CN108699536A - 具有改进的特性的ω-羟化酶相关的融合多肽变体 - Google Patents

具有改进的特性的ω-羟化酶相关的融合多肽变体 Download PDF

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CN108699536A
CN108699536A CN201680081302.3A CN201680081302A CN108699536A CN 108699536 A CN108699536 A CN 108699536A CN 201680081302 A CN201680081302 A CN 201680081302A CN 108699536 A CN108699536 A CN 108699536A
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cyp153a
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A·席尔默
B·朱
E·波波瓦
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Abstract

本公开涉及ω‑羟化酶相关的融合多肽,所述多肽当在重组宿主细胞中表达时引起改进的ω‑羟基化脂肪酸衍生物产生。本公开进一步涉及用于表达用来产生ω‑羟基化脂肪酸衍生物的ω‑羟化酶相关的融合多肽的微生物。

Description

具有改进的特性的ω-羟化酶相关的融合多肽变体
相关申请的交叉引用
本申请是2015年12月15日提交的国际申请号PCT/EP2015/079832的部分接续案,该案的完整公开内容以引用的方式在此并入。
序列表
本申请含有已经以ASCII格式用电子方式递交并且以整体引用的方式在此并入的序列表。在2016年12月12日创建的所述ASCII拷贝命名为LS00054PCT3_SL.txt并且大小为936,451字节。
领域
本公开涉及ω-羟化酶相关的融合多肽和其变体,所述多肽和其变体当在重组宿主细胞中表达时引起改进的ω-羟基化脂肪酸衍生物产生。本公开进一步涉及用于表达用来产生ω-羟基化脂肪酸衍生物的ω-羟化酶相关的融合多肽和其变体的微生物。
背景
细胞色素P450单加氧酶(P450)是一组多种多样的酶。其被分类为家族和子家族。当其共享大于或等于百分之四十的氨基酸同一性时,其属于同一家族。当其共享大于或等于百分之五十五的氨基酸同一性时,其属于同一子家族。P450使用脂肪酸作为底物并且催化羟基化反应。细菌具有牵涉于烷烃降解和脂肪酸修饰中的数种P450系统并且迄今已知超过1000种微生物P450。一种特定P450子家族被称作cyp153A,其中最初在2001年从乙酸钙不动杆菌(Acinetobacter calcoaceticus)克隆。其后,已经在如鞘氨醇单胞菌属种(Sphingomonas sp.)HXN200、分支杆菌属种(Mycobacterium sp.)HXN1500和博克岛食烷菌(Alcanivorax borkumensis)的其它烷烃利用物种中鉴定出相似的酶(Van Bogaert等人(2011)FEBS Journal 278:206-221)。来自细菌CYP153A子家族的数种P450为具有高末端区域选择性的烷烃ω-羟化酶(ω-羟化酶,还称作ω-加氧酶)。CYP153A也已经与工业上相关的ω-羟基化(ω-羟基化)脂肪族化合物的合成相关,所述脂肪族化合物如伯醇、ω-羟基化脂肪酸和双官能脂肪酸衍生物(如α,ω-二羧酸和α,ω-二醇)(Honda Malca等人(2012)Chem.Commun.48:5115-5117)。
概述
本公开提供可在宿主细胞中产生ω-羟基化-和双官能脂肪酸衍生物的ω-羟化酶相关的融合多肽和其变体。更具体说来,本公开提供CYP153A-还原酶杂合融合多肽变体,所述变体产生ω-羟基化-(ω-羟基化)和双官能脂肪酸衍生物和其组合物,包括ω-羟基化脂肪酸、ω-羟基化脂肪酯、α,ω-二酸、α,ω-二酯、α,ω-二醇和由其衍生的化学品(如大环内酯)。还提供特异性CYP153A-还原酶杂合融合核酸和蛋白质序列以及包含此类工程改造的CYP153A-还原酶杂合融合多肽变体的重组宿主细胞和细胞培养物。本公开还提供使用表达重组CYP153A-还原酶杂合融合多肽变体的宿主细胞以便制备ω-羟基化和/或双官能脂肪酸衍生物或其组合物的方法。
本公开的一方面提供催化脂肪酸转化为ω-羟基化(ω-OH)脂肪酸或脂肪酸衍生物的CYP153A-还原酶杂合融合多肽变体,其中所述CYP153A-还原酶杂合融合多肽变体与CYP153A-还原酶杂合融合多肽序列SEQ ID NO:38具有至少约80%、81%、82%、83%、84%、85%、86%、87%、88%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或100%序列同一性。进一步包括用于表达CYP153A-还原酶杂合融合多肽和其变体的方法。一方面,所述CYP153A-还原酶杂合融合多肽变体与SEQ ID NO:38具有至少80%、81%、82%、83%、84%、85%、86%、87%、88%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或100%序列同一性并且如与由野生型CYP153A的表达或CYP153A-还原酶杂合融合多肽SEQ ID NO:6或SEQ ID NO:38的表达产生的效价相比,所述CYP153A-还原酶杂合融合多肽变体在重组宿主细胞中的表达引起ω-OH脂肪酸或脂肪酸衍生物或其组合物的更高效价。一方面,所述重组宿主细胞当在含有碳源的培养基中在有效表达所述CYP153A-还原酶杂合融合多肽变体的条件下培养时产生ω-OH脂肪酸或ω-OH脂肪酸衍生物或其组合物,其具有比由表达相应野生型CYP153A或表达CYP153A-还原酶杂合融合多肽SEQ ID NO:6或SEQ ID NO:38的宿主细胞产生的ω-OH脂肪酸或ω-OH脂肪酸衍生物或其组合物的效价大至少约1%、2%、3%、4%、5%、6%、7%、8%、9%、10%、11%、12%、13%、14%、15%、16%、17%、18%、19%或20%的效价。另一方面,所述ω-OH脂肪酸或ω-OH脂肪酸衍生物或其组合物在细胞外产生。
一方面,本公开提供一种CYP153A-还原酶杂合融合多肽变体,其包含与氨基酸序列SEQ ID NO:38的至少80%或至少90%序列同一性,其中所述CYP153A-还原酶杂合融合多肽变体包含在氨基酸位置12处的突变和在以下氨基酸位置中的每一者处的突变:(a)SEQID NO:38的27、119、140、157、159、233和244;(b)SEQ ID NO:38的28、61、119、231、309、413和480;(c)SEQ ID NO:38的119、231和480;(d)SEQ ID NO:38的28、77、119、141、231和407;(e)SEQ ID NO:38的28、61、141、231和407;(f)SEQ ID NO:38的28、119、231和244;(g)SEQID NO:38的28、407和480;(h)SEQ ID NO:38的141、231、413和481;(i)SEQ ID NO:38的28、111、231和407;(j)SEQ ID NO:38的28、61、140和149;(k)SEQ ID NO:38的28、77、119、159、231、254、407和480;(l)SEQ ID NO:38的28、254、309、407和451;(m)SEQ ID NO:38的28、254、309、407和480;或(n)SEQ ID NO:38的28、309、407、451和480;其中所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-羟基化脂肪酸。在多个实施方案中,在(a)氨基酸位置SEQ ID NO:38的12、27、119、140、157、159、233和244处的所述突变为氨基酸取代。在多个实施方案中,在(b)氨基酸位置SEQ ID NO:38的12、28、61、119、231、309、413和480处的所述突变为氨基酸取代。在多个实施方案中,在(c)氨基酸位置SEQ ID NO:38的12、119、231和480处的所述突变为氨基酸取代。在多个实施方案中,在(d)氨基酸位置SEQ ID NO:38的12、28、77、119;141、231和407处的所述突变为氨基酸取代。在多个实施方案中,在(e)氨基酸位置SEQ ID NO:38的12、28、61、141、231和407处的所述突变为氨基酸取代。在多个实施方案中,在(f)氨基酸位置SEQ ID NO:38的12、28、119、231和244处的所述突变为氨基酸取代。在多个实施方案中,在(g)氨基酸位置SEQ ID NO:38的12、28、407和480处的所述突变为氨基酸取代。在多个实施方案中,在(h)氨基酸位置SEQ ID NO:38的12、141、231、413和481处的所述突变为氨基酸取代。在多个实施方案中,在(i)氨基酸位置SEQ ID NO:38的12、28、111、231和407处的所述突变为氨基酸取代。在多个实施方案中,在(j)氨基酸位置SEQ IDNO:38的12、28、61、140和149处的所述突变为氨基酸取代。在多个实施方案中,在(k)氨基酸位置12、28、77、119、159、231、254、407和480处的所述突变为氨基酸取代。在多个实施方案中,在(l)氨基酸位置SEQ ID NO:38的12、28、254、309、407和451处的所述突变为氨基酸取代。在多个实施方案中,在(m)氨基酸位置SEQ ID NO:38的12、28、254、309、407和480处的所述突变为氨基酸取代。在多个实施方案中,在(n)氨基酸位置SEQ ID NO:38的12、28、309、407、451和480处的所述突变为氨基酸取代。在一个实施方案中,在(a)氨基酸位置SEQ IDNO:38的12、27、119、140、157、159、233和244处的所述突变分别为Q12W、R27L、K119R、S140N、S157R、V159M、S233L和A244R。在一个实施方案中,在(b)氨基酸位置SEQ ID NO:38的12、28、61、119、231、309、413和480处的所述突变分别为Q12R、Q28M、N61L、K119R、A231V、N309S、Y413R和I480G。在一个实施方案中,在(c)氨基酸位置SEQ ID NO:38的12、119、231和480处的所述突变分别为Q12R、K119R、A231V和I480G。在一个实施方案中,在(d)氨基酸位置SEQID NO:38的12、28、77、119;141、231和407处的所述突变分别为Q12T、Q28M、R77Q、K119R、V141T、A231W和N407G。在一个实施方案中,在(e)氨基酸位置SEQ ID NO:38的12、28、61、141、231和407处的所述突变分别为Q12R、Q28M、N61L、V141T、A231Y和N407G。在一个实施方案中,在(f)氨基酸位置SEQ ID NO:38的12、28、119、231和244处的所述突变分别为Q12W、Q28M、K119R、A231Y和A244R。在一个实施方案中,在(g)氨基酸位置SEQ ID NO:38的12、28、407和480处的所述突变分别为Q12W、Q28T、N407G和I480G。在一个实施方案中,在(h)氨基酸位置SEQ ID NO:38的12、141、231、413和481处的所述突变分别为Q12R、V141T、A231Y、Y413R和G481I。在一个实施方案中,在(i)氨基酸位置SEQ ID NO:38的12、28、111、231和407处的所述突变分别为Q12T、Q28M、F111A、A231V和N407G。在一个实施方案中,在(j)氨基酸位置SEQ ID NO:38的12、28、61、140和149处的所述突变分别为Q12T、Q28M、N61L、S140N和P149R。在一个实施方案中,在(k)氨基酸位置12、28、77、119、159、231、254、407和480处的所述突变分别为Q12W、Q28T、R77Q、K119R、V159M、A231Y、R254G、N407G和I480G。在一个实施方案中,在(l)氨基酸位置SEQ ID NO:38的12、28、254、309、407和451处的所述突变分别为Q12W、Q28T、R254G、N309S、N407G和V451M。在一个实施方案中,在(m)氨基酸位置SEQ ID NO:38的12、28、254、309、407和480处的所述突变分别为Q12W、Q28T、R254G、N309S、N407G和I480G。在一个实施方案中,在(n)氨基酸位置SEQ ID NO:38的12、28、309、407、451和480处的所述突变分别为Q12W、Q28T、N309S、N407G、V451M和I480G。在一个优选实施方案中,以上(a)的CYP153A-还原酶杂合融合多肽变体进一步包含在氨基酸位置SEQ ID NO:38的141、231和407中的每一者处,或在氨基酸位置SEQ ID NO:38的231、407、451、757、770和784中的每一者处,或在氨基酸位置SEQ ID NO:38的231、407、591、643、757和784中的每一者处的突变。在多个实施方案中,在氨基酸位置SEQ ID NO:38的141、231和407中的每一者处的所述进一步突变为氨基酸取代。另外,在多个实施方案中,在氨基酸位置SEQ ID NO:38的231、407、451、757、770和784中的每一者处的所述进一步突变为氨基酸取代。另外,在多个实施方案中,在氨基酸位置SEQ ID NO:38的231、407、591、643、757和784中的每一者处的所述进一步突变为氨基酸取代。优选地,在氨基酸位置SEQ ID NO:38的141、231和407中的每一者处的所述进一步突变分别为V141T、A231Y和N407G。另外,优选地,在氨基酸位置SEQ ID NO:38的231、407、451、757、770和784中的每一者处的所述突变分别为A231Y、N407G、V451M、E757A、T770G和M784I。另外,优选地,在氨基酸位置SEQ ID NO:38的231、407、591、643、757和784中的每一者处的所述突变分别为A231Y、N407G、E591Q、R643H、E757A和M784I。更优选地,本公开的CYP153A-还原酶杂合融合多肽变体包含氨基酸序列SEQ ID NO:146、SEQ ID NO:150或SEQ ID NO:160。在本公开的其它实施方案中,所述CYP153A-还原酶杂合融合多肽变体包含氨基酸序列SEQ ID NO:98、SEQ ID NO:100、SEQ ID NO:102、SEQ ID NO:104、SEQ ID NO:106、SEQ IDNO:108、SEQ ID NO:110、SEQ ID NO:112、SEQ ID NO:114、SEQ ID NO:116、SEQ ID NO:118、SEQ ID NO:120、SEQ ID NO:122和SEQ ID NO:124中的任一者。
另一方面,本公开提供一种CYP153A-还原酶杂合融合多肽变体,其包含与氨基酸序列SEQ ID NO:38的至少80%或至少90%序列同一性,其中所述CYP153A-还原酶杂合融合多肽变体包含在RhF结构域(或RhF还原酶结构域,或Red450RhF结构域,或Red450RhF还原酶结构域,或P450RhF结构域,或P450RhF还原酶结构域)中在以下氨基酸位置中的每一者处的突变:(a)SEQ ID NO:38的527、544、719、757、771和784;(b)SEQ ID NO:38的527、544和557;(c)SEQ ID NO:38的770和784;(d)SEQ ID NO:38的527、591、648、719、757、771和784;(e)SEQ ID NO:38的527、591、648、757和771;(f)SEQ ID NO:38的527、544、770和784;(g)SEQID NO:38的527、557、770和784;(h)SEQ ID NO:38的557、757和770;(i)SEQ ID NO:38的557、757和771;或(j)SEQ ID NO:38的757和770;其中所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-羟基化脂肪酸。在多个实施方案中,在(a)氨基酸位置SEQ ID NO:38的527、544、719、757、771和784处的所述突变为氨基酸取代。在多个实施方案中,在(b)氨基酸位置SEQ ID NO:38的527、544和557处的所述突变为氨基酸取代。在多个实施方案中,在(c)氨基酸位置SEQ ID NO:38的770和784处的所述突变为氨基酸取代。在多个实施方案中,在(d)氨基酸位置SEQ ID NO:38的527、591、648、719、757、771和784处的所述突变为氨基酸取代。在多个实施方案中,在(e)氨基酸位置SEQ ID NO:38的527、591、648、757和771处的所述突变为氨基酸取代。在多个实施方案中,在(f)氨基酸位置SEQ ID NO:38的527、544、770和784处的所述突变为氨基酸取代。在多个实施方案中,在(g)氨基酸位置SEQ ID NO:38的527、557、770和784处的所述突变为氨基酸取代。在多个实施方案中,在(h)氨基酸位置SEQ ID NO:38的557、757和770处的所述突变为氨基酸取代。在多个实施方案中,在(i)氨基酸位置SEQ ID NO:38的557、757和771处的所述突变为氨基酸取代。在多个实施方案中,在(j)氨基酸位置SEQ ID NO:38的757和770处的所述突变为氨基酸取代。在一个实施方案中,在(a)氨基酸位置SEQ ID NO:38的527、544、719、757、771和784处的所述突变分别为D527E、D544N、R719W、E757A、V771F和M784I。在一个实施方案中,在(b)氨基酸位置SEQ ID NO:38的527、544和557处的所述突变分别为D527E、D544N和E557R。在一个实施方案中,在(c)氨基酸位置SEQ ID NO:38的770和784处的所述突变分别为T770G和M784I。在一个实施方案中,在(d)氨基酸位置SEQ ID NO:38的527、591、648、719、757、771和784处的所述突变分别为D527E、E591Q、V648L、R719W、E757A、V771F和M784I。在一个实施方案中,在(e)氨基酸位置SEQ ID NO:38的527、591、648、757和771处的所述突变分别为D527E、E591Q、V648L、E757A和V771F。在一个实施方案中,在(f)氨基酸位置SEQ ID NO:38的527、544、770和784处的所述突变分别为D527E、D544N、T770G和M784I。在一个实施方案中,在(g)氨基酸位置SEQ ID NO:38的527、557、770和784处的所述突变分别为D527E、E557R、T770G和M784I。在一个实施方案中,在(h)氨基酸位置SEQ ID NO:38的557、757和770处的所述突变分别为E557W、E757A和T770G。在一个实施方案中,在(i)氨基酸位置SEQ ID NO:38的557、757和771处的所述突变分别为E557R、E757A和V771F。在一个实施方案中,在(j)氨基酸位置SEQ ID NO:38的757和770处的所述突变分别为E757A和T770G。在本公开的一些优选实施方案中,所述CYP153A-还原酶杂合融合多肽变体包含氨基酸序列SEQ ID NO:126、SEQ ID NO:128、SEQ ID NO:130、SEQ ID NO:132、SEQ ID NO:134、SEQ ID NO:136、SEQ ID NO:138、SEQ ID NO:140、SEQ IDNO:142和SEQ ID NO:144中的任一者。
另一方面,本公开提供一种CYP153A-还原酶杂合融合多肽变体,其包含与氨基酸序列SEQ ID NO:38的至少80%或至少90%序列同一性,其中所述CYP153A-还原酶杂合融合多肽变体包含在以下位置中的每一者处的突变:(a)SEQ ID NO:38的141、231、233和254;(b)SEQ ID NO:38的141、231、233和244;(c)SEQ ID NO:38的141、231、244、451、557、749和770;(d)SEQ ID NO:38的27、28、61、141、149和231;(e)SEQ ID NO:38的141、157、231、233、244、757和784;(f)SEQ ID NO:38的28、61、140、141、231、233和271;或(g)SEQ ID NO:38的231、233、254和557;其中所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-羟基化脂肪酸。在多个实施方案中,在(a)氨基酸位置SEQ ID NO:38的141、231、233和254处的所述突变为氨基酸取代。在多个实施方案中,在(b)氨基酸位置SEQ ID NO:38的141、231、233和244处的所述突变为氨基酸取代。在多个实施方案中,在(c)氨基酸位置SEQ ID NO:38的141、231、244、451;557、749和770处的所述突变为氨基酸取代。在多个实施方案中,在(d)氨基酸位置SEQ ID NO:38的27、28、61、141、149和231处的所述突变为氨基酸取代。在多个实施方案中,在(e)氨基酸位置SEQ ID NO:38的141、157、231、233、244、757和784处的所述突变为氨基酸取代。在多个实施方案中,在(f)氨基酸位置SEQ ID NO:38的28、61、140、141、231、233和271处的所述突变为氨基酸取代。在多个实施方案中,在(g)氨基酸位置SEQ IDNO:38的231、233、254和557处的所述突变为氨基酸取代。在一个实施方案中,在(a)氨基酸位置SEQ ID NO:38的141、231、233和254处的所述突变分别为V141T、A231Y、L233S和R254G。在一个实施方案中,在(b)氨基酸位置SEQ ID NO:38的141、231、233和244处的所述突变分别为V141T、A231Y、L233S和R244A。在一个实施方案中,在(c)氨基酸位置SEQ ID NO:38的141、231、244、451、557、749和770处的所述突变分别为V141T、A231Y、R244A、V451M、E557W、E749L和T770G。在一个实施方案中,在(d)氨基酸位置SEQ ID NO:38的27、28、61、141、149和231处的所述突变分别为L27R、Q28M、N61L、V141T、P149G和A231Y。在一个实施方案中,在(e)氨基酸位置SEQ ID NO:38的141、157、231、233、244、757和784处的所述突变分别为V141T、R157S、A231Y、L233S、R244A、E757A和M784I。在一个实施方案中,在(f)氨基酸位置SEQ IDNO:38的28、61、140、141、231、233和271处的所述突变分别为Q28M、N61L、N140S、V141T、A231Y、L233S和E271D。在一个实施方案中,在(g)氨基酸位置SEQ ID NO:38的231、233、254和557处的所述突变分别为A231Y、L233S、R254G和E557W。在本公开的一些优选实施方案中,本公开的CYP153A-还原酶杂合融合多肽变体包含氨基酸序列SEQ ID NO:148、SEQ ID NO:152、SEQ ID NO:154、SEQ ID NO:156、SEQ ID NO:158、SEQ ID NO:162和SEQ ID NO:164中的任一者。
另一方面,本公开提供一种CYP153A-还原酶杂合融合多肽变体,其包含与氨基酸序列SEQ ID NO:98的至少80%或至少90%序列同一性,其中所述CYP153A-还原酶杂合融合多肽变体包含在以下位置中的每一者处的突变:(a)SEQ ID NO:98的141、231和407;(b)SEQID NO:98的141、231、233和254;(c)SEQ ID NO:98的231、407、451、757、770和784;(d)SEQID NO:98的141、231、233和244;(e)SEQ ID NO:98的141、231、244、451、557、749和770;(f)SEQ ID NO:98的27、28、61、141、149和231;(g)SEQ ID NO:98的27、119、140、141、159、231、757和784;(h)SEQ ID NO:98的231、407、591、643、757和784;(i)SEQ ID NO:98的28、61、140、141、231、233和271;或(j)SEQ ID NO:98的231、233和254;其中所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-羟基化脂肪酸。在多个实施方案中,在(a)氨基酸位置SEQ ID NO:98的141、231和407处的所述突变为氨基酸取代。在多个实施方案中,在(b)氨基酸位置SEQ ID NO:98的141、231、233和254处的所述突变为氨基酸取代。在多个实施方案中,在(c)氨基酸位置SEQ ID NO:98的231、407、451、757、770和784处的所述突变为氨基酸取代。在多个实施方案中,在(d)氨基酸位置SEQ ID NO:98的141、231、233和244处的所述突变为氨基酸取代。在多个实施方案中,在(e)氨基酸位置SEQ ID NO:98的141、231、244、451、557、749和770处的所述突变为氨基酸取代。在多个实施方案中,在(f)氨基酸位置SEQ IDNO:98的27、28、61、141、149和231处的所述突变为氨基酸取代。在多个实施方案中,在(g)氨基酸位置SEQ ID NO:98的27、119、140、141、159、231、757和784处的所述突变为氨基酸取代。在多个实施方案中,在(h)氨基酸位置SEQ ID NO:98的231、407、591、643、757和784处的所述突变为氨基酸取代。在多个实施方案中,在(i)氨基酸位置SEQ ID NO:98的28、61、140、141、231、233和271处的所述突变为氨基酸取代。在多个实施方案中,在(j)氨基酸位置SEQID NO:38的231、233和254处的所述突变为氨基酸取代。在一个实施方案中,在(a)氨基酸位置SEQ ID NO:98的141、231和407处的所述突变分别为V141T、A231Y和N407G。在一个实施方案中,在(b)氨基酸位置SEQ ID NO:98的141、231、233和254处的所述突变分别为V141T、A231Y、L233S和R254G。在一个实施方案中,在(c)氨基酸位置SEQ ID NO:98的231、407、451、757、770和784处的所述突变分别为A231Y、N407G、V451M、E757A、T770G和M784I。在一个实施方案中,在(d)氨基酸位置SEQ ID NO:98的141、231、233和244处的所述突变分别为V141T、A231Y、L233S和R244A。在一个实施方案中,在(e)氨基酸位置SEQ ID NO:98的141、231、244、451、557、749和770处的所述突变分别为V141T、A231Y、R244A、V451M、E557W、E749L和T770G。在一个实施方案中,在(f)氨基酸位置SEQ ID NO:98的27、28、61、141、149和231处的所述突变分别为L27R、Q28M、N61L、V141T、P149G和A231Y。在一个实施方案中,在(g)氨基酸位置SEQID NO:98的141、157、231、233、244、757和784处的所述突变分别为V141T、R157S、A231Y、L233S、R244A、E757A和M784I。在一个实施方案中,在(h)氨基酸位置SEQ ID NO:98的231、407、591、643、757和784处的所述突变分别为A231Y、N407G、E591Q、R643H、E757A和M784I。在一个实施方案中,在(i)氨基酸位置SEQ ID NO:98的28、61、140、141、231、233和271处的所述突变分别为Q28M、N61L、N140S、V141T、A231Y、L233S和E271D。在一个实施方案中,在(j)氨基酸位置SEQ ID NO:98的231、233、254和557处的所述突变分别为A231Y、L233S、R254G和E557W。在本公开的一些优选实施方案中,本公开的CYP153A-还原酶杂合融合多肽变体包含氨基酸序列SEQ ID NO:146、SEQ ID NO:148、SEQ ID NO:150、SEQ ID NO:152、SEQ ID NO:154、SEQ ID NO:156、SEQ ID NO:158、SEQ ID NO:160;SEQ ID NO:162和SEQ ID NO:164中的任一者。
在本公开的多个实施方案中,如与通过例如CYP153A-还原酶杂合融合多肽SEQ IDNO:6或SEQ ID NO:38在相应宿主细胞中的表达产生的ω-羟基化脂肪酸的效价相比,由本公开提供的CYP153A-还原酶杂合融合多肽变体在重组宿主细胞中的表达引起ω-羟基化脂肪酸的较高效价。此外,在本公开的多个实施方案中,由本公开提供的CYP153A-还原酶杂合融合多肽变体为杂合CYP153A-RedRhF融合蛋白变体。
一方面,本公开提供一种表达由本公开提供的CYP153A-还原酶杂合融合多肽变体的重组宿主细胞。在多个实施方案中,所述重组宿主细胞进一步表达EC 3.1.2.-、EC3.1.1.5或EC 3.1.2.14的硫酯酶多肽。另外,在多个实施方案中,当在含有碳源的培养基中培养时,所述重组宿主细胞产生ω-羟基化脂肪酸组合物,其具有比由表达包含SEQ ID NO:38或SEQ ID NO:6的相应CYP153A-还原酶杂合融合多肽的宿主细胞产生的ω-羟基化脂肪酸组合物的效价大至少10%、大至少15%、大至少20%、大至少25%或大至少30%的效价。
另一方面,本公开提供一种包含本公开的重组宿主细胞的细胞培养物。
另一方面,本公开提供一种产生ω-羟基化脂肪酸的方法,所述方法包括:(i)在碳源存在下培养本公开的重组宿主细胞或本公开的细胞培养物;和(ii)收集ω-羟基化脂肪酸。
另一方面,本公开提供一种重组微生物,其包含经过工程改造以表达编码多肽的至少两个核酸序列的路径,所述多肽包含:(i)EC3.1.2.-、EC 3.1.1.5或EC 3.1.2.14的硫酯酶;和(ii)本公开的CYP153A-还原酶杂合融合多肽变体。
在本公开的多个实施方案中,所述CYP153A-还原酶杂合融合多肽变体为自给自足的CYP153A-RedRhF杂合融合蛋白变体。
本公开的另一方面提供一种CYP153A-还原酶杂合融合多肽变体,其与SEQ ID NO:6具有至少约90%、91%、93%、94%、95%、96%、97%、98%或99%序列同一性并且在包括位置796、141、231、27、82、178、309、407、415、516和/或666的氨基酸位置处具有至少一个突变,其中所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-OH脂肪酸。所述CYP153A-还原酶杂合融合多肽变体在以下位置中的任一处或多处具有突变,包括位置A796V,其中丙氨酸(A)被缬氨酸(V)取代(即,置换);位置V141I,其中缬氨酸被异亮氨酸(I)取代;位置V141Q,其中缬氨酸(V)被谷氨酰胺(Q)取代;位置V141G,其中缬氨酸(V)被甘氨酸(G)取代;位置V141M,其中缬氨酸(V)被甲硫氨酸(M)取代;位置V141L,其中缬氨酸(V)被亮氨酸(L)取代;位置V141T,其中缬氨酸(V)被苏氨酸(T)取代;位置A231T,其中丙氨酸(A)被苏氨酸(T)取代;位置R27L,其中精氨酸(R)被赖氨酸(L)取代;位置R82D,其中精氨酸(R)被天冬氨酸(D)取代;位置R178N,其中精氨酸(R)被天冬酰胺(N)取代;位置N309R,其中天冬酰胺(N)被精氨酸(R)取代;位置N407A,其中天冬酰胺(N)被丙氨酸(A)取代;位置V415R,其中缬氨酸(V)被精氨酸(R)取代;位置T516V,其中苏氨酸(T)被缬氨酸(V)取代;位置P666A,其中脯氨酸(P)被丙氨酸(A)取代;和位置P666D,其中脯氨酸(P)被天冬氨酸(D)取代。CYP153A-还原酶杂合融合多肽变体的实例包括SEQ ID NO:8、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:14、SEQ ID NO:16、SEQ ID NO:18、SEQ ID NO:20、SEQ ID NO:22、SEQ IDNO:24、SEQ ID NO:26、SEQ ID NO:28或SEQ ID NO:30、SEQ ID NO:32、SEQ ID NO:34、SEQID NO:36、SEQ ID NO:38、SEQ ID NO:40、SEQ ID NO:42、SEQ ID NO:44和SEQ ID NO:46,如序列表A所示(段落[0146])。在一个实施方案中,所述CYP153A-还原酶杂合融合多肽变体为杂合CYP153A-RedRhF型融合蛋白变体。在另一实施方案中,如与由CYP153A-还原酶杂合融合多肽(模板;例如,SEQ ID NO:6、SEQ ID NO:38、SEQ ID NO:98)在相应宿主细胞中的表达产生的ω-OH脂肪酸或ω-OH脂肪酸衍生物或其组合物的效价相比,在重组宿主细胞中的所述CYP153A-还原酶杂合融合多肽变体引起ω-OH脂肪酸或ω-OH脂肪酸衍生物或其组合物的更高效价。在另一实施方案中,所述CYP153A-还原酶杂合融合多肽变体在氨基酸位置796处具有突变,包括A796V。在另一实施方案中,所述CYP153A-还原酶杂合融合多肽变体在氨基酸位置231处具有突变,包括A231T。在另一实施方案中,所述CYP153A-还原酶杂合融合多肽变体在氨基酸位置141处具有突变,包括V141I或V141T。本文中,如与由CYP153A-还原酶杂合融合多肽(模板;例如,SEQ ID NO:6、SEQ ID NO:38、SEQ ID NO:98)的表达产生的ω-OH C12或C16脂肪酸的效价相比,具有突变A796V、V141I或V141T和/或A231T的CYP153A-还原酶杂合融合多肽变体在重组宿主细胞中的表达分别引起ω-OH C12或C16脂肪酸的更高效价。
本公开进一步涵盖具有表达如由本公开提供的CYP153A-还原酶杂合融合多肽变体的重组宿主细胞的细胞培养物。ω-OH脂肪酸或脂肪酸衍生物或其组合物可包括C6、C7、C8、C9、C10、C11、C12、C13、C14、C15、C16、C17、C18、C19和C20ω-OH脂肪酸或脂肪酸衍生物中的一者或多者。ω-OH脂肪酸或脂肪酸衍生物或其组合物可包括饱和或不饱和ω-OH脂肪酸或脂肪酸衍生物。在另一实施方案中,ω-OH脂肪酸或脂肪酸衍生物或其组合物可包括C8:1、C9:1、C10:1、C11:1、C12:1、C13:1、C14:1、C15:1、C16:1、C17:1、C18:1、C19:1和C20:1不饱和ω-OH脂肪酸或脂肪酸衍生物中的一者或多者。在另一实施方案中,ω-OH脂肪酸或脂肪酸衍生物或其组合物可包括ω-OH C12和/或C16和/或C16:1脂肪酸或脂肪酸衍生物。
本公开的另一方面提供一种产生ω-OH脂肪酸或脂肪酸衍生物或其组合物的方法,所述方法包括用碳源培养表达本公考的CYP153A-还原酶杂合融合多肽变体的宿主细胞;和收集ω-OH脂肪酸或ω-OH脂肪酸衍生物。所述方法提供ω-OH脂肪酸或ω-OH脂肪酸衍生物或其组合物的效价的增加/改进。一方面,ω-OH脂肪酸或脂肪酸衍生物比由表达CYP153A-还原酶杂合融合多肽的宿主细胞、特别是由表达例如SEQ ID NO:6、SEQ ID NO:38或SEQ ID NO:98的CYP153A-还原酶杂合融合多肽的宿主细胞产生的ω-OH脂肪酸或脂肪酸衍生物的效价大至少约20%至30%。另一方面,ω-OH脂肪酸或脂肪酸衍生物或其组合物以约15g/L至约25g/L的效价从碳源、特别是来自可再生原料的碳源产生。在多个实施方案中,所述基于碳的可再生原料是选自由玉米、甘蔗、高粱、甜菜、柳枝稷、青贮饲料、稻草、木材、纸浆、污水、垃圾、纤维素城市废物、烟道气、合成气、生物质水解液和二氧化碳组成的组。
本公开的另一方面提供在V141I和A231T处具有突变的与SEQ ID NO:32具有至少约90%、91%、93%、94%、95%、96%、97%、98%、99%或100%序列同一性的CYP153A-还原酶杂合融合多肽变体,其中所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-OH C6、C7、C8、C9、C10、C11、C12、C13、C14、C15、C16、C17、C18、C19、C20、C8:1、C9:1、C10:1、C11:1、C12:1、C13:1、C14:1、C15:1、C16:1、C17:1、C18:1、C19:1和/或C20:1脂肪酸或脂肪酸衍生物或其组合物。本公开的另一方面提供在R27L、R82D、V141M、R178N和N407A处具有突变的与SEQ ID NO:34具有至少约90%、91%、93%、94%、95%、96%、97%、98%、99%或100%序列同一性的CYP153A-还原酶杂合融合多肽变体,其中所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-OHC6、C7、C8、C9、C10、C11、C12、C13、C14、C15、C16、C17、C18、C19、C20、C8:1、C9:1、C10:1、C11:1、C12:1、C13:1、C14:1、C15:1、C16:1、C17:1、C18:1、C19:1和/或C20:1脂肪酸或脂肪酸衍生物或其组合物。本公开的另一方面提供在P666A处具有突变的与SEQ ID NO:36具有至少约90%、91%、93%、94%、95%、96%、97%、98%、99%或100%序列同一性的CYP153A-还原酶杂合融合多肽变体,其中所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-OH C6、C7、C8、C9、C10、C11、C12、C13、C14、C15、C16、C17、C18、C19、C20、C8:1、C9:1、C10:1、C11:1、C12:1、C13:1、C14:1、C15:1、C16:1、C17:1、C18:1、C19:1和/或C20:1脂肪酸或脂肪酸衍生物或其组合物。本公开的另一方面提供在A796V处具有突变的与SEQ ID NO:38具有至少约90%、91%、93%、94%、95%、96%、97%、98%、99%或100%序列同一性的CYP153A-还原酶杂合融合多肽变体,其中所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-OH C6、C7、C8、C9、C10、C11、C12、C13、C14、C15、C16、C17、C18、C19、C20、C8:1、C9:1、C10:1、C11:1、C12:1、C13:1、C14:1、C15:1、C16:1、C17:1、C18:1、C19:1和/或C20:1脂肪酸或脂肪酸衍生物或其组合物。本公开的另一方面提供在A796V、P666D和T516V处具有突变的与SEQ ID NO:40具有至少约90%、91%、93%、94%、95%、96%、97%、98%、99%或100%序列同一性的CYP153A-还原酶杂合融合多肽变体,其中所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-OH C6、C7、C8、C9、C10、C11、C12、C13、C14、C15、C16、C17、C18、C19、C20、C8:1、C9:1、C10:1、C11:1、C12:1、C13:1、C14:1、C15:1、C16:1、C17:1、C18:1、C19:1和/或C20:1脂肪酸或脂肪酸衍生物或其组合物。本公开的另一方面提供在V141I、A231T和A796V处具有突变的与SEQ ID NO:42具有至少约90%、91%、93%、94%、95%、96%、97%、98%、99%或100%序列同一性的CYP153A-还原酶杂合融合多肽变体,其中所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-OH C6、C7、C8、C9、C10、C11、C12、C13、C14、C15、C16、C17、C18、C19、C20、C8:1、C9:1、C10:1、C11:1、C12:1、C13:1、C14:1、C15:1、C16:1、C17:1、C18:1、C19:1和/或C20:1脂肪酸或脂肪酸衍生物或其组合物。本公开的另一方面提供在R27L、R82D、V141M、R178N、N407A和A796V处具有突变的与SEQ ID NO:44具有至少约90%、91%、93%、94%、95%、96%、97%、98%、99%或100%序列同一性的CYP153A-还原酶杂合融合多肽变体,其中所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-OH C6、C7、C8、C9、C10、C11、C12、C13、C14、C15、C16、C17、C18、C19、C20、C8:1、C9:1、C10:1、C11:1、C12:1、C13:1、C14:1、C15:1、C16:1、C17:1、C18:1、C19:1和/或C20:1脂肪酸或脂肪酸衍生物或其组合物。本公开的另一方面提供在V141T、A231T和A796V处具有突变的与SEQ ID NO:46具有至少约90%、91%、93%、94%、95%、96%、97%、98%、99%或100%序列同一性的CYP153A-还原酶杂合融合多肽变体,其中所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-OH C6、C7、C8、C9、C10、C11、C12、C13、C14、C15、C16、C17、C18、C19、C20、C8:1、C9:1、C10:1、C11:1、C12:1、C13:1、C14:1、C15:1、C16:1、C17:1、C18:1、C19:1和/或C20:1脂肪酸或脂肪酸衍生物或其组合物。
本公开进一步涵盖表达由本公开提供的CYP153A-还原酶杂合融合多肽变体的重组宿主细胞。在一个实施方案中,所述重组宿主细胞当在含有碳源的培养基中在有效表达本公开的CYP153A-还原酶杂合融合多肽变体的条件下培养时表达本公开的CYP153A-还原酶杂合融合多肽变体和EC 3.1.2.-或EC 3.1.1.5或EC 3.1.2.14的硫酯酶多肽,其中所述重组宿主细胞产生ω-OH脂肪酸或其组合物,其具有比由表达相应CYP153A-还原酶杂合融合多肽,例如表达CYP153A-还原酶杂合融合多肽SEQ ID NO:6或SEQ ID NO:38的宿主细胞产生的ω-OH脂肪酸或其组合物的效价大至少10%、大至少15%、大至少20%、大至少25%或大至少30%的效价。在一个实施方案中,ω-OH脂肪酸或其组合物可以约15g/L至约25g/L的效价产生。在另一实施方案中,ω-OH脂肪酸或其组合物在细胞外产生。
一方面,本公开提供一种重组微生物,其经过工程改造以表达本公开的CYP153A-还原酶杂合融合多肽变体。在多个实施方案中,所述重组微生物产生或能够产生ω-羟基脂肪酸或ω-OH脂肪酸衍生物,具体说来ω-羟基脂肪酸甲酯。在多个实施方案中,所述重组微生物经过工程改造以进一步表达编码多肽的核酸序列,所述多肽包含EC1.1.1.1/2的醇脱氢酶或EC 1.1.3.13或EC 1.1.3.20的醇氧化酶,优选地其中所述重组微生物产生选自由ω-氧代脂肪酸和ω-氧代脂肪酸甲酯组成的组的ω-羟基脂肪酸衍生物。这种重组微生物可经过工程改造以进一步表达编码多肽的核酸序列,所述多肽包含EC 1.2.1.3/4/5的醛脱氢酶或EC 1.2.3.1的醛氧化酶,其中所述重组微生物产生ω-羟基脂肪酸衍生物,所述ω-羟基脂肪酸衍生物为α,ω-二酸或ω-羧基脂肪酸甲酯。这种重组微生物可经过工程改造以进一步表达编码多肽的核酸序列,所述多肽包含EC 6.2.1.3的酰基-CoA连接酶或EC2.8.3.6的酰基-CoA转移酶,其中所述重组微生物产生ω-羟基脂肪酸衍生物,所述ω-羟基脂肪酸衍生物为α,ω-二酯。在多个实施方案中,上文所提及的重组微生物(其经过工程改造以进一步表达编码多肽的核酸序列,所述多肽包含EC 1.1.1.1/2的醇脱氢酶或EC1.1.3.13或EC 1.1.3.20的醇氧化酶)可经过工程改造以进一步表达编码多肽的核酸序列,所述多肽包含EC 2.6.1的氨基转移酶或EC 1.4.9、EC 1.4.98或EC 1.4.99的胺脱氢酶以产生选自由ω-氨基脂肪酸和ω-氨基脂肪酸甲酯组成的组的ω-羟基脂肪酸衍生物。在多个实施方案中,所述重组微生物可经过工程改造以进一步表达编码多肽的核酸序列,所述多肽包含EC 1.1.-.-的醇脱氢酶和1.2.99.的羧酸还原酶,其中所产生的ω-羟基脂肪酸衍生物为α,ω-二醇。另一方面,本公开涵盖一种重组微生物,其具有经过工程改造以表达编码多肽的至少两个核酸序列的路径,所述多肽包括EC 3.1.2.-或EC 3.1.1.5或3.1.2.14的硫酯酶;和本公开的CYP153A-还原酶杂合融合多肽变体。所述重组微生物可用于当在来自可再生原料的碳源存在下在发酵液中生长时体内产生ω-OH脂肪酸或ω-OH脂肪酸衍生物。在一个实施方案中,所述CYP153A-还原酶杂合融合多肽变体为自给自足的CYP153A-RedRhF杂合融合蛋白变体。
一方面,本公开提供一种产生ω-OH脂肪酸衍生物的方法,所述方法包括:(a)在包含含有碳源的可再生原料的培养基中培养本公开的重组微生物,和(b)从所述重组微生物或从所述培养基分离ω-OH脂肪酸衍生物。优选地,所述可再生原料是基于碳的,优选地其中所述基于碳的可再生原料是选自由玉米、甘蔗、高粱、甜菜、柳枝稷、青贮饲料、稻草、木材、纸浆、污水、垃圾、纤维素城市废物、烟道气、合成气、生物质水解液和二氧化碳组成的组。
本公开的另一方面提供一种细胞培养物,其包括本公开的重组宿主细胞。本公开的细胞培养物可产生ω-OH脂肪酸或其组合物。在一个实施方案中,所述细胞培养物产生ω-OH脂肪酸,包括C6、C7、C8、C9、C10、C11、C12、C13、C14、C15、C16、C17、C18、C19、C20、C8:1、C9:1、C10:1、C11:1、C12:1、C13:1、C14:1、C15:1、C16:1、C17:1、C18:1、C19:1和/或C20:1脂肪酸或脂肪酸衍生物或其组合物中的一者或多者。在一个实施方案中,所述细胞培养物产生不饱和ω-OH C16:1脂肪酸或其组合物。在另一实施方案中,所述细胞培养物产生饱和ω-OH C16脂肪酸或其组合物。在一个实施方案中,所述细胞培养物产生不饱和ω-OH C12:1脂肪酸或其组合物。在另一实施方案中,所述细胞培养物产生饱和ω-OH C12脂肪酸或其组合物。在一个实施方案中,所述细胞培养物产生不饱和ω-OH C14:1脂肪酸或其组合物。在另一实施方案中,所述细胞培养物产生饱和ω-OH C14脂肪酸或其组合物。在一个实施方案中,所述细胞培养物产生不饱和ω-OH C18:1脂肪酸或其组合物。在另一实施方案中,所述细胞培养物产生饱和ω-OH C18脂肪酸或其组合物。在一个实施方案中,所述细胞培养物产生不饱和ω-OH C10:1脂肪酸或其组合物。在另一实施方案中,所述细胞培养物产生饱和ω-OH C10脂肪酸或其组合物。在一个实施方案中,所述细胞培养物产生不饱和ω-OH C8:1脂肪酸或其组合物。在另一实施方案中,所述细胞培养物产生饱和ω-OH C8脂肪酸或其组合物。在一个实施方案中,所述细胞培养物产生不饱和ω-OH C20:1脂肪酸或其组合物。在另一实施方案中,所述细胞培养物产生饱和ω-OH C20脂肪酸或其组合物。在另一实施方案中,由所述重组宿主细胞产生另外的饱和或不饱和ω-OH脂肪酸或其组合物。
本公开的另一方面提供一种产生ω-OH脂肪酸的方法,所述方法包括用碳源培养本公开的宿主细胞;和收集ω-OH脂肪酸或其组合物。所述方法提供所产生的ω-OH脂肪酸的效价的增加/改进。所述方法涵盖收集ω-OH脂肪酸,所述脂肪酸为C6、C7、C8、C9、C10、C11、C12、C13、C14、C15、C16、C17、C18、C19、C20、C8:1、C9:1、C10:1、C11:1、C12:1、C13:1、C14:1、C15:1、C16:1、C17:1、C18:1、C19:1和/或C20:1脂肪酸或脂肪酸衍生物或其组合物。在一个实施方案中,所收集的ω-OH脂肪酸为不饱和ω-OH C16:1脂肪酸或其组合物。在另一实施方案中,所收集的ω-OH脂肪酸为饱和ω-OH C16脂肪酸或其组合物。在一个实施方案中,所收集的ω-OH脂肪酸为不饱和ω-OH C12:1脂肪酸或其组合物。在另一实施方案中,所收集的ω-OH脂肪酸为饱和ω-OH C12脂肪酸或其组合物。在一个实施方案中,所收集的ω-OH脂肪酸为不饱和ω-OH C14:1脂肪酸或其组合物。在另一实施方案中,所收集的ω-OH脂肪酸为饱和ω-OH C14脂肪酸或其组合物。在一个实施方案中,所收集的ω-OH脂肪酸为不饱和ω-OH C18:1脂肪酸或其组合物。在另一实施方案中,所收集的ω-OH脂肪酸为饱和ω-OH C18脂肪酸或其组合物。在一个实施方案中,所收集的ω-OH脂肪酸为不饱和ω-OH C10:1脂肪酸或其组合物。在另一实施方案中,所收集的ω-OH脂肪酸为饱和ω-OH C10脂肪酸或其组合物。在一个实施方案中,所收集的ω-OH脂肪酸为不饱和ω-OH C8:1脂肪酸或其组合物。在另一实施方案中,所收集的ω-OH脂肪酸为饱和ω-OH C8脂肪酸或其组合物。在一个实施方案中,所收集的ω-OH脂肪酸为不饱和ω-OH C20:1脂肪酸或其组合物。在另一实施方案中,所收集的ω-OH脂肪酸为饱和ω-OHC20脂肪酸或其组合物。在另一实施方案中,由本文所述的方法产生另外的饱和或不饱和ω-OH脂肪酸或其组合物。
本公开的另一方面提供一种CYP153A-还原酶杂合融合多肽变体,所述变体与SEQID NO:38具有至少约90%、91%、93%、94%、95%、96%、97%、98%或99%序列同一性并且在包括位置9、10、11、12、13、14、27、28、56、61、111、119、140、149、154、157、162、164、204、231、233、244、254、271、273、302、309、327、407、413、477、480、481、527、544、546、557、567、591、648、649、703、706、707、708、709、710、719、720、736、741、745、747、749、757、770、771、784的氨基酸位置处具有至少一个或多个突变,其中所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-OH脂肪酸或其组合物。所述CYP153A-还原酶杂合融合多肽变体在以下位置中的任一处或多处具有突变,包括位置D9N,其中天冬氨酸(D)被天冬酰胺(N)取代(即,置换);位置D9K,其中天冬氨酸(D)被赖氨酸(K)取代;位置D10Y,其中天冬氨酸(D)被酪氨酸(Y)取代;位置I11L,其中异亮氨酸(I)被亮氨酸(L)取代;位置Q12W,其中谷氨酰胺(Q)被色氨酸(W)取代;位置Q12R,其中谷氨酰胺(Q)被精氨酸(R)取代;位置Q12T,其中谷氨酰胺(Q)被苏氨酸(T)取代;位置S13K,其中丝氨酸(S)被赖氨酸(K)取代;位置R14F,其中精氨酸(R)被苯丙氨酸(F)取代;位置R27L,其中精氨酸(R)被亮氨酸(L)取代;位置Q28M,其中谷氨酰胺(Q)被甲硫氨酸(M)取代;位置Q28T,其中谷氨酰胺(Q)被苏氨酸(T)取代;位置P56Q,其中脯氨酸(P)被谷氨酰胺(Q)取代;位置N61L,其中天冬酰胺(N)被亮氨酸(L)取代;位置F111A,其中苯丙氨酸(F)被丙氨酸(A)取代;位置K119R,其中赖氨酸(K)被精氨酸(R)取代;位置S140N,其中丝氨酸(S)被天冬酰胺(N)取代;位置P149G,其中脯氨酸(P)被甘氨酸(G)取代;位置P149R,其中脯氨酸(P)被精氨酸(R)取代;位置V154G,其中缬氨酸(V)被甘氨酸(G)取代;位置S157R,其中丝氨酸(S)被精氨酸(R)取代;位置V162C,其中缬氨酸(V)被半胱氨酸(C)取代;位置A164N,其中丙氨酸(A)被天冬酰胺(N)取代;位置G204V,其中甘氨酸(G)被缬氨酸(V)取代;位置A231W,其中丙氨酸(A)被色氨酸(W)取代;位置A231Y,其中丙氨酸(A)被酪氨酸(Y)取代;位置A231V,其中丙氨酸(A)被缬氨酸(V)取代;位置S233L,其中丝氨酸(S)被亮氨酸(L)取代;位置S233V,其中丝氨酸(S)被缬氨酸(V)取代;位置A244R,其中丙氨酸(A)被精氨酸(R)取代;位置R254G,其中精氨酸(R)被甘氨酸(G)取代;位置E271D,其中谷氨酸(E)被天冬氨酸(D)取代;位置P273M,其中脯氨酸(P)被甲硫氨酸(M)取代;位置T302M,其中苏氨酸(T)被甲硫氨酸(M)取代;位置N309S,其中天冬酰胺(N)被丝氨酸(S)取代;位置P327D,其中脯氨酸(P)被天冬氨酸(D)取代;位置N407G,其中天冬酰胺(N)被甘氨酸(G)取代;位置Y413R,其中酪氨酸(Y)被精氨酸(R)取代;位置V451M,其中缬氨酸(V)被甲硫氨酸(M)取代;位置P477G,其中脯氨酸(P)被甘氨酸(G)取代;位置I480G,其中异亮氨酸(I)被甘氨酸(G)取代;位置G481I,其中甘氨酸(G)被异亮氨酸(I)取代;位置D527E,其中天冬氨酸(D)被谷氨酸(E)取代;位置D544N,其中天冬氨酸(D)被天冬酰胺(N)取代;位置P546G,其中脯氨酸(P)被甘氨酸(G)取代;位置E557R,其中谷氨酸(E)被精氨酸(R)取代;位置E557W,其中谷氨酸(E)被色氨酸(W)取代;位置E567S,其中谷氨酸(E)被丝氨酸(S)取代;位置E591Q,其中谷氨酸(E)被谷氨酰胺(Q)取代;位置V648L,其中缬氨酸(V)被亮氨酸(L)取代;位置S649I,其中丝氨酸(S)被异亮氨酸(I)取代;位置L703G,其中亮氨酸(L)被甘氨酸(G)取代;位置L706E,其中亮氨酸(L)被谷氨酸(E)取代;位置L706S,其中亮氨酸(L)被丝氨酸(S)取代;位置L706H,其中亮氨酸(L)被组氨酸(H)取代;位置D707E,其中天冬氨酸(D)被谷氨酸(E)取代;位置P708S,其中脯氨酸(P)被丝氨酸(S)取代;位置D709L,其中天冬氨酸(D)被亮氨酸(L)取代;位置V710C,其中缬氨酸(V)被半胱氨酸(C)取代;位置V710R,其中缬氨酸(V)被精氨酸(R)取代;位置V710Q,其中缬氨酸(V)被谷氨酰胺(Q)取代;位置R719W,其中精氨酸(R)被色氨酸(W)取代;位置D720V,其中天冬氨酸(D)被缬氨酸(V)取代;位置A736V,其中丙氨酸(A)被缬氨酸(V)取代;位置N741G,其中天冬酰胺(N)被甘氨酸(G)取代;位置P745K,其中脯氨酸(P)被赖氨酸(K)取代;位置P745R,其中脯氨酸(P)被精氨酸(R)取代;位置D747N,其中天冬氨酸(D)被天冬酰胺(N)取代;位置E749L,其中谷氨酸(E)被亮氨酸(L)取代;位置E749M,其中谷氨酸(E)被甲硫氨酸(M)取代;位置E757A,其中谷氨酸(E)被丙氨酸(A)取代;位置T770G,其中苏氨酸(T)被甘氨酸(G)取代;位置V771F,其中缬氨酸(V)被苯丙氨酸(F)取代;和位置M784I,其中甲硫氨酸(M)被异亮氨酸(I)取代。在一个实施方案中,所述CYP153A-还原酶杂合融合多肽变体为杂合cyp153A-RedRhF型融合蛋白变体。在另一实施方案中,如与由模板CYP153A-还原酶杂合融合多肽(例如,CYP153A-还原酶杂合融合多肽SEQ ID NO:6或SEQ ID NO:38)在相应宿主细胞中的表达产生的ω-OH脂肪酸的效价相比,在重组宿主细胞中的所述CYP153A-还原酶杂合融合多肽变体引起ω-OH脂肪酸的更高效价。在另一实施方案中,所述ω-OH脂肪酸为ω-OH脂肪酸组合物。
本公开的CYP153A-还原酶杂合融合多肽变体的实例为如序列表B和C所示的SEQID NO:47-164(下文段落[00147]和[00148])。
