列的活性位點X C Y Y C Z，其中Y是任何胺基酸如疏水或非極性胺基酸，其中X可以是20種胺基酸中的任一種，優選疏水胺基酸如色氨酸，而Z可以是任何胺基酸，優選極性胺基酸。
在某些實施方案中，本文所用硫氧還蛋白包含具有胺基酸序列XCGPCZ的活性位點。
當硫氧還蛋白或硫氧還蛋白樣蛋白質的活性位點中的半胱氨酸被氧化後，它們形成分子內二硫鍵。在還原狀態下，同樣的活性位點能夠通過可逆氧化其活性位點的雙巰基為二硫鍵參與氧化還原反應並催化二巰基二硫鍵交換反應。
示例性硫氧還蛋白是本領域熟知的，可以從包括鼠耳芥(RiveiraMadrid等(1995)Proc.Natl.Acad.Sci.925620-5624)、小麥(Gautier等(1998)Eur.J.Biochem.252314-324)；大腸桿菌(Hoeoeg等(1984)Biosci.Rep.4917-923)和嗜熱微生物如Methanococcusjannaschii和Archaeoglobus fulgidus(PCT專利申請00/36126)的幾種生物體中獲得。硫氧還蛋白也已在幾種宿主系統中重組表達，包括細菌(Gautier等(1998)Eur.J.Biochem.252314-324)和植物(PCT專利申請WO 00/58453)。大腸桿菌來源的硫氧還蛋白的商業製品可以容易地從例如Sigma Cat No.T 0910硫氧還蛋白(大腸桿菌，重組體；大腸桿菌中表達)獲得。
編碼本文所述硫氧還蛋白多肽的示例性核酸序列可以容易地從多種不同生物學來源獲得，包括大腸桿菌(Hoeoeg等(1984)Biosci.Rep.4917-923)；Methanococcus jannaschii和Archaeoglobus fulgidus(PCT專利申請00/36126)；鼠耳芥(Rivera-Madrid(1995)Proc.Natl.Acad.Sci.92；5620-5624)；小麥(Gautier等(1995)Eur.J.Biochem.252(2)314-324)；菸草(Marty等(1991)Plant Mol.Biol.17143-148)；大麥(PCT專利申請00/58352)；水稻(Ishiwatari等(1995)Planta 195456-463)；大豆(Shi等(1996)Plant Mol.Biol.32653-662)；菜籽油菜(Bower等，Plant Cell 81641-1650)和小牛(Terashima等(1999)DNA Seq.10(3)；203-205)等。在其它實施方案中，本文所用核酸的例子包括編碼SEQ ID NOs38、42、46和50給出的硫氧還蛋白和硫氧還蛋白樣多0肽鏈的那些；和編碼表5中SEQ ID NOs52-194給出的硫氧還蛋白和硫氧還蛋白樣多肽鏈的那些。編碼SEQ ID NOs52-194所示胺基酸的各核酸序列可以通過表5(括號中)中給出的Swiss蛋白質標識(登錄)號容易地鑑定。
本文中，術語「硫氧還蛋白還原酶」是指與黃素如FAD複合的蛋白質。黃素化合物充當供給硫氧還蛋白還原酶蛋白質活性位點的電子供體。硫氧還蛋白還原酶具有能還原硫氧還蛋白的具有氧化還原活性的二硫鍵位點。硫氧還蛋白還原酶的活性位點含有2個半胱氨酸。圍繞形成活性位點的2個半胱氨酸殘基的胺基酸的類型可以在疏水、非極性或極性之間變動。硫氧還蛋白還原酶的例子是NADPH-硫氧還蛋白還原酶(NTR)，其是一般包含300-500個胺基酸的胞質同二聚體酶。大腸桿菌和植物硫氧還蛋白還原酶的晶體結構已經獲得(Waksman等(1994)J.Mol.Biol.236；800-816；Dai等(1996)J.Mol.Biol.263；1044-1057)。NADPH-硫氧還蛋白還原酶已經在異源宿主中進行過表達，例如，已在大腸桿菌(Jacquot等(1994)J.Mol.Biol.2351357-1363)和小麥(PCT專利申請00/58453)中表達鼠耳芥屬NADPH-硫氧還蛋白還原酶。
編碼硫氧還蛋白還原酶蛋白質的示例性核酸序列可以容易地從各種來源，如從圖5給出的序列和本文提供的序列表中，從鼠耳芥屬(RiveiraMadrid等(1995)Proc.Natl.Acad.Sci.USA 925620-5624)、大腸桿菌(Russel等(1988)J.Biol.Chem.2639015-9019)、大麥(PCT專利申請00/58352)和小麥(Gautier等(1998)Eur.J.Biochem.252314-324)等中獲得。在再其它實施方案中，本文所用示例性核酸包括編碼SEQ ID NOs8、9、10、40、44、48和50所示硫氧還蛋白還原酶多肽鏈的那些；和編碼表5中SEQ ID NOs195-313所示硫氧還蛋白還原酶多肽鏈的那些。編碼SEQ ID NOs195-313所示胺基酸的各核酸序列可以容易地通過圖5(括號中)提供的Swiss蛋白質標識(登錄)號鑑定。
還可以考慮用於本文所示方法和組合物中的是與本文所給硫氧還蛋白及硫氧還蛋白還原酶核酸和胺基酸「基本上同源」的核酸和胺基酸同系物(homolog)，這包括在低、中或高嚴緊性下與編碼本文所給硫氧還蛋白及硫氧還蛋白還原酶的核酸和胺基酸(例如實施例中、序列表中和/或表5中給出的那些)的核苷酸序列雜交的核苷酸序列所編碼的硫氧還蛋白和硫氧還蛋白還原酶多肽。本文中，DNA或核酸同系物是指包括預先選定的保守核苷酸序列，如編碼治療多肽的序列的核酸。術語「基本上同源」是指具有至少80％、優選至少90％、最優選至少95％同源性或較少百分數的同源性或一致性和保守的生物學活性或功能。
術語「同源性」或「一致性」常常可互換使用。在此方面，同源性或一致性百分數可以例如通過使用GAP電腦程式比較序列信息確定。GAP程序利用Needleman和Wunsch的比對方法(J.Mol.Biol.48；443(1970)，由Smith和Waterman修訂(Adv.Appl.Math.2；482(1981))。簡而言之，GAP程序將相似性確定為相似比對符號(即核苷酸或胺基酸)的數目除以兩個序列中較短者的符號總數目。GAP程序的優選默認參數可以包括(1)一元比較矩陣(含有值1(針對一致)和0(針對不一致))和Gribsko Burgess的權重比較矩陣(Nucl.Acids.Res.14；6745(1986)，描述見Schwartz和Dayhoff編《蛋白質序列和結構地圖集》NationalBiomedical Research Foundation，pp 353-358(1979))；(2)針對每個缺口(gap)的3.0罰分和對於每個缺口中的每個符號的額外0.10罰分；和(3)對於末端缺口無罰分。
對於序列一致性，由標準比對算法程序可以確定保守胺基酸數目，並且該數目可以與各供應商確立的默認缺口罰分一起使用。基本上同源的核酸分子一般可以在中等嚴緊性或高嚴緊性下沿目的核酸的全長雜交。優選地，兩個分子在高嚴緊性雜交。也考慮在雜交的核酸分子中將密碼子置換為簡併密碼子的核酸分子。
可以使用已知計算機算法如「FAST A」程序和例如Pearson和Lipman(Proc.Natl.Acad.Sci.USA 852444(1988))中的默認參數，確定任意兩個核酸分子是否具有至少80％、85％、90％、95％、96％、97％、98％或99％「一致性」的核苷酸序列。或者，可以使用國力生物技術信息資料庫中心的BLAST函數確定相對序列一致性。
一般地，對比序列以便獲得最大級別的匹配。「一致性」本身具有本領域公認的意義，可以使用公布的技術計算。(見例如ComputationalMolecular Biology，Lesk，A.M.編，Oxford University Press，紐約，1988；BiocomputingInformatics and Genome Projects，Smith D.W.編，Academic Press，紐約，1993；Computer Ahalysis of Sequence Data，Part I，Griffin，A.M.和Griffin，H.G.編，Humana Press，New Jersey，1994；Sequence Analysis in Molecular Biology，von Heinje，G..Academic Press，1987；和Sequence Ahalysis Primer，Gribskov，M.和Devereux，J.編，M Stockton Press，紐約，1991)。儘管存在多種方法可以測量兩個多核苷酸或多肽序列之間的一致性，術語「一致性」是本領域技術人員熟知(Carillo，H.Lipton，D.，SIAM J Applied Math481073(1988))。一般用於確定兩個序列之間的一致性或相似性的方法包括，但不限於，記載在Guide to Huge Computers，Martin J.Bishop編Academic Press，San Diego，1994和Carillo，H.Lipton，D.，SIAMJ Applied Math 481073(1988)中的那些。確定一致性和相似性的方法編在電腦程式中。用於確定兩個序列之間的一致性和相似性的優選電腦程式方法包括，但不限於，GCG程序包(Devereux，J.等，NucleicAcids Research 12(1)387(1984))、BLASTP、BLASTN、FASTA(Atshul，S.F.等，J Molec Biol.215403(1990))。
因此，本文中，術語「一致性」是指測試和參考多肽或多核苷酸之間的比較。例如，測試多肽可以被定義為與參考多肽90％或更多一致性的任何多肽。
本文中，術語至少「90％一致性」是指相對參考多肽90-99.99％的一致性。90％或更大水平上的一致性意味著如下事實如果為了舉例說明的目的假定比較長度100個胺基酸的測試和參考多核苷酸時，測試多肽中有不超過10％(即，100個中10個)的胺基酸與參考多肽的不同。可以在測試和參考多核苷酸之間進行類似比較。這樣的差異可以表現為隨機分布在整個長度的胺基酸序列中的點突變，或它們可以簇集在一個或多個不超過最大許可(如10/100)胺基酸差異(大約90％一致性)的各種長度的位點中。可以將差異定義為核酸或胺基酸替代或缺失。
本文中，在確定錯配百分數時的雜交嚴緊性如下1)高嚴緊性0.1×SSPE，0.1％SDS，65℃2)中嚴緊性0.2×SSPE，0.1％SDS，50℃3)低嚴緊性1.0×SSPE，0.1％SDS，50℃本領域技術人員知道為了得到穩定雜合體可以用洗滌步驟來選擇，並知道SSPE的組成(見例如，Sambrook，E.F.，Fritsch，T.Maniatis，分子克隆實驗室手冊(Molecular Cloning，A Laboratory Manual)，ColdSpring Harbor Laboratory Press(1989)，第3卷，p.B.13；也見描述通用實驗室溶液的各種目錄冊)。SSPE是pH7.4磷酸鹽緩衝的0.18NaCl。再有，本領域技術人員明了，雜合體的穩定性可以通過Tm確定，Tm是鈉離子濃度和溫度的函數(Tm＝81.5℃-16.6(log10[Na+])+0.41(％G+C)-600/l))，以致洗滌條件中對雜合體穩定性關鍵的唯一參數是SSPE(或SSC)中的鈉離子濃度和溫度。
應當理解，可以使用其它的緩衝液、鹽和溫度獲得等價嚴緊性。例如但不限於，使用低嚴緊性條件的方法如下(也參見Shilo和Weinberg，Proc.Natl.Acad.Sci.USA 786789-6792(1981))將含有DNA的濾膜預先在40℃於含有35％甲醯胺、5×SSC、50mM Tris-HCl(pH 7.5)、5mM EDTA、0.1％PVP、0.1％Ficoll、1％BSA和500μg/ml變性鮭精DNA(10×SSC是1.5M氯化鈉和0.15M檸檬酸鈉，調節至pH7)的溶液中處理6小時.
在某些實施方案中，異源多聚體蛋白質複合物以第一和第二氧還蛋白之間的融合多肽的形式產生，其中第一氧還蛋白是硫氧還蛋白而第二氧還蛋白是硫氧還蛋白還原酶。在一個實施方案中，第二重組多肽例如硫氧還蛋白還原酶相對於第一重組多肽如硫氧還蛋白位於N端。因此，分類為硫氧還蛋白的任何蛋白質，如NADPH硫氧還蛋白系統中的硫氧還蛋白成分和存在於鐵氧還蛋白/硫氧還蛋白系統中的硫氧還蛋白(也稱作TRx和TRm)可以與任何硫氧還蛋白還原酶如NADPH硫氧還蛋白還原酶和鐵氧還蛋白硫氧還蛋白還原酶以及能夠還原硫氧還蛋白的任何其它蛋白質組合使用。在特定實施方案中，此硫氧還蛋白和硫氧還蛋白還原酶來源於植物。
在一個備選實施方案中，使用可從麻風分枝桿菌獲得的編碼硫氧還蛋白/硫氧還蛋白還原酶蛋白質融合物的天然核酸序列(Wieles等(1995)J.Boil.Chem.2725604-25606)，見本文實施例所述。
免疫球蛋白在本發明另一實施方案中，多聚體蛋白質複合物是免疫球蛋白。本文中，「免疫球蛋白多肽鏈」是指能夠與第二多肽結合形成免疫學活性(例如能夠與抗原結合)多聚體蛋白質複合物的第一多肽。考慮用於此處的免疫球蛋白和免疫球蛋白多肽鏈的類型包括輕鏈和重鏈的免疫學活性(例如抗原結合)部分。用於此處的示例性免疫球蛋白和免疫球蛋白多肽鏈包括基本上完整的免疫球蛋白(包括任何IgG，IgA，IgD，IgE和IgM)以及免疫球蛋白的任何部分(包括稱作Fab片斷、Fab』片斷、F(ab』).sub2片斷和Fv片斷的那些部分)。
在此實施方案中，第一重組多肽可以是任何免疫球蛋白重鏈，包括任何IgG，IgA，IgD，IgE或IgM重鏈，而第二重組多肽可以是κ或λ免疫球蛋白輕鏈。因此，本文提供了製備免疫球蛋白的方法，所述方法包括(a)在包含油體的細胞中產生第一免疫球蛋白多肽鏈和第二免疫球蛋白多肽鏈，其中所述第一免疫球蛋白多肽鏈能夠和所述第二免疫球蛋白多肽鏈結合形成所述免疫球蛋白；和(b)通過能夠結合所述油體和所述第一免疫球蛋白多肽鏈的油體靶向蛋白使所述免疫球蛋白和油體結合。
本文中，多聚體免疫球蛋白通過油體靶向蛋白與油體結合。在特定實施方案中，油體靶向蛋白可以是包含油體蛋白和免疫球蛋白結合蛋白如A蛋白、L蛋白和G蛋白的融合多肽。
在再一涉及免疫球蛋白的實施方案中，第一和第二重組多肽(免疫球蛋白)獨立地與油體蛋白例如油質蛋白或caleosin融合。例如，a)第一重組多肽可以是免疫球蛋白重鏈，包括任何IgG，IgA，IgD，IgE或IgM重鏈，而第二重組多肽可以是κ或λ免疫球蛋白輕鏈；或b)第一重組多肽可以是來自免疫球蛋白重鏈的可變區和第一恆定區，而第二重組多肽可以是κ或λ免疫球蛋白輕鏈；或c)第一重組多肽可以是來自免疫球蛋白重鏈的可變區，而第二重組多肽可以是來自κ或λ免疫球蛋白輕鏈的可變區。
在某些實施方案中，可以對融合多肽進行設計或選擇以允許免疫球蛋白輕鏈和重鏈序列在包含油體的細胞中於油體上形成異源多聚體蛋白質複合物。包含油體靶向蛋白和第一和/或第二重組多肽、多聚體蛋白質複合物、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽或第一和/或第二硫氧還蛋白相關蛋白的表達載體的製備根據本發明，可以方便地在細胞中產生第一和/或第二重組多肽、多聚體蛋白質複合物、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽或第一和/或第二硫氧還蛋白相關蛋白；和油體靶向蛋白。為了產生重組多肽或多聚體蛋白質複合物，將編碼第一和/或第二重組多肽、多聚體蛋白質複合物、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽或第一和/或第二硫氧還蛋白相關蛋白；和/或油體靶向蛋白的核酸序列摻入重組表達載體中。因此，本文提供了包含本文所述嵌合核酸的重組表達載體，此表達載體適於表達油體靶向蛋白和第一和/或第二重組多肽、多聚體蛋白質複合物、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽或第一和/或第二硫氧還蛋白相關蛋白，並適於所選細胞。術語「適於在所選細胞中表達」是指重組表達載體含有確保在所選細胞中表達所必需的所有核酸序列。
因此，重組表達載體還含有基於用於表達的細胞選擇的調節核酸序列，其與編碼重組多肽或多聚體蛋白質複合物和/或油體靶向蛋白的核酸序列可操作地連接確保轉錄的起始和終止。調節核酸序列包括啟動子、增強子、沉默子、核糖體結合位點、Shine-Dalgarno、內含子和其它表達元件。「可操作連接」旨在指包含與編碼重組多肽或多聚體蛋白質複合物和/或油體靶向蛋白的核酸序列連接的調節區域的核酸序列允許在細胞內進行表達。典型的核酸構建體按5』至3』方向包含能夠指導表達的啟動子區域、包含第一和/或第二重組多肽、多聚體蛋白質複合物、異源多聚體蛋白質複合物、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽或第一和/或第二硫氧還蛋白相關蛋白；和/或油體靶向蛋白的編碼區和在所選細胞中起作用的終止區域。
調節序列的選擇取決於用於表達第一和/或第二重組多肽、多聚體蛋白質複合物、異源多聚體蛋白質複合物、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽或第一和/或第二硫氧還蛋白相關蛋白；和/或油體靶向蛋白的生物體和細胞類型，並且可能影響多肽的表達水平。調節序列是本領域已知的並可以選擇以指導油體靶向蛋白和重組多肽或多聚體蛋白質複合物在細胞中的表達。
可以用於細菌細胞的啟動子包括lac啟動子(Blackman等(1978)Cell1365-71)、trp啟動子(Masuda等(1996)Protein Eng 9101-106)和T7啟動子(Studier等(1986)J.Mol.Biol.189113-130)。可以用於本發明的在植物細胞中起作用的啟動子包括組成型啟動子如35SCaMV啟動子(Rothstein等(1987)Gene 53153-161)、肌動蛋白啟動子(McElroy等(1990)Plant Cell 2163-171)和泛素啟動子(歐洲專利申請0 342 926)。其它啟動子對某些組織或器官(例如，根、葉、花或種子)或細胞類型(例如，葉表皮細胞、葉肉細胞或根皮層細胞)特異或對植物發育的某些階段特異。表達的時機可以通過選擇誘導型啟動子予以控制，所述啟動子例如PR-a啟動子(見美國專利5,614,395)。因此，啟動子的選擇取決於積累期望多肽的期望位置和時機。在一個特定實施方案中，在種子細胞中表達第一和/或第二重組多肽、多聚體蛋白質複合物、異源多聚體蛋白質複合物、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽或第一和/或第二硫氧還蛋白相關蛋白；和油體靶向蛋白，並利用種子特異性啟動子。可以用於本發明中的種子特異性啟動子包括例如菜豆蛋白啟動子(Sengupta-Gopalan等(1985)Proc.Natl.Acad.Sci.USA823320-3324)和鼠耳芥屬18kDa油質蛋白啟動子(van Rooijen等(1992)Plant Mol.Biol.181177-1179)。可用於多種植物細胞類型中的新啟動子被不斷發現。眾多的植物啟動子實例可以參見Ohamuro等(Biochemof Pl.(1989)151-82)。
可以將能夠增強多肽表達的遺傳元件包括在表達載體中。在植物細胞中，這些元件包括例如來自病毒的非翻譯前導序列如AMV前導序列(Jobling和Gehrke(1987)Nature325622-625)和與玉米泛素啟動子聯合的內含子(見美國專利5,504,200)。
轉錄終止子一般是本領域已知的，處理充當轉錄終止信號外還充當延長mRNA半衰期的保護性元件(Guarneros等，(1982)Proc.Natl.Acad.Sci.USA79238-242)。在用於植物細胞內表達的核酸序列中，轉錄終止子典型地為大約200個核苷酸至約1000個核苷酸長。可以用於本發明中的終止序列包括例如，胭脂鹼合成酶終止區域(Bevan等(1983)Nucl.Acid.Res.11；369-385)、菜豆蛋白終止子(van der Geest等(1994)Plant J.6413-423)、根癌農桿菌(Agrobacterium tumefaciens)章魚鹼合成酶基因的終止子或其它具有類似功能的元件。轉錄終止子可以按An(1987)Methods in Enym.153292中描述的方法獲得。轉錄終止子的選擇可能影響轉錄的速率。
因此，本發明提供了嵌合核酸序列，其編碼第一和/或第二重組多肽、多聚體蛋白質複合物、異源多聚體蛋白質複合物、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽和/或硫氧還蛋白相關蛋白。在一個實施方案中，所述核酸包括(a)編碼油體靶向蛋白的第一核酸序列；(b)在閱讀框內與第一核酸序列可操作連接的、編碼第一重組多肽、免疫球蛋白多肽鏈或氧還蛋白的第二核酸序列；(c)在閱讀框內與第二核酸序列可操作連接的、編碼第二重組多肽、免疫球蛋白多肽鏈或氧還蛋白的第三核酸序列，其中所述第一和第二重組多肽、免疫球蛋白多肽鏈或氧還蛋白能夠形成多聚體蛋白質複合物。
在另一實施方案中，本發明提供了表達載體，其包含1)能在所述細胞中調節轉錄的第一核酸序列；2)與1)可操作地連接的、編碼重組融合多肽的第二核酸序列，其中所述第二核酸序列包含(i)編碼足以使所述重組融合多肽靶向油體的油體蛋白部分的核酸序列和與之在閱讀框中連接的(ii)編碼多聚體融合蛋白(例如氧還蛋白融合多肽或免疫球蛋白)的核酸序列，所述多聚體融合蛋白包含相互連接的第一重組多肽如氧還蛋白或免疫球蛋白多肽鏈和第二重組多肽如第二氧還蛋白或第二免疫球蛋白多肽鏈；3)與2)可操作連接的能夠在所述細胞中終止轉錄的第三核酸序列。
重組表達載體還可以含有標記基因。可以用於本發明的標記基因包括允許從未轉化的細胞中區別出轉化細胞的所有基因，包括所有可選擇和可篩選的標記基因。標記可以是允許通過化學手段篩選性狀的抗性標記如對抗例如卡那黴素、氨苄青黴素、G418、博來黴素、潮黴素、氯黴素的抗生素抗性標記，或耐受性標記，例如對抗化學藥物如正常的植物毒性糖甘露糖的耐受性標記(Negrotto等(2000)Plant Cell Rep.19；798-803)。在植物重組表達載體中，可以方便地使用除草劑抗性標記，例如賦予對草甘膦(US專利4,940,935和5,188,642)或膦絲菌素(White等(1990)Nucl.Acids Res.181062；Spencer等(1990)Theor.Appl.Genet.19625-631)的抗性的標記。當與氧還蛋白或油體靶向蛋白緊密鄰接時，除草劑抗性標記可以用於在植物細胞群體或植物上維持選擇壓力選擇出未喪失目的蛋白質的那些植物。可以通過視覺觀察用於鑑定轉化體的可篩選標記包括β-葡糖醛酸糖苷酶(GUS)(見美國專利US5,268,463和US5,599,670)和綠色螢光蛋白(GFP)(Niedz等(1995)Plant Cell Rep.14；403)。
重組表達載體還可以含有編碼確保靶向細胞區室或細胞器的引導信號的核酸序列。可以用於此的適宜引導信號包括能夠使多肽靶向內膜系統的那些。可以用於此的示例性引導信號包括能夠指導蛋白質前往周質、細胞質、高爾基器、質外體(Sijmons等1990，Bio/Technology，8217-221)、葉綠體(Comai等(1988)J.Biol.Chem.26315104-15109)、線粒體、過氧化物酶體(Unger等(1989)Plant Mol.Biol.13411-418)、ER、液泡(Shinshi等(1990)Plant Mol.Biol.14357-368)和油體的引導信號。包括適宜引導序列可以指導油體靶向蛋白或第一和/或第二重組多肽、多聚體蛋白質複合物、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽和/或硫氧還蛋白相關蛋白前往期望的細胞器或細胞區室。
本發明重組表達載體可以根據分子生物學領域技術人員熟知的方法學製備(見例如Sambrook等(1990)Molecular Cloning，第2版，ColdSpring Harbor Press)。這些構建體的製備可能涉及諸如限制性消化、連接、凝膠電泳、DNA測序和PCR等技術。可以獲得多種克隆載體以完成必需的克隆步驟，獲得保證多肽表達的重組表達載體。尤其適宜此目的的是具有能夠在大腸桿菌中發揮作用的複製系統的載體，如pBR322、pUC載體系列、M13mp載體系列、pBluescript等。典型地，這些載體含有允許例如通過賦予抗生素抗性篩選轉化細胞的標記。可以將核酸序列引入這些載體中，然後可以將載體引入大腸桿菌中，在適當培養基上培養該大腸桿菌。可以在收穫和裂解細胞後從細胞中回收到載體。
適宜將核酸序列引入植物細胞中的重組表達載體包括基於農桿菌(Agrobacterium)和根瘤菌(Rhizobium)的載體，如Ti和Ri質粒。基於農桿菌的載體典型地帶有至少一個T-DNA邊界序列，包括諸如pBIN19(Bevan(1984)Nucl.Acids Res.Vol.12，228711-8721)等載體和其它二元載體系統(例如US專利4,940,838)。包含第一和/或第二重組多肽、多聚體蛋白質複合物、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽和/或第一和/或第二硫氧還蛋白蛋白相關蛋白和油體靶向蛋白的細胞的製備根據本發明，向所選細胞中引入重組表達載體，然後培養所選細胞以直接地或在子代細胞中產生第一和/或第二重組多肽、多聚體蛋白質複合物、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽、第一和/或第二硫氧還蛋白蛋白相關蛋白；和油體靶向蛋白。
將重組表達載體引入細胞中的方法學本文中也稱作「轉化」，是本領域熟知的並隨著所選細胞類型的不同而不同。將重組表達載體轉移至細胞中的一般技術包括電穿孔；化學介導的技術，如CaCl2介導的核酸攝取；微粒轟擊(生物轟擊，biolistics)；利用天然感染性核酸核酸，如病毒來源的核酸序列或使用植物時來源於農桿菌或根瘤菌的核酸序列；PEG介導的核酸攝取、顯微注射、和利用碳化矽須晶(silicone carbidewhiskers)(Kaeppler等(1990)Plant Cell Rep.9415-418)，所有這些技術均可以用於本文中。
將重組表達載體引入細胞中可能導致其完全或部分攝取物整合入宿主細胞基因組(包括染色體DNA或質體基因組)中。或者，重組表達載體可能不整合至基因組中而是獨立於宿主細胞的基因組DNA進行複製。一般利用核酸序列的基因組整合，因為這使得可以通過隨後的細胞傳代實現引入的核酸序列的穩定遺傳和細胞、植物或動物系的構建。
特定實施方案涉及使用植物細胞。本文所用特定植物細胞包括可以從蘇木樹(Betholletia excelsa)；蓖麻(Riccinus communis)；椰子(Cocusnucifera)；芫荽(Coriandrum sativum)；棉花(Gossypium spp.)；落花生(Arachis hypogaea)；希蒙得木(Simmondsia chinensis)；亞麻子/亞麻(Linum usitatissimum)；玉米(Zea mays)；芥菜(芥屬(Brassicaspp.)和歐白芥(Sinapis alba))；油棕(Elaeis guineeis)；油橄欖(Oleaeuropaea)；菜籽油菜(Brassica spp.)；紅花(Carthamus tinctorius)；大豆(Glycine max)；南瓜(Cucurbita maxima)；大麥(Hordeum vulgare)；小麥(Traeticum aestivum)和向日葵(Helianthus annuus)獲得的細胞。
用於雙子葉植物物種的轉化方法學是熟知的。一般利用農桿菌介導的轉化，因為此方法具有高效率並對許多(即使不是所有的)雙子葉植物物種是易於實現的。農桿菌轉化一般涉及通過與帶有重組二元載體的大腸桿菌和帶有輔助質粒(能夠使二元載體進入靶農桿菌菌株)的大腸桿菌進行三親本交配，或通過DNA轉化農桿菌菌株(Hofgen等，Nul.Acids.Res.(1988)169877)，將包含目的DNA的二元載體(例如pBIN19)轉移至適宜的農桿菌菌株(如CIB542)中。可以用於轉化雙子葉植物物種的其它轉化方法學包括生物轟擊(Sanford(1988)Trends in Biotechn.6299-302)；電穿孔(Fromm等(1985)Proc.Natl.Acad.Sci.USA 825824-5828)；PEG介導的DNA攝取(Reich等，Bio/Techn.(1986)41001-1004)和碳化矽須晶(Kaeppler等(1990)Plant Cell Rep.9；415-418)。確切的轉化方法學典型地在某種程度上取決於所用的植物物種。
在一個特定實施方案中，從紅花中獲得油體，並在紅花中表達重組蛋白。紅花的轉化描述於Baker和Dyer(Plant Cell Rep.(1996)16106-110)。
單子葉植物物種現也可以使用多種方法學進行轉化，包括微粒轟擊(Christou等(1991)Biotechn.9957-962；Weeks等Plant Physiol.(1993)1021077-1084；Gordon-Kamm等Plant Cell(1990)2603-618)、PEG介導的DNA攝取(EP 0 292 435；0 392 225)或農桿菌介導的轉化(Goto-Fumiyuki等(1999)Nature-Biotech.17(3)282-286)。
質體轉化描述於US專利5,451,513；5,545,817和5,545,818；和PCT專利申請95/16783；98/11235和00/39313。基本的葉綠體轉化涉及使用例如生物轟擊或原生質體轉化將克隆的側翼為質體DNA的選擇標記和目的核酸序列一起引入適宜的靶組織中。可以使用的選擇標記包括例如細菌aadA基因(Svab等(1993)Proc.Natl.Acad.Sci.USA 90913-917)。可以使用的質體啟動子包括例如菸草clpP基因啟動子(PCT專利申請97/06250)。
在另一實施方案中，本文提供的本發明嵌合核酸構建體被直接地轉化至質體基因組中。質體轉化技術詳盡地描述於US專利5,451,513、5,545,817、5,545,818和5,576,198；PCT申請WO 95/16783和WO97/32977；McBride等，Proc Natl Acad Sci USA 917301-7305(1994)，所有這些的完整公開均特此併入作為參考。在一個實施方案中，質體轉化通過生物轟擊來進行，首先在單細胞綠藻Chlamydomonas reinhardtii中進行(Boynton等(1988)Science 2401534-1537)然後擴展到菸草(Nicotiana tabacum)(Svab等(1990)Proc Natl Acad Sci USA 878526-8530)並聯合對順式作用抗生素抗性位點(壯觀黴素或鏈黴素抗性)或對非光合突變表型互補的篩選。
在另一實施方案中，菸草質體轉化通過微粒轟擊葉或愈傷組織、或聚乙二醇(PEG)介導原生質體攝取質體DNA、利用側翼為克隆的質體DNA的抗生素抗性選擇標記來進行。例如，稱作引導序列的1至1.5kb側翼序列可以利於與質體基因組的同源重組，使得可以置換或修飾156kb菸草質體基因組中的特定區域。在一個實施方案中，可以利用質體16S rDNA和賦予壯觀黴素和/或鏈黴素抗性的rps 12基因中的點突變作為轉化的選擇標記(Svab等(1990)Proc Natl Acad Sci USA 878526-8530；Staub等(1992)Plant Cell 439-45，這些文獻的完整公開特此併入作為參考)，從而以大約每100次靶葉轟擊有1次的頻率得到穩定的同質轉化體。這些標記之間克隆位點的存在使得可以產生用於引入外源基因的質體靶向載體(Staub等(1993)EMBO J 12601-606，其整個公開特此併入作為參考)。在另一實施方案中，可以通過用顯性選擇標記，即編碼使壯觀黴素脫毒性的酶氨基糖苷-3』-腺苷醯轉移酶的細菌aadA基因(Svab等(1993)Proc Natl Acad Sci USA 90913-917，其整個公開特此併入作為參考)置換隱性rRNA或r-蛋白質抗生素抗性基因，實質性增加轉化頻率。該標記也已經被成功地用於高頻率轉化綠藻Chlamydomonas reinhardtii的質體基因組(Goldschmidt-Clermont，M.(1991)Nucl Acids Res 19，4083-4089，其整個公開特此併入作為參考)。在其它實施方案中，菸草和苔蘚Physcomitrella的原生質體的質體轉化可以使用PEG介導的DNA攝取(O』Neill等(1993)Plant J 3729-738；Koop等(1996)Planta 199193-201，其整個公開特此併入作為參考)進行。
微粒轟擊和原生質體轉化也可以考慮用於此。油籽植物的質體轉化已經成功地在鼠耳芥屬和芸苔屬植物中實現(Sikdar等(1998)Plant CellRep 1820-24；PCT申請00/39313，其完整公開特此併入作為參考)。
將嵌合核酸序列構建體插入包括能夠在植物質體中表達該構建體的啟動子的質體表達盒中。能夠在植物質體中表達的具體啟動子有例如，從質體基因編碼區上遊5』側翼區分離的啟動子，所述基因可以來自相同或不同物種，而且其天然產物典型地存在於大多數類型的質體中，包括非綠色組織中存在的那些質體。質體中的基因表達有別於核基因表達，與原核生物中的基因表達相關(Stern等(1997)Trends in Plant Sci.2308-315，其完整公開特此併入作為參考)。
質體啟動子一般含有原核生物啟動子所特有的-35和-10元件，而且稱作PEP(質體編碼RNA聚合酶)啟動子的一些質體啟動子被大多在質體基因組中編碼的大腸桿菌樣RNA聚合物所識別，而稱作NEP啟動子的其它質體啟動子被細胞核編碼的RNA啟動子識別。兩種類型的質體啟動子均適用於本發明。質體啟動子的實例包括clpP基因啟動子如菸草clpP基因啟動子(WO 97/06250，其完整公開特此併入作為參考)和鼠耳芥屬clpP基因啟動子(U.S.申請09/038,878，其完整公開特此併入作為參考)。能夠驅動嵌合核酸構建體在植物質體中表達的另一種啟動子來自質體16S核糖體RNA操縱子的調節區域(Harris等(1994)Microbiol Rev58700-754；Shinozaki等(1986)EMBO J 52043-2049，此兩份文獻的完整公開特此併入作為參考)。能夠驅動核酸構建體在植物質體中表達的啟動子的其它實例包括psbA啟動子或am rbcL啟動子。質體表達盒優選還包括與本發明嵌合核酸構建體可操作地連接的質體基因3』非翻譯序列(3』UTR)。非翻譯序列的作用在於優選指導轉錄RNA的3』加工而不是終止轉錄。3』UTR的例子是質體rps16基因3』非翻譯序列，或鼠耳芥屬質體psbA基因3』非翻譯序列。在再一實施方案中，質體表達盒包括poly-G序列代替3』非翻譯序列。質體表達盒還優選包括在植物質體中有作用的5』非翻譯序列(5』UTR)，其與本文提供的嵌合核酸構建體可操作地連接。
將質體表達盒包含在質體轉化載體中，該載體優選還包括用於通過同源重組向質體基因組中整合的側翼區。質體轉化載體可以任選地包括至少一個質體複製起點。本發明還包括使用該質體轉化載體轉化的植物質體，其中嵌合核酸構建體可在植物質體中表達。本發明還包括包含該植物質體的植物或植物細胞，包括其子代。在一個特定的實施方案中，所述植物或植物細胞，包括其子代對於轉基因質體而言是同質的。
能夠驅動嵌合核酸構建體在植物質體中表達的其它啟動子包括反式激活蛋白調節的啟動子，優選與植物或實施表達的植物細胞的亞細胞器或組分異源。在這些情況下，編碼反式激活蛋白的DNA分子可以插入適當的核酸表達盒中，然後可以將此表達盒轉化至植物細胞核DNA中。使用質體轉運肽可以使反式激活蛋白靶向質體。可以通過所選質體轉化系和包含DNA分子(其與核酸啟動子可操作連接，編碼添加有質體靶向序列的反式激活蛋白)的轉基因系雜交，或通過直接將含有期望DNA分子的質體轉化載體轉化至含有嵌合核酸構建體(其與細胞核啟動子可操作連接，編碼添加了質體靶向序列的反式激活蛋白)的轉基因系中，將反式激活蛋白和反式激活蛋白驅動的DNA分子結合起來。如果細胞核啟動子是誘導型啟動子，尤其是化學誘導型啟動子，則嵌合核酸構建體在植物質體中的表達可以通過向葉施用化學誘導劑激活。優選該誘導型反式激活蛋白介導的質體表達系統可以接受嚴格調節，在誘導之前不存在能檢測到的表達而在誘導後有非常高的表達和蛋白質積累。
一個具體的反式激活蛋白的例子是病毒RNA聚合酶。該類具體啟動子是可以被單亞基RNA聚合酶識別的啟動子，如能被噬菌體T7 DNA依賴性RNA聚合酶識別的T7基因10啟動子。優選將編碼T7聚合酶的基因轉化至細胞核基因組中，使用質體轉運肽使T7聚合酶靶向質體。適於基因(如編碼病毒RNA聚合酶如T7聚合酶的基因)的細胞核表達的啟動子如上文以及本申請中其它地方所述。嵌合核酸構建體在質體中的表達可以是組成型的或可以是誘導型的，該質體表達也可以是組織或器官特異性。各種表達系統的實例詳盡地描述在WO 98/11235中，其完整公開特此併入作為參考。因此，一方面，本發明利用靶向葉綠體的T7噬菌體RNA聚合酶(其處於化學誘導型PR-1a啟動子，如菸草PR-1啟動子的控制下)與和其可操作連接的接受T7基因10啟動子/終止序列調節的葉綠體報導轉基因(見例如US專利5,614,395所述，其完整公開特此併入作為參考)在細胞核基因組中的偶聯表達。另一實施方案中，當利用細胞核中表達T7啟動子的株系向與母體遺傳的TR或NTR基因同質的質體轉化體授粉時，得到帶有此兩個轉基因構建體的F1植物，其中，只有向葉施用PR-1a誘導劑苯並(1，2，3)噻二唑-7-硫代羥酸S-甲基酯(BTH)引發質體中大量酶學活性蛋白質合成後，此F1植物才可表達此兩個轉基因構建體。
在一個特定實施方案中，在操縱子樣多順反子基因中從單個啟動子出發由質體基因組轉錄出兩個或多個基因，如TR和NTR基因。在一個實施方案中，操縱子樣多順反子基因在其所包含的兩個基因之間包括一段間隔DNA序列。在一個特定實施方案中，此間隔DNA序列在質體基因組中並不存在，由此可以避免與質體序列的同源重組。在另一實施方案中，此DNA序列來源於非真核基因的5』非翻譯(UTR)區域，優選來自病毒5』UTR，優選來自噬菌體如T7、T3或SP6噬菌體的5』UTR。在一個實施方案中，可以對此DNA序列的部分進行修飾以防止在操縱子樣多順反子基因的RNA轉錄本中，如在此DNA序列和下遊基因的RBS之間形成RNA二級結構。該二級結構可以抑制或阻遏下遊基因的表達，尤其是翻譯的起始。該RNA二級結構可以通過運用計算機模型和程序如「mfold」程序版本3(可從Zuker和Turner，Washington University School of Medicine，St-Louis，MO獲得)和本領域技術人員已知的其它方法確定其溶化溫度來預測。
間隔DNA序列在操縱子樣多順反子基因中的存在增加了下遊基因的RBS的可接近性，由此導致更高的表達率。此策略適用於有待在操縱子樣嵌合異源多聚體基因中從單個啟動子出發由質體基因組表達的任何兩個或多個基因。
轉化後，一般在允許鑑定轉化體的選擇性培養基上培養細胞。可以根據本領域已知方法收穫細胞。為了使油體和第一和/或第二重組多肽、多聚體蛋白質複合物、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽和第一和/或第二硫氧還蛋白蛋白相關蛋白結合，可以使用任何能夠破壞細胞完整性的物理、化學或生物方法來破壞細胞的完整性。這些方法一般取決於細胞類型，並是本領域技術人員已知的。在使用植物的情況下，可以利用本領域技術人員一般已知的植物組織培養技術，從它們再生出成熟植物。可以收穫成熟轉化植物的種子用於繁殖此植物株系。也可以進行植物雜交，如此本發明還考慮各種遺傳背景的細胞系和轉基因植物的培育。也可以使包含第一重組多肽的植物系與包含第二重組多肽的植物系雜交。由此，本文還提供在植物中製備重組多聚體蛋白質複合物的方法，所述方法包括(a)製備包含如下細胞的第一植物，所述細胞包含油體和第一重組多肽，如氧還蛋白(例如硫氧還蛋白相關蛋白等)或免疫球蛋白多肽鏈，其中所述第一重組多肽能夠與所述油體通過油體靶向蛋白結合；(b)製備包含如下細胞的第二植物，所述細胞包含油體和第二重組多肽，如第二氧還蛋白(例如硫氧還蛋白相關蛋白等)或第二免疫球蛋白多肽鏈；和(c)使所述第一植物和所述第二植物進行有性雜交製備包含如下細胞的子代植物，所述細胞包含油體，其中所述油體能夠與所述第一重組多肽結合，而所述第一重組多肽能夠與所述第二重組多肽結合形成所述重組多聚體蛋白質複合物。
第二重組多肽也可以與油體結合。因此，本發明還提供了在植物中製備重組多聚體蛋白質複合物的方法，所述方法包括(a)製備包含如下細胞的第一植物，所述細胞包含油體和第一重組多肽，如氧還蛋白(或硫氧還蛋白相關蛋白)或免疫球蛋白多肽鏈，其中所述第一重組多肽能夠與所述油體通過油體靶向蛋白結合；(b)製備包含如下細胞的第二植物，所述細胞包含油體和第二重組多肽，如第二氧還蛋白(硫氧還蛋白相關蛋白)或第二免疫球蛋白多肽鏈，其中所述第二重組多肽能夠與所述油體通過油體靶向蛋白結合；和(c)使所述第一植物和所述第二植物進行有性雜交製備包含如下細胞的子代植物，所述細胞包含油體，其中所述油體能夠與所述第一重組多肽結合，而所述第一重組多肽能夠與所述第二重組多肽結合形成所述重組多聚體蛋白質複合物。
油體的分離本文提供的油體可以從任何含有油體的細胞，包括任何動物細胞、植物細胞、真菌細胞(如酵母細胞)、藻類細胞或細菌細胞中獲得。適於從細胞中分離出油體的任何方法都可以用於本發明中。從植物種子細胞中分離油體的方法描述在US專利(6,146,645和6,183,762)中，從酵母細胞中分離油體的方法描述在Ting等(1997)J.Biol.Chem.2723699-3706中。
在某些實施方案中，從植物細胞如花粉細胞；果實細胞；孢子細胞；堅果細胞；中果皮細胞如可從橄欖(Olea europaea)或鱷梨(Perseaamericana)獲得的中果皮細胞；或種子細胞中獲得油體。在特定實施方案中，從植物種子細胞中獲得油體。種子可以從本發明轉基因植物獲得。在特定實施方案中，本發明轉基因植物的種子含有第一和/或第二重組多肽、多聚體蛋白質複合物、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽或第一和/或第二硫氧還蛋白蛋白相關蛋白，濃度為總細胞種子蛋白質的至少約0.5％。在其它實施方案中，本發明提供的轉基因植物的種子含有重組多肽或多聚體蛋白質複合物，濃度為總細胞種子蛋白的至少約0.5％、0.6％、0.7％、0.8％、0.9％、1.0％、1.25％、1.5％、1.75％、2.0％、2.25％、2.5％、3％、4％、5％、6％、7％、8％、9％、10％或更多。重組多肽或多聚體蛋白質複合物濃度的上限可以高達約8％、9％、10％、11％、12％、13％、14％、15％。因此，至少約0.5％至多達約15％；至少約0.1％至多達約10％；及至少約5％至多達約8％的範圍均屬於本文所考慮的各種範圍。
在此方面有用的植物種子有可從選自如下的植物物種中獲得的植物種子蘇木樹(Betholletia excelsa)；蓖麻(Riccinus communis)；椰子(Cocus nucifera)；芫荽(Coriandrum sativum)；棉花(Gossypiumspp.)；落花生(Arachis hypogaea)；希蒙得木(Simmondsia chinensis)；亞麻子/亞麻(Linum usitatissimum)；玉米(Zea mays)；芥菜(芥屬(Brassica spp.)和歐白芥(Sinapis alba))；油棕(Elaeis guineeis)；油橄欖(Olea europaea)；菜籽油菜(Brassica spp.)；紅花(Carthamustinctorius)；大豆(Glycine max)；南瓜(Cucurbita maxima)；向日葵(Helianthus annuus)；大麥(Hordeum vulgare)；小麥(Traeticumaestivum)；和其混合物。在一個特定實施方案中，油體可以從紅花(Carthamus tinctorius)種子中獲得。
為了從植物種子中製備油體，按照普通農業操作培養植物並使其結籽。因此，本發明還提供包含油體的種子，其中所述油體還包含本文所述的本發明多聚體蛋白質複合物。一旦收穫種子並在需要時通過例如過篩或洗滌除去大量不溶性物質如石頭或種皮後，任何適宜從種子中分離出油體的方法都可以用於此處。典型的方法涉及研磨種子隨後進行水性提取步驟。
種子研磨可以使用任何粉碎方法進行，從而基本上破碎種子的細胞膜和細胞壁而又不損傷種子細胞中油體的結構完整性。在此方面，適宜的研磨方法包括機械擠壓和碾磨種子。溼磨法如描述用於棉花(Lawhon等(1977)J.Am.Oil Chem.Soc.63533-534)和大豆(US專利3,971,856；Carter等(1974)J.Am.Oil Chem.Soc.51137-141)的方法在此方面是特別有用的。能夠工業規模碾磨種子的適宜碾磨設備包括膠體磨、盤磨、針磨(pin mill)、軌道式磨、IKA磨和工業規模的勻化器。碾磨設備的選擇取決於所選種子以及生產量要求。
固體雜質如種皮、纖維性物質、不溶解的糖、蛋白質和其它不溶性雜質優選隨後使用基於大小排阻的方法學如過濾或基於重力的方法如基於離心的分離方法從磨碎的種子級分中除去。離心可以使用如沉降式離心機如HASCO 200 2-相沉降離心機或NX310B(Alpha Laval)實現。對操作條件進行選擇，以便實質性部分的不溶性雜質和沉澱可以從可溶性級分中分離出來。
在除去不溶性物質後，可以從水性級分中分離出油體級分。可以使用基於重量的方法以及基於大小排阻的技術。可以使用的基於重量的方法包括利用例如管式離心機如Sharples AS-16或AS-46(Alpha Laval)、盤式堆積離心機(disc stack centrifuge)或旋液分離器離心，或在自然重力下的相分離。可以使用的大小排阻方法包括膜超過濾和交叉流微過濾。
從水相分離固體和分離油體相也可以使用基於重力的分離方法或基於大小排阻的方法同時進行。
在此方法的該階段獲得的油體製品一般相對粗，且取決於油體的應用，可能期望除去其它雜質。能夠除去其它種子雜質的任何方法均可以用於此方面。方便地，從油體製品中除去這些雜質可以通過將油體製品重懸在水相中然後再離心重懸級分完成，該方法在本文中稱作「洗滌油體」。所選洗滌條件可以根據期望的油體級分純度而改變。例如，當將油體用於藥物組合物中時，一般可能期望純度高於用於食物製品中時所期望的純度。可以根據期望純度洗滌油體一次或多次，而且離子強度、pH和溫度均可以改變。可以使用分析技術監測雜質的去除。例如，可以使用SDS凝膠電泳監測種子蛋白的除去。
整個油體分離方法可以以分批方式或連續流方式進行。在一個特定實施方案中，利用工業規模的連續流方法。
通過這些和類似技術的應用，本領域技術人員能夠從任何含有油體的細胞中獲得油體。本領域技術人員將意識到，一般該方法在某種程度上取決於所用細胞類型。然而，可以進行此改變而不偏離本發明的範圍和精神。第一和/或第二重組多肽、多聚體蛋白質複合物、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽、第一和/或第二硫氧還蛋白蛋白相關蛋白與油體的結合根據本發明，油體與第一和/或第二重組多肽、多聚體蛋白質複合物、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽、第一和/或第二硫氧還蛋白蛋白相關蛋白的結合是通過能夠與這些多聚體蛋白質複合物及油體結合的油體靶向蛋白實現的。本文中，短語「油體與多聚體蛋白質複合物結合」是指使油體與多聚體蛋白質複合物接近以允許實現油體與第一和/或第二重組多肽、多聚體蛋白質複合物、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽或第一和/或第二硫氧還蛋白蛋白相關蛋白結合。油體與多聚體蛋白質複合物結合可以通過油體靶向蛋白與油體以及與多聚體蛋白質複合物的結合來完成。在特定實施方案中，表達多聚體蛋白質複合物的細胞與能從相同細胞中獲得的油體結合，這就使得可以方便地在包含油體的宿主細胞系統中產生和分離此多聚體蛋白質複合物，包括第一和/或第二重組多肽、多聚體蛋白質複合物、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽或第一和/或第二硫氧還蛋白蛋白相關蛋白。因此，在一個實施方案中，油體與多聚體蛋白質複合物在細胞的生長過程中在細胞內結合。例如，氧還蛋白融合多肽可以與油體蛋白融合，而該嵌合蛋白質可以在含有油體的植物種子中表達。在此情況下，從種子中分離油體將導致分離出包含第一和/或第二重組多肽、多聚體蛋白質複合物、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽或第一和/或第二硫氧還蛋白蛋白相關蛋白的油體。在多聚體蛋白質複合物與可從產生此複合物的相同細胞中獲得的油體結合的另一實施方案，在破碎細胞完整性後實現油體與多聚體蛋白質複合物的結合。
例如，可以以一定方式表達第一和/或第二重組多肽、多聚體蛋白質複合物、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽或第一和/或第二硫氧還蛋白蛋白相關蛋白，以便使其靶向種子細胞的內膜系統。這樣，在含有能夠與這些多聚體蛋白質複合物結合的油體靶向蛋白(例如與能夠和重組多肽或多聚體蛋白質複合物結合的單鏈抗體連接的油質蛋白)的相同種子細胞中存在的油體可以在研磨種子時與重組多肽或多聚體蛋白質複合物結合。
根據此實施方案，可以製備包含靶向植物質外體的免疫球蛋白的輕鏈和重鏈的植物種子細胞。製備這些特定種子細胞以進一步包含與能夠和免疫球蛋白結合的油體靶向蛋白(如油質蛋白-A蛋白融合蛋白等)結合的油體。在研磨種子時，包含A蛋白的油體通過結合方式與免疫球蛋白連接。
在再一實施方案中，用於和多聚體蛋白質複合物結合的油體是從不同於包含第一和/或第二重組多肽、多聚體蛋白質複合物、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽或第一和/或第二硫氧還蛋白蛋白相關蛋白的細胞的細胞來源獲得的，例如來自不同的植物系。例如，與A蛋白結合的油體可以從一個植物系製備。然後可以將這些油體與包含質外體表達的構成免疫球蛋白的輕鏈和重鏈的磨碎種子混合。或者，可以使包含與A蛋白結合的油體的植物系與包含免疫球蛋白的植物系雜交。
第一重組多肽、第二重組多肽和油體靶向蛋白也可以在不同的細胞區室中製備。然後第一多肽、第二多肽和油體可以在細胞整體性破壞後結合。例如，已知植物中存在各種機制可以用於引導基因產物，而且控制這些機制的運行的序列已得以某種詳細的表徵。例如，可以通過各種蛋白質氨基末端存在的轉運序列控制基因產物向葉綠體靶向，在向葉綠體運輸的過程中此轉運肽將被切除從而產生成熟蛋白質(Comai等(1988)JBiol Chem 26315104-15109)。其它基因產物定位於其它細胞器，如線粒體和過氧化物酶體(Unger等(1989)Plant Mol Biol 13411-418)。可以對編碼這些產物的cDNA進行操作以使異源基因產物導向這些細胞器。此外，造成基因產物導向其它細胞區室的序列也已得以表徵。
糊粉細胞中氨基端序列負責導向ER、質外體和細胞外分泌(KoehlerHo(1990)Plant Cell 2769-783)。此外，氨基端序列與羧基端序列結合負責基因產物導向液泡(Shinshi等(1990)Plant Mol Biol14357-368)。通過上述適當導向序列與目的轉基因序列的融合，可以指導轉基因產物靶向期望的細胞器或細胞區室。
如前述，使用本文提供的方法獲得的氧還蛋白與油體結合時具有酶學活性。優選，氧還蛋白以和另一氧還蛋白的氧還蛋白融合多肽形式產生比其以非融合多肽形式結合油體產生時(即，沒有第二氧還蛋白時)，活性高出至少5倍。更優選，當以氧還蛋白融合多肽形成產生時，氧還蛋白的活性高出至少10倍。
可以根據本領域一般已知的方法確定氧還蛋白融合多肽的活性(見例如Johnson等(1984)J.of Bact.Vol 158 31061-1069)，並可以通過例如添加去汙劑(包括離子型和非離子型去汙劑)優化。
油體的配製根據一個特定實施方案，優選將包含第一和/或第二重組多肽、多聚體蛋白質複合物、異源多聚體蛋白質複合物、多聚體融合蛋白、異源多聚體融合蛋白、免疫球蛋白、免疫球蛋白多肽鏈、氧還蛋白融合多肽或第一和/或第二硫氧還蛋白相關蛋白的油體配製成乳劑。所述乳劑優選用於製備藥物組合物、個人護理品或食品。以乳化的形式，油體賦予了某些期望性質，例如與人皮膚的良好相容性。
在特定實施方案中，對油體製劑進行穩定化以便可以獲得可以保存和貯藏更長時期的終產物。本文中，術語「穩定化的油體製品」是指這樣的油體製品，在該油體製品保存時製劑由於經過一定方式的配製以致不會經歷不期望的物理或化學改變。穩定化的要求可以根據終產物而改變。例如，個人護理產品優選在室溫下保持至少一年的穩定，並同時能夠耐受短期的溫度波動。藥物製劑由於可以在較低溫度下貯存由此防止不期望的反應發生，故它們可以在一些情況下是不太穩定的。
一般地，可以用於此的穩定化技術包括可以用於保存生物材料的任何和全部方法，包括添加化學藥物、基於溫度調節的方法、基於輻射的方法和其組合。在特定實施方案中，將少量穩定化化學藥物與油體製劑混合以達到穩定化。這些化學藥物包括尤其是防腐劑、抗氧化劑、酸、鹽、鹼、粘度調節劑、乳化劑、成膠劑和其混合物，並且它們均可以用於穩定油體製品。鑑於氧還蛋白融合多肽的存在，穩定化試劑一般經選擇與此氧還蛋白融合多肽相容並導致該氧還蛋白融合多肽具有良好的酶促功能。
評價油體製品的穩定性的診斷參數可以按需要確定，包括可指示化學或物理穩定性方面的不期望的定性或定量改變的所有參數。隨時間推移評價油體製品的典型參數包括顏色、氣味、粘性、質地、pH和微生物生長及酶活性。
在特定實施方案中，在加入可以用於製備終產物的其它成分之前對油體製劑進行穩定化處理。然而，在其它實施方案中，可以使用未經穩定化的油體配製最終製劑然後對最終製劑進行穩定化處理。
可以使用適宜製備包含油體的製劑的一個或多個其它成分和任何配製方法來獲得此最終製品。所用成分和方法一般將取決於最終產物的期望用途，並且是本領域已知的且可以按需要確定。可以用於此的成分和方法包括描述在US專利(US專利6,146,645和6,183,762，併入此處作為參考)中的那些。
在特定實施方案中，氧還蛋白融合多肽包含硫氧還蛋白和硫氧還蛋白還原酶。因此，本文提供了包含硫氧還蛋白/硫氧還蛋白還原酶融合多肽的油體。本文還提供含有如下油體的製劑，所述油體包含能夠治療或保護靶標使其抗氧化壓力的硫氧還蛋白/硫氧還蛋白還原酶。可以通過使靶標與製劑接觸，治療或預防靶標使其抗壓力。所述靶標可以是易受氧化壓力影響的任何物質，包括任何分子、分子複合物、細胞、組織或器官。
在另一實施方案中，本文提供含有油體的製劑，所述油體包含能夠化學還原靶標的硫氧還蛋白/硫氧還蛋白還原酶。可以通過使靶標與製劑接觸來還原靶標。所述靶標可以是易於受到還原作用影響的任何物質，包括任何分子或分子複合物。在此方面尤其敏感的靶標是蛋白質中存在的二硫鍵。
包含硫氧還蛋白/硫氧還蛋白還原酶的油體可以用於製備製劑來降低食物的變應原性或增加食物的可消化性。優選地，降低食物變應原性的方法通過混合包含硫氧還蛋白/硫氧還蛋白還原酶的油體和食物或食物成分來實施，其中所述食物或食物成分可以選自各種來源，包括例如小麥麵粉、小麥麵團、奶、乾酪、大豆、酸牛奶和冰淇淋。包含硫氧還蛋白/硫氧還蛋白還原酶的油體還可以用於增加奶以及含有二硫鍵的其它蛋白質的可消化性(Jiao，J.等(1992)J.Agric.Food Chem402333-2336)。其它的食物應用包括利用包含硫氧還蛋白/硫氧還蛋白還原酶的油體作為食物添加劑以增加麵團強度和麵包的質量性質(Wong等(1993)J.Cereal Chem.70113-114；Kobrehel等(1984)GlutenProteinsAssociation of Cereal Research；Detmold，德國)。
本文還提供藥物組合物，其在藥物活性載體中包含含有硫氧還蛋白/硫氧還蛋白還原酶的油體；含有多聚體蛋白質複合物，如異源多聚體蛋白質複合物的油體；分離的硫氧還蛋白/硫氧還蛋白還原酶融合蛋白；或分離的多聚體蛋白質複合物。這些藥物組合物可以用於治療再灌注損傷(Aota等(1996)J.Cardiov.Pharmacol.(1996)27727-732)、白內障(US專利US 4,771,036)、慢性阻塞性肺病(COPD)(MacNee等(1999)Am.J.Respir.Crit.Care Med.160S58-S65)、糖尿病(Hotta等，J.Exp.med.188；1445-1451)、螫刺毒作用(PCT專利申請99/20122；US專利5,792,506)、支氣管肺病(MacNee(2000)Chest 1173035-3175)、惡性腫瘤(PCT專利申請91/04320)，以及緩解潛在的空氣傳播性(如花粉起源的)和接觸性變應原引起的過敏(PCT專利申請00/44781)。可以使用本文所述藥物組合物治療的其它疾病或病症包括銀屑病、傷口癒合、膿毒病、GI出血、腸道疾病(IBD)、潰瘍、移植、GERD(胃食管反流病)。
在另一實施方案中，本文提供的藥物組合物，尤其是包含單純的一種或多種氧還蛋白或還包含油體的那些藥物組合物可以通過還原性失活磷脂酶A2(炎性疾病中的一種起作用的因素)用於治療炎性或病毒性疾病。此外，已經發現氧還蛋白融合多肽系統可以充當一種自身防衛機制響應環境刺激，包括由UV產生的自由基造成的氧化壓力。因此，氧還蛋白(如本文所述油質蛋白-硫氧還蛋白，油質蛋白-硫氧還蛋白還原酶，各種氧還蛋白融合多肽)可以在某些皮膚疾病中產生有益效果，所述皮膚疾病如銀屑病、皮膚癌、皮屑(dandruff)、尿布疹、皮炎、痤瘡、曬傷、老化、炎症等。
在另一實施方案中，還可以使用油體-硫氧還蛋白相關融合蛋白如油質蛋白-硫氧還蛋白還原酶作為毒液的解毒劑。許多動物毒液和其它毒素含有二硫鍵，包括所有的蛇毒神經毒素、一些細菌神經毒素(包括破傷風毒素和肉毒桿菌A)、蜜蜂毒磷脂酶A2和蠍毒。在再一實施方案中，本文提供的氧還蛋白相關藥物組合物可以通過還原二硫鍵失活毒液毒素。治療被毒液或毒素作用的個體的方法可以包括步驟施用有效劑量的藥物組合物，所述組合物於藥物有效載體中，其量足以緩解或逆轉毒液毒素對個體的影響。
本文提供的藥物組合物優選配製成單劑量給藥形式。對於遞送施用後在預期治療中將有效的量而言，製劑中化合物的濃度是有效的。典型地，將組合物配製成單劑量給藥形式。為了配製組合物，將該重量分數的化合物或其混合物溶解、懸浮、分散或以其它方式混合在選定的賦形藥中達到有效濃度，以致可以緩解或改善所治療的病症。適於施用本文提供的化合物的藥物載體或賦形藥包括本領域技術人員已知的適於具體給藥模式的任何此類載體。
此外，可以將化合物作為唯一的藥物活性成分配製在組合物中或可以使其和其它活性成分聯合。脂質體懸浮液，包括靶向組織的脂質體，也可以適用作藥物可接受載體。可以根據本領域技術人員已知方法製備這些。例如，可以按US專利4,522,811所述製備脂質體製劑。
將活性化合物包括在可藥用載體中，其量足以對所治療的患者造成治療上有用的效果而不會產生未期望的副作用。治療有效濃度可以通過在已知的體外和體內系統中，如本文提供的試驗中測試化合物經驗性地確定。
活性化合物在藥物組合物中的濃度取決於活性化合物的吸收、失活和排洩速率、化合物的物化特徵、給藥計劃和給藥量以及本領域技術人員已知的其它因素。
典型地，考慮治療上有效的劑量。給藥量可以為每ml血液體積大約0.001至1mg，優選大約0.005-0.05mg，更優選大約0.01mg。製備每劑量單位可以提供大約1mg至大約1000mg、優選大約10至大約500mg、更優選大約25-75mg基本活性成分或基本成分的組合的藥物單位劑型。可以經驗確定精確劑量。
活性成分可以一次給藥，或可以分成數個較小劑量間隔給藥。應當理解，精確劑量和治療持續時間是所治療疾病的函數，並且可以使用已知的測試方法經驗確定或由體內或體外測試數據外推確定。應當注意的是，濃度和劑量值也可以隨待緩解的病症的嚴重性改變。還應理解，對於任何特定對象，應根據個體需要以及施用或監控組合物給藥的人的職業判斷，隨時間調整具體的給藥方案，並且應理解，本文給出的濃度範圍僅在於舉例說明並在於限制所要求保護的組合物和含有其的組合的範圍或應用。
優選的可藥用衍生物包括酸、鹽、酯、水合物、溶劑合物和前藥形式。一般對衍生物進行選擇以便其藥物動力學性質優於相應的中性化合物。
因此，可以將有效濃度或量的本文提供的一種或多種化合物或其可藥用衍生物與用於全身、局部或區域性給藥的適宜藥物載體或賦形藥混合以形成藥物組合物。化合物以對改善或治療疾病(治療方案所考慮的疾病)的有效的量包括在內。活性化合物在組合物中的濃度取決於活性化合物的吸收、失活、排洩速率、給藥策略、給藥量、具體劑型以及本領域已知的其它因素。
用於胃腸外、皮內、皮下或局部應用的溶液或懸浮液可以包括如下任何成分無菌稀釋液如注射用水、鹽水溶液、固定油、聚乙二醇、甘油、丙二醇或其它合成溶劑；抗微生物劑，如苯甲醇和對羥基苯甲酸甲酯；抗氧化劑，如抗壞血酸和亞硫酸氫鈉；螯合劑如乙二胺四乙酸(EDTA)；緩衝液如乙酸鹽、檸檬酸鹽和磷酸鹽；和調節滲透壓的試劑如氯化鈉或葡萄糖。可以將胃腸外製劑密封在玻璃、塑料或其它適宜物質製成的安瓿、一次性注射器或單或多劑量小瓶中。
在化合物表現出不充分的溶解度的情況下，可以使用溶解化合物的方法。這些方法時本領域技術人員已知的，包括但不限於使用共溶劑如二甲基亞碸(DMSO)、使用表面活性劑如Tween_、或溶解在碳酸氫鈉水溶液中。化合物的衍生物，如化合物的前藥也可以用於配製有效藥物組合物。對於眼部適應症，可以將組合物配製在可眼用載體中。對於本文的眼用，優選通過局部給藥或通過注射區域給藥，緩釋製劑也可能是期望的。典型地，將組合物配製成單劑量給藥形式，以便一次給藥即可以給予有效量。
一旦載體中混合或加入了化合物，得到的混合物可以是溶液、混懸液、乳液或其它組合物。所獲混合物的形式取決於多種因素，包括預期的給藥模式和混合物在所選載體或賦形藥中的溶解度。如果必要，可以配製化合物的可藥用鹽或其它衍生物。
可以將化合物包括在可藥用載體中，其含量足以在所治療的患者身上造成治療有用的效果，同時不引起不期望的副作用。應當理解，副作用的數量和程度取決於施用化合物所針對的病症。例如，在治療危及生命的疾病時某些毒性和不期望的副作用是可容忍的，但在治療後果較不嚴重的疾病時則是不能容忍的。
化合物還可以和不損害期望的作用的其它活性物質混合，或與增補期望作用的本領域技術人員已知物質混合。本文所用的混合物和藥劑的製劑包括適於口服、直腸、局部、吸入、口腔(例如舌下)、胃腸外(例如皮下、肌內、皮內或靜脈)、透皮給藥或任何途徑的那些製劑。在所有給出的情況中，最適宜的途逕取決於所治療病症的性質和嚴重性並取決於所用具體活性化合物的性質。可以提供含有適宜數量的化合物或其可藥用衍生物的單位劑型製劑，如片劑、膠囊、藥丸、粉末、顆粒、無菌胃腸外給藥溶液或混懸液及口服溶液或混懸液、和油-水乳劑，施用給人和動物。一般地，以單位劑型或多劑量形式配製和施用藥物治療活性化合物和其衍生物。本文所用單位劑量形式是指如本領域已知適於人和動物對象並獨立包裝的物理離散單位。每個單位劑量含有主要量的治療活性化合物(此含量將足以產生期望的療效)和所需的可藥用載體、賦形藥或稀釋液。單位劑型的實例包括安瓿、裝片劑或膠囊的小瓶、品脫或加侖瓶。因此，多劑量形式是多個在包裝時未分開的單位劑量。
組合物可以含有活性成分和稀釋劑如乳糖、蔗糖、磷酸二鈣或羧甲基纖維素；潤滑劑如硬脂酸鎂、硬脂酸鈣和滑石；及粘合劑如澱粉、天然膠(如金合歡膠)、葡萄糖、糖蜜、聚乙烯吡咯烷酮、纖維素和其衍生物、聚維酮、交聯聚維酮和本領域技術人員已知的其它此類粘合劑。液體可藥用組合物可以例如通過在載體(如水、鹽水、水性葡萄糖、甘油、乙二醇、乙醇等)中將上述活性成分和任選地藥物輔料一起溶解、分散或其它方式混合，由此形成溶液或混懸液。如果期望的話，待施用的藥物組合物還可以含有小量的無毒性輔助物質，如潤溼劑、乳化劑或增溶劑、pH緩衝劑等，例如乙酸鹽、檸檬酸鈉、環糊精衍生物、失水山梨糖醇單月桂酸酯、三乙醇胺乙酸鈉、油酸合三乙醇胺、和其它此類試劑。製備此類劑型的方法是本領域技術人員已知的或是明顯的(見如Remington’sPharmaceutical Sciences，Mack Publishing Company，Easton，Pa.，第15版，1975)。待施用的組合物或製劑將含有數量足以緩解所治療對象的症狀的活性化合物。
可以製備含有0.005％至100％活性成分以及剩餘量為無毒性載體的劑型或組合物。對於口服給藥，藥物組合物可以採取如片劑或膠囊的形式，所述形式可以根據常規方法採用可藥用賦形劑如粘合劑(如，預糊化玉米澱粉、聚乙烯吡咯烷酮或羥丙基甲基纖維素)；填充劑(例如，乳糖、微晶纖維素或磷酸氫鈣)；潤滑劑(例如，硬脂酸鎂、滑石或矽石)；崩解劑(例如，馬鈴薯澱粉或羥乙酸澱粉鈉)；或潤溼劑(例如，月桂基硫酸鈉)製備。可以按本領域熟知方法給片劑加包衣。
藥物製劑還可以採取液體形式，例如溶液、糖漿或混懸液，或可以採取臨用前可以用水或其它適宜載體重構的藥物產品形式。該液體製品可以通過常規方法使用可藥用添加劑如懸浮劑(如，山梨糖醇糖漿、纖維素衍生物或可食用氫化脂肪)；乳化劑(如，卵磷脂或阿拉伯樹膠)；非水性載體(例如，杏仁油、油性酯或分級分離的植物油)；和防腐劑(例如，甲基或丙基對羥基苯甲酸酯或山梨酸)製備。
適於直腸給藥的製劑優選採取單位劑量栓劑的形式。這些可以通過混合活性化合物和一種或多種常規固體載體(如可可脂)然後使所獲混合物成形來製備。
適於皮膚或眼睛局部施用的製劑優選採取油膏、霜劑、洗劑、糊劑、凝膠、噴霧劑、氣霧劑和油的形式。可以使用的載體包括凡士林、羊毛脂、聚乙二醇、醇類和其中兩種或多種的組合。局部製劑還可以有利地含有0.05至15％重量的增稠劑，所述增稠劑可選自羥丙基甲基纖維素、甲基纖維素、聚乙烯吡咯烷酮、聚乙烯醇、聚(烷撐二醇)、聚/羥基烷基、(甲基)丙烯酸酯或聚(甲基)丙烯醯胺。局部製劑常常通過滴入的方式或以油膏的形式施用於結膜囊內。其還可以用於溼潤或潤滑眼睛、面竇(facial sinuses)和外耳道。還可以將其注射入眼睛前房和其它地方。還可以在親水三維聚合物基質中製備液態局部製劑，其可採取條(strip)、隱形眼鏡等形式從中釋放出活性化合物。
通過吸入給藥時，在此所用化合物可以以氣霧劑噴霧給藥形式從加壓的包裝或噴霧器中利用適宜的拋射劑(如二氯二氟甲烷、三氯氟甲烷、二氯四氟乙烷、二氧化碳或其它適宜氣體)來遞送。對於加壓氣霧劑，劑量單位可以通過提供可遞送經計量的量的閥來決定。用於吸入器或吹藥器中的(如明膠)膠囊和藥筒可以經配製含有化合物和適宜粉末基質(如乳糖或澱粉)的粉末混合物。
適宜口腔(舌下)給藥的製劑包括例如在增味基質(通常為蔗糖和阿拉伯樹膠或黃蓍膠)中含有活性化合物的糖錠；在惰性基質(如明膠和甘油或蔗糖和阿拉伯樹膠)中含有化合物的錠劑。
可以將化合物配製成腸胃外給藥的形式，通過注射如快速濃注或連續灌注給藥。注射製劑可以以單位計量形式，例如在安瓿或多計量容器中和添加的防腐劑一起存在。組合物可以是在油性或水性載體中的懸浮液、溶液或乳液，並可以含有配製用試劑如懸浮劑、穩定劑和/或分散劑。或者，活性成分可以為粉末形式，在臨用可以使用適宜載體如無菌無致熱原的水或其它溶劑進行重配。
適宜透皮給藥的製劑可以為適合與受體表皮保持長期緊密接觸的離散貼劑。此類貼劑適宜含有任選緩衝的水溶液形式的活性化合物，此溶液中活性化合物的濃度為例如0.1至0.2M。適宜透皮給藥的製劑還可以通過離子電滲療法遞送(見例如，Pharmaceutical Research 3(6)，318(1986))和典型地採取活性化合物的任選緩衝水性溶液的形式。
藥物組合物還可以通過控釋手段和/或遞送裝置給藥(見，例如，US專利3,536,809；3,598,123；3,630,200；3,845,770；3,847,770；3,916,899；4,008,719；4,687,610；4,769,027；5,059,595；5,073,543；5,120,548；5,354,566；5,591,767；5,639,476；5,674,533和5,733,566)。
可以通過持續灌注活性物質維持期望的血液水平，這可由血漿水平確定。應當注意的是，由於毒性或骨髓、肝或腎功能不全，主治醫師將知道如何和在何時終止、中斷或調整療法到較低劑量。相反地，如果臨床反應不足(排除毒性副作用)，主治醫師也將明了如何和何時調整治療至較高水平。
單獨或與其它藥劑聯合的本文提供的藥物組合物的功效和/或毒性也可以通過本領域已知的方法評價(一般見，O』Reilly，InvestigationalNew Drugs，155-13)。
可以使用防止化合物從體內快速清除的載體，如緩釋劑或包衣等，製備活性化合物或可藥用衍生物。
本發明還提供含有組合物和/或聯合以及給藥說明書的藥盒。該藥盒還可以包括用於注射複合物的針或注射器(優選為無菌形式包裝)和/或包裝的醇墊片。任選包括有關臨床醫師或患者如何使用活性劑的說明書。
最後，包含任何前述藥劑的本發明提供的藥物組合物可以以生產物品的形式包裝，其中含有包裝材料、於包裝材料中的此處提供的化合物或其適宜衍生物(對治療本文所述病症或疾病有效的)、及指示該化合物或其適宜衍生物可用於治療本文所述疾病或病症的標記。此標記可以任選地包括該治療所適應的病症。
本文還提供含有油體的個人護理製劑，所述油體中含有硫氧還蛋白/硫氧還蛋白還原酶融合多肽。包含硫氧還蛋白和硫氧還蛋白還原酶的個人護理產品公開在例如日本專利申請JP9012471A2，JP103743A2和JP1129785A2中。可以根據本發明製備的個人護理製劑包括能夠改善暴露於有害環境刺激的皮膚的物理外觀的製劑，所述刺激可導致氧化壓力，例如由UV產生的自由基引起的氧化壓力。包含硫氧還蛋白/硫氧還蛋白還原酶的油體也可以用於製備護髮產品，其描述見US專利4,935,231和4,973,475(完整地併入此處作為參考)。
本文包括如下實施例僅用於舉例說明而非旨在限制本發明的範圍。
實施例1分離硫氧還蛋白和NADPH硫氧還蛋白還原酶基因從鼠耳芥生物資源中心(ABRC，http/aims.cps.msu.edu)鼠耳芥保藏中心獲得鼠耳芥長角果(Arabidopsis silique)cDNA文庫CD4-12，用作模板以分離鼠耳芥的硫氧還蛋白h(Trxh)和硫氧還蛋白還原酶基因。為了分離Trxh基因，合成如下引物GVR8335』TA 3』(SEQ ID NO1)粗體顯示了與Rivera-Madrid等(1993)Plant Physiol 102327-328公開的Trxh基因的5』端一致的序列。下劃線是方便克隆進行的NcoI限制性位點。GVR8345』GA 3』(SEQ ID NO2)粗體顯示與Rivera-Madrid等(1993)Plant Physiol 102327-328公開的Trxh基因的3』端互補的序列。下劃線為方便克隆進行的HindII限制性位點。
使用GVR833和GVR834作為引物和cDNA文庫CD4-12作為模板進行聚合酶鏈式反應(PCR)。分離得到的PCR片斷，將其克隆至pBluescript並測序。編碼Trxh的分離序列與公開的Trxh基因序列(Rivera-Madrid等(1993)Plant Physiol 102327-328)一致。含有Trxh基因的pBluescript載體被稱作pSBS2500。
為了分離硫氧還蛋白還原酶基因，合成如下引物GVR8365』GGCCAGCACACTACC 3』(SEQ ID NO3)。粗體顯示與公開的硫氧還蛋白還原酶基因的5』端一致的序列(Jacquot等，J.Mol Biol.(1994)235(4)1357-63)。GVR8375』TTAAGC 3』(SEQID NO4)。
使用GVR8336和GVR837作為引物和cDNA文庫CD4-12作為模板進行聚合酶鏈式反應(PCR)。分離得到的PCR片斷，將其克隆至pBluescript並測序。含有硫氧還蛋白還原酶基因的pBluescript載體被稱作pSBS2502。
對總共3個克隆進行測序，此3個克隆的序列均互相一致。然而，正如圖1所示，該序列顯示出與公開的硫氧還蛋白還原酶基因序列(Jacquot等，J.Mol Biol.(1994)235(4)1357-63)有幾個核苷酸差異。SEQ IDNO1中顯示了完整的編碼序列和其推導的胺基酸序列。由於公開序列和實施例1中分離的序列之間存在核苷酸差異，故也預測到幾個胺基酸改變。公開的NADPH硫氧還蛋白還原酶序列硫氧還蛋白還原酶(ATTHIREDB，Jacquot等，J Mol Biol.(1994)235(4)1357-63)的推導的胺基酸序列和實施例1(TR)分離的序列之間的比較顯示在圖3中。
實施例2植物表達載體的構建構建表達載體以允許在種子中以種子特異性方式過表達硫氧還蛋白和NADPH硫氧還蛋白還原酶。構建載體以允許在其天然亞細胞位置處實現過表達和在油體上積累。
植物轉化載體pSBS2520的構建將實施例1描述的鼠耳芥硫氧還蛋白h基因置於菜豆蛋白啟動子和菜豆蛋白終止子的調控之下，所述啟動子和終止子來源於菜豆(Phaseolusvulgaris)(Slighton等(1983)Proc.Natl Acad Sc USA 801897-1901；Sengupta-Gopalan等(1985)PNAS USA 823320-3324))。通過重疊延伸技術(Horton等(1989)1561-68)進行基因拼接，使菜豆蛋白啟動子和Trxh基因融合。利用標準分子生物學實驗室技術(見例如，Sambrook等(1990)Molecular Cloning，第2版，Cold Spring Harbor Press)以提供分別具有PstI和HindIII/KpnI位點的菜豆蛋白啟動子和終止子(見SEQ ID NO14)。再利用標準分子生物學實驗室技術將菜豆蛋白終止子置於Trxh基因下遊。將PstI-菜豆蛋白啟動子-Trxh-菜豆蛋白終止子-KpnI插入序列克隆至pSBS3000的PstI-KpnI位點中。(pSB3000是農桿菌二元質粒pPZP221(Hajdukiewicz等1994，Plant Molec.Biol.25989-994)的衍生物。在pSBS3000中，用歐芹泛素啟動子-膦絲菌素乙醯轉移酶基因-歐芹泛素終止序列代替pPZP221的CaMV35S啟動子-慶大黴素抗性基因-CAMV 35S終止子，從而賦予對除草劑草銨膦的抗性)。所獲質粒稱作pSBS2520。SEQ ID NO14中顯示了菜豆蛋白啟動子-鼠耳芥Trxh-菜豆蛋白終止序列的序列。
植物轉化載體pSBS2510的構建改變鼠耳芥油質蛋白基因(van Rooijen等(1992)Plant Mol.Biol.181177-1179)的3』編碼序列以含有NcoI位點。利用此NcoI限制性位點，使來自載體pSBS2500(實施例1)含有Trxh的NcoI-HindIII片斷與鼠耳芥油質蛋白的編碼序列連接。利用重疊延伸技術(Horton等(1989)1561-68)進行基因拼接，使含有合成的PstI位點(見pSBS2520的構建)的菜豆蛋白啟動子(Slightom等(1983)Proc.Nati Acad Sc USA 801897-1901；Sengupta-Gopalan等，(1985)PNAS USA 823320-3324)與鼠耳芥油質蛋白的編碼序列融合。再利用標準分子生物學實驗室技術(見例如Sambtook等(1990)Molecular Cloning，第2版，Cold SpringHarbor Press)克隆含有菜豆蛋白終止子的HindIII KpnI片斷(見pSBS2520的構建)位於Trxh基因下遊。將PstI-菜豆蛋白啟動子-油質蛋白-Trxh-菜豆蛋白終止子-KpnI插入序列克隆在pSBS3000的PstI-KpnI位點中。所獲質粒稱作pSBS2510。菜豆啟動子-油質蛋白Trxh-菜豆蛋白終止序列的序列顯示在SEQ ID NO16中。
植物轉化載體pSBS2521的構建除了其中的Trxh基因與油質蛋白基因的5』末端融合之外，該載體含有與pSBS2510的插入片斷相同的遺傳元件。為3』油質蛋白編碼序列(包括其天然終止密碼子)(van Rooijen等(1992)Plant Mol.Biol.181177-1179)提供HindIII克隆位點。再次，利用重疊延伸技術(Horton等(1989)1561-68)進行基因拼接，使菜豆蛋白啟動子與Trxh基因融合，並使Trxh基因與油質蛋白序列融合。再利用標準分子生物學實驗室技術(見例如，Sambrook等(1990)Molecular Cloning，第2版，Cold SpringHarbor Press)克隆含有菜豆蛋白終止子(見pSBS2520的構建)的HindIIIKpnI片斷位於油質蛋白基因下遊。將此PstI-菜豆蛋白啟動子-Trxh油質蛋白-菜豆蛋白終止子-KpnI插入序列克隆至pSBS3000的PstI-KpnI位點中。所獲質粒稱作pSBS2521。菜豆蛋白啟動子-Trxh油質蛋白-菜豆蛋白終止序列的序列顯示在SEQ ID NO19中。
植物轉化載體pSBS2527的構建將實施例1所述鼠耳芥NADPH硫氧還蛋白還原酶基因置於菜豆蛋白啟動子和菜豆蛋白終止子的調控下，所述啟動子和終止子來源於菜豆(Phaseolus vulgaris)(Slighton等(1983)Proc.Natl Acad Sc USA801897-1901；Sengupta-Gopalan等(1985)PNAS USA 823320-3324))。通過重疊延伸技術(Horton等(1989)1561-68)進行基因拼接，使菜豆蛋白啟動子和硫氧還蛋白還原酶基因融合。利用標準分子生物學實驗室技術(見例如，Sambrook等(1990)Molecular Cloning，第2版，ColdSpring Harbor Press)以提供分別具有PstI和HindIII/KpnI位點的菜豆蛋白啟動子和終止子(見SEQ ID NO14)。再利用標準分子生物學實驗室技術將菜豆蛋白終止子置於硫氧還蛋白還原酶基因下遊。將PstI-菜豆蛋白啟動子-硫氧還蛋白還原酶-菜豆蛋白終止子-KpnI插入序列克隆至pSBS3000的PstI-KpnI位點中。所獲質粒稱作pSBS2527。SEQ ID NO22中顯示了菜豆蛋白啟動子-鼠耳芥硫氧還蛋白還原酶-菜豆蛋白終止序列的序列。
植物轉化載體pSBS2531的構建利用重疊延伸技術(Horton等(1989)1561-68)進行基因拼接，使菜豆蛋白啟動子(Slightom等(1983)Proc.Nati Acad Sc USA 801897-1901；Sengupta-Gopalan等，(1985)PNAS USA 823320-3324)與鼠耳芥油質蛋白的編碼序列融合。利用相同基因拼接技術使油質蛋白基因和硫氧還蛋白還原酶編碼序列融合。利用標準分子生物學實驗室技術(見例如Sambrook等(1990)Molecular Cloning，第2版，Cold SpringHarbor Press)克隆含有菜豆蛋白的HindIII KpnI片斷位於硫氧還蛋白還原酶基因下遊。將PstI-菜豆蛋白啟動子-油質蛋白-硫氧還蛋白還原酶-菜豆蛋白終止子-KpnI插入序列克隆在pSBS3000的PstI-KpnI位點中。所獲質粒稱作pSBS2531。菜豆啟動子-油質蛋白-硫氧還蛋白還原酶-菜豆蛋白終止序列的序列顯示在SEQ ID NO24中。
植物轉化載體pSBS2529的構建除了其中的硫氧還蛋白還原酶基因與油質蛋白基因的5』末端融合之外，該載體含有與pSBS2531的插入片斷相同的遺傳元件。為3』油質蛋白編碼序列(包括其天然終止密碼子)(van Rooijen等(1992)Plant Mol.Biol.181177-1179)提供HindIII克隆位點。再次，利用重疊延伸技術(Horton等(1989)1561-68)進行基因拼接，使菜豆蛋白啟動子與硫氧還蛋白還原酶基因融合併使硫氧還蛋白還原酶基因與油質蛋白序列融合。再利用標準分子生物學實驗室技術(見例如，Sambrook等(1990)Molecular Cloning，第2版，Cold Spring Harbor Press)克隆含有菜豆蛋白終止子(見pSBS2520的構建)的HindIII KpnI片斷位於油質蛋白基因下遊。將此PstI-菜豆蛋白啟動子-硫氧還蛋白還原酶-油質蛋白-菜豆蛋白終止子-KpnI插入序列克隆至pSBS3000的PstI-KpnI位點中。所獲質粒稱作pSBS2529。菜豆蛋白啟動子-硫氧還蛋白還原酶-油質蛋白-菜豆蛋白終止序列的序列顯示在SEQ ID NO27中。
植物轉化載體pSBS2530的構建構建含有麻風分枝桿菌硫氧還蛋白還原酶/硫氧還蛋白基因(MlepTR/Trxh)的植物轉化體。從免疫血液學和血液庫系(Leiden大學，荷蘭)獲得稱作pHIS/TR/Trxh(Wieles等(1995)J Biol Chem27025604-25606)的構建體，將其用作PCR模板製備pSBS2530。pSBS2530的構建與pSBS2531的構建除了以Mlep TR/Trxh基因代替鼠耳芥硫氧還蛋白還原酶基因外均一致。利用重疊延伸技術(Horton等(1989)1561-68)進行基因拼接，使菜豆蛋白啟動子(Slightom等(1983)Proc.Nati Acad Sc USA 801897-1901；Sengupta-Gopalan等，(1985)PNASUSA 823320-3324)與鼠耳芥油質蛋白的編碼序列融合。利用相同基因拼接技術使油質蛋白基因和Mlep TR/Trxh編碼序列融合。利用標準分子生物學實驗室技術(見例如Sambrook等(1990)Molecular Cloning，第2版，Cold Spring Harbor Press)克隆含有菜豆蛋白的HindIII KpnI片斷位於Mlep TR/Trxh基因下遊。將PstI-菜豆蛋白啟動子-油質蛋白-Mlep TR/Trxh-菜豆蛋白終止子-KpnI插入序列克隆在pSBS3000的Ps1tI-KpnI位點中。所獲質粒稱作pSBS2530。菜豆啟動子-油質蛋白MlepTR/Trxh-菜豆蛋白終止序列的序列顯示在SEQ ID NO30中。
植物轉化載體pSBS2542的構建從最初活性分析(圖4)明顯地看出，表達油質蛋白-M.lep TR/Trxh融合蛋白的油體含有相當大程度的還原活性。預期編碼鼠耳芥硫氧還蛋白還原酶和硫氧還蛋白蛋白質的類似油質蛋白融合構建體也將有類似表現。利用分子模建幫助設計此構建體。設計出引物(硫氧還蛋白接頭-L5』ACTGGAGATGTTGACTCGACGGATACTACGGATTGGTCGACGGCTATGGAAGAAGGACAAGTGATCGCCTGC-3』；(SEQ ID NO5)，和硫氧還蛋白接頭-R5』-ATCCGTCGAGTCAACATCTCCA GTTTCCTCGGTGGTCTCGTTAGCCTTCGATCCAGCAATCTCTT GTAAGAATGCTCTGC-3』；(SEQ ID NO6))以編碼合成接頭肽，此肽將位於硫氧還蛋白還原酶和硫氧還蛋白之間。藉助重疊延伸技術(Horton等(1989)1561-68)進行基因拼接，利用這些引物和引物GVR873(5』-GTGGAAGCT TATGGAGATGGAG-3』；SEQ ID NO7)和GVR834(5』GAAAGCTTAAGCCAAGTGTTTG-3』；SEQ ID NO2)擴增編碼硫氧還蛋白還原酶-接頭區域-硫氧還蛋白。然後使用標準分子生物學實驗室技術(見例如Sambrook等(1990)Molecular Cloning，第2版，ColdSpring Harbor Press)，將此硫氧還蛋白還原酶-接頭-硫氧還蛋白編碼序列克隆在預製備的pSBS3000載體中。所獲質粒稱作pSBS2542。菜豆蛋白啟動子-油質蛋白-硫氧還蛋白還原酶-接頭-硫氧還蛋白-菜豆蛋白終止子區域的序列顯示在SEQ ID NO33。此鼠耳芥硫氧還蛋白還原酶-接頭-硫氧還蛋白與麻風分枝桿菌TR/Trxh蛋白之間的胺基酸序列比較顯示在圖12中。
將質粒pSBS2510，pSBS2520，pSBS2521，pSBS2527，pSBS2529，pSBS2530，pSBS2531和pSBS2542電穿孔入農桿菌菌株EHA101中。使用這些農桿菌菌株轉化鼠耳芥。除了在移植至土壤和允許結籽之後在含有80μM L-膦絲菌素的瓊脂糖平板上選擇推測的轉基因植物外，鼠耳芥的轉化基本上按「鼠耳芥操作方案分子生物學方法」第82卷，Martinez-Zapater JM和Salinas J.ISBN 0-89603-391-0，p259-266(1998)所述進行。
實施例3轉基因種子提取物的聚丙烯醯胺凝膠電泳和免疫印跡鼠耳芥(Arabidopsis)硫氧還蛋白、硫氧還蛋白還原酶和油質蛋白抗體的來源以符合閱讀框的形式將鼠耳芥硫氧還蛋白和硫氧還蛋白還原酶基因克隆在細菌表達載體pRSETB(Invitrogen)中以允許鼠耳芥硫氧還蛋白和硫氧還蛋白還原酶蛋白質過表達。這些蛋白質採用標準操作(見例如，Invitrogen操作指南)純化，並用於通過標準生物化學技術(見例如Current Protocols in Molecular Biology，John WileySons，N.Y.(1989))在兔子中產生抗體。以符合閱讀框的形式將鼠耳芥油質蛋白基因克隆在細菌表達載體pRSETB(Invitrogen)中以允許過表達鼠耳芥油質蛋白。該蛋白質採用標準操作(見例如，Invitrogen操作指南)純化，並用於通過標準生物化學技術(見例如Current Protocols in MolecularBiology，John WileySons，N.Y.(1989))製備小鼠單克隆抗體。
製備鼠耳芥屬種子總提取物用於PAGE。
在大約20倍體積的2％SDS，50mM Tris-Cl中研磨鼠耳芥種子，煮沸該提取物，離心，然後採用標準操作預備上清液用於聚丙烯醯胺凝膠電泳(PAGE)。
製備鼠耳芥油體蛋白提取物在大約20倍體積的水中研磨鼠耳芥種子，在微量離心機中離心。回收油體，相繼用大約20倍體積的水、高嚴緊性洗滌緩衝液(含有8M尿素和100mM碳酸鈉)和水洗滌。此最後一次洗滌後，採用標準操作預備油體用於聚丙烯醯胺凝膠電泳(PAGE)。
分析pSBS2510轉化的植物的種子和油體提取物將來自pSBS2510轉化的植物的種子和油體蛋白總提取物加載至聚丙烯醯胺凝膠上，用考馬斯亮蘭染色或將其電印跡至PVDF膜上。用抗鼠耳芥硫氧還蛋白的多克隆抗體、或抗鼠耳芥18.5kDa油質蛋白的單克隆抗體接觸這些膜，使用鹼性磷酸酶進行顯現。油質蛋白-硫氧還蛋白的表達導致額外的31.2kDa帶。結果表明，硫氧還蛋白抗體可以和具有正確預測分子量(31.2kDa)的帶發生免疫學反應，而且油質蛋白抗體也可以和具有此正確的預期融合蛋白分子量(31.2kDa)的帶以及相應於天然鼠耳芥油質蛋白(18.5kDa)的帶發生免疫學反應。這表明，鼠耳芥種子中表達了油質蛋白-硫氧還蛋白，而且此蛋白質被正確地導向油體。
分析pSBS2521轉化的植物的種子和油體提取物將來自pSBS2521轉化的植物的種子和油體蛋白總提取物加載至聚丙烯醯胺凝膠上，用考馬斯亮蘭染色或將其電印跡至PVDF膜上。用抗鼠耳芥硫氧還蛋白的多克隆抗體、或抗鼠耳芥18.5kDa油質蛋白的單克隆抗體接觸這些膜，使用鹼性磷酸酶進行顯現。油質蛋白-硫氧還蛋白的表達導致額外的31.2kDa帶。結果表明，硫氧還蛋白抗體可以和具有正確預測分子量(31.2kDa)的帶發生免疫學反應，而且油質蛋白抗體也可以和具有此正確的預期融合蛋白分子量(31.2kDa)的帶以及相應於天然鼠耳芥油質蛋白(18.5kDa)的帶發生免疫學反應。這表明，鼠耳芥種子中表達了硫氧還蛋白-油質蛋白，而且此蛋白質被正確地導向油體。
分析pSBS2520轉化的植物的種子提取物將來自pSBS2520轉化的植物的種子提取物加載至聚丙烯醯胺凝膠上，用考馬斯亮蘭染色或將其電印跡至PVDF膜上。用抗鼠耳芥硫氧還蛋白的多克隆抗體接觸這些膜，使用鹼性磷酸酶進行觀察。結果表明，硫氧還蛋白抗體可以和具有大約正確的預測分子量(12kDa)的帶發生免疫學反應。未轉化的種子不顯示可檢測的硫氧還蛋白帶。
分析pSBS2529轉化的植物的種子和油體提取物將來自pSBS2529轉化的植物的種子和油體蛋白總提取物加載至聚丙烯醯胺凝膠上，將其電印跡至PVDF膜上。用抗鼠耳芥硫氧還蛋白還原酶的多克隆抗體或抗鼠耳芥18.5kDa油質蛋白的單克隆抗體接觸這些膜，使用鹼性磷酸酶進行觀察。硫氧還蛋白還原酶-油質蛋白的表達導致額外的53.8kDa帶。結果表明，硫氧還蛋白還原酶抗體可以和具有正確預測的融合蛋白分子量(53.8kDa)的帶發生免疫學反應，而且油質蛋白抗體也可以和具有此正確預期分子量(53.8kDa)的帶以及相應於天然鼠耳芥油質蛋白(18.5kDa)的帶發生免疫學反應。這表明，鼠耳芥種子中表達了硫氧還蛋白還原酶-油質蛋白。
分析pSBS2527轉化的植物的種子提取物將來自pSBS2527轉化的植物的種子提取物加載至聚丙烯醯胺凝膠上，將其電印跡至PVDF膜上。用抗鼠耳芥硫氧還蛋白還原酶的多克隆抗體接觸這些膜，使用鹼性磷酸酶進行觀察。硫氧還蛋白還原酶抗體與具有大約正確的預測分子量(35.3kDa)的帶發生免疫學反應。未轉化的種子不顯示可檢測的硫氧還蛋白帶。
分析pSBS2531轉化的植物的種子提取物製備蛋白質凝膠和免疫印跡分析油質蛋白-DMSR在鼠耳芥T2種子中的表達和向鼠耳芥油體的正確導向。基於推導的胺基酸序列計算得到的預期分子量為53,817Da。在轉基因油質蛋白-硫氧還蛋白還原酶樣品的油體提取物中，觀察到額外的大約54kDa的帶。通過免疫印跡證實該帶是油質蛋白-硫氧還蛋白還原酶。從聚丙烯醯胺凝膠上，觀察到油質蛋白-硫氧還蛋白還原酶的表達是主要的18.5kDa鼠耳芥油質蛋白表達的大約兩倍。這是種子總蛋白的大約2-4％。
分析pSBS2530轉化的植物的種子提取物製備蛋白質凝膠和免疫印跡分析油質蛋白-M.lep TR/Trxh在鼠耳芥T2種子中的表達和向鼠耳芥油體的正確導向。基於推導的胺基酸序列計算得到的預期分子量為67,550Da。在轉基因油質蛋白-M.lep TR/Trxh樣品的油體提取物中，觀察到額外的大約68kDa的帶。通過免疫印跡證實該帶是油質蛋白-M.lep TR/Trxh。從聚丙烯醯胺凝膠上，觀察到油質蛋白-M.lep TR/Trxh的表達與主要的18.5kDa鼠耳芥油質蛋白的表達類似。這是種子總蛋白的大約1-2％。
分析pSBS2542轉化的植物的種子提取物通過在1mL的100mM Tris緩衝液(pH 7.5)中研磨100μg種子，從pSBS2542系製備粗油體提取物。然後離心樣品以分離油體級分。然後將油體級分加載至SDS聚丙烯醯胺凝膠上以便進行表達分析。考馬斯亮蘭揭示，在測試的4個株系的3個的粗油體提取物中合成融合物積累至高水平。估計，該融合蛋白佔種子總蛋白質的大約2-5％。而且，利用抗硫氧還蛋白抗體或抗硫氧還蛋白還原酶抗體進行的western印跡也證實，此過表達的70kDa蛋白質確實是油質蛋白-硫氧還蛋白還原酶-接頭-硫氧還蛋白。
實施例4硫氧還蛋白和硫氧還蛋白還原酶轉化體的生物學活性初始還原分析DTNB分析使用DTNB[5，5』-二巰基二(2-硝基苯甲酸)]比色測定法，確定硫氧還蛋白和硫氧還蛋白還原酶的活性。在700μl反應體積中進行該測定，所述反應體積中含有100mM Tris-Cl pH8.0、5mM EDTA、200μm DTNB[5，5』-二巰基二(2-硝基苯甲酸)]和200μM NADPH。如果加入硫氧還蛋白和硫氧還蛋白還原酶，NADPH將還原硫氧還蛋白還原酶，然後該酶將還原硫氧還蛋白，而這又導致DTNB的還原。(見如下反應式)。NADPH2+硫氧還蛋白還原酶ox----硫氧還蛋白還原酶red+NADP+硫氧還蛋白還原酶red+硫氧還蛋白ox------硫氧還蛋白red+硫氧還蛋白還原酶ox硫氧還蛋白red+DTNBox-------2(2-硝基-5-巰基苯甲酸)+硫氧還蛋白ox在規定的時間(通常0.5-2小時)後，在分光光度計中測量OD412以監測黃色產物的形成。圖4柱型圖中顯示了初始活性測定的結果，也見下述。
首先，加入100μg來自各鼠耳芥轉基因系、pSBS2520(胞質硫氧還蛋白)和pSBS2527(胞質硫氧還蛋白還原酶)的總種子蛋白，該量相應於本測試中使用的大約1μg胞質硫氧還蛋白和硫氧還蛋白還原酶。在此情況下，還原的DTNB量與各1μg大腸桿菌硫氧還蛋白和硫氧還蛋白還原酶引起的還原相當。在這些植物種子樣品中，當僅將此2種提取物中的一種(胞質硫氧還蛋白或胞質硫氧還蛋白還原酶；分別為圖4的柱3和6)和野生型油體加入反應中時背景讀數極低。
使用來自轉基因種子的油體級分進行的分析揭示，當與油體上的油質蛋白融合時，鼠耳芥硫氧還蛋白和硫氧還蛋白還原酶具有實質上較低的活性。在本測定中使用了大約300μg未洗滌的粗油體蛋白(相應於10-30μg硫氧還蛋白-油質蛋白(pSBS 2521；圖4柱2)、油質蛋白-硫氧還蛋白(pSBS 2510，圖4柱1)、硫氧還蛋白還原酶-油質蛋白(pSBS 2529，圖4柱5)或油質蛋白-硫氧還蛋白還原酶(pSBS 2531，圖4柱4))。聯合含有大約1μg胞質硫氧還蛋白(pSBS 2520)或硫氧還蛋白還原酶(pSBS2527)的100μg總種子蛋白，測試這些油體蛋白。
在此類測定中，pSBS2529(硫氧還蛋白還原酶-油質蛋白)和pSBS2531(油質蛋白-硫氧還蛋白還原酶)在與來自pSBS2520的胞質硫氧還蛋白聯合時確實含有還原酶活性(分別見圖4柱7和8)。實驗估計，油質蛋白-硫氧還蛋白還原酶的還原酶活性為胞質硫氧還蛋白還原酶活性的大約10-15％。以終濃度0.4％加入Tween可以增強該活性2或3倍。有趣的是，油質蛋白-硫氧還蛋白還原酶(pSBS2531)表現出能夠在缺少加入的硫氧還蛋白的情況下還原DTNB，但加入硫氧還蛋白可以導致顯著更大的DTNB還原(見，圖4；比較柱4W.T.(野生型)+油質蛋白-硫氧還蛋白還原酶和柱7硫氧還蛋白+油質蛋白-硫氧還蛋白還原酶)。使用pSBS2521(硫氧還蛋白-油質蛋白)或pSBS2510(油質蛋白-硫氧還蛋白)聯合來自pSBS2527的胞質硫氧還蛋白還原酶進行的實驗(分別見圖4柱10和11)表明，這些融合物的硫氧還蛋白活性在這些濃度下是檢測不到的。
來自轉基因鼠耳芥株系pSBS2530(油質蛋白-M.lep TR/Trxh)的油體含有顯著的硫氧還蛋白/硫氧還蛋白還原酶活性(見圖4柱12)。在本測定中測試了100μg來自pSBS2530的粗油體蛋白(相應於大約5μg油質蛋白-M.lep TR/Trxh融合物)。基於此測定，當比較比活性時，估計該融合物的活性為胞質鼠耳芥硫氧還蛋白和硫氧還蛋白還原酶活性(見圖4柱9)的大約25-40％。
胰島素還原試驗來自DTNB試驗的結果得到胰島素還原試驗的驗證。該試驗在100mMKH2PO4pH7.0+5mM EDTA中含有終濃度1mg/mL的胰島素。在存在NADPH(500μM)、硫氧還蛋白和硫氧還蛋白還原酶的情況下，胰島素被還原，並從溶液中沉澱出來。通常，通過在OD650測定混濁度跟蹤胰島素還原。或者，可以通過監測340nm處吸光度的降低，測量NADPH2向NADP+的轉化。
在油體存在時由於分光光度計讀數受到幹擾，兩個試驗都難於進行測量。然而，可以通過在一段規定時間後離心試管，然後確定是否存在胰島素沉澱(油體飄浮在頂部，而胰島素沉澱出小球)，獲得定量數據。或者，可以在一段規定時間後過濾樣品，然後可以測量340nm處吸光度的改變。除了觀察到pSBS2531(油質蛋白-硫氧還蛋白還原酶)僅在存在來自pSBS2520的游離硫氧還蛋白時還原胰島素外，如前述，胰島素還原試驗的結果與DTNB試驗的結果一致。
分析來自共表達油質蛋白-硫氧還蛋白和油質蛋白-硫氧還蛋白還原酶的鼠耳芥雜交株系的種子基於初始DTNB和胰島素還原試驗，顯然，混合油質蛋白-硫氧還蛋白和油質蛋白-硫氧還蛋白還原酶轉基因種子的油體導致極為有限的還原活性(注-表示油質蛋白融合物的兩種構型；即，油質蛋白-硫氧還蛋白將代表油質蛋白-硫氧還蛋白和硫氧還蛋白-油質蛋白融合物)。
為了確定同一油體中存在油質蛋白-硫氧還蛋白和油質蛋白-硫氧還蛋白還原酶是否會對這些蛋白的還原活性有正面作用，設置雜交以製備雙轉基因鼠耳芥株系。所述雜交描述在表2中。
表2

將來自鼠耳芥雜交株系的種子在PPT平板上萌發，大約2周後將幼苗轉移至土壤。在分離自幼苗的DNA上進行的PCR實驗鑑定到許多在基因組中同時含有油質蛋白-硫氧還蛋白和油質蛋白-硫氧還蛋白還原酶基因構建體的植物。
收穫這些植物的種子用於表達和活性試驗。進行Western印跡以驗證這些株系中油質蛋白-硫氧還蛋白和油質蛋白-硫氧還蛋白還原酶的表達。還進行了DTNB和胰島素還原試驗以比較單轉基因親本株系和雙轉基因後代之間的活性，結果總結在表3中。表3總結了各轉基因系的DTNB還原活性。最後2行對使用雙轉基因後代的油體和混合來自單轉基因親本系的油體進行了比較。將大腸桿菌硫氧還蛋白和硫氧還蛋白混合物的相對活性設定為100％。
表3

基於DTNB和胰島素還原試驗，明顯地，與混合來自單轉基因油質蛋白-硫氧還蛋白和油質蛋白-硫氧還蛋白還原酶株系的油體相比，在同一油體上共表達油質蛋白-硫氧還蛋白和油質蛋白-硫氧還蛋白還原酶的雙轉基因植物含有顯著更多的還原活性。此外，顯示從共表達株系得到的油體提取物比株系pSBS2530(油質蛋白-M.lep TR/Trxh)含有更多的還原活性，所述株系pSBS2530是先前鑑定的油體含有最高還原活性的株系。
這些結果提示，構建雙轉基因株系(通過雜交或通過將2個表達構建體共轉化至植物中)可能是我們解決我們的最初問題的一種手段，所述最初問題是指不能通過混合來自油質蛋白-硫氧還蛋白和油質蛋白-硫氧還蛋白還原酶單轉基因株系的油體產生還原活性.
分析表達油質蛋白-硫氧還蛋白還原酶-接頭-硫氧還蛋白的鼠耳芥pSBS2542轉基因株系的種子在DTNB和胰蛋白還原試驗中，使用前述標準操作測試4株pSBS2542系的油體提取物的還原活性。再次，含有油質蛋白-硫氧還蛋白還原酶-接頭-硫氧還蛋白蛋白質的油體提取物具有顯著的還原活性。基於這些試驗，揭示出油質蛋白-硫氧還蛋白還原酶-接頭-硫氧還蛋白合成融合蛋白比油質蛋白-M.lep TR/Trxh融合物具有更高的活性。而且，含有油質蛋白-硫氧還蛋白還原酶-接頭-硫氧還蛋白蛋白質的油體也似乎比來自共表達油質蛋白-硫氧還蛋白和油質蛋白-硫氧還蛋白還原酶的雙轉基因株系的油體具有更高的還原活性。表4中總結了比較各種硫氧還蛋白還原酶/硫氧還蛋白構建體的活性的結果。表4總結了各種轉基因株系的DTNB還原活性。表達油質蛋白-硫氧還蛋白還原酶-接頭-硫氧還蛋白的pSBS2542系含有顯著的還原活性，該活性比得上「游離」形式的鼠耳芥硫氧還蛋白和硫氧還蛋白還原酶及等價的大腸桿菌蛋白質。將大腸桿菌硫氧還蛋白和硫氧還蛋白混合物的相對活性設定為100％。
表4

比較利用NADH或NADPH作為硫氧還蛋白還原酶/硫氧還蛋白系統的輔因子(電子供體)的還原試驗按前述進行DTNB和胰島素還原試驗，但使用NADH代替NADPH在利用大腸桿菌硫氧還蛋白還原酶和硫氧還蛋白的系統中作為電子供體。由此，對利用NADH或NADPH作為大腸桿菌硫氧還蛋白還原酶/硫氧還蛋白系統的輔因子進行比較。對於DTNB試驗，反應混合物由100mM Tris-Cl緩衝液(pH8.0)中的400μM DTNB、10μg/ml大腸桿菌硫氧還蛋白和10μg/ml大腸桿菌硫氧還蛋白還原酶組成。然後按如下向此DTNB反應中加入NADH或NADPH反應A.200μM NADPH(Sigma)反應B.800μM NADH(Sigma)反應C.800μM NADH(Roche)反應D.(-)輔因子反應E.800μM NADH(無TR或Trxh)。
對於胰島素還原試驗，反應混合物由100mM磷酸鉀緩衝液(pH7.0)中的1mg/ml牛胰腺胰島素、20μg/ml大腸桿菌硫氧還蛋白和20μg/ml大腸桿菌硫氧還蛋白還原酶組成。然後按如下向反應中加入NADH或NADPH反應A.800μM NADPH(Sigma)反應B.800μM NADH(Sigma)反應C.800μM NADH(Roche)反應D.(-)輔因子反應E.2mM NADH(無TR或Trxh)。
結果表明，購買自Sigma或Roche的NADH在DTNB和胰島素還原試驗中均可以充當電子供體。然而，還原速率比使用NADPH作為輔因子時觀察到的速率低。利用NADH作為電子供體時胰島素的還原速率估計是使用NADPH時的最大速率的大約25-50％。而且，利用NADH作為電子供體時DTNB的還原速率估計是使用NADPH時的最大速率的大約5-10％。使用鼠耳芥油體上的油質蛋白-硫氧還蛋白還原酶-接頭-硫氧還蛋白融合蛋白而不是大腸桿菌硫氧還蛋白還原酶和硫氧還蛋白時觀察到相似的結果。
實施例5在植物種子細胞中製備多聚體免疫球蛋白並使用A蛋白-油質蛋白融合蛋白捕獲在油體上1-在植物種子細胞中製備多聚體免疫球蛋白為了表達含有多聚體免疫球蛋白複合物的多聚體蛋白質複合物，可以1)從表達特定抗體的細胞系，如克隆的B細胞系或雜交瘤細胞系分離編碼單個輕鏈和重鏈的cDNA序列，或2)其可以是通過分別將選定的輕鏈及重鏈可變區和可獲得的輕鏈及重鏈恆定區序列組合在一起裝配而成的重組多肽。具有特異結合性質的可變區可以通過篩選這些序列群(通常為單鏈Fv噬菌體展示文庫形式)來分離。
從已知的核酸序列和輕鏈及重鏈的來源出發，分離各鏈的成熟多肽編碼序列和分泌信號序列。信號序列可以是天然抗體序列或來源於已知的植物分泌序列(例如，來自鼠耳芥或菸草的PR序列)。可以通過標準分子生物學技術將植物分泌信號序列添加至輕鏈和重鏈成熟編碼序列上。常規使用PCR融合來產生此類修飾。將分泌信號序列包括在內，可以使輕鏈和重鏈免疫球蛋白多肽從細胞中向外定向分泌並進一步使兩條鏈裝配成多聚體免疫球蛋白複合物。為了在轉基因植物種子中實現表達，裝備如下表達盒，其包含1)在植物種子中提供表達的調節啟動子序列，2)分泌信號-輕鏈序列和3)終止轉錄的調節序列。裝配第二表達盒，其包含1)在植物種子中提供表達的調節啟動子序列，2)分泌信號-重鏈序列和3)終止轉錄的調節序列。將各抗體鍊表達盒分別地克隆至農桿菌植物轉化載體中，或合併在一個轉化載體中從而使該載體具有兩個表達盒。在兩種情況下，均將表達盒克隆在植物轉化載體中，位於劃定的左和右邊界序列之間並鄰近植物的選擇標記盒。將各植物轉化載體轉化至農桿菌中。利用獲得的農桿菌菌株感染植物組織。對轉基因植物材料進行再生並選擇可存活的轉基因植物。當利用分開的轉化載體時，使產生的表達輕鏈或重鏈序列的轉基因植物株系雜交，以產生在相同植物細胞中同時表達這兩條鏈的單植物株系。當使用含有輕鏈和重鍊表達盒的單轉化載體時，初始轉基因植物株系可在相同的植物細胞中同時產生輕鏈和重鏈序列。
2-製備展示出A蛋白的轉基因油體用於捕獲免疫球蛋白為了將免疫球蛋白捕獲和展示在油體上，對油體進行工程化以使其展示免疫球蛋白結合蛋白。在此實施例中，使用來自A蛋白的熟知抗體結合域。基於金黃色葡萄球菌(Staphylococcus aureus)的A蛋白的已知序列，設計PCR引物，從細菌A蛋白序列中分離出5個連續的Ig結合域。設計引物以便以N端或C端與油質蛋白序列融合的形式克隆A蛋白序列從而靶向油體。將A蛋白和油質蛋白之間的符合閱讀框的翻譯融合物的編碼序列克隆至用於種子特異表達的植物表達盒中。最終的表達盒由在種子中提供表達的調節啟動子序列、A蛋白-油質蛋白融合序列和終止轉錄的調節序列組成。將A蛋白-油質蛋白表達盒克隆至與農桿菌介導的植物轉化相容的植物轉化載體中。該轉化載體中，在A蛋白-油質蛋白表達盒和相鄰的植物選擇表達盒的兩側含有左和右邊界序列。使用含有該載體的農桿菌菌株感染植物組織，然後對轉基因植物材料進行再生和選擇以產生轉基因植物。
3-將多聚體免疫球蛋白捕獲並展示在展示有A蛋白的油體上在一個轉基因植物株系中產生輕鏈和重鏈多聚體免疫球蛋白複合物，並通過使A蛋白-油質蛋白融合蛋白靶向油體在油體上展示A蛋白後，可以利用至少兩種實施方案將免疫球蛋白複合物捕獲在A蛋白油體上。在第一種實施方案中，以最佳比例組合來自免疫球蛋白和A蛋白-油質蛋白表達株系的轉基因種子，然後一起研磨以在同一提取物中混合來自兩個種子株系的破碎物質。在允許通過A蛋白最大回收免疫球蛋白的條件下混合和/或溫育此合併的種子提取物。使用標準相分離技術(例如離心)分離油體級分。回收的油體級分含有來自免疫球蛋白表達株系的天然油體和來自A蛋白-油質蛋白表達株系的轉基因A蛋白油體。
在第二種實施方案中，使表達免疫球蛋白複合物和A蛋白-油質蛋白融合物的植物株系雜交，然後鑑定並繁殖表達兩種組分的單個植物株系。在此方法中，免疫球蛋白複合物和A蛋白-油質蛋白融合物在同一植物種子細胞的不同細胞區室中產生。研磨來自雙轉基因株系的種子以破碎細胞物質並混合所有細胞區室中的內容物，包括使細胞外區室中的免疫球蛋白和胞質區室中位於油體上的A蛋白-油質蛋白混合。在允許通過A蛋白最大回收免疫球蛋白的條件下混合和/或孵育此物質，然後通過相分離技術分離油體級分。回收的油體級分含有展示的A蛋白和捕獲的免疫球蛋白複合物。
實施例6以帶有油體靶向域的融合物形式製備裝配的多聚體免疫球蛋白複合物以帶有油體靶向序列(例如油質蛋白)的融合蛋白形式製備各多肽以便在油體上進行展示。已發現，天然連接的異二聚體蛋白質的各亞單位可以以分開的油質蛋白融合物的形式一起產生而仍能夠在油體表面上連接成活性異二聚體。在此實施例中，異二聚體是免疫球蛋白複合物的輕鏈和重鏈亞單位，或其衍生部分。
在油體上製備免疫球蛋白Fab複合物以符合閱讀框的融合物形式，將缺少分泌信號序列的成熟輕鏈序列和油質蛋白序列N端連接。將該融合序列裝配入種子特異性表達盒中，所述表達盒由種子特異性啟動子序列、輕鏈-油質蛋白融合序列和轉錄終止序列。將表達盒插在轉化載體的左和右邊界標誌之間，鄰近植物的選擇標記盒。使用位於農桿菌中的轉化載體感染植物並產生轉基因植物。
包含重鏈可變區和恆定區的重鏈亞單位等價構建體也以符合閱讀框的融合物形式與油質蛋白連接，並組裝入用於種子特異性表達的表達盒中。該表達盒可以是用於產生分開的轉基因株系的單獨轉化載體的一部分，或重鍊表達盒可以和輕鍊表達盒合併在一個轉化載體中。如果分別在不同的轉化載體上將重鏈和輕鍊表達盒轉化至植物中，則可以對這些獨立的植物株系進行雜交以構建能在同一植物細胞中同時表達兩個異二聚體亞單位-油質蛋白融合物的單株系。提取來自雙轉基因株系的種子，或從雙重表達載體產生的單轉基因株系的種子，以分離油體。將種子材料磨碎以釋放細胞內容物，然後通過相分離技術分離油體。輕鏈和重鏈序列作為油體蛋白融合物對油體的靶向使得免疫球蛋白複合物可以在油體表面上連接。
使用完整重鏈序列和完整輕鏈序列，或使用重鏈和輕鏈序列的可變區構建類似構型，以在油體表面裝配出不同類型的異源多聚體免疫球蛋白複合物(如異二聚體)。
因此，本發明不應受限於此處描述的具體實施方案，而應理解，一般地本發明在蛋白質表達方面具有廣泛的適用性。由於修飾方案對本領域技術人員是明了的，故本發明旨在僅受所附權利要求範圍的限制。
序列總結SEQ ID NO1-4顯示用於從鼠耳芥分離硫氧還蛋白h(Trxh)和硫氧還蛋白還原酶基因的合成引物，參見實施例1所述。
SEQ ID NO5-7顯示設計用於編碼實施例2所述硫氧還蛋白還原酶和硫氧還蛋白蛋白質之間的特定接頭肽的引物。
SEQ ID NO8、10和11顯示實施例1所述本文分離的NADPH硫氧還蛋白還原酶序列的核苷酸序列和推導的胺基酸序列。
SEQ ID NO9和11分別顯示公開的NADPH硫氧還蛋白還原酶序列(ATTHIREDB)的核苷酸序列和推導的胺基酸序列。
SEQ ID NO12顯示公開的NADPH硫氧還蛋白還原酶序列的推導的胺基酸序列。
SEQ ID NO13顯示本報導中分離的NADPH還原酶序列的推導的胺基酸序列。
SEQ ID NO14和15顯示實施例2中所述菜豆蛋白啟動子-鼠耳芥Trxh-菜豆蛋白終止序列的核苷酸序列和推導的胺基酸序列。其中指出了Trxh編碼序列和其推導的胺基酸序列。菜豆蛋白啟動子相應於第6-1554位核苷酸，而菜豆蛋白終止子相應於第1905-3124位核苷酸。為啟動子提供了Pst1位點(nt 1-6)，而為終止子提供了HindIII位點(nt1898-1903)及KpnI位點(nt 3124-3129)以利於克隆。
SEQ ID NO16、17和18顯示實施例2所述菜豆蛋白啟動子-油質蛋白Trxh-菜豆蛋白終止序列的核苷酸序列和推導的胺基酸序列。SEQ ID NO16中顯示了油質蛋白-Trxh的編碼序列和推導的胺基酸序列。在SEQ IDNO14中，菜豆蛋白啟動子相應於第6-1554位核苷酸。編碼油質蛋白的序列相應於nt 1555-2313，該序列中的內含子(nt 1908-2147)以斜體顯示。Trxh編碼序列相應於nt 2314-2658。菜豆蛋白終止子相應於第2664-3884位核苷酸序列。
SEQ ID NO19、20和21顯示實施例2所述菜豆蛋白啟動子-Trxh油質蛋白-菜豆蛋白終止序列的核苷酸序列和推導的胺基酸序列。SEQ IDNO19中顯示了Trxh-油質蛋白的編碼序列和其推導的胺基酸序列。在SEQ ID NO14和16中，菜豆蛋白啟動子相應於第6-1554位核苷酸。Trxh編碼序列相應於nt 1555-1896。編碼油質蛋白的序列相應於nt1897-2658，該序列中的內含子(nt 2250-2489)以斜體表示。菜豆蛋白終止子相應於第2664-3884位核苷酸序列。
SEQ ID NO22和23顯示實施例2所述菜豆蛋白啟動子-硫氧還蛋白還原酶-菜豆蛋白終止序列的核苷酸序列和推導的胺基酸序列。SEQ ID NO22中顯示了硫氧還蛋白還原酶的編碼序列和其推導的胺基酸序列。菜豆蛋白啟動子相應於第6-1554位核苷酸。硫氧還蛋白還原酶編碼序列相應於nt 1555-2556，推導的胺基酸序列顯示在SEQ ID NO23中。菜豆蛋白終止子相應於第2563-3782位核苷酸序列。
SEQ ID NO24、25和26顯示實施例2所述菜豆蛋白啟動子-油質蛋白-硫氧還蛋白還原酶-菜豆蛋白終止序列的核苷酸序列和推導的胺基酸序列。其中顯示了油質蛋白-硫氧還蛋白還原酶的編碼序列和其推導的胺基酸序列。菜豆蛋白啟動子相應於第6-1554位核苷酸。編碼油質蛋白的序列相應於nt 1555-2313，該序列中的內含子(nt 1980-2147)以斜體表示。硫氧還蛋白還原酶編碼序列相應於nt 2314-3315。菜豆蛋白終止子相應於第3321-4540位核苷酸序列。
SEQ ID NO27、28和29顯示實施例2所述菜豆蛋白啟動子-硫氧還蛋白還原酶-油質蛋白-菜豆蛋白終止序列的核苷酸序列和推導的胺基酸序列。其中顯示了硫氧還蛋白還原酶的編碼序列和其推導的胺基酸序列。菜豆蛋白啟動子相應於第6-1554位核苷酸。硫氧還蛋白還原酶編碼序列相應於nt 1555-2553。編碼油質蛋白的序列相應於nt 2554-3315，該序列中的內含子(nt 2751-3146)以斜體表示。菜豆蛋白終止子相應於第3321-4540位核苷酸序列。
SEQ ID NO30、31和32顯示實施例2所述菜豆蛋白啟動子-油質蛋白-Mlep硫氧還蛋白還原酶/硫氧還蛋白-菜豆蛋白終止序列的核苷酸序列和推導的胺基酸序列。其中顯示了油質蛋白-Mlep硫氧還蛋白還原酶/硫氧還蛋白的編碼序列和其推導的胺基酸序列。菜豆蛋白啟動子相應於第6-1554位核苷酸。編碼油質蛋白的序列相應於nt 1555-2313，該序列中的內含子(nt)以斜體表示。Mlep硫氧還蛋白還原酶/硫氧還蛋白編碼序列相應於nt 2314-3690。菜豆蛋白終止子相應於第3698-4917位核苷酸序列。
SEQ ID NO33、34和35顯示pSBS2542中菜豆蛋白啟動子-油質蛋白-硫氧還蛋白還原酶-接頭-硫氧還蛋白-菜豆蛋白終止子區域的核苷酸序列和推導的胺基酸序列。SEQ ID NO33中還顯示了油質蛋白-硫氧還蛋白還原酶-接頭-硫氧還蛋白的推導的胺基酸序列。第1-173位顯示了表示油質蛋白的胺基酸，在第174-501位顯示了表示硫氧還蛋白還原酶的胺基酸，在第501-524位顯示了表示接頭或間隔肽的胺基酸，而在第525-636位顯示了表示硫氧還蛋白的胺基酸序列。
SEQ ID NO38和39分別顯示鼠耳芥(Arabidopsis Thaliana)硫氧還蛋白h(Trx h1)的核苷酸序列和編碼的蛋白質。
SEQ ID NO40和41分別顯示鼠耳芥(Arabidopsis Thaliana)硫氧還蛋白還原酶(NTR1)的核苷酸序列和編碼的蛋白質。
SEQ ID NO42和43分別顯示大腸桿菌硫氧還蛋白(TrxA)的核苷酸序列和編碼的蛋白質。
SEQ ID NO44和45分別顯示大腸桿菌硫氧還蛋白還原酶的核苷酸序列和編碼的蛋白質。
SEQ ID NO46和47分別顯示人硫氧還蛋白的核苷酸序列和編碼的蛋白質。
SEQ ID NO48和49分別顯示人硫氧還蛋白還原酶的核苷酸序列和編碼的蛋白質。
SEQ ID NO50和51分別顯示麻風分枝桿菌硫氧還蛋白-硫氧還蛋白還原酶的核苷酸序列和編碼的蛋白質。
SEQ ID NO52-313描述於表5中。
表5



















序列表110semBiosys Genetics，Inc.
syngenta Participations AG120製備多聚體蛋白質的方法和相關的組合物13038814-351PC140Not Yet Assigned141Herewith160313170FastSEQ for Windows Version 4.0210121122212DNA213人工序列220223引物4001taccatggct tcggaagaag ga 22210221122212DNA213人工序列220223引物4002gaaagcttaa gccaagtgtt tg22210321136212DNA213人工序列220223引物4003ggccagcaca ctaccatgaa tggtctcgaa actcac 36210421128212DNA213人工序列220223引物4004ttaagcttca atcactctta ccttgctg 28210521172212DNA213人工序列220223引物4005actggagatg ttgactcgac ggatactacg gattggtcga cggctatgga agaaggacaa 60gtgatcgcct gc 72210621180212DNA213人工序列220223引物4006atccgtcgag tcaacatctc cagtttcctc ggtggtctcg ttagccttcg atccagcaat 60ctcttgtaag aatgctctgc 80210721122212DNA213人工序列220223引物4007gtggaagctt atggagatgg ag 2221082111002212DNA213人工序列220223嵌合4008atgaatggtc tcgaaactca caacacaagg ctctgtatcg taggaagtgg cccagcggca 60cacacggcgg cgatttacgc agctagggct gaacttaaac ctcttctctt cgaaggatgg 120atggctaacg acatcgctcc cggtggtcaa ctaacaacca ccaccgacgt cgagaatttc 180cccggatttc cagaaggtat tctcggagta gagctcactg acaaattccg taaacaatcg 240gagcgattcg gtactacgat atttacagag acggtgacga aagtcgattt ctcttcgaaa 300ccgtttaagc tattcacaga ttcaaaagcc attctcgctg acgctgtgat tctcgctact 360ggagctgtgg ctaagcggct tagcttcgtt ggatctggtg aaggttctgg aggtttctgg 420aaccgtggaa tctccgcttg tgctgtttgc gacggagctg ctccgatatt ccgtaacaaa 480cctcttgcgg tgatcggtgg aggcgattca gcaatggaag aagcaaactt tcttacaaaa 540tatggatcta aagtgtatat aatccatagg agagatgctt ttagagcgtc taagattatg 600cagcagcgag ctttgtctaa tcctaagatt gatgtgattt ggaactcgtc tgttgtggaa 660gcttatggag atggagaaag agatgtgctt ggaggattga aagtgaagaa tgtggttacc 720ggagatgttt ctgatttaaa agtttctgga ttgttctttg ctattggtca tgagccagct 780accaagtttt tggatggtgg tgttgagtta gattcggatg gttatgttgt cacgaagcct 840ggtactacac agactagcgt tcccggagtt ttcgctgcgg gtgatgttca ggataagaag 900tataggcaag ccatcactgc tgcaggaact gggtgcatgg cagctttgga tgcagagcat 960tacttacaag agattggatc tcagcaaggt aagagtgatt ga10022109211999212DNA213鼠耳芥(Arabidopsis thaliana)4009atgaatggtc tcgaaactca caacacaagg ctctgtatcg taggaagtgg cccagcggca 60cacacggcgg cgatttacgc agctagggct gaacttaaac ctcttctctt cgaaggatgg 120atggctaacg acatcgctcc cggtggtcaa ctcaaccaac caccgcgtga gaatttcccc 180ggatttccag aaggtattct cggagtagag ctcactgaca aattccgtaa acaatcggag 240cgattcggta ctacgatatt tacagagacg gtgacgaaag tcgatttctc ttcgaaaccg 300tttaagctat tcacagattc aaaagccatt ctcgctgacg ctgtgattct cgctatcgga 360gctgtggcta agtggcttag cttcgttgga tctggtgaag ttctcggagg tttgtggaac 420cgtggaatct ccgcttgtgc tgtttgcgac ggagctgctc cgatattccg caacaaacct 480cttgcggtga tcggtggagg cgattctgca atggaagaag caaactttct tacaaaatat 540ggatctaaag tgtatataat cgataggaga gatgctttta gagcgtctaa gattatgcag 600cagcgagctt tgtctaatcc taagattgat gtgatttgga actcgtctgt tgtggaagct 660tatggagatg gagaaagaga tgtgcttgga ggattgaaag tgaagaatgt ggttaccgga 720gatgtttctg atttaaaagt ttctggattg ttctttgcta ttggtcatga gccagctacc 780aagtttttgg atggtggtgt tgagttagat tcggatggtt atgttgtcac gaagcctggt 840actacacaga ctagcgttcc cggagttttc gctgcgggtg atgttcagga taagaagtat 900aggcaagcca tcactgctgc aggaactggg tgcatggcag ctttggatgc agagcattac 960ttacaagaga ttggatctca gcaaggtaag agtgattga999210102111002212DNA213人工序列220223嵌合221CDS222(1)...(1002)223編碼NADPH硫氧還蛋白還原酶的cDNA40010atg aat ggt ctc gaa act cac aac aca agg ctc tgt atc gta gga agt 48Met Asn Gly Leu Glu Thr His Asn Thr Arg Leu Cys Ile Val Gly Ser1 5 10 15ggc cca gcg gca cac acg gcg gcg att tac gca gct agg gct gaa ctt 96Gly Pro Ala Ala His Thr Ala Ala Ile Tyr Ala Ala Arg Ala Glu Leu20 25 30aaa cct ctt ctc ttc gaa gga tgg atg gct aac gac atc gct ccc ggt 144Lys Pro Leu Leu Phe Glu Gly Trp Met Ala Asn Asp Ile Ala Pro Gly35 40 45ggt caa cta aca acc acc acc gac gtc gag aat ttc ccc gga ttt cca 192Gly Gln Leu Thr Thr Thr Thr Asp Val Glu Asn Phe Pro Gly Phe Pro50 55 60gaa ggt att ctc gga gta gag ctc act gac aaa ttc cgt aaa caa tcg 240Glu Gly Ile Leu Gly Val Glu Leu Thr Asp Lys Phe Arg Lys Gln Ser65 70 75 80gag cga ttc ggt act acg ata ttt aca gag acg gtg acg aaa gtc gat 288Glu Arg Phe Gly Thr Thr Ile Phe Thr Glu Thr Val Thr Lys Val Asp85 90 95ttc tct tcg aaa ccg ttt aag cta ttc aca gat tca aaa gcc att ctc 336Phe Ser Ser Lys Pro Phe Lys Leu Phe Thr Asp Ser Lys Ala Ile Leu100 105 110gct gac gct gtg att ctc gct act gga gct gtg gct aag cgg ctt agc 384Ala Asp Ala Val Ile Leu Ala Thr Gly Ala Val Ala Lys Arg Leu Ser115 120 125ttc gtt gga tct ggt gaa ggt tct gga ggt ttc tgg aac cgt gga atc 432Phe Val Gly Ser Gly Glu Gly Ser Gly Gly Phe Trp Asn Arg Gly Ile130 135 140tcc gct tgt gct gtt tgc gac gga gct gct ccg ata ttc cgt aac aaa 480Ser Ala Cys Ala Val Cys Asp Gly Ala Ala Pro Ile Phe Arg Asn Lys145 150 155 160cct ctt gcg gtg atc ggt gga ggc gat tca gca atg gaa gaa gca aac 528Pro Leu A la Val Ile Gly Gly Gly Asp Ser Ala Met Glu Glu Ala Asn165 170 175ttt ctt aca aaa tat gga tct aaa gtg tat ata atc cat agg aga gat 576Phe Leu Thr Lys Tyr Gly Ser Lys Val Tyr Ile Ile His Arg Arg Asp180 185 190gct ttt aga gcg tct aag att atg cag cag cga gct ttg tct aat cct 624Ala Phe Arg Ala Ser Lys Ile Met Gln Gln Arg Ala Leu Ser Asn Pro195 200 205aag att gat gtg att tgg aac tcg tct gtt gtg gaa gct tat gga gat 672Lys Ile Asp Val Ile Trp Asn Ser Ser Val Val Glu Ala Tyr Gly Asp210 215 220gga gaa aga gat gtg ctt gga gga ttg aaa gtg aag aat gtg gtt acc 720Gly Glu Arg Asp Val Leu Gly Gly Leu Lys Val Lys Asn Val Val Thr225 230 235 240gga gat gtt tct gat tta aaa gtt tct gga ttg ttc ttt gct att ggt 768Gly Asp Val Ser Asp Leu Lys Val Ser Gly Leu Phe Phe Ala Ile Gly245 250 255cat gag cca gct acc aag ttt ttg gat ggt ggt gtt gag tta gat tcg 816His Glu Pro Ala Thr Lys Phe Leu Asp Gly Gly Val Glu Leu Asp Ser260 265 270gat ggt tat gtt gtc acg aag cct ggt act aca cag act agc gtt ccc 864Asp Gly Tyr Val Val Thr Lys Pro Gly Thr Thr Gln Thr Ser Val Pro275 280 285gga gtt ttc gct gcg ggt gat gtt cag gat aag aag tat agg caa gcc 912Gly Val Phe Ala Ala Gly Asp Val Gln Asp Lys Lys Tyr Arg Gln Ala290 295 300atc act gct gca gga act ggg tgc atg gca gct ttg gat gca gag cat 960Ile Thr Ala Ala Gly Thr Gly Cys Met Ala Ala Leu Asp Ala Glu His305 310 315 320tac tta caa gag att gga tct cag caa ggt aag agt gat tga 1002Tyr Leu Gln Glu Ile Gly Ser Gln Gln Gly Lys Ser Asp *325 330210 11211 333212 PRT213人工序列220223嵌合40011Met Asn Gly Leu Glu Thr His Asn Thr Arg Leu Cys Ile Val Gly Ser1 5 10 15Gly Pro Ala Ala His Thr Ala Ala Ile Tyr Ala Ala Arg Ala Glu Leu20 25 30Lys Pro Leu Leu Phe Glu Gly Trp Met Ala Asn Asp Ile Ala Pro Gly35 40 45Gly Gln Leu Thr Thr Thr Thr Asp Val Glu Asn Phe Pro Gly Phe Pro50 55 60Glu Gly Ile Leu Gly Val Glu Leu Thr Asp Lys Phe Arg Lys Gln Ser65 70 75 80Glu Arg Phe Gly Thr Thr Ile Phe Thr Glu Thr Val Thr Lys Val Asp85 90 95Phe Ser Ser Lys Pro Phe Lys Leu Phe Thr Asp Ser Lys Ala Ile Leu
100 105 110Ala Asp Ala Val Ile Leu Ala Thr Gly Ala Val Ala Lys Arg Leu Ser115 120 125Phe Val Gly Ser Gly Glu Gly Ser Gly Gly Phe Trp Asn Arg Gly Ile130 135 140Ser Ala Cys Ala Val Cys Asp Gly Ala Ala Pro Ile Phe Arg Asn Lys145 150 155 160Pro Leu Ala Val Ile Gly Gly Gly Asp Ser Ala Met Glu Glu Ala Asn165 170 175Phe Leu Thr Lys Tyr Gly Ser Lys Val Tyr Ile Ile His Arg Arg Asp180 185 190Ala Phe Arg Ala Ser Lys Ile Met Gln Gln Arg Ala Leu Ser Asn Pro195 200 205Lys Ile Asp Val Ile Trp Asn Ser Ser Val Val Glu Ala Tyr Gly Asp210 215 220Gly Glu Arg Asp Val Leu Gly Gly Leu Lys Val Lys Asn Val Val Thr225 230 235 240Gly Asp Val Ser Asp Leu Lys Val Ser Gly Leu Phe Phe Ala Ile Gly245 250 255His Glu Pro Ala Thr Lys Phe Leu Asp Gly Gly Val Glu Leu Asp Ser260 265 270Asp Gly Tyr Val Val Thr Lys Pro Gly Thr Thr Gln Thr Ser Val Pro275 280 285Gly Val Phe Ala Ala Gly Asp Val Gln Asp Lys Lys Tyr Arg Gln Ala290 295 300Ile Thr Ala Ala Gly Thr Gly Cys Met Ala Ala Leu Asp Ala Glu His305 310 315 320Tyr Leu Gln Glu Ile Gly Ser Gln Gln Gly Lys Ser Asp325 33021012211332212PRT213鼠耳芥40012Met Asn Gly Leu Glu Thr His Asn Thr Arg Leu Cys Ile Val Gly Ser15 10 15Gly Pro Ala Ala His Thr Ala Ala Ile Tyr Ala Ala Arg Ala Glu Leu20 25 30Lys Pro Leu Leu Phe Glu Gly Trp Met Ala Asn Asp Ile Ala Pro Gly35 40 45Gly Gln Leu Asn Gln Pro Pro Arg Glu Asn Phe Pro Gly Phe Pro Glu50 55 60Gly Ile Leu Gly Val Glu Leu Thr Asp Lys Phe Arg Lys Gln Ser Glu65 70 75 80Arg Phe Gly Thr Thr Ile Phe Thr Glu Thr Val Thr Lys Val Asp Phe85 90 95Ser Ser Lys Pro Phe Lys Leu Phe Thr Asp Ser Lys Ala Ile Leu Ala100 105 110Asp Ala Val Ile Leu Ala Ile Gly Ala Val Ala Lys Trp Leu Ser Phe115 120 125Val Gly Ser Gly Glu Val Leu Gly Gly Leu Trp Asn Arg Gly Ile Ser130 135 140Ala Cys Ala Val Cys Asp Gly Ala Ala Pro Ile Phe Arg Asn Lys Pro145 150 155 160Leu Ala Val Ile Gly Gly Gly Asp Ser Ala Met Glu Glu Ala Asn Phe165 170 175Leu Thr Lys Tyr Gly Ser Lys Val Tyr Ile Ile Asp Arg Arg Asp Ala180 185 190Phe Arg Ala Ser Lys Ile Met Gln Gln Arg Ala Leu Ser Asn Pro Lys195 200 205Ile Asp Val Ile Trp Asn Ser Ser Val Val Glu Ala Tyr Gly Asp Gly210 215 220Glu Arg Asp Val Leu Gly Gly Leu Lys Val Lys Asn Val Val Thr Gly225 230 235 240Asp Val Ser Asp Leu Lys Val Ser Gly Leu Phe Phe Ala Ile Gly His245 250 255Glu Pro Ala Thr Lys Phe Leu Asp Gly Gly Val Glu Leu Asp Ser Asp260 265 270Gly Tyr Val Val Thr Lys Pro Gly Thr Thr Gln Thr Ser Val Pro Gly275 280 285Val Phe Ala Ala Gly Asp Val Gln Asp Lys Lys Tyr Arg Gln Ala Ile290 295 300Thr Ala Ala Gly Thr Gly Cys Met Ala Ala Leu Asp Ala Glu His Tyr305 310 315 320Leu Gln Glu Ile Gly Ser Gln Gln Gly Lys Ser Asp325 33021013211333212PRT213人工序列220223嵌合40013Met Asn Gly Leu Glu Thr His Asn Thr Arg Leu Cys Ile Val Gly Ser1 5 10 15Gly Pro Ala Ala His Thr Ala Ala Ile Tyr Ala Ala Arg Ala Glu Leu20 25 30Lys Pro Leu Leu Phe Glu Gly Trp Met Ala Asn Asp Ile Ala Pro Gly35 40 45Gly Gln Leu Thr Thr Thr Thr Asp Val Glu Asn Phe Pro Gly Phe Pro50 55 60Glu Gly Ile Leu Gly Val Glu Leu Thr Asp Lys Phe Arg Lys Gln Ser65 70 75 80Glu Arg Phe Gly Thr Thr Ile Phe Thr Glu Thr Val Thr Lys Val Asp85 90 95Phe Ser Ser Lys Pro Phe Lys Leu Phe Thr Asp Ser Lys Ala Ile Leu100 105 110Ala Asp Ala Val Ile Leu Ala Thr Gly Ala Val Ala Lys Arg Leu Ser115 120 125Phe Val Gly Ser Gly Glu Gly Ser Gly Gly Phe Trp Asn Arg Gly Ile130 135 140Ser Ala Cys Ala Val Cys Asp Gly Ala Ala Pro Ile Phe Arg Asn Lys145 150 155 160Pro Leu Ala Val Ile Gly Gly Gly Asp Ser Ala Met Glu Glu Ala Asn165 170 175Phe Leu Thr Lys Tyr Gly Ser Lys Val Tyr Ile Ile His Arg Arg Asp180 185 190Ala Phe Arg Ala Ser Lys Ile Met Gln Gln Arg Ala Leu Ser Asn Pro195 200 205Lys Ile Asp Val Ile Trp Asn Ser Ser Val Val Glu Ala Tyr Gly Asp210 215 220Gly Glu Arg Asp Val Leu Gly Gly Leu Lys Val Lys Asn Val Val Thr225 230 235 240Gly Asp Val Ser Asp Leu Lys Val Ser Gly Leu Phe Phe Ala Ile Gly245 250 255His Glu Pro Ala Thr Lys Phe Leu Asp Gly Gly Val Glu Leu Asp Ser260 265 270Asp Gly Tyr Val Val Thr Lys Pro Gly Thr Thr Gln Thr Ser Val Pro275 280 285Gly Val Phe Ala Ala Gly Asp Val Gln Asp Lys Lys Tyr Arg Gln Ala290 295 300Ile Thr Ala Ala Gly Thr Gly Cys Met Ala Ala Leu Asp Ala Glu His305 310 315 320Tyr Leu Gln Glu Ile Gly Ser Gln Gln Gly Lys Ser Asp325 330210142113129212DNA213人工序列220221CDS222(1555)...(1899)223嵌合40014ctgcaggaat tcattgtact cccagtatca ttatagtgaa agttttggct ctctcgccgg 60tggtttttta cctctattta aaggggtttt ccacctaaaa attctggtat cattctcact 120ttacttgtta ctttaatttc tcataatctt tggttgaaat tatcacgctt ccgcacacga 180tatccctaca aatttattat ttgttaaaca ttttcaaacc gcataaaatt ttatgaagtc 240ccgtctatct ttaatgtagt ctaacatttt catattgaaa tatataattt acttaatttt 300agcgttggta gaaagcataa tgatttattc ttattcttct tcatataaat gtttaatata 360caatataaac aaattcttta ccttaagaag gatttcccat tttatatttt aaaaatatat 420ttatcaaata tttttcaacc acgtaaatct cataataata agttgtttca aaagtaataa 480aatttaactc cataattttt ttattcgact gatcttaaag caacacccag tgacacaact 540agccattttt ttctttgaat aaaaaaatcc aattatcatt gtattttttt tatacaatga 600aaatttcacc aaacaatcat ttgtggtatt tctgaagcaa gtcatgttat gcaaaattct 660ataattccca tttgacacta cggaagtaac tgaagatctg cttttacatg cgagacacat 720cttctaaagt aattttaata atagttacta tattcaagat ttcatatatc aaatactcaa 780tattacttct aaaaaattaa ttagatataa ttaaaatatt acttttttaa ttttaagttt 840aattgttgaa tttgtgacta ttgatttatt attctactat gtttaaattg ttttatagat 900agtttaaagt aaatataagt aatgtagtag agtgttagag tgttacccta aaccataaac 960tataagattt atggtggact aattttcata tatttcttat tgcttttacc ttttcttggt 1020atgtaagtcc gtaactggaa ttactgtggg ttgccatggc actctgtggt cttttggttc 1080atgcatggat gcttgcgcaa gaaaaagaca aagaacaaag aaaaaagaca aaacagagag 1140acaaaacgca atcacacaac caactcaaat tagtcactgg ctgatcaaga tcgccgcgtc 1200catgtatgtc taaatgccat gcaaagcaac acgtgcttaa catgcacttt aaatggctca 1260cccatctcaa cccacacaca aacacattgc ctttttcttc atcatcacca caaccacctg 1320tatatattca ttctcttccg ccacctcaat ttcttcactt caacacacgt caacctgcat 1380atgcgtgtca tcccatgccc aaatctccat gcatgttcca accaccttct ctcttatata 1440atacctataa atacctctaa tatcactcac ttctttcatc atccatccat ccagagtact 1500actactctac tactataata ccccaaccca actcatattc aatactactc tact atg 1557Met1gct tcg gaa gaa gga caa gtg atc gcc tgc cac acc gtt gag aca tgg 1605Ala Ser Glu Glu Gly Gln Val Ile Ala Cys His Thr Val Glu Thr Trp5 10 15aac gag cag ctt cag aag gct aat gaa tcc aaa act ctt gtg gtg gtt 1653Asn Glu Gln Leu Gln Lys Ala Asn Glu Ser Lys Thr Leu Val Val Val20 25 30gat ttc acg gct tct tgg tgt gga cca tgt cgt ttc atc gct cca ttc 1701Asp Phe Thr Ala Ser Trp Cys Gly Pro Cys Arg Phe Ile Ala Pro Phe35 40 45ttt gct gat ttg gct aag aaa ctt cct aac gtg ctt ttc ctc aag gtt 1749Phe Ala Asp Leu Ala Lys Lys Leu Pro Asn Val Leu Phe Leu Lys Val50 55 60 65gat act gat gaa ttg aag tcg gtg gca agt gat tgg gcg ata cag gcg 1797Asp Thr Asp Glu Leu Lys Ser Val Ala Ser Asp Trp Ala Ile Gln Ala70 75 80atg cca acc ttc atg ttt ttg aag gaa ggg aag att ttg gac aaa gtt 1845Met Pro Thr Phe Met Phe Leu Lys Glu Gly Lys Ile Leu Asp Lys Val85 90 95gtt gga gcc aag aaa gat gag ctt cag tct acc att gcc aaa cac ttg 1893Val Gly Ala Lys Lys Asp Glu Leu Gln Ser Thr Ile Ala Lys His Leu
100 105 110gct taa gcttaataag tatgaactaa aatgcatgta ggtgtaagag ctcatggaga1949Ala *gcatggaata ttgtatccga ccatgtaaca gtataataac tgagctccat ctcacttctt 2009ctatgaataa acaaaggatg ttatgatata ttaacactct atctatgcac cttattgttc 2069tatgataaat ttcctcttat tattataaat catctgaatc gtgacggctt atggaatgct 2129tcaaatagta caaaaacaaa tgtgtactat aagactttct aaacaattct aactttagca 2189ttgtgaacga gacataagtg ttaagaagac ataacaatta taatggaaga agtttgtctc 2249catttatata ttatatatta cccacttatg tattatatta ggatgttaag gagacataac 2309aattataaag agagaagttt gtatccattt atatattata tactacccat ttatatatta 2369tacttatcca cttatttaat gtctttataa ggtttgatcc atgatatttc taatatttta 2429gttgatatgt atatgaaagg gtactatttg aactctctta ctctgtataa aggttggatc 2489atccttaaag tgggtctatt taattttatt gcttcttaca gataaaaaaa aaattatgag 2549ttggtttgat aaaatattga aggatttaaa ataataataa ataataaata acarataara 2609tatgtatata aatttattat aatataacat ttatctataa aaaagtaaat attgtcataa 2669atctatacaa tcgtttagcc ttgctggacg actctcaatt atttaaacga gagtaaacat 2729atttgacttt ttggttattt aacaaattat tatttaacac tatatgaaat tttttttttt 2789tatcggcaag gaaataaaat taaattagga gggacaatgg tgtgtcccaa tccttataca 2849accaacttcc acaggaaggt caggtcgggg acaacaaaaa aacaggcaag ggaaattttt 2909taatttgggt tgtcttgttt gctgcataat ttatgcagta aaacactaca cataaccctt 2969ttagcagtag agcaatggtt gaccgtgtgc ttagcttctt ttattttatt tttttatcag 3029caaagaataa ataaaataaa atgagacact tcagggatgt ttcaaccctt atacaaaacc 3089ccaaaaacaa gtttcctagc accctaccaa ctaaggtacc 312921015211114212PRT213人工序列220223嵌合400 15Met Ala Ser Glu Glu Gly Gln Val Ile Ala Cys His Thr Val Glu Thr1 5 10 15Trp Asn Glu Gln Leu Gln Lys Ala Asn Glu Ser Lys Thr Leu Val Val20 25 30Val Asp Phe Thr Ala Ser Trp Cys Gly Pro Cys Arg Phe Ile Ala Pro35 40 45Phe Phe Ala Asp Leu Ala Lys Lys Leu Pro Asn Val Leu Phe Leu Lys50 55 60Val Asp Thr Asp Glu Leu Lys Ser Val Ala Ser Asp Trp Ala Ile Gln65 70 75 80Ala Met Pro Thr Phe Met Phe Leu Lys Glu Gly Lys Ile Leu Asp Lys85 90 95Val Val Gly Ala Lys Lys Asp Glu Leu Gln Ser Thr Ile Ala Lys His100 105 110Leu Ala210162113888212DNA213人工序列220223嵌合221CDS222(1555)...(1907)221CDS222(2148)...(2659)40016ctgcaggaat tcattgtact cccagtatca ttatagtgaa agttttggct ctctcgccgg 60tggtttttta cctctattta aaggggtttt ccacctaaaa attctggtat cattctcact 120ttacttgtta ctttaatttc tcataatctt tggttgaaat tatcacgctt ccgcacacga 180tatccctaca aatttattat ttgttaaaca ttttcaaacc gcataaaatt ttatgaagtc 240ccgtctatct ttaatgtagt ctaacatttt catattgaaa tatataattt acttaatttt 300agcgttggta gaaagcataa tgatttattc ttattcttct tcatataaat gtttaatata 360caatataaac aaattcttta ccttaagaag gatttcccat tttatatttt aaaaatatat 420ttatcaaata tttttcaacc acgtaaatct cataataata agttgtttca aaagtaataa 480aatttaactc cataattttt ttattcgact gatcttaaag caacacccag tgacacaact 540agccattttt ttctttgaat aaaaaaatcc aattatcatt gtattttttt tatacaatga 600aaatttcacc aaacaatcat ttgtggtatt tctgaagcaa gtcatgttat gcaaaattct 660ataattccca tttgacacta cggaagtaac tgaagatctg cttttacatg cgagacacat 720cttctaaagt aattttaata atagttacta tattcaagat ttcatatatc aaatactcaa 780tattacttct aaaaaattaa ttagatataa ttaaaatatt acttttttaa ttttaagttt 840aattgttgaa tttgtgacta ttgatttatt attctactat gtttaaattg ttttatagat 900agtttaaagt aaatataagt aatgtagtag agtgttagag tgttacccta aaccataaac 960tataagattt atggtggact aattttcata tatttcttat tgcttttacc ttttcttggt 1020atgtaagtcc gtaactggaa ttactgtggg ttgccatggc actctgtggt cttttggttc 1080atgcatggat gcttgcgcaa gaaaaagaca aagaacaaag aaaaaagaca aaacagagag 1140acaaaacgca atcacacaac caactcaaat tagtcactgg ctgatcaaga tcgccgcgtc 1200catgtatgtc taaatgccat gcaaagcaac acgtgcttaa catgcacttt aaatggctca 1260cccatctcaa cccacacaca aacacattgc ctttttcttc atcatcacca caaccacctg 1320tatatattca ttctcttccg ccacctcaat ttcttcactt caacacacgt caacctgcat 1380atgcgtgtca tcccatgccc aaatctccat gcatgttcca accaccttct ctcttatata 1440atacctataa atacctctaa tatcactcac ttctttcatc atccatccat ccagagtact 1500actactctac tactataata ccccaaccca actcatattc aatactactc tact atg 1557Met1gcg gat aca gct aga gga acc cat cac gat atc atc ggc aga gac cag 1605Ala Asp Thr Ala Arg Gly Thr His His Asp Ile Ile Gly Arg Asp Gln5 10 15tac ccg atg atg ggc cga gac cga gac cag tac cag atg tcc gga cga 1653Tyr Pro Met Met Gly Arg Asp Arg Asp Gln Tyr Gln Met Ser Gly Arg20 25 30gga tct gac tac tcc aag tct agg cag att gct aaa gct gca act gct 1701Gly Ser Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala Ala Thr Ala35 40 45gtc aca gct ggt ggt tcc ctc ctt gtt ctc tcc agc ctt acc ctt gtt 1749Val Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu Thr Leu Val50 55 60 65gga act gtc ata gct ttg act gtt gca aca cct ctg ctc gtt atc ttc 1797Gly Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile Phe70 75 80agc cca atc ctt gtc ccg gct ctc atc aca gtt gca ctc ctc atc acc 1845Ser Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu Leu Ile Thr85 90 95ggt ttt ctt tcc tct gga ggg ttt ggc att gcc gct ata acc gtt ttc 1893Gly Phe Leu Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Val Phe100 105 110tct tgg att tac aa gtaagcacac atttatcatc ttacttcata attttgtgca1947Ser Trp Ile Tyr Lys115atatgtgcat gcatgtgttg agccagtagc tttggatcaa tttttttggt cgaataacaa 2007atgtaacaat aagaaattgc aaattctagg gaacatttgg ttaactaaat acgaaatttg 2067acctagctag cttgaatgtg tctgtgtata tcatctatat aggtaaaatg cttggtatga 2127tacctattga ttgtgaatag g tac gca acg gga gag cac cca cag gga tca 2178Tyr Ala Thr Gly Glu His Pro Gln Gly Ser
120 125gac aag ttg gac agt gca agg atg aag ttg gga agc aaa gct cag gat 2226Asp Lys Leu Asp Ser Ala Arg Met Lys Leu Gly Ser Lys Ala Gln Asp130 135 140ctg aaa gac aga gct cag tac tac gga cag caa cat act ggt ggg gaa 2274Leu Lys Asp Arg Ala Gln Tyr Tyr Gly Gln Gln His Thr Gly Gly Glu145 150 155 160cat gac cgt gac cgt act cgt ggt ggc cag cac act acc atg gct tcg 2322His Asp Arg Asp Arg Thr Arg Gly Gly Gln His Thr Thr Met Ala Ser165 170 175gaa gaa gga caa gtg atc gcc tgc cac acc gtt gag aca tgg aac gag 2370Glu Glu Gly Gln Val Ile Ala Cys His Thr Val Glu Thr Trp Asn Glu180 185 190cag ctt cag aag gct aat gaa tcc aaa act ctt gtg gtg gtt gat ttc 2418Gln Leu Gln Lys Ala Asn Glu Ser Lys Thr Leu Val Val Val Asp Phe195 200 205acg gct tct tgg tgt gga cca tgt cgt ttc atc gct cca ttc ttt gct 2466Thr Ala Ser Trp Cys Gly Pro Cys Arg Phe Ile Ala Pro Phe Phe Ala210 215 220gat ttg gct aag aaa ctt cct aac gtg ctt ttc ctc aag gtt gat act 2514Asp Leu Ala Lys Lys Leu Pro Asn Val Leu Phe Leu Lys Val Asp Thr225 230 235 240gat gaa ttg aag tcg gtg gca agt gat tgg gcg ata cag gcg atg cca 2562Asp Glu Leu Lys Ser Val Ala Ser Asp Trp Ala Ile Gln Ala Met Pro245 250 255acc ttc atg ttt ttg aag gaa ggg aag att ttg gac aaa gtt gtt gga 2610Thr Phe Met Phe Leu Lys Glu Gly Lys Ile Leu Asp Lys Val Val Gly260 265 270gcc aag aaa gat gag ctt cag tct acc att gcc aaa cac ttg gct taa 2658Ala Lys Lys Asp Glu Leu Gln Ser Thr Ile Ala Lys His Leu Ala *275 280 285g cttaataagt atgaactaaa atgcatgtag gtgtaagagc tcatggagag 2709catggaatat tgtatccgac catgtaacag tataataact gagctccatc tcacttcttc 2769tatgaataaa caaaggatgt tatgatatat taacactcta tctatgcacc ttattgttct 2829atgataaatt tcctcttatt attataaatc atctgaatcg tgacggctta tggaatgctt 2889caaatagtac aaaaacaaat gtgtactata agactttcta aacaattcta actttagcat 2949tgtgaacgag acataagtgt taagaagaca taacaattat aatggaagaa gtttgtctcc 3009atttatatat tatatattac ccacttatgt attatattag gatgttaagg agacataaca 3069attataaaga gagaagtttg tatccattta tatattatat actacccatt tatatattat 3129acttatccac ttatttaatg tctttataag gtttgatcca tgatatttct aatattttag 3189ttgatatgta tatgaaaggg tactatttga actctcttac tctgtataaa ggttggatca 3249tccttaaagt gggtctattt aattttattg cttcttacag ataaaaaaaa aattatgagt 3309tggtttgata aaatattgaa ggatttaaaa taataataaa taataaataa catataatat 3369atgtatataa atttattata atataacatt tatctataaa aaagtaaata ttgtcataaa 3429tctatacaat cgtttagcct tgctggacga ctctcaatta tttaaacgag agtaaacata 3489tttgactttt tggttattta acaaattatt atttaacact atatgaaatt tttttttttt 3549atcggcaagg aaataaaatt aaattaggag ggacaatggt gtgtcccaat ccttatacaa 3609ccaacttcca caggaaggtc aggtcgggga caacaaaaaa acaggcaagg gaaatttttt 3669aatttgggtt gtcttgtttg ctgcataatt tatgcagtaa aacactacac ataacccttt 3729tagcagtaga gcaatggttg accgtgtgct tagcttcttt tattttattt ttttatcagc 3789aaagaataaa taaaataaaa tgagacactt cagggatgtt tcaaccctta tacaaaaccc 3849caaaaacaag tttcctagca ccctaccaac taaggtacc388821017211118212PRT213人工序列40017Met Ala Asp Thr Ala Arg Gly Thr His His Asp Ile Ile Gly Arg Asp1 5 10 15Gln Tyr Pro Met Met Gly Arg Asp Arg Asp Gln Tyr Gln Met Ser Gly20 25 30Arg Gly Ser Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala Ala Thr35 40 45Ala Val Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu Thr Leu50 55 60Val Gly Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile65 70 75 80Phe Ser Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu Leu Ile85 90 95Thr Gly Phe Leu Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Val100 105 110Phe Ser Trp Ile Tyr Lys11521018211169212PRT213人工序列40018Tyr Ala Thr Gly Glu His Pro Gln Gly Ser Asp Lys Leu Asp Ser Ala1 5 10 15Arg Met Lys Leu Gly Ser Lys Ala Gln Asp Leu Lys Asp Arg Ala Gln20 25 30Tyr Tyr Gly Gln Gln His Thr Gly Gly Glu His Asp Arg Asp Arg Thr35 40 45Arg Gly Gly Gln His Thr Thr Met Ala Ser Glu Glu Gly Gln Val Ile50 55 60Ala Cys His Thr Val Glu Thr Trp Asn Glu Gln Leu Gln Lys Ala Asn65 70 75 80Glu Ser Lys Thr Leu Val Val Val Asp Phe Thr Ala Ser Trp Cys Gly85 90 95Pro Cys Arg Phe Ile Ala Pro Phe Phe Ala Asp Leu Ala Lys Lys Leu100 105 110Pro Asn Val Leu Phe Leu Lys Val Asp Thr Asp Glu Leu Lys Ser Val115 120 125Ala Ser Asp Trp Ala Ile Gln Ala Met Pro Thr Phe Met Phe Leu Lys130 135 140Glu Gly Lys Ile Leu Asp Lys Val Val Gly Ala Lys Lys Asp Glu Leu145 150 155 160Gln Ser Thr Ile Ala Lys His Leu Ala165210192113888212DNA213人工序列220223嵌合221CDS222(1555)...(2249)221CDS222(2490)...(2658)40019ctgcaggaat tcattgtact cccagtatca ttatagtgaa agttttggct ctctcgccgg 60tggtttttta cctctattta aaggggtttt ccacctaaaa attctggtat cattctcact 120ttacttgtta ctttaatttc tcataatctt tggttgaaat tatcacgctt ccgcacacga 180tatccctaca aatttattat ttgttaaaca ttttcaaacc gcataaaatt ttatgaagtc 240ccgtctatct ttaatgtagt ctaacatttt catattgaaa tatataattt acttaatttt 300agcgttggta gaaagcataa tgatttattc ttattcttct tcatataaat gtttaatata 360caatataaac aaattcttta ccttaagaag gatttcccat tttatatttt aaaaatatat 420ttatcaaata tttttcaacc acgtaaatct cataataata agttgtttca aaagtaataa 480aatttaactc cataattttt ttattcgact gatcttaaag caacacccag tgacacaact 540agccattttt ttctttgaat aaaaaaatcc aattatcatt gtattttttt tatacaatga 600aaatttcacc aaacaatcat ttgtggtatt tctgaagcaa gtcatgttat gcaaaattct 660ataattccca tttgacacta cggaagtaac tgaagatctg cttttacatg cgagacacat 720cttctaaagt aattttaata atagttacta tattcaagat ttcatatatc aaatactcaa 780tattacttct aaaaaattaa ttagatataa ttaaaatatt acttttttaa ttttaagttt 840aattgttgaa tttgtgacta ttgatttatt attctactat gtttaaattg ttttatagat 900agtttaaagt aaatataagt aatgtagtag agtgttagag tgttacccta aaccataaac 960tataagattt atggtggact aattttcata tatttcttat tgcttttacc ttttcttggt 1020atgtaagtcc gtaactggaa ttactgtggg ttgccatggc actctgtggt cttttggttc 1080atgcatggat gcttgcgcaa gaaaaagaca aagaacaaag aaaaaagaca aaacagagag 1140acaaaacgca atcacacaac caactcaaat tagtcactgg ctgatcaaga tcgccgcgtc 1200catgtatgtc taaatgccat gcaaagcaac acgtgcttaa catgcacttt aaatggctca 1260cccatctcaa cccacacaca aacacattgc ctttttcttc atcatcacca caaccacctg 1320tatatattca ttctcttccg ccacctcaat ttcttcactt caacacacgt caacctgcat 1380atgcgtgtca tcccatgccc aaatctccat gcatgttcca accaccttct ctcttatata 1440atacctataa atacctctaa tatcactcac ttctttcatc atccatccat ccagagtact 1500actactctac tactataata ccccaaccca actcatattc aatactactc tact atg 1557Met1gct tcg gaa gaa gga caa gtg atc gcc tgc cac acc gtt gag aca tgg 1605Ala Ser Glu Glu Gly Gln Val Ile Ala Cys His Thr Val Glu Thr Trp5 10 15aac gag cag ctt cag aag gct aat gaa tcc aaa act ctt gtg gtg gtt 1653Asn Glu Gln Leu Gln Lys Ala Asn Glu Ser Lys Thr Leu Val Val Val20 25 30gat ttc acg gct tct tgg tgt gga cca tgt cgt ttc atc gct cca ttc 1701Asp Phe Thr Ala Ser Trp Cys Gly Pro Cys Arg Phe Ile Ala Pro Phe35 40 45ttt gct gat ttg gct aag aaa ctt cct aac gtg ctt ttc ctc aag gtt 1749Phe Ala Asp Leu Ala Lys Lys Leu Pro Asn Val Leu Phe Leu Lys Val50 55 60 65gat act gat gaa ttg aag tcg gtg gca agt gat tgg gcg ata cag gcg 1797Asp Thr Asp Glu Leu Lys Ser Val Ala Ser Asp Trp Ala Ile Gln Ala70 75 80atg cca acc ttc atg ttt ttg aag gaa ggg aag att ttg gac aaa gtt 1845Met Pro Thr Phe Met Phe Leu Lys Glu Gly Lys Ile Leu Asp Lys Val85 90 95gtt gga gcc aag aaa gat gag ctt cag tct acc att gcc aaa cac ttg 1893Val Gly Ala Lys Lys Asp Glu Leu Gln Ser Thr Ile Ala Lys His Leu100 105 110gct atg gcg gat aca gct aga gga acc cat cac gat atc atc ggc aga 1941Ala Met Ala Asp Thr Ala Arg Gly Thr His His Asp Ile Ile Gly Arg115 120 125gac cag tac ccg atg atg ggc cga gac cga gac cag tac cag atg tcc 1989Asp Gln Tyr Pro Met Met Gly Arg Asp Arg Asp Gln Tyr Gln Met Ser130 135 140 145gga cga gga tct gac tac tcc aag tct agg cag att gct aaa gct gca 2037Gly Arg Gly Ser Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala Ala150 155 160act gct gtc aca gct ggt ggt tcc ctc ctt gtt ctc tcc agc ctt acc 2085Thr Ala Val Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu Thr165 170 175ctt gtt gga act gtc ata gct ttg act gtt gca aca cct ctg ctc gtt 2133Leu Val Gly Thr Val Ile Ala Leu Thr ValAla T hr Pro Leu Leu Val180 185 190atc ttc agc cca atc ctt gtc ccg gct ctc atc aca gtt gca ctc ctc 2181Ile Phe Ser Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu Leu195 200 205atc acc ggt ttt ctt tcc tct gga ggg ttt ggc att gcc gct ata acc 2229Ile Thr Gly Phe Leu Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr210 215 220 225gtt ttc tct tgg att tac aa gtaagcacac atttatcatc ttacttcata 2279Val Phe Ser Trp Ile Tyr Lys230attttgtgca atatgtgcat gcatgtgttg agccagtagc tttggatcaa tttttttggt 2339cgaataacaa atgtaacaat aagaaattgc aaattctagg gaacatttgg ttaactaaat 2399acgaaatttg acctagctag cttgaatgtg tctgtgtata tcatctatat aggtaaaatg 2459cttggtatga tacctattga ttgtgaatag g tac gca acg gga gag cac cca2511Tyr Ala Thr Gly Glu His Pro235cag gga tca gac aag ttg gac agt gca agg atg aag ttg gga agc aaa 2559Gln Gly Ser Asp Lys Leu Asp Ser Ala Arg Met Lys Leu Gly Ser Lys240 245 250 255gct cag gat ctg aaa gac aga gct cag tac tac gga cag caa cat act 2607Ala Gln Asp Leu Lys Asp Arg Ala Gln Tyr Tyr Gly Gln Gln His Thr260 265 270ggt ggg gaa cat gac cgt gac cgt act cgt ggt ggc cag cac act act 2655Gly Gly Glu His Asp Arg Asp Arg Thr Arg Gly Gly Gln His Thr Thr275 280 285taa gcttaataag tatgaactaa aatgcatgta ggtgtaagag ctcatggaga2708*gcatggaata ttgtatccga ccatgtaaca gtataataac tgagctccat ctcacttctt 2768ctatgaataa acaaaggatg ttatgatata ttaacactct atctatgcac cttattgttc 2828tatgataaat ttcctcttat tattataaat catctgaatc gtgacggctt atggaatgct 2888tcaaatagta caaaaacaaa tgtgtactat aagactttct aaacaattct aactttagca 2948ttgtgaacga gacataagtg ttaagaagac ataacaatta taatggaaga agtttgtctc 3008catttatata ttatatatta cccacttatg tattatatta ggatgttaag gagacataac 3068aattataaag agagaagttt gtatccattt atatattata tactacccat ttatatatta 3128tacttatcca cttatttaat gtctttataa ggtttgatcc atgatatttc taatatttta 3188gttgatatgt atatgaaagg gtactatttg aactctctta ctctgtataa aggttggatc 3248atccttaaag tgggtctatt taattttatt gcttcttaca gataaaaaaa aaattatgag 3308ttggtttgat aaaatattga aggatttaaa ataataataa ataataaata acatataata 3368tatgtatata aatttattat aatataacat ttatctataa aaaagtaaat attgtcataa 3428atctatacaa tcgtttagcc ttgctggacg actctcaatt atttaaacga gagtaaacat 3488atttgacttt ttggttattt aacaaattat tatttaacac tatatgaaat tttttttttt 3548tatcggcaag gaaataaaat taaattagga gggacaatgg tgtgtcccaa tccttataca 3608accaacttcc acaggaaggt caggtcgggg acaacaaaaa aacaggcaag ggaaattttt 3668taatttgggt tgtcttgttt gctgcataat ttatgcagta aaacactaca cataaccctt 3728ttagcagtag agcaatggtt gaccgtgtgc ttagcttctt ttattttatt tttttatcag 3788caaagaataa ataaaataaa atgagacact tcagggatgt ttcaaccctt atacaaaacc 3848ccaaaaacaa gtttcctagc accctaccaa ctaaggtacc 388821020211232212PRT213人工序列220223嵌合40020Met Ala Ser Glu Glu Gly Gln Val Ile Ala Cys His Thr Val Glu Thr1 5 10 15Trp Asn Glu Gln Leu Gln Lys Ala Asn Glu Ser Lys Thr Leu Val Val20 25 30Val Asp Phe Thr Ala Ser Trp Cys Gly Pro Cys Arg Phe Ile Ala Pro35 40 45Phe Phe Ala Asp Leu Ala Lys Lys Leu Pro Asn Val Leu Phe Leu Lys50 55 60Val Asp Thr Asp Glu Leu Lys Ser Val Ala Ser Asp Trp Ala lle Gln65 70 75 80Ala Met Pro Thr Phe Met Phe Leu Lys Glu Gly Lys Ile Leu Asp Lys85 90 95Val Val Gly Ala Lys Lys Asp Glu Leu Gln Ser Thr Ile Ala Lys His100 105 110Leu Ala Met Ala Asp Thr Ala Arg Gly Thr His His Asp Ile Ile Gly115 120 125Arg Asp Gln Tyr Pro Met Met Gly Arg Asp Arg Asp Gln Tyr Gln Met130 135 140Ser Gly Arg Gly Ser Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala145 150 155 160Ala Thr Ala Val Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu165 170 175Thr Leu Val Gly Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu180 185 190Val Ile Phe Ser Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu195 200 205Leu Ile Thr Gly Phe Leu Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile210 215 220Thr Val Phe Ser Trp Ile Tyr Lys225 2302102121155212PRT213人工序列220223嵌合40021Tyr Ala Thr Gly Glu His Pro Gln Gly Ser Asp Lys Leu Asp Ser Ala15 10 15Arg Met Lys Leu Gly Ser Lys Ala Gln Asp Leu Lys Asp Arg Ala Gln20 25 30Tyr Tyr Gly Gln Gln His Thr Gly Gly Glu His Asp Arg Asp Arg Thr35 40 45Arg Gly Gly Gln His Thr Thr50 55210222113787212DNA213人工序列220223嵌合221CDS222(1555)...(2556)40022ctgcaggaat tcattgtact cccagtatca ttatagtgaa agttttggct ctctcgccgg 60tggtttttta cctctattta aaggggtttt ccacctaaaa attctggtat cattctcact 120ttacttgtta ctttaatttc tcataatctt tggttgaaat tatcacgctt ccgcacacga 180tatccctaca aatttattat ttgttaaaca ttttcaaacc gcataaaatt ttatgaagtc 240ccgtctatct ttaatgtagt ctaacatttt catattgaaa tatataattt acttaatttt 300agcgttggta gaaagcataa tgatttattc ttattcttct tcatataaat gtttaatata 360caatataaac aaattcttta ccttaagaag gatttcccat tttatatttt aaaaatatat 420ttatcaaata tttttcaacc acgtaaatct cataataata agttgtttca aaagtaataa 480aatttaactc cataattttt ttattcgact gatcttaaag caacacccag tgacacaact 540agccattttt ttctttgaat aaaaaaatcc aattatcatt gtattttttt tatacaatga 600aaatttcacc aaacaatcat ttgtggtatt tctgaagcaa gtcatgttat gcaaaattct 660ataattccca tttgacacta cggaagtaac tgaagatctg cttttacatg cgagacacat 720cttctaaagt aattttaata atagttacta tattcaagat ttcatatatc aaatactcaa 780tattacttct aaaaaattaa ttagatataa ttaaaatatt acttttttaa ttttaagttt 840aattgttgaa tttgtgacta ttgatttatt attctactat gtttaaattg ttttatagat 900agtttaaagt aaatataagt aatgtagtag agtgttagag tgttacccta aaccataaac 960tataagattt atggtggact aattttcata tatttcttat tgcttttacc ttttcttggt 1020atgtaagtcc gtaactggaa ttactgtggg ttgccatggc actctgtggt cttttggttc 1080atgcatggat gcttgcgcaa gaaaaagaca aagaacaaag aaaaaagaca aaacagagag 1140acaaaacgca atcacacaac caactcaaat tagtcactgg ctgatcaaga tcgccgcgtc 1200catgtatgtc taaatgccat gcaaagcaac acgtgcttaa catgcacttt aaatggctca 1260cccatctcaa cccacacaca aacacattgc ctttttcttc atcatcacca caaccacctg 1320tatatattca ttctcttccg ccacctcaat ttcttcactt caacacacgt caacctgcat 1380atgcgtgtca tcccatgccc aaatctccat gcatgttcca accaccttct ctcttatata 1440atacctataa atacctctaa tatcactcac ttctttcatc atccatccat ccagagtact 1500actactctac tactataata ccccaaccca actcatattc aatactactc tact atg 1557Met1aat ggt ctc gaa act cac aac aca agg ctc tgt atc gta gga agt ggc 1605Asn Gly Leu Glu Thr His Asn Thr Arg Leu Cys Ile Val Gly Ser Gly5 10 15cca gcg gca cac acg gcg gcg att tac gca gct agg gct gaa ctt aaa 1653Pro Ala Ala His Thr Ala Ala Ile Tyr Ala Ala Arg Ala Glu Leu Lys20 25 30cct ctt ctc ttc gaa gga tgg atg gct aac gac atc gct ccc ggt ggt 1701Pro Leu Leu Phe Glu Gly Trp Met Ala Asn Asp Ile Ala Pro Gly Gly35 40 45caa cta aca acc acc acc gac gtc gag aat ttc ccc gga ttt cca gaa 1749Gln Leu Thr Thr Thr Thr Asp Val Glu Asn Phe Pro Gly Phe Pro Glu50 55 60 65ggt att ctc gga gta gag ctc act gac aaa ttc cgt aaa caa tcg gag 1797Gly Ile Leu Gly Val Glu Leu Thr Asp Lys Phe Arg Lys Gln Ser Glu70 75 80cga ttc ggt act acg ata ttt aca gag acg gtg acg aaa gtc gat ttc 1845Arg Phe Gly Thr Thr Ile Phe Thr Glu Thr Val Thr Lys Val Asp Phe85 90 95tct tcg aaa ccg ttt aag cta ttc aca gat tca aaa gcc att ctc gct 1893Ser Ser Lys Pro Phe Lys Leu Phe Thr Asp Ser Lys Ala Ile Leu Ala100 105 110gac gct gtg att ctc gct act gga gct gtg gct aag cgg ctt agc ttc 1941Asp Ala Val Ile Leu Ala Thr Gly Ala Val Ala Lys Arg Leu Ser Phe115 120 125gtt gga tct ggt gaa ggt tct gga ggt ttc tgg aac cgt gga atc tcc 1989Val Gly Ser Gly Glu Gly Ser Gly Gly Phe Trp Asn Arg Gly Ile Ser130 135 140 145gct tgt gct gtt tgc gac gga gct gct ccg ata ttc cgt aac aaa cct 2037Ala Cys Ala Val Cys Asp Gly Ala Ala Pro Ile Phe Arg Ash Lys Pro150 155 160ctt gcg gtg atc ggt gga ggc gat tca gca atg gaa gaa gca aac ttt 2085Leu Ala Val Ile Gly Gly Gly Asp Ser Ala Met Glu Glu Ala Asn Phe165 170 175ctt aca aaa tat gga tct aaa gtg tat ata atc cat agg aga gat gct 2133Leu Thr Lys Tyr Gly Ser Lys Val Tyr Ile Ile His Arg Arg Asp Ala180 185 190ttt aga gcg tct aag att atg cag cag cga gct ttg tct aat cct aag 2181Phe Arg Ala Ser Lys Ile Met Gln Gln Arg Ala Leu Ser Asn Pro Lys195 200 205att gat gtg att tgg aac tcg tct gtt gtg gaa gct tat gga gat gga 2229Ile Asp Val Ile Trp Asn Ser Ser Val Val Glu Ala Tyr Gly Asp Gly210 215 220 225gaa aga gat gtg ctt gga gga ttg aaa gtg aag aat gtg gtt acc gga 2277Glu Arg Asp Val Leu Gly Gly Leu Lys Val Lys Asn Val Val Thr Gly230 235 240gat gtt tct gat tta aaa gtt tct gga ttg ttc ttt gct att ggt cat 2325Asp Val Ser Asp Leu Lys Val Ser Gly Leu Phe Phe Ala Ile Gly His245 250 255gag cca gct acc aag ttt ttg gat ggt ggt gtt gag tta gat tcg gat 2373Glu Pro Ala Thr Lys Phe Leu Asp Gly Gly Val Glu Leu Asp Ser Asp260 265 270ggt tat gtt gtc acg aag cct ggt act aca cag act agc gtt ccc gga 2421Gly Tyr Val Val Thr Lys Pro Gly Thr Thr Gln Thr Ser Val Pro Gly275 280 285gtt ttc gct gcg ggt gat gtt cag gat aag aag tat agg caa gcc atc 2469Val Phe Ala Ala Gly Asp Val Gln Asp Lys Lys Tyr Arg Gln Ala Ile290 295 300 305act gct gca gga act ggg tgc atg gca gct ttg gat gca gag cat tac 2517Thr Ala Ala Gly Thr Gly Cys Met Ala Ala Leu Asp Ala Glu His Tyr310 315 320tta caa gag att gga tct cag caa ggt aag agt gat tga agcttaataa2566Leu Gln Glu Ile Gly Ser Gln Gln Gly Lys Ser Asp *325 330gtatgaacta aaatgcatgt aggtgtaaga gctcatggag agcatggaat attgtatccg 2626accatgtaac agtataataa ctgagctcca tctcacttct tctatgaata aacaaaggat 2686gttatgatat attaacactc tatctatgca ccttattgtt ctatgataaa tttcctctta 2746ttattataaa tcatctgaat cgtgacggct tatggaatgc ttcaaatagt acaaaaacaa 2806atgtgtacta taagactttc taaacaattc taactttagc attgtgaacg agacataagt 2866gttaagaaga cataacaatt ataatggaag aagtttgtct ccatttatat attatatatt 2926acccacttat gtattatatt aggatgttaa ggagacataa caattataaa gagagaagtt 2986tgtatccatt tatatattat atactaccca tttatatatt atacttatcc acttatttaa 3046tgtctttata aggtttgatc catgatattt ctaatatttt agttgatatg tatatgaaag 3106ggtactattt gaactctctt actctgtata aaggttggat catccttaaa gtgggtctat 3166ttaattttat tgcttcttac agataaaaaa aaaattatga gttggtttga taaaatattg 3226aaggatttaa aataataata aataataaat aacatataat atatgtatat aaatttatta 3286taatataaca tttatctata aaaaagtaaa tattgtcata aatctataca atcgtttagc 3346cttgctggac gactctcaat tatttaaacg agagtaaaca tatttgactt tttggttatt 3406taacaaatta ttatttaaca ctatatgaaa tttttttttt ttatcggcaa ggaaataaaa 3466ttaaattagg agggacaatg gtgtgtccca atccttatac aaccaacttc cacaggaagg 3526tcaggtcggg gacaacaaaa aaacaggcaa gggaaatttt ttaatttggg ttgtcttgtt 3586tgctgcataa tttatgcagt aaaacactac acataaccct tttagcagta gagcaatggt 3646tgaccgtgtg cttagcttct tttattttat ttttttatca gcaaagaata aataaaataa 3706aatgagacac ttcagggatg tttcaaccct tatacaaaac cccaaaaaca agtttcctag 3766caccctacca actaaggtac c 378721023211333212PRT213人工序列220223嵌合40023Met Asn Gly Leu Glu Thr His Asn Thr Arg Leu Cys Ile Val Gly Ser1 5 10 15Gly Pro Ala Ala His Thr Ala Ala Ile Tyr Ala Ala Arg Ala Glu Leu20 25 30Lys Pro Leu Leu Phe Glu Gly Trp Met Ala Asn Asp Ile Ala Pro Gly35 40 45Gly Gln Leu Thr Thr Thr Thr Asp Val Glu Asn Phe Pro Gly Phe Pro50 55 60Glu Gly Ile Leu Gly Val Glu Leu Thr Asp Lys Phe Arg Lys Gln Ser65 70 75 80Glu Arg Phe Gly Thr Thr Ile Phe Thr Glu Thr Val Thr Lys Val Asp85 90 95Phe Ser Ser Lys Pro Phe Lys Leu Phe Thr Asp Ser Lys Ala Ile Leu100 105 110Ala Asp Ala Val Ile Leu Ala Thr Gly Ala Val Ala Lys Arg Leu Ser115 120 125Phe Val Gly Ser Gly Glu Gly Ser Gly Gly Phe Trp Asn Arg Gly Ile130 135 140Ser Ala Cys Ala Val Cys Asp Gly Ala Ala Pro Ile Phe Arg Asn Lys145 150 155 160Pro Leu Ala Val Ile Gly Gly Gly Asp Ser Ala Met Glu Glu Ala Asn165 170 175Phe Leu Thr Lys Tyr Gly Ser Lys Val Tyr Ile Ile His Arg Arg Asp180 185 190Ala Phe Arg Ala Ser Lys Ile Met Gln Gln Arg Ala Leu Ser Asn Pro195 200 205Lys Ile Asp Val Ile Trp Asn Ser Ser Val Val Glu Ala Tyr Gly Asp210 215 220Gly Glu Arg Asp Val Leu Gly Gly Leu Lys Val Lys Asn Val Val Thr225 230 235 240Gly Asp Val Ser Asp Leu Lys Val Ser Gly Leu Phe Phe Ala Ile Gly245 250 255His Glu Pro Ala Thr Lys Phe Leu Asp Gly Gly Val Glu Leu Asp Ser260 265 270Asp Gly Tyr Val Val Thr Lys Pro Gly Thr Thr Gln Thr Ser Val Pro275 280 285Gly Val Phe Ala Ala Gly Asp Val Gln Asp Lys Lys Tyr Arg Gln Ala290 295 300Ile Thr Ala Ala Gly Thr Gly Cys Met Ala Ala Leu Asp Ala Glu His305 310 315 320Tyr Leu Gln Glu Ile Gly Ser Gln Gln Gly Lys Ser Asp325 330210242114546212DNA213人工序列220221CDS222(1555)...(1907)221CDS222(2148)...(3315)223嵌合40024ctgcaggaat tcattgtact cccagtatca ttatagtgaa agttttggct ctctcgccgg 60tggtttttta cctctattta aaggggtttt ccacctaaaa attctggtat cattctcact 120ttacttgtta ctttaatttc tcataatctt tggttgaaat tatcacgctt ccgcacacga 180tatccctaca aatttattat ttgttasaca ttttcaaacc gcataaaatt ttatgaagtc 240ccgtctatct ttaatgtagt ctaacatttt catattgaaa tatataattt acttaatttt 300agcgttggta gaaagcataa tgatttattc ttattcttct tcatataaat gtttaatata 360caatataaac aaattcttta ccttaagaag gatttcccat tttatatttt aaaaatatat 420ttatcaaata tttttcaacc acgtaaatct cataataata agttgtttca aaagtaataa 480aatttaactc cataattttt ttattcgact gatcttaaag caacacccag tgacacaact 540agccattttt ttctttgaat aaaaaaatcc aattatcatt gtattttttt tatacaatga 600aaatttcacc aaacaatcat ttgtggtatt tctgaagcaa gtcatgttat gcaaaattct 660ataattccca tttgacacta cggaagtaac tgaagatctg cttttacatg cgagacacat 720cttctaaagt aattttaata atagttacta tattcaagat ttcatatatc aaatactcaa 780tattacttct aaaaaattaa ttagatataa ttaaaatatt acttttttaa ttttaagttt 840aattgttgaa tttgtgacta ttgatttatt attctactat gtttaaattg ttttatagat 900agtttaaagt aaatataagt aatgtagtag agtgttagag tgttacccta aaccataaac 960tataagattt atggtggact aattttcata tatttcttat tgcttttacc ttttcttggt 1020atgtaagtcc gtaactggaa ttactgtggg ttgccatggc actctgtggt cttttggttc 1080atgcatggat gcttgcgcaa gaaaaagaca aagaacaaag aaaaaagaca aaacagagag 1140acaaaacgca atcacacaac caactcaaat tagtcactgg ctgatcaaga tcgccgcgtc 1200catgtatgtc taaatgccat gcaaagcaac acgtgcttaa catgcacttt aaatggctca 1260cccatctcaa cccacacaca aacacattgc ctttttcttc atcatcacca caaccacctg 1320tatatattca ttctcttccg ccacctcaat ttcttcactt caacacacgt caacctgcat 1380atgcgtgtca tcccatgccc aaatctccat gcatgttcca accaccttct ctcttatata 1440atacctataa atacctctaa tatcactcac ttctttcatc atccatccat ccagagtact 1500actactctac tactataata ccccaaccca actcatattc aatactactc tact atg 1557Met1gcg gat aca gct aga gga acc cat cac gat atc atc ggc aga gac cag 1605Ala Asp Thr Ala Arg Gly Thr His His Asp Ile Ile Gly Arg Asp Gln5 10 15tac ccg atg atg ggc cga gac cga gac cag tac cag atg tcc gga cga 1653Tyr Pro Met Met Gly Arg Asp Arg Asp Gln Tyr Gln Met Ser Gly Arg20 25 30gga tct gac tac tcc aag tct agg cag att gct aaa gct gca act gct 1701Gly Ser Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala Ala Thr Ala35 40 45gtc aca gct ggt ggt tcc ctc ctt gtt ctc tcc agc ctt acc ctt gtt 1749Val Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu Thr Leu Val50 55 60 65gga act gtc ata gct ttg act gtt gca aca cct ctg ctc gtt atc ttc 1797Gly Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile Phe70 75 80agc cca atc ctt gtc ccg gct ctc atc aca gtt gca ctc ctc atc acc 1845Ser Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu Leu Ile Thr85 90 95ggt ttt ctt tcc tct gga ggg ttt ggc att gcc gct ata acc gtt ttc 1893Gly Phe Leu Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Val Phe100 105 110tct tgg att tac aa gtaagcacac atttatcatc ttacttcata attttgtgca1947Ser Trp Ile Tyr Lys115atatgtgcat gcatgtgttg agccagtagc tttggatcaa tttttttggt cgaataacaa 2007atgtaacaat aagaaattgc aaattctagg gaacatttgg ttaactaaat acgaaatttg 2067acctagctag cttgaatgtg tctgtgtata tcatctatat aggtaaaatg cttggtatga 2127tacctattga ttgtgaatag g tac gca acg gga gag cac cca cag gga tca 2178Tyr Ala Thr Gly Glu His Pro Gln Gly Ser120 125gac aag ttg gac agt gca agg atg aag ttg gga agc aaa gct cag gat 2226Asp Lys Leu Asp Ser Ala Arg Met Lys Leu Gly Ser Lys Ala Gln Asp130 135 140ctg aaa gac aga gct cag tac tac gga cag caa cat act ggt ggg gaa 2274Leu Lys Asp Arg Ala Gln Tyr Tyr Gly Gln Gln His Thr Gly Gly Glu145 150 155 160cat gac cgt gac cgt act cgt ggt ggc cag cac act acc atg aat ggt 2322His Asp Arg Asp Arg Thr Arg Gly Gly Gln His Thr Thr Met Asn Gly165 170 175ctc gaa act cac aac aca agg ctc tgt atc gta gga agt ggc cca gcg 2370Leu Glu Thr His Asn Thr Arg Leu Cys Ile Val Gly Ser Gly Pro Ala180 185 190gca cac acg gcg gcg att tac gca gct agg gct gaa ctt aaa cct ctt 2418Ala His Thr Ala Ala Ile Tyr Ala Ala Arg Ala Glu Leu Lys Pro Leu195 200 205ctc ttc gaa gga tgg atg gct aac gac atc gct ccc ggt ggt caa cta 2466Leu Phe Glu Gly Trp Met Ala Asn Asp Ile Ala Pro Gly Gly Gln Leu210 215 220aca acc acc acc gac gtc gag aat ttc ccc gga ttt cca gaa ggt att 2514Thr Thr Thr Thr Asp Val Glu Asn Phe Pro Gly Phe Pro Glu Gly Ile225 230 235 240ctc gga gta gag ctc act gac aaa ttc cgt aaa caa tcg gag cga ttc 2562Leu Gly Val Glu Leu Thr Asp Lys Phe Arg Lys Gln Ser Glu Arg Phe245 250 255ggt act acg ata ttt aca gag acg gtg acg aaa gtc gat ttc tct tcg 2610Gly Thr Thr Ile Phe Thr Glu Thr Val Thr Lys Val Asp Phe Ser Ser260 265 270aaa ccg ttt aag cta ttc aca gat tca aaa gcc att ctc gct gac gct 2658Lys Pro Phe Lys Leu Phe Thr Asp Ser Lys Ala Ile Leu Ala Asp Ala275 280 285gtg att ctc gct act gga gct gtg gct aag cgg ctt agc ttc gtt gga 2706Val Ile Leu Ala Thr Gly Ala Val Ala Lys Arg Leu Ser Phe Val Gly290 295 300tct ggt gaa ggt tct gga ggt ttc tgg aac cgt gga atc tcc gct tgt 2754Ser Gly Glu Gly Ser Gly Gly Phe Trp Asn Arg Gly Ile Ser Ala Cys305 310 315 320gct gtt tgc gac gga gct gct ccg ata ttc cgt aac aaa cct ctt gcg 2802Ala Val Cys Asp Gly Ala Ala Pro Ile Phe Arg Asn Lys Pro Leu Ala325 330 335gtg atc ggt gga ggc gat tca gca atg gaa gaa gca aac ttt ctt aca 2850Val Ile Gly Gly Gly Asp Ser Ala Met Glu Glu Ala Asn Phe Leu Thr340 345 350aaa tat gga tct aaa gtg tat ata atc cat agg aga gat gct ttt aga 2898Lys Tyr Gly Ser Lys Val Tyr Ile Ile His Arg Arg Asp Ala Phe Arg355 360 365gcg tct aag att atg cag cag cga gct ttg tct aat cct aag att gat 2946Ala Ser Lys Ile Met Gln Gln Arg Ala Leu Ser Asn Pro Lys Ile Asp370 375 380gtg att tgg aac tcg tct gtt gtg gaa gct tat gga gat gga gaa aga 2994Val Ile Trp Asn Ser Ser Val Val Glu Ala Tyr Gly Asp Gly Glu Arg385 390 395 400gat gtg ctt gga gga ttg aaa gtg aag aat gtg gtt acc gga gat gtt 3042Asp Val Leu Gly Gly Leu Lys Val Lys Asn Val Val Thr Gly Asp Val405 410 415tct gat tta aaa gtt tct gga ttg ttc ttt gct att ggt cat gag cca 3090Ser Asp Leu Lys Val Ser Gly Leu Phe Phe Ala Ile Gly His Glu Pro420 425 430gct acc aag ttt ttg gat ggt ggt gtt gag tta gat tcg gat ggt tat 3138Ala Thr Lys Phe Leu Asp Gly Gly Val Glu Leu Asp Ser Asp Gly Tyr435 440 445gtt gtc acg aag cct ggt act aca cag act agc gtt ccc gga gtt ttc 3186Val Val Thr Lys Pro Gly Thr Thr Gln Thr Ser Val Pro Gly Val Phe450 455 460gct gcg ggt gat gtt cag gat aag aag tat agg caa gcc atc act gct 3234Ala Ala Gly Asp Val Gln Asp Lys Lys Tyr Arg Gln Ala Ile Thr Ala465 470 475 480gca gga act ggg tgc atg gca gct ttg gat gca gag cat tac tta caa 3282Ala Gly Thr Gly Cys Met Ala Ala Leu Asp Ala Glu His Tyr Leu Gln485 490 495gag att gga tct cag caa ggt aag agt gat tga agcttaataa gtatgaacta 3335Glu Ile Gly Ser Gln Gln Gly Lys Ser Asp *500 505aaatgcatgt aggtgtaaga gctcatggag agcatggaat attgtatccg accatgtaac 3395agtataataa ctgagctcca tctcacttct tctatgaata aacaaaggat gttatgatat 3455attaacactc tatctatgca ccttattgtt ctatgataaa tttcctctta ttattataaa 3515tcatctgaat cgtgacggct tatggaatgc ttcaaatagt acaaaaacaa atgtgtacta 3575taagactttc taaacaattc taactttagc attgtgaacg agacataagt gttaagaaga 3635cataacaatt ataatggaag aagtttgtct ccatttatat attatatatt acccacttat 3695gtattatatt aggatgttaa ggagacataa caattataaa gagagaagtt tgtatccatt 3755tatatattat atactaccca tttatatatt atacttatcc acttatttaa tgtctttata 3815aggtttgatc catgatattt ctaatatttt agttgatatg tatatgaaag ggtactattt 3875gaactctctt actctgtata aaggttggat catccttaaa gtgggtctat ttaattttat 3935tgcttcttac agataaaaaa aaaattatga gttggtttga taaaatattg aaggatttaa 3995aataataata aataataaat aacatataat atatgtatat aaatttatta taatataaca 4055tttatctata aaaaagtaaa tattgtcata aatctataca atcgtttagc cttgctggac 4115gactctcaat tatttaaacg agagtaaaca tatttgactt tttggttatt taacaaatta 4175ttatttaaca ctatatgaaa tttttttttt ttatcggcaa ggaaataaaa ttaaattagg 4235agggacaatg gtgtgtccca atccttatac aaccaacttc cacaggsagg tcaggtcggg 4295gacaacaaaa aaacaggcaa gggaaatttt ttaatttggg ttgtcttgtt tgctgcataa 4355tttatgcagt aaaacactac acataaccct tttagcagta gagcaatggt tgaccgtgtg 4415cttagcttct tttattttat ttttttatca gcaaagaata aataaaataa aatgagacac 4475ttcagggatg tttcaaccct tatacaaaac cccaaaaaca agtttcctag caccctacca 4535actaaggtac c 454621025211118212PRT213人工序列220223嵌合40025Met Ala Asp Thr Ala Arg Gly Thr His His Asp Ile Ile Gly Arg Asp1 5 10 15Gln Tyr Pro Met Met Gly Arg Asp Arp Asp Gln Tyr Gln Met Ser Gly20 25 30Arg Gly Ser Asp Tyr Ser Lys Ser Arg Gln lle Ala Lys Ala Ala Thr35 40 45Ala Val Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu Thr Leu50 55 60Val Gly Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile65 70 75 80Phe Ser Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu Leu Ile85 90 95Thr Gly Phe Leu Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Val100 105 110Phe Ser Trp Ile Tyr Lys11521026211388212PRT213人工序列220223嵌合40026Tyr Ala Thr Gly Glu His Pro Gln Gly Ser Asp Lys Leu Asp Ser Ala1 5 10 15Arg Met Lys Leu Gly Ser Lys Ala Gln Asp Leu Lys Asp Arg Ala Gln20 25 30Tyr Tyr Gly Gln Gln His Thr Gly Gly Glu His Asp Arg Asp Arg Thr35 40 45Arg Gly Gly Gln His Thr Thr Met Asn Gly Leu Glu Thr His Asn Thr50 55 60Arg Leu Cys Ile Val Gly Ser Gly Pro Ala Ala His Thr Ala Ala Ile65 70 75 80Tyr Ala Ala Arg Ala Glu Leu Lys Pro Leu Leu Phe Glu Gly Trp Met85 90 95Ala Asn Asp Ile Ala Pro Gly Gly Gln Leu Thr Thr Thr Thr Asp Val100 105 110Glu Asn Phe Pro Gly Phe Pro Glu Gly Ile Leu Gly Val Glu Leu Thr115 120 125Asp Lys Phe Arg Lys Gln Ser Glu Arg Phe Gly Thr Thr Ile Phe Thr130 135 140Glu Thr Val Thr Lys Val Asp Phe Ser Ser Lys Pro Phe Lys Leu Phe145 150 155 160Thr Asp Ser Lys Ala Ile Leu Ala Asp Ala Val Ile Leu Ala Thr Gly165 170 175Ala Val Ala Lys Arg Leu Ser Phe Val Gly Ser Gly Glu Gly Ser Gly180 185 190Gly Phe Trp Asn Arg Gly Ile Ser Ala Cys Ala Val Cys Asp Gly Ala195 200 205Ala Pro Ile Phe Arg Ash Lys Pro Leu Ala Val Ile Gly Gly Gly Asp210 215 220Ser Ala Met Glu Glu Ala Asn Phe Leu Thr Lys Tyr Gly Ser Lys Val225 230 235 240Tyr Ile Ile His Arg Arg Asp Ala Phe Arg Ala Ser Lys Ile Met Gln245 250 255Gln Arg Ala Leu Ser Asn Pro Lys Ile Asp Val Ile Trp Asn Ser Ser260 265 270Val Val Glu Ala Tyr Gly Asp Gly Glu Arg Asp Val Leu Gly Gly Leu275 280 285Lys Val Lys Asn Val Val Thr Gly Asp Val Ser Asp Leu Lys Val Ser290 295 300Gly Leu Phe Phe Ala Ile Gly His Glu Pro Ala Thr Lys Phe Leu Asp305 310 315 320Gly Gly Val Glu Leu Asp Ser Asp Gly Tyr Val Val Thr Lys Pro Gly
325 330 335Thr Thr Gln Thr Ser Val Pro Gly Val Phe Ala Ala Gly Asp Val Gln340 345 350Asp Lys Lys Tyr Arg Gln Ala Ile Thr Ala Ala Gly Thr Gly Cys Met355 360 365Ala Ala Leu Asp Ala Glu His Tyr Leu Gln Glu Ile Gly Ser Gln Gln370 375 380Gly Lys Ser Asp385210272114545212DNA213人工序列220223嵌合221CDS222(1555)...(2906)221CDS222(3147)...(3315)40027ctgcaggaat tcattgtact cccagtatca ttatagtgaa agttttggct ctctcgccgg 60tggtttttta cctctattta aaggggtttt ccacctaaaa attctggtat cattctcact 120ttacttgtta ctttaatttc tcataatctt tggttgaaat tatcacgctt ccgcacacga 180tatccctaca aatttattat ttgttaaaca ttttcaaacc gcataaaatt ttatgaagtc 240ccgtctatct ttaatgtagt ctaacatttt catattgaaa tatataattt acttaatttt 300agcgttggta gaaagcataa tgatttattc ttattcttct tcatataaat gtttaatata 360caatataaac aaattcttta ccttaagaag gatttcccat tttatatttt aaaaatatat 420ttatcaaata tttttcaacc acgtaaatct cataataata agttgtttca aaagtaataa 480aatttaactc cataattttt ttattcgact gatcttaaag caacacccag tgacacaact 540agccattttt ttctttgaat aaaaaaatcc aattatcatt gtattttttt tatacaatga 600aaatttcacc aaacaatcat ttgtggtatt tctgaagcaa gtcatgttat gcaaaattct 660ataattccca tttgacacta cggaagtaac tgaagatctg cttttacatg cgagacacat 720cttctaaagt aattttaata atagttacta tattcaagat ttcatatatc aaatactcaa 780tattacttct aaaaaattaa ttagatataa ttaaaatatt acttttttaa ttttaagttt 840aattgttgaa tttgtgacta ttgatttatt attctactat gtttaaattg ttttatagat 900agtttaaagt aaatataagt aatgtagtag agtgttagag tgttacccta aaccataaac 960tataagattt atggtggact aattttcata tatttcttat tgcttttacc ttttcttggt 1020atgtaagtcc gtaactggaa ttactgtggg ttgccatggc actctgtggt cttttggttc 1080atgcatggat gcttgcgcaa gaaaaagaca aagaacaaag aaaaaagaca aaacagagag 1140acaaaacgca atcacacaac caactcaaat tagtcactgg ctgatcaaga tcgccgcgtc 1200catgtatgtc taaatgccat gcaaagcaac acgtgcttaa catgcacttt aaatggctca 1260cccatctcaa cccacacaca aacacattgc ctttttcttc atcatcacca caaccacctg 1320tatatattca ttctcttccg ccacctcaat ttcttcactt caacacacgt caacctgcat 1380atgcgtgtca tcccatgccc aaatctccat gcatgttcca accaccttct ctcttatata 1440atacctataa atacctctaa tatcactcac ttctttcatc atccatccat ccagagtact 1500actactctac tactataata ccccaaccca actcatattc aatactactc tact atg 1557Met1aat ggt ctc gaa act cac aac aca agg ctc tgt atc gta gga agt ggc 1605Asn Gly Leu Glu Thr His Asn Thr Arg Leu Cys Ile Val Gly Ser Gly5 10 15cca gcg gca cac acg gcg gcg att tac gca gct agg gct gaa ctt aaa 1653Pro Ala Ala His Thr Ala Ala Ile Tyr Ala Ala Arg Ala Glu Leu Lys20 25 30cct ctt ctc ttc gaa gga tgg atg gct aac gac atc gct ccc ggt ggt 1701Pro Leu Leu Phe Glu Gly Trp Met Ala Asn Asp Ile Ala Pro Gly Gly35 40 45caa cta aca acc acc acc gac gtc gag aat ttc ccc gga ttt cca gaa 1749Gln Leu Thr Thr Thr Thr Asp Val Glu Asn Phe Pro Gly Phe Pro Glu50 55 60 65ggt att ctc gga gta gag ctc act gac aaa ttc cgt aaa caa tcg gag 1797Gly Ile Leu Gly Val Glu Leu Thr Asp Lys Phe Arg Lys Gln Ser Glu70 75 80cga ttc ggt act acg ata ttt aca gag acg gtg acg aaa gtc gat ttc 1845Arg Phe Gly Thr Thr Ile Phe Thr Glu Thr Val Thr Lys Val Asp Phe85 90 95tct tcg aaa ccg ttt aag cta ttc aca gat tca aaa gcc att ctc gct 1893Ser Ser Lys Pro Phe Lys Leu Phe Thr Asp Ser Lys Ala Ile Leu Ala100 105 110gac gct gtg att ctc gct act gga gct gtg gct aag cgg ctt agc ttc 1941Asp Ala Val Ile Leu Ala Thr Gly Ala Val Ala Lys Arg Leu Ser Phe115 120 125gtt gga tct ggt gaa ggt tct gga ggt ttc tgg aac cgt gga atc tcc 1989Val Gly Ser Gly Glu Gly Ser Gly Gly Phe Trp Asn Arg Gly Ile Ser130 135 140 145gct tgt gct gtt tgc gac gga gct gct ccg ata ttc cgt aac aaa cct 2037Ala Cys Ala Val Cys Asp Gly Ala Ala Pro Ile Phe Arg Asn Lys Pro150 155 160ctt gcg gtg atc ggt gga ggc gat tca gca atg gaa gaa gca aac ttt 2085Leu Ala Val Ile Gly Gly Gly Asp Ser Ala Met Glu Glu Ala Asn Phe165 170 175ctt aca aaa tat gga tct aaa gtg tat ata atc cat agg aga gat gct 2133Leu Thr Lys Tyr Gly Ser Lys Val Tyr Ile Ile His Arg Arg Asp Ala180 185 190ttt aga gcg tct aag att atg cag cag cga gct ttg tct aat cct aag 2181Phe Arg Ala Ser Lys Ile Met Gln Gln Arg Ala Leu Set Asn Pro Lys195 200 205att gat gtg att tgg aac tcg tct gtt gtg gaa gct tat gga gat gga 2229Ile Asp Val Ile Trp Asn Set Ser Val Val Glu Ala Tyr Gly Asp Gly210 215 220 225gaa aga gat gtg ctt gga gga ttg aaa gtg aag aat gtg gtt acc gga 2277Glu Arg Asp Val Leu Gly Gly Leu Lys Val Lys Asn Val Val Thr Gly230 235 240gat gtt tct gat tta aaa gtt tct gga ttg ttc ttt gct att ggt cat 2325Asp Val Ser Asp Leu Lys Val Ser Gly Leu Phe Phe Ala Ile Gly His245 250 255gag cca gct acc aag ttt ttg gat ggt ggt gtt gag tta gat tcg gat 2373Glu Pro Ala Thr Lys Phe Leu Asp Gly Gly Val Glu Leu Asp Ser Asp260 265 270ggt tat gtt gtc acg aag cct ggt act aca cag act agc gtt ccc gga 2421Gly Tyr Val Val Thr Lys Pro Gly Thr Thr Gln Thr Ser Val Pro Gly275 280 285gtt ttc gct gcg ggt gat gtt cag gat aag aag tat agg caa gcc atc 2469Val Phe Ala Ala Gly Asp Val Gln Asp Lys Lys Tyr Arg Gln Ala Ile290 295 300 305act gct gca gga act ggg tgc atg gca gct ttg gat gca gag cat tac 2517Thr Ala Ala Gly Thr Gly Cys Met Ala Ala Leu Asp Ala Glu His Tyr310 315 320tta caa gag att gga tct cag caa ggt aag agt gat atg gcg gat aca 2565Leu Gln Glu Ile Gly Ser Gln Gln Gly Lys Ser Asp Met Ala Asp Thr325 330 335gct aga gga acc cat cac gat atc atc ggc aga gac cag tac ccg atg 2613Ala Arg Gly Thr His His Asp Ile Ile Gly Arg Asp Gln Tyr Pro Met340 345 350atg ggc cga gac cga gac cag tac cag atg tcc gga cga gga tct gac 2661Met Gly Arg Asp Arg Asp Gln Tyr Gln Met Ser Gly Arg Gly Ser Asp355 360 365tac tcc aag tct agg cag att gct aaa gct gca act gct gtc aca gct 2709Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala Ala Thr Ala Val Thr Ala370 375 380 385ggt ggt tcc ctc ctt gtt ctc tcc agc ctt acc ctt gtt gga act gtc 2757Gly Gly Ser Leu Leu Val Leu Ser Ser Leu Thr Leu Val Gly Thr Val390 395 400ata gct ttg act gtt gca aca cct ctg ctc gtt atc ttc agc cca atc 2805Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile Phe Ser Pro Ile405410 415ctt gtc ccg gct ctc atc aca gtt gca ctc ctc atc acc ggt ttt ctt 2853Leu Val Pro Ala Leu Ile Thr Val Ala Leu Leu Ile Thr Gly Phe Leu420 425 430tcc tct gga ggg ttt ggc att gcc gct ata acc gtt ttc tct tgg att 2901Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Val Phe Ser Trp Ile435 440 445tac aa gtaagcacac atttatcatc ttacttcata attttgtgca atatgtgcat 2956Tyr Lys450gcatgtgttg agccagtagc tttggatcaa tttttttggt cgaataacaa atgtaacaat 3016aagaaattgc aaattctagg gaacatttgg ttaactaaat acgaaatttg acctagctag 3076cttgaatgtg tctgtgtata tcatctatat aggtaaaatg cttggtatga tacctattga 3136ttgtgaatag g tac gca acg gga gag cac cca cag gga tca gac aag ttg 3186Tyr Ala Thr Gly Glu His Pro Gln Gly Ser Asp Lys Leu455 460gac agt gca agg atg aag ttg gga agc aaa gct cag gat ctg aaa gac 3234Asp Ser Ala Arg Met Lys Leu Gly Ser Lys Ala Gln Asp Leu Lys Asp465 470 475 480aga gct cag tac tac gga cag caa cat act ggt ggg gaa cat gac cgt 3282Arg Ala Gln Tyr Tyr Gly Gln Gln His Thr Gly Gly Glu His Asp Arg485 490 495gac cgt act cgt ggt ggc cag cac act act taa gcttaataag tatgaactaa 3335Asp Arg Thr Arg Gly Gly Gln His Thr Thr *500 505aatgcatgta ggtgtaagag ctcatggaga gcatggaata ttgtatccga ccatgtaaca 3395gtataataac tgagctccat ctcacttctt ctatgaataa acaaaggatg ttatgatata 3455ttaacactct atctatgcac cttattgttc tatgataaat ttcctcttat tattataaat 3515catctgaatc gtgacggctt atggaatgct tcaaatagta caaaaacaaa tgtgtactat 3575aagactttct aaacaattct aactttagca ttgtgaacga gacataagtg ttaagaagac 3635ataacaatta taatggaaga agtttgtctc catttatata ttatatatta cccacttatg 3695tattatatta ggatgttaag gagacataac aattataaag agagaagttt gtatccattt 3755atatattata tactacccat ttatatatta tacttatcca cttatttaat gtctttataa 3815ggtttgatcc atgatatttc taatatttta gttgatatgt atatgaaagg gtactatttg 3875aactctctta ctctgtataa aggttggatc atccttaaag tgggtctatt taattttatt 3935gcttcttaca gataaaaaaa aaattatgag ttggtttgat aaaatattga aggatttaaa 3995ataataataa ataataaata acatataata tatgtatata aatttattat aatataacat 4055ttatctataa aaaagtaaat attgtcataa atctatacaa tcgtttagcc ttgctggacg 4115actctcaatt atttaaacga gagtaaacat atttgacttt ttggttattt aacsaattat 4175tatttaacac tatatgaaat tttttttttt tatcggcaag gaaataaaat taaattagga 4235gggacaatgg tgtgtcccaa tccttataca accaacttcc acaggaaggt caggtcgggg 4295acaacaaaaa aacaggcaag ggaaattttt taatttgggt tgtcttgttt gctgcataat 4355ttatgcagta aaacactaca cataaccctt ttagcagtag agcaatggtt gaccgtgtgc 4415ttagcttctt ttattttatt tttttatcag caaagaataa ataaaataaa atgagacact 4475tcagggatgt ttcaaccctt atacaaaacc ccaaaaacaa gtttcctagc accctaccaa 4535ctaaggtacc454521028211451212PRT213人工序列220223嵌合40028Met Asn Gly Leu Glu Thr His Asn Thr Arg Leu Cys Ile Val Gly Ser1 5 10 15Gly Pro Ala Ala His Thr Ala Ala Ile Tyr Ala Ala Arg Ala Glu Leu20 25 30Lys Pro Leu Leu Phe Glu Gly Trp Met Ala Asn Asp Ile Ala Pro Gly35 40 45Gly Gln Leu Thr Thr Thr Thr Asp Val Glu Asn Phe Pro Gly Phe Pro50 55 60Glu Gly Ile Leu Gly Val Glu Leu Thr Asp Lys Phe Arg Lys Gln Ser65 70 75 80Glu Arg Phe Gly Thr Thr Ile Phe Thr Glu Thr Val Thr Lys Val Asp85 90 95Phe Ser Ser Lys Pro Phe Lys Leu Phe Thr Asp Ser Lys Ala Ile Leu100 105 110Ala Asp Ala Val Ile Leu Ala Thr Gly Ala Val Ala Lys Arg Leu Ser115 120 125Phe Val Gly Ser Gly Glu Gly Ser Gly Gly Phe Trp Asn Arg Gly Ile130 135 140Ser Ala Cys Ala Val Cys Asp Gly Ala Ala Pro Ile Phe Arg Asn Lys145 150 155 160Pro Leu Ala Val Ile Gly Gly Gly Asp Ser Ala Met Glu Glu Ala Asn165 170 175Phe Leu Thr Lys Tyr Gly Ser Lys Val Tyr Ile Ile His Arg Arg Asp180 185 190Ala Phe Arg Ala Ser Lys Ile Met Gln Gln Arg Ala Leu Ser Asn Pro195 200 205Lys Ile Asp Val Ile Trp Asn Ser Ser Val Val Glu Ala Tyr Gly Asp210 215 220Gly Glu Arg Asp Val Leu Gly Gly Leu Lys Val Lys Asn Val Val Thr225 230 235 240Gly Asp Val Ser Asp Leu Lys Val Ser Gly Leu Phe Phe Ala Ile Gly245 250 255His Glu Pro Ala Thr Lys Phe Leu Asp Gly Gly Val Glu Leu Asp Ser260 265 270Asp Gly Tyr Val Val Thr Lys Pro Gly Thr Thr Gln Thr Ser Val Pro275 280 285Gly Val Phe Ala Ala Gly Asp Val Gln Asp Lys Lys Tyr Arg Gln Ala290 295 300Ile Thr Ala Ala Gly Thr Gly Cys Met Ala Ala Leu Asp Ala Glu His305 310 315 320Tyr Leu Gln Glu Ile Gly Ser Gln Gln Gly Lys Ser Asp Met Ala Asp325 330 335Thr Ala Arg Gly Thr His His Asp Ile Ile Gly Arg Asp Gln Tyr Pro340 345 350Met Met Gly Arg Asp Arg Asp Gln Tyr Gln Met Ser Gly Arg Gly Ser355 360 365Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala Ala Thr Ala Val Thr