本公开的另一方面提供一种CYP153A-还原酶杂合融合多肽变体,其与SEQ ID NO:38具有至少约90%、91%、93%、94%、95%、96%、97%、98%或99%序列同一性并且在包括位置747、12、327、14、61、28、13、771、119、10、11、28、231、745、9、770、413、784、749、233、757和703的氨基酸位置处具有至少一个突变,其中所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-OH脂肪酸。所述CYP153A-还原酶杂合融合多肽变体在以下位置中的任一处或多处具有突变,包括位置D747N,其中天冬氨酸(D)被天冬酰胺(N)取代;位置Q12W,其中谷氨酰胺(Q)被色氨酸(W)取代;位置Q12R,其中谷氨酰胺(Q)被精氨酸(R)取代;位置Q12T,其中谷氨酰胺(Q)被苏氨酸(T)取代;位置P327D,其中脯氨酸(P)被天冬氨酸(D)取代;位置R14F,其中精氨酸(R)被苯丙氨酸(F)取代;位置N61L,其中天冬酰胺(N)被亮氨酸(L)取代;位置Q28M,其中谷氨酰胺(Q)被甲硫氨酸(M)取代;位置S13K,其中丝氨酸(S)被赖氨酸(K)取代;位置V771F,其中缬氨酸(V)被苯丙氨酸(F)取代;位置K119R,其中赖氨酸(K)被精氨酸(R)取代;位置D10Y,其中天冬氨酸(D)被酪氨酸(Y)取代;位置I11L,其中异亮氨酸(I)被亮氨酸(L)取代;位置Q28T,其中谷氨酰胺(Q)被苏氨酸(T)取代;位置P745R,其中脯氨酸(P)被精氨酸(R)取代;位置D9N,其中天冬氨酸(D)被天冬酰胺(N)取代;位置D9K,其中天冬氨酸(D)被赖氨酸(K)取代;位置T770G,其中苏氨酸(T)被甘氨酸(G)取代;位置Y413R,其中酪氨酸(Y)被精氨酸(R)取代;位置M784I,其中甲硫氨酸(M)被异亮氨酸(I)取代;位置E749L,其中谷氨酸(E)被亮氨酸(L)取代;位置S233L,其中丝氨酸(S)被亮氨酸(L)取代;位置E757A,其中谷氨酸(E)被丙氨酸(A)取代;位置L703G,其中亮氨酸(L)被甘氨酸(G)取代;和位置A231Y,其中丙氨酸(A)被酪氨酸(Y)取代。在一个实施方案中,所述CYP153A-还原酶杂合融合多肽变体为杂合CYP153A-RedRhF型融合蛋白变体。在另一实施方案中,如与由模板CYP153A-还原酶杂合融合多肽(例如,CYP153A-还原酶杂合融合多肽SEQ ID NO:6或SEQID NO:38)在相应宿主细胞中的表达产生的ω-OH脂肪酸的效价相比,在重组宿主细胞中的所述CYP153A-还原酶杂合融合多肽变体引起ω-OH脂肪酸的更高效价。在另一实施方案中,所述CYP153A-还原酶杂合融合多肽变体(和相应多核苷酸序列)包括如序列表B和C所示的SEQ ID NO:47-164。在另一实施方案中,所述ω-OH脂肪酸为ω-OH脂肪酸组合物。
本公开的另一方面提供一种CYP153A-还原酶杂合融合多肽变体,其与SEQ ID NO:98具有至少约90%、91%、93%、94%、95%、96%、97%、98%或99%序列同一性并且在包括位置12、27、119、140、157、159、233和244的氨基酸位置处具有至少一个突变,其中所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-OH脂肪酸。在一个实施方案中,所述CYP153A-还原酶杂合融合多肽变体在以下位置中的任一处或多处具有突变,包括位置Q12W,其中谷氨酰胺(Q)被色氨酸(W)取代;位置R27L,其中精氨酸(R)被亮氨酸(L)取代;位置K119R,其中赖氨酸(K)被精氨酸(R)取代;位置S140N,其中丝氨酸(S)被天冬酰胺(N)取代;位置S157R,其中丝氨酸(S)精氨酸(R)取代;位置V159M,其中缬氨酸(V)被甲硫氨酸(M)取代;位置S233L,其丝氨酸(S)被亮氨酸(L)取代;和位置A244R,其中丙氨酸(A)被精氨酸(R)取代。
本公开的另一方面提供一种CYP153A-还原酶杂合融合多肽变体,其与SEQ ID NO:100具有至少约90%、91%、93%、94%、95%、96%、97%、98%或99%序列同一性并且在包括位置12、28、61、119、231、309、413和480的氨基酸位置处具有至少一个突变,其中所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-OH脂肪酸。所述CYP153A-还原酶杂合融合多肽变体在以下位置中的任一处或多处具有突变,包括位置Q12R,其中谷氨酰胺(Q)被精氨酸(R)取代;位置Q28M,其中谷氨酰胺(Q)被甲硫氨酸(M)取代;位置N61L,其中天冬酰胺(N)被亮氨酸(L)取代;位置K119R,其中赖氨酸(K)被精氨酸(R)取代;位置A231V,其中丙氨酸(A)被缬氨酸(V)取代;位置N309S,其中天冬酰胺(N)被丝氨酸(S)取代;位置Y413R,其中酪氨酸(Y)被精氨酸(R)取代;和位置I480G,其中异亮氨酸(I)被甘氨酸(G)取代。
本公开的另一方面提供一种CYP153A-还原酶杂合融合多肽变体,其与氨基酸序列SEQ ID NO:38具有至少约80%、81%、82%、83%、84%、85%、86%、87%、88%或89%序列同一性,其中所述CYP153A-还原酶杂合融合多肽变体包含在氨基酸位置12处的突变和在以下氨基酸位置中的每一者处的突变:(a)SEQ ID NO:38的27、119、140、157、159、233和244;(b)SEQ ID NO:38的28、61、119、231、309、413和480;(c)SEQ ID NO:38的119、231和480;(d)SEQ ID NO:38的28、77、119;141、231和407;(e)SEQ ID NO:38的28、61、141、231和407;(f)SEQ ID NO:38的28、119、231和244;(g)SEQ ID NO:38的28、407和480;(h)SEQ ID NO:38的141、231、413和481;(i)SEQ ID NO:38的28、111、231和407;(j)SEQ ID NO:38的28、61、140和149;(k)SEQ ID NO:38的28、77、119、159、231、254、407和480;(l)SEQ ID NO:38的28、254、309、407和451;(m)SEQ ID NO:38的28、254、309、407和480;或(n)SEQ ID NO:38的28、309、407、451和480;其中所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-羟基化脂肪酸。本公开的另一方面提供一种CYP153A-还原酶杂合融合多肽变体,其与氨基酸序列SEQ ID NO:38具有至少约90%、91%、92%、93%、94%、95%、96%、97%、98%或99%序列同一性,其中所述CYP153A-还原酶杂合融合多肽变体包含在氨基酸位置12处的突变和在以下氨基酸位置中的每一者处的突变:(a)SEQ ID NO:38的27、119、140、157、159、233和244;(b)SEQ ID NO:38的28、61、119、231、309、413和480;(c)SEQ ID NO:38的119、231和480;(d)SEQ ID NO:38的28、77、119;141、231和407;(e)SEQ ID NO:38的28、61、141、231和407;(f)SEQ ID NO:38的28、119、231和244;(g)SEQ ID NO:38的28、407和480;(h)SEQ IDNO:38的141、231、413和481;(i)SEQ ID NO:38的28、111、231和407;(j)SEQ ID NO:38的28、61、140和149;(k)SEQ ID NO:38的28、77、119、159、231、254、407和480;(l)SEQ ID NO:38的28、254、309、407和451;(m)SEQ ID NO:38的28、254、309、407和480;或(n)SEQ ID NO:38的28、309、407、451和480;其中所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-羟基化脂肪酸。在多个实施方案中,在(a)氨基酸位置SEQ ID NO:38的12、27、119、140、157、159、233和244处的所述突变为氨基酸取代。在多个实施方案中,在(b)氨基酸位置SEQ IDNO:38的12、28、61、119、231、309、413和480处的所述突变为氨基酸取代。在多个实施方案中,在(c)氨基酸位置SEQ ID NO:38的12、119、231和480处的所述突变为氨基酸取代。在多个实施方案中,在(d)氨基酸位置SEQ ID NO:38的12、28、77、119;141、231和407处的所述突变为氨基酸取代。在多个实施方案中,在(e)氨基酸位置SEQ ID NO:38的12、28、61、141、231和407处的所述突变为氨基酸取代。在多个实施方案中,在(f)氨基酸位置SEQ ID NO:38的12、28、119、231和244处的所述突变为氨基酸取代。在多个实施方案中,在(g)氨基酸位置SEQ ID NO:38的12、28、407和480处的所述突变为氨基酸取代。在多个实施方案中,在(h)氨基酸位置SEQ ID NO:38的12、141、231、413和481处的所述突变为氨基酸取代。在多个实施方案中,在(i)氨基酸位置SEQ ID NO:38的12、28、111、231和407处的所述突变为氨基酸取代。在多个实施方案中,在(j)氨基酸位置SEQ ID NO:38的12、28、61、140和149处的所述突变为氨基酸取代。在多个实施方案中,在(k)氨基酸位置12、28、77、119、159、231、254、407和480处的所述突变为氨基酸取代。在多个实施方案中,在(l)氨基酸位置SEQ ID NO:38的12、28、254、309、407和451处的所述突变为氨基酸取代。在多个实施方案中,在(m)氨基酸位置SEQ ID NO:38的12、28、254、309、407和480处的所述突变为氨基酸取代。在多个实施方案中,在(n)氨基酸位置SEQ ID NO:38的12、28、309、407、451和480处的所述突变为氨基酸取代。在一个实施方案中,在(a)氨基酸位置SEQ ID NO:38的12、27、119、140、157、159、233和244处的所述突变分别为Q12W、R27L、K119R、S140N、S157R、V159M、S233L和A244R。在一个实施方案中,在(b)氨基酸位置SEQ ID NO:38的12、28、61、119、231、309、413和480处的所述突变分别为Q12R、Q28M、N61L、K119R、A231V、N309S、Y413R和I480G。在一个实施方案中,在(c)氨基酸位置SEQ ID NO:38的12、119、231和480处的所述突变分别为Q12R、K119R、A231V和I480G。在一个实施方案中,在(d)氨基酸位置SEQ ID NO:38的12、28、77、119;141、231和407处的所述突变分别为Q12T、Q28M、R77Q、K119R、V141T、A231W和N407G。在一个实施方案中,在(e)氨基酸位置SEQ ID NO:38的12、28、61、141、231和407处的所述突变分别为Q12R、Q28M、N61L、V141T、A231Y和N407G。在一个实施方案中,在(f)氨基酸位置SEQ ID NO:38的12、28、119、231和244处的所述突变分别为Q12W、Q28M、K119R、A231Y和A244R。在一个实施方案中,在(g)氨基酸位置SEQ ID NO:38的12、28、407和480处的所述突变分别为Q12W、Q28T、N407G和I480G。在一个实施方案中,在(h)氨基酸位置SEQ ID NO:38的12、141、231、413和481处的所述突变分别为Q12R、V141T、A231Y、Y413R和G481I。在一个实施方案中,在(i)氨基酸位置SEQ ID NO:38的12、28、111、231和407处的所述突变分别为Q12T、Q28M、F111A、A231V和N407G。在一个实施方案中,在(j)氨基酸位置SEQ ID NO:38的12、28、61、140和149处的所述突变分别为Q12T、Q28M、N61L、S140N和P149R。在一个实施方案中,在(k)氨基酸位置12、28、77、119、159、231、254、407和480处的所述突变分别为Q12W、Q28T、R77Q、K119R、V159M、A231Y、R254G、N407G和I480G。在一个实施方案中,在(l)氨基酸位置SEQ ID NO:38的12、28、254、309、407和451处的所述突变分别为Q12W、Q28T、R254G、N309S、N407G和V451M。在一个实施方案中,在(m)氨基酸位置SEQ ID NO:38的12、28、254、309、407和480处的所述突变分别为Q12W、Q28T、R254G、N309S、N407G和I480G。在一个实施方案中,在(n)氨基酸位置SEQ IDNO:38的12、28、309、407、451和480处的所述突变分别为Q12W、Q28T、N309S、N407G、V451M和I480G。在一个优选实施方案中,以上(a)的CYP153A-还原酶杂合融合多肽变体进一步包含在氨基酸位置SEQ ID NO:38的141、231和407中的每一者处,或在氨基酸位置SEQ ID NO:38的231、407、451、757、770和784中的每一者处,或在氨基酸位置SEQ ID NO:38的231、407、591、643、757和784中的每一者处的突变。在多个实施方案中,在氨基酸位置SEQ ID NO:38的141、231和407中的每一者处的所述进一步突变为氨基酸取代。另外,在多个实施方案中,在氨基酸位置SEQ ID NO:38的231、407、451、757、770和784中的每一者处的所述进一步突变为氨基酸取代。另外,在多个实施方案中,在氨基酸位置SEQ ID NO:38的231、407、591、643、757和784中的每一者处的所述进一步突变为氨基酸取代。优选地,在氨基酸位置SEQID NO:38的141、231和407中的每一者处的所述进一步突变分别为V141T、A231Y和N407G。另外,优选地,在氨基酸位置SEQ ID NO:38的231、407、451、757、770和784中的每一者处的所述突变分别为A231Y、N407G、V451M、E757A、T770G和M784I。另外,优选地,在氨基酸位置SEQID NO:38的231、407、591、643、757和784中的每一者处的所述突变分别为A231Y、N407G、E591Q、R643H、E757A和M784I。更优选地,本公开的CYP153A-还原酶杂合融合多肽变体包含氨基酸序列SEQ ID NO:146、SEQ ID NO:150或SEQ ID NO:160。在本公开的其它实施方案中,所述CYP153A-还原酶杂合融合多肽变体包含氨基酸序列SEQ ID NO:98、SEQ ID NO:100、SEQ ID NO:102、SEQ ID NO:104、SEQ ID NO:106、SEQ ID NO:108、SEQ ID NO:110、SEQID NO:112、SEQ ID NO:114、SEQ ID NO:116、SEQ ID NO:118、SEQ ID NO:120、SEQ ID NO:122和SEQ ID NO:124中的任一者。
另一方面,本公开提供一种CYP153A-还原酶杂合融合多肽变体,其包含与氨基酸序列SEQ ID NO:38的至少约80%、81%、82%、83%、84%、85%、86%、87%、88%或89%序列同一性,其中所述CYP153A-还原酶杂合融合多肽变体包含在RhF结构域(或RhF还原酶结构域,或Red450RhF结构域,或Red450RhF还原酶结构域,或P450RhF结构域,或P450RhF还原酶结构域)中在以下氨基酸位置中的每一者处的突变:(a)SEQ ID NO:38的527、544、719、757、771和784;(b)SEQ ID NO:38的527、544和557;(c)SEQ ID NO:38的770和784;(d)SEQID NO:38的527、591、648、719、757、771和784;(e)SEQ ID NO:38的527、591、648、757和771;(f)SEQ ID NO:38的527、544、770和784;(g)SEQ ID NO:38的527、557、770和784;(h)SEQ IDNO:38的557、757和770;(i)SEQ ID NO:38的557、757和771;或(j)SEQ ID NO:38的757和770;其中所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-羟基化脂肪酸。另一方面,本公开提供一种CYP153A-还原酶杂合融合多肽变体,其包含与氨基酸序列SEQ IDNO:38的至少约90%、91%、92%、93%、94%、95%、96%、97%、98%或99%序列同一性,其中所述CYP153A-还原酶杂合融合多肽变体包含在RhF结构域(或RhF还原酶结构域,或Red450RhF结构域,或Red450RhF还原酶结构域,或P450RhF结构域,或P450RhF还原酶结构域)中在以下氨基酸位置中的每一者处的突变:(a)SEQ ID NO:38的527、544、719、757、771和784;(b)SEQ ID NO:38的527、544和557;(c)SEQ ID NO:38的770和784;(d)SEQ ID NO:38的527、591、648、719、757、771和784;(e)SEQ ID NO:38的527、591、648、757和771;(f)SEQID NO:38的527、544、770和784;(g)SEQ ID NO:38的527、557、770和784;(h)SEQ ID NO:38的557、757和770;(i)SEQ ID NO:38的557、757和771;或(j)SEQ ID NO:38的757和770;其中所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-羟基化脂肪酸。在多个实施方案中,在(a)氨基酸位置SEQ ID NO:38的527、544、719、757、771和784处的所述突变为氨基酸取代。在多个实施方案中,在(b)氨基酸位置SEQ ID NO:38的527、544和557处的所述突变为氨基酸取代。在多个实施方案中,在(c)氨基酸位置SEQ ID NO:38的770和784处的所述突变为氨基酸取代。在多个实施方案中,在(d)氨基酸位置SEQ ID NO:38的527、591、648、719、757、771和784处的所述突变为氨基酸取代。在多个实施方案中,在(e)氨基酸位置SEQID NO:38的527、591、648、757和771处的所述突变为氨基酸取代。在多个实施方案中,在(f)氨基酸位置SEQ ID NO:38的527、544、770和784处的所述突变为氨基酸取代。在多个实施方案中,在(g)氨基酸位置SEQ ID NO:38的527、557、770和784处的所述突变为氨基酸取代。在多个实施方案中,在(h)氨基酸位置SEQ ID NO:38的557、757和770处的所述突变为氨基酸取代。在多个实施方案中,在(i)氨基酸位置SEQ ID NO:38的557、757和771处的所述突变为氨基酸取代。在多个实施方案中,在(j)氨基酸位置SEQ ID NO:38的757和770处的所述突变为氨基酸取代。在一个实施方案中,在(a)氨基酸位置SEQ ID NO:38的527、544、719、757、771和784处的所述突变分别为D527E、D544N、R719W、E757A、V771F和M784I。在一个实施方案中,在(b)氨基酸位置SEQ ID NO:38的527、544和557处的所述突变分别为D527E、D544N和E557R。在一个实施方案中,在(c)氨基酸位置SEQ ID NO:38的770和784处的所述突变分别为T770G和M784I。在一个实施方案中,在(d)氨基酸位置SEQ ID NO:38的527、591、648、719、757、771和784处的所述突变分别为D527E、E591Q、V648L、R719W、E757A、V771F和M784I。在一个实施方案中,在(e)氨基酸位置SEQ ID NO:38的527、591、648、757和771处的所述突变分别为D527E、E591Q、V648L、E757A和V771F。在一个实施方案中,在(f)氨基酸位置SEQ ID NO:38的527、544、770和784处的所述突变分别为D527E、D544N、T770G和M784I。在一个实施方案中,在(g)氨基酸位置SEQ ID NO:38的527、557、770和784处的所述突变分别为D527E、E557R、T770G和M784I。在一个实施方案中,在(h)氨基酸位置SEQ ID NO:38的557、757和770处的所述突变分别为E557W、E757A和T770G。在一个实施方案中,在(i)氨基酸位置SEQ IDNO:38的557、757和771处的所述突变分别为E557R、E757A和V771F。在一个实施方案中,在(j)氨基酸位置SEQ ID NO:38的757和770处的所述突变分别为E757A和T770G。在本公开的一些优选实施方案中,所述CYP153A-还原酶杂合融合多肽变体包含氨基酸序列SEQ ID NO:126、SEQ ID NO:128、SEQ ID NO:130、SEQ ID NO:132、SEQ ID NO:134、SEQ ID NO:136、SEQID NO:138、SEQ ID NO:140、SEQ ID NO:142和SEQ ID NO:144中的任一者。
另一方面,本公开提供一种CYP153A-还原酶杂合融合多肽变体,其包含与氨基酸序列SEQ ID NO:38的至少约90%、91%、92%、93%、94%、95%、96%、97%、98%或99%序列同一性,其中所述CYP153A-还原酶杂合融合多肽变体包含在以下位置中的每一者处的突变:(a)SEQ ID NO:38的141、231、233和254;(b)SEQ ID NO:38的141、231、233和244;(c)SEQID NO:38的141、231、244、451、557、749和770;(d)SEQ ID NO:38的27、28、61、141、149和231;(e)SEQ ID NO:38的141、157、231、233、244、757和784;(f)SEQ ID NO:38的28、61、140、141、231、233和271;或(g)SEQ ID NO:38的231、233、254和557;其中所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-羟基化脂肪酸。另一方面,本公开提供一种CYP153A-还原酶杂合融合多肽变体,其包含与氨基酸序列SEQ ID NO:38的至少约80%、81%、82%、83%、84%、85%、86%、87%、88%或89%序列同一性,其中所述CYP153A-还原酶杂合融合多肽变体包含在以下位置中的每一者处的突变:(a)SEQ ID NO:38的141、231、233和254;(b)SEQ ID NO:38的141、231、233和244;(c)SEQ ID NO:38的141、231、244、451、557、749和770;(d)SEQ ID NO:38的27、28、61、141、149和231;(e)SEQ ID NO:38的141、157、231、233、244、757和784;(f)SEQ ID NO:38的28、61、140、141、231、233和271;或(g)SEQ ID NO:38的231、233、254和557;其中所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-羟基化脂肪酸。在多个实施方案中,在(a)氨基酸位置SEQ ID NO:38的141、231、233和254处的所述突变为氨基酸取代。在多个实施方案中,在(b)氨基酸位置SEQ ID NO:38的141、231、233和244处的所述突变为氨基酸取代。在多个实施方案中,在(c)氨基酸位置SEQ ID NO:38的141、231、244、451、557、749和770处的所述突变为氨基酸取代。在多个实施方案中,在(d)氨基酸位置SEQ ID NO:38的27、28、61、141、149和231处的所述突变为氨基酸取代。在多个实施方案中,在(e)氨基酸位置SEQ ID NO:38的141、157、231、233、244、757和784处的所述突变为氨基酸取代。在多个实施方案中,在(f)氨基酸位置SEQ ID NO:38的28、61、140、141、231、233和271处的所述突变为氨基酸取代。在多个实施方案中,在(g)氨基酸位置SEQ IDNO:38的231、233、254和557处的所述突变为氨基酸取代。在一个实施方案中,在(a)氨基酸位置SEQ ID NO:38的141、231、233和254处的所述突变分别为V141T、A231Y、L233S和R254G。在一个实施方案中,在(b)氨基酸位置SEQ ID NO:38的141、231、233和244处的所述突变分别为V141T、A231Y、L233S和R244A。在一个实施方案中,在(c)氨基酸位置SEQ ID NO:38的141、231、244、451、557、749和770处的所述突变分别为V141T、A231Y、R244A、V451M、E557W、E749L和T770G。在一个实施方案中,在(d)氨基酸位置SEQ ID NO:38的27、28、61、141、149和231处的所述突变分别为L27R、Q28M、N61L、V141T、P149G和A231Y。在一个实施方案中,在(e)氨基酸位置SEQ ID NO:38的141、157、231、233、244、757和784处的所述突变分别为V141T、R157S、A231Y、L233S、R244A、E757A和M784I。在一个实施方案中,在(f)氨基酸位置SEQ IDNO:38的28、61、140、141、231、233和271处的所述突变分别为Q28M、N61L、N140S、V141T、A231Y、L233S和E271D。在一个实施方案中,在(g)氨基酸位置SEQ ID NO:38的231、233、254和557处的所述突变分别为A231Y、L233S、R254G和E557W。在本公开的一些优选实施方案中,本公开的CYP153A-还原酶杂合融合多肽变体包含氨基酸序列SEQ ID NO:148、SEQ ID NO:152、SEQ ID NO:154、SEQ ID NO:156、SEQ ID NO:158、SEQ ID NO:162和SEQ ID NO:164中的任一者。
另一方面,本公开提供一种CYP153A-还原酶杂合融合多肽变体,其包含与氨基酸序列SEQ ID NO:98的至少约80%、81%、82%、83%、84%、85%、86%、87%、88%或89%序列同一性,其中所述CYP153A-还原酶杂合融合多肽变体包含在以下氨基酸位置中的每一者处的突变:(a)SEQ ID NO:98的141、231和407;(b)SEQ ID NO:98的141、231、233和254;(c)SEQ ID NO:98的231、407、451、757、770和784;(d)SEQ ID NO:98的141、231、233和244;(e)SEQ ID NO:98的141、231、244、451、557、749和770;(f)SEQ ID NO:98的27、28、61、141、149和231;(g)SEQ ID NO:98的27、119、140、141、159、231、757和784;(h)SEQ ID NO:98的231、407、591、643、757和784;(i)SEQ ID NO:98的28、61、140、141、231、233和271;或(j)SEQ IDNO:98的231、233和254;其中所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-羟基化脂肪酸。另一方面,本公开提供一种CYP153A-还原酶杂合融合多肽变体,其包含与氨基酸序列SEQ ID NO:98的至少约90%、91%、92%、93%、94%、95%、96%、97%、98%或99%序列同一性,其中所述CYP153A-还原酶杂合融合多肽变体包含在以下氨基酸位置中的每一者处的突变:(a)SEQ ID NO:98的141、231和407;(b)SEQ ID NO:98的141、231、233和254;(c)SEQ ID NO:98的231、407、451、757、770和784;(d)SEQ ID NO:98的141、231、233和244;(e)SEQ ID NO:98的141、231、244、451、557、749和770;(f)SEQ ID NO:98的27、28、61、141、149和231;(g)SEQ ID NO:98的27、119、140、141、159、231、757和784;(h)SEQ ID NO:98的231、407、591、643、757和784;(i)SEQ ID NO:98的28、61、140、141、231、233和271;或(j)SEQ ID NO:98的231、233和254;其中所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-羟基化脂肪酸。在多个实施方案中,在(a)氨基酸位置SEQ ID NO:98的141、231和407处的所述突变为氨基酸取代。在多个实施方案中,在(b)氨基酸位置SEQ ID NO:98的141、231、233和254处的所述突变为氨基酸取代。在多个实施方案中,在(c)氨基酸位置SEQID NO:98的231、407、451、757、770和784处的所述突变为氨基酸取代。在多个实施方案中,在(d)氨基酸位置SEQ ID NO:98的141、231、233和244处的所述突变为氨基酸取代。在多个实施方案中,在(e)氨基酸位置SEQ ID NO:98的141、231、244、451、557、749和770处的所述突变为氨基酸取代。在多个实施方案中,在(f)氨基酸位置SEQ ID NO:98的27、28、61、141、149和231处的所述突变为氨基酸取代。在多个实施方案中,在(g)氨基酸位置SEQ ID NO:98的27、119、140、141、159、231、757和784处的所述突变为氨基酸取代。在多个实施方案中,在(h)氨基酸位置SEQ ID NO:98的231、407、591、643、757和784处的所述突变为氨基酸取代。在多个实施方案中,在(i)氨基酸位置SEQ ID NO:98的28、61、140、141、231、233和271处的所述突变为氨基酸取代。在多个实施方案中,在(j)氨基酸位置SEQ ID NO:38的231、233和254处的所述突变为氨基酸取代。在一个实施方案中,在(a)氨基酸位置SEQ ID NO:98的141、231和407处的所述突变分别为V141T、A231Y和N407G。在一个实施方案中,在(b)氨基酸位置SEQ ID NO:98的141、231、233和254处的所述突变分别为V141T、A231Y、L233S和R254G。在一个实施方案中,在(c)氨基酸位置SEQ ID NO:98的231、407、451、757、770和784处的所述突变分别为A231Y、N407G、V451M、E757A、T770G和M784I。在一个实施方案中,在(d)氨基酸位置SEQ ID NO:98的141、231、233和244处的所述突变分别为V141T、A231Y、L233S和R244A。在一个实施方案中,在(e)氨基酸位置SEQ ID NO:98的141、231、244、451、557、749和770处的所述突变分别为V141T、A231Y、R244A、V451M、E557W、E749L和T770G。在一个实施方案中,在(f)氨基酸位置SEQ ID NO:98的27、28、61、141、149和231处的所述突变分别为L27R、Q28M、N61L、V141T、P149G和A231Y。在一个实施方案中,在(g)氨基酸位置SEQ ID NO:98的141、157、231、233、244、757和784处的所述突变分别为V141T、R157S、A231Y、L233S、R244A、E757A和M784I。在一个实施方案中,在(h)氨基酸位置SEQ ID NO:98的231、407、591、643、757和784处的所述突变分别为A231Y、N407G、E591Q、R643H、E757A和M784I。在一个实施方案中,在(i)氨基酸位置SEQ ID NO:98的28、61、140、141、231、233和271处的所述突变分别为Q28M、N61L、N140S、V141T、A231Y、L233S和E271D。在一个实施方案中,在(j)氨基酸位置SEQID NO:98的231、233、254和557处的所述突变分别为A231Y、L233S、R254G和E557W。在本公开的一些优选实施方案中,本公开的CYP153A-还原酶杂合融合多肽变体包含氨基酸序列SEQID NO:146、SEQ ID NO:148、SEQ ID NO:150、SEQ ID NO:152、SEQ ID NO:154、SEQ ID NO:156、SEQ ID NO:158、SEQ ID NO:160;SEQ ID NO:162和SEQ ID NO:164中的任一者。
另一方面,本公开提供一种CYP153A-还原酶杂合融合多肽变体,其包含与氨基酸序列SEQ ID NO:38或SEQ ID NO:98的至少约90%、91%、92%、93%、94%、95%、96%、97%、98%或99%序列同一性,其中所述CYP153A-还原酶杂合融合多肽变体包含在位置10、11、12、27、28、111、119、140、141、149、157、159、197、231、233、244、254、407和477处的一种或多种突变。所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-羟基化脂肪酸。另一方面,本公开提供一种CYP153A-还原酶杂合融合多肽变体,其包含与氨基酸序列SEQID NO:38或SEQ ID NO:98的至少约80%、81%、82%、83%、84%、85%、86%、87%、88%或89%序列同一性,其中所述CYP153A-还原酶杂合融合多肽变体包含一种或多种突变,其包括(a)Q12W、R27L、Q28M、K119R、V141T、S157R、V159M、A231Y、S233L、A244R(SEQ ID NO:166);(b)Q12W、Q28M、K119R、S140N、S157R、V159M、S233L、A244R、R254G、N407G(SEQ ID NO:168);(c)Q12W、R27L、F111A、K119R、V141T、S157R、V159M、A231Y、S233L、A244R、R254G(SEQ ID NO:170);(d)Q12W、Q28M、K119R、S140N、P149G、S157R、V159M、A231Y、S233L、N407G(SEQ ID NO:172);(e)Q12W、R27L、Q28M、K119R、S140N、S157R、V159M、S233L、A244R、N407G(SEQ ID NO:174);(f)D10Y、I11L、Q12W、Q28M、K119R、V141T、V159M、A231Y、S233L、A244R、N407G(SEQ IDNO:176);(g)I11L、Q12W、R27L、Q28M、K119R、V141T、S157R、V159M、A197T、A231Y、S233L、A244R、N407G、P477G(SEQ ID NO:178);(h)I11L、Q12W、Q28M、K119R、V141T、S157R、V159M、A197T、A231Y、S233L、A244R、N407G(SEQ ID NO:180);和(i)I11L、Q12W、R27L、Q28M、K119R、V141T、P149G、S157R、V159M、A231Y、S233L、N407G(SEQ ID NO:182)。在多个实施方案中,在(a)-(i)下的所述突变为氨基酸取代。在本公开的一些优选实施方案中,本公开的CYP153A-还原酶杂合融合多肽变体包含氨基酸序列SEQ ID NO:166、SEQ ID NO:168、SEQ ID NO:170、SEQ ID NO:172、SEQ ID NO:174、SEQ ID NO:176、SEQ ID NO:178、SEQ ID NO:180和SEQ ID NO:182中的任一者。
本公开预期一种CYP153A-还原酶杂合融合多肽变体,其与氨基酸序列SEQ ID NO:38具有至少90%序列同一性,其中所述CYP153A-还原酶杂合融合多肽变体具有在氨基酸位置12处的突变和在以下氨基酸位置中的每一者处的突变:(a)SEQ ID NO:38的12、27、28、119、141、157、159、231、233和244;(b)SEQ ID NO:38的12、28、119、140、157、159、233、244、254和407;(c)SEQ ID NO:38的12、27、111、119、141、157、159、231、233、244和254;(d)SEQID NO:38的12、28、119、140、149、157、159、231、233和407;(e)SEQ ID NO:38的12、27、28、119、140、157、159、233、244和407;(f)SEQ ID NO:38的10、11、12、28、119、141、159、231、233、244和407;(g)SEQ ID NO:38的11、12、27、28、119、141、157、159、197、231、233、244、407和477;(h)SEQ ID NO:38的11、12、28、119、141、157、159、197、231、233、244和407;或(i)SEQID NO:38的11、12、27、28、119、141、149、157、159、231、233和407;其中所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-羟基化脂肪酸。
在一个特定方面,本公开提供如技术方案1的CYP153A-还原酶杂合融合多肽变体,其中:(a)在氨基酸位置SEQ ID NO:38的12、27、28、119、141、157、159、231、233和244处的所述突变分别为Q12W、R27L、Q28M、K119R、V141T、S157R、V159M、A231Y、S233L和A244R;(b)在氨基酸位置SEQ ID NO:38的12、28、119、140、157、159、233、244、254和407处的所述突变分别为Q12W、Q28M、K119R、S140N、S157R、V159M、S233L、A244R、R254G和N407G;(c)在氨基酸位置SEQ ID NO:38的12、27、111、119、141、157、159、231、233、244和254处的所述突变分别为Q12W、R27L、F111A、K119R、V141T、S157R、V159M、A231Y、S233L、A244R和R254G;(d)在氨基酸位置SEQ ID NO:38的12、28、119、140、149、157、159、231、233和407处的所述突变分别为Q12W、Q28M、K119R、S140N、P149G、S157R、V159M、A231Y、S233L和N407G;(e)在氨基酸位置SEQID NO:38的12、27、28、119、140、157、159、233、244和407处的所述突变分别为Q12W、R27L、Q28M、K119R、S140N、S157R、V159M、S233L、A244R和N407G;(f)在氨基酸位置SEQ ID NO:38的10、11、12、28、119、141、159、231、233、244和407处的所述突变分别为D10Y、I11L、Q12W、Q28M、K119R、V141T、V159M、A231Y、S233L、A244R和N407G;(g)在氨基酸位置SEQ ID NO:38的11、12、27、28、119、141、157、159、197、231、233、244、407和477处的所述突变分别为I11L、Q12W、R27L、Q28M、K119R、V141T、S157R、V159M、A197T、A231Y、S233L、A244R、N407G和P477G;(h)在氨基酸位置SEQ ID NO:38的11、12、28、119、141、157、159、197、231、233、244和407处的所述突变分别为I11L、Q12W、Q28M、K119R、V141T、S157R、V159M、A197T、A231Y、S233L、A244R和N407G;和(i)在氨基酸位置SEQ ID NO:38的11、12、27、28、119、141、149、157、159、231、233和407处的所述突变分别为I11L、Q12W、R27L、Q28M、K119R、V141T、P149G、S157R、V159M、A231Y、S233L和N407G。
另一方面,本公开提供如技术方案2的CYP153A-还原酶杂合融合多肽变体,其中:(a)(a)的所述CYP153A-还原酶杂合融合多肽变体具有氨基酸序列SEQ ID NO:166;(b)(b)的所述CYP153A-还原酶杂合融合多肽变体具有氨基酸序列SEQ ID NO:168;(c)(c)的所述CYP153A-还原酶杂合融合多肽变体具有氨基酸序列SEQ ID NO:170;(d)(d)的所述CYP153A-还原酶杂合融合多肽变体具有氨基酸序列SEQ ID NO:172;(e)(e)的所述CYP153A-还原酶杂合融合多肽变体具有氨基酸序列SEQ ID NO:174;(f)(f)的所述CYP153A-还原酶杂合融合多肽变体具有氨基酸序列SEQ ID NO:176;(g)(g)的所述CYP153A-还原酶杂合融合多肽变体具有氨基酸序列SEQ ID NO:178;(h)(h)的所述CYP153A-还原酶杂合融合多肽变体具有氨基酸序列SEQ ID NO:180;和(i)(i)的所述CYP153A-还原酶杂合融合多肽变体具有氨基酸序列SEQ ID NO:182。
在一个实施方案中,所述CYP153A-还原酶杂合融合多肽变体包括但不限于SEQ IDNO:166、SEQ ID NO:168、SEQ ID NO:170、SEQ ID NO:172、SEQ ID NO:174、SEQ ID NO:176、SEQ ID NO:178、SEQ ID NO:180和SEQ ID NO:182。在另一实施方案中,如与通过CYP153A-还原酶杂合融合多肽SEQ ID NO:6或SEQ ID NO:38在相应宿主细胞中的表达产生的ω-羟基化脂肪酸的效价相比,所述CYP153A-还原酶杂合融合多肽变体在重组宿主细胞中的表达引起ω-羟基化脂肪酸的较高效价。在另一实施方案中,所述CYP153A-还原酶杂合融合多肽变体为杂合CYP153A-RedRhF融合蛋白变体。在另一实施方案中,重组宿主细胞表达本公开的CYP153A-还原酶杂合融合多肽变体。在另一实施方案中,所述重组宿主细胞进一步表达EC 3.1.2.-、EC 3.1.1.5或EC 3.1.2.14的硫酯酶多肽。在另一实施方案中,当在含有碳源的培养基中培养时,所述重组宿主细胞产生ω-羟基化脂肪酸组合物,其具有比由表达具有SEQ ID NO:38或SEQ ID NO:6的相应CYP153A-还原酶杂合融合多肽的宿主细胞产生的ω-羟基化脂肪酸组合物的效价大至少10%、大至少15%、大至少20%、大至少25%或大至少30%的效价。在另一实施方案中,本公开提供一种细胞培养物,其包括如上文所预期的重组宿主细胞。
另一方面,本公开提供一种产生ω-羟基化脂肪酸的方法,步骤包括:(i)在碳源存在下培养重组宿主细胞或所述细胞培养物;和(ii)收集ω-羟基化脂肪酸。
本公开进一步预期一种重组微生物,其包含经过工程改造以表达编码多肽的至少两个核酸序列的路径,所述多肽包括:(i)EC 3.1.2.-、EC 3.1.1.5或EC 3.1.2.14的硫酯酶;和(ii)CYP153A-还原酶杂合融合多肽变体。
本公开的CYP153A-还原酶杂合融合多肽变体包含CYP153Aω-羟化酶结构域和P450RhF还原酶结构域。所述两个结构域的顺序不限于图5所示的顺序。所述CYP153Aω-羟化酶结构域可在N端处或可在所述杂合融合多肽变体的C端处。另外,所述P450RhF还原酶结构域可在N端处或可在所述杂合融合多肽变体的C端处。所述两个结构域可直接地或如图5所示通过连接体连接。在多个实施方案中,所述连接体为肽或多肽连接体。所述连接体的氨基酸序列的长度可凭经验或在结构信息的指导下或通过使用所述两种方法的组合来选择。所属领域的技术人员将认识到,长度或组成变化的多个所述序列可充当连接体,主要考虑到其既不过长又不过短。
本公开的CYP153A-还原酶杂合融合多肽变体包含如上文所提及的CYP153Aω-羟化酶结构域和P450RhF还原酶结构域。CYP153A-还原酶杂合融合多肽SEQ ID NO:6的氨基酸序列具有一种突变,即在位置307处的突变(G307A),其中丙氨酸(A)被甘氨酸(G)取代(即,被置换)。CYP153A-还原酶杂合融合多肽SEQ ID NO:38的氨基酸序列对应于CYP153A-还原酶杂合融合多肽SEQ ID NO:6的氨基酸序列,除了具有一种另外的突变,即在位置796处的突变(A796V),其中丙氨酸(A)被缬氨酸(V)取代(即,被置换)。
作为(模板)CYP153A-还原酶杂合融合多肽,可考虑杂合融合蛋白,其中CYP153AP450加氧酶与还原酶结构域融合以产生ω-羟基脂肪酸衍生物。自给自足的细胞色素P450加氧酶是其中还原酶搭配物融合至细胞色素P450催化蛋白的酶。一类自给自足的细菌细胞色素P450加氧酶由来自红球菌属NCIMB 9784(Roberts等人(2003)J.Biol.Chem.278:48914;Hunter等人(2005)FEBS Lett.579:2215)的P450RhF表示并且被称作“I类P450融合PFOR”(DeMot和Parret(2002)Trends Microbiol.10:502)。因此,作为(模板)CYP153A-还原酶杂合融合多肽,可考虑包含CYPl53A P450催化蛋白(例如,来自水油海杆菌)和来自红球菌属NCIMB9784的P450RhF的c端含FMN和Fe/S还原酶结构域的融合蛋白。
在本公开的多个实施方案中,所述杂合融合多肽变体为自给自足的并且具有ω-羟化酶酶活性,所述酶活性催化脂肪酸(衍生物)反应生成ω-OH脂肪酸或ω-OH脂肪酸衍生物。
一方面,本公开涵盖一种重组微生物或重组宿主细胞,所述微生物或重组宿主细胞用于当在来自可再生原料的碳源存在下在发酵液中生长时体内产生ω-OH脂肪酸或ω-OH脂肪酸衍生物,所述微生物具有经过工程改造以表达编码多肽的至少两个核酸序列的途径,所述多肽包括EC 3.1.2.-或EC 3.1.1.5或EC 3.1.2.14的硫酯酶;和CYP153A-还原酶杂合融合多肽变体,其中所述CYP153A-还原酶杂合融合多肽变体与SEQ ID NO:48、SEQ IDNO:50、SEQ ID NO:52、SEQ ID NO:54、SEQ ID NO:56SEQ ID NO:58、SEQ ID NO:60SEQ IDNO:62、SEQ ID NO:64、SEQ ID NO:66、SEQ ID NO:68、SEQ ID NO:70、SEQ ID NO:72、SEQ IDNO:74、SEQ ID NO:76、SEQ ID NO:78、SEQ ID NO:80、SEQ ID NO:82、SEQ ID NO:84、SEQ IDNO:86、SEQ ID NO:88、SEQ ID NO:90、SEQ ID NO:92、SEQ ID NO:94、SEQ ID NO:96、SEQ IDNO:98、SEQ ID NO:100、SEQ ID NO:102、SEQ ID NO:104、SEQ ID NO:106、SEQ ID NO:108、SEQ ID NO:110、SEQ ID NO:112、SEQ ID NO:114、SEQ ID NO:116、SEQ ID NO:118、SEQ IDNO:120、SEQ ID NO:122、SEQ ID NO:124、SEQ ID NO:126、SEQ ID NO:128、SEQ ID NO:130、SEQ ID NO:132、SEQ ID NO:134、SEQ ID NO:136、SEQ ID NO:138、SEQ ID NO:140、SEQ IDNO:142、SEQ ID NO:144、SEQ ID NO:146、SEQ ID NO:148、SEQ ID NO:150、SEQ ID NO:152、SEQ ID NO:154、SEQ ID NO:156、SEQ ID NO:158、SEQ ID NO:160、SEQ ID NO:162和SEQ IDNO:164中任一者具有至少90%、91%、93%、94%、95%、96%、97%、98%、99%或100%序列同一性。在一个实施方案中,所述CYP153A-还原酶杂合融合多肽变体为自给自足的CYP153A-RedRhF杂合融合蛋白变体。
本公开的另一方面提供一种细胞培养物,其包括如上文所论述(上文)的重组宿主细胞,其中所述细胞培养物产生ω-OH脂肪酸或其组合物。在一个实施方案中,所述细胞培养物产生ω-OH脂肪酸,包括C6、C7、C8、C9、C10、C11、C12、C13、C14、C15、C16、C17、C18、C19、C20、C8:1、C9:1、C10:1、C11:1、C12:1、C13:1、C14:1、C15:1、C16:1、C17:1、C18:1、C19:1和/或C20:1脂肪酸或脂肪酸衍生物或其组合物中的一者或多者。在一个实施方案中,所述细胞培养物产生不饱和ω-OHC16:1脂肪酸或其组合物。在另一实施方案中,所述细胞培养物产生饱和ω-OH C16脂肪酸或其组合物。在一个实施方案中,所述细胞培养物产生不饱和ω-OH C12:1脂肪酸或其组合物。在另一实施方案中,所述细胞培养物产生饱和ω-OH C12脂肪酸或其组合物。在一个实施方案中,所述细胞培养物产生不饱和ω-OH C14:1脂肪酸或其组合物。在另一实施方案中,所述细胞培养物产生饱和ω-OH C14脂肪酸或其组合物。在一个实施方案中,所述细胞培养物产生不饱和ω-OH C18:1脂肪酸或其组合物。在另一实施方案中,所述细胞培养物产生饱和ω-OH C18脂肪酸或其组合物。在一个实施方案中,所述细胞培养物产生不饱和ω-OH C10:1脂肪酸或其组合物。在另一实施方案中,所述细胞培养物产生饱和ω-OH C10脂肪酸或其组合物。在一个实施方案中,所述细胞培养物产生不饱和ω-OH C8:1脂肪酸或其组合物。在另一实施方案中,所述细胞培养物产生饱和ω-OH C8脂肪酸或其组合物。在一个实施方案中,所述细胞培养物产生不饱和ω-OH C20:1脂肪酸或其组合物。在另一实施方案中,所述细胞培养物产生饱和ω-OH C20脂肪酸或其组合物。在另一实施方案中,由所述重组宿主细胞产生另外的饱和或不饱和ω-OH脂肪酸或其组合物。
本公开的另一方面提供一种产生效价增加的ω-OH脂肪酸的方法,所述方法包括用碳源培养所述宿主细胞(上文);和收集ω-OH脂肪酸或其组合物。特别地,所述方法涵盖产生C6、C7、C8、C9、C10、C11、C12、C13、C14、C15、C16、C17、C18、C19、C20、C8:1、C9:1、C10:1、C11:1、C12:1、C13:1、C14:1、C15:1、C16:1、C17:1、C18:1、C19:1和/或C20:1脂肪酸或脂肪酸衍生物或其组合物。在一个实施方案中,所收集的ω-OH脂肪酸为不饱和ω-OH C16:1脂肪酸或其组合物。在另一实施方案中,所收集的ω-OH脂肪酸为饱和ω-OH C16脂肪酸或其组合物。在一个实施方案中,所收集的ω-OH脂肪酸为不饱和ω-OH C12:1脂肪酸或其组合物。在另一实施方案中,所收集的ω-OH脂肪酸为饱和ω-OH C12脂肪酸或其组合物。在一个实施方案中,所收集的ω-OH脂肪酸为不饱和ω-OH C14:1脂肪酸或其组合物。在另一实施方案中,所收集的ω-OH脂肪酸为饱和ω-OH C14脂肪酸或其组合物。在一个实施方案中,所收集的ω-OH脂肪酸为不饱和ω-OHC18:1脂肪酸或其组合物。在另一实施方案中,所收集的ω-OH脂肪酸为饱和ω-OH C18脂肪酸或其组合物。在一个实施方案中,所收集的ω-OH脂肪酸为不饱和ω-OH C10:1脂肪酸或其组合物。在另一实施方案中,所收集的ω-OH脂肪酸为饱和ω-OH C10脂肪酸或其组合物。在一个实施方案中,所收集的ω-OH脂肪酸为不饱和ω-OH C8:1脂肪酸或其组合物。在另一实施方案中,所收集的ω-OH脂肪酸为饱和ω-OH C8脂肪酸或其组合物。在一个实施方案中,所收集的ω-OH脂肪酸为不饱和ω-OH C20:1脂肪酸或其组合物。在另一实施方案中,所收集的ω-OH脂肪酸为饱和ω-OH C20脂肪酸或其组合物。在一个实施方案中,所收集的ω-OH脂肪酸为不饱和ω-OH C22:1脂肪酸或其组合物。在另一实施方案中,所收集的ω-OH脂肪酸为饱和ω-OH C22脂肪酸或其组合物。
附图简述
本公开当结合附图阅读时最好地理解,所述附图用于说明一些优选的实施方案。然而,应了解本公开不限于图中公开的具体实施方案。
图1是由于在重组微生物中表达所述CYP153A-还原酶杂合融合多肽变体和硫酯酶多肽而产生例如ω-羟基化C12脂肪酸(ω-OH C12FFA)和/或ω-羟基化C16:1脂肪酸(ω-OHC16:1FFA)的ω-羟基化脂肪酸衍生物的示例性生物合成途径的示意性概述。FAB是指微生物中的脂肪酸生物合成;fatB1是指来自加州桂(Umbellularia californica)(加州月桂(California bay))的中链酰基-ACP硫酯酶;并且fatA3是指来自拟南芥(Arabidopsisthaliana)的长链酰基-ACP硫酯酶。
图2提供由于CYP153A-还原酶杂合融合多肽变体的表达而产生ω-羟基化脂肪酸的一个实施例。为了说明通过变体产生ω-羟基化(ω-OH)脂肪酸,采用位点饱和诱变。所描绘的图示出了来自CYP153A(G307A,A796V)-Red450RhF的氨基酸位置141和309的位点饱和诱变的最佳命中(hit)。本图是指总的脂肪酸种类(总的FAS)(参看深灰色条);ω-羟基十六碳烯酸(ω-OH C16:1)(参看浅灰色条);和ω-羟基脂肪酸百分比(%ω-OH FFA)(参看箭头)。
图3示出了杂合细胞色素P450 Cyp153A(G307A)-RedRhF融合蛋白(SEQ ID NO:6)的多肽序列,其用作序列表A中所示的变体的模板序列。
图4示出了杂合细胞色素P450Cyp153A(G307A)-Red450RhF(A796V)融合蛋白(SEQID NO:38)的多肽序列,其用作序列表B中所示的变体的模板序列。
图5示出了细胞色素P450 Cyp153A(G307A)-RedRhF(A796V)杂合融合多肽变体SEQID NO:38的结构,其具有两个不同结构域,即通过连接体多肽连接的催化结构域和还原酶结构域。示出了所述催化结构域介于氨基酸位置1至486范围内并且包括介于氨基酸位置1至470范围内的P450 Cyp153A(G307A)和介于氨基酸位置471至486范围内的连接体多肽。作为Red450RhF(A796V)示出的所述还原酶结构域介于氨基酸位置487至799范围内。SEQ IDNO:38用作用于产生另外的变体的模板序列。
图6描绘了SEQ ID NO:98的三维蛋白结构。所述球描绘了突变型残基的碳、氮和氧原子。在中心附近还示出了在中间的铁原子周围成簇的血红素基团。所述潜在的配体结合位点作为灰显表面加以说明。如在这一图片上可见,所有突变型残基均在所述潜在的配体结合位点(即,活性位点)外部。
详述
一般概述
消除我们对石化产品的依赖性的一种方式是通过充当微型产生宿主的环境友好微生物产生如ω-OH脂肪酸衍生物的脂肪酸衍生物。所述细胞宿主(即,重组宿主细胞或微生物)经过工程改造以从如可再生原料的可再生来源(例如,发酵性碳水化合物、生物质、纤维素、甘油、CO、CO2等)产生ω-OH脂肪酸衍生物和双官能脂肪酸衍生物。这些ω-OH脂肪酸衍生物是用于工业产品(包括专用化学品、聚合物和香料)的原料。