370 375 380Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu Thr Leu Val Gly Thr385 390 395 400Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile Phe Ser Pro405 410 415Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu Leu Ile Thr Gly Phe420 425 430Leu Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Val Phe Ser Trp435 440 445Ile Tyr Lys4502102921155212PRT213人工序列220223嵌合40029Tyr Ala Thr Gly Glu His Pro Gln Gly Ser Asp Lys Leu Asp Ser Ala1 5 10 15Arg Met Lys Leu Gly Ser Lys Ala Gln Asp Leu Lys Asp Arg Ala Gln20 25 30Tyr Tyr Gly Gln Gln His Thr Gly Gly Glu His Asp Arg Asp Arg Thr35 40 45Arg Gly Gly Gln His Thr Thr50 55210302114922212DNA213人工序列220221CDS222(1555)...(1907)221CDS222(2148)...(3690)223嵌合40030ctgcaggaat tcattgtact cccagtatca ttatagtgaa agttttggct ctctcgccgg 60tggtttttta cctctattta aaggggtttt ccacctaaaa attctggtat cattctcact 120ttacttgtta ctttaatttc tcataatctt tggttgaaat tatcacgctt ccgcacacga 180tatccctaca aatttattat ttgttaaaca ttttcaaacc gcataaaatt ttatgaagtc 240ccgtctatct ttaatgtagt ctaacatttt catattgaaa tatataattt acttaatttt 300agcgttggta gaaagcataa tgatttattc ttattcttct tcatataaat gtttaatata 360caatataaac aaattcttta ccttaagaag gatttcccat tttatatttt aaaaatatat 420ttatcaaata tttttcaacc acgtaaatct cataataata agttgtttca aaagtaataa 480aatttaactc cataattttt ttattcgact gatcttaaag caacacccag tgacacaact 540agccattttt ttctttgaat aaaaaaatcc aattatcatt gtattttttt tatacaatga 600aaatttcacc aaacaatcat ttgtggtatt tctgaagcaa gtcatgttat gcaaaattct 660ataattccca tttgacacta cggaagtaac tgaagatctg cttttacatg cgagacacat 720cttctaaagt aattttaata atagttacta tattcaagat ttcatatatc aaatactcaa 780tattacttct aaaaaattaa ttagatataa ttaaaatatt acttttttaa ttttaagttt 840aattgttgaa tttgtgacta ttgatttatt attctactat gtttaaattg ttttatagat 900agtttaaagt aaatataagt aatgtagtag agtgttagag tgttacccta aaccataaac 960tataagattt atggtggact aattttcata tatttcttat tgcttttacc ttttcttggt 1020atgtaagtcc gtaactggaa ttactgtgggttgccatggc actctgtggt cttttggttc 1080atgcatggat gcttgcgcaa gaaaaagaca aagaacaaag aaaaaagaca aaacagagag 1140acaaaacgca atcacacaac caactcaaat tagtcactgg ctgatcaaga tcgccgcgtc 1200catgtatgtc taaatgccat gcaaagcaac acgtgcttaa catgcacttt aaatggctca 1260cccatctcaa cccacacaca aacacattgc ctttttcttc atcatcacca caaccacctg 1320tatatattca ttctcttccg ccacctcaat ttcttcactt caacacacgt caacctgcat 1380atgcgtgtca tcccatgccc aaatctccat gcatgttcca accaccttct ctcttatata 1440atacctataa atacctctaa tatcactcac ttctttcatc atccatccat ccagagtact 1500actactctac tactataata ccccaaccca actcatattc aatactactc tact atg 1557Met1gcg gat aca gct aga gga acc cat cac gat atc atc ggc aga gac cag 1605Ala Asp Thr Ala Arg Gly Thr His His Asp Ile Ile Gly Arg Asp Gln5 10 15tac ccg atg atg ggc cga gac cga gac cag tac cag atg tcc gga cga 1653Tyr Pro Met Met Gly Arg Asp Arg Asp Gln Tyr Gln Met Ser Gly Arg20 25 30gga tct gac tac tcc aag tct agg cag att gct aaa gct gca act gct 1701Gly Ser Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala Ala Thr Ala35 40 45gtc aca gct ggt ggt tcc ctc ctt gtt ctc tcc agc ctt acc ctt gtt 1749Val Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu Thr Leu Val50 55 60 65gga act gtc ata gct ttg act gtt gca aca cct ctg ctc gtt atc ttc 1797Gly Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile Phe70 75 80agc cca atc ctt gtc ccg gct ctc atc aca gtt gca ctc ctc atc acc 1845Ser Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu Leu Ile Thr85 90 95ggt ttt ctt tcc tct gga ggg ttt ggc att gcc gct ata acc gtt ttc 1893Gly Phe Leu Set Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Val Phe100 105 110tct tgg att tac aa gtaagcacac atttatcatc ttacttcata attttgtgca1947Ser Trp Ile Tyr Lys115atatgtgcat gcatgtgttg agccagtagc tttggatcaa tttttttggt cgaataacaa 2007atgtaacaat aagaaattgc aaattctagg gaacatttgg ttaactaaat acgaaatttg 2067acctagctag cttgaatgtg tctgtgtata tcatctatat aggtaaaatg cttggtatga 2127tacctattga ttgtgaatag g tac gca acg g ga gag cac cca cag gga tca 2178Tyr Ala Thr Gly Glu His Pro Gln Gly Ser120 125gac aag ttg gac agt gca agg atg aag ttg gga agc aaa gct cag gat 2226Asp Lys Leu Asp Ser Ala Arg Met Lys Leu Gly Ser Lys Ala Gln Asp130 135 140ctg aaa gac aga gct cag tac tac gga cag caa cat act ggt ggg gaa 2274Leu Lys Asp Arg Ala Gln Tyr Tyr Gly Gln Gln His Thr Gly Gly Glu145 150 155 160cat gac cgt gac cgt act cgt ggt ggc cag cac act acc atg aac acc 2322His Asp Arg Asp Arg Thr Arg Gly Gly Gln His Thr Thr Met Asn Thr165 170 175act cct tct gcg cat gag acg ata cac gaa gtg atc gtt att ggc tcc 2370Thr Pro Ser Ala His Glu Thr Ile His Glu Val Ile Val Ile Gly Ser180 185 190ggt cca gca ggc tac act gct gcc ctg tac gcc gct cgt gca cag cta 2418Gly Pro Ala Gly Tyr Thr Ala Ala Leu Tyr Ala Ala Arg Ala Gln Leu195 200 205aca ccg ctg gta ttt gag ggt acc tca ttc ggc ggc gcg ctg atg acc 2466Thr Pro Leu Va1 Phe Glu Gly Thr Ser Phe Gly Gly Ala Leu Met Thr210 215 220acc acc gag gtg gaa aac tac cca ggt ttt cgc aac ggc ata acc ggc 2514Thr Thr Glu Val Glu Asn Tyr Pro Gly Phe Arg Asn Gly Ile Thr Gly225 230 235 240ccg gag ttg atg gac gat atg cgt gaa cag gca ctg cga ttc ggc gcg 2562Pro Glu Leu Met Asp Asp Met Arg Glu Gln Ala Leu Arg Phe Gly Ala245 250 255gaa ctg cgg acc gaa gac gtc gag tcg gta tca ttg cgt ggc ccg atc 2610Glu Leu Arg Thr Glu Asp Val Glu Ser Val Ser Leu Arg Gly Pro Ile260 265 270aaa tcg gtc gtc acc gct gaa gga cag act tat cag gcc cga gcc gtc 2658Lys Ser Val Val Thr Ala Glu Gly Gln Thr Tyr Gln Ala Arg Ala Val275 280 285atc ctc gcc atg ggt acc tcc gtg cgt tat cta cag atc ccc ggc gag 2706Ile Leu Ala Met Gly Thr Ser Val Arg Tyr Leu Gln Ile Pro Gly Glu290 295 300caa gaa ttg cta gga cgt ggc gtg agt gca tgc gcg acc tgc gac ggg 2754Gln Glu Leu Leu Gly Arg Gly Val Ser Ala Cys Ala Thr Cys Asp Gly305 310 315 320tcc ttt ttc cgc ggc caa gac att gcc gtc att ggc ggt gga gac tca 2802Ser Phe Phe Arg Gly Gln Asp Ile Ala Val Ile Gly Gly Gly Asp Ser325 330 335gcg atg gag gaa gcc ctc ttt ttg acc cgg ttc gcc cgc agc gtc acg 2850Ala Met Glu Glu Ala Leu Phe Leu Thr Arg Phe Ala Arg Ser Val Thr340 345 350ctc gtg cac cgc cgc gac gaa ttc cga gct tct aag atc atg ctc ggt 2898Leu Val His Arg Arg Asp Glu Phe Arg Ala Ser Lys Ile Met Leu Gly355 360 365cgc gcc cgt aac aat gac aag atc aaa ttc atc acc aac cac acc gtg 2946Arg Ala Arg Asn Asn Asp Lys Ile Lys Phe Ile Thr Asn His Thr Val370 375 380gtc gcg gtg aac ggg tat aca aca gtg acc gga ttg cgg ttg cgt aac 2994Val Ala Val Asn Gly Tyr Thr Thr Val Thr Gly Leu Arg Leu Arg Asn385 390 395 400acc aca acg gga gag gaa acc acg cta gta gtg acc ggg gtt ttt gtt 3042Thr Thr Thr Gly Glu Glu Thr Thr Leu Val Val Thr Gly Val Phe Val405 410 415gca att ggc cat gaa cca cgt tcc agc ctg gtg agc gat gtc gtc gac 3090Ala Ile Gly His Glu Pro Arg Ser Ser Leu Val Ser Asp Val Val Asp420 425 430ata gac ccg gat ggc tac gtc ctg gtg aaa gga cgt acg acg agt aca 3138Ile Asp Pro Asp Gly Tyr Val Leu Val Lys Gly Arg Thr Thr Ser Thr435 440 445tcg atg gac ggc gtt ttt gcg gcc ggc gac ctg gta gat cgc acc tac 3186Ser Met Asp Gly Val Phe Ala Ala Gly Asp Leu Val Asp Arg Thr Tyr450 455 460cgg cag gcg atc act gcc gca ggt agt ggc tgt gcc gcc gcc atc gac 3234Arg Gln Ala Ile Thr Ala Ala Gly Ser Gly Cys Ala Ala Ala Ile Asp465 470 475 480gcc gaa cgt tgg ttg gcg gag cat gcc ggg tca aaa gct aac gaa aca 3282Ala Glu Arg Trp Leu Ala Glu His Ala Gly Ser Lys Ala Asn Glu Thr485 490 495aca gag gaa act gga gac gtt gac agt acc gac aca acc gat tgg agc 3330Thr Glu Glu Thr Gly Asp Val Asp Ser Thr Asp Thr Thr Asp Trp Ser500 505 510act gcg atg act gac gcc aag aac gcc ggg gtc aca ata gaa gtg acc 3378Thr Ala Met Thr Asp Ala Lys Asn Ala Gly Val Thr Ile Glu Val Thr515 520 525gat gct tcc ttt ttc gca gac gtc tta tcc agt aat aag cct gtg tta 3426Asp Ala Ser Phe Phe Ala Asp Val Leu Ser Ser Asn Lys Pro Val Leu530 535 540gtt gat ttt tgg gca aca tgg tgt gga ccc tgc aag atg gta gcg ccg 3474Val Asp Phe Trp Ala Thr Trp Cys Gly Pro Cys Lys Met Val Ala Pro545 550 555 560gta ctc gaa gag atc gcg tcc gaa caa cga aac cag ctc act gtc gcc 3522Val Leu Glu Glu Ile Ala Ser Glu Gln Arg Asn Gln Leu Thr Val Ala565 570 575aag tta gat gta gac acc aac ccg gaa atg gca cgc gag ttc cag gtc 3570Lys Leu Asp Val Asp Thr Asn Pro Glu Met Ala Arg Glu Phe Gln Val580 585 590gtg tcg ata ccc aca atg att ctg ttc cag ggt ggc caa cca gta aaa 3618Val Ser Ile Pro Thr Met Ile Leu Phe Gln Gly Gly Gln Pro Val Lys595 600 605cgc atc gtt ggc gct aag ggc aaa gca gcg tta cta cgt gac ctt tcc 3666Arg Ile Val Gly Ala Lys Gly Lys Ala Ala Leu Leu Arg Asp Leu Ser610 615 620gac gtg gta cct aac ctc aat taa gctttaaata agtatgaact aaaatgcatg 3720Asp Val Val Pro Asn Leu Asn *625 630taggtgtaag agctcatgga gagcatggaa tattgtatcc gaccatgtaa cagtataata 3780actgagctcc atctcacttc ttctatgaat aaacaaagga tgttatgata tattaacact 3840ctatctatgc accttattgt tctatgataa atttcctctt attattataa atcatctgaa 3900tcgtgacggc ttatggaatg cttcaaatag tacaaaaaca aatgtgtact ataagacttt 3960ctaaacaatt ctaactttag cattgtgaac gagacataag tgttaagaag acataacaat 4020tataatggaa gaagtttgtc tccatttata tattatatat tacccactta tgtattatat 4080taggatgtta aggagacata acaattataa agagagaagt ttgtatccat ttatatatta 4140tatactaccc atttatatat tatacttatc cacttattta atgtctttat aaggtttgat 4200ccatgatatt tctaatattt tagttgatat gtatatgaaa gggtactatt tgaactctct 4260tactctgtat aaaggttgga tcatccttaa agtgggtcta tttaatttta ttgcttctta 4320cagataaaaa aaaaattatg agttggtttg ataaaatatt gaaggattta aaataataat 4380aaataataaa taacatataa tatatgtata taaatttatt ataatataac atttatctat 4440aaaaaagtaa atattgtcat aaatctatac aatcgtttag ccttgctgga cgactctcaa 4500ttatttaaac gagagtaaac atatttgact ttttggttat ttaacaaatt attatttaac 4560actatatgaa attttttttt tttatcggca aggaaataaa attaaattag gagggacaat 4620ggtgtgtccc aatccttata caaccaactt ccacaggaag gtcaggtcgg ggacaacaaa 4680aaaacaggca agggaaattt tttaatttgg gttgtcttgt ttgctgcata atttatgcag 4740taaaacacta cacataaccc ttttagcagt agagcaatgg ttgaccgtgt gcttagcttc 4800ttttatttta tttttttatc agcaaagaat aaataaaata aaatgagaca cttcagggat 4860gtttcaaccc ttatacaaaa ccccaaaaac aagtttccta gcaccctacc aactaaggta 4920cc492221031211118212PRT213人工序列220223嵌合40031Met Ala Asp Thr Ala Arg Gly Thr His His Asp Ile Ile Gly Arg Asp1 5 10 15Gln Tyr Pro Met Met Gly Arg Asp Arg Asp Gln Tyr Gln Met Ser Gly20 25 30Arg Gly Ser Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala Ala Thr35 40 45Ala Val Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu Thr Leu50 55 60Val Gly Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile65 70 75 80Phe Ser Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu Leu Ile85 90 95Thr Gly Phe Leu Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Val100 105 110Phe Ser Trp Ile Tyr Lys11521032211513212PRT213人工序列220223嵌合40032Tyr Ala Thr Gly Glu His Pro Gln Gly Ser Asp Lys Leu Asp Ser Ala1 5 10 15Arg Met Lys Leu Gly Ser Lys Ala Gln Asp Leu Lys Asp Arg Ala Gln20 25 30Tyr Tyr Gly Gln Gln His Thr Gly Gly Glu His Asp Arg Asp Arg Thr35 40 45Arg Gly Gly Gln His Thr Thr Met Asn Thr Thr Pro Ser Ala His Glu50 55 60Thr Ile His Glu Val Ile Val Ile Gly Ser Gly Pro Ala Gly Tyr Thr65 70 75 80Ala Ala Leu Tyr Ala Ala Arg Ala Gln Leu Thr Pro Leu Val Phe Glu85 90 95Gly Thr Ser Phe Gly Gly Ala Leu Met Thr Thr Thr Glu Val Glu Asn100 105 110Tyr Pro Gly Phe Arg Asn Gly Ile Thr Gly Pro Glu Leu Met Asp Asp115 120 125Met Arg Glu Gln Ala Leu Arg Phe Gly Ala Glu Leu Arg Thr Glu Asp130 135 140Val Glu Ser Val Ser Leu Arg Gly Pro Ile Lys Ser Val Val Thr Ala145 150 155 160Glu Gly Gln Thr Tyr Gln Ala Arg Ala Val Ile Leu Ala Met Gly Thr165 170 175Ser Val Arg Tyr Leu Gln Ile Pro Gly Glu Gln Glu Leu Leu Gly Arg180 185 190Gly Val Ser Ala Cys Ala Thr Cys Asp Gly Ser Phe Phe Arg Gly Gln195 200 205Asp Ile Ala Val Ile Gly Gly Gly Asp Ser Ala Met Glu Glu Ala Leu210 215 220Phe Leu Thr Arg Phe Ala Arg Ser Val Thr Leu Val His Arg Arg Asp225 230 235 240Glu Phe Arg Ala Ser Lys Ile Met Leu Gly Arg Ala Arg Asn Asn Asp245 250 255Lys Ile Lys Phe Ile Thr Asn His Thr Val Val Ala Val Asn Gly Tyr260 265 270Thr Thr Val Thr Gly Leu Arg Leu Arg Asn Thr Thr Thr Gly Glu Glu275 280 285Thr Thr Leu Val Val Thr Gly Val Phe Val Ala Ile Gly His Glu Pro290 295 300Arg Ser Ser Leu Val Ser Asp Val Val Asp Ile Asp Pro Asp Gly Tyr305 310 315 320Val Leu Val Lys Gly Arg Thr Thr Ser Thr Ser Met Asp Gly Val Phe325 330 335Ala Ala Gly Asp Leu Val Asp Arg Thr Tyr Arg Gln Ala Ile Thr Ala340 345 350Ala Gly Ser Gly Cys Ala Ala Ala Ile Asp Ala Glu Arg Trp Leu Ala355 360 365Glu His Ala Gly Ser Lys Ala Asn Glu Thr Thr Glu Glu Thr Gly Asp370 375 380Val Asp Ser Thr Asp Thr Thr Asp Trp Ser Thr Ala Met Thr Asp Ala385 390 395 400Lys Asn Ala Gly Val Thr Ile Glu Val Thr Asp Ala Ser Phe Phe Ala405 410 415Asp Val Leu Ser Ser Asn Lys Pro Val Leu Val Asp Phe Trp Ala Thr420 425 430Trp Cys Gly Pro Cys Lys Met Val Ala Pro Val Leu Glu Glu Ile Ala435 440 445Ser Glu Gln Arg Asn Gln Leu Thr Val Ala Lys Leu Asp Val Asp Thr450 455 460Asn Pro Glu Met Ala Arg Glu Phe Gln Val Val Ser Ile Pro Thr Met465 470 475 480Ile Leu Phe Gln Gly Gly Gln Pro Val Lys Arg Ile Val Gly Ala Lys485 490 495Gly Lys Ala Ala Leu Leu Arg Asp Leu Ser Asp Val Val Pro Asn Leu500 505 510Asn210332114935212DNA213人工序列220221CDS222(1554)...(1906)221CDS222(2147)...(3701)223嵌合40033ctgcaggaat tcattgtact cccagtatca ttatagtgaa agttttggct ctctcgccgg 60tggtttttta cctctattta aaggggtttt ccacctaaaa attctggtat cattctcact 120ttacttgtta ctttaatttc tcataatctt tggttgaaat tatcacgctt ccgcacacga 180tatccctaca aatttattat ttgttaaaca ttttcaaacc gcataaaatt ttatgaagtc 240ccgtctatct ttaatgtagt ctaacatttt catattgaaa tatataattt acttaatttt 300agcgttggta gaaagcataa agatttattc ttattcttct tcatataaat gtttaatata 360caatataaac aaattcttta ccttaagaag gatttcccat tttatatttt aaaaatatat 420ttatcaaata tttttcaacc acgtaaatct cataataata agttgtttca aaagtaataa 480aatttaactc cataattttt ttattcgact gatcttaaag caacacccag tgacacaact 540agccattttt ttctttgaat aaaaaaatcc aattatcatt gtattttttt tatacaatga 600aaatttcacc aaacaatcat ttgtggtatt tctgaagcaa gtcatgttat gcaaaattct 660ataattccca tttgacacta cggaagtaac tgaagatctg cttttacatg cgagacacat 720cttctaaagt aattttaata atagttacta tattcaagat ttcatatatc aaatactcaa 780tattacttct aaaaaattaa ttagatataa ttaaaatatt acttttttaa ttttaagttt 840aattgttgaa tttgtgacta ttgatttatt attctactat gtttaaattg ttttatagat 900agtttaaagt aaatataagt aatgtagtag agtgttagag tgttacccta aaccataaac 960tataacattt atggtggact aattttcata tatttcttat tgcttttacc ttttcttggt 1020atgtaagtcc gtaactagaa ttacagtggg ttgccatggc actctgtggt cttttggttc 1080atgcatgggt cttgcgcaag aaaaagacaa agaacaaaga aaaaagacaa aacagagaga 1140caaaacgcaa tcacacaacc aactcaaatt agtcactggc tgatcaagat cgccgcgtcc 1200atgtatgtct aaatgccatg caaagcaaca cgtgcttaac atgcacttta aatggctcac 1260ccatctcaac ccacacacaa acacattgcc tttttcttca tcatcaccac aaccacctgt 1320atatattcat tctcttccgc cacctcaatt tcttcacttc aacacacgtc aacctgcata 1380tgcgtgtcat cccatgccca aatctccatg catgttccaa ccaccttctc tcttatataa 1440tacctataaa tacctctaat atcactcact tctttcatca tccatccatc cagagtacta 1500ctactctact actataatac cccaacccaa ctcatattca atactactct act atg1556Met1gcg gat aca gct aga gga acc cat cac gat atc atc ggc aga gac cag 1604Ala Asp Thr Ala Arg Gly Thr His His Asp Ile Ile Gly Arg Asp Gln5 10 15tac ccg atg atg ggc cga gac cga gac cag tac cag atg tcc gga cga 1652Tyr Pro Met Met Gly Arg Asp Arg Asp Gln Tyr Gln Met Ser Gly Arg20 25 30gga tct gac tac tcc aag tct agg cag att gct aaa gct gca act gct 1700Gly Ser Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala Ala Thr Ala35 40 45gtc aca gct ggt ggt tcc ctc ctt gtt ctc tcc agc ctt acc ctt gtt 1748Val Thr Ala Gly Gly Ser Leu Leu Val LEu Ser Ser Leu Thr Leu Val50 55 60 65gga act gtc ata gct ttg act gtt gca aca cct ctg ctc gtt atc ttc 1796Gly Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile Phe70 75 80agc cca atc ctt gtc ccg gct ctc atc aca gtt gca ctc ctc atc acc 1844Ser Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu Leu Ile Thr85 90 95ggt ttt ctt tcc tct gga ggg ttt ggc att gcc gct ata acc gtt ttc 1892Gly Phe Leu Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Val Phe100 105 110tct tgg att tac aa gtaagcacac atttatcatc ttacttcata attttgtgca1946Ser Trp Ile Tyr Lys115atatgtgcat gcatgtgttg agccagtagc tttggatcaa tttttttggt cgaataacaa 2006atgtaacaat aagaaattgc aaattctagg gaacatttgg ttaactaaat acgaaatttg 2066acctagctag cttgaatgtg tctgtgtata tcatctatat aggtaaaatg cttggtatga 2126tacctattga ttgtgaatag g tac gca acg gga gag cac cca cag gga tca 2177Tyr Ala Thr Gly Glu His Pro Gln Gly Ser120 125gac aag ttg gac agt gca agg atg aag ttg gga agc aaa gct cag gat 2225Asp Lys Leu Asp Ser Ala Arg Met Lys Leu Gly Ser Lys Ala Gln Asp130 135 140ctg aaa gac aga gct cag tac tac gga cag caa cat act ggt ggg gaa 2273Leu Lys Asp Arg Ala Gln Tyr Tyr Gly Gln Gln His Thr Gly Gly Glu145 150 155 160cat gac cgt gac cgt act cgt ggt ggc cag cac act acc atg aat ggt 2321His Asp Arg Asp Arg Thr Arg Gly Gly Gln His Tgr Thr Met Asn Gly165 170 175ctc gaa act cac aac aca agg ctc tgt atc gta gga agt ggc cca gcg 2369Leu Glu Thr His Asn Thr Arg Leu Cys Ile Val Gly Ser Gly Pro Ala180 185 190gca cac acg gcg gcg att tac gca gct agg gct gaa ctt aaa cct ctt 2417Ala His Thr Ala Ala Ile Tyr Ala Ala Arg Ala Glu Leu Lys Pro Leu195 200 205ctc ttc gaa gga tgg atg gct aac gac atc gct ccc ggt ggt caa cta 2465Leu Phe Glu Gly Trp Met Ala Asn Asp Ile Ala Pro Gly Gly Gln Leu210 215 220aca acc acc acc gac gtc gag aat ttc ccc gga ttt cca gaa ggt att 2513Thr Thr Thr Thr Asp Val Glu Asn Phe Pro Gly Phe Pro Glu Gly Ile225 230 235 240ctc gga gta gag ctc act gac aaa ttc cgt aaa caa tcg gag cga ttc 2561Leu Gly Val Glu Leu Thr Asp Lys Phe Arg Lys Gln Set Glu Arg Phe245 250 255ggt act acg ata ttt aca gag acg gtg acg aaa gtc gat ttc tct tcg 2609Gly Thr Thr Ile Phe Thr Glu Thr Val Thr Lys Val Asp Phe Ser Set260 265 270aaa ccg ttt aag cta ttc aca gat tca aaa gcc att ctc gct gac gct 2657Lys Pro Phe Lys Leu Phe Thr Asp Ser Lys Ala Ile Leu Ala Asp Ala275 280 285gtg att ctc gct act gga gct gtg gct aag cgg ctt agc ttc gtt gga 2705Val Ile Leu Ala Thr Gly Ala Val Ala Lys Arg Leu Ser Phe Val Gly290 295 300tct ggt gaa ggt tct gga ggt ttc tgg aac cgt gga atc tcc gct tgt 2753Ser Gly Glu Gly Ser Gly Gly Phe Trp Asn Arg Gly Ile Ser Ala Cys305 310 315 320gct gtt tgc gac gga gct gct ccg ata ttc cgt aac aaa cct ctt gcg 2801Ala Val Cys Asp Gly Ala Ala Pro Ile Phe Arg Asn Lys Pro Leu Ala325 330 335gtg atc ggt gga ggc gat tca gca atg gaa gaa gca aac ttt ctt aca 2849Val Ile Gly Gly Gly Asp Ser Ala Met Glu Glu Ala Asn Phe Leu Thr340 345 350aaa tat gga tct aaa gtg tat ata atc cat agg aga gat gct ttt aga 2897Lys Tyr Gly Ser Lys Val Tyr Ile Ile His Arg Arg Asp Ala Phe Arg355 360 365gcg tct aag att atg cag cag cga gct ttg tct aat cct aag att gat 2945Ala Ser Lys Ile Met Gln Gln Arg Ala Leu Ser Asn Pro Lys Ile Asp370 375 380gtg att tgg aac tcg tct gtt gtg gaa gct tat gga gat gga gaa aga 2993Val Ile Trp Asn Ser Ser Val Val Glu Ala Tyr Gly Asp Gly Glu Arg385 390 395 400gat gtg ctt gga gga ttg aaa gtg aag aat gtg gtt acc gga gat gtt 3041Asp Val Leu Gly Gly Leu Lys Val Lys Asn Val Val Thr Gly Asp Val405 410 415tct gat tta aaa gtt tct gga ttg ttc ttt gct att ggt cat gag cca 3089Ser Asp Leu Lys Val Ser Gly Leu Phe Phe Ala Ile Gly His Glu Pro420 425 430gct acc aag ttt ttg gat ggt ggt gtt gag tta gat tcg gat ggt tat 3137Ala Thr Lys Phe Leu Asp Gly Gly Val Glu Leu Asp Ser Asp Gly Tyr435 440 445gtt gtc acg aag cct ggt act aca cag act agc gtt ccc gga gtt ttc 3185Val Val Thr Lys Pro Gly Thr Thr Gln Thr Ser Val Pro Gly Val Phe450 455 460gct gcg ggt gat gtt cag gat aag aag tat agg caa gcc atc act gct 3233Ala Ala Gly Asp Val Gln Asp Lys Lys Tyr Arg Gln Ala Ile Thr Ala465 470 475 480gca gga act ggg tgc atg gca gct ttg gat gca gag cat tac tta caa 3281Ala Gly Thr Gly Cys Met Ala Ala Leu Asp Ala Glu His Tyr Leu Gln485 490 495gag att gct gga tcg aag gct aac gag acc acc gag gaa act gga gat 3329Glu Ile Ala Gly Ser Lys Ala Asn Glu Thr Thr Glu Glu Thr Gly Asp500 505 510gtt gac tcg acg gat act acg gat tgg tcg acg gct atg gaa gaa gga 3377Val Asp Ser Thr Asp Thr Thr Asp Trp Ser Thr Ala Met Glu Glu Gly515 520 525caa gtg atc gcc tgc cac acc gtt gag aca tgg aac gag cag ctt cag 3425Gln Val Ile Ala Cys His Thr Val Glu Thr Trp Asn Glu Gln Leu Gln530 535 540aag gct aat gaa tcc aaa act ctt gtg gtg gtt gat ttc acg gct tct 3473Lys Ala Asn Glu Ser Lys Thr Leu Val Val Val Asp Phe Thr Ala Ser545 550 555 560tgg tgt gga cca tgt cgt ttc atc gct cca ttc ttt gct gat ttg gct 3521Trp Cys Gly Pro Cys Arg Phe IleA la Pro Phe Phe Ala Asp Leu Ala565 570 575aag aaa ctt cct aac gtg ctt ttc ctc aag gtt gat act gat gaa ttg 3569Lys Lys Leu Pro Asn Val Leu Phe Leu Lys Val Asp Thr Asp Glu Leu580 585 590aag tcg gtg gca agt gat tgg gcg ata cag gcg atg cca acc ttc atg 3617Lys Ser Val Ala Ser Asp Trp Ala Ile Gln Ala Met Pro Thr Phe Met595 600 605ttt ttg aag gaa ggg aag att ttg gac aaa gtt gtt gga gcc aag aaa 3665Phe Leu Lys Glu Gly Lys Ile Leu Asp Lys Val Val Gly Ala Lys Lys610 615 620gat gag ctt cag tct acc att gcc aaa cac ttg gct taagcttaaa3711Asp Glu Leu Gln Ser Thr Ile Ala Lys His Leu Ala625 630 635taagtatgaa ctaaaatgca tgtaggtgta agagctcatg gagagcatgg aatattgtat 3771ccgaccatgt aacagtataa taactgagct ccatctcact tcttctatga ataaacaaag 3831gatgttatga tatattaaca ctctatctat gcaccttatt gttctatgat aaatttcctc 3891ttattattat aaatcatctg aatcgtgacg gcttatggaa tgcttcaaat agtacaaaaa 3951caaatgtgta ctataagact ttctaaacaa ttctaacttt agcattgtga acgagacata 4011agtgttaaga agacataaca attataatgg aagaagtttg tctccattta tatattatat 4071attacccact tatgtattat attaggatgt taaggagaca taacaattat aaagagagaa 4131gtttgtatcc atttatatat tatatactac ccatttatat attatactta tccacttatt 4191taatgtcttt ataaggtttg atccatgata tttctaatat tttagttgat atgtatatga 4251aagggtacta tttgaactct cttactctgt ataaaggttg gatcatcctt aaagtgggtc 4311tatttaattt tattgcttct tacagataaa aaaaaaatta tgagttggtt tgataaaata 4371ttgaaggatt taaaataata ataaataata aataacatat aatatatgta tataaattta 4431ttataatata acatttatct ataaaaaagt aaatattgtc ataaatctat acaatcgttt 4491agccttgctg gacgactctc aattatttaa acgagagtaa acatatttga ctttttggtt 4551atttaacaaa ttattattta acactatatg aaattttttt tttttatcgg caaggaaata 4611aaattaaatt aggagggaca atggtgtgtc ccaatcctta tacaaccaac ttccacagga 4671aggtcaggtc ggggacaaca aaaaaacagg caagggaaat tttttaattt gggttgtctt 4731gtttgctgca taatttatgc agtaaaacac tacacataac ccttttagca gtagagcaat 4791ggttgaccgt gtgcttagct tcttttattt tattttttta tcagcaaaga ataaataaaa 4851taaaatgaga cacttcaggg atgtttcaac ccttatacaa aaccccaaaa acaagtttcc 4911tagcacccta ccaactaagg tacc493521034211118212PRT213人工序列220221SITE222(1)...(118)223油質蛋白223嵌合40034Met Ala Asp Thr Ala Arg Gly Thr His His Asp Ile Ile Gly Arg Asp1 5 10 15Gln Tyr Pro Met Met Gly Arg Asp Arg Asp Gln Tyr Gln Met Ser Gly20 25 30Arg Gly Ser Asp Tyr Ser Lys Ser Arg Gln Ile Ala Lys Ala Ala Thr35 40 45Ala Val Thr Ala Gly Gly Ser Leu Leu Val Leu Ser Ser Leu Thr Leu50 55 60Val Gly Thr Val Ile Ala Leu Thr Val Ala Thr Pro Leu Leu Val Ile65 70 75 80Phe Ser Pro Ile Leu Val Pro Ala Leu Ile Thr Val Ala Leu Leu Ile85 90 95Thr Gly Phe Leu Ser Ser Gly Gly Phe Gly Ile Ala Ala Ile Thr Val100 105 110Phe Ser Trp Ile Tyr Lys11521035211518212PRT213人工序列220221SITE222(1)...(55)223油質蛋白221SITE222(56)...(383)223硫氧還蛋白還原酶221SITE222(384)...(406)223接頭221SITE222(407)...(518)223硫氧還蛋白223嵌合40035Tyr Ala Thr Gly Glu His Pro Gln Gly Ser Asp Lys Leu Asp Ser Ala1 5 10 15Arg Met Lys Leu Gly Ser Lys Ala Gln Asp Leu Lys Asp Arg Ala Gln20 25 30Tyr Tyr Gly Gln Gln His Thr Gly Gly Glu His Asp Arg Asp Arg Thr35 40 45Arg Gly Gly Gln His Thr Thr Met Asn Gly Leu Glu Thr His Asn Thr50 55 60Arg Leu Cys Ile Val Gly Ser Gly Pro Ala Ala His Thr Ala Ala Ile65 70 75 80Tyr Ala Ala Arg Ala Glu Leu Lys Pro Leu Leu Phe Glu Gly Trp Met85 90 95Ala Asn Asp Ile Ala Pro Gly Gly Gln Leu Thr Thr Thr Thr Asp Val100 105 110Glu Asn Phe Pro Gly Phe Pro Glu Gly Ile Leu Gly Val Glu Leu Thr115 120 125Asp Lys Phe Arg Lys Gln Ser Glu Arg Phe Gly Thr Thr Ile Phe Thr130 135 140Glu Thr Val Thr Lys Val Asp Phe Ser Ser Lys Pro Phe Lys Leu Phe145 150 155 160Thr Asp Ser Lys Ala Ile Leu Ala Asp Ala Val Ile Leu Ala Thr Gly165 170 175Ala Val Ala Lys Arg Leu Ser Phe Val Gly Ser Gly Glu Gly Ser Gly180 185 190Gly Phe Trp Asn Arg Gly Ile Ser Ala Cys Ala Val Cys Asp Gly Ala195 200 205Ala Pro Ile Phe Arg Asn Lys Pro Leu Ala Val Ile Gly Gly Gly Asp210 215 220Ser Ala Met Glu Glu Ala Asn Phe Leu Thr Lys Tyr Gly Ser Lys Val225 230 235 240Tyr Ile Ile His Arg Arg Asp Ala Phe Arg Ala Ser Lys Ile Met Gln245 250 255Gln Arg Ala Leu Ser Asn Pro Lys Ile Asp Val Ile Trp Asn Ser Ser260 265 270Val Val Glu Ala Tyr Gly Asp Gly Glu Arg Asp Val Leu Gly Gly Leu275 280 285Lys Val Lys Asn Val Val Thr Gly Asp Val Ser Asp Leu Lys Val Ser290 295 300Gly Leu Phe Phe Ala Ile Gly His Glu Pro Ala Thr Lys Phe Leu Asp305 310 315 320Gly Gly Val Glu Leu Asp Ser Asp Gly Tyr Val Val Thr Lys Pro Gly325 330 335Thr Thr Gln Thr Ser Val Pro Gly Val Phe Ala Ala Gly Asp Val Gln340 345 350Asp Lys Lys Tyr Arg Gln Ala Ile Thr Ala Ala Gly Thr Gly Cys Met355 360 365Ala Ala Leu Asp Ala Glu His Tyr Leu Gln Glu Ile Ala Gly Ser Lys370 375 380Ala Asn Glu Thr Thr Glu Glu Thr Gly Asp Val Asp Ser Thr Asp Thr385 390 395 400Thr Asp Trp Ser Thr Ala Met Glu Glu Gly Gln Val Ile Ala Cys His405 410 415Thr Val Glu Thr Trp Asn Glu Gln Leu Gln Lys Ala Asn Glu Ser Lys420 425 430Thr Leu Val Val Val Asp Phe Thr Ala Ser Trp Cys Gly Pro Cys Arg435 440 445Phe Ile Ala Pro Phe Phe Ala Asp Leu Ala Lys Lys Leu Pro Asn Val450 455 460Leu Phe Leu Lys Val Asp Thr Asp Glu Leu Lys Ser Val Ala Ser Asp465 470 475 480Trp Ala Ile Gln Ala Met Pro Thr Phe Met Phe Leu Lys Glu Gly Lys485 490 495Ile Leu Asp Lys Val Val Gly Ala Lys Lys Asp Glu Leu Gln Ser Thr500 505 510Ile Ala Lys His Leu Ala51521036211458212PRT213麻瘋分枝桿菌(Mycobacterium leprae)40036Met Asn Thr Thr Pro Ser Ala His Glu Thr Ile His Glu Val Ile Val1 5 10 15Ile Gly Ser Gly Pro Ala Gly Tyr Thr Ala Ala Leu Tyr Ala Ala Arg20 25 30Ala Gln Leu Thr Pro Leu Val Phe Glu Gly Thr Ser Phe Gly Gly Ala
35 40 45Leu Met Thr Thr Thr Glu Val Glu Asn Tyr Pro Gly Phe Arg Asn Gly50 55 60Ile Thr Gly Pro Glu Leu Met Asp Asp Met Arg Glu Gln Ala Leu Arg65 70 75 80Phe Gly Ala Glu Leu Arg Thr Glu Asp Val Glu Ser Val Ser Leu Arg85 90 95Gly Pro Ile Lys Ser Val Val Thr Ala Glu Gly Gln Thr Tyr Gln Ala100 105 110Arg Ala Val Ile Leu Ala Met Gly Thr Ser Val Arg Tyr Leu Gln Ile115 120 125Pro Gly Glu Gln Glu Leu Leu Gly Arg Gly Val Ser Ala Cys Ala Thr130 135 140Cys Asp Gly Ser Phe Phe Arg Gly Gln Asp Ile Ala Val Ile Gly Gly145 150 155 160Gly Asp Ser Ala Met Glu Glu Ala Leu Phe Leu Thr Arg Phe Ala Arg165 170 175Ser Val Thr Leu Val His Arg Arg Asp Glu Phe Arg Ala Ser Lys Ile180 185 190Met Leu Gly Arg Ala Arg Asn Asn Asp Lys Ile Lys Phe Ile Thr Asn195 200 205His Thr Val Val Ala Val Asn Gly Tyr Thr Thr Val Thr Gly Leu Arg210 215 220Leu Arg Asn Thr Thr Thr Gly Glu Glu Thr Thr Leu Val Val Thr Gly225 230 235 240Val Phe Val Ala Ile Gly His Glu Pro Arg Ser Ser Leu Val Ser Asp245 250 255Val Val Asp Ile Asp Pro Asp Gly Tyr Val Leu Val Lys Gly Arg Thr260 265 270Thr Ser Thr Ser Met Asp Gly Val Phe Ala Ala Gly Asp Leu Val Asp275 280 285Arg Thr Tyr Arg Gln Ala Ile Thr Ala Ala Gly Ser Gly Cys Ala Ala290 295 300Ala Ile Asp Ala Glu Arg Trp Leu Ala Glu His Ala Gly Ser Lys Ala305 310 315 320Asn Glu Thr Thr Glu Glu Thr Gly Asp Val Asp Ser Thr Asp Thr Thr325 330 335Asp Trp Ser Thr Ala Met Thr Asp Ala Lys Asn Ala Gly Val Thr Ile340 345 350Glu Val Thr Asp Ala Ser Phe Phe Ala Asp Val Leu Ser Ser Asn Lys355 360 365Pro Val Leu Val Asp Phe Trp Ala Thr Trp Cys Gly Pro Cys Lys Met370 375 380Val Ala Pro Val Leu Glu Glu Ile Ala Ser Glu Gln Arg Asn Gln Leu385 390 395 400Thr Val Ala Lys Leu Asp Val Asp Thr Asn Pro Glu Met Ala Arg Glu405 410 415Phe Gln Val Val Ser Ile Pro Thr Met Ile Leu Phe Gln Gly Gly Gln420 425 430Pro Val Lys Arg Ile Val Gly Ala Lys Gly Lys Ala Ala Leu Leu Arg435 440 445Asp Leu Ser Asp Val Val Pro Asn Leu Asn45045521037211471212PRT213鼠耳芥220223嵌合40037Met Asn Gly Leu Glu Thr His Asn Thr Arg Leu Cys Ile Val Gly Ser1 5 10 15Gly Pro Ala Ala His Thr Ala Ala Ile TyT Ala Ala Arg Ala Glu Leu
20 25 30Lys Pro Leu Leu Phe Glu Gly Trp Met Ala Asn Asp Ile Ala Pro Gly35 40 45Gly Gln Leu Thr Thr Thr Thr Asp Val Glu Asn Phe Pro Gly Phe Pro50 55 60Glu Gly Ile Leu Gly Val Glu Leu Thr Asp Lys Phe Arg Lys Gln Ser65 70 75 80Glu Arg Phe Gly Thr Thr Ile Phe Thr Glu Thr Val Thr Lys Val Asp85 90 95Phe Ser Ser Lys Pro Phe Lys Leu Phe Thr Asp Ser Lys Ala Ile Leu100 105 110Ala Asp Ala Val Ile Leu Ala Thr Gly Ala Val Ala Lys Arg Leu Ser115 120 125Phe Val Gly Ser Gly Glu Gly Ser Gly Gly Phe Trp Asn Arg Gly Ile130 135 140Ser Ala Cys Ala Val Cys Asp Gly Ala Ala Pro Ile Phe Arg Asn Lys145 150 155 160Pro Leu Ala Val Ile Gly Gly Gly Asp Ser Ala Met Glu Glu Ala Asn165 170 175Phe Leu Thr Lys Tyr Gly Ser Lys Val Tyr Ile Ile His Arg Arg Asp180 185 190Ala Phe Arg Ala Ser Lys Ile Met Gln Gln Arg Ala Leu Ser Asn Pro195 200 205Lys Ile Asp Val Ile Trp Asn Ser Ser Val Val Glu Ala Tyr Gly Asp210 215 220Gly Glu Arg Asp Val Leu Gly Gly Leu Lys Val Lys Asn Val Val Thr225 230 235 240Gly Asp Val Ser Asp Leu Lys Val Ser Gly Leu Phe Phe Ala Ile Gly245 250 255His Glu Pro Ala Thr Lys Phe Leu Asp Gly Gly Val Glu Leu Asp Ser260 265 270Asp Gly Tyr Val Val Thr Lys Pro Gly Thr Thr Gln Thr Ser Val Pro275 280 285Gly Val Phe Ala Ala Gly Asp Val Gln Asp Lys Lys Tyr Arg Gln Ala290 295 300Ile Thr Ala Ala Gly Thr Gly Cys Met Ala Ala Leu Asp Ala Glu His305 310 315 320Tyr Leu Gln Glu Ile Ala Gly Ser Lys Ala Asn Glu Thr Thr Glu Glu325 330 335Thr Gly Asp Val Asp Ser Thr Asp Thr Thr Asp Trp Ser Thr Ala Met340 345 350Glu Glu Gly Gln Val Ile Ala Cys Glu Glu Gly Gln Val Ile Ala Cys355 360 365His Thr Val Glu Thr Trp Asn Glu Gln Leu Gln Lys Ala Asn Glu Ser370 375 380Lys Thr Leu Val Val Val Asp Phe Thr Ala Ser Trp Cys Gly Pro Cys385 390 395 400Arg Phe Ile Ala Pro Phe Phe Ala Asp Leu Ala Lys Lys Leu Pro Asn405 410 415Val Leu Phe Leu Lys Val Asp Thr Asp Glu Leu Lys Ser Val Ala Ser420 425 430Asp Trp Ala Ile Gln Ala Met Pro Thr Phe Met Phe Leu Lys Glu Gly435 440 445Lys Ile Leu Asp Lys Val Val Gly Ala Lys Lys Asp Glu Leu Gln Ser450 455 460Thr Ile Ala Lys His Leu Ala465 47021038211345212DNA213鼠耳芥220221CDS222(1)...(345)40038atg gct tcg gaa gaa gga caa gtg atc gcc tgc cac acc gtt gag aca 48Met Ala Ser Glu Glu Gly Gln Val Ile Ala Cys His Thr Val Glu Thr1 5 10 15tgg sac gag cag ctt cag aag gct aat gaa tcc aaa act ctt gtg gtg 96Trp Asn Glu Gln Leu Gln Lys Ala Asn Glu Ser Lys Thr Leu Val Val20 25 30gtt gat ttc acg gct tct tgg tgt gga cca tgt cgt ttc atc gct cca 144Val Asp Phe Thr Ala Ser Trp Cys Gly Pro Cys Arg Phe Ile Ala Pro35 40 45ttc ttt gct gat ttg gct aag aaa ctt cct aac gtg ctt ttc ctc aag 192Phe Phe Ala Asp Leu Ala Lys Lys Leu Pro Asn Val Leu Phe Leu Lys50 55 60gtt gat act gat gaa ttg aag tcg gtg gca agt gat tgg gcg ata cag 240Val Asp Thr Asp Glu Leu Lys Ser Val Ala Ser Asp Trp Ala Ile Gln65 70 75 80gcg atg cca acc ttc atg ttt ttg aag gaa ggg aag att ttg gac aaa 288Ala Met Pro Thr Phe Met Phe Leu Lys Glu Gly Lys Ile Leu Asp Lys85 90 95gtt gtt gga gcc aag aaa gat gag ctt cag tct acc att gcc aaa cac 336Val Val Gly Ala Lys Lys Asp Glu Leu Gln Ser Thr Ile Ala Lys His100 105 110ttg gct taa 345Leu Ala *21039211114212PRT213鼠耳芥40039Met Ala Ser Glu Glu Gly Gln Val Ile Ala Cys His Thr Val Glu Thr1 5 10 15Trp Asn Glu Gln Leu Gln Lys Ala Asn Glu Ser Lys Thr Leu Val Val20 25 30Val Asp Phe Thr Ala Ger Trp Cys Gly Pro Cys Arg phe Ile Ala Pro35 40 45Phe Phe Ala Asp Leu Ala Lys Lys Leu Pro Asn Val Leu Phe Leu Lys50 55 60Val Asp Thr Asp Glu Leu Lys Ser Val Ala Ser Asp Trp Ala Ile Gln65 70 75 80Ala Met Pro Thr Phe Met Phe Leu Lys Glu Gly Lys Ile Leu Asp Lys85 90 95Val Val Gly Ala Lys Lys Asp Glu Leu Gln Ser Thr Ile Ala Lys His100 105 110Leu Ala21040211999212DNA213鼠耳芥220221CDS222(1)...(999)40040atg aat ggt ctc gaa act cac aac aca agg ctc tgt atc gta gga agt 48Met Asn Gly Leu Glu Thr His Asn Thr Arg Leu Cys Ile Val Gly Ser1 5 10 15ggc cca gcg gca cac acg gcg gcg att tac gca gct agg gct gaa ctt 96Gly Pro Ala Ala His Thr Ala Ala Ile Tyr Ala Ala Arg Ala Glu Leu20 25 30aaa cct ctt ctc ttc gaa gga tgg atg gct aac gac atc gct ccc ggt 144Lys Pro Leu Leu Phe Glu Gly Trp Met Ala Asn Asp Ile Ala Pro Gly35 40 45ggt caa ctc aac caa cca ccg cgt gag aat ttc ccc gga ttt cca gaa 192Gly Gln Leu Asn Gln Pro Pro Arg Glu Asn Phe Pro Gly Phe Pro Glu50 55 60ggt att ctc gga gta gag ctc act gac aaa ttc cgt aaa caa tcg gag 240Gly Ile Leu Gly Val Glu Leu Thr Asp Lys Phe Arg Lys Gln Ser Glu65 70 75 80cga ttc ggt act acg ata ttt aca gag acg gtg acg aaa gtc gat ttc 288Arg Phe Gly Thr Thr Ile Phe Thr Glu Thr Val Thr Lys Val Asp Phe85 90 95tct tcg aaa ccg ttt aag cta ttc aca gat tca aaa gcc att ctc gct 336Ser Ser Lys Pro Phe Lys Leu Phe Thr Asp Ser Lys Ala Ile Leu Ala100 105 110gac gct gtg att ctc gct atc gga gct gtg gct aag tgg ctt agc ttc 384Asp Ala Val Ile Leu Ala Ile Gly Ala Val Ala Lys Trp Leu Ser Phe115 120 125gtt gga tct ggt gaa gtt ctc gga ggt ttg tgg aac cgt gga atc tcc 432Val Gly Ser Gly Glu Val Leu Gly Gly Leu Trp Asn Arg Gly Ile Ser130 135 140gct tgt gct gtt tgc gac gga gct gct ccg ata ttc cgc aac aaa cct 480Ala Cys Ala Val Cys Asp Gly Ala Ala Pro Ile Phe Arg Asn Lys Pro145150 155 160ctt gcg gtg atc ggt gga ggc gat tct gca atg gaa gaa gca aac ttt 528Leu Ala Val Ile Gly Gly Gly Asp Ser Ala Met Glu Glu Ala Asn Phe165 170 175ctt aca aaa tat gga tct aaa gtg tat ata atc gat agg aga gat gct 576Leu Thr Lys Tyr Gly Ser Lys Val Tyr Ile Ile Asp Arg Arg Asp Ala180 185 190ttt aga gcg tct aag att atg cag cag cga gct ttg tct aat cct aag 624Phe Arg Ala Ser Lys Ile Met Gln Gln Arg Ala Leu Ser Asn Pro Lys195 200 205att gat gtg att tgg aac tcg tct gtt gtg gaa gct tat gga gat gga 672Ile Asp Val Ile Trp Asn Ser Ser Val Val Glu Ala Tyr Gly Asp Gly210 215 220gaa aga gat gtg ctt gga gga ttg aaa gtg aag aat gtg gtt acc gga 720Glu Arg Asp Val Leu Gly Gly Leu Lys Val Lys Asn Val Val Thr Gly225 230 235 240gat gtt tct gat tta aaa gtt tct gga ttg ttc ttt gct att ggt cat 768Asp Val Ser Asp Leu Lys Val Ser Gly Leu Phe Phe Ala Ile Gly His245 250 255gag cca gct acc aag ttt ttg gat ggt ggt gtt gag tta gat tcg gat 816Glu Pro Ala Thr Lys Phe Leu Asp Gly Gly Val Glu Leu Asp Ser Asp
260 265 270ggt tat gtt gtc acg aag cct ggt act aca cag act agc gtt ccc gga 864Gly Tyr Val Val Thr Lys Pro Gly Thr Thr Gln Thr Ser Val Pro Gly275 280 285gtt ttc gct gcg ggt gat gtt cag gat aag aag tat agg caa gcc atc 912Val Phe Ala Ala Gly Asp Val Gln Asp Lys Lys Tyr Arg Gln Ala Ile290 295 300act gct gca gga act ggg tgc atg gca gct ttg gat gca gag cat tac 960Thr Ala Ala Gly Thr Gly Cys Met Ala Ala Leu Asp Ala Glu His Tyr305 310 315 320tta caa gag att gga tct cag caa ggt aag agt gat tga 999Leu Gln Glu Ile Gly Ser Gln Gln Gly Lys Ser Asp *325 33021041211332212PRT213鼠耳芥40041Met Asn Gly Leu Glu Thr His Asn Thr Arg Leu Cys Ile Val Gly Ser1 5 10 15Gly Pro Ala Ala His Thr Ala Ala Ile Tyr Ala Ala Arg Ala Glu Leu20 25 30Lys Pro Leu Leu Phe Glu Gly Trp Met Ala Asn Asp Ile Ala Pro Gly35 40 45Gly Gln Leu Asn Gln Pro Pro Arg Glu Asn Phe Pro Gly Phe Pro Glu50 55 60Gly Ile Leu Gly Val Glu Leu Thr Asp Lys Phe Arg Lys Gln Ser Glu65 70 75 80Arg Phe Gly Thr Thr Ile Phe Thr Glu Thr Val Thr Lys Val Asp Phe85 90 95Ser Ser Lys Pro Phe Lys Leu Phe Thr Asp Ser Lys Ala Ile Leu Ala100 105 110Asp Ala Val Ile Leu Ala Ile Gly Ala Val Ala Lys Trp Leu Ser Phe115 120 125Val Gly Ser Gly Glu Val Leu Gly Gly Leu Trp Asn Arg Gly Ile Ser130 135 140Ala Cys Ala Val Cys Asp Gly Ala Ala Pro Ile Phe Arg Asn Lys Pro145 150 155 160Leu Ala Val Ile Gly Gly Gly Asp Ser Ala Met Glu Glu Ala Asn Phe165 170 175Leu Thr Lys Tyr Gly Ser Lys Val Tyr Ile Ile Asp Arg Arg Asp Ala180 185 190Phe Arg Ala Ser Lys Ile Met Gln Gln Arg Ala Leu Ser Asn Pro Lys195 200 205Ile Asp Val Ile Trp Asn Ser Ser Val Val Glu Ala Tyr Gly Asp Gly210 215 220Glu Arg Asp Val Leu Gly Gly Leu Lys Val Lys Asn Val Val Thr Gly225 230 235 240Asp Val Ser Asp Leu Lys Val Ser Gly Leu Phe Phe Ala Ile Gly His245 250 255Glu Pro Ala Thr Lys Phe Leu Asp Gly Gly Val Glu Leu Asp Ser Asp260 265 270Gly Tyr Val Val Thr Lys Pro Gly Thr Thr Gln Thr Ser Val Pro Gly275 280 285Val Phe Ala Ala Gly Asp Val Gln Asp Lys Lys Tyr Arg Gln Ala Ile290 295 300Thr Ala Ala Gly Thr Gly Cys Met Ala Ala Leu Asp Ala Glu His Tyr305 310 315 320Leu Gln Glu Ile Gly Ser Gln Gln Gly Lys Ser Asp325 33021042211332212DNA213大腸桿菌220221CDS222(1)...(332)40042atg agc gat aaa att att cac ctg act gac gac agt ttt gac acg gat 48Met Ser Asp Lys Ile Ile His Leu Thr Asp Asp Ser Phe Asp Thr Asp1 5 10 l5gta ctc aaa gcg gac ggg gct atc ctc gtt gat ttc tgg gca gag tgg 96Val Leu Lys Ala Asp Gly Ala Ile Leu Val Asp Phe Trp Ala Glu Trp20 25 30tgc ggg ccg tgt aaa atg atc gct ccg att ctg gat gaa atc gct gac 144Cys Gly pro Cys Lys Met Ile Ala pro Ile Leu Asp Glu Ile Ala Asp35 40 45gaa tat cag ggc aaa ttg acc gtt gcc aaa ctg aac att gac cag aac 192Glu Tyr Gln Gly Lys Leu Thr Val Ala Lys Leu Asn Ile Asp Gln Asn50 55 60cca ggt act gcg cct aaa tat ggc atc cgc ggt att ccg act ctg ctg 240Pro Gly Thr Ala Pro Lys Tyr Gly Ile Arg Gly Ile Pro Thr Leu Leu65 70 75 80ctg ttt aaa aac ggc gaa gtg gcg gca acc aaa gta ggc gca ctg tct 288Leu Phe Lys Asn Gly Glu Val Ala Ala Thr Lys Val Gly Ala Leu Ser85 90 95aaa ggt cag ttg aaa gag ttt ctc gac gcc aat ctg gcg taa ta 332Lys Gly Gln Leu Lys Glu Phe Leu Asp Ala Asn Leu Ala *100 10521043211109212PRT213大腸桿菌40043Met Ser Asp Lys Ile Ile His Leu Thr Asp Asp Ser Phe Asp Thr Asp1 5 10 15Val Leu Lys Ala Asp Gly Ala Ile Leu Val Asp Phe Trp Ala Glu Trp20 25 30Cys Gly Pro Cys Lys Met Ile Ala Pro Ile Leu Asp Glu Ile Ala Asp35 40 45Glu Tyr Gln Gly Lys Leu Thr Val Ala Lys Leu Asn Ile Asp Gln Asn50 55 60Pro Gly Thr Ala Pro Lys Tyr Gly Ile Arg Gly Ile Pro Thr Leu Leu657075 80Leu Phe Lys Asn Gly Glu Val Ala Ala Thr Lys Val Gly Ala Leu Ser85 90 95Lys Gly Gln Leu Lys Glu Phe Leu Asp Ala Asn Leu Ala100 10521044211966212DNA213大腸桿菌220221CDS222(1)...(966)40044atg ggc acg acc aaa cac agt aaa ctg ctt atc ctg ggt tca ggc ccg 48Met Gly Thr Thr Lys His Ser Lys Leu Leu Ile Leu Gly Ser Gly Pro1 5 10 15gcg gga tac acc gct gct gtc tac gcg gcg cgc gcc aac ctg caa cct 96Ala Gly Tyr Thr Ala Ala Val Tyr Ala Ala Arg Ala Asn Leu Gln Pro20 25 30gtg ctg att acc ggc atg gaa aaa ggc ggc caa ctg acc acc acc acg 144Val Leu Ile Thr Gly Met Glu Lys Gly Gly Gln Leu Thr Thr Thr Thr35 40 45gsa gtg gaa aac tgg cct ggc gat cca aac gat ctg acc ggt ccg tta 192Glu Val Glu Asn Trp Pro Gly Asp Pro Asn Asp Leu Thr Gly Pro Leu50 55 60tta atg gag cgc atg cac gaa cat gcc acc aag ttt gaa act gag atc 240Leu Met Glu Arg Met His Glu His Ala Thr Lys Phe Glu Thr Glu Ile65 70 75 80att ttt gat cat atc aac aag gtg gat ctg caa aac cgt ccg ttc cgt 288Ile Phe Asp His Ile Asn Lys Val Asp Leu Gln Asn Arg Pro Phe Arg85 90 95ctg aat ggc gat aac ggc gaa tac act tgc gac gcg ctg att att gcc 336Leu Asn Gly Asp Asn Gly Glu Tyr Thr Cys Asp Ala Leu Ile Ile Ala100 105 110acc gga gct tct gca cgc tat ctc ggc ctg ccc tct gaa gaa gcc ttt 384Thr Gly Ala Ser Ala Arg Tyr Leu Gly Leu Pro Ser Glu Glu Ala Phe115 120 125aaa ggc cgt ggg gtt tct gct tgt gca acc tgc gac ggt ttc ttc tat 432Lys Gly Arg Gly Val Ser Ala Cys Ala Thr Cys Asp Gly Phe Phe Tyr130 135 140cgc aac cag aaa gtt gcg gtc atc ggc ggc ggc aat acc gcg gtt gaa 480Arg Asn Gln Lys Val Ala Val Ile Gly Gly Gly Asn Thr Ala Val Glu145 150 155 160gag gcg ttg tat ctg tct aac atc gct tcg gaa gtg cat ctg att cac 528Glu Ala Leu Tyr Leu Ser Asn Ile Ala Ser Glu Val His Leu Ile His165 170 175cgc cgt gac ggt ttc cgc gcg gaa aaa atc ctc att aag cgc ctg atg 576Arg Arg Asp Gly Phe Arg Ala Glu Lys Ile Leu Ile Lys Arg Leu Met180 185 190gat aaa gtg gag aac ggc aac atc att ctg cac acc aac cgt acg ctg 624Asp Lys Val Glu Asn Gly Asn Ile Ile Leu His Thr Asn Arg Thr Leu195 200 205gaa gaa gtg acc ggc gat caa atg ggt gtc act ggc gtt cgt ctg cgc 672Glu Glu Val Thr Gly Asp Gln Met Gly Val Thr Gly Val Arg Leu Arg210 215 220gat acg caa aac agc gat aac atc gag tca ctc gac gtt gcc ggt ctg 720Asp Thr Gln Asn Ser Asp Asn Ile Glu Ser Leu Asp Val Ala Gly Leu225 230 235 240ttt gtt gct atc ggt cac agc ccg aat act gcg att ttc gaa ggg cag 768Phe Val Ala Ile Gly His Ser Pro Asn Thr Ala Ile Phe Glu Gly Gln
245 250 255ctg gaa ctg gaa aac ggc tac atc aaa gta cag tcg ggt att cat ggt 816Leu Glu Leu Glu Asn Gly Tyr Ile Lys Val Gln Ser Gly Ile His Gly260 265 270aat gcc acc cag acc agc att cct ggc gtc ttt gcc gca ggc gac gtg 864Asn Ala Thr Gln Thr Ser Ile Pro Gly Val Phe Ala Ala Gly Asp Val275 280 285atg gat cac att tat cgc cag gcc att act tcg gcc ggt aca ggc tgc 912Met Asp His Ile Tyr Arg Gln Ala Ile Thr Ser Ala Gly Thr Gly Cys290 295 300atg gca gca ctt gat gcg gaa cgc tac ctc gat ggt tta gct gac gca 960Met Ala Ala Leu Asp Ala Glu Arg Tyr Leu Asp Gly Leu Ala Asp Ala305 310315 320aaa taa 966Lys *21045211321212PRT213大腸桿菌40045Met Gly Thr Thr Lys His Ser Lys Leu Leu Ile Leu Gly Ser Gly Pro1 5 10 15Ala Gly Tyr Thr Ala Ala Val Tyr Ala Ala Arg Ala Asn Leu Gln Pro20 25 30Val Leu Ile Thr Gly Met Glu Lys Gly Gly Gln Leu Thr Thr Thr Thr35 40 45Glu Val Glu Asn Trp Pro Gly Asp Pro Asn Asp Leu Thr Gly Pro Leu50 55 60Leu Met Glu Arg Met His Glu His Ala Thr Lys Phe Glu Thr Glu Ile65 70 75 80Ile Phe Asp His Ile Asn Lys Val Asp Leu Gln Asn Arg Pro Phe Arg85 90 95Leu Asn Gly Asp Asn Gly Glu Tyr Thr Cys Asp Ala Leu Ile Ile Ala100 105 110Thr Gly Ala Ser Ala Arg Tyr Leu Gly Leu Pro Ser Glu Glu Ala Phe115 120 125Lys Gly Arg Gly Val Ser Ala Cys Ala Thr Cys Asp Gly Phe Phe Tyr130 135 140Arg Asn Gln Lys Val Ala Val Ile Gly Gly Gly Asn Thr Ala Val Glu145 150 155 160Glu Ala Leu Tyr Leu Ser Asn Ile Ala Ser Glu Val His Leu Ile His165 170 175Arg Arg Asp Gly Phe Arg Ala Glu Lys Ile Leu Ile Lys Arg Leu Met180 185 190Asp Lys Val Glu Asn Gly Asn Ile Ile Leu His Thr Asn Arg Thr Leu195 200 205Glu Glu Val Thr Gly Asp Gln Met Gly Val Thr Gly Val Arg Leu Arg210 215 220Asp Thr Gln Asn Ser Asp Asn Ile Glu Ser Leu Asp Val Ala Gly Leu225 230 235 240Phe Val Ala Ile Gly His Ser Pro Asn Thr Ala Ile Phe Glu Gly Gln245 250 255Leu Glu Leu Glu Asn Gly Tyr Ile Lys Val Gln Ser Gly Ile His Gly260 265 270Asn Ala Thr Gln Thr Ser Ile Pro Gly Val Phe Ala Ala Gly Asp Val275 280 285Met Asp His Ile Tyr Arg Gln Ala Ile Thr Ser Ala Gly Thr Gly Cys290 295 300Met Ala Ala Leu Asp Ala Glu Arg Tyr Leu Asp Gly Leu Ala Asp Ala305 310 315 320Lys21046211318212DNA213人(Homo Sapien)220221CDS222(1)...(318)40046atg gtg aag cag atc gag agc aag act gct ttt cag gaa gcc ttg gac 48Met Val Lys Gln Ile Glu Ser Lys Thr Ala Phe Gln Glu Ala Leu Asp1 5 10 15gct gca ggt gat aaa ctt gta gta gtt gac ttc tca gcc acg tgg tgt 96Ala Ala Gly Asp Lys Leu Val Val Val Asp Phe Ser Ala Thr Trp Cys20 25 30ggg cct tgc aaa atg atc aag cct ttc ttt cat tcc ctc tct gaa aag 144Gly Pro Cys Lys Met Ile Lys Pro Phe Phe His Ser Leu Ser Glu Lys35 40 45tat tcc aac gtg ata ttc ctt gaa gta gat gtg gat gac tgt cag gat 192Tyr Ser Asn Val Ile Phe Leu Glu Val Asp Val Asp Asp Cys Gln Asp50 55 60gtt gct tca gag tgt gaa gtc aaa tgc atg cca aca ttc cag ttt ttt 240Val Ala Ser Glu Cys Glu Val Lys Cys Met Pro Thr Phe Gln Phe Phe65 70 75 80aag aag gga caa aag gtg ggt gaa ttt tct gga gcc aat aag gaa aag 288Lys Lys Gly Gln Lys Val Gly Glu Phe Ser Gly Ala Asn Lys Glu Lys85 90 95ctt gaa gcc acc att aat gaa tta gtc taa 318Leu Glu Ala Thr Ile Asn Glu Leu Val *10010521047211105212PRT213人40047Met Val Lys Gln Ile Glu Ser Lys Thr Ala Phe Gln Glu Ala Leu Asp1 5 10 15Ala Ala Gly Asp Lys Leu Val Val Val Asp Phe Ser Ala Thr Trp Cys20 25 30Gly Pro Cys Lys Met Ile Lys Pro Phe Phe His Ser Leu Ser Glu Lys35 40 45Tyr Ser Asn Val Ile Phe Leu Glu Val Asp Val Asp Asp Cys Gln Asp50 55 60Val Ala Ser Glu Cys Glu Val Lys Cys Met Pro Thr Phe Gln Phe Phe65 70 75 80Lys Lys Gly Gln Lys Val Gly Glu Phe Ser Gly Ala Asn Lys Glu Lys85 90 95Leu Glu Ala Thr Ile Asn Glu Leu Val100 105210482111494212DNA213人220221CDS222(1)...(1494)40048atg aac ggc cct gaa gat ctt ccc aag tcc tat gac tat gac ctt atc 48Met Asn Gly Pro Glu Asp Leu Pro Lys Ser Tyr Asp Tyr Asp Leu Ile1 5 10 15atc att gga ggt ggc tca gga ggt ctg gca gct gct aag gag cca gcc 96Ile Ile Gly Gly Gly Ser Gly Gly Leu Ala Ala Ala Lys Glu Pro Ala20 25 30caa tat ggc aag aag gtg atg gtc ctg gac ttt ggc act ccc acc cct 144Gln Tyr Gly Lys Lys Val Met Val Leu Asp Phe Gly Thr Pro Thr Pro35 40 45ctt gga act aga tgg ggt ctt gga gga aca tgt gtg aat gtg ggt tgc 192Leu Gly Thr Arg Trp Gly Leu Gly Gly Thr Cys Val Asn Val Gly Cys50 55 60ata cct aaa aaa ctg atg cat caa gca gct ttg tta gga caa gcc ctg 240Ile Pro Lys Lys Leu Met His Gln Ala Ala Leu Leu Gly Gln Ala Leu65 70 75 80caa gac tct cga aat tat gga tgg aaa gtc gag gag aca gtt aag cat 288Gln Asp Ser Arg Asn Tyr Gly Trp Lys Val Glu Glu Thr Val Lys His85 90 95gat tgg gac aga atg ata gaa gct gta cag aat cac att ggc tct ttg 336Asp Trp Asp Arg Met Ile Glu Ala Val Gln Asn His Ile Gly Ser Leu100 105 110aat tgg ggc tac cga gta gct ctg cgg gag aaa aaa gtc gtc tat gag 384Asn Trp Gly Tyr Arg Val Ala Leu Arg Glu Lys Lys Val Val Tyr Glu115 120 125aat gct tat ggg caa ttt att ggt cct cac agg att aag gca aca aat 432Asn Ala Tyr Gly Gln Phe Ile Gly Pro His Arg Ile Lys Ala Thr Asn130 135 140aat aaa ggc aaa gaa aaa att tat tca gca gag aga ttt ctc att gcc 480Asn Lys Gly Lys Glu Lys Ile Tyr Ser Ala Glu Arg Phe Leu Ile Ala145 150 155 160act ggt gaa aga cca cgt tac ttg ggc atc cct ggt gac aaa gaa tac 528Thr Gly Glu Arg Pro Arg Tyr Leu Gly Ile Pro Gly Asp Lys Glu Tyr165 170 175tgc atc agc agt gat gat ctt ttc tcc ttg cct tac tgc ccg ggt aag 576Cys Ile Ser Ser Asp Asp Leu Phe Ser Leu Pro Tyr Cys Pro Gly Lys180 185 190aca ctg gtt gtt gga gca tcc tat gtc gct ttg gag tgc gct gga ttt 624Thr Leu Val Val Gly Ala Ser Tyr Val Ala Leu Glu Cys Ala Gly Phe195 200 205ctt gct ggt att ggt tta gac gtc act gtt atg gtt agg tcc att ctt 672Leu Ala Gly Ile Gly Leu Asp Val Thr Val Met Val Arg Ser Ile Leu210 215 220ctt aga gga ttt gac cag gac atg gcc aac aaa att ggt gaa cac atg 720Leu Arg Gly Phe Asp Gln Asp Met Ala Asn Lys Ile Gly Glu His Met225 230 235 240gaa gaa cat ggc atc aag ttt ata aga cag ttc gta cca att aaa gtt 768Glu Glu His Gly Ile Lys Phe Ile Arg Gln Phe Val Pro Ile Lys Val245 250 255gaa caa att gaa gca ggg aca cca ggc cga ctc aga gta gta gct cag 816Glu Gln Ile Glu Ala Gly Thr Pro Gly Arg Leu Arg Val Val Ala Gln260 265 270tcc acc aat agt gag gaa atc att gaa gga gaa tat aat acg gtg atg 864Ser Thr Asn Ser Glu Glu Ile Ile Glu Gly Glu Tyr Asn Thr Val Met275 280 285ctg gca ata gga aga gat gct tgc aca aga aaa att ggc tta gaa acc 912Leu Ala Ile Gly Arg Asp Ala Cys Thr Arg Lys Ile Gly Leu Glu Thr290 295 300gta ggg gtg aag ata aat gaa aag act gga aaa ata cct gtc aca gat 960Val Gly Val Lys Ile Asn Glu Lys Thr Gly Lys Ile Pro Val Thr Asp305 310 315 320gaa gaa cag acc aat gtg cct tac atc tat gcc att ggc gat ata ttg 1008Glu Glu Gln Thr Asn Val Pro Tyr Ile Tyr Ala Ile Gly Asp Ile Leu325 330 335gag gat aag gtg gag ctc acc cca gtt gca atc cag gca gga aga ttg 1056Glu Asp Lys Val Glu Leu Thr Pro Val Ala Ile Gln Ala Gly Arg Leu340 345 350ctg gct cag agg ctc tat gca ggt tcc act gtc aag tgt gac tat gaa 1104Leu Ala Gln Arg Leu Tyr Ala Gly Ser Thr Val Lys Cys Asp Tyr Glu355 360 365aat gtt cca acc act gta ttt act cct ttg gaa tat ggt gct tgt ggc 1152Asn Val Pro Thr Thr Val Phe Thr Pro Leu Glu Tyr Gly Ala Cys Gly370 375 380ctt tct gag gag aaa gct gtg gag aag ttt ggg gaa gaa aat att gag 1200Leu Ser Glu Glu Lys Ala Val Glu Lys Phe Gly Glu Glu Asn Ile Glu385 390 395 400gtt tac cat agt tac ttt tgg cca ttg gaa tgg acg att ccg tca aga 1248Val Tyr His Ser Tyr Phe Trp Pro Leu Glu Trp Thr Ile Pro Ser Arg405 410 415gat aac aac aaa tgt tat gca aaa ata atc tgt aat act aaa gac aat 1296Asp Asn Asn Lys Cys Tyr Ala Lys Ile Ile Cys Asn Thr Lys Asp Asn420 425 430gaa cgt gtt gtg ggc ttt cac gta ctg ggt cca aat gct gga gaa gtt 1344Glu Arg Val Val Gly Phe His Val Leu Gly Pro Asn Ala Gly Glu Val435 440 445aca caa ggc ttt gca gct gcg ctc aaa tgt gga ctg acc aaa aag cag 1392Thr Gln Gly Phe Ala Ala Ala Leu Lys Cys Gly Leu Thr Lys Lys Gln450 455 460ctg gac agc aca att gga atc cac cct gtc tgt gca gag gta ttc aca 1440Leu Asp Ser Thr Ile Gly Ile His Pro Val Cys Ala Glu Val Phe Thr465 470 475 480aca ttg tct gtg acc aag cgc tct ggg gca agc atc ctc cag gct ggc 1488Thr Leu Ser Val Thr Lys Arg Ser Gly Ala Ser Ile Leu Gln Ala Gly485 490 495tgc tga1494Cys *21049211497212PRT213人40049Met Asn Gly Pro Glu Asp Leu Pro Lys Ser Tyr Asp Tyr Asp Leu Ile1 5 10 15Ile Ile Gly Gly Gly Ser Gly Gly Leu Ala Ala Ala Lys Glu Pro Ala20 25 30Gln Tyr Gly Lys Lys Val Met Val Leu Asp Phe Gly Thr Pro Thr Pro35 40 45Leu Gly Thr Arg Trp Gly Leu Gly Gly Thr Cys Val Asn Val Gly Cys50 55 60Ile Pro Lye Lys Leu Met His Gln Ala Ala Leu Leu Gly Gln Ala Leu65 70 75 80Gln Asp Ser Arg Asn Tyr Gly Trp Lys Val Glu Glu Thr Val Lys His85 90 95Asp Trp Asp Arg Met Ile Glu Ala Val Gln Asn His Ile Gly Ser Leu100 105 110Asn Trp Gly Tyr Arg Val Ala Leu Arg Glu Lys Lys Val Val Tyr Glu115 120 125Asn Ala Tyr Gly Gln Phe Ile Gly Pro His Arg Ile Lys Ala Thr Asn130 135 140Asn Lys Gly Lys Glu Lys Ile Tyr Ser Ala Glu Arg Phe Leu Ile Ala145 150 155 160Thr Gly Glu Arg Pro Arg Tyr Leu Gly Ile Pro Gly Asp Lys Glu Tyr165 170 175Cys Ile Ser Ser Asp Asp Leu Phe Ser Leu Pro Tyr Cys Pro Gly Lys180 185 190Thr Leu Val Val Gly Ala Ser Tyr Val Ala Leu Glu Cys Ala Gly Phe195 200 205Leu Ala Gly Ile Gly Leu Asp Val Thr Val Met Val Arg Ser Ile Leu210 215 220Leu Arg Gly Phe Asp Gln Asp Met Ala Asn Lys Ile Gly Glu His Met225 230 235 240Glu Glu His Gly Ile Lys Phe Ile Arg Gln Phe Val Pro Ile Lys Val245 250 255Glu Gln Ile Glu Ala Gly Thr Pro Gly Arg Leu Arg Val Val Ala Gln260 265 270Ser Thr Asn Ser Glu Glu Ile Ile Glu Gly Glu Tyr Asn Thr Val Met275 280 285Leu Ala Ile Gly Arg Asp Ala Cys Thr Arg Lys Ile Gly Leu Glu Thr290 295 300Val Gly Val Lys Ile Asn Glu Lys Thr Gly Lys Ile Pro Val Thr Asp305 310 315 320Glu Glu Gln Thr Asn Val Pro Tyr Ile Tyr Ala Ile Gly Asp Ile Leu325 330 335Glu Asp Lys Val Glu Leu Thr Pro Val Ala Ile Gln Ala Gly Arg Leu340 345 350Leu Ala Gln Arg Leu Tyr Ala Gly Ser Thr Val Lys Cys Asp Tyr Glu355 360 365Asn Val Pro Thr Thr Val Phe Thr Pro Leu Glu Tyr Gly Ala Cys Gly370 375 380Leu Ser Glu Glu Lys Ala Val Glu Lys Phe Gly Glu Glu Asn Ile Glu385 390 395 400Val Tyr His Ser Tyr Phe Trp Pro Leu Glu Trp Thr Ile Pro Ser Arg405 410 415Asp Asn Asn Lys Cys Tyr Ala Lys Ile Ile Cys Asn Thr Lys Asp Asn420 425 430Glu Arg Val Val Gly Phe His Val Leu Gly Pro Asn Ala Gly Glu Val435 440 445Thr Gln Gly Phe Ala Ala Ala Leu Lys Cys Gly Leu Thr Lys Lys Gln450 455 460Leu Asp Ser Thr Ile Gly Ile His Pro Val Cys Ala Glu Val Phe Thr465 470 475 480Thr Leu Ser Val Thr Lys Arg Ser Gly Ala Ser Ile Leu Gln Ala Gly485 490 495Cys210502111377212DNA213麻瘋分枝桿菌220221CDS222(1)...(1377)40050atg aac acc act cct tct gcg cat gag acg ata cac gaa gtg atc gtt 48Met Asn Thr Thr Pro Ser Ala His Glu Thr Ile His Glu Val Ile Val1 5 10 15att ggc tcc ggt cca gca ggc tac act gct gcc ctg tac gcc gct cgt 96Ile Gly Ser Gly Pro Ala Gly Tyr Thr Ala Ala Leu Tyr Ala Ala Arg20 25 30gca cag cta aca ccg ctg gta ttt gag ggt acc tca ttc ggc ggc gcg 144Ala Gln Leu Thr Pro Leu Val Phe Glu Gly Thr Ser Phe Gly Gly Ala35 40 45ctg atg acc acc acc gag gtg gaa aac tac cca ggt ttt cgc aac ggc 192Leu Met Thr Thr Thr Glu Val Glu Asn Tyr Pro Gly Phe Arg Asn Gly50 55 60ata acc ggc ccg gag ttg atg gac gat atg cgt gaa cag gca ctg cga 240Ile Thr Gly Pro Glu Leu Met Asp Asp Met Arg Glu Gln Ala Leu Arg65 70 75 80ttc ggc gcg gaa ctg cgg acc gaa gac gtc gag tcg gta tca ttg cgt 288Phe Gly Ala Glu Leu Arg Thr Glu Asp Val Glu Ser Val Ser Leu Arg85 90 95ggc ccg atc aaa tcg gtc gtc acc gct gaa gga cag act tat cag gcc 336Gly Pro Ile Lys Ser Val Val Thr Ala Glu Gly Gln Thr Tyr Gln Ala100 105 110cga gcc gtc atc ctc gcc atg ggt acc tcc gtg cgt tat cta cag atc 384Arg Ala Val Ile Leu Ala Met Gly Thr Ser Val Arg Tyr Leu Gln Ile115 120 125ccc ggc gag caa gaa ttg cta gga cgt ggc gtg agt gca tgc gcg acc 432Pro Gly Glu Gln Glu Leu Leu Gly Arg Gly Val Ser Ala Cys Ala Thr130 135 140tgc gac ggg tcc ttt ttc cgc ggc caa gac att gcc gtc att ggc ggt 480Cys Asp Gly Ser Phe Phe Arg Gly Gln Asp Ile Ala Val Ile Gly Gly145 150 155 160gga gac tca gcg atg gag gaa gcc ctc ttt ttg acc cgg ttc gcc cgc 528Gly Asp Ser Ala Met Glu Glu Ala Leu Phe Leu Thr Arg Phe Ala Arg165 170 175agc gtc acg ctc gtg cac cgc cgc gac gaa ttc cga gct tct aag atc 576Ser Val Thr Leu Val His Arg Arg Asp Glu Phe Arg Ala Ser Lys Ile180 185 190atg ctc ggt cgc gcc cgt aac aat gac aag atc aaa ttc atc acc aac 624Met Leu Gly Arg Ala Arg Asn Asn Asp Lys Ile Lys Phe Ile Thr Asn195 200 205cac acc gtg gtc gcg gtg aac ggg tat aca aca gtg acc gga ttg cgg 672His Thr Val Val Ala Val Asn Gly Tyr Thr Thr Val Thr Gly Leu Arg210 215 220ttg cgt aac acc aca acg gga gag gaa acc acg cta gta gtg acc ggg 720Leu Arg Asn Thr Thr Thr Gly Glu Glu Thr Thr Leu Val Val Thr Gly225 230 235 240gtt ttt gtt gca att ggc cat gaa cca cgt tcc agc ctg gtg agc gat 768Val Phe Val Ala Ile Gly His Glu Pro Arg Ser Ser Leu Val Ser Asp245 250 255gtc gtc gac ata gac ccg gat ggc tac gtc ctg gtg aaa gga cgt acg 816Val Val Asp Ile Asp Pro Asp Gly Tyr Val Leu Val Lys Gly Arg Thr260 265 270acg agt aca tcg atg gac ggc gtt ttt gcg gcc ggc gac ctg gta gat 864Thr Ser Thr Ser Met Asp Gly Val Phe Ala Ala Gly Asp Leu Val Asp275 280 285cgc acc tac cgg cag gcg atc act gcc gca ggt agt ggc tgt gcc gcc 912Arg Thr Tyr Arg Gln Ala Ile Thr Ala Ala Gly Ser Gly Cys Ala Ala290 295 300gcc atc gac gcc gaa cgt tgg ttg gcg gag cat gcc ggg tca aaa gct 960Ala Ile Asp Ala Glu Arg Trp Leu Ala Glu His Ala Gly Ser Lys Ala305 310 315 320aac gaa aca aca gag gaa act gga gac gtt gac agt acc gac aca acc 1008Asn Glu Thr Thr Glu Glu Thr Gly Asp Val Asp Ser Thr Asp Thr Thr325 330 335gat tgg agc act gcg atg act gac gcc aag aac gcc ggg gtc aca ata 1056Asp Trp Ser Thr Ala Met Thr Asp Ala Lys Asn Ala Gly Val Thr Ile340 345 350gaa gtg acc gat gct tcc ttt ttc gca gac gtc tta tcc agt aat aag 1104Glu Val Thr Asp Ala Ser Phe Phe Ala Asp Val Leu Ser Ser Asn Lys355 360 365cct gtg tta gtt gat ttt tgg gca aca tgg tgt gga ccc tgc aag atg 1152Pro Val Leu Val Asp Phe Trp Ala Thr Trp Cys Gly Pro Cys Lys Met370 375 380gta gcg ccg gta ctc gaa gag atc gcg tcc gaa caa cga aac cag ctc 1200Val Ala Pro Val Leu Glu Glu Ile Ala Ser Glu Gln Arg Asn Gln Leu385 390 395 400act gtc gcc aag tta gat gta gac acc aac ccg gaa atg gca cgc gag 1248Thr Val Ala Lys Leu Asp Val Asp Thr Asn Pro Glu Met Ala Arg Glu405 410 415ttc cag gtc gtg tcg ata ccc aca atg att ctg ttc cag ggt ggc caa 1296Phe Gln Val Val Ser Ile Pro Thr Met Ile Leu Phe Gln Gly Gly Gln420 425 430cca gta aaa cgc atc gtt ggc gct aag ggc aaa gca gcg tta cta cgt 1344Pro Val Lys Arg Ile Val Gly Ala Lys Gly Lys Ala Ala Leu Leu Arg435 440 445gac ctt tcc gac gtg gta cct aac ctc aat tag 1377Asp Leu Ser Asp Val Val Pro Asn Leu Asn *
450 45521051211458212PRT213麻瘋分枝桿菌40051Met Asn Thr Thr Pro Ser Ala His Glu Thr Ile His Glu Val Ile Val1 5 10 15Ile Gly Ser Gly Pro Ala Gly Tyr Thr Ala Ala Leu Tyr Ala Ala Arg20 25 30Ala Gln Leu Thr Pro Leu Val Phe Glu Gly Thr Ser Phe Gly Gly Ala35 40 45Leu Met Thr Thr Thr Glu Val Glu Asn Tyr Pro Gly Phe Arg Asn Gly50 55 60Ile Thr Gly Pro Glu Leu Met Asp Asp Met Arg Glu Gln Ala Leu Arg65 70 75 80Phe Gly Ala Glu Leu Arg Thr Glu Asp Val Glu Ser Val Ser Leu Arg85 90 95Gly Pro Ile Lys Ser Val Val Thr Ala Glu Gly Gln Thr Tyr Gln Ala100 105 110Arg Ala Val Ile Leu Ala Met Gly Thr Ser Val Arg Tyr Leu Gln Ile115 120 125Pro Gly Glu Gln Glu Leu Leu Gly Arg Gly Val Ser Ala Cys Ala Thr130 135 140Cys Asp Gly Ser Phe Phe Arg Gly Gln Asp Ile Ala Val Ile Gly Gly145 150 155 160Gly Asp Ser Ala Met Glu Glu Ala Leu Phe Leu Thr Arg Phe Ala Arg165 170 175Ser Val Thr Leu Val His Arg Arg Asp Glu Phe Arg Ala Ser Lys Ile180 185 190Met Leu Gly Arg Ala Arg Asn Asn Asp Lys Ile Lys Phe Ile Thr Asn195 200 205His Thr Val Val Ala Val Asn Gly Tyr Thr Thr Val Thr Gly Leu Arg210 215 220Leu Arg Asn Thr Thr Thr Gly Glu Glu Thr Thr Leu Val Val Thr Gly225 230 235 240Val Phe Val Ala Ile Gly His Glu Pro Arg Ser Ser Leu Val Ser Asp245 250 255Val Val Asp Ile Asp Pro Asp Gly Tyr Val Leu Val Lys Gly Arg Thr260 265 270Thr Ser Thr Ser Met Asp Gly Val Phe Ala Ala Gly Asp Leu Val Asp275 280 285Arg Thr Tyr Arg Gln Ala Ile Thr Ala Ala Gly Ser Gly Cys Ala Ala290 295 300Ala Ile Asp Ala Glu Arg Trp Leu Ala Glu His Ala Gly Ser Lys Ala305 310 315 320Asn Glu Thr Thr Glu Glu Thr Gly Asp Val Asp Ser Thr Asp Thr Thr325 330 335Asp Trp Ser Thr Ala Met Thr Asp Ala Lys Asn Ala Gly Val Thr Ile340 345 350Glu Val Thr Asp Ala Ser Phe Phe Ala Asp Val Leu Ser Ser Asn Lys355 360 365Pro Val Leu Val Asp Phe Trp Ala Thr Trp Cys Gly Pro Cys Lys Met370 375 380Val Ala Pro Val Leu Glu Glu Ile Ala Ser Glu Gln Arg Asn Gln Leu385 390 395 400Thr Val Ala Lys Leu Asp Val Asp Thr Asn Pro Glu Met Ala Arg Glu405 410 415Phe Gln Val Val Ser Ile Pro Thr Met Ile Leu Phe Gln Gly Gly Gln420 425 430Pro Val Lys Arg Ile Val Gly Ala Lys Gly Lys Ala Ala Leu Leu Arg435 440 445Asp Leu Ser Asp Val Val Pro Asn Leu Asn450 45521052211178212PRT213鼠耳芥40052Met Pro Leu Ser Leu Arg Leu Ser Pro Ser Pro Thr Ala Leu Ser Pro1 5 10 15Thr Thr Gly Gly ghe Gly Pro Ser Arg Lys Gln Cys Arg Ile Pro Tyr20 25 30Ser Gly Val Pro Thr Thr Lys Ile Gly Phe Cys Ser Leu Asp Ser Arg35 40 45Lys Arg Gly Asp Ser Ser Val Val Arg Cys Ser Leu Glu Thr Val Asn50 55 60Val Ser Val Gly Gln Val Thr Glu Val Asp Lys Asp Thr Phe Trp Pro65 70 75 80Ile Val Lys Ala Ala Gly Glu Lys Leu Val Val Leu Asp Met Tyr Thr85 90 95Gln Trp Cys Gly Pro Cys Lys Val Ile Ala Pro Lys Tyr Lys Ala Leu100 105 110Ser Glu Lys Tyr Asp Asp Val Val Phe Leu Lys Leu Asp Cys Asn Pro115 120 125Asp Asn Arg Pro Leu Pro Lys Glu Leu Gly Ile Arg Val Val Pro Thr130 135 140Phe Lys Ile Leu Lys Asp Asn Lys Val Val Lys Glu Val Thr Gly Ala145 150 155 160Lys Tyr Asp Asp Leu Val Ala Ala Ile Glu Thr Ala Arg Ser Ala Ala165 170 175Ser Gly21053211185212PRT213鼠耳芥40053Met Pro Leu Ser Leu Arg Leu Ala Pro Ser Pro Thr Ser Phe Arg Tyr1 5 10 15Ser Pro Ile Thr Ser Thr Gly Ala Gly Gly Phe Ser Pro Val Lys Gln20 25 30His Cys Arg Ile Pro Asn Ser Gly Val Ala Thr Lys Ile Gly Phe Cys35 40 45Ser Gly Gly Gly Gly Val Leu Asp Ser Gly Arg Arg Ile Gly Ser Cys50 55 60Val Val Arg Cys Ser Leu Glu Thr Val Asn Val Thr Val Gly Gln Val65 70 75 80Thr Glu Val Asp Lys Asp Thr Phe Trp Pro Ile Val Lys Ala Ala Gly85 90 95Asp Lys Ile Val Val Leu Asp Met Tyr Thr Gln Trp Cys Gly Pro Cys100 105 110Lys Val Ile Ala Pro Lys Tyr Lys Glu Leu Ser Glu Lys Tyr Gln Asp115 120 125Met Val Phe Leu Lys Leu Asp Cys Asn Gln Asp Asn Lys Pro Leu Ala130 135 140Lys Glu Leu Gly Ile Arg Val Val Pro Thr Phe Lys Ile Leu Lys Asp145 150 155 160Asn Lys Val Val Lys Glu Val Thr Gly Ala Lys Tyr Glu Asp Leu Leu165 170 175Ala Ala Ile Glu Ala Ala Arg Ser Gly180 18521054211182212PRT213歐洲油菜(Brassica napus)40054Met Pro Leu Ser Leu Arg Leu Ala Pro Ser Pro Thr Ala Leu Ser Pro1 5 10 15Thr Thr Gly Gly Phe Ser Pro Ala Lys Lys Gln Cys Arg Ile Pro Ser20 25 30Tyr Ser Gly Val Ala Thr Thr Thr Arg Arg Ile Gly Leu Cys Ser Leu35 40 45Asp Tyr Val Lys Arg Gly Asp Ser Ser Val Val Arg Cys Ser Leu Gln50 55 60Thr Val Asn Val Ser Val Gly Gln Val Thr Glu Val Asp Lys Asp Thr65 70 75 80Phe Trp Pro Ile Val Lys Ala Ala Gly Glu Lys Ile Val Val Leu Asp85 90 95Met Tyr Thr Gln Trp Cys Gly Pro Cys Lys Val Ile Ala Pro Lys Tyr100 105 110Lys Ala Leu Ser Glu Lys Tyr Glu Asp Val Val Phe Leu Lys Leu Asp115 120 125Cys Asn Pro Glu Asn Arg Pro Leu Ala Lys Glu Leu Gly Ile Arg Val130 135 140Val Pro Thr Phe Lys Ile Leu Lys Asp Asn Gln Val Val Lys Glu Val145 150 155 160Thr Gly Ala Lys Tyr Asp Asp Leu Val Ala Ala Ile Glu Thr Ala Arg165 170 175Ser Ala Ser Ser Ser Gly18021055211191212PRT213Mesembryanthemum crystallinum40055Met Ala Met Gln Leu Ser Leu Ser His Gln Ser Trp Ala Lys Ser Leu1 5 10 15Ala Ser Pro Ile Thr Ser Phe Asp Pro Ala Arg Ser Pro Pro Lys Arg20 25 30Val Glu Leu Gly Pro Asn Cys Leu Asn Gly Gly Ala Thr Ala Gly Lys35 40 45Leu Met Arg Glu Lys Val Gly Glu Arg Met Arg Met Ser Gly Arg Ser50 55 60Cys Cys Val Lys Ala Ser Leu Glu Thr Ala Val Gly Ala Glu Ser Glu65 70 75 80Thr Leu Val Gly Lys Val Thr Glu Val Asp Lys Asp Thr Phe Trp Pro85 90 95Ile Ala Asn Gly Ala Gly Asp Lys Pro Val Val Leu Asp Met Tyr Thr100 105 110Gln Trp Cys Gly Pro Cys Lys Val Met Ala Pro Lys Tyr Gln Glu Leu115 120 125Ala Glu Lys Leu Leu Asp Val Val Phe Leu Lys Leu Asp Cys Asn Gln130 135 140Glu Asn Lys Pro Leu Ala Lys Glu Leu Gly Ile Arg Val Val Pro Thr145 150 155 160Phe Lys Ile Leu Lys Gly Gly Lys Ile Val Asp Glu Val Thr Gly Ala165 170 175Lys Phe Asp Lys Leu Val Ala Ala Ile Glu Ala Ala Arg Ser Ser180 185 19021056211182212PRT213豌豆(Pisum sativum)40056Met Ala Leu Asn Leu Cys Thr Ser Pro Lys Trp Ile Gly Thr Thr Val1 5 10 15Phe Asp Ser Ala Ser Ser Ser Lys Pro Ser Leu Ala Ser Ser Phe Ser20 25 30Thr Thr Ser Phe Ser Ser Ser Ile Leu Cys Ser Lys Arg Val Gly Leu35 40 45Gln Arg Leu Ser Leu Arg Arg Ser Ile Ser Val Ser Val Arg Ser Ser50 55 60Leu Glu Thr Ala Gly Pro Thr Val Thr Val Gly Lys Val Thr Glu Val65 70 75 80Asn Lys Asp Thr Phe Trp Pro Ile Val Asn Ala Ala Gly Asp Lys Thr85 90 95Val Val Leu Asp Met Phe Thr Lys Trp Cys Gly Pro Cys Lys Val Ile100 105 110Ala Pro Leu Tyr Glu Glu Leu Ser Gln Lys Tyr Leu Asp Val Val Phe115 120 125Leu Lys Leu Asp Cys Asn Gln Asp Asn Lys Ser Leu Ala Lys Glu Leu130 135 140Gly Ile Lys Val Val Pro Thr Phe Lys Ile Leu Lys Asp Asn Lys Ile145 150 155 160Val Lys Glu Val Thr Gly Ala Lys Phe Asp Asp Leu Val Ala Ala Ile165 170 175Asp Thr Val Arg Ser Ser18021057211190212PRT213菠菜(Spinacia oleracea)40057Met Ala Leu His Leu Ser Leu Ser His Gln Ser Trp Thr Ser Pro Ala1 5 10 15His Pro Ile Thr Ser Ser Asp Pro Thr Arg Ser Ser Val Pro Gly Thr20 25 30Gly Leu Ser Arg Arg Val Asp Phe Leu Gly Ser Cys Lys Ile Asn Gly35 40 45Val Phe Val Val Lys Arg Lys Asp Arg Arg Arg Met Arg Gly Gly Glu50 55 60Val Arg Ala Ser Met Glu Gln Ala Leu Gly Thr Gln Glu Met Glu Ala65 70 75 80Ile Val Gly Lys Val Thr Glu Val Asn Lys Asp Thr Phe Trp Pro Ile85 90 95Val Lys Ala Ala Gly Asp Lys Pro Val Val Leu Asp Met Phe Thr Gln100 105 110Trp Cys Gly Pro Cys Lys Ala Met Ala Pro Lys Tyr Glu Lys Leu Ala115 120 125Glu Glu Tyr Leu Asp Val Ile Phe Leu Lys Leu Asp Cys Asn Gln Glu130 135 140Asn Lys Thr Leu Ala Lys Glu Leu Gly Ile Arg Val Val Pro Thr Phe145 150 155 160Lys Ile Leu Lys Glu Asn Ser Val Val Gly Glu Val Thr Gly Ala Lys165 170 175Tyr Asp Lys Leu Leu Glu Ala Ile Gln Ala Ala Arg Ser Ser180 185 19021058211106212PRT213魚腥藻屬(Anabaena)40058Ser Ala Ala Ala Gln Val Thr Asp Ser Thr Phe Lys Gln Glu Val Leu15 10 15Asp Ser Asp Val Pro Val Leu Val Asp Phe Trp Ala Pro Trp Cys Gly20 25 30Pro Cys Arg Met Val Ala Pro Val Val Asp Glu Ile Ala Gln Gln Tyr35 40 45Glu Gly Lys Ile Lys Val Val Lys Val Asn Thr Asp Glu Asn Pro Gln50 55 60Val Ala Ser Gln Tyr Gly Ile Arg Ser Ile Pro Thr Leu Met Ile Phe65 70 75 80Lys Gly Gly Gln Lys Val Asp Met Val Val Gly Ala Val Pro Lys Thr85 90 95Thr Leu Ser Gln Thr Leu Glu Lys His Leu100 10521059211179212PRT213鼠耳芥40059Met Ala Ala Tyr Thr Cys Thr Ser Arg Pro Pro Ile Ser Ile Arg Ser1 5 10 15Glu Met Arg Ile Ala Ser Ser Pro Thr Gly Ser Phe Ser Thr Arg Gln20 25 30Met Phe Ser Val Leu Pro Glu Ser Ser Gly Leu Arg Thr Arg Val Ser35 40 45Leu Ser Ser Leu Ser Lys Asn Ser Arg Val Ser Arg Leu Arg Arg Gly50 55 60Val Ile Cys Glu Ala Gln Asp Thr Ala Thr Gly Ile Pro Val Val Asn65 70 75 80Asp Ser Thr Trp Asp Ser Leu Val Leu Lys Ala Asp Glu Pro Val Phe85 90 95Val Asp Phe Trp Ala Pro Trp Cys Gly Pro Cys Lys Met Ile Asp Pro100 105 110Ile Val Asn Glu Leu Ala Gln Lys Tyr Ala Gly Gln Phe Lys Phe Tyr115 120 125Lys Leu Asn Thr Asp Glu Ser Pro Ala Thr Pro Gly Gln Tyr Gly Val130 135 140Arg Ser Ile Pro Thr Ile Met Ile Phe Val Asn Gly Glu Lys Lys Asp145 150 155 160Thr Ile Ile Gly Ala Val Ser Lys Asp Thr Leu Ala Thr Ser Ile Asn165 170 175Lys Phe Leu21060211186212PRT213鼠耳芥40060Met Ala Ala Phe Thr Cys Thr Ser Arg Pro Pro Ile Ser Leu Arg Ser1 5 10 15Glu Thr Arg Ile Val Ser Ser Ser Pro Ser Ala Ser Ser Leu Ser Ser20 25 30Arg Arg Met Phe Ala Val Leu Pro Glu Ser Ser Gly Leu Arg Ile Arg35 40 45Leu Ser Leu Ser Pro Ala Ser Leu Thr Ser Ile His Gln Pro Arg Val50 55 60Ser Arg Leu Arg Arg Ala Val Val Cys Glu Ala Gln Glu Thr Thr Thr65 70 75 80Asp Ile Gln Val Val Asn Asp Ser Thr Trp Asp Ser Leu Val Leu Lys85 90 95Ala Thr Gly Pro Val Val Val Asp Phe Trp Ala Pro Trp Cys Gly Pro100 105 110Cys Lys Met Ile Asp Pro Leu Val Asn Asp Leu Ala Gln His Tyr Thr
115 120 125Gly Lys Ile Lys Phe Tyr Lys Leu Asn Thr Asp Glu Ser Pro Asn Thr130 135 140Pro Gly Gln Tyr Gly Val Arg Ser Ile Pro Thr Ile Met Ile Phe Val145 150 155 160Gly Gly Glu Lys Lys Asp Thr Ile Ile Gly Ala Val Pro Lys Thr Thr165 170 175Leu Thr Ser Ser Leu Asp Lys Phe Leu Pro180 18521061211173212PRT213鼠耳芥40061Met Ala Ile Ser Ser Ser Ser Ser Ser Ile Cys Phe Asn Pro Thr Arg1 5 10 15Phe His Thr Ala Arg His Ile Ser Ser Pro Ser Arg Leu Phe Pro Val20 25 30Thr Ser Phe Ser Pro Arg Ser Leu Arg Phe Ser Asp Arg Arg Ser Leu35 40 45Leu Ser Ser Ser Ala Ser Arg Leu Arg Leu Ser Pro Leu Cys Val Arg50 55 60Asp Ser Arg Ala Ala Glu Val Thr Gln Arg Ser Trp Glu Asp Ser Val65 70 75 80Leu Lys Ser Glu Thr Pro Val Leu Val Glu Phe Tyr Thr Ser Trp Cys85 90 95Gly Pro Cys Arg Met Val His Arg Ile Ile Asp Glu Ile Ala Gly Asp100 105 110Tyr Ala Gly Lys Leu Asn Cys Tyr Leu Leu Asn Ala Asp Asn Asp Leu115 120 125Pro Val Ala Glu Glu Tyr Glu Ile Lys Ala Val Pro Val Val Leu Leu130 135 140Phe Lys Asn Gly Glu Lys Arg Glu Ser Ile Met Gly Thr Met Pro Lys145 150 155 160Glu Phe Tyr Ile Ser Ala Ile Glu Arg Val Leu Asn Ser165 17021062211193212PRT213鼠耳芥40062Met Ala Ser Leu Leu Asp Ser Val Thr Val Thr Arg Val Phe Ser Leu1 5 10 15Pro Ile Ala Ala Ser Val Ser Ser Ser Ser Ala Ala Pro Ser Val Ser20 25 30Arg Arg Arg Ile Ser Pro Ala Arg Phe Leu Glu Phe Arg Gly Leu Lys35 40 45Ser Ser Arg Ser Leu Val Thr Gln Ser Ala Ser Leu Gly Ala Asn Arg50 55 60Arg Thr Arg Ile Ala Arg Gly Gly Arg Ile Ala Cys Glu Ala Gln Asp65 70 75 80Thr Thr Ala Ala Ala Val Glu Val Pro Asn Leu Ser Asp Ser Glu Trp85 90 95Gln Thr Lys Val Leu Glu Ser Asp Val Pro Val Leu Val Glu Phe Trp100 105 110Ala Pro Trp Cys Gly Pro Cys Arg Met Ile His Pro Ile Val Asp Gln115 120 125Leu Ala Lys Asp Phe Ala Gly Lys Phe Lys Phe Tyr Lys Ile Asn Thr130 135 140Asp Glu Ser Pro Asn Thr Pro Asn Arg Tyr Gly Ile Arg Ser Val Pro145 150 155 160Thr Val Ile Ile Phe Lys Gly Gly Glu Lys Lys Asp Ser Ile Ile Gly165 170 175Ala Val Pro Arg Glu Thr Leu Glu Lys Thr Ile Glu Arg Phe Leu Val180 185 190Glu21063211177212PRT213歐洲油菜40063Met Ala Ala Phe Thr Cys Thr Ser Ser Pro Pro Ile Ser Leu Arg Ser1 5 10 15Glu Met Met Ile Ala Ser Ser Lys Thr Val Ser Leu Ser Thr Arg Gln20 25 30Met Phe Ser Val Gly Gly Leu Arg Thr Arg Val Ser Leu Ser Ser Val35 40 45Ser Lys Asn Ser Arg Ala Ser Arg Leu Arg Arg Gly Gly Ile Ile Cys50 55 60Glu Ala Gln Asp Thr Ala Thr Gly Ile Pro Met Val Asn Asp Ser Thr65 70 75 80Trp Glu Ser Leu Val Leu Lys Ala Asp Glu Pro Val Val Val Asp Phe85 90 95Trp Ala Pro Trp Cys Gly Pro Cys Lys Met Ile Asp Pro Ile Val Asn100 105 110Glu Leu Ala Gln Gln Tyr Thr Gly Lys Ile Lys Phe Phe Lys Leu Ash115 120 125Thr Asp Asp Ser Pro Ala Thr Pro Gly Lys Tyr Gly Val Arg Ser Ile130 135 140Pro Thr Ile Met Ile Phe Val Lys Gly Glu Lys Lys Asp Thr Ile Ile145 150 155 160Gly Ala Val Pro Lys Thr Thr Leu Ala Thr Ser Ile Asp Lys Phe Leu165 170 175Gln21064211140212PRT213雷氏衣藻(Chlamydomonas reinhardtii)40064Met Ala Leu Val Ala Arg Arg Ala Ala Val Pro Ser Ala Arg Ser Ser15 10 15Ala Arg Pro Ala Phe Ala Arg Ala Ala Pro Arg Arg Ser Val Val Val20 25 30Arg Ala Glu Ala Gly Ala Val Asn Asp Asp Thr Phe Lys Asn Val Val35 40 45Leu Glu Ser Ser Val Pro Val Leu Val Asp Phe Trp Ala Pro Trp Cys50 55 60Gly Pro Cys Arg Ile Ile Ala Pro Val Val Asp Glu Ile Ala Gly Glu65 70 75 80Tyr Lys Asp Lys Leu Lys Cys Val Lys Leu Asn Thr Asp Glu Ser Pro85 90 95Asn Val Ala Ser Glu Tyr Gly Ile Arg Ser Ile Pro Thr Ile Met Val100 105 110Phe Lys Gly Gly Lys Lys Cys Glu Thr Ile Ile Gly Ala Val Pro Lys115 120 125Ala Thr Ile Val Gln Thr Val Glu Lys Tyr Leu Asn130 135 14021065211167212PRT213玉米(Zea mays)40065Met Ala Met Glu Thr Cys Phe Arg Ala Trp Ala Leu His Ala Pro Ala1 5 10 15Gly Ser Lys Asp Arg Leu Leu Val Gly Asn Leu Val Leu Pro Ser Lys20 25 30Arg Ala Leu Ala Pro Leu Ser Val Gly Arg Val Ala Thr Arg Arg Pro35 40 45Arg His Val Cys Gln Ser Lys Asn Ala Val Asp Glu Val Val Val Ala50 55 60Asp Glu Lys Asn Trp Asp Gly Leu Val Met Ala Cys Glu Thr Pro Val65 70 75 80Leu Val Glu Phe Trp Ala Pro Trp Cys Gly Pro Cys Arg Met Ile Ala85 90 95Pro Val Ile Asp Glu Leu Ala Lys Asp Tyr Ala Gly Lys Ile Thr Cys100 105 110Cys Lys Val Asn Thr Asp Asp Ser Pro Asn Val Ala Ser Thr Tyr Gly115 120 125Ile Arg Ser Ile Pro Thr Val Leu Ile Phe Lys Gly Gly Glu Lys Lys130 135 140Glu Ser Val Ile Gly Ala Val Pro Lys Ser Thr Leu Thr Thr Leu Ile145 150 155 160Asp Lys Tyr Ile Gly Ser Ser16521066211172212PRT213稻(Oryza sativa)40066Met Ala Leu Glu Thr Cys Phe Arg Ala Trp Ala Thr Leu His Ala Pro1 5 10 15Gln Pro Pro Ser Ser Gly Gly Ser Arg Asp Arg Leu Leu Leu Ser Gly20 25 30Ala Gly Ser Ser Gln Ser Lys Pro Arg Leu Ser Val Ala Ser Pro Ser35 40 45Pro Leu Arg Pro Ala Ser Arg Phe Ala Cys Gln Cys Ser Asn Val Val50 55 60Asp Glu Val Val Val Ala Asp Glu Lys Asn Trp Asp Ser Met Val Leu65 70 75 80Gly Ser Glu Ala Pro Val Leu Val Glu Phe Trp Ala Pro Trp Cys Gly85 90 95Pro Cys Arg Met Ile Ala Pro Val Ile Asp Glu Leu Ala Lys Glu Tyr100 105 110Val Gly Lys Ile Lys Cys Cys Lys Val Asn Thr Asp Asp Ser Pro Asn115 120 125Ile Ala Thr Asn Tyr Gly Ile Arg Ser Ile Pro Thr Val Leu Met Phe130 135 140Lys Asn Gly Glu Lys Lys Glu Ser Val Ile Gly Ala Val Pro Lys Thr145 150 155 160Thr Leu Ala Thr Ile Ile Asp Lys Tyr Val Ser Ser165 17021067211172212PRT213豌豆40067Met Ala Leu Glu Ser Leu Phe Lys Ser Ile His Thr Lys Thr Ser Leu1 5 10 15Ser Ser Ser Ile Val Phe Ile Phe Lys Gly Lys Ala Cys Leu Leu Thr20 25 30Ser Lys Ser ArgIle Gln Glu Ser Phe Ala Glu Leu Asn Ser Phe Thr35 40 45Ser Leu Val Leu Leu Ile Glu Asn His Val Leu Leu His Ala Arg Glu50 55 60Ala Val Asn Glu Val Gln Val Val Asn Asp Ser Ser Trp Asp Glu Leu65 70 75 80Val Ile Gly Ser Glu Thr Pro Val Leu Val Asp Phe Trp Ala Pro Trp85 90 95Cys Gly Pro Cys Arg Met Ile Ala Pro Ile Ile Asp Glu Leu Ala Lys100 105 110Glu Tyr Ala Gly Lys Ile Lys Cys Tyr Lys Leu Asn Thr Asp Glu Ser115 120 125Pro Asn Thr Ala Thr Lys Tyr Gly Ile Arg Ser Ile Pro Thr Val Leu130 135 140Phe Phe Lys Asn Gly Glu Arg Lys Asp Ser Val Ile Gly Ala Val Pro145 150 155 160Lys Ala Thr Leu Ser Glu Lys Val Glu Lys Tyr Ile165 17021068211181212PRT213菠菜40068Met Ala Ile Glu Asn Cys Leu Gln Leu Ser Thr Ser Ala Ser Val Gly1 5 10 15Thr Val Ala Val Lys Ser His Val His His Leu Gln Pro Ser Ser Lys20 25 30Val Asn Val Pro Thr Phe Arg Gly Leu Lys Arg Ser Phe Pro Ala Leu35 40 45Ser Ser Ser Val Ser Ser Ser Ser Pro Arg Gln Phe Arg Tyr Ser Ser50 55 60Val Val Cys Lys Ala Ser Glu Ala Val Lys Glu Val Gln Asp Val Asn65 70 75 80Asp Ser Ser Trp Lys Glu Phe Val Leu Glu Ser Glu Val Pro Val Met85 90 95Val Asp Phe Trp Ala Pro Trp Cys Gly Pro Cys Lys Leu Ile Ala Pro100 105 110Val Ile Asp Glu Leu Ala Lys Glu Tyr Ser Gly Lys Ile Ala Val Tyr115 120 125Lys Leu Asn Thr Asp Glu Ala Pro Gly Ile Ala Thr Gln Tyr Asn Ile130 135 140Arg Ser Ile Pro Thr Val Leu Phe Phe Lys Asn Gly Glu Arg Lys Glu145 150 155 160Ser Ile Ile Gly Ala Val Pro Lys Ser Thr Leu Thr Asp Ser Ile Glu165 170 175Lys Tyr Leu Ser Pro18021069211175212PRT213普通小麥(Triticum aestivum)40069Met Ala Leu Glu Thr Cys Leu Arg Gly Trp Ala Leu Tyr Ala Pro Gln1 5 10 15Ala Gly Ile Arg Glu Arg Leu Ser Ser Gly Ser Tyr Ala Pro Ser Arg20 25 30Pro Arg Thr Ala Ala Pro Ala Val Val Ser Pro Ser Pro Tyr Lys Ser35 40 45Ala Leu Val Ala Ala Arg Arg Pro Ser Arg Phe Val Cys Lys Cys Lys
50 55 60Asn Val Val Asp Glu Val Ile Val Ala Asp Glu Lys Asn Trp Asp Asn65 70 75 80Met Val Ile Ala Cys Glu Ser Pro Val Leu Val Glu Phe Trp Ala Pro85 90 95Trp Cys Gly Pro Cys Arg Met Ile Ala Pro Val Ile Asp Glu Leu Ala100 105 110Lys Asp Tyr Val Gly Lys Ile Lys Cys Cys Lys Val Asn Thr Asp Asp115 120 125Cys Pro Asn Ile Ala Ser Thr Tyr Gly Ile Arg Ser Ile Pro Thr Val130 135 140Leu Met Phe Lys Asp Gly Glu Lys Lys Glu Ser Val Ile Gly Ala Val145 150 155 160Pro Lys Thr Thr Leu Cys Thr Ile Ile Asp Lys Tyr Ile Gly Ser165 170 17521070211106212PRT213組囊藻(Anacystis nidulans)40070Ser Val Ala Ala Ala Val Thr Asp Ala Thr Phe Lys Gln Glu Val Leu1 5 10 15Glu Ser Ser Ile Pro Val Leu Val Asp Phe Trp Ala Pro Trp Cys Gly20 25 30Pro Cys Arg Met Val Ala Pro Val Val Asp Glu Ile Ala Gln Gln Tyr35 40 45Ser Asp Gln Val Lys Val Val Lys Val Asn Thr Asp Glu Asn Pro Ser50 55 60Val Ala Ser Gln Tyr Gly Ile Arg Ser Ile Pro Thr Leu Met Ile Phe65 70 75 80Lys Asp Gly Gln Arg Val Asp Thr Val Val Gly Ala Val Pro Lys Thr85 90 95Thr Leu Ala Asn Thr Leu Asp Lys His Leu100 10521071211107212PRT213Cyanidium caldarium40071Met Pro Ser Pro Ile Gln Val Thr Asp Phe Ser Phe Glu Lys Glu Val1 5 10 15Val Asn Ser Glu Lys Leu Val Leu Val Asp Phe TrpAla Pro Trp Cys20 25 30Gly Pro Cys Arg Met Ile Ser Pro Val Ile Asp Glu Leu Ala Gln Glu35 40 45Tyr Val Glu Gln Val Lys Ile Val Lys Ile Asn Thr Asp Glu Asn Pro50 55 60Ser Ile Ser Ala Glu Tyr Gly Ile Arg Ser Ile Pro Thr Leu Met Leu65 70 75 80Phe Lys Asp Gly Lys Arg Val Asp Thr Val Ile Gly Ala Val Pro Lys85 90 95Ser Thr Leu Thr Asn Ala Leu Lys Lys Tyr Leu100 10521072211102212PRT213Cyanidioschyzon merolae40072Met Leu His Ile Asp Glu Leu Thr Phe Glu Asn Glu Val Leu Gln Ser1 5 10 15Glu Lys Leu Val Leu Val Asp Phe Trp Ala Pro Trp Cys Gly Pro Cys20 25 30Arg Met Ile Gly Pro Ile Leu Glu Glu Ile Ala Lys Glu Phe Asn Leu35 40 45Lys Val Val Gln Val Asn Thr Asp Glu Asn Pro Asn Leu Ala Thr Phe50 55 60Tyr Gly Ile Arg Ser Ile Pro Thr Leu Met Leu Phe Lys Lys Gly Gln65 70 75 80Arg Val Asp Thr Val Ile Gly Ala Val Pro Lys Ser Ile Leu Ile His85 90 95Thr Ile Asn Lys Tyr Leu10021073211109212PRT213Griffithsia pacifica40073Met Ser Ile Ser Gln Val Ile Asp Thr Ser Phe His Glu Glu Val Ile1 5 10 15Asn Ser Arg Gln Pro Val Leu Val Asp Phe Trp Ala Pro Trp Cys Gly20 25 30Pro Cys Arg Met Ile Ala Ser Thr Ile Asp Glu Ile Ala His Asp Tyr35 40 45Lys Asp Lys Leu Lys Val Val Lys Val Asn Thr Asp Gln Asn Pro Thr50 55 60Ile Ala Thr Glu Tyr Gly Ile Arg Ser Ile Pro Thr Val Met Ile Phe65 70 75 80Ile Asn Gly Lys Lys Val Asp Thr Val Val Gly Ala Val Pro Lys Leu85 90 95Thr Leu Leu Asn Thr Leu Gln Lys His Leu Lys Ser Thr100 10521074211107212PRT213條斑紫菜(Porphyra yezoensis)40074Met Ser Val Ser Gln Val Thr Asp Ala Ser Phe Lys Gln Glu Val Ile1 5 10 15Asn Asn Asn Leu Pro Val Leu Val Asp Phe Trp Ala Pro Trp Cys Gly20 25 30Pro Cys Arg Met Val Ser Pro Val Val Asp Glu Ile Ala Glu Glu Tyr35 40 45Glu Ser Ser Ile Lys Val Val Lys Ile Asn Thr Asp Asp Asn Pro Thr50 55 60Ile Ala Ala Glu Tyr Gly Ile Arg Ser Ile Pro Thr Leu Met Ile Phe65 70 75 80Lys Ala Gly Glu Arg Val Asp Thr Val Ile Gly Ala Val Pro Lys Ser85 90 95Thr Leu Ala Ser Thr Leu Asn Lys Tyr Ile Ser100 10521075211107212PRT213Porphyra purpurea40075Met Ser Val Ser Gln Val Thr Asp Ala Ser Phe Lys Gln Glu Val Ile1 5 10 15Asn Asn Asp Leu Pro Val Leu Val Asp Phe Trp Ala Pro Trp Cys Gly20 25 30Pro Cys Arg Met Val Ser Pro Val Val Asp Ala Ile Ala Glu Glu Tyr35 40 45Glu Ser Ser Ile Lys Val Val Lys Ile Asn Thr Asp Asp Asn Pro Thr50 55 60Ile Ala Ala Glu Tyr Gly Ile Arg Ser Ile Pro Thr Leu Met Ile Phe65 70 75 80Lys Ser Gly Glu Arg Val Asp Thr Val Ile Gly Ala Val Pro Lys Ser85 90 95Thr Leu Glu Ser Thr Leu Asn Lys Tyr Ile Ser100 10521076211114212PRT213鼠耳芥40076Met Ala Ser Glu Glu Gly Gln Val Ile Ala Cys His Thr Val Glu Thr1 5 10 15Trp Asn Glu Gln Leu Gln Lys Ala Asn Glu Ser Lys Thr Leu Val Val20 25 30Val Asp Phe Thr Ala Ser Trp Cys Gly Pro Cys Arg Phe Ile Ala Pro35 40 45Phe Phe Ala Asp Leu Ala Lys Lys Leu Pro Asn Val Leu Phe Leu Lys50 55 60Val Asp Thr Asp Glu Leu Lys Ser Val Ala Ser Asp Trp Ala Ile Gln65 70 75 80Ala Met Pro Thr Phe Met Phe Leu Lys Glu Gly Lys Ile Leu Asp Lys85 90 95Val Val Gly Ala Lys Lys Asp Glu Leu Gln Ser Thr Ile Ala Lys His100 105 110Leu Ala21077211110212PRT213魚腥藻屬40077Ser Lys Gly Val Ile Thr Ile Thr Asp Ala Glu Phe Glu Ser Glu Val1 5 10 15Leu Lys Ala Glu Gln Pro Val Leu Val Tyr Phe Trp Ala Ser Trp Cys20 25 30Gly Pro Cys Gln Leu Met Ser Pro Leu Ile Asn Leu Ala Ala Asn Thr35 40 45Tyr Ser Asp Arg Leu Lys Val Val Lys Leu Glu Ile Asp Pro Asn Pro50 55 60Thr Thr Val Lys Lys Tyr Lys Val Glu Gly Val Pro Ala Leu Arg Leu65 70 75 80Val Lys Gly Glu Gln Ile Leu Asp Ser Thr Glu Gly Val Ile Ser Lys85 90 95Asp Lys Leu Leu Ser Phe Leu Asp Thr His Leu Asn Asn Asn100 105 11021078211123212PRT213歐洲油萊40078Met Ala Ala Thr Ala Glu Val Ile Pro Ala Gly Glu Val Ile Ala Cys1 5 10 15His Thr Val Glu Asp Trp Asn Asn Lys Leu Lys Ala Ala Lys Glu Ser20 25 30Asn Lys Leu Ile Val Ile Asp Phe Thr Ala Val Trp Cys Pro Pro Cys35 40 45Arg Phe Ile Ala Pro Ile Phe Val Glu Leu Ala Lys Lys His Leu Asp50 55 60Val Val Phe Phe Lys Val Asp Val Asp Glu Leu Ala Thr Val Ala Gln65 70 75 80Glu Phe Asp Val Gln Ala Met Pro Thr Phe Val Tyr Met Lys Gly Glu85 90 95Glu Lys Leu Asp Lys Val Val Gly Ala Ala Lys Glu Glu Ile Glu Ala100 105 110Lys Leu Leu Lys His Ser Gln Val Ala Ala Ala11512021079211126212PRT213菸草40079Met Ala Ala Asn Asp Ala Thr Ser Ser Glu Glu Gly Gln Val Phe Gly1 5 10 15Cys His Lys Val Glu Glu Trp Asn Glu Tyr Phe Lys Lys Gly Val Glu20 25 30Thr Lys Lys Leu Val Val Val Asp Phe Thr Ala Ser Trp Cys Gly Pro35 40 45Cys Arg Phe Ile Ala Pro Ile Leu Ala Asp Ile Ala Lys Lys Met Pro50 55 60His Val Ile Phe Leu Lys Val Asp Val Asp Glu Leu Lys Thr Val Ser65 70 75 80Ala Glu Trp Ser Val Glu Ala Met Pro Thr Phe Val Phe Ile Lys Asp85 90 95Gly Lys Glu Val Asp Arg Val Val Gly Ala Lys Lys Glu Glu Leu Gln100 105 110Gln Thr Ile Val Lys His Ala Ala Pro Ala Thr Val Thr Ala115 120 12521080211133212PRT213鼠耳芥40080Met Gly Gly Ala Leu Ser Thr Val Phe Gly Ser Gly Glu Asp Ala Thr1 5 10 15Ala Ala Gly Thr Glu Ser Glu Pro Ser Arg Val Leu Lys Phe Ser Ser20 25 30Ser Ala Arg Trp Gln Leu His Phe Asn Glu Ile Lys Glu Ger Asn Lys35 40 45Leu Leu Val Val Asp Phe Ser Ala Ser Trp Cys Gly Pro Cys Arg Met50 55 60Ile Glu Pro Ala Ile His Ala Met Ala Asp Lys Phe Asn Asp Val Asp65 70 75 80Phe Val LysLeu Asp Val Asp Glu Leu Pro Asp Val Ala Lys Glu Phe85 90 95Asn Val Thr Ala Met Pro Thr Phe Val Leu Val Lys Arg Gly Lys Glu100 105 110Ile Glu Arg Ile Ile Gly Ala Lys Lys Asp Glu Leu Glu Lys Lys Val115 120 125Ser Lys Leu Arg Ala13021081211119212PRT213歐洲油菜40081Met Ala Ala Glu Glu Gly Gln Val Ile Gly Cys His Glu Ile Asp Val1 5 10 15Trp Ala Val Gln Leu Asp Thr Ala Lys Gln Ser Ash Lys Leu Ile Val20 25 30Ile Asp Phe Thr Ala Ser Trp Cys Pro Pro Cys Arg Met Ile Ala Pro35 40 45Val Phe Ala Asp Leu Ala Lys Lys Phe Met Ser Ser Ala Ile Phe Phe50 55 60Lys Val Asp Val Asp Glu Leu Gln Asn Val Ala Gln Glu Phe Gly Val65 70 75 80Glu Ala Met Pro Thr Phe Val Leu Ile Lys Asp Gly Asn Val Val Asp85 90 95Lys Val Val Gly Ala Arg Lys Glu Asp Leu His Ala Thr Ile Ala Lys100 105 110His Thr Gly Val Ala Thr Ala11521082211118212PRT213菸草40082Met Ala Glu Glu Gly Gln Val Ile Gly Val His Thr Val Asp Ala Trp1 5 10 15Asn Glu His Leu Gln Lys Gly Ile Asp Asp Lys Lys Leu Ile Val Val20 25 30Asp Phe Thr Ala Ser Trp Cys Gly Pro Cys Lys Phe Ile Ala Ser Phe35 40 45Tyr Ala Glu Leu Ala Lys Lys Met Pro Thr Val Thr Phe Leu Lys Val50 55 60Asp Val Asp Glu Leu Lys Ser Val Ala Thr Asp Trp Ala Val Glu Ala65 70 75 80Met Pro Thr Phe Met Phe Leu Lys Glu Gly Lys Ile Val Asp Lys Val85 90 95Val Gly Ala Lys Lys Asp Glu Leu Gln Gln Thr Ile Ala Lys His Ile100 105 110Ser Ser Thr Ser Thr Ala11521083211118212PRT213鼠耳芥40083Met Ala Ala Glu Gly Glu Val Ile Ala Cys His Thr Val Glu Asp Trp1 5 10 15Thr Glu Lys Leu Lys Ala Ala Asn Glu Ser Lys Lys Leu Ile Val Ile20 25 30Asp Phe Thr Ala Thr Trp Cys Pro Pro Cys Arg Phe Ile Ala Pro Val35 40 45Phe Ala Asp Leu Ala Lys Lys His Leu Asp Val Val Phe Phe Lys Val50 55 60Asp Val Asp Glu Leu Asn Thr Val Ala Glu Glu Phe Lys Val Gln Ala65 70 75 80Met Pro Thr Phe Ile Phe Met Lys Glu Gly Glu Ile Lys Glu Thr Val85 90 95Val Gly Ala Ala Lys Glu Glu Ile Ile Ala Asn Leu Glu Lys His Lys
100 105 110Thr Val Val Ala Ala Ala11521084211125212PRT213鼠耳芥 iana40084Met Ala Ala Glu Glu Gly Gln Val Ile Gly Cys His Thr Asn Asp Val1 5 10 15Trp Thr Val Gln Leu Asp Lys Ala Lys Glu Ser Asn Lys Leu Ile Val20 25 30Ile Asp Phe Thr Ala Ser Trp Cys Pro Pro Cys Arg Met Ile Ala Pro35 40 45Ile Phe Asn Asp Leu Ala Lys Lys Phe Met Ser Ser Ala Ile Phe Phe50 55 60Lys Val Asp Val Asp Glu Leu Gln Ser Val Ala Lys Glu Phe Gly Val65 70 75 80Glu Ala Met Pro Thr Phe Val Phe Ile Lys Ala Gly Glu Val Val Asp85 90 95Lys Leu Val Gly Ala Asn Lys Glu Asp Leu Gln Ala Lys Ile Val Lys100 105 110His Thr Gly Val Thr Thr Val Val Asn Gln Phe Glu Ala115 120 12521085211118212PRT213鼠耳芥40085Met Ala Gly Glu Gly Glu Val Ile Ala Cys His Thr Leu Glu Val Trp1 5 10 15Asn Glu Lys Val Lys Asp Ala Asn Glu Ser Lys Lys Leu Ile Val Ile20 25 30Asp Phe Thr Ala Ser Trp Cys Pro Pro Cys Arg Phe Ile Ala Pro Val35 40 45Phe Ala Glu Met Ala Lys Lys Phe Thr Asn Val Val Phe Phe Lys Ile50 55 60Asp Val Asp Glu Leu Gln Ala Val Ala Gln Glu Phe Lys Val Glu Ala65 70 75 80Met Pro Thr Phe Val Phe Met Lys Glu Gly Asn Ile Ile Asp Arg Val85 90 95Val Gly Ala Ala Lys Asp Glu Ile Asn Glu Lys Leu Met Lys His Gly100 105 110Gly Leu Val Ala Ser Ala11521086211123212PRT213蕪菁40086Met Ala Ala Thr Ala Glu Leu Ile Pro Ala Gly Glu Val Ile Ala Cys1 5 10 15His Thr Val Glu Asp Trp Asn Asn Lys Leu Lys Ala Ala Lys Glu Ser20 25 30Asn Lys Leu Ile Val Ile Asp Phe Thr Ala Val Trp Cys Pro Pro Cys35 40 45Arg Phe Ile Ala Pro Ile Phe Val Glu Leu Ala Lys Lys His Leu Asp50 55 60Val Val Phe Phe Lys Val Asp Val Asp Glu Leu Ala Thr Val Ala Lys65 70 75 80Glu Phe Asp Val Gln Ala Met Pro Thr Phe Val Tyr Met Lys Gly Glu85 90 95Glu Lys Leu Asp Lys Val Val Gly Ala Ala Lys Glu Glu Ile Glu Ala100 105 110Lys Leu Leu Lys His Ser Gln Val Ala Ala Ala115 12021087211112212PRT213雷氏衣藻40087Gly Gly Ser Val Ile Val Ile Asp Ser Lys Ala Ala Trp Asp Ala Gln1 5 10 15Leu Ala Lys Gly Lys Glu Glu His Lys Pro Ile Val Val Asp Phe Thr20 25 30Ala Thr Trp Cys Gly Pro Cys Lys Met Ile Ala Pro Leu Phe Glu Thr35 40 45Leu Ser Asn Asp Tyr Ala Gly Lys Val Ile Phe Leu Lys Val Asp Val50 55 60Asp Ala Val Ala Ala Val Ala Glu Ala Ala Gly Ile Thr Ala Met Pro65 70 75 80Thr Phe His Val Tyr Lys Asp Gly Val Lys Ala Asp Asp Leu Val Gly85 90 95Ala Ser Gln Asp Lys Leu Lys Ala Leu Val Ala Lys His Ala Ala Als100 105 11021088211116212PRT213蕎麥(Fagopyrum esculentum)40088Met Ala Glu Glu Ala Gln Val Ile Ala Cys His Thr Val Gln Glu Trp1 5 10 15Asn Glu Lys Phe Gln Lys Ala Lys Asp Ser Gly Lys Leu Ile Val Ile20 25 30Asp Phe Thr Ala Ser Trp Cys Gly Pro Cys Arg Val Ile Thr Pro Tyr35 40 45Val Ser Glu Leu Ala Lys Lys Phe Pro His Val Ala Phe Phe Lys Val50 55 60Asp Val Asp Asp Leu Lys Asp Val Ala Glu Glu Tyr Lys Val Glu Ala65 70 75 80Met Pro Ser Phe Val Ile Leu Lys Glu Gly Gln Glu Val Glu Arg Ile85 90 95Val Gly Ala Arg Lys Asp Glu Leu Leu His Lys Ile Ala Val His Ala100 105 110Pro Ile Thr Ala11521089211122212PRT213稻40089Met Ala Ala Glu Glu Gly Val Val Ile Ala Cys His Asn Lys Asp Glu1 5 10 15Phe Asp Ala Gln Met Thr Lys Ala Lys Glu Ala Gly Lys Val Val Ile20 25 30Ile Asp Phe Thr Ala Ser Trp Cys Gly Pro Cys Arg Phe Ile Ala Pro
35 40 45Val Phe Ala Glu Tyr Ala Lys Lys Phe Pro Gly Ala Val Phe Leu Lys50 55 60Val Asp Val Asp Glu Leu Lys Glu Val Ala Glu Lys Tyr Asn Val Glu65 70 75 80Ala Met Pro Thr Phe Leu Phe Ile Lys Asp Gly Ala Glu Ala Asp Lys85 90 95Val Val Gly Ala Arg Lys Asp Asp Leu Gln Asn Thr Ile Val Lys His100 105 110Val Gly Ala Thr Ala Ala Ser Ala Ser Ala115 12021090211125212PRT213黑雲杉(Picea mariana)40090Met Ala Glu Gly Asn Val Phe Ala Cys His Ser Thr Glu Gly Trp Arg1 5 10 15Ser Lys Leu Gln Glu Ala Ile Asp Thr Lys Arg Leu Val Ala Val Asp20 25 30Phe Thr Ala Thr Trp Cys Gly Pro Cys Arg Val Ile Gly Pro Val Phe35 40 45Val Glu Leu Ser Lys Lys Phe Pro Glu Ile Phe Phe Leu Lys Val Asp50 55 60Val Asp Glu Leu Arg Asp Val Ala Gln Glu Trp Asp Val Glu Ala Met65 70 75 80Pro Thr Phe Ile phe Ile Lys Asp Gly Lys Ala Val Asp Lys Val Val85 90 95Gly Ala Lys Lys Asp Asp Leu Glu Arg Lys Val Ala Ala Leu Ala Ala100 105 110Ala Ala Thr Thr Thr Glu Ala Thr Leu Pro Ala Gln Ala115 120 12521091211118212PRT213蓖麻(Ricinus communis)40091Met Ala Ala Glu Glu Gly Gln Val Ile Gly Cys His Thr Val Glu Ala1 5 10 15Trp Asn Glu Gln Leu Gln Lys Gly Asn Asp Thr Lys Gly Leu Ile Val20 25 30Val Asp Phe Thr Ala Ser Trp Cys Gly Pro Cys Arg Phe Ile Ala Pro35 40 45Phe Leu Ala Glu Leu Ala Lys Lys Leu Pro Asn Val Thr Phe Leu Lys50 55 60Val Asp Val Asp Glu Leu Lys Thr Val Ala His Glu Trp Ala Val Glu65 70 75 80Ser Met Pro Thr Phe Met Phe Leu Lys Glu Gly Lys Ile Met Asp Lys85 90 95Val Val Gly Ala Lys Lys Asp Glu Leu Gln Gln Thr Ile Ala Lys His100 105 110Met Ala Thr Ala Ser Thr11521092211126212PRT213普通小麥40092Ala Ala Ser Ala Ala Thr Ala Thr Ala Thr Ala Ala Ala Val Gly Ala1 5 10 15Gly Glu Val Ile Ser Val His Ser Leu Glu Gln Trp Thr Met Gln Ile20 25 30Glu Glu Ala Asn Ala Ala Lys Lys Leu Val Val Ile Asp Phe Thr Ala35 40 45Ser Trp Cys Gly Pro Cys Arg Ile Met Ala Pro Ile Phe Ala Asp Leu50 55 60Ala Lys Lys Phe Pro Ala Ala Val Phe Leu Lys Val Asp Val Asp Glu65 70 75 80Leu Lys Pro Ile Ala Glu Gln Phe Ser Val Glu Ala Met Pro Thr phe85 90 95Leu phe Met Lys Glu Gly Asp Val Lys Asp Arg Val Val Gly Ala Ile100 105 110Lys Glu Glu Leu Thr Thr Lys Val Gly Leu His Ala Ala Gln115 120 12521093211109212PRT213構巢麴黴40093Gly Ala Ser Glu His Val Pro Pro Ile Thr Ser Lys Ala Glu Phe Gln1 5 10 15Glu Lys Val Leu Asn Ala Lys Gly Phe Val Val Val Asp Cys Phe Ala20 25 30Thr Trp Cys Gly Pro Cys Lys Ala Ile Ala Pro Thr Val Glu Lys Phe35 40 45Ala Gln Thr Tyr Thr Asp Ala Ser Phe Tyr Gln Ile Asp Val Asp Glu50 55 60Leu Ser Glu Val Ala Ala Glu Leu Gly Ile Arg Ala Met Pro Thr Phe65 70 75 80Leu Leu Phe Lys Asp Gly Gln Lys Val Ser Asp Val Val Gly Ala Asn85 90 95Pro Gly Ala Leu Glu Ala Gly Ile Lys Ala Leu Leu Ala100 10521094211105212PRT213脂環酸桿菌屬40094Ala Thr Met Thr Leu Thr Asp Ala Asn Phe Gln Gln Ala Ile Gln Gly1 5 10 15Asp Lys Pro Val Leu Val Asp Phe Trp Ala Ala Trp Cys Gly Pro Cys20 25 30Arg Met Met Ala Pro Val Leu Glu Glu Phe Ala Glu Ala His Ala Asp35 40 45Lys Val Thr Val Ala Lys Leu Asn Val Asp Glu Asn Pro Glu Thr Thr50 55 60Ser Gln Phe Gly Ile Met Ser Ile Pro Thr Leu Ile Leu Phe Lys Gly65 70 75 80Gly Arg Pro Val Lys Gln Leu Ile Gly Tyr Gln Pro Lys Glu Gln Leu85 90 95Glu Ala Gln Leu Ala Asp Val Leu Gln100 1052109521191212PRT213閃爍古生球菌40095Met Val Met Met Lys Leu Phe Thr Ser Pro Thr Cys Pro Tyr Cys Pro1 5 10 15Lys Ala Glu Lys Val Val Ser Lys Val Ala Lys Glu Glu Gly Val Leu20 25 30Ala Ile Asn Leu Pro Val Asn Thr Asp Glu Gly Leu Lys Glu Ala Leu35 40 45Lys Phe Gly Ile Arg Gly Val Pro Ala Leu Val Ile Asn Asp Lys Tyr50 55 60Leu Ile Leu Gly Val Pro Asp Glu Gly Glu Leu Arg Gln Leu Ile Arg65 70 75 80Lys Leu Lys Gly Gly Glu Glu Tyr Gly Ala Ser85 9021096211103212PRT213枯草芽孢桿菌(Bacillus subtilis)40096Ala Ile Val Lys Ala Thr Asp Gln Ser Phe Ser Ala Glu Thr Ser Glu1 5 10 15Gly Val Val Leu Ala Asp Phe Trp Ala Pro Trp Cys Gly Pro Cys uys20 25 30Met Ile Ala Pro Val Leu Glu Glu Leu Asp Gln Glu Met Gly Asp Lys35 40 45Leu Lys Ile Val Lys Ile Asp Val Asp Glu Asn Gln Glu Thr Ala Gly50 55 60Lys Tyr Gly Val Met Ser Ile Pro Thr Leu Leu Val Leu Lys Asp Gly65 70 75 80Glu Val Val Glu Thr Ser Val Gly Phe Lys Pro Lys Glu Ala Leu Gln85 90 95Glu Leu Val Asn Lys His Leu1002109721187212PRT213噬菌體T440097Met Phe Lys Val Tyr Gly Tyr Asp Ser Asn Ile His Lys Cys Val Tyr1 5 10 15Cys Asp Asn Ala Lys Arg Leu Leu Thr Val Lys Lys Gln Pro Phe Glu20 25 30Phe Ile Asn Ile Met Pro Glu Lys Gly Val Phe Asp Asp Glu Lys Ile35 40 45Ala Glu Leu Leu Thr Lys Leu Gly Arg Asp Thr Gln Ile Gly Leu Thr50 55 60Met Pro Gln Val Phe Ala Pro Asp Gly Ser His Ile Gly Gly Phe Asp65 70 75 80Gln Leu Arg Glu Tyr Phe Lys8521098211117212PRT213布氏疏螺旋體(Borrelia burgdorferi)40098Met Ala Ile Ser Leu Thr Glu Glu Asp Phe Val Val Lys Val Phe Asp1 5 10 15Tyr Lys Asn Asp Lys Glu Trp Ser Phe Arg Gly Asp Arg Pro Ala Ile20 25 30Ile Asp Phe Tyr Ala Asn Trp Cys Gly pro Cys Lys Met Leu Ser Pro35 40 45Ile Phe Glu Lys Leu Ser Lys Lys Tyr Glu Asn Ser Ile Asp Phe Tyr50 55 60Lys Val Asp Thr Asp Lys Glu Gln Asp Ile Ser Ser Ala Ile Gly Val65 70 75 80Gln Ser Leu Pro Thr Ile Leu Phe Ile Pro Val Asp Gly Lys Pro Lys85 90 95Val Ser Val Gly Phe Leu Gln Glu Asp Ala Phe Glu Asn Ile Ile Lys100 105 110Asp Phe Phe Gly Phe11521099211108212PRT213蚜蟲巴克納氏菌(Buchnera aphidicola)40099Met Asn Lys Ile Ile Glu Leu Thr Asp Gln Asn Phe Glu Glu Gln Val1 5 10 15Leu Asn Ser Lys Ser Phe Phe Leu Val Asp Phe Trp Ala Gln Trp Cys20 25 30Asn Pro Cys Lys Ile Leu Ala Pro Ile Leu Glu Glu Ile Ser Lys Glu35 40 45Tyr Ser Asn Lys Val Ile Val Gly Lys Leu Asn Ile Glu Glu Asn Pro50 55 60Asn Thr Ala Pro Val Tyr Ser Ile Arg Ser Ile Pro Thr Leu Leu Leu65 70 75 80Phe Asn Asn Ser Glu Val Leu Ala Thr Lys Val Gly Ala Val Ser Lys85 90 95Leu Glu Leu Lys Glu Phe Leu Asp Glu Asn Ile Asn100 105210100211108212PRT213蚜蟲巴克納氏菌400100Met Asn Lys Ile Ile Glu Leu Thr Asp Gln Asn Phe Glu Lys Glu Val1 5 10 15Leu Glu His Lys Ser Phe Val Leu Val Asp Phe Trp Ala Glu Trp Cys20 25 30Asn Pro Cys Lys Ile Leu Ala Pro Ile Leu Glu Glu Ile Ala Gln Glu35 40 45Tyr Phe Asn Lys Ile Lys Val Gly Lys Leu Asn Ile Glu Lys Asn Pro50 55 60Asn Thr Ala Pro Ile Tyr Ser Ile Arg Gly Ile Pro Ala Leu Leu Leu65 70 75 80Phe His Gly Arg Glu Val Leu Ala Thr Lys Val Gly Ala Ile Ser Lys85 90 95Leu Gln Leu Lys Asp Phe Leu Asp Glu Asn Ile Lys100 105210101211108212PRT213泥生綠菌220221VARIANT22216，17，38，42，45，54，55，58，66，72，75，79，80，81，94，99，103223Xaa＝任何胺基酸400101Ala Gly Lys Tyr Phe Glu Ala Thr Asp Lys Asn Phe Gln Thr Glu Xaa1 5 10 15Xaa Asp Ser Asp Lys Ala Val Leu Val Asp Phe Trp Ala Ser Trp Cys20 25 30Gly Pro Cys Met Met Xaa Gly Pro Val Xaa Glu Gln Xaa Ala Asp Asp35 40 45Tyr Glu Gly Lys Ala Xaa Xaa Ala Lys Xaa Asn Val Asp Glu Asn Pro50 55 60Asn Xaa Ala Gly Gln Tyr Gly Xaa Arg Ser Xaa Pro Thr Met Xaa Xaa65 70 75 80Xaa Lys Gly Gly Lys Val Val Asp Gln Met Val Gly Ala Xaa Pro Lys85 90 95Asn Met Xaa Ala Lys Lys Xaa Asp Glu His Ile Gly100 105210102211102212PRT213Chlamydia muridarum400102Met Val Gln Ile Val Ser Gln Asp Asn Phe Ala Asp Ser Ile Ala Ser1 5 10 15Gly Leu Val Leu Val Asp Phe Phe Ala Glu Trp Cys Gly Pro Cys Lys20 25 30Met Leu Thr Pro Val Leu Glu Ala Leu Ala Ala Glu Leu Pro Tyr Val35 40 45Thr Ile Leu Lys Leu Asp Ile Asp Ala Ser Pro Arg Pro Ala Glu Gln50 55 60Phe Gly Val Ser Ser Ile Pro Thr Leu Ile Leu Phe Lys Asp Gly Lys65 70 75 80Glu Val Glu Arg Ser Val Gly Leu Lys Asp Lys Asp Ser Leu Val Lys85 90 95Leu Ile Ser Lys His Gln100210103211102212PRT213肺炎衣原體400103Met Val Lys Ile Ile Ser Ser Glu Asn Phe Asp Ser Phe Ile Ala Ser1 5 10 15Gly Leu Val Leu Val Asp Phe Phe Ala Glu Trp Cys Gly Pro Cys Arg20 25 30Met Leu Thr Pro Ile Leu Glu Asn Leu Ala Ala Glu Leu Pro His Val35 40 45Thr Ile Gly Lys Ile Asn Ile Asp Glu Asn Ser Lys Pro Ala Glu Thr50 55 60Tyr Glu Val Ser Ser Ile Pro Thr Leu Ile Leu Phe Lys Asp Gly Asn65 70 75 80Glu Val Ala Arg Val Val Gly Leu Lys Asp Lys Glu Phe Leu Thr Asn85 90 95Leu Ile Asn Lys His Ala100210104211102212PRT213鸚鵡熱衣原體(Psittaci)400104Met Val Lys Val Val Ser Ala Glu Asn Phe Asn Ser Phe Ile Ala Thr1 5 10 15Gly Leu Val Leu Ile Asp Phe Phe Ala Glu Trp Cys Gly Pro Cys Lys20 25 30Met Leu Thr Pro Val Leu Glu Ser Leu Glu Ala Glu Val Ser Ser Val35 40 45Leu Ile Gly Lys Val Asn Ile Asp Asp His Pro Ala Pro Ala Glu Gln50 55 60Tyr Gly Val Ser Ser Ile Pro Thr Leu Ile Leu Phe Lys Asp Gly Lys65 70 75 80Glu Val Asp Arg Val Val Gly Leu Lys Asp Lys Asp Ser Leu Ile Arg85 90 95Leu Ile Asn Gln His Ser100210105211102212PRT213砂眼衣原體400105Met Val Gln Val Val Ser Gln Glu Asn Phe Ala Asp Ser Ile Ala Ser1 5 10 15Gly Leu Val Leu Ile Asp Phe Phe Ala Glu Trp Cys Gly Pro Cys Lys20 25 30Met Leu Thr Pro Val Leu Glu Ala Leu Ala Ala Glu Leu Pro His Val35 40 45Thr Ile Leu Lys Val Asp Ile Asp Ser Ser Pro Arg Pro Ala Glu Gln50 55 60Tyr Ser Val Ser Ser Ile Pro Thr Leu Ile Leu Phe Lys Asp Gly Lys65 70 75 80Glu Val Glu Arg Ser Val Gly Lau Lys Asp Lys Asp Ser Leu Ile Lys85 90 95Leu Ile Ser Lys His Gln100210106211105212PRT213腎棒桿菌400106Ala Thr Val Lys Val Asp Asn Ser Asn Phe Gln Ser Asp Val Leu Gln1 5 10 15Ser Ser Glu Pro Val Val Val Asp Phe Trp Ala Glu Trp Cys Gly Pro20 25 30Cys Lys Met Ile Ala Pro Ala Leu Asp Glu Ile Ala Thr Glu Met Ala35 40 45Gly Gln Val Lys Ile Ala Lys Val Asn Ile Asp Glu Asn Pro Glu Leu50 55 60Ala Ala Gln Phe Gly Val Arg Ser Ile Pro Thr Leu Leu Met Phe Lys65 70 75 80Asp Gly Glu Leu Ala Ala Asn Met Val Gly Ala Ala Pro Lys Ser Arg85 90 95Leu Ala Asp Trp Ile Lys Ala Ser Ala100105210107211107212PRT213腎棒桿菌400107Ser Ala Thr Ile Val Asn Thr Thr Asp Glu Asn Phe Gln Ala Asp Val1 5 10 15Leu Asp Ala Glu Thr Pro Val Leu Val Asp Phe Trp Ala Gly Trp Cys20 25 30Ala Pro Cys Lys Ala Ile Ala Pro Val Leu Glu Glu Leu Ser Asn Glu35 40 45Tyr Ala Gly Lys Val Lys Ile Val Lys Val Asp Val Thr Ser Cys Glu50 55 60Asp Thr Ala Val Lys Tyr Asn Ile Arg Asn Ile Pro Ala Leu Leu Met65 70 75 80Phe Lys Asp Gly Glu Val Val Ala Gln Gln Val Gly Ala Ala Pro Arg85 90 95Ser Lys Leu Ala Ala Phe Ile Asp Gln Asn Ile100 105210108211145212PRT213腎棒桿菌400108Met Ile Ile Val Cys Ala Ser Cys Gly Ala Lys Asn Arg Val Pro Glu1 5 10 15Glu Lys Leu Ala Val His Pro Asn Cys Gly Gln Cys His Gln Ala Leu20 25 30Leu Pro Leu Glu Pro Ile Glu Leu Asn Glu Gln Asn Phe Ser Asn Phe35 40 45Ile Ser Asn Ser Asp Leu Pro Val Leu Ile Asp Leu Trp Ala Glu Trp50 55 60Cys Gly Pro Cys Lys Met Met Ala Pro His Phe Ala Gln Val Ala Lys65 70 75 80Gln Asn Pro Tyr Val Val Phe Ala Lys Ile Asp Thr Glu Ala Asn Pro85 90 95Arg Leu Ser Ala Ala Phe Asn Val Arg Ser Ile Pro Thr Leu Val Leu100 105 110Met Asn Lys Thr Thr Glu Val Ala Arg Ile Ser Gly Ala Leu Arg Thr115 120 125Leu Glu Leu Gln Gln Trp Leu Asp Gln Gln Leu Gln Gln Gln Gln Gly130 135 140Asn145210109211107212PRT213酒色著色菌(Chromatium vinosum)220221VARIANT22217，38，42，55，58，60，72，107223Xaa＝任何胺基酸400109Ser Asp Ser Ile Val His Val Thr Asp Asp Ser Phe Glu Glu Glu Val1 5 10 15Xaa Lys Ser Pro Asp Pro Val Leu Val Asp Tyr Trp Ala Asp Trp Cys20 25 30Gly Pro Cys Lys Met Xaa Ala Pro Val Xaa Asp Glu Ile Ala Asp Glu35 40 45Tyr Ala Gly Arg Val Lys Xaa Ala Lys Xaa Asn Xaa Asp Glu Asn Pro50 55 60Asn Thr Pro Pro Arg Tyr Gly Xaa Arg Gly Ile Pro Thr Leu Met Leu65 70 75 80Phe Arg Gly Gly Glu Val Glu Ala Thr Lys Val Gly Ala Val Ser Lys85 90 95Ser Gln Leu Thr Ala Phe Leu Asp Ser Asn Xaa100 105210110211107212PRT213海濱梭菌(Clostridium litorale)400110Met Leu Met Leu Asp Lys Asp Thr Phe Lys Thr Glu Val Leu Glu Gly1 5 10 15Thr Gly Tyr Val Leu Val Asp Tyr Phe Ser Asp Gly Cys Val Pro Cys20 25 30Lys Ala Leu Met Pro Ala Val Glu Glu Leu Ser Lys Lys Tyr Glu Gly35 40 45Arg Val Val Phe Ala Lys Leu Asn Thr Thr Gly Ala Arg Arg Leu Ala50 55 60Ile Ser Gln Lys Ile Leu Gly Leu Pro Thr Leu Ser Leu Tyr Lys Asp65 70 75 80Gly Val Lys Val Asp Glu Val Thr Lys Asp Asp Ala Thr Ile Glu Asn85 90 95Ile Glu Ala Met Val Glu Glu His Ile Ser Lys100 10521011121140212PRT213產芽孢梭狀芽孢桿菌(Clostridium sporogenes)400111Met Leu Val Leu Asp Lys Lys Thr Phe Glu Glu Glu Val Leu Lys Thr1 5 10 15Lys Gly Tyr Val Leu Val Asp Tyr Phe Gly Asp Gly Cys Val Pro Cys20 25 30Glu Ala Leu Met Pro Asp Val Glu35 4021011221133212PRT213斯蒂克蘭德氏梭狀芽孢桿菌400112Met Phe Glu Leu Asp Lys Asp Thr Phe Glu Thr Glu Val Leu Gln Gly1 5 10 15Thr Gly Tyr Val Leu Val Asp Phe Trp Ser Glu Gly Cys Glu Pro Cys20 25 30Lys210113211106212PRT213Coprinus comatus400113Met Val Gln Val Ile Ser Asn Leu Asp Glu Phe Asn Lys Leu Thr Asn1 5 10 15Ser Gly Lys Ile Ile Ile Ile Asp Phe Trp Ala Thr Trp Cys Gly Pro20 25 30Cys Arg Val Ile ser Pro Ile Phe Glu Lys Phe Ser Glu Lys Tyr Gly35 40 45Ala Asn Asn Ile Val Phe Ala Lys Val Asp Val Asp Thr Ala Ser Asp
50 55 60Ile Ser Glu Glu Ala Lys Ile Arg Ala Met Pro Thr Phe Gln Val Tyr65 70 75 80Lys Asp Gly Gln Lys Ile Asp Glu Leu Val Gly Ala Asn Pro Thr Ala85 90 95Leu Glu Ser Leu Val Gln Lys Ser Leu Ala100 105210114211105212PRT213Dictyostelium discoideum400114Met Ser Asn Arg Val Ile His Val Ser Ser Cys Glu Glu Leu Asp Lys1 5 10 15His Leu Arg Asp Glu Arg Val Val Val Asp Phe Ser Ala Val Trp Cys20 25 30Gly Pro Cys Arg Ala Ile Ser Pro Val Phe Glu Lys Leu Ser Asn Glu35 40 45Phe Ile Thr Phe Thr Phe Leu His Val Asp Ile Asp Lys Leu Asn Val50 55 60His Pro Ile Val Ser Lys Ile Lys Ser Val Pro Thr Phe His Phe Tyr65 70 75 80Arg Asn Gly Ser Lys Val Ser Glu Phe Ser Gly Ala Ser Glu Ser Ile85 90 95Leu Arg Ser Thr Leu Glu Ala Asn Lys100 10521011521188212PRT213Dictyostelium discoideum400115Met Ser Arg Val Ile His Ile Ser Ser Asn Glu Glu Leu Asp Lys His1 5 10 15Leu Gln Ala Glu Arg Leu Val Ile Asp Phe Ser Ala Ala Trp Cys Gly20 25 30Pro Cys Arg Ala Ile Ser Pro Val phe Glu Lys Leu Ser Asn Glu Phe35 40 45Val Thr Phe Thr Phe Val His Val Asp Ile Asp Lys Leu Ser Gly His50 55 60Pro Ile Val Lys Glu Ile Arg Ser Val Pro Thr Phe Tyr phe Tyr Arg65 70 75 80Asn Gly Ala Lys Val Ser Glu Phe8521011621188212PRT213Dictyostelium discoideum400116Met Ser Arg Val Ile His Ile Ser Ser Asn Glu Glu Leu Asp Lys His1 5 10 15Leu Gln Ala Glu Arg Leu Val Ile Asp Phe Ser Ala Ala Trp Cys Gly20 25 30Pro Cys Arg Ala Ile Ser Pro Val Phe Glu Lys Leu Ser Asn Glu Phe35 40 45Val Thr Phe Thr Phe Val His Val Asp Ile Asp Lys Leu Ser Gly His50 55 60Pro Ile Val Lys Glu Ile Arg Ser Val Pro Thr Phe Tyr Phe Tyr Arg65 70 75 80Asn Gly Ala Lys Val Ser Glu Phe85210117211108212PRT213大腸埃希氏桿菌，鼠傷寒沙門氏菌(E coli，salmonella typhimurium)400117Ser Asp Lys Ile Ile His Leu Thr Asp Asp Ser Phe Asp Thr Asp Val1 5 10 15Leu Lys Ala Asp Gly Ala Ile Leu Val Asp Phe Trp Ala Glu Trp Cys20 25 30Gly Pro Cys Lys Met Ile Ala Pro Ile Leu Asp Glu Ile Ala Asp Glu35 40 45Tyr Gln Gly Lys Leu Thr Val Ala Lys Leu Asn Ile Asp Gln Asn Pro50 55 60Gly Thr Ala Pro Lys Tyr Gly Ile Arg Gly Ile Pro Thr Leu Leu Leu65 70 75 80Phe Lys Asn Gly Glu Val Ala Ala Thr Lys Val Gly Ala Leu Ser Lys85 90 95Gly Gln Leu Lys Glu Phe Leu Asp Ala Asn Leu Ala100 105210118211105212PRT213集胞藍細菌屬(Synechocystis)400118Met Ala Val Lys Lys Gln Phe Ala Asn Phe Ala Glu Met Leu Ala Gly1 5 10 15Ser Pro Lys Pro Val Leu Val Asp Phe Tyr Ala Thr Trp Cys Gly Pro20 25 30Cys Gln Met Met Ala Pro Ile Leu Glu Gln Val Gly Ser His Leu Arg35 40 45Gln Gln Ile Gln Val Val Lys Ile Asp Thr Asp Lys Tyr Pro Ala Ile50 55 60Ala Thr Gln Tyr Gln Ile Gln Ser Leu Pro Thr Leu Val Leu Phe Lys65 70 75 80Gln Gly Gln Pro Val His Arg Met Glu Gly Val Gln Gln Ala Ala Gln85 90 95Leu Ile Gln Gln Leu Gln Val Phe Val100 105210119211139212PRT213大腸桿菌400119Met Asn Thr Val Cys Thr His Cys Gln Ala Ile Asn Arg Ile Pro Asp1 5 10 15Asp Arg Ile Glu Asp Ala Ala Lys Cys Gly Arg Cys Gly His Asp Leu20 25 30Phe Asp Gly Glu Val Ile Asn Ala Thr Gly Glu Thr Leu Asp Lys Leu35 40 45Leu Lys Asp Asp Leu Pro Val Val Ile Asp Phe Trp Ala Pro Trp Cys50 55 60Gly Pro Cys Arg Asn Phe Ala Pro Ile Phe Glu Asp Val Ala Gln Glu65 70 75 80Arg Ser Gly Lys Val Arg Phe Val Lys Val Asn Thr Glu Ala Glu Arg85 90 95Glu Leu Ser Ser Arg Phe Gly Ile Arg Ser Ile Pro Thr Ile Met Ile
100 105 110Phe Lys Asn Gly Gln Val Val Asp Met Leu Asn Gly Ala Val Pro Lys115 120 125Ala Pro Phe Asp Ser Trp Leu Asn Glu Ser Leu130 135210120211110212PRT213嗜胺基酸真桿菌(Eubacterium acidaminophilum)400120Met Ser Ala Leu Leu Val Glu Ile Asp Lys Asp Gln Phe Gln Ala Glu1 5 10 15Val Leu Glu Ala Glu Gly Tyr Val Leu Val Asp Tyr Phe Ser Asp Gly20 25 30Cys Val Pro Cys Lys Ala Leu Met Pro Asp Val Glu Glu Leu Ala Ala35 40 45Lys Tyr Glu Gly Lys Val Ala Phe Arg Lys Phe Asn Thr Ser Ser Ala50 55 60Arg Arg Leu Ala Ile Ser Gln Lys Ile Leu Gly Leu Pro Thr Ile Thr65 70 75 80Leu Tyr Lys Gly Gly Gln Lys Val Glu Glu Val Thr Lys Asp Asp Ala85 90 95Thr Arg Glu Asn Ile Asp Ala Met Ile Ala Lys His Val Gly100 105 110210121211107212PRT213流感嗜血桿菌(Haemophilus influenzae)400121Met Ser Glu Val Leu His Ile Asn Asp Ala Asp Phe Glu Ser Val Val1 5 10 15Val Asn Ser Asp Ile Pro Ile Leu Leu Asp Phe Trp Ala Pro Trp Cys20 25 30Gly Pro Cys Lys Met Ile Ala Pro Val Leu Asp Glu Leu Ala Pro Glu35 40 45Phe Ala Gly Lys Val Lys Ile Val Lys Met Asn Val Asp Asp Asn Gln50 55 60Ala Thr Pro Ala Gln Phe Gly Val Arg Ser Ile Pro Thr Leu Leu Leu65 70 75 80Ile Lys Asn Gly Gln Val Val Ala Thr Gln Val Gly Ala Leu Pro Lys85 90 95Thr Gln Leu Ala Asn Phe Ile Asn Gln His Ile100 105210122211167212PRT213流感嗜血桿菌400122Met Lys Ile Lys Lys Leu Leu Lys Asn Gly Leu Ser Leu Phe Leu Thr1 5 10 15Phe Ile Val Ile Thr Ser Ile Leu Asp Phe Val Arg Arg Pro Val Val20 25 30Pro Glu Glu Ile Asn Lys Ile Thr Leu Gln Asp Leu Gln Gly Asn Thr35 40 45Phe Ser Leu Glu Ser Leu Asp Gln Asn Lys Pro Thr Leu Leu Tyr Phe50 55 60Trp Gly Thr Trp Cys Gly Tyr Cys Arg Tyr Thr Ser Pro Ala Ile Asn65 70 75 80Ser Leu Ala Lys Glu Gly Tyr Gln Val Val Ser Val Ala Leu Arg Ser85 90 95Gly Asn Glu Ala Asp Val Asn Asp Tyr Leu Ser Lys Asn Asp Tyr His100 105 110Phe Thr Thr Val Asn Asp Pro Lys Gly Glu Phe Ala Glu Arg Trp Gln115 120 125Ile Asn Val Thr Pro Thr Ile Val Leu Leu Ser Lys Gly Lys Met Asp130 135 140Lau Val Thr Thr Gly Leu Thr Ser Tyr Trp Gly Leu Lys Val Arg Leu145 150 155 160Phe Phe Ala Glu Phe Phe Gly165210123211106212PRT213幽門螺桿菌400123Met Ser His Tyr Ile Glu Leu Thr Glu Glu Asn Phe Glu Ser Thr Ile1 5 10 15Lys Lys Gly Val Ala Leu Val Asp Phe Trp Ala Pro Trp Cys Gly Pro20 25 30Cys Lys Met Leu Ser Pro Val Ile Asp Glu Leu Ala Ser Glu Tyr Glu35 40 45Gly Lys Ala Lys Ile Cys Lys Val Asn Thr Asp Glu Gln Glu Glu Leu50 55 60Ser Ala Lys Phe Gly Ile Arg Ser Ile Pro Thr Leu Leu Phe Thr Lys65 70 75 80Asp Gly Glu Val Val His Gln Leu Val Gly Val Gln Thr Lys Val Ala85 90 95Leu Lys Glu Gln Leu Asn Lys Leu Leu Gly100 105210124211103212PRT213單核細胞增生利斯特氏菌400124Met Val Lys Glu Ile Thr Asp Ala Thr Phe Glu Gln Glu Thr Ser Glu1 5 10 15Gly Leu Val Leu Thr Asp Phe Trp Ala Thr Trp Cys Gly Pro Cys Arg20 25 30Met Val Ala Pro Val Leu Glu Glu Ile Gln Glu Glu Arg Gly Glu Ala35 40 45Leu Lys Ile Val Lys Met Asp Val Asp Glu Asn Pro Glu Thr Pro Gly50 55 60Ser Phe Gly Val Met Ser Ile Pro Thr Leu Leu Ile Lys Lys Asp Gly65 70 75 80Glu Val Val Glu Thr Ile Ile Gly Tyr Arg Pro Lys Glu Glu Leu Asp85 90 95Glu Val Ile Asn Lys Tyr Val10021012521185212PRT213詹氏甲烷球菌(Methoanococus jannaschii)400125Met Ser Lys Val Lys Ile Glu Leu Phe Thr Ser Pro Met Cys Pro His1 5 10 15Cys Pro Ala Ala Lys Arg Val Val Glu Glu Val Ala Asn Glu Met Pro
20 25 30Asp Ala Val Glu Val Glu Tyr Ile Asn Val Met Glu Asn Pro Gln Lys35 40 45Ala Met Glu Tyr Gly Ile Met Ala Val Pro Thr Ile Val Ile Asn Gly50 55 60Asp Val Glu Phe Ile Gly Ala Pro Thr Lys Glu Ala Leu Val Glu Ala65 70 75 80Ile Lys Lys Arg Leu85210126211102212PRT213生殖道枝原體400126Met Val Thr Glu Ile Arg Ser Leu Lys Gln Leu Glu Glu Ile Phe Ser1 5 10 15Ala Lys Lys Asn Val Ile Val Asp Phe Trp Ala Ala Trp Cys Gly Pro20 25 30Cys Lys Leu Thr Ser Pro Glu Phe Gln Lys Ala Ala Asp Glu Phe Ser35 40 45Asp Ala Gln Phe Val Lys Val Asn Val Asp Asp His Thr Asp Ile Ala50 55 60Ala Ala Tyr Asn Ile Thr Ser Leu Pro Thr Ile Val Val Phe Glu Asn65 70 75 80Gly Val Glu Lys Lys Arg Ala Ile Gly Phe Met Pro Lys Thr Lys Ile85 90 95Ile Asp Leu Phe Asn Asn100210127211458212PRT213麻瘋分枝桿菌400127Met Asn Thr Thr Pro Ser Ala His Glu Thr Ile His Glu Val Ile Val1 5 10 15Ile Gly Ser Gly Pro Ala Gly Tyr Thr Ala Ala Leu Tyr Ala Ala Arg20 25 30Ala Gln Leu Thr Pro Leu Val Phe Glu Gly Thr Ser Phe Gly Gly Ala35 40 45Leu Met Thr Thr Thr Glu Val Glu Asn Tyr Pro Gly Phe Arg Asn Gly50 55 60Ile Thr Gly Pro Glu Leu Met Asp Asp Met Arg Glu Gln Ala Leu Arg65 70 75 80Phe Gly Ala Glu Leu Arg Thr Glu Asp Val Glu Ser Val Ser Leu Arg85 90 95Gly Pro Ile Lys Ser Val Val Thr Ala Glu Gly Gln Thr Tyr Gln Ala100 105 110Arg Ala Val Ile Leu Ala Met Gly Thr Ser Val Arg Tyr Leu Gln Ile115 120 125Pro Gly Glu Gln Glu Leu Leu Gly Arg Gly Val Ser Ala Cys Ala Thr130 135 140Cys Asp Gly Ser Phe Phe Arg Gly Gln Asp Ile Ala Val Ile Gly Gly145 150 155 160Gly Asp Ser Ala Met Glu Glu Ala Leu Phe Leu Thr Arg Phe Ala Arg165 170 175Ser Val Thr Leu Val His Arg Arg Asp Glu Phe Arg Ala Ser Lys Ile180 185 190Met Leu Gly Arg Ala Arg Asn Asn Asp Lys Ile Lys Phe Ile Thr Asn195 200 205His Thr Val Val Ala Val Asn Gly Tyr Thr Thr Val Thr Gly Leu Arg210 215 220Leu Arg Asn Thr Thr Thr Gly Glu Glu Thr Thr Leu Val Val Thr Gly225 230 235 240Val Phe Val Ala Ile Gly His Glu Pro Arg Ser Ser Leu Val Ser Asp245 250 255Val Val Asp Ile Asp Pro Asp Gly Tyr Val Leu Val Lys Gly Arg Thr260 265 270Thr Ser Thr Ser Met Asp Gly Val Phe Ala Ala Gly Asp Leu Val Asp275 280 285Arg Thr Tyr Arg Gln Ala Ile Thr Ala Ala Gly Ser Gly Cys Ala Ala290 295 300Ala Ile Asp Ala Glu Arg Trp Leu Ala Glu His Ala Gly Ser Lys Ala305 310 315 320Asn Glu Thr Thr Glu Glu Thr Gly Asp Val Asp Ser Thr Asp Thr Thr325 330 335Asp Trp Ser Thr Ala Met Thr Asp Ala Lys Asn Ala Gly Val Thr Ile340 345 350Glu Val Thr Asp Ala Ser Phe Phe Ala Asp Val Leu Ser Ser Asn Lys355 360 365Pro Val Leu Val Asp Phe Trp Ala Thr Trp Cys Gly Pro Cys Lys Met370 375 380Val Ala Pro Val Leu Glu Glu Ile Ala Ser Glu Gln Arg Asn Gln Leu385 390 395 400Thr Val Ala Lys Leu Asp Val Asp Thr Asn Pro Glu Met Ala Arg Glu405 410 415Phe Gln Val Val Ser Ile Pro Thr Met Ile Leu Phe Gln Gly Gly Gln420 425 430Pro Val Lys Arg Ile Val Gly Ala Lys Gly Lys Ala Ala Leu Leu Arg435 440 445Asp Leu Ser Asp Val Val Pro Asn Leu Asn450 455210128211102212PRT213肺炎枝原體(Mycoplasma pneumoniae)400128Met Val Thr Glu Ile Lys Ser Leu Lys Gln Leu Gly Glu Leu Phe Ala1 5 10 15Ser Asn Asn Lys Val Ile Ile Asp phe Trp Ala Glu Trp Cys Gly Pro20 25 30Cys Lys Ile Thr Gly Pro Glu Phe Ala Lys Ala Ala Ser Glu Val Ser35 40 45Thr Val Ala Phe Ala Lys Val Asn Val Asp Glu Gln Thr Asp Ile Ala50 55 60Ala Ala Tyr Lys Ile Thr Ser Leu Pro Thr Ile Val Leu Phe Glu Lys65 70 75 80Gly Gln Glu Lys His Arg Ala Ile Gly Phe Met Pro Lys Ala Lys Ile85 90 95Val Gln Leu Val Ser Gln100210129211112212PRT213恥垢分枝桿菌(Mycobacterium smegmatis)400129Met Ser Glu Asp Ser Ala Thr Val Ala Val Thr Asp Asp Ser Phe Ser1 5 10 15Thr Asp Val Leu Gly Ser Ser Lys Pro Val Leu Val Asp Phe Trp Ala20 25 30Thr Trp Cys Gly Pro Cys Lys Met Val Ala Pro Val Leu Glu Glu Ile35 40 45Ala Ala Glu Lys Gly Asp Gln Leu Thr Val Ala Lys Ile Asp Val Asp
50 55 60Val Asp Ala Asn Pro Ala Thr Ala Arg Asp Phe Gln Val Val Ser Ile65 70 75 80Pro Thr Met Ile Leu Phe Lys Asp Gly Ala Pro Val Lys Arg Ile Val85 90 95Gly Ala Lys Gly Lys Ala Ala Leu Leu Arg Glu Leu Ser Asp Ala Leu100 105 110210130211115212PRT213結核分枝桿菌400130Thr Asp Ser Glu Lys Ser Ala Thr Ile Lys Val Thr Asp Ala Ser Phe1 5 10 15Ala Thr Asp Val Leu Ser Ser Asn Lys Pro Val Leu Val Asp Phe Trp20 25 30Ala Thr Trp Cys Gly Pro Cys Lys Met Val Ala Pro Val Leu Glu Glu35 40 45Ile Ala Thr Glu Arg Ala Thr Asp Leu Thr Val Ala Lys Leu Asp Val50 55 60Asp Thr Asn Pro Glu Thr Ala Arg Asn Phe Gln Val Val Ser Ile Pro65 70 75 80Thr Leu Ile Leu Phe Lys Asp Gly Gln Pro Val Lys Arg Ile Val Gly85 90 95Ala Lys Gly Lys Ala Ala Leu Leu Arg Glu Leu Ser Asp Val Val Pro100 105 110Asn Leu Asn115210131211127212PRT213粗糙鏈孢黴400131Met Ser Asp Gly Val Lys His Ile Asn Ser Ala Gln Glu Phe Ala Asn1 5 10 15Leu Leu Asn Thr Thr Gln Tyr Val Val Ala Asp Phe Tyr Ala Asp Trp20 25 30Cys Gly Pro Cys Lys Ala Ile Ala Pro Met Tyr Ala Gln Phe Ala Lys35 40 45Thr Phe Ser Ile Pro Asn Phe Leu Ala Phe Ala Lys Ile Asn Val Asp50 55 60Ser Val Gln Gln Val Ala Gln His Tyr Arg Val Ser Ala Met Pro Thr65 70 75 80Phe Leu Phe Phe Lys Asn Gly Lys Gln Val Ala Val Asn Gly Ser Val85 90 95Met Ile Gln Gly Ala Asp Val Asn Ser Leu Arg Ala Ala Ala Glu Lys100 105 110Met Gly Arg Leu Ala Lys Glu Lys Ala Ala Ala Ala Gly Ser Ser115 120 125210132211106212PRT213產黃青黴400132Met Gly Val Thr Pro Ile Lys Ser Val Ala Glu Tyr Lys Glu Lys Val1 5 10 15Thr Asp Ala Thr Gly Pro Val Val Val Asp Phe His Ala Thr Trp Cys20 25 30Gly Pro Cys Lys Ala Ile Ala Pro Ala Leu Glu Lys Leu Ser Glu Thr35 40 45His Thr Gly Ile Gln Phe Tyr Lys Val Asp Val Asp Glu Leu Ser Glu50 55 60Val Ala Ala Ser Asn Gly Val Ser Ala Met Pro Thr Phe His Phe Tyr65 70 75 80Lys Gly Gly Glu Arg Asn Glu Glu Val Lys Gly Ala Asn Pro Ala Ala85 90 95Ile Gln Ala Gly Val Lys Ala Ile Leu Glu100 105210133211108212PRT213銅綠假單胞菌400133Met Ser Glu His Ile Val Asn Val Thr Asp A1a Ser Phe Glu Gln Asp1 5 10 15Val Leu Lys Ala Asp Gly Pro Val Leu Val Asp Tyr Trp Ala Glu Trp20 25 30Cys Gly Pro Cys Lys Met Ile Ala Pro Val Leu Asp Glu Val Ala Arg35 40 45Asp Tyr Gln Gly Lys Leu Lys Val Cys Lys Leu Asn Ile Asp Glu Asn50 55 60Gln Asp Thr Pro Pro Lys Tyr Gly Val Arg Gly Ile Pro Thr Leu Met65 70 75 80Leu Phe Lys Asp Gly Asn Val Glu Ala Thr Lys Val Gly Ala Leu Ser85 90 95Lys Ser Gln Leu Ala Ala Phe Leu Asp Ala Asn Ile100 105210134211104212PRT213深紅螺菌220221VARIANT22221，35223Xaa＝Any Amino Acid400134Met Lys Gln Val Ser Asp Ala Ser Phe Glu Glu Asp Val Leu Lys Ala1 5 10 15Asp Gly Pro Asn Xaa Val Asp Phe Trp Ala Glu Trp Cys Gly Pro Cys20 25 30Arg Gln Xaa Ala Pro Ala Leu Glu Glu Leu Ala Thr Ala Leu Gly Asp35 40 45Lys Val Thr Val Ala Lys Ile Asn Ile Asp Glu Asn Pro Gln Thr Pro50 55 60Ser Lys Tyr Gly Val Arg Gly Ile Pro Thr Leu Met Ile Phe Lys Asp65 70 75 80Gly Gln Val Ala Ala Thr Lys Ile Gly Ala Leu Pro Lys Thr Lys Leu85 90 95Phe Glu Trp Val Glu Ala Ser Val100210135211105212PRT213球形紅假單胞菌400135Ser Thr Val Pro Val Thr Asp Ala Thr Phe Asp Thr Glu Val Arg Lys1 5 l0 15Ser Asp Val Pro Vsl Val Val Asp Phe Trp Ala Glu Trp Cys Gly Pro20 25 30Cys Arg Gln Ile Gly Pro Ala Leu Glu Glu Leu Ser Lys Glu Tyr Ala35 4045Gly Lys Val Lys Ile Val Lys Val Asn Val Asp Glu Asn Pro Glu Ser50 55 60Pro Ala Met Leu Gly Val Arg Gly Ile Pro Ala Leu Phe Leu Phe Lys65 70 75 80Asn Gly Gln Val Val Ser Asn Lys Val Gly Ala Ala Pro Lys Ala Ala85 90 95Leu Ala Thr Trp Ile Ala Ser Ala Leu100 105210136211130212PRT213普魯畫斯克氏立克次氏體400136Met Ser Cys Tyr Asn Glu Ile Thr Thr Leu Leu Glu Phe Asp Ser Asn1 5 10 15Asp Ile Asn Thr Thr Gln Arx Ile Asn Met Val Asn Asn Val Thr Asp20 25 30Ser Ser Phe Lys Asn Glu Val Leu Glu Ser Asp Leu Pro Val Met Val35 40 45Asp Phe Trp Ala Glu Trp Cys Gly Pro Cys Lys Met Leu Ile Pro Ile50 55 60Ile Asp Glu Ile Ser Lys Glu Leu Gln Asp Lys Val Lys Val Leu Lys65 70 75 80Met Asn Ile Asp Glu Asn Pro Lys Thr Pro Ser Glu Tyr Gly Ile Arg85 90 95Ser Ile Pro Thr Ile Met Leu Phe Lys Asn Gly Glu Gln Lys Asp Thr100 105 110Lys Ile Gly Leu Gln Gln Lys Asn Ser Leu Leu Asp Trp Ile Asn Lys115 120 125Ser Ile130210137211106212PRT213金黴素鏈黴菌400137Gly Ala Thr Val Lys Val Thr Asn Ala Thr Phe Lys Ser Asp Val Leu1 5 10 15Glu Ser Asp Lys Pro Val Leu Val His Phe Glu Gly Pro Trp Cys Gly20 25 30Pro Cys Lys Met Val Ala Pro Val Leu Asp Glu Ile Ala Asn Glu Tyr35 40 45Glu Gly Lys Val Lys Val Ala Lys Val Asn Thr Asp Glu Asn Pro Gln50 55 60Leu Ala Ser Gln Tyr Gly Val Arg Ser Ile Pro Thr Arg Leu Met Phe65 70 75 80Lys Gly Gly Glu Val Ala Ala Asn Met Val Gly Ala Ala Pro Lys Thr85 90 95Arg Leu Ala Ala Phe Leu Asp Ala Ser Leu100 105210138211110212PRT213天藍色鏈黴菌(Streptomyces coelicolor)400138Met Ala Gly Thr Leu Lys His Val Thr Asp Asp Ser Phe Glu Gln Asp1 5 10 15Val Leu Lys Asn Asp Lys Pro Val Leu Val Asp Phe Trp Ala Ala Trp20 25 30Cys Gly Pro Cys Arg Gln Ile Ala Pro Ser Leu Glu Ala Ile Ala Ala35 40 45Glu Tyr Gly Asp Lys Ile Glu Ile Val Lys Leu Asn Ile Asp Glu Asn50 55 60Pro Gly Thr Ala Ala Lys Tyr Gly Val Met Ser Ile Pro Thr Leu Asn65 70 75 80Val Tyr Gln Gly Gly Glu Val Ala Lys Thr Ile Val Gly Ala Lys Pro85 90 95Lys Ala Ala Ile Val Arg Asp Leu Glu Asp Phe Ile Ala Asp210139211107212PRT213帶棒鏈黴菌(Streptomyces clavuligerus)400139Met Ala Gly Val Leu Lys Asn Val Thr Asp Asp Thr Phe Glu Ala Asp1 5 10 15Val Leu Lys Ser Glu Lys Pro Val Leu Val Asp Phe Trp Ala Glu Trp20 25 30Cys Gly Pro Cys Arg Gln Ile Ala Pro Ser Leu Glu Ala Ile Thr Glu35 40 45His Gly Gly Gln Ile Glu Ile Val Lys Leu Asn Ile Asp Gln Asn Pro50 55 60Ala Thr Ala Ala Lys Tyr Gly Val Met Ser Ile Pro Thr Leu Asn Val65 70 75 80Tyr Gln Gly Gly Glu Val Val Lys Thr Ile Val Gly Ala Lys Pro Lys85 90 95Ala Ala Leu Leu Arg Pro Gly Pro Val Pro Arg100 105210140211106212PRT213集胞藍細菌屬400140Ser Ala Thr Pro Gln Val Ser Asp Ala Ser Phe Lys Glu Asp Val Leu1 5 10 15Asp Ser Glu Leu Pro Val Leu Val Asp Phe Trp Ala Pro Trp Cys Gly20 25 30Pro Cys Arg Met Val Ala Pro Val Val Asp Glu Ile Ser Gln Gln Tyr35 40 45Glu Gly Lys Val Lys Val Val Lys Leu Asn Thr Asp Glu Asn Pro Asn50 55 60Thr Ala Ser Gln Tyr Gly Ile Arg Ser Ile Pro Thr Leu Met Ile Phe65 70 75 80Lys Gly Gly Gln Arg Val Asp Met Val Val Gly Ala Val Pro Lys Thr85 90 95Thr Leu Ala Ser Thr Leu Glu Lys Tyr Leu100 105210141211109212PRT213集胞藍細菌屬400141Met Ser Leu Leu Glu Ile Thr Asp Ala Glu Phe Glu Gln Glu Thr Gln1 5 10 15Gly Gln Thr Lys Pro Val Leu Val Tyr Phe Trp Ala Ser Trp Cys Gly20 25 30Pro Cys Arg Leu Met Ala Pro Ala Ile Gln Ala Ile Ala Lys Asp Tyr35 40 45Gly Asp Lys Leu Lys Val Leu Lys Leu Glu Val Asp Pro Asn Pro Ala50 55 60Ala Val Ala Gln Cys Lys Val Glu Gly Val Pro Ala Leu Arg Leu Phe65 70 75 80Lys Asn Asn Glu Lau Val Met Thr His Glu Gly Ala Ile Ala Lys Pro85 90 95Lys Lau Leu Glu Leu Leu Lys Glu Glu Leu Asp Phe Ile100 105210142211108212PRT213氧化亞鐵硫芽孢桿菌(Thiobacillus ferrooxidans)400142Met Ser Asp Ala Ile Leu Tyr Val Ser Asp Asp Ser Phe Glu Thr Asp1 5 10 15Val Leu Lys Ser Ser Lys Pro Val Leu Val Asp Phe Trp Ala Glu Trp20 25 30Cys Gly Pro Cys Lys Met Ile Ala Pro Ile Leu Glu Glu Ile Ala Asp35 40 45Glu Tyr Ala Asp Arg Leu Arg Val Ala Lys Phe Asn Ile Asp Glu Asn50 55 60Pro Asn Thr Pro Pro Gln Tyr Ala Ile Arg Gly Ile Pro Thr Leu Leu65 70 75 80Leu Phe Lys Ala Gly Lys Leu Glu Ala Thr Lys Val Gly Ala Leu Ser85 90 95Lys Ala Gln Leu Thr Ala Phe Leu Asp Ser Gln Leu100 10521014321191212PRT213桃紅莢硫菌400143Met Ser Asp Ser Ile Val His Val Thr Asp Asp Ser Phe Glu Asp Glu1 5 10 15Val Leu Lys Ser Leu Glu Pro Val Leu Val Asp Tyr Trp Ala Asp Trp20 25 30Cys Gly Pro Cys Lys Met Ile Ala Pro Val Leu Asp Glu Ile Ala Gly35 40 45Glu Tyr Ala Gly Arg Ile Lys Val Ala Lys Leu Asn Ile Asp Glu Asn50 55 60Pro Ash Thr Pro Arg Arg Tyr Gly Ile Arg Gly Ile Pro Thr Leu Met65 70 75 80Leu Ser Arg Gln Ser Glu Val Glu Ala Thr Lys85 9021014421144212PRT213Tissierella creatinophila400144Met Ile Glu Leu Asp Lys Ser Asn Phe Glu Glu Glu Val Leu Lys Ala1 5 10 15Glu Gly Thr Val Leu Val Asp Phe Trp Ser Pro Ser Cys Glu Pro Cys20 25 30Lys Ala Leu Met Pro His Val His Asp Phe Glu Glu35 40210145211105212PRT213蒼白密螺旋體400145Met Ala Leu Leu Asp Ile Ser Ser Gly Asn Val Arg Lys Thr Ile Glu1 5 10 15Thr Asn Pro Leu Val Ile Val Asp Phe Trp Ala Pro Trp Cys Gly Ser20 25 30Cys Lys Met Leu Gly Pro Val Leu Glu Glu Val Glu Ser Glu Val Gly35 40 45Ser Gly Val Val Ile Gly Lys Leu Asn Val Asp Asp Asp Gln Asp Leu50 55 60Ala Val Glu Phe Asn Val Ala Ser Ile Pro Thr Leu Ile Val Phe Lys65 70 75 80Asp Gly Lys Glu Val Asp Arg Ser Ile Gly Phe Val Asp Lys Ser Lys85 90 95Ile Leu Thr Leu Ile Gln Lys Asn Ala100 105210146211104212PRT213Bos taurus400146Val Lys Gln Ile Glu Ser Lys Tyr Ala Phe Gln Glu Ala Leu Asn Ser1 5 10 15Ala Gly Glu Lys Leu Val Val Val Asp Phe Ser Ala Thr Trp Cys Gly20 25 30Pro Cys Lys Met Ile Lys Pro Phe Phe His Ser Leu Ser Glu Lys Tyr35 40 45Ser Asn Val Val Phe Leu Glu Val Asp Val Asp Asp Cys Gln Asp Val50 55 60Ala Ala Glu Cys Glu Val Lys Cys Met Pro Thr Phe Gln Phe Phe Lys65 70 75 80Lys Gly Gln Lys Val Gly Glu Phe Ser Gly Ala Asn Lys Glu Lys Leu85 90 95Glu Ala Thr Ile Asn Glu Leu Ile100210147211166212PRT213Bos taurus400147Met Ala Gln Arg Leu Leu Leu Arg Arg Phe Leu Thr Ser Ile Ile Ser1 5 10 15Gly Lys Pro Ser Gln Ser Arg Trp Ala Pro Val Ala Ser Arg Ala Leu20 25 30Lys Thr Pro Gln Tyr Ser Pro Gly Tyr Leu Thr Val Thr Pro Ser Gln35 40 45Ala Arg Ser Ile Tyr Thr Thr Arg Val Cys Ser Thr Thr Phe Asn Ile50 55 60Gln Asp Gly Pro Asp Phe Gln Asp Arg Val Val Asn Ser Glu Thr Pro65 70 75 80Val Val Val Asp Phe His Ala Gln Trp Cys Gly Pro Cys Lys Ile Leu
85 90 95Gly Pro Arg Leu Glu Lys Val Val Ala Lys Gln His Gly Lys Val Val100 105 110Met Ala Lys Val Asp Ile Asp Asp His Thr Asp Leu Ala Leu Glu Tyr115 120 125Glu Val Ser Ala Val Pro Thr Val Leu Ala Met Lys Asn Gly Asp Val130 135 140Val Asp Lys Phe Val Gly Ile Lys Asp Glu Asp Gln Leu Glu Ala Phe145 150 155 160Leu Lys Lys Leu Ile Gly165210148211115212PRT213Caenorhabditis elegans400148Met Leu Lys Arg Cys Asn Phe Lys Asn Gln Val Lys Tyr Phe Gln Ser1 5 10 15Asp Phe Glu Gln Leu Ile Arg Gln His Pro Glu Lys Ile Ile Ile Leu20 25 30Asp Phe Tyr Ala Thr Trp Cys Gly Pro Cys Lys Ala Ile Ala Pro Leu35 40 45Tyr Lys Glu Leu Ala Thr Thr His Lys Gly Ile Ile Phe Cys Lys Val50 55 60Asp Val Asp Glu Ala Glu Asp Leu Cys Ser Lys Tyr Asp Val Lys Met65 70 75 80Met Pro Thr Phe Ile Phe Thr Lys Asn Gly Asp Ala Ile Glu Ala Leu85 90 95Glu Gly Cys Val Glu Asp Glu Leu Arg Gln Lys Val Leu Glu His Val100 105 110Ser Ala Gln11521014921120212PRT213Canis familiaris400149Val Lys Gln Ile Glu Phe Lys Tyr Ala Phe Gln Glu Ala Leu Asn Ser1 5 10 15Ala Gly Asp Lys20210150211104212PRT213Gallus gallus400150Val Lys Ser Val Gly Asn Leu Ala Asp Phe Glu Ala Glu Leu Lys Ala1 5 10 15Ala Gly Glu Lys Leu Val Val Val Asp Phe Ser Ala Thr Trp Cys Gly20 25 30Pro Cys Lys Met Ile Lys Pro Phe Phe His Ser Leu Cys Asp Lys Phe35 40 45Gly Asp Val Val Phe Ile Glu Ile Asp Val Asp Asp Ala Gln Asp Val50 55 60Ala Thr His Cys Asp Val Lys Cys Met Pro Thr Phe Gln Phe Tyr Lys65 70 75 80Asn Gly Lys Lys Val Gln Glu Phe Ser Gly Ala Asn Lys Glu Lys Leu85 90 95Glu Glu Thr Ile Lys Ser Leu Val100210151211107212PRT213黃果蠅(Drosophila melanogaster)400151Met Ala Ser Val Arg Thr Met Asn Asp Tyr His Lys Arg Ile Glu Ala1 5 10 15Ala Asp Asp Lys Leu Ile Val Leu Asp Phe Tyr Ala Thr Trp Cys Gly20 25 30Pro Cys Lys Glu Met Glu Ser Thr Val Lys Ser Leu Ala Arg Lys Tyr35 40 45Ser Ser Lys Ala Val Val Leu Lys Ile Asp Val Asp Lys Phe Glu Glu50 55 60Leu Thr Glu Arg Tyr Lys Val Arg Ser Met Pro Thr Phe Val Phe Leu65 70 75 80Arg Gln Asn Arg Arg Leu Ala Ser Phe Ala Gly Ala Asp Glu His Lys85 90 95Leu Thr Asn Met Met Ala Lys Leu Val Lys Ala100 105210152211104212PRT213人400152Val Lys Gln Ile Glu Ser Lys Thr Ala Phe Gln Glu Ala Leu Asp Ala1 5 10 15Ala Gly Asp Lys Leu Val Val Val Asp Phe Ser Ala Thr Trp Cys Gly20 25 30Pro Cys Lys Met Ile Lys Pro Phe Phe His Ser Leu Ser Glu Lys Tyr35 40 45Ser Asn Val Ile Phe Leu Glu Val Asp Val Asp Asp Cys Gln Asp Val50 55 60Ala Ser Glu Cys Glu Val Lys Cys Met Pro Thr Phe Gln Phe Phe Lys65 70 75 80Lys Gly Gln Lys Val Gly Glu Phe Ser Gly Ala Asn Lys Glu Lys Leu85 90 95Glu Ala Thr Ile Asn Glu Leu Val100210153211166212PRT213人400153Met Ala Gln Arg Leu Leu Leu Arg Arg Phe Leu Ala Ser Val Ile Ser1 5 10 15Arg Lys Pro Ser Gln Gly Gln Trp Pro Pro Leu Thr Ser Lys Ala Leu20 25 30Gln Thr Pro Gln Cys Ser Pro Gly Gly Leu Thr Val Thr Pro Asn Pro35 40 45Ala Arg Thr Ile Tyr Thr Thr Arg Ile Ser Leu Thr Thr Phe Asn Ile50 55 60Gln Asp Gly Pro Asp Phe Gln Asp Arg Val Val Asn Ser Glu Thr Pro65 70 75 80Val Val Val Asp Phe His Ala Gln Trp Cys Gly Pro Cys Lys Ile Leu85 90 95Gly Pro Arg Leu Glu Lys Met Val Ala Lys Gln His Gly Lys Val Val