本公开涉及当在重组宿主细胞中表达时引起ω-OH脂肪酸衍生物组合物的高效价、产率和/或生产率的ω-羟化酶相关的融合多肽,包括CYP153A-还原酶杂合融合多肽和其变体。本文中,增强的ω-OH脂肪酸衍生物生物合成是通过转化宿主细胞使得其表达CYP153A-还原酶杂合融合多肽或其变体而实现的,所述CYP153A-还原酶杂合融合多肽或其变体催化脂肪酸至ω-OH脂肪酸(例如ω-OH C6、C7、C8、C9、C10、C11、C12、C13、C14、C15、C16、C17、C18、C19、C20、C8:1、C9:1、C10:1、C11:1、C12:1、C13:1、C14:1、C15:1、C16:1、C17:1、C18:1、C19:1和/或C20:1脂肪酸或脂肪酸衍生物)的反应。本公开涵盖表达所述CYP153A-还原酶杂合融合多肽和其变体的重组宿主细胞或产生菌株。一方面,本公开涉及P450子家族cyp153A。
定义
如本说明书和随附权利要求书中所用,除非上下文另外清楚指示,否则单数形式“一(a)”、“一(an)”以及“所述(the)”包括多个提及物。因此,举例来说,对“宿主细胞”的提及包括两个或更多个所述宿主细胞,对“脂肪酯”的提及包括一种或多种脂肪酯,或酯的混合物,对“核酸序列”的提及包括一个或多个核酸序列,对“酶”的提及包括一种或多种酶等。
术语“酶分类(EC)编号”是指表示比酶活性的编号。EC编号在酶命名系统下根据酶催化的反应对酶分类。EC编号指定酶催化的反应。例如,如果来自不同生物的不同酶催化同一反应,那么其具有同一EC编号。另外,不同蛋白质折叠可催化同一反应并且因此将被指定同一EC编号(例如非同源同功酶,或NISE)。EC编号由国际生物化学与分子生物学联合会(IUBMB)的命名委员会确立,其描述可在万维网上的IUBMB酶命名网站获得。例如,细胞色素P450单加氧酶(P450)酶活性(包括ω-羟化酶或ω-加氧酶酶活性)被分类于EC 1.14.15.3下。属于P450酶家族的酶的功能性在大多数原核生物中从一个物种至下一物种是保守的。因此,不同微生物物种可实现被分类于EC 1.14.15.3下的相同酶活性。由EC 1.14.15.3表征的酶活性的实例为如本文所论述(上文)的CYP153A-还原酶杂合融合多肽或其变体的酶活性。
术语“ω-羟基化脂肪酸(omega-hydroxylated fatty acid)”或“ω-羟基化脂肪酸(ω-hydroxylated fatty acid)”或“ω-羟基脂肪酸(ω-hydroxy fatty acid)”或“ω-羟基脂肪酸(ω-hydroxyl fatty acid)”或“ω-OH脂肪酸”或“ωOH脂肪酸”在本文中可互换使用并且是指起源于脂肪酸代谢并且在omega(ω)位置处具有至少一个OH基团的脂肪酸。所述ω-羟基化脂肪酸的实例为C6、C7、C8、C9、C10、C11、C12、C13、C14、C15、C16、C17、C18、C19、C20、C8:1、C9:1、C10:1、C11:1、C12:1、C13:1、C14:1、C15:1、C16:1、C17:1、C18:1、C19:1和/或C20:1脂肪酸。在一个实施方案中,所述ω-羟基化脂肪酸为ω-OH C8:0脂肪酸、ω-OH C10:0脂肪酸、ω-OH C12:0脂肪酸、ω-OH C14:0脂肪酸、ω-OH C16:0脂肪酸、ω-OH C18:0脂肪酸、ω-OH C20:0脂肪酸、ω-OHC8:1脂肪酸、ω-OH C10:1脂肪酸、ω-OH C12:1脂肪酸、ω-OH C14:1脂肪酸、ω-OH C16:1脂肪酸、ω-OH C18:1脂肪酸、ω-OH C20:1脂肪酸等。在微生物中,所述ω-羟基化脂肪酸可用于产生ω-羟基化脂肪酸衍生物(如ω-羟基化脂肪酯)以及双官能脂肪酸衍生物(包括α,ω-二酸、α,ω-二酯和α,ω-二醇)。在这种意义上,术语“ω-羟基化脂肪酸衍生物(omega-hydroxylated fatty acid derivative)”和“ω-羟基化脂肪酸衍生物(ω-hydroxylatedfatty acid derivative)”和“ω-羟基脂肪酸衍生物(ω-hydroxy fatty acidderivative)”和“ω-羟基脂肪酸衍生物(ω-hydroxyl fatty acid derivative)”和“α,ω-双官能脂肪酸衍生物”和“ω-OH脂肪酸衍生物”是指起源于脂肪酸代谢并且在ω位置处具有至少一个OH基团或来源于在ω位置处具有至少一个OH基团的中间物的化学实体。本文中,“omega(ω)位置”是指脂肪酸衍生物中在关于其伯官能团的相对端的末端碳原子。所述ω-羟基化脂肪酸衍生物包括但不限于α,ω-二酸;α,ω-二酯;α,ω-二醇和其衍生的化学品(例如,大环内酯)。
如本文所提及的“ω-羟基化脂肪酸组合物”或“ω-OH脂肪酸组合物”是由重组宿主细胞产生并且典型地包括具有多种链长和/或饱和度和/或分支特征的某些类型的ω-羟基化脂肪酸的混合物。同样,“ω-羟基化脂肪酸衍生物组合物”是由重组宿主细胞产生并且典型地包括具有多种链长和/或饱和度和/或分支特征的某些类型的ω-羟基化脂肪酸衍生物(例如,具有多种链长和/或饱和度和/或分支特征的ω-羟基化脂肪酸;具有多种链长和/或饱和度和/或分支特征的ω-羟基化脂肪酯;具有多种链长和/或饱和度和/或分支特征的α,ω-二酸;具有多种链长和/或饱和度和/或分支特征的α,ω-二酯;具有多种链长和/或饱和度和/或分支特征的α,ω-二醇;等)的混合物。在一些情况下,所述ω-OH脂肪酸衍生物组合物主要包括一种类型的ω-OH脂肪酸衍生物,例如1,12-十二碳烯二醇、或1,14-十四烷二醇、或16-羟基十六烷酸甲酯、或16-羟基十六碳烯酸、或15-羟基十五烷酸、或15-羟基十五碳烯酸或18-羟基十八碳烯酸,或这些脂肪酸衍生物中任一者的甲酯,或其它。在其它情况下,所述ω-OH脂肪酸衍生物组合物包括超过一种类型的ω-OH脂肪酸衍生物的混合物以便提供具体设计的组合物(例如,同一组合物中约20%12-羟基十二烷酸和约80%1,14-14-羟基十四烷酸将提供所述实例)。
术语“登录号”或“NCBI登录号”或“GenBank登录号”是指表示具体核酸序列的编号。在本说明书中论述的序列登录号是获自由美国国立卫生研究院维持的美国国家生物技术信息中心(NCBI;National Center for Biotechnology Information)所提供的数据库和获自由瑞士生物信息研究所提供的UniProt Knowledgebase(UniProtKB)和Swiss-Prot数据库(还称作UniProtKB登录号)。
如本文所用,术语“核苷酸”是指由杂环碱基、糖和一个或多个磷酸基团组成的多核苷酸的单体单元。天然存在的碱基(鸟嘌呤(G)、腺嘌呤(A)、胞嘧啶(C)、胸腺嘧啶(T)和尿嘧啶(U))典型地为嘌呤或嘧啶的衍生物,不过应了解还包括天然和非天然存在的碱基类似物。天然存在的糖为戊糖(五碳糖)脱氧核糖(其形成DNA)或核糖(其形成RNA),不过应了解还包括天然和非天然存在的糖类似物。核酸典型地经由磷酸酯键连接以形成核酸或多核苷酸,不过所属领域中已知多种其它键联(例如硫代磷酸酯、硼烷磷酸酯等)。
术语“多核苷酸”是指核糖核苷酸(RNA)或脱氧核糖核苷酸(DNA)的聚合物,其可为单链的或双链的并且其可含有非天然或改变的核苷酸。术语“多核苷酸”、“核酸序列”和“核苷酸序列”在本文中可互换使用以指任何长度的核苷酸(RNA或DNA)的聚合物形式。这些术语是指所述分子的一级结构,并且因此包括双链和单链DNA,和双链和单链RNA。所述术语包括由核苷酸类似物和经过修饰的多核苷酸(如但不限于甲基化和/或加帽多核苷酸)制得的RNA或DNA的类似物作为相等物。所述多核苷酸可呈任何形式,包括但不限于质粒、病毒、染色体、EST、cDNA、mRNA和rRNA。
如本文所用,术语“多肽”和“蛋白质”可互换使用以指氨基酸残基的聚合物。术语“重组多肽”是指通过重组技术产生的多肽,其中一般说来将编码所表达的蛋白质的DNA或RNA插入至合适的表达载体中,所述表达载体又用于转化宿主细胞以产生所述多肽。同样,术语“重组多核苷酸”或“重组核酸”或“重组DNA”通过本领域技术人员已知的重组技术产生。
术语“同系物”和“同源的”是指包含与相应的多核苷酸或多肽序列具有至少约百分之50(%)同一性的序列的多核苷酸或多肽。优选地,同源多核苷酸或多肽具有与相应的氨基酸序列或多核苷酸序列具有至少约80%、81%、82%、83%、84%、85%、86%、87%、88%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%或至少约99%同源性的多核苷酸序列或氨基酸序列。如本文所用,术语序列“同源性”和序列“同一性”可互换使用。本领域技术人员充分了解确定两个或更多个序列之间的同源性的方法。简单地说,两个序列之间的“同源性”的计算可如下执行。所述序列出于最佳比较目的进行比对(例如,针对最佳比对可在第一和第二氨基酸或核酸序列中的一者或两者中引入空位并且出于比较目的可忽略非同源序列)。在一个优选实施方案中,出于比较目的进行比对的第一序列的长度为第二序列的长度的至少约30%、优选地至少约40%、更优选地至少约50%、甚至更优选地至少约60%并且甚至更优选地至少约70%、至少约80%、至少约85%、至少约90%、至少约95%、至少约98%或约100%。接着比较在所述第一和第二序列的相应氨基酸位置或核苷酸位置处的氨基酸残基或核苷酸。当所述第一序列中的位置由与所述第二序列中的相应位置相同的氨基酸残基或核苷酸占据时,则所述分子在所述位置处为同一的。两个序列之间的同源性百分比是由所述序列共享的同一位置的数目的函数,考虑为了所述两个序列的最佳比对需要引入的空位的数目和各空位的长度。序列的比较和两个序列之间的同源性百分比的确定可使用数学算法实现,如BLAST(Altschul等人(1990)J.Mol.Biol.215(3):403-410)。两个氨基酸序列之间的同源性百分比也可使用已经并入GCG软件包中的GAP程序中的Needleman和Wunsch算法,使用Blossum 62矩阵或PAM250矩阵和空位权重16、14、12、10、8、6或4和长度权重1、2、3、4、5或6来确定(Needleman和Wunsch(1970)J.Mol.Biol.48:444-453)。两个核苷酸序列之间的同源性百分比也可使用GCG软件包中的GAP程序,使用NWSgapdna.CMP矩阵和空位权重40、50、60、70或80和长度权重1、2、3、4、5或6来确定。本领域技术人员可执行初始同源性计算并且相应地调节算法参数。参数的优选集合(和如果从业者未确定哪些参数应该应用于确定分子是否在权利要求书的同源性限制内,那么应该使用的参数)是Blossum 62计分矩阵,其具有空位罚分12、空位延伸罚分4和移码空位罚分5。序列比对的另外方法是生物技术领域中已知的(参看例如Rosenberg(2005)BMCBioinformatics 6:278;Altschul等人(2005)FEBS J.272(20):5101-5109)。
术语“在低严格度、中等严格度、高严格度或极高严格度条件下杂交”描述了用于杂交和洗涤的条件。关于执行杂交反应的指导可在Current Protocols in MolecularBiology,John Wiley&Sons,N.Y.(1989),6.3.1-6.3.6中找到。水性和非水性方法描述于所述参考文献中并且可使用任一方法。本文所提及的具体杂交条件如下:(1)低严格度杂交条件--6X氯化钠/柠檬酸钠(SSC)在约45℃下,随后至少在50℃下在0.2X SSC、0.1%SDS中进行两次洗涤(对于低严格度条件所述洗涤的温度可增加至55℃);(2)中等严格度杂交条件--6X SSC在约45℃下,随后在60℃下在0.2X SSC、0.1%SDS中进行一次或多次洗涤;(3)高严格度杂交条件--6X SSC在约45℃下,随后在65℃下在0.2.X SSC、0.1%SDS中进行一次或多次洗涤;和(4)极高严格度杂交条件--0.5M磷酸钠、7%SDS在65℃下,随后在65℃下在0.2X SSC、1%SDS中进行一次或多次洗涤。除非另外规定,否则极高严格度条件(4)为优选条件。
“内源”多肽是指由亲本细胞(或宿主细胞)的基因组编码或在所述亲本宿主细胞内部起源或产生或出现的多肽。“外源”多肽是指不是由亲本细胞的基因组编码或在所述亲本宿主细胞外部起源的多肽。变体或突变型多肽是外源多肽的实例。因此,非天然存在的核酸分子一旦被引入细胞中即被视为对细胞来说外源性的。天然存在的核酸分子对特定细胞来说也可为外源性的。例如,一旦从细胞X分离的完整编码序列被引入细胞Y中,即使X和Y为相同细胞类型,所述编码序列关于细胞Y也是外源核酸。
术语“过表达的”意指使基因以与针对所述基因的野生型或原生或内源转录速率相比升高的速率转录。在一些实例中,过表达另外包括与针对所述基因的野生型或原生或内源翻译速率相比所述基因的升高的翻译速率。测试过表达的方法是所属领域中众所周知的,例如转录的RNA水平可使用rtPCR来评估并且蛋白质水平可使用SDS page凝胶分析来评估。
术语“异源”意指来源于不同生物、不同细胞类型或不同物种。如本文所用,其是指非天然存在于给定生物中的核苷酸、多核苷酸、多肽或蛋白质序列。例如,蓝细菌的原生多核苷酸序列可通过重组方法引入至大肠杆菌的宿主细胞中,并且来自蓝细菌的多核苷酸接着对大肠杆菌细胞(例如重组细胞)来说为异源性的。术语“异源”也可关于以非原生状态存在于重组宿主细胞中的核苷酸、多核苷酸、多肽或蛋白质序列使用。例如,“异源”核苷酸、多核苷酸、多肽或蛋白质序列可相对于天然存在于相应野生型宿主细胞中的野生型序列进行修饰,例如表达水平或核苷酸、多核苷酸、多肽或蛋白质的序列的修饰。
如本文所用,术语多肽的“片段”是指全长多肽或蛋白质中大小介于两个氨基酸残基至完整氨基酸序列减去一个氨基酸残基的范围内的较短部分。在本公开的某些实施方案中,片段是指多肽或蛋白质的结构域(例如,底物结合结构域或催化结构域)的完整氨基酸序列。
术语“诱变”是指使生物的遗传信息以稳定方式改变的过程。蛋白编码核酸序列的诱变产生突变蛋白质。诱变也指非编码核酸序列的改变,所述改变产生经过修饰的蛋白质活性。
如本文所用,“突变”是指基因的核酸位置中的永久改变或多肽或蛋白中的氨基酸位置中的永久改变。突变包括取代、添加、插入和缺失。例如,氨基酸位置中的突变可为一种类型的氨基酸被另一类型的氨基酸取代(例如,丝氨酸(S)可被丙氨酸(A)取代;赖氨酸(L)可被苏氨酸(T)取代;等)。因而,多肽或蛋白质可具有一种或多种突变,其中一种氨基酸被另一氨基酸取代。由本公开提供的CYP153A-还原酶杂合融合多肽变体在氨基酸序列SEQ IDNO:38中的特定氨基酸位置处具有突变。例如,本公开提供一种CYP153A-还原酶杂合融合多肽变体,其在氨基酸位置SEQ ID NO:38的12、27、119、140、157、159、233和244中的每一者处具有突变。在这些特定氨基酸位置中的每一者处具有突变的所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-羟基化脂肪酸。优选地,当与例如SEQ ID NO:38的CYP153A-还原酶杂合融合多肽相比时,在这些特定氨基酸位置中的每一者处具有突变的所述CYP153A-还原酶杂合融合多肽变体可以较高效价产生ω-OH脂肪酸衍生物。因此,在所要求的CYP153A-还原酶杂合融合多肽变体的特定氨基酸位置处的突变优选地不包括如下突变,当与例如SEQ ID NO:38的CYP153A-还原酶杂合融合多肽相比时,所述突变可不提供所要求的以较高效价产生ω-OH脂肪酸衍生物的效应。本公开的CYP153A-还原酶杂合融合多肽变体可使用所属领域中已知的方法针对其功能进行筛选,如与野生型CYP153A多肽或模板CYP153A-还原酶杂合融合多肽或任何其它参考CYP153A-还原酶杂合融合多肽相比经过改进的功能,包括但不限于增加的催化活性、增加的稳定性或减少的抑制(例如,减少的反馈抑制)。在本公开的多个实施方案中,在权利要求书中定义的在特定位置处的突变具有所述性质,即如与例如SEQ ID NO:38的CYP153A-还原酶杂合融合多肽相比,其提供增加量的ω-羟基脂肪酸(ω-OH FFA效价),和/或增加的脂肪酸至ω-羟基脂肪酸的转化。在多个实施方案中,在权利要求书中定义的在特定位置处的突变具有所述性质,即如与例如SEQ ID NO:42或SEQ ID NO:46的CYP153A-还原酶杂合融合多肽相比,其提供增加的ω-羟基脂肪酸的量(ω-OH FFA效价),和/或增加的脂肪酸至ω-羟基脂肪酸的转化。在多个实施方案中,在权利要求书中定义的在特定位置处的突变具有所述性质,即如与例如SEQ ID NO:98的CYP153A-还原酶杂合融合多肽相比,其提供增加的ω-羟基脂肪酸的量(ω-OH FFA效价),和/或增加的脂肪酸至ω-羟基脂肪酸的转化。在本公开的多个实施方案中,在权利要求书中定义的在特定位置处的突变中的一者或多者意指一种或多种氨基酸取代和/或缺失。优选地,在权利要求书中定义的在特定位置处的突变中的一者或多者意指一种或多种氨基酸取代。更优选地,在权利要求书中针对给定的CYP153A-还原酶杂合融合多肽变体定义的在特定位置处的全部突变均为氨基酸取代。如果在某一位置处的氨基酸残基缺失,并且不同的氨基酸残基被插入所述位置处,那么这可被视为在某一位置处的氨基酸残基的取代。在本公开的多个实施方案中,在氨基酸位置处的突变意指氨基酸取代(在所述位置处),其中所述取代并非沉默取代。
如本文所用,术语“基因”是指编码RNA产物或蛋白产物的核酸序列,以及影响所述RNA或蛋白质的表达的可操作性连接的核酸序列(例如,所述序列包括但不限于启动子或增强子序列)或编码影响所述RNA或蛋白质的表达的序列的可操作性连接的核酸序列(例如,所述序列包括但不限于核糖体结合位点或翻译控制序列)。
表达控制序列是所属领域中已知的并且包括例如启动子、增强子、聚腺苷酸化信号、转录终止子、内部核糖体进入位点(IRES)等,其提供宿主细胞中多核苷酸序列的表达。表达控制序列特异性地与牵涉于转录中的细胞蛋白质相互作用(Maniatis等人(1987)Science 236:1237-1245)。示例性表达控制序列描述于例如Goeddel,Gene ExpressionTechnology:Methods in Enzymology,第185卷,Academic Press,San Diego,Calif.(1990)中。在本公开的方法中,表达控制序列可操作性连接于多核苷酸序列。“可操作性连接”意指多核苷酸序列和表达控制序列以一定方式连接以便当适当分子(例如,转录活化因子蛋白)结合于所述表达控制序列时允许基因表达。可操作性连接的启动子就转录和翻译的方向来说位于所选择的多核苷酸序列的上游。可操作性连接的增强子可位于所选择的多核苷酸的上游、内部或下游。
如本文所用,术语“载体”是指能够转运已经与其连接的另一核酸(即,多核苷酸序列)的核酸分子。一种类型的适用载体是附加体(即,能够在染色体外复制的核酸)。适用的载体是能够自主复制和/或表达与其连接的核酸的那些。能够指导与其可操作性连接的基因的表达的载体在本文中称作“表达载体。”一般来说,可用于重组DNA技术的表达载体通常呈“质粒”的形式,所述质粒一般指圆形双链DNA环,所述环在其呈载体形式时不结合于染色体。其它适用的表达载体以线性形式提供。还包括表达载体的所述其它形式,其发挥相等功能并且随后关于这一点在所属领域中已知。在一些实施方案中,重组载体进一步包括可操作性连接于多核苷酸序列的启动子。在一些实施方案中,所述启动子为发育调控的启动子、细胞器特异性启动子、组织特异性启动子、诱导型启动子、组成型启动子或细胞特异性启动子。所述重组载体典型地包含选自以下的至少一个序列:可操作性偶合于多核苷酸序列的表达控制序列;可操作性偶合于多核苷酸序列的选择标记;可操作性偶合于多核苷酸序列的标记序列;可操作性偶合于多核苷酸序列的纯化部分;可操作性偶合于多核苷酸序列的分泌序列;和可操作性偶合于多核苷酸序列的靶向序列。在某些实施方案中,所述核苷酸序列稳定性并入宿主细胞的基因组DNA中,并且所述核苷酸序列的表达在经调控的启动子区域的控制下。如本文所用的表达载体包括如本文所述的呈适用于多核苷酸序列在宿主细胞中的表达的形式的特定多核苷酸序列。本领域技术人员应了解,所述表达载体的设计可取决于待转化的宿主细胞的选择、所需多肽的表达水平等的因素。本文所述的表达载体可引入宿主细胞中以产生由如本文所述的多核苷酸序列编码的多肽,包括融合多肽。编码多肽的基因在例如大肠杆菌的原核生物中的表达最通常用含有组成型或诱导型启动子的载体进行,所述启动子指导融合或非融合多肽的表达。融合载体将多个氨基酸添加至其中编码的多肽,通常至所述重组多肽的氨基或羧基端。所述融合载体典型地用于以下三种目的中的一者或多者,包括增加重组多肽的表达;增加重组多肽的溶解度;和通过充当亲和纯化中的配体来帮助纯化重组多肽。通常,在融合表达载体中,蛋白水解裂解位点被引入融合部分与重组多肽的接合点处。这使得能够在融合多肽的纯化后分离重组多肽与融合部分。在某些实施方案中,本公开的多核苷酸序列可操作性连接于来源于噬菌体T5的启动子。
在某些实施方案中,宿主细胞为酵母细胞,并且表达载体为酵母表达载体。用于酵母酿酒酵母(S.cerevisiae)中的表达的载体的实例包括pYepSec1(Baldari等人(1987)EMBO J.6:229-234);pMFa(Kurjan等人(1982)Cell 30:933-943);pJRY88(Schultz等人(1987)Gene 54:113-123);pYES2(Invitrogen Corp.,San Diego,CA),和picZ(InvitrogenCorp.,San Diego,CA)。在其它实施方案中,宿主细胞为昆虫细胞,并且表达载体为杆状病毒表达载体。可用于培养的昆虫细胞(例如Sf9细胞)中蛋白质的表达的杆状病毒载体包括例如pAc系列(Smith等人(1983)Mol.Cell Biol.3:2156-2165)和pVL系列(Lucklow等人(1989)Virology 170:31-39)。在另一实施方案中,本文所述的多核苷酸序列可在哺乳动物细胞中使用哺乳动物表达载体表达。用于原核和真核细胞的其它合适表达系统是所属领域中众所周知的;参看例如Sambrook等人,“Molecular Cloning:A Laboratory Manual,”第二版,Cold Spring Harbor Laboratory,(1989)。
如本文所用,术语“CoA”或“酰基-CoA”是指在烷基链的羰基碳与辅酶A(CoA)的4’-磷酸泛酰巯基乙胺基(4’-phosphopantethionyl)部分的巯基之间形成的酰基硫酯,其具有式R-C(O)S-CoA,其中R为具有至少4个碳原子的任何烷基。
术语“ACP”意指酰基载体蛋白。ACP是在脂肪酸生物合成期间的酰基中间物的高度保守载体,其中生长中的链在合成期间作为硫醇酯结合于4’-磷酸泛酰巯基乙胺部分的远端硫醇处。所述蛋白质以两种形式存在,即apo-ACP(在脂肪酸生物合成中无活性)和ACP或holo-ACP(在脂肪酸生物合成中具活性)。术语“ACP”和“holo-ACP”在本文中可互换使用并且是指所述蛋白质的活性形式。被称为磷酸泛酰巯基乙胺转移酶的酶牵涉于无活性apo-ACP至活性holo-ACP的转化中。更具体说来,ACP以无活性apo-ACP形式表达并且4’-磷酸泛酰巯基乙胺部分必须通过holo-酰基载体蛋白合酶(ACPS;磷酸泛酰巯基乙胺转移酶)的作用翻译后连接于所述ACP上的保守丝氨酸残基,以便产生holo-ACP。
如本文所用,术语“酰基-ACP”是指烷基链的羰基碳与酰基载体蛋白(ACP)的磷酸泛酰巯基乙胺基部分的巯基之间形成的酰基硫酯。在一些实施方案中,ACP为完全饱和的酰基-ACP的合成中的中间物。在其它实施方案中,ACP为不饱和的酰基-ACP的合成中的中间物。在一些实施方案中,碳链将具有约5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25或26个碳。
如本文所用,术语“脂肪酸衍生物”意指“脂肪酸”或“脂肪酸衍生物”,其可称作“脂肪酸或其衍生物”。术语“脂肪酸”意指具有式RCOOH的羧酸。R表示脂肪族基团,优选地烷基。R可包括介于约4个与约22个之间的碳原子。脂肪酸可为饱和、单不饱和或多不饱和的。“脂肪酸衍生物”是部分地由生产宿主生物(例如,重组宿主细胞或微生物)的脂肪酸生物合成途径制得的产物。“脂肪酸衍生物”包括部分地由ACP、酰基-ACP或酰基-ACP衍生物制得的产物。示例性脂肪酸衍生物包括例如酰基-CoA、脂肪酸、脂肪醛、短链和长链醇、脂肪醇、烃、酯(例如,蜡、脂肪酸酯或脂肪酯)、末端烯烃、内部烯烃、酮以及ω-OH脂肪酸和其ω-OH脂肪酸衍生物(包括α,ω-二酸)和其它双官能化合物。
如本文所用,术语“脂肪酸生物合成途径”意指产生脂肪酸和其衍生物的生物合成途径。所述脂肪酸生物合成途径可包括另外的酶以产生具有所需特征的脂肪酸衍生物。
脂肪酸的R基团可为直链或支链。支链可具有超过一个分支点并且可包括环状分支。在一些实施方案中,支链脂肪酸为C6、C7、C8、C9、C10、C11、C12、C13、C14、C15、C16、C17、C18、C19、C20、C21、C22、C23、C24、C25或C26支链脂肪酸。在其它实施方案中,支链脂肪酸为C6、C8、C10、C12、C13、C14、C15、C16、C17、C18或C20支链脂肪酸。在某些实施方案中,支链脂肪酸的羟基(OH)在omega(ω)位置中。在某些实施方案中,支链脂肪酸为异脂肪酸或反异脂肪酸。在示例性实施方案中,支链脂肪酸选自异-C7:0-、异-C8:0-、异-C9:0-、异-C10:0-、异-C11:0-、异-C12:0-、异-C13:0-、异-C14:0-、异-C15:0-、异-C16:0-、异-C17:0-、异-C18:0-、异-C19:0-、异-C20:0、反异-C7:0-、反异-C9:0-、反异-C11:0-、反异-C13:0-、反异-C15:0-、反异-C17:0-和反异-C19:0支链脂肪酸。
脂肪酸的R基团可为饱和或不饱和的。如果不饱和,那么所述R基团可具有一个或超过一个不饱和点。在一些实施方案中,不饱和脂肪酸为单不饱和脂肪酸。在某些实施方案中,所述不饱和脂肪酸为C8:1-、C9:1-、C10:1-、C11:1-、C12:1-、C13:1-、C14:1-、C15:1-、C16:1-、C17:1-、C18:1-、C19:1-、C20:1-、C21:1-、C22:1-、C23:1-、C24:1-、C25:1-或C26:1不饱和脂肪酸。在某些实施方案中,所述不饱和脂肪酸为C8:1、C10:1、C12:1、C14:1、C16:1、C18:1或C20:1。在其它实施方案中,所述不饱和脂肪酸在ω-7位置处不饱和。在某些实施方案中,所述不饱和脂肪酸具有顺式双键。
如本文所用,“重组宿主细胞”或“经过工程改造的宿主细胞”为已经进行修饰使得其产生ω-羟基化脂肪酸和ω-羟基化脂肪酸衍生物(包括双官能脂肪酸衍生物)的宿主细胞,例如微生物。在一些实施方案中,所述重组宿主细胞包含一种或多种多核苷酸,各多核苷酸编码具有ω-羟化酶生物合成酶活性的CYP153A-还原酶杂合融合多肽或其变体,其中所述重组宿主细胞当在碳源存在下在有效表达所述多核苷酸的条件下培养时产生ω-羟基化脂肪酸和/或ω-羟基化脂肪酸衍生物或其组合物。
如本文所用,术语“克隆”典型地是指从单一共同祖先遗传并且基本上与所述祖先遗传学同一的细胞或细胞群,例如从单一细菌细胞产生的克隆细菌菌落的细菌。
如本文所用,术语“培养物”典型地是指包含活细胞的液体培养基。在一个实施方案中,培养物包含在预先确定的培养基中在受控条件下繁殖的细胞,例如在包含所选择的碳源和/或氮的液体培养基中生长的重组宿主细胞的培养物。
术语“培养”或“培育”是指使细胞(例如,微生物细胞)的群体在液体或固体培养基中在合适条件下生长。在特定实施方案中,培养是指底物至最终产物的发酵性生物转化。培养基是众所周知的并且所述培养基的个别组分可获自商业来源,例如DIFCO培养基和BBL培养基。在一个非限制性实例中,水性营养培养基是包含氮、盐和碳的复合来源的“丰富培养基”,如YP培养基,其包含10g/L的蛋白胨和10g/L的所述培养基的酵母提取物。另外,宿主细胞可根据描述于例如美国专利5,000,000;5,028,539;5,424,202;5,482,846;5,602,030和WO2010127318中的方法进行工程改造以有效地吸收碳并且使用纤维素材料作为碳源。另外,宿主细胞可经过工程改造以表达转化酶,使得蔗糖可用作碳源。
如本文所用,术语“在有效表达所述异源核苷酸序列的条件下”意指允许宿主细胞产生所需脂肪酸衍生物(例如,ω-OH脂肪酸和/或ω-OH脂肪酸衍生物)的任何条件。合适条件包括例如发酵条件。
如本文所用,重组宿主细胞中蛋白质(例如酶)的“经过修饰”或“改变的水平”的活性是指相对于亲本或原生宿主细胞确定的活性的一种或多种特征的差异。典型地,活性的差异在具有经过修饰的活性的重组宿主细胞与相应的野生型宿主细胞之间确定(例如,重组宿主细胞的培养物相对于野生型宿主细胞的比较)。经过修饰的活性可为例如由重组宿主细胞表达的蛋白质的经过修饰的量(例如,由于编码所述蛋白质的DNA序列的拷贝的增加或降低的数目、编码所述蛋白质的mRNA转录物的增加或降低的数目和/或由mRNA翻译所述蛋白质的增加或降低的量);所述蛋白质的结构的改变(例如一级结构的改变,如引起底物特异性的改变的所述蛋白质的编码序列的改变,所观察到的动力学参数的改变);和蛋白稳定性的改变(例如,所述蛋白质的增加或降低的降解)的结果。在一些实施方案中,所述多肽是任何本文所述的多肽的突变体或变体。在某些情况下,对如本文所述的多肽的编码序列针对在特定宿主细胞中的表达进行密码子优化。例如,对于在大肠杆菌中的表达,一个或多个密码子可进行优化(Grosjean等人(1982)Gene 18:199-209)。
如本文所用的术语“调控序列”典型地是指可操作性连接于编码蛋白质的DNA序列的DNA中碱基的序列,其最终控制所述蛋白质的表达。调控序列的实例包括但不限于RNA启动子序列、转录因子结合序列、转录终止序列、转录调节剂(如增强子元件)、影响RNA稳定性的核苷酸序列和翻译调控序列(如核糖体结合位点(例如在原核生物中的Shine-Dalgarno序列或在真核生物中的Kozak序列)、起始密码子、终止密码子)。
如本文所用,措辞“所述核苷酸序列的表达相对于野生型核苷酸序列经过修饰”意指内源核苷酸序列的表达水平和/或活性或异源或非原生多肽编码核苷酸序列的表达和/或活性的增加或降低。
如本文所用,措辞“CYP153A-还原酶杂合融合多肽序列变体的活性相对于CYP153A-还原酶杂合融合多肽序列”(即,多肽模板)的活性经过修饰意指与表达的多肽序列模板相比表达的多肽序列变体的活性水平的增加或降低。所述多肽模板由核酸模板(即,DNA模板序列)编码。多肽序列模板的实例为杂合cyp153A-RedRhF融合蛋白序列,其中cyp153A与还原酶结构域融合。多肽序列模板的另一实例为SEQ ID NO:6。多肽序列模板的另一实例为SEQ ID NO:38。任何多肽序列均可用作模板,包括变体。
如本文所用,关于多核苷酸的术语“表达”是使其发挥作用。编码多肽(或蛋白质)的多核苷酸当表达时将被转录和翻译以产生所述多肽(或蛋白质)。如本文所用,术语“过表达”意指在细胞中以大于相应野生型细胞中在相同条件下通常所表达的浓度表达(或引起表达)多核苷酸或多肽。在另一实施方案中,术语“过表达”意指在细胞中以大于表达模板多核苷酸或模板多肽序列的相应细胞中在相同条件下通常所表达的浓度表达(或引起表达)多核苷酸或多肽。模板多肽序列的实例为CYP153A-RedRhF-杂合融合多肽。
术语“改变的表达水平”和“经过修饰的表达水平”可互换使用并且意指多核苷酸、多肽或脂肪酸衍生物如与其在相同条件下在相应野生型细胞中的浓度相比以不同浓度存在于经过工程改造的宿主细胞中。
如本文所用,术语“效价”是指每单位体积的宿主细胞培养物所产生的ω-OH脂肪酸和/或ω-OH脂肪酸衍生物的量。在本文所述的组合物和方法的任何方面,ω-OH脂肪酸和/或ω-OH脂肪酸衍生物以约25mg/L、约50mg/L、约75mg/L、约100mg/L、约125mg/L、约150mg/L、约175mg/L、约200mg/L、约225mg/L、约250mg/L、约275mg/L、约300mg/L、约325mg/L、约350mg/L、约375mg/L、约400mg/L、约425mg/L、约450mg/L、约475mg/L、约500mg/L、约525mg/L、约550mg/L、约575mg/L、约600mg/L、约625mg/L、约650mg/L、约675mg/L、约700mg/L、约725mg/L、约750mg/L、约775mg/L、约800mg/L、约825mg/L、约850mg/L、约875mg/L、约900mg/L、约925mg/L、约950mg/L、约975mg/L、约1000mg/L、约1050mg/L、约1075mg/L、约1100mg/L、约1125mg/L、约1150mg/L、约1175mg/L、约1200mg/L、约1225mg/L、约1250mg/L、约1275mg/L、约1300mg/L、约1325mg/L、约1350mg/L、约1375mg/L、约1400mg/L、约1425mg/L、约1450mg/L、约1475mg/L、约1500mg/L、约1525mg/L、约1550mg/L、约1575mg/L、约1600mg/L、约1625mg/L、约1650mg/L、约1675mg/L、约1700mg/L、约1725mg/L、约1750mg/L、约1775mg/L、约1800mg/L、约1825mg/L、约1850mg/L、约1875mg/L、约1900mg/L、约1925mg/L、约1950mg/L、约1975mg/L、约2000mg/L(2g/L)、3g/L、5g/L、10g/L、20g/L、30g/L、40g/L、50g/L、60g/L、70g/L、80g/L、90g/L、100g/L或由前述值中的任何两者界定的范围的效价产生。在其它实施方案中,ω-OH脂肪酸和/或ω-OH脂肪酸衍生物以超过100g/L、超过200g/L、超过300g/L或更高,如500g/L、700g/L、1000g/L、1200g/L、1500g/L或2000g/L的效价产生。在一个实施方案中,根据本公开的方法由重组宿主细胞产生的ω-OH脂肪酸和/或ω-OH脂肪酸衍生物的效价为5g/L至200g/L、10g/L至150g/L、20g/L至120g/L、25g/L至110g/L和30g/L至100g/L。
如本文所用,术语“由宿主细胞产生的ω-OH脂肪酸和/或ω-OH脂肪酸衍生物的产率”是指输入碳源在宿主细胞中转化为产物(即,ω-OH脂肪酸和/或ω-OH脂肪酸衍生物)的效率。根据本公开的方法经过工程改造以产生ω-OH脂肪酸和/或ω-OH脂肪酸衍生物的宿主细胞具有至少3%、至少4%、至少5%、至少6%、至少7%、至少8%、至少9%、至少10%、至少11%、至少12%、至少13%、至少14%、至少15%、至少16%、至少17%、至少18%、至少19%、至少20%、至少21%、至少22%、至少23%、至少24%、至少25%、至少26%、至少27%、至少28%、至少29%或至少30%或由前述值中的任何两者界定的范围的产率。在其它实施方案中,ω-OH脂肪酸和/或ω-OH脂肪酸衍生物以超过30%、40%、50%、60%、70%、80%、90%或更高的产率产生。或者或另外,所述产率为约30%或更低、约27%或更低、约25%或更低或约22%或更低。因此,所述产率可由以上终点中的任何两者界定。例如,根据本公开的方法由重组宿主细胞产生的ω-OH脂肪酸和/或ω-OH脂肪酸衍生物的产率可为5%至15%、10%至25%、10%至22%、15%至27%、18%至22%、20%至28%、20%至30%、25%至40%或更大。根据本公开的方法由重组宿主细胞产生的ω-OH脂肪酸和/或ω-OH脂肪酸衍生物的优选产率的实例为10%至30%。根据本公开的方法由重组宿主细胞产生的ω-OH脂肪酸和/或ω-OH脂肪酸衍生物的优选产率的另一实例为10%至40%。根据本公开的方法由重组宿主细胞产生的ω-OH脂肪酸和/或ω-OH脂肪酸衍生物的优选产率的另一实例为10%至50%。
如本文所用,术语“生产率”是指每单位时间每单位体积的宿主细胞培养物所产生的ω-OH脂肪酸和/或ω-OH脂肪酸衍生物的量。在本文所述的组合物和方法的任何方面,由重组宿主细胞产生的ω-OH脂肪酸和/或ω-OH脂肪酸衍生物的生产率为至少100mg/L/小时、至少200mg/L/小时0、至少300mg/L/小时、至少400mg/L/小时、至少500mg/L/小时、至少600mg/L/小时、至少700mg/L/小时、至少800mg/L/小时、至少900mg/L/小时、至少1000mg/L/小时、至少1100mg/L/小时、至少1200mg/L/小时、至少1300mg/L/小时、至少1400mg/L/小时、至少1500mg/L/小时、至少1600mg/L/小时、至少1700mg/L/小时、至少1800mg/L/小时、至少1900mg/L/小时、至少2000mg/L/小时、至少2100mg/L/小时、至少2200mg/L/小时、至少2300mg/L/小时、至少2400mg/L/小时或至少2500mg/L/小时。另外,所述生产率可为2500mg/L/小时或更低、2000mg/L/OD600或更低、1500mg/L/OD600或更低、120mg/L/小时或更低、1000mg/L/小时或更低、800mg/L/小时或更低或600mg/L/小时或更低。因此,所述生产率可由以上终点中的任何两者界定。例如,所述生产率可为3至30mg/L/小时、6至20mg/L/小时或15至30mg/L/小时。根据本公开的方法由重组宿主细胞产生的ω-OH脂肪酸和/或ω-OH脂肪酸衍生物的优选生产率选自500mg/L/小时至2500mg/L/小时或700mg/L/小时至2000mg/L/小时。
术语“总的脂肪种类(FAS)”和“总的脂肪酸产品”可在本文中关于如通过如国际专利申请公布WO 2008/119082中所述的GC-FID所评估存在于样品中的ω-OH脂肪酸和脂肪酸的总量互换使用。
如本文所用,术语“葡萄糖利用率”意指每单位时间由培养物使用的葡萄糖的量,报告为克/升/小时(g/L/h)。
术语“来自可再生原料的碳源”当单独或关于给料来源使用时包括产生碳的任何生物材料(包括可再生原料和/或生物质和/或废物),除了油脂化学品(即,来自植物和动物的精制油,如脂肪酸、脂肪酸酯、TAG、羟基脂肪酸等)和石油化学品(即,来源于石油的化学品,如烷烃、烯烃等)。因此,如本文所用的术语“来自可再生原料的碳源”排除了来源于油脂化学品和石油化学品的碳。在一些实施方案中,所述碳源包括糖或碳水化合物(例如,单糖、二糖或多糖)。在一些实施方案中,所述碳源是葡萄糖和/或蔗糖。在其它实施方案中,所述碳源来源于可再生原料,如来自玉米、甘蔗或木质纤维生物质的碳水化合物;或废物,如甘油、烟道气、合成气;或有机材料的革新,如生物质或天然气;或为光合固定的二氧化碳。在其它实施方案中,生物质被处理成碳源,其适用于生物转化。在其它实施方案中,所述生物质无需进一步处理成碳源,但可直接用作碳源。所述生物质的示例性来源为植物物质或植被,如柳枝稷。另一示例性碳源包括代谢废物,如动物物质(例如牛粪)。碳的进一步示例性来源包括藻类和其它海洋植物。另一碳源(包括生物质)包括来自工业、农业、林业和家庭的废物,包括但不限于发酵废物、发酵生物质、甘油(glycerol/glycerine)、青贮饲料、稻草、木材、污水、垃圾、饰带固体废物(maniple solid waste)、纤维素城市废物和剩余食物。
如本文所用,关于如ω-OH脂肪酸和其衍生物的产物的术语“分离”是指与细胞组分、细胞培养基或化学或合成前体分离的产物。由本文所述的方法产生的脂肪酸和其衍生物(例如ω-OH脂肪酸和/或ω-OH脂肪酸衍生物)可相对不混溶于发酵液中以及细胞质中。因此,所述脂肪酸和其衍生物可细胞内或细胞外收集于有机相中。
如本文所用,术语“纯化(purify)”、“纯化的(purified)”或“纯化(purification)”意指分子通过例如分离(isolation/separation)从其环境中去除或分离。“大体上纯化的”分子是至少约60%(例如至少约70%、至少约75%、至少约85%、至少约90%、至少约95%、至少约97%、至少约99%)与其所缔合的其它组分分离。如本文所用,这些术语还指从样品去除污染物。例如,污染物的去除可引起样品中如ω-OH脂肪酸和/或ω-OH脂肪酸衍生物的脂肪酸衍生物的百分比增加。例如,当脂肪酸衍生物在重组宿主细胞中产生时,所述脂肪酸衍生物可通过去除宿主细胞蛋白质或其它宿主细胞材料而纯化。在纯化之后,样品中脂肪酸衍生物的百分比增加。术语“纯化(purify)”、“纯化的(purified)”和“纯化(purification)”是无需绝对纯度的相对术语。因此,举例来说,当脂肪酸衍生物在重组宿主细胞中产生时,纯化的脂肪酸衍生物是大体上与其它细胞组分(例如,核酸、多肽、脂质、碳水化合物或其它烃)分离的脂肪酸衍生物。
由于细胞中的CYP153A-还原酶杂合融合多肽变体表达而引起的ω-羟基化脂肪酸和脂肪酸衍生物产生
在所述催化结构域的饱和文库中鉴定的有益突变(实施例7)是组合文库的基础以进一步改进cyp153A(G307A)-Red450RhF(A796V)融合蛋白。关于命中的选择标准是(1)增加量的ω-羟基脂肪酸(ω-OH FFA效价);和/或(2)增加的脂肪酸至ω-羟基脂肪酸的转化。改进的变体在下表12中示出,特别是显著改进ω-羟基脂肪酸形成的变体。
表12:来自cyp153A(G307A)-Red450RhF(A796V)(SEQ ID NO:38)的催化结构域的组合文库的改进变体的汇总
在所述催化结构域的组合文库中鉴定的有益突变(参看上文实施例8)是下一轮组合文库的基础以进一步改进cyp153A(G307A)-Red450RhF(A796V)融合蛋白(在高表达水准下的cyp153A(G307A)-Red450RhF(A796V)融合蛋白的催化结构域的组合文库)。关于命中的选择标准是(1)增加量的ω-羟基脂肪酸(ω-OH FFA效价);和/或(2)增加的脂肪酸至ω-羟基脂肪酸的转化。改进的变体在下表12中示出,特别是显著改进ω-羟基脂肪酸形成的变体。
表13:来自cyp153A(G307A)-Red450RhF(A796V)的催化结构域的组合文库的在较高表达水准下的改进变体的汇总
在所述还原酶结构域的饱和文库中鉴定的有益突变(实施例7)是组合文库的基础以进一步改进cyp153A(G307A)-Red450RhF(A796V)融合蛋白。选择标准是(1)增加量的ω-羟基脂肪酸(ω-OH FFA效价);和/或(2)增加的脂肪酸至ω-羟基脂肪酸的转化。改进的变体在表14中示出。
表14:来自cyp153A(G307A)-Red450RhF(A796V)的还原酶结构域的组合文库的改进变体
在所述催化结构域和还原酶结构域的组合文库中鉴定的有益突变(参看上文实施例8-10)是组合文库的基础以进一步改进cyp153A(Q12W,R27L,K119R,S140N,S157R,V159M,S233L,A244R,G307A)-Red450RhF(A796V)融合蛋白(cyp153A(Q12W,R27L,K119R,S140N,S157R,V159M,S233L,A244R,G307A)-Red450RhF(A796V)融合蛋白(SEQ ID NO:98)的催化结构域和还原酶结构域的组合文库)。选择标准是(1)增加量的ω-羟基脂肪酸(ω-OH FFA效价);和/或(2)增加的脂肪酸至ω-羟基脂肪酸的转化。改进的变体在表15中示出。
表15:来自cyp153A(Q12W,R27L,K119R,S140N,S157R,V159M,S233L,A244R,G307A)-Red450RhF(A796V)融合蛋白(SEQ ID NO:98)的催化结构域和还原酶结构域的组合文库的改进变体
鉴于表12-15,在多个实施方案中,当催化脂肪酸(衍生物)转化为ω-羟基化脂肪酸或ω-OH脂肪酸衍生物时,如与例如SEQ ID NO:38或SEQ ID NO:98的CYP153A-还原酶杂合融合多肽相比,本公开的CYP153A-还原酶杂合融合多肽变体提供增加量的ω-羟基脂肪酸(ω-OH FFA效价)。因此,在多个实施方案中,如与例如SEQ ID NO:38或SEQ ID NO:98的CYP153A-还原酶杂合融合多肽相比,本公开的CYP153A-还原酶杂合融合多肽变体提供增加的脂肪酸(衍生物)至ω-羟基脂肪酸或ω-OH脂肪酸衍生物的转化。
本公开提供宿主细胞中ω-OH脂肪酸和ω-OH脂肪酸衍生物的产生。ω-OH脂肪酸产生可由于CYP153A-还原酶杂合融合多肽变体的表达而增强。当与模板CYP153A-还原酶杂合融合多肽相比时,例如当与例如SEQ ID NO:6或SEQ ID NO:38的CYP153A-还原酶杂合融合多肽相比时,所述CYP153A-还原酶杂合融合多肽变体以较高效价产生ω-OH脂肪酸衍生物。在多个实施方案中,当与例如SEQ ID NO:42和/或SEQ ID NO:46的CYP153A-还原酶杂合融合多肽相比时,本公开的CYP153A-还原酶杂合融合多肽变体以较高效价产生ω-OH脂肪酸衍生物。在多个实施方案中,当与例如SEQ ID NO:98的CYP153A-还原酶杂合融合多肽相比时,本公开的CYP153A-还原酶杂合融合多肽变体以较高效价产生ω-OH脂肪酸衍生物。所述CYP153A-还原酶杂合融合多肽变体牵涉于用于ω-OH脂肪酸衍生物的产生的生物合成途径中;其可单独或与其它酶组合使用。例如,所述CYP153A-还原酶杂合融合多肽变体可用于经过工程改造的生物合成途径中,其中硫酯酶(即,天然或异源/外源表达)将酰基-ACP或酰基-CoA转化为脂肪酸。所述CYP153A-还原酶杂合融合多肽变体可接着将脂肪酸转化为ω-OH脂肪酸(参看图1)。所述途径中的另外酶可将ω-OH脂肪酸转化为其它双官能脂肪酸衍生物,如α,ω-二酸。
更具体说来,CYP153A-还原酶杂合融合多肽是与SEQ ID NO:6具有至少70%、71%、72%、73%、74%、75%、76%、77%、78%、79%、80%、81%、82%、83%、84%、85%、86%、87%、88%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或100%序列同一性的多肽序列并且充当引入突变的模板序列以便产生具有用于ω-OH脂肪酸和脂肪酸衍生物的产生的改进的酶活性的变体。所述CYP153A-还原酶杂合融合多肽SEQ ID NO:6是在催化结构域中的位置307处具有突变的P450 Cyp153A(G307A)-RedRhF融合蛋白,其中甘氨酸被丙氨酸取代(参看图3)。这种蛋白是自给自足的并且具有催化脂肪酸反应生成ω-OH脂肪酸的ω-羟化酶酶活性。
在本公开的多个实施方案中,由本公开提供的CYP153A-还原酶杂合融合多肽变体是自给自足的并且具有催化脂肪酸(衍生物)反应生成ω-OH脂肪酸(衍生物)的ω-羟化酶酶活性。在本公开的多个实施方案中,由本公开提供的CYP153A-还原酶杂合融合多肽变体具有催化脂肪酸(衍生物)反应生成ω-OH脂肪酸(衍生物)的ω-羟化酶酶活性,其比例如SEQ ID NO:6或SEQ ID NO:38的CYP153A-还原酶杂合融合多肽的ω-羟化酶酶活性高。在本公开的多个实施方案中,由本公开提供的CYP153A-还原酶杂合融合多肽变体具有催化脂肪酸(衍生物)反应生成ω-OH脂肪酸(衍生物)的ω-羟化酶酶活性,其比例如SEQ ID NO:42或SEQ ID NO:46的CYP153A-还原酶杂合融合多肽的ω-羟化酶酶活性高。在本公开的多个实施方案中,由本公开提供的CYP153A-还原酶杂合融合多肽变体具有催化脂肪酸(衍生物)反应生成ω-OH脂肪酸(衍生物)的ω-羟化酶酶活性,其比例如SEQ ID NO:98的CYP153A-还原酶杂合融合多肽的ω-羟化酶酶活性高。
在一个实施方案中,CYP153A-还原酶杂合融合多肽变体是指经过修饰的CYP153A-还原酶杂合融合多肽,其还原酶结构域中具有至少一个另外的突变,包括但不限于在氨基酸位置796、141、231、27、82、178、309、407、415、516和/或666或其组合处的突变。重组宿主细胞中CYP153A-还原酶杂合融合多肽变体的表达引起当与相应宿主细胞中CYP153A-还原酶杂合融合多肽的表达相比时ω-OH脂肪酸和/或ω-OH脂肪酸衍生物或其组合物的改进的效价、产率和/或生产率。
CYP153A-还原酶杂合融合多肽变体的实例为SEQ ID NO:38,其在还原酶结构域中的位置796处具有一个另外的突变,其中丙氨酸被缬氨酸置换(参看图4)。这种CYP153A-还原酶杂合融合多肽变体具有与SEQ ID NO:38具有至少70%、71%、72%、73%、74%、75%、76%、77%、78%、79%、80%、81%、82%、83%、84%、85%、86%、87%、88%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或100%序列同一性的多肽序列并且其进一步充当模板序列以产生另外突变来提供另外变体。CYP153A-还原酶杂合融合多肽变体SEQ ID NO:38是P450 Cyp153A(G307A)-RedRhF(A796V)融合蛋白(参看图5),在催化结构域中具有一个突变(G307A),在还原酶结构域中具有一个突变(A796V),是自给自足的并且具有催化脂肪酸至ω-OH脂肪酸的反应的ω-羟化酶酶活性。在一个实施方案中,所述CYP153A-还原酶杂合融合多肽变体是经过修饰的CYP153A-还原酶杂合融合多肽,其催化结构域和/或还原酶结构域中具有至少一个另外突变,包括但不限于在氨基酸位置9、10、11、12、13、14、27、28、61、77、119、140、141、149、157、159、231、233、244、254、271、309、327、407、413、451、480、527、544、557、567、591、648、649、703、706、719、745、747、749、757、770、771和784或其组合处的突变(参看例如SEQ ID NOS:47-164,其是指所述CYP153A-还原酶杂合融合多肽变体的核酸和蛋白质序列)。在一个实施方案中,重组宿主细胞中CYP153A-还原酶杂合融合多肽变体的表达引起当与相应宿主细胞中CYP153A-还原酶杂合融合多肽变体SEQID NO:38(即,模板变体)的表达相比时ω-OH脂肪酸和/或ω-OH脂肪酸衍生物的改进的效价、产率和/或生产率。在另一实施方案中,重组宿主细胞中CYP153A-还原酶杂合融合多肽变体的表达引起当与CYP153A-还原酶杂合融合多肽SEQ ID NO:6(即,模板多肽)的表达相比时ω-OH脂肪酸和/或ω-OH脂肪酸衍生物的改进的效价、产率和/或生产率。在一个实施方案中,重组宿主细胞中CYP153A-还原酶杂合融合多肽变体的表达引起当与相应宿主细胞中例如SEQ ID NO:42的CYP153A-还原酶杂合融合多肽变体的表达相比时ω-OH脂肪酸和/或ω-OH脂肪酸衍生物的改进的效价、产率和/或生产率。在一个实施方案中,重组宿主细胞中CYP153A-还原酶杂合融合多肽变体的表达引起当与相应宿主细胞中例如SEQ ID NO:46的CYP153A-还原酶杂合融合多肽变体的表达相比时ω-OH脂肪酸和/或ω-OH脂肪酸衍生物的改进的效价、产率和/或生产率。在一个实施方案中,重组宿主细胞中CYP153A-还原酶杂合融合多肽变体的表达引起当与相应宿主细胞中例如SEQ ID NO:98的CYP153A-还原酶杂合融合多肽变体的表达相比时ω-OH脂肪酸和/或ω-OH脂肪酸衍生物的改进的效价、产率和/或生产率。
当细胞已经用CYP153A-还原酶杂合融合多肽变体转化时,其为表达所述CYP153A-还原酶杂合融合多肽变体的细胞(例如,重组细胞)。在一个实施方案中,由表达所述CYP153A-还原酶杂合融合多肽变体的细胞产生的ω-OH脂肪酸的效价和/或产率是表达所述CYP153A-还原酶杂合融合多肽的相应细胞的效价和/或产率的至少两倍。在另一实施方案中,由表达本公开的CYP153A-还原酶杂合融合多肽变体的细胞产生的ω-OH脂肪酸的效价和/或产率是表达CYP153A-还原酶杂合融合多肽模板变体、特别是CYP153A-还原酶杂合融合多肽SEQ ID NO:6或SEQ ID NO:38的相应细胞的效价和/或产率的至少两倍。在另一实施方案中,由表达本公开的CYP153A-还原酶杂合融合多肽变体的细胞产生的ω-OH脂肪酸的效价和/或产率是表达例如SEQ ID NO:42或SEQ ID NO:46的CYP153A-还原酶杂合融合多肽的相应细胞的效价和/或产率的至少两倍。在另一实施方案中,由表达本公开的CYP153A-还原酶杂合融合多肽变体的细胞产生的ω-OH脂肪酸的效价和/或产率是表达例如SEQ IDNO:98的CYP153A-还原酶杂合融合多肽的相应细胞的效价和/或产率的至少两倍。在如大肠杆菌的宿主中,ω-OH脂肪酸可通过天然或异源表达的酶转化为双官能脂肪酸衍生物。在另一实施方案中,由表达所述CYP153A-还原酶杂合融合多肽变体的细胞产生的ω-OH脂肪酸或其衍生物的效价和/或产率比表达所述CYP153A-还原酶杂合融合多肽的相应细胞的效价和/或产率大至少约1倍、至少约2倍、至少约3倍、至少约4倍、至少约5倍、至少约6倍、至少约7倍、至少约8倍、至少约9倍或至少约10倍。在另一实施方案中,由表达本公开的CYP153A-还原酶杂合融合多肽变体的细胞产生的ω-OH脂肪酸或其衍生物的效价和/或产率比表达CYP153A-还原酶杂合融合多肽模板变体、特别是CYP153A-还原酶杂合融合多肽SEQ ID NO:6或SEQ ID NO:38的相应细胞的效价和/或产率大至少约1倍、至少约2倍、至少约3倍、至少约4倍、至少约5倍、至少约6倍、至少约7倍、至少约8倍、至少约9倍或至少约10倍。在另一实施方案中,由表达本公开的CYP153A-还原酶杂合融合多肽变体的细胞产生的ω-OH脂肪酸的效价和/或产率是表达例如SEQ ID NO:42或SEQ ID NO:46的CYP153A-还原酶杂合融合多肽的相应细胞的效价和/或产率的至少两倍。在另一实施方案中,由表达本公开的CYP153A-还原酶杂合融合多肽变体的细胞产生的ω-OH脂肪酸的效价和/或产率是表达例如SEQ IDNO:98的CYP153A-还原酶杂合融合多肽的相应细胞的效价和/或产率的至少两倍。在一个实施方案中,由表达本公开的CYP153A-还原酶杂合融合多肽变体的细胞产生的ω-OH脂肪酸或其衍生物的效价和/或产率比表达模板或参考CYP153A-还原酶杂合融合多肽(例如,表达例如SEQ ID NO:6或SEQ ID NO:38的CYP153A-还原酶杂合融合多肽)的相应细胞的效价和/或产率大至少约1%、至少约2%、至少约3%、至少约4%、至少约5%、至少约6%、至少约7%、至少约8%、至少约9%或至少约10%。在另一实施方案中,由表达本公开的CYP153A-还原酶杂合融合多肽变体的细胞产生的ω-OH脂肪酸或其衍生物的效价和/或产率比表达例如SEQ ID NO:42或SEQ ID NO:46的CYP153A-还原酶杂合融合多肽模板变体的相应细胞的效价和/或产率大至少约1%、至少约2%、至少约3%、至少约4%、至少约5%、至少约6%、至少约7%、至少约8%、至少约9%或至少约10%。在另一实施方案中,由表达本公开的CYP153A-还原酶杂合融合多肽变体的细胞产生的ω-OH脂肪酸或其衍生物的效价和/或产率比表达例如SEQ ID NO:98的CYP153A-还原酶杂合融合多肽模板变体的相应细胞的效价和/或产率大至少约1%、至少约2%、至少约3%、至少约4%、至少约5%、至少约6%、至少约7%、至少约8%、至少约9%或至少约10%。
在另一实施方案中,由于CYP153A-还原酶杂合融合多肽变体的表达在重组细胞中产生的ω-OH脂肪酸或其衍生物的效价和/或产率比表达例如SEQ ID NO:6或SEQ ID NO:38的CYP153A-还原酶杂合融合多肽的相应细胞的效价和/或产率大至少约20%至至少约80%。在另一实施方案中,由于CYP153A-还原酶杂合融合多肽变体的表达在重组细胞中产生的ω-OH脂肪酸或其衍生物的效价和/或产率比表达例如SEQ ID NO:42或SEQ ID NO:46的CYP153A-还原酶杂合融合多肽的相应细胞的效价和/或产率大至少约20%至至少约80%。在另一实施方案中,由于CYP153A-还原酶杂合融合多肽变体的表达在重组细胞中产生的ω-OH脂肪酸或其衍生物的效价和/或产率比表达例如SEQ ID NO:98的CYP153A-还原酶杂合融合多肽的相应细胞的效价和/或产率大至少约20%至至少约80%。