100 105 110Met Ala Lys Val Asp Ile Asp Asp His Thr Asp Leu Ala Ile Glu Tyr115 120 125Glu Val Ser Ala Val Pro Thr Val Leu Ala Met Lys Asn Gly Asp Val130 135 140Val Asp Lys Phe Val Gly Ile Lys Asp Glu Asp Gln Leu Glu Ala Phe145 150 155 160Leu Lys Lys Leu Ile Gly165210154211104212PRT213恆河猴(Macaca mulatta)400154Val Lys Gln Ile Glu Ser Lys Ala Ala Phe Gln Glu Ala Leu Asp Asp1 5 10 15Ala Gly Asp Lys Leu Val Val Val Asp Phe Ser Ala Thr Trp Cys Gly20 25 30Pro Cys Lys Met Ile Lys Pro Phe Phe His Ser Leu Ser Glu Lys Tyr35 40 45Ser Asn Val Val Phe Leu Glu Val Asp Val Asp Asp Cys Gln Asp Val50 55 60Ala Ser Glu Cys Glu Val Lys Cys Met Pro Thr Phe Gln Phe Phe Lys65 70 75 80Lys Gly Gln Lys Val Gly Glu Phe Ser Gly Ala Asn Lys Glu Lys Leu85 90 95Glu Ala Thr Ile Asn Glu Leu Val100210155211104212PRT213臺灣鼷鼠(Mus musculus)400155Val Lys Leu Ile Glu Ser Lys Glu Ala Phe Gln Glu Ala Leu Ala Ala1 5 10 15Ala Gly Asp Lys Leu Val Val Val Asp Phe Ser Ala Thr Trp Cys Gly20 25 30Pro Cys Lys Met Ile Lys Pro Phe Phe His Ser Leu Cys Asp Lys Tyr35 40 45Ser Asn Val Val Phe Leu Glu Val Asp Val Asp Asp Cys Gln Asp Val50 55 60Ala Ala Asp Cys Glu Val Lys Cys Met Pro Thr Phe Gln Phe Tyr Lys65 70 75 80Lys Gly Gln Lys Val Gly Glu Phe Ser Gly Ala Asn Lys Glu Lys Leu85 90 95Glu Ala Ser Ile Thr Glu Tyr Ala100210156211166212PRT213臺灣鼷鼠400156Met Ala Gln Arg Leu Leu Leu Gly Arg Phe Leu Thr Ser Val Ile Ser1 5 10 15Arg Lys Pro Pro Gln Gly Val Trp Ala Ser Leu Thr Ser Lys Thr Leu20 25 30Gln Thr Pro Gln Tyr Asn Ala Gly Gly Leu Thr Val Met Pro Ser Pro35 40 45Ala Arg Thr Val His Thr Thr Arg Val Cys Leu Thr Thr Phe Asn Val50 55 60Gln Asp Gly Pro Asp Phe Gln Asp Arg Val Val Asn Ser Glu Thr Pro65 70 75 80Val Val Val Asp Phe His Ala Gln Trp Cys Gly Pro Cys Lys Ile Leu85 90 95Gly Pro Arg Leu Glu Lys Met Val Ala Lys Gln His Gly Lys Val Val100 105 110Met Ala Lys Val Asp Ile Asp Asp His Thr Asp Leu Ala Ile Glu Tyr115 120 125Glu Val Ser Ala Val Pro Thr Val Leu Ala Ile Lys Asn Gly Asp Val130 135 140Val Asp Lys Phe Val Gly Ile Lys Asp Glu Asp Gln Leu Glu Ala Phe145 150 155 160Leu Lys Lys Leu Ile Gly16521015721133212PRT213野豬400157Val Lye Gln Ile Glu Ser Lys Tyr Ala Phe Gln Glu Ala Leu Asn Ser1 5 10 15Ala Gly Glu Lys Leu Val Val Val Asp Phe Ser Ala Thr Trp Cys Gly20 25 30Pro210158211104212PRT213穴免400158Val Lys Gln Ile Glu Ser Lys Ser Ala Phe Gln Glu Val Leu Asp Ser1 5 10 15Ala Gly Asp Lys Leu Val Val Val Asp Phe Ser Ala Thr Trp Cys Gly20 25 30Pro Cys Lys Met Ile Lys Pro Phe Phe His Ala Leu Ser Glu Lys Phe35 40 45Asn Asn Val Val Phe Ile Glu Val Asp Val Asp Asp Cys Lys Asp Ile50 55 60Ala Ala Glu Cys Glu Val Lys Cys Met Pro Thr Phe Gln Phe Phe Lys65 70 75 80Lys Gly Gln Lys Val Gly Glu Phe Ser Gly Ala Asn Lys Glu Lys Leu85 90 95Glu Ala Thr Ile Asn Glu Leu Leu100210159211104212PRT213褐鼠400159Val Lys Leu Ile Glu Ser Lys Glu Ala Phe Gln Glu Ala Leu Ala Ala1 5 10 15Ala Gly Asp Lys Leu Val Val Val Asp Phe Ser Ala Thr Trp Cys Gly20 25 30Pro Cys Lys Met Ile Lys Pro Phe Phe His Ser Leu Cys Asp Lys Tyr35 40 45Ser Asn Val Val Phe Leu Glu Val Asp Val Asp Asp Cys Gln Asp Val
50 55 60Ala Ala Asp Cys Glu Val Lys Cys Met Pro Thr Phe Gln Phe Tyr Lys65 70 75 80Lys Gly Gln Lys Val Gly Glu Phe Ser Gly Ala Asn Lys Glu Lys Leu85 90 95Glu Ala Thr Ile Thr Glu Phe Ala100210160211166212PRT213褐鼠400160Met Ala Gln Arg Leu Leu Leu Arg Arg Phe Leu Thr Ser Val Ile Ser1 5 10 15Arg Lys Pro Pro Gln Gly Val Trp Ala Ser Leu Thr Ser Thr Ser Leu20 25 30Gln Thr Pro Pro Tyr Asn Ala Gly Gly Leu Thr Gly Thr Pro Ser Pro35 40 45Ala Arg Thr Phe His Thr Thr Arg Val Cys Ser Thr Thr Phe Asn Val50 55 60Gln Asp Gly Pro Asp Phe Gln Asp Arg Val Val Asn Ser Glu Thr Pro65 70 75 80Val Val Val Asp Phe His Ala Gln Trp Cys Gly Pro Cys Lys Ile Leu85 90 95Gly Pro Arg Leu Glu Lys Met Val Ala Lys Gln His Gly Lys Val Val100 105 110Met Ala Lys Val Asp Ile Asp Asp His Thr Asp Leu Ala Ile Glu Tyr115 120 125Glu Val Ser Ala Val Pro Thr Val Leu Ala Ile Lys Asn Gly Asp Val130 135 140Val Asp Lys Phe Val Gly Ile Lys Asp Glu Asp Gln Leu Glu Ala Phe145 150 155 160Leu Lys Lys Leu Ile Gly165210161211104212PRT213Ovis aries400161Val Lys Gln Ile Glu Ser Lys Tyr Ala Phe Gln Glu Ala Leu Asn Ser1 5 10 15Ala Gly Glu Lys Leu Val Val Val Asp Phe Ser Ala Thr Trp Cys Gly20 25 30Pro Cys Lys Met Ile Lys Pro Phe Phe His Ser Leu Ser Glu Lys Tyr35 40 45Ser Asn Val Val Phe Leu Glu Val Asp Val Asp Asp Cys Gln Asp Val50 55 60Ala Ala Glu Cys Glu Val Lys Cys Met Pro Thr Phe Gln Phe Phe Lys65 70 75 80Lys Gly Gln Lys Val Ser Glu Phe Ser Gly Ala Asn Lys Glu Lys Leu85 90 95Glu Ala Thr Ile Asn Glu Leu Ile100210162211261212PRT213鼠耳芥400162Met Ala Arg Leu Val Phe Ser Leu Asn Leu Pro Ser Ser His Gly Phe1 5 10 15Asn Leu Ser Pro Arg Asn Leu Gln Ser Phe Phe Val Thr Gln Thr Gly20 25 30Ala Pro Arg Phe Arg Ala Val Arg Cys Lys Pro Asn Pro Glu Ser Ser35 40 45Glu Thr Lys Gln Glu Lys Leu Val Ile Asp Asn Gly Glu Thr Ser Ser50 55 60Ala Ser Lys Glu Val Glu Ser Ser Ser Ser Val Ala Asp Ser Ser Ser65 70 75 80Ser Ser Ser Ser Gly Phe Pro Glu Ser Pro Asn Lys Asp Ile Asn Arg85 90 95Arg Val Ala Ala Val Thr Val Ile Ala Ala Leu Ser Leu Phe Val Ser100 105 110Thr Arg Leu Asp Phe Gly Ile Ser Leu Lys Asp Leu Thr Ala Ser Ala115 120 125Leu Pro Tyr Glu Glu Ala Leu Ser Asn Gly Lys Pro Thr Val Val Glu130 135 140Phe Tyr Ala Asp Trp Cys Glu Val Cys Arg Glu Leu Ala Pro Asp Val145 150155 160Tyr Lys Ile Glu Gln Gln Tyr Lys Asp Lys Val Asn Phe Val Met Leu165 170 175Asn Val Asp Asn Thr Lys Trp Glu Gln Glu Leu Asp Glu Phe Gly Val180 185 190Glu Gly Ile Pro His Phe Ala Phe Leu Asp Arg Glu Gly Asn Glu Glu195 200 205Gly Asn Val Val Gly Arg Leu Pro Arg Gln Tyr Leu Val Glu Asn Val210 215 220Asn Ala Leu Ala Ala Gly Lys Gln Ser Ile Pro Tyr Ala Arg Ala Val225 230 235 240Gly Gln Tyr Ser Ser Ser Glu Ser Arg Lys Val His Gln Val Thr Asp245 250 255Pro Leu Ser His Gly260210163211140212PRT213鼠耳芥400163Met Gly Ser Cys Val Ser Lys Gly Lys Gly Asp Asp Asp Ser Val His1 5 10 15Asn Val Glu Phe Ser Gly Gly Asn Val His Leu Ile Thr Thr Lys Glu20 25 30Ser Trp Asp Asp Lys Leu Ala Glu Ala Asp Arg Asp Gly Lys Ile Val35 40 45Val Ala Asn Phe Ser Ala Thr Trp Cys Gly Pro Cys Lys Ile Val Ala50 55 60Pro Phe Phe Ile Glu Leu Ser Glu Lys His Ser Ser Leu Met Phe Leu65 70 75 80Leu Val Asp Val Asp Glu Leu Ser Asp Phe Ser Ser Ser Trp Asp Ile85 90 95Lys Ala Thr Pro Thr Phe Phe Phe Leu Lys Asn Gly Gln Gln Ile Gly100 105 110Lys Leu Val Gly Ala Asn Lys Pro Glu Leu Gln Lys Lys Val Thr Ser115 120 125Ile Ile Asp Ser Val Pro Glu Ser Pro Gln Arg Pro130 135 140210164211186212PRT213鼠耳芥400164Met Ser Glu Ile Val Asn Leu Ser Ser Ser Leu Arg Ser Leu Asn Prol 5 10 15Lys Ile Ser Pro Leu Val Pro Pro Tyr Arg Gln Thr Ser Ser Ser Phe20 25 30Ser Arg Pro Arg Asn Phe Lys Tyr His Ser Phe Thr Asp Lys Ile Cys35 40 45Leu Ala Ala Glu Arg Ile Arg Ala Val Asp Ile Gln Lys Gln Asp Gly50 55 60Gly Leu Gln Glu Leu Asp Asp Ser Pro Val Ser Val Glu Leu Gly Pro65 70 75 80Ile Cys Gly Glu Ser His Phe Asp Gln Val Met Glu Asp Ala Gln Lys85 90 95Leu Gly Glu Ser Val Val Ile Val Trp Met Ala Ala Trp Cys Arg Lys100 105 110Cys Ile Tyr Leu Lys Pro Lys Leu Glu Lys Leu Ala Ala Glu Phe Tyr115 120 125Pro Arg Leu Arg Phe Tyr His Val Asp Val Asn Ala Val Pro Tyr Arg130 135 140Leu Val Ser Arg Ala Gly Val Thr Leu Trp Arg Asp Gly Gln Lys Gln145 150 155 160Ala Glu Val Ile Gly Gly His Lys Ala His Phe Val Val Asn Glu Val165 170 175Arg Glu Met Ile Glu Asn Asp Ser Ile Thr180 185210165211207212PRT213鼠耳芥400165Met Glu Asn Met Ser Asn Leu Thr Ser Lys Phe Leu Leu Asn Pro Leu1 5 10 15Asn Val His Lys His Cys Ala Val Ser Asp Glu Asn Gly Asp Arg Lys20 25 30Ser His Val Leu Lys Gln Val Cys Ser Cys Ile Cys Cys Cys Asn Arg35 40 45Arg Asn Lys Thr Gln Ala Arg Ser Gln Lys Gly Ser Tyr Phe Ile Lys50 55 60Gly Lys Val His Pro Val Ser Arg Met Glu Lys Trp Glu Glu Lys Ile65 70 75 80Thr Glu Ala Asn Ser His Gly Lys Ile Ile Ala Arg His Asp Leu Ile85 90 95Leu Cys Asn Met Glu Gln Leu Val Val Asn Phe Lys Ala Ser Trp Cys100 105 110Leu Pro Ser Lys Thr Ile Leu Pro Ile Tyr Gln Glu Leu Ala Ser Thr115 120 125Tyr Thr Ser Met Ile Phe Val Thr Ile Asp Val Glu Glu Leu Ala Ile130 135 140Ser Lys Leu Ser Asp Leu Gly Val Lys Ile Cys Leu Ile Gln Glu Phe145 150 155 160Ser His Glu Trp Asn Val Asp Ala Thr Pro Thr Val Val Phe Leu Lys165 170 175Asp Gly Arg Gln Met Asp Lys Leu Val Gly Gly Asp Ala Ala Glu Leu180 185 190Gln Lys Lys Thr Ala Ala Ala Ala Asn Leu Leu Leu Arg Gln Ser195 200 205210166211175212PRT213鼠耳芥400166Met Leu Ile Pro His Ala Val Ser Phe Ala Phe Thr Tyr Leu Arg Asn1 5 10 15Ser Ala Asn Pro Asp Gln Asn Arg Glu Val Ile Ser Ile His Ser Thr20 25 30Ser Glu Leu Glu Ala Lys Thr Lys Ala Ala Lys Lys Ala Ser Arg Leu35 40 45Leu Ile Leu Tyr Phe Thr Ala Thr Trp Cys Gly Pro Cys Arg Tyr Met50 55 60Ser Pro Leu Tyr Ser Asn Leu Ala Thr Gln His Ser Arg Val Val Phe65 70 75 80Leu Lys Val Asp Ile Asp Lys Ala Asn Asp Val Ala Ala Ser Trp Asn85 90 95Ile Ser Ser Val Pro Thr Phe Cys Phe Ile Arg Asp Gly Lys Glu Val100 105 110Asp Lys Val Val Gly Ala Asp Lys Gly Ser Leu Glu Gln Lys Ile Ala115 120 125Gln His Ser Ser Ser Lys Ala Arg Tyr Ile Pro Val Phe Ile Lys Tyr130 135 140His Ser Asp Leu Leu Leu Leu Val Asn Glu Glu Thr Pro Thr Ser Asn145 150 155 160Gln Lys Leu Lys Thr Lys Thr Gly Asp Trp Phe His Ile Asn Leu165 170 175210167211132212PRT213鼠耳芥400167Met Arg Lys Gln Glu Ser Glu Gly Ala Asn Leu Glu Phe Glu Ser Lys1 5 10 15Ser Asn Asp Asn Gly Asn Val Lys Ile Ala Pro Asn Asp Gln Ser Phe20 25 30Leu Thr Ile Leu Asp Asp Ile Lys Ser Ser Lys Ser Pro Ala Val Ile35 40 45Asn Tyr Gly Ala Ser Trp Tyr Thr Leu Phe Ser Val Phe Thr Ile Thr50 55 60Leu Phe Met Leu Ile Lys Cys Ser Met Lys Cys Leu Asn Glu Asn Gly65 70 75 80Phe Val Leu Lys Leu Ser Asp Ile Asp Glu Cys Pro Glu Thr Thr Arg85 90 95His Ile Arg Tyr Thr Pro Thr Phe Gln Phe Tyr Arg Asp Gly Glu Lys100 105 110Val Asp Glu Met Phe Gly Ala Gly Glu Gln Arg Leu His Asp Arg Leu115 120 125Trp Leu His Ser130210168211151212PRT213鼠耳芥400168Met Ala Ser Ile Ser Leu Ser Ser Ser Thr Val Pro Ser Leu Asn Ser1 5 10 15Lys Glu Ser Ser Gly Val Ser Ala Phe Ala Ser Arg Ser Ile Ser Ala20 25 30Val Lys Phe Gln Phe Pro Val Arg Arg Ile Glu Ala Lys Lys Gln Thr35 40 45Phe Asp Ser Phe Glu Asp Leu Leu Val Asn Ser Asp Lys Pro Val Leu50 55 60Val Asp Tyr Tyr Ala Thr Trp Cys Gly Pro Cys Gln Phe Met Val Pro65 70 75 80Ile Leu Asn Glu Val Ser Glu Thr Leu Lys Asp Lys Ile Gln Val Val
85 90 95Lys Ile Asp Thr Glu Lys Tyr Pro Ser Ile Ala Asn Lys Tyr Lys Ile100 105 110Glu Ala Leu Pro Thr Phe Ile Leu Phe Lys Asp Gly Glu Pro Cys Asp115 120 125Arg Phe Glu Gly Ala Leu Thr Ala Lys Gln Leu Ile Gln Arg Ile Glu130 135 140Asp Ser Leu Lys Val Lys Pro145150210169211236212PRT213鼠耳芥400169Met Ala Gly Val Val Arg Leu Thr Thr Thr Ser Val Gln Ala Ile Arg1 5 10 15Val Ser Ser Ser Phe Ser Ser Phe Ala Thr Ala Leu Asn Pro Leu Gln20 25 30Pro Cys Leu Pro Pro Asn Ser Asn Leu Asn Ser Asp Lys Arg Leu Arg35 40 45Leu Leu Ser Ser Ser Pro Ser Cys Ser Ser Ser His Tyr His Pro Ser50 55 60Ser Gly Leu Gly Ser His Leu Pro Leu Arg Arg Pro Lys Ser Gln Val65 70 75 80Val Arg Val Lys Val Asp Glu Asn Val Ala Glu Thr Glu Pro Pro Lys85 90 95Trp Trp Glu Arg Asn Ala Pro Asn Met Val Asp Ile His Ser Thr Glu100 105 110Glu Phe Leu Ser Ala Leu Ser Gly Ala Gly Glu Arg Leu Val Ile Val115 120 125Glu Phe Tyr Gly Thr Trp Cys Ala Ser Cys Arg Ala Leu Phe Pro Lys130 135 140Leu Cys Lys Thr Ala Val Glu His Pro Asp Ile Val Phe Leu Lys Val145 150 155 160Asn Phe Asp Glu Asn Lys Pro Met Cys Lys Ser Leu Asn Val Arg Val165 170 175Leu Pro Phe Phe His Phe Tyr Arg Gly Ala Asp Gly Gln Leu Glu Ser180 185 190Phe Ser Cys Ser Leu Ala Lys Val Lys Lys Ala Ile Ser Val Ser Pro195 200 205Phe Pro Gln Leu Glu Leu Gly Ile Thr Leu Gln Thr Lys Arg Thr Thr210 215 220Ser Leu Phe Phe Phe Asp Arg Ile Tyr Gln Ile Leu225 230235210170211131212PRT213球莖大麥400170Met Gly Gly Cys Val Gly Lys Asp Arg Ser Ile Val Glu Asp Lys Leu1 5 10 15Asp Phe Lys Gly Gly Asn Val His Val Ile Thr Thr Lys Glu Asp Trp20 25 30Asp Gln Lys Val Ala Glu Ala Asn Lys Asp Gly Lys Ile Val Val Ala35 40 45Asn Phe Ser Ala Ser Trp Cys Gly Pro Cys Arg Val Ile Ala Pro Val50 55 60Tyr Ala Glu Met Ser Lys Thr Tyr Pro Gln Leu Met Phe Leu Thr Ile65 70 75 80Asp Val Asp Asp Leu Met Asp Phe Gly Ser Thr Trp Asp Ile Arg Ala85 90 95Thr Pro Thr Phe Phe Phe Leu Lys Asn Gly Gln Gln Ile Asp Lys Leu100 105 1l0Val Gly Ala Asn Lys Pro Glu Leu Glu Lys Lys Val Gln Ala Leu Gly115 120 125Asp Gly Ser130210171211131212PRT213黑麥草(Lolium perenne)400171Met Gly Gly Cys Val Gly Lys Asp Arg Ser Ile Val Glu Asp Lys Leu1 5 10 15Asp Phe Lys Gly Gly Asn Val His Val Ile Thr Thr Lys Glu Asp Trp20 25 30Asp Gln Lys Val Ala Glu Ala Asn Lys Asp Gly Lys Ile Val Val Ala35 40 45Asn Phe Ser Ala Ser Trp Cys Gly Pro Cys Arg Val Ile Ala Pro Val50 55 60Tyr Ala Glu Met Ser Lys Thr Tyr Pro Gln Leu Met Phe Leu Thr Ile65 70 75 80Asp Val Asp Asp Leu Met Asp Phe Ser Ser Thr Trp Asp Ile Arg Ala85 90 95Thr Pro Thr Phe Phe Phe Leu Lys Asn Gly Gln Leu Ile Asp Lys Leu100 105 110Val Gly Ala Asn Arg Pro Glu Leu Glu Lys Lys Val Gln Ala Ile Gly115 120 125Asp Gly Ser130210172211131212PRT213稻400172Met Gly Ser Cys Val Gly Lys Glu Arg Ser Asp Glu Glu Asp Lys Ile1 5 10 15Asp Phe Lys Gly Gly Asn Val His Val Ile Ser Asn Lys Glu Asn Trp20 25 30Asp His Lys Ile Ala Glu Ala Asn Lys Asp Gly Lys Ile Val Ile Ala35 40 45Asn Phe Ser Ala Ala Trp Cys Gly Pro Cys Arg Val Ile Ala Pro Val50 55 60Tyr Ala Glu Met Ser Gln Thr Tyr Pro Gln Phe Met Phe Leu Thr Ile65 70 75 80Asp Val Asp Glu Leu Met Asp Phe Ser Ser Ser Trp Asp Ile Arg Ala85 90 95Thr Pro Thr Phe Phe Phe Leu Lys Asn Gly Glu Gln Val Asp Lys Leu100 105 110Val Gly Ala Asn Lys Pro Glu Leu Glu Lys Lys Val Ala Ala Leu Ala115 120 125Asp Ser Ala130210173211296212PRT213馬鈴薯(Solanum tuberosum)400173Met Ala Thr Leu Thr Asn Phe Leu Leu Lys Pro Ser Pro Asn Leu Ala1 5 10 15Ser Ile Thr Lys Ile Ser Pro Ser Leu Tyr Ser Asn Phe Pro Phe Glu20 25 30Lys Ser Lys Gln Ser Ile Phe Lys Asn Leu Lys Thr Asn Lys Pro Leu35 40 45Leu Ile Thr Lys Ala Thr Ala Ala Pro Asp Val Glu Lys Lys Val Ala50 55 60Lys Ser Glu Arg Val Gln Lys Val Asn Ser Met Glu Glu Leu Asp Glu65 70 75 80Ala Leu Lys Lys Ala Lys Asn Arg Leu Val Val Val Glu Phe Ala Gly85 90 95Lys Asp Ser Glu Arg Ser Lys Asn Ile Tyr Pro Phe Met Val Asn Leu100 105 110Ser Lys Thr Cys Asn Asp Val Asp Phe Leu Leu Val Ile Gly Asp Glu115 120 125Thr Glu Lys Thr Lys Ala Leu Cys Arg Arg Glu Lys Ile Asp Lys Val130 135 140Pro His Phe Asn Phe Tyr Lys Ser Met Glu Lys Ile His Glu Glu Glu145 150 155 160Gly Ile Gly Pro Asp Leu Leu Ala Gly Asp Val Leu Tyr Tyr Gly Asp165 170 175Ser His Ser Glu Val Val Gln Leu His Ser Arg Glu Asp Val Glu Lys180 185 190Val Ile Gln Asp His Lys Ile Asp Lys Lys Leu Ile Val Leu Asp Val195 200 205Gly Leu Lys His Cys Gly Pro Cys Val Lys Val Tyr Pro Thr Val Ile210 215 220Lys Leu Ser Lys Gln Met Ala Asp Thr Val Val Phe Ala Arg Met Asn225 230 235 240Gly Asp Glu Asn Asp Ser Cys Met Gln Phe Leu Lys Asp Met Asp Val245 250 255Ile Glu Val Pro Thr Phe Leu Phe Ile Arg Asp Gly Glu Ile Cys Gly260 265 270Arg Tyr Val Gly Ser Gly Lys Gly Glu Leu Ile Gly Glu Ile Leu Arg275 280 285Tyr Gln Gly Val Arg Val Thr Tyr290 295210174211131212PRT213黑麥400174Met Gly Gly Cys Val Gly Lys Gly Arg Ser Ile Val Glu Glu Lys Leu1 5 10 15Asp Phe Lys Gly Gly Asn Val His Val Ile Thr Thr Lys Glu Asp Trp20 25 30Asp Gln Lys Ile Glu Glu Ala Asn Lys Asp Gly Lys Ile Val Val Ala35 40 45Asn Phe Ser Ala Ser Trp Cys Gly Pro Cys Arg Val Val Ala Pro Val50 55 60Tyr Ala Gly Met Ser Lys Thr Tyr Pro Gln Leu Met Phe Leu Thr Ile65 70 75 80Asp Val Asp Asp Leu Met Asp Phe Ser Ser Thr Trp Asp Ile Arg Ala85 90 95Thr Pro Thr Phe Phe Phe Leu Lys Asn Gly Gln Gln Ile Asp Lys Leu100 105 110Val Gly Ala Asn Lys Pro Glu Leu Glu Lys Lys Val Gln Ala Leu Gly115 120 125Asp Gly Ser130210175211119212PRT213黑麥400175Met Gly Gly Cys Val Gly Lys Gly Arg Ser Ile Val Glu Glu Lys Leu1 5 10 15Asp Phe Lys Gly Gly Asn Val His Val Ile Thr Thr Lys Glu Asp Trp20 25 30Asp Gln Lys Ile Glu Glu Ala Asn Lys Asp Gly Lys Ile Val Val Ala35 40 45Asn Phe Ser Ala Ser Trp Cys Gly Pro Cys Arg Val Ile Ala Pro Val50 55 60Tyr Ala Glu Met Ser Lys Thr Tyr Pro Gln Leu Met Phe Leu Thr Ile65 70 75 80Asp Val Asp Asp Leu Met Asp Phe Ser Ser Thr Trp Asp Ile Arg Ala85 90 95Thr Pro Thr Phe Phe Phe Leu Lys Asn Gly Gln Gln Ile Asp Lys Leu100 105 110Val Gly Ala Asn Lys Pro Glu115210176211106212PRT213Manduca sexta400176Met Ser Ile His Ile Lys Asp Ala Asp Asp Leu Lys Asn Arg Leu Ala1 5 10 15Glu Ala Gly Asp Lys Leu Val Val Ile Asp Phe Met Ala Thr Trp Cys20 25 30Gly Pro Cys Lys Met Ile Gly Pro Lys Leu Asp Glu Met Ala Ala Glu35 40 45Met Ala Asp Ser Ile Val Val Val Lys Val Asp Val Asp Glu Cys Glu50 55 60Asp Ile Ala Ala Asp Tyr Asn Ile Asn Ser Met Pro Thr Phe Val Phe65 70 75 80Val Lys Asn Ser Lys Lys Leu Glu Glu Phe Ser Gly Ala Asn Val Asp85 90 95Lys Leu Lys Asn Thr Ile Leu Lys Leu Lys100 105210177211221212PRT213大豆慢生根瘤菌400177Met Leu Asp Thr Lys Pro Ser Ala Thr Arg Arg Ile Pro Leu Val Ile1 5 10 15Ala Thr Val Ala Val Gly Gly Leu Ala Gly Phe Ala Ala Leu Tyr Gly20 25 30Leu Gly Leu Ser Arg Ala Pro Thr Gly Asp Pro Ala Cys Arg Ala Ala35 40 45Val Ala Thr Ala Gln Lys Ile Ala Pro Leu Ala His Gly Glu Val Ala50 55 60Ala Leu Thr Met Ala Ser Ala Pro Leu Lys Leu Pro Asp Leu Ala Phe65 70 75 80Glu Asp Ala Asp Gly Lys Pro Lys Lys Leu Ser Asp Phe Arg Gly Lys85 90 95Thr Leu Leu Val Asn Leu Trp Ala Thr Trp Cys Val Pro Cys Arg Lys100 105 110Glu Met Pro Ala Leu Asp Glu Leu Gln Gly Lys Leu Ser Gly Pro Asn115 120 125Phe Glu Val Val Ala Ile Asn Ile Asp Thr Arg Asp Pro Glu Lys Pro
130 135 140Lys Thr Phe Leu Lys Glu Ala Asn Leu Thr Arg Leu Gly Tyr Phe Asn145 150 155 160Asp Gln Lys Ala Lys Val Phe Gln Asp Leu Lys Ala Ile Gly Arg Ala165 170 175Leu Gly Met Pro Thr Ser Val Leu Val Asp Pro Gln Gly Cys Glu Ile180 185 190Ala Thr Ile Ala Gly Pro Ala Glu Trp Ala Ser Glu Asp Ala Leu Lys195 200 205Leu Ile Arg Ala Ala Thr Gly Lys Ala Ala Ala Ala Leu210 215 220210178211167212PRT213流感嗜血桿菌400178Met Lys Ile Lys Lys Leu Leu Lys Asn Gly Leu Ser Leu Phe Leu Thr1 5 10 15Phe Ile Val Ile Thr Ser Ile Leu Asp Phe Val Arg Arg Pro Val Val20 25 30Pro Glu Glu Ile Asn Lys Ile Thr Leu Gln Asp Leu Gln Gly Asn Thr35 40 45Phe Ser Leu Glu Ser Leu Asp Gln Asn Lys Pro Thr Leu Leu Tyr Phe50 55 60Trp Gly Thr Trp Cys Gly Tyr Cys Arg Tyr Thr Ser Pro Ala Ile Asn65 70 75 80Ser Leu Ala Lys Glu Gly Tyr Gln Val Val Ser Val Ala Leu Arg Ser85 90 95Gly Asn Glu Ala Asp Val Asn Asp Tyr Leu Ser Lys Asn Asp Tyr His100 105 110Phe Thr Thr Val Asn Asp Pro Lys Gly Glu Phe Ala Glu Arg Trp Gln115 120 125Ile Asn Val Thr Pro Thr Ile Val Leu Leu Ser Lys Gly Lys Met Asp130 135 140Leu Val Thr Thr Gly Leu Thr Ser Tyr Trp Gly Leu Lys Val Arg Leu145 150 155 160Phe Phe Ala Glu Phe Phe Gly165210179211163212PRT213Leishmania major400179Met Leu Lys Val Ser Ser Lys Glu His Tyr Ala Glu Ile Lys Lys Lys1 5 10 15Ala Glu Asp Ser Leu Gly Leu Val Val His Phe Ser Ala Thr Trp Cys20 25 30Glu Pro Cys Thr Ala Val Asn Glu His Leu Thr Lys Gln Ala Ala Glu35 40 45Tyr Gly Asp Asn Val Val Phe Ala Glu Val Asp Cys Gly Glu Leu Gly50 55 60Asp Val Cys Glu Ala Glu Gly Val Glu Ser Val Pro Phe Val Ala Tyr65 70 75 80Phe Arg Thr Pro Leu Val Gly Asp Asp Arg Arg Val Glu Arg Val Ala85 90 95Asp Val Ala Gly Ala Lys Phe Asp Gln Ile Asp Met Asn Thr His Ser100 105 110Leu Phe Gly Glu Lys Gly Gly Asn Arg Gly Ser Ala Glu Gly Leu Cys115 120 125His Ser Gly Arg Leu Pro Ala Leu Pro His Glu Ala Ala Arg Gly Arg130 135 140Asn Val His His Arg His Pro Ile Ser Ser Ala Leu Arg Leu Tyr Trp145 150 155 160Ser Ala Val210180211275212PRT213高山被孢黴400180Met Val Ser Asn Asn Tyr Ile Asp Ile Thr Ser Glu Asp Asp Phe Ala1 5 10 15Gln Val Phe Gln Pro Ser Ser Ser Thr Val Tyr Ala Leu Asn Phe Trp20 25 30Ala Ala Trp Ala Pro Pro Cys Val Gln Met Asn Glu Val Phe Glu Glu35 40 45Leu Ala Ala Lys Asn Ala Asn Val Asn Phe Leu Lys Ile Glu Ala Glu50 55 60Lys Phe Pro Asp Ile Ser Glu Asp Tyr Glu Ile Ala Ala Val Pro Ser65 70 75 80Phe Val Ile Val Lys Glu Gly Thr Val Val Asp Arg Val Glu Gly Ala85 90 95Asn Ala Pro Glu Leu Ala Lys Val Ile Ala Lys Tyr Ser Lys Ser Thr100 105 110Ser Ser Pro Leu Pro Thr Gln Ser Ser Thr Met Ala Ala Ala Gly His115 120 125Ala Ala Pro Ser Val Ala Pro Pro Thr Met Ser Pro Glu Glu Met Asn130 135 140Ala Arg Leu Lys Glu Leu Thr Ser Ser Ser Ser Val Met Ala Phe Ile145 150 155 160Lys Gly Thr Pro Thr Ala Pro Arg Cys Gln Phe Ser Arg Gln Leu Leu165 170 175Glu Ile Leu Thr Ala Gln Asn Ile Arg Phe Ser Ser Phe Asn Ile Leu180 185 190Ala Asp Asp Glu Val Arg Gln Ala Met Lys Thr Phe Ser Asp Trp Pro195 200 205Thr Phe Pro Gln Val Tyr Val Lys Gly Glu Phe Val Gly Gly Leu Asp210 215220Val Val Lys Glu Leu Val Ala Ser Gly Glu Phe Gln Ala Leu Val Pro225 230 235 240Ala Glu Lys Asp Leu Lys Thr Arg Met Asp Glu Leu Ile Arg Lys Ala245 250 255Pro Val Met Ile Phe Ile Lys Gly Ser Pro Glu Thr Pro Arg Cys Gly260 265 270Phe Ser Lys275210181211160212PRT213淋病奈瑟氏球菌400181Met Lys Arg Leu Ile Leu Ala Ala Ile Ala Leu Ala Ala Thr Phe Gly1 5 10 15Ala His Thr Ala Ser Gly Asp Glu Leu Ala Gly Trp Lys Asp Asn Thr20 25 30Pro Gln Asn Leu Gln Ser Leu Lys Ala Pro Val Arg Ile Ala Asn Leu35 40 45Trp Ala Thr Trp Cys Gly Pro Cys Arg Lys Glu Met Pro Ala Met Ser50 55 60Lys Trp Tyr Lys Ala Gln Lys Lys Gly Ser Val Asp Met Val Gly Ile65 70 75 80Ala Leu Asp Thr Ser Asp Asn Ile Gly Asn Phe Leu Lys Gln Thr Pro
85 90 95Val Ser Tyr Pro Ile Trp Arg Tyr Thr Gly Ala Asn Ser Arg Ser Phe100 105 110Met Lys Ser Tyr Gly Asn Asn Val Gly Val Leu Pro Phe Thr Val Val115 120 125Glu Ala Pro Lys Cys Gly Tyr Arg Gln Thr Ile Thr Gly Glu Leu Asn130 135 140Glu Lys Ser Leu Thr Glu Ala Val Lys Leu Ala His Ser Lys Cys Arg145 150 155 160210182211208212PRT213百脈根瘤菌400182Met Ala Gly Ala Leu Ala Gly Ala Val Ala Val Tyr Val Ser Glu Ser1 5 10 15Arg Ser Gly Asn Asn Ala Pro Ala Arg Val Ala Val Gly Gly Ser Lys20 25 30Asp Asp Val Ala Cys Ala Ala Lys Ser Gly Arg Ala Lys Lys Ile Ala35 40 45Ala Ala Ala Thr Gly Glu Val AlaAla Leu Leu Pro AlaAsp Pro Pro50 55 60Gln Ser Met Lys Ser Leu Ala PheAsn Gly Pro Asp Gly Lys Pro Met65 70 75 80Thr Ile Ala Asp His Ala Gly Lys Thr Val Leu Leu Asn Leu Trp Ala85 90 95Thr Trp Cys Ala Pro Cys Arg Ala Glu Met Pro Ala Leu Asn Ala Leu100 105 110Gln Lys Asp Lys Gly Ser Asp Ala Phe Gln Val Ile Ala Val Asn Val115 120 125Asp Ala Gly Asp Asp Val Lys Pro Lys Lys Phe Leu Lys Glu Thr Gly130 135 140Val Glu Ala Leu Gly Tyr Phe Arg Asp Ser Thr Val Ala Leu Phe Asn145 150 155 160Asp Leu Lys Ala Arg Gly Leu Ala Leu Gly Leu Pro Val Thr Met Leu165 170 175Ile Asp Ser Glu Gly Cys Leu Ile Ala His Met Asn Gly Pro Ala Glu180 185 190Trp Ser Gly Arg Asp Ala Arg Arg Leu Val Glu Thr Ala Leu Gly Ser195 200 205210183211176212PRT213莢膜紅細菌400183Met Ala Lys Pro Leu Met Phe Leu Pro Leu Leu Val Met Ala Gly Phe1 5 10 15Val Gly Ala Gly Tyr Phe Ala Met Gln Gln Asn Asp Pro Asn Ala Met20 25 30Pro Thr Ala Leu Ala Gly Lys Glu Ala Pro Ala Val Arg Leu Glu Pro35 40 45Leu Gly Ala Glu Ala Pro Phe Thr Asp Ala Asp Leu Arg Asp Gly Lys50 55 60Ile Lys Leu Val Asn Phe Trp Ala Ser Trp Cys Ala Pro Cys Arg Val65 70 75 80Glu His Pro Asn Leu Ile Gly Leu Lys Gln Asp Gly Ile Glu Ile Met85 90 95Gly Val Asn Trp Lys Asp Thr Pro Asp Gln Ala Gln Gly Phe Leu Ala100 105 110Glu Met Gly Ser Pro Tyr Thr Arg Leu Gly Ala Asp Pro Gly Asn Lys115 120 125Met Gly Leu Asp Trp Gly Val Ala Gly Val Pro Glu Thr Phe Val Val130 135 140Asp Gly Ala Gly Arg Ile Leu Thr Arg Ile Ala Gly Pro Leu Thr Glu145 150 155 160Asp Val Ile Thr Lys Lys Ile Asp Pro Leu Leu Ala Gly Thr Ala Asp165 170 175210184211105212PRT213集胞籃細菌屬400184Met Ala Val Lys Lys Gln Phe Ala Asn Phe Ala Glu Met Leu Ala Gly1 5 10 15Ser Pro Lys Pro Val Leu Val Asp Phe Tyr Ala Thr Trp Cys Gly Pro20 25 30Cys Gln Met Met Ala Pro Ile Leu Glu Gln Val Gly Ser His Leu Arg35 40 45Gln Gln Ile Gln Val Val Lys Ile Asp Thr Asp Lys Tyr Pro Ala Ile50 55 60Ala Thr Gln Tyr Gln Ile Gln Ser Leu Pro Thr Leu Val Leu Phe Lys65 70 75 80Gln Gly Gln Pro Val His Arg Met Glu Gly Val Gln Gln Ala Ala Gln85 90 95Leu Ile Gln Gln Leu Gln Val Phe Val100 105210185211109212PRT213集胞籃細菌屬400185Met Ser Leu Leu Glu Ile Thr Asp Ala Glu Phe Glu Gln Glu Thr Gln1 5 10 15Gly Gln Thr Lys Pro Val Leu Val Tyr Phe Trp Ala Ser Trp Cys Gly20 25 30Pro Cys Arg Leu Met Ala Pro Ala Ile Gln Ala Ile Ala Lys Asp Tyr35 40 45Gly Asp Lys Leu Lys Val Leu Lys Leu Glu Val Asp Pro Asn Pro Ala50 55 60Ala Val Ala Gln Cys Lys Val Glu Gly Val Pro Ala Leu Arg Leu Phe65 70 75 80Lys Asn Asn Glu Leu Val Met Thr His Glu Gly Ala Ile Ala Lys Pro85 90 95Lys Leu Leu Glu Leu Leu Lys Glu Glu Leu Asp Phe Ile100 105210186211290212PRT213粟酒裂殖糖酵母400186Met Ser Val Ile Glu Ile Arg Ser Tyr Gln His Trp Ile Ser Thr Ile1 5 10 15Pro Lys Ser Gly Tyr Leu Ala Val Asp Cys Tyr Ala Asp Trp Cys Gly20 25 30Pro Cys Lys Ala Ile Ser Pro Leu Phe Ser Gln Leu Ala Ser Lys Tyr35 40 45Ala Ser Pro Lys Phe Val Phe Ala Lys Val Asn Val Asp Glu Gln Arg50 55 60Gln Ile Ala Ser Gly Leu Gly Val Lys Ala Met Pro Thr Phe Val Phe65 70 75 80Phe Glu Asn Gly Lys Gln Ile Asp Met Leu Thr Gly Ala Asn Pro Gln85 90 95Ala Leu Lys Glu Lys Val Ala Leu Ile Ser Ser Lys Ala Thr Gly Thr100 105 110Gly Ala Leu Ala Ser Ser Ser Ser Ala Pro Val Lys Gly Phe Ala Ser115 120 125Leu Gln Gly Cys Ile Glu Asn Pro Gln Leu Glu Cys Leu Asn Gln Gln130135 140Asp Asp His Asp Leu Lys Ser Ala Phe Asn Ser Asn Pro Ser Ser Phe145 150 155 160Leu Glu Ser Asp Val Asp Glu Gln Leu Met Ile Tyr Ile Pro Phe Leu165 170 175Glu Val Val Lys Val His Ser Ile Ala Ile Thr Pro Val Lys Gly Glu180 185 190Thr Ser Ser Ala Pro Lys Thr Ile Lys Leu Tyr Ile Asn Gln Pro Asn195 200 205Asn Leu Ser Phe Glu Asp Ala Glu Ser Phe Thr Pro Thr Gln Val Ile210 215 220Glu Asp Ile Val Tyr Glu Gln Asp Asp Gln Pro Thr Ile Ile Pro Leu225 230 235 240Arg Phe Val Lys Phe Gln Arg Val Asn Ser Leu Val Ile Phe Ile Tyr245 250 255Ser Asn Val Gly Glu Glu Glu Thr Thr Lys Ile Ser Arg Leu Glu Leu260 265 270Phe Gly Glu Pro Val Gly Asp Ser Ser Lys Gly Lys Leu Gln Lys Val275 280 285Glu Ala290210187211185212PRT213蒼白密螺旋體400187Met Phe Arg Ser Asp Leu Val Leu Ala Val Trp Gly Val Thr Cys Val1 5 10 15Gln Ala Ala Asp Val Ala His Asn Ala Asp Val Pro Ser Arg Ser Leu20 25 30Lys Ala Leu Glu Arg Phe Arg Phe Phe Val Tyr Pro Lys Pro Leu Asp35 40 45Leu Ser Ser Asp Phe His Ala Lys Ala Leu Lys Gly Glu Ala Leu Val50 55 60Pro Ser Leu Phe Lys Gly Lys Val Thr Leu Leu Asn Phe Trp Ala Thr65 70 75 80Trp Cys Pro Pro Cys Arg A la Glu Met Pro Ser Met Asp Arg Met Gln85 90 95Ala Leu Met Arg Gly Asn Asp Phe Gln Ile Val Ala Val Asn Val Gly100 105 110Asp Ser Arg Lys Gln Val Glu Ser Phe Ile Ala Arg Gly Lys His Thr115 120 125Phe Pro Ile Tyr Leu Asp Glu Glu Gly Ser Leu Gly Ser Val Phe Ala130 135 140Ser Arg Gly Leu Pro Thr Thr Tyr Val Val Asp Lys Ala Gly Arg Ile145 150 155 160Val Ala Val Val Val Gly Ser Val Glu Tyr Asp Gln Pro Glu Leu Val165 170 175Ala Leu Phe Lys Glu Leu Ala Arg Asp180 185210188211246212PRT213Caenorhabditis elegans400188Met Leu Leu Arg Leu Leu Ala Val Leu Gly Leu Phe Ala Val Gly Val1 5 10 15Ser Gly Gly Pro Thr Arg Ser Ser Lys Leu Val Phe Leu Asn Glu Glu20 25 30Asn Trp Thr Asp Leu Met Lys Gly Glu Trp Met Ile Glu Phe His Ala35 40 45Pro Trp Cys Pro Ala Cys Lys Asp Leu Gln Lys Ala Trp Asn Ala Phe50 55 60Ala Asp Trp Ser Asp Asp Leu Gly Ile Lys Val Gly Glu Val Asp Val65 70 75 80Thr Val Asn Pro Gly Leu Ser Gly Arg Phe Leu Val Thr Ala Leu Pro85 90 95Thr Ile Tyr His Val Lys Asp Gly Val Phe Arg Gln Tyr Ser Gly Ala100 105 110Arg Asp Lys Asn Asp Phe Ile Ser Phe Val Glu Asp Lys Lys Tyr Arg115 120 125Val Ile Asp Pro Val Pro Asp Tyr Lys His Pro Asn Ser Lys Gln Met130 135 140Ala Val Val Ala Val Phe Phe Lys Leu Ser Met Ser Val Arg Asp Leu145 150 155 160His Asn His Leu Val Glu Asp Lys Gly Ile Pro Ser Trp Ala Ser Tyr165 170 175Gly Leu Phe Ala Gly Val Thr Leu Ala Leu Gly Cys Val Leu Gly Phe180 185 190Phe Ile Val Ile Ile Ile Asp Gln Val Phe Pro Thr Gly Pro Arg Lys195 200 205Ser Gln Gln Ala Lys Lys Thr Glu Lys Lys Asp Ala Lys Lys Asp Ser210 215 220Gly Thr Glu Ser Pro Thr Lys Lys Asn Gly Asn Asn Asn Asn Gly Lys225 230 235 240Glu Thr Lys Lys Thr Lys245210189211284212PRT213Caenorhabditis elegans400189Met Pro Val Ile Asn Val Lys Asp Asp Glu Asp Phe Arg Asn Gln Leu1 5 10 15Ser Leu Ala Gly Leu Lys Ser Val Ile Val Asp Phe Thr Ala Val Trp20 25 30Cys Gly Pro Cys Lys Met Ile Ala Pro Thr Phe Glu Ala Leu Ser Asn35 40 45Gln Tyr Leu Gly Ala Val Phe Leu Lys Val Asp Val Glu Ile Cys Glu50 55 60Lys Thr Ser Ser Glu Asn Gly Val Asn Ser Met Pro Thr Phe Met Val65 70 75 80Phe Gln Ser Gly Val Arg Val Glu Gln Met Lys Gly A la Asp Ala Lys85 90 95Ala Leu Glu Thr Met Val Lys Lys Tyr Ala Asp Asn Ser Ala Ala Asp100 105 110Ser Leu Val Ala Gly Gln Met Asp Leu Thr Pro Leu Val Asp Lys Lys115 120 125Gln Met Glu Cys Leu Asn Glu Ser Asp Asp Thr Pro Leu Gly Arg Phe130 135 140Leu Glu Gly Asn Cys Asn Leu Val Ser Asp Cys Asp Glu Gln Leu Ile145 150 155 160Ile Ser Leu Pro Phe Asn Gln Pro Val Lys Val His Ser Ile Leu Ile165 170 175Lys Gly Val Ser Asp Arg Ala Pro Lys Lys Val Lys Val Phe Ile Asn180 185 190Leu Pro Lys Thr Thr Asp Phe Asp Asn Ala Thr Ala Leu Glu Pro Thr195 200 205Gln Met Leu Glu Phe Asp Glu Ser Ser Ile Gln Gly His Gly Gln Val210 215 220Val Ala Leu Lys Tyr Val Lys Phe Gln Asn Val Gln Asn Ile Gln Phe225 230 235240Phe Ile Glu Asn Asn Val Gly Gly Gly Asp Val Thr Glu Leu Val Lys245 250 255Leu Thr Val Phe Gly Thr Pro Leu Ser Ala Leu Asn Met Asn Glu Phe260 265 270Lys Arg Val Ala Gly Lys Ala Gly Asp Ala Ala His275 280210190211287212PRT213黃果蠅400190Met Ser Val Arg Val Ile Asn Asp Glu Ser His Phe Gln Ala Glu Leu1 5 10 15Ala Gln Ala Gly Ile Gln Leu Val Val Val Asp Phe Thr Ala Ser Trp20 25 30Cys Gly Pro Cys Lys Arg Ile Ala Pro Ile Phe Glu Thr Phe Pro Thr35 40 45Lys Tyr Pro Lys Ala Ile Phe Leu Lys Val Asp Val Asp Lys Cys Gln50 55 60Asp Thr Ala Ala Gly Gln Gly Val Ser Ala Met Pro Thr Phe Ile Phe65 70 75 80Tyr Arg Asn Arg Thr Lys Ile Asp Arg Val Gln Gly Ala Asp Val Asn85 90 95Gly Leu Glu Ala Lys Ile Gln Glu His Ile Gly Thr Ser Gly Gly Glu100 105 110Glu Gly Gly Glu Asp Tyr Gly Gln Gly Leu Met Glu Leu Asn Thr Phe115 120 125Ile Ser Lys Gln Glu Cys Glu Cys Leu Asn Glu Ala Asp Asp His Asn130 135 140Leu Lys His Ala Leu Ala Ser Ala Gly Gly Tyr Leu Gln Ser Asp Cys145 150 155 160Asp Glu Gln Leu Ile Leu Ser Ile Thr Phe Asn Gln Ala Val Lys Ile165 170 175His Ser Leu Lys Phe Lys Ala Pro Ser His Leu Gly Pro Lys Asp Val180 185 190Lys Leu Phe Ile Asn Gln Pro Arg Thr Ile Asp Phe Asp Met Ala Glu195 200 205Ser Met Asn Ser Val Gln Asp Leu Ser Leu Ala Gln Lys Glu Leu Glu210 215 220Ser Gly Val Pro Val Asn Leu Arg Tyr Val Lys Phe Gln Asn Val Gln225 230 235 240Asn Ile Gln Ile Phe Val Lys Asn Asn Gln Ser Gly Gly Asp Val Thr245 250 255Gln Ile Asp Tyr Ile Gly Phe Ile Gly Ser Pro Ile Met Thr Thr Lys260 265 270Met Asn Asp Phe Lys Arg Val Ala Gly Lys Lys Gly Glu Ser His275 280 285210191211289212PRT213人400191Met Val Gly Val Lys Pro Val Gly Ser Asp Pro Asp Phe Gln Pro Glu1 5 10 15Leu Ser Gly Ala Gly Ser Arg Leu Ala Val Val Lys Phe Thr Met Arg20 25 30Gly Cys Gly Pro Cys Leu Arg Ile Ala Pro Ala Phe Ser Ser Met Ser
35 40 45Asn Lys Tyr Pro Gln Ala Val Phe Leu Glu Val Asp Val His Gln Cys50 55 60Gln Gly Thr Ala Ala Thr Asn Asn Ile Ser Ala Thr Pro Thr Phe Leu65 70 75 80Phe Phe Arg Asn Lys Val Arg Ile Asp Gln Tyr Gln Gly Ala Asp Ala85 90 95Val Gly Leu Glu Glu Lys Ile Lys Gln His Leu Glu Asn Asp Pro Gly100 105 110Ser Asn Glu Asp Thr Asp Ile Pro Lys Gly Tyr Met Asp Leu Met Pro115 120 125Phe Ile Asn Lys Ala Gly Cys Glu Cys Leu Asn Glu Ser Asp Glu His130 135 140Gly Phe Asp Asn Cys Leu Arg Lys Asp Thr Thr Phe Leu Glu Ser Asp145 150 155 160Cys Asp Glu Gln Leu Leu Ile Thr Val Ala Phe Asn Gln Pro Val Lys165 170 175Leu Tyr Ser Met Lys Phe Gln Gly Pro Asp Asn Gly Gln Gly Pro Lys180 185 190Tyr Val Lys Ile Phe Ile Asn Leu Pro Arg Ser Met Asp Phe Glu Glu195 200 205Ala Glu Arg Ser Glu Pro Thr Gln Ala Leu Glu Leu Thr Glu Asp Asp210 215220Ile Lys Glu Asp Gly Ile Val Pro Leu Arg Tyr Val Lys Phe Gln Asn225 230 235 240Val Asn Ser Val Thr Ile Phe Val Gln Ser Asn Gln Gly Glu Glu Glu245 250 255Thr Thr Arg Ile Ser Tyr Phe Thr Phe Ile Gly Thr Pro Val Gln Ala260 265 270Thr Asn Met Asn Asp Phe Lys Arg Val Val Gly Lys Lys Gly Glu Ser275 280 285His210192211335212PRT213人400192Met Glu Ala Gly Ala Ala Glu Ala Ala Val Ala Ala Val Glu Glu Val1 5 10 15Gly Ser Ala Gly Gln Phe Glu Glu Leu Leu Arg Leu Lys Ala Lys Ser20 25 30Leu Leu Val Val His Phe Trp Ala Pro Trp Ala Pro Gln Cys Ala Gln35 40 45Met Asn Glu Val Met Ala Glu Leu Ala Lys Glu Leu Pro Gln Val Ser50 55 60Phe Val Lys Leu Glu Ala Glu Gly Val Pro Glu Val Ser Glu Lys Tyr65 70 75 80Glu Ile Ser Ser Val Pro Thr Phe Leu Phe Phe Lys Asn Ser Gln Lys85 90 95Ile Asp Arg Leu Asp Gly Ala His Ala Pro Glu Leu Thr Lys Lys Val100 105 110Gln Arg His Ala Ser Ser Gly Ser Phe Leu Pro Ser Ala Asn Glu His115 120 125Leu Lys Glu Asp Leu Asn Leu Arg Leu Lys Lys Leu Thr His Ala Ala130 135 140Pro Cys Met Leu Phe Met Lys Gly Thr Pro Gln Glu Pro Arg Cys Gly145 150 155 160Phe Ser Lys Gln Met Val Glu Ile Leu His Lys His Asn Ile Gln Phe165 170 175Ser Ser Phe Asp Ile Phe Ser Asp Glu Glu Val Arg Gln Gly Leu Lys180 185 190Ala Tyr Ser Ser Trp Pro Thr Tyr Pro Gln Leu Tyr Val Ser Gly Glu195 200 205Leu Ile Gly Gly Leu Asp Ile Ile Lys Glu Leu Glu Ala Ser Glu Glu210 215 220Leu Asp Thr Ile Cys Pro Lys Ala Pro Lys Leu Glu Glu Arg Leu Lys225 230 235 240Val Leu Thr Asn Lys Ala Ser Val Met Leu Phe Met Lys Gly Asn Lys245 250 255Gln Glu Ala Lys Cys Gly Phe Ser Lys Gln Ile Leu Glu Ile Leu Asn260 265 270Ser Thr Gly Val Glu Tyr Glu Thr Phe Asp Ile Leu Glu Asp Glu Glu275 280 285Val Arg Gln Gly Leu Lys Ala Tyr Ser Asn Trp Pro Thr Tyr Pro Gln290 295 300Leu Tyr Val Lys Gly Glu Leu Val Gly Gly Leu Asp Ile Val Lys Glu305 310 315 320Leu Lys Glu Asn Gly Glu Leu Leu Pro Ile Leu Arg Gly Glu Asn325 330 335210193211131212PRT213Phalaris coerulescens400193Met Gly Gly Cys Val Gly Lys Asp Arg Gly Ile Val Glu Asp Lys Leu1 5 10 15Asp Phe Lys Gly Gly Asn Val His Val Ile Thr Thr Lys Glu Asp Trp20 25 30Asp Gln Lys Ile Ala Glu Ala Asn Lys Asp Gly Lys Ile Val Val Ala35 40 45Asn Phe Ser Ala Ser Trp Cys Gly Pro Cys Arg Val Ile Ala Pro Val50 55 60Tyr Ala Glu Met Ser Lys Thr Tyr Pro Gln Leu Met Phe Leu Thr Ile65 70 75 80Asp Val Asp Asp Leu Val Asp Phe Ser Ser Thr Trp Asp Ile Arg Ala85 90 95Thr Pro Thr Phe Phe Phe Leu Lys Asn Gly Gln Gln Ile Asp Lys Leu100 105 110Val Gly Ala Asn Lys Pro Glu Leu Glu Lys Lys Val Gln Ala Leu Gly115 120 125Asp Gly Ser130210194211144212PRT213Trypanosoma brucei brucei400194Met Ser Gly Leu Ala Lys Tyr Leu Pro Gly Ala Thr Asn Leu Leu Ser1 5 10 15Lys Ser Gly Glu Val Ser Leu Gly Ser Leu Val Gly Lys Thr Val Phe20 25 30Leu Tyr Phe Ser Ala Ser Trp Cys Pro Pro Cys Arg Gly Phe Thr Pro35 40 45Val Leu Ala Glu Phe Tyr Glu Lys His His Val Ala Lys Asn Phe Glu50 55 60Val Val Leu Ile Ser Trp Asp Glu Asn Glu Ser Asp Phe His Asp Tyr65 70 75 80Tyr Gly Lys Met Pro Trp Leu Ala Leu Pro Phe Asp Gln Arg Ser Thr85 90 95Val Ser Glu Leu Gly Lys Thr Phe Gly Val Glu Ser Ile Pro Thr Leu100 105 110Ile Thr Ile Asn Ala Asp Thr Gly Ala Ile Ile Gly Thr Gln Ala Arg115 120 125Thr Arg Val Ile Glu Asp Pro Asp Gly Ala Asn Phe Pro Trp Pro Asn
130 135140210195211333212PRT213鼠耳芥400195Met Asn Gly Leu Glu Thr His Asn Thr Arg Leu Cys Ile Val Gly Ser1 5 10 15Gly Pro Ala Ala His Thr Ala Ala Ile Tyr Ala Ala Arg Ala Glu Leu20 25 30Lys Pro Leu Leu Phe Glu Gly Trp Met Ala Asn Asp Ile Ala Pro Gly35 40 45Gly Gln Leu Thr Thr Thr Thr Asp Val Glu Asn Phe Pro Gly Phe Pro50 55 60Glu Gly Ile Leu Gly Val Glu Leu Thr Asp Lys Phe Arg Lys Gln Ser65 70 75 80Glu Arg Phe Gly Thr Thr Ile Phe Thr Glu Thr Val Thr Lys Val Asp85 90 95Phe Ser Ser Lys Pro Phe Lys Leu Phe Thr Asp Ser Lys Ala Ile Leu100 105 110Ala Asp Ala Val Ile Leu Ala Thr Gly Ala Val Ala Lys Arg Leu Ser115 120 125Phe Val Gly Ser Gly Glu Ala Ser Gly Gly Phe Trp Asn Arg Gly Ile130 135 140Ser Ala Cys Ala Val Cys Asp Gly Ala Ala Pro Ile Phe Arg Asn Lys145 150 155 160Pro Leu Ala Val Ile Gly Gly Gly Asp Ser Ala Met Glu Glu Ala Asn165 170 175Phe Leu Thr Lys Tyr Gly Ser Lys Val Tyr Ile Ile His Arg Arg Asp180 185 190Ala Phe Arg Ala Ser Lys Ile Met Gln Gln Arg Ala Leu Ser Asn Pro195 200 205Lys Ile Asp Val Ile Trp Asn Ser Ser Val Val Glu Ala Tyr Gly Asp210 215 220Gly Glu Arg Asp Val Leu Gly Gly Leu Lys Val Lys Asn Val Val Thr225 230 235 240Gly Asp Val Ser Asp Leu Lys Val Ser Gly Leu Phe Phe Ala Ile Gly245 250 255His Glu Pro Ala Thr Lys Phe Leu Asp Gly Gly Val Glu Leu Asp Ser260 265 270Asp Gly Tyr Val Val Thr Lys Pro Gly Thr Thr Gln Thr Ser Val Pro275 280 285Gly Val Phe Ala Ala Gly Asp Val Gln Asp Lys Lys Tyr Arg Gln Ala290 295 300Ile Thr Ala Ala Gly Thr Gly Cys Met Ala Ala Leu Asp Ala Glu His305 310 315 320Tyr Leu Gln Glu Ile Gly Ser Gln Gln Gly Lys Ser Asp325 330210196211383212PRT213鼠耳芥400196Met Cys Trp Ile Ser Met Ser Gln Ser Arg Phe Ile Ile Lys Ser Leu1 5 10 15Phe Ser Thr Ala Gly Gly Phe Leu Leu Gly Ser Ala Leu Ser Asn Pro20 25 30Pro Ser Leu Ala Thr Ala Phe Ser Ser Ser Ser Ser Ser Ser Ser Ala35 40 45Ala Ala Ala Val Asp Met Glu Thr His Lys Thr Lys Val Cys Ile Val50 55 60Gly Ser Gly Pro Ala Ala His Thr Ala Ala Ile Tyr Ala Ser Arg Ala65 70 75 80Glu Leu Lys Pro Leu Leu Phe Glu Gly Trp Met Ala Asn Asp Ile Ala85 90 95Pro Gly Gly Gln Leu Thr Thr Thr Thr Asp Val Glu Asn Phe Pro Gly100 105 110Phe Pro Glu Gly Ile Leu Gly Ile Asp Ile Val Glu Lys Phe Arg Lys115 120 125Gln Ser Glu Arg Phe Gly Thr Thr Ile Phe Thr Glu Thr Val Asn Lys130 135 140Val Asp Phe Ser Ser Lys Pro Phe Lys Leu Phe Thr Asp Ser Arg Thr145 150 155 160Val Leu Ala Asp Ser Val Ile Ile Ser Thr Gly Ala Val Ala Lys Arg165 170 175Leu Ser Phe Thr Gly Ser Gly Glu Gly Asn Gly Gly Phe Trp Asn Arg180 185 190Gly Ile Ser Ala Cys Ala Val Cys Asp Gly Ala Ala Pro Ile Phe Arg195 200 205Asn Lys Pro Leu Val Val Ile Gly Gly Gly Asp Ser Ala Met Glu Glu210 215 220Ala Asn Phe Leu Thr Lys Tyr Gly Ser Lys Val Tyr Ile Ile His Arg225 230 235 240Arg Asp Thr Phe Arg Ala Ser Lys Ile Met Gln Gln Arg Ala Leu Ser245 250 255Asn Pro Lys Ile Glu Val Ile Trp Asn Ser Ala Val Val Glu Ala Tyr260 265 270Gly Asp Glu Asn Gly Arg Val Leu Gly Gly Leu Lys Val Lys Asn Val275 280 285Val Thr Gly Asp Val Ser Asp Leu Lys Val Ser Gly Leu Phe Phe Ala290 295 300Ile Gly His Glu Pro Ala Thr Lys Phe Leu Asp Gly Gln Leu Glu Leu305 310 315 320Asp Glu Asp Gly Tyr Val Val Thr Lys Pro Gly Thr Thr Lys Thr Ser325 330 335Val Val Gly Val Phe Ala Ala Gly Asp Val Gln Asp Lys Lys Tyr Arg340 345 350Gln Ala Ile Thr Ala Ala Gly Thr Gly Cys Met Ala Ala Leu Asp Ala355 360 365Glu His Tyr Leu Gln Glu Ile Gly Ser Gln Glu Gly Lys Ser Asp370 375 380210197211323212PRT213Aquifex aeolicus400197Met Ala Val Ser Leu Met Gln Gln Pro Asp Lys Val Tyr Asp Val Ile1 5 10 15Ile Ile Gly Ala Gly Pro Ala Gly Thr Thr Ala Ala Ile Tyr Thr Ala20 25 30Arg Ala Gly Trp Lys Thr Leu Val Leu Tyr Arg Ala Glu Ala Asp Gly35 40 45Ala Leu Gly Val Thr Gln Lys Ile Glu Asn Tyr Pro Gly Val Pro Gly50 55 60Pro Leu Ser Gly Tyr Glu Leu Leu Lys Ile Met Arg Glu Gln Ala Lys65 70 75 80Ser Phe Gly Ala Glu Phe Val Arg Gly Lys Val Ile Ala Thr Asp Leu85 90 95Asn Ser Asp Pro Lys Lys Val Tyr Thr Ile Asp Gly Arg Glu Phe Arg100 105 110Gly Lys Thr Ile Ile Val Ala Ser Gly Ala Met Glu Arg Ala Asn Lys115 120 125Phe Lys Gly Glu Glu Glu Phe Leu Gly Arg Gly Val Ser Tyr Cys Gly130 135 140Val Cys Asp Ala Ala Phe Phe Lys Asp Gln Pro Val Ala Val Ile Gly145 150155 160Asp Asp Asp Tyr Ala Ile Glu Glu Ala Glu Phe Ile Ala Arg Phe Ala165 170 175Asn Lys Val Phe Phe Val Val Pro Gly Ser Lys Ile Lys Ala Pro Pro180 185 190Glu Val Ile Glu His Phe Glu Lys Leu Pro Asn Val Glu Ile Leu Leu195 200 205Arg His Arg Pro Ile Glu Ile Val Gly Asp Gln Val Val Lys Gly Ile210 215 220Lys Leu Lys Asp Leu Glu Lys Lys Glu Glu Lys Leu Leu Glu Val Asn225 230 235 240Gly Val Phe Ile Phe Leu Gly Gly Thr Lys Pro Ser Val Asp Phe Leu245 250 255Met Gly Gln Val Glu Met Thr Glu Gly Asp Cys Ile Val Val Asn Glu260 265 270Glu Met Met Thr Ser Val Pro Gly Val Phe Ala Ala Gly Asp Val Leu275 280 285Cys Asn Glu Val Lys Gln Ala Val Val Ala Ala Ala Met Gly Cys Lys290 295 300Ala Ala Leu Ala Val Asp Lys Phe Leu Ser Gly Lys Lys Lys Ile Val305 310 315 320Pro Gln Trp210198211315212PRT213枯草芽孢桿菌400198Ser Glu Glu Lys Ile Tyr Asp Val Ile Ile Ile Gly Ala Gly Pro Ala1 5 10 15Gly Met Thr Ala Ala Val Tyr Thr Ser Arg Ala Asn Leu Ser Thr Leu20 25 30Met Ile Glu Arg Gly Ile Pro Gly Gly Gln Met Ala Asn Thr Glu Asp35 40 45Val Glu Asn Tyr Pro Gly Phe Glu Ser Ile Leu Gly Pro Glu Leu Ser50 55 60Asn Lys Met Phe Glu His Ala Lys Lys Phe Gly Ala Glu Tyr Ala Tyr65 70 75 80Gly Asp Ile Lys Glu Val Ile Asp Gly Lys Glu Tyr Lys Val Val Lys85 90 95Ala Gly Ser Lys Glu Tyr Lys Ala Arg Ala Val Ile Ile Ala Ala Gly100 105 110Ala Glu Tyr Lys Lys Ile Gly Val Pro Gly Glu Lys Glu Leu Gly Gly115 120 125Arg Gly Val Ser Tyr Cys Ala Val Cys Asp Gly Ala Phe Phe Lys Gly130 135 140Lys Glu Leu Val Val Val Gly Gly Gly Asp Ser Ala Val Glu Glu Gly145 150 155 160Val Tyr Leu Thr Arg Phe Ala Ser Lys Val Thr Ile Val His Arg Arg165 170 175Asp Lys Leu Arg Ala Gln Ser Ile Leu Gln Ala Arg Ala Phe Asp Asn180 185 190Glu Lys Val Asp Phe Leu Trp Asn Lys Thr Val Lys Glu Ile His Glu195 200 205Glu Asn Gly Lys Val Gly Asn Val Thr Leu Val Asp Thr Val Thr Gly210 215 220Glu Glu Ser Glu Phe Lys Thr Asp Gly Val Phe Ile Tyr Ile Gly Met225 230 235 240Leu Pro Leu Ser Lys Pro Phe Glu Asn Leu Gly Ile Thr Asn Glu Glu245 250 255Gly Tyr Ile Glu Thr Asn Asp Arg Met Glu Thr Lys Val Glu Gly Ile260 265 270Phe Ala Ala Gly Asp Ile Arg Glu Lys Ser Leu Arg Gln Ile Val Thr275 280 285Ala Thr Gly Asp Gly Ser Ile Ala Ala Gln Ser Val Gln His Tyr Val290 295 300Glu Glu Leu Gln Glu Thr Leu Lys Thr Leu Lys305 310 315210199211326212PRT213布氏疏螺旋體400199Met Leu Glu Phe Glu Thr Ile Asp Ile Asn Leu Thr Lys Lys Lys Asn1 5 10 15Leu Ser Gln Lys Glu Val Asp Phe Ile Glu Asp Val Ile Ile Val Gly20 25 30Ser Gly Pro Ala Gly Leu Thr Ala Gly Ile Tyr Ser Val Met Ser Asn35 40 45Tyr Lys Ala Ala Ile Leu Glu Gly Pro Glu Pro Gly Gly Gln Leu Thr50 55 60Thr Thr Thr Glu Val Tyr Asn Tyr Pro Gly Phe Lys Asn Gly Ile Ser65 70 75 80Gly Arg Asn Leu Met Leu Asn Met Arg Glu Gln Val Val Asn Leu Gly85 90 95Ala Lys Thr Phe Pro Glu Thr Val Phe Ser Ile Lys Arg Lys Gly Asn100 105 110Ile Phe Tyr Leu Tyr Thr Glu Asn Tyr Ile Tyr Lys Ser Lys Ala Val115 120 125Ile Ile Ala Val Gly Ser Lys Pro Lys Lys Leu Glu Thr Leu Lys Asn130 135 140Ser Gly Leu Phe Trp Asn Lys Gly Ile Ser Val Cys Ala Ile Cys Asp145 150 155 160Gly His Leu Phe Lys Gly Lys Arg Val Ala Val Ile Gly Gly Gly Asn165 170 175Thr Ala Leu Ser Glu Ser Ile Tyr Leu Ser Lys Leu Val Asp Lys Val180 185 190Tyr Leu Ile Val Arg Lys Asn Asn Leu Arg Ala Ile Ala Met Leu Arg195 200 205Asp Ser Val Ala Lys Leu Pro Asn Ile Glu Ile Leu Tyr Asn Ser Glu210 215 220Ala Ile Glu Val Asp Gly Lys Ser Ser Val Ser Ser Val Lys Ile Phe225 230 235 240Asn Lys Lys Asp Asn Val Val Tyr Glu Leu Glu Val Ser Ala Val Phe245 250 255Met Ala Val Gly Tyr Lys Pro Asn Thr Glu Phe Leu Lys Gly Phe Leu260 265 270Asp Leu Asp Glu Glu Gly Phe Ile Val Thr Lys Asp Val Val Lys Thr275 280 285Ser Val Asp Gly Val Phe Ser Cys Gly Asp Val Ser Asn Lys Leu Tyr290 295 300Ala Gln Ala Ile Thr Ala Ala Ala Glu Gly Phe Ile Ala Ser Val Glu305 310 315 320Leu Gly Asn Phe Leu Lys325210200211319212PRT213蚜蟲巴克納氏菌400200Met Asp Lys Val Lys His Ser Lys Ile Ile Ile Leu Gly Ser Gly Pro1 5 10 15Ala Gly Tyr Thr Ala Ala Ile Tyr Ala Ala Arg Ala Asn Leu Asp pro20 25 30phe Leu Ile Thr Gly Thr Asn Lys Gly Gly Gln Leu Met Asn Thr Asn
35 40 45Glu Ile Glu Asn Trp Pro Gly Asp Tyr Asn Lys Ile Ser Gly Ser Glu50 55 60Leu Met Asn Arg Met Tyr Lys His Ala Ile Glu Leu Lys Thr Lys Val65 70 75 80Ile Cys Asp Thr Val Ile Ser Val Asn Phe Lys Lys Asn Pro Phe Phe85 90 95Leu Ile Gly Glu Asn Asn Lys Tyr Thr Ala Asp Ser Val Ile Ile Ala100 105 110Thr Gly Ala Asn Pro Arg Tyr Leu Gly Leu Gln Ser Glu Ser Leu Phe115 120 125Lys Gly Lys Gly Val Ser Thr Cys Ala Val Cys Asp Gly Phe Phe Tyr130 135 140Lys Asn Lys Glu Val Ala Val Val Gly Gly Gly Asn Thr Ala Ile Glu145 150 155 160Glu Thr Leu Tyr Leu Ser Asn Phe Val Lys Lys Val His Leu Ile His165 170 175Arg Gly Ile Asn Phe Arg Ala Glu Lys Ile Leu Leu Asp Arg Leu Glu180 185 190Lys Lys Ile Lys Ser Gln Lys Ile Ile Ile Tyr Leu Asn Ser Ile Val195 200 205Lys Asn Ile Leu Gly Asn Ser Ser Gly Val Thr Ala Leu Leu Ile Glu210 215 220Gln Lys Asn Ser Lys Glu Lys Thr Glu Ser Lys Ile Gln Val Ser Gly225 230 235 240Leu Phe Val Ala Ile Gly Tyr Thr Pro Asn Thr Asn Ile Phe Val Asn245 250 255Lys Leu Lys Met Lys Asp Gly Tyr Ile Gln Val Thr Arg Gln Glu His260 265 270Gly Asn Tyr Thr Gln Thr Ser Ile Pro Gly Ile Phe Ala Ala Gly Asp275 280 285Val Ile Asp His Val Tyr Arg Gln Ala Ile Thr Ser Ser Ala Ser Gly290 295 300Cys Met Ala Ala Leu Asp Ser Glu Arg Tyr Ile Asn Ser Leu Val305310 315210201211319212PRT213蚜蟲巴克納氏菌400201Met Glu Leu Lys Asn His Lys Lys Ile Ile Ile Leu Gly Ser Gly Pro1 5 10 15Ala Gly Tyr Thr Ala Ala Ile Tyr Ser Ser Arg Ala Asn Leu Asn Pro20 25 30Leu Leu Ile Thr Gly Ile Asn Lys Gly Gly Gln Leu Met Asn Thr Asn35 40 45Glu Ile Glu Asn Trp Pro Gly Asp Phe Lys Lys Ile Thr Gly Pro Glu50 55 60Leu Met Asn Arg Met His Glu His Ser Leu Lys Phe Lys Thr Glu Ile65 70 75 80Val Tyr Asp Asn Ile Ile Ser Val Glu Phe Lys Lys Lys Pro Phe Phe85 90 95Leu Leu Gly Glu Tyr Asn Lys Tyr Thr Cys Asp Ala Val Ile Ile Ala100 105 110Thr Gly Ala Asn Pro Arg Tyr Leu Gly Leu Ser Ser Glu Asn Lys Phe115 120 125Lys Gly Lys Gly Ile Ser Thr Cys Ala Val Cys Asp Gly Phe Phe Tyr130 135 140Lys Asn Lys Glu Ile Ala Val Val Gly Gly Gly Asn Thr Ala Ile Glu145 150 155 160Glu Thr Leu Tyr Leu Ser Asn Phe Val Lys Lys Ile Tyr Leu Ile His165170 175Arg Arg Asn Asn Phe Lys Ala Glu Lys Ile Leu Ile Asp Arg Leu Leu180 185 190Lys Ile Val Lys Thr Lys Lys Val Ile Leu His Leu Asn Ser Thr Ile195 200 205Glu Asp Ile Leu Gly Asn Asn Lys Gly Val Thr His Leu Leu Ile Lys210 215 220Asn Lys Asn Leu Lys Glu Lys Lys Lys Leu Lys Ile Ala Val Ser Gly225 230 235 240Leu Phe Val Ala Ile Gly Tyr Ile Pro Asn Thr Asp Ile Phe Thr Asp245 250 255Gln Leu Lys Met Lys Asp Gly Tyr Ile Lys Ile Lys Lys Gly Thr His260 265 270Gly Asn Tyr Thr Gln Thr Asn Ile Pro Gly Val Phe Ala Ala Gly Asp275 280 285Val Ile Asp His Val Tyr Arg Gln Ala Ile Thr Ser Ser Ala Ser Gly290 295 300Cys Met Ala Ala Leu Asp Ser Glu Arg Tyr Leu Asn Ser Leu Ser305310 315210202211312212PRT213Chlamydia muridarum400202Met Thr His Val Lys Leu Ala Ile Ile Gly Ser Gly Pro Ala Gly Tyr1 5 10 15Thr Ala Ala Ile Tyr Ala Ser Arg Ala Leu Leu Thr Pro Ile Leu Phe20 25 30Glu Gly Phe Phe Ser Gly Ile Ala Gly Gly Gln Leu Met Thr Thr Thr35 40 45Glu Val Glu Asn Phe Pro Gly Phe Pro Gln Gly Val Leu Gly His Gln50 55 60Leu Met Glu Asn Met Lys Met Gln Ala Gln Arg Phe Gly Thr Gln Val65 70 75 80Ile Ala Lys Asp Ile Thr Ser Val Asp Phe Ser Val Arg Pro Phe Val85 90 95Leu Lys Ser Gly Glu Asp Thr Phe Thr Cys Asp Ala Cys Ile Ile Ala100 105 110Thr Gly Ala Ser Ala Lys Arg Leu Ser Ile Pro Gly Ala Gly Asp Asn115 120 125Glu Phe Trp Gln Lys Gly Val Thr Ala Cys Ala Val Cys Asp Gly Ala130 135 140Ser Pro Ile Phe Arg Asp Arg Asp Leu Phe Val Ile Gly Gly Gly Asp145 150 155 160Ser Ala Leu Glu Glu Ala Met Phe Leu Thr Arg Tyr Gly Lys Arg Val165 170 175Phe Val Val His Arg Arg Asp Thr Leu Arg Ala Ser Lys Ala Met Val180 185 190Asn Lys Ala Gln Ala Asn Glu Lys Ile Val Phe Leu Trp Asn Ser Glu195 200 205Val Val Lys Ile Leu Gly Asp Ser Leu Val Arg Ser Ile Asp Ile Phe210 215 220Asn Asn Val Glu Lys Thr Thr Val Thr Met Glu Ala Ala Gly Val Phe225 230 235 240Phe Ala Ile Gly His Gln Pro Asn Thr Ala Phe Leu Gly Gly Gln Leu245 250 255Ser Leu Asp Glu Asn Gly Tyr Ile Ile Thr Glu Lys Gly Ser Ser Arg260 265 270Thr Ser Val Pro Gly Val Phe Ala Ala Gly Asp Val Gln Asp Lys Tyr275 280 285Tyr Arg Gln Ala Ile Thr Ser Ala Gly Ser Gly Cys Met Ala Ala Leu290 295 300Asp Ala Glu Arg Phe Leu Glu Lys305 310210203211311212PRT213肺炎衣原體400203Met Ile His Ser Arg Leu Ile Ile Ile Gly Ser Gly Pro Ser Gly Tyr1 5 10 15Thr Ala Ala Ile Tyr Ala Ser Arg Ala Leu Leu His Pro Leu Leu Phe20 25 30Glu Gly Phe Phe Ser Gly Ile Ser Gly Gly Gln Leu Met Thr Thr Thr35 40 45Glu Val Glu Asn Phe Pro Gly Phe Pro Glu Gly Ile Leu Gly Pro Lys50 55 60Leu Met Asn Asn Met Lys Glu Gln Ala Val Arg Phe Gly Thr Lys Thr65 70 75 80Leu Ala Gln Asp Ile Ile Ser Val Asp Phe Ser Val Arg Pro Phe Ile85 90 95Leu Lys Ser Lys Glu Glu Thr Tyr Ser Cys Asp Ala Cys Ile Ile Ala100 105 110Thr Gly Ala Ser Ala Lys Arg Leu Glu Ile Pro Gly Ala Gly Asn Asp115 120 125Glu Phe Trp Gln Lys Gly Val Thr Ala Cys Ala Val Cys Asp Gly Ala130 135 140Ser Pro Ile Phe Lys Asn Lys Asp Leu Tyr Val Ile Gly Gly Gly Asp145 150 155 160Ser Ala Leu Glu Glu Ala Leu Tyr Leu Thr Arg Tyr Gly Ser His Val165 170 175Tyr Val Val His Arg Arg Asp Lys Leu Arg Ala Ser Lys Ala Met Glu180 185 190Ala Arg Ala Gln Asn Asn Glu Lys Ile Thr Phe Leu Trp Asn Ser Glu195 200 205Ile Val Lys Ile Ser Gly Asp Ser Ile Val Arg Ser Val Asp Ile Lys210 215 220Asn Val Gln Thr Gln Glu Ile Thr Thr Arg Glu Ala Ala Gly Val Phe225 230 235 240Phe Ala Ile Gly His Lys Pro Asn Thr Asp Phe Leu Gly Gly Gln Leu245 250 255Thr Leu Asp Glu Ser Gly Tyr Ile Val Thr Glu Lys Gly Thr Ser Lys260 265 270Thr Ser Val Pro Gly Val Phe Ala Ala Gly Asp Val Gln Asp Lys Tyr275 280 285Tyr Arg Gln Ala Val Thr Ser Ala Gly Ser Gly Cys Ile Ala Ala Leu290 295 300Asp Ala Glu Arg Phe Leu Gly305 310210204211312212PRT213砂眼衣原體400204Met Thr His Ala Lys Leu Val Ile Ile Gly Ser Gly Pro Ala Gly Tyr1 5 10 15Thr Ala Ala Ile Tyr Ala Ser Arg Ala Leu Leu Thr Pro Val Leu Phe20 25 30Glu Gly Phe Phe Ser Gly Ile Ala Gly Gly Gln Leu Met Thr Thr Thr35 40 45Glu Val Glu Asn Phe Pro Gly Phe Pro Glu Gly Val Leu Gly His Gln50 55 60Leu Met Asp Leu Met Lys Thr Gln Ala Gln Arg Phe Gly Thr Gln Val65 70 75 80Leu Ser Lys Asp Ile Thr Ala Val Asp Phe Ser Val Arg Pro Phe Val85 90 95Leu Lys Ser Gly Lys Glu Thr Phe Thr Cys Asp Ala Cys Ile Ile Ala100 105 110Thr Gly Ala Ser Ala Lys Arg Leu Ser Ile Pro Gly Ala Gly Asp Asn115 120 125Glu Phe Trp Gln Lys Gly Val Thr Ala Cys Ala Val Cys Asp Gly Ala130 135 140Ser Pro Ile Phe Arg Asp Lys Asp Leu Phe Val Val Gly Gly Gly Asp145 150 155 160Ser Ala Leu Glu Glu Ala Met Phe Leu Thr Arg Tyr Gly Lys Arg Val165 170 175Phe Val Val His Arg Arg Asp Thr Leu Arg Ala Ser Lys Val Met Val180 185 190Asn Lys Ala Gln Ala Asn Glu Lys Ile Phe Phe Leu Trp Asn Ser Glu195 200 205Ile Val Lys Ile Ser Gly Asp Thr Leu Val Arg Ser Ile Asp Ile Tyr210 215 220Asn Asn Val Asp Glu Thr Thr Thr Thr Met Glu Ala Ala Gly Val Phe225 230 235 240Phe Ala Ile Gly His Gln Pro Asn Thr Ala Phe Leu Gly Gly Gln Val245 250 255Ala Leu Asp Glu Asn Gly Tyr Ile Ile Thr Glu Lys Gly Ser Ser Arg260 265 270Thr Ser Val Pro Gly Val Phe Ala Ala Gly Asp Val Gln Asp Lys Tyr275 280 285Tyr Arg Gln Ala Ile Thr Ser Ala Gly Ser Gly Cys Met Ala Ala Leu290 295 300Asp Ala Glu Arg Phe Leu Glu Asn305 310210205211315212PRT213海濱梭菌400205Met Glu Asn Val Tyr Asp Ile Ala Ile Ile Gly Ser Gly Pro Ala Gly1 5 10 15Leu Ala Ala Ala Leu Tyr Gly Ala Arg Ala Lys Met Lys Thr Leu Leu20 25 30Leu Glu Gly Met Lys Val Gly Gly Gln Ile Val Ile Thr His Glu Val35 40 45Ala Asn Tyr Pro Gly Ser Val Pro Glu Ala Thr Gly Pro Ser Leu Ile50 55 60Gly Arg Met Glu Glu Gln Val Glu Glu Phe Gly Ala Glu Arg Val Met65 70 75 80Asp Asn Ile Val Asp Val Asp Phe Thr Asp Lys Ile Lys Val Leu Lys85 90 95Gly Ala Lys Gly Glu Tyr Lys Ala Lys Ala Val Ile Val Ala Thr Gly100 105 110Ala Ser Pro Lys Leu Ala Gly Cys Pro Gly Glu Lys Glu Leu Thr Gly115 120 125Lys Gly Val Ser Tyr Cys Ala Thr Cys Asp Ala Asp Phe Phe Glu Asp130 135 140Met Glu Val Phe Val Ile Gly Gly Gly Asp Thr Ala Val Glu Glu Ala145 150 155 160Met Phe Leu Thr Lys Phe Ala Arg Lys Val Thr Ile Val His Arg Arg165 170 175Ala Glu Leu Arg Ala Ala Lys Ser Ile Gln Glu Lys Ala Phe Lys Asn180 185 190Glu Lys Leu Asn Phe Met Trp Asn Thr Val Ile Glu Glu Ile Lys Gly195 200 205Asp Gly Ile Val Glu Ser Ala Val Phe Lys Asn Arg Glu Thr Gly Glu210 215 220Val Thr Glu Phe Val Ala Pro Glu Glu Asp Gly Thr Phe Gly Ile Phe225 230 235 240Val Phe Ile Gly Tyr Asp Pro Lys Ser Ala Leu Val Glu Gly Lys Leu245 250 255Glu Leu Asp Glu Thr Gly Tyr Ile Pro Thr Asp Asp Asn Met Lys Thr
260 265270Asn Val Glu Gly Val Phe Ala Ala Gly Asp Ile Arg Val Lys Ser Leu275 280 285Arg Gln Val Val Thr Ala Thr Ala Asp Gly Ala Ile Ala Ala Val Gln290 295 300Ala Glu Lys Tyr Ile Glu Glu Leu Phe Ala Glu305 310 315210206211321212PRT213伯氏考克斯氏體(Coxiella burnetii)400206Met Asn Lys Pro Gln His His Ser Leu Ile Ile Leu Gly Ser Gly Pro1 5 10 15Ala Gly Tyr Thr Asp Ala Ile Tyr Val Ala Arg Ala Asn Leu Lys Pro20 25 30Ile Met Ile Thr Gly Met Glu Gln Gly Gly Gln Leu Met Thr Thr Thr35 40 45Asp Val Ala Asn Trp Pro Gly Glu Ala Pro Gly Leu Gln Gly Pro Lys50 55 60Leu Leu Glu Arg Met Gln Lys His Ala Gly Gly Ala Leu Asn Thr Gln65 70 75 80Phe Ile Phe Asp His Ile Asn Lys Pro Asp Leu Asn Pro Arg Pro Phe85 90 95Leu Leu Gln Gly Asp Asn Ala Thr Tyr Ser Cys Asp Ala Leu Ile Ile100 105 110Ala Thr Gly Ala Ser Ala Arg Tyr Leu Gly Leu Pro Ser Glu Lys Pro115 120 125Tyr Met Gly Lys Gly Val Ser Ala Cys Ala Thr Cys Asp Gly Phe Phe130 135 140Tyr Arg Ala Lys Lys Val Ala Val Val Gly Gly Gly Asn Thr Ser Val145 150 155 160Glu Glu Ala Leu Tyr Leu Ser His Ile Ala Ser His Val Thr Leu Ile165 170 175His Arg Arg Asp Lys Leu Arg Ala Glu Lys Met Leu Ser Ala Gln Leu180 185 190Ile Lys Lys Val Glu Glu Gly Lys Val Ala Ile Val Trp Ser His Val195 200 205Ile Glu Glu Val Leu Gly Asp Asp Gln Gly Val Thr Gly Val His Leu210 215 220Lys His Val Lys Glu Glu Lys Thr Gln Asp Leu Thr Ile Asp Gly Leu225 230 235 240Phe Ile Ala Ile Gly His Asp Pro Asn Thr Lys Ile Phe Lys Glu Gln245 250 255Leu Glu Met Asp Glu Ala Gly Tyr Leu Arg Ala Lys Ser Gly Leu Gln260 265 270Gly Asn Ala Thr Ala Thr Asn Ile Pro Gly Val Phe Pro Ala Val Val275 280 285Val Arg Gly Gln Leu Tyr Arg Gln Thr Ile Ala Ala Ala Gly Met Gly290 295 300Cys Met Pro Ala Leu Asp Ala Glu Arg Tyr Leu Asp Ser Leu Asn Gln305 310 315 320Ala210207211320212PRT213大腸埃希氏桿菌400207Gly Thr Thr Lys His Ser Lys Leu Leu Ile Leu Gly Ser Gly Pro Ala1 5 10 15Gly Tyr Thr Ala Ala Val Tyr Ala Ala Arg Ala Asn Leu Gln Pro Val20 25 30Leu Ile Thr Gly Met Glu Lys Gly Gly Gln Leu Thr Thr Thr Thr Glu35 40 45Val Glu Asn Trp Pro Gly Asp Pro Asn Asp Leu Thr Gly Pro Leu Leu50 55 60Met Glu Arg Met His Glu His Ala Thr Lys Phe Glu Thr Glu Ile Ile65 70 75 80Phe Asp His Ile Asn Lys Val Asp Leu Gln Asn Arg Pro Phe Arg Leu85 90 95Asn Gly Asp Asn Gly Glu Tyr Thr Cys Asp Ala Leu Ile Ile Ala Thr100 105 110Gly Ala Ser Ala Arg Tyr Leu Gly Leu Pro Ser Glu Glu Ala Phe Lys115 120 125Gly Arg Gly Val Ser Ala Cys Ala Thr Cys Asp Gly Phe Phe Tyr Arg130 135 140Asn Gln Lys Val Ala Val Ile Gly Gly Gly Asn Thr Ala Val Glu Glu145 150 155 160Ala Leu Tyr Leu Ser Asn Ile Ala Ser Glu Val His Leu Ile His Arg165 170 175Arg Asp Gly Phe Arg Ala Glu Lys Ile Leu Ile Lys Arg Leu Met Asp180 185 190Lys Val Glu Asn Gly Asn Ile Ile Leu His Thr Asn Arg Thr Leu Glu195 200 205Glu Val Thr Gly Asp Gln Met Gly Val Thr Gly Val Arg Leu Arg Asp210 215 220Thr Gln Asn Ser Asp Asn Ile Glu Ser Leu Asp Val Ala Gly Leu Phe225 230 235 240Val Ala Ile Gly His Ser Pro Asn Thr Ala Ile Phe Glu Gly Gln Leu245 250 255Glu Leu Glu Asn Gly Tyr Ile Lys Val Gln Ser Gly Ile His Gly Asn260 265 270Ala Thr Gln Thr Ser Ile Pro Gly Val Phe Ala Ala Gly Asp Val Met275 280 285Asp His Ile Tyr Arg Gln Ala Ile Thr Ser Ala Gly Thr Gly Cys Met290 295 300Ala Ala Leu Asp Ala Glu Arg Tyr Leu Asp Gly Leu Ala Asp Ala Lys305 310 315 320210208211315212PRT213嗜胺基酸真桿菌400208Met Glu Asn Val Tyr Asp Leu Ala Ile Ile Gly Ser Gly Pro Ala Gly1 5 10 15Leu Ala Ala Ala Leu Tyr Gly Ala Arg Ala Lys Met Lys Thr Ile Met20 25 30Ile Glu Gly Gln Lys Val Gly Gly Gln Ile Val Ile Thr His Glu Val35 40 45Ala Asn Tyr Pro Gly Ser Val Arg Glu Ala Thr Gly Pro Ser Leu Ile50 55 60Glu Arg Met Glu Glu Gln Ala Asn Glu Phe Gly Ala Glu Lys Val Met65 70 75 80Asp Lys Ile Val Asp Val Asp Leu Asp Gly Lys Ile Lys Val Ile Lys85 90 95Gly Glu Lys Ala Glu Tyr Lys Ala Lys Ser Val Ile Leu Ala Thr Gly100 105 110Ala Ala Pro Arg Leu Ala Gly Cys Pro Gly Glu Gln Glu Leu Thr Gly115 120 125Lys Gly Val Ser Tyr Cys Ala Thr Cys Asp Ala Asp Phe Phe Glu Asp130 135 140Met Glu Val Phe Val Val Gly Gly Gly Asp Thr Ala Val Glu Glu Ala145 150 155 160Met Tyr Leu Ala Lys Phe Ala Arg Lys Val Thr Ile Val His Arg Arg
165 170 175Asp Glu Leu Arg Ala Ala Lys Ser Ile Gln Glu Lys Ala Phe Lys Asn180 185 190Pro Lys Leu Asp Phe Met Trp Asn Ser Ala Ile Glu Glu Ile Lys Gly195 200 205Asp Gly Ile Val Glu Ser Ala Val Phe Lys Asn Leu Val Thr Gly Glu210 215 220Thr Thr Glu Tyr Phe Ala Asn Glu Glu Asp Gly Thr Phe Gly Ile Phe225 230 235 240Val Phe Ile Gly Tyr Ile Pro Lys Ser Asp Val Phe Lys Gly Lys Ile245 250 255Thr Leu Asp Asp Ala Gly Tyr Ile Ile Thr Asp Asp Asn Met Lys Thr260 265 270Asn Val Glu Gly Val Phe Ala Ala Gly Asp Ile Arg Val Lys Ser Leu275 280 285Arg Gln Val Val Thr Ala Cys Ala Asp Gly Ala Ile Ala Ala Thr Gln290 295 300Ala Glu Lys Tyr Val Glu Ala Asn Phe Glu Glu305 310 315210209211318212PRT213流感嗜血桿菌400209Met Ser Asp Ile Lys His Ala Lys Leu Leu Ile Leu Gly Ser Gly Pro1 5 10 15Ala Gly Tyr Thr Ala Ala Ile Tyr Ala Ala Arg Ala Asn Leu Lys Pro20 25 30Val Leu Val Thr Gly Leu Gln Gln Gly Gly Gln Leu Thr Thr Thr Asp35 40 45Glu Ile Glu Asn Trp Pro Gly Asp Phe Glu Met Thr Thr Gly Ser Gly50 55 60Leu Met Gln Arg Met Leu Gln His Ala Glu Lys Phe Glu Thr Glu Ile65 70 75 80Val Phe Asp His Ile Asn Arg Val Asp Leu Ser Ser Arg Pro Phe Lys85 90 95Leu Phe Gly Asp Val Gln Asn Phe Thr Cys Asp Ala Leu Ile Ile Ala100 105 110Thr Gly Ala Ser Ala Arg Tyr Ile Gly Leu Pro Ser Glu Glu Asn Tyr115 120 125Lys Gly Arg Gly Val Ser Ala Cys Ala Thr Cys Asp Gly Phe Phe Tyr130 135 140Arg Asn Lys Pro Val Gly Val Ile Gly Gly Gly Asn Thr Ala Val Glu145 150 155 160Glu Ala Leu Tyr Leu Ala Asn Ile Ala Ser Thr Val His Leu Ile His165 170 175Arg Arg Asp Ser Phe Arg Ala Glu Lys Ile Leu Ile Asp Arg Leu Tyr180 185 190Lys Lys Val Glu Glu Gly Lys Ile Val Leu His Thr Asp Arg Thr Leu195 200 205Asp Glu Val Leu Gly Asp Asn Met Gly Val Thr Gly Leu Arg Leu Ala210 215 220Asn Thr Lys Thr Gly Glu Lys Glu Glu Leu Lys Leu Asp Gly Leu Phe225 230 235 240Val Ala Ile Gly His Ser Pro Asn Thr Glu Ile Phe Gln Gly Gln Leu245 250 255Glu Leu Asn Asn Gly Tyr Ile Val Val Lys Ser Gly Leu Asp Gly Asn260 265 270Ala Thr Ala Thr Ser Val Glu Gly Val Phe Ala Ala Gly Asp Val Met275 280 285Asp His Asn Tyr Arg Gln Ala Ile Thr Ser Ala Gly Thr Gly Cys Met290 295 300Ala Ala Leu Asp Ala Glu Arg Tyr Leu Asp Ala Gln Glu Ala305 310 315210210211311212PRT213幽門螺桿菌400210Met Ile Asp Cys Ala Ile Ile Gly Gly Gly Pro Ala Gly Leu Ser Ala1 5 10 15Gly Leu Tyr Ala Thr Arg Gly Gly Val Lys Asn Ala Val Leu Phe Glu20 25 30Lys Gly Met Pro Gly Gly Gln Ile Thr Gly Ser Ser Glu Ile Glu Asn35 40 45Tyr Pro Gly Val Lys Glu Val Val Ser Gly Leu Asp Phe Met Gln Pro50 55 60Trp Gln Glu Gln Cys Phe Arg Phe Gly Leu Lys His Glu Met Thr Ala65 70 75 80Ile Gln Arg Val Ser Lys Lys Gly Ser His Phe Val Ile Leu Ala Glu85 90 95Asp Gly Lys Thr Phe Glu Ala Lys Ser Val Ile Ile Ala Thr Gly Gly100 105 110Ser Pro Lys Arg Thr Gly Ile Lys Gly Glu Ser Glu Tyr Trp Gly Lys115 120 125Gly Val Ser Thr Cys Ala Thr Cys Asp Gly Phe Phe Tyr Lys Asn Lys130 135 140Glu Val Ala Val Leu Gly Gly Gly Asp Thr Ala Val Glu Glu Ala Ile145 150 155 160Tyr Leu Ala Asn Ile Cys Lys Lys Val Tyr Leu Ile His Arg Arg Asp165 170 175Gly Phe Arg Cys Ala Pro Ile Thr Leu Glu His Ala Lys Asn Asn Ser180 185 190Lys Ile Glu Phe Leu Thr Pro Tyr Val Val Glu Glu Ile Lys Gly Asp195 200 205Ala Ser Gly Val Ser Ser Leu Ser Ile Lys Asn Thr Ala Thr Asn Glu210 215 220Lys Arg Glu Leu Val Val Pro Gly Leu Phe Ile Phe Val Gly Tyr Asp225 230 235 240Val Asn Asn Ala Val Leu Lys Gln Glu Asp Asn Ser Met Leu Cys Glu245 250 255Cys Asp Glu Tyr Gly Ser Ile Val Val Asp Phe Ser Met Lys Thr Asn260 265 270Val Gln Gly Leu Phe Ala Ala Gly Asp Ile Arg Ile Phe Ala Pro Lys275 280 285Gln Val Val Cys Ala Ala Ser Asp Gly Ala Thr Ala Ala Leu Ser Val290 295 300Ile Ser Tyr Leu Glu His His305 310210211211311212PRT213幽門螺桿菌400211Met Ile Asp Cys Ala Ile Ile Gly Gly Gly Pro Ala Gly Leu Ser Ala1 5 10 15Gly Leu Tyr Ala Thr Arg Gly Gly Val Lys Asn Ala Val Leu Phe Glu20 25 30Lys Gly Met Pro Gly Gly Gln Ile Thr Gly Ser Ser Glu Ile Glu Asn35 40 45Tyr Pro Gly Val Lys Glu Val Val Ser Gly Leu Asp Phe Met Gln Pro50 55 60Trp Gln Glu Gln Cys Phe Arg Phe Gly Leu Lys His Glu Met Thr Ala65 70 75 80Val Gln Arg Val Ser Lys Lys Asp Ser His Phe Val Ile Leu Ala Glu85 90 95Asp Gly Lys Thr Phe Glu Ala Lys Ser Val Ile Ile Ala Thr Gly Gly100 105 110Ser Pro Lys Arg Thr Gly Ile Lys Gly Glu Ser Glu Tyr Trp Gly Lys115 120 125Gly Val Ser Thr Cys Ala Thr Cys Asp Gly Phe Phe Tyr Lys Asn Lys130 135 140Glu Val Ala Val Leu Gly Gly Gly Asp Thr Ala Val Glu Glu Ala Ile145 150 155 160Tyr Leu Ala Asn Ile Cys Lys Lys Val Tyr Leu Ile His Arg Arg Asp165 170 175Gly Phe Arg Cys Ala Pro Ile Thr Leu Glu His Ala Lys Asn Asn Asp180 185 190Lys Ile Glu Phe Leu Thr Pro Tyr Val Val Glu Glu Ile Lys Gly Asp195 200 205Ala Ser Gly Val Ser Ser Leu Ser Ile Lys Asn Thr Ala Thr Asn Glu210 215 220Lys Arg Glu Leu Val Val Pro Gly Phe Phe Ile Phe Val Gly Tyr Asp225 230 235 240Val Asn Asn Ala Val Leu Lys Gln Glu Asp Asn Ser Met Leu Cys Lys245 250 255Cys Asp Glu Tyr Gly Ser Ile Val Val Asp Phe Ser Met Lys Thr Asn260 265 270Val Gln Gly Leu Phe Ala Ala Gly Asp Ile Arg Ile Phe Ala Pro Lys275 280 285Gln Val Val Cys Ala Ala Ser Asp Gly Ala Thr Ala Ala Leu Ser Val290 295 300Ile Ser Tyr Leu Glu His His305 310210212211319212PRT213單核細胞增生利斯特氏菌400212Met Ala Ser Glu Glu Lys Ile Tyr Asp Val Ile Ile Ile Gly Ala Gly1 5 10 15Pro Ala Gly Met Thr Ala Ala Leu Tyr Thr Ser Arg Ala Asp Leu Asp20 25 30Thr Leu Met Ile Glu Arg Gly Val Pro Gly Gly Gln Met Val Asn Thr35 40 45Ala Glu Val Glu Asn Tyr Pro Gly Phe Asp Ser Ile Leu Gly Pro Asp50 55 60Leu Ser Asp Lys Met Leu Ser Gly Ala Lys Gln Phe Gly Ala Glu Tyr65 70 75 80Ala Tyr Gly Asp Ile Lys Glu Val Val Asp Gly Lys Glu Phe Lys Thr85 90 95Val Thr Ala Gly Ser Lys Thr Tyr Lys Ala Arg Ala Ile Ile Ile Ala100 105 110Thr Gly Ala Glu His Arg Lys Leu Gly Ala Ala Gly Glu Glu Glu Leu115 120 125Ser Gly Arg Gly Val Ser Tyr Cys Ala Val Cys Asp Gly Ala Phe Phe130 135 140Lys Asn Arg Glu Leu Ile Val Val Gly Gly Gly Asp Ser Ala Val Glu145 150 155 160Glu Gly Thr Tyr Leu Thr Arg Tyr Ala Asp Lys Val Thr Ile Val His165 170 175Arg Arg Asp Lys Leu Arg Ala Gln Gln Ile Leu Gln Asp Arg Ala Phe180 185 190Lys Asp Glu Lys Val Asp Phe Ile Trp Asn Ser Thr Val Glu Glu Ile195 200 205Val Gly Asp Gly Lys Lys Val Thr Gly Ala Lys Leu Val Ser Thr Val210 215 220Asp Gly Ser Glu Ser Ile Met Pro Val Asp Gly Val Phe Ile Tyr Val225 230 235 240Gly Leu Val Pro Leu Thr Lys Ala Phe Leu Asn Leu Gly Ile Thr Asp
245 250 255Asp Glu Gly Tyr Ile Val Thr Asp Glu Glu Met Arg Thr Asn Leu Pro260 265 270Gly Ile Phe Ala Ala Gly Asp Val Arg Ala Lys Ser Leu Arg Gln Ile275 280 285Val Thr Ala Thr Gly Asp Gly Gly Leu Ala Gly Gln Asn Ala Gln Lys290 295 300Tyr Val Glu Glu Leu Lys Glu Ser Leu Glu Ala Glu Ala Ala Lys305 310 315210213211315212PRT213生殖道枝原體400213Met Leu Lys Val Asn Ala Asp Phe Leu Thr Lys Asp Gln Val Ile Tyr1 5 10 15Asp Leu Val Ile Val Gly Ala Gly Pro Ala Gly Ile Ala Ser Ala Ile20 25 30Tyr Gly Lys Arg Ala Asn Leu Asn Leu Ala Ile Ile Glu Gly Asn Thr35 40 45Pro Gly Gly Lys Ile Val Lys Thr Asn Ile Val Glu Asn Tyr Pro Gly50 55 60Phe Lys Thr Ile Thr Gly Pro Glu Leu Gly Leu Glu Met Tyr Asn His65 70 75 80Leu Leu Ala Phe Glu Pro Val Val Phe Tyr Asn Asn Leu Ile Lys Ile85 90 95Asp His Leu Asn Asp Thr Phe Ile Leu Tyr Leu Asp Asn Lys Thr Thr100 105 110Val Phe Ser Lys Thr Val Ile Tyr Ala Thr Gly Met Glu Glu Arg Lys115 120 125Leu Gly Ile Glu Lys Glu Asp Tyr Phe Tyr Gly Lys Gly Ile Ser Tyr130 135 140Cys Ala Ile Cys Asp Ala Ala Leu Tyr Lys Gly Lys Thr Val Gly Val145 150 155 160Val Gly Gly Gly Asn Ser Ala Ile Gln Glu Ala Ile Tyr Leu Ser Ser165 170 175Ile Ala Lys Thr Val His Leu Ile His Arg Arg Glu Val Phe Arg Ser180 185 190Asp Ala Leu Leu Val Glu Lys Leu Lys Lys Ile Ser Asn Val Val Phe195 200 205His Leu Asn Ala Thr Val Lys Gln Leu Ile Gly Gln Glu Lys Leu Gln210 215 220Thr Val Lys Leu Ala Ser Thr Val Asp Lys Ser Glu Ser Glu Ile Ala225 230 235 240Ile Asp Cys Leu Phe Pro Tyr Ile Gly Phe Glu Ser Asn Asn Lys Pro245 250 255Val Leu Asp Leu Lys Leu Asn Leu Asp Gln Asn Gly Phe Ile Leu Gly260 265 270Asp Glu Asn Met Gln Thr Asn Ile Lys Gly Phe Tyr Val Ala Gly Asp275 280 285Cys Arg Ser Lys Ser Phe Arg Gln Ile Ala Thr Ala Ile Ser Asp Gly290 295 300Val Thr Ala Val Leu Lys Val Arg Asp Asp Ile305 310 315210214211458212PRT213麻瘋分枝桿菌400214Met Asn Thr Thr Pro Ser Ala His Glu Thr Ile His Glu Val Ile Val15 10 15Ile Gly Ser Gly Pro Ala Gly Tyr Thr Ala Ala Leu Tyr Ala Ala Arg20 25 30Ala Gln Leu Thr Pro Leu Val Phe Glu Gly Thr Ser Phe Gly Gly Ala35 40 45Leu Met Thr Thr Thr Glu Val Glu Asn Tyr Pro Gly Phe Arg Asn Gly50 55 60Ile Thr Gly Pro Glu Leu Met Asp Asp Met Arg Glu Gln Ala Leu Arg65 70 75 80Phe Gly Ala Glu Leu Arg Thr Glu Asp Val Glu Ser Val Ser Leu Arg85 90 95Gly Pro Ile Lys Ser Val Val Thr Ala Glu Gly Gln Thr Tyr Gln Ala100 105 110Arg Ala Val Ile Leu Ala Met Gly Thr Ser Val Arg Tyr Leu Gln Ile115 120 125Pro Gly Glu Gln Glu Leu Leu Gly Arg Gly Val Ser Ala Cys Ala Thr130 135 140Cys Asp Gly Ser Phe Phe Arg Gly Gln Asp Ile Ala Val Ile Gly Gly145 150 155 160Gly Asp Ser Ala Met Glu Glu Ala Leu Phe Leu Thr Arg Phe Ala Arg165 170 175Ser Val Thr Leu Val His Arg Arg Asp Glu Phe Arg Ala Ser Lys Ile180 185 190Met Leu Gly Arg Ala Arg Asn Asn Asp Lys Ile Lys Phe Ile Thr Asn195 200 205His Thr Val Val Ala Val Asn Gly Tyr Thr Thr Val Thr Gly Leu Arg210 215 220Leu Arg Asn Thr Thr Thr Gly Glu Glu Thr Thr Leu Val Val Thr Gly225 230 235 240Val Phe Val Ala Ile Gly His Glu Pro Arg Ser Ser Leu Val Ser Asp245 250 255Val Val Asp Ile Asp Pro Asp Gly Tyr Val Leu Val Lys Gly Arg Thr260 265 270Thr Ser Thr Ser Met Asp Gly Val Phe Ala Ala Gly Asp Leu Val Asp275 280 285Arg Thr Tyr Arg Gln Ala Ile Thr Ala Ala Gly Ser Gly Cys Ala Ala290 295 300Ala Ile Asp Ala Glu Arg Trp Leu Ala Glu His Ala Gly Ser Lys Ala305 310 315 320Asn Glu Thr Thr Glu Glu Thr Gly Asp Val Asp Ser Thr Asp Thr Thr325 330 335Asp Trp Ser Thr Ala Met Thr Asp Ala Lys Asn Ala Gly Val Thr Ile340 345 350Glu Val Thr Asp Ala Ser Phe Phe Ala Asp Val Leu Ser Ser Asn Lys355 360 365Pro Val Leu Val Asp Phe Trp Ala Thr Trp Cys Gly Pro Cys Lys Met370 375 380Val Ala Pro Val Leu Glu Glu Ile Ala Ser Glu Gln Arg Asn Gln Leu385 390 395 400Thr Val Ala Lys Leu Asp Val Asp Thr Asn Pro Glu Met Ala Arg Glu405 410 415Phe Gln Val Val Ser Ile Pro Thr Met Ile Leu Phe Gln Gly Gly Gln420 425 430Pro Val Lys Arg Ile Val Gly Ala Lys Gly Lys Ala Ala Leu Leu Arg435 440 445Asp Leu Ser Asp Val Val Pro Asn Leu Asn450 455210215211315212PRT213肺炎枝原體400215Met Leu Lys Val Lys Ser Asp Phe Leu Thr Lys Asp Gln Val Ile Tyr1 5 10 15Asp Val Ala Ile Val Gly Ala Gly Pro Ala Gly Ile Ala Ala Gly Ile
20 25 30Tyr Gly Lys Arg Ala Asn Leu Asn Leu Ala Ile Ile Glu Gly Ser Thr35 40 45Pro Gly Gly Lys Val Val Lys Thr Asn Ile Val Glu Asn Tyr Pro Gly50 55 60Tyr Lys Ser Ile Thr Gly Pro Asp Leu Gly Leu Glu Met Tyr Asn His65 70 75 80Leu Ile Asp Leu Glu Pro Thr Phe Phe Tyr Ala Asn Leu Ile Lys Leu85 90 95Asp Lys Ala Ala Asp Thr Phe Ile Leu Tyr Leu Asp Asp Lys Thr Val100 105 110Val Phe Ala Lys Thr Val Ile Tyr Ala Thr Gly Met Leu Glu Arg Lys115 120 125Leu Gly Val Ala Lys Glu Asp His Phe Tyr Gly Lys Gly Ile Ser Tyr130 135 140Cys Ala Ile Cys Asp Gly Ser Leu Tyr Lys Asp Gln Val Val Gly Val145 150 155 160Val Gly Gly Gly Asn Ser Ala Ile Gln Glu Ala Leu Tyr Leu Ala Ser165 170 175Met Ala Lys Thr Val His Leu Ile His Arg Arg Glu Gly Phe Arg Ala180 185 190Asp Glu Thr Ala Leu Asn Lys Leu Arg Asn Leu Pro Asn Val Val Phe195 200 205His Leu Asn Tyr Thr Val Lys Glu Leu Leu Gly Asn Asn Thr Leu Asn210 215 220Gly Ile Val Leu Gln Asn Thr Leu Asp His Ser Thr Lys Gln Ile Asp225 230 235 240Leu Asn Cys Val Phe Pro Tyr Ile Gly Phe Glu Ser Ile Thr Lys Pro245 250 255Val Glu His Leu Asn Leu Lys Leu Asp Pro Gln Gly Phe Leu Ile Thr260 265 270Asn Glu Gln Met Glu Thr Ser Leu Lys Gly Leu Phe Ala Ala Gly Asp275 280 285Cys Arg Ser Lys His Phe Arg Gln Ile Gly Thr Ala Ile Asn Asp Gly290 295 300Ile Ile Ala Val Leu Thr Ile Arg Asp Val Leu305 310 315210216211311212PRT213恥垢分枝桿菌400216Met Ser Thr Ser Gln Thr Val His Asp Val Ile Ile Ile Gly Ser Gly1 5 10 15Pro Ala Gly Tyr Thr Ala Ala Ile Tyr Ala Ala Arg Ala Gln Leu Lys20 25 30Pro Leu Val Phe Glu Gly Thr Gln Phe Gly Gly Ala Leu Met Thr Thr35 40 45Thr Glu Val Glu Asn Tyr Pro Gly Phe Arg Glu Gly Ile Thr Gly Pro50 55 60Glu Leu Met Asp Gln Met Arg Glu Gln Ala Leu Arg Phe Arg Ala Asp65 70 75 80Leu Arg Met Glu Asp Val Asp Ala Val Gln Leu Glu Gly Pro Val Lys85 90 95Thr Val Val Val Gly Asp Glu Thr His Gln Ala Arg Ala Val Ile Leu100 105 110Ala Met Gly Ala Ala Ala Arg His Leu Gly Val Pro Gly Glu Glu Ala115 120 125Leu Thr Gly Met Gly Val Ser Thr Cys Ala Thr Cys Asp Gly Phe Phe130 135 140Phe Arg Asp Gln Asp Ile Val Val Val Gly Gly Gly Asp Ser Ala Met145 150 155160Glu Glu Ala Thr Phe Leu Thr Arg Phe Ala Arg Ser Val Thr Leu Ile165 170 175His Arg Arg Asp Glu Phe Arg Ala Ser Lys Ile Met Leu Glu Arg Ala180 185 190Arg Ala Asn Glu Lys Ile Thr Phe Leu Thr Asn Thr Glu Ile Thr Gln195 200 205Ile Glu Gly Asp Pro Lys Val Thr Gly Val Arg Leu Arg Asp Thr Val210 215 220Thr Gly Glu Glu Ser Lys Leu Asp Val Thr Gly Val Phe Val Ala Ile225 230 235 240Gly His Asp Pro Arg Ser Glu Leu Val Arg Gly Gln Val Glu Leu Asp245 250 255Asp Glu Gly Tyr Val Lys Val Gln Gly Arg Thr Thr Tyr Thr Ser Leu260 265 270Asp Gly Val Phe Ala Ala Gly Asp Leu Val Asp His Thr Tyr Arg Gln275 280 285Ala Ile Thr Ala Ala Gly Ser Gly Cys Ala Ala Ser Ile Asp Ala Glu290 295 300Arg Trp Leu Ala Glu Gln Asp305 310210217211335212PRT213結核分枝桿菌400217Met Thr Ala Pro Pro Val His Asp Arg Ala His His Pro Val Arg Asp1 5 10 15Val Ile Val Ile Gly Ser Gly Pro Ala Gly Tyr Thr Ala Ala Leu Tyr20 25 30Ala Ala Arg Ala Gln Leu Ala Pro Leu Val Phe Glu Gly Thr Ser Phe35 40 45Gly Gly Ala Leu Met Thr Thr Thr Asp Val Glu Asn Tyr Pro Gly Phe50 55 60Arg Asn Gly Ile Thr Gly Pro Glu Leu Met Asp Glu Met Arg Glu Gln65 70 75 80Ala Leu Arg Phe Gly Ala Asp Leu Arg Met Glu Asp Val Glu Ser Val85 90 95Ser Leu His Gly Pro Leu Lys Ser Val Val Thr Ala Asp Gly Gln Thr100 105 110His Arg Ala Arg Ala Val Ile Leu Ala Met Gly Ala Ala Ala Arg Tyr115 120 125Leu Gln Val Pro Gly Glu Gln Glu Leu Leu Gly Arg Gly Val Ser Ser130 135 140Cys Ala Thr Cys Asp Gly Phe Phe Phe Arg Asp Gln Asp Ile Ala Val145 150 155 160Ile Gly Gly Gly Asp Ser Ala Met Glu Glu Ala Thr Phe Leu Thr Arg165 170 175Phe Ala Arg Ser Val Thr Leu Val His Arg Arg Asp Glu Phe Arg Ala180 185 190Ser Lys Ile Met Leu Asp Arg Ala Arg Asn Asn Asp Lys Ile Arg Phe195 200 205Leu Thr Asn His Thr Val Val Ala Val Asp Gly Asp Thr Thr Val Thr210 215 220Gly Leu Arg Val Arg Asp Thr Asn Thr Gly Ala Glu Thr Thr Leu Pro225 230 235 240Val Thr Gly Val Phe Val Ala Ile Gly His Glu Pro Arg Ser Gly Leu245 250 255Val Arg Glu Ala Ile Asp Val Asp Pro Asp Gly Tyr Val Leu Val Gln260 265 270Gly Arg Thr Thr Ser Thr Ser Leu Pro Gly Val Phe Ala Ala Gly Asp275 280 285Leu Val Asp Arg Thr Tyr Arg Gln Ala Val Thr Ala Ala Gly Ser Gly290 295 300Cys Ala Ala Ala Ile Asp Ala Glu Arg Trp Leu Ala Glu His Ala Ala305 310 315 320Thr Gly Glu Ala Asp Ser Thr Asp Ala Leu Ile Gly Ala Gln Arg325 330 335210218211334212PRT213粗糙鏈孢黴400218Met His Ser Lys Val Val Ile Ile Gly Ser Gly Pro Ala Ala His Thr1 5 10 15Ala Ala Ile Tyr Leu Ala Arg Ala Glu Leu Lys Pro Val Leu Tyr Glu20 25 30Gly Phe Met Ala Asn Gly Ile Ala Ala Gly Gly Gln Leu Thr Thr Thr35 40 45Thr Glu Ile Glu Asn Phe Pro Gly Phe Pro Asp Gly Ile Met Gly Gln50 55 60Glu Leu Met Asp Lys Met Lys Ala Gln Ser Glu Arg Phe Gly Thr Gln65 70 75 80Ile Ile Ser Glu Tnr Val Ala Lys Val Asp Leu Ser Ala Arg Pro Phe85 90 95Lys Tyr Ala Thr Glu Trp Ser Pro Glu Glu Tyr His Thr Ala Asp Ser100 105 110Ile Ile Leu Ala Thr Gly Ala Ser Ala Arg Arg Leu His Leu Pro Gly115 120 125Glu Glu Lys Tyr Trp Gln Asn Gly Ile Ser Ala Cys Ala Val Cys Asp130 135 140Gly Ala Val Pro Ile Phe Arg Asn Lys His Leu Val Val Ile Gly Gly145 150 155 160Gly Asp Ser Ala Ala Glu Glu Ala Met Tyr Leu Thr Lys Tyr Gly Ser165 170 175His Val Thr Val Leu Val Arg Lys Asp Lys Leu Arg Ala Ser Ser Ile180 185 190Met Ala His Arg Leu Leu Asn His Glu Lys Val Thr Val Arg Phe Asn195 200 205Thr Val Gly Val Glu Val Lys Gly Asp Asp Lys Gly Leu Met Ser His210 215 220Leu Val Val Lys Asp Val Thr Thr Gly Lys Glu Glu Thr Leu Glu Ala225 230 235 240Asn Gly Leu Phe Tyr Ala Ile Gly His Asp Pro Ala Thr Ala Leu Val245 250 255Lys Gly Gln Leu Glu Thr Asp Ala Asp Gly Tyr Val Val Thr Lys Pro260 265 270Gly Thr Thr Leu Thr Ser Val Glu Gly Val Phe Ala Ala Gly Asp Val275 280 285Gln Asp Lys Arg Tyr Arg Gln Ala Ile Thr Ser Ala Gly Thr Gly Cys290 295 300Met Ala Ala Leu Asp Ala Glu Lys Phe Leu Ser Glu His Glu Glu Thr305 310 315 320Pro Ala Glu His Arg Asp Thr Ser Ala Val Gln Gly Asn Leu325 330210219211333212PRT213產黃青黴400219Val His Ser Lys Val Val Ile Ile Gly Ser Gly Ala Gly Ala His Thr1 5 10 15Ala Ala Ile Tyr Leu Ser Arg Ala Glu Leu Gln Pro Val Leu Tyr Glu20 25 30Gly Met Leu Ala Asn Gly Thr Ala Ala Gly Gly Gln Leu Thr Thr Thr35 40 45Thr Asp Val Glu Asn Phe Pro Gly Phe Pro Ser Gly Ile Gly Gly Ala50 55 60Glu Leu Met Asp Asn Met Arg Ala Gln Ser Glu Arg Phe Gly Thr Glu65 70 75 80Ile Ile Thr Glu Thr Ile Ser Lys Leu Asp Leu Ser Ser Arg Pro Phe85 90 95Lys Met Trp Thr Glu Trp Asn Asp Asp Glu Gly Ser Glu Pro Val Arg100 105 110Thr Ala Asp Ala Val Ile Ile Ala Thr Gly Ala Asn Ala Arg Arg Leu115 120 125Asn Leu Pro Gly Glu Glu Thr Tyr Trp Gln Asn Gly Ile Ser Ala Cys130 135 140Ala Val Cys Asp Gly Ala Val Pro Ile Phe Arg Asn Lys Pro Leu Tyr145 150 155 160Val Ile Gly Gly Gly Asp Ser Ala Ala Glu Glu Ala Met Phe Leu Ala165 170 175Lys Tyr Gly Ser Ser Val Thr Val Leu Val Arg Lys Asp Lys Leu Arg180 185 190Ala Ser Asn Ile Met Ala Asp Arg Leu Leu Ala His Pro Lys Cys Lys195 200 205Val Arg Phe Asn Thr Val Ala Thr Glu Val Ile Gly Glu Asn Lys Pro210 215 220Asn Gly Leu Met Thr His Leu Arg Val Lys Asp VaI Leu Ser Asn Ala225 230 235 240Glu Glu Val Val Glu Ala Asn Gly Leu Phe Tyr Ala Val Gly His Asp245 250 255Pro Ala Ser Gly Leu Val Lys Gly Gln Val Glu Leu Asp Asp Glu Gly260 265 270Tyr Ile Ile Thr Lys Pro Gly Thr Ser Phe Thr Asn Val Glu Gly Val275 280 285Phe Ala Cys Gly Asp Val Gln Asp Lys Arg Tyr Arg Gln Ala Ile Thr290 295 300Ser Ala Gly Ser Gly Cys Val Ala Ala Leu Glu Ala Glu Lys Phe Ile305 310 315 320Ala Glu Thr Glu Thr His Gln Glu Ala Lys Pro Val Leu325 330210220211310212PRT213普魯畫斯克氏立克次氏體400220Met Lys Ile Thr Thr Lys Val Leu Ile Ile Gly Ser Gly Pro Ala Gly1 5 10 15Leu Ser Ala Ala Ile Tyr Thr Ala Arg Ser Ala Leu Lys Pro Ile Leu20 25 30Ile Asn Gly Met Gln Pro Gly Gly Gln Leu Thr Met Thr Thr Asp Val35 40 45Glu Asn Tyr Pro Gly Phe Ala Glu Thr Ile Gln Gly Pro Trp Leu Met50 55 60Glu Gln Met Ser Met Gln Ala Lys Asn Val Gly Thr Glu Ile Ile Ser65 70 75 80Asp Tyr Val Glu Arg Val Asp Leu Ser Lys Arg Pro Phe Lye Ile Phe85 90 95Thr Gly Thr Gly Asn Glu Tyr Glu Ala Asp Ser Ile Ile Ile Cys Thr100 105 110Gly Ala Glu Ser Lys Trp Leu Gly Ile Ala Ser Glu Gln Glu Phe Arg115 120 125Gly Phe Gly Val Ser Ser Cys Ala Ile Cys Asp Gly Phe Phe Phe Lys130 135 140Asn Gln Glu Ile Val Val Val Gly Gly Gly Asn Ser Ala Leu Glu Glu145 150 155 160Ala Leu Tyr Leu Thr Asn His Ala Asn Lys Val Thr Val Val His Arg165 170 175Arg Asn Ser Phe Arg Ala Glu Lys Ile Leu Gln Asp Arg Leu Phe Lys180 185 190Asn Pro Lys Ile Ser Val Ile Trp Asp His Ile Ile Asp Glu Ile Val
195 200 205Gly Ser Asn Lys Pro Lys Ala Val Thr Gly Val Lys Ile Gln Asn Val210 215 220Tyr Thr Asn Glu Ile Asn Leu Val Asn Cys Ser Gly Val Phe Ile Ala225 230 235 240Ile Gly His Ala Pro Asn Thr Ala Leu Phe Lys Gly Gln Ile Ala Ile245 250 255Asp Asp Asp Asn Tyr Ile Val Thr Gln Ser Gly Ser Thr Arg Thr Asn260 265 270Val Glu Gly Val Phe Ala Ala Gly Asp Val Gln Asp Lys Ile Tyr Arg275 280 285Gln Ala Val Thr Ala Ala Ala Ser Gly Cys Met Ala Ala Leu Glu Val290 295 300Ala Lys Phe Leu Asn Lys305 310210221211322212PRT213粟酒裂殖糖酵母400221Met Thr His Asn Lys Val Val Ile Ile Gly Ser Gly Pro Ala Gly His1 5 10 15Thr Ala Ala Ile Tyr Leu Ala Arg Gly Glu Leu Lys Pro Val Met Tyr20 25 30Glu Gly Met Leu Ala Asn Gly Ile Ala Ala Gly Gly Gln Leu Thr Thr35 40 45Thr Thr Asp Val Glu Asn Phe Pro Gly Phe Pro Asp Gly Ile Asn Gly50 55 60Thr Thr Leu Thr Glu Asn Phe Arg Ala Gln Ser Leu Arg Phe Gly Thr65 70 75 80Glu Ile Ile Thr Glu Thr Val Ser Lys Leu Asp Leu Ser Ser Arg Pro85 90 95Phe Lys Tyr Trp Leu Glu Gly Ala Glu Glu Glu Glu Pro His Thr Ala100 105 110Asp Ser Val Ile Leu Ala Thr Gly Ala Ser Ala Arg Arg Leu His Ile115 120 125Thr Gly Glu Asp Thr Tyr Trp Gln Ala Gly Ile Ser Ala Cys Ala Val130 135 140Cys Asp Gly Ala Val Pro Ile Tyr Arg Asn Lys Pro Leu Ala Val Val145 150 155 160Gly Gly Gly Asp Ser Ala Ala Glu Glu Ala Gln Phe Leu Thr Lys Tyr165 170 175Gly Ser Lys Val Tyr Val Leu Val Arg Arg Asp Lys Leu Arg Ala Ser180 185 190Pro Ile Met Ala Lys Arg Leu Leu Ala Asn Pro Lys Val Glu Val Leu195 200 205Trp Asn Thr Val Ala Glu Glu Ala Gln Gly Asp Gly Lys Leu Leu Asn210 215 220Asn Leu Arg Ile Lys Asn Thr Asn Thr Asn Glu Val Ser Asp Leu Gln225 230 235 240Val Asn Gly Leu Phe Tyr Ala Ile Gly His Ile Pro Ala Thr Lys Leu245 250 255Val Ala Glu Gln Ile Glu Leu Asp Glu Ala Gly Tyr Ile Lys Thr Ile260 265 270Asn Gly Thr Pro Arg Thr Ser Ile Pro Gly Phe Phe Ala Ala Gly Asp275 280 285Val Gln Asp Lys Val Phe Arg Gln Ala Ile Thr Ser Ala Gly Ser Gly290 295 300Cys Gln Ala Ala Leu Leu Ala Met His Tyr Leu Glu Glu Leu Glu Asp305 310 315 320Thr Asp210222211321212PRT213帶棒鏈黴菌400222Ser Asp Val Arg Asn Val Ile Ile Ile Gly Ser Gly Pro Ala Gly Tyr1 5 10 15Thr Ala Ala Leu Tyr Thr Ala Arg Ala Ser Leu Gln Pro Leu Val Phe20 25 30Glu Gly Ala Val Thr Ala Gly Gly Ala Leu Met Asn Thr Thr Asp Val35 40 45Glu Asn Phe Pro Gly Phe Arg Asp Gly Ile Met Gly Pro Asp Leu Met50 55 60Asp Asn Met Arg Ala Gln Ala Glu Arg Phe Gly Ala Glu Leu Ile Pro65 70 75 80Asp Asp Val Val Ser Val Asp Leu Thr Gly Asp Ile Lys Thr Val Thr85 90 95Asp Ser Ala Gly Thr Val His Arg Ala Lys Ala Val Ile Val Thr Thr100 105 110Gly Ser Gln His Arg Lys Leu Gly Leu Pro Arg Glu Asp Ala Leu Ser115 120 125Gly Arg Gly Val Ser Trp Cys Ala Thr Cys Asp Gly Phe Phe Phe Lys130 135 140Asp Gln Asp Ile Val Val Val Gly Gly Gly Asp Thr Ala Met Glu Glu145 150 155 160Ala Thr Phe Leu Ser Arg Phe Ala Lys Ser Val Thr Ile Val His Arg165 170 175Arg Asp Ser Leu Arg Ala Ser Lys Ala Met Gln Asp Arg Ala Phe Ala180 185 190Asp Pro Lys Ile Ser Phe Ala Trp Asn Ser Glu Val Ala Thr Ile His195 200 205Gly Glu Gln Lys Leu Thr Gly Leu Thr Leu Arg Asp Thr Lys Thr Gly210 215 220Glu Thr Arg Glu Leu Ala Ala Thr Gly Leu Phe Ile Ala Val Gly His225 230 235 240Asp Pro Arg Thr Glu Leu Phe Lys Gly Gln Leu Asp Leu Asp Asp Glu245 250 255Gly Tyr Leu Lys Val Ala Ser Pro Ser Thr Arg Thr Asn Leu Thr Gly260 265 270Val Phe Ala Ala Gly Asp Val Val Asp His Thr Tyr Arg Gln Ala Ile275 280 285Thr Ala Ala Gly Thr Gly Cys Ser Ala Ala Leu Asp Ala Glu Arg Tyr290 295 300Leu Ala Ala Leu Ala Asp Ser Glu Gln Ile Ala Glu Pro Ala Pro Ala305 310 315 320Val210223211321212PRT213天藍色鏈黴菌400223Ser Asp Val Arg Asn Val Ile Ile Ile Gly Ser Gly Pro Ala Gly Tyr1 5 10 15Thr Ala Ala Leu Tyr Thr Ala Arg Ala Ser Leu Lys Pro Leu Val Phe20 25 30Glu Gly Ala Val Thr Ala Gly Gly Ala Leu Met Asn Thr Thr Glu Val35 40 45Glu Asn Phe Pro Gly Phe Gln Asp Gly Ile Met Gly Pro Glu Leu Met50 55 60Asp Asn Met Arg Ala Gln Ala Glu Arg Phe Gly Ala Glu Leu Ile Pro65 70 75 80Asp Asp Val Val Ala Val Asp Leu Ser Gly Glu Ile Lys Thr Val Thr
85 90 95Asp Thr Ala Gly Thr Val His Arg Ala Lys Ala Val Ile Val Thr Thr100 105 110Gly Ser Gln His Arg Lys Leu Gly Leu Pro Asn Glu Asp Ala Leu Ser115 120 125Gly Arg Gly Val Ser Trp Cys Ala Thr Cys Asp Gly Phe Phe Phe Lys130 135140Asp Gln Asp Ile Ala Val Ile Gly Gly Gly Asp Thr Ala Met Glu Glu145 150 155 160Ala Thr Phe Leu Ser Arg Phe Ala Lys Ser Val Thr Ile Val His Arg165 170 175Arg Asp Thr Leu Arg Ala Ser Lys Ala Met Gln Glu Arg Ala Phe Ala180 185 190Asp Pro Lys Ile Ser Phe Val Trp Asp Ser Glu Val Ala Glu Val Gln195 200 205Gly Asp Gln Lys Leu Ala Gly Leu Lys Leu Arg Asn Val Lys Thr Gly210 215 220Glu Leu Ser Asp Leu Pro Val Thr Gly Leu Phe Ile Ala Ile Gly His225 230 235 240Asp Pro Arg Thr Glu Leu Phe Lys Gly Gln Leu Asp Leu Asp Pro Glu245 250 255Gly Tyr Leu Lys Val Asp Ala Pro Ser Thr Arg Thr Asn Leu Thr Gly260 265 270Val Phe Gly Ala Gly Asp Val Val Asp His Thr Tyr Arg Gln Ala Ile275 280 285Thr Ala Ala Gly Thr Gly Cys Ser Ala Ala Val Asp Ala Glu Pro Phe290 295 300Leu Ala Ala Leu Ser Asp Glu Asp Lys Ala Glu Pro Glu Lys Thr Ala305 310 315 320Val210224211307212PRT213蒼白密螺旋體400224Met Glu Thr Asp Tyr Asp Val Ile Ile Val Gly Ala Gly Ala Ala Gly1 5 10 15Leu Ser Ala Ala Gln Tyr Ala Cys Arg Ala Asn Leu Arg Thr Leu Val20 25 30Ile Glu Ser Lys Ala His Gly Gly Gln Ala Leu Leu Ile Asp Ser Leu35 40 45Glu Asn Tyr Pro Gly Tyr Ala Thr Pro Ile Ser Gly Phe Glu Tyr Ala50 55 60Glu Asn Met Lys Lys Gln Ala Val Ala Phe Gly Ala Gln Ile Ala Tyr65 70 75 80Glu Glu Val Thr Thr Ile Gly Lys Arg Asp Ser Val Phe His Ile Thr85 90 95Thr Gly Thr Gly Ala Tyr Thr Ala Met Ser Val Ile Leu Ala Thr Gly100 105 110Ala Glu His Arg Lys Met Gly Ile Pro Gly Glu Ser Glu Phe Leu Gly115 120 125Arg Gly Val Ser Tyr Cys Ala Thr Cys Asp Gly Pro Phe Phe Arg Asn130 135 140Lys His Val Val Val Ile Gly Gly Gly Asp Ala Ala Cys Asp Glu Ser145 150 155 160Leu Val Leu Ser Arg Leu Thr Asp Arg Val Thr Met Ile His Arg Arg165 170 175Asp Thr Leu Arg Ala Gln Lys Ala Ile Ala Glu Arg Thr Leu Lys Asn180 185 190Pro His Ile Ala Val Gln Trp Asn Thr Thr Leu Glu Ala Val Arg Gly195 200 205Glu Thr Lys Val Ser Ser Val Leu Leu Lys Asp Val Lys Thr Gly Glu210 215 220Thr Arg Glu Leu Ala Cys Asp Ala Val Phe Phe Phe Ile Gly Met Val225 230 235 240Pro Ile Thr Gly Leu Leu Pro Asp Ala Glu Lys Asp Ser Thr Gly Tyr245 250 255Ile Val Thr Asp Asp Glu Met Arg Thr Ser Val Glu Gly Ile Phe Ala260 265 270Ala Gly Asp Val Arg Ala Lys Ser Phe Arg Gln Val Ile Thr Ala Thr275 280 285Ser Asp Gly Ala Leu Ala Ala His Ala Ala Ala Ser Tyr Ile Asp Thr290 295 300Leu Gln Asn30521022521145212PRT213費氏弧菌400225Met Asn Val Lys His Ser Lys Leu Leu Ile Leu Gly Ser Gly Pro Ala1 5 10 15Gly Tyr Thr Ala Ala Val Tyr Ala Ala Arg Ala Asn Leu Asn Pro Val20 25 30Met Ile Thr Gly Met Gln Gln Gly Gly Gln Leu Thr Asn35 40 45210226211318212PRT213啤酒糖酵母400226Val His Asn Lys Val Thr Ile Ile Gly Ser Gly Pro Ala Ala His Thr1 5 10 15Ala Ala Ile Tyr Leu Ala Arg Ala Glu Ile Lys Pro Ile Leu Tyr Glu20 25 30Gly Met Met Ala Asn Gly Ile Ala Ala Gly Gly Gln Leu Thr Thr Thr35 40 45Thr Glu Ile Glu Asn Phe Pro Gly Phe Pro Asp Gly Leu Thr Gly Ser50 55 60Glu Leu Met Asp Arg Met Arg Glu Gln Ser Thr Lys Phe Gly Thr Glu65 70 75 80Ile Ile Thr Glu Thr Val Ser Lys Val Asp Leu Ser Ser Lys Pro Phe85 90 95Lys Leu Trp Thr Glu Phe Asn Glu Asp Ala Glu Pro Val Thr Thr Asp100 105 110Ala Ile Ile Leu Ala Thr Gly Ala Ser Ala Lys Arg Met His Leu Pro115 120 125Gly Glu Glu Thr Tyr Trp Gln Lys Gly Ile Ser Ala Cys Ala Val Cys130 135 140Asp Gly Ala Val Pro Ile Phe Arg Asn Lys Pro Leu Ala Val Ile Gly145 150 155 160Gly Gly Asp Ger Ala Cys Glu Glu Ala Gln Phe Leu Thr Lys Tyr Gly165 170 175Ser Lys Val Phe Met Leu Val Arg Lys Asp His Leu Arg Ala Ser Thr180 185 190Ile Met Gln Lys Arg Ala Glu Lys Asn Glu Lys Ile Glu Ile Leu Tyr195 200 205Asn Thr Val Ala Leu Glu Ala Lys Gly Asp Gly Lys Leu Leu Asn Ala210 215 220Leu Arg Ile Lys Asn Thr Lys Lys Asn Glu Glu Thr Asp Leu Pro Val225 230 235 240Ser Gly Leu Phe Tyr Ala Ile Gly His Thr Pro Ala Thr Lys Ile Val245 250 255Ala Gly Gln Val Asp Thr Asp Glu Ala Gly Tyr Ile Lys Thr Val Pro
260 265 270Gly Ser Ser Leu Thr Ser Val Pro Gly Phe Phe Ala Ala Gly Asp Val275 280 285Gln Asp Ser Lys Tyr Arg Gln Ala Ile Thr Ser Ala Gly Ser Gly Cys290 295 300Met Ala Ala Leu Asp Ala Glu Lys Tyr Leu Thr Ser Leu Glu305 310 315210227211342212PRT213啤酒糖酵母400227Met Ile Lys His Ile Val Ser Pro Phe Arg Thr Asn Phe Val Gly Ile1 5 10 15Ser Lys Ser Val Leu Ser Arg Met Ile His His Lys Val Thr Ile Ile20 25 30Gly Ser Gly Pro Ala Ala His Thr Ala Ala Ile Tyr Leu Ala Arg Ala35 40 45Glu Met Lys Pro Thr Leu Tyr Glu Gly Met Met Ala Asn Gly Ile Ala50 55 60Ala Gly Gly Gln Leu Thr Thr Thr Thr Asp Ile Glu Asn Phe Pro Gly65 70 75 80Phe Pro Glu Ser Leu Ser Gly Ser Glu Leu Met Glu Arg Met Arg Lys85 90 95Gln Ser Ala Lys Phe Gly Thr Asn Ile Ile Thr Glu Thr Val Ser Lys100 105 110Val Asp Leu Ser Ser Lys Pro Phe Arg Leu Trp Thr Glu Phe Asn Glu115 120 125Asp Ala Glu Pro Val Thr Thr Asp Ala Ile Ile Leu Ala Thr Gly Ala130 135 140Ser Ala Lys Arg Met His Leu Pro Gly Glu Glu Thr Tyr Trp Gln Gln145 150 155 160Gly Ile Ser Ala Cys Ala Val Cys Asp Gly Ala Val Pro Ile Phe Arg165 170 175Asn Lys Pro Leu Ala Val Ile Gly Gly Gly Asp Ser Ala Cys Glu Glu180 185 190Ala Glu Phe Leu Thr Lys Tyr Ala Ser Lys Val Tyr Ile Leu Val Arg195 200 205Lys Asp His Phe Arg Ala Ser Val Ile Met Gln Arg Arg Ile Glu Lys210 215 220Asn Pro Asn Ile Ile Val Leu Phe Asn Thr Val Ala Leu Glu Ala Lys225 230 235 240Gly Asp Gly Lys Leu Leu Asn Met Leu Arg Ile Lys Asn Thr Lys Ser245 250 255Asn Val Glu Asn Asp Leu Glu Val Asn Gly Leu Phe Tyr Ala Ile Gly260 265 270His Ser Pro Ala Thr Asp Ile Val Lys Gly Gln Val Asp Glu Glu Glu275 280 285Thr Gly Tyr Ile Lys Thr Val Pro Gly Ser Ser Leu Thr Ser Val Pro290 295 300Gly Phe Phe Ala Ala Gly Asp Val Gln Asp Ser Arg Tyr Arg Gln Ala305 310 315 320Val Thr Ser Ala Gly Ser Gly Cys Ile Ala Ala Leu Asp Ala Glu Arg325 330 335Tyr Leu Ser Ala Gln Glu340210228211499212PRT213Bos taurus400228Met Asn Gly Ser Lys Asp Leu Pro Glu Pro Tyr Asp Tyr Asp Leu Ile1 5 10 15Ile Ile Gly Gly Gly Ser Gly Gly Leu Ala Ala Ala Lys Glu Ala Ala20 25 30Lys Tyr Asp Lys Lys Val Met Val Leu Asp Phe Val Thr Pro Thr Pro35 40 45Leu Gly Thr Arg Trp Gly Leu Gly Gly Thr Cys Val Asn Val Gly Cys50 55 60Ile Pro Lys Lys Leu Met His Gln Ala Ala Leu Leu Gly Gln Ala Leu65 70 75 80Arg Asp Ser Arg Asn Tyr Gly Trp Asn Val Glu Glu Thr Val Lys His85 90 95Asp Trp Glu Arg Met Thr Glu Ala Val Gln Asn His Ile Gly Ser Leu100 105 110Asn Trp Gly Tyr Arg Val Ala Leu Arg Glu Lys Lys Val Thr Tyr Glu115 120 125Asn Ala Tyr Gly Glu Phe Val Gly Pro His Arg Ile Lys Ala Thr Asn130 135 140Asn Lys Gly Lys Glu Lys Ile Tyr Ser Ala Glu Arg Phe Leu Ile Ala145 150 155 160Thr Gly Glu Arg Pro Arg Tyr Leu Gly Ile Pro Gly Asp Lys Glu Tyr165 170 175Cys Ile Ser Ser Asp Asp Leu Phe Ser Leu Pro Tyr Cys Pro Gly Lys180 185 190Thr Leu Val Val Gly Ala Ser Tyr Val Ala Leu Glu Cys Ala Gly Phe195 200 205Leu Ala Gly Ile Gly Leu Asp Val Thr Val Met Val Arg Ser Ile Leu210 215 220Leu Arg Gly Phe Asp Gln Asp Met Ala Asn Lys Ile Gly Glu His Met225 230 235 240Gln Glu His Gly Ile Lys Phe Ile Arg Gln Phe Val Pro Ile Lys Val245 250 255Glu Gln Ile Glu Ala Gly Thr Pro Gly Arg Leu Arg Val Ile Ala Lys260 265 270Ser Thr Asp Ser Asp Gln Thr Ile Glu Gly Glu Tyr Asn Thr Val Leu275 280 285Leu Ala Ile Gly Arg Asp Ala Cys Thr Arg Lys Ile Gly Leu Glu Asn290 295 300Val Gly Val Lys Ile Asn Glu Lys Thr Gly Lys Ile Pro Val Thr Glu305 310 315 320Glu Glu Gln Thr Asn Val Pro Tyr Ile Tyr Ala Ile Gly Asp Ile Leu325 330 335Glu Gly Lys Leu Glu Leu Thr Pro Val Ala Ile Gln Ala Gly Arg Leu340 345 350Leu Ala Gln Arg Leu Tyr Gly Gly Ser Thr Val Lys Cys Asp Tyr Glu355 360 365Asn Val Pro Thr Thr Val Phe Thr Pro Leu Glu Tyr Gly Ser Cys Gly370 375 380Leu Ser Glu Glu Lys Ala Val Glu Lys Phe Gly Glu Glu Asn Val Glu385 390 395 400Val Tyr His Ser Tyr Phe Trp Pro Leu Glu Trp Thr Ile Pro Ser Arg405 410 415Asp Asn Asn Lys Cys Tyr Ala Lys Val Val Cys Asn Ile Lys Asp Asn420 425 430Glu Arg Val Val Gly Phe His Val Leu Gly Pro Asn Ala Gly Glu Val435 440 445Thr Gln Gly Phe Ala Ala Ala Leu Lys Cys Gly Leu Thr Lys Asp Gln450 455 460Leu Asp Ser Thr Ile Gly Ile His Pro Val Cys Ala Glu Val Phe Thr465 470 475 480Thr Leu Ser Val Thr Lys Arg Ser Gly Gly Asn Ile Leu Gln Thr Gly485 490 495Cys Cys Gly210229211523212PRT213Caenorhabditis elegans400229Met Tyr Ile Lys Gly Asn Ala Val Gly Gly Leu Lys Glu Leu Lys Ala1 5 10 15Leu Lys Gln Asp Tyr Leu Lys Glu Trp Leu Arg Asp His Thr Tyr Asp20 25 30Leu Ile Val Ile Gly Gly Gly Ser Gly Gly Leu Ala Ala Ala Lys Glu35 40 45Ala Ser Arg Leu Gly Lys Lys Val Ala Cys Leu Asp Phe Val Lys Pro50 55 60Ser Pro Gln Gly Thr Ser Trp Gly Leu Gly Gly Thr Cys Val Asn Val65 70 75 80Gly Cys Ile Pro Lys Lys Leu Met His Gln Ala Ser Leu Leu Gly His85 90 95Ser Ile His Asp Ala Lys Lys Tyr Gly Trp Lys Leu Pro Glu Gly Lys100 105 110Val Glu His Gln Trp Asn His Leu Arg Asp Ser Val Gln Asp His Ile115 120 125Ala Ser Leu Asn Trp Gly Tyr Arg Val Gln Leu Arg Glu Lys Thr Val130 135 140Thr Tyr Ile Asn Ser Tyr Gly Glu Phe Thr Gly Pro Phe Glu Ile Ser145 150 155 160Ala Thr Asn Lys Lys Lys Lys Val Glu Lys Leu Thr Ala Asp Arg Phe165 170 175Leu Ile Ser Thr Gly Leu Arg Pro Lys Tyr Pro Glu Ile Pro Gly Val180 185 190Lys Glu Tyr Thr Ile Thr Ser Asp Asp Leu Phe Gln Leu Pro Tyr Ser195 200 205Pro Gly Lys Thr Leu Cys Val Gly Ala Ser Tyr Val Ser Leu Glu Cys210 215 220Ala Gly Phe Leu His Gly Phe Gly Phe Asp Val Thr Val Met Val Arg225 230 235 240Ser Ile Leu Leu Arg Gly Phe Asp Gln Asp Met Ala Glu Arg Ile Arg245 250 255Lys His Met Ile Ala Tyr Gly Met Lys Phe Glu Ala Gly Val Pro Thr260 265 270Arg Ile Glu Gln Ile Asp Glu Lys Thr Asp Glu Lys Ala Gly Lys Tyr275 280 285Arg Val Phe Trp Pro Lys Lys Asn Glu Glu Thr Gly Glu Met Gln Glu290 295 300Val Ser Glu Glu Tyr Asn Thr Ile Leu Met Ala Ile Gly Arg Glu Ala305 310 315 320Val Thr Asp Asp Val Gly Leu Thr Thr Ile Gly Val Glu Arg Ala Lys325 330 335Ser Lys Lys Val Leu Gly Arg Arg Glu Gln Ser Thr Thr Ile Pro Trp340 345 350Val Tyr Ala Ile Gly Asp Val Leu Glu Gly Thr Pro Glu Leu Thr Pro355 360 365Val Ala Ile Gln Ala Gly Arg Val Leu Met Arg Arg Ile Phe Asp Gly370 375 380Ala Asn Glu Leu Thr Glu Tyr Asp Gln Ile Pro Thr Thr Val Phe Thr385 390 395 400Pro Leu Glu Tyr Gly Cys Cys Gly Leu Ser Glu Glu Asp Ala Met Met405 410 415Lys Tyr Gly Lys Asp Asn Ile Ile Ile Tyr His Asn Val Phe Asn Pro420 425 430Leu Glu Tyr Thr Ile Ser Glu Arg Met Asp Lys Asp His Cys Tyr Leu435 440 445Lys Met Ile Cys Leu Arg Asn Glu Glu Glu Lys Val Val Gly Phe His450 455 460Ile Leu Thr Pro Asn Ala Gly Glu Val Thr Gln Gly Phe Gly Ile Ala465 470 475 480Leu Lys Leu Ala Ala Lys Lys Ala Asp Phe Asp Arg Leu Ile Gly Ile485 490 495His Pro Thr Val Ala Glu Asn Phe Thr Thr Leu Thr Leu Glu Lys Lys500 505 510Glu Gly Asp Glu Glu Leu Gln Ala Ser Gly Cys515 520210230211497212PRT213人400230Met Asn Gly Pro Glu Asp Leu Pro Lys Ser Tyr Asp Tyr Asp Leu Ile1 5 10 15Ile Ile Gly Gly Gly Ser Gly Gly Leu Ala Ala Ala Lys Glu Ala Ala20 25 30Gln Tyr Gly Lys Lys Val Met Val Leu Asp Phe Val Thr Pro Thr Pro35 40 45Leu Gly Thr Arg Trp Gly Leu Gly Gly Thr Cys Val Asn Val Gly Cys50 55 60Ile Pro Lys Lys Leu Met His Gln Ala Ala Leu Leu Gly Gln Ala Leu65 70 75 80Gln Asp Ser Arg Asn Tyr Gly Trp Lys Val Glu Glu Thr Val Lys His85 90 95Asp Trp Asp Arg Met Ile Glu Ala Val Gln Asn His Ile Gly Ser Leu100 105 110Asn Trp Gly Tyr Arg Val Ala Leu Arg Glu Lys Lys Val Val Tyr Glu115 120 125Asn Ala Tyr Gly Gln Phe Ile Gly Pro His Arg Ile Lys Ala Thr Asn130 135 140Asn Lys Gly Lys Glu Lys Ile Tyr Ser Ala Glu Ser Phe Leu Ile Ala145 150 155 160Thr Gly Glu Arg Pro Arg Tyr Leu Gly Ile Pro Gly Asp Lys Glu Tyr165 170 175Cys Ile Ser Ser Asp Asp Leu Phe Ser Leu Pro Tyr Cys Pro Gly Lys180 185 190Thr Leu Val Val Gly Ala Ser Tyr Val Ala Leu Glu Cys Ala Gly Phe195 200 205Leu Ala Gly Ile Gly Leu Gly Val Thr Val Met Val Arg Ser Ile Leu210 215 220Leu Arg Gly Phe Asp Gln Asp Met Ala Asn Lys Ile Gly Glu His Met225 230 235 240Glu Glu His Gly Ile Lys Phe Ile Arg Gln Phe Val Pro Ile Lys Val245 250 255Glu Gln Ile Glu Ala Gly Thr Pro Gly Arg Leu Arg Val Val Ala Gln260 265 270Ser Thr Asn Ser Glu Glu Ile Ile Glu Gly Glu Tyr Asn Thr Val Met275 280 285Leu Ala Ile Gly Arg Asp Ala Cys Thr Arg Lys Ile Gly Leu Glu Thr290 295 300Val Gly Val Lys Ile Asn Glu Lys Thr Gly Lys Ile Pro Val Thr Asp305 310 315 320Glu Glu Gln Thr Asn Val Pro Tyr Ile Tyr Ala Ile Gly Asp Ile Leu325 330 335Glu Asp Lys Val Glu Leu Thr Pro Val Ala Ile Gln Ala Gly Arg Leu340 345 350Leu Ala Gln Arg Leu Tyr Ala Gly Ser Thr Val Lys Cys Asp Tyr Glu355 360 365Asn Val Pro Thr Thr Val Phe Thr Pro Leu Glu Tyr Gly Ala Cys Gly370 375 380Leu Ser Glu Glu Lys Ala Val Glu Lys Phe Gly Glu Glu Asn Ile Glu385 390 395 400Val Tyr His Ser Tyr Phe Trp Pro Leu Glu Trp Thr Ile Pro Ser Arg405 410 415Asp Asn Asn Lys Cys Tyr Ala Lys Ile Ile Cys Asn Thr Lys Asp Asn420 425 430Glu Arg Val Val Gly Phe His Val Leu Gly Pro Asn Ala Gly Glu Val
435 440 445Thr Gln Gly Phe Ala Ala Ala Leu Lys Cys Gly Leu Thr Lys Lys Gln450 455 460Leu Asp Ser Thr Ile Gly Ile His Pro Val Cys Ala Glu Val Phe Thr465 470 475 480Thr Leu Ser Val Thr Lys Arg Ser Gly Ala Ser Ile Leu Gln Ala Gly485 490 495Cys210231211541212PRT213Plasmodium falciparum400231Met Cys Lys Asp Lys Asn Glu Lys Lys Asn Tyr Glu His Val Asn Ala1 5 10 15Asn Glu Lys Asn Gly Tyr Leu Ala Ser Glu Lys Asn Glu Leu Thr Lys20 25 30Asn Lys Val Glu Glu His Thr Tyr Asp Tyr Asp Tyr Val Val Ile Gly35 40 45Gly Gly Pro Gly Gly Met Ala Ser Ala Lys Glu Ala Ala Ala His Gly50 55 60Ala Arg Val Leu Leu Phe Asp Tyr Val Lys Pro Ser Ser Gln Gly Thr65 70 75 80Lys Trp Gly Ile Gly Gly Thr Cys Val Asn Val Gly Cys Val Pro Lys85 90 95Lys Leu Met His Tyr Ala Gly His Met Gly Ser Ile Phe Lys Leu Asp100 105 110Ser Lys Ala Tyr Gly Trp Lys Phe Asp Asn Leu Lys His Asp Trp Lys115 120 125Lys Leu Val Thr Thr Val Gln Ser His Ile Arg Ser Leu Asn Phe Ser130 135 140Tyr Met Thr Gly Leu Arg Ser Ser Lys Val Lys Tyr Ile Asn Gly Leu145 150 155 160Ala Lys Leu Lys Asp Lys Asn Thr Val Ser Tyr Tyr Leu Lys Gly Asp165 170 175Leu Ser Lys Glu Glu Thr Val Thr Gly Lys Tyr Ile Leu Ile Ala Thr180 185 190Gly Cys Arg Pro His Ile Pro Asp Asp Val Glu Gly Ala Lys Glu Leu195 200 205Ser Ile Thr Ser Asp Asp Ile Phe Ser Leu Lys Lys Asp Pro Gly Lys210 215 220Thr Leu Val Val Gly Ala Ser Tyr Val Ala Leu Glu Cys Ser Gly Phe225 230 235 240Leu Asn Ser Leu Gly Tyr Asp Val Thr Val Ala Val Arg Ser Ile Val245 250 255Leu Arg Gly Phe Asp Gln Gln Cys Ala Val Lys Val Lys Leu Tyr Met260 265 270Glu Glu Gln Gly Val Met Phe Lys Asn Gly Ile Leu Pro Lys Lys Leu275 280 285Thr Lys Met Asp Asp Lys Ile Leu Val Glu Phe Ser Asp Lys Thr Ser290 295 300Glu Leu Tyr Asp Thr Val Leu Tyr Ala Ile Gly Arg Lys Gly Asp Ile305 310 315 320Asp Gly Leu Asn Leu Glu Ser Leu Asn Met Asn Val Asn Lys Ser Asn325 330 335Asn Lys Ile Ile Ala Asp His Leu Ser Cys Thr Asn Ile Pro Ser Ile340 345 350Phe Ala Val Gly Asp Val Ala Glu Asn Val Pro Glu Leu Ala Pro Val355 360 365Ala Ile Lys Ala Gly Glu Ile Leu Ala Arg Arg Leu Phe Lys Asp Ser370 375 380Asp Glu Ile Met Asp Tyr Ser Tyr Ile Pro Thr Ser Ile Tyr Thr Pro385 390 395 400Ile Glu Tyr Gly Ala Cys Gly Tyr Ser Glu Glu Lys Ala Tyr Glu Leu405 410 415Tyr Gly Lys Ser Asn Val Glu Val Phe Leu Gln Glu Phe Asn Asn Leu420 425 430Glu Ile Ser Ala Val His Arg Gln Lys His Ile Arg Ala Gln Lys Asp435 440 445Glu Tyr Asp Leu Asp Val Ser Ser Thr Cys Leu Ala Lys Leu Val Cys450 455 460Leu Lys Asn Glu Asp Asn Arg Val Ile Gly Phe His Tyr Val Gly Pro465 470 475 480Asn Ala Gly Glu Val Thr Gln Gly Met Ala Leu Ala Leu Arg Leu Lys485 490 495Val Lys Lys Lys Asp Phe Asp Asn Cys Ile Gly Ile His Pro Thr Asp500 505 510Ala Glu Ser Phe Met Asn Leu Phe Val Thr Ile Ser Ser Gly Leu Ser515 520 525Tyr Ala Ala Lys Gly Gly Cys Gly Gly Gly Lys Cys Gly530 535 540210232211535212PRT213鼠耳芥400232Met Ala Ala Ser Pro Lys Ile Gly Ile Gly Ile Ala Ser Val Ser Ser1 5 10 15Pro His Arg Val Ser Ala Ala Ser Ser Ala Leu Ser Pro Pro Pro His20 25 30Leu Phe Phe Leu Thr Thr Thr Thr Thr Thr Arg His Gly Gly Ser Tyr35 40 45Leu Leu Arg Gln Pro Thr Arg Thr Arg Ser Ser Asp Ser Leu Arg Leu50 55 60Arg Val Ser Ala Thr Ala Asn Ser Pro Ser Ser Ser Ser Ser Gly Gly65 70 75 80Glu Ile Ile Glu Asn Val Val Ile Ile Gly Ser Gly Pro Ala Gly Tyr85 90 95Thr Ala Ala Ile Tyr Ala Ala Arg Ala Asn Leu Lys Pro Val Val Phe100 105 110Glu Gly Tyr Gln Met Gly Gly Val Pro Gly Gly Gln Leu Met Thr Thr115 120 125Thr Glu Val Glu Asn Phe Pro Gly Phe Pro Asp Gly Ile Thr Gly Pro130 135 140Asp Leu Met Glu Lys Met Arg Lys Gln Ala Glu Arg Trp Gly Ala Glu145 150 155 160Leu Tyr Pro Glu Asp Val Glu Ser Leu Ser Val Thr Thr Ala Pro Phe165 170 175Thr Val Gln Thr Ser Glu Arg Lys Val Lys Cys His Ser Ile Ile Tyr180 185 190Ala Thr Gly Ala Thr Ala Arg Arg Leu Arg Leu Pro Arg Glu Glu Glu195 200 205Phe Trp Ser Arg Gly Ile Ser Ala Cys Ala Ile Cys Asp Gly Ala Ser210 215 220Pro Leu Phe Lys Gly Gln Val Leu Ala Val Val Gly Gly Gly Asp Thr225 230 235 240Ala Thr Glu Glu Ala Leu Tyr Leu Thr Lys Tyr Ala Arg His Val His245 250 255Leu Leu Val Arg Arg Asp Gln Leu Arg Ala Ser Lys Ala Met Gln Asp260 265 270Arg Val Ile Asn Asn Pro Asn Ile Thr Val His Tyr Asn Thr Glu Thr275 280 285Val Asp Val Leu Ser Asn Thr Lys Gly Gln Met Ser Gly Ile Leu Leu290 295 300Arg Arg Leu Asp Thr Gly Glu Glu Thr Glu Leu Glu Ala Lys Gly Leu305 310 315 320Phe Tyr Gly Ile Gly His Ser Pro Asn Ser Gln Leu Leu Glu Gly Gln
325 330 335Val Glu Leu Asp Ser Ser Gly Tyr Val Leu Val Arg Glu Gly Thr Ser340 345 350Asn Thr Ser Val Glu Gly Val Phe Ala Ala Gly Asp Val Gln Asp His355 360 365Glu Trp Arg Gln Ala Val Thr Ala Ala Gly Ser Gly Cys Ile Ala Ala370 375 380Leu Ser Ala Glu Arg Tyr Leu Thr Ser Asn Asn Leu Leu Val Glu Phe385 390 395 400His Gln Pro Gln Thr Glu Glu Ala Lys Lys Glu Phe Thr Gln Arg Asp405 410 415Val Gln Glu Lys Phe Asp Ile Thr Leu Thr Lys His Lys Gly Gln Tyr420 425 430Ala Leu Arg Lys Leu Tyr His Glu Ser Pro Arg Val Ile Leu Val Leu435 440 445Tyr Thr Ser Pro Thr Cys Gly Pro Cys Arg Thr Leu Lys Pro Ile Leu450 455 460Asn Lys Val Val Asp Glu Tyr Asn His Asp Val His Phe Val Glu Ile465 470 475 480Asp Ile Glu Glu Asp Gln Glu Ile Ala Glu Ala Ala Gly Ile Mer Gly485 490 495Thr Pro Cys Val Gln Phe Phe Lys Asn Lys Glu Mer Leu Arg Leu Gly500 505 510Asn Val Leu Ser Val Leu Lys Leu His Arg Leu Leu Cys Ser Gly Leu515 520 525Ala Lys Asp Ser Glu Ser Val530 535210233211117212PRT213向日葵400233Ala Val Val Glu Ala Tyr Gly Glu Glu Gly Lys Asn Val Leu Gly Gly1 5 10 15Leu Lys Val Lys Asn Val Val Ser Gly Glu Val Ser Asp Leu Lys Val20 25 30Asn Gly Leu Phe Phe Ala Ile Gly His Glu Pro Ala Thr Lys Phe Leu35 40 45Asp Gly Gln Leu Glu Leu Asp Ser Asp Gly Tyr Val Val Thr Lys Pro50 55 60Gly Thr Thr Ile Ser Ser Val Lys Gly Val Phe Ala Ala Gly Asp Val65 70 75 80Gln Asp Lys Lys Tyr Arg Gln Ala Val Thr Ala Ala Gly Ser Gly Cys85 90 95Met Ala Ala Leu Asp Ala Glu His Tyr Leu Gln Glu Ile Gly Ser Gln100 105 110Glu Gly Lys Ser Asp115210234211300212PRT213閃爍古生球菌400234Met Tyr Asp Val Ala Ile Ile Gly Gly Gly Pro Ala Gly Leu Thr Ala1 5 10 15Ala Leu Tyr Ser Ala Arg Tyr Gly Leu Lys Thr Val Phe Phe Glu Thr20 25 30Val Asp Pro Val Ser Gln Leu Ser Leu Ala Ala Lys Ile Glu Asn Tyr35 40 45Pro Gly Phe Glu Gly Ser Gly Met Glu Leu Leu Glu Lys Met Lys Glu50 55 60Gln Ala Val Lys Ala Gly Ala Glu Trp Lys Leu Glu Lys Val Glu Arg65 70 75 80Val Glu Arg Asn Gly Glu Thr Phe Thr Val Ile Ala Glu Gly Gly Glu85 90 95Tyr Glu Ala Lys Ala Ile Ile Val Ala Thr Gly Gly Lys His Lys Glu100 105 110Ala Gly Ile Glu Gly Glu Ser Ala Phe Ile Gly Arg Gly Val Ser Tyr115 120 125Cys Ala Thr Cys Asp Gly Asn Phe Phe Arg Gly Lys Lys Val Ile Val130 135 140Tyr Gly Ser Gly Lys Glu Ala Ile Glu Asp Ala Ile Tyr Leu His Asp145 150 155 160Ile Gly Cys Glu Val Thr Ile Val Ser Arg Thr Pro Ser Phe Arg Ala165 170 175Glu Lys Ala Leu Val Glu Glu Val Glu Lys Arg Gly Ile Pro Val His180 185 190Tyr Ser Thr Thr Ile Arg Lys Ile Ile Gly Ser Gly Lys Val Glu Lys195 200 205Val Val Ala Tyr Asn Arg Glu Lys Lys Glu Glu Phe Glu Ile Glu Ala210 215 220Asp Gly Ile Phe Val Ala Ile Gly Met Arg Pro Ala Thr Asp Val Val225 230 235 240Ala Glu Leu Gly Val Glu Arg Asp Ser Met Gly Tyr Ile Lys Val Asp245 250 255Lys Glu Gln Arg Thr Asn Val Glu Gly Val Phe Ala Ala Gly Asp Cys260 265 270Cys Asp Asn Pro Leu Lys Gln Val Val Thr Ala Cys Gly Asp Gly Ala275 280 285Val Ala Ala Tyr Ser Ala Tyr Lys Tyr Leu Thr Ser290 295300210235211315212PRT213Bacillus halodurans400235Met Gly Glu Glu Gln Lys Val Tyr Asp Val Val Ile Ala Gly Ala Gly1 5 10 15Pro Ala Gly Met Thr Ala Ala Val Tyr Thr Ser Arg Ala Asn Leu Ser20 25 30Thr Val Met Val Glu Arg Gly Val Pro Gly Gly Gln Met Ala Asn Thr35 40 45Glu Asp Val Glu Asn Tyr Pro Gly Phe Asp His Ile Leu Gly Pro Glu50 55 60Leu Ser Thr Lys Met Phe Glu His Ala Lys Lys Phe Gly Ala Glu Tyr65 70 75 80Ala Tyr Gly Asp Ile Lys Glu Ile Ile Asp Gln Gly Asp Leu Lys Leu85 90 95Val Lys Ala Gly Asn Lys Glu Tyr Lys Ala Arg Ala Val Ile Val Ala100 105 110Thr Gly Ala Glu Tyr Lys Lys Leu Gly Val Pro Gly Glu Lys Glu Leu115 120 125Ser Gly Arg Gly Val Ser Tyr Cys Ala Val Cys Asp Gly Ala Phe Phe130 135 140Lys Gly Lys Glu Leu Val Val Val Gly Gly Gly Asp Ser Ala Val Glu145 150 155 160Glu Ala Val Tyr Leu Thr Arg Phe Ala Ser Lys Val Thr Ile Ile His165 170 175Arg Arg Asp Gln Leu Arg Ala Gln Lys Ile Leu Gln Gln Arg Ala Phe180 185 190Asp Asn Asp Lys Ile Glu Phe Ile Trp Asp His Val Val Lys Gln Ile195 200 205Asn Gly Thr Asp Gly Lys Val Ser Ser Val Thr Ile Glu His Ala Lys210 215 220Thr Gly Glu Gln Gln Asp Phe Lys Thr Asp Gly Val Phe Ile Tyr Ile225 230 235 240Gly Met Leu Pro Leu Asn Glu Ala Val Lys Asn Leu Asn Ile Leu Asn245 250 255Asp Glu Gly Tyr Ile Val Thr Asn Glu Glu Met Glu Thr Ser Val Pro260 265 270Gly Ile Phe Ala Ala Gly Asp Val Arg Glu Lys Ser Leu Arg Gln Ile275 280 285Val Thr Ala Thr Gly Asp Gly Ser Leu Ala Ala Gln Asn Val Gln His290 295 300Tyr Ile Glu Glu Leu Ala Glu Lys Val Lys Asn305 310 315210236211330212PRT213Bacillus halodurans400236Met Ser Arg Lys Glu Glu Leu Tyr Asp Ile Thr Ile Ile Gly Gly Gly1 5 10 15Pro Thr Gly Leu Phe Ala Ala Phe Tyr Gly Gly Met Arg Gln Ala Lys20 25 30Val Lys Ile Ile Glu Ser Met Pro Gln Leu Gly Gly Gln Leu Ala Ala35 40 45Leu Tyr Pro Glu Lys Tyr Ile Tyr Asp Val Ala Gly Phe Pro Lys Val50 55 60Lys Ala Gln Asp Leu Val Asn Asp Leu Lys Arg Gln Ala Glu Gln Phe65 70 75 80Asn Pro Thr Ile Ala Leu Glu Gln Ser Val Gln Asn Val Thr Lys Glu85 90 95Thr Asp Asp Thr Phe Thr Ile Lys Thr Asp Lys Glu Thr His Tyr Ser100 105 110Lys Ala Ile Ile Ile Thr Ala Gly Ala Gly Ala Phe Gln Pro Arg Arg115 120 125Leu Glu Val Glu Gly Ala Lys Gln Tyr Glu Gly Lys Asn Leu Gln Tyr130 135 140Phe Val Asn Asp Leu Asn Ala Tyr Ala Gly Lys Asn Val Leu Ile Ser145 150 155 160Gly Gly Gly Asp Ser Ala Val Asp Trp Ala Leu Met Leu Glu Pro Val165 170 175Ala Lys Asn Val Thr Leu Ile His Arg Arg Asp Lys Phe Arg Ala His180 185 190Glu His Ser Val Glu Leu Leu Gln Lys Ser Ser Val Asn Ile Leu Thr195 200 205Pro Phe Ala Ile Ser Glu Leu Ser Gly Asp Gly Glu Lys Ile His His210 215 220Val Thr Ile Gln Glu Val Lys Gly Asp Ala Val Glu Thr Leu Asp Val225 230 235 240Asp Glu Val Ile Val Asn Phe Gly Phe Val Ser Ser Leu Gly Pro Ile245 250 255Lys Gly Trp Gly Leu Glu Ile Glu Lys Asn Ser Ile Val Val Asn Thr260 265 270Lys Met Glu Thr Asn Ile Pro Gly Ile Tyr Ala Ala Gly Asp Ile Cys275 280 285Thr Tyr Pro Gly Lys Val Lys Leu Ile Ala Thr Gly Phe Gly Glu Ala290 295 300Pro Thr Ala Val Asn Asn Ala Lys Ala Phe Ile Asp Pro Thr Ala Arg305 310 315 320Val Phe Pro Gly His Ser Thr Ser Leu Phe325 330210237211213212PRT213Bacillus halodurans400237Met Thr Asn Leu His Tyr Thr Val Lys Ser Leu Met Arg Phe Lys Asp1 5 10 15Lys Thr Val Ile Ile Ser Gly Gly Gly Asn Ser Ala Ile Asp Trp Ala20 25 30Asn Glu Leu Glu Pro Ile Ala Lys Lys Val Tyr Leu Thr Tyr Arg Lys35 40 45Glu Ala Leu Asn Gly His Glu Ala Gln Ile Ser Gln Leu Leu Ser Ser50 55 60Ser Ala Thr Cys Leu Phe His Thr Thr Ile Ser Lys Leu Ile Ala Arg65 70 75 80Asp Asn Lys Glu Val Ile Glu Gln Val Glu Leu Thr Asp His Gln Thr85 90 95Gly Glu Val Thr Asn Leu Ala Val Asp Glu Val Ile Ile Asn His Gly100 105 110Tyr Glu Arg Asp Lys Ser Leu Leu Asp Gln Ser Glu Val Thr Leu Asp115 120 125Arg Ile Asp Asp Tyr Tyr Ile Ala Gly Thr Pro Thr Ser Ala Thr Ser130 135 140Val Gly Gly Ile Tyr Ala Ala Gly Asp Val Leu Lys His Glu Gly Lys145 150 155 160Leu His Leu Ile Ala Gly Ala Phe Gln Asp Ala Ala Asn Ala Val Asn165 170 175Gln Ala Lys Gln Trp Ile Glu Pro Glu Ala His Gln Ser Ala Met Val180 185 190Ser Ser His Asn His Val Phe Lys Glu Arg Asn Arg Glu Leu Ile Arg195 200 205Gln Met Leu Lys Asn210210238211136212PRT213Bacillus halodurans400238Met Asn Trp Glu Glu Leu Tyr Asp Val Thr Ile Ile Gly Gly Gly Pro1 5 10 15Ala Gly Leu Phe Ser Ala Phe Tyr Ser Gly Leu Arg Glu Met Lys Thr20 25 30Lys Val Ile Glu Tyr Gln Pro Met Leu Gly Gly Lys Val His Val Tyr35 40 45Pro Glu Lys Met Ile Trp Asp Val Gly Gly Leu Thr Pro Ile Leu Gly50 55 60Glu Lys Leu Ile Glu Gln Leu Val Thr Gln Ala Leu Thr Phe Asn Pro65 70 75 80Thr Val Val Leu Asn Glu Lys Val Thr Ser Ile Ala Gln Glu Glu Ser85 90 95Gly Trp Phe Val Ile Arg Thr Ala Ser Gly Arg Ala His Leu Thr Lys100 105 110Thr Val Ile Ile Ala Val Gly Gly Gly Ile Leu Lys Pro Gln Lys Asn115 120 125Arg Ala Arg Arg Gly Arg Thr Ile130 135210239211312212PRT213空腸彎曲桿菌空腸亞種400239Met Leu Asp Val Ala Ile Ile Gly Gly Gly Pro Ala Gly Leu Ser Ala1 5 10 15Gly Leu Tyr Ala Thr Arg Gly Gly Leu Lys Asn Val Val Met Phe Glu20 25 30Lys Gly Met Pro Gly Gly Gln Ile Thr Ser Ser Ser Glu Ile Glu Asn35 40 45Tyr Pro Gly Val Ala Gln Val Met Asp Gly Ile Ser Phe Met Ala Pro50 55 60Trp Ser Glu Gln Cys Met Arg Phe Gly Leu Lys His Glu Met Val Gly65 70 75 80Val Glu Gln Ile Leu Lys Asn Ser Asp Gly Ser Phe Thr Ile Lys Leu85 90 95Glu Gly Gly Lys Thr Glu Leu Ala Lys Ala Val Ile Val Cys Thr Gly100 105 110Ser Ala Pro Lys Lys Ala Gly Phe Lys Gly Glu Asp Glu Phe Phe Gly115 120 125Lys Gly Val Ser Thr Cys Ala Thr Cys Asp Gly Phe Phe Tyr Lys Asn130 135 140Lys Glu Val Ala Val Leu Gly Gly Gly Asp Thr Ala Leu Glu Glu Ala145 150 155 160Leu Tyr Leu Ala Asn Ile Cys Ser Lys Ile Tyr Leu Ile His Arg Arg165 170 175Asp Glu Phe Arg Ala Ala Pro Ser Thr Val Glu Lys Val Lys Lys Asn180 185 190Glu Lys Ile Glu Leu Ile Thr Ser Ala Ser Val Asp Glu Val Tyr Gly195 200 205Asp Lys Met Gly Val Ala Gly Val Lys Val Lys Leu Lys Asp Gly Ser210 215 220Ile Arg Asp Leu Asn Val Pro Gly Ile Phe Thr Phe Val Gly Leu Asn225 230 235 240Val Arg Asn Glu Ile Leu Lys GlnAsp Asp Ser Lys Phe Leu Cys Asn245250 255Met Glu Glu Gly Gly Gln Val Ser Val Asp Leu Lys Met Gln Thr Ser260 265 270Val Ala Gly Leu Phe Ala Ala Gly Asp Leu Arg Lys Asp Ala Pro Lys275 280 285Gln Val Ile Cys Ala Ala Gly Asp Gly Ala Val Ala Ala Leu Ser Ala290 295 300Met Ala Tyr Ile Glu Ser Leu His305 310210240211348212PRT213新月柄桿菌400240Met Ser Pro Leu Arg Arg Ile His Thr Ile Ser Pro Pro Met Ser Thr1 5 10 15Leu Ser Pro Arg Gln Thr Arg Cys Leu Ile Ile Gly Ser Gly Pro Ala20 25 30Gly Tyr Thr Ala Ala Ile Tyr Ala Ala Arg Ala Leu Leu Lys Pro Val35 40 45Leu Ile Ala Gly Ile Gln Pro Gly Gly Gln Leu Thr Ile Thr Thr Asp50 55 60Val Glu Asn Tyr Pro Gly Phe Ala Asp Val Ile Gln Gly Pro Trp Leu65 70 75 80Met Asp Gln Met Arg Ala Gln Ala Glu His Val Gly Thr Glu Phe Val85 90 95Ser Asp Ile Val Thr Ser Val Asp Leu Ser Lys Arg Pro Phe Thr Val100 105 110Lys Thr Asp Ser Gly Gln Asp Trp Ile Ala Glu Thr Ile Ile Ile Ala115 120 125Thr Gly Ala Gln Ala Lys Trp Leu Gly Leu Glu Ser Glu Ala Lys Phe130 135 140Gln Gly Phe Gly Val Ser Ala Cys Ala Thr Cys Asp Gly Phe Phe Tyr145 150 155 160Arg Asn Lys Asp Val Ile Val Val Gly Gly Gly Asn Thr Ala Val Glu165 170 175Glu Ala Leu Phe Leu Thr Ser Phe Ala Ser Lys Val Thr Leu Val His
180 185 190Arg Lys Asp Glu Leu Arg Ala Glu Lys Ile Leu Gln Glu Arg Leu Leu195 200 205Ala His Pro Lys Ile Glu Val Ile Trp Asp Ser Val Ile Asp Glu Val210 215 220Leu Gly Gln Thr Asp Pro Met Gly Val Thr Gly Ala Arg Leu Lys Asn225 230 235 240Val Lys Thr Gly Glu Thr Gln Glu Val Ala Ala Asp Gly Val Phe Ile245 250 255Ala Ile Gly His Ala Pro Ser Ser Glu Leu Phe Ala Gly Gln Leu Glu260 265 270Thr Gly Ser Gly Gly Tyr Leu Lys Val Lys Pro Gly Thr Ala Ser Thr275 280 285Ala Ile Glu Gly Val Tyr Ala Ala Gly Asp Val Thr Asp Asp Val Tyr290 295 300Arg Gln Ala Val Thr Ala Ala Gly Met Gly Cys Met Ala Ala Leu Glu305 310 315 320Ala Val Arg Phe Leu Ala Glu Glu Asp His Lys Ala Ala His His Pro325 330 335Ile Ser His Ala Glu Ala Asn Lys Ile Gly Val Trp340 345210241211285212PRT213丙酮丁醇梭狀芽孢桿菌400241Met Glu Arg Tyr Asp Ile Ala Ile Ile Gly Ser Gly Pro Ala Gly Leu1 5 10 15Ala Ser Ala Ile Asn Ala Lys Thr Arg Asn Lys Ser Val Ile Val Phe20 25 30Gly Ser Ser Asp Leu Ser Lys Lys Leu Thr Leu Ala Pro Val Ile Asn35 40 45Asn Tyr Leu Gly Phe Tyr Gly Ile Arg Gly Ala Glu Leu Gln Glu Lys50 55 60Phe Lys Glu His Ile Asp Asn Met Gly Ile Gln Ile Glu Asn Val Lys65 70 75 80Val Asn Asn Ile Tyr Ala Met Gly Glu Tyr Phe Ser Ile Met Thr Ser85 90 95Lys Asp Thr Tyr Glu Ala Ser Lys Val Ile Leu Ala Met Gly Met Glu100 105 110His Thr Lys Pro Leu Lys Gly Glu Asp Lys Phe Leu Gly Arg Gly Val115 120 125Gly Tyr Cys Ala Thr Cys Asp Ala Pro Leu Tyr Lys Gly Lys Ile Val130 135 140Thr Ile Val Gly Tyr Asn Lys Glu Ala Glu Ser Glu Ala Asn Tyr Leu145 150 155 160Ala Glu Leu Ala Ser Lys Val Tyr Tyr Val Pro Arg Tyr Lys Asp Glu165 170 175Tyr Gln Leu Val Ser Ala Val Glu Ile Val Lys Asp Val Pro Val Glu180 185 190Ile Val Gly Asp Lys Lys Val Glu Lys Leu Lys Leu Lys Ser Arg Glu195 200 205Leu Glu Thr Asp Gly Val Phe Val Leu Lys Asp Ser Ala Pro Pro Glu210 215 220Gln Leu Val Pro Gly Leu Tyr Val Glu Asp Gly His Ile Lys Val Asn225 230 235 240Arg Lys Met Glu Thr Asn Ile Asp Gly Cys Tyr Ala Ala Gly Asp Cys245 250 255Thr Gly Lys Pro Tyr Gln Tyr Met Lys Ala Val Gly Glu Gly Gln Val260 265 270Ala Ala Leu Asn Ala Val Glu Lys Leu Tyr Thr Lys Ala275 280 285210242211291212PRT213丙酮丁醇梭狀芽孢桿菌400242Met Asp Arg Tyr Asp Ile Ala Ile Ile Gly Ser Gly Pro Ala Gly Leu1 5 10 15Ser Ala Ala Ile Asn Ala Val Ile Arg Asn Lys Lys Val Ile Leu Phe20 25 30Gly Ser Asp Asn Leu Ser Asn Lys Leu Leu Lys Ala Pro Lys Ile Asn35 40 45Asn Tyr Leu Gly Ile Tyr Asp Val Ser Gly Lys Glu Leu Lys Glu Lys50 55 60Phe Leu Glu His Leu Lys Tyr Met Asn Ile Glu Ile Lys Asn Glu Lys65 70 75 80Val Asn Ser Val Tyr Ser Met Gly Asp Tyr Phe Ala Leu Ser Leu Asn85 90 95Gln Lys Met Tyr Glu Ala Thr Ser Ile Ile Ile Ala Ser Gly Val Glu100 105 110Phe Ser Lys Pro Leu Asn Gly Glu Asp Glu Leu Leu Gly Lys Gly Val115 120 125Gly Tyr Cys Ala Thr Cys Asp Ala Pro Leu Tyr Lys Gly Lys Thr Val130 135 140Ala Ile Val Gly Tyr Thr Lys Glu Ala Glu Glu Glu Ala Asn Tyr Val145 150 155 160Ser Glu Leu Ala Gly Lys Leu Tyr Tyr Ile Pro Met Tyr Lys Asp Lys165 170 175Val Ser Leu Lys Glu Val Ile Glu Val Val Glu Asp Lys Pro Ile Ser180 185 190Ile Leu Gly Lys Asp Lys Val Ser Gly Leu Gln Met Ser Lys Gly Glu195 200 205Ile Asn Thr Asp Ala Val Phe Ile Ile Lys Asp Ser Val Ser Pro Gly210 215 220Lys Leu Val Pro Gly Leu Leu Met Asn Gly Glu His Ile Ala Val Asp225 230 235 240Ile Asp Met Lys Thr Asn Ile Glu Gly Cys Phe Ala Ala Gly Asp Cys245 250 255Ala Gly Arg Pro Tyr Gln Tyr Ile Lys Ser Ala Gly Gln Gly Gln Ile260 265 270Ala Ala Leu Ser Ala Val Ser Tyr Ile Asp Lys Ile Lys Leu Asn Lys275 280 285Lys Ile Ile290210243211314212PRT213斯蒂克蘭德氏梭狀芽孢桿菌400243Met Ser Lys Ile Tyr Asp Leu Val Ile Ile Gly Ala Gly Pro Ala Gly1 5 10 15Leu Ser Ala Gly Leu Tyr Gly Ala Arg Gly Lys Met Ser Thr Leu Ile20 25 30Ile Glu Lys Asp Lys Thr Gly Gly Gln Ile Val Thr Thr Glu Glu Val35 40 45Ala Asn Tyr Pro Gly Ser Ile His Asp Ala Ser Gly Pro Ser Leu Ile50 55 60Ala Arg Met Ala Glu Gln Ala Asp Glu Phe Gly Thr Glu Arg Ile Lys65 70 75 80Asp Ser Ile Val Asp Phe Asp Phe Thr Gly Lys Ile Lys Ile Leu Lys85 90 95Gly Thr Lys Ala Glu Tyr Gln Ala Lys Ala Val Ile Val Ala Thr Gly100 105 110Ala Ser Pro Lys Lys Leu Asp Cys Pro Gly Glu Lys Glu Leu Thr Gly
115 120 125Lys Gly Val Ser Tyr Cys Ala Thr Cys Asp Ala Asp Phe Phe Gln Asp130 135 140Met Glu Val Phe Val Val Gly Gly Gly Asp Ser Ala Val Glu Glu Ala145 150 155 160Met Tyr Leu Thr Lys Phe Ala Ser Lys Val Thr Ile Val His Arg Arg165 170 175Asp Ser Leu Arg Ala Ala Lys Ser Ile Gln Asp Lys Ala Phe Ala Asn180 185 190Pro Lys Ile Asp Phe Lys Trp Asp Ser Val Ile Lys Glu Ile Lys Gly195 200 205Asp Gly Ile Val Glu Ser Val Val Phe Glu Asn Thr Lys Thr Gly Glu210 215 220Leu Ser Glu His Phe Ala Asp Glu Glu Phe Gly Thr Phe Gly Ile Phe225 230 235 240Val Phe Thr Gly Tyr Ile Pro Gln Thr Asp Ile Phe Lys Asp Lys Val245 250 255Asp Met Asn Gln Ser Gly Tyr Phe Val Thr Asn Gln Asn Met Glu Thr260 265 270Asn Ile Pro Gly Val Phe Ala Ala Gly Asp Cys Arg Glu Lys Val Leu275 280 285Arg Gln Val Val Thr Ala Thr Ala Asp Gly Ala Ile Ala Ala Ile Met290 295 300Ala Glu Lys Tyr Ile Glu His Glu Gly Leu305 310210244211325212PRT213耐放射異常球菌400244Met Thr Ala Pro Thr Ala His Asp Tyr Asp Val Val Ile Ile Gly Gly1 5 10 15Gly Pro Ala Gly Leu Thr Ala Ala Ile Tyr Thr Gly Arg Ala Gln Leu20 25 30Ser Thr Leu Ile Leu Glu Lys Gly Met Pro Gly Gly Gln Ile Ala Trp35 40 45Ser Glu Glu Val Glu Asn Phe Pro Gly Phe Pro Glu Pro Ile Ala Gly50 55 60Met Glu Leu Ala Gln Arg Met His Gln Gln Ala Glu Lys Phe Gly Ala65 70 75 80Lys Val Glu Met Asp Glu Val Gln Gly Val Gln His Asp Ala Thr Ser85 90 95His Pro Tyr Pro Phe Thr Val Arg Gly Tyr Asn Gly Glu Tyr Arg Ala100 105110Lys Ala Val Ile Leu Ala Thr Gly Ala Asp Pro Arg Lys Leu Gly Ile115 120 125Pro Gly Glu Asp Asn Phe Trp Gly Lys Gly Val Ser Thr Cys Ala Thr130 135 140Cys Asp Gly Phe Phe Tyr Lys Gly Lys Lys Val Val Val Ile Gly Gly145 150 155 160Gly Asp Ala Ala Val Glu Glu Gly Met Phe Leu Thr Lys Phe Ala Asp165 170 175Glu Val Thr Val Ile His Arg Arg Asp Thr Leu Arg Ala Asn Lys Val180 185 190Ala Gln Ala Arg Ala Phe Ala Asn Pro Lys Met Lys Phe Ile Trp Asp195 200 205Thr Ala Val Glu Glu Ile Gln Gly Ala Asp Ser Val Ser Gly Val Lys210 215 220Leu Arg Asn Leu Lys Thr Gly Glu Val Ser Glu Leu Ala Thr Asp Gly225 230 235 240Val Phe Ile Phe Ile Gly His Val Pro Asn Thr Ala Phe Val Lys Asp245 250 255Thr Val Ser Leu Arg Asp Asp Gly Tyr Val Asp Val Arg Asp Glu Ile260 265 270Tyr Thr Asn Ile Pro Met Leu Phe Ala Ala Gly Asp Val Ser Asp Tyr275 280 285Ile Tyr Arg Gln Leu Ala Thr Ser Val Gly Ala Gly Thr Arg Ala Ala290 295 300Met Met Thr Glu Arg Gln Leu Ala Ala Leu Glu Val Glu Gly Glu Glu305 310 315 320Val Thr Ala Ala Asp32521024521161212PRT213糞腸球菌220221VARIANT22233，45，46223Xaa＝任何胺基酸400245Met Met Asp Thr Leu Ile Ile Glu Lys Asp Lys Ile Gly Gly Gln Val1 5 10 15Thr Thr Thr Ser Glu Ile Val Asn Tyr Pro Ala Ile Arg His Thr Thr20 25 30Xaa Pro Glu Leu Met Gly Glu Met Arg Ile Gln Ala Xaa Xaa Phe Gly35 40 45Val Ala Phe Thr Lys Asp Glu Ile Ile Asp Val Asp Phe50 55 60210246211205212PRT213鹽桿菌屬400246Met Thr Glu Asp Ser His Asp Leu Val Ile Ala Gly Ser Gly Ile Ala1 5 10 15Gly Leu Ser Ala Ala Val Tyr Ala Ala Arg Ala Asp Leu Glu Pro Leu20 25 30Val Leu Glu Gly Asp Glu Pro Gly Gly Gln Leu Thr Leu Thr Thr Asp35 40 45Val Glu Asn Tyr Leu Gly Phe Pro Asp Gly Val Gly Gly Met Asp Leu50 55 60Val Gln Arg Gly Lys Glu Gln Ala Glu Gln Phe Gly Ala Gln Phe Glu65 70 75 80His Gly Arg Ile Glu Ala Ala Asp Leu Asp Gly Gln Pro Leu Glu Leu85 90 95Ser Leu Ser Thr Gly Asp Thr Leu Tyr Thr Arg Ser Leu Ile Val Ala100 105 110Thr Gly Ala Ser Ala Arg Trp Val Gly Ala Glu Asn Glu Asp Glu Leu115 120 125Met Gly Ala Gly Leu Ser Thr Cys Ala Thr Cys Asp Gly Ala Phe His130 135 140Arg Gly Asp Asp Val Leu Val Val Gly Gly Gly Asp Ser Ala Met Glu145 150 155 160Glu Ala Leu Phe Leu Ala Lys Phe Ala Asp Ser Val Thr Val Val His165 170 175Arg Arg Glu Glu Leu Arg Ala Ser Glu Ile Met Ala Asp Arg Ala Arg180 185 190Asp His Asp Asp Val Gln Phe Arg Trp Asn Thr Glu Leu195 200 205210247211362212PRT213鹽桿菌屬400247Met Thr Glu Ala Thr Ala Asp Arg Thr Ala Leu Thr Asp Gly Gly Arg1 5 10 15Asp Val Val Glu His Arg Gln Leu Val Ile Val Gly Ser Gly Ile Ala20 25 30Ala Leu Ser Ala Ala Thr Tyr Ala Ala Arg Ser Asn Asn Asp Pro Leu35 40 45Leu Phe Glu Gly Asp Glu Pro Gly Gly Gln Leu Thr Leu Thr Ser Glu50 55 60Val Glu Asn Tyr Pro Gly Phe Pro Glu Gly Ile Ala Gly Ala Glu Leu65 70 75 80Ile Gln Glu Met Lys Thr Gln Ala Thr Arg Phe Gly Ala Glu Val Glu85 90 95His Gly Ile Val Glu Ser Val Asp Asp Ser Gly Arg Pro Phe ArG Leu100 105 110Thr Leu Thr Asn Gly Asp Val Tyr Thr Ala Asp Ala Val Ile Val Ala115 120 125Ser Gly Ala Ser Ala Arg Thr Leu Gly Ile Pro Gly Glu Asp Glu Leu130 135 140Met Gly Gln Gly Val Ser Thr Cys Ala Thr Cys Asp Gly Ala Phe Phe145 150 155 160Arg Gly Glu Asp Met Ile Val Val Gly Gly Gly Asp Ala Ala Ala Glu165 170 175Glu Ala Ser Phe Leu Thr Lys Phe Ala Asp Thr Val Tyr Leu Val His180 185 190Arg Arg Asp Glu Leu Arg Ala Glu Asp Tyr Trp Ala Asp Arg Ile Arg195 200 205Glu His Val Ala Asp Gly Asp Ile Glu Val Leu Trp Asn Thr Glu Ala210 215 220Val Glu Val His Gly Ser Pro Glu Glu Gly Val Thr Gly Ala Ser Leu225 230 235 240Val Arg His Pro Glu Gly His Pro Thr Ala Lys Leu Asp Ala Asp Glu245 250 255Thr Glu Gln Leu Glu Leu Asp Ile Gly Ala Phe Phe Ile Ala Ile Gly260 265 270His Thr Pro Asn Thr Ser Phe Leu Ala Asp Thr Gly Val Val Cys Asp275 280 285Asp Ala Gly Tyr Val Gln Thr Val Gly Gly Ala Gly Gly Gly Gln Thr290 295 300Lys Thr Asp Val Thr Gly Val Phe Gly Ala Gly Asp Val Val Asp Tyr305 310 315 320His Tyr Gln Gln Ala Val Thr Ala Ala Gly Met Gly Ser Lys Ala Ala325 330 335Ile Asp Ala Asp Glu Tyr Leu Glu Ser Val Ala Asp Gly Val Thr Gly340 345 350Glu Thr Ala Asp Ala Thr Pro Ala Asp Asp355 360210248211294212PRT213鹽桿菌屬400248Met Pro Thr Gln Asp Gly Glu Arg Arg Asp Val Val Ile Val Gly Gly1 5 10 15Gly Pro Ala Gly Cys Ala Ala Gly Val Phe Thr Ala Arg Tyr Gly Leu20 25 30Asp Thr Val Val Phe Asp Arg Gly Asn Ala Ala Leu Pro Arg Cys Ala35 40 45Phe Val Glu Asn Tyr Pro Gly Phe Pro Gly Gly Ile Asp Val Pro Thr50 55 60Leu Arg Gly Leu Phe His Asp His Ala Glu Thr Ala Gly Cys Asp Leu65 70 75 80Ile Ala Asp Thr Val Glu Ser Val Asp Arg Pro Ser Asp Asp Asp Thr85 90 95Gly Phe Val Val Glu Thr Gln Asp Gly Arg Arg Val Tyr Thr Asp Thr100 105 110Val Leu Ala Ala Ala Trp Tyr Asp Gly Ser Tyr Leu Arg Pro Val Val115 120 125Gly Asp Ser Ala Phe Glu Thr His Asp His His Gly Glu Ser Arg Glu130 135140Arg Phe Asp Asp Ala Tyr Ala Asp Ala Asp Gly Arg Thr Pro Val Asp145 150 155 160Gly Leu Tyr Val Ala Ser Pro Gly Gly Gln Arg Ser Ala Gln Ala Val165 170 175Ile Ala Ala Gly Asn Gly Ala His Val Ala Arg Cys Leu Leu Ala Asp180 185 190Arg Lys Arg Ala Arg Gly Tyr Pro Glu Gly Val Ala Pro His Tyr Asp195 200 205Trp Lys Arg Arg Glu Ser Asp Leu Ser Gly Glu Trp Ala Asp Arg Asp210 215 220Arg Trp Arg Glu Trp Phe Ala Ala Glu Ala Gly Asp Asp His Asp Leu225 230 235 240Asp Asp Asp Glu Phe Ala Ala Leu Arg Ala Ala His Leu Asp Arg Thr245 250 255Phe Asp Ala Thr Leu Ser Ala Asp Ala Ile Glu Glu Arg Ala Glu Ala260 265 270Gly Ala His Arg Leu Leu Asp His Ile Asp Asp Asp His Ile Glu Ser275 280 285Tyr Arg Glu Gln Arg Asp290210249211324212PRT213幽門螺桿菌400249Met Asn Gln Glu Ile Leu Asp Val Leu Ile Val Gly Ala Gly Pro Gly1 5 10 15Gly Ile Ala Thr Ala Val Glu Cys Glu Ile Ala Gly Val Lys Lys Val20 25 30Leu Leu Cys Glu Lys Thr Glu Ser His Ser Gly Met Leu Glu Lys Phe35 40 45Tyr Lys Ala Gly Lys Arg Ile Asp Lys Asp Tyr Lys Lys Gln Val Val50 55 60Glu Leu Lys Gly His Ile Pro Phe Lys Asp Ser Phe Lys Glu Glu Thr65 70 75 80Leu Glu Asn Phe Thr Asn Leu Leu Lys Glu His His Ile Thr Pro Ser85 90 95Tyr Lys Thr Asp Ile Glu Ser Val Lys Lys Glu Gly Glu Tyr Phe Lys100 105 110Ile Thr Thr Thr Ser Asn Thr Thr Tyr His Ala Lys Phe Val Val Val115 120 125Ala Ile Gly Lys Met Gly Gln Pro Asn Arg Pro Thr Ala Tyr Lys Ile130 135 140Pro Val Ala Leu Ser Lys Gln Val Val Phe Ser Ile Asn Asp Cys Lys145 150 155 160Glu Asn Glu Lys Thr Leu Val Ile Gly Gly Gly Asn Ser Ala Val Glu165 170 175Tyr Ala Ile Ala Leu Cys Lys Thr Thr Pro Thr Thr Leu Asn Tyr Arg180 185 190Lys Lys Glu Phe Ser Arg Ile Asn Glu Asp Asn Ala Lys Asn Leu Gln195 200 205Glu Val Leu Asn Asn Asn Thr Leu Lys Ser Lys Leu Gly Val Asp Ile210 215 220Glu Ser Leu Glu Glu Asp Asn Thr Gln Ile Lys Val Asn Phe Thr Asp225 230 235 240Asn Thr Ser Glu Ser Phe Asp Arg Leu Leu Tyr Ala Ile Gly Gly Ser245 250 255Thr Pro Leu Glu Phe Phe Lys Arg Cys Ser Leu Glu Leu Asp Pro Ser260 265 270Thr Asn Ile Pro Val Val Lys Glu Asn Leu Glu Ser Asn Asn Ile Pro275 280 285Asn Leu Phe Ile Val Gly Asp Ile Leu Phe Lys Ser Gly Ala Ser Ile290 295 300Ala Thr Ala Leu Asn His Gly Tyr Asp Val Ala Ile Glu Ile Ala Lys305 310 315 320Arg Leu His Ser210250211128212PRT213產酸克雷伯氏菌400250Met Gly Thr Ala Lys His Ser Lys Leu Leu Ile Leu Gly Ser Gly Pro1 5 10 15Ala Gly Tyr Thr Ala Ala Val Tyr Ala Ala Arg Ala Asn Leu Gln Pro20 25 30Val Leu Ile Thr Gly Met Glu Lys Gly Gly Gln Leu Thr Thr Thr Thr35 40 45Glu Val Glu Asn Trp Pro Gly Asp Pro Asn Asp Leu Thr Gly Pro Leu50 55 60Leu Met Glu Arg Met His Glu His Ala Thr Lys Phe Glu Thr Glu Ile65 70 75 80Ile Phe Asp His Ile Asn Ser Val Asp Leu Gln Asn Arg Pro Phe Arg85 90 95Leu Val Gly Asp Ser Gly Glu Tyr Thr Cys Asp Ala Pro Asp Tyr Arg100 105 110Tyr Arg Arg Ile Ser Ala Leu Ser Gly Ser Ala Ile Gly Arg Arg Val115 120 12521025121179212PRT213乳酸乳球菌400251Met Gln Glu Leu Asp Leu Ile Ile Val Gly Ala Gly Pro Val Gly Leu1 5 10 15Tyr Ala Ala Phe Tyr Ala Gly Met Arg Gly Leu Ser Val Ala Ile Ile20 25 30Glu Ser Ala Gln Val Pro Gly Gly Gln Pro Gln Asn Leu Tyr Pro Glu35 40 45Lys Leu Ile Tyr Asp Ile Ala Gly Leu Pro Ala Val Thr Gly Ala Asp50 55 60Leu Thr Lys Asn Leu Leu Glu Gln Leu Ala Gln Ile Ser His Arg65 70 75210252211321212PRT213乳酸乳球菌400252Met Gln Glu Leu Asp Leu Ile Ile Val Gly Ala Gly Pro Val Gly Leu1 5 10 15Tyr Ala Ala Phe Tyr Ala Gly Met Arg Gly Leu Ser Val Ala Ile Ile20 25 30Glu Ser Ala Gln Val Pro Gly Gly Gln Pro Gln Asn Leu Tyr Pro Glu
35 40 45Lys Leu Ile Tyr Asp Ile Ala Gly Leu Pro Ala Val Thr Gly Ala Asp50 55 60Leu Thr Lys Asn Leu Leu Glu Gln Leu Ala Gln Ile Ser His Arg Leu65 70 75 80Phe Leu Gly Glu Ser Val Gln Lys Ile Glu Lys Glu Glu Gly Ile Phe85 90 95Ser Val Thr Thr Asp Lys Ser Thr Arg Arg Ala Lys Gly Val Leu Leu100 105 110Thr Thr Gly Ala Gly Leu Leu Lys Pro Arg Lys Leu Gly Ile Asp Asn115 120 125Glu Glu Thr Leu Ala Asn Glu Gly Lys Ile Ser Tyr Phe Ile Thr Ser130 135 140Leu Lys Glu Phe Glu Gly Lys Asn Val Ala Val Phe Gly Gly Gly Asp145 150 155 160Ser Ala Leu Asp Trp Ser Leu Met Leu Glu Lys Val Ala Lys Asn Val165 170 175His Leu Val His Arg Arg Thr Ala Phe Arg Gly His Glu Ile Thr Val180 185 190Asp Arg Val Met Asn Ser Asn Val Gln Val His Thr Pro Tyr Thr Phe195 200 205Ser Asn Leu Ile Glu Asn Glu Leu Glu Leu Lys Lys Ile Lys Ser Glu210 215 220Glu Ser Leu Asn Phe Ser Ile Asp Lys Ile Leu Val Asn Tyr Gly Phe225 230 235 240Leu Thr Asn Gln Val Thr Leu Ala Glu Asn Leu Glu Val Ser Arg Asn245 250 255Gly Arg Val Lys Ala Asp Ser Met Met Gln Ser Asn Ile Glu Gly Leu260 265 270Tyr Val Ala Gly Asp Ala Ser Asp Tyr Pro Gly Lys Met Pro Leu Met275 280 285Ser Val Gly Phe Gly Glu Ala Val His Ala Ile Asn Ala Met Thr Lys290 295 300Lys Leu Glu Phe Asp His Pro Leu Arg Gly Gly His Ser Ser Ser Ile305 310 315 320Phe210253211308212PRT213乳酸乳球菌400253Met Thr Glu Lys Lys Tyr Asp Val Val Ile Ile Gly Ser Gly Pro Ala1 5 10 15Gly Met Thr Ala Ala Met Tyr Thr Ala Arg Ser Glu Met Lys Thr Leu20 25 30Leu Leu Glu Arg Gly Val Pro Gly Gly Gln Met Asn Asn Thr Ala Glu35 40 45Ile Glu Asn Tyr Pro Gly Tyr Glu Thr Ile Met Gly Pro Glu Leu Ser50 55 60Met Lys Met Ala Glu Pro Leu Glu Gly Leu Gly Val Glu Asn Ala Tyr65 70 75 80Gly Phe Val Thr Ala Ile Glu Asp His Gly Asp Tyr Lys Lys Ile Ile85 90 95Thr Glu Asp Asp Glu Phe Val Thr Lys Ser Ile Ile Ile Ala Thr Gly100 105 110Ala Asn His Arg Lys Leu Glu Ile Pro Gly Glu Glu Glu Tyr Gly Ala115 120 125Arg Gly Val Ser Tyr Cys Ala Val Cys Asp Gly Ala Phe Phe Arg Asn130 135 140Gln Glu Ile Leu Val Ile Gly Gly Gly Asp Ser Ala Val Glu Glu Ala145 150 155 160Leu Tyr Leu Thr Arg Phe Gly Gln Ser Val Thr Ile Met His Arg Arg165 170 175Asp Lys Leu Arg Ala Gln Glu Ile Ile Gln Gln Arg Ala Phe Lys Glu180 185 190Glu Lys Ile Asn Phe Ile Trp Asp Ser Val Pro Met Glu Ile Lys Gly195 200 205Asp Asp Lys Lys Val Gln Ser Val Val Tyr Lys Asn Val Lys Thr Gly210 215 220Glu Val Thr Glu Lys Ala Phe Gly Gly Ile Phe Ile Tyr Val Gly Leu225 230 235 240Asp Pro Val Ala Glu Phe Ala Gly Asn Leu Gly Ile Thr Asp Glu Ala245 250 255Gly Trp Ile Ile Thr Asp Asp His Met Arg Thr Ser Leu Pro Gly Ile260 265 270Phe Ala Val Gly Asp Val Arg Gln Lys Asp Phe Arg Gln Ile Thr Thr275 280 285Ala Ile Gly Asp Gly Ala Gln Ala Ala Gln Glu Ala Tyr Lys Phe Val290 295 300Ala Glu Leu Asp30521025421144212PRT213乳酸乳球菌400254Met Gln Glu Leu Asp Leu Ile Ile Val Gly Ala Gly Pro Val Gly Leu1 5 10 15Tyr Ala Ala Phe Tyr Ala Gly Met Arg Gly Leu Ser Val Ala Ile Ile20 25 30Glu Ser Ala Gln Val Pro Gly Gly Gln Pro Gln Asn35 40210255211339212PRT213單核細胞增生利斯特氏菌400255Glu Phe Tyr Ser Tyr Lys Lys Glu Ile Asn Arg Tyr Leu Ala Glu Glu1 5 10 15Asp Ser Ala Ser Ala Cys Asp Ile Leu Arg Lys Val Ile Asp Glu Lys20 25 30Pro Asn Phe Trp Pro Ala Tyr Asn Gln Leu Ala Ser Leu Tyr Phe Glu35 40 45Gln Leu Lys Glu Glu Glu Gly Val Arg Val Leu Ser Asp Leu Leu Ser50 55 60Arg Asn Pro Gly Asn Leu Leu Gly Ile Cys Asp Leu Phe Ile Tyr His65 70 75 80Phe Tyr Lys Gly Asn Arg Lys Glu Ala Asp Glu Leu Tyr Leu Glu Leu85 90 95Arg Asp Val Leu Pro Val Leu Ala His His Lys Glu Lys Leu Gly Leu100 105 110Ile His Ala Met Met Gly Glu Tyr Glu Glu Ala Asp Asp Leu Leu Glu115 120 125Gln Val Ala Asp Leu Glu Val Thr Glu Arg Ser Lys Tyr Tyr Tyr Phe130 135 140Arg Ala Lys Ser Ser Tyr Tyr Leu Gly Asp Val Glu Gly Ala Lys Met145 150 155 160Phe Trp His Ser Phe Leu Glu Cys Asp Leu Tyr Glu Asp Val Arg Phe165 170 175Pro Trp Glu Gln Glu Pro Asp Leu Thr Asn Asp Thr Arg Leu Val Leu180 185 190Glu Met Leu Gln Glu Glu Asp Asp Leu Thr His Met Leu Gly Val Tyr195 200 205Ala Leu Thr Ile Ser Gly Asn Arg Pro Glu Leu Val Leu Phe His Pro