在一些实施方案中,由细胞产生的ω-OH脂肪酸的效价和/或产率比表达所述CYP153A-还原酶杂合融合多肽的相应细胞的效价和/或产率大至少约20%、至少约25%、至少约30%、至少约35%、至少约40%、至少约45%、至少约50%、至少约55%、至少约60%、至少约65%、至少约70%、至少约75%、至少约80%、至少约85%、至少约90%、至少约95%、至少约97%、至少约98%或至少约100%。在其它实施方案中,由细胞或本公开的重组微生物产生的ω-OH脂肪酸的效价和/或产率比表达CYP153A-还原酶杂合融合多肽模板变体、特别是例如SEQ ID NO:6或SEQ ID NO:38的CYP153A-还原酶杂合融合多肽的相应细胞的效价和/或产率大至少约20%、至少约25%、至少约30%、至少约35%、至少约40%、至少约45%、至少约50%、至少约55%、至少约60%、至少约65%、至少约70%、至少约75%、至少约80%、至少约85%、至少约90%、至少约95%、至少约97%、至少约98%或至少约100%。在其它实施方案中,由细胞或本公开的重组微生物产生的ω-OH脂肪酸的效价和/或产率比表达例如SEQ ID NO:42或SEQ ID NO:46的CYP153A-还原酶杂合融合多肽的相应细胞的效价和/或产率大至少约20%、至少约25%、至少约30%、至少约35%、至少约40%、至少约45%、至少约50%、至少约55%、至少约60%、至少约65%、至少约70%、至少约75%、至少约80%、至少约85%、至少约90%、至少约95%、至少约97%、至少约98%或至少约100%。在其它实施方案中,由细胞或本公开的重组微生物产生的ω-OH脂肪酸的效价和/或产率比表达例如SEQ IDNO:98的CYP153A-还原酶杂合融合多肽的相应细胞的效价和/或产率大至少约20%、至少约25%、至少约30%、至少约35%、至少约40%、至少约45%、至少约50%、至少约55%、至少约60%、至少约65%、至少约70%、至少约75%、至少约80%、至少约85%、至少约90%、至少约95%、至少约97%、至少约98%或至少约100%。
因此,本公开提供重组宿主细胞,所述细胞已经工程改造以表达本公开的CYP153A-还原酶杂合融合多肽变体,从而产生ω-OH脂肪酸或其衍生物。所述变体的实例描绘于序列表A、B和C(下述)中。在一个实施方案中,ω-OH脂肪酸的生物合成相对于表达CYP153A-还原酶杂合融合多肽的宿主细胞增强,所述宿主细胞即表达基于例如SEQ ID NO:6、SEQ ID NO:38、SEQ ID NO:42或SEQ ID NO:46的CYP153A-还原酶杂合融合多肽或具有相同酶功能的其它多肽的宿主细胞。在一个实施方案中,ω-OH脂肪酸的生物合成相对于表达CYP153A-还原酶杂合融合多肽的宿主细胞增强,所述宿主细胞即表达基于例如SEQ ID NO:98的CYP153A-还原酶杂合融合多肽的宿主细胞。在另一实施方案中,ω-OH脂肪酸的生物合成相对于表达CYP153A-还原酶杂合融合多肽模板变体的宿主细胞增强,所述宿主细胞即表达基于SEQ ID NO:38的CYP153A-还原酶杂合融合多肽或具有相同酶功能的其它多肽的宿主细胞。在另一实施方案中,ω-OH脂肪酸的生物合成相对于表达CYP153A-还原酶杂合融合多肽模板变体的宿主细胞增强,所述宿主细胞即表达基于SEQ ID NO:6的CYP153A-还原酶杂合融合多肽或具有相同酶功能的其它多肽的宿主细胞。在另一实施方案中,ω-OH脂肪酸的生物合成相对于表达CYP153A-还原酶杂合融合多肽模板变体的宿主细胞增强,所述宿主细胞即表达基于例如SEQ ID NO:42的CYP153A-还原酶杂合融合多肽或具有相同酶功能的其它多肽的宿主细胞。在另一实施方案中,ω-OH脂肪酸的生物合成相对于表达CYP153A-还原酶杂合融合多肽模板变体的宿主细胞增强,所述宿主细胞即表达基于例如SEQ ID NO:46的CYP153A-还原酶杂合融合多肽或具有相同酶功能的其它多肽的宿主细胞。在另一实施方案中,ω-OH脂肪酸的生物合成相对于表达CYP153A-还原酶杂合融合多肽模板变体的宿主细胞增强,所述宿主细胞即表达基于例如SEQ ID NO:98的CYP153A-还原酶杂合融合多肽或具有相同酶功能的其它多肽的宿主细胞。多种不同宿主细胞可经过修饰以表达所述CYP153A-还原酶杂合融合多肽变体,如本文所述的那些,从而产生适用于ω-OH脂肪酸和ω-OH脂肪酸衍生物或其组合物的增强产生的重组宿主细胞。所产生的ω-OH脂肪酸的实例为C6、C7、C8、C9、C10、C11、C12、C13、C14、C15、C16、C17、C18、C19、C20、C8:1、C9:1、C10:1、C11:1、C12:1、C13:1、C14:1、C15:1、C16:1、C17:1、C18:1、C19:1和/或C20:1脂肪酸。在一个实施方案中,所述ω-OH脂肪酸为ω-OH C8:0脂肪酸、ω-OH C10:0脂肪酸、ω-OH C12:0脂肪酸、ω-OH C14:0脂肪酸、ω-OH C16:0脂肪酸、ω-OH C18:0脂肪酸、ω-OH C20:0脂肪酸、ω-OH C8:1脂肪酸、ω-OH C10:1脂肪酸、ω-OH C12:1脂肪酸、ω-OH C14:1脂肪酸、ω-OH C16:1脂肪酸、ω-OH C18:1脂肪酸、ω-OH C20:1脂肪酸等。应了解,多种细胞可提供遗传物质的来源,包括编码适用于如本文所述的重组宿主细胞的多肽的多核苷酸序列。
途径工程改造和酶活性
脂肪酸合成是细菌生物合成机构的最保守系统之一。脂肪酸合酶(FAS)多酶复合物存在于所有细菌和真核生物中。大多数FAS相关基因是细胞生长和存活不可或缺的。真核和细菌FAS基本上驱动相同类型的生物化学转化。在真核生物中,FAS被称作FAS I并且大多数其催化结构域由一条多肽链(不可分离)编码。在如细菌的原核生物中,FAS被称作FASII并且其个别酶和载体蛋白由编码分离(可分离)蛋白质的独立基因编码。因而,FASII是具有显著变化和独特特质的复杂系统。
酰基载体蛋白(ACP)连同FAS途径中的酶控制在原生生物中产生的脂肪酸的长度、饱和和分支的程度。这种途径中的步骤由脂肪酸生物合成(FAB)和乙酰基-CoA羧化酶(ACC)基因家族的酶催化。例如,可包括于FAS途径中的酶包括AccABCD、FabD、FabH、FabG、FabA、FabZ、FabI、FabK、FabL、FabM、FabB和FabF。视所需产物而定,这些基因中的一者或多者可减弱或过表达。因而,原核生物已经工程改造以增加来自如葡萄糖或其它碳源的可再生原料的脂肪酸衍生物的产生。本文中,主要目的是增加调节脂肪酸衍生物的产生的关键控制酶的活性以便将菌株转化至用于脂肪酸衍生物产生的微生物工厂中,所述脂肪酸衍生物包括脂肪酸甲酯(FAME)、脂肪酸乙酯(FAEE)和脂肪醇(FALC)(参看例如美国专利号8,283,143,以引用的方式并入本文)。
本公开鉴定编码具有酶功能的多肽的CYP153A-还原酶杂合融合多核苷酸以便修饰用于如ω-OH脂肪酸和ω-OH脂肪酸衍生物的所需化合物的产生的酶途径。这些多肽在本文中由酶登录号(EC编号)标识,适用于工程改造脂肪酸途径,所述途径引起如ω-OH脂肪酸衍生物(如α,ω-二酸)的ω-OH脂肪酸和其它双官能分子的产生(参看图1)。
在一个实施方案中,图1描绘使用来源于如葡萄糖的可再生原料的碳源以产生ω-OH脂肪酸衍生物的途径。碳水化合物(例如,葡萄糖)通过原生生物被转化为酰基-硫酯,如酰基-ACP(参看图1中的步骤1)。编码具有脂肪酸降解酶活性的多肽的多核苷酸可任选地被减弱,视所需产物而定(参看下文实施例)。所述多肽的非限制性实例为酰基-CoA合成酶(FadD)和酰基-CoA脱氢酶(FadE)。表1提供在代谢途径内的酶活性(下文)的综合列表,包括可根据本领域中已知的方法任选地减弱的多种脂肪酸降解酶(参看例如美国专利号8,283,143,上文)。
例如,FadR(参看下文表1)是牵涉于脂肪酸降解和脂肪酸生物合成途径中的关键调节因素(Cronan等人,Mol.Microbiol.,29(4):937-943(1998))。大肠杆菌酶FadD(参看下文表1)和脂肪酸转运蛋白FadL是脂肪酸摄取系统的组分。FadL介导脂肪酸转运至细菌细胞中,并且FadD介导酰基-CoA酯的形成。当无法获得其它碳源时,外源脂肪酸由细菌吸收并且转化为酰基-CoA酯,所述酯可结合于转录因子FadR并且抑制编码负责脂肪酸转运(FadL)、活化(FadD)和β-氧化(FadA、FadB和FadE)的蛋白质的fad基因的表达。当可获得碳的替代来源时,细菌合成如酰基-ACP的脂肪酸,所述脂肪酸用于磷脂合成,但并非是β-氧化的底物。因此,酰基-CoA和酰基-ACP均为脂肪酸的独立来源,其可产生不同的最终产物(Caviglia等人,J.Biol.Chem.,279(12):1163-1169(2004))。
表1:酶活性
图1示出示例性途径,其中如酰基-ACP的酰基硫酯可转化为作为前体中间物的C12或C16:1脂肪酸(FFA)。在图1的步骤1中,使用硫酯酶将酰基-ACP转化为FFA。在某些实施方案中,编码硫酯酶的基因为tesA、‘tesA、tesB、fatB1、fatB2、fatB3、fatA1或fatA(还参看表1,其示出具有可用于催化这一步骤的硫酯酶的酶活性的多肽,上文)。在步骤2中,使用CYP153A-还原酶杂合融合多肽或其变体由脂肪酸产生ω-OH脂肪酸(ω-OH FFA)。其它双官能分子可在所述途径的下游产生,例如α,ω-二酸或其它ω-OH脂肪酸衍生物,视存在于所述途径中的酶功能性而定。
CYP153A-还原酶杂合融合多肽
ω-羟化酶(或ω-加氧酶)包括某些非血红素二铁加氧酶(例如,来自恶臭假单胞菌GPo1的alkB)和某些血红素类型P450加氧酶(例如,来自水油海杆菌的ω-羟化酶,如cyp153A)。P450是无处不在地分布的酶,其具有高复杂性并且呈现广泛活性领域。其为由转化各种底物并且催化多种化学反应的基因的超家族编码的蛋白质。Cyp153A是使对ω-位置具有高选择性的烃链羟基化的可溶性细菌细胞色素P450的子家族(van Beilen等人(2006)Appl.Environ.Microbiol.72:59-65)。cyp153A家族的成员已经体外显示选择性地使烷烃、脂肪酸或脂肪醇的ω-位置羟基化,例如来自分支杆菌属种HXN-1500的cyp153A6(Funhoff等人(2006)J.Bacteriol.188:5220-5227)、来自海鱼分支杆菌的cyp153A16和来自极单胞菌属种JS666的cyp153A(Scheps等人(2011)Org.Biomol.Chem.9:6727-6733)以及来自水油海杆菌的cyp153A(Honda-Malca等人(2012)Chem.Commun.48:5115-5117)。以下表2A和2B示出具有可用于产生ω-OH脂肪酸和ω-OH脂肪酸衍生物的ω-羟化酶酶活性的酶和氧化还原伴侣(redox partner)的实例。
表2A:ω-羟化酶酶活性的实例(P450)(EC 1.14.15.3)
表2B:针对ω-羟化酶酶活性的氧化还原伴侣的实例(P450)(EC 1.14.15.3)
如同所有细胞色素P450一样,Cyp153Aω-羟化酶需要用于其催化活性的电子,所述电子经由特异性氧化还原蛋白(如铁氧化还原蛋白和铁氧化还原蛋白还原酶)提供。这些为与cyp153A相互作用的分离蛋白。自给自足的杂合(嵌合)cyp153A加氧酶(即,无需用于活性的分离的铁氧化还原蛋白和铁氧化还原蛋白还原酶蛋白的加氧酶)先前已经通过融合来自泊库岛食烷菌SK2的cyp153A(Kubota等人(2005)Biosci.Biotechnol.Biochem.69:2421-2430;Fujita等人(2009)Biosci.Biotechnol.Biochem.73:1825-1830)与来自P450RhF的还原酶结构域而产生,所述结构域包括黄素单核苷酸(FMN)和NADPH-结合位点和[2FeS]铁氧化还原蛋白中心(Hunter等人(2005)FEBS Lett.579:2215-2220)。P450RhF属于I类P450融合PFOR(DeMot和Parret(2003)Trends Microbiol.10:502)。这种杂合cyp153A-RedRhF融合蛋白在体外生物转化中显示使ω-位置中的辛烷羟基化并且还使如环己烷或丁基苯的其它化合物羟基化。其它自给自足的杂合(嵌合)cyp153A加氧酶已经通过融合来自水油海杆菌的cyp153A与来自P450RhF和P450-BM3的还原酶结构域而产生(Scheps等人(2013)Microb.Biotechnol.6:694-707)。天然P450-还原酶融合蛋白的实例显示于以下表2C和2D中。
表2C:自给自足的ω-1、ω-2、ω-3-羟化酶(EC 1.14.14.1)融合蛋白的实例
表2D:自给自足的I类P450-融合PFOR融合蛋白的实例
假定其针对烃链的ω-位置的高选择性,cyp153A家族加氧酶看来是由可再生碳源产生α,ω-双官能脂肪酸衍生物的合适候选物的良好实例。这将允许开发商业上可行的方法来产生这些有价值的化合物。然而,如同其它细胞色素P450一样,cyp153A家族蛋白迄今已经主要应用于使用纯化的酶或粗细胞溶解产物的体外实验或外源添加脂肪酸衍生物或烃的静止细胞生物转化(Kubota等人、Fujita等人、Honda-Malca等人、Scheps等人,上文)。然而,使用杂合融合的体外程序或静止细胞生物转化并未有益于ω-羟基脂肪酸衍生物的大规模和有成本效益的制造。所属领域中公认的知识是多种细胞色素P450以及alkB类型ω-羟化酶不容易在重组微生物中功能性表达,因为所述酶通常无活性并且其化学性质难以阐明。事实上,迄今已经尝试的使用除脂肪酸-衍生物外的可再生碳源的唯一体内工作使用alkBω-羟化酶并且在高细胞密度发酵中仅实现ω-羟基脂肪酸衍生物的低效价(WO2013/024114A2)。
本公开提供能够体内由可再生碳源有效地产生ω-羟基脂肪酸衍生物的CYP153A-还原酶杂合融合蛋白变体。更具体说来,编码CYP153A(G307A)P450催化结构域的杂合融合蛋白(其中丙氨酸(A)在位置307处取代甘氨酸(G))的来自水油海杆菌的基因与编码来自红球菌属种NCIMB9784的P450RhF的c端含FMN和Fe/S还原酶结构域的基因经由连接体多肽融合。所得多肽是具有相应核酸序列(SEQ ID NO:5)的CYP153A-RedRhF杂合融合多肽(SEQ IDNO:6,参看图3)。当这种CYP153A-还原酶杂合融合蛋白在具有如葡萄糖的简单碳源的大肠杆菌细胞中表达时,脂肪酸衍生物有效地转化为ω-羟基脂肪酸衍生物(参看实施例1)。可用于产生相似CYP153A-还原酶杂合融合多肽的合适ω-羟化酶(EC 1.14.15.3)和其氧化还原伴侣的其它实例列于表2A和2B(上文)中。
CYP153A-还原酶杂合融合多肽变体
本公开鉴定当在宿主细胞中表达时当与CYP153A-还原酶杂合融合多肽相比时,特别是当与在宿主细胞中表达的例如SEQ ID NO:6、SEQ ID NO:38、SEQ ID NO:42、SEQ IDNO:46和SEQ ID NO:98中任一者的CYP153A-还原酶杂合融合多肽相比时,并且更具体说来当与在宿主细胞中表达的CYP153A-还原酶杂合融合多肽SEQ ID NO:38相比时,引起ω-羟基化脂肪酸衍生物组合物的较高效价、产率和/或生产率的CYP153A-还原酶杂合融合多肽变体。在多个实施方案中,本公开提供当与在宿主细胞中表达的例如SEQ ID NO:42、SEQ IDNO:46或SEQ ID NO:98的CYP153A-还原酶杂合融合多肽相比时,引起ω-羟基化脂肪酸衍生物组合物的较高效价、产率和/或生产率的CYP153A-还原酶杂合融合多肽变体。在本公开的非限制性实施例(参看实施例1-7,下文)中,所述杂合CYP153A(G307A)-RedRhF融合多肽(上文)用作模板以有效地工程改造CYP153A-还原酶杂合融合多肽变体,从而产生增加量的ω-OH脂肪酸和ω-OH脂肪酸衍生物。例如,所述CYP153A-还原酶杂合融合多肽变体可体内由如葡萄糖的简单碳源将如十二烷酸的化合物转化为12-羟基十二烷酸。任何简单碳源均合适,例如,如来源于可再生原料。已显示经过工程改造的CYP153A-还原酶杂合融合多肽变体(即,经由经过工程改造的CYP153A-RedRhF杂合融合多肽变体说明)当通过使用来自可再生原料的碳源(如葡萄糖)在如大肠杆菌的宿主细胞中与硫酯酶共同表达时可体内将脂肪酸转化为包括ω-OH脂肪酸的具体所需化合物(参看实施例,下文)。通过遵循本公开,其它杂合融合多肽变体可通过连接如编码CYP153A催化结构域的基因的突变基因至编码c端还原酶结构域的突变基因来进行工程改造(参看表2A-2D以及图5,上文)。本文中涵盖变异,例如使两种基因(P5450催化结构域和还原酶结构域)突变或使一种基因(P450催化结构域或还原酶结构域)突变。遵循这些指示,可由其它类型的ω-羟化酶产生相似的融合蛋白变体。
因此,本公开涉及当在宿主细胞中表达时当与CYP153A-还原酶杂合融合多肽相比时,特别是当与在宿主细胞中表达的例如SEQ ID NO:6、SEQ ID NO:38、SEQ ID NO:42、SEQID NO:46和SEQ ID NO:98中任一者的CYP153A-还原酶杂合融合多肽相比时,并且更具体说来当与在宿主细胞中表达的CYP153A-还原酶杂合融合多肽SEQ ID NO:38相比时,引起ω-羟基化脂肪酸衍生物组合物的高效价、产率和/或生产率的CYP153A-还原酶杂合融合多肽变体。在多个实施方案中,本公开涉及当与在宿主细胞中表达的例如SEQ ID NO:42、SEQ IDNO:46或SEQ ID NO:98的CYP153A-还原酶杂合融合多肽相比时,引起ω-羟基化脂肪酸衍生物组合物的高效价、产率和/或生产率的CYP153A-还原酶杂合融合多肽变体。所述CYP153A-还原酶杂合融合多肽变体在CYP153A结构域或还原酶结构域或两者中具有一个或多个突变。在一个实施方案中,本公开提供一种CYP153A-还原酶杂合融合多肽变体,其与SEQ IDNO:6具有至少约90%、91%、92%、93%、94%、95%、96%、97%、98%或99%序列同一性(参看图3)并且在包括位置27、82、141、178、231、309、407、415、516、666和/或796的氨基酸位置处具有一种或多种突变,其中所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-OH脂肪酸。更具体说来,所述CYP153A-还原酶杂合融合多肽变体具有以下突变中的一者或多者,包括R27L,其中精氨酸(R)被赖氨酸(L)取代;位置R82D,其中精氨酸(R)被天冬氨酸(D)取代;位置V141I,其中缬氨酸被异亮氨酸(I)取代;位置V141Q,其中缬氨酸(V)被谷氨酰胺(Q)取代;位置V141G,其中缬氨酸(V)被甘氨酸(G)取代;位置V141M,其中缬氨酸(V)被甲硫氨酸(M)取代;位置V141L,其中缬氨酸(V)被亮氨酸(L)取代;位置V141T,其中缬氨酸(V)被苏氨酸(T)取代;位置R178N,其中精氨酸(R)被天冬酰胺(N)取代;位置A231T,其中丙氨酸(A)被苏氨酸(T)取代;位置N309R,其中天冬酰胺(N)被精氨酸(R)取代;位置N407A,其中天冬酰胺(N)被丙氨酸(A)取代;位置V415R,其中缬氨酸(V)被精氨酸(R)取代;位置T516V,其中苏氨酸(T)被缬氨酸(V)取代;位置P666A,其中脯氨酸(P)被丙氨酸(A)取代;位置P666D,其中脯氨酸(P)被天冬氨酸(D)取代;和位置A796V,其中丙氨酸(A)被缬氨酸(V)取代。CYP153A-还原酶杂合融合多肽变体的实例包括SEQ ID NO:8、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:14、SEQ ID NO:16、SEQ ID NO:18、SEQ ID NO:20、SEQ ID NO:22、SEQ IDNO:24、SEQ ID NO:26、SEQ ID NO:28或SEQ ID NO:30、SEQ ID NO:32、SEQ ID NO:34、SEQID NO:36、SEQ ID NO:38、SEQ ID NO:40、SEQ ID NO:42、SEQ ID NO:44和SEQ ID NO:46。在一个实施方案中,所述CYP153A-还原酶杂合融合多肽变体为杂合cyp153A-RedRhF型融合蛋白变体。在另一实施方案中,如与由CYP153A-还原酶杂合融合多肽在相应宿主细胞中的表达产生的ω-OH脂肪酸或其组合物的效价相比,在重组宿主细胞中的所述CYP153A-还原酶杂合融合多肽变体引起ω-OH脂肪酸衍生物或其组合物的更高效价。在另一实施方案中,所述CYP153A-还原酶杂合融合多肽变体在氨基酸位置141处具有突变,包括V141I和/或V141T。本文中,如与由CYP153A-还原酶杂合融合多肽的表达产生的ω-OH C6、C7、C8、C9、C10、C11、C12、C13、C14、C15、C16、C17、C18、C19、C20、C8:1、C9:1、C10:1、C11:1、C12:1、C13:1、C14:1、C15:1、C16:1、C17:1、C18:1、C19:1和/或C20:1脂肪酸的效价相比,在重组宿主细胞中具有突变V141I或V141T的CYP153A-还原酶杂合融合多肽变体的表达分别引起ω-OH C6、C7、C8、C9、C10、C11、C12、C13、C14、C15、C16、C17、C18、C19、C20、C8:1、C9:1、C10:1、C11:1、C12:1、C13:1、C14:1、C15:1、C16:1、C17:1、C18:1、C19:1和/或C20:1脂肪酸的更高效价。在一个实施方案中,所述CYP153A-还原酶杂合融合多肽变体具有突变V141I和A231T(SEQ ID NO:32)并且当在具有硫酯酶的酶功能的宿主细胞中表达时产生增加量的ω-OH C6、C7、C8、C9、C10、C11、C12、C13、C14、C15、C16、C17、C18、C19、C20、C8:1、C9:1、C10:1、C11:1、C12:1、C13:1、C14:1、C15:1、C16:1、C17:1、C18:1、C19:1和/或C20:1脂肪酸。在另一实施方案中,所述CYP153A-还原酶杂合融合多肽变体具有突变R27L、R82D、V141M、R178N和N407A(SEQID NO:34)并且当在具有硫酯酶的酶功能的宿主细胞中表达时产生增加量的ω-OH C6、C7、C8、C9、C10、C11、C12、C13、C14、C15、C16、C17、C18、C19、C20、C8:1、C9:1、C10:1、C11:1、C12:1、C13:1、C14:1、C15:1、C16:1、C17:1、C18:1、C19:1和/或C20:1脂肪酸。在另一实施方案中,所述CYP153A-还原酶杂合融合多肽变体具有突变P666A(SEQ ID NO:36)并且当在具有硫酯酶的酶功能的宿主细胞中表达时产生增加量的ω-OH C6、C7、C8、C9、C10、C11、C12、C13、C14、C15、C16、C17、C18、C19、C20、C8:1、C9:1、C10:1、C11:1、C12:1、C13:1、C14:1、C15:1、C16:1、C17:1、C18:1、C19:1和/或C20:1脂肪酸。在另一实施方案中,所述CYP153A-还原酶杂合融合多肽变体在其还原酶结构域中具有突变A796V(SEQ IDNO:38)(参看图5)并且当在具有硫酯酶的酶功能的宿主细胞中表达时产生增加量的ω-OHC6、C7、C8、C9、C10、C11、C12、C13、C14、C15、C16、C17、C18、C19、C20、C8:1、C9:1、C10:1、C11:1、C12:1、C13:1、C14:1、C15:1、C16:1、C17:1、C18:1、C19:1和/或C20:1脂肪酸。在另一实施方案中,所述CYP153A-还原酶杂合融合多肽变体在其还原酶结构域中具有突变A796V、P666D和T516V(SEQ ID NO:40)并且当在具有硫酯酶的酶功能的宿主细胞中表达时产生增加量的ω-OH C6、C7、C8、C9、C10、C11、C12、C13、C14、C15、C16、C17、C18、C19、C20、C8:1、C9:1、C10:1、C11:1、C12:1、C13:1、C14:1、C15:1、C16:1、C17:1、C18:1、C19:1和/或C20:1脂肪酸。在另一实施方案中,所述CYP153A-还原酶杂合融合多肽变体在其催化结构域中具有突变V141I和A231T并且在其还原酶结构域中具有突变A796V(SEQ ID NO:42)并且当在具有硫酯酶的酶功能的宿主细胞中表达时产生增加量的ω-OHC6、C7、C8、C9、C10、C11、C12、C13、C14、C15、C16、C17、C18、C19、C20、C8:1、C9:1、C10:1、C11:1、C12:1、C13:1、C14:1、C15:1、C16:1、C17:1、C18:1、C19:1和/或C20:1脂肪酸。在另一实施方案中,所述CYP153A-还原酶杂合融合多肽变体在其催化结构域中具有突变R27L、R82D、V141M、R178N和N407A并且在其还原酶结构域中具有突变A796V(SEQ ID NO:44)并且当在具有硫酯酶的酶功能的宿主细胞中表达时产生增加量的ω-OH C6、C7、C8、C9、C10、C11、C12、C13、C14、C15、C16、C17、C18、C19、C20、C8:1、C9:1、C10:1、C11:1、C12:1、C13:1、C14:1、C15:1、C16:1、C17:1、C18:1、C19:1和/或C20:1脂肪酸。在另一实施方案中,所述CYP153A-还原酶杂合融合多肽变体在其催化结构域中具有突变V141T和A231T并且在其还原酶结构域中具有突变A796V(SEQ ID NO:46)并且当在具有硫酯酶的酶功能的宿主细胞中表达时产生增加量的ω-OH C6、C7、C8、C9、C10、C11、C12、C13、C14、C15、C16、C17、C18、C19、C20、C8:1、C9:1、C10:1、C11:1、C12:1、C13:1、C14:1、C15:1、C16:1、C17:1、C18:1、C19:1和/或C20:1脂肪酸。在一个实施方案中,当与SEQ ID NO:6相比时,SEQ ID NO:32、SEQ ID NO:34、SEQ IDNO:36、SEQ ID NO:38、SEQ ID NO:40、SEQ ID NO:42、SEQ ID NO:44和SEQ ID NO:46的变体产生增加量的ω-OH脂肪酸或脂肪酸衍生物。在一个实施方案中,这些ω-OH脂肪酸为ω-OHC8:0脂肪酸、ω-OH C10:0脂肪酸、ω-OH C12:0脂肪酸、ω-OH C14:0脂肪酸、ω-OH C16:0脂肪酸、ω-OH C18:0脂肪酸、ω-OH C20:0脂肪酸、ω-OH C8:1脂肪酸、ω-OH C10:1脂肪酸、ω-OH C12:1脂肪酸、ω-OH C14:1脂肪酸、ω-OH C16:1脂肪酸、ω-OH C18:1脂肪酸、ω-OH C20:1脂肪酸等。
本公开鉴定CYP153A-还原酶杂合融合相关多核苷酸和多肽变体。所述CYP153A-还原酶杂合多肽变体包括SEQ ID NO:8、10、12、14、16、18、20、22、24、26、28、30、32、34、36、38、40、42、44和46。所述CYP153A-还原酶杂合融合核酸变体(DNA序列)包括SEQ ID NO:7、9、11、13、15、17、19、21、23、25、27、29、31、33、35、37、39、41、43、45和47。然而,应认识到与CYP153A-还原酶杂合融合多核苷酸变体的绝对序列同一性并非必需的。例如,可进行特定多核苷酸序列的改变并且针对活性筛选编码的多肽。所述改变典型地包括保守性突变和沉默突变,例如通过密码子优化。经过修饰或突变的(即,突变型)多核苷酸和编码的变体多肽可使用所属领域中已知的方法针对所需功能进行筛选,所述功能如与野生型或模板多肽相比改进的功能,包括但不限于增加的催化活性、增加的稳定性或降低的抑制作用(例如,降低的反馈抑制作用)。本公开鉴定牵涉于本文中根据酶分类(EC)编号描述的脂肪酸生物合成途径的多个步骤(即,反应)中的酶活性,并且提供由所述EC编号归类的示例性多肽(例如,充当特异性酶并且呈现特异性酶活性)和编码所述多肽的示例性多核苷酸。本文中由序列标识号(SEQ ID NO;上文)标识的所述示例性多肽和多核苷酸适用于工程改造宿主细胞(如图1中所示的细胞)中的脂肪酸途径。然而,应了解本文所述的多肽和多核苷酸为示例性的并且因此非限制性的。本文所述的示例性多肽的同系物的序列可由本领域技术人员使用数据库获得,所述数据库例如由美国国家生物技术信息中心(NCBI)提供的Entrez数据库、由瑞士生物信息研究所提供的ExPasy数据库、由德国不伦瑞克理工大学提供的BRENDA数据库和由京都大学和东京大学生物信息学中心提供的KEGG数据库,其均可可在万维网上获得。
在一个实施方案中,用于实践本公开的CYP153A-还原酶杂合融合多肽变体与SEQID NO:8、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:14、SEQ ID NO:16、SEQ ID NO:18、SEQID NO:20、SEQ ID NO:22、SEQ ID NO:24、SEQ ID NO:26、SEQ ID NO:28或SEQ ID NO:30、SEQ ID NO:32、SEQ ID NO:34、SEQ ID NO:36、SEQ ID NO:38、SEQ ID NO:40、SEQ ID NO:42、SEQ ID NO:44和SEQ ID NO:46具有至少约90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或100%序列同一性。在一些实施方案中,所述CYP153A-还原酶杂合融合多肽变体来源于其中在催化结构域中丙氨酸(A)被甘氨酸(G)取代的来自水油海杆菌的CYP153A(G307A)多肽,并且与来自红球菌属种NCIMB9784的P450RhF的还原酶结构域通过连接体多肽融合。细胞色素P450RhF是自给自足的,呈现高底物混杂程度并且催化广泛范围的官能团。在其它实施方案中,用于实践本公开的CYP153A-还原酶杂合融合多肽变体与SEQID NO:6、SEQ ID NO:8、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:14、SEQ ID NO:16、SEQID NO:18、SEQ ID NO:20、SEQ ID NO:22、SEQ ID NO:24、SEQ ID NO:26、SEQ ID NO:28或SEQ ID NO:30、SEQ ID NO:32、SEQ ID NO:34、SEQ ID NO:36、SEQ ID NO:38、SEQ ID NO:40、SEQ ID NO:42、SEQ ID NO:44或SEQ ID NO:46具有至少约75%、76%、77%、78%、79%、80%、81%、82%、83%、84%、85%、86%、87%、88%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%或至少99%序列同一性,并且还包括一种或多种取代,所述取代产生如本文所述的适用特征和/或特性。在其它实施方案中,用于实践本公开的CYP153A-还原酶杂合融合多肽变体与SEQ ID NO:8、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:14、SEQ IDNO:16、SEQ ID NO:18、SEQ ID NO:20、SEQ ID NO:22、SEQ ID NO:24、SEQ ID NO:26、SEQ IDNO:28或SEQ ID NO:30、SEQ ID NO:32、SEQ ID NO:34、SEQ ID NO:36、SEQ ID NO:38、SEQID NO:40、SEQ ID NO:42、SEQ ID NO:44或SEQ ID NO:46具有至少约100%、99%、98%、97%、96%、95%、94%、93%、92%、91%或90%序列同一性。在其它实施方案中,所述CYP153A-还原酶杂合融合多肽变体的P450催化结构域来源于除水油海杆菌外的生物。所述其它生物包括但不限于不动杆菌属种、海分支杆菌、极单胞菌属种、泊库岛食烷菌、伯克氏菌、新月柄杆菌、海王生丝单胞菌、沼泽红假单胞菌、鞘氨醇单胞菌属种、分支杆菌属种。在其它实施方案中,所述CYP153A-还原酶杂合融合多肽变体的还原酶结构域来源于除红球菌属种外的生物。所述其它生物包括但不限于马红球菌、抗辐射不动杆菌、鼻疽伯克氏菌、鼻疽伯克氏菌、富养罗氏菌、耐重金属贪铜菌。
在一个相关实施方案中,本公开包括CYP153A-还原酶杂合融合多核苷酸变体,其与SEQ ID NO:5、SEQ ID NO:7、SEQ ID NO:9、SEQ ID NO:11、SEQ ID NO:13、SEQ ID NO:15、SEQ ID NO:17、SEQ ID NO:19、SEQ ID NO:21、SEQ ID NO:23、SEQ ID NO:25、SEQ ID NO:27、SEQ ID NO:29、SEQ ID NO:31、SEQ ID NO:33、SEQ ID NO:35、SEQ ID NO:37、SEQ IDNO:39、SEQ ID NO:41、SEQ ID NO:43、SEQ ID NO:45或SEQ ID NO:47具有至少约75%、76%、77%、78%、79%、80%、81%、82%、83%、84%、85%、86%、87%、88%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%或至少99%序列同一性。在一些实施方案中,所述核酸序列编码具有一种或多种取代的CYP153A-还原酶杂合融合多肽变体,所述取代产生如本文所述的改进的特征和/或特性。在另一相关实施方案中,用于实践本公开的CYP153A-还原酶杂合融合多肽变体由与SEQ ID NO:7、SEQ ID NO:9、SEQ ID NO:11、SEQ IDNO:13、SEQ ID NO:15、SEQ ID NO:17、SEQ ID NO:19、SEQ ID NO:21、SEQ ID NO:23、SEQ IDNO:25、SEQ ID NO:27、SEQ ID NO:29、SEQ ID NO:31、SEQ ID NO:33、SEQ ID NO:35、SEQ IDNO:37、SEQ ID NO:39、SEQ ID NO:41、SEQ ID NO:43、SEQ ID NO:45或SEQ ID NO:47具有至少约100%、99%、98%、97%、96%、95%、94%、93%、92%、91%或90%序列同一性的核苷酸序列编码。另一方面,本公开涉及CYP153A-还原酶杂合融合多肽变体,所述变体涵盖由核酸序列编码的氨基酸序列,所述核酸序列在严格条件下在对应于SEQ ID NO:7、SEQ ID NO:9、SEQ ID NO:11、SEQ ID NO:13、SEQ ID NO:15、SEQ ID NO:17、SEQ ID NO:19、SEQ ID NO:21、SEQ ID NO:23、SEQ ID NO:25、SEQ ID NO:27、SEQ ID NO:29、SEQ ID NO:31、SEQ IDNO:33、SEQ ID NO:35、SEQ ID NO:37、SEQ ID NO:39、SEQ ID NO:41、SEQ ID NO:43、SEQ IDNO:45或SEQ ID NO:47的核酸序列的基本上完整长度内杂交。在一些实施方案中,所述CYP153A-还原酶杂合融合多肽变体来源于水油海杆菌。在其它实施方案中,所述P450杂合融合多肽来源于不动杆菌属种、海分支杆菌、极单胞菌属种、泊库岛食烷菌、伯克氏菌、新月柄杆菌、海王生丝单胞菌、沼泽红假单胞菌、鞘氨醇单胞菌属种和分支杆菌属种。
另外的CYP153A-还原酶杂合融合多肽变体
本公开鉴定另外的CYP153A-还原酶杂合融合相关多核苷酸和多肽变体,其中变体用作模板(模板变体)。所述CYP153A-还原酶杂合融合多肽模板变体(SEQ ID NO:38)是基于P540CYP153A(G307A)-Red450RhF(A796V)融合多肽并且包括在催化结构域中的突变G307A(其中甘氨酸(G)被丙氨酸(A)置换)和在还原酶结构域中的突变A796V(其中丙氨酸(A)被缬氨酸(V)置换),其中连接体多肽连接所述催化结构域至所述还原酶结构域(参看图4和5)。在一些实施方案中,来自水油海杆菌的CYP153A多肽与来自红球菌属种NCIMB9784的P450RhF的还原酶结构域经由连接体融合。如上文所注明,细胞色素P450RhF是自给自足的,呈现高底物混杂程度并且催化广泛范围的官能团。在催化结构域中的突变G307A和在还原酶结构域中的突变A796V是改进cyp153A的ω-羟化酶活性的有益突变(参看SEQ ID NO:38)。建立cyp153A-Red450RhF融合蛋白的全饱和文库并且针对显示与P540 cyp153A(G307A)-Red450RhF(A796V)(SEQ ID NO:38)相比的改进的变体进行筛选(参看实施例7)。所得CYP153A-还原酶杂合融合多肽变体在实施例(下文)以及序列表B和C中示出。这些CYP153A-还原酶杂合融合多肽变体当与SEQ ID NO:38相比时产生增加量的ω-羟基脂肪酸(ω-OH FFA效价)并且包括SEQ ID NO:48、50、52、54、56、58、60、62、64、66、68、70、72、74、76、78、80、82、84、86、88、90、92、94、96、98、100、102、104、106、108、110、112、114、116、118、120、122、124、126、128、130、132、134、136、138、140、142和144。同样,这些CYP153A-还原酶杂合融合多肽变体当与SEQ ID NO:6相比时产生增加量的ω-羟基脂肪酸(ω-OH FFA效价)并且包括SEQ ID NO:48、50、52、54、56、58、60、62、64、66、68、70、72、74、76、78、80、82、84、86、88、90、92、94、96、98、100、102、104、106、108、110、112、114、116、118、120、122、124、126、128、130、132、134、136、138、140、142、144、146、148、150、152、154、156、158、160、162和164。这些CYP153A-还原酶杂合融合多肽变体可产生增加量的ω-OH脂肪酸,包括C6、C7、C8、C9、C10、C11、C12、C13、C14、C15、C16、C17、C18、C19、C20、C8:1、C9:1、C10:1、C11:1、C12:1、C13:1、C14:1、C15:1、C16:1、C17:1、C18:1、C19:1和/或C20:1脂肪酸和/或脂肪酸衍生物。
在催化结构域中的突变Q12W、R27L、K119R、S140N、S157R、V159M、S233L和A244R(除了突变G307A以外)和在还原酶结构域中的突变A796V是进一步改进cyp153A的ω-羟化酶活性的有益突变(参看SEQ ID NO:98和实施例8)。建立cyp153A-Red450RhF融合蛋白的全饱和文库并且针对显示与SEQ ID NO:98相比的改进的变体进行筛选(参看实施例11)。所得CYP153A-还原酶杂合融合多肽变体在实施例(下文)以及序列表C(下文)中示出。这些CYP153A-还原酶杂合融合多肽变体当与SEQ ID NO:98相比时产生增加量的ω-羟基脂肪酸(ω-OH FFA效价)并且包括SEQ ID NO:146、148、150、152、154、156、158、160、162和164。同样,这些CYP153A-还原酶杂合融合多肽变体当与SEQ ID NO:6以及SEQ ID NO:38相比时产生增加量的ω-羟基脂肪酸(ω-OH FFA效价)并且包括SEQ ID NO:146、148、150、152、154、156、158、160、162和164。这些CYP153A-还原酶杂合融合多肽变体可产生增加量的ω-OH脂肪酸,包括C6、C7、C8、C9、C10、C11、C12、C13、C14、C15、C16、C17、C18、C19、C20、C8:1、C9:1、C10:1、C11:1、C12:1、C13:1、C14:1、C15:1、C16:1、C17:1、C18:1、C19:1和/或C20:1脂肪酸和/或脂肪酸衍生物。
所述CYP153A-还原酶杂合融合核酸变体(DNA序列)包括SEQ ID NO:47、49、51、53、55、57、59、61、63、65、67、69、71、73、75、77、79、81、83、85、87、89、91、93、95、97、99、101、103、105、107、109、111、113、115、117、119、121、123、125、127、129、131、133、135、137、139、141、143、145、147、149、151、153、155、157、159、161和163。然而,应认识到与CYP153A-还原酶杂合融合多核苷酸变体的绝对序列同一性并非必需的。例如,可进行特定多核苷酸序列的改变并且针对活性筛选编码的多肽。所述改变典型地包括保守性突变和沉默突变,例如通过密码子优化。经过修饰或突变的(即,突变型)多核苷酸和编码的变体多肽可使用所属领域中已知的方法针对所需功能进行筛选,所述功能如与野生型或模板多肽相比改进的功能,包括但不限于增加的催化活性、增加的稳定性或降低的抑制作用(例如,降低的反馈抑制作用)。本公开鉴定牵涉于本文中根据酶分类(EC)编号描述的脂肪酸生物合成途径的多个步骤(即,反应)中的酶活性,并且提供由所述EC编号归类的示例性多肽(例如,其充当特异性酶并且呈现特异性酶活性)和编码所述多肽的示例性多核苷酸。本文中由序列标识号(SEQID NO;上文)标识的所述示例性多肽和多核苷酸适用于工程改造宿主细胞(如图1中所示的细胞)中的脂肪酸途径。然而,应了解本文所述的多肽和多核苷酸为示例性的并且因此非限制性的。本文所述的示例性多肽的同系物的序列可由本领域技术人员使用数据库获得,所述数据库例如由美国国家生物技术信息中心(NCBI)提供的Entrez数据库、由瑞士生物信息研究所提供的ExPasy数据库、由德国不伦瑞克理工大学提供的BRENDA数据库和由京都大学和东京大学生物信息学中心提供的KEGG数据库,其均可在万维网上获得。
在多个实施方案中,本公开的CYP153A-还原酶杂合融合多肽变体与氨基酸序列SEQ ID NO:98、SEQ ID NO:100、SEQ ID NO:102、SEQ ID NO:104、SEQ ID NO:106、SEQ IDNO:108、SEQ ID NO:110、SEQ ID NO:112、SEQ ID NO:114、SEQ ID NO:116、SEQ ID NO:118、SEQ ID NO:120、SEQ ID NO:122、SEQ ID NO:124、SEQ ID NO:126、SEQ ID NO:128、SEQ IDNO:130、SEQ ID NO:132、SEQ ID NO:134、SEQ ID NO:136、SEQ ID NO:138、SEQ ID NO:140、SEQ ID NO:142、SEQ ID NO:144、SEQ ID NO:146、SEQ ID NO:148、SEQ ID NO:150、SEQ IDNO:152、SEQ ID NO:154、SEQ ID NO:156、SEQ ID NO:158、SEQ ID NO:160、SEQ ID NO:162和SEQ ID NO:164中的任一者具有至少约80%、81%、82%、83%、84%、85%、86%、87%、88%或89%序列同一性,其中所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-羟基化脂肪酸。优选地,如与通过CYP153A-还原酶杂合融合多肽SEQ ID NO:6或SEQ IDNO:38在相应宿主细胞中的表达产生的ω-羟基化脂肪酸的效价相比,所述CYP153A-还原酶杂合融合多肽变体在重组宿主细胞中表达时提供ω-羟基化脂肪酸的较高效价。在多个实施方案中,本公开的CYP153A-还原酶杂合融合多肽变体与氨基酸序列SEQ ID NO:98、SEQID NO:100、SEQ ID NO:102、SEQ ID NO:104、SEQ ID NO:106、SEQ ID NO:108、SEQ ID NO:110、SEQ ID NO:112、SEQ ID NO:114、SEQ ID NO:116、SEQ ID NO:118、SEQ ID NO:120、SEQID NO:122、SEQ ID NO:124、SEQ ID NO:126、SEQ ID NO:128、SEQ ID NO:130、SEQ ID NO:132、SEQ ID NO:134、SEQ ID NO:136、SEQ ID NO:138、SEQ ID NO:140、SEQ ID NO:142、SEQID NO:144、SEQ ID NO:146、SEQ ID NO:148、SEQ ID NO:150、SEQ ID NO:152、SEQ ID NO:154、SEQ ID NO:156、SEQ ID NO:158、SEQ ID NO:160、SEQ ID NO:162和SEQ ID NO:164中的任一者具有至少约90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或100%序列同一性,其中所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-羟基化脂肪酸。优选地,如与通过CYP153A-还原酶杂合融合多肽SEQ ID NO:6或SEQ ID NO:38在相应宿主细胞中的表达产生的ω-羟基化脂肪酸的效价相比,所述CYP153A-还原酶杂合融合多肽变体在重组宿主细胞中表达时提供ω-羟基化脂肪酸的较高效价。在一些实施方案中,所述CYP153A-还原酶杂合融合多肽变体来源于其中甘氨酸(G)被丙氨酸(A)置换的来自水油海杆菌的CYP153A(G307A)多肽,并且与来自红球菌属种NCIMB9784的P450RhF的还原酶结构域融合,并且包括另外的突变A796V,其中丙氨酸(A)被缬氨酸(V)置换。在其它实施方案中,用于实践本公开的CYP153A-还原酶杂合融合多肽变体与SEQ ID NO:38、SEQ ID NO:48、SEQID NO:50、SEQ ID NO:52、SEQ ID NO:54、SEQ ID NO:56、SEQ ID NO:58、SEQ ID NO:60、SEQID NO:62、SEQ ID NO:64、SEQ ID NO:66、SEQ ID NO:68或SEQ ID NO:70、SEQ ID NO:72、SEQ ID NO:74、SEQ ID NO:76、SEQ ID NO:78、SEQ ID NO:80、SEQ ID NO:82、SEQ ID NO:84、SEQ ID NO:86、SEQ ID NO:88、SEQ ID NO:90、SEQ ID NO:92、SEQ ID NO:94、SEQ IDNO:96、SEQ ID NO:98、SEQ ID NO:100、SEQ ID NO:102、SEQ ID NO:104、SEQ ID NO:106、SEQ ID NO:108、SEQ ID NO:110、SEQ ID NO:112、SEQ ID NO:114、SEQ ID NO:116、SEQ IDNO:118、SEQ ID NO:120、SEQ ID NO:122、SEQ ID NO:124、SEQ ID NO:126、SEQ ID NO:128、SEQ ID NO:130、SEQ ID NO:132、SEQ ID NO:134、SEQ ID NO:136、SEQ ID NO:138、SEQ IDNO:140、SEQ ID NO:142、SEQ ID NO:144、SEQ ID NO:146、SEQ ID NO:148、SEQ ID NO:150、SEQ ID NO:152、SEQ ID NO:154、SEQ ID NO:156、SEQ ID NO:158、SEQ ID NO:160、SEQ IDNO:162和SEQ ID NO:164具有至少约75%、76%、77%、78%、79%、80%、81%、82%、83%、84%、85%、86%、87%、88%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%或至少99%序列同一性,并且还包括一种或多种取代,所述取代产生如本文所述的适用特征和/或特性。在其它实施方案中,用于实践本公开的CYP153A-还原酶杂合融合多肽变体与SEQ ID NO:38、SEQ ID NO:48、SEQ ID NO:50、SEQ ID NO:52、SEQ ID NO:54、SEQ ID NO:56、SEQ ID NO:58、SEQ ID NO:60、SEQ ID NO:62、SEQ ID NO:64、SEQ ID NO:66、SEQ IDNO:68或SEQ ID NO:70、SEQ ID NO:72、SEQ ID NO:74、SEQ ID NO:76、SEQ ID NO:78、SEQID NO:80、SEQ ID NO:82、SEQ ID NO:84、SEQ ID NO:86、SEQ ID NO:88、SEQ ID NO:90、SEQID NO:92、SEQ ID NO:94或SEQ ID NO:96具有至少约100%、99%、98%、97%、96%、95%、94%、93%、92%、91%或90%序列同一性。在其它实施方案中,所述CYP153A-还原酶杂合融合多肽变体的P450催化结构域来源于除水油海杆菌外的生物。所述其它生物包括但不限于不动杆菌属种、海分支杆菌、极单胞菌属种、泊库岛食烷菌、伯克氏菌、新月柄杆菌、海王生丝单胞菌、沼泽红假单胞菌、鞘氨醇单胞菌属种、分支杆菌属种。在其它实施方案中,所述CYP153A-还原酶杂合融合多肽变体的还原酶结构域来源于除红球菌属种外的生物。所述其它生物包括但不限于马红球菌、抗辐射不动杆菌、鼻疽伯克氏菌、鼻疽伯克氏菌、富养罗氏菌、耐重金属贪铜菌。
在一个相关实施方案中,本公开包括CYP153A-还原酶杂合融合多核苷酸变体,其与核酸序列SEQ ID NO:97、SEQ ID NO:99、SEQ ID NO:101、SEQ ID NO:103、SEQ ID NO:105、SEQ ID NO:107、SEQ ID NO:109、SEQ ID NO:111、SEQ ID NO:113、SEQ ID NO:115、SEQID NO:117、SEQ ID NO:119、SEQ ID NO:121、SEQ ID NO:123、SEQ ID NO:125、SEQ ID NO:127、SEQ ID NO:129、SEQ ID NO:131、SEQ ID NO:133、SEQ ID NO:135、SEQ ID NO:137、SEQID NO:139、SEQ ID NO:141、SEQ ID NO:143、SEQ ID NO:145、SEQ ID NO:147、SEQ ID NO:149、SEQ ID NO:151、SEQ ID NO:153、SEQ ID NO:155、SEQ ID NO:157、SEQ ID NO:159、SEQID NO:161和SEQ ID NO:163中的任一者具有至少约75%、76%、77%、78%、79%、80%、81%、82%、83%、84%、85%、86%、87%、88%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%或至少99%序列同一性,其中由所述CYP153A-还原酶杂合融合多核苷酸变体编码的CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-羟基化脂肪酸。优选地,如与通过CYP153A-还原酶杂合融合多肽SEQ ID NO:6或SEQ ID NO:38在相应宿主细胞中的表达产生的ω-羟基化脂肪酸的效价相比,由所述CYP153A-还原酶杂合融合多核苷酸变体编码的所述CYP153A-还原酶杂合融合多肽变体在重组宿主细胞中表达时提供ω-羟基化脂肪酸的较高效价。在一些实施方案中,所述核酸序列编码具有一种或多种取代的CYP153A-还原酶杂合融合多肽变体,所述取代产生如本文所述的改进的特征和/或特性。在另一相关实施方案中,本公开的CYP153A-还原酶杂合融合多肽变体由与核苷酸序列SEQ ID NO:97、SEQ ID NO:99、SEQ ID NO:101、SEQ ID NO:103、SEQ ID NO:105、SEQ ID NO:107、SEQ IDNO:109、SEQ ID NO:111、SEQ ID NO:113、SEQ ID NO:115、SEQ ID NO:117、SEQ ID NO:119、SEQ ID NO:121、SEQ ID NO:123、SEQ ID NO:125、SEQ ID NO:127、SEQ ID NO:129、SEQ IDNO:131、SEQ ID NO:133、SEQ ID NO:135、SEQ ID NO:137、SEQ ID NO:139、SEQ ID NO:141、SEQ ID NO:143、SEQ ID NO:145、SEQ ID NO:147、SEQ ID NO:149、SEQ ID NO:151、SEQ IDNO:153、SEQ ID NO:155、SEQ ID NO:157、SEQ ID NO:159、SEQ ID NO:161和SEQ ID NO:163中的任一者具有至少约100%、99%、98%、97%、96%、95%、94%、93%、92%、91%或90%序列同一性的核苷酸序列编码。另一方面,本公开涉及CYP153A-还原酶杂合融合多肽变体,所述变体涵盖由核酸序列编码的氨基酸序列,所述核酸序列在严格条件下在对应于SEQ IDNO:97、SEQ ID NO:99、SEQ ID NO:101、SEQ ID NO:103、SEQ ID NO:105、SEQ ID NO:107、SEQ ID NO:109、SEQ ID NO:111、SEQ ID NO:113、SEQ ID NO:115、SEQ ID NO:117、SEQ IDNO:119、SEQ ID NO:121、SEQ ID NO:123、SEQ ID NO:125、SEQ ID NO:127、SEQ ID NO:129、SEQ ID NO:131、SEQ ID NO:133、SEQ ID NO:135、SEQ ID NO:137、SEQ ID NO:139、SEQ IDNO:141、SEQ ID NO:143、SEQ ID NO:145、SEQ ID NO:147、SEQ ID NO:149、SEQ ID NO:151、SEQ ID NO:153、SEQ ID NO:155、SEQ ID NO:157、SEQ ID NO:159、SEQ ID NO:161和SEQ IDNO:163中的任一者的核酸序列的基本上完整长度内杂交。在一些实施方案中,所述CYP153A-还原酶杂合融合多肽变体来源于水油海杆菌物种。在其它实施方案中,所述P450杂合融合多肽来源于不动杆菌属种、海分支杆菌、极单胞菌属种、泊库岛食烷菌、伯克氏菌、新月柄杆菌、海王生丝单胞菌、沼泽红假单胞菌、鞘氨醇单胞菌属种和分支杆菌属种。
序列
下文序列表A中所示的变体基于杂合细胞色素P450cyp153A16(G307A)-RedRhF融合蛋白。
下文序列表B中所示的变体基于杂合细胞色素P450cyp153A(G307A)-Red450RhF(A796V)融合蛋白。
下文序列表C中所示的变体基于杂合细胞色素P450cyp153A(Q12W,R27L,K119R,S140N,S157R,V159M,S233L,A244R,G307A)-Red450RhF(A796V)融合蛋白(SEQ ID NO:98)。
*模板SEQ ID NO:98中的一些突变回复变异为野生型。所有变体均含有G307A和A796V突变(SEQ ID NO:38)和另外突变。
下文序列表D中所示的变体基于杂合细胞色素P450cyp153A(Q12W,R27L,K119R,S140N,S157R,V159M,S233L,A244R,G307A)-Red450RhF(A796V)融合蛋白(SEQ ID NO:98)。在这个表中,所有变体均用突变的完整列表(包括模板突变)描绘。
*模板SEQ ID NO:98中的一些突变回复变异为野生型。所有变体均含有G307A和A796V突变(SEQ ID NO:38)和另外突变。
变异和突变