210 215 220Leu Leu Asp Met Ser Asp Trp Ser Tyr Met Glu His Leu Met Phe Thr225 230 235 240Asn Phe Asp Tyr Phe Pro Asp Gly Ala Ile Glu Gln Asn Gly Tyr Leu245 250 255Ile Ala Lys Ala Met Ile Ile Leu Lys Glu Asn Gly Ile Leu Leu Asn260 265 270Glu Glu Tyr Met Ala Leu Tyr Lys Gln Met Phe Ser Leu Val Leu Ile275 280 285Asp Ala Gly Lys Asp Leu Ile Leu Gly Arg Tyr Thr Ile Glu Thr Val290 295 300Ala Ser Ala Ile Ala Lys Leu Phe Leu Pro His Leu Lys Leu Gln Leu305 310 315 320Val Glu Glu Phe Glu Cys Ser Lys Cys Ala Arg Asp Ile Glu Arg Val325 330 335Leu Ser Arg210256211303212PRT213Methanothermobacter thermautotrophicus400256Met Met Thr Asp Tyr Asp Met Ile Val Ile Gly Ala Gly Pro Ala Gly1 5 10 15Leu Thr Ala Gly Ile Tyr Gly Gly Arg Gln Gly Ser Ser Val Leu Met20 25 30Leu Asp Lys Gly Pro Ala Gly Gly Leu Gly Leu Glu Val Pro Met Met35 40 45Glu Asn Tyr Pro Gly Phe Glu Met Ile Ala Gly Met Ser Leu Val Thr50 55 60Lys Met Lys Lys Gln Ala Thr Ala Val Ala Glu Leu Arg Glu Met Glu65 70 75 80Glu Val Lys Glu Ile Glu Lys Gly Asp Val Phe Thr Val Lys Thr Ser85 90 95Arg Asp Thr Tyr Thr Ala Ser Ala Ile Ile Phe Ala Thr Gly Ser Lys100 105 110His Arg Gln reu Gly Val Pro Gly Glu Asn Asp Leu Leu Gly Arg Gly115 120 125Val Cys Tyr Cys Ala Thr Cys Asp Gly Pro Leu Tyr Lys Gly Arg Lys130 135 140Val Leu Met Val Gly Gly Gly Asn Ser Ala Ala Gln Glu Ala Val Phe145 150 155 160Leu Lys Asn Ile Gly Cys Asp Val Ser Ile Val His Arg Arg Asp Glu165 170 175Leu Arg Ala Asp Lys Tyr Leu Gln Asp Lys Leu Arg Glu Met Glu Ile180 185 190Pro Val Ile Trp Asn Ser Val Val Lys Glu Ile Gly Gly Asp Glu Arg195 200 205Val Glu Glu Val Ile Ile His Asn Arg Val Thr Gly Arg Asp Glu Thr210 215 220Leu Lys Val Asp Gly Val Phe Ile Ala Ile Gly Glu Glu Pro Leu Asn225 230 235 240Gln Leu Ala Val Asp Leu Gly Val Glu Val Asp Lys Gly Gly Tyr Ile245 250 255Ile Thr Asp Lys Phe Gln Arg Thr Asn Val Pro Leu Val Tyr Ala Ala260 265 270Gly Asp Ile Thr Gly Gly Leu Asn Gln Trp Val Thr Ala Cys Ala Glu275 280 285Gly Ala Ile Ala Ala Thr Tyr Ala Tyr Arg Glu Ile Gln Ser Tyr290 295 300210257211179212PRT213枯草芽孢桿菌400257Met Val Ile Ser Gly Gly Gly Asp Thr Ala Val Asp Trp Ala Asn Glu1 5 10 15Leu Glu Pro Ile Ala Ala Ser Val Thr Val Val His Arg Arg Glu Glu20 25 30Phe Gly Gly Met Glu Ser Ser Val Thr Lys Met Lys Gln Ser Ser Val35 40 45Arg Val Leu Thr Pro Tyr Arg Leu Glu Gln Leu Asn Gly Asp Glu Glu50 55 60Gly Ile Lys Ser Val Thr Val Cys His Thr Glu Ser Gly Gln Arg Lys65 70 75 80Asp Ile Glu Ile Asp Glu Leu Ile Ile Asn His Gly Phe Lys Ile Asp85 90 95Leu Gly Pro Met Met Glu Trp Gly Leu Glu Ile Glu Glu Gly Arg Val100 105 110Lys Ala Asp Arg His Met Arg Thr Asn Leu Pro Gly Val Phe Val Ala115 120 125Gly Asp Ala Ala Phe Tyr Glu Ser Lys Leu Arg Leu Ile Ala Gly Gly130 135 140Phe Thr Glu Gly Pro Thr Ala Val Asn Ser Ala Lys Ala Tyr Leu Asp145 150 155 160Pro Lys Ala Glu Asn Met Ala Met Tyr Ser Thr His His Lys Lys Leu165 170 175Val His Lys210258211307212PRT213肺枝原體400258Met Ser Gln Asn Lys Ile Tyr Asp Val Ala Ile Ile Gly Ala Gly Pro1 5 10 15Gly Ala Leu Thr Ala Ala Ile Tyr Thr Ser Arg Gly Asn Leu Asp Thr20 25 30Val Phe Ile Asp Asn Ala Ala Pro Gly Gly Lys Leu Ile Tyr Ala Ser35 40 45Lys Ile Glu Asn Trp Pro Gly Asp Thr Ile Val Lys Gly Thr Asp Leu50 55 60Ala Ile Arg Phe Phe Glu His Ala Gln Ala Phe Gly Ala Lys Tyr Glu65 70 75 80Tyr Gly Lys Val Val Asp Leu Ile Asn Ile Lys Asp Asp Leu Lys Glu85 90 95Leu Val Leu Glu Asp Gly Lys Lys Ile Gln Ala Lys Ser Val Ile Ile100 105 110Ala Ser Gly Met Val Ser Arg Lys Pro Arg Glu Ile Leu Asn Tyr Asp115 120 125Glu Phe Glu Asn Arg Gly Val Ser Tyr Cys Val Ile Cys Asp Gly Pro130 135 140Met Tyr Gly His Asn Pro Ala Ile Ile Ile Gly Gly Gly Asn Ser Ala145 150 155 160Val Glu Glu Gly Thr Phe Leu Ser Ser Ile Ala Ser Lys Val Tyr Val165 170 175Ile Val Arg Asp Ser Asp Phe Ile Ala Glu Lys Ala Leu Val Asn Asp180 185 190Leu Lys Ser Arg Lys Asn Ile Glu Val Leu Phe Asn Ala Ser Val Lys195 200 205Glu Leu His Gly Lys Asp Ala Leu Glu Tyr Ala Ile Val Asn His Asn210 215 220Gly Lys Glu Val Lys Leu Glu Val Ala Ser Leu Phe Pro Tyr Ile Gly225 230 235 240Phe Leu Pro Ser Ala Glu Tyr Ala Lys Asn Ala Gly Val Leu Glu Pro
245 250255Asn Gly Phe Ile Lys Thr Asp Glu Phe Met Glu Thr Lys Val Pro Gly260 265 270Ile Tyr Ala Ile Gly Asp Ile Arg Ile Lys Asp Ile Arg Gln Ile Leu275 280 285Thr Ala Thr Ser Asp Gly Thr Ile Ala Gly Lys Ile Leu Thr Asn Arg290 295 300Ile Lys Lys305210259211316212PRT213腦膜炎奈瑟氏球菌400259Met Ser Gln His Arg Lys Leu Ile Ile Leu Gly Ser Gly Pro Ala Gly1 5 10 15Tyr Thr Ala Ala Val Tyr Ala Ala Arg Ala Asn Leu Asn Pro Val Ile20 25 30Ile Thr Gly Ile Ala Gln Gly Gly Gln Leu Met Thr Thr Thr Glu Val35 40 45Asp Asn Trp Pro Ala Asp Ala Asp Gly Val Gln Gly Thr Glu Leu Met50 55 60Ala Arg Phe Leu Ala His Ala Glu Arg Phe Gly Thr Glu Ile Ile Phe65 70 75 80Asp Gln Ile Asn Ala Val Asp Leu Gln Lys Arg Pro Phe Thr Leu Lys85 90 95Gly Asp Met Gly Glu Tyr Thr Cys Asp Ala Leu Ile Val Ala Thr Gly100 105 110Ala Ser Ala Lys Tyr Leu Gly Leu Pro Ser Glu Glu Ala Phe Ala Gly115 120 125Lys Gly Val Ser Ala Cys Ala Thr Cys Asp Gly Phe Phe Tyr Lys Asn130 135 140Gln Asp Val Ala Val Val Gly Gly Gly Asn Thr Ala Val Glu Glu Ala145 150 155 160Leu Tyr Leu Ala Asn Ile Ala Lys Thr Val Thr Leu Ile His Arg Arg165 170 175Ser Glu Phe Arg Ala Glu Lys Ile Met Ile Asp Lys Leu Met Lys Arg180 185 190Val Glu Glu Gly Lys Ile Ile Leu Lys Leu Glu Ser Asn Leu Gln Glu195 200 205Val Leu Gly Asp Asp Arg Gly Val Asn Gly Ala Leu Leu Lys Asn Asn210 215 220Asp Gly Ser Glu Gln Gln Ile Ala Val Ser Gly Ile Phe Ile Ala Ile225 230 235 240Gly His Lys Pro Asn Thr Asp Ile Phe Lys Gly Gln Leu Glu Met Asp245 250 255Glu Ala Gly Tyr Leu Lys Thr Lys Gly Gly Thr Ala Asp Asn Val Gly260 265 270Ala Thr Asn Ile Glu Gly Val Trp Ala Ala Gly Asp Val Lys Asp His275 280 285Thr Tyr Arg Gln Ala Ile Thr Ser Ala Ala Ser Gly Cys Gln Ala Ala290 295 300Leu Asp Ala Glu Arg Trp Leu Gly Ser Gln Asn Ile305 310 315210260211316212PRT213腦膜炎奈瑟氏球菌400260Met Ser Gln His Arg Lys Leu Ile Ile Leu Gly Ser Gly Pro Ala Gly1 5 10 15Tyr Thr Ala Ala Val Tyr Ala Ala Arg Ala Asn Leu Asn Pro Val Ile20 25 30Ile Thr Gly Ile Ala Gln Gly Gly Gln Leu Met Thr Thr Thr Glu Val35 40 45Asp Asn Trp Pro Ala Asp Ala Asp Gly Val Gln Gly Pro Glu Leu Met50 55 60Ala Arg Phe Leu Ala His Ala Glu Arg Phe Gly Thr Glu Ile Ile Phe65 70 75 80Asp Gln Ile Asn Ala Val Asp Leu Gln Lys Arg Pro Phe Thr Leu Lys85 90 95Gly Asp Met Gly Glu Tyr Thr Cys Asp Ala Leu Ile Val Ala Thr Gly100 105 110Ala Ser Ala Lys Tyr Leu Gly Leu Pro Ser Glu Glu Ala Phe Ala Gly115 120 125Lys Gly Val Ser Ala Cys Ala Thr Cys Asp Gly Phe Phe Tyr Lys Asn130 135 140Gln Asp Val Ala Val Val Gly Gly Gly Asn Thr Ala Val Glu Glu Ala145 150 155 160Leu Tyr Leu Ala Asn Ile Ala Lys Thr Val Thr Leu Ile His Arg Arg165 170 175Ser Glu Phe Arg Ala Glu Lys Ile Met Ile Asp Lys Leu Met Lys Arg180 185 190Val Glu Glu Gly Lys Ile Ile Leu Lys Leu Glu Ser Asn Leu Gln Glu195 200 205Val Leu Gly Asp Asp Arg Gly Val Asn Gly Ala Leu Leu Lys Asn Asn210 215 220Asp Gly Ser Glu Gln Gln Ile Ala Val Ser Gly Ile Phe Ile Ala Ile225 230 235 240Gly His Lys Pro Asn Thr Asp Ile Phe Lys Gly Gln Leu Glu Met Asp245 250 255Glu Ala Gly Tyr Leu Lys Thr Lys Gly Gly Thr Ala Asp Asn Val Gly260 265 270Ala Thr Asn Ile Glu Gly Val Trp Ala Ala Gly Asp Val Lys Asp His275 280 285Thr Tyr Arg Gln Ala Ile Thr Ser Ala Ala Ser Gly Cys Gln Ala Ala290 295 300Leu Asp Ala Glu Arg Trp Leu Gly Ser Gln Asn Ile305 310 315210261211316212PRT213銅綠假單胞菌400261Met Ser Glu Val Lys His Ser Arg Leu Ile Ile Leu Gly Ser Gly Pro1 5 10 15Ala Gly Tyr Thr Ala Ala Val Tyr Ala Ala Arg Ala Asn Leu Lys Pro20 25 30Val Val Ile Thr Gly Ile Gln Pro Gly Gly Gln Leu Thr Thr Thr Thr35 40 45Glu Val Asp Asn Trp Pro Gly Asp Val Glu Gly Leu Thr Gly Pro Ala50 55 60Leu Met Thr Arg Met Gln Gln His Ala Glu Arg Phe Asp Thr Glu Ile65 70 75 80Val Tyr Asp His Ile His Thr Ala Glu Leu Gln Glu Arg Pro Phe Thr85 90 95Leu Lys Gly Asp Ser Gly Thr Tyr Thr Cys Asp Ala Leu Ile Ile Ala100 105 110Thr Gly Ala Ser Ala Gln Tyr Leu Gly Met Ser Ser Glu Glu Ala Phe115 120 125Met Gly Lys Gly Val Ser Ala Cys Ala Thr Cys Asp Gly Phe Phe Tyr130 135 140Arg Asn Gln Val Val Cys Val Val Gly Gly Gly Asn Thr Ala Val Glu145 150 155 160Glu Ala Leu Tyr Leu Ala Asn Ile Ala Lys Glu Val His Leu Ile His
165 170 175Arg Arg Asp Lys Leu Arg Ser Glu Lys Ile Leu Gln Asp Lys Leu Phe180 185 190Asp Lys Ala Glu Asn Gly Asn Val His Leu His Trp Asn Thr Thr Leu195 200 205Asp Glu Val Leu Gly Asp Ala Ser Gly Val Thr Gly Val Arg Leu Lys210 215 220Ser Thr Ile Asp Gly Ser Thr Ser Glu Leu Ser Leu Ala Gly Val Phe225 230 235 240Ile Ala Ile Gly His Lys Pro Asn Thr Asp Leu Phe Gln Gly Gln Leu245 250 255Glu Met Arg Asp Gly Tyr Leu Arg Ile His Gly Gly Ser Glu Gly Asn260 265 270Ala Thr Gln Thr Ser Ile Glu Gly Val Phe Ala Ala Gly Asp Val Ala275 280 285Asp His Val Tyr Arg Gln Ala Ile Thr Ser Ala Gly Ala Gly Cys Met290 295 300Ala Ala Leu Asp Ala Glu Lys Tyr Leu Asp Asp His305 310 315210262211316212PRT213銅綠假單胞菌400262Met Pro Asp Thr Leu Arg His Ala Arg Val Ile Ile Leu Gly Ser Gly1 5 10 15Pro Ala Gly Tyr Ser Ala Ala Val Tyr Ala Ala Arg Ala Asn Leu Lys20 25 30Pro Leu Leu Ile Thr Gly Met Gln Ala Gly Gly Gln Leu Thr Thr Thr35 40 45Thr Glu Val Asp Asn Trp Pro Gly Asp Pro His Gly Leu Thr Gly Pro50 55 60Ala Leu Met Gln Arg Met Gln Glu His Ala Glu Arg Phe Glu Thr Glu65 70 75 80Ile Val Phe Asp His Ile His Ala Val Asp Leu Ala Gly Lys Pro Phe85 90 95Thr Leu Arg Gly Asp Asn Gly Thr Tyr Thr Cys Asp Ala Leu Ile Val100 105 110Ala Thr Gly Ala Ser Ala Arg Tyr Leu Gly Leu Pro Ser Glu Gln Ala115 120 125Phe Met Gly Lys Gly Val Ser Ala Cys Ala Thr Cys Asp Gly Phe Phe130 135 140Tyr Arg Asn Arg Glu Val Ala Val Ile Gly Gly Gly Asn Thr Ala Val145 150 155 160Glu Glu Ala Leu Tyr Leu Ala Asn Ile Ala Ser Arg Val Thr Leu Val165 170 175His Arg Arg Glu Thr Phe Arg Ala Glu Lys Ile Leu Gln Asp Lys Leu180 185 190Gln Ala Arg Val Ala Glu Gly Lys Ile Val Leu Lys Leu Asn Ala Glu195 200 205Val Asp Glu Val Leu Gly Asp Thr Met Gly Val Thr Gly Val Arg Leu210 215 220Lys Thr Arg Asp Gly Gly Ser Glu Glu Ile Ala Val Asp Gly Met Phe225 230 235 240Val Ala Ile Gly His Thr Pro Asn Thr Ser Leu Phe Glu Gly Gln Leu245 250 255Ala Leu Lys Asp Gly Tyr Leu Val Val Asn Gly Gly Arg Glu Gly Asn260 265 270Ala Thr Ala Thr Asn Val Pro Gly Val Phe Ala Ala Gly Asp Val Ala275 280 285Asp His Val Tyr Arg Gln Ala Ile Thr Ser Ala Gly Ala Gly Cys Met290 295 300Ala Ala Leu Asp Val Glu Arg Tyr Leu Asp Ser Leu305 310 315210263211345212PRT213Pyrococcus abyssi400263Met Leu Leu Asn Ile His Gln Glu Ser Tyr Val Glu Val Val Lys Met1 5 10 15Phe Ser Leu Gly Gly Leu Gly Lys Ser Arg Val Asp Glu Ser Lys Val20 25 30Trp Asp Val Ile Ile Ile Gly Ala Gly Pro Ala Gly Tyr Thr Ala Ala35 40 45Ile Tyr Ala Ala Arg Phe Gly Leu Asp Thr Ile Ile Ile Thr Lys Asp50 55 60Leu Gly Gly Asn Met Ala Ile Thr Asp Leu Ile Glu Asn Tyr Pro Gly65 70 75 80Phe Pro Glu Gly Ile Ser Gly Ser Glu Leu Ala Lys Arg Met Tyr Glu85 90 95His Val Lys Lys Tyr Gly Val Asp Val Ile Phe Asp Glu Val Val Arg100 105 110Ile Asp Pro Ala Glu Cys Ala Tyr Tyr Glu Gly Pro Cys Gln Phe Glu115 120 125Val Lys Thr Ala Asn Gly Lys Glu Tyr Lys Gly Lys Thr Ile Ile Ile130 135 140Ala Val Gly Ala Glu Pro Arg Lys Leu His Val Pro Gly Glu Lys Glu145 150 155 160Phe Thr Gly Arg Gly Val Ser Tyr Cys Ala Thr Cys Asp Gly Pro Leu165 170 175Phe Val Gly Lys Glu Val Ile Val Val Gly Gly Gly Asn Thr Ala Leu180 185 190Gln Glu Ala Leu Tyr Leu His Ser Ile Gly Val Lys Val Thr Leu Val195 200 205His Arg Arg Asp Lys Phe Arg Ala Asp Lys Ile Leu Gln Asp Arg Leu210 215220Lys Gln Ala Gly Ile Pro Thr Ile Leu Asn Thr Val Val Thr Glu Ile225 230 235 240Arg Gly Thr Asn Lys Val Glu Ser Val Val Leu Lys Asn Val Lys Thr245 250 255Gly Glu Thr Phe Glu Lys Lys Val Asp Gly Val Phe Ile Phe Ile Gly260 265 270Tyr Glu Pro Lys Thr Asp Phe Val Lys His Leu Gly Ile Thr Asp Glu275 280 285Tyr Gly Tyr Ile Lys Val Asp Met Tyr Met Arg Thr Lys Val Pro Gly290 295 300Ile Phe Ala Ala Gly Asp Ile Thr Asn Val Phe Lys Gln Ile Ala Val305 310 315 320Ala Val Gly Gln Gly Ala Ile Ala Ala Asn Ser Ala Lys Glu Phe Ile325 330 335Glu Ser Trp Asn Gly Lys Ser Ile Glu340 345210264211334212PRT213普魯畫斯克氏立克次氏體400264Met Tyr Asn Thr Asp Ile Val Ile Ile Gly Ser Gly Pro Val Gly Leu1 5 10 15Phe Ala Val Phe Gln Ala Gly Met Leu Gly Met Lys Cys His Val Ile20 25 30Asp Ala Gln Glu Val Ile Gly Gly Gln Cys Ile Thr Leu Tyr Pro Glu35 40 45Lys His Ile Tyr Asp Ile Pro Ala Tyr Pro Lys Ile Ala Ala Lys Glu50 55 60Leu Ile Lys Gln Leu Glu Ser Gln Ala Ala Pro Phe Asn Pro Val Tyr65 70 75 80His Leu Asn Gln Gln Ala Thr Glu Leu Asn Lys His Asp Asp Phe Phe85 90 95Glu Ile Lys Thr Ser Lys Asn Thr Leu Ile Lys Ser Lys Val Ile Ile100 105 110Ile Ala Ala Gly Ala Gly Ala Phe Gly Pro Asn Lys Pro Pro Ile Ala115 120 125Asn Ile Glu Ala Phe Glu Gly Lys Ser Ile Phe Tyr Phe Ile Asn Asp130 135140Lys Ser Lys Phe Leu Gly Lys Asn Ile Val Val Ala Gly Gly Gly Asp145 150 155 160Ser Ala Val Asp Trp Ala Ile Thr Leu Ser Glu Ile Ala Asn Lys Ile165 170 175Tyr Leu Val His Arg Arg Asp Lys Phe Thr Ala Ala Thr Glu Ser Val180 185 190Arg Gln Leu Arg His Ile Ala Glu Thr Gly Lys Ile Glu Leu Val Thr195 200 205Gly Tyr Gln Leu Asn Asn Leu Asp Gly His Asn Ser Glu Leu Arg Ser210 215 220Val Ile Val Lys Asp Leu Gln Asn Asn Ile Arg Lys Leu Asp Ala Asn225 230 235 240Ile Leu Leu Pro Phe Phe Gly Leu Lys Gln Asp Leu Gly Pro Leu Ala245250 255Asn Trp Gly Phe Asn Val Arg Leu Gln His Ile Glu Val Asp Asn Tyr260 265 270Tyr Tyr Gln Thr Asn Ile Lys Gly Ile Tyr Ala Ile Gly Asp Val Ala275 280 285His Tyr Val Gly Lys Leu Lys Leu Ile Ile Thr Gly Phe Ala Glu Ala290 295 300Ala Cys Ser Leu His His Ala Tyr Ser Arg Val Phe Asp Gly Lys Ala305 310 315 320Leu His Phe Glu Tyr Ser Thr Asn Lys Tyr Glu Gln Lys Gln325 330210265211311212PRT213金黃色葡萄球菌400265Met Thr Glu Ile Asp Phe Asp Ile Ala Ile Ile Gly Ala Gly Pro Ala1 5 10 15Gly Met Thr Ala Ala Val Tyr Ala Ser Arg Ala Asn Leu Lys Thr Val20 25 30Met Ile Glu Arg Gly Ile Pro Gly Gly Gln Met Ala Asn Thr Glu Glu35 40 45Val Glu Asn Phe Pro Gly Phe Glu Met Ile Thr Gly Pro Asp Leu Ser50 55 60Thr Lys Met Phe Glu His Ala Lys Lys Phe Gly Ala Val Tyr Gln Tyr65 70 75 80Gly Asp Ile Lys Ser Val Glu Asp Lys Gly Glu Tyr Lys Val Ile Asn85 90 95Phe Gly Asn Lys Glu Leu Thr Ala Lys Ala Val Ile Ile Ala Thr Gly100 105 110Ala Gly Tyr Lys Lys Ile Gly Val Pro Gly Glu Gln Glu Leu Gly Gly115 120 125Arg Gly Val Ser Tyr Cys Ala Val Cys Asp Gly Ala Phe Phe Lys Asn130 135 140Lys Arg Leu Phe Val Ile Gly Gly Gly Asp Ser Ala Val Glu Glu Gly145 150 155 160Thr Phe Leu Thr Lys Phe Ala Asp Lys Val Thr Ile Val His Arg Arg165 170 175Asp Glu Leu Arg Ala Gln Arg Ile Leu Gln Asp Arg Ala Phe Lys Asn180 185 190Asp Lys Ile Asp Phe Ile Trp Ser His Thr Leu Lys Ser Ile Asn Glu
195 200 205Lys Asp Gly Lys Val Gly Ser Val Thr Leu Thr Ser Thr Lys Asp Gly210 215 220Ser Glu Glu Thr His Glu Ala Asp Gly Val Phe Ile Tyr Ile Gly Met225 230 235 240Lys Pro Leu Thr Ala Pro Phe Lys Asp Leu Gly Ile Thr Asn Asp Val245 250 255Gly Tyr Ile Val Thr Lys Asp Asp Met Thr Thr Ser Val Pro Gly Ile260 265 270Phe Ala Ala Gly Asp Val Arg Asp Lys Gly Leu Arg Gln Ile Val Thr275 280 285Ala Thr Gly Asp Gly Ser Ile Ala Ala Gln Ser Thr Ser Gly Tyr Ile290 295 300Glu His Leu Asn Asp Gln Ala305 310210266211326212PRT213天藍色葡萄球菌400266Met Ser Thr Ala Lys Asp Val Arg Asp Val Ile Val Ile Gly Ser Gly1 5 10 15Pro Ala Gly Tyr Thr Ala Ala Leu Tyr Thr Ala Arg Ala Ser Leu Asn20 25 30Pro Leu Val Phe Gly Gly Ala Ile Phe Val Gly Gly Ser Leu Thr Thr35 40 45Thr Thr Glu Val Glu Asn Phe Pro Gly Phe Pro Asp Gly Val Gln Gly50 55 60Pro Glu Leu Met Glu Asn Met Arg Ala Gln Ala Glu Arg Phe Gly Ala65 70 75 80Glu Met Val Asp Asp Asp Ile Val Ala Val Asp Leu Thr Gly Asp Val85 90 95Lys Thr Val Thr Asp Thr Ala Gly Thr Val His Arg Ala Arg Thr Val100 105 110Ile Val Ala Thr Gly Ser Gly Tyr Arg Lys Leu Gly Val Pro Lys Glu115 120 125Asp Glu Leu Ser Gly Arg Gly Val Ser Trp Cys Ala Thr Cys Asp Gly130 135 140Phe Phe Phe Arg Asp Arg Asp Ile Val Val Val Gly Gly Gly Asp Thr145 150 155 160Ala Met Glu Glu Ala Thr Phe Leu Thr Arg Phe Ala Arg Ser Val Thr165 170 175Val Val His Arg Arg Ser Ala Leu Arg Ala Ser Gln Val Met Gln Asn180 185 190Arg Ala Phe Ser Glu Asp Lys Ile Ser Leu Ala Phe Asp Ser Glu Val195 200 205Ala Thr Leu His Glu Glu Asn Gly Met Leu Ser Gly Met Thr Leu Arg210 215 220Asp Thr Leu Thr Gly Glu Thr Arg Glu Leu Ala Thr Thr Gly Leu Phe225 230 235 240Ile Ala Ile Gly His Asp Pro Arg Thr Glu Leu Phe Lys Gly Gln Leu245 250 255His Leu Asp Ser Glu Gly Tyr Leu Met Val Glu Ser Pro Ser Thr Arg260 265 270Thr Asn Val Pro Gly Val Phe Gly Ala Gly Asp Val Val Asp His Thr275 280 285Tyr Arg Gln Ala Ile Thr Ala Ala Ser Ser Gly Cys Ala Ala Ala Leu290 295 300Asp Ala Glu Arg Tyr Leu Ala Ala Arg Ser Asp Thr Ser Val Ser Ala305 310 315 320Glu Val Val Ala Val Ala325210267211558212PRT213天藍色鏈黴菌400267Met Ala Gln Ala Asp Gly Glu Thr Arg Thr Val Ile Met Thr Val Asp1 5 10 15Asp Asp Pro Gly Val Ser Arg Ala Val Ala Arg Asp Leu Arg Arg Arg20 25 30Tyr Gly Ala Thr Tyr Arg Ile Val Arg Ala Glu Ser Gly Glu Ser Ala35 40 45Leu Asp Ala Leu Arg Glu Leu Lys Leu Arg Gly Asp Leu Val Ala Val50 55 60Ile Leu Ala Asp Tyr Arg Met Pro Gln Met Asn Gly Ile Glu Phe Leu65 70 75 80Glu Gln Ala Leu Asp Val Tyr Pro Gly Ala Arg Arg Val Leu Leu Thr85 90 95Ala Tyr Ala Asp Thr Asn Ala Ala Ile Asp Ala Ile Asn Val Val Asp100 105 110Leu Asp His Tyr Leu Leu Lys Pro Trp Asp Pro Pro Glu Glu Lys Leu115 120 125Tyr Pro Val Leu Asp Asp Leu Leu Gln Ala Trp Arg Ala Gly Asp His130 135 140Arg Pro Val Pro Ser Thr Lys Val Val Gly His Arg Trp Ser Ala Arg145 150 155 160Ser Ser Glu Val Arg Glu Phe Leu Ala Arg Asn Gln Val Pro Tyr Arg165 170 175Trp Tyr Ser Ser Asp Glu Pro Glu Gly Arg Arg Leu Leu Ser Ala Ala180 185 190Gly Gln Asp Gly Gln Arg Leu Pro Val Val Ile Thr Pro Asp Gly Thr195 200 205Pro Leu Val Glu Pro Glu Ala Pro Glu Leu Ala Ala Arg Val Gly Leu210 215 220Ala Thr Thr Pro Thr Ser Asp Phe Tyr Asp Leu Val Val Ile Gly Gly225 230 235 240Gly Pro Ala Gly Leu Gly Ala Ala Val Tyr Gly Ala Ser Glu Gly Leu245 250 255Arg Thr Val Leu Val Glu Arg Ser Ala Thr Gly Gly Gln Ala Gly Gln260 265 270Ser Ser Arg Ile Glu Asn Tyr Leu Gly Phe Pro Asp Gly Val Ser Gly275 280 285Gly Gln Leu Thr Glu Arg Ala Arg Arg Gln Ala Ala Arg Phe Gly Ala290 295 300Glu Ile Leu Thr Ala Arg Glu Val Thr Gly Leu Glu Ala Asn Gly Ala305 310 315 320Ala Arg Val Val Arg Phe Ser Asp Gly Ser Ala Ile Ala Ala His Ser325 330 335Val Ile Leu Ala Thr Gly Val Ser Tyr Arg Gln Leu Thr Ala Pro Gly340 345 350Thr Glu Asp Leu Ala Gly Cys Gly Val Phe Tyr Gly Ser Ala Leu Thr355 360 365Glu Ala Ala Ser Cys Gln Gly His Asp Val Tyr Ile Val Gly Gly Ala370 375 380Asn Ser Ala Gly Gln Ala Ala Met Tyr Leu Ala Arg Gly Ala Lys Ser385 390 395 400Val Thr Leu Leu Val Arg Gly Gly Ser Leu Glu Ala Ser Met Ser Tyr405 410 415Tyr Leu Ile Gln Gln Ile Glu Glu Thr Pro Asn Ile Arg Val Arg Cys420 425 430Gly Thr Leu Val Glu Gly Ala His Gly Asp Gly His Leu Glu Arg Leu435 440 445Thr Leu Arg Asp Ala Ala Ser Gly Ala Thr Glu Leu Val Asp Ala Gln450 455 460Trp Leu Phe Val Phe Ile Gly Ala Ala Pro Leu Thr Asp Trp Leu Asp465 470 475 480Gly Thr Val Leu Arg Asp Glu Arg Gly Phe Ile Leu Ala Gly Pro Asp
485 490 495Leu Thr Pro Asp Gly Arg Pro Pro Ala Gly Trp Glu Leu Asp Arg Pro500 505 510Pro Tyr His Leu Glu Thr Ser Val Pro Gly Val Phe Val Ala Gly Asp515 520 525Ala Arg Ala Glu Ser Ala Lys Arg Val Ala Ser Ala Val Gly Glu Gly530 535 540Ala Met Ala Val Met Leu Val His Arg Tyr Leu Glu Gln Ser545 550 555210268211303212PRT213肺炎鏈球菌400268Met Tyr Asp Thr Ile Ile Ile Gly Ala Gly Pro Ala Gly Met Thr Ala1 5 10 15Ala Leu Tyr Ala Ala Arg Ser Asn Leu Lys Val Ala Leu Ile Glu Gly20 25 30Gly Leu Pro Gly Gly Gln Met Asn Asn Thr Ser Asp Ile Glu Asn Tyr35 40 45Pro Gly Tyr Ala Asn Ile Ser Gly Pro Glu Leu Ala Glu Lys Met Phe50 55 60Glu Pro Leu Glu Asn Leu Gly Val Glu His Ile Tyr Gly Tyr Val Glu65 70 75 80Asn Val Glu Asp His Gly Asp Phe Lys Lys Val Met Thr Asp Asp Gln85 90 95Thr Tyr Glu Thr Arg Thr Val Ile Val Ala Thr Gly Ser Lys His Arg100 105 110Pro Leu Gly Val Pro Gly Glu Glu Glu Leu Asn Ser Arg Gly Val Ser115 120 125Tyr Cys Ala Val Cys Asp Gly Ala Phe Phe Arg Asp Gln Asp Leu Leu130 135 140Val Val Gly Gly Gly Asp Ser Ala Val Glu Glu Ala Leu Phe Leu Thr145 150 155 160Arg Phe Ala Lys Thr Val Thr Ile Val His Arg Arg Asp Gln Leu Arg165 170 175Ala Gln Lys Val Leu Gln Asp Arg Ala Phe Ala Asn Glu Lys Ile Ser180 185 190Phe Ile Trp Asp Ser Val Val Arg Glu Ile Lys Gly Glu Asn Arg Val195 200 205Glu Ser Val Val Phe Glu Asn Val Lys Thr Gly Gln Val Thr Glu Gln210 215 220Ala Phe Gly Gly Val Phe Ile Tyr Val Gly Leu Asp Pro Leu Ser Asp225 230 235 240Phe Val Lys Glu Leu Asn Ile Gln Asp Gln Ala Gly Trp Ile Val Thr245 250 255Asp Asn His Met Lys Thr Ala Val Asp Gly Ile Phe Ala Val Gly Asp260 265 270Val Arg Leu Lys Asp Leu Arg Gln Val Thr Thr Ala Val Gly Asp Gly275 280 285Ala Ile Ala Gly Gln Glu Ala Tyr Lys Phe Ile Thr Glu His Ser290 295 300210269211330212PRT213化膿鏈球菌400269Met Lys Asp Lys Ala Tyr Asp Ile Thr Ile Ile Gly Gly Gly Pro Ile1 5 10 15Gly Leu Phe Ala Ala Phe Tyr Ala Gly Leu Arg Gly Val Thr Val Lys20 25 30Ile Ile Glu Ser Leu Ser Glu Leu Gly Gly Gln Pro Ala Ile Leu Tyr35 40 45Pro Glu Lys Met Ile Tyr Asp Ile Pro Ala Tyr Pro Ser Leu Thr Gly50 55 60Val Glu Leu Thr Glu Asn Leu Ile Lys Gln Leu Ser Arg Phe Glu Asp65 70 75 80Arg Thr Thr Ile Cys Leu Lys Glu Glu Val Leu Thr Phe Asp Lys Val85 90 95Lys Gly Gly Phe Ser Ile Arg Thr Asn Lys Ala Glu His Phe Ser Lys100 105 110Ala Ile Ile Ile Ala Cys Gly Asn Gly Ala Phe Ala Pro Arg Thr Leu115 120 125Gly Leu Glu Ser Glu Glu Asn Phe Ala Asp His Asn Leu Phe Tyr Asn130 135 140Val His Gln Leu Asp Gln Phe Ala Gly Gln Lys Val Val Ile Cys Gly145 150 155 160Gly Gly Asp Ser Ala Val Asp Trp Ala Leu Ala Leu Glu Asp Ile Ala165 170 175Glu Ser Val Thr Val Val His Arg Arg Asp Ala Phe Arg Ala His Glu180 185 190His Ser Val Glu Leu Leu Lys Ala Ser Thr Val Asn Leu Leu Thr Pro195 200 205Tyr Val Pro Lys Ala Leu Lys Gly Ile Gly Asn Leu Ala Glu Lys Leu210 215 220Val Ile Gln Lys Val Lys Glu Asp Glu Val Leu Glu Leu Glu Leu Asp225 230 235 240Ser Leu Ile Val Ser Phe Gly Phe Ser Thr Ser Asn Lys Asn Leu Lys245 250 255Asn Trp Asn Leu Asp Tyr Lys Arg Ser Ser Ile Thr Val Ser Pro Leu260 265 270Phe Gln Thr Ser Gln Glu Gly Ile Phe Ala Ile Gly Asp Ala Ala Ala275 280 285Tyr Asn Gly Lys Val Asp Leu Ile Ala Thr Gly Phe Gly Glu Ala Pro290 295 300Thr Ala Val Asn Gln Ala Ile Asn Tyr Ile Tyr Pro Asp Arg Asp Asn305 310 315 320Arg Val Val His Ser Thr Ser Leu Ile Asp325 330210270211325212PRT213硫磺礦硫化葉菌400270Met Pro Leu Lys Thr Tyr Asp Thr Ile Ile Val Gly Ala Gly Ile Ala1 5 10 15Gly Leu Ser Ala Ala Leu Tyr Ser Ser Arg Gln Lys Leu Ser Thr Leu20 25 30Val Leu Ser Lys Asp Leu Gly Gly Gln Leu Thr Leu Thr Asp Leu Ile35 40 45Glu Asn Tyr Pro Gly Ile Glu Ser Thr Gly Gly Leu Thr Leu Ala Gln50 55 60Lys Ile Glu Lys Gln Ala Lys Lys Phe Gly Ala Glu Phe Ile Tyr Gly65 70 75 80Glu Glu Val Lys Glu Ile Ala Gln Glu Ser Asp Leu Phe Ile Ile Lys85 90 95Gly Ile Lys Gly Glu Tyr Ala Gly Arg Ala Leu Ile Leu Ala Phe Gly100 105 110Lys Thr Pro Arg Glu Ile Asn Val Pro Gly Glu Gln Glu Phe Lys Gly115 120 125Lys Gly Val Ser Tyr Cys Ala Ile Cys Asp Ala Ala Phe Phe Lys Gly130 135 140Lys Pro Ala Ala Val Ile Gly Glu Gly Glu Pro Gly Ile Glu Ala Ile145 150 155 160Glu Leu Leu Ser Asn Tyr Ala Asn Pro Ala Tyr Tyr Ile Thr Ser Ser
165 170 175Ser Tyr Leu Ala Gly Glu Glu Glu Ile Val Lys Asn Val Val Asn Lys180 185 190Pro Thr Val Lys Ile Leu Thr Ser Ser Arg Val Leu Glu Ile Arg Gly195 200 205Asn Ser Lys Val Glu Glu Leu Val Ile Lys Arg Gly Asp Glu Ile Leu210 215 220Gln Leu Lys Val Asp Gly Val Ile Ile Glu Met Gly Tyr Thr Leu Lys225 230 235 240Thr Glu Phe Leu Lys Gly Phe Val Glu Leu Asn Glu Lys Gly Glu Ile245 250 255Ile Val Asp Glu Leu Gly Arg Thr Ser Arg Glu Gly Val Phe Ala Ala260 265 270Gly Asp Val Thr Gln Thr Pro Tyr Lys Gln Ala Val Val Ala Ala Ala275 280 285Glu Gly Val Lys Ala Ala Leu Ser Ala Tyr Asn Tyr Ile Arg Ser Lys290 295 300Arg Gly Leu Pro Pro Val Thr Val Asp Trp Lys Ala Glu Lys Lys Lys305 310 315 320Val Ser Phe Arg Leu325210271211323212PRT213硫磺礦硫化葉菌400271Met Ser Leu Leu Pro Arg Thr Thr Ser Val Lys Pro Gly Glu Lys Phe1 5 10 15Asp Val Ile Ile Val Gly Leu Gly Pro Ala Ala Tyr Gly Ala Ala Leu20 25 30Tyr Ser Ala Arg Tyr Met Leu Lys Thr Leu Val Ile Gly Glu Thr Pro35 40 45Gly Gly Gln Leu Thr Glu Ala Gly Ile Val Asp Asp Tyr Leu Gly Leu50 55 60Ile Glu Ile Gln Ala Ser Asp Met Ile Lys Val Phe Asn Lys His Ile65 70 75 80Glu Lys Tyr Glu Val Pro Val Leu Leu Asp Ile Val Glu Lys Ile Glu85 90 95Asn Arg Gly Asp Glu Phe Val Val Lys Thr Lys Arg Lys Gly Glu Phe100 105 110Lys Ala Asp Ser Val Ile Leu Gly Ile Gly Val Lys Arg Arg Lys Leu115 120 125Gly Val Pro Gly Glu Gln Glu Phe Ala Gly Arg Gly Ile Ser Tyr Cys130 135 140Ser Val Cys Asp Ala Pro Leu Phe Lys Asn Arg Val Val Ala Val Ile145 150 155 160Gly Gly Gly Asp Ser Ala Leu Glu Gly Ala Glu Ile Leu Ser Ser Tyr165 170 175Ser Thr Lys Val Tyr Leu Ile His Arg Arg Asp Thr Phe Lys Ala Gln180 185 190Pro Ile Tyr Val Glu Thr Val Lys Lys Lys Pro Asn Val Glu Phe Val195 200 205Leu Asn Ser Val Val Lys Glu Ile Lys Gly Asp Lys Val Val Lys Gln210 215 220Val Val Val Glu Asn Leu Lys Thr Gly Glu Ile Lys Glu Leu Asn Val225 230 235 240Asn Gly Val Phe Ile Glu Ile Gly Phe Asp Pro Pro Thr Asp Phe Ala245 250 255Lys Ser Asn Gly Ile Glu Thr Asp Thr Asn Gly Tyr Ile Lys Val Asp260 265 270Glu Trp Met Arg Thr Ser Val Pro Gly Val Phe Ala Ala Gly Asp Cys275 280 285Thr Ser Ala Trp Leu Gly Phe Arg Gln Val Ile Thr Ala Val Ala Gln290 295 300Gly Ala Val Ala Ala Thr Ser Ala Tyr Arg Tyr Val Thr Glu Lys Lys305 310 315 320Gly Lys Lys210272211332212PRT213硫磺礦硫化葉菌400272Met Asp Glu Tyr Asp Ile Val Val Ile Gly Gly Gly Pro Val Gly Leu1 5 10 15Phe Gly Thr Phe Tyr Ala Gly Leu Arg Asp Met Lys Thr Leu Leu Ile20 25 30Asp Ala Gln Asp Glu Leu Gly Gly Gln Leu Val Ser Leu Tyr Pro Glu35 40 45Lys Ile Val Tyr Asp Val Gly Gly Leu Ala Gly Ile Gln Ala Tyr Glu50 55 60Leu Ala Gln Arg Leu Ile Glu Gln Ala Lys Met Phe Gly Pro Asp Ile65 70 75 80Lys Val Asn Glu Leu Ala Asp Met Ile Glu Lys Thr Asn Asp Asn Met85 90 95Trp Ile Val Lys Thr Asp Lys Ala Thr Tyr Lys Thr Lys Thr Ile Phe100 105 110Ile Ala Ala Gly Ile Gly Lys Ile Val Pro Ser Arg Leu Gly Ala Lys115 120 125Gly Glu Ile Glu Tyr Glu Asn Arg Gly Val Tyr Tyr Thr Val Arg Arg130 135 140Lys Lys Asp Phe Glu Gly Lys Arg Val Leu Ile Val Gly Gly Gly Asp145 150 155 160Ser Ala Val Asp Trp Ala Leu Thr Leu Ala Pro Val Ala Lys Ser Val165 170 175Thr Leu Ile His Arg Arg Asp Gln Phe Arg Ala His Glu Arg Ser Val180 185 190Lys Glu Leu Phe Arg Val Ala Asn Val Tyr Val Trp His Glu Leu Lys195 200 205Glu Val Lys Gly Asp Gly Asn Lys Val Thr Gln Ala Ile Ile Phe Asp210 215 220Asn Arg Thr Lys Glu Glu Lys Val Leu Asp Val Asp Ser Val Ile Ile225 230 235 240Ser Ile Gly Tyr Lys Gly Asp Leu Gly Asn Ile Pro Lys Trp Gly Val245 250 255Thr Met Lys Gly Arg Asp Ile Val Val Asn Gly Arg Met Glu Thr Asn260 265 270Leu Pro Gly Val Tyr Ala Gly Gly Asp Ile Val Gln Met Glu Gly Ser275 280 285Pro Lys Leu Ala Leu Ile Ala Val Gly Phe Ala His Ala Ala Ile Ala290 295 300Ile Ser Val Ala Lys Lys Tyr Val Glu Pro Asn Ala Ser Leu Phe Ala305 310 315 320Gly His Ser Ser Glu Met Asp Lys Phe Lys Pro Lys325 330210273211324212PRT213百脈根瘤菌400273Met Thr Thr Lys His Ala Pro Val Leu Ile Ile Gly Ser Gly Pro Ala1 5 10 15Gly Tyr Thr Ala Ala Val Tyr Ala Ala Arg Ala Met Leu Lys Pro Met20 25 30Leu Val Ala Gly Leu Gln Gln Gly Gly Gln Leu Met Ile Thr Thr Asp
35 40 45Val Glu Asn Tyr Pro Gly Phe Ala Asp Pro Ile Gln Gly Pro Trp Leu50 55 60Met Glu Gln Met Met Lys Gln Ala Glu His Val Gly Thr Asp Ile Ile65 70 75 80Asn Asp Ile Ile Thr Glu Val Asp Leu Asn Val Arg Pro Phe Arg Ala85 90 95Lys Gly Asp Ser Gly Thr Thr Tyr Thr Ala Asp Ala Leu Ile Ile Ala100 105 110Thr Gly Ala Gln Ala Lys Trp Leu Gly Ile Pro Thr Glu Gln Asp Phe115 120 125Met Gly Phe Gly Val Ser Ala Cys Ala Thr Cys Asp Gly Phe Phe Tyr130 135 140Arg Gly Lys Asp Val Ala Val Val Gly Gly Gly Asn Ser Ala Val Glu145 150 155 160Glu Ala Leu Tyr Leu Ser Asn Leu Ala Lys Ser Val Thr Val Ile His165 170 175Arg Arg Ser Asp Phe Arg Ala Glu Arg Ile Leu Arg Glu Arg Leu Leu180 185 190Gln Lys Asp Asn Val Arg Val Ile Trp Asp Thr Val Val Asp Glu Ile195 200 205Thr Gly Arg Pro Gly Lys Ala Pro Leu Pro Pro Ser Val Glu Gly Leu210 215 220Lys Leu Lys His Ala Val Thr Gly Ala Glu Thr His Leu Lys Val Asp225 230 235 240Gly Val Phe Val Ala Ile Gly His Ala Pro Ala Val Glu Leu Phe Val245 250 255Gly Lys Leu Lys Gln Lys Pro Asn Gly Tyr Leu Trp Thr Ala Pro Asn260 265 270Ser Thr Arg Thr Asp Val Pro Gly Val Phe Ala Ala Gly Asp Val Thr275 280 285Asp Asp Val Tyr Arg Gln Ala Val Thr Ala Ala Gly Leu Gly Cys Met290 295 300Ala Ala Leu Glu Ala Glu Lys Tyr Leu Ala Gly Ile Glu Val His Arg305 310 315 320Glu Ala Ala Glu210274211343212PRT213百脈根瘤菌400274Met Thr Gly Ile Ile Ser Thr Asp Val Leu Ile Val Gly Ala Gly Pro1 5 10 15Val Gly Leu Phe Ala Val Phe Glu Leu Gly Leu Phe Asp Met Lys Cys20 25 30His Leu Ile Asp Ile Leu Asp Lys Pro Gly Gly Gln Cys Ala Glu Leu35 40 45Tyr Pro Glu Lys Pro Ile Tyr Asp Ile Pro Gly Trp Pro Ser Ile Ser50 55 60Ala Gln Gly Leu Val Asp Lys Leu Leu Glu Gln Ile His Pro Phe Lys65 70 75 80Pro Asp Phe Thr Tyr Asn Arg Met Val Ser Ser Leu Glu Lys Leu Glu85 90 95Asp Gly Ser Phe Arg Val Thr Thr Asp Glu Asn Glu Val Phe Glu Ala100 105 110Lys Val Val Val Ile Ala Ala Gly Gly Gly Ser Phe Gln Pro Lys Arg115 120 125Pro Pro Ile Pro Gly Ile Glu Pro Tyr Glu Gly Lys Ser Val Phe Tyr130 135 140Ser Val Arg Arg Met Glu Asp Phe Arg Gly His Asp Leu Val Ile Val145 150 155 160Gly Gly Gly Asp Ser Ala Leu Asp Trp Thr Leu Asn Leu Gln Pro Val165 170 175Ala Lys Ser Val Thr Leu Val His Arg Arg Pro Glu Phe Arg Ala Ala180 185 190Pro Asp Ser Val Asn Lys Met Tyr Ala Met Gln Glu Met Lys Gln Leu195 200 205Glu Phe Arg Val Gly Gln Val Thr Gly Leu Thr Gly Ala Asp Gly Gln210 215 220Leu Ser Ser Ala Thr Ile Lys Gly Gly Pro Asp Gly Asp Ile Glu Val225 230 235 240Pro Cys Thr Arg Met Leu Pro Phe Phe Gly Leu Thr Met Lys Leu Gly245 250 255Pro Ile Ala Glu Trp Gly Leu Asn Leu His Glu Asn Leu Ile Pro Val260 265 270Asp Thr Glu Lys Phe Gln Thr Ser Val Pro Gly Ile Phe Ala Val Gly275 280 285Asp Ile Asn Ser Tyr Pro Gly Lys Leu Lys Leu Ile Leu Ser Gly Phe290 295 300His Glu Val Ala Leu Met Ala Gln Ala Ala Lys Arg Ile Val Ser Pro305 310 315 320Gly Glu Arg Ile Val Phe Gln Tyr Thr Thr Ser Ser Thr Ser Leu Gln325 330 335Lys Lys Leu Gly Val Val Gly34021027521115212PRT213啤酒糖酵母220221VARIANT2229，11223Xaa＝任何胺基酸400275VaL His Asn Ile Val Thr Ile Ile Xaa Ser Xaa Pro Ala Ala His1 5 10 15210276211104212PRT213金黃色葡萄球菌400276Met Ala Ile Val Lys Val Thr Asp Ala Asp Phe Asp Ser Lys Val Glu1 5 10 15Ser Gly Val Gln Leu Val Asp Phe Trp Ala Thr Trp Cys Gly Pro Cys20 25 30Lys Met Ile Ala Pro Val Leu Glu Glu Leu Ala Ala Asp Tyr Glu Gly35 40 45Lys Ala Asp Ile Leu Lys Leu Asp Val Asp Glu Asn Pro Ser Thr Ala50 55 60Ala Lys Tyr Glu Val Met Ser Ile Pro Thr Leu Ile Val Phe Lys Asp65 70 75 80Gly Gln Pro Val Asp Lys Val Val Gly Phe Gln Pro Lys Glu Asn Leu85 90 95Ala Glu Val Leu Asp Lys His Leu10021027721192212PRT213木糖葡萄球菌400277Met Ala Glu Gln Val Asp Phe Asp Ile Ala Ile Ile Gly Ala Gly Pro1 5 10 15Ala Gly Met Alr Ala Ala Val Tyr Ala Ser Arg Ala Asn Leu Ser Thr20 25 30Val Met Ile Glu Arg Gly Met Pro Gly Gly Gln Met Ala Asn Thr Glu35 40 45Glu Val Glu Asn Phe Pro Gly Phe Glu Met Val Thr Gly Pro Asp Leu50 55 60Ser Thr Lys Met Phe Glu His Ala Lys Lys Phe Gly Ala Lys Tyr Gln65 70 75 80Tyr Gly Asp Ile Lys Ser Ile Glu Asp Lys Gly Ser85 90210278211319212PRT213嗜酸熱原體400278Met Glu Phe Asn Leu His Ala Val Ser Ser Glu Glu Lys Glu Arg Asp1 5 10 15Phe Asp Val Val Ile Val Gly Ala Gly Ala Ala Gly Phe Ser Ala Ala20 25 30Val Tyr Ala Ala Arg Ser Gly Phe Ser Val Ala Ile Leu Asp Lys Ala35 40 45Val Ala Gly Gly Leu Thr Ala Glu Ala Pro Leu Val Glu Asn Tyr Leu50 55 60Gly Phe Lys Ser Ile Val Gly Ser Glu Leu Ala Lys Leu Phe Ala Asp65 70 75 80His Ala Ala Asn Tyr Ala Lys Ile Arg Glu Gly Val Glu Val Arg Ser85 90 95Ile Lys Lys Thr Gln Gly Gly Phe Asp Ile Glu Thr Asn Asp Asp Thr100 105 110Tyr His Ala Lys Tyr Val Ile Ile Thr Thr Gly Thr Thr His Lys His115 120 125Leu Gly Val Lys Gly Glu Ser Glu Tyr Phe Gly Lys Gly Thr Ser Tyr130 135 140Cys Ser Thr Cys Asp Gly Tyr Leu Phe Lys Gly Lys Arg Val Val Thr145 150 155 160Ile Gly Gly Gly Asn Ser Gly Ala Ile Ala Ala Ile Ser Met Ser Glu165 170 175Tyr Val Lys Asn Val Thr Ile Ile Glu Tyr Met Pro Lys Tyr Met Cys180 185 190Glu Asn Ala Tyr Val Gln Glu Ile Lys Lys Arg Asn Ile Pro Tyr Ile195 200 205Met Asn Ala Gln Val Thr Glu Ile Val Gly Asp Gly Lys Lys Val Thr210 215 220Gly Val Lys Tyr Lys Asp Arg Thr Thr Gly Glu Glu Lys Leu Ile Glu225 230 235 240Thr Asp Gly Val Phe Ile Tyr Val Gly Leu Ile Pro Gln Thr Ser Phe245 250 255Leu Lys Asp Ser Gly Val Lys Leu Asp Glu Arg Gly Tyr Ile Val Val260 265 270Asp Ser Arg Gln Arg Thr Ser Val Pro Gly Val Tyr Ala Ala Gly Asp275 280 285Val Thr Ser Gly Asn Phe Ala Gln Ile Ala Ser Ala Val Gly Asp Gly290 295 300Cys Lys Ala Ala Leu Ser Leu Tyr Ser Asp Ser Ile Ser Lys Lys305 310 315210279211317212PRT213海棲熱袍菌400279Met Val Phe Phe Asp Thr Gly Ser Leu Lys Lys Lys Glu Ile Lys Asp1 5 10 15Lys Tyr Asp Ile Val Val Val Gly Gly Gly Pro Ala Gly Leu Thr Ser20 25 30Ala Ile Tyr Ala Arg Arg Ala Gly Leu Ser Val Leu Val Val Glu Lys35 40 45Ala Ile Glu Gly Gly Tyr Val Asn Leu Thr His Leu Val Glu Asn Tyr50 55 60Pro Gly Phe Pro Ala Ile Ser Gly Glu Glu Leu Ala Ser Lys Phe Lys65 70 75 80Glu His Ala Glu Lys Phe Gly Ala Asp Ile Tyr Asn Ala Glu Val Val85 90 95Lys Leu Glu Val Gln Gly Asp Lys Lys Val Val Glu Leu Asp Asp Gly100 105 110Lys Arg Ile Glu Ala Pro Val Val Ile Val Ala Thr Gly Ala Asn Pro115 120 125Lys Lys Leu Asn Val Pro Gly Glu Lys Glu Phe Phe Gly Lys Gly Val130 135 140Ser Tyr Cys Ala Thr Cys Asp Gly Tyr Leu Phe Ala Gly Lys Asp Val145 150 155 160Ile Val Val Gly Gly Gly Asp Ser Ala Cys Asp Glu Ser Ile Phe Leu165 170 175Ser Asn Ile Val Asn Lys Ile Thr Met Ile Gln Leu Leu Glu Thr Leu180 185 190Thr Ala Ala Lys Val Leu Gln Glu Arg Val Leu Asn Asn Pro Lys Ile195 200 205Glu Val Ile Tyr Asn Ser Thr Val Arg Glu Ile Arg Gly Lys Asp Lys210 215 220Val Glu Glu Val Val Ile Glu Asn Val Lys Thr Gly Glu Thr Lys Val225 230 235 240Leu Lys Ala Asp Gly Val Phe Ile Phe Ile Gly Leu Asp Pro Asn Ser245 250 255Lys Leu Leu Glu Gly Leu Val Glu Leu Asp Pro Tyr Gly Tyr Val Ile260 265 270Thr Asp Glu Asn Met Glu Thr Ser Val Lys Gly Ile Tyr Ala Val Gly275 280 285Asp Val Arg Lys Lys Asn Leu Arg Gln Ile Val Thr Ala Val Ala Asp290 295 300Gly Ala Ile Ala Val Glu His Ala Ala Lys His Tyr Phe305 310 315210280211326212PRT213火山熱原體400280Met Asn Leu Tyr Arg Gly Met Glu Phe Asn Leu Arg Ser Val Ser Thr1 5 10 15Glu Ala Lys Glu Arg Asp Phe Asp Val Ile Ile Ile Gly Ala Gly Ala20 25 30Ala Gly Phe Ser Ala Ala Val Tyr Ala Ser Arg Ser Gly Leu Ser Ala35 40 45Val Ile Leu Asp Lys Asn Val Ala Gly Gly Leu Thr Ala Glu Ala Pro50 55 60Leu Val Glu Asn Tyr Leu Gly Phe Lys Ser Ile Val Gly Ser Asp Leu65 70 75 80Ala Lys Asn Phe Ala Glu His Ala Ser Glu Tyr Ala Ser Ile Arg Glu85 90 95Gly Val Glu Val Lys Ser Val Lys Lys Gly Asp Gly Gly Phe Ile Val100 105 110Asp Thr Ser Asp Gly Glu Tyr His Ser Lys Tyr Ile Ile Ile Thr Thr115 120 125Gly Thr Thr His Lys His Leu Gly Val Lys Gly Glu Ala Glu Tyr Phe130 135 140Gly Lys Gly Val Ser Tyr Cys Ser Thr Cys Asp Gly Tyr Leu Phe Lys145 150 155 160Asn Lys Asn Val Val Thr Ile Gly Gly Gly Asn Ser Gly Ala Ile Ala165 170 175Ala Ile Ser Met Ser Glu Tyr Val Lys Asn Ala Thr Ile Val Glu Tyr180 185 190Met Pro Arg Tyr Met Cys Glu Asn Ala Tyr Ile Glu Glu Ile Lys Lys195 200 205Arg Lys Ile Pro Tyr Ile Met Asn Ala Gln Val Thr Glu Ile Val Gly210 215 220Asp Gly Lys Lys Val Thr Gly Val Lys Tyr Lys Asp Arg Ser Ser Gly225 230 235 240Glu Glu Lys Thr Leu Pro Ala Asp Gly Val Phe Val Tyr Val Gly Leu245 250 255Ile Pro Gln Thr Ser Phe Leu Lys Asp Ser Gly Val Lys Leu Asp Glu260 265 270Arg Gly Tyr Ile Ile Val Asp Gly Arg Gln Arg Thr Asn Val Pro Gly275 280 285Ile Tyr Ala Ala Gly Asp Val Thr Ser Gly Ser Phe Ala Gln Ile Ala290 295 300Ser Ala Val Gly Asp Gly Cys Lys Ala Ala Leu Ser Leu Tyr Ser Asp305 310 315 320Thr Ile Ser Ser Lys Lys325210281211309212PRT213Ureaplasma parvum400281Met Asn Gln Glu Val Tyr Asp Leu Val Ile Ile Gly Ala Gly Pro Ala1 5 10 15Gly Leu Ala Ala Ala Val Tyr Ala Lys Arg Ser Gly Leu Asn Val Ile20 25 30Ile Val Glu Lys Gln Phe Pro Gly Gly Lys Ile Ala Leu Thr Ser Asn35 40 45Val Glu Asn Tyr Leu Gly Ile Asn Ser Ile Pro Gly Pro Glu Leu Ala50 55 60Tyr Lys Met Tyr Glu Gln Val Leu Asn Leu Asn Val Ser Ile Ile Tyr65 70 75 80Glu Ala Ala Asp Glu Ile Ser Leu Lys Glu Lys Tyr Lys Lys Ile Lys85 90 95Leu Thr Thr Gln Thr Leu Ile Thr Lys Thr Val Ile Ile Ala Thr Gly100 105 110Thr Glu Asn Arg Arg Leu Asn Ile Leu Gly Glu Leu Glu Phe Glu Asn115 120 125Lys Gly Ile Ser Tyr Cys Ala Ile Cys Asp Gly Pro Leu Tyr Lys Asn130 135 140Lys Ala Val Ser Val Ile Gly Ser Gly Asn Ser Ala Val Glu Glu Ala145 150 155 160Ile Tyr Leu Ala Thr Ile Ala Lys Glu Val His Leu Ile Ala Asn Lys165 170 175Pro Gln Phe Lys Ala Glu Gln Gln Leu Val Gln Ile Ala Asn Asn Thr180 185 190Pro Asn Ile Lys Ile Tyr Tyr Asn Lys Gln Thr Phe Glu Phe Phe Gly195 200 205His Gln Phe Leu Glu Gly Leu Lys Phe Arg Asp Leu Ile Thr Asn Glu210 215 220Val Thr Thr Leu Asn Ile Glu Ala Asn Phe Thr Phe Ile Gly Leu Leu225 230 235 240Pro Ser Arg Ile Asn Thr Asn Asn Leu Cys Ile Phe Asn Glu Val Asn245 250 255Gly Phe Ile Thr Thr Asp Lys Asn Met Gln Thr Ser Val Cys Gly Ile260 265 270Phe Ala Ala Gly Asp Ile Val Asp Lys Asn Val Arg Gln Ile Ala Thr
275 280 285Ala Thr Asn Asp Gly Val Ile Ala Ala Leu Tyr Ala Lys Glu Tyr Ile290 295 300Thr Arg Asn Asn Trp305210282211318212PRT213霍亂弧菌400282Met Ser Asn Val Lys His Ser Lys Leu Leu Ile Leu Gly Ser Gly Pro1 5 10 15Ala Gly Tyr Thr Ala Ala Val Tyr Ala Ala Arg Ala Asn Leu Lys Pro20 25 30Val Leu Val Thr Gly Met Gln Gln Gly Gly Gln Leu Thr Thr Thr Thr35 40 45Glu Val Glu Asn Trp Pro Gly Asp Ala Glu Gly Leu Thr Gly Pro Ala50 55 60Leu Met Glu Arg Met Lys Glu His Ala Glu Arg Phe Asp Thr Glu Ile65 70 75 80Val Phe Asp His Ile Asn Ser Val Asp Leu Ser Ser Arg Pro Phe Arg85 90 95Leu Thr Gly Asp Ser Gln Glu Tyr Thr Cys Asp Ala Leu Ile Ile Ser100 105 110Thr Gly Ala Ser Ala Lys Tyr Leu Gly Leu Glu Ser Glu Glu Ala Phe115 120 125Lys Gly Arg Gly Val Ser Ala Cys Ala Thr Cys Asp Gly Phe Phe Tyr130 135 140Arg Asn Gln Lys Val Ala Val Val Gly Gly Gly Asn Thr Ala Val Glu145 150 155 160Glu Ala Leu Tyr Leu Ser Asn Ile Ala Ser Glu Val His Leu Val His165 170 175Arg Arg Asp Ser Phe Arg Ser Glu Lys Ile Leu Ile Asp Arg Leu Met180 185 190Asp Lys Val Ala Asn Gly Asn Ile Val Leu His Thr His Arg Thr Leu195 200 205Asp Glu Val Leu Gly Asp Glu Met Gly Val Thr Gly Val Arg Leu Lys210 215 220Asp Thr Gln Ser Asp Met Thr Glu Asn Leu Asp Val Met Gly Val Phe225 230 235 240Ile Ala Ile Gly His Gln Pro Asn Ser Gln Ile Phe Glu Gly Gln Leu245 250 255Glu Met Lys Asn Gly Tyr Ile Val Val Lys Ser Gly Leu Glu Gly Asn260 265 270Ala Thr Gln Thr Ser Ile Glu Gly Val Phe Ala Ala Gly Asp Val Met275 280 285Asp His Asn Tyr Arg Gln Ala Ile Thr Ser Ala Gly Thr Gly Cys Met290 295 300Ala Ala Leu Asp Ala Glu Arg Tyr Leu Asp Ser Gln Gly Lys305 310 315210283211321212PRT213苛養木桿菌400283Met Ser Asp Tyr Pro Ala Ser Ala Lys His Ser Arg Leu Leu Ile Leu1 5 10 15Gly Ser Gly Pro Ala Gly Trp Thr Ala Ala Val Tyr Ala Ala Arg Ala20 25 30Asn Leu Gln Pro Val Leu Ile Thr Gly Leu Gln Gln Gly Gly Gln Leu35 40 45Met Thr Thr Thr Glu Val Asp Asn Trp Pro Gly Asp Ala His Gly Leu50 55 60Met Gly Pro Asp Leu Met Glu Arg Met Gln Ala His Ala Glu Arg Phe65 70 75 80Asp Thr Lys Val Ile Phe Asp Gln Ile Tyr Lys Ala Asp Leu Ser Thr85 90 95Arg Pro Phe Thr Leu Phe Gly Asp Ser Gly Leu Tyr Thr Cys Asp Gly100 105 110Leu Ile Ile Ala Thr Gly Ala Asn Ala Lys Tyr Leu Gly Ile Pro Ser115 120 125Glu Glu Ala Phe Lys Gly Arg Gly Val Ser Ala Cys Ala Thr Cys Asp130 135 140Gly Phe Phe Tyr Arg Asp Gln Asp Val Ala Val Ile Gly Gly Gly Asn145 150 155 160Thr Ala Val Glu Glu Ala Leu Tyr Leu Ser Asn Ile Ala Arg Lys Val165 170 175Tyr Leu Ile His Arg Arg Asp Lys Leu Arg Ala Glu Lys Ile Met Gln180 185 190Asn Lys Leu Phe Ser Lys Ala Ala Thr Gly Lys Ile Glu Leu Ile Trp195 200 205Asn Asn Ala Val Glu Glu Val Leu Gly Asn Asp Ala Ser Val Thr Gly210 215 220Val Arg Ile Arg Ser Thr Gln Asp Ser Ser Thr Arg Asp Ile Asp Val225 230 235 240Gln Gly Leu Phe Val Ala Ile Gly His His Pro Asn Thr Asp Leu Phe245 250 255Ala Gly Gln Leu Ala Met Asn Asn Gly Tyr Leu Gln Ile His Ser Gly260 265 270Thr Ala Gly Asn Val Thr Gln Thr Ser Val Glu Gly Val Phe Ala Ala275 280 285Gly Asp Val Ala Asp Gln His Tyr Arg Gln Ala Ile Thr Ser Ala Gly290 295 300Phe Gly Cys Met Ala Ala Leu Asp Ala Glu Arg Phe Leu Asp Lys Gly305 310 315 320Asn210284211318212PRT213運動發酵單胞菌400284Met Ser Ala Asp Pro Ile Ser Thr Arg Val Phe Ile Leu Gly Ser Gly1 5 10 15Pro Ala Gly Leu Thr Ala Ala Ile Tyr Ala Ala Arg Ala Gly Leu Asn20 25 30Pro Ile Val Ala Gln Gly Leu Gln Pro Gly Gly Gln Leu Thr Ile Thr35 40 45Thr Glu Val Glu Asn Phe Pro Gly Phe Arg Glu Pro Ile Gln Gly Pro50 55 60Trp Leu Met Glu Glu Met Gln Ala Gln Ala Glu Asn Val Gly Ala Lys65 70 75 80Leu Val Trp Asp Ile Ile Thr Ser Val Asp Phe Ser Gln Arg Pro Tyr85 90 95Arg Leu Met Gly Asp Gly Gly Gln Val Tyr Leu Ala Asp Ser Leu Ile100 105 110Ile Ser Thr Gly Ala Gln Ala Arg Trp Leu Gly Leu Glu Ser Glu Thr115 120 125Ala Leu Arg Gly Lys Gly Ile Ser Ala Cys Ala Thr Cys Asp Gly Phe130 135 140Phe Phe Arg Gly Lys Lys Val Val Val Ile Gly Gly Gly Asn Thr Ala145 150 155 160Val Glu Glu Ala Leu Tyr Leu Thr Asn His Ser Pro Glu Val Thr Leu165 170 175Ile His Arg Arg Asp Ser Leu Arg Ala Glu Lys Ile Met Gln Lys Arg
180 185 190Leu Leu Ala Asn Pro Lys Ile Lys Ile Arg Trp Asn Ser Glu Val Ala195 200 205Glu Phe Ile Ala Gly Glu Asp Ser Ala Leu Ser Ala Val Lys Leu Lys210 215 220Asp Thr Lys Thr Gly Glu Glu Ser Leu Leu Glu Thr Glu Gly Ala Phe225 230 235 240Ile Ala Ile Gly His Lys Pro Ala Thr Glu Leu Phe Gln Gly His Leu245 250 255Lys Leu Asp Asp Glu Gly Tyr Ile Glu Val Thr Pro Gly Thr Thr Gln260 265 270Thr Ser Ile Lys Gly Ile Phe Ala Cys Gly Asp Val Met Asp Lys His275 280 285Tyr Arg Gln Ala Val Thr Ala Ala Gly Thr Gly Cys Met Ala Ala Leu290 295 300Glu Ala Glu Arg Phe Leu Gly Glu Ile Asp Phe Lys Glu Asp305 310 315210285211122212PRT213Bos taurus400285Lys Leu Met His Gln Ala Ala Leu Leu Gly Gln Ala Leu Thr Asp Ser1 5 10 15Arg Lys Phe Gly Trp Glu Tyr Ser Gln Gln Val Arg His Ser Trp Ala20 25 30Thr Met Thr Glu Ala Ile Gln Ser His Ile Gly Ser Leu Ser Trp Gly35 40 45His Arg Leu Ala Leu Arg Glu Lys Ala Val Thr Tyr Val Asn Ser Phe50 55 60Gly Glu Phe Val Glu His His Lys Val Lys Ala Thr Asn Glu Lys Gly65 70 75 80Gln Glu Val Leu Tyr Thr Ala Ala Lys Phe Val Ile Ala Thr Gly Glu85 90 95Arg Pro Arg Tyr Leu Gly Ile Pro Gly Asp Arg Glu Tyr Cys Ile Thr100 105 110Ser Asp Asp Leu Phe Ser Leu Pro Tyr Cys115 120210286211511212PRT213Bos taurus400286Met Ala Ala Leu Arg Gly Ala Ala Ala Arg Phe Arg Gly Arg Ala Pro1 5 10 15Gly Gly Ala Arg Gly Ala Ala Gly Arg Gln Cys Tyr Asp Leu Leu Val20 25 30Ile Gly Gly Gly Ser Gly Gly Leu Ala Cys Ala Lys Glu Ala Ala Gln35 40 45Leu Gly Lys Lys Val Ala Val Leu Asp Tyr Val Glu Pro Ser Pro Gln50 55 60Gly Thr Arg Trp Gly Leu Gly Gly Thr Cys Val Asn Val Gly Cys Ile65 70 75 80Pro Lys Lys Leu Met His Gln Ala Ala Leu Leu Gly Gly Met Ile Arg85 90 95Asp Ala Pro His Tyr Gly Trp Gly Val Ala Gln Ala Pro His Ser Trp100 105 110Ala Thr Leu Ala Asp Ala Val Gln Asn His Val Lys Ser Leu Asn Trp115 120 125Gly His Arg Ile Gln Leu Gln Asp Arg Lys Val Lys Tyr Phe Asn Val130 135 140Lys Ala Ser Phe Val Asp Thr His Thr Val Cys Gly Val Ser Lys Gly145 150 155 160Gly Glu Glu Thr Leu Leu Ser Ala Glu His Ile Val Ile Ala Thr Gly165 170175Gly Arg Pro Arg Tyr Pro Thr His Ile Glu Gly Ala Leu Glu Tyr Gly180 185 190Ile Thr Ser Asp Asp Leu Phe Trp Leu Lys Glu Ser Pro Gly Lys Thr195 200 205Leu Val Val Gly Ala Ser Tyr Val Ala Leu Glu Cys Ala Gly Leu Leu210 215 220Thr Gly Leu Gly Leu Asp Thr Thr Val Met Ile Arg Ser Val Pro Leu225 230 235 240Arg Ala Phe Asp Gln Gln Met Ala Ser Leu Val Thr Glu His Met Ala245 250 255Gly His Gly Thr Arg Ile Leu Arg Gly Cys Ala Pro Glu Lys Val Glu260 265 270Lys Leu Pro Gly Gln Gln Leu Arg Val Thr Trp Val Asp Leu Thr Ser275 280 285Asp Arg Lys Asp Ala Gly Thr Phe Asp Thr Val Leu Trp Ala Ile Gly290 295 300Arg Val Pro Glu Thr Ala Ser Leu Asn Leu Glu Lys Ala Gly Val His305 310 315 320Thr Asn Pro Val Thr Gly Lys Ile Leu Val Asp Ala Gln Glu Thr Thr325 330 335Ser Val Pro His Ile Tyr Ala Ile Gly Asp Val Ala Glu Gly Arg Pro340 345 350Glu Leu Thr Pro Thr Ala Ile Met Ala Gly Arg Leu Leu Ala Gln Arg355 360 365Leu Ser Gly Arg Thr Ser Asp Leu Met Asp Tyr Ser Ser Val Pro Thr370 375 380Thr Val Phe Thr Pro Leu Glu Tyr Gly Cys Val Gly Leu Ser Glu Glu385 390 395 400Ala Ala Val Ala Arg His Gly Glu Glu His Val Glu Val Tyr His Ala405 410 415Phe Tyr Lys Pro Leu Glu Phe Thr Val Pro Gln Arg Asp Ala Ser Gln420 425 430Cys Tyr Ile Lys Met Val Cys Leu Arg Glu Pro Pro Gln Leu Val Leu435 440 445Gly Leu His Phe Leu Gly Pro Asn Ala Gly Glu Val Ile Gln Gly Phe450 455 460Ala Leu Gly Ile Lys Cys Gly Ala Ser Tyr Gln Gln Leu Met Arg Thr465 470 475 480Val Gly Ile His Pro Thr Cys Ala Glu Glu Val Ala Lys Leu Arg Ile485 490 495Ser Lys Arg Ser Gly Leu Asp Pro Thr Val Thr Gly Cys Cys Gly500 505 510210287211525212PRT213Caenorhabditis elegans220221VARIANT222524223Xaa＝任何胺基酸400287Met Tyr Ile Lys Gly Asn Ala Val Gly Gly Leu Lys Glu Leu Lys Ala1 5 10 15Leu Lys Gln Asp Tyr Leu Lys Glu Trp Leu Arg Asp His Thr Tyr Asp20 25 30Leu Ile Val Ile Gly Gly Gly Ser Gly Gly Leu Ala Ala Ala Lys Glu35 40 45Ala Ser Arg Leu Gly Lys Lys Val Ala Cys Leu Asp Phe Val Lys Pro50 55 60Ser Pro Gln Gly Thr Ser Trp Gly Leu Gly Gly Thr Cys Val Asn Val65 70 75 80Gly Cys Ile Pro Lys Lys Leu Met His Gln Ala Ser Leu Leu Gly His85 90 95Ser Ile His Asp Ala Lys Lys Tyr Gly Trp Lys Leu Pro Glu Gly Lys100 105 110Val Glu His Gln Trp Asn His Leu Arg Asp Ser Val Gln Asp His Ile115 120 125Ala Ser Leu Asn Trp Gly Tyr Arg Val Gln Leu Arg Glu Lys Thr Val130 135 140Thr Tyr Ile Asn Ser Tyr Gly Glu Phe Thr Gly Pro Phe Glu Ile Ser145 150 155 160Ala Thr Asn Lys Lys Lys Lys Val Glu Lys Leu Thr Ala Asp Arg Phe165 170 175Leu Ile Ser Thr Gly Leu Arg Pro Lys Tyr Pro Glu Ile Pro Gly Val180 185 190Lys Glu Tyr Thr Ile Thr Ser Asp Asp Leu Phe Gln Leu Pro Tyr Ser195 200 205Pro Gly Lys Thr Leu Cys Val Gly Ala Ser Tyr Val Ser Leu Glu Cys210 215 220Ala Gly Phe Leu His Gly Phe Gly Phe Asp Val Thr Val Met Val Arg225 230 235 240Ser Ile Leu Leu Arg Gly Phe Asp Gln Asp Met Ala Glu Arg Ile Arg245 250 255Lys His Met Ile Ala Tyr Gly Met Lys Phe Glu Ala Gly Val Pro Thr260 265 270Arg Ile Glu Gln Ile Asp Glu Lys Thr Asp Glu Lys Ala Gly Lys Tyr275 280 285Arg Val Phe Trp Pro Lys Lys Asn Glu Glu Thr Gly Glu Met Gln Glu290 295 300Val Ser Glu Glu Tyr Asn Thr Ile Leu Met Ala Ile Gly Arg Glu Ala305 310 315 320Val Thr Asp Asp Val Gly Leu Thr Thr Ile Gly Val Glu Arg Ala Lys325 330 335Ser Lys Lys Val Leu Gly Arg Arg Glu Gln Ser Thr Thr Ile Pro Trp340 345 350Val Tyr Ala Ile Gly Asp Val Leu Glu Gly Thr Pro Glu Leu Thr Pro355 360 365Val Ala Ile Gln Ala Gly Arg Val Leu Met Arg Arg Ile Phe Asp Gly370 375 380Ala Asn Glu Leu Thr Glu Tyr Asp Gln Ile Pro Thr Thr Val Phe Thr385 390 395 400Pro Leu Glu Tyr Gly Cys Cys Gly Leu Ser Glu Glu Asp Ala Met Met405 410 415Lys Tyr Gly Lys Asp Asn Ile Ile Ile Tyr His Asn Val Phe Asn Pro420 425 430Leu Glu Tyr Thr Ile Ser Glu Arg Met Asp Lys Asp His Cys Tyr Leu435 440 445Lys Met Ile Cys Leu Arg Asn Glu Glu Glu Lys Val Val Gly Phe His450 455 460Ile Leu Thr Pro Asn Ala Gly Glu Val Thr Gln Gly Phe Gly Ile Ala465 470 475 480Leu Lys Leu Ala Ala Lys Lys Ala Asp Phe Asp Arg Leu Ile Gly Ile485 490 495His Pro Thr Val Ala Glu Asn Phe Thr Thr Leu Thr Leu Glu Lys Lys500 505 510Glu Gly Asp Glu Glu Leu Gln Ala Ser Gly Cys Xaa Gly515 520 525210288211667212PRT213Caenorhabditis elegans220221VARIANT222666223Xaa＝任何胺基酸400288Met Lys Ser Leu Thr Glu Leu Phe Gly Cys Phe Lys Arg Gln Pro Arg1 5 10 15Gln Gln Glu Ala Ser Ser Pro Ala Asn Pro His Val Ser Asp Thr Leu20 25 30Ser Met Gly Val Ala Ala Ser Gly Met Pro Pro Pro Lys Arg Pro Ala35 40 45Pro Ala Glu Ser Pro Thr Leu Pro Gly Glu Thr Leu Val Asp Ala Pro50 55 60Gly Ile Pro Leu Lys Glu Ala Leu Lys Glu Ala Ala Asn Ser Lys Ile65 70 75 80Val Ile Phe Tyr Asn Ser Ser Asp Glu Glu Lys Gln Leu Val Glu Phe85 90 95Glu Thr Tyr Leu Asn Ser Leu Lys Glu Pro Ala Asp Ala Glu Lys Pro100 105 110Leu Glu Ile Pro Glu Ile Lys Lys Leu Gln Val Ser Arg Ala Ser Gln115 120 125Lys Val Ile Gln Tyr Leu Thr Leu His Thr Ser Trp Pro Leu Met Tyr130 135 140Ile Lys Gly Asn Ala Val Gly Gly Leu Lys Glu Leu Lys Ala Leu Lys145 150 155 160Gln Asp Tyr Leu Lys Glu Trp Leu Arg Asp His Thr Tyr Asp Leu Ile165 170 175Val Ile Gly Gly Gly Ser Gly Gly Leu Ala Ala Ala Lys Glu Ala Ser180 185 190Arg Leu Gly Lys Lys Val Ala Cys Leu Asp Phe Val Lys Pro Ser Pro195 200 205Gln Gly Thr Ser Trp Gly Leu Gly Gly Thr Cys Val Asn Val Gly Cys210 215 220Ile Pro Lys Lys Leu Met His Gln Ala Ser Leu Leu Gly His Ser Ile225 230 235 240His Asp Ala Lys Lys Tyr Gly Trp Lys Leu Pro Glu Gly Lys Val Glu245 250 255His Gln Trp Asn His Leu Arg Asp Ser Val Gln Asp His Ile Ala Ser260 265 270Leu Asn Trp Gly Tyr Arg Val Gln Leu Arg Glu Lys Thr Val Thr Tyr275 280 285Ile Asn Ser Tyr Gly Glu Phe Thr Gly Pro Phe Glu Ile Ser Ala Thr290 295 300Asn Lys Lys Lys Lys Val Glu Lys Leu Thr Ala Asp Arg Phe Leu Ile305 310 315 320Ser Thr Gly Leu Arg Pro Lys Tyr Pro Glu Ile Pro Gly Val Lys Glu325 330 335Tyr Thr Ile Thr Ser Asp Asp Leu Phe Gln Leu Pro Tyr Ser Pro Gly340 345 350Lys Thr Leu Cys Val Gly Ala Ser Tyr Val Ser Leu Glu Cys Ala Gly355 360 365Phe Leu His Gly Phe Gly Phe Asp Val Thr Val Met Val Arg Ser Ile370 375 380Leu Leu Arg Gly Phe Asp Gln Asp Met Ala Glu Arg Ile Arg Lys His385 390 395 400Met Ile Ala Tyr Gly Met Lys Phe Glu Ala Gly Val Pro Thr Arg Ile405 410 415Glu Gln Ile Asp Glu Lys Thr Asp Glu Lys Ala Gly Lys Tyr Arg Val420 425 430Phe Trp Pro Lys Lys Asn Glu Glu Thr Gly Glu Met Gln Glu Val Ser435 440 445Glu Glu Tyr Asn Thr Ile Leu Met Ala Ile Gly Arg Glu Ala Val Thr450 455 460Asp Asp Val Gly Leu Thr Thr Ile Gly Val Glu Arg Ala Lys Ser Lys465 470 475 480Lys Val Leu Gly Arg Arg Glu Gln Ser Thr Thr Ile Pro Trp Val Tyr485 490 495Ala Ile Gly Asp Val Leu Glu Gly Thr Pro Glu Leu Thr Pro Val Ala
500 505 510Ile Gln Ala Gly Arg Val Leu Met Arg Arg Ile Phe Asp Gly Ala Asn515 520 525Glu Leu Thr Glu Tyr Asp Gln Ile Pro Thr Thr Val Phe Thr Pro Leu530 535 540Glu Tyr Gly Cys Cys Gly Leu Ser Glu Glu Asp Ala Met Met Lys Tyr545 550 555 560Gly Lys Asp Asn Ile Ile Ile Tyr His Asn Val Phe Asn Pro Leu Glu565 570 575Tyr Thr Ile Ser Glu Arg Met Asp Lys Asp His Cys Tyr Leu Lys Met580 585 590Ile Cys Leu Arg Asn Glu Glu Glu Lys Val Val Gly Phe His Ile Leu595 600 605Thr Pro Asn Ala Gly Glu Val Thr Gln Gly Phe Gly Ile Ala Leu Lys610 615 620Leu Ala Ala Lys Lys Ala Asp Phe Asp Arg Leu Ile Gly Ile His Pro625 630 635 640Thr Val Ala Glu Asn Phe Thr Thr Leu Thr Leu Glu Lys Lys Glu Gly645 650 655Asp Glu Glu Leu Gln Ala Ser Gly Cys Xaa Gly660 665210289211516212PRT213黃果蠅400289Met Ser Thr Ile Lys Phe Leu Arg Ser Ser Thr His Asn Ala Leu Arg1 5 10 15Ser Ser Leu Gly Trp Cys Arg Leu Ala Ala Ser Arg Pro Arg Tyr Asp20 25 30Tyr Asp Leu Val Val Leu Gly Gly Gly Ser Ala Gly Leu Ala Cys Ala35 40 45Lys Glu Ala Ala Gly Cys Gly Ala Arg Val Leu Cys Phe Asp Tyr Val50 55 60Lys Pro Thr Pro Val Gly Thr Lys Trp Gly Ile Gly Gly Thr Cys Val65 70 75 80Asn Val Gly Cys Ile Pro Lys Lys Leu Met His Gln Ala Ser Leu Leu85 90 95Gly Glu Ala Val His Glu Ala Val Ala Tyr Gly Trp Asn Val Asp Asp100 105 110Thr Asn Ile Arg Pro Asp Trp Arg Lys Leu Val Arg Ser Val Gln Asn115 120 125His Ile Lys Ser Val Asn Trp Val Thr Arg Val Asp Leu Arg Asp Lys130 135 140Lys Val Glu Tyr Val Asn Ser Met Ala Thr Phe Arg Asp Ser His Thr145 150 155 160Ile Glu Tyr Val Ala Met Pro Gly Ala Glu His Arg Gln Val Thr Ser165 170 175Glu Tyr Val Val Val Ala Val Gly Gly Arg Pro Arg Tyr Pro Asp Ile180 185 190Pro Gly Ala Val Glu Leu Gly Ile Thr Ser Asp Asp Ile Phe Ser Tyr195 200 205Glu Arg Glu Pro Gly Arg Thr Leu Val Val Gly Ala Gly Tyr Val Gly210 215 220Leu Glu Cys Ala Cys Phe Leu Lys Gly Leu Gly Tyr Glu Pro Thr Val225 230 235 240Met Val Arg Ser Ile Val Leu Arg Gly Phe Asp Arg Gln Met Ser Glu245 250 255Leu Leu Ala Ala Met Met Thr Glu Arg Gly Ile Pro Phe Leu Gly Thr260 265 270Thr Ile Pro Lys Ala Val Glu Arg Gln Ala Asp Gly Arg Leu Leu Val275 280 285Arg Tyr Arg Asn Thr Thr Thr Gln Met Asp Gly Ser Asp Val Phe Asp290 295 300Thr Val Leu Trp Ala Ile Gly Arg Lys Gly Leu Ile Glu Asp Leu Asn305 310 315 320Leu Asp Ala Ala Gly Val Lys Thr His Asp Asp Lys Ile Val Val Asp325 330 335Ala Ala Glu Ala Thr Ser Val Pro His Ile Phe Ala Val Gly Asp Ile340 345 350Ile Tyr Gly Arg Pro Glu Leu Thr Pro Val Ala Ile Leu Ser Gly Arg355 360 365Leu Leu Ala Arg Arg Leu Phe Ala Gly Ser Thr Gln Leu Met Asp Tyr370 375 380Ala Asp Val Ala Thr Thr Val Phe Thr Pro Leu Glu Tyr Ser Cys Val385 390 395 400Gly Met Ser Glu Glu Thr Ala Ile Glu Leu Arg Gly Ala Asp Asn Ile405 410 415Glu Val Phe His Gly Tyr Tyr Lys Pro Thr Glu Phe Phe Ile Pro Gln420 425 430Lys Ser Val Arg His Cys Tyr Leu Lys Ala Val Ala Glu Val Ser Gly435 440 445Asp Gln Lys Ile Leu Gly Leu His Tyr Ile Gly Pro Val Ala Gly Glu450 455 460Val Ile Gln Gly Phe Ala Ala Ala Leu Lys Thr Gly Leu Thr Val Lys465 470 475 480Thr Leu Leu Asn Thr Val Gly Ile His Pro Thr Thr Ala Glu Glu Phe485 490 495Thr Arg Leu Ser Ile Thr Lys Arg Ser Gly Arg Asp Pro Thr Pro Ala500 505 510Ser Cys Cys Ser515210290211524212PRT213人220221VARIANT222523223Xaa＝任何胺基酸400290Met Ala Ala Met Ala Val Ala Leu Arg Gly Leu Gly Gly Arg Phe Arg1 5 10 15Trp Arg Thr Gln Ala Val Ala Gly Gly Val Arg Gly Ala Ala Arg Gly20 25 30Ala Ala Ala Gly Gln Arg Asp Tyr Asp Leu Leu Val Val Gly Gly Gly35 40 45Ser Gly Gly Leu Ala Cys Ala Lys Glu Ala Ala Gln Leu Gly Arg Lys50 55 60Val Ser Val Val Asp Tyr Val Glu Pro Ser Pro Gln Gly Thr Arg Trp65 70 75 80Gly Leu Gly Gly Thr Cys Val Asn Val Gly Cys Ile Pro Lys Lys Leu85 90 95Met His Gln Ala Ala Leu Leu Gly Gly Leu Ile Gln Asp Ala Pro Asn100 105 110Tyr Gly Trp Glu Val Ala Gln Pro Val Pro His Asp Trp Arg Lys Met115 120 125Ala Glu Ala Val Gln Asn His Val Lys Ser Leu Asn Trp Gly His Arg130 135 140Val Gln Leu Gln Asp Arg Lys Val Lys Tyr Phe Asn Ile Lys Ala Ser145 150 155 160Phe Val Asp Glu His Thr Val Cys Gly Val Ala Lys Gly Gly Lys Glu165 170 175Ile Leu Leu Ser Ala Asp His Ile Ile Ile Ala Thr Gly Gly Arg Pro180 185 190Arg Tyr Pro Thr His Ile Glu Gly Ala Leu Glu Tyr Gly Ile Thr Ser195 200 205Asp Asp Ile Phe Trp Leu Lys Glu Ser Pro Gly Lys Thr Leu Val Val210 215 220Gly Ala Ser Tyr Val Ala Leu Glu Cys Ala Gly Phe Leu Thr Gly Ile225 230 235 240Gly Leu Asp Thr Thr Ile Met Met Arg Ser Ile Pro Leu Arg Gly Phe245 250 255Asp Gln Gln Met Ser Ser Met Val Ile Glu His Met Ala Ser His Gly260 265 270Thr Arg Phe Leu Arg Gly Cys Ala Pro Ser Arg Val Arg Arg Leu Pro275 280 285Asp Gly Gln Leu Gln Val Thr Trp Glu Asp Ser Thr Thr Gly Lys Glu290 295 300Asp Thr Gly Thr Phe Asp Thr Val Leu Trp Ala Ile Gly Arg Val Pro305 310 315 320Asp Thr Arg Ser Leu Asn Leu Glu Lys Ala Gly Val Asp Thr Ser Pro325 330 335Asp Thr Gln Lys Ile Leu Val Asp Ser Arg Glu Ala Thr Ser Val Pro340 345 350His Ile Tyr Ala Ile Gly Asp Val Val Glu Gly Arg Pro Glu Leu Thr355 360 365Pro Ile Ala Ile Met Ala Gly Arg Leu Leu Val Gln Arg Leu Phe Gly370 375 380Gly Ser Ser Asp Leu Met Asp Tyr Asp Asn Val Pro Thr Thr Val Phe385 390 395 400Thr Pro Leu Glu Tyr Gly Cys Val Gly Leu Ser Glu Glu Glu Ala Val405 410 415Ala Arg His Gly Gln Glu His Val Glu Val Tyr His Ala His Tyr Lys420 425 430Pro Leu Glu Phe Thr Val Ala Gly Arg Asp Ala Ser Gln Cys Tyr Val435 440 445Lys Met Val Cys Leu Arg Glu Pro Pro Gln Leu Val Leu Gly Leu His450 455 460Phe Leu Gly Pro Asn Ala Gly Glu Val Thr Gln Gly Phe Ala Leu Gly465 470 475 480Ile Lys Cys Gly Ala Ser Tyr Ala Gln Val Met Arg Thr Val Gly Ile485 490 495His Pro Thr Cys Ser Glu Glu Val Val Lys Leu Arg Ile Ser Lys Arg500 505 510Ser Gly Leu Asp Pro Thr Val Thr Gly Cys Xaa Gly515 520210291211497212PRT213人400291Met Asn Gly Pro Glu Asp Leu Pro Lys Ser Tyr Asp Tyr Asp Leu Ile1 5 10 15Ile Ile Gly Gly Gly Ser Gly Gly Leu Ala Ala Ala Lys Glu Ala Ala20 25 30Gln Tyr Gly Lys Lys Val Met Val Leu Asp Phe Val Thr Pro Thr Pro35 40 45Leu Gly Thr Arg Trp Gly Leu Gly Gly Thr Cys Val Asn Val Gly Cys50 55 60Ile Pro Lys Lys Leu Met His Gln Ala Ala Leu Leu Gly Gln Ala Leu65 70 75 80Gln Asp Ser Arg Asn Tyr Gly Trp Lys Val Glu Glu Thr Val Lys His85 90 95Asp Trp Asp Arg Met Ile Glu Ala Val Gln Asn His Ile Gly Ser Leu100 105 110Asn Trp Gly Tyr Arg Val Ala Leu Arg Glu Lys Lys Val Val Tyr Glu115 120 125Asn Ala Tyr Gly Gln Phe Ile Gly Pro His Arg Ile Lys Ala Thr Asn130 135 140Asn Lys Gly Lys Glu Lys Ile Tyr Ser Ala Glu Arg Phe Leu Ile Ala145 150 155 160Thr Gly Glu Arg Pro Arg Tyr Leu Gly Ile Pro Gly Asp Lys Glu Tyr165 170 175Cys Ile Ser Ser Asp Asp Leu Phe Ser Leu Pro Tyr Cys Pro Gly Lys180 185 190Thr Leu Val Val Gly Ala Ser Tyr Val Ala Leu Glu Cys Ala Gly Phe195 200 205Leu Ala Gly Ile Gly Leu Asn ValThr Val Met Val Arg Ser Ile Leu210 215 220Leu Arg Gly Phe Asp Gln Asp Met Ala Asn Lys Ile Gly Glu His Met225 230 235 240Glu Glu His Gly Ile Lys Phe Ile Arg Gln Phe Val Pro Ile Lys Val245 250 255Glu Gln Ile Glu Ala Gly Thr Pro Gly Arg Leu Arg Val Val Ala Gln260 265 270Ser Thr Asn Ser Glu Glu Ile Ile Glu Gly Glu Tyr Asn Thr Val Met275 280 285Leu Ala Ile Gly Arg Asp Ala Cys Thr Arg Lys Ile Gly Leu Glu Thr290 295 300Val Gly Val Lys Ile Asn Glu Lys Thr Gly Lys Ile Pro Val Thr Asp305 310 315 320Glu Glu Gln Thr Asn Val Pro Tyr Ile Tyr Ala Ile Gly Asp Ile Leu325 330 335Glu Asp Lys Val Glu Leu Thr Pro Val Ala Ile Gln Ala Gly Arg Leu340 345 350Leu Ala Gln Arg Leu Tyr Ala Gly Ser Thr Val Lys Cys Asp Tyr Glu355 360 365Asn Val Pro Thr Thr Val Phe Thr Pro Leu Glu Tyr Gly Ala Cys Gly370 375 380Leu Ser Glu Glu Lys Ala Val Glu Lys Phe Gly Glu Glu Asn Ile Glu385 390 395 400Val Tyr His Ser Tyr Phe Trp Pro Leu Glu Trp Thr Ile Pro Ser Arg405 410 415Asp Asn Asn Lys Cys Tyr Ala Lys Ile Ile Cys Asn Thr Lys Asp Asn420 425 430Glu Arg Val Val Gly Phe His Val Leu Gly Pro Asn Ala Gly Glu Val435 440 445Thr Gln Gly Phe Ala Ala Ala Leu Lys Cys Gly Leu Thr Lys Lys Gln450 455 460Leu Asp Ser Thr Ile Gly Ile His Pro Val Cys Ala Glu Val Phe Thr465 470 475 480Thr Leu Ser Val Thr Lys Arg Ser Gly Ala Arg Ile Leu Gln Ala Gly485 490 495Cys210292211497212PRT213人400292Met Asn Gly Pro Glu Asp Leu Pro Lys Ser Tyr Asp Tyr Asp Leu Ile1 5 10 15Ile Ile Gly Gly Gly Ser Gly Gly Leu Ala Ala Ala Lys Glu Pro Ala20 25 30Gln Tyr Gly Lys Lys Val Met Val Leu Asp Phe Gly Thr Pro Thr pro35 40 45Leu Gly Thr Arg Trp Gly Leu Gly Gly Thr Cys Val Asn Val Gly Cys50 55 60Ile Pro Lys Lys Leu Met His Gln Ala Ala Leu Leu Gly Gln Ala Leu65 70 75 80Gln Asp Ser Arg Asn Tyr Gly Trp Lys Val Glu Glu Thr Val Lys His85 90 95Asp Trp Asp Arg Met Ile Glu Ala Val Gln Asn His Ile Gly Ser Leu100 105 110Asn Trp Gly Tyr Arg Val Ala Leu Arg Glu Lys Lys Val Val Tyr Glu115 120 125Asn Ala Tyr Gly Gln Phe Ile Gly Pro His Arg Ile Lys Ala Thr Asn130 135 140Asn Lys Gly Lys Glu Lys Ile Tyr Ser Ala Glu Arg Phe Leu Ile Ala145 150 155 160Thr Gly Glu Arg Pro Arg Tyr Leu Gly Ile Pro Gly Asp Lys Glu Tyr165 170 175Cys Ile Ser Ser Asp Asp Leu Phe Ser Leu Pro Tyr Cys Pro Gly Lys180 185 190Thr Leu Val Val Gly Ala Ser Tyr Val Ala Leu Glu Cys Ala Gly Phe195 200 205Leu Ala Gly Ile Gly Leu Asp Val Thr Val Met Val Arg Ser Ile Leu210 215 220Leu Arg Gly Phe Asp Gln Asp Met Ala Asn Lys Ile Gly Glu His Met225 230 235 240Glu Glu His Gly Ile Lys Phe Ile Arg Gln Phe Val Pro Ile Lys Val245 250 255Glu Gln Ile Glu Ala Gly Thr Pro Gly Arg Leu Arg Val Val Ala Gln260 265 270Ser Thr Asn Ser Glu Glu Ile Ile Glu Gly Glu Tyr Asn Thr Val Met275 280 285Leu Ala Ile Gly Arg Asp Ala Cys Thr Arg Lys Ile Gly Leu Glu Thr290 295 300Val Gly Val Lys Ile Asn Glu Lys Thr Gly Lys Ile Pro Val Thr Asp305 310 315 320Glu Glu Gln Thr Asn Val Pro Tyr Ile Tyr Ala Ile Gly Asp Ile Leu325 330 335Glu Asp Lys Val Glu Leu Thr Pro Val Ala Ile Gln Ala Gly Arg Leu340 345 350Leu Ala Gln Arg Leu Tyr Ala Gly Ser Thr Val Lys Cys Asp Tyr Glu355 360 365Asn Val Pro Thr Thr Val Phe Thr Pro Leu Glu Tyr Gly Ala Cys Gly370 375 380Leu Ser Glu Glu Lys Ala Val Glu Lys Phe Gly Glu Glu Asn Ile Glu385 390 395 400Val Tyr His Ser Tyr Phe Trp Pro Leu Glu Trp Thr Ile Pro Ser Arg405 410 415Asp Asn Asn Lys Cys Tyr Ala Lys Ile Ile Cys Asn Thr Lys Asp Asn420 425 430Glu Arg Val Val Gly Phe His Val Leu Gly Pro Asn Ala Gly Glu Val435 440 445Thr Gln Gly Phe Ala Ala Ala Leu Lys Cys Gly Leu Thr Lys Lys Gln450 455 460Leu Asp Ser Thr Ile Gly Ile His Pro Val Cys Ala Glu Val Phe Thr465 470 475 480Thr Leu Ser Val Thr Lys Arg Ser Gly Ala Ser Ile Leu Gln Ala Gly485 490 495Cys210293211521212PRT213人220221VARIANT222520223Xaa＝任何胺基酸400293Met Ala Val Ala Leu Arg Gly Leu Gly Gly Arg Phe Arg Trp Arg Thr1 5 10 15Gln Ala Val Ala Gly Gly Val Arg Gly Ala Ala Arg Gly Ala Ala Ala20 25 30Gly Gln Arg Asp Tyr Asp Leu Leu Val Val Gly Gly Gly Ser Gly Gly35 40 45Leu Ala Cys Ala Lys Glu Ala Ala Gln Leu Gly Arg Lys Val Ala Val50 55 60Val Asp Tyr Val Glu Pro Ser Pro Gln Gly Thr Arg Trp Gly Leu Gly65 70 75 80Gly Thr Cys Val Asn Val Gly Cys Ile Pro Lys Lys Leu Met His Gln85 90 95Ala Ala Leu Leu Gly Gly Leu Ile Gln Asp Ala Pro Asn Tyr Gly Trp100 105 110Glu Val Ala Gln Pro Val Pro His Asp Trp Arg Lys Met Ala Glu Ala115 120 125Val Gln Asn His Val Lys Ser Leu Asn Trp Gly His Arg Val Gln Leu130 135 140Gln Asp Arg Lys Val Lys Tyr Phe Asn Ile Lys Ala Ser Phe Val Asp145 150 155 160Glu His Thr Val Cys Gly Val Ala Lys Gly Gly Lys Glu Ile Leu Leu165 170 175Ser Ala Asp His Ile Ile Ile Ala Thr Gly Gly Arg Pro Arg Tyr Pro180 185 190Thr His Ile Glu Gly Ala Leu Glu Tyr Gly Ile Thr Ser Asp Asp Ile195 200 205Phe Trp Leu Lys Glu Ser Pro Gly Lys Thr Leu Val Val Gly Ala Ser210 215 220Tyr Val Ala Leu Glu Cys Ala Gly Phe Leu Thr Gly Ile Gly Leu Asp225 230 235 240Thr Thr Ile Met Met Arg Ser Ile Pro Leu Arg Gly Phe Asp Gln Gln245 250 255Met Ser Ser Met Val Ile Glu His Met Ala Ser His Gly Thr Arg Phe260 265 270Leu Arg Gly Cys Ala Pro Ser Arg Val Arg Arg Leu Pro Asp Gly Gln275 280 285Leu Gln Val Thr Trp Glu Asp Ser Thr Thr Gly Lys Glu Asp Thr Gly290 295 300Thr Phe Asp Thr Val Leu Trp Ala Ile Gly Arg Val Pro Asp Thr Arg305 310 315 320Ser Leu Asn Leu Glu Lys Ala Gly Val Asp Thr Ser Pro Asp Thr Gln325 330 335Lys Ile Leu Val Asp Ser Arg Glu Ala Thr Ser Val Pro His Ile Tyr340 345 350Ala Ile Gly Asp Val Val Glu Gly Arg Pro Glu Leu Thr Pro Ile Ala355 360 365Ile Met Ala Gly Arg Leu Leu Val Gln Arg Leu Phe Gly Gly Ser Ser370 375 380Asp Leu Met Asp Tyr Asp Asn Val Pro Thr Thr Val Phe Thr Pro Leu385 390 395 400Glu Tyr Gly Cys Val Gly Leu Ser Glu Glu Glu Ala Val Ala Arg His405 410 415Gly Gln Glu His Val Glu Val Tyr His Ala His Tyr Lys Pro Leu Glu420 425 430Phe Thr Val Ala Gly Arg Asp Ala Ser Gln Cys Tyr Val Lys Met Val435 440 445Cys Leu Arg Glu Pro Pro Gln Leu Val Leu Gly Leu His Phe Leu Gly450 455 460Pro Asn Ala Gly Glu Val Thr Gln Gly Phe Ala Leu Gly Ile Lys Cys465 470 475 480Gly Ala Ser Tyr Ala Gln Val Met Arg Thr Val Gly Ile His Pro Thr485 490 495Cys Ser Glu Glu Val Val Lys Leu Arg Ile Ser Lys Arg Ser Gly Leu500 505 510Asp Pro Thr Val Thr Gly Cys Xaa Gly515 520210294211579212PRT213人220221VARIANT222578223Xaa＝任何胺基酸400294Ala Glu Arg Val Val Ile Phe Ser Lys Ser Tyr Cys Pro His Ser Thr1 5 10 15Arg Val Lys Glu Leu Phe Ser Ser Leu Gly Val Glu Cys Asn Val Leu20 25 30Glu Leu Asp Gln Val Asp Asp Gly Ala Arg Val Gln Glu Val Leu Ser35 40 45Glu Ile Thr Asn Gln Lys Thr Val Pro Asn Ile Phe Val Asn Lys Val50 55 60His Val Gly Gly Cys Asp Gln Thr Phe Gln Ala Tyr Gln Ser Gly Leu65 70 75 80Leu Gln Lys Leu Leu Gln Glu Asp Leu Ala Tyr Asp Tyr Asp Leu Ile85 90 95Ile Ile Gly Gly Gly Ser Gly Gly Leu Ser Cys Ala Lys Glu Ala Ala100 105 110Ile Leu Gly Lys Lys Val Met Val Leu Asp Phe Val Val Pro Ser Pro115 120 125Gln Gly Thr Ser Trp Gly Leu Gly Gly Thr Cys Val Asn Val Gly Cys130 135 140Ile Pro Lys Lys Leu Met His Gln Ala Ala Leu Leu Gly Gln Ala Leu145 150 155 160Cys Asp Ser Arg Lys Phe Gly Trp Glu Tyr Asn Gln Gln Val Arg His165 170 175Asn Trp Glu Thr Met Thr Lys Ala Ile Gln Asn His Ile Ser Ser Leu180 185 190Asn Trp Gly Tyr Arg Leu Ser Leu Arg Glu Lys Ala Val Ala Tyr Val195 200 205Ash Ser Tyr Gly Glu Phe Val Glu His His Lys Ile Lys Ala Thr Asn210 215 220Lys Lys Gly Gln Glu Thr Tyr Tyr Thr Ala Ala Gln Phe Val Ile Ala225 230 235 240Thr Gly Glu Arg Pro Arg Tyr Leu Gly Ile Gln Gly Asp Lys Glu Tyr245 250 255Cys Ile Thr Ser Asp Asp Leu Phe Ser Leu Pro Tyr Cys Pro Gly Lys260 265 270Thr Leu Val Val Gly Ala Ser Tyr Val Ala Leu Glu Cys Ala Gly Phe275 280 285Leu Ala Gly Phe Gly Leu Asp Val Thr Val Met Val Arg Ser Ile Leu290 295 300Leu Arg Gly Phe Asp Gln Glu Met Ala Glu Lys Val Gly Ser Tyr Met305 310 315 320Glu Gln His Gly Val Lys Phe Leu Arg Lys Phe Ile Pro Val Met Val325 330 335Gln Gln Leu Glu Lys Gly Ser Pro Gly Lys Leu Lys Val Leu Ala Lys340 345 350Ser Thr Glu Gly Thr Glu Thr Ile Glu Gly Val Tyr Asn Thr Val Leu355 360 365Leu Ala Ile Gly Arg Asp Ser Cys Thr Arg Lys Ile Gly Leu Glu Lys370 375 380Ile Gly Val Lys Ile Asn Glu Lys Ser Gly Lys Ile Pro Val Asn Asp385 390 395 400Val Glu Gln Thr Asn Val Pro Tyr Val Tyr Ala Val Gly Asp Ile Leu405 410 415Glu Asp Lys Pro Glu Leu Thr Pro Val Ala Ile Gln Ser Gly Lys Leu420 425 430Leu Ala Gln Arg Leu Phe Gly Ala Ser Leu Glu Lys Cys Asp Tyr Ile435 440 445Asn Val Pro Thr Thr Val Phe Thr Pro Leu Glu Tyr Gly Cys Cys Gly450 455 460Leu Ser Glu Glu Lys Ala Ile Glu Val Tyr Lys Lys Glu Asn Leu Glu465 470 475 480Ile Tyr His Thr Leu Phe Trp Pro Leu Glu Trp Thr Val Ala Gly Arg485 490 495Glu Asn Asn Thr Cys Tyr Ala Lys Ile Ile Cys Asn Lys Phe Asp His500 505 510Asp Arg Val Ile Gly Phe His Ile Leu Gly Pro Asn Ala Gly Glu Val515 520 525Thr Gln Gly Phe Ala Ala Ala Met Lys Cys Gly Leu Thr Lys Gln Leu530 535 540Leu Asp Asp Thr Ile Gly Ile His Pro Thr Cys Gly Glu Val Phe Thr545 550 555 560Thr Leu Glu Ile Thr Lys Ser Ser Gly Leu Asp Ile Thr Gln Lys Gly565 570 575Cys Xaa Gly210295211524212PRT213人220221VARIANT222523223Xaa＝任何胺基酸400295Met Ala Ala Met Ala Val Ala Leu Arg Gly Leu Gly Gly Arg Phe Arg1 5 10 15Trp Arg Thr Gln Ala Val Ala Gly Gly Val Arg Gly Ala Ala Arg Gly20 25 30Ala Ala Ala Gly Gln Arg Asp Tyr Asp Leu Leu Val Val Gly Gly Gly35 40 45Ser Gly Gly Leu Ala Cys Ala Lys Glu Ala Ala Gln Leu Gly Arg Lys50 55 60Val Ala Val Val Asp Tyr Val Glu Pro Ser Pro Gln Gly Thr Arg Trp65 70 75 80Gly Leu Gly Gly Thr Cys Val Asn Val Gly Cys Ile Pro Lys Lys Leu85 90 95Met His Gln Ala Ala Leu Leu Gly Gly Leu Ile Gln Asp Ala Pro Asn100 105 110Tyr Gly Trp Glu Val Ala Gln Pro Val Pro His Asp Trp Arg Lys Met115 120 125Ala Glu Ala Val Gln Asn His Val Lys Ser Leu Asn Trp Gly His Arg130 135 140Val Gln Leu Gln Asp Arg Lys Val Lys Tyr Phe Asn Ile Lys Ala Ser145 150 155 160Phe Val Asp Glu His Thr Val Cys Gly Val Ala Lys Gly Gly Lys Glu165 170 175Ile Leu Leu Ser Ala Asp His Ile Ile Ile Ala Thr Gly Gly Arg Pro180 185 190Arg Tyr Pro Thr His Ile Glu Gly Ala Leu Glu Tyr Gly Ile Thr Ser195 200 205Asp Asp Ile Phe Trp Leu Lys Glu Ser Pro Gly Lys Thr Leu Val Val210 215 220Gly Ala Ser Tyr Val Ala Leu Glu Cys Ala Gly Phe Leu Thr Gly Ile225 230 235 240Gly Leu Asp Thr Thr Ile Met Met Arg Ser Ile Pro Leu Arg Gly Phe245 250 255Asp Gln Gln Met Ser Ser Met Val Ile Glu His Met Ala Ser His Gly260 265 270Thr Arg Phe Leu Arg Gly Cys Ala Pro Ser Arg Val Arg Arg Leu Pro275 280 285Asp Gly Gln Leu Gln Val Thr Trp Glu Asp Ser Thr Thr Gly Lys Glu290 295 300Asp Thr Gly Thr Phe Asp Thr Val Leu Trp Ala Ile Gly Arg Val Pro305 310 315 320Asp Thr Arg Ser Leu Asn Leu Glu Lys Ala Gly Val Asp Thr Ser Pro325 330 335Asp Thr Gln Lys Ile Leu Val Asp Ser Arg Glu Ala Thr Ser Val Pro340 345 350His Ile Tyr Ala Ile Gly Asp Val Val Glu Gly Arg Pro Glu Leu Thr355 360 365Pro Ile Ala Ile Met Ala Gly Arg Leu Leu Val Gln Arg Leu Phe Gly370 375 380Gly Ser Ser Asp Leu Met Asp Tyr Asp Asn Val Pro Thr Thr Val Phe385 390 395 400Thr Pro Leu Glu Tyr Gly Cys Val Gly Leu Ser Glu Glu Glu Ala Val405 410 415Ala Arg His Gly Gln Glu His Val Glu Val Tyr His Ala His Tyr Lys420 425 430Pro Leu Glu Phe Thr Val Ala Gly Arg Asp Ala Ser Gln Cys Tyr Val435 440 445Lys Met Val Cys Leu Arg Glu Pro Pro Gln Leu Val Leu Gly Leu His450 455 460Phe Leu Gly Pro Asn Ala Gly Glu Val Thr Gln Gly Phe Ala Leu Gly465 470 475 480Ile Lys Cys Gly Ala Ser Tyr Ala Gln Val Met Arg Thr Val Gly Ile485 490 495His Pro Thr Cys Ser Glu Glu Val Val Lys Leu Arg Ile Ser Lys Arg500 505 510Ser Gly Leu Asp Pro Thr Val Thr Gly Cys Xaa Gly515 520210296211577212PAT213人220221VARIANT222576223Xaa＝任何胺基酸400296Arg Val Val Ile Phe Ser Lys Ser Tyr Cys Pro His Ser Thr Arg Val1 5 10 15Lys Glu Leu Phe Ser Ser Leu Gly Val Glu Cys Asn Val Leu Glu Leu20 25 30Asp Gln Val Asp Asp Gly Ala Arg Val Gln Glu Val Leu Ser Glu Ile35 40 45Thr Asn Gln Lys Thr Val Pro Asn Ile Phe Val Asn Lys Val His Val50 55 60Gly Gly Cys Asp Gln Thr Phe Gln Ala Tyr Gln Ser Gly Leu Leu Gln65 70 75 80Lys Leu Leu Gln Glu Asp Leu Ala Tyr Asp Tyr Asp Leu Ile Ile Ile85 90 95Gly Gly Gly Ser Gly Gly Leu Ser Cys Ala Lys Glu Ala Ala Ile Leu100 105 110Gly Lys Lys Val Met Val Leu Asp Phe Val Val Pro Ser Pro Gln Gly115 120 125Thr Ser Trp Gly Leu Gly Gly Thr Cys Val Asn Val Gly Cys Ile Pro130 135 140Lys Lys Leu Met His Gln Ala Ala Leu Leu Gly Gln Ala Leu Cys Asp145 150 155 160Ser Arg Lys Phe Gly Trp Glu Tyr Asn Gln Gln Val Arg His Asn Trp165 170 175Glu Thr Met Thr Lys Ala Ile Gln Asn His Ile Ser Ser Leu Asn Trp180 185 190Gly Tyr Arg Leu Ser Leu Arg Glu Lys Ala Val Ala Tyr Val Asn Ser195 200 205Tyr Gly Glu Phe Val Glu His His Lys Ile Lys Ala Thr Asn Lys Lys