如本文所用的变体多肽是指具有与野生型CYP153A或模板CYP153A-还原酶杂合融合多肽的不同之处在于至少一个氨基酸的氨基酸序列的多肽。例如,所述变体(例如突变体)可具有以下保守氨基酸取代中的一者或多者,包括但不限于如丙氨酸、缬氨酸、亮氨酸和异亮氨酸的脂肪族氨基酸被另一脂肪族氨基酸置换;丝氨酸被苏氨酸置换;苏氨酸被丝氨酸置换;如天冬氨酸和谷氨酸的酸性残基被另一酸性残基置换;如天冬酰胺和谷氨酰胺的具有酰胺基团的残基被另一具有酰胺基团的残基置换;如赖氨酸和精氨酸的碱性残基用另一碱性残基交换;和如苯丙氨酸和酪氨酸的芳香族残基被另一芳香族残基置换。在一些实施方案中,所述变体多肽具有约1、2、3、4、5、6、7、8、9、10、15、20、30、40、50、60、70、80、90、99个或更多个氨基酸取代、添加、插入或缺失。本公开涵盖本公开的CYP153A-还原酶杂合融合多肽变体的片段,其中所述片段催化脂肪酸转化为ω-羟基化脂肪酸,如相应的全长CYP153A-还原酶杂合融合多肽变体。优选地,如与通过例如SEQ ID NO:6或SEQ ID NO:38的模板CYP153A-还原酶杂合融合多肽在相应宿主细胞中的表达产生的ω-羟基化脂肪酸的效价相比,本公开的所述片段在重组宿主细胞中表达时提供ω-羟基化脂肪酸的较高效价。因此,本公开的CYP153A-还原酶杂合融合多肽变体或突变体的片段保留本公开的相应的全长CYP153A-还原酶杂合融合多肽变体或突变体的一些或全部生物功能(例如酶活性,具体说来ω-羟化酶酶活性)。另外,由本公开提供的CYP153A-还原酶杂合融合多肽变体片段保留相应野生型CYP153A多肽或相应的模板CYP153A-还原酶杂合融合多肽(例如,CYP153A-还原酶杂合融合多肽SEQ ID NO:6或SEQ ID NO:38)的一些或全部生物功能(例如酶活性,具体说来ω-羟化酶酶活性)。在一些实施方案中,所述片段保留相应野生型CYP153A多肽或本公开的相应全长CYP153A-还原酶杂合融合多肽变体或相应的模板CYP153A-还原酶杂合融合多肽的至少75%、至少80%、至少90%、至少95%或至少98%或更多生物功能。在其它实施方案中,所述片段或突变体保留相应野生型CYP153A多肽或本公开的相应全长CYP153A-还原酶杂合融合多肽变体或相应的模板CYP153A-还原酶杂合融合多肽的约100%生物功能。在其它实施方案中,一些片段展现如与相应野生型CYP153A多肽或相应的模板CYP153A-还原酶杂合融合多肽相比增加的生物功能。关于确定哪种氨基酸残基可被取代、插入或缺失而不影响生物活性的指导可使用本领域中众所周知的计算机程序,例如LASERGENE软件(DNASTAR,Inc.,Madison,WI)找到。在一些实施方案中,片段展现如与相应野生型CYP153A多肽或相应的或相应的模板CYP153A-还原酶杂合融合多肽相比增加的生物功能。例如,片段可呈现如与相应野生型CYP153A多肽或相应的模板CYP153A-还原酶杂合融合多肽相比酶活性的至少10%、至少25%、至少50%、至少75%或至少90%改进。在其它实施方案中,所述片段呈现如与相应野生型CYP153A多肽或相应的模板CYP153A-还原酶杂合融合多肽相比酶活性的至少100%、至少200%或至少500%改进。根据如下事实,即本公开涵盖如上文所提及的本公开的CYP153A-还原酶杂合融合多肽变体的片段,应理解本文中关于本公开的CYP153A-还原酶杂合融合多肽变体所述的所有结构和功能技术特性还适用于本公开的CYP153A-还原酶杂合融合多肽变体的片段,即使本文中在其中描述本公开的CYP153A-还原酶杂合融合多肽变体的所有结构和功能技术特性的各位置处可未明确地提及所述片段。
应了解本文所述的多肽可具有对多肽功能不具有实质影响的另外保守或非必需氨基酸取代。特定取代是否将被容许(即,将不会不利地影响所需生物功能,如ω-羟化酶酶活性)可如本领域中已知来确定(参看Bowie等人(1990)Science,247:1306-1310)。保守氨基酸取代是其中氨基酸残基被具有类似侧链的氨基酸残基置换的取代。具有类似侧链的氨基酸残基的家族已经在本领域中定义。这些家族包括具有碱性侧链的氨基酸(例如,赖氨酸、精氨酸、组氨酸)、具有酸性侧链的氨基酸(例如,天冬氨酸、谷氨酸)、具有不带电荷的极性侧链的氨基酸(例如,甘氨酸、天冬酰胺、谷氨酰胺、丝氨酸、苏氨酸、酪氨酸、半胱氨酸)、具有非极性侧链的氨基酸(例如,丙氨酸、缬氨酸、亮氨酸、异亮氨酸、脯氨酸、苯丙氨酸、甲硫氨酸、色氨酸)、具有β-分支侧链的氨基酸(例如,苏氨酸、缬氨酸、异亮氨酸)和具有芳香族侧链的氨基酸(例如,酪氨酸、苯丙氨酸、色氨酸、组氨酸)。
变体可天然存在或体外产生。特别地,所述变体可使用基因工程改造技术,如定点诱变、随机化学诱变、核酸外切酶III缺失程序或标准克隆技术来产生。或者,所述变体、突变体、片段、类似物或衍生物可使用化学合成或修饰程序来产生。本领域中众所周知准备变体的方法。例如,变体可通过使用随机和定点诱变来制备。随机和定点诱变是不领域中一般已知的(参看例如Arnold(1993)Curr.Opin.Biotech.4:450-455)。随机诱变可使用易错PCR(参看例如Leung等人(1989)Technique 1:11-15;和Caldwell等人(1992)PCR MethodsApplic.2:28-33)来实现。在易错PCR中,实际PCR在其中DNA聚合酶的拷贝保真度较低,使得沿PCR产物的整个长度获得高点突变率的条件下执行。简单来说,在所述程序中,待诱变的核酸(例如,编码P450蛋白或P450杂合融合多肽的多核苷酸序列)与PCR引物、反应缓冲液、MgCl2、MnCl2、Taq聚合酶和适当浓度的dNTP混合以实现沿PCR产物的整个长度的高点突变率。例如,所述反应可使用20飞摩尔的待诱变的核酸、30皮摩尔的各PCR引物、包含50mMKCl、10mM Tris HCl(pH 8.3)、0.01%明胶的反应缓冲液、7mM MgCl2、0.5mM MnCl2、5单位Taq聚合酶、0.2mM dGTP、0.2mM dATP、1mM dCTP和1mM dTTP执行。PCR可执行30个循环:94℃持续1min,45℃持续1min,并且72℃持续1min。然而,本领域技术人员应了解这些参数可适当地变化。诱变的核酸接着被克隆至适当载体中,并且评估由诱变的核酸编码的多肽的活性。定点诱变可使用寡核苷酸定点诱变来实现以在任何克隆的所关注DNA中产生位点特异性突变。寡核苷酸诱变在本领域中有所描述(参看例如Reidhaar-Olson等人(1988)Science241:53-57)。简单地说,在所述程序中,合成多种待引入所克隆的DNA中的具有一种或多种突变的双链寡核苷酸并且插入至待诱变的所克隆的DNA(例如,编码P450多肽或P450杂合融合多肽的多核苷酸序列)中。回收含有诱变的DNA的克隆,并且评估其编码的多肽的活性。
用于产生变体的另一方法是装配PCR。装配PCR涉及由小DNA片段的混合物装配PCR产物。大量的不同PCR反应在同一小瓶中平行地发生,其中一种反应的产物引发另一反应的产物(参看美国专利5,965,408)。产生变体的另一方法是有性PCR诱变。在有性PCR诱变中,基于序列同源性在体外由于DNA分子的随机发酵而产生的不同但高度相关的DNA序列的DNA分子之间发生强制同源重组。这之后是在PCR反应中通过引物延伸固定所述杂交。有性PCR诱变描述于本领域中已知的公布中(参看例如Stemmer(1994)Proc.Natl.Acad.Sci.U.S.A.91:10747-10751)。变体也可通过体内诱变产生。在一些实施方案中,核酸序列中的随机突变通过在如大肠杆菌菌株的细菌菌株中增殖所述序列而产生,所述细菌菌株携带在一个或多个DNA修复途径中的突变。所述突变基因菌株具有高于野生型菌株的随机突变率的随机突变率。在这些菌株之一中增殖DNA序列(例如编码P450杂合融合多肽的多核苷酸序列)将最终产生在所述DNA内的随机突变。适用于体内诱变的突变基因菌株描述于本领域中的公布(参看例如国际专利申请公布号WO1991/016427)中。变体也可使用盒式诱变来产生。在盒式诱变中,双链DNA分子的小区域被不同于原生序列的合成寡核苷酸盒置换。所述寡核苷酸通常含有完全和/或部分随机化原生序列。递归整体诱变(Recursive ensemble mutagenesis)也可用于产生变体。递归整体诱变是用于蛋白工程改造(即,蛋白诱变)的算法,所述算法被开发用以产生表型相关突变体的各种群体,其成员的氨基酸序列不同。这种方法使用反馈机制来控制连续数轮的组合盒式诱变(参看例如Arkin等人(1992)Proc.Natl.Acad.Sci.,U.S.A.89:7811-7815)。在一些实施方案中,变体使用指数整体诱变(Exponential ensemble mutagenesis)来产生。指数整体诱变是一种用于产生具有高百分比的独特并且功能性突变体的组合文库的方法,其中小组的残基平行地随机化以在各改变的位置处标识产生功能性蛋白的氨基酸(参看例如Delegrave等人(1993)Biotech.Res.11:1548-1552)。在一些实施方案中,变体使用改组程序来产生,其中编码不同多肽的多种核酸的部分融合在一起以产生编码嵌合多肽的嵌合核酸序列(如例如美国专利号5,965,408和5,939,250中所述)。
基序和结构
CYP153A(G307A)突变体的鉴定和表征描述于Honda Malca等人(上文)中,其中作者调查了CYP153A中的潜在的底物相互作用残基。Honda Malca等人执行了基于结构的分析,所述分析集中于鉴定结构元件中含有侧链指向血红素中心的氨基酸且因此预期在活性氧的攻击期间与每一个底物分子接触的关键残基。为此,位置G307被鉴定为两个热点位置之一,其可由蛋白质结构鉴定,且其还为先前描述的针对CYP153A6建立的同源模型的活性位点的一部分。相比之下,本公开是基于产生随机突变以尝试改进产物输出(参看关于如下文表5-11所示的饱和文库的实施例)。例如,变体SEQ ID NO:98是基于SEQ ID NO:38(具有G307A和A796V突变)并且具有另外突变,包括Q12W、R27L、K119R、S140N、S157R、V159M、S233L和A244R,所述突变基于三维建模均未位于CYP153A结构域的活性位点中(参看图6)。
CYP153A是球状蛋白并且其催化活性位点涉及与血红素基团相邻的氨基酸残基,其中发生底物羟基化的化学反应。图5描绘了与所述CYP153A-还原酶杂合融合多肽内的还原酶结构域相邻的CYP153A催化结构域。位置G307与活性位点中的血红素紧密接近。然而,本公开显示出当未必在所述蛋白质的活性位点中的特定位置发生突变时,CYP153A的催化特性可经过改进,例如位置SEQ ID NO:38的12、27、28、119、141、157、159、231、233和244;位置SEQ ID NO:38的12、28、119、140、157、159、233、244、254和407;位置SEQ ID NO:38的12、27、111、119、141、157、159、231、233、244和254;位置SEQ ID NO:38的12、28、119、140、149、157、159、231、233和407;位置SEQ ID NO:38的12、27、28、119、140、157、159、233、244和407;位置SEQ ID NO:38的10、11、12、28、119、141、159、231、233、244和407;位置SEQ ID NO:38的11、12、27、28、119、141、157、159、197、231、233、244、407和477;位置SEQ ID NO:38的11、12、28、119、141、157、159、197、231、233、244和407;和/或位置SEQ ID NO:38的11、12、27、28、119、141、149、157、159、231、233和407。改进催化特性的特定变体的实例为Q12W、R27L、Q28M、K119R、V141T、S157R、V159M、A231Y、S233L、A244R(SEQ ID NO:166);Q12W、Q28M、K119R、S140N、S157R、V159M、S233L、A244R、R254G、N407G(SEQ ID NO:168);Q12W、R27L、F111A、K119R、V141T、S157R、V159M、A231Y、S233L、A244R、R254G(SEQ ID NO:170);Q12W、Q28M、K119R、S140N、P149G、S157R、V159M、A231Y、S233L、N407G(SEQ ID NO:172);Q12W、R27L、Q28M、K119R、S140N、S157R、V159M、S233L、A244R、N407G(SEQ ID NO:174);D10Y、I11L、Q12W、Q28M、K119R、V141T、V159M、A231Y、S233L、A244R、N407G(SEQ ID NO:176);I11L、Q12W、R27L、Q28M、K119R、V141T、S157R、V159M、A197T、A231Y、S233L、A244R、N407G、P477G(SEQ IDNO:178);I11L、Q12W、Q28M、K119R、V141T、S157R、V159M、A197T、A231Y、S233L、A244R、N407G(SEQ ID NO:180);和I11L、Q12W、R27L、Q28M、K119R、V141T、P149G、S157R、V159M、A231Y、S233L、N407G(SEQ ID NO:182)。
宿主细胞
通过重组宿主细胞增加ω-OH脂肪酸组合物的产生的策略包括通过在生产宿主中表达CYP153A-还原酶杂合融合基因和硫酯酶基因而增加的通过脂肪酸生物合成途径的通量。如本文所用,术语重组宿主细胞或经过工程改造的宿主细胞是指遗传组成已经例如通过有意引入新的遗传元件和/或有意修饰天然存在于宿主细胞中的遗传元件而相对于相应野生型宿主细胞发生改变的宿主细胞。所述重组宿主细胞的后代也含有这些新的和/或经过修饰的遗传元件。在本文所述的本公开的任何方面,所述宿主细胞可选自植物细胞、昆虫细胞、真菌细胞(例如,丝状真菌,如假丝酵母属种,或芽殖酵母,如酵母属种)、藻类细胞和细菌细胞。在一个实施方案中,重组宿主细胞为重组微生物。作为微生物的宿主细胞的实例包括但不限于来自埃希氏菌属、杆菌属、乳杆菌属、发酵单胞菌属、红球菌属、假单胞菌属、曲霉属、木霉属、脉孢菌属、镰孢属、腐质霉属、根毛霉属、克鲁维酵母属、毕赤酵母属、毛霉菌属、毁丝霉属、青霉属、平革菌属、侧耳属、栓菌属、金孢子菌属、酵母属、窄食单胞菌属、裂殖酵母属、亚罗酵母属或链霉菌属的细胞。在一些实施方案中,宿主细胞为革兰氏阳性细菌细胞。在其它实施方案中,宿主细胞为革兰氏阴性细菌细胞。在一些实施方案中,宿主细胞为大肠杆菌细胞。在一些实施方案中,宿主细胞为大肠杆菌B细胞、大肠杆菌C细胞、大肠杆菌K细胞或大肠杆菌W细胞。在其它实施方案中,宿主细胞为迟缓芽孢杆菌细胞、短芽孢杆菌细胞、嗜热脂肪芽孢杆菌细胞、地衣芽孢杆菌细胞、嗜碱芽孢杆菌细胞、凝结芽胞杆菌细胞、环状芽孢杆菌细胞、短小芽孢杆菌细胞、苏云金芽孢杆菌细胞、克劳氏芽孢杆菌细胞、巨大芽孢杆菌细胞、枯草芽孢杆菌细胞或解淀粉芽孢杆菌细胞。在其它实施方案中,宿主细胞为康氏木霉细胞、绿色木霉细胞、里氏木霉细胞、长梗木霉细胞、泡盛曲霉细胞、烟曲霉细胞、臭曲霉细胞、构巢曲霉细胞、黑曲霉细胞、米曲霉细胞、特异腐质霉细胞、柔毛腐质霉细胞、浑浊红球菌细胞、米黑根毛霉细胞或米黑毛酶细胞。在其它实施方案中,宿主细胞为变铅青链霉菌细胞或鼠灰链霉菌细胞。在其它实施方案中,宿主细胞为放线菌细胞。在一些实施方案中,宿主细胞为酿酒酵母细胞。
在其它实施方案中,宿主细胞为真核植物细胞、藻类细胞、蓝藻菌细胞、绿色硫细菌细胞、绿色非硫细菌细胞、紫色硫细菌细胞、紫色非硫细菌细胞、嗜极生物细胞、酵母细胞、真菌细胞、本文所述的生物或合成生物中任一者的经过工程改造的细胞。在一些实施方案中,宿主细胞为光依赖性的或固定碳。在一些实施方案中,宿主细胞具有自养活性。在一些实施方案中,宿主细胞具有光合自养活性,如在光存在下。在一些实施方案中,宿主细胞在光不存在下为异养性或混合营养的。在某些实施方案中,宿主细胞为来自拟南芥、柳枝稷、巨芒、玉米、布朗葡萄藻、莱茵衣藻、盐生杜氏藻、聚球蓝细菌属种PCC 7002、聚球蓝细菌属种PCC 7942、集胞藻属种PCC 6803、细长嗜热聚球藻BP-1、微温绿菌、橙色绿屈挠菌、酒色着色菌、深红红螺菌、荚膜红细菌、沼泽红假单胞菌、扬氏梭菌、热纤梭菌、产黄青霉菌、毕赤酵母、酿酒酵母、粟酒裂殖酵母、荧光假单胞菌或运动发酵单胞菌的细胞。在一个实施方案中,微生物细胞来自蓝细菌,包括但不限于原绿球藻、聚球藻、集胞藻、蓝杆藻和念珠藻。在另一实施方案中,微生物细胞来自特定蓝细菌物种,包括但不限于细长聚球藻PCC7942、集胞藻属种PCC6803和聚球藻属种PCC7001。
表达载体
在一些实施方案中,经由重组载体向宿主细胞提供多核苷酸(或基因)序列,所述重组载体包括可操作性连接于所述多核苷酸序列的启动子。在某些实施方案中,所述启动子为发育调控启动子、细胞器特异性启动子、组织特异性启动子、诱导型启动子、组成型启动子或细胞特异性启动子。在一些实施方案中,所述重组载体包括选自以下的至少一个序列:可操作性偶合于多核苷酸序列的表达控制序列;可操作性偶合于多核苷酸序列的选择标记;可操作性偶合于多核苷酸序列的标记序列;可操作性偶合于多核苷酸序列的纯化部分;可操作性偶合于多核苷酸序列的分泌序列;和可操作性偶合于多核苷酸序列的靶向序列。本文所述的表达载体包括呈适用于多核苷酸序列在宿主细胞中的表达的形式的多核苷酸序列。本领域技术人员应了解,所述表达载体的设计可取决于如待转化的宿主细胞的选择、所需多肽的表达水平等的因素。本文所述的表达载体可引入宿主细胞中以产生由如上文所述(上文)的多核苷酸序列编码的多肽,包括融合多肽。编码多肽的基因在例如大肠杆菌的原核生物中的表达最通常用含有组成型或诱导型启动子的载体进行,所述启动子指导融合或非融合多肽的表达。融合载体将多个氨基酸添加至其中编码的多肽,通常至所述重组多肽的氨基或羧基端。所述融合载体典型地用于以下三种目的中的一者或多者,包括增加重组多肽的表达;增加重组多肽的溶解度;和通过充当亲和纯化中的配体来帮助纯化重组多肽。通常,在融合表达载体中,蛋白水解裂解位点被引入融合部分与重组多肽的接合点处。这允许在融合多肽的纯化后分离重组多肽与融合部分。所述酶和其同源识别序列的实例包括因子Xa、凝血酶和肠激酶。示例性融合表达载体包括pGEX载体(Pharmacia Biotech,Inc.,Piscataway,NJ;Smith等人(1988)Gene 67:31-40)、pMAL载体(New EnglandBiolabs,Beverly,MA)和pRITS载体(Pharmacia Biotech,Inc.,Piscataway,N.J.),所述载体分别使谷胱甘肽S-转移酶(GST)、麦芽糖E结合蛋白或蛋白A融合至靶标重组多肽。
诱导性、非融合大肠杆菌表达载体的实例包括pTrc载体(Amann等人(1988)Gene69:301-315)和pET 11d载体(Studier等人,Gene Expression Technology:Methods inEnzymology 185,Academic Press,San Diego,Calif.(1990)60-89)。pTrc载体的靶标基因表达依赖于来自杂合trp-lac融合启动子的宿主RNA聚合酶转录。pET 11d载体的靶标基因表达依赖于由共同表达的病毒RNA聚合酶(T7gn1)介导的来自T7gn10-lac融合启动子的转录。这种病毒聚合酶由如BL21(DE3)或HMS174(DE3)的宿主菌株在lacUV 5启动子的转录控制下从含有T7gn1基因的常驻λ原噬菌体提供。用于原核和真核细胞的合适表达系统是本领域中众所周知的(参看例如Sambrook等人(1989)Molecular Cloning:A LaboratoryManual,第2版,Cold Spring Harbor Laboratory)。诱导性、非融合大肠杆菌表达载体的实例包括pTrc载体(Amann等人(1988)Gene 69:301-315)和PET 11d载体(Studier等人(1990)Gene Expression Technology:Methods in Enzymology 185,Academic Press,SanDiego,CA,第60-89页)。在某些实施方案中,本公开的多核苷酸序列可操作性连接于来源于噬菌体T5的启动子。在一个实施方案中,所述宿主细胞为酵母细胞。在这个实施方案中,所述表达载体为酵母表达载体。载体可经由多种用于将外来核酸(例如DNA)引入宿主细胞中的本领域公认技术引入原核或真核细胞中。用于转化或转染宿主细胞的合适方法可在例如Sambrook等人(上文)中找到。对于细菌细胞的稳定转化,已知(视所用的表达载体和转化技术而定)某一部分的细胞将吸收并且复制所述表达载体。为了鉴定并且选择这些转化体,编码可选标记的基因(例如,抗生素抗性)可连同所关注的基因被引入至宿主细胞中。可选标记包括赋予对如但不限于氨苄青霉素、卡那霉素、氯霉素或四环素的药物的抗性的那些。编码可选标记的核酸可被引入宿主细胞中与编码本文所述的多肽的载体相同的载体上,或可被引入至独立载体上。
任选的途径工程改造
本公开的宿主细胞或微生物包括遗传上经过工程改造或修饰以含有改变以便测试特异性突变对酶活性的效率的宿主菌株或宿主细胞(即,重组细胞或微生物)。多种任选的遗传操纵和改变可从一种宿主细胞至另一宿主细胞互换地使用,取决于哪种原生酶途径存在于初始宿主细胞中。在一个实施方案中,宿主菌株可用于测试与其它生物合成多肽(例如酶)组合的CYP153A-还原酶杂合融合多肽变体的表达。宿主菌株可涵盖多种遗传改变以便测试具体变量,包括但不限于培养条件,包括发酵组分、碳源(例如原料)、温度、压力、减少的培养物污染条件和氧水平。
在一个实施方案中,宿主菌株涵盖任选的fadE和fhuA缺失。酰基-CoA脱氢酶(FadE)是对于使脂肪酸代谢来说重要的酶。其催化脂肪酸利用(β-氧化)中的第二步骤,所述第二步骤是使脂肪酸(酰基-CoA)的长链断裂成乙酰基-CoA分子的过程。更具体说来,细菌中脂肪酸降解的β-氧化周期的第二步骤是将酰基-CoA氧化为2-烯酰基-CoA,所述氧化由FadE催化。当大肠杆菌缺乏FadE时,其无法依靠脂肪酸作为碳源生长,但其可依靠乙酸盐生长。不能利用任何链长的脂肪酸与所报道的fadE菌株的表型(即,其中FadE功能受到破坏的fadE突变型菌株)一致。所述fadE基因可任选地敲除或减弱以确保可作为脂肪酸衍生物途径中的中间物的酰基-CoA可积聚于细胞中,使得所有酰基-CoA均可有效地转化为脂肪酸衍生物。然而,当糖用作碳源时,fadE减弱是任选的,因为在所述条件下,FadE的表达有可能受到抑制并且FadE因此可仅少量存在并且无法有效地与酯合酶或其它酶竞争酰基-CoA底物。FadE由于分解代谢产物抑制作用而受到抑制。大肠杆菌和多种其它微生物相比脂肪酸偏好消耗糖,因此当两种来源均可获得时,糖首先通过抑制fad调节子而被消耗(参看D.Clark,JBacteriol.(1981)148(2):521-6))。此外,糖的不存在和脂肪酸的存在会诱导FadE表达。酰基-CoA中间物可能不再属于β氧化途径,因为由fad调节子表达的蛋白质(包括FadE)被上调并且将有效地竞争酰基-CoA。因此,使fadE基因敲除或减弱可为有益的。由于大多数碳源主要基于糖,所以任选地减弱FadE。基因fhuA编码TonA蛋白,所述蛋白是大肠杆菌的外膜中的能量偶合转运蛋白和受体(V.Braun(2009)J Bacteriol.191(11):3431–3436)。其缺失是任选的。所述fhuA缺失使细胞对噬菌体侵袭更具抵抗性,其在某些发酵条件下可为有益的。因此,在可能在发酵运行中经受潜在污染的宿主细胞中可能期望缺失fhuA。
在另一实施方案中,宿主菌株(上文)还涵盖以下基因中的一者或多者的任选的过表达,所述基因包括fadR、fabA、fabD、fabG、fabH、fabV和/或fabF。所述基因的实例是来自大肠杆菌的fadR、来自鼠伤寒沙门氏菌的fabA(NP_460041)、来自鼠伤寒沙门氏菌的fabD(NP_460164)、来自鼠伤寒沙门氏菌的fabG(NP_460165)、来自鼠伤寒沙门氏菌的fabH(NP_460163)、来自霍乱弧菌的fabV(YP_001217283)和来自丙酮丁醇梭菌的fabF(NP_350156)。编码脂肪酸生物合成中的酶和调节因子的这些基因中的一者或多者的过表达可用于增加在多种培养条件下包括ω-OH脂肪酸和其衍生物的脂肪酸衍生物化合物的效价。
在另一实施方案中,大肠杆菌菌株用作用于产生ω-OH脂肪酸和其衍生物的宿主细胞。同样,这些宿主细胞提供一种或多种生物合成基因(即,编码脂肪酸生物合成的酶和调节因子的基因)的任选的过表达,所述过表达可进一步增加或增强在多种培养条件下如脂肪酸衍生物(例如,ω-OH脂肪酸和α,ω-二酸等)的脂肪酸衍生物化合物的效价,所述基因包括但不限于fadR、fabA、fabD、fabG、fabH、fabV和/或fabF。遗传改变的实例包括来自大肠杆菌的fadR、来自鼠伤寒沙门氏菌的fabA(NP_460041)、来自鼠伤寒沙门氏菌的fabD(NP_460164)、来自鼠伤寒沙门氏菌的fabG(NP_460165)、来自鼠伤寒沙门氏菌的fabH(NP_460163)、来自霍乱弧菌的fabV(YP_001217283)和来自丙酮丁醇梭菌的fabF(NP_350156)。在一些实施方案中,携带这些生物合成基因的合成操纵子可进行工程改造并且在细胞中表达以便在多种培养条件下测试P450表达和/或进一步增强ω-OH脂肪酸和α,ω-二酸产生。所述合成操纵子含有一种或多种生物合成基因。经过工程改造的操纵子可含有任选的脂肪酸生物合成基因,包括来自霍乱弧菌的fabV、来自鼠伤寒沙门氏菌的fabH、来自鼠伤寒沙门氏菌的fabD、来自鼠伤寒沙门氏菌的fabG、来自鼠伤寒沙门氏菌的fabA和/或来自丙酮丁醇梭菌的fabF,其可用于促进脂肪酸衍生物的过表达以便测试具体培养条件。所述合成操纵子的一种优势是ω-OH脂肪酸衍生物产生的速率可进一步增加或增强。
在一些实施方案中,用于表达ACP和生物合成酶(例如ω-羟化酶、硫酯酶等)的宿主细胞或微生物将进一步表达涵盖某些酶活性的基因,所述酶活性可增加如ω-OH脂肪酸、ω-OH脂肪酸衍生物、α,ω-二酸等的一种或多种特定脂肪酸衍生物的产生。在一个实施方案中,所述宿主细胞具有用于脂肪酸产生的硫酯酶活性(E.C.3.1.2.*或E.C.3.1.2.14或E.C.3.1.1.5),所述产生可通过过表达所述基因来增加。在另一实施方案中,所述宿主细胞具有用于脂肪酯产生的酯合酶活性(E.C.2.3.1.75)。在另一实施方案中,所述宿主细胞具有用于脂肪醇产生的酰基-ACP还原酶(AAR)(E.C.1.2.1.80)活性和/或醇脱氢酶活性(E.C.1.1.1.1.)和/或脂肪醇酰基-CoA还原酶(FAR)(E.C.1.1.1.*)活性和/或羧酸还原酶(CAR)(EC 1.2.99.6)活性。在另一实施方案中,所述宿主细胞具有用于脂肪醛产生的酰基-ACP还原酶(AAR)(E.C.1.2.1.80)活性。在另一实施方案中,所述宿主细胞具有用于烷烃和烯烃产生的酰基-ACP还原酶(AAR)(E.C.1.2.1.80)活性和脱羰基酶(ADC)活性。在另一实施方案中,所述宿主细胞具有用于脂肪醇产生的酰基-CoA还原酶(E.C.1.2.1.50)活性、酰基-CoA合酶(FadD)(E.C.2.3.1.86)活性和硫酯酶(E.C.3.1.2.*或E.C.3.1.2.14或E.C.3.1.1.5)活性。在另一实施方案中,所述宿主细胞具有用于脂肪酯产生的酯合酶活性(E.C.2.3.1.75)、酰基-CoA合酶(FadD)(E.C.2.3.1.86)活性和硫酯酶(E.C.3.1.2.*或E.C.3.1.2.14或E.C.3.1.1.5)活性。在另一实施方案中,所述宿主细胞具有用于酮产生的OleA活性。在另一实施方案中,所述宿主细胞具有用于内部烯烃产生的OleBCD活性。在另一实施方案中,所述宿主细胞具有用于脂肪醇产生的酰基-ACP还原酶(AAR)(E.C.1.2.1.80)活性和醇脱氢酶活性(E.C.1.1.1.1.)。在另一实施方案中,所述宿主细胞具有用于制备末端烯烃的硫酯酶(E.C.3.1.2.*或E.C.3.1.2.14或E.C.3.1.1.5)活性和脱羧酶活性。微生物和微生物细胞中酶活性的表达由美国专利号8,097,439;8,110,093;8,110,670;8,183,028;8,268,599;8,283,143;8,232,924;8,372,610;和8,530,221教示,所述专利以引用的方式并入本文。在其它实施方案中,用于表达ACP和其它生物合成酶的宿主细胞或微生物将包括某些原生酶活性,所述酶活性上调或过表达以便产生如ω-OH脂肪酸、ω-OH脂肪酸衍生物和α,ω-二酸的一种或多种特定脂肪酸衍生物。在一个实施方案中,所述宿主细胞具有用于脂肪酸产生的原生硫酯酶(E.C.3.1.2.*或E.C.3.1.2.14或E.C.3.1.1.5)活性,所述产生可通过过表达所述硫酯酶基因来增加。
本公开包括表达编码CYP153A-还原酶杂合融合多肽变体和其它生物合成酶(上文)的基因的宿主菌株或微生物。所述重组宿主细胞产生如ω-OH脂肪酸、ω-OH脂肪酸衍生物、α,ω-二酸和其组合物和共混物的脂肪酸衍生物。所述脂肪酸衍生物典型地从培养基回收和/或与宿主细胞分离。在一个实施方案中,所述脂肪酸衍生物从培养基回收(细胞外)。在另一实施方案中,所述脂肪酸衍生物与宿主细胞分离(细胞内)。在另一实施方案中,所述脂肪酸衍生物从培养基回收并且与宿主细胞分离。由宿主细胞产生的脂肪酸衍生物或组合物可使用所属领域中已知的方法(例如GC-FID)进行分析,以便确定特定脂肪酸衍生物的分布以及如ω-OH脂肪酸、ω-OH脂肪酯、α,ω-二酸等的ω-OH脂肪酸衍生物的组分的链长和饱和程度。
培养和发酵
如本文所用,术语发酵广泛地是指通过宿主细胞将有机材料转化为靶标物质,例如通过使重组宿主细胞的培养物在包含碳源的培养基中增殖而通过重组宿主细胞将碳源转化为ω-OH脂肪酸或其衍生物。所述许可产生的条件是指允许宿主细胞产生如ω-OH脂肪酸的所需产物的任何条件。同样,其中载体的多核苷酸序列表达的一种或多种条件意指允许宿主细胞合成多肽的任何条件。合适的条件包括例如发酵条件。发酵条件可包括多种参数,包括但不限于温度范围、充气水平、进料速率和培养基组成。这些条件中的每一者个别地并且组合地允许宿主细胞生长。发酵可为需氧的、厌氧的或其变化形式(如微需氧的)。示例性培养基包括培养液或凝胶。一般来说,培养基包括可由宿主细胞直接代谢的碳源。另外,酶可用于培养基中以促进碳源的动员(例如,淀粉或纤维素解聚为可发酵糖)和后续代谢。
对于小规模生产,经过工程改造的宿主细胞可在例如约100μL、200μL、300μL、400μL、500μL、1mL、5mL、10mL、15mL、25mL、50mL、75mL、100mL、500mL、1L、2L、5L或10L的批料中生长;发酵;并且被诱导表达所需的多核苷酸序列,如编码P450杂合融合多肽的多核苷酸序列。关于大规模生产,经过工程改造的宿主细胞可在约10L、100L、1000L、10,000L、100,000L和1,000,000L或更大的批料中生长;发酵;并且被诱导表达所需的多核苷酸序列。或者,可进行大规模分批进料发酵。如本文所述的ω-OH脂肪酸、其衍生物和组合物在重组宿主细胞培养物的细胞外环境中发现并且可容易地与培养基分离。ω-OH脂肪酸或其衍生物可由重组宿主细胞分泌,转运至细胞外环境中或被动地转移至重组宿主细胞培养物的细胞外环境中。所述ω-OH脂肪酸或其衍生物使用所属领域中已知的常规方法与重组宿主细胞培养物分离。
来源于重组宿主细胞的产品
如本文所用,现代碳分数(fraction of modem carbon)或fM具有如由美国国家标准与技术研究所(NIST)标准参考材料(SRM 4990B和4990C,分别称作草酸标准物HOxI和HOxII所定义的相同含义。所述基础定义涉及14C/12C同位素比率HOxI的0.95倍(参考AD1950)。这与衰变校正的工业革命前树木(decay-corrected pre-Industrial Revolutionwood)大致相等。对于当前的活生物圈(植物材料),fM大约为1.1。生物产品(例如,根据本公开产生的脂肪酸衍生物,包括ω-OH脂肪酸和衍生物)包括以生物学方式产生的有机化合物。特别地,使用本文的脂肪酸生物合成途径产生的脂肪酸衍生物(例如,ω-OH脂肪酸和其衍生物)尚未由可再生来源产生并且因而是新的物质组合物。这些新的生物产品可基于双重碳-同位素指纹图谱或14C定年与来源于石化碳的有机化合物区分。另外,生物来源的碳(例如葡萄糖对甘油)的具体来源可通过双重碳-同位素指纹图谱确定(参看例如美国专利号7,169,588)。区分生物产品与基于石油的有机化合物的能力有益于在商业上追踪这些材料。例如,包括基于生物学和基于石油的碳同位素概况的有机化合物或化学品可与仅由基于石油的材料制成的有机化合物和化学品区分。因此,本文的生物产品可基于其独特的碳同位素概况在商业上进行跟踪或追踪。生物产品可通过比较各样品中的稳定碳同位素比率(13C/12C)而与基于石油的有机化合物区分。给定的生物产品中的13C/12C比率是大气二氧化碳中在二氧化碳固定时的13C/12C比率的结果。其也反映精确的代谢途径。也发生区域性变化。石油、C3植物(阔叶树)、C4植物(草本科植物)和海相碳酸盐均在13C/12C和相应的δ13C值方面显示显著差异。此外,由于代谢途径的原因,C3和C4植物的脂质物质的分解与来源于相同植物的碳水化合物组分的材料不同。在测量的精密度内,13C由于同位素分馏效应显示大的变化,其中对于生物产品来说最显著的是光合作用机制。植物中碳同位素比率差异的主要原因与植物中光合作用碳代谢途径的差异密切相关,尤其是在初级羧化期间所发生的反应(即,大气CO2的最初固定)。两大类植物是包含C3(或Calvin-Benson)光合循环的那些和包含C4(或Hatch-Slack)光合循环的那些。在C3植物中,初级CO2固定或羧化反应涉及酶核酮糖-1,5-二磷酸羧化酶,并且第一种稳定产物是3-碳化合物。如硬木和针叶树的C3植物主要在温带气候区。在C4植物中,涉及另一种酶磷酸烯醇-丙酮酸羧化酶的另外羧化反应是初级羧化反应。第一种稳定碳化合物是4-碳酸,其随后脱去羧基。由此释放的CO2由C3循环再固定。C4植物的实例是热带牧草、玉米和甘蔗。C4和C3植物展现一定范围的13C/12C同位素比率,但典型的值对于C4植物为约-7至约-13千分率并且对于C3植物为约-19至约-27千分率(参看例如Stuiver等人(1977)Radiocarbon 19:355)。煤和石油一般落在这后一个范围内。13C测量标度最初是通过以皮迪箭石(PDB)石灰岩设定为零来定义,其中值以与这种材料的偏差的千分数给出。δ13C值以千分数(千分率)表述,缩写为‰,并且如下计算:
δ13C(‰)=[(13C/12C)样品-(13C/12C)标准物]/(13C/12C)标准物×1000
由于PDB参考材料(RM)已经耗尽,与IAEA、USGS、NIST和其它所选择的国际同位素实验室合作开发出了一系列的替代RM。用于与PDB的千分率偏差的符号为δ13C。通过高精密度的稳定比率质谱分析(IRMS)在质量为44、45和46的分子离子上对CO2进行测量。本文所述的组合物包括通过任何本文所述的方法产生的生物产品,包括例如脂肪酸衍生物产品。具体说来,所述生物产品可具有约-28或更大、约-27或更大、-20或更大、-18或更大、-15或更大、-13或更大、-10或更大或-8或更大的δ13C。例如,所述生物产品可具有约-30至约-15、约-27至约-19、约-25至约-21、约-15至约-5、约-13至约-7或约-13至约-10的δ13C。在其它情况下,所述生物产品可具有约-10、-11、-12或-12.3的δ13C。本文中根据本文的公开产生的生物产品也可通过比较各化合物中14C的量来与基于石油的有机化合物区分。因为14C具有5730年的核半衰期,含有较老的碳的基于石油的燃料可与含有较新的碳的生物产品区分(参看例如Currie,Source Apportionment of Atmospheric Particles,Characterization ofEnvironmental Particles,J.Buffle和H.P.van Leeuwen编,IUPAC EnvironmentalAnalytical Chemistry Series第I卷的1(Lewis Publishers,Inc.)3-74,(1992))。关于放射性碳定年的基本假定是大气中14C浓度的恒定性引起活生物中14C的恒定性。然而,由于自1950年以来的大气核测试和自1850年以来的化石燃料燃烧,14C已经获得第二、地球化学时间特征。在20世纪60年代中期,在核测试高峰期,其在大气CO2中并因此在活生物圈中的浓度大约增加了一倍。此后它逐渐返回至约1.2×10-12的稳态宇宙成因(大气)基线同位素比率(14C/12C),具有7-10年的近似弛豫“半衰期”。这后一种半衰期绝对不能按字面意思理解;相反,人们必须使用详细的大气核输入/衰变函数来追踪大气和生物圈中14C在核年代开始之后的变化。正是这后一种生物圈14C时间特征呈现出了对近代生物圈碳进行每年一次定年的希望。14C可通过加速器质谱(AMS)来测量,结果以现代碳分数(fM)为单位给出。fM由美国国家标准与技术研究所(NIST)标准参考材料(SRM)4990B和4990C定义。如本文所用,现代碳分数或fM具有如由美国国家标准与技术研究所(NIST)标准参考材料(SRM)4990B和4990C(分别称作草酸标准物HOxI和HoxII)所定义的相同含义。所述基础定义涉及14C/12C同位素比率HOxI的0.95倍(参考AD 1950)。这与衰变校正的工业革命前树木大致相等。关于当前的活生物圈(植物材料),fM大约为1.1。本文所述的组合物包括可具有至少约1的fM14C的生物产品。例如,本公开的生物产品可具有至少约1.01的fM14C、约1至约1.5的fM14C、约1.04至约1.18的fM14C或约1.111至约1.124的fM14C。
14C的另一种测量值被称作现代碳百分比(pMC)。对于使用14C定年的考古学家或地质学家,AD 1950等于零岁。这还表示100pMC。大气中的碳爆炸几乎达到1963年在热核武器高峰期的正常水平的两倍。其在大气中的分布已经从其出现开始计算近似值,针对从AD1950以来活的植物和动物显示大于100pMC的值。其随时间逐渐降低,现今的值接近107.5pMC。这意指如玉米的新鲜生物质材料将给出接近107.5pMC的14C签名。基于石油的化合物将具有pMC值零。组合化石碳与现代碳将引起现代pMC含量的稀释。通过假定107.5pMC表示现代生物质材料的14C含量并且0pMC表示基于石油的产品的14C含量,关于所述材料所测量的pMC值将反映两种组分类型的比例。例如,100%来源于现代大豆的材料将产生接近107.5pMC的放射性碳签名。如果所述材料用基于石油的产品稀释50%,那么其将产生大约54pMC的放射性碳签名。基于生物学的碳含量通过指定100%等于107.5pMC并且0%等于0pMC来推导。例如,测量出99pMC的样品将产生等效的基于生物学的碳含量93%。这个值被称作平均基于生物学的碳结果并且假定所分析材料内的所有组分均起源于现代生物材料或基于石油的材料。包含如本文所述的一种或多种脂肪酸衍生物的生物产品可具有至少约50、60、70、75、80、85、90、95、96、97、98、99或100的pMC。在其它情况下,本文所述的脂肪酸衍生物可具有介于约50与约100之间;介于约60与约100之间;介于约70与约100之间;介于约80与约100之间;介于约85与约100之间;介于约87与约98之间;或介于约90与约95之间的pMC。在其它情况下,本文所述的脂肪酸衍生物可具有约90、91、92、93、94或94.2的pMC。
实施例
以下具体实施例意图说明本公开并且不应解释为限制权利要求书的范围。
方案和方法
筛选文库
本文描述的所有方案均依赖用于使培养物生长的96孔板-master block-2mL系统(Greiner Bio-One,Monroe,NC or Corning,Amsterdam,The Netherlands),和用于从培养液提取脂肪酸物质的板(Costar,Inc.)。下文提供的方案是发酵条件的实施例。替代方案可用于评估脂肪酸物质产生。
32℃Plim培养方案
使用30μL LB培养物(来自在96孔板中生长的LB培养物)来接种290μL Plim培养基(表2),所述培养基接着在32℃振荡下孵育大约16小时。使用40μL过夜种子接种360μL Plim培养基。在32℃下生长持续2小时之后,所述培养物用IPTG(最终浓度1mM)(下表3)诱导。如果未另外注明,那么所述培养物接着在32℃下在振荡下孵育20小时,之后根据下文详述的标准提取方案提取所述培养物。
35℃Nlim培养方案
使用40μL LB培养物(来自在96孔板中生长的LB培养物)来接种360μL LB培养基(下表3),所述培养基接着在32℃振荡下孵育大约4小时。使用40μL LB种子接种360μL Nlim培养基。在35℃下在32℃下生长持续2小时之后,所述培养物用IPTG(最终浓度1mM)(下表3)诱导。如果未另外注明,那么所述培养物接着在35℃下在振荡下孵育20小时,之后根据下文详述的标准提取方案提取所述培养物。
表3:培养基名称和配方
脂肪酸物质标准提取方案
向欲进行提取的各孔中相继添加80μL 1M HCl、400μL乙酸丁酯(其中500mg/L十五烷醇作为内标)。所述96孔板接着使用板密封器(ALPS-300加热器;Abgene,ThermoScientific,Rockford,IL)进行热密封,并且使用MIXMATE混合器(Eppendorf,Hamburg,Germany)在2000rpm下振荡15分钟。在振荡之后,所述板在室温下在4500rpm下离心持续10分钟(Allegra X-15R,转子SX4750A,Beckman Coulter,Brea,CA)以分离水层和有机层。将100μL有机层被转移至96孔板(聚丙烯,Corning,Amsterdam,The Netherlands)并且用100uL BSTFA衍生化。所述板随后进行热密封并且存储于-20℃下直至使用如下进行的w-OH FFA方法通过GC-FID进行评估:将1μL样品注射至具有具1-20分流的火焰离子化检测器(FID)的Agilent 7890A GC Ultra装置(Agilent,Santa Clara,CA)中的分析柱(DB-1,10m×180μm×0.2μM膜厚度,可获自JW 121-101A)上。设置所述仪器以检测并且定量C10至C18脂肪酸和ω-羟基化脂肪酸。上文详述的方案表示标准条件,所述条件必要时可进行修改以优化分析结果。
建立易错文库
使用本领域技术人员已知的标准技术来制备易错文库。在一个实施例中,在载体中使用限制性核酸内切酶来制备载体骨架,同时在有利于并入错配的核苷酸的条件下通过PCR扩增从DNA模板产生DNA插入物的多样性的创建。在一种方法中,使用INFUSION克隆系统(Clontech Laboratories,Inc.,Mountain View,CA)根据制造商的方案执行载体骨架和具有多样性的DNA插入物的克隆。
建立饱和文库
使用本领域技术人员已知的标准技术来制备饱和文库。在一个实施例中,在载体中使用限制性核酸内切酶来制备载体骨架,同时使用简并引物产生DNA插入物的多样性的创建。在一种方法中,使用INFUSION克隆系统(Clontech Laboratories,Inc.,MountainView,CA)根据制造商的方案执行载体骨架和具有多样性的DNA插入物的克隆。
建立组合文库
组合被鉴定为有益的突变以提供具有ω-OH脂肪酸衍生物物质的产生的进一步改进的CYP153-还原酶杂合融合多肽变体(例如,杂合CYP153A-RedRhF蛋白变体)。使用本领域技术人员已知的标准技术来制备组合文库。在一个实施例中,在载体中使用限制性核酸内切酶来制备载体骨架,同时使用引入所需突变的引物产生DNA插入物的多样性的创建。如上文所述,在一种方法中,使用INFUSION克隆系统(Clontech Laboratories,Inc.,MountainView,CA)根据制造商的说明书执行载体骨架和具有多样性的DNA插入物的克隆。可使用转移PCR(tPCR)方案产生组合文库(Erijman等人(2011)J.Structural Bio.175:171-177)。
文库筛选
一旦在易错、饱和文库或组合文库中产生文库多样性,即使用上文所述方法之一对所述文库进行筛选。鉴定两种类型的命中:(1)增加量的ω-羟基脂肪酸(ω-OH FFA效价);和/或(2)增加的脂肪酸至ω-羟基脂肪酸转化。在各命中内所述杂合cyp153A-RedRhF蛋白变体的突变通过测序使用本领域技术人员常规使用的标准技术来识别。以下表5、6和7列出在饱和文库中被鉴定为有益的突变(命中)。
实施例1:用于文库筛选的菌株和质粒建构
这一实施例描述了针对饱和或组合诱变文库筛选建构的菌株和质粒。
如下产生编码由来自水油海杆菌的CYP153A(G307A)P450催化蛋白和来自红球菌属种NCIMB9784的P450RhF的c端含FMN和Fe/S还原酶结构域组成的杂合-融合蛋白的基因:由基因组DNA扩增cyp165A(G307A)_Maqu基因并且通过交叉PCR与密码子优化的合成P450RhF还原酶结构域融合。所得融合基因(SEQ ID NO:5)被克隆至pACYC-衍生物(即p15A复制子,卡那霉素抗性标记)中,使得其转录通过IPTG诱导型Ptrc启动子控制。所述质粒被命名为pEP125(参看表4,下文)。
编码杂合cyp153A(G307A)-Red450RhF融合蛋白的基因也由pEP125扩增并且被克隆至pCL1920源性载体(SC101复制子,大观霉素抗性标记物)中,使得其转录通过IPTG诱导型Ptrc启动子控制并且其形成具有编码植物硫酯酶(fatB1)、3-酮基-酰基-ACP合酶的变体(fabB)和转录调控因子(fadR)的操纵子。所述质粒被命名为pLC81(参看表4,下文)。
如下产生另外质粒:来自加州桂的编码植物硫酯酶(fatB1)的基因被合成为密码子优化的DNA并且被克隆至pCL1920源性载体(SC101复制子,大观霉素抗性标记)中,使得其转录通过IPTG诱导型Ptrc启动子控制并且其形成具有编码乙酰基-CoA羧化酶(accDACB)、生物素连接酶(birA)和酰基-载体蛋白的基因的操纵子。所述质粒被命名为pNH305(参看表4,下文)。质粒pAS033通过用来自拟南芥的密码子优化的合成植物硫酯酶(fatA3)置换pNH305中的fatB1而产生(参看表4,下文)。质粒pEP146通过用来自拟南芥的密码子优化的合成植物硫酯酶(fatA3)置换pLC81中的fatB1而产生(参看表4,下文)。pEP146也携带质粒编码的repA蛋白中的突变。
用于质粒转化的基础菌株是GLP077和BZ128。简单地说,如下操纵基础菌株GLPH077的基因组:使酰基-CoA脱氢酶(fadE)基因缺失并且使转录调控因子(fadR)和合成脂肪酸生物合成操纵子过表达。简单地说,如下操纵基础菌株BZ128的基因组:使fadE(酰基-CoA脱氢酶)基因缺失并且使合成脂肪酸生物合成操纵子、β-羟基脂肪酰基-ACP脱水酶(fabZ)和硫酯酶的变体(tesA)过表达。另外,所述菌株先前已经经受转座子以及N-甲基-N′-硝基-N-亚硝基胍(NTG)诱变和筛选。
表4:用于文库筛选的质粒
测试所述杂合cyp153A(G307A)-Red450RhF融合蛋白以了解宿主细胞中的表达是否可能产生ω-OH脂肪酸衍生物。表达SEQ ID NO:5的微生物能够由葡萄糖产生超过1g/L的ω-OH脂肪酸衍生物。因此,选择这种经过工程改造的酶用于进一步进化研究。
实施例2:cyp153A(G307A)-Red450RhF融合蛋白的P450催化结构域的饱和文库
建立cyp153A-Red450RhF融合蛋白的P450催化结构域的全饱和文库并且针对显示相比cyp153A(G307A)-Red450RhF(即,模板多肽)的改进的变体进行筛选。G307A(即,丙氨酸残基置换位置307中的甘氨酸)是改进cyp153A的ω-羟化酶活性的有益突变(参看HondaMalca等人(2012)Chem.Commun.48:5115)。关于命中的选择标准是(1)增加量的ω-羟基脂肪酸(ωOH FFA效价);和/或(2)增加的脂肪酸至ω-羟基脂肪酸转化。
使用本领域技术人员已知的标准技术来制备饱和文库。使用质粒pEP125和pLC81(参看表4,上文)来制备所述全饱和文库。对三种饱和文库进行筛选:对于第一种文库,pEP125与pNH305一起转化至菌株GLPH077中,对于第二种文库,pLC81转化至BZ128中,并且对于第三种文库,pEP125与pAS.033一起转化至GLPH077菌株中。所述第一和第二文库特别地针对ω-羟基十二烷酸形成中改进的变体进行筛选并且所述第三文库特别地针对ω-羟基十六碳烯酸形成中改进的变体进行筛选。所述文库使用上文所述的标准方案之一进行筛选。所述改进的变体显示于以下表5至7(下文)中。特别地,位置141的变体被鉴定多次并且被发现是用于ω-羟基十二烷酸和ω-羟基十六碳烯酸形成的显著改进的酶。
表5:来自cyp153A(G307A)-Red450RhF的催化结构域的第一位点饱和文库的改进变体的汇总。
FIOC=相比对照的改进倍数;对照是粗体。
表6:来自cyp153A(G307A)-Red450RhF的催化结构域的第二位点饱和文库的改进变体的汇总
FIOC=相比对照的改进倍数;对照是粗体。
表7:来自cyp153A(G307A)-Red450RhF的催化结构域的第三位点饱和文库的改进变体的汇总
FIOC=相比对照的改进倍数;对照是粗体。
实施例3:cyp153A(G307A)-Red450RhF融合蛋白的还原酶结构域的部分位点饱和文库
建立杂合cyp153A-Red450RhF融合蛋白的还原酶结构域的部分饱和文库(每第10个氨基酸发生突变)并且针对显示相比cyp153A(V141I,A231T,G307A)-Red450RhF(SEQ IDNO:32)(在催化P450cyp153A结构域的位点饱和诱变文库中识别的变体)的改进的变体进行筛选。关于命中的选择标准是(1)增加量的ω-羟基十二烷酸(ωOH FFA效价);和/或(2)增加的十二烷酸至ω-羟基十二烷酸转化。
使用本领域技术人员已知的标准技术来制备饱和文库。对于所述文库,具有cyp153A(V141I,A231T,G307A)-Red450RhF的pLC81被转化至BZ128中。所述文库使用上文所述的标准方案之一进行筛选。改进的变体显示于表8中。特别地,变体A796V(SEQ ID:42)和P666A是显著改进的酶。
表8:来自cyp153A(V141I A231T G307A)-Red450RhF的还原酶结构域的部分饱和文库的改进变体的概述
FIOC=相比对照的改进倍数;对照是粗体。
实施例4:cyp153A(G307A)-Red450RhF融合蛋白的还原酶结构域的组合文库
在所述还原酶结构域的部分饱和文库中鉴定的有益突变(实施例3)是组合文库进一步改进cyp153A(G307A)-Red450RhF融合蛋白的基础。选择标准是(1)增加量的ω-羟基十二烷酸(ωOH FFA效价);和/或(2)增加的十二烷酸至ω-羟基十二烷酸转化。
所述组合文库在具有cyp153A(V141I,A231T,G307A)-Red450RhF(SEQ ID:32)的pLC81中建构并且被转化至BZ128中。使用本领域技术人员已知的标准技术来制备组合文库。所述文库使用上文所述的标准方案之一进行筛选。改进的变体显示于下表9中。
表9:来自cyp153A(V141I,A231T,G307A)-Red450RhF的还原酶结构域的组合文库的改进变体的汇总
FIOC=相比对照的改进倍数;对照是粗体。
实施例5:cyp153A(G307A)-Red450RhF融合蛋白的催化和还原酶结构域的组合文库
在所述饱和文库中鉴定的有益突变(实施例2和3)是组合文库进一步改进cyp153A(G307A)-Red450RhF融合蛋白的基础。选择标准是(1)增加量的ω-羟基十二烷酸(ωOH FFA效价);和/或(2)增加的十二烷酸至ω-羟基十二烷酸转化。所述组合文库在pLC81中建构并且被转化至BZ128中。使用本领域技术人员已知的标准技术来制备组合文库。所述文库使用上文所述的标准方案之一进行筛选。最好的两种改进的变体显示于表10中。
表10:来自cyp153A(G307A)-Red450RhF的组合文库的最好的改进的变体
*48h后的效价(mg/L)
实施例6:cyp153A(G307A,A796V)-Red450RhF的位置141和309的位点饱和诱变
注意,位置141中的改变会影响底物特异性。因此,这两个位置的位点饱和诱变在cyp153A(G307A,A796V)-Red450RhF中进行。关于命中的选择标准是(1)增加量的ω-羟基十六碳烯酸;和/或(2)增加的十六碳烯酸至ω-羟基十六碳烯酸转化。
对于所述文库,具有cyp153A(G307A A796V)-Red450RhF(SEQ ID:38)的pEP146被转化至BZ128中。使用本领域技术人员已知的标准技术来制备位点饱和文库。所述文库使用上文所述的标准方案之一进行筛选。改进的变体显示于图2中。特别地,具有V141T(SEQ ID:46)的变体显示最高ω-羟基十六碳烯酸效价和最高的由十六碳烯酸的转化。
实施例7:cyp153A(G307A)-Red450RhF(A796V)融合蛋白的饱和文库
建立cyp153A-Red450RhF融合蛋白的全饱和文库并且针对显示相比cyp153A(G307A)-Red450RhF(A796V)(即,模板变体,SEQ ID NO:38)的改进的变体进行筛选。G307A(即,丙氨酸残基置换位置307中的甘氨酸)和A796V(即,缬氨酸残基置换位置796中的丙氨酸)是改进cyp153A的ω-羟化酶活性的有益突变(参看上文)。关于命中的选择标准是(1)增加量的ω-羟基脂肪酸(ω-OH FFA效价);和/或(2)增加的脂肪酸至ω-羟基脂肪酸的转化。
使用本领域技术人员已知的标准技术来制备饱和文库。使用质粒pEP302来制备全饱和文库,所述质粒是pEP146的衍生物(参看表4),其中基因的顺序发生改变(fatA3-fadB-fadR-cyp153A(G307A)-Red450RhF(A796V))并且最后一个基因由独立启动子表达。所述文库被转化至菌株stNH1525中。简单地说,如下操纵基础菌株stNH1525的基因组:fadE(酰基-CoA脱氢酶)基因缺失并且合成脂肪酸生物合成操纵子过表达。另外,所述菌株先前已经经受转座子以及N-甲基-N′-硝基-N-亚硝基胍(NTG)诱变和筛选。
所述文库使用上文所述的标准方案之一进行筛选。改进的变体显示于下表11中,特别地是显著改进ω-羟基十六烷酸和ω-羟基十六碳烯酸形成的变体。
表11:来自cyp153A(G307A)-Red450RhF(A976V)的位点饱和文库的改进变体的汇总
实施例8:cyp153A(G307A)-Red450RhF(A796V)融合蛋白的催化结构域的组合文库
在所述催化结构域的饱和文库中鉴定的有益突变(实施例7)是组合文库进一步改进cyp153A(G307A)-Red450RhF(A796V)融合蛋白的基础。关于命中的选择标准是(1)增加量的ω-羟基脂肪酸(ω-OH FFA效价);和/或(2)增加的脂肪酸至ω-羟基脂肪酸转化。
所述组合文库在具有cyp153A(G307A)-Red450RhF(A796A)(SEQ ID:38)的pEP302中建构并且被转化至stNH1525中。使用本领域技术人员已知的标准技术来制备组合文库。所述文库使用上文所述的标准方案之一进行筛选。改进的变体显示于下表12中,特别地是显著改进ω-羟基脂肪酸形成的变体。
表12:来自cyp153A(G307A)-Red450RhF(A796V)(SEQ ID NO:38)的催化结构域的组合文库的改进变体的汇总
实施例9:在高表达水平下的cyp153A(G307A)-Red450RhF(A796V)融合蛋白的催化结构域的组合文库
在所述催化结构域的组合文库中鉴定的有益突变(参看上文实施例8)是下一轮组合文库进一步改进cyp153A(G307A)-Red450RhF(A796V)融合蛋白的基础。关于命中的选择标准是(1)增加量的ω-羟基脂肪酸(ω-OH FFA效价);和/或(2)增加的脂肪酸至ω-羟基脂肪酸转化。
所述组合文库在具有在较高表达水平下的cyp153A(G307A)-Red450RhF(A796A)(SEQ ID:38)的pAA.016质粒(pEP302衍生物)中建构并且被转化至stNH1525中。使用本领域技术人员已知的标准技术来制备组合文库。所述文库使用上文所述的标准方案之一进行筛选。改进的变体显示于下表13中,特别地是显著改进ω-羟基脂肪酸形成的变体。