210 215 220Gly Gln Glu Thr Tyr Tyr Thr Ala Ala Gln Phe Val Ile Ala Thr Gly225 230 235 240Glu Arg Pro Arg Tyr Leu Gly Ile Gln Gly Asp Lys Glu Tyr Cys Ile245 250 255Thr Ser Asp Asp Leu Phe Ser Leu Pro Tyr Cys Pro Gly Lys Pro Leu260 265 270Val Val Gly Ala Ser Tyr Val Ala Leu Glu Cys Ala Gly Phe Leu Ala275 280 285Gly Phe Gly Leu Asp Val Thr Val Met Val Arg Ser Ile Leu Leu Arg290 295 300Gly Phe Asp Gln Glu Met Ala Glu Lys Val Gly Ser Tyr Met Glu Gln305 310 315 320His Gly Val Lys Phe Leu Arg Lys Phe Ile Pro Val Met Val Gln Gln325 330 335Leu Glu Lys Gly Ser Pro Gly Lys Leu Lys Val Leu Ala Lys Ser Thr340 345 350Glu Gly Thr Glu Thr Ile Glu Gly Val Tyr Asn Thr Val Leu Leu Ala355 360 365Ile Gly Arg Asp Ser Cys Thr Arg Lys Ile Gly Leu Glu Lys Ile Gly370 375 380Val Lys Ile Asn Glu Lys Ser Gly Lys Ile Pro Val Asn Asp Val Glu385 390 395 400Gln Thr Asn Val Pro Tyr Val Tyr Ala Val Gly AsP Ile Leu Glu Asp405 410 415Lys Pro Glu Leu Thr Pro Val Ala Ile Gln Ser Gly Lys Leu Leu Ala420 425 430Gln Arg Leu Phe Gly Ala Ser Leu Glu Lys Cys Asp Tyr Ile Asn Val435 440 445Pro Thr Thr Val Phe Thr Pro Leu Glu Tyr Gly Cys Cys Gly Leu Ser450 455 460Glu Glu Lys Ala Ile Glu Val Tyr Lys Lys Glu Asn Leu Glu Ile Tyr465 470 475 480His Thr Leu Phe Trp Pro Leu Glu Trp Thr Val Ala Gly Arg Glu Asn485 490 495Asn Thr Cys Tyr Ala Lys Ile Ile Cys Asn Lys Phe Asp His Asp Arg500 505 510Val Ile Gly Phe His Ile Leu Gly Pro Asn Ala Gly Glu Val Thr Gln515 520 525Gly Phe Ala Ala Ala Met Lys Cys Gly Leu Thr Lys Gln Leu Leu Asp530 535 540Asp Thr Ile Gly Ile His Pro Thr Cys Gly Glu Val Phe Thr Thr Leu545 550 555 560Glu Ile Thr Lys Ser Ser Gly Leu Asp Ile Thr Gln Lys Gly Cys Xaa565 570 575Gly210297211494212PRT213人400297Met Glu Asp Gln Ala Gly Gln Arg Asp Tyr Asp Leu Leu Val Val Gly1 5 10 15Gly Gly Ser Gly Gly Leu Ala Cys Ala Lys Glu Ala Ala Gln Leu Gly20 25 30Arg Lys Val Ala Val Val Asp Tyr Val Glu Pro Ser Pro Gln Gly Thr35 40 45Arg Trp Gly Leu Gly Gly Thr Cys Val Asn Val Gly Cys Ile Pro Lys50 55 60Lys Leu Met His Gln Ala Ala Leu Leu Gly Gly Leu Ile Gln Asp Ala65 70 75 80Pro Asn Tyr Gly Trp Glu Val Ala Gln Pro Val Pro His Asp Trp Arg85 90 95Lys Met Ala Glu Ala Val Gln Asn His Val Lys Ser Leu Asn Trp Gly100 105 110His Arg Val Gln Leu Gln Asp Arg Lys Val Lys Tyr Phe Asn Ile Lys115 120 125Ala Ser Phe Val Asp Glu His Thr Val Cys Gly Val Ala Lys Gly Gly130 135 140Lys Glu Ile Leu Leu Ser Ala Asp His Ile Ile Ile Ala Thr Gly Gly145 150 155 160Arg Pro Arg Tyr Pro Thr His Ile Glu Gly Ala Leu Glu Tyr Gly Ile165 170 175Thr Ser Asp Asp Ile Phe Trp Leu Lys Glu Ser Pro Gly Lys Thr Leu180 185 190Val Val Gly Ala Ser Tyr Val Ala Leu Glu Cys Ala Gly Phe Leu Thr195 200 205Gly Ile Gly Leu Asp Thr Thr Ile Met Met Arg Ser Ile Pro Leu Arg210 215 220Gly Phe Asp Gln Gln Met Ser Ser Met Val Ile Glu His Met Ala Ser225 230 235 240His Gly Thr Arg Phe Leu Arg Gly Cys Ala Pro Ser Arg Val Arg Arg245 250 255Leu Pro Asp Gly Gln Leu Gln Val Thr Trp Glu Asp Ser Thr Thr Gly260 265 270Lys Glu Asp Thr Gly Thr Phe Asp Thr Val Leu Trp Ala Ile Gly Arg275 280 285Val Pro Asp Thr Arg Ser Leu Asn Leu Glu Lys Ala Gly Val Asp Thr290 295 300Ser Pro Asp Thr Gln Lys Ile Leu Val Asp Ser Arg Glu Ala Thr Ser305 310 315 320Val Pro His Ile Tyr Ala Ile Gly Asp Val Val Glu Gly Arg Pro Glu325 330 335Leu Thr Pro Thr Ala Ile Met Ala Gly Arg Leu Leu Val Gln Arg Leu340 345 350Phe Gly Gly Ser Ser Asp Leu Met Asp Tyr Asp Asn Val Pro Thr Thr355 360 365Val Phe Thr Pro Leu Glu Tyr Gly Cys Val Gly Leu Ser Glu Glu Glu370 375 380Ala Val Ala Arg His Gly Gln Glu His Val Glu Val Tyr His Ala His385 390 395 400Tyr Lys Pro Leu Glu Phe Thr Val Ala Gly Arg Asp Ala Ser Gln Cys405 410 415Tyr Val Lys Met Val Cys Leu Arg Glu Pro Pro Gln Leu Val Leu Gly420 425 430Leu His Phe Leu Gly Pro Asn Ala Gly Glu Val Thr Gln Gly Phe Ala435 440 445Leu Gly Ile Lys Cys Gly Ala Ser Tyr Ala Gln Val Met Arg Thr Val450 455 460Gly Ile His Pro Thr Cys Ser Glu Glu Val Val Lys Leu Arg Ile Ser465 470 475 480Lys Arg Ser Gly Leu Asp Pro Thr Val Thr Gly Cys Cys Gly485 490210298211521212PRT213人400298Met Ala Ala Met Ala Val Ala Leu Arg Gly Leu Gly Gly Arg Phe Arg1 5 10 15Trp Arg Thr Gln Ala Val Ala Gly Gly Val Arg Gly Ala Ala Arg Gly20 25 30Ala Ala Gly Gln Arg Asp Tyr Asp Leu Leu Val Val Gly Gly Gly Ser35 40 45Gly Gly Leu Ala Cys Ala Lys Glu Ala Ala Gln Leu Gly Arg Lys Val50 55 60Ser Val Val Asp Tyr Val Glu Pro Ser Pro Gln Gly Thr Arg Trp Gly65 70 75 80Leu Gly Gly Thr Cys Val Asn Val Gly Cys Ile Pro Lys Lys Leu Met85 90 95His Gln Ala Ala Leu Leu Gly Gly Leu Ile Gln Asp Ala Pro Asn Tyr100 105 110Gly Trp Glu Val Ala Gln Pro Val Pro His Asp Trp Arg Lys Met Ala115 120 125Glu Ala Val Gln Asn His Val Lys Ser Leu Asn Trp Gly His Arg Val130 135 140Gln Leu Gln Asp Arg Lys Val Lys Tyr Phe Asn Ile Lys Ala Ser Phe145 150 155 160Val Asp Glu His Thr Val Cys Gly Val Ala Lys Gly Gly Lys Glu Ile165 170 175Leu Leu Ser Ala Asp His Ile Ile Ile Ala Thr Gly Gly Arg Pro Arg180 185 190Tyr Pro Thr His Ile Glu Gly Ala Leu Glu Tyr Gly Ile Thr Ser Asp195 200 205Asp Ile Phe Trp Leu Lys Glu Ser Pro Gly Lys Thr Leu Val Val Gly210 215 220Ala Ser Tyr Val Ala Leu Glu Cys Ala Gly Phe Leu Thr Gly Ile Gly225 230 235 240Leu Asp Thr Thr Ile Met Met Arg Ser Ile Pro Leu Arg Gly Phe Asp245 250 255Gln Gln Met Ser Ser Met Val Ile Glu His Met Ala Ser His Gly Thr260 265 270Arg Phe Leu Arg Gly Cys Ala Pro Ser Arg Val Lys Arg Leu Pro Asp275 280 285Gly Gln Leu Gln Val Thr Trp Glu Asp Ser Thr Thr Gly Lys Glu Asp290 295 300Thr Gly Thr Phe Asp Thr Val Leu Trp Ala Ile Gly Arg Val Pro Asp305 310 315 320Thr Arg Ser Leu Asn Leu Glu Lys Ala Gly Val Asp Thr Ser Pro Asp325 330 335Thr Gln Lys Ile Leu Val Asp Ser Arg Glu Ala Thr Ser Val Pro His340 345 350Ile Tyr Ala Ile Gly Asp Val Val Glu Gly Arg Pro Glu Leu Thr Pro355 360 365Thr Ala Ile Met Ala Gly Arg Leu Leu Val Gln Arg Leu Phe Gly Gly370 375 380Ser Ser Asp Leu Met Asp Tyr Asp Asn Val Pro Thr Thr Val Phe Thr385 390 395 400Pro Leu Glu Tyr Gly Cys Val Gly Leu Ser Glu Glu Glu Ala Val Ala405 410 415Arg His Gly Gln Glu His Val Glu Val Tyr His Ala His Tyr Lys Pro420 425 430Leu Glu Phe Thr Val Ala Gly Arg Asp Ala Ser Gln Cys Tyr Val Lys435 440 445Met Val Cys Leu Arg Glu Pro Pro Gln Leu Val Leu Gly Leu His Phe450 455 460Leu Gly Pro Asn Ala Gly Glu Val Thr Gln Gly Phe Ala Leu Gly Ile465 470 475 480Lys Cys Gly Ala Ser Tyr Ala Gln Val Met Arg Thr Val Gly Ile His485 490 495Pro Thr Cys Ser Glu Glu Val Val Lys Leu Arg Ile Ser Lys Arg Ser500 505 510Gly Leu Asp Pro Thr Val Thr Gly Cys515 520210299211549212PRT213人400299Met Ser Cys Glu Asp Gly Arg Ala Leu Glu Gly Thr Leu Ser Glu Leu1 5 10 15Ala Ala Glu Thr Asp Leu Pro Val Val Phe Val Lys Gln Arg Lys Ile20 25 30Gly Gly His Gly Pro Thr Leu Lys Ala Tyr Gln Glu Gly Arg Leu Gln35 40 45Lys Leu Leu Lys Met Asn Gly Pro Glu Asp Leu Pro Lys Ser Tyr Asp50 55 60Tyr Asp Leu Ile Ile Ile Gly Gly Gly Ser Gly Gly Leu Ala Ala Ala65 70 75 80Lys Glu Ala Ala Gln Tyr Gly Lys Lys Val Met Val Leu Asp Phe Val85 90 95Thr Pro Thr Pro Leu Gly Thr Arg Trp Gly Leu Gly Gly Thr Cys Val100 105 110Asn Val Gly Cys Ile Pro Lys Lys Leu Met His Gln Ala Ala Leu Leu115 120 125Gly Gln Ala Leu Gln Asp Ser Arg Ash Tyr Gly Trp Lys Val Glu Glu130 135 140Thr Val Lys His Asp Trp Asp Arg Met Ile Glu Ala Val Gln Asn His145 150 155 160Ile Gly Ser Leu Asn Trp Gly Tyr Arg Val Ala Leu Arg Glu Lys Lys165 170 175Val Val Tyr Glu Asn Ala Tyr Gly Gln Phe Ile Gly Pro His Arg Ile180 185 190Lys Ala Thr Asn Asn Lys Gly Lys Glu Lys Ile Tyr Ser Ala Glu Arg195 200 205Phe Leu Ile Ala Thr Gly Glu Arg Pro Arg Tyr Leu Gly Ile Pro Gly210 215 220Asp Lys Glu Tyr Cys Ile Ser Ser Asp Asp Leu Phe Ser Leu Pro Tyr225 230 235 240Cys Pro Gly Lys Thr Leu Val Val Gly Ala Ser Tyr Val Ala Leu Glu245 250 255Cys Ala Gly Phe Leu Ala Gly Ile Gly Leu Asp Val Thr Val Met Val260 265 270Arg Ser Ile Leu Leu Arg Gly Phe Asp Gln Asp Met Ala Asn Lys Ile275 280 285Gly Glu His Met Glu Glu His Gly Ile Lys Phe Ile Arg Gln Phe Val290 295 300Pro Ile Lys Val Glu Gln Ile Glu Ala Gly Thr Pro Gly Arg Leu Arg305 310 315 320Val Val Ala Gln Ser Thr Asn Ser Glu Glu Ile Ile Glu Gly Glu Tyr325 330 335Asn Thr Val Met Leu Ala Ile Gly Arg Asp Ala Cys Thr Arg Lys Ile340 345 350Gly Leu Glu Thr Val Gly Val Lys Ile Asn Glu Lys Thr Gly Lys Ile355 360 365Pro Val Thr Asp Glu Glu Gln Thr Asn Val Pro Tyr Ile Tyr Ala Ile370 375 380Gly Asp Ile Leu Glu Asp Lys Val Glu Leu Thr Pro Val Ala Ile Gln385 390 395 400Ala Gly Arg Leu Leu Ala Gln Arg Leu Tyr Ala Gly Ser Thr Val Lys405 410 415Cys Asp Tyr Glu Asn Val Pro Thr Thr Val Phe Thr Pro Leu Glu Tyr420 425 430Gly Ala Cys Gly Leu Ser Glu Glu Lys Ala Val Glu Lys Phe Gly Glu435 440 445Glu Asn Ile Glu Val Tyr His Ser Tyr Phe Trp Pro Leu Glu Trp Thr450 455 460Ile Pro Ser Arg Asp Asn Asn Lys Cys Tyr Ala Lys Ile Ile Cys Asn465 470 475 480Thr Lys Asp Asn Glu Arg Val Val Gly Phe His Val Leu Gly Pro Asn485 490 495Ala Gly Glu Val Thr Gln Gly Phe Ala Ala Ala Leu Lys Cys Gly Leu500 505 510Thr Lys Lys Gln Leu Asp Ser Thr Ile Gly Ile His Pro Val Cys Ala515 520 525Glu Val Phe Thr Thr Leu Ser Val Thr Lys Arg Ser Gly Ala Ser Ile530 535 540Leu Gln Ala Gly Cys545210300211613212PRT213臺灣鼷鼠220221VARIANT222612223Xaa＝任何胺基酸400300Met Pro Val Asp Asp Cys Trp Leu Tyr Phe Pro Ala Ser Arg Gly Arg1 5 10 15Thr Phe Val Gln Thr Val Trp Val Ala Pro Thr Cys Pro Asn Cys Cys20 25 30Trp Phe Pro Gly Phe Leu Pro Pro Val Pro Arg Pro Pro His Val Pro35 40 45Arg Val Leu Leu Arg Gly Pro Arg Gly Ala Val Leu Pro Ala Ser Arg50 55 60Pro Ser Lys Thr Leu Pro Ser Ser Ser Gln Thr Pro Cys Pro Thr Asp65 70 75 80Pro Cys Ile Cys Pro Pro Pro Ser Thr Pro Asp Ser Arg Gln Glu Lys85 90 95Asn Thr Gln Ser Glu Leu Pro Asn Lys Lys Gly Gln Leu Gln Lys Leu100 105 110Pro Thr Met Asn Gly Ser Lys Asp Pro Pro Gly Ser Tyr Asp Phe Asp115 120 125Leu Ile Ile Ile Gly Gly Gly Ser Gly Gly Leu Ala Ala Ala Lys Glu130 135 140Ala Ala Lys Phe Asp Lys Lys Val Leu Val Leu Asp Phe Val Thr Pro145 150 155 160Thr Pro Leu Gly Thr Arg Trp Gly Leu Gly Gly Thr Cys Val Asn Val165 170 175Gly Cys Ile Pro Lys Lys Leu Met His Gln Ala Ala Leu Leu Gly Gln180 185 190Ala Leu Lys Asp Ser Arg Asn Tyr Gly Trp Lys Val Glu Asp Thr Val195 200 205Lys His Asp Trp Glu Lys Met Thr Glu Ser Val Gln Ser His Ile Gly210 215 220Ser Leu Asn Trp Gly Tyr Arg Val Ala Leu Arg Glu Lys Lys Val Val225 230 235 240Tyr Glu Asn Ala Tyr Gly Arg Phe Ile Gly Pro His Arg Ile Val Ala245 250 255Thr Asn Asn Lys Gly Lys Glu Lys Ile Tyr Ser Ala Glu Arg Phe Leu260 265 270Ile Ala Thr Gly Glu Arg Pro Arg Tyr Leu Gly Ile Pro Gly Asp Lys275 280 285Glu Tyr Cys Ile Ser Ser Asp Asp Leu Phe Ser Leu Pro Tyr Cys Pro290 295 300Gly Lys Thr Leu Val Val Gly Ala Ser Tyr Val Ala Leu Glu Cys Ala305 310 315 320Gly Phe Leu Ala Gly Ile Gly Leu Asp Val Thr Val Met Val Arg Ser325 330 335Ile Leu Leu Arg Gly Phe Asp Gln Asp Met Ala Asn Lys Ile Gly Glu340 345 350His Met Glu Glu His Gly Ile Lys Phe Ile Arg Gln Phe Val Pro Thr355 360 365Lys Ile Glu Gln Ile Glu Ala Gly Thr Pro Gly Arg Leu Arg Val Thr370 375 380Ala Gln Ser Thr Asn Ser Glu Glu Thr Ile Glu Gly Glu Phe Ash Thr385 390 395 400Val Leu Leu Ala Val Gly Arg Asp Ser Cys Thr Arg Thr Ile Gly Leu405 410 415Glu Thr Val Gly Val Lys Ile Asn Glu Lys Thr Gly Lys Ile Pro Val
420 425 430Thr Asp Glu Glu Gln Thr Asn Val Pro Tyr Ile Tyr Ala Ile Gly Asp435 440 445Ile Leu Glu Gly Lys Leu Glu Leu Thr Pro Val Ala Ile Gln Ala Gly450 455 460Arg Leu Leu Ala Gln Arg Leu Tyr Gly Gly Ser Asn Val Lys Cys Asp465 470475 480Tyr Asp Asn Val Pro Thr Thr Val Phe Thr Pro Leu Glu Tyr Gly Cys485 490 495Cys Gly Leu Ser Glu Glu Lys Ala Val Glu Lys Phe Gly Glu Glu Asn500 505 510Ile Glu Val Tyr His Ser Phe Phe Trp Pro Leu Glu Trp Thr Val Pro515 520 525Ser Arg Asp Asn Asn Lys Cys Tyr Ala Lys Ile Ile Cys Asn Leu Lys530 535 540Asp Asp Glu Arg Val Val Gly Phe His Val Leu Gly Pro Asn Ala Gly545 550 555 560Glu Val Thr Gln Gly Phe Ala Ala Ala Leu Lys Cys Gly Leu Thr Lys565 570 575Gln Gln Leu Asp Ser Thr Ile Gly Ile His Pro Val Cys Ala Glu Ile580 585 590Phe Thr Thr Leu Ser Val Thr Lys Arg Ser Gly Gly Asp Ile Leu Gln595 600 605Ser Gly Cys Xaa Gly610210301211310212PRT213臺灣鼷鼠400301Met Asn Gly Ser Lys Asp Pro Pro Gly Ser Tyr Asp Phe Asp Leu Ile1 5 10 15Ile Ile Gly Gly Gly Ser Gly Gly Leu Ala Ala Ala Lys Glu Ala Ala20 25 30Lys Phe Asp Lys Lys Val Leu Val Leu Asp Phe Val Thr Pro Thr Pro35 40 45Leu Gly Thr Arg Trp Gly Leu Gly Gly Thr Cys Val Asn Val Gly Cys50 55 60Ile Pro Lys Lys Leu Met His Gln Ala Ala Leu Leu Gly Gln Ala Leu65 70 75 80Lys Asp Ser Arg Asn Tyr Gly Trp Lys Val Glu Asp Thr Val Lys His85 90 95Asp Trp Glu Lys Met Thr Glu Ser Val Gln Ser His Ile Gly Ser Leu100 105 110Asn Trp Gly Tyr Arg Val Ala Leu Arg Glu Lys Lys Val Val Tyr Glu115 120 125Asn Ala Tyr Gly Arg Phe Ile Gly Pro His Arg Ile Val Ala Thr Asn130 135 140Asn Lys Gly Lys Glu Lys Ile Tyr Ser Ala Glu Arg Phe Leu Ile Ala145 150 155 160Thr Gly Glu Arg Pro Arg Tyr Leu Gly Ile Pro Gly Asp Lys Glu Tyr165 170 175Cys Ile Ser Ser Asp Asp Leu Phe Ser Leu Pro Tyr Cys Pro Gly Lys180 185 190Thr Leu Val Val Gly Ala Ser Tyr Val Ala Leu Glu Cys Ala Gly Phe195 200 205Leu Ala Gly Ile Gly Leu Asp Val Thr Val Met Val Arg Ser Ile Leu210 215 220Leu Arg Gly Phe Asp Gln Asp Met Ala Asn Lys Ile Gly Glu His Met225 230 235 240Glu Glu His Gly Ile Lys Phe Ile Arg Gln Phe Val Pro Thr Lys Ile245 250 255Glu Gln Ile Glu Ala Gly Thr Pro Gly Arg Leu Arg Val Thr Ala Gln260 265 270Ser Thr Asn Ser Glu Glu Thr Ile Glu Gly Glu Phe Asn Thr Val Leu275 280 285Leu Ala Val Gly Arg Asp Ser Cys Thr Arg Thr Ile Gly Leu Glu Thr290 295 300Val Gly Val Lys Ile Asn305 310210302211613212PRT213臺灣鼷鼠400302Met Ser Ser Pro Pro Gly Arg Arg Ala Arg Leu Ala Ser Pro Gly Thr1 5 10 15Ser Arg Pro Ser Ser Glu Ala Arg Glu Glu Leu Arg Arg Arg Leu Arg20 25 30Asp Leu Ile Glu Gly Asn Arg Val Met Ile Phe Ser Lys Ser Tyr Cys35 40 45Pro His Ser Thr Arg Val Lys Glu Leu Phe Ser Ser Leu Gly Val Val50 55 60Tyr Asn Ile Leu Glu Leu Asp Gln Val Asp Asp Gly Ala Ser Val Gln65 70 75 80Glu Val Leu Thr Glu Ile Ser Asn Gln Lys Thr Val Pro Asn Ile Phe85 90 95Val Asn Lys Val His Val Gly Gly Cys Asp Arg Thr Phe Gln Ala His100 105 110Gln Asn Gly Leu Leu Gln Lys Leu Leu Gln Asp Asp Ser Ala His Asp115 120 125Tyr Asp Leu Ile Ile Ile Gly Gly Gly Ser Gly Gly Leu Ser Cys Ala130 135 140Lys Glu Ala Ala Asn Leu Gly Lys Lys Val Met Val Leu Asp Phe Val145 150 155 160Val Pro Ser Pro Gln Gly Thr Thr Trp Gly Leu Gly Gly Thr Cys Val165 170 175Asn Val Gly Cys Ile Pro Lys Lys Leu Met His Gln Ala Ala Leu Leu180 185 190Gly His Ala Leu Gln Asp Ala Lys Lys Tyr Gly Trp Glu Tyr Asn Gln195 200 205Gln Val Lys His Asn Trp Glu Ala Met Thr Glu Ala Ile Gln Ser His210 215 220Ile Gly Ser Leu Asn Trp Gly Tyr Arg Val Thr Leu Arg Glu Lys Gly225 230 235 240Val Thr Tyr Val Asn Ser Phe Gly Glu Phe Val Asp Leu His Lys Ile245 250 255Lys Ala Thr Asn Lys Lys Gly Gln Glu Thr Phe Tyr Thr Ala Ser Lys260 265 270Phe Val Ile Ala Thr Gly Glu Arg Pro Arg Tyr Leu Gly Ile Gln Gly275 280 285Asp Lys Glu Tyr Cys Ile Thr Ser Asp Asp Leu Phe Ser Leu Pro Tyr290 295 300Cys Pro Gly Cys Thr Leu Val Val Gly Ala Ser Tyr Val Gly Leu Glu305 310 315 320Cys Ala Gly Phe Leu Ala Gly Leu Gly Leu Asp Val Thr Val Met Val325 330 335Arg Ser Val Leu Leu Arg Gly Phe Asp Gln Glu Met Ala Glu Lys Val340 345 350Gly Ser Tyr Leu Glu Gln Gln Gly Val Lys Phe Gln Arg Lys Phe Thr355 360 365Pro Ile Leu Val Gln Gln Leu Glu Lys Gly Leu Pro Gly Lys Leu Lys370 375 380Val Val Ala Lys Ser Thr Glu Gly Pro Glu Thr Val Glu Gly Ile Tyr385 390 395 400Asn Thr Val Leu Leu Ala Ile Gly Arg Asp Ser Cys Thr Arg Lys Ile405 410 415Gly Leu Glu Lys Ile Gly Val Lys Ile Asn Glu Lys Asn Gly Lys Ile
420 425 430Pro Val Asn Asp Val Glu Gln Thr Asn Val Pro His Val Tyr Ala Ile435 440 445Gly Asp Ile Leu Asp Gly Lys Pro Glu Leu Thr Pro Val Ala Ile Gln450 455 460Ala Gly Lys Leu Leu Ala Arg Arg Leu Phe Gly Val Ser Leu Glu Lys465 470 475 480Cys Asp Tyr Ile Asn Ile Pro Thr Thr Val Phe Thr Pro Leu Glu Tyr485 490 495Gly Cys Cys Gly Leu Ser Glu Glu Lys Ala Ile Glu Met Tyr Lys Lys500 505 510Glu Asn Leu Glu Val Tyr His Thr Leu Phe Trp Pro Leu Glu Trp Thr515 520 525Val Ala Gly Arg Asp Asn Asn Thr Cys Tyr Ala Lys Ile Ile Cys Asn530 535 540Lys Phe Asp Asn Glu Arg Val Val Gly Phe His Leu Leu Gly Pro Asn545 550 555 560Ala Gly Glu Ile Thr Gln Gly Phe Ala Ala Ala Met Lys Cys Gly Leu565 570 575Thr Lys Gln Leu Leu Asp Asp Thr Ile Gly Ile His Pro Thr Cys Gly580 585 590Glu Val Phe Thr Thr Leu Glu Ile Thr Lys Ser Ser Gly Leu Asp Ile595 600 605Thr Gln Lys Gly Cys61021030321l524212PRT213臺灣鼷鼠220221VARIANT222523223Xaa＝任何胺基酸400303Met Val Ala Ala Met Val Ala Ala Leu Arg Gly Pro Ser Arg Arg Phe1 5 10 15Arg Pro Arg Thr Arg Ala Leu Thr Arg Gly Thr Arg Gly Ala Ala Ser20 25 30Ala Ala Gly Gly Gln Gln Ser Phe Asp Leu Leu Val Ile Gly Gly Gly35 40 45Ser Gly Gly Leu Ala Cys Ala Lys Glu Ala Ala Gln Leu Gly Lys Lys50 55 60Val Ala Val Ala Asp Tyr Val Glu Pro Ser Pro Arg Gly Thr Lys Trp65 70 75 80Gly Leu Gly Gly Thr Cys Val Asn Val Gly Cys Ile Pro Lys Lys Leu85 90 95Met His Gln Ala Ala Leu Leu Gly Gly Met Ile Arg Asp Ala His His100 105 110Tyr Gly Trp Glu Val Ala Gln Pro Val Gln His Asn Trp Lys Thr Met115 120 125Ala Glu Ala Val Gln Asn His Val Lys Ser Leu Asn Trp Gly His Arg130 135 140Val Gln Leu Gln Asp Arg Lys Val Lys Tyr Phe Asn Ile Lys Ala Ser145 150 155 160Phe Val Asp Glu His Thr Val Arg Gly Val Asp Lys Gly Gly Lys Ala165 170 175Thr Leu Leu Ser Ala Glu His Ile Val Ile Ala Thr Gly Gly Arg Pro180 185 190Arg Tyr Pro Thr Gln Val Lys Gly Ala Leu Glu Tyr Gly Ile Thr Ser195 200 205Asp Asp Ile Phe Trp Leu Lys Glu Ser Pro Gly Lys Thr Leu Val Val210 215 220Gly Ala Ser Tyr Val Ala Leu Glu Cys Ala Gly Phe Leu Thr Gly Ile225 230 235 240Gly Leu Asp Thr Thr Val Met Met Arg Ser Ile Pro Leu Arg Gly Phe245 250 255Asp Gln Gln Met Ser Ser Leu Val Thr Glu His Met Glu Ser His Gly260 265 270Thr Gln Phe Leu Lys Gly Cys Val Pro Ser His Ile Lys Lys Leu Pro275 280 285Thr Asn Gln Leu Gln Val Thr Trp Glu Asp His Ala Ser Gly Lys Glu290 295 300Asp Thr Gly Thr Phe Asp Thr Val Leu Trp Ala Ile Gly Arg Val Pro305 310 315 320Glu Thr Arg Thr Leu Asn Leu Glu Lys Ala Gly Ile Ser Thr Asn Pro325 330 335Lys Asn Gln Lys Ile Ile Val Asp Ala Gln Glu Ala Thr Ser Val Pro340 345 350His Ile Tyr Ala Ile Gly Asp Val Ala Glu Gly Arg Pro Glu Leu Thr355 360 365Pro Thr Ala Ile Lys Ala Gly Lys Leu Leu Ala Gln Arg Leu Phe Gly370 375 380Lys Ser Ser Thr Leu Met Asp Tyr Ser Asn Val Pro Thr Thr Val Phe385 390 395 400Thr Pro Leu Glu Tyr Gly Cys Val Gly Leu Ser Glu Glu Glu Ala Val405 410 415Ala Leu His Gly Gln Glu His Val Glu Val Tyr His Ala Tyr Tyr Lys420 425 430Pro Leu Glu Phe Thr Val Ala Asp Arg Asp Ala Ser Gln Cys Tyr Ile435 440 445Lys Met Val Cys Met Arg Glu Pro Pro Gln Leu Val Leu Gly Leu His450 455 460Phe Leu Gly Pro Asn Ala Gly Glu Val Thr Gln Gly Phe Ala Leu Gly465 470 475 480Ile Lys Cys Gly Ala Ser Tyr Ala Gln Val Met Gln Thr Val Gly Ile485 490 495His Pro Thr Cys Ser Glu Glu Val Val Lys Leu His Ile Ser Lys Arg500 505 510Ser Gly Leu Glu Pro Thr Val Thr Gly Cys Xaa Gly515 520210304211528212PRT213臺灣鼷鼠220221VARIANT222527223Xaa＝任何胺基酸400304Met Ala Ala Met Val Ala Gly Arg Met Trp Ala Ala Leu Arg Gly Pro1 5 10 15Ser Arg Arg Phe Arg Pro Arg Thr Arg Ala Leu Thr Arg Gly Thr Arg20 25 30Gly Ala Ala Ser Ala Ala Gly Gly Gln Gln Ser Phe Asp Leu Leu Val35 40 45Ile Gly Gly Gly Ser Gly Gly Leu Ala Cys Ala Lys Glu Ala Ala Gln50 55 60Leu Gly Lys Lys Val Ala Val Ala Asp Tyr Val Glu Pro Ser Pro Arg65 70 75 80Gly Thr Lys Trp Gly Leu Gly Gly Thr Cys Val Asn Val Gly Cys Ile85 90 95Pro Lys Lys Leu Met His Gln Ala Ala Leu Leu Gly Gly Met Ile Arg100 105 110Asp Ala His His Tyr Gly Trp Glu Val Ala Gln Pro Val Gln His Asn115 120 125Trp Lys Thr Met Ala Glu Ala Val Gln Asn His Val Lys Ser Leu Asn
130 135140Trp Gly His Arg Val Gln Leu Gln Asp Arg Lys Val Lys Tyr Phe Asn145 150 155 160Ile Lys Ala Ser Phe Val Asp Glu His Thr Val Arg Gly Val Asp Lys165 170 175Gly Gly Lys Ala Thr Leu Leu Ser Ala Glu His Ile Val Ile Ala Thr180 185 190Gly Gly Arg Pro Arg Tyr Pro Thr Gln Val Lys Gly Ala Leu Glu Tyr195 200 205Gly Ile Thr Ser Asp Asp Ile Phe Trp Leu Lys Glu Ser Pro Gly Lys210 215 220Thr Leu Val Val Gly Ala Ser Tyr Val Ala Leu Glu Cys Ala Gly Phe225 230 235 240Leu Thr Gly Ile Gly Leu Asp Thr Thr Val Met Met Arg Ser Ile Pro245 250 255Leu Arg Gly Phe Asp Gln Gln Met Ser Ser Leu Val Thr Glu His Met260 265 270Glu Ser His Gly Thr Gln Phe Leu Lys Gly Cys Val Pro Ser His Ile275 280 285Lys Lys Leu Pro Thr Asn Gln Leu Gln Val Thr Trp Glu Asp His Ala290 295 300Ser Gly Lys Glu Asp Thr Gly Thr Phe Asp Thr Val Leu Trp Ala Ile305 310 315 320Gly Arg Val Pro Glu Thr Arg Thr Leu Asn Leu Glu Lys Ala Gly Ile325 330 335Ser Thr Asn Pro Lys Asn Gln Lys Ile Ile Val Asp Ala Gln Glu Ala340 345 350Thr Ser Val Pro His Ile Tyr Ala Ile Gly Asp Val Ala Glu Gly Arg355 360 365Pro Glu Leu Thr Pro Thr Ala Ile Lys Ala Gly Lys Leu Leu Ala Gln370 375 380Arg Leu Phe Gly Lys Ser Ser Thr Leu Met Asp Tyr Ser Asn Val Pro385 390 395 400Thr Thr Val Phe Thr Pro Leu Glu Tyr Gly Cys Val Gly Leu Ser Glu405 410 415Glu Glu Ala Val Ala Leu His Gly Gln Glu His Val Glu Val Tyr His420 425 430Ala Tyr Tyr Lys Pro Leu Glu Phe Thr Val Ala Asp Arg Asp Ala Ser435 440 445Gln Cys Tyr Ile Lys Met Val Cys Met Arg Glu Pro Pro Gln Leu Val450 455 460Leu Gly Leu His Phe Leu Gly Pro Asn Ala Gly Glu Val Thr Gln Gly465 470 475 480Phe Ala Leu Gly Ile Lys Cys Gly Ala Ser Tyr Ala Gln Val Met Gln485 490 495Thr Val Gly Ile His Pro Thr Cys Ser Glu Glu Val Val Lys Leu His500 505 510Ile Ser Lys Arg Ser Gly Leu Glu Pro Thr Val Thr Gly Cys Xaa Gly515 520 525210305211520212PRT213臺灣鼷鼠400305Met Val Ala Ala Leu Arg Gly Pro Ser Arg Arg Phe Arg Pro Arg Thr1 5 10 15Arg Ala Leu Thr Arg Gly Thr Arg Gly Ala Ala Ser Ala Ala Gly Gly20 25 30Gln Gln Ser Phe Asp Leu Leu Val Ile Gly Gly Gly Ser Gly Gly Leu35 40 45Ala Cys Ala Lys Glu Ala Ala Gln Leu Gly Lys Lys Val Ala Val Ala50 55 60Asp Tyr Val Glu Pro Ser Pro Arg Gly Thr Lys Trp Gly Leu Gly Gly65 70 75 80Thr Cys Val Asn Val Gly Cys Ile Pro Lys Lys Leu Met His Gln Ala85 90 95Ala Leu Leu Gly Gly Met Ile Arg Asp Ala His His Tyr Gly Trp Glu100 105 110Val Ala Gln Pro Val Gln His Asn Trp Lys Thr Met Ala Glu Ala Val115 120 125Gln Asn His Val Lys Ser Leu Asn Trp Gly His Arg Val Gln Leu Gln130 135 140Asp Arg Lys Val Lys Tyr Phe Asn Ile Lys Ala Ser Phe Val Asp Glu145 150 155 160His Thr Val Arg Gly Val Asp Lys Gly Gly Lys Ala Thr Leu Leu Ser165 170 175Ala Glu His Ile Val Ile Ala Thr Gly Gly Arg Pro Arg Tyr Pro Thr180 185 190Gln Val Lys Gly Ala Leu Glu Tyr Gly Ile Thr Ser Asp Asp Ile Phe195 200 205Trp Leu Lys Glu Ser Pro Gly Lys Thr Leu Val Val Gly Ala Ser Tyr210 215 220Val Ala Leu Glu Cys Ala Gly Phe Leu Thr Gly Ile Gly Leu Asp Thr225 230 235 240Thr Val Met Met Arg Ser Ile Pro Leu Arg Gly Phe Asp Gln Gln Met245 250 255Ser Ser Leu Val Thr Glu His Met Glu Ser His Gly Thr Gln Phe Leu260 265 270Lys Gly Cys Val Pro Ser His Ile Lys Lys Leu Pro Thr Asn Gln Leu275 280 285Gln Val Thr Trp Glu Asp His Ala Ser Gly Lys Glu Asp Thr Gly Thr290 295 300Phe Asp Thr Val Leu Trp Ala Ile Gly Arg Val Pro Glu Thr Arg Thr305 310 315 320Leu Asn Leu Glu Lys Ala Gly Ile Ser Thr Asn Pro Lys Asn Gln Lys325 330 335Ile Ile Val Asp Ala Gln Glu Ala Thr Ser Val Pro His Ile Tyr Ala340 345 350Ile Gly Asp Val Ala Glu Gly Arg Pro Glu Leu Thr Pro Thr Ala Ile355 360 365Lys Ala Gly Lys Leu Leu Ala Gln Arg Leu Phe Gly Lys Ser Ser Thr370 375 380Leu Met Asp Tyr Ser Asn Val Pro Thr Thr Val Phe Thr Pro Leu Glu385 390 395 400Tyr Gly Cys Val Gly Leu Ser Glu Glu Glu Ala Val Ala Leu His Gly405 410 415Gln Glu His Val Glu Val Tyr His Ala Tyr Tyr Lys Pro Leu Glu Phe420 425 430Thr Val Ala Asp Arg Asp Ala Ser Gln Cys Tyr Ile Lys Met Val Cys435 440 445Met Arg Glu Pro Pro Gln Leu Val Leu Gly Leu His Phe Leu Gly Pro450 455 460Asn Ala Gly Glu Val Thr Gln Gly Phe Ala Leu Gly Ile Lys Cys Gly465 470 475 480Ala Ser Tyr Ala Gln Val Met Gln Thr Val Gly Ile His Pro Thr Cys485 490 495Ser Glu Glu Val Val Lys Leu His Ile Ser Lys Arg Ser Gly Leu Glu500 505 510Pro Thr Val Thr Gly Cys Cys Gly515 520210306211499212PRT213臺灣鼷鼠400306Met Asn Gly Ser Lys Asp Pro Pro Gly Ser Tyr Asp Phe Asp Leu Ile1 5 10 15Ile Ile Gly Gly Gly Ser Gly Gly Leu Ala Ala Ala Lys Glu Ala Ala
20 25 30Lys Phe Asp Lys Lys Val Leu Val Leu Asp Phe Val Thr Pro Thr Pro35 40 45Leu Gly Thr Arg Trp Gly Leu Gly Gly Thr Cys Val Asn Val Gly Cys50 55 60Ile Pro Lys Lys Leu Met His Gln Ala Ala Leu Leu Gly Gln Ala Leu65 70 75 80Lys Asp Ser Arg Asn Tyr Gly Trp Lys Val Glu Asp Thr Val Lys His85 90 95Asp Trp Glu Lys Met Thr Glu Ser Val Gln Ser His Ile Gly Ser Leu100 105 110Asn Trp Gly Tyr Arg Val Ala Leu Arg Glu Lys Lys Val Val Tyr Glu115 120 125Asn Ala Tyr Gly Arg Phe Ile Gly Pro His Arg Ile Val Ala Thr Asn130 135 140Asn Lys Gly Lys Glu Lys Ile Tyr Ser Ala Glu Arg Phe Leu Ile Ala145 150 155160Thr Gly Glu Arg Pro Arg Tyr Leu Gly Ile Pro Gly Asp Lys Glu Tyr165 170 175Cys Ile Ser Ser Asp Asp Leu Phe Ser Leu Pro Tyr Cys Pro Gly Lys180 185 190Thr Leu Val Val Gly Ala Ser Tyr Val Ala Leu Glu Cys Ala Gly Phe195 200 205Leu Ala Gly Ile Gly Leu Asp Val Thr Val Met Val Arg Ser Ile Leu210 215 220Leu Arg Gly Phe Asp Gln Asp Met Ala Asn Lys Ile Gly Glu His Met225 230 235 240Glu Glu His Gly Ile Lys Phe Ile Arg Gln Phe Val Pro Thr Lys Ile245 250 255Glu Gln Ile Glu Ala Gly Thr Pro Gly Arg Leu Arg Val Thr Ala Gln260 265 270Ser Thr Asn Ser Glu Glu Thr Ile Glu Gly Glu Phe Asn Thr Val Leu275 280 285Leu Ala Val Gly Arg Asp Ser Cys Thr Arg Thr Ile Gly Leu Glu Thr290 295 300Val Gly Val Lys Ile Asn Glu Lys Thr Gly Lys Ile Pro Val Thr Asp305 310 315 320Glu Glu Gln Thr Asn Val Pro Tyr Ile Tyr Ala Ile Gly Asp Ile Leu325 330 335Glu Gly Lys Leu Glu Leu Thr Pro Val Ala Ile Gln Ala Gly Arg Leu340 345 350Leu Ala Gln Arg Leu Tyr Gly Gly Ser Asn Val Lys Cys Asp Tyr Asp355 360 365Asn Val Pro Thr Thr Val Phe Thr Pro Leu Glu Tyr Gly Cys Cys Gly370 375 380Leu Ser Glu Glu Lys Ala Val Glu Lys Phe Gly Glu Glu Asn Ile Glu385 390 395 400Val Tyr His Ser Phe Phe Trp Pro Leu Glu Trp Thr Val Pro Ser Arg405 410 415Asp Asn Asn Lys Cys Tyr Ala Lys Ile Ile Cys Asn Leu Lys Asp Asp420 425 430Glu Arg Val Val Gly Phe His Val Leu Gly Pro Asn Ala Gly Glu Val435 440 445Thr Gln Gly Phe Ala Ala Ala Leu Lys Cys Gly Leu Thr Lys Gln Gln450 455 460Leu Asp Ser Thr Ile Gly Ile His Pro Val Cys Ala Glu Ile Phe Thr465 470 475 480Thr Leu Ser Val Thr Lys Arg Ser Gly Gly Asp Ile Leu Gln Ser Gly485 490 495Cys Cys Gly210307211497212PRT213褐鼠220221VARIANT222497223Xaa＝任何胺基酸400307Met Asn Asp Ser Lys Asp Ala Pro Lys Ser Tyr Asp Phe Asp Leu Ile1 5 10 15Ile Ile Gly Gly Gly Ser Gly Gly Leu Ala Ala Ala Lys Glu Ala Ala20 25 30Lys Phe Asp Lys Lys Val Met Val Leu Asp Phe Val Thr Pro Thr Pro35 40 45Leu Gly Thr Asn Gly Gly Leu Gly Gly Thr Cys Val Asn Val Gly Cys50 55 60Ile Pro Lys Lys Leu Met His Gln Ala Ala Leu Leu Gly Gln Ala Leu65 70 75 80Lys Asp Ser Arg Asn Tyr Gly Trp Lys Leu Glu Asp Thr Val Lys His85 90 95Asp Trp Glu Lys Met Thr Glu Ser Val Gln Asn His Ile Gly Ser Leu100 105 110Asn Trp Gly Tyr Arg Val Ala Leu Arg Glu Lys Lys Val Val Tyr Glu115 120 125Asn Ala Tyr Gly Lys Phe Ile Gly Pro His Lys Ile Met Ala Thr Asn130 135 140Asn Lys Gly Lys Glu Lys Val Tyr Ser Ala Glu Arg Phe Leu Ile Ala145 150 155 160Thr Gly Glu Arg Pro Arg Tyr Leu Gly Ile Pro Gly Asp Lys Glu Tyr165 170 175Cys Ile Ser Ser Asp Asp Leu Phe Ser Leu Pro Tyr Cys Pro Gly Lys180 185 190Thr Leu Val Val Gly Ala Ser Tyr Val Ala Leu Glu Cys Ala Gly Phe195 200 205Leu Ala Gly Ile Gly Leu Asp Val Thr Val Met Val Arg Ser Ile Leu210 215 220Leu Arg Gly Phe Asp Gln Asp Met Ala Asn Lys Ile Gly Glu His Met225 230 235 240Glu Glu His Gly Ile Lys Phe Ile Arg Gln Phe Val Pro Thr Lys Ile245 250 255Glu Gln Ile Glu Ala Gly Thr Pro Gly Arg Leu Lys Val Thr Ala Lys260 265 270Ser Thr Asn Ser Glu Glu Thr Ile Glu Asp Glu Phe Asn Thr Val Leu275 280 285Leu Ala Val Gly Arg Asp Ser Cys Thr Arg Thr Ile Gly Leu Glu Thr290 295 300Val Gly Val Lys Ile Asn Glu Lys Thr Gly Lys Ile Pro Val Thr Asp305 310 315 320Glu Glu Gln Thr Asn Val Pro Tyr Ile Tyr Ala Ile Gly Asp Ile Leu325 330 335Glu Gly Lys Leu Glu Leu Thr Pro Val Ala Ile Gln Ala Gly Arg Leu340 345 350Leu Ala Gln Arg Leu Tyr Gly Gly Ser Thr Val Lys Cys Asp Tyr Asp355 360 365Asn Val Pro Thr Thr Val Phe Thr Pro Leu Glu Tyr Gly Cys Cys Gly370 375 380Leu Ser Glu Glu Lys Ala Val Glu Lys Phe Gly Glu Glu Asn Ile Glu385 390 395 400Val Tyr His Ser Phe Phe Trp Pro Leu Glu Trp Thr Val Pro Ser Arg405 410 415Asp Asn Asn Lys Cys Tyr Ala Lys Val Ile Cys Asn Leu Lys Asp Asn420 425 430Glu Arg Val Val Gly Phe His Val Leu Gly Pro Asn Ala Gly Glu Val435 440 445Thr Gln Gly Phe Ala Ala Ala Leu Lys Cys Gly Leu Thr Lys Gln Gln450 455 460Leu Asp Ser Thr Ile Gly Ile His Pro Val Cys Ala Glu Ile Phe Thr465 470 475 480Thr Leu Ser Val Thr Lys Arg Ser Gly Gly Asp Ile Leu Gln Ser Gly
485 490495Xaa210308211176212PRT213褐鼠400308Arg Ile His Ala Gly Gly Ala Gly Arg Arg Arg Gly Gly Ala Arg Arg1 5 10 15Ala Gly Val Phe Ile Leu Leu Ala His Pro Asn Lys Lys Gly Leu Leu20 25 30Arg Lys Leu Ser Thr Met Asn Asp Ser Lys Asp Ala Pro Lys Ser Tyr35 40 45Asp Phe Asp Leu Ile Ile Ile Gly Gly Gly Ser Gly Gly Leu Ala Ala50 55 60Ala Lys Glu Ala Ala Lys Phe Asp Lys Lys Val Met Val Leu Asp Phe65 70 75 80Val Thr Pro Thr Pro Leu Gly Thr Arg Trp Gly Leu Gly Gly Thr Cys85 90 95Val Asn Val Gly Cys Ile Pro Lys Lys Leu Met His Gln Ala Ala Leu100 105 110Leu Gly Gln Ala Leu Lys Asp Ser Arg Asn Tyr Gly Trp Lys Leu Glu115 120 125Asp Thr Val Lys His Asp Trp Glu Lys Met Thr Glu Ser Val Gln Asn130 135 140His Ile Gly Ser Leu Asn Trp Gly Tyr Arg Val Ala Leu Arg Glu Lys145 150 155 160Lys Val Val Tyr Glu Asn Ala Tyr Gly Lys Phe Ile Gly Pro His Lys165 170 175210309211498212PRT213褐鼠220221VARIANT222497223Xaa＝任何胺基酸400309Met Asn Asp Ser Lys Asp Ala Pro Lys Ser Tyr Asp Phe Asp Leu Ile1 5 10 15Ile Ile Gly Gly Gly Ser Gly Gly Leu Ala Ala Ala Lys Glu Ala Ala20 25 30Lys Phe Asp Lys Lys Val Met Val Leu Asp Phe Val Thr Pro Thr Pro35 40 45Leu Gly Thr Asn Gly Gly Leu Gly Gly Thr Cys Val Asn Val Gly Cys50 55 60Ile Pro Lys Lys Leu Met His Gln Ala Ala Leu Leu Gly Gln Ala Leu65 70 75 80Lys Asp Ser Arg Asn Tyr Gly Trp Lys Leu Glu Asp Thr Val Lys His85 90 95Asp Trp Glu Lys Met Thr Glu Ser Val Gln Asn His Ile Gly Ser Leu100 105 110Asn Trp Gly Tyr Arg Val Ala Leu Arg Glu Lys Lys Val Val Tyr Glu115 120 125Asn Ala Tyr Gly Lys Phe Ile Gly Pro His Lys Ile Met Ala Thr Asn130 135 140Asn Lys Gly Lys Glu Lys Val Tyr Ser Ala Glu Arg Phe Leu Ile Ala145 150 155 160Thr Gly Glu Arg Pro Arg Tyr Leu Gly Ile Pro Gly Asp Lys Glu Tyr
165 170 175Cys Ile Ser Ser Asp Asp Leu Phe Ser Leu Pro Tyr Cys Pro Gly Lys180 185 190Thr Leu Val Val Gly Ala Ser Tyr Val Ala Leu Glu Cys Ala Gly Phe195 200 205Leu Ala Gly Ile Gly Leu Asp Val Thr Val Met Val Arg Ser Ile Leu210 215 220Leu Arg Gly Phe Asp Gln Asp Met Ala Asn Lys Ile Gly Glu His Met225 230 235 240Glu Glu His Gly Ile Lys Phe Ile Arg Gln Phe Val Pro Thr Lys Ile245 250 255Glu Gln Ile Glu Ala Gly Thr Pro Gly Arg Leu Lys Val Thr Ala Lys260 265 270Ser Thr Asn Ser Glu Glu Thr Ile Glu Asp Glu Phe Asn Thr Val Leu275 280 285Leu Ala Val Gly Arg Asp Ser Cys Thr Arg Thr Ile Gly Leu Glu Thr290 295 300Val Gly Val Lys Ile Asn Glu Lys Thr Gly Lys Ile Pro Val Thr Asp305 310 315 320Glu Glu Gln Thr Asn Val Pro Tyr Ile Tyr Ala Ile Gly Asp Ile Leu325 330 335Glu Gly Lys Leu Glu Leu Thr Pro Val Ala Ile Gln Ala Gly Arg Leu340 345 350Leu Ala Gln Arg Leu Tyr Gly Gly Ser Thr Val Lys Cys Asp Tyr Asp355 360 365Asn Val Pro Thr Thr Val Phe Thr Pro Leu Glu Tyr Gly Cys Cys Gly370 375 380Leu Ser Glu Glu Lys Ala Val Glu Lys Phe Gly Glu Glu Asn Ile Glu385 390 395 400Val Tyr His Ser Phe Phe Trp Pro Leu Glu Trp Thr Val Pro Ser Arg405 410 415Asp Asn Asn Lys Cys Tyr Ala Lys Val Ile Cys Asn Leu Lys Asp Asn420 425 430Glu Arg Val Val Gly Phe His Val Leu Gly Pro Asn Ala Gly Glu Val435 440 445Thr Gln Ala Leu Gln Pro Leu Lys Cys Gly Leu Thr Lys Gln Gln Leu450 455 460Asp Ser Thr Ile Gly Ile His Pro Val Cys Ala Glu Ile Phe Thr Thr465 470 475 480Leu Ser Val Thr Lys Arg Ser Gly Gly Asp Ile Leu Gln Ser Gly Cys485 490 495Xaa Gly21031021111212PRT213褐鼠400310Met Asn Asp Ser Lys Asp Ala Pro Lys Ser Tyr1 5 10210311211496212PRT213褐鼠400311Met Asn Asp Ser Lys Asp Ala Pro Lys Ser Tyr Asp Phe Asp Leu Ile1 5 10 15Ile Ile Gly Gly Gly Ser Gly Gly Leu Ala Ala Ala Lys Glu Ala Ala20 25 30Lys Phe Asp Lys Lys Val Met Val Leu Asp Phe Val Thr Pro Thr Pro35 40 45Leu Gly Thr Asn Gly Gly Leu Gly Gly Thr Cys Val Asn Val Gly Cys50 55 60Ile Pro Lys Lys Leu Met His Gln Ala Ala Leu Leu Gly Gln Ala Leu65 70 75 80Lys Asp Ser Arg Asn Tyr Gly Trp Lys Leu Glu Asp Thr Val Lys His85 90 95Asp Trp Glu Lys Met Thr Glu Ser Val Gln Asn His Ile Gly Ser Leu100 105 110Asn Trp Gly Tyr Arg Val Ala Leu Arg Glu Lys Lys Val Val Tyr Glu115 120 125Asn Ala Tyr Gly Lys Phe Ile Gly Pro His Lys Ile Met Ala Thr Asn130 135 140Asn Lys Gly Lys Glu Lys Val Tyr Ser Ala Glu Arg Phe Leu Ile Ala145 150 155 160Thr Gly Glu Arg Pro Arg Tyr Leu Gly Ile Pro Gly Asp Lys Glu Tyr165 170 175Cys Ile Ser Ser Asp Asp Leu Phe Ser Leu Pro Tyr Cys Pro Gly Lys180 185 190Thr Leu Val Val Gly Ala Ser Tyr Val Ala Leu Glu Cys Ala Gly Phe195 200 205Leu Ala Gly Ile Gly Leu Asp Val Thr Val Met Val Arg Ser Ile Leu210 215 220Leu Arg Gly Phe Asp Gln Asp Met Ala Asn Lys Ile Gly Glu His Met225 230 235 240Glu Glu His Gly Ile Lys Phe Ile Arg Gln Phe Val Pro Thr Lys Ile245 250 255Glu Gln Ile Glu Ala Gly Thr Pro Gly Arg Leu Lys Val Thr Ala Lys260 265 270Ser Thr Asn Ser Glu Glu Thr Ile Glu Asp Glu Phe Asn Thr Val Leu275 280 285Leu Ala Val Gly Arg Asp Ser Cys Thr Arg Thr Ile Gly Leu Glu Thr290 295 300Val Gly Val Lys Ile Asn Glu Lys Thr Gly Lys Ile Pro Val Thr Asp305 310 315 320Glu Glu Gln Thr Asn Val Pro Tyr Ile Tyr Ala Ile Gly Asp Ile Leu325 330 335Glu Gly Lys Leu Glu Leu Thr Pro Val Ala Ile Gln Ala Gly Arg Leu340 345 350Leu Ala Gln Arg Leu Tyr Gly Gly Ser Thr Val Lys Cys Asp Tyr Asp355 360 365Asn Val Pro Thr Thr Val Phe Thr Pro Leu Glu Tyr Gly Cys Cys Gly370 375 380Leu Ser Glu Glu Lys Ala Val Glu Lys Phe Gly Glu Glu Asn Ile Glu385 390 395 400Val Tyr His Ser Phe Phe Trp Pro Leu Glu Trp Thr Val Pro Ser Arg405 410 415Asp Asn Asn Lys Cys Tyr Ala Lys Val Ile Cys Asn Leu Lys Asp Asn420 425 430Glu Arg Val Val Gly Phe His Val Leu Gly Pro Asn Ala Gly Glu Val435 440 445Thr Gln Ala Leu Gln Pro Leu Lys Cys Gly Leu Thr Lys Gln Gln Leu450 455 460Asp Ser Thr Ile Gly Ile His Pro Val Cys Ala Glu Ile Phe Thr Thr465 470 475 480Leu Ser Val Thr Lys Arg Ser Gly Gly Asp Ile Leu Gln Ser Gly Cys485 490 495210312211526212PRT213褐鼠220221VARIANT222525223Xaa＝任何胺基酸400312Met Ala Ala Ile Val Ala Ala Leu Arg Gly Ser Ser Gly Arg Phe Argl 5 10 15Pro Gln Thr Arg Val Leu Thr Arg Gly Thr Arg Gly Ala Ala Gly Ala20 25 30Ala Ser Ala Ala Gly Gly Gln Gln Asn Phe Asp Leu Leu Val Ile Gly35 40 45Gly Gly Ser Gly Gly Leu Ala Cys Ala Lys Glu Ala Ala Gln Leu Gly50 55 60Arg Lys Val Ala Val Ala Asp Tyr Val Glu Pro Ser Pro Arg Gly Thr65 70 75 80Lys Trp Gly Leu Gly Gly Thr Cys Val Asn Val Gly Cys Ile Pro Lys85 90 95Lys Leu Met His Gln Ala Ala Leu Leu Gly Gly Met Ile Arg Asp Ala100 105 110Gln His Tyr Gly Trp Glu Val Ala Gln Pro Val Gln His Asn Trp Lys115 120 125Ala Met Ala Glu Ala Val Gln Asn His Val Lys Ser Leu Asn Trp Gly130 135 140His Arg Val Gln Leu Gln Asp Arg Lys Val Lys Tyr Phe Asn Ile Lys145 150 155 160Ala Ser Phe Val Asn Glu His Thr Val His Gly Val Asp Lys Ala Gly165 170 175Lys Val Thr Gln Leu Ser Ala Lys His Ile Val Ile Ala Thr Gly Gly180 185 190Arg Pro Lys Tyr Pro Thr Gln Val Lys Gly Ala Leu Glu His Gly Ile195 200 205Thr Ser Asp Asp Ile Phe Trp Leu Lys Glu Ser Pro Gly Lys Thr Leu210 215 220Val Val Gly Ala Ser Tyr Val Ala Leu Glu Cys Ala Gly Phe Leu Thr225 230 235 240Gly Ile Gly Leu Asp Thr Thr Val Met Met Arg Ser Val Pro Leu Arg245 250 255Gly Phe Asp Gln Gln Met Ala Ser Leu Val Thr Glu His Met Glu Ser260 265 270His Gly Thr Arg Phe Leu Lys Gly Cys Val Pro Ser Leu Ile Arg Lys275 280 285Leu Pro Thr Asn Gln Leu Gln Val Thr Trp Glu Asp Leu Ala Ser Gly290 295 300Lys Glu Asp Val Gly Thr Phe Asp Thr Val Leu Trp Ala Ile Gly Arg305 310 315 320Val Pro Glu Thr Arg Asn Leu Asn Leu Glu Lys Ala Gly Val Asn Thr325 330 335Asn Pro Lys Asn Gln Lys Ile Ile Val Asp Ala Gln Glu Ala Thr Ser340 345 350Val Pro His Ile Tyr Ala Ile Gly Asp Val Ala Glu Gly Arg Pro Glu355 360 365Leu Thr Pro Thr Ala Ile Lys Ala Gly Lys Leu Leu Ala Gln Arg Leu370 375 380Phe Gly Lys Ser Ser Thr Leu Met Asn Tyr Ser Asn Val Pro Thr Thr385 390 395 400Val Phe Thr Pro Leu Glu Tyr Gly Cys Val Gly Leu Ser Glu Glu Glu405 410 415Ala Val Ala Leu His Gly Gln Glu His Ile Glu Val Tyr His Ala Tyr420 425 430Tyr Lys Pro Leu Glu Phe Thr Val Ala Asp Arg Asp Ala Ser Gln Cys435 440 445Tyr Ile Lys Met Val Cys Met Arg Glu Pro Pro Gln Leu Val Leu Gly450 455 460Leu His Phe Leu Gly Pro Asn Ala Gly Glu Val Thr Gln Gly Phe Ala465 470 475 480Leu Gly Ile Gln Cys Gly Ala Ser Tyr Ala Gln Val Met Gln Thr Val485 490 495Gly Ile His Pro Thr Cys Ser Glu Glu Val Val Lys Leu His Ile Ser500 505 510Lys Arg Ser Gly Leu Asp Pro Thr Val Thr Gly Cys Xaa Gly515 520 525210313211499212PRT213野豬220221VARIANT222498223Xaa＝任何胺基酸400313Met Asn Gly Ala Glu Glu Leu Pro Glu Met Tyr Asp Tyr Asp Leu Ile1 5 10 15Ile Ile Gly Gly Gly Ser Gly Gly Leu Ala Ala Ala Lys Glu Ala Ala20 25 30Arg Phe Asn Lys Arg Val Met Val Leu Asp Phe Val Thr Pro Thr Pro35 40 45Leu Gly Thr Arg Trp Gly Leu Gly Gly Thr Cys Val Asn Val Ser Cys50 55 60Ile Pro Lys Lys Leu Met His Gln Ala Ala Leu Leu Gly Gln Ala Leu65 70 75 80Arg Asp Ser Arg Asn Tyr Gly Trp Asn Val Glu Glu Thr Ile Lys His85 90 95Asp Trp Glu Arg Met Thr Glu Ala Val Gln Asn His Ile Gly Ser Leu100 105 110Asn Trp Gly Tyr Arg Val Ala Leu Arg Glu Lys Lys Val Thr Tyr Glu115 120 125Asn Ala Tyr Gly Gln Phe Val Gly Pro His Arg Ile Lys Ala Thr Asn130 135 140Asn Lys Gly Lys Glu Lys Ile Tyr Ser Ala Glu Lys Phe Leu Ile Ala145 150 155 160Thr Gly Glu Arg Pro Arg Tyr Leu Gly Ile Pro Gly Asp Lys Glu Tyr165 170 175Cys Ile Ser Ser Asp Asp Leu Phe Ser Leu Pro Tyr Cys Pro Gly Lys180 185 190Thr Leu Val Val Gly Ala Ser Tyr Val Ala Leu Glu Cys Ala Gly Phe195 200 205Leu Ala Gly Ile Gly Leu Asp Val Thr Val Met Val Arg Ser Ile Leu210 215 220Leu Arg Gly Phe Asp Gln Asp Met Ala Asn Lys Ile Gly Glu His Met225 230 235 240Glu Glu His Gly Ile Lys Phe Ile Arg Gln Phe Val Pro Ile Lys Val245 250 255Glu Gln Ile Glu Ala Gly Thr Pro Gly Arg Leu Arg Val Val Ala Gln260 265 270Ser Thr Asn Ser Glu Glu Ile Ile Glu Gly Glu Tyr Asn Thr Val Met275 280 285Leu Ala Ile Gly Arg Asp Ala Cys Thr Arg Lys Ile Gly Leu Glu Thr290 295 300Val Gly Val Lys Ile Asn Glu Lys Thr Gly Lys Ile Pro Val Thr Asp305 310 315 320Glu Glu Gln Thr Asn Val Pro Tyr Ile Tyr Ala Ile Gly Asp Ile Leu325 330 335Glu Asp Lys Val Glu Leu Thr Pro Val Ala Ile Gln Ala Gly Arg Leu340 345 350Leu Ala Gln Arg Leu Tyr Ala Gly Ser Thr Val Lys Cys Asp Tyr Glu355 360 365Asn Val Pro Thr Thr Val Phe Thr Pro Leu Glu Tyr Gly Ala Cys Gly370 375 380Leu Ser Glu Glu Lys Ala Val Glu Lys Phe Gly Glu Glu Asn Ile Glu385 390 395 400Val Tyr His Ser Tyr Phe Trp Pro Leu Glu Trp Thr Ile Pro Ser Arg405 410 415Asp Asn Asn Lys Cys Tyr Ala Lys Ile Ile Cys Asn Thr Lys Asp Asn420 425 430Glu Arg Val Val Gly Phe His Val Leu Gly Pro Asn Ala Gly Glu Val
435 440 445Thr Gln Gly Phe Ala Ala Ala Leu Lys Cys Gly Leu Thr Lys Lys Gln450 455 460Leu Asp Ser Thr Ile Gly Ile His Pro Val Cys Ala Glu Val Phe Thr465 470 475 480Thr Leu Ser Val Thr Lys Arg Ser Gly Ala Ser Ile Leu Gln Ala Gly485 490 495Cys Xaa Gly
權利要求
1.製備與油體結合的重組多聚體蛋白質複合物的方法，所述方法包括(a)在包含油體的細胞中產生第一重組多肽和第二重組多肽，其中所述第一重組多肽能夠與所述第二重組多肽結合形成所述多聚體蛋白質複合物；和(b)通過能夠與所述油體及所述第一重組多肽結合的油體靶向蛋白使所述多聚體蛋白質複合物和油體結合。
2.權利要求1的方法，其還包括(c)分離與所述重組多聚體蛋白質複合物結合的所述油體。
3.權利要求1的方法，其中所述多聚體蛋白質複合物與能夠從包含油體的所述細胞中獲得的油體結合。
4.權利要求1的方法，其中所述多聚體蛋白質複合物在細胞內與所述油體結合。
5.權利要求1的方法，其中所述第二重組多肽與能夠結合油體和所述第二重組多肽的第二油體靶向蛋白結合。
6.權利要求5的方法，其中所述油體靶向蛋白每個均為油體蛋白或免疫球蛋白。
7.權利要求6的方法，其中所述油體靶向蛋白是油質蛋白或caleosin。
8.權利要求1的方法，其中所述油體靶向蛋白是油質蛋白或caleosin而所述第一重組多肽與所述油質蛋白或caleosin融合。
9.權利要求8的方法，其中所述第二重組多肽與能結合油體的第二油質蛋白或第二caleosin融合。
10.權利要求1的方法，其中所述第一和第二重組多肽以包含所述第一和第二重組多肽的多聚體融合蛋白形式產生。
11.權利要求1的方法，其中所述多聚體蛋白質複合物是異源多聚體蛋白質複合物。
12.權利要求11的方法，其中所述異源多聚體蛋白質複合物是具有酶學活性的氧還蛋白複合物或免疫球蛋白。
13.權利要求1的方法，其中所述第一重組多肽能夠與所述第二重組多肽在所述細胞中結合。
14.權利要求1的方法，其中所述第一重組多肽是硫氧還蛋白而所述第二重組多肽是硫氧還蛋白還原酶。
15.權利要求14的方法，其中所述硫氧還蛋白選自SEQ ID NO38，42，46，50和SEQ ID NO52-194。
16.權利要求14的方法，其中所述硫氧還蛋白還原酶選自SEQ IDNO8，9，10，40，44，48，50和SEQ ID NO195-313。
17.權利要求1的方法，其中所述細胞是植物細胞。
18.權利要求1的方法，其中所述細胞是紅花細胞。
19.權利要求1的方法，其中所述第一重組多肽是免疫球蛋白多肽鏈。
20.權利要求1的方法，其中所述第一重組多肽是免疫球蛋白輕鏈或其免疫學活性部分，而所述第二重組多肽是免疫球蛋白重鏈或其免疫學活性部分。
21.權利要求19的方法，其中所述油體靶向蛋白包含A蛋白、L蛋白或G蛋白。
22.在細胞中表達包含第一和第二重組多肽的重組多聚體蛋白質複合物的方法，所述方法包括(a)向細胞中引入包含如下成分的第一嵌合核酸序列(i)在所述細胞中能夠調節轉錄的第一核酸序列；(ii)與第一核酸序列可操作連接的、編碼第一重組多肽的第二核酸序列；(b)向所述細胞中引入包含如下成分的第二嵌合核酸序列(i)能夠在所述細胞中調節轉錄的第三核酸序列；(ii)與第三核酸序列可操作連接的、編碼第二重組多肽的第四核酸序列；(c)在允許所述第一和第二重組多肽在包含油體的子代細胞中表達的條件下培養所述細胞，其中所述第一重組多肽和所述第二重組多肽能夠形成多聚體蛋白質複合物；和(d)通過能夠與所述油體和所述第一重組多肽結合的油體靶向蛋白，使所述第一重組多肽和油體結合。
23.權利要求22的方法，其還包括(e)從所述子代細胞中分離包含所述多聚體蛋白質複合物的油體。
24.權利要求22的方法，其中所述多聚體蛋白質複合物與能夠從包含油體的所述子代細胞中獲得的所述油體結合。
25.權利要求22的方法，其中所述油體與所述多聚體蛋白質複合物在細胞內結合。
26.權利要求22的方法，其中所述第二重組多肽與能夠結合油體和所述第二重組多肽的第二油體靶向蛋白結合。
27.權利要求26的方法，其中所述油體靶向蛋白每個均選自油體蛋白或免疫球蛋白。
28.權利要求27的方法，其中所述油體蛋白是油質蛋白或caleosin。
29.權利要求28的方法，其中所述第一重組多肽與所述油質蛋白或caleosin融合。
30.權利要求29的方法，其中所述第二重組多肽與能結合油體的第二油質蛋白或第二caleosin融合。
31.權利要求22的方法，其中所述第一和第二重組多肽以包含所述第一和第二重組多肽的多聚體融合蛋白形式產生。
32.權利要求22的方法，其中所述第一和第二重組多肽形成多聚體蛋白質複合物。
33.權利要求32的方法，其中所述多聚體蛋白質複合物是異源多聚體蛋白質複合物。
34.權利要求32的方法，其中所述異源多聚體蛋白質複合物是具有酶學活性的氧還蛋白複合物或免疫球蛋白。
35.權利要求22的方法，其中所述第一重組多肽和所述第二重組多肽能夠在所述子代細胞中形成多聚體蛋白質複合物。
36.權利要求22的方法，其中所述第一重組多肽是硫氧還蛋白而所述第二重組多肽是硫氧還蛋白還原酶。
37.權利要求36的方法，其中所述硫氧還蛋白選自SEQ ID NO38，42，46，50和SEQ ID NO52-194。
38.權利要求36的方法，其中所述硫氧還蛋白還原酶選自SEQ IDNO8，9，10，40，44，48，50和SEQ ID NO195-313。
39.權利要求22的方法，其中所述第一重組多肽是免疫球蛋白多肽鏈。
40.權利要求22的方法，其中所述第一重組多肽是免疫球蛋白輕鏈或其免疫學活性部分，而所述第二重組多肽是免疫球蛋白重鏈或其免疫學活性部分。
41.權利要求39的方法，其中所述油體靶向蛋白包含A蛋白、L蛋白或G蛋白。
42.權利要求22的方法，其中所述細胞是植物細胞。
43.權利要求42的方法，其中所述植物細胞是紅花細胞。
44.在植物中生產重組多聚體蛋白質複合物的方法，所述方法包括(a)製備包含如下細胞的第一植物，所述細胞包含油體和第一重組多肽，其中所述第一重組多肽能夠通過油體靶向蛋白與所述油體結合；(b)製備包含如下細胞的第二植物，所述細胞包含油體和第二重組多肽；和(c)使所述第一植物和所述第二植物進行有性雜交產生包含如下細胞的子代植物，所述細胞包含油體，其中所述油體能夠與所述第一重組多肽結合，而所述第一重組多肽能夠與所述第二重組多肽結合形成所述重組多聚體蛋白質複合物。
45.權利要求44的方法，其中所述第二重組多肽能夠通過油體靶向蛋白在所述第二植物中與油體結合。
46.權利要求44的方法，其還包括(d)從所述子代植物中分離包含所述多聚體蛋白質複合物的油體。
47.權利要求44的方法，其中所述油體靶向蛋白選自油體蛋白或免疫球蛋白。
48.權利要求47的方法，其中所述油體蛋白是油質蛋白或caleosin。
49.權利要求48的方法，其中所述第一重組多肽與所述油質蛋白或caleosin融合。
50.權利要求49的方法，其中所述第二重組多肽與能結合油體的第二油質蛋白或第二caleosin融合。
51.權利要求44的方法，其中所述第一和第二重組多肽形成多聚體蛋白質複合物。
52.權利要求51的方法，其中所述多聚體蛋白質複合物是異源多聚體蛋白質複合物。
53.權利要求52的方法，其中所述異源多聚體蛋白質複合物是具有酶學活性的氧還蛋白複合物或免疫球蛋白。
54.權利要求44的方法，其中所述第一重組多肽是硫氧還蛋白而所述第二重組多肽是硫氧還蛋白還原酶。
55.權利要求54的方法，其中所述硫氧還蛋白選自SEQ ID N038，42，46，50和SEQ ID NO52-194。
56.權利要求54的方法，其中所述硫氧還蛋白還原酶選自SEQ IDNO8，9，10，40，44，48，50和SEQ ID NO195-313。
57.權利要求44的方法，其中所述第一重組多肽是免疫球蛋白多肽鏈。
58.權利要求44的方法，其中所述第一重組多肽是免疫球蛋白輕鏈或其免疫學活性部分，而所述第二重組多肽是免疫球蛋白重鏈或其免疫學活性部分。
59.權利要求57的方法，其中所述油體靶向蛋白包含A蛋白、L蛋白或G蛋白。
60.權利要求44的方法，其中所述植物是紅花。
61.編碼多聚體融合蛋白的嵌合核酸序列，所述核酸包含(a)編碼油體靶向蛋白的第一核酸序列；(b)在閱讀框中與第一核酸序列可操作連接的、編碼第一重組多肽的第二核酸序列；(c)在閱讀框中與第二核酸序列連接的、編碼第二重組多肽的第三核酸序列，其中，所述第一和第二重組多肽能夠形成多聚體蛋白質複合物。
62.權利要求61的核酸，其中所述油體靶向蛋白為油體蛋白或免疫球蛋白。
63.權利要求62的核酸，其中所述油體蛋白是油質蛋白或caleosin。
64.權利要求63的核酸，其中所述多聚體蛋白質複合物是異源多聚體蛋白質複合物。
65.權利要求61的嵌合核酸序列，其中所述第一和第二重組多肽形成具有酶學活性的異源多聚體氧還蛋白複合物或免疫球蛋白。
66.權利要求65的嵌合核酸序列，其中所述第一和第二重組多肽是硫氧還蛋白和硫氧還蛋白還原酶。
67.權利要求66的嵌合核酸，其中所述硫氧還蛋白選自SEQ ID NO38，42，46，50和SEQ ID NO52-194。
68.權利要求66的嵌合核酸，其中所述硫氧還蛋白還原酶選自SEQID NO8，9，10，40，44，48，50和SEQ ID NO195-313。
69.權利要求65的嵌合核酸，其中所述第一重組多肽是免疫球蛋白多肽鏈。
70.權利要求65的嵌合核酸，其中所述第一重組多肽是免疫球蛋白輕鏈或其免疫學活性部分，而所述第二重組多肽是免疫球蛋白重鏈或其免疫學活性部分。
71.權利要求69的嵌合核酸，其中所述油體靶向蛋白包含A蛋白、L蛋白或G蛋白。
72.權利要求61的核酸，其中在編碼油體靶向蛋白的所述核酸序列和編碼第一重組多肽的所述核酸序列之間放置有編碼迴避油體表面的接頭胺基酸序列的接頭核酸序列。
73.權利要求72的核酸，其中所述迴避油體表面的接頭胺基酸序列基本上帶負電荷，或具有至少35kd的分子量。
74.權利要求73的核酸，其中所述基因融合物還包含如下接頭核酸序列，該接頭核酸序列編碼能夠被酶或化學物質特異切割的胺基酸序列，其中該接頭序列位於所述迴避油體表面的接頭胺基酸序列和編碼第一重組多肽的所述序列之間。
75.重組多聚體融合蛋白，其包含(i)油體靶向蛋白或其片斷，(ii)第一重組多肽和(iii)第二重組多肽，其中所述第一和第二重組多肽能夠形成多聚體蛋白質複合物。
76.權利要求75的重組多聚體融合蛋白，其中所述油體靶向蛋白選自油體蛋白或免疫球蛋白。
77.權利要求76的重組多聚體融合蛋白，其中所述油體蛋白是油質蛋白或caleosin。
78.權利要求77的重組多聚體融合蛋白，其中所述多聚體融合蛋白是異源多聚體融合蛋白。
79.權利要求78的重組異源多聚體融合蛋白，其中所述第一和第二重組多肽形成具有酶學活性的異源多聚體氧還蛋白複合物或免疫球蛋白。
80.權利要求79的重組融合多肽，其中所述第一重組多肽是硫氧還蛋白而所述第二重組多肽是硫氧還蛋白還原酶。
81.權利要求80的重組融合多肽，其中所述硫氧還蛋白選自SEQID NO38，42，46，50和SEQ ID NO52-194。
82.權利要求80的重組融合多肽，其中所述硫氧還蛋白還原酶選自SEQ ID NO8，9，10，40，44，48，50和SEQ ID NO195-313。
83.權利要求75的重組融合多肽，其中在所述油體靶向蛋白和所述第一重組多肽之間放置有迴避油體表面的接頭胺基酸序列。
84.權利要求83的重組融合多肽，其中所述迴避油體表面的接頭胺基酸序列基本上帶負電荷，或具有至少35kd的分子量。
85.權利要求84的重組融合多肽，其中該融合多肽還包含能夠被酶或化學物質特異切割的接頭胺基酸序列，其中該接頭序列位於該迴避油體表面的接頭胺基酸序列和所述第一重組多肽之間。
86.包含多聚體蛋白複合物的分離的油體，所述多聚體蛋白複合物包含(i)油體靶向蛋白和(ii)第一重組多肽，而所述油體還包含第二重組多肽，其中所述第一和第二重組多肽能形成多聚體蛋白質複合物。
87.權利要求86的分離的油體，其中所述油體靶向蛋白是油體蛋白或免疫球蛋白。
88.權利要求87的分離的油體，其中所述油體蛋白是油質蛋白或caleosin。
89.權利要求88的分離的油體，其中所述第一重組多肽與所述油質蛋白或caleosin融合。
90.權利要求86的分離的油體，其中所述第一重組多肽與所述第二重組多肽融合。
91.權利要求90的分離的油體，其中所述多聚體蛋白質複合物是異源多聚體蛋白質複合物。
92.權利要求91的分離的油體，其中所述異源多聚體蛋白質複合物是具有酶學活性的氧還蛋白複合物或免疫球蛋白。
93.分離的油體，其包含(a)包含與第一重組多肽融合的第一油體靶向蛋白的第一融合蛋白；和(b)包含與第二重組多肽融合的第二油體靶向蛋白的第二融合蛋白，其中所述第一和第二重組多肽能夠形成多聚體蛋白質複合物。
94.權利要求93的分離的油體，其中所述第一油體靶向蛋白是油體蛋白或免疫球蛋白。
95.權利要求93的分離的油體，其中所述第一油體蛋白是油質蛋白或caleosin。
96.權利要求93的分離的油體，其中所述多聚體蛋白質複合物是異源多聚體蛋白質複合物。
97.權利要求93的分離的油體，其中所述第一和第二重組多肽形成具有酶學活性的異源多聚體氧還蛋白複合物或免疫球蛋白。
98.權利要求93的分離的油體，其中所述第一重組多肽是硫氧還蛋白而所述第二重組多肽是硫氧還蛋白還原酶。
99.權利要求98的油體，其中所述硫氧還蛋白選自SEQ ID NO38，42，46，50和SEQ ID NO52-194。
100.權利要求98的油體，其中所述硫氧還蛋白還原酶選自SEQ IDNO8，9，10，40，44，48，50和SEQ ID NO195-313。
101.權利要求93的油體，其中所述第一重組多肽是免疫球蛋白多肽鏈。
102.權利要求93的油體，其中所述第一重組多肽是免疫球蛋白輕鏈或其免疫學活性部分，而所述第二重組多肽是免疫球蛋白重鏈或其免疫學活性部分。
103.權利要求101的油體，其中所述油體靶向蛋白包含A蛋白、L蛋白或G蛋白。
104.細胞，其包含油體以及(i)油體靶向蛋白、(ii)第一重組多肽和(iii)第二重組多肽，其中(1)所述第一重組多肽能夠與所述油體靶向蛋白結合；且(2)所述第一重組多肽能夠與所述第二重組多肽結合形成多聚體蛋白質複合物。
105.權利要求104的細胞，其中所述油體靶向蛋白是油體蛋白或免疫球蛋白。
106.權利要求105的細胞，其中所述油體蛋白是油質蛋白或caleosin。
107.權利要求104的細胞，其中所述第一重組多肽與所述第二重組多肽融合以致形成多聚體融合蛋白。
108.權利要求107的細胞，其中所述多聚體融合蛋白是異源多聚體融合蛋白。
109.權利要求104的細胞，其中所述第一重組多肽與所述油體靶向蛋白融合。
110.權利要求104的細胞，其中所述第一重組多肽與所述第一油體靶向蛋白融合，而所述第二多肽與第二油體靶向蛋白融合。
111.權利要求104的細胞，其中所述第二重組多肽能夠與第二油體靶向蛋白結合。
112.權利要求104的細胞，其中所述第一和第二重組多肽形成異源多聚體蛋白質複合物。
113.權利要求104的細胞，其中所述異源多聚體蛋白質複合物是具有酶學活性的氧還蛋白複合物或免疫球蛋白。
114.權利要求104的細胞，其中所述第一多肽是硫氧還蛋白而所述第二多肽是硫氧還蛋白還原酶。
115.權利要求114的細胞，其中所述硫氧還蛋白選自SEQ ID NO38，42，46，50和SEQ ID NO52-194。
116.權利要求114的細胞，其中所述硫氧還蛋白還原酶選自SEQ IDNO8，9，10，40，44，48，50和SEQ ID NO195-313。
117.權利要求104的細胞，其中所述第一重組多肽是免疫球蛋白多肽鏈。
118.權利要求104的細胞，其中所述第一重組多肽是免疫球蛋白輕鏈或其免疫學活性部分，而所述第二重組多肽是免疫球蛋白重鏈或其免疫學活性部分。
119.權利要求117的細胞，其中所述油體靶向蛋白包含A蛋白、L蛋白或G蛋白。
120.權利要求104的細胞，其中所述細胞從植物獲得。
121.權利要求104的細胞，其中所述細胞可以從紅花植物獲得。
122.包含權利要求104的細胞的植物。
123.包含權利要求104的細胞的紅花植物。
124.權利要求2的方法，其中所述第一重組多肽是硫氧還蛋白而所述第二重組多肽是硫氧還蛋白還原酶，所述方法還包括(d)配製所述油體用於食品、個人護理產品或藥物組合物的製備中。
125.權利要求124的方法，其中所述硫氧還蛋白選自SEQ ID NO38，42，46，50和SEQ ID NO52-194。
126.權利要求124的方法，其中所述硫氧還蛋白還原酶選自SEQ IDNO8，9，10，40，44，48，50和SEQ ID NO195-313。
127.權利要求124的方法，其中所述配製包括添加NADP或NADPH。
128.權利要求124的方法，其中所述食品是基於奶或小麥的食品。
129.權利要求124的方法，其中所述個人護理產品可減輕對人體表面的氧化壓力或用於增亮皮膚。
130.權利要求124的方法，其中所述藥物組合物用於治療慢性阻塞性肺病(COPD)、白內障、糖尿病、螫刺毒作用、支氣管肺病、惡性腫瘤、銀屑病、再灌注損傷、傷口癒合、膿毒病、GI出血、腸道疾病(IBD)、潰瘍、GERD(胃食管反流病)。
131.包含分離的油體、硫氧還蛋白和硫氧還蛋白還原酶的組合物。
132.權利要求131的組合物，其中所述硫氧還蛋白選自SEQ ID N038，42，46，50和SEQ ID NO52-194。
133.權利要求131的組合物，其中所述硫氧還蛋白還原酶選自SEQID NO8，9，10，40，44，48，50和SEQ ID NO195-313。
134.權利要求131的組合物，其還包含NADP或NADPH。
135.包含權利要求131的組合物的食品、個人護理產品或藥物組合物。
136.權利要求135的食品、個人護理產品或藥物組合物，其還包含NADP或NADPH。
137.權利要求135的食品，其中所述食品是基於奶或小麥的食品。
138.權利要求135的個人護理產品，其中所述個人護理產品可減輕對人體表面的氧化壓力或用於增亮皮膚。
139.權利要求135的藥物組合物，其中所述藥物組合物用於治療慢性阻塞性肺病、白內障、銀屑病或再灌注損傷。
140.權利要求75的多聚體融合蛋白，其中所述融合蛋白含有兩種或多種選自圖5中給出的蛋白質的多肽鏈。
141.降低食物的變應原性的方法，其包括步驟提供權利要求78的分離的油體；和將所述分離的油體加入食物中，由此降低的食物的變應原性。
142.權利要求141的方法，其中所述食物選自小麥麵粉、小麥麵團、奶、乾酪、酸牛奶和冰淇淋。
143.權利要求141的方法，其還包括在實質上缺少NADPH的情況下提供NADH作為輔因子。
144.治療或保護靶對象使其免受氧化壓力的方法，包括步驟提供權利要求46的重組融合多肽；和使該重組融合多肽和易受氧化壓力影響的靶對象接觸，由此達到抵抗氧化壓力的治療或保護作用。
145.權利要求144的方法，其中所述靶對象選自分子、分子複合物、細胞、組織和器官。
146.製備與油體結合的具有酶學活性的氧還蛋白的方法，其包括a)在細胞中產生包含第一氧還蛋白及與它連接的第二氧還蛋白的氧還蛋白融合多肽；b)通過能夠結合所述氧還蛋白融合多肽和所述油體的油體靶向蛋白使所述氧還蛋白融合多肽與油體結合；和c)分離與所述氧還蛋白融合多肽結合的油體。
147.權利要求146的方法，其中所述油體靶向蛋白為油體蛋白或免疫球蛋白。
148.權利要求146的方法，其中所述油體蛋白是油質蛋白或caleosin。
149.權利要求146的方法，其中所述第一氧還蛋白是硫氧還蛋白而所述第二氧還蛋白是硫氧還蛋白還原酶。
150.權利要求149的方法，其中所述硫氧還蛋白選自SEQ ID NO38，42，46，50和SEQ ID NO52-194。
151.權利要求149的方法，其中所述硫氧還蛋白還原酶選自SEQ IDNO8，9，10，40，44，48，50和SEQ ID NO195-313。
152.權利要求146的方法，其中所述細胞是植物細胞。
153.權利要求146的方法，其中所述細胞是紅花細胞。
154.製備與油體結合的氧還蛋白的方法，其包括a)向細胞中引入包含如下成分的嵌合核酸序列1)能夠在所述細胞中調節轉錄的第一核酸序列；2)與第一核酸序列可操作連接的、編碼重組融合多肽的第二核酸序列，第二核酸序列包含(i)編碼足以使所述重組融合多肽靶向油體的油體蛋白部分的核酸序列，和(ii)與(i)連接的、編碼包含相互連接的第一氧還蛋白和第二氧還蛋白的氧還蛋白融合多肽的核酸序列；3)與第二核酸序列可操作連接的能夠在所述細胞中終止轉錄的第三核酸序列；b)在允許所述氧還蛋白融合多肽在包含油體的子代細胞中表達的條件下培養所述細胞；和c)從所述子代細胞中分離包含所述氧還蛋白融合多肽的所述油體。
155.權利要求154的方法，其中在編碼足夠的油體靶向蛋白部分的所述核酸序列和編碼氧還蛋白融合多肽的所述核酸序列之間放置有編碼迴避油體表面的接頭胺基酸序列的接頭核酸序列。
156.權利要求155的方法，其中所述迴避油體表面的接頭胺基酸序列基本上帶負電荷，或具有至少35kd的分子量。
157.權利要求156的方法，其中所述基因融合物還包含編碼能夠被酶或化學物質特異切割的胺基酸序列的接頭核酸序列，其中該接頭序列位於所述迴避油體表面的接頭胺基酸序列和編碼氧還蛋白融合多肽的所述核酸序列之間。
158.權利要求157的方法，其還包括引入可切斷所述氧還蛋白融合多肽和所述油體的酶或化學物質，由此獲得分離的氧還蛋白融合多肽。
159.權利要求154的方法，其中所述油體蛋白是油質蛋白或caleosin。
160.權利要求154的方法，其中所述第一氧還蛋白是硫氧還蛋白而所述第二氧還蛋白是硫氧還蛋白還原酶。
161.權利要求160的方法，其中所述硫氧還蛋白選自SEQ ID NO38，42，46，50和SEQ ID NO52-194。
162.權利要求160的方法，其中所述硫氧還蛋白還原酶選自SEQ IDNO8，9，10，40，44，48，50和SEQ ID NO195-313。
163.權利要求154的方法，其中所述細胞是植物細胞。
164.權利要求154的方法，其中所述硫氧還蛋白和硫氧還蛋白還原酶從鼠耳芥屬植物獲得。
165.權利要求146的方法，其中以氧還蛋白融合多肽的形式產生的第一氧還蛋白比不帶第二氧還蛋白而產生的第一氧還蛋白在活性上高出至少5倍。
166.權利要求146的方法，其還包括d)配製與氧還蛋白融合多肽結合的油體的乳液用於製備能夠治療靶對象的氧化壓力的產品、能夠化學還原靶對象的產品、藥物組合物、個人護理產品或食品。
167.嵌合核酸，其包含1)能夠在宿主細胞中調節轉錄的第一核酸序列；2)與第一核酸序列可操作連接的、編碼重組融合多肽的第二核酸序列，第二核酸序列包含(i)編碼足以使所述重組融合多肽靶向油體的油體蛋白部分的核酸序列和(ii)與(i)連接的、編碼包含相互連接的第一氧還蛋白和第二氧還蛋白的氧還蛋白融合多肽的核酸序列；3)與第二核酸序列可操作連接的、能夠在所述細胞中終止轉錄的第三核酸序列。
168.權利要求167的嵌合核酸，其中所述油體蛋白是油質蛋白或caleosin。
169.權利要求167的嵌合核酸，其中所述第一氧還蛋白是硫氧還蛋白而所述第二氧還蛋白是硫氧還蛋白還原酶。
170.權利要求169的嵌合核酸，其中所述硫氧還蛋白選自SEQ ID NO38，42，46，50和SEQ ID NO52-194。
171.權利要求169的嵌合核酸，其中所述硫氧還蛋白還原酶選自SEQ ID NO8，9，10，40，44，48，50和SEQ ID NO195-313。
172.權利要求167的嵌合核酸，其中所述細胞是植物細胞。
173.權利要求167的嵌合核酸，其中在編碼足夠的油體靶向蛋白部分的所述核酸序列和編碼氧還蛋白融合多肽的所述核酸序列之間放置有編碼迴避油體表面的接頭胺基酸序列的接頭核酸序列。
174.權利要求173的嵌合核酸，其中所述迴避油體表面的接頭胺基酸序列基本上帶負電荷，或具有至少35kd的分子量。
175.權利要求174的嵌合核酸，其中所述基因融合物還包含編碼能夠被酶或化學物質特異切割的胺基酸序列的接頭核酸序列，其中該接頭序列位於該迴避油體表面的接頭胺基酸序列和編碼氧還蛋白融合多肽的所述核酸序列之間。
176.包含權利要求167的嵌合核酸序列的轉基因植物。
177.權利要求176的轉基因植物，其中所述嵌合核酸包含在質體中。
178.包含權利要求167的嵌合核酸的紅花植物。
179.權利要求178的紅花植物，其中所述嵌合核酸包含在質體中。
180.包含權利要求167的嵌合核酸的植物種子。
181.權利要求180的植物種子，其中所述嵌合核酸包含在質體中。
182.包含權利要求168的嵌合核酸的紅花種子。
183.權利要求182的紅花種子，其中所述嵌合核酸包含在質體中。
184.通過權利要求146的方法獲得的油體製品。
185.包含權利要求184的油體製品的食品。
186.包含權利要求184的油體製品的組合物。
187.包含權利要求184的油體製品的個人護理產品。
188.能夠治療靶對象的氧化壓力的產品，其包含權利要求184的油體製品。
189.能夠化學還原靶對象的產品，其包含權利要求184的油體製品。
190.包含權利要求184的產品的去汙劑組合物。
191.清潔物體的方法，包括在促進清潔的條件下向所述物體施用權利要求189的產品。
192.通過權利要求166的方法製備的乳劑製品。
193.包含基因融合物的核酸構建體，其中所述基因融合物包含編碼油體蛋白或其活性片斷的第一區域、以及和第一區域可操作連接的編碼至少一個硫氧還蛋白相關蛋白或其活性片斷的第二區域。
194.權利要求193的構建體，其中所述至少一個硫氧還蛋白相關蛋白是硫氧還蛋白。
195.權利要求194的構建體，其中所述硫氧還蛋白選自SEQ ID NO38，42，46，50和SEQ ID NO52-194。
196.權利要求194的構建體，其中硫氧還蛋白來源於鼠耳芥屬或小麥。
197.權利要求193的構建體，其中所述至少一個硫氧還蛋白相關蛋白是硫氧還蛋白還原酶。
198.權利要求197的構建體，其中所述硫氧還蛋白還原酶選自SEQID NO8，9，10，40，44，48，50和SEQ ID NO195-313。
199.權利要求197的構建體，其中硫氧還蛋白還原酶來源於鼠耳芥屬或小麥。
200.權利要求197的構建體，其中硫氧還蛋白還原酶是NADPH-依賴性硫氧還蛋白還原酶。
201.權利要求193的構建體，其中第二區域編碼硫氧還蛋白和硫氧還蛋白還原酶。
202.權利要求201的構建體，其中硫氧還蛋白和硫氧還蛋白還原酶從麻風分枝桿菌獲得。
203.權利要求201的構建體，其中至少一個硫氧還蛋白相關蛋白是工程化的融合蛋白。
204.權利要求193的構建體，其中第一區域以5』至3』方向位於第二區域之前。
205.權利要求193的構建體，其中第一區域以5』至3』方向位於第二區域之後。
206.權利要求193的構建體，其中該基因融合物還包含編碼第二硫氧還蛋白相關蛋白或其活性片斷的第三區域，而且所述第三區域與第一區域或第二區域或兩者可操作地連接。
207.權利要求193的構建體，其還包含與該基因融合物可操作連接的種子特異性啟動子。
208.權利要求207的構建體，其中啟動子是菜豆蛋白啟動子。
209.權利要求193的構建體，其中至少一個硫氧還蛋白相關蛋白來源於選自鼠耳芥屬和小麥的植物物種。
210.權利要求193的構建體，其中至少一個硫氧還蛋白相關蛋白來源於大腸桿菌。
211.權利要求193的構建體，其還包含可在植物細胞中有效作為終止區域的核酸，該核酸可操作地與所述基因融合物連接。
212.權利要求193的構建體，其中該基因融合物還包含編碼迴避油體表面的接頭胺基酸序列的核酸序列，其中該接頭胺基酸序列位於第一區域和第二區域之間。
213.權利要求212的構建體，其中所述迴避油體表面的接頭胺基酸序列基本上帶負電荷，或具有至少35kd的分子量。
214.權利要求213的構建體，其中所述基因融合物還包含編碼能夠被酶或化學物質特異切割的胺基酸序列的接頭核酸序列，其中該接頭序列位於該迴避油體表面的接頭胺基酸序列和第二區域之間。
215.權利要求193的構建體，其中該基因融合物的區域包含多個密碼子，每個密碼子規定一個胺基酸，其中該區域中的至少一個密碼子是從天然密碼子修飾得到的。
216.權利要求215的構建體，其中該修飾密碼子與所述天然密碼子規定相同的胺基酸，且該修飾密碼子是根據植物的密碼子偏好修飾的。
217.權利要求215的構建體，其中該修飾密碼子與所述天然密碼子規定不同的胺基酸。
218.轉基因植物，其含有包含基因融合物的核酸構建體，其中所述基因融合物包含編碼油體蛋白或其活性片斷的區域、以及與該區域可操作連接的編碼第一硫氧還蛋白相關蛋白或其活性片斷的區域。
219.權利要求218的植物，其中所述硫氧還蛋白相關蛋白是硫氧還蛋白。
220.權利要求219的植物，其中所述硫氧還蛋白選自SEQ ID NO38，42，46，50和SEQ ID NO52-194。
221.權利要求219的植物，其中硫氧還蛋白來源於鼠耳芥屬或小麥。
222.權利要求218的植物，其中所述硫氧還蛋白相關蛋白是硫氧還蛋白還原酶。
223.權利要求222的植物，其中所述硫氧還蛋白還原酶選自SEQ IDNO8，9，10，40，44，48，50和SEQ ID NO195-313。
224.權利要求222的植物，其中硫氧還蛋白還原酶是NADPH-依賴性硫氧還蛋白還原酶。
225.權利要求218的植物，其中該構建體包含在質體中。
226.權利要求218的植物，其中第一硫氧還蛋白相關蛋白是硫氧還蛋白，而且所述構建體還包含編碼硫氧還蛋白還原酶的區域。
227.權利要求226的植物，其中硫氧還蛋白和硫氧還蛋白還原酶從麻風分枝桿菌獲得。
228.權利要求226的植物，其中該硫氧還蛋白相關蛋白是工程化的融合蛋白。
229.權利要求218的植物，其中第一區域以5』至3』方向位於第二區域之前。
230.權利要求218的植物，其中第一區域以5』至3』方向位於第二區域之後。
231.權利要求218的植物，其中該基因融合物還包含編碼第二硫氧還蛋白相關蛋白或其活性片斷的第三區域，而且所述第三區域與第一區域或第二區域或兩者可操作地連接。
232.權利要求218的植物，其還包含與該基因融合物可操作連接的種子特異性啟動子。
233.權利要求232的植物，其中啟動子是菜豆蛋白啟動子。
234.權利要求218的植物，其中硫氧還蛋白相關蛋白來源於選自鼠耳芥屬和小麥的植物物種。
235.權利要求218的植物，其中硫氧還蛋白相關蛋白來源於大腸桿菌。
236.權利要求218的植物，其還包含可在植物細胞中有效作為終止區域的核酸，該核酸可操作地與所述基因融合物連接。
237.權利要求218的植物，其中該基因融合物還包含編碼迴避油體表面的接頭胺基酸序列的核酸序列，其中編碼該接頭胺基酸序列的核酸位於編碼油體蛋白的區域和編碼第一硫氧還蛋白相關蛋白的區域之間。
238.權利要求237的植物，其中所述迴避油體表面的接頭胺基酸序列基本上帶負電荷，或具有至少35kd的分子量。
239.權利要求238的植物，其中所述基因融合物還包含編碼能夠被酶或化學物質特異切割的胺基酸序列的接頭核酸序列，其中該接頭序列位於該迴避油體表面的接頭胺基酸序列和編碼第一硫氧還蛋白相關蛋白的區域之間。
240.權利要求218的植物，其中該基因融合物的區域包含多個密碼子，每個密碼子規定一個胺基酸，其中該區域中的至少一個密碼子是從天然密碼子修飾得到的。
241.權利要求240的植物，其中該修飾密碼子與所述天然密碼子規定相同的胺基酸，且該密碼子是根據植物的密碼子偏好修飾的。
242.權利要求240的植物，其中該修飾密碼子與所述天然密碼子規定不同的胺基酸。
243.權利要求218的植物，其中該植物選自鼠耳芥屬和紅花。
244.轉基因植物，其包含核酸構建體，與基因融合物可操作連接的種子特異性啟動子，其中基因融合物包含編碼油體蛋白或其活性片斷的區域和與之可操作連接的編碼第一硫氧還蛋白相關蛋白或其活性片斷的區域，其中包含油質蛋白及硫氧還蛋白相關蛋白的活性的融合蛋白在植物的種子中產生。
245.權利要求244的轉基因植物，其中所述植物選自鼠耳芥屬和紅花。
246.權利要求244的轉基因植物，其中啟動子是菜豆蛋白啟動子。
247.權利要求244的植物的種子。
248.權利要求247的種子，其包含濃度為總細胞種子蛋白質的至少約0.5％的硫氧還蛋白相關蛋白。
249.權利要求247的種子的提取物，其中所述提取物包含硫氧還蛋白相關蛋白的活性。
250.來自權利要求247的種子的油體。
251.從權利要求247的種子產生的油。
252.製備包含硫氧還蛋白相關活性的融合蛋白的方法，該方法包括步驟提供包含核酸構建體的轉基因植物，所述核酸構建體包含可操作地連接基因融合物的種子特異性啟動子，其中基因融合物包含編碼油體蛋白或其活性片斷的區域和與之可操作連接的編碼第一硫氧還蛋白相關蛋白或其活性片斷的區域，該基因融合物編碼包含硫氧還蛋白相關活性的融合蛋白；從該植物獲得種子；和通過從種子中分離油體回收此融合蛋白。
253.權利要求252的方法，其還包括步驟對油體進行分級分離以部分純化所述融合蛋白。
254.通過權利要求252的方法獲得的與融合蛋白結合的油體。
255.權利要求252的方法，其還包括步驟在分級分離油體後將油體蛋白和硫氧還蛋白相關蛋白切開。
256.權利要求255的方法，其中切割步驟包括使用蛋白酶。
257.權利要求255的方法，其中切割步驟包括化學蛋白水解。
258.降低食物的變應原性的方法，包括步驟提供包含與融合蛋白結合的油體的製品，所述融合蛋白包含油體蛋白或其活性片斷及硫氧還蛋白相關蛋白或其活性片斷；和將該製品加入食物中，由此藉助硫氧還蛋白相關蛋白或片斷的活性降低食物的變應原性。
259.權利要求258的方法，其中食物選自小麥麵粉、小麥麵團、奶、乾酪、酸牛奶和冰淇淋。
260.權利要求258的方法，其還包括在實質上缺少NADPH時提供NADH作為輔因子。
261.在可藥用載體中包含融合蛋白的組合物，所述融合蛋白包含油體蛋白或其活性片斷和硫氧還蛋白相關蛋白或其活性片斷。
262.權利要求261的組合物，其還包含與所述融合蛋白結合的油體。
263.在可藥用載體中包含與融合蛋白結合的油體的化妝品製劑，該融合蛋白包含油體蛋白或其活性片斷和硫氧還蛋白相關蛋白或其活性片斷。
264.治療或保護靶對象使其抵抗氧化壓力的方法，其包括步驟提供包含融合蛋白的製品，所述融合蛋白包含油體蛋白或其活性片斷和硫氧還蛋白相關蛋白或其活性片斷；和使該製品和易受氧化壓力影響的靶對象接觸，由此達到抵抗氧化壓力的治療或保護作用。
265.權利要求264的方法，其中所述靶對象選自分子、分子複合物、細胞、組織和器官。
266.包含基因融合物的核酸構建體，其中所述基因構建體包含編碼油體蛋白或其活性片斷的第一區，與第一區可操作連接的編碼至少一個多肽或其活性片斷的第二區，以及於閱讀框中位於第一和第二區多肽之間的迴避油體表面的接頭。
全文摘要
本發明公開了製備與油體結合的多聚體蛋白質複合物，如氧還蛋白和免疫球蛋白的改良方法。與油體結合製備時該氧還蛋白具有酶學活性。本發明還提供相關的核酸、蛋白質、細胞、植物和組合物。
文檔編號A61P11/00GK1486368SQ01822068
公開日2004年3月31日 申請日期2001年12月19日 優先權日2000年12月19日
發明者G·范羅伊珍, H·德克爾斯, P·B·海費茨, S·P·布裡格斯, B·K·道爾米亞, G·戴爾瓦爾, S·薩普拉琴斯基, M·莫洛尼, G 範羅伊珍, 叨, 布裡格斯, 海費茨, 碩, 綻 偎夠, 迥, 道爾米亞 申請人:塞姆柏奧希斯遺傳學公司, 辛根塔參與股份公司