表13:来自cyp153A(G307A)-Red450RhF(A796V)的催化结构域的组合文库的改进变体的汇总
实施例10:cyp153A(G307A)-Red450RhF(A796V)融合蛋白的还原酶结构域的组合文库
在所述还原酶结构域的饱和文库中鉴定的有益突变(实施例7)是组合文库进一步改进cyp153A(G307A)-Red450RhF(A796V)融合蛋白的基础。选择标准是(1)增加量的ω-羟基脂肪酸(ω-OH FFA效价);和/或(2)增加的脂肪酸至ω-羟基脂肪酸转化。
所述组合文库在pEP302中建构并且被转化至stNH1525中。使用本领域技术人员已知的标准技术来制备组合文库。所述文库使用上文所述的标准方案之一进行筛选。改进的变体显示于表14中。
表14:来自cyp153A(G307A)-Red450RhF(A796V)的还原酶结构域的组合文库的改进变体
实施例11:cyp153A(Q12W,R27L,K119R,S140N,S157R,V159M,S233L,A244R,G307A)-Red450RhF(A796V)融合蛋白(SEQ ID:98)的催化结构域和还原酶结构域的组合文库
在所述催化结构域和还原酶结构域的组合文库中鉴定的有益突变(参看上文实施例8-10)是组合文库进一步改进cyp153A(Q12W,R27L,K119R,S140N,S157R,V159M,S233L,A244R,G307A)-Red450RhF(A796V)融合蛋白(SEQ ID NO:98)的基础。选择标准是(1)增加量的ω-羟基脂肪酸(ω-OH FFA效价);和/或(2)增加的脂肪酸至ω-羟基脂肪酸转化。
所述组合文库在具有cyp153A(Q12W,R27L,K119R,S140N,S157R,V159M,S233L,A244R,G307A)-Red450RhF(A796V)融合蛋白(SEQ ID NO:98)的pEP.333质粒(pEP302的衍生物)中建构(参看实施例7)并且被转化至stNH1525中。使用本领域技术人员已知的标准技术来制备组合文库。所述文库使用上文所述的标准方案之一进行筛选。
改进的变体显示于表15中。模板SEQ ID NO:98中的一些突变回复变异为野生型,如表15所示。例如,在表15所示的前述突变体中,S233L和A244R突变不再存在于变体SEQ IDNO:152中,而是添加新突变V141T和A231Y。
表15:来自cyp153A(Q12W,R27L,K119R,S140N,S157R,V159M,S233L,A244R,G307A)-Red450RhF(A796V)融合蛋白(SEQ ID NO:98)的催化结构域和还原酶结构域的组合文库的改进变体
实施例12:cyp153A(Q12W,R27L,K119R,S140N,S157R,V159M,S233L,A244R,G307A)-Red450RhF(A796V)融合蛋白(SEQ ID:98)的催化结构域的组合文库
在所述催化结构域的组合文库中鉴定的有益突变(参看上文实施例8)是组合文库进一步改进cyp153A(Q12W,R27L,K119R,S140N,S157R,V159M,S233L,A244R,G307A)-Red450RhF(A796V)融合蛋白SEQ ID NO:98的基础。选择标准是(1)增加量的ω-羟基脂肪酸(ω-OH FFA效价);和/或(2)增加的脂肪酸至ω-羟基脂肪酸转化。
所述组合文库在具有在较高表达水平下的cyp153A(Q12W,R27L,K119R,S140N,S157R,V159M,S233L,A244R,G307A)-Red450RhF(A796V)融合蛋白(SEQ ID NO:98)和具有硫酯酶fatA3和β-酮酰基-ACP合酶fabB的变体的第二操纵子的pEP.334质粒(pEP.333质粒的较低拷贝数衍生物)中建构(参看实施例11)。pEP344被转化至菌株AA.233中,所述菌株是菌株stNH1525(参看实施例7)的衍生物,具有组成性表达的调控蛋白fadR的变体。使用本领域技术人员已知的标准技术来制备组合文库。所述文库使用上文所述的标准方案之一进行筛选。改进的变体显示于表16中。模板SEQ ID NO:98中的一些突变回复变异为野生型,如表16所示。例如,在表16所示的第一突变体中,S140N突变不再存在于变体SEQ ID NO:166中,而是添加新突变Q28M、V141T和A231Y。
表16:来自cyp153A(Q12W,R27L,K119R,S140N,S157R,V159M,S233L,A244R,G307A)-Red450RhF(A796V)融合蛋白(SEQ ID NO:98)的催化结构域的组合文库的改进蛋白变体
如本领域技术人员显而易知,可进行以上方面和实施方案的多种修改和变化而不偏离本公开的精神和范围。所述修改和变化在本公开的范围内。
序列表
<110> REG生命科学有限责任公司
<120> 具有改进的特性的ω-羟化酶相关的融合多肽变体
<130> LS00054PCT3
<140>
<141>
<150> PCT/EP2015/079832
<151> 2015-12-15
<160> 184
<170> PatentIn 3.5版
<210> 1
<211> 1413
<212> DNA
<213> 水油海杆菌
<400> 1
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgg cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt taa 1413
<210> 2
<211> 470
<212> PRT
<213> 水油海杆菌
<400> 2
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Gly Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser
465 470
<210> 3
<211> 1413
<212> DNA
<213> 水油海杆菌
<400> 3
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt taa 1413
<210> 4
<211> 470
<212> PRT
<213> 水油海杆菌
<400> 4
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser
465 470
<210> 5
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 5
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggcgct gcgcctctaa 2400
<210> 6
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 6
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Ala Leu Arg Leu
785 790 795
<210> 7
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 7
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagct gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggcgct gcgcctctaa 2400
<210> 8
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 8
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Leu Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Ala Leu Arg Leu
785 790 795
<210> 9
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 9
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tgggacgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggcgct gcgcctctaa 2400
<210> 10
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 10
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Asp Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Ala Leu Arg Leu
785 790 795
<210> 11
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 11
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
atcgaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggcgct gcgcctctaa 2400
<210> 12
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 12
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Ile Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Ala Leu Arg Leu
785 790 795
<210> 13
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 13
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
caggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggcgct gcgcctctaa 2400
<210> 14
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 14
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Gln Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Ala Leu Arg Leu
785 790 795
<210> 15
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 15
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
ggggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggcgct gcgcctctaa 2400
<210> 16
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 16
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Gly Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Ala Leu Arg Leu
785 790 795
<210> 17
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 17
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
atggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggcgct gcgcctctaa 2400
<210> 18
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 18
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Met Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Ala Leu Arg Leu
785 790 795
<210> 19
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 19
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
ctggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggcgct gcgcctctaa 2400
<210> 20
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 20
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Leu Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Ala Leu Arg Leu
785 790 795
<210> 21
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 21
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
acggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggcgct gcgcctctaa 2400
<210> 22
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 22
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Thr Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Ala Leu Arg Leu
785 790 795
<210> 23
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 23
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc aaacaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggcgct gcgcctctaa 2400
<210> 24
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 24
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Asn Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Ala Leu Arg Leu
785 790 795
<210> 25
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 25
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggccgggat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggcgct gcgcctctaa 2400
<210> 26
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 26
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Arg Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Ala Leu Arg Leu
785 790 795
<210> 27
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 27
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcggcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggcgct gcgcctctaa 2400
<210> 28
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 28
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Ala Leu Arg Leu
785 790 795
<210> 29
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 29
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg ggcgtcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggcgct gcgcctctaa 2400
<210> 30
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 30
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Arg His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Ala Leu Arg Leu
785 790 795
<210> 31
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 31
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
atcgaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt acagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggcgct gcgcctctaa 2400
<210> 32
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 32
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Ile Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Thr Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Ala Leu Arg Leu
785 790 795
<210> 33
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 33
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagct gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tgggacgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
atggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc aaacaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcgcggat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggcgct gcgcctctaa 2400
<210> 34
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 34
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Leu Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Asp Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Met Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Asn Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Ala Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Ala Leu Arg Leu
785 790 795
<210> 35
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 35
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcggcggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggcgct gcgcctctaa 2400
<210> 36
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 36
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Ala Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Ala Leu Arg Leu
785 790 795
<210> 37
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 37
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 38
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 38
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 39
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 39
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaagtcct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcggacgg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 40
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 40
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Val Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Asp Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 41
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 41
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
atcgaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt acagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 42
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 42
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Ile Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Thr Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 43
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 43
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagct gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tgggacgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
atggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc aaacaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcgcggat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 44
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 44
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Leu Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Asp Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Met Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Asn Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Ala Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 45
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 45
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
acggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt acagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 46
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 46
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Thr Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Thr Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 47
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 47
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgaa ctgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 48
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 48
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asn Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 49
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 49
atgccaacac tgcccagaac atttgacgac atttggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 50
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 50
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Trp Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 51
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 51
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattcga tagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 52
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 52
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Asp Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 53
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 53
atgccaacac tgcccagaac atttgacgac attcagtcct tcctgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 54
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 54
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Phe Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 55
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 55
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
ttgacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 56
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 56
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Leu Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 57
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 57
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 58
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 58
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 59
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 59
atgccaacac tgcccagaac atttgacgac attcagaagc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 60
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 60
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Lys Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 61
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 61
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc ttcctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 62
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 62
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Phe Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 63
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 63
atgccaacac tgcccagaac atttgacgac attacgtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 64
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 64
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Thr Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 65
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 65
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggatcggagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 66
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 66
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Arg Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 67
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 67
atgccaacac tgcccagaac atttgactac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 68
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 68
Met Pro Thr Leu Pro Arg Thr Phe Asp Tyr Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 69
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 69
atgccaacac tgcccagaac atttgacgac attaggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 70
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 70
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Arg Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 71
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 71
atgccaacac tgcccagaac atttgacgac ttgcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 72
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 72
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Leu Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 73
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 73
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gacgattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 74
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 74
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Thr Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 75
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 75
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt tacgcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 76
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 76
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Tyr Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 77
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 77
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tccgctcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 78
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 78
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Arg Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 79
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 79
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 80
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 80
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 81
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 81
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatggt gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 82
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 82
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Gly Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 83
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 83
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggcaggg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 84
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 84
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Arg Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 85
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 85
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tcacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 86
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 86
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Ile
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 87
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 87
atgccaacac tgcccagaac atttaaggac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 88
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 88
Met Pro Thr Leu Pro Arg Thr Phe Lys Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 89
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 89
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 90
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 90
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 91
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 91
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcattgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 92
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 92
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Leu Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 93
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 93
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcgc ggtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 94
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 94
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Ala Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 95
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 95
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtgggg ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 96
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 96
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Gly Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 97
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 97
atgccaacac tgcccagaac atttgacgac atttggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagtt gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggatcggagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgaac 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgccg gtcgatgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcattgg ccaccggcgg ggagtttgcc 720
gatgaaaatc ggatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 98
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 98
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Trp Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Leu Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Arg Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Asn Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Arg Ser Met Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Leu Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Arg Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 99
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 99
atgccaacac tgcccagaac atttgacgac attaggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gatgattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
ttgacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggatcggagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gtagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggctctgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggcaggg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccggt 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 100
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 100
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Arg Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Met Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Leu Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Arg Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Val Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Ser Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Arg Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Gly
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 101
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 101
atgccaacac tgcccagaac atttgacgac attaggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggatcggagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gtagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccggt 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 102
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 102
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Arg Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Arg Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Val Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Gly
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 103
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 103
atgccaacac tgcccagaac atttgacgac attacgtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gatgattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttatacca gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggatcggagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
acggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt tgggcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgagg gcacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 104
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 104
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Thr Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Met Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Gln Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Arg Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Thr Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Trp Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Gly His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 105
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 105
atgccaacac tgcccagaac atttgacgac attaggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gatgattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
ttgacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
acggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt tacgcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgagg gcacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 106
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 106
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Arg Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Met Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Leu Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Thr Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Tyr Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Gly His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 107
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 107
atgccaacac tgcccagaac atttgacgac atttggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gatgattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggatcggagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt tacgcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatc ggatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 108
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 108
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Trp Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Met Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Arg Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Tyr Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Arg Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 109
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 109
atgccaacac tgcccagaac atttgacgac atttggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gacgattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgagg gcacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccggt 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 110
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 110
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Trp Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Thr Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Gly His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Gly
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 111
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 111
atgccaacac tgcccagaac atttgacgac attaggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
acggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt tacgcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggcaggg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
attgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 112
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 112
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Arg Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Thr Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Tyr Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Arg Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Ile Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 113
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 113
atgccaacac tgcccagaac atttgacgac attacgtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gatgattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg gcggaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gtagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgagg gcacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 114
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 114
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Thr Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Met Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Ala Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Val Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Gly His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 115
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 115
atgccaacac tgcccagaac atttgacgac attacgtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gatgattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
ttgacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgaac 420
gtggaaatgt tcatagcgat ggataggccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 116
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 116
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Thr Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Met Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Leu Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Asn Val Glu Met Phe
130 135 140
Ile Ala Met Asp Arg Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 117
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 117
atgccaacac tgcccagaac atttgacgac atttggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gacgattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttatacca gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggatcggagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcgatgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt tacgcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccg ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgagg gcacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccggt 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 118
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 118
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Trp Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Thr Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Gln Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Arg Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Met Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Tyr Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Gly Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Gly His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Gly
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 119
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 119
atgccaacac tgcccagaac atttgacgac atttggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gacgattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccg ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggctctgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgagg gcacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg atgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 120
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 120
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Trp Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Thr Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Gly Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Ser Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Gly His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Met Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 121
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 121
atgccaacac tgcccagaac atttgacgac atttggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gacgattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccg ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggctctgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgagg gcacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccggt 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 122
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 122
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Trp Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Thr Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Gly Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Ser Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Gly His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Gly
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 123
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 123
atgccaacac tgcccagaac atttgacgac atttggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gacgattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggctctgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgagg gcacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg atgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccggt 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 124
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 124
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Trp Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Thr Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Ser Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Gly His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Met Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Gly
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 125
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 125
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga gctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccga acgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgtgggac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcgc ggtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc ttcctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tcacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 126
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 126
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Glu Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asn
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Trp Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Ala Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Phe Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Ile
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 127
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 127
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga gctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccga acgctccgtc gtacgaaatc gccgtgcact tagatccgcg gagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 128
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 128
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Glu Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asn
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Arg Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 129
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 129
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatggt gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tcacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 130
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 130
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Gly Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Ile
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 131
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 131
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga gctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg cagcattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cttgtctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgtgggac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcgc ggtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc ttcctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tcacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 132
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 132
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Glu Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Gln His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Leu Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Trp Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Ala Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Phe Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Ile
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 133
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 133
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga gctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg cagcattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cttgtctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcgc ggtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc ttcctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 134
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 134
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Glu Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Gln His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Leu Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Ala Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Phe Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 135
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 135
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga gctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccga acgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatggt gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tcacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 136
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 136
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Glu Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asn
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Gly Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Ile
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 137
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 137
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga gctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgcg gagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatggt gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tcacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 138
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 138
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Glu Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Arg Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Gly Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Ile
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 139
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 139
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgtg gagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcgc ggtagccgtt 2280
ctggatggcg aggttgatca ccgtgatggt gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 140
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 140
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Trp Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Ala Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Gly Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 141
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 141
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgcg gagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcgc ggtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc ttcctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 142
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 142
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Arg Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Ala Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Phe Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 143
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 143
atgccaacac tgcccagaac atttgacgac attcagtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggataagagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcggtgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcgc ggtagccgtt 2280
ctggatggcg aggttgatca ccgtgatggt gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 144
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 144
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Gln Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Lys Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Val Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Ala Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Gly Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 145
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 145
atgccaacac tgcccagaac atttgacgac atttggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagtt gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggatcggagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgaac 420
acggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgccg gtcgatgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt tacgcattgg ccaccggcgg ggagtttgcc 720
gatgaaaatc ggatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgagg gcacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 146
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 146
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Trp Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Leu Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Arg Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Asn Thr Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Arg Ser Met Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Tyr Ala Leu Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Arg Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Gly His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 147
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 147
atgccaacac tgcccagaac atttgacgac atttggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagtt gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggatcggagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgaac 420
acggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgccg gtcgatgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt tacgcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatc ggatgtttga cgacgcggca gacatggccg ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 148
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 148
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Trp Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Leu Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Arg Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Asn Thr Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Arg Ser Met Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Tyr Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Arg Met Phe Asp Asp Ala Ala Asp Met Ala Gly Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 149
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 149
atgccaacac tgcccagaac atttgacgac atttggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagtt gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggatcggagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgaac 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgccg gtcgatgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt tacgcattgg ccaccggcgg ggagtttgcc 720
gatgaaaatc ggatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgagg gcacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg atgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcgc ggtagccgtt 2280
ctggatggcg aggttgatca ccgtgatggt gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tcacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 150
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 150
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Trp Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Leu Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Arg Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Asn Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Arg Ser Met Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Tyr Ala Leu Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Arg Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Gly His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Met Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Ala Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Gly Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Ile
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 151
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 151
atgccaacac tgcccagaac atttgacgac atttggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagtt gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggatcggagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgaac 420
acggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgccg gtcgatgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt tacgcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 152
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 152
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Trp Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Leu Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Arg Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Asn Thr Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Arg Ser Met Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Tyr Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 153
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 153
atgccaacac tgcccagaac atttgacgac atttggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagtt gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggatcggagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgaac 420
acggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgccg gtcgatgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt tacgcattgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg atgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgtg gagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcttggag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatggt gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 154
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 154
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Trp Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Leu Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Arg Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Asn Thr Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Arg Ser Met Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Tyr Ala Leu Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Met Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Trp Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Leu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Gly Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 155
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 155
atgccaacac tgcccagaac atttgacgac atttggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gatgattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
ttgacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggatcggagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgaac 420
acggaaatgt tcatagcgat ggatgggccg aaacacgatg tgcagcgccg gtcgatgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt tacgcattgg ccaccggcgg ggagtttgcc 720
gatgaaaatc ggatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 156
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 156
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Trp Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Met Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Leu Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Arg Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Asn Thr Glu Met Phe
130 135 140
Ile Ala Met Asp Gly Pro Lys His Asp Val Gln Arg Arg Ser Met Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Tyr Ala Leu Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Arg Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 157
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 157
atgccaacac tgcccagaac atttgacgac atttggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagtt gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggatcggagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgaac 420
acggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcgatgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt tacgcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcgc ggtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tcacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 158
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 158
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Trp Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Leu Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Arg Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Asn Thr Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Met Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Tyr Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Ala Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Ile
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 159
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 159
atgccaacac tgcccagaac atttgacgac atttggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagtt gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggatcggagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgaac 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgccg gtcgatgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt tacgcattgg ccaccggcgg ggagtttgcc 720
gatgaaaatc ggatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgagg gcacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg cagcattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccacg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcgc ggtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tcacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 160
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 160
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Trp Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Leu Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Arg Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Asn Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Arg Ser Met Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Tyr Ala Leu Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Arg Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Gly His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Gln His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp His Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Ala Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Ile
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 161
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 161
atgccaacac tgcccagaac atttgacgac atttggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagtt gatgattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
ttgacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggatcggagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
acggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgccg gtcgatgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt tacgcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatc ggatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gacgagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 162
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 162
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Trp Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Leu Met Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Leu Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Arg Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Thr Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Arg Ser Met Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Tyr Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Arg Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Asp Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 163
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 163
atgccaacac tgcccagaac atttgacgac atttggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagtt gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggatcggagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgaac 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgccg gtcgatgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt tacgcatcgg ccaccggcgg ggagtttgcc 720
gatgaaaatc ggatgtttga cgacgcggca gacatggccg ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgtg gagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 164
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 164
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Trp Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Leu Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Arg Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Asn Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Arg Ser Met Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Tyr Ala Ser Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Arg Met Phe Asp Asp Ala Ala Asp Met Ala Gly Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Trp Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 165
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 165
atgccaacac tgcccagaac atttgacgac atttggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagtt gatgattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggatcggagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
acggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgccg gtcgatgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt tacgcattgg ccaccggcgg ggagtttgcc 720
gatgaaaatc ggatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 166
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 166
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Trp Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Leu Met Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Arg Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Thr Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Arg Ser Met Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Tyr Ala Leu Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Arg Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 167
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 167
atgccaacac tgcccagaac atttgacgac atttggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gatgattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggatcggagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgaac 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgccg gtcgatgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcattgg ccaccggcgg ggagtttgcc 720
gatgaaaatc ggatgtttga cgacgcggca gacatggccg ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgagg gcacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 168
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 168
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Trp Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Met Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Arg Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Asn Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Arg Ser Met Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Leu Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Arg Met Phe Asp Asp Ala Ala Asp Met Ala Gly Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Gly His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 169
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 169
atgccaacac tgcccagaac atttgacgac atttggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagtt gcaaattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg gcggaagaca tcctgttcgt ggatcggagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
acggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgccg gtcgatgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt tacgcattgg ccaccggcgg ggagtttgcc 720
gatgaaaatc ggatgtttga cgacgcggca gacatggccg ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 170
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 170
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Trp Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Leu Gln Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Ala Glu
100 105 110
Asp Ile Leu Phe Val Asp Arg Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Thr Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Arg Ser Met Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Tyr Ala Leu Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Arg Met Phe Asp Asp Ala Ala Asp Met Ala Gly Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 171
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 171
atgccaacac tgcccagaac atttgacgac atttggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gatgattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggatcggagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgaac 420
gtggaaatgt tcatagcgat ggatgggccg aaacacgatg tgcagcgccg gtcgatgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt tacgcattgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgagg gcacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 172
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 172
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Trp Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Met Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Arg Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Asn Val Glu Met Phe
130 135 140
Ile Ala Met Asp Gly Pro Lys His Asp Val Gln Arg Arg Ser Met Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Tyr Ala Leu Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Gly His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 173
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 173
atgccaacac tgcccagaac atttgacgac atttggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagtt gatgattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggatcggagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgaac 420
gtggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgccg gtcgatgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt gcagcattgg ccaccggcgg ggagtttgcc 720
gatgaaaatc ggatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgagg gcacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 174
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 174
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Ile Trp Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Leu Met Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Arg Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Asn Val Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Arg Ser Met Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Ala Ala Leu Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Arg Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Gly His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 175
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 175
atgccaacac tgcccagaac atttgactac ttgtggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gatgattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggatcggagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
acggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgcag ctcgatgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt tacgcattgg ccaccggcgg ggagtttgcc 720
gatgaaaatc ggatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgagg gcacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 176
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 176
Met Pro Thr Leu Pro Arg Thr Phe Asp Tyr Leu Trp Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Met Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Arg Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Thr Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Ser Ser Met Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Tyr Ala Leu Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Arg Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Gly His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 177
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 177
atgccaacac tgcccagaac atttgacgac ttgtggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagtt gatgattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggatcggagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
acggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgccg gtcgatgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctac tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt tacgcattgg ccaccggcgg ggagtttgcc 720
gatgaaaatc ggatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgagg gcacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaagg ggtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 178
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 178
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Leu Trp Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Leu Met Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Arg Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Thr Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Arg Ser Met Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Thr Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Tyr Ala Leu Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Arg Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Gly His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Gly Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 179
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 179
atgccaacac tgcccagaac atttgacgac ttgtggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagag gatgattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggatcggagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
acggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgccg gtcgatgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctac tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt tacgcattgg ccaccggcgg ggagtttgcc 720
gatgaaaatc ggatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgagg gcacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 180
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 180
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Leu Trp Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Arg Met Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Arg Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Thr Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Arg Ser Met Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Thr Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Tyr Ala Leu Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Arg Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Gly His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 181
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 181
atgccaacac tgcccagaac atttgacgac ttgtggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagtt gatgattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggatcggagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
acggaaatgt tcatagcgat ggatgggccg aaacacgatg tgcagcgccg gtcgatgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt tacgcattgg ccaccggcgg ggagtttgcc 720
gatgaaaatg ccatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgagg gcacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 182
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 182
Met Pro Thr Leu Pro Arg Thr Phe Asp Asp Leu Trp Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Leu Met Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Arg Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Thr Glu Met Phe
130 135 140
Ile Ala Met Asp Gly Pro Lys His Asp Val Gln Arg Arg Ser Met Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Tyr Ala Leu Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Ala Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Gly His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795
<210> 183
<211> 2400
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多核苷酸”
<400> 183
atgccaacac tgcccagaac atttgactac ttgtggtccc gactgattaa cgccacctcc 60
agggtggtgc cgatgcagtt gatgattcag ggactgaaat tcttaatgag cgccaagagg 120
aagaccttcg gcccacgccg accgatgccc gaattcgttg aaacacccat cccggacgtt 180
aacacgctgg cccttgagga catcgatgtc agcaatccgt ttttataccg gcagggtcag 240
tggcgcgcct atttcaaacg gttgcgtgat gaggcgccgg tccattacca gaagaacagc 300
cctttcggcc ccttctggtc ggtaactcgg tttgaagaca tcctgttcgt ggatcggagt 360
cacgacctgt tttccgccga gccgcaaatc attctcggtg accctccgga ggggctgtcg 420
acggaaatgt tcatagcgat ggatccgccg aaacacgatg tgcagcgccg gtcgatgcag 480
ggagtagtgg caccgaaaaa cctgaaggag atggaggggc tgatccgatc acgcaccggc 540
gatgtgcttg acagcctgcc tacagacaaa ccctttaact gggtacctgc tgtttccaag 600
gaactcacag gccgcatgct ggcgacgctt ctggattttc cttacgagga acgccacaag 660
ctggttgagt ggtcggacag aatggcaggt tacgcattgg ccaccggcgg ggagtttgcc 720
gatgaaaatc ggatgtttga cgacgcggca gacatggccc ggtctttctc caggctttgg 780
cgggacaagg aggcgcgccg cgcagcaggc gaggagcccg gtttcgattt gatcagcctg 840
ttgcagagca acaaagaaac gaaagacctg atcaatcggc cgatggagtt tatcggtaat 900
ttgacgctgc tcatagtcgc cggcaacgat acgacgcgca actcgatgag tggtggcctg 960
gtggccatga acgaattccc cagggaattt gaaaaattga aggcaaaacc ggagttgatt 1020
ccgaacatgg tgtcggaaat catccgctgg caaacgccgc tggcctatat gcgccgaatc 1080
gccaagcagg atgtcgaact gggcggccag accatcaaga agggtgatcg agttgtcatg 1140
tggtacgcgt cgggtaaccg ggacgagcgc aaatttgaca accccgatca gttcatcatt 1200
gatcgcaagg acgcacgaaa ccacatgtcg ttcggctatg gggttcaccg ttgcatgggc 1260
aaccgtctgg ctgaactgca actgcgcatc ctctgggaag aaatactcaa gcgttttgac 1320
aacatcgaag tcgtcgaaga gcccgagcgg gtgcagtcca acttcgtgcg gggctattcc 1380
aggttgatgg tcaaactgac accgaacagt gtactccatc gtcatcaacc tgtcaccatc 1440
ggcgagccgg ccgctcgtgc tgtgagccgc acggtgaccg ttgagcgtct tgatcgcatt 1500
gccgacgatg tccttcgcct ggtccttcgc gatgctggag gtaaaaccct cccgacgtgg 1560
acgcctggcg ctcacatcga cctggatctg ggtgctctga gccgtcagta ttcgctctgc 1620
ggcgctccgg atgctccgtc gtacgaaatc gccgtgcact tagatccgga aagccgtggt 1680
ggaagccgct atattcatga acagctggaa gttggaagtc cgctgcgtat gcgtggccca 1740
cgcaaccatt tcgccctgga tccgggtgcg gaacattacg tgtttgttgc cgggggtatc 1800
ggcatcacgc cggtgctggc aatggcggat catgcccgtg cgcgtggttg gtcgtacgaa 1860
ctgcattatt gtggtcgtaa tcgtagcggt atggcttacc tggaacgcgt cgcgggacat 1920
ggtgaccgcg ctgccttgca cgtatctgaa gaaggcaccc gcattgatct ggcggcatta 1980
cttgctgaac cggcgccggg cgtgcaaatc tacgcctgcg gtccgggccg tttattagcg 2040
ggtcttgaag acgcgtctcg taattggccg gatggcgcgc ttcatgtgga gcatttcact 2100
tcgagtttag ccgctttgga tccggatgtc gaacatgcct ttgatttgga gctgcgtgac 2160
tctggcctta ccgttcgcgt cgagccaact cagaccgttt tagacgcttt gcgtgcgaac 2220
aatatcgacg tcccgtcgga ttgcgaagag gggctgtgtg gttcttgcga agtagccgtt 2280
ctggatggcg aggttgatca ccgtgatacc gttctgacta aggccgagcg cgccgcgaat 2340
cgtcagatga tgacttgctg cagtcgtgca tgcggtgatc gtctggtcct gcgcctctaa 2400
<210> 184
<211> 799
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注意=“人工序列的描述:合成多肽”
<400> 184
Met Pro Thr Leu Pro Arg Thr Phe Asp Tyr Leu Trp Ser Arg Leu Ile
1 5 10 15
Asn Ala Thr Ser Arg Val Val Pro Met Gln Leu Met Ile Gln Gly Leu
20 25 30
Lys Phe Leu Met Ser Ala Lys Arg Lys Thr Phe Gly Pro Arg Arg Pro
35 40 45
Met Pro Glu Phe Val Glu Thr Pro Ile Pro Asp Val Asn Thr Leu Ala
50 55 60
Leu Glu Asp Ile Asp Val Ser Asn Pro Phe Leu Tyr Arg Gln Gly Gln
65 70 75 80
Trp Arg Ala Tyr Phe Lys Arg Leu Arg Asp Glu Ala Pro Val His Tyr
85 90 95
Gln Lys Asn Ser Pro Phe Gly Pro Phe Trp Ser Val Thr Arg Phe Glu
100 105 110
Asp Ile Leu Phe Val Asp Arg Ser His Asp Leu Phe Ser Ala Glu Pro
115 120 125
Gln Ile Ile Leu Gly Asp Pro Pro Glu Gly Leu Ser Thr Glu Met Phe
130 135 140
Ile Ala Met Asp Pro Pro Lys His Asp Val Gln Arg Arg Ser Met Gln
145 150 155 160
Gly Val Val Ala Pro Lys Asn Leu Lys Glu Met Glu Gly Leu Ile Arg
165 170 175
Ser Arg Thr Gly Asp Val Leu Asp Ser Leu Pro Thr Asp Lys Pro Phe
180 185 190
Asn Trp Val Pro Ala Val Ser Lys Glu Leu Thr Gly Arg Met Leu Ala
195 200 205
Thr Leu Leu Asp Phe Pro Tyr Glu Glu Arg His Lys Leu Val Glu Trp
210 215 220
Ser Asp Arg Met Ala Gly Tyr Ala Leu Ala Thr Gly Gly Glu Phe Ala
225 230 235 240
Asp Glu Asn Arg Met Phe Asp Asp Ala Ala Asp Met Ala Arg Ser Phe
245 250 255
Ser Arg Leu Trp Arg Asp Lys Glu Ala Arg Arg Ala Ala Gly Glu Glu
260 265 270
Pro Gly Phe Asp Leu Ile Ser Leu Leu Gln Ser Asn Lys Glu Thr Lys
275 280 285
Asp Leu Ile Asn Arg Pro Met Glu Phe Ile Gly Asn Leu Thr Leu Leu
290 295 300
Ile Val Ala Gly Asn Asp Thr Thr Arg Asn Ser Met Ser Gly Gly Leu
305 310 315 320
Val Ala Met Asn Glu Phe Pro Arg Glu Phe Glu Lys Leu Lys Ala Lys
325 330 335
Pro Glu Leu Ile Pro Asn Met Val Ser Glu Ile Ile Arg Trp Gln Thr
340 345 350
Pro Leu Ala Tyr Met Arg Arg Ile Ala Lys Gln Asp Val Glu Leu Gly
355 360 365
Gly Gln Thr Ile Lys Lys Gly Asp Arg Val Val Met Trp Tyr Ala Ser
370 375 380
Gly Asn Arg Asp Glu Arg Lys Phe Asp Asn Pro Asp Gln Phe Ile Ile
385 390 395 400
Asp Arg Lys Asp Ala Arg Asn His Met Ser Phe Gly Tyr Gly Val His
405 410 415
Arg Cys Met Gly Asn Arg Leu Ala Glu Leu Gln Leu Arg Ile Leu Trp
420 425 430
Glu Glu Ile Leu Lys Arg Phe Asp Asn Ile Glu Val Val Glu Glu Pro
435 440 445
Glu Arg Val Gln Ser Asn Phe Val Arg Gly Tyr Ser Arg Leu Met Val
450 455 460
Lys Leu Thr Pro Asn Ser Val Leu His Arg His Gln Pro Val Thr Ile
465 470 475 480
Gly Glu Pro Ala Ala Arg Ala Val Ser Arg Thr Val Thr Val Glu Arg
485 490 495
Leu Asp Arg Ile Ala Asp Asp Val Leu Arg Leu Val Leu Arg Asp Ala
500 505 510
Gly Gly Lys Thr Leu Pro Thr Trp Thr Pro Gly Ala His Ile Asp Leu
515 520 525
Asp Leu Gly Ala Leu Ser Arg Gln Tyr Ser Leu Cys Gly Ala Pro Asp
530 535 540
Ala Pro Ser Tyr Glu Ile Ala Val His Leu Asp Pro Glu Ser Arg Gly
545 550 555 560
Gly Ser Arg Tyr Ile His Glu Gln Leu Glu Val Gly Ser Pro Leu Arg
565 570 575
Met Arg Gly Pro Arg Asn His Phe Ala Leu Asp Pro Gly Ala Glu His
580 585 590
Tyr Val Phe Val Ala Gly Gly Ile Gly Ile Thr Pro Val Leu Ala Met
595 600 605
Ala Asp His Ala Arg Ala Arg Gly Trp Ser Tyr Glu Leu His Tyr Cys
610 615 620
Gly Arg Asn Arg Ser Gly Met Ala Tyr Leu Glu Arg Val Ala Gly His
625 630 635 640
Gly Asp Arg Ala Ala Leu His Val Ser Glu Glu Gly Thr Arg Ile Asp
645 650 655
Leu Ala Ala Leu Leu Ala Glu Pro Ala Pro Gly Val Gln Ile Tyr Ala
660 665 670
Cys Gly Pro Gly Arg Leu Leu Ala Gly Leu Glu Asp Ala Ser Arg Asn
675 680 685
Trp Pro Asp Gly Ala Leu His Val Glu His Phe Thr Ser Ser Leu Ala
690 695 700
Ala Leu Asp Pro Asp Val Glu His Ala Phe Asp Leu Glu Leu Arg Asp
705 710 715 720
Ser Gly Leu Thr Val Arg Val Glu Pro Thr Gln Thr Val Leu Asp Ala
725 730 735
Leu Arg Ala Asn Asn Ile Asp Val Pro Ser Asp Cys Glu Glu Gly Leu
740 745 750
Cys Gly Ser Cys Glu Val Ala Val Leu Asp Gly Glu Val Asp His Arg
755 760 765
Asp Thr Val Leu Thr Lys Ala Glu Arg Ala Ala Asn Arg Gln Met Met
770 775 780
Thr Cys Cys Ser Arg Ala Cys Gly Asp Arg Leu Val Leu Arg Leu
785 790 795

Claims (13)

1.一种CYP153A-还原酶杂合融合多肽变体,其包含与氨基酸序列SEQ ID NO:38的至少90%序列同一性,其中所述CYP153A-还原酶杂合融合多肽变体包含在氨基酸位置12处的突变和在以下氨基酸位置中的每一者处的突变
(a)SEQ ID NO:38的12、27、28、119、141、157、159、231、233和244;
(b)SEQ ID NO:38的12、28、119、140、157、159、233、244、254和407;
(c)SEQ ID NO:38的12、27、111、119、141、157、159、231、233、244和254;
(d)SEQ ID NO:38的12、28、119、140、149、157、159、231、233和407;
(e)SEQ ID NO:38的12、27、28、119、140、157、159、233、244和407;
(f)SEQ ID NO:38的10、11、12、28、119、141、159、231、233、244和407;
(g)SEQ ID NO:38的11、12、27、28、119、141、157、159、197、231、233、244、407和477;
(h)SEQ ID NO:38的11、12、28、119、141、157、159、197、231、233、244和407;或
(i)SEQ ID NO:38的11、12、27、28、119、141、149、157、159、231、233和407;
其中所述CYP153A-还原酶杂合融合多肽变体催化脂肪酸转化为ω-羟基化脂肪酸。
2.如权利要求1所述的CYP153A-还原酶杂合融合多肽变体,其中:
(a)在氨基酸位置SEQ ID NO:38的12、27、28、119、141、157、159、231、233和244处的所述突变分别为Q12W、R27L、Q28M、K119R、V141T、S157R、V159M、A231Y、S233L和A244R;
(b)在氨基酸位置SEQ ID NO:38的12、28、119、140、157、159、233、244、254和407处的所述突变分别为Q12W、Q28M、K119R、S140N、S157R、V159M、S233L、A244R、R254G和N407G;
(c)在氨基酸位置SEQ ID NO:38的12、27、111、119、141、157、159、231、233、244和254处的所述突变分别为Q12W、R27L、F111A、K119R、V141T、S157R、V159M、A231Y、S233L、A244R和R254G;
(d)在氨基酸位置SEQ ID NO:38的12、28、119、140、149、157、159、231、233和407处的所述突变分别为Q12W、Q28M、K119R、S140N、P149G、S157R、V159M、A231Y、S233L和N407G;
(e)在氨基酸位置SEQ ID NO:38的12、27、28、119、140、157、159、233、244和407处的所述突变分别为Q12W、R27L、Q28M、K119R、S140N、S157R、V159M、S233L、A244R和N407G;
(f)在氨基酸位置SEQ ID NO:38的10、11、12、28、119、141、159、231、233、244和407处的所述突变分别为D10Y、I11L、Q12W、Q28M、K119R、V141T、V159M、A231Y、S233L、A244R和N407G;
(g)在氨基酸位置SEQ ID NO:38的11、12、27、28、119、141、157、159、197、231、233、244、407和477处的所述突变分别为I11L、Q12W、R27L、Q28M、K119R、V141T、S157R、V159M、A197T、A231Y、S233L、A244R、N407G和P477G;
(h)在氨基酸位置SEQ ID NO:38的11、12、28、119、141、157、159、197、231、233、244和407处的所述突变分别为I11L、Q12W、Q28M、K119R、V141T、S157R、V159M、A197T、A231Y、S233L、A244R和N407G;和
(i)在氨基酸位置SEQ ID NO:38的11、12、27、28、119、141、149、157、159、231、233和407处的所述突变分别为I11L、Q12W、R27L、Q28M、K119R、V141T、P149G、S157R、V159M、A231Y、S233L和N407G。
3.如权利要求2所述的CYP153A-还原酶杂合融合多肽变体,其中:
(a)(a)的所述CYP153A-还原酶杂合融合多肽变体包含氨基酸序列SEQ ID NO:166;
(b)(b)的所述CYP153A-还原酶杂合融合多肽变体包含氨基酸序列SEQ ID NO:168;
(c)(c)的所述CYP153A-还原酶杂合融合多肽变体包含氨基酸序列SEQ ID NO:170;
(d)(d)的所述CYP153A-还原酶杂合融合多肽变体包含氨基酸序列SEQ ID NO:172;
(e)(e)的所述CYP153A-还原酶杂合融合多肽变体包含氨基酸序列SEQ ID NO:174;
(f)(f)的所述CYP153A-还原酶杂合融合多肽变体包含氨基酸序列SEQ ID NO:176;
(g)(g)的所述CYP153A-还原酶杂合融合多肽变体包含氨基酸序列SEQ ID NO:178;
(h)(h)的所述CYP153A-还原酶杂合融合多肽变体包含氨基酸序列SEQ ID NO:180;以及
(i)(i)的所述CYP153A-还原酶杂合融合多肽变体包含氨基酸序列SEQ ID NO:182。
4.一种CYP153A-还原酶杂合融合多肽变体,其选自由SEQ ID NO:166、SEQ ID NO:168、SEQ ID NO:170、SEQ ID NO:172、SEQ ID NO:174、SEQ ID NO:176、SEQ ID NO:178、SEQ IDNO:180和SEQ ID NO:182组成的组。
5.如权利要求1至4中任一项所述的CYP153A-还原酶杂合融合多肽变体,其中如与通过CYP153A-还原酶杂合融合多肽SEQ ID NO:6或SEQ ID NO:38在相应宿主细胞中的表达产生的ω-羟基化脂肪酸的效价相比,所述CYP153A-还原酶杂合融合多肽变体在重组宿主细胞中的表达引起ω-羟基化脂肪酸的较高效价。
6.如权利要求1至4中任一项所述的CYP153A-还原酶杂合融合多肽变体,其中所述CYP153A-还原酶杂合融合多肽变体是杂合CYP153A-RedRhF融合蛋白变体。
7.一种重组宿主细胞,其表达如权利要求1至4中任一项所述的CYP153A-还原酶杂合融合多肽变体。
8.如权利要求7所述的重组宿主细胞,其进一步表达EC 3.1.2.-、EC 3.1.1.5或EC3.1.2.14的硫酯酶多肽。
9.如权利要求8所述的重组宿主细胞,其中所述重组宿主细胞当在含有碳源的培养基中培养时产生ω-羟基化脂肪酸组合物,所述ω-羟基化脂肪酸组合物具有比由表达包含SEQ ID NO:38或SEQ ID NO:6的相应CYP153A-还原酶杂合融合多肽的宿主细胞产生的ω-羟基化脂肪酸组合物的效价大至少10%、大至少15%、大至少20%、大至少25%或大至少30%的效价。
10.一种细胞培养物,其包含如权利要求7至9中任一项所述的重组宿主细胞。
11.一种产生ω-羟基化脂肪酸的方法,所述方法包括:
(i)在碳源存在下培养如权利要求7至9中任一项所述的重组宿主细胞,或根据权利要求10所述的细胞培养物;和
(ii)收集ω-羟基化脂肪酸。
12.一种重组微生物,其包含经过工程改造以表达编码多肽的至少两个核酸序列的途径,所述多肽包括:
(i)EC 3.1.2.-、EC 3.1.1.5或EC 3.1.2.14的硫酯酶;和
(ii)如权利要求1至6中任一项所述的CYP153A-还原酶杂合融合多肽变体。
13.如权利要求1至6中任一项所述的CYP153A-还原酶杂合融合多肽变体,或如权利要求7至9中任一项所述的重组宿主细胞,或根据权利要求10所述的细胞培养物,或根据权利要求11所述的方法,或根据权利要求12所述的重组微生物,其中所述CYP153A-还原酶杂合融合多肽变体是自给自足的CYP153A-RedRhF杂合融合多肽变体。
